PMID- 7770443 TI - Confidentiality of HIV medical records. PMID- 7770444 TI - Pediatric tachycardias. PMID- 7770445 TI - Hospitals with strong nursing practice have better patient outcomes. PMID- 7770446 TI - DNA recognition by a beta-sheet. AB - DNA recognition by a beta-sheet is discussed in the light of crystal structures of the MetJ and Arc repressors. The DNA binding geometry of a beta-sheet can be understood in terms of (i) close fitting of the two surfaces and (ii) matching of residue and base positions. A beta-sheet is not entirely flat but has a curvature. A beta-sheet of the Met-Arc family faces the DNA major groove with its convex surface; the local DNA major groove is deepest at the centre. The beta sheet follows 6 bp; every two residues face the DNA and the first and fifth residues, which are separated by 13.2 A, bind, respectively, to the third and sixth bases, which are separated by 13.5 A, on the same DNA strand. PMID- 7770447 TI - Greek key jellyroll protein motif design: expression and characterization of a first-generation molecule. AB - A protein designed de novo to fold into the Greek key jellyroll structural motif has been studied. Theoretical analyses have indicated that the designed sequence should adopt the beta-strand arrangement of the Greek key jellyroll rather than any other arrangement. A synthetic gene was constructed and the protein expressed in Escherichia coli. Circular dichroism spectroscopy is consistent with the protein folding into the designed conformation and also suggests the presence of tertiary structure. Fluorescence spectroscopy showed the single tryptophan to be partially buried, while denaturation studies showed changes in fluorescence to precede alterations in secondary structure. PMID- 7770448 TI - Increasing thermal stability of subtilisin from mutations suggested by strongly interacting side-chain clusters. AB - In this paper we present for seven subtilisin structures a systematic comparison of densely packed side-group clusters (defined as an ensemble of side chains with extensive internal atomic contacts as compared with those made with the surrounding protein environment and measured relative to the maximum possible for each residue type). Spatially consistent clusters are observed at structurally equivalent positions in the proteins, as revealed by careful multiple superpositioning of the respective backbone atoms. The clusters are positioned at strategic loop-connecting sites near the protein surfaces. The residues within consistent clusters displaying extensive association show varying conservation at structurally equivalent alignment sites. Suggestions for residue substitutions, as observed over the seven tertiary structures, were taken from the cluster positions and were shown to be consistent with a number of point mutations in one of the seven structures (savinase) that result in increased thermal stability. PMID- 7770449 TI - Replacing the glutamate ligand in the structural zinc site of Sulfolobus solfataricus alcohol dehydrogenase with a cysteine decreases thermostability. AB - The alcohol dehydrogenase gene from the thermophilic archaeum Sulfolobus solfataricus has been subcloned and expressed in Escherichia coli under the control of the T7 inducible promoter. The recombinant protein shows properties analogous to those of the native enzyme, including thermostability, despite the fact that E.coli does not post-translationally modify two lysine residues which are N-epsilon-methylated in the native enzyme. We constructed a 3-D model of the S.solfataricus alcohol dehydrogenase using the known structure of its isozyme from horse liver as a template. Our analysis of the structural zinc binding site suggested that this site is present and functional in the S.solfataricus enzyme and that a glutamate ligand can contribute to thermostability by influencing electrostatic interactions around the metal centre. To investigate this hypothesis, we constructed, expressed and characterized a mutant where the glutamate is replaced by a cysteine, thus restoring the zinc binding site of mesophilic alcohol dehydrogenases. The mutant shows the same activity but a reduced thermostability with respect to the wild-type recombinant protein, as suggested by our model. PMID- 7770450 TI - Thermal stability of chimeric isopropylmalate dehydrogenase genes constructed from a thermophile and a mesophile. AB - Chimeric isopropylmalate dehydrogenases were constructed by connecting the genes isolated from an extreme thermophile, Thermus thermophilus, and a mesophile, Bacillus subtilis. These genes were expressed in Escherichia coli. The enzymes were purified and analysed. Enzymes of T.thermophilus and B.subtilis and chimeric enzymes showed similar enzymological characteristics except for thermal stability. The stability of each enzyme was approximately proportional to the content of the amino acid sequence from the T.thermophilus enzyme. The results suggested that amino acid residues contributing the thermal stability distribute themselves, in general, evenly at least in the N-terminal half of the amino acid sequence of T.thermophilus isopropylmalate dehydrogenase. PMID- 7770451 TI - Highly effective protease inhibitors from variants of human pancreatic secretory trypsin inhibitor (hPSTI): an assessment of 3-D structure-based protein design. AB - The results of a protein design project are used to compare different predictive strategies with respect to protein-protein interactions. We have been able to generate variants of human pancreatic secretory trypsin inhibitor (hPSTI) optimized with respect to the affinity and specificity for human leukocyte elastase relative to trypsin and chymotrypsin, and in particular chymotrypsin. The extremely strong and specific human leukocyte elastase inhibitors were thus developed in three rounds of mutagenesis and two rounds of 3-D modelling; only 24 variants in total were synthesized, although variations at seven different amino acid positions were involved (i.e. from 20(7) possible variants). An excellent elastase inhibitor could be designed with the minimum of two amino acid exchanges. The value of structural modelling and actual structure determination is discussed in the light of the experimental results of the designed protein variants and the results of tertiary structure determinations of the free variant and the inhibitor-protease complex. Particular reference is given to the strategy to be followed in protein design projects in general and to the development of protease inhibitors in particular. PMID- 7770452 TI - L3 loop-mediated mechanisms of pore closing in porin: a molecular dynamics perturbation approach. AB - L3 loop-mediated mechanisms for pore closing in porin are investigated with molecular dynamics simulation, using an approach that can be related to the phenomenon of voltage gating. Voltage gating is seen as a perturbation of the electrostatic screening inside the porin pore where, by the influence of the potential gradient, water and counter-ion distribution can be slightly displaced from their equilibrium distribution. This is simulated by perturbing the screening electrostatics of ionizable groups inside the pore. Under these conditions, a localized conformational change takes place, involving 12 (Ile102 Ala113) out of the 44 residues of the loop. The pore is reduced to a sixth of its open state size. The conformational change can be achieved with a small perturbation and it is reversible once the perturbation is switched off (relaxation process). Other types of behaviour predominating at higher simulation temperatures are found for the loop, involving an extra conformational change in the Thr92-Asp96 loop segment. This conformational change completely closes the pore, but is not reversible under the simulation conditions. Both zones involved in the conformational changes contain or overlap the zones which were described previously, using other techniques, to be the most flexible zones of the loop. PMID- 7770453 TI - Modification of S1 subsite specificity in the cysteine protease cathepsin B. AB - Cysteine proteases of the papain family generally exhibit broad P1 specificity. A notable exception is papaya proteinase IV (PPIV), which only accepts Gly at this position. In all other cysteine proteases the S1 subsite residues 23 and 65 (papain numbering) are absolutely conserved as Gly, while in PPIV they are replaced by Glu and Arg, respectively. These differences appear to underlie both PPIV specificity and its resistance to inhibition by cystatins. To test this hypothesis, the equivalent residues (Gly27 and Gly73) in the mammalian cysteine protease cathepsin B were changed to Glu and Arg, respectively. Relative to the wild-type enzyme, the Gly27Glu and Gly73Arg mutants showed a drastic reduction in activity with substrates containing a P1 Arg. In contrast, substrates having a Gly residue in P1 were hydrolyzed effectively. The double mutant (Gly27Glu:Gly73Arg) exhibited no detectable activity against any substrate studied. Inhibition of the Gly73Arg mutant by E-64 [1-(L-trans-epoxysuccinyl-L leucylamino)-4-guanidinobutane] was found to be similar to that of the wild-type enzyme. In contrast, inhibition by cystatin C exhibited a 20,000-fold reduction. These results demonstrate the dramatic influence of side chains at sequence locations 27 and 73 on the S1 subsite specificity of cysteine proteases. PMID- 7770454 TI - Recombinant pro-regions from papain and papaya proteinase IV-are selective high affinity inhibitors of the mature papaya enzymes. AB - Proteolytic enzymes require the presence of their pro-regions for correct folding. Of the four proteolytic enzymes from Carica papaya, papain and papaya proteinase IV (PPIV) have 68% sequence identity. We find that their pro-regions are even more similar, exhibiting 73.6% identity. cDNAs encoding the pro-regions of these two proteinases have been expressed in Escherichia coli independently from their mature enzymes. The recombinant pro-regions of papain and PPIV have been shown to be high affinity inhibitors of all four of the mature native papaya cysteine proteinases. Their inhibition constants are in the range 10(-6) - 10(-9) M. PPIV was inhibited two to three orders of magnitude less effectively than papain, chymopapain and caricain. The pro-region of PPIV, however, inhibited its own mature enzyme more effectively than did the pro-region of papain. Alignment of the sequences of the four papaya enzymes shows that there is a highly variable section towards the C-terminal of the pro-region. This region may therefore confer selectivity to the pro-regions for the individual proteolytic enzymes. PMID- 7770455 TI - Interactions of (Ala*Ala*Lys*Pro)n and (Lys*Lys*Ser*Pro)n with DNA. Proposed coiled-coil structure of AlgR3 and AlgP from Pseudomonas aeruginosa. AB - The proteins, AlgR3 and AlgP, are involved in the regulation of alginate synthesis in Pseudomonas. They contain multiple repeats of Ala*Ala*Lys*Pro as do several other proteins that resemble histones. The interactions of synthesis oligopeptides composed of repeated Ala*Ala*Lys*Pro or Lys*Lys*Ser*Pro units with DNA were studied by fluorescence of the Fmoc (9-fluorenylmethyloxycarbonyl) group attached to the N-termini of the peptides. DNA quenching of the Fmoc fluorescence of the peptides was used to estimate the apparent association constants for the interaction of Fmoc(AAKP)nOH (n = 2, 4, 8, 18, 32) and of Fmoc (KKSP)nOH (n = 2, 4, 8, 16, 20, 32) with DNA. The Fmoc(AAKP)nOH peptides bind to DNA only at low ionic strength; the Fmoc(KKSP)n OH peptides interact with DNA at both low (0.05 M KCl) and high (0.2 M KCl) salt. At low ionic strength an increase in the number of the repeat units causes an increase in the apparent association constant up to approximately 2 x 10(6) M-1 for both types of peptides at N congruent to 24. The insertion of an AAKTA unit into the middle of the Fmoc(AAKP)8OH peptide increases its affinity to DNA. We propose a model of (AAKP)n and of its interaction with DNA. The repeat unit consists of a single turn of alpha-helix followed by a bend necessitated by Pro. The resultant coiled-coil forms a right-handed superhelix with 10 AAKPs per repeat distance of approximately 33 A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770456 TI - Progesterone binding to uteroglobin: two alternative orientations of the ligand. AB - Progesterone binding to a homodimer of uteroglobin takes place in a hydrophobic cavity formed by the two subunits. Previous mutational analyses have shown that the tyrosine (21 and 21') and threonine (60 and 60') residues of the uteroglobin dimer are directly involved in progesterone binding. To analyze the contribution of each of the two tyrosines and threonines in the dimer, we have constructed a covalently linked uteroglobin dimer (UGcl) by fusing two uteroglobin cDNAs via a synthetic linker sequence. Escherichia coli expressed UGcl bound progesterone with the same affinity as the native dimeric protein. Replacement of both tyrosines by phenylalanines abolished progesterone binding. Replacement of either the C-terminal tyrosine 21 or the N-terminal tyrosine 21' separately, reduced the affinity for progesterone 3- to 4-fold, suggesting that both tyrosines participate in progesterone binding. In contrast, substitutions of the threonine residues of the C- or N-terminal moities had no effect, whereas the replacement of both threonines reduced the affinity for progesterone 2- to 3-fold. These data, together with computer models, suggest that progesterone docks in the internal binding pocket of uteroglobin in two different orientations. PMID- 7770457 TI - Engineered turns of a recombinant antibody improve its in vivo folding. AB - Using recombinant antibodies functionally expressed by secretion to the periplasm in Escherichia coli as a model system, we identified mutations located in turns of the protein which reduce the formation of aggregates during in vivo folding or which influence cell stability during expression. Unexpectedly, the two effects are based on different mutations and could be separated, but both mutations act synergistically in vivo. Neither mutation increases the thermodynamic stability in vitro. However, the in vivo folding mutation correlates with the yield of oxidative folding in vitro, which is limited by the side reaction of aggregation. The in vivo folding data also correlate with the rate and activation entropy of thermally induced aggregation. This analysis shows that it is possible to engineer improved frameworks for semi-synthetic antibody libraries which may be important in maintaining library diversity. Moreover, limitations in recombinant protein expression can be overcome by single amino acid substitutions. PMID- 7770458 TI - Evidence against a potential endoplasmic reticulum transmembrane domain of 27K zein expressed in Xenopus oocytes. AB - During the cellular protein targeting process, zeins (maize storage proteins) are retained in the endoplasmic reticulum (ER) where they accumulate into protein bodies. There are circumstantial and preliminary data indicating that the 27K zein, a class of zein proteins, may span the ER membrane. This potential transmembrane domain is considered very significant with regard to the mechanism of ER retention for zeins. The potential transmembrane domain may permit the 27K zein to remain in the ER and to serve as an anchor for other classes of zein, thus acting as a nucleating factor for protein body formation. This study investigated the potential transmembrane feature in a heterologous system (Xenopus laevis oocyte). Following injection of synthetic 27K zein mRNA, isolated protein vesicles were subjected to proteinase K digestion, surface biotinylation and alkaline extraction. Throughout three categories of assay the possible role of the 27K zein as a transmembrane protein was consistently refuted in this study. The 27K zein polypeptide was affected by neither proteinase K digestion nor biotinylation and was released from alkali-stripped membranes. This study, therefore, concludes that the 27K zein is not a protein body nucleating factor by virtue of an ER transmembrane feature. PMID- 7770459 TI - Active oxygen intermediates--beneficial or deleterious? An introduction. PMID- 7770460 TI - Mechanisms of oxidant stress-induced acute tissue injury. AB - During the last 25 years, a large body of experimental evidence has accumulated from pharmacological intervention studies that suggests an important role for reactive oxygen species in numerous pathophysiological processes. While a variety of chemical mechanisms of reactive oxygen-induced damage to lipids, proteins, and DNA is fairly well understood, the molecular pathology of oxidant stress-induced tissue injury in vivo remains unclear in most cases. Recent advances indicate that the direct destructive potential of reactive oxygen in vivo is limited by the extensive detoxification capacity of most cells and may be restricted to a small fraction of cells exposed to a locally high oxidant stress. However, reactive oxygen species can participate in recruitment of inflammatory cells by upregulation of adhesion molecules and generation of chemotactic factors, and are necessary for protease-mediated cell injury in vivo. Reactive oxygen species can also scavenge other biologically active molecules (e.g., nitric oxide), thereby modulating indirectly their effector cells. In addition to the discussed effects relevant for acute injury, other oxidant stress-induced mechanisms (e.g., DNA modifications) may be relevant in chronic disease states. A solid mechanistic understanding of the role of reactive oxygen species in the overall pathophysiology is critical for providing a rationale for antioxidant therapy and the targeted development of new antioxidant drugs. PMID- 7770461 TI - Superoxide radical: controversies, contradictions, and paradoxes. AB - The study of free radical biology has engendered a great deal of controversy and apparently conflicting observations, particularly with regard to the use of the antioxidant enzyme superoxide dismutase as a protective or therapeutic agent. Slowly, the reasons behind the confusion are beginning to emerge. The superoxide radical, O2.-, has a number of paradoxical physiological and pathophysiological roles. Several examples of the radical's schizophrenic behavior include its roles in bactericidal action versus inflammation, as a modulator of cell division versus malignant transformation and apoptosis, and as both an initiator and a terminator of lipid peroxidation. PMID- 7770462 TI - Control of collagen deposition in mammalian lung. AB - This review considers the mechanisms controlling collagen deposition in mammalian lung in five different states: normal development, fibrosis, erosion, pneumonectomy, and the steady state. Deposition is the net result of positive and negative processes. The major positive processes are control of cell number and type, regulation of transcription and translation, post-translational modifications, fibril formation, and covalent cross-linking. The negative mechanisms are intracellular degradation, collagenase-mediated degradation, and phagocytosis, and they are integral to the life cycle of collagen. Cytokines and growth factors have many and complex effects on all the processes that constitute collagen metabolism. Interleukin-1 and tumor necrosis factor-alpha can either stimulate or inhibit collagen accumulation, presumably depending on the immediate environment. Interleukin-6 inhibits collagen degradation, and gamma-interferon inhibits collagen production. Platelet derived growth factor and fibroblast growth factor have powerful mitogenic effects on connective tissue cells in lung, and can also affect collagen production directly. Transforming growth factor-beta activates a battery of processes that uniformly contribute to accumulation of collagen. Transforming growth factor-beta may be the "master switch" for a fibrotic program in lung. Therapeutic approaches to controlling lung fibrosis by manipulating cytokine levels are promising. Prostaglandin E has uniformly negative effects on net collagen accumulation and may play a central role in an erosion program. PMID- 7770463 TI - Protection of mice from teratogen-induced cleft palate by exogenous methionine. AB - A major challenge for biomedical research is the reduction and/or prevention of congenital craniofacial abnormalities which can be induced by some extrinsic toxicants such as retinoic acids (e.g. isotretinoin, Accutane) and glucocorticoids (corticosteroid hormones) during embryonic craniofacial morphogenesis. Our present studies using a genetically susceptible mouse strain (B10.A) indicate that the teratogenic actions of exogenous retinoic acid or glucocorticoid in secondary cleft palate induction can be largely reduced or even completely rescued by subsequent administration of methionine. The greatest reduction in frequency of all-trans retinoic acid- or triamcinolone-induced secondary cleft palate was obtained by a single-dose IP administration of methionine at 187 mg/kg to pregnant mice on E13 21 hr. It appears that detrimental toxic effects were not observed in mice treated with this therapeutic level of methionine. Our present findings support the need for further research into the role of exogenous methionine in cleft palate reduction, that will provide a biological rationale for considering methionine as a therapeutic agent. PMID- 7770464 TI - Glucocorticoid metabolism in the newborn rat heart. AB - A relative cardiac hypertrophy has been observed in newborns chronically treated with dexamethasone. To test the hypothesis--that dexamethasone might alter steroid metabolism within the heart--rat pups were injected with vehicle, corticosterone (dosages 20 or 200 micrograms/pup/injection, or 1 mg/pup/injection) or dexamethasone (5 micrograms/pup/injection) on Day 2-6 and sacrificed on Day 7-8. Injections with dexamethasone in this dosage have induced the cardiac changes in this rat model. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) activity was assessed in hearts from these adrenally intact rat pups by incubating tissues with 3H-corticosterone 10(-8) M for 60 min. On Day 7-8, controls transformed 10.3% +/- 1.1% (mean +/- SE) of the corticosterone (Compound B) to 11-dehydrocorticosterone (Compound A) generating 1.25 +/- 0.35 x 10(-12) moles A/mg protein (n = 8). Tissues from pups pretreated with corticosterone at all three dosages were not different from controls in percent metabolized and moles A/mg generated. In contrast, hearts from dexamethasone treated pups transformed only 4.5% +/- 1.0% of the corticosterone to A generating 3.19 +/- 0.05 x 10(-13) moles A/mg protein (n = 10) (P < 0.05 versus control in moles/mg protein metabolized). Cultured cardiomyocytes exposed to dexamethasone for 4 days in vitro also decreased their expression of 11 beta-OHSD mRNA. Readily metabolized endogenous glucocorticoids produced little or no effect on developing heart muscle while treatment with dexamethasone, a potent synthetic glucocorticoid, induced relative cardiac hypertrophy and downregulated 11 beta OHSD mRNA expression and enzyme activity. PMID- 7770465 TI - Growth attenuation in a human prostate cell line mediated by a phorbol ester. AB - Human prostatic cancer cells JCA-1 were induced with a phorbol ester 12-o tetradecanoylphorbol-13-acetate (TPA), and cell growth differentiation were analyzed. Within hours of exposure to TPA, cell proliferation decreased and reached approximately 80% reduction after 3 days, as determined by [3H]thymidine incorporation and cell counting. Cell cycle analysis revealed a blocking of cells entering into the replicating S and G2M phases from the G1 phase. The TPA induced cells had a reduced growth rate but remained viable. The growth-modulating activity of TPA was similarly observed with LNCaP cells. Agarose gel electrophoresis of the chromosomal DNA from induced cells exhibited a non fragmented pattern excluding the possibility of cell apoptosis. In parallel to the growth reduction, the TPA induced cells became larger in size showing dendrite like cytoplasmic extensions. Furthermore, JCA-1 cells treated with TPA acquired the expression of cytokeratin 18 and increased the expression of actin and vimentin by 300%. These results indicate an induced growth reduction accompanied by cellular differentiation of the prostatic cancer cells. PMID- 7770466 TI - Beta-adrenoceptor changes in mononuclear leukocytes during pregnancy. AB - Leukocyte beta 2-adrenoceptors mirror similar receptors in the uterus. This study examined changes in beta 2-adrenoceptors and in cAMP production during pregnancy using peripheral mononuclear leukocytes isolated from 17 pregnant women and 5 nonpregnant controls. beta 2-Adrenoceptor density was determined by 125I-pindolol binding. cAMP production under basal and stimulated (10 microM isoproterenol) conditions was determined by radioimmunoassay. Groups were compared by unpaired t test. There was a nonsignificant decrease in the density of beta-adrenoceptors during pregnancy. While basal cAMP production was unchanged during pregnancy, stimulated cAMP production was decreased (44% of control, P < 0.001; 95% CI 33% 56%). Stimulated cAMP production per receptor was lower in leukocytes from pregnant women and was not a constant relationship, but was increased markedly in leukocytes having fewer than 400 beta-adrenoceptor sites per cell. There are significant changes in the coupling of beta-adrenoceptors to cAMP production during pregnancy without changes in beta-receptor density, affinity, or basal cAMP production. PMID- 7770467 TI - Possible changes in the regulatory mechanisms of pulsatile luteinizing hormone secretion in adult pituitary-grafted female rats. AB - It is well known that LH is released in an episodic fashion. However, the effects of hyperprolactinemia on luteinizing hormone (LH) pulsatility are not fully understood. The present study was undertaken to describe hyperprolactinemia effects on the regulatory mechanism of LH pulsatility. For this purpose hyperprolactinemia was induced in female rats by the transplantation of two pituitary glands beneath the kidney capsule. Age-matched sham-operated animals were used as controls. We have evaluated the pulsatile pattern of LH in both groups of animals. As expected, pituitary grafting increased mean serum prolactin levels compared with the values found in control animals. Luteinizing hormone releasing hormone (LHRH) administration did not change serum prolactin levels in control or in pituitary-grafted rats. Thyrotropin-releasing hormone (TRH) administration increased prolactin secretion in both groups. There is an increase in mean values of LH and in the absolute amplitude of LH peaks in pituitary grafted compared with control rats. No other parameters of LH pulsatility were changed by pituitary grafting. After LHRH administration, LH release was increased and a priming effect after the second administration of LHRH is observed in control rats. In pituitary-grafted animals the responses of LH to LHRH administration was diminished compared with the response observed in control rats. The administration of two pulses of TRH to control rats only decreases the duration of LH pulses. However, in pituitary-grafted animals, TRH administration was followed by a decrease in the mean values of LH and in the absolute amplitude of the LH peaks. Vasoactive intestinal peptide (VIP) administration increased mean values of LH and the absolute and relative amplitudes of LH pulses in sham operated animals, whereas only the relative amplitude of LH peaks was modified by VIP in pituitary-grafted rats. All these data suggest that hyperprolactinemia induced by pituitary-grafting interfere with the neuromodulator effects on the pulsatile regulatory center of the hypothalamus. PMID- 7770468 TI - Developmental changes in newborn lamb brain mitochondrial activity and postasphyxial lipid peroxidation. AB - Previously, our laboratory has demonstrated inhibition of mitochondrial state 3 (ADP-dependent) respiration 5 min after resuscitation from an asphyxial insult in lambs less than 3 days of age. Older lambs were resistant to this transient mitochondrial dysfunction. This study was designed to examine if age-related differences in baseline state 3 mitochondrial respiration, electron transport chain activity, or susceptibility to oxygen free radical-mediated lipid peroxidation were related to the previously observed differences in postasphyxial mitochondrial respiration. Mitochondrial respiration was measured in 24 nonasphyxiated control lambs aged 1-10 days using four different substrates. Electron transport chain activity was assessed in 15 of these lambs, and lipid peroxidation measured as conjugated diene production was measured in 11 of these lambs. These lambs were all ventilated to maintain normal blood gases for a time period equal to the length of the hypoxic insult in asphyxiated lambs (see below), after which samples of brain were removed for isolation of mitochondria. A second group of 11 lambs (seven < or = 3 days of age and four > 3 days of age) were asphyxiated. The insult was a 75-to-90-min episode of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 min of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 min after resuscitation. Postasphyxia electron transport chain activity and lipid peroxidation were measured. All measurements described above were done in both nonsynaptic (primarily glial in origin) and synaptic mitochondria. State 3 mitochondrial respiration varied significantly with age, decreasing by an average of 41.2% +/- 11.1% (mean +/- SEM) from Day 2 to Day 5-6 and then increasing back to levels similar to Day 2 by Day 8-10 in nonsynaptic mitochondria. State 3 respiration in synaptic mitochondria decreased 60.6% +/- 5.2% from Day 2 to Day 5 6 before returning to levels similar to Day 2 by Day 8-10. Resting (nonADP dependent) state 4 respiration demonstrated similar developmental patterns. Electron transport chain activities did not vary with age in the nonasphyxiated control animals. In addition, an asphyxial insult did not diminish electron transport chain activities in either lambs < or = 3 days old or those > 3 days of age.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7770469 TI - Deleterious effects of buthionine sulfoximine on cardiac function during continuous endotoxemia. AB - Sepsis has been associated with reversible cardiac injury. To determine whether this injury is mediated by generation of reactive oxidants, tissue glutathione (GSH)--the major intracellular antioxidant--was depleted before endotoxemia. Basal values of cardiac contractile function, perfusion, and cardiac output were measured 5-7 days postsurgery. Salmonella enteritidis endotoxin was continuously infused at 3 micrograms/kg/hr iv via an osmotic pump (Alzet Corp). Endotoxemia significantly reduced myocardial glutathione content (394 +/- 46) to 206 +/- 9 micrograms/g), indicating oxidant stress during endotoxemia. Buthionine sulfoximine (BSO) pretreatment significantly reduced cardiac glutathione in sham pigs from 394 +/- 46 to 199 +/- 26 micrograms/g; and in endotoxemic pigs, BSO pretreatment significantly reduced cardiac glutathione to 106 +/- 18 micrograms/g. Vehicle- and BSO-treated endotoxemic groups demonstrated similar cardiovascular responses to endotoxin challenge. Heart rate increases (122 +/- 15 to 140 +/- 17 bpm) and cardiac outputs decreases (1.50 +/- 0.24 to 1.11 +/- 0.35 l/min) were similar, indicating similar cardiovascular insults induced by endotoxemia. Percent short axis shortening and end-systolic pressure-diameter relation (ESPDR) were significantly reduced in BSO pretreated compared with vehicle-treated endotoxemic pigs. Results support a conclusion that endotoxemia induced cardiac injury is mediated, in part, by free radical injury. This conclusion is based upon the finding that endogenous myocardial glutathione was depleted by continuous endotoxin infusion and that prior depletion of myocardial glutathione by buthionine sulfoximine exacerbated cardiac injury. PMID- 7770470 TI - Single nephron hemodynamics in spontaneously hypertensive rats. AB - This study was designed to determine whether glomerular hypertension develops as a function of age in the spontaneously hypertensive rat (SHR). Male SHR and age matched Wistar-Kyoto (WKY) normotensive controls were divided into three groups for measurements of whole kidney and single nephron hemodynamics at 5, 10, and 15 months of age. As reported previously, SHR developed significant proteinuria which was predominantly an albuminuria, after 5 months of age. There were no differences in whole kidney or single nephron glomerular filtration rates between SHR and WKY. Afferent glomerular capillary hydraulic pressure (PGC) was slightly increased in SHR compared with WKY at 10 months of age. At 15 months of age, PGC in SHR was significantly lower than WKY. Our studies indicate that increased capillary pressure is not a major factor in the development and progression of renal injury in the spontaneously hypertensive rat. PMID- 7770471 TI - A method to quantitatively compare in vivo the effects of gallstone solvents on intestinal mucosal function: a controlled study comparing mono-octanoin with methyl tert-butyl ether in the rat. AB - During contact dissolution of gallstones, solvents may escape from the gallbladder and damage the intestinal mucosa. In order to compare the extent of this potential injury, we developed a method to objectively quantify the effects of two commonly used cholesterol solvents, methyl tert-butyl ether and mono octanoin, on mucosal transport function in the rat intestine. Two intestinal segments in each of 184 anesthetized rats were cannulated. Three milliliters of either solvent were instilled in one segment and left for varying periods of time, while saline was instilled in the other as control. The segments were then washed and perfused for 45 min with an isotonic solution containing [3H]polyethylene glycol 4000 (a nonabsorbable reference marker) and either [14C]alpha-aminoisobutyric acid (a marker for active absorption) or [14C]mannitol (a marker for passive permeability). Methyl tert-butyl ether caused more inhibition of alpha-aminoisobutyric acid absorption (64%) than mono-octanoin (48%) and a greater reduction of dry weight per centimeter of the perfused segment (22%) compared with mono-octanoin (10%). Such effects appeared after only 1 min of solvent exposure and did not appreciably increase with longer exposures. Permeation of mannitol increased by 26% after 1 min of exposure to mono-octanoin and by 54% after a similar period of exposure to methyl tert-butyl ether. Longer exposures to both solvents did not seem to cause progressive increases in mannitol permeation. The results indicate that brief exposure of the rat jejunum to either of the two solvents causes a reduction in active transport ([14C]alpha aminoisobutyric acid absorption), an increase in passive permeability (mannitol permeation), and a loss of mucosal constituents. We conclude that the intestinal mucosa is susceptible to solvent damage and may be used as a selectively sensitive model that can characterize the biological injury of gallstone solvents. The study also suggests that escape of the currently available solvents into the small intestine in patients undergoing contact dissolution of gallbladder stones may cause injury to the small intestine. PMID- 7770472 TI - Cellular sterol accumulation stimulated by cholesterol 5 beta,6 beta-epoxide in J774 macrophages. AB - A significant accumulation of cellular free cholesterol and steryl esters is observed in J774 macrophages when cells are exposed to low-density lipoproteins (LDL) containing cholesterol 5 beta,6 beta-epoxide. This cellular sterol accumulation is mainly due to the formation of esterified cholesterol and desmosterol. Cellular steryl esters increased to 39.4 and 22.4 micrograms/mg cell protein with 0.8 microM of cholesterol 5 beta,6 beta-epoxide and 3,5-cholestadien 7-one, respectively, whereas hardly detectable levels were observed with the absence of oxysterols. The total cellular sterols increased 45% above the value of control with cholesterol 5 beta,6 beta-epoxide. The uptake of [3H] cholesteryl oleate-LDL was also enhanced by cholesterol 5 beta,6 beta-epoxide. The rapid displacement of desmosterol with cholesterol was observed when cells were treated with cholesterol 5 beta,6 beta-epoxide or 3,5-cholestadien-7-one in the presence of LDL. Cholesterol 5 beta,6 beta-epoxide became associated with LDL in the culture conditions, and its uptake into J774 cells and the cytotoxicity were reduced significantly by the association with LDL. The comparison of selected oxysterols for their ability to stimulate cellular sterol accumulation indicated that cholesterol 5 beta,6 beta-epoxide is the most potent. Cholesterol esterification was enhanced significantly by cholesterol 5 beta,6 beta-epoxide whereas cholesterol 5 alpha,6 alpha-epoxide and 3,5-cholestadien-7-one produced a modest response. In contrast, although cholestantriol, the metabolic hydrolysis product of cholesterol epoxides, also associated with LDL, it showed no stimulating effect on both cellular sterol content and sterol esterification. These results indicate that some oxysterols, such as cholesterol 5 beta,6 beta epoxide and possibly 3,5-cholestadien-7-one, stimulate cellular sterol accumulation in J774 macrophages and may play an important role in atherogenesis. PMID- 7770473 TI - Ilya Mechnikov and his studies on comparative inflammation. AB - Mechnikov was born in Russia in 1845 and died in Paris in 1916. During his studies of embryogenesis and digestive function, he developed the concept of phagocytosis as a biologic phenomenon. He joined the Pasteur Institute in 1888 at Pasteur's invitation as Chef de Service there, studying inflammation and immunity in many species--both unicellular and high orders. In 1908, he was awarded the Nobel Prize in Medicine and Physiology with Paul Ehrlich. PMID- 7770474 TI - gamma-Propoxy-sulfo-lichenin, an antitumor polysaccharide derived from lichenin. AB - A water-soluble semisynthetic polysaccharide, gamma-propoxy-sulfo-lichenin (PSL), was prepared by reaction of propansultone with lichenin, a natural occurring beta 1.3/1.4-linked glucan originating from Cetraria sp. PSL represents a class of mixed-linked beta-glucans with long and hydrophilic side chains in position C-6 of the glucan backbone. PSL with a degree of substitution of 0.8 and an average molecular weight of 250 kDa exhibited a strong antitumor activity in doses of 25 and 5 mg/kg against solid sarcoma 180 (100% resp. 82% tumor inhibition). The antitumor activity of PSL was shown to be dependent on the dimension of the molecule: the higher the average molecular weight, the higher was the inhibition rate obtained in the antitumor assay. No antitumor effect was observed by using a pretreatment of animals prior to transplantation of sarcoma 180. On syngenic DBA/2-MC.SC1 fibrosarcoma PSL inhibited tumor growth by about 88% at a concentration of 25 mg/kg. PSL failed to exhibit any direct cytotoxic effects on hormone-independent MDA-MB 231 mammacarcinoma. For PSL an indirect antitumor effect via modulation of the host mediate immune defence is postulated. PMID- 7770475 TI - Dermal metabolism of topically applied drugs: pathways and models reconsidered. AB - The study of skin metabolism is of prime importance not only in the field of transdermal drug delivery but also for the safe and efficient local skin treatment with topically applied substances. Since it has become clear that even peptides may be delivered across the permeation barrier of the stratum corneum, e.g. by means of iontophoresis, phonophoresis or electroporation, the enzymatic barrier of the epidermis deserves more attention as another important limiting factor for the dermal delivery of drugs. The purpose of this review is to give a survey of the major aspects concerning the assessment of the metabolism of xenobiotics in the skin. First, this review will focus on the localization of enzyme activity within the skin. Further, important aspects to be considered for the planning and evaluation of skin metabolism studies will be discussed: differences among species and requirements of skin quality. Among the various metabolic pathways within the skin broad interest will be concentrated on the metabolism of peptide drugs. Therefore, exopeptidases in the skin are the subject of an additional section. Also models for skin metabolism studies will be especially considered including the development of suitable cell culture models. Finally, major gap areas in the investigation of skin metabolism will be identified and summarized, namely; classes of xenobiotics, proteolytic enzyme activity in the skin, validity of experimental models, localization of enzyme activity and physical model development. PMID- 7770476 TI - Secondary structure prediction of adenylate kinase by circular dichroism spectroscopy of synthetic peptides. AB - The synthesis of 13 segments of porcine adenylate kinase (AK 1) consisting each of 15 residues and covering the whole sequence of AK 1 is reported. The peptides were obtained by multiple peptide synthesis applying Fmoc/tert. butyl strategy. For the conformational analysis by circular dichroism spectroscopy different mixtures of phosphate buffer (pH 7), trifluoroethanol and methanol were used. Ten peptides showed alpha-helical conformation in all solvents except of pure buffer. The conformation of these peptides correlated well with the secondary structure obtained by homology modelling and even more striking with the X-ray structure of adenylate kinase, which was published recently. In contrast, three peptides, which were suggested to adopt no helical conformation did not show any content of alpha-helicity in any of the solvents that we investigated. One peptide, which contains a beta-sheet according to the X-ray analysis revealed a high content of beta-conformation by CD in buffer and in mixtures with trifluoroethanol. The two other peptides revealed mainly random coil in all solvents which we investigated. Therefore, we conclude that synthetic peptides are suitable tools to investigate the secondary structure of protein segments and that this conformation is frequently preserved in the intact protein. PMID- 7770477 TI - The comparative histology of porcine and guinea pig skin with respect to iontophoretic drug delivery. AB - The anatomy of pig skin, neonatal pig skin, and hairless guinea pig skin was investigated with respect to iontophoretic drug transport. Fixed sections of skin were stained with hematoxylin and eosin, and the morphology of the skin appendages was examined. Quantitative measurements of the hair follicle density, diameter and lumen area were obtained, and the effective surface areas available for low resistance iontophoretic transport were calculated. The clustering and density of the follicles of neonatal porcine skin and hairless guinea pig skin suggest that linear mass transport may dominate iontophoretic flux. In contrast, the morphology and density of the hair follicles of porcine skin suggests that a radial mass transport mechanism may dominate iontophoretic transdermal drug delivery. PMID- 7770478 TI - The prediction of the lipophilicity of peptidomimetics. A comparison between experimental and theoretical lipophilicity values of renin inhibitors and their building blocks. AB - In order to test how well the lipophilicity of large and flexible molecules can be predicted by theoretical approaches, renin inhibitors and their building blocks have been investigated. Different experimental methods have been used for the determination of lipophilicity of the selected compounds, including RP-HPLC and a new pH-metric or two-phase titration method. This latter method appears to be well-suited for the log P measurement of lipophilic compounds. The experimental results have been compared to computer-assisted log P calculations (CLOGP and PrologP). Different correction terms have been introduced to correlate the experimental to the calculated results. Finally, in view of the poor oral bioavailability of most renin inhibitors, we have investigated the correlation between aqueous solubility data and their log P values. PMID- 7770479 TI - Principles of chaperone-mediated protein folding. AB - The recent discovery of molecular chaperones and their functions has changed dramatically our view of the processes underlying the folding of proteins in vivo. Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformations in a reaction mediated by chaperone proteins. Different classes of molecular chaperones, such as the members of the Hsp70 and Hsp60 families of heat-shock proteins, cooperate in a coordinated pathway of cellular protein folding. PMID- 7770480 TI - Mapping the structures of transition states and intermediates in folding: delineation of pathways at high resolution. AB - The structures of all the intermediates and transition states, from the unfolded state to the native structure, are being determined at the level of individual residues in the folding pathways of barnase and chymotrypsin inhibitor 2 (CI2), using a combination of protein engineering and nuclear magnetic resonance methods. Barnase appears to refold according to a classical framework model in which elements of secondary structure are flickeringly present in the denatured state, consolidate as the reaction proceeds and, when nearly fully formed, dock in the rate-determining step. Unlike barnase, CI2 folds without a kinetically significant folding intermediate. The transition state for its formation has no fully formed elements of secondary structure, and the transition state is like an expanded form of the native structure. CI2 probably represents the folding of an individual domain in a larger protein, whereas barnase represents the folding of a multi-domain protein. The protein engineering methods are being extended to map the pathway in the presence of molecular chaperones. There are parallels between the folding of barnase when bound to GroEL and in solution. PMID- 7770481 TI - Unliganded GroEL at 2.8 A: structure and functional implications. AB - The three-dimensional structure of the E. coli chaperonin, GroEL, has been determined crystallographically and refined to 2.7 A in two crystal forms: an orthorhombic form from high salt and a monoclinic form from polyethylene glycol. The former is ligand free, the latter is both liganded with ATP analogues and ligand free. These structures provide a structural scaffold upon which to interpret extensive mutagenesis and biochemical studies. GroEL contains two sevenfold rotationally symmetric rings of identical 547-amino acid subunits. The rings are arranged 'back-to-back' with exact dyad symmetry to form a stubby cylinder that is 146 A high with an outer diameter of about 143 A. The cylinder has a substantial central channel that is unobstructed for the entire length of the cylinder and has a diameter of about 45 A except for large bulges that lead into a sevenfold symmetric array of elliptical side windows in each ring. Each subunit is composed of three distinct domains: (i) an 'equatorial' domain that contains the N- and C-terminus and the ATP-binding pocket, (ii) an 'apical domain' that forms the opening of the central channel and contains poorly ordered segments that mutational studies implicate in binding unfolded polypeptides and GroES, and (iii) an intermediate domain tht connects the other two domains and may serve to transmit allosteric adjustments. PMID- 7770482 TI - Insights into protein folding using physical techniques: studies of lysozyme and alpha-lactalbumin. AB - Understanding the process of protein folding, during which a disordered polypeptide chain is converted into a compact well-defined structure, is one of the major challenges of modern structural biology. In this article we discuss how a combination of physical techniques can provide a structural description of the events which occur during the folding of a protein. First, we discuss how the rapid kinetic events which take place during in vitro folding can be monitored and deciphered in structural terms. Then we consider how more detailed structural descriptions of intermediates may be obtained from NMR studies of stable, partly folded states. Finally, we discuss how these experimental strategies may be extended to relate the findings of in vitro studies to the events occurring during folding in vivo. The approaches will be illustrated using results primarily from our own studies of the c-type lysozymes and the homologous alpha lactalbumins. The conclusions from these studies are also related to those from other systems to highlight their unifying features. On the basis of these results we identify some of the determinants of the events in folding and we speculate on the importance of these in driving folding molecules to their native states. PMID- 7770483 TI - Initial studies of the equilibrium folding pathway of staphylococcal nuclease. AB - Spectroscopic methods were used to examine the sequential build up of structure in the denatured state of staphylococcal nuclease. The 'free energy distance' between the native and denatured states was manipulated by altering conditions in solution (for example altering urea or glycerol concentration) and by changing the amino acid sequences. Initial studies employed a fragment of nuclease, referred to as delta 131 delta, which lacks six structural residues from the amino terminus and one structural residue from the carboxy-terminus. Nuclear magnetic resonance analysis of this fragment in solution revealed a modest quantity of dynamic structure which is native-like in character. With the addition of urea, 12 new HN peaks appeared in the 1H-15N correlation spectrum, presumably as a result of the breakdown of residual structure involving the first three beta strands. With the addition of glycerol, there was a rapid increase in the quantity of beta sheet structure detected by circular dichroism spectroscopy. At very high glycerol concentrations, an increase in helical structure became apparent. These data in addition to previously published results suggest that: (i) a beta-meander (strands beta 1-beta 2-beta 3) and the second alpha helix (alpha 2) are among the most stable local structures; (ii) the five-strand beta barrel forms in a reaction which does not require the presence of several other native substructures; and (iii) the last step on the equilibrium folding pathway may be the formation and packing of the carboxy terminal alpha helix (alpha 3) to give the native state. PMID- 7770484 TI - Kinetic and equilibrium folding intermediates. AB - Our recent experiments on the molten globule state and other protein folding intermediates lead to following conclusions: (i) the molten globule is separated by intramolecular first-order phase transitions from the native and unfolded states and therefore is a specific thermodynamic state of protein molecules; (ii) the novel equilibrium folding intermediate (the 'pre-molten globule' state) exists which can be similar to the 'burst' kinetic intermediate of protein folding; (iii) proteins denature and release their non-polar ligands at moderately low pH and moderately low dielectric constant, i.e. under conditions which may be related to those near membranes. PMID- 7770485 TI - Does the molten globule have a native-like tertiary fold? AB - One of the mysteries in protein folding is how folding intermediates direct a protein to its unique final structure. To address this question, we have studied the molten globule formed by the alpha-helical domain of alpha-lactalbumin (alpha LA) and demonstrated that it has a native-like tertiary fold, even in the absence of rigid, extensive side chain packing. These studies suggest that the role of molten globule intermediates in protein folding is to maintain an approximate native backbone topology while still allowing minor structural rearrangements to occur. PMID- 7770486 TI - Investigation of protein unfolding and stability by computer simulation. AB - Structural, dynamic and energetic properties of proteins in solution can be studied in atomic detail by molecular dynamics computer simulation. Protein unfolding can be caused by a variety of driving forces induced in different ways: increased temperature or pressure, change of solvent composition, or protein amino acid mutation. The stability and unfolding of four different proteins (bovine pancreatic trypsin inhibitor, hen egg white lysozyme, the surfactant protein C and the DNA-binding domain of the 434 repressor) have been studied by applying the afore-mentioned driving forces and also to some artificial forces. The results give a picture of protein (in)stability and possible unfolding pathways, and are compared to experimental data where possible. PMID- 7770487 TI - Disulphide-coupled protein folding pathways. AB - Protein folding pathways that involve disulphide bond formation can be determined in great detail. Those of bovine pancreatic trypsin inhibitor, alpha-lactalbumin and ribonucleases A and T1 are compared and contrasted. In each species, whatever conformation favours one disulphide bond over another is stabilized to the same extent by the presence of that disulphide bond in the disulphide intermediates. The pathways differ markedly in the nature of that conformation: in bovine pancreatic trypsin inhibitor a crucial intermediate is partly folded, in alpha lactalbumin the intermediates tend to adopt to varying extents the molten globule conformation, while in the ribonucleases the early disulphide intermediates are largely unfolded, and none predominate. In each case, however, the slowest step is formation of a disulphide bond that will be buried in a stable folded conformation; the most rapid step is formation of an accessible disulphide bond on the surface of a folded conformation. Quasi-native species with the native conformation, but incomplete disulphide bonds, can either increase or decrease the rate of further disulphide formation. PMID- 7770488 TI - Models of cooperativity in protein folding. AB - What is the basis for the two-state cooperativity of protein folding? Since the 1950s, three main models have been put forward. 1. In 'helix-coil' theory, cooperativity is due to local interactions among near neighbours in the sequence. Helix-coil cooperativity is probably not the principal basis for the folding of globular proteins because it is not two-state, the forces are weak, it does not account for sheet proteins, and there is no evidence that helix formation precedes the formation of a hydrophobic core in the following pathways. 2. In the 'sidechain packing' model, cooperativity is attributed to the jigsaw-puzzle-like complementary fits of sidechains. This too is probably not the basis of folding cooperativity because exact models and experiments on homopolymers with sidechains give no evidence that sidechain freezing is two-state, sidechain complementarities in proteins are only weak trends, and the molten globule model predicted by this model is far more native-like than experiments indicate. 3. In the 'hydrophobic core collapse' model, cooperativity is due to the assembly of non-polar residues into a good core. Exact model studies show that this model gives two-state behaviour for some sequences of hydrophobic and polar monomers. It is based on strong forces. There is considerable experimental evidence for the kinetics this model predicts: the development of hydrophobic clusters and cores is concurrent with secondary structure formation. It predicts compact denatured states with sizes and degrees of disorder that are in reasonable agreement with experiments. PMID- 7770489 TI - Protein folds: towards understanding folding from inspection of native structures. AB - Following a short summary of some of the principal features of folded proteins, the results of two complementary studies of protein structure are presented, the first concerned with the factors which influence secondary structure propensity and the second an analysis of protein topology. In an attempt to deconvolute the physical contributions to secondary structure propensities, we have calculated intrinsic phi, psi propensities, derived from the coil regions of proteins. Comparison of intrinsic phi, psi propensities with their equivalent secondary structure values show correlations for both helix and strand. This suggests that the local dipeptide, steric and electrostatic interactions have a major influence on secondary structure propensity. We then proceed to inspect the distribution of protein domain folds observed to date. Several folds occur very commonly, so that 46% of the current non-homologous database comprises only nine folds. The implications of these results for protein folding are discussed. PMID- 7770490 TI - Design of two-stranded and three-stranded coiled-coil peptides. AB - The structural features required for the formation of two- versus three-stranded coiled coils have been explored using de novo protein design. Peptides with leucine at the 'a' and 'd' positions of a coiled-coil (general sequence: Leua Xaab Xaac Leud Glue Xaaf Lysg) exist in a non-cooperative equilibrium between unstructured monomers and helical dimers and helical trimers. Substituting valine into each 'a' position produces peptides which still form trimers at high concentrations, whereas substitution of a single asparagine at the 'a' position of the third heptad yields a dimer. During the course of this work, we also re investigated a helical propensity scale derived using a series of coiled-coil peptides previously believed to exist in a monomer-dimer equilibrium (O'Neil & DeGrado 1990). Detailed analysis of the concentration dependence of ellipticity at 222 nm reveals that they exist in a non-cooperative monomer-dimer-trimer equilibrium. However, the concentration of trimer near the midpoint of the concentration-dependent transition is small, so the previously determined values of delta delta G alpha using the approximate monomer-dimer scheme are indistinguishable from the values obtained employing the complete monomer-dimer trimer equilibrium. PMID- 7770491 TI - Nascent chains: folding and chaperone interaction during elongation on ribosomes. AB - Monoclonal antibodies that detect folding intermediates in vitro were used to monitor the appearance of folded polypeptide chains during their synthesis on the ribosomes. Nascent immunoreactive chains of the bacteriophage P22 tail-spike protein and of the Escherichia coli beta 2 subunit of tryptophan-synthase were thus identified, suggesting that they can fold on the ribosomes. Moreover, the immunoreactivity of ribosome-bound tryptophan-synthase beta-chains of intermediate lengths was shown to appear with no detectable delay compared to their synthesis. This suggested that beta-chains start folding during their elongation on the ribosomes. However, newly synthesized incomplete beta-chains were shown to interact with chaperones while still bound to the ribosome. Because of the peculiar properties of the epitope recognized by the anti-tryptophan synthase monoclonal antibody used, it could not be concluded whether the immunoreactivity of the nascent beta-chains resulted from their ability to fold cotranslationally or from their association with chaperones which might maintain them in an unfolded, immunoreactive state. PMID- 7770492 TI - Folding and association versus misfolding and aggregation of proteins. AB - The acquisition of spatial structure in proteins may be described in terms of hierarchical condensation, with contributions of local interactions between next neighbours and the interactions between domains and subunits accumulating to create the marginal free energy of stabilization characteristic of the functional state of globular proteins. Domains represent independent folding units such that the overall kinetics divide into the sequential collapse of subdomains and domains and their merging to form the compact tertiary structure. In proceeding to oligomeric proteins, docking of subunits follows the formation of structured monomers. Thus, the overall mechanism of folding and association obeys consecutive uni-bimolecular kinetics. Beyond a limiting protein concentration, aggregation will outrun proper domain pairing and subunit association. In the cell, accessory proteins are involved in catalysis of the rate-determining steps of folding (proline isomerization and SH-SS exchange) and in the kinetic partitioning between folding and aggregation (chaperone action). The practical aspects of accessory proteins have been investigated in detail using immunotoxins and antibody fragments as examples. Additional concepts allowing off-pathway reactions in protein reconstruction to be kept to a minimum refer to pulse dilation, reverse micelles and immobilization of polypeptide chains on matrices. PMID- 7770493 TI - Screening for balance and mobility impairment in elderly individuals living in residential care facilities. AB - BACKGROUND AND PURPOSE: The rapid growth of the elderly population has resulted in a corresponding rise in the number of elderly individuals who experience disability during their lifetimes. The purpose of this study was to test the usefulness of four established clinical measures of balance, gait, and subjective perceptions of fear of falling as screening methods for referring community dwelling elderly individuals living in residential care facilities for detailed physical therapy evaluation and possible intervention. SUBJECTS: The subjects were a convenience sample of 53 elderly individuals living in two residential care facilities for the elderly. METHODS: Subjects were tested on each of four clinical measures of balance and mobility. Their performance on these measures was compared with a physical therapist's brief evaluation of disability and appropriateness for more detailed evaluation. The usefulness of these tools as screening methods was determined by calculating sensitivity and specificity levels using the physical therapist's evaluation as a standard. RESULTS: The sensitivity and specificity levels of the four clinical measures in their application as screening tests for referral to physical therapy were as follows: Berg Balance Scale, 84% and 78%; balance subscale of the Tinetti Performance Oriented Mobility Assessment, 68% and 78%; gait speed, 80% and 89%; and Tinetti Fall Efficacy Scale, 59% and 82%. The combination of two tests, Berg Balance Scale and gait speed, yielded the highest sensitivity of 91% and the highest specificity of 70% when a subject tested positive on at least one test. CONCLUSION AND DISCUSSION: These findings indicate the feasibility of developing screening methods for referring community-dwelling elderly individuals for a detailed physical therapy evaluation based on established clinical assessment measures, with a combination of tests measuring balance and gait demonstrating the most promising results. PMID- 7770494 TI - A treatment-based classification approach to low back syndrome: identifying and staging patients for conservative treatment. AB - We present a treatment-based classification approach to the conservative management of low back syndrome. The approach has three levels of classification based on historical information, behavior of symptoms, and clinical signs. We first distinguish patients whose conservative care can be managed predominantly and independently by physical therapists versus patients who require consultation with other services (eg, psychology) or who require referral because of possible serious nonmusculoskeletal pathology. Once patients who can be managed by physical therapists are identified, the next level of classification is to stage their condition with regard to severity. We propose three stages: stage I for patients in the acute phase where the therapeutic goal is symptom relief, stage II for patients in a subacute phase where symptom relief and quick return to normal function are encouraged, and stage III for selected patients who must return to activities requiring high physical demands and who demonstrate a lack of physical conditioning necessary to perform the desired activities safely. The remainder of the article focuses on a third level of classification for stage I only in which patients are classified into distinct categories that are treatment based and that specifically guide conservative management. The entire approach is diagnosis based, with specific algorithms and decision rules as well as examples presented. PMID- 7770495 TI - The rehabilitation of gait in patients with hemiplegia: a comparison between conventional therapy and multichannel functional electrical stimulation therapy. AB - BACKGROUND AND PURPOSE: Gait rehabilitation in patients with severe hemiplegia requires substantial effort. Preliminary studies indicate potential beneficial effects of using multichannel functional electrical stimulation (MFES) for gait rehabilitation in these patients. In this study, a new method of gait rehabilitation for nonambulatory patients with hemiplegia by means of MFES added to conventional therapy was introduced. The results of the method's application were evaluated by comparing it with conventional therapeutic methods. SUBJECTS: The proposed rehabilitation method was tested on a group of 20 patients with severe hemiplegia secondary to cerebrovascular accident. Subjects were randomly assigned to one of two groups. One group received 3 weeks of MFES followed by 3 weeks of conventional therapy. The other group received 3 weeks of conventional therapy followed by 3 weeks of MFES. METHODS: The effects of each therapeutic method were evaluated by measurements of temporal-distance variables and ground reaction forces and by assessment of each subject's physical status according to the Fugl-Meyer evaluation scale. RESULTS: There was improved performance of the subjects during MFES combined with conventional therapy as compared with conventional therapy alone. CONCLUSION AND DISCUSSION: The superiority of the MFES method as compared with conventional therapy was mainly attributed to the enhanced motor learning accomplished by application of MFES. These results, however, are preliminary, and further research is needed. PMID- 7770496 TI - Enhancing service productivity in acute care inpatient settings using a collaborative clinical education model. AB - BACKGROUND AND PURPOSE: Exposure of physical therapy students to acute inpatient settings is difficult to achieve because of staff shortages and 1:1 supervision. The purpose of this study was to examine the productivity effects of the 2:1 teaching model in the acute inpatient clinical setting. Changes in patient throughput and the amount of care provided were the measures used to define productivity. SUBJECTS: The work load measurement statistics of 8 Clinical Instructors (CIs) and 16 physical therapy students were examined. METHODS: The productivity of each CI during a control period was compared with the productivity of the CI-student team. RESULTS: Each CI-student team's mean productivity was greater during the clinical placement than during the control period when the CI worked independently. Even when the students' productivity measures were prorated by 0.6, the productivity was greater during the student placement than during the control period. CONCLUSION AND DISCUSSION: The study demonstrates that students make positive contributions to clinical service units that can exceed normal productivity levels of the CI. The 2:1 model has the potential to increase productivity while increasing the numbers of placements for academic programs in limited specialty areas. PMID- 7770497 TI - Rheumatoid arthritis: status of drug therapies. AB - This article describes the current drug therapies used to manage rheumatoid arthritis (RA). A brief description of the pathology, pathogenesis, and clinical features of RA is presented. The purpose of the article is to increase an awareness among physical therapists regarding the medications their patients might be taking and how these agents might influence the outcome of physical therapy intervention. The general approach to prescribing medication is presented according to the status of the disease. The attributes of nonsteroidal antiinflammatory drugs, corticosteroids, slow-acting antirheumatic drugs, and cytotoxic and experimental drugs used in RA are described. Given the potential benefits, side effects, and adverse reactions of these potentially powerful medications, it is important for the physical therapist to monitor closely what is happening to the patient with respect to the use or nonuse of the medication. PMID- 7770498 TI - Topical agents in burn and wound care. AB - With any open wound infection may occur. Many factors such as age and general health status may increase the likelihood of infection, but the size and depth of the wound are critical factors in determining the chronicity of any wound. Infection greatly adds to the morbidity associated with open wounds. An infected wound not only heals more slowly, there is also the risk of systemic infection and even death. Infected wounds also scar more severely and are associated with more prolonged rehabilitation. Topical therapeutic agents have been shown to be effective in the management of open skin wounds. These agents may assist less complicated healing and decrease the conversion of a partial-thickness injury to a full-thickness injury, and thereby reduce wound-related morbidity. Common topical agents with suggestions for application are discussed in this review. PMID- 7770499 TI - The use of ultrasound as an enhancer for transcutaneous drug delivery: phonophoresis. AB - Phonophoresis is the use of ultrasound (US) to enhance the delivery of topically applied drugs. The purposes of this article are (1) to review the basic principles of transcutaneous drug delivery, (2) to summarize the functional anatomy of the skin pertinent to phonophoresis, (3) to outline the physiological principles of US as an enhancer of topically applied drugs, (4) to review the literature on the efficacy of phonophoresis, (5) to discuss the relevance of US as an enhancer of topical drugs in the practice of physical therapy, and (6) to outline areas of needed research. Seventy-five percent of the studies reviewed reported positive effects of US on local subcutaneous drug diffusion, but some systemic effects were reported. This research review indicates that to maximize the clinical effectiveness of phonophoresis: (1) the topical drug (both the drug and the carrying agent) should transmit US; (2) the skin should be pretreated with US, heating, moistening, or shaving; (3) the patient needs to be positioned to maximize circulation during treatment; (4) a dressing that seals the area and prevents the escape of moisture should be applied after treatment; (5) an intensity of 1.5 W/cm2 should be used to capture both the thermal and nonthermal effects of the US; and (6) low-intensity US (0.5 W/cm2) should be used when treating open wounds or acute injuries. Research is needed to clarify what parameters of US will most efficiently facilitate topical drug diffusion, how often and for what duration US should be used to maximize local absorption of drugs, and which topical drugs can most effectively be used for phonophoresis. PMID- 7770500 TI - Iontophoresis: applications in transdermal medication delivery. AB - This article presents a review of the literature relating to iontophoresis. This technique has been used in physical therapy to introduce ionic medications through the skin, primarily for a local effect. Recently, there has been increased interest in using this technique for the transdermal delivery of medications, both ionic and nonionic. This article includes an overview of the history of iontophoresis and a discussion of the physico-chemical and biological factors affecting iontophoretic drug transfer for both local and systemic effects. Factors affecting skin injury and techniques for optimizing iontophoretic drug delivery through the use of current modulation, electrode construction, and skin permeation enhancers are also discussed. Clinical applications of iontophoresis in physical therapy and the pharmacology of selected medications are presented. Thoughts for future potential uses of this technique and needs for further research are also discussed. PMID- 7770502 TI - First, do no harm... PMID- 7770501 TI - Language that obscures. PMID- 7770503 TI - Life's lessons. PMID- 7770504 TI - Theoretical investigation of excimer and exciplex states of uracil and halogen derivatives: effect of nonparallelism of bases. AB - Theoretical modeling of initial steps of the photodimerization mechanism of uracil, 5-methyl-and 5-halogen derivatives was performed. The interaction energy of bases in stacked dimers in the ground and lowest excited states was calculated as a function of the distance between the base planes and of the rotation angles within the perturbation theory for the extended Huckel treatment. The existence of excimer and exciplex region on the potential surface of the excited state was revealed. The excimer (exciplex) geometry has the planes nonparallel with more close contact of the C5-C6 bonds as compared to the ground state of dimers. The results provide new information useful for understanding the photodimerization mechanism of bases and testifies that the singlet excimer state can be a precursor of the photodimerization reaction. PMID- 7770505 TI - Photophysical studies on human retinal lipofuscin. AB - Fluorescent material generated in the human retina accumulates within lipofuscin granules of the retinal pigment epithelium (RPE) during aging. Its presence has been suggested to contributed to various diseases including age-related macular degeneration. Because this material absorbs light at wave lengths as long as 550 nm, photophysical studies were performed to determine whether lipofuscin could contribute to light damage and to determine if its composition is similar to a synthetically prepared lipofuscin. Time-resolved experiments were performed to monitor (1) fluorescence decay, (2) the UV-visible absorption of longer-lived excited states and (3) the formation and decay of singlet oxygen at 1270 nm. Steady-state and time-resolved fluorescence studies indicate that human and synthetic lipofuscin have fluorophores in common. Time-resolved absorption experiments on human retinal lipofuscin and synthetic lipofuscin showed the presence of at least two transient species, one absorbing at 430 nm (lifetime ca 7 microseconds) and a second absorbing at 580 nm, which decays via second order kinetics. In addition, there is a third absorbing species stable to several hundred milliseconds. The transient species at 430 nm is quenched by oxygen, suggesting that it is a triplet state. Subsequent studies showed the formation of singlet oxygen, which was monitored by its phosphorescence decay at 1270 nm. These studies demonstrate that lipofuscin can act as a sensitizer for the generation of reactive oxygen species that may contribute to the age-related decline of RPE function and blue light damage. PMID- 7770506 TI - Ultraviolet-induced cell death is independent of DNA replication in rat kangaroo cells. AB - Rat kangaroo (Potorous tridactylus) cells have an efficient repair system for photoreactivation of lethal lesions induced by 254 nm UV. However, this ability is lost with increasing time after UV, being completely ineffective after 24 h. Critical events leading to UV-induced cell death must occur within this period of time. DNA synthesis was inhibited by the DNA polymerase inhibitor aphidicolin and the loss of the capability to photorepair lethal lesions was maintained as for replicating cells. Similar data were obtained in synchronized cells UV irradiated immediately before S phase. Under the same conditions, the ability to remove cyclobutane pyrimidine dimers by photoreactivation in these cells remained unchanged 24 h after irradiation. These data indicate that the critical events responsible for UV-induced cell death occur in the absence of DNA replication. PMID- 7770507 TI - Preferential inhibition of nucleosome assembly by ultraviolet-induced (6 4)photoproducts. AB - We reconstituted nucleosomes in vitro using two kinds of damaged pBR322 plasmid DNA carrying cyclobutane pyrimidine dimers (CPD) or (6-4)photoproducts. The results indicate that nucleosome assembly is inhibited preferentially by (6 4)photoproducts compared with CPD, suggesting that the regions carrying (6 4)photoproducts retain their nucleosome-free form, i.e. linker-like conformation until completion of the repair processes. PMID- 7770508 TI - Photoinactivation (365 nm) of vaccinia and herpes simplex viruses induced by a new built-in DNA photosensitizer: 4-thiothymidine. AB - The thymidine analogue 4-thiothymidine (s4T) strongly absorbs light at wavelengths in the UVA range (lambda max 335 nm) and we have examined the photoinactivation of vaccinia and herpes simplex viruses grown in the presence of this nucleoside. The cells used in this study (Vero, mouse 1D-TK+) were able to grow at the same rate when cultured in the presence of 2 mM s4T or 2 mM thymidine, albeit at a slower rate than control cells. Consistent with this finding, viruses grown in the presence of 1-4 mM s4T were obtained in reduced yield but retained full infectivity. Both viruses were specifically inactivated by irradiation with 365 nm light and their photosensitivity, as measured by the initial slope of the inactivation curve, increased in parallel with the concentration of s4T added to the culture medium. More than 90% of vaccinia virus grown in the presence of 4 mM s4T was inactivated. Organomercurial agarose chromatography of sheared DNA isolated from vaccinia virus grown in the presence of 2 mM s4T showed that approximately 2.5% of DNA fragments were specifically retained, as compared to 0.2% for control DNA. This value corresponds to at least one s4T residue incorporated per 30,000 nucleotides of vaccinia virus DNA. In fact, it is likely that this ratio is actually approximately 10 times higher because of the incomplete retention of control thiolated oligodeoxynucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770509 TI - On the induction of protective responses in Salmonella typhimurium strain TA1535/pSK1002 by UVA (365 nm). AB - Exposure to UVA (365 nm) led to growth delay, loss of viability and inhibition of 3H-thymidine incorporation into the cells of Salmonella typhimurium strain TA1535 containing multiple copies of a plasmid pSK1002 carrying a umuC'-'lacZ fusion gene. Ultraviolet-A induced umu gene expression, as monitored by the estimation of beta-galactosidase, in a linear fluence-dependent manner. The induction of umu gene expression increased with the increase of postirradiation incubation period of the cells in the LB-ampicillin (LBA) medium at 37 degrees C and leveled off from 2 h onward. The induction of gene expression depended on concomitant protein synthesis and represented the induction of the SOS response in the particular S. typhimurium cells used. The exposure to low fluences (sublethal) of UVA also led to the induction of an adaptive response in the same bacterial cells, which made them resistant to subsequent challenge by a much higher fluence of the same radiation. The adaptive response, as monitored by the assays of viability and beta-galactosidase units, increased with the period of exposure to sublethal fluences of UVA, attained a maximum at the UVA exposure of 4.5 kJ/m2 (15 min) and thereafter gradually decreased with further increase of UVA exposure period. Modulation studies involving D2O, LBA growth medium, different scavengers of free radicals and quenchers of activated oxygen species indicated the involvement of both hydroxyl free radicals and singlet oxygen in the UVA-induced umu gene expression. PMID- 7770510 TI - A multitherapy resistance factor from melanoma reveals that killing by near UV is different from genotoxic agents. AB - A diffusible multitherapy resistance factor (MTRF) is produced by Cloudman S91 melanoma cells in vitro. The MTRF decreases sensitivity of the target cell line, S91/amel, to gamma-irradiation, UVC (200-280 nm) and mitomycin C (MMC). In the present study, we demonstrate that MTRF also increases the survival of S91/amel after exposure to actinomycin D (AMD) and vinblastine (VBL). The MTRF is thus effective when target cells have been exposed to five genotoxic agents that act by different mechanisms. It does not alter the response to the same five agents of the S91/I3 producer cells, which are presumably saturated with the factor. The factor has no effect on the survival of S91/amel cells that have been exposed to lethal doses of near monochromatic UVB (280-320 nm) or UVA (320-400 nm) or to polychromatic FS20 lamps. The lack of effectiveness of MTRF after cells have been exposed to near (300-400 nm) UV radiation indicates that in this wavelength range, S91 melanoma cells are killed by mechanisms that are different from the lethal effects of the five genotoxic agents (gamma-irradiation, UVC, MMC, AMD and VBL) to which the target cells demonstrate a response. PMID- 7770511 TI - Induction of slowly developing alkali-labile sites in human P3 cell DNA by UVA and blue- and green-light photons: action spectrum. AB - Action spectra (365-520 nm) for the formation of DNA single-strand breaks (SSB) and slowly developing alkali-labile sites (SDALS) in human teratocarcinoma P3 cells in culture were determined. Induction of SDALS results from the absorption of blue- and green-light photons. The spectrum has a broad peak that is maximal between 400 nm to 500 nm and declines sharply above and below these wavelength regions. Negligible yields of SDALS were produced by photons at wavelengths of 365 nm or shorter and at 520 nm or longer, whereas for SSB, the action ioffeases with shorter wavelength throughout the whole spectral range studied. The configuration of the SDALS action spectrum suggests that the primary chromophore, and therefore possibly the photosensitizer, is a mixture of porphyrin and flavin residues. PMID- 7770512 TI - Local neurotoxicity of hematoporphyrin derivative following intracerebral injection. AB - The present study reports on toxicity of hematoporphyrin derivative (HpD) for normal brain tissue in vivo without the addition of light. Hematoporphyrin derivative was injected by slow infusion in rat brains. Histological examination was carried out for intervals after HpD administration, ranging from 0 h to 15 days. Ultrastructural changes were examined with transmission electron microscopy. The extent of the necrosis was determined for different HpD concentrations and compared with control animals infused with 0.9% saline. Leukocytic infiltration was observed at day 5. Transmission electron microscopy showed that nuclei of neurons were completely disintegrated 4 h after HpD administration. Furthermore disruption of myelin sheaths was observed. The extent of the necrosis decreased with lower HpD doses. Injection of 2 micrograms HpD in a volume of 4 microL (0.5 mg/mL) resulted in a virtually equal extension of the tissue damage, as compared to the mechanical damage in the control animals caused by the infusion procedure. PMID- 7770513 TI - On the source of the oscillations observed during in vivo zinc phthalocyanine fluorescence pharmacokinetic measurements in mice. AB - Surface-detected fluorescence spectroscopy can be used to monitor the pharmacokinetics of uptake and clearance of red-absorbing fluorophores such as zinc(II) phthalocyanine (ZnPc) in vivo. When this technique is applied to mice that have been fed on a normal chlorophyll-based diet, and particularly when measurements are performed in the abdominal region, oscillations are sometimes observed superimposed on the pharmacokinetic curve of the ZnPc. An oscillatory signal has also been observed arising from the abdominal region of control mice fed a normal diet but not injected with the ZnPc photosensitizer; this oscillatory component to the signal is reduced when mice are fed a chlorophyll free diet. The oscillatory signal component has been attributed to fluorescence arising from chlorophyll derivatives (pheophorbide/pheophytin) contained in the rodent food, whose concentration in the measured abdominal region changes substantially with time, presumably due to digestive processes. Thus it is important to be aware of the possibility of such artifactual contributions to in vivo fluorescence pharmacokinetic measurements. PMID- 7770514 TI - The role of transferrin receptor (CD71) in photodynamic therapy of activated and malignant lymphocytes using the heme precursor delta-aminolevulinic acid (ALA). AB - Endogenously generated protoporphyrin IX (PpIX) from exogenous ALA can be an effective photosensitizer. PpIX accumulation is inversely dependent on available intracellular iron, which is required for the conversion of PpIX to heme. Iron also is necessary for cell replication. Since iron can be toxic, intracellular iron levels are tightly controlled. Activated and proliferating cells respond to the demand for intracellular iron by upregulating membrane expression of the transferrin receptor (CD71) which is needed for iron uptake. We predicted that activated lymphocytes (CD71+) would preferentially accumulate PpIX because of their lower intracellular iron levels and because of competition for iron between ALA-induced heme production and cellular growth processes. Thus, the CD71+ cells could serve as PDT targets. Stimulation of human peripheral blood lymphocytes (PBL) with the mitogens, phytohemagglutinin A, concanavalin A and pokeweed prior to incubation with ALA results in PpIX accumulation correlating with level of activation. Activated lymphocytes expressing high levels of surface CD71 transferrin receptors generated more PpIX than those with low CD71 expression. Incubating activated cells in transferrin depleted medium (thereby decreasing the iron availability) further increased PpIX levels. Malignant, CD71+ T lymphocytes from a patient with cutaneous T-cell lymphoma (CTCL)/Sezary syndrome also accumulated increased PpIX levels in comparison to normal lymphocytes. PDT of activated lymphocytes and Sezary cells after ALA incubation demonstrated preferential killing compared to normal, unstimulated PBL. These findings suggest a possible mechanism for the selectivity of ALA PDT for activated CD71+ cells. They also indicate a clinical use for ALA-PDT in therapy directed towards the malignant lymphocytes in leukemias and lymphomas, and as animmunomodulatory agent. PMID- 7770515 TI - Transfer of T-DNA from Agrobacterium to the plant cell. AB - Agrobacterium tumefaciens is the causative agent of crown gall, a disease of dicotyledonous plants characterized by a tumorous phenotype. Earlier in this century, scientific interest in A. tumefaciens was based on the possibility that the study of plant tumors might reveal mechanisms that were also operating in animal neoplasia. In the recent past, the tumorous growth was shown to result from the expression of genes coded for by a DNA segment of bacterial origin that was transferred and became stably integrated into the plant genome. This initial molecular characterization of the infection process suggested that Agrobacterium might be used to deliver genetic material into plants. The potential to genetically engineer plants generated renewed interest in the study of A. tumefaciens. In this review, we concentrate on the most recent advances in the study of Agrobacterium-mediated gene transfer, its relationship to conjugation, DNA processing and transport, and nuclear targeting. In the following discussion, references for earlier work can be found in more comprehensive reviews (Hooykaas and Schilperoort, 1992; Zambryski, 1992; Hooykaas and Beijersbergen, 1994). PMID- 7770516 TI - Three classes of nuclear import signals bind to plant nuclei. AB - Three nuclear localization signals (NLS), including an unusual Mat alpha 2-like NLS from maize (Zea mays) R, were found to compete for binding to plant nuclei. In addition, the authentic yeast Mat alpha 2 NLS, which does not function in mammals, was shown to function in plants in vivo. Our results indicate that plants possess a site at the nuclear pore complex that recognizes the three known classes of NLSs. PMID- 7770517 TI - Cadmium-sensitive, cad1 mutants of Arabidopsis thaliana are phytochelatin deficient. AB - An allelic series of cad1, cadmium-sensitive mutants of Arabidopsis thaliana, was isolated. These mutants were sensitive to cadmium to different extents and were deficient in their ability to form cadmium-peptide complexes as detected by gel filtration chromatography. Each mutant was deficient in its ability to accumulate phytochelatins (PCs) as detected by high-performance liquid chromatography and the amount of PCs accumulated by each mutant correlated with its degree of sensitivity to cadmium. The mutants had wild-type levels of glutathione, the substrate for PC biosynthesis, and in vitro assays demonstrated that each of the mutants was deficient in PC synthase activity. These results demonstrate conclusively the importance of PCs for cadmium tolerance in plants. PMID- 7770518 TI - A cadmium-sensitive, glutathione-deficient mutant of Arabidopsis thaliana. AB - The roots of the cadmium-sensitive mutant of Arabidopsis thaliana, cad1-1, become brown in the presence of cadmium. A new cadmium-sensitive mutant affected at a second locus, cad2, has been identified using this phenotype. Genetic analysis has grown that the sensitive phenotype is recessive to the wild type and segregates as a single Mendelian locus. Assays of cadmium accumulation by intact plants indicated that the mutant is deficient in its ability to sequester cadmium. Undifferentiated callus tissue was also cadmium sensitive, suggesting that the mutant phenotype is expressed at the cellular level. The level of cadmium-binding complexes formed in vivo was decreased compared with the wild type and accumulation of phytochelatins was about 10% of that in the wild type. The level of glutathione, the substrate for phytochelatin biosynthesis, in tissues of the mutant was decreased to about 15 to 30% of that in the wild type. Thus, the deficiency in phytochelatin biosynthesis can be explained by a deficiency in glutathione. PMID- 7770519 TI - Cytokinin action is coupled to ethylene in its effects on the inhibition of root and hypocotyl elongation in Arabidopsis thaliana seedlings. AB - Cytokinins have profound effects on seedling development in Arabidopsis thaliana. Benzyladenine (BA) inhibits root elongation in light- or dark-grown seedlings, and in dark-grown seedlings BA inhibits hypocotyl elongation and exaggerates the curvature of apical hooks. The latter are characteristic ethylene responses and, therefore, the possible involvement of ethylene in BA responses was examined in seedlings. It was found that the inhibitory effects of BA on root and hypocotyl elongation were partially blocked by the action of ethylene inhibitors or ethylene-resistant mutations (ein1-1 and ein2-1). Ethylene production was stimulated by submicromolar concentrations of BA and could account, in part, for the inhibition of root and hypocotyl elongation. It was demonstrated further that BA did not affect the sensitivity of seedlings to ethylene. Thus, the effect of cytokinin on root and hypocotyl elongation in Arabidopsis appears to be mediated largely by the production of ethylene. The coupling between cytokinin and ethylene responses is further supported by the discovery that the cytokinin resistant mutant ckr1 is resistant to ethylene and is allelic to the ethylene resistant mutant ein2. PMID- 7770520 TI - Essential role of urease in germination of nitrogen-limited Arabidopsis thaliana seeds. AB - In Arabidopsis thaliana, urease transcript levels increased sharply between 2 and 4 d after germination (DAG) and were maintained at maximal levels until at least 8 DAG. Seed urease specific activity declined upon germination but began to increase in seedlings 2 DAG, reaching approximately 75% of seed activity by 8 DAG. Urea levels showed a small transient increase 1 DAG and then approximately paralleled urease activity, reaching maximal levels at approximately 9 DAG. Urease inhibition with phenylphosphorodiamidate resulted in a 2- to 4-fold increase in urea levels throughout seedling development. Arginine pools (0-8 DAG) changed approximately in parallel with the urea pool. Consistent with arginine being a major source of urea, arginase activity increased 10-fold in the interval 0 to 6 DAG. Allopurinol, a xanthine dehydrogenase inhibitor, had no effect on urea levels up to 3 DAG but reduced the urea pool by 30 to 40% during the interval 5 to 8 DAG, suggesting that purine degradation contributed to the urea pool well after germination, if at all. in aged Arabidopsis seeds, there was correlation between phenylphosphorodiamidate inactivation of urease and germination inhibition, the latter overcome by NH4NO3 or amino acids. Since urease activity, urea precursor, and urea increase in young seedlings, and since urease inactivation results in a nitrogen-reversible inhibition of germination, we propose that urease recycles urea-nitrogen in the seedling. PMID- 7770521 TI - Organ-specific differential regulation of a promoter subfamily for the ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit genes in tomato. AB - The tomato (Lycopersicon esculentum) gene family for the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RBCS) has been investigated to determine the role of promoter regions and DNA-protein interactions in the differential organ-specific transcription of individual genes. Transgenic plants expressing RBCS-promoter-beta-glucuronidase fusion genes have confirmed that promoter fragments ranging from 0.6 to 3.0 kb of the RBCS1, RBCS2, and RBCS3A genes were sufficient to confer the temporal, organ-specific, and differential expression pattern observed for the endogenous genes. The individual temporal and organ-specific beta-glucuronidase enzyme activities closely reflect the qualitative and quantitative transcription activities of the respective RBCS genes, including the strongly reduced activity of RBCS3A (L.A. Wanner, W. Gruissem [1991] Plant Cell 3: 1289-1303). In particular, tissue-specific activity of all three promoters is similar in developing fruit, with high activity in the locular tissue and extremely reduced activity in the pericarp. This specific pattern of gene activity was further substantiated by in situ analysis of RBCS mRNA levels. Together, the data suggest an interesting correlation between RBCS gene activity and sink strength in different fruit tissues. DNA-protein interaction studies have revealed a novel fruit-specific DNA-binding protein called FBF that specifically interacts with a sequence element directly upstream of the G-box in the RBCS3A promoter. FBF binding thus correlates with the reduced activity of this promoter in developing tomato fruit, rendering it a candidate for a fruit-specific negative regulator of transcription in tomato. PMID- 7770522 TI - Characterization of the cell-wall polysaccharides of Arabidopsis thaliana leaves. AB - The cell-wall polysaccharides of Arabidopsis thaliana leaves have been isolated, purified, and characterized. The primary cell walls of all higher plants that have been studied contain cellulose, the three pectic polysaccharides homogalacturonan, rhamnogalacturonan I and rhamnogalacturonan II, the two hemicelluloses xyloglucan and glucuronoarabinoxylan, and structural glycoproteins. The cell walls of Arabidopsis leaves contain each of these components and no others that we could detect, and these cell walls are remarkable in that they are particularly rich in phosphate buffer-soluble polysaccharides (34% of the wall). The pectic polysaccharides of the purified cell walls consist of rhamnogalacturonan I (11%), rhamnogalacturonon II (8%), and homogalacturonan (23%). Xyloglucan (XG) accounts for 20% of the wall, and the oligosaccharide fragments generated from XG by endoglucanase consist of the typical subunits of other higher plant XGs. Glucuronoarabinoxylan (4%), cellulose (14%) and protein (14%) account for the remainder of the wall. Except for the phosphate buffer-soluble pectic polysaccharides, the polysaccharides of Arabidopsis leaf cell walls occur in proportions similar to those of other plants. The structure of the Arabidopsis cell-wall polysaccharides are typical of those of many other plants. PMID- 7770523 TI - The major tuber storage protein of araceae species is a lectin. Characterization and molecular cloning of the lectin from Arum maculatum L. AB - A new lectin was purified from tubers of Arum maculatum L. by affinity chromatography on immobilized asialofetuin. Although this lectin is also retained on mannose-Sepharose 4B, under the appropriate conditions free mannose is a poor inhibitor of its agglutination activity. Pure preparations of the Arum lectin apparently yielded a single polypeptide band of approximately 12 kD upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, N-terminal sequencing of the purified protein combined with molecular cloning of the lectin have shown that the lectin is composed of two different 12-kD lectin subunits that are synthesized on a single large precursor translated from an mRNA of approximately 1400 nucleotides. Lectins with similar properties were also isolated from the Araceae species Colocasia esculenta (L.) Schott, Xanthosoma sagittifolium (L.) Schott, and Dieffenbachia sequina Schott. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration of the different Araceae lectins have shown that they are tetrameric proteins composed of lectin subunits of 12 to 14 kD. Interestingly, these lectins are the most prominent proteins in the tuber tissue. Evidence is presented that a previously described major storage protein of Colocasia tubers corresponds to the lectin. PMID- 7770524 TI - Development and application of an in vivo plant peroxisome import system. AB - The purposes of this study are to develop an in vivo cell system that is suitable for the immunofluorescent detection of transiently expressed proteins targeted to plant peroxisomes and to determine whether a C-terminal serine-lysine-leucine (SKL) tripeptide, a consensus-targeting signal for mammalian peroxisomes, also targets proteins to plant peroxisomes. Protoplasts from mesophyll cells and from suspension-cultured cells initially were examined for their potential as an in vivo import system. Several were found suitable, but based on a combination of criteria, suspension-cultured tobacco (Nicotiana tabacum L. cv Bright Yellow 2) cells (TBY-2) were chosen. The tobacco cell extracts had catalase activity, and two polypeptides of approximately 55 and 57 kD specifically were detected on immunoblots with anti-cottonseed catalase immunoglobulins G as the probe. Indirect immunofluorescence microscopy with these immunoglobulins G revealed a punctate labeling pattern indicative of endogenous catalase localization within putative TBY-2 peroxisomes. The cells did not have to be completely converted to protoplasts for optimal microscopy; treatment with 0.1% (w/v) pectolyase for 2 h was sufficient. Microprojectile bombardment proved superior for transient transformation of the TBY-2 cells with plasmids encoding beta-glucuronidase, or chloramphenicol acetyltransferase (CAT), or CAT with an added C-terminal tripeptide (CAT-SKL). C-terminal SKL is a consensus, type 1, peroxisome targeting signal. Double indirect immunofluorescent labeling showed that CAT-SKL co localized with endogenous catalase. Non-punctate, diffuse localization of CAT without SKL provided direct evidence that the C-terminal SKL tripeptide was necessary and sufficient for targeting of CAT to plant peroxisomes. These data demonstrate the effectiveness of this peroxisome targeting signal for plant cells. PMID- 7770525 TI - Molecular features and mitochondrial import pathway of the 14-kilodalton subunit of cytochrome c reductase from potato. AB - The cytochrome c reductase complexes from fungi and mammals both contain a 14-kD protein (yeast, 14.4 kD; bovine, 13.4 kD) that does not directly participate in electron transfer but possibly is indirectly involved in the function of the complex and has a role in assembly of the multimeric enzyme. A subunit of comparable size was identified for the bc1 complex of higher plants. The 14-kD protein from potato (Solanum tuberosum) was specifically separated from the isolated protein complex in the presence of 6 M urea and is, therefore, assumed to be a peripheral component. Direct sequence analysis of the proteins from potato and wheat (Triticum aestivum) and isolation of corresponding cDNA clones for the subunit from potato revealed clear similarity to the equivalent proteins from yeast and bovine. The wheat 14-kD protein seems to occur in two isoforms. The 14-kD protein from plants is very hydrophilic, has a characteristic charge distribution, and contains no potential membrane-spanning helices. In vitro import of the radiolabeled 14-kD protein from potato into isolated mitochondria depends on the membrane potential across the inner mitochondrial membrane. The protein seems to lack a cleavable mitochondrial presequence, because it is not processed upon translocation. Possible intramolecular regions involved in targeting of the 14-kD protein to plant mitochondria are discussed. PMID- 7770527 TI - Rice cationic peroxidase accumulates in xylem vessels during incompatible interactions with Xanthomonas oryzae pv oryzae. AB - A cationic peroxidase, PO-C1 (molecular mass 42 kD, isoelectric point 8.6), which is induced in incompatible interactions between the vascular pathogen Xanthomonas oryzae pv oryzae and rice (Oryza sativa L.), was purified. Amino acid sequences from chemically cleaved fragments of PO-C1 exhibited a high percentage of identity with deduced sequences of peroxidases from rice, barley, and wheat. Polyclonal antibodies were raised to an 11-amino acid oligopeptide (POC1a) that was derived from a domain where the sequence of the cationic peroxidase diverged from other known peroxidases. The anti-POC1a antibodies reacted only with a protein of the same mobility as PO-C1 in extracellular and guttation fluids from plants undergoing incompatible responses collected at 24 h after infection. In the compatible responses, the antibodies did not detect PO-C1 until 48 h after infection. Immunoelectron microscopy was used to demonstrate that PO-C1 accumulated within the apoplast of mesophyll cells and within the cell walls and vessel lumen of xylem elements of plants undergoing incompatible interactions. PMID- 7770526 TI - Maize ribosome-inactivating protein (b-32). Homologs in related species, effects on maize ribosomes, and modulation of activity by pro-peptide deletions. AB - The ribosome-inactivating protein (RIP) from maize (Zea mays L.) is unusual in that it is produced in the endosperm as an inactive pro-form, also known as b-32, which can be converted by limited proteolysis to a two-chain active form, alpha beta RIP. Immunological analysis of seed extracts from a variety of species related to maize showed that pro/alpha beta forms of RIP are not unique to maize but are also found in other members of the Panicoideae, including Tripsacum and sorghum. Ribosomes isolated from maize were quite resistant to both purified pro- and alpha beta maize RIPs, whereas they were highly susceptible to the RIP from pokeweed. This suggests that the production of an inactive pro-RIP is not a mechanism to protect the plant's own ribosomes from deleterious action of the alpha beta RIP. RIP derivatives with various pro-segments removed were expressed at high levels in Escherichia coli. Measurement of their activity before and after treatment with subtilisin Carlsberg clearly identified the 25-amino acid intradomain insertion, rather than the N- or C-terminal extensions, as the major element responsible for suppression of enzymatic activity. A RIP with all three processed regions deleted had activity close to that of the native alpha beta form. PMID- 7770528 TI - The tomato Never-ripe locus regulates ethylene-inducible gene expression and is linked to a homolog of the Arabidopsis ETR1 gene. AB - Fruit ripening represents a complex system of genetic and hormonal regulation of eukaryotic development unique to plants. We are using tomato ripening mutants as tools to elucidate genetic components of ripening regulation and have recently demonstrated that the Never-ripe (Nr) mutant is insensitive to the plant growth regulator ethylene (M.B. Lanahan, H.-C. Yen, J.J. Giovannoni, H.J. Klee [1994] Plant Cell 6:521-530). We report here ethylene sensitivity over a range of concentrations in normal and Nr tomato seedlings and show that the Nr mutant retains residual sensitivity to as little as 1 part per million of ethylene. Analysis of ripening-related gene expression in normal and mutant ethylene treated fruit demonstrates that Nr exerts its influence on development at least in part at the level of ethylene-inducible gene expression. We have additionally used cloned tomato and Arabidopsis sequences known to influence ethylene perception as restriction fragment length polymorphism probes, and have identified a tomato locus linked to Nr that hybridizes to the Arabidopsis ETR1 gene at low stringency, suggesting the possibility that Nr may be homologous to ETR1. PMID- 7770529 TI - Polysaccharide composition of unlignified cell walls of pineapple [Ananas comosus (L.) Merr.] fruit. AB - The polysaccharides of cell walls isolated from the fleshy, edible part of the fruit of the monocotyledon pineapple [Ananas comosus (L.) Merr.] (family Bromeliaceae) were analyzed chemically. These cell walls were derived mostly from parenchyma cells and were shown histochemically to be unlignified, but they contained ester-linked ferulic acid. The analyses indicated that the noncellulosic polysaccharide composition of the cell walls was intermediate between that of unlignified cell walls of species of the monocotyledon family Poaceae (grasses and cereals) and that of unlignified cell walls of dicotyledons. Glucuronoarabinoxylans were the major non-cellulosic polysaccharides in the pineapple cell walls. Xyloglucans were also present, together with small amounts of pectic polysaccharides and glucomannans (or galactoglucomannans). The large amounts of glucuronoarabinoxylans and small amounts of pectic polysaccharides resemble the noncellulosic polysaccharide composition of the unlignified cell walls of the Poaceae. However, the absence of (1-->3,1-->4)-beta-glucans, the presence of relatively large amounts of xyloglucans, and the possible structure of the xyloglucans resemble the noncellulosic polysaccharide composition of the unlignified cell walls of dicotyledons. PMID- 7770530 TI - Elevated mRNA levels of the ribosomal protein L19 and a calmodulin-like protein in assimilate-accumulating transgenic tobacco plants. PMID- 7770531 TI - Nucleotide sequence of genomic DNA encoding the potato beta-1,3-glucanase. PMID- 7770532 TI - Nucleotide sequence of a cDNA encoding mitochondrial malate dehydrogenase from Eucalyptus. PMID- 7770533 TI - PZF, a cDNA isolated from Lotus japonicus and soybean root nodule libraries, encodes a new plant member of the RING-finger family of zinc-binding proteins. PMID- 7770534 TI - Nucleotide sequence of a Populus tremuloides gene encoding bispecific caffeic acid/5-hydroxyferulic acid O-methyltransferase. PMID- 7770535 TI - A spinach cDNA with homology to S-Adenosylmethionine decarboxylase. PMID- 7770536 TI - Nucleotide sequence of a rice cDNA encoding a homolog of the eukaryotic ribosomal protein S8. PMID- 7770537 TI - Isolation and characterization of a cDNA clone encoding a lectin gene from Agaricus bisporus. PMID- 7770538 TI - Two cDNA clones encoding isoforms of the beta-subunit of the general mitochondrial processing peptidase from potato. PMID- 7770539 TI - Cloning of an additional cDNA for the alternative oxidase in tobacco. PMID- 7770540 TI - Characterization of a cDNA encoding ribosomal protein S16 in rice. PMID- 7770541 TI - Nucleotide sequence of a cDNA encoding the ADP/ATP carrier from wheat (Triticum turgidum). PMID- 7770542 TI - High conservation among sequences encoding type-V thionins in wheat and Aegilops. PMID- 7770543 TI - Characterization of a cotton (Gossypium hirsutum L.) fiber mRNA (Fb-B6). PMID- 7770544 TI - Nucleotide sequence of Arabidopsis thaliana arginase expressed in yeast. PMID- 7770546 TI - Nucleotide sequence of a wheat chloroplastic phosphoglycerate kinase gene. PMID- 7770545 TI - Isolation, sequencing, and analysis of a 14-3-3 brain protein homolog from pea (Pisum sativum L.). PMID- 7770547 TI - Cloning and sequencing of a cDNA clone encoding the photosystem I PsaD subunit from Chlamydomonas reinhardtii. PMID- 7770548 TI - Differential down-regulation of epidermal growth factor receptors expressed in the metastatic variants of human lung cancer adenocarcinoma cell line DMS4C. AB - The metastatic variants of human lung adenocarcinoma cell line DMS4C were established by selection in vivo. Lung, brain, spleen and liver metastatic tumors derived from intracarotid inoculation of athymic BALB/c mice were collected, and their corresponding variant cell lines established. The epidermal growth factor (EGF) receptor expression of the parental cell line as well as the metastatic variant cell lines were investigated. 125I-labeled EGF binding assays showed that there were two types of EGF receptors in both parental and metastatic variants. Compared to DMS4C, the EGF binding capacities were found to be down-regulated by 70, 79, 85 and 89% for lung, spleen, liver and brain variant, respectively. The dissociation constants of spleen, liver and brain EGF receptors were distinct from that of the parental cell line. The EGF receptor autophosphorylation activity of lung variant was shown to be down-regulated as shown by immune complex kinase assay that corresponded to EGF receptor numbers whereas kinase activities of the liver, spleen and brain variants EGF receptors were completely abolished. However, the 170 kilodalton EGF receptor was shown to be unaltered during metastasis. The results indicated that, during metastasis progression, the proliferation of adenocarcinoma cells may have adopted a different growth regulation that is independent of EGF receptor kinase-modulated autocrine pathway. The result also implies that other oncogene may emerge as the major growth regulator for distant metastasis of adenocarcinoma cancer cells. This work provides a model for understanding tumor metastasis progression of human lung cancer. PMID- 7770549 TI - Gravity effect on lymphocyte deformation through cell shape change. AB - The effects on human cells (lymphocyte) immersed in a culture liquid under microgravity environment has been investigated. The study was based on the numerical simulation of the Morphology of human cells affected by the time dependent variation of gravity acceleration ranging from 10(-3) to 2 g(o) (g(o) = 9.81 m/s2) in 15 s. Both the free floating cells and the cells which came into contact with the upper and lower inclined walls imposed by the time-dependent reduced gravity acceleration were considered in this study. The results show that, when the gravity acceleration increased, the cell morphology changed from spherical to horizontally elongated ellipsoid for both the free floating cells and the stationary cells on the lower inclined wall while the cell morphology varied from spherical to vertically-elongated ellipsoid for the cells hanging on the upper inclined wall. A test of the deformation of human cells exposed to the variation of gravity levels, carried out in the KC-135 free fall aircraft, show that the results of experimental observations agree exactly with the theoretical model computation described in this paper. These results will be useful for study of the behavior and morphology of cells in space. PMID- 7770550 TI - Detection of Rickettsia tsutsugamushi specific DNA from the lymphocyte of patients by polymerase chain reaction. AB - Polymerase chain reaction was used to detect Rickettsia tsutsugamushi specific DNA from the lymphocytes of patients in the acute phase of the disease. The primers used in the PCR were based on the nucleotide sequences of gene encoding of the 56 kDa antigen of the Gilliam strain. The PCR product is a 78 bp fragment which can be hybridized by the 78 bp DNA probe of the Gilliam strain. Comparison of the results obtained by polymerase chain reaction, immunofluorescent assay and cell culture suggests that the polymerase chain reaction method is the most sensitive one among the three in diagnosis of scrub typhus. PMID- 7770551 TI - Assessment of heart wall motion: modified spatial modulation of magnetization for MR imaging. AB - This paper reports a new noninvasive method for detecting a regional myocardial infarction. The method consists of superimposing a magnetization grid onto different image planes of the human heart. In this study the spatial modulation of magnetization (SPAMM) in magnetic resonance imaging was modified to accommodate the use of a conventional clinical magnet. The percentages of circumferential shortening (PCS) and the percentages of wall thickening (PWT) during a cardiac cycle were estimated by measuring the amount of deformation of each grid from the end of the diastole to the end of the systole. A small data base was established on 10 subjects (6 normal volunteers and 4 patients). Patients with regional myocardial infarction, when monitored by the modified SPAMM investigation, showed smaller values of PCS and PWT in the areas where myocardial infarction was diagnosed by catheterization. The amount in decrement was directly proportional to the severity of the regional lesions. PMID- 7770552 TI - The center of ground reaction force during lifting. AB - The center locations of the ground reaction force were estimated when subjects assumed upright and bending postures as well as when they lifted at low and high speeds. Ten subjects participated in this study and were instructed to assume two postures and to perform two liftings sequentially in a random order. The center locations of the ground reaction force were calculated using a Computerized Dyno Graphic system (INFOTRONIC). The center of the ground reaction force in the full bending posture had a more anterior location than it did in the upright standing posture. When measured during the lifting activity, the center of the ground reaction force shifted forward and then backward during the whole activity. The center location shifted to a more anterior location during high-speed lifting than it did during low-speed lifting. PMID- 7770553 TI - Suicide in Quebec, 1951-1986. AB - Data from Fortier, et al. (1989) were reanalysed using multiple regression. While birth and divorce rates were significantly associated with both male and female suicide rates, unemployment rates and cirrhosis death rates were associated only with male suicide rates. PMID- 7770554 TI - Toward a new approach to schizophrenic psychosis. AB - The author proposes a classifying principle for the various clinical aspects of schizophrenia. It is based on the hypothesis that thinking processes are carried on as the three temporal conditions of the experience (continuous, discontinuous and successive, and reversible or simultaneous) whose combination structures sane thoughts. Mental symptoms are proposed as indexed to the particular anomaly of one of those three components: disruption to the lack of simultaneity, hallucination to the lack of continuity, delusion and misinterpretation to the lack of successivity. Other symptoms (deficit, withdrawal, stereotypy) are reactional to one of the prior mechanisms. PMID- 7770555 TI - Uric acid levels and severity of aggression. PMID- 7770556 TI - Parents' perceptions of their adolescence: implications for parent-youth conflict and family satisfaction. AB - This study examined the relation between parents' perceptions of "storm and stress" in their own adolescence and their current relationships with their children. A sample of 121 adolescents and their parents (106 mothers) were surveyed. Analysis indicated that over 48% of these parents viewed their adolescence as being stormy and stressful. Parents who experienced greater storm and stress as youth had more conflict in their relationships with their children and were less satisfied with their families. Implications for intergenerational theory and family intervention are presented. PMID- 7770557 TI - Internal reliability and convergent validity of the Depression-Happiness Scale with the General Health Questionnaire in an employed adult sample. AB - The aim of this study was to investigate the internal reliability and convergent validity of the 1993 McGreal and Joseph Depression-Happiness Scale. Internal reliability was satisfactory and higher scores on the scale were associated with lower scores of 60 working adults on the General Health Questionnaire of Goldberg and Williams. PMID- 7770558 TI - MMPI scores of female victims. AB - Samples of MMPIs of women who were victims of abuse or manifested a Posttraumatic Stress Disorder were drawn from two private practice settings, one urban and one in a small town. Each PTSD sample included 21 persons. For comparison, two contrast samples of 15 persons each were drawn from the same populations. A cut off point of T = 65 for PK yielded a 69% hit rate for classifying PTSD and contrast subjects. Since scores on PS and PK were so highly correlated, no independent analyses were warranted. Although the PTSD group yielded a more elevated mean profile, there were no characteristic 2-point codes. Therefore, PK is more useful in identifying Posttraumatic Stress Disorder than either profile elevation or configuration. PMID- 7770559 TI - Naloxone blocks learned helplessness in the slug (Limax maximus). PMID- 7770561 TI - Open-area seclusion in the long-term treatment of aggressive and disruptive psychotic patients, an introduction to a ward procedure. AB - The clinical rationale and procedure of "open-area seclusion" as a treatment modality with psychotic patients is presented. This standard procedure was originally introduced as an alternative to arbitrary measures in response to aggressive and disruptive behavior. The seclusion area is locked, but the patient is never locked up alone in any single room. The method of open-area seclusion is composed of four overlapping phases: (1) assisting the patient to the seclusion area, (2) time for a "calming down" process, (3) debriefing, and (4) reintegration. Verbal confrontation is central in enhancing the secluded patient's reality-testing, for reinforcing responsibility for one's own behavior, and for encouraging alternative problem-solving. A step-by-step description of the procedure of open-area seclusion is presented and illustrated by a case history. PMID- 7770560 TI - Use of the Lollipop Test as a predictor of California Achievement Test scores in kindergarten and transitional first-grade status. PMID- 7770562 TI - Relationship of response-set differences on Beck Depression Inventory scores of undergraduate students. AB - The relationship of a ruminating and a distracting response style upon severity of depression and on gender were investigated. The Ways of Coping Questionnaire was modified to include ruminating and distracting scales and administered to 91 undergraduate students who also completed the Beck Depression Inventory. It was hypothesized that (a) regardless of gender, people who ruminate would have greater rated severity of depression than people who distract themselves; (b) women ruminators would show higher rated severity of depression than women distractors; and (c) female and male ruminators would show the same ratings on severity of depression. A set of t ratios was computed for mean differences between the groups. An analysis of variance for response style x gender was also done with the women and men classified as ruminators. The results conformed to the predictions for women but not for men. PMID- 7770563 TI - MCMI-II profiles and typologies for patients seen in marital therapy. AB - The Millon Clinical Multiaxial Inventory-II profiles of 145 patients in marital therapy, seen in a private-practice outpatient setting, were subjected to a hierarchical cluster analysis. Four distinct clusters were found (MCMI-II Codetypes 58B4, 8A6B8B5, 3217, and 37). Each of these clusters suggested different therapeutic goals. There were some scale differences by gender, with women tending to score higher on the Dependent Scale. We argue that private practice settings generate a wealth of data which can be taken from such files and used to address empirical questions. PMID- 7770565 TI - Ireland: gender, psychological health, and attitudes toward emigration. AB - Ireland is experiencing one of the highest periods of emigration in its history. The current study collected demographic and psychological data on 203 Irish men and women in Ireland and in Northern Ireland, including measures of self-esteem, depression, attitudes toward immigration, and expectancies of emigration. Analysis indicated that approximately 81% of this Irish sample are considering emigration; however, the prospect of emigration is psychologically experienced differently by men and women. While there were no significant differences over all in scores on self-esteem between Irish men and women, men who contemplated emigration reported higher self-esteem scores, and women contemplating emigration reported lower self-esteem scores (relative to those who had no plan to emigrate). In addition, women who contemplated emigration had higher depression scores than women who did not contemplate emigration. This pattern was not evident for men. These results indicate that psychologically women view the prospect of emigration less positively than men. PMID- 7770564 TI - Temporal stability of psychophysiological stress profiles: a re-analysis using intraclass correlation coefficients. AB - This is a re-analysis of data from a previous study which examined the temporal stability of three psychophysiological responses [frontal electromyographic activity (EMG), hand surface temperature, and heart rate]. Each response was recorded on 64 subjects over four sessions, each of which consisted of a 20-min, adaptation period, a baseline condition, and two stressors (one cognitive, the other physical). Rather than using Pearson product-moment correlations, as nearly all psychophysiological test-retest reliability studies have, we have now analyzed the data using intraclass correlation coefficients. This type of correlation allows one to incorporate more than two test-retest values on the same subjects. Analysis indicated that, with the exception of EMG during the physical stressor, the absolute values of the responses had quite significant reliability (.70 or greater). Treating the responses as relative measures (percent change from baseline or simple change scores from baseline) produced smaller and frequently less stable coefficients. It is concluded that statistical estimates of psychophysiological response reliability are functions of the design and particular reliability analysis employed. PMID- 7770566 TI - Measures of treatment outcome of depression: an effect-size comparison. AB - Meta-analytic studies of the values of various measures of the outcome of antidepressive treatment have consistently shown that different scales produce different patterns of progress for the same patients, but results have differed somewhat in other respects. The present results suggest that these problems are probably related to use of different scales emphasizing different aspects of depression. PMID- 7770567 TI - Improving mental fitness reports of candidates for police officer and fire fighter. AB - On the basis of 18 years of experience on the Medical Review Panel of the New Jersey Department of Personnel, the author points out some shortcomings commonly observed in psychological/psychiatric evaluative reports on mental fitness of police officer and fire fighter candidates. Each shortcoming is noted under one of two headings, i.e., routine information or inferences. PMID- 7770569 TI - Community context and the underutilization of mental health services by minority patients. AB - An organization applying the principles of "community context" had 20 dropouts among 111 African American and Hispanic patients in its mental health services. Its sister organization applying conventional psychiatric service approaches had 114 dropouts among 167 African American and Hispanic patients. PMID- 7770568 TI - FIRO-B: the power of love and the love of power. AB - Factor analysis of FIRO-B data obtained from new software product teams had led to a reformulation of Schutz's ideas on team compatibility. The concept of Group Warmth as a derivative of the FIRO-B Inclusion and Affection scales was developed and shown to be related to the commercial effectiveness of teams. In a like manner, the FIRO-B constructs of Control-Expressed and Control-Wanted were explored through concurrent factor analysis of 16 PF data. A new interpretation has been given to both FIRO-B Control scales, namely, Assertive-Impulsive. PMID- 7770570 TI - Sexual behavior and telling the truth on questionnaires. PMID- 7770571 TI - Relationship between the Bracken Basic Concept Scale and the Differential Ability Scales with an at-risk sample of preschoolers. AB - This study investigated the relationship between the Bracken Basic Concept Scale and the Differential Ability Scales with 35 at-risk preschoolers between the ages 3-6 and 5-11. A Pearson product-moment correlation coefficient of .70 was obtained between the Bracken Basic Concept Scale Total Test scores and the General Conceptual Ability scores of the Differential Ability Scales. This association supports the use of the Bracken scale to predict intelligence if replicated with a larger sample and specific handicaps. In addition, support for the administration of the more brief Bracken School Readiness Composite compared to using the Bracken Total Test score in the prediction of the Differential Ability Scales General Conceptual Ability score was found. PMID- 7770572 TI - Gender and depression in undergraduates: a comment. PMID- 7770573 TI - Training effects of one academic year on instructional values of MA students in confluent education and counseling psychology. PMID- 7770574 TI - Chronic pain and depression: is social support relevant? AB - This study examined the relationship between social support and depression for 70 patients with chronic back pain. We also explored whether the family environments of these patients related to depression and whether the patients' depression predicted outcome subsequent to involvement in a functional restoration program. The patients completed a battery of psychological questionnaires to assess depression, social support, and family environment. Outcome of a rehabilitation program was measured in terms of physical gains, vocational gains, and progress made toward program goals. Analysis indicated that the 25 depressed and 23 nondepressed patients differed as to perceived social support and quality of family environment; however, no association was found between depression and rehabilitation outcome. Implications for family interventions are discussed. PMID- 7770575 TI - Animal rights activism and animal welfare concerns in the academic setting: levels of activism and the perceived importance of research with animals. AB - Past research suggests that public support for the use of animal models as means to improve the human condition is present but many individuals have expressed ambivalence. In the present study, various sectors of the academic community (students and faculty) as well as the general population, were surveyed to assess their positions on the need for, and value of animal research, the value of psychological research in which animals are employed, and the respondents' consummatory habits. The results suggested that more information needs to be provided about the role of animal experimentation, including a discussion of the benefits produced by using animals to answer psychological questions. PMID- 7770576 TI - Self-reported high-risk behavioral history of HIV positive prison inmates. AB - 30 male HIV positive prison inmates tended to deny high-risk behavior for infection, most notably homosexuality. The public health implications are that the veracity of such denial should not be assumed. PMID- 7770577 TI - Inner speech as a cognitive process mediating self-consciousness and inhibiting self-deception. AB - The cognitive processes which mediate self-consciousness are unknown. although Morin and others have suggested that inner speech may mediate self-consciousness. We developed a questionnaire which measures the extent to which one talks to oneself about oneself. As expected, the correlation between inner speech and self consciousness was significant. A German version of the 1979 self-deception questionnaire by Sackeim and Gur correlated negatively with the scores on inner speech, suggesting the validity of the questionnaire. We also replicated the negative association between depression and self-deception in a different culture. PMID- 7770578 TI - Attitudes of women toward homosexual behavior as a function of veteran status. PMID- 7770579 TI - Preliminary data on a relation between self-talk and complexity of the self concept. AB - Recent empirical work in social cognition suggests that in building a self concept people make inferences about themselves based on overt behavior or private thoughts and feelings. This article addresses the question of how, exactly, people make these inferences about themselves and raises the possibility that they do so through self-talk. It is proposed that the more on talks to oneself to construct a self-image, the more this image will gain coherence and sophistication. A correlational study was conducted to explore the relation between richness of the self-concept (using the W-A-Y) and natural disposition to talk to oneself (using a pilot questionnaire). A moderate but positive correlation of .30 is obtained. The article concludes with clinical implications. PMID- 7770580 TI - The Behavioral Academic Self-Esteem Scale with preschoolers. AB - 15 teachers completed the Behavioral Academic Self-Esteem Scale (alpha = .93) for 71 preschoolers. Teachers rated self-esteem positively. Three factors were identified, confident approach, adaptability to routines, and dealing with failure/frustration. PMID- 7770581 TI - Chronic obstructive pulmonary disease and symptoms related to depression in elderly persons. AB - In a community study, 61 men and 21 women with mild to severe chronic obstructive pulmonary disease (COPD) were compared with age- and sex-matched controls (183 men and 63 women) to identify and analyze the associations between the occurrence of COPD and depressive symptoms, the occurrence of previous or current psychiatric disorders, the use of psychiatric drugs, and satisfaction with one's marital relationship. In men, no associations between COPD and the above factors were found. More women with COPD than controls reported feelings of dissatisfaction with life. The female patients also tended to be less satisfied with their marital relationship than the controls. Multivariate analysis showed that this disease in women was associated with disability (odds ratio 3.25, 95% confidence interval 1.17-9.06), feelings of dissatisfaction with life (odds ratio 3.56, 95% confidence interval 1.23-10.34), and low satisfaction with one's marital relationship (odds ratio 3.23, 95% confidence interval 1.10-9.47). These results seem to suggest that elderly female patients with COPD have more mental health problems than male patients and these will require more attention from the primary care providers. PMID- 7770582 TI - Some comments on the Gough Socialization Scale. PMID- 7770583 TI - Two investigations of the validity of the WISC-III. AB - Two studies were conducted in which the validity of the WISC-III was investigated. In Study 1, WISC-R and WISC-III IQs were correlated for a sample of 53 students, who, although originally meeting criteria for a disability category through use of the WISC-R, did not meet eligibility criteria upon reevaluation with the WISC-III. Corrected correlations between IQs were high, ranging from .80 to .87, and were comparable to figures reported in the WISC-III manual. Consistent with the WISC-III manual, WISC-III IQs were 8, 5, and 7 points lower than the WISC-R Full Scale, Verbal, and Performance IQs, respectively. In Study 2, the criterion validity of the WISC-III with the WRAT-R Reading, Spelling, and Arithmetic subscales and with the PPVT-R was investigated for a sample of 32 students with mental retardation. The WISC-III IQs and PPVT-R scores were highly correlated, sharing between 64 to 76% of variance. Correlations between WISC-III IQs and scores on the WRAT-R Reading and Arithmetic subscales were moderate. Surprisingly, the WISC-III IQs were not related to the WRAT-R Spelling scores. Implications of both studies for assessment specialists are discussed. PMID- 7770584 TI - The type 2 construct and its relation to coronary heart disease. AB - The main aim of this study was to scrutinize the link postulated in 1988 between the Type 2 construct of Grossarth-Maticek, Eysenck, and Vetter and the incidence of coronary heart disease. Self-report data were collected from 58 men who had suffered an infarct, had been hospitalised, and had later enrolled at a physical outpatient clinic as well as from a randomly assigned control group of 70 men. Analysis showed that the Type 2 scores in the infarct group did not differ significantly from those of the control group or from measures taken immediately after an acute myocardial infarction and measures taken 3 months later. The results do not support the hypothesis of a strong association between coronary heart disease and Type 2 scores. PMID- 7770585 TI - Race and crime: international data for 1989-1990. AB - The rate of murder, rape, and serious assault per 100,000 members of the population was tabulated for 76 countries from the 1989-1990 International Crime Statistics published by INTERPOL. Following previous research the countries were grouped into the three major populations of Asian, Caucasian, and African. Consistent with previous evidence the results showed that crime rates are highest for countries with predominantly African populations, lowest for those with predominantly Asian populations, and in-between for those with predominantly Caucasian populations. The 23 countries with predominantly African populations reported twice as high a rate for each type of crime as the 41 countries with predominantly Caucasian populations and over three times as high a rate as the 12 countries with predominantly Asian populations. Summing the crimes gives figures, respectively, of 240, 75, and 32 violent crimes per 100,000 population. PMID- 7770586 TI - Survey of the nature and prevalence of patients' noncompliance and implications for intervention. AB - The problem of patients' noncompliance is discussed, noting possible biases in estimates of prevalence (18 to 82%) which may overestimate compliance rates and frequent failure to define conditions constituting compliance. This survey obtained information on the nature and incidence of noncompliance from a "healthy," Census-based, sample (n = 148), age 20 to 79 years. Data were examined to identify relationships among variables in compliance and demographic characteristics. The typical household had 3.9 prescribed drugs, 46% of respondents chose generic products, 54% preferred tablets or pills, and 69% cited physicians as their primary information source on medications. Rates were identified for obtaining and using all prescribed drugs and following frequency and dose instructions for prescriptions. Full compliance was reported by 25%, and seriousness of illness was the most important factor cited as an influence. PMID- 7770587 TI - Belief in lunar effects on human behavior. AB - Questionnaires sent to 325 people indicated that 140 people (43%) held the personal belief that lunar phenomena alter individual behavior. Specifically, mental health professionals (social workers, master's clinical psychologists, nurses' aides, LPNs) held this belief more strongly than other occupational groups. PMID- 7770588 TI - Attachment anxiety and reciprocity as moderators of interpersonal attraction. AB - In integrating the interpersonal domains of attraction, perceived reciprocity, and attachment security, the prediction was made that positive interpersonal feedback (reciprocity) would lead to a greater increase in attraction ratings for anxiously versus securely attached individuals and, correspondingly, negative interpersonal feedback would cause a greater diminution in attraction ratings for anxiously versus securely attached individuals, with neutral feedback having no differential effect. For a sample of 154 college students, these predictions as well as an unanticipated gender finding were supported. The findings and clinical implications concerning the susceptibility of anxiously attached individuals to positive interpersonal cues are discussed in terms of a compromised sense of the availability and responsiveness of attachment figures. PMID- 7770589 TI - Self-esteem, stress, and depression among graduate students. AB - In a study of 29 graduate students, self-ratings of stress correlated with low scores on self-esteem but were not related to an objective indicator of actual stress. Both self-rated stress and low self-esteem scores were related to scores on depression, with a weak interaction effect. PMID- 7770590 TI - Assessment of subjective distress by patients' self-report versus structured interview. AB - Comparison was made of symptom and behavior scores obtained by structured interview versus self-report using the Behavior and Symptom Identification Scale. Psychiatric hospital admissions were randomly assigned to 1 of 3 assessment groups, structured interview, self-report, or choice of procedure. Analysis indicated that patients in the self-report group reported significantly greater difficulty on 1 of 5 dimensions assessed by the scale. The results suggest that a self-report questionnaire form of the measure is a viable alternative to the structured interview. PMID- 7770591 TI - Factor analysis of the Center for Epidemiological Studies-Depression Scale. AB - The Center for Epidemiological Studies-Depression Scale is one of the most popular instruments for survey work with the general population. A 1993 study by Thorson and Powell reported a 5-factor solution. The present study was undertaken to replicate these findings; however, factor analysis with varimax rotation based on the responses of 187 students yielded 4 factors of depressed affect, somatic disturbance, positive affect, and interpersonal difficulties. Although these data do not replicate the 5-factor work of Thorson and Powell, they do largely confirm the previous research. PMID- 7770592 TI - Birth order and family size: influences on adolescents' achievement and related parenting behaviors. AB - The purposes of this study were to confirm birth-order and family-size differences in achievement, to confirm birth-order and family-size differences in parenting, and to examine whether parenting style and parental involvement serve as mediators of birth-order and family-size differences in achievement. Subjects were 195 ninth-grade boys and girls and their parents from urban, suburban, and rural communities in the southeast and the midwest. Questionnaire measures of adolescents' and parents' perceptions of parenting style and parental involvement were used. Birth-order and family-size differences were found in adolescents' achievement and perceptions of parenting style and parental involvement but not in parents' perceptions of parenting. However, these parenting characteristics did not mediate the differences seen in achievement by birth order and family size. Implications of these findings are discussed. PMID- 7770593 TI - Knowledge of basic emotions in adolescent and adult individuals with autism. AB - An experiment was carried out in which 30 adolescent and adult patients with autism and 30 age- and IQ-matched Down syndrome patients were instructed to choose one of the chocolates that were hanging near four pictures displaying facial expressions of basic emotions (fear, anger, happiness, and sadness). As predicted, most of the Down syndrome patients took the chocolate near the happy face picture. Unexpectedly, however, autistic patients made more responses to the fearful face picture. Also, Down syndrome patients were more capable of naming the four basic emotions than autistic patients. PMID- 7770594 TI - Retroductive reasoning in a proposed subtype of partial seizures, evoked by limbic "kindling". AB - This analysis provides a specific example of the generally applicable process of creative delineation of a novel pattern while searching for an explanatory hypothesis for puzzling observations. In so doing, the neglected retroductive form of inference or abduction was used. Central to such a process is the delineation of a specific "generative mechanism" capable of uniting and explaining heretofore unexplained phenomena. Herein the neurophysiologically known mechanism of limbic seizure "kindling" is offered as a unifying explanation for a dozen bizarre phenomena, proposed as a new subtype of partial seizures, "Limbic Psychotic Trigger Reaction." This new syndrome has been proposed over 15 years in 17 male social loners. Upon encounter with an individualized stimulus, which revived in memory prior moderately hurtful experiences, these men suddenly committed motiveless, unplanned acts with flat affect, transient psychosis and autonomic arousal, showing no quantitative impairment of consciousness and so without memory loss for their perplexing homicidal acts (13 cases), firesetting (3 cases), or bank robbery (1 case). Events occurred in three phases reminiscent of seizures: (1) aura-like puzzlement, (2) transient ictus with a limbic release of predatory or defensive aggression (circa 20 min.), and (3) postictal inefficient actions, implicating a transient frontal lobe system dysfunction secondary to the limbic hyperactivation. The 17 men were of diverse backgrounds, but all without history of prior violence or severe emotional trauma. Seven of 17 had some abnormal tests at some time during their lives and eight known histories of typically overlooked closed-brain injury. Brain damage may facilitate seizure "kindling" but has been traditionally observed in mammals and in a few humans without such damage. PMID- 7770595 TI - Examining the relationship between Machiavellianism and paranoia. AB - To investigate the relationship between Machiavellianism and paranoid tendencies we administered the Mach IV scale and Fenigstein and Vanable's Paranoia scale to 150 students enrolled in 4 sections of a course, Introduction to Psychology, at a university in the Middle South. Scores on the 2 were significantly and positively correlated (Pearson r = .50). Men had a significantly higher mean score on Machiavellianism than women. Although men obtained a higher mean on the Paranoia scale than women, the difference was not statistically significant. Implications are discussed. PMID- 7770596 TI - Maintenance of weight loss after a very-low-calorie diet involving behavioral treatment. AB - The long-term effects of a very-low-calorie diet coupled with behavioral therapy were studied for 209 subjects. Although a low goal weight, frequent calorie counting and exercise, and a later age of onset of obesity predicted a low relative weight, most respondents had regained most of the weight they had lost. PMID- 7770597 TI - The Rotterdam Daytime Sleepiness Scale: a new daytime sleepiness scale. AB - A new daytime sleepiness scale was constructed on the basis of interviews with 96 apnea patients (the Rotterdam Daytime Sleepiness Scale) and included three subscales of Global Evaluation, Behavioral Impact, and Affected Life Domains. The scale showed satisfactory convergent and discriminant validity. PMID- 7770598 TI - A quick screening test of competency to stand trial for defendants with mental retardation. AB - 19 terms and concepts from evaluations of competency to stand trial of 55 defendants with mental retardation were rated to examine whether a quick screening test could be devised that would differentiate those who were judged competent or not competent. A multiple regression and discriminant analysis gave four items that yielded maximum predictability (R = .84): court strategy, plead, testify, and jury. Guilty, trial, and prosecutor were also significantly more difficult for those who were not competent than those who were. PMID- 7770599 TI - Risk factors for drug abuse in Pakistan: a replication. AB - While a number of risk factors have been identified for drug abuse in the United States, little evidence is available about such factors in some other counties. Among these latter is Pakistan, a nation in which heroin addiction is a major problem. The present study was done to examine those psychosocial characteristics which differentiated 60 heroin addicts from 60 nondrug-using controls in Pakistan. Most of the drug-abuse factors identified earlier were significant in Pakistan as well. Applying cut-off scores previously established for each of 9 variables, the relationship between drug status and number of factors at risk was also examined. Over 98% of the addicts were at risk for five or more factors; only 15% of controls were at risk for 5 variables and none exceeded 5. Precursors for abuse appear to cut across cultural lines. The high-risk individual in Pakistan, as in the United States, is one with ready access to drugs and the social inducements to use them while lacking bonds with societal institutions or value systems which might mitigate against drug use. Because several of the risk factors represent deep and long-standing aspects of the addict's personality, both prevention and treatment confront formidable difficulties. PMID- 7770600 TI - Effects of ibogaine on responding maintained by food, cocaine and heroin reinforcement in rats. AB - The effects of ibogaine (40 and 80 mg/kg, i.p.), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, i.p.) given 60 min before the start of the session resulted in a 97% decrease in the number of ratios completed under the food reinforcement schedule and resulted in a decrease in responding the following day. Neither 40 mg/kg ibogaine given 60 min prior to the session nor 80 mg/kg given 24 h before the session suppressed responding maintained by cocaine infusions (0.33 mg/infusion). Pretreatment with 80 mg/kg ibogaine either 60 or 90 min prior to the session suppressed cocaine self-administration on the day it was administered and the longer pretreatment continued to suppress responding for 48 h. Responding maintained by heroin (18 micrograms/infusion) was the most sensitive to the effects of ibogaine. Both 40 and 80 mg/kg ibogaine resulted in an almost complete suppression of responding following a 60-min pretreatment period. Responding maintained by heroin returned to control levels the day following the administration of ibogaine. PMID- 7770601 TI - Response-dependent versus response-independent presentation of cocaine: differences in the lethal effects of the drug. AB - The drug self-administration paradigm is routinely used to assess the abuse liability of psychoactive compounds. Investigations of the behavioral effects of drug use, however, often involve the response-independent (experiment-delivered) administration of the compound. It is frequently assumed that response independent presentation of a compound has the same effects as response dependent deliveries. The present study examined directly the effects of response-dependent (self-administered) versus response-independent (experimenter-delivered) administration of cocaine on food intake and lethality. Littermate triads were exposed to either cocaine (0.33 mg/infusion) or saline using a yoked-box procedure. One member of the triad self-administered the drug under a fixed-ratio 2 schedule. The other two rats received response-independent infusions of either cocaine or saline. Groups of triads were exposed to two different cocaine access conditions. Daily sessions were terminated after 6 h for one group and after the delivery of 80 infusions for the other. The mean number of infusions delivered each session was 47 (+/- 12) and 70 (+/- 11), respectively, for the 6-h and 80 infusion condition. Under the 80-infusion condition, response-independent infusions of cocaine resulted in a significantly higher rate of mortality compared to littermates self-administering identical amounts of the drug. A fewer number of deaths occurred under 6-h condition; however, only rats exposed to response-independent infusions died under both access conditions. These data indicate that the presence or absence of response dependency can profoundly alter the lethal effects of cocaine. PMID- 7770602 TI - Prepulse inhibition of the acoustic startle reflex using visual and auditory prepulses: disruption by apomorphine. AB - The amplitude of the acoustic startle reflex can be reduced reliably when preceded at short intervals by a weak stimulus (prepulse) which itself does not elicit startle. The magnitude of this prepulse inhibition effect is attenuated by several dopamine agonists, such as apomorphine, especially when there is a relatively small difference between the intensity of the prepulse and the intensity of the background noise over which the prepulse is superimposed. One goal of the present experiment was to test the generality of this disruptive effect of apomorphine on prepulse inhibition by using either an auditory prepulse that included both a change in intensity and a change in frequency relative to the background noise or a visual prepulse stimulus. Apomorphine reduced auditory prepulse inhibition when induced by a small change in stimulus intensity, but not when induced by a change in both intensity and frequency. Apomorphine consistently reduced visual prepulse inhibition with a complete blockade at 100 ms test interval. However, it did not fully block the usual reduction in startle onset latency or even attenuate the increase in startle amplitude when a visual prepulse was presented 5, 10 or 15 ms before the startle stimulus. Consistent with conclusions from other laboratories using auditory prepulse inhibition, these data suggest that apomorphine did not prevent the animal from detecting prepulse presentation under conditions where the drug completely blocked prepulse inhibition. Moreover, they indicate that the blockade of prepulse inhibition by apomorphine was independent of prepulse modality, adding generality to the original finding. Visual prepulse inhibition may be a useful alternative procedure for evaluating the effects of drugs on this attentional process. PMID- 7770603 TI - Differential anti-parkinsonian effects of benzazepine D1 dopamine agonists with varying efficacies in the MPTP-treated common marmoset. AB - In common marmosets systemically treated with MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), the behavioural effects of benzazepine D1 dopamine (DA) agonists with full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393, SKF 75670 and SKF 83565) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) activity were investigated. The benzazepine derivatives, with the exception of SKF 82958 (8 fold D1 DA receptor selectivity), demonstrated high D1 DA receptor affinity and selectivity (approximately 100 fold or more) in rat striatal homogenates. Administration of MPTP in marmosets induced locomotor hypoactivity, rigidity and motor disability. SKF 38393 (7,8-dihydroxy-1-phenyl 2,3,4,5-tetrahydro-1H-3- benzazepine) and SKF 75670 (3-CH3 analogue) further reduced locomotor activity (by -70 to -80%) and increased motor disability (by +22 to +67%) in these animals. SKF 83565 (6-Cl, 3-CH3, 3'-Cl analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) had only a slight effect on locomotor activity but decreased motor disability at high doses (-46 to -60%). In contrast, SKF 83959 (6 Cl, 3-CH3, 3'-CH3 analogue) and SKF 80723 (6-Br analogue) produced pronounced increases in locomotion (6-10 fold) and a reversal in motor disability (by -64 to -77%). Oral activity, consisting largely of abnormal, 'dyskinetic' tongue protrusions and vacuous chews, was increased in animals treated with SKF 38393, SKF 83565, SKF 82958 and more especially with SKF 80723 and SKF 83959. Grooming was increased with SKF 82958 and more especially with SKF 80723 and SKF 83959. In contrast, quinpirole (D2 DA agonist), reversed the MPTP-induced motor deficits in the marmoset, with no effect on grooming and oral activity. The present findings further demonstrate the antiparkinsonian actions of some D1 DA agonists in MPTP treated primates. However, in general the behavioural effects of benzazepines failed to correlate with either their D1 DA receptor affinity/selectivity or their efficacy in stimulating adenylate cyclase (AC) activity. These observations further implicate a behavioural role for D1 DA receptors uncoupled to AC and/or a role for extrastriatal D1 DA receptors in mediating the behavioural response to D1 DA agonists. PMID- 7770604 TI - The differential behavioural effects of benzazepine D1 dopamine agonists with varying efficacies, co-administered with quinpirole in primate and rodent models of Parkinson's disease. AB - The effects of co-administration of quinpirole with benzazepine D1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinson's disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl 2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Co-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Co administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D1 DA receptors not linked to AC. PMID- 7770605 TI - The impact of long-term vitamin supplementation on cognitive functioning. AB - The possibility that the taking of vitamin supplements may influence cognitive functioning was explored. One hundred and twenty-seven young healthy adults took either ten times the recommended daily dose of nine vitamins, or a placebo, under a double-blind procedure, for a year. After 12 months better performance on two measures of attention was found in females who had taken the vitamin supplement, even though the blood status of nine vitamins reached a plateau after 3 months. The use of regression equations demonstrated the association between improved thiamin status and improved performance on a range of measures of cognitive functioning in females rather than males. Although it was not possible to establish the reason for a beneficial response in females rather than males, the evidence that females respond differently to dietary factors was discussed. PMID- 7770606 TI - Profile of action of 5-HT3 receptor antagonists, ondansetron and WAY 100289, in the elevated plus-maze test of anxiety of mice. AB - The effects of ondansetron (0.001-0.1 mg/kg) and the novel 5-HT3 receptor antagonist, WAY 100289 (0.01-10.0 mg/kg), on anxiety were examined in male mice using an ethological version of the elevated plus-maze paradigm. This procedure involves scoring specific aspects of defensive behaviour in addition to the more usual spatiotemporal measures. Results show that, at the doses tested, neither compound produced a behavioural profile consistent with anxiety reduction. Indeed, the lowest dose of ondansetron (0.001 mg/kg) produced some behavioural trends more typically associated with mild anxiety enhancement. Data are discussed in relation to the enigmatic effects of 5-HT3 receptor antagonists in animal models of anxiety. It is suggested that the large within- and between-test variability observed with these compounds may indicate an action on mechanisms other than anxiety. PMID- 7770607 TI - Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior. AB - The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors. PMID- 7770609 TI - Comparative anterograde amnestic and anticonvulsant effects of two types of NMDA receptor antagonists: MK-801 and HA-966. AB - The anterograde amnestic effects of non-competitive NMDA antagonists MK-801 and HA-966 on classic fear conditioning in goldfish (Carassius auratus) were examined in a series of experiments. Experiments 1 and 2 contrasted the anterograde amnestic effects of MK-801, (+)HA-966, and (-)HA-966. Experiment 3 examined the effects of MK-801 and (+)HA-966 on the expression of conditioned responses. Experiments 4 and 5 investigated whether the potency of MK-801, (+)HA-966 or ( )HA-966 in blocking NMDA-induced convulsions paralleled their potency in producing amnesia. The results showed that MK-801 was more potent than (+)HA-966 in producing anterograde amnesia and impairing expression, while (-)HA-966 did not produce anterograde amnesia. The anticonvulsant potency of MK-801, (+)HA-966, and (-)HA-966 paralleled their amnestic potency. These findings suggested that MK 801 and (+)HA-966 produced anterograde amnesia by their specific antagonism of the NMDA receptor complex. PMID- 7770611 TI - Chronic treatment with fluvoxamine by osmotic minipumps fails to induce persistent functional changes in central 5-HT1A and 5-HT1B receptors, as measured by in vivo microdialysis in dorsal hippocampus of conscious rats. AB - This study investigated the alterations of the 5-HT1A and 5-HT1B autoreceptor function following chronic treatment with fluvoxamine using osmotic minipumps. The 5-HT1A and 5-HT1B autoreceptor function were studied using microdialysis in the dorsal hippocampus. The effect of the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, SC) and the 5-HT1B receptor agonist RU-24969 (100 nM through the dialysis probe for 30 min) on 5-HT release was compared with rats chronically treated with saline. 8-OH-DPAT decreased 5-HT release to 55% and 60% of baseline, while RU 24969 decreased 5-HT release to 66% and 70% of baseline value in the saline and fluvoxamine group, respectively. In both cases, differences between the saline and fluvoxamine groups were not statistically significant. Plasma levels of fluvoxamine after 21 days of treatment ranged from 3 to 5 ng/ml. Fluvoxamine concentration in rat brain during treatment was estimated between 100 and 200 nM, which approximates to the IC50 value of fluvoxamine on the 5-HT transporter in synaptosomes and is 50 times higher than the Kd value for the 5-HT reuptake site. In conclusion, no evidence was found for changes in 5-HT1A,B receptor function using 8-OH-DPAT and RU-24969 as probes after continuous treatment with fluvoxamine by means of osmotic minipumps. PMID- 7770608 TI - The selective 5-HT3 receptor antagonist, WAY100289, enhances spatial memory in rats with ibotenate lesions of the forebrain cholinergic projection system. AB - The effects of three doses (0.003, 0.03 and 1.0 mg/kg sc) of the 5-HT3 receptor antagonist, WAY 100289, on spatial learning and memory in the water maze were examined in rats before and after ibotenate lesions to the nucleus basalis and medial septal brain regions at the source of cholinergic projections to cortex and hippocampus. The representative cholinergic nicotinic and muscarinic receptor agonists nicotine (0.1 mg/kg) and arecoline (1.0 mg/kg) were also tested for comparison. Both arecoline and nicotine improved initial acquisition in rats before lesioning, in terms of latency to find a hidden platform and accuracy of search strategy. WAY100289 did not affect the performance of normal rats significantly, apart from some non-significant trends towards improvement with the highest dose. However, in animals showing transient navigational deficits in retention and relearning after lesioning, WAY100289 improved performance at all three doses, though ameliorative effects of nicotine and arecoline were more marked also in lesioned rats. These results show that WAY100289 improved spatial learning in animals impaired after lesions to cholinergic projection nuclei, which may reflect an interaction with cholinergic transmission to enhance cognitive function. However, in the present study, WAY100289 appeared to be less effective than direct cholinergic agonists. PMID- 7770612 TI - Sedative potency and 2-[125I]iodomelatonin binding affinity of melatonin analogues. AB - Melatonin (5-methoxy N-acetyltryptamine), the hormone synthesized and released from the pineal gland each night, has sedative and sleep-promoting effects in experimental animals and man. In the present study, the sedative effect of melatonin and a number of analogues was determined by examining their ability to extend the duration of the loss of righting reflex ("sleeping time") in mice injected with pentobarbitone (50 mg/kg i.v.). All of the analogues tested produced a dose-related (5-20 mg/kg) potentiation of pentobarbitone sleeping time. In radioligand binding assays using 2-[125I]iodomelatonin in chicken brain membranes, all of the analogues were competitive inhibitors. There was no correlation between their ability to inhibit 2-[125I]iodomelatonin binding in chick and sedative potency in the mouse. Potentiation of pentobarbitone sleeping time by diazepam (1 mg/kg i.p.), but not melatonin (10 mg/kg i.p.), was blocked by pretreatment with the benzodiazepine antagonist, flumazenil (10 mg/kg i.p.). Similarly, an increase in pentobarbitone sleeping time produced by the aminoalkylindole cannabinoid receptor agonist, WIN 55212-2 (0.5 mg/kg i.p.), but not that produced by melatonin (10 mg/kg i.p.) was reduced by the cannabinoid receptor antagonist WIN 56098 (5 mg/kg i.p.). These studies confirm that melatonin has sedative activity and show that this action is shared by several structurally-related analogues but does not appear to be mediated by an interaction with benzodiazepine or cannabinoid receptors. PMID- 7770610 TI - Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. AB - An operant task for the measurement of sustained attention or vigilance in rats was characterized. The task requires the animals to respond to the presentation of visual signals (presented for 25, 50, or 500 ms) by operating one lever ("hits") and to the absence of a signal by operating the opposite lever ("correct rejection"). Incorrect responses ("misses" and "false alarms", respectively) were not rewarded. Performance in this task is a function of signal length, i.e., the shorter the signals the higher the number of misses. An increase in "background noise" by flashing the chamber houselight (at 0.5 Hz) impaired the animals' ability to discriminate between signal and non-signal events. Also flashing the houselight augmented the vigilance decrement observed for shortest signals. An increase in the event-rate also resulted in a vigilance decrement. Finally, the inability of the animals to time signals was examined by testing the effects of an increase in event asynchrony. In a second experiment, the performance of differently aged rats (6- and 20 month-old male BNNia/F344 rats) was studied. Compared to young animals, 20-month-old rats showed a decrease in their ability to discriminate between shortest signals (25 ms) and non-signal events but did not differ in their ability to correctly reject non-signal trials. Administration of the benzodiazepine receptor (BZR) agonist chlordiazepoxide (CDP; 3, 5, 8 mg/kg) resulted in an impairment of the animals' ability to discriminate between signal and non-signal events and, similar to the effects of age, this effect was exclusively due to an increase in the number of misses. CDP generally produced potent effects while affecting the aged animals to a greater degree. BZR-ligands with weak or "selective" inverse agonist properties (ZK 93426; beta-CCtB) did not affect vigilance performance. The BZR partial inverse agonist RU 33965 (0.1, 0.5 mg/kg) dose-dependently impaired vigilance performance. The administration of amphetamine (0.4, 0.8 mg/kg) also impaired performance, but these impairments were possibly based on effects unrelated to attentional mechanisms. The finding that performance in this task revealed the interactions between the effects of age and BZR agonists on attentional abilities further supports the validity of measures of performance generated by this task. PMID- 7770614 TI - Effects of lorazepam on human contrast sensitivity. AB - The anxiolytic lorazepam was studied for its effects on contrast sensitivity to gratings flickering in counterphase in normal volunteers. The drug significantly reduced contrast sensitivity at low spatial frequencies in a dose-related manner. The results are discussed with reference to possible GABA-mediated processes in the retina and lateral geniculate nucleus. PMID- 7770613 TI - Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study. AB - Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S Descloza) were measured in 30 chronic schizophrenic in- and out-patients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228-425) mg/24 h (range 100-700). There was a weak positive correlation between doses and the BPRS total score (r = 0.44, P < 0.05). The median S-Cloza was 1076 (706-1882) nmol/l (range 196-5581 corresponding to 64-1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r = 0.90; P < 0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r = 0.43; P < 0.05). The score values of the UKU Side Effect Scale were weakly (r = 0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects. PMID- 7770615 TI - Psychotherapeutic Medications Development Program (PMDP) Workshop on NMDA Receptor Antagonists: Neurotoxicity Evaluation. PMID- 7770616 TI - Psychotherapeutic Medications Development Program (PMDP) Workshop on NMDA Receptor Antagonists: neurotoxicity evaluation. Introduction. PMID- 7770617 TI - Neurotoxicity of NMDA receptor antagonists: an overview. AB - The glutamate transmitter system provides several benevolent/malevolent paradoxes. Glutamate itself serves vitally important functions in the CNS but has enormous neurodestructive potential. NMDA glutamate receptor antagonists protect many neurons against glutamate neurotoxicity, while injuring or destroying certain other neurons and inducing psychotic symptoms and memory impairment. Therefore, the challenge in developing protective therapies against glutamate's neurodestructive potential is to find benevolent agents that are not malevolent as well. There are two possible approaches. One is to develop neuroprotective agents that are free from neuropsychopathological side effects; the other is to use NMDA antagonists even though they have neuropsychopathological side effects, but to use them in combination with other agents that block the side effects without producing side effects of their own. PMID- 7770618 TI - Confocal microscopic visualization of MK-801-induced cytoplasmic vacuoles in vitro. AB - We examined neuroprotective and neurotoxic effects of the NMDA antagonist, MK 801, in primary cell cultures derived from embryonic mouse neocortex. Brief deprivation of oxygen and glucose, or direct application of N-methyl-D-aspartate (NMDA), resulted in acute neuronal swelling followed by neuronal death during the next day. This excitotoxic neuronal injury could be blocked by inclusion of a wide variety of NMDA antagonists in the cell culture medium. MK-801 attenuated neuronal death in the low micromolar range; 1 to 10 microM concentrations were sufficient to maximally reduce injury from NMDA toxicity, oxygen deprivation, or combined deprivation of oxygen and glucose. MK-801 alone caused no apparent toxicity at these concentrations in exposures of 24 to 48 hours. However, 24-hour exposure to 100 microM MK-801 resulted in appearance of cytoplasmic vacuoles, which could be visualized with immunofluorescence against the microtubule associated protein, MAP2, together with laser scanning confocal microscopy. Thus, at concentrations sufficient to block NMDA receptors, MK-801 is neuroprotective rather than neurotoxic for cortical neurons in vitro. This model system may provide a method to examine cellular mechanisms underlying the neurotoxicity of MK-801 at very high concentrations. PMID- 7770619 TI - Biochemical analysis of glial fibrillary acidic protein as a quantitative approach to neurotoxicity assessment: advantages, disadvantages and application to the assessment of NMDA receptor antagonist-induced neurotoxicity. AB - Hypertrophy appears to be a universal response of astrocytes, a central nervous system (CNS) cell type, to all forms of brain injury. The hallmark of this response, often termed "reactive gliosis," is the enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). Reactive gliosis traditionally has been examined qualitatively by immunohistochemistry of GFAP. But, the widespread availability of enzyme-linked immunosorbent assays (ELISAs) now makes it possible to quantify damage-induced expression of GFAP as a potential biomarker of diverse neurotoxic insults. To evaluate this possibility, we administered prototype neurotoxicants to experimental animals and then assessed the effects of these agents on the tissue content of GFAP, as determined by a recently developed sandwich ELISA. We found that assays of GFAP reveal dose-, time-, and region-dependent patterns of neural damage, often at toxicant dosages below those that cause light microscopic evidence of cell loss or damage. No false positives have been seen following exposure to a variety of pharmacological agents at therapeutic dosages. With respect to NMDA receptor antagonists, we find that MK-801 causes a large dose dependent increase in GFAP that, within the cortex, appears to be restricted to the retrosplenial zone. Among the advantages of the CFAP-based approach re its simplicity, objectivity, cost and the fact that the assay can be automated. Among the disadvantages are the need to perform brain dissections and the requirement for a time-course analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770620 TI - Neuronal injury produced by NMDA antagonists can be detected using heat shock proteins and can be blocked with antipsychotics. AB - Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, including ketamine, MK-801, and phencyclidine (PCP), induce the HSP70 heat shock or stress gene in pyramidal neurons in rat posterior cingulate and retrosplenial cortex. PCP also induces HSP70 in many other pyramidal neurons in brain including neocortex, insular cortex, piriform cortex, hippocampus, and basal nuclei of the amygdala. Several neurotransmitter antagonists, including haloperidol, clozapine, SCH-22390, diazepam, and muscimol, inhibited induction of HSP70 produced by PCP. Baclofen had no effect. Nifedipine blocked induction of HSP70 by PCP in cingulate, neocortex, and insular cortex but only partially blocked HSP70 in piriform cortex and amygdala. These data suggest that phencyclidine injures pyramidal neurons via dopamine D1, D2, D4, sigma, and other receptors. Gamma aminobutyric acid (GABA) agonists ameliorate the injury. A model is proposed whereby NMDA receptor blockade on GABA neurons decreases inhibitory inputs onto cortical pyramidal neurons and makes them more vulnerable to injury from a variety of excitatory inputs. It is possible that psychosis produced by PCP and other NMDA antagonists correlates with overactivity and eventual injury to cingulate pyramidal neurons. PMID- 7770621 TI - Effects of NMDA receptor antagonists on the developing brain. AB - This overview describes two effects of N-methyl-D-aspartate (NMDA) receptor antagonists that are not strictly speaking toxic: There are no signs that cells are dying. Nevertheless, these antagonists, if applied for prolonged periods in young children, could permanently cripple normal brain function. Disturbing the function of the NMDA channel during development can severely disrupt the wiring of defined neural circuits. It also can disrupt the developmental upregulation of the receptor protein itself and possibly many other molecular components of the synapse. PMID- 7770622 TI - Developmental aspects of NMDA receptor agonists and antagonists in the central nervous system. AB - Electrophysiologic responses to the glutamate agonist analogue N-methyl-D aspartate (NMDA) are enhanced in the developing nervous system compared to responses in the adult. Neurotoxicity mediated by comparable amounts of NMDA and its endogenous analogue quinolinate is more than 50 times greater in the 7-day old rat brain than in the adult. NMDA antagonist drugs reduce this neurotoxicity with the same spectrum of activity with which they prevent injury from hypoxic ischemic damage. The greater vulnerability of the immature brain to NMDA mediated injury is probably related to the enhanced role that NMDA mechanisms play in long term potentiation and activity-dependent plasticity during development. PMID- 7770624 TI - Assessing structural changes in the brain to evaluate neurotoxicological effects of NMDA receptor antagonists. AB - Like all pharmacologic agents known, N-methyl-D-aspartate (NMDA) antagonist compounds have side effects. It is expected that neuroactive molecules have effects, including side effects, in the central nervous system (CNS). With NMDA antagonists in rodents, these side effects are remarkably focal in the cingulate and retrosplenial cortex. The salient features of NMDA antagonist neurotoxicity which should be underscored are hypermetabolism, lactate accumulation, neuronal vacuolization in aldehyde fixed material, and neuronal death in older rodents. The scope of this phenomenon must urgently be determined in non-rodent species, specifically primates. This is important from both a regulatory and neurotherapeutic point of view, since effective molecules having potential in human disease states may also have NMDA antagonist properties. PMID- 7770623 TI - Pathological effects of MK-801 in the rat posterior cingulate/retrosplenial cortex. AB - Many N-methyl-D-aspartate (NMDA) antagonists cause vacuolization and necrosis in the posterior cingulate/retrosplenial (PC/RS) cortex of rats after single-dose administration. This article reviews a series of investigational studies that have characterized this effect. All the studies have used single doses of MK-801 in rats. Techniques employed were light microscopy, transmission electron microscopy, quantitative enzyme-linked immunosorbent assay (ELISA), and cell counting. Our studies demonstrated: (1) formation of vacuoles within 30 minutes of treatment, (2) dose-dependent necrosis of susceptible PC/RS neurons, (3) increased glial fibrillary acidic protein in response to neuronal necrosis, (4) significantly greater necrosis in female than in male rats, and (5) increases in necrosis along a rostrocaudal gradient within the PC/RS cortex. In addition, these studies illustrate a number of variables that impact the expression and detection of neuronal vacuolization and necrosis in rats after treatment with MK 801. PMID- 7770625 TI - Introduction to principles and procedures in behavioral testing. AB - This article serves as an introduction to the following two articles which describe the effects of drugs that interact with N-methyl-D-aspartate (NMDA) receptors on a number of behavioral baselines. The discussion in the subsequent articles focuses on detailed examination of performance on complex learning tasks, although effects of drugs affecting NMDA receptors on simple learned and unlearned behaviors are also mentioned. This article will provide a framework for interpretation of the results reported. To that end, a short primer on the principles of behavior is provided, followed by a description of a number of behavioral tests and discussion of issues important for the interpretation of results from such tests. The behavioral baselines discussed are, for the most part, the specific tasks from which data are presented in the following reports. A few additional descriptions have been included to illustrate specific points regarding data interpretation. The examples discussed are not necessarily representative of behavioral endpoints used routinely in the assessment of the behavioral effects of drugs. A number of reviews are available to the interested reader (Cabe & Eckerman 1982; Heise 1984; Rice 1990; Thompson & Shuster 1968; World Health Organization 1986). PMID- 7770626 TI - The impact of NMDA receptor antagonists on learning and memory functions. PMID- 7770628 TI - New Clinical Drug Evaluation Unit (NCDEU) meeting. Marco Island, Florida, 1994. Abstracts. PMID- 7770627 TI - Acute behavioral toxicity of MK-801 and phencyclidine: effects on rhesus monkey performance in an operant test battery. AB - Monkey performance of operant tasks was used to model several brain functions and monitor the acute effects of MK-801 and phencyclidine (PCP). MK-801 is a relatively selective N-methyl-D-aspartate (NMDA) receptor antagonist, while PCP is an NMDA antagonist that is also active at sigma opiate receptors. A comparison of these drugs' effects may indicate the relative importance of certain neurotransmitter receptor systems for specific behaviors. Learning and time perception behaviors are more sensitive (affected at lower doses) to the disruptive effects of MK-801 than are behaviors that model short-term memory, motivation, and color and position discrimination. Such selective disruption was not obtained for PCP: learning, short-term memory and attention, time perception, and motivation tasks are all equally sensitive to disruption. These findings suggest that specific brain functions are differentially affected by modulation of the NMDA and sigma opiate systems. PMID- 7770629 TI - Inhibition of acid secretory response and induction of ornithine decarboxylase and its mRNA by TGF alpha and EGF in isolated rat gastric glands. AB - TGF alpha shows structural and functional homology to EGF, but TGF alpha's mitogenic potency is greater. Our previous study showed that EGF may inhibit parietal cell secretory response through the induction of ornithine decarboxylase (ODC). The aim of this study was to determine parietal cell acid production in vitro in response to stimulation by TGF alpha and EGF and to compare the effect of these two growth factors on ODC activity and ODC mRNA in isolated rat gastric glands. 45 min treatment with TGF alpha and EGF had no effect on basal acid production but did inhibit histamine-stimulated acid production in a dose dependent manner. The two growth factors did not inhibit histamine-stimulated aminopyrine (AP) uptake from incubation medium with concentration of KCl increased from 5 to 70 mM. In the presence of specific ODC inhibitor, alpha difluoromethylornithine (DFMO), both EGF and TGF alpha failed to inhibit histamine-stimulated AP accumulation. Polyamine spermine also inhibited AP accumulation but this inhibitory effect was not affected by DFMO. After 1 h treatment with TGF alpha and EGF, ODC activities increased to an average 283 +/- 78% and 227 +/- 64% above the basal activity, respectively. 30 min treatment of gastric glands with TGF alpha and EGF resulted in, respectively, 2.9 +/- 0.4- and 2.7 +/- 0.5-fold increases of ODC mRNA level, as assessed by RT-PCR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770630 TI - Are enterochromaffinlike cell tumours reversible? An experimental study on gastric carcinoids induced in Mastomys by histamine2-receptor blockade. AB - A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine2-receptor blockade. In the present study the reversibility of ECL cell proliferation induced by acid inhibition was investigated. Short-term treatment (8 weeks) with the histamine2 receptor antagonist loxtidine caused a moderate hypergastrinemia, accompanied by a minor increase in histamine contents and a 2-fold increased volume density of the endocrine cells in gastric oxyntic mucosa. Eight weeks after withdrawal of treatment the volume density of endocrine cells was normalised as were the tissue levels of histamine, indicating a total reversibility of ECL cell hyperplasia. Long-term treatment (24 weeks) caused severe changes in the endocrine cell population of the oxyntic mucosa with neoplasia (5/21), dysplasia (11/21) and nodular hyperplasia (5/21). The endocrine cell density increased twofold and tissue histamine levels fourfold. 24 weeks after cessation of treatment, the endocrine cell density had decreased to 136% of controls, while histamine concentrations were normalised. The frequency of invasive carcinoids after recovery (4/23) differed only slightly from that seen after treatment for 24 weeks (5/21). Dysplastic lesions were only seen in 1/23 and hyperplastic lesions were of less severe type after recovery. The results demonstrate that ECL cell hyperplasia and dysplasia, induced by acid inhibition, are reversible after cessation of treatment. However, ECL cell tumours did not disappear, within the given observation period. One may therefore speculate that ECL cell proliferation is no longer reversible once the neoplastic (transformed) phenotype has developed. PMID- 7770631 TI - Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates growth hormone release from GH3 cells through type II PACAP receptor. AB - Effect of pituitary adenylate cyclase activating polypeptide (PACAP) on growth hormone (GH) release from GH3 cells was studied in a dynamic superfusion system. PACAP-38 and PACAP-27 stimulated GH release from superfused GH3 cells. The stimulatory effect of PACAP-38 was comparable to those of vasoactive intestinal polypeptide (VIP) and PACAP-27 at a concentration of 1 nM, but the duration of action was more prolonged in PACAP-38 than in the other two peptides. PACAP(6 38), a selective antagonist of PACAP, as well as a VIP antagonist blunted the GH release induced by PACAP-38 and VIP. An antagonist of GH-releasing factor (GRF) at a concentration of 1 microM, however, did not affect the GH release induced by PACAP-38. These findings suggest that PACAP and VIP stimulate GH release from GH3 cells through type II PACAP receptor but not through the GRF receptors. PMID- 7770632 TI - Potencies of various neurotensin-(8-13) analogs for inhibition of heat-induced edema in the anesthetized rat. AB - Peptides of the neurotensin (NT) and xenopsin (XP) families inhibit vascular leakage in various models of tissue injury. In this study, we measured the potency of NT fragments, NT analogs and NT-(8-13) analogs for inhibition of thermal edema induced by immersion of the anesthetized rat's paw in 58 degrees C water for 1 min. The pattern of anti-edema potencies seen with sixteen NT-(8-13) analogs correlated well with the pattern of activities obtained in binding measurements to rat brain membrane preparations and to activities in isolated organ preparations. Replacement of Tyr11 with Trp in NT-(8-13) and Arg8 with D Arg resulted in an analog [D-Arg8, Trp11]NT-(8-13) which was 5-times more potent than NT-(8-13). Substitution of D-Arg for Arg8 and Arg9 in NT-(8-13) produced analogs that retained anti-edema activity but with decreased effects on gut motility and hypotension. PMID- 7770633 TI - Role of extracellular and intracellular calcium on proctolin-induced contractions in an insect visceral muscle. AB - The pentapeptide proctolin requires extracellular calcium to produce an increase in frequency and amplitude of myogenic contractions and an increase in basal tonus of the oviducts of the locust, Locusta migratoria. Decreasing saline calcium concentrations reduced myogenic contractions, the delay to reach maximum basal tonus and the maximum basal tonus achieved. Proctolin (5.10(-9) M) resulted in an immediate influx of extracellular calcium into locust oviduct muscle during the first 15 s of stimulation. This was followed by an increase in calcium efflux which was maintained over the time of proctolin stimulation. A Na+/Ca2+ exchanger is suggested to occur in the oviducts and may play a role in Ca2+ extrusion following proctolin stimulation. PMID- 7770634 TI - G protein-coupled corticotropin-releasing hormone receptors in rat retina. AB - The presence of corticotropin-releasing hormone (CRH) receptors in rat retinal membranes was investigated by using [125I-Tyro]-ovine CRH ([125I]oCRH) as radioligand. The receptor binding was rapid, reversible, saturable and specific. The [125I]oCRH binding was completely displaced by different CRH-related peptides with a rank order of potency similar to that displayed in stimulating rat retinal adenylyl cyclase activity. Two populations of binding sites were detected: one with high affinity (Kd = 1.7 nM) and the other with low-affinity (Kd = 130 nM). The GTP analogue guanosine 5'-O-(3'-thiotriphosphate) reduced the high-affinity binding and increased the relative proportion of sites with low-affinity. Incubation of rat retinal membranes with the RM/1 antibody, which recognizes the carboxyl-terminus of the alpha subunit of the G protein Gs, prevented the CRH stimulation of adenylyl cyclase. In immunoblots, the RM/1 antibody recognized an immunoreactive protein band of 45 kDa and a protein with a similar electrophoretic mobility was ADP-ribosylated by cholera toxin. These data provide evidence for the presence of specific CRH receptors in rat retina and contribute to define the CRH signalling system in this tissue. PMID- 7770635 TI - Recombinant human chromogranin A: expression, purification and characterization of the N-terminal derived peptides. AB - Chromogranin A (CGA) is an ubiquitous 48 kDa secretory protein stored and released from most endocrine cells and is present in nanomolar concentration in the human vascular system. Recent data suggest that CGA may be the precursor of several peptides with a defined biological activity. The present report describes the expression of human CGA in Escherichia coli using the pET3a vector system, the purification and characterization of the recombinant protein and the production of antibody against the expressed protein. The expressed CGA was purified by a multi-step protocol including heat treatment, gel filtration and high performance-anion exchange chromatography and two-dimensional gel electrophoresis. Two major forms of recombinant human CGA (rhCGA) were purified from the bacterial cytosol: a 70 kDa form which corresponded to the native full length CGA and a major proteolytic 63 kDa product recognized by antibodies raised against the 70 kDa rhCGA or to synthetic peptides localized in the N-terminal part of the bovine CGA sequence. This E. coli expression system provides a method for producing a suitable protein which will permit the identification of CGA derived peptides with defined biological function in human. Fragments containing the N-terminal domain were generated by acidic cleavage of the two forms of rhCGA. A two-step purification using high-performance reverse-phase chromatography yielded 6 peptide bands ranging in apparent molecular mass from 7 to 18 kDa. Four components (molecular mass range 12-18 kDa) were immunostained with antibodies directed against synthetic sequences of bovine vasostatin II (bCGA1-113) while the two others (molecular mass range 7-8 kDa) were immunostained only with antibodies directed against vasostatin I (bCGA1-76). From protein staining the ratio vasostatins II/I was 10:1. The vasoinhibitory activity of this preparation was examined on isolated human saphenous vein segments. An inhibitory effect was obtained in paired vessel segments from 7 patients undergoing surgery for coronary artery bypass, however with low potency for supression of the endothelin-1 evoked sustained tension in these vessels. PMID- 7770636 TI - Mass spectrometric and biological characterization of guinea-pig corticotrophin. AB - Guinea-pig ACTH has been found to be distinct from other mammalian ACTHs in having an alanine for proline substitution at position 24 and in having superagonist aldosterone-stimulating activity relative to synthetic ACTH(1-24) in an isolated rat glomerulosa cell bioassay. We have purified ACTH from extracts of guinea-pig anterior pituitary and confirmed its unusual structural characteristics by amino acid analysis and mass spectrometry. Using isolated rat adrenal fasciculata-reticularis and glomerulosa cell bioassays, guinea pig ACTH was found to have similar activity to that of human ACTH with respect to corticosterone- and aldosterone-stimulating activity, in terms of maximal steroid output but was slightly more potent in terms of the concentration which elicited half-maximal steroid secretion. Under the assay conditions used, guinea-pig ACTH appeared not to be a superagonist as previously suggested. Various biosynthetic derivatives of guinea-pig pro-opiomelanocortin were identified by amino acid analysis and mass spectrometry. Joining peptide, a major product of pro opiomelanocortin processing, was found in extracts of both anterior and neurointermediate lobes of the pituitary. Post-translational modification of other products of intermediate lobe processing were observed. N- and O acetylation of alpha-melanotropin, partial O-phosphorylation of corticotropin like intermediate lobe peptide and carboxyl-terminal amidation of beta melanotropin were identified. PMID- 7770637 TI - Mesencephalic grafts increase preprotachykinin-A mRNA expression in striatal grafts in an in oculo co-graft model. AB - In oculo transplantation provides a powerful tool to study development and gene expression of isolated brain regions. In this study we grafted striatal and mesencephalic brain tissue to the anterior eye chamber and allowed it to survive for 2 and 6 weeks. Striatal or mesencephalic pieces were either grafted alone (single grafts) or together in close connection (co-grafts). As a control normal adult untreated rats were analyzed at the striatal and hippocampal level. Using non-radioactive in situ hybridization with digoxigenin-labeled riboprobes we detected preprotachykinin-A mRNA, a neuropeptide marker for striatal neurons. We report that adult normal rats show a strong expression of preprotachykinin-A mRNA in the striatum, medial habenula and piriform cortex, verifying the specificity of the method. Mesencephalic in oculo grafts did not reveal any staining for preprotachykinin-A mRNA. In single striatal grafts only a very weak expression of preprotachykinin-A mRNA was found at both time points investigated. Co-grafts grown for 2 weeks were not different from single striatal grafts, however, when striatum was grown together with ventral mesencephalon for 6 weeks the level of preprotachykinin-A mRNA was strong and near normal adult levels. We conclude that the mesencephalic dopaminergic innervation to the striatum might be a potent stimulus to neurons expressing preprotachykinin-A mRNA. PMID- 7770638 TI - Fundamental concepts and immunosuppressive treatment in the various forms of glomerulonephritis. AB - Immunosuppressive treatment in glomerulonephritis (GN) is still controversial. Most of the secondary forms of glomerulonephritis have the histologic features of one of the primary types of glomerulonephritis. Eight histologic expressions of primary glomerulonephritis can be distinguished and ordered in terms of severity of symptoms and prognosis: endocapillary GN, minimal change GN, mesangioproliferative GN, membranous GN, focal-sclerosing GN, membranoproliferative GN, focal-necrotizing GN, and rapidly progressive GN. Agreement exists only to the extent that immunosuppression is not required in endocapillary glomerulonephritis, although it is recommended in the other extreme of rapidly progressive GN. Primarily, an indication for immunosuppression is given by the severity of symptoms with a urinary protein excretion > 3.5 g per day and/or serum creatinine > 150 mumol per liter. As for anti-GBM, the type of glomerulonephritis is more important than the severity of symptoms in guiding therapy, whereas for IgA nephropathy it is controversial whether the prospective prognosis of even inexorably deteriorating renal function justifies immunosuppression. Renal biopsy is required to identify the type of glomerulonephritis so as to establish the specific immunosuppressive concept with different intensity and duration of treatment. Immunosuppression can reduce urinary protein excretion and improve deterioration of renal function; however, the proportion of patients responding varies with and depends on the different forms of GN. PMID- 7770639 TI - Effects of ursodeoxycholic acid on hemodynamic and renal function abnormalities induced by obstructive jaundice in rats. AB - The mechanism of renal function abnormalities in experimental biliary cirrhosis can be partially explained by the absence of gastrointestinal bile flow, which predisposes to translocation of intestinal endotoxin, a potent renal vasoconstrictor. Since bile acids prevent the absorption of intestinal endotoxins, we aimed to evaluate the effects of ursodeoxycholic acid (UDCA) administration on renal function and hemodynamic abnormalities induced by 1 week of obstructive jaundice in rats. METHODS: Fifty-two rats were used; 30 had ligation of the common bile duct, 22 were sham operated. Bile duct ligated rats were randomly and blindly assigned to receive UDCA (25 mg/kg/day, n = 14) or placebo (n = 16) during 1 week. Sham rats received no treatment. Portal pressure (PP) as well as creatinine clearance (CrCl), urinary sodium (US), and plasma renin activity (PRA) were evaluated. Results are mean +/- SEM, with a significant value of p < 0.05. RESULTS: Portal pressure (10.4 +/- 1.1 vs. 12.1 +/- 0.8 mm Hg) was significantly lower in UDCA than in placebo-treated rats. ALT serum levels were also significantly lower in bile duct ligated rats receiving UDCA (77.3 +/- 28 IU/L) than in placebo-treated rats (162 +/- 65 IU/L). US (1.1 +/- 0.5 vs. 2.1 +/- 0.3 mEq/24 h) was significantly lower and PRA (6.0 +/- 2.6 vs. 1.9 +/- 1.0 ng Ang 1/mL/h) higher in bile duct ligated than in sham-operated rats. No differences were found between UDCA or placebo-treated bile duct ligated rats. CrCl was similar between sham (0.39 +/- 0.12 mL/min/100 g BW) and UDCA (0.32 +/- 0.16) but significantly lower in placebo-treated (0.28 +/- 0.07) than sham operated rats (p < 0.05). CONCLUSION: UDCA administration had very mild effects on renal function abnormalities induced by experimental obstructive jaundice in rats. However, portal hypertension and biochemical abnormalities were partially improved. PMID- 7770640 TI - Renal cortical mitochondria are the source of oxygen free radicals enhanced by gentamicin. AB - Rat renal cortical mitochondria were isolated from Wistar male rats weighing 80 to 120 g to investigate whether the source of oxygen free radicals was renal cortical mitochondria enhanced by gentamicin. In renal cortical mitochondria with or without the addition of gentamicin, DMSO, DFO, CAT, SOD, and MT1 were added separately, then incubated at 37 degrees C for 90 min. Superoxide anions and hydroxyl radicals were then determined. The results showed that superoxide anions and hydroxyl radicals generated in mitochondria were enhanced by the addition of in vitro gentamicin (12.4 mg/mL) when compared to those without the addition of gentamicin. Dimethylsulfoxide (DMSO), catalase (CAT), and deferoxamine (DFO) significantly inhibited hydroxyl radicals enhanced by gentamicin, but superoxide dismutase (SOD) and metallothionein-1 (MT1) did not. SOD significantly inhibited the production of superoxide anions. Our data indicated that renal cortical mitochondria are the source of oxygen free radicals and that production is enhanced by gentamicin. This provides more insight on the pathogenetic role of hydroxyl radicals and superoxide anions in gentamicin-induced nephrotoxicity in vitro. PMID- 7770641 TI - A comparison of the effect of feeding a low-protein diet and of pharmacological intervention on the course of ablation nephropathy in the rat. AB - In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet; in one of the latter the lack of protein was substituted by saccharide, in the other by fat, making the substitution "isocaloric" in either case. In all three diet groups, subgroups were formed drinking either tap water or water containing either the ACE inhibitor enalapril (Ena) or the calcium antagonist diltiazem (Dil), or both (Ena + Dil). In the high protein diet group, increases in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) were seen. This was prevented by feeding either type of the low-protein diet but also by Ena and Ena + Dil. Ena and Ena + Dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of Ena + Dil or Ena + low protein or Ena + Dil + low protein was seen, suggesting that a bottom limit of these protective action was reached by the low-protein diet alone. There was no substantial difference between either type of the low-protein diet except a small and transient decrease in body weight in the first week of fat-rich diet administration. PMID- 7770642 TI - Age-related ANP release in response to acute vs. chronic sodium loading. AB - Atrial natriuretic peptide (ANP) levels were studied in young (2-week-old) and old (age 20 months) rats following acute (20 mL/kg bolus of normal saline i.v.) vs. chronic sodium loading (high-salt diet for 21 days). In both groups serum ANP rose significantly 1 h post i.v. loading. However, the increment was greater in the old animals. On chronic sodium load, in the young group, ANP rose significantly on days 3 and 7, subsequently declining to baseline. In the old animals, no increase in ANP was noted throughout the chronic experiment. Twenty four-hour urinary sodium excretion was similar in the two groups following acute or chronic salt load. The results suggest that: (1) The old kidney requires a greater ANP stimulus to excrete a given acute i.v. sodium load. (2) The relatively diminished elasticity of the old heart plays a major role in the exaggerated ANP release in response to a bolus i.v. load of saline. (3) The role of ANP in maintaining homeostatic renal sodium excretion during short-term sodium oral loading is different in the two age groups. PMID- 7770643 TI - Tubular damage in microalbuminuric patients with primary glomerulonephritis and diabetic nephropathy. AB - Tubular damage as suggested by enzymuria and tubular proteinuria is a recognized feature of glomerulonephritis (GN) with clinical proteinuria and both incipient and overt diabetic nephropathy (DN). However, little is known about the presence of tubulopathy in patients with primary GN, microalbuminuria [albumin excretion (AER) 30-300 mg/d] and microhematuria. Three groups were studied. The GN group comprised 17 (2 F) patients with biopsy-proven GN with microalbuminuria. The DN group comprised 35 (14 F) patients with incipient diabetic nephropathy with AER 30-300 mg/d, and controls comprised 38 (15 F) normal subjects with normal AER < 30 mg/d. Serum creatinine, albuminurinuria, transferrinuria, and markers of tubular damage such as urinary excretion of N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), gamma-glutamyl transferase (gGT), and retinol binding protein (RBP) were measured. GN and DN had comparable degrees of albuminuria, transferrinuria, and LAP excretion, and these were significantly higher than controls. Serum creatinine was significantly higher in GN than DN and controls. DN had significantly higher NAG and RBP, and lower gGT than GN and controls. In both GN and DN groups, both glomerular proteins correlated with each other and NAG correlated significantly to LAP and gGT. Albuminuria correlated to tubular enzymuria in GN group but not in patients with DN. The results suggest that tubular damage is less marked in microalbuminuric patients with GN than those with DN despite similar degree of glomerular proteinuria. The pattern of tubulopathy is also different in the two groups, indicating differences in the pathogenesis of tubular damage in these two clinical settings. PMID- 7770644 TI - Daily peritoneal dialysis using a surgically placed Tenckhoff catheter for acute renal failure in children. AB - Thirty-one infants and children with acute failure were treated with peritoneal dialysis using a surgically placed Tenckhoff catheter. In 10 patients a peritoneal dialysis cycler was used, and 21 were dialyzed by the manual method. Initially, hourly exchanges were given for 24 to 48 h and, as the patients stabilized, 10 exchanges per day at 1-h intervals were given. The mean stabilization period was 36 +/- 8 h. The predialysis mean serum creatinine was 5.8 +/- 1.8 mg% and the serum creatinine while on daily dialysis was 2.8 +/- 1.1 mg%. Peritoneal dialysis succeeded in controlling metabolic abnormalities and improving fluid balance. All the catheters except one functioned immediately following insertion. Median duration of catheter placement for dialysis was 18 days (range 2 to 90). The incidence of peritonitis was 12.8%, and exit site infection was 6.4%. The infection rate was decreased when a cycler was used compared with the manual method (23.8% vs. 10.0%), though not statistically significant. Two patients developed hypothermia while being dialyzed via the manual method. To conclude, 10 daily peritoneal dialysis exchanges performed at 1 h intervals after initial stabilization using a surgically placed Tenckhoff catheter is an effective and safe mode of dialytic therapy for children with acute renal failure. Complications (infection and hypothermia) are reduced with the use of a cycler. PMID- 7770645 TI - Decreased urinary excretion of beta-glucuronidase in sickle cell anemia in Nigeria. AB - The activities of five lysosomal hydrolases--namely beta-glucuronidase, beta hexosaminidase, beta-galactosidase, alpha-galactosidase, and alpha-mannosidase- were measured in the plasma and urine of children (ages, 7 to 15 years) with sickle cell anemia (n = 11) and controls (n = 11) from Jos, Nigeria. The presence of SS hemoglobin was confirmed by electrophoresis of red cell hemolysates. Albuminuria was absent in all of the patients with sickle cell anemia. The creatinine-indexed urinary activity level (units of enzyme activity/milligrams creatinine) and the fractional enzyme excretion (FEE) value, which is defined as the ratio of enzyme clearance to creatinine clearance, were determined for each of the five lysosomal enzymes and compared between the two groups. The mean FEE values for beta-glucuronidase and alpha-galactosidase in the sickle cell patients were 10- and 3.5-fold lower, respectively, than the corresponding control values, and these differences were statistically significant (p < .03) for both enzymes; however, beta-hexosaminidase, beta-galactosidase, and alpha-mannosidase levels in urine were not different between the two groups. When indexed to creatinine, a comparison of the urinary enzyme levels of control and sickle cell patients showed significant differences for beta-glucuronidase (p < .01) and alpha galactosidase (p < .05) but not for the other three enzymes. Differences in level of plasma enzyme activity between control and sickle cell patients were not significant, except for alpha-galactosidase (p < .05), which was increased slightly (25%) in the sickle cell group. These data indicate that there may be abnormalities in the metabolism of lysosomal enzymes in the kidneys of patients with sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770646 TI - Interpretation of positive edrophonium (Tensilon) test in patients with end-stage renal disease. AB - Many patients with end-stage renal disease (ESRD) have signs and symptoms of easy fatigability, fluctuating weakness, apathy, dry mouth, and blurring of vision. These symptoms can be confused with disorders of neuromuscular transmission. When present, the physician may want to determine whether the patient has myasthenia gravis--the commonest of all neuromuscular disorders--and administer the edrophonium (Tensilon) test. An unequivocally positive response to the test must be interpreted with caution in ESRD. However, the exact mechanism of a positive response is unclear but may be explained by metabolic abnormalities related to end-stage renal disease, i.e., uremic toxins, disordered calcium metabolism, abnormal neuromuscular mechanism, associated neurological disorders, or myopathic processes in uremia, all of which can affect neuromuscular transmission. PMID- 7770647 TI - Safe employment of recombinant human erythropoietin in pregnancy in two anuric patients on regular dialysis treatment. PMID- 7770648 TI - Was Beethoven's cirrhosis due to hemochromatosis? AB - Dr. Wagner's description of an advanced macronodular cirrhosis is compatible with end-stage liver disease due to a variety of causes. An alcoholic etiology seems more probable than chronic viral hepatitis since such a diagnosis might also account for the chronic pancreatitis, unless it was related to the cholelithiasis. However, Dr. Wagner's description favors a diagnosis of biliary pigment sludge related to hemolysis. Furthermore, the controversy over the extent of Beethoven's alcohol consumption and the absence of mention of pancreatic calcification weakens the case for an alcoholic etiology. On the other hand, Dr. Wagner's emphasis of bluish-green pigmentation of the liver, blackish pigmentation of the spleen, and an arteropathy of the hepatic vessels suggests the probability of hemochromatosis, which diagnosis is also in keeping with Beethoven's medical history. In this regard the composer's history of recurrent obscure abdominal pain, commencing in his third decade, is especially in keeping with hemochromatosis. As many as a third of patients present with recurrent abdominal pain, and eventually up to 40% of cases develop significant abdominal pain in the course of their disease. While some of these cases of abdominal pain have been attributed to hepatoma, ascites, pancreatitis, perisplenitis, or diabetic neuropathy, the majority remain ill-defined (32). Even so, the diagnosis of hemochromatosis remains unproved in the absence of a histological examination and measurement of hepatic iron concentration. It is proposed that the combined additive, toxic effects of alcohol and iron were the most likely cause of Beethoven's cirrhosis. PMID- 7770649 TI - [Post-therapeutic follow-up of oral spinocellular epithelioma]. AB - During the follow-up of patients treated for squamous cell carcinoma, dentists have to look for recurrences and metastases. They play also a very important role in the prevention and treatment of the different treatment induced oral sequelae. Special attention is drawn to the postradiation complications like mucositis, xerostomia, radiation caries, trismus and osteoradionecrosis. Despite the fact that no universal accepted protocols are available, the author presents some therapeutic procedures, based on the review of the literature and clinical experience. The importance of a long time follow-up is underlined. PMID- 7770650 TI - [Oral cancer. Precancerous conditions]. AB - In the precancerous lesions leukoplakia is the most frequent. This is only a clinical diagnose and a biopsy is necessary to see if there is a malignant transformation. A mycosis in a leukoplakia may be an important indicator for a local or system impairment of the immune system. PMID- 7770651 TI - [Oral cancer. The importance of early diagnosis and role of the dentist]. AB - Early diagnosis is an significantly relevant factor in the prognosis of oral cavity carcinomas. Knowledge of the clinical and oral manifestations of pre cancerous lesions in general dentistry is of paramount importance. The initial treatment, follow-up schedule and reference timing are given in a decision chart. Special attention is given to the timing of biopsies in the treatment plan. PMID- 7770652 TI - [Spinocellular epithelioma of the oral mucosa. Description, development, localization]. AB - The presentation of the oral squamous carcinoma is described. The oral cavity has been divided into five sites: the tongue, the floor of the mouth, the gingiva, the cheek and the palate. For each location the presentation and the evolution of the squamous carcinoma is described. PMID- 7770653 TI - [Assessment of extension and staging of oral cancers]. AB - Cancers of the oral cavity are most frequent during the 6th to 8th decades and tobacco and alcohol are major risk factors. Diagnosis must be made by bimanual palpation and biopsy. Local invasion is best evaluated by CT-scanner and Magnetic Resonance Imaging for the primary tumor and by ultrasonography for neck nodes. For therapeutic and prognostic goals, staging of the tumor must be estimated before first treatment according to the AJCC and the UICC classification. PMID- 7770655 TI - [Prosthetic rehabilitation following surgical removal of a maxillary or mandibular tumor]. AB - Modern oral cancer therapeutic techniques unfortunately remain too often impairing. On the other hand, rebuilding techniques fortunately allow the patient as well as the practitioner to expect with increasing optimism the restoration of a satisfying function. Those techniques resort, among others, to grafting by bone pedicled transplants and endosseous osseointegratable implants. Irradiated tissues, however, require the utmost care. PMID- 7770654 TI - [Treatment of oral epidermoid carcinoma]. AB - This review analyses systematically all therapeutical known features about oral cancer. Every therapeutic modality involving surgery, radiotherapy and chemotherapy is detailed and an exhaustive literature review about each therapy concept is made. PMID- 7770656 TI - [Oral cancer: epidemiology and prognosis]. AB - More than 90% of intra-oral malignancies are squamous cell carcinomas. Oral cancer is far more frequent in developing countries than in developed ones. This has probably to do with the differences in the use of tobacco and alcohol and with factors such as oral hygiene, nutrition and general resistance. Through an increased interest for epidemiological studies certain factors are suspected as carcinogenic. They can grossly be divided into chemical, physical and biological. Even though it is often hard to prove the real relation of cause to effect, one can no longer deny the detrimental role of tobacco, of many alcoholic drinks, of poor oral hygiene, of nutritional deficiencies, of short wave irradiation, and possibly of certain viruses. These factors must further be investigated because the overall prognosis of oral cancer is not very good. Determinant in survival are the volume of tumor present (surface and depth), its growth pattern, its localisation, eventual lymph node involvement and general hematogenic metastases, ... The overall five-year survival seems to range between 10% for T4N3 and 95% for T1N0 cases. Early detection and efficient prevention must therefore be encouraged. PMID- 7770657 TI - [Dental prosthesis rehabilitation following oral carcinologic treatment]. AB - Following the different treatments applied on patients suffering of a mouth cancer, often these are confronted with a functional and esthetic handicap. Thanks to the prosthetic techniques and an eventual resort to implantation, it is possible to improve their quality of life. Different prosthetic reconstructions are considered. PMID- 7770658 TI - [Experimental vaccination of SPF chickens against Newcastle disease using the method of coated-millet vaccine from a thermotolerant variant of the LaSota virus]. AB - The thermotolerant variant A300 of LaSota virus was used to vaccinate 4 week old specified pathogen-free (SPF) chickens by feeding them with virus coated-millet. With vaccine doses above 10(6)EID50/bird, HI antibodies developed and protection to challenge was seen 2 months after vaccination, while 100% mortality occurred in the control groups. The PD50 was estimated to 10(6.85) EID50. This lyophilized vaccine intended for African village chickens can be kept at ambient temperature for at last 1 week up to 35 degrees C. Other trials on a large scale are still needed to determine the potential of this vaccine in the field conditions of rural Africa. PMID- 7770659 TI - First report on the isolation of Brucella abortus biovar 3 from camel (Camelus dromedarius) in the Sudan. AB - Three isolates of Brucella abortus biovar 3 were recovered out of 38 different samples obtained from free-ranging camels (Camelus dromedarius) in Eastern Sudan. The biochemical characters of the isolates were identical to those of the other types of B. abortus except that they were oxidase negative. PMID- 7770660 TI - [Epidemiology of digestive parasitic diseases of young cattle in northern Cameroon]. AB - Studies of gastro-intestinal parasites of zebu calves were carried out in traditional herds in Northern Cameroon through monthly faecal analysis in 17 herds for a period of two years. Toxocarosis appeared to be the most important parasitic infection in the North province where its prevalence reached 58% in calves aged 0-6 months; 60% of the infested calves passed large numbers of eggs at least once. Samples revealing high egg counts were more frequent in the dry season. Deworming calves aged one month with a cheap anthelmintic against Toxocara is likely to be economically profitable in the North. Seventy-five and a half per cent of the calves 0-12 months old were infested with Strongyloides; high counts of Strongyloides eggs were registered at least once for 31% of these calves. As for toxocarosis, calves seemed to be more often and more heavily infested with Strongyloides in the North than in the Far North province. Strongyloidosis was apparently of low clinical importance, with the rare clinical manifestations accompanied by toxocarosis. The importance of digestive tract strongylosis was difficult to evaluate. Every steer was affected at one stage of its life in a similar manner in the two provinces; 6.8% of samples showed high egg counts and 35% of the steers aged over six months passed large numbers of eggs at least once. These results did not permit a priori recommendation of a systematic deworming programme against strongyles; instead, several less intensive deworming programmes have to be tested in order to determine their economic profitability. Coccidia were found in 77.4% of calves aged 0-12 months, with heavier and more frequent infections in the North. However, infections of high intensity were generally rare. Trichuris, Moniezia, Fasciola and paramphistomes were rarely found. Concerning nematodosis, curative treatments and cost-profit studies of deworming programmes should be aimed at toxocarosis in calves aged 0-3 months in the North, and strongylosis in steers aged 6-12 months, in both provinces. PMID- 7770661 TI - Efficacy of chlortetracycline for controlling goat coccidiosis in Burundi. AB - Eighteen cross-bred goats of Burundi naturally infected to varying degrees with multiple coccidia species of the genus Eimeria were orally administered 25 mg/kg body weight/day chlortetracycline. Effectiveness percentages more elevated than 99.0% were reached within the 9th day of treatment. No adverse reactions have ever been reported. Results demonstrate that the antibiotic is effective for the control of coccidiosis of goats naturally infected in Burundi. PMID- 7770662 TI - Pig trypanosomosis: prevalence and significance in the endemic Middle Belt zone of southern Nigeria. AB - Abattoir and field/market surveys of 1,954 crossbred pigs aged 6 to 30 months, for trypanosomosis in the Middle Belt zone of Southern Nigeria, revealed a 26.8 infection rate. Of those infected, 66.5, 23.9 and 8.2 % were due to mixed, single Trypanosoma brucei and T. congolense infections respectively. Although 1.5 % of the infections were unidentified, there was no evidence of T simiae. The infection rate was significantly higher (p < 0.05) among the abattoir pigs (37.8 %) than among the farm pigs (21.8 %) in both sexes. Peak infection was noted among pigs aged 11 to 15 months and during the end of the rainy season and the beginning of the dry season (September to December). Complementary mice inoculation tests revealed 83 subpatent and prepatent cases and are being recommended as a confirmatory diagnostic technique. The disease poses problems for pig productivity and the cooperation of scientists is essential. PMID- 7770663 TI - Efficacy of Cymelarsan in the treatment of natural chronic Trypanosoma evansi infection in camels in the Sudan. AB - The efficacy of Cymelarsan, administered by intramuscular (i/m) injection in the treatment of chronic cases of camel trypanosomosis due to Trypanosoma evansi, was tested under controlled laboratory conditions. It was confirmed that Cymelarsan is a safe drug for use in dromedary camels when administered i/m at dose rates of 0.25 or 0.50 mg/kg body weight. During the 90 days post-treatment no relapses occurred at either dose rate. Hence, the drug was found to be fully effective against the chronic form of the natural disease. A dose of 0.25 mg/kg body weight of Cymelarsan given i/m is recommended. PMID- 7770664 TI - [Field trial of an attenuated vaccine against heartwater disease]. AB - The results are given of a field trial using a Senegalese stock of Cowdria ruminantium which had been attenuated by passage in cell culture. Thirty vaccinated and thirty control sheep were exposed in the Niayes region of Senegal and were monitored daily. In the control group, 22 animals died of heartwater, associated in one case with anaplasmosis. In the vaccinated group, 13 animals died; Cowdria was found only in two sheep which had previously suffered from ehrlichiosis or anaplasmosis; three other cases of ehrlichiosis and two of anaplasmosis were also observed among these 13 animals. The resistance of the two vaccinated animals which showed Cowdria in their cerebral cortex was apparently lowered by the intercurrent infections. The other animals of the vaccinated group showed no evidence of Cowdria infection. PMID- 7770665 TI - Effects of potassium and lactic acid on chemoreceptor discharge in anaesthetized cats. AB - Both increasing [K+]a and falling pHa stimulate ventilation through an action on the peripheral chemoreceptors. We have examined the effect on afferent carotid chemoreceptor discharge, of intravenous infusion of lactic acid alone, KCl alone, and both combined at constant PETCO2 in anaesthetized, artificially ventilated cats. Infusions of lactic acid alone and KCl alone caused similar increases in both the mean and amplitude of oscillation of chemoreceptor discharge. In the case of the lactic acid alone infusion the increase in the amplitude of oscillation could be accounted for by the resultant increase in carbon dioxide production. Simultaneous infusion of KCl and lactic acid caused an increase in the mean and amplitude of the discharge which was greater than either given alone, although the combined effect was less than additive. The alterations in mean and amplitude of oscillation of discharge during infusion of both agents together may be completely accounted for by a combined effect of increased carbon dioxide production and elevated [K+]a. PMID- 7770666 TI - Scaling of hypercapnic ventilatory responsiveness in birds and mammals. AB - The possible relationship between CO2 responsiveness and body mass in birds was explored using newly acquired ventilatory data from the barn swallow, Hirundo rustica, and the pigeon, Columbia livia, and that from the literature on four other species. Ventilatory responsiveness (% delta V) of birds to 5% inspired CO2 is scaled to body mass to the 0.145 power (% delta V alpha Mb 0.145). A similar allometric relationship exists for data on 7 species of eutherian mammals taken from the literature (% delta V alpha Mb0.130). The The reduced responsiveness to CO2 in small birds and mammals may be related to an elevated hypoxic ventilatory sensitivity, as demonstrated in mammals (Boggs and Tenney, Respir. Physiol. 58: 245-251, 1984). These scaling relationships may reflect a mechanism for minimizing the inhibition of ventilation resulting from excessive loss of CO2 which thereby permits a higher hypoxic ventilatory response in small species. Other mechanisms, however, could include size related differences in mechanics or alveolar ventilation. PMID- 7770667 TI - Diaphragm and phrenic nerve activities during inspiratory loading in anesthetized rabbits. AB - To determine whether decreases in neural activation and/or neuromuscular transmission to the diaphragm contribute to ventilatory failure observed during inspiratory resistive loaded breathing, peak integrated activity of the intact phrenic nerve (ENGdi) and costal diaphragm (EMGdi), transdiaphragmatic pressure swings (Pdi) and evoked diaphragm compound action potentials (M-wave) were measured in anesthetized rabbits subjected to inspiratory resistive loads of varying intensities and duration breathing supplemental oxygen. Sustainable loads were studied for 4 h. Severe loads were applied in increments and studied for 50 min each. Loading resulted in parallel increases in ENGdi, EMGdi and Pdi that stabilized within 20 min. With severe loading, peak inspiratory pressure (Pao = 55 +/- 4 cm H2O) was maintained for 30 min after which there was a significant drop in inspiratory pressure (task failure). Despite hypoventilation and profound changes in blood gases, both activation (ENGdi) and neuromuscular transmission (ENGdi/EMGdi ratio or M-wave) were maintained throughout all loads even at task failure when a critical level of PaO2 (27 +/- 1 mm Hg) was reached. We conclude that neural activation and neuromuscular transmission to the diaphragm do not fail during inspiratory resistive breathing and discuss our findings in terms of current concepts of diaphragm fatigue and control of breathing in this model. PMID- 7770668 TI - Changes in pharyngeal respiratory muscle force produced by K+ channel blockade. AB - The purpose of the present study was to determine whether the contractility of pharyngeal respiratory muscles can be augmented by altering membranous K+ channel conductance. The effects on twitch force of two K+ channel blockers, tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 0.3 mM), were examined in vitro for sternohyoid and diaphragm muscle strips. Both agents augmented isometric twitch force of both muscles. In response to TEA twitch force of the sternohyoid muscle increased significantly more than that of the diaphragm (by 33 +/- 7 vs. 9 +/- 1%, P = 0.004), whereas with 4-AP the increase in twitch force of the sternohyoid muscle was comparable to that of the diaphragm (55 +/- 15 vs. 64 +/- 6%, P = 0.50). 4-AP shifted the force-frequency relationship of both muscles leftward but did not alter peak tetanic force, so that force with 4-AP exceeded that without drug at stimulation frequencies below 60 Hz. In contrast TEA reduced force at stimulation frequencies > 20 Hz. The isometric contraction times of both muscles was variably prolonged, more so with 4-AP (by 30 +/- 15% for the sternohyoid and 32 +/- 3% for the diaphragm) than with TEA (by 9 +/- 2% for the sternohyoid and 5 +/- 2% for the diaphragm). For the group of muscles and K+ channel blockers, the degree of augmentation of twitch force correlated with the degree of prolongation of contraction time (r = 0.82, P < 0.001), consistent with blocking delayed rectifier K+ channels as the mechanism of increasing muscle force. PMID- 7770669 TI - A finite element analysis of the effects of the abdomen on regional lung expansion. AB - A finite element model of the dog lung, heart and abdomen, consisting of three solid linearly elastic bodies, was developed to study the effects of gravity on the vertical stress distribution and lung volume in different body positions at functional residual capacity (FRC). The geometry of the lung was obtained from an isolated dried dog lung after inflation to total lung capacity (TLC). The compliance of the rib cage, diaphragm and the abdomen was simulated by spring elements located on their surfaces. In the prone position, gravitational forces acting only on the lung contributed to the vertical gradient (0.19 cmH2O/cm) in transpulmonary pressure (Ptp). This result was independent of chest wall compliance. In the supine position, the addition of the heart and abdomen with a compliant diaphragm and abdominal walls increased the vertical Ptp gradient to 0.53 cmH2O/cm. In the head-up (upright) position, both heart and abdominal weight contributed to the vertical gradient (0.47 cmH2O/cm). Diaphragmatic compliance was of less importance to the vertical gradient in the head-up and head-down positions in the absence of the abdomen. The smallest vertical gradient (0.11 cmH2O/cm) was obtained in the head-down position with abdominal weight reducing the gradient caused by lung weight. Lung volume at FRC was virtually unaffected by gravity in the prone body position, was reduced by gravity in the supine and head-down positions but increased in the head-up position. The effects of a compliant diaphragm and abdominal weight are important contributors to the distribution of stress and volume in the intact lung. PMID- 7770670 TI - Increased insensible water loss in feline retrovirus-infected cats. AB - Feline retroviruses such as feline leukemia virus (FeLV) adversely affect the regulation of many vital host systems such as the immune response, erythropoiesis, and nutrient metabolism. In this paper, we describe the disruption of an additional homeostatic mechanism-evaporative water loss-by FeLV. Viremic cats had greater evaporative water losses (24.0 +/- 1.4 gm water/kg per day) at low relative humidity levels (19% to 25% relative humidity) when compared to age- and sex-matched control cats (19.7 +/- 1.4 gm of water/kg per day [P < 0.05]). At relative humidity levels greater than 50%, viremic and control cats had similar evaporative water losses. Viremia also resulted in an elevation in the average body temperature (39.1 +/- 0.5 degrees C) compared to control cats (38.4 +/- 0.3 degrees C) (P < 0.001). However, the energy expenditure of viremic cats (17.14 +/- 1.60 kJ/kg/h) was not significantly different from the energy expenditure of control cats (17.02 +/- 2.22 kJ/kg/h). The elevated body temperature of viremic cats likely causes a greater increase in evaporative water loss at low relative humidity levels and suggests further study of water balance in retroviral infection is warranted. PMID- 7770671 TI - Malignant lesions of the female genital tract and peritoneum that may be underdiagnosed. AB - Female genital tract neoplasms that may have a deceptively benign appearance and selected frankly malignant neoplasms that may be misinterpreted as less aggressive lesions are reviewed. In the uterine cervix, the two major neoplasms in this group are the minimal deviation adenocarcinomas of mucinous and endometrioid types. The latter subtype has only recently been described. Endometrioid adenocarcinomas, usually of the uterine corpus, but occasionally of other sites, may have microglandular patterns that can lead to their misdiagnosis, sometimes as microglandular hyperplasia. Pure squamous cell carcinomas of the uterine corpus frequently are composed of very well differentiated epithelium, so that it is possible to misinterpret them as nonneoplastic, and a similar phenomenon may occur in association with the squamous element in some adenocarcinomas with squamous differentiation. Other uterine entities that may be underdiagnosed are malignant lymphoma of the cervix, placental site trophoblastic tumor, myxoid leiomyosarcoma, endometrial stromal sarcoma with glandular differentiation, and mullerian adenosarcoma. Consideration of a variety of architectural and cytological features should facilitate their interpretation. One recently described variant of adenocarcinoma of the fallopian tube that may be confused with the usually clinically benign female adnexal tumors of probable Wolffian origin is microfollicular endometrioid adenocarcinoma. Ovarian tumors subject to misinterpretation that are reviewed herein include metastatic tumors with deceptively benign foci, endometrioid adenocarcinomas that may be misdiagnosed as sex cord tumors, and cystic granulosa cell tumors that may be misinterpreted as follicle cysts. Finally, rare variants of malignant mesothelioma that may be underdiagnosed are reviewed. PMID- 7770672 TI - Malignant breast lesions that may mimic benign tumors. AB - It has been estimated that approximately 1 in 9 women (living to age 85 years) in the United States will develop breast cancer at some time in their lives; hence the interpretation of breast biopsies has become a large and important component of the surgical pathologist's practice. Indeed, there is great pressure on surgical pathologists to make accurate diagnoses of breast lesions because of their high incidence, the increased public awareness of breast disease, the greater use of screening mammography to detect early carcinomas, the development of multiple therapeutic options (which is often determined by tumor pathology), and the harsh medical-legal climate. The focus of this article will be to define the clinicopathologic features of two malignant breast lesions that are particularly prone to simulate benign lesions, and thus pose important diagnostic problems to surgical pathologists. The two lesions include spindle-cell carcinoma and low-grade duct carcinoma in situ. PMID- 7770673 TI - Malignancies in the lung and pleura mimicking benign processes. AB - As pathologists, we are most concerned about overcalling reactive changes in the lung as carcinoma and the fact that malignant processes may be misinterpreted as benign processes in the lung is less well recognized. This review covers five such lesions. Well-differentiated adenocarcinomas, especially bronchioloalveolar carcinomas, are frequently undercalled, particularly in small biopsy and cytology specimens. In such cases, one must pay particular attention to the uniformity and monotony of the epithelium even though it may be extremely well differentiated. Spindle cell carcinomas may have necrosis and cavitation, interstitial growth, and a reactive fibroblastic reaction, and thus be mistaken as organizing inflammatory processes. Careful attention to the atypical cytological features, prominent vascular invasion, and getting immunohistochemical supports helps in recognizing them. Lymphoid lesions of the lung present a number of problems; small lymphocytic lymphomas and Hodgkin's disease are often misinterpreted as inflammatory processes. Intravascular lymphomatosis in the lung may be misinterpreted as an interstitial pneumonia if one does not appreciate the atypical lymphoid cells within the capillaries. The desmoplastic variant of sarcomatous mesothelioma may be extremely difficult to diagnose, because large portions of the tumors are composed of bland-appearing fibrous tissue. A case of desmoplastic mesothelioma presenting predominantly as a mediastinal mass is discussed, and problems in differential diagnosis are outlined. Angiosarcomas are rare tumors, but an appreciable percentage of them present as pulmonary metastases which may be interpreted as pulmonary hemorrhage or organizing infarction. The clinical and radiographic pattern, usually mimicking metastatic disease, and the fact that atypical spindle cells occlude small pulmonary arteries with surrounding alveolar hemorrhage are clues to the recognition of these lesions. PMID- 7770674 TI - Endocrine malignancies that may mimic benign lesions. AB - A variety of malignant tumors that occur in endocrine organs may mimic benign lesions histologically. In this article, a number of such tumors are selected for discussion, including several variants of papillary thyroid carcinoma (encapsulated follicular, diffuse sclerosing, diffuse follicular, macrofollicular, cystic, and stroma-rich), paucicellular anaplastic thyroid carcinoma, primary thyroid low grade B-cell lymphoma of mucosa-associated lymphoid tissue type, adrenocortical carcinoma, and parathyroid carcinoma. Emphasis is placed on the histological clues that are helpful for recognizing the malignant nature of these lesions. PMID- 7770675 TI - Malignant liver tumors that mimic benign lesions: analysis of five distinct lesions. AB - The diagnosis of malignant liver tumors has long been an important part of surgical pathology, but now with improved radiographic and biopsy techniques, the appropriate pathological identification and differentiation of malignant from benign liver lesions has become even more critical. This review discusses five examples of malignant lesions that may be underdiagnosed as benign: well differentiated hepatocellular carcinoma, fetal and macrotrabecular hepatoblastoma, well-differentiated cholangiocarcinoma, Kaposi's sarcoma, and epithelioid hemangioendothelioma. PMID- 7770676 TI - Malignant lymphomas that mimic benign lymphoid lesions: a review of four lymphomas. AB - Lymphomas that may be misdiagnosed as benign lymphoid lesions are described and illustrated in this review. Differential diagnoses are considered, and the use of specialized techniques in diagnostic pathology are discussed. The four lymphomas selected for review include follicular lymphoma, mantle cell lymphoma with mantle zone pattern, interfollicular Hodgkin's disease, and nodular lymphocyte predominance Hodgkin's disease. PMID- 7770678 TI - Malignant thymic neoplasms that may mimic benign conditions. AB - The thymus is a complex, highly specialized organ that is derived from the third and fourth pharyngeal pouches and contains elements that originate from all three germinal layers. As such, it shows certain specific and distinctive reaction patterns to injury that are frequently encountered in a variety of reactive and inflammatory conditions. These reaction patterns, however, can also often be associated with neoplastic diseases arising from this organ, and in some instances, their presence may contribute to obscure the malignant nature of the underlying process. We present a review of the main tumor entities that may be mistaken for benign conditions of the thymus, with emphasis on the three major reaction patterns to injury that may be associated with malignant neoplasms of this organ: prominent cystic changes, stromal fibrosis, and reactive and hyperplastic changes of thymic epithelium. Histologic clues helpful for diagnosis and the differential diagnosis of these lesions are discussed. PMID- 7770677 TI - Soft tissue sarcomas that mimic benign lesions. AB - Although it is well known that a variety of benign mesenchymal neoplasms and reactive proliferations may mimic sarcomas, the fact that some types of sarcoma commonly are misinterpreted as benign is less widely appreciated. This review considers five such lesions in soft tissue: low grade fibromyxoid sarcoma, low grade myxofibrosarcoma (myxoid "MFH"), well differentiated liposarcoma (atypical lipoma), epithelioid sarcoma, and so-called inflammatory fibrosarcoma. Principal reasons for their underrecognition are their generally bland cytology, often relative hypocellularity, and indolent clinical course. Common to several of these lesions, however, is a tendency for histological and hence biological progression in local recurrences, underlining the importance of accurate diagnosis and adequate treatment of the primary lesion. This review considers the principal clinicopathologic features, differential diagnosis and (where appropriate) nosologic status of this treacherous group of neoplasms. PMID- 7770679 TI - [Hormone substitution following a gynecological cancer]. PMID- 7770680 TI - [Can tamoxifen prevent breast cancer?]. PMID- 7770681 TI - [Hormone substitution following breast cancer: caution]. PMID- 7770682 TI - [Diagnostic approach to precocious puberty]. PMID- 7770683 TI - [Gynecologic endocrinology of the adolescent. Basic management and gynecological endocrinology in adolescents]. PMID- 7770684 TI - [Role of echography and Doppler flowmetry in the diagnosis of ovarian masses]. PMID- 7770685 TI - [Diagnosis and treatment of mastodynia]. AB - Breast pain or mastalgia is a frequent complaint and it may represent various pathological conditions. After a thorough evaluation and reassurance of the patients, only those whose symptoms are severe enough to alter their life-style still require therapy. In some cases it will be indicated to modify or to stop an oral contraception or to adapt a hormone replacement therapy. Those women still resistant to treatment may experience relief from evening primrose oil supplements, bromocriptine, danazol, some progestins, tamoxifen or GnRH analogues. Therapy of non cyclic breast pain is made according to the underlying pathology. If no substrate is present, treatment is the same as for cyclical mastalgia but the response is diminished. PMID- 7770686 TI - [Importance of the thyroid before, during and after pregnancy]. PMID- 7770687 TI - [Diagnostic and therapeutic approach to hyperprolactinemia]. PMID- 7770688 TI - [Prospective study of abuse treatment. Lausanne, 1994]. PMID- 7770689 TI - [Informed consent in the framework of biomedical research: a survey]. AB - Inquiry on the quality and steps taken to obtain informed consents for biomedical research projects, based on the cases of 39 patients coming from 15 different projects with immediate therapeutic goals and 16 healthy subjects coming from 4 different projects without immediate therapeutic goals. Comparison between observed reality and the more or less demanding norms that were recommended. We noted a much bigger gap (therefore a consent actually informed in a lesser way) in the group of patients than in the group of healthy subjects. Explanatory hypotheses: the healthy subjects' higher social and cultural level, but also the investigators' difficulty and comprehensible discomfort to integrate, with respect to the patient, the essentially different and possibly contradictory points of view of scientific research and medical care; the "double market" notion. PMID- 7770690 TI - [Paraneoplastic subacute sensory Denny-Brown neuronopathy or anti-Hu syndrome: a classical paraneoplastic syndrome]. AB - Paraneoplastic syndromes, or the remote non metastatic effects of cancer, are wellknown entities that may affect any organ or tissue in the body, including the central nervous system. Some have been shown to be associated with autoantibodies against the nervous system. One typical example ist the subacute sensory neuronopathy of Denny-Brown, classically associated with small cell lung cancer. These patients present with the subacute onset of a sensory neuronopathy which may appear as much as one year before the primary tumour is detected. An antibody called anti-Hu has been found in the serum in these patients, which recognizes a neuronal protein called Hu (M.W. 30 to 40 kD). This antibody can currently be detected by a combination of immunological methods such as Western blot analysis or immunohistochemistry. PMID- 7770692 TI - [Why history of medicine?]. PMID- 7770691 TI - [Which fly has bitten? Apropos of skin lesions induced by Simulium]. PMID- 7770693 TI - [Recollection of an assistant of Professor Cesar Roux]. PMID- 7770694 TI - [National Gastroenterology Week. Postgraduate Course and Annual Congress of the Mexican Association of Gastroenterology. Guadalajara, Jalisco, December 11-16, 1994. Abstracts]. PMID- 7770695 TI - Proliferating cell nuclear antigen staining of Fischer-344/N rat spleens affected by large granular lymphocyte leukemia. AB - Large granular lymphocyte (LGL) leukemia commonly occurs in the Fischer-344/N rat. The high spontaneous incidence complicates the interpretation of results from chronic carcinogenicity studies that use this rat strain. As a result, a comprehensive characterization of LGL leukemia is necessary to help understand the leukemogenic process and the applicability of staging for assessing the progression of this disease. In the current study, the proliferation rate of LGL leukemia cells from untreated control Fischer-344 (F-344) rats in 3 stages of leukemia compared to nonleukemic age-matched rats was determined by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). In histologic sections of spleen from aged F-344/N rats affected by LGL leukemia, there was a significant increase of both PCNA labeling and mitotic indices that was most advanced in the spleen of rats with more severe LGL leukemia. These results support biological significance for the morphologic staging system currently in use. PMID- 7770696 TI - Pathology and incidence of amelanotic melanomas of the skin in F-344/N rats. AB - A total of 121 spontaneous amelanotic melanomas of the skin were identified in 70 of 11,171 male and 51 of 10,927 female Fischer-344/N rats in 63 2-yr carcinogenicity studies conducted by the National Cancer Institute's Carcinogenicity Testing Program/National Toxicology Program. Amelanotic melanomas had characteristic anatomical locations and histologic features distinguishable from Schwann cell tumors. Of the 121 tumors, 84, 19, 10, and 8 cases occurred in the pinna, eyelid, scrotum, and perianal region (anus and tail), respectively. Amelanotic melanomas originated from the dermis and consisted of spindle cells arranged in an interlacing fascicular pattern often with a perivascular orientation; epithelioid cells were rarely seen. Only the tumors arising in the pinna metastasized to the lung and/or mandibular lymph nodes. The metastatic rate was 19% (16/84) of the tumors and was clearly increased with an increase in tumor size. Most metastasizing tumors had focal areas consisting of anaplastic spindle cells with an increased number of mitosis. The tumor cells stained positive for S 100 protein but negative for melanin. Ultrastructurally, the tumors were diagnosed as amelanotic melanomas based on the identification of numerous, intracytoplasmic premelanosomes without melanin formation in the tumor cells which were not enveloped by pericytoplasmic basal laminae. One localized amelanotic melanoma of the pinna was successfully transplanted to the subcutaneous tissue in the flank of 3 Fischer-344/N rats. PMID- 7770697 TI - Comparative 90-day feeding study with low-viscosity white mineral oil in Fischer 344 and Sprague-Dawley-derived CRL:CD rats. AB - A 90-day study was conducted to compare the effects of dietary administration of a food-grade white oil in female Fischer-344 (F-344) and Sprague-Dawley-derived (CRL:CD) rats. Animals were fed a low viscosity (15 mm2/sec at 40 degrees C) paraffinic white oil (designated as P 15[H]) at 0, 0.2, or 2.0% of the diet for 30, 61, or 92 days. There were no significant adverse clinical observations or unscheduled deaths. In the F-344 rats, occasional treatment-related changes were seen in hematology and clinical chemistry parameters. At necropsy, mesenteric lymph nodes were enlarged, and there was an increase in absolute and relative liver, mesenteric lymph node, and spleen weights as compared to controls. Histopathologic effects included hepatic and mesenteric lymph node microgranulomas and mesenteric lymph node histiocytosis. In CRL:CD rats, the only effects noted were accumulations of chronic inflammatory cells in the liver at the high dose only, without the formation of discrete microgranulomas. A dose related increase in mineral hydrocarbon (MCH) material in the liver and mesenteric lymph nodes was observed in both F-344 and CRL:CD rats. Although increased, liver MhC content was significantly less (approximately 50%) in CRL:CD rats than the levels detected in the F-344 rats. Mesenteric lymph node MHC levels did not differ significantly between the strains. This study demonstrated strain differences among rats in histopathologic effects of white oil, with the CRL:CD rat essentially showing no response compared to the F-344 rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770699 TI - Suppressive effect of beta-carotene on the development of pulmonary foam cells in rats with hyper beta-lipoproteinemia. AB - The effect of beta-carotene (BC) on the development of pulmonary foam cells (PFCs) was studied in rats with diet-induced hyper beta-lipoproteinemia. Rats were fed a standard diet; a hyper-beta-lipoproteinemia diet (HB) consisting of the standard diet, 4% cholesterol, and 1% cholic acid; or the standard diet plus 0.1% BC; or the HB diet plus 0.1% BC diet (HBC). Rats in the HB and HBC groups developed hyper-beta-lipoproteinemia, but no significant differences were observed in serum levels of total cholesterol, phospholipid, and beta- lipoprotein (B-LP) between both groups. The percentages of foamy, lipid-ingested monocytes (FMs) to the number of blood monocytes (BMs), the number and size of lipid droplets in FMs, the percentages of PFCs to the number of alveolar macrophages from bronchopulmonary lavage fluid, and the score of PFC development in the lungs of rats in the HBC group were reduced compared to those of rats in the HB group. There were no differences in latex-phagocytotic activity of BMs among rats in the control, HB, BC, and HBC groups. BC suppressed the foamy transformation of BMs and development of PFCs deriving from the influx of FMs into the alveoli of hyper-beta-lipoproteinemic rats. Based on the present results, it is presumed that the antioxidative property of BC may prevent an oxidative modification of B-LP under the hyper-beta-lipoproteinemic condition, leading to a decrease in the uptake of oxidatively modified B-LP by BMs. PMID- 7770700 TI - A simple method for performing routine histopathological examination of the cardiac conduction tissue in the dog. AB - In standard toxicity studies, the cardiac conduction tissue is not systematically sampled and examined for histopathological changes. Most methods described use serial sectioning perpendicular to the long axis of the sinoauricular node (SAN) and atrioventricular node (AVN). Dozens of slides are needed to allow examination of a significant portion of the SAN and AVN. A simple method was developed to be used in routine histopathologic examination of the dog heart. With a plane parallel to the external wall and the upper edge of the right auricle, the SAN and its arterial supply were easily sectioned and examined. The frontal plane parallel to the interventricular crest was the most appropriate plane for observing a large portion of the AVN and the bundle of His. Based on these results, the heart of 240 dogs from toxicology studies were successfully sampled and processed utilizing this technique. An average of 5 slides per node was needed to perform a satisfactory examination of each of the SANs and AVNs. PMID- 7770698 TI - Changes associated with long-term oral administration of the penem antibiotic FCE 22891 to rats and monkeys with particular emphasis on the urinary tract and the urine. AB - FCE 22891, a synthetic beta-lactam antibiotic of the penem class, was administered by gavage to Sprague-Dawley rats and cynomolgus monkeys for 26 wk (with and without a 6-wk recovery). Rats received the test material at doses of 0, 200, 500, and 1,250 mg/kg/day, and monkeys were given doses of 0, 100, 200, 400, and 600 mg/kg/day. At the end of the 26-wk treatment period, approximately two-thirds of the animals (both species) were sacrificed, and the remaining animals were held without treatment for a further 6 wk. A treatment-related mortality occurred in female monkeys receiving 600 mg/kg. There was a reduction in body weight gain in the high-dose groups of both species. Male rats were more affected than the females and, conversely, female monkeys were affected more than the males. At higher dose levels, both species exhibited an early, but transient, azotemia and oliguria with an increase in specific gravity and reduced pH. In rats, microscopic examination revealed treatment-related renal cortical tubular degenerative and regenerative changes with associated interstitial inflammation and fibrosis and diffuse urothelial hyperplasia in the urinary bladder. In general, female rats were less severely affected, and in both sexes there was a trend to recovery of most of these effects. In monkeys given 600 mg/kg of the test material, renal cortical tubular degeneration was seen only in those females that died in the first 5 wk of dosing. In other animals at this dose level, the renal lesions were determined to be reversible. PMID- 7770701 TI - Establishment of an animal model for pulmonary fibrosis in mice using monocrotaline. AB - A preliminary attempt at experimental induction of pulmonary fibrosis in which male ICR mice received 15 weekly sc injections of 200 or 100 mg/kg monocrotaline (MC) revealed that most animals treated with the larger dose died of severe interstitial pneumonia, whereas those given 100 mg/kg exhibited only relatively slight lung injury. Based on these results, male mice were administered sc injections of 200 and 100 mg/kg MC once a week for 9 and 18 times, respectively, and then maintained without any further treatment until week 28 after the start. Mice treated with 200 mg/kg MC showed severe pulmonary damage and died by week 25. Mortalities also occurred in the 100-mg group from week 16, with 11 of 40 animals surviving at the termination of the experiment. Histologically, both dose groups demonstrated severe interstitial pneumonia and/or pulmonary fibrosis. Ultrastructurally, inflammatory edema possibly attributable to injuries of alveolar capillary endothelial cells was observed in the high-dose group at week 8, and there was a remarkable increase in collagen fibers in alveolar septa in this group thereafter. The present study results suggest that lung injuries induced by MC treatment progress to irreversible lung fibrosis and that this animal model may have advantage for studying the pathogenesis of lung cancers in patients with pulmonary fibrosis. PMID- 7770704 TI - Interstitial cell adenoma of the rat testis: why is it such a problem in toxicology studies using Sprague-Dawley rats? AB - Arbitrary criteria can give unreliable diagnoses. Conditions that occupy the same marginal diagnostic space, such as interstitial cell hyperplasia and interstitial cell adenoma, sometimes will be mistaken for one another. When the true prevalence is low, the risk of false positives, as a percentage of all positives, is high. The preceding analysis predicts that, with currently recommended diagnostic criteria, any compound that causes nonneoplastic interstitial cell hyperplasia will be interpreted to cause interstitial cell neoplasia if SD rats are used and only microscopic diagnoses are considered. Conversely, the analysis predicts that no compound that actually causes neoplasia in interstitial cells will be identified as an interstitial cell tumorigen if F-344 rats are used and only microscopic diagnoses are considered. These predictions are consistent with experience. PMID- 7770703 TI - Electron microscopic study on the effect of alternate-day hydrocortisone therapy on lymphocyte populations in rat spleen and lymph nodes. AB - The ultrastructural effects of 400 mg/M2/day of hydrocortisone sc, given alternatively from day 7 through day 19, were studied on the lymphocyte populations in the white pulp of the spleen and in the cortex of the mesenteric lymph nodes of the immunologically immature rat. Results were consistent with both a direct lytic effect of hydrocortisone on small lymphocytes of the nodular cortex of the mesenteric lymph nodes and an indirect effect on small lymphocytes of the periarterial lymphatic sheath (PALS) of the spleen supplied via the thymus. In contrast, medium-sized lymphocytes in the PALS appeared to be unaffected by hydrocortisone, while medium-sized lymphocytes of the nodular cortex of the mesenteric lymph nodes exhibited a temporary depletion of cytoplasmic organelles. Hydrocortisone appeared to depress protein synthesis in these latter cells. The decrease in numbers of lymphoblasts and plasmablasts observed in the nodular cortex of the mesenteric lymph nodes and the white pulp of the spleen is consistent with hydrocortisone interference with proliferation and differentiation of activated B cells. PMID- 7770702 TI - Histopathological and ultrastructural changes in the juxtaglomerular apparatus of the rat following administration of ZENECA ZD6888 (2-ethyl-5,6,7,8-tetrahydro-4 [(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)- methoxy]quinoline), an angiotensin II antagonist. AB - Male and female Alderley Park rats were treated for 26 wk with ZENECA ZD6888, an angiotensin II (AII) antagonist, at doses of 25, 50, and 250 mg/kg/day and the kidneys examined by light and electron microscopy. Nephropathy (tubular degeneration and regeneration), thickening of the basal lamina, mononuclear cell infiltration, and hypertrophy and hyperplasia of the juxtaglomerular apparatus were seen by light microscopy. Ultrastructurally, juxtaglomerular cell granules were increased in number and displayed substantial structural heterogeneity. In some cells, granules contained paracrystalline inclusions while others consisted predominantly of myelinic debris. Evidence of conversion of arteriolar smooth muscle cells into juxtaglomerular cells and their degeneration was also obtained by electron microscopy. The juxtaglomerular changes were treatment- and dose related and were attributed to an exaggerated pharmacological action of the compound, that is, ZD6888-mediated blockade of AII receptors leading to competitive inhibition of the AII-mediated release of renin. The resemblance between the findings seen in the present study following administration of an AII antagonist and those due to angiotensin-converting enzyme inhibitors reported by others was striking. PMID- 7770705 TI - Hepatocyte transplantation: a potential treatment for acute liver failure. PMID- 7770706 TI - Effects of Nissen fundoplication on gastro-oesophageal reflux and oesophageal motor function. AB - BACKGROUND: Nissen fundoplication reduces gastro-oesophageal reflux effectively, but the mechanisms through which this effect is brought about have remained rather obscure. METHODS: In this study the effect of fundoplication on oesophageal acid exposure, oesophageal body motility, and lower oesophageal sphincter pressure (LOSP) was assessed prospectively. Eleven patients were studied before and 3 months after a floppy Nissen fundoplication. A Dent sleeve was used to measure LOSP, and ambulatory pH and pressure monitoring were used to evaluate oesophageal motor function. RESULTS: Gastro-oesophageal reflux was significantly decreased after fundoplication without an increase in LOSP. The motor function of the oesophageal body was not affected by the antireflux procedure. CONCLUSIONS: Nissen fundoplication is an effective antireflux operation, even though the procedure does not increase LOSP, and the motility pattern of the oesophageal body is not affected by the construction of a floppy fundic wrap. PMID- 7770707 TI - Parietal cell kinetics after administration of omeprazole and ranitidine in the rat. AB - BACKGROUND: This study aimed at determining the turnover rate of parietal cells after inhibition of acid secretion. METHODS: Rats were given omeprazole (80 mumol/kg) by gavage once daily or ranitidine (1200 mumol/kg) by osmotic minipump for 5 days. Control rats received saline only. All rats were also given 3H thymidine by osmotic minipumps. The animals were killed, 5, 14, 28, or 56 days after the start of the 3H-thymidine infusion. After formaldehyde fixation by perfusion through the aorta, light microscopic autoradiography was carried out on plastic sections of the oxyntic mucosa to determine the labeling index of the parietal cells. RESULTS: The average turnover rate in the control rats was calculated to be 0.61% per day, corresponding to a mean turnover time of 164 days. In the rats given inhibitors of acid secretion, the turnover rates did not differ significantly from those of the control group. CONCLUSION: Inhibition of gastric acid secretion did not significantly change the turnover rate of the parietal cells. PMID- 7770708 TI - Lansoprazole versus omeprazole in active duodenal ulcer. A double-blind, randomized, comparative study. AB - BACKGROUND: Lansoprazole is a new substituted benzimidazole that inhibits the H+,K(+)-adenosine triphosphatase in the parietal cell and, like the first developed proton pump inhibitor omeprazole, gives a strong inhibition of gastric acid output. METHODS: In this double-blind randomized comparative study patients with active duodenal ulcers were treated with either 30 mg lansoprazole or 20 mg omeprazole in the morning. All demographic data in the two treatment groups were comparable. RESULTS: A total of 279 patients entered the study. There was no difference in healing rates between the groups either after 2 weeks (86.2% for lansoprazole and 82.1% for omeprazole) or after 4 weeks (97.1% and 96.2%). No patient ceased treatment owing to side effects. CONCLUSIONS: Both lansoprazole and omeprazole generate very high healing rates and good symptom relief in active duodenal ulcer. Side effects are few and mild. PMID- 7770709 TI - Omeprazole and dry mouth. AB - BACKGROUND: Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy. METHODS: We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes. RESULTS: Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus. CONCLUSION: Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous. PMID- 7770710 TI - Effects of insulin and beta-adrenergic blockade on the migrating motor complex in humans. AB - BACKGROUND: Interdigestive small-intestinal motility is suppressed by hyperglycemia and also by hyperinsulinemia per se. Since hyperinsulinemia may increase sympathetic activity, the present study was undertaken to ascertain to what extent insulin affects phase III of the migrating motor complex (MMC) and MMC-related duodenal retroperistalsis and whether beta-adrenergic receptors may mediate the effects of insulin. METHODS: Fasting motility was studied in eight healthy volunteers on three occasions with an eight-lumen perfused pressure catheter, with closely spaced recording points in the proximal duodenum. On the control day 5-h antroduodenojejunal manometry was performed. On another study day euglycemic hyperinsulinemic clamping was performed for 2 h after an initial basal recording. On a 3rd day motility was recorded during propranolol infusion, combined with a period of euglycemic hyperinsulinemia. RESULTS: During hyperinsulinemia complete absence of phase III of the MMC in the gastric antrum was observed, whereas 55% of the MMC had a gastric phase-III component on the control day. The duration of phase III in the proximal duodenum was decreased during hyperinsulinemia compared with the control period (p < 0.05). This inhibitory effect of insulin on the activity front was not prevented by beta blockade. Under control conditions the proportion of retroperistaltic pressure waves in the proximal duodenum was 13 +/- 8% in early phase III, increasing in late phase III to 79 +/- 15% (p < 0.01). Duodenal phase III during hyperinsulinemia showed a similar increase in retroperistalsis, from 4 +/- 4% in early phase III to 67 +/- 21% in late phase III (p < 0.01). The corresponding proportions during beta blockade were 16 +/- 10% and 86 +/- 14%, respectively. CONCLUSIONS: Hyperinsulinemia per se abolishes antral phase III and makes the duodenal phase III shorter but does not interrupt the distinct pattern of retroperistalsis in late phase III. Beta-adrenergic receptors seem not to be important for these effects of insulin or for the retroperistalsis in duodenal phase III. PMID- 7770711 TI - Lactose malabsorption in Khants in western Siberia. AB - BACKGROUND: We wanted to estimate the prevalence of selective lactose malabsorption (SLM) in Khants, a small Finno-Ugric population living in Western Siberia who have traditionally consumed no milk in adulthood. METHODS: A total of 80 Khants, aged 8-57 years and living on the middle reaches of the River Ob, were studied. The diagnosis was based on a lactose tolerance test; general malabsorption was excluded by a glucose-galactose tolerance test whenever possible. In six subjects electronmicroscopic examination of the duodenal mucosa was performed. RESULTS: The prevalence of SLM in the Khants was 94%. CONCLUSION: This is the highest prevalence found in the previous Soviet Union. PMID- 7770712 TI - Intestinal disaccharidase activity in human immunodeficiency virus disease. AB - BACKGROUND: The relationship between disaccharidase activity, progression of human immunodeficiency virus (HIV) disease, and diarrhoea and weight loss was investigated. METHODS: Forty-six HIV-positive patients ingested a solution of lactose, palatinose, sucrose, and lactulose after 24 h of dietary exclusion and overnight fasting, after which urine was collected for 10 h. Urinary disaccharide (activity) ratios-lactose/lactulose (L/LL), palatinose/lactulose (P/LL), and sucrose/lactulose (S/LL)-were measured by thin-layer chromatography. RESULTS: There was a significant decrease in disaccharidase activity (L/LL, P/LL, and S/LL) with advancing clinical stage of HIV disease (p < 0.05, Wilcoxon rank sum test) as well as decreasing CD4 count (p < 0.05, Spearman correlation). Patients with weight loss/diarrhoea also had significantly (p < 0.05) decreased disaccharidase activity compared with control but not as compared with AIDS patients. Anti-retroviral therapy did not influence disaccharidase activity. CONCLUSION: Impairment of disaccharidase activity occurs with advancing HIV disease, but its role in HIV patients with weight loss and diarrhoea remains to be determined. PMID- 7770713 TI - The presence of bicarbonate in oral rehydration solution does not influence fluid absorption in cholera. AB - BACKGROUND: On the basis of human perfusion studies it has been speculated that bicarbonate ions in oral rehydration salt solutions (ORS) to treat diarrhoea are more efficiently absorbed from the small bowel. We evaluated the role of bicarbonate in ORS by using a reduced purging rate in cholera as a proxy indicator for absorption efficiency in cholera-like severe diarrhoea. METHODS: In a double-blind randomized trial 60 patients received standard ORS containing bicarbonate or an identical solution except that sodium bicarbonate was replaced by an equimolar amount of sodium chloride (sodium, 90 mmol/l; potassium, 20 mmol/l; chloride, 80 mmol/l; bicarbonate, 30 mmol/l; glucose, 111 mmol/l; and osmolality, 331 mmol/l) after initial intravenous rehydration to correct initial dehydration and shock and until diarrhoea ceased. RESULTS: Five patients receiving standard ORS and eight receiving bicarbonate-free ORS required unscheduled intravenous therapy for recurrence of severe dehydration in spite of receiving ORS solution. ORS intake and purging rate, in ml/kg body weight/day, both including and excluding stool output during unscheduled intravenous therapy are closely similar in the two treatment groups. CONCLUSION: The results indicate that bicarbonate-containing ORS solution does not have any clinically significant effect on the absorption efficiency of ORS, either beneficial or adverse, and its use is relevant only for correction of metabolic acidosis of diarrhoeal dehydration. PMID- 7770714 TI - Trophic effects of biosynthetic growth hormone on normal and defunctioned left colon in rats. AB - BACKGROUND: In rats with diverting colostomies the effects of growth hormone can be differentiated from the actions of fecal passage. METHODS: After sham operation or diverting colostomy rats were treated with biosynthetic growth hormone (b-hGH) for 4 weeks. RESULTS: In defunctioned colon of b-hGH-treated rats there were increases in mucosal surface area and the weight of mucosa and muscularis propria compared with the atrophic colon of saline-treated rats. The breaking strength of defunctioned colon rings was greater and the defatted dry weight and hydroxyproline content of these specimens were also increased. In intact colon b-hGH stimulated luminal surface area, the weight of mucosal and submucosal layers, and the hydroxyproline content compared with controls. The breaking strength was highest in specimens from saline-treated rats. CONCLUSIONS: B-hGH has a growth-promoting role throughout the whole thickness of the colonic wall in rats also in the absence of fecal passage. PMID- 7770715 TI - Fasting breath hydrogen concentrations in gastric and small-intestinal bacterial overgrowth. AB - BACKGROUND: Although elevated fasting breath hydrogen concentrations have been reported in small-intestinal bacterial overgrowth, this diagnosis has been presumptive or based on definitions that vary from study to study. The influence of gastric bacterial overgrowth and gastroduodenal pH has not been documented. Conflicting evidence exists as to the reproducibility of breath hydrogen measurements. METHODS: Forty-two subjects underwent culture of gastric and duodenal aspirates. The pH was measured by indicator paper. Paired fasting breath hydrogen concentrations were measured by gas chromatography within 7 days of endoscopy. RESULTS: Paired fasting breath hydrogen concentrations differed in terms of normality or abnormality in 21% of subjects. Paired concentrations correlated significantly in overgrowth but not in culture-negative subjects. Sensitivity for bacterial overgrowth was 4-29%, and specificity 71-100%. No correlation with gastroduodenal pH was found. CONCLUSIONS: The clinical relevance of a single fasting breath hydrogen concentration is limited. The efficacy of paired measurements for gastric or small-intestinal bacterial overgrowth is poor. PMID- 7770716 TI - DNA aneuploidy in gastric carcinoma. Flow cytometric data related to survival, location, and histopathologic findings. AB - BACKGROUND: The aim of the study was to evaluate the prognostic significance of DNA ploidy of gastric carcinomas. METHODS: The DNA content was analyzed by flow cytometry on archival paraffin-embedded material from tumors of 97 consecutive patients. RESULTS: A multivariate analysis showed that the DNA ploidy pattern and lymph node metastasis were the only independent prognostic markers for survival (p = 0.01 and p = 0.02, respectively). The relative risk of death due to gastric cancer was three times greater for patients with DNA hypertetraploid tumors than for patients with DNA diploid tumors and twice as high for patients with lymph node metastasis as for patients without. Well and moderately differentiated carcinomas were more frequently aneuploid than tumors with poor differentiation (p = 0.047). There was no correlation between tumor ploidy pattern and location. In univariate analysis tumor growth through the serosal wall was predictive of poor survival (p = 0.003). CONCLUSIONS: DNA ploidy is an independent prognostic indicator for cancer-specific survival in gastric cancer. PMID- 7770717 TI - Comparison of immunomodulative effects of the histamine-2 receptor antagonists cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells in gastric cancer patients. AB - BACKGROUND: Histamine-2 receptor antagonist (H2-RA) have been shown to improve the function of various parts of the immune system. The proposed mechanism of the immunomodulative effects of H2-RA has been considered to be the inhibition of suppressor T-lymphocyte activity, an increase in interleukin-2 production, and an enhancement of natural killer cell activity. Most of these studies were done with cimetidine. Comparative data with other H2-RA are limited and conflict on immunomodulative effects. Comparison of the actions of H2-RA on the immune system is required. METHODS: We compared the immunodulative effect of the H2-RAs cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells (PBMC) in normal controls and patients with gastric cancer. DNA synthesis, cytotoxicity against K562 cells, and the levels of soluble interleukin-2 receptor (sIL-2R) in supernatant were measured after addition of the various H2-RA to PBMC cultures. RESULTS: Subjects with gastric cancer showed significantly higher levels of suppressor lymphocyte activity than normal controls. These levels were restored to levels of normal controls by the addition of cimetidine. Statistically significant lymphoblastogenesis and cytotoxicity against K562 cells were observed only in cimetidine-treated PBMC (p < 0.05); such effects were not observed in ranitidine- or famotidine-treated PBMC. Significantly increased levels of sIL-2R were found in supernatants obtained from culture flasks treated with cimetidine and phytohemagglutinin or ranitidine and phytohemagglutinin (p < 0.01). CONCLUSIONS: Of the three H2-RAs tested, cimetidine had the strongest and famotidine the weakest immunomodulating effect. Only cimetidine augmented the cytotoxicity and proliferative response of lymphocyte to mitogen; neither ranitidine nor famotidine had such an effect. These results might be due to their structural differences. In addition, the immunologic effects of H2-RA are unlikely to be mediated via specific interaction at the H2 receptor. PMID- 7770718 TI - Septic acute cholecystitis. AB - BACKGROUND: Bacteremia occurs frequently in cholangitis, but the incidence of bacteremia in acute cholecystitis has not previously been examined. METHODS: Seventy-eight cases (46 men and 32 women; mean age, 63 +/- 10 years) of acute cholecystitis with positive blood cultures were analyzed for clinical manifestation, bacteriology, and what consequences ensued. Seventy-eight non bacteremic cholecystitis patients, matched for age and sex, served as the control group. RESULTS: The prevalence of bacteremia in acute cholecystitis was 7.65% (78 of 1020). A single microorganism was isolated from the blood and bile in 87.2% and 27.3%, respectively. The commonest organisms were Escherichia coli and Klebsiella pneumoniae. The source of bacteremia could be identified from the infected bile in 80% of cases. Compared with the non-bacteremia group, significant increases in liver biochemical test results (aspartate and alanine aminotransferases and bilirubin, and so forth), more complications (acute renal failure and septic shock), and higher mortality (9.0%) were found in the bacteremic group. CONCLUSION: Acute cholecystitis is not often complicated by bacteremia, but when bacteremia is present, morbidity and death more consistently ensue. PMID- 7770719 TI - Small colorectal polyps. PMID- 7770720 TI - The two-signal model and 'self'-reactivity: are they really incompatible? PMID- 7770721 TI - Natural killer suppressor factors in sera from HIV-infected subjects. AB - We investigated the presence of NK suppressor factors in HIV+ sera. We further investigated if gp120 could be one of the substances responsible for the impairment of NKC regulation found in HIV+ asymptomatic patients. Our results indicate that HIV+ sera inhibit significantly normal NKC in a dose-dependent way, even at concentrations as low as 1%. The inhibitory effect of HIV+ sera decreased, but was not completely removed, by adsorptions of IgG or by treatment with a MoAb against human FcIgG. Pretreatment of normal effector cells with anti CD16 MoAb slightly reduced their cytotoxic capability, but did not modify the suppressor effect of HIV+ sera. The The preincubation of normal PBMC with recombinant gp120 had also a suppressor effect even at 10 ng/ml. Pretreatment of HIV+ sera with anti-gp120 or anti-FcIgG MoAb reduced, but not completely, their inhibitory effect. In conclusion, HIV+ serum has a dose-dependent inhibitory effect on normal NKC. Most of this inhibition is caused by IgG, but other substances, such as gp120, can also contribute to it. Since the removal of IgG and further treatments of HIV+ sera were not able to abrogate completely the NK suppression, other serum factors still undetermined (TNF-alpha, other cytokines), should be considered. PMID- 7770722 TI - A correlation between the expression of the bcr-abl chimeric gene and severity of the clinical state of CML patients with time. AB - Using the reverse polymerase chain reaction, four Ph' positive CML patients were followed for 2 years; a correlation between the severity of the clinical state and the b3a2 expression was noted with time. Additionally, amplification of the c myc proto-oncogene was observed, using Southern blot analysis, in one patient prior to his entry to the blast phase. No reorganization of the bcr-abl rearrangement site was found in the latter patient. The data suggest that a routine follow-up of CML patients using the Southern blot analysis and the reverse transcription-polymerase chain reaction might be of importance in evaluating the progression of the disease. PMID- 7770723 TI - Opposing effects of interleukin-10 on mouse macrophage functions. AB - Interleukin (IL)-10 generally is considered a macrophage deactivating factor and thus inhibits the cell-mediated responses against intracellular parasites. We evaluated the in vitro effects of IL-10 on three different parameters of macrophage function. We found that IL-10 inhibited gamma interferon (IFN-gamma) priming for enhanced O2- release of mouse bone marrow-derived macrophages but had opposing effects on NO2- secretion according to the sequence of the treatment with IL-10 and the agonists of NO2- secretion. Likewise, IL-10 was able to induce a small but consistent degree of bacteriostasis of Mycobacterium avium and, also, to inhibit the bacteriostasis induced by IFN-gamma. Thus, we show that, according to the timing of exposure of macrophages to stimulating and inhibiting cytokines and agonists of their functions, IL-10 shows different effects on macrophage function. PMID- 7770724 TI - Chemospecificity and cross-reactivity of target cell recognition by human CD56+ NK and LAK cells. AB - Inhibition of specific cytotoxicity of highly purified (> 95%) human CD56+ NK and LAK cells against K562 tumour cells was studied with various sugar acetates. Maximum inhibitory specificity was obtained with 60%-deacetylated penta-acetates of mannose, galactose, glucose, or 80%-deacetylated penta-O-acetate of N-acetyl neuraminic acid. The inhibition was strictly dosedependent and 100% inhibition was achieved in the concentration range of 500-1000 nmoles/ml with all four sugar acetate samples. Enhancement of specific cytotoxicity in the presence of rhamnogalacturonan (RG; 500 ng/ml), acting as a bridging molecule, was also inhibited in a dose-dependent manner with the same inhibitory specificity and within the same concentration range indicating involvement of the same number of sugar acetate-specific receptors. Moreover, formation of lytic CD56+ effector cell/tumour cell (E/T) conjugates was equally well inhibited whereas formation of total E/T conjugates was only partially inhibited (NK: 44-73%; LAK: 46-50%). E/T conjugate formation in the presence of RG was enhanced. Inhibition of the enhancement of formation of lytic E/T conjugates in the presence of RG was again completely accomplished with the same inhibitory specificity and within the same concentration ranges as recorded for E/T conjugate formation in the absence of RG. However, inhibition of total E/T conjugate formation was again only partially achieved at the given concentrations. The data support the assumption of an NK cell receptor with specificity for acetylated carbohydrate moieties on target cells or on bridging molecules such as RG. PMID- 7770725 TI - Expression of the human mucosal lymphocyte antigen, HML-1, by T cells activated with mitogen or specific antigen in vitro. AB - Expression of the human mucosal lymphocyte antigen, HML-1 (CD103), recently identified as a novel alpha E beta 7 integrin, was studied on peripheral blood lymphocytes activated with mitogen or specific antigen. HML-1 was up-regulated on PHA activated T-lymphoblasts cultured in 100IU/ml interleukin-2 (IL-2), reaching a peak of > 50% positive cells at day 7, and expression was maintained at this level throughout the 28-day culture period. Following a transient decrease in the percentage of L-selectin cells, expression of this molecule was maintained on most PHA T-lymphoblasts. Cells activated by purified protein derivative of M. tuberculosis (PPD) or in mixed lymphocyte culture also up-regulated and maintained HML-1 expression for 14 days. In contrast, in all cases the percentage of CD25+ cells rose initially but subsequently declined over the same time periods. When freshly isolated cells from tonsil, spleen, mesenteric lymph node and lung were analysed, only lung contained significant numbers (39 +/- 6%) of HML-1+ cells. In both freshly isolated and activated cell populations the great majority of HML-1+ cells co-expressed CD8 although some HML-1+ CD8- cells were also present. Production of TGF-beta 1 peaked early during T-lymphoblast and MLR cultures and was not related to induction of HML-1 expression. Immunoprecipitation studies showed that the HML-1 molecule expressed on 10-day PHA T-lymphoblasts was indistinguishable from that found on intestinal intraepithelial lymphocytes and that no alpha 4 beta 7 integrin was expressed by these cells. Although HML-1 expression is essentially restricted to mucosal leucocytes in vivo, these experiments show that it is readily induced and maintained along with co-expression of L-selectin following CD8+ T-lymphocyte activation in vitro. PMID- 7770726 TI - Cytotoxic potency of CD22-ricin A depends on intracellular routing rather than on the number of internalized molecules. AB - Cytotoxicity of immunotoxins (ITs) varies considerably depending on factors like the capability of the target antigen to internalize IT molecules, intracellular processing and routing of the IT. We studied factors that may influence cytotoxicity of CD22-ricin A IT to several B cell lines. The antigen density varied from 5.9 x 10(3) to 6.0 x 10(4) molecules/cell. The ID50, determined by protein synthesis inhibition, varied from 2.1 x 10(-12) to 3.8 x 10(-11) M IT in absence and from 2.8 x 10(-14) M to 5.2 x 10(-12) M IT in presence of the cytotoxicity enhancer NH4Cl (6 mM). In absence as well as in presence of NH4Cl no correlation could be found between antigen density and ID50. No relation was observed either with the rate of cytotoxicity. Even in cell lines with a low antigen density, such as KM3, protein synthesis was quickly inhibited. In order to investigate whether the cytotoxicity was dependent on the number of internalized molecules the kinetics of internalization and exocytosis of degraded 125I-labelled CD22 molecules were studied. After 24 h the number of internalized CD22 molecules was highest in Ramos (154,500), followed by Daudi (110,300) and KM3 (69,900). However, despite the higher internalization rate of Daudi the rate of cytotoxicity of 10(-8) M IT was comparable with KM3. NH4Cl did not influence the number of internalized molecules but postponed degradation of CD22. In conclusion, CD22-ricin A is a very potent and fast acting IT even for elimination of target cells that express low numbers of antigen. These results may have implication for treatment of different B cell malignancies with CD22-ricin A. PMID- 7770727 TI - In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: possible protection against amyloid fibril formation. AB - The effects of acid proteases on degradation of serum amyloid A protein (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), when incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited by an acid protease inhibitor, pepstatin. The degraded SAA molecules lacking nine or more amino-terminal residues, when exposed to in vitro fibril-forming conditions, failed to form Congo red positive precipitates and did not show amyloid fibril-like structure by electron microscopy. This suggests that the amino-terminal portion of SAA is essential for fibril formation. Cathepsin D, one of the lysosomal enzymes, also initiated degradation of rSAA1 at the amino-terminus. Cathepsin D immunoreactivity was detected in marginal areas of amyloid deposits in spleens from patients with reactive amyloidosis. These findings suggest that cathepsin D or similar acid proteases may be involved in SAA catabolism and may protect against amyloid formation. PMID- 7770728 TI - Human IgG rheumatoid factors and RF-like immune complexes induce IgG1 rheumatoid factor production in mice. AB - The synovial fluid of patients with rheumatoid arthritis (RA) was found to contain IgG and/or IgG-containing immune complexes (ICs) that stimulated an intense antibody formation when injected into mice of certain strains, notably of NZ background. The response was characterized by high and sustained levels of IgG1 antibodies with rheumatoid factor (RF) activity. In the study described, we investigated whether it is the antibodies with RF activity in the synovial fluid, that are responsible for stimulation of mouse RF in vivo. Different mouse strains were injected with synovial fluid from a seropositive RA patient (RA-SF), with human monoclonal antibodies with RF activity, with a human non-RF monoclonal antibody or with different preformed RF-like antibody-antibody (Ab-Ab) ICs. The experimental mice were monitored subsequently for IgG1 RF production. IgG1 RF antibodies were found in all strains (NZB, BALB/c and CBA) injected with Ab-Ab ICs formed at equivalence, but only in NZB using RA-SF or human monoclonal antibodies with RF activity. Optimal production of IgG1 RF by Ab-Ab ICs required the integrity of Fc and F(ab)'2 portions respectively of the antibodies; soluble and truncated ICs were less effective. Further studies demonstrated that the IgG1 RF response was not simply the result of a specific immune response against human IgG, since humoral immunity against human IgG was induced only when combined with an efficient adjuvant. During a typical adjuvant-associated primary response specific antibodies of IgM, IgG1 and IgG2a isotypes were found, i.e. quite different from the selective IgG1 response induced by RF-like containing immune complexes. This conclusion is substantiated further by the clear differences in responses to IgG containing fraction obtained from RA-SF in NZ mice compared to other strains. Our findings argue for a different type of reaction leading to the selective IgG1 response and might aid in elucidating the mechanisms for chronic production of antibodies with RF activity in patients with RA. PMID- 7770729 TI - Molecular analyses of anti-DNA antibodies induced by polyomavirus BK in BALB/c mice. AB - In the present experiments, two groups of BALB/c mice (five individuals in each group) were hyperimmunized through four consecutive immunizations with either BK virus (Group 1) or BK dsDNA complexed with methylated BSA (Group 2). All immune sera taken after the fourth immunization from both groups reacted strongly with polyomavirus BK dsDNA as well as with calf thymus dsDNA, and all sera contained antibodies that bound in the Crithidia luciliae assay. This indicates that polyomavirus BK was able to induce antibodies with binding characteristics similar to SLE anti-DNA antibodies. To further characterize these induced anti DNA responses, 10 monoclonal anti-DNA antibodies (four from Group 1, and six from Group 2) were generated and selected for reactivity with S1-nuclease digested CT dsDNA. Their specificity for BK and CT dsDNA molecules, as well as their light and heavy chain variable region cDNA nucleotide sequences were analysed to compare them with known SLE derived anti-DNA antibodies. All of the 10 antibodies bound strongly to BK dsDNA, while seven also bound to CT dsDNA in competitive ELISA experiments. V-region analysis revealed that the induced antibodies resembled anti-DNA antibodies characteristic for murine SLE, and all but one contained arginine in the VH CDR3 region. The arginines present in the monoclonal antibodies originated either from an RF shift from RF1-->RF3 of the D-genes or from N-sequence additions. Taken together, the data demonstrate that anti-DNA antibodies in response to hyperimmunization with polyomavirus BK have the same characteristics as of those occurring spontaneously in SLE. As virus infection/replication in vivo implies expression of immunogenic (non-self) DNA binding proteins that may render DNA immunogenic, the present results may therefore suggest one physiological mechanism for production of SLE-related anti DNA antibodies. PMID- 7770730 TI - Technical aspects of the determination of myeloperoxidase antibodies in systemic vasculitis. PMID- 7770731 TI - Gender differences in schizophrenia: hormonal effect or subtypes? AB - Compared with their male counterparts, females with schizophrenia, on average, show better premorbid functioning, later onset, and a more benign course of illness. They are also more likely to have a family history of schizophrenia and/or affective illness, to exhibit "atypical" and affective features, and to show a seasonal pattern of hospital admission that mimics that of patients with mania. However, there exists a paradox. Although schizophrenia in females has much in common with affective disorder, the "schizophrenogenic" effect of maternal influenza also appears to be more significant in female than in male schizophrenia. Perhaps females with a predisposition to affective psychosis who have also been subject to the effects of maternal viral infection during gestation develop some subtle neurodevelopmental damage that renders their psychosis schizophrenia-like. PMID- 7770732 TI - Abnormal photic driving responses in never-medicated schizophrenia patients. AB - The present study was conducted to compare electroencephalogram (EEG) driving responses to 10 hertz photic stimulation in 14 drug-naive schizophrenia patients and 16 sex- and age-matched control subjects. The amplitude of photic driving responses (PDRs) recorded from the occipital region was significantly lower in schizophrenia patients than in controls. In eight schizophrenia patients (vs. none in the control group) the PDR amplitudes recorded at the frontal region were higher than those at the occipital region, and frontal to occipital PDR ratios were significantly larger in schizophrenia subjects than in controls. Quantitative analysis of the resting EEG showed that the patients also had a significantly lower amplitude for the alpha frequency band. These findings suggest that the PDRs of schizophrenia patients are abnormal in their amplitude and distribution. PMID- 7770733 TI - Seasonality of birth in schizophrenia in Taiwan. AB - The phenomenon of seasonality of birth in schizophrenia is important to the study of the etiology of this mental disorder because it helps give directions for further research. Patients' hospital files from 1981 to 1991 at two of the largest hospitals with psychiatric wards in Taiwan were reviewed, and dates of birth were collected on 3,346 patients diagnosed with schizophrenia. After adjusting for the variations of the total monthly births in the population, an Auto-Regressive Integrated Moving Average model was applied. Results support a seasonality phenomenon and indicate a disproportional excess of births in schizophrenia in the cold months (November to February) compared with the hot months (May to August). These findings are compatible with many other studies in other countries and climates. Further investigations of season-related environmental factors in the etiology of schizophrenia are recommended. PMID- 7770734 TI - Multisite experimental cost study of intensive psychiatric community care. AB - A 2-year experimental cost study of 10 Intensive Psychiatric Community Care (IPCC) programs was conducted at Department of Veterans Affairs (VA) medical centers in the Northeast. High hospital users were randomly assigned to either IPCC (n = 454) or standard VA care (n = 419) at four neuropsychiatric (NP) and six general medical and surgical (GMS) hospitals. National computerized data were used to track all VA health care service usage and costs for 2 years following program entry. At 9 of the 10 sites, IPCC treatment resulted in reduced inpatient service usage. Overall, for IPCC patients compared with control patients, average inpatient usage was 89 days (33%) less while average cost per patient (for IPCC inpatient, and outpatient services) was $15,556 (20%) less. Additionally, costs for IPCC patients compared with control patients were $33,295 (29%) less at NP sites but were $6,273 (15%) greater at GMS sites. At both NP and GMS sites, costs were lower for IPCC patients in two subgroups: veterans over age 45 and veterans with high levels of inpatient service use before program entry. No interaction was noted between the impact of IPCC on costs and other clinical or sociodemographic characteristics. Similarly, no linear relationship was observed between the intensity of IPCC services and the impact of IPCC on VA costs, although the two sites that did not fully implement the IPCC program had the poorest results. With these sites excluded, the total cost of care for IPCC patients at GMS sites was $579 (3%) more per year than that for the control patients. PMID- 7770735 TI - Twins with schizophrenia: genes or germs? AB - High concordance for schizophrenia in monozygotic (MZ) twins is often cited as evidence for the etiological influence of genetics; however, even if twins are separated at birth, MZ twin concordance is influenced by the shared prenatal environment. Study of the placentation status of MZ twins provides a way to investigate some prenatal influences, including the possible role of viral infections. The probability of shared infections is likely to be greater in monochorionic MZ twin pairs than in dichorionic pairs because of shared fetal circulation in the monochorionic pairs. We drew from published twin studies and used reported concordance for handedness as a retrospective marker of placentation status. We found that MZ twin pairs with opposite-hand preferences were concordant for psychosis in 9 of 15 cases (60%), while only 18 of 56 twin pairs (32%) with same-hand preferences were concordant for psychosis. These results suggest that shared prenatal viral infection may account for much of the high concordance for schizophrenia in identical twins. PMID- 7770736 TI - Costs of schizophrenia in The Netherlands. AB - This study tries to identify and estimate the health care costs of schizophrenia in The Netherlands and to determine in a broader sense the total costs of schizophrenia for society in terms of productivity loss caused by absence from work and early retirement. The study can be described as a "cost-of-illness" study based on prevalence data. It shows that in The Netherlands about 2 percent of the total health care budget is spent on the treatment of schizophrenia patients. This figure is rather high, since the prevalence rate of schizophrenia in The Netherlands is only 0.6 percent. The indirect costs--production lost because of absence from work, disability, and early death--were very low, but these costs are underestimated because schizophrenia patients are unlikely to become active participants in the labor force. It is also difficult to identify people who have died of schizophrenia in national data because schizophrenia in itself is not lethal, but individuals with schizophrenia may die because of suicide or violent death. PMID- 7770737 TI - First person account: living in a nightmare. PMID- 7770738 TI - The multidimensionality of schizotypy. AB - We present an overview of self-report scales for measuring schizotypy and a review of factor-analytical studies of these scales. These studies show that schizotypy is a multidimensional construct consisting of three or four factors. Positive Schizotypy, Negative Schizotypy, Nonconformity, and possibly Social Anxiety/Cognitive Disorganization. Clinical and external validation studies provide support for the construct validity of the Positive Schizotypy and Negative Schizotypy factors, but as yet fail to support the Nonconformity and Social Anxiety/Cognitive Disorganization factors. In accordance with this multidimensional structure, the scales for measuring schizotypy can be classified as factor-specific scales. We consider the striking similarities between the multidimensionality of schizotypal traits and the multidimensionality of schizophrenic symptoms. We also look at the similarities and differences between schizotypy and normal personality traits. Some practical and theoretical implications of these relationships are discussed. PMID- 7770739 TI - A family study of schizotypal disorder. AB - Direct, blind interviews were used to study the risk for and prevalence of DSM III-R Axis I and II disorders in 93 first-degree relatives of outpatients with schizotypal personality disorder (SPD) and outpatients with other personality disorders. Risks for SPD (at a slightly loosened diagnostic threshold) and schizoid personality disorder were significantly higher in the families of probands with SPD. Schizophrenia was present only among relatives of probands with SPD, accounting for a morbid risk of 4.1 percent. Neither familial risks for mood and anxiety disorders nor the prevalence of other Axis II disorders significantly differed in the two groups of relatives. It is suggested that SPD is a familial disorder representing a phenotypic expression of liability to schizophrenia. PMID- 7770740 TI - Schizotypal personality disorder in parents and the risk for schizophrenia in siblings. AB - With on exception, previous studies examining the familial relationship between schizotypal personality disorder (SPD) and schizophrenia have compared rates of SPD in relatives of probands with schizophrenia versus control probands. In the Roscommon Family Study, an epidemiologically based family study of major psychiatric disorders conducted in the west of Ireland, we used a Cox proportional hazards model to examine the impact of a parental diagnosis of SPD on the risk for psychiatric disorders in siblings of probands with schizophrenia or schizophrenia spectrum disorders. In siblings of probands with schizophrenia or schizophrenia spectrum, a parental diagnosis of SPD significantly increased the risk for schizophrenia and schizophrenia spectrum disorders, but not for affective illness or anxiety disorders. These findings replicate our previous results from the Roscommon Family Study, further supporting the hypothesis that SPD has a substantial familial relationship with schizophrenia and other schizophrenia spectrum disorders, but not with affective illness. PMID- 7770741 TI - Assessment of the central dopaminergic index of plasma HVA in schizophrenia. AB - Under fasting conditions, the dopamine (DA) metabolite homovanillic acid (HVA) in plasma originates mainly from central DA neurons or from central and peripheral noradrenergic (NA) neurons. The latter source contributes, in addition to HVA, the norepinephrine metabolites, for example, 3-methoxy-4-hydroxyphenylglycol (MHPG). It has been shown in primates that the association between HVA and MHPG in plasma or urine under varying rates of NA metabolism can be used to obtain an estimate of the central DA neuronal contribution of HVA to plasma or urine. This estimate is called the central dopaminergic index (CDI). Two studies presented here examine the applicability of this model in schizophrenia patients. The results were consistent with the proposed model and suggested that only about 30 percent of the total plasma HVA concentrations in our patients were derived from central DA neurons. A convenient modification of this model is proposed for future studies. Since the CDI of plasma HVA is not likely to be confounded by NA activity, this tool may prove useful in disentangling the roles played by the DA and NA systems in schizophrenia. PMID- 7770742 TI - Reevaluation of the mesolimbic hypothesis of antipsychotic drug action. AB - Conventional neuroleptic drugs are thought to derive their antipsychotic efficacy through influences on the mesolimbic dopamine (DA) system. In contrast, motor side effects of these drugs are suggested to follow from influences on the nigrostriatal DA system. This conceptualization is based on the assumption that behaviors mediated by the mesolimbic DA system are involved in schizophrenia while behaviors controlled by the nigrostriatal system are not. In this article, it is argued that although assumptions about mesolimbic activities may indeed be correct, those concerning the nigrostriatal system certainly are not. This being the case, drugs with mesolimbic-specific activity may not have significant antipsychotic potency and probably will not be free of motor side effects. The current thrust of neuropharmacology, which emphasizes development of drugs with pharmacological specificity rather than anatomical selectivity, is more likely to generate new antipsychotic agents with a reduced risk of motor side effects. PMID- 7770743 TI - Trends in the inpatient care of persons with schizophrenia. AB - This report analyzes nationally representative data to examine inpatient services provided to persons with schizophrenia. The data are for patients admitted to general hospitals, private psychiatric hospitals, and State and county mental hospitals between 1970 and 1986 (weighted n = 860,637). The proportion of admissions diagnosed as having schizophrenia decreased from 21 percent in 1970 to 16 percent in 1986; this proportion decreased in public general hospitals and increased in private general hospitals. The rate of admissions for schizophrenia decreased in public general hospitals and State and county mental hospitals and increased in private general hospitals. The overall admissions rate decreased for whites with schizophrenia and increased for African-Americans, owing entirely to increased admissions of African-American males. Private general hospitals and State and county mental hospitals relied less over time on private insurance; the use of Medicare increased in both public and private general hospitals; and Medicaid use increased in private general hospitals. Further research on services for this population is necessary as a baseline for health care reform. PMID- 7770747 TI - Zoonoses in the world: current and future trends. AB - Zoonoses still represent significant health problems in many developed and developing countries. Whereas rabies, brucellosis, and echinococcosis will remain the major zoonotic diseases to be tackled in developing countries for the next 20 years, it is very likely that many developed countries will have eliminated these diseases by then. As observed repeatedly in the past few years, new zoonoses are, however, expected to emerge in the near future. Due to ever-increasing animal and human movements these new agents, whether originating from the southern or northern hemisphere, will most probably spread throughout the globe very quickly. It is very probable, in view of the foreseeable changes in the developed (e.g. population aging) and developing world (e.g. population growth, urbanization) or both (e.g. AIDS pandemic, environmental changes), that this trend will continue and even intensify. PMID- 7770746 TI - Annual meeting of the Swiss Society of Tropical Medicine and Parasitology. Leysin, 20-22 October 1994. Report and abstracts. PMID- 7770744 TI - Patients' assessment of treatment predicting outcome. AB - Using a visual analog scale, 34 schizophrenia patients receiving long-term treatment in community care rated the extent to which their treatment was right for them. We investigated whether these assessments would predict the duration of patient hospitalization during an initial followup period of 12 months and a longer followup period of 30 months. The duration of full and partial hospitalization was assessed by means of a hospitalization index. Patients who assessed their treatment more negatively had significantly higher hospitalization indices in the two followup periods. The predictive value of the patients' assessments of treatment was not explained by the influence of other variables. PMID- 7770748 TI - Human rabies: a continuing challenge in the tropical world. AB - More than 99% of all human rabies deaths in the world occur in tropical developing countries. In India alone, 30,000 to 50,000 people may die of rabies each year. The Lyssaviruses (Family Rhabdoviridae) include rabies and rabies related viruses, 3 of which have caused human disease. Rabies is a zoonosis, principally affecting domestic and stray dogs in most parts of Africa, Asia and Latin America. In North America, southern Africa, parts of the Caribbean and Europe, the principal mammalian reservoir species are wild carnivores. The pathogenesis, clinical features and differential diagnosis of rabies are discussed. The planning of rabies control strategies requires background information on the distribution and incidence of rabies in animals and the species involved. In some parts of the world, such as Latin American cities, most domestic dogs, even apparent strays, have an owner and can be immunized with conventional canine vaccines during well publicized campaigns. However, in areas such as India, where there may be a high proportion of stray domestic dogs without owners, and in those areas where wild mammals are the principal reservoir species, immunization may be possible using live attenuated or recombinant oral vaccines distributed in baits. In the poor tropical developing countries, unsatisfactory nervous tissue vaccines are still widely used. However, economical multisite intradermal regimens using tissue culture vaccines have proved effective and have begun to replace nervous tissue vaccines in some countries. PMID- 7770745 TI - Vulnerability to delusions over time in schizophrenia and affective disorders. AB - This research used a prospective longitudinal design to study differences in vulnerability to delusions over time in 234 subjects with schizophrenia, schizoaffective disorder, or bipolar or unipolar affective disorder. Patients were assessed at three successive followups over a 7- to 8-year period. Over 60 percent of the schizophrenia and schizoaffective patients assessed experienced delusional activity at one of the three followups. Over 60 percent of the patients who initially had psychotic affective disorders also showed posthospital delusional activity. Significantly more schizophrenia patients than psychotic affective-disordered patients experienced consistent posthospital delusional activity at three successive followups. Unlike the schizophrenia subjects, affective patients showed a significant reduction in delusions after the first followup. After the initial acute psychotic episode that led to hospitalization, psychotic bipolar and unipolar affective patients showed a traitlike vulnerability to episodic delusional activity over time, but schizophrenia patients were vulnerable to more severe delusional activity and to more frequently recurring or sustained delusions. The study results question the views of several major theorists on the importance, persistance, and prognostic significance of delusions in schizophrenia. PMID- 7770749 TI - [Babesiosis, a little-known zoonosis]. AB - Babesiosis or piroplasmosis is a common zoonotic disease among wild and domestic animals. Man can be infected by this hemoprotozoan parasite transmitted by ixodid ticks. More than 400 cases have been observed in the United States, but only 21 cases have been reported in Europe. The American form, caused by B. microti, ranges in severity from asymptomatic to prolonged severe illness. It is characterized by irregular fever and moderate hemolytic anemia. The European form, caused by B. divergens, is a medical emergency with lethality close to 50%, most cases of which are seen in splenectomized patients. The diagnosis requires the identification of the parasite on blood smears (Giemsa). Its morphology is different from that of Plasmodium, but the parasites can be mis-identified, as was the case for the first patient with human babesiosis reported in Switzerland, probably imported from Wales. For clinicians early identification of this disease, which may require renal dialysis and exchange transfusion is essential. The treatment of choice is clindamycin and quinine. PMID- 7770751 TI - Cryptosporidia--who is at risk? AB - Cryptosporidium parvum is a coccidian parasite originally described a century ago and, until recently, not considered to be a human pathogen. It has a complex life cycle, including both sexual and asexual reproduction, an auto-infectious cycle, and the ability to complete its development within a single host. The transmission form is a robust, environmentally resistant oocyst, excreted in the stool, which can exist for long periods of time in the environment. Because animals, in particular domesticated livestock, are its primary host, human infection is usually zoonotic. Oocysts often find their way into water supplies, and it resists chlorination and is incompletely filtered from processed drinking water supplies, even when filtration is working optimally. Transmission via ingestion of fecally contaminated swimming pool water, food, fomites, and sexual activities facilitating fecal-oral inoculation have been demonstrated. The major target of C. parvum in the host is the intestinal epithelial cell, resulting in diarrhea, sometimes profuse and persistent, although it may also infect other organs such as the gall bladder and lungs. Pathogenesis involves attachment, probably via a sporozoite lectin, invasion, probably involving apical organelles, replication within a parasitophorous vacuole with the host cell membrane, causing cellular dysfunction. Diagnosis is generally made by visualization of the oocyst form in stool by staining methods, the best of which appears to be auramine and fluorescence microscopy. Those at greatest risk are immunocompromised adults and children, especially those with AIDS, children in day care, travelers to endemic regions, dairy or cattle farm workers of their families or contacts, household contacts of cases or carriers, and possibly owners of infected dogs or cats or their neighbors. There is no specific therapy available, however in the immunocompetent host the illness is self-limited, lasting from a few days to 3 weeks, and long term carriage is uncommon. In the immunocompromised host, infection is prolonged, sometimes asymptomatic, but may result in chronic debilitating diarrhea with dehydration, malabsorption and wasting. Public health measures to reduce contamination of water supplies and vigilant surveillance will reduce the risk to populations. Reducing behaviors favoring fecal-oral transmission, such as certain sexual activities, and scrupulous hygiene in the day care setting would also reduce the likelihood of transmission but not eliminate it. Given our lack of knowledge about Cryptosporidium biology and pathogenesis, high priority should be given to research designed to increase our understanding of the organism and improve the chance of developing useful therapeutic or preventative drugs or strategies. PMID- 7770750 TI - [Cyst-forming Coccidia: Toxoplasma, Neospora, Sarcocystis]. AB - The most important cyst-forming coccidian parasites in human and veterinary medicine belong the genera of Toxoplasma, Neospora and Sarcocystis. Toxoplasma gondii shows its clinical relevance in congenital infections and opportunistic infections in immunodeficient patients. In veterinary medicine the parasite is predominantly the cause of important economic loss in livestock production. Neospora causes diseases resembling toxoplasmosis; neosporosis is one of the most important causes of bovine abortion in the US. Neospora caninum leads to myositis and paralysis in dogs. The potential implication of Neospora in toxoplasmosis like diseases in humans is not yet known. Sarcocystis is usually a relatively harmless intestinal parasite in humans. Recent data from tropical areas suggest that man can also become an intermediate host for certain Sarcocystis species, which potentially represents a source of opportunistic infection and disease in areas with increasing HIV prevalence. In veterinary medicine, Sarcocystis causes muscle diseases and also abortion or myeloencephalitis with lethal outcome in certain animal species. Molecular-epidemiological investigations have resulted in a new understanding of biological and population-genetic mechanisms relevant to the disease. Recently developed molecular techniques, such as transfection in protozoan parasites, are presently used not only to elucidate molecular pathogenetic events in the course of disease, but also to prepare potential new immuno-therapeutic tools for future vaccination against infection or disease. PMID- 7770753 TI - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). On porphyrinuria with acute ascending paralysis. 1919]. PMID- 7770752 TI - [New parasitic diseases in man: infections caused by Microsporida and Cyclospora species]. AB - The non-taxonomic term microsporidia relates to a group of organisms belonging to the order Microsporida of the phylum Microspora. Microsporidia are obligate intracellular spore-forming protozoa and have no metabolically active stages outside the host cell. Their host range is extensive and includes most invertebrates and all 5 classes of vertebrates. More than 100 microsporidial genera and almost 1000 species have now been identified. 5 genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora and Nosema) and unclassified microsporidia have been associated with human disease. Only 10 cases of microsporidiosis have been described among persons not infected with HIV. In contrast, microsporidia have gained increasing attention as important opportunistic pathogens in the evolving pandemic of HIV infection. Diagnosis depends on morphological demonstration of the organisms themselves. The potential sources and modes of transmission of human microsporidial infections are uncertain. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Preliminary observations of the possible utility of albendazole for infections due to Septata intestinalis and Encephalitozoon sp. have been reported. The success of therapy for intestinal Enterocytozoon bieneusi infection has been limited. Cyclospora sp. are recently described protozoa capable of causing diarrhea in immunocompetent and immunodeficient patients. Groups at risk for infection are children in the developing world, travellers and HIV-infected patients. Diagnosis depends on light-microscopic detection of oocysts in stool smears stained with acid-fast stains. Diarrhea is usually self-limiting. Diarrhea, however, may often last weeks to months, causing significant morbidity. Cotrimoxazole appears to be the drug of choice for treatment of Cyclospora infection. PMID- 7770754 TI - [Uncomplicated second pregnancy following acute fatty liver of pregnancy]. AB - Acute fatty liver is a rare but usually severe and frightening complication of the last trimester of pregnancy. Many patients therefore do not want or are warned against having another child. This report adds another case of successful consecutive pregnancy to the 28 documented cases in 24 patients. On the other hand, only 2 recurrences have been reported. Therefore, the wish for another pregnancy may be supported, provided the gravida is well informed and the necessary (bi)weekly clinical and laboratory checks are carried out in the last trimester (liver tests, uric acid, prothrombin time and, in case of doubt, further coagulation tests including antithrombin III). PMID- 7770756 TI - [Scientific raisins from 125 year SMW (Swiss Medical Weekly). "Parkinsonism" as sequela to encephalitis lethargica. 1916]. PMID- 7770757 TI - [Snoring--harmless or harmful?]. PMID- 7770755 TI - [Obstructive sleep apnea syndrome]. AB - This is an overview for the non-specialist of the pathophysiology, workup and treatment of the obstructive sleep apnea syndrome. The mechanisms leading to upper airway closure during sleep are discussed, as well as the current theoretical and experimental concepts for the apnea-induced arousal response and the consequent changes in sleep architecture and quality. Epidemiological data are summarized, with special reference to the problems of non-uniform definition criteria and examination techniques applied. In conclusion, a practical workup strategy and the current treatment options are summarized. PMID- 7770758 TI - [Screening for sleep apnea: clinical use of Mesam IV and Apnoe-Check]. AB - With the introduction of nasal continuous positive airway pressure as an effective treatment of the sleep apnea syndrome, the demand for costly polysomnographic investigations has markedly increased. Hence a reliable screening method would be desirable. Patients undergoing overnight oxymetry were simultaneously examined by MESAM (n = 54) and by Apnoe-Check (n = 23) in a prospective manner. The results were compared among themselves and with the complete overnight polysomnography (MESAM n = 38, Apnoe-Check n = 20). Simple overnight oxymetry, automatically assessed oxymetry by MESAM and apnea identification by Apnoe-Check correlated well with the polysomnographic findings. On the other hand, variation of heart rate, snoring events and changes of body position as identified by MESAM did not add relevant information. Only the detection of moderate to severe sleep apnea syndrome was satisfactory, though not infallible. Thus, there is still no screening method available to identify or exclude sleep apnea syndrome, particularly the milder form, which is nevertheless a significant disease. PMID- 7770759 TI - [Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors]. AB - In a retrospective study we analyzed the clinical and blood chemical data of 12 patients with severe tropical malaria in the intensive care units of the University Hospital Zurich and the Stadtspital Triemli, Zurich, between 1991 and 1994. None of the 12 patients had been exposed to malaria before or had taken drugs for chemoprophylaxis. 7 patients survived, 5 died from complications of malaria. According to the criteria of severe tropical malaria defined by the WHO, the following pathological clinical and blood chemical parameters were noted on admission: cerebral coma (2/12); blood hemoglobin < 5 g/dl (0/12), < 8 g/dl (2/12); serum creatinine > 265 mumol/l (3/12); blood glucose < 2.2 mmol/l (0.12); circulatory collapse/shock (0/12); bleeding/signs of disseminated intravascular coagulation in laboratory tests (4/12); acidosis with pH < 7.25 (1/12). Further signs of severe tropical malaria were: hyperparasitemia > 5% (9/12); qualitative and quantitative disturbances of consciousness (6/12); thrombocytopenia < 30 x 10(9)/l (9/12); hyponatremia 125-135 mmol/l (9/12), < 125 mmol/l (2/12); rhabdomyolysis with creatine kinase > 1000 U/l (4/12). The basic treatment consisted of parenteral quinine hydrochloride in all patients; doxycycline was added in 8 cases, clindamycin in 3. Adjuvant therapy with desferrioxamin was given in 3 cases. 6 patients had exchange transfusions. Parasitemia cleared in all patients within 5 to 6 days. Later in the course, 5 patients developed acute respiratory distress syndrome, 6 required hemofiltration due to oliguria, and one became comatose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770760 TI - [Incidence of insulin-dependent diabetes mellitus in Switzerland (1972-1993) in 19-year-old men]. AB - There is current debate whether prevalence of insulin-dependent diabetes mellitus is increasing in western countries. In Switzerland every male at age 19 years is legally obligated to appear before the Military Conscript Board, where health status is determined by physicians. We analyzed prevalence data concerning the diagnosis of diabetes mellitus in four full surveys (1972, 1982, 1987, 1993). The study included data from 162,607 Swiss males at age 19 years. Case numbers of birth cohorts and prevalence rates per 1000 are the following: [table: see text] Although the number of years surveyed is limited, trend analysis showed no evidence of an increase in the diabetes rates (total chi 2 = 4.953, DF = 3, 0.1 < p 0.2; chi 2 due to linear regression = 3.013, DF = 1, 0.05 < p < 0.1; chi 2 due to departure from linear regression = 1.940, DF = 2, 0.3 < p < 0.5). Overall cumulative incidence of diabetes mellitus was 1.30/1000 conscripts (95% confidence interval: 1.13-1.48/1000). We conclude that, in contrast to reports from other European countries, the cumulative incidence of insulin dependent diabetes mellitus has not increased among cohorts of Swiss males at age 19 years. PMID- 7770761 TI - [Protein antigens in case of asthma, rhinitis and dermatitis in patients occupationally exposed to flour]. AB - 21 patients gave sera to clarify their clinical hypersensitivity towards flour proteins. 6 had dermatitis, 3 rhinitis and the others asthma. 3 patients showed a control reactivity towards the electrophoretically separated flour protein antigens while others had antibodies to flour antigen with molecular weights less than 100 kD or 80 kD in the case of rye. Reactivity towards antigens with molecular weight higher than 50 kD was typical of dermatitis patients, while the rhinitis and asthma cases' sera reacted towards lighter flour proteins in the 20 30 kD range. The procedure is simple, a random serum sample (5 ml) suffices, and it allows demonstration of sensitization to flour protein in a way which may be helpful in the evaluation of exposure and the diagnosis of allergic conditions due to flour dust, a major etiology of occupational respiratory disease. PMID- 7770762 TI - [Scientific raisons from 125 years SMW (Swiss Medical Weekly). The active substances of ergot. 1921]. PMID- 7770763 TI - [Annual meeting of the Swiss Society of Pneumology. Fribourg, 6-7 April 1995. Abstracts]. PMID- 7770764 TI - Punctuated equilibrium in scientific publishing. PMID- 7770765 TI - High-frequency outer hair cell motility: corrections and addendum. PMID- 7770766 TI - Who owns the past? PMID- 7770767 TI - IL-12 at the crossroads. PMID- 7770768 TI - Origins of lichen fungi explored. PMID- 7770769 TI - Revisiting the fluid mosaic model of membranes. PMID- 7770770 TI - Evidence for a basalt-free surface on Mercury and implications for internal heat. AB - Microwave and mid-infrared observations reveal that Mercury's surface contains less FeO + TiO2 and at least as much feldspar as the lunar highlands. The results are compatible with the high albedo (brightness) of Mercury's surface at visible wavelengths in suggesting a rock and soil composition that is devoid of basalt, the primary differentiate of terrestrial mantles. The occurrence of a basalt free, highly differentiated crust is in accord with recent models of the planet's thermal evolution and suggests that Mercury has retained a hot interior as a result of a combination of inefficient mantle convection and minimal volcanic heat loss. PMID- 7770771 TI - Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. AB - In mice lacking the interleukin-2 receptor beta chain (IL-2R beta), T cells were shown to be spontaneously activated, resulting in exhaustive differentiation of B cells into plasma cells and the appearance of high serum concentrations of immunoglobulins G1 and E as well as autoantibodies that cause hemolytic anemia. Marked infiltrative granulocytopoiesis was also apparent, and the animals died after about 12 weeks. Depletion of CD4+ T cells in mutant mice rescued B cells without reversion of granulocyte abnormalities. T cells did not proliferate in response to polyclonal activators, nor could antigen-specific immune responses be elicited. Thus, IL-2R beta is required to keep the activation programs of T cells under control, to maintain homeostasis, and to prevent autoimmunity. PMID- 7770772 TI - Superresolution three-dimensional images of fluorescence in cells with minimal light exposure. AB - Fluorescent probes offer insight into the highly localized and rapid molecular events that underlie cell function. However, methods are required that can efficiently transform the limited signals from such probes into high-resolution images. An algorithm has now been developed that produces highly accurate images of fluorescent probe distribution inside cells with minimal light exposure and a conventional light microscope. This method provides resolution nearly four times greater than that currently available from any fluorescence microscope and was used to study several biological problems. PMID- 7770773 TI - Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage. AB - Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths. PMID- 7770774 TI - Crystal structure of a purple acid phosphatase containing a dinuclear Fe(III) Zn(II) active site. AB - Kidney bean purple acid phosphatase (KBPAP) is an Fe(III)-Zn(II) metalloenzyme resembling the mammalian Fe(III)-Fe(II) purple acid phosphatases. The structure of the homodimeric 111-kilodalton KBPAP was determined at a resolution of 2.9 angstroms. The enzyme contains two domains in each subunit. The active site is located in the carboxyl-terminal domain at the carboxy end of two sandwiched beta alpha beta alpha beta motifs. The two metal ions are 3.1 angstroms apart and bridged monodentately by Asp164. The iron is further coordinated by Tyr167, His325, and Asp135, and the zinc by His286, His323, and Asn201. The active-site structure is consistent with previous proposals regarding the mechanism of phosphate ester hydrolysis involving nucleophilic attack on the phosphate group by an Fe(III)-coordinated hydroxide ion. PMID- 7770775 TI - Multiple origins of lichen symbioses in fungi suggested by SSU rDNA phylogeny. AB - Phylogenetic hypotheses provide a context for examining the evolution of heterotrophic lifestyles. The lichen lifestyle, which is the symbiotic association of fungi with algae, is found in various representatives of Dicaryomycotina, both Ascomycetes and Basidiomycetes. A highly resolved parsimony analysis of small subunit ribosomal DNA (SSU rDNA) sequences suggests at least five independent origins of the lichen habit in disparate groups of Ascomycetes and Basidiomycetes. Because lichen associations arose from parasitic, mycorrhizal, or free-living saprobic fungi, neither mutualism nor parasitism should be construed as endpoints in symbiont evolution. PMID- 7770776 TI - Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. AB - The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance. PMID- 7770777 TI - Progesterone synthesis and myelin formation by Schwann cells. AB - Progesterone is shown here to be produced from pregnenolone by Schwann cells in peripheral nerves. After cryolesion of the sciatic nerve in male mice, axons regenerate and become myelinated. Blocking either the local synthesis or the receptor-mediated action of progesterone impaired remyelination. Administration of progesterone or its precursor, pregnenolone, to the lesion site increased the extent of myelin sheath formation. Myelination of axons was also increased when progesterone was added to cultures of rat dorsal root ganglia. These observations indicate a role for locally produced progesterone in myelination, demonstrate that progesterone is not simply a sex steroid, and suggest a new therapeutic approach to promote myelin repair. PMID- 7770778 TI - Reliability of spike timing in neocortical neurons. AB - It is not known whether the variability of neural activity in the cerebral cortex carries information or reflects noisy underlying mechanisms. In an examination of the reliability of spike generation using recordings from neurons in rat neocortical slices, the precision of spike timing was found to depend on stimulus transients. Constant stimuli led to imprecise spike trains, whereas stimuli with fluctuations resembling synaptic activity produced spike trains with timing reproducible to less than 1 millisecond. These data suggest a low intrinsic noise level in spike generation, which could allow cortical neurons to accurately transform synaptic input into spike sequences, supporting a possible role for spike timing in the processing of cortical information by the neocortex. PMID- 7770779 TI - Chemical characterization of a family of brain lipids that induce sleep. AB - A molecule isolated from the cerebrospinal fluid of sleep-deprived cats has been chemically characterized and identified as cis-9,10-octadecenoamide. Other fatty acid primary amides in addition to cis-9,10-octadecenoamide were identified as natural constituents of the cerebrospinal fluid of cat, rat, and human, indicating that these compounds compose a distinct family of brain lipids. Synthetic cis-9,10-octadecenoamide induced physiological sleep when injected into rats. Together, these results suggest that fatty acid primary amides may represent a previously unrecognized class of biological signaling molecules. PMID- 7770780 TI - Hyperthermia--its actual role in radiation oncology. Part III: Clinical rationale and results in deep seated tumors. AB - PURPOSE: Combined hyperthermia and radiation therapy has been reported to yield higher complete and durable responses than radiotherapy alone in superficial tumors. In deep seated tumors the effect of the combined treatment is still under research. METHODS: The literature and own clinical data are reviewed with regard to biological and physical fundamentals and clinical results. RESULTS: Clinical phase I to II studies have applied regional hyperthermia in the abdomen, the pelvic region and the extremities. Usually primary advanced, persistent or local recurrent and metastatic tumors were selected for treatment either due to poor response to conventional therapy or for effective palliation. The clinical data are presented concerning the following topics: invasive thermometry, temperature parameter in tumor and normal tissue, toxicity, tumor response, treatment planning, clinical trials and prognostic factors. Clinical results of thermoradiotherapy for advanced or recurrent rectal cancer, cervical cancer and soft tissue sarcomas are reviewed in detail. In addition, the prognostic relevance of temperature parameters and physiological conditions such as global tumor perfusion are discussed. CONCLUSION: Clinical issues of optimization of regional thermoradiotherapy are: improvement of hyperthermia technique, analysis of biological effects and mechanisms involved in temperature elevation, selection of appropriate study concepts for specific tumor sites. Part I has covered biological and technical fundamentals of clinical hyperthermia and has been published in Strahlenther. Onkol. 168 (1992), 183-190. Part II has covered clinical fundamentals and results in superficial tumors of clinical hyperthermia and has been published in Strahlenther. PMID- 7770781 TI - [Results of neutron therapy in recurrent malignant salivary gland tumors in the head and neck area]. AB - PURPOSE: The records of 33 patients of recurrent salivary gland tumors of the head and neck regions were analysed. PATIENTS AND METHODS: 33 patients with recurrent salivary gland tumors were treated with fast neutrons of a 14 MeV DT generator. All patients had been operated several times. 10 patients had been irradiated before with photons or electrons. 24 patients had macroscopic tumor. In many cases advanced tumors were treated. RESULTS: The median follow-up of our patients is 33 months. 6 patients are still alive without disease. 5 patients are alive with local recurrence or tumor progression. The calculated survival rate for all patients is 45% at 5 years. The calculated control rate for all patients is 43% at 5 years. Most of the late side effects according to the RTOG/EORTC score were moderate. Only in one case severe late side effects could be observed. CONCLUSION: According to the literature advanced recurrences of salivary gland tumors should be treated with fast neutrons. PMID- 7770782 TI - Radiographic changes following radiotherapy in the patients with lung cancer. Is the irradiated area of the mediastinum in the simulation film a significant factor? AB - BACKGROUND: Radiation induced lung injury is an ominous adverse reaction in the management of thoracic disease by radiation therapy. Although the importance of the area of irradiated lung is well known, the irradiated area of mediastinum is little to be considered in the routine treatment. PURPOSE: To evaluate the significance of the irradiated area of the mediastinum in the simulation film for radiation induced lung injury. PATIENTS AND METHODS: A total of 208 patients with primary lung cancer treated with radiation therapy were analyzed for incidence of radiation induced lung injury. Lung injury was defined as the appearance of an abnormal shadow on the chest radiograph. CT images were used to differentiate recurrence or other conditions. Age, sex, irradiation dose, irradiated lung area, T and N factors of the tumor, irradiated mediastinum area, performance status of patients, location of irradiated fields and use of chemotherapy were analyzed with Cox's multivariate regression model. RESULTS: The cumulative rate of radiation induced lung injury at 12 months was 85%. Significant factor of radiation induced lung injury was irradiated area of the mediastinum (p = 0.03). Irradiated area of the lung (p = 0.18, n.s.), total tumor dose (p = 0.1, n.s.), use of chemotherapy (p = 0.08, n.s.) and location of irradiated field (p = 0.08, n.s.) may also have an effect on radiation induced lung injury. CONCLUSION: The irradiated area of the mediastinum is one of the significant factors in radiation induced lung injury. PMID- 7770783 TI - [Value of SPECT-immunoscintigraphy in radiation treatment planning for patients with squamous cell carcinomas in the head and neck area]. AB - PURPOSE: Introduction of monoclonal antibodies (immunoscintigraphy) has significantly extended the diagnostic spectrum of nuclear medicine in oncology. The detection rate of this new method in patients bearing squamous cell carcinoma of head and neck is better compared to computed tomography and magnetic resonance imaging. In a prospective study, we examined whether immunoscintigraphy in addition to other imaging procedures is able to provide additional diagnostic information for radiation treatment planning. PMID- 7770784 TI - [Usefulness of prophylactic whole brain irradiation in small-cell bronchial carcinoma]. AB - PURPOSE: An analysis of the incidence of brain metastases in small cell lung cancer, time of occurring during the course of disease, and the prognosis of these patients depending on the use of prophylactic cranial irradiation for three well defined patient groups. MATERIAL AND METHODS: A retrospective study included 133 unselected patients with histologically proven SCLC who were treated from 1985-1990 in our department. From these, 118 patients without CNS metastases at primary diagnosis were divided into three well defined patient groups: group I consisted of 23 patients who achieved a complete remission after primary therapy and who were subsequently treated with PCI, group II consisted of 23 patients in complete remission without PCI. Group III consisted of 72 patients without CNS metastases at the primary diagnosis and without PCI treatment since they did not achieve a complete response after primary therapy. The primary therapy consisted of combined radiochemotherapy or only chemotherapy. Sixteen patients were treated only by irradiation. RESULTS: The overall incidence of CNS metastases for all 133 patients was 33.1%. The incidence of new CNS metastases in group I was 21.7% in group II 26.1%, and in group III 22.2%. The average time to development of CNS metastases after primary diagnosis was different for the three groups: in group I 15.4 months, in group II 9.5 months and in group III 8.4 months. No statistical significance was noted. Median survival time for group I was 16.1 months, for group II 13.8 months and 8.4 months for the group III. No statistical significance was achieved between group I and II (P > 0.05). CONCLUSIONS: These data suggest that treatment with PCI appears to be ineffective in reducing the incidence of subsequently CNS metastases or to improve survival of SCLC patients. We recommend the use of PCI only in well defined clinical studies. PMID- 7770786 TI - [Intraspinal metastasis of stage I anaplastic Wilms tumor]. AB - PURPOSE: Intraspinal metastasis of Wilms' tumors is a rare event with only 6 cases documented in the literature. PATIENT AND METHODS: We report a case of an intraspinal metastasis by a young child with anaplastic Wilms' tumor (stage I). A 9-year-old girl developed 8 months following nephrectomy and pre-operative chemotherapy strong back pain. Within 2 weeks signs of beginning of spinal cord compression were obtained. The magnetic resonance imaging showed a spinal cord compression with an intraspinal tumor mass Th 8 to 10. RESULTS: The child underwent immediate spinal cord decompression followed by chemotherapy and an additional radiotherapy of the metastatic region up to 30 Gy with most of neurologic recovery within 6 weeks. CONCLUSIONS: The case illustrates the importance of rapidly responding neurologic complications in patients with Wilms' tumor, even in stage I. PMID- 7770785 TI - Long-term survival after brain metastases in breast cancer. AB - PURPOSE: Long-term survival after whole brain irradiation for cerebral metastases is rare. In order to identify a possible subgroup of patients with a prolonged survival time, a retrospective analysis was carried out. PATIENTS AND METHODS: From 1977 to 1991, 197 patients with singular (51%) or multiple (49%) brain metastases were treated with whole brain irradiation (30 to 36 Gy, 2 to 3 Gy daily fractions, an additional boost of 8 to 20 Gy in 8%) or resection of a singular metastasis and postoperative irradiation (36 patients, 30 to 36 Gy, 2 to 3 Gy fractions whole brain irradiation, boost of 8 to 20 Gy in 31%). RESULTS: Fifty-seven patients (24%) had metastases of breast cancer. In this group, 3 of 8 patients with combined treatment of a singular metastasis survived more than 5 years from the onset of brain irradiation, compared to 1 of 8 patients with non small-cell lung cancer and none of 14 patients with unknown primaries. In the group which was treated with irradiation only, breast cancer patients with an interval of more than 5 years between primary and brain metastasis had the best prognosis with 4 of 12 patients surviving more than 3 years, but less than 5 years. CONCLUSION: These results demonstrate that long-term survival is not only possible in the known cases of solitary brain metastasis in non-small-cell lung cancer but also in breast cancer, combined treatment provided. PMID- 7770787 TI - [Hyperfractionated irradiation in bladder carcinoma]. PMID- 7770788 TI - [Survival of children with primitive neuroectodermal tumors and malignant ependymomas of the central nervous system after treatment with 8 cytostatic agents in one day. A report of the Children's Cancer Group]. PMID- 7770789 TI - [Minimal lymphatic tumor cell dissemination as a prognostic factor in non-small cell lung carcinoma]. PMID- 7770790 TI - [Role of radiotherapy in the framework of curative chemotherapy concept in local advanced non-small-cell bronchial carcinoma]. PMID- 7770791 TI - [In reference to the article by Dahl et al: Do acute side effects during radiotherapy predict tumour response in rectal carcinoma? Acta Oncol. 33 (1994), 409-413, and to Commented Literature by J. Dunst: Acute side effects and therapeutic success in preoperative radiotherapy of rectal carcinoma. Strahlenther. Onkol. 171 (1995), issue 1, 54-55]. PMID- 7770792 TI - [Pulmonary ventilation function in middle-aged and elderly patients with chronic bronchitis]. AB - The indices of lung ventilation and biomechanics of breathing were determined in 48 patients with chronic obstructive bronchitis (COB) aged 60-79 and 45 healthy subjects of the same age. Inpatients with COB a rise of lung ventilation, work of breathing, ventilation equivalent, positive reaction to oxygen, a decrease of maximal breathing capacity and reserve of breathing take place that reflect excessive and uneffective ventilation, limitation of its functional performance. These specific features are due to an increase in the total lung capacity at the expense of residual volume against a decrease of vital capacity with diminution of alveolar ventilation to lung ventilation ratio. But of decisive significance was disturbance of bronchial patency manifesting in a decrease of Tiffeneau index, midexpiratory flow, respiratory flows in forced respiration, especially in expiratory phase, concavity of flow-volume curve to volume axis, a rise of bronchial resistance. PMID- 7770793 TI - [The cholesterol esterase activity of the blood monocytes and alveolar macrophages in patients with chronic bronchitis]. AB - The activity of cholesterol esterase (CE) in blood monocytes and alveolar macrophages (AMF) of bronchoalveolar fluid (BAF) according to Brecher et al., cell composition of endobronchial cytogram were investigated in 32 patients with chronic bronchitis (CB) and control subjects. In CB sufferers CE activity in AMF was inhibited, while in monocytes it was elevated reaching maximal values in purulent bronchopulmonary CB. Determination of CE activity in AMF and peripheral blood monocytes in CB may serve an additional diagnostic indicator of impaired lipid metabolism and suggests new approaches to investigation of CB pathogenesis. PMID- 7770794 TI - [The dynamic indices of external respiratory function in patients with chronic obstructive bronchitis during the course of the work week under manufacturing conditions]. PMID- 7770795 TI - [A trial of the use of the new Russian preparation oxymetacil in patients with chronic nonspecific lung diseases]. AB - The trial of oxymethacyl was conducted in 20 CNSPD patients. Clinicoimmunological examinations provided evidence on the drug effectiveness as it stimulated cell immunity, phagocytosis, was well tolerated, caused no side effects. The highest response was achieved in combination of oxymethacyl with antibacterial therapy. Normalization of clinical and immunological indices in CNPD patients suggests immunocorrective effect of oxymethacyl. PMID- 7770796 TI - [Changes in the sensitivity of leukocytes to the inhibiting effect of CO2 on their generation of active forms of oxygen in bronchial asthma patients]. AB - 30 bronchial asthma (BA) patients and 15 donors were exposed to 8.3% and 20.8% CO2 to bring out leukocytes sensitivity to CO2 by generation of active oxygen (AO) in bronchial asthma. CO2 effects on leukocyte AO generation were defined by luminol-dependent chemiluminescence (CL) before and after the exposure to CO2. It was found that in healthy subjects 8.3% and 20.8% CO2 noticeably inhibits leukocyte CL. However, in 70% of asthmatics with BA exacerbation leukocyte sensitivity to CO2 inhibition diminished. This was normal in 30% of BA patients. With BA aggravation, leukocyte sensitivity to CO2 tended to a decrease. Remission brought a complete or partial recovery of the above sensitivity. Thus, on the one hand, CO2 is involved in BA pathogenesis in terms of its inhibitory effect on AO generation by leukocytes; on the other hand, only in 30% of BA patients high CO2 concentrations as a treatment may be justified. PMID- 7770797 TI - [A comparative study of the expression of activation markers on T-lymphocyte subpopulations in different forms of bronchial asthma]. AB - In this study we investigated a phenotype of intact and PHA-stimulated T lymphocytes from peripheral blood of patients with allergic and nonallergic asthma. Expression of the activation markers (CD25, CD71, HLA-DR) on subsets of T lymphocytes (CD4+ and CD8+) was determined using double-colour flow cytometry. It was found that nonallergic patients had increased percentages of CD4+CD25+, CD8+CD25+, CD4+HLA-DR+, CD8+HLA-DR+ cells. Allergic patients had a significant increase of CD4+CD25+ cells only. To examine functional significance of these changes mononuclear cells were cultivated with PHA in vitro. Thus, our findings improve our knowledge about asthma pathogenesis and create the grounds for pathogenetically validated immunocorrection. PMID- 7770798 TI - [An analysis of the data from the neurophysiological examination of patients with bronchial asthma and hyperventilation]. AB - Bronchial asthma (BA) patients with hyperventilation (HV) were examined by means of evoked cutaneous sympathetic potential (ECSP) and short-latency evoked stem potentials to acoustic stimulation (SLESP to AS). Measurements of these parameters allowed quantitation and differentiation of hyperventilation disorders in BA patients. The latter were divided into 4 groups: BA patients with HV syndrome (HVS), BA patients with functional HV (FHV), BA patients with spontaneous HV (SHV) and BA patients without HV. BA patients with HVS exhibited a significant increase of latent ECSP period and latent periods III and V SLESP to AS peaks. This evidences for vegetative neuropathy and dysfunction of the pons and mesencephalic brain compartments. In BA patients with FHV there was a longer latent period II of SLESP to AS peak indicating dysfunction of caudal brain stem. BA patients with SHV and without HV had no significant shifts. PMID- 7770799 TI - [Pneumonia--a topical problem of medicine]. PMID- 7770800 TI - [The therapeutic potentials of Ditec in bronchial asthma patients]. AB - Ditec effects on clinicofunctional status were investigated in 15 patients with mild and moderate atopic bronchial asthma (ABA) aged 20-50 (5 males and 10 females). A single ditec dose had a broncholytic effect along the entire bronchial tree and reduced sensitivity to acetylcholine. Magnesium sulfate (a single dose 3 mmol Mg2+, pH 6.6, the solution osmolality 260 mmol/l) potentiated ditec action on nonspecific hyperreactivity of the bronchial tree. Four-week ditec course induced no considerable changes in bronchial permeability, but increased reversibility of bronchial obstruction, inhibited sensitivity and response of the bronchial tree to acetylcholine. Course administration of ditec lowered endobronchial concentration of histamine and lipid peroxidation intensity showing antiallergic and antiinflammatory properties of the drug. Ditec is recommended for ABA and other asthma forms treatment as a safe and effective modality. PMID- 7770801 TI - [Beclomethasone dipropionate, budesonide and flunisolide in the treatment of bronchial asthma (a review of the literature and the authors' own research)]. AB - Inhalation corticosteroids (beclometasone dipropionate, budesonide, flunisolide) proved effective against bronchial asthma (BA) and safe as they induce no severe systemic side effects. Of these three drugs side effects arise most frequently in administration of beclometasone dipropionate, least frequently of flunisolide. These inhalation corticosteroids are indicated both in non-steroid-dependent and steroid-dependent BA to reduce the dose of oral steroids or, if possible, for their complete discontinuation. Flunisolide is the most potent and effective of all inhalation corticosteroids used in current practice. PMID- 7770802 TI - The morphological properties of the blood thrombocytes in bronchial asthma patients before and after thrombocytapheresis. AB - Morphological characteristics of platelets were assessed electron microscopically in 15 patients with atopic and aspirin bronchial asthma (BA) before and after thrombocytapheresis (TA). All the patients had a definite shift of platelet subpopulations to greater percentage of spherical forms as well as defects in cell ultrastructure. This makes evident platelet activation in patients with BA aggravation. TA entails a positive trend to normalization of platelet subpopulations and cytoskeleton. The ability to normalize platelet morphofunctional status determines its clinical effectiveness in bronchial asthma. PMID- 7770804 TI - [A comparative assessment of the effect of different methods of glucocorticosteroid therapy on the hypophyseal-adrenal system in bronchial asthma patients]. AB - As shown by morphofunctional examinations of hypophyseal-adrenal system in 137 BA patients and post mortem examinations of adrenal cortex in 72 BA cases, most pronounced defects in glucocorticosteroid (GCS) biosynthesis and metabolism were recorded in patients on long-term GCS regiments (5-10 years and more). They displayed low levels of 11-OCS and 17-OCS, enhanced transcortin binding capacity, diminished adrenocortical reserves. Beclometasone propionate, endobronchial liposomes with hydrocortisone had no negative adrenal effects. PMID- 7770803 TI - [The function of the hypothalamo-hypophyseal-gonadal system in patients with bronchial asthma without and in combination with arterial hypertension]. AB - In the origin of arterial hypertension in bronchial asthma a significant role is played by the involvement of the lungs in metabolism of steroid hormones. Hypothalamo-hypophyseal-gonadal system was studied in 39 females suffering from bronchial asthma alone and in 47 asthmatic females suffering from bronchial asthma alone and in 47 asthmatic females with arterial hypertension. As indicated by radioimmunoassay, the impaired feedback between hypothalamo-hypophyseal and sexual functions may be responsible for stabilization of arterial hypertension in bronchial asthma. PMID- 7770805 TI - [The diastolic function of the right and left heart ventricles in patients with primary pulmonary hypertension]. AB - To evaluate the condition of left and right ventricular functions in patients with primary pulmonary hypertension (PPH) 21 patients (13 females and 8 males, mean age 35.4 +/- 10.0) were examined. The patients were ill for 5.7 +/- 3.5 years. Ventricular filling was characterized basing on computer data of transmitral and transtricuspid diastolic flow obtained at doppler echocardiography. Right ventricular function proved impaired in all the examinees: early in the disease the speed of early filling (Ve) was inhibited, while late filling was enhanced (Va). At terminal stages of the disease Ve increased, but Va reduced. Left ventricular function was also involved in all the patients: low Ve with the disease progression became more and more evident. PMID- 7770806 TI - [The current status of the problem of the surfactant system of the lungs]. PMID- 7770807 TI - [The basic trends in the research on and treatment of chronic obstructive lung diseases. The Working Group of the Canadian Thoracic Society]. PMID- 7770808 TI - [The diagnosis and treatment of tuberculosis of the respiratory organs]. PMID- 7770809 TI - [The use of specific bronchial provocation tests in the diagnosis of atopic bronchial asthma]. PMID- 7770810 TI - [A case of leiomyomatosis with a clinical picture of chylopericardium and chylothorax]. PMID- 7770812 TI - [[One needs certain experience--and quality control. Interview with Prof. D.J. Vonderschmitt. Interview by K. Reinhardt]. PMID- 7770811 TI - [Rovamycin (spiramycin)--a macrolide antibiotic for intravenous administration: a trial in the treatment of pneumonia]. AB - An open non-comparative study of rovamycin (spiramycin produced by Rhone-Poulenc Rorer) for intravenous administration was performed to evaluate its clinical and bacteriological efficacy, safety and tolerance. Thirty patients (adults aged 16 65 years) with community-acquired pneumonia were involved into the study. Two patients were dropped out because of adverse events. Dosage regimen was 1,500,000 I.U. three times a day (intravenous infusion). The treatment was continued after partial recovery (3,000,000 I.U. per os). Spiramycin showed a high clinical efficacy. Approximately half of the patients (41.4-55.6%) had positive clinical trends by third day of spiramycin treatment. The overall clinical efficacy by the completion of the drug administration reached 90.0%. Bacteriological activity was observed in 93.4% of the patients treated. Adverse events were observed in 6 (20.0%) patients, including 2 dropouts. Serious side effects were not registered. As rovamycin showed high clinical efficacy and good safety the drug may be recommended for the treatment of adult pneumonia. PMID- 7770813 TI - [50 years of clinical chemistry, first hand experience]. AB - Approximately since 1945, progress in the field of photometric analysis also found its way into the laboratories of clinical chemistry. These techniques almost completely replaced the then prevailing gravimetric and titrimetric methods. At the same epoch, many of the biochemical reagents which up to then had to be prepared by the clinical laboratories themselves with great expenditure of work became commercially available. The increasing number of analytical orders could only be mastered thanks to the newly developed analyzers. Novel microliter techniques made it possible to diminish drastically the volumes of samples and reagents necessary. The radioimmunoassay opened up new analytical dimensions, the limits of detection and of quantification were expanded downwards to the picomol range. Soon afterwards, enzymes and/or fluorochromes were used as markers in immunoassays. The development of monoclonal antibodies constituted further important progress in this field. The latest revolutionary invention is doubtlessly the polymerase chain reaction (PCR), and related techniques. These methods are bound to bring about fundamental change not only in clinical chemistry but in the medical laboratory diagnostics in general. PMID- 7770814 TI - [Interpretation of numerical laboratory values]. AB - Numerical values for laboratory tests ae usually divided into positive and negative results by a discriminating value. This raises the question of the reliability of the results, i.e. the probability of the presence of the tested disorder, if the result is positive. The present paper shows that this probability depends on the sensitivity and the specificity of the test as well as on the prevalence of the disorder in the population of patients under investigation. The usual reference values for laboratory tests turns out to be highly specific. The predictive value of a test result can be considerably improved by limiting the diagnostic possibilities. Tests with insufficient sensitivity and specificity are not applicable in screening for disorders or diseases. PMID- 7770815 TI - [Quality control in the physician's laboratory]. AB - All measures in quality assurance, including quality control, aim at minimizing and detecting errors in the clinical laboratory. Quality control is performed by using internal quality control material and by participating in external quality assessment schemes. These measures for quality assurance are an essential part of the new index of clinical tests, issued by the federal department for internal affairs on 1 January 1994. An agreement has been signed by the representatives of the associations performing laboratory analyses (hospitals, physicians, private laboratories) and by the health insurances, saying that internal as well as external quality control will be mandatory in Switzerland beginning 1 July 1995. The FMH is now asked to supply the health insurances with a list of physicians performing laboratory analyses until 1 July. For physicians who will not have registered neither with the respective professional organization nor one of the health care insurances by July 1995, the reimbursements will be reduced. PMID- 7770816 TI - [Influence factors in the physician's laboratory]. AB - Preanalytical influence factors are of paramount significance for the quality of a laboratory result. As a rule, their importance is greater than the inadequacies of the analytical process. Examples from the physician's laboratory concerning adult patients and primary samples are discussed. Weak points can be a lack of professionalism in the personnel involved as well as the need to send out and transport samples. The strong point of the office laboratory is its orientation towards a specific patient. PMID- 7770817 TI - [Urine analysis in the physician's laboratory]. AB - The practitioner who wants to perform urinalysis by means of rapid tests either in his office or at the bedside is informed of the available possibilities. Directives for the choice of appropriate reagents and for their interpretation are presented. PMID- 7770818 TI - [Nephrological basis diagnosis in clinical practice]. AB - The traditional urinalysis program, consisting of qualitative tests and the microscopical analysis of the urinary sediment, does no longer seem to be an adequate strategy to meet current medical quality requirements. New sensitive tests allow to exclude dysfunctions of glomerular and tubular function with hitherto unknown efficiency. This is possible by application of simple assays based on immunological techniques for albumin and alpha-1-microglobulin, which can be used in any medical office without technical equipment. Any finding of proteinuria, haematuria or leukocyturia may be differentiated by simple turbidimetric and microscopic procedures to separate renal from prerenal and postrenal causes. The new techniques have been successfully applied in early detection of renal complications in diabetics and hypertonics as well as immunological forms of renal disease. It is to be expected that the broader application of the new strategy helps to reduce many invasive investigations for the benefit of patients. PMID- 7770819 TI - [The hematological laboratory of clinical practice]. AB - The spectrum of analyses of a hematological laboratory comprises the counts of erythrocytes, leukocytes and platelets, the determinations of the hemoglobin concentration and of the hematocrit, the calculation of the red cell indices and the microscopic examination of the blood film. The determination of white blood cells, platelets, hematocrit and MCV as well as staining of the blood film should be performed within two hours after blood sampling. The hemoglobin concentration, red-cell count and MCH value remain constant for five days, provided that the blood samples is stored at 4 degrees C. The recognition of morphologically 'minor' pathological findings is important in view of the possible clinical significance that they might have. In the case of thrombotic-thrombocytopenic purpura, for instance, it is very important that the fragmentocytes are recognized and recorded. The grading of pathological findings by use of +, ++, is based on strict limits of ranges. Quality control and quality assurance are integral parts of the daily laboratory performance; moreover, the importance of external quality control in morphological hematology is stressed as being a challenge to the hematological laboratory technologist. PMID- 7770820 TI - [Lipid status in the physician's laboratory]. AB - Lipid analysis should be tailored to the likelihood of hyperlipidemia and atherosclerosis. In healthy individuals without a family history of hyperlipidemia, it is sufficient to obtain readings of total cholesterol and high density lipoprotein (HDL) cholesterol. In patients with a family history of hyperlipidemia, in addition, triglycerides should be measured. In patients with manifest atherosclerotic disease, the lipid profile should always include plasma cholesterol and triglycerides as well as HDL cholesterol; if these do not explain presence or extent of atherosclerosis, apolipoprotein (a) should be measured. Patients with diabetes mellitus should undergo the same diagnostic work-up as those with atherosclerotic disease. An apolipoprotein B reading (together with triglyceride levels) is sometimes helpful in patients with diabetes mellitus, allowing to estimate the size of triglyceride-rich lipoproteins. In patients with pancreatitis, longitudinal assessment of plasma triglycerides and, if available, measurement of HDL triglyceride are useful to unmask underlying hyperlipidemia. PMID- 7770821 TI - [Monitoring of coagulation status in the physician's laboratory]. AB - The usual coagulation tests performed in the medical practitioner's office are the prothrombin time (PT) and, less frequently, the activated partial thromboplastin time (aPTT, PTT), PT and aPTT are used as screening tests for coagulation disorders and for the monitoring of oral anticoagulation or home treatment with unfractionated heparin, respectively. Considered a 'simple test', the PT requires important conditions to be fulfilled by the laboratory. The results expressed in seconds, as a ratio, as PT-index and in activity percentages depend on the PT method and its local adaptation. The only way to communicate the intensity of oral anticoagulation to other doctors, hospitals and countries is to convert the PT seconds into international normalized ratios (INR). This requires the determination of the mean normal prothrombin time by each laboratory and the knowledge of the appropriate international sensitivity index (ISI). Reference curves are needed for PT expression as activity percentages. The PT of capillary blood deserves special consideration. Test performance is guided by regular internal and external quality control procedures. PMID- 7770822 TI - [C-reactive protein or blood sedimentation reaction os preventive studies in the physician's laboratory?]. AB - The laboratory examinations are more and more significant in the practical internal medicine. The results are basic for decision-making in medicine. The patients are asking for check-up examinations, including screening examinations in the laboratory. We try to compare the significance of two important laboratory tests. The C-reactive protein (CRP) is very sensitive and allows a graduation of the inflammatory reaction. It is useful to take the CRP in a valuable screening examination. Compared with the erythrocyte sedimentation rate (ESR), an elevated CRP always signifies an organic illness. A normal ESR has a poor predictive value. An elevated ESR supports only the history and the clinical findings of a suspected diagnoses. There is no possibility to screen patients without symptoms by ESR. We use ESR to follow-up diseases like arteritis temporalis and polymyalgia rheumatica and to measure the therapeutic effect. PMID- 7770823 TI - [Microbiological diagnosis in the clinical laboratory]. AB - In general, microbiological diagnostic procedures in the practitioner's office are limited to direct detection of group A streptococci in throat swabs in patients with pharyngitis and to semiquantitative urine culture with Uricult or Urotube test kits in patients in whom urinary tract infection is suspected. Negative direct tests with throat swabs should be confirmed by culture in the clinical microbiology laboratory, as several test kits have only moderate sensitivity in detecting group-A beta-hemolytic streptococci and do not detect other groups of beta-hemolytic streptococci. The results of semiquantitative urine cultures should always be interpreted together with clinical data. Quality control procedures are necessary for the accurate performance of these tests, and an external quality assessment program will probably be introduced in the near future. PMID- 7770824 TI - [A memorandum at a milestone--memories, wormwood and joint responsibility]. PMID- 7770825 TI - [Treatment of acute respiratory failure]. PMID- 7770826 TI - [Not all people live in the same community--obligation to report infectious diseases]. PMID- 7770827 TI - [Evaluation of the National Notification System for infectious diseases during an outbreak of Shigella epidemic in Norway 1994]. AB - The National Notification System for Infectious Diseases, in Norwegian abbreviated to MSIS, registered 110 cases of Shigella sonnei-infection in persons with debut of symptoms during weeks 21 to 25, 1994, and where we did not receive information that the patients had been abroad. We evaluated the notification system during this outbreak of infectious disease by looking at delays in the notification process and estimating the proportion of patients who received an etiological diagnosis. It took a median time of seven days from onset of illness until a faecal specimen was obtained and a further ten days (maximum 15 days) until the result was registered in MSIS. The time lapse between receiving the specimen until MSIS had registered the result varied from six to 15 days among the laboratories which sent more than four notifications. In the summarical notification system we registered an increase of 712 cases (86%) of acute gastroenteritis compared with the same week the previous two years. PMID- 7770828 TI - [Use of a mask as an alternative to endotracheal intubation in acute respiratory failure]. AB - Acute respiratory failure that is unresponsive to medical treatment requires ventilatory support. Non-invasive treatment with a nose or face mask is an alternative to endotracheal intubation in awake and cooperative patients. In patients with acute cardiogenic pulmonary oedema the application of continuous positive airway pressure (CPAP) increases cardiac output. CPAP-treatment is also effective in acute hypercapnic respiratory failure and oxygenation difficulties, but in these conditions pressure or volume-cycled positive pressure ventilation with a mask as an interface often has more to offer. The method reduces the need for endotracheal intubation and hence the time spent by the patient in the intensive care unit, but the need for personnel resources is equal. Possible clinical problems are skin erosions on the bridge of the nose due to pressure from the mask, and systemic hypotension. PMID- 7770829 TI - [Multiple sclerosis and prerequisites for driver's licence. A retrospective study of 33 patients with multiple sclerosis assessed at Sunnaas hospital]. AB - There is increasing interest in assessing the prerequisites for a driver's licence among patients with traumatic brain injury, cerebrovascular accidents and other diseases of the central nervous system which cause cognitive impairments. In the present study, 33 patients with multiple sclerosis, 20 females and 13 males of mean age 43 years, were medically and neuropsychologically examined, and some were assessed in a practical driving test. In total, 19 patients were allowed to drive and 14 were refused. Regression analysis showed that, when deciding for or against driving, cognitive and emotional deficits were given more weight than duration of illness and degree of neurologic deficit. The authors discuss guidelines for assessing the prerequisites for a driver's licence among patients with multiple sclerosis, and indicators for when assessment is warranted. PMID- 7770830 TI - [Bismuth. An old medicine of current interest]. AB - Bismuth has been used to treat dyspepsia for more than a hundred years, and has now become an important element in the treatment of peptic ulcer disease. Less than 1% of ingested bismuth is absorbed in the gastrointestinal tract and is excreted in the urine. Bismuth forms a protective coating on the mucosa, it stimulates secretion of bicarbonate and has an effect on the G-cell and Helicobacter pylori. Bismuth gives equal ulcer healing rates as H2-receptor blocking agents, but causes significantly less relapses. Triple treatment with bismuth, tetracycline and metronidazole eradicates H pylori in 95% of patients. Bismuth accumulates in the body during treatment and is neurotoxic, and it cannot be excluded that even short-term treatment may cause subclinical damage to the central nervous system. PMID- 7770831 TI - [Diet and lipid status in pregnant women]. AB - Pregnancy increases the requirement for nutrients and changes the metabolism of lipids and other compounds. We investigated the dietary composition and followed the changes in serum lipids during pregnancy among 20 women age 25-36 years. The women's diet was stable during pregnancy, but the intake of vitamin D, iron and fibre was lower than the national recommendations. Fat provided about 31% of the energy, saturated fat 12%. The total cholesterol concentration rose from 4.4 (95% confidence interval 4.2-4.6) to 7.0 mmol/l (6.5-7.5) (p < 0.0001) without changes in dietary composition. Even in this group of health-conscious, pregnant women the diet did not meet the national dietary recommendations. In addition, the composition of the fat in the diet was unfavourable. Optimal follow-up of pregnant women should include dietary counselling. PMID- 7770832 TI - [Clostridium difficile infection. The nosocomial aspect]. AB - Clostridium difficile infection is discussed relatively rarely as a nosocomial problem in Norway. Epidemiological studies have shown Clostridium difficile diarrhoea to be frequently an antibiotica-associated nosocomial disease. We describe a material consisting of 22 patients with Clostridium difficile infection from a county hospital in Norway. The inclusion criteria were a clinical disease with diarrhoea and a positive test for Clostridium difficile toxin A and/or B in the faeces. 11 patients were or had been hospitalized for a short period in one specific medical ward when diagnosed. These and five other patients probably had a hospital-acquired Clostridium difficile infection. We discuss the nosocomial aspect and the clinical characteristics of the disease in our material. PMID- 7770833 TI - [Surgical treatment of symptomatic pancreas divisum]. AB - Pancreas divisum is found in 5% of the population. It is linked to three clinical entities; recurrent epigastric pain, and acute and chronic pancreatitis. The relation between chronic pancreatitis and pancreas divisum is, however, uncertain. Pancreas divisum is controversial as a cause of acute pancreatitis and abdominal pain. However, this association probably exists as surgical sphincteroplasty of the minor papilla alleviate symptoms in a high proportion of patients. We have treated two patients surgically. Patient 1 was hospitalized 11 times because of recurrent acute pancreatitis. Two and a half years after sphincteroplasty he has had no further attacks of abdominal pain. Patient 2 had had recurrent epigastric pain, mostly related to meals, since early childhood. Secretin stimulation initially showed normal pancreatic duct dilatation and emptying. After sphincteroplasty, and reoperation for stricture, she can eat normally without pain one year after the last operation. We conclude that in selected patients surgical treatment of symptomatic pancreas divisum is beneficial. Sphincteroplasty should be considered as treatment in patients with pancreas divisum and recurrent acute pancreatitis or pain, as long as other causes are excluded. PMID- 7770835 TI - [Learning and memory]. AB - The ability to learn and to remember increases the adaptability of organisms. The article contains a brief survey of different types of learning and memory and of brain areas of particular importance for these functions. The lessons learnt from patient HM and a personal account of his appearance are given. Finally selected cellular and molecular models for learning and memory in lower and higher animals are briefly reviewed. PMID- 7770834 TI - [Clinical examination in general practice--a consulatation. Experiences after the first examination]. AB - In 1994 the first examination in general practice was arranged for graduate students at the medical school in Bergen. The examination consisted of a written part, and an oral, clinical examination. We report some experiences and reflections concerning the latter. Patients with commonly occurring health disorders were recruited from the practices of internal and external examiners. The performance of the student was assessed according to the skills in respect of clinical issues, communication, consultation tasks, and theoretical matters. The correspondence between the assessment of different examinators was very good, and the marks were well distributed. The students' evaluation and our own experiences lead to the conclusion that this kind of examination seems to be suitable for differentiated testing of skills and knowledge in general practice. PMID- 7770836 TI - [Language disorders]. AB - Language is the basis for acquisition and execution of communicative skills. The neurological structures underlying language can be localized through clinical pathological studies and neuroimaging studies. The classical language areas (Broca and Wernicke areas) are involved in lesions causing aphasia, and the main types of aphasia are motor (Broca), sensory (Wernicke), global and anomic aphasia. In stable lesions a negatively accelerated recovery curve is observed. Age and severity of aphasia are important prognostic factors. Treatment consists of broadly targeted language stimulation, but specialists services are important for assessment, education, and selection of patients for special forms of therapy. PMID- 7770837 TI - [Norwegian front fighters 1940-1945, 50 years later. Experiences, strains, medical and social conditions]. AB - The author describes a medical and social investigation of 181 Norwegian war veterans who served on the Eastern Front during World War II. To ensure representativity, special emphasis is placed on 76 Norwegians in 1st Company, Regiment Norge, as listed in January 1944. They have been interviewed about hardships during war service in the civil war in Spain and until spring 1945, during captivity in Russia, in other Allied forces' camps and in Norwegian camps and prisons after the war. Their medical and social status from 1940 until today has been studied. The "front fighters" are a heavily strained group. This is best illustrated by their death rates during the war and in the first years after the war. However, as a group, they have more resources than the general population, and have done comparatively well since the war, in spite of physical and social handicaps. PMID- 7770839 TI - [EDTA in the treatment of arteriosclerosis]. AB - EDTA has been used since the early fifties in the treatment of arteriosclerosis. There are few serious complications connected with using therapeutic doses of EDTA, although numerous side effects can arise. Several theories exist which suggest that the drug has a positive effect on atheromatous plaque; no such effect has been proven in vivo. Many papers claim to show the positive effect of EDTA on angina pectoris and intermittent claudication, but only one double blind placebo controlled experiment has been reported. In a sample of 153 claudicatio intermittens patients, no significant improvement in the distance walked nor in the ankle/brachial-index was proven, nor did the patients themselves notice any improvement. A professional investigation of the treatment, carried out by Norwegian Health Authority in 1981, concluded by advising Norwegian physicians not to recommend this kind of treatment for their patients. Since then, no clinical documentation of the effect of the treatment has become available. It must therefore be regarded as ethically unsound practice to start such treatment, unless as part of a clinically controlled experiment. PMID- 7770838 TI - [The Norwegian Medical Association under German control. Intrigues, the power game, the breakdown]. AB - Norway was occupied by the Germans from April-May 1940 until May 1945. As from September 1940, Hitler decided to establish a civilian administration in Norway with the help of the collaborating party "Nasjonal Samling" (NS). NS quickly tried to gain control over the professional organizations, with the aim of legalizing the NS administration in the eyes of the Germans. They met great resistance, also at the Norwegian Medical Association. The legal executive committee refused to cooperate with the NS leadership, and 85% of the members left the Association in 1941. A strong secret resistance movement began among the doctors, and the strongly curtailed NS-controlled Medical Association attained no political influence during the war, and was finally reduced to an appendix of the Ministry. PMID- 7770840 TI - [A political prisoner in Norway and Germany 1941-1945. Experiences of a medical student]. PMID- 7770841 TI - [SS physicians]. PMID- 7770842 TI - [Use of results of unethical research--will the use ethically legitimise this research?]. PMID- 7770843 TI - [Prevention is more difficult than treatment--and it is not easy to see its effect]. PMID- 7770844 TI - [Unreasonable PR-campaign of the Norwegian Radium Hospital on the treatment of basalioma]. PMID- 7770845 TI - [Smoking, risk and the Norwegians]. PMID- 7770846 TI - [When should patients be admitted to hospital?]. PMID- 7770847 TI - [Non-steroidal anti-inflammatory agents--are they used correctly?]. PMID- 7770848 TI - [Epilepsy service. From individual to special care]. PMID- 7770849 TI - [Children with asthma--does society respond to the challenge?]. PMID- 7770850 TI - [To how much strain are families with asthmatic children exposed?]. AB - Children with bronchial asthma may have coping problems which involve the whole family. The aim of this study was to find out what strain such families may experience. A questionnaire was sent to all children who, during a five year period, were registered as having a diagnosis of bronchial obstruction in the Department of Paediatrics, Innherred Hospital, Norway. The parents of a sample of the children were interviewed, and the parents of 42 children also answered a questionnaire about coping problems and strain. The results showed that the prevalence of coping problems and strain was low for these families at the time of the interview. Coping problems were greater during the first two years after asthma debut. Mothers felt more strain than the fathers during the two first years. PMID- 7770851 TI - [Should older patients be admitted for coronary evaluation and treatment? With special emphasis on a survey and catheter-based revascularization of patients over 70 years of age]. AB - A three year survey of patients undergoing diagnostic left heart catheterization and PTCA treatment is presented from Feiringklinikken. Data on patients over and under 70 years have been analysed separately. The fraction of patients over 70 years admitted for catheterization increased significantly from 18.8% to 23.4% during the survey period. Angiography was associated with a low mortality of 0.04% and incidence of cerebrovascular complications with 0.1%, with no increased risk in patients over 70 years. The proportion of patients treated with PTCA increased significantly during the survey from 25% to 39% for patients over 70 years and from 31% to 42% for patients under 70 years (p < 0.01). The initial success rate of PTCA was 89% and 92% for patients over and under 70 years respectively (not significant). The rate of serious complications was low in both age groups, 3.2% and 1.0% in patients over and under 70 years respectively (p < 0.01). Older patients can be examined invasively with low risk of complications. A substantial number of patients, also among the elderly, can be treated safely with PTCA with good initial results. Thus, elderly patients should be offered the benefit of invasive diagnosis and treatment for coronary heart disease. PMID- 7770852 TI - [Celiac disease in the elderly]. AB - Coeliac disease appears at all ages and increasing prevalence in advanced age has been reported. We registered and followed up all coeliac patients during an 11 year period. The article describes the occurrence in elderly persons. Data were collected on symptomatology, laboratory test results, complications, dietary treatment, and progress. A total of 69 coeliacs were registered, giving a crude prevalence of 148/100,000. 13 patients (19%) were 65 years old or older at the time of diagnosis. Mean estimated diagnostic delay in this group was 21.5 years (range 5-40). The symptomatology was uncharacteristic in most patients and not dominated by malabsorption symptoms. Laboratory investigations were generally unhelpful for diagnosis. There was a high frequency of associated disorders, notably malignant diseases. Histology is a sine qua non in the diagnosis of coeliac disease, especially in elderly patients. Wide indications for biopsy are strongly recommended in this age group. PMID- 7770853 TI - [Malignant hyperthermia--still a current and dangerous problem]. AB - Malignant hyperthermia is a potentially fatal condition inducible by volatile anaesthetics and/or suxamethonium in genetically susceptible individuals. A disturbed calcium homeostasis in skeletal muscle (possibly in the ryanodin receptor) results in elevated myoplasmatic calcium. The latter causes muscle contraction and a hypermetabolic state, clinically observed as rigidity, fever, hypercarbia, metabolic acidosis and hyperkalemia. Arythmia ensues. Dantrolene inhibits the release of calcium and can halt the process if the diagnosis is made early. A fatal incident of probable malignant hyperthermia in a 13 year old boy is described and evaluated according to a multifactorial clinical grading scale. The value of the in vitro contracture test to diagnose malignant hyperthermia is discussed. Suggestions concerning the treatment of masseterspasm rigidity, an acute episode of malignant hyperthermia, and safe anaesthesia for susceptible patients are presented. PMID- 7770854 TI - [Transfusion-associated graft-versus-host disease. Increased risk when using HLA matched donors]. AB - For 30 years it has been known that immunodeficient patients can have a fatal reaction to transfused blood components containing viable lymphocytes. This risk of a transfusion-associated graft-versus-host reaction can be totally eliminated by irradiation of the blood prior to transfusion. Immunocompetent individuals can have this potentially fatal reaction if the blood donor is homozygous for one of the HLA-haplotypes of the recipient. The probability of this coincidence is low when donor and recipient are unrelated, but considerably higher when they are genetically related. When HLA-matched blood platelets are indicated for transfusing patients refractory to random platelets, the platelets must always be irradiated with minimum 25 Gy, since a large proportion of the donors will be homozygous with one of the HLA-haplotypes of the recipient. PMID- 7770855 TI - [Epilepsy]. AB - Epilepsy is a common neurological disorder which affects about 30,000 persons in Norway. 10% of the population may have experienced a single seizure, most of them occurring as a febrile seizure in childhood. Specialists in neurology and pediatrics are responsible for the diagnostic procedures and treatment. However, most doctors will see patients with seizures. This must be recognized as a symptom with many causes, rather than as a specific kind of disease. The author briefly reviews diagnosis, classification and treatment, with special emphasis on aspects which may be of importance for the general practitioner. PMID- 7770856 TI - [Unusual intracranial infections]. AB - The frequency of intracranial infections caused by microorganisms which have been uncommon in Norway is increasing. Contributing factors are travel, immigration and acquired immune deficiency, either as the result of disease or medical treatment. This article presents some of these infections, and also briefly reviews some other unusual infections which should be considered as differential diagnoses in unclear disease of the central nervous system. PMID- 7770857 TI - [What kind of information does the health services give to children with asthma and their parents?]. AB - Good information to families who have children with bronchial asthma is essential for treatment and in helping the family to cope. The aim of this study was to find out what kind of information the parents meant they had received, their knowledge about asthma, and what sanitary measures had been taken at home. A questionnaire was sent to all children (N = 431) who, during a five year period, were entered into the records of the Department of Paediatrics, Innherred Hospital, Norway, with the diagnosis bronchial obstruction. A selected group of 55 children and their parents were also interviewed. The results showed that the parents were not satisfied with the information they had received about the illness and about effects and side effects of the medication. Furthermore, their knowledge about these matters was not satisfactory, judged both by themselves and by the interviewer. It was more difficult to quit smoking or to stop keeping animals than to do extra cleaning at home. Few parents were informed about their possibilities of receiving financial support and about patient organisations. Only in a few cases did the health service provide the school with information on the child's disease. PMID- 7770858 TI - [Exchange of information between community and central health authorities. Development of an EDP system for information processing in the communities]. AB - The Ministry of Health and Social Affairs has started a research program introducing information technology into the float of information between central and local authorities. The prospect is to make a better platform for statistics and planning. This article describes the process of designing a computer program designed to meet the needs of the local authorities. The result is a program that integrates sending and receiving of data with preparation of the local annual report. An evaluation revealed that the need of such computer tools and support is greatest in the small municipalities. PMID- 7770859 TI - [Confidentiality in HIV-infection/AIDS--a comment on the Communicable Disease Control Act]. AB - The new Communicable Diseases Control Act has come into force in Norway. It makes it compulsory for a physician to warn a third party if it is obvious that a HIV positive patient, with a high degree of certainty, puts the third party at risk of being infected with HIV. Some philosophers characterize medical confidentiality as an intransigent and absolute obligation, others as a prima facie duty. This article supports the latter view, but the author still argues that strict conditions have to be fulfilled before a physician should consider breaking medical confidentiality: The doctor must try repeatedly to gain the consent or co-operation of the patient involved. Possible negative long-term consequences for the preventive HIV-work support strict medical confidentiality. PMID- 7770860 TI - [The first Norwegian physician in the USA? John M. Kalberlahn emigrated 70 years before Cleng Peerson]. PMID- 7770861 TI - [Cooperation in health care services]. PMID- 7770862 TI - [Alcohol--not good for the brain?]. PMID- 7770863 TI - [Insomnia and hypnotics]. PMID- 7770864 TI - [Do physicians know this about amalgam?]. PMID- 7770865 TI - [Reporting adverse effects to the Reporting Center at the National Board of Health and Welfare]. PMID- 7770866 TI - [Acting as a physician, even on a bad day]. PMID- 7770867 TI - [Social inequality and health]. PMID- 7770868 TI - [Use of organs of executed prisoners]. PMID- 7770869 TI - [The prospects for using the new macrolide antibiotic azithromycin (Sumamed) in the combined treatment of periodontitis]. AB - Antibacterial activity of sumamed, a macrolide antibiotic, in respect of anaerobic microflora of the oral cavity, such as Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Str. sanguis and Staph. aureus, was assessed. The drug was found to be highly effective in respect of bacteroids (MPC90: 1,4 to 30 mg/mlMg/ml, this permitting the use of sumamed in the treatment of 9 patients with chronic generalized periodontitis in the exacerbation stage. Bacteriological and clinical control of the results of therapy demonstrated the drug efficacy in respect of periodontopathogenous flora, particularly as regards bacteroids and fusobacteria which maintain the inflammatory process in periodontitis. PMID- 7770870 TI - [The clinico-immunological characteristics of the course of recurrent aphthous stomatitis]. AB - Clinical and laboratory examinations of 86 patients with relapsing aphthous stomatitis making use of a complex of clinical, immunological, cytochemical, and microbiological methods, helped specify the clinico-anamnestic features in the course of this disease. An immunobacterial concept of the pathogenesis of relapsing aphthous stomatitis has been formulated; according to this concept, the disease is initiated by disorders of T and B immunity system and nonspecific defense factors, leading to increase of the content and virulence of oral microflora, and thus stimulating the bacterial sensitization of the organism of patients with relapsing aphthous stomatitis. PMID- 7770872 TI - [The use of eiconol in the combined treatment of lichen ruber planus of the oral mucosa]. AB - Clinical and laboratory examinations of patients with lichen ruber planus revealed diseases of the hepatobiliary system in 85%, pancreatic diseases in 29%, chronic gastritis with manifest secretory insufficiency in 32.5%, and fatty hepatosis in 17.5% of patients. Biochemical analysis of the peripheral blood in patients with the exudative hyperemic and erosive ulcerative forms of the disease revealed hypercholesterolemia and hypertriglyceridemia. Administration of eikonol in a dose of 6 g/day led to reduction of triglyceride level by 18% and of total cholesterol by 6%, the hypocholesterolemic and hypotriglyceridemic effect of the drug being more expressed in the patients with initially higher levels of these parameters. Eikonol therapy promoted an improvement in the clinical course of lichen planus. A positive time course of changes was observed in 69% of patients with the exudative hyperemic form of the disease (less expressed unpleasant subjective sensations, decrease of hyperemia of the buccal mucosa and of the size of foci of lesions, less pronounced papular pattern). In the group with the erosive ulcerative form of the disease only 18% of patients developed positive changes under the effect of therapy (epithelialization of erosions, attenuation of the inflammatory reaction, less expressed papular pattern). Combination of eikonol with applications of keratoplasties to the foci of lesions in patients with the erosive ulcerative condition brought about a better therapeutic effect, with the periods of epithelialization reducing by 7 to 10 days. PMID- 7770871 TI - [Experience in treating patients with lichen ruber planus by using a helium-neon laser]. PMID- 7770873 TI - [Diphtheria of the oral mucosa]. AB - High incidence of diphtheria became a pressing problem in recent years. The age structure of patients has changed. A specific feature of diphtheria in adults is a high share of toxic forms and a higher incidence of grave combined forms and rare localizations of the disease focus. The oral cavity proper is one of rare localizations of this infection. The authors examined 12 patients in whom the process was localized in various parts of the buccal mucosa: on the upper and lower lips, on the hard and soft palate, on the cheeks and tongue. Morphologic disturbances presenting as necrosis and inflammatory infiltration were detected in sites involved in the diphtheritic process. Changes whose manifestation was related to the diseases severity were found in zones adjacent to the foci. The authors come to a conclusion on a higher incidence of heretofore rare localizations of diphtheria than previously, this making difficult the diagnosis and treatment of the disease. PMID- 7770874 TI - [The use of the analgesic preparation Ketorol in the combined treatment of pulpitis and periodontitis]. PMID- 7770875 TI - [Ways to prevent and treat disseminated inflammatory diseases of the maxillofacial area and their complications]. AB - The authors analyze the results of diagnosis and treatment in 1062 patients with diffuse inflammatory diseases of the maxillofacial area and of complications of these diseases, such as mediastinitis, thrombosis of the cavernous sinus of the dura mater, meningoencephalitis. Improvement of the program of diagnosis and treatment helped improve the results: mortality from sepsis reduced from 50 to 26%. Approaches to prevention of progressive purulent infection are outlined. PMID- 7770877 TI - [The use of immunoenzyme analysis for the diagnosis of an anaerobic infection of the maxillofacial area]. AB - Solid-phase EIA was used to titer antibodies to polysaccharide and ultrasonic disintegrate antigens of the most incident agents of anaerobic infections of the maxillofacial area. Comparison of the results of EIA with polysaccharide antigens of B.melaninogenicus, B.asaccharolyticus, F.nucleatum, P.intermedius, and Str.sanguis and the results of bacteriological detection of these bacteria in a closed pyoinflammatory focus in 283 patients with maxillofacial abscesses and phlegmons brought the authors to a conclusion that the suggested EIA technique may be used to prove the contribution of these bacteria to the development of an inflammatory process in a patient. Data are presented on the frequency of detection of a diagnostically significant level of antibodies in patients with positive results of bacteriological investigation. PMID- 7770876 TI - [The complicated course of an acute inflammatory process: its early diagnosis and the treatment principles]. PMID- 7770878 TI - [Changes in the permeability of pigmented mineralized dental tissues for carbonate and chlorine (radioisotope research)]. PMID- 7770879 TI - [An analysis of the late treatment results in patients with odontogenic perforated maxillary sinusitis]. AB - The authors analyze the results of sparing sinusotomy in 685 patients with chronic odontogenic perforative sinusitis. This effective method helped appreciably reduce the incidence of complications after surgical treatment of the said patient population. PMID- 7770880 TI - [Changes in the oral microflora under the influence of pulsed periodic CO2 laser radiation in operations on the jaw bones]. AB - Effects of pulsed periodical laser exposure on oral microflora were studied. Bacterial growth was suppressed immediately after surgery if pulsed periodical CO2 laser was used. Later only quantitative changes in the bacterial composition were observed. Asepticism of laser radiation does not depend on the discreteness of laser beam, radiation frequency, pulse duration, but depended on the radiation power, exposure duration, and area of exposure. PMID- 7770881 TI - [The immune status of patients who have undergone reconstructive operations on the jaws using different types of transplants]. AB - Lymphocyte subpopulations were studied in 18 patients by flow cytometry using monoclonal antibodies before and after surgical repair of the mandible with different transplants. All the transplants used had a stimulating effect on the immunity system. The most marked changes in the time course of immunologic parameters were observed after transplantation of frozen bone and formalin treated grafts. PMID- 7770882 TI - [Immunological and biochemical indices during the use of hyperbaric oxygenation for treating patients with jaw deformities]. AB - Analysis of changes in immunological and biochemical parameters in patients operated on for congenital deformations of the jaw bones and improperly grown fractures showed that postoperative therapy including hyperbaric oxygenation sessions was conducive to increase of immunological reactivity in patients with initially reduced immunological reactivity. No changes in urinary excretion of hydroxyproline were observed in the patients with deformations of the jaws. PMID- 7770883 TI - [The prevention of intolerance for metal inclusions in the oral cavity]. AB - The authors assessed the informative value of the Nakatani-ryodaraku and I. A.Lednev's methods of electroacupuncture diagnosis used to rule out the development of intolerance to metal inclusions in the oral cavity. Intratok and Eledia devices were used. Preliminary results are encouraging. PMID- 7770884 TI - [The determination of oral care habits by surveying the children of Russia and Finland]. AB - Questionnaires were distributed among 1187 children aged 7, 9 and 12 living in Moscow, St. Petersburg, Helsinki and Kuopio and dental examinations of these children were carried out. Children together with their parents answered the questions concerning tooth cleaning, consumption of sweets, parents' education. Analysis of the results helped detect the population motivation to proper care of the oral cavity and time course of this motivation. PMID- 7770885 TI - [The immediate and late results of treating the teeth of children after trauma]. AB - A total of 132 teeth were treated in 105 children and adolescents aged 4, 5 to 15. All the patients were divided into 8 groups in accordance with the WHO classification; treatment policy and follow-up results over a period of 6 months to 5 years presented. Satisfactory remote results were attained in 91.8% of cases, in 4.9% complications occurred: pulp death and inflammatory processes, delayed formation of the roots of permanent teeth after a complete dislocation of deciduous ones. The authors enumerate the major components in comprehensive treatment providing the optimal conditions for formation of permanent teeth roots: removal of pulp irritation by special remineralizing dressings; splint application, if indicated; preservation of viability of at least the radical pulp, and in case of its death a timely removal thereof; creation of conditions for the tooth participation in mastication by replacing dental crown defects with fillings and dentures a month after injury. PMID- 7770887 TI - [Changes in the cranial bones in distal bite based on x-ray study data]. PMID- 7770886 TI - [The effect of the implantation of calcium-phosphate materials on the healing process in a periodontal defect (an experimental study on monkeys)]. AB - Experiments on 10 green monkeys were carried out to elucidate the effect of implantation of calcium phosphate materials on the course of healing of the periodontium after surgery. Periodontal defects were formed in the 654/456 area and filled with the implant on the right. The results were assessed two months later microscopically. The periodontium healed in both cases, but after implantation new bone formed at the site of the graft, cementogenesis and formation of new connective tissue adhesion were observed. The control sites healed with formation of cicatricial tissue. PMID- 7770888 TI - [An appliance for occlusion correction]. PMID- 7770889 TI - [The organization of dental service under market conditions and insurance medicine]. PMID- 7770890 TI - [A system of therapeutic, diagnostic and organizational measures in periodontal diseases]. PMID- 7770891 TI - [The clinico-anatomical tasks in a course on general pathological anatomy in a dentistry department]. PMID- 7770892 TI - [The characteristics of the development of caries in human dental fissures based on microhardness data. Its diagnosis, treatment and prevention]. AB - Hygienic status of the teeth was assessed after Fyodorov-Volodkina and Green Vermillion in 500 patients aged 26 to 68 consulted for caries, chronic and acute periodontitis. A good hygienic status of the teeth was observed in 70 subjects: the Fyodorov-Volodkina hygienic index was 1, the Green-Vermillion index O. The Fyodorov-Volodkina index from 1,7 to 5 in 430 patients, depending on the hygienic habits. Patients whose hygienic index was still unsatisfactory despite special training, were subjected to hygienic treatment of teeth with a drill fitted with a modified toothbrush, using water suspension of tooth powder, zink oxide, phosphate cement powder, or tooth paste. Hygienic treatment of teeth by this method proved to be highly effective. The duration of the procedure is 3 to 5 min. PMID- 7770893 TI - Curricula: already too comprehensive. PMID- 7770894 TI - Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol-anchored protein that carries Gregory, Holley, and Dombrock blood group antigens. AB - BACKGROUND: The high-frequency Hy and Gya antigens have been shown to reside on the same protein. Gy(a-) Hy-negative red cells are also Do(a-b-). A mouse monoclonal antibody, 5B10, was produced with specificity related to the human Gregory, Holley, and Dombrock blood group antigens. STUDY DESIGN AND METHODS: The antibody reacted in direct hemagglutination assays, and its specificity was investigated by radioimmunoassay, inhibition assay, and Western blotting. RESULTS: The 5B10 antibody failed to bind to abnormal paroxysmal nocturnal hemoglobinuria red cells and human erythroleukemia cell line K562, but it was weakly reactive with HEL cells. Red cells, but not other circulating hematopoietic cells, express the 5B10 antigen. The 5B10 antibody had a specificity similar but not identical to that of Gya. Gy(a-) Hy-negative red cells reacted extremely weakly with 5B10 antibody, but Gy(a-) Hy-negative red cells treated with a variety of proteases bound 5B10 antibody strongly. This suggests that these cells express a variant form of the protein recognized by 5B10. CONCLUSION: Identification of a monoclonal antibody to this glycosylphosphatidylinositol-linked protein opens a new avenue for investigation of the biochemistry, genetics, and function of the glycosylphosphatidylinositol linked protein that bears the Gya, Hy, and Do antigens. PMID- 7770895 TI - A comprehensive transfusion medicine curriculum for medical students. Transfusion Medicine Academic Award Group. AB - BACKGROUND: The Transfusion Medicine Academic Awards (TMAA) program, sponsored by the National Heart, Lung, and Blood Institute, has provided grants to medical schools to help them develop comprehensive curricula in transfusion medicine. In 1989, the TMAA Group published a set of comprehensive curricular goals for teaching transfusion medicine. The medical student portion of this curriculum has now been revised to reflect new developments in transfusion medicine and recent trends in medical school education. STUDY DESIGN AND METHODS: Two medical schools independently revised the 1989 curriculum for their students. Because significant similarities were noted between curricula of the two institutions, the two revisions were combined and submitted to all TMAA institutions for comment. As a result, a revised medical school curriculum was developed and approved by the TMAA Group. RESULTS: The revised curriculum consists of 28 objectives in six major areas of transfusion medicine. It is presented in its entirety in this article. CONCLUSION: The TMAA transfusion medicine curriculum should provide to medical schools a valuable resource for evaluating their teaching of transfusion medicine and should provide to medical school deans and curriculum committees an authoritative source of transfusion medicine expertise. PMID- 7770896 TI - Adverse reactions in blood donors with a history of seizures or epilepsy. AB - BACKGROUND: Individuals with epilepsy or seizure disorders are restricted from donating blood because of concern that they are prone to adverse donor reactions such as syncope and convulsions. A study evaluating whether that concern is warranted is reported. STUDY DESIGN AND METHODS: During a 2-year period beginning in 1987, blood donors in Maryland with a history of seizures were actively recruited by the American Red Cross. Adverse donor reactions were classified as "slight", indicating dizziness and nausea without loss of consciousness; "moderate," denoting syncope; and "severe," indicating convulsive syncope. RESULTS: There were 329,143 satisfactory blood donations; 613 individuals reporting a history of seizures donated blood a total of 723 times. Among donors with seizures, 186 (35.7%) were taking antiepileptic medication, and 61 (8.4%) had had one or more seizures in the preceding year. Individuals with seizures had a low incidence of adverse reactions (3.34%). Although this incidence was slightly higher than that in the entire population (2.24%), the difference was not significant. In particular, the risk of syncope with or without convulsive activity was low for people with seizures (0.21%) and not significantly greater than that in other donors (0.28%). CONCLUSION: Individuals with seizures or epilepsy are not at greater risk for adverse reactions after blood donation, and major restrictions on their participation as blood donors are not warranted. PMID- 7770897 TI - Hepatitis B surface antigenemia in blood donors following vaccination. AB - BACKGROUND: Detection of hepatitis B surface antigen (HBsAg) in recently vaccinated adults has not previously been reported. Transient detectable HBsAg has been observed in newborn infants immunized with a recombinant hepatitis B vaccine. STUDY DESIGN AND METHODS: Over a 1-year period, eight HBsAg-positive blood donors mentioned during donor notification that they had been vaccinated for hepatitis B virus 1 to 3 days before donation. Follow-up tests for HBsAg, antibodies to HBsAg, and antibodies to hepatitis B core antigen were performed 3 to 37 weeks after immunization. Four months later, a group of 19 donors who were coworkers received hepatitis B vaccination and then donated blood the next day. The coworkers were observed for duration of antigenemia. RESULTS: A total of nine cases of transient, confirmed (neutralizable) antigenemia occurred in healthy individuals who donated blood 1 to 3 days following vaccination with a recombinant hepatitis B vaccine. Follow-up testing showed no evidence of infection by hepatitis B virus. One (5.3%) of 19 blood donors vaccinated as a group had antigenemia at Day 1 but not on Days 2 and 3 following immunization. CONCLUSION: Individuals recently vaccinated for hepatitis B may test positive for HBsAg and become permanently disqualified as blood donors. Therefore, blood collection centers should consider temporary deferral of potential donors who recently received hepatitis B vaccine. PMID- 7770898 TI - Low-oxygen-affinity red cells produced in a large-volume, continuous-flow electroporation system. AB - BACKGROUND: Human red cells containing inositol hexaphosphate (IHP) have a lowered O2 affinity, though they are able to bind and carry about the same amount of oxygen as native cells. These modified cells therefore deliver oxygen more efficiently to the tissues, which is a property of potential clinical utility. Investigators set out to devise a system and procedure by which large volumes of IHP-containing red cells, suitable for transfusion, could be produced quickly and efficiently. STUDY DESIGN AND METHODS: The encapsulation of IHP into human red cells by use of several variations of static electroporation was performed to define the conditions necessary for optimal IHP incorporation and cell survival. These conditions were used as a starting point for optimization of a flow electroporation system. RESULTS: When fresh human red cells in a 35 mM IHP solution are subjected to three exponential pulses of field strength of 2.98 +/- 0.064 kV per cm per pulse and pulse length of 2.0 +/- 0.2 msec per pulse while flowing through a cooled electroporation chamber, the condition of the resultant cells, according to the criteria used here, is optimized. After storage for 24 hours in plasma at 37 degrees C, the cells show more than 85-percent survival (in vitro) and hematologic indices nearly identical to those of unpulsed control cells. The p50 value of these cells, however, has doubled to 50.4 +/- 2.0 torr. The processing time for 1 unit of blood is 90 minutes. CONCLUSION: These data indicate that the system described here can efficiently produce low-oxygen affinity red cells in volumes that are useful in clinical applications. PMID- 7770899 TI - The effect of solvent/detergent-treated plasma on red cells stored in vitro. AB - BACKGROUND: The potential use of solvent/detergent-treated plasma (S/D plasma) in transfusion practice raises concerns about the cytolytic effects that any residual solvent and detergent in the virally inactivated blood component might have on units of red cells in vitro, if the two components are mixed during preparation. STUDY DESIGN AND METHODS: S/D plasma was mixed with variously processed units of stored red cells, in vitro, to evaluate the effect the residual solvent and detergent would have on cell membrane integrity. A paired protocol design was used in which half-units of red cells were exposed to S/D plasma (test), and the matched half-units were exposed to either the supernatant additive solution from the original red cell unit or standard fresh-frozen plasma (FFP) (control). After incubation for up to 5 days, the units were evaluated for evidence of hemolysis or changes in other red cell storage assays. RESULTS: This study showed that, for fresh additive solution red cells (AS-1), the 5-day storage plasma hemoglobin levels were comparable in the red cells exposed to S/D plasma (21 mg/dL) and in the paired half-units stored in the original AS-1 supernatant (31 mg/dL) (p > 0.05). Similar findings were recorded for stored AS-1 red cells (S/D plasma; 111 mg/dL vs. AS-1 supernatant, 147 mg/dL; p > 0.05); stored CPDA-1 red cells (S/D plasma, 133 mg/dL vs. FFP, 103 mg/dL; p > 0.05); frozen red cells (S/D plasma, 28 mg/dL vs. FFP, 18 mg/dL; p > 0.017); and stored irradiated AS-1 red cells (S/D plasma, 608 mg/dL vs. AS-1 supernatant, 726 mg/dL; p > 0.05). Comparable results were found for other assays, including levels of plasma potassium, osmotic fragility, and red cell antigen titer. CONCLUSION: These data show that S/D plasma does not induce red cell lysis even after 5 days of in vitro storage. These results are consistent with previous findings by this laboratory that platelets are not harmed by storage in S/D plasma. Red cells resuspended in S/D plasma and stored for up to 5 days maintain in vitro storage characteristics that are acceptable for the use of the cells in clinical transfusion practice. PMID- 7770900 TI - Collection of mobilized blood progenitor cells for hematopoietic rescue by large volume leukapheresis. AB - BACKGROUND: Mobilized blood progenitor cells rapidly reconstitute hematopoiesis in patients after dose-intensive chemotherapy. However, optimal timing and methods of mobilized blood progenitor cell collection have yet to be fully defined. STUDY DESIGN AND METHODS: The utility of large-volume leukapheresis (LVL; > 15 L blood processed) in collecting target doses of mononuclear cells (7 x 10(8)/kg) for use in autologous hematopoietic rescue was investigated. LVL was begun at a standardized interval (14 days) after a course of limited chemotherapy and subsequent daily recombinant human granulocyte-macrophage-colony-stimulating factor administration to mobilize blood progenitor cells into the circulation. With each LVL procedure, mononuclear cells, colony-forming units-granulocyte macrophage (CFU-GM), burst-forming units-erythroid, mixed colonies, total clonogenic progenitor cells, and CD34+ cells collected per kg of patient weight were counted. After high-dose chemotherapy and infusion of cryopreserved mobilized blood progenitor cells, the days needed for neutrophils to reach levels of > 0.5 x 10(9) per L and for platelets to reach levels of > 20 x 10(9) per L were recorded. RESULTS: In 14 previously treated cancer patients, an average of 28.9 +/- 4.9 L of blood was processed per LVL (n = 35) to collect medians of 2.5 x 10(8) mononuclear cells per kg (range, 1.0-7.4), 14 x 10(4) CFU-GM per kg (0 208), 27 x 10(4) clonogenic progenitor cells per kg (0-370), and 2.8 x 10(6) CD34+ cells per kg (0-112.5). Fifty-seven percent of patients (8/14) required one or two LVL procedures to collect adequate blood progenitor cells (range, 1-4). After dose-intensive chemotherapy, 13 patients received medians of 6.8 x 10(8) mononuclear cells per kg (range, 5.1-9.9), 53 x 10(4) CFU-GM per kg (9-208), and 12 x 10(6) CD34+ cells per kg (3.6-112.5). Rapid hematopoietic reconstitution occurred with 10 days (range, 8-12) and 9 days (6-15), respectively, for neutrophil and platelet recoveries. CONCLUSION: Scheduled LVL, beginning on Day 14 after the administration of granulocyte-macrophage-colony-stimulating factor following chemotherapy, is a convenient and efficient method of collecting blood progenitor cells. The mononuclear cells so obtained effected consistent and rapid hematopoietic reconstitution in a highly reproducible manner in a group of heavily treated patients. PMID- 7770901 TI - Prophylactic versus therapeutic platelet transfusion practices in hematology and/or oncology patients. AB - BACKGROUND: Platelet utilization has steadily increased throughout the past three decades. At the same time, there has been very little study of the current transfusion practices. STUDY DESIGN AND METHODS: A survey was conducted of institutional members of the American Association of Blood Banks (hospitals) that were actively involved in the care of pediatric and/or adult hematology and/or oncology patients. Inquiries were made relating to the extent of prophylactic versus therapeutic use of platelets, criteria used for prophylactic transfusion of platelets and type, and dose of platelets used. Data were analyzed according to patient age and type of hospital. RESULTS: Of 786 responding hospitals, 630 (80.2%) provided sufficient data for analysis; 126 of that 630 provided care for pediatric patients. The majority (60.9%) of responding hospitals had a minimum of four hematologists and/or oncologists. Eighty-four percent of hospitals reported transfusing some apheresis platelets. The dose of platelet concentrates most frequently used for adults ranged from 6 to 10, with pools of 10 more commonly used in community hospitals. More than 70 percent of hospitals reported transfusing platelets primarily for prophylaxis: 60 percent of hospitals set the threshold platelet count for prophylactic platelet transfusion at 20,000 per microL, with approximately 20 percent each transfusing at higher and lower levels. A platelet count of 50,000 per microL was most frequently required for performance of a minor invasive procedure. CONCLUSION: The data from this study show that the majority of institutions use prophylactic platelet transfusion in both pediatric and adult hematology and/or oncology patients. However, there is considerable variation in platelet transfusion practice. PMID- 7770902 TI - Prevalence of antibodies to human T-lymphotropic virus types I and II in volunteer blood donors and high-risk groups in northwestern Greece. AB - BACKGROUND: In addition to human immunodeficiency virus, human T-lymphotropic virus types I and II (HTLV-I/II) is prevalent among blood donors in the United States. In Greece, there are no epidemiologic data regarding the prevalence of HTLV-I/II among volunteer blood donors and high-risk groups. STUDY DESIGN AND METHODS: To determine the prevalence of HTLV-I/II infections in northwestern Greece, a seroepidemiologic study was conducted among volunteer blood donors, multiply transfused patients, heroin addicts, and chronic hemodialysis patients. The subjects were tested for serologic evidence of HTLV-I/II infection by enzyme immunoassays and specific protein immunoblot confirmatory test. RESULTS: None of the volunteer blood donors and heroin addicts had detectable antibodies to HTLV I/II. Only 1 (1.45%) of the 69 multiply transfused patients had indeterminate results, while 2 (1.2%) of 163 hemodialysis patients were positive. CONCLUSION: In northwestern Greece, routine screening for HTLV-I and HTLV-II infections does not appear to be required. However, the finding of seropositivity among hemodialysis patients requires further evaluation of the origin of the infection, as its zero prevalence in this population seems to exclude transfusion transmission. PMID- 7770903 TI - Red cell alloimmunization after a bone allograft. AB - BACKGROUND: Alloimmunization to blood group antigens other than ABH after bone allografting is uncommon. To date, examples of alloimmunization to blood group antigens other than ABH have been limited to the Rh system. CASE REPORT: A 20 year-old woman received an allogeneic bone graft following resection of an osteosarcoma. The patient had received no blood components and denied any pregnancies. Alloimmunization was detected and alloantibodies were identified by standard serologic techniques. Fourteen months after the bone graft, anti-Fya and anti-Jkb were identified in her serum. CONCLUSION: Alloimmunization to blood group antigens other than ABO and Rh may follow bone allografting. PMID- 7770904 TI - Vascular erosion caused by a double-lumen central venous catheter during therapeutic plasma exchange. AB - BACKGROUND: The use of large-bore double-lumen dialysis catheters has simplified the procedure of therapeutic plasma exchange, but these catheters are associated with unusual and possibly life-threatening complications. CASE REPORT: A 46-year old black man was admitted to the hospital with acute onset of paresthesia and weakness. A diagnosis of Guillain-Barre syndrome was made. Plasma exchange therapy was instituted by peripheral venous access. After three such exchanges, a double-lumen central venous catheter was placed via the left subclavian vein on hospital Day 7. The patient experienced a sudden onset of severe chest pain and dyspnea during the fourth plasma exchange. He became diaphoretic and hypotensive and experienced tachycardia. The apheresis procedure was stopped. Because of worsening respiratory distress, endotracheal intubation was performed. A chest x ray revealed a large right pleural effusion. The central venous catheter was removed. A chest tube was placed, and a large amount of bloody fluid was drained. Several days later, the endotracheal and chest tubes were removed. CONCLUSION: An unusual complication of the use of a central venous catheter, erosion of the superior vena cava, occurred during therapeutic plasma exchange. Prompt recognition of this complication and appropriate therapy can be life-saving. PMID- 7770906 TI - ISO 9000 quality standards: a model for blood banking? AB - The recent American Association of Blood Banks publications Quality Program and Quality Systems in the Blood Bank and Laboratory Environment, the FDA's draft guidelines, and recent changes in the GMP regulations all discuss the benefits of implementing quality systems in blood center and/or manufacturing operations. While the medical device GMPs in the United States have been rewritten to accommodate a quality system approach similar to ISO 9000, the Center for Biologics Evaluation and Research of the FDA is also beginning to make moves toward adopting "quality systems audits" as an inspection process rather than using the historical approach of record reviews. The approach is one of prevention of errors rather than detection after the fact (Tourault MA, oral communication, November 1994). The ISO 9000 series of standards is a quality system that has worldwide scope and can be applied in any industry or service. The use of such international standards in blood banking should raise the level of quality within an organization, among organizations on a regional level, within a country, and among nations on a worldwide basis. Whether an organization wishes to become registered to a voluntary standard or not, the use of such standards to become ISO 9000-compliant would be a move in the right direction and would be a positive sign to the regulatory authorities and the public that blood banking is making a visible effort to implement world-class quality systems in its operations. Implementation of quality system standards such as the ISO 9000 series will provide an organized approach for blood banks and blood bank testing operations. With the continued trend toward consolidation and mergers, resulting in larger operational units with more complexity, quality systems will become even more important as the industry moves into the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770905 TI - Acute hemolytic transfusion reaction, a paradigm of the systemic inflammatory response: new insights into pathophysiology and treatment. PMID- 7770908 TI - Algorithms, coagulation monitoring, and transfusion practice. PMID- 7770907 TI - Autologous transfusion: current trends and research issues. National Heart, Lung, and Blood Institute Autologous Transfusion Symposium Working Group. AB - Dr. Toy concluded the meeting by summarizing the major controversial issues highlighted by the speakers. PABD PABD is, in principle, a safe and effective method for avoiding exposure to allogeneic blood in appropriate circumstances, and a substantial amount of clinical literature has been published to support its role. However, additional research is needed in the following areas: The optimal number of units that should be collected for specific surgical procedures to ensure maximum savings in use of allogenic blood and minimum wastage; The safety of PABD in patients, including a better understanding of which patients are at risk for complications, what the risks are, and what alternative collection strategies should be employed. Adequate control groups are needed in these studies; A definition of the transfusion trigger as it applies to autologous RBCs; An investigation of the role of rEPO in facilitating PABDs; The development of better collection logistics (e.g., double-unit collections) and storage protocols (e.g., improved additive solutions); and Additional studies of the costs associated with autologous blood collection and development of more cost effective strategies. Acute normovolemic hemodilution Much of the published literature related to hemodilution describes the concept and specific protocols; in contrast, relatively little clinical research relating to the efficacy of this technique exists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770909 TI - Coiled-coil regions in the carboxy-terminal domains of dystrophin and related proteins: potentials for protein-protein interactions. PMID- 7770910 TI - Learning about DNA polymerase function by studying antimutator DNA polymerases. AB - Mutant bacteriophage T4 DNA polymerases exist that appear primarily to reduce the frequency of AT-to-GC transitions when this [antimutator' phenotype is assessed by genetic methods. This observation disagrees with in vitro studies, which indicate that T4 antimutator DNA polymerases have increased proofreading abilities and effectively edit all types of base substitution errors. One explanation that reconciles the apparent in vivo mutational specificity of antimutator DNA polymerases with their biochemical properties is that the in vivo mutational specificity identifies mismatched primer-termini that are corrected less efficiently by the wild-type level of proofreading activity, but are corrected if proofreading is increased. PMID- 7770911 TI - The eubacterial transcriptional activator Lrp is present in the archaeon Pyrococcus furiosus. PMID- 7770912 TI - A protein splice-junction motif in hedgehog family proteins. PMID- 7770913 TI - The SWI-SNF complex: a chromatin remodeling machine? AB - The SWI-SNF complex plays a key role in the regulation of eukaryotic gene expression. Genetic studies in the yeast Saccharomyces cerevisiae suggest that one role for the complex is to antagonize chromatin-mediated repression of transcription. Recent biochemical studies indicate that S. cerevisiae and putative human SWI-SNF complexes use the energy of ATP hydrolysis to disrupt nucleosome structure. PMID- 7770914 TI - Arf proteins: the membrane traffic police? AB - Cofactor for cholera toxin; activator of phospholipase D; regulator of coat protein assembly; inhibitor of membrane traffic; ability to cause expansion of the endoplasmic reticulum and vesiculation of the Golgi; sensitivity to membrane phospholipids--each of these activities has been attributed to Arf proteins. Can a single molecular mechanism link them all? PMID- 7770915 TI - G beta gamma interactions with PH domains and Ras-MAPK signaling pathways. AB - G-protein-coupled receptor signaling and receptor tyrosine kinase (RTK) signaling are two mechanisms of transmembrane communication used by numerous extracellular agents and stimuli. The beta gamma-subunit complex of G proteins mediates many of the functions associated with G-protein-coupled receptor signaling and may even provide a means to link G proteins to RTK-initiated cascades. This connection may be mediated by the pleckstrin homology domain, a modular domain found in many signaling proteins that interact with G beta gamma. PMID- 7770916 TI - The mechanisms of DNA topoisomerases. AB - Recent structural and mechanistic studies, as well as the discovery of new enzymes in the DNA topoisomerase family, allow these enzymes to be classified into three groups. Each group reflects the evolution of three different mechanistic strategies to manipulate DNA topology. PMID- 7770918 TI - Working on the assembly line. PMID- 7770917 TI - Caring for your hybridization membranes. AB - Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses the time limitation for using nylon-based and nitrocellulose membranes for Southern hybridizations, and there are a few other helpful hints. For details on how to partake in the newsgroup, see the accompanying box. PMID- 7770919 TI - How I learned to stop worrying and love Cell. PMID- 7770920 TI - Donor-recipient microchimerism is not required for tolerance induction following recipient pretreatment with donor-specific transfusion and anti-CD4 antibody. Evidence of a clear role for short-term antigen persistence. AB - There is considerable current interest in the possibility that long-term graft acceptance in clinical solid-organ transplantation might be dependent upon the development of a microchimeric state between the donor and recipient. This possibility has been prompted by the observation that in some transplant patients cells of donor origin can be detected in peripheral sites such as the skin, and it has been proposed that these cells play an essential role in maintaining graft survival. The hypothesis that peripheral microchimerism is an absolute requirement for the long-term survival of solid-organ allografts was tested in a well-characterized model of transplantation tolerance in which adult recipient mice are pretreated 28 days before transplant with a single donor-specific transfusion under the cover of a depleting anti-CD4 antibody. Mice pretreated with this protocol accept donor-specific cardiac allografts (MST > 100 days) but reject those of a third party (MST 16.5 days). The protocol leads to operational tolerance in the long term in that donor-specific skin grafts show prolonged survival while those from a third party strain are rejected acutely. Since peripheral blood contains haematopoietic stem cells we speculated that the success of the anti-CD4/DST protocol might be dependent on the development of microchimerism. To address this possibility the DST was irradiated before administration under anti-CD4 antibody cover in order to prevent donor stem cells in the transfusion from establishing a microchimeric state in the recipient animals. Mice in this group rejected their grafts acutely (MST 12 days), suggesting indeed that stem cells might be very important in the success of this model. However, when the protocol was modified by giving three additional doses of irradiated whole blood to increase the possibility that recipient T cells would be engaged during antibody-induced immunocompromise, graft prolongation was restored (MST > 100 days). These results demonstrate that persistence of donor antigen at the time of anti-CD4 antibody treatment is critical for the induction of unresponsiveness in this model and show that microchimerism is not an absolute requirement for long-term graft survival. PMID- 7770921 TI - Split liver transplantation in Europe--1988 to 1993. AB - The shortage of liver grafts results in the fact that 8% of potential recipients die before receiving a graft. Liver graft division has therefore been proposed to maximize the current available liver graft pool. However, the question of benefit or additional risk for the recipient that this technique might carry remains unanswered. The European Split Liver Registry was opened in March 1993 and reviewed retrospectively the clinical experience obtained at nine European centers regarding the use of split liver transplants, during the five year period from March 1988 to March 1993. From 50 donor livers, 100 grafts were prepared: 2 grafts were discarded and the other 98 were transplanted in 53 children (2 times in 3 children) and 42 adults (2/42 in heterotopic position). Sixty-three grafts were implanted in an urgent recipient (half of whom had acute hepatic failure). Portal vein thrombosis, hepatic artery thrombosis, biliary complications, and retransplantation rates were 4%, 11.5%, 18.7%, and 18.7%, respectively. Most of these complications were unrelated to the technique itself. Actual 6-month graft survivals of elective and urgent orthotopic transplants were 80% and 61.3% in children, and 72.2% and 55.6% in adults; actual 6-month patient survival rates for similar groupings were 88.9% and 61.1%, and 80% and 67.7%, respectively. Similar rates are reported after conventional transplants in Europe. It is concluded that split liver transplantation is an efficient transplant technique that benefits both urgent patients who otherwise could have died before getting a graft in time and elective patients. PMID- 7770922 TI - Xenotransplantation of porcine and bovine islets without immunosuppression using uncoated alginate microspheres. AB - Uncoated spherical hydrogel microspheres (calcium alginate, nominal M(r) exclusion of > 600 kD) 800-900 microns in diameter were employed to prevent immune rejection of discordant islet xenografts isolated from pigs and cows. The islets were immobilized in the microspheres and injected into the peritoneum of 14 nonimmunosuppressed streptozotocin (STZ)-induced diabetic C57BL/6J mice. Four recipients received islet grafts from bovine calves, and 10 received islet grafts from pigs. In the control group of 15 diabetic mice implanted with nonencapsulated islets, 6 received i.p. porcine islets and 5 received i.p. bovine islets, whereas remaining 4 received porcine islets under the kidney capsule. Plasma glucose concentrations in recipients of the alginate-encapsulated islets promptly dropped from a preimplantation value of 498 +/- 47 (mean +/- SEM) to 142 +/- 6 (bovine) and 178 +/- 7 mg/dl (porcine) during the first wk. All the animals sustained these levels for at least 1 mo. Two mice implanted with bovine islets subsequently reverted to diabetes (plasma glucose > 250 mg/dl) at 43 days postimplantation. The remaining grafts maintained function for > 10 wk. In contrast, nonencapsulated islets failed to function, or sustained euglycemia for < 4 days. Mice receiving encapsulated islets showed a 23-38% gain in body weight during the first mo after implantation, compared with < 1% (P < 0.002) and 32% (P = 0.84) for the untreated diabetic (n = 6) and normal control (n = 6) groups. Immunohistochemical staining of long-term grafts (> 10 wk) revealed viable islets, with well-granulated alpha, beta, and delta cells; the external surfaces of the microreactors were free of fibrotic overgrowth and exhibited only occasional host cell adherence. Uptake studies with IgG and thyroglobulin (M(r) of 669 kD) suggest that the microreactors were permeable to molecules with a molecular weight of up to > 600 kD (including the various proteins of the complement system, M(r) of 24-570 kD). Spheres implanted in the peritoneum after only 1 wk stained positive for both IgG and for the C3 component of complement. These findings suggest that prolonged survival of discordant xenografts of porcine and bovine islets in the STZ diabetic mouse model can be achieved with uncoated alginate microspheres that are permeable to IgG and complement. The question of whether similar results can be achieved with uncoated alginate microspheres in higher animals remains to be fully determined. PMID- 7770923 TI - Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation. AB - The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean +/- SD; 5.3 +/- 1.7 days), whereas all six without PHVS died within 3 days (1.8 +/- 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 +/- 1.2 mmHg and 16.9 +/- 3.1 mmHg, respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7 during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation. PMID- 7770924 TI - Prevention of cancellous bone loss but persistence of renal bone disease despite normal 1,25 vitamin D levels two years after kidney transplantation. AB - Osteopenia has been observed to occur frequently after renal transplantation. The present study was undertaken to assess whether an immunosuppressive regimen combining cyclosporine with no or the lowest possible maintenance doses of glucocorticoid may prevent osteopenia after kidney transplantation. Thirty-four patients were prospectively followed for two years. Serial blood drawings were done for determination of serum indices of calcium and bone metabolism and an iliac crest bone biopsy was performed at time of transplantation. A second bone biopsy was done in 20 patients during the second year of observation. Creatinine clearance was 56 +/- 6 ml/min one year and 46 +/- 6 ml/min two years after transplantation. Serum parathyroid hormone levels were elevated in 24 patients at time of grafting, decreased significantly thereafter, but remained above the normal range. Ten patients had low or normal serum parathyroid hormone levels at time of transplantation and showed a significant increase after grafting. Two years after transplantation, the mean cumulative dose of prednisone was 5.9 +/- 0.5 g. After the first six months, 30-40% of the patients were not on maintenance doses of steroids. None of the patients experienced fractures, and cancellous bone volume was within or above the normal range in all repeat bone biopsies. It is of note that metabolic bone abnormalities did not resolve 1-2 years after transplantation despite normalization of serum 1,25 vitamin D levels. The histologic abnormalities at the time were consistent with the bone findings in renal failure suggesting resistance of bone to normal circulating levels of 1,25 vitamin D. PMID- 7770925 TI - Calcineurin activity is only partially inhibited in leukocytes of cyclosporine treated patients. AB - Measurement of the degree of immunosuppression induced clinically by drugs such as cyclosporine is an important but elusive goal. In lymphocytes in vitro, cyclosporine (CsA) blocks the phosphatase activity of the enzyme calcineurin, preventing cytokine induction. We sought to measure the degree of calcineurin blockade in patients on CsA. Calcineurin activity was measured in peripheral blood mononuclear cells (PBL) from stable CsA-treated renal transplant patients, compared with controls. Cytokine expression was assessed by challenging ex vivo PBL with calcium ionophore A23187 (5 microM) for 60 min and measuring interferon gamma (IFN-gamma) and interleukin 2 (IL-2) mRNA induction. In vitro, CsA inhibited both calcineurin activity and cytokine induction with an IC50 of 10-20 micrograms/L. In CsA-treated patients with therapeutic CsA levels (mean trough CsA blood level = 180 +/- 55 micrograms/L), calcineurin activity was detectable but reduced by 50% compared with controls (P < or = 0.001) and correlated with CsA trough levels (r = -0.390, P < or = 0.01). The induction of cytokine mRNA in such patients was not blocked, but was sensitive to CsA in vitro, suggesting that CsA is much less available in vivo in body fluids than it is for isolated cells in vitro. In lymphocytes of patients on CsA, calcineurin activity is reduced but 50% of the activity persists, permitting strong signals to trigger cytokine expression. Partial calcineurin inhibition may explain why the immune responsiveness of patients on CsA is reduced but still sufficient for host defense. PMID- 7770926 TI - The magnetic resonance renogram in renal transplant evaluation using dynamic contrast-enhanced MR imaging. AB - To assess the role of the dynamic gadolinium DTPA (Gd-DTPA) magnetic resonance (MR) renogram in differentiating various causes of renal allograft dysfunction, contrast-enhanced MR imaging studies were performed in 5 normal renal allografts, 5 patients with acute rejection (AR), and 7 patients with cyclosporine nephrotoxicity. Time-versus-signal intensity (SI) curves were plotted. Normal renal allografts showed a rapid increase and slow decay, with a definite peak in cortical (CX) SI curves (peak mean signal intensity (Amax 338.6 +/- 46.5). The outer medullary (OM) (Amax 306.5 +/- 59) and inner medullary (IM) (Amax 263.4 +/- 47.4) curves did not show a definite peak. The OM curve slowly reached a steady state and caught up with the CX curve. AR episodes were characterized by a blunted uprise and delayed peak of CX (Amax 180 +/- 70.9) and a low-amplitude vascular phase with a slow constant uprise of the inner medullary curve (Amax 120.35 +/- 42.4). The OM signal intensity curve (Amax 150.73 +/- 78) failed to catch up with the CX curve. The maximum amplitude of SI curves in CsA-induced allograft dysfunction were low, with no definite peak, and CX, OM, and IM curves ran parallel to each other with a constant gap. Dynamic Gd-DTPA, MR imaging is a noninvasive technique that shows distinct characteristics in acute rejection, cyclosporine nephrotoxicity, and normally functioning renal allografts. PMID- 7770927 TI - An analysis of renal function in pancreas-kidney and diabetic kidney-alone recipients at two years following transplantation. AB - Pancreas-kidney recipients (SPK) are at higher risk for rejection than diabetic kidney-alone recipients (KA), and thus generally receive higher doses of maintenance immunosuppression. This has lead to concern that the potential benefits to renal function, brought about by posttransplant euglycemia, may be negated by the nephrotoxicity of immunosuppression. We therefore sought to compare patterns of renal function in diabetic patients following SPK and KA transplantation. Serum creatinine levels, corrected glomerular filtration rates (cGFR), and whole blood TDX cyclosporine levels were recorded on 25 SPK and 17 KA at 3, 6, 12, and 24 months posttransplant when patients were free of acute renal dysfunction. The SPK recipients had significantly higher cyclosporine levels at each of the measurement points as compared with the KA recipients (P < or = .01). In spite of these higher cyclosporine levels, the SPK recipients showed stable creatinine and cGFR levels throughout the study, as did the KA group until 24 months. At 24 months, the KA group experienced a rise in creatinine from 1.3 +/- .09 ng/dl at 3 months to 1.6 +/- .07 ng/dl at 24 months (P < or = 0.006). Urine albumin excretion was examined at 24 months, and 6 of 8 KA patients found to have abnormally elevated levels compared with only 3 of 9 SPK patients. These findings indicate that SPK recipients experience stable renal function despite significantly higher cyclosporine levels, while KA recipients demonstrate early signs of deteriorating function at the 2-year follow-up. PMID- 7770928 TI - Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment. AB - Thromboembolic complications constitute an important risk in renal transplant patients, in whom a hypercoagulable state is associated with immunosuppressive treatment, and the presence of hypercoagulability and hypofibrinolysis specifically with cyclosporine. Hypercorticism secondary to steroid treatment has been associated with a thrombophilic state and the presence of a reduced fibrinolytic potential in particular. The aims of this study were to first evaluate the fibrinolytic potential by the venous occlusion (VO) test in 19 renal transplant (RT) patients, and then compare these findings with those obtained in similar groups of normal subjects and patients with Cushing's disease. The following tests were carried out before and after the VO test: euglobulin lysis time and t-PA and PAI-1 activities and antigen. Compared with normal controls, RT and Cushing's patients both showed a similar significant increase in PAI-1 activity and concentration. The VO test revealed a similar impairment in fibrinolytic potential in both the RT and Cushing groups. High and pathological PAI-1 levels before and after the VO test were consistent with a defective fibrinolytic potential due to the inhibitory effect of PAI-1 on plasminogen activation. A hypofibrinolytic state was found in 68.4% of RT patients. Our results suggest that an imbalance in the fibrinolytic system is a typical feature of RT patients one year after transplantation. Steroids appear to be the immunosuppressive drug mainly involved in determining thromboembolic risk after renal transplantation. PMID- 7770929 TI - Endocapillary glomerulitis in the renal allograft. AB - Endocapillary glomerulitis is characterized by an increase in number of mononuclear cells in the glomerular capillary lumina. This lesion has been described in the early posttransplant period, but its pathogenesis, relation to conventional rejection, and prognostic impact is not well known. Using the definitions, scorings, and gradings of the Banff system for classification and grading of histopathologic changes in the renal allograft, we have analyzed 444 consecutive renal allograft biopsies from the first 90 days posttransplant. Moderate or severe glomerulitis occurred in 13.5% of the biopsies. There was a strong tendency toward clustering of glomerulitis: if one biopsy from a patient had glomerulitis, there was a high probability that it occurred in other biopsies from the same patient. There was some correlation with conventional acute rejection, but 40% of all biopsies with glomerulitis had no rejection and 53% of all biopsies with rejection had no glomerulitis. Graft function at biopsy was nil or decreased in many patients, but this could largely be explained by the independent presence of primary graft dysfunction or conventional rejection, these conditions being a frequent indication for performing a graft biopsy. Moderate or even severe glomerulitis was, however, compatible with a functioning graft. No correlation between glomerulitis and active CMV infection was found. The one-year graft survival of grafts with early posttransplant glomerulitis was 66%. If early conventional acute rejection is taken into consideration, graft survival does not seem to be influenced by the presence of glomerulitis. Early posttransplant endocapillary glomerulitis may be a peculiar pattern of rejection with a pathogenesis different from that of conventional rejection, but the present investigation does not demonstrate any adverse effects on graft function or graft prognosis. PMID- 7770931 TI - Red cell alloantibody development associated with heart and lung transplantation. AB - The development and persistence of clinically significant red cell alloantibodies were studied in 1132 patients who underwent a heart and/or lung transplant at Harefield Hospital. Clinically significant antibodies were detected in 15 patients (1.3%) preoperatively and appeared in a further 15 (2.1%) of 704 patients followed up 1-404 weeks after surgery. Anti-D developed in only 1 of 52 D-negative recipients of a D-positive donor graft and in only 2 of 6 D-negative patients who were transfused with between 6 and 32 units of D-positive red cells. Most antibodies that appeared after transplantation remained detectable for only a few weeks. Antibodies detected preoperatively that reacted only with papain treated cells became persistently undetectable in 4 patients who were transfused with red cells expressing the corresponding antigen specificity. By contrast, antibodies detected preoperatively by indirect antiglobulin test were still detectable after periods of up to 260 weeks in 4 patients who received only antigen-negative red cells. Immunosuppressive therapy appeared to profoundly affect the natural history of red cell alloantibody production in these patients. The underlying mechanisms warrant further study. PMID- 7770930 TI - Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients. AB - Chronic hepatitis C is a common cause of viral liver disease in kidney transplant (KT) recipients. To assess the efficacy and safety of therapy with interferon alpha we conducted a prospective study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b (IFNa) 3 million units three times weekly (scheduled) for 6 months (group A). 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period (group B). All the patients in both groups had had stable renal function for at least one year. All patients in both groups had a positive HCV viremia at the beginning of the study. Patients of group A were treated for 142 +/- 34.8 days (range 65-168); elevated serum aminotransferase (ALT) levels decreased rapidly and significantly from 100.3 +/- 48.9 to 37.7 +/- 13.9 IU/L (P = 0.001); 10 patients (77%) were "responders," whereas the others experienced a decrease in ALT values but without reaching the normal ranges. With a mean follow-up of twelve months after discontinuation of IFNa therapy, 8 responders--i.e., 80%- relapsed within 1-20 weeks. Only 4 patients had no detectable HCV viremia at the end of the IFNa; two of them already have abnormal values of ALT. Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment. Side effects of IFNa (fatigue, anorexia, weight loss) were frequent, and 3 patients decided to drop out of the treatment. The hematological tolerance was good although there was a significant decrease in hemoglobin (11.9 +/- 1.7 vs. 13.4 +/- 1.7 g/dl; P = 0.0044). In group B, serum ALT levels did not significantly decrease (84.2 +/- 47.6 vs. 105.2 +/- 68.8 IU/L). At the end of the study period serum ALT levels were significantly lower in group A than in group B (37.7 +/- 13.9 vs. 84.2 +/- 47.6 IU/L, P = 0.013). The major concern in group A was the occurrence of 5 renal failures. Kidney transplant biopsies showed edema, no significant tubulitis, scarcely scattered interstitial inflammatory cellular infiltration, and mesangial thickening. Four patients received methylprednisolone pulses but renal function improved in only two cases. We were not able to discover predictive factors of renal failure. We conclude that IFNa therapy is effective in controlling disease activity--i.e., reducing amino-transferase levels in KT patients with chronic hepatitis C, although relapse and detection of HCV RNA after the cessation of treatment were observed, respectively, in 80% and 100% of patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7770932 TI - Immunohistochemical analysis of T cell phenotypes in patients with graft-versus host disease following allogeneic bone marrow transplantation. AB - Allogeneic bone marrow transplantation has become the therapy of choice in many cases of hematologic malignancy. In both matched related donor transplants--and, to a greater degree, in unrelated donor transplant situations--a major complication of the procedure is GVHD. This problem is caused by mature T cells in the graft, which also facilitate engraftment, and mediate an antitumor effect to reduce relapse. In order to further characterize the T cells that are present at the GVHD site of injury, we have studied 134 fresh tissue biopsies using immunohistochemical methods from 50 consecutive ABMT recipients clinically suspected of having acute GVHD. Antibodies specific for T cells, T cell receptor subsets, B cells, and NK cells were used to characterize the lymphocytic infiltrate in the biopsy tissue from GVHD patients. The data showed that the majority of lymphocytes that had infiltrated the epithelium or epidermis were CD3+ T cells. Using antibodies that distinguished the alpha/beta (beta F1) from the gamma/delta TCR (TCR delta 1)-expressing T cells, we observed that the lymphocytic infiltrates from involved tissues of the gastrointestinal tract, skin, and liver are almost exclusively derived from the alpha/beta expressing T cell subset, and are of the memory cell subset of T cells (CD45RO). This is in contrast to some examples from other disease states, in which a significant proportion of the lymphocytes that infiltrate the epidermal layers are of the gamma/delta type. PMID- 7770933 TI - Bone marrow cell transplants involving donors and hosts with haplotypes derived from spretus mice. AB - Intra-H2 recombinant inbred mice derived from matings between B10 (H2b) and B10.SP2 (H2sp2) mice, with an H2 haplotype derived from Mus spretus, have been used to map genes at H2. Recombinants 10115, 10484, R40, 9347, and 9950 were used as donors or hosts in bone marrow cell (BMC) transplants in irradiated mice. From previous studies of Mus musculus mice, the antigens (Ag) on BMC appear to be inherited recessively. The mechanisms offered include codominant inheritance of transacting genes that regulate expression of BMC Ag (Hh hypothesis) and codominant inheritance of class I Ag motifs capable of sending "negative signals" to effector natural killer (NK) cells (missing self hypothesis). Our results indicate that stem cell donors that express the same class I Ag, but differ at genes between Bat2 and Tnfa in the H2-S/D interval, can differ in immunogenicity of transplanted stem cells. The structural gene for the H2sp2 Ag appears to map telomeric of Bat2 and is codominantly inherited. An H2b gene capable of inhibiting expression of the H2sp2 Ag (or contributing to class I motifs capable of inhibiting NK cell mediated lysis of H2sp2 BMC) maps in the Bat2/Tnfa gene segment, but requires homozygosity for this function and may require the H2-Db gene as well. Although H2sp2 hosts reject H2b BMC, hosts (10115, 10484, R40, and 9347 strain) that are H2b in the centromeric, and H2sp2 in the telomeric, portion of H2 accept H2b BMC grafts. These two observations have not been made with haplotypes entirely of Mus musculus origin. The data do not support the Hh hypothesis, and are consistent with the missing self hypothesis only if the gene (requiring homozygozity for function) in the Bat2/Tnfa region codes for a particular protein or peptide that associates with Db to generate a "protective motif." PMID- 7770934 TI - A technique for porcine hepatocyte harvest and description of differentiated metabolic functions in static culture. AB - Current bioartificial liver devices are based on the use of a large mass of hepatocytes exhibiting differentiated metabolic function. The pig has become a source of interest for the acquisition of such cells-however, harvesting a large mass of highly viable cells has met with difficulty. This study describes a technique for harvesting large quantities of hepatocytes at viabilities greater than 90% and also describes several features documenting differentiated function. Pigs, 6 to 10 kg body weight, underwent in situ two-step whole liver perfusion (ethylene glycol tetraacetic acid and collagenase) and ex vivo cell harvest. Harvests yielded an average of 19.5 billion cells with an average viability of 94.6%. Hepatocytes were then entrapped in type I collagen (3 x 10(5) cells/well) and cultured in serum-free media for 5 days. Pig hepatocytes produced stable amounts of albumin and maintained cytochrome P-450 and glucuronidation activity over 5 days, as shown by the metabolism of lidocaine and 4-methylumbelliferone. These data indicate that pig hepatocytes can be harvested with high yields and can retain viability and differentiated function over at least 5 days of culture, and therefore should prove to be an excellent source of hepatocytes for bioartificial liver devices. PMID- 7770935 TI - Insulin action in previously diabetic rats receiving graded numbers of islets of Langerhans. AB - We characterized insulin sensitivity in islet transplanted rats receiving from 500 to 3000 islets. Male Wistar Furth rats made previously diabetic with streptozotocin (55 mg/kg) were infused intraportally with islets of Langerhans (500 islets: n = 8; 1000: n = 6; 2000: n = 6; 3000: n = 5) from syngeneic donors and compared with sham-operated controls (n = 7). At four weeks after islet transplantation, fasting blood glucose was not significantly different between groups (500: 5.1 +/- 0.3; 1000: 4.8 +/- 0.3; 2000: 5.1 +/- 0.3; 3000: 4.6 +/- 0.1; control: 4.7 +/- 0.2 mM; P = 0.6146), and fasting plasma insulin was also not different (P = 0.28). The acute insulin response to glucose (0.3 g/kg i.v.) was correlated with islet equivalent mass (r = 0.63, P = 0.004; transplant rats only); islet transplant animals presented a range of acute insulin secretion from 3 to 90% of control values. Insulin action was measured in vivo in fasted, conscious animals during a hyperinsulinemic-euglycemic glucose clamp with insulin infused at 29 and 72 nmol/kg/min. Despite a wide range of islet mass and insulin secretory capacity, there was no significant difference in the glucose infusion rate between islet groups at either insulin level (P = 0.8211, P = 0.8021). There was also no difference in the glucose infusion rate normalized to the prevailing insulin level (P = 0.1638, P = 0.2302). Thus, our results demonstrate that the islet transplanted rat is consistent with other animal studies and human studies illustrating that a diminished insulin secretion does not necessarily precipitate insulin resistance. PMID- 7770936 TI - In vivo soluble tumor necrosis factor receptor release in OKT3-treated patients. Differential regulation of TNF-sR55 and TNF-sR75. AB - Administration of monoclonal antibodies to CD3 triggers acute and massive release of several cytokines, including tumor necrosis factor alpha (TNF-alpha), essentially T cell-derived. This cytokine release is responsible for the spontaneously reversible acute clinical syndrome observed in most OKT3-treated patients. We found that the first OKT3 injection in human renal allograft recipients led to the release in significant amounts of soluble TNF receptors (TNF-sR55 and TNF-sR75) that are considered main natural inhibitors of TNF bioactivity. As for OKT3-induced TNF-alpha, peak TNF-sR levels were observed 1 hr postinjection, and this release was limited to the first monoclonal antibody injection. A distinct regulation of OKT3-mediated release of TNF-sR75 and TNF sR55 was observed, since (1) in clear contrast with OKT3-mediated TNF-sR75 induction, TNF-sR55 release was completely blocked by a high dose of corticosteroids prior to OKT3 injection and (2) secretion of TNF-sR75 but not TNF sR55 correlated with immunoreactive TNF-alpha release. In hemodialyzed patients prior to transplantation and OKT3 treatment, a condition characterized by chronic TNF-alpha release, TNF-sR efficiently block TNF bioactivity. In contrast, the system is overwhelmed by the massive acute TNF-alpha release that follows the first OKT3 injection: in such a condition TNF-sR looses its capacity to counteract TNF bioactivity. PMID- 7770937 TI - DLA-identical marrow grafts after low-dose total-body irradiation. Addition of viable donor peripheral blood mononuclear cells does not enhance engraftment. PMID- 7770938 TI - Site-specific immune suppression with topical cyclosporine. Synergism with combined topical corticosteroid added during the maintenance phase. PMID- 7770939 TI - A simple method for transplanting discordant islets into rats using alginate gel spheres. PMID- 7770940 TI - Progressive plexogenic pulmonary hypertension following liver transplantation. PMID- 7770941 TI - Liver transplantation in a child with sickle cell anemia. PMID- 7770942 TI - Malakoplakia in the gastrointestinal tract of a liver transplant recipient. PMID- 7770943 TI - Xenotransplantation of UV-B-irradiated hepatocytes. Survival and immune response. PMID- 7770945 TI - Pros and cons of the hyperfiltration theory in human renal transplantation. PMID- 7770944 TI - Retention of endocrine function in the SCID-Hu pancreas mouse--a model for the development of human fetal islet tissue. PMID- 7770946 TI - Effect of stocking rates and anthelminthic treatments on weight gains in weaned Nellore cattle on improved pasture in the Brazilian cerrado. AB - The results are presented of 6 years of field trials with weaned Nellore cattle on improved pasture in the midwest of Brazil, using 2 stocking rates and 4 anthelminthic treatment regimes. The most profitable regime included treatments in May, June and September, which yielded an additional 41 and 42 kg of liveweight on the 2 stocking rates. No significant additional gains were obtained by treating during the rainy season, or by treating animals more than 24 months of age. The higher stocking rate (1.8 AU/ha) proved excessive on the improved pasture which deteriorated during the 6 year experimental period, yielding suboptimal liveweight gains. PMID- 7770947 TI - Theileria parva carrier state in naturally infected and artificially immunised cattle. AB - Rhipicephalus appendiculatus adult ticks, collected in the field from zebu (Bos indicus) and exotic (Bos tarus) cattle with high antibody titres to Theileria parva schizont antigen, transmitted Theileria parva infection typical of East Coast fever to susceptible cattle. Uninfected R. appendiculatus nymphs applied to naturally recovered zebu and exotic cattle kept under tick-free conditions in the laboratory for 16 and 7 months respectively, transmitted fatal theileriosis to susceptible cattle. Cattle immunised by the infection and treatment method were shown to be carriers of Theileria parva by examination of the salivary glands of ticks applied to them and by tick transmission. Three and 7 months after immunisation, Theileria parva infected lymphocytes were established in vitro from peripheral blood lymphocytes. This was the first demonstration, in vitro, of the existence of schizonts in Theileria parva (East Coast fever) infection carrier status. These studies show that cattle from endemic and epidemic areas of East Coast fever (ECF) become carriers thereby maintaining the T. parva population. The relevance of the findings in this study to the control of ECF by dipping, immunisation and treatment is discussed. PMID- 7770948 TI - Humoral antibody response in animals infected with virulent rinderpest virus. AB - Humoral antibody responses in cattle or rabbits infected with virulent rinderpest virus or lapinised rinderpest virus respectively were assessed. Rinderpest specific antibodies could be first detected 6 days post-infection. No correlation could be established between antibody response and the course of the disease in infected animals during the early stages of infection. The animals with fatal infection either did not respond or had a transient antibody response. A gradual increase in antibody titre from 7 days post-infection was observed in animals which ultimately recovered. PMID- 7770949 TI - An outbreak of bacillary haemoglobinuria in sheep in India. AB - An outbreak of bacillary haemoglobinuria was recorded in 60 out of 110 sheep in Ludhiana, Punjab, India. The condition was clinically characterised by fever, haemoglobinuria, constipation, weakness of hind quarters followed by recumbency, respiratory distress and death in 16 sheep. Haematological studies revealed moderate to severe degrees of anaemia associated with leucocytosis. Plasma gamma glutamyl transferase, alkaline phosphatase and creatinine phosphokinase activities were significantly higher in haemoglobinuric sheep. Babesiosis and copper poisoning were ruled out on stained blood film examination and from blood mineral profiles, respectively. Post-mortem examination of affected sheep revealed no gross changes. Pure cultures of Clostridium haemolyticum isolated from heart blood, liver, kidney and spleen of freshly killed sheep confirmed the disease. Parenteral administration of procaine penicillin was effective in the treatment of affected sheep. PMID- 7770950 TI - Isolation of multiple serotypes of bluetongue virus from sentinel livestock in Malaysia. AB - Sixteen isolations of bluetongue virus (BTV) were made from the heparinised bloods of 4 groups of cattle and sheep in Peninsular Malaysia. These viruses were typed as BTV serotypes 1, 2, 3, 9, 16 and 23. Multiple serotypes of BTV are apparently endemic in Malaysia and in other countries in the region. PMID- 7770951 TI - Reverse passive haemagglutination test in the diagnosis of infectious bursal disease. AB - The reverse passive haemagglutination test (RPHA) was used to detect infectious bursal disease (IBD) virus antigen in various organs of experimentally infected chickens and field cases. The results of RPHA were compared with those of agar gel immunodiffusion (AGID) and latex agglutination (LAT) tests. IBD antigen was detected in 86.4%, 80.4% and 80.5% of different organs by RHPA, LAT and AGID respectively. Although the differences are not statistically significant, the LAT is recommended because of cost and speed of obtaining results. PMID- 7770952 TI - Infectious bursal disease in 14-week-old turkeys in Nigeria. PMID- 7770954 TI - Sedentarisation of cattle farmers in the derived savannah region of south-west Nigeria: results of a survey. AB - The aim of this study was to assess the process and extent of sedentarisation among Fulani cattle owners in the derived savannah zone of south-west Nigeria. The results, based on a survey of 66 randomly-selected cattle owners, indicate an on-going process of settlement. Previously cattle owners visited the zone for dry season grazing but an increasing number were found to be settling and becoming mixed livestock/crop farmers. Generally herd sizes were larger among recent settlers but with longer duration of settlement and with cattle rearers' involvement in crop production, the herds became less mobile between seasons and herd size decreased and the proportion of farms with mixed zebu/trypanotolerant cattle herds increased. There was also evidence that some indigenous Yoruba crop farmers were becoming mixed farmers by purchasing cattle, hiring Fulani herdsmen for management, then taking up the management themselves. PMID- 7770953 TI - Milk yield of Chios-Ossimi crossbred ewes in relation to the yield of the parental breeds. AB - A study was carried out at Mallawi Research Station, 300 km south of Cairo, in which 16 Chios (CC), 31 Ossimi (OO) and 21 of their F1 crossbred ewes (50% Chios- 50% Ossimi (CO)). The CO crossbred ewes were mated to CC rams, whereas OO and CC ewes were mated to rams of the same breeds. The study included only ewes having single lambs in 2 lambing seasons; summer and winter. In the summer, total 8-week milk yield (suckling period) averaged 128.9, 53.4 and 77.1 kg in CC, OO and the crossbred ewes, respectively (P < 0.01). Total milk yield averaged 201.6, 65.0 and 110.2 and days of lactation were 151.1, 79.6 and 106.7, respectively (P < 0.01). In the winter, total 8-week milk yield averaged 138.6 (P < 0.01), 55.0 and 59.5 kg for CC, OO and the crossbred ewes, respectively. Total yield averaged 209.1 (P < 0.01), 65.9 and 76.5 kg and days of lactation were 153.3, 79.8 and 93.4, respectively (P < 0.01). PMID- 7770956 TI - [XXIIIm Maghrebin Medical Congress. Tunis, 9-11 May 1994. Abstracts]. PMID- 7770955 TI - Trypanosomosis and reproduction: II. Effect of Trypanosoma vivax infection on pregnancy and post-partum cyclicity in ewes. AB - The effect of infection with Trypanosoma vivax on pregnancy and post-partum cyclicity in ewes was investigated. Of the 5 ewes infected in the first trimester, 3 died without aborting and 2 after aborting. Intrauterine infection occurred in 2 of the foetuses removed at post mortem. Of the 5 infected in the third trimester, one ewe died without aborting, one lambed prematurely and 3 at term. Intrauterine infection occurred in one of the lambs born at term. None of the lambs were viable. The termination of pregnancy may be as a result of stress. The ewes infected in the third trimester commenced irregular cyclicity 13 to 23 days post partum. PMID- 7770957 TI - Electron microscopic studies of peripheral blood mononuclear cells in chronic type C hepatitis treated with interferon-alpha. AB - Electron microscopic studies of peripheral blood mononuclear cells (PBMC) in chronic type C hepatitis revealed several interesting structures after interferon alpha (IFN-alpha) therapy. Fifteen of 20 patients were treated with IFN-alpha. Tubuloreticular inclusions (TRI) were observed in only one patient who did not receive therapy. In contrast, TRI were observed in 10 of 15 (66.7%) patients who underwent the therapy for 2 weeks to 6 months. Cylindric confronting cisternae (CCC) were identified in the cytoplasm of PBMC in 4 of 16 (25%) patients who underwent the therapy. CCC were found only after IFN-alpha therapy. The appearance of both TRI and CCC in the PBMC was significantly correlated to IFN alpha therapy. Although there is little evidence about the morphogenesis of TRI and CCC, these structures may be a host response to IFN-alpha induced by hepatitis C virus infection. PMID- 7770958 TI - Intestinal spirochetosis and acquired immunodeficiency syndrome: ultrastructural studies of two cases. AB - Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. In case 1, a 48-year-old homosexual black man presented with a 1-month history of alternating watery diarrhea and constipation, which dissipated following the removal of two colonic hyperplastic polyps containing IS. In case 2, a 26-year-old homosexual black man presented with a 3-month history of persistent bloody diarrhea and was found to have chronic shigellosis and IS. Pathologic findings of IS were similar in both cases. Basophilic fringes typical of IS covered the surfacing colonic epithelium and consisted of dense growths of spirochetes adherent to and oriented perpendicular to the plasma membranes of the surfacing epithelium. The spirochetes measured 3 to 5 microns in length and 0.2 micron in width, contained four to eight axial fibrils, and closely resembled Brachyspira aalborgi ultrastructurally. These cases are notable because the histopathologic changes of IS were more extensive than generally described. There was involvement of both the right colon and rectum by IS in case 2, and in both cases there was extension of the IS down into the crypts of Lieberkuhn, spirochetal invasion of the colonic mucosa, and a conspicuous inflammatory response by macrophages in the underlying lamina propria. PMID- 7770959 TI - Ultrastructural pathology of Gerstmann-Straussler-Scheinker disease. AB - We report a detailed ultrastructural study based on a large series of samples from a recent case of Gerstmann-Straussler-Scheinker disease from the original Austrian family. Numerous PrP-immunopositive plaques dominated light microscopic neuropathology. Ultrastructurally, several types of plaques were observed: unicentric "kuru," multicentric, and neuritic. Dystrophic neurites accompanied amyloid plaques to differing degrees. Plaques were enveloped by astrocytic processes and invaded by microglial cells. A prominent astrocytic reaction accompanied abundant spongiform change. Unusual crystalloids were observed in mitochondria while another type of crystalloid was seen within lysosomes. We conclude that Gerstmann-Straussler-Scheinker disease is distinct also at the ultrastructural level. PMID- 7770960 TI - Immunolocalization of cellular fibronectins in the normal liver, cirrhosis, and hepatocellular carcinoma. AB - Cellular (c) fibronectins (Fn) differ biochemically, immunologically, and functionally from plasma fibronectins (pFn). Most existing data on Fn distribution in the normal and diseased liver require revision because those studies were based on reagents that did not distinguish pFn from cFn and predated the development of specific cFn monoclonal antibodies (Mabs). We immunostained cryosections of normal adult livers (n = 5), cirrhotic livers (n = 20), and livers with hepatocellular carcinoma (HCC) (n = 10) by the avidin-biotin-complex method with specific Mabs to the extradomains A and B (EDA, EDB) and oncofetal (Onc) isoforms of cFn. Selected samples were stained with an antiserum to pFn; fetal livers served as controls. Normal and cirrhotic livers showed EDA-cFn staining in the portal, septal, and perisinusoidal matrix; its distribution was more restricted than that of pFn. In cirrhosis, EDA-cFn reactions were strongest at sites of piecemeal necrosis and around proliferating ductules in biliary cirrhosis. EDA-cFn reactions were consistently most intense in the matrix of HCC. Distinct from adult normal and cirrhotic livers, reactions for EDB- and Onc-cFn were noted exclusively in most cases of HCC. We conclude that the only cFn isoform indigenous to the normal adult liver matrix is EDA-cFn. Enhanced EDA-cFn in cirrhotic livers may serve as indicator of active stromal remodeling. The restriction of EDB- and Onc-cFn to a large subset of HCC and the putative role of cFn in modulating cell-matrix adhesive interactions would suggest that the emergence of these molecules may be related to the variably invasive and metastatic properties of these tumors. PMID- 7770961 TI - "Aberrant elastic" in elastofibroma: an immunohistochemical and ultrastructural study. AB - Elastofibroma is a rare lesion characterized by the presence of abundant abnormal elastic fibers with a unique morphology, fibroblastic proliferation, and collagen deposition. Whether the altered morphology of the elastic fibers is a degenerative phenomenon or is due to abnormal elastogenesis is controversial. We studied fetal skin and three cases of elastofibroma by light microscopy and immunohistochemistry using an antibody to lysozyme, and one case of elastofibroma by electron microscopy (EM). Our previous studies have shown that normal elastic fibers in adult skin do not stain for lysozyme whereas abnormal elastic fibers in solar elastosis and pseudoxanthoma elasticum react positively for lysozyme. In the fetal skin and all three cases of elastofibroma the elastic fibers were negative for lysozyme. EM showed the abnormal flowerlike configuration of the elastic fibers, which consisted of a central core of normal or degenerating elastin surrounded by radiating spokes of granular and filamentous material of variable electron densities, suggesting that the structure and organization of the microfibrils is abnormal. The absence of lysozyme in the aberrant elastic did not differentiate whether there was excessive production of fetal or adult elastic. However, the excessive amount of microfibrils seen at the ultrastructural level suggests that there may be excessive fetal elastic production. The elastic fibers were intimately related to the fibroblasts and were often present within their caveolae, suggesting that the abnormal elastic fibers are produced by the fibroblast. Our study suggests that abnormal elastogenesis with subsequent degeneration plays a role in the production of the abnormal elastic fibers in elastofibroma. PMID- 7770962 TI - Ultrastructural localization of Helix pomatia agglutinin (HPA)-binding sites in human breast cancer cell lines and characterization of HPA-binding glycoproteins by western blotting. AB - Ultrastructurally, cells of five human breast cancer cell lines (MCF7, BT549, BT20, T47D, and HBL100) generally displayed many characteristics of their epithelial origin. The most distinctive features were observed in MCF7 cells, which consistently showed microvilli and submembranous granules. These ultrastructural findings served as a basis for localizing the binding sites of the lectin Helix pomatia agglutinin (HPA). After use of the pre-embedding method consistent HPA labeling of the cell membrane was obtained in all the cell lines, and in association with microvilli and submembranous granules in the MCF7 cells. The HBL 100 cells were not labeled by HPA irrespective of the method used. In addition, lysates from these cell lines were subjected to polyacrylamide gel electrophoresis and Western blotting with HPA to analyze these binding sites further. In the Western blots, however, lysates of JBL100 cells, in common with all those from the other cell lines, revealed a number of HPA-reactive bands, indicating the greater sensitivity of Western blots compared with the histochemical preparation. The principal band was of approximately 90 kDa, and it was suggested that this could be related to the transferrin receptor. PMID- 7770966 TI - [Community psychiatry--is it functioning?]. PMID- 7770964 TI - Proliferating thymolipoma: ultrastructural, immunohistochemical, and flowcytometric study. AB - A superior-anterior mediastinal tumor was excised from a 50-year-old man. The 207 g mass was encapsulated and multilobulated. It contained adipose tissue and abnormal thymic tissue. In some areas the thymic tissue was characterized by cords and nests of epithelial cells lying within either the adipose tissue or a myxoid matrix. Other areas were characterized by cortical thymic tissue with increased numbers of epithelial cells. Foci of normal medullary tissue were present. The prominent epithelial cells were immunoreactive for cytokeratin and nonimmunoreactive for vimentin, S-100, chromogranin, and parathyroid hormone. Flow cytometry showed that the lymphocyte populations were consistent with a late cortical thymic phenotype. The tumor was diploid. By electron microscopy, the prominent epithelial cells had desmosomes and a few tonofilaments. The cytoplasm contained additional organelles including mitochondria, polyribosomes, and occasional lysosomes. Nuclei were oval and had relatively smooth contours, prominent nucleoli, and moderate quantities of heterochromatin. Basal lamina was present around many nests and cords of cells. This is the first such study of a tumor with this histology. PMID- 7770963 TI - Divergent differentiative histogenetic lines in lung tumors: identification of histotypes with pure or mixed ultrastructural phenotype and their prognostic significance. AB - We performed an electron microscopic study of 50 lung tumors, previously diagnosed by light microscopy, and compared the results of the two techniques. Data analysis identified two ultrastructural phenotypes: pure and mixed. The former was characterized by a constant differentiative pattern and the latter by diverging differentiative histogenetic lines. We observed six differentiative lines as follows: squamous, glandular, neuroendocrine, villopodial, intestinal, and apocrine sudoriparous. Features of divergent differentiative lines were observed in 36 cases (64%), throughout the histotypes, sometimes with coexpression of more than one differentiation in a single case and/or cell. Adenocarcinoma was the histotype most frequently observed in pure form whereas most squamous cell carcinomas showed a mixed phenotype. This suggests that the histotype of the different lung tumors arises from a single glandular pluripotent cell, able to differentiate toward divergent differentiative lines. The clinical stage at onset and at the end of the follow-up indicates that the biologic behavior of lung tumors varies according to whether the ultrastructural phenotype is pure or mixed. PMID- 7770965 TI - Heterogeneity of acute myeloblastic leukemia without maturation: an ultrastructural study. AB - We demonstrated by ultrastructural examination that the leukemic blasts of 13 patients with acute myeloblastic leukemia (AML) without maturation (M1 in the French-American-British classification) showed heterogeneous features. In 7 patients, the leukemic blasts had a high level of light microscopic myeloperoxidase positivity (> 50%). Ultrastructurally, the cells were myeloblast promyelocytes with 100% myeloperoxidase positivity, and these 7 patients appeared to have typical AML. In contrast, the remaining 6 patients had leukemic blasts with a low myeloperoxidase positivity (< 50%) and heterogeneous features. Three had ultrastructural features of myelomonocytic or monocytic lineage, 1 had myelomonocytic cells associated with megakaryoblasts, and 1 had undifferentiated blasts. The former group had a better prognosis than the latter, indicating that ultrastructural analysis of M1 leukemia may help predict the response to therapy. PMID- 7770967 TI - [Community psychiatry in Copenhagen. Referrals during the first four years]. AB - The purpose was to estimate the number of referrals and patients, referral source, problems, diagnoses, demographic data and treatment offered in a community mental health centre. All referrals were systematically registered for statistical purposes. The referral rate stabilised at around 11 promille, point prevalence about 13 promille and one year prevalence above 20 promille. The centre was able to offer treatment to the majority of the patients referred. General practice referred about half of the patients, a quarter were self referred and one sixth each came from the social welfare services and the hospital. The number of patients referred from each GP varied considerably. As seen in other community mental health centres, patients with non-psychotic illness (2/3) and women (2/3) were in the majority. The older age groups were under-represented, and the social situation among the patients was worse than the general level in the district. It is concluded that a community mental health centre can fulfil the need for psychiatric treatment in an area and at the same time have the chronic psychotic patients as the priority group. PMID- 7770968 TI - [Renal side-effects of intraoperative and postoperative pain treatment with non steroidal anti-inflammatory drugs]. AB - Non-steroidal anti-inflammatory drugs (NSAID) are now commonly used in the treatment of postoperative pain. In normovolaemic conditions, prostaglandins do not seem to play a substantial role in maintaining renal function. However, numerous studies have shown that during activation of vasoconstrictor systems the synthesis of renal prostaglandins counteracts the vasoconstrictor effects and thereby maintains renal function. In animals, renal blood flow and GFR are markedly decreased when an NSAID is administered in the presence of renal hypoperfusion. Major surgery decreases renal function secondary to stimulation of the adrenosympathetic system and the renin-angiotensin system, and it has previously been demonstrated that maintenance of renal blood flow during laparotomy in dogs depends on an intact prostaglandin synthesis. Perioperative effects of NSAIDs are only sparsely investigated in humans, and studies on the effect on renal haemodynamics have not been presented. As in unanaesthetized volunteers, NSAID have been found to decrease the postoperative excretion of water, sodium and potassium. It therefore still remains unclarified whether general anaesthesia and surgery increase the risk of renal side effects of NSAIDs. Because of the potential risk of peri- and postoperative complications that may further deteriorate renal function, NSAIDs should not be used preoperatively, and not in patients in unstable haemodynamic states. PMID- 7770969 TI - [Hereditary optic nerve atrophy. A clinical-genealogical status over Danish families with Leber disease]. AB - An update on Leber's hereditary optic neuropathy (LHON) in Denmark disclosed 32 families with at least one live affected member, or recent disease onset (Table 1). Mitochondrial DNA analysis in the 30 families available for blood sampling identified the pathogenic mutation in all of them: ND4/11778 (26 families), ND1/3460 (three families), and ND6/14484 (one family). A previous distinct male dominance (sex ratio 4.6:1 in 157 ND4-patients with onset before 1968) seems to level (sex ratio 2.6:1 in 69 ND4-patients with onset in 1968 or later). Among possible explanations, we discuss improved diagnostic abilities and possible changes in women's alcohol consumption and smoking habits. PMID- 7770970 TI - [The effect of a three-year trial of a community dental care program for aged pensioners in Denmark]. AB - Recently, one Danish municipality established a programme of systematic dental care free of charge to citizens 67 through 70 years of age. The old-age pensioners were offered care according to the principles of the Danish Municipal Dental Service, including comprehensive curative and preventive care as well as oral health education. The present report describes the results achieved after three years of the programme in terms of changes in oral health status, oral health behaviour, and life-quality. Longitudinal data were collected for evaluation. Personal interviews were conducted at baseline (n = 216) and at follow-up (n = 235), comprising participants in the municipal programme as well as non-participants. Moreover, clinical follow-up data of participants were provided (n = 187, at follow-up). At base-line, 46% of all respondents had regular dental visits at least once a year and the proportion increased to 86% at the follow-up. A total of 75% participated in the municipal programme and the self-assessment of dental health improved significantly over time. The percentage of participants who reported poor function of dentures declined and, at follow up, less of the elderly felt embarrassed by teeth or preferred food that was easy to chew. The changes in self-reported oral health status were supported clinically by a reduction both in the number of untreated decayed tooth surfaces and in the number of teeth with gingival bleeding and pockets. Finally, gradually more attenders of the municipal service showed frequent oral hygiene habits and positive attitudes to oral health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7770971 TI - [Quality of data on computerized registration of postoperative wound infections]. AB - At the Department of General Surgery, Hillerod Hospital, the quality of data from a continuous registration of post-operative wound infection was evaluated. Data registered over a six-month period were compared with data available in caserecords and data from a questionnaire sent to the patients. During the period 1.2-31.7.1990 924 operations were registered in 864 patients. Eight hundred and ninety-five patient records could be traced and 770 questionnaires were sent. The remaining 125 were dead or had unknown addresses. Six hundred eighty-seven questionnaires were returned. The data-registered overall infection rate was 3.0%. The actual infection rate was 8.9%. Fifty-eight percent of the infections noted in the records were registered. Approximately 40% of the infections were diagnosed and treated in general practice only. It is concluded that in order to compare infection rates between departments, it is necessary to ensure that equal definitions and equal quality of the data are used. Strict routines in the department and a close contact to the general practitioners are essential to achieve a satisfactory quality of data. PMID- 7770972 TI - [Plasma total cholesterol, high density lipoprotein-cholesterol and triglycerides as risk factors for cerebrovascular diseases. A 12-year follow-up by the Osterbro survey]. AB - The aim of this study was to estimate the effect of plasma total cholesterol, HDL cholesterol and triglycerides on risk of cerebrovascular disease. The Copenhagen City Heart Study is a prospective population study with 14.223 and 12.411 participants in first (1976-78) and second (1981-83) examination, respectively, where plasma lipids were measured along with other variables. Acute cerebrovascular cases were recorded during 12-year follow-up and the associations between lipid levels and risk of cerebrovascular disease were estimated using the Cox regression model. Significantly increased risk of ischaemic cerebrovascular disease was associated with: total cholesterol levels > 8 mmol/l, decreasing HDL cholesterol, and increasing triglyceride levels. The association with HDL cholesterol and triglycerides was log-linear and relative risks (95% confidence intervals) corresponding to increase by 1 mmol/l were: 0.53 (0.34-0.83) and 1.12 (1.07-1.16), respectively. The relative risk for total cholesterol < or = 8 mmol/l was constant (non log-linear association). These associations did not vary significantly between women and men. PMID- 7770974 TI - [Subcutaneous fat necrosis of the newborn]. AB - Subcutaneous fat necrosis (SFN) of the newborn is an uncommon disorder, which occurs during the first years of life, and has been attributed to perinatal stress. Two typical cases are presented. This inflammatory disorder of adipose tissue affects primarily the back, buttocks, arms and thighs, and consists of sharply circumscribed, subcutaneous nodules and plaques. The lesions are red or violaceous and initially tender. Usually they involute spontaneously within months. Hypercalcemia, hypotonia, poor feeding, vomiting and fever are associated with SFN. The aetiology is still incompletely understood. Therapy is not required, except when associated with hypercalcemia. PMID- 7770973 TI - [Sensitivity of farmers to swine protein]. PMID- 7770975 TI - [Meta-analysis of magnesium therapy in myocardial infarction]. PMID- 7770976 TI - [Cancer morbidity among alcoholics]. PMID- 7770977 TI - [Sperm bank--a public task?]. PMID- 7770978 TI - [Water, health and Vibrionaceae infections]. PMID- 7770979 TI - [Psychosocial development of children with physical disabilities. Experiences from a Nordic study of 527 children with myelomeningocele]. AB - Data from a Nordic study on children with meningomyelocele (MMC), aged 4-18 years, are related to studies on the social and personal situation of children with physical disabilities. The data were collected in 1984 from medical records and by means of a postal questionnaire. In total 527 children with MMC and 7792 control children were included; the parents of the latter answered the same questionnaire as the former. As many as 80% of the children with MMC were integrated in ordinary school classes. However they had fewer friends and were less active outside home than children in general. Children with MMC need to develop autonomy and independence of their parents, especially with regard to their leisure activities and personal matters including personal hygiene. Concerning personal hygiene, independence could be developed for most of the children by systematic training, even among those who regularly use catheterisation. Both child and parents need support from multidisciplinary habilitation teams in order to develop the coping ability of the child. In school, along with assessment of the disabled child's learning ability, there is also a need to assess its personal and social functioning. According to studies by A. Antonovsky, people who experience their situation as comprehensible, manageable and meaningful are more healthy than others. It seems valuable to apply these three aspects to the way of thinking in work with habilitation. PMID- 7770981 TI - [The hepatorenal syndrome]. AB - Renal dysfunction and abnormal sodium-water handling are frequent in liver disease. The term hepatorenal syndrome (HRS) denotes a functional type of renal failure characterized by a progressive decrease in the glomerular filtration rate (GFR), greatly increased sodium retention, a high urine/plasma ratio of solutes, azotaemia, and oliguria. The main pathogenic feature is reduced renal blood flow (RBF), especially in the cortex. The kidney is morphologically intact and has been shown to rapidly regain normal function after transplantation to a recipient with a healthy liver. Three factors should be considered in the pathogenesis of HRS: 1) decreased liver function; 2) deranged haemodynamics, including abnormal blood pressure, blood volume, and blood flow distribution; and 3) deranged neuro humoral regulation. The prognosis in HRS is very poor, and therapy for HRS has proved disappointing. However future studies should be directed towards the reduced liver function and the haemodynamic abnormalities, especially the abnormal renal vasoconstriction. Implantation of a peritoneovenous shunt, paracentesis with plasma expansion, certain "blockers", and normalization of arterial blood pressure have reversed the HRS only in the more early stages. Liver transplantation is the ultimate treatment for the HRS. PMID- 7770982 TI - [Differential neuronal loss in the hippocampus in normal aging and in patients with Alzheimer disease]. AB - The causal relationship between the neurodegenerative changes that accompany normal ageing and those that characterize Alzheimer's disease is unclear. The high incidence of Alzheimer's disease associated with old age and the presence of its neuropathological signs in non-demented older individuals suggest that these two phenomena involve the same neurodegenerative processes and mechanisms and that Alzheimer's disease is an extension of normal ageing. On the other hand, the identification of environmental and genetic risk factors associated with Alzheimer's disease suggests the involvement of a specific disease process that is not related to normal ageing. The resolution of this fundamental issue is of importance in the design of investigative and therapeutic strategies. In this report, we describe differences in the regional patterns of neuronal loss, in the hippocampal region of the brains of Alzheimer's patients and normal ageing subjects, that indicate that Alzheimer's disease is not the manifestation of accelerated ageing, but the expression of a distinct pathological process. PMID- 7770983 TI - [The urethral plug--an alternative treatment of women with urinary stress incontinence]. AB - A developed urethral plug was evaluated for the treatment of women with genuine urinary stress incontinence. The plug consists of an oval meatal plate, a soft stalk and one or two spheres along the stalk with fixed distances between the meatal plate and the spheres. Inside the stalk is a removable semi-rigid guide pin to ease insertion. Forty women were randomly allocated to treatment with either the two-sphere or the one-sphere plug during period one (two weeks). In period two (two weeks) the patients used the other plug. They then continued with what they judged to be the better plug in period three (two months). Eighteen patients (45%) completed period three with the "preference" plug and 17 were subjectively and objectively continent or improved. Fourteen of these women preferred the two-sphere device. The plugs were equally effective in patients with mild or severe incontinence. Six women developed urinary tract infections and two of these had a plug in the bladder. The urethral plug is an effective treatment in a group of women with stress incontinence. Removal by hand is advisable in order to avoid retention of plugs in the bladder. PMID- 7770980 TI - [Hemoglobinopathies. Current therapeutic possibilities]. AB - In recent years, the number of immigrants has increased considerably in Denmark. Consequently, a series of new clinical pictures has appeared in the Danish health care system. Typical examples are the genetic diseases, the haemoglobinopathies. Most of the immigrants come from areas, where the gene frequency of these disorders is widely distributed, for instance the Mediterranean countries, the Middle East, Southeast Asia and Africa. Most frequent are the heterozygous thalassaemias, but also the number of patients with severe thalassaemia and other clinically important haemoglobinopathies such as sickle cell anaemia has also increased in recent years. The clinical problems concerning these patients focus on two important topics, namely genetic counselling of heterozygous individuals (in some cases combined with prenatal diagnostics) and the treatment of patients with clinically severe haemoglobinopathy. The only curative treatment of the haemoglobinopathies is allogeneic bone marrow transplantation, but this treatment can only be offered to a few of these patients. However, a variety of therapeutic options exist which can improve their prognosis and quality of life. Since the number of patients with these diseases will probably increase over the next years we find it relevant, based on typical case stories, to give a review of the present therapeutic possibilities for these disorders. PMID- 7770984 TI - [Medical audit in laboratory medicine. A description of the course and some results]. AB - All general practitioners of the Danish counties of Funen, Vejle and North Jutland were invited to participate in a medical audit concerning laboratory medicine organised by the Audit Project Odense (APO) in co-operation with the Consultative Arrangement for General Practice, emanating from the clinical/chemical departments of Funen. During three weeks the participants registered all clinical problems which would result in one or more laboratory tests. APO performed computer registrations and analyses of the results where upon each participant received a reply letter indicating the results of his own as well as the group's registrations. At a subsequent meeting the participants discussed the conception of "good general practice" as regards the use of laboratory medicine within defined clinical problems. The course of the audit demonstrated that the APO method is suitable for identification of a number of professional problems related to general practitioners' use of laboratory medicine and to reveal the variation in general practitioners' handling of laboratory medicine. Furthermore, the project showed that continuous quality development demands profound study of and research into the professional problems which the general practitioners encounter when using laboratory medicine. PMID- 7770985 TI - [Severe systemic infection with Vibrio vulnificus]. AB - Infections with Vibrio vulnificus are not common in Denmark, but in 1994 several cases were identified, probably due to the very hot weather conditions, with seawater temperatures above 20 degrees C. Two cases of infection with V. vulnificus are presented. PMID- 7770986 TI - [Fulminant myonecrosis and sepsis caused by Aeromonas hydrophila]. AB - A case of fatal bilateral lower extremity myonecrosis in a nonimmunocompromized man with septicaemia caused by Aeromonas hydrophila is described. Immediate surgical revision combined with treatment with new cephalosporins should be considered in the treatment of severe soft tissue infections, especially when the patient is known to have a trauma with waterborne contamination or is immunocompromised. PMID- 7770987 TI - [Angiotensin converting enzyme inhibitor renography should be done after acute intake of angiotensin enzyme inhibitor]. PMID- 7770988 TI - [Smoking cessation and nicotine therapy]. PMID- 7770989 TI - [Keys or chaos]. PMID- 7770990 TI - [Response to the comment by K. M. Sturmer on the contribution by B. Hausmann, K. Hudabiunigg: On the risk of fat embolism syndrome after intramedullary nailing in femoral fracture and thoracic injuries]. PMID- 7770991 TI - [MRI results in experimental muscle injuries]. AB - We performed an incision of standardized size and location on the suprascapularic muscle of 18 rabbits by a stab with a scalpel and measured the signal intensity of the muscle 2, 5, 11, 21, 35 and 64 days after injury (3 rabbits on each day). We did not find any detectable changes in the MRI pictures but a characteristic graph of the calculated T2-times (a mathematical procedure of the MRI software). The MRI changes correlate with the histopathological changes after muscle injury. The MRI method allows the evaluation of minor muscle trauma by the detection of a changed liquid content by using calculated T2 times. PMID- 7770992 TI - [Magnetic resonance tomography evaluation of the lower limb after compartment syndrome]. AB - For the purpose of follow-up of the disease as well as the availability of magnetic resonance imaging (MRI) as a method for diagnosing soft tissue changes 20 patients with imminent and manifest compartment syndrome were examined for their fluid content of the lower limb. Considering the normal side as well as 10 healthy volunteers a significant reduction of fluid content was diagnosed in the manifest compartment syndrome after fasciotomy in the late phase of disease (r = 0.49, p > 0.005, n = 29). This was interpreted as a sign of fibrosis. The patients with imminent compartment syndrome and fasciotomy (r = 0.83, p > 0.001, n = 19) demonstrated no significant changes compared to the normal volunteers (r = 0.91, p > 0.001, n = 40) as well as the normal compartments of the diseased lower extremities (r = 0.85, p > 0.001, n = 32). MRI is a useful method in the examination of soft tissue changes and underlines the importance of an early fasciotomy in case of imminent compartment syndrome. PMID- 7770993 TI - [New aspects in the treatment of complete and isolated diaphyseal fracture of the forearm in childhood]. AB - From 1984 to 1992 153 children were treated at the pediatric surgical department of the University of Mainz, of whom 19 had fractures of the radius, 9 of the ulna and 125 had a combination of both in the diaphysis of the forearm. Factors like patient's age, type of fracture and therapeutic methods were analyzed. One hundred and forty-one children were treated conservatively, 12 by operation. One hundred and one of these patients were healthy, when discharged (about 8 weeks after accident). Follow-up was possible in 69 cases. We found that occasional a remaining dislocation angle does not impair function: in 65 cases the result was "good" and "very good", but only "moderate" in 4 cases. These 4 children had been treated conservatively by reposition and plaster cast; 2 of these 4 children showed bone reconstruction without dislocation. Twenty-two of the 56 X-ray follow up's showed persisting dislocation. To prevent functional problems (2 of our cases) it is essential to obtain a very exact reposition of diaphyseal forearm fractures. Therefore we would recommend a more generous indication for operation, preferably using elastic-stable Nancy pins. PMID- 7770994 TI - [The "inserted" condylar plate]. AB - Twelve extensive segmental and comminuted fractures of the femur affecting the metaphyseal areas (7 times proximal, 5 times distal) and the diaphysis were treated with extremely long condylar plates (16 to 20 holes). The condylar plates were inserted via a proximal and a distal incision leaving the Musculus vastus lateralis intact at the fracture site in all cases. Following standard preparation of the blade position using the seating chisel, the condylar plate was inserted behind the musculus vastus lateralis with the blade pointing towards the surgeon. The condyles or the trochanteric area were tilted slightly and the plate was turned 180 degrees and driven home. No screws were inserted in the area of the fracture, in particular, lag screws were not used. Ten out of 12 fractures healed without problems, in 2 cases bone grafting was necessary. Three main observations resulted from analysis of the operations and subsequent clinical and radiographical assessments. In the presence of relatively intact soft tissue covering, an astonishingly good reduction of the fragments was achieved after restoration of leg length and extension. In the healing process, callus formed rapidly and provided medial support. The bone structure was found to be more homogeneous than in the case for plate fixation involving several screws at the fracture site around which considerable fluctuations in bone density frequently occur. The application of condylar plates behind the musculus vastus lateralis by only proximal and distal incision for osteosyntheses of extensive multifragmental fractures is a further development of bridge-plating and can be recommended for long fractures. PMID- 7770995 TI - [Can the results of cruciate ligament operations be arthrometrically evaluated? A comparison of subjective assessment, Lysholm score, clinical stability classification and measuring stability with the KT 1000 after complex knee injuries]. AB - In a long-term follow-up of 88 patients with complex ligament knee injuries we examined 70 of these who were operated upon between 1.4. 1988 and 31.3. 1990. We specifically looked at local complications, clinical results and knee stability, using subjective and arthrometrical (KT-1000) results 1 or 2 years after operation. The only parameters with a good correlation with stability were the clinical examination (Lachman-test) and the results with the arthrometer in the anterior-posterior translation. Stability after ACL-reconstruction with augmentation with a polydiaxonaon (PDS) augmentation band was physiological (2 mm under 89 N anterior-posterior traction) in 77% of all knees but only in 57% under maximal anterior-posterior manual stress. Neither the subjective outcome of Lysholm-Score correlated with arthrometry and clinical examination. PMID- 7770996 TI - [Protective air bags in traffic accidents. Change in the injury pattern and reduction in the severity of injuries]. AB - The effectiveness of air bags, drivers-side and passenger-side, as an additional passive safety system in motor vehicles was tested in a collective study in which 47 trauma centers in Germany participated. The inquiry was answered by 80% of 181 hospitals. The evaluation of a total of 119 air bag-protected patients involved in accidents, who were treated in German trauma centers in the year 1993 shows predominant minor injuries on the head-, cervical- and thorax-region. Some patients had superficial injuries caused by air bag in their face and chest area, such as abrasions and contusions. It is notable, that a large number of patients continue to suffer severe injuries (AIS 3+) in their lower extremities. The trend of the industry to equip more and more vehicles with air bags must be sustained. According to manufacturer statements, in 1994 already more than 60% of all mass produced vehicles in Germany will be provided with this modern passive safety system. PMID- 7770998 TI - Flow cytometric DNA/cytokeratin analysis of bladder lavage: methodical aspects and clinical implications. AB - Over the last few years cytological investigations of bladder lavage have gained ever-increasing importance in the diagnosis and follow-up of bladder tumors. Flow cytometric DNA analysis is searching for more objective ways to characterize tumor tissue beyond its morphological differentiation. Since the end of 1987 more than 400 bladder lavages have been analyzed both cytologically and by multiparameter flow cytometry. DNA/cytokeratin-8,18 antibody labelling of methanol-fixed single cells provides a standardized method which is not liable to disturbances and enables use in a routine laboratory. Aneuploidy was divided in several subgroups according to the DNA index. Proliferation of the urothelial population as a diagnostic parameter was investigated. Multiparameter flow cytometric measurement can identify and assess all subpopulations of bladder lavage such as inflammatory cells, squamous cells and squamous cell metaplasia. Cytokeratins enable a selective examination of the urothelial population after gating; the diagnostic accuracy for aneuploid tumor stem lines is markedly increased when compared to single-parameter DNA analysis. Higher specificity is reached by excluding falsely positive 'aneuploid' squamous cells; higher sensitivity is made possible by lowering the limit of detection for actual aneuploidy within a specimen, especially for near-diploid and tetraploid carcinomas. When compared to cytological malignancy grading, the aneuploidy rate is 26% in G1/2 tumors, 42% in G2 and 78% in G3 tumors (p < 0.005). More than half of the aneuploid bladder lavages with a negative or suspect cytology were diagnosed as tumor recurrences either histologically or cytologically in the following year. Moderately differentiated carcinomas with an aneuploid DNA distribution had a higher rate of recurrence than tumors with euploid distributions when treated curatively by organ-conserving therapy. DNA/cytokeratin analysis of bladder lavage enables an artefact-free measurement of tumor criterium aneuploidy; this is more specific and less sensitive than cytology. Due to the lack of separability of urothelial proliferation in euploid specimens, the aim to make flow cytometry a method equaling cytology cannot be reached. Therefore, the greatest value of flow cytometry is not in tumor screening, but in reliable detection of highly malignant aneuploid tumors at initial diagnosis, during therapy and recognition of recurrence of superficial bladder carcinomas. Reviewing the literature, flow cytometrically proven aneuploidy, especially triploid tumor stemlines, can be used to predict possible invasive growth. DNA/cytokeratin measurements are hence indicated when an exact assessment of prognosis can influence the therapeutic procedures. PMID- 7770997 TI - Androgen receptor alterations in patients with disturbances in male sexual development and in prostatic carcinoma. AB - The androgen receptor, a ligand-activated nuclear transcription factor belonging to the large superfamily of nuclear receptors, mediates the intracellular action of androgens. It plays a central role in male sexual development and in prostatic carcinoma as a target of endocrine therapy. We have looked for androgen receptor mutations as a cause of male sexual ambiguity and as a possible reason for failure of androgen ablation therapy on prostatic carcinoma. In 5 patients of 2 families with perineoscrotal hypospadia and undescended testes, we have identified a mutation ala596-->thr in the DNA-binding domain of the androgen receptor. This mutation interferes with DNA binding of the receptor. Reactivation of this mutant receptor by binding of an antibody or by interaction with other proteins and by exchange of the amino acid thr602-->ala indicates that the dimerization step is affected. A point mutation ser703-->gly was detected in a newborn male child with perineoscrotal hypospadias. This mutation decreased receptor-hormone affinity. As a consequence its transactivation activity was dependent on the androgen concentration. Although the molecular mechanisms of these two mutations are completely different, both resulted in partial androgen insensitivity and interfered with virilization in the affected patients. A different kind of mutation was present in a tumor specimen derived from an advanced therapy-resistant prostatic carcinoma. This point mutation resulted in exchange of valine-->methionine at amino acid position 715 in the receptor protein. In contrast to the former two mutations this receptor showed a gain in function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771000 TI - Testicular metastasis of cerebral malignant lymphoma. AB - Cerebral metastases of testicular malignant lymphomas have been reported. In this case a testicular metastasis secondary to a primary cerebral malignant lymphoma is presented. This unusual case does not correspond to the known metastatic pattern of malignant lymphoma. PMID- 7770999 TI - Morphological and functional changes in canine kidneys following extracorporeal shock-wave treatment. AB - Extracorporeal shock-wave lithotripsy (ESWL) has rapidly become established worldwide as a routine method for treatment of nephro- and ureterolithiasis. Although initial studies showed no tissue-damaging effect by the shock waves, we found, in an animal experiment using canine kidneys, that the ESWL-induced damage to the renal parenchyma is more marked than originally assumed. The damage is limited to the area that was focused on, and heals relatively rapidly by connective tissue encapsulation with final cicatrisation without any further residual effects being observed up to the present. This parenchymal damage is probably also the cause of the macrohematuria that is always observed during therapy. The resulting tissue damage is not extensive enough to cause a demonstrable reduction of function as measured by the usual methods (serum creatinine, creatinine clearance, isotopy renography, i.v. urography). In serum we observed a transient decrease of calcium, an immediate increase of lactate dehydrogenase, transaminases (SGOT and SGPT) and a delayed increase of alkaline phosphates. Creatinine, blood urea nitrogen, sodium, potassium and amylase remained within normal limits. In urine, a decrease of creatinine and an increase of glucose excretion were noted. We believe that these changes represent a relatively mild and transient damage of renal cells and do not reflect the occasionally heavy morphological changes observed after shock-wave exposure. The main clinical complication is the large subcapsular hematoma which, according to the present knowledge, could well result from a lesion of the larger peripheral vessels. Damage to other organs such as subserous colonic and small bowel hematomata are to be expected although they do not lead to clinical symptoms. PMID- 7771001 TI - Incontinence and vesical neck strictures following radical retropubic prostatectomy. AB - OBJECTIVES: To evaluate the incidence and severity of vesical neck strictures and urinary incontinence after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: Between August 1983 and December 1991, 481 consecutive patients underwent RRP by 1 of 2 senior surgeons. Strictures were treated by passing a urethral sound. Incontinence was measured by asking patients for a daily "pad count" of pads required to control urinary leakage. Results were compared to patient age, tumor volume, number of neurovascular bundles spared, preoperative urinary complaints, and previous transurethral resection of the prostate. RESULTS: Of 456 patients with adequate follow-up to determine stricture formation, 82.5% had no strictures, 6.8% required a single dilation, 3.7% required 2 dilations, 3.1% required 3 dilations, and 3.9% required more than 3 dilations. Risk of stricture formation was unrelated to every variable studied. Of 458 patients with adequate follow-up to determine recovery of continence, 80.1% required no pads, 8.1% required 1 to 2 pads a day, 6.6% required 3 to 5 pads a day, and 5.2% were totally incontinent 1 year or more after surgery. Incontinence was closely associated with postoperative urinary urgency. CONCLUSIONS: Strictures are a common but easily managed complication of RRP for prostate cancer. Despite substantial surgical experience, we report a somewhat higher rate of postoperative incontinence than other recently reported series. Our experience is more closely matched by published surveys of patient-reported complications after RRP. PMID- 7771002 TI - Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey. AB - OBJECTIVES: To assess patient responses to radical prostatectomy and its effects. METHODS: A national sample was taken of 1072 Medicare patients who underwent radical prostatectomy for prostate cancer (1988 through 1990) by mail, telephone, and personal interviews. The effects of the surgery and its complications on these patients' lives were studied through: (1) patient ratings of the extent to which sexual and urinary dysfunctions were "problems" in their lives; (2) two general measures of quality of life, the Mental Health Index and the General Health Index; (3) patient reports of how they felt about the results of treatment and whether they would choose surgery again. RESULTS: On average, dripping urine, particularly to the point where subjects were wearing pads, had a more significant effect on patients than loss of sexual function; incontinence had significant adverse effects on the measures of quality of life and self-reported results of surgery. Overall, postsurgical patients scored comparatively high on the quality of life measures (similar to a cohort of patients with benigh prostatic hyperplasia who had undergone transurethral resection of the prostate), reported feeling positive about the results (81%), and would choose surgical treatment again (89%). Nonetheless, there was variability in patient response to the effects of surgery. CONCLUSIONS: The results demonstrate the ability of many Medicare patients to adapt to adverse outcomes, such as loss of sexual function and incontinence. They also provide evidence of the variability of individual patients' responses to surgical results and reinforce the importance of individualized decision making for patients facing a decision about radical prostatectomy for prostate cancer. PMID- 7771003 TI - Contact neodymium:yttrium-aluminum-garnet laser ablation of the external sphincter in spinal cord injured men with detrusor sphincter dyssynergia. AB - OBJECTIVES: The purpose of this study was to determine the efficacy and safety of contact neodymium:yttrium-aluminum-garnet (Nd:YAG) laser external sphincterotomy as an alternative treatment of detrusor-external sphincter dyssynergia (DESD). METHODS: Twenty-two spinal cord injured men with video-urodynamically verified DESD underwent external urinary sphincter ablation using the contact Nd:YAG laser. Three patients with bladder neck obstruction required concurrent contact laser bladder neck incision. Preoperative urodynamic parameters of voiding pressure, bladder capacity, and residual urine were compared with those obtained 1 year postoperatively. RESULTS: Each procedure was performed with the Nd:YAG contact laser set at 40 to 50 W, with a total accumulated energy of 23,800 to 60,000 J for each patient. The mean duration of surgery was 45 +/- 21 minutes. Bladder voiding pressure decreased from 87 +/- 23 preoperatively to 47 +/- 11 cm H2O at 12 months (P < 0.01). Residual urine volume decreased significantly, from 122 +/- 77 to 33 +/- 19 mL at 12 months (P < 0.01), and bladder capacity remained unchanged at 174 +/- 84 and 230 +/- 92 mL (P = 0.57). Three patients were found to have recurrent sphincter obstruction 1 year after laser sphincterotomy. Two patients experienced complications associated with condom catheter urinary drainage and returned to the use of an indwelling catheter. One patient experienced diminished reflex erectile function postoperatively. No patient required blood transfusion. No deleterious effects on renal function or symptoms of autonomic dysreflexia were noted. CONCLUSIONS: External urinary sphincter ablation using the contact Nd:YAG laser compares favorably with electrosurgical techniques. PMID- 7771004 TI - Double-blind randomized crossover study comparing intracorporeal prostaglandin E1 with combination of prostaglandin E1 and lidocaine in the treatment of organic impotence. AB - OBJECTIVES: To study the efficacy of lidocaine 1% in relieving pain associated with intracorporeal prostaglandin E1 and to assess its effect on the pharmacological erection. METHODS: Twenty-two patients who had previously experienced pain with intracorporeal prostaglandin E1 injections were submitted to a double-blind randomized crossover study to evaluate comparatively the effects of intracorporeal prostaglandin E1 alone and in combination with lidocaine. The signed rank test was used for statistical analysis of the results. RESULTS: With prostaglandin E1 monotherapy (20 micrograms) 86.3% of patients experienced pain and 27.2% had an adequate erection. With combination therapy (prostaglandin E1 20 micrograms plus lidocaine 1% 1 cc) 45.4% of patients experienced pain and 57.8% of patients had improvement of pain compared with prostaglandin E1 monotherapy. The adequate erectile response rate with combination therapy was 63.6%; in addition, 31.8% of patients noted enhancement in the duration of erection. The signed rank test was significant for the pain response (P < 0.01) and for the degree of erection (P < 0.01). The signed rank test was not, however, significant for the increase in duration of erection after combination therapy. No significant side effects were noted after either injection. CONCLUSIONS: Lidocaine 1% can be safely and usefully combined with intracorporeal prostaglandin E1 in the treatment of erectile dysfunction with alleviation of pain and enhancement of erectile effect. PMID- 7771005 TI - Sequential penile ultrasound monitoring of patients treated with chronic intracavernous prostaglandin E1. AB - OBJECTIVES: Clinical outcome studies of prostaglandin E1 (PGE1) have shown a markedly decreased rate of palpable fibrosis and plaque formation. In this prospective study we investigate the potential of this agent to produce subclinical fibrotic changes. METHODS: Real-time high-resolution ultrasound scanning of the corpora was performed using a 7.5 to 10 MHz linear array transducer in 80 men on initiation of treatment with self-administered PGE1 and at quarterly intervals during the course of following (3 to 28 months). The dorsal portion of the penile shaft was scanned in the transverse and sagittal planes from base to glans for a side by side comparison of the cavernosal tissue, evaluating local abnormalities of tissue echogenicity. RESULTS: Palpable lesions were not detected in any men on quarterly follow-up examination. Thirteen (16.5%) men developed new echogenic foci not present on pretreatment scanning at the following locations: proximal corpus cavernosum, subcutaneous tissues, and corpus spongiosum. These changes were observed both as single and multiple lesions ranging in size from 1 to 10 mm. The presence of these findings was independent of the etiology of impotence, dose frequency, and duration of intracavernous therapy. CONCLUSIONS: The significance of these subclinical changes is unknown but their low incidence should be recognized when considering long-term intracavernous therapy. PMID- 7771006 TI - Prospective evaluation of neomycin serum concentrations after direct corpora cavernosa irrigation during penile prosthesis placement. AB - OBJECTIVES: To determine if toxic serum levels of neomycin are generated after direct corpora cavernosa irrigation during penile prosthesis placement. METHODS: We have used an infection prophylaxis technique that involves directly irrigating the corpora cavernosa tissue (through the corporotomy) with 0.5% neomycin solution. Serum neomycin concentrations were measured at 1 hour and 4 hours after irrigation in 13 patients undergoing penile prosthesis placement. A subset of patients who had preimplant and postimplant serum creatinine concentrations was evaluated for changes in renal function. RESULTS: The mean 1-hour postirrigation serum neomycin level was 1.2 micrograms/mL and the mean 4-hour postirrigation level was 1.2 micrograms/mL. These serum neomycin concentrations are lower than those thought to be necessary to produce nephrotoxicity or ototoxicity. Renal function was not significantly affected by the neomycin irrigation. CONCLUSIONS: Although aminoglycosides are ototoxic and neomycin has the highest nephrotoxic potential of the aminoglycosides, we conclude that direct irrigation of the corpora cavernosa with 0.5% neomycin solution does not produce significant systemic exposure to result in nephrotoxicity or ototoxicity. One-time prophylactic neomycin irrigation remains an effective, safe, and economic adjunct to penile prosthesis placement. PMID- 7771007 TI - Fascial closure of laparoscopic port sites: a new technique. AB - The laparoscopic operative procedure is not complete until the port sites are closed with a fascial suture. Herein, we report a simple new technique that uses a venous catheter for suture placement and direct laparoscopic visualization to secure the abdominal wall fascia and peritoneum. PMID- 7771008 TI - Use of a catheter limiter during intermittent catheterization. AB - We report on the use of a new device, the catheter limiter, to facilitate clean intermittent catheterization. The device limits the length of catheter entering the urethra. This provides a means to reduce the risk of mechanical injury and perforation, minimizes incomplete emptying, and improves safety and patient acceptance of intermittent catheterization. PMID- 7771009 TI - Adrenal cortical carcinoma with tumor thrombus invasion of inferior vena cava. AB - A case of adrenal cortical carcinoma with inferior vena cava (IVC) involvement is presented. Ultrasonography, computed tomography, and venacavography all presumptively showed a large mass over the upper pole of the left kidney with tumor thrombus in the IVC. However, aortography demonstrated that this mass was receiving its blood supply from the left inferior phrenic artery, aorta, and left renal artery. Radical surgery, including resection of the tumor and its adjacent organs (kidney, distal pancreas, spleen) and the tumor thrombus in the IVC, with the aid of cardiopulmonary bypass, was performed. We emphasize that adrenal cortical carcinoma can have tumor thrombi invading the IVC, and in such cases we suggest radical surgical removal of the tumor and the thrombus. PMID- 7771010 TI - Adult Wilms' tumor: prognostic and management considerations. AB - Wilms' tumor is the most common malignant tumor of the urinary tract in children but is rare in adults. Although histologically the tumors appear to be the same, successful treatment with multimodal therapy is much more common in childhood. We report on 2 patients with adult, anaplastic, Stage IV Wilms' tumor, one of which was discovered during pregnancy and was managed successfully with chemotherapy, including ifosfamide, carboplatinum, and etoposide. As more patients are properly identified and treatment outcomes with chemotherapeutic regimens documented, better therapeutic approaches in adult Wilm's tumor will be developed, resulting in improved survival. PMID- 7771011 TI - Femoral neuropathy following percutaneous nephrolithotomy of a pelvic kidney. AB - Management of nephrolithiasis within a pelvic kidney presents a novel challenge to the urologist. We report on a patient who underwent ureteral stent placement prior to extracorporeal shock-wave lithotripsy (ESWL). Following ESWL, the ureteral stent calcified at the vesical and renal ends, requiring "sandwich therapy" of percutaneous nephrolithotripsy, ESWL, and percutaneous nephroscopy. Percutaneous access to the pelvic kidney through a posterior approach was complicated by femoral neuropathy manifested by an ability to walk. With 6 months of aggressive physical therapy, the patient is now able to ambulate with difficulty using a walker. PMID- 7771012 TI - Penile Merkel cell carcinoma. AB - Merkel cell carcinoma of the genitalia is very rare and to date has been found only in vulvar mucosa. We describe an aggressive Merkel cell tumor in the frenulum of the penis with lymph node metastases, local recurrence, and eventually widespread dissemination. The primary tumor was associated with discontiguous squamous cell carcinoma in situ. This is the first report of Merkel cell (neuroendocrine) carcinoma in this anatomic site. PMID- 7771013 TI - Laparoscopic evaluation of indeterminate renal cysts. AB - OBJECTIVES: To determine the efficacy and safety of laparoscopic evaluation of indeterminate renal cysts. METHODS: Ten patients with indeterminate renal cysts (5 Bosniak type II and 5 Bosniak type III) underwent transperitoneal laparoscopic aspiration of cyst fluid for cytologic analysis with examination, biopsy, and excision of the cyst wall and base. RESULTS: All procedures were successful and without complications. All the lesions were benign. CONCLUSIONS: Laparoscopic evaluation of indeterminate renal cysts is safe and effective. The procedure alleviates patient anxiety about the nature of the lesion and obviates years of radiologic surveillance, thus reducing costs. PMID- 7771014 TI - Nitric oxide control of lower genitourinary tract functions: a review. AB - It is apparent that evolving concepts of the regulatory basis for functions in the pelvis must take into account the role exerted by nitric oxide. A recently characterized messenger molecule, nitric oxide has been associated with numerous physiologic processes. Intense investigations of this molecule have extended its importance to several genitourinary functions. Penile erection, micturition, peristalsis of the male excurrent duct system, contractile properties of the prostate, and lumbosacral spinal cord neurotransmission are all functions that may transpire under some degree of control by nitric oxide. Impotence, urinary obstruction, or ejaculatory problems, in turn, may represent alterations of nitric oxide production or action. The strategic manipulation of nitric oxide or its mechanism of action, possibly by pharmacologic means, may restore or produce desired functional effects. These possibilities, therefore, suggest that the advancing knowledge of nitric oxide in the genitourinary tract may be of enormous clinical value in the future. PMID- 7771015 TI - The loin pain--hematuria syndrome. PMID- 7771016 TI - Crossed fused renal ectopy and myelodysplasia. PMID- 7771017 TI - Pediatric ureteropelvic junction obstruction treated with retrograde endopyelotomy. PMID- 7771018 TI - Cimetidine in treatment of interstitial cystitis. PMID- 7771019 TI - The use of methylene blue in the identification of lymphoceles after renal transplantation. PMID- 7771020 TI - Femoral neuropathy following abdominal operations for genitourinary malignancies. PMID- 7771021 TI - In support of behavioral treatment for day wetting in children. PMID- 7771022 TI - Enuresis: a practical approach to a common problem. PMID- 7771023 TI - Immunotherapy for renal cell carcinoma: the era of interleukin-2-based treatment. PMID- 7771024 TI - Ejaculatory duct obstruction in the infertile male. PMID- 7771025 TI - Complications of cryosurgical ablation of the prostate to treat localized adenocarcinoma of the prostate. AB - OBJECTIVES: To review the complications associated with cryosurgical ablation of the prostate (CSAP) for localized adenocarcinoma of the prostate in the first 69 procedures performed at our institution. METHODS: A retrospective review of the charts of 63 patients (69 procedures) performed at our institution between June, 1993, and December, 1994, was undertaken with an emphasis on the complications, their management, and outcome. RESULTS: Thirty-seven of the 63 patients (59%) had at least one significant adverse event. Although no patient died or required a transfusion, other significant complications, including prolonged urinary retention, incontinence, sloughing of prostatic tissue, fistula formation, prolonged perineal pain, bowel dysfunction, and other problems were observed. CONCLUSIONS: CSAP is associated with a significant complication rate. These complications are more common in patients who have had prior CSAP or radiation therapy. Instead of decreasing with experience, the complication rate increased later in the series. In our patients, the complication rate increased after the use of an investigational urethral warmer was discontinued. CSAP is an investigational procedure of unproved long-term efficacy. It can be associated with substantial patient morbidity and should be performed under carefully controlled circumstances. Patients should be made aware of the potential for debilitating complications. PMID- 7771026 TI - Salvage radical prostatectomy after failed transperineal cryotherapy: histologic findings from prostate whole-mount specimens correlated with intraoperative transrectal ultrasound images. AB - OBJECTIVES: This study evaluates the potential for salvage radical prostatectomy after failure of transrectal ultrasound (TRUS)-guided percutaneous cryosurgical ablation of the prostate. An additional purpose was to determine the accuracy of intraoperative TRUS to delineate the extent of freeze destruction that results from cryosurgery. METHODS: Six patients with biopsy-confirmed, Stage T3 prostate cancer underwent salvage radical prostatectomy 3 to 10 months after failing prostate cryosurgery. Zones of freeze destruction (resolving coagulative necrosis) and residual adenocarcinoma were mapped on the coverslips of whole mount sections. Histologically proven zones of freeze destruction correlating to successfully treated prostatic tissue were compared to the hypoechoic ice ball treatment zones seen on intraoperative TRUS images. RESULTS: The whole mounts were found to contain necrotic areas of cryodestruction that appeared much smaller than predicted by intraoperative ultrasound. Each of the cases also contained residual viable adenocarcinoma. All patients are alive and clinically free of localized disease 0.5 to 12 months after salvage radical prostatectomy. CONCLUSIONS: Salvage radical prostatectomy offers an effective treatment option in patients who have failed transperineal cryosurgery of the prostate. Intraoperative TRUS predicted that the entire prostate would show freeze destruction. Whole-mount analysis, however, revealed areas of remaining unaffected adenocarcinoma and normal prostatic parenchyma. TRUS, therefore, overstimates the area of prostatic tissue destroyed by extreme cold. This finding challenges the assumption that the entire prostate is lethally frozen when its boundaries are included within the hypoechoic ice ball witnessed on TRUS. PMID- 7771027 TI - Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers. AB - OBJECTIVES: To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate. Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. METHODS: To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. RESULTS: We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali (P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali (P < 0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali (P < 0.024) was also observed. CONCLUSIONS: To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP. PMID- 7771028 TI - Holmium: yttrium-aluminum-garnet laser for endoscopic lithotripsy. AB - OBJECTIVES: To evaluate the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for endoscopic lithotripsy on patients diagnosed with urinary tract calculi. METHODS: Thirty-eight procedures utilizing transurethral ureterolithotripsy or percutaneous nephroureteral lithotripsy were evaluated: 5 renal calculi, 31 ureteral calculi (most in the upper ureter), 1 ureteropelvic junction calculus, and 1 bladder calculus. These were mainly in cases that, after being treated with extracorporeal shock-wave lithotripsy (ESWL), were contraindicated for further ESWL. Laser parameters included energy of 0.5 to 1.0 J/pulse and pulse rate of 5 to 10 Hz. RESULTS: Composition of calculi was determined in 26 procedures. The Ho:YAG laser was effective for fragmenting all types of calculi. Patient outcome evaluated at 6 weeks after treatment showed that 33 of 38 procedures (87%) were effective. Residual calculi in 4 of the 5 unsuccessful procedures were less than 5 mm in size and judged to be able to pass spontaneously. In the remaining procedure, the calculus was passed spontaneously 3 months after treatment. No severe damage to tissues or adverse effects to the body were observed due to the Ho:YAG laser. CONCLUSIONS: On the basis of these results, we determine that this wavelength is effective for lithotripsy in addition to its previously reported usefulness for soft tissue applications, and, thus, is a cost-effective and highly useful clinical device. PMID- 7771029 TI - Partial ureteral obstruction: a new variable and reversible canine experimental model. AB - OBJECTIVES: To develop a new experimental model of partial ureteral obstruction that is simple, reliable, variable, and reversible. METHODS: A 6 F ureteral catheter was inserted into the left ureteral orifice and was cut 2 cm distal to the orifice. The most distal part of the ureter was ligated around the catheter. The catheter lumen was partially obstructed by insertion of stylets of three different diameters. The catheter and the stylet were fixed inside the bladder. The model was tested in 12 dogs, which were stratified into three groups according to the diameter of the obstructing stylet. All the dogs were subjected to intravenous urography (IVU) and technetium-99m-mercaptoacetyltriglycine (99mTc MAG3) renal scan at 2 and 4 weeks following induction of partial ureteral obstruction. RESULTS: Three different grades of hydroureteronephrosis were obtained according to the diameter of the obstructing stylet. The IVU and 99mTc MAG3 renal scan studies were repeated at 2 and 4 weeks following removal of the ureteral catheter and ureteroneocystostomy and showed marked improvement in the configuration and function of the corresponding renoureteral units. CONCLUSIONS: Our experimental model fulfills the requirements for a useful model of partial ureteral obstruction, namely, simplicity, reliability, variability, and reversibility. PMID- 7771030 TI - Five-year results of a phase II study with low-dose bacille Calmette-Guerin therapy in high-risk superficial bladder cancer. AB - OBJECTIVES: Numerous studies have shown bacille Calmette-Guerin (BCG) to be an effective prophylactic and therapeutic agent for superficial transitional cell carcinoma of the bladder. The high-grade T1 lesion treated by transurethral resection alone is reported to progress to muscle invasion in 30% to 50% of the patients. Until now, optimal treatment schedule and optimal dose have not been defined. As suggested by Pagano's group, we used BCG in a lower dose than hitherto usual in our high-risk cancer patients. METHODS: Five years ago, we treated 32 Stage T1 cancer patients who were described as at high risk based on the criteria of histologic grade 3 in 21 patients, grade 2, but multiple in 11 patients, and with carcinoma in situ in 17 patients. Follow-up ranged from 51 to 63 months, with a mean of 57 months. We used BCG strain Pasteur Paris 75 mg weekly for 6 weeks and then maintenance therapy monthly for the first year and every 3 months for the second year. Complete remission was defined as negative cystoscopy, biopsy, and cytology. RESULTS: After a single 6-week course of BCG, 25 patients had negative cytology and biopsy findings after 3 months; 2 other patients needed a second 6-week cycle of BCG, for an overall response rate of 80%. Five patients underwent cystectomy because of multiple recurrences and tumor progression. After 2 years of follow-up, but under continuing maintenance therapy, 3 additional patients had tumor recurrences and also underwent cystectomy. Now, after 5 years' follow-up, the overall progression rate to cystectomy was 25% (8 of 32 patients), but none of the patients had progression to metastasis. Treatment-related toxicity did not appear to be lower at a lower dose of BCG. CONCLUSIONS: Low-dose BCG therapy is also an effective treatment in high-risk T1 bladder cancer (especially with maintenance therapy and short-term evaluations of the patients always by the same controlling physician) to prevent progression and recurrence and to preserve bladder function. PMID- 7771031 TI - Core cancer length in ultrasound-guided systematic sextant biopsies: a preoperative evaluation of prostate cancer volume. AB - OBJECTIVES: Evidence has been presented that biologic aggressiveness of prostate carcinoma increases with volume and that cancers less than 0.5 cc may be regarded as clinically insignificant for immediate treatment. We have analyzed the ability of core cancer length on needle biopsy to predict cancer volumes near the 0.5 cc threshold for distinction between incidental versus clinical carcinoma. METHODS: Systematic sextant transrectal ultrasound-guided prostate biopsies were performed on 110 men who then underwent radical prostatectomy for adenocarcinoma. The core cancer length within each biopsy was compared with the volumes of clinical and incidental carcinomas in the prostatectomy specimen. RESULTS: Among incidental (nonpalpable) cancers, 14% of those under 0.2 cc were detected, but 44% at 0.2 to 0.5 cc and 92% of those more than 0.5 cc were detected. Among clinically suspected carcinomas, 2 mm or longer core cancer length reliably predicted a cancer of 0.5 cc or larger, but among incidental cancers, it predicted a tumor of 0.2 cc or larger. A 3-mm core cancer length threshold predicted 0.5 cc for both groups. The high frequency of incidental cancers under 0.5 cc impaired the predictive value of multiple positive needle cores. Bilateral positive biopsy results indicated bilateral extension of clinical cancer in only 59% of cases. CONCLUSIONS: A core cancer length of 3 mm or more on one or two needle biopsies reliably predicts cancer of clinically significant volume (0.5 cc or larger). The high detection frequency of smaller incidental carcinomas on biopsy impairs the reliability of volume estimation from multiple positive needle cores and mandates that treatment decisions be made with knowledge of core cancer length. PMID- 7771032 TI - Intraoperative blood loss during radical retropubic prostatectomy: epidural versus general anesthesia. AB - OBJECTIVES: There are conflicting reports on the influence of different anesthetic techniques, such as regional versus general anesthesia, on intraoperative blood loss. The purpose of this study was to elucidate the effects of anesthetic technique on intraoperative blood loss in men undergoing radical retropubic prostatectomy (RRP). METHODS: One hundred patients undergoing RRP for prostate cancer were randomly assigned to receive either epidural anesthesia (EA), combined epidural and general anesthesia (EG), or general anesthesia alone (GA). Intraoperative blood loss was calculated by using a formula that accounted for the volume and hematocrit of the fluid suctioned from the surgical field, blood absorbed on surgical pads, and the patient's hematocrit. RESULTS: Mean blood loss in the EA group (1490 +/- 90 mL; mean +/- SEM) was significantly less than mean blood loss in both the EG group (1810 +/- 100 mL) and the GA group (1940 +/- 130 mL) (P = 0.01). Blood loss was not different between the EG and the GA groups (P = 0.7). Significantly less blood was transfused during surgery in the EA group (730 +/- 50 mL) compared with the EG (960 +/- 60 mL) and GA (950 +/- 70 mL) groups (P = 0.02). CONCLUSIONS: Similar blood loss in patients receiving general anesthesia, either alone or when combined with epidural anesthesia, implies that epidural anesthesia did not reduce bleeding, but, rather, that general anesthesia increased blood loss. PMID- 7771033 TI - [A morphological study of tissues in the posterior segment of the eye after modified experimental revascularization of the choroid]. AB - Morphologic examination of ocular tissues at the site of revascularization with two flaps was carried out to detect the changes in the architectonics of these flaps' vessels, vascular coating at the site of intervention, and assess the formation of relation with the vascular system of the external tissues of the eye. Experiments were carried out on the eyes of 8 cats. All the animals were subjected to local revascularization of the vascular coating with two flaps. Enucleation was carried out 1 to 6 months after the operation. The eyes were fixed in 10% neutral formalin solution, paraffin slices and blocks were prepared, stained with hematoxylin and eosin, with pyrofucin after Van Gieson, and with toluidine blue after Lison. Histologic study of ocular tissue slices 2-3 weeks after surgery showed that the flaps introduced into the supra-arachnoidal space tightly fitted each other forming a subconjunctival-episcleral transplant in which a moderate number of newly formed vessels was detected. Three to six months after surgery vascularization of the transplant proper and around it grew more and more intensive, the number of new vessels increased with their walls looking more compact; basal membrane appeared well shaped. The walls of new vessels did not differ by structure from normal vascular walls in the vascular coating. PMID- 7771034 TI - [Use of immobilized collagenase-collapor in the treatment of eye diseases]. AB - Immobilized collagenase (collapor) applied as ophthalmic medicinal films has been developed and clinically tried. A new long-acting base (aubasidan, a mucopolysaccharide of a bacterial origin), similar as the main medicinal component, collagenase, exerts a therapeutic effect. Collapor is characterized by a pronounced resolving and proteolytic action causing no appreciable side effects. Altogether 134 patients with various inflammatory and vascular diseases of the eyes were observed. An instruction for collapor application in ophthalmology is offered. PMID- 7771035 TI - [Role of immunological factors in peripheral vitreo-chorioretinal dystrophies and macular ruptures of the retina]. AB - The authors analyze the results of clinical and immunological examinations of patients with peripheral vitreo-chorioretinal dystrophies (PVCRD) and macular ruptures of the retina. No antibodies to S-AG were detected in the lacrimal fluid in 87.5% of patients with PVCRD without retinal defects. In patients with PVCRD with retinal defects antibodies to S-AG were detected in 70% of cases. These antibodies were absent in the patients with macular ruptures of the retina. In none of the patients were these antibodies detected in the blood serum. The levels of circulating immune complexes were normal in the patients PVCRD and increased in those with macular ruptures of the retina. These data permit a hypothesis on the development of local autoimmune reactions in PVCRD patients in response to the appearance of AG of the injured tissues. PMID- 7771036 TI - [Dynamic rigidometry]. AB - A new method for assessment of the rigidity of corneoscleral membrane is offered: dynamic rigidometry permitting assessment of the real rigidity of the sclera (Eo). The studies were carried out in 106 normal subjects and 154 patients with glaucoma. In normal controls Eo coefficient was 0.0044 +/- 0.0008 on an average, whereas in glaucoma patients it was two times higher (0.0109 +/- 0.0018). This coefficient virtually did not depend on the level of intraocular pressure. A relationship between Eo and glaucoma stage was detected. PMID- 7771037 TI - [State of accommodation depending on age of emmetropic and hypermetropic subjects engaged in diamond sorting]. AB - Accommodation was studied in 449 diamond sorters aged 17 to 51 engaged in this work for 1 to 34 years with emmetropic and hypermetropic refraction. Questionnaires helped detect subjects who had no complaints of vision (group A) and those with asthenopia complaints (group B). In both groups, in emmetropic and hypermetropic subjects, the furthest point of clear vision was converging the eye by 1.96 +/- 0.04 diopters on an average, that is, there was pseudomyopia. In hypermetropic subjects with occupational ophthalmopathy the nearest point is withdrawn starting from the age of 31-35 till it merges with the furthest point in subjects over 45, that is, the accommodation volume becomes nearly nuel. The results of this study contradict the assumption existing in ophthalmology about an earlier onset of presbyopia in hypermetropia than in other types of refraction. Early correction of near vision is connected with superimposition of accommodation deterioration in ametropia. It is recommended to carry out rehabilitative measure as soon as the first asthenopia signs manifest; these measures should be aimed at weakening of refraction by the site of the furthest clear vision point. In subjects aged 31-35 with occupational ophthalmopathy refraction by the nearest clear vision point should be enhanced if possible. PMID- 7771038 TI - [Tactics in choosing a vascular collector and drug administration method in intra arterial infusion therapy of organs of vision]. AB - Anatomical variants of the direction and diameter of the supraorbital artery revealed by the authors and the clinical variants of the intensity and direction of periorbital bloodstream shown by doppler studies helped optimize the selection of a facial artery for inserting an infusion system for drug delivery to the vascular system of the eye. The advantages of intraarterial infusion of drugs in the system of ocular blood supply using an automated thermo-infusion dispenser vs. the traditional methods are demonstrated: no side effects on the intraocular and regional hemodynamics, purposeful delivery of drugs to the site of ocular blood supply with a simple and convenient device. This method for the choice of a collector for intraarterial infusions and the method of drug infusion were clinically tried in 2 groups of patients: with retrobulbar intoxication neuritis and partial atrophy of the optic nerve (a total of 21 patients, 23 operations for implantation of infusion system; control group consisted of 11 patients). 120 Hour infusion therapy with, alternately, trental and actovegin resulted in improvement of the vision acuity from 0.03-0.06 to 0.3-0.8 in virtually all group 1 patients. Moreover, central scotomas disappeared and the conductivity of the axial bundle of the optic nerve recovered from 28-32 to 38-40 Hz. In group 2 defects in the visual field disappeared and its peripheral borders widened. In controls no improvement of the visual function was observed. PMID- 7771039 TI - [Perfusion pressure in ocular vessels of patients with open-angle glaucoma]. AB - Perfusion pressure in ophthalmic vessels was measured by computer-aided ophthalmodynamography in health, stenoses of the internal carotid artery, and open-angle glaucoma. A total of 70 subjects were examined. Stenoses of the internal carotid artery are associated with a noticeable reduction of perfusion pressure on the side of stenosis. Some patients develop optic nerve atrophy (without excavation). Secondary neovascular glaucoma was diagnosed in 1 patient. Primary open-angle glaucoma was revealed in none of the patients. Increase of intraocular pressure in patients with open-angle glaucoma was associated with a reduction of perfusion pressure. However, in more than 50% of patients a higher pressure was observed in the orbital artery corresponding to the eye with a higher ophthalmic tone than in the contralateral eye. This was conducive to a certain leveling of perfusion pressure. Such a reaction is regarded as a manifestation of autoregulation of ocular vessels, important for blood delivery to the eyes. PMID- 7771040 TI - [Tissue micro-diastasis and closed micro-cavities of the surgical zone in glaucoma surgery]. AB - Investigation of methods of antiglaucoma surgery in order to control the cicatrization of filtration routes of intraocular fluid discharge is carried out at the Vladivostok Medical Institute since 1989. A total of 662 operations are analyzed, which were carried out using an original method with "inverted trapezium"-shaped dissection of the deep tissues of the sclera. A microsurgical knife designed by the authors and patented was used. The results of operations indicate their sufficiently high hypotensive effect and a low incidence of complications. The authors claim that several filtering components are advisable in antiglaucoma surgery. Simplification of the technique of antiglaucoma operation, based on the concept of micro-diastasis and micro-cavities, deserves to be further researched. PMID- 7771041 TI - [Results of intraocular pharmaco-physical therapy in inflammatory diseases of the cornea]. PMID- 7771042 TI - [Results of the treatment of congenital ptosis in children using the Friedenwald Guyton method]. AB - Results of 28 surgeries for congenital ptosis after Friedenwald-Guyton's method modified by V.L. Mikheyev are analyzed. A thick woven dacron thread was used for suturing. Good results were attained in 24 cases: the pupil area was covered with the upper lid by not more than 1/5. No effect was attained in 4 cases. Cases of ineffective surgeries are analyzed. A conclusion is made that the aforesaid surgery is simple, low traumatic, and sufficiently effective. Dacron thread may be effectively used for suturing. PMID- 7771043 TI - [Characteristics of the course of phlegmon of the lacrimal sac in newborn infants]. AB - The authors describe an uncommonly stubborn course of a phlegmon of the lacrimal sac in two newborns, developing after latent ethmoiditis. They emphasize the necessity of a timely consultation of a qualified ENT specialist to plan the rational treatment strategy in such patients. PMID- 7771044 TI - [Let's recollect their names. The collaboration of V. P. Filatov and A. M. Shcherbina (archival materials)]. PMID- 7771045 TI - [Causes of insufficient effectiveness of collagen plasty (an experimental study)]. AB - Morphological and biomechanical features of the sclera after collagen plasty were studied in 90 eyes of 45 chinchilla rabbits. A reduction of the viscous elastic properties of the sclera 1 month after surgery was revealed, not described previously. The data on the changed mechanical characteristics of the sclera following collagen plasty are confirmed by the results of optic and electron microscopy; these data permit us to propose that the sclera in the immediate postoperative period (less than 1 month after the operation) represents a somewhat chaotic structure at the stage of active restructuring. Rational postoperative management of patients after collagen plasty is recommended. PMID- 7771046 TI - [A new method of formation of chorioretinal adhesions in retinal detachment]. AB - A method of intrascleral transplantation of foam gel providing the creation of stable chorioretinal adhesion at the site of the retinal defect has been experimentally developed and clinically tried. A special injector has been designed for the realization of the method, permitting stratification of the scleral capsule at a given depth. The suggested method is recommended for practical use in patients with rheumatogenic detachment of the retina in the initial and moderate degrees of vitreoretinal proliferation. PMID- 7771047 TI - [Acute retinal necrosis syndrome: diagnosis and treatment strategy]. AB - The authors describe the clinical picture, diagnostic criteria, and treatment strategy in patients with the syndrome of acute retinal necrosis, based on their own findings and published data. The syndrome of acute retinal necrosis is binocular, the difference in the time of involvement of the paired eye varying from 3 weeks to 18 months; the course of the disease is extremely severe. Starting as acute iridocyclitis, the disease rapidly progresses and leads to the development of vaso-occlusive necrotic retinitis, eventuating in retinal tissue degradation at the site of involvement, formation of ruptures and detachment of the retina. Detachment of the retina developing during its acute necrosis is associated with a drastic hypotension and rapid proliferative changes in the retina and vitreous body with the formation of numerous "dense" epiretinal membranes and funnel-shaped detachment of the retina. Active treatment strategy is recommended: emergency surgical intervention aimed at blocking of necrosis sites and ruptures of the retina. Such an approach helped attain adherence of the retina and stabilize the course of the disease. Prolonged conservative therapy of this syndrome is ineffective. PMID- 7771048 TI - Spontaneous equine pulmonary granular cell tumors: morphologic, histochemical, and immunohistochemical characterization. AB - Spontaneous equine pulmonary granular cell tumors were diagnosed in six mature horses at slaughter. These tumors were grossly recognized as multiple (5/6) or single (1/6) creamy white, firm nodules. The tumors, located adjacent to bronchi and bronchioles, often invaded airways, resulting in partial to complete occlusion of the lumina. Neoplastic cells were rounded to polyhedral with numerous eosinophilic cytoplasmic granules that reacted uniformly positive with S 100 and neuron-specific enolase antibodies and multifocally with glial fibrillary acidic protein antibodies. These cells were negative for muscle-specific actin, lysozyme, cytokeratin, chromogranin A, and myelin basic protein antigens and did not stain with silver by the Grimelius technique. Uniformly blue-green and scattered pink intracytoplasmic granules were evident with luxol fast blue and periodic acid-Schiff counterstain for myelin and myelin breakdown products. Histochemical and immunohistochemical staining results of these tumors suggest that they are composed primarily of myelinating Schwann cells with lesser numbers of scattered nonmyelinating Schwann cells. The morphologic features of the equine pulmonary granular cell tumors are strikingly similar to those of endobronchial granular cell tumors of human beings. PMID- 7771049 TI - Demonstration of Mycoplasma hyorhinis as a possible primary pathogen for porcine otitis media. AB - A study of the pathology of the ear was performed on 479 pigs ranging in age from 1 day to 1 year. Histologically, 364 (76.0%) of 479 pigs were affected with otitis. Eustachitis was the most common and preceded an inflammation of other sites of the ear, and an acute eustachitis occurred from as early as 1 week of life. Immunohistochemical examination of frozen cryostat sections revealed Mycoplasma hyorhinis (Mhr) antigens on the luminal surface of the eustachian epithelia in 14 (50.0%) of 28 piglets examined. All the pigs positive for Mhr had an acute eustachitis. Ultrastructural examination on the auditory tubes with positive immunostaining disclosed many mycoplasmas among the cilia. Mhr was isolated from the auditory tubes and tympanic cavities of 19 (67.9%) and 16 (57.1%) of 28 piglets examined, respectively. Porcine otitis media may be caused primarily by Mhr infection in the auditory tube. PMID- 7771050 TI - Clinical pathology and hemostatic abnormalities in experimental African horsesickness. AB - Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness. PMID- 7771051 TI - Feline endomyocarditis and left ventricular endocardial fibrosis. AB - A retrospective study was conducted of all feline necropsies over a 7-year period. Of a total of 1,472 necropsies, 37 cases of endomyocarditis (EMC) and 25 cases of left ventricular endocardial fibrosis (LVEF) (previously called restrictive or intermediate cardiomyopathy) were identified. There was a subset of four cats with EMC that had histologic features of both diseases. Interstitial pneumonia was seen in 25 of 35 cats (71%) with EMC but in only seven of 25 cats (28%) with LVEF. Thrombi or thromboemboli were seen in 14 of 25 cats (56%) with LVEF but in only six of 37 of cats (16%) with EMC. In both LVEF and EMC, thromboemboli were located in the abdominal aorta, left atrium and ventricle of the heart, femoral artery, cranial mesenteric artery, liver, pulmonary artery, jugular vein, or a meningeal vessel. Each cat had a single thrombus/thromboembolus, except for four cats with LVEF that had more than one. The histologic and clinical findings suggest that EMC and LVEF represent temporally different manifestations of a single disease entity. PMID- 7771052 TI - Murine cytomegalovirus-associated arteritis. AB - Unique inflammatory lesions affecting the ascending aorta and pulmonary artery of BALB/c and C57BL/6 mice infected with murine cytomegalovirus (MCMV) were identified in a pilot and two subsequent experiments to characterize the potential effect of MCMV infection on diet-induced atherosclerotic lesions. Suckling BALB/c and C57BL/6 mice were inoculated with MCMV and subsequently fed either a commercial mouse diet or a synthetic atherogenic diet from weaning. The three experiments varied with respect to the age of the mice at the time of MCMV inoculation and the dose of virus given. The conditions of MCMV exposure were progressively modified in the three experiments to increase the prevalence of MCMV-associated inflammatory lesions in the pulmonary artery and aorta. In the final experiment, in which suckling mice were inoculated at 9 days of age, MCMV associated arteritic lesions had an observed prevalence at 8 weeks post inoculation of 87.5% (7/8) in BALB/c mice on the normal diet and 100% (8/8) in C57BL/6 mice on the normal diet and in both strains on the atherogenic diet. The inflammatory lesions in both vessels were characterized by mononuclear cell infiltrates containing CD3+, CD4+, and CD8+ lymphocytes. The cellular infiltrates were often more intense on the adventitial surface and infiltrated into the overlying tunica media. The intima was infiltrated by mononuclear cell infiltrates that appeared to contain more macrophages and fewer lymphocytes than did the adventitial infiltrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771053 TI - Higher incidence of Gastrospirillum sp. in swine with gastric ulcer of the pars oesophagea. AB - Gastric ulcer in swine is characterized by an area of acid-peptic digestion, occurs usually in the pars oesophagea of the stomach, and has unknown etiopathogenesis. The present work was carried out to investigate the prevalence of the newly described spiral-shaped microorganism Gastrospirillum sp. ("Gastrospirillum suis") in stomachs of abattoir pigs with and without gastric ulcer. Stomachs were removed from 32 consecutive pigs presenting apparently normal mucosa and from 32 additional consecutive pigs presenting frank, chronic gastric ulcer of the pars oesophagea. Fragments of antral, oxyntic, cardiac and pars oesophagea regions were taken from each stomach and processed for histology and for identification of Gastrospirillum sp. in tissue sections. The microorganisms were identified mainly in the mucous layer and in gastric foveolas of the antral and oxyntic mucosa. Forty pigs (62.5%) were positive for Gastrospirillum sp.; among them, 27 (67.5%) had gastric ulcer, and 13 (32.5%) had no ulcer. Twenty-four pigs (37.5%) were negative for Gastrospirillum sp.; among them, five (20.8%) presented with gastric ulcer, and 19 (79.2%) had no ulcer. There was a significant difference between pigs with and without gastric ulcer in regard to the presence of Gastrospirillum sp. (P < 0.01). The spiral-shaped microorganism Gastrospirillum sp. that inhabits the stomach of pigs should be considered a possible factor connected with the etiopathogenesis of swine gastric ulcer. PMID- 7771054 TI - Lectin histochemistry of normal and herpesvirus-infected bovine nasal mucosa. AB - Proliferation of Pasteurella haemolytica serotype 1 in the nasal cavity following stress or viral infection is an important event in the pathogenesis of bovine pneumonic pasteurellosis. Enhanced adhesion of P. haemolytica to nasal mucosa could be one factor that predisposes animals to this proliferation. Nasal mucosa from normal and bovine herpesvirus-1 (BHV1)-infected cattle were examined histochemically for their glycoconjugate composition. Twenty lectins were screened, six of which were chosen for subsequent study. Three of these were specific for N-acetylgalactosamine (NAGal) (Dolichos biflorus, Glycine max, and Vicia villosa), and one each was specific for N-acetylgalactosamine/galactose (Griffonia simplicifolia-I), mannose/glucose (Canavalia ensiformis), and N acetylglucosamine (Triticum vulgaris). For the surface mucosa and submucosal glands, there was greater reactivity in samples from BHV1-infected than from normal cattle for all six lectins. Reactivity was most prominent for the NAGal specific lectins. Neuraminidase treatment of samples from normal and BHV1 infected cattle tended to result in greater lectin reactivity. Lectin reactivity was generally more intense in focally inflamed areas, but diffuse reactivity was not substantially affected by inflammation. BHV1-induced alteration of nasal mucosal glycoconjugates could enhance adhesion and colonization of P. haemolytica to nasal surfaces and may be one factor responsible for the increased number of P. haemolytica serotype 1 in the nasal cavity following viral infection. PMID- 7771055 TI - Immunoreactivity of canine epithelial and nonepithelial neoplasms with monoclonal antibody B72.3. AB - Monoclonal antibody (MAb) B72.3, which binds to a human tumor-associated glycoprotein termed TAG-72, was applied to a wide range of epithelial and nonepithelial neoplasms from dogs. Immunoreactivity was detected by the use of an avidin-biotin complex (ABC) immunoperoxidase method. A variety of epithelial neoplasms, but none of the nonepithelial neoplasms, were positive (> or = 5% staining) for MAb B72.3. MAb B72.3 stained 100% (4/4) of gastric, 100% (6/6) of intestinal, 50% (2/4) of pancreatic, and 80% (4/5) of rectal adenocarcinomas but only 20% (1/5) of squamous cell carcinomas and 20% (1/5) of complex tubular mammary gland adenocarcinomas. None of the hepatocellular carcinomas and perianal and sebaceous gland adenocarcinomas stained. Most types of benign epithelial neoplasms did not stain, except for 75% (6/8) of rectal adenomas and 25% (1/4) of squamous cell papillomas. Normal gastrointestinal mucosa adjacent to and entrapped in neoplasms did stain with MAb B72.3. None of the benign and malignant nonepithelial neoplasms of mesenchymal, neuroendocrine, or lymphohematopoietic tissue origin stained. The results of this study demonstrate that MAb B72.3 has selective immunoreactivity for adenocarcinomas, especially those arising from the digestive tract; however, limited immunoreactivity was observed for other types of carcinomas and benign epithelial neoplasms and for normal gastrointestinal mucosa in the dog. PMID- 7771056 TI - Immunoreactivity of canine transitional cell carcinoma of the urinary bladder with monoclonal antibodies to tumor-associated glycoprotein 72. AB - Tumor-associated glycoprotein 72 (TAG-72) is a large, high molecular weight, mucinlike antigen that is expressed in a wide variety of human carcinomas. Three different TAG-72 monoclonal antibodies (MAbs), designated B72.3, CC49, and CC83, were applied to the following archived samples from the dog: 1) 51 transitional cell carcinomas of the urinary bladder, 2) 15 hyperplastic/inflamed urinary bladders, and 3) eight normal urinary bladders. Immunoreactivity was detected with an avidin-biotin complex immunoperoxidase method. Fifty-three percent (27/51) of transitional cell carcinomas were positive (> or = 5% staining) for MAb B72.3. MAb B72.3 staining of these transitional cell carcinomas did not statistically correlate with any of the examined features of malignancy, including histologic grade, clinical stage, DNA ploidy, or presence of vascular/lymphatic invasion. In regard to the staining of transitional cell carcinoma by the other two TAG-72 antibodies, 53% (27/51) of the samples were positive for MAb CC83 and 63% (32/51) were positive for MAb CC49. The finding that similar populations of neoplastic urothelial cells in serial sections from the same neoplasm stained with all three TAG-72 antibodies supports the hypothesis that an antigen similar to TAG-72 was expressed in canine transitional cell carcinoma. None of the normal urinary bladders nor any of the hyperplastic/inflamed urinary bladders stained with any of the three TAG-72 antibodies tested. The results of these studies demonstrated that the staining of canine transitional cell carcinoma with all three TAG-72 antibodies was specific for neoplastic urothelial cells and that an antigen similar to TAG-72 was expressed. PMID- 7771057 TI - In situ hybridization and immunohistochemical study of walleye dermal sarcoma virus (WDSV) nucleic acids and proteins in spontaneous sarcomas of adult walleyes (Stizostedion vitreum). AB - Twenty-two anatomically independent dermal sarcomas from six adult walleye fish (Stizostedion vitreum) collected during the spring from Oneida Lake, New York, were examined by in situ hybridization and immunohistochemistry for the presence of walleye dermal sarcoma virus (WDSV). The viral RNA, DNA, and 90-kd protein were localized at the cellular level. Riboprobes complementary to the 5' terminal region of WDSV genome were used to detect viral nucleic acids. Rabbit polyclonal antiserum was generated against the 90-kd virus-associated antigen, presumably a product of the env gene, for immunohistochemical studies. Viral transcripts were detected in the neoplastic cells of all dermal sarcomas, in which they were generally abundant. Rare mononuclear inflammatory cells and cells within the epidermis also expressed viral RNA. In all sarcomas, low to moderate levels of viral DNA were present in all neoplastic and most mononuclear inflammatory and epidermal cells. Many neoplastic cells were immunopositive for the virus associated protein. The distribution of immunopositive neoplastic cells mimicked approximately that of cells containing viral transcripts. The number of neoplastic cells with transcripts exceeded that of cells with protein, suggesting that productively infected neoplastic cells constituted a subset of the neoplastic cells that expressed WDSV transcripts. The viral antigen was also present within many mononuclear inflammatory cells. These data suggested that 1) dermal sarcomas were associated with elevated transcriptional activity of WDSV in the neoplastic cells and 2) the cell tropism of WDSV extended beyond the mesenchymal fibroblast-like neoplastic cells and included at least mononuclear inflammatory and epidermal cells. PMID- 7771058 TI - Pasteurella haemolytica lipopolysaccharide-induced cytotoxicity in bovine pulmonary artery endothelial monolayers: inhibition by indomethacin. AB - Exposure of bovine pulmonary artery endothelial cells to Pasteurella haemolytica lipopolysaccharide caused severe morphologic changes. Initially, there was dilatation of the rough endoplasmic reticulum and mitochondrial swelling followed by cell retraction, membrane bleb formation, and cell detachment. The affected endothelial cells had severe membrane damage resulting in the leakage of lactate dehydrogenase. Indomethacin in concentrations of 0.5 mM or greater caused marked decreases in the lipopolysaccharide-induced leakage of lactate dehydrogenase. Indomethacin at 5 mM also caused a marked reduction of the lipopolysaccharide induced morphologic changes resulting in apparent maintenance of the monolayer integrity for 8 hours versus 1 hour in the lipopolysaccharide-treated control. A marked decrease in the cell and nuclear membrane effects resulted, but the rough endoplasmic reticulum dilatation and mitochondrial changes proceeded. These results indicate that indomethacin does not prevent lipopolysaccharide binding but interferes with later events in lipopolysaccharide-induced cytotoxicity in the bovine pulmonary endothelial cell. The concentration of indomethacin required to produce this inhibition suggests that the primary mechanism is not cyclooxygenase inhibition. PMID- 7771059 TI - Early development of encephalomyocarditis (EMC) virus-induced orchitis in Syrian hamsters. AB - Lesions associated with encephalomyocarditis (EMC) virus in the testes of Syrian hamsters were investigated. Histopathologic changes were first detectable by light microscopy at 3 days postinoculation (DPI). Immunohistochemically, virus antigens were detected in the cytoplasm of germ cells and Sertoli cells in some seminiferous tubules beginning at 2 DPI. The following ultrastructural changes were observed: 1) swelling of mitochondria and dilatation of endoplasmic reticulum in germ cells, 2) large number of residual bodies in seminiferous tubules, 3) aggregates of virus-like particles in the cytoplasm of degenerated cells and tubular lumen, 4) condensation of cytoplasm and dilatation of endoplasmic reticulum in Sertoli cells, and 5) degenerative changes in capillary endothelial cells. PMID- 7771060 TI - Symmetric bilateral brachymetacarpalia of a dog. AB - Malformations of the canine manus are infrequently cited in the literature but include polydactylia and syndactylia. Here, a case of brachymetacarpalia affecting the second and fifth metacarpal bones of both forelimbs of a mixed breed dog is described. The initial impression of shortened digits was disproved by statistical comparison with normal skeletons, but the presence of shortened metacarpal bones was demonstrated. Other malformations of the manus and appropriate terminology are briefly discussed. PMID- 7771061 TI - Intracranial gangliocytoma in a dog. AB - The clinical, pathologic, immunohistochemical, and electron microscopic characteristics of a pure intracranial gangliocytoma in a 6-year-old spayed female dog are presented. The tumor is very rare in humans, and has not been previously reported in the dog. The most remarkable feature of this tumor was that it was composed of a single neuronal cell type without the presence of glial elements, as demonstrated by the negative immunohistochemical reaction to glial fibrillary acidic protein. PMID- 7771062 TI - Rapid diagnosis of Listeria monocytogenes by immunohistochemistry in formalin fixed brain tissue. PMID- 7771063 TI - Assignment of islet amyloid polypeptide (IAPP) gene to feline chromosome B4 using the polymerase chain reaction technique on feline-rodent hybrid cell lines. AB - The most characteristic morphologic features of the pancreatic islets of human non-insulin-dependent diabetes mellitus (NIDDM, or type 2 diabetes mellitus) and of similar forms of diabetes in cats and macaques are the deposition of amyloid (islet amyloid) and the loss of beta cells. Islet amyloid is derived from islet amyloid polypeptide (IAPP), which is a normal secretory product of the beta cells. Therefore, knowledge of the IAPP gene is of potential importance in defining the pathogenesis of NIDDM. To identify the feline chromosome(s) on which the IAPP gene is located, we screened genomic DNA obtained from 38 feline-rodent hybrid cell lines that have a known feline chromosome content. Feline IAPP DNA was amplified and detected using the polymerase chain reaction technique. Discordancy analysis for each feline chromosome showed that chromosome B4 had the lowest discordancy (P < 0.0001). Feline chromosome B4 shows an extensive conserved syntenic relationship with human chromosome 12, on which the human IAPP gene is located. This study therefore extends and confirms the homology between human chromosome 12 and feline chromosome B4 and provides an additional genetic marker for feline chromosome B4. PMID- 7771064 TI - Giant cell glioblastoma in the frontal cortex of a dog. AB - A dark gray mass 3 cm in diameter replacing the right frontal cortex was found in the brain of a 5-year-old male Doberman Pinscher dog at necropsy. Microscopic studies revealed that the mass consisted of a proliferation of pleomorphic tumor cells: large bizarre or plump eosinophilic cells, multinucleated giant cells, and small lymphocytic cells. These neoplastic cells at the margin of the necrotic area had a psuedopalisade arrangement and tended to proliferate around blood vessels. Immunohistochemically, the tumor cells reacted intensely with the antibody for vimentin and moderately with those for S-100 and glial fibrillary acidic protein. This canine tumor is placed in the category of glioblastoma or undifferentiated astrocytoma, which is analogous to human giant cell glioblastoma. PMID- 7771065 TI - Immunohistochemical identification of porcine reproductive and respiratory syndrome virus (PRRSV) antigen in the heart and lymphoid system of three-week-old colostrum-deprived pigs. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) antigens were detected by a streptavidin-biotin complex technique in tissues of 3-week-old colostrum-deprived pigs that had been inoculated intranasally with PRRSV and had developed moderate respiratory disease. Moderate, multifocal, tan-colored consolidation of the lungs and severe enlargement of the lymph nodes were noted at necropsy. Severe interstitial pneumonia characterized by type 2 pneumocyte proliferation, septal infiltration with mononuclear cells, and accumulation of macrophages and necrotic cells in alveolar spaces was observed at 4 and 9 days postinoculation. Moderate multifocal perivascular lymphohistiocytic myocarditis was observed at 9 days postinoculation. Marked lymphoid follicular hyperplasia and follicular necrosis in the tonsil, spleen, and lymph nodes was observed. A monoclonal antibody that recognizes a conserved epitope of PRRSV nucleocapsid protein was used as primary antibody for immunohistochemistry. Antigen was readily detected in alveolar macrophages in the lung and in endothelial cells and macrophages in the heart. Macrophages and cells resembling dendritic cells in tonsil, lymph nodes, thymus, and spleen also stained intensely positive for viral antigen. PRRSV appears to replicate primarily within macrophages in the respiratory and lymphoid systems of the pig. PMID- 7771067 TI - Pathologic lesions: they're the worst kind. PMID- 7771066 TI - Spontaneous osteosarcoma of the meninges in an albino rat. AB - A search of the rat tumor literature revealed no papers on naturally occurring primary osteosarcoma of meninges. In humans, this tumor, arising primarily from the meninges, is unusual; only two cases have been reported. We report on a spontaneously occurring osteosarcoma arising from meninges in a 2-year-old female albino rat. The diagnosis was made on the basis of gross, microscopic, and ultrastructural findings. The diagnosis of this neoplasm is supported by the fact that a primitive mesenchymal cell in the meninges is capable of giving rise to a wide variety of neoplasms. PMID- 7771068 TI - Tumors in St. Lawrence beluga whales (Delphinapterus leucas) PMID- 7771069 TI - More about carcinogens and tumors. PMID- 7771070 TI - Clinical and epidemiological correlates of the neurohistology of cases of histologically unconfirmed, clinically suspect bovine spongiform encephalopathy. AB - The associations between three major categories of the neurohistological diagnoses and the epidemiological data were examined in unconfirmed cases of clinically suspect bovine spongiform encephalopathy (BSE). The diagnostic categories were focal spongiosis of white matter (37 cases), encephalic listeriosis (13 cases) and no significant lesions (78 cases). An additional control category of 200 confirmed cases of BSE were included for comparison. Epidemiological variables were the frequencies of specific clinical signs, the season of clinical onset, the age, the duration of the clinical signs and the geographical origin of the cases. Discriminant analysis was used to assess the contribution of these variables to the distinction between the diagnostic categories. The analyses characterised the cases of listeriosis by their shortest clinical duration, the greater prevalences of certain clinical signs and their occurrence mainly in winter and spring, consistent with current understanding of the disease. Cases of focal spongiosis, a lesion of unknown significance, but potentially with a metabolic causation, were tentatively separable from cases with no significant lesions by their winter onset. The results also confirmed that among the categories, the cases of BSE had the longest clinical duration. Despite their statistical significance, the findings do not have sufficient predictive power to be of value in making clinical decisions. PMID- 7771072 TI - Clinical and pathological changes associated with atoxoplasma in a captive bullfinch (Pyrrhula pyrrhula). PMID- 7771071 TI - Severe post-dipping dermatitis and subcutaneous fluid swellings associated with two outbreaks of sheep scab (Psoroptes ovis infestation) AB - Large subcutaneous fluid swellings developed on some of the sheep in two flocks infested with Psoroptes ovis during the two weeks after they had been plunge dipped in phenol-based solutions. The swellings contained between 1 and 10 litres of exudate and affected 4 per cent of the sheep in each flock. The sheep with subcutaneous fluid swellings or exudative dermatitis had significantly lower serum albumin concentrations than the unaffected sheep (P < 0.05). In most cases secondary bacterial infections of the exudate occurred and these necessitated intensive antibiotic therapy. The severity of the skin lesions posed a serious welfare problem. PMID- 7771073 TI - Primary transmissible venereal tumour in the nasal cavity of a dog. PMID- 7771075 TI - New rules on medicines. PMID- 7771074 TI - Persistent efficacy of moxidectin against Dictyocaulus viviparus and Ostertagia ostertagi in cattle. PMID- 7771076 TI - New rules on medicines. PMID- 7771077 TI - New rules on medicines. PMID- 7771078 TI - New rules on medicines. PMID- 7771079 TI - New rules on medicines. PMID- 7771080 TI - Hydatid disease. PMID- 7771081 TI - [Antioxidant activity of natural and synthetic quinones]. AB - Antioxidation activity (AOA) of ubiquinone (Q10), phylloquinone (vitamin K1), menadione as well as of the newly synthesized analogues of vitamin K1--N derivatives of 2-methyl-3-aminomethyl 1.4-naphthoquinone, producing autocomplexes with intramolecular transfer of electrons, was studied in the model system of the methyl oleate initiated oxidation. The menadione AOA was shown to be 2-fold higher as compared with the inhibitory activity of natural quinones. Activity of AK-40 and AK-49, artificial analogues of vitamin K1, was higher 2.6-fold than that of ubiquinone and phylloquinone and 1.4-fold higher than menadione activity. At the same time, AOA of ubiquinone and phylloquinone was 1.5-fold lower than the tocopherol activity, while naphthoquinones AK-40 and AK-49 were 2-fold more active as compared with tocopherol but their activity was 2-fold lower than ionol. Mechanism of natural and synthetic quinones action as well as properties of their long chain analogues are discussed. PMID- 7771082 TI - [Structure and function of lipoproteins from the aspect of protein biochemistry (hypothesis)]. PMID- 7771083 TI - [Biochemical bases for the antiseizure role of the pineal gland]. AB - Metabolism of serotonin was studied in pineal gland of Wistar rats with low and high rate of audio excitability as well as in the Krushinsky-Molodkina rat population genetically predisposed to audio-dependent convulsions. Intensive turnover of serotonin via N-acetyl serotonin into melatonin was found in pineal gland of rats insensitive to sensory stimulus, whereas the rate of this response was decreased in the gland tissue of animals sensitive to audio effects as well as inhibition of serotonin turnover into melatonin was noticed in pineal gland of rats predisposed genetically to audio-dependent convulsions. PMID- 7771085 TI - [The effect of neuroleptics on blood proteins during development of toxic cerebral edema-brain swelling]. AB - Simulation of toxic brain edema-swelling allowed one to analyze the dynamics of blood protein alteration in presence of various neuroleptics. Alterations in blood protein fractions correlated with dynamics of nervous tissue impairments. All the drugs studied exhibited similar antiswelling action involving the gamma globulin sub-system activation. At the same time, the neuroleptics with activating and depriving effects demonstrated an oppositely directed influence on blood albumins. PMID- 7771084 TI - [Oxidative modification of human serum proteins. A method of determining it]. AB - A rate of protein oxidative destruction may be estimated from the reaction of the resultant carbonyl derivatives of amino acids reaction with 2,4-dinitrophenyl hydrazine. The procedure for estimation of 2,4-dinitrophenyl hydrazones was modified for clinical application. The initiating effect of nonenzymatic components (Fe(3+)-ascorbic acid, Fe(2+)-O2, Fe(2+)-H2O2) was in the metal catalyzing oxidation of proteins. Estimation of derivatives of 2,4-dinitrophenyl hydrazones in tissues may serve as a pattern of protein oxidative modification during oxidative stress in the body. PMID- 7771086 TI - [The role of proteins in the immunomodulating effect of bioginseng products]. AB - Immunomodulating properties of the bioginseng preparations (Panax ginseng), isolated from the cell culture of ginseng calluses, were studied in model experiments of acquired immunodeficiency developed as a result of long-term protein starvation or after vinblastin administration. The following preparations were studied: 1) preparation obtained by means of the cell culture cryoconcentration, 2) ethanol extract of the cell culture, 3) high-molecular protein containing fraction of the bioginseng I. Under conditions of acquired immunodeficiency all the preparations studied were shown to increase the content of antibody producing cells developed in response to sheep erythrocytes administration, while the highest effect exhibited the bioginseng preparation III. These data suggest that proteins are of great importance in the immunomodulating effects of bioginseng preparations. PMID- 7771087 TI - [Antioxidant effect of a Ural licorice product in acute impairment of pulmonary surfactant by total gamma irradiation]. AB - Total single irradiation of rats at a dose of 2 Gy caused activation of lipid peroxidation in lung surfactant and blood serum within 7 days. Most pronounced alterations occurred in content of 2-thiobarbituric acid-positive substances and in activity of the antioxidant system enzymes. Administration of the preparation isolated from Liquorice uraliensis within 2 weeks before the irradiation and within 7 days after the treatment contributed to inhibition of the radiation induced lipid peroxidation. PMID- 7771088 TI - [An enterosorbent with trimethylaminoethanol chloride. 2. Hypolipidemic action and effect on cholesterol absorption in the intestine (experimental data)]. AB - Enterosorbent containing trimethyl aminoethanol chloride administered per os into rabbits accelerated the rate of experimental hypercholesterolemia regression. Moreover, this substance decreased 4-14C-cholesterol absorption in the rat intestine. PMID- 7771089 TI - [Correcting effect of nicotinamide on hemoglobin glycosylation in streptozotocin diabetes in rats]. AB - Streptozotocin induced diabetes in rats was accompanied by development of hyperglycemia, by increase in the rate of hemoglobin and albumin glycosylation in blood and by elevation of 2,3-diphosphoglycerate content in erythrocytes. Alterations of the dissociation properties and the decrease in Hb P50 value suggested the reduced affinity of hemoglobin to oxygen. Injection of nicotinamide, which is involved in NAD+ biosynthesis, caused a decrease of glucose content in blood, stabilized the content of 2,3-diphosphoglycerate and of glycosylated hemoglobin in erythrocytes. Nicotinamide appears to decrease the rate of hemoglobin glycosylation and enhanced the tissue oxygen utilization under hypoxic conditions. PMID- 7771090 TI - [Expression of lysosomal enzymes in pregnancy]. AB - Activities of 6 lysosomal enzymes in leukocytes and 3 enzymes in blood serum were studied in pregnant women. Only activity of beta-D-glucosidase was not altered within all the pregnancy of I-III trimesters, while activity of all the other enzymes studied was distinctly increased to the third trimester. Use of the data obtained in prenatal diagnosis of lysosomal storage diseases is discussed. PMID- 7771091 TI - [Effect of carnosine and its derivatives on ADP-induced human platelet aggregation]. AB - ADP-induced aggregation of thrombocytes was studied in patients with cerebrovascular impairments as well as after treatment with carnosine and its native derivatives; these drugs proved to be modulators of the cell aggregation. Carnosine decreased the rate of thrombocyte aggregation in patients with high index of aggregation and exhibited the proaggregation activity in patients with low rate of aggregation. The antiaggregation activity of the preparations studied, used at physiological concentrations 3.5 mM, was increased as follows: carnosine (17%) < histidine < acetyl anserine < ophidine < anserine (35%). Application of carnosine and its native derivatives may be promising and effective in correction of thrombocyte functional properties in patients with cerebrovascular impairments. PMID- 7771092 TI - [Level of lipid-bound sialic acids in blood from brain tumor patients]. AB - Content of lipid-bound sialic acids was studied in blood serum of patients with benign tumors--gliomas, neurinomas, meningiomas, with malignant tumors--gliomas and anaplasia, glioblastomas, sarcoma, as well as of patients with impairment of peripheral nervous system (without any tumors) and of healthy volunteers. Content of lipid-bound sialic acids in blood serum of patients with benign tumors was similar to that of controls, while it was distinctly increased in all the patients with malignant tumors. These results corresponded to literature data, where the patients with non-brain localization of tumors are considered. PMID- 7771093 TI - [Status of the antioxidant enzyme system in benign symmetrical lipomatosis and changes in it from the use of antioxidant therapy]. AB - Activity of the antioxidation enzymatic system, involving evaluation of glutathione-reductase, -peroxidase and -S-transferase as well as glucose-6 phosphate dehydrogenase activities, was studied in blood plasma, leukocytes, lymphocytes and erythrocytes of patients with benign symmetric lipomatosis. Elevation in the rate of lipid peroxidation induced the antioxidation enzymatic system and caused a imbalance of its individual units. Intensive antioxidation therapy using "Aevit" allowed correction of the imbalance observed in the enzymatic activity. PMID- 7771094 TI - [Dynamics of the level of plasma myoglobin in oncology patients with and without complications in the postoperative period]. AB - Initial hypermyoglobinemia was found in patients with cancer of lungs, large intestine and rectum. Within early postoperational period under favourable conditions moderate increase in content of free myoglobin was detected, most pronounced in patients with lung cancer. Maximum concentration of myoglobin was estimated within first postoperational day, normalization occurred within 3-4 days after the operation. In patients with postoperational complications (peritonitis, pneumonia, sepsis, etc) increase in content of myoglobin was more distinct (1.6-2-fold) and was maintained within the longer period. Increase in content of blood plasma myoglobin occurred usually before manifestations of clinical symptoms related to postoperational complications. PMID- 7771095 TI - [Refining criteria for supplying the body with vitamin C]. AB - As shown by mathematical analysis of a dependence of vitamin C excretion with urine on its content in blood as well as by plotting and mathematical interpretation of the variation curves exhibiting distribution of the ascorbic acid detected in blood plasma of persons additionally treated with vitamin C, the values 0.4-0.5 mg/dl of vitamin C (lower limit of normal values) may be recommended as a criterion of the vitamin normal consumption which corresponded to literature data. The value 0.7 mg/dl used in literature is the optimum content of vitamin C in blood. Excretion of vitamin C with urine, corresponding to lower limits of the vitamin consumption, constituted 0.4 mg/h in adults and 0.2 mg/h-in children of 5-14 years old. Metabolism of vitamin C in patients with diabetes mellitus was considerably distinct from that of healthy persons. As a criterion of normal vitamin C consumption in children of 9-13 years old impaired with diabetes mellitus, the content 1 mg/dl of vitamin C in blood plasma should be considered and its excretion with urine--more than 1.8 mg/h. PMID- 7771096 TI - [A micromethod for determining tissue lipase activity using gas-liquid chromatography]. AB - Lipase activity was studied in preparations of skeletal muscles and fatty tissue by means of measurement of oleic acid methyl ester concentration developed after triolein hydrolysis using gas-liquid chromatography apparatus. The procedure described helped unify the methodology approaches in estimation of tissue lipases activity and of free fatty acid spectrum of blood serum in microquantities of the material studied, it exhibited high sensitivity and specificity. PMID- 7771097 TI - [The effect of covalently and noncovalently bound complexes of albumin with bilirubin on DNA and protein synthesis in liver and spleen of rats subjected to splenectomy and partial hepatectomy]. AB - Noncovalently bound complexes of albumin and bilirubin were found to stimulate DNA and protein synthesis in partially hepatectomized regenerating rat liver tissue, while the covalently bound complex inhibited both these synthesis types in liver tissue after partial hepatectomy. Splenectomy of intact rats caused an induction of DNA and protein synthesis in liver tissue but partial hepatectomy decreased drastically the synthesis rate in spleen, thus suggesting that humoral factors stimulating the proliferation response in liver and spleen tissues were developed after spleen- and hepatectomies. The covalently bound albumin and bilirubin complex did not affect the rate of DNA and protein synthesis in liver tissue of splenectomized rats, while the complex with noncovalent bonds restored the rate of DNA and protein synthesis in the spleen of rats with partial hepatectomy. Only the noncovalently bound complex of albumin and bilirubin exhibited the properties inherent in hepatotropic growing factor whereas albumin administration was not effective. Possible structure and action of the noncovalently bound albumin and bilirubin complex are discussed. PMID- 7771098 TI - [Clinical study of the effectiveness of filters in vacuum cleaners for reducing the concentration of dust mites in the household]. AB - The faeces of the dust mite are the most significant source of allergy for those allergic to the dust mite. During vacuum cleaning, faecal particles are emitted from the cleaner and into the air to form pathological concentrations. The aim of the study was to discover if these extreme concentrations could be prevented by the use of appropriate filters. As the allergen source, dust mite faeces were used. A Miele vacuum cleaner type S424i was used without filter, with S-Class filter, and with Super Air Clean Filter. In the first test 1 g, and in the second test 2 g of dust mite faecal particles were evenly spread and then vacumed up. While using each filter in turn, the expelled air was measured for faecal concentrations. The analysis was performed by counting the number of faecal particles, and determining the content of major allergen Der p I in the expelled air. Without a filter there was a massive concentration of faecal particles in the expelled air. The simple filter Type (S-class-filter) achieved a significant reduction on the emission of allergens. The more complex special filter (Super air clean filter), was able to remove all traces of allergens from the expelled air. PMID- 7771099 TI - [Kidney function and electrolyte metabolism in healthy pregnant women]. AB - In pregnant women alterations in kidney function, hormone, electrolyte and water metabolism are common findings. In 15 healthy pregnant women the kidney function and electrolyte metabolism were investigated during pregnancy and after delivery. The glomerular filtration rate measured by creatinine clearance was 20% higher in the I. trimester than in the II. and the III. trimesters and after the delivery. The sodium clearance was in the III. trimester significantly lower than in both the I. and the II. trimesters (p < 0.001, p < 0.01); the fractional sodium excretion was lowest in the third trimester. Furthermore the serum calcium concentration decreased significantly in the II. and III. trimester in comparison to the I. trimester (p < 0.01, p < 0.001), which was associated with a moderate increased urinary calcium excretion. The phosphate clearance increased during pregnancy and decreased approximately 50% after delivery (p < 0.01). The magnesium clearance was 40% higher in the third trimester in comparison to the I. trimester (p < 0.05) and 61% higher than the value post delivery (p < 0.01). The uric acid clearance during pregnancy was markedly increased and decreased 70% after delivery (p < 0.05). The results showed that in the III. trimester an intensive sodium retention occurred, which is associated with an increase of the plasma volume, interstitial fluid and body weight. The decreased serum calcium concentration in the II. and III. trimesters, the increased urinary calcium excretion as well as increased phosphate clearance suggest an increased parathyroid-hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771100 TI - [Comment on Edith Szanto, Doris Gruber, M. Sator, W. Knogler and J. C. Huber: Placebo controlled study of Melbrosia in treatment of climacteric symptoms]. PMID- 7771101 TI - [Hormone substitution with premarin plus. Results of an Austrian multicenter treatment study]. AB - Estrogen/progestin hormone replacement therapy in menopausal women has 2 important medical rationales. First of all, patients are relieved from the subjective symptoms almost fully. In addition patients benefit from prophylaxis of long term even life threatening sequelae of estrogen deficiency. This paper documents the results of a multicenter phase IV study, performed nationwide in Austria with 158 participating gynaecologists. Objective of this phase IV study was the analysis of efficacy and safety data of a new estrogen/progestin hormone replacement therapy scheme under almost practice conditions in the gynaecological context. The therapy supplied was Premarin plus, containing 28 coated tablets of 0.625 or 1.25 mg conjugated estrogens and in addition 12 tablets for the last cycle days containing 5 mg medrogeston. Thus, the dispensing gynaecologists had the option of an individual estrogen dose adjustment in case the low starting dose showed lack of efficacy. The results are based on the data of 1508 recruited female patients. A very high degree of representativeness is attributable to the high number of recruited patients. Overall judgement of the results shows a very high level of efficacy and a well tolerated scheme of hormone replacement therapy with the option of individual estrogen dose adjustments. PMID- 7771103 TI - [Clinical trials--methodological gold standard or naive reductionism?]. AB - The methodological concept of the randomized controlled clinical trial is a relatively recent invention. It is widely accepted to be the only means of conclusively establishing a cause effect relationship between a given therapeutic intervention and an observed outcome. There are, however, numerous pitfalls. Ethical concerns and/or practical problems can seriously affect both proper randomisation as well as the use of a placebo treatment as the control intervention. Sometimes blinding of the patients or the therapist may be difficult or even impossible, depending on the availability of a similar treatment without the specific therapeutic effect, whereas a satisfactory investigator blinding can be achieved in most instances. Practical problems can be minimised by adapting the trial design to the given clinical situation. The fact that a number of drawbacks exist, must, however, not be used as an argument to abstain from performing such studies--simply because there is no better alternative. PMID- 7771102 TI - [Iontophoresis in the treatment of pain]. AB - The objective has been to verify the effectiveness of iontophoresis in alleviating conditions of pain by means of a computer-assisted search of the pertinent literature. The search was performed with the aid of the Medline database (1984 bis 1993) and reference lists (studies from 1954). SELECTION CRITERIA: all clinical trials performed with at least one control group as well as all experimental studies conducted within the same period. The selection criteria were met by 10 experimental and 15 clinical studies. The studies were categorized by substance group. The following groups of substances were applied (experimentally/clinically): local anaesthetics (0/6), non steroidal anti inflammatory drugs (2/3), vinca-alkaloids (1/2), corticosteroids (3/1), morphine (0/1), iodide (4/1) and fluoride (0/1). Both short-term effects (lidocaine, procaine, flufenamic acid, morphine) and long-term effects (benzocaine salicylamide, diclofenac, Mobilat, vinca-alkaloids, dexamethasone-lidocaine, iodide, fluoride) were studied. Comparisons were made against placebo iontophoresis (lidocaine, procaine, flufenamic acid, diclofenac, Mobilat, vinca alkaloids, dexamethasone-lidocaine, morphine, fluoride), solely topical administration (procaine, benzocaine-salicylamide, flufenamic acid), placebo administration without current (procaine, flufenamic acid), and other methods (lidocaine, iodide). With one single exception (lidocaine), none of the studies included groups without treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771104 TI - P450 in the rat and man: methods of investigation, substrate specificities and relevance to cancer. AB - 1. Considerable evidence has been accumulated that orthologous rat and human P450 forms oxidize numerous chemicals in a highly similar manner, including the detoxication and activation of mutagens and carcinogens. 2. Nevertheless, certain specific substrates of rat P450s are not so well oxidized by the orthologous human forms, and vice versa. 3. Certain mutagens and carcinogens can be activated in a similar way by different (non-orthologous) forms in rat and man, confirming that studies on animals, directed ultimately to man, can be indicative but not predicative of chemical mutagenesis and carcinogenesis. PMID- 7771105 TI - Biotransformation of a new synthetic retinoid, 4-[(5,6,7, 8-tetrahydro-5,5,8,8 tetramethyl-2-naphthyl)carbamoyl] benzoic acid (Am-80), in the rat. Structure elucidation of the metabolites by mass and nmr spectrometry. AB - 1. The major metabolites of Am-80 in rat bile were examined by tlc radiochromatography and hplc-radiochromatography after the intravenous administration of 14C-Am-80, and > 15 metabolites were detected. 2. Intact and Glusulase-treated bile were analysed by both tlc-radiochromatography and hplc radiochromatography. As both samples gave similar patterns in both chromatography systems, we have concluded that neither glucuronide nor sulphate conjugates were present. 3. 2H3-Am-80 and 2H6-Am-80 were administered to rats, and the major metabolites in bile were detected and their structures elucidated by GC-MS. 4. The chemical structures of seven major biliary metabolites, including unchanged Am-80, were identified by mass and two-dimensional nmr spectrometry, and included 6-hydroxy-Am-80 (M-3), 7-hydroxy-Am-80 (M-4), 6-oxo-Am-80 (M-5), unchanged Am-80 (M-0) and the taurine conjugates of M-3 (M-1), M-4 (M-2) and M-0 (M-6). PMID- 7771107 TI - Metabolism of tetramethrin isomers in rat: II. Identification and quantitation of metabolites. AB - 1. To examine the metabolic fate of (1RS, trans)- or (1RS, cis)-tetramethrin [3, 4, 5, 6-tetrahydrophthalimidomethyl (1RS, trans)- or (1RS, cis)-chrysanthemate], rat was administered a single oral dose of trans- or cis-[alcohol 14C]tetramethrin at dose levels of 2 or 250 mg/kg. 2. The radiocarbon was almost completely eliminated from rat within 7 days after administration in all groups. 14C-recoveries (expressed as percentages relative to the dosed 14C) in faeces and urine were 38-58 and 42-58% respectively in rat administrated trans-[alcohol 14C]tetramethrin, and in faeces and urine were 66-91 and 9-31% respectively in rat administered cis-[alcohol-14C]tetramethrin. 3. Fourteen metabolites found in excreta were purified by using several chromatographic techniques and identified by spectroanalyses (nmr and MS). Five sulphonate derivatives and three dicarboxylic acid derivatives were found. 4. The main metabolites were sulphonate derivatives in the faeces, and in the urine, alcohols, dicarboxylic acid and reduced metabolites derived from the 3,4,5,6-tetrahydrophthalimide moiety. PMID- 7771108 TI - Fate of dimethylamine in rat and mouse. AB - 1. [U-14C]-dimethylamine hydrochloride was administered by gavage (20 mumol/kg body weight) to adult male Wistar rat and CD1 strain mouse. 2. In both species, urine was the main route of excretion with the majority of radiolabel (91%) being voided during the first day. Additional small amounts of radioactivity were detected in the 24-72 h urine (2%), in faeces (2%) and amidst exhaled air (1%), with minor amounts remaining within the carcass (1%) after 3 days. 3. Metabolism was limited to demethylation, with the majority of the compound (89% dose; 96% urinary radioactivity) being excreted unchanged. PMID- 7771106 TI - Piperine effects on the expression of P4502E1, P4502B and P4501A in rat. AB - 1. Treatment of rat with piperine (PIP) (1.4 mmol/kg, 3 days ip injections) resulted in an approximate two-fold increase in total liver microsomal P450 content relative to that in uninduced animals. 2. 4-Nitrophenol and aniline hyroxylase activities in the hepatic microsomes prepared from rat treated with PIP decreased by 30 and 28% respectively as compared with control. Immunoblot analyses also revealed decreased P4502E1 levels in hepatic microsomes from PIP treated animals. 3. In contrast with P4502E1 suppression, hepatic 2B1 and 2B2 levels were significantly increased in PIP-induced animals, as evidence by both metabolic activity and immunoblot analysis of the liver microsomal fractions. The rate of hexobarbital hydroxylase activity in microsomes from PIP-treated animals was markedly elevated and was inhibited by approximately 62% in the presence of monoclonal anti-P4502B IgG. Immunoblot analyses demonstrated that P4502B1 and 2B2 levels in hepatic microsomes from PIP-treated animals were comparable with those from phenobarbital-treated animals. 4. 7-Ethoxycoumarin deethylase activity was elevated approximately two-fold in PIP-induced animals and was 17% of that derived from 3-methylcholanthrene-induced animals. 7-ethoxycoumarin deethylase activity in PIP-induced hepatic microsomes was inhibited 63% in the presence of monoclonal anti-P4501A antibody. Immunoblot analysis confirmed the increase in P4501A levels by PIP, which was 15% of that in hepatic microsomes from 3 methylcholanthrene-induced animals. 5. PIP treatment failed to affect microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GST) expression, as indicated by immunoblot analyses using polyclonal antibodies toward mEH and GST subunits Ya, Yb1, Yb2 and Yc. 6. These results demonstrate that PIP treatment suppressed P4502E1 expression and enhanced 2B and 1A expression, whereas this agent failed to affect hepatic mEH and GST expression. PMID- 7771109 TI - Disposition and metabolism of a novel diurea inhibitor of acyl CoA: cholesterol acyltransferase (YM17E) in the rat and dog. AB - 1. We have investigated the disposition and metabolism of YM17E after intravenous and oral administration in the rat and dog. 2. Bioavailability of YM17E was 5-9% at oral doses of 3-30 mg/kg in rat, and 9 and 13% at oral doses of 10 and 30 mg/kg in dog. 3. Five N-demethylated metabolites, which have significant pharmacological activity, were found in rat and dog plasma after oral administration. Plasma concentrations of each of these metabolites were comparable with that of unchanged drug. 4. When 14C-YM17E was administered to rat, AUC of unchanged drug was 7% of that of radioactivity. However, AUC of the combined concentration of unchanged drug and five active metabolites was about 50% of that of radioactivity, indicating that the pharmacological activity of the agent was maintained in spite of its biotransformation. 5. After oral administration of 14C-YM17E at a dose of 10 mg/kg to rat, radioactivity was distributed widely to almost all tissues except the brain. The concentration of radioactivity in the liver, one of the target organs, was 65 times higher than that in plasma at 1 h after administration. 6. A significant amount of radioactivity in the liver was located in the microsomal subfraction, which contains much acyl CoA:cholesterol acyl transferase activity. More than 50% of this microsomal radioactivity was derived from unchanged YM17E and five active metabolites. 7. From excretion data in the bile duct-cannulated rat, the absorption ratio of YM17E from the gastrointestinal tract in this species was estimated to be at least 40%, suggesting that the low bioavailability of the drug is due to extensive first-pass metabolism. 8. Some 95% of the administered radioactivity was excreted in the faeces of rat following iv or po doses of 14C YM17E. PMID- 7771110 TI - Metabolism of illudin S, a toxic substance of Lampteromyces japonicus. IV. Urinary excretion of an illudin S metabolite in rat. AB - 1. The urinary excretion of a metabolite of illudin S after oral administration to rat has been studied. 2. From an ethyl acetate extract of urine, metabolite 1, a cyclopropane ring-cleavage compound, was identified by liquid chromatographic mass spectrometric analysis 3. A hplc method for determination of the metabolite in rat urine was developed with extraction using Sep-Pak C18 cartridge followed by liquid-liquid extraction. 4. The metabolite excreted during 3 days after administration of illudin S to rat amounted to approximately 10-19% of the dose as free form and 3-5% of the dose as glucuronide. PMID- 7771112 TI - Endemic goitre and cretinism in the Simbai and Tep-Tep areas of Madang Province, Papua New Guinea. AB - In the late 1960s and early 1970s a mass campaign of iodized oil injections was carried out in Papua New Guinea as an interim measure to improve iodine status in the population and to prevent endemic goitre and endemic cretinism. Following informal reports of children with neurological abnormalities resembling endemic cretinism in two areas of Madang Province, the Simbai and Tep-Tep Subdistricts, surveys were conducted in these areas in 1985 to establish prevalence rates of goitre and cretinism in order to determine whether they had returned as public health problems. 42% of the Simbai population and 38% of the Tep-Tep population attended for examination. Amongst those surveyed, the visible goitre rate was low: 0.1% in the Simbai and 2.5% in the Tep-Tep area. Although the iodized oil patrols were carried out a decade previously, goitre does not seem to have re emerged in the area to the levels reported previously. In the Simbai villages surveyed, there were nine individuals diagnosed as suffering from cretinism, three of whom were thought to have been born after the last iodized oil patrol in the area. In the Tep-Tep villages, eight subjects were diagnosed as suffering from cretinism, all of whom were thought to have been born before the iodized oil patrols. A number of younger children with neurological abnormalities which did not fulfil criteria for endemic cretinism were also seen in both areas. Because of the difficulties in diagnosing endemic cretinism in young children, it is not possible to conclude that endemic cretinism is no longer a problem in these areas. More work is needed to confirm the results of these studies. This will enable a rational control program to be designed and implemented. PMID- 7771111 TI - Blood pressure, hypertension and other cardiovascular risk factors in six communities in Papua New Guinea, 1985-1986. AB - Surveys of noncommunicable diseases were performed in six communities in Papua New Guinea during 1985-1986. Results are reported here with respect to blood pressure and associated factors in adults. Mean systolic and diastolic blood pressures were lowest, and hypertension was rarest (less than 2%), in three rural/semirural villages on Karkar Island, Madang Province. Intermediate values for blood pressure and moderate prevalence of hypertension (3-6%) were observed in rural and urban Tolai communities in East New Britain Province. A periurban village in the Eastern Highlands Province displayed the highest mean blood pressures and prevalence of hypertension (12% in men and 5% in women). There was a modest rise in mean systolic blood pressure with age in most groups, but the age-related rise in diastolic pressure was much less pronounced. Other cardiovascular risk factors--body mass index (BMI), and plasma cholesterol, glucose and insulin concentrations--were lowest in the least developed rural villages on Karkar Island and highest in the urban Tolai and periurban highland communities. Both systolic and diastolic blood pressures were significantly (and positively) related to age, male sex, BMI and speaking a non-Austronesian language. It is concluded that there is now a considerable variation in the prevalence of hypertension, and the levels of blood pressure and other cardiovascular risk factors, in different communities in Papua New Guinea. PMID- 7771113 TI - Arbovirus disease in Papua New Guinea. AB - It is clear that exposure to arthropod-borne viruses is common in the populations of both Papua New Guinea and Irian Jaya. Clinical disease resulting from these infections has been reported although the paucity of case reports and combined clinical experience suggest that it is rare. Dengue epidemics due to dengue-1 and dengue-2 have occurred and it is likely that dengue-3 is also present in the region. No cases of dengue haemorrhagic fever have been described. Murray Valley encephalitis, Ross River and antigenically related viruses are widespread in Papua New Guinea and Irian Jaya, particularly in the lowland and coastal areas. Antibodies to Japanese encephalitis virus have not been found in blood samples from Papua New Guinea or Irian Jaya. As Papua New Guinea is developed, new areas of the country are opened up and ecosystems are altered. It is important that physicians based in Papua New Guinea, and those who deal with patients living or working here, are aware of the arbovirus diseases which occur and the potential and preventable problems posed by them to both the individual and the community. PMID- 7771114 TI - The role of corticosteroids in the management of infections in Papua New Guinea. PMID- 7771116 TI - Can lymphatic filariasis be eradicated in Papua New Guinea? PMID- 7771115 TI - Blood transfusion services. PMID- 7771117 TI - Diethylcarbamazine in the control of bancroftian filariasis in the Ok Tedi area of Papua New Guinea: phase 2--annual single-dose treatment. AB - The Phase 1 semiannual single-dose 6 mg/kg diethylcarbamazine (DEC) treatment program demonstrated a significant reduction for Wuchereria bancrofti in the Ok Tedi area of Western Province, Papua New Guinea. The rate of detectable microfilaraemia was effectively reduced from 39% to 11% and mean microfilarial (mf) densities from 79mf/20 microliters to 19mf/20 microliters. The Phase 2 annual single-dose treatment of 6mg/kg DEC not only maintained the gains made during Phase 1 but reduced the microfilaraemia rate to less than 5% by 1990, with mf densities remaining stable at less than 20mf/20 microliters, amongst all participating villagers screened within the 5 original villages. The annual treatment program was expanded into 7 remote villages not subject to any form of active vector control. The microfilaraemia rate in these villages declined from 41% before treatment to 17% after only two annual administrations of 6mg/kg DEC, and mf blood densities were reduced from 71mf/20 microliters to 20mf/20 microliters. As was observed in the 5 original villages participating in the program, a significant reduction in splenomegaly associated with the DEC treatment was reported for the 7 villages in the expanded program during Phase 2; enlarged spleen rates were reduced from 50% (1986) to 32% (1990) and from 76% (1988) to 48% (1990), respectively. Malaria rates on the other hand increased slightly or remained stable. Malaria infections associated with W. bancrofti (mixed parasite infections) stimulated a greater splenic response than either parasite detected on its own. PMID- 7771119 TI - Betelnut chewing causes bronchoconstriction in some asthma patients. AB - A previous questionnaire interview had revealed that betelnut chewing may aggravate asthma in 61% of asthma patients attending an outpatient clinic at Port Moresby General Hospital; the rest said it had no effect. The aim of the present study was to verify patients' subjective feelings through objective measurements. 7 asthma patients (Group C) who said betelnut aggravated their asthma, 8 asthma patients (Group B) who denied any effect and 8 nonasthmatic, healthy subjects (Group A) were given betelnut with accompanying ingredients and asked to chew as they would usually chew it. Their spirometric forced expiratory volume in the first second (FEV1) readings, heart rate and blood pressure were monitored before and after this challenge. Group A nonasthmatic subjects experienced only minor rises and falls in their FEV1 in response to betelnut chewing. 3 patients in Group B experienced overall rises (mean maximal % rise 25 +/- 19) while 5 patients had overall falls (mean maximal % fall 11 +/- 6). In Group C 1 patient had an overall rise in her FEV1 (maximal rise 10%) while 6 patients had falls (mean maximal % fall 22 +/- 7). In all groups the heart rate increased in response to betelnut. Betelnut chewing caused bronchoconstriction as demonstrated by decreases in FEV1 in a majority of the asthmatic patients studied; hence betelnut may act as a trigger factor for their asthma. In a few others increases in FEV1 were noted, while the rest experienced only minor changes. PMID- 7771118 TI - Introduction of an integrated community-based bancroftian filariasis control program into the Mt Bosavi region of the Southern Highlands of Papua New Guinea. AB - In mid-1987 a baseline microfilarial prevalence survey was conducted among five villages in the Mt Bosavi region of the Southern Highlands Province of Papua New Guinea. Through use of the Nucleopore filtration technique, it was determined that 48% of villagers had detectable microfilaraemia. The highest prevalence was documented in Fogomaiyu, where the microfilaraemia rate was 92%. On the basis of this initial survey and the expressed interest of the community, the Division of Health in the Southern Highlands Province undertook an integrated community-based pilot control program. The project used two principal control methods: (a) drug treatment with low-dose diethylcarbamazine citrate (DEC) distributed to the community weekly and (b) vector control with permethrin-impregnated bednets. Results six months after the intervention indicate that the program was successful in reducing microfilaraemia at Fogomaiyu village from 92% to 6%. The reduction is principally related to the effects of DEC, although the bednets, by limiting vector-person contact, are expected to reduce the incidence of both filariasis and malaria. PMID- 7771120 TI - [Assessing credibility in suspected sexual abuse of children]. AB - Systematic methods for obtaining and evaluating information from children in an interview situation in cases of alleged sexual abuse are described and objections to assessments of credibility are discussed. It is shown that psychological knowledge exists that can contribute substantially to the investigation of sexual abuse allegations. PMID- 7771121 TI - [Children as witnesses of violence: consequences for determining reliability]. AB - For many years testimony by children was considered to be of little value. The authors of the present article do not share the view that the credibility of children should generally be questioned. Different investigations show that even young children are able to make forensically relevant depositions. The roles of developmental stage, memory and suggestibility of children are discussed in detail. A case report of a child who witnessed the murder of both parents demonstrates the importance of age-related aspects of emotional experience, development of memory and the ability of children to recall memories. Even at the first hearings it is important to establish a nonthreatening atmosphere in which the child can feel safe and protected. An experienced child and adolescent psychiatrist should be consulted early on. PMID- 7771122 TI - [School refusal--a catamnestic study on the diagnostic concept ov "school phobia" and "school anxiety"]. AB - Twenty-six patients diagnosed with school refusal were examined 2.4 years after inpatient treatment. The long-term course of patients with "school phobia" (school refusal unrelated to school) and that of patients with "school anxiety" (school refusal related to school) were compared. In addition, an attempt was made to identify variables predictive of a good outcome. The mean age of the 12 patients with "school phobia" and the 14 patients with "school anxiety" was 12.7 years at the start of inpatient treatment. The assessment of psychiatric disturbances was based on structured interviews for parents and adolescents (MEI and MADEL, 1989) and the dimensional assessment scales of functioning for children and adolescents (MSBF). The variables assessed for predictive value were taken from the patients' records during inpatient treatment and from the hospital documentation system. There was no difference in outcome between the two syndrome groups. There was a tendency to less autonomy in the patients with "school phobia". Girls had a better outcome than boys, as did patients with less absence from school prior to inpatient treatment. Overall there was no difference in the outcome of "school phobia" and "school anxiety". Therefore a new classification should be considered. PMID- 7771124 TI - [Credibility and further psychological problems of young children as witnesses in criminal justice procedures: a case study]. AB - A pair of 3 1/2-year-old twins who had possibly witnessed their mother's murder were examined by a child psychiatrist and a child psychologist as part of a judicial inquiry. The procedure developed specially for this purpose, the actual course of the investigation and the evaluation of the findings with regard to psychological aspects of evidence are discussed. The theoretical part of the study deals with the current state of knowledge and the problems relating to evidence given by young children as witnesses. The main emphasis is on general and specific credibility, identification of people associated with the crime, suggestibility and probabilities related to guessing, perceptual and memory performance, and minimization of emotional sequelae in children who are witnesses to violent crimes. The authors conclude that preschool children can be reliable witnesses in preliminary hearings and court proceedings. PMID- 7771123 TI - [Requests for compensation for immaterial damage: child and adolescent psychiatric legal assessment in conjunction with the revised legislation]. AB - Child and adolescent psychiatry is concerned with many forensic questions. Among these, expert testimony about immaterial injury (pain, suffering) in conjunction with claims for compensation is being requested with increasing frequency. Until recently German law took the position that in cases of severe brain damage compensation (smart money) had to be granted only as a symbolic payment because the loss of cognition and lack of suffering excluded a feeling of satisfaction resulting from compensation. The highest court in Germany has now revised its position by introducing a new category of immaterial injury. This additional category refers to cases of severe brain damage where the "loss of personal quality" in itself creates the basis for a claim for compensation. As a result, related medical examinations and evaluations require as careful a description as possible and the use of scales to assess quality of life. PMID- 7771125 TI - [Child psychiatric assessment and the debate regarding the abuse of abuse]. AB - The current discussion on false allegations in sexual abuse cases has led to a polarization in the views expressed about the credibility of children. Some authors even speak of a "child sexual accuse syndrome" or of a "sexual abuse allegation in divorce" (SAID) syndrome. A phenomenological analysis of the multiple reasons for misinterpretations is presented. Instead of stressing the importance only of false positives in child sexual abuse questions, an attempt is made to describe reasons for false negatives. Based on a retrospective analysis of 50 consecutive child psychiatric experts in connection with court cases, there does not appear to be an increase in false accusations. Rather, only about one third of the cases even involved suspected sexual abuse. Sexual abuse allegations were much more frequent in girls than in boys. Of 20 abuse allegations we judge four to be false allegations. In only one of these cases, that of an adolescent girl who had been abused in childhood, was the false allegation intended. PMID- 7771126 TI - The German-Japanese-relationship in medicine. PMID- 7771127 TI - [Differential diagnosis of lumbar intervertebral disk syndrome from the neurosurgical viewpoint--personal surgical experiences with over 3,000 lumbar operations]. AB - Lumbar syndromes belong to the most frequent complaints in medical practice. In a series of 3110 lumbar spine operations differential diagnoses of neurosurgical relevance are represented. Diagnostic measures and operative indications are discussed. PMID- 7771128 TI - [Lumbar nerve root compression: a cooperative project for quality assurance in neurosurgery]. AB - In 1993 a total of 4152 cases of lumbar nerv root compression have been investigated in 11 neurosurgical departments. Beside patient data diagnostics, treatment and course as well as neurological status before and after treatment were subjects of this quality assurance study. Special emphasis was put on a detailed evaluation of complications. In more than 91% surgical treatment has been performed, in 5% of these cases after an attempt of conservative treatment. Nearly 9% of the patients have not been operated upon. Recurrent disease has been treated surgically in 10.5%. Most common procedure was flavectomy (69%) with discectomy (80%). The all over complication rate was 14%. Typical surgical complications have been rare with 5%. Neurological deterioration after treatment was also rare with less than 2%. The study was able to reflect the present state of treatment in patients with lumbar nerve root compression and the subjects investigated served well as parameters of quality assurance. PMID- 7771129 TI - [Use of GDC coils in treatment of inoperable aneurysms: report of initial experiences]. AB - The authors report on the endovascular occlusion of intracranial aneurysms with GDC coils in 8 patients. In 2 cases, the diagnosis was made because of subarachnoidal hemorrhage. Three patients complained about headache, and one patient had an oculomotor palsy. The findings were incidental in 2 cases. Angiography demonstrated an aneurysm of the internal carotid artery in 4 of the 6 females and in the 2 males (mean age 50 years) and a basilar artery aneurysm in 4 cases. The indication for endovascular treatment was established after carefully weighing the risks against those of a neurosurgical intervention. It was possible to occlude completely the aneurysm by induced electrothrombosis and to preserve the patency of the main vessel in all cases. One female (case 6) developed a hemiparesis due to embolism of a medial branch six hours after treatment. This receded completely after thrombolysis with urokinase. A second patient showed further growth of the internal carotid aneurysm on the control angiogram obtained after six months. Our initial results are encouraging. With increasing experience, endovascular treatment is expected to become the method of choice for the treatment of most inoperable cerebral aneurysms. PMID- 7771130 TI - [3-dimensional computerized tomography in diagnosis and surgical planning of intracranial aneurysms]. AB - Established alternative methods of visualisation of intracranial vessels--MR angiography and angio-CT--give only two dimensional views similar to angiography. It is a subjective matter of the neurosurgeon's imagination to produce three dimensional views on the basis of these methods. Three dimensional processing of dynamic sequence or helical axial computed tomograms give any number you like of stereo-scopic views of the Willisi circulus. Comparing the usefulness of DSA and 3D-CT in 34 aneurysms, the latter often gives supplementary information concerning the direction, neck and adjacent arteries, helpful in planning surgery treatment. It is difficult or sometimes impossible to separate basal aneurysms (a.c.i.) from sinus cavernosus and skull base by this method, but especially in aneurysms located in the area of a.com.a. and c.m.a. the 3D-CT is sufficient for diagnosis and planning surgical treatment without DSA. PMID- 7771131 TI - Three-dimensional videomonitor in neurosurgery--technical note. AB - The operation microscope was equipped with two small camera heads on both sides, with a 35-mm still camera, and with or without a binocular observer tube. These camera heads were connected with 3-dimensional (3D) converter. Authors can observed the 3D images of the operation field on a monitor T.V. through polarization glasses. The microscope with two camera heads is easy to handle because these camera heads are small and light. This is a promising monitor system in microsurgery. PMID- 7771132 TI - [Correlation between the gradient constant of the theoretical pressure volume diagram (PVD) and the pressure volume index (PVI) in relation to brain pulse amplitude-mean pressure function]. AB - In 54 neurosurgical patients--suffering from intracranial tumors, hydrocephalus or different kinds of brain injury--a catheter was implanted in the lateral ventricle for continuously monitoring of the intracranial pressure (ICP). The intraventricular injection of defined amounts of sodium clearance (1-2 cm3) was followed by increased values of intracranial mean pressure--(pm) and pulse amplitude- (PA). The recorded data showed a high significant correlation after regression analysis. After determination of the pressure-volume-index (PVI) and the theoretical pressure-volume-diagram it was examined whether there is a linear correlation between the parameters of the craniospinal space (id) reserves (constant of gradient, (PVI, K of PVD)) and the gradients (CA) of the linear PA PM-function. A significant linear relationship, however of weak degree, could be found between these two parameters. The linear PA-PM-function, therefore, can only be understood in restricted circumstances as a direct parameter of the intracranial spacial reserves. The underlying facts of these problems are dealt within this paper. PMID- 7771134 TI - [Endemic cholera foci in Africa]. PMID- 7771133 TI - Computerized tomography in the assessment of brain shifts in acute subdural hematoma. AB - Computed tomography (CT) was used to characterize brain shifts in 30 adult patients (mean age 51.9 years) with fatal supratentorial acute subdural hematomes (ASH) who were admitted within 3 hours of the head trauma. The Glasgow Coma Scale (GCS) score, hematoma width, and midline shift were tabulated. The width of the cistern surrounding the brainstem (CSBS) and the distance from the floor of the fourth ventricle to the posterior clinoid process (IVv-PC) were measured. Opening (+) or disappearance (-) of the suprasellar cistern (SC) was determined using axial CT. The data were compared with those in agematched controls (n = 26) using the Wilcoxon and Kruskal-Wallis tests. The hematomas in the SC(-) group (n = 22, mean GCS score: 3.8 +/- 1.0) were wider (p = 0.02) than those in the SC(+) group (n = 8, mean GCS score: 4.7 +/- 1.5). The CSBS in the SC(+) group was significantly smaller than that in the controls (p < 0.01). In the SC(-) group the CSBS was smaller and the IVv-PC was significantly larger than those in the controls (IVv-PC; p < 0.01) and the SC(+) group (IVv-PC; p < 0.05). In the evolution of brainstem shifts in ASH, when the SC is open the predominant vector is in the direction of the skull base, while when the SC is not observed, an axial vector shifts the brainstem. PMID- 7771135 TI - [An operative analysis of the cholera epidemic in the Republic of Dagestan using a computer database]. AB - The epidemiological information on cholera epidemic in Daghestan during the period of June 6 to October 21, 1994, based on the data obtained from 2,327 patients and Vibrio carriers in 184 settlements of 27 regions, 8 towns and 1 housing estate, was collected, systematized and analyzed with the use of the data base (DB). The use of DB made it possible to carry out the surveillance of the level of and dynamics of morbidity and infections rates, to determine the territories of risk, the age and social groups of risk, the active routes and factors of transmission. DB may be used for analyzing of operative and current epidemiological information in cholera and other infections. PMID- 7771136 TI - [The mechanisms of the intrafocal and territorial spread of cholera in the Republic of Dagestan]. AB - The description of the epidemic manifestations of cholera in the Republic of Daghestan at the period of the seventh pandemic, linked with the action of such common transmission factors as water, food and everyday contacts, is presented and their role in the territorial spread of this infection is evaluated. The analysis of family foci in the Derbent and Kaiakent regions in 1994 is given; the conclusion is made that a low sanitary level of human dwellings leads to a wide spread of cholera among close relations due to the action of water, alimentary and contact factors of transmission. PMID- 7771137 TI - [Cholera in the Republic of Dagestan]. AB - Cases of cholera were registered in Daghestan in all pandemics with the exception of the fourth one. For the first time the import this infection by pilgrims returning from their hajj by motor transport and traveling through the countries of southwest Asia was registered. 184 settlements of 27 regions, 8 towns and 1 housing estate were involved in the epidemic process, the number of registered cholera cases and Vibrio carriers being 2,327. High contamination rates were detected in regions situated in different geographical zones. Everyday contacts and the alimentary route were the main routes of transmission during this epidemic, while the role of the water route was considerably less important. PMID- 7771138 TI - [The use of a cholera coagulating diagnostic agent under the cholera epidemic conditions in Dagestan]. AB - Dried cholera diagnosticum for the slide coagglutination test was obtained. The diagnosticum, found to be highly active and specific, permitted the detection of Vibrio cholerae in the analyzed material at a concentration of 10(6)-10(8) microbial cells/ml. The diagnosticum was used during cholera epidemic in Daghestan for the detection and rapid identification of cholera vibrios. In all cases the positive results of the coagglutination test were confirmed by other investigation methods (no cases of hyperdiagnosis was registered). The production of these diagnostica in small batches on the basis of specialized research laboratories was recommended. PMID- 7771139 TI - [The epidemiological characteristics of cholera in the Shamil'skii Mountain District of Dagestan]. PMID- 7771140 TI - [Cholera in the plains area of Dagestan]. PMID- 7771141 TI - [The characteristics of cholera prevalence and of the performance of epidemic control measures in small settlements of Dagestan]. AB - The present work deals with summarizing the experience obtained by the specialized antiepidemic brigade of the Rostov-on-Don Research Institute for Plague Control in the work on the liquidation of cholera in some regions of Daghestan with a view to discussing the problems of improvement of anticholera measures. The characteristic features of the epidemic process were its explosive character, sparseness of the foci of infection, the prevalence of its transmission through everyday contacts (family contacts and intensive tribal contacts) and essential delays in taking anticholera measures due to sudden appearance of outbreaks, remoteness of small settlements and the lack of manpower and means for carrying out anticholera measures at a given place and time, as well as delays in epidemiological analysis carried out by local health service bodies. Delays in carrying out such measures led to the spread of infection both within settlements and in the whole region and further in the republic. The epidemic process was complicated by the antibiotic resistance of V.cholerae strains circulating on this territory. All these factors formed specific epidemic situation which introduced amendments into the organization of anticholera measures. PMID- 7771142 TI - [Cholera in a remote region of Dagestan]. AB - The epidemic situation in a remote region of Daghestan at the period of the cholera outbreak in the republic is considered with the use of concrete examples. The analysis of cases of cholera, as well as Vibrio carriership, at the period of August 5 to October 5, 1994, is presented. The territorial and temporal separation of different cases of the disease and Vibrio carriership were indicative of the periodic import of the causative agent to the territory of the town and the region from other places, unfavorable with respect to cholera, without the involvement of the water factor of infection transmission. Timely and complete antiepidemic measures prevented this infection from acquiring the character of developed epidemic. PMID- 7771143 TI - [The characteristics of the cholera epidemic situation in a separate region of Dagestan]. PMID- 7771144 TI - [Cholera in Makhachkala during the 1994 epidemic]. AB - During the period of epidemic in the Daghestan 51 patients and 27 Vibrio carriers were detected in Makhachkala. A considerable proportion (30.7%) of cholera cases caused by infection imported from regions, unfavorable with respect to cholera, in the presence of pronounced migration of the population was registered. The role of different transmission routes in cases of cholera was as follows: day contacts were responsible for 43.3%, the alimentary route for 28.4% and the water route for 14.9% of cases. The epidemic situation was characterized by a mild and prolonged type of the epidemic process. Mass diseases were prevented by a complex of cholera control measures, among them the emphasis was made on various limitations and prophylactic measures aimed at the rupture of the transmission routes of V. cholerae. PMID- 7771146 TI - [The cholera outbreak in one of the central regions of Dagestan]. AB - The data on the epidemiological analysis of cholera cases in the epicenter of this infection in the Daghestan, viz. in the village of Gerga, Kaiakent District, are presented. The outbreak of cholera was due to the import of this infection by pilgrims from their hajj to Saudi Arabia. The causative agent of the outbreak was the epidemic variant of V. cholerae eltor Ogawa. Everyday contacts were the main route of the transmission and spread of this infection, the water factor playing an insignificant role. Two epidemic waves of cholera were registered in Gerga, each of them provoked the penetration of the infection to other regions of the Republic of Daghestan. PMID- 7771145 TI - [The routes of the spread of cholera in the Shamil'skii Mountain District of Dagestan]. AB - The routes of the spread of cholera were analyzed in 273 patients and Vibrio carriers during the outbreak of cholera in a mountainous region of Daghestan during the period of July 18 to September 4, 1994. Cholera was found to spread mainly after funeral repasts and condolence visits accompanied by the dispensation of foodstuffs, transmission being realized through alimentary and contact routes. Under the conditions of the absence of the centralized water supply system in mountain villages and the contamination of water in open reservoirs it was found to be expedient to use, in addition to the recommended complex of antiepidemic measures, small automatic filtration units. PMID- 7771147 TI - [The epidemiology of cholera in Derbent District, Dagestan. The routes of the importation and spread of cholera]. AB - The epidemic of cholera in the Derbent District of the Daghestan was imported into the region. 172 cholera patients and 204 Vibrio carriers were registered in 23 settlements of the region during the period of June 26 to October 12, 1994. The wide spread of this infection was facilitated by high migration activity of the population and the belated introduction of measures for limiting migration. The most severe outbreaks of cholera were observed in Derbent and in the villages of Mamedkala and Morskoe. PMID- 7771148 TI - [The epidemiology of cholera in Derbent District. The characteristics of the epidemic process]. AB - Cases of cholera in the Derbent District of the Daghestan took predominantly mild and moderate clinical forms. The ratio of patients to Vibrio carriers was 1:1.25. The etiological agent of the epidemic was V. eltor, serovar Ogawa. Cholera patients were of greater epidemiological importance as the sources of infection in comparison with Vibrio carriers. Carrier state after convalescence was observed in 1.1% of cases. The population was infected with cholera, as a rule, through everyday contacts and in more rare cases by the water route. The highest rate of contamination with V. cholerae was registered in the age group of 0-2 years. PMID- 7771149 TI - [The cholera epidemic in mountainous regions of Dagestan in relation to the probable role of the water factor in its spread]. AB - The follow-up of dynamics of cholera epidemic in 1994 was made in 4 mountain regions of Daghestan with shared river system. There were 537 infection cases in these regions, which was equal to 1/4 from the total number of cholera patients in Daghestan. The probability of cholera distribution by water way has been shown, which can be related to massive dissemination with V. cholerae in river, drink and waste water both from active, and from local (intrahospital) epidemic sources. Vibrio's exit from cholera hospital became possible after dissemination intrahospital V. cholerae of waste water, after contamination of river water and after formation of secondary sources and cholera waves, which resulted in the prolongation up to 40 days of this infection in mountain regions of Daghestan. PMID- 7771150 TI - [The prevalence of El Tor cholera in 2 regions of Dagestan remote from each other]. PMID- 7771151 TI - [The characteristics of the antibacterial therapy for cholera in Dagestan]. AB - Wide circulation of antibiotic-resistant Vibrio cholerae strains again gives prominence to the problem of etiotropic therapy. The results of the treatment of 428 persons infected with V.cholerae (237 cholera patients and 191 Vibrio carriers) in different regions of Daghestan during the outbreak of epidemic in 1994 are presented. The main criterion of the effectiveness of antibacterial therapy was the determination of the percentage of bacterial relapses. The sensitivity of 118 V.cholerae strains to different antibacterial preparations was studied by the method of serial dilutions. After the clinical use of chloramphenicol 29.7% of bacterial relapses were registered, the in vitro resistance of V. cholerae being 32-64 mkg/ml. After the use of tetracycline 16.5% bacterial relapses were registered with in vitro resistance being the same. The use of the combination of these preparations gave 15% of bacterial relapses. Furazolidone gave 4.3% of bacteria relapses, while after the use of ciprofloxacin 2.8% of bacterial relapses were registered with in vitro sensitivity equal to 0.25-0.5 mkg/ml. Ciprofloxacin was recommended for the treatment of cholera patients and furazolidone, for the treatment of Vibrio carriers. PMID- 7771153 TI - [The bacteriophage lysis-susceptibility properties of Vibrio cholerae strains isolated in separate regions of Dagestan in 1994]. AB - The study of the properties of V. cholerae strains isolated in June-September 1994 in the Daghestan revealed that they belonged, according to their specific properties, to typical representatives of V. eltor, serovar Ogawa, but a great part of them (67.2%) was not lysed by diagnostic cholera bacteriophages. Experiments with different batches of diagnostic cholera bacteriophages showed the necessity of their further improvement. PMID- 7771152 TI - [The characteristics of Vibrio cholerae isolated in Dagestan in 1994]. AB - A high degree of resistance to cholera diagnostic phages and carriership of prophages characteristic of V. cholerae eltor strains vct+ were shown to be the specific features V. cholerae isolated in Daghestan during the period of June October 1994. Among the strains under study, isolated respectively in 12 and 18 out of 19 regions of Daghestan, a high proportion was found to have resistance to tetracycline (65%) and chloramphenicol (28.6%). Moreover, some strains were found to be resistant to furagin and erythromycin. Out of 242 strains resistant to antibacterial preparations, 163 strains were found to have multiple resistance. Gentamicin, cipropfloxacin and doxicycline were shown to have high in vitro activity with respect to the strains under study. PMID- 7771154 TI - [The preservation of the causative agent of cholera in the water supplies of the central regions of Dagestan (experimental data)]. AB - The acidic pH of water of surface water reservoirs in Izberbash and two adjoining regions, including sea water, seems to be unfavorable for the prolonged preservation of Vibrio cholerae eltor, but additional ecological investigations are necessary to study the possibility for infection to take root at this territory. Water from the Zam-Zam spring, if contaminated with V. cholerae, may serve as a transmission factor, but the duration of its action is limited by the survival term of V. cholerae. The water route of transmission did not play any essential role in the spread of cholera in the central regions of Daghestan. PMID- 7771156 TI - [The outer membranes of Vibrio cholerae as a potential component in a chemical vaccine]. AB - The results of the study of the preparation of V. cholerae eltor membrane, obtained by the lysis and inactivation of microbial cells with urea and the subsequent differential centrifugation and nuclease treatment. As revealed in this study, the outer membrane preparation, when introduced parenterally and orally to mice, induced pronounced immunity to experimental cholera infection and the production of vibriocidal antibodies in high titers. The treatment of V. cholerae eltor membranes with trypsin led to further increase of the immunogenic potency of the preparation. The protective action of V. cholerae eltor outer membranes considerably exceeded the protective effect of currently used whole cell eltor vaccine. This opens prospects for using the above-mentioned preparation for the improvement of chemical vaccine as a component ensuring the formation of antibacterial immunity. PMID- 7771155 TI - [The properties of the Vibrio cholerae strains isolated in large districts in western Dagestan in 1994]. AB - 190 V. cholerae cultures isolated by the specialized antiepidemic brigade of the Rostov-on-Don Research Institute for Plague Control in the Khasavyurt, Babayurt and Novolaksk regions of Daghestan in August-October 1994. All isolated strains were typical with respect to their morphological and cultural properties and could be agglutinated (with the exception of one strain) to the titer or half titer with diagnostic cholera serum and Ogawa serum. 4 strains had signs of RO dissociation, 4 strains were agglutinated with Inaba serum in a low titer. All strains were resistant to diagnostic bacteriophages. Cyproxin and doxicycline proved to be the most active agents for the treatment of patients. Agglutinins, vibriocidins and antidermonectrotic antibodies in diagnostic titers were detected in the sera of all patients and Vibrio carriers. PMID- 7771157 TI - [The epidemiological characteristics of cholera in the Republic of Dagestan. An assessment of the epidemic-control measures]. AB - Retrospective analysis of epidemic cholera manifestations was made in Daghestan using the data of operative epidemic analysis of the break in 1994. Unexpected prolongation of epidemic process of cholera for Daghestan, which was imported by pilgrims from Southern-Western Asia, has been shown using climate-geographical social-demographical and sanitary-hygienic peculiarities. Common laws of development of epidemic complications were demonstrated, as well as the main ways of infection transmission of great number of Daghestan settlements in epidemic process. The importance of antiepidemic means and significant role of created specialized antiepidemic groups have been emphasized in rapid carrying out of means in infection focus, including massive investigation of people in settlements. PMID- 7771158 TI - [The isolation of the Vibrio cholerae dermotoxin and the characterization of its biological properties]. AB - The dermonecrotic factor (dermotoxin) inducing skin necrosis in rabbits has been isolated from V. cholerae strain B-53-2-38 and partially purified. Dermotoxin has a molecular weight of about 110 kD and possesses pronounced cytotoxic and general toxic action, differing from that of enterotoxin. The introduction of this factor into the blood and peritoneum of laboratory animals causes their death. PMID- 7771159 TI - [The destructive activity of vibrios]. PMID- 7771161 TI - [New species of pathogenic vibrios isolated from people and the water of the Black and Baltic seas]. PMID- 7771160 TI - [The discovery of a dermonecrotic factor in Vibrio cholerae non O1 and other pathogenic vibrios]. PMID- 7771162 TI - [Cases of intrahospital cholera infection]. PMID- 7771164 TI - Torsades de pointes and aborted sudden death after implantation of a cardioverter defibrillator. AB - Recent publications have demonstrated that the implantable cardioverter defibrillator (ICD) improves survival in patients with ventricular tachycardia (VT) or fibrillation (VF) by reducing arrhythmic death. We report the case of a patient with a history of an old myocardial infarction and a left ventricular dysfunction, who presented four episodes of syncope associated with a hemodynamically not well tolerated sustained VT, who had easy inductible clinical VT during electrophysiologic study and required an ICD. After a follow-up of 2 months, the patient presents a complete AV block and multiple episodes of torsades de pointes that sometimes degenerate into VF. The ICD delivered 64 adequate and well-tolerated shocks during 10 hours before and during the hospital admission. We programmed a VVI pacing rate at 65 bpm and no more arrhythmia was observed. The left ventricular ejection fraction was not altered afterwards. In conclusion, we experienced the temporary efficacy of the ICD in the treatment of incessant torsades de pointes, without myocardial injury. PMID- 7771163 TI - [A case of the importation onto the territory of Russia of cholera caused by a new serovar]. AB - Materials on the import of rarely occurring Vibrio cholerae, not belonging to group O1 of serovar O139, to the territory of Russia are presented. The clinical picture of a cholera case is described and the biological properties of V. cholerae, serovar O139, are presented. A suggestion has been made concerning the appearance of a new V. cholerae serovar, capable of ousting V. cholerae eltor, the cause of the seventh pandemic. PMID- 7771165 TI - Percutaneous balloon pericardiotomy for management of cardiac tamponade in a patient with lung cancer and large pericardial effusion. AB - We describe the case of a 32-year-old man with lung cancer involving the pericardium on which we performed pericardiotomy, using a balloon dilating catheter, to create a non-surgical pericardial window. For the percutaneous creation of pericardial window we advanced into the pericardium by subxiphoid approach a 0.035 inch guide wire through a 7f. pig-tail catheter. Subsequently a 22 mm diameter, 4 cm long balloon dilating catheter was advanced to the parietal pericardium and inflated for about 60 seconds until a tear in the pericardium was formed. We believe that percutaneous balloon pericardiotomy is helpful in the management of large pericardial effusions particularly in patients with malignancies and poor condition. PMID- 7771166 TI - In memoriam. Professor Rene Pannier (1913-1994). PMID- 7771167 TI - Platypnea-orthodeoxia syndrome. PMID- 7771168 TI - The response of the ageing heart to regular physical exercise. An echo and Doppler study. AB - In upper middle age healthy subjects the functional cardiac reserve is known to be decreased (Port et al., 1980; Aubert et al., 1994). On the other hand regular physical exercise improves the cardiovascular function (Nishimura et al., 1980). The aim of this study was to establish whether regular physical exercise is associated with a significant change in the ageing process of the cardiovascular system. PMID- 7771169 TI - An estimation of the left ventricular diastolic function from the spectral analysis of the fourth heart sound. A Doppler validated study in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is a typical primary cardiac disease characterized by diastolic abnormal function due to both prolonged relaxation and decreased compliance (Sanderson et al., 1977; Spirito & Maron, 1990). Since the contribution of the atrial systole to ventricular filling is usually increased, the appearance of a fourth heart sound (S4) is a common finding in HCM. This sound is related to the ventricular compliance and to the atrial contractility. It is generated during the rapid setting into vibration of the left ventricular walls that results from the rapid rush of the blood due to the atrial contraction (Nishimura et al., 1989; Tavel, 1978). The aim of this study is to look for relationships between the frequency peak of S4 and various mono- and two dimensional echocardiographic parameters in order to identify those cardiac structures involved in its genesis and obtaining an estimation of the stiffness of the acoustic vibrating system with a simply vibratory model (Baracca et al., 1991). PMID- 7771170 TI - Genesis and acoustic quality of the physiological fourth heart sound. AB - The genesis of the fourth heart sound (S4) is commonly related to the rapid set in vibration of the left ventricular walls, resulting from the rapid inflow of the blood due to the atrial contraction (Nishimura et al., 1989). S4 can be recorded in normal young subjects as an expression of physiologic atrial dynamics but it is more common in pathologic conditions characterized by decreased ventricular distensibility (Tavel, 1978). Employing the spectral analysis of heart sounds (Longhini et al., 1979; Longhini et al., 1981; Aubert et al., 1984) we searched for the relationship between different components of the frequency spectrum of S4 and various echocardiographic parameters, with the aim of identifying the cardiac structures involved in its genesis (Longhini et al., 1989; Baracca et al., 1991). PMID- 7771171 TI - Phonomechanocardiographic parameters in patients with atrial septal defect. AB - The purpose of the present study was to noninvasively evaluate left (LV) systolic and diastolic function in patients with atrial septal defect (ASD) using the phonomechanocardiogram. We studied 40 patients with atrial septal defect, 16 males and 24 females, ages ranging from 6 to 56 years (mean 21.1 years), consecutively observed before surgery in our institution, during a four year period. We measured the systolic time intervals (Q-A2c, Q-S1, ICT, PEP, LVETc, PEP/LVET), the Apex Cardiographic (ACG) diastolic parameters A2-Oc and A/H and the hemodynamic variables Qp/Qs, Pulmonary Vascular Resistance (PVR) and Left Ventricular End Diastolic Pressure (LVEDP). We compared the data with 74 normal individuals using the Student t-test and linear regression analysis. We found significant Q-S1 lengthening (81.2 +/- 16.4 ms, p < 0.001); PEP, ICT and A2-Oc were significantly reduced (101.2 +/- 21.7 ms, p < 0.001, 20.0 +/- 5.3 ms, p < 0.05 and 117.1 +/- 26.3 ms, p < 0.001, respectively) and A/H was significantly increased (17.4 +/- 12.1%, p < 0.005). Except for the case of Q-S1, where there was a weak positive linear correlation with Qp/Qs (r = 0.37), we found no correlation between the other parameters and Qp/Qs or PVR. Sixty-seven percent of the patients had Q-S1 prolongation and a Q-S1 > 76.2 ms identified left-right shunts > 2 with a positive predictive value of 82%; 62% of the patients had a reduced A2-Oc and a A2-Oc < 110 ms identified shunts > 2 with a positive predictive value of 90%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771172 TI - Diltiazem effects on left ventricular function preliminary results of 12 patients evaluated by calibrated apexcardiogram. AB - Diltiazem is a calcium channel blocker whose effects on left ventricular function (LVF) are controversial. We studied 12 patients with ischemic heart disease (IHD) before starting and 15 and 30 days after having initiated Diltiazem 60 mg t.i.d. LVF was accessed by means of the normalized indexes of the calibrated apexcardiogram: nS for systolic LVF evaluation and nA for diastolic LVF evaluation. Recent works have shown that these indexes have a good correlation with invasive parameters of LVF. We verified that nS did not change and nA decreased significantly (p < 0.05) after Diltiazem. We preliminary concluded that Diltiazem has no deleterious effect on LV systolic function and improves LV diastolic function, by decreasing nA, a parameter which correlates well with LV end diastolic pressure. PMID- 7771173 TI - Doppler echocardiographic evaluation of left ventricular relaxation in patients with coronary artery disease. AB - The time constant of the left ventricular isovolumic pressure decline (Tc) was determined according to the Weiss equation in 23 patients with chest pain who underwent cardiac catheterization. Out of them 15 patients had significant coronary artery stenosis (CAD). Tc was compared to 21 diastolic Doppler data derived from the transmitral inflow. We could predict the Tc from Doppler data using a stepwise multiple regression model, Tc = (0.072 x A-Vpeak)-(0.387 x A dect)-(0.137 x E-dect) + 0.050 (r = 0.7493, p < 0.0011 SEE = 0.007 All Doppler data and the predicted Tc were examined among the CAD and the healthy groups, the predicted Tc and E/A ratio indicated the best discriminant functions. PMID- 7771174 TI - Prognostic value of simple exercise test parameters in patients with dilated cardiomyopathy. AB - The prognostic value of maximal exercise capacity as well as that of the simple exercise systolic blood pressure and heart rate variables were evaluated in 50 patients with dilated cardiomyopathy. Patients were treated beside digitalis and/or diuretics with vasodilators aggressively. Exercise was performed on an upright bicycle ergometer. Continuous, multistage, symptom limited, maximal tests were carried out. Patients were followed up for 23.5 +/- 15.2 months. Both one way and multivariate analyses of data showed, that not only the maximal exercise capacity related significantly to the survival, but the several simple systolic blood pressure and heart rate variables (their values at peak exercise and their increase during the test) did so as well. Considering parameters separately, maximal exercise capacity was found the strongest predictor of survival, though the power of the calculated rate-pressure product at peak exercise, that of the systolic blood pressure at peak exercise as well as that of the increase in heart rate during the test proved nearly as strong as the maximal exercise capacity did. Anyway, the multivariate analysis showed that the former parameters were dependent on maximal exercise capacity. Some parameters with individual prognostic value proved independent from each other. Combined consideration of the systolic blood pressure at peak exercise and the increase of heart rate during exercise resulted in the highest predictive power which exceeded even the power of maximal exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771175 TI - Cibenzoline in the prevention of recurrence of supraventricular arrhythmias. AB - Hundred and twenty-three outpatients were treated with oral cibenzoline for 3 months in order to test the efficacy and safety of the compound in the prevention of the recurrence of supraventricular arrhythmias. The dose was 260-390 mg/day for those under 70 and 130-260 mg/day for those over 70 years. All patients were converted to sinus rhythm before entry to the study and 95 patients had previously been treated with one or more drugs which had been discontinued due to lack of effect and/or poor tolerability. In 21 patients (17%) recurrence was documented by ECG or Holter monitoring, cibenzoline thus being effective in 83%. In 35 other patients there was a return of symptoms but no confirmation of recurrence. There were no relevant changes in blood pressure or heart rate. PR, QT and QTc intervals were stable but mean QRS interval increased slightly during the first week before stabilizing. Cibenzoline was discontinued because of adverse events in only 10 patients (8.1%). The most frequent complaints were nausea, vertigo and faintness. Seventy-two per cent of patients rated their well being as "well/very well" at month one compared with 84% at month three. Cibenzoline is an appropriate first line choice in this indication. PMID- 7771176 TI - Percutaneous balloon pericardiotomy as a therapeutic alternative for cardiac tamponade and recurrent pericardial effusion. AB - A terminally ill patient with cardiac tamponade secondary to metastatic breast cancer was successfully treated by percutaneous balloon pericardiotomy. The procedure was performed through subxiphoid approach under local anaesthesia and its beneficial effect was maintained until the patient's death from her primary disease. A second, 86-year-old, debilitated patient and a third 52-year-old patient were managed likewise and both left hospital relieved from recurrent severe pericardial effusions. The later two patients have shown no signs of recurrence for fifteen and twelve months respectively. PMID- 7771177 TI - "Accurate" noninvasive detection of diastolic dysfunction by current techniques: fact or fancy? AB - To evaluate clinically left ventricular (LV) diastolic performance has been recognized in recent years to be an important part in cardiac evaluation, since diastolic abnormalities occur early and are sensitive indicators of diseased myocardium as well as determinants of cardiac output. Data on LV diastolic function are noninvasively acquired in recent years in most laboratories from: 1) radionuclide angiography, 2) echocardiography (M-mode and 2D) and 3) Doppler echocardiography. All these widely accepted and used methods for the detection and quantification of diastolic dysfunction are based on the assessment of indices of either rate of ventricular filling or rate of change of LV diameter and wall thickness during diastole. PMID- 7771179 TI - XIIIth Annual scientific sessions of the Belgian Working Group on Cardiac Pacing and Electrophysiology. October 1, 1994. Abstracts. PMID- 7771178 TI - Systolic segmental disappearance of internal mammary artery graft. Correlation with prolonged spasm of the graft. AB - Vasospasm of the saphenous vein and internal mammary grafts may develop spontaneously under several conditions. We present for the first time spasm of a left internal mammary artery bypass graft during coronary arteriography. A patient who underwent coronary artery bypass operation 4 years ago was recatheterized because he developed chest pain. Selective catheterization of the left internal mammary artery graft showed disappearance of its lumen at its distal part during systole, whereas the patient developed angina. These phenomena disappeared after intravenous nitroglycerin administration. PMID- 7771180 TI - GLUT-1 glucose transporter is localized heterogeneously within the microvessels of the mouse hippocampus. AB - We investigated the distribution of the glucose transporter protein within the microvessels in the mouse hippocampus by immunohistochemical methods with an anti rat brain glucose transporter 1 (GLUT-1) and confocal laser scanning microscopy. All intraparenchymal microvessels in the hippocampus showed intensive immunoreactivity and a heterogeneous distribution of GLUT-1 was seen in the microvessels. These data may suggest that glucose could be heterogeneously incorporated into the endothelial cells of the cerebral microvessels, and therefore morphological and physiological differences may be present among the endothelial cells. PMID- 7771181 TI - Peptidergic innervation of the human prostate, seminal vesicle and vas deferens. AB - Neuropeptidergic innervation of the human prostate, seminal vesicle and vas deferens was investigated by immunohistochemical methods. The innervation pattern of all organs was very dense. Neuropeptide Y- and tyrosine hydroxylase-positive nerve fibers were most abundant and localized mainly in the smooth muscle layer. On the contrary, vasoactive intestinal polypeptide-positive nerve fibers were mainly found beneath the epithelium. Also leu-enkephaline-, peptide histidine isoleusine- and calcitonin gene-related peptide-positive nerve fibers could be observed in all organs, but somatostatin-positive nerves only in the prostate and seminal vesicle and met-enkephalin- and substance P-positive nerves only in the prostate. PMID- 7771182 TI - Hydrogen peroxide (H2O2) production by monoamine oxidase in rat tissues using endogenous catecholamines as substrates. A comparison of catalytic monoamine oxidase histochemistry and recently published catechol-O-methyltransferase immunohistochemistry. AB - Histochemical studies on hydrogen peroxide (H2O2) production by monoamine oxidase (MAOX) using xenobiotic (foreign) catecholamines such as tryptamine or tyramine as substrates may not reveal the true H2O2-production capacity of this enzyme and the potential co-localization and cooperation of MAOX with catechol-O methyltransferase (COMT), the other catecholamine-degrading enzyme. Therefore, in the present study the catecholamine hormones adrenaline (epinephrine) and noradrenaline (norepinephrine) and the catecholamine neurotransmitter noradrenaline as well as the COMT metabolites metanephrine and normetanephrine, which are likely to be the more important MAOX substrates, were used for MAOX visualization in many rat tissues with a cerium-diaminobenzidine-H2O2-Co method. Adrenaline and noradrenaline were autooxidized by Ce3+ and could not be employed; with metanephrine or normetanephrine as substrates MAOX produced considerable amounts of H2O2 in many cells and tissues. Comparisons with immunohistochemical COMT-data for rats from the literature show that MAOX and COMT are co-localized or not. Therefore, different from our current knowledge in rats COMT and MAOX either co-operate in catecholamine degradation or they degrade the respective catecholamines alone. PMID- 7771183 TI - New monoclonal antibodies recognizing phosphorylated proteins in mitotic cells. AB - Three monoclonal antibodies which showed strong staining of mitotic cells by screening on the human cell line MCF-7 were isolated. The antigens detected by the DH7 and BF6 monoclonal antibodies were located predominantly in multiple extranucleolar patches in interphase cell nuclei. In mitotic cells a strong increase in the fluorescence intensity was accompanied by its redistribution into a fine speckled form. Metaphase chromosomes were unstained. Centrosomes, spindle poles or midbodies were not stained either before or after extraction of the cells with Triton X-100 under conditions which preserve microtubular structures. In immunoblots of interphase cell extracts only very few bands reacted with DH7 whereas in mitotic cell extracts approximately 30 bands were stained. BF6 also showed an increase in the intensity and number of bands detected in mitotic compared to interphase cell extracts, and the pattern was clearly different from that obtained with DH7. The BF6 antigen were extracted by 0.5% Triton X-100, whereas the DH7 antigen was not. Dephosphorylation of the antigens strongly reduced the binding of both antibodies as measured by immunoblotting and ELISA assays. The results suggested that BF6 and DH7 detect two different phosphorylated epitopes, each of which is shared by a different subset of proteins from mitotic cells. The third antibody, BD 12, bound to several polypeptides, including one of high molecular weight that appeared to correspond to the NuMA antigen. The epitope recognized by BD 12 was not sensitive to phosphatases. PMID- 7771184 TI - Peptidergic innervation of the bovine vagina and uterus. AB - The distribution of neuropeptide Y, substance P, vasoactive intestinal polypeptide, Leu5-enkephalin, bombesin/gastrin-releasing peptide, calcitonin gene related peptide, somatostatin, cholecystokinin and catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase was studied immunohistochemically in nerve fibres supplying the bovine vagina and uterus. The nerves containing tyrosine hydroxylase or dopamine-beta-hydroxylase and neuropeptide Y-immunoreactivity were particularly numerous in both organs. Substance P, vasoactive intestinal polypeptide and Leu5-enkephalin-containing nerves were less numerous whereas somatostatin and calcitonin gene-related peptide-immunoreactive nerves occurred occasionally. Bombesin/gastrin-releasing peptide and cholecystokinin immunoreactivities were not present in nervous fibers of the bovine uterus and vagina. Generally, the immunoreactive nerve terminals, fibers, networks or nerve bundles were present below the serous membrane, between smooth muscle cells of muscular layers, around blood vessels, in the submucosal layer and below the luminal epithelium of the uterus and cervix. PMID- 7771186 TI - Flow cytometric measurements of intracellular Ca2+ mobilization in isolated rat pancreatic acinar cells after hormone stimulation and action of lectins. AB - Isolated rat pancreatic acinar cells were loaded with the Ca(2+)-sensitive fluorescence dye Fluo 3 in vitro and the intracellular Ca2+ changes were analysed by flow cytometry. Morphology, viability, and loading with the dye were studied by light microscopy. Stimulation with cholecystokinin/pancreozymin (CCK) and its agonist caerulein as well as with carbamylcholine (Jestryl) led to an increase of intracellular calcium ions and a fluorescence peak. The slope and height of the Ca2+ signals were found to be influenced by preincubation of cells with some plant lectins (WGA, UEA, PHA, Con A, LCA, PNA). These effects are discussed with respect to the interaction of lectins with the carbohydrate chains of cell membrane receptors. PMID- 7771185 TI - Changes of enzyme activities in the rat myocardium caused by experimental hypoxia with and without ginkgo biloba extract EGb 761 pretreatment. A cytophotometrical study. AB - Using cytophotometry activity changes of succinate dehydrogenase, glycerol-3 phosphate dehydrogenase and myofibrillar adenosine triphosphatase, were measured in the rat myocardium under normal and different experimental conditions. After hypoxia all enzyme activities were significantly decreased in comparison to the normal situation, and the alterations differed in both ventricles. Ginkgo biloba extract treatment over three months before exposition to hypoxia resulted in a lower inhibition of succinate dehydrogenase, a higher inhibition of glycerol-3 phosphate dehydrogenase and an unchanged activity of adenosine triphosphatase after hypoxia of 20 min. These results were interpreted as a protective effect of the Ginkgo biloba extract on the hypoxic myocardium. PMID- 7771188 TI - A flow cytometric analysis of the DNA content of Paget cells in the epidermis and the tumor of extramammary Paget's disease. AB - In the present study, we have examined whether or not the Paget cells in cases with dermal invasion or metastasis exhibit a different DNA distribution pattern to that seen in the epidermis in extramammary Paget's disease. The DNA contents of Paget cells from the epidermis and the tumor were determined by flow cytometry in two cases of extramammary Paget's disease with tumor formation, dermal invasion and metastases. The DNA histogram of Paget cells from the epidermis of two cases appeared to be close to the normal ploidy, whereas the histogram from the tumors was aneuploid in both cases. Our data suggest that the behavior of Paget cells in the epidermis is different from that in the tumor. PMID- 7771187 TI - A rapid lectin receptor binding assay: comparative evaluation of sea urchin embryo cell surface lectin receptors. AB - Lectin receptor binding assays, such as those that utilize fluorescence, radioactivity or electron microscopy are not designed for rapidly screening hundreds of cell types for the presence or absence of specific lectin receptors. An assay is described here that is designated for this purpose. It utilizes lectins derivatized to agarose beads and can be used to screen many cell types in min. This assay was used to examine lectin receptors on the surfaces of 1-8 cell stage Strongylocentrotus purpuratus sea urchin embryos. The same cells were also assayed using standard fluorescence and agglutinability procedures to ascertain the type of information obtained by the new assay and how it correlates with results from the standard methods. The bead results correlated well with results using fluorescent lectin. Only wheat germ agglutinin bound very strongly in both bead and fluorescence assays, while concanavalin A, Dolichos biflorus, Lens culinaris and Tetragonolobus purpureas did not bind or bound weakly using both methods. Results using a third method, lectin mediated cell agglutination, did not correlate with the bead or fluorescence assays. Lectin receptors were also examined on embryos prepared by two different methods of preventing formation of fertilization membranes, so that coat-free cell surfaces could be studied, the standard dithiothreitol method and a new method using alpha-amylase. Lectin receptors on the cell surfaces of embryos prepared by both methods were nearly identical. The possible functions of WGA receptors, the most prevalent lectin receptors of those studied, that were uniformly present throughout early development of this sea urchin species, are considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771189 TI - Detection of 54-kDa protein overexpressed by chloroquine-resistant Plasmodium berghei ANKA strain in pyronaridine-resistant P berghei ANKA strain. AB - AIM: A 54-kDa protein overexpressed by chloroquine-resistant (CR) Plasmodium berghei ANKA strain was first reported by us. This study is conducted to detect the protein in pyronaridine-resistant (PR) P berghei ANKA strain. METHODS: Immunoblotting analysis and immunoelectron microscopy were used. RESULTS: PR parasites, like CR parasites, mainly overexpressed 2 major bands of 37 (36-38) kDa and 16 (15-17) kDa which were considered to be 2 subunits of 54 (52-62) kDa protein. Three of 7 times of experiments showed a 54-kDa and a 96 (95-100) kDa bands. The proteins were localized to be mainly scattered in cytoplasm of trophozoites, schizonts, and merozoites of erythrocytic stage of P berghei. Some of them were distributed in cytoplasm of erythrocytes infected with parasites. CONCLUSION: Both PR and CR parasites overexpressed the same proteins. PMID- 7771190 TI - Effects of isovanihuperzine A on cholinesterase and scopolamine-induced memory impairment. AB - AIM: To study the effects of isovanihuperzine A (IVHA) on cholinesterase and scopolamine-induced memory deficit. METHODS: AChE and BuChE activities were determined by the colorimetric method of Ellman. The Ki value was determined by the plotting method of Lineweaver and Burk. In a behavioral test, rats were trained to perform a radial arm maze task using a partially baited procedure. RESULTS: The anti-AChE activity of IVHA was comparable to huperzine A (Hup-A), and was more potent than those of physostigmine and galanthamine with an IC50 value of 0.11 mumol.L-1. IVHA was a mixed competitive type with a Ki value of 32 nmol.L-1. It bound to AChE in a reversible manner. IVHA at a dose of 0.2 mg.kg-1 ip significantly reversed scopolamine-induced working memory and reference memory impairments in radial arm maze. CONCLUSION: IVHA is a new potential reversible AChE inhibitor and merits further study as a cognitive enhancer. PMID- 7771191 TI - QSAR of 3-methylfentanyl derivatives studied with neural networks method. AB - AIM: To use neural networks, which simulate the functions of living nervous systems, in QSAR studies; METHODS: Using the back-propagation neural networks program devised by us, combining with partial least squares (PLS) method, we studied the relationships of quantum chemical indices and analgesic activities of 25 3-methylfentanyl derivatives; RESULTS: Through learning process, a good QSAR model was established, and the activities of these compounds were predicted; the correlation between the activities and quantum chemical indices: the net charge of the atom N1, the net charge of the atom O16, the torsional angle of atoms C10 C9-N8-C4, the interatomic distance between atom C7 and the center of phenyl plane C9-14 (PhA), is quite well-matched. Based on these results, an interactive pattern between 3-methylfentanyl derivatives and opioid receptors was suggested; CONCLUSION: Not only are the results of neural networks superior to those of PLS method but they also provide accurate predictions of the activity of the compounds and also combine the PLS method with neural networks. PMID- 7771192 TI - Assay of metoprolol and alpha-hydroxymetoprolol in human urine by reversed-phase liquid chromatography with direct-injection. AB - AIM: To develop an HPLC method with direct injection for the simultaneous determination of metoprolol (M) and alpha-hydroxymetoprolol (HM) in human urine. METHODS: Urine (200 microliters) was diluted with eluate and injected into the chromatograph. Samples were separated on an ODS column by isocratic binary elution and monitored by fluorescence detection. RESULTS: No potential interfering peaks were identified. M and HM gave rapid elution and baseline resolution. The linear curves of both analytes ranged between 0.2 and 100 mg.L-1. The response sensitivity was approximately 0.1 mg.L-1 and the coefficients of variation in the assay were within 8% for both compounds. A typical application in oxidation phenotyping was presented for one healthy volunteer who received 100 mg of oral metoprolol. CONCLUSION: The method can be used for the investigation of genetic polymorphism of metoprolol oxidation in the large populations. PMID- 7771194 TI - Effect of colchicine on hepatic glycosaminoglycan metabolism in mice infected with Schistosoma japonicum. AB - AIM: To study the effect of colchicine on hepatic glycosaminoglycan (GAG) metabolism in mice infected with Schistosoma japonicum. METHODS: The amount of GAG was measured in the liver of mice infected with Schistosoma japonicum for 6 16 wk and treated with colchicine. RESULTS: Six weeks after infection, the GAG content of infected mice's livers and uninfected control was 14 +/- 2 micrograms/g liver and 4 +/- 1 microgram/g liver, respectively. The GAG content reached a peak about 6 times of the normal level in the 10th wk after infection, being 56 +/- 9 micrograms/g and 10 +/- 1 microgram/g for infected and uninfected mice respectively, and then declined. Treatment of infected mice with colchicine reduced the total GAG content to 22 +/- 3 micrograms/g liver, but not suppress the GAG content below the normal level in the 10th wk. Microscopic hepatic egg granuloma. CONCLUSION: Colchicine may exerts its GAG reduction effect through the suppression of granuloma formation. PMID- 7771193 TI - Effects of nimodipine, felodipine, and verapamil on isolated human arteries. AB - AIM: To evaluate whether there might be some difference in the action modes of nimodipine (Nim) and felodipine (Fel). METHODS: Compare the inhibitory effects of Nim and Fel with that of verapamil (Ver) as a representative of phenylalklamine on norepinephrine (NE)- and CaCl2-evoked contractions of human arteries. RESULTS: In Ca(2+)-free and high K+ depolarized solution, inhibitory effects of Nim, Fel, and Ver were more potent on CaCl2-induced contractions on isolated human arteries than those on NE-induced contractions. In CaCl2-induced contraction, the pD2 values for Nim, Fel, and Ver were 7.5, 7.42, 6.35 on uterine arteries; 7.38, 7.65, 7.20 on mesenteric arteries and 7.87, 9.10, 7.32 on renal arteries, respectively. Ver inhibited 2 components of NE-evoked contraction, while Nim and Fel only inhibited extracellular Ca(2+)-dependent contractions. CONCLUSION: The result indicates that Fel has a selective action on human renal arteries. PMID- 7771195 TI - Endogenous adenosine and ATP-sensitive potassium channel modulate anoxia-induced electrophysiological changes of pacemaker cells in sinoatrial node of guinea pigs. AB - AIM: To investigate the electrophysiological effects of adenosine deaminase (ADase, an enzyme converting adenosine to inosine and ammonia), 8 phenyltheophylline (8-PT, a nonselective antagonist of adenosine receptors) and glibenclamide (Gli, a potent blocker of ATP-sensitive K+ channels) on anoxic pacemaker cells of SA node. METHODS: Anoxia of pacemaker cells in SA node of guinea-pig was induced by perfused for 20 min with a modified K-H solution gassed with 100% N2 deprived of glucose. Parameters of action potentials including maximal diastolic potential (MDP), amplitude of action potential (APA), duration of 90% repolarization (APD90), maximal rate of depolarization (Vmax), rate of pacemaker firing (RPF), and velocity of diastolic (phase 4) depolarization (VDD) were recorded using intracellular microelectrodes. RESULTS: Anoxia increased MDP, APA, and Vmax and decreased VDD, RPF in a time-dependent manner. ADase 10 U.L-1, 8-PT 0.1 mumol.L-1 and Gli 10 mumol.L-1 significantly attenuated the electrophysiological changes of pacemaker cells in sincatrial node induced by anoxia. CONCLUSION: Endogenous adenosine and ATP-sensitive K+ channels may play an important role in the generation of anoxic bradycardia in guinea pigs. PMID- 7771196 TI - Determination of free digoxin in sera of 8 patients with chronic cardiac insufficiency. AB - AIM: To establish a method for the determination of free digoxin in serum for clinical use and to study the relationship between the free and total digoxin concentrations in chronic cardiac insufficiency patients receiving digoxin with different renal function. METHODS: The ultrafiltration with fluorescence polarization immunoassay was used to determine the concentration of free digoxin. RESULTS: The concentrations of digoxin standards in serum were 0.96, 1.92, and 3.84 nmol.L-1. The relative standard deviation was < 7% for intra-day and < 6% for inter-day determinations. The average recovery was 99.95 +/- 2.18%. The ratio of free/total digoxin in chronic cardiac insufficiency patients with renal dysfunction was lower than that in patients with normal kidneys (63.5 +/- 4.7% vs 75.1 +/- 3.9%, P < 0.01). CONCLUSION: The present method is simple and reliable. In these patients there is an over-measurement for total digoxin concentration, suggesting the presence of elevated endogenous digoxin-like immunoreactive substances. PMID- 7771198 TI - Effects of pineal body and melatonin on lymphocyte proliferation and dinoprostone production in rat spleen. AB - AIM: To determine the effects of pineal body and melatonin (Mel) on lymphocyte proliferation and dinoprostone production in rat spleen. METHODS: Pinealectomy (PE), lymphocyte proliferation assay and dinoprostone radioimmunoassay were used. RESULTS: A circadian rhythm of splenic lymphocyte proliferation which peaked at 22:00 was obliterated by PE in rats. PE led to an impairment of lymphocyte proliferation and an increase of dinoprostone production, which were restored by ip Mel 10 micrograms.kg-1.d-1 at 16:00 for 7 d. Mel promoted lymphocyte proliferation and inhibited dinoprostone production in intact rats. A negative correlation between the change in lymphocyte proliferation and dinoprostone production was seen. CONCLUSION: The pineal body and its main hormone Mel play a regulatory role in circadian lymphocyte proliferation which is related to dinoprostone production in rat spleen. PMID- 7771197 TI - Effects of glutamate dehydrogenase, choline oxidase, and glucose-6-phosphatase on 67Ga accumulation in lysosome. AB - AIM: To clarify the effects of the activities of hepatic enzymes in liver, hepatoma, and malignant tumor on 67Ga accumulation in lysosome. METHODS: 67Ga citrate solution was prepared from carrier-free 67Ga-citrate solution 0.08 mol.L 1 and sodium citrate solution 0.08 mol.L-1, and was injected iv 0.4 ml to the rats. Subcellular fractions of the liver were measured for radioactivity of 67Ga by a well-type scintillation counter (Aloka JDC-701). Glutamate dehydrogenase, choline oxidase, and G-6-P activities were calculated as described by Shimizu H, Ikuta S, and Baginski E, respectivily. RESULTS: 67Ga radioactivity in normal liver lysosome (55%) was significantly higher than those in hepatoma AH 109A (32%) and Yoshida sarcoma (18%). Glutamate dehydrogenase activities were 1830 +/- s 320 U.L-1 in normal liver while 23 +/- s 6 U.L-1 in hepatoma AH 109A, and 7 +/- s 2 U.L-1 in Yoshida sarcoma. Choline oxidase activities were 46 +/- s 10 U.L-1 for normal, 25.0 +/- s 0.4 U.L-1 for hepatoma AH 109A, and 2.0 +/- s 0.4 U.L-1 for Yoshida sarcoma. G-6-P activities were 2550 +/- s 180 U.L-1 in normal, 84 +/- s 14 U.L-1 in hepatoma AH 109A, and 78 +/- s 13 U.L-1 in Yoshida sarcoma. CONCLUSION: Lysosome of normal rat liver in which hepatic enzymes work actively played a major role in the tissue concentration of 67Ga, but the role diminishes with the neoplastic transformation into hepatoma. The lysosome of Yoshida sarcoma does not play any role in 67Ga accumulation because it does not possess any features of liver. PMID- 7771199 TI - Phencyclidine receptors in brain and spinal cord of spontaneously hypertensive rats aged 4-16 wk. AB - AIM: To study the relationship between the density of phencyclidine [1-(1 phenylcyclohexyl)piperidine hydrochloride, Phe] receptor binding sites in brain and thoracic spinal cord (T4-6) and the development of hypertension in spontaneously hypertensive rat (SHR). METHODS: The density of Phe binding sites was determined by autoradiography using [3H]Phe in 4-, 8-, 12- and 16-wk-old rats. RESULTS: There were fewer Phe binding sites in the hippocampus and dorsal horn of thoracic spinal cord of SHR at 12 and 16 wk (P < 0.01), when hypertension has established; while at 4 wk of age, before the development of hypertension, more Phe binding sites were found in SHR. As blood pressure began to rise at 8 wk, SHR had more Phe binding sites in hippocampus vs WKY, but no difference was seen between 2 strains in the dorsal horn of thoracic spinal cord. CONCLUSION: Phe receptors might be involved in the genesis of SHR hypertension. PMID- 7771200 TI - [A simple method for estimating half-life of drugs obeying Michaelis-Menten elimination kinetics]. AB - AIM: To establish a simple method for estimating half-life of drugs obeying Michaelis-Menten elimination kinetics. METHODS: A linear relationship is sketched between elimination half-life and drug concentration in blood that obey Michaelis Menten elimination kinetics. A simple method is proposed to draw a regression line of blood drug concentration vs time after a single bolus intravenous injection. RESULTS & CONCLUSION: The elimination half-life can be read from the regression line. The method can also be used to estimate the time required for the plasma concentration of a drug to decrease any fraction. PMID- 7771201 TI - Proceedings of the Fifth China-Japan Joint Meeting on Pharmacology (CJP-94), 1994 Oct 28-31 Hangzhou, China. Abstracts. PMID- 7771202 TI - [Lumbar spinal stenosis. Significance of neurophysiologic tests]. AB - The authors review Lumbar Spinal Stenosis discussing the diagnostic criteria, the etiopathogenesis, and clinical manifestations. Imaging and neurophysiological investigations are also discussed. EMG, Sensory Evoked Potencials and Motor Stimulation are described stressing their role in differential diagnosis. The therapeutic approach is briefly commented. PMID- 7771203 TI - [Neurologic paraneoplastic syndromes]. AB - Some neurologic syndromes are often associated with neoplasm, as a paraneoplastic disorder. Among them, namely, subacute cerebellar degeneration, sensory neuronopathy, dermatomyositis/polymyositis, Lambert-Eaton myasthenic syndrome and subacute motor neuronopathy, prove sooner or later to be harbouring a neoplasm, therefore a thorough clinical evaluation should be carried out to identify the primary tumour site. The AA present a brief review of these neurologic syndromes, illustrating the first three mentioned with clinical cases. A reference is made to the immunological associated aspects and their clinical importance. PMID- 7771204 TI - [Sleep, depression, and antidepressive treatments (1)]. AB - Sleep research in depressive disorders has advanced considerably in the last two decades. In this review we highlight the different facets of this research, including neurophysiological descriptions of sleep disturbances in depression and data regarding the effects of antidepressant treatments on sleep. The available information is discussed taking into consideration a possible pathogenic role of certain sleep changes in depression, as assumed by several theoretical models. The scope of these models and their explanatory power are briefly analysed. Some comments are made on conceptual and methodological problems in the field of sleep research in psychiatric disorders. PMID- 7771205 TI - [Evaluation and quality assurance of mental health services]. AB - Evaluation and quality assurance are primary issues in mental health care today. An up-date of current knowledge and experience in this domain is the main objective of this paper. The authors begin by describing the reasons that justify the current interest in this subject, defining concepts and summarizing the most relevant historical antecedents. This is followed by a discussion of the main methodological aspects--basic concepts (particularly those related to structure, process and outcome), specific issues in mental health service evaluation, difficulties in the implementation of evaluation procedures and choice of indicators. Special attention has been given to the most recent developments in mental health service evaluation--namely those related to assessment needs and quality of life measurement. The impact of the regular use of evaluation instruments on the transformation and development of mental health services is also discussed. The contributions that can be made by evaluation procedures to the definition of mental health policies and to overcome mental health service deficiencies are stressed. Finally, the necessity of joining efforts in order to generalize the use of evaluation and quality assurance instruments in the mental health services in this country is pointed out. PMID- 7771206 TI - [Prenatal diagnosis of congenital cardiopathies. Dissemination and education]. PMID- 7771207 TI - [Fetal arrhythmia. A case load of 4 years and a half]. AB - In a 4 1/2 year period fetal, echocardiographic studies were performed on 1600 fetuses. In 55 with arrhythmia, 44 had supraventricular ectopic beats, resolved in all, and none had heart disease. Sustained arrhythmias occurred in 11 fetuses. Atrial flutter was present in 3 all with heart disease (Ebstein disease, right atrial tumour and WPW diagnosed after birth). Another 3 fetuses had supraventricular tachycardia (SVT), all with a normal heart. In the bradycardia group, 2 had complete heart block (CHB) associated with AVSD; 2 sinus bradycardia and one had non conducted atrial ectopic beats. Digoxin was the first choice drug for tachyarrhythmia therapy; association with Verapamil, Flecainide, Quinidine and Procainamide was used in 4 of the 6. One fetus with CHB received Orciprenaline with no results. Atrial flutter resolved or improved; in SVT 2 fetuses converted to sinus rhythm and one died in utero. All fetuses with CHB died in cardiac failure. Mortality was 27% (3 cases) in utero and global 36%. In our experience most fetal arrhythmias (90%) were transitory ectopic beats or non lasting bradycardia in normal heart and did not trigger other kinds of arrhythmias. In sustained arrhythmias, heart failure and heart disease had a negative effect on prognosis. PMID- 7771208 TI - [Mother-child transmission of immunoglobulins G]. AB - The placental transfer of immunoglobulins is made by active transport and only IgG class of immunoglobulins is transferred. In a full-term gestation IgG concentration is usually higher in the cord serum than in the mother serum. It has been shown that the ratio of cord/maternal IgG is higher when maternal IgG values are low. A series of 44 mother-child pairs from the north of Portugal were studied. Quantitative determination of IgG in all sera was made by single radial immunodiffusion and results were expressed in milligrams/deciliter (mg/dl). In the first 48 hours after delivery, mothers were interviewed and clinical, social and demographic data were collected. In 35 pairs, cord IgG exceeded the corresponding maternal concentration. The ratio of cord/maternal IgG ranged from 0.75 to 2.86 (mean 1.27). From all studied variables only maternal IgG concentration and age were correlated with that ratio. Transplacental concentration (ratio of cord/maternal IgG) was higher for lower levels of maternal IgG. Significant contribution of maternal age did not stand when a woman with extreme values of IgG and age was withdrawn from the analysis. Values found for this series of Portuguese mother-child pairs were similar to those found for other caucasian populations and are in agreement with current proposed models for placental transfer of IgG. PMID- 7771210 TI - [Diagnostic criteria for primary dyslipidemia]. AB - The accurate treatment of a dyslipidaemia is based on correct diagnosis. Together with the laboratory values. A good clinical interview, focusing on the family history, is the bases for a good diagnosis strategy. The author schematze the rules of etiological diagnosis of inherited defects of lipid metabolism. PMID- 7771209 TI - [Hospital prevalence of kidney failure. Consequences and reflections for the planning of nephrology services]. AB - A prospective prevalence study of Renal Failure (RF) in inhospital patients (creatinine > = 1.7 mg/dl) was carried out during March 1994, in two hospitals covering well defined and mutually exclusive populations. Cases were selected by screening all urea and creatinine blood tests performed in both laboratories, and registered in an individual form for daily follow-up of their nephrologic outcome. We registered 242 RF cases among 3525 patients admitted (6.8%), with an A.R.F. prevalence of 5.2%, 46% of all patients had a serum creatinine > 3 mg/dl and 71% were older than 65 years. In 55% RF was acquired inside the hospital. The most frequent cause of A.R.F. was pre-renal failure with 37%, followed by 32% of ischemic acute tubular necrosis and 13% toxic ATN. Nephrology was consulted in only 29% of all hospital RF cases. Only 17% of the RF patients were submitted to dialysis procedures, overall mortality was 31%, and 30% had normal renal function at discharge. Our results provide a data base to rethink the organization, staffing and role of nephrology departments inside general hospitals. PMID- 7771211 TI - [Primary lymphoma of the lung]. AB - Primary lymphomas of the lung are rare neoplasias that can be easily diagnosed when enough tissue is available, but are easily mistaken for lung carcinomas or mesotheliomas on clinical evaluation. Two surgical cases are described with reference made to their morphological and immunohistochemical characteristics. PMID- 7771212 TI - [Hemangiopericytoma]. AB - A case of hemangiopericytoma located in the left upper thigh is presented. The literature is reviewed, particularly the clinical aspects and reference is made to arteriography and preoperative embolization. PMID- 7771213 TI - Minimally invasive neurosurgery II. Proceedings of the 2nd meeting on endoneurosurgery. Marburg, Germany, January 30-February 1, 1992. PMID- 7771214 TI - Minimally invasive endoscopic neurosurgery--a survey. AB - In 1989 we introduced "endoscopic stereotaxy" as a new operative procedure into neurosurgery. This technique was first scheduled to optimize stereotactic biopsy. In its further development it proved to be effective for other indications. We choose the term "Minimal Invasive (Endoscopic) Neurosurgery (MIEN)" for these interventions. Minimal invasive endoscopic techniques are applied preferably for diagnostic and therapeutic interventions on preformed or pathological cavities of the central nervous system. The indications are, endoscopic-stereotactic biopsy of space-occupying lesions, ventriculoscopy and endoscopic ventriculostomy in diagnosis and treatment of hydrocephalus, endoscopic evacuation of cystic space occupying lesions, endoscopic evacuation of intracerebral haematoma, endoscopic evacuation of septated chronic subdural haematoma, endoscopic evacuation of subacute or chronic brain abscesses, endocavitary syringostomy. Our results with minimal invasive endoscopic interventions for different indications are encouraging when compared to conventional microsurgical techniques. We have performed more than 300 minimal invasive endoscopic interventions. The mortality rate was below 1%, the operative morbidity was below 2%. PMID- 7771216 TI - Epiduroscopy and spinaloscopy: endoscopic studies of lumbar spinal spaces. PMID- 7771217 TI - Operative spinal endoscopy: stereotopography and surgical possibilities. AB - The polyprojective microstereotopography of spinal canal structures at the cerebello-spinal, cervical, thoracic, lumbosacral and cauda equina levels on 20 fresh cadavers is presented using flexiscopes 3.7-3.9 mm diameter. This is possible due to the space between spinal cord-vertebral canal which is about 10 mm at all levels. This also allows one to insert the endoscopic tube by posterior or interradicular approach. The subdural and subarachnoid endoscopic examinations have been performed through small foraminotomic openings with resection of the base of the spinous process. The anterior and posterior roots, the spinal cord, dural root sleeves, cerebellar tonsils, orifice of the IV ventricle, vertebral artery and its lower branches can be visualised. On the stereotopographic basis the first operations in patients with severe spinal cord injury (detection of multilevel cord compression, removal of massive subarachnoid bleeding), syringomyelia and haemorrhage into the IV ventricle (clot removal by the ascending cervical route) were undertaken. More than 10 real and probable indications for operative spinal endofiberoscopy are discussed. PMID- 7771215 TI - Endoscopic stereotactic treatment of brain abscesses. AB - Treatment of brain abscess is still a subject of controversy. Craniotomy with primary extirpation and resection of the abscess membrane, burrhole craniotomy with puncture or insertion of a drain, marsupialization, or stereotactic aspiration are different therapeutic approaches. As a consequence of our experiences and results with neuro-endoscopic interventions we have introduced endoscopic stereotactic techniques in brain abscess treatment. Seven patients with brain abscesses were operated on stereotactically using an endoscope. In all cases the abscess contents were aspirated, while the abscess membrane was left in situ. The patients received postoperative antibiotic therapy according to microbial diagnosis. The longest follow-up period was 48 months. Six patients showed a marked improvement of neurological deficit after treatment. One patient died from sepsis caused by a bacterial endocarditis. The results emphasize that endoscopic stereotactic technique as a minimally invasive neurosurgical method can also be used for treatment of brain abscess. PMID- 7771218 TI - Technology assessment of endoscopic surgery. AB - Endoscopic surgery is considered a milestone in the evolution of surgical technique in nearly all fields of surgery. However, the inappropriate use of the new technology in medicine has also been heavily criticised. Systematic technology assessment of endoscopic surgical techniques is mandatory to prove the real benefits and complications, so defining the indications for their appropriate use. This article describes methods of technology assessment suitable for endoscopic techniques with emphasis on relevant endpoints for surgeons and patients. The general stages of a comprehensive technology assessment include: 1. feasibility (safety and technical performance) 2. efficacy (patient benefits in pioneering places) 3. effectiveness (patient benefits in average hospitals in the community as a whole) and 4. economic evaluation (cost-benefit analyses). We used the example of laparoscopic cholecystectomy to describe the methods of technology assessment. A cohort study on 500 patients revealed that laparoscopic cholecystectomy is as safe as the conventional standard open technique. The results on efficacy strongly support the hypothesis of more comfort and less trauma with the endoscopic technique. Major endpoints evaluated were postoperative pain, convalescence, fatigue and quality of life. Data on effectiveness and economics are still in a "premature" state and should be the subject of further analyses. It is concluded, that other disciplines such as neurosurgery should evaluate their endoscopic surgical techniques according to the rules of technology assessment outlined in this paper. PMID- 7771219 TI - Fundamentals of laser science. AB - The importance of laser application in minimal invasive neurosurgery is emphasized. Physical fundamentals of laser energy are described, and the physics of laser tissue interactions are discussed. Different surgical laser types as the carbon dioxide laser, the argon laser, and the Nd:YAG laser as well as the application mode (contact versus non-contact mode) are compared according application. The main indication for the use of laser in minimal invasive neurosurgery is cutting, coagulation, vaporization, and interstitial irradiation. PMID- 7771220 TI - Magnetic field guided endoscopic dissection through a burr hole may avoid more invasive craniotomies. A preliminary report. AB - The neuroendoscope, coupled with radiofrequency or laser dissecting tools, can effectively resect obstructing membranes, biopsy and debulk tumor, and evacuate hematomas when the pathology is within the ventricular system. This less invasive approach through a burr hole usually avoids craniotomies. When the abnormal condition is within parenchyma or in the presence of opacifying bloody fluid, landmarks are not recognizable and the neurosurgeon quickly becomes disoriented. A more extensive craniotomy or a stereotaxic-guided procedure is then necessary. We describe our preliminary experience with a geographic intracranial navigation system using realtime measurement of electromagnetic field strength in multiple planes to precisely indicate the position of the tip of the endoscope. A transmitting antenna is positioned beneath the patient's head. A 1.5 centimeter cubic antenna receiver is mounted upon a lenscope with instrument channel. The scope is guided into the surgical field after insertion through a burr hole. A square wave pulsed electromagnetic field measurement is made 140 times per second with correction for the earth's magnetic field once per second. Intracranial position data for the dissecting tip in regard to X, Y, Z, pitch, roll and yaw are output to a digitized computer map of the patient's MRI or CT scan. Also displayed on the computer screen is the video image from the endoscope. The neurosurgeon thus has simultaneous realtime geographic and near-field localization as he dissects. Electromagnetic field guided accuracy is within 2.0 mm inside the allowable 24 inch working sphere about the patient's head. Coupled with near-field video precision, accuracy is within 1 mm of recognizable dissection planes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771221 TI - New kinds of microneuroprotectors for microsurgery and endoscopy of cerebellopontine angle neurovascular decompression. AB - New microsurgical devices for neurovascular decompression--microneuroprotectors (MNP)--are described. Four constructive kinds of MNP have been developed according to topographic peculiarities of pathological neurovascular contacts. The hydrodynamic and biological testing of MNP has been concluded. The methods of microsurgical and endoscopic techniques of MNP insertion on the cranial nerves or posterior fossa vessels are reported. PMID- 7771222 TI - A computer assisted toolholder to guide surgery in stereotactic space. AB - A computer assisted toolholder, integrated with an anatomical graphic 3-D rendering programme, is presented. Stereotactic neuroanatomical images are acquired, and the same reference system is employed to represent the position of the toolholder on the monitor. The surgeon can check the orientation of different approach trajectories, moving the toolholder in a situation of virtual reality. Angular values expressed by high precision encoders on the five joints of the toolholder modify "on line" the representation of the configuration of the toolholder within the three dimensional representation of the patient's anatomy. PMID- 7771224 TI - A multipurpose cerebral endoscope and reflections on technique and instrumentation in endoscopic neurosurgery. AB - We discuss our experiences concerning our cerebral endoscope with reflections on various techniques used since 1986. During this time we have had experience with four prototypes. This minimal invasive procedure has been successful to a certain extent both in paediatric and adult patients, stereotactically and by freehand method or both. Further modification for flexibility and manipulation of the optic element is under development. PMID- 7771223 TI - Ultrasound guided endoscopic neurosurgery--new surgical instrument and technique. AB - For minimal invasive endoscopic neurosurgery, a mini-caliber endoscope equipped with a useful working channel and its guidance system is basically essential. We developed the device for ultrasound guided endoscopic neurosurgery. A minicaliber fiberscope with an outer diameter of 3.4 mm equipped with 2.5 mm of working channel for forceps, suction, and coagulation probe was developed. A 5 MHz phase arrayed 12 mm ultrasound probe was used as guidance system. A fixation device for the mini-caliber fiberscope and ultrasound probe was also constructed. The surgical procedure is very simple, and can be performed through a 2 cm burr hole. Real-time and a directly visualized image might provide more safety and reliability during brain surgery. PMID- 7771225 TI - Endoscopic anatomy of the third ventricle. AB - 42 cadaver brains in situ were examined endoscopically to work out topographical anatomical landmarks for orientation. The endoscopic route from the chosen precoronal trepanation point to the defined ventricular landmarks has been measured in 22 cases. The identification and measurements of the anatomical landmarks are helpful for safe and atraumatic endoscopical navigation within the ventricular system. Furthermore this article describes and discusses cerebral lesions during ventriculoscopy. PMID- 7771226 TI - Endoscopic anatomy of the ventricles. AB - The endoscopic view offers a new anatomical dimension to the neurosurgeon. The fact makes it basically necessary to study the topographic anatomy under endoscopic conditions. In this paper attention was drawn to the ventricles because they are the most common region of clinical application. In 25 specimens neuroendoscopic explorations of the ventricles have been done. The dissections have been carried out through one- and two burr hole approaches (two working endoscopes at the same time). The instrumentation includes rigid 4 mm and 6 mm endoscopes. The procedures have been documented by continuous video recording and parallel photography. PMID- 7771227 TI - "Stereology" of intracranial lesions. AB - Endoscopy of the intracranial space requires a new understanding of the anatomy and pathology of pertinent structures. This meets with the new development of imaging methods which equally require three dimensional interpretation of intracranial pathology. The stereological arrangement of intracranial lesions is examplified on three neuropathological conditions: brain tumours, territorial infarction and mass displacement. PMID- 7771228 TI - Endoscopic diagnosis and treatment of para- and intra-ventricular cystic lesions. AB - Different cystic lesions can be located in or around the ventricular system, eventually causing hydrocephalus. Twenty-one patients are described where endoscopic intervention, mainly large fenestration towards the ventricular cavity, has been performed. This treatment can sometimes replace open surgery or extracranial shunting. Most rewarding are the arachnoid and ependymal intra- and paraventricular cysts. With careful and adequate endoscopic technique this procedure is safe and much less invasive than other methods described. PMID- 7771230 TI - Neuroendoscopic third ventriculostomy. A practical alternative to extracranial shunts in non-communicating hydrocephalus. AB - The outcomes in 103 patients who have undergone third ventriculostomy for non communicating hydrocephalus at our institution form 1978-1994 have been analysed. The group has been sub-divided by age, cause of hydrocephalus and whether the third ventriculostomy was the initial definitive procedure or whether progression of their hydrocephalus had been arrested for a long time (usually years) by an extracranial shunt prior to third ventriculostomy. At the time of shunt malfunction (usually blockage) a third ventriculostomy was performed if the anatomy was, or could be made suitable for the safe performance of the procedure. Third ventriculostomy under the age of 6 months was successful in only 8 of 25 patients. Seventeen patients in whom the onset of hydrocephalus was under the age of six months and the ventriculostomy was performed between 6 months and 18 years, 8 were successful. Sixteen of these had had previous long term shunts. In 40 patients in whom the onset of hydrocephalus was over the age of 6 months and the ventriculostomy performed after the age of 19 years, 32 were successful. In 28 patients over the age of 20 years, 13 had previously been shunted and in 8 of these the procedure was successful. In 15 patients not previously shunted, 9 ventriculostomies were successful. Three failed, 2 died before evaluation could be done and one was lost to follow-up. There were no deaths caused by the procedure. Two patients suffered from a hemiparesis, (1 transient) 1 patient suffered mid-brain damage. There were 2 subdural effusions. Two patients had infections, 1 superficial and 1 a ventriculitis. PMID- 7771229 TI - Stereotactic techniques for colloid cysts: roles of aspiration, endoscopy, and microsurgery. AB - Stereotactic surgical techniques were used to manage 25 consecutive patients with colloid cysts of the third ventricle. All patients had stereotactic aspiration as the initial procedure; it was successful in 13 (52%). In patients in whom aspiration failed, endoscopic visualization of the cyst and attempted removal, or microsurgical cyst resection via a transcortical approach was performed. Three elderly patients did not have a second procedure and were shunted. The computed tomographic appearance of a hypodense or isodense cyst indicates low-viscosity contents and predicts successful stereotactic aspiration. Stereotactic microsurgery is used in hyperdense cysts, or in those which cannot be aspirated. PMID- 7771231 TI - Endoscopic surgery of traumatic intracranial haemorrhages. AB - The results of endofiberscopic removal of traumatic intracranial haematomas and hygromas in 180 patients are analysed. Peculiarities of the surgical techniques using flexiscopes and original devices in epidural, subdural, intracerebral, intraventricular haemorrhages of various consistencies, size and location are reported. A technique of the trephination access and delayed cranioplasty for endoscopic removal of extensive subdural and intracerebral haematomas is presented. Indications, contra-indications for endoscopic haematoma surgery, advantages, disadvantages, failures of the techniques are discussed. PMID- 7771232 TI - Endoscopic stereotactic interventions in the treatment of brain lesions. AB - Image-guided stereotaxis is an accurate and safe method of directing therapy to target volumes defined in two-dimensional (2D) multiplanes or three-dimensional (3D) perspectives using computer reconstruction of image data. The major limitations of stereotactic techniques are a lack of intraoperative visualization and direct monitoring of the procedures, and changes of intracranial coordinates after decompression of cystic lesions or aspiration of cerebrospinal fluid in the management of intraventricular lesions. Endoscopic laser stereotaxis (ELS) involves integration of rigid-flexible endoscopy and Nd-YAG laser to 3D-2D multiplanar image-guided stereotactic procedures. The major advantages of ELS include: minimally invasive (burrhole or small craniotomy surgery), direct intraoperative visualization, hemostasis, evacuation or resection assessment, and wide exploration of intracranial cavities or ventricles. ELS has been used in the management of 152 clinical cases including biopsy, aspiration, resection and internal decompression of deep and subcortical intracranial lesions, and different types of fenestration procedures. Image-guidance combined with endoscopic techniques may offer a safe, accurate alternative to conventional neurosurgical procedures in treating small solid, cystic, and intraventricular lesions as well as fenestration procedures. PMID- 7771233 TI - Stereotactic endoscopic resection of angiographically occult vascular malformations. AB - Total resection of angiographically occult vascular malformations was performed in four patients using stereotactic open-system endoscopy. The lesions were relatively small but localized deep in the brain or involving eloquent cortex. Fiber-guided YAG laser coagulation was efficient for haemostasis and no significant complication was seen in any case. Endoscopic stereotactic laser surgery by open-system endoscopy is considered a safe and promising treatment for small AOVM's located in deep or eloquent neural structures. PMID- 7771234 TI - [Uroflowmetric nomogram in the adult population of Canary Islands]. AB - In order to know the uroflowmetric values of our healthy population, a uroflowmetry was made to 214 healthy subjects of both sexes. 75% of our group of volunteers collected mictional volumes under 300 ml. with no differences either by age or sex. The corresponding nomograms, in the form of percentile, for peak and mean flow in both sexes, were created. We found a progressive increase of peak and mean flow values with regard to mictional volume. Time to peak flow is shorter in women than in men. Volume at peak flow represents under 50% of total mictional volume. No significant differences in the uroflowmetric data of our healthy population and those from Anglo-Saxon authors was found. PMID- 7771236 TI - [Occupation and bladder tumor. Results of a study of incident cases]. AB - Presentation of the results from the occupation analysis in a study of incident cases of vesical tumour over a 16-year interval (1975-1991) conducted in La Rioja Autonomous Community. Out of the 557 cases identified, occupation was found in 455, 151 of them are farmers (33.18%), 71 are in the industrial sector (15.60%), and 233 in the services sector (51.20%). Percentage of individuals affected by production sectors according to 1985 data are 1.22% farmers, 0.3% industrial sector and 0.6% services sector. PMID- 7771235 TI - [Clinical features, diagnosis, and treatment of tumor lesions arising in the adrenal gland]. AB - Between 1981 and 1993, 14 patients with tumoral adrenal disease were diagnosed and treated in the Urology Services of both Hospitals. Nature of the adrenal disease was functional in 8 patients (two carcinomas and six pheochromocytomas) and non-functional in the rest (three carcinomas, two adenomas and one myelolipoma). Reference is made to the clinical manifestations and laboratory tests related to hormonal activity, depending on whether the tumour is functional or non-functional, chromaffin or non-chromaffin. Patients with functional carcinomas had Cushing's syndrome, with very clear virtilization signs. Urine 17 hydroxycorticosteroid, 17-cetosteroides and cortisol were all increased, same as plasma cortisol. Patients with pheochromocytomas had hypertension and headaches (six patients), sweating (five patients), anxiety (four patients) and loss of weight (two patients). All of them had increased urine vainillylmandelic acid and catecholamines. Clinical signs and symptoms of non-functional tumours were related to bulk growth and size (in the three carcinomas), and sometimes was highly anodyne, or even absent (in the two adenomas and the myelolipoma), the cause of discovery being accidental during an ultrasound examination. An analysis is made of the different imaging diagnostic procedures performed, such as IVU (performed in 13 patients) with a 38.4% resolutory power; ultrasound (performed in 11 patients) with an 81.8% resolution; CAT (performed in 6 patients) with a 100% resolution capacity and arteriography (performed in 3 patients) with a 100% resolution power, although patients had previously undergone ultrasound and CAT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771237 TI - [Vestibular approach in urinary incontinence in women. Original technic. Experience. Results]. AB - Presentation of an original technique to treat S.U.I. in women. This technique contains in itself many others, both in terms of the conceptual anatomical base on which it is inspired, and in the possibilities of its surgical application. Lisfranc's approach, supra-meatic and infra-clitoridean, allows to section both the pubo-urethral ligament and Colles fascia thus reaching into the Retzius. It makes possible the use of solid anatomical elements (pelvian fascia, elevator, urethro-vaginal septum, etc...) thus allowing to suspend the pelvian base from fascia ligaments or from the abdominal wall muscles. Sixty patient who had simple S.U.I. received treatment, with a 95% efficacy index based on the evaluation of the urodynamic, bacteriological and clinical studies. We conclude with an evaluation on the validity of the results obtained by emphasizing the high efficacy index, simplicity, low morbidity and short hospital stay. PMID- 7771238 TI - [Endoscopic internal urethrotomy guided with transrectal echography]. AB - Internal urethrotomy is the endoscopic technique most commonly performed in order to resolve urethral stenosis. This paper describes a new technique which associates transrectal ultrasound to internal endoscopic urethrotomy for the resolution of unsurmountable stenosis of the urethra. Presentation of 6 cases, with a 100% success rate. The authors believe that the association of transrectal ultrasound with internal endoscopic urethrotomy is a simple technique, and very useful for the resolution of unsurmountable stenosis of the urethra. PMID- 7771239 TI - [Extracorporeal shockwave lithotripsy in patients with urinary diversion]. AB - Presentation of a review on nine patients (10 renal units) with urinary by-pass and renoureteral lithiasis who underwent shock wave extracorporeal lithotrity in our hospital. The justification for the by-pass was an infiltrant vesical tumour in 6 patients, myelomeningocele in 2, and vesicourethral trauma in the remaining one. All cases were being treated for a Bricker-type by-pass except the last one (bilateral ureterosigmoidostomy). Outcome of treatment was: absence of residual lithiasis in 6, minimal residues in 1 (2 renal units), failure in 1. The remaining patient suffered anaphylactic shock induced by the latex in the ureteral catheter placed prior to lithotrity which caused the patient's death. PMID- 7771240 TI - [Enzyme-induced masculinization]. AB - Contribution of two cases of congenital adrenal hyperplasia by blockade in the 21 hydroxylase enzyme synthesis. Diagnosis was reached from the clinical signs and symptoms (virilization syndrome), and was confirmed by radiological and laboratory tests. Hormone treatment was done with hydrocortisone and fludrocortisone, but surgical correction of external genitalia was required to improve cosmetic appearance. PMID- 7771241 TI - [Bilateral primary ureteral endometriosis]. AB - Exposition of a new case of primary bilateral ureteral endometriosis, a very infrequent condition where early diagnosis before treatment is difficult since no other endometrial foci are found at either the uterus or ovary level or any sites. This condition has an enormous clinical significance because in a very short interval and in a silent manner can cause complete and irreversible damage to the upper urinary tract. The article explains the clinical characteristics of the disease, and discusses the diagnostic procedures available which are generally insufficient. The importance of the histological study is emphasized, and the surgical technique and its complications are described. Also, a literature review is included. PMID- 7771242 TI - [Necrosis of undescended testis caused by incarcerated inguino-scrotal hernia in a newborn]. AB - Presentation of an uncommon case referring necrosis of an ectopic inguino-femoral testis caused by an incarcerated inguino-scrotal hernia in a 15-days old baby with a permeable peritoneum-vaginal process. In this case, the hernial incarceration episode was responsible for the organ necrosis due to an haemorrhagic infarction. Orchiectomy was performed, and the pathoanatomical diagnosis was testicular haemorrhagic infarction. Review of the pathogenic mechanisms of testicular ectopia, associated anomalies and likely acute complications: torsion, hernial strangulation, traumatism and infections simulating acute abdomen which, in spite of their rarity, may have serious consequences with regard to testicular viability. PMID- 7771243 TI - [Small cell undifferentiated carcinoma of the urinary bladder: report of a case]. AB - Small cell carcinoma of the urinary bladder is an uncommon tumor. We report a case in a 80 year-old man. The patient had gross hematuria. Urographic and echographic studies revealed a sold tumor on the right wall of bladder. Pathologic study revealed a deeply invasive tumor composed of small, uniform, round and spindled shaped cells with hyperchromatic nuclei and numerous mitosis. The immunohistochemical reaction was positive for Neuron Especific Enolase and Keratin. No metastasis were found at clinical stating (T2 No Mo). We discuss the differencial diagnosis, prognosis and histogenesis of this tumor. PMID- 7771244 TI - [Scrotal verrucous carcinoma]. AB - Cancer of scrotum is of interest, despite its relative infrequency, because of its historical importance (was the first known occupational cancer) and also of its aggressive behavior. We report a rare case of verrucous carcinoma in a 67 years old man, without recrudescence six months after surgical treatment. PMID- 7771245 TI - [The calvary of biomedical literature]. PMID- 7771246 TI - Lipid peroxides and related radicals in clinical medicine. PMID- 7771248 TI - Tissue iron overload and mechanisms of iron-catalyzed oxidative injury. AB - Tissue iron overload causes clinical syndromes that involve the heart, liver, and pancreas. While tissue iron uptake occurs by both transferrin-dependent and independent processes, tissue uptake in the iron overload syndromes occurs predominantly via transferrin-independent mechanisms. Increased redox-active iron present in hemeproteins and the cytosolic iron pool can catalyze oxidative damage to lipids, proteins, and nucleic acids, either by oxyradical dependent or independent mechanisms. Iron-catalyzed injury results in damage to cell constituents, including mitochondria, lysosomes, and the sarcolemmal membrane. These mechanisms of iron-mediated damage are involved in the pathogenesis of organ dysfunction in primary hemochromatosis, transfusion-related iron overload, ischemia-reperfusion injury, and cardiac anthracycline toxicity. PMID- 7771247 TI - Mechanisms of atherosclerosis: role of LDL oxidation. PMID- 7771249 TI - Free radicals in the pathophysiology of pulmonary injury and disease. PMID- 7771250 TI - Lipid peroxides in hepatic, gastrointestinal, and pancreatic diseases. PMID- 7771251 TI - Reactive oxygen species in normal physiology, cell injury and phagocytosis. AB - Formation of free radicals and other ROS is a continuous aspect of life. Examples include the free radical intermediates which are formed by the nonenzymatic peroxidation of polyunsaturated fatty acids of membrane lipids in a destructive process and which are also formed by the enzymatic peroxidation of arachidonic acid in the biosynthesis of potent chemoattractants. Organisms cope with these reactive species by a variety of strategies that limit formation of ROS or remove cytotoxic products. Oxidative burst reactions that yield ROS provide an effective, vital process for killing invading organisms. Research on why ROS formation is impaired in phagocytic cells of people with chronic granulomatous disease has provided new insights into the complexity of the factors that prevent inadvertent activation of this destructive force. PMID- 7771252 TI - Reactive oxygen molecules in the kidney. PMID- 7771253 TI - Reactive oxygen species (ROS) and reproduction. PMID- 7771255 TI - Antioxidants and cancer: molecular mechanisms. PMID- 7771254 TI - Autoimmune and inflammatory diseases. PMID- 7771256 TI - New directions for free radical cancer research and medical applications. AB - The nitroxides are stable, low molecular weight free radical compounds which are freely membrane permeable. These properties make the nitroxides valuable for the study of and possible protection against oxidative stresses. It is becoming increasingly clear that oxidative stress is important to the pathogenesis of cancer as well as to the development of treatments for cancer. Several nitroxides have been shown to interrupt the toxicity of oxidative stress with the protection against H2O2 toxicity and possibly ischemia/reperfusion injury being of primary importance. With respect to radiation, the nitroxides have afforded both in vitro and in vivo protection. The redox activity of the nitroxides may allow for the differential activity of these agents in normal versus tumor tissues. Further study of these compounds may yield a nitroxide with clinical applications as well as provide insight into the mechanisms of radiation cytotoxicity. Finally, the nitroxides have allowed us to explore the mechanisms of action of several chemotherapeutic agents. Understanding these processes is important to the process of ameliorating the toxicity of therapies and to the rationale design of future agents. PMID- 7771257 TI - Shock and multiple organ failure. PMID- 7771258 TI - Role of nutrients in the cause and prevention of oxygen radical pathology. PMID- 7771259 TI - Free radical mechanisms for chromosomal instability in Bloom's syndrome. PMID- 7771260 TI - Involvement of free radical mechanism in the toxic effects of alcohol: implications for fetal alcohol syndrome. PMID- 7771261 TI - 21-Aminosteroids ("lazaroids"). PMID- 7771263 TI - Interactions between vitamin E, free radicals, and immunity during the aging process. PMID- 7771262 TI - The potential of gliclazide, a sulphonylurea to influence the oxidative processes within the pathogenesis of diabetic vascular disease. AB - The clinical studies have demonstrated that patients showed significant improvements in their oxidative status after 3 months treatment. This improvement in oxidative status which was associated with a reduction in platelet reactivity, remained constant for the rest of the study period. The effect was independent of glycaemic control. The demonstration of a benefit to clinical vascular disease has proved difficult to achieve in all studies of non-insulin dependent diabetes. This is due to the multifactorial nature of complications and the long duration of disease required before microvascular complications such as retinopathy became apparent. The Japanese Diabetic Retinopathy Program24 studied the progression of retinopathy over a 5 year period comparing Gliclazide with other sulphonylureas and with placebo. The study suggested that with equivalent metabolic control there was a trend towards a lower rate of deterioration of retinopathy and a significantly lower incidence of pre-proliferative retinopathy in the group receiving Gliclazide compared with patients receiving other sulphonylureas or placebo. There is little comparative evidence on the effect of specific sulphonylureas on large vessel disease. Although improvement in parameters of hyperglycaemia is associated with an improvement in morbidity from large vessel disease. In Type II diabetes atherosclerosis coexists in the majority of patients and often predates the clinical diagnosis of diabetes. The presence of atherosclerosis which often determines the ultimate fate of the patient, further increases the level of lipid peroxidation of oxidative stress, amplifying the effects of hyperglycaemia and potentiating vascular damage. In diabetes, therefore where increased glycation and oxidation are fundamental in the pathogenesis of diabetic vascular disease agents such as Gliclazide with anti oxidant activities may have an enhanced therapeutic role. PMID- 7771264 TI - Vitamins and carotenoids--a promising approach to reducing the risk of coronary heart disease, cancer and eye diseases. PMID- 7771265 TI - Free radical scavenging and antioxidant activity of plant flavonoids. PMID- 7771266 TI - Plasma clearance and immunologic properties of long-acting superoxide dismutase prepared using 35,000 to 120,000 dalton poly-ethylene glycol. AB - Some biological properties of bovine and recombinant human Cu,Zn superoxide dismutase (bSOD and rhSOD)-poly-ethylene glycol (PEG) adducts prepared by coupling 1-9 strands of high molecular weight PEG (35,000-120,000 daltons) are compared to SOD adducts coupled with 7 or 15 strands of low molecular weight PEG (5,000 daltons). Plasma clearance after i.v. injection was measured in mice and dogs. Conjugates of bSOD with 2 strands of PEG 40,000, 3 strands of PEG 72,000 or 1 strand of PEG 100,000 demonstrated half-lives of about 36 hours in mice, whereas the half-life of a conjugate with 7 strands of PEG 5,000 was about 24 hours. A PEG-bSOD with an average of 3.3 strands of PEG 41,000 was cleared from plasma with a terminal half-life of 36 to 48 hours after intraperitoneal injection in mice. PEG-SODs prepared from bSOD and rhSOD with 3 strands of PEG 50,000 each had plasma half-lives of approximately five days in dogs. An enzyme immunoassay (ELISA) was employed to measure cross-reactivity with a rabbit antibody directed against bSOD. A series of bSOD adducts with 2 to 9 strands of PEG 35,000-120,000 were compared to PEG-bSODs with 7 or 15 strands of PEG 5,000. Attaching larger PEG strands was at least 3 times more effective in reducing antigenicity, compared to PEG 5,000. Ability to induce sensitizing antibodies was measured using subcutaneous sensitization followed by i.v. or s.c. challenge in mice. Some bSOD conjugates with either 7 or 15 strands of PEG 5,000 induced sensitization reactions before the sixth challenge. Fewer than 1% of the animals tested with bSOD or rhSOD adducts with 3 or 4 strands of PEG 65,000, or 3 strands of PEG in the 30,000-50,000 molecular weight range, showed signs of anaphylaxis during six or seven challenges. In a passive cutaneous anaphylaxis test (optimized to measure mouse IgE), neither bSOD coupled to 2 strands of PEG 120,000 nor bSOD coupled to 9 strands of PEG 35,000 induced detectable antibodies against either of these PEG-bSOD preparations or against bSOD; however, the adduct with 2 strands of PEG 120,000 reacted weakly with pre-formed antibodies to bSOD. The high molecular weight PEG-bSODs tested were not immunogenic, but were weakly antigenic, compared to bSOD. PMID- 7771267 TI - Clinical trials with Dismutec (pegorgotein; polyethylene glycol-conjugated superoxide dismutase; PEG-SOD) in the treatment of severe closed head injury. PMID- 7771268 TI - A new method for detecting lipid peroxidation by using dye sensitized chemiluminescence. PMID- 7771269 TI - Chemiluminescence and the challenge to attomole detection. PMID- 7771270 TI - Evidence against malondialdehyde bound to cellular constituents in phospholipid peroxidation. PMID- 7771271 TI - Evaluation of in vivo free radical activity during endotoxic shock using scavengers, electron microscopy, spin traps, and electron paramagnetic resonance spectroscopy. PMID- 7771272 TI - Involvement of hydroxyl radicals in endotoxin-evoked shock. PMID- 7771273 TI - The role of nitric oxide in endotoxin-elicited hypodynamic circulatory failure. PMID- 7771275 TI - Photosensitized formation of 8-hydroxy-2'-deoxyguanosine by a cationic meso substituted porphyrin. PMID- 7771274 TI - In vivo evaluation of the role of neutrophil-derived free radicals in the development of endotoxic shock. PMID- 7771276 TI - Aging associated declines in the antioxidant enzymes of human testis. PMID- 7771277 TI - Lipid peroxidation in normal pregnancy and preeclampsia. PMID- 7771278 TI - Cytochrome biochemistry in sheep retina following exposure to oxygen. PMID- 7771279 TI - Cytochrome oxidase activity in the fetal sheep retina. PMID- 7771280 TI - Age-related phospholipid hydroperoxide levels in gerbil brain measured by HPLC chemiluminescence assay and their relation to hydroxyl radical stress--clinical implications. PMID- 7771281 TI - The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds related to oxidative stress as applied to the clinical chemistry laboratory. PMID- 7771282 TI - Lipid peroxidation and diabetic complications: effect of antioxidant vitamins C and E. PMID- 7771283 TI - Vascular complications of patients in Kuwait with type 2 diabetes mellitus (NIDDM) and elevated serum lipid peroxides. PMID- 7771284 TI - Vascular and cellular protein changes precede hippocampal pyramidal cell loss following global ischemia in the rat. PMID- 7771285 TI - Dietary antioxidants and breast cancer risk: effect modification by family history. PMID- 7771286 TI - Effect of MAK-4 and MAK-5 on endothelial cell and soyabean lipoxygenase-induced LDL oxidation. PMID- 7771287 TI - Prevention of oxidant stress by Student Rasayana (SR). PMID- 7771289 TI - In vitro ergothioneine administration failed to protect isolated ischaemic and reperfused rabbit heart. PMID- 7771288 TI - Biochemical changes induced by Maharishi Amrit Kalash (MAK-4) and MA-208 in diet induced hypercholesterolemic rabbits. PMID- 7771291 TI - Free radicals and the pathogenesis of neuronal death: cooperative role of excitatory amino acids. PMID- 7771290 TI - Pentoxifylline interferes with potential sources of free radical generation during endotoxemia. PMID- 7771292 TI - Free radicals and ocular disease. AB - Ames, Shigenaga, and Hagen recently published a thorough review of the relationship between oxidants, antioxidants, and degenerative diseases of ageing. They point out that only 9% of Americans daily consume the two fruits and three vegetables recommended by the National Cancer Institute and the National Research Council/National Academy of Science. In addition to antioxidants, these foodstuffs contain many essential micronutrients. To date, specific recommendations for antioxidant supplementation have not been made by any governmental agency or professional association. A number of clinical, basic, and epidemiological studies have implicated free radical induced lipid peroxidation in various ocular disorders. It would seem prudent that those persons at greatest risk for these disorders take some precautions, which could include sunglasses that filter ultraviolet light; hats that shield the eyes from direct sunlight; and the ingestion of fruits, vegetables, and antioxidants. PMID- 7771293 TI - Active oxygen mechanisms of UV inflammation. AB - Active oxygen radicals are important in the pathogenesis of UV irradiation injury. The initiating mechanisms involve the generation of hydroxyl radicals, superoxide, and organic hydroperoxides due to photochemical reactions. These active oxygen species lead to DNA strand breakage, mutation and the generation of inflammatory mediators such as cytokines and arachidonic acid metabolites which amplify the irradiation-induced inflammation. Several compounds have recently been utilized to successfully decrease these effects. Improved understanding of the mechanisms by which active oxygen species induce injury in skin now promises improved treatment. PMID- 7771295 TI - The development of the frontal lobe. A view from the rear of the brain. PMID- 7771294 TI - Oxygen-free radicals at myocardial level: effects of ischaemia and reperfusion. PMID- 7771296 TI - The clinical signs and symptoms of frontal lobe seizures. Phenomenology and classification. PMID- 7771297 TI - Frontal lobe epilepsy. Some clinical characteristics. PMID- 7771299 TI - Preoperative digital electroencephalography in frontal lobe epilepsy. PMID- 7771298 TI - Repetitive motor activity in frontal lobe epilepsy. PMID- 7771300 TI - High-resolution electroencephalographic studies of cognition. PMID- 7771301 TI - Magnetic resonance imaging in frontal lobe epilepsy. PMID- 7771302 TI - Role of human prefrontal cortex in attention control. AB - Without a functioning dorsolateral prefrontal cortex, humans are stimulus bound and have little confidence in their ability to interact with the environment. Deficits in inhibitory control of external and internal processes coupled with impaired temporal coding of stimuli and detection capacity for novel events leave the patient functioning in a noisy internal environment without critical spatiotemporal cues. Some of these proposals are similar to those of Nauta (104). Based on connectivity of the prefrontal cortex, Nauta suggested that this region was ideally suited to generate and evaluate internal models of action. It is proposed that, in addition to this generation function, the prefrontal cortex is crucial for detecting changes in the external environment and for discriminating internally and externally derived models of the world. This chapter has described a cascade of deficits that result from damage to the dorsolateral prefrontal cortex. Awareness of the sensory world, and of the apparent stream of internal and external events, is impaired by deficits in novelty detection. Changes in the world, internal or external, may not be noticed in a noisy internal milieu. These deficits contribute to impaired reality monitoring and to a subsequent lack of confidence in behavior. An inability to bridge temporal gaps and temporally sequence internal events, together with deficits in inhibitory control systems, contribute to an impairment in the ability to generate coherent representations of alternate or counterfactual realities. PMID- 7771303 TI - Presurgical evaluation in frontal lobe epilepsy. A multimethodological approach. PMID- 7771305 TI - Intracranial electroencephalographic investigation in frontal lobe epilepsy. PMID- 7771304 TI - Positron emission tomography in frontal lobe epilepsy. PMID- 7771306 TI - Human supplementary sensorimotor area. Electrical stimulation and movement related potential studies. PMID- 7771308 TI - Frontal lobe epilepsy. Compartmentalization, presurgical evaluation, and operative results. PMID- 7771307 TI - Video-stereo-electroencephalographic investigation of orbitofrontal cortex. Ictal electroclinical patterns. PMID- 7771309 TI - Surgery of frontal lobe epilepsy. PMID- 7771310 TI - Frontal degenerative dementia and neuroimaging. PMID- 7771312 TI - Aspects of human frontal lobe function. PMID- 7771313 TI - Lateralization in the frontal lobes. PMID- 7771311 TI - Anatomical and functional circuits in prefrontal cortex of nonhuman primates. Relevance to epilepsy. PMID- 7771314 TI - Memory and planning. Two temporal perspectives of frontal lobe function. PMID- 7771316 TI - Protein destabilization at low temperatures. PMID- 7771315 TI - A historical perspective. The rise and fall of prefrontal lobotomy. PMID- 7771317 TI - Stability of alpha-helices. PMID- 7771318 TI - Engineering the stability and function of gene V protein. PMID- 7771319 TI - Staphylococcal nuclease: a showcase of m-value effects. PMID- 7771321 TI - Free energy balance in protein folding. PMID- 7771320 TI - Studies on protein stability with T4 lysozyme. AB - A series of mutants of phage T4 lysozyme have been constructed and have permitted a systematic analysis of different aspects of protein stability and folding. One striking result has been the ability of the protein to accommodate changes at many sites, yet still fold and retain activity. This shows that many amino acids in the sequence of the protein are nonessential for protein folding and stability. Such amino acids appear, predominantly, to be those that are mobile and/or largely exposed to solvent. Even though buried residues seem to be more important, it is still possible to change these as well. In some cases individual amino acids have been replaced. In other cases it has been found that a combination of substitutions permits repacking of the core. Such repacking is associated with adjustments of both the main chain and side chains. Only rarely do side chains rotate into radically new orientations. Taken together, substitutions of core residues confirm the overall importance of the hydrophobic effect as the dominant factor in stabilizing the folded structures of proteins. "Cavity-creating" substitutions of the form Leu-->Ala show, as expected, that the burial of the bulky leucine side chain within the core of the protein confers greater hydrophobic stabilization than is the case for the smaller alanine side chain. Leu-->Ala substitutions that create large cavities are especially destabilizing because they result in a loss of both hydrophobic and van der Waals interactions. In cases where the protein relaxes to reduce the size of the putative cavity, alternative van der Waals interactions are generated and the overall destabilization of the protein may be less severe than in cases where a large cavity is formed. PMID- 7771322 TI - Structure and stability of membrane proteins. PMID- 7771323 TI - Modeling protein stability as heteropolymer collapse. PMID- 7771324 TI - Studies on denaturation of proteins. XIII. A theory of denaturation. 1931. PMID- 7771325 TI - Leukotrienes as Mediators of Asthma and Inflammation: Basic and Applied Research. Proceedings of an international workshop. Interlaken, Switzerland, September 7 12, 1992. PMID- 7771326 TI - Prostaglandin E2 regulation of the immune response. PMID- 7771327 TI - 5-Lipoxygenase inhibitors in the treatment of inflammatory bowel disease. PMID- 7771329 TI - The interaction among granulocyte lipid mediators and the generation of oxygen radicals in antigen-induced airway hyperresponsiveness. PMID- 7771328 TI - 5-Lipoxygenase activating protein and leukotriene C4 synthase: therapeutic targets for inhibiting the leukotriene cascade. PMID- 7771330 TI - Clinical and experimental studies of leukotrienes as mediators of airway obstruction in humans. PMID- 7771331 TI - Release of urinary leukotriene E4 in asthmatic subjects: a review. PMID- 7771332 TI - Aspirin-induced asthma: an update and novel findings. PMID- 7771333 TI - Summary: leukotrienes as mediators of asthma in humans but not always in experimental animals. PMID- 7771334 TI - Bronchial provocation with leukotrienes and other stimuli. PMID- 7771335 TI - Influence of leukotriene antagonists on baseline pulmonary function and asthmatic responses. PMID- 7771336 TI - Evidence for a specific role of leukotriene E4 in asthma and airway hyperresponsiveness. PMID- 7771337 TI - Mode of action of the leukotriene synthesis (FLAP) inhibitor BAY X1005. Implications for biological regulation of 5-lipoxygenase. PMID- 7771338 TI - Eosinophil eicosanoid relations in allergic inflammation of the airways. AB - Eosinophils are prominent features of allergic inflammation and can contribute to this process through release of inflammatory enzymes, granule-associated proteins, and leukotriene products. There is considerable interest in the fact that selected cytokines enhance eosinophil generation of leukotrienes. Therefore, future directions must include efforts to identify factors that regulate eosinophil synthesis of leukotrienes and therapeutic agents that might control these specific inflammatory responses. PMID- 7771339 TI - Role of cysteinyl leukotrienes in spontaneous asthmatic responses. PMID- 7771340 TI - Summary: the pharmacology of leukotrienes in asthma. PMID- 7771341 TI - The mediators of the early and late phases of allergic rhinitis. PMID- 7771342 TI - Leukotrienes as mediators of nasal inflammation. AB - The three sets of studies that we have described support the notion that leukotrienes play a role in the nasal inflammatory response to allergen challenge. Strong inhibition of both leukotrienes and symptoms by A-64077, a trend toward inhibition of both leukotrienes and symptoms by SC-45662, and a lack of effect on either leukotrienes or symptoms by dietary eicosapentaenoic acid provide a consistent association between alterations of leukotrienes and nasal symptoms. A great deal of evidence has now accumulated that leukotrienes are important mediators of inflammation in vivo, but we also know that the chronic stimulus of hay fever produces a much more complex picture than seen in an acute challenge model and that many other mediators such as kinins, other peptides, histamine, and eicosanoids produced outside the 5-lipoxygenase pathway are involved (34,35). Further clinical research will be needed to develop optimal dosing regimens and delivery systems to achieve high concentrations of potent and safe 5-lipoxygenase inhibitors at sites that are critical for producing clinically useful results by modulation of the 5-lipoxygenase pathway. PMID- 7771343 TI - Basic mechanisms in rheumatoid arthritis: the role of T lymphocytes in rheumatoid synovitis. AB - Undoubtedly, synovitis is a cell-mediated process involving various cell types, such as T cells, B cells, APC, monocytes/macrophages, synoviocytes, chondrocytes, and cytokines. Therefore, it is difficult to clarify the cell type that plays the central role in the inflammatory process. Despite this difficulty, there is strong evidence that T cells mediate the disease in collaboration with APC that bear specific antigenic peptides. The mediators released could perpetuate an ongoing inflammatory process in the joints irrespective of the nature of the initiating agents. Therefore, many approaches to a more specific immunotherapy for RA have been developed, directed toward the modulation of T cell function. Thus far, various forms of chemical and biologic treatment have been used, such as cyclosporin A and monoclonal antibodies directed against T-cell epitopes and IL-2 receptor, with some beneficial effects on the course of RA. The development of a more specific immunotherapy using reagents directed against the T-cell receptor and vaccination with specific T cells await further studies, since we still do not know the inciting antigen(s) in RA. Nevertheless, we are hopeful that the ongoing search for the still unknown antigen(s) will be successful, thus providing new and better treatment regimens for a still uncurable disease. PMID- 7771344 TI - Novel structural and functional properties of leukotriene A4 hydrolase. Implications for the development of enzyme inhibitors. AB - Recent work in our laboratory, some of which is described in this report, has established that LTA4 hydrolase is a bifunctional metalloenzyme that contains one zinc atom, essential for both catalytic activities. The well-characterized epoxide hydrolase activity, i.e., the conversion of LTA4 into LTB4 is inhibited by exposure to LTA4, and this irreversible enzyme inactivation also affects the peptidase activity. In contrast, the peptide hydrolysis proceeds without any signs of enzyme inactivation, can be stimulated by physiologic concentrations of chloride ions, and is critically dependent on the presence of a Glu residue in position 296 of the protein. A model of the active center, which summarizes these novel structural and functional properties of LTA4 hydrolase, is presented in Fig. 6. PMID- 7771346 TI - Regulation of leukotriene production by cytokines. PMID- 7771345 TI - Lipoxin recognition sites of human neutrophils. PMID- 7771347 TI - Inhibition of leukotriene production by inhibitors of lipoxygenation. PMID- 7771348 TI - Current approaches to estimation of eicosanoid formation in vivo. PMID- 7771349 TI - Leukotriene receptors and their selective antagonists. PMID- 7771350 TI - Summary: the enzymes, accessory proteins, and receptors of leukotriene metabolism and their inhibition and antagonism. PMID- 7771351 TI - Cytokine regulation of mouse mast-cell-specific protease genes. PMID- 7771352 TI - Transport and metabolism of leukotrienes. PMID- 7771353 TI - Microvascular mechanisms in inflammation. PMID- 7771354 TI - [The use of T650 in bony filling: experimental and clinical results]. PMID- 7771355 TI - [Relationship between endocrinology and craniofacial growth. I: Puberty and craniofacial growth. II: Growth of the craniofacial skeleton]. AB - In this literature, a review is given of the endocrinology and morphology of the craniofacial complex. This article reviews in a first part the endocrinology of puberty and general growth aspects. Afterwards the adolescence growth spurt of the face and the hormonal regulation will be focused. In a second part the morphogenetic aspects together with growth area's and growth theories of the craniofacial complex will be discussed. At last a detailed description of the maxillary and mandibular growth is given. PMID- 7771356 TI - It's not business as usual anymore! PMID- 7771357 TI - The primrose path. PMID- 7771359 TI - Comment on superimposition techniques. PMID- 7771360 TI - More comments on superimposition techniques. PMID- 7771358 TI - Cost, risk, regulation, fees. PMID- 7771361 TI - Condylar movement and mandibular rotation during jaw opening. AB - Inaccurate description of mandibular rotation can have profound effects on orthognathic surgical treatment planning and surgical outcome, as well as affect the precision of appliances fabricated on articulators. Disagreement exists concerning movements of the condyle during jaw opening. Although mandibular function is often described as rotation around an instantaneous center located outside of the condyle, many believe that jaw opening occurs around an axis of rotation that remains fixed at the center of the condylar head. In this study, condylar movements and centers of mandibular rotation during jaw opening were examined in normal subjects with the Dolphin Sonic Digitizing System. All of the subjects demonstrated both translation and rotation of the condyle during initiation of jaw opening, and none had a center of mandibular rotation located at the condylar head. The findings support the theory of a constantly moving, instantaneous center of jaw rotation during opening that is different in every person. There were also differences in movement within the subjects between experimental trials. The uncertainty of predicting mandibular rotation for a given patient should be considered when planning surgical treatment and fabricating orthodontic appliances. PMID- 7771362 TI - The effects of samarium-cobalt magnets and pulsed electromagnetic fields on tooth movement. AB - The purpose of this study was to determine whether the application of either samarium cobalt magnets or pulsed electromagnetic fields could increase the rate and amount of orthodontic tooth movement observed in guinea pigs. In addition, the objective was to evaluate the effect of a magnetic field on bony physiology and metabolism and to monitor for possible systemic side effects. Fifteen grams of laterally directed orthodontic force were applied to move the maxillary central incisors of a sample of 18 young male Hartley guinea pigs divided into three groups: group 1, an orthodontic coil spring was used to move the incisors; group 2, a pair of samarium-cobalt magnets provided the tooth moving force; and group 3, a coil spring was used in combination with a pulsed electromagnetic field. The results showed that both the static magnetic field produced by the samarium-cobalt magnets and the pulsed electromagnetic field used in combination with the coil spring were successful in increasing the rate of tooth movement over that produced by the coil springs alone. The mechanism producing this effect appears to have involved a reduction in the "lag" phase often seen in orthodontic tooth movement. Both magnetically stimulated groups also showed increases in both the organization and amount of new bone deposited in the area of tension between the orthodontically moved maxillary incisors. PMID- 7771363 TI - Cephalometric and computed tomographic predictors of obstructive sleep apnea severity. AB - The interaction between craniofacial structure assessed by lateral cephalometry, and tongue, soft palate, and upper airway size determined from computed tomography (CT) scans was examined in 25 control subjects and 80 patients with obstructive sleep apnea (OSA). On the basis of the cephalometric analyses, the patients with OSA had retruded mandibles with larger ANB angle differences, elongated maxillary and mandibular incisors and mandibular molars, and high total upper and lower face heights The computed tomographic evaluations revealed that patients with OSA also had larger tongue, soft palate, and upper airway volumes. Men with OSA and skeletal Class I malocclusions had significantly larger soft palates than comparable controls. Both tongue and soft palate volumes were positively correlated with body mass index. A principal component analysis reduced the database, and one significant correlation was identified. Subjects with high total, upper and lower face heights, elongated maxillary and mandibular teeth, and proclined lower incisors were observed to have large tongue, soft palate, and upper airway volumes, to have a higher apnea index and to be obese. Linear regression analysis indicated that a high apnea index was seen in association with large tongue and soft palate volumes, a retrognathic mandible, an anteroposterior discrepancy between the maxilla and mandible, an open bite tendency between the incisors, and obesity. PMID- 7771364 TI - Retention capacity of the bracket bases of new esthetic orthodontic brackets. AB - Tensile bond strength and bond failure locations were evaluated in vitro for three types of direct bonding cements (self-cured diacrylate, dual-cured diacrylate, and dual-cured glass ionomer) with four types of brackets (stainless steel, polycarbonate, ceramic, and ceramic-polycarbonate) by using a plastic cylinder as the substrate. A highly filled, self-cured diacrylate cement gave the highest bond strength values with the polycarbonate, stainless steel, and ceramic polycarbonate brackets. A dual-cured diacrylate cement gave the highest bond strength with a mechanically retained ceramic bracket. The dual-cured glass ionomer cement gave the highest bond strength values with a silanated ceramic bracket. All bond failures occurred at the bracket/cement interface with the stainless steel bracket, whereas failure locations were at the bracket/cement interface and within the cement with the polycarbonate bracket. Bond failures occurred between bracket and cement, within the cement, and within the bracket with the ceramic brackets. PMID- 7771365 TI - X-ray diffraction of nitinol orthodontic arch wires. AB - Superelastic mechanical behavior of nitinol alloy orthodontic wires is thought to be the result of a stress induced crystallographic transformation from austenite to martensite. The purpose of the study was to compare the SE mechanical behavior of nitinol wires to stress-induced phase changes. Eight nitinol arch wires having rectangular cross-sections were strained from 0% to 10% in tension with a mechanical testing machine. Load/extension plots were subjectively ranked for SE behavior. X-ray diffraction patterns were collected with and without 6% strain. Without strain, nitinol wires were found to be predominantly austenite with some wires containing a small amount of martensite. When strained 6%, superelastic wires demonstrated a phase transformation from austenite to martensite. XRD patterns were ranked for percent transformation and 110 peak width. Product rankings of the degree of superelasticity were positively correlated with the rank of martensitic transformation (p < 0.05). Superelasticity ranks were negatively correlated with XRD peak width ranks (p < 0.01). Increased peak width indicates greater cold work. A range of superelastic mechanical behavior and martensitic transformation is exhibited by wires currently on the market. Cold work and heat treatments are important variables to be controlled during the manufacture of nitinol products. PMID- 7771366 TI - Late lower arch crowding: the role of the transverse dimension. AB - Fifty subjects who were followed longitudinally between 13 and 18 years showed an average increase in lower arch crowding of 2.36 mm. This increase in crowding was examined in relation to tooth width, arch width and jaw width, actual and relative, and to changes in these dimensions with correlation and multiple regression analyses. No relationship was found between width dimensions and late crowding in the lower arch. PMID- 7771367 TI - Biomechanics of orthodontic correction of dental asymmetries. AB - Correction of dental asymmetries requires special attention in orthodontic treatment. Several types of asymmetries are described, along with the biomechanics needed for correction. Treatment with different appliance designs that correct these asymmetries with the lowest level of negative contribution from side effects will be compared with conventional treatment. PMID- 7771368 TI - The effect of mechanical deformation on the distribution of ions in fibroblasts. AB - The extracellular and intracellular sodium, potassium and chloride concentrations were determined in fibroblast cells located in the rat calvarium. The ionic values were determined by fluorescence microscopy after incubation with the fluorescent probes, sodium-binding benzofuran isophthalate (SBFI), potassium binding benzofuran isophthalate (PBFI) and 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ) (Dyes were supplied by CALBIOCHEM, Nottingham, England). After determination of the resting membrane potential, the calvaria were placed under tension by retraction of a micromanipulator. The fluorescence was measured again. A statistically significant difference was found in the calculated potassium ion concentration (Mann-Whitney; p < 0.05). This affected the resting cell membrane potential by an average of 5.2 mV. This effect was blocked by the addition of a potassium channel blocker, tetraethylammonium (TEA). PMID- 7771369 TI - A computer assisted photogrammetric analysis of soft tissue changes after orthodontic treatment. Part I: Methodology and reliability. AB - The purpose of this study was to use standardized facial photographs to compare the soft tissue profile changes in persons with Class II, Division 1 malocclusions who were treated with either an extraction or a nonextraction treatment modality. Ninety-one patients (44 extraction and 47 nonextraction) were evaluated with standardized facial photographs, available at pretreatment, posttreatment, and 2 years in retention. The photographs were digitized and displayed on a computer monitor. Thirty-eight landmarks (18 frontal and 20 lateral) were located. From these landmarks, 29 angular and linear dimensions (8 frontal and 21 lateral) were constructed. Descriptive and analytical statistics were used to compare the absolute dimensions, as well as the incremental changes, between the extraction and nonextraction groups. The present findings indicate that (1) Photographs allow for measurement of structures from a profile, as well as frontal orientations. (2) Measurement of profile changes from facial photographs appear to be fairly reliable but also have significant limitations. (3) Certain landmarks tended to be less reliable than others, e.g., subnasale and gnathion. In general, measurements from frontal photographs were more reliable than those obtained from lateral photographs and linear measurements were more reliable than angular measurements. (4) Changes in head posture within the cephalostat have an impact on vertical facial dimensions measured from frontal photographs. Horizontal dimensions were effected to a lesser degree. (5) Facial structures that lie closer to the camera appeared to be relatively larger than structures located farther from the camera. (6) The overall process of evaluating facial changes from photographs is both technique and operator sensitive. (7) More research specifically testing the photogrammetric method in a clinical setting is needed. PMID- 7771370 TI - The reproducibility and repeatability of the Wits analysis. AB - Since the introduction of the Wits analysis, the validity of the method has been questioned, as the functional occlusal plane in particular has been cited as a major source of error. This may be either subjectively placed or defined by existing cephalometric methods. A study is therefore reported of the repeatability (intraobserver comparison) and reproducibility (interobserver comparison) of the Wits assessment on the basis of a double series of tracings by each of two observers. No statistically significant difference was found for the repeatability of distance AO-BO by either observer, but interobserver repeatability was less satisfactory, and the mean values varied by approximately 75%. It was also found that the highest single error between two series of tracings was 3.1 mm (observer A) and 5.8 mm (observer B). PMID- 7771373 TI - Editorial: In which orthodontics discovers a defender. 1973. PMID- 7771372 TI - Adult versus adolescent Class II correction: a comparison. AB - The interest of the adult patient in orthodontics has increased as the demographics of the specialty of orthodontics has changed. There are major intreatment and posttreatment differences in Class II malocclusion correction between the adolescent and the adult. This article outlines the differences--and the similarities--between adolescent and adult Class II malocclusion correction. The differences and similarities are illustrated with case reports of a representative adolescent from the adolescent group and a representative adult from the adult group. PMID- 7771371 TI - Odontogenic adenomatoid tumors associated with orthodontic treatment. AB - Because of a predilection for occurrence in the anterior jaw in association with an unerupted tooth, the odontogenic adenomatoid tumor (OAT) will sometimes be discovered in the context of an orthodontic procedure to promote and guide eruption of the tooth. Two cases illustrate this situation. Some other lesions that might have a clinical presentation similar to the OAT are named. PMID- 7771374 TI - Medical examiners' attitudes toward organ procurement from child abuse/homicide victims. AB - Solid organ transplant provides lifesaving therapy for infants and children with otherwise terminal diseases, but it is severely limited by donor organ supply. Medical examiners perform a pivotal role in the organ procurement process by determining whether a "heartbeating cadaver" on life support is a medicolegally suitable donor. This descriptive questionnaire study assesses medical examiner practice and behavior regarding organ procurement from child abuse/homicide victims. Obtaining forensic evidence for judicial purposes and releasing organs to children awaiting transplantation are not necessarily conflicting values. Greater than 60% of medical examiners sampled would agree to release organs from abuse/homicide victims in the scenarios presented here if provided with requested information. Further confronting the origins of variable medical examiner practice in this area might result in the availability of additional solid organs for pediatric transplantation. PMID- 7771376 TI - An isolated perforation of the jejunum caused by child abuse. A case report. AB - Presented is the case of a 10-month-old boy who died of general peritonitis due to an isolated perforation of the proximal jejunum. The autopsy findings included multiple bruises and abrasions inflicted at different times, probable bite marks, an old cerebral contusion tear, malnutrition, and an involution of the thymus, this evidence cumulatively suggesting that the decedent was a battered child. The abdomen showed a general peritonitis, and the wall of the jejunum was ruptured on the antimesenteric surface, 2 cm from the duodenojejunal junction (the ligament of Treitz). Microscopically, the ruptured area showed a linear rent in the mucosa and muscularis, and the narrow necrotic lesion was surrounded by normal-appearing bowel tissue. Therefore, it appeared that an external force had compressed the jejunum against the spine, thus rupturing the jejunum near the duodenojejunal junction, a point of fixation. PMID- 7771375 TI - Traumatic pericallosal artery aneurysm. AB - We present the case of a 33-year-old man who sustained head trauma in a motor vehicle accident. He remained unconscious from the time of the accident until his death 10 days later. He was shown to have severe hemorrhage that destroyed the corpus callosum from genu to splenium in association with a pericallosal artery aneurysm (distal anterior cerebral artery aneurysm). In addition, hemorrhages typical of traumatic hemorrhages were found elsewhere in the brain. Clinically, he was considered to have suffered the rupture of a berry pericallosal artery aneurysm, which caused the motor vehicle accident. Review of the angiograms in relation to the forensic neuropathologic examination revealed features indicating that the aneurysm had a traumatic origin. We also discuss traumatic pericallosal artery aneurysms in the wider context of traumatic cerebral artery aneurysms. Features that aid in distinguishing traumatic from spontaneous berry aneurysm are considered. Only 17 cases of traumatic cerebral artery aneurysms have been reported in this site. To the best of our knowledge, this is the first such case to be reported in the forensic setting. PMID- 7771377 TI - Sudden death in elderly women with Fabry's disease. AB - We report two cases of elderly women who died unexpectedly. In both cases, light- and electron-microscopical examination proved a diagnosis of Fabry's disease. The major pathological changes were myocardial mottling, foamy vacuolation of myocytes and glomerular endothelial cells, and characteristic lamellar inclusions. Neither woman had either a personal or family history of Fabry's disease. Fabry's disease presenting as sudden death is very rare. We present the findings in two cases together with a review of literature particularly relevant to the cardiovascular system. PMID- 7771378 TI - Congenital diaphragmatic hernia. A case of sudden unexpected death in childhood. AB - A case is reported in which a congenital posterolateral diaphragmatic hernia of the Bochdalek type was the cause of sudden unexpected death in a 22-month-old girl. This case shows that not all late-presenting diaphragmatic hernias have a favorable prognosis. PMID- 7771379 TI - Sudden death in epilepsy due to an isolated subependymal giant cell astrocytoma of the septum pellucidum. AB - We report a case of sudden unexpected death in an individual with epilepsy. Autopsy revealed a subependymal giant cell astrocytoma of the septum pellucidum, but there were no other lesions of tuberous sclerosis. We discuss sudden death in epilepsy, deaths related to primary brain tumors, the pathology of subependymal giant cell astrocytoma, and whether or not such a tumor can exist outside the setting of tuberous sclerosis. We also discuss the implications such findings may have on surviving family members, as well as the important role of the forensic pathologist in such cases. PMID- 7771380 TI - Disseminated cryptococcosis and sudden death. Report of an autopsy case. AB - We report a case of sudden death due to terminal cryptococcal pneumonia in a patient not suspected to have AIDS. The correct diagnosis was found only by microscopic examination and serologic workup, illustrating the hazards faced by forensic pathologists and their assistants working without adequate information about the bodies under study. This case illustrates the need for the highest levels of caution and compliance with universal precautionary measures during autopsy procedures in the present days of the AIDS epidemic. PMID- 7771383 TI - Insertion of foreign bodies into the abdominal cavity. An unusual form of self mutilation. AB - Self-mutilation is self-infliction of bodily injury without a conscious suicidal intent. Repeated self-inflicted abdominal stab wounds with insertion of foreign bodies into the abdominal cavity is an uncommon form of self-mutilation. We describe such a case in a 35-year-old male inmate who committed suicide by hanging. At autopsy metallic foreign bodies were found in the liver and paraduodenal soft tissue. Because of its high prevalence in the incarcerated population, self-mutilation among prisoners should be given attention. Self mutilation should also be considered in cases of atypical behavior, psychiatric disorders, intoxication, mental retardation, and sudden death from unexplained causes. PMID- 7771381 TI - Death by fraternity hazing. AB - Fraternity hazing can cause a variety of injuries and deaths. We recently had the opportunity to investigate a heat-related death that occurred during a college fraternity event. The original death investigation did not consider the circumstances of death, environmental conditions, or the subtle autopsy findings related to heat stroke. This case is intended to alert health care professionals that deaths on college campuses may be related to fraternity hazing and may require in-depth investigations. An analysis of the death and a discussion of heat-related injuries are presented. PMID- 7771382 TI - Death caused by an allergic reaction to ethanol. AB - Death as a result of anaphylaxis remains rare and is only occasionally related to ingestion of common substances. This article reports a death due to an allergic reaction to ethanol, as well as a review of the reported deaths in the literature attributed to ethanol. This report emphasizes the importance of awareness of such obscure allergies by forensic pathologists, the significance of antemortem testing, and the value of gathering accurate medical information, both antemortem and postmortem. PMID- 7771384 TI - Pulmonary cartilage embolism: fact or artefact? AB - Microscopic examination of the lungs of a victim of traumatic asphyxia showed the presence of isolated foci of pulmonary bone marrow and cartilage embolism, although no macroscopic fractures were found. This condition could have resulted from a microfracture at a costochondral junction caused by the severe chest compression that led to the victim's death, or it might have been a resuscitation artefact. The possible role of pulmonary cartilage embolism as a marker of antemortem injury is considered. PMID- 7771385 TI - Splenic odyssey. Traumatic retropharyngeal displacement of thoracoabdominal viscera. AB - The retropharyngeal space (RPS) is a fascial compartment of the midline of neck, posterior to the pharynx, anterior to the spine. Pathologic involvement of RPS includes tumors, abscesses, and traumatic hematomas, all of which may dissect inferiorly into the thoracic compartment. We describe two cases in which severe trauma of the torso resulted in dissection of thoracoabdominal contents upward into the RPS--an apparently undocumented phenomenon. PMID- 7771386 TI - Suicidal ingestion of barium-sulfide-containing shaving powder. AB - Physicians, familiar with the common usage of barium medicinally as the contrast agent barium sulfate, may consider it an innocuous or at most a minimally harmful compound. The barium cation is extremely toxic and produces characteristic gastrointestinal symptoms, periorbital and extremity paresthesia, hypertension, and progressive flaccid muscular paralysis. Profound hypokalemia also may be induced. Overdose may be rapidly fatal unless the ingestion is recognized and appropriate treatment is instituted expediently. PMID- 7771387 TI - Fatal acute pancreatitis caused by valproic acid. AB - We describe a case of a 31-year-old woman with cerebral palsy who developed fatal acute hemorrhagic pancreatitis while being treated with valproic acid to control her seizure activity. Acute pancreatitis is usually due to alcohol ingestion or biliary tract disease, and unusual causes include trauma, metabolic diseases, or drugs. Valproic acid is considered a safe drug, although rare cases of severe toxicity such as hepatitis and acute pancreatitis, including two fatalities, have been reported. Our review of the literature revealed that most patients who developed acute pancreatitis had serum levels of the drug within the therapeutic range, and most of the cases occurred either secondary to a recent increase in the dose or to initiation of treatment. It also appeared that the fatalities occurred due to a delayed diagnosis of acute pancreatitis, either resulting from an unsuspected diagnosis or to the deteriorated mental status of the patients receiving the drug, which precluded their ability to elaborate symptomatology. We believe that early diagnosis and withdrawal of the drug are significant factors determining the course of valproic-acid-associated pancreatitis. PMID- 7771388 TI - Death caused by triazolam and ethanol intoxication. AB - Gas chromatography-mass spectrometry was used for the quantification of the hypnotic drug triazolam in human samples. In our case, death was attributed to triazolam and ethanol intoxication. The whole blood concentration of triazolam was 7.0 ng/ml and that of ethanol was 230 mg/dl. Based on the literature, this is the lowest triazolam concentration that has been associated with death. PMID- 7771389 TI - Death by bull-edger. An unusual homicide using a woodworking implement. AB - Impulsive killers often use whatever instrument is close at hand in the perpetration of their deed. We describe a homicidal death, first thought to be accidental, in a rural sawmill where the assailant manipulated a large board of wood into a machine known as a bull-edger (which cuts logs into rough boards) in such a fashion as to cause the death of his work partner. The physics of the events at the scene as well as the subsequent investigation are discussed. PMID- 7771390 TI - Sudden death in an infant due to histiocytoid cardiomyopathy. A light microscopic, ultrastructural, and immunohistochemical study. AB - Histiocytoid cardiomyopathy is a rare cardiac disorder of infancy and childhood that predominantly affects girls under the age of 2 years. The clinical picture is usually dominated by severe cardiac arrhythmias, and sudden death may occur. In such instances, sudden infant death syndrome (SIDS) is often considered. Grossly, the affected heart usually shows small, multifocal, subendocardial or myocardial yellow-tan nodular lesions or poorly defined plaques. Occasionally, the lesional tissue is not apparent. Histological findings include sharply demarcated groups and sheets of cells with abundant foamy or granular cytoplasm, justifying the use of the term "histiocytoid" cardiomyopathy. The abnormal cells appear to be transformed cardiac myocytes that possess some features of the conducting system fibers; therefore, Purkinje cells are now believed to be the origin of these distinctive lesions. We describe and discuss the light microscopic, immunocytochemical, and ultrastructural findings in a previously healthy 12-month-old boy who died suddenly. PMID- 7771391 TI - Fatal impalement injuries after falls at construction sites. AB - Three fatal accidents suffered by men at construction sites are reported. The victims fell from a considerable height onto metal construction rods and died from impalement injuries. The particular features of wound morphology are discussed. The influence of alcohol and medicines is also considered as a contributory cause of the falls. PMID- 7771392 TI - Judicial hanging. PMID- 7771393 TI - Crohn's disease of the esophagus. AB - A 26-yr-old woman presented with odynophagia, dysphagia, and intermittent bloody stools. Clinical, endoscopic, and microscopic evidence confirmed the diagnosis of severe Crohn's disease of the oropharynx, esophagus, proximal stomach, terminal ileum, and colon. PMID- 7771394 TI - Acute hepatitis A with coexistent hepatitis C virus infection presenting as a virus-associated hemophagocytic syndrome: a case report. AB - A 23-yr-old male with acute hepatitis A and coexistent hepatitis C became critically ill 3 wk after the onset of fever and jaundice with progressive anemia, thrombocytopenia, and hepatosplenomegaly. Bone marrow biopsy revealed hemophagocytosis. Despite aggressive supportive treatment with parenteral steroids, the patient died of disseminated intravascular coagulopathy with gastrointestinal bleeding. Necropsy of the liver showed histiocyte aggregation in the portal area with hemophagocytosis. PMID- 7771395 TI - A lethal course of chronic hepatitis C, glomerulonephritis, and pulmonary vasculitis unresponsive to interferon treatment. AB - Several extrahepatic syndromes have been associated with chronic hepatitis C virus infection. In our patient (a 57-yr-old woman without risk factors for hepatitis), chronic active hepatitis C was diagnosed serologically and histologically. Three months later, membranoproliferative glomerulonephritis with compromised renal function and peripheral edema, cryoglobulinemia, and a vasculitis of the finger tips developed. During interferon treatment for 3 months, neither the clinical condition nor serological parameters improved significantly. Progressive dyspnea was due to bilobar pulmonary infiltration. Despite antibiotic, virostatic, and corticosteroid therapy, the patient died from respiratory failure. Autopsy revealed diffuse pulmonary vasculitis. Thus, this is the first description of chronic hepatitis C virus infection, glomerulonephritis, and cryoglobulinemia complicated by immunologically mediated pulmonary vasculitis. Because interferon therapy may be ineffective, immunosuppressive therapy should be considered. PMID- 7771396 TI - Dramatic improvement of watermelon stomach with alpha-interferon. AB - Watermelon stomach is a rare disorder causing gastric blood loss and iron deficiency anemia. We report a case that occurred during the course of post hepatitis C cirrhosis, which condition was dramatically improved by alpha interferon treatment. PMID- 7771397 TI - Metoclopramide-induced sulfhemoglobinemia. AB - Metoclopramide, a drug with oxidant activity, has infrequently been reported to cause methemoglobinemia in infants. We present a unique case in which a patient on chronic metoclopramide therapy developed sulfhemoglobinemia that resolved with subsequent discontinuation of the drug. Mechanisms that may be important in the formation of sulfhemoglobin also are discussed. PMID- 7771398 TI - Giardiasis diagnosed by biopsy of the colon and terminal ileum: unusual sites for a common pathogen. AB - Giardiasis is a common intestinal infection which commonly presents with nonspecific symptoms. Suspected cases are usually diagnosed by stool examination or duodenal aspirates or biopsies. The purpose of this case report is to alert physicians to the fact that the organism may be present in colonic and ileal biopsies when clinical symptoms prompt a clinician to perform colonic biopsies rather than the usual tests of stools and duodenal aspirates or biopsies. PMID- 7771399 TI - Megacolon as a presenting finding of acute pancreatitis associated with chronic ulcerative colitis: unusual presentation of an unusual association. PMID- 7771400 TI - A case of triple early gastric cancer in the remnant stomach. AB - A 63-yr-old man, who had undergone distal gastrectomy and gastrojejunostomy (Billroth II method) 32 yr previously for duodenal ulcer, was admitted with suspected gastric remnant cancer. An upper gastrointestinal series and endoscopy revealed a protruding lesion at the stoma of the remnant stomach. Total gastrectomy with resection of the adjacent jejunum was performed. Histological examination demonstrated two well-differentiated adenocarcinomas (a mixed type I and IIc lesion with submucosal invasion and a type IIa lesion with intramucosal invasion) and a type IIc mucocellular carcinoma located in the mucosa. Gastritis cystica polyposa also was observed in the remnant stomach. The combination of three early gastric cancers and gastritis cystica polyposa suggests that the mucosa of the remnant stomach had a high malignant potential. The patient has survived without recurrence for 5 yr since the operation. PMID- 7771402 TI - Agenesis of the gallbladder found at laparoscopy for cholecystectomy: an unpleasant surprise. AB - Gallbladder agenesis is a rare condition that results from the failure of the cystic bud to develop in the 4th wk of intrauterine life. Agenesis is usually discovered at laparotomy for cholecystectomy since ultrasound examination of a patient with suggestive symptoms not visualizing the gallbladder is compatible with chronic cholecystitis (shrunken gallbladder). The surgeon must prove agenesis by thoroughly examining the most common sites for ectopic gallbladders and by performing intraoperative cholangiograms. For unexplained reasons, most of the patients become asymptomatic after the operation. We present a new case of adult agenesis of the gallbladder in a patient who was taken to laparoscopic cholecystectomy for presumptive cholelithiasis. PMID- 7771401 TI - Melanin-like pigmentation of the duodenum. AB - We report a case of brown-black pigmentation of the duodenum found in an elderly female during endoscopy for unrelated reasons. Melanin-like pigmentation of the duodenum is a rare endoscopic entity of uncertain etiology and significance. Various theories related to the etiology and pathogenesis, as well as histochemical and electron microscopic characteristics, are discussed. PMID- 7771403 TI - Can we reliably diagnose neoplastic cysts preoperatively? PMID- 7771404 TI - Another treatment option for biliary strictures from chronic pancreatitis. PMID- 7771406 TI - Treatment of acute pancreatic pseudocyst. PMID- 7771405 TI - The mechanisms of penicillamine, trientine, and zinc in the treatment of Wilson's disease. PMID- 7771407 TI - Hepatic insufficiency developing as a result of flutamide treatment. PMID- 7771408 TI - Endoscopic sphincterotomy without fluoroscopic control in pregnancy. PMID- 7771409 TI - Gynecomastia and sexual disorders after the administration of omeprazole. PMID- 7771410 TI - Hepatitis C virus infection and angioimmunoblastic lymphadenopathy. PMID- 7771411 TI - Overwhelming eosinophilic gastroenterocolitis associated with intestinal obstruction and carcinoma of the colon. PMID- 7771413 TI - Helicobacter pylori in pediatric nonulcer dyspepsia: pathogen or commensal? PMID- 7771412 TI - Sensory testing of the gastrointestinal tract: is there a better way? PMID- 7771414 TI - Radiation safety reviewed. PMID- 7771415 TI - Gastroduodenal motility and dysmotility: an update on techniques available for evaluation. PMID- 7771416 TI - Immunogenetic aspects of primary sclerosing cholangitis: implications for therapeutic strategies. AB - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibro-obliterative inflammation of the intra- and extrahepatic bile ducts; in 70% of cases, it is associated with inflammatory bowel disease. The disease usually runs a progressive course, ultimately leading to biliary cirrhosis, hepatic failure, and sometimes cholangiocarcinoma, with a median survival of 12 yr after diagnosis. As yet, the etiology of primary sclerosing cholangitis remains unknown, although several recent studies have implicated immunogenetic factors as important pathogenic mechanisms. Besides liver transplantation for patients with end-stage cirrhotic liver disease and endoscopic therapy for patients with dominant extrahepatic bile duct strictures, recent studies have also shown promising results of drug therapy with ursodeoxycholic acid in the treatment of PSC. The purpose of this article is to summarize our current knowledge of the immunogenetic factors in the pathogenesis of PSC and to present support for drug therapy with ursodeoxycholic acid in the treatment of PSC. The genetic and immunological factors in the pathogenesis of PSC are outlined first, followed by a rationale of drug therapy with ursodeoxycholic acid in the treatment of PSC. PMID- 7771417 TI - Evidence of gender differences in esophageal pain threshold. AB - OBJECTIVE: To compare esophageal sensation thresholds between healthy males and females. METHODS: We used esophageal balloon distention to compare sensory thresholds between nine male and 10 female volunteers with a latex balloon (length 3 cm) positioned 5 cm proximal to the lower esophageal sphincter. Subjects indicated feeling: 0 (no sensation), 1 (aware of balloon but no discomfort), 2 (pain or discomfort) during rapid (170 cc/s) or slow (0.7 cc/s) balloon inflation rates as the balloon was inflated with increasing volumes of 2 cc. Females were studied on two separate occasions, days 5-7 and days 20-22 of their menstrual cycles, with day 1 being the first day of menses. RESULTS: Females had a significantly lower pain threshold and a trend toward lower awareness level. No significant differences in sensory perception were found between the two phases of the female cycle. Poor correlation (r = 0.35 in rapid, r = 0.4 in slow inflation) was found between subject height and balloon volume at perception of pain. CONCLUSION: Healthy females demonstrate a lower threshold to esophageal pain induced by balloon distention than healthy males. This difference is not explained by hormonal changes during normal menstrual cycle or by body size. This observation may explain in part the observed preponderance of females with unexplained chest pain of possible esophageal origin. PMID- 7771419 TI - Esophageal aperistalsis and gastroesophageal reflux disorder: return of peristalsis after H2-blocker therapy. AB - OBJECTIVES: Distal esophageal aperistalsis has rarely been reported among patients with gastroesophageal reflux disorder. The purpose of this study, therefore, was to address the frequency with which disorders of peristalsis in general--and distal esophageal aperistalsis in particular--occur in adults with gastroesophageal reflux disorder. PATIENTS AND METHODS: We studied 314 patients who were referred to our gastrointestinal motility laboratory. On the basis of the endoscopic data, they were divided into three groups: group I, symptomatic patients without endoscopic esophagitis; group II, patients with mild endoscopic esophagitis; and group III, patients with erosive esophagitis. An age-matched group of patients with chest pain unrelated to reflux served as the control. RESULTS: Some form of peristaltic dysfunction was recorded in 56% of the patients with gastroesophageal reflux disorder, significantly more than in the control group (p < 0.01). A significant correlation existed between the esophageal motor dysfunction scores and the severity of reflux disease. Distal esophageal aperistalsis was present in 3.1% of the reflux groups. There was a correlation between severity of reflux disease and the prevalence of aperistalsis. Aperistalsis occurred in none of the patients in group I, in 3.6% of group II, and in 12.5% of group III (p < 0.0001). Seven of the patients with aperistalsis who has been treated with H2-blockers were reexamined 4 months later. Return of peristalsis was seen in three of them. CONCLUSION: Esophageal aperistalsis can be seen in a minority of patients with severe gastroesophageal reflux disorder and is probably a reversible condition. PMID- 7771418 TI - The role of Helicobacter pylori in children with recurrent abdominal pain. AB - OBJECTIVES: Our major goals in this study were to determine the prevalence of Helicobacter pylori among Israeli children with recurrent abdominal pain and to establish whether a link exists between eradication of Helicobacter pylori and the recovery from abdominal pain. The alternative target was to examine whether the serological test can replace endoscopy in children. METHODS: Upper gastrointestinal endoscopy was performed in 80 children with recurrent abdominal pain. During endoscopy, antral biopsies were taken and sent for histological and bacteriological examination. RESULTS: The prevalence of H. pylori, which was indicated by Gram stain and urease test, was 54%. The positive cases were treated with bismuth combined with amoxycillin and metronidazole. Two months after completion of the treatment, 34 patients were reexamined. Twenty-nine of them (85%) became symptom free, and five (15%) remained symptomatic. These five children were retreated, and they also became symptom free. Eight months after completion of treatment, all 34 patients were reexamined and found to be asymptomatic. CONCLUSIONS: We found a high prevalence of H. pylori (54%) among Israeli children with recurrent abdominal pain; we also found that symptoms were effectively and significantly reduced by the eradication of H. pylori. The endoscopic examination cannot be replaced by serological test. PMID- 7771420 TI - The effects of antireflux therapy on pulmonary function in patients with severe gastroesophageal reflux disease. Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group. AB - OBJECTIVES: Gastroesophageal reflux can induce bronchospasm, and antireflux therapy has been shown to improve pulmonary function in patients who have gastroesophageal reflux disease (GERD) associated with asthma. Our objective was to study the pulmonary effects of antireflux therapy in patients who had severe GERD without clinically apparent lung disease. METHODS: In a Department of Veterans Affairs Cooperative Study, patients who had complicated GERD without important lung disease were randomly assigned to receive one of three types of antireflux treatment, including two kinds of medical therapy and a surgical therapy. Patients had pulmonary function tests (PFTs), including total lung capacity, residual volume, forced vital capacity, forced expiratory volume in 1 s, maximal midexpiratory flow, and diffusing capacity for carbon monoxide. RESULTS: Two hundred forty-seven patients (243 men, four women; mean age 58 yr) entered the randomized trial, and 151 returned for PFTs at 1 yr. For the entire study group and for all three treatment groups, mean values for PFTs at 1 yr did not differ significantly from those at baseline. Even in subgroups of patients whose baseline PFTs were abnormal and whose esophagitis had healed completely, there were no significant changes in results of PFTs. CONCLUSIONS: For veteran patients with severe GERD and no obvious lung disease, 1 yr of antireflux therapy had no important effect on pulmonary function. These findings suggest that GERD is not commonly associated with inapparent, reversible pulmonary dysfunction. PMID- 7771421 TI - Transdermal nicotine and gastroesophageal reflux. AB - OBJECTIVES: Studies have shown that cigarette smoking acutely increases gastroesophageal reflux (GER). Patients prescribed transdermal nicotine often complain of pyrosis. The purpose of this study was to ascertain the effect of transdermal nicotine on GER. METHODS: Twenty volunteers (12 smokers and eight nonsmokers) were studied with a 24-h pH/motility apparatus while wearing a placebo patch for 24 h and a nicotine patch for a subsequent 24-h period. Each subject completed the entire 48-h monitoring session. RESULTS: A significant increase in the total acid score (p = 0.005), duration of acid exposure (p = 0.010), and supine duration of acid exposure (p = 0.004) were noted with transdermal nicotine versus placebo. There were no significant differences in esophageal motility after transdermal nicotine. CONCLUSIONS: Whether enhanced supine reflux is related to lower esophageal sphincter dysfunction, increased acid secretion, or defective acid clearance is not clear. Nonetheless, it may be prudent to recommend removal of the transdermal nicotine patch at night in the patient with symptomatic nocturnal GERD. PMID- 7771422 TI - Congenital markers for chronic intestinal pseudoobstruction. AB - OBJECTIVES: Chronic intestinal pseudoobstruction (CIP) is difficult to differentiate from true mechanical obstruction, so many patients undergo multiple operations before the diagnosis is established. This is because of a lack of easily identifiable signs and symptoms that can differentiate true intestinal obstruction from pseudoobstruction. The digital arch is the least common (10%) of the three patterns of fingerprints (arches, loops, and whorls) found in primates. Digital arches have also been reported in association with mitral valve prolapse, which in turn is associated with joint laxity. Fingerprints and mitral valve prolapse are congenital features and are influenced by heredity, so we evaluated CIP patients for coexistence of these clinical markers. METHODS: Fingerprints were examined in 1566 consecutive gastrointestinal specialty referrals. In 43 patients, the initial diagnosis of CIP was confirmed by subsequent testing. Because of the clinical impression that four features were present with increased frequency in CIP patients, these signs and symptoms were recorded prospectively: 1) number of digital arches (DA); 2) presence of mitral valve prolapse (MVP), 3) presence of joint laxity (JL), and 4) onset of constipation before age 10 (C < 10). RESULTS: Forty-three CIP patients (39 female, four male, ages 18-62) were seen. Using the test for significance of differences in proportions, the presence of DA, MVP, JL, and C < 10 proved significantly higher (p < 0.001) in CIP patients than in age- and sex-matched controls and the general population. CONCLUSIONS: We conclude that: 1) CIP may be a heritable syndrome because it is associated with heritable congenital markers (DA, MVP, JL, and C < 10; 2) these markers are identified with higher frequency in CIP patients than in the general population and in age- and sex-matched patients with other gastrointestinal disorders; 3) all four markers are easily detectable, and their recognition could lead to earlier diagnosis of the disorder. PMID- 7771423 TI - The cause of death in inflammatory bowel disease: a comparison of death certificates and hospital charts in Rochester, New York. AB - OBJECTIVE: This study examines the causes of death from Crohn's disease and ulcerative colitis by comparing death certificates with hospital charts as part of an ongoing, community-based analysis in Rochester, NY. METHODS: A registry of 1358 inflammatory bowel disease patients followed from January 1973 to December 1989 was analyzed for the cause of death by a study of death certificates as well as by a study of hospital records, including surgical pathology and autopsy records. A panel of physicians defined specific criteria for diagnosis, cause of death, and relation of death to inflammatory bowel disease. RESULTS: One hundred and thirty patients (59 with ulcerative colitis and 71 with Crohn's disease) from the registry were found to have death certificates recorded by Monroe County during this period. There was an 80% concordance of the death certificate to the hospital record for the cause of death and its relationship to inflammatory bowel disease. Discordance was noted in cases of colon cancer and surgical complications. CONCLUSIONS: Sixty-eight percent of Crohn's disease and 78% of ulcerative colitis patients died from causes unrelated to their inflammatory bowel disease. Deaths caused by Crohn's disease decreased from 44% in the 1973 1980 period to 6% in the 1981-1989 period. Crohn's disease was a direct cause of death in 25% of the female patients, whereas only 6% of male patients died directly of Crohn's disease. Colorectal cancer caused 14% of the deaths in ulcerative colitis patients, three times more often than in Crohn's disease patients. Excluding cancer, there were only two deaths directly due to ulcerative colitis, both in the first 2 yr after diagnosis. PMID- 7771424 TI - Limitations of continuous 24-h intragastric pH monitoring in the diagnosis of duodenogastric reflux. AB - OBJECTIVE: Long term gastric pH monitoring has been proposed to diagnose abnormal duodenogastric reflux. This study analyses the in situ reproducibility of continuous intragastric pH measurements to assess the influence of artifactual factors in producing spontaneous variations of pH values that might be frequently misinterpreted as episodes of duodenogastric reflux. METHODS: The investigation was carried out in 301 endoscopically proven duodenal ulcer patients (87 female, 214 male, mean age 46 yr). Each patient underwent 24-h gastric pH monitoring with two closely adjacent pH electrodes whose tips were about 2 mm apart. The two simultaneous pH tracings obtained from each patient were analyzed with regard to the number, characteristics, and discrepancies of unexpected alkalinization waves over the entire circadian cycle. RESULTS: The simultaneous pH tracings of the two channel datalogger we used ran almost superimposed for more than 23 h in 224 out of 301 (74%) duodenal ulcer patients. Major discrepancies between the two pH tracings of each recording were obtained in the remaining cases (77/301 = 26%). The most frequent event was represented by unexpected alkalinization waves that occurred mainly during nighttime and were recorded by only one of the two simultaneously measuring electrodes. As few as 16/244 (7%) patients showed synchronous, unexpected alkalinization waves that one might eventually consider to be duodenogastric refluxes. CONCLUSIONS: It is rather common that only one of two closely adjacent pH electrodes placed within the stomach measures longlasting pH elevations, particularly during the nocturnal period. This discrepancy is due to a poor in situ reproducibility of simultaneous pH recordings and indicates that pH readings might be influenced by interference and artifacts. Thus, the frequent differences between two simultaneous pH readings and the indirect measurement of the backflow of duodenal contents with long term gastric pH-metry do not allow us to rely on this technique to diagnose duodenogastric reflux. PMID- 7771425 TI - Scintigraphic evaluation of small bowel transit in healthy subjects: inter- and intrasubject variability. AB - OBJECTIVES: This study was performed to evaluate inter- and intrasubject variability of small bowel transit time and the effect of age and sex on transit in the small bowel. METHODS: Ten young subjects (five females) and nine elderly subjects (four females) were studied. Small bowel transit time was assessed by scintigraphic method using 99mtechnetium-sulfur colloid-labeled eggs. To evaluate intrasubject variability, 10 subjects underwent a second study on a later occasion. RESULTS: Mean small bowel transit time was 220.9 +/- 49 min with a range of 131 to 322 min, with no significant difference between the young and elderly groups or between sexes. There was a good intraobserver and interobserver reproducibility within the same test (r = 0.92 and r = 0.85, respectively). There was a significant biological variability between the first and the second studies, which was true whether the studies were processed independently (r = 0.43) or whether identical regions of interest were applied (r = 0.50). CONCLUSION: The normal range of small bowel transit time is wide in normal subjects; and there is a significant intrasubject biological variability for small bowel transit time. These findings should be kept in mind when using scintigraphic techniques for assessment of patients with motility disorders or when using the test repeatedly in the same subject in the evaluation of therapeutic measures. The results do not seem to be affected by age or sex. PMID- 7771426 TI - Low dose, short-term triple therapy for cure of Helicobacter pylori infection and healing of peptic ulcers. AB - OBJECTIVES: The aim of this study was to confirm the efficacy and tolerability of a new, low dose, short-term triple therapy for cure of Helicobacter pylori infection, as suggested by Bazzoli, in a larger population. METHODS: On an "intention-to-treat" basis, 116 patients with active (n = 41) or healed (n = 47) peptic ulcer disease or ulcer-like dyspepsia (n = 28) and H. pylori infection received a 1-wk course of omeprazole 20 mg b.i.d., clarythromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d.. Four weeks after treatment withdrawal, cure of H. pylori infection was evaluated by rapid urease test and histology. RESULTS: One hundred and sixteen patients returned for follow-up. In 108 patients, H. pylori could not be identified 4 wk after cessation of therapy. The eradication rate was calculated to 93%. In addition, all patients with active peptic ulcers showed complete healing at follow-up despite no further treatment. Drug acceptance and compliance was excellent. CONCLUSION: Triple therapy as suggested by Bazzoli with omeprazole (in this study given b.i.d. for better compliance), clarythromycin, and tinidazole is indeed highly effective for both cure of H. pylori infection and for healing of peptic ulcers, is easy to perform, is cheap, and is without clinically significant side effects, even in a larger population. PMID- 7771428 TI - The breakthrough phenomenon during alpha-interferon therapy of chronic hepatitis C: incidence, management, and outcome. AB - OBJECTIVES: Some patients treated with alpha-interferon (alpha-IFN) for chronic hepatitis C (CHC) initially respond with normalization of ALT only to encounter a rise in ALT while still on the drug. This phenomenon is called breakthrough (BT). We reviewed our experience with BT to clarify its incidence, pathogenesis, management, and outcome. METHODS: Charts from 71 consecutive patients with CHC treated with alpha-IFN were reviewed. Forty of these patients were part of a study of 1-yr escalating dose alpha-IFN, initiated at 2 million units (MU) 3 times per week. Endpoints that were evaluated were: reachievement of normal ALT, complete response (CR) (defined as normal ALT at the end of therapy), and sustained CR maintained for 6 months after therapy. RESULTS: Twenty-one (29.5%) patients sustained 28 BT events. Thirteen (46.4%) BT events occurred during the first 6 months of a course of alpha-IFN therapy, and 15 (53.6%) occurred during months 7 through 12. Of patients experiencing BT, six (28.6%) completed their course of therapy with a CR, of which two (9.5%) were sustained. By comparison, of 22 patients who normalized ALT without BT, all completed their course with a CR by definition (p < 0.0001), and nine (40.9%, p < 0.05) had a sustained CR. Of 28 BT events, 13 (46.4%) were followed by reattainment of normal ALT. Of 16 BT events managed with continuation of the same dose of alpha-IFN, normal ALT was reachieved in seven (43.8%). Of 12 BT events managed with an escalation in alpha IFN dose, six (50%) reachieved normal ALT. A full sequential series of hepatitis C virus RNA PCR from periods of elevated, normal, and again elevated ALT was available for 12 BT events. The pattern was +/+/+ in six, +/-/+ in five, and +/-/ in one. In one additional patient, an apparent BT was attributable to alpha-IFN induced autoimmune hepatitis. CONCLUSIONS: BT is a common event that may occur at any point during alpha-IFN therapy of CHC. This may limit the benefits of maintenance strategies. After a BT event, normal ALT can be reestablished in about 50% of cases, although the chance of a sustained CR falls to less than 10%. No advantage was demonstrated for escalating the alpha-IFN dose after a BT event. Therefore, we recommend continuation of the same dose as the initial approach. We suspect that BT relates to nonspecific ALT fluctuation in some patients and to emergence of resistant hepatitis C virus strains in others. Other causes of ALT elevation must also be considered in patients with apparent BT. PMID- 7771427 TI - Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathological entity. AB - OBJECTIVES: Colonic lymphoid nodules, also known as focal colonic lymphoid hyperplasia, have been previously described either as an indication of disease or as a normal variant in adults, with current opinion favoring the latter. The finding of isolated or confluent colonic lymphoid nodules on colonoscopy may nevertheless cause confusion with other endoscopic diagnoses. METHODS: In this study, we describe new endoscopic features of colonic lymphoid nodules, and we correlate them with other clinical and histopathological characteristics. Our experience is based on thorough evaluation of 13 cases of colonic lymphoid nodules that were consecutively observed during colonoscopy over the past 2 yr. RESULTS: Colonic lymphoid nodules may appear as red macules, as circumferential target lesions (halo sign), or as raised papules; they occur in both men and women, predominantly affect the rectum, and appear to be of no clinical significance. Histologically, colonic lymphoid nodules may involve the mucosa or the submucosa, in the form of either lymphoid aggregates or lymphatic nodules. CONCLUSIONS: With the widespread use of video colonoscopy, the macular or papular endoscopic characteristics of colonic lymphoid nodules should be increasingly recognized, confirmed histologically, and distinguished from other pathological lesions. Improved endoscopic recognition will allow the potential association of colonic lymphoid nodules with other colonic pathology to be eventually elucidated. PMID- 7771429 TI - Chronic hepatitis in patients with active hepatitis B virus and hepatitis C virus combined infections: a histological study. AB - OBJECTIVES: To evaluate whether peculiar histological changes are present in liver tissue of patients with chronic hepatitis by hepatitis B and hepatitis C (HBV and HCV) virus combined infections. METHODS: We studied liver biopsy specimens from 14 HB surface antigen/anti-HCV-positive patients consecutively admitted to hospital because of chronic liver disease from 1987 to 1992. Alcohol abusers, drug addicts, hepatitis delta virus- and HIV-infected subjects were excluded from the study. All of them were positive for serum HBV-DNA and/or intrahepatic HB core antigen and for serum HCV-RNA. Histological examination showed mild or moderate chronic hepatitis in nine cases and severe chronic hepatitis with cirrhosis in five cases. Two additional sets of liver biopsy specimens were also included in the study, consisting of liver samples from 14 patients with chronic liver disease due to active HBV infection alone (group B) and from 14 patients with active HCV infection alone (group C). Cases from group B and C matched for age, sex, and histological diagnosis with those from group B + C. Histological patterns of all the liver specimens of the three groups were re examined by two authors who scored the found features using a scale from 0 to 3. RESULTS: No peculiar histological pattern was revealed in group B + C, and most of the detected microscopic features were similarly present in all three groups. Bile duct lesions and well defined lymphoid follicles were found only in liver samples of patients from groups C and B + C. Ground-glass hepatocytes were observed only in cases from the groups B and B + C. CONCLUSIONS: Histological examination of liver tissue from patients with chronic HBV and HCV combined infection does not show either typical patterns or evidence that this subgroup of chronic viral hepatitis is a more severe form of liver disease than that caused by a single virus infection. The observation in liver samples of peculiar lesions by HBV or HCV infection does not exclude a combined infection by both viruses. PMID- 7771430 TI - The platelet count as a predictor of variceal hemorrhage in primary biliary cirrhosis. AB - BACKGROUND: Variceal bleeding is a common, life-threatening complication of primary biliary cirrhosis (PBC) that remains difficult to predict. OBJECTIVE: The aim of this study was to identify whether certain biochemical and hematological parameters may be used as predictors of variceal bleeding in patients with PBC. METHODS: Cox proportional hazard regression analysis was used to test whether various prognostic factors were significantly associated with the time of first bleeding in 63 patients with proven PBC, of whom 11 had subsequent bleeding. RESULTS: Both the first available platelet count and the bilirubin level were of significant value in predicting variceal bleeding, but only the platelet count was an independent predictor of bleeding. In the group of patients who subsequently bled, there was a progressive drop in the platelet count over the follow-up period, with a proportional increase in the risk of bleeding; a platelet count below 200 x 10(9)/L was strongly associated with variceal bleeding (p < 0.001). None of the patients with platelet count above 200 x 10(9)/L bled over a total of 136 patient-years follow-up. In the group who did not bleed, no change in platelet count was identified during follow up. CONCLUSION: We conclude that the platelet count can be used as a predictor of variceal bleeding in PBC. PMID- 7771431 TI - Evidence for an immunological pathogenesis of thrombocytopenia in chronic liver disease. AB - OBJECTIVES: To elucidate the role of platelet-associated IgG (PA-IgG) in the mechanism of thrombocytopenia associated with chronic liver disease. METHODS: Platelet count in blood, PA-IgG, and scintigraphic spleen/liver ratio as a marker of splenomegaly was examined in 214 individuals, including 16 controls showing nonspecific reactive change in liver biopsy and 198 patients with chronic liver disease. RESULTS: The mean blood platelet count decreased significantly according to severity of liver disease, from control to liver cirrhosis. PA-IgG levels increased significantly in relation to severity of liver disease, as did spleen/liver ratio. In chronic hepatitis or liver cirrhosis, an inverse correlation was found between platelet counts and PA-IgG levels. An inverse correlation was also observed between platelet count and spleen/liver ratio in liver cirrhosis. The splenic embolization resulted in a significant rise in platelet count and a significant fall in PA-IgG in the 14 cirrhotic patients. CONCLUSIONS: These results may give support to evidence for an immunological mechanism mediated by PA-IgG for the thrombocytopenia occurring in chronic liver disease. In the case of liver cirrhosis, this mechanism would act in addition to platelet pooling in the spleen on thrombocytopenia. PA-IgG may also have an important role in thrombocytopenia associated with chronic hepatitis, in which splenic platelet pooling is less marked. PMID- 7771432 TI - Clinical correlates of gallstone composition: distinguishing pigment from cholesterol stones. AB - OBJECTIVES: The prevalence of cholelithiasis has been established in population based surveys employing ultrasonography, and major risk factors have been identified. However, the clinical and epidemiological features that distinguish patients with pigment gallstones from those with cholesterol stones have received little attention. METHODS: We prospectively surveyed 551 patients undergoing cholecystectomy for gallstones at two teaching hospitals. Clinical and epidemiological data were collected during patient interviews and by chart review. Gallstones were collected at surgery; physical measurements were recorded, and stone composition was determined by visual inspection and infrared spectroscopy. RESULTS: Patients with pigment stones were older than patients with cholesterol stones (p < 0.00001). Almost all patients under age 40 yr old had cholesterol stones, but most patients over 70 had pigment stones. Cirrhosis was strongly associated with pigment gallstones (p < 0.00001), although alcohol consumption was unrelated. Univariate analyses suggested associations of stone composition with male sex, diabetes mellitus, educational attainment, and use of thiazides or oral contraceptives, but these were not significant in a logistic regression that adjusted for age, cirrhosis, and other variables. Patients with pigment cholelithiasis had stones that were generally smaller in diameter and fewer in number than those with cholesterol stones. CONCLUSIONS: Compared to patients with cholesterol gallstones, those with pigment stones are older and more likely to have a diagnosis of cirrhosis. In addition, their stones are smaller in size and fewer in number than those from patients with cholesterol cholelithiasis. PMID- 7771433 TI - Effect of erythromycin on gallbladder emptying in patients with antrectomy or truncal vagotomy. AB - OBJECTIVES: Erythromycin, a motilin-like agent, stimulates gallbladder contraction in healthy control subjects. Because the action of erythromycin is cholinergic dependent and possibly related to premature phase III migrating motor complex activity in the antrum, we investigated the effect of erythromycin on gallbladder volume in six patients with truncal vagotomy without gastric resection and 14 patients with antrectomy (6 with Billroth I anastomosis, 8 with Billroth II anastomosis), and we compared the results obtained with those in eight healthy controls. In addition, the effect of meal ingestion on gallbladder volume was studied. METHODS: Gallbladder volumes, measured with ultrasonography, were determined every 15 min for 180 min after erythromycin infusion (3 mg/kg i.v.), as well as 30 and 60 min after meal ingestion. RESULTS: Basal gallbladder volumes were not significantly different among the four groups. Erythromycin induced a significant (p < 0.01-0.05) gallbladder contraction of maximal 46 +/- 6% in the controls, 49 +/- 9% in the patients with truncal vagotomy, and 38 +/- 7% in the patients with antrectomy and Billroth I anastomosis. In the patients with antrectomy and Billroth II anastomosis, no significant reduction in gallbladder volume after erythromycin was observed. Meal-induced gallbladder contraction was normal in all patients, including those with Billroth II anastomosis. CONCLUSIONS: These results indicate that neither the long vagus nerve nor the antrum is essential for erythromycin-induced effects on the gallbladder. Because no significant reduction in gallbladder volume in response to erythromycin was observed in the patients with antrectomy and Billroth II anastomosis, we suggest that duodenojejunal anatomical integrity is essential for erythromycin-induced gallbladder contraction. PMID- 7771435 TI - The relationship between insurance class and severity of presentation of inflammatory bowel disease in children. AB - OBJECTIVE: To determine whether there is an association between insurance class and the severity of presentation of inflammatory bowel disease in children. METHODS: Twenty underinsured (either no insurance or Medicaid) children were computer-matched with 20 children with private insurance with regard to diagnosis and age but without regard to severity of disease from a pool of 63 patients (20 underinsured patients and 43 insured patients). We compared four patient-reported parameters and eight laboratory values. RESULTS: There were 22 patients with Crohn's disease (11 underinsured and 11 insured) and 18 patients with ulcerative colitis (nine underinsured and nine insured), with a mean age at diagnosis of 13.7 +/- 4.2 yr in the underinsured and 13.4 +/- 3.8 yr in the privately insured patients. Patients in the underinsured category had more than 2.5 times the weight loss of the privately insured patients (20.0 +/- 13.9 vs. 7.8 +/- 8.6, p < 0.005) and longer delay in months (10.3 +/- 10.9 vs. 2.7 +/- 2.6, p < 0.005) before the diagnosis was made. Laboratory data in the underinsured children indicated that they were more ill at time of presentation than the insured patients. The underinsured patients had significantly lower hemoglobins (10.5 +/- 2.4 vs. 12.5 +/- 2.1, p < 0.01), a higher erythrocyte sedimentation rate (59 +/- 35 vs. 21 +/- 24, p < 0.005), and higher platelet counts (536 +/- 205 x 10(3) vs. 418 +/- 140 x 10(3), p < 0.05) compared to the insured group. Alkaline phosphatase levels, normally elevated in children during osseous growth, were significantly depressed in the underinsured group when compared with the insured group (117 +/- 42 vs. 155 +/- 71, p = 0.05). CONCLUSION: Underinsured children have clinical and laboratory parameters that indicate that their disease is more severe at presentation than privately insured patients. We postulate that this is partly related to the fact that underinsured patients have inferior access to quality healthcare when compared to privately insured patients. PMID- 7771434 TI - Acquired gallstone opacification during cholelitholytic treatment with chenodeoxyholic, ursodeoxycholic, and tauroursodeoxycholic acids. AB - OBJECTIVES: The appearance of gallstone opacification during oral bile acid administration indicates that stones are no longer susceptible to dissolution and represents, therefore, a definitive treatment failure. Ursodeoxycholic acid (UDCA) has been imputed to facilitate gallstone opacification; however, data regarding the comparative occurrence of gallstone opacification during UDCA and chenodeoxycholic acid (CDCA) administration are not yet available. Our objectives were to evaluate the frequency of acquired opacification in gallstone patients taking UDCA and in gallstone patients taking CDCA, to verify whether or not gallstone opacification is a peculiar side effect of UDCA treatment and, further, to evaluate gallstone opacification in gallstone patients receiving tauro-UDCA (TUDCA) to verify whether the administration of the more soluble tauroconjugate might prevent the deposition of calcium salts on the stone surface. METHODS: 106 gallstone patients on UDCA, 125 gallstone patients on CDCA, and 31 gallstone patients on TUDCA were evaluated. Before treatment, all patients had radiolucent gallstones as assessed by oral cholecystography; further cholecystographic evaluations were performed every 6 months during treatment. RESULTS: The frequency of gallstone opacification was 13.2% (14/106) in UDCA patients, 8.8% (11/125) in the CDCA patients, and 12.9% (4/31) in the TUDCA patients. The differences were not statistically significant (p = NS). Sex, stone size, dose of bile acid, and duration of treatment were not significantly related to an increased frequency of gallstone calcification in any of the treatment groups. The frequency of gallstone opacification appeared to be higher in older patients. CONCLUSIONS: 1) UDCA rich bile is not a major predisposing factor for acquired gallstone opacification; 2) the administration of TUDCA does not prevent gallstone opacification; 3) opacification could be related to the natural history of gallstone disease. PMID- 7771436 TI - Small colorectal polyps: histopathology and clinical significance. AB - OBJECTIVES: The development of colorectal adenomas and carcinoma involves both environmental and genetic factors. Wide variations among populations have been observed in the prevalence of adenoma. Investigations of the small colorectal polyps have been divergent. The distribution of these small polyps remains in controversy. The histology, clinical significance, and optimal treatment of such lesions have yet to be defined. The aim of the present prospective study is to ascertain the importance of small colorectal polyps in the Taiwanese and to define their histopathological nature, spatial distribution, and clinical significance. METHODS: We prospectively evaluated all patients referred for colonoscopy for miscellaneous indications. All raised lesions encountered during the procedure were removed or biopsied. Each polyp was estimated in situ by visual comparison with the known width of a standard fully opened biopsy forceps. Small colorectal polyps were defined as those measuring 8 mm or less in diameter. Histopathology of these small polyps were reviewed and correlated clinically. RESULTS: 124 patients were found to have 159 small colorectal polyps. There were 88 men (71%) and 36 women (29%). The mean ages were 60.2 yr for men and 50.8 yr for women. Solitary polyps were present in 68.5% of patients while 26.6% had two polyps and 4.9% had between 3 and 10 polyps; 60.4% of the small polyps were neoplastic, while 39.6% including 23.9% hyperplastic polyps were nonneoplastic; 50.3% of the small polyps were located in the rectosigmoid. Tubular adenomas accounted for 90.6% of the small neoplastic polyps. The neoplastic polyps predominated in each colorectal segment. The proportion of small neoplastic polyps was higher in older patients; 2.8% of the small adenomas showed moderate dysplasia. Severe dysplasia was noted in only one polyp. No malignancy was observed. The chi-square test with Yates' correction was used for statistical analysis. CONCLUSIONS: These findings reveal that a large share of the small colorectal polyps are neoplastic and therefore at risk to progress to carcinoma. The location of small polyps distributed at the rectosigmoid or the proximal colon was of no significance (p > 0.2) for the proportion of neoplastic polyps. The older patients probably have higher risk because of their higher proportions of small neoplastic polyps. All polyps should be removed when encountered during colonoscopy due to the high prevalence of adenomas among small colorectal polyps. PMID- 7771437 TI - Presentation and treatment of annular pancreas in an adult population. AB - OBJECTIVE: To describe a series of adult patients with annular pancreas, their presentation, and treatment modalities. METHOD: A retrospective chart review of patients seen at a multispecialty referral center from 1977 to 1994. RESULTS: Seven adult patients (ages ranging from 33 to 77 yr, four females and three males) presented with various symptoms and signs: abdominal pain (six patients) gastric outlet obstruction (two), pancreatitis (two), pancreatic mass (two), gastric/duodenal ulcer (one), and/or postoperative obstructive jaundice (one). The duration of symptoms ranged from 1 wk to 16 yr before diagnosis (median 18 months). Upper GI radiography was consistent with annular pancreas in two cases, CT scan in two cases (neither of which actually depicted the annulus), and four of six successful endoscopic retrograde cholangiopancreatographies. Three patients were diagnosed during operative procedures. Five of the seven patients required therapeutic operative procedures that included transduodenal sphincteroplasty, duodenojejunostomy, gastrojejunostomy, subtotal gastrectomy, or Whipple procedure. Four of the five had significant symptomatic relief. In one case, endoscopic sphincterotomy and biliary stent placement was therapeutic. CONCLUSIONS: 1) Annular pancreas occasionally presents in the adult population. 2) Although gastric outlet obstruction was seen in two of seven patients, a plethora of additional presentations included pancreatic mass, pancreatitis, peptic ulcer disease, and post-operative obstructive jaundice. 3) Diagnosis of annular pancreas was most commonly suggested by upper GI series or endoscopic retrograde cholangiopancreatography. However, fully 40% of diagnoses required surgery for confirmation. 4) In contrast to the pediatric population in whom gastrojejunostomy or duodenojejunostomy is the treatment of choice, a variety of surgical as well as interventional endoscopic procedures were utilized for effective treatment in adults with annular pancreas. PMID- 7771439 TI - Reliability of reported sunburn history in a case-control study of cutaneous malignant melanoma. AB - Reliability of reported sunburn history was assessed. Fifty cases and 50 controls were randomly selected from a population-based case-control study of skin examination practices and lethal melanoma in Connecticut. Eighty-two percent of these participants were interviewed from January 15, 1987, to May 15, 1989, and reinterviewed in 1990. The kappa coefficients ranged between 0.37 and 0.57; the intraclass correlation coefficients were similar and ranged between 0.34 and 0.69. There were no significant differences found by case-control status or sex for any variables, and the degree of disagreement was similar for cases and controls and could be considered free of recall bias. PMID- 7771438 TI - Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States. AB - The authors conducted a population-based case-control study of lung cancer in nonsmoking women in five metropolitan areas of the United States between December 1, 1985, and November 30, 1990. In-person interviews were conducted with 412 lung cancer cases and 1,253 population controls, yielding information on history of nonmalignant lung diseases that were diagnosed by a physician. When lung cancer cases were compared with controls, history of any previous lung disease was associated with a significant increased risk of lung cancer (adjusted odds ratio (AOR) = 1.56, 95% confidence interval (CI) 1.2-2.0). Several lung diseases, including asthma, chronic bronchitis, pneumonia, and tuberculosis, were reported more often by lung cancer cases than by controls, and the difference was statistically significant for asthma (AOR = 1.67, 95% CI 1.1-2.5) and chronic bronchitis (AOR = 1.60, 95% CI 1.1-2.4). Since significant increased risks were observed for asthma and tuberculosis diagnosed before age 21 years, it is unlikely that reported prior lung diseases were prediagnostic manifestations of lung cancers. The increased risks associated with previous lung disease were observed for adenocarcinomas and other carcinomas of the lung; the point estimates were generally higher for the latter category. The risks associated with previous lung diseases remained unchanged after adjustment for potential confounders, including environmental tobacco smoke exposure during childhood and adult life and dietary factors. PMID- 7771440 TI - Tobacco, alcohol, and colorectal tumors: a multistep process. AB - A case-control study in the Cote d'Or area of France used the multistep concept of colorectal carcinogenesis to compare lifetime tobacco consumption and present alcohol consumption in patients with small adenomas (less than 1 cm, n = 154) or large adenomas (n = 208) and in polyp-free controls (n = 427). Cancer patients (n = 171) were compared with population controls (n = 309). In men, smoking was associated with the risk of adenomas (odds ratio = 3.6 over 20 pack-years vs. nonsmokers, p < 0.001). Alcohol was a risk factor for large adenomas only, with relative risks of 4.2 (p < 0.01), 3.0 (p < 0.05), and 4.4 (p < 0.01) for consumptions of 20-39, 40-59, and 60 g/day compared with less than 10 g/day. When patients with large adenomas were compared with polyp-free controls, both alcohol and tobacco were independently related to the risk of tumor. There was no association between tobacco or alcohol intakes and cancer risk. In women, consumption was much lower in all groups, and no significant association with either risk factor was observed. These data suggest for the first time that there is an independent effect of alcohol and tobacco in men at different early steps of the adenoma-carcinoma sequence. They demonstrate the usefulness of such a model for etiologic studies on cancer. PMID- 7771441 TI - Blood lead levels in relation to menopause, smoking, and pregnancy history. AB - Postmenopausal bone loss may result in the release of lead stored in bone. This study examined Mexican-American women aged 20 years and older who participated in the Hispanic Health and Nutrition Examination Survey (1982-1984) to assess the influence of menopause, pregnancy history, and smoking on blood lead levels. After adjustment for factors likely to influence blood lead levels and for design effects, the authors confirmed associations with age, income level, education, degree of urbanization, and body mass. Blood lead concentrations were markedly higher among current smokers and postmenopausal women, with these two factors showing separate, roughly additive effects. Gravidity had little impact on blood lead level among premenopausal women. However, among postmenopausal women, never pregnant women had higher blood lead levels than did those who had ever been pregnant. The largest increase (4.4 micrograms/dl, 95 percent confidence interval 0.95, 7.8) was observed among smokers. In a separate analysis of postmenopausal women, women with recent menopause (4 years or less) had blood lead concentrations 1.4 micrograms/dl higher (95 percent confidence interval 0.20, 2.7) than did those whose menopause occurred more than 4 years previously. This finding, along with an overall slow decline in blood lead levels with each year after menopause, suggests that lead is being mobilized at rates consistent with the patterns of bone loss, placing women with recent menopause at increased risk for higher blood lead levels. PMID- 7771443 TI - Educational level and obstructive lung disease given smoking habits and occupational airborne exposure: a Norwegian community study. AB - The relation of educational level to obstructive lung disease, spirometric airflow limitation, and respiratory symptoms was examined in a two-phase cross sectional study of a Norwegian general population aged 18-73 years in 1985-1988. The first phase was a questionnaire survey. In the second phase, a stratified sample of those who responded in the first phase was invited to a clinical and respiratory physiologic examination. Altogether, 714 subjects attended, representing 84% of those invited. The prevalences of obstructive lung disease and spirometric airflow limitation were 7.8% and 4.5%, respectively. A total of 18% of the population had completed college, a further 60% had completed secondary school, and 21% had obtained a primary school education alone. The prevalence of both smoking and occupational airborne exposure decreased with increasing educational level. The sex-, age-, smoking-, and occupational exposure adjusted odds ratio of obstructive lung disease in primary-versus university educated subjects was 2.9 (95% confidence interval (CI) 1.3-6.5); in secondary- versus university-educated subjects it was 1.4 (95% CI 0.7-2.8). The corresponding values for spirometric airflow limitations were 5.2 (95% CI 2.0 13.4) and 1.8 (95% CI 1.2-2.7). All of the respiratory symptoms except breathlessness grade 2 were significantly associated with educational level after allowing for sex, age, smoking, and occupational airborne exposure. The survey indicates that educational level is a risk factor for airway disorders independent of smoking and occupational airborne exposure. PMID- 7771442 TI - Solvent exposure as a risk factor for Alzheimer's disease: a case-control study. AB - This case-control study investigates whether history of organic solvent exposure is associated with increased risk of Alzheimer's disease. The study base includes about 23,000 persons aged 60 years or more from the local membership of a health maintenance organization in Seattle, Washington, who entered the study between 1987 and 1992. Probable Alzheimer's disease cases (n = 193) who had presented with new dementia symptoms were identified, enrolled, and diagnosed by our Alzheimer's Disease Patient Registry following standardized criteria. Control subjects (n = 243), free of dementia and neurologic disease causing dementia, were selected randomly from the study base and frequency matched to cases for age and sex. Proxy informants provided specific solvent exposure history as well as job descriptions likely to involve solvent use as part of a comprehensive risk factor interview. Kappa statistics indicated substantial agreement for control control proxy solvent responses. History of exposure to one or more solvent groups (benzene and toluene; phenols and alcohols; ketones; other solvents) yielded an adjusted Alzheimer's disease odds ratio of 2.3 (95 percent confidence interval 1.1-4.7); among males only, it increased to 6.0 (95% confidence interval 2.1-17.2). Thus, past exposure to organic solvents may be associated with onset of Alzheimer's disease. PMID- 7771444 TI - Reproducibility of responses to telephone interviews: demographic predictors of discordance in risk factor status. AB - The reproducibility of responses to the Behavioral Risk Factor Surveillance System questionnaire was examined across the demographic strata used by the Centers for Disease Control and Prevention and state health departments for reporting prevalence estimates (specifically age, sex, income, employment, and marital status), as well as race/ethnicity, which has been previously examined. The authors administered the questionnaire twice, 21-94 days apart, to randomly selected residents of Massachusetts (response rates: first administration, 68% of eligible households; second administration, 68% of persons who completed the first interview). Initial interviews were conducted in March and October 1992. Among 448 respondents to both interviews, group mean distributions of seven demographic characteristics and 19 risk factors were highly consistent across the two interviews. Discordance in individual risk factor status ranged from 1.2% to 21.8% (median, 7.8%) and was symmetric in direction, i.e., as many respondents were considered at increased risk on the basis of the first interview and at low risk on the basis of the second interview as the reverse. Kappas ranged from 0.30 to 0.90 (median, 0.75). Education, household income, and interval between administrations were not associated with prevalence of discordance for any risk factor. Sex, age, race/ethnicity, marital status, and employment status were each predictive of variation in discordance for one or more risk factors, but no consistent effect of any individual demographic characteristic across risk factors was observed. The questionnaire has relatively uniform and generally good reproducibility across all demographic strata used for monitoring the Health Objectives for Year 2000 and other chronic disease surveillance activities. PMID- 7771445 TI - Re: "Vegetables, fruit, and colon cancer in the Iowa Women's Health Study". PMID- 7771446 TI - Re: "Male and female factors in fertility". PMID- 7771447 TI - Re: "Prevalence of low birth weight among Hispanic infants with United States born and foreign-born mothers: the effect of urban poverty". PMID- 7771448 TI - A short method for constructing an abridged life table. 1939. PMID- 7771449 TI - Confounding and effect-modification. 1974. AB - Confounding and effect-modification--both very central to epidemiologic thinking and research on causality--are closely related but distinctly separate concepts and phenomena. Both of them involve considerable subleties, with implications for problem conceptualization, study design, data analysis and inference. Some of these subtleties and their implications may warrant greater appreciation in the practice of epidemiologic research, while others require further conceptual development. PMID- 7771450 TI - Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. AB - Obesity, android fat distribution, and other anthropometric measures have been associated with coronary heart disease in long-term prospective studies. However, fluctuations in weight due to age-related hormonal changes and changes in lifestyle practices may bias relative risk estimates over a long follow-up period. The authors prospectively studied the association between body mass index (BMI) (kg/m2), waist-to-hip ratio, and height as independent predictors of incident coronary heart disease in a 3-year prospective study among 29,122 US men aged 40-75 years in 1986. The authors documented 420 incident coronary events during the follow-up period. Body mass index, waist-to-hip ratio, short stature, and weight gain since age 21 were associated with an increased risk of coronary heart disease. Among men younger than 65, after adjusting for other coronary risk factors, the relative risk was 1.72 (95% confidence interval (CI) 1.10-2.69) for men with BMI of 25-28.9, 2.61 (95% CI 1.54-4.42) for BMI of 29.0-32.9, and 3.44 (95% CI 1.67-7.09) for obese men with BMI > or = 33 compared with lean men with BMI < 23.0. Among men > or = 65 years of age, the association between BMI and risk of coronary heart disease was much weaker. However, in this age group, the waist-to-hip ratio was a much stronger predictor of risk (relative risk = 2.76, 95% CI 1.22-6.23 between extreme quintiles). These results suggest that for younger men, obesity, independent of fat distribution, is a strong risk factor for coronary heart disease. For older men, measures of fat distribution may be better than body mass index at predicting risk of coronary disease. PMID- 7771451 TI - Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40-64 years. AB - Although 40% of US women indicate they are currently trying to lose weight, the association between intentional weight loss and longevity is unknown. The authors analyzed prospective data from 43,457 overweight, never-smoking US white women aged 40-64 years who in 1959-1960 completed a questionnaire that included questions on weight change direction, amount, time interval, and intentionality. Vital status was determined in 1972. Proportional hazards regression was used to estimate mortality rate ratios for women who intentionally lost weight compared with women who had no change in weight. Women who died within the first 3 years of follow-up were excluded. Analyses were stratified by preexisting illness and adjusted for age, beginning body mass index, alcohol intake, education, physical activity, and health conditions. In women with obesity-related health conditions (n = 15,069), intentional weight loss of any amount was associated with a 20% reduction in all-cause mortality, primarily due to a 40-50% reduction in mortality from obesity-related cancers; diabetes-associated mortality was also reduced by 30-40% in those who intentionally lost weight. In women with no preexisting illness (n = 28,388), intentional weight loss of > or = 20 lb (> or = 9.1 kg) that occurred within the previous year was associated with about a 25% reduction in all-cause, cardiovascular, and cancer mortality; however, loss of < 20 lb (< 9.1 kg) or loss that occurred over an interval of > or = 1 year was generally associated with small to modest increases in mortality. The association between intentional weight loss and longevity in middle-aged overweight women appears to depend on their health status. Intentional weight loss among women with obesity-related conditions is generally associated with decreased premature mortality, whereas among women with no preexisting illness, the association is equivocal. PMID- 7771452 TI - Mortality following conjugal bereavement and the effects of a shared environment. AB - The effect of bereavement on mortality among surviving spouses was examined in a cohort of 12,522 spouse pairs belonging to a prepaid health care plan in northern California. Both spouses were examined and completed a questionnaire between 1964 and 1973, and they were followed for mortality through 1987. Between 1964 and 1987, 1,453 men (12%) and 3,294 women (26%) were bereaved; 440 bereaved men (30%) and 510 women (15%) died during follow-up. Mortality following bereavement was significantly elevated in both men and women after adjusting for age, education, and other predictors of mortality in proportional hazards analyses. The highest relative risks (RRs) of mortality occurred 7-12 months following bereavement. Among women, the RR was 1.9 (95% confidence interval (CI) 1.35-2.71) 7-12 months after bereavement. Among men, the effect of bereavement interacted with prior health status as follows: In men with few health problems, the RR of mortality was 2.12 (95% CI 1.42-3.17); men with many health problems had a RR of 1.56 (95% CI 0.98-2.55) 7-12 months after bereavement. In both men and women, the RR declined after the first year of bereavement but remained above 1.0 for more than 2 years after bereavement. The addition of terms reflecting the influence of the other spouse's characteristics and behaviors did not alter the RR of mortality, indicating no effect of a shared unfavorable environment on mortality following bereavement. PMID- 7771454 TI - Air pollution and lung cancer in Trieste, Italy. AB - To investigate the relation between air pollution and histologic type of lung cancer, the authors conducted a case-control study among men who had died in Trieste, Italy, from 1979 to 1981 and from 1985 to 1986. Through the local autopsy registry, 755 cases of lung cancer and 755 controls were identified. Information on smoking habits, occupation, and place of residence was obtained from each subject's next of kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Logistic regression was used to evaluate the effect of residence and air pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens, and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined (p = 0.022), for small cell carcinoma (p = 0.016), and for large cell carcinoma (p = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI) 0.4-1.0). The RR was 1.5 (95% CI 1.0-2.2) for residents of the center of the city and 1.4 (95% CI 1.0-2.1) for residents of the industrial area. In the center of the city, the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area, the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer. PMID- 7771453 TI - Relation of benzodiazepine use to the risk of selected cancers: breast, large bowel, malignant melanoma, lung, endometrium, ovary, non-Hodgkin's lymphoma, testis, Hodgkin's disease, thyroid, and liver. AB - Some animal data have raised the possibility that benzodiazepines influence the risk of selected cancers. With data collected in 1977-1991 in a US hospital-based study, the authors assessed the relation of benzodiazepine use to the risk of 11 cancers: breast (6,056 patients), large bowel (2,203), malignant melanoma (1,457), lung (1,365), endometrium (812), ovary (767), non-Hodgkin's lymphoma (382), testis (314), Hodgkin's disease (299), thyroid (111), and liver (37). Cases were compared with cancer controls (3,777 patients with other cancers) and noncancer controls (1,919 patients admitted for acute nonmalignant disorders). Relative risks were estimated for benzodiazepine use at least 4 days a week for at least 1 month, initiated at least 2 years before admission (sustained use) by multiple logistic regression with control for confounding factors. Results derived with noncancer controls were similar to those derived with cancer controls. For sustained benzodiazepine use relative to no use, relative risk estimates for all 11 cancers were compatible with 1.0 at the 0.05 level of significance. Relative risk estimates for durations of at least 5 years were also compatible with 1.0, with the exceptions of an increased estimate, of borderline statistical significance, for endometrial cancer, and a decreased estimate for ovarian cancer. Relative risk estimates both for sustained use that continued into the 2-year period before admission and for sustained use that ended up to > or = 10 years previously were compatible with 1.0, suggesting a lack of tumor promotion and no increase in the risk after a latent interval. Results were also null for diazepam, chlordiazepoxide, and other benzodiazepines considered separately. The results suggest absence of association between benzodiazepine use and the cancers considered, with the evidence stronger for the cancers with larger numbers of subjects. The similarity of results derived with cancer and noncancer controls suggests that benzodiazepines do not influence the risk of cancer as a whole. PMID- 7771455 TI - Association of medically treated depression and age at natural menopause. AB - Between October 1989 and November 1992, the authors surveyed approximately 10,000 women between 45 and 54 years of age residing in western metropolitan Boston and selected as cases all women naturally menopausal before age 40 and a sample of women naturally menopausal between ages 40 and 46. Controls were a random sample of women who were premenopausal or naturally menopausal after age 47. Based on the results of an in-person interview to assess past reproductive and medical history, 14% of 344 cases compared with 6% of 344 controls reported a history of medically treated depression at least 1 year prior to menopause or comparable reference age in controls (adjusted odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.3). The association of medically treated depression and early menopause was greatest in women naturally menopausal before age 40 compared with their age-and residence-matched controls (OR = 6.6, 95% CI 0.7-58.9) and in women who reported a history of medically treated depression that required more than 3 years of treatment (OR = 4.0, 95% CI = 1.3-12.0). This is the first study to suggest a link between a self-reported history of medically treated depression and early menopause. Additional studies are necessary to clarify the basis for this association. PMID- 7771456 TI - Comparison of birth weight distributions between Chinese and Caucasian infants. AB - To assess the reasons for the Chinese-Caucasian differences in birth weight distributions, a cohort study was carried out involving 18,665 Caucasian and 1,597 immigrant Chinese infants born at Montreal's Royal Victoria Hospital from January 1978 to March 1990 and 1,862 native Chinese infants born at Hefei Maternal and Infant Hospital in Hefei, People's Republic of China, from September 1990 to August 1991. Mean (standard deviation) birth weights in grams were 3,369 (567), 3,195 (493), and 3,171 (428) (p < 0.01 for differences in mean and variance), and mean (standard deviation) fetal growth ratios (ratio of observed birth weight to average birth weight at the same gestational age) were 0.994 (0.124), 0.963 (0.114), and 0.935 (0.112) (p < 0.01 for differences in mean and variance), respectively, in the Caucasian, immigrant Chinese, and native Chinese groups. No important or consistent Chinese-Caucasian differences in gestational age were found. When mothers with extreme values for demographic, anthropometric, nutritional, and lifestyle determinants of fetal growth were excluded, the mean fetal growth ratio in Caucasian infants remained significantly higher (p < 0.01), but the standard deviations became more similar (p > 0.05): Mean (standard deviation) fetal growth ratios were 1.001 (0.111), 0.966 (0.108), and 0.946 (0.114), respectively. The race-specific rate of growth differed according to period of gestation, with Chinese infants showing more rapid fetal growth early in the third trimester but slower growth near and after term. The authors conclude that the lower mean birth weight in Chinese infants is due to differences in fetal growth (rather than gestational duration) and by their inherently slower growth at or after term. The tight distribution of birth weight among the Chinese is caused partly by their reduced exposure to extremes of maternal determinants of fetal growth (mediated largely by environmental mechanisms) and partly by their inherently different growth pattern, with faster growth at earlier gestations but slower growth at later gestations. PMID- 7771457 TI - Outcome of very low birth weight infants in industrialized countries: 1947-1987. AB - Neonatal intensive care has led to a progressive improvement in the survival of very low birth weight (VLBW, < 1,500 g) infants. However, it has not been established whether there has been a simultaneous increase or decrease in the prevalence of handicapping conditions in this group of children. To explore this question, a meta-analysis was performed using outcome data of 32 developmental studies of VLBW infants born in industrialized countries between 1947 and 1987. The authors' results show that the proportion of VLBW infants who survived and had an intact outcome progressively increased between 1947 and 1987--from 147 per 1,000 live births in the period 1947-1965 to 498 per 1,000 in the period 1980 1987 (p < 0.01). The prevalence of major handicapping conditions for the subset of VLBW infants who weighed < 1,000 g at birth increased, resulting from the increasing survival rates. However, the prevalence of major handicapping conditions among all children with VLBW decreased from 147 per 1,000 live births in 1947-1965 to 45 per 1,000 in 1980-1987 (p = 0.02). The authors' meta-analysis suggests that improved survival of VLBW infants has not been accompanied by an increase, but more likely a decrease, in the prevalence of handicapping conditions in this birth weight group. PMID- 7771459 TI - Re: "Menstrual cycle patterns and risk of breast cancer". PMID- 7771460 TI - Re: "Risk attribution and tobacco-related deaths". PMID- 7771458 TI - Reliability of reports of sexual behavior: a study of married couples in rural west Africa. AB - A heterosexual partners survey in rural Senegal, Africa, was carried out in 1992 to evaluate the reliability of self-reported answers about sexual practices. The authors followed 62 married couples weekly during a 5-week period to assess the level of agreement 1) between answers made by members of the same couple but collected separately, 2) between retrospective reporting of sexual activity during the last 4 weeks versus weekly reporting of sexual activity during 4 weeks, and 3) between answers to a set of identical retrospective questions asked 5 weeks apart. Reports over recent and short periods of time such as 7 days are reliable: The dates of sexual acts with spouse reported during the weekly interviews were concordant between members of a couple at 0-day or 1-day intervals in 72% of cases. The concordance of weeks reported with or without intercourse was also high. Reports over longer periods of time are less reliable: The comparison of retrospective reports versus weekly reports regarding mean number of sexual acts during the last 4 weeks shows a clear overreporting that was higher among men (4.5 vs. 2.7 sexual acts) than among women (3.7 vs. 2.7). PMID- 7771461 TI - Treatment of aggressive non-Hodgkin's lymphoma in the elderly. AB - A nonanthracycline-containing chemotherapeutic combination for the treatment of intermediate and high-grade non-Hodgkin's lymphoma was evaluated. Thirty-four consecutive and previously untreated patients, with a median age of 75 (range 54 86) years, with aggressive lymphoma, received daily etoposide (60 mg/m2 intravenous infusion [IVI]), cytosine arabinoside (50 mg/m2 subcutaneously), and methylprednisolone (60 mg/m2 IVI) on each of 5 consecutive days. Individuals with limited disease (stages I and II) (n = 9) received six, 3-day cycles of the same therapy and involved field radiation (36 Gy in 20 fractions) between the third and fourth courses. Patients with disseminated lymphoma (n = 25) received 10 cycles over 8 months of the same combination, with the addition of methotrexate (200 mg/m2 on days 8 and 15), followed by leucovorin rescue (10 mg/m2 orally every 6 hr for 8 doses). Of the 34 patients, 44% entered complete remission (CR), and 7 died before completing the first cycle of chemotherapy. Fifty-six percent of the patients with limited disease and 40% with disseminated lymphoma (P > 0.05) achieved CR. For all patients, median survival was 14 months (range 3 days- > 54 months), this being 12 and 15 months, respectively. For the entire population of responding patients, median survival has not been reached at a median follow-up of 39 months, while the median CR duration is 21 months. Ten of the 15 responders are alive in unmaintained CR at a median of 41 (range 30-54) months. Myelotoxicity was the major side effect, leading to adjustments in dose and schedule in two-thirds of the patients, although treatment changes did not affect outcome. Of the 15 deaths that occurred in this trial, in 53.3% it was unrelated to lymphoma or its therapy. Four patients that had achieved CR died of cardiovascular events (n = 2) or of progressive second malignancies (n = 2). It is concluded that cytosine arabinoside in combination regimens is effective in selected patients; this is particularly relevant in the elderly. PMID- 7771462 TI - Peripheral blood neutrophil morphology reflects bone marrow dysplasia in myelodysplastic syndromes. AB - Dysplastic features of cells in peripheral blood and bone marrow were studied in 51 patients with myelodysplastic syndromes (MDS) to evaluate the significance of the degree of neutrophil granulation (G-score) and the percentage of pelgeroid polymorphs (ppp) in the peripheral blood, as indices of dysplastic changes in the bone marrow. There was a good correlation between peripheral blood and bone marrow findings, both for G-score figures (r = 0.92, P < 0.01) and ppp (r = 0.82, P < 0.01). Significantly lower G-score figures were found among patients with an increased percentage of bone marrow blasts (P < 0.05), while high ppp correlated with the presence of ring sideroblasts, the degree of bone marrow fibrosis, and findings of complex chromosomal abnormalities. Patients with a high degree of bone marrow dysplasia had significantly lower G-score (P < 0.01) and significantly higher ppp (P < 0.05) figures, than those with less pronounced myelodysplasia. In addition, extreme hypogranulation (G-score < 150) or very high ppp (> or = 20%) was generally a sign of bi- and tri-lineage dysplasia in the bone marrow. The results thus show that quantitative estimation of peripheral blood polymorph dysplasia by G-score figures and ppp seems to reflect the total degree of bone marrow dysplasia in MDS and may serve as a complement to bone marrow evaluation when the diagnosis of MDS is difficult. PMID- 7771464 TI - Hb Lepore (Pylos)/Hb S compounds heterozygosity in two Greek families. AB - We have studied three compound heterozygotes for Hb Lepore ("Pylos")/HbS hemoglobin, a combination quite uncommon in the literature. It is of interest that while two of these cases are clinically similar to those thus far reported, the third one is free of symptoms and the diagnosis was put incidentally. This mild condition may be due to the high level of fetal hemoglobin produced. PMID- 7771463 TI - Cobalamin-dependent metabolism in chronic myelogenous leukemia determined by deoxyuridine suppression test and the formiminoglutamic acid and methylmalonate excretion in urine. AB - The cobalamin metabolism in chronic myelogenous leukemia (CML) was evaluated in 18 newly diagnosed and untreated patients by formiminoglutamic acid (FiGlu) and methyl malonic acid excretion (MMA) tests. A deoxyuridine (dU) suppression test of bone marrow cells was compared in patients with acute myelogenous leukemia (N = 5), myelodysplastic disease (N = 3), untreated pernicious anemia (N = 16), folate deficiency (N = 7), and a hospital reference group without signs of cobalamin or folate deficiency (N = 22). All had normal MMA excretion but 3 of 15 patients had increased FiGlu excretion. In vitro thymidine uptake in bone marrow cells of CML patients were lower (mean 40 fmol/106 cells) than pernicious anemia patients (115 fmol/106 cells). Methotrexate (MTX) increased the uptake in all cases. Addition of formyl-THF, methyltetrahydrofolate (methyl-THF), and pteroylglutamic acid (PGA) tended to normalize the effect of MTX. In pernicious anemia methyl-THF only decreased the uptake in combination with CN-Cbl. dU suppression values were significantly higher (6.3%) in CML than in the reference group (4.4%), but significantly lower than in pernicious anemia (41.6%) and folate deficiency (28.5%). The dU suppression values in bone marrow cells of CML patients correlated significantly with the transferrin saturation. In buffy coat cells dU suppression values were even higher (9.3%) than in bone marrow cells of the same CML patients. Addition of folate forms and CN-Cbl did not change the dU suppression values in CML, as it did in pernicious anemia. MTX increased dU suppression values significantly in all patients, but more in CML (64.5%) than in pernicious anemia (48.6%) and controls (49.8%). The MTX effect was to some extent neutralized by folate analogues with formyl-THF as the most effective followed by methyl-THF and lastly PGA. Methyl-THF also neutralized MTX in pernicious anemia, but its effect was certainly enhanced by addition of CN-Cbl. Thymidine uptake and dU suppression patterns were not significantly changed in CML after treatment with busulfan for 1 week or in accelerated phase. We concluded that signs of cobalamin or folate deficiency (apart from one patient) cannot be demonstrated in untreated CML. However, dU suppression was significantly increased and more so in circulating myeloid cells than in bone marrow. This indicates a deranged metabolism of deoxynucleotides which is independent of cobalamin and folates, and a difference between bone marrow cells and circulating cells. dU suppression is a valuable indicator of cobalamin deficiency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7771465 TI - Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis. AB - The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine. PMID- 7771466 TI - Pretreatment fibrinogen levels are associated with response to chemotherapy in patients with small cell carcinoma of the lung: Department of Veterans Affairs Cooperative Study 188. AB - Small cell carcinoma of the lung (SCCL) responds commonly to combination chemotherapy but resistance to therapy follows. Prior reports have suggested that a relationship may exist between plasma fibrinogen levels and response to therapy in SCCL. This study was designed to determine the possible predictive value of the fibrinogen level for tumor response (chemoresistance) in SCCL. Pretreatment fibrinogen levels were correlated with outcome and response to therapy in a cohort of 119 previously untreated patients with SCCL who were admitted to VA Cooperative Study 188. Higher pretreatment fibrinogen levels at diagnosis correlated significantly with more advanced stage of disease at entry (P < 0.001) and with reduced overall survival (P = 0.030). In addition, higher pretreatment fibrinogen levels were correlated significantly with a reduced likelihood of achieving subsequent disease regression with combination chemotherapy (P = 0.005). Because several clinical trials have shown that anticoagulant therapy improves tumor response rates and survival of SCCL, we postulate that tumor cell thrombin generation not only promotes SCCL growth but may also be primarily responsible for both increased fibrinogen levels and for resistance to chemotherapy. These findings provide incentive for studies of thrombin effects on the development of multidrug resistance, and for new clinical trials of more potent and specific inhibitors of thrombin that may further improve tumor response and survival in SCCL. PMID- 7771467 TI - Large molecule fraction of plasma separated with polyethylene glycol in treatment of chronic relapsing thrombotic thrombocytopenic purpura. AB - Plasma exchange and plasma infusion are effective in the treatment of patients with thrombotic thrombocytopenic purpura (TTP). It has been proposed that some component in normal plasma may be deficient in TTP patients. In this experiment normal plasma was fractionated and an effective fraction for the treatment of TTP was sought. Plasma was fractionated with 5% polyethylene glycol and a large molecule fraction was obtained which was composed mainly of proteins and lipoproteins with molecules larger than that of IgG. The fraction was dissolved in physiological saline and infused in two patients with chronic relapsing TTP who had been successfully treated periodically with plasma infusion. Peripheral platelet counts and serum LDH levels were measured, and the efficacy of the treatment was assessed. Infusion of the large molecule fraction elevated platelet counts and lowered the LDH level. However, the efficacy of the large molecule fraction was 25 to 50% that of plasma. Components in the fraction may have been inactivated partially during preparation. We propose that the large molecule fraction contains factors which are effective in some patients with TTP. PMID- 7771468 TI - Familial myelodysplastic syndrome with onset late in life. AB - A family is described in which three, and possibly four members, namely, the propositus, two paternal uncles, and possibly his paternal grandfather, developed a myelodysplastic syndrome (MDS) after the age of 60 years. This late onset resembles sporadic cases which are commoner in older age, rather than the previously reported familial cases most of whom have been children or young adults. The three affected members had megaloblastoid bone marrows with an increased proportion of bone marrow blasts and developed progressive bone marrow failure without leukemic transformation. The propositus showed a dramatic but temporary response to GM-CSF therapy but eventually became unresponsive with a marked increase in bone marrow reticulin and reduction in hemopoietic elements. Affected members had no recognisable bone marrow cytogenetic abnormality but the pattern of inheritance and similarity in clinical features suggest an inherited genetic defect which predisposes to the development of MDS. PMID- 7771469 TI - Transformation of chronic myelomonocytic leukemia to acute lymphoblastic leukemia: case report and review of the literature of lymphoblastic transformation of myelodysplastic syndrome. AB - If chronic myelomonocytic leukemia (CMML) transforms into an acute leukemic phase, the blast crisis is invariably myeloid. Occasionally, the other subtypes of myelodysplastic syndrome (MDS) (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation) have been noted to transform into acute lymphoblastic leukemia (ALL). We now report a case of CMML that transformed into ALL and we review the literature of 13 other cases of MDS with ALL transformation. Such cases provide suggestive clinical evidence that MDS can involve a pluripotent stem cell. PMID- 7771470 TI - Sickle cell anemia and beta-gene cluster haplotypes in Cuba. AB - We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.511, 2 df, P = 0.001). When the whole sample of 198 chromosomes (SS, SC, and S/beta thal) is considered, we find that the beta s chromosome is linked 51% to the Benin haplotype, 41% with the Bantu, and 8% with the Senegal. After adjusting for the different frequencies of beta s in Africa, these numbers would predict the port of origin to be 16% from Atlantic West Africa, 37.3% from Central West Africa, and 46% from Bantu-speaking Africa. This is in direct contradiction with the historical record that establishes a higher percentage from Bantu-speaking Africa (55%) and a much lower percentage from Senegal (3.4%). The overall conclusions from these findings is that there is a loss of Bantu haplotypes in sickle cell syndromes in Cuba, particularly among adults, and that there is an excess of Senegal haplotype, also among adults. These differences might reflect the differential survival and severity of the sickle cell disease linked to these haplotypes. PMID- 7771471 TI - Treatment of platelet alloimmunization with intravenous immunoglobulin in a child with aplastic anemia. AB - A 9-year-old girl with severe refractory aplastic anemia had become refractory to platelet transfusion due to platelet alloimmunization. As a result, a huge right parieto-temporo-occipital cerebral hematoma and a subarachnoid hemorrhage subsequently occurred. Intravenous immunoglobulin (IVIG) (Green Cross, Taiwan) at a dose of 0.4 g/kg/day for 5 days, followed by another 3 doses during the following 5 days, and combined with large-dose platelet transfusions effectively controlled the bleeding by elevating the platelet count to above 100 x 10(3)/mm3. The patient soon recovered with only a mild sequela. Two months later, because of multiple caries and a periodontal abscess, dental extraction needed to be performed. IVIG (0.4 g/kg/day x 6 days) enabled surgery to proceed by elevating the platelet count to above 55 x 10(3)/mm3, and no bleeding complications occurred during or after the procedure. The potential benefit of high-dose IVIG in modulating platelet alloimmunization is a result of increasing the survival of transfused platelets. Thus, this therapy is recommended when patients with platelet alloimmunization have critical bleeding episodes or undergo surgical procedures. PMID- 7771472 TI - Proposal for a type IV blast in the FAB classification. PMID- 7771473 TI - Giant dysplastic neutrophils: possible morphologic evidence of in vivo differentiation of leukemia in acute myeloblastic leukemia. PMID- 7771474 TI - Serous fat atrophy with leukopenia in severe anorexia nervosa. PMID- 7771475 TI - Pure red cell aplasia and cyclosporine. PMID- 7771476 TI - Bartter's syndrome: the unsolved puzzle. AB - Bartter's syndrome is a congenital abnormality characterized by metabolic alkalosis [corrected], hyperreninemic hyperaldosteronism, and hypokalemia. Most patients present early in life with symptoms such as muscle weakness and polyuria, which may be attributed to potassium depletion. Despite the hyperaldosteronism, the patients tend to be normotensive, which is at least partially explained by vascular hyporesponsiveness to pressor hormones. Numerous studies have documented increased renal excretion of prostaglandins. Several different patterns of aberrant renal ion transport have been observed in patients with the syndrome, suggesting that it actually may represent a family of related but distinct tubular disorders. Therapeutic approaches to Bartter's syndrome include potassium supplementation, prostaglandin synthesis inhibitors (nonsteroidal anti-inflammatory agents), aldosterone antagonists, and converting enzyme inhibitors. During the first two decades following its initial description, Bartter's syndrome was the focus of widespread interest, based on the likelihood that its investigation might provide insight into the normal functioning of the renin-angiotensin-aldosterone and prostanoid hormone systems. During the past decade, however, little additional progress has been made in Bartter's syndrome, and its patho-physiology remains poorly understood. PMID- 7771477 TI - Normal prostaglandinuria E2 in Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome. AB - In familial Bartter's syndrome, hyperprostaglandinuria is considered a constant feature and prostanoid synthetase inhibition often positively influences the disease course. The urinary calcium excretion distinguishes two clinically and biochemically different variants, namely, classic Bartter's syndrome (normocalciuric or hypercalciuric variant; urinary calcium to creatinine > or = 35.3 mg/mg 10(-3)) and Gitelman's syndrome (hypocalciuric variant; urinary calcium to creatinine < 35.3 mg/mg 10(-3)). In the hypocalciuric variant of Bartter's syndrome prostanoid synthetase inhibition is of little benefit. Since the production of prostanoids has not been extensively studied in Gitelman's syndrome, the urinary excretion of prostaglandin E2 was assessed by radioimmunoassay in 11 untreated patients with Gitelman's syndrome (aged 10 to 21 years; five females and six males) and in 11 healthy controls (aged 11 to 20 years; five females and six males). The urinary excretion of prostaglandin E2 was similar in both study groups. The study provides the rationale for the poor effect of prostanoid synthetase inhibition in the hypocalciuric variant of Bartter's syndrome. The assessment of urinary excretion of prostaglandin E2 does not represent a diagnostic sine qua non in the context of familial Bartter's syndrome. PMID- 7771478 TI - Liddle's syndrome, an underrecognized entity: a report of four cases, including the first report in black individuals. AB - Liddle's syndrome, a rare cause of hypokalemic hypertension, is characterized by a renal tubular sodium channel defect resulting in excessive sodium absorption and concomitant potassium wasting. In this disorder, although the clinical manifestations resemble primary aldosteronism, serum and urine aldosterone are suppressed. The syndrome is transmitted in an autosomal dominant pattern. It has been reported previously in white and oriental populations but not in the black individuals. We identified four patients (two of whom are black) in our nephrology clinic, with severe hypokalemic hypertension not correctly diagnosed for several years. All patients underwent an extensive work-up for secondary hypertension because of persistent severe hypertension (average blood pressure, 210/130 mm Hg) despite high-dose multi-drug therapy. Primary aldosteronism was excluded because of low serum aldosterone. Cushing's syndrome, pheochromocytoma, renal artery stenosis, and enzymatic deficiencies of cortisol synthesis (11 beta hydroxylase, 17 alpha-hydroxylase, 5 beta-reductase, and 11 beta-hydroxysteroid dehydrogenase) were ruled out with extensive endocrine and radiologic studies. Once the diagnosis of Liddle's syndrome was suspected, all patients were treated with either triamterene or ameloride, with resolution of hypokalemia and correction of hypertension occurring within 5 to 7 days. Our findings suggest that Liddle's syndrome can occur in the black population. Although the actual incidence of this syndrome remains unknown, it may be significantly more common than we are led to believe since it is inherited in a Mendelian pattern. Whether there is a subset of low-renin, salt-sensitive black hypertensive patients who have the same or similar sodium channel defect remains to be elucidated. PMID- 7771479 TI - Clinical factors associated with urinary albumin excretion in type II diabetes. AB - Clinical factors associated with urinary albumin excretion (UAE) in type II diabetes are less well known than in type I diabetes. To examine the factors associated with UAE in type II diabetes, 933 Appropriate Blood Pressure Control in Diabetes Trial patients were classified according to UAE status: normoalbuminuria (< 20 micrograms/min), microalbuminuria (20 to 200 micrograms/min), and macroalbuminuria (> 200 micrograms/min). The class of UAE was then correlated with various clinical factors. Using univariate analyses, Hispanic ethnicity, African-American race, male gender, poor glycemic control, insulin use, long duration of diabetes, dyslipidemia, diastolic and systolic hypertension, smoking, and obesity were significantly correlated with microalbuminuria and macroalbuminuria. Using multivariate logistic regression analyses controlling for diabetes duration, glycosylated hemoglobin, gender, and race, the most significant predictors of microalbuminuria and macroalbuminuria were systolic hypertension, body mass index, high-density lipoprotein cholesterol, insulin use, and smoking pack-years. Of these factors, several are potentially reversible with aggressive intervention. PMID- 7771480 TI - Primary focal segmental glomerular sclerosis in adults: prognostic value of histologic variants. AB - Primary focal segmental glomerular sclerosis (FSGS) is a clinicopathologic syndrome in which variable amounts of proteinuria are associated with the renal biopsy finding of segmental glomerular scarring in some, but not all, of the glomeruli. Additional histologic features have been described in FSGS, including the position of the scar relative to the vascular and tubular pole of the glomerulus, foam cells, hyalinosis, mesangial deposits of immunoglobulin M, diffuse mesangial hypercellularity, glomerular visceral epithelial cell hyperplasia and hypertrophy, and the extent of associated interstitial fibrosis and tubular atrophy. We performed a retrospective study on 81 patients with biopsy-proven, primary FSGS to determine whether any of the histologic features of FSGS correlated with renal function at the time of biopsy and the incidence of end-stage renal disease at follow-up. Sixty patients were nephrotic and 21 had nonnephrotic proteinuria. Only the degree of interstitial fibrosis correlated with the initial serum creatinine (r = 0.536) and none of the histologic features predicted the presence of nephrotic-range proteinuria at the time of biopsy. Segmental scars involved 21% +/- 14% of the glomeruli per biopsy specimen, but their position within the glomerulus was uniform in only 13% of the cases. Diffuse mesangial hypercellularity was present in 17% of the biopsy specimens, and glomerular epithelial cell lesions were present in 57% of the biopsy specimens. Multivariate analysis showed that only the degree of interstitial fibrosis predicted end-stage renal disease in all 81 patients and in the 60 patients with nephrotic-range proteinuria. The current data do not support different therapeutic approaches in primary FSGS based on histologic subtypes. PMID- 7771481 TI - Paramesangial glomerular deposits in membranoproliferative glomerulonephritis type II correlate with hypocomplementemia. AB - To gain support for a previously proposed hypothesis that nephritic factors predispose to chronic glomerulonephritis, the glomerular deposits of patients with membranoproliferative glomerulonephritis type II have been studied by electron microscopy and immunofluorescence and the results correlated with the C3 level at the time of biopsy. If, as hypothesized, circulating convertase predisposes to nephritis, finding that the glomeruli of patients hypocomplementemic at biopsy, presumably with nephritic factor-stabilized convertase in their circulation, differ from those of patients normocomplementemic at biopsy would suggest that circulating convertase in some way alters the glomerulus. Among 25 biopsy specimens from 12 patients, hypocomplementemia did not correlate with capillary loop deposits, but there was strong correlation with deposits in the paramesangial region as detected by electron microscopy. Of 11 patients who were normocomplementemic at biopsy, none had paramesangial deposits in their glomeruli. Of 14 patients who were hypocomplementemic at biopsy, deposits were present in the paramesangium in 12 patients (P < 0.001). The deposits were either on both sides of the paramesangial segment of the basement membrane (waist basement membrane related) or in apposition to the paramesangial basement membrane in a subepithelial position only. The detection of paramesangial deposits in the ultrastructure correlated with the detection of C3-containing mesangial granules by immunofluorescence; immunoglobulin G, C5, properdin, and factor B could not be demonstrated in these granules. The study identifies the mesangial deposits described by others in membranoproliferative glomerulonephritis type II as paramesangial deposits and, more importantly, demonstrates that their presence correlates closely with hypocomplementemia. It is likely that these deposits in some way result from the presence in the circulation of convertase stabilized by the nephritic factor of the amplification loop. PMID- 7771482 TI - A review of therapeutic studies of idiopathic membranous glomerulopathy. AB - The treatment of idiopathic membranous glomerulopathy remains an enigma. We have reviewed many of the important clinical trials concerning membranous glomerulopathy using a meta-analysis and a secondary pooled analysis to test the effects of corticosteroid or alkylating, therapy compared with no treatment on renal survival and complete remission of the nephrotic syndrome. A search was performed using MEDLINE (1968 through 1993) for articles on idiopathic membranous glomerulopathy and glomerulonephritis. Bibliographies of articles were reviewed for completeness. Sixty-nine articles were reviewed. Meta-analysis was performed for four trials that evaluated corticosteroids compared with no treatment and for three trials that evaluated alkylating therapy compared with no treatment. Pooled analysis was performed on randomized and prospective studies (10 studies) and then with 22 case series added. All studies evaluated renal biopsy-proven disease. Meta-analysis was performed on the relative chance of being in complete remission for each study. Renal survival could be evaluated by pooled analysis only. For pooled analyses, Cox's proportional hazard and logistic regression models were used to test the effect of therapy on renal survival and the nephrotic syndrome, respectively. Data concerning gender, nephrotic syndrome, and geographic region were used in all statistical models. Evaluation of renal survival revealed no differences by treatment group (P > 0.1). By meta-analysis, the relative chance of complete remission was not improved for corticosteroid treated patients (1.55; 95% confidence interval, 0.99 to 2.44; P > 0.1), but was improved for patients treated with alkylating agents (4.8; 95% confidence interval, 1.44 to 15.96; P < 0.05) when compared with no treatment. Pooled analysis of randomized and prospective studies, as well pooled analysis with all studies, supported the findings of the meta-analysis. Corticosteroids or alkylating therapy did not improve renal survival in idiopathic membranous glomerulopathy. Complete remission of the nephrotic syndrome was observed more frequently with the use of alkylating agents. PMID- 7771483 TI - Renal biopsy as an outpatient procedure. AB - We evaluated the safety and efficacy of outpatient renal biopsy by prospectively comparing outpatient and inpatient renal biopsies in which patients were given the choice between having the procedure as an inpatient or an outpatient. Three hundred fifty renal biopsies were performed between January 1992 and August 1994; 118 patients had the procedure as an outpatient and 232 patients had the procedure with discharge planned for the following day. There was no difference between the two groups in terms of patient age, sex, or renal function. The complication rate for the two groups was not significantly different, with two inpatients having loin pain and one having macroscopic hematuria compared with one outpatient having loin pain and one having macroscopic hematuria. The biopsies provided samples of comparable size. We conclude that outpatient renal biopsy is a safe procedure and provides adequate tissue samples. PMID- 7771484 TI - Effect of administering calcium carbonate to treat secondary hyperparathyroidism in nondialyzed patients with chronic renal failure. AB - We administered calcium carbonate orally to determine its safety and efficacy in treating nondialyzed patients with mild to moderate renal failure and secondary hyperparathyroidism. Twenty patients with chronic renal failure (creatinine clearance levels ranging from 7.9 to 42.7 mL/min) participated in this study. After a 6-month control period, 3 g calcium carbonate was administered daily for 6 months. We studied the effect for another 6 months after discontinuation of the regimen. We found that serum-intact parathyroid hormone was suppressed from 183 +/- 149 pg/mL to 85 +/- 61 pg/mL (P < 0.05) by treatment. This suppression was achieved with no increase in serum concentrations of 1,25(OH)2D3. Serum phosphorus levels decreased from 3.4 +/- 0.7 to 3.0 +/- 0.7 mg/dL (P < 0.01) and Ca2+ concentration increased significantly from 2.40 +/- 0.12 mEq/L to 2.57 +/- 0.08 mEq/L (P < 0.001) at 6 months. These changes were reversed after the 6-month period of withdrawal from calcium carbonate. Deterioration of renal function was not exacerbated by the therapy. Calcium carbonate administration also suppressed the serum concentrations of alkaline phosphatase and osteocalcin, indicating that improvement of hyperparathyroid bone disease is possible without a vitamin D3 supplement at an earlier stage of renal failure. Thus, administration of 3 g oral calcium carbonate daily was highly effective in treating secondary hyperparathyroidism in patients with mild to moderate renal failure. PMID- 7771485 TI - Determination of protein catabolic rate in patients on chronic intermittent hemodialysis: urea output measurements compared with dietary protein intake and with calculation of urea generation rate. AB - We assessed the agreement between different methods of determining protein catabolic rate (PCR) in hemodialysis patients and the possible influence of postdialysis urea rebound and the length of the interdialytic interval on the PCR determination. Protein catabolic rate derived from measured total urea output was compared with recorded daily protein intake (DPI) and calculated urea generation rate (G), calculated by the interdialytic increase in serum urea and an estimated urea distribution volume using either the Watson equation or 58% of postdialysis body weight, and by single-pool urea kinetic modelling. In 16 patients PCR derived from calculated G by fixed urea distribution volume showed a significant decrease with blood samples obtained 10 minutes after dialysis onward as compared with immediately after dialysis, leading to an approximately 6% decrease at 60 minutes. Protein catabolic rate values derived from blood samples taken 15 to 60 minutes after dialysis were not significantly different. Urea kinetic modelling led to a significant increase in calculated PCR with samples from 5 minutes after dialysis onward and a total increase by 11.5% at 60 minutes. Different methods for determining PCR were compared in 13 clinically stable outpatients treated with conventional hemodialysis on cellulose acetate membrane dialyzers during 1 week. The mean PCR calculated from measured total urea output was 61.3 g/24 hr (range, 43.7 to 83.2 g/24 hr). Assessment of DPI as compared with PCR calculated from measured total urea output was lower by 7.5% (95% confidence intervale [CI], 1.4 to 17.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771486 TI - On complement net generation in fast hemodialysis: are high blood flow rates bioincompatible? AB - Arterial and venous concentrations of complement (C3a) and leukocyte count were determined in 17 patients during 201 hemodialysis sessions by 12 different treatment modes executed in random order using cuprophan, hemophan, or polyamide membranes with small or large membrane areas and high blood flow (Qb) (400 mL/min) for 2 hours or low Qb (200 mL/min) for 4 hours. With all membrane types, the number of leukocytes was significantly higher after 120 minutes of dialysis and by the end of treatment at high Qb compared with low Qb. C3a concentrations (microgram/mL) in the arterial and venous blood lines were significantly higher during cuprophan dialysis compared with hemophan and polyamide dialyses (P < 0.001). In addition, the net generation of C3a (microgram/min) was significantly higher during hemodialysis with cuprophan compared with hemophan and polyamide (P < 0.001). After 2 hours at high Qb for each of the three membranes, the net generation of C3a was significantly higher compared with low Qb (P < 0.05 for all comparisons). Possible reasons for the increase in the net generation of C3a (microgram/min) at high Qb are less protein deposition on the membrane at high Qb or the fact that the protein coat is stripped off in the dialyzer, thereby recreating a less biocompatible surface. Hemodialysis at high Qb may thus be less biocompatible than dialysis at low Qb. PMID- 7771487 TI - The efficacy of erythropoietin in human immunodeficiency virus-infected end-stage renal disease patients treated by maintenance hemodialysis. AB - The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771488 TI - Oral calcium carbonate administration ameliorates the progression of renal failure in rats with hypertension. AB - Oral calcium supplementation is reported to have phosphate-binding and antihypertensive effects. Since both phosphate binders and antihypertensive agents are reported to attenuate renal injury, we studied the effect of oral calcium carbonate (CaCO3) administration on the course of renal deterioration using doxorubicin-induced renal failure in rats treated with deoxycorticosterone acetate and salt for 10 weeks. Rats were divided into four groups: the CaCO3 (6.0 g/kg/d) group (n = 12), the aluminum hydroxide (Al(OH)3; 6.0 g/kg/d) group (n = 11, as a phosphate-binder control), the hydralazine (10 mg/kg/d) group (n = 11, as an antihypertensive control), and the control group (n = 12). All agents were given as a mixed chow diet. Blood pressure and urinary protein excretion progressively increased in the control rats. CaCO3 and hydralazine lowered blood pressure, but Al(OH)3 did not (185 +/- 4 mm Hg, control; 160 +/- 5 mm Hg, CaCO3; 171 +/- 8 mm Hg, Al(OH)3; 156 +/- 5 mm Hg, hydralazine at week 10). Proteinuria was reduced in the rats treated with CaCO3 and Al(OH)3 compared with those without the treatment (986 +/- 86 mg/d, control; 551 +/- 54 mg/d, CaCO3; 527 +/- 31 mg/d, Al(OH)3; and 955 +/- 68 mg/d, hydralazine at week 10). Serum phosphate concentration and calcium phosphate products also were significantly lower in both the CaCO3 and Al(OH)3 groups than in the control group. At week 10, increased serum urea nitrogen, impaired renal function, and glomerular sclerosis present in the control group were significantly attenuated in both in the CaCO3 and Al(OH)3 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771489 TI - Alterations in renal endothelin production in rats with reduced renal mass. AB - Renal endothelin-1 (ET-1) production is diminished in spontaneously hypertensive rats. An increase has been reported of renal ET-1 production associated with progression of renal disease in rats with reduced renal mass. The purpose of the present study was to investigate the evolution over time of the urinary ET-1 excretion in an experimental model of renal mass reduction not caused by renal infarction. Rats were subjected to 2/3 nephrectomy (right nephrectomy and resection of the lower left renal pole) and thereafter randomly assigned to a no treatment control group or to treatment with recombinant erythropoietin, recombinant erythropoietin plus verapamil, or recombinant erythropoietin plus enalapril. The urinary ET-1 excretion was decreased by week 16 after nephrectomy as compared with healthy animals and with the levels 6 weeks after nephrectomy. The temporal evolution of urinary ET-1 excretion in the various groups of rats showed a trend toward decrease in all groups except the one receiving enalapril. The urinary ET-1 excretion correlated directly with creatinine clearance and inversely with tubulointerstitial damage. We observed an inverse correlation between urinary ET-1 excretion and arterial blood pressure 16 weeks after nephrectomy. These results indicate that renal ET-1 production decreases with the progression of renal disease and in relation with the severity of tubulointerstitial damage. The decrease in renal ET-1 production might contribute to the development and perpetuation of renal disease-associated arterial hypertension; this situation may be favorably modified by the use of enalapril. PMID- 7771490 TI - Liddle's syndrome: a public health menace? PMID- 7771491 TI - Tumefactive megalocytic interstitial nephritis in a patient with Escherichia coli bacteremia. AB - Megalocytic interstitial nephritis is rare and primarily affects the cortex in an otherwise normal kidney. We recently encountered a patient with Escherichia coli bacteremia and oliguric acute renal failure who died of gram-negative septicemia. At autopsy, this patient's kidneys displayed typical features of megalocytic interstitial nephritis. We were able to perform special stains suggesting that the histiocytic interstitial cells originated from infiltrating macrophages. Our patient illustrates that macrophage proliferation can result in interstitial inflammation sufficiently severe to cause anuric acute renal failure. PMID- 7771492 TI - Acute interstitial nephritis associated with ticlopidine. AB - Ticlopidine, a platelet aggregation inhibitor, has been approved to decrease the risk of thrombotic stroke. We describe a 75-year-old white woman who developed acute renal failure 10 days after initiating ticlopidine therapy. A renal biopsy revealed interstitial infiltrates containing lymphocytes and eosinophils. To our knowledge this is the first report of ticlopidine-induced acute interstitial nephritis. PMID- 7771493 TI - Renal hypouricemia: prevention of exercise-induced acute renal failure and a review of the literature. AB - Isolated renal hypouricemia from defective uric acid reabsorption and/or secretion is a well-described entity, with a prevalence of 0.12% to 0.20% in Japan. It is rarely associated with exercise-induced acute renal failure (ARF). The etiology of ARF is debated. Prevention of ARF in renal hypouricemia has not been previously addressed. A 29-year-old Pakistani man had recurrent exercise induced ARF. He was found to have isolated renal hypouricemia; serum uric acid 0.5 mg/dL, 24-hour urine uric acid 472 +/- 25 mg (+/- SD), and fractional excretion of uric acid 55.2% to 69.4%. Both pyrazinamide and probenecid decreased fractional excretion of uric acid and uric acid excretion rate (UV(Urate)) in our patient, suggesting either a partial presecretory and postsecretory reabsorption defect or increased secretion. We investigated renal uric acid excretion during exercise in our patient and four control subjects. All five subjects underwent a physical fitness test (PFT). Our patient developed ARF. Uric acid excretion rate increased in our patient, from 0.48 mg/min at baseline to 1.49 mg/min 4 hours after the PFT, as did the urine uric acid to urine creatinine ratio (UUa)/UCr) (0.29 to 1.49). In the controls, UV(Urate) and UUA/UCr were unchanged after the PFT: UV(Urate) was 0.46 +/- 0.10 mg/min at baseline and 0.59 +/- 0.04 mg/min 4 hours after the PFT, while UUA/UCr was 0.30 +/- 0.04 at baseline and 0.36 +/- 0.04 at 4 hours. All five subjects took allopurinol 300 mg daily for 5 days and repeated the PFT. In our patient, allopurinol prevented the ARF as well as the exercise-induced increases in UV(Urate) (0.28 mg/min to 0.22 mg/min) and UUA/UCr (0.25 to 0.17). In the controls, the UV(Urate) and UUA/UCr responses to exercise were not altered. We conclude that increased renal excretion of uric acid during exercise was responsible for the ARF in our patient with renal hypouricemia and that successful prophylaxis with allopurinol is possible. PMID- 7771494 TI - Common variable immunodeficiency in a renal transplant patient with severe recurrent bacterial infection: a case report and review of the literature. AB - The second reported case of common variable immunodeficiency (acquired agammaglobulinemia) after renal transplantation is presented. Agammaglobulinemia presumably resulted from long-standing immunosuppression. This case and our review of the literature indicate that agammaglobulinemia is a rare event after transplantation but can be treated successfully with intravenous immunoglobulin. Additionally, hypogammaglobulinemia occurs frequently after transplantation and should be monitored and treated in appropriate clinical situations. The treatment of our patient with intravenous immunoglobulin also suggests that patients with common variable immunodeficiency can undergo renal transplantation. PMID- 7771495 TI - Lipoprotein glomerulopathy with a new apolipoprotein E phenotype. PMID- 7771496 TI - Biologic control of the tumor necrosis factor and interleukin-1 signaling cascade. AB - It is clear that activation of the proinflammatory cytokine cascade is both the cause and the consequence of renal injury. Recently, it has been appreciated that a rich network of signaling pathways contributes to modulation of tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) bioactivity, both in vitro and in vivo. Insight into the checks and balances that intervene or temper endogenous cytokine effector mechanisms has arisen from an explosion of new information on the cell biology of proinflammatory cytokines. Novel mechanisms of cytokine regulation are currently being described and hold promise for therapeutic potential: soluble cytokine receptors, endogenous receptor antagonists, and anti inflammatory cytokines such as IL-4, IL-10, and IL-13. PMID- 7771497 TI - Magnesium deficiency: pathophysiologic and clinical overview. PMID- 7771498 TI - Percutaneous transhepatic PermCath for hemodialysis vascular access. PMID- 7771499 TI - Early repolarization on scalar electrocardiogram. AB - Sixty thousand electrocardiograms were analyzed for 5 years. Six hundred (1%) revealed early repolarization (ER). Features of ER were compared with race-, age , and sex-matched controls (93.5% were Caucasians, 77% were males, 78.3% were younger than 50 years, and only 3.5% were older than 70). Those with ER had elevated, concave, ST segments in all electrocardiograms (1-5 mv), which were located most commonly in precordial leads (73%), with reciprocal ST depression (50%) in a VR, and notch and slur on R wave (56%). Other results included sinus bradycardia in 22%, shorter and depressed PR interval in 38%, slightly asymmetrical T waves in 96.7%, and U waves in 50%. Sixty patients exercised normalized ST segment and shortened QT interval (83%). In another 60 patients, serial studies for 10 years showed disappearance of ER in 18%, and was seen intermittently in the rest of the patients. The authors conclude that in these patients with ER: 1) male preponderance was found; 2) incidence in Caucasians was as common as in blacks; 3) patients often were younger than 50 years; 4) sinus bradycardia was the most common arrhythmia; 5) the PR interval was short and depressed; 6) the T wave was slightly asymmetrical; 7) exercise normalized ST segment; 8) incidence and degree of ST elevation reduced as age advanced; 9) possible mechanisms of ER are vagotonia, sympathetic stimulation, early repolarization of sub-epicardium, and difference in monophasic action potential observed on the endocardium and epicardium. PMID- 7771500 TI - Case report: lanreotide in the management of hypercalcemia of malignancy. AB - The management of hypercalcemia of malignancy (HCM) is difficult if the underlying neoplasm cannot be treated successfully. The overexpression of parathyroid hormone-related protein (PTHrP) by various neoplasms is a common mechanism of HCM and usually is a premorbid event. Current pharmacologic measures to control HCM are directed more toward inhibiting the action rather than inhibiting the secretion of PTHrP. The somatostatin congeners are a novel class of drugs that can inhibit some excessive hormonal states. In this report, the authors summarize an observation made using lanreotide, an investigational somatostatin congener, in treating a patient with a neuroendocrine neoplasm. Lanreotide administration resulted in normalizing the serum calcium levels while decreasing plasma PTHrP concentrations. The chronic administration of lanreotide produced a stable radiographic response and controlled the HCM without adverse side effects. The somatostatin congeners potentially offer another therapeutic modality in managing HCM. PMID- 7771501 TI - Case report: reversible QT prolongation with torsades de pointes in a patient with pimozide intoxication. AB - Pimozide is a diphenylpiperidine neuroleptic with well characterized cardiovascular side effects including QT prolongation. So far, life-threatening cardiac arrhythmias, in particular torsades de pointes, have not been described in patients treated with pimozide. The authors describe a patient in whom torsades de pointes developed after the ingestion of 800 mg pimozide as a suicide attempt. After intravenous treatment with lidocaine and magnesium, the patient recovered completely and the QT interval had normalized 5 days after the intoxication. Potential mechanisms leading to torsades de pointes in patients treated with pimozide are discussed. PMID- 7771502 TI - Case report: hypoglycemia secondary to a meningioma. AB - Hypoglycemia secondary to a meningioma that has not metastasized to the liver has not been reported previously. A 41-year-old woman with a spinal cord meningioma first diagnosed 5 years previously with 3 recurrences in the spinal cord resulting in 4 neurosurgical procedures was admitted with a serum glucose of 23 mg/dL. Six months before the current admission, the patient was noted to have an abdominal mass of 10 cm not present on previous computed tomography. Three months later, the mass was 15.2 cm, and on the current admission, had increased to 23 cm and encased both the aorta and inferior vena cava. A needle biopsy of this mass before referral to the authors' hospital with hypoglycemia revealed that it was a meningioma. Evaluation of the etiology of the hypoglycemia, which required continuous intravenous glucose therapy, revealed that circulating insulin, C peptide (i.e., connecting peptide), insulin-like growth factor-I (i.e., somatomedin-C) and insulin-like growth factor-II were all normal or low. Serum cortisol also was not low. Based on her endocrine evaluation, the hypoglycemia was secondary to the large mass of tumor cells, requiring a large glucose uptake to sustain its growth. After radiation therapy of 3,770 CGy to the meningioma, the patient became euglycemic without glucose supplementation. PMID- 7771503 TI - Case report: diabetic ketoacidosis in a patient with glucagonoma. AB - The development of diabetic ketoacidosis is an unusual complication of a glucagon secreting pancreatic islet cell neoplasm, with only four reported cases in the literature. In this article, the authors report on a 46-year-old woman with a glucagonoma cosecreting pancreatic polypeptide, somatostatin, and serotonin diagnosed 8 months before the onset of diabetic ketoacidosis. She was treated with hydration, insulin, and octreotide, with improvement in her clinical course and a decrease in the glucagon, pancreatic polypeptide, and chromogranin A plasma levels. With the addition of weekly 5-FU, she has maintained a partial radiographic response and has had no further episodes of diabetic ketoacidosis for a 4.5-year period. Diabetic ketoacidosis can develop in the presence of a glucagonoma, and the pathophysiology remains unknown. PMID- 7771504 TI - Southwestern Internal Medicine Conference: mastocytosis: developments during the past decade. AB - Mastocytosis is a spectrum of disorders characterized by an aberrant proliferation of tissue mast cells. Although this disease process often affects the skin, it may involve multiple organs. The clinical disorder varies according to patient age, the clinical manifestations demonstrated, and the extent of the mast cell proliferative process. A myriad of clinical symptoms occur, and these may be localized to the organ system involved or may be systemic, depending on whether there is local or generalized mast cell mediator release. Diagnosis includes the demonstration of increased tissue mast cells in involved organs as well as increased levels of biochemical mediators. Patients with cutaneous involvement only have the best prognosis. Treatment is directed toward stabilizing mast cell mediator release and blocking the effects of those mediators generated. PMID- 7771505 TI - Southwestern Internal Medicine Conference: difficult-to-treat hypertension. AB - In this article, the author identifies the major causes of difficult-to-treat hypertension and provides guidelines for its management. The data were obtained from multiple clinical series of patients with hypertension resistant to therapy, reports of over-sensitivity to antihypertensive drugs, and the effects of anxiety induced hyperventilation. As many as 15% of patients are resistant to antihypertensive therapy. Of the multiple possible causes for resistance, volume overload is the most common. Volume overload, in turn, is related to multiple factors, with inadequate diuretic therapy playing a major role. Many patients may experience tissue hypoperfusion when given usual doses of antihypertensive therapy, making their hypertension difficult to treat. In the author's experience, an even larger number of patients have psychosomatic symptoms, usually attributable to anxiety-induced hyperventilation, that often are blamed on their therapy. Therefore, hypertension may be difficult to treat for various reasons. When the cause is recognized, appropriate management almost always can be provided. PMID- 7771506 TI - 64th Annual meeting of the American Association of Physical Anthropologists. Oakland, California, March 28-April 1, 1995. Abstracts. PMID- 7771507 TI - Neutral phosphate administration generates and maintains renal metabolic alkalosis and hyperparathyroidism. AB - We examined the effects of chronic intravenous neutral phosphate administration on systemic acid-base equilibrium and parathyroid function in six normal, NaCl replete male human subjects under metabolic balance conditions. The subjects received 4.35 mmol of neutral sodium phosphate.kg body wt-1.day-1 intravenously and continuously for 7 days and the same amount of sodium as NaCl during control and recovery. Blood pH increased from 7.388 to 7.411 (P < 0.001) and plasma bicarbonate from 23.5 to 26.0 mmol/l (P < 0.001). Urinary pH increased from 6.58 to 6.79 (P < 0.001). Net acid excretion increased from 59 to 100 mmol/24 h (P < 0.001). Plasma ionized calcium concentration decreased and plasma phosphate concentration increased transiently. Serum intact parathyroid hormone increased from 24 to 62 pg/ml (P < 0.001). Chronic phosphate administration also resulted in a significant increase in renal phosphate clearance (35 to 229 ml/min) and decrease in the fractional excretion of calcium (1.8 to 0.9%). Thus chronic intravenous phosphate administration generates and maintains renal metabolic alkalosis in salt-replete humans and induces hyperparathyroidism. The severity of metabolic alkalosis is mitigated by an apparent increase in effective endogenous acid production as evidenced by the significant increase in steady-state net acid excretion. PMID- 7771508 TI - Activation of protein kinase C stimulates cAMP phosphodiesterase in rat renal collecting tubule. AB - The present study was undertaken to evaluate whether protein kinase C (PKC) affects adenosine 3',5'-cyclic monophosphate phosphodiesterase (cAMP-PDIE) activity in microdissected rat renal medullary collecting tubules (MCT). Phorbol 12-myristate 13-acetate (PMA, 10(-8) M), an activator of PKC, significantly stimulated cAMP-PDIE activity in intact MCT (29.5 +/- 1.5 to 38.3 +/- 3.7 fmol.min-1.mm-1, P < 0.05) but not in the proximal straight tubule [4.7 +/- 0.8 vs. 4.8 +/- 0.8, not significant (NS)] or the medullary ascending limb of Henle's loop (20.5 +/- 2.1 vs. 22.4 +/- 2.8, NS). PMA-stimulated cAMP-PDIE activity was reversed by PKC inhibitors, staurosporine (10(-8) M) and calphostin C (10(-8) M), but not by the cyclooxygenase inhibitor, indomethacin (5 x 10(-6) M). 1,2 Dioctanoyl-sn-glycerol (50 micrograms/ml), a synthetic analogue of diacylglycerol that stimulates PKC, also increased cAMP-PDIE activity in broken-cell preparations from MCT. This stimulation was also suppressed by staurosporine (10( 8) M) and calphostin C (10(-8) M). The stimulatory effect of PMA on cAMP-PDIE activity was lost with rolipram (10(-4) M), a type IV PDIE inhibitor, whereas it was preserved with N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) (10(-4) M), a calmodulin inhibitor, or vinpocetin (10(-4) M), a direct inhibitor of type I PDIE. From these results, we suggest that activation of PKC specifically stimulates rolipram-sensitive cAMP-PDIE, but not the calmodulin-sensitive isozyme, in rat MCT. PMID- 7771509 TI - Ontogeny of rabbit renal cortical NHE3 and NHE1: effect of glucocorticoids. AB - The neonatal proximal tubule has a lower rate of bicarbonate absorption and Na+/H+ antiporter activity than the proximal tubule of adult animals. Two isoforms of the Na+/H+ antiporter have been localized to the proximal tubule. NHE3 is located on the apical membrane, whereas NHE1, the isoform found on most mammalian cells, is present on the basolateral membrane. The Na+/H+ antiporter isoforms that increase with renal maturation are unknown. The purpose of the present study was to examine the maturation of rabbit renal cortical NHE3 and NHE1 mRNA and protein abundance and to determine whether the rate of maturation of these isoforms was affected by glucocorticoids. Renal cortex from neonatal rabbits (1 wk) had approximately one-fourth the NHE3 mRNA and protein abundance as that from adult animals. Renal cortical NHE1 mRNA and protein abundance did not change significantly during maturation. Glucocorticoids have been shown to accelerate the maturation of neonatal bicarbonate absorption and apical membrane Na+/H+ antiporter activity. Daily subcutaneous administration of dexamethasone starting at 4 days of age (10 micrograms/100 g body wt) for 3 days and 2 h before being killed resulted in a twofold increase in NHE3 mRNA abundance and a threefold increase in NHE3 protein abundance. NHE1 mRNA and protein abundance were unaffected. These data show that there is selective maturation of NHE3 during renal cortical development, which can be accelerated by administration of glucocorticoids. PMID- 7771510 TI - ANG II dependence of tubuloglomerular feedback responsiveness in hypertensive ren 2 transgenic rats. AB - The present study was performed to determine the angiotensin II (ANG II) dependence of stop-flow pressure (SFP) tubuloglomerular feedback responses in hypertensive transgenic rats [strain name: TGR(mRen2)27] harboring the mouse ren 2 renin gene. SFP feedback responses to increases in late proximal perfusion rate were assessed in pentobarbital-anesthetized male ren-2 transgenic rats during control conditions and after administration of the AT1 receptor antagonist, L 158,809 (1 mg/kg iv). During control conditions, increases in late proximal perfusion rate elicited flow-dependent decreases in SFP. The magnitude of the maximal SFP feedback response to a late proximal perfusion rate of 40 nl/min averaged 16.1 +/- 1.4 mmHg (n = 7), a value higher than that normally observed in normotensive rats. Administration of L-158,809 decreased mean arterial blood pressure (174 +/- 6 vs. 117 +/- mmHg, P < 0.01, n = 10) and attenuated the magnitude of the maximal SFP feedback response by 84 +/- 4% (16.1 +/- 1.4 vs. 2.6 +/- 0.5 mmHg, P < 0.01, n = 7). In contrast, mechanical reduction of renal arterial pressure from 179 +/- 5 to 113 +/- 1 mmHg (P < 0.01, n = 7) attenuated the magnitude of the maximal SFP feedback response by only 43 +/- 5% (14.4 +/- 1.9 vs. 7.9 +/- 0.7 mmHg, P < 0.01, n = 7), indicating that approximately one half of the attenuation of SFP feed-back responses elicited by AT1 receptor blockade was due to removal of the stimulatory effect of ANG II on the sensitivity of the tubuloglomerular feedback mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771511 TI - Convergence of apical and basolateral endocytic pathways for beta 2-microglobulin in LLC-PK1 cells. AB - Polarized epithelial cells internalize molecules from both apical and basolateral (BL) plasma membrane (PM) domains via receptor-mediated endocytosis. In the kidney, low-molecular-weight proteins (LMWP) are internalized across the apical membrane of proximal tubule cells and degraded in lysosomes. Although indirect evidence suggests some uptake may occur at the BL surface, in vivo studies performed in rats suggest little if any LMWP uptake occurs at the BL surface. The studies presented here showed that native human beta 2-microglobulin (beta 2M) was internalized across the apical surface and followed the same intracellular pathway in the proximal tubule-derived cell line LLC-PK1 as that described in vivo. Either 125I- or gold-labeled beta 2M (125I-beta 2M and gold-beta 2M) bound specifically and reversibly to the apical surface of confluent LLC-PK1 cells. These results were qualitatively similar to previously documented in vivo results. Subsequently, using gold-beta 2M and LLC-PK1 cells grown on porous supports, we showed that a functional uptake system for the LMWP beta 2M was present at the BL surface. Finally, using different-size gold particles conjugated to beta 2M applied simultaneously to the apical and BL surfaces, we observed that apical and BL endocytic routes converged in multivesicular acid phosphatase-negative endosomal structures. Taken together, these data imply that beta 2M can be internalized across both apical and BL domains and that the two pathways converge at a multivesicular level within the endosomal pathway. PMID- 7771512 TI - Disturbances in renal microcirculation induced by myoglobin and hemorrhagic hypotension in anesthetized rat. AB - The question was studied of whether myoglobin (Mb), when released into the general circulation during hemorrhagic hypotension (HH), causes disturbances of renal blood flow. In anesthetized rats 250 mg/kg Mb was intravenously infused within 1 h; HH at 50 mmHg with subsequent retransfusion was induced for 30 min. By allowing two dyes to circulate for 1 and 3 min, respectively, and detecting their localization histologically after rapid freezing of the organ, intrarenal distribution of capillary blood flow was studied. In contrast to the results obtained with Mb or HH alone, when Mb was infused during HH, the development of large areas within cortex and medulla lacking any capillary perfusion was observed. In > 70% of the tissue, a distance > 60 microns to the next dye-labeled capillary was found (in controls 0%). At this time total renal flow had decreased from 5.3 to 0.20 ml/min (HH without Mb: 5.1 to 1.1 ml/min). It is concluded that the observed changes in renal blood flow contribute to the known direct nephrotoxic potential of Mb. PMID- 7771513 TI - Heterogeneity of chloride/base exchange in rabbit superficial and juxtamedullary proximal convoluted tubules. AB - Active transcellular NaCl transport in the proximal convoluted tubule (PCT) is via apical parallel Na/H and Cl/base exchange. The mechanism of Cl/base exchange remains unclear. The present in vitro microperfusion study examined the mechanism of Cl/base exchange in superficial and juxtamedullary PCT by examining the rate of change in intracellular pH in response to luminal Cl removal. In superficial PCT the rate of Cl/base exchange was 24.0 +/- 2.3 without formate, 36.4 +/- 6.6 with 10 microM formate (P < 0.05), and 43.6 +/- 2.8 pmol.mm-1.min-1 (P < 0.001) with 1 mM luminal formate. Cl/base exchange was inhibited by luminal 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in the presence and absence of formate. In juxtamedullary PCT, Cl/base exchange was 22.2 +/- 3.8 without formate and 25.0 +/- 5.4 pmol.mm-1.min-1 in the presence of 1 mM luminal formate [P = not significant (NS)]. Cl/base exchange was inhibited by luminal DIDS in juxtamedullary PCT. The rates of Cl/base exchange in both superficial and juxtamedullary PCT were not affected by 0.1 mM acetazolamide and 2 mM cyanide and were the same in the presence and absence of HCO3/CO2, consistent with Cl/OH rather than Cl/HCO3 exchange. To examine the effect of formate on PCT transport, tubules were perfused with a high-Cl solution without organics simulating late proximal tubular fluid. In superficial PCT net volume absorption (JV) was 0.00 +/ 0.05 in the absence of formate and 0.14 +/- 0.06 nl.mm-1.min-1 in the presence of 1 mM formate (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771514 TI - Vasopressin and cAMP stimulate electrogenic chloride secretion in an IMCD cell line. AB - Previously, we demonstrated that the mIMCD-K2 cell line, derived from the inner medullary collecting duct (IMCD) of a transgenic mouse, secretes Cl- by an electrogenic mechanism [N. L. Kizer, B. Lewis, and B. A. Stanton, Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995]. The objective of the present study was to characterize the cellular mechanisms of electrogenic Cl- secretion (IscCl) and to determine whether arginine vasopressin (AVP) and adenosine 3',5'-cyclic monophosphate (cAMP) stimulate IscCl. To this end, we measured IscCl across monolayers of mIMCD-K2 cells mounted in Ussing-type chambers. AVP increased IscCl with a Michaelis constant (Km) of 2.1 +/- 0.7 x 10( 12) M. 1-Desamino-8-D-AVP, a specific V2 receptor agonist, increased IscCl from 3.3 +/- 0.4 to 17.4 +/- 1.3 microA/cm2, 8-(4-Chlorophenylthio)-cAMP, a cell permanent analogue of cAMP, a second messenger of AVP, increased IscCl from 1.4 +/- 0.3 to 15.2 +/- 1.2 microA/cm2. Furosemide and bumetanide, inhibitors of Na(+)-2Cl(-)-K+ cotransport, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl-/HCO3- exchange, reduced IscCl when added to the basolateral solution. Our data suggest that AVP, via V2 receptors, and the second messenger cAMP stimulate IscCl and that Cl- secretion by mIMCD-K2 cells involves uptake of Cl- across the basolateral membrane by Na(+)-2Cl(-)-K+ cotransport and Cl-/HCO3- exchange and diffusion out of the cells across the apical membrane by cystic fibrosis transmembrane conductance regulator Cl- channels. PMID- 7771515 TI - Glucocorticoid upregulates Na-K-ATPase alpha- and beta-mRNA via an indirect mechanism in proximal tubule cell primary cultures. AB - Adrenalectomy leads to the decline in the levels of renal Na-K adenosinetriphosphatase (Na-K-ATPase) alpha- and beta-subunit protein and mRNA. Both alpha- and beta-mRNA, however, return to the control level within 1 h after corticosterone administration. Whether or not glucocorticoid acts directly on a specific segment of nephron to upregulate Na-K-ATPase has not been determined. Studies were undertaken in an attempt to elucidate this problem. Using primary cultures of renal proximal tubules, we found that 24-h treatment with dexamethasone augmented Na-K-ATPase activity and induced coordinate increase of alpha- and beta-protein and mRNA abundance dependent on the doses in the range of 10(-8) to 10(-6) M. We further demonstrated that 24-h incubation of dexamethasone (10(-7) M) enhanced Na-K-ATPase activity by 58 +/- 14%, alpha- and beta-protein abundance by 70 +/- 18 and 51 +/- 10%, and alpha- and beta-mRNA levels by 87 +/- 12 and 62 +/- 11%, respectively. The time course studies revealed that significant increase of Na-K-ATPase activity and alpha and beta-protein abundance was reached within 4 hr of dexamethasone treatment. Pretreatment of cultured proximal tubule cells with cycloheximide (20 micrograms/ml) completely inhibited dexamethasone-induced increase of Na-K-ATPase alpha- and beta-mRNA. Our results indicate that dexamethasone upregulates Na-K-ATPase in proximal tubule cells via pretranslational mechanisms, which may be mediated by proteins. PMID- 7771516 TI - Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production. AB - Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure. PMID- 7771517 TI - Calcium activation mechanisms in the renal microvascular response to extracellular ATP. AB - Previous studies have suggested a paracrine role for extracellular ATP in the regulation of afferent arteriolar tone. The current study was conducted to determine the dependence of this response on calcium entry mechanisms. Experiments were performed in vitro using the blood-perfused juxtamedullary nephron technique combined with video microscopy. The afferent arteriolar response to alpha, beta-methylene ATP was determined before and after treatment with the calcium channel blockers, diltiazem or felodipine. alpha, beta-Methylene ATP was used to obviate concerns over responses being elicited by ATP or by ATP hydrolysis products such as adenosine. Previous studies have shown that afferent arteriolar responses to alpha, beta-methylene ATP are comparable to those elicited by ATP. alpha, beta-Methylene ATP (1.0 microM) induced a rapid initial afferent vasoconstriction of 72.5 +/- 10.6%, which partially recovered to a stable diameter 11.3 +/- 1.7% smaller than control (P < 0.01 vs control). Afferent diameter returned to control diameter on removal of ATP from the bath. Diltiazem or felodipine treatment significantly increased afferent diameter by 5.6 +/- 2.3 and 16.4 +/- 4.6%, respectively (P < 0.05). In the presence of either diltiazem or felodipine, the initial vasoconstriction to alpha, beta-methylene ATP was attenuated, and the sustained vasoconstriction was completely blocked. Removal of calcium from the extracellular medium completely abolished both the initial and sustained vasoconstrictor response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771518 TI - Restoration of vasa recta hemodynamics and pressure natriuresis in SHR by L arginine. AB - An increase in medullary blood flow has been implicated as a mediator of the natriuresis following increases in renal perfusion pressure (RPP). We examined whether administration of L-arginine, the substrate for nitric oxide production, restores the impaired vasa recta hemodynamic response to increases in RPP and the blunted pressure natriuresis of the spontaneously hypertensive rat (SHR). The response of descending (QDVR) and ascending vasa recta blood flow (QAVR) and of urinary sodium excretion (UNaV) was examined as RPP was increased by means of an adjustable aortic clamp placed above the renal arteries in young SHR and Wistar Kyoto (WKY) rats. When RPP was increased in SHR receiving infusion of L-arginine (n = 7), QDVR and QAVR increased significantly in association with increases in UNaV. In SHR receiving the inactive enantiomer, D-arginine (n = 7), similar increases in RPP failed to increase QAVR and QDVR and were associated with an attenuated increase in UNaV. WKY animals infused with either D-arginine or L arginine had increases in QDVR, QAVR, and UNaV in response to increases in RPP that were of similar magnitude to SHR receiving L-arginine. Thus the administration of L-arginine to SHR restores the pressure-dependent increases in renal medullary hemodynamics in association with restoration of pressure natriuresis. PMID- 7771519 TI - Glomerular handling of circulating glycated albumin in the normal mouse kidney. AB - In the present study, we have evaluated the glomerular handling of circulating glycated albumin in the normal mouse kidney by quantitative immunocytochemistry. Bovine serum albumin (BSA) was glycated in vitro and dinitrophenylated. Glycated and nonglycated probes were introduced into the circulation of anesthetized mice and traced by postembedding immunogold cytochemistry after 10 and 30 min of circulation. Endogenous albumin, as well as dinitrophenylated native BSA (DNP BSA) and glycated albumins (DNP-gBSA), were localized within the capillary lumen, glomerular and peritubular basement membranes, and the mesangial matrix. Morphometric evaluation of the labeling over the glomerular basement membrane (GBM) revealed a peak of labeling in the endothelial side for either endogenous albumin or DNP-BSA. In contrast, the labeling distribution for DNP-gBSA showed a shift toward the epithelial side, suggesting a further penetration of the glycated probe into the GBM. When coinjected with gBSA, DNP-BSA was found to display a labeling distribution similar to that displayed by DNP-gBSA. These results indicate that the glycated tracer penetrates the normal glomerular wall deeper than the nonglycated one. Moreover, glycated albumin increases the infiltration of the nonglycated tracer through the normal glomerular wall. Circulating glycated serum proteins thus appear to play an important role in the onset of the glomerular dysfunction and proteinuria, which take place in long term hyperglycemic states. PMID- 7771520 TI - Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland. AB - The angiotensin II (ANG II) receptors have been pharmacologically classified into two major distinct types, designated AT1 and AT2. A high transient expression of AT2 receptors in the fetal tissues has been previously demonstrated. This study describes the cellular distribution of AT2 receptor mRNA in the developing rat kidney and adrenal gland by in situ hybridization with 35S-labeled cRNA probes. From day 12 of fetal life (F12) to day 15 postpartum (D15) AT2 mRNA was detected in the undifferentiated nephrogenic mesenchymal tissue but not in the immature and mature glomeruli and tubules of the kidney. No AT2 mRNA was observed in the kidney after D22. The adrenal gland also expressed AT2 receptor mRNA early during development from F12 but, unlike the kidney, continuously expressed the mRNA at high levels through to adulthood. The disappearance of AT2 mRNA in the kidney was synchronous with the completion of nephrogenesis and suggests that ANG II might act through this receptor as a differentiation/growth factor during nephron development. In the adrenal gland ANG II could act as a hormone and also as a differentiation/growth factor via the AT2 receptor. PMID- 7771521 TI - 5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis. AB - We examined the mechanism by which the cytochrome P-450 metabolite of arachidonate, 5,6-epoxyeicosatrienoic acid (5,6-EET), modulates electrogenic transport in the rabbit cortical collecting duct (CCD). 5,6-EET depolarized transepithelial voltage (VT) in a concentration-dependent manner with a maximal effect at 1 microM. None of the other EET regioisomers (8,9-, 11,12-, or 14,15 EET; all at 1 microM) affected VT, This action was also stereoselective, with 5(S),6(R)-EET producing a 2.5-fold greater effect on VT than 5(R),6(S)-EET (1 microM each). Like basolateral prostaglandin E2 (PGE2), both luminal and basolateral 5,6-EET increased cytosolic Ca2+ concentration ([Ca2+]i) in the rabbit CCD. Pretreatment with cyclooxygenase inhibitors (10 microM ibuprofen or 5 microM indomethacin) completely blocked both the [Ca2+]i increase and the change in VT. Neither 5,6-epoxy-PGE1 nor 5-hydroxy-PGI1, cyclooxygenase metabolites of 5,6-EET, affected VT. However, when added to primary cultures of rabbit CCDs, 5,6 EET stimulated endogenous PGE2 synthesis. We propose that 5,6-EET stimulates endogenous prostaglandin synthesis, which inhibits electrogenic ion transport in the CCD. PMID- 7771522 TI - ANG II is a mitogen for a murine cell line isolated from medullary thick ascending limb of Henle's loop. AB - A murine SV40-transformed renal epithelial cell line derived from medullary thick ascending limb of Henle's loop (MTAL) was established and characterized by morphology, antigen expression, and biochemical criteria. These MTAL cells express a single class of high-affinity receptors for angiotensin II (ANG II) and transcripts for the AT1 subtype of ANG II receptors. ANG II, in a dose-dependent manner, induced proliferation of MTAL cells. This observation is in striking contrast to syngeneic proximal tubular cells in which it was previously shown that the peptide induced cellular hypertrophy and slightly inhibited proliferation [G. Wolf and E. G. Neilson. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28: F768-F777, 1990]. The AT1-receptor antagonist losartan (10(-6) M), but not an AT2-receptor antagonist, blocked the mitogenic effects of ANG II in MTAL cells. Coincubation of quiescent MTAL cells with ANG II and 5% fetal calf serum further increased proliferation compared with cells grown only in serum. In contrast to proximal tubular cells, ANG II failed to induce transforming growth factor-beta 1 mRNA and protein synthesis in MTAL cells. Our data collectively suggest that ANG II is a mitogen for MTAL cells in vitro. Therefore, epithelial cells derived from different parts of the nephron, even when transformed with SV40 virus and while under cell culture conditions, exhibit a distinct pattern of growth behavior after stimulation with ANG II. PMID- 7771524 TI - Effect of nitric oxide on renin secretion. II. Studies in the perfused juxtaglomerular apparatus. AB - To examine the possible role of NO in macula densa control of renin secretion, we examined the effects of varying NO availability on renin release in the isolated perfused rabbit juxtaglomerular apparatus (JGA). Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in renin secretion from (as log of nano-Goldblatt hog units vs. time, i.e., log nGU/min) 1.09 +/- 0.34 to 0.46 +/- 0.24 log nGU/min, with the greatest change occurring at the first concentration step. The presence of 0.7 mM N omega-nitro-L-arginine (NNA), an NO synthase inhibitor, in the luminal fluid significantly reduced renin secretion at the lowest Na/Cl concentration ratio to 0.65 +/- 0.32 log nGU/min (P < 0.01 compared with control). Renin secretion at the higher Na/Cl concentration ratios was not significantly affected by NNA compared with control. In contrast to these results, the addition of the NO donor nitroprusside (1 mM) to the bath caused a reduction in renin secretion from 1.0 +/- 0.39 to 0.47 +/- 0.46 log nGU/min (P < 0.05), an effect that was reversed by bath addition of 0.01 mM methylene blue. Similarly, addition of L-arginine (0.7 mM) to the bath reduced renin secretion from 0.99 +/- 0.37 to 0.81 +/- 0.38 log nGU/min (P < 0.01), whereas addition of L-arginine to the luminal fluid increased renin secretion from 0.85 +/- 0.43 to 1.94 +/- 0.46 log nGU/min (P < 0.05). The stimulatory effect of luminal L-arginine was reversed by the luminal addition of NNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771523 TI - Effect of nitric oxide on renin secretion. I. Studies in isolated juxtaglomerular granular cells. AB - Experiments were performed on juxtaglomerular granular cells (JGC) in short-term primary culture to determine the direct immediate effect of NO on renin secretion and to test whether JGC are able to generate NO. Renin secretion was measured repeatedly over short time intervals in a cell superfusion system. Renin release did not significantly decrease over a 40-min observation period in untreated JGC. Addition of sodium nitroprusside (SNP) caused a reduction in renin release (measured in nano-Goldblatt hog units vs. time, i.e., nGU/min) from 479 +/- 25, 423 +/- 70, and 388 +/- 54 nGU/min to 295 +/- 19 (n = 5), 102 +/- 21 (n = 7), and 71 +/- 9 nGU/min (n = 6) with 10(-5), 10(-4), and 10(-3) M SNP, respectively. In the presence of the guanylate cyclase inhibitor methylene blue at 10(-4) M, SNP at 10(-4) M had no significant effect on renin secretion. 8-Bromoguanosine 3',5' cyclic monophosphate at 10(-4) M in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-3) M) caused a reduction of renin secretion to 50.1 +/- 3.6% of control. To examine the possibility that renin secretion is affected by NO release from JGC, we assessed the effect of the NO synthase (NOS) substrate L-arginine (10(-3) M) and the NOS blocker N omega-nitro L-arginine (10(-4) M) on renin secretion. Renin release was not significantly altered by either stimulation or inhibition of NOS activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771525 TI - Effects of barium ions on tubuloglomerular feedback. AB - The furosemide sensitivity of the tubuloglomerular feedback (TGF) response has suggested an important role for the Na-2Cl-K cotransporter in the mechanism by which increased luminal NaCl concentration causes afferent arteriolar vasoconstriction. The present experiments in anesthetized rats were performed to evaluate the effect of K channel blockade with Ba on TGF, since Ba has been shown to inhibit NaCl transport in the thick ascending limb. The presence of either 1.5 or 2 mM BaCl2 during retrograde perfusion with a 135 mM NaCl solution reduced the decrease of early proximal flow rate (VEP) by 2.7 +/- 0.76 (P < 0.02) and 4.2 +/- 0.8 nl/min (P < 0.01) compared with perfusion without BaCl2. Retrograde perfusion with 38 mM NaCl + 5 mM KCl reduced VEP by 10.4 +/- 1.3 nl/min, whereas 40 mM NaCl + 1.5 mM BaCl2 caused a reduction by only 6.1 +/- 1.4 nl/min (P < 0.001). In contrast to the inhibition caused by retrograde perfusion with low concentrations of BaCl2, increased vasoconstriction was seen during retrograde perfusion with 5 mM BaCl2 or during orthograde perfusion with 10 mM BaCl2. The addition of 10(-4) M furosemide to a solution containing 5 mM BaCl2 largely blocked the increased vasoconstrictor response. Peritubular perfusion with a solution containing 5 mM BaCl2 caused a fall in stop-flow pressure in an adjacent nephron by 10.7 +/- 1.5 mmHg (P < 0.001). These results indicate that under our experimental conditions Ba ions exert a dual effect on vascular responses to changes in luminal NaCl concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771527 TI - Capillary network structure does not affect theoretical analysis of glomerular size selectivity. AB - Anatomical studies have demonstrated that the glomerular capillaries are complex and heterogeneous networks. Conventional models of glomerular size selectivity, however, are based on the assumption of simplified geometries. We developed a theoretical model of glomerular size-selective function based on the geometric data obtained in a previous reconstruction of a glomerular network from a normal Munich-Wistar rat. This heterogeneous model was compared with the homogeneous model conventionally used to calculate membrane selective parameters from the fractional clearance of two test solutes, neutral dextran and Ficoll. For both models we assumed a hypothetical log-normal distribution of pore sizes and calculated optimal membrane pore-size parameters using previously published values of fractional clearances. The difference between the sieving coefficients calculated with the two models was negligible, never exceeding 5.5%. Since the homogeneous model does not consider the pressure drop along the glomerular capillary, we also computed fractional clearances with the homogeneous model, assuming the same pressure drop as in the heterogeneous one. The differences in computed fractional clearances using the homogeneous model with and without a pressure drop were less than 1.2%. We concluded that models based on identical capillary networks can therefore be used for interpreting sieving coefficients for macromolecules. PMID- 7771526 TI - A novel method for infusing drugs continuously into the renal artery of rats. AB - A method is described to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The device for intrarenal infusion consisted of a multiple-catheter system with a cannula inserted into the renal artery, which was connected to different lines for drug infusions and to one line for oscillating blood back and forth in the renal cannula with a magnetic membrane pump. The blood oscillation served to mix the drugs with renal arterial blood. To verify the usefulness of this procedure, Lissamine green was infused into the renal artery; without the mixing pump the dye was located on a small portion of the kidney surface, whereas the dye could be visualized evenly distributed and less concentrated over the entire kidney with the pump. With the mixing device, intrarenal infusion of angiotensin II, 5 pmol.kg-1.min-1, or norepinephrine, 150 pmol.kg-1.min-1, reduced renal blood flow by approximately 25% without affecting blood pressure. Tenfold higher doses given intravenously had comparable renal effects, but these increased systemic pressure. Without the mixing pump, vasoactive drugs given into the renal artery had a distinctly smaller effect on renal blood flow than with the pump (angiotensin II, 39%; norepinephrine, 49%; and acetylcholine, at 5 nmol.kg-1.min 1, 33%). The results show that intrarenally infused drugs, without a mixing device, have access to an unpredictably small kidney volume, and estimation of their effects on kidney functions can be equivocal. The present device ensures an adequate mixing of drugs with renal blood. PMID- 7771528 TI - Viscoelastic behavior of "in situ" aortic wall during hemorrhagic hypotension. AB - Viscoelastic and electrophysiological mechanisms have been implicated in resetting of baroreceptors in hypertension, but resetting in response to hypotension has been less exhaustively studied. To assess the importance of viscoelastic mechanisms in hypotension, we examined the behavior of the "in situ" aorta during hemorrhage. Fifteen minutes of hemorrhage in anesthetized Wistar rats produced stable hypotension (30 mmHg) and a progressive contraction of the mean aortic caliber (-93.8 +/- 18.0 microns, P < 0.05) compared with control measurements. Contraction was not altered by sinoaortic denervation, vagotomy, nephrectomy, adrenalectomy, hexamethonium (30 mg/kg), losartan (10 mg/kg), V1 antagonist (10 micrograms/kg), arterial pH and blood gas control, or indomethacin (3.0 mg/kg). Aortic contraction was greater in rats treated with N omega-nitro-L arginine (-164.0 +/- 43.0 microns, P < 0.05) than in those treated with sodium nitroprusside (-54.1 +/- 7.5 microns, P < 0.05). The results indicate that aortic contraction is compatible with viscoelastic contraction and suggest that shortening of viscoelastic elements in series with baroreceptor endings increases stress at the baroreceptor membrane and contributes to the development of baroreceptor resetting to hypotension. PMID- 7771529 TI - Unaltered size of right ventricular infarct in dogs with right ventricular hypertrophy induced by pressure overload. AB - We investigated whether right ventricular infarct size is increased in the hypertrophied right ventricle. In dogs, we produced chronic pressure overload induced right ventricular hypertrophy (RVH) and acute pulmonary stenosis (APS) with a similar right ventricular systolic pressure to RVH. Then, in an open-chest model, right coronary artery occlusion for 4 h followed by 1 h of reperfusion was performed in animals with RVH or APS or in controls. Regional myocardial blood flow was measured with nonradioactive colored microspheres. Compared with the control group, regional myocardial oxygen consumption in the right ventricle was increased in the APS but not in the RVH group. The risk area and collateral blood flow were comparable in the three groups. However, the infarct size relative to risk area was increased in the APS group (42.3 +/- 4.9%), but that in the RVH group (21.1 +/- 4.4%) was not different from controls (26.1 +/- 4.2%). Thus right ventricular infarction in the heart with RVH was not increased compared with the normal heart. PMID- 7771530 TI - Impaired subendocardial function in tachycardia-induced cardiac failure. AB - Chronic rapid ventricular pacing (CRVP) in many experimental models induces ventricular dilatation, reduced ejection fraction, and symptomatic congestive heart failure. We have investigated transmural mechanical function in the left ventricular (LV) wall of five Hanford miniature swine before and after CRVP induced failure. Three columns of radiopaque markers 1 mm in diameter were implanted in the anterior LV wall through a median sternotomy. A pair of LV pacing wires were sutured into the myocardium, a pneumatic cuff was placed around the inferior vena cava (IVC), and two fluid-filled Silastic catheters were implanted into the LV apex. Two weeks after surgery, the pigs were suspended awake in a sling, and markers were tracked with biplane cineradiography. The hearts were paced for 3 wk (225-240 beats/min), and the study was repeated with the pacemaker off. Saline infusion and IVC occlusion were used to vary LV end diastolic pressure (EDP) so control-to-failure comparisons could be made at matched LV EDPs. End-systolic strains in the circumferential (E11), longitudinal (E22), and transmural (E33) directions were quantified using finite element methods. There was a significant reduction in E11 and E33 for the subendocardium: in E11, from -0.27 to -0.18; in E33, from 0.83 to 0.46. There were no significant changes in subendocardial E22 or in any of the outer wall normal strains. These results indicate that CRVP causes substantial reduction of subendocardial, but not subepicardial, function; taken together with previous data indicating subendocardial hypoperfusion, these results support the contention that an imbalance between blood flow and oxygen demand plays a role in the etiology of heart failure in this model. PMID- 7771531 TI - Calcium- and sodium-dependent modulation of stretch-induced arrhythmias in isolated canine ventricles. AB - Gadolinium-sensitive stretch-activated channels have been implicated in the process of mechanotransduction signaling of ventricular myocardium. Such channels nonspecifically transport Na+ and Ca2+ in the inward direction. We tested the hypothesis that Na+ and Ca2+ influx are important in the genesis of stretch induced arrhythmias (SIAs) in an isolated, blood-perfused canine ventricle. To elicit SIAs, left ventricular volume was transiently increased in early diastole using a computerized servo-pump system. Monophasic action potential recordings revealed stretch-induced depolarizations (SIDs) that preceded the arrhythmias. In five ventricles, raising the perfusate Ca2+ concentration from 1 to 3 mM increased ventricular sensitivity to SIAs, manifested by a decrease in the volume change required to precipitate an arrhythmia 50% of the time (delta V50) from 19.5 +/- 2.7 to 15.2 +/- 1.9 ml (P < 0.05). When the perfusate Na+ concentration was decreased from 150 to 90 mM in seven ventricles, delta V50 greatly increased (31.1 +/- 14.4 vs. 17.7 +/- 5.3 ml, P < 0.05), and SID amplitude decreased by 47% (P = 0.002). The suppression of SIAs with low extracellular Na+ is unlikely to be mediated by voltage-gated Na+ channels because lidocaine (5 mg/dl) did not alter SID amplitude. Thus the transsarcolemmal Na+ gradient (and probably that of Ca2+) modulates the amplitude of SIDs, which, in turn, initiate SIAs. These data provide initial evidence that Na+ and Ca2+ help mediate the mechanotransduction processes that underly the genesis of SIAs. PMID- 7771532 TI - Vascular compliance and mean circulatory filling pressure in trout: effects of ACE inhibition. AB - Mean circulatory filling pressure (MCFP), whole body vascular compliance (C), and unstressed blood volume (USV) are important indexes of cardiovascular function in mammals, but they have not been measured in fish. In the present experiments, dorsal aortic (PDA) and sinus venosus (PSV) pressures were measured in unanesthetized trout before and during electrical cardiac fibrillation, while blood volume (BV) was manipulated between 50 and 150% of normal. Measurements were repeated after angiotensin-converting enzyme (ACE) inhibition with lisinopril. Cardiac fibrillation (zero-flow condition) rapidly (approximately 5 s) dropped PDA and increased PSV (equals MCFP). MCFP in normovolemic trout (4.8 +/- 0.3 mmHg) varied directly with BV. C determined from in vivo capacitance curves was similar to that obtained gravimetrically, in vitro (3.4 and 3.5 ml.mmHg-1.kg body wt-1, respectively). USV was 13.3 ml/kg body wt (approximately 45% of BV). ACE inhibition reduced PDA in unfibrillated trout at all BV and reduced PDA in fibrillated fish at BV > or = 80%. ACE inhibition did not affect PSV, MCFP, C, or USV. The systemic arteriovenous pressure gradient at zero flow (delta PF0) was greatest at 100% BV (8.2 +/- 0.5 mmHg) and was reduced by ACE inhibition at 80-120% BV. These results show that key indexes of venous function are readily measured in fish and that the trout venous system is not an effector of angiotensin-mediated regulation of arterial blood pressure. Thus angiotensin acts solely on arterial resistance vessels. Furthermore, the drop in delta PF0 during ACE inhibition is due to a decrease in arteriolar resistance. PMID- 7771533 TI - Effects of inotropic stimulation on energy metabolism and systolic function of ischemic right ventricle. AB - This study determined whether dobutamine enhances regional systolic function in the ischemic right ventricle (RV) at the cost of adverse effects on regional energy metabolism. Seventeen alpha-chloralose-anesthetized, open-chest pigs were studied under four conditions: 1) control; 2) dobutamine infusion (mean dose 9 micrograms.kg-1.min-1); 3) RV ischemia (45 +/- 5% reduction in RV free wall blood flow for 100 min); and 4) continued ischemia with dobutamine. Regional RV free wall high-energy phosphate metabolites were measured by 31P nuclear magnetic resonance (NMR) spectroscopy or by high-speed drill biopsies of the RV free wall. Regional RV free wall substrate and O2 consumption were measured using coronary venous blood sampling. Global RV systolic function was assessed by the maximal first derivative of RV pressure (dP/dtmax), and regional RV free wall systolic function was assessed by systolic segment shortening in the ischemic zone. Right coronary artery constriction caused markedly depressed regional RV systolic function, net lactate production, and coronary venous acidosis. Surprisingly, high-energy phosphates were unchanged compared with control. Addition of dobutamine caused a further decline in coronary venous pH and continued lactate production but did not reduce high-energy phosphates. While dobutamine markedly enhanced global RV systolic function (RV dP/dtmax 201 +/- 19% of control), systolic shortening in the ischemic RV free wall remained severely depressed (47 +/- 18% of control) despite dobutamine. The mechanism of high-energy phosphate preservation is likely due to diminished consumption of ATP in the hypocontractile ischemic region. PMID- 7771535 TI - Thyroid status and Na(+)-K+ pump current, intracellular sodium, and action potential duration in rabbit heart. AB - Thyroid status influences the abundance of Na(+)-K+ pumps in the heart. To evaluate whether this phenomenon may contribute to a dependence of the action potential duration (APD) on thyroid status, we induced hypothyroidism in a group of New Zealand White rabbits. Another group was treated similarly but also received triiodothyronine (T3). Right ventricular myocytes were isolated and voltage clamped at -40 mV. We identified Na(+)-K+ pump current (Ipump) as a ouabain-induced shift in holding current. Mean Ipump, measured using patch pipettes containing 10 mM Na+, was 0.24 +/- 0.02 pA/pF in 9 cells from 4 hypothyroid rabbits and 0.48 +/- 0.05 in 10 cells from 4 rabbits treated with T3 (P < 0.001). Because thyroid status influences Na+ influx, we measured intracellular Na+ activity (aiNa) in right ventricular papillary muscles. We found that aiNa was 5.20 +/- 0.42 mM in nine papillary muscles from seven hypothyroid rabbits and 7.62 +/- 0.69 mM in nine papillary muscles from six rabbits treated with T3 (P < 0.01). The effect of thyroid-induced changes in Ipump and aiNa on APD was stimulated with a computer model. The simulations predicted that thyroid-induced changes in Ipump can influence APD. The predicted changes were similar to changes in APD measured in isolated papillary muscles. PMID- 7771534 TI - Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis. AB - This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET-1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-1. Acute volume expansion (+17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-1 (+129%) and a decrease (-99%) in the urinary excretion of ET-1. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-1. Passive elevation of an arm resulting in a local decrease of venous blood pressure (-17 mmHg) elicited an increase of the local formation of ET-1, with a 10-fold increase in the venous arterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-1 was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin-generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-1 appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume. PMID- 7771536 TI - Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs. AB - The present study explored the effects of a potent antioxidant, the 21 aminosteroid U-74006F, on the systemic and regional hemodynamics and the oxygen extraction capabilities during endotoxic shock. Twenty-four anesthetized dogs were randomized into three groups. Group 1 (n = 8) served as control. Group 2 (n = 8) and group 3 (n = 8) received 2 mg/kg iv of Escherichia coli endotoxin, followed 30 min later by saline infusion. Group 3 was given U-74006F as an intravenous bolus of 80 micrograms/kg followed by an infusion of 10 micrograms.kg 1.min-1, and group 2 received an equivalent volume of vehicle. Tamponade was induced 30 min later to study the oxygen extraction capabilities of the animals. Compared with the endotoxin-alone group, the U-74006F-treated dogs maintained higher mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index and lower pulmonary vascular resistance. They also showed a higher fractional blood flow to mesenteric and renal beds. Endotoxin administration increased whole body critical oxygen delivery (DO2crit) from 7.7 +/- 2.4 to 12.0 +/- 1.9 ml.kg-1.min-1 (P < 0.05), but U-74006F decreased DO2crit to 7.8 +/- 2.0 ml.kg-1.min-1 (P < 0.05 vs. endotoxin alone). Endotoxin decreased critical oxygen extraction ratio (O2ERcrit) from 75.0 +/- 12.7 to 44.3 +/- 8.7% (P < 0.05), but U-74006F increased O2ERcrit to 64.1 +/- 11.2% (P < 0.05 vs. endotoxin alone). U-74006F also decreased endotoxin-induced elevation of mesenteric and renal DO2crit and markedly increased regional O2ERcrit. Systemic and regional blood lactate concentrations were lower in the U-74006F-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771538 TI - ANP secretion from small cell lung cancer cell lines: a potential model of ANP release. AB - Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of approximately 10(-20) g.cell-1.min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99 126) and ANP-(1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771537 TI - Adenosine-induced vasodilation: receptor characterization in pulmonary circulation. AB - Adenosine mediates vascular smooth muscle relaxation in the pulmonary circulation. The A2 receptor has been suggested to mediate adenosine-induced vasodilation (AIV). In this study, the effect(s) of selective adenosine agonist and antagonist on the hypoxic pressor response (HPR) was assessed in the isolated blood-perfused rat lung. Adenosine (0.075-7.5 mM) infusion (0.125 ml/min) into the pulmonary artery dose dependently attenuated the HPR. AIV was mimicked by 10 microM 5'-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist. Adenosine- and NECA-induced vasodilation were attenuated by 67 microM 8-(p sulfophenyl)theophylline. In contrast, NECA-induced vasodilation was not attenuated by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 microM). At 10 microM, a minimal vasodilatory effect was seen with the nonselective adenosine agonists CV-1808 and N6-(2-phenylisopropyl)adenosine (R-PIA) compared with NECA. The highly selective A2a agonist 2-[p-(2-carboxyethyl)phenyl amino]-5'-N-ethyl carboxamido adenosine (CGS-21680C, 10 microM) and A1 agonist 2-chloro-N6 cyclopentyladenosine (CCPA, 10 microM) had no vasodilatory effect. Neither the K+ channel blockers tetraethylammonium chloride (10 mM) and glibenclamide (100 microM) nor the NO synthase inhibitor N omega-nitro-L-arginine methyl ester attenuated NECA-induced vasodilation. These findings suggest that AIV is mediated via the A2b receptor and that AIV occurs via an NO-independent mechanism. PMID- 7771540 TI - Indirect stimulation of Ca(2+)-activated Cl- current by Na+/Ca2+ exchange in rabbit portal vein smooth muscle. AB - Macroscopic currents were recorded in freshly dissociated smooth muscle cells from the rabbit portal vein using the tight seal whole cell recording mode (22 degrees C). In some experiments, the indo 1 fluorescence technique was used to simultaneously monitor the changes in the concentration of free intracellular Ca2+ ([Ca2+]i; indo 1 ratio, 400/500 nm). In cells exposed to tetraethylammonium chloride (TEA) to inhibit K+ channels and 1-10 microM nifedipine or nicardipine to inhibit L-type Ca2+ channels, cell dialysis with 30 mM Na+ increased [Ca2+]i and induced membrane current consistent with the activation of Ca(2+)-activated Cl- channels [ICl(Ca)]. From holding potential (HP) of -60 mV, high intracellular Na+ concentration ([Na+]i)-mediated current was instantaneous in response to 0.5- to 10-s voltage clamp pulses from -80 to +20 mV; steps ranging from +20 to +80 mV evoked slow time-dependent outward current (I(t); superimposed on the instantaneous current) and voltage-dependent Ca2+ transient; on return to HP, slow inward tail current appeared that reflected deactivation of I(t). Both current components 1) exhibited outward rectifying properties, 2) reversed near the predicted equilibrium potential for Cl-, 3) were stimulated by elevation of extracellular Ca2+ concentration, 4) were abolished when the cells were dialyzed with 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and 5) were inhibited by extracellular application of niflumic acid (50 microM). Complete replacement of extracellular Na+ concentration with tetramethylammonium increased both the instantaneous and time-dependent components of ICl(Ca), resting [Ca2+]i at -60 mV and Ca2+ transient at +40 mV. Cell dialysis with Na(+) free pipette solution prevented these effects. Our results are consistent with an indirect mechanism of stimulation of ICl(Ca), which involves intracellular Ca2+ accumulation via reverse-mode electrogenic Na+/Ca2+ exchange activity. PMID- 7771539 TI - Transmural bioenergetic responses of normal myocardium to high workstates. AB - The response of myocardial high-energy and inorganic phosphates (HEP and Pi, respectively) and associated changes in myocardial blood flow, lactate uptake, and O2 consumption (MVo2) rates were examined in an open-chest canine model during progressively increasing workloads achieved by catecholamine infusion. HEP and Pi levels (measured with transmurally localized 31P-nuclear magnetic resonance spectroscopy) were unaffected by moderate increases in the level of energy expenditure but were significantly altered by high workloads, especially in the subepicardium. The MVo2 and HEP data from three different protocols that utilized pharmacological augmentation of blood flow demonstrated that the maximal rate of myocardial energy production during inotropic stimulation was dictated by perfusion limitation. This limitation was more severe in the subepicardial layer at the high workloads despite equivalent or even higher increases in blood flow to this layer, reflecting a preferential enhancement of demand in the outer layer by catecholamines. In contrast, under basal conditions, existence of a marginal perfusion limitation was evident in the inner but not in the outer layer. PMID- 7771541 TI - A noninvasive comparative study of myocardial strains in ischemic canine hearts using tagged MRI in 3-D. AB - Regional reduction in myocardial function has long been utilized for noninvasive detection and localization of ischemic regions in the left ventricle. In this study, we compared the ability of 13 different myocardial strain indexes to discriminate between ischemic and nonischemic tissue. Using magnetic resonance imaging with tagging and three-dimensional reconstruction, we noninvasively tracked the deformation of 24 myocardial cuboids in each of nine canine hearts with acute ischemia induced by coronary artery ligation. Monastral blue staining was used for postmortem assessment of ischemia. The ability of each index to discriminate between normal and ischemic zones was evaluated using the "t" statistic. The best discrimination was obtained by the endocardial area strain [t = 7.5 +/- 3.0 (SD)], a local measure of systolic shrinkage on the endocardial surface, and by the magnitude of the endocardial principal strain (t = 7.0 +/- 1.9). Transmural wall thickening (t = 6.1 +/- 2.3) was the third best functional index. The same three indexes correlated most closely with perfusion, as assessed by monastral blue staining. These findings imply that these are the preferable functional indexes for mapping of ischemic myocardial regions. PMID- 7771542 TI - Adult cardiomyocytes express functional high-affinity receptors for basic fibroblast growth factor. AB - As a first step in addressing the question of function for basic fibroblast growth factor (bFGF) in the adult myocardium, expression of bFGF receptors by adult rat myocytes was investigated. Cross-linking of 125I-labeled bFGF to purified sarcolemmal vesicles from adult hearts indicated specific binding to 90- to 104-kDa proteins, whereas equilibrium binding studies revealed the presence of "low"-affinity (1 nM) and "high"-affinity (115 pM) sites. Adult myocytes were found to express short and long variants of bFGF receptor 1 (FGFR-1, tyrosine kinase) mRNA. Adult heart overall levels of FGFR-1 mRNA were decreased by about one-third of corresponding fetal values. Several lines of evidence indicated that bFGF receptors in adult cardiomyocytes in situ and/or in isolation are functional. Isolated adult myocytes were found to be capable of heparin-resistant internalization of 125I-labeled bFGF, to lose their viability after interaction with bFGF-saporin (a mitotoxin known to kill cells after entry via the bFGF receptor), and to respond to bFGF by activation of mitogen-activated protein kinase. In addition, introduction of exogenous bFGF into the myocardium by Langendorff perfusion resulted in stimulation of tyrosine phosphorylation in association with cardiomyocyte intercalated disks, as assessed by immunofluorescence. It is concluded that adult cardiomyocytes express functionally coupled high-affinity bFGF receptors and that they are capable of a biologic response to bFGF in vivo. PMID- 7771543 TI - Effects of repetitive vagal stimulation on heart rate and on cardiac vasoactive intestinal polypeptide efflux. AB - In dogs anesthetized with alpha-chloralose, we assessed the "vagally induced tachycardia" elicited by successive 2-min periods of intense vagal stimulation (0.5 ms, 10 mA, 20 Hz) after we had blocked the animals' muscarinic and beta adrenergic receptors with atropine and propranolol, respectively. We found that the tachycardia produced by the successive vagal stimulations progressively decreased to < 20% of the initial tachycardia response within 84 min. We also observed that the chronotropic response to vasoactive intestinal polypeptide (VIP) injected into the sinus node artery after the vagal stimulation regimen did not differ significantly from the response to the same dose of VIP injected prior to vagal stimulation. This finding indicates that the postjunctional responsiveness of the cardiac pacemaker cells had not diminished over the course of the vagal stimulation regimen. In isolated, perfused right atrial preparations, we observed a close correlation between the efflux of VIP from the atrial tissues and the chronotropic responses to vagal stimulation. Our results support the hypotheses that 1) VIP is a mediator of vagally induced tachycardia, 2) the reduction in VIP efflux is associated with a diminished vagally induced tachycardia, and 3) the reduced efflux of VIP probably reflects a diminution in neuronal release, perhaps by depletion of this peptide from the vagus nerve endings consequent to the prolonged neural stimulation. PMID- 7771544 TI - Sarcoplasmic reticulum Ca2+ pumps in heart and diaphragm of cardiomyopathic hamster: effects of perindopril. AB - The polymyopathy of the Syrian hamster is associated with alterations of cellular calcium regulation and contractile performance of cardiac and skeletal muscles and, in particular, the diaphragm. Angiotensin-converting enzyme (ACE) inhibitors have been shown to preserve contractile performance. Therefore we analyzed the expression of the genes coding for the sarco(endo)plasmic reticulum Ca(2+) adenosinetriphosphatase (SERCA) in heart and diaphragm of the cardiomyopathic Syrian hamster (CSH) from the dilated strain Bio 53-58, and we tested the influence of ACE inhibition on accumulation of the different SERCA mRNAs. In the diaphragm of healthy hamsters, two SERCA mRNA isoforms were present: SERCA 1 and SERCA 2. At 6 mo of age, the myopathic process resulted in decreased levels of SERCA 1, whereas the level of SERCA 2 was unchanged. The ACE inhibitor perindopril (1 mg.kg-1.day-1), administered by force feeding from 1 to 6 mo of age, had no effect on the SERCA 1 mRNA level. In heart, the myopathy was associated with a depressed level of SERCA 2 mRNA in 9- but not in 6-mo-old animals. Perindopril treatment from 6 to 9 mo reversed cardiac hypertrophy and the relative decrease in SERCA 2 mRNA level. Preventive treatment with perindopril from 1 to 9 mo tended to prevent (not significantly) the development of cardiac hypertrophy and reduction in SERCA gene expression. In conclusion, the myopathic process affects SERCA gene expression in the diaphragm and subsequently in the heart. Perindopril treatment can prevent SERCA mRNA loss in heart but not in diaphragm. PMID- 7771545 TI - Platelet-activating factor increases vascular resistance in rat hindquarters by thromboxane A2. AB - The effects of platelet-activating factor (PAF) on vascular resistance and capillary permeability were studied in the isolated rat hindquarter. Six groups were studied (n = 30): control; PAF alone (1.4 microM); and PAF (1.4 microM) pretreated with ibuprofen (30 mg/kg), thromboxane A2 (TxA2)-receptor antagonist (BM-13505, 2 mg/kg), PAF-receptor antagonist (WEB-2086, 5 mg/kg), or dexamethasone (5 mg/kg). The vascular resistance was calculated, and the reflection coefficient (sigma) was determined as an index of capillary permeability. Exogenous PAF caused a threefold increase in vascular resistance peaking at 5 min and a 2.5-fold increase in capillary permeability. The increased vascular resistance caused by PAF alone was significantly attenuated by ibuprofen, BM-13505, and dexamethasone. The PAF-induced permeability was neither attenuated by ibuprofen nor BM-13505. However, both the increased vascular resistance and permeability were blocked and attenuated by WEB-2086 and dexamethasone, respectively. We conclude that TxA2 mediates the PAF-induced increased vascular resistance; however, the increased vascular permeability is independent of the formation of TxA2 in the isolated hindquarter. PMID- 7771547 TI - EDRF and norepinephrine-induced vasodilation in the canine coronary circulation. AB - Experiments were performed to characterize the role of endothelium-derived relaxing factor (EDRF) in coronary vasodilation caused by norepinephrine. The circumflex or left anterior descending coronary artery was cannulated and pump perfused with constant pressure or constant flow in closed-chest anesthetized dogs. Prostaglandin synthesis was blocked with ibuprofen. During constant pressure perfusion, EDRF inhibition with intracoronary N omega-nitro-L-arginine (L-NNA) did not affect the vasodilation due to nitroglycerin (an endothelium independent process). However, L-NNA did significantly inhibit (P < 0.001) the vasodilation due to acetylcholine (an endothelium-dependent process). In response to bolus injections of norepinephrine, EDRF inhibition with L-NNA significantly reduced coronary vasodilation (P < 0.001). This inhibition was partially reversed with L-arginine infusion. To determine whether an increase in shear stress due to an increase in flow was the stimulus for EDRF release, experiments were performed during constant-flow conditions. Vasodilation caused by nitroglycerin was not inhibited by L-NNA, but EDRF inhibition did blunt acetylcholine-induced vasodilation significantly (P < 0.001) during constant-flow perfusion. During EDRF inhibition with L-NNA, vasodilation due to norepinephrine was not significantly altered when coronary flow was held constant (P = 0.19). In conclusion, EDRF plays a role in norepinephrine-induced coronary vasodilation that is largely flow dependent. PMID- 7771546 TI - Effects of L-arginine analogues on vasomotion of isolated porcine coronary arteries. AB - L-Arginine analogues have been widely used to examine the role of endothelium derived nitric oxide (NO) in vascular responses; however, the effects of the agents on coronary vasomotion are not fully understood. In this study, we examined the effects of the analogues on vasomotion of isolated porcine coronary arteries. Strips of the porcine coronary artery were suspended for isometric tension recording in Krebs-Henseleit solution. L-Arginine analogues, N omega nitro-L-arginine methyl ester (L-NAME, 10(-9)-10(-3) M), NG-monomethyl-L-arginine (L-NMMA, 10(-9)-10(-3) M), and NG-nitro-L-arginine (L-NNA, 10(-9)-10(-3) M), caused dose-dependent contractions, which were greater in strips with than in those without endothelium. Those endothelium-dependent contractions were almost abolished by indomethacin (10(-5) M) and FeCl2 (10(-3) M). The latter reduces prostaglandin H2 to 12-heptadecatrienoic acid, which has no vasoconstrictor effect. These results indicate that the L-arginine analogues cause endothelium dependent contractions that are mediated by prostaglandin endoperoxides and suggest that they have properties other than simple inhibition of NO synthesis in porcine coronary arteries. PMID- 7771548 TI - Solvent drag of LDL across mammalian endothelial barriers with increased permeability. AB - We investigated the mechanisms of hamster low-density lipoprotein (LDL) transport across the endothelial barrier in individually perfused venular microvessels in hamster mesentery. These experiments are the first to use microperfusion techniques and quantitative fluorescence microscopy to investigate LDL transport across mammalian microvessel endothelium. The apparent permeability coefficient for hamster LDL, PsLDL, rose from 2.7 x 10(-7) cm/s at control to 23.2 x 10(-7) cm/s at the peak of the biphasic increase in microvessel permeability after exposure of the vessels to 100 microM histamine. Close to the peak, PsLDL rose 1.85 x 10(-7) cm/s for every centimeter of H2O increase in hydrostatic pressure. Thus, at a mean pressure of 11.3 cmH2O, 90% of the LDL flux was coupled to transendothelial water flow by a solvent drag mechanism. The corresponding solvent drag reflection coefficient for hamster LDL was estimated to be approximately 0.8. These results are consistent with sieving hamster LDL (effective radius 14.9 nm) through equivalent pores of approximately 22 nm radius. Similar results were found with human LDL (effective radius 13.2 nm) in hamster microvessels. The results provide a bridge between studies of LDL transport across cultured endothelial barriers, where high diffusive permeability coefficients to LDL may obscure the contributions of solvent drag, and studies in whole animals, where the consequences of sieving of LDL at the vessel wall, even in the high permeability state, have not received much attention. PMID- 7771549 TI - Role of chloride currents in repolarizing rabbit atrial myocytes. AB - Rabbit atrial cells manifest a prominent transient outward K+ current (Ito1), but this current recovers slowly from inactivation and is unlikely to be important at physiological rates (3-5 Hz). Depolarization of rabbit atrial cells also elicits a transient Ca(2+)-dependent outward Cl- current (Ito2). To compare the relative magnitude of these transient outward currents at various rates, we applied whole cell voltage-clamp techniques to isolated rabbit atrial myocytes. Whereas peak Ito1 exceeded Ito2 at slow rates (0.1 Hz), Ito1 was strongly reduced as rate was increased (by 97 +/- 2%, mean +/- SE, at 4 Hz), while Ito2 was slightly reduced (by 28 +/- 4%, 4 Hz). The reversal potential of transient outward tail currents at 0.07 Hz was -49 +/- 9 mV, while at 2.5 Hz the reversal potential became -18 +/ 7 mV (calculated Cl- reversal potential -18 mV). The addition of the Cl- transport blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 150 microM) or the replacement of external Cl- with methanesulfonate inhibited a large part of the transient outward current elicited by depolarization at 4 Hz. DIDS and Cl- replacement increased action potential duration in both single rabbit atrial cells and multicellular rabbit atrial preparations. We conclude that the Ca(2+)-dependent Cl- current is substantially larger than the transient K+ current at physiological rates in the rabbit and is likely to play a more important role in action potential repolarization than the latter current in this tissue in vivo. PMID- 7771550 TI - Contributions of sickle hemoglobin polymer and sickle cell membranes to impaired filterability. AB - Sickle cell anemia is a disease of abnormal rheology caused by acute and reversible, as well as chronic and irreversible, changes in the properties and deformability of sickle erythrocytes. Deformability is determined by several factors, including intracellular sickle hemoglobin polymerization, the abnormal membrane properties of sickle cells, and the abnormal rheological properties of the soluble concentrated hemoglobin solution within dense sickle red blood cells. In this study, we used a 5-microns pore nickel mesh filter to evaluate quantitatively the effects of these factors on the filterability of erythrocytes containing sickle hemoglobin. We used sickle trait and sickle/beta(+)-thalassemia cells, because they have minimal membrane abnormalities or density heterogeneity, to investigate the effects of polymer formation on rheological properties. We found that filterability of these cells is sensitive to small amounts of intracellular polymer and that impaired filtration is linearly related to oxygen dependent polymer formation, up to a polymer fraction of 0.3. By increasing the proportion of dense cells in populations of normal cells or cells from individuals with sickle syndromes and equilibrating these cells with gas ligands, we estimate that polymerization, even at 95% saturation, contributes twice as much to impaired filterability of sickle erythrocytes as the abnormal membranes in homozygous sickle cell disease. At lower saturation values, the effects of polymer are even greater. The viscosity of the concentrated hemoglobin in dense cells had the smallest effect, over physiologically relevant saturation values. These results emphasize the importance of sickle hemoglobin polymerization in the pathogenesis of sickle cell disease and should help define its pathophysiology and responses to therapy in quantitative terms. PMID- 7771551 TI - Potentiation of angiotensin II-stimulated vascular contraction by lithium. AB - Previous studies have suggested that lithium prolongs or enhances vascular contractions stimulated by alpha-adrenergic agents. The present study was performed to determine whether a similar phenomenon occurs with angiotensin II (ANG II)-stimulated contractions and whether this phenomenon results from interactions with the phosphoinositide signaling system. Contractions of rat aortic rings with 100 nM ANG II were 38% greater in the presence of 20 mM LiCl than in its absence (0.47 +/- 0.07 vs. 0.34 +/- 0.05 g tension/mg dry tissue wt, P < 0.01). The effects of lithium on inositol phosphate responses, diacylglycerol responses, and intracellular calcium concentration on single or repeated stimulations with ANG II were then examined in vascular smooth muscle cells cultured from rat aorta. Cells exposed twice to 100 nM ANG II contained 50% lower inositol trisphosphate levels (InsP3) and 10% lower diacylglycerol levels than cells exposed to ANG II only once. LiCl or lithium acetate abolished these desensitizations in a concentration-dependent manner. Similarly, InsP3 and diacylglycerol responses to a single exposure of ANG II were heightened by lithium (by 75 and 25%, respectively), and the duration of the responses was prolonged by lithium (5- and 2-fold, respectively). In contrast, ANG II stimulated calcium transients were not enhanced or prolonged by lithium, nor was desensitization of ANG II-stimulated cytosolic calcium mobilization upon serial exposures abolished by lithium. When ring contraction studies were repeated in the presence of the protein kinase C inhibitor staurosporine (150 nM), lithium no longer potentiated ANG II contractions [0.38 +/- 0.03 (control) vs. 0.35 +/- 0.06 g tension/mg dry tissue wt (lithium)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771552 TI - Electrophysiological effects of alpha 2-adrenergic stimulation in canine cardiac Purkinje fibers. AB - The effects of alpha 2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 microM l norepinephrine + 0.5 microM dl-propranolol (NE+P) from baseline values of 166 +/- 7 and 249 +/- 9 (SE) ms (n = 7) to 174 +/- 7 and 265 +/- 9 ms, respectively (P < 0.05 for both). Selective alpha 2-blockade with 0.01 microM yohimbine (YO) reduced this prolongation by NE+P in APD50 and APD90 to 169 +/- 7 and 256 +/- 8 ms, respectively (P < 0.05 compared with NE+P). Additional selective alpha 1 blockade with 0.01 microM prazosin (PZ) completely blocked the effects of NE+P, returning APD50 and APD90 to 163 +/- 7 and 250 +/- 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 microgram/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 +/- 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE+P, but the effects of PZ were intact. The effects of alpha 2-stimulation on beta-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE+PZ (beta- + alpha 2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE+PZ+YO (unopposed beta-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under beta-stimulation, could no longer be elicited in the presence of beta- + alpha 2-stimulation. These results suggest that the postjunctional alpha 2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by beta-adrenergic stimulation. PMID- 7771553 TI - Whole cell membrane currents in cultured pig endocardial endothelial cells. AB - The whole cell mode of the patch-clamp technique was applied to cultured endocardial endothelial cells from the porcine right ventricle to study their electrophysiological properties. With isotonic pipette and bathing solutions (300 310 mosmol/kgH2O), single endocardial endothelial cells had resting membrane potentials ranging from -20 to -90 mV (mean = -55 +/- 20 mV, n = 48). In voltage clamp experiments, the main membrane current was an inwardly rectifying K+ current with all characteristics described for the inwardly rectifying K+ current in vascular endothelium. Outward currents at positive clamp potentials were small, but when cell swelling was induced by means of a hypertonic pipette or hypotonic bathing solution and ATP (5 mM) was present in the pipette solution, a large outwardly rectifying current developed. This volume-activated current was insensitive to extracellular K+ or Na+ concentration variations but sensitive to changes in extracellular Cl- concentrations. It was inhibited in the presence of 4,4'-diisothiocyanostilbene-2,2 disulfonic acid (100-300 microM) and flufenamic acid (50-100 microM). Volume-activated Cl- channels are different from the stretch-activated cationic channels described in vascular endothelium and might be involved in the regulation of cell volume or the response to mechanical stretch. PMID- 7771554 TI - Lysophosphatidic acid alters cerebrovascular reactivity in piglets. AB - Effects of the lipid mediator lysophosphatidic acid (LPA) were studied on the cerebral circulation of newborn pigs using closed cranial windows. Topical application of synthetic LPA caused dose-dependent vasoconstriction and inhibited vasodilation to hypercapnia and isoproterenol. These vasodilators elicited a rise in the adenosine 3',5'-cyclic monophosphate (cAMP) content of the cerebrospinal fluid, which was inhibited dose dependently by LPA. Pertussis toxin (1 microgram/ml) completely abolished LPA-induced vasoconstriction and the altered vascular reactivity, and LPA no longer decreased cAMP. Electrophysiological recording of currents evoked by LPA-like lipids in Xenopus oocytes showed that cerebrospinal fluid is normally devoid of LPA-like factors. In contrast, the amount of LPA-like factors generated 4 days after intrathecal injection of autologous blood was in the range of 1-10 microM LPA equivalents. The data indicate that LPA-like bioactive mediators were generated in an intracranial hematoma model and that these phospholipids might play a role in the pathophysiology of altered vascular reactivity often found in posthemorrhagic conditions and could also contribute to the development of posthemorrhagic vasoconstriction. PMID- 7771555 TI - Selective reduction of PVR by inhalation of a cGMP analogue in a porcine model of pulmonary hypertension. AB - Selective reduction of pulmonary vascular resistance (PVR) remains a therapeutic goal for the treatment of pulmonary hypertension, but current therapeutic options remain limited. Although the gas nitric oxide (NO) selectively dilates the pulmonary vascular bed, it requires special equipment for administration, has a short biologic half-life, and is potentially toxic. We hypothesized that stimulation of the NO pathway at the level of its second messenger, guanosine 3',5'-cyclic monophosphate (cGMP), by targeted pulmonary delivery of a membrane permeable nonhydrolyzable cGMP analogue would cause selective pulmonary vasodilation. Pulmonary hypertension was induced in 21 pigs by the intravenous infusion of a thromboxane A2 analogue (9,11-dideoxy-9 alpha,11 alpha epoxymethanoprostaglandin F2 alpha). Inhaled 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) lowered PVR in a time- and dose-dependent manner, with maximal effect achieved after 20 min. Compared with physiological saline control, 8-BrcGMP inhalation (3.0 micrograms/kg) lowered PVR by 25 +/- 3% (P < 0.01), whereas there was no significant decline in systemic vascular resistance (4 +/- 6%); mean pulmonary arterial pressure declined 13 +/- 3% (P < 0.01), whereas there was little change in mean arterial pressure; cardiac output increased 10 +/ 4% (P < 0.05). PVR did not decrease after inhalation of noncyclic 8 bromoguanosine 5'-monophosphate, indicating that stimulation of the NO-cGMP pathway beyond the level of NO results in pulmonary vasodilation independent of stimulation of purinergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771556 TI - Ischemic preconditioning attenuates capillary no-reflow induced by prolonged ischemia and reperfusion. AB - Ischemic preconditioning (IPC) refers to a phenomenon in which a tissue is rendered resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. The purposes of this study were to determine whether IPC would reduce the extent of capillary no-reflow in postischemic skeletal muscle and whether the protective effect of IPC was due to activation of ATP-sensitive potassium (KATP) channels. To address the first aim, capillary perfusion was assessed in vascularly isolated canine gracilis muscles subjected to 4.5 h of continuous perfusion, 4 h of ischemia followed by 30 min of reperfusion (I-R), and IPC (4 periods of 5 min ischemia followed by 5 min reperfusion) before I-R. I-R was associated with a reduction in the number of patent capillaries per fiber (0.6 +/- 0.1) relative to nonischemic control muscles (2.5 +/- 0.1), an effect that was attenuated by IPC (1.3 +/- 0.1 patent capillaries fiber). A role for KATP channels in the protective effect of IPC is supported by the observation that administration of a KATP channel antagonist (glibenclamide) 10 min before induction of IPC abolished the protective effect of preconditioning (0.6 +/- 0.1 patent capillaries/fiber). On the other hand, treatment of nonpreconditioned muscles with a KATP channel agonist (pinacidil) mimicked the protection afforded by IPC (1.2 +/- 0.1 patent capillaries/fiber). Moreover, the protective effect of pinacidil treatment was reversed by prior administration of glibenclamide (0.5 +/- 0.1 patient capillaries/fiber). These data indicate that IPC improves postischemic capillary perfusion by a mechanism that involves activation of KATP channels. PMID- 7771557 TI - Inhibition of arteriole alpha 2- but not alpha 1-adrenoceptor constriction by acidosis and hypoxia in vitro. AB - We have found that hypoxia and acidosis inhibit constriction by alpha 2D adrenoceptors but not by alpha 1D-adrenoceptors on arterioles of rat skeletal muscle, facilitating local metabolic control of blood flow. When activated by full agonists like norepinephrine, this alpha 2D-constriction relies on Ca2+ influx through dihydropyridine-sensitive, voltage-operated Ca2+ channels (VOC), while alpha 1D-constriction does not. The purpose of the present study was to examine the dose sensitivity of this selective metabolic inhibition of alpha 2D constriction and determine whether inhibition of VOCs is involved. Changes in lumen diameter of microcannulated arterioles isolated from rat skeletal muscle (107 +/- 3 microns control diam) were measured by videomicroscopy for bath-added agents. Decreases in pH (7.4-7.0) or PO2 (70 to 10 mmHg) caused graded inhibition of alpha 2D-adrenoceptor constriction (UK-14304 plus prazosin); the half-maximum inhibitory concentration for acidosis was 7.1 and for PO2 was 24 mmHg. alpha 1D Adrenoceptor constriction by the respective full and partial alpha 1-agonists, phenylephrine (PE) and St-587 (both plus rauwolscine), was unaffected. Because St 587 but not PE constriction was dependent on VOC activation, the sensitivity of alpha 2D- but not alpha 1D-constriction to acidosis and hypoxia appeared to be independent of reliance on VOCs. This was examined directly; contractile sensitivity to KCl and the VOC agonist, SDZ-202-791, was unaffected by pH 7.0 or PO2 10 mmHg. These data suggest that alpha 2D-constriction is sensitive to inhibition by hypoxia and acidosis through a mechanism that does not involve direct blockade of dihydropyridine-sensitive Ca2+ channels. PMID- 7771558 TI - Episodic hypertension due to autonomic dysreflexia in acute and chronic spinal cord-injured rats. AB - Spinal cord injury results in abnormal sympathetic control of the cardiovascular system, consisting of exaggerated reflexes with resulting hypertension and bradycardia that has been termed autonomic dysreflexia. We studied changes in arterial pressure and heart rate caused by colon or urinary bladder distension in unanesthetized acute (7 day) and chronic (30 day) spinal cord-injured rats to evaluate the time course of these responses in an animal model of spinal cord injury. In conscious control rats colon and bladder distension caused brief (2-10 s) pressor responses of 10 mmHg associated with tachycardia and escape reactions. Colon distension in spinal cord-injured rats increased arterial pressure by 41 +/ 2, 22 +/- 3; and 49 +/- 5 mmHg at 24 h and 7 and 30 days after cord transection, respectively. These responses lasted 30 s-5 min and were accompanied by bradycardia. Distension of the urinary bladder caused similar responses in spinal rats after 24 h and 30 days of cord transection. We propose that the initial responses may be related to loss of descending inhibition of spinal reflexes but that plastic changes in the spinal cord is one of the mechanisms for the autonomic dysreflexia occurring 1 mo after injury. PMID- 7771560 TI - Large artery remodeling after myocardial infarction. AB - Rats with myocardial infarction (MI) after coronary artery ligation (n = 75) and sham operated rats (n = 40) were treated with captopril (2 g/l drinking water), hydralazine (80 mg/l drinking water), or untreated water for 3 wk. Arterial hemodynamics, carotid artery mechanical properties, and water permeability were measured. Arterial wall stress and interstitial fluid velocity were calculated. In infarcted rats, the characteristic impedance at matched pressure was increased by 135% (P < 0.02); captopril and hydralazine decreased characteristic impedance (P < 0.015). MI altered the material constants; captopril but not hydralazine normalized these constants. Water permeability was increased by 221% (P < 0.001) in infarcted rats; captopril but not hydralazine reversed water permeability (P < 0.05). MI resulted in a 59% increase (P < 0.05) in the arterial collagen area and a 22% decrease (P < 0.05) in the media thickness. Captopril but not hydralazine decreased (P < 0.03) collagen area. In conclusion, 1) arterial remodeling defined by alterations in the passive mechanical properties, water permeability, and structure occurs in rats after MI; and 2) captopril but not hydralazine reverses the arterial remodeling. PMID- 7771559 TI - Endothelin-1 and its binding sites are upregulated in pressure overload cardiac hypertrophy. AB - The purpose of this study was to determine whether endothelin and endothelin receptors play an important role in the development of cardiac hypertrophy due to pressure overload in vivo. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats. Hemodynamic parameters and plasma and ventricular concentrations of endothelin-1 (ET-1) were measured in control unoperated rats, and 30 min, 2 and 6 h, and 1 and 8 days after operation in pressure overload rats and sham-operated rats. The density and dissociation constant of ET-1 binding sites were also measured in control rats and 1 and 8 days after pressure overload and sham operation. Additionally, in situ mRNA hybridization for preproendothelin-1 (preproET-1) mRNA was performed to determine which cells were responsible for increased ET-1 levels. Ventricular ET 1 levels increased markedly on day 8 of pressure overload, whereas plasma ET-1 levels increased transiently only 30 min after operation, quickly returning to control level. In addition, ventricular ET-1 levels on day 8 showed a significant positive correlation with the degree of cardiac hypertrophy. In situ mRNA hybridization revealed that cardiac myocytes expressed preproET-1 mRNA in hypertrophied hearts in vivo. In accord with the elevation of ventricular ET-1 levels, the density of ET-1 binding sites was increased significantly, without affecting their binding affinity, on day 8 of pressure overload. These data are compatible with the hypothesis that increases in locally produced ET-1 and the density of ET-1 binding sites have an important relationship with the development of cardiac hypertrophy in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771561 TI - Effects of chronic supraventricular pacing tachycardia on relaxation rate in isolated cardiac muscle cells. AB - Chronic supraventricular pacing tachycardia (SVT) causes abnormalities in both ventricular and cellular relaxation. The mechanisms causing these abnormalities have not been fully determined. To examine two of the possible mechanisms, a decrease in restoring force or an impairment of the intrinsic myocardial relaxation process, cardiocytes were enzymatically isolated from the left ventricle of pigs subjected to left atrial pacing at 240 beats/min for 3 wk and normal control pigs. SVT caused a decrease in the extent of cardiocyte shortening and the velocity of cardiocyte lengthening. To determine whether the changes in the relaxation velocity merely reflected a concomitant decrease in the extent of cardiocyte shortening (and a resultant decrease in restoring forces) or, in addition, reflected impairment in intrinsic relaxation properties, the relation between cardiocyte relaxation velocity and cardiocyte shortening extent was examined. There was a direct relation between relaxation velocity and shortening extent in both control and SVT cardiocytes. However, SVT decreased the relaxation velocity at any common extent of shortening and decreased the slope of the direct relation (slope 5.91 in control vs. 3.51 s-1 in SVT, P < 0.05). Therefore, these data suggested that SVT caused a primary impairment in the intrinsic myocardial relaxation process independently of a decrease in restoring force. PMID- 7771562 TI - Cardiac-cardiovascular reflexes induced by hydrogen peroxide in cats. AB - We have shown previously that reactive oxygen species stimulate abdominal sympathetic afferents to cause reflex cardiovascular activation. Because myocardial ischemia and reperfusion also generate reactive oxygen species, we investigated the possibility that cardiovascular reflexes could be induced by topical application of H2O2 to the anterior or posterior ventricular surface in cats anesthetized with alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR), left ventricular (LV) pressure, aortic flow (AF), and first derivative of LV pressure at 40 mmHg developed pressure (LV dP/dt40) were monitored. H2O2 (44 and 130 mumol) significantly increased MAP but not HR or LV dP/dt40 in intact cats (n = 8). Application of H2O2 (44 mumol) significantly increased MAP (129 +/- 9 to 152 +/- 10 mmHg), HR (240 +/- 11 to 245 +/- 10 beats/min), AF (191 +/- 13 to 212 +/- 17 ml/min), total peripheral resistance (0.68 +/- 0.13 to 0.73 +/- 0.04 peripheral resistance units), and LV dP/dt40 (2,666 +/- 145 to 3,012 +/- 205 mmHg/s) after bilateral cervical vagotomy (n = 6). These H2O2-induced excitatory responses were abolished after bilateral T1-T4 ganglionectomy. In six additional cats, H2O2 (44 mumol) significantly decreased MAP (114 +/- 5 to 102 +/- 5 mmHg), HR (207 +/- 7 to 190 +/- 7 beats/min), and LV dP/dt40 (2,776 +/- 168 to 2,600 +/- 153 mmHg/s) after sympathectomy. These depressor responses were eliminated after vagotomy. The magnitude of the cardiovascular reflexes was increased or decreased in a dose-dependent fashion in vagotomized or sympathectomized cats, respectively, over a range of 440 nmol to 44 mumol H2O2. Application of H2O2 to the anterior or posterior ventricular surface resulted in similar pressor or depressor reflexes. Dimethylthiourea and deferoxamine abolished pressor or depressor responses evoked by H2O2 in both vagotomized (n = 8) and sympathectomized (n = 8) cats. We conclude that reactive oxygen species, particularly the hydroxyl radical, can participate in activating cardiac afferents responsible for reflex cardiovascular responses during myocardial ischemia and reperfusion. An inhibitory reflex is transmitted through vagal afferents, whereas an excitatory reflex is conducted by sympathetic cardiac afferents. PMID- 7771563 TI - Left ventricular mechanics in arrested dog heart: effects of ventricular interaction and vascular volumes. AB - The present study was designed to determine the effects of right heart pressure on the compliance of the left ventricle (LV). The studies were conducted on isolated, blood-perfused, potassium-arrested dog hearts with vasomotor tone either present (n = 5) or absent (n = 8). A balloon was used to control LV volume, whereas right heart (RHP) or coronary sinus (CSP) pressures were controlled via a column placed in the right heart or coronary sinus, respectively. Control of CSP independently of RHP allowed us to assess the relative contribution of coronary venous pressure to changes in LV compliance under conditions of elevated RHP. LV volume and compliance at a LV pressure of 15 mmHg (V15 and C15, respectively) were calculated to quantify the shift and slope changes of the LV pressure-volume (P-V) relationships. V15 and C15 decreased with vasomotor tone present from 52.8 +/- 1.4 ml and 1.7 +/- 0.1 ml/mmHg at control, to 43.3 +/- 2.1 ml and 1.4 +/- 0.1 ml/mmHg (P < 0.05) with RHP = 0 and 20 mmHg, respectively. Similar effects were obtained with vasodilation, but C15 was significantly lower relative to autoregulation but C15 was significantly lower relative to autoregulation (1.0 +/- 0.1 at control RHP, P < 0.05). Elevation of CSP with vasomotor tone resulted in an upward shift in the LV P-V relationship: V15 decreased from 53.4 +/- 2.1 at CSP = 0 mmHg to 50.9 +/- 1.6 ml at CSP = 20 mmHg (P < 0.05). After vasodilation there was no detectable shift in the LV P-V relationship with elevation of CSP. PMID- 7771564 TI - Roles of colloidal molecules in Starling's hypothesis and in returning interstitial fluid to the vasa recta. AB - To begin to understand the role of colloidal molecules, a simple question requires an answer: How do the solutes alter water in an aqueous solution? Hulett's answer deserves attention, namely, the water in the solution at temperature and external pressure applied to solution (T,pe1) is altered in the same way that pure water is altered by reducing the pressure applied to it by the osmotic pressure of the water at a free surface of the solution. It is nonsense to relate the lower chemical potential of water in a solution to a lower fugacity or to a lower activity of the water in the solution, since these terms have no physical meaning. It is also incorrect to attribute the lower chemical potential of the water to a lower concentration of water in the solution. Both claims are derived from the teachings of G. N. Lewis and are erroneous. Textbook accounts of the flux of fluid to and from capillaries in the kidney and other tissues are inadequate, if not in error, as they are based on these bogus claims. An understanding of the process by which colloidal proteins in plasma affect the flux of nearly protein-free fluid across the capillary endothelium must start with insights derived from the teachings of G. Hulett and H. Dixon. The main points are 1) colloidal molecules can exert a pressure against a membrane that reflects them and, thereby, displace a distensible membrane; 2) they can alter the internal tension of the fluid through which they diffuse when there is a concentration gradient of the molecules; and 3) only by these means can they influence the flux of plasma fluid across the capillary endothelium. However, the process is complex, since both the hydrostatic pressure and protein concentrations of fluids inside and outside the capillary vary with both position and time as plasma flows through the capillary. PMID- 7771565 TI - A chemoreflex model of relation between blood pressure and heart rate in sleep apnea syndrome. AB - In obstructive sleep apnea syndrome (OSAS), pronounced low-frequency (LF) oscillations of blood pressure and interbeat interval (I) occur during recurrent apneas. We investigated the time relations between LF oscillations of diastolic pressure (D) and I in 12 patients with OSAS by means of spectral analysis. A high coherency between I and D was found, allowing a description of the relation by gain and phase. Oscillations in I and D were almost in counterphase in the LF range. Simple physiological models were implemented to interpret the observed features of LF oscillations. Model 1 describes the vagal and sympathetic influence by the carotid body chemoreflex on the circulation. From derivation of the frequency response of this model, gain and phase relations were obtained as would be expected from the action of the chemoreflex. We found that a range of phase relations can be induced by this reflex, depending on the relative vagal and sympathetic efferent influence on the circulation. This range of phase relations was indeed observed in 10 patients. Extended models that also included the orienting reflex (model 1a) or the baroreflex and a mechanical influence of breathing on the circulation (model 2) could not fit the data without a major contribution of the chemoreflex. We conclude that the relation between LF oscillations in I and D in OSAS can be explained by assuming that stimulation of the carotid body chemoreflex is the main source of these oscillations. PMID- 7771566 TI - Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. AB - The purpose of the present study was to investigate a possible role of opioid receptors in ischemic preconditioning (PC). To test this hypothesis, anesthetized, open-chest, male Wistar rats were subjected to five different protocols. In group I, the control group was subjected to 30 min of left coronary artery occlusion and 2 h of reperfusion. In group II, ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. In group III, naloxone (NL, 3 mg/kg iv), a nonselective opioid antagonist, was given to nonpreconditioned rats 10 min before the 30-min occlusion period. Finally, NL was administered 10 min before preconditioning (NL + PC, group IV) or immediately after the last 5-min preconditioning period (PC + NL, group V). Infarct size (IS) as a percentage of the area at risk (AAR) (IS/AAR) was determined by 2,3,5 triphenyltetrazolium chloride staining. PC resulted in a marked reduction in myocardial IS from 45 +/- 5 to 8 +/- 1 (P < 0.05). NL treatment before or immediately after PC abolished this protective effect; however, NL had no effect on IS in non-PC rats. These results are the first to support the hypothesis that activation of opioid receptors may play an important role in ischemic PC in the rat myocardium. PMID- 7771567 TI - Left ventricular pressure is an important determinant of coronary oscillatory flow amplitude. PMID- 7771568 TI - Metabolic adaptations for desert survival in the Bedouin goat. AB - Energy conservation is a key adaptation for desert survival in the Bedouin goat. When food is scarce, metabolism is reduced and body weight can be maintained indefinitely on less than one-half of normal intake. We hypothesized that metabolism would be turned down during both rest and exercise, but it was not. It was low when animals rested and returned to normal during exercise. We expected catecholamines and thyroid hormones would modulate metabolism, but they did not. The reduction in metabolism preceded any change in thyroid hormone concentrations, and infusions of epinephrine did not restore reduced metabolism to normal levels. Finally, we expected the gut would be the major organ system involved in the metabolic reduction because less food is eaten, processed, and absorbed. Contrary to our expectations, we found that muscle is the primary organ system responsible for the reduction. It appears that the adaptations of the Bedouin goat for surviving on limited food supplies involve different organ systems and different modulators to reduce metabolism from those known for other mammals. PMID- 7771569 TI - Light-induced suppression of the rat circadian system. AB - In a constant environment, circadian rhythms persist with slightly altered period lengths. Results of studies with continuous light exposure are less clear, because of short exposure durations and single-variable monitoring. This study sought to characterize properties of the oscillator(s) controlling the rat's circadian system by monitoring both body temperature and locomotor activity. We observed that prolonged exposure of male Sprague-Dawley rats to continuous light (LL) systematically induced complete suppression of body temperature and locomotor activity circadian rhythms and their replacement by ultradian rhythms. This was preceded by a transient loss of coupling between both functions. Continuous darkness (DD) restored circadian synchronization of temperature and activity circadian rhythms within 1 wk. The absence of circadian rhythms in LL coincided with a mean sixfold decrease in plasma melatonin and a marked dampening but no abolition of its circadian rhythmicity. Restoration of temperature and activity circadian rhythms in DD was associated with normalization of melatonin rhythm. These results demonstrated a transient internal desynchronization of two simultaneously monitored functions in the rat and suggested the existence of two or more circadian oscillators. Such a hypothesis was further strengthened by the observation of a circadian rhythm in melatonin, despite complete suppression of body temperature and locomotor activity rhythms. This rat model should be useful for investigating the physiology of the circadian timing system as well as to identify agents and schedules having specific pharmacological actions on this system. PMID- 7771570 TI - Metabolism of erythropoietin in conscious pregnant rats. AB - Circulating erythropoietin (EPO) concentration increases during human and rat gestation, thereby contributing to the expansion of red cell mass. However, the mechanism(s) underlying gestational increases of the hormone is unknown. Our objective was to define whether the elevated EPO levels are secondary to decreased metabolic clearance or to enhanced production. The half-life of the hormone was also measured. A bolus and a constant infusion of 125I-labeled recombinant human EPO (125I-rhEPO) were administered to chronically instrumented conscious pregnant and virgin rats. The metabolic clearance rate of the 125I rhEPO was slightly but significantly higher in gravid rats than in the virgin control animals (0.13 +/- 0.01 vs. 0.10 +/- 0.01 ml/min). The plasma half-life of 125I-rhEPO was 2.9 +/- 0.1 h for the pregnant rats and 2.9 +/- 0.2 h for the virgin controls. To confirm these results obtained by using 125I-rhEPO, EPO-rich plasma was generated in anemic rats and administered to another group of conscious virgin and pregnant rats. The half-life of homologous EPO was 2.9 +/- 0.5 and 3.3 +/- 0.1 h for gravid and virgin rats, respectively (P = NS). We conclude that elevated circulating EPO in rat gestation is secondary to increased biosynthesis and not to decreased metabolic clearance. PMID- 7771571 TI - Lactate influx into red blood cells of athletic and nonathletic species. AB - Transport of lactate across the erythrocyte membrane proceeds by three distinct pathways: 1) nonionic diffusion of lactic acid, 2) inorganic anion exchange (band 3), and 3) a monocarboxylate-specific (MC) carrier mechanism. This study determined the contributions of these three pathways in the red blood cells (RBCs) of "athletic" and "nonathletic" species. Blood samples were obtained from four male animals of each species: 1) Canis familiaris (dogs), 2) Capra hircus (goats), 3) Equus caballus (horses), and 4) Bos taurus (cattle). Contribution of each pathway to total lactate influx was determined by measuring L-[14C]lactate influx into lactate-depleted control RBCs, p-chloromercuribenzenesulfonic acid (PCMBS)-treated (1 mM) RBCs, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-treated (0.2 mM) RBCs at three lactate concentrations ([La] values 1.6, 8.1, and 41 mM). PCMBS blocked MC transport and DIDS blocked the band 3 pathway. Lactate influx into the RBCs of the athletic species was 4-160 times faster (P < 0.05) than influx into the RBCs of the nonathletic species at 8.1 and 41 mM [La] values. Nonionic diffusion was greater in the RBCs of nonathletic animals (approximately 7-25%) than in the RBCs of athletic animals (approximately 4%). A significantly higher percentage of the total lactate influx occurred via the band 3 system in the RBCs from the nonathletic animals (approximately 56-83%) vs. the RBCs from the athletic animals (approximately 6-7%) at all [La] values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771572 TI - Mechanical basis of ANP secretion in beating atria: atrial stroke volume and ECF translocation. AB - To investigate the mechanism by which an increase in pacing frequency or distension increases the secretion of atrial natriuretic peptide (ANP), the changes in atrial volume during contraction (atrial stroke volume), transmural transport of the extracellular fluid (ECF), and ANP secretion were quantified in the beating perfused rabbit atria. The atrium was stimulated by transmural field stimulation or by atrial distension induced by an increase in intraatrial pressure. Atrial stretch and incremental increases in pacing frequency up to 2 Hz activated the secretion of ANP coincident with an increase in atrial stroke volume and the transendocardial translocation of the ECF. These results showed positive relationships between changes in the secretion of ANP and the atrial stroke volume or the translocation of the ECF. The translocation of the ECF was also positively correlated with the change in atrial stroke volume. The accentuated secretion of ANP and translocation of the ECF waned at higher stimulating rates to show a peak value. Even under this condition, the secretion of ANP was a function of the translocation of the ECF. These data suggest that the increases in atrial stroke volume and translocation of ECF are fundamental factors in the ANP stimulation in response to atrial stretch and increases in atrial rate. PMID- 7771573 TI - L-arginine analogues inhibit aldosterone secretion in rats. AB - L-Arginine analogues, e.g., NG-nitro-L-arginine methyl ester (L-NAME), increase arterial pressure and suppress renin release in the rat. On the basis of these observations, it was hypothesized that L-arginine analogues also would attenuate aldosterone secretion. This hypothesis was tested in anesthetized rats treated with L-NAME or NG-nitro-L-arginine (L-NNA, 185 mumol/kg ip). The aldosterone secretion rate, plasma renin activity, and adrenal blood flow were attenuated in rats treated with L-NAME and L-NNA compared with control animals. Similar experiments were performed in anephric rats to examine the effects of L-NAME on aldosterone secretion independent of the circulating reninangiotensin system. The administration of L-NAME reduced adrenal blood flow but failed to reduce aldosterone secretion in these anephric rats. Bilateral nephrectomy reduced plasma renin activity essentially to undetectable levels in these animals. In a third series of experiments, two groups of anephric rats were infused with angiotensin II (3 micrograms/kg body wt iv) to provide a stimulus for aldosterone secretion. Aldosterone secretion and adrenal blood flow were markedly reduced in angiotensin II-infused rats pretreated with L-NAME compared with the control anephric animals infused with angiotensin II. Overall these results suggest that L-arginine analogues attenuate aldosterone secretion by inhibiting the adrenal steroidogenic effects of endogenous or exogenous angiotensin II and/or by reducing plasma levels of renin/angiotensin. PMID- 7771575 TI - Effect of arterially infused catecholamines and insulin on plasma glucose and free fatty acids in carp. AB - Common carp (Cyprinus carpio L.), kept at 20 degrees C, were fitted with an indwelling PE-50 cannula in the dorsal aorta. Hormones dissolved in Ringer saline were arterially infused at a rate of 1 microgram.kg-1.min-1 for epinephrine (Epi), 2 micrograms.kg-1.min-1 for norepinephrine (NE), and 1.33 micrograms.kg 1.min-1 for insulin. INfusion of bovine insulin in carp resulted in a long lasting (24 h) decrease of plasma free fatty acids (FFA; -0.41 +/- 0.06 mM) and glucose levels (-3.14 +/- 0.25 mM) compared with preinfusion levels at t = 0. Both Epi and NE induced a marked hyperglycemia although Epi was more potent (+8.2 +/- 0.9 and +6.9 +/- 0.8 mM, respectively). Plasma FFA levels increased by 0.25 +/- 0.03 mM compared with preinfusion levels on Epi infusion. In contrast, during NE infusion, plasma FFA levels decreased significantly by -0.21 +/- 0.03 mM. Plasma insulin titers did not significantly change during infusion of NE or Epi. It is concluded that the ratio of NE to Epi is the major factor that determines the effect of catecholamines on plasma FFA levels in carp. These results may explain species-dependent different effects of hypoxia on FFA metabolism in fish. PMID- 7771574 TI - Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy. AB - Children and menstruant women are far more likely than men to develop metabolic brain damage from hyponatremia. We evaluated brain adaptation and mortality from hyponatremia in male and female rats of three different age groups. With acute hyponatremia, the mortality was 84% in prepubertal rats vs. 15% in adults and 0% in elderly rats. With chronic hyponatremia, mortality was 13% in adult males vs. 62% in females. Testosterone pretreatment significantly decreased mortality (from 62 to 9% in adult females, and from 100% to zero in prepubertal rats), but estrogen significantly increased mortality (from 13 to 44% in adult males). With acute hyponatremia in adult rats, brain sodium was significantly decreased ( 17%), but in prepubertal rats it was actually increased (+ 37%). Cerebral perfusion during chronic hyponatremia was significantly impaired in adult females vs. males or controls (P < 0.01). Neither vasopressin administration nor chronic hyponatremia induced with desmopressin resulted in any mortality or decrement of cerebral perfusion. Thus age, gender, and the cerebral effects of vasopressin are major determinants of mortality in experimental metabolic encephalopathy. PMID- 7771576 TI - Central nucleus of the amygdala and the development of hypertension in spontaneously hypertensive rats. AB - Electrolytic lesions of the central nucleus of the amygdala (ACe) have been shown to attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Whether this was due to destruction of local neurons and/or fibers is unknown. In the present study, neuronal perikarya in the ACe of 4-wk-old SHR were selectively destroyed with ibotenic acid. In two experiments, each comprising lesioned and sham-lesioned SHR, mean arterial blood pressure (MAP) was measured 7 and 15 wk after operation in the second experiment also at 22 wk. In the first experiment, in which rats were fed ad libitum, lesioned SHR had significantly lower body weights from 5 wk postoperation onward, and at 15 wk postoperation their average MAP [173 +/- 7 mmHg (SE)] was significantly lower vs. sham-lesioned SHR (201 +/- 4 mmHg). In the second experiment, food intake, and hence body weight, among the lesioned and sham-lesioned rats was equalized. Average MAP in the lesioned SHR at 7 and 15 wk postoperation was not different vs. sham-lesioned SHR but was significantly higher (191 +/- 6 mmHg) vs. sham-lesioned SHR but was significantly higher (191 +/- 6 mmHg) vs. sham-lesioned SHR (164 +/- 5 mmHg) 22 wk postoperation. These results indicate that destruction of neuronal perikarya in the ACe in young SHR merely delays the development of hypertension, due to a reduced weight gain. PMID- 7771577 TI - Fish muscle energy metabolism measured during hypoxia and recovery: an in vivo 31P-NMR study. AB - Three fish species were exposed to graded hypoxia levels and allowed to recover. Levels of high-energy phosphate compounds in epaxial white muscle were monitored by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Furthermore, O2 consumption of the animals was measured. With increasing hypoxia load, metabolic parameters started to change in the following order: phosphocreatine (PCr)-to-Pi ratio (decrease), O2 consumption (decrease), [PCr] (decrease), intracellular pH (pHi; decrease), Pi (increase), free ADP concentration ([ADP]free; increase), [ATP] (decrease). PCr levels fell with the PO2. After each increment, the [PCr] reached a stable plateau value while, in some cases, a recovery was observed. This recovery could be explained because the balance between anaerobic and aerobic metabolism is continuously fluctuating during hypoxia as a consequence of changes in the activity of the fish. Consequently the [ADP]free are fluctuating, resulting in an activation of the creatine kinase reaction and the anaerobic glycolysis. In all three species, anaerobic glycolysis was activated, but in contrast to anoxia exposure, metabolic suppression was absent. The changes of [ADP]free and [H+] (which influences the position of the creatine kinase equilibrium) are species dependent. Species differences observed in the other parameters were small. It is concluded that the pattern of the activation of anaerobic metabolism under deep hypoxia is different from that under anoxia. PMID- 7771578 TI - Low-frequency subthreshold sympathetic stimulation augments maximal reflex parasympathetic salivary secretion in cats. AB - Electrical stimulation of the peripheral cut end of the cervical sympathetic trunk for 3 min at frequencies < 1 Hz with pulses of 2-ms duration at supramaximal intensities did not elicit any salivary secretion, but an increase of stimulus frequency over the range 2-10 Hz produced progressively greater salivary secretion, the maximum volume of salivary secretion being evoked at 10 Hz. Frequency-dependent augmentation of parasympathetic reflex submandibular salivary secretion occurred when the lingual nerve was stimulated during repetitive sympathetic stimulation (at frequencies of 0.1-2 Hz) in our sympathectomized cats. The augmentation was found to be linearly related to sympathetic stimulus frequency (regression line calculated by method of least squares; r = 0.939, P < 0.01). This augmentation was abolished by prior treatment with the beta-adrenoceptor blocking drug propranolol (1 mg/kg, P < 0.01 vs. before propranolol) but not by the alpha-adrenoceptor blocking agent phentolamine (1 mg/kg), indicating that the augmented response was mediated via an activation of beta-adrenoceptors. The reduction of the augmentation caused by propranolol had diminished 1 h after its administration, showing that the effect was reversible. PMID- 7771579 TI - Effects of clonidine and yohimbine on parasympathetic reflex salivation and vasodilatation in cat SMG. AB - The present experiments were designed to examine the site of action of the alpha 2-adrenoceptor agonist, clonidine, and the alpha 2-antagonist, yohimbine, on the salivary secretion response to parasympathetic and sympathetic stimulation in the cat submandibular gland (SMG). The parasympathetic reflex salivary secretion was significantly affected by both clonidine and yohimbine (clonidine reduced and yohimbine increased the amount of saliva secreted) while the reflex vasodilator response was not affected by either agent. No degree of methacholine-induced salivation was affected by prior treatment with either clonidine or yohimbine. The salivation elicited by facial nerve root stimulation was markedly reduced by clonidine but potentiated by yohimbine. Prior treatment with scopolamine completely abolished the salivary secretion induced by either methacholine or facial nerve root stimulation. Clonidine and yohimbine had no effect on SMG salivation elicited by sympathetic stimulation. These results indicate that the alpha 2-agonist and antagonist act specifically on parasympathetic salivary fibers but have no effect on parasympathetic vasodilator fibers. They thus suggest that postganglionic parasympathetic innervation is differentiated into salivary and vasodilator fibers. PMID- 7771580 TI - Serotonin3 antagonists block aversion to saccharin in an amino acid-imbalanced diet. AB - Conditioned taste aversion presumably plays a role in the anorectic responses to amino acid-imbalanced diets that induce acute amino acid deficiency. The serotonin3 (5-HT3) receptor antagonists, tropisetron (Trop), MDL-72222 (MDL), and ondansetron, increase intake of imbalanced amino acid diets. Therefore, we tested whether 5-HT3 receptor antagonists would block an aversion to powdered saccharin after it was included in an amino acid-imbalanced diet. Rats were given an intraperitoneal injection of Trop, MDL, or vehicle (Veh), just before introducing one of four diets: imbalanced amino acid diet +/- saccharin (Imb or ImbSac) or a balanced (corrected) diet +/- saccharin (Cor or CorSac). Subsequent aversion to saccharin was shown in preference tests using Cor and CorSac. Saccharin preference was significantly decreased (8.3% on test day 1) in the Veh/ImbSac group, but the Trop/ImbSac group's saccharin preference (57.8%) was similar to controls (49.6-70.3%); MDL also blocked the aversion to saccharin after ImbSac. This confirms previous reports of conditioned taste aversions with amino acid limitation and suggests a role for the 5-HT3 receptor in the development of these aversions. PMID- 7771581 TI - Glucocorticoids and insulin: complex interaction on brown adipose tissue. AB - Glucocorticoids and insulin effect long-term reciprocal changes in food intake and body weight. We tested the interactions of corticosterone and insulin on caloric efficiency, white adipose tissue (WAT) stores, and brown adipose tissue (BAT). Two experiments were performed: 1) adrenalectomized rats were treated with corticosterone with or without streptozotocin-induced diabetes and 2) adrenalectomized, corticosterone-treated, diabetic rats were treated with insulin. By 4-5 days later, > or = 50% of the variance in caloric efficiency, plasma triglycerides, and WAT stores was explained by regression of these variables on corticosterone (catabolic) and insulin (anabolic). When the ratio of the hormones was normal, but concentrations high, overall gain of energy stores decreased and energy was redistributed to fat. Both hormones were anabolic on BAT lipid storage; the hormones played a complex role in the regulation of uncoupling protein (UCP) in BAT. Although corticosterone inhibited and insulin stimulated UCP, these effects were only evident in diabetics and with normoglycemia, respectively. For BAT variables, < or = 50% of the variance was explained by regression on corticosterone and insulin, suggesting that the effects of these hormones are mediated through an intermediate such as sympathetic nervous system input to BAT. PMID- 7771582 TI - Vasoconstrictors alter oxygen, lactate, and glycerol metabolism in the perfused hindlimb of a rat kangaroo. AB - The Tasmanian bettong (Bettongia gaimardi) is a small marsupial rat kangaroo without detectable brown adipose tissue (BAT). The hindlimb was perfused with constant flow at 25 degrees C after cannulation under anesthesia of the femoral artery and vein to one hindlimb. Norepinephrine (NE, 25 nM-2.5 microM) and vasopressin (VP, 10 nM-0.1 microM) each increased perfusion pressure, oxygen consumption (VO2), and lactate and glycerol efflux of the perfused hindlimb. NE mediated increases in VO2 and the efflux of lactate and glycerol were unaffected by propranolol (10 microM) but were completely blocked by the further addition of phentolamine (10 microM). In contrast, serotonin (5-HT; 0.1-2.5 microM) inhibited VO2 and inhibited lactate efflux. The changes induced by NE, VP, and 5-HT were all rapidly reversed by nitroprusside. These results suggest that resting thermogenesis in bettong hindlimb can be differentially controlled by the vasculature, which may also contribute to the induced VO2. This vascular control of skeletal muscle VO2 appears widespread in homeotherm evolution. PMID- 7771583 TI - Control of gill filament blood flow by serotonin in the rainbow trout, Oncorhynchus mykiss. AB - The effects of exogenously applied serotonin [5-hydroxytryptamine (5-HT)] on the distal arterial vasculature of gill filaments were observed using an epi illumination microscope equipped with a water-immersion objective and connected to a video camera. In addition, ventral aortic flow (Q) and celiac artery pressure (PCA) were measured. Intra-arterial injection of serotonin (100 nmol/kg) completely stopped the blood flow in the distal part of the filaments and caused a rapid decrease of PCA. Repeatedly, the flow reduction was found to coincide with a constriction of the distal portion of the efferent filamental vasculature. Because there was no concomitant reduction in Q, it is concluded that a redistribution of blood to more proximal parts of the filaments occurred. After treatment with the serotonergic receptor antagonist methysergide, the vasoconstrictor effect of serotonin on the filamental vasculature was eliminated, while a decrease in PCA was still observed. The results demonstrate a specific site(s) for the serotonergic vasoconstriction in the distal portion of the filament. PMID- 7771585 TI - Kinetic studies and production rate of melatonin in pony mares. AB - The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administration was consistently low (< or = 10%). The hourly melatonin production rates during short (36 +/- 33.6 ng.kg-1.h-1) and long nights (42 +/- 24.0 ng.kg-1.h-1) were not significantly different. It is concluded that the oral dose of exogenous melatonin required to control reproductive pattern in horses would need to be 10 times higher than the nocturnal melatonin production (0.5 microgram/kg) to obtain a physiological plasma melatonin concentration. PMID- 7771584 TI - Sympathoexcitatory influence of a fast conducting raphe-spinal pathway in the rat. AB - Experiments were carried out on 20 pentobarbitone sodium (alpha-chloralose supplemented)-anesthetized, artificially ventilated, and paralyzed rats. The possibility was explored that raphe-spinal neurons with myelinated axons arising in the rostral part of raphe obscurus provide excitatory drive to sympathetic neurons. Electrical stimulation within obscurus was observed to evoke an "early" sympathoexcitatory response compatible with its conduction over such a pathway. The effect of the microinjection of excitatory and inhibitory amino acids [DL homocysteic acid (DLH) and gamma-aminobutyric acid (GABA), respectively] on the evoked response was studied at the sites of electrical stimulation. The size of the early response was increased by 91.7 +/- 24.4% (n = 7) and depressed by -48 +/- 4.8% (n = 7) by DLH and GABA, respectively. Saline was without effect (-14.5 +/- 12.2%, n = 6). The evoked responses were decreased when blood pressure was raised by administration of phenylephrine (2-6 micrograms/kg iv) and totally suppressed by an increase in blood pressure of 19.3 +/- 4.3 mmHg (baseline 89.1 +/- 2.5 mmHg, n = 7). It is concluded that some cell bodies located in rostral raphe obscurus that project to the spinal cord relay excitatory drive to sympathetic neurons. PMID- 7771587 TI - Physiological correlates of vagal nerve innervation in lower vertebrates. AB - In lower vertebrates, cardiac vagal innervation shows less anatomic complexity and specialization than in mammals. To assess the physiological development of vagal specialization in the vertebrates, we investigated cardiac chronotropic effects of electrical stimulation of left and right vagus nerves separately and the interactions between both nerves in anesthetized animals from three vertebrate groups, toad (Bufo marinus), shark (Heterodontus portusjacksoni), and lizard (Physignathus lesueurii). Atropine-sensitive slowing was effected equally by left or right vagi in all species, and chronotropic effects of simultaneous stimulation were the same as the sum of left and right responses. In sharks and lizards, no slowing after atropine was detected (10 Hz stimulation). In toads, after atropine, cardiac slowing was elicited equally by left or right vagal stimulation > 2 Hz. Simultaneous stimulation of both vagi after atropine caused significantly greater slowing than the sum of left and right responses. The results suggest even distribution of left and right vagal nerve endings to pacemaker cells, and limited competition for cardiac receptor sites in lower vertebrates. PMID- 7771586 TI - Central effect of angiotensin III on caudal hypoglossal neurons in rats. AB - We communicated the central effect of angiotensin III (ANG III), a potent signal for extracellular dehydration, on single neurons in the caudal hypoglossal nucleus of Sprague-Dawley rats anesthetized with pentobarbital sodium. A significant number (121 of 168) of caudal hypoglossal neurons responded to intracerebroventricular application of ANG III (80 or 160 pmol), with either an increase (n = 83) or decrease (n = 38) in their spontaneous discharge. These effects of ANG III were significantly reversed by intracerebroventricular application of the nonpeptide angiotensin AT1 receptor antagonist losartan (40 nmol), but not by the AT2 antagonist, PD-123319. The hypoglossal neuronal responses to repeated administration of ANG III (80 pmol), delivered at an interval < or = 18 min, exhibited acute tachyphylaxis. Intracerebroventricular administration of the cholinergic dipsogen, carbachol (50 ng), or the osmotic stimulant, hypertonic saline (0.5 M), also elicited responses in ANG III responsive hypoglossal neurons. These results suggest that neurons in the caudal hypoglossal nucleus may serve as the final common pathway for extracellular and, possibly, intracellular thirst in the rat. Furthermore, it is likely that the action of ANG III is mediated by the AT1 subtype of angiotensin receptors. PMID- 7771588 TI - Effect of total body core cooling during poly I:C-induced fever in rabbits. AB - At ambient temperature (Ta) 20 and 10 degrees C, metabolic heat production and hypothalamic temperature (Thypo) were measured to determine the fever response in six rabbits injected with polyriboinosinic-polyribocytidylic acid (poly I:C; 5 mg/kg iv). Similar measurements were made in afebrile and febrile animals subjected to 3 h of body cooling, in which heat was extracted with a chronically implanted intravascular heat exchanger in a ramplike manner. The fever time course showed a biphasic pattern. During cooling in the febrile experiments, Thypo remained constant or even slightly increased during the time corresponding to the first phase of fever but rapidly fell during the second phase because of a depressed shivering response. The net effect at the end of the cooling period was that Thypo decreased by 0.4 and 0.6 degree C more than in the afebrile cooling experiments at Ta 20 and 10 degrees C, respectively. The results indicate normal shivering responses during phase I of poly I:C-induced fever and depressed shivering in phase I, possibly because of a reduced thermosensitivity. PMID- 7771589 TI - Poly I:C-induced fever elevates threshold for shivering but reduces thermosensitivity in rabbits. AB - Shivering threshold and thermosensitivity were determined in six conscious rabbits at ambient temperature (Ta) 20 and 10 degrees C before and at six different times after saline injection (0.15 ml iv) and polyriboinosinic polyribocytidylic acid (poly I:C)-induced fever (5 micrograms/kg iv). Thermosensitivity was calculated by regression of metabolic heat production (M) and hypothalamic temperature (Thypo) during short periods (5-10 min) of square wave cooling. Heat was extracted with a chronically implanted intravascular heat exchanger. Shivering threshold was calculated as the Thypo at which the thermosensitivity line crossed resting M as measured in afebrile animals at Ta 20 degrees C. There were negligible changes in shivering threshold and thermosensitivity in saline-injected rabbits. In the febrile animals, shivering threshold generally followed the shape of the biphasic fever response. At Ta 20 degrees C, shivering threshold was higher than regulated Thypo during the initial rising phase of fever and was lower during recovery. At Ta 10 degrees C the shivering thresholds were always higher than regulated Thypo except during recovery. Thermosensitivity was reduced by 30-41% during fever. PMID- 7771590 TI - Cardiovascular effects of arginine vasotocin, atrial natriuretic peptide, and epinephrine in freshwater eels. AB - The effects of 150 ng/kg iv injections of arginine vasotocin (AVT), eel atrial natriuretic peptide (ANP), and epinephrine (Epi) on the cardiovascular dynamics of resting freshwater eels, Anguilla rostrata were studied. Injection of AVT into the caudal vein significantly increased cardiac output (CO) from 15.3 to 23.6 ml.min-1.kg-1 primarily by increasing stroke volume. Mean dorsal aortic pressure (PDA) also increased. Estimated branchial shunting (2.54 ml.min-1.kg-1) was elevated by 130% because of an increased proportion of CO, indicating a vasoconstriction of the branchial arterioarterial pathway. In contrast, Epi reduced the fraction of CO perfusing the arteriovenous pathway. Epi also produced a positive chronotropic effect, increased CO and systemic vasoconstriction, resulting in a vasopressor response. These changes occurred earlier than those of AVT and ANP. Pressor responses triggered by AVT and Epi preceded the increases in CO. Injections of 150 and 200 ng/kg ANP caused a reduction in PDA due to a decrease in CO (and SV) but failed to modulate systemic resistance. The change in CO was the primary contributor to the pressor (and depressor) responses elicited by the three hormones. PMID- 7771591 TI - Chemical sympathectomy and maternal separation affect neonatal stress responses and adrenal sensitivity to ACTH. AB - The participation of sympathetic adrenal innervation in the control of the neonatal adrenocortical system and in changes in adrenal sensitivity after maternal separation for 24 h was tested in 10- and 23-day-old pups. Chemical sympathectomy by guanethidine (20 mg/kg body wt) decreased basal and stimulated corticosterone compound B (B) secretion without affecting adrenocorticotropic hormone (ACTH) release, abolished the enhanced adrenal sensitivity to ACTH induced by maternal separation in 10-day-old pups, but did not modify adrenal sensitivity following ether stress in 23-day-old pups. Guanethidine treatment did not affect body and adrenal weight or adrenal choline acetyltransferase activity, but it increased tyrosine hydroxylase activity at both ages. Both chronic guanethidine treatment and acute corticotropin-releasing factor immunoneutralization reduced plasma B levels after maternal separation without affecting plasma ACTH levels. Maternal separation in 10-day-old pups enhanced basal and stimulated ACTH and B secretion after exposure to ether vapors and insulin-induced hypoglycemia (IIH). In nonseparated pups, IIH did not stimulate ACTH secretion and caused small increases in B secretion; however, the enhanced response of separated pups to IIH was due to the effects of intraperitoneal injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771592 TI - Responses of the circulatory system and muscle sympathetic nerve activity to head down tilt in humans. AB - These experiments were conducted to examine whether changes in central and peripheral hemodynamics were proportional to muscle sympathetic nerve activity (MSNA) during graded head-down tilt (HDT). Twelve healthy males (19-42 yr old) underwent HDT at 15 degrees and 30 degrees for 10 min each with a 10-min rest period between the trials. MSNA at 15 degrees HDT declined by 31 +/- 5% (P < 0.05) for burst rate and by 37 +/- 3% (P < 0.05) for total activity. At 30 degrees HDT, the reduction in MSNA was 51 +/- 5% for burst rate (P < 0.05 vs. 15 degrees HDT) and 46 +/- 5% for total activity (P < 0.05 vs. 15 degrees HDT). Stroke volume increased (P < 0.05) during both 15 degrees and 30 degrees HDT, but heart rate and blood pressure remained unchanged. A concurrent increase in central venous pressure (P < 0.05) and stroke volume with a reduction of thoracic impedance (P < 0.05) suggests that both pressure and volume in the atrium were elevated during HDT, and the magnitude of these changes was greater (P < 0.05) at 30 degrees HDT than at 15 degrees HDT. Forearm blood flow increased during HDT at both 15 degrees and 30 degrees, and the magnitude of the increase was greater (P < 0.05) at 30 degrees HDT. It is concluded that the magnitude of the loading of the cardiopulmonary mechanoreceptors during HDT was higher at 30 degrees in comparison to 15 degrees. This increased the afferent firing rate by the cardiopulmonary receptors and probably inhibited sympathetic outflow in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771593 TI - Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus. AB - Microinjection of glutamate into sites within the medullary raphe nuclei (pallidus and obscurus) at levels caudal to the obex resulted in a dose-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate in anesthetized rabbits. The depressor and sympathoinhibitory responses were similar in magnitude to those elicited from the previously described depressor region in the caudal ventrolateral medulla (CVLM) but had a shorter duration, in both intact and barodenervated animals. The bradycardia was not altered by barodenervation but was reduced after administration of propranolol or atropine and abolished after administration of both drugs. The neuroinhibitory compounds gamma-aminobutyric acid or muscimol had no effect on MAP or RSNA when injected into the caudal medullary raphe nuclei but evoked a pressor and sympathoexcitatory response when injected into the CVLM. The results indicate that neurons within the caudal raphe pallidus and obscurus can powerfully inhibit sympathetic activity, but unlike sympathoinhibitory neurons in the CVLM, they are not tonically active and are not capable of producing sustained changes in arterial pressure and sympathetic activity. PMID- 7771594 TI - Seasonal influences on the control of plasma sex hormone-binding globulin by T4 in male little brown bats. AB - Male little brown bats showed a well-defined seasonal cycle of plasma thyroxine (T4). Total T4 concentrations increased during hibernation, reached peak levels in May at spring emergence, and subsequently declined to lowest levels in September. Thyroxine-binding globulin (TBG) activity increased only in summer, and seasonal changes in non-TBG-bound T4 generally paralleled those of total T4. During the fall and early hibernation period, bats studied under feral conditions or following photoperiod manipulation showed coincident changes in plasma T4 and sex hormone-binding globulin (SHBG) levels. In contrast, males studied during late hibernation or following spring arousal exhibited declining plasma T4 levels during periods of increased SHBG activity. Additionally, the prehibernation decline in SHBG did not depend on changing environmental conditions. Bats maintained under summerlike conditions during the fall showed normal seasonal reductions in SHBG and T4. These studies indicate that T4 is the likely physiological regulator of plasma SHBG activity during the fall and early hibernation, but that other factors modulate the timing of SHBG induction in the spring. PMID- 7771595 TI - Lipopolysaccharide increases EEG delta activity within non-REM sleep and disrupts sleep continuity in rats. AB - Activation of the immune system by microorganisms or specific microbial constituents promotes non-rapid-eye-movement (REM) sleep (non-REMS). In this study, we assessed the effects of lipopolysaccharide (LPS) on sleep duration, electroencephalogram (EEG) power spectra, and brain temperature (Tbr) in rats. Twenty-four hour recordings were made before and after intraperitoneal injection of vehicle or 30 or 100 micrograms/kg LPS at lights on. During the first 12 h after administration of both doses of LPS, Tbr was elevated, REMS duration was reduced, and non-REMS duration was unchanged, whereas the non-REMS episodes were shortened. EEG activity within non-REMS from 0.5 to 7 Hz was enhanced during hours 3-12. During the second 12-h period, the number of non-REMS and REMS episodes and the total time in both states were increased. EEG activity within non-REMS was mainly reduced in the entire frequency range (0.5-25.5 Hz). The effects of LPS did not differ between the doses. The effects of LPS on EEG power spectra are similar to those observed after sleep deprivation, i.e., a physiological intensification of non-REMS, indicating that both manipulations may activate common sleep EEG regulatory mechanisms. However, the disruption of non REMS continuity following LPS administration at light onset contrasts the changes induced by sleep deprivation and may reflect an effect of a systemic inflammatory response on sleep maintenance. PMID- 7771596 TI - Regulation of neurohypophysial hormone secretion in an Australian marsupial. AB - The brushtail possum secretes the typically reptilian mesotocin (MT) and arginine vasopressin (AVP) as its neurohypophysial hormones. In this study we have looked at the regulation of MT and AVP secretion in conscious possums by studying the effects of surgical stress and handling of animals, hypertonic saline infusion, hemorrhage, and angiotensin II (ANG II) infusion on the plasma concentrations of MT and AVP. Surgical insertion of a jugular catheter and handling stress increased MT secretion for 3 days after surgery without affecting plasma AVP concentrations. Hypertonic saline infusion induced a gradual increase in plasma osmolarity and Na+ concentration throughout the infusion, which steadily increased plasma AVP without affecting plasma K+ or hematocrit. The relationship between plasma osmolarity and AVP was exponential. Plasma MT was stimulated only by supraphysiological plasma osmolarities. ANG II increased plasma MT and AVP concentrations equipotently throughout the infusion. Hemorrhage was a relatively specific stimulus for AVP secretion, but MT secretion was highly stimulated during severe hypovolemia. It was concluded that MT and AVP secretion is differentially regulated in the possum. PMID- 7771597 TI - Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS. AB - To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain. PMID- 7771598 TI - Upregulation of the GABAA/benzodiazepine receptor during anoxia in the freshwater turtle brain. AB - The freshwater turtle brain survives anoxia by decreasing its energy expenditure. During this anoxic period there is a sustained release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This study investigated whether there was a corresponding change in the binding properties of the GABAA/benzodiazepine (GABA/BDZ) receptor. Turtles (Trachemys scripta) were subjected to a 100% N2 atmosphere for up to 24 h. After exposure, the cerebral cortex was dissected out, and saturation binding assays for GABA/BDZ receptors were performed using the radioligand [3H]flunitrazepam. Control turtles had a dissociation constant (Kd) of 1.97 +/- 0.54 nM and a receptor density (Bmax) of 2,404 +/- 221 fmol/mg protein. The Kd showed no significant change over 24 h of anoxia. However, significant increases were seen in Bmax after 12 h (21%, P < 0.05) and 24 h (29%, P < 0.01) of anoxia. We suggest that a long-term upregulation of GABAA receptors occurs in the anoxic turtle brain that acts to increase the inhibitory effectiveness of the released GABA and thereby contributes to anoxia survival of the turtle. PMID- 7771599 TI - Rat vasopressin cell responses to simulated hemorrhage: stimulus-dependent role for A1 noradrenergic neurons. AB - c-fos expression mapping and electrophysiological recording experiments were done to clarify the role of the A1 noradrenergic cell group in the vasopressin response to hypotensive hemorrhage. In pentobarbital-anesthetized rats, moderate and severe hypotensive hemorrhages were simulated by brief occlusion of the inferior vena cava sufficient to reduce mean arterial pressure to approximately 50 or 30 mmHg, respectively. Both stimuli significantly increased the number of A1 region catecholamine cells displaying Fos-like immunoreactivity, this effect being most prominent at the level of the area postrema. Both stimuli also increased the number of supraoptic nucleus vasopressin cells displaying Fos-like immunoreactivity. Accordingly, electrophysiological studies involving separate animals confirmed that both moderate and severe caval occlusion significantly increased the firing of functionally identified vasopressin cells recorded in the supraoptic nucleus. However, although interruption of A1 region neuronal function by injection of gamma-aminobutyric acid at the level of the area postrema eliminated the increase in vasopressin cell firing elicited by moderate caval occlusion, it did not block the response to severe caval occlusion. These findings suggest that, in the rat, the vasopressin response to an acute reduction in central blood volume, such as that produced by hemorrhage, depends on the A1 projection only if the stimulus is of moderate intensity. Severe stimuli appear to involve activation of both the A1 projection and an additional vasopressin stimulatory pathway that bypasses the A1 region. PMID- 7771600 TI - The effectiveness of insecticide-impregnated bed nets in reducing cases of malaria infection: a meta-analysis of published results. AB - The use of insecticide-impregnated bed nets to minimize human-vector contact may reduce the incidence of malaria. Consequently, several field trials have evaluated their effectiveness as a malaria prevention strategy. A meta-analysis of published reports of field trials that measured the incidence of infections was performed to provide a measure of the effectiveness of insecticide-treated bed nets in preventing clinical malaria. Subsetted analyses were performed on the 10 field trials to calculate pooled incidence rate ratios of infection among the study groups. For the studies comparing insecticide-impregnated bed nets with untreated bed nets, the summary incidence rate ratio for acquiring malarial infections was 0.757 (95% confidence interval [CI] = 0.612-0.938), representing a reduction of 24%. For the studies comparing permethrin-impregnated bed nets with controls without bed nets, the summary incidence rate ratio was 0.497 (95% CI = 0.417-0.592) (Rothman-Boice heterogeneity statistics = 17.27 [P = 0.004] and 23.55 [P = 0.0003], respectively). These data suggest that insecticide impregnated bed nets are effective in preventing malaria, decreasing the incidence rate ratio by approximately 50% in field trials performed to date. PMID- 7771601 TI - Knowledge, beliefs, and practices in relation to malaria transmission and vector control in Guatemala. AB - As part of an effort to involve community members in malaria control activities, we studied knowledge, beliefs, and practices of residents of both the Pacific coastal plain and northeastern Guatemala related to malaria transmission and Anopheles albimanus control. Most residents recognized the role of mosquitoes in malaria transmission, but few knew how mosquitoes acquired their infections or understood the risk of having an untreated person in their midst. If this were more widely known, residents might put greater pressure on infected patients to seek timely and appropriate antimalarial treatment. Seventy-three percent of families owned one or more bed nets; however, even though most informants believed that bed nets help protect against malaria, the major reason for using them was to prevent nuisance mosquito bites. It is concluded that efforts should be made to promote bed net use by seeking ways to make them more affordable and by emphasizing their effectiveness as a barrier to nuisance mosquitoes. Although residents have a very positive opinion of the National Malaria Service spray teams, it is proposed that cooperation might be improved if malaria workers would emphasize the fact that house spraying reduces the numbers of nuisance mosquitoes and other pest insects, rather than focusing solely on malaria prevention, which most informants believed was less important. This study emphasizes the importance of understanding community beliefs and practices when planning or evaluating vector control activities. PMID- 7771603 TI - A household-based, case-control study of environmental factors associated with hantavirus pulmonary syndrome in the southwestern United States. AB - During an outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States, trained environmental assessment teams conducted surveys at 17 case-patient homes and matched controls from June through August 1993. Variables related to rodent abundance were quantified and standardized rodent trapping was conducted around and within households. The majority of households were located in pinon-juniper vegetation zones, and there were no significant differences in the type of house in which cases and controls lived. The only environmental factor that distinguished case households from controls was significantly higher small rodent densities (median trap success for case sites = 17.3%, 12.7% for near controls, and 8.3% for far controls). Frequency of hantaviral infection in deer mice (Peromyscus maniculatus) did not vary significantly among households of cases and controls, with a range of 27.5-32.5% antibody-positive. Indices of rodent fecal contamination were slightly higher in case houses. The data indicate that higher rodent densities were associated with households in which HPS cases occurred. Strategies that control rodent numbers and decrease rodent access to dwellings may reduce risk of human infection. PMID- 7771602 TI - Short report: a placebo-controlled study of Lactobacillus GG colonization in one to-three-year-old Peruvian children. AB - A pilot, placebo-controlled study conducted in Peruvian toddlers in a periurban shanty-town community demonstrates that 1) a simple fluorescent antibody test performed on bacteria from colonies grown on solid culture media can be used as a presumptive screening tool for Lactobacillus GG, 2) Lactobacillus GG powder sprinkled on flavored gelatin as a nutritional supplement is well-accepted by infants and mothers in this population, and 3) daily doses of Lactobacillus GG result in efficient colonization of the gastrointestinal tract of Peruvian infants. This study demonstrates that Lactobacillus GG should be evaluated as an adjunct for diarrhea control programs at the community level as well as in hospital-based settings. PMID- 7771604 TI - Hepatitis B virus infection on a tropical island: sociodemographic and geographic risk factors in Guadeloupe. AB - A seroepidemiologic study on a cross-sectional sample of blood donors was carried out in Guadeloupe, a French West Indies island, to estimate the prevalence of hepatitis B virus (HBV) markers, and to investigate the influence of age, socioeconomic, and geographic factors on prior HBV infection. Blood specimens and sociodemographic data were collected in 1989 from 2,339 blood donors residing on the island. A total of 73 (3.1%) of 2,339 were found to be HBV surface antigen carriers, and 518 (22.1%) were positive for antibody to HBV core antigen. Among them, 61 were positive for both markers and consequently 530 persons (22.7%) were considered to have evidence of prior HBV infection. Multivariate logistic regression analyses identified age and low socioprofessional status as being related to HBV infection, as in many endemic areas. In addition, some major geographic risk factors were highlighted, reflecting a strongly hyperendemic situation in specific areas and the potential influence of horizontal transmission or unknown environmental factors on these particular populations. PMID- 7771605 TI - Short report: Rift Valley fever in western Africa: isolations from Aedes mosquitoes during an interepizootic period. AB - Thirteen strains of Rift Valley fever virus were isolated from Aedes vexans and Ae. ochraceus mosquitoes collected in October and November 1993 in northern Senegal. Entomologic and serologic data show that the risk of a new epizootic is increasing in this region. PMID- 7771606 TI - National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome. AB - Between 1981 and 1992, the Centers for Disease Control collected and summarized 9,223 cases of Rocky Mountain spotted fever (RMSF) reported from 46 states. Four states (North Carolina, Oklahoma, Tennessee, and South Carolina) accounted for 48% of the reports. The annual incidence per million U.S. population decreased from a high in 1981 of 5.2 to a low in 1992 of 2.0, primarily due to decreased incidence in the southeast. Case report forms were filed on 7,650 patients, of whom 4,217 had laboratory-confirmed RMSF. The age group with the highest incidence was those 5-9 years of age. Most cases (90.0%) occurred between April 1 and September 30 and included a history of tick attachment (59.6%). Reported symptoms included fever (94.0%), headache (86.2%), myalgia (82.5%), and rash (80.2%). The case-fatality ratio was 4.0%. Risk factors associated with death included older age, delay in treatment or no treatment, and treatment with chloramphenicol (compared with tetracycline); however, insufficient data existed to fully assess the confounding effect of severity of illness on antibiotic choice. PMID- 7771607 TI - A space-occupying lesion in the liver due to Capillaria infection. AB - A space-occupying lesion 3.5 by 2.0 cm in size caused by Capillaria infection was revealed ultrasonographically in segment 6 (S6) of the liver of a 32-year-old woman from Okinawa, Japan, who was hospitalized with a complaint of pain in the right upper quadrant. Laboratory examination showed leukocytosis of 10,400/mm3 with 22% eosinophils and slight impairment of liver function. The tumor was removed surgically and found to be a necrotic granuloma with eosinophilic infiltration formed around a degenerated nematode. The causative agent was presumed to be Capillaria hepatica based on the morphology of the bacillary bands and stichosome observed in the sectioned worm and in the fragments of worm recovered by dissecting the tumor tissue that was embedded in paraffin. PMID- 7771608 TI - Prevention of thromboses in human patients with Bothrops lanceolatus envenoming in Martinique: failure of anticoagulants and efficacy of a monospecific antivenom. Research Group on Snake Bites in Martinique. AB - Envenomation by the Bothrops lanceolatus, a snake found only in Martinique, leads to swelling and pain, and occasionally to systemic signs and/or coagulopathy. Severe thromboses at some distance from the site of the bite may appear within 48 hr. Uncertainties as to the actual development of thrombotic complications in patients appearing to be suffering from moderate poisoning and as to the availability and the toxicity of a monospecific antivenom (AVS) initially led us to reserve antivenom for the most severe cases, and to use anticoagulants to prevent thromboses in all patients. This approach was modified after we observed serious thromboses in patients with moderate poisoning. Of 50 adult snake bite cases hospitalized between June 1991 and August 1994, 11 developed serious thrombotic complications at 36 /+- 27 hr (mean +/- SD) (range 12-96) following envenomation, despite early preventive anticoagulant therapy. Those included pulmonary embolism (two cases), cerebral infarction (six cases), myocardial infarction (one case), and cerebral and myocardial infarctions (two cases). Sixteen patients were not treated with AVS: 10 of these recovered without complications and six developed systemic thrombosis causing permanent disability in three cases. Thirty were treated with an intravenous infusion of 2-6 vials of AVS given 2-48 hr after the bite. Of these, three died of cerebral infarction that developed before the initiation of serotherapy. All others recovered. Among patients treated with AVS, three presented with mild anaphylactic reactions, while one developed serum sickness that responded to steroids. These data indicate that preventive anticoagulant therapy is of limited efficacy in Martinique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771609 TI - Effect of semiannual treatments of ivermectin on the prevalence and intensity of Onchocerca volvulus skin infection, ocular lesions, and infectivity of Simulium ochraceum populations in southern Mexico. AB - The effect of semiannual ivermectin treatment along with nodulectomy on filarial transmission levels were estimated during the three dry seasons of 1991-1993 in a hyperendemic village in southern Mexico. Parasitologic and ophthalmologic examinations were carried out every six months until five drug treatments were completed. Ivermectin mass treatment with a coverage of approximately 80% had a significant impact (P < 0.05) on the prevalence of skin infection and the mean microfilarial skin density (CMFL), which were reduced 38% and 89%, respectively. A gradual and significant (P < 0.05) decrease in the mean microfilariae number in the anterior chamber of the eye and in corneal opacities was also observed as the CMFL was reduced. After three treatments, these were reduced 84% and 69%, respectively. However, after two years of continuous intervention, no significant differences (P > 0.05) were observed in either the daily mean infective biting density and the daily mean transmission potential. This was probably due to the remaining microfilarial load provided by the untreated resident population and migrant groups. On the whole, our results confirm both the efficacy of ivermectin to alleviate the clinical manifestations of the disease and its minimal impact on Onchocerca volvulus transmission, and indicate the need both to achieve higher levels of drug coverage and to incorporate other measures to stop transmission until a macrofilaricide drug is found. PMID- 7771610 TI - Antimony oxidation states in antileishmanial drugs. AB - Chemical methods specific for the determination of the levels of trivalent antimony (Sb+3) and pentavalent antimony (Sb+5) were used to investigate proprietary formulas used to treat leishmaniasis. Trivalent antimony was determined by differential pulse polarography, whereas Sb+5 was determined by iodine titration. Proprietary formulas based on N-meglumine antimoniate (Glucantime) were analyzed in detail. The results showed Sb+3 in all ampules of Glucantime. In formulations said to contain either 85 or 100 mg of Sb+5/ml, we found both forms of antimony. The amount of Sb+3 ranged from 10.5 to 15.8% (10.06 18.96 mg of Sb/ml). These findings raise issues on product stability and standardization and may help to clarify resistance to antimonial drugs and the reducing effect of tissue on Sb+5. PMID- 7771611 TI - The pathology of cutaneous leishmaniasis due to Leishmania major in Sudan. AB - The pathology of cutaneous leishmaniasis in Sudan, where the disease is caused by Leishmania major, was studied by light and electron microscopy. Lesions were classified into four distinct groups based on the ratio of different cell types, especially lymphocytes, macrophages, and plasma cells in the inflammatory infiltrate, and the formation of compact epithelioid granulomas or the presence of necrosis. In the lesions, there was a positive correlation between the number of lymphocytes and the number of activated macrophages and epithelioid cells. We suggest that the parasites are eliminated from the lesion by two processes: 1) a lytic mechanism in which parasites are lysed within activated macrophages and 2) necrosis of parasitized macrophages. Morphologic evidence for these two mechanisms of parasite elimination was detected by both light and electron microscopy. The evolution of the pathology of the lesions was followed by rebiopsy when the lesion had regressed in size under antileishmanial therapy. PMID- 7771612 TI - Plasmodium vivax: freeze-fracture studies on the ultrastructure of the sporozoites within the salivary gland of the mosquito Anopheles stephensi. AB - Freeze-fracturing has been used to study the ultrastructure of the sporozoites of the malarial parasite Plasmodium vivax within the salivary gland of the mosquito Anopheles stephensi. The architecture of the pellicular complex of the salivary gland sporozoites was essentially the same as that reported for the intraoocystic forms, but the outline of cross-fractured P. vivax sporozoites was more flattened and crescent shaped as opposed to the circular outline described for the intraoocystic sporozoites. The salivary gland sporozoites of P. vivax also exhibited apical rosettes and a cytosome connected to a food vacuole, two unique structures not previously reported for malarial sporozoites. PMID- 7771613 TI - Transient expression of a promoter-reporter construct in differentiated adult salivary glands and embryos of the mosquito Aedes aegypti. AB - Vector-borne pathogens develop in close association with specific tissues in their insect hosts. Efforts are being made to characterize insect genes that are expressed in tissues that have important roles in pathogen propagation. Successful transfection and expression of exogenous genes in terminally differentiated tissues of insects has previously proven difficult. Here we report a method that should allow the analysis of genes that are expressed in adult tissues and organs. Transient expression assays have been developed using the salivary glands of the mosquito, Aedes aegypti, which can now be used to analyze salivary gland-specific promoter sequences. A liposome-based transfection reagent was used to transfect cultured adult salivary glands with a DNA construct carrying the luciferase reporter gene under the control of the Drosophila melanogaster heat shock 70 promoter. Luciferase activity was detected in glands 18-20 hr post-transfection. This assay can now be used to determine the regulatory activity of other putative promoter sequences from salivary gland specific genes. Alternatively, the assay may be used to study the effect of recombinant gene expression on parasite invasion and development. In addition, transient expression of gene constructs in embryos is shown to be a powerful tool for analyzing genes that are expressed at this stage of the mosquito life cycle. PMID- 7771615 TI - Health care reform: residency training and medical education. PMID- 7771614 TI - Evaluation of the severe combined immunodeficient (SCID) mouse as an animal model for dengue viral infection. AB - Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood lymphocytes (hu-PBL) were evaluated as an animal model for demonstrating dengue (DEN) viral infection. Reconstituted mice (hu-PBL-SCID) that demonstrated successful engraftment by the presence of serum titers of human immunoglobulin (Ig) were inoculated intraperitoneally with DEN virus serotype 1 (DEN-1). Serial blood samples were taken postinoculation and assayed for virus in C6/36 cells. The identity of all viral isolates was confirmed by an immunofluorescence antibody assay using DEN-1 monoclonal antibody. A total of six experiments were performed using different procedures of reconstitution and infection, and in three of these experiments, DEN-1 virus was recovered from the hu-PBL-SCID mice. In the first successful experiment, DEN-1 virus was recovered on postinoculation day (PID) 24 from blood, spleen, thymus, and lung tissues of one of eight hu-PBL SCID mice. A second group of eight hu-PBL-SCID mice were inoculated with human monocytes infected in vitro with DEN-1 virus. Virus was recovered from the blood of mice between PID 15 and 23, and from lung tissue of one of these mice. In a third experiment, seven SCID mice were treated initially with anti-asialo GM1 antibody to eliminate natural killer cells, and then were injected simultaneously with a mixture of hu-PBL and DEN-1 virus. Virus was demonstrated in the blood of one mouse on PID 38, and in another mouse on PID 8, 12, 20, 24, and 36.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771616 TI - Effect of multilevel sequential stenosis on lower extremity arterial duplex scanning. AB - BACKGROUND: The sensitivity of lower extremity arterial duplex scanning in detecting a > 50% stenosis may be decreased in extremities with multilevel sequential stenosis. PATIENTS AND METHODS: The results of lower extremity arterial duplex scanning of the common femoral, upper and lower superficial femoral, above- and below-knee popliteal arteries, and tibioperoneal trunk in 80 extremities of 44 patients were compared to those of arteriography. Thirty-one arterial segments in 27 extremities had a > 50% stenosis. The stenoses were categorized as first order (first or only stenotic segment in the extremity, n = 23) and second order (stenosis occurring distal to a > 50% stenosis, n = 4, or occlusion, n = 4). RESULTS: The sensitivity, specificity, and positive predictive values of duplex scan detection of a > 50% arterial stenosis or occlusion were 86%, 96%, and 67% for the common femoral artery; 95%, 98%, and 95% for the upper superficial femoral artery; 97%, 90%, and 88%, for the lower superficial femoral artery; 84%, 90%, and 87% for the above-knee popliteal artery; 47%, 98%, and 90% for the below-knee popliteal artery; and 25%, 100%, and 100% for the tibioperoneal trunk. Duplex scanning detected 18 (78%) of the 23 first-order stenoses compared to only 1 (13%) of the 8 second-order stenoses in limbs with multilevel sequential disease (P < 0.01). The peak systolic velocity at the stenotic site was significantly higher for first-order (mean +/- SD 168 +/- 54 cm/s) compared to second-order (38 +/- 13 cm/s) stenoses (P < 0.00002). CONCLUSIONS: Duplex scanning was highly sensitive in detecting lower extremity first-order stenoses. Low peak systolic velocities at second-order stenoses of limbs with multilevel sequential disease significantly decreased the sensitivity of duplex scanning. PMID- 7771617 TI - A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. AB - BACKGROUND: Various studies have been performed in general surgery patients comparing low molecular weight heparin (LMWH) with standard heparin (SH) for the prevention of postoperative deep vein thrombosis (DVT), revealing contradicting results. Therefore, we have compared the efficacy and safety of a LMWH for the prevention of DVT after major general surgery. PATIENTS AND METHODS: Patients received either 20 mg LMWH (enoxaparin) once daily, or 5,000 IU SH TID, starting preoperatively in a prospective, randomized, double-blind international multicenter trial. DVT was diagnosed using fibrinogen I 125 leg scanning. Major and minor bleeding were assessed clinically. RESULTS: A total of 718 patients were randomized to LMWH, and 709 patients to SH. DVT was detected in 58 LMWH treated patients (8.1%, 95% confidence interval [CI] 6.2% to 10.3%) and in 45 patients allocated to SH (6.3%, 95% CI 4.7% to 8.4%, P > 0.05). Major bleeding complications occurred in 11 LMWH-treated patients (1.5%, 95% CI 0.8% to 2.7%) and in 18 patients to whom standard heparin was administered (2.5%, 95% CI 1.5% to 3.9%, P > 0.05). Four LMWH-treated patients (0.6%) required reoperation for bleeding as compared to 13 patients in the SH group (1.8%, P = 0.03). CONCLUSION: This LMWH appeared as effective and safe as SH. In view of its more convenient way of administration, this LMWH might be preferred for thromboprophylaxis. PMID- 7771618 TI - Venous hemodynamic abnormalities in patients with leg ulceration. AB - PURPOSE: Venous ulceration in the leg has been predominantly associated with deep venous insufficiency, although a few reports have implicated the superficial veins. The aim of this study was to identify the distribution of valvular incompetence in patients with active leg ulceration. PATIENTS AND METHODS: Color flow duplex imaging (CFDI) ultrasonography was used to evaluate the entire venous system--superficial, perforator and deep--from groin to ankle in 112 limbs of 94 patients with venous leg ulcers. RESULTS: Seventy two limbs (64%) had multisystem incompetence and 36 (32%) had one system involved only, whereas in 4 limbs (4%) there was no venous incompetence. Deep venous reflux exclusively was present in 7 limbs (6%) and the perforator system alone was involved only in 3 limbs (3%). However, isolated superficial incompetence was seen in 26 extremities (23%) and combination of superficial with perforator system alone in 23 (21%). In addition, reflux overall in the superficial system (alone and in combination with perforator and deep systems) was seen in 94 limbs (84%). The most common pattern (28%) of abnormality was reflux in all systems, superficial, perforator, and deep. CONCLUSIONS: The results of this study show that variable combined patterns account for over two thirds of patients with ulceration. No comprehensive surgical policy for alleviating ulceration can be justified; we suggest that a complete evaluation of all venous systems from groin to ankle with CFDI ultrasonography in patients with venous ulceration is practical on a routine basis and will be particularly valuable before surgery in order to target intervention at specific incompetent sites. PMID- 7771619 TI - The natural history of breast cancer with more than 10 positive nodes. AB - BACKGROUND: Experimental protocols are being used increasingly to treat breast cancer with > 10 positive nodes. An appreciation of the natural history of this disease is crucial for choosing the optimal therapeutic approach. PATIENTS AND METHODS: We retrospectively reviewed the records of 141 patients who had breast cancer with > 10 positive nodes and received definitive therapy at our institution in the years 1969 through 1991. Because therapy evolved during this period, we compared the results from 1969 through 1981 to those from 1982 through 1991. RESULTS: Ninety-one patients (65%) were > or = 50 years of age. Fifty-four (38%) were estrogen receptor (ER) positive, the remainder were ER negative or ER status unknown. Fifty-seven (40%) had 10 to 15 positive nodes, 63 (45%) had 16 to 25, and 21 (15%) had > 25. The ratio of positive nodes to total nodes was < 50% in 22 patients, 50% to 75% in 49, and > 75% in 70. One hundred thirty-four patients (95%) underwent modified or radical mastectomy. Forty (28%) received adjuvant chemotherapy, including 16 (11%) of 58 patients treated prior to 1981. Eleven patients (8%) were treated with adjuvant radiation therapy. The median survival for all patients was 52 months, with an actuarial survival of 29% at 10 years. Patients treated after 1981 had significantly improved survival. They lived a median of 68 months postoperatively, as compared to 41 months among patients treated earlier. CONCLUSIONS: This is a high-risk group of patients, yet there is a small subset who can obtain a long survival with standard treatment modalities. PMID- 7771620 TI - The management of splenic artery aneurysms: experience with 23 cases. AB - BACKGROUND: Splenic artery aneurysms (SAA) are rare clinical entities that carry the risk of rupture and fatal hemorrhage. They are being detected with increased frequency and often cause a clinical dilemma, particularly when small lesions occur in compromised patients. This paper relates our experience in the management of SAA over a 14-year period. PATIENTS AND METHODS: We analyzed data from the medical charts and radiological images of all patients diagnosed with SAA at Emory University Hospital from December 1979 to January 1993. RESULTS: A search of medical records discovered 23 patients who experienced 44 SAAs during the time period under study. Twelve patients had multiple SAAs, most of them in the distal third of the artery. Seven had SAAs > 2 cm in diameter. Modalities used to diagnose SAA included Doppler ultrasound in 9 patients, computerized tomography in 10, and arteriography in 21. Sixteen patients had portal hypertension. Splenomegaly was present in 13 of those with portal hypertension. Aneurysm excision and splenectomy were carried out emergently on 2 patients and electively on 1. Aneurysm ligation was performed on 3 patients. One patient underwent embolization of the lesion. Sixteen asymptomatic patients whose aneurysms were < 2 cm in diameter were treated expectantly for a mean period of 3 years. One patient who received active treatment died. There were no documented deaths attributable to SAA among patients treated by observation. Six patients in this group died of unrelated causes. The longest follow-up was 7 years. CONCLUSIONS: We support current criteria that call for active treatment of symptomatic or enlarging SAAs, with particular emphasis on treating women anticipating pregnancy and patients undergoing orthotopic liver transplantations. For most other cases, expectant treatment is acceptable. PMID- 7771622 TI - Criteria for safe hepatic resection. AB - BACKGROUND: To lower morbidity after hepatic resection, the authors examined the influence of predictor variables including: age, sex, preoperative risk factors, serum total bilirubin level, plasma retention rate of indocyanine green at 15 minutes, underlying liver disease, operative blood loss, operation time, amount of whole blood transfused, vascular occlusion time, surgical procedure employed, and extent of hepatic resection. PATIENTS AND METHODS: Between January 1990 and December 1992, 172 patients underwent hepatic resection based on our own criteria for hepatectomy, including the presence or absence of ascites, serum total bilirubin level, and the plasma retention rate of indocyanine green at 15 minutes in patients with chronic liver disease. The morbidity rate was 37.2%, and the hospital and operative mortality rates were 2.3% and 0.6%. RESULTS: The multiple logistic model revealed that the risk of morbidity was increased by longer operation time, major hepatic resection, and preoperative cardiovascular disease. CONCLUSIONS: Shortening the operation time without increasing operative blood loss and further modalities for making major hepatectomy safer are future problems to be addressed. PMID- 7771621 TI - Pancreaticojejunostomy versus controlled pancreaticocutaneous fistula in pancreaticoduodenectomy for periampullary carcinoma. AB - BACKGROUND: Anastomotic leak of the pancreaticojejunostomy is a major cause of morbidity and mortality following pancreaticoduodenectomy. Reports have described a large variety of techniques for performing this anastomosis and managing the pancreatic stump. In an attempt to obviate the pancreaticojejunostomy, we prospectively studied the technique of ligating the pancreatic duct and using external drains to create a temporary controlled pancreaticocutaneous fistula. PATIENTS AND METHODS: Thirty-five consecutive patients who were to undergo pancreaticoduodenectomy for periampullary carcinoma were prospectively randomized to one of two groups: pancreaticojejunostomy (PJ) (n = 18) or controlled pancreaticocutaneous fistula (CPF) (n = 17). The groups were well matched for age, sex, coexisting medical illnesses, type of tumor, and preoperative condition. Except for the management of the pancreatic remnant, all patients in both groups underwent an identical procedure. Major morbidity, length of hospitalization, duration of the controlled pancreatic fistula, and mortality were analyzed over a mean follow-up interval of 26 months (range 5 months to 7.5 years). RESULTS: The CPF group experienced lower overall operative morbidity rates than the PJ group (24% versus 56%, P < 0.01). Two patients (11%) in the PJ group and none in the CPF group died (P = NS). Half the morbidity in the PJ group and both mortalities were related to anastomotic leak. The CPF and PJ groups left the hospital after mean stays of 26.4 and 42.2 days respectively (< 0.01). CONCLUSIONS: Compared to pancreaticojejunal anastomosis, creation of a temporary controlled pancreaticocutaneous fistula in patients who undergo pancreaticoduodenectomy for periampullary malignancy has no appreciable risk. It is associated with reduced morbidity and shorter length of hospitalization. PMID- 7771623 TI - Comparison of serum CA 72-4 and CA 19-9 levels in gastric cancer patients and correlation with recurrence. AB - BACKGROUND: This longitudinal prospective study evaluates the serum levels of the tumor markers CA 72-4 and CA 19-9, alone or in combination, in gastric cancer patients. PATIENTS AND METHODS: Serum tumor markers CA 72-4 and CA 19-9 were measured in 52 patients who had gastric adenocarcinomas and 32 with benign gastric disorders. Serial measurements of these markers were carried out in 30 cancer patients at a median follow-up time of 38 months. RESULTS: CA 72-4 and CA 19-9 had sensitivities of 42% and 46% for the preoperative detection of gastric cancer. Sensitivity for the two combined was 63%. CA 72-4 provided 100% specificity, compared to 72% for CA 19-9. Postoperatively, 17 cancer patients remained disease-free. Sixteen of these maintained normal levels of CA 72-4, and 10 of CA 19-9. Thirteen patients developed recurrent disease. In 9, serum CA 72-4 levels rose from near-normal after surgery and reached diagnostic values approximately 6 months before clinical diagnosis of recurrence. Only 3 patients exhibited such a pattern with CA 19-9. CONCLUSIONS: CA 72-4 is a reliable marker in gastric cancer. Postoperative serial sampling of CA 72-4 may facilitate early identification of recurrences. PMID- 7771624 TI - Atrial myxomas: experiences with 35 patients in Hawaii. AB - BACKGROUND: Thirty-five patients with an intracardiac myxoma underwent excision of the tumor in Hawaii between 1974 and 1993. PATIENTS AND METHODS: There were 28 female and 7 male patients in the group. Their ages ranged from 11 to 79 years (mean 48) with the majority (71%) between 30 and 60 years old. The patients' medical records were reviewed and special attention was paid to clinical presentation, methods of diagnosis, operative findings, and postoperative course. RESULTS: No ethnic predisposition was found. Forty-six percent of the presenting symptoms were cardiac (congestive heart failure 26%, palpitations 14%, and syncope 6%) while arterial embolization accounted for 11%. Diagnosis was made by angiography, echocardiography, or gated cardiac blood pool imaging. All were reliable, but two-dimensional (2-D) echocardiography was used most often, with no false-positive or false-negative results. There were 32 left atrial, 2 right atrial, and 1 biatrial myxomas. Limited septectomy was performed in most cases, but 9 patients (26%) required Dacron patch repair of the atrial septum. There was 1 death from a cerebrovascular accident the day after the removal of a left-sided atrial myxoma. Other patients had few minor postoperative complications. One patient presented with a recurrence 8 years after resection at another institution; no further recurrences were found. CONCLUSIONS: We conclude that due to the non-specific presentation of atrial myxoma, a high index of suspicion is needed. The diagnostic method of choice is 2-D echocardiography. Limited septectomy is a safe procedure, but close follow-up for at least 10 years may be needed to rule out recurrence. PMID- 7771625 TI - Possible role for oxygen free radicals in the regulation of renal nitric oxide synthesis and blood flow. AB - BACKGROUND: This study examines the hypothesis that oxygen radicals down-regulate renal nitric oxide synthesis and contribute to renal vasoconstriction after hemorrhage/reperfusion injury. METHODS: Arterial pressure and renal artery blood flow were measured in anesthetized rats subjected to sham or hemorrhage (30 mm Hg for 30 minutes) followed by blood reperfusion without or with superoxide dismutase, an oxygen radical scavenger. Animals were sequentially injected with 10 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and 200 mg/kg and 400 mg/kg L-arginine, a nitric oxide precursor. RESULTS: The L-NAME treatment increased arterial pressure and decreased renal artery blood flow whereas L-arginine decreased arterial pressure and decreased renal blood flow in the sham animals. Hemorrhage/reperfusion injury attenuated the pressure and renal blood flow changes following L-NAME and L-arginine treatment, which was reversed by superoxide dismutase. CONCLUSIONS: These data suggest that oxygen radicals contribute to the regulation of renal nitric oxide synthesis, contributing to renal artery vasoconstriction following hemorrhage/reperfusion injury. PMID- 7771626 TI - Changes in the surgical management of esophageal cancer from 1970 to 1993. AB - PURPOSE: To evaluate the changes since 1970 in the management and outcome of esophageal resection for cancer. METHODS: The records of all 316 patients who underwent esophageal resection for cancer at University of California Los Angeles Medical Center during the years 1970 to 1993 were reviewed. RESULTS: When records from 1984 to 1993 were compared to those from 1970 to 1983, significant decreases were seen in operative mortality (10% to 3%, P < 0.01), morbidity (72% to 60%, P < 0.05), anastomotic leaks (12% to 5%, P < 0.03), and reoperations (20% to 8%, P < 0.003). Time spent in hospital and in intensive care decreased 40%. These improvements in short-term outcome were most evident in patients with disease in later stages. The 5-year survival rate increased (12% to 21%, P < 0.01). A greater percentage of tumors presented in early stages (21% versus 37%). CONCLUSIONS: Short-term outcome of surgical resection for esophageal carcinoma improved between 1970 and 1993, in part because of changes in perioperative and surgical management. Long-term survival improved, probably due to earlier detection of tumors. PMID- 7771627 TI - Current results of therapy for esophageal perforation. AB - BACKGROUND: Prior reviews of esophageal perforation with delayed recognition have reported mortality rates as high as 66%. We performed a retrospective review of patients with nonmalignant esophageal perforation to assess the outcome of current management techniques. PATIENTS AND METHODS: Charts were reviewed of all patients who were treated for nonmalignant esophageal perforation between 1980 and 1993. They were 23 men and 10 women, mean age 49 +/- 3 years, 19 of whom were diagnosed early (< or = 24 hours) and 14 of whom were diagnosed late (> 24 hours). RESULTS: Perforations were due to instrumentation (16), operative injury (7), spontaneous rupture (4), trauma (4), and other causes (2). Pre-existing esophageal disease was identified in 23 patients (70%), including achalasia (9), stricture (7), varices (5), and other (2). Treatment included closure and fundoplication or muscle wrap (10), closure with or without pleural flap (7), resection only (7), resection and reconstruction (3), drainage only (4), and observation (2). Nonfatal complications included empyema (4), arrhythmia (3), persistent leak following attempted closure (2), and other (5). They occurred in 50% of both the early and late diagnosis groups and were of comparable severity in both. The overall mortality was 9% (3/33). Causes of death were sepsis (1) and multisystem organ failure (2). Mortality was 5% (1/19) in patients diagnosed early and 14% (2/14) of those diagnosed late. CONCLUSIONS: Current mortality rates in nonmalignant esophageal perforation are improved compared to previously published rates of 19% for all patients with the condition, 9% following early and 29% following late diagnosis (47 patients overall). We conclude that, despite a high incidence of associated complications, the survival rate following nonmalignant esophageal perforation is improving and the impact of delayed recognition is decreasing. PMID- 7771628 TI - The effect of Roux-en-Y diversion on gastric and Roux-limb emptying in a rodent model. AB - BACKGROUND: The "Roux stasis syndrome" is characterized by symptoms of upper gut stasis following Roux-en-Y gastrojejunostomy (RG). Whether symptoms result from delayed gastric emptying, altered Roux-limb transit, or both has never been settled, partly because of the difficulty of measuring Roux-limb transit. The aim of this study was to develop a model to simultaneously quantitate Roux-limb transit and gastric emptying. METHODS: Rats underwent vagotomy and antrectomy with RG or Billroth II reconstruction (B-II). Gastrointestinal transit of a solid meal (Technetium-99m sulfur colloid-labelled egg white) was assessed 0.5, 1, and 1.5 hours postprandial (pp). Transit of a liquid marker (Na51-CrO4 injected through an efferent-limb catheter) was measured at 25 minutes pp. RESULTS: Solid gastric emptying was slower in RG than in B-II rats at 60 and 90 minutes pp. More of the solid meal and of the liquid marker was retained in the Roux limb than the efferent limb of the B-II at all time points (P < 0.05). CONCLUSIONS: In a rodent model, Roux-en-Y gastrojejunostomy is associated with delayed gastric emptying and slowed efferent-limb transit of solids and liquids. PMID- 7771629 TI - Conversions and complications of laparoscopic treatment of gastroesophageal reflux disease. Formation for the Development of Laparoscopic Surgery for Gastroesophageal Reflux Disease Group. AB - BACKGROUND: It is now known that laparoscopic surgery is associated with less discomfort and less pain during the patient's postoperative course. Laparoscopic treatment of gastroesophageal reflux disease (GERD) is technically feasible. The advantages of this minimally invasive surgical route seem well adapted to a basically functional surgery. However, it is important to know whether laparoscopic access adds a specific risk to this type of surgery. PATIENTS AND METHODS: A retrospective survey was conducted among members of the Formation for the Development of Laparoscopic Surgery (FDCL) group during 1993. A form was filled in anonymously for each patient who had had either a conversion or a postoperative complication following a laparoscopic procedure for GERD. Items concerned preoperative workup, technical details of surgery, and postoperative course. Another form was used to ascertain how many surgical procedures for GERD had been performed during the same period, either laparoscopically or via an elective laparotomy. Nineteen surgeons from the FDCL group took part in the study. From 1991 to 1993, 758 patients underwent a laparoscopic procedure for GERD, while during the same period 38 patients underwent an elective laparotomy. RESULTS: In the laparoscopic group, there were 294 Nissen, 334 Nissen-Rossetti, and 106 Toupet procedures, and 24 Angelchik prosthesis placements. No deaths occurred. The operation had to be converted to an open procedure in 32 cases (4.2% conversion rate). In 7 cases the conversion was due to an intraoperative complication, whereas in 25 cases the conversion was done because of technical difficulties. In 6 cases an intraoperative complication was treated laparoscopically without conversion. Thirty post-operative complications were recorded (morbidity 4%), leading to a reoperation in 12 cases. Five major complications were observed: 2 esophageal perforations, 2 gastric perforations, and 1 bowel perforation. CONCLUSION: These results compare favorably with those of open surgery and suggest that laparoscopic treatment of GERD is as safe as open surgery when performed by a surgeon experienced in laparoscopy. PMID- 7771630 TI - Endoscopic jejunal access for enteral feeding. AB - Enteral (gut) alimentation appears to offer greater benefit for patients than calories delivered via a parenteral (intravenous) route. Enteral alimentation prevents mucosal atrophy, maintains normal gut flora, decreases bacterial translocation, and enhances enteral immunological competence. Reliable delivery into the jejunum without the placement of an operative feeding tube is difficult, however. We have been interested for some time in endoscopically placing a jejunal tube for enteral nutrition early (within 24 hours) after trauma resuscitation or operation. A simplified technique is described for the endoscopic placement of a jejunal feeding tube, with or without a concomitant percutaneous endoscopic gastrostomy. PMID- 7771631 TI - Laparoscopic continent gastrostomy. AB - Surgical feeding gastrostomy is attended by a significant morbidity and mortality. The percutaneous endoscopic route is regarded as the best method, but it is not feasible in cases with pharyngoesophageal stenosis. We here describe a new method using laparoscopy. The technique is easy to perform. The patient retains continence, with the abdominal wall muscle acting as a sphincteric mechanism around the gastric tube. PMID- 7771632 TI - A technique for the exchange of tunneled polymeric silicone catheters and implantable infusion ports. AB - Tunneled polymeric silicone catheters and implantable infusion ports are used with increasing frequency. Complications may occur with catheter placement or ongoing use. A new technique is described that minimizes the risks associated with catheter reinsertion in patients with tunneled polymeric silicone catheters that are either malfunctioning or mispositioned. This procedure allows for the exchange of these catheters without incurring the risk of a new venipuncture. PMID- 7771633 TI - Esophagogastrostomy anastomotic leaks complicating esophagectomy: a review. AB - PURPOSE: To summarize the most current information about the etiology, pathophysiology, clinical presentation, treatment, and outcome of esophagogastrostomy leaks following esophagectomy. METHOD: The English language literature was searched by manual methods and MEDLINE for original articles reporting results and complications of esophagectomy. RESULTS: Esophagogastrostomy anastomotic leaks cause considerable morbidity and mortality after esophagectomy. Their major etiologic factors are ischemia of the gastric fundus and errors in surgical technique. The clinical presentation of postoperative anastomotic leak ranges from an asymptomatic radiographic finding to a necrotizing thoracic infection. Severity of illness is largely dependent on four factors: gastric viability, the site (thorax or neck) and time of the leak, and its containment by surrounding tissues. Cervical anastomoses have a higher leak rate than thoracic anastomoses, but leaks from thoracic anastomoses are more morbid. CONCLUSION: Leaks from thoracic anastomoses require aggressive surgical treatment. Cervical anastomotic leaks that are truly confined to the neck can usually be managed at the bedside with wound drainage and packing. However, the seriousness of cervical anastomotic leaks should not be underestimated. Some leaks from anastomoses constructed in the neck are, in reality, mediastinal leaks. Selected patients with radiologically detected asymptomatic leaks can be managed conservatively. PMID- 7771634 TI - Carbohydrate-deficient transferrin levels in a female population. AB - Female college students (n = 49) from a small southwestern United States university participated in the 9-month study. Data collected included the assessment of drinking habits and other related substance use habits and serum levels of carbohydrate-deficient transferrin (CDT). Each subject provided an interview and blood sample on three occasions at 90-day intervals. Appended to the interview were a series of questions regarding stage of menstrual cycle and the diagnoses of certain diseases. The CDT values obtained were consistent with those obtained in other studies. Moderate-drinking subjects had significantly higher CDT values than did the abstainers and light drinkers. Females using oral contraceptives had significantly higher CDT values than those who were not taking oral contraceptives. Finally, although CDT values varied over time, they did not appear to vary as a function of menstrual cycle stage. PMID- 7771635 TI - Alcohol and the mystique of flushing. PMID- 7771636 TI - Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics. AB - Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol. PMID- 7771638 TI - Alcohol-related aggression in males and females: effects of blood alcohol concentration, subjective intoxication, personality, and provocation. AB - This study tested the combined predictive ability of blood alcohol concentration (BAC), subjective intoxication, and aggressive personality traits on physical aggression in males and females in High- and Low-provocation conditions. Sixty intoxicated White social drinkers (30 males and 30 females) competed against a fictitious opponent on a modified version of the Taylor aggression paradigm in which subjects both received and delivered electric shocks to their opponents in provoking and nonprovoking conditions. Provocation conditions (High and Low) were defined by the intensity of the shocks the subjects received. Aggression was operationalized as the intensity of the shocks selected by the subjects. Results indicated that, for males in the High-provocation condition, aggressive personality traits, subjective intoxication, and BAC were effective predictors of physical aggression. However, in the Low-provocation condition, only aggressive personality traits and BAC predicted aggression. None of the variables were effective predictors of aggression for intoxicated females. PMID- 7771637 TI - Vasodilatory state of decompensated cirrhosis: relation to hepatic dysfunction, ascites, and vasoactive substances. AB - The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r = -0.64, p = 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r = -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r = -0.53, p = 0.04). Concentrations of S and U digoxin like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771639 TI - Independent associations among maternal alcohol consumption and infant thyroxine levels and pregnancy outcome. AB - Studies with animal models of alcohol-related birth defects (ARBDs) suggest that reductions in circulating thyroid hormones, including thyroxine (T4), may be a persistent postnatal effect of fetal alcohol exposure. The few clinical reports of children with fetal alcohol syndrome (FAS) that address thyroid system function generally reported that FAS children have thyroid hormone levels within normal limits. For the current study, data bases from the Fetal Alcohol Research Center and the Michigan Department of Public Health Newborn Screening Program were assessed to correlate measures of maternal drug use during pregnancy and infant outcome (gestational age at birth, birthweight, "fetal growth"), with infant whole-blood T4 levels. Multiple regression analyses accounted for demographic factors, infant age at testing, and variation in the T4 assay. As expected, alcohol intake and smoking each had a substantial negative impact on birthweight, gestational age at birth, and fetal growth, assessed as birthweight corrected for gestational age. Infant T4 levels were positively related to birthweight and gestational age and were more strongly related to fetal growth. Infant T4 levels were not influenced significantly by either maternal smoking or alcohol consumption. Smoking- and alcohol-related reductions in birthweight, gestational age, or fetal growth were not associated significantly with variations in infant T4. Interesting questions remain regarding species differences and the influences of maternal alcohol consumption on T4 metabolism as a mechanism for ARBDs. However, the current data do not support the hypothesis that maternal alcohol consumption, or smoking, during pregnancy leads to compromised thyroid system function in newborn humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771640 TI - Stress, depression, irrational beliefs, and alcohol use and problems in a college student sample. AB - One-hundred thirty-five alcohol-using college students completed a questionnaire on their levels of alcohol use, moderate-to-severe problems with alcohol use, the Eysenck 1.7 measure of impulsiveness and venturesomeness, the Zung depression scale, the "Hassles and Uplifts" scale of life stresses, and a scale of proneness to irrational beliefs. Impulsivity and venturesomeness were significantly correlated with quantity-frequency of alcohol use, but not with the occurrence of alcohol use problems; whereas depression, stress, and irrational beliefs were significantly correlated with alcohol problems, but not with alcohol use. Multiple regression analyses indicated that the effect of stress on alcohol problems was mediated by depression, whereas the effect of depression, in turn, was mediated by irrational beliefs. PMID- 7771641 TI - Effect of alcohol and electrical stimulation on leakage of creatine kinase from isolated fast and slow muscles of rat. AB - Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber-type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37 degrees C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow-twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol-induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow-twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics. PMID- 7771642 TI - Acute prenatal ethanol exposure and luteinizing hormone-releasing hormone messenger RNA expression in the fetal mouse brain. AB - Ethanol exposure during critical periods of development results in alterations of central nervous system morphology and function. In this study, the effects of acute ethanol exposure on the number of neurons expressing luteinizing hormone releasing hormone (LHRH) messenger RNA (mRNA) has been analyzed. Also, the expression of LHRH mRNA in the diagonal band of Broca/preoptic area (DBB/POA) was determined. Pregnant C57BL/6J mice were intubated with two doses of a 25% solution of ethanol or water (2.9 g/kg body weight) 4 hr apart on gestation day 7 (G7), G10, or G11. Animals were killed on G18, and in situ hybridization was utilized to detect neurons expressing LHRH mRNA. The number of neurons expressing LHRH mRNA was determined along their migration route from the rostrum into the forebrain. Ethanol exposure on G7 did not significantly change the number of neurons expressing LHRH mRNA on G18 compared with that in control animals. However, the number of neurons expressing LHRH mRNA in the nasal septum area in animals exposed to ethanol on G10 or G11 was significantly less than the number in control animals (p < 0.05). Prenatal ethanol exposure on any of the aforementioned treatment days did not alter the expression of LHRH mRNA at the level of the DBB/POA on G18 in ethanol-treated animals compared with control animals. Also, neuron-specific enolase mRNA expression at the level of the DBB/POA was not altered by prenatal ethanol exposure. Therefore, ethanol exposure on the aforementioned treatment days did not differentially affect LHRH mRNA expression compared with neuron-specific enolase mRNA expression at the level of the DBB/POA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771643 TI - Novel synergistic treatment of ethanol withdrawal seizures in rats with dopamine and serotonin agonists. AB - A recent observation in this laboratory of a simultaneous increase in striatal dopamine and a decrease in serotonin in ethanol-dependent rats during ethanol withdrawal prompted studies with combined dopaminergic + serotoninergic agonists to stop withdrawal seizures. Amphetamine (2 mg/kg) + fenfluramine (8 mg/kg) given jointly, but not separately, prevented ethanol withdrawal seizures as effectively as benzodiazepines (chlordiazepoxide), the current drugs of choice. The combination of amphetamine and fenfluramine, unlike chlordiazepoxide, significantly reduced intake of ethanol during and immediately following ethanol withdrawal. PMID- 7771644 TI - Sensitivity of nucleus accumbens neurons in vivo to intoxicating doses of ethanol. AB - The nucleus accumbens septi (NAcc) is considered an important component of the final common pathway involved in the reinforcing properties of ethanol. We studied the effects of intraperitoneal administration of ethanol on spontaneous, glutamate-activated, and fimbria-activated NAcc neurons in acute anesthetized and freely moving unanesthetized rats. Ethanol significantly reduced the firing rate of spontaneous and glutamate-activated NAcc neurons in both electrophysiological preparations. Stimulation of the ipsilateral fimbria evoked single-unit activity in NAcc neurons with two characteristic latencies (early, 7.21 +/- 0.74 msec; late, 18.24 +/- 0.66 msec). Intoxicating doses of ethanol inhibited the recruitment of late, but not of early, fimbria-activated NAcc neurons. These data demonstrate electrophysiological evidence for the existence of neurons in the core region of the NAcc that are sensitive and insensitive to acute systemic ethanol administration. PMID- 7771645 TI - Alcohol, tumor necrosis factor, and tuberculosis. AB - Alcohol exerts potent suppressive effects on the immune system that significantly increase host susceptibility to a variety of infections, particularly pneumonia. Historically, tuberculosis has been strongly associated with alcohol abuse. Although the relationship between alcohol abuse and tuberculosis is widely appreciated, the basic mechanisms by which alcohol immunosuppresses the host remain to be clarified. A major obstacle in furthering our understanding of this association has been the difficulty in distinguishing between the effects of alcohol per se and the other frequent sequelae of alcoholism such as nutritional deficiencies, liver disease, cigarette smoking, hygienic factors, and lifestyle. This article focuses on the role of tumor necrosis factor-alpha (TNF) in host defense and how alcohol modulates the activity of this important cytokine. While TNF's role in mediating the lethal consequences of infection has been the subject of much conjecture, this review focuses on the emerging evidence that TNF is an essential factor in the normal immune response to numerous infections, including tuberculosis. PMID- 7771646 TI - In utero exposure to ethanol affects postnatal development of T- and B lymphocytes, but not natural killer cells. AB - The effect of intrauterine exposure to ethanol on lymphocyte development in the neonatal period was studied in C57BI/6J mice. Mice were bred, and then the female mice were assigned to 1 of 3 diet groups, 25% ethanol-derived calories (EDC), pair-fed control, or ad libitum laboratory chow. At birth, all offspring were cross-fostered to surrogate mothers who had been fed laboratory chow. At weekly intervals, the neonatal mice were weighed, and 4 mice from each group were used to assess the development of splenic lymphocytes. The total number of splenocytes was similar in all three groups at each sampling. The number of T-cells, B-cells, and natural killer (NK) cells was measured by flow cytometry. T-cells and NK cells did not vary significantly among the three diet groups. However, the total number of B-cells was decreased for the first 3 weeks of life in the ethanol exposed animals. The function of the T-cells and B-cells was determined by assessing the response to lipopolysaccharide, pokeweed mitogen, phytohemagglutinin, and concanavalin A. The response to all four mitogens was significantly reduced in the ethanol-exposed animals and did not recover to control levels until 4-5 weeks of life. Ethanol exposure had no significant effect on the kinetics of acquisition of NK lytic function, as assessed by determining the killing of chromium-51 labeled YAC-1 tumor target cells. These data show that prenatal exposure to ethanol causes a transient immunodeficiency in some, but not all compartments of the immune system. PMID- 7771647 TI - Ethanol elevates fetal serum glutamate levels in the rat. AB - Glutamate is an important excitatory neurotransmitter. However, a sustained elevation of glutamate in the extracellular space may be toxic to neurons. Because the blood-brain barrier is incomplete in the developing fetus, an elevation of fetal serum glutamate could expose the immature, growing brain to potentially toxic levels of extracellular glutamate. Chronic ethanol consumption during pregnancy is associated with an increased risk for a complex array of congenital anomalies, including alterations in the CNS, a hallmark of the fetal alcohol syndrome. Some central nervous system changes appear to involve the glutamate receptor, including reduced number and altered function. One mechanism for receptor downregulation may be a sustained elevation in extracellular glutamate. We hypothesize that chronic ethanol exposure during pregnancy leads to an elevation in fetal serum glutamate. When rats were fed ethanol-containing liquid diet throughout pregnancy, growth retardation of fetuses was observed at sacrifice (gestation day 20). Within each group, ethanol-fed, pair-fed, and ad libitum chow-fed, serum glutamate levels were generally higher in the fetus than in the dam. Ethanol treatment had no effect on fetal or maternal serum glutamine, a reciprocal metabolite of glutamate. In contrast, ethanol treatment increased serum glutamate levels in the fetal serum by nearly 50%, compared with either of the control groups. Maternal serum glutamate was not affected. The finding of ethanol-induced elevation of fetal serum glutamate suggests that the developing brain might be concurrently exposed to elevated levels of extracellular glutamate. Chronic exposure to elevated glutamate during critical periods of brain development may contribute to the pathogenesis of the fetal alcohol syndrome. PMID- 7771648 TI - Polymorphism at the P450IIE1 locus is not associated with alcoholic liver disease in Caucasian men. AB - Because alcoholic hepatitis and cirrhosis, well-known complications of alcohol abuse, do not occur in all alcoholics, genetic factors such as differences in alcohol-metabolizing enzymes may play a role in the development of alcoholic liver disease. Cytochrome P450IIE1 catalyzes the oxidation of ethanol, producing acetaldehyde and free radicals capable of reacting with and peroxidizing cell membranes. Polymorphisms have been identified in the 5'-flanking region of the P450IIE1 gene that may alter the transcriptional activity of the gene. In this study, we analyzed the P450IIE1 genotypes at the polymorphic PstI and RsaI restriction enzyme sites in 53 Caucasians with severe alcoholic liver disease to determine if there is an association between these polymorphisms and alcoholic liver disease. Subjects that tested positive for the hepatitis C virus were eliminated from the study. To identify the type A (homozygous for the c1 gene), type B (heterozygous for the c1 and c2 genes), and type C (homozygous for the c2 gene) genotypes at the P450IIE1 locus, DNA encompassing the polymorphisms was amplified by polymerase chain reaction, slot-blotted, and probed with allele specific oligonucleotides. Allele frequencies for the c1 allele were 0.95 for alcoholics with severe liver disease, 0.95 for alcoholics without liver disease, and 0.98 for the general population. No differences in allele frequencies between alcoholic patients with severe liver disease and alcoholics without liver disease were observed. PMID- 7771649 TI - Human stomach class IV alcohol dehydrogenase: molecular genetic analysis. AB - A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high Km values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the coenzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH. PMID- 7771650 TI - Quantitative changes in G proteins do not mediate ethanol-induced downregulation of adenylyl cyclase in mouse cerebral cortex. AB - Our prior work, and the work of others, demonstrated that chronic administration of ethanol to cells in culture or to mice resulted in decreased responsiveness of adenylyl cyclase (EC4.6.1.1) to a number of stimulatory agents. In this study, we substantiated the ethanol-induced changes in cerebral cortical adenylyl cyclase activity in alcohol-tolerant and alcohol-dependent mice, and we examined whether chronic ethanol treatment of mice altered the quantity of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) in cerebral cortex and other mouse brain areas. Amounts of various G protein subunits--including the alpha subunits of GS (GS alpha), Gi alpha 1-3, G(o) alpha, and beta subunits--were examined by Western blot analysis. There was no change in quantity of these G protein subunits in cerebral cortex, hippocampus, or cerebellum of ethanol-fed mice, compared with controls. In striatum of ethanol-fed mice, small increases in Gi alpha 1 and G(o) alpha were observed, but these changes could not explain the ethanol-induced desensitization of adenylyl cyclase in brain areas such as the cerebral cortex. Forskolin activation of cerebral cortical adenylyl cyclase activity showed two components of activation, with high and low "affinity" for forskolin. Ethanol treatment caused a decrease in the efficacy of forskolin for both components, whereas the EC50 of forskolin for each component did not change. Adenylyl cyclase activity measured in the presence of manganese was also diminished in cortical membranes of ethanol-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771651 TI - Altered ACTH and corticosterone responses to interleukin-1 beta in male rats exposed to an alcohol diet: possible role of vasopressin and testosterone. AB - We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL 1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771652 TI - Ethanol's effect on tissue polyamines and ornithine decarboxylase activity: a concise review. AB - An extraordinarily diverse literature describes the cellular/tissue systems in which the molecular effects of both acute and chronic alcohol exposure seem to be mediated by changes in polyamine levels and/or ornithine decarboxylase (ODC) activity. The single unifying factor that links most of these studies is that they all, in some way, involve tissues that are undergoing relatively rapid cell division. Non-dividing cells expressing the NMDA receptor are a notable exception in that ethanol and the polyamines seem to act via discrete regions of that receptor. Under most cellular conditions, ODC activity is a reflection of the relative tissue polyamine content, and an increase in ODC activity and polyamine content seems to be one of the early events in the progression of quiescent cells toward cell division. Thus, it is not surprising that ethanol, which has been widely reported to delay cell division, should be found to interact with the ODC/polyamine pathway. Perhaps the most unique aspect of these studies is the fact that, with rare exception, both acute and chronic ethanol exposure have been found to slow growth and to lower tissue polyamine (putrescine) content. Furthermore, in most studies, the ethanol-induced suppression of cell division could be overcome by the administration of exogenous putrescine. These data suggest that the ethanol-induced suppression of cell division resulted from the loss of putrescine. In addition, because the cells were able to respond to the exogenous putrescine, the studies suggest that the signaling pathway remained intact beyond the polyamine synthesis step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771653 TI - Ethanol increases GABAA responses in cells stably transfected with receptor subunits. AB - Ethanol enhancement of GABAA receptor function has been found in some, but not all, studies. These results suggest the existence of ethanol-sensitive and resistant receptors that may differ in subunit composition, although methodological differences (e.g., 36Cl- flux versus membrane currents) could also contribute to the different results. To examine these possibilities, we used mouse L(tk-) cells stably transfected with alpha 1 + beta 1 or alpha 1 + beta 1 + gamma 2L GABAA receptor subunit DNAs and compared 36Cl- flux with whole-cell, patch-clamp measurements of GABAA receptor function. Both techniques detected a similar modulation of the GABA receptor by ethanol, flunitrazepam, and pentobarbital. The potentiating action of ethanol required the gamma-subunit and was maximal at a concentration of 10 mM. Similar ethanol potentiation was obtained with brief (20 msec) or long (2 sec) applications of GABA. Analysis of data obtained from individual cells expressing alpha 1 beta 1-gamma 2L subunits showed considerable variability in sensitivity to ethanol, particularly with concentrations of 30 and 100 mM. Ethanol potentiated GABA action if the cells were grown on coverslips coated with polylysine, but had no effect on GABAA receptors of cells grown on uncoated coverslips. Thus, ethanol action was influenced by the growth matrix. Taken together, these data indicate that a gamma subunit is necessary, but not sufficient, for ethanol sensitivity in this cell system. We suggest that posttranslational processing, particularly receptor phosphorylation, may also be important and that stably transfected cells will be useful in elucidating these events. PMID- 7771654 TI - Cell cycle kinetics in fetal rat cerebral cortex: effects of prenatal treatment with ethanol assessed by a cumulative labeling technique with flow cytometry. AB - The effects of ethanol on the cell cycle kinetics of cortical precursor cells during the period of cortical neuronogenesis [between gestational day (G) 12 and G21] was systematically examined. Samples of dissociated cortical cells were harvested from the cerebral cortices of 13-, 15-, 17-, 19-, and 21-day-old fetuses. The fetuses were obtained from pregnant rats: (a) fed a liquid diet containing 6.7% (v/v) ethanol (Et) ad libitum, (b) pair-fed an isocaloric liquid control diet (Ct), or (c) fed chow and water (Ch) ad libitum. Before harvesting the cells, the fetuses were administered a series of 1-5 injections of bromodeoxyuridine (BrdU). The proportion of cells that incorporated the BrdU was assessed. Using these raw data, the S-phase length (Ts), total cell cycle length (Tc), and the growth fraction (GF; the fraction of the total population that was actively cycling) were determined with a cumulative labeling procedure. The Ts was approximately 8-9 hr, regardless of either the date of the injection or the dietary treatment of the dam. On the other hand, the Tc for the Ct- and Ch treated rats increased over the gestational period. That is, the Tc was shortest on G13 and longest on G21. The Tc for Et-treated rats, however, did not change between G13 and G21. For the Ch- and Ct-treated groups, the GF decreased > 15 fold between G13 and G21. The decline (5-fold) for the Et-treated group over the same period, however, was not as great as it was for the Ct-treated fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771655 TI - Effects of prenatal exposure to alcohol plus caffeine in rats: pregnancy outcome and early offspring development. AB - The factors determining susceptibility to fetal alcohol syndrome (FAS) are not fully understood. We used an animal model of alcohol-related birth defects to assess the coteratogenic potential of caffeine as a risk factor in FAS. Rats were exposed prenatally to alcohol (approximately 15 g/kg/day) with or without caffeine (approximately 84 mg/kg/day) from gestation days 6 through 20 via liquid diet. All control groups were pair-fed to the alcohol-exposed groups. In addition, some controls had free access to lab chow and water. Prenatal exposure to alcohol or caffeine reduced both maternal weight gain during pregnancy and birth-weight of offspring. The combination of alcohol plus caffeine produced an additive effect in reducing birthweight and synergistic effects in increasing postnatal offspring mortality. Prenatal alcohol exposure had a significant negative impact on several developmental indices, including grip strength and negative geotaxis. Prenatal caffeine exposure did not affect maturational measures and did reduce offspring serum levels of the zinc-dependent enzyme alkaline phosphatase. This study in rats demonstrated that caffeine can exacerbate some of the effects of alcohol on prenatal development, specifically reduced birthweight, litter size, and postnatal survival, but that caffeine does not appear to alter prenatal alcohol-induced delays in early postnatal maturation of survivors. The relative impact of intralitter birthweight rank on developmental outcome was also assessed. PMID- 7771656 TI - Molecular biological aspects of alcohol-induced liver disease. AB - Molecular biological investigations have become a predominant methodology applied to the study of alcohol-induced liver disease. The enzymatic pathways responsible for ethanol metabolism, and their genetic as well as environmental control, have become the focus of detailed investigation. More recently, the significance of cytokines in the pathogenesis of alcohol-induced liver disease has also become a major area of speculation. This review focuses on the advances made in studies of two important enzymes responsible for alcohol metabolism, alcohol dehydrogenase and aldehyde dehydrogenase, as well as the investigation of the proinflammatory and profibrogenic cytokines involved in the process of hepatic fibrogenesis. The quality and quantity of new discoveries made in the field of alcohol-induced liver disease is impressive, especially when one realizes that molecular biological approaches have been employed in this area for only 15 years. However, in most cases the studies have been predominantly descriptive, with little direct relevance to the therapeutics of alcoholism and alcohol-induced organ injury. Because the groundwork has been laid, one hopes that the next 15 years will rectify this failure. PMID- 7771657 TI - Correlates of alcohol-related problems in African-American and white gynecologic patients. AB - The purpose of this study was to assess racial differences in the risk of alcohol related problems associated with alcohol consumption, regular psychoactive drug use, a family history of alcohol-related problems, sociodemographic factors (age and education), and social roles (work, marital, and parental) among nonabstaining African-American and White gynecologic outpatients. In addition, work, marital, and parental roles were investigated to determine whether they mediated or explained racial differences observed in relationships between these factors and alcohol-related problems. Respondents were 630 African-American women and 769 White women aged 13-77 who were systematically sampled from three obstetric/gynecologic clinics and two private practices in Erie County, New York. Hierarchical multiple regression analysis was used to test the significance of main effects of these factors on alcohol-related problems, to test the interactive effects of race with each factor, and to test the interactive effects of social roles with alcohol consumption, the only factor for which a racial difference was observed in its relationship with alcohol-related problems. Overall, results indicated that correlates of alcohol-related problems were similar for African-American and White women. Higher risk of alcohol-related problems was associated with lower levels of education and lack of work and parental roles. In addition, married women who drank heavily were at higher risk of alcohol-related women who drank heavily were at higher risk of alcohol-related problems than unmarried women who drank heavily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771658 TI - Effects of neonatal ethanol exposure on saccharin consumption. AB - Prenatal ethanol exposure has been associated with alterations in a variety of sexually dimorphic behaviors in rats. This study examined the effects of neonatal ethanol exposure on saccharin consumption, a sexually dimorphic behavior in rats. Subjects were Sprague-Dawley rats that were artificially reared (AR) from postnatal day (PN) 4-PN12 through gastrostomy tubes with ethanol exposure limited to PN4-PN10. The AR groups included two ethanol doses (6 g/kg/day and 4 g/kg/day) and an isocaloric maltose-dextrin control. A sham surgery control group was also included. The AR subjects were returned to their dams on PN13. At 21 days of age, subjects were housed with one same-sex sibling and free access to rat chow and water until testing. Subjects were tested for saccharin preference and consumption at 110 days of age. Typically, male rats consume less saccharin than females, and this was evident in the 4 g/kg ethanol group and both control groups. However, this was not apparent among the 6 g/kg ethanol-exposed males. Furthermore, saccharin preference seemed to be reduced in the females exposed to 6 g/kg ethanol. These data suggest that the "sensitive period" for ethanol's effects on sex differences in saccharin consumption extends into postnatal life. PMID- 7771659 TI - Tuberculosis in the 1990s. AB - The steady decline in tuberculosis case rate reversed in the mid-1980s, and tuberculosis cases have increased dramatically since that time. Important factors contributing to this increase are the human immunodeficiency virus (HIV) epidemic and tuberculosis occurring in foreign-born persons. Tuberculosis outbreaks have occurred in HIV clinics and wards, prisons, homeless shelters, nursing homes, and health care facilities. Some of the outbreaks have involved strains of tuberculosis resistant to multiple antituberculosis drugs. Recent recommendations for initial therapy of tuberculosis include the use of four drugs and directly observed therapy in an effort to prevent the emergence of further drug resistance. PMID- 7771660 TI - Antisocial tendencies and cortical sensory-evoked responses in alcoholism. AB - Alcohol-dependent patients with antisocial, aggressive, and impulsive behaviors form a subgroup, in which a dysfunction of the brain serotonin system is discussed as a pathogenetic factor. Early onset and a transmission from fathers to sons (type II alcoholism; Cloninger, 1987) are supposedly further characteristics of this subgroup. The response pattern of primary auditory cortices to auditory stimuli with different intensities is discussed as a noninvasive indicator of the level of central serotonergic neurotransmission. A strong intensity dependence of these responses is supposed to indicate low serotonergic neurotransmission and vice versa. A strong intensity dependence is therefore expected to characterize patients with antisocial tendencies. Auditory evoked potentials (N1/P2 component) to stimuli in five different intensities were recorded in 53 hospitalized patients after 1 week of withdrawal. Dipole source analysis was performed to separate responses of primary and secondary auditory cortices. Patients with antisocial tendencies showed a significantly stronger intensity dependence of their evoked responses of primary auditory cortices (tangential dipoles). Age at onset and family history were not related to the intensity dependence of the evoked responses. The results support the notion that alcohol-dependent patients with strong intensity dependence and antisocial tendencies form a subgroup with a serotonergic hypofunction. These patients may respond favorably to a relapse prevention with serotonergic drugs. PMID- 7771661 TI - Personality and EEG beta in older adults with alcoholic relatives. AB - Research indicates that biological relatives of alcoholics are more likely to develop alcoholism than individuals without alcoholic relatives. Most research on these groups had focused on individuals who were relatively young (i.e., under 30 years old). In the present study, we evaluated middle-aged and elderly nonalcoholic men and women who did and did not have alcoholic biological relatives to assess factors that might be involved in a later, rather than an earlier, onset of alcoholism. Psychological characteristics were assessed using the Tridimensional Personality Questionnaire. Biological characteristics were assessed using quantitative measures of the spontaneous electroencephalogram. The psychological measures did not distinguish the groups, but biological measures did. The results indicated that nonalcoholic individuals with alcoholic relatives showed elevated beta as compared with sex- and age-matched control subjects. Factors that might have mediated these findings are discussed, as are the implications of these outcomes. PMID- 7771662 TI - Routine activities and alcohol use: constraints on outlet utilization. AB - Studies of consumers' use of alcohol beverage outlets have provided a basis for understanding drinking behaviors in different drinking environments. These studies have shown that drinking environments are related to both demographic and drinking pattern measures. Absent from these studies has been a theoretical basis on which to make predictions regarding drinking patterns and choices of drinking environments under the various social, economic, and environmental constraints typically confronting alcohol consumers. This study presents one such theoretical approach. The approach assumes that, in the context of individual preferences for alcohol, drinking choices are constrained by consumers' economic and time-energy budgets for consumption. All other things being equal, it is suggested that greater budgets for consumption will be related to greater alcohol use, quality of beverages purchased, amenity values of purchase locations, or all three. Because on-premise drinking entails greater economic costs, greater drinking levels will be related to lower utilization of on-premise establishments. The predictions of this approach were tested using data obtained from telephone surveys of consumers conducted in 1990 and 1991. The results showed that controlling for income, variables related to greater time-energy budgets for consumption (i.e., marital status and household composition) were related to greater consumption levels and greater utilization of on-premise establishments. Controlling for demographic measures, greater income was related to greater utilization of restaurants and increased beverage quality. Controlling for all other measures, frequencies of consumption were inversely related to consumption at on-premise establishments, reflecting the expected moderation in costs for heavier consumers on a limited alcohol budget. PMID- 7771663 TI - High-risk drinking across the transition from high school to college. AB - Alcohol use and related problems were studied from the senior year in high school to the first autumn in college for 366 heavy drinking students. Four risk factors subject sex, family history of drinking problems, prior conduct problems, and type of college residence-were evaluated as predictors of: (1) differential changes in drinking rates, (2) differential changes in alcohol-related problems, and (3) alcohol dependence symptoms during the first college term. Results suggest that both dispositional and environmental factors are associated with changes in drinking rates and the existence of dependence symptoms. Increases in the frequency of drinking were specifically and strongly associated with residence in a fraternity (men) or sorority (women). Three risk factors were associated with increased quantity of drinking: male gender, residence in a fraternity or sorority, and a history of conduct problems. Prior conduct problems were also consistently associated with dependence symptoms during the first term in college. A family history of alcohol problems was not consistently related to changes in use rates or problems, although some analyses suggest interactive effects. Early interventions on college campuses should target individuals using additive risk profiles. PMID- 7771664 TI - Pulmonary host defenses. AB - Well functioning host defenses in the respiratory tract effectively remove microbes and other debris that reach the conducting airways and alveoli, and this usually prevents infections. People with acute and chronic illnesses can experience failure of any number of these defense mechanisms that allow pneumonia (and bacteremia) to occur, often with considerable morbidity and mortality. People with alcohol-related illnesses are a susceptible group for infections, and many strategies are needed to help them such as moderating alcohol abuse and dependence, providing timely immunizations to create antibody against encapsulated bacteria, anticipating microbial colonization of mucosal areas that can promote infection, giving excellent supporting medical care in crisis situations, and prescribing appropriate antibiotics. New approaches to boosting inflammatory reactions to control lung infections better with cytokines and new immunomodulator therapies must be investigated now. PMID- 7771666 TI - Variation in the association of alcohol consumption with five DSM-IV alcohol problem domains. AB - Data from a nationally representative sample of the U.S. adult population were used to investigate the association between alcohol consumption and five discrete problem domains included in the DSM-IV formulations for alcohol abuse and dependence. Two dimensions of consumption were considered in the analysis: average daily ethanol intake and the relative frequency of drinking five or more drinks. The sample consisted of 22,102 adults defined as current drinkers. After controlling for various sociodemographic characteristics, family history of alcoholism, and age at onset of drinking, both consumption measures retained significant levels of association within all five problem domains. The magnitudes of the odds ratios at selected levels of consumption were approximately 50% greater for the domains of impaired control, continued drinking despite problems and hazardous drinking than for the domains of tolerance and withdrawal. Moreover, the factors that modified the effect of the consumption measures varied markedly across domains, with age, college education, and race the most consistent modifiers of the effect of alcohol consumption. PMID- 7771665 TI - Blunted growth hormone response is associated with early relapse in alcohol dependent patients. AB - Growth hormone (GH) secretion, stimulated by the dopamine D1 and D2 receptor agonist apomorphine, was assessed in 55 alcohol-dependent patients before detoxification (on the day of admittance to hospital) and after 7 days of treatment on the ward (day 8). Patients who relapsed early (i.e., within 3 months after detoxification) showed significantly blunted GH secretion before detoxification, compared with both healthy controls and patients who abstained for 6 months. Among early relapsing patients, GH secretion was blunted whether or not patients were acutely intoxicated on the day of admittance to hospital. However, for patients who abstained during observation, a blunting effect of acute ethanol consumption on GH secretion was demonstrated. On day 8, a trend toward blunted GH secretion was found in early relapsing patients only when GH response over infusion time was assessed. Therefore, GH blunting, and no other variable indicating the clinical course of the disease, was associated with early relapse in alcohol-dependent patients. These findings are evidence of reduced dopamine receptor function in a subgroup of early relapsing alcohol-dependent patients during chronic intoxication. PMID- 7771667 TI - Prevalence of cholelithiasis according to alcoholic liver disease: a possible role of apolipoproteins AI and AII. AB - Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholelithiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein AII as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0.0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy-proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13). Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 +/- 9 years, mean +/- SD vs. 45 +/- 11, p = 0.003) with lower apolipoprotein AI (118 +/ 37 vs. 163 +/- 45 mg/dl; p = 0.002) and apolipoprotein AII (30 +/- 12 vs. 53 +/- 20 mg/dl; p = 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771669 TI - The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. AB - It has been suggested that a crucial dimension of alcohol "craving" includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. An interview-based rating scale, the Yale-Brown Obsessive Compulsive Scale-heavy drinkers (YBOCS-hd), has been found useful in quantifying this concept in alcohol-dependent individuals. A self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) has been developed by us as a modification of the YBOCS-hd. The YBOCS-hd showed excellent interrater reliability in our hands. The correlation between the YBOCS-hd and the OCDS total scores obtained on 60 alcohol-dependent individuals was 0.83. The test-retest correlation for the OCDS total score was 0.96, and the obsessive and compulsive subscales test-retest correlations were 0.94 and 0.86, respectively. The internal consistency of the items in the OCDS was high (0.86) and did not improve significantly with removal of individual items. The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only approximately 20%, indicating that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent individuals. When used during a prospective 12 week treatment research study, initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence, because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771668 TI - Alcoholism among four aboriginal groups in Taiwan: high prevalences and their implications. AB - An epidemiological study of alcohol use disorders was conducted on population samples from four aboriginal groups in Taiwan (a total of 993 subjects). The survey involved ethnographic observation and a semistructured psychiatric interview. The interview covered a detailed symptom profile that allowed diagnoses to be made according to different diagnostic criteria. The lifetime prevalences of alcoholism according to the ICD-10 (research criteria) and the DSM III-R criteria were found to be 42.2-54.7% and 44.2-55.5%, respectively, much higher than the rates found in an earlier study (0.11-0.16%) conducted 40 years ago. Men in all groups were found to have higher prevalences, a lower mean age at onset, and a longer mean duration (except in one group) of alcoholism than women. Differences in the distribution of sociodemographic correlates (age, sex, marital status, education, and ethnicity) of ICD-10 harmful use of alcohol and alcohol dependence were examined by case-control analysis with logistic regression. The lifetime prevalences of alcohol use disorders were higher than in recent epidemiological surveys conducted elsewhere. Possible biological and sociocultural explanations for the high prevalence of alcoholism among the study populations are discussed. PMID- 7771670 TI - 1995 Research Society on Alcoholism Meeting. Steamboat Springs, Colorado, June 17 22, 1995. Abstracts. PMID- 7771671 TI - Sensing with chemically and biologically modified carbon electrodes. A review. PMID- 7771672 TI - Development of a novel luminol-related compound, 3-propyl-7,8-dihydropyridazino [4,5-g]quinoxaline-2,6,9(1H)- trione, and its application to hydrogen peroxide and serum glucose assays. AB - Manual and flow injection methods with chemiluminescence detection were developed for the determination of hydrogen peroxide (H2O2) using a novel luminol-related compound, 3-propyl-7,8-dihydropyridazino[4,5-g]quinoxaline-2,6,9(1H)-trione (PDIQ), having a higher efficiency than luminol. The methods are based on the chemiluminescence produced by the reaction of H2O2 with PDIQ in the presence of microperoxidase in alkaline media. Detection limits for manual and flow injection methods are 13 pmol per 100 microliter of test solution and 1.3 pmol per 100 microliter injection volume, respectively, at a ratio of chemiluminescence intensities (or peak heights) of test to blank of 2. The manual method was applied to the determination of glucose in human serum. The method correlated well with the conventional spectrophotometric method (4 = 0.998). PMID- 7771673 TI - Involvement of sulfhydryl groups in the stable fluorescent derivatization of proteins by o-phthalaldehyde. AB - Treatment of human alpha-1-proteinase inhibitor (alpha-1-PI) with o phthalaldehyde (OPA) at pH 8.0 and 25 degrees C, in the absence of added thiol resulted in the formation of a mixed population of fluorescent and non fluorescent isoindoles. The stoichiometry of isoindole formation was tentatively calculated to be 6:1 for unreduced alpha-1-PI and 10:1 for inhibitor treated with dithioerythritol, implicating not only cysteine but also non-sulfur nucleophilic centres as reaction partners. Despite the apparent involvement of the single cysteine residue in alpha-1-PI in the over-all derivatization process, the extent of fluorescent derivatization was independent of the redox state of the inhibitor. Hence the fluorescing moiety was not a 1-alkylthio-2-alkyl-substituted isoindole, as generally observed. The finding that isoindole formation in proteins is not limited by sulfhydryl content and that fluorescent products may originate from amino acid(s) other than cysteine cautions against interpreting fluorescent derivatization by OPA as evidence for cross-linking of lysine to cysteine residues. PMID- 7771674 TI - Determination of substrates using poly(ethylene glycol)-stabilized dehydrogenase enzymes by microlitre per minute flow injection. AB - Flow injection (FI), at a flow rate of microliter min-1, is an effective method for enzymic substrate determination using low concentrations of poly(ethylene glycol) (PEG)-stabilized soluble enzymes. PEG stabilizes dehydrogenase enzymes for at least several days by promoting sub-unit association. Band broadening of knitted open tubular reactors is reduced as flow rate decreases below 300 microliter min-1 and a small tubing diameter is important for a faster rate of absorbance signal increase with residence time. Small (0.5 microliter) sample injections also ensure narrow FI peaks. The determination of several substrates such as pyruvate, lactate, and cortisone using appropriate PEG-stabilized enzymes is demonstrated with this FI instrument at 25 or 50 microliters min-1 with sample throughputs of the order of 2-3 min per sample. The determination of lactate in serum samples is also possible. The advantage of this method, sample throughput, is not sacrificed but enzyme consumption is considerably less, compared to standard ml min-1 FI. PMID- 7771675 TI - Orthogonal array design as a chemometric method for the optimization of analytical procedures. Part 5. Three-level design and its application in microwave dissolution of biological samples. AB - The theory and methodology of a three-level orthogonal array design as a chemometric method for the optimization of analytical procedures were developed. In the theoretical section, firstly, the matrix of a three-level orthogonal array design is described and orthogonality is proved by a quadratic regression model. Next, the assignment of experiments in a three-level orthogonal array design and the use of the triangular table associated with the corresponding orthogonal array matrix are illustrated, followed by the data analysis strategy, in which significance of the different factor effects is quantitatively evaluated by the analysis of variance (ANOVA) technique and the percentage contribution method. Then, a quadratic regression equation representing the response surface is established to estimate each factor that has a significant influence. Finally, on the basis of the quadratic regression equation established, the derivative algorithm is used to find the optimum value for each variable considered. In the application section, microwave dissolution for the determination of selenium in biological samples by hydride generation atomic absorption spectrometry is employed, as a practical example, to demonstrate the application of the proposed three-level orthogonal array design in analytical chemistry. PMID- 7771677 TI - Determination of lasalocid in eggs using liquid chromatography-electrospray mass spectrometry. AB - A method is presented for the determination of the polyether ionophore, lasalocid, in eggs. Samples are extracted under acidic conditions using acetonitrile and the extracts are cleaned up using a simple liquid-liquid extraction step. Lasalocid is detected and quantified using liquid chromatography electrospray mass spectrometry on a quadrupole bench-top instrument. The technique is highly sensitive, with a detection limit of about 0.5 ng g-1 of lasalocid in homogenized egg samples. PMID- 7771676 TI - Naphthalene contamination of sterilized milk drinks contained in low-density polyethylene bottles. Part 2. Effect of naphthalene vapour in air. AB - A survey on naphthalene vapour in air was conducted, revealing that the ambient atmosphere contained concentrations of naphthalene in the range of 0.005-0.100 mg m-3. The level of naphthalene vapour in air increased to 0.35 and 4.00 mg m-3 in places exposed to lacquer paint and naphthalene-based moth-repellent, respectively. The effect of naphthalene vapour in air on milk drinks contained in low-density polyethylene (LDPE) bottles was assessed. A mathematical model was suggested to describe the migration of naphthalene from the atmosphere into milk. The model was proved to be valid for milk drinks exposed to naphthalene-based moth-repellent during storage. Moreover, the extent of migration was found to increase with the fat content of foods, which might be ascribed to an increase in diffusion, in addition to the kinetic factor, that affects naphthalene migration. PMID- 7771678 TI - Determination of free hydroxyproline and proline in human serum by high performance liquid chromatography using 4-(5,6-dimethoxy-2 phthalimidinyl)phenylsulfonyl chloride as a pre-column fluorescent labelling reagent. AB - A fluorescent labelling reagent, 4-(5,6-dimethoxy-2-phthalimidinyl)phenylsulfonyl chloride, was designed for the determination of amines by precolumn HPLC and was applied to the simultaneous determination of hydroxyproline and proline in serum. The reagent reacted with hydroxyproline and proline at 30 degrees C for 10 min to produce the fluorescent derivatives, which were separated on a reversed-phase column by gradient elution with phosphate buffer (1 mmol l-1, pH 7) and acetonitrile and detected by fluorescence measurement at 315 nm (excitation) and 385 nm (emission). The detection limits (signal-to-noise ratio = 3) for both hydroxyproline and proline were 10 fmol per injection. The within-day (n = 10) and day-to-day (n = 5) relative standard deviations using human sera were less than 2.16% and 2.75%, respectively, for hydroxyproline and less than 2.30% and 3.25%, respectively, for proline. The concentrations of free hydroxyproline and proline in normal human sera (n = 13) were 5.6-18.0 and 137.6-252.6 mumol l-1, respectively. The proposed method was also applied to the determination of hydroxyproline and proline in sera from patients with chronic renal failure. The mean concentrations of hydroxyproline and proline in chronic renal failure were about 2.6 and 1.6 times higher, respectively, than those in normal human sera. PMID- 7771679 TI - Fractionation of an antiserum to progesterone by affinity chromatography: effect of pH, solvents and biospecific adsorbents. AB - Several progesterone-AH Sepharose 4B matrices were prepared as biospecific adsorbents suitable for affinity chromatography to fractionate antibodies of different affinity and specificity from a polyclonal antiserum to progesterone-11 alpha-hemisuccinate-BSA. From an affinity column of progesterone-11 alpha hemisuccinate-AH Sepharose 4B no antibodies can be eluted, even with glycine buffer (pH 2.6) and 30% of 2-methoxyethanol. The use of biospecific adsorbents, prepared by coupling with AH Sepharose 4B progesterone derivatives [5-pregnene 3,20-dione di(ethyleneacetal)-11 alpha-ol-11 alpha-hemisuccinate; 4-pregnene 11,20 beta-diol-3-one-11 alpha-hemisuccinate 20 beta-benzoate; progesterone-3 carboxymethyloxime] having a low cross-reactivity with the antiserum, makes the elution of various antibody fractions of variable affinity and specificity possible. 2-Methoxyethanol or N,N-dimethylformamide gradients, in acetate or TRIS buffer, were equally efficient for fractionating the antiprogesterone serum, while a decreasing pH gradient was less effective and eluted antibody fractions that were further separated into various binding components by a solvent gradient. Antibodies eluted from the affinity columns by an eluent containing a high solvent concentration have affinities higher than antibodies eluted at lower solvent concentration. PMID- 7771680 TI - Determination of manganese in Chinese tea leaves by a catalytic kinetic spectrophotometric method. AB - The catalytic effect of manganese(II) on the oxidation of Rhodamine B with potassium periodate in the presence of 1,10-phenanthroline in acetic acid-sodium acetate was studied. A catalytic kinetic spectrophotometric method for determination of manganese(II) was developed. Manganese in the range 0.1-5.0 ng ml-1 can be determined, and the detection limit is 0.02 ng ml-1. Manganese in Chinese tea leaves was successfully determined. PMID- 7771681 TI - Automated determination of inorganic mercury in blood after sulfuric acid treatment using cold vapour atomic absorption spectrometry and an inductively heated gold trap. AB - Inorganic mercury (InoHg) in whole blood and erythrocytes was determined by cold vapour atomic absorption spectrometry (CVAAS) after overnight treatment with sulfuric acid at 45 degrees C and reduction with SnII in the acidic mixture. Total mercury (TotHg) was determined after digestion with a mixture of nitric and perchloric acids. Mercury vapour was preconcentrated on an amalgamation trap made of gold wire. The mercury was rapidly released by inductive heating of the trap. InoHg could be determined specifically in the presence of methylmercury (MeHg). The concentration of MeHg could be calculated by subtracting the concentration of InoHg from that of TotHg. Calculated concentrations of MeHg in erythrocytes showed a strong correlation with the results of a gas chromatographic method, though a discrepancy in calibration was indicated. The detection limits (3 s) in blood (0.5 g) were 0.06 ng g-1 for TotHg and 0.04 ng g-1 for InoHg and S(r) for a 5 ng g-1 whole blood sample was 2% (n = 10) for both TotHg and InoHg. PMID- 7771682 TI - Three-dimensional observation with a confocal scanning laser microscope of fibronectin immunolabeling during cardiac looping in the chick embryo. AB - From the beginning of cardiac myofibrillogenesis in the chick embryo, developing myofibrils at the bottom of the inner myocardial cell layer facing the cardiac jelly are already aligned circumferentially in the direction of the heart tube. To elucidate the mechanism of this alignment, we investigated the temporal and spatial expression of fibronectin and its relationship to actin filaments before and during looping (4- to 13-somite stages) by using a confocal scanning laser microscope. Serial optical tomograms were obtained from whole-mounted heart tubes stained with fluorescein-conjugated antibody against cellular fibronectin and rhodamine-conjugated phalloidin. Before looping (4- to 7-somite stages), particulate and speckled fibronectin formed loose networks. At the onset of looping (8- to 9-somite stages), fine fibrils of fibronectin appeared. They became dense and were arranged circumferentially in the direction of the heart tube. They were aligned parallel with the thick actin bundles that appeared as an initial stage of developing myofibrils. During looping, (10- to 13-somite stages), fibronectin fibrils were fragmented and showed a speckled pattern, while the number of circumferentially aligned mature striated myofibrils increased. These observations suggest that the temporal arrangement of fibronectin fibrils at the beginning of looping plays a role in the circumferential alignment of developing myofibrils. PMID- 7771683 TI - Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI-tracing. AB - Results from functional studies point to the importance of chemoreceptive endings in the duodenum innervated by vagal afferents in the regulation of gastrointestinal functions such as gastric emptying and acid secretion, as well as in the process of satiation. In order to visualize the vagal sensory innervation of this gut segment, vagal afferents were selectively labeled in vivo by injecting the lipophilic carbocyanine dye DiI into either the left or the right nodose ganglion of young adult rats. Thick cryostat sections or whole mounted peels of muscularis externa or submucosa of formalin-fixed tissue were analyzed with conventional and/or confocal microscopy. In the mucosa, many DiI labeled vagal afferent fibers were found with terminal arborizations mainly between the crypts and the villous lamina propria. In both areas, vagal terminal branches came in close contact with the basal lamina, but did not appear to penetrate it so as to make direct contact with epithelial cells. Labeled vagal afferent fibers in the villous and cryptic lamina propria were found to be in intimate anatomical contact with fibrocyte-like cells that may belong to the class of interstitial cells of Cajal, and with small granular cells that might be granulocytes or histiocytes. Although our analysis was not quantitative, and considering that labeling was unilateral and not complete, it appears that the overall density of vagal afferent mucosal innervation was variable; many villi showed no evidence for innervation while other areas had quite dense networks of arborizing terminal fibers in several neighboring villi. Analysis of separate whole-mounted muscularis externa and submucosa peels revealed the presence of large bundles of labeled afferent fibers running within the myenteric plexus along the mesenteric attachment primarily in an aboral direction, with individual fibers turning towards the antimesenteric pole, and either penetrating into the submucosa or forming the characteristic intraganglionic laminar endings (IGLEs). Although the possibility of individual fibers issuing collaterals to myenteric IGLEs and at the same time to mucosal terminals was not demonstrated, it cannot be ruled out. These anatomical findings are discussed in the context of absorptive mechanisms for the different macronutrients and the implication of enteroendocrine cells such as CCK-containing cells that may function as intestinal "taste cells". PMID- 7771685 TI - Distribution of neurons of origin of zinc-containing projections in the amygdala of the rat. AB - The present study describes the distribution of neurons of origin of zinc containing pathways in the amygdaloid complex of the rat, using the selenium method for simultaneous retrograde labeling of all zinc-containing neurons. With this method, vesicular ionic zinc is precipitated intravitally with selenium compounds and transported retrogradely to the parent neurons, where it can be visualized by silver amplification. Neurons labeled retrogradely with silver amplified precipitate were observed in all amygdaloid nuclei except for the lateral olfactory tract nucleus, the accessory olfactory tract nucleus and the central nucleus. Very few labeled cell bodies were seen in the anterior amygdaloid area and the medial nucleus. The amygdalo-hippocampal area and the amygdalo-piriform transition area both showed a substantial number of labeled somata throughout their rostrocaudal extent. In the anterior cortical nucleus, very few labeled cell bodies were found in the rostral pole, whereas they were abundant in the caudal quarter of the nucleus. In the posterolateral cortical nucleus, the number of labeled cell bodies increased gradually; there were none in the rostral pole, but most of the neurons in the caudal part were labeled. The posteromedial cortical nucleus contained a great number of labeled somata, but with some variation in the rostrocaudal extent of the nucleus. Considerable numbers of labeled neurons were observed throughout the lateral nucleus. In the basolateral nucleus, a small number of labeled cell bodies was present in the rostral half, but a gradual increase was observed in the caudal direction. Finally, in the basomedial nucleus, very few labeled cell bodies were present in the rostral two-thirds, whilst a considerable number was encountered in the caudal one-third. Possible functional implications of neuronal zinc are considered. The distribution of neurons of origin of zinc-containing projections has been compared with previously described intrinsic connections of the rat amygdala, and tracts that may possibly be zinc-containing are outlined and discussed. It is concluded that in all probability a substantial proportion of the intrinsic connectivity of the rat amygdaloid complex is zinc-containing. PMID- 7771684 TI - Quantitative receptor autoradiography of eight different transmitter-binding sites in the hippocampus of the common marmoset, Callithrix jacchus. AB - The regional and laminar distributions of eight different transmitter-binding sites were measured in the marmoset hippocampus by means of quantitative in vitro receptor autoradiography. Receptors for 5-HT1, L-glutamate, N-methyl-D-aspartate (NMDA) and GABAA were similarly distributed. The highest concentrations of these receptors were found in the pyramidal layer of CA1 and the molecular layer of the dentate gyrus. The 5-HT2 receptors showed the highest concentrations in the oriens layer of CA2. The highest concentrations of muscarinic M1 receptors were seen in the pyramidal layer of CA1. Muscarinic M2 receptors were most densely concentrated in the pyramidal layers of CA1, CA2 and CA3. The noradrenergic alpha 1 receptors were most densely packed in the radiatum-lacunosum-molecular layer of CA2 and the molecular layer of the dentate gyrus. Statistically significant co distributions of serotoninergic, glutamatergic and GABAergic receptors point to possible interactions between these receptor systems in the same hippocampal regions and layers. Comparisons of marmoset distribution patterns for GABAA, NMDA, L-glutamate and 5-HT1 receptors with those in human hippocampi and those of other primates showed similarities between them. Clear differences in the patterns of alpha 1, M1, M2 and 5-HT2 receptors could be seen between marmoset and human hippocampi, indicating a high degree of species specificity in a presumably "conservative" brain region. More similarities, however, could be found between marmoset and human hippocampi than between those of rat and human brains, especially in relation to 5-HT1 and GABAA receptors and L-glutamate binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771686 TI - Comparison of the patterns of callosal connections in lateral parietal cortex of the rat, mouse and hamster. AB - In a recent study of the second somatosensory area (SmII) in the rat it was reported that the somatotopic map in the cortex lateral to the primary somatosensory area (SmI) is closely related to local features of the callosal pattern. The existence of this relationship suggests that knowledge of the overall pattern of callosal connections in the cortex lateral to SmI may facilitate the description of the somatotopic organization of lateral parietal cortex in other rodents. We tested this suggestion by comparing the callosal patterns in lateral parietal cortex in the rat, mouse and hamster. Our finding that the callosal pattern in the mouse closely resembles that in the rat supports the idea that the callosal pattern reflects the underlying somatotopy because the maps of SmII described previously in the mouse and rat are very similar to each other. In addition, on the basis of our observation that the callosal pattern in the hamster is very similar to that in the rat and mouse, we predict that these three rodent species share a common somatotopic plan in lateral parietal cortex. PMID- 7771687 TI - A time-dependent loss of retrograde transport ability in distally axotomized rubrospinal neurons. AB - Studies on the effect of axotomy on adult intrinsic central projection neurons have generally assumed that the severed proximal axonal stumps were still capable of retrogradely transporting tracer at varying times after injury. Failure of transport was interpreted as neuronal death, which is at odds with current understanding that central projection neurons survived distal axotomy. We used lumbar spinal cord-projecting rubrospinal neurons of the rat as a model to evaluate the ability of injured neurons to transport tracer retrogradely at different times after distal axotomy. We examined only the caudal part of the red nucleus, since rubrospinal neurons are concentrated here. In control animals, tracer applied to the rubrospinal tract at the T10 vertebral level labeled ventrolateral rubral neurons, while C3 application marked all rubral neurons. From 3 days after a T10 axotomy and tracer application, most ventrolateral neurons were no longer labeled by another tracer application at the C3 vertebral level via an axonal cut. The phenomenon was not caused by tracer toxicity, since a T10 tractotomy without tracer application also prevented these axotomized neurons from being labeled when treated similarly. Thus, neuronal retrograde transport capability was seriously retarded 3 days after a distal axotomy. Loss of retrograde transport may merely suggest that a mechanism no longer in service has been switched off, or perhaps it may insulate injured neurons from the effect of lesion site-derived factors. Using this property, we were able to localize cervical spinal cord-projecting rubrospinal neurons in the caudal red nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771688 TI - Distribution of GABA immunoreactivity in the retino-recipient layer of the viper optic tectum. A light and electron microscope quantitative study. AB - The distribution of GABA-immunoreactivity was investigated in the principal retino-recipient layer of the optic tectum in the snake Vipera aspis. This layer, the stratum griseum et fibrosum superficiale, contained an important proportion (approximately 50%) of small GABA-immunoreactive interneurons, characterized by a voluminous invaginated nucleus surrounded by a thin rim of cytoplasm poor in organelles and occasionally showing pleiomorphic synaptic vesicles, which could also be observed in some of the dendrites that contained synaptic vesicles. In the neuropile, the GABA-immunoreactive profiles containing synaptic vesicles could be subdivided into dendrites containing synaptic vesicles and axon terminals with pleiomorphic synaptic vesicles. The dendrites containing synaptic vesicles (23.4% of all profiles containing synaptic vesicles) were postsynaptic either to optic terminals (39.2%), GABA-immunoreactive axon terminals with pleiomorphic synaptic vesicles (48.2%) or to immunonegative (S1) boutons with round synaptic vesicles (12.6%). These dendrites were presynaptic to GABA immunoreactive (18%) neurons or immunonegative (82%) neurons. The axon terminals with pleiomorphic synaptic vesicles, which represented 47.4% of all profiles, were predominantly (99%) GABA-immunoreactive and four types could be distinguished according to cytological criteria. These axon terminals made synaptic contacts for the most part (78%) with immunonegative profiles, and more rarely (22%) with immunoreactive neurons. These data are compared to those previously obtained in the homologous structure of other vertebrate species, birds and mammals in particular. PMID- 7771689 TI - Expression of gap junction genes, connexin40 and connexin43, during fetal mouse development. AB - The expression patterns of the gap junction genes connexin40 and connexin43 have been analyzed during late mouse fetal development, i.e., at embryonic days 14.5 and 16.5, by in situ hybridization and immunofluorescence. Connexin40 was found in endothelial cells of vessels, cardiomyocytes and in developing myoblasts and myotubes. Expression of connexin40 in developing muscle fibers was strong in the back muscles and weaker in the muscles of the limbs. The number of labeled cells in the back muscle decreased with ongoing differentiation of myoblasts, in accordance with the idea that connexin40 is only expressed in the early stages of muscle cell differentiation. Within a muscle bundle, connexin40 expression was predominantly found at the outermost side where myoblasts fuse to multinucleated myotubes. In contrast, connexin43 exhibits a wide and complex pattern of expression in fetal mouse development. It is found in organs originating from all three germ layers, such as epidermis, heart, lung, muscle, kidney and gut. Connexin43 transcript and protein were very abundant in tissues that had been undergoing inductive interactions, e.g., the inner enamel epithelium of the teeth, the glomeruli of the kidneys and the infundibulum forming the neural part of the pituitary gland. Very high connexin43 expression was found in the embryonic meninges (dura mater) and in the fetal adrenal cortex. During keratinocyte differentiation connexin43 mRNA expression decreased, being much stronger in the stratum basale than in stratum granulosum. No obvious discrepancy between the amount of mRNA and protein of either connexin was noticed, suggesting that there is no specific translational regulation at these developmental stages. PMID- 7771690 TI - Measurement of upper airway pressures in exercising horses with dorsal displacement of the soft palate. AB - To determine whether abnormal airway pressures have a role in development of dorsal displacement of the soft palate (DDSP), measurements of tracheal and pharyngeal pressures were correlated with nasopharyngeal morphology in exercising horses. Exercising videoendoscopy and measurement of tracheal and pharyngeal pressures were used in 14 clinically normal horses and 19 horses with intermittent DDSP. The pressure signals were superimposed on the videoendoscope image, and both images were saved simultaneously on a videocassette for slow motion analysis to determine the instant displacement occurred in the respiratory cycle. Horses were submitted to an escalating 8-minute high-speed test with a maximal speed of 14 m/s. Compared with clinically normal horses, horses with intermittent DDSP did not have excessively negative inspiratory pressures during exercise. Eight horses displaced the soft palate during inspiration, 4 horses displaced it during expiration, and 7 displaced it by swallowing. Some horses displaced the soft palate at the beginning of the exercise trial, before reaching maximal speed, some horses displaced it at the peak speed, and some horses displaced it when slowing down. Epiglottic size in horses with DDSP was within normal limits, ruling out epiglottic hypoplasia as a cause of DDSP during exercise. Airway pressures were significantly (P < 0.002) altered after DDSP. Pharyngeal and tracheal inspiratory pressures were less negative, whereas pharyngeal expiratory pressure became less positive and tracheal expiratory pressure became more positive after displacement, suggesting a decrease in airflow and an increase in expiratory resistance in the upper airway. PMID- 7771691 TI - Arrhythmia prevalence during ambulatory electrocardiographic monitoring of beagles. AB - Ambulatory ECG, approximately 18 to 24 hours in duration, were obtained from 113 male and 115 female clinically normal, purpose-bred Beagles. The ECG analyzed semi-automatically (44 males, 46 females) were evaluated for heart rate, ventricular ectopic complexes (VEC), bradycardia, and sinus pause; those analyzed by visual inspection (69 males, 69 females) were evaluated for VEC, second-degree atrioventricular block, and supraventricular escape complexes. Mean heart rate was highest at times of maximal human contact (eg, feeding, cleaning) and lowest at periods of no human contact. Bradycardia was observed in 27 of 44 males (61.4%) and 18 of 46 females (39.1%). Sinus pause was identified in 33 of 44 males (75%) and 30 of 46 females (65.2%). Frequency of bradycardia and sinus pause tended to vary inversely with mean heart rate. Ventricular ectopic complexes were detected in 18.8 to 26.1% of the ECG analyzed by use of either method. Although VEC runs and bigeminy were observed, most VEC were single and occurred sporadically. Second-degree atrioventricular block was observed in 6 of 69 males (8.7%) and 14 of 69 females (20.3%); episodes often were single and occurred sporadically. Supraventricular escape complex occurred in 2 of 69 females (2.9%). Multiple types of abnormal complexes were observed in 2 of 69 males (2.9%) and 6 of 69 females (8.7%). Among clinically normal Beagles, ambulatory electrocardiography detects a higher percentage of dogs with VEC, second-degree atrioventricular block, and supraventricular ectopic complexes than does resting electrocardiography. PMID- 7771692 TI - Differential cell analysis and phenotypic subtyping of lymphocytes in bronchoalveolar lavage fluid from clinically normal dogs. AB - In 33 healthy dogs, 66 bronchoalveolar lavage samples from the right and left caudal lung lobes were analyzed for volume of return, cellularity, differential cellularity, and immunophenotypic lymphocyte subpopulations. Lavage return was 64.8% (mean) following 3 sequential 25-ml lavages, for a total lavage volume of 75 ml. With this technique, 21.1 x 10(6) cells/sample (mean) were obtained. The cellular components of bronchoalveolar lavage samples, in decreasing order of frequency, were alveolar macrophages (79.4%), lymphocytes (13.5%), eosinophils (3.6%), mast cells (2.1%), epithelial cells (0.8%), and neutrophils (0.6%). Mean alveolar lymphocyte subpopulation frequencies, determined in 18 samples, for pan T, CD4, and CD8 cells were 52, 21.9, and 17.8%, respectively, with a CD4/CD8 ratio of 1.3. Variables analyzed did not vary between right and left caudal lung lobes, nor were they affected by body weight. PMID- 7771693 TI - Magnetic resonance arthrography of the scapulohumeral joint in dogs, using gadopentetate dimeglumine. AB - Six scapulohumeral joints (3 normal joints and 3 joints with radiographic evidence of osteochondrosis) underwent conventional magnetic resonance (MR) imaging and MR scapulohumeral arthrography to evaluate delineation of the articular cartilage. The MR arthrography was performed, using 5 ml of 500 microM gadopentetate dimeglumine (Gd-DTPA) as a contrast medium. Delineation of normal articular cartilage and cartilage defects was less accurate after intra-articular administration of Gd-DTPA. Therefore, it was concluded that MR arthrography with Gd-DTPA is unrewarding for evaluation of osteochondrosis lesions. PMID- 7771695 TI - Simultaneous identification and determination of residual penicillins by use of high-performance liquid chromatography with spectrophotometric or fluorometric detectors. AB - Using 7 penicillins (amoxicillin, ampicillin, methicillin, penicillin G, oxacillin, cloxacillin, and dicloxacillin), simultaneous and direct determination of residual penicillins in biological samples was carried out by use of bioassay and high-performance liquid chromatography with spectrophotometric or fluorometric detectors. By use of assay medium seeded with penicillin-sensitive Micrococcus luteus (ATCC No. 9341) as a test organism, we were able to detect penicillins even at low concentrations. All penicillins treated with 10 U of penicillinase/ml did not produce inhibition zones by disk testing, even at a concentration of 100 micrograms of penicillin/ml/assay plate. Using a mobile phase of acetonitrile:methanol: 0.01M KH2PO4 (19:11:70, v/v/v; pH, 7.1), standard solutions of the penicillins were separated from each other by use of high performance liquid chromatography analysis, producing symmetric peaks without tailing, each of which had a characteristic retention time. Simultaneous detection of residual penicillins in bovine serum, kidneys, and liver, for the 5 penicillins for which analysis was possible by use of the UV method, yielded recovery rates from 71.4 to 102.3%; for the 2 amino-penicillins, amoxicillin and ampicillin, which could only be detected by use of the fluorometric method, recovery rate ranged from 72.9 to 103%. PMID- 7771694 TI - Development of methods for analyzing plasma lipoprotein concentrations and associated enzyme activities and their use to measure the effects of pregnancy and lactation in cats. AB - Methods available for measurement of plasma lipoprotein-cholesterol concentrations and activities of lipoprotein lipase, hepatic lipase, lecithin:cholesterol acyl transferase (LCAT), and cholesteryl ester transfer protein were adapted for use in cats. A combined ultracentrifugation/precipitation procedure was used to isolate very low-density lipoproteins (VLDL), then to separate low-density lipoproteins (LDL) from high density lipoproteins (HDL). The reagent used, 92 mM heparin-manganese chloride, provided complete precipitation of LDL with only trace and insignificant contamination by HDL. Efforts to selectively measure lipoprotein lipase activity in plasma, collected after IV injection of heparin, by inhibiting hepatic lipase with sodium dodecyl sulfate were unsuccessful, and the activity of this enzyme was calculated as the difference between total and hepatic lipase activities. The latter was measured in the presence of high salt concentration to inhibit lipoprotein lipase. Cholesterol esterifying activity was identified in feline plasma and was typical of LCAT, in that it was dependent on apolipoprotein A-I as a cofactor. The intra-assay and interassay coefficients of variation for measurement of lipoprotein lipase, hepatic lipase, and LCAT activities were 18.4, 4.6, and 7.2%, and 20.4, 10.7, and 5.3%, respectively. Appreciable cholesteryl ester transfer protein activity was not detected in either undiluted or diluted plasma. These methods were subsequently used to investigate the effects of pregnancy and lactation on lipoprotein metabolism in a group of 10 queens. Plasma concentrations of cholesterol and triglycerides were unaltered during pregnancy, but the concentrations of VLDL-cholesterol increased and those of HDL-cholesterol decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771696 TI - Effects of storage on serum ionized calcium and pH values in clinically normal dogs. AB - The stability of ionized calcium (CaI) concentration and pH in sera (n = 14) stored at 23 or 4 C for 6, 9, 12, 24, 48, or 72 hours, or -10 C for 1, 3, 7, 14, or 30 days was evaluated. Also studied were the effects of oxygen exposure, cold handling, and feeding on CaI and pH values. Results indicated that serum CaI concentration was stable throughout 72 hours of storage at 23 or 4 C, and for 7 days at -10 C. Serum CaI concentration significantly (P < 0.05) decreased by 14 days of storage at -10 C. Serum pH was stable for 6 hours at 23 or 4 C, and for 24 hours at -10 C, but significantly (P < 0.05) increased by 9 hours of storage at 23 or 4 C and by 3 days at -10 C. Exposure of the surface of the serum to air immediately before measurement had no effect on CaI or pH values, but mixing serum with air resulted in significantly (P < 0.05) decreased CaI concentration and increased pH. Handling of blood on ice resulted in significantly (P < 0.05) higher serum pH, compared with blood handled at 23 C, but serum CaI concentration was unaffected. Serum obtained at 2 hours after feeding did not have any significant changes in CaI, total calcium, or pH values. It appears that if canine serum is obtained, handled, and stored anaerobically, CaI concentration can be accurately measured after 72 hours at 23 or 4 C, or after 7 days at -10 C. PMID- 7771697 TI - Application of pulsed-field gel electrophoresis for differentiation of vaccine strain RB51 from field isolates of Brucella abortus from cattle, bison, and elk. AB - Restriction endonuclease patterns of genomic fragments separated by use of pulsed field gel electrophoresis were used to differentiate Brucella abortus strain RB51, a rifampin-resistant mutant of the standard virulent strain 2308, from other brucellae. Results were compared with results obtained by use of standard methods for characterizing brucellae. Electrophoretic patterns of the ATCC type strains allowed identification of the strains to the level of species. Genomic profiles of B abortus biovars 1, 2, and 4 were similar, as were those of biovars 5, 6, and of biovar 3 was similar to that of biovars 5, 6, and 9, except for a missing band at 93 kb and additional bands at 65 and 67 kb. A different fingerprint was detected in B abortus strain RB51, using the pulsed-field gel electrophoresis patterns of genomic DNA digested with restrictive endonuclease Xba I. The profile of B abortus strain RB51 contained a band at 104 kb, as opposed to a 109-kb fragment within profiles of B abortus isolates from naturally infected cattle, bison, and elk. Despite known biochemical and biological differences between RB51 and its parent strain (2308), restriction endonuclease analysis results were similar. PMID- 7771699 TI - Antiphagocytic properties of uterine isolates of Streptococcus zooepidemicus and mechanisms of killing in freshly obtained blood of horses. AB - A total of 22 clinical streptococcal isolates, predominantly Streptococcus zooepidemicus, associated with endometritis in horses were tested for their ability to withstand the natural bactericidal properties of freshly obtained blood. During a 3-hour incubation in blood from a single horse, 8 of these isolates survived and grew, the remainder were killed. To determine whether this ability to grow extended to blood of other horses, 5 of these growing isolates were tested for their ability to grow in the blood of 5 additional horses. The same 5 horses were used for each isolate. The isolates grew in blood of some of the horses, but were killed in blood of the others. However, the horse's blood that mediated killing was different for each isolate. Killing required leukocytes, but the specificity for killing appeared to reside in plasma, although plasma by itself was not bactericidal. Heat-stable and heat-labile components in plasma, interpreted as antibody and complement, respectively, appeared necessary for killing. Isolates that could grow in fresh blood lost this ability after 10 passages in artificial media. Results of these experiments of phagocytosis in fresh blood may provide helpful insights into the phagocytosis of S zooepidemicus in equine uterine fluid. PMID- 7771698 TI - Administration of recombinant human interleukin 1 receptor antagonist during endotoxin-induced mastitis in cows. AB - The role of interleukin 1 (IL-1) as an inflammatory mediator during mastitis and the therapeutic effect of recombinant human IL-1 receptor antagonist (IL-1ra) for bovine mastitis was studied. Cows were intramammarily infused with lipopolysaccharide (25 micrograms) in 1 mammary gland. Half the cows also received infusions of 5 mg of IL-1ra into the same mammary gland just prior to endotoxin infusion and 4, 8, and 12 hours later. After endotoxin infusion, tumor necrosis factor and high IL-1 bioactivity were detected in whey from infused glands. Vascular permeability changes and neutrophil accumulation in milk paralleled the appearance of cytokines. A systemic reaction, characterized by pyrexia and an increase in blood cortisol concentration, also were observed. Milk yield was inhibited and milk composition was altered in infused and noninfused glands. The increase in IL-1 bioactivity in milk after endotoxin infusion was almost completely prevented in glands receiving IL-1ra. However, IL-1ra had no effect on local inflammation, systemic reaction, or impairment in productive performance. These results indicate that IL-1 does not mediate its effect within the milk compartment, and suggest either that IL-1 is not critical to the mastitic response or that intramammary infusion of IL-1ra does not place the antagonist where IL-1 interacts with its receptor. PMID- 7771700 TI - Diet effect on activity product ratios of uric acid, sodium urate, and ammonium urate in urine formed by healthy beagles. AB - Urine activity product ratios of uric acid, sodium urate, and ammonium urate and urinary excretion of metabolites were determined in 24-hour samples produced by 6 healthy Beagles during periods of consumption of a low-protein, casein-based diet (diet A) and a high-protein, meat-based diet (diet B). Comparison of effects of diet A with those of diet B revealed: significantly lower activity product ratios of uric acid (P = 0.025), sodium urate (P = 0.045), and ammonium urate (P = 0.0045); significantly lower 24-hour urinary excretion of uric acid (P = 0.002), ammonia (P = 0.0002), sodium (P = 0.01), calcium (P = 0.005), phosphorus (P = 0.0003), magnesium (P = 0.01), and oxalic acid (P = 0.004); significantly (P = 0.0001) higher 24-hour urine pH; and significantly (P = 0.01) lower endogenous creatinine clearance. These results suggest that consumption of diet A minimizes changes in urine that predispose dogs to uric acid, sodium urate, and ammonium urate urolithiasis. PMID- 7771701 TI - Prophylactic effect of dietary zinc in a laboratory mouse model of swine dysentery. AB - Reduced prevalence of diarrhea and mortality has been reported after dietary supplementation with zinc compounds in swine with naturally acquired colibacillosis and those challenge-exposed with Serpulina hyodysenteriae; however, the usefulness of this approach for control of enteric diseases of swine remains to be determined. To examine the effect of dietary zinc-containing compounds on the colonization and development of cecal lesions associated with S hyodysenteriae infection, a defined diet alone or with added ZnO, ZnSO4, or Zn methionine complex to a final concentration of approximately 6,000 mg of Zn2+/kg of complete feed was fed ad libitum to 156 female mice (strain C3H/HeN) for 10 days prior to oral inoculation either with S hyodysenteriae or sterile trypticase soy broth. Rations were continued for 42 days, while at weekly intervals, 3 mice/group were necropsied for determination of body weight, cecal weight, liver zinc concentration, presence of S hyodysenteriae in the cecum, and gross and histologic assessments of cecal lesions. From postinoculation day 0 to 42, the liver zinc concentration of mice fed the zinc-supplemented diets was approximately twice that of mice fed the basal diet, irrespective of the source of zinc. From postinoculation day 7 through 42, the overall recovery rate of S hyodysenteriae in infected mice fed the basal diet was 77.8%. In contrast, recovery rates of S hyodysenteriae from S hyodysenteriae-inoculated mice fed the zinc-supplemented diets were 0% for Zn-methionine and ZnO and 16.7% for ZnSO4. Mice fed the basal diet had significantly (P < 0.05) higher weight gain than mice fed the zinc-supplemented diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771703 TI - Histochemical and morphometric study of fiber types in ten skeletal muscles of healthy young adult cats. AB - A histochemical and morphometric study of fiber types in a variety of skeletal muscles of healthy young adult cats was undertaken to provide normative data not available previously. Using a standardized system of nomenclature, fiber types 1, 2A, 2B, and 2C were identified in most cat muscles on the basis of myosin ATPase staining at pH 4.45. Type-2M fibers were present in temporalis (TEM) and masseter (MAS) muscles. Type-1 fibers predominated in medial head of triceps (MHT) and soleus muscles. Type-2B fibers were dominant in biceps femoris, lateral head of gastrocnemius cranial tibial, long head of triceps, and superficial digital flexor muscles; type-2A fibers were dominant in buccinator muscle samples; and type-2M fibers were dominant in TEM and MAS muscles. Numbers of type-2C fibers did not exceed 2 to 3% of the myofiber population in any muscle. In CT and LHT muscles, a gradient of fiber type distribution was observed, with significant (P < 0.05) increase in numbers of type-1 and type-2A fibers in deeper regions of the muscles. The distribution of fiber types was compartmentalized in MHT and MAS specimens. Diameter of type-2B fibers was significantly (P < 0.05) larger than that of type-1 and type-2A fibers in biceps femoris, lateral head of gastrocnemius, cranial tibial, long head of triceps, and superficial MHT muscles. Diameter of type-2M fibers was significantly (P < 0.05) larger than that of type 1 fibers in TEM and MAS muscles. The soleus type-1 muscle fibers were the largest fibers encountered in any muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771702 TI - Changes in the intestinal mucosal cell populations of German shepherd dogs fed diets containing different protein sources. AB - Sixteen German Shepherd Dogs from 4 litters were IgA-deficient on the basis of at least 1 of 2 serum IgA determinations, and all had small intestinal bacterial overgrowth, as documented by quantitated small intestinal bacterial culture in another study. These dogs were fed 2 diets that differed principally in their protein source (chicken vs beef, milk, and wheat). All dogs were fed each diet for 2 weeks before the study began. Next, all dogs were fed the chicken-based diet for 2 months. Then, half the dogs (group 1) were randomly assigned to continue eating the chicken-based diet, while the other half (group 2) ate a diet containing beef, milk, and wheat proteins. The small intestine was biopsied at the beginning of the study and after dogs had eaten the assigned diet for 2 and 4 months. At 2 months, group-2 dogs had more colonic mucosal mast cells, but this difference did not persist at 4 months. At the end of the study (ie, 4 months), although all dogs were clinically normal, group-2 dogs had significantly (P = 0.010) decreased numbers of jejunal villus plasma cells. However, these histologic changes were not considered clinically important. There were no significant differences in blood eosinophil counts, serum trypsin-like immunoreactivity, or cobalamin, folate, or IgA concentration. Clinical differences were not detected between the 2 groups, before or after the study. Changes were seen in serum IgM and IgG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771704 TI - Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses. AB - Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours after administration of the drug, bile concentrations of GLUC were high compared with those in plasma and enantioselectivity favored S-GLUC. These data indicate that the higher body clearance observed for S-CPF is a consequence of the enantioselectivity in liver glucuronidation and subsequent biliary excretion of the S enantiomer of the drug. PMID- 7771705 TI - Impact of age-related alteration of plasma alpha 1-acid glycoprotein concentration on erythromycin pharmacokinetics in pigs. AB - Erythromycin (EM) pharmacokinetic variables were studied after IV administration of the drug (10 mg/kg of body weight) to 1-, 6-, and 15-day-old pigs. With advancing age, from 1 day to 15 days after birth, half-life of EM became shorter (3.0 hours to 1.4 hour), whereas apparent volume of distribution, total body clearance (CLt), and intrinsic clearance became greater: 0.68 to 3.28 (L/kg), 0.15 to 1.42 (L/h/kg), and 1.81 to 3.56 (L/h/kg), respectively. The percentage of plasma protein binding of EM decreased from 91 to 56%, correlating well with volume of distribution and CLt values. The altered binding percentage depended on plasma alpha 1-acid glycoprotein (AGP) concentration, but not on albumin concentration. With advancing age, plasma AGP concentration was markedly decreased from approximately 6,000 micrograms/ml to 700 micrograms/ml. Despite a twofold increase in intrinsic clearance with advancing age, CLt increased ninefold, implying that the decreased protein binding contributed to the increase of CLt more preferentially than did maturational development of elimination capacity. Therefore, the altered protein binding of EM attributable to the change in plasma AGP concentration could be a major causal factor of the age-related pharmacokinetic variables of EM in pigs. PMID- 7771706 TI - Regulation of respiratory muscle activities during chemoreceptor stimulation in adult horses. AB - We examined the electromyographic activity of the costal portion of the diaphragm and the transverse abdominal and external oblique muscles in 6 chronically instrumented awake adult horses during eupneic breathing, during 2 levels of hypercapnia (fractional concentration of inspired CO2; FICO2 = 0.4 and 0.6), and during 2 levels of hypocapnic hypoxia (FIO2 = 0.15 and 0.12). Using the inert gas technique, we also measured the end-expiratory lung volumes of the 6 horses during eupnea, 6% CO2 challenge, and 12% O2 breathing. During eupneic breathing, phasic electrical activity of these 3 muscles was always present and was preceded by the onset of mechanical flow. At progressive levels of hypercapnia, the magnitude of inspiratory and expiratory electrical activity increased, and for the expiratory muscles, this recruitment coincided with significant (P < 0.05) increases in peak expiratory gastric pressure. However, during hypocapnic hypoxia, differential recruitment patterns of the respiratory muscles were found. The electrical activity of the diaphragm increased in magnitude and occurred sooner relative to the onset of mechanical flow. The magnitude and onset of abdominal expiratory activity failed to increase significantly during these episodes of hyperpnea and this pattern of activity coincided with decrements in peak expiratory gastric pressure. Despite alterations in muscle recruitment patterns during these hyperpneic episodes, end-expiratory lung volume remained unchanged. Thus, we conclude that adult horses respond similarly to awake dogs during peripheral and central chemoreceptor stimulation. PMID- 7771707 TI - Quantitative electroencephalographic evaluation to determine the quality of analgesia during anesthesia of horses for arthroscopic surgery. AB - We compared the anesthetic combination of detomidine, ketamine, and halothane in control horses not undergoing apparently painful procedures with that in horses during arthroscopic surgery. The effectiveness of this regimen in suppressing neurologic response to surgery was, thus, evaluated. In this study, significant differences were not observed in electroencephalographic total amplitude, spectral edge, or beta-to-delta frequency ratio between surgically treated and nonsurgically treated (control) horses. On the basis of its attenuation of encephalographic responses, we conclude that detomidine (20 micrograms/kg of body weight, IV) and ketamine (2.2 mg/kg, IV) induction of anesthesia followed by maintenance with halothane is an effective regimen for control of pain in horses during arthroscopic surgery. The insignificant frequency changes observed without any other signs of inadequate anesthesia or pain may indicate a surgical stress response. We hypothesize that brain activity monitoring may give an earlier index to initiation of surgically induced stress than do hormonal responses, because endocrine alterations are not as rapidly perceived as is the electroencephalogram. Analysis of spectral edge frequency changes could be used to evaluate anesthetic regimens to find those that cause the least stress to the CNS during surgery in horses. Differences in species responses to an anesthetic agent or the regimen's effectiveness in prevention of pain during surgery may be identified by adoption of the study model. Evaluation of cardiopulmonary variables during anesthesia, with and without surgery, did not reveal any alterations that would be relevant to CNS responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771708 TI - Parathyroid hormone-related protein and calcium homeostasis during the periparturient period of dairy cows. AB - Plasma and milk concentrations of parathyroid hormone-related protein (PTHrP) at various stages of pregnancy and lactation were determined in thirty-nine 3- to 16 year-old Brown Swiss and Red Holstein x Simmental dairy cows originating from 4 herds. Eighteen of the cows were separated into 2 groups: low-parity (LP, n = 8) cows if they were in their first or second pregnancy and high-parity (HP, n = 10) cows if they were in their third or greater pregnancy. Blood samples were collected from each cow on 1 occasion, 15 to 5 days before calving, and blood and milk samples were collected daily during 6 days after calving. Serum total and ionized calcium (Ca(tot) and Ca2+, respectively) and milk Ca(tot) concentrations were also quantified. A transient postpartum decrease of serum Ca(tot) and Ca2+ concentrations was observed, whereas milk Ca(tot) concentration was constant. Plasma concentration of PTHrP was detected in 11 of 21 cows by use of an immunoradiometric assay (range, 0.45 to 1.82 pmol/L). Daily mean (+/- SD) colostrum and milk PTHrP concentrations ranged from 3.25 (+/- 3.23) to 4.69 (+/- 1.36) nmol/L in LP cows and 2.74 (+/- 0.5) to 5.95 (+/- 0.33) nmol/L in HP cows. In all cows of the HP group and most cows of the LP group, milk PTHrP concentration was highest in the day-1 sample. Milk PTHrP concentration correlated positively with milk Ca(tot) concentration in HP cows (r = 0.5959, P < 0.0001). In contrast, there was a negative relation between milk PTHrP and milk Ca(tot) concentrations in LP cows (r = -0.3285, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771709 TI - Enrofloxacin concentrations in dogs with normal prostate and dogs with chronic bacterial prostatitis. AB - Chronic Escherichia coli-associated prostatitis was induced in 16 dogs; 9 noninfected dogs served as controls; and all dogs were vasectomized. Two to 3 weeks after instillation of bacteria directly into the prostate, the urine or prostatic fluid or both from 13 of 16 dogs were culture positive. Enrofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to all dogs during the third or fourth week after surgery, at a dosage of approximately 5 mg/kg of body weight, every 12 hours for 7 days. Serum and prostatic fluid concentrations of enrofloxacin were concurrently measured in all dogs on days 2, 4, and 6 at 2 hours after dosing. Serum and prostatic tissue concentrations of enrofloxacin were concurrently measured in all dogs on day 7, at 1.5, 3, 4.5, and 6 hours after dosing. When values for these samples were compared, using a two-factor ANOVA, significant differences were not found. Use of this dosing regimen of enrofloxacin resulted in prostatic fluid and prostatic tissue concentrations exceeding the minimum inhibitory concentration of most pathogens that cause bacterial prostatitis. In addition, prostatic fluid-to-serum and prostatic tissue to-serum concentration ratios were greater than 1.0. PMID- 7771710 TI - Comparison of volume-conducted far-field short-latency glossopharyngeal nerve evoked potentials recorded from the scalp with similarly obtained near-field potentials from the solitary nucleus in dogs. AB - In 11 dogs, potentials recorded from the scalp and from the solitary nucleus after stimulation of the glossopharyngeal nerve were compared. The far-field potentials recorded from the scalp consisted of negativity, with peak latency of 2.10 to 3.45 milliseconds (mean, 2.93 milliseconds), followed by positivity, with peak latency of 3.20 to 5.95 milliseconds (mean, 4.86 milliseconds) and duration of 4.65 to 6.95 milliseconds (mean, 5.70 milliseconds). The near-field potentials recorded from the solitary nucleus consisted of positivity, with peak latency of 2.15 to 2.70 milliseconds (mean, 2.45 milliseconds), followed by negativity, with peak latency of 4.05 to 5.05 milliseconds (mean, 4.39 milliseconds) and duration of 4.45 to 5.80 milliseconds (mean, 5.21 milliseconds). Comparison of the far field potentials (n = 10) with the near-field potentials (n = 5) indicated that polarity of the waves was reversed and that the first peak's latency was slightly (approx 0.5 milliseconds) longer in the scalp-recorded far-field potentials. Neither the difference in latency of the second peak nor the difference in its duration, measured from the onset of the potentials to the return to the baseline of the activity, was significant. The results strongly suggest that the response in the solitary nucleus evoked by electrical stimulation of the glossopharyngeal nerve is the source of at least part of the scalp-recorded responses to stimulation of the same nerve. The scalp-recorded far-field potentials could, therefore, be characterized as volume conducted from the evoked response in the solitary nucleus. PMID- 7771711 TI - Bioequivalency comparison between two gonadotropin-releasing hormone products. AB - The bioequivalency of 2 gondatropin-releasing hormone (GnRH) preparations, gonadorelin diacetate tetrahydrate and gonadorelin semicarbonate, was compared on the basis of luteinizing hormone (LH)-releasing ability of the 2 products in diestrous dairy cows. Twenty-four cycling, nonlactating Holstein cows were subjected to a double prostaglandin estrus synchronization treatment to simultaneously control stage of the estrous cycle and time factors as potential variables effecting LH responses to the treatments being studied. Circulating progesterone concentration was determined to verify stage of cycle at strategic times throughout the study. Twelve days after the second prostaglandin treatment, all cows were randomly assigned to 1 of 2 groups (n = 12). Each group of 12 cows received single doses (100 micrograms) of either GnRH preparation at the start of each test period in a 2-period crossover design. Serum samples were obtained prior to and at 12 times (10, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1,440 minutes) after treatment and were assayed to determine circulating LH concentration. Significant difference between the 2 GnRH products was not found with respect to: mean concentration of LH in the blood during the 24 hours after treatment; maximal LH concentration; time from treatment to maximal LH concentration; and area under the LH concentration curve from time 0 through each of 7 times after treatment (0.5, 1, 1.5, 2, 4, 8, and 24 hours). These data confirm the bioequivalency of the 2 GnRH products. PMID- 7771712 TI - Gender differences in cancer of the larynx. AB - Gender differences in the incidence and mortality rates for cancers of the lung, colon, and larynx have previously been noted. The goal of this project was to identify gender differences in prognostic variables for survival and recurrence for patients with cancer of the larynx. The medical records of 193 patients with cancer of the larynx treated initially between 1973 and 1985 were examined retrospectively. A total of 151 men and 42 women were included. A majority of men developed glottic cancers, whereas a majority of women developed supraglottic cancers. Age was prognostically important for both genders; however, comorbidity, symptom severity, anatomic subsite, and TNM stage all had different impacts on survival and recurrence in men and women. No gender difference in initial treatment was found. This study suggests that when designing and analyzing the results from clinical studies of cancer of the larynx, it is important to employ stratification based on gender. PMID- 7771713 TI - Three-dimensional imaging of the hypopharynx and larynx by means of helical (spiral) computed tomography. Comparison of radiological and otolaryngological evaluation. AB - A new computed tomography (CT) technology, helical (spiral) CT, allows the entire neck to be imaged in only 30 seconds. Although multiplanar and three-dimensional (3-D) imaging could be performed with conventional CT, the volumetric acquisition provided by helical (spiral) CT allows significantly improved quality and easier reconstruction for more applications. These 3-D models show an airway appearance similar to that obtained with laryngography. Independent review of the 3-D images in 12 patients with lesions by two radiologists and one otolaryngologist was performed to assess 1) image quality, 2) ability to judge lesion extent, and 3) assistance in understanding the lesion compared to that provided by routine axial scans. Rating scores of 1 to 5 were assigned, with 5 representing the best quality or greatest value. The results showed that both groups scored image quality equally: 4.7. Lesion extent for the radiologists was 2.6, while the otolaryngologist's ranking was 3.7 (p < .01). In assisting understanding of lesions versus axial scans, radiologists ranked 3-D images 2.1, while the otolaryngologist ranked them 3.1 (p < .01). In summary, 3-D models provide a complementary imaging technique in understanding upper airway disease. PMID- 7771714 TI - Laser aryepiglottoplasty for the treatment of neurasthenic laryngomalacia in cerebral palsy. AB - Patients with cerebral palsy usually suffer from lack of coordination in the neuromuscular mechanism in their upper airway and digestive tract. Difficulty in swallowing and aspiration are common problems in these patients, and stridorous breathing sometimes develops as a secondary symptom. Laryngoscopic examination revealed that redundant tissue in the aryepiglottic fold area was the cause of stridor and upper airway obstruction in four patients with cerebral palsy. We report on these four patients in whom laser reduction of the redundant mucosa led to dramatic improvements in stridor. Secondary benefits to family members and others were equally impressive. PMID- 7771715 TI - Treatment of vocal fold immobility by glutaraldehyde-cross-linked collagen injection: long-term results. AB - Fifty-three cases of unilateral vocal fold immobility treated by glutaraldehyde cross-linked (GAX) collagen over a 6-year period with a mean follow-up of 4.5 years were reviewed for assessment of the immediate and long-term effects on phonation. The mean amount injected was 1.47 mL. No long-term local or systemic reaction to the collagen was seen. The median preoperative maximum phonation time (MPT) was 7.5 seconds, the median immediate postoperative MPT 12 seconds, and the median long-term postoperative MPT 11 seconds. The median preoperative phonatory quotient (PQ) was 564 mL/s. The median immediate postoperative PQ was 320 mL/s, whereas the median long-term postoperative PQ was 385 mL/s. The quantitative improvement in the voice as measured by the PQ was thus 67% for the short range and 49% for the long range. The decline in the results over time was 20.3%. Vocal frequency analysis showed that the fundamental frequency and harmonics returned and were maintained in the long term for more than 80% of the patients with the help of speech therapy. This relative stability is explained by the findings of previous histological work. The fact that collagen, unlike Teflon, does not cause an inflammatory reaction and the partial maintenance of the improvement achieved, which is to be compared with the instability of the effects produced by resorbable substances, make it the "least objectionable" injectable for the treatment of unilateral glottic fold immobility. One must overcompensate 20% to 30%, given the results of the long-term stability studies. PMID- 7771716 TI - Factors influencing regional lymph node metastasis from laryngeal carcinoma. AB - A series of 103 cases of laryngeal carcinoma subjected either to a unilateral or to a bilateral comprehensive neck dissection was reviewed with reference to risk factors influencing regional lymph node metastasis. The sensitivity of clinical examination was only 67.4%, while the specificity was 88.3%. Most metastases were in the upper and middle jugular chain of nodes (levels 2 and 3). Only patients with positive nodes at levels 2, 3, and/or 4 had histologically positive nodes at levels 1 or 5. Selected demographic, clinical, and pathologic variables were analyzed with respect to their potential predictive value regarding the risk of histologically proven neck node metastasis. Logistic regression analysis demonstrated that tumor site and histologic grade were the most important predictors of lymph node metastasis. Considering only NO cases, the likelihood of occult metastasis was significantly affected exclusively by tumor site (higher risk for supraglottic lesions). PMID- 7771717 TI - Effect of magnetic resonance imaging on implantable eyelid weights. AB - Implanted upper eyelid gold weights are used to prevent corneal injury in patients with facial nerve paralysis. Some of these individuals require postoperative radiographic surveillance for recurrent lateral skull base disease. Magnetic resonance imaging (MRI) provides the most accurate radiologic assessment; however, there is concern about the safety of performing MRI in patients with any metallic implant. Potential risks include local tissue heating and implant migration. Gold weights of 0.8 and 1.4 g were placed in an open chamber and were exposed to a magnetic field of 1.5 T. There was no measurable motion or displacement of the weights. The results were similar in 6 rats in which gold weights were subcutaneously implanted. Additionally, histologic examination of the implant sites revealed no adverse tissue effects attributable to MRI-generated heating of the implants. When carbon steel implants in the rat model were subjected to the magnetic field, there was no displacement of the implants and no adverse tissue effects were noted, despite the fact that a carbon steel implant in an open chamber demonstrated significant migration. The absence of motion of the gold weight implants combined with the lack of adverse tissue effects suggests the relative safety of performing MRI in patients with previously placed gold weights as upper eyelid implants. PMID- 7771718 TI - Eustachian tube function of patients with nasopharyngeal carcinoma. AB - Prolonged observations of the eustachian tube (ET) function were made on 40 ears of 20 patients with nasopharyngeal carcinoma (NPC) who survived more than 5 years after radiotherapy in a state of remission. The ET function tests included passive opening, inflation-deflation, and clearance, and were performed before, at 6 months, and at 5 years after radiotherapy. The test results were found to be worst at 6 months after radiotherapy and improved at 5 years after radiotherapy. Tubal obstruction and inflammation are the main causes of the ET malfunction that results in otitis media with effusion (OME) in NPC patients after radiotherapy. Insertion of a ventilation tube into the ear with OME can relieve tubal obstruction but can aggravate inflammation. Thus, myringotomy and aspiration of effusion and local treatment may be preferable to insertion of a ventilation tube in NPC patients with OME. When hearing improvement in prolonged survival of NPC patients with OME is needed, the use of amplification is recommended. PMID- 7771719 TI - Evoked otoacoustic emissions and electrocochleography in a patient with multiple sclerosis. AB - A 24-year-old woman with multiple sclerosis had right-sided hearing impairment with tinnitus. She underwent electrocochleography (ECochG) and examination of evoked otoacoustic emissions (EOAEs) to assess cochlear function. An acoustic probe to measure EOAEs was inserted into the external ear canal. The ECochG action potential and cochlear microphonics were recorded by a transtympanic needle electrode technique. Both fast and slow components of EOAEs appeared in either the period of deteriorated hearing acuity or when it was improved. They showed normal detection thresholds and input-output curves during both periods. Cochlear microphonics with almost normal detection thresholds and input-output functions were obtained during the period of deteriorated hearing acuity. Action potential (N1) input-output curves during relapse with hearing loss were notably lower in amplitude and longer in latency than those obtained at the time hearing impairment showed improvement. The EOAE and ECochG findings suggested that this patient had almost normal cochlear function, and we assumed from the magnetic resonance imaging and auditory brain stem response findings as well as the ECochG that the hearing impairment was caused by dysfunction of auditory pathways in the brain stem, including structures that contribute to generation of the N1 potential of the ECochG. PMID- 7771720 TI - Bone resorption in human cholesteatoma: morphological study with scanning electron microscopy. AB - The detailed mechanism of bone resorption in cholesteatoma was investigated by means of eroded ossicles obtained during middle ear surgery for cholesteatoma. In the light microscopic study, multinucleate osteoclasts with ruffled borders were found in contact with the eroded bone, which appeared to be osteoclastic lacunae. Scanning electron microscopy revealed the lacunae to be many absorption bays, 30 to 100 microns in diameter, clustered on the surface of eroded areas. Numerous cone-shaped stubs of digested collagen fiber bundles, consisting of scores of collagen fibrils and degenerated extracellular organic substances, were visible at higher magnification on the bottom of the absorption bay. The pattern of fusion and twining of the disarranged collagen fibrils at the top of the partly digested fiber bundles was clearly rendered by the alkali-water maceration method for scanning electron microscopy. We infer from the morphological evidence that osteoclastic resorption may be one of the major mechanisms of bone destruction in cholesteatoma, and that demineralization and degeneration of extracellular organic substances precede disruption of collagen fibrils at the front of bone resorption. PMID- 7771721 TI - Postnatal development of the internal auditory canal studied by computer-aided three-dimensional reconstruction and measurement. AB - Postnatal development of the internal auditory canal (IAC) was investigated in 20 normal human temporal bones obtained from individuals 1 month to 72 years old. Computer-aided three-dimensional reconstruction and measurement of bones showed that the superior, inferior, anterior, and posterior walls of the IAC lengthen significantly from birth until about 10 years of age, with development mainly attributable to lengthening of the part of the IAC medial to the foramen singulare. The lengths of the part of the IAC lateral to the foramen singulare and of the transverse crest and Bill's bar did not appear to develop postnatally. The IAC diameter increased slightly at the porus for about the first year after birth, but not at the fundus or the middle portion of the canal. This finding was confirmed by studying the shape of the IAC. Postnatal increases in the volume of the IAC followed patterns similar to that of increases in length of studying the shape of the IAC. Postnatal increases in the volume of the IAC followed patterns similar to that of increases in length of the IAC walls. These results show that postnatally the IAC increases significantly in length until about 10 years of age and slightly in diameter until about 1 year of age, especially medial to the foramen singulare. This concentration of growth of the IAC medially implies that its postnatal development is mainly due to growth of the bone around the otic capsule, which has implications for IAC surgery. PMID- 7771723 TI - Recovery of caloric function in experimental perilymph fistula. AB - Twenty of 46 guinea pigs with experimental perilymph fistula that showed canal paresis on an ice water caloric test during the first week after operation were studied on the following days to observe the progression and final outcome of the caloric test. Two weeks after operation, 12 animals showed persistent canal paresis, whereas 8 animals developed a normal caloric response. Resolution of the caloric response progressed from canal paresis, via caloric irregularity, to a final return of normal caloric response. Morphological study of animals with recovery of caloric function shows healing of the previously ruptured membrane, with preservation of the contour of the membranous labyrinth in the lateral semicircular duct, and intact sensorineural elements. Recovery of caloric function may serve not only as an important diagnostic sign in patients with healed perilymph fistula, even without surgical proof, but also as an expectation for the recovery of hearing loss. PMID- 7771722 TI - Hydrops-induced changes in cochlear blood flow. AB - Laser Doppler flowmetry was used to assess cochlear blood flow (CBF) in the hydropic ear in four experiments. 1) The increase in CBF elicited by local electrical stimulation of the cochlea in the hydropic ear was compared to that observed in normal controls. The magnitude of the evoked CBF change was reduced by approximately 30% in the hydropic ear compared to the normal ear. 2) The reduction in CBF evoked by direct electrical stimulation of the superior cervical ganglion was reduced by approximately one third in the hydropic ear compared to a normal ear. 3) Rhythmic (flux motion or vasomotion) variations in CBF, observed in association with lower blood pressure and thought to extend the autoregulatory range in an organ system, were reduced or eliminated in the hydropic ear. 4) The autoregulatory response to a decreased perfusion pressure, produced by decreased cardiac output, was clearly reduced relative to control in the hydropic ear. These findings represent the first report of significant CBF changes with hydrops. They are consistent with reports of increased sensitivity of the hydropic ear to trauma and stress and may be relevant considerations in the treatment of hydrops in humans. PMID- 7771724 TI - Hypoglossal schwannoma. PMID- 7771725 TI - Maxillary carcinoma arising in a postoperative sinus. PMID- 7771726 TI - Teratomas of the head and neck with emphasis on malignancy. AB - The great majority of teratomas of the head and neck present in the neonate or infant and are biologically benign and yet with a high mortality because of their space-occupying and obstructive character. Teratomas in the adult neck and sinonasal tract are histologically and biologically malignant, with an often unpredictable response to therapy. PMID- 7771727 TI - Value of radiography in the management of possible fishbone ingestion. PMID- 7771728 TI - [Study of hair in type I tricho-rhino-phalangeal syndrome]. AB - Trichorhinophalangeal syndrome has three characteristic signs: slow-growing hair, pearshaped nose with high philtrum and bradyphalangia with wedge-shaped epiphyses. We report two familial cases of type I trichorhinophalangeal syndrome. Our aim was to better identify the hair anomalies. A 22-year-old boy and his 65 year-old mother had thin sparse hair with recessed fronto-temporo-occipital hair lines. The trichogramme of the occipital region showed 52% dystrophic roots and 48% telogenic roots. Polarized light revealed monochromal hair with clear << finger-end >> rhexis. Electron scan microscopy showed thin, oval, flat or cannulated hairs and folded cuticle cells. A transverse zone in the prerhexis area had no cuticle cells and << finger-end >> fractures. Histological examination showed a normal follicle count. Sebaceous and sudoriparous glands were normal. Other characteristics of trichorhinophalangeal syndrome (facial deformity with pear-shaped nose with high philtrum, clinobrachydactylia of the fingers and toes, and radiologically wedge-shaped epiphyses) were also noted. Caryotypes were normal. We emphasize the importance of folded cuticle cells and clear rhexis leading to << finger-end >> fractures. These anomalies could serve as markers in cases with few suggestive signs. PMID- 7771729 TI - [Pemphigoid in children]. AB - INTRODUCTION: Bullous pemphigoid is rare during the childhood. The authors report the 51st case. CASE REPORT: Jeremie, a seven-month-old baby, had atypical bullous lesions. Histological examination, direct and indirect immunofluorescence were in favor of bullous pemphigoid. COMMENTS: Clinical and biological features of bullous pemphigoid are similar in the adult and in the infant. First treatment is represented by corticosteroids. Evolution is generally very good. PMID- 7771730 TI - [Facial granuloma]. AB - INTRODUCTION: The aim of this case report is to show the results of therapeutical procedures in the facial granuloma. CASE: A 48 year old male patient had multiple facial granulomas persisting for at least 8 years. They were unresponsive to dapsone. The surgical removal of two lesions and the liquid nitrogen cryotherapy of the remaining lesions were efficient without recurrence in a follow-up time of 6 months. COMMENTS: Lesions of facial granuloma do not spontaneously regress; they are easily recognized and differentiated from other conditions occurring on the face. New therapeutical approaches are welcome, even if they are empirical, in so far as they are efficient and reproducible. PMID- 7771732 TI - [Pachydermodactyly]. AB - INTRODUCTION: Histologically pachydermodactyly results from fibromatosis. Characteristically, the clinical picture occurs almost exclusively in young men. The lesion is localized on the laterodorsal aspect of the proximal phalanges of both hands. CASE REPORT: We observed a 19-year-old man with deformity of the laterodorsal aspect of the first phalanx of the fingers on both hands which had been present for several years. The clinical course and histology of the deformity as well as the lack of any bone lesions led to the diagnosis of pachydermodactyly. COMMENTS: Pachydermodactyl is a rare disease. Our case was comparable to those reported in the literature. A mechanical cause is accepted by most authors. PMID- 7771731 TI - [Pustular vasculitis disclosing Behcet disease]. AB - INTRODUCTION: Pustular vasculitis is a classical manifestation of Behcet's disease. We report a case where the papulopustular eruption formed an arch on the skin and the histology examination showed predominant lymphocytic infiltration. CASE REPORT: A 29 year-old with a past history of recurrent buccal aphthosis had developed episodic papulopustular eruptions over the past 3 years. The diagnostic of Behcet's disease was made on the basis of an association with lymphocytic meningis, uveitis and erythema nodosum. General corticosteroid therapy was effective, but did not prevent skin relapse, controlled with colchicine. DISCUSSION: Pustular vasculitis usually presents with pustular eruptions on purpuric lesions and polynuclear infiltration of the dermis. Predominant lymphocytic infiltration is usually due to a pathergy phenomenon and would be specific for Behcet's disease. In our patient, colchicine was effective, although the mechanism remains to be explained. PMID- 7771733 TI - [Acquired zinc deficiency in a breast-fed premature infant]. AB - Acquired zinc deficiency in exclusively breast-fed premature babies is a recently described entity which surprisingly, has not been reported more frequently. Its pathogenesis would appear to be the result of various factors, prematurity, exclusive breast-feeding and a suspected maternal defect, acquired or inherited, for the transfer of zinc from the blood to the breast milk. We report the case of a girl who was born at 31 weeks, exclusively breast-fed for 28 weeks and who presented a characteristic clinical feature of zinc deficiency. The mother's zinc level in the breast-milk was abnormally low. After zinc therapy and progressive weaning, the lesions dramatically improved in few days. There was no recurrence of the lesions one year after the treatment was completely stopped. With regard to this characteristic case, we outline the many pathophysiological mechanisms involved in acquired zinc deficiency. Recognition of this clinical feature by dermatologists seems essential because the required treatment is spectacularly effective and definitive. Finally, we also examine possible forms with few symptoms and we wonder if serum zinc levels should be checked in at-risk babies. PMID- 7771734 TI - [Role of sun exposure on benign melanocytic nevi. A first study in populations controlled for age, sex and phenotype]. AB - BACKGROUND: These studies were designed to assess the influence of sun exposure on nevi in white people. In order to eliminate the confounding effect of age, sex and phenotype, two parallel studies were conducted in people of the same age (17 to 24 years), sex (males) and phenotype: one in people with "red" phenotype and one in people with "dark" phenotype. RESULTS: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never exposed skin show that number of nevi is higher in sun exposed areas. In both groups the density of large and atypical nevi was maximal on intermittently sun exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently-exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life. CONCLUSIONS: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in "red" phenotype than in "dark" one, has an influence on the number of large nevi and is therefore likely to make small nevi grow. PMID- 7771735 TI - [A case for diagnosis: lepromatous leprosy]. PMID- 7771736 TI - [Cutaneous cysts and pseudocysts. II]. PMID- 7771737 TI - [T lymphocytes in the pathogenesis of chronic inflammatory skin diseases]. PMID- 7771738 TI - [Smell in dermatology]. PMID- 7771740 TI - [Can NSAID be prescribed in psoriasis?]. PMID- 7771739 TI - [Neural crest derived structures. Works on embryonal chimera and their application to neurocristopathies]. PMID- 7771741 TI - [New face lifts: preface]. PMID- 7771742 TI - [New face lifts: foreward]. PMID- 7771743 TI - [New face lifts: introduction]. PMID- 7771744 TI - [Anatomy of the superficial parts of the face and neck]. AB - The author presents four chapters concerning classical anatomy, an anatomical contribution to new facelifts, aesthetic anatomy, which recalls the aesthetic relations of the face, and finally a brief review of the mode of ageing of the face. The embryology of the superficial plane of the face and neck shows that the development of muscles of facial expression, deep and superficial fatty tissues, the facial nerve and the parotid is the result of divergent migratory movements and confluences. The anatomy is discussed in two parts: the first concerns conventional anatomy, and reviews the anatomical data acquired to date, the second proposes anatomical conclusions adapted to new surgical techniques of rejuvenation. The branches of the facial nerve are unusual in terms of their great variability. However, by using anatomical landmarks, it is possible to localize them precisely. The blood supply of the superficial tissues of the face and neck has been the subject of many studies. Deep monoblock facelifts, by sparing the blood supply of certain anatomical planes, allow the perfectly safe creation of extensive skin flaps. Some muscles of the face and neck are useful surgically. The orbicularis oculi muscle is also a muscle of the orbital margins by its depressing action on the eyebrows and levator action on the superficial malar adipose tissue. The corrugator muscle is a central element of new frontal endoscopy techniques. Elevation of the eyebrows is then ensured by the occipitofrontal complex which occupies only the medial two-thirds of the eyebrows. The zygomaticus major muscle must be released over its entire length because excessive traction on a SMAS flap can induce a disorder of facial expression. The platysma muscle plays an increasingly important role in cervical surgery and constitutes the deep guarantee of the cervical corset. The four fixed osteocutaneous points of the face: zygomatic (Mac Gregor), mandibular (Furnas), orbital (Psillakis) and masseteric play an antigravitational and functional role in facial expression. A macroscopic anatomical and histological study, performed on 60 dissections of hemifaces with several preparations defined the anatomy of the superficial musculoaponeurotic system (SMAS), jugomalar adipose planes and the nasolabial fold. The SMAS is a strictly superficial surgical anatomy structure derived from the primitive platysma muscle, and does not possess any bony insertion. It is composed exclusively of platysma and risorius muscles. There is no parotid aponeurosis. The parotid is surrounded by a capsule. Its is limited in depth by the superficial cervical aponeurosis which lines the styloid curtain (Jost, Levet).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7771745 TI - [Subperiosteal face lift or "mask-lift"]. AB - The subperiosteal facelift is, as its name indicates, a deep technique essentially adapted to the upper two-thirds of the face. It is performed via a bicoronal incision, often associated with a vestibular incision, which allows frontal, maxillary, malar, zygomatic and orbital dissection. Section of the superficial leaflet of the temporal aponeurosis reveals the DMAS (Deep Musculo Aponeurotic System) which can be used to raise all of the soft tissues of the face while protecting the frontal branch of the facial nerve. Elevation of the tissues of the face is essentially vertical and acts on the forehead, temporal region, gaze and cheekbones. Current incisions allow maximal preservation of hair and avoid ascension of the sideburns. This technique is particularly indicated in relatively young subjects. PMID- 7771746 TI - [Frontal face lift. Temporal face lift. Extraperiosteal face lift]. AB - The author describes the anatomical structures and various incisions responsible for progress in frontal facelift. He describes the technique currently adopted by the majority of authors to perform this operation. The incision has been the site of the greatest progress and the use of myoplasties remains a controversial issue. Possible combinations with blepharoplasty and with procedures used to complete the facelift at various levels are discussed. These procedures may consist of bone remodelling performed in combination with the operation or osteotomies to modify bony contours, or the use of various filling materials with their respective advantages and disadvantages. The author then describes a temporal facelift technique, which has fallen out of use, under the name of "mannequin facelift" and which, as a result of a better understanding of the planes of dissection has a renewed value in certain indications. It is an incision rather than a technique, but it should also be used with the development of endoscopy. The extraperiostal masklift is a technique which treats the middle part of the face. Its extraperiostal approach, in contrast with the subperiosteal masklift, can be used to release soft tissues and to act more precisely than by raising the periosteum which is considered to be inextensible. Its rejuvenating effect is dramatic, but it does not allow the bony appositions which can be performed via a subperiosteal approach. This technique is very well defined and allows easy progression to a complementary cervicofacial facelift. PMID- 7771747 TI - [Face lifts of the malar, jugal and nasolabial area]. AB - The author describes the various techniques, now classical, allowing correction of ageing of the middle third of the face: subcutaneous facelift, retightening of the deep planes, SMAS, platysma, as well as more recent procedures: deep facelift, composite facelift, facelift of the Superficial Adipo Cutaneous System (SACS). These techniques are designed to restore a normal position to tissues which have migrated with time: skin, fat and fibromuscular planes. The most difficult correction is that of the nasolabial pouch. PMID- 7771748 TI - [Cervical face lift]. AB - In the context of cervical facelift, classical techniques, constituting the basis for current techniques or still in use, are described in terms of the incisions, detachments and treatment of the deep adipose, muscular and glandular planes. The author then describes the technique commonly used in modern cervical restructuration before describing the possible complications and defects. PMID- 7771749 TI - [Contribution of videoendoscopy to the surgery of face rejuvenation]. AB - After a delay of several years, endoscopic surgery was introduced into cosmetic surgery of the face in 1992. Initially, its indications were very limited as they only concerned resection of corrugator muscles for the treatment of wrinkles between the eyebrows. Today, it has a new lease of life, with the ambition of replacing classical forehead facelift, by constituting a surgical approach. It replaces the bicoronal incision by means of 5 small incisions which allow detachment and resection of the depressor supercilii muscles similar to that obtained via a bicoronal incision. The skin or scalp excess is absorbed by various techniques. However, endoscopy now has other ambitions: functional fronto orbital surgery. It tries to achieve a new muscular equilibrium by resection of the depressor supercilii muscles and release of the levators: occipitofrontal muscle. In this way, this new technique achieves an entirely natural repositioning of the eyebrow. The authors describe all of the technical possibilities by endoscopy, median frontal endoscopy, endoscopic frontal facelift, endoscopic extraperiosteal masklift and endoscopic subperiosteal masklift, in the case of the forehead. A special technique has been developed: temporomalar facelift. Lastly, although cervicofacial dissection is technically possible using videoendoscopy, there nevertheless remains a major stumbling block: the excess skin. Based on an experience of more than a hundred cases over a period of more than 18 months, this technique provides extremely encouraging results leading the authors to adopt this technique definitively. PMID- 7771750 TI - [Intestinal perforations in percutaneous surgery of the kidney]. AB - Using 9 personal surveys and 11 cases found in the literature, the authors analyse the etiologies of this iatrogenic accident, the often secondary modalities of the diagnosis and the benign nature of the fistula which usually heals spontaneously. PMID- 7771751 TI - [Uretero-intestinal fistulas]. AB - Reporting their experience of these seldom described fistulas, the authors specify their etiological modalities, mainly the infected stones, the multiple clinical symptomatology and specify the various locations between the ureter and the enteral duct from the duodenum to the anal channel at any point. PMID- 7771752 TI - [Vesico-intestinal fistulas]. AB - The authors report the various locations (ileal, appendicular, colic, rectal and through Meckel diverticulum) of the fistulas between the bladder and the digestive tract and specify the mainly inflammatory etiologies and specifically those due to the Crohn disease or those caused by tumors aggravated by irradiation and repeated surgery. PMID- 7771753 TI - [Vesico-sigmoidal fistulas of diverticular origin]. AB - From 1984 to 1993, 11 patients (7 men and 4 women, mean aged 70 years) underwent surgical procedure for sigmoido-vesical fistula due to diverticulitis. Fecaluria and/or pneumaturia was present in 10 patients. The diagnosis of sigmoido-vesical fistula due to diverticulitis was confirmed by urologic and colonic investigations. All patients underwent surgical treatment. One patient underwent creation of a diverting colostomy alone because of a poor general status. Definitive surgical correction of the fistula with resection of the diverticular colon was attempted in the remaining 10 patients, including colo-rectal anastomosis. A temporary diverting colostomy was performed in 5 cases. There was no post operative death. One small wound infection occurred. All the diverting colostomies have been closed, meanly 2 months after the operation. Concerning long-term results, 3 patients died from an independant reason. All the other patients are alive and asymptomatic from the urologic as well as the digestive point of view. Based on these results, we advocate single stage repair, including correction of the fistula and resection of the diverticular colon with colo rectal anastomosis, in cases of good local and general conditions. PMID- 7771754 TI - [Prostatic or urethral rectal fistulas]. AB - Reporting 7 new observations of prostatic or urethro-rectal fistulas, the authors insist on their etiological modalities specially of traumatical, inflammatory, post-irradiation, cancerous and congenital origin. The diagnosis methods and surgical techniques are also mentioned. PMID- 7771755 TI - [Congenital uro-intestinal fistulas]. AB - The congenital uro-enteral fistula are observed essentially in boy and quite exclusively with anorectal malformation. Cloacal anomaly in girl and cloacal exstrophy in both sexes are so exceptional than complex malformations. PMID- 7771756 TI - [Uro-intestinal fistulas of cancerous origin]. AB - Malignant entero-vesical fistulas are uncommon. Colonic malignancy is the main cause although fistula are present in just 1%. Pneumaturia and fecaluria are pathognomonic for entero-vesico-fistula and are present in half of cases. By combining the results of cystoscopy, barium enema and urine culture, fistula can be identified in almost all the cases. Escherichia coli, Streptococcus faecalis and Proteus mirabilis are very often isolated from the urine cultures. The management of entero-vesical-fistula depends of the etiology. The treatment requires in most of the case resection of the diseased bowel with partial cystectomy and primary anastomosis. But sometimes, is necessary to perform a diverting colostomy and urinary diversion. PMID- 7771757 TI - [News from the 23rd International Congress of Urology. Sydney, 18-22 September 1994]. PMID- 7771758 TI - [Uro-intestinal fistulas]. PMID- 7771759 TI - [Intestinal urinary fistulas of renal and pelvis origin]. AB - As the authors point out the uncommon occurrence of these fistulas between the calicopyelic cavities with the colon, the duodenum and still more unusually with the stomach and the jejunum, they report the etiological and clinical features found in the published cases. Usually the only solution is a nephrectomy. PMID- 7771760 TI - The 8th International Conference on Antiviral Research. Santa Fe, New Mexico, April 23-28, 1995. Abstracts. PMID- 7771761 TI - Protein splicing--the lengths some proteins will go to. AB - We review the recently discovered phenomenon of protein splicing which is the excision of an internal protein sequence at the protein level rather than at the RNA level. The means by which examples of protein splicing have been identified are described, and the similarities of the internally spliced protein products (or inteins) are discussed. Comparisons are made between inteins and group I RNA introns. We describe the evidence supporting excision of intiens by a post translational autocatalytic reaction of a full length polypeptide precursor, rather than by RNA splicing. An examination is made of some of the proposed mechanism schemes and the supporting them presented. PMID- 7771763 TI - Ballistosporous yeasts found on the surface of plant materials collected in New Zealand. 1. Six new species in the genus Sporobolomyces. AB - Six new species of ballistosporous yeast, the genus Sporobolomyces, were isolated from dead leaves and fruit of plants collected in New Zealand; Sp. novazealandicus, Sp. dimmenae, Sp. coprosmicola, Sp. coprosmae, Sp. dracophyllus, and Sp. taupoensis. These species differ from any hitherto known species of Sporobolomyces based on chemotaxonomic characteristics. PMID- 7771762 TI - Evaluation of image analysis and laser granulometry for microbial cell sizing. AB - A direct cell size measurement technique and an image analysis based sizing method were developed. The former consisted of a manual size measurement of the two-dimensional cell images on a video screen, with automatic data recording. This method was chosen as the reference. The latter, a semiautomatic method took advantage of a commercial computer program designed for image processing and particle morphology analysis. It gave average and median size values which were compatible with the manual method. However, the performance of these time consuming methods is limited. Hence, the laser granulometry technique, intrinsically far more powerful while capable of analysing millions of sample objects in a short time delay, was applied. The comparison revealed that this method gives too low size values, particularly in disagreement with the known dimensions of the bacterial (Zymomonas mobilis) cells. A size correction method was developed to realign the granulometry results of Z mobilis cell samples with those of the direct manual measurement method. PMID- 7771764 TI - Confirmation of the nomenclatural status of Malassezia pachydermatis. AB - Malassezia strains from dogs and rhinoceros all proved identical using mole% G+C and nDNA/DNA reassociation experiments. The use of the name Malassezia pachydermatis, originally described for a strain isolated from a rhinoceros, is thus justified for non lipid-dependent strains of other sources. PMID- 7771765 TI - Babjevia gen. nov.--a new genus of the Lipomycetaceae. AB - The species described as Lipomyces anomalus Babjeva & Gorin shows significant genetic and phenotypic divergence from the type species Lipomyces starkeyi Lodder & Kreger-van Rij in terms of rRNA base sequence substitution and ascosporal and septal ultrastructure. The species is consequently reclassified in the new, unispecific genus Babjevia, as Babjevia anomala. PMID- 7771767 TI - Cloning of genes required for hypersensitivity and pathogenicity in Pseudomonas syringae pv. aptata. AB - A genomic library of Pseudomonas syringae pv. aptata strain NCPPB 2664, which causes bacterial blight of sugar beet, lettuce and other plants, was constructed in the cosmid vector pCPP31. The 13.4 kb EcoRI fragment of the cosmid pHIR11, containing the hrp (hypersensitive response and pathogenicity) gene cluster of the closely related bacterium Pseudomonas syringae pv. syringae strain 61, was used as a probe to identify a homologous hrp gene cluster in P. syringae pv. aptata. Thirty of 2500 cosmid clones, screened by colony hybridization, gave a strong hybridization signal with the probe, but none of these conferred to the non-pathogenic bacterium, Pseudomonas fluorescens, the ability to elicit the hypersensitive response (HR) in tobacco. Southern blot analysis of EcoRI-digested genomic DNA of P. syringae pv. aptata showed hybridizing bands of 12 kb and 4.4 kb. Only a 12 kb fragment hybridized in digests of the cosmids. Cosmid clone pCPP1069 was mutagenized with Tn10-minitet and marker-exchanged into the genome of P. syringae pv. aptata. Three resulting prototrophic mutant strains failed to elicit the HR in tobacco and to cause disease in lettuce. The DNA flanking the Tn10-minitet insertions from mutated derivatives of pCPP1069 hybridized with the 10.6 kb Bg/II fragment of pHIR11. These results indicate that P. syringae pv. aptata harbours hrp genes that are similar to, but arranged differently from, homologous hrp genes of P. syringae pv. syringae. PMID- 7771768 TI - Properties of enzymes involved in D-galactonate catabolism in fungi. AB - Two enzymes catalyze the two step reactions in the D-galactonate nonphosphorolytic catabolic pathway of Aspergillus terreus, namely D-galactonate dehydratase and 2-keto-3-deoxy-D-galactonate (KDGal) aldolase. Maximum enzyme activities were obtained at 40 degrees C and pH 8.0 or at 50 degrees C and pH 7.5 for these two enzymes, respectively. Stability of the two enzymes under different conditions was investigated. From a Lineweaver-Burk plot of the reciprocal of initial velocities and substrate concentrations, apparent Km values were calculated for D-galactonate, pyruvate and glyceraldehyde and found to be 8.33, 14.28 and 5.55 mM, respectively, in crude cell-free extracts. Results indicated the requirement of magnesium cation for D-galactonate dehydratase activity at an initial concentrations of 10(-2) M. The presence of Mg2+ in the reaction mixture seems to induce greatly the fitness of the dehydratase with D-galactonate as no activity could be detected with 24-h dialyzed extract in the absence of magnesium cation. PMID- 7771769 TI - Partial conversion of cinnamic acid into styrene by growing cultures and cell free extracts of the yeast Cryptococcus elinovii. AB - Cultures of Cryptococcus elinovii CBS 7051 grown at the expense of cinnamic acid as the sole source of carbon and energy partially converted this substrate into styrene. The latter is toxic and eventually kills the culture. Cell-free extracts of cultures grown on cinnamic acid produced styrene from cinnamate. Other basidiomycetous yeasts tested did not produce styrene from cinnamic acid. PMID- 7771766 TI - Genes for beta-lactam antibiotic biosynthesis. AB - The genes pcbAB, pcbC and penDE encoding enzymes involved in the biosynthesis of penicillin have been cloned from Penicillium chrysogenum and Aspergillus nidulans. They are clustered in chromosome I (10.4 Mb) of P. chrysogenum, but they are located in chromosome II of Penicillium notatum (9.6 Mb) and in chromosome VI (3.0 Mb) of A. nidulans. Expression studies have shown that each gene is expressed as a single transcript from separate promoters. Enzyme regulation studies and gene expression analysis have provided useful information to understand the control of gene expression leading to overexpression of the genes involved in penicillin biosynthesis. Cephalosporin genes have been studied in Cephalosporium acremonium and also in cephalosporin-producing bacteria. In C. acremonium the genes involved in cephalosporin biosynthesis are separated in at least two clusters. Cluster I (pcbAB-pcbC) encodes the first two enzymes of the cephalosporin pathway which are very similar to those involved in penicillin biosynthesis. Cluster II (cefEF-cefG), encodes the last three enzymatic activities of the cephalosporin pathway. It is unknown, at this time, if the cefD gene encoding isopenicillin epimerase is linked to any of the two clusters. In cephamycin producing bacteria the genes encoding the entire biosynthetic pathway are located in a single cluster extending for about 30 kb in Nocardia lactamdurans, and in Streptomyces clavuligerus. The cephamycin clusters of N. lactamdurans and S. clavuligerus include a gene lat which encodes lysine-6 aminotransferase an enzyme involved in formation of the precursor alpha aminoadipic acid. The N. lactamdurans cephamycin cluster includes, in addition, a beta-lactamase (bla) gene, a penicillin binding protein (pbp), and a transmembrane protein gene (cmcT) that is probably involved in secretion of the cephamycin. Little is known however about the mechanism of control of gene expression in the different beta-lactam producers. The availability of most of the structural genes provides a good basis for further studies on gene expression. This knowledge should lead in the next decade to a rational design of strain improvement procedures. The origin and evolution of beta-lactam genes is intriguing since their nucleotide sequences are extremely conserved despite their restricted distribution in the microbial world. PMID- 7771770 TI - Purification and properties of oxaloacetate decarboxylase from Corynebacterium glutamicum. AB - Oxaloacetate (OAA) decarboxylase (E.C. 4.1.1.3) was isolated from Corynebacterium glutamicum. In five steps the enzyme was purified 300-fold to apparent homogeneity. The molecular mass estimated by gel filtration was 118 +/- 6 kDa. SDS-PAGE showed a single subunit of 31.7 KDa, indicating an alpha 4 subunit structure for the native enzyme. The enzyme catalyzed the decarboxylation of OAA to pyruvate and CO2, but no other alpha-ketoacids were used as substrate. The cation Mn2+ was required for full activity, but could be substituted by Mg2+, CO2+, Ni2+ and Ca2+. Monovalent ions like Na+, K+ or NH4+ were not required for activity. The enzyme was inhibited by Cu2+, Zn2+, ADP, coenzyme A and succinate. Avidin did not inhibit the enzyme activity, indicating that biotin is not involved in decarboxylation of OAA. Analysis of the kinetic properties revealed a Km for OAA of 2.1 mM and a Km of 1.2 mM for Mn2+. The Vmax was 158 mumol of OAA converted per min per mg of protein, which corresponds to an apparent kcat of 311 s-1. PMID- 7771771 TI - Protein sulfhydryls and their role in the antioxidant function of protein S thiolation. AB - Protein S-thiolation/dethiolation, i.e., the oxidation of protein sulfhydryls to mixed disulfides and their reduction back to sulfhydryls, is an early cellular response to oxidative stress (1-5). This response may be elicited by oxidative phenomena of diverse origins, and the few cases that have been studied extensively give a limited insight into the metabolic roles and the molecular mechanism of the process. Much of our current understanding arose from experiences with isolated proteins containing "reactive" sulfhydryls (6, 7), but recent experiments at the cellular level have begun to reveal interesting insights that suggest a complexity and importance not appreciated previously (8). This article will discuss the current status of experiments that relate to both the role of the cellular process and to the reactivity of selected proteins that participate in the cellular processes. The discussion will center on the role of glutathione, a molecule of central interest in every aspect of protein S thiolation and dethiolation. PMID- 7771772 TI - Dihydroxy-acid dehydratase, a [4Fe-4S] cluster-containing enzyme in Escherichia coli: effects of intracellular superoxide dismutase on its inactivation by oxidant stress. AB - Dihydroxy-acid dehydratase (DHAD) has a [4Fe-4S] cluster and is reported to be facilely inactivated by oxidant stress. To directly assess the biological effects in vivo of superoxide dismutase (SOD) on the oxidant sensitivity of DHAD, we used an Escherichia coli K-12 parent strain (CGSC5073) and derived strains OB 1, OB 2, and OB 3 that lacked one of or both FeSOD and MnSOD. In the K-12 parent strain half the cellular DHAD activity was lost in 15 min at 0.8 atm oxygen, less than 10 microM aerobic nitrofurantoin, or about 5 microM aerobic paraquat (PQ) and in about 1 min at 10 microM aerobic PQ. Oxygen and metabolism were required for PQ to inactivate DHAD in cells; adding dithiothreitol to cell-free extracts did not restore DHAD activity. The Km was not appreciably changed for DHAD that was 50 and 70% inactivated in cells, respectively, by hyperbaric oxygen (HBO) and PQ, compared to cells in exponential, aerobic growth. Thus, active site oxidative impairment of individual enzyme molecules apparently was all-or-none. DHAD activity was greatly decreased when measured in extracts made from strains that lacked both SODs unless SOD was added to cell suspensions before extracts were made. DHAD was more sensitive in strains lacking both SODs than in the parent strain to inactivation by aerobic PQ and HBO. Anaerobic (compared to aerobic) growth increased DHAD specific activity by 20% or less in the parent strain and in strains OB 1 and OB 2 (lacking MnSOD and FeSOD, respectively); however, in strain OB 3 (lacking both SODs) DHAD was increased 60%. DHAD was partially inactivated by the oxidant stress of aerobic growth, but remained in a form detectable by DHAD antibody, and the ratio of active to inactive DHAD decreased greatly in cells lacking SOD. Thus, SOD helped maintain DHAD as an active holoenzyme and benefitted cells growing aerobically or when exposed to low levels of PQ. PMID- 7771773 TI - Relative alpha-tocopherol deficiency in cultured cells: free radical-mediated lipid peroxidation, lipid oxidizability, and cellular polyunsaturated fatty acid content. AB - We propose that most cultured cells are deficient in vitamin E. Using our optimized assay for tocopherol, we find that L1210 lymphoblastic leukemia cells, cultured in standard growth media, contain only 2.3 +/- 0.03 micrograms of tocopherol/10(8) cells, whereas when they are transplanted and grown for the same time in the ascites fluid of mice fed standard diets, this increases to 5.8 +/- 0.6 micrograms of tocopherol/10(8) cells. This apparent tocopherol deficiency in cultured cells is likely due to the low concentrations of tocopherol contained in most tissue culture media, even with the addition of serum. To further study this apparent deficiency and the relationship of cellular tocopherol to membrane lipid bis-allylic hydrogen positions, we supplemented the growth media of L1210 lymphoblastic leukemia cells with alpha-tocopherol and compared the resultant cellular tocopherol content to the degree of unsaturation of cellular lipids, alpha-Tocopherol was incorporated by cells in a time- and concentration-dependent manner with plateaus at 24 h and 100 microM, respectively. A maximum 400% increase in cellular tocopherol was easily achieved. By experimentally modifying the fatty acid content of cellular lipids, we were able to determine that cellular tocopherol uptake and content is not a function of cellular lipid composition; cells enriched with polyunsaturated lipids incorporated tocopherol to the same extent as those enriched with more saturated lipids. Thus, as the cellular polyunsaturated fatty acid content increases, the tocopherol:bis-allylic position ratio in the cells decreases, resulting in less antioxidant protection for each lipid double bond. Consequently, when polyunsaturated fatty acid enriched cells are exposed to an oxidative stress, such as Fe2+, their tocopherol levels decline much faster than cells enriched with saturated fatty acids. This decline is consistent with their respective tocopherol:bis-allylic position ratio. These results provide a basis, at the cellular level, for investigators to consider vitamin E when studying cell response to oxidative stress. PMID- 7771774 TI - Solution structure and function in trifluoroethanol of PP-50, an ATP-binding peptide from F1ATPase. AB - PP-50, a synthetic peptide, based on residues 141-190 of the beta-subunit of mitochondrial F1ATPase, containing the GX4GKT consensus sequence for nucleoside triphosphate binding, binds ATP tightly (Kd = 17.5 microM) as found by fluorescence titration at pH 4.0. CD and 2D proton NMR studies at pH 4.0 revealed two beta-turns, regions of extended secondary structure, transient tertiary structure, and flexibility in the GX4GKT region (W.J. Chuang, C. Abeygunawardana, P. L. Pedersen, and A. S. Mildvan, 1992, Biochemistry 31, 7915-7921). CD titration of PP-50 with trifluoroethanol (TFE) reveals a decrease in ellipticity at 208 and 222 nm, saturating at 25% TFE. Computer analysis indicates that 25% TFE increases the helix content from 5.8 to 28.6%, decreases the beta-structure from 30.2 to 20.2% and decreases the coil content from 64 to 51.2%. Fluorescence titrations of H2ATP2- with PP-50 in 25% TFE yields a Kd of 7.3 microM, 2.4-fold tighter than in H2O, probably due to TFE increasing the activity of H2ATP2- . PP 50 completely quenches the fluorescence of H2ATP2- in 25% TFE, while in H2O the fluorescence quenching is only 62%. In H2O the binding of H2ATP2- increases the structure of PP-50 as detected by CD, but in 25% TFE no significant change in CD is found on binding either H2ATP2- or Mg2+ HATP (Kd = 14 microM). The complete proton NMR spectrum of PP-50 in 25% TFE has been assigned. The solution structure, determined by distance geometry, molecular dynamics with simulated annealing, and energy minimization, consists of a coil (residues 1-8), a strand (residues 9-12), a loop (residues 13-22) containing the GX4GKT consensus sequence (residues 16-23), an alpha-helix (residues 23-36), a turn (residues 38-41), and a coil (residues 42-50), similar to that of the corresponding region of the X-ray structure of F1ATPase (J.P. Abrahams, A.G.W. Leslie, R. Lutter, and J. E. Walker, 1994 Nature 370, 621-628) and to the structure of a homologous peptide from the ATP-binding site of adenylate kinase (D. C. Fry, D. M. Byler, H. Susi, E. M. Brown, S. A. Kuby, and A. S. Mildvan, 1988 Biochemistry 27, 3588-3598), beta, gamma-Bidentate Cr3+ ATP binds to PP-50 with the Cr3+ pyrophosphate moiety approaching the epsilon-methylene group of K22 in the GX4GKT consensus sequence, in agreement with the X-ray structure of the Mg2+ AMPPNP complex of F1ATPase. PMID- 7771775 TI - Site-directed mutagenesis of the substrate binding site of porcine fructose-1,6 bisphosphatase. AB - Asn 212, Arg 243, Tyr 244, Tyr 264, and Lys 274, which are conserved in all known primary sequences of fructose-1, 6-bisphosphatase, are located in the substrate binding domain on the basis of the crystal structure of the enzyme. Mutations of the five residues of porcine liver fructose-1,6-bisphosphatase (Asn212Ala, Arg243 Met, Tyr244Phe, Tyr264Phe, and Lys274Leu) were carried out by site-directed mutagenesis. The wild-type and mutant forms of the enzyme were purified to homogeneity and characterized by initial rate kinetics and circular dichroism spectrometry. The mutants exhibited kcat values that are similar to those of the wild-type enzyme. The Km values for fructose 1,6-bisphosphate of the mutants are 6- to 44-fold higher than that of the wild-type enzyme. The Ki values for fructose 2,6-bisphosphate and AMP of the mutants increased from 56- to 1950-fold and 12- to 27-fold, respectively, relative to the wild-type enzyme. The alteration of inhibition constants for both inhibitors suggest that these five active site residues are involved in the inhibition by fructose 2,6-bisphosphate and AMP. No apparent differences in secondary structure of the wild-type and mutant forms of fructose-1,6-bisphosphatase were observed as measured by circular dichroism spectrometry. This report demonstrates that Asn 212, Arg 243, Tyr 244, Tyr 264, and Lys 274 not only are the sites for substrate binding, but also play an important role in the binding affinity of inhibitors fructose 2,6-bisphosphate and AMP. PMID- 7771776 TI - Influence of glucose on pyruvate carboxylase expression in pancreatic islets. AB - Pancreatic islets were cultured for 1 day in the presence of 1 to 20 mM glucose and islet proteins were separated on polyacrylamide gels and transferred to nitrocellulose. Pyruvate carboxylase and an unidentified biotin-containing protein were visualized with [125I]streptavidin followed by autoradiography. The amount of pyruvate carboxylase was proportional to the concentration of glucose. Estimates of the amount of the enzyme in islets were made by comparing the density of the islet pyruvate carboxylase band with a standard curve of various amounts of authentic pyruvate carboxylase. This indicated that the enzyme comprised 0.4% of total islet protein. Net synthesis of the enzyme was increased by cAMP and methyl succinate. A nuclear run-on assay showed that glucose caused increases in pyruvate carboxylase and pyruvate dehydrogenase E1 alpha subunit transcripts and decreases in branched chain ketoacid dehydrogenase E1 alpha transcripts in rat insulinoma (RINm5F) cells. Pancreatic islets cultured in the presence of 1 mM glucose for 1 day cannot respond to glucose with insulin release. Previous studies demonstrated that carbon flux into the citric acid cycle intermediates via both carboxylation and decarboxylation is decreased in glucose-incapacitated islets (M. J. MacDonald, 1993, Arch. Biochem. Biophys. 300, 205-214), 1993). The current results support the idea that carboxylation of glucose-derived pyruvate, as well as decarboxylation of pyruvate, is important for glucose-induced insulin secretion. PMID- 7771777 TI - Studies on the catalytic mechanism of pig purple acid phosphatase. AB - Several independent experiments failed to reveal any evidence in support of the involvement of a phosphoryl-enzyme intermediate in the catalytic mechanism of pig allantoic fluid purple acid phosphatase: (i) attempts to label enzyme with phosphate derived from [32P]p-nitrophenyl phosphate were unsuccessful; (ii) values of kcat for a series of phosphate derivative varied over a wide range, with the enzyme showing a marked preference for activated ester and anhydride substrates over those with a stable leaving group; (iii) burst titrations revealed a "burst" of p-nitrophenol from p-nitrophenyl phosphate only when the enzyme was added after the substrate, suggesting that this result was an artifact of the order of addition of reagents; (iv) transphosphorylation from p nitrophenyl phosphate to acceptor alcohols could not be detected, even under conditions where a transphosphorylation to hydrolysis ratio as low as 0.015 could have been measured; (v) enzyme-catalyzed exchange of 180 between phosphate and water was demonstrated, although at a rate much slower than that observed for other phosphatases where the involvement of a phosphoryl-enzyme intermediate in the mechanism has been clearly established. The present results are compared with those obtained in similar studies on other phosphatases, particularly the highly homologous beef spleen purple acid phosphatase, and their implications for the catalytic mechanism of the purple acid phosphatases are discussed. PMID- 7771778 TI - Antioxidant action of neuromelanin: the mechanism of inhibitory effect on lipid peroxidation. AB - Iron and lipid peroxidation are believed to be involved in the degeneration of pigmented neurons in Parkinson's disease. Melanin-iron interaction is thought to play a role in iron accumulation and reactivity. The purpose of this study was to examine antioxidant properties of isolated natural and synthetic neuromelanin. Effect of neuromelanin from substantia nigra and its synthetic model, dopamine melanin, on lipid peroxidation, induced by ferrous ions and free-radical initiators, has been studied in methyl linoleate aqueous dispersions. 2,2' Azobis(amidinopropane)dihydrochloride and 2,2'-azobis(2,4-dimethyl-valeronitrile) were used as water-soluble and lipid-soluble radical initiator, respectively. Rate of oxidation was followed quantitatively by measuring oxygen uptake and accumulation of lipid hydroperoxides. Melanin had a distinct protective effect on lipid peroxidation induced by ferrous ions or water-soluble free-radical initiator but was relatively inefficient when peroxidation was initiated with lipid-soluble compound. It also inhibited iron-catalyzed decomposition of methyl linoleate hydroperoxides in the presence of ascorbate. Extent of the inhibition depended on the ratio of melanin to iron. Taken together, these results provide strong support for the idea that neuromelanin of pigmented neurons can act as a natural antioxidant by sequestering redox-active metal ions. PMID- 7771779 TI - Purification, cloning, and sequencing of archaebacterial pyrophosphatase from the extreme thermoacidophile Sulfolobus acidocaldarius. AB - Cytoplasmic pyrophosphatases are indispensible for the function of cellular bioenergetics. From the extreme thermoacidophilic archaeon Sulfolobus acidocaldarius, situated at one of the lowest branches of the phylogenetic tree, a cytosolic pyrophosphatase has been isolated and purified 200-fold to electrophoretic homogeneity by combining ion-exchange and gel-exclusion chromatography. The native enzyme consists of a homotetramer of 71 kDa apparent molecular mass; the subunit displays an apparent molecular mass of 17 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has an absolute requirement for divalent cations (Mg2+) and a temperature optimum of 75 degrees C coinciding with the growth optimum of the organism; the apparent estimated activation energy is 79.5 kJ/mol. A large variety of cytosolic extracts from other archaebacteria has been probed with a polyclonal antiserum raised against the purified protein; surprisingly, except for an extremely weak signal with S. solfataricus none of the other organisms showed any cross-reactivity. Also, Escherichia coli PPase does not cross-react. Based on N-terminal sequencing the gene has been cloned and sequenced. It codes for a 173-amino-acid protein with a calculated molecular mass of 19,365 kDa. Alignment with known eucaryotic and procaryotic PPases reveals invariant conservation of all residues presently assumed to be involved in metal and substrate binding. Unexpectedly, the highest similarity is found with the enzyme from the phylogenetically extremely distant eubacterium E. coli, but immunological cross-reactivity is absent. Similarity to the only known other archaebacterial PPase is much weaker. Using the 3D structure of the Thermus thermophilus enzyme as a scaffold an energy-minimized structural model is presented, deviating only minimally from the former. The structural features are discussed. The enzyme provides an excellent model for studies of thermostability and folding dynamics since heterologous overexpression has been achieved and genetically mutated forms become accessible. PMID- 7771780 TI - CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4. AB - Human cytochrome CYP3A4 is the most abundant of all the P450s in human liver and is involved in the metabolism of many environmental toxicants and drugs. Kinetic studies with CYP3A4 have been hampered due to low activity of this enzyme obtained from recombinant gene expression systems or difficulty in reconstituting activity with the native enzyme purified from human liver. To overcome these obstacles, we have expressed high levels of catalytically active CYP3A4 and human NADPH-cytochrome P450 reductase (CYPOR) together in two insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni (T.ni), via a single recombinant baculovirus carrying both cDNAs (CYP3A4-OR). Microsomes containing recombinant CYP3A4-OR from these cell lines were up to 50-times more active in testosterone 6 beta-hydroxylase activity than recombinant CYP3A4 expressed alone and supplemented with purified rabbit CYPOR. The spectral P450 content of CYP3A4-OR T.ni microsomes was 107 pmol/mg microsomal protein and the cytochrome c reductase activity was 3904 units/mg. Recombinant CYP3A4-OR was catalytically similar to human liver CYP3A4 based on similarities in the testosterone metabolite profile, time course of metabolite formation, Vmax and Km values (for CYP3A4-OR, Vmax was 8.8 nmol/min/mg microsomal protein [70 nmol/min/nmol CYP3A4] and Km was 33 microM), the extent of inhibition by 100 microM troleandomycin (> 75%) in the presence of 25 microM testosterone, and the degree of P450 activation in the presence of 20 microM 7,8-benzoflavone. The coexpression of recombinant cytochrome b5 with CYP3A4-OR did not result in an additional increase in CYP3A4 OR activity. PMID- 7771781 TI - Generation and remodeling of phospholipid molecular species in rat hepatocytes. AB - In order to assess the relationship between de novo phospholipid synthesis and remodeling by deacylation-reacylation, we have pulse-labeled glycerolipids by incubating rat hepatocytes in media containing either [U-14C]glycerol or H218O. Further incubation for up to 2 h in the absence of the labeled substrates and analysis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) provided information on the remodeling of newly synthesized molecular species by deacylation-reacylation at the sn-1 or sn-2 positions of glycerol. We conclude that de novo synthesis of PC and PE yields primarily four molecular species: 16:0 18:2 (n-6), 16:0-18:1, 16:0-22:6 (n-3), and 18:1-18:2 (n-6). Remodeling occurs in both lipid classes by replacement of the fatty acids at the sn-1 position with stearic acid, 18:0, or at the sn-2 position with arachidonic acid, 20:4 (n-6). A major molecular species of both PC and PE, 18:0-20:4 (n-6), appears to be produced by deacylation-reacylation at both the sn-1 and sn-2 positions and not to be further remodeled. De novo synthesis and remodeling of PC and PE in rat hepatocytes occur at similar rates, involve precursor-product relationships among newly synthesized molecular species, and therefore may be regulated as a single metabolic process. PMID- 7771782 TI - Identification of a 10 S trypsin-like protease that cross-reacts with anti proteasome antibody in sea urchin egg jelly. AB - We have identified 27- and 26-kDa polypeptides in sea urchin egg jelly, both of which cross-reacted with the antibody against 20 S proteasome (multicatalytic proteinase) isolated from sea urchin sperm. Separation of egg jelly fraction by gel filtration or sucrose density gradient centrifugation revealed that these polypeptides comigrated as a complex with a molecular size much smaller than that of proteasome: the apparent molecular mass and the sedimentation coefficient were 200 kDa and 10 S, respectively. This protease significantly hydrolyzed the fluorogenic synthetic substrates for trypsin-like protease but little hydrolyzed those for chymotrypsin-like protease. Trypsin-like activity of sperm proteasome was activated up to more than threefold by a low concentration of sodium dodecyl sulfate (SDS), whereas the egg jelly 10 S protease was inhibited by SDS. Two dimensional immunoblot and peptide mapping revealed that the 26-kDa polypeptide is a degradative product of 27-kDa polypeptide and that the 10 S protease is composed of a proteasome-related single 27-kDa polypeptide and its modified forms. These results indicate the presence of a 10 S novel assembly of a proteasome subunit only with trypsin-like activity. PMID- 7771783 TI - Cyanide inhibition of porcine kidney diamine oxidase and bovine plasma amine oxidase: evidence for multiple interaction sites. AB - The interactions of cyanide and phenylhydrazine with porcine kidney diamine oxidase (PKDAO) and bovine plasma amine oxidase (BPAO) (EC 1.4.3.6) have been investigated. Cyanide displays mixed noncompetitive inhibition against amine substrates and also against O2. EPR spectroscopy shows that cyanide binds to an equatorial site on Cu(II) and can be displaced by chloride, which is not an inhibitor, without recovery of activity, indicating that Cu(II)-bound cyanide is not inhibitory. 14CN-. studies have shown that one cyanide in PKDAO and two in BPAO are covalently and irreversibly bound per enzyme dimer at an unknown site, even under conditions where cyanide is not bound to Cu(II). These cyanides have no effect on activity or on binding of phenylhydrazine to the enzymes. Cyanide also binds reversibly to the organic cofactor in both enzymes, presumably as a cyanohydrin, leading to the observed mixed noncompetitive inhibition against substrate. In both enzymes, two phenylhydrazines react per enzyme dimer. The kinetics of phenylhydrazine titration are affected by cyanide, which indicates that phenylhydrazine and cyanide react at the same carbonyl group in the enzymes. The results suggest that inhibition of amine oxidases by cyanide is through a carbonyl reagent and a Cu(I) ligand rather than through a Cu(II) ligand. PMID- 7771784 TI - The ESR properties, DNA nicking, and DNA association of aged solutions of catechol versus aqueous extracts of tar from cigarette smoke. AB - Previous studies in our laboratories have shown that extracts from mainstream or sidestream tobacco smoke nick DNA. These solutions contain the tar semiquinone free radical, and the tar radical becomes associated with cellular DNA. Aged solutions of catechol contain a semiquinone species that has ESR properties similar to those of the radical in cigarette tar extracts, and we have used these catechol solutions as a model for the tar radical. Both the radical in aged catechol solutions and the cigarette tar radical become associated with the DNA in mammalian cells and also nick DNA. The nicking of DNA caused by both tar and aged catechol solutions follows saturation kinetics. Aged catechol solutions thus allow the study of a model for the radical present in cigarette tar, without interference from the other toxic constituents in tar extracts. PMID- 7771785 TI - Kinetic, binding, and NMR studies of perdeuterated yeast phosphoglycerate kinase and its interactions with substrates. AB - Perdeuterated yeast phosphoglycerate kinase (2HPGK) was prepared from yeast cells grown in 99.9% 2H2O and an acid hydrolysate from deuterated algal cells. Kinetic and binding studies suggested that perdeuterated enzyme was similar to the isotopically normal PGK. The use of 2HPGK not only eliminated the spectral overlap between the enzyme and substrate nuclear Overhauser effect (NOE) cross peaks, but also permitted observation of weak transfer NOE cross-peaks between the substrate protons that are greater than 4 A apart. Intensity of NOE cross peaks was used to determine the interproton distances of enzyme-bound Mg(II)dATP. These distances were then used in model building studies to determine the conformation of Mg(II)dATP. The average conformation of enzyme-bound dATP is anti with O4'/C2' endo ribose pucker and trans, gauche about the C4'-C5' bond. Although many spin diffusion pathways were eliminated by protein deuteration, spin diffusion was still observed between the protons of the substrate at mixing times longer than 25 ms. PMID- 7771786 TI - Casein zymography: a method to study mu-calpain, m-calpain, and their inhibitory agents. AB - A zymographic assay for calpains in nondenaturing casein-containing polyacrylamide gels was developed. Calpain samples were run into the polyacrylamide gels by electrophoresis using a Tris-glycine buffer containing 1 mM EGTA to stabilize calpains. Upon completion of the electrophoresis, the gels were washed and incubated in a calpain activation buffer containing 1-4 mM calcium and 10 mM dithiothreitol for 20-24 h. After staining of the casein gels with Coomassie blue G250, both mu-calpain and m-calpain showed up as clearing bands. The amount of calpain loaded was proportional to the brightness of the clearing band. m-calpain can be easily distinguished from mu-calpain due to its higher mobility in the gel. Irreversible inhibitor (e.g., E64c) or tight-binding calmidazolium-treated mu-calpain remained inactive in the casein zymogram, whereas reversible inhibitor (e.g., calpain inhibitor I) was released from the protease by migration and dilution, lifting its inhibition. Crude homogenate of cultured cells (erythrocytes, Molt-4 and cerebrocortical neurons) or tissue (rat brain) can be directly analyzed for the presence of calpain isoforms despite the presence of endogenous calpastatin. Using this technique, mu-calpain activity in Molt-4 cells was found to decrease progressively with A23187 treatment, as a reflection of autolytic inactivation. PMID- 7771787 TI - Identification of two binding proteins for halogenated aromatic hydrocarbons in the hard-shell clam, Mercenaria mercenaria. AB - Earlier studies have reported an unusually high incidence of gonadal tumors in marine bivalves in areas of potentially high exposure to herbicides including 2,4 dichlorophenoxyacetic acid and 2,4,5-trichlorophe-noxyacetic acid. Some herbicides can be contaminated by halogenated aromatic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Most of the effects of planar halogenated aromatic compounds, including carcinogenic effects in vertebrates, appear to be mediated through binding to the aryl hydrocarbon receptor. The current study investigated whether halogenated aromatic hydrocarbon-binding proteins are present in the marine bivalve, Mercenaria mercenaria. We used the TCDD photoaffinity analog 2-azido-3-[125I]-iodo-7, 8-dibromodibenzo-p-dioxin to detect the presence of two proteins (28 and 39 kDa) in cytosols prepared from M. mercenaria that specifically bound this ligand. Expression of these proteins is tissue-dependent with the highest concentrations being observed in gill and gonadal tissue. Gonadal tissue also exhibited gender-specific expression with female clams exhibiting higher levels of the 39-kDa protein. Gender-and tissue specific expression are consistent with the hypothesis that these proteins might be involved in the carcinogenic response observed in clams exposed to herbicides. PMID- 7771788 TI - Inhibition of rat liver mitochondrial permeability transition by respiratory substrates. AB - The mitochondrial inner membrane can undergo a permeability increase known as "permeability transition" elicited by Ca2+ and several other inducing agents. In general, the condition of oxidative stress acts as an inducer, at variance with antioxidants and reducing agents that inhibit the permeability transition. The action of mitochondrial respiratory substrates in preventing the permeability transition induced by Ca2+ and phosphate was examined; pyruvate, isocitrate, and glutamate proved to be particularly effective. The effect of substrates was evident also in the presence of an uncoupler, and, in addition, they were able to counteract the swelling stimulated by acetoacetate and tert-butylhydroperoxide. In the presence of various pyridine nucleotide-dependent substrates, mitochondria are able to reduce the disulfide 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) to an extent far larger than that calculated from the theoretical amount of total mitochondrial thiol groups, indicating the occurrence of a catalytic system. Similarly, the enzymes of the mitochondrial matrix in the presence of either NADH or NADPH are able to reduce DTNB. The results are discussed considering the existence of a close redox communication between pyridine nucleotides and membrane thiol groups, possibly mediated by dithiols such as thioredoxin and lipoic acid. PMID- 7771789 TI - Sublethal levels of oxidant stress stimulate multiple serine/threonine kinases and suppress protein phosphatases in Jurkat T cells. AB - Sublethal concentrations of reactive oxygen intermediates including H2O2 can alter human T cell function and inhibit proliferative responses but relatively little is known about the effects of low levels of oxidant stress on signaling pathways. In the present study, we investigated whether the exposure of Jurkat T cells to micromolar concentrations of H2O2 might influence the activity of certain serine/threonine kinases and protein phosphatases important for T cell signaling as well as initiation of nuclear events. Jurkat cells treated with 100 200 microM H2O2 exhibited rapid increases in cytosolic protein kinase C (PKC) activity without detectable translocation of PKC to the membrane/particulate compartment. The stimulation of PKC activity by H2O2 was associated with an increase in the activation of kinases phosphorylating myelin basic protein (MBP), a substrate for mitogen-activated protein (MAP) kinase and RRLSSLRA (S6 peptide; a substrate for the approximately 90-kDa ribosomal S6 kinases). Optimal activation of MAP kinase in cells treated with H2O2 was preceded by increases in protein tyrosine phosphorylations and occurred at sublethal concentrations of H2O2 which did not markedly deplete intracellular ATP. Pretreatment of cells with the PKC inhibitors sangivamycin and H7 suppressed but did not block the stimulation of MAP kinase activity in response to H2O2 or phytohemagglutinin. The activities of both protein tyrosine phosphatase (PTP) and protein phosphatase 2A (PP2A) were reduced after H2O2 treatment of intact cells. Furthermore, kinetic studies showed that H2O2 was capable of suppressing the activities of PTP and PP2A before inducing optimal increases in MAP kinase activity. These results demonstrate that the exposure of T cells to sublethal levels of oxidant stress acutely stimulates the MAP kinase cascade and suggest that this activation may involve PKC-dependent and -independent pathways as well as inhibition of certain protein phosphatases. PMID- 7771790 TI - Three-dimensional reconstruction of the hemocyanin of the protobranch bivalve mollusc Nucula hanleyi from frozen-hydrated specimens. AB - The didecameric hemocyanin of the bivalve mollusc Nucula hanleyi, observed in the electron microscope in vitreous ice, was subjected to a three-dimensional (3D) reconstruction by the random conical tilt series method. The 3D volume was analyzed by computing solid-body surface representations and slices through the volume and by eroding the structure progressively. The molecule was reconstructed from 288 and 63 images in the side- and end-on view orientations, respectively. It comprises three parts: one cylindrical wall composed of 10 oblique wall units and two collar complexes located at both ends of the cylinder and made up each of five arches and one annular collar. Erosion of the volume reveals that the wall looks like a segment of a five-stranded right-handed helix and that each oblique wall unit resembles a figure 8 inclined to the right. The 3D volumes reconstructed from Helix pomatia and N. hanleyi hemocyanins look perfectly similar, except that when the threshold is expressed as a function of the molecular volume left apparent, the various connections between the wall, the arches, and the collar disappear at a lower threshold in N. hanleyi than in H. pomatia. Conversely, with thresholds expressed as a fraction of the dynamic range of the 3D volume, the two structures are quite similar. This behavior means either that the molecular weights of Helix and Nucula hemocyanins (and therefore their molecular volumes) are not so different as indicated in the literature or that all the portions of Nucula hemocyanin have molecular weights lower than those of Helix hemocyanins. PMID- 7771791 TI - The electrochemistry of 5-hydroxybenzimidazolylcobamide. AB - Methanogenic archaea typically contain 5-hydroxybenzimidazolylcobamide (cba-HBI) as the prosthetic group of a number of methyltransferases involved in their central metabolic pathways. In this paper the (acidic) dissociation constants and standard oxidation-reduction potentials of the Co3+/Co2+ and Co2+/Co1+ couples of isolated aquo-cba-HBI were measured. Comparison of the data to those established for 5,6-dimethylbenzimidazolylcobamide (cobalamin) showed that the 5 hydroxybenzimidazolyl (HBI) nucleotidic base hardly affected the redox potentials. HBI, however, proved to be the weaker ligand, thus favoring "base off" formation. The implications for the functioning of cba-HBI in biochemical methyl group transfer reactions are discussed. PMID- 7771792 TI - Import of subunit VII of the cytochrome bc1 complex into yeast mitochondrial. AB - The import of subunit VII, the so-called ubiquinol binding protein of the cytochrome bc1 complex of yeast mitochondria, has been investigated by subcloning the gene for subunit VII into the expression vector pSP64. The precursor to subunit VII synthesized in vitro by a transcription/translation system had the same molecular weight as the mature form of this protein present in mitochondria, confirming earlier reports that subunit VII does not contain a cleavable presequence. The subunit VII precursor was imported efficiently into a protease resistant compartment of isolated yeast mitochondria in a reaction dependent upon a membrane potential and the presence of ATP both in the mitochondrial matrix and in the extramitochondrial space. After import, the radiolabeled subunit VII was bound to the mitochondrial inner membrane through protein-protein interactions and could not be detected in the matrix fraction or in the intermembrane space. Subunit VII was also imported into mitoplasts, where the protein was associated with the inner membrane facing the matrix side of the membrane. By contrast, after import into mitochondria obtained from yeast cells lacking cytochrome b, subunit VII was localized in the supernatant fraction, suggesting that the presence of cytochrome b may be required for the association of subunit VII with the inner mitochondrial membrane. PMID- 7771793 TI - What does ozone react with at the air/lung interface? Model studies using human red blood cell membranes. AB - We exposed human red blood cell (RBC) membranes to low levels of ozone and measured the oxidative damage that occurs to the proteins and the unsaturated lipids that are present. Oxidative damage to proteins causes significant decreases in the content of thiol groups, the fluorescence of protein-tryptophan residues, and the activity of membrane-bound acetylcholinesterase. Oxidative damage to lipids causes changes in some of the unsaturated fatty acids (UFA) in the lipid fraction of these RBC membranes. Significant amounts of hexanal, heptanal, and nonanal are formed from the ozonation of UFA. Although no decrease in the amount of oleate is detected, it does undergo ozonation to yield nonanal; thus, as would be expected, product appearance is a more sensitive measure of ozonation than is substrate disappearance. These results imply that both proteins and unsaturated lipids undergo simultaneous and competitive ozonation in human RBC membranes when ozone is the limiting reactant. The ratios of reaction of ozone with different targets can be predicted in reasonably good agreement with the observed values using calculations (W. A. Pryor and R. M. Uppu (1993) J. Biol. Chem. 268, 3120-3126; R. M. Uppu and W. A. Pryor (1994) Chem. Res. Toxicol. 7, 47-55) that take into account the reactivities and relative amounts of protein and lipid functionalities present in the RBC membranes. Similar calculations are used to predict the reaction of ozone with unsaturated lipids and proteins at the air/lung interface, and both UFA and proteins are predicted to react with ozone in the lung, as in RBC membranes. PMID- 7771794 TI - Isolation and characterization of a new cDNA clone belonging to the cytochrome P450 2C gene subfamily in hamsters. AB - Cytochrome P450s are heme-containing proteins which evolved from an ancestral gene to form a large superfamily of enzymes. We previously isolated three distinct CYP2C cDNAs, namely CYP2C25, 2C26, and 2C27, from liver cDNA libraries of male and female Syrian hamsters. In the present study, we isolated another cDNA clone, assigned as CYP2C28, from the same male cDNA library. This cDNA consisted of 1556 nucleotides and encoded a polypeptide of 490 amino acids. CYP2C28 showed relatively low identities to other hamster CYP2C forms (71.4-72.6% in amino acid sequences) and showed the highest similarity to rat CYP2C24 (88.7%), while the other hamster CYP2C forms showed high similarities among themselves (> 90.2%). CYP2C28 protein expressed in yeast catalyzed the N demethylation of aminopyrine and benzphetamine, but did not catalyze the hydroxylation of tolbutamide, testosterone, and progesterone. Northern blot analysis demonstrated that CYP2C28 mRNA was expressed in hamster livers 1 week after birth, when the other hamster CYP2C forms were not detectable. The level of CYP2C28 mRNA increased to 3 weeks and then decreased with time in males. The level in females was lower than that in males. In adult hamsters, CYP2C28 was induced almost threefold by administration of phenobarbital but not affected by 3 methycholanthrene. On the other hand, administration of pregnenolone 16 alpha carbonitrile induced CYP2C28 in females but not in males. These results indicate that CYP2C28 is a unique form in the hamster CYP2C subfamily. PMID- 7771795 TI - Metabolic fate of platelet-activating factor in the rat enterocyte: the role of a specific lysophospholipase D. AB - The metabolism of platelet-activating factor (PAF) by isolated rat intestinal epithelial cells was investigated using 1-[3H]octadecyl-2-acetyl-sn-glycero-3 phosphocholine. The principal metabolite produced by the cells was 1-O alkylglycerol, which was found in association with the cells and the medium. When similar studies were conducted employing an intestinal epithelial cell line (INT 407), PAF was almost quantitatively converted into 1-alkyl-2-acyl-sn-glycero-3 phosphocholine (AAGPC). When the intestinal epithelial cell microsomes were incubated in the presence of fluoride to inhibit phosphohydrolase activity, the formation of 1-alkylglycerol was decreased in association with a stoichiometric increase in 1-alkyl-glycerophosphate, indicating the presence of a lysophospholipase D in the intestinal cells. When the phospholipase D activity was examined in the microsomal fraction prepared from intestinal epithelial cells, lyso-PAF was the preferred substrate and only trace amounts of lyso-PAF were converted into alkylacyl-GPC. Acyllyso-GPC was rapidly cleaved to form free fatty acids. The absence of lysophospholipase D activity in INT 407 cells cannot be attributed to the absence of brush border in these cells since no lysophospholipase D activity was present in isolated brush border preparations. PMID- 7771796 TI - Molecular cloning and sequence analysis of flavastacin: an O-glycosylated prokaryotic zinc metalloendopeptidase. AB - A new zinc metalloendopeptidase that cleaves peptides on the amino-terminal side of aspartic acid was isolated from the cultural filtrate of Flavobacterium meningosepticum. The gene for this new enzyme was cloned into pBluescript, and the complete nucleotide sequence was determined. Over 40% of the deduced amino acid sequence was verified independently by direct protein microsequencing. The most important structural features of this new enzyme include (i) the presence of an unusual O-linked oligosaccharide of unknown function located at a unique consensus site near the C-terminus and (ii) a characteristic extended zinc binding site and corresponding Met-turn that places this metalloendopeptidase in the astacin family. This is the first example of a prokaryotic enzyme related to the eukaryotic astacin group; it is being designated hereafter as flavastacin. PMID- 7771797 TI - Glucocorticoid and sex hormones as activating or modulating factors for expression of Cyp2b-9 and Cyp2b-10 in the mouse liver and hepatocytes. AB - The effects of male and female hormones as well as glucocorticoid upon the expression of Cyp2b-9 and Cyp2b-10 were investigated in C57BL/6 mouse liver and hepatocytes in primary culture. Their expression in the untreated female liver was higher than that in the male liver. More Cyp2b-9 mRNA than Cyp2b-10 was present in the female than in the male liver, whereas the levels of Cyp2b-10 were higher in the male. Phenobarbital increased Cyp2b-10 expression more than that of Cyp2b-9 in both sexes. Treatment with beta-estradiol also induced both in the male liver, with more Cyp2b-10 than Cyp2b-9 being found. In the female liver beta estradiol and testosterone slightly increased the levels of Cyp2b-10, whereas the expression of Cyp2b-9 was reduced. Ovarectomy did not reduce the expression of the two mRNAs, but rather increased them. Using the spheroid culture system, in which mouse hepatocytes were cultured as multicellular aggregates and in which both mRNAs were expressed for a number of days, beta-estradiol as well as phenobarbital potently induced mRNA in hepatocytes from either sex and the inducibility at 10(-5) M corresponded to 10(-3) M phenobarbital. The expression level of Cyp2b-10 mRNA by phenobarbital or beta-estradiol was higher than that of Cyp2b-9, as observed in vivo, and > 10(-7) M beta-estradiol induced both in vitro. Dexamethasone induced the expression of more Cyp2b-10 mRNA than Cyp2b-9, and it was necessary for the expression by either phenobarbital or beta estradiol. The expression was not enhanced in vitro by concomitant exposure of beta-estradiol and phenobarbital. Among the other female hormones tested, estrone induced Cyp2b-9 and Cyp2b-10 mRNAs at levels equivalent to those induced by beta estradiol, and estriol and progesterone had a lower potential for the induction. Male hormones, such as androstenedione and testosterone, also had inducing potency in vitro. However, testosterone concentration dependently reduced the expression in cells cultured without dexamethasone. Tamoxifen or cryproterone, having antiestrogenic or antiandrogenic effects, respectively, also induced Cyp2b 9 and Cyp2b-10 mRNA. The suppressive effect of growth hormone on the expression of the mRNA was slight. The observation that endogenous hormones altered the expression of Cyp2b-9 and Cyp2b-10 in vivo and in vitro suggested that male and female hormones, as well as glucocorticoid, play activating or modulating roles in the constitutive expression of P450s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771798 TI - Mechanism of glycogenin self-glucosylation. AB - Glycogenin, the proposed initiator of mammalian glycogen biosynthesis, transfers glucose residues from UDP-glucose to an oligosaccharide chain attached to Tyr-194 in a self-glucosylation reaction. Mutation of Tyr-194 to either Phe or Thr residues results in the loss of this self-glucosylating activity since the site of oligosaccharide attachment has been lost (Y. Cao, A. M. Mahrenholz, A. A. DePaoli-Roach, and P. J. Roach (1993) J. Biol. Chem. 268, 14687-14693). We describe here that Phe-194 and Thr-194 mutants of glycogenin, as well as wild type protein, were active in transferring glucose to an exogenous acceptor, maltose, a known inhibitor of the self-glucosylation reaction. The reaction product was exclusively maltotriose with no evidence for further elongation to maltotetraose or maltopentaose. The values of Vmax/Km for maltotriose synthesis for the mutant proteins were 1.5-3.5 times greater than that of the wild type. Analysis of crystals of wild-type glycogenin by X-ray diffraction gives a tetragonal unit cell of a = b = 130 A and c = 174 A in space group I4 with four glycogenin molecules in one asymmetric unit. Considerations of the symmetry and the crystal packing indicate the existence of dimers of glycogenin which may further associate to form a tetramer. The existence of oligomeric forms of glycogenin, together with the idea that glucose transfer to an exogenous acceptor is possible, raises the possibility that the intramolecular self-glucosylation of glycogenin could involve an intersubunit transfer of glucose. PMID- 7771799 TI - Bacterial production and characterization of ATP11, a yeast protein required for mitochondrial F1-ATPase assembly. AB - ATP11 is a nuclear gene product that is required for assembly of mitochondrial F1 ATPase in the yeast Saccharomyces cerevisiae. ATP11 is synthesized in the yeast cytoplasm with an N-terminal targeting sequence. Following import into mitochondria, the leader sequence is cleaved, generating the functional form of the protein. ATP11 is present in small amounts in yeast mitochondria, which has made it difficult to study its role in F1 assembly. We have developed a bacterial expression system for the overproduction of the mature form of ATP11 and its biotinated derivative, BTATP11. Yeast complementation assays showed that the DNA fragments used to produce ATP11 and BTATP11 in bacteria encode biologically active proteins. The recombinant proteins produced in bacteria were purified to homogeneity and their physical characteristics were shown to be similar to those of the mitochondrial ATP11 protein synthesized in yeast. PMID- 7771800 TI - The amino acid sequence of the pancreatic islet mitochondrial glycerol phosphate dehydrogenase is not unique and the enzyme is not thyroid or glucose responsive. AB - The mitochondrial glycerol phosphate dehydrogenase (mGPD) is one of several proteins that are abundant in the pancreatic islet. Hormonal and nutritional influences confer tissue-specific patterns of expression on many of these proteins and the primary amino acid sequence of these proteins in the islet often differs from those in other tissues. However, the deduced amino acid sequence of the rat islet mGPD was identical to that of testis and liver. (The islet mGPD also possesses calmodulin-like calcium-binding sequences.) Islet mGPD activity and amount of protein were not changed by culturing islets at various concentrations of the insulin secretagogues, glucose, leucine, glutamine, or methyl succinate, which are conditions that alter the amounts of other enzymes in the islet. Unlike mGPD in tissues, such as liver, where mGPD activity is low, the high amount of islet mGPD was not further induced in hyperthyroid rats or by adding T3 to cultured islets or rat insulinoma cells. This suggests that the islet mGPD is under different regulation than the enzyme in tissues where its activity is low. PMID- 7771801 TI - Reversal of multidrug resistance phenotype by surfactants: relationship to membrane lipid fluidity. AB - Previous studies have suggested that multidrug resistance (MDR) reversal by polyoxyethylene surfactants involves alterations in plasma membrane lipid physical state of resistant cells as one of the possible mechanism(s). To date, however, a detailed and critical examination of the relationship between membrane lipid fluidity and MDR reversal by these surfactants has not been performed. In the present studies, therefore, a series of experiments were conducted to critically examine the role of membrane lipid physical state in MDR reversal by employing a unique class of clinically important nontoxic lipophilic surfactants and the KB-8-5-11 drug-resistant cell line. MDR reversal was assessed by rhodamine-123 uptake. The effect of surfactants on plasma membrane lipid fluidity of these cells was assessed utilizing a fluorescence polarization technique with fluorophores DPH, TMA. DPH, 2-AS, and 12-AS. Our studies demonstrated that: (i) in vitro addition of active MDR-reversing surfactants (Solutol HS-15, Tween 40, and Cremophor EL, 10 micrograms/ml each) decreased lipid fluidity of isolated crude plasma membranes of resistant cells; (ii) the inactive surfactants (octylglucoside, hecameg) failed to influence membrane lipid fluidity; (iii) cells grown in the presence of active surfactants also exhibited a decreased plasma membrane lipid fluidity as measured with intact cells utilizing the probe TMA.DPH; and (iv) active surfactants did not influence lifetimes of the excited state of the fluorophores. These findings demonstrate that decrease of the plasma membrane lipid fluidity of KB 8-5-11 resistant cells may be one of the important mechanism(s) of MDR reversal by polyoxyethylene surfactants. PMID- 7771803 TI - Nucleotide recognition by histone H1 involves specific protein structures. PMID- 7771802 TI - Comparison of the primary structure of nuclear and mitochondrial glutamate dehydrogenase from bovine liver. AB - Glutamate dehydrogenase (GDH) from bovine liver nuclei was compared to bovine liver mitochondrial GDH. The nuclei were isolated in sucrose buffer and sonicated, and glutamate dehydrogenase activity was extracted with 0.1 M potassium phosphate buffer. The enzyme was purified by ammonium sulfate fractionation, heating, gel filtration, affinity chromatography, and absorption chromatography to homogeniety. Nuclear GDH had the same apparent molecular weight on SDS-PAGE as mitochondrial GDH. The overall charge was slightly more negative. Cyanogen bromide and tryptic peptides of bovine nuclear and mitochondrial glutamate dehydrogenase were separated by HPLC reverse-phase chromatography using a linear gradient of 0-60% acetonitrile. Only about half of the nuclear and mitochondrial peptides had the same retention time. Several nuclear peptides from the tryptic digest were sequenced. Eight of the amino acids differed from the published sequence of mitochondrial GDH (of 99 that were sequenced). The amino acid composition of one peptide was determined and it contained 4 (of 37 amino acids) that were different from the published composition of the corresponding peptide from bovine mitochondrial GDH. The composition data agree with the sequence data from this peptide. We conclude that GDH does exist in bovine liver nuclei and that it probably differs by less than 10% in amino acid sequence from mitochondrial GDH. PMID- 7771804 TI - Proton translocation linked to the activity of the bi-trans-membrane electron transport chain. AB - Recently we have proposed and presented evidence suggesting the existence of a "bi-trans-membrane" electron transport chain, located at the contact sites between outer and inner mitochondrial membranes, which can be utilized to promote either the oxidation of exogenous NADH in the presence of catalytic amounts of added cytochrome c or the reduction of exogenous cytochrome c supported by the oxidation of respiratory substrates present inside the mitochondria. Here we show that the oxidation of exogenous NADH is accompanied by a net alkalinization of the incubation medium preceded by a transient acidification phase. In oxygen pulse experiments, the alcohol oxidation (induced by the addition of alcohol dehydrogenase) was used to mimic a cytosolic source of reducing equivalents. Oxygen pulses promote an acidification-alkalinization proton cycle which is insensitive to antimycin and myxothiazol inhibitory effect, is stimulated by valinomycin, inhibited by trypsin-aprotinin complex, abolished by the protonophore carbonyl cyanide-p-trifluoromethoxy phenylhydrazone (FCCP), and is absent or at least inverted (alkalinization-acidification cycle) in broken mitochondria. The oxidation of cytosolic substrates, mediated by the bi-trans membrane electron transport chain, does not involve endogenous cytochrome c and is associated with a vectorial proton translocation from the inside to the outside of the mitochondria. In the out-->in electron transport pathway the components involved appear to be cytosolic reduced substrates-->NADH produced by cytosolic dehydrogenases activity-->NADH-cytochrome b5 oxidoreductase complex leaning out the external side of the external membrane-->exogenous cytochrome c- >cytochrome oxidase of contact sites-->molecular oxygen. The possible components of the in-->out pathway are matrix respiratory substrates-->primary dehydrogenases of the matrix-->Complexes I, II, and III of the respiratory chain present in the inner membrane-->NADH-cytochrome b5 oxidoreductase system of the external membrane-->exogenous cytochrome c-->additional cytosolic electron acceptors or, alternatively, cytochrome oxidase of contact sites. The two pathways can be considered a bi-trans-membrane electron channeling system which, at the level of bridges set up by the contact points between the outer and the inner mitochondrial membrane, may represent a link between the redox processes occurring inside with those present outside the mitochondrion. PMID- 7771805 TI - Accumulation of the quinonoid intermediate in the reaction catalyzed by aspartate aminotransferase with cysteine sulfinic acid. AB - The pyridoxal phosphate form of aspartate aminotransferase from Escherichia coli catalyzes the irreversible conversion of L-cysteine sulfinate to the pyridoxamine phosphate form of the enzyme, bisulfite, and pyruvate. The addition of L-cysteine sulfinate to a solution containing a high concentration of enzyme (approximately 10 microM) yields a rapidly appearing red color (lambda max = 520 nm) which decays with a rate constant which is only about 1% of kcat (2-3 s-1 versus 250 s 1 at 15 degrees C, pH 7). The red color can be assigned to the quinonoid form of the enzyme substrate complex, which accumulates under these single turnover conditions. The rate of decay of this species is dependent on that for the decomposition of beta-sulfinylpyruvate (beta-SP), the initial product of the reaction between aspartate aminotransferase and L-cysteine sulfinate. Trapping beta-SP with morpholine or malate dehydrogenase plus NADH abolishes the transient red color; therefore, the intermediate accumulates by virtue of the reverse reaction of beta-SP with the pyridoxamine phosphate form of the enzyme. The association and dissociation rate constants of beta-SP with the pyridoxamine-5' phosphate form of the enzyme are 2 x 10(7) M-1 s-1 and 400 s-1, respectively, at 15 degrees C. No red transient species is observed under these conditions when aspartate is substituted for L-cysteine sulfinate. PMID- 7771806 TI - Identification of liver endothelial cells as the primary site of IgM catabolism in the rat. AB - Rat IgMs, both monoclonal protein from ascites fluid and total serum IgM, were purified by sequential gel filtration and metal chelate affinity chromatography on immobilized zinc-iminodiacetate. Two monoclonal IgMs, IR202 and IR968, chromatographed identically on gel filtration, but required different pHs for elution from the zinc affinity column. IR202 behaved like a euglobulin, being readily precipitated in low-ionic-strength buffers, while IR968 remained soluble under these conditions. IgM was isolated from serum in 30-50% yield by chromatographic procedures similar to those used for the monoclonal proteins, and 20-30% of the isolated serum IgM was precipitable as a euglobulin. The half-life of both monoclonal and serum euglobulin IgMs was 0.8 days, while the polyclonal globulin and IR968 had half-lives of 1.8 and 2.8 days, respectively, in the rat circulation. The tissue and cellular sites of catabolism of the monoclonal IgMs were determined after labeling with the residualizing label, dilactitol [125I]tyramine. For both proteins the liver was identified as the major tissue site of catabolism, accounting for 60-80% of degraded protein in the body. When liver was fractionated into parenchymal and nonparenchymal cells (NPC), the NPC were found to account for 86 and 69% of protein recovered in liver, for IR202 and IR968, respectively. Separation of NPC into endothelial (EC) and Kupffer cell populations by elutriation centrifugation revealed that EC contained the majority, approximately 70% of total NPC radioactivity from either IgM. Based on the ratios of endocytic indices (microliter of plasma/10(6) cells/day) for each cell type, the EC also had a higher efficiency for uptake of both IgMs, approximately threefold greater, than for the fluid phase marker, polyvinylpyrrolidone, or for rat serum albumin. We conclude that hepatic EC are a major site of IgM catabolism, regardless of the heterogeneity in physical and biological properties of various IgM populations. PMID- 7771807 TI - All-trans-retinoic acid interacts synergistically with basic fibroblast growth factor and epidermal growth factor to stimulate the production of tissue inhibitor of metalloproteinases from fibroblasts. AB - This report examines the effect of all-trans-retinoic acid in combination with basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) on collagenase and tissue inhibitor of metalloproteinases (TIMP) production from human foreskin and synovial fibroblasts. When 10(-5) M retinoic acid is applied in combination with 1, 10, and 100 ng/ml of either FGF or EGF to foreskin or synovial fibroblasts, this results in a dose-dependent synergistic increase in TIMP protein production which is greater than the additive effect of the agents by up to fourfold. These responses can be inhibited by the presence of specific neutralizing antibodies to bFGF and EGF, demonstrating that they result from the presence of the growth factors and not from an experimental artifact such as bacterial endotoxin. We have also found that retinoic acid potently inhibits bFGF and EGF-stimulated collagenase protein production in both skin and synovial fibroblasts. PMID- 7771808 TI - Role of calcium and protein kinase C in the activation of phospholipase D by angiotensin II in vascular smooth muscle cells. AB - We previously showed that cultured rat aortic vascular smooth muscle cells (VSMC) possess an AT1 angiotensin (Ang) receptor coupled to the activation of a phospholipase D (PLD). AT1 receptors in VSMC are also coupled to the activation of a phosphoinositide-specific phospholipase C (PLC), mobilization of intracellular Ca2+, and activation of protein kinase C (PKC). To determine whether PLD stimulation by Ang II is the result of PLC activation and the subsequent elevation of cytosolic free Ca2+ and PKC activation, we investigated the role of Ca2+ and PKC in the activation of PLD. Chelation of extracellular Ca2+ by EGTA, blockade of voltage-sensitive Ca2+ channels, or chelation of intracellular Ca2+ with BAPTA partially attenuated PLD activation and Ca2+ mobilization in response to Ang II. However, the simultaneous chelation of extracellular Ca2+ with EGTA and intracellular Ca2+ with BAPTA completely attenuated both PLD activation and Ca2+ accumulation. Ca2+ ionophores mimicked Ang II and the combined effects of Ang II and ionophore resulted in no further stimulation of PLD activity above that observed in the presence of either agonist alone. Although the putative PLC inhibitor U73122 blocked the activation of PLD by Ang II, it also may inhibit PLD activation directly, since it attenuated both Ca2+ ionophore and phorbol 12-myristate 13-acetate (PMA)-mediated increases in PLD activity. PMA also activated PLD in VSMC in a dose-dependent manner; however, Ang II and PMA stimulation were additive. Down-regulation of PKC via exposure to phorbol dibutyrate almost completely blocked PMA-induced stimulation of PLD while it had no effect on Ang II- or Ca(2+)-ionophore-mediated increases in PLD activity. The PKC inhibitor staurosporine augmented basal PLD activity and partially inhibited PMA stimulation of PLD while it had little effect on Ang II induced increases in PLD activity. Thus, optimal Ang II stimulation of PLD is dependent on the availability of both intracellular and extracellular Ca2+ and independent of PMA-mediated effects. Furthermore, these data suggest that Ang II stimulation of PLD may occur subsequent to activation of PLC, since Ang II activates PLC and PLC is shown to be responsible for increases in intracellular Ca2- in response to Ang II. PMID- 7771809 TI - Cloning and expression of the alpha subunit of succinyl-CoA synthetase from Dictyostelium discoideum. AB - We have isolated and characterized a genomic fragment and a cDNA clone for the alpha subunit of succinyl-CoA synthetase (SCS) from Dictyostelium discoideum. The coding region predicts a protein of 310 amino acids. Direct amino acid sequence data indicate that the first 16 amino acids encoded by the cDNA comprise a mitochondrial targeting sequence. The predicted molecular mass of the mature protein is 31 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The deduced amino acid sequence of the alpha subunit from D. discoideum shows 75% identity to that from rat liver, which represents a GTP-utilizing form of SCS, and 62% identity to the Escherichia coli protein, which is an ATP-utilizing form. We have previously shown that the enzyme purified from growing D. discoideum is a GTP-utilizing enzyme. In D. discoideum, the alpha subunit is a single copy gene that is developmentally regulated. Highest levels of its mRNA are seen in growing cells, which is followed by a relatively dramatic decline at the time cells complete their aggregation program. In contrast, the level of the protein, as determined by Western blots, remains unchanged throughout development. This indicates that any developmental changes in SCS activity reflect changes in the availability of its substrates or effectors and not changes in the level of enzyme. PMID- 7771810 TI - Transatrial repair of tetralogy of Fallot. PMID- 7771811 TI - Herbert Sloan Lecture. Introduction to the Sloan Lecture. PMID- 7771812 TI - Understanding cardiac anatomy: the prerequisite for optimal cardiac surgery. AB - If advances in cardiac surgery are to continue into the twenty-first century, it will be necessary to concentrate on details of matters such as the anatomy of the heart. This will be achieved best when anatomy is described as it is observed. This approach is obscured when words are used in inappropriate fashion, or else assigned a function separate from their everyday meaning. Examples of how the congenitally malformed heart and the normal heart have been described in the past are examined within the framework of using words in their vernacular meaning. Suggestions are made to improve descriptions and understanding for the 21st century. Using the example of the "univentricular heart", it is shown how conventions debarring ventricular status to discrete chambers within the ventricular mass are, of necessity, artificial. Similar examples are used to distinguish septal from parietal structures within the heart and to elucidate the structure of some congenital malformations. For values, it is shown how proper description requires assessment of these structures in their closed as well as their open positions. Understanding of cardiac anatomy, truly a prerequisite for successful cardiac surgery, will be facilitated in future if words are used in their generally accepted sense, and if artificial conventions are avoided. PMID- 7771813 TI - The STS Cardiac Surgery National Database: an update. AB - Since inception in 1990, The Society of Thoracic Surgeons (STS) National Cardiac Database has grown rapidly. More than 1,500 surgeons working in 706 hospitals have contributed more than one half million patient records. Geographic distribution of those participating is proportional to the number of centers performing heart surgery. The STS system is in use in all 49 states where centers are operating. There has been a significant decrease in length of stay for most patients having heart operations and a modest fall in coronary artery bypass grafting operative mortality from 3.7% to 3.3% over the past 3 years. Coronary artery bypass grafting case mix also is changing nationally as evidenced by a decline of 17% in the best-risk cases and concomitant increases in those with predicted risks of 5% to 10% and greater. New uses for local data in addition to self assessment and quality assurance include development of critical clinical pathways, support for managed-care group applications, and regional use. Minnesota has established a statewide STS system and Florida is soon to follow. The key to acceptance has been a peer-reviewed risk-stratification system that continues to be refined each year. Finally, a major effort will be made this year to increase the participation of general thoracic surgeons, particularly with respect to lung cancer. PMID- 7771814 TI - Esophageal replacement by colon interposition. AB - Between 1985 and 1993, 32 patients (24 male and 8 female) underwent colon interposition for replacement of the esophagus at the Mayo Clinic. Median age was 58.5 years (range, 1 to 79 years). The colon was used because of an inadequate stomach in 27 patients (84%) and as the conduit of choice in 5 (16%). Esophageal cancer was present in 15 patients (47%). The left colon was used in 20 patients (63%) and the right, in 12 (38%). The colon was placed substernally in 19 patients (59%) and in the esophageal bed in 13 (41%). The operative mortality was 9%; cause of death was ischemic necrosis of right colon conduits in 2 patients and adult respiratory distress syndrome in 1 patient. Major complications occurred in 4 additional patients and included ischemic colitis of a right colon conduit, Roux-en-Y limb obstruction, chylothorax, and an anastomotic leak. Follow up was complete for all patients and ranged from 15 months to 7 years (median follow-up, 2.3 years). Eleven patients died during follow-up. The cause of death was metastatic esophageal cancer in 9 patients, myocardial infarction in 1 patient, and respiratory failure in 1 patient. At last follow-up, 26 of the 29 operative survivors had little or no difficulty eating. Two patients had dumping symptoms, and 1 patient had severe dysphagia. Seven patients required dilation of the esophagocolonic anastomosis. We conclude that colon interposition for esophageal replacement provides acceptable long-term function; however, early morbidity and mortality are considerable. PMID- 7771815 TI - Metastasectomy for sarcomatous pediatric histologies: results and prognostic factors. AB - We reviewed our experience of pediatric metastasectomy to define (1) morbidity/mortality in this population and (2) any preoperative or intraoperative prognostic predictors of survival. One hundred fifty-two patients with median age 19 years (range, 5 to 33 years) had 258 thoracic explorations (Ewing's sarcoma, 28; rhabdomyosarcoma, 6; nonrhabdomyosarcoma soft tissue sarcoma, 42; and osteosarcoma, 76). Resections were accomplished by 218 wedge resections, 19 anatomic resections, 14 wedge and anatomic resections, 4 wedge and chest wall resections, and 3 wedge resections/other procedures. An initial complete resection was accomplished in 121/152 patients (80%). With a median potential follow-up of 10.6 years, median survival from initial thoracotomy is 2.2 years. By the Cox proportional hazards model, three or more positive nodules (p = 0.021), histology other than osteosarcoma (p = 0.0054), and incomplete resection (p < 0.0001) were unfavorable prognostic factors for survival. Two or more positive nodules (p = 0.0049), left location (p = 0.0031), age 14 years or greater at diagnosis (p = 0.0052), or rhabdomyosarcoma (p = 0.0066) predicted shorter pulmonary progression-free survivals after resection. Nonrhabdomyosarcoma pediatric metastasectomy can yield selected long-term survival. Morbidity/mortality is low, and a complete resection, if possible, is paramount. Prognostic factors can be defined that can be used to define the limits of this therapy to the patient and family. PMID- 7771816 TI - CABG after successful PTCA: a case-control study. AB - We sought characteristics predictive of the need for operative revascularization subsequent to a successful coronary angioplasty. Through June 1993, 128 patients who had successful percutaneous transluminal coronary angioplasty (PTCA) between January 1982 and March 1989 required subsequent coronary artery bypass grafting (CABG) at our hospital. These cases were matched with 128 controls who had a successful PTCA but did not require subsequent CABG. Controls were matched to cases by the date of their initial PTCA. Before initial PTCA there were no differences between the cases and controls in terms of age, sex, prior myocardial infarction, ejection fraction, duration of anginal symptoms, hypertension, hyperlipidemia, family history, or obesity (all not significant). A greater number of cases had diabetes (35 versus 18; p = 0.009). Angiography before initial PTCA revealed that cases had a greater mean number of total lesions (4.1 versus 3.3; p = 0.002) and a higher incidence of left anterior descending and circumflex artery stenoses of 70% or greater (98 versus 75 and 57 versus 34, respectively; p = 0.006). The mean number of lesions successfully dilated was greater in cases (2.4 versus 1.7; p = 0.0001). Cases had CABG at a mean interval of 16.7 +/- 23 months. There were 17 late deaths among cases and 9 among the controls at a mean of 38.6 +/- 30 months. The survival probability at 5 years was 94.5% for controls and 87.9% for cases (p = 0.048). Initial revascularization by PTCA is followed by CABG at a brief interval in a subset of patients who have markers of more severe disease than do patients who do not require early CABG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771817 TI - Should the freehand allograft be abandoned as a reliable alternative for aortic valve replacement? AB - Cryopreserved aortic allografts were used for aortic valve replacement in 80 patients between 1986 and 1994 (infracoronary in 46 and complete root replacement in 34). Hospital mortality was 6.3% (5/80) with all deaths occurring in the infracoronary group. Three of five deaths were in patients with endocarditis and valve ring abscess. Left ventricular-aortic mean pressure gradients across the allograft valves were significantly lower for root replacement patients (mean, 9.0 +/- 6.9 mm Hg versus 18.1 +/- 8.7 mm Hg for infracoronary patients) (p = 0.0001). No patient having root allograft replacement had early echocardiographic aortic insufficiency greater than grade 1 versus 28% of those having infracoronary implantations. Late aortic insufficiency of grade 2 or greater was seen in 46% of patients having infracoronary implantation versus 17% of patients having root implantation. Nine patients had explantation of an aortic allograft (eight infracoronary and one root). Reasons for explantation were as follows: endocarditis (three infracoronary, one root), technical (three infracoronary), undiagnosed idiopathic hypertrophic subaortic stenosis (1 patient), and prolapsing infracoronary leaflet (1 patient). Actuarial freedom from grade 3 and 4 aortic insufficiency or explantation was 77% at 7 years for infracoronary implantations. We conclude that the infracoronary aortic allograft has an unacceptable frequency of late insufficiency and its use in this position should be abandoned. The substantial incidence of late endocarditis in the infracoronary (free-hand) aortic allograft was surprising.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771818 TI - Current role of surgery in Mycobacterium tuberculosis. AB - From January 1986 through December 1993, we operated on 59 patients with documented Mycobacterium tuberculosis infection. Indications for operation were as follows: multidrug-resistant tuberculosis (MDRTB) in 19 patients; bronchopleural fistula secondary to Mycobacterium tuberculosis infection in 12; massive hemoptysis in 5; destroyed lung in 7; solitary nodule in 7; trapped lung in 3; complicated cavity in 4; and empyema in 2. Sixty-five operative procedures were performed: pneumonectomy with latissimus muscle flap in 15 patients; pneumonectomy in 3; lobectomy in 16; segmental or wedge resection in 11; decortication in 5; window thoracostomy in 3; thoracoplasty with myoplasty in 4; tube thoracostomy in 4; return to operating room for bleeding in 2; Clagett procedure in 1; and drainage of a cold abscess in 1. There were no operative deaths. Major postoperative complications occurred in 5 patients. The two late deaths were in patients with MDRTB: 1 with progressive disease and massive hemoptysis and the other with a relapse of MDRTB. Of the patients operated on as part of their therapeutic regimen for MDRTB, 17 (89%) of 19 have remained culture negative. We conclude that (1) surgery still plays an important role in the management of patients with Mycobacterium tuberculosis infection; (2) surgical intervention can be performed with acceptable mortality and morbidity; (3) a variety of procedures are needed to effect cure; and (4) encouraging results in patients with MDRTB support surgical therapy in this difficult group of patients. PMID- 7771819 TI - Paraplegia after thoracotomy: report of five cases and review of the literature. AB - Paraplegia complicating thoracotomy is rare but catastrophic. This report comprises 40 cases: 5 of our cases and 35 reported cases. Our cases comprised a stab wound of the left chest (1), decortication (1), lobectomy for bronchogenic carcinoma (2), and segmental resection for tuberculosis (1). The reported cases included 25 cases following thoracotomy for thoracic pathology (bronchogenic carcinoma, 12; pulmonary tuberculosis, 7; thoracic trauma, 2; bronchiectasis, 1; peptic esophagitis, 1; neurogenic tumors, 2; and benign lung lesion, 1 and 10 cases following operation for malignant hypertension. The surgical procedures performed on the 25 patients with thoracic pathology were lobectomy (8), bilobectomy (1), pneumonectomy (7), decortication (1), thoracoplasty (1), excision of neurogenic tumors (2), drainage of tuberculous cavity (1), and Nissen procedure (1). The intraoperative factors contributing to the neurologic deficit were bleeding at the costovertebral angle (9), migration of oxidized cellulose into spinal canal (9), thrombosis of anterior spinal artery (4), epidural hematoma (2), epidural narcotic (2), metastatic carcinoma (1), and hypotension (1). This serious complication can be prevented by meticulous operation and careful hemostasis. The immediate use of tomographic scanning or magnetic resonance imaging followed by surgical decompression might avert this serious complication. PMID- 7771820 TI - Experimental supplemental vein grafting and hypoperfusion syndrome. AB - An additional saphenous vein graft (SVG) sometimes is required to the same coronary system if acute internal thoracic artery (ITA) graft flow is inadequate. These experiments were conducted to determine the consequences produced by ITA SVG dual grafting. Fourteen dogs each received two coronary grafts (without bypass, using local occlusion) to the proximal circumflex coronary artery, using the ITA and an SVG, and then the circumflex artery was ligated proximally. Simultaneous flow in both grafts was determined at rest and after pharmacologic (adenosine, phenylephrine) or physiologic (cardiac pacing) stimulation. Serial angiography was performed during the first 4 weeks after grafting to determine patency patterns of the ITAs and SVGs. In the resting heart, flow was 7.5 +/- 1.6 mL/min (17.5%) in the ITA graft and 35.3 +/- 5.2 mL/min (82.5%) in the SVG (mean +/- standard deviation [% total distal perfusion]), and the combined flow was not significantly different from the original native flow. Intravenous adenosine (0.2 mg.kg-1.min-1) preferentially increased both the total ITA flow and its fractional contribution to total distal perfusion (18.4 +/- 3.2 [31.1%]; p < 0.05 versus rest). Saphenous vein graft flow was not changed significantly (40.3 +/- 6.0 mL/min), in part due to a modest decrease in arterial pressure. In contrast, intravenous phenylephrine (0.003 mg.kg-1.min-1) decreased both absolute ITA flow and its relative contribution to distal perfusion (6.1 +/- 1.1 [10.9%]; p < 0.05 versus rest), despite an increased systemic perfusion pressure, which increased SVG flow significantly (50.1 +/- 4.8 [89.1%]; p < 0.05 versus rest).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771821 TI - Neurologic events after coronary bypass grafting: further observations with warm cardioplegia. AB - Warm heart surgery has documented myocardial protection benefit, but with an added neurologic threat. It is hypothesized that moderately hypothermic aerobic heart surgery will maintain the myocardial protection and reduce neurologic risk. This study compared 493 patients undergoing coronary artery bypass graft operations with normothermic (35 degrees to 37% degrees C) continuous blood cardioplegia and normothermic perfusion to 379 coronary artery bypass grafting patients with hypothermic (33 degrees to 29 degrees C) continuous blood cardioplegia and hypothermic perfusion to test this hypothesis. There was no difference in age, sex, prior myocardial infarction, hypertension, prior neurologic event, congestive failure, or diabetes. The hypothermic group had more reoperations (24% versus 14%; p = 0.0002), class III/IV angina (83% versus 71%; p = 0.002), a trend to more triple-vessel (54% versus 47%; p = 0.10) and left main disease (18% versus 14%; p = 0.10), lower ejection fractions (0.52 +/- 0.15 versus 0.55 +/- 0.13), more grafts placed (3.6 +/- 1.1 versus 3.4 +/- 1.1; p = 0.04), but fewer internal mammary arteries (62% versus 78%; p < 0.0001). Postoperative myocardial infarction rate was 1.2% in the hypothermic group and 1.3% in the normothermic group (p = not significant). Intraaortic balloon pump requirement was 3.4% with hypothermic and 1.4% with normothermic groups (p = 0.05). The incidence of postoperative neurologic events was significantly higher in the normothermic group (4.7% versus 1.8%; p = 0.038). The multivariate correlates of stroke were older age and normothermic cardioplegia, whereas the only multivariate correlate of death was older age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771822 TI - Pharmacologic support with high-energy phosphate preservation in the postischemic neonatal heart. AB - Milrinone improves function in failing adult hearts. This study examined its effect on immature myocardium. Using an isolated working neonatal rabbit heart preparation, we measured myocardial function, high-energy compounds, and cyclic adenosine monophosphate. Hearts were subjected to 1 hour of normothermic ischemia, 10 minutes of reperfusion with Ringer's solution, and 30 minutes of reperfusion with either unaltered Ringer's, Ringer's with dobutamine (0.1 microgram/mL), or Ringer's with milrinone (1 microgram/mL). These hearts were compared with each other, with a control group continuously perfused for 70 minutes, and with a group of hearts that were made ischemic and reperfused for only 10 minutes. There was a progressive decline in adenosine triphosphate levels measured in hearts from the groups receiving 10 and 40 minutes of reperfusion with unaltered perfusate, and cardiac output fell to 82% +/- 4% of preischemic control in the latter group. When either dobutamine or milrinone was added to the reperfusion solution, postischemic myocardial function was restored completely, and the loss of adenosine triphosphate with reperfusion was halted. Cyclic adenosine monophosphate level was highest in ischemic/40-minute reperfused hearts, and there was no measurable increase in cyclic adenosine monophosphate level in the group of hearts receiving milrinone. The mechanism of preservation of high-energy stores with inotropic agents is not known but may involve potentiation of mitochondrial oxidative phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771823 TI - Effects of intracoronary calcium chloride on the postischemic heart in pigs. AB - Whether calcium chloride (CaCl2) should be used to reverse myocardial dysfunction during cardiac operations remains a controversial issue. Calcium chloride may reduce, rather than increase, myocardial contractility and may produce exaggerated vasoconstriction in postischemic vessels in which the endothelium has been damaged. These possibilities were investigated in an open-chest porcine model that allowed control of systemic hemodynamics. Incremental doses of CaCl2 (1, 3, and 10 mg/min) were infused directly into a coronary artery before and after 10 or 15 minutes of ischemia followed by 15 minutes of reperfusion. Calcium chloride increased regional contraction, coronary blood flow, and oxygen consumption before ischemia, whereas oxygen and lactate extraction were unchanged. After ischemia and reperfusion, contraction was impaired and lactate extraction was reduced, but a similar response to CaCl2 was observed. Contraction returned to baseline values promptly after CaCl2. Thus, CaCl2 exerts a positive inotropic effect both in normal and in postischemic myocardium. Calcium chloride does not cause direct coronary constriction nor does it worsen myocardial stunning after a short period of normothermic myocardial ischemia. PMID- 7771824 TI - Does it make sense to use two internal thoracic arteries? AB - Retrospectively, the first 143 patients who were operated on with bilateral internal thoracic arteries (BITA group) were matched with 143 patients operated on with only one left internal thoracic artery anastomosed on the left anterior descending artery and additional vein grafts (LITA group) and followed up for a maximum of 8 years. At 5 years follow-up there were no significant differences in event-free survival between the groups. After 8 years, the overall survival was 96% and 92% (not significant [NS]), cardiac survival 99% and 97% (NS), angina free cardiac survival 51% and 35% (NS), infarction-free cardiac survival 95% and 78% (NS), reintervention-free cardiac survival 87% and 88% (NS), and all cardiac event-free survival 49% and 31% (NS) for the BITA and LITA groups, respectively. The incidence of late pulmonary, wound, and other complications was comparable. Cox proportional hazards analysis showed that a higher left ventricular end diastolic pressure and female sex were predictors of recurrent angina and late cardiac events. During this intermediate-term follow-up, the use of one or two internal thoracic arteries was of no value in predicting angina-free or cardiac event-free survival. PMID- 7771825 TI - Intrapulmonary reconstruction of pulmonary arteries using a heterologous pericardial roll. AB - Pulmonary artery reconstruction using a handmade heterologous pericardial roll was achieved in 5 patients with severe hypoplasia of the intrapericardial pulmonary arteries and in 9 patients with critical hilar pulmonary stenosis occurring subsequent to previous construction of a systemic-pulmonary shunt. The pericardial roll was 12 to 16 mm in diameter and was anastomosed to the pulmonary arteries through divided interlobar fissures. At the opposite end, it was fixed anteriorly to the chest wall and connected to a prosthetic tube so as to obtain a blood supply from the systemic circulation. The flow through the roll measured intraoperatively was 95 +/- 23 mL.kg-1.min-1. Postoperative catheterization showed that the mean pressure in the roll was 31 +/- 18 mm Hg. Eleven patients have subsequently undergone anatomic repair using an external conduit after 8 +/- 4 months. There were no operative deaths, but 1 patient died of esophageal bleeding after the definitive intracardiac repair. We conclude that this technique is a feasible surgical option as a part of staged operations leading to biventricular repair. PMID- 7771826 TI - Repair of anomalous pulmonary venous connection to the superior vena cava. AB - Complex forms of anomalous pulmonary venous connection to the superior vena cava (SVC) can be difficult to correct surgically. Since 1987, 11 patients have undergone repair of anomalous pulmonary venous connection to the SVC by diversion of the pulmonary venous drainage to the left atrium using a baffle with division of the SVC and reimplantation on the right atrial appendage to restore normal systemic venous drainage. Total anomalous pulmonary venous connection was present in 3 patients and partial anomalous pulmonary venous connection, in 8. All patients are alive and asymptomatic at a mean follow-up of 2.3 +/- 1.4 years. Postoperative echo-cardiograms (8 patients) revealed pulmonary venous obstruction requiring reoperation in 1 patient. No patient has clinical evidence of SVC obstruction, and all are in sinus rhythm. This is a safe and effective technique for repair of complex forms of anomalous pulmonary venous connection to the SVC, and the incidence of postoperative venous obstruction and rhythm disturbances is low. PMID- 7771827 TI - Surgical management of tricuspid malinsertion in the Rastelli operation: conal flap method. AB - From June 1986 to May 1994, 25 patients underwent the Rastelli operation for complete transposition of the great arteries with ventricular septal defect and pulmonary stenosis or atresia. Fourteen patients whose tricuspid valve chordae were normal underwent the conventional Rastelli procedure (conventional group), whereas 11 patients who had tricuspid malinsertion into the infundibular septum underwent the Rastelli operation concomitant with mobilization of the infundibular septal flap, with the tricuspid valve chordae, to the right ventricular side of the intraventricular conduit (conal flap method) (conal flap group). In relation to the mobilization of the tricuspid valve chordae, right heart function and tricuspid regurgitation were compared between the two groups. There was one early death after the conventional Rastelli procedure and no early death after the Rastelli operation with a conal flap. There was one late death in the conventional group and two late deaths in the conal flap group. The mean follow-up was 50.8 +/- 5.1 months in the conventional group and 54.9 +/- 7.5 months in the conal flap group (p = 0.43). Reoperation was necessary for 1 patient in the conal flap group during follow-up. At the most recent follow-up, all patients in both groups were in New York Heart Association functional class I. Tricuspid regurgitation was estimated from the echocardiograms. Mild to moderate regurgitation was noted in 6 patients in the conventional group and 8 in the conal flap group. However, postoperative right heart catheterization data did not show any significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771828 TI - Platelet activation in warm and cold heart surgery. AB - Recent studies suggest that patients undergoing warm heart surgical procedures have reduced postoperative bleeding. To determine if this is due to differences in platelet activation, we measured platelet membrane glycoproteins (GPIb, GPIIb/IIIa, GMP 140), platelet fragments, and platelet counts before, during, and after normothermic (37 degrees C) or hypothermic (28 degrees to 30 degrees C) cardiopulmonary bypass. Cardiopulmonary bypass was associated with a significant decrease in platelet count, platelet membrane GPIb, and platelet fragments, and an increase in GMP 140 (p < 0.05). Normothermic cardiopulmonary bypass induced an early significant increase in granulocytes, whereas this was delayed until after rewarming in the hypothermic group. Mean 24-hour postoperative blood loss was 786 +/- 226 mL in the cold group versus 547 +/- 56 mL in the warm group (p = not significant). We conclude that cardiopulmonary bypass affects platelet activation and integrity and that these changes are similar in direction and magnitude for hypothermic and normothermic techniques. PMID- 7771829 TI - Primary pulmonary artery sarcoma: a report of six cases. AB - Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis seldom is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors. PMID- 7771830 TI - Cardiovascular dynamics and dimensions after bicaval and standard cardiac transplantation. AB - Bicaval orthotopic cardiac transplantation leaving the right atrium intact has been introduced recently into clinical practice as an alternative to the standard method. To determine the effect of the surgical technique, 27 patients were studied at rest and supine exercise 19 +/- 5 months after bicaval orthotopic cardiac transplantation (group A, n = 15) and 22 +/- 7 months after standard orthotopic cardiac transplantation (group B, n = 12). Resting hemodynamics showed no difference between groups. With exercise, a significantly higher right atrial pressure was noted in group B. Echocardiographic analysis showed asynchronous right atrial contraction in 83% of group B patients versus none in group A. Resting right ventricular dimensions were significantly greater in group B (right ventricular end-diastolic diameter, 3.27 +/- 0.44 cm versus 2.88 +/- 0.35 cm [p < 0.05]; right ventricular end-diastolic area, 21.3 +/- 2.85 cm2 versus 17.1 +/- 2.01 cm2 [p < 0.005]). A higher incidence and significantly higher grade of tricuspid regurgitation were found throughout exercise in group B. The exercise duration (17.34 +/- 3.53 minutes versus 14.04 +/- 4.11 minutes [p < 0.05]) and the exercise capacity (1.17 +/- 0.25 W/kg versus 0.93 +/- 0.34 W/kg [p < 0.05]) were increased in group A. These data provide some evidence that the bicaval technique of cardiac transplantation improves cardiovascular dynamics and dimensions as well as exercise capacity. PMID- 7771831 TI - Prospective evaluation of minimal blood use for ascending aorta and aortic arch operations. AB - The feasibility, safety, and impact on postoperative hospital stay of performing ascending aorta and aortic arch operations without homologous blood transfusions have not been evaluated. Sixty consecutive patients, 38 (63%) of whom also had aortic valve replacements and 17 (28%) of whom also had coronary artery bypass grafting, were evaluated for participation in blood conservation measures. Of the 45 who were able to use blood conservation techniques, 87% (39/45) required no intraoperative and 69% (31/45) required no in-hospital homologous blood transfusions. The 30-day survival rate was 98.3% (59/60), and no patient sustained a new stroke, neurologic cognitive deficit, or infection. Multivariate analysis of the 60 patients showed that the predictors of in-hospital homologous transfusion were (p < 0.05) age, cardiopulmonary bypass time, and postoperative chest tube drainage. Preoperative autologous blood donation was associated with a significantly lower risk of homologous transfusion (p = 0.0006). Indeed, patients participating in blood conservation techniques had a significantly (p < 0.05) lower incidence of homologous transfusions, required less intraoperative shed blood washing, were extubated earlier, gained less weight, had shorter hospital stays, and were discharged in a better dyspnea functional class. Most major elective cardiovascular operations on the ascending aorta and aortic arch can be safely performed without homologous transfusions. PMID- 7771832 TI - Reoperation in patients with closed SVG and patient LITA-LAD graft: T-graft approach. AB - Selection of the bypass graft that the patient has demonstrated will remain patent and free from critical atherosclerosis is a most important part of coronary artery bypass reoperations. Sixteen patients in whom a patent left internal thoracic artery-left anterior descending coronary artery bypass graft and obstructed or closed saphenous vein grafts to other coronary arteries were visualized underwent reoperation. To reach the inadequately perfused circumflex and right coronary arteries, the right internal thoracic artery was anastomosed to the left internal thoracic artery as a T graft and then was attached to the circumflex and right coronary artery branches. All patients survived the procedure and are free from angina. There were no perioperative myocardial infarctions, and there was no suggestion of hypoperfusion by the grafts. We believe this technique may reduce the incidence of graft failure in patients undergoing reoperative coronary artery bypass grafting. PMID- 7771833 TI - Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors. AB - We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771834 TI - Pretreatment with antioxidants and allopurinol diminishes cardiac onset events in coronary artery bypass grafting. AB - Oxygen-derived free radicals constitute one part of the etiologic factors for cardiac onset harmful events. Allopurinol is able to reduce the generation of free radicals. Vitamins E and C scavenge radicals after their formation. Eighty one patients with coronary artery disease were randomized into four study groups: Group 1 (n = 20) patients had stable disease and received oral vitamin E for 4 weeks, and vitamin C and allopurinol 2 days before and 1 day after coronary artery bypass grafting. Group 2 (n = 25) consisted of their controls. Group 3 patients (n = 17) had more unstable disease and received the same medications as group 1, except that vitamin E was given only 2 days before the operation. Group 4 (n = 19) was their controls. Groups 1 and 3 had fewer ischemic electrocardiographic events and required less dopamine perioperatively than corresponding control groups 2 and 4. Group 3 had fewer perioperative infarctions and less creatine kinase-MB release than the respective controls (group 4). Plasma levels of vitamins E and C, urate, and total free radical trapping ability were considered to support the theory about the role of free radicals in reperfusion injury. Especially the unstable patients, but also patients with stable coronary artery disease requiring coronary artery bypass grafting benefit from perioperative allopurinol and vitamin E and C treatment. PMID- 7771835 TI - Traumatic tricuspid valve rupture with luxation of the heart. AB - Three patients are described with the combination of a luxation of the heart through a pericardial tear and traumatic rupture of the papillary muscle of the tricuspid valve. In only 1 patient was the dislocation of the heart suspected preoperatively. In all 3 patients operative treatment was performed with considerable delay after the accident; nevertheless, all 3 patients survived. In all cases treatment consisted of repositioning of the heart, closure of the pericardium, and valvular repair of the tricuspid valve. PMID- 7771836 TI - Clinical significance of reverse redistribution phenomenon after coronary artery bypass grafting. AB - The reverse redistribution (RR) phenomenon is a decrease in thallium 201 uptake during redistribution compared with 201Tl uptake immediately after exercise. We evaluated RR in 23 patients after coronary artery bypass grafting. Postoperative RR was present in 48% and was significantly more common in patients with a history of myocardial infarction (62%). The patients were classified according to the presence (+) or absence (-) of RR. An analysis of left ventricular wall motion showed significant improvement after coronary artery bypass grafting in the RR+ group (n = 12) but not in the RR- group (n = 11). Quantitative myocardial viability was evaluated using the defect volume ratio, mean defect severity, and defect severity index. The preoperative defect volume ratio was higher in the RR+ group than in the RR- group (p < 0.05). In the RR- group, no improvement in these indices was observed after operation. In contrast, the RR+ group showed significant improvement in all three indices (p < 0.05). These results indicate that after coronary artery bypass grafting, an adequate blood supply to the remaining myocardium may induce RR. This phenomenon, therefore, may be a significant indicator of postoperative myocardial viability. PMID- 7771837 TI - Differing protection with aspartate and glutamate cardioplegia in the isolated rat heart. AB - Aspartate and glutamate each have been shown to improve cardiac recovery after hypoxia or ischemia under normothermic conditions, but whether their effects are additive and to what extent they are modified by hypothermia has not been studied systematically. We set out to compare the individual and combined protective effects of aspartate and glutamate during cardioplegic arrest under normothermic and hypothermic conditions in the rat. Using isolated working rat hearts, functional and metabolic recovery was assessed after 0.5 hours of potassium arrest at 37 degrees C or 5 hours at 2 degrees C in control hearts (C) and in hearts in which 20 mmol/L glutamate (G), 20 mmol/L aspartate (A), or both (A + G) was added to the cardioplegic solution. Under normothermic conditions, percentage recovery of prearrest work (mean +/- standard error of the mean) was as follows: C = 31.7 +/- 2.8, G = 34.8 +/- 0.2, A = 49.6 +/- 2.8*, A + G = 53.7 +/- 2.3*. Under hypothermic conditions, the values were as follows: C = 40.4 +/- 4.0, G = 45.2 +/- 2.3, A = 59.4 +/- 1.8*, A + G = 54.1 +/- 1.2* (*p < 0.01 versus C and G). Recovery of postischemic high-energy phosphate content followed the same pattern: A = A + G > G or C. Measurement of postischemic myocardial content of amino acids showed that recovery of function and energy status correlated with maintenance of myocardial levels of aspartate (r = 0.9; p < 0.01) but not glutamate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771839 TI - Patency of an internal thoracic artery graft despite maximal competitive flow. AB - Recent evidence has suggested that competitive flow is an important factor in early graft failure. In this case report an internal thoracic artery graft was used to revascularize an acute coronary artery dissection after balloon angioplasty. Subsequent angiography 4 months later showed complete healing of the dissection, yet the internal thoracic artery graft remained widely patent in spite of the maximal competitive flow from the native coronary artery. This concurs with experimental results recently reported in The Annals regarding the physiologic adaptability of the internal thoracic artery graft to suit flow requirements and its versatility as the conduit of choice. PMID- 7771838 TI - Systemic blood activation with open and closed venous reservoirs. AB - In 20 patients undergoing coronary artery bypass grafting, we studied prospectively systemic blood activation, blood loss, and the need for donor blood when using an extracorporeal circuit equipped at random with one of two different venous reservoirs. In 10 patients we used an open venous reservoir system (ORS) consisting of a hard shell venous reservoir with an integral cardiotomy filter, and in 10 patients we used a closed reservoir system consisting of a collapsible venous reservoir and separate cardiotomy reservoir. Concentrations of complement 3a, elastase, thromboxane B2, and fibrin degradation products showed a biphasic course, especially in ORS patients. During bypass, we observed a first peak of levels of complement 3a, thromboxane B2, fibrin degradation products, and elastase, which was higher in ORS patients than in patients with the closed system, because their blood continuously contacted the foreign materials of the filter and air in the open reservoir, which was avoided in the closed reservoir. Intensive blood-foreign material contact also caused the highest (p < 0.05) hemolysis in ORS patients. The larger amount of hemolytic products in ORS patients theoretically resulted in a temporary decrease in capacity of their Kupffer cells to clear endotoxin released after aortic declamping. This theory might explain the significantly (p < 0.01) higher second peak of activated products after declamping that was observed in ORS patients. Due to increased blood activation, the largest (p < 0.001) amount of shed blood loss, greatest (p < 0.05) need for colloid-crystalloid infusion, and largest (not significant) need for donor blood were found in ORS patients (0.8 +/- 0.4 versus 0.2 +/- 0.2 units of packed cells).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771840 TI - Successful heart transplantation with acquired pulmonary artery atresia. AB - Orthotopic cardiac transplantation was performed successfully in a patient with acquired atresia of the left pulmonary artery 19 years after repair of tetralogy of Fallot. Only the right lung could be incorporated into the cardiopulmonary circulation at transplantation, resulting in transient right ventricular dysfunction, which resolved with vasodilator therapy. Perfusion of a single pulmonary vascular bed does not preclude successful heart transplantation, provided there is a low pulmonary vascular resistance and pulmonary artery architecture free of stenoses. PMID- 7771842 TI - Multiple aneurysms of the internal thoracic artery. AB - Nontraumatic aneurysms of the internal thoracic artery are rare. We report a case where multiple aneurysms of the right internal thoracic artery presented as an asymptomatic density on the chest radiograph. Operative findings and pathology are reviewed. PMID- 7771841 TI - Surgical treatment of impending paradoxical embolism through patent foramen ovale. AB - We describe the case of a patient with deep venous thrombosis who had cerebral and extremity paradoxical emboli and an intracardiac thrombus crossing a patent foramen ovale identified by echocardiography. He was treated successfully with immediate intracardiac embolectomy and closure of the patent foramen ovale. PMID- 7771843 TI - Aortopulmonary fistula: an uncommon complication in dystrophic aortic aneurysm. AB - Wall dissection is a typical complication in the evolution of Marfan aortic aneurysm and usually is associated with valve regurgitation. Formation of a fistula with adjacent structures is very uncommon. We report the case of a 32 year-old man who presented with the typical features of Marfan's syndrome, with chronic aneurysm of the ascending aorta and acute aortopulmonary fistula. Diagnosis was made preoperatively by aortography; operation was performed successfully. A review of the literature only shows a few cases of aortopulmonary fistula in atherosclerotic, syphilitic, or postendocarditis disease. PMID- 7771844 TI - Donor-acquired fat embolism causing primary organ failure after lung transplantation. AB - Technically successful bilateral sequential lung transplantation in a 40-year-old man was complicated by the immediate development of pulmonary edema on reperfusion of the allograft. Death resulted within 12 hours and was caused by the fat embolism syndrome confirmed on premortem open-lung biopsy. The donor had satisfied current selection criteria but had sustained a femoral and multiple rib fractures. This case highlights the potential risks of transplanting lungs from traumatic donors and the deficiencies in current methods of donor assessment. PMID- 7771845 TI - Complete myocardial revascularization through a right thoracotomy. AB - We report the case of a 57-year-old woman who benefited from a complete revascularization of the heart, including a circumflex marginal coronary bypass grafting, through a right thoracotomy. This approach avoids sternal wound complications that can occur after high-dose mediastinal radiotherapy and omental flap reconstruction on the sternum. PMID- 7771846 TI - Pedicled jejunal seromuscular flap for bronchocutaneous fistula. AB - We report the successful closure of a complicated bronchocutaneous fistula using a pedicled jejunal flap. The fistula, secondary to tuberculosis and irradiation, previously had been closed with a latissimus dorsi musculocutaneous flap. This initial repair failed. The recurrent fistulas were closed again using a jejunal seromuscular flap, and the chest wall defect was reconstructed with a rectus abdominis musculocutaneous flap. PMID- 7771847 TI - CABG in calcified aorta under circulatory arrest. AB - Coronary artery bypass grafting in patients with calcified aorta presents a formidable problem in terms of cannulation and proximal anastomosis with its attending risks of cerebral and peripheral embolism. Coronary artery bypass grafting without cross-clamping and proximal anastomosis to the aorta at a soft spot under circulatory arrest may be a simple and safe alternative to a difficult clinical problem. PMID- 7771848 TI - Hemolytic anemia secondary to a porcine mitral prosthetic valve leaflet dissection. AB - This is a case of a dissecting cusp of a mitral porcine xenograft causing severe hemolytic anemia in the absence of valvular dysfunction and regurgitation. Six months after valve replacement, the patient had no evidence of hemolytic anemia. A cuspal dissection between the atrial and ventricular membranes was found on histologic evaluation. PMID- 7771849 TI - Arterial switch and resection of hepatic hemangioendothelioma. AB - We report on the management of a neonate undergoing arterial switch for transposition of the great arteries and concomitant resection of a hepatic infantile hemangioendothelioma. A preoperative aortogram demonstrated the arterial supply of the hepatic hemangioendothelioma. Pulmonary artery hypertension and myocardial ischemia were noted after separation from cardiopulmonary bypass. Resection of the hepatic malformation produced an immediate reduction in pulmonary hypertension and resolution of the myocardial ischemia. The patient had an uneventful postoperative recovery. PMID- 7771850 TI - Electron beam computed tomography: use in pulmonary embolectomy. AB - Proximal chronic pulmonary emboli with severe pulmonary hypertension were diagnosed by electron-beam computed tomography and Doppler echocardiography. After successful embolectomy, repeat examinations showed normal pulmonary artery pressures and patency. Electron beam computed tomography can noninvasively identify surgically treatable pulmonary emboli. PMID- 7771851 TI - Intercostal lung hernia subsequent to harvesting of the left internal mammary artery. AB - We report a case of an intercostal lung hernia developing subsequent to harvesting of the left internal mammary artery. Intercostal lung hernia is extremely rare, with most cases reported after blunt thoracic trauma. In the absence of symptoms, this was treated conservatively. PMID- 7771852 TI - Lung reduction as bridge to lung transplantation in pulmonary emphysema. AB - We present a case of bridging to lung transplantation by means of laser ablation of emphysematous bullae in a lung transplant candidate. The patient underwent successful left single-lung transplantation 17 months after lung reduction. He is now well 3 months after transplantation. PMID- 7771853 TI - Primary amyloidoma of the chest wall. AB - Primary amyloidoma of the chest wall presents as an aggressive tumor that causes local destruction. It is best treated with wide local excision and reconstruction as required, which usually is curative. A search for occult systemic disease also is recommended. PMID- 7771854 TI - Thoracoscopic excision of a malignant schwannoma of the intrathoracic vagus nerve. AB - Malignant schwannomas of the intrathoracic vagus nerve are rare tumors. A patient underwent resection of a mediastinal malignant schwannoma of the vagus nerve using video-assisted thoracoscopy, with no recurrence at 18 months. PMID- 7771855 TI - Sinus venosus defect: single-patch repair with caval enlargement. AB - We present a single pericardial patch repair of the sinus venosus defect with anomalously connected pulmonary veins, incorporating enlargement of the superior vena cava. In our small series to date this procedure has been carried out without morbidity or mortality. Noninvasive follow-up by echocardiography and electrocardiography, over the short term, has not detected any stenosis of the venous pathways or sinus node dysfunction. PMID- 7771856 TI - Surgical technique and application of pericardial fat pad and pericardiophrenic grafts. AB - Oncologic developments in stage IIIA lung cancer and complex tracheal reconstruction have renewed interest in bronchial stump and tracheal coverage. The surgical techniques to mobilize and apply pericardial fat pad and pericardiophrenic grafts are discussed. PMID- 7771857 TI - Simplified technique of heart-lung transplantation. AB - Well-known complications of heart-lung transplantation include mediastinal bleeding and phrenic nerve injury. Conventional technique places the hila behind the phrenic nerves. We have placed the hila in front of the phrenic nerve in our last 10 patients, using direct caval anastomoses when feasible. This minimizes traction on and dissection around the phrenic nerves, and allows anterior rotation of the heart-lung block for easier hemostasis of the posterior mediastinum after implantation. PMID- 7771858 TI - Pressure-induced arterial wall stress and atherosclerosis. AB - We present the hypothesis that high wall stress and accompanying stretch, particularly that caused by arterial pressure, are the primary factors responsible for the topography of atherosclerotic lesions. In our view the pattern in the localization of atherosclerotic lesions indicates that the artery behaves as both a pressure vessel and a conduit of blood flow. The phenomenon of "stress concentration" in the artery wall is described and the area of pressure induced high stress is related to the sites of atherosclerotic plaques. Data are presented indicating that reduction of pressure-induced stress may lead to absence of atherosclerotic changes. The proposed mechanism explains the prevalence of atherosclerotic lesions at the ostia of major arterial branches, at the aortic bifurcation, at the carotid bifurcation, and in the descending thoracic aorta, and also explains the absence of atherosclerosis in the intramyocardial coronary arteries and in the intraosseal portions of the vertebral vessels and why a reduction in heart rate, blood pressure, or wall stress by external support reduces the occurrence of atherosclerosis. The effect of wall stress and stretch on atherosclerosis could be mediated by the endothelial cells, the smooth muscle cells, and the penetration of low-density lipoproteins. The comprehensive presentation made in this article could lead to a better understanding of atherosclerosis, its treatment, and its prevention. PMID- 7771859 TI - Achalasia and squamous cell carcinoma of the esophagus: analysis of 241 patients. AB - Achalasia of the esophagus is presumed by many to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. There is disagreement, however, as to the precise risk of malignant degeneration and there is no consensus as to either the need for close surveillance of achalasia patients or the surveillance technique that should be employed. A review of the available literature on the subject has disclosed a wide range of reported cancer risks in achalasia patients, from zero to 33 times that of the normal population. Cancers, when discovered, are often unresectable and the median survival when they are resectable is low. A personal experience with 241 achalasia patients treated during the past quarter of a century disclosed that 9 had carcinoma, for a prevalence of 3.7%. Carcinoma developed in 3 of these 9 while they were under our observation. This translates into one cancer per 1,138 patient-years of follow up, an incidence of 88 per 100,000 population, and a risk 14.5 times that of the age-adjusted and sex-adjusted general population. Because of the low postresection survival rate if treatment is delayed until carcinoma of the esophagus becomes symptomatic, closer surveillance of achalasia patients is recommended than has been the case. Because it seems unlikely that close endoscopic surveillance will prove to be cost-effective, periodic (every 2 to 3 years) blind brush biopsy warrants further study as a means of surveillance. PMID- 7771860 TI - 1988: unilateral high-frequency jet ventilation during one-lung ventilation for thoracotomy. Updated in 1995. AB - One-lung ventilation is indicated during thoracic operations for bronchopleural fistula, pulmonary abscess, and pulmonary hemorrhage in spite of the possibility of the development of severe hypoxemia. To evaluate methods for improving oxygen transport during one-lung ventilation, we applied high-frequency jet ventilation (HFJV) and continuous positive airway pressure (CPAP) to the nondependent lung following deflation to atmospheric pressure in each procedure, and measured the effects on cardiac output and arterial oxygenation. In each case, the dependent lung was ventilated with conventional intermittent positive pressure ventilation (IPPV). Eight patients were studied during posterolateral thoracotomy using double-lumen endobronchial tubes. HFJV or CPAP to the nondependent lung improved arterial oxygenation significantly during both closed and open stages of the surgical procedures (p < 0.008). When the chest was open, HFJV maintained satisfactory cardiac output, whereas CPAP usually decreased cardiac output (p < 0.008). There were no significant differences in mean partial pressure of arterial carbon dioxide between HFJV, CPAP, and deflation to atmospheric pressure. In conclusion, HFJV to the nondependent lung provides not only satisfactory oxygenation but also good cardiac output, thereby maintaining better oxygen transport than CPAP or deflation to atmospheric pressure, while the dependent lung is ventilated with IPPV during one-lung ventilation for thoracotomy. PMID- 7771861 TI - 1988: use of a Bayesian statistical model for risk assessment in coronary artery surgery. Updated in 1995. AB - A computerized statistical model based on the theorem of Bayes was developed to predict mortality after coronary artery bypass grafting. From January, 1984, to April, 1987, at our hospital, 700 patients underwent isolated coronary artery bypass grafting. The presence or absence of 20 risk factors was determined for each patient. The first 300 patients formed the initial database of the Bayesian predictive model, and the remaining 400 patients were prospectively evaluated in four groups of 100 each. Each group was prospectively evaluated and then incorporated into the database to update the model. There was good agreement between predicted and observed results. Bayesian theory is particularly suited to this task because it (1) accommodates multiple risk factors, (2) is tailored to one's specific practice, (3) determines individual, rather than group, prognosis, and (4) can be updated with time to compensate for a changing patient population. These flexible attributes are especially valuable in light of recent changes in the coronary artery bypass graft patient profile. PMID- 7771862 TI - Practice guidelines in cardiothoracic surgery. Ad Hoc Committee for Cardiothoracic Surgical Practice Guidelines. PMID- 7771863 TI - Thoracic Surgery Directors Association: 1994 in review. PMID- 7771864 TI - Closed mitral valvotomy: TEE probe or tactile control. PMID- 7771865 TI - A few issues involving the maze procedure. PMID- 7771866 TI - Intraoperative hematocrit and viscosity do not correlate with postoperative white blood cell count. PMID- 7771867 TI - Dissection with double arch. PMID- 7771868 TI - Balloon occlusion of the aortic valve for antegrade continuous warm blood cardioplegia. PMID- 7771870 TI - [Cooperative survey of the results of coronary surgery during cardiac rehabilitation]. AB - The aim of this study was to assess the type and frequency of cardiac and extracardiac complications of coronary artery surgery in patients referred for cardiac rehabilitation (for which it is one of the principal indications): this was a prospective study carried out simultaneously in 30 cardiac rehabilitation units during December 1992 and including 533 patients (81 women, 452 men) with a mean age of 62.1 years. The total number of coronary grafts was 1,361 (on average 2.5 per patient); the internal mammary artery was used in 87% of cases; revascularisation was complete in 66.4% of patients. One or more complications were observed in 79% of patients during the hospital period (68.9%) and/or during the rehabilitation phase (44.7%), independently of age, sex, duration of cardiopulmonary bypass, or the interval to cardiac rehabilitation. The main extracardiac complications were respiratory (31.5%), disturbances of cerebral function (15.6%) and renal failure (10.3%). Cardiac complications comprised arrhythmias, essentially supraventricular (21.3%), infarction and residual postoperative ischaemia (8.4%), large pericardial effusion (7.5%), cardiac failure (4.5%), and wound infection (4.3% including 2.8% mediastinitis). Anaemia, a secondary effect of cardiopulmonary bypass, was observed in 25% of patients. This prospective study, though affected by a bias of selection and not fully representative of the surgical outcome, shows the need for a personalised management of these patients, the early indication of cardiovascular rehabilitation contributing to the optimisation of coronary artery surgery at less cost and with improved safety. PMID- 7771869 TI - Vladimir Demikhov. PMID- 7771871 TI - [Is the quantification of mitral valve involvement by transesophageal echography useful before percutaneous mitral commissurotomy?]. AB - The aims of this study were to determine the value of quantifying mitral valve disease by transoesophageal echocardiography before percutaneous mitral commissurotomy (PMC) and to analyse the incidence of embolic complications during PMC since the introduction of transoesophageal echocardiography. From March 1987 to December 1991, 317 patients with pure or dominant mitral stenosis were selected by Doppler echocardiography to undergo PMC at the Montreal Institute of Cardiology. The clinical features of the first 138 patients (Group I) were the same as those of the last 179 patients (Group 2) who also underwent routine transoesophageal echocardiography the day before the procedure. A thrombus in the left atrial appendage was observed in 8 patients in Group 2 (4.4%). No embolic complications have occurred since the protocol was changed to include routine transoesophageal echocardiography, whereas 4 embolic episodes, 3 of which were fatal, occurred in patients in group 1. The indication of PMC was turned down because of angiographically severe mitral regurgitation which was underestimated by transthoracic echocardiography in 2 patients in Group 1 (1.4%) and in 3 patients in group 2 (1.6%). The mobility, thickness and degree of calcification of the valves were attributed a score from 0-4 at transthoracic and transoesophageal echocardiography. No difference was observed in the scores of mobility (2.3 +/- 0.5 versus 2.3 +/- 0.05, NS) or valve thickness (2.1 +/- 0.4 versus 2.1 +/- 0.4, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771872 TI - [The exercise-recovery loop and exercise slope of ST segment changes/heart rate in the diagnosis of coronary disease and restenosis after angioplasty]. AB - This study addresses the diagnostic value of two new criteria of exercise stress testing for primary coronary artery disease and restenosis after angioplasty: the slope of the linear relation between ST segment changes and heart rate during exercise; the exercise-recovery loop (clockwise direction in normal subjects and anticlockwise direction in coronary patients). These two criteria were compared with the standard diagnostic criteria (horizontal or descending ST segment depression greater than 1 mm or ascending ST segment depression greater than 2 mm) in 125 patients with suspected coronary artery disease who underwent computerised exercise stress testing and coronary angiography (30 single, 31 double and 30 triple vessel disease; 34 without significant stenosis) and in 24 patients with single vessel disease who underwent successful angioplasty and who performed exercise stress testing before, immediately after and 6 months after angioplasty before routine control coronary angiography. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) of the exercise-recovery loop for the diagnosis of coronary disease were 81 %, 82 %, 89 %, respectively, versus 69 %, 71 % and 88 % for the standard criteria. The detection of restenosis by these criteria also appeared to be better (71 %, 91% and 91 % versus 46 %, 63 % and 60 %, respectively). However, for the classical threshold value of 2.4 mv/beat/min, the ST/HR criteria seemed to be less useful (Se : 80 %, Sp : 26 %). PMID- 7771873 TI - [Production of oxygen free radicals in myocardial infarction treated by thrombolysis. Analysis of glutathione peroxidase, superoxide dismutase and malondialdehyde]. AB - Many enzyme systems such as glutathione peroxidase (GPx) or superoxide dismutase (SOD) neutralise the oxygen derived free radicals produced during myocardial reperfusion by thrombolysis. Erythrocytic SOD, plasma and erythrocytic GPx and their cofactor selenium, substances reacting with thiobarbituric acid (TBARS) were analysed by repeated sampling between T0 and 48 hours in 24 patients treated by thrombolysis for acute myocardial infarction. Angiographic control was undertaken systematically between 60 and 180 minutes after initiating thrombolytic therapy: 18 patients had a patent vessel and 6 patients had an occluded vessel recanalised in 5 cases by angioplasty. Biological analysis was performed in the 23 patients successfully revascularised by thrombolysis, eventually completed by angioplasty. The plasma GPx decreased non-significantly between T0 and 2 hours from 246.8 +/- 53.3 to 233 +/- 39 U/ml with a significant increase between 2 and 48 hours from 233 +/- 39.2 to 294 +/- 76 U/ml, whereas the erythrocytic GPx rose significantly and constantly between T0 and 48 hours from 34.8 +/- 7.1 to 37.6 +/- 7.5 U/gHb with significant consumption of selenium between T0 and 4 hours from 81.2 +/- 14 to 68.5 +/- 12.6 micrograms/l. The erythrocytic SOD increased significantly between T0 and 48 hours from 318.9 +/- 40.8 to 337 +/- 59 U/gHb. Finally, the analysis of plasma TBARS showed a non significant rise between T0 and 30 minutes from 1.59 +/- 0.30 to 1.71 +/- 1.43 mm/l with a return to the basic line values after about 2 hours. These results show a significant increase in the activity of enzymes protecting against the liberation of oxygen free radicals, such as erythrocyte or plasma GPx and erythrocyte SOD between T0 and 48 hours with consumption of selenium, cofactor of GPx, and an increase in circulating lipid peroxydes in acute myocardial infarction treated by thrombolysis. They also illustrate the oxidative stress which occurs in this situation. PMID- 7771874 TI - [Changes in heart rate after ventricular stimulation; correlations with vagal tone]. AB - The authors report a new method of studying the autonomic nervous system, especially vagal tone, during endocavitary electrophysiological studies. After termination of fixed ventricular pacing at incremental rates to 200/min, an initial acceleration of the heart rate is observed followed about 5 seconds later by a sudden slowing. This phenomenon was studied in 278 patients. Ninety seven patients had no cardiac disease: the variation in heart rate was 33 +/- 18%. In the 181 other patients with cardiac disease (ejection fraction 35 +/- 16%) the variation was only 21 +/- 16% (p < 0.01). When the ejection fraction was less than 30%, the variation was only 13 +/- 4%. When the heart rate variation was less than 10%, the prognosis was poor because, of the 48 patients with this sign, 13 died, whereas there were only 2 deaths in the 133 other patients with cardiac disease and preserved adaptation. In 14 patients without cardiac disease the injection of 2 mg of atropine suppressed all adaptation of the heart rate, whilst in 18 other patients, oral betablockers reduced the variation but it persisted to a significant degree. The authors conclude that the adaptation of the heart rate after rapid ventricular stimulation is probably a reflection of vagal tone and may be used to assess the prognosis of subjects undergoing electrophysiological investigations. PMID- 7771875 TI - [Influence of gender and size on parameters measured by signal-averaged electrocardiography in healthy subjects: preliminary study]. AB - The aim of this study was to determine the influence of electrocardiographic and biomorphometric factors on the parameters measured by signal averaged electrocardiography (SA-ECG) in normal subjects. The study population comprised 40 Caucasian students (20 men, 20 women). The SA-ECG measured 6 parameters: total duration of the averaged QRS, the root mean square of the voltage of the last 40 ms of the QRS (RMS 40) and the length duration of the terminal signal of under 40 microV (LAS), each parameter being measured with a band pass filter of 25 and 40 Hz. The echocardiographic recording included measurement of 12 parameters including left ventricular mass and ventricular volumes. Five morphological parameters were measured, including height, weight and body surface area. The duration of QRS measured with a 25 Hz band pass filter was significantly longer by 9.7 ms in men than in women (102.9 +/- 8.5 ms versus 93.2 +/- 8.1 ms; p < 0.001). Similarly, QRS duration measured with the 40 Hz band pass filter was longer in men by 11.4 ms than in women (102.1 +/- 9.6 ms versus 90.7 +/- 7.5 ms; p < 0.001). Multiple linear regression analyses showed that in both men and women, the duration of the QRS measured with either a 25 or 40 Hz band pass filter was correlated to size: the taller the subject, the longer the QRS duration. A negative correlation was observed between size and RMS 40 measured with both 25 and 40 Hz band pass filters: the taller the subject, the smaller the value of RMS 40.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771876 TI - [Value of permanent cardiac pacing in hypertrophic and obstructive cardiomyopathies resistant to medical treatment]. AB - The authors report their experience of long-term dual-chamber pacing in the treatment of hypertrophic and obstructive cardiomyopathy. Between August 1990 and March 1993, 16 patients (8 men, average age 53.5 +/- 18.9 years, range 21 and 79 years) with symptomatic hypertrophic obstructive cardiomyopathy resistant to medical therapy underwent electrophysiological investigation to assess atrioventricular conduction and the effects of temporary atrioventricular pacing on the intraventricular pressure gradient before implantation of a dual-chamber pacing system. The decision to implant was taken if the endocavitary studies showed severe atrioventricular conduction defects and/or if temporary pacing reduced the systolic pressure gradient by more than 30%. Temporary dual-chamber pacing led to a decrease of 48% of the systolic pressure gradient from 78.6 +/- 21.3 to 40.1 +/- 23.6 mmHg (p < 0.0005), a regression observed in 15 of the 16 patients. After an average follow-up period of 18.7 +/- 9.5 months (range 6 and 37 months), all 15 patients who received a dual-chamber pacing system were alive and were clinically improved. The systolic pressure gradient continued to decrease during the follow-up period (24.4 +/- 17.2 mmHg at the 6th month compared with 36.5 +/- 18.6 mmHg at the time of implantation; p = 0.014). The clinical improvement was dependent on careful adjustment of the atrioventricular delay which was programmed at relatively short values (65.6 +/- 14 ms, range 47 and 75 ms) to obtain permanent right ventricular capture. The authors conclude that dual-chamber pacing is an effective means of treating symptomatic hypertrophic obstructive cardiomyopathy resistant to medical therapy, even in the absence of preexisting conduction defects. PMID- 7771877 TI - [Surgical plasty of the coronary trunks: an alternative to bypass techniques]. AB - Between January 1991 and December 1993, surgical coronary angioplasty was performed in 12 patients with an average age of 59 years: right coronary artery (17), left main coronary artery (3) and bilateral angioplasty (2). Internal mammary or gastroepiploic artery bypass grafts were associated on another vessel in 5 patients and 1 patient also underwent aortic valve replacement. There was no early mortality (1 month), or perioperative myocardial infarction. At the 15th postoperative day, the angiographic result was satisfactory in all patients. At 6 months, exercise testing was negative in all cases (maximum load 140 +/- 20 watts). Reoperation for bypass surgery was necessary in 1 patient because of symptomatic occlusion of the left anterior descending left anterior descending artery, one year after angioplasty of the left main coronary extending to the proximal left anterior descending. With a mean postoperative follow-up of 19 +/- 7 months (6 to 31 months), all patients are asymptomatic: 5 of the 6 angioplasties controlled angiographically at 1 year were patent without any signs of progression (1 occlusion/reoperation). Surgical angioplasty of the main coronary vessels is a sure and reliable procedure: it restores physiological coronary perfusion, economises venous and arterial vessels and is no obstacle to percutaneous transluminal coronary angioplasty. PMID- 7771878 TI - [Cardiac tamponade disclosing neoplasm: apropos of 23 cases]. AB - The authors report a series of cardio-pericardial metastases presenting acutely with tamponade. There were 14 men and 9 women with an average age of 39 years. The primary tumour was mainly bronchial in the men (5 cases: 20.8%) and breast (3 cases: 16.6%) or uterine (4 cases: 16.6%) in the women. The other malignancies were blood dyscrasias (5 NHL and 1 MHL) one pericardial mesothelioma, one Schwannoma, one Ewing's sarcoma and one carcinoma of the larynx. The primary tumour was not found in one case. Echocardiography showed a large, circumferential pericardial effusion in all cases and compressing the right heart chambers (RA and/or RV) in half the cases. Rounded echogenic masses implanted on the pericardial membranes (2 cases) or images of false membranes (10 cases) were also demonstrated. The clinical emergency led to pericardiocentesis with surgical drainage in 5 cases. A pleuro-pericardial window was fashioned in 4 cases. The effusion was important in all cases and bloody in 75% of cases. Cytology of the pericardial liquid was positive for malignant cells in 1 out of 2 cases. The diagnosis was made after death in 3 cases. The other biopsies, bronchial, lymph node, pleural and bone marrow also provided valuable diagnostic information. Undifferentiated carcinoma was found in 75% of bronchial carcinomas. In all three breast tumours, the histology showed moderately well differentiated adenocarcinoma. The authors underline the paucity of therapeutic measures: at this stage, pericardiocentesis is almost the only procedure apart from the cases of haemopathy. Some authors have suggested radiotherapy of the precordial region and others, intrapericardial chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771880 TI - [Physiopathology of mitral mechanics in hypertrophic cardiomyopathy. Groupe de travail "Cardiomyopathies et insuffisance cardiaque" de la Societe Francaise de Cardiologie]. AB - Ventricular hypertrophy, the only indisputable phenotypical marker of hypertrophic cardiomyopathy, is the basis of the physiopathology and treatment of the disease. Mitral valve abnormalities are usually considered to be secondary to the hypertrophy but the genesis of systolic anterior motion by the Venturi effect has been questioned by many clinical and experimental observations. Abnormalities of the mitral valve apparatus may in themselves (elongation of the valves, antero internal malposition of the mitral papillary muscles and/or hyperlaxicity of antero-internal corhdae tendinae) create systolic anterior motion or subaortic obstruction in the absence of septal hypertrophy and/or increased subaortic flow velocities. Anatomo-clinical studies have confirmed this hypothesis: a high prevalence of mitral valve disease (increased valvular surface and length) has been found in hypertrophic cardiomyopathy. The recognition of these abnormalities is of value from the therapeutic (mitral valvuloplasty) diagnostic (in borderline cases) and genetic (when the primary nature of the abnormalities is confirmed) points of view. PMID- 7771879 TI - [Automatic implantable defibrillators; subdiaphragmatic insertion]. AB - Although the material and techniques of implantation of the electrodes of implantable defibrillators have been improved, the abdominal implantation of the generator remains widely used as described by Mirowski in 1980. Despite a progressive reduction in their size, the generators remain bulky and a source of local complications. The risks and discomfort of implantation in the abdominal wall led the authors to try subdiaphragmatic implantation in 22 patients. There was no morbidity with perfect healing in all 22 cases. The mean follow-up period was 11 months. The patients felt very comfortable, a significant advance with respect to abdominal implantations. PMID- 7771881 TI - [Functional capacity after cardiac transplantation]. AB - Cardiac transplantation has transformed the prognosis of NYHA Class IV severe cardiac failure. However, despite a "new heart", the exercise tolerance of transplanted patients remains poor for a long time. Cardiac denervation which decreases the chronotropic reserve, diastolic left ventricular dysfunction and intrinsic muscular abnormalities related to lack of training and to treatment are the underlying causes. PMID- 7771882 TI - [Primary ventricular fibrillation and early recurrence: apropos of a case of association of right bundle branch block and persistent ST segment elevation]. AB - The authors report the case of a 36 year old man who presented with an early recurrence of primary ventricular fibrillation. The initial investigations were normal apart from the finding of complete right bundle branch block with persistent ST segment elevation in the right precordial leads. The recurrence was observed 6 weeks after the initial diagnosis which led to the implantation of an automatic defibrillator. This clinical case is similar to a syndrome recently described of sudden death without obvious cardiac disease but with right bundle branch block and ST segment elevation. PMID- 7771883 TI - [Syncopal angina caused by sinus arrest; cured by transluminal coronary angioplasty and calcium inhibitor]. AB - The authors report the case of a 42 year old man who smoked and who presented with recurrent spontaneous anginal chest pain followed by syncope due to sinus arrest. The mechanism underlying these symptoms was spasm of the left circumflex artery at the site of severe stenosis of its middle segment just before the origin of the sinus node artery. Treatment with a calcium antagonist with transluminal coronary angioplasty of the narrowed segment of the circumflex artery resulted in complete regression of all symptoms with a follow-up of 15 months. Seven other reports of the same type were found in the literature concerning 6 men and 1 woman, with an average age of 49 years, presenting with the same symptoms and sinus arrest associated with the minimal coronary artery disease. The proof of coronary spasm was documented in 6 of the 7 cases by a positive ergometrine stress test or by the observation of spontaneous spasm during coronary angiography or rapid atrial pacing. The outcome was good with calcium antagonist therapy in 5 cases, and with slow release nitrate derivatives in 1 case. One patient, treated by betablockers, died. It is useful to investigate some sino-atrial blocks to diagnose the underlying ischaemic mechanism as the patients may be treated simply with calcium antagonists rather than undergo implantation of a pacemaker. PMID- 7771884 TI - [A rare clinical form of angioneurotic edema caused by enalapril: acute abdomen]. AB - The authors reports an unrecognised secondary effect, but perhaps not as rare as has been thought, of enalapril: the acute abdomen. Three similar cases have previously been reported. The underlying mechanism is probably the inhibition of degradation of tissue kinins to inactive peptides as in subcutaneous and/or submucous angioneurotic oedema. Todate, this secondary effect has not been reported with other angiotensin converting enzyme inhibitors. The relationship between the acute abdomen and angioneurotic oedema with primary hyperaldosteronism is discussed. PMID- 7771885 TI - [Cardiopulmonary exercise evaluation: value and influence of the use of a ramp protocol versus triangular protocol]. AB - The aim of the study was to evaluate a ramp bicycle ergometer exercise protocol consisting of a very small but rapid increase in load (2 watts/12 seconds) for direct measurement of the VO2 max. Eighteen sedentary healthy subjects were in Group I (16 men, mean age 29 +/- 6 years) and 10 men with chronic stable cardiac failure in Group II (mean age: 51 +/- 16 years). All subjects performed two exercise tests within a period of 8 days, one with a ramp protocol (protocol R) and the other with a standard triangular exercise protocol (protocol T) of 30 watts/3 minutes for Group I and 20 watts/2 minutes for Group II. All procedures were performed until the subjects were exhausted. Direct measurement of VO2 max was performed by rapid response analysers enabling a cycle to cycle study. The parameters were measured and compared by a paired Student t test at each stage of the test: at rest, at submaximal exercise (third level), at anaerobic threshold and at maximal exercise. There was no significant difference between VO2 max and VO2 at the threshold of ventilation between the two populations. An increase in carbon dioxide production at different stages was observed with the ramp protocol. Furthermore, the highest maximal respiratory quotient and anaerobic threshold appeared earlier in Group II with the ramp protocol. Therefore, with respect to the standard triangular protocol, the ramp protocol provides comparable VO2 values. Its potential value, reported in the literature, is a better correlation between the observed and theoretical VO2 values. However, an increase in CO2 production should be underlined, probably related to greater recruitment of anaerobic metabolism in the absence of a steady state. This may be the reason for attaining the anaerobic threshold earlier. PMID- 7771886 TI - [Complications of percutaneous mitral valvuloplasty; comparison of the double balloon and the Inoue techniques]. AB - Percutaneous mitral valvuloplasty is a non-surgical procedure for treating mitral stenosis. There are two techniques of performing this procedure, the double balloon and the Inoue techniques. The aim of this study was to compare the immediate complications of percutaneous mitral valvuloplasty in two consecutive series of unselected patients undergoing the double balloon (131 patients) and the Inoue (131 patients) techniques. The two series were comparable before valvuloplasty with respect to demographic, clinical, echocardiographic and haemodynamic criteria. The increase in valvular surface area and the decrease in pressure gradient after valvuloplasty were not significantly different (1.1 +/- 0.2 to 1.95 +/- 0.5 cm2 in the Inoue series and 1.0 +/- 0.2 to 1.95 +/- 0.5 cm2 in the double-balloon series; 12 +/- 3 to 5 +/- 2 mmHg in the Inoue series and 13 +/- 4 to 5 +/- 2 mmHg in the double-balloon series for the mean transvalvular pressure gradient). A good immediate result was defined as a valve surface are > 1.5 cm2 and < or = 2 + mitral regurgitation after the series, and this was obtained in 78% of cases in both series. Severe mitral regurgitation (3 +) requiring immediate or elective mitral valve replacement was observed in 7 cases in the Inoue series and in 5 cases in the double-balloon series (NS). One cerebral embolism occurred in the double balloon series and two systemic embolisms, one cerebral and one coronary, in the Inoue series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771887 TI - [Long-term hematological management of cyanotic congenital heart diseases]. AB - The long-term management of cyanotic congenital heart disease requires treatment of raised haematocrit (> 65%) whilst conserving the quality of the red blood cells [mean corpuscular volume, mean corpuscular haemoglobin concentration (MCHC)]. Since 1975, the author has chosen chemotherapy (hydroxyurea, pipobroman) as first-line treatment, reserving iron supplements, phlebotomy and platelet antagonists as adjuvant therapy. Pre-treatment data of 170 patients showed: a high prevalence of hypochromic microcytosis due to iron deficiency and of thrombopaenia, in relation to the severity and duration of the polycythaemia. Hyperuricaemia was greater than 420 mumol/l in 67% of cases; effort tolerance and hyperviscosity were related to the haematocrit and iron deficiency. One hundred and forty seven patients were followed up for a total duration of 769 years of chemotherapy. Clinical tolerance was good: biological tolerance was marked by a high frequency of thrombocytopaenia requiring withdrawal (10 cases) or reduction of treatment (34 cases). The causes of the 39 deaths observed are analysed: none was related to the hydroxyurea or pipobroman. The treatment or follow-up was stopped in 29 cases: the reasons are reported. Seventy eight patients under treatment had a favourable outcome with normal social reinsertion in 74 cases. This efficiency was related to maintenance of a haematocrit < 65%, to correction of the iron deficiency and increase in the MCHC. These results were obtained with an average dosage of 19 +/- 4.5 mg/kg/day of hydroxyurea (69 patients). By slowing erythropoiesis, chemotherapy reduces the indication of phlebotomy, so reducing iron loss: it also inhibits excessive bouts of polycythaemia in cases of iron therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771888 TI - New FDA guidelines on the treatment of hypertension: comparison of different therapeutic classes according to trough/peak blood pressure responses. AB - The FDA guidelines, recommending a trough/peak blood pressure response ratio of at least 50%, were formulated with a view to providing a definitive index of duration of action of an antihypertensive drug. The aim was to prevent the use of drug regimens that utilised high doses of drug with the aim of maintaining a significant reduction in blood pressure at the end of the steady state dosage interval. The calculation of trough/peak ratios is subject to significant variability but much of this can be directly attributed to different methodological approaches. However, when conditions are standardised it has been shown that trough/peak ratios are reproducible in individual patients. Trough/peak ratios defined for different antihypertensive drugs often exhibit as many differences within a therapeutic class as between therapeutic classes. Thus there is no single therapeutic class of drugs that offers high trough/peak ratios compared to an alternative class. The possible exception to this are the diuretics which probably all have comparatively high trough/peak ratios although this has never formally been defined. With respect to the beta adrenoceptor antagonists there is discernible discrimination between the once a day agents with betaxolol, bisoprolol and acebutolol all having a longer duration of action as defined by a higher trough/peak response than atenolol. Calcium antagonists show considerable variability in trough/peak ratio between different drugs. In particular the first generation agents, verapamil, nifedipine and diltiazem all had relatively low values. Not all the second generation agents were superior to this and at present only amlodipine and lacidipine and some of the "reformulated" agents meet the recommendations of the Guidelines for once a day drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771889 TI - [Pilot study of the efficacy of ticlopidine in early patency of coronary endoprostheses]. AB - Subacute thrombosis of coronary stents is the main complication of this technique. The authors studied the outcome of 387 patients and 400 coronary arteries who underwent implantation of 427 stents between December 1989 and February 1994 and followed up one month after the procedure: all patients receive 500 mg of ticlopidine daily from three days before angioplasty throughout the hospital period and continued for at least one month. Anticoagulation with heparin was undertaken by the intravenous route after implantation and relayed with subcutaneous heparin for one week until control coronary angiography performed in the first 300 patients. At one month, 96.9% of patients were free of clinical coronary events. The following major complications were observed: 5 deaths (1.3%), 5 Q wave myocardial infarctions (1.3%); no emergency bypass surgery. The peripheral vascular complication rate was 3.6%. Univariate analysis three risk factors of subacute thrombosis: age (p = 0.0058), arterial diameter of less than 3 mm (p < 0.01) and implantation for occlusive dissection (p = 0.03). Multivariate analysis showed two independent risk factors: age (p = 0.001) and arterial diameter of less than 3 mm (p = 0.01). This pilot study shows a particularly low subacute thrombosis rate in unselected indications with an acceptable level of vascular complications. PMID- 7771890 TI - [Value and limitations of diagnostic function of bradycardia of a ventricular pacemaker]. AB - The indication for permanent pacing may be confirmed by a bradycardia counter in patients without ECG or Holter recording of the causal bradycardia. The algorithm was assessed in a multicenter register with the SORIN Theorema model. The activation of the device was programmed on a double hysteresis of 2 seconds with a programmable histogramme of detections and sensing and pacing counters. One hundred and forty five patients were recruited in 50 centers over 2 years: 89 men and 56 women aged 33 to 96 years (average 72 years), 87 of whom had no other obvious cardiac disease. One hundred and ten had typical syncopal episodes, 19 had atypical or minor syncopal attacks and 16 were asymptomatic, one with sinus node dysfunction and the others with pathological prolongation of the HV interval (> or = 70 ms) during endocavitary electrophysiological investigation. The mechanism of the bradycardia was considered to be infra-hisian in 62 patients who had HV intervals > or = 70 ms. This was also the probable mechanism in 20 others who had bundle branch block and typical syncope despite a HV interval < 70 ms and in 6 patients with bundle branch block and typical syncope who did not undergo electrophysiological investigation before implantation. Twenty one patients had sinus node dysfunction during electrophysiological investigation and 8 had a carotid sinus syndrome. The remaining 28 cases had transient syncope but no ECG changes or abnormality on electrophysiological investigation. Permanent pacing was proposed when an extracardiac origin of the syncope was excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771891 TI - [Long-term course after electric ablation of the bundle of His in the treatment of supraventricular tachycardia]. AB - The authors report the long term results of His bundle ablation for supraventricular tachycardia in a series of 49 patients. This retrospective study was based on a patient population of 27 men and 22 women with an average age of 59 at the time of ablation, between 1984 and 1993. The indication for His bundle ablation was invalidating supraventricular tachycardia resistant to antiarrhythmic therapy in all cases. One group of patients (Group I, n = 31 patients) underwent high energy electrical shock and the second group (Group II, n = 18 patients) recruited after 1991, underwent radiofrequency catheter ablation. Complete atrioventricular block was obtained in the first group in 1 to 4 sessions whereas 17 patients of Group II were treated in a single session. During a follow-up period of an average of 40 months, 2 patients were lost to follow-up and 6 died, 3 of cardiac failure, 1 of a cerebrovascular accident, 1 of pulmonary carcinoma and 1 of unknown cause. In Group I, atrioventricular conduction persisted in 1 patient (primary failure) and reappeared in one other patient, but, in Group II, complete atrioventricular block persisted even in the patient in whom the interruption was not obtained with a single session of radiofrequency ablation. The patients were generally physically improved and satisfied not to have any palpitations. A decrease in exercise capacity estimated by the NYHA classification was observed in 38% of patients without apparent cardiac disease who developed dyspnea. On the other hand, 43% of patients with cardiac disease and in NYHA class > or = 2 were improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771892 TI - [Results, complications and long-term follow-up of percutaneous ablation of atrioventricular conduction. Apropos of 85 cases]. AB - This retrospective study reports the immediate and long-term results of percutaneous ablation of atrioventricular conduction. Between July 1983 and January 1992, 85 consecutive patients (51 men, age 64 +/- 10 years, range 43-84 years) presenting with supraventricular arrhythmias (atrial fibrillation n = 53; atrial flutter n = 50; atrial tachycardia n = 17; junctional tachycardia n = 6) resistant to antiarrhythmic therapy (number of drugs used: 4 +/- 1.3, range 1-6) underwent interruption of atrioventricular conduction by fulguration (n = 65) or radiofrequency energy (n = 13) or by an association of the two methods (n = 7). The 75 pacemakers implanted (10 patients had pacemakers before the procedure) comprised 55 VVIR, 11 VVI, 5 DDD and 4 DDDR units. The immediate results included two sudden deaths at the 4th and 7th day in patients undergoing fulguration and three complications with a favourable outcome (staphylococcal septicaemia, pulmonary embolism and haematoma at the site of implantation of the pacemaker). None of the patients was lost to follow-up and the average follow-up was 31 +/- 18 months (range 2-108 months). During follow-up, 15 patients died and there was a recurrence of symptoms in 11 patients after 1 to 9 months requiring a repeat procedure. In the 68 survivors, the follow-up is now 38 +/- 18 months (range 12 108 months). Sixty one patients have 2nd (2) or 3rd (59) degree atrioventricular block, giving 90% good electrocardiographic results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771893 TI - [Prevalence of intra-auricular thrombi detected by transesophageal echocardiography in patients with cardiac transplants]. AB - The aim of this study was to determine the prevalence of intra-atrial thrombi or spontaneous contrast by transoesophageal echocardiography in patients who underwent cardiac transplantation by Lower and Shumway's technique. Transoesophageal echocardiography was performed in 52 transplant patients (43 men, 9 women: average age 51 years) with a high frequency biplane transducer. After surgery, all patients received platelet antiaggregant therapy. Despite this treatment, 4 patients had a sudden systemic embolic episode and were then placed on oral anticoagulants. All patients were in sinus rhythm at the time of the examination and some had signs of acute rejection on endomyocardial biopsy performed the same day. Spontaneous contrast was observed in 27 patients (52%) and was associated with thrombosis in 15 patients (29%). These thrombi were located in the left atrial appendage in 8 cases, on the left atrial posterior wall in 5 cases and on the left atrial sutures in 2 cases. None of these thrombi had been detected by transthoracic echocardiography. No significant difference was observed between those with and those without thrombosis with respect to left atrial dimensions, left ventricular ejection fraction, cardiac index, pulmonary pressures and the number of episodes of acute rejection. The 4 patients with a history of arterial embolism all had an intra-atrial thrombus. This study demonstrates a high incidence of spontaneous contrast and intracardiac thrombi in the dilated left atrium of patients transplanted by Lower and Shumway's technique. It also underlines the value of transoesophageal echocardiography in the follow-up of transplant patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771894 TI - [Oxidative stress and lipid-protein peroxidation after cardiac transplantation. New hypotheses for explaining pathogenesis of accelerated forms of ischemic heart disease]. AB - The ischaemic heart disease developed by cardiac transplant patients is characterised by its rapid onset, which accounts for a number of its special features when compared with the usual form observed in non-immunosuppressed patients. However, the two forms of the disease are basically similar, that of the transplanted patients being practically a caricature of the non immunosuppressed patients and thereby allowing a quasi-experimental model for the study of the metabolic causes of the disease which remains the leading cause of death in the world, all ages and sexes included, irrespective of the economic wealth of the countries. PMID- 7771895 TI - [Surgery for atrial fibrillation by the Cox technique. Apropos of 2 cases]. AB - The authors report the cases of two patients who underwent surgery of atrial fibrillation by Cox's technique. In one case, it was associated with mitral valvuloplasty for atrial fibrillation of 4 years' duration; sinus rhythm was restored on the 19th postoperative day; it persisted at 11 months without antiarrhythmic drugs. On the other case, it was associated with mitral valve replacement for atrial fibrillation of 7 years' duration in a patient with dilated cardiomyopathy and a poor left ventricle; sinus rhythm was restored by electrical cardioversion during the 4th postoperative month; it persisted at 9 months with antiarrhythmic therapy. Cox's technique allows: 1) definitive suppression of atrial fibrillation, 2) restoration of atrioventricular synchronisation, 3) preservation of atrial transport function. The indications are paroxysmal or permanent atrial fibrillation, invalidating and resistant to medical therapy; atrial fibrillation of over 3 years' duration associated with mitral regurgitation requiring valvular repair and atrial fibrillation of invalidating primary cardiomyopathy. PMID- 7771896 TI - [Subannular pseudoaneurysm of the left ventricle complicating mitral valve replacement; apropos of a case]. AB - The authors report the case of a 72 year old woman with a Carpentier-Edwards bioprosthesis implanted in March 1981 for severe mitral stenosis, asymptomatic until 1986. The progression of effort dyspnoea with prosthetic valve dysfunction despite digitalo-diuretic therapy and severe ventricular subannular pseudoaneurysm. Doppler echocardiography and cardiac catheterisation and angiography confirmed the mitral subannular pseudoaneurysm and led to surgical cure of this fibrous structure and implantation of a mechanical mitral valve prosthesis. This complication of mitral valve replacement is a cause of pseudoaneurysm which should not be overlooked. PMID- 7771897 TI - [Campylobacter fetus subspecies fetus endoaortitis on a Bentall tube prosthesis. Apropos of a case]. AB - Campylobacter fetus is a rare cause of endocarditis and endoaortitis: the authors believe this to be the second reported case of infection of an intracardiac prosthesis. The patient was a man who had already undergone replacement of the aortic valve and ascending aorta, and a gastrectomy, which were predisposing factors. The portal of entry was not found. The diagnosis was confirmed by positive blood cultures and transoesophageal echocardiography. The outcome was rapidly fatal despite antibiotic therapy and surgery, because of the seriousness of the lesions (pseudo-aneurysm of the aorta ruptured into the right atrium), the precarity of the terrain and surgical difficulties. PMID- 7771898 TI - [Fissuration of thoracic aneurysm in Horton disease, favourable course after surgery]. AB - The authors report another case of rupture of the thoracic aorta in Giant Cell arteritis. The progressive nature of the rupture enabled life-saving aortic replacement with a vascular prosthesis. Only one previous report of this type of operation was found in a search of the literature. The prevalence of aortitis in Giant Cell arteritis would appear to be underestimated after autopsy studies. It affects the thoracic aorta mainly in the ascending segment but sometimes involves the whole aorta. It may remain asymptomatic or be complicated by arterial occlusion, aortic regurgitation, aneurysm, dissection or rupture. Effective steroid therapy could prevent these complications. PMID- 7771899 TI - [Technical problems posed by automatic treatment of arrhythmia by an implanted pacemaker]. AB - The automatic treatment of arrhythmias by cardiac pacemakers requires a phase of recognition of the arrhythmia followed by its treatment. Different factors limit the analysis and recognition ranging from the quality of detection of spontaneous events to the recognition of the arrhythmias. Bipolar dual chamber pacing is essential: it allows minimisation of the detection of interference or cross talk between the atrial and ventricular chambers and better discrimination of episodes of rapid rhythm. The treatment algorithms are multiple, difficult to investigate in the laboratory, and their efficacy varies with the evolution of the pathology or with medical treatment. There is not a single response but a programme where the antitachycardia modes of pacing succeed one another until the reduction of the arrhythmia. This instability of treatment implies a capacity of memorization with a double objective: to authorize a posteriori diagnosis of the treated pathology and to analyse the evolution of the antitachycardia response. These diagnostic functions are also dependent on the quality of detection and pacing. The automaticity of the treatment, when essential, can only be envisaged in patients available for strict and regular clinical follow-up. PMID- 7771900 TI - [Treatment of supraventricular arrhythmia by permanent cardiac pacing]. AB - Most pacemakers are used for the treatment of bradyarrhythmias. However, a small number of pacemakers has been implanted for the treatment of supraventricular tachycardia resistant to medical therapy. The results of small reported series show long-term pacing to be effective in terminating reentrant atrial and junctional tachycardia. This has led to an improved quality of life and fewer hospital admissions in the majority of patients. Although there are a number of limitations to the widespread use of this mode of treatment, the development of pacing techniques has improved our understanding of the mechanism of termination of tachycardia which has been fully used in ventricular tachyarrhythmias. In addition to the curative treatment of sustained junctional tachycardia, pacemakers have been implanted to prevent the occurrence of new episodes with seemingly equally satisfactory results. However, cardiac pacing for this indication is much less common now because of the very good results obtained recently by radiofrequency ablation techniques. The prevention of atrial arrhythmias, vagally-induced atrial tachyarrhythmias and the bradycardia tachycardia syndrome are good indications for permanent pacing. The prevention of atrial fibrillation in sinus node dysfunction by pacing is becoming more popular with the emergence of new modes (DDI and rate-adjusted modes) and original arrhythmia preventing algorithms. The discussion about the real efficacy of atrial pacing in sinus node dysfunction is disappearing as results of prospective randomised trials confirming this efficacy become available, especially in preventing atrial fibrillation. PMID- 7771901 TI - [Permanent atrial resynchronization by synchronous bi-atrial pacing in the preventive treatment of atrial flutter associated with high degree interatrial block]. AB - Interatrial conduction block results in a very delayed and retrograde activation of the left atrium and is associated with a high incidence of atrial tachyarrhythmias, especially a particular (and specific) form of atypical atrial flutter. Electrophysiologic studies have suggested that these arrhythmias were usually due to reentry and could be directly related to the conduction disturbances in the atrium. If so, we can expect reasonably that permanent atrial resynchronization resulting from simultaneous pacing in different target sites in the atria, may not only correct for interatrial dysynchrony, but also may significantly contribute to prevent arrhythmia recurrences. Twenty-eight patients, mean age 68 years, were included. The mean P wave duration in spontaneous sinus rhythm was 181 +/- 28 ms. In all patients, many recurrences of atrial tachyarrhythmia were documented, especially a specific form of atypical atrial flutter. Medical therapy was constantly ineffective. Three different pacing modes were used: 6 patients, with normal A-V conduction were implanted with a SSI device, programmed in AAT mode and connected, using a Y bifurcated connector, to two atrial leads, one positioned in the right atrium, the second one into the coronary sinus-in 14 patients, with A-V conduction defects, a conventional DDDR unit was implanted and connected to a composite biatrial electrode and a ventricular lead. In that configuration atrial resynchronization was only effective on paced atrial cycles -a specific DDD Chorus ELA Medical device with a special algorithm loaded into the RAM memory was implanted in 14 patients (8 new indications, and 6 patients first implanted with a DDDR unit). RESULTS: during sinus rhythm atrial resynchronization induced a reduction of the P wave duration from 181 +/- 28 ms to 116 +/- 12 ms. During permanent pacing the mean value decreased from 209 +/- 38 ms to 108 +/- 13 ms. During follow-up (34 +/ 15 months) arrhythmia prevention was assessed by history, by monthly surface ECG's and by bimonthly 24 hours Holters recordings and telemetric interrogation of the pacemaker statistics. Twenty-one patients did not experienced any recurrence of arrhythmia. One to three recurrences occurred in the other seven patients, including six patients implanted with a conventional DDDR unit. These preliminary results seem validate the new concept of atrial resynchronization for prevention of atrial arrhythmia associated with interatrial conduction block. PMID- 7771902 TI - [Radiofrequency catheter ablation: theoretical and technical aspects]. AB - Radiofrequency currents produce circumscribed tissue necrosis by progressive and localised heating. Endocardial application via the percutaneous approach with a specific electrophysiological catheter enables destruction of the anatomical substrate of many cardiac arrhythmias. The technique is well tolerated due to the absence of barometric phenomena and general anaesthesia, and the possibility of modulating the energy delivered, which explains why it has supplanted fulguration in most indications. The technological evolution aims to increase the lesional power and decrease the number of complications. This implies the development of catheters capable of delivering greater currents without the risk of thrombus formation and of generators dependent on electrical or thermal parameters. The low incidence of complications reported by centres using the technique is based on an excellent understanding of the technique, the use of appropriate material, the surveillance of parameters which allow detection of unwanted effects and the respect of a strict operation protocol. In the absence of these precautions, the wide diffusion of this technique, favored by its low cost and relative simplicity, may be associated with an increase in the number of side effects which could be lethal. This cannot be accepted in a technique with such wide indications, including arrhythmias with a usually benign long-term prognosis. PMID- 7771903 TI - [Intracardiac treatment of atrial flutter by radiofrequency currents]. AB - Though not as common as atrial fibrillation, atrial flutter is frequently encountered in everyday cardiological practice. Though generally thought to be benign, it may be difficult to treat both in respect to its conversion to sinus rhythm and prevention of recurrences. It is often poorly tolerated. There are resistant, invalidating forms for which catheter ablation of the His bundle may be considered as a last resort. This is only a palliative measure even if effective from the functional point of view. A new technique for treating atrial flutter by a direct action on the atrial tissue has been recently introduced. The basis of this method is the concept of circus movement of the activation in the right atrium, the wave front circulating in an anti-clockwise direction in common atrial flutter. The postero-inferior region of the right atrium, at Koch's triangle, is the site of slow conduction and the target of choice for catheter ablation. The detection of this zone is determined by the endocavitary recording of fragmented, prolonged electrogrammes and by atrial stimulation techniques. The application of radiofrequency currents on these bases (high energy shocks are rarely used nowadays) results in interruption of atrial flutter. However, there are no data available concerning the long-term efficacy of this technique. Since 1992, our group has used an anatomical approach for catheter ablation. This aims to apply the radiofrequency current on the isthmus of atrial tissue between the orifice of the inferior vena cava and the tricuspid annulus through which the flutter wave front passes to reach the interatrial septum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771904 TI - [Ablation of the accessory pathways by radiofrequency currents]. AB - The introduction of ablative methods has revolutionised therapeutic strategy in cardiac arrhythmias. Accessory pathways are the most commonly targeted arrhythmogenic substrate. Several parameter may be used to determine the optimal site of ablation: accessory pathway potential, atrioventricular interval, atrial or ventricular pole of the pathway, morphology of the unipolar wave. The localisation of the accessory pathway sometimes requires specific techniques. The success rate reported in the literature is generally over 90%. However, the number of applications of radiofrequency current varies according to the authors from an average of three to eight. A combination of "timing related" criteria and direction of activation and the use of infraliminal stimuli minimise the number of radiofrequency applications. The incidence of complications in multicenter registers is 5% and the relapse rate is 8%. The long-term effects of catheter ablation are unknown, especially when used in childhood. A certain reserve should be maintained in the indications of ablation. Only high-risk, life-threatening arrhythmias, or those resistant to pharmacological intervention, are formal indications. Other (so-called "convenience") indications depend on the express wish of patients clearly informed of the advantages and risks of this method. PMID- 7771905 TI - [Catheter ablation of atrioventricular nodal reentrant tachycardia]. AB - Electrophysiological data of atrioventricular nodal reentrant tachycardia recensed over the last 40 years in the animal and in man has not resolved the question as to the exact site of the reentry circuit: an exclusively intranodal pathway or a pathway involving part of the atrium? The remarkable efficacy of modern radical therapy of this arrhythmia with preservation of atrioventricular conduction reinforces the concept of reentry involving not only the atrioventricular node but also the juxta nodal atrium and the superior and inferior atrionodal connections. Radical treatment was initially surgical and then by catheter ablation. The technique of specific ablation of the rapid anterior pathway was the first to be described. Its limitation is the relatively high risk (about 10%) of complete atrioventricular block. Very quickly, radiofrequency ablation of the slow posterior pathway became the method of reference. Most patients do not have retrograde conduction in the slow pathway. The pathway is located in sinus rhythm by recording its specific potentials: either the rapid potential described by Jackman et al or the fragmented potential described by Haissaguerre and Warin. The former is recorded from the posterior septal position anterior to the orifice of the coronary sinus; the second is recorded at the same level but slightly above in the mid septal position. Ablation of the slow pathway can be performed on these purely anatomical criteria. Using these approaches, an immediate success rate of over 90% may be obtained. The recurrence rate is 0 to 5%; that of complete atrioventricular block ranges from 0 to 4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771906 TI - [Choice of the mode of stimulation after ablation of the bundle of His. Experience based on a retrospective survey of 192 patients]. AB - A retrospective study of 192 patients centered on the outcome of supraventricular arrhythmias after catheter ablation of the atrioventricular junction provided some useful information concerning the choice of pacing mode in these patients. With the exception of atrioventricular bloc after ablation of the rapid nodal pathway where simple DDD pacing is adequate, rate adaptive pacing would seem to be essential. The VVIR mode should be the mode of choice in atrial flutter, permanent atrial fibrillation, poorly controlled atrial fibrillation and paroxysmal atrial fibrillation of elderly subjects (over 70 years) and/or of male sex, and/or complicating advanced cardiac disease (valvular, ischaemic or primary). The DDDR mode (with an algorithm to prevent endless loop tachycardia) is the mode of choice in sinus node dysfunction and/or in young patients (under 60), and/or females and/or in idiopathic arrhythmias and/or when retrograde VA conduction persists. When the pacemaker is replaced, the indication should be reviewed with respect to the outcome of the arrhythmia, which underlines the value of accurate implanted Holter systems. PMID- 7771907 TI - [Fulguration and radiofrequency in ventricular tachycardia]. AB - Eighty-nine cases of ventricular tachycardia, resistant to antiarrhythmic therapy, were treated over a 10 year period by high energy D ablation (fulguration). This series included 37 cases of myocardial infarction with a mean ejection fraction of 30%. The mean follow-up period of the survivors was 61 months and clinical efficacy was 87.9%. Twenty-three cases of arrhythmogenic right ventricular dysplasia, aged 40 years, and with an ejection fraction of 57%, followed up for 71 months, had a clinical efficacy of 83%. Twelve patients had verapamil sensitive (fascicular) ventricular tachycardia. Their age was 30, their ejection fraction 65%, the follow-up period 55 months, and the clinical efficacy was 100%. Ten patients had primary dilated cardiomyopathy. Their age was 35, their ejection fraction 23%, the follow-up period of 38 months with a clinical efficacy of 80%. Four patients, aged 21, had operated congenital heart disease with an ejection fraction of 60%, a follow-up of 36 months and a clinical efficacy of 100%. Finally, 3 patients had idiopathic infundibular ventricular tachycardia. Their age was 36, the ejection fraction 62%, the follow-up period was 72 months and the clinical efficacy was 67%. Non lethal complications were observed in 16% of cases, mainly haemopericardium requiring pericardocentesis in 4.5% of cases. The operative mortality and in the month following ablation was 9.2%, observed mainly during the learning period. These results show that fulguration is not without risk, but in skilled hands, it gives remarkable results in the majority of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771908 TI - [Clinical aspects of implantable defibrillators: indication]. AB - The rapidity of technological progress has now made available a device which was only a dream a few years ago, a nearly ideal implantable defibrillator. Despite the persistence of a number of technical and clinical problems, the fourth generation defibrillators are multiprogrammable, with antitachycardia and antibradycardia functions, implantable by the endocavitary approach in most cases thanks to the introduction of biphasic shocks, fitted with constantly improving systems of telemetry, and are progressively smaller in size. The selection of a defibrillator device requires consideration of the patient's needs and the technical characteristics of the defibrillator. Apart from special situations in which the indications of the implantable defibrillator are generally accepted, it is only possible in the absence of results of prospective clinical trials, to use data accumulated on the place of defibrillation compared with other forms of management of severe ventricular arrhythmias. As there is a wide choice of treatment of these ventricular arrhythmias, the role of each must be defined for each individual patient. With regards to the implantable defibrillator, it is essential to take into consideration a number of clinical and paraclinical factors such as the clinical preservation of the arrhythmia, the underlying cardiac disease, left ventricular function and the type of arrhythmia induced by programmed ventricular stimulation. PMID- 7771909 TI - [Automatic implantable defibrillators: long-term results]. AB - The automatic implantable defibrillator is an essential component of the preventive management of sudden death of patients with malignant ventricular arrhythmias. Though its efficacy in this indication is not contested, the data concerning its influence on global cardiac mortality is more controversial. The elements of this controversy are reviewed. Several prognostic factors are implicated, the principal of which being the patient's haemodynamic status as assessed by objective evaluation of left ventricular function. Prospective randomised studies comparing medical therapy with the automatic implantable defibrillator are under way and should provide a better understanding of its indications in the future. PMID- 7771910 TI - [Surgery for arrhythmias]. AB - The role of surgery in the treatment of cardiac arrhythmias has been marginalized in recent years with the rise in eminence of radiofrequency current ablation especially in the Wolff-Parkinson-White syndrome and nodal reentrant tachycardia. The indications of antiarrhythmia surgery for ventricular arrhythmias have become standardised. The unquestioned efficacy of the surgical techniques proposed (endarterectomy or cryosurgery with or without peroperative mapping) should not be associated with unacceptable mortality rates as when left ventricular function is too poor, implantation of a defibrillator is always possible. In the domain of atrial fibrillation, the interventions proposed (corridor or maze procedures) do not have the foundations that the follow-up of a sufficient number of cases would confer but they have the merit, especially the latter, of taking the underlying physiopathological mechanisms into consideration. PMID- 7771911 TI - [Lesions caused by techniques of endocavitary ablation using high frequency currents: anatomo-pathological aspects]. AB - Anatomopathological studies have considerably increased our understanding of the ablative technique by radiofrequency current. They have provided information on the nature, extent and time dependency of the lesions induced. Despite variable results according to whether the experiments were performed in vitro or in vivo, a correlation has been observed between the volumes of the lesions and the energies used. One factor is unquestionable: monitoring the temperature allows better control of the lesion size than monitoring current intensity. However, other technical points are essential for this control such as ensuring good contact between the catheter and the endocardium and the definition of the optimal surface area of the electrode. Now that the conditions of efficacy and security of ablation by high frequency currents are known, anatomopathological studies in man have become rare. These studies, which will take a long time to perform due to the very nature of the technique and pathologies treated, should provide interesting anatomo-electrical comparisons to increase our understanding of certain arrhythmias. PMID- 7771912 TI - The role of methylphenidate in psychiatry. PMID- 7771913 TI - A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. AB - BACKGROUND: There are few controlled studies of methylphenidate hydrochloride in adults with attention-deficit hyperactivity disorder (ADHD), and their results have been equivocal. The discrepancies among these studies may be related to low doses, diagnostic uncertainties, and lack of attention to comorbid disorders. METHODS: We conducted a randomized, 7-week, placebo-controlled, crossover study of methylphenidate in 23 adult patients with DSM-III-R ADHD using standardized instruments for diagnosis, separate assessments of ADHD and depressive and anxiety symptoms, and a robust daily dose of methylphenidate hydrochloride, 1.0 mg/kg per day. RESULTS: We found a marked therapeutic response for methylphenidate treatment of ADHD symptoms that exceeded the placebo response (78% vs 4%, P < .0001). Response to methylphenidate was independent of gender, psychiatric comorbidity with anxiety or moderate depression, or family history of psychiatric disorders. CONCLUSION: Robust doses of methylphenidate are effective in the treatment of adult ADHD. PMID- 7771914 TI - Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. AB - BACKGROUND: The findings from case reports and patient questionnaire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder. METHODS: Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylphenidate hydrochloride (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and using rating scales completed by the parents, teachers, and physician. RESULTS: Methylphenidate effectively suppressed hyperactive, disruptive, and aggressive behavior. There was no evidence that methylphenidate altered the severity of tic disorder, but it may have a weak effect on the frequency of motor (increase) and vocal (decrease) tics. CONCLUSION: Methylphenidate appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder. PMID- 7771915 TI - Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. AB - BACKGROUND: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites. METHODS: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain. RESULTS: The uptake of [11C]methylphenidate in the brain was high (mean +/- SD, 7.5% +/- 1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [11C]methylphenidate, was identical to that of [11C]cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [11C]methylphenidate from striatum (90 minutes) was significantly slower than that of [11C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain. CONCLUSION: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration. PMID- 7771916 TI - Family-environment risk factors for attention-deficit hyperactivity disorder. A test of Rutter's indicators of adversity. AB - BACKGROUND: This study investigated whether family-environment risk factors are associated with attention-deficit hyperactivity disorder (ADHD). Compelling work by Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, and foster care placement) rather than the presence of any single factor that led to impaired development. Based on the work of Rutter, we hypothesized a positive association between indicators of adversity and the diagnosis of ADHD and ADHD-associated impairments. METHODS: We studied 140 ADHD and 120 normal control probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years. Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well as impaired cognitive and psychosocial functioning. RESULTS: The odds ratio for the diagnosis of ADHD increased as the number of Rutter's adversity index predicted ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning disabilities, cognitive impairment, and psychosocial dysfunction. CONCLUSIONS: A positive association appears to exist between adversity indicators and the risk for ADHD as well as for its associated psychiatric, cognitive, and psychosocial impairments. These findings support the work of Rutter and stress the importance of adverse family-environment variables as risk factors for children with ADHD. PMID- 7771917 TI - In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. AB - BACKGROUND: A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax. RESULTS: Diagnostic groups differed in Bmax by analysis of variance (P < .0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r = .63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms. CONCLUSIONS: We conclude that, like schizophrenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia. PMID- 7771918 TI - Duration of neuroleptic treatment and prevalence of tardive dyskinesia in late life. AB - BACKGROUND: Although increasing age is the most consistently cited risk factor for the development of tardive dyskinesia for patients in the second to sixth decades of life, this relationship may not hold within geriatric populations. METHODS: Consecutively admitted geropsychiatric inpatients were examined with the Abnormal Involuntary Movement Scale within 72 hours of admission; comprehensive demographic, diagnostic, and psychometric data were also obtained. RESULTS: Seventy-four (19.2%) of 386 patients received diagnoses of dyskinesia. Lifetime duration of neuroleptic use was strongly correlated with dyskinesia rates. After accounting for the effect of lifetime duration of neuroleptic use in a stepwise logistic regression, only associations with Global Assessment Scale score and presence of dental problems remained statistically significant. In comparison with the duration of neuroleptic use, however, the contribution of these factors was minor. Sixteen percent of patients with less than 3 months of neuroleptic use, 29% with 3 to 12 months of neuroleptic use, 30% with 1 to 10 years of neuroleptic use, and 41% with more than 10 years of neuroleptic use had dyskinesia. Compared with patients with no history of neuroleptic treatment, the relative risks for these durations of neuroleptic use were 1.62 (95% confidence limits [CL], 0.81, 3.24), 2.89 (95% CL, 1.50, 5.55), 3.08 (95% CL, 1.66, 5.70), and 4.11 (95% CL, 2.12, 7.96), respectively. CONCLUSIONS: Within elderly populations, duration of exposure to neuroleptics is the strongest predictor of risk for tardive dyskinesia, and this risk increases rapidly within the first year of total lifetime neuroleptic use. PMID- 7771919 TI - Family study of early-onset dysthymia. Mood and personality disorders in relatives of outpatients with dysthymia and episodic major depression and normal controls. AB - BACKGROUND: The nosological status of dysthymia has generated considerable controversy. The major issues include whether dysthymia should be classified as a form of mood or personality disorder and, if dysthymia is classified as a mood disorder, whether it is sufficiently distinct from major depression to warrant a separate category. METHODS: We conducted a family study of 97 outpatients with early-onset dysthymia, 45 outpatients with episodic major depression, and 45 normal controls, and their 882 first-degree relatives. Axis I and II disorders were assessed in relatives using direct and informant interviews and all available medical records. RESULTS: The rate of major depression in the relatives of early-onset dysthymic probands was significantly greater than in the relatives of normal controls and non-significantly greater than in the relatives of episodic major depressive probands. The rate of dysthymia was significantly greater in the relatives of dysthymic probands than in relatives of both major depressive probands and normal controls. Rates of most personality disorders were increased in the relatives of the dysthymic and major depressive probands compared with relatives of normal controls. In addition, the relatives of dysthymic probands had significantly higher rates of any personality disorder and any cluster B disorder than those of episodic major depressive probands, although these differences disappeared after controlling for Axis II comorbidity in the probands. Finally, dysthymic probands with and without a lifetime history of major depression did not differ on rates of psychiatric disorders in relatives. CONCLUSIONS: There is a strong familial relationship between dysthymia and major depression. However, dysthymia is also somewhat distinct in that it aggregates specifically in the families of patients with dysthymia. Finally, dysthymia and episodic major depression both appear to have a familial association with the personality disorders, although the link appears to be somewhat stronger for dysthymia. PMID- 7771920 TI - The prevalence of dementia and depression in the elderly community in a southern European population. The Zaragoza study. AB - BACKGROUND: Provocative international disparities reported in the prevalence rates of dementia and depression require further investigation. This is the first psychiatric study, to the best of our knowledge, about the prevalence of DSM-III R dementing and depressive disorders and their relationships in a representative, stratified community sample of the elderly in both a Spanish-speaking country and southern Europe. METHODS: A two-stage screening was completed in 1080 elderly. Sampling with replacement was done, and the cumulative response rate was 88%. In phase 1, lay interviewers administered the Spanish versions of the Mini-Mental State examination and the Geriatric Mental State Schedule-Automated Geriatric Examination for Computer Assisted Taxonomy package. In phase 2, research psychiatrists administered the same instruments and the History and Aetiology Schedule to all the probable cases and a similar number of randomly selected, probably normal subjects. RESULTS: An estimated 5.5% of the elderly were considered to have a dementing disorder, the most prevalent types being primary degenerative dementia, Alzheimer's type (4.3%), and multi-infarct dementia (0.6%). Depressive disorders were found in 4.8% of the elderly. Psychiatric morbidity, specifically depression, was associated with lower educational levels. "Case levels" of depression were documented in 25.4% of the demented cases and case levels of "organic" disturbance were seen in 18.2% of cases of major depression. CONCLUSIONS: Among the elderly, the prevalence of Alzheimer's disease and multi-infarct dementia, as opposed to depression, increases steeply with age. The overlap found between dementia and depression may have nosological implications. There could be an effect of lower education levels on psychiatric morbidity, particularly on depression. PMID- 7771921 TI - Clozapine-associated postoperative ileus: case report and review of the literature. PMID- 7771922 TI - The prevalence of schizophrenia in Ireland: readdressing the enigma. PMID- 7771923 TI - [Lymphoepithelial organs in the local immunity system of the mucous membranes]. AB - The review deals with modern concepts of morphofunctional organization of lymphoepithelial organs relating to the lymphoid tissue associated with mucous membranes of the gastro-intestinal and respiratory tracts. They are unique among the peripheral immunogenesis organs due to their combination of lymphopoietic function with a function of the mucous membrane immunity. Their peculiar feature is their border location and close interrelation with epithelium which is an obligatory participant of the immune response. PMID- 7771924 TI - [Peripheral primitive neuroectodermal tumors of the soft tissues and bones]. AB - Large group of small-round-cell tumours of soft tissues and bone represents a complex diagnostic problem for the pathologists. Neuronal nature of many tumours from this group is proven by means of new methods--immunophenotypic analysis, tissue culture, cytogenetics. Peripheral neuroepithelioma, Ewing tumour, primitive neuroectodermal tumour (PNET), Askin tumour belong to these neoplasms. These tumours anatomically have no connection with the structures of the central nervous system or autonomous sympathetic nervous system. PMID- 7771925 TI - [Malignant chondroblastoma of bone (variants in its structure and histological diagnosis)]. AB - 16 tumours developing mainly in the adult patients are studied histologically. Several morphological variants and transitional forms are distinguished, their characteristics are presented. PMID- 7771926 TI - [Solitary eosinophilic granuloma of bone]. AB - Clinico-anatomical and pathomorphological analysis is carried out in 80 cases of SEBG that were treated or consulted in the Institute during 1963-1993. The following stages of SEBG are distinguished: 1--accumulation and proliferation of histiocytes; 2--granulomatosis; 3--regression. Obviously all SEBG which regress spontaneously or by means of punctures with intrafocal administration of medical drugs pass through these stages. Distinguishing these stages is of practical significance as well for the differential diagnosis and prognosis. When granulomatous process is persistent, Langerhans cells having little proliferative potencies and apparently releasing biologically active substances, are able to stimulate the formation of their precursors in the marrow and thus of supporting the pathological focus. PMID- 7771927 TI - [Tumors of the tracheal and bronchial glands]. PMID- 7771928 TI - [Osteochondroplastic tracheobronchopathy]. AB - 14 cases of osteochondroplastic tracheobronchopathy (OT) are studied histologically. The disease is characterized by formation of cartilage and bone tissue in the submucosa of the trachea and bronchi outside their own cartilagenous carcass. Its histogenesis is not clear and is attributed to chronic bronchitis, specific inflammation, dysembryogenetic alterations, endocrine disorders, environmental and occupational hazards, amyloidosis of the trachea. The process is localized in the trachea and bronchi as an isolated and rarely as a diffuse lesion. Morphologically, normal or atrophic mucous membrane is observed, at some places with a squamous metaplasia. Areas of cartilage with calcium deposits and foci of bone having a trabecular structure with formation of spongious bone tissue, sometimes with bone marrow, were found. PMID- 7771929 TI - [An immunohistochemical study of pepsinogen type C in the gastric mucosa and in stomach cancer]. AB - 129 cases of non-malignant gastric lesions and 171 cases of gastric carcinoma were studied immunohistochemically for pepsinogen C. PgC was constantly expressed at the bottom of the gastric glands irrespective of the disease. PgC was much more frequently observed in cancer patients (p < 0.001). PgC-positive were carcinoma tissues (38%), particularly of the intestinal type (53.4%), but also in mixed (40%) and diffuse (15.5%) types. PgC-negative carcinomas were more frequently observed in combination with PgC-positive areas of the surface epithelium (p < 0.001) and intestinal metaplasia (p < 0.05). PgC-positive dysplastic foci were observed in both groups of PgC-positive and PgC-negative malignant tumours. PMID- 7771930 TI - [Embryonal neuroepithelial tumors of the cerebral hemispheres]. AB - 33 embryonal neuroepithelial tumours of the cerebral hemispheres were examined light- and electron-microscopically, immunohistochemically. 4 types of tumours were distinguished: neuroblastoma, neuroepithelioma, ependymoblastoma and choroid carcinoma. Each type was characterised by its own pathohistological, immunohistochemical and ultrastructural features. Our results and literature data prove immunophenotypic and ultrastructural heterogeneity of embryonal neuroepithelial tumors of the cerebral hemispheres, in spite of some similarities in their pathohistological features. PMID- 7771931 TI - [The differential diagnosis of peripheral lung formations (cytological research)]. AB - The following pulmonary lesions were studied: carcinoma, carcinoid, tuberculoma, chondromatous hamartoma, chronic non-specific inflammatory process. Material was obtained through fiber bronchoscopy and roentgeno-endoscopical examination. Pappenheim staining in the modification of Astrakhantsev-Nechaeva and Ziehl Neelsen staining were used. 80 cases within 1993 were studied, among them 71 peripheral lung carcinomas. 3 carcinoids, 3 tuberculoses, 1 non-specific inflammation. Basic cytological criteria are summarized which will improve the quality of the presurgical diagnosis. PMID- 7771932 TI - [The functional morphology of the spleen and lymphoid apparatus of the intestines in stress]. AB - Structural and functional changes in the spleen and in the Payer plaques of the intestine under stress have been studied in 46 male rats. Stress activation of the adrenal cortex was blocked by metapiron injections. In cases of chronic stress along with the evident structural and functional damages in the immune system, in the spleen and in the peripheral blood there was a suppression of proliferative activity of T- and B-lymphocytes and an increase of functional activity of immuno-regulatory cells (T-suppressors). In chronic stress, specific compensatory changes due to the protective effect of metapiron preventing immunodepressive action of the adrenal gland hyperactivity were noted as well. PMID- 7771933 TI - [The age-related characteristics of the immune reaction of the mucosa of the gastric antrum in chronic gastritis]. AB - Stomach biopsies from 16 adult patients at the age from 18 to 55 years, 16 adults of 56-68 years and 23 children were studied histologically, immunohistochemically and morphometrically. The frequency of Helicobacter pylori findings was dependent on the age. Local production of IgM and IgG was higher in the adults of young and mature age. Number of IgA producing cells decreased and that of IgG producing cells sharply increased in the aged persons; in this category also was increased the number of intraepithelial lymphocytes and of T-lymphocytes relating to the subpopulation of suppressor cytotoxic cells. PMID- 7771935 TI - [Cerebral sarcoidosis diagnosed by biopsy]. AB - Space-occupying lesion was found by head computer tomography in the left brain hemisphere of the patients with lung and lymph node sarcoidosis. Neurologic symptoms and clinical course did not allow to exclude brain tumour. Granulomas typical for sarcoidosis were found in the stereotaxis biopsy of the parietal brain region. PMID- 7771934 TI - [The hyperinnervation phenomenon and the gradient distribution of nerve-growth factor activity in the tissue of the regenerating rat liver]. AB - An increase in the number and fluorescence intensity of liver nerve structures was recorded using fluorescent-histochemical method following 50% resection of the left lobe of the liver. Simultaneous isolation of liver NGF showed its activity in the operated lobe to have had gradient distribution, which motivated successful growth of nerve fibers to the zone of regeneration and development of hyperinnervation in it. PMID- 7771936 TI - [Chondrosarcoma of the lung]. AB - The description of this rare tumor in a male of 68 is reported. Clinical symptoms were hemoptysis, fever; was hospitalized with a suspicion of tuberculosis recurrence. Roentgenologically atelectasis of upper lobe of the right lung and obturation of the corresponding bronchus. Tumour had a diameter of 3 cm, histologically chondrosarcoma of the II degree of maturation with the inclusion of small cell sarcomatous areas (chondrosarcoma with a "mesenchymal" sarcomatous component). PMID- 7771938 TI - [Syringoma]. PMID- 7771937 TI - [Carcinoid of the kidney]. AB - Rare location of carcinoid tumour in the kidney is reported. The diagnosis was established on the basis of histological and ultrastructural investigation. PMID- 7771939 TI - [Vladimir Germanovich Shtefko--biologist, anatomist, anthropologist and pathologist (on the centenary of his birth)]. PMID- 7771941 TI - [The working out of the problems of tissue transplantation for the restoration of the locomotor organs by the school of T. P. Vinogradova]. PMID- 7771940 TI - [Prof. Tat'iana Pavlovna Vinogradova (on the centenary of her birth)]. PMID- 7771942 TI - [Lack of correlation between distension of papillary muscles and the magnitude of mitral valve prolapse]. PMID- 7771943 TI - [Early and delayed cardiac mortality after acute myocardial infarction in the pre thrombolytic era. Prognosis value of an ergometric test and coronary arteriography]. AB - PURPOSE: To determine the relationship among clinical data, attenuated treadmill stress test (ST), cinecoronaryarteriography (CINE), ejection fraction (EF) with early-late mortality in patients after acute myocardial infarction (AMI). METHODS: Prospective study in 96 consecutive patients aged < 70 with AMI that were submitted to ST and CINE. Assessment of cardiac mortality was made 1-3 years post-AMI (period I) and at the end of follow-up (7-10 years-period II). RESULTS: First year and 10th year mortalities were 8% and 36%, respectively. Positive predictive value for cardiac death in period I was 10% for ST, 7% for multivessel coronary artery disease (MVCAD) and 9% for left ventricular ejection fraction (LVEF) < 30, while in period II they were 45%, 42% and 50%, respectively. Actuarial survival analysis (Kaplan-Meyer) disclosed mortality rates of 53% and 20% (p = 0.06) on period II for positive and negative ST, respectively, 45% and 22% (p < 0.03) for MVCAD and single-vessel disease, respectively, and 73% and 35% (p < 0.001) for those with and without left main coronary artery obstruction, respectively. In the multivariate regression analysis (Cox's model), only MVCAD (p < 0.002), LVEF < 30 (p < 0.003), positive ST (p < 0.007) and post-AMI angina (p < 0.01) were independently related to late mortality. CONCLUSION: Both attenuated ST and CINE are poor predictors of post-AMI early and late mortalities. However, multivariate regression analysis disclosed positive ST, MVCAD and LVEF < 30 as independent variables related to late mortality. This data indicate that myocardial ischemia, number of obstructed coronary arteries and poor left ventricular systolic function are the true determinants of post infarction cardiac mortality. PMID- 7771944 TI - [Chronic phase of Chagas disease. Clinical aspects and course of the disease]. AB - PURPOSE: To evaluate the clinical and evolutive aspects of chronic chagasic patients. METHODS: Three hundred chronic chagasic patients, 180 females, with age ranging from 19 to 81 years (55.6 +/- 13.1) were retrospectively studied. Patients were divided according to the following clinical types: indeterminated, cardiac (with the subtypes: arrhythmogenic, dilated and mixed), digestive isolated and digestive plus cardiac involvement. The following variables were analysed: prevalence of each clinical forms, symptoms, electrocardiographic pattern and clinical outcome. RESULTS: At the start of the study, 73 (24.3%) patients were in indetermined type, 106 (35.3%) in cardiac arrhythmogenic, 95 (31.6%) in mixed, 7 (2.3%) in dilated, 16 (5.3%) in digestive plus cardiac type and 3 (1%) in the pure digestive type. The most prevalent symptoms were dyspnea on efforts (57%), palpitations (41.33%) and chest pain (33%). The most frequent electrocardiographic pattern was right bundle branch block plus antero-superior fascicular block, in 30% of the patients. The average follow-up time was 7.8 +/- 6.1 years and the outcome was considered good in 20 patients (6.6%), stable in 214 (71.3%) and bad in 66 (23%). At the end of the follow-up, 9 patients have evaluated from the indeterminated to the cardiac and digestive types, and 19 (17.92%), from the arrhythmogenic to mixed cardiac subtype. The follow-up was lost in 79 patients (26.3%), most of them, probably dead. CONCLUSION: With a mean time of 7.8 years, 12.3% of the patients in the indeterminated type evolved to the cardiac and/or digestive type; right brundle branch block with antero superior fascicular block was the most prevalent electrocardiographic pattern; the outcome was stable or good in the majority of these patients. PMID- 7771945 TI - [Initial heart rate transient at dynamic exercise performed in apnea. Influence of the variation rate of previous lung volume]. AB - PURPOSE: To study the influence of inspiratory flow on the heart rate (HR) responses during the four-second exercise test (4sET) as a method to estimate cardiac vagal activity. METHODS: Fifteen healthy subjects performed the 4sET under two experimental situations: a) with maximal individual inspiratory flow (MIF) and b) with a slow inspiratory flow adjusted to reach total lung capacity in 4s (SIF). Vagal activity was estimated from B/C ratio obtained in ECG tracings, where B is the last R-R interval before the onset of exercise and C is the shortest R-R interval during exertion. RESULTS: Similar inspiratory capacities were reached, with significantly different inspiratory flows [mean (se)] [MIF = 2.23 (0.28) 1.s-1 and SIF = 0.59 (0.06) 1.s-1; t = 6.69; p < 0.0001]; as a result, it was observed a greater B/C ratio in MIF [1.36 (0.05)] as compared to SIF [1.13 (0.04); t = 4.42; p = 0.0006]. The inspiratory flow influenced HR responses in the 4sET. The biphasic transient induced by inspiration, with a HR acceleration followed by a relative bradycardia, has not been completed before exercise in the 4sET with SIF. CONCLUSION: Lower values of B/C in the 4sET with SIF seemed to be due to overlapping effects of apnea and exertion on HR during cycling. On the other hand, when the inspiration was performed at MIF, the oscillatory effect of respiration upon HR was completed before the onset of exercise. Therefore, the tachycardia observed during the 4sET performed after individual maximal inspiratory flow represents the isolated effect of dynamic exercise. PMID- 7771946 TI - [Emergency valvuloplasty with a balloon catheter of a tricuspid bioprosthesis in Ebstein's anomaly]. AB - A case of severe stenosis of a tricuspid bioprosthesis was successfully dilated in a 13 year old young male with Ebstein's anomaly. The patient had congestive heart failure and developed cardiogenic shock; angiography revealed absence of emptying of the right atrium. Multiple size balloons (#4 to 23) were sequentially introduced with successful bioprosthesis dilation and shock resolution. Tricuspid bioprosthesis can be dilated even in critical conditions and, although a palliative procedure, balloon valvuloplasty can be a lifesaving procedure in patients with cardiogenic shock. PMID- 7771947 TI - [Use of sympathomimetic agents in fetal atrioventricular heart block]. AB - A healthy pregnant was referred at 34 weeks gestation because an obstetrical ultrasound examination had shown fetal bradycardia and nonimmune hydrops. The heart was anatomically normal but complete heart block was present with a ventricular rate of 22bpm and atrial of 101bpm. We injected isoproterenol by cordocentesis direct in the umbilical vein of the fetus and a significant increase into the ventricular and atrial rates were obtained. The direct therapy with sympathomimetic drugs is a simple technique and may save fetuses with complete heart block and hidrops. PMID- 7771948 TI - [Prolonged respiratory support with extracorporeal membrane oxygenation in lung transplantation]. AB - A 42 year-old woman with terminal chronic lung disease underwent to left lung transplantation. Extracorporeal membrane oxigenation (ECMO) was required because dysfunction of transplanted organ occurred and was non-responsive to conventional therapy. The time of assistance was 47 hours and after this, the dysfunction of the transplanted lung reversed and the patient was weaned from the oxigenator. During hospital stay, she developed sepsis and died. In conclusion, ECMO was decisive to the treatment of pulmonary dysfunction, allowing time to the resolution of lung lesion. PMID- 7771949 TI - [Aneurysms of the left and non coronary sinus of Valsalva associated to mitral and aortic rheumatic valves and obstructive coronary disease]. AB - A 30 years old, male, patient with rare multiple aneurysms of sinus of Valsalva associated to mitral and aortic regurgitation and total occlusion of circumflex artery had the clinical diagnosis made accidentally. The multiple aneurysms were detected by transesophageal echodopplercardiography and hemodynamic study. The diagnosis were confirmed at surgery and the patient underwent correction of the aneurysms through the use of pericardial patches and mitral and aortic valve replacement. PMID- 7771950 TI - [Chronic high levels of CK-MB]. AB - We presented two cases of falsely elevated CK-MB due to the presence of a type 2 macro CK, showed by isoenzymes electrophoresis. The association of this CK-MB falsely elevated with some digestive diseases are frequent. Quantification of CK isoenzymes by electrophoresis could be indicated in those cases in which the clinical course or ECG changes do not correlate with the CK-MB values. PMID- 7771951 TI - [Treatment of orthostatic hypotension with metoclopramide]. AB - A 38 year-old woman, with orthostatic hypotension secondary to autonomic dysfunction accompanied by sympathetic hyperactivity and excess of dopamine, was treated with an antagonistic dopaminergic drug, metoclopramide, 30 mg/day, with good tolerance. Support intervention as well as the use of various drugs (beta blockers, caffeine, fludrocortisone, haloperidol) showed no effect. The answer to metoclopramide both subjective and objective were remarkable. The way in which metoclopramide acts has not yet been fully clarified. Being a widely used drug, well tolerated, its use must be considered in cases of severe orthostatic hypotension, especially those with an excess of dopamine. PMID- 7771952 TI - [Rheumatic fever. Advances in the study of its pathogenesis in the most recent decades]. PMID- 7771953 TI - [Evaluation of the therapeutic efficacy of delayed-action diltiazem in the treatment of mild and moderate hypertension, with ambulatory of blood pressure monitoring]. AB - PURPOSE: To evaluate the behaviour of 24 hour blood pressure and the therapeutic efficacy of diltiazem 240mg (slow release) in mild and moderate hypertension. METHODS: In an open noncomparative study 20 hypertensive patients were evaluated after two weeks of wash out and eight weeks of therapy. Diltiazem 240mg, slow release, was used in once a day basis. The blood pressure was evaluated through casual measures and by ambulatorial (ABPM) blood pressure monitorization. RESULTS: Sixteen patients (80%) reached therapeutic success (PAD nomalization or at least a reduction of 10mmHg), after six weeks of therapy. There were no changes in heart rate nor orthostatic hypotension. The mean reduction for the systolic blood pressure (PAS) was the 19.25mmHg and for PAD 11.60mmHg. The variables identified in ABPM (systolic and dyastolic load, SBP and DBP) showed significant reduction with maintenance of the circadian rhythm. CONCLUSION: Diltiazem 240mg, slow release, showed significant reduction (therapeutic success = 80%) in blood pressure of mild and moderate hypertensive patients associated with excellent tolerability. The circadian rhythm has been kept. The variables measured by ABPM were significantly reduced. Diltiazem demonstrated to be an important alternative for the treatment of mild to moderate hypertension due to its beneficial therapeutic effects associated to the once daily dosage. PMID- 7771955 TI - [Second Brazilian consensus on the treatment of arterial hypertension]. PMID- 7771954 TI - [Randomized, double-blind comparative study between pravastatin and lovastatin. Evaluation of efficacy and safety]. AB - PURPOSE: To verify eventual difference observed in the efficacy and safety of lovastatin (L) when compared to pravastatin (P), considering increasing doses up to the maximum and recommended ones in clinical practice. METHODS: Forty-eight hypercholesterolemic patients (LDL-C > 160 mg/dl after a placebo seven-day period) were studied and randomly assigned to constitute groups of 24 patients (GL and GP groups). The patients from GL group received L 20 mg/day and those from GP group P 10 mg/day, in a double-blind fashion. Six and 12 weeks later, the those were doubled. At the end of the placebo period and at weeks 6, 12 and 18 they were evaluated for clinical data and laboratorial parameters, such as: lipid profile (TC, TG, HDL-C and LDL-C); enzymes AST, ALT, CPK, gamma-GT, alkalin phosphatase); biochemical data (urea, creatinine, bilirubin, uric acid, glucose); complete blood count and urinalysis. RESULTS: Both drugs have shown significant reductions in TC and LDL-C levels at the lowest clinical doses (L 20 mg/day; P 10 mg/day), which became more marked as doses were gradually increased. However, the responses were always significantly greater for L in all doses employed. No adverse effects requiring treatment discontinuation were observed for both drugs. CONCLUSION: L showed a higher TC and LDL-C lowering effect than that observed with P, when the doses recommended by the respective manufacturers were compared. PMID- 7771956 TI - Trusting trials: can science help improve pharmaceutical health for all? PMID- 7771957 TI - A diabetes practice assessment activity--Part 3. PMID- 7771958 TI - An overview of medical imaging in the Roentgen centenary year. AB - This article reviews briefly current opinion regarding optimal imaging in a number of clinical situations presenting in family practice. The choice of imaging procedure, of course, depends upon availability, particularly in country areas. Nuclear medicine especially has not yet become as widely disseminated outside the large cities. To exclude repetition, topics that are the subject of more extensive review later in this issue have been excluded from this article. PMID- 7771959 TI - Cost versus efficacy of magnetic resonance imaging. AB - Magnetic resonance imaging offers new and improved diagnostic capabilities in all body parts and organ systems. Examinations can be quicker, safer and less expensive than traditional radiological procedures. The cost/efficiency of magnetic resonance imaging is under active evaluation. PMID- 7771960 TI - Aspects of musculoskeletal magnetic resonance imaging. AB - MRI can clearly identify many pathological processes in the musculoskeletal system. Because it is a non invasive investigation, it plays an important role in assessing joint pathology and musculoskeletal masses prior to any interventional procedure. If used properly, it can be cost effective and redundant diagnostic tests can be reduced, appropriate therapy can be instituted and unnecessary surgical intervention and hospitalisation can be avoided. PMID- 7771961 TI - Prostatic imaging: the role of transrectal ultrasound. AB - Until a few years ago, there was no acceptable imaging modality available for the prostate gland. Since the high frequency endo-rectal ultrasound transducers have been developed, transrectal ultrasound (TRUS) has gained wide acceptance as the method of choice for imaging assessment of common prostate conditions including prostate carcinoma. PMID- 7771962 TI - Musculoskeletal and small parts ultrasound. AB - Since the mid 1980s there has been a marked improvement in the technical quality of high frequency ultrasound probes for small part imaging Many superficial organs are ideally suited for ultrasound examination. The addition of colour doppler facilities has further enhanced ultrasounds' diagnostic capabilities particularly with scrotal ultrasound. PMID- 7771963 TI - Radiology and low back pain. AB - An outline of radiological investigations for patients with low back pain is presented. The article emphasises the need for thorough clinical evaluation of patients before any radiological investigations are undertaken. The types of radiological tests best suited to particular clinical problems are highlighted. PMID- 7771964 TI - Abdominal ultrasound. An overview for general practitioners. AB - The authors review some of the commoner indications and pathologies encountered in the context of general practice in which ultrasound has a role. Gynaecological indications and paediatric ultrasound will not be discussed. PMID- 7771965 TI - What's new in pulmonary radiology? AB - Research is still continuing to produce the ideal radiographic emulsion and the film plate will be in use for some time yet. Digital imaging will develop, but there are problems to overcome. Computerised tomography (CT) continues to improve despite early predictions to the contrary, and magnetic resonance imaging (MRI) will make an impact, especially with MRI angiography and fast-gated scanning techniques. PMID- 7771966 TI - The management of work caused lumbosacral injury. Development and content of professionally agreed guidelines. AB - A guidelines committee representing 20 professional organisations involved in the management of work related lumbo-sacral injury was convened in South Australia to formulate a consensus plan of management for this complex problem. This paper outlines the development and the content of the agreed guidelines. PMID- 7771968 TI - General practice medical records: why code? Why classify? AB - Recently, the Information Management Steering Group (IMSG) [a RACGP-AMA Commonwealth Government committee responsible for the planning of information management in general practice], held a Coding Workshop at which available coding systems and their application in general practice computerised medical records were reviewed. As there has been in the past some discussion as to the value of coding, the workshop participants agreed that a paper outlining the reasons for coding and classifying clinical data should be prepared and disseminated to all general practitioners. PMID- 7771967 TI - Assessing work capacity. Implications for medical practitioners. AB - Work capacity assessments have become an important area of clinical practice. The authors discuss some key concepts and common problems when conducting such assessments. PMID- 7771969 TI - Conolly Oration. The skilled doctor: in defence of the pursuit of excellence. PMID- 7771970 TI - Incidence patterns of respiratory illness in Queensland estimated from sentinel general practice. AB - Incidence rates of six respiratory infections were calculated from sentinel practice data of 33,407 reports coming from 31 general practitioners in Queensland over 34 months in 1986/1988. Upper respiratory tract infection had an annual incidence of 301 per 1000 people, most in children aged under five, and a winter rate twice the summer rate. Sore throat (incidence 112:1000) and Infectious mononucleosis (incidence 2.7:1000) had little seasonal variation and were maximal among those aged 15-19 (in whom there was one case of Infectious mononucleosis for every 14 sore throats). Influenza (incidence 44:1000) underwent a prominent epidemic in the winter of 1988. Measles (incidence 1.9:1000), and pertussis and pertussis-like syndrome (incidence 0.8:1000) were most commonly reported in the under-fives, and rarely among adults. Sentinel practices networks collect useful epidemiological data from which disease incidences can be calculated. PMID- 7771971 TI - Helen Mary Caldicott. Doctor to the planet. AB - A very strong sense of vocation to become a doctor since the age of eleven led Helen Caldicott into her profession of healing. This passion to heal has become global in the sense that Helen sees the earth as a living organism requiring the fundamentals of caring-preventive care, continuing care and fighting chronic 'illness'. General practitioners who were present at her keynote opening address at WONCA in Vancouver 1992, marvelled at the powerful and logical impact of her presentation about the preservation of our earth. PMID- 7771972 TI - Critical assessment of ACE inhibitors. Part 2. AB - Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, and pharmacodynamics between the various ACE inhibitors generally do not translate into significant clinical differences in the majority of patients. However, fosinopril may be the preferred ACE inhibitor in patients with significant renal dysfunction because of a reduced requirement for dosage reduction. The duration of action of ACE inhibitors is determined by two properties, the plasma half-life and the affinity of binding to tissue ACE. All of the ACE inhibitors (with the possible exception of captopril) can provide satisfactory 24-hour blood pressure control in the majority of patients with mild to moderate hypertension when given once daily. Lisinopril provides consistently better 24-hour control of blood pressure than either captopril or enalapril. Evidence for superior 24-hour blood pressure control over enalapril has not been as well established for the other ACE inhibitors. Captopril may be preferred for initiating therapy in patients with severe heart failure who are at risk of first dose hypertension because of its rapid onset of action and relatively short duration of action. There is evidence, however, that perindopril may have a low risk of first dose hypertension in heart failure because of its gradual onset of action. Long-acting ACE inhibitors may be preferable for chronic therapy of heart failure. All of the ACE inhibitors have a low incidence of adverse effects in both young and elderly patients, and there is no convincing evidence of differences in tolerability between the drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771973 TI - Common facial skin disorders. PMID- 7771974 TI - Patient education. Halitosis. PMID- 7771975 TI - Tarsal tunnel syndrome. PMID- 7771976 TI - Ode to mortality. PMID- 7771977 TI - Chronic diarrhoea with relapse after treatment. PMID- 7771978 TI - Accident and emergency medicine. Acute dyspnoea. PMID- 7771979 TI - Removal of embedded fish-hook. PMID- 7771980 TI - 'Supermarket' v 'boutique' general practices. PMID- 7771981 TI - CARE Germany in Zaire: a clarification. PMID- 7771982 TI - Working in Zaire. PMID- 7771983 TI - Major fetal malformations and perinatal mortality rates: the place of late terminations. PMID- 7771984 TI - Successful pregnancy in the DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, deafness). AB - A case of successful pregnancy in a patient with the complete DIDMOAD syndrome is described. Attention is drawn to the need to monitor fluid balance carefully during and after pregnancy in this condition. The current literature in the area is reviewed. PMID- 7771985 TI - Neonatal infection due to Haemophilus influenzae biotype IV. AB - Neonatal infection due to Haemophilus influenzae has several clinical similarities to infection by the more common Streptococcus agalactiae (Strep group B). A high frequency of H. influenzae biotype IV in association with genital, maternal and neonatal infections has been reported in the literature, suggesting this biotype has an affinity for the female genital tract. Cefotaxime should be considered as part of the treatment regimen when this organism is suspected because of the emerging resistance of H. influenzae to ampicillin. We present a case of H. influenzae biotype IV infection in a premature (32 weeks) neonate. PMID- 7771986 TI - Ogilvie syndrome with caecal perforation in the post-caesarean patient. PMID- 7771987 TI - Insertion of a permanent electrode for intractable detrusor instability. PMID- 7771988 TI - Goserelin reduction of uterine fibroids prior to vaginal hysterectomy. PMID- 7771989 TI - Early severe haemorrhage complicating GnRH analogue treatment of submucous uterine fibroids. PMID- 7771990 TI - Falloposcopy can be useful. PMID- 7771991 TI - Nulliparous caesarean section in the home of active management of labour. AB - The world-wide incidence of Caesarean section continues to rise with dystocia recognized as the major indication. Active management of labour has been proposed as an alternative treatment to Caesarean section for dystocia. At the National Maternity Hospital, Dublin, a recent increase in the Caesarean section rate has been observed. This retrospective review reveals this to be due to other indications. PMID- 7771992 TI - Severe twin-twin transfusion syndrome: current management concepts. AB - The presence of functioning vascular anastomoses within the monochorionic placentation of a monozygotic twin pregnancy is responsible for the twin-twin transfusion syndrome. This is a heterogeneous disorder with a wide spectrum of severity. In the most severe form it results in the oligohydramnios polyhydramnios sequence with a marked disparity in intertwin biometry and amniotic fluid volume. Without therapy, the perinatal mortality of severe twin twin transfusion syndrome is 60-100%. Several therapeutic interventions have been attempted with therapeutic amniocentesis producing the most consistent improvement in fetal survival rates. The outcome of 10 cases of severe twin-twin transfusion syndrome, presenting as the oligohydramnios-polyhydramnios sequence, is presented. Gestational age at presentation ranged from 20-34 weeks. Three fetuses were hydropic at initial presentation and of these only 1 survived. All cases were treated with serial aggressive therapeutic amniocentesis, the number of procedures ranging from 1-9/patient. The volume of amniotic fluid removed ranged from 3,200-14,000 mL. Gestation was prolonged a mean of 46 days (range 1 106 days). The perinatal survival rate was 65% (13/20 infants). Preterm premature rupture of membranes and secondary preterm birth complicated 1 pregnancy treated with therapeutic amniocentesis. Short-term morbidity in the liveborn infants was predominantly secondary to prematurity and renal cortical necrosis. Severe twin twin transfusion syndrome is the most common aetiology of the oligohydramnios polyhydramnios sequence. Therapeutic amniocentesis offers an intervention that may reduce the high perinatal loss rate previously observed with this disorder. PMID- 7771993 TI - Twin-twin transfusion syndrome: intraamniotic pressure measurement in the assessment of volume reduction at serial amniocenteses. AB - Two cases of severe twin-twin transfusion syndrome are described. In both, serial amniocenteses were followed by resolution of the disordered inter-twin haemodynamics with 4 intact term survivors. In all reports to date of aggressive reduction with or without successful outcome, volume reduction has been dictated by subjective or semiquantitative ultrasonic estimates of liquor volume. With the use of intraamniotic pressure estimation we describe a more rational basis for the removal of these large volumes of amniotic fluid. PMID- 7771994 TI - Singleton and twin confinements associated with infertility treatments. AB - A cross-sectional sample of 150 singleton and 159 twin confinements delivered in Western Australia in 1991 were randomly sampled in 1993; 63% of the women responded to a postal questionnaire. Thirteen percent of respondents with singletons and 26% of those with twins reported having problems conceiving at some stage in their life. Six percent of those who had singleton confinements and 22% of those women who had twin confinements sought fertility advice prior to the conception of the index pregnancy. One percent (95% CI 0.03%, 5.5%) of women with singletons received infertility treatment compared with 17% (95% CI 10.4%, 26.3%) of those with twins. Overall 82.7% (95% CI 75.2%, 90.1%) of twin confinements followed spontaneous conception, 11.2% (95% CI 5.7%, 19.2%) followed ovarian stimulation treatment alone and 6.1% (95% CI 2.3%, 12.9%) followed IVF or GIFT procedures. The probability of a spontaneous twin confinement was 1 in 95. It was concluded that nearly twice as many twin pregnancies were associated with ovarian stimulation treatment given alone than with IVF and GIFT combined. The routinely collected data about assisted twin conceptions provide an incomplete picture with regard to the role of different infertility treatment modalities. PMID- 7771996 TI - Measurements of blood pressure, oedema and proteinuria in a pregnant population of New Zealand. AB - This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that blood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Hg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of > 33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7771995 TI - Prenatal diagnosis and late termination: a legal perspective. AB - The purpose of prenatal screening is obviously to identify genetic and other disorders before a child is born. In the majority of cases, the intention is that the pregnancy should be terminated if the child is found to be affected by a serious disorder. Despite this expectation, the law in Victoria does not recognize fetal abnormality as a ground for abortion. For an abortion to be lawful, the doctor must honestly believe, on reasonable grounds, that the abortion is 'necessary to preserve the woman from a serious danger to her life or her physical or mental health' and that the abortion is 'not out of proportion to the danger to be averted' (the Menhennitt rules). Although the danger to health has been extended to include danger on economic and social grounds, it is still necessary for a doctor to base the decision to abort on the risk to the mother's health, and not on the abnormal fetus. When the fetus is older, a doctor may be charged with child destruction as well as abortion. This requires proof that the doctor 'unlawfully cause[d] such child to die' and acted 'with intent to destroy the life of a child capable of being born alive'. These terms are open to interpretation but it is not necessarily a defence that the child had a serious abnormality. PMID- 7771997 TI - Aspirin and prevention of preeclampsia. Position statement of the use of low-dose aspirin in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy. AB - 1. A heterogeneous group of randomized trials have been conducted using low-dose aspirin to prevent preeclampsia. The results do not support widespread use of low dose aspirin to prevent preeclampsia. 2. On the basis of existing literature, it is reasonable to use prophylactic low-dose aspirin from early pregnancy in the following groups: (i) Women with prior fetal loss after the first trimester, with placental insufficiency (ii) Women with severe fetal growth retardation in a preceding pregnancy either due to preeclampsia or unexplained (iii) Women with severe early-onset preeclampsia in a previous pregnancy necessitating delivery at or before 32 weeks' gestation. 3. On the basis of existing literature, it is recommended that aspirin not be used in the following groups: (i) Healthy nulliparous women (ii) Women with mild chronic hypertension (iii) Women with established preeclampsia. 4. The data are sufficient to support further trials in more homogeneous select subgroups of women considered at risk of developing preeclampsia. PMID- 7771998 TI - The role of transvaginal sonography in the diagnosis of placenta praevia. AB - Transvaginal sonography was performed in 70 patients diagnosed to have placenta praevia by transabdominal sonography. The diagnosis was confirmed either by digital examination in theatre at term or operative finding at delivery. Forty nine cases (70%) were correctly diagnosed to have placenta praevia by both modes of sonography. Transvaginal sonography ruled out placenta praevia in 12 cases (17%) thought to be placenta praevia by transabdominal ultrasound. Both transabdominal and transvaginal sonography demonstrated 'placental migration' in 4 cases (6%) which were no longer praevia at delivery. Five patients (7%) were erroneously believed to have placenta praevia by both sonographic techniques. Overall, the diagnostic accuracy of transvaginal sonography was 92.8% compared with 75.7% for transabdominal sonography. None of the subjects experienced any exacerbation of bleeding or other complications. The results suggest that transvaginal sonographic localization of the placenta is safe and superior to the transabdominal route. PMID- 7771999 TI - The effect of vigorous exercise during pregnancy on birth-weight. AB - The aim of this study was to assess the effect on birth-weight of continuing a programme of vigorous exercise into late pregnancy. 'Potential exercisers' were women who had been doing vigorous exercise prior to pregnancy and intended to continue exercising during pregnancy. Controls were healthy pregnant women who did not do regular vigorous exercise. Both groups kept 2, 7-day food +/- exercise diaries at 25 and 35 weeks. The primary outcome variable was birth-weight. Women who continued doing at least 30 minutes of vigorous exercise at least 3 times weekly at 25 weeks and either maintained this minimum level or had delivered by 35 weeks were classified as 'exercisers'. Women doing more than 4 sessions of vigorous exercise weekly at 25 weeks had babies whose mean birth-weight was 315 g lower than the mean birth-weight of babies born to controls. PMID- 7772000 TI - The feasibility of early second trimester pregnancy (12 to 14 weeks) termination with single intra-amniotic injection of 15-methyl PGF2 alpha. AB - Prostaglandin analogues have proven to be safe and effective for second trimester pregnancy terminations when given by various routes. Of these, the intra-amniotic (IA) route has proven to be safer, especially in women with medical disorders, as it causes the least occurrence of systemic side-effects. Previously, blind transabdominal IA instillation of the analogue 15-methyl PGF2 alpha was routinely possible only after 16 weeks' gestation. With the advent of ultrasound-guided techniques, it has now become possible to use the IA route for very early second trimester pregnancies. This study examines the use of single 1.5 mg 15-methyl PGF2 alpha IA injection for termination of 12-14 weeks pregnancies. Single injection resulted in successful abortion in 76.5% of women and, in the unsuccessful cases, additional prostaglandin injection resulted in successful abortion in all women within 48 hours without problems. It is therefore feasible to use ultrasound-guided IA prostaglandin injection for successful termination of early second trimester pregnancies. PMID- 7772001 TI - Intravaginal misoprostol for termination of midtrimester pregnancy. AB - Misoprostol seems to be a drug with many potential uses apart from the treatment of gastric and duodenal ulcers. The oral tablet appears to be effective for termination of midtrimester pregnancy when administered intravaginally. Further research should be carried out to determine its full range of action in order that the drug can be utilized to its maximum potential. PMID- 7772002 TI - Vaginal and speculum examination in medical curricula. AB - Medical students' perception of their own psychomotor skills and attitudes to different methods of teaching the gynaecological examination were studied. Students rated their physical skills poorly, only 7% feeling confident they could detect an abnormality and only 14% considering their ability to perform a Pap smear was good or very good. They rated their doctor/patient skills better, 55% considering they are good at conducting an examination with sensitivity and 67% at explaining to their patient what they were doing and why. Students' first preference for instruction was to examine patients in the Outpatient Clinic under the supervision of a doctor, a method experienced by most students on one occasion. The next preferred method was for students to work with 2 trained gynaecological assistants, acting as patient and instructor, with discussion of feelings and feedback (see Subjects and Methods). The option of student volunteers was a least favoured method but was cited as first preference by 5% of students. Over 25% of the female students considered volunteering for vaginal examination a 'possibility' if they were examined by a student of the same sex. Over 25% of males would 'possibly' volunteer for rectal examination only if the same sex was present. The comments by the students offer help in the future planning of teaching vaginal examination. PMID- 7772003 TI - Variation in caesarean and instrumental delivery rates in New Zealand hospitals. AB - A study of Caesarean section and instrumental delivery rates in the maternity hospitals in New Zealand delivering over 1,000 women per year was undertaken. The results at Middlemore Hospital were compared with those seen elsewhere. The Caesarean section rate at Middlemore Hospital in 1993 was significantly lower than the other large maternity hospitals in New Zealand. The Caesarean section rate at Middlemore from 1988 to 1993 has shown a significant downward trend which is different from the trends at other hospitals. The spontaneous vaginal delivery rates at Middlemore Hospital were higher than at other New Zealand hospitals between 1988 and 1993. We conclude that Middlemore Hospital has been successful in maintaining low interventional delivery rates by New Zealand and international standards--the Caesarean section rate remains below 10% and the spontaneous vaginal delivery rate approaches 85%. This is likely to be a consequence of a number of factors operating together but there is evidence to suggest that obstetric management policies at Middlemore do play a role in this. PMID- 7772004 TI - Education and hysterectomy. AB - A small Canberra survey provided the opportunity to investigate the observation that tertiary education is associated with lower hysterectomy rates. Despite the sample's being small and unrepresentative of either the Australian or even the Canberra population, it was possible to replicate a simple version of a national model of hysterectomy. Tertiary education remained strongly predictive of a low rate of hysterectomy. Additionally, the study showed, first, the tertiary educated women were less likely than others to be told that they needed a hysterectomy in the first place. Secondly, they were less likely to accept such advice: hysterectomy was undergone by only 1 of 5 of the better educated women to whom it had been suggested, but by 4 of 5 of the less educated. PMID- 7772005 TI - Vulvar cancer. PMID- 7772006 TI - Vulvar cancer: the Cinderella of gynaecological oncology. AB - Cancer of the vulva is a rare malignancy that increases progressively with age. The age-standardized incidence averages between 1 and 2 per 100,000 women in Western countries. The majority (80-90%) are squamous cell carcinomas, melanoma and adenocarcinoma each accounting for about 5% of cases. Internationally, the incidence of vulvar cancer varies more than 30-fold, the highest rates being seen in populations of Portuguese South America. In many populations the incidence appears to be stable but there is some evidence that the incidence of in situ carcinoma is increasing in the United States of America. Epidemiological studies have identified sexual factors, particularly human papilloma virus (HPV) infection, as increasing risk. Smoking also increases risk by interacting synergistically with HPV infection and genital warts. The aetiologies of vulvar intraepithelial neoplasia (VIN)3/in situ disease and invasive cancer appear to differ. VIN does not automatically progress to invasive cancer and is strongly associated with HPV infection. Many older women with invasive vulvar cancer do not have evidence of HPV and do not smoke. More research is needed on the cause of vulvar carcinoma in this group. Treatment has become more conservative over the years and this has reduced morbidity and probably mortality. Although FIGO data do not show much by way of improvement in survival, data from population based cancer registries have shown definite increases in survival (5-year survival proportions in excess of 80%, when age and Stage have been taken into account). Improvement is particularly related to the preponderance of early stage disease. PMID- 7772007 TI - Endoscopic minilaparotomy. AB - In a preliminary study the principles of standard gynaecological surgery, new operative laparoscopic techniques and mechanical elevation of the abdominal wall are combined. These early results indicate an advantage to both patient and hospitals from this approach. Further studies are required to verify our impressions that minilaparotomy combined with no insufflation laparoendoscopy will open up the concept of operative laparoscopic surgery to most gynaecologists. PMID- 7772008 TI - Laparoscopically-assisted vaginal hysterectomy. AB - A series of 153 consecutive patients is presented in whom a laparoscopically assisted vaginal hysterectomy was planned and was performed in 147 of them (96%). Bipolar diathermy was utilized to diathermy the upper uterine pedicles above the uterine arteries. Neither the uterine arteries nor the uterosacral ligaments were ligated laparoscopically and the remainder of the hysterectomy was performed vaginally. In the other 6 patients in whom the operation was commenced laparoscopically, it was discontinued and the operation concluded vaginally in 1 patient and abdominally in the other 5 patients. The aim of using the laparoscopic technique has been to convert a potential abdominal hysterectomy into a vaginal hysterectomy. The technique and the results are discussed. PMID- 7772009 TI - Female circumcision. AB - Three cases of female circumcision are presented together with a literature review. Unfortunately, this procedure frequently results in genital mutilation. Treatment with deinfibulation enables restoration of the external genitalia and vagina. Obstetric and gynaecological complications have been documented, but emotional and psychological effects may be difficult to assess. These women should be treated without bias and with sensitivity. PMID- 7772010 TI - Sacrospinous colpopexy. AB - Sacrospinous colpopexy is a useful procedure in the cure of pulsion enterocele, high rectocele, and posthysterectomy vault prolapse. It allows the surgeon to correct coincident cystocele and rectocele and permits restoration of a relatively normal and comfortable vaginal depth and axis. It is a quick procedure, avoids intraabdominal trauma, has a high success rate and a low complication rate (1) and is useful in the management of patients who wish to maintain coital function. This paper retrospectively reviews the techniques, results and complications of 107 sacrospinous colpopexies performed in 104 patients over an 8-year interval. PMID- 7772011 TI - Spontaneous uterine perforation as a serious complication of pyometra in elderly females. PMID- 7772012 TI - Continuous combined piperazine oestrone sulphate and medroxyprogesterone acetate hormone replacement therapy--a study of bleeding pattern, endometrial response, serum lipid and bone density changes. AB - This pilot study was conducted to establish the optimum oral dosage of medroxyprogesterone acetate (Provera) given daily in combination with a fixed dose of piperazine oestrone sulphate (Ogen), as hormone replacement therapy. A group of 32 nonhysterectomized, symptomatic menopausal women were randomly allocated to receive piperazine oestrone sulphate 1.25 mg daily and medroxyprogesterone acetate 2.5 mg, 5 mg or 10 mg daily for a 2-year period. This was an open study and the patients were reviewed at 3-monthly intervals for 2 years. Vaginal bleeding was reported by 58% of patients after the first 3 months of treatment. There was a gradual decline in the reported incidence of bleeding over the following 6 months particularly by women in the 5 mg and 10 mg Provera group. Only 10% of patients were still recording slight bleeding in the 10 mg group at 12 months. By 24 months all the women in the 5 mg and 10 mg Provera groups had ceased bleeding. There were 2 patients in the 2.5 mg Provera group with persistent proliferative endometrium at 24 months. All the remaining patients had atrophic endometrium. There was no significant difference in serum lipid changes between the 3 groups, but there was an overall reduction in total cholesterol, triglycerides and low density lipoprotein cholesterol in all women. There was no significant difference in bone mineral density changes between the groups over the 2-year period. Endometrial protection with increased incidence of amenorrhoea, without significant adverse effects, was seen with the use of 5 mg and 10 mg of provera. PMID- 7772013 TI - First trimester antigen typing of fetal red cells using a flow cytometric technique. PMID- 7772014 TI - Falciparum malaria in pregnancy. PMID- 7772016 TI - The structure of the quinoprotein alcohol dehydrogenase of Acetobacter aceti modelled on that of methanol dehydrogenase from Methylobacterium extorquens. AB - The 1.94 A structure of methanol dehydrogenase has been used to provide a model structure for part of a membrane quinohaemoprotein alcohol dehydrogenase. The basic superbarrel structure and the active-site region are retained, indicating essentially similar mechanisms of action, but there are considerable differences in the external loops, particularly those involved in formation of the shallow funnel leading to the active site. PMID- 7772018 TI - Effect of intracellular iron depletion by picolinic acid on expression of the lactoferrin receptor in the human colon carcinoma cell subclone HT29-18-C1. AB - A lactoferrin receptor has been found on the brush-border membrane of intestinal epithelial cells of several species, including humans. A role for this receptor in intestinal iron absorption, which is well regulated in response to body iron stores, has been proposed. We have investigated the effect of intracellular iron depletion by picolinic acid, an iron chelator, on the cell surface binding of human lactoferrin to human enterocytes and its intracellular uptake, using HT29 18-C1 cells, an enterocyte-like differentiable cell line. The confluent cells exhibited 5.8 x 10(6) specific binding sites per cell for diferric human 125I labelled lactoferrin with relatively low affinity (Kd 8.4 x 10(-7) M). The addition of picolinic acid to the culture medium resulted in a concentration- and time-dependent increase in lactoferrin binding that was correlated with a decrease in intracellular iron content. The maximum effect of picolinic acid on lactoferrin binding (approx. 2-fold increase), which appeared between 12 and 18 h after its addition, was obtained at a picolinic acid concentration of 2 mM. Scatchard analysis showed that the enhanced lactoferrin binding resulted from an increase in the number of lactoferrin receptors rather than an alteration in the binding affinity for lactoferrin. The time-dependent effect of picolinic acid was completely abolished in the presence of 1 microM anisomycin, a protein synthesis inhibitor, indicating that ongoing protein synthesis is involved in this effect. The enhanced lactoferrin binding induced by picolinic acid produced an increase of approx. 30% in the uptake of lactoferrin-bound 59Fe, indicating the existence of functional receptors. These results suggest that biosynthesis of lactoferrin receptors in intestinal epithelial cells can be regulated in response to the levels of intracellular chelatable iron, consistent with intestinal iron absorption dependent on body iron stores. PMID- 7772017 TI - Characterization of the ATPase activity of P-glycoprotein from multidrug resistant Chinese hamster ovary cells. AB - P-Glycoprotein (Pgp) was isolated from CHRC5 membranes by selective detergent extraction and further purified by lentil lectin affinity chromatography. The purified product displayed a very high basal ATPase activity (1.65 mumol/min per mg protein in the absence of added drugs or lipids) with an apparent Km for ATP of 0.4 mM. There was no evidence of cooperativity, suggesting that the two ATP sites operate independently of each other. Pgp ATPase activity was stimulated by verapamil, trifluoperazine and colchicine, and inhibited by daunomycin and vinblastine. All drugs and chemosensitizers acted as mixed activators or inhibitors, producing changes in both the Vmax of the ATPase and the Km for ATP. ADP competitively inhibited Pgp ATPase, with a Ki of 0.2 mM. The macrolide antibiotics bafilomycin A1, concanamycin A and concanamycin B, inhibited Pgp ATPase at concentrations of 0.1-10 microM, and at an inhibitor:protein stoichiometry of 0.65-1.0 mumol/mg protein, which is at the low end of the range characteristic of P-type ATPases. Pgp ATPase was relatively selective for adenine nucleotides. Several phospholipids stimulated Pgp ATPase activity in a dose dependent manner, whereas others produced inhibition. Metabolic labelling showed that the endogenous phospholipids associated with purified Pgp consisted largely of phosphatidylethanolamine and phosphatidylserine, with only a small amount of phosphatidylcholine. 32P-Labelling studies indicated that purified Pgp was partially phosphorylated. It can be concluded that Pgp is a constitutively active, adenine nucleotide-specific ATPase whose catalytic activity can be modulated by both drugs and phospholipids. PMID- 7772015 TI - Parasite-regulated membrane transport processes and metabolic control in malaria infected erythrocytes. PMID- 7772019 TI - Characterization of ATP receptor responsible for the activation of phospholipase A2 and stimulation of prostaglandin E2 production in thymic epithelial cells. AB - In TEA3A1 rat thymic epithelial cells, ATP stimulates prostaglandin E2 (PGE2) production through activation of phospholipase A2 (PLA2) enzymic activity. The stimulation of PGE2 production tested with other nucleotides indicated the agonist potency of adenosine 5'-[gamma-thio]triphosphate (ATP[S]) > or = UTP > ATP, with ED50 of about 10 microM for ATP[S]. In TEA3A1 cells, cross-linking studies with ATP[35S] revealed the presence of four cell-surface cross-linked bands of 42 kDa, 53 kDa, 83 kDa and 100 kDa in Triton X-100 extracts of TEA3A1 cells by fluorography. Guanosine 5'-[gamma-thio]triphosphate specifically blocked the cross-linking of ATP[35S] to the 53 kDa, 83 kDa and 100 kDa ATP-binding proteins, and inhibited the ATP[S]-mediated stimulation of PGE2 production with an ED50 of about 25 microM. On the other hand, 2-methylthioadenosine triphosphate (2MeSATP) blocked ATP[35S] cross-linking to the 42 kDa protein, but had no effect on ATP[S]-mediated stimulation of PGE2 production. In a variant cell line, TEAvarl, derived from TEA3A1 cells that lost their response to ATP in the activation of PLA2, the presence of 83 kDa ATP-binding protein was not detected. Results from our study suggest that ATP activates PLA2 enzymic activity in TEA3A1 cells by binding to an atypical ATP receptor that has not been described previously. PMID- 7772020 TI - Cloning and expression of the carboxypeptidase gene from Aspergillus saitoi and determination of the catalytic residues by site-directed mutagenesis. AB - Carboxypeptidase from Aspergillus saitoi removes acidic, neutral and basic amino acids as well as proline from the C-terminal position at pH 2-5. cpdS, a cDNA encoding A. saitoi carboxypeptidase, was cloned and expressed. Analysis of the 1816-nucleotide sequence revealed a single open reading frame coding for 523 amino acids. When A. saitoi carboxypeptidase cDNA was expressed in yeast cells, carboxypeptidase activity was detected in the cell extract and was immunostained with a 72 kDa protein with polyclonal anti-(A. saitoi carboxypeptidase) serum. The recombinant enzyme treated with glycopeptidase F migrated with an apparent molecular mass of 60 kDa on SDS/PAGE, which was the same as that of the de-N glycosylated carboxypeptidase from A. saitoi. Site-directed mutagenesis of the cpdS indicated that Ser-153, Asp-357 and His-436 residues were essential for the enzymic catalysis. It can be concluded that A. saitoi carboxypeptidase has a catalytic triad comprising Asp-His-Ser and is a member of serine carboxypeptidase family (EC 3.4.16.1). PMID- 7772021 TI - Metabolic response of sheep skin to a chronic infusion of a variant of insulin like growth factor I. AB - The effects of a chronic (21-day) skin infusion of a variant of insulin-like growth factor I (IGF-I) (long-Arg3-IGF-I; LR3IGF-I) on short-term (48 h) responses of skin metabolism and 21-day plasma hormone concentration, wool follicle characteristics and wool production were investigated in well-fed castrated Romney sheep. A bilateral arteriovenous preparation was used to infuse LR3IGF-I continuously into the skin on one abdominal flank and saline into the other abdominal flank of six sheep; a further six sheep had one flank infused with saline (controls). LR3IGF-I caused an initial (4-24 h) reduction in the plasma concentrations of amino acids, especially tyrosine, valine and lysine, and, after 24 h, significant (P < 0.05) reductions in blood oxygen and plasma glucose concentrations. After 4 h of LR3IGF-I infusion, there was a significant increase in blood flow (P < 0.05) and oxygen uptake (P < 0.05), and net uptake of amino acids [which was significant (P < 0.05) for valine and phenylalanine] by the LR3IGF-I-infused skin was increased. Total uptake of phenylalanine for skin protein synthesis, measured using [3H]phenylalanine uptake, was also significantly increased after 4 and 24 h of infusion. After 48 h of infusion all LR3IGF-I-dependent measurements of metabolic parameters had fallen to preinfusion values. By day 7 of the 21-day infusion there was a significant (P < 0.05) decrease in circulating endogenous IGF-I in plasma of treated sheep compared with that of control sheep, followed by a significant (P < 0.05) increase between day 7 and 21. Plasma insulin levels followed a similar pattern. There was no change at any stage of infusion in IGF-binding proteins in the plasma of the two LR3IGF I-infused sheep tested, and it is concluded that LR3IGF-I caused a down regulation of the type-I IGF-I receptors followed by a rise in endogenous IGF-I concentration consequent on lack of feedback regulation. After 21 days of infusion there was no effect of LR3IGF-I on wool-follicle-bulb-cell mitotic rate, bulb diameter or wool production.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772022 TI - Amino acids important in enzyme activity and dimer stability for Drosophila alcohol dehydrogenase. AB - We have determined the nucleotide sequences of eight ethyl methanesulphonate induced mutants in Drosophila alcohol dehydrogenase (ADH), of which six were previously characterized by Hollocher and Place [(1988) Genetics 116, 253-263 and 265-274]. Four of these ADH mutants contain a single amino acid change: glycine 17 to arginine, glycine-93 to glutamic acid, alanine-159 to threonine, and glycine-184 to aspartic acid. Although these mutants are inactive, three mutants (Gly17Arg, Gly93Glu and Gly184Asp) form stable homodimers, as well as heterodimers with wild-type ADH, in which the wild-type ADH subunit retains full enzyme activity [Hollocher and Place (1988) Genetics 116, 265-274]. Interestingly, the Ala159Thr mutant does not form either stable homodimers or heterodimers with wild-type ADH, suggesting that alanine-159 is important in stabilizing ADH dimers. The mutations were analysed in terms of a three dimensional model of ADH using bacterial 20 beta-hydroxysteroid dehydrogenase and rat dihydropteridine reductase as templates. The model indicates that mutations in glycine-17 and glycine-93 affect the binding of NAD+. It also shows that alanine-159 is part of a hydrophobic anchor on the dimer interface of ADH. Replacement of alanine-159 with threonine, which has a larger side chain and can hydrogen bond with water, is likely to reduce the strength of the hydrophobic interaction. The three-dimensional model shows that glycine-184 is close to the substrate binding site. Replacement of glycine-184 with aspartic acid is likely to alter the position of threonine-186, which we propose hydrogen bonds to the carboxamide moiety of NAD+. Also, the negative charge on the aspartic acid side chain may interact with the substrate and/or residues in the substrate binding site. These mutations provide information about ADH catalysis and the stability of dimers, which may also be useful in understanding homologous dehydrogenases, which include the human 17 beta-hydroxysteroid, 11 beta-hydroxysteroid and 15 hydroxyprostaglandin dehydrogenases. PMID- 7772023 TI - Murine protein tyrosine phosphatase-PEST, a stable cytosolic protein tyrosine phosphatase. AB - We have isolated the murine cDNA homologue of the human protein tyrosine phosphatase PTP-PEST (MPTP-PEST) from an 18.5-day mouse embryonic kidney library. The cDNA isolated has a single open reading frame predicting a protein of 775 amino acids. When expressed in vitro as a glutathione S-transferase fusion protein, the catalytic domain (residues 1-453) shows intrinsic phosphatase activity. Reverse transcriptase PCR and Northern-blot analysis show that MPTP PEST mRNA is expressed throughout murine development. Indirect immunofluorescence in COS-1 cells against a heterologous epitope tag attached to the N-terminus of MPTP-PEST, together with cellular fractionation and Western-blot experiments from different murine cell lines, indicate that MPTP-PEST is a free cytosolic protein of 112 kDa. Finally, sequence analysis indicates that the C-terminal portion of the protein contains four regions rich in proline, glutamate, serine and threonine, otherwise known as PEST sequences. These are characteristic of proteins that display very short intracellular half-lives. Despite the presence of these motifs, pulse-chase labelling experiments demonstrate that MPTP-PEST has a half-life of more than 4 h. PMID- 7772024 TI - Mouse aggrecan, a large cartilage proteoglycan: protein sequence, gene structure and promoter sequence. AB - Seven genomic clones for mouse aggrecan core protein have been isolated including 3 kb of 5'- and 7 kb of 3'-flanking sequences. All exon sequences and their intron boundary sequences in these clones were identified and mapped by DNA sequencing. The gene spans at least 61 kb and contains 18 exons. Exon 1 encodes 5'-untranslated sequence and exon 2 contains a translation start codon, methionine. The coding sequence is 6545 bp for a 2132-amino-acid protein with calculated M(r) = 259,131 including an 18-amino-acid signal peptide. There is a strong correlation between structural domains and exons. Notably, the chondroitin sulphate domain consisting of 1161 amino acids is encoded by a single exon of 3.6 kb. Although link protein has similar structural domains and subdomains, the sequence identity and the organization of exons encoding the subdomains B and B' of G1 and G2 domains revealed a strong similarity of mouse aggrecan to both human versican and rat neurocan. Primer extension analysis identified four transcription start sites which are close together. The promoter sequence showed high G/C content (65%) and contained several consensus binding motifs for transcription factors including Sp-1 and the glucocorticoid receptor. There are stretches of sequences similar to the promoter region of both the type-II collagen and link protein genes. These sequences may be important for cartilage gene expression. PMID- 7772025 TI - Characterization of the manganese superoxide dismutase cDNA and gene from the human parasite Onchocerca volvulus. AB - The manganese-containing superoxide dismutase (MnSOD) is a major component of the cellular defence mechanisms against the toxic effects of the superoxide radical. Within the framework of studies on anti-oxidant enzymes and their protective role in the human parasitic nematode Onchocerca volvulus, sequences encoding the MnSOD were isolated and examined in this study. Degenerate primers were designed based upon conserved regions of MnSOD sequences from other organisms, and were used in PCR on reverse-transcribed O. volvulus total RNA and genomic DNA to identify partial cDNA and genomic DNA fragments encoding the O. volvulus MnSOD (OvMnSOD). The genomic DNA PCR product was used to screen an O. volvulus adult worm lambda unizap II cDNA library and the nucleotide sequence of the longest clone determined. The complete 5'-end of the OvMnSOD cDNA was obtained using the rapid amplification of cDNA ends (RACE) procedure with O. volvulus total RNA and was found to possess a spliced leader sequence at the 5'-terminus. The deduced primary sequence encodes a 25 kDa protein, which has the conserved residues required for enzyme activity and metal binding. The 24 N-terminal amino acids encoded by the OvMnSOD cDNA comprise a putative mitochondrial transit peptide. The OvMnSOD gene was also isolated from an O. volvulus adult worm lambda fix II genomic library, a restriction map was constructed and the nucleotide sequence determined. The OvMnSOD gene was found to possess five exons and four introns with consensus splice-site junctions. Potential regulatory elements were identified in the 5' genomic flanking sequence. Southern-blot analysis with total worm genomic DNA indicates a single-copy gene, with a restriction pattern consistent with that of the isolated gene. PMID- 7772026 TI - Probing the details of the HIV-1 Rev-Rev-responsive element interaction: effects of modified nucleotides on protein affinity and conformational changes during complex formation. AB - The solution structure of the human immunodeficiency virus type 1 (HIV-1) Rev responsive element (RRE) has been investigated by enzymic and chemical structural probing of a 71 nt RRE transcript. The minimum sequence information required to maintain recognition by the Rev protein has previously been mapped to a 29 nt stem-loop structure, known as minSLIIB. The key recognition target is a single stranded RNA bubble at the base of the RNA stem. The fine details of RNA recognition have been probed using chemically synthesized minSLIIBs containing variant base or sugar residues at sites within the bubble. These have been analysed by gel retardation assays and their relative affinities for Rev protein determined. Complex formation between the wild-type minSLIIB RRE and Rev protein was also monitored using CD spectroscopy, which suggests a change in RNA conformation upon Rev binding. The spectral change is consistent with localized melting of RNA, leading to a decrease in the level of base stacking and/or a change in base tilting, during formation of the complex. Deoxynucleotide substitutions on just one side, the 5' side, of the bubble inhibit the conformational change detected by CD. The data are consistent with a dynamic interaction between Rev and its target site. The contact points between Rev and the RRE were probed directly using photo-cross-linking with either ribo-5 bromouridine- or ribo-4-thiouridine-substituted minSLIIBs. The data are consistent with protein-RNA contacts at the bottom of the bubble. PMID- 7772028 TI - The temporal and cellular expression of c-fos and c-jun in mechanically stimulated rabbit latissimus dorsi muscle. AB - The levels of c-fos and c-jun mRNA were measured by reverse transcription PCR in the rabbit latissimus dorsi muscle following three separate training regimes, i.e. passive stretch, 10 Hz electrical stimulation or a combination of the two. Both c-fos and c-jun mRNA expression peaked at around 1 h after imposing stretch and at around 4.5-6 h after the initiation of electrical stimulation. The combined stretch/electrical stimulation regime induced biphasic expression of both c-fos and c-jun mRNA, with peaks coinciding temporally with those for the individual regimes. Immunostaining with anti-Fos and anti-Jun antibodies revealed the accumulation of these proteins in both myofibre and interstitial cell nuclei following passive stretch. In contrast, following electrical stimulation the localization of immunoreactive c-Fos and c-Jun proteins was predominantly in interstitial cell nuclei. c-Fos and c-Jun immunoreactivity was also clearly colocalized in a proportion of myonuclei from stretched muscle. These findings suggest that the rapid induction of c-fos and c-jun is an early event in response to mechanical stretch and might trigger [via activator protein-1 (AP-1) transcriptional factors] events leading to muscle fibre hypertrophy. However, the involvement of AP-1 in inducing the phenotypic changes in muscle fibres as a result of electrical stimulation appears less clear. PMID- 7772027 TI - Induction by prostaglandin A1 of haem oxygenase in myoblastic cells: an effect independent of expression of the 70 kDa heat shock protein. AB - Prostaglandins of the A type (PGA) induce the synthesis of 70 kDa heat shock proteins (hsp70) in a large variety of mammalian cells. Induction of hsp70 has been associated with a cytoprotective effect of PGA1 after virus infection or thermal injury. In the present report we provide evidence that, in murine myoblasts, PGA1 is not able to induce hsp70 expression, whereas it increases the synthesis of the constitutive protein, hsc70, and dramatically induces the synthesis of a 32 kDa protein (p32). The p32 protein has been identified as haem oxygenase. PGA1 acts at the transcriptional level by inducing haem oxygenase mRNA synthesis, and the signal for induction appears to be associated with decreased intracellular GSH levels. Haem oxygenase, a low-molecular-mass stress protein induced in mammalian cells by oxidant stress, is known to be part of a general inducible antioxidant defence pathway. The fact that prostaglandin synthesis is stimulated in muscle during contraction and in the heart in response to ischaemia raises the possibility that induction of haem oxygenase by PGA in myoblasts could be part of a protective mechanisms in operation during stress and hypoxia. PMID- 7772029 TI - Accumulation of phosphatidylalcohol in cultured cells: use of subcellular fractionation to investigate phospholipase D activity during signal transduction. AB - Phosphatidylalcohol accumulates as a product of a phospholipase D (PLD)-catalysed transphosphatidylation reaction in cells incubated in the presence of a primary alcohol. In the presence of ethanol the phorbol ester, phorbol 12-myristate 13 acetate (PMA), stimulated the accumulation of [3H]phosphatidylethanol (PEth) in HeLa cells prelabelled with [3H]palmitic acid. Radioactivity associated with PEth increased linearly during a 30 min incubation, indicating that a sustained activation of PLD is caused by PMA in these cells. This was accompanied by the membrane association of protein kinase C-alpha (PKC-alpha), the PKC isoform that recent studies indicate is involved in the activation of PLD. In similar experiments, the neuropeptide bradykinin stimulated an accumulation of PEth in 3T3 Li cells. The radioactivity associated with PEth increased to a maximal level at 30 s and plateaued after this time, suggesting that bradykinin induces only a transient activation of PLD in these cells. This is consistent with the effects of bradykinin on PKC-alpha, which underwent a rapid and transient association with cell membranes. The subcellular localization of PEth was examined using the technique of subcellular fractionation on Percoll density gradients to isolate organelle-enriched fractions from HeLa and 3T3 Li cells. An accumulation of [3H]PEth was measured in the plasma-membrane (PM)-enriched fractions of both HeLa and 3T3 Li cells after incubation with PMA and bradykinin respectively. This was accompanied by a time-dependent accumulation of [3H]PEth in the combined mitochondrial and endoplasmic reticulum (MER)-enriched fractions of both cell lines. PMA was also found to cause translocation of PKC-alpha to both the PM- and MER-enriched fractions in HeLa cells. However, bradykinin stimulated the translocation of PKC-alpha to the PM-enriched fractions only of 3T3 Li cells. The results show that PLD activation leads to the accumulation of PEth in both the PM and MER fractions. We therefore propose that either bradykinin activates a PM associated PLD and the PLD reaction product is rapidly translocated to other membrane systems or it activates an MER-associated PLD by a mechanism that does not involve PKC-alpha. PMID- 7772030 TI - Evidence for a protein S receptor(s) on human vascular smooth muscle cells. Analysis of the binding characteristics and mitogenic properties of protein S on human vascular smooth muscle cells. AB - The presence of specific binding sites for the coagulation factor protein S (PS) on the surface of human vascular smooth muscle cells (HVSMC) is described. The binding characteristics of 125I-PS to HVSMC were studied and found to be saturable, reversible and, as described by the Hill equation, co-operative (h 1.74; Kd 0.33 nM). Autoradiographic analysis of detergent extracts of HVSMC chemically cross-linked with 125I-PS and separated by SDS/PAGE revealed radioactivity associated with two proteins with apparent molecular masses of 220 and 230 kDa respectively. The mitogenic activity of PS on HVSMC was also investigated. Protein S was shown to stimulate DNA synthesis of growth-arrested HVSMC and to support their proliferation under low-serum conditions in a sustained and dose-dependent manner. PMID- 7772031 TI - Mechanism of reaction of allylamine with the quinoprotein methylamine dehydrogenase. AB - Allylamine did not serve as an efficient substrate for methylamine dehydrogenase (EC 1.4.99.3) in a steady-state assay of activity and appeared to act as a competitive inhibitor of methylamine oxidation by methylamine dehydrogenase. Transient kinetic studies, however, revealed that allylamine rapidly reduced the tryptophan tryptophylquinone (TTQ) cofactor of methylamine dehydrogenase. The rate of TTQ reduction by allylamine was 322 s-1, slightly faster than the rate of reduction by methylamine. These data were explained by a kinetic mechanism in which allylamine and methylamine are alternative substrates for methylamine dehydrogenase. The apparent competitive inhibition by allylamine is due to a very slow rate of release of the aldehyde product, 0.28 s-1, relative to a rate of 18.6 s-1 for the release of the aldehyde product of methylamine oxidation. A reaction mechanism is proposed for the oxidative deamination of allylamine by methylamine dehydrogenase. This mechanism is discussed in relation to the reaction mechanisms of topa-bearing quinoprotein amine oxidases, the flavoprotein monoamine oxidase and the mammalian semicarbazide-sensitive amine oxidase. PMID- 7772032 TI - Effects of polycations on Ca2+ binding to the Ca(2+)-ATPase. AB - Spermine and polyarginine have been shown to increase the rate of dissociation of Ca2+ from the Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum. They also decrease the affinity of the ATPase for Mg2+ as detected by changes in the fluorescence intensity of the ATPase labelled with 4-(bromomethyl)-6,7 dimethoxycoumarin (DMC). Polyarginine itself also decreases the fluorescence intensity of DMC-labelled ATPase. These results are consistent with binding of spermine and polyarginine to a gating site controlling the rate of access of Ca2+ to its binding sites on the ATPase. A basic peptide PLN-(1-25) corresponding to residues 1-25 of phospholamban had no effect on the rate of dissociation of Ca2+ or on the fluorescence of DMC-labelled ATPase. Spermine, polyarginine and PLN-(1 25) all increased the equilibrium constant E1/E2, and spermine and polyarginine increased the rate of Ca2+ binding to the ATPase, consistent with an increase in the rate of the E2-->E1 transition. Spermine displaced Tb3+ and Ruthenium Red from the ATPase, consistent with binding in the stalk region of the ATPase. Polyarginine and PLN-(1-25), however, had no effect on Tb3+ or Ruthenium Red binding, suggesting a greater specificity in binding basic peptides to the ATPase than spermine. PMID- 7772033 TI - N-acetyl-D-neuraminic acid synthesis in Escherichia coli K1 occurs through condensation of N-acetyl-D-mannosamine and pyruvate. AB - Two enzymes have been found to be involved in bacterial N-acetyl-D-neuraminic acid (NeuAc) synthesis: NeuAc synthase, which condenses N-acetyl-L,D-mannosamine and phosphoenolpyruvate, and NeuAc lyase or NeuAc aldolase, which condenses N acetyl-D-mannosamine and pyruvate. When we used Escherichia coli K1 crude extracts, we observed the generation of NeuAc in the presence of N acetylmannosamine and both phosphoenolpyruvate (NeuAc synthase activity) or pyruvate (NeuAc lyase activity). However, when crude extracts were fractionated by Sephacryl S-200 chromatography, NeuAc synthase activity disappeared. A chromatographic peak of NeuAc synthase activity was detected when column fractions were re-tested in the presence of the active NeuAc lyase peak. Furthermore, crude extracts converted phosphoenolpyruvate into pyruvate. Pyruvate depletion, due to the addition of pyruvate decarboxylase to the NeuAc synthase reaction mixture, blocked NeuAc formation. Moreover, after NeuAc lyase immunoprecipitation no NeuAc synthase was detected. These findings suggest that NeuAc synthase is not present in E. coli K1 and therefore that NeuAc lyase is the only enzyme responsible for NeuAc synthesis in this bacterium. PMID- 7772035 TI - Differential effects of distamycin analogues on amplification of human gene sequences by polymerase-chain reaction. AB - In this report we analyse the effects of distamycin and five distamycin analogues on amplification by polymerase-chain reaction (PCR) of two gene sequences displaying a different A+T/G+C content. The first was a 5' region of the human oestrogen receptor (ER) gene, containing a (TA)26 stretch; the second was a CG rich sequence of the human Ha-ras oncogene. The results obtained unequivocally demonstrate that the addition of one pyrrole ring significantly improves the ability of distamycin derivatives to interfere with PCR-mediated amplification of the human ER genomic region carrying a (TA)26 stretch. The distamycin analogues analysed differ in the number of pyrrole rings and in the presence of an N formyl, an N-formimidoyl or a retroamide group at position X1. Among compounds carrying the same number of pyrrole rings, those carrying an N-formyl or an N formimidoyl group retain a similar inhibitory activity. The retroamide analogues, on the contrary, are much less efficient in inhibiting PCR-mediated amplification of the 5'ER region. With respect to sequence selectivity both distamycin and distamycin analogues exhibit a sequence preference, since they do not inhibit PCR amplification of Ha-ras CG-rich gene regions, with the exception of a distamycin analogue carrying four pyrrole rings. PMID- 7772034 TI - Enhanced hydrolysis of phosphatidylcholine by human group II non-pancreatic secreted phospholipase A2 as a result of interfacial activation by specific anions. Potential role of cholesterol sulphate. AB - The extracellular concentration of the Group II human non-pancreatic secreted phospholipase A2 (hnpsPLA2) is elevated in a variety of inflammatory disorders. This enzyme is remarkable because it demonstrates almost zero activity with egg phosphatidylcholine (PC) or synthetic dioleoyl-phosphatidylcholine (DOPC) as substrate, but expresses high activity with the anionic phospholipid dioleoyl phosphatidylglycerol (DOPG), a feature shared with the Group II enzyme from rat liver. The presence of certain membrane-bound anions can enhance hydrolysis of PC by the mammalian secreted PLA2S. In this study the ability of various non-polar anions to stimulate DOPC hydrolysis by secreted PLA2S has been investigated. The naturally occurring membrane anion, cholesterol sulphate, was particularly effective in stimulating the hydrolysis of both DOPC and also 1-stearoyl-2 arachidonyl phosphatidylcholine by hnpsPLA2. Activation of DOPC hydrolysis was also achieved with dioleoyl-phosphatidylserine (DOPS); however, DOPS was less effective than cholesterol sulphate. In contrast, the dianion dioleoyl phosphatidic acid, a known activator of pig pancreatic PLA2, failed to activate the human enzyme. It remains to be established whether cell plasma-membrane hydrolysis by extracellular hnpsPLA2 can be activated in vivo by the presence of suitable membrane anions such as cholesterol sulphate and thus promote an inflammatory response within the cell. PMID- 7772036 TI - DNase I hypersensitivity sites and nuclear protein binding on the fatty acid synthase gene: identification of an element with properties similar to known glucose-responsive elements. AB - We have shown previously that fatty acid synthase (FAS) gene expression is positively regulated by glucose in rat adipose tissue and liver. In the present study, we have identified in the first intron of the gene a sequence closely related to known glucose-responsive elements such as in the L-pyruvate kinase and S14 genes, including a putative upstream stimulatory factor/major late transcription factor (USF/MLTF) binding site (E-box) (+ 292 nt to + 297 nt). Location of this sequence corresponds to a site of hypersensitivity to DNase I which is present in the liver but not in the spleen. Moreover, using this information from a preliminary report of the present work, others have shown that a + 283 nt to + 303 nt sequence of the FAS gene can confer glucose responsiveness to a heterologous promoter. The protein binding to this region has been investigated in vitro by a combination of DNase I footprinting and gel retardation experiments with synthetic oligonucleotides and known nuclear proteins. DNase I footprinting experiments using a + 161 nt to + 405 nt fragment of the FAS gene demonstrate that a region from + 290 nt to + 316 nt is protected by nuclear extracts from liver and spleen. This region binds two ubiquitous nuclear factors, USF/MLTF and the CAAT-binding transcription factor/nuclear factor 1 (CTF/NF1). Binding of these factors is similar in nuclear extracts from liver which does or does not express the FAS gene as observed for glucose responsive elements in the L-pyruvate kinase and S14 genes. This suggests a posttranslational modification of a factor of the complex after glucose stimulation. PMID- 7772037 TI - Inhibition of proteolysis by cell swelling in the liver requires intact microtubular structures. AB - In the perfused rat liver, proteolysis is inhibited by cell swelling in response to hypo-osmotic media, glutamine and insulin. Colchicine, an inhibitor of microtubules, did not affect cell swelling in response to these agonists. However, the antiproteolytic action of these effectors was largely blunted in the presence of colchicine or the microtubule inhibitors colcemid and taxol. On the other hand, inhibition of proteolysis by phenylalanine, asparagine or NH4Cl, i.e. compounds which exert their antiproteolytic effects by mechanisms distinct from cell swelling, was not sensitive to colchicine. Swelling-induced inhibition of proteolysis was not affected by cytochalasin B. The anti-proteolytic effect of hypo-osmotic cell swelling and insulin was largely abolished in freshly isolated rat hepatocytes; however, it reappeared upon cultivation of the hepatocytes for 6 10 h. The restoration of the sensitivity of proteolysis to cell volume changes was accompanied by a progressive reorganization of microtubule structures, as shown by immunohistochemical staining for tubulin. It is concluded that intact microtubules are required for the control of proteolysis by cell volume, but not for the control of proteolysis by phenylalanine, asparagine or NH4Cl. These findings may explain why others [Meijer, Gustafson, Luiken, Blommaart, Caro, Van Woerkom, Spronk and Boon (1993) Eur. J. Biochem. 215, 449-454] failed to detect an antiproteolytic effect of hypo-osmotic exposure of freshly isolated hepatocytes. This effect, however, which is consistently found in the intact perfused rat liver, also reappeared in isolated hepatocytes when they were allowed to reorganize their microtubular structures in culture. PMID- 7772038 TI - Quantification in vivo of the effects of different types of dietary fat on the loci of control involved in hepatic triacylglycerol secretion. AB - Polyunsaturated fatty acids (PUFA) have been suggested to exert their hypotriglyceridaemic effect through several possible mechanisms that would be expected to decrease the rate of hepatic very-low-density-lipoprotein triacylglycerol secretion. We have quantified the role played in vivo by changes in the pattern of partitioning of (i) acyl-CoA between oxidation and esterification, (ii) diacylglycerol between synthesis of triacylglycerol and of the major phospholipids, and (iii) triacylglycerol between secretion and storage within the liver, in response to two dietary levels of n-6 and n-3 PUFA. In order to achieve this we used the technique of selective labelling of hepatic fatty acids in vivo. Compared with a predominantly saturated fatty acid diet, both n-6 and n-3 PUFA intake resulted in a decrease in the proportion of acyl moieties that were secreted by the liver, through an increased diversion of acyl-CoA towards oxidation and a lower fractional rate of secretion of newly synthesized triacylglycerol. In addition, a diet rich in n-3 fatty acids resulted not only in a greater magnitude of these effects but also in a doubling of the partitioning of diacylglycerol towards phospholipid labelling. It is shown that the overall 50% reduction achieved by fish oil feeding in the proportion of acyl groups that were secreted by the liver was distributed over all three branch points. The contribution of each of these adaptations was quantified. The application of such an approach, i.e. the localization and in vivo quantification of the importance of loci of control, in studies on dietary and pharmacological agents that affect lipaemia, is discussed. PMID- 7772039 TI - Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression. AB - The action of endotoxin lipopolysaccharide (LPS) on hepatic Zn uptake was examined in mice lacking expression of metallothionein (MT)-1 and MT-II genes. Hepatic Zn concentrations, which in normal control mice increased by a mean 29% (MT elevated 20-fold) 16 h post-LPS exposure, did not increase in MT-null mice. Plasma Zn fell by 68% in controls and 32% in MT-null mice. The time course of LPS action in normal mice was characterized by a rapid reduction (-74% at 4 h, -81% at 8 h) and partial recovery (-39% at 24 h) in plasma Zn, with a progressive increase over 24 h in hepatic concentrations of MT (by 36-fold) and Zn (by 40%). In contrast, the MT-null mice had a linear decrease in plasma Zn (-15% at 8 h, 41% at 24 h) and early loss of Zn from the liver. The Zn changes seen in MT-null mice were largely attributable to LPS-associated anorexia. Food deprivation (20 h) alone caused respective 14% and 30% decreases in hepatic and plasma Zn concentrations and a 27% reduction in total liver Zn reserves, whereas fasted normal mice conserved Zn with a 4-fold increase in hepatic MT. This study confirms that MT synthesis is essential for endotoxin-induced liver Zn accumulation. PMID- 7772040 TI - Catalytic activity of bovine seminal ribonuclease is essential for its immunosuppressive and other biological activities. AB - Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with special biological properties, including potent immunosuppressive activity. A mutant BS RNase was created in which His-119, the active-site residue that acts as a general acid during catalysis, was changed to an aspartic acid. H119D BS-RNase formed a dimer with quaternary structure similar to that of the wild-type enzyme but with values of kcat. and kcat./Km for the cleavage of UpA [uridylyl(3'- >5')adenosine] that were 4 x 10(3)-fold lower. The mutant protein also demonstrated dramatically decreased immunosuppressive, anti-tumour, aspermatogenic, and embryotoxic activities. The catalytic activity of BS-RNase is therefore necessary for its special biological properties. PMID- 7772042 TI - Inhibition of myeloperoxidase by benzoic acid hydrazides. AB - Myeloperoxidase is the most abundant protein in neutrophils and catalyses the conversion of H2O2 and chloride into HOCl. To help clarify the role of this enzyme in bacterial killing and inflammation, a specific and potent inhibitor needs to be identified. We have studied a series of benzoic acid hydrazides and found that in general they inhibit the peroxidation activity of myeloperoxidase with an IC50 value of less than 10 microM. The IC50 values of derivatives with substituents containing oxygen or nitrogen were related to their Hammett substituent constants. This indicates that myeloperoxidase oxidizes the hydrazide group of these compounds, and the degree to which they inhibit the enzyme is dependent on the ease of their oxidation. Unsubstituted benzoic acid hydrazide and its 4-chloro derivative were poor inhibitors of peroxidation. Thus it is likely that hydrogen-bonding of the enzyme to substituents containing oxygen or nitrogen increases the binding affinity of the hydrazides and enhances their oxidation by myeloperoxidase. 4-Aminobenzoic acid hydrazide (ABAH) was the most potent inhibitor of peroxidation. It irreversibly inhibited HOCl production by the purified enzyme, having an IC50 value of 0.3 microM. With neutrophils stimulated with opsonized zymosan or phorbol myristate acetate, ABAH inhibited HOCl production by up to 90% and the IC50 values were 16 microM and 2.2 microM respectively. In the presence of superoxide dismutase, these values decreased to 6.4 microM and 0.6 microM respectively. ABAH had no effect on superoxide radical (O2-.) production and degranulation by neutrophils, nor did it inhibit catalase or glutathione peroxidase. Thus ABAH is an effective and selective inhibitor that should be useful for determining the contribution of myeloperoxidase to oxidant mediated reactions of neutrophils. PMID- 7772041 TI - Purification and properties of lysophospholipase isoenzymes from pig gastric mucosa. AB - Two lysophospholipases, named gastric lysophospholipases I and II (enzymes I and II), were purified 3730- and 2680-fold from pig gastric mucosa. The preparations showed 22 and 23 kDa single protein bands on SDS/PAGE respectively. Both enzymes lacked transacylase activity and appeared to exist as monomers. Their activities were not affected by Ca2+, Mg2+ or EDTA. Enzyme I was most active at pH 8.5 and hydrolysed a variety of lysophospholipids including acidic lysophospholipids and the acyl analogue of platelet-activating factor, whereas enzyme II was most active at pH 8 and its activity was confined to lysophosphatidylcholine and lysophosphatidylethanolamine. When 1-palmitoylglycerophosphocholine was used as substrate, enzymes I and II showed half-maximal activities at 11 and 12 microM respectively. The enzymes exhibited no phospholipase B, lipase or general esterase activity. Enzyme II was significantly inhibited by lysophosphatidic acid whereas enzyme I was only moderately inhibited. Peptide mapping with V8 protease and papain revealed structural dissimilarity between the two enzymes. Antiserum raised against enzyme I did not recognize enzyme II, but did recognize the small sized lysophospholipase purified from rat liver. Anti-(enzyme II) consistently did not cross-react with enzyme I or the liver enzyme. These antisera specifically recognized neither the 60 kDa lysophospholipase transacylase purified from liver nor any peritoneal macrophage protein. Thus gastric mucosa contains two different small-sized lysophospholipases: one is closely related to the small-sized lysophospholipase of liver, but the other appears to be a novel isoform. PMID- 7772044 TI - Simultaneous purification of biotin-binding proteins-I and -II from chicken egg yolk and their characterization. AB - Chicken egg yolk biotin-binding protein-I (BBP-I) has been purified to homogeneity along with the tetrameric BBP-II by a common protocol. The purification includes delipidation of egg yolk by butanol extraction, DEAE Sephacel chromatography, treatment with guanidinium chloride and biotin aminohexyl-Sepharose affinity chromatography. The identity of purified BBP-I was ascertained by its physicochemical properties as well as by its immunological cross-reactivity and precursor-product relationship with BBP-II. PMID- 7772043 TI - Study of the rat liver S-adenosylmethionine synthetase active site with 8-azido ATP. AB - The active site of rat liver S-adenosylmethionine synthetase was studied using 8 azido ATP, a photolabile analogue of ATP. Both forms of the enzyme, tetramer and dimer, could be labelled by using concentrations of the analogue similar to the KmATP values for each form, 350 microM and 1 mM respectively. Labelling of both S adenosylmethionine synthetase forms with 8-azido [alpha-32P]ATP, followed by tryptic digestion and purification by HPLC, afforded one specifically labelled peptide in each case. Identification of the labelled peptide by amino acid analysis and peptide sequencing, and comparison with the enzyme sequence, indicated that the same peptide (267-286) was modified in both enzyme forms. The results are discussed on the basis of the high degree of similarity that this peptide shows in all the known S-adenosylmethionine synthetase sequences. PMID- 7772045 TI - The complete amino acid sequence confirms the presence of pseudoazurin in Thiosphaera pantotropha. AB - The complete amino acid sequence, obtained by direct protein sequencing, of the pseudoazurin from Thiosphaera pantotropha is reported. It shows sequence identities varying from 46 to 66% with previously sequenced pseudoazurins. Previously identified conserved residues with key functions in pseudoazurins are found in the protein from T. pantotropha with the exception of glycine-39, the carbonyl group of which has been considered as a ligand to the copper, which is replaced by a serine residue. Electrospray-ionization MS (ESI-MS) has shown that pseudoazurin from T. pantotropha often contains two polypeptide species differing in molecular mass by 16 Da, presumably owing to oxidation of a methionine residue to a sulphoxide derivative. These two species have different endoproteinase Arg-C digestion patterns. Conditions for ESI-MS were identified that permitted either the retention or the loss of the single copper ion associated with the pseudoazurin. The aberrant tendency of T. pantotropha pseudoazurin to form a disulphide-bridged dimer on SDS/PAGE under some conditions is described. PMID- 7772046 TI - Ca2+ concentration during binding determines the manner in which annexin V binds to membranes. AB - Annexins are a family of calcium-binding proteins that have been implicated in a wide range of intracellular processes. We have previously reported that stimulation of platelets with thrombin can induce the association of intracellular annexin V with membranes in two distinct ways. First, in such a way that it can be eluted from the membrane with EGTA and secondly in a manner such that it is tightly bound to the membrane and requires the non-ionic detergent Triton X-100 for its solubilization. We report that exposure of platelets to the calcium ionophore A23187 mimics the relocation induced by stimulation with thrombin. In separate experiments we demonstrate that a calcium ion concentration [Ca2+] of 0.8 microM is sufficient for maximum binding of the EGTA-resistant form to membranes. In contrast a higher [Ca2+] was required to induce maximal binding of the annexin V which could be extracted with EGTA. We demonstrate that following temperature-induced phase separation in Triton X-114, the membrane associated annexin V partitions predominantly into the aqueous phase. We also show that the isoelectric point of annexin V does not change following membrane association. These observations suggest that a covalent modification, of annexin V itself, is not responsible for its association with the membrane. Millimolar [Ca2+] is required for maximal binding of purified annexin V to phospholipid vesicles. We show that binding to phospholipids can be reversed entirely by subsequent treatment with EGTA. This suggests that the EGTA-resistant form of annexin V is binding to a membrane component other than phosphatidylserine. Annexin V has previously been shown to bind to protein kinase C. Relocation of annexin V to membranes paralleled that of protein kinase C in thrombin-stimulated cells but not in cells treated with A23187, suggesting that these proteins are not functionally linked in platelet activation. Using bifunctional cross-linking reagents we have identified an 85 kDa complex containing annexin V. This may represent an association between annexin V and an annexin V-binding protein with a molecular mass of approximately 50 kDa. PMID- 7772047 TI - Differential localization of the mRNA of the M and B isoforms of creatine kinase in myoblasts. AB - Creatine kinase (CK) plays an important role in buffering ATP and ADP levels in tissues which have intermittently high and fluctuating energy demands, such as skeletal muscle. This buffering function has a spatial, as well as a temporal aspect, which is dependent on the localization of different enzyme isoforms within the cell. We show here, by in situ hybridization, that the mRNAs for the cytoplasmic isoforms of CK are differentially localized in a mouse myoblast cell line (C2C12). The mRNA for the M form is localized at the cell periphery, while that for the B form is localized in the perinuclear region. Deletion of segments of the 3' untranslated regions of these mRNAs or swapping of these segments between the mRNAs for the two isoforms demonstrated that localization signals lie within these regions. Localization appears to be tissue-specific, since both the M and B mRNAs were distributed uniformly over the cytoplasm in a non-muscle cell line. These results, in conjunction with other studies which have shown that mRNA localization can lead to co-localization of the encoded protein, suggest that the localization of the mRNAs for the cytoplasmic isoforms of CK may be involved in the localization of the enzymes themselves. PMID- 7772048 TI - Localization of Ca(2+)-dependent conformational changes of calretinin by limited tryptic proteolysis. AB - Calretinin is an EF-hand Ca(2+)-binding protein expressed predominantly in some neurons. We have found that the tryptic digestion pattern of rat recombinant calretinin depends on Ca2+ concentration as determined by SDS/PAGE, amino-acid sequence analysis and electrospray-ionization MS. Ca(2+)-saturated calretinin was cleaved between amino acids 60 and 61 to yield two fragments, which accumulated during cleavage. Small amounts of the larger fragment (amino acid residues 61 271) were further cleaved from the C-terminal end. Ca(2+)-free calretinin was also cleaved between residues 60 and 61; however, under the latter conditions the fragment 61-271 was further cleaved from the N-terminal end. Native rat calretinin was cleaved by trypsin in a similar Ca(2+)-dependent fashion. All identified fragments of recombinant calretinin bound 45Ca2+ on nitrocellulose filters, although to a different extent. The 61-271 fragment was released by EGTA from an octyl-agarose column in a manner similar to intact calretinin, while fragment 61-233 was not eluted by EGTA. These observations show that there are trypsin cleavage sites in calretinin that are available regardless of Ca2+ binding, other sites that are completely protected against trypsin on Ca(2+) binding and sites which become partially available on Ca(2+)-binding. Together these data show that calretinin changes its conformation on Ca2+ binding and identify the regions which are exposed in apo and Ca(2+)-bound form. PMID- 7772049 TI - Expression of the human gene coding for the alpha-chain of C4b-binding protein, C4BPA, is controlled by an HNF1-dependent hepatic-specific promoter. AB - C4b-binding protein (C4BP) is an abundant oligomeric plasma glycoprotein which controls the activation of the complement cascade through the classical pathway. In humans, the majority form of C4BP is composed of seven alpha-chains and one beta-chain, covalently linked by their C-termini. C4BP is mainly expressed in the liver. We have previously cloned and characterized the structure of the genes encoding the alpha and beta chains, C4BPA and C4BPB, respectively. Here we addressed the characterization of the mechanisms controlling the hepatic restricted expression of the C4BPA gene. We found that the C4BPA promoter is contained within the first 369 bp upstream of the transcription start site. The activity of this promoter is restricted to hepatic cells in transfection experiments. The hepatic transcription factor HNF1 interacts with a region of this promoter at -38 bp. This region is absolutely required for the activity of this promoter, suggesting that HNF1 is essential for the hepatic activity of the C4BPA promoter. We speculate that this extreme requirement of HNF1 for the activity of the human C4BPA promoter is related to the fact that this promoter lacks a TATA box. PMID- 7772050 TI - Functional differences between dimeric and octameric mitochondrial creatine kinase. AB - Mitochondrial creatine kinase (Mi-CK) consists of octameric and dimeric molecules that are interconvertible. In the present study, the kinetic properties of purified chicken heart Mi-CK (Mib-CK) dimers and octamers were investigated separately under highly controlled conditions. Gel-permeation chromatography was performed before and after kinetic measurements in order to clearly define the proportions of octamers and dimers. 'Dimeric' Mi-CK solutions consisted of > or = 90% dimers throughout the experiment whereas 'octameric' Mi-CK solutions consisted in the beginning of 90% octamers, but upon measuring with the highest concentrations of creatine (Cr) and ATP approximately one-third of the octamers dissociated into dimers. These proper controls enabled us to pinpoint the observed kinetic differences between dimers and octamers solely to the oligomeric state of Mib-CK. Both dimeric and octameric Mi-CK displayed synergism in substrate binding (Kd values are higher than Km values), meaning that binding of the first substrate facilities subsequent binding of the second substrate. Most interestingly, Km(Cr) and Kd(Cr) values are both 2-3 times higher for octameric than for dimeric Mi-CK. Thus, at low Cr concentrations, the dimer is kinetically favoured for the forward direction of the reaction (phosphorylcreatine synthesis) compared with the octamer. The possible physiological significance of the lower Kd(Cr) value of dimeric versus octameric Mib-CK, as well as the apparent negative cooperativity of ATP binding at higher [Cr], are discussed within the context of a possible functional role for dimeric Mib-CK in vivo. PMID- 7772051 TI - Glutamine transport by vesicles isolated from tumour-cell mitochondrial inner membrane. AB - Mitochondrial-inner-membrane vesicles, isolated from Ehrlich ascites carcinoma cells by titration with detergents, accumulated L-glutamine by a very efficient transport system. The vesicles lack any phosphate-activated glutaminase activity, allowing measurement of transport rates without interference by L-glutamine metabolism. The time course of the transport was linear for the first 60 s, reaching a steady state after 120 min. L-Glutamine transport showed co operativity, with a Hill coefficient of 2.2; the kinetic parameters S0.5 and Vmax had values of 5 mM and 26 nmol/30 s per mg of protein respectively. The pH dependence curve showed a bell shape, with a pH optimum about 8.0. The uptake of L-glutamine was not affected by the presence of a 50-fold molar excess of D glutamine, L-cysteine, L-histidine, L-alanine, L-serine and L-leucine, whereas L glutamate behaved as a poor inhibitor. The structural analogue L-glutamate gamma hydroxamate (5mM) inhibited the net uptake by 68%; interestingly, other analogues (6-diazo-5-oxo-L-norleucine, acivicin and L-glutamate gamma-hydrazide) were ineffective. The impermeant thiol reagent p-chloromercuriphenylsulphonic acid (0.5mM) completely abolished the mitochondrial L-glutamine uptake; in contrast, other thiol reagents (mersalyl and N-ethylmaleimide) did not significantly affect the transport. These data confirm the existence of a specific transport system with high capacity for L-glutamine in the mitochondrial inner membrane, a step preceding the highly operative glutaminolysis in tumour cells. PMID- 7772052 TI - Molecular cloning and characterization of ornithine decarboxylase cDNA of the nematode Panagrellus redivivus. AB - In a PCR with degenerate primers encoding highly conserved amino acids within ornithine decarboxylases (ODCs) of several organisms, a fragment of the ODC gene of the free-living nematode Panagrellus redivivus was isolated. Northern blot analysis revealed a single 1.7 kb transcript in a mixed-stage population of animals. From this RNA source, a cDNA library was constructed and screened with the PCR fragment. Several cDNA clones were isolated, one of which encodes the complete 435-amino-acid ODC enzyme with a calculated molecular mass of 47.1 kDa. The P. redivivus ODC possesses 126 of the 136 highly conserved amino acids in the enzymes from fungi, invertebrates and vertebrates. Functional amino acids are conserved, suggesting that the two active sites of the P. redivivus ODC are formed at the interface of a homodimer, as described for mammalian ODCs. PMID- 7772054 TI - Steps involved in activation of the complex of pro-matrix metalloproteinase 2 (progelatinase A) and tissue inhibitor of metalloproteinases (TIMP)-2 by 4 aminophenylmercuric acetate. AB - Tissue inhibitor of metalloproteinases (TIMP)-2 forms a noncovalent complex with the precursor of matrix metalloproteinase 2 (proMMP-2, progelatinase A) through interaction of the C-terminal domain of each molecule. We have isolated the proMMP-2-TIMP-2 complex from the medium of human uterine cervical fibroblasts and investigated the processes involved in its activation by 4-aminophenylmercuric acetate (APMA). The treatment of the complex with APMA-activated proMMP-2 by disrupting the Cys73-Zn2+ interaction of the zymogen. This is triggered by perturbation of the proMMP-2 molecule, but not by the reaction of the SH group of Cys73 with APMA. The 'activated' proMMP-2 (proMMP-2*) formed a new complex with TIMP-2 by binding to the N-terminal inhibitory domain of the inhibitor without processing the propeptide. Thus the APMA-treated proMMP-2*-TIMP-2 complex exhibited no gelatinolytic activity. In the presence of a small amount of free MMP-2, however, proMMP-2* in the complex was converted into the 65 kDa MMP-2 by proteolytic attack of MMP-2, but the complex did not exhibit gelatinolytic activity. The gelatinolytic activity detected after APMA treatment was solely derived from the activation of free proMMP-2. The removal of the propeptide of the proMMP-2* bound to TIMP-2 was also observed by MMP-3 (stromelysin 1), but not by MMP-1 (interstitial collagenase). MMP-3 cleaved the Asn80-Tyr81 bond of proMMP 2*. On the other hand, when MMP-3 was incubated with the proMMP-2-TIMP-2 complex, it bound to TIMP-2 and rendered proMMP-2 readily activatable by APMA. These results indicate that the blockage of TIMP-2 of the complex with an active MMP is essential for the activation of proMMP-2 when it is complexed with TIMP-2. PMID- 7772055 TI - Effects of magnesium on cyclic GMP hydrolysis by the bovine retinal rod cyclic GMP phosphodiesterase. AB - Knowledge of the kinetics of the rod cyclic GMP phosphodiesterase is essential for understanding the kinetics and gain of the light response. Therefore, the interactions between Mg2+, cyclic GMP, and purified, trypsin-activated bovine rod cyclic GMP phosphodiesterase (EC 3.1.4.17) were examined. The effects of Mg2+ and of cyclic GMP on the rod phosphodiesterase activity were mutually concentration dependent. Formation of a free Mg-cyclic GMP complex is unlikely due to its high dissociation constant (Kd = 19 mM). Plots of 1/velocity versus 1/[cyclic GMP] as a function of [Mg2+] and 1/velocity versus 1/[Mg2+] as a function of [cyclic GMP] intersected to the left of the 1/velocity axis. This is consistent with the formation of a ternary complex between the phosphodiesterase, Mg2+, and cyclic GMP. A competitive inhibitor of the phosphodiesterase relative to cyclic GMP, 3 isobutyl-1-methylxanthine, non-competitively inhibited the enzyme relative to Mg2+, Pb2+, a competitive inhibitor of the phosphodiesterase relative to Mg2+ [D. Srivastava, R.L. Hurwitz and D. A. Fox (1995) Toxicol. Appl. Pharmacol, in the press] non-competitively inhibited the enzyme relative to cyclic GMP. Collectively these results are suggestive of a rapid equilibrium random binding order of Mg2+ and cyclic GMP to the rod phosphodiesterase. PMID- 7772053 TI - The haem b558 component of the cytochrome bd quinol oxidase complex from Escherichia coli has histidine-methionine axial ligation. AB - The cytochrome bd ubiquinol oxidase from Escherichia coli is induced when the bacteria are cultured under microaerophilic or low-aeration conditions. This membrane-bound respiratory oxidase catalyses the two-electron oxidation of ubiquinol and the four-electron reduction of dioxygen to water. The oxidase contains three haem prosthetic groups: haem b558, haem b595 and haem d. Haem d is the oxygen binding site, and it is likely that haem d and b595 form a bimetallic site in the enzyme. Haem b558 has been previously characterized spectroscopically as being low spin and has been shown to be located within subunit I (CydA) of this two-subunit enzyme. It is likely that haem b558 is associated with the quinol oxidation site, which has also been shown to be within subunit I. In a previous effort to locate the specific amino acids axially ligated to haem b558, all six histidines within subunit I were altered by site-directed mutagenesis. Only one, histidine-186, was identified as a likely ligand to haem b558. Hence it was suggested that haem b558 could not have bis(histidine) ligation. In the current work, a combination of low-temperature near-infrared magnetic circular dichroism (NIR-MCD) and EPR spectroscopies have been employed to identify the nature of the haem b558 axial ligands. The NIR-MCD spectrum at cryogenic temperatures is dominated by the low-spin haem b558 component of the complex, and the low-energy band near 1800 nm is strong evidence for histidine-methionine ligation. It is concluded that haem b558 is ligated to histidine-186 plus one of the methionines located within subunit I of the oxidase. PMID- 7772056 TI - Role of the promoter in the sensitivity of human thymidine kinase to lack of Zn2+. AB - Previous studies had indicated that lack of Zn2+ inhibits the expression of thymidine kinase activity and produces a corresponding reduction in the concentration of its mRNA. The present investigations have shown that with human thymidine kinase this is associated with increased binding of a specific protein to the gene's promoter in the region between -55 and -83 bp 5' to the transcription initiation site. A second binding site for the protein is present within the sixth exon of the human thymidine kinase gene. PMID- 7772057 TI - Chimeric constructs show that the unique N-terminal domain of the cyclic AMP phosphodiesterase RD1 (RNPDE4A1A; rPDE-IVA1) can confer membrane association upon the normally cytosolic protein chloramphenicol acetyltransferase. AB - A novel plasmid was generated which allowed the expression of the cytosolic bacterial enzyme chloramphenicol acetyl transferase (CAT) in COS-7 cells. Upon transfection, the majority of the novel CAT activity was found in the cytosol fraction of COS cells. Chimeric molecules were made between N-terminal portions of the type IVA cyclic AMP-specific rat 'dunce-like' phosphodiesterase (RD1) (RNPDE4A1A; rPDE-IVA1) fused to CAT at its N-terminus. Expression in COS-7 cells of chimeras formed from 1-100RD1-CAT and 1-25RD1-CAT now showed CAT activity associated with the membrane fraction. In contrast, a chimera formed from 26 100RD1-CAT showed an identical expression pattern to native CAT, with the major fraction of CAT activity occurring in the cytosol fraction. Membrane-bound CAT activity provided by 1-100RD1-CAT and 1-25RD1-CAT was not released by either high salt or washing treatments but was solubilized in a dose-dependent fashion by the non-ionic detergent Triton X-100. Subcellular fractionation of COS-7 cells showed that, as with RD1, the membrane-bound activity of the RD1-CAT chimera followed that of the plasma membrane marker 5'-nucleotidase. Plasmids containing chimeric cDNAs were exposed to a coupled transcription-translation system that, in addition to the full-length chimeras, was found to generate a range of N-terminal truncated species due to initiation at different methionine residues. Incubation of the mature protein products formed in this system with a COS cell membrane fraction showed that only those chimeric CAT constructs containing the first 25 amino acids of RD1 became membrane-associated. The unique 25 amino acid N terminal domain of RD1 contains structural information that can confer membrane association upon an essentially soluble protein. PMID- 7772059 TI - Insulin inhibits the phosphorylation of alpha-Gi-2 in intact hepatocytes. AB - Challenge of intact hepatocytes with insulin reduced the level of phosphorylated alpha-Gi-2 found under basal (resting) conditions. At maximally effective concentrations of insulin the steady-state labelling of alpha-Gi-2 was reduced by approximately 21%. Insulin achieved this in a time- and dose-dependent fashion, exhibiting an IC50 value of 109 +/- 22 pM. The increased labelling of alpha-Gi-2 seen after challenge of cells with phorbol 12-myristate 13-acetate was also attenuated by insulin. Treatment of hepatocytes with the protein phosphatase inhibitor okadaic acid increased the labelling of alpha-Gi-2 in a fashion which was insensitive to the action of insulin. It is suggested that insulin may reduce the level of phosphorylation of alpha-Gi-2 by stimulating intracellular protein phosphatase activity and that this action may offer a molecular explanation for the ability of insulin to inhibit adenylate cyclase activity in hepatocytes by increasing the level of non-phosphorylated alpha-Gi-2. PMID- 7772060 TI - Radiolabeled cholesteryl ethers trace LDL cholesteryl esters but not HDL cholesteryl esters in the rat. AB - The intravascular metabolism of cholesteryl [1-14C]oleoyl ester and [1,2 3H(N)]cholesteryl palmityl ether was compared in the rat, an animal species without plasma cholesteryl ester transfer activity (CETA). The tracers had identical plasma disappearance rates when they were incorporated into human or rat low density lipoproteins (LDL). Fractional catabolic rates (FCR) were 0.081 +/- 0.014 h-1 and 0.080 +/- 0.013 h-1 for human LDL ester and ether and 0.098 +/- 0.007 h-1 and 0.101 +/- 0.007 h-1 for rat LDL ester and ether, respectively. In contrast, the ether had plasma disappearance rates that were 24%-25% lower than the ester when they were incorporated into human or rat high density lipoproteins (HDL). FCR were 0.230 +/- 0.020 and 0.173 +/- 0.030 h-1 for human HDL ester and ether and 0.131 +/- 0.020 h-1 and 0.100 +/- 0.017 h-1 for rat HDL ester and ether respectively. Biological screening of the rat HDL preparations did not affect these differences. The results of these studies indicate that in the absence of plasma CETA, cholesteryl ethers can be used to trace LDL cholesteryl esters but not to trace HDL cholesteryl esters. PMID- 7772058 TI - Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected]. AB - We have isolated from a human T-cell Jurkat cDNA library a novel human cDNA (2EL) that is closely related to the human type-IV PDE splice variant family 'A' (PDE IVA) cDNA characterized previously by us [Sullivan, Egerton, Shakur, Marquardsen and Houslay (1994) Cell. Signalling 6, 793-812]; (h6.1, PDE-IVA/h6.1; HSPDE4A7). (PDE stands for cyclic nucleotide phosphodiesterase). The novel cDNA 2EL (PDE IVA/2EL; HSPDE4A8) contains two regions of unique sequence not found in PDE IVA/h6.1. These are a distinct 5'-end and a 34 bp insert which occurs within a domain thought to encode the type-IV PDE catalytic site and which can be expected to result in premature truncation of any expressed protein. HSPDE4A8 appeared to be catalytically inactive. Isolation and characterization of a human genomic cosmid clone revealed that 2EL and h6.1 represent alternative splice variants of the human PDE-IVA gene. Using a unique sequence found at the 5'-end of the 2EL cDNA, a probe was generated which was used to screen the DNA of human-hamster hybrids. This located the human gene for PDE-IVA to human chromosome 19. Through both the analysis of genomic DNAs from a human-hamster somatic cell hybrid panel and also using fluorescent in situ hybridization, it was shown that the human PDE IVA gene is located on human chromosome 19, between p13.2 [corrected] and q12. This region on chromosome 19 has been shown to be related to genetic diseases such as the autosomal dominant cerebrovascular disease CADASIL, susceptibility to late-onset Alzheimer's disease and changes seen in benign pituitary and thyroid adenomas. PMID- 7772061 TI - Intimal thickenings of human aorta contain modified reassembled lipoproteins. AB - The aim of this study was to determine whether in human aortas early minute changes such as minimal intimal thickenings (MIT), developed in areas known to have a predilection to atherosclerosis, contain modified reassembled lipoproteins (MRLp) such as extracellular liposomes (EL) and lipid droplets (LD). These features have been previously detected in the aortic lesion-prone areas of rabbits and hamsters fed a fat-rich diet. Tissue samples of the aortic arch and thoracic aorta from 12 young subjects who died in accidents were selectively collected from grossly normal regions. By light microscopy, some of these regions were found to contain MIT. The normal areas and the MIT were separately examined by electron microscopy or subjected to fractionation and partial biochemical characterization. The MIT (approximately 25-100 microns thick) were constituted by a pronounced proliferation of extracellular matrix, especially elastin and microfibrils, with interspersed lipid deposits appearing as EL and LD. Commonly, MIT did not contain smooth muscle cells, macrophages, foam cells or cytolytic debris. Such components were only occasionally found in specimens excised from the vicinity of fatty streaks. Saline extracts of MIT or grossly normal aortic regions were subjected to a four-step purification procedure consisting of gel filtration, affinity chromatography on anti-apo B and anti-albumin Sepharose, followed by density gradient ultracentrifugation. The entire procedure was monitored by negative staining, lipid assays, SDS PAGE and immunoblotting. From the initial MRLp mixture, two fractions were obtained: fraction 1 containing multilamellar EL and LD, and fraction 2 composed mostly of unilamellar EL. As compared with serum LDL, the cholesteryl ester/unesterified cholesterol ratio was 4-6-fold lower in fraction 1 and 15-19-fold lower in fraction 2. On SDS-PAGE the fraction 2 displayed a single protein band of 66 kDa, immunochemically identified as albumin. The MRLp isolated from human aortas with minimal intimal thickenings appeared to be similar to those purified from the prelesional stage aorta of hyperlipidemic rabbits and hamsters. PMID- 7772062 TI - Spontaneous platelet aggregation in whole blood is increased in non-insulin dependent diabetes mellitus and in female but not male patients with primary dyslipidemia. AB - Increased platelet aggregability has been shown in hypercholesterolemia, and stirring-induced spontaneous aggregation in whole blood is increased in insulin dependent diabetes mellitus (DM). We have determined spontaneous aggregation in citrated (10 mM) whole blood, from 27 primary dyslipidemic patients (DYS; 14F, 13M), 16 male non-insulin-dependent DM (NIDDM) patients, and 17 normolipidemic controls (N; 6F, 11M), using platelet counting to quantify aggregation. Spontaneous aggregation was significantly higher, both in the female DYS group (median 30% [interquartile range 25,50], P < 0.005) and the NIDDM group (33% [25,41], P < 0.005), than in the N group (17% [12,27]), but did not differ significantly in the male DYS group (23% [10,33]). Similar results were obtained in the presence of indomethacin (25 mumol/l) to prevent artefactual thromboxane (TX) A2 formation, indicating that increased spontaneous aggregation was TXA2 independent. Interestingly, increased spontaneous aggregation appeared to be independent of serum cholesterol and triglyceride concentrations, as well as age and sex per se. We conclude that spontaneous platelet aggregation was increased both in female primary dyslipidemic patients and NIDDM patients, but not in male DYS patients. The clinical significance of increased spontaneous platelet aggregability is that it may favour shear-induced aggregation which may occur at critical arterial stenoses in vivo leading to thrombus formation. PMID- 7772063 TI - Identification of a new apolipoprotein E variant (E2 Arg142-->Leu) in type III hyperlipidemia. AB - A new rare apolipoprotein E mutant was identified as we were investigating the apolipoprotein E genotype of patients with type III hyperlipidemia (HLP III). The unusual DNA restriction fragment length polymorphism profile and then the sequence analysis of a PCR amplified fragment of the proband's apo E gene revealed a simple base substitution (G-->T) at nucleotide 3836. This mutation leads to the replacement of arginine by leucine at position 142 of the mature protein. The proband carried the mutant allele at the heterozygous status with an epsilon 3 allele. Subsequently, analysis of the proband's father's apo E gene showed that same mutated allele associated with an epsilon 2 allele. The two subjects presented a dysbetalipoproteinemia in which this new apo E variant could be implicated. PMID- 7772064 TI - Distribution, fatty acid composition and apolipoprotein A-I immunoreactivity of high density lipoprotein subfractions in myocardial infarction. AB - The lipoprotein profile, the HDL subfractions and the apolipoprotein (apo) A-I conformation of HDL were determined in 119 patients with myocardial infarction and 119 controls, paired for age. Apo A-I conformation was assessed by its immunoreactivity towards two monoclonal antibodies, 5F6 and 3G10. HDL phospholipid levels and fatty acid composition were also determined. HDL and HDL3 cholesterol, apo A-I, LpA-I and LpA-I:A-II levels were significantly lower in patients than in controls, whereas the levels of total and LDL-cholesterol and of apo B were not different. Apo A-I immunoreactivity against MAb 5F6 was significantly better in patients than in controls, while the immunoreactivity against 3G10 was similar. Paired stepwise logistic regression showed only apo A I, HDL3 cholesterol and 5F6 immunoreactivity to be significantly related to myocardial infarction. After adjustment for HDL cholesterol, lower levels of HDL phospholipids and polyunsaturated fatty acids (PUFA) were found in patients compared with controls. Hence, of all HDL markers, apo A-I and HDL3 cholesterol appear to be the most informative. Also, lower HDL phospholipid and PUFA content may explain a different apo A-I conformation in patients with myocardial infarction. PMID- 7772065 TI - Quantitation of the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta with dystrophic calcification. AB - Pyridinoline and, its minor analogue deoxypyridinoline, are trifunctional crosslinks of mature collagen in the connective tissues. Pentosidine, a new type of fluorescent crosslink, is possibly one of the senescent crosslinks but its function and metabolism are still unclear. In this study, we quantitated the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta which were obtained from 21 autopsy cases. In each case, the existence of dystrophic calcification in the aorta and complications (diabetes, chronic renal failure and hypertension) were examined. The determination of the content of the three crosslinks was carried out using high performance liquid chromatography (HPLC) analysis. In calcified lesions, the amount of deoxypyridinoline/collagen showed a decrease and the amount of deoxypyridinoline/pyridinoline showed a prominent decrease compared to those in non-calcified lesions (deoxypyridinoline/collagen, P < 0.005; deoxypyridinoline/pyridinoline, P < 0.0001). In non-calcified lesions without complications, the amount of pentosidine/pyridinoline and that of pentosidine/deoxypyridinoline significantly increased with age (pentosidine/pyridinoline, r = 0.704, P < 0.05; pentosidine/deoxypyridinoline, r = 0.624, P < 0.05). This result suggests a possible relationship between dystrophic calcification and crosslink formation of collagen in human aorta. PMID- 7772066 TI - The ansamycins: a novel class of hypolipidemic agents with a high affinity for lipoproteins. AB - The ansamycins are derivatives of 3-piperazino rifamycin with potent hypolipidemic activity in nonprimate and primate species. Since the cholesterol reduction results from increased uptake and catabolism of lipoprotein cholesterol, it was hypothesized that the hydrophobicity of the ansamycins could result in a lipoprotein association which facilitates clearance. When radiolabeled ansamycins CGP 43371 or CGS 24565 were incubated with human plasma, > 95% was lipoprotein-bound up to drug levels of 25 microM. With plasma from chow fed rats, radiolabeled compounds again distributed with the lipoproteins. Feeding a cholesterol/cholic acid diet to rats shifted the cholesterol distribution to lower density lipoproteins and in vitro incubation resulted in a shift of radiolabeled drug to lower density lipoproteins as well. Intravenous administration of radiolabeled ansamycins to chow-fed or cholesterol-fed rats resulted in a plasma lipoprotein binding profile indistinguishable from the corresponding in vitro incubations. When [14C]-CGP 43371 bound in vitro to high density lipoprotein (HDL) was reincubated with increasing concentrations of low density lipoprotein (LDL), a concentration-dependent fall in HDL association and increase in LDL binding was observed. Thus, the ansamycins have a high affinity for all plasma lipoproteins and can transfer between lipoprotein fractions. When [125I]-labeled LDL or HDL was incubated with CGP 43371 and Hep G2 cells, the cell association of the 125I label was significantly increased in a dose-dependent manner. In addition, plasma clearance of [14C]cholesterol oleate-labeled HDL coinjected with CGP 43371 was accelerated relative to control rats and radioactivity was specifically increased in livers of CGP 43371-treated rats. The physical association of the ansamycins with lipoproteins may thus lead to subtle conformational changes and enhanced hepatic uptake. PMID- 7772067 TI - Similar to oleic acid, eicosapentaenoic acid stimulates apolipoprotein B secretion by inhibiting its intracellular degradation in Hep G2 cells. AB - We previously reported that oleic acid (OA) rapidly increased apolipoprotein (apo) B secretion by suppressing early intracellular degradation of nascent apo B in Hep G2 cells and suggested that the suppression of apo B degradation is associated with triglyceride (TG) biosynthesis from OA. To determine whether the inhibition of apo B degradation is associated with increased TG synthesis or is a direct effect of OA, we examined the effect of another fatty acid, eicosapentoenoic acid (EPA), on apo B kinetics in Hep G2 cells, since it is well known to have hypolipidemic action in clinical studies. The incorporation of [3H]glycerol into cellular TG was stimulated five-fold when Hep G2 cells were incubated for 2 h with EPA or OA (0.4 or 0.8 mM-1.5% bovine serum albumin (BSA) complex). The incorporation of [14C]acetic acid into cellular cholesteryl ester (CE) was significantly decreased by EPA treatment, whereas OA did not affect CE synthesis. Similar effects of these fatty acids on cellular lipid synthesis were observed in long-term incubation (24 h). Apo B was linearly secreted into the medium during 3 h, and EPA and OA doubled the rate of secretion. In long-term (24 h) incubations, both fatty acids significantly increased the incorporation of [3H]leucine into secreted apo B radioactivity or the accumulation of apo B mass in the medium. Pulse-chase studies revealed that both EPA and OA reduced intracellular apo B degradation to a similar degree. The inhibition of apo B degradation was also observed when the cells were preincubated with either EPA or OA for 24 h. These results suggest that increased TG synthesis leads to suppression of intracellular apo B degradation, which is independent of the source of exogenous fatty acid. PMID- 7772069 TI - Acyl-coenzyme A:cholesterol-acyltransferase (ACAT) inhibitors modulate monocyte adhesion to aortic endothelial cells. AB - Increased monocyte adhesion to aortic endothelium is observed in the pathogenesis of atherosclerosis. The role of endothelial acyl-coenzyme A:cholesterol acyltransferase (ACAT) in the regulation of monocyte adhesion is not known. To examine the potential role of this enzyme in monocyte adhesion, a specific ACAT inhibitor, CI-976, was utilized. Although the basal adhesion of U937 monocytic cells to porcine aortic endothelial cells was low, treatment of the endothelial cells with lipopolysaccharide (LPS) markedly increased monocyte adhesion. Monocyte adhesion to LPS-treated endothelial cells was markedly inhibited by CI 976 treatment of the endothelial cells. Similarly, another ACAT inhibitor, PD 132301-2, whose structure is distinct from CI-976, also decreased monocyte adhesion. CI-976 treatment of endothelial cells also decreased endothelial cell ACAT activity. Since leukotriene B4 (LTB4) is known to promote leukocyte endothelial cell adhesion, endothelial cell production of this leukotriene was examined after incubation with CI-976. CI-976 treatment markedly decreased LTB4 synthesis. Exogenous LTB4 addition to CI-976 treated cells reversed the effects of this compound on monocyte adhesion. These data demonstrate that ACAT inhibitors decrease monocyte adhesion to endothelial cells. Similar mechanisms may contribute to antiatherosclerotic effects of ACAT inhibitors in vivo. PMID- 7772068 TI - Lysophosphatidylcholine causes Ca2+ influx, enhanced DNA synthesis and cytotoxicity in cultured vascular smooth muscle cells. AB - The effects of lysophosphatidylcholine (LPC), a vasoactive phospholipid, on intracellular free calcium concentration ([Ca2+]i), DNA synthesis and cytotoxicity of vascular smooth muscle cells (VSMC) were studied. LPC from 10(-7) to 10(-5) mol/l dose-dependently induced a sustained increase in [Ca2+]i. In contrast to the response of [Ca2+]i induced by angiotensin II, that induced by LPC was totally abolished when extracellular Ca2+ was removed, was not affected by pretreatment of the cells with islet-activating protein, and was not desensitized by repeated addition. 8-(N,N-Diethylamino)octyl 3,4,5 trimethoxybenzoic acid (TMB-8), an inhibitor of Ca2+ release from intracellular Ca2+ stores, 1-(5-isoquinolinesulfonyl)-2-methylpiperadine dihydrochloride (H-7), an inhibitor of protein kinase C, KT5823, an inhibitor of protein kinase G, and Ca2+ channel blockers failed to suppress the LPC-induced increase in [Ca2+]i. LPC at 10(-5) mol/l caused significant stimulation of [3H]thymidine incorporation into VSMC, and at concentrations of 10(-5) mol/l and higher dose-dependently stimulated release of lactate dehydrogenase in cell culture supernatants. Moreover, digitonin mimicked the effects of LPC on [Ca2+]i, and also caused similar effects to those of LPC on DNA synthesis and cytotoxicity in VSMC. These observations suggest that LPC causes both cell growth and cell injury of VSMC, at least partly, through its detergent action, causing membrane leakiness and resultant [Ca2+]i overload in vitro, thus indicating the possible participation of LPC in atherosclerosis and/or injury of the vascular wall. PMID- 7772070 TI - Oxidisability of low density lipoproteins in patients with carotid or femoral artery atherosclerosis. AB - Oxidation of low density lipoprotein (LDL) is implicated in the pathogenesis of atherosclerosis. In this study the susceptibility to oxidation of LDL (from patients with atherosclerosis) is related to the progression of the disease. LDL were isolated from 37 patients with demonstrable atherosclerotic plaques. The susceptibility of LDL to oxidation (induced by an exogenous oxidative stress) was assessed by measuring the breakdown products of lipid peroxidation, the increased formation of conjugated dienes, and changes in surface charge of the apolipoprotein B (apo B). Progression of the atherosclerotic plaque was assessed by measuring the maximum velocity of blood through the narrowest portion of the vessel at inclusion and after one year. Twenty-nine of the 37 samples taken were found to have LDL that were partially oxidised, whereas 8 samples showed LDL whose state of oxidation was within the normal range. Progression of the atherosclerotic plaque occurred in 19 (66%) of the 29 patients whose lipoproteins were partially oxidised compared with only 2 (25%) of the 8 patients with normal lipoproteins (P = 0.055, Fisher's exact test). These data support an association between the progression of atherosclerotic plaques in carotid and femoral vessels and the susceptibility to oxidation of LDL. PMID- 7772071 TI - Arginine residues at codons 112 and 158 in the apolipoprotein E gene correspond to the ancestral state in humans. AB - Apolipoprotein E is a secretory glycoprotein that associates with lipoprotein particles and is coded for by a single locus on chromosome 19. The three common allelic isoforms of this protein (apo E2, apo E3 and apo E4) are associated with distinct patterns of lipoprotein metabolism and variable risks for coronary artery disease. In addition, recent work has shown that the presence of the apo E4 isoform constitutes a major risk for developing late-onset Alzheimer's disease as well as hypercholesterolaemia. The only differences between these isoforms result from cysteine-arginine interchanges at codons 112 and 158. There is considerable disagreement in the literature concerning the identity of the ancestral allele. In order to resolve this, 24 chimpanzees and individuals from a number of other primate species were analysed. All were similar to apo E4. This suggests that apo E4 is the ancestral allele and that apo E2 and apo E3 arose after the split of the human and chimpanzee lineages. PMID- 7772072 TI - Vitamins E, C and lipid peroxidation in plasma and arterial tissue of smokers and non-smokers. AB - An imbalance between pro-oxidants and antioxidants is operative in atherosclerosis. Cigarette smoke is a major risk factor of atherosclerosis and has been reported to contain large amounts of oxidants. We assessed arterial (internal mammary artery) and plasma levels of vitamins E and C and lipid peroxides in 48 male patients, 24 smokers and 24 non-smokers, undergoing coronary bypass surgery. Lipid peroxidation was studied using fluorescent products of lipid peroxidation (FPLs). Tissue vitamins E and C levels were significantly lower and FPLs significantly higher in smokers than in non-smokers (P < 0.0006, 0.0005 and 0.0005, respectively). This pattern was associated with lower vitamin C and higher lipid peroxide plasma levels in smokers than in non-smokers (P < 0.0002 and 0.0005, respectively). Vitamins E and C plasma levels were strongly related to their tissue content both in smokers (r = 0.60, P < 0.005 and r = 0.57, P < 0.01) and in non-smokers (r = 0.42, P < 0.05 and r = 0.46, P < 0.05). Moreover, vitamin E content was significantly related to that of vitamin C only in the arterial tissue of both groups, pointing to the existence of a functional interaction between these antioxidants. In both groups, FPLs were significantly and inversely related to vitamin C in plasma and to vitamin E in tissue, suggesting the antioxidant primary of vitamin C and vitamin E in the plasma and arterial tissue compartments, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772073 TI - Metabolism of modified LDL by cultured human placental cells. AB - All major classes of normal circulating lipoproteins can be metabolized by human placental cells. However, the metabolism of abnormal or modified lipoproteins has been little studied. We therefore investigated whether placental cells metabolize acetylated low density lipoprotein (ac-LDL) or oxidatively-modified LDL (ox-LDL), both of which are metabolized by scavenger receptors, and if so, whether modified LDL stimulates progesterone secretion as does normal LDL. Placental macrophages and trophoblasts were isolated on a 40% Percoll gradient after enzymatic digestion. The cellular uptake and degradation of [125I]-ac-LDL was 20-fold higher than [125I]-LDL in both macrophages and trophoblasts. Both cell types demonstrated high affinity and saturable degradation. Similarly, increased esterification of [14C]-labelled oleic acid to cholesterol was observed when cells were incubated with ac-LDL vs. LDL. Uptake of ac-LDL by trophoblasts also was demonstrated by colocalization of fluorescently labelled ac-LDL and fluorescent antibodies specific for trophoblasts. Similar colocalization of fluorescent ac-LDL and fluorescent anti-macrophage specific epitopes was seen in macrophages. Uptake and degradation of [125I]-ac-LDL by placental cells was inhibited by increasing concentrations of unlabelled ac-LDL or fucoidin but not LDL, indicating uptake by a scavenger receptor. Both unlabelled ac-LDL and ox-LDL inhibited uptake of [125I]-labelled ox-LDL, suggesting uptake by a common mechanism. Although secretion of progesterone by trophoblasts was stimulated by incubation with LDL, progesterone secretion by trophoblasts was not stimulated by ac-LDL and only minimally stimulated by ox-LDL. CONCLUSIONS: Scavenger receptors are present in human placental trophoblasts as well as macrophages. Scavenger receptor activity greatly exceeds that of LDL receptor activity in both cell types. However, cholesterol assimilated via the scavenger receptor pathway appears to be disconnected from endocrine steroidogenesis in trophoblasts. Thus, we hypothesize that scavenger receptors function in trophoblasts to degrade modified lipoproteins and prevent toxic effects on placental cellular function and fetal growth and development. PMID- 7772074 TI - A deletion polymorphism in the angiotensin converting enzyme gene is not associated with coronary heart disease in an Austrian population. AB - This study examined a possible relationship between genetic variation in the gene coding for the angiotensin converting enzyme (ACE) and increased risk for coronary heart disease (CHD) in an Austrian population. Polymerase chain reaction (PCR) was used to determine the genotypes for an insertion/deletion polymorphism in intron 16 of the ACE gene in 315 patients with CHD and in 149 normal controls. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The genotype distribution among our patients was not significantly different from that among controls. We were not able to show a significant association of the DD genotype with coronary heart disease in subgroups containing patients considered at low coronary risk. There was no association of lipid parameters and ACE genotype. From these data we conclude that, in the Austrian population, the insertion/deletion polymorphism in the ACE gene cannot be used as a marker for coronary risk assessment. PMID- 7772075 TI - The relationship of APOE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado. AB - We have determined apolipoprotein E (apoE = protein, APOE = gene) polymorphism and its relationship with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels in normoglycemic Hispanics (n = 446) and non-Hispanic whites (NHWs) (n = 659) as well as in diabetic Hispanics (n = 235) and NHWs (n = 116) from the San Luis Valley, Colorado. Effects were estimated separately for each group, and within each group men and women were analyzed separately; women were further categorized into pre- and post-menopausal status. The distribution of the APOE genotype pattern was comparable between the NHW normoglycemics and diabetics but it was significantly different among Hispanic normoglycemics and diabetics (P < 0.005). In the normoglycemic sample the APOE allele frequencies were significantly different between the two ethnic groups: the APOE*2 (0.09 vs. 0.05; P < 0.01) and APOE*4 (0.15 vs. 0.09; P < 0.002) allele frequencies were higher while the APOE*3 (0.76 vs. 0.86; P < 0.0001) allele frequency was lower in NHWs than in Hispanics. Significant variability among the three common APOE genotypes (3-2, 3-3, and 4-3) was observed for TC and LDL-C in normoglycemic Hispanic women (P = 0.09 and P = 0.03) but not in Hispanic men. In normoglycemic NHWs, however, significant mean differences among APOE genotypes were observed for TC and LDL-C in both women (P < 0.0001 and P < 0.0001) and men (P = 0.009 and P = 0.01). In Hispanic females, the APOE polymorphism accounted for 5.6% and 7.6% of the phenotypic variance for TC and LDL-C, respectively. In NHW females, the APOE polymorphism explained 10.2% of the phenotypic variance for TC and LDL-C, and in NHW males these values were 6.2% and 7.5%, respectively. There was no evidence of physiologic interaction between the APOE polymorphism and menopause status in affecting TC and LDL-C in NHW women (P = 0.65 and P = 0.55) but a suggestion of interaction was observed in Hispanic women for TC and LDL-C (P = 0.11 and 0.07). After the Hispanic women were stratified into pre- and postmenopausal groups, the effect of the APOE polymorphism on TC and LDL-C was significant only in the premenopausal group. Among diabetics, no significant effect of the APOE polymorphism was seen on cholesterol levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772077 TI - Cigarette smoke extract inhibits oxidative modification of low density lipoprotein. AB - Oxidative modification of low density lipoprotein (LDL) by cigarette smoke has been suggested in several recent studies. To characterize possible modification of LDL by cigarette smoke extract (CSE), we incubated LDL with CSE either in the presence or absence of the chemical pro-oxidants, cupric chloride or 2,2'-azo bis(2-amidinopropane) hydrochloride (AAPH). Surprisingly, CSE inhibited oxidative modification of LDL induced by either copper or AAPH. Under such oxidant stress conditions, CSE inhibited formation of thiobarbituric acid-reactive substances and also inhibited the increased agarose gel electrophoretic mobility of LDL in a dose-response manner. In addition, CSE prevented degradation of phosphatidylcholine to lysophosphatidylcholine and also fragmentation of the apolipoprotein B-100 moiety of LDL. Finally, CSE inhibited loss of immunoreactivity of the treated LDL with a murine monoclonal antibody against human apolipoprotein B-100. On the other hand, at higher concentrations, CSE per se was still able to cause structural changes in LDL. After incubation with CSE for 24 h, LDL showed a slight increase in agarose gel electrophoretic mobility, a slight loss of immunoreactivity with monoclonal antibody, and a marked increase in protein carbonyl formation. Lipid peroxidation did not appear to be involved in the modification of LDL caused by CSE. It is suggested that reactive aldehydes present in cigarette smoke may cause direct chemical modification of LDL. Furthermore, the free radical-scavenging potential of the tar fraction of cigarette smoke may be responsible for the apparent antioxidant properties of CSE against LDL oxidation. PMID- 7772076 TI - High density lipoprotein metabolism is altered by dietary cholesterol but not fat saturation in guinea pigs. AB - To study dietary fat and cholesterol effects on plasma high density lipoprotein (HDL) metabolism and rates of apolipoprotein (apo) A-I catabolism, guinea pigs were fed 15% (wt/wt) lard- or corn oil-based diets with 0.01% (basal), 0.08%, 0.17% or 0.33% cholesterol. Absorbed dietary cholesterol provided 6%, 50%, 100% and 200%, respectively, of the daily endogenous cholesterol synthetic mass. While total plasma cholesterol concentrations increased significantly above basal levels at the 0.17% and 0.33% cholesterol intakes, plasma apo E-free HDL (EoHDL) cholesterol concentrations did not increase significantly until the 0.33% cholesterol level (P < 0.001). Fractional catabolic rates (FCR) of injected [131I]-apo A-I were not altered by dietary treatment, either fat saturation or cholesterol, but were inversely correlated with plasma EoHDL cholesterol levels (r = -0.622), suggestive of a regulatory role of turnover rates on HDL cholesterol levels independent of dietary treatment. Analysis of the high affinity EoHDL binding to isolated hepatic membranes suggested that hepatic binding was not a determinant of HDL catabolism, as dietary cholesterol-induced decreases in Bmax (binding capacity) were not correlated with changes in apo A-I FCR. Even though dietary cholesterol was associated with increased plasma EoHDL cholesterol and with decreased HDL binding protein Bmax, these values did not correlate with each other nor with effects on apo A-I FCR. PMID- 7772078 TI - Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. AB - The inhibition of low density lipoprotein (LDL) oxidation has been postulated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Available data on the ability of beta-carotene to inhibit LDL oxidation are conflicting. We examined the role of in vivo and in vitro supplementation with beta-carotene on metal ion-dependent (cupric ions, Cu2+) and metal ion-independent (2,2'-azobis[2-amidinopropane]dihydrochloride, AAPH) oxidation of LDL as measured by the formation of conjugated dienes (absorbance at 234 nm). Sixteen subjects were supplemented with 50-100 mg of beta-carotene on alternate days for 3 weeks following a week-long loading dose of 100 mg/day. Plasma beta-carotene levels rose 5.5-fold, while LDL beta-carotene levels rose 8.5-fold. Oxidation of LDL by Cu2+ or AAPH was not significantly delayed after in vivo supplementation with beta-carotene compared with baseline. For AAPH, the lag phase (in minutes) was 75 +/- 8 at baseline and 83 +/- 14 after supplementation (P = 0.07). For Cu2+, the lag phase was 172 +/- 41 at baseline and decreased to 130 +/- 24 after supplementation (P < 0.01). Similarly, no protective effect against Cu(2+)-induced oxidation was observed when beta-carotene was added to LDL in vitro. Supplementation of plasma with beta-carotene in vitro prior to LDL isolation also did not enhance LDL's resistance to Cu(2+)- or AAPH-induced oxidation, despite a 5-fold increase in LDL beta-carotene levels over vehicle control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772079 TI - Identification of a variant collagen alpha 3 (VI) in early-stage avian arteriosclerotic plaques. AB - A 170 kD protein, prominent in soluble extracts of rooster arteriosclerotic plaques, has been partially characterized. The protein was eluted from a size exclusion column in a broad molecular weight fraction > 100 kD. Concanavalin A and a murine polyclonal antibody raised against the isolated 170 kD protein reacted with the protein on Western blots. The 170 kD protein had an isoelectric point of approximately 5.4 and was digested by collagenase treatment. Amino acid analysis of a 70 kD fragment of the protein closely resembled that for chick collagen alpha 3 (VI). A 13 amino acid sequence within this 70 kD fragment had 69% identity and 85% homology to chicken collagen alpha 3 (VI). Soluble protein extracts from cultured plaque smooth muscle cells (SMC), and from healthy artery SMC, contained low levels of the protein. These cellular extracts also reacted with the polyclonal antibody described above. Although the protein lacks absolute amino acid sequence identity with collagen alpha 3 (VI) it shares with it many biochemical features, suggesting that the 170 kD protein is a variant species of chick collagen alpha 3 (VI). PMID- 7772080 TI - Inverse relationship between cardiorespiratory fitness and carotid atherosclerosis. AB - The association between cardiorespiratory fitness (VO2max) and carotid atherosclerosis was analyzed in 163 men, aged 50 to 60 years. VO2max was assessed using breath-by-breath respiratory gas analyses during maximal exercise stress test. Atherosclerosis was evaluated quantitatively as intima-media thickness (IMT) of the right and left carotid arteries by high-resolution B-mode ultrasonography. Mean VO2max was 29.6 ml/kg per min (95%CI 28.7;30.5), common carotid IMT 1.04 mm (95%CI 1.01;1.07) and carotid bifurcation IMT 1.73 mm (95%CI 1.66;1.81). VO2max correlated inversely with carotid bifurcation IMT (r = -0.31, P < 0.001), but not with common carotid IMT (r = -0.13, P = 0.102). Men in the highest quartile of VO2max had lower (P < 0.001) bifurcation IMT 1.51 mm (95%CI 1.41;1.61) than men in the lowest (1.95 mm (95%CI 1.75;2.16)) and in the second lowest VO2max quartile (1.79 mm (1.63; 1.95)). The difference persisted (P = 0.014) after controlling for age, LDL-cholesterol, systolic blood pressure, saturated fat intake, current health status and exercise-induced ST-segment depression. These data suggest that cardiorespiratory fitness is an important independent predictor of carotid atherosclerosis in middle-aged men. PMID- 7772081 TI - The effects of colestipol tablets compared with colestipol granules on plasma cholesterol and other lipids in moderately hypercholesterolemic patients. AB - The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study. Three hundred and seventeen patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and had low-density lipoprotein cholesterol (LDL-C) levels > or = 4.14 mmol/l (160 mg/dl) and < or = 6.46 mmol/l (250 mg/dl) were studied. Study medication was taken twice a day, with breakfast and supper, for 8 weeks. The six parallel treatment groups consisted of colestipol tablets 2 g b.i.d. and 8 g b.i.d., matching placebo tablets b.i.d., colestipol granules 2 g b.i.d. and 8 g b.i.d., and matching placebo granules b.i.d.. Study endpoints included absolute change and percentage change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C lowering was the primary efficacy endpoint. Treatment with colestipol tablets and colestipol granules resulted in virtually identical, statistically significant (P < or = 0.05) reductions of LDL-C, total cholesterol (TC), TC/HDL-C, and apolipoprotein B (apo B). Compared with placebo, all active treatments (tablets 4 g/day, tablets 16 g/day, granules 4 g/day, granules 16 g/day) significantly reduced LDL-C (12%, 24%, 12%, 25%, respectively), TC (7%, 15%, 8%, 15%, respectively), TC/HDL-C (8%, 14%, 9%, 15%, respectively) and apo B (12%, 20%, 13%, 22%, respectively). All active treatments significantly increased lipoprotein particle AI (LpAI) (5%, 23%, 14%, 18%, respectively). VLDL-C and triglycerides increased significantly in the high-dose groups. The proportions of patients reporting adverse events, largely gastrointestinal-related, were not different among the active treatment groups. The treatments were well-tolerated, and no drug-related serious adverse events were reported. Patients experienced with granule medication prior to this study preferred tablets over granules. This study demonstrates that colestipol tablets are an effective treatment to reduce LDL-C in patients with primary hypercholesterolemia, are equivalent to colestipol granules, are well-tolerated, and are preferred over granules by patients. PMID- 7772082 TI - Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding. AB - Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum cholesterol) and apo E-deficient mice on a regular chow diet (20 mM serum cholesterol) did not show such lesions. Also, apo E3-Leiden transgenic mice fed a high fat diet, with 60 mM of serum cholesterol, did not exhibit any xanthomatosis. The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice. We conclude that the lack of apo E results in atypical disseminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of cholesterol deposition. PMID- 7772083 TI - Atherosclerotic risk factors are increased in clinically healthy subjects with microalbuminuria. AB - Increased morbidity and mortality from atherosclerotic vascular disease were observed in subjects with slightly elevated urinary albumin excretion rate (UAER), known as microalbuminuria. Therefore, the association between microalbuminuria and established atherogenic risk factors was studied in clinically healthy subjects. All healthy 40-65 year-old participants with microalbuminuria, examined within the first 21 months of The Copenhagen City Heart Study, were invited, and 28 were studied. An age- and sex-matched group of 60 randomly chosen subjects with normoalbuminuria served as control. Microalbuminuria was defined as a UAER of 6.6-150 micrograms/min, and normoalbuminuria as a UAER < or = 6.6 micrograms/min. In the microalbuminuric group, systolic and diastolic blood pressures were both elevated (mean (95% C.I.) 128 (123-134) vs. 119 (116-122) mmHg; P = 0.005, and 75 (71-78) vs. 69 (67-71) mmHg; P = 0.008, respectively), and serum apolipoprotein (apo) A-1 concentration was lower (1.30 (1.20-1.37) vs. 1.42 (1.36-1.47) milligrams; P = 0.02) in comparison with the normoalbuminuric group. Furthermore, serum HDL-cholesterol concentration tended to be lower, whereas body weight, body mass index and fasting serum insulin concentration were slightly elevated in the microalbuminuric group but not statistically significant. It is concluded that microalbuminuria in clinically healthy subjects is associated with increased levels of atherogenic risk factors. This may contribute to the increased vascular morbidity and mortality observed in these individuals. PMID- 7772085 TI - Rapid development of umbilical metastases after laparoscopic cholecystectomy for unsuspected gallbladder carcinoma. AB - Unsuspected microscopic adenocarcinoma of the gallbladder was identified after operation in a 66-year-old woman undergoing elective laparoscopic cholecystectomy for symptomatic cholelithiasis. An abdominal wall metastasis developed at the periumbilical incision site through which the laparoscope was introduced and through which the gallbladder was removed. A review of the available information on tumor seeding of laparoscopic tracts and drain tracts is presented, as well as implications for the further management of gallbladder cancer and other intraabdominal malignancies. PMID- 7772084 TI - High levels of serum lipoprotein(a) in patients with ischemic heart disease with normal coronary angiogram and thromboangiitis obliterans. AB - To determine whether lipoprotein(a) (Lp(a)) contributes to the acceleration of cardiovascular diseases without atherosclerotic lesion, we have measured serum Lp(a) level in male subjects aged 40-69 years with thromboangiitis obliterans (n = 40) and ischemic heart disease (IHD) with normal coronary angiogram (n = 35) in addition to subjects with arteriosclerosis obliterans (n = 123) and IHD with atherosclerotic coronary lesion (n = 203). Cases who had no IHD, arteriosclerosis obliterans or thromboangiitis obliterans were selected as a control group (n = 316). Subjects without any diseases or abnormal findings in physical examination and laboratory data were selected from the control group as the healthy control group (n = 156). The Lp(a) levels of arteriosclerosis obliterans and IHD with atherosclerotic coronary lesion were significantly higher (17.0 mg/dl and 13.1 mg/dl; median) than those of control and healthy control groups (9.9 mg/dl and 9.4 mg/dl, respectively) (P < 0.01), in agreement with previous reports. Furthermore, the Lp(a) level of IHD with normal coronary angiogram group was significantly higher (18.9 mg/dl) than those of the control and healthy control groups (P < 0.05). The Lp(a) level of thromboangiitis obliterans group was also much higher (21.3 mg/dl) than that of the healthy control group (P < 0.05). The current study suggests that Lp(a) is one of the independent risk factors for the development of atherosclerotic diseases such as arteriosclerosis obliterans and IHD with atherosclerotic coronary lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772086 TI - Psoralen photochemotherapy (PUVA) and pregnancy. AB - BACKGROUND AND DESIGN: Psoralen photochemotherapy (PUVA) may carry a risk of mutagenesis and teratogenesis. Using a medical birth registry and other health registries, infants born to women who had been treated with PUVA were identified. Exposure information was obtained from treating hospitals and from the license granting agency. A total of 504 infants were born of pregnancies occurring after PUVA treatment, and 689 infants were born of pregnancies occurring before such treatment. In another 14 cases, treatment occurred during pregnancy. RESULTS: No increase in infant or child mortality or in the presence of congenital malformations could be seen after PUVA treatment. There was a marked increase in low-birth-weight infants when pregnancy occurred after treatment, and this is probably not explained by maternal smoking, but could be an effect of the underlying disease. CONCLUSIONS: The theoretical mutagenic and teratogenic effect of PUVA treatment apparently does not carry any significant risk for abnormal delivery outcome. PMID- 7772087 TI - Meralgia paresthetica mimicking lumbar radiculopathy. PMID- 7772088 TI - [Diagnosis and therapy of functional dyspepsia]. PMID- 7772090 TI - [Violence. The need for preventive health activity]. PMID- 7772089 TI - [Complications following axillary dissection for breast carcinoma]. AB - Axillary dissection in breast cancer is performed to stage the tumor and to obtain regional tumour control. It is associated with some morbidity. Recently mention was made of post-axillary dissection pain of the arm following damage to one or more of the intercostobrachial nerves. In the University Hospital of Utrecht a radical axillary dissection is routinely performed for breast cancer with transection of the sensory intercostobrachial nerve(s). To evaluate the inherent morbidity of this operation, we interviewed and examined 71 women (75 axillae) who had undergone an axillary dissection for carcinoma of the breast between January 1987 and January 1990. In almost all cases a sensory deficit was present in the axilla and/or arm. In 23 patients (26 sides; 35%) there was pain in the arm, always in the innervation area of the intercostobrachial nerves. One third of these cases had a NRS score of 5 or higher, indicating moderate to severe pain. Seroma and lymphedema were found in 21 patients. In 6 shoulders abduction was reduced to 90 degrees. The several complaints were non-invalidating to 48 patients, slightly invalidating to 13 and moderately invalidating to 10 patients. At present, histological examination of the axillary nodes is still the best way to detect metastases, and it has implications for adjuvant therapies. The results of this study indicate that routinely sacrificing the intercostobrachial nerves during axillary dissection may result in annoying sensory changes and that efforts should be made to preserve one or two of these nerves during the operation. PMID- 7772091 TI - Use of the CORB needle biopsy for the harvesting of iliac crest bone graft. AB - A technique for iliac crest bone grafting has been described which allows rapid harvesting of bone with a significant reduction in the pain, scarring, and distortion traditionally associated with this technique. PMID- 7772092 TI - [Use of alternative medical procedures: between hope and fear]. PMID- 7772093 TI - [Adequate regulation of diabetes mellitus decreases the possibility of diabetic complications]. PMID- 7772094 TI - [Screening for early diagnosis of prostatic cancer]. AB - Early diagnosis is a prerequisite for permanent cure of prostatic carcinoma, and screening of asymptomatic men has been suggested. This proposal is discussed in relation to criteria for meaningful screening, and we conclude that most of these criteria are not fulfilled. While prostatic carcinoma is a major health problem, it has not been proved that early diagnosis and treatment, although undoubtedly useful for some, is profitable for the population as a whole. Many cases of early disease represent latent or slowly growing disease, for whom radical surgery or irradiation, with possible complications, would mean overtreatment. At present, screening cannot be advised for the general population, but should be considered for men at risk because of a history of prostatic cancer among close relatives. PMID- 7772095 TI - Limb-sequencing deficits after left but not right hemisphere damage. AB - The performance of right and left hemisphere stroke patients was compared to normal control groups on a task where subjects alternately hit two targets which varied in size from 0.5 to 6.5 cm. The stroke patients used the arm ipsilateral to damage, and the control groups used the same arm as their respective stroke group. Lesion size and location were similar for the two stroke groups. No deficits were found for the right hemisphere stroke group. The left stroke group's tapping speed was not slower at the smallest target, but became progressively slower relative to the control group's as target size increased. Variability in tapping speed increased as target size increased for all except the left stroke group. While the entire left stroke group was as accurate as their controls, the apraxic, but not nonapraxic, patients made more errors on smaller targets only. Two explanations for these findings both emphasize the left hemisphere's special role in motor programming; one focuses upon its dominance for movements which are independent of sensory feedback and the other emphasizes its specialization for processing rapid temporal information. PMID- 7772096 TI - [Sialidase activity in the cervical connective tissue]. PMID- 7772097 TI - [Folic acid for all women desiring a child: a wrong recommendation]. PMID- 7772098 TI - [Alternative professional practice: a health and jurisprudence consideration]. PMID- 7772099 TI - Can primary care physicians' questions be answered using the medical journal literature? AB - Medical librarians and informatics professionals believe the medical journal literature can be useful in clinical practice, but evidence suggests that practicing physicians do not share this belief. The authors designed a study to determine whether a random sample of "native" questions asked by primary care practitioners could be answered using the journal literature. Participants included forty-nine active, nonacademic primary care physicians providing ambulatory care in rural and nonrural Oregon, and seven medical librarians. The study was conducted in three stages: (1) office interviews with physicians to record clinical questions; (2) online searches to locate answers to selected questions; and (3) clinician feedback regarding the relevance and usefulness of the information retrieved. Of 295 questions recorded during forty-nine interviews, 60 questions were selected at random for searches. The average total time spent searching for and selecting articles for each question was forty-three minutes. The average cost per question searched was $27.37. Clinician feedback was received for 48 of 56 questions (four physicians could not be located, so their questions were not used in tabulating the results). For 28 questions (56%), clinicians judged the material relevant; for 22 questions (46%) the information provided a "clear answer" to their question. They expected the information would have had an impact on their patient in nineteen (40%) cases, and an impact on themselves or their practice in twenty-four (51%) cases. If the results can be generalized, and if the time and cost of performing searches can be reduced, increased use of the journal literature could significantly improve the extent to which primary care physicians' information needs are met. PMID- 7772100 TI - Differences in the treatment of patients with acute myocardial infarction according to patient age. AB - OBJECTIVE: To identify age-related differences in the treatment of patients with acute myocardial infarction. DESIGN: Retrospective cohort study. SETTING: Two university-affiliated medical centers with integrated clinical programs. PATIENTS: 329 patients admitted with acute myocardial infarction in 1988-1990 for whom complete medical records were available. Study exclusions included patients transferred from other hospitals specifically to undergo angiography or other cardiac procedures, nursing home residents, patients with metastatic cancer or dementia, and patients in whom "do not resuscitate" orders were written during the first 2 hospital days. MEASUREMENTS: Medical records were reviewed to determine socio-demographic data, comorbidity, admission severity of illness, medications, the use of specific diagnostic and therapeutic modalities during and after hospitalization, treatment limitations, and patient outcomes. MAIN RESULTS: Chronological age of patients was related to the use of several diagnostic and therapeutic modalities. Using logistic regression to adjust for comorbidity, severity, infarct size and location, and other covariates, patients 75 years and older were 12 times less likely to receive thrombolytic therapy, 8 times less likely to undergo coronary angiography, and 7 times less likely to undergo coronary angioplasty than patients less than 65 years of age. However, age was not related to the use of other modalities, including echocardiography or gated blood pool scanning, pulmonary artery catheterization, and transvenous pacing. Finally, in a logistic regression model, the risk of in-hospital death was 4 times greater for patients 75 years and older than patients less than 65 years. CONCLUSIONS: Physicians' management of patients with acute myocardial infarction differed greatly according to patient age for some diagnostic and therapeutic modalities, but not for others. These findings indicate that generalizations about age-related practice variations should not be based on analysis of a single procedure. Moreover, judgments about the appropriateness of age-related differences in management require knowledge of the relative effectiveness of management strategies in older and younger patients. PMID- 7772101 TI - The risk of ovarian cancer after treatment for infertility. PMID- 7772102 TI - The yield of flexible fiberoptic sigmoidoscopy in the detection of asymptomatic colorectal neoplasia. AB - Recent evidence of a reduction in mortality rates from distal colorectal cancers in populations screened by rigid sigmoidoscopy suggests that further benefits may be achieved by the use of fiberoptic sigmoidoscopy as the screening modality. However, there is limited evidence as to the expected yield of neoplasia using the standard 60-cm instrument. The aim of this study was to determine the yield of neoplasia in an asymptomatic population in the at-risk age group undergoing fiberoptic sigmoidoscopy. Recruitment into the screening program was among State Department personnel. In total, 4,216 asymptomatic subjects (50-65 years) were offered flexible sigmoidoscopic screening performed following a simple enema bowel preparation. Those in whom a neoplastic condition was identified underwent further investigation (colonoscopy or barium enema). Of those offered screening 4,005 (95%) underwent the examination. Eleven carcinomas were detected at flexible sigmoidoscopy and two carcinomas were detected at further investigation in subjects with rectosigmoid polyps. The overall detection rate of carcinomas was 3.2 per 1,000 subjects screened. Histologically proven adenomas were detected in 217 subjects, 5.4% of the population screened. In this cohort of individuals flexible sigmoidoscopy appears to have been an acceptable form of screening. The detection rate of neoplasia, particularly colorectal adenomas, is higher than that reported from studies of fecal occult blood screening. PMID- 7772103 TI - Quantitative analysis of Le(a) and Le(b) antigens in human saliva. AB - We have measured the H type 1, Le(a) and Le(b) antigens in the saliva from 129 Japanese individuals by a time-resolved europium ion fluorometric immunoassay using artificial antigen-albumin complexes as the reference substances. We confirmed that the amount of Le(b) was larger than that of Le(a) in the saliva from secretors (Le(a-b+)) and vice versa in the saliva from nonsecretors (Le(a+b )). Unexpectedly, we discovered appreciable amounts of Le(b) with small amounts of H type 1 in the saliva from the nonsecretors. The concentration of Le(b) was about 10, 6 and 35% of the concentration of the Le(a) in the saliva from the nonsecretors of the A, B and O groups, respectively. The possible formation of Le(b) from Le(a), in addition to the formation of Le(b) from H type 1, in the salivary glands is discussed. PMID- 7772104 TI - Health reform and the health of the public. Forging community health partnerships. PMID- 7772105 TI - Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. AB - OBJECTIVES: To determine whether elevated serum cholesterol level is associated with all-cause mortality, mortality from coronary heart disease, or hospitalization for acute myocardial infarction and unstable angina in persons older than 70 years. Also, to evaluate the association between low levels of high density lipoprotein cholesterol (HDL-C) and elevated ratio of serum cholesterol to HDL-C with these outcomes. DESIGN: Prospective, community-based cohort study with yearly interviews. PARTICIPANTS: A total of 997 subjects who were interviewed in 1988 as part of the New Haven, Conn, cohort of the Established Population for the Epidemiologic Study of the Elderly (EPESE) and consented to have blood drawn. MAIN OUTCOME MEASURES: The risk factor-adjusted odds ratios of the 4-year incidence of all-cause mortality, mortality from coronary heart disease, and hospitalization for myocardial infarction or unstable angina were calculated for the following: subjects with total serum cholesterol levels greater than or equal to 6.20 mmol/L (> or = 240 mg/dL) compared with subjects with cholesterol levels less than 5.20 mmol/L (< 200 mg/dL); subjects in the lowest tertile of HDL-C level compared with those in the highest tertile; and subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C level compared with those in the lowest tertile. RESULTS: Elevated total serum cholesterol level, low HDL-C, and high total serum cholesterol to HDL-C ratio were not associated with a significantly higher rate of all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina after adjustment for cardiovascular risk factors. The risk factor adjusted odds ratio for all-cause mortality was 0.99 (95% confidence interval [CI], 0.56 to 2.69) for the group who had cholesterol levels greater than or equal to 6.20 mmol/L (> or = 240 mg/dL) compared with the group that had levels less than 5.20 mmol/L (< 200 mg/dL); 1.00 (95% CI, 0.59 to 1.70) for the group in the lowest tertile of HDL-C compared with those in the highest tertile; and 1.03 (95% CK, 0.62 to 1.71) for subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C compared with those in the lowest tertile. CONCLUSIONS: Our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina in this cohort of persons older than 70 years. PMID- 7772107 TI - De novo purine nucleotide synthesis in total peripheral blood lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) PMID- 7772106 TI - Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding. AB - OBJECTIVE: To evaluate the effectiveness and safety of endometrial laser ablation and transcervical resection of the endometrium compared with hysterectomy in the surgical treatment of women with dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING: Gynaecology department of a large teaching hospital. SUBJECTS: 204 women who would otherwise have been undergoing hysterectomy for menorrhagia were recruited between August 1990 and March 1992 and randomly allocated to hysterectomy (n = 99) or conservative (hysteroscopic) surgery (transcervical resection (n = 52) and laser ablation (n = 53)). MAIN OUTCOME MEASURES: Operative complications, postoperative recovery, relief of menstrual and other symptoms, patient satisfaction with treatment after six and 12 months. RESULTS: Women treated by hysteroscopic surgery had less early morbidity and a significantly shorter recovery period than those treated by hysterectomy (median time to full recovery 2-4 weeks v 2-3 months, P < 0.001). Twelve months later 17 women in the hysteroscopy group had had a hysterectomy, 11 for continuing symptoms; 11 women had had a repeat hysteroscopic procedure; 45 were amenorrhoeic or had only a brown discharge; and 35 had light periods. Dysmenorrhoea and premenstrual symptoms improved in most women in both groups. After 12 months 89% (79/89) in the hysterectomy group and 78% (75/96) in the hysteroscopy group were very satisfied with the effect of surgery (P < 0.05); 95% (85/89) and 90% (86/96) thought that there had been an acceptable improvement in symptoms, and 72% (64/89) and 71% (68/96) would recommend the same operation to others. CONCLUSIONS: Hysteroscopic endometrial ablation was superior to hysterectomy in terms of operative complications and postoperative recovery. Satisfaction after hysterectomy was significantly higher, but between 70% and 90% of the women were satisfied with the outcome of hysteroscopic surgery. Hysteroscopic surgery can be recommended as an alternative to hysterectomy for dysfunctional uterine bleeding. PMID- 7772108 TI - Images in clinical medicine. Mycoplasma pneumoniae. PMID- 7772109 TI - Preventing deaths from asthma. PMID- 7772110 TI - Deep-vein thrombosis. PMID- 7772111 TI - Using newly deceased patients to teach resuscitation procedures. PMID- 7772112 TI - Chest roentgenogram demonstrates cephalad movement of the carina during laparoscopic cholecystectomy. PMID- 7772113 TI - Increased resting metabolic rate in patients with congestive heart failure. AB - OBJECTIVE: To examine resting metabolic rate in patients with congestive heart failure as a cause of cardiac cachexia and associated weight loss. DESIGN: Cross sectional study. SETTING: Baltimore Veterans Affairs Medical Center. PATIENTS: 20 men with heart failure (mean age +/- SD, 69 +/- 7 years) and reduced ejection fraction (mean, 0.24 +/- 0.10) and 40 healthy men (mean age, 69 +/- 7 years). RESULTS: Patients with heart failure had smaller fat-free mass than did controls (53 +/- 8 kg compared with 56 +/- 6 kg; P < 0.09), but no difference in fat mass existed (21 +/- 8 kg compared with 19 +/- 8 kg). Measured resting metabolic rate was 18% higher in patients with heart failure than in controls (1828 +/- 275 kcal/d compared with 1543 +/- 219 kcal/d; P < 0.01); no difference in caloric intake existed (2144 +/- 479 kcal/d compared with 2174 +/- 826 kcal/d). The difference in resting metabolic rate between the two groups was even more striking when indexed per kilogram of fat-free mass. CONCLUSIONS: Higher resting metabolic rate in patients with heart failure at least partially accounts for otherwise unexplained weight loss. Present caloric guidelines, which were established in healthy elderly persons, substantially underestimate the resting caloric needs of elderly persons with heart failure. PMID- 7772115 TI - Symmetry: Matte-Blanco's theory and Borges's fiction. AB - Matte-Blanco's theory reformulates the Freudian unconscious from the perspective of mathematical set theory, pointing to symmetric logic as the distinctive mark of the unconscious. Borges's fictional creations are presented as thematising and dramatising, in the act of reading, Matte-Blanco's main concepts of symmetry, bi logic and the fundamental antinomy of human beings. This study's main thesis is that aesthetic experiences, such as the reading of Borges's literary creation, may allow for a broader experience of symmetrical being than the one conveyed through everyday language. In this context, the analysis of some of Borge's themes and main stylistic devices seems to shed light on bi-logic, from the perspective of the reader's experience and creation of meaning. Borge's characteristic use of literary allusions, as well as the suggested interchangeability of reader, writer and character, are understood as devices which increase the reader's awareness of relations of resemblance, destroying chronology and differences, uniting the text and the reference. From this perspective, a main effect of Borges's creation stems from an enhanced awareness of the interplay of symmetry and asymmetry, and the problem of the translation of symmetric into asymmetric being. Borges's stories effect in the reader an experience of infiniteness, timelessness, multidimensionality and assimilation of the proper part to the whole, as the background of the theme of (asymmetric) story-telling. PMID- 7772114 TI - Does sedation help in fibreoptic bronchoscopy? PMID- 7772116 TI - Decline of serum cobalamin levels with increasing age among geriatric outpatients. AB - The level of serum cobalamin declines with increasing age. Among 100 consecutive geriatric outpatients who were seen in office-based settings for various acute and chronic medical illnesses but not for cobalamin deficiency-related diseases, 11% had serum cobalamin levels from 148 to 295 pmol/L. The average annual serum cobalamin level decline was 18 pmol/L for patients who had higher initial serum cobalamin levels (actual range, from 224 to 292 pmol/L). The average annual serum cobalamin decline was 28 pmol/L, which was much higher, for patients who had lower initial serum cobalamin levels (actual range, from 157 to 221 pmol/L). Patients with initial serum cobalamin levels of 148 pmol/L or below received treatment immediately, and their declines could not be studied. PMID- 7772117 TI - Going private: time for change. PMID- 7772118 TI - Identifying relevant studies for systematic reviews. PMID- 7772119 TI - Nutrition and lung health. PMID- 7772120 TI - Identifying complex disease genes: progress and paradigms. PMID- 7772121 TI - Should morbidity replace mortality as an endpoint for clinical trials in intensive care? PMID- 7772122 TI - Smoking, Alzheimer's disease, and confounding with genes. PMID- 7772124 TI - Sexual abuse and recovered memories. PMID- 7772123 TI - HCV-associated liver cancer without cirrhosis. AB - Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis. PMID- 7772125 TI - Community practice. A positive exercise in damage limitation. Management of aggression in elderly confused people. AB - 1. Aggression in the elderly demented person is not uncommon, and should be clearly recognised. 2. Validation and reminiscence therapy can help reduce the risk of aggressive outbursts. 3. A better understanding of how to communicate with an aggressive person can help the carers to maintain interpersonal relationships with loved ones. 4. Carers provide the main bulk of care for elderly people and therefore require help and support to enable them to do this satisfactorily. PMID- 7772126 TI - Rising emergency admissions. PMID- 7772127 TI - [Non-ketotic hyperglycinemia]. AB - Three children with non-ketotic hyperglycinaemia (NKH) is reported. Two patients had typical neonatal form of NKH, one patients had atypical form of NKH. The clinical symptoms laboratory findings and therapeutical approach are discussed. One of the patients with typical neonatal form of NKH is died, neuropatological examination revealed corpus callosal agenesis and diffuse hypomyelinisation. The two children treated with N-methyl-D-aspartate-antagonist drugs reached a significantly better clinical condition. The authors reviewed the data of the literature, especially focused on the therapeutical possibilities. PMID- 7772128 TI - Trypanosome infections of the tsetse fly Glossina pallidipes in the Luangwa Valley, Zambia. AB - Trypanosome infections of Glossina pallidipes were investigated at a site in the Luangwa Valley, Zambia between June 1991 and September 1992. Almost 3700 flies were captured, dissected, screened for trypanosome infection, and aged using both wing fray and (for females) ovarian categories. DNA probes were used to identify midgut infections. Prevalences of mature infections were 6.2% Trypanosoma vivax type and 3.1% T. congolense-type (including low prevalances of T. brucei, T. simiae and another Nannomonas species). The prevalence of infection increased with age. For both types of infection this relationship could be described by a simple 'catalytic' model which generates estimates of per capita rates of infection. Prevalences varied significantly with time independently of any changes in the age structure of the tsetse population. This may reflect temporal variation in the per capita rates of infection. PMID- 7772129 TI - Questionnaires and copyright. PMID- 7772130 TI - Health promotion in general practice. Any beneficial effect was lost in background statistical noise. PMID- 7772131 TI - Increased intracellular and plasma levels of basic fibroblast growth factor in B cell chronic lymphocytic leukemia. PMID- 7772132 TI - Growing pressure on BMJ's obituaries. PMID- 7772133 TI - Obituaries. More pages should be given to obituaries. PMID- 7772134 TI - Obituaries. Put them on an electronic bulletin board. PMID- 7772135 TI - Treating heart disease. Benefits of thrombolysis were overstated. PMID- 7772136 TI - Life expectancy in children with cerebral palsy. PMID- 7772137 TI - Changes in autonomic nervous function over a five-year period in diabetic patients. PMID- 7772138 TI - Clarifying characteristics of pericardial tamponade. PMID- 7772140 TI - Partial splenic embolization for hypersplenism. PMID- 7772139 TI - What is a normal CA-125 level? PMID- 7772141 TI - An outbreak of penicillin-sensitive strain of Neisseria gonorrhoeae in Sydney men. PMID- 7772142 TI - Distal transfer of the greater trochanter. PMID- 7772143 TI - Genetic testing for children and adolescents. PMID- 7772144 TI - Screening for prostate cancer. PMID- 7772145 TI - Mandated choice for organ donation. PMID- 7772146 TI - Risk of ovarian cancer after treatment for infertility. PMID- 7772147 TI - Nifedipine in severe aortic regurgitation. PMID- 7772148 TI - More on breast implants and connective-tissue diseases. PMID- 7772149 TI - Microalbuminuria, cardiovascular risk factors, and secondary prevention of non insulin-dependent diabetes. PMID- 7772150 TI - Oncologic aspects of augmentation mammaplasty. PMID- 7772151 TI - Pain during injection of propofol. PMID- 7772152 TI - Optic nerve ischemia: optic nerve sheath decompression alone or with optic nerve decompression. PMID- 7772153 TI - Emergency care in general practice. British Heart Foundation recommends early defibrillation. PMID- 7772154 TI - Emergency care in general practice. Courses are available. PMID- 7772155 TI - Antibiotics carried in general practitioners' emergency bags. Penicillin is necessary for suspected meningococcal disease. PMID- 7772156 TI - Handedness among surgeons. PMID- 7772157 TI - Treatment of dysfunctional uterine bleeding. Laparoscopic hysterectomy is an alternative. PMID- 7772158 TI - Care in a midwife managed delivery unit. Pregnancy and delivery require a joint midwifery and medical approach. PMID- 7772159 TI - Rising emergency admissions. Managing emergency admissions is no longer the first priority. PMID- 7772160 TI - Continuing medical education and gift authorship. PMID- 7772161 TI - Perinatal and infant postmortem examination. Postmortem reports provide valuable information. PMID- 7772162 TI - Immunisation against chickenpox. Pregnant women should be screened. PMID- 7772163 TI - Acute dissection of the thoracic aorta. Transoesophageal echocardiography has wider uses. PMID- 7772164 TI - Utility of rapid monoclonal antibody-based coagglutination test for direct detection of Vibrio cholerae O1 and/or O139 in stool samples. PMID- 7772165 TI - Sex and gender bias in illustrations in anatomy and physical diagnosis texts. PMID- 7772166 TI - Cholesterol and coronary heart disease risk in elderly patients. PMID- 7772167 TI - Airway complications after lung transplantation: is there a left-sided predilection? PMID- 7772168 TI - Coronary risk factors in people from the Indian subcontinent. PMID- 7772170 TI - Patterns of abuse in political dissidents. PMID- 7772169 TI - Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer. PMID- 7772171 TI - Restriction of fat in the diet of infants. PMID- 7772172 TI - The meaning of overseas specialist training. PMID- 7772173 TI - Patterns of mortality from asthma. PMID- 7772174 TI - Idiopathic dilated cardiomyopathy. PMID- 7772175 TI - Cold war against the Vatican? PMID- 7772176 TI - Myalgic encephalomyelitis and chronic fatigue syndrome. PMID- 7772177 TI - Re: "Suicidal behaviors in young adolescents" and "major depressive disorder and dysthymia in young adolescents". PMID- 7772178 TI - Laryngotracheal stenosis after percutaneous tracheostomy. PMID- 7772179 TI - Propofol as the sole agent for paediatric day case dental surgery. PMID- 7772180 TI - Endoscopic transthoracic sympathectomy: successful in hyperhidrosis but can the indications be extended? PMID- 7772181 TI - Posterior column sensory impairment during ambulatory extradural analgesia in labour. PMID- 7772182 TI - A case of pancreatic ascites in which endoscopic retrograde pancreatography (ERP) was used to confirm a leaking pancreatic duct. PMID- 7772183 TI - Consequences of percutaneous endoscopic gastrostomy (PEG) tubes in nursing home patients. PMID- 7772184 TI - Cutaneous involvement with Cryptococcus neoformans in AIDS. PMID- 7772185 TI - Cot mattresses and sudden infant death syndrome. PMID- 7772186 TI - Accidental hypothermia. PMID- 7772187 TI - Insecticide-treated bed nets in control of malaria in Africa. PMID- 7772188 TI - Using newly deceased patients in teaching procedures. PMID- 7772189 TI - Deep-vein thrombosis. PMID- 7772190 TI - Efficacy of validation therapy is unproven. PMID- 7772191 TI - Origin and distribution of B mtDNA lineage in South America. PMID- 7772192 TI - Variants of liposarcoma. PMID- 7772194 TI - Kafka, V. (1993) letter to the editor: On hydraulic strengthening of bones. PMID- 7772193 TI - Patient-controlled epidural analgesia for labor. PMID- 7772195 TI - The use of hope as a coping mechanism in abused women. AB - The purpose of this study was to identify how abused women use hope and to determine whether hope is a coping mechanism in their relationship with the abusers. Four focus group sessions were conducted with a sample of 24 women using a phenomenological methodology. The data analysis indicated that abused women maintain hope in four major dimensions: hope for change in their partner's behavior, hope for survival, hope as something to cling to, and hope for control of the situation. The subjects stated that hope was used as a coping mechanism to help them keep their sanity; but in this context, the subjects often saw hope as false or unreal. Thus some abused women used hope as a mechanism to attempt to resolve cognitive dissonance between their internal beliefs and the external reality of physical violence. PMID- 7772196 TI - Modelling different strategies to prevent coronary heart disease in primary care. AB - Strategies for prevention of coronary heart disease (CHD) in primary care need to take into account the number of people who require screening, further assessment, intervention and follow-up (i.e. the patient workload generated for the general practitioner) as well as the anticipated reductions in morbidity and mortality. Risks of CHD for various risk profiles were estimated from equations produced by the Framingham study. This enabled an estimate of the number of avertable CHD events to be compared against the patient workload implications for the general practitioner when different screening and intervention strategies were used. The Framingham equations were applied to a population of 5727 men and women aged 35 64 years of age registered with general practices in the south of England. Adopting an unselective approach to screening resulted in 14.1% (n = 73) of the 517 CHD events predicted over a 10 year period being averted. A limited screening strategy, involving 25% (n = 1436) of the patients would avert 5.6% (n = 29) of the predicted CHD events, whilst more extended strategies involving between 37% (n = 2131) and 46% (n = 2660) of the practice population respectively would result in between 6.9% (n = 36) and 9.3% (n = 48) of events being averted. The marginal benefit in averting CHD events decreased as more screening criteria were included. Almost all (99%) of the people identified by the selective screening strategies would require some form of intervention, predominantly lifestyle advice. Lowering the systolic blood pressure by 15 mmHg instead of 10 mmHg was equally effective as a 5% improvement in the overall rate of smoking cessation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772197 TI - Forensic odontology: age determination from adult human teeth. AB - Dentistry has several recognized specialities. Age, race and sex determination together with dental identification and facial reconstruction on skeletal material are procedures that the forensic odontologist has to master. The use of Gustafson's method to determine age in an examination of 350 teeth of living and/or dead males and females from the Heidelberg area, Germany is discussed. PMID- 7772198 TI - Blood coagulation and fibrinolysis in eclamptic patients and their correlation with the clinical signs. AB - We studied the impact of blood coagulation and fibrinolysis on the clinical features of eclamptic patients (n = 20) in Bangladesh. The variables used were edema, proteinuria, blood pressure, number of convulsions, level of consciousness at the time of admission, thrombin antithrombin complexes (TAT), antithrombin (AT) III (%) activity and antigen, D dimer fibrin degradation product and alpha 2 plasmin inhibitor-plasmin complex (PIC) in plasma. Canonical correlation analysis was made to obtain clinical index, eclampsia index and two coagulation indices. On admission, the mean values of coagulation parameters were AT III activity: 83.2% (range 57-108), TAT complex: 47.6 ng/ml (range 11.5-60), D dimer: 1,693 ng/ml (range 417-8,276) and PIC 1.4 mg/ml (range 0.4-3.3). We found a significant correlation between the eclampsia index and clinical index (r = 0.601; p = 0.01). Gestosis index, clinical index, and eclampsia index have also a strong correlation with the coagulation index (r = 0.695, p < 0.005; r = 0.871, p < 0.0001 and r = 0.805, p < 0.0001, respectively). Coagulation and fibrinolysis were markedly activated in eclampsia. The correlation between the clinical status and coagulation status in this study suggested a close relation between the coagulation and the development and progression of the disease. PMID- 7772199 TI - Protein kinase C activation is not a key step in ADP-mediated exposure of fibrinogen receptors on human platelets. AB - A selective inhibitor of protein kinase C (PKC), Ro 31-8220, blocks pleckstrin (P47) phosphorylation in platelets activated with either ADP, ADP plus synthetic thromboxane agonist U46619 and ADP plus U46619 plus epinephrine, while inducing a weak inhibition of platelet aggregation, and no significant effect on the fibrinogen binding. In platelets activated by U46619 alone, P47 phosphorylation, platelet aggregation, fibrinogen binding and serotonin release are all inhibited by Ro 31-8220. In the presence of an ADP scavenger system, U46619 induces pleckstrin phosphorylation, serotonin release and calcium mobilization but not platelet aggregation and fibrinogen binding, unless epinephrine is added. IN CONCLUSION: (1) PKC activation is required for ADP secretion; (2) ADP or epinephrine are essential for fibrinogen receptor exposure induced by U46619; (3) fibrinogen receptor exposure induced by ADP is independent of activation of PKC. PMID- 7772200 TI - A 10-year experience of pediatric brachytherapy. AB - PURPOSE: The purpose of this project was to review the brachytherapy experience in the pediatric population at the Joint Center for Radiation Therapy (JCRT) with respect to efficacy and morbidity. METHODS AND MATERIALS: Treatment outcome was reviewed for 18 children between the ages of 6 months and 23 years who received 19 implants between 1982 and 1992 at JCRT. Fourteen children received permanent Iodine-125 seed implants placed in the operative tumor bed at the time of resection. Two children received sterotactically placed afterloaded high-activity I-125 seed brain implants, and one child received a high-activity I-125 brain implant followed by a permanent I-125 seed brain implants 3 years later. One girl received a temporary Iridium-192 volume implant for a vulvar rhabdomyosarcoma. Among the 15 permanent I-125 implants, the cases included five primary brain tumors, one metastatic brain tumor, six sarcomas, and one each of the following: suprarenal neuroblastoma, hepatoblastoma, and adenocarcinoma of the pancreas. All patients underwent surgery and most patients (15 out of 18) received external beam radiotherapy to a field that included the implant. RESULTS: The median follow-up from the time of diagnosis for patients who remain alive is 55 months (range 24 to 119 months), and the median follow-up from the time of implant is 46 months (15 to 60 months). Disease was controlled in the area of the implant in 13 of 17 evaluable cases. Two patients experienced treatment-related morbidity; one patient developed severe desquamation related to an "adriamycin recall reaction," and one patient died of postoperative complications. CONCLUSION: Despite the heterogeneous mix of cases, the use of brachytherapy in this pediatric population resulted in several cases of long-term disease control, and the overall morbidity was very low. Therefore, in properly selected pediatric cases, brachytherapy appears to be an efficacious adjunct to multimodality cancer management. PMID- 7772201 TI - AAOHN. Accident investigation. PMID- 7772202 TI - Adolescents and work: risks and benefits of teenage employment. AB - 1. Adolescent employment, both legal and illegal, has been on the increase in the U.S. during the past 2 decades. According to the U.S. Department of Labor, more than 5.9 million children between the ages of 16 and 19 were legally employed in May 1994. 2. Benefits of employment include self reliance and discipline, improved organizational skills, and financial management as well as a sense of responsibility, teamwork, and exposure to occupational choices. 3. Negative effects of employment include threats to completion of developmental tasks and education, injury, toxic exposure, and illness. PMID- 7772203 TI - Latex sensitivity: an occupational health strategic plan. AB - 1. Health care workers, due to ongoing exposure to latex products, may be at risk of developing latex sensitivity. 2. The spectrum of reactions related to medical glove use varies in severity. Awareness of latex sensitivity is heightened through worker education. 3. Guidelines and interventions for occupational health nurses are outlined so that workers who present with symptoms of occupational sensitivities related to latex products can be identified and assessed. 4. Occupational health nurses are effective resources for workers and managers on issues of latex allergy and appropriate accommodation. PMID- 7772204 TI - Design of a questionnaire: occupational and environmental risks for Parkinson's disease. AB - 1. Research linking disease with occupational and environmental exposures is often predicated on obtaining accurate exposure information from affected persons. 2. Exposure history questionnaires are used to obtain comprehensive information about work history, residential history, behavioral patterns, and lifetime exposures. 3. The process of questionnaire development includes: establishing the conceptual background of the research; assuring integrity of the research questions; specifying the content domain of the questionnaire; wording, level, and formatting decisions; establishing evidence for questionnaire validity; assessment of questionnaire reliability; and final edit and polishing. 4. The careful and systematic development of an exposure history questionnaire can be a key determinant in the success of occupational health research. PMID- 7772205 TI - The economic impact of corporate wellness programs: past and future considerations. AB - 1. A primary goal of health promotion is to motivate individuals to make positive life-style changes. 2. Health promotion is multifaceted and each company must select the most appropriate method(s) of intervention for their employees. 3. In any company, a successful health promotion program requires an advocate or champion who functions as the initiator and leader for program development. Employee involvement, from inception to ongoing development of all programs, is also necessary for success. 4. To positively impact health care costs, health promotion programs should be well planned, well timed, and appropriately marketed. Needs of all workers (i.e., blue collar, minorities) should be considered. PMID- 7772206 TI - Revised NIOSH equation for manual lifting: a method for job evaluation. PMID- 7772207 TI - Readability in research. PMID- 7772208 TI - The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: a resource for occupational health. AB - 1. Hypertension continues to be a significant medical and public health concern affecting as many as 50 million Americans. 2. Early detection, treatment, and control of hypertension is important in reducing coronary heart disease, stroke, and mortality. 3. Occupational health professionals have a great opportunity to enhance detection, treatment, and control of hypertension through worksite health programs. 4. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure's publication, "The Fifth Report of the Joint National Committee," is a valuable resource to occupational health professionals in addressing employee hypertension in the workplace. PMID- 7772209 TI - Primary prevention of hypertension: a challenge for occupational health nurses. AB - 1. About one in four adults in the United States has high blood pressure on the basis of a single evaluation. Hypertension is associated with an increased risk of developing coronary heart disease, stroke, congestive heart failure, renal insufficiency, and peripheral vascular disease. 2. Weight loss, reduced sodium intake, reduced alcohol consumption, and exercise have documented efficacy as interventions to decrease high blood pressure. A number of intervention programs in community based settings and in health care provider practice based settings have documented that behavioral change and relevant reductions in blood pressure are feasible. 3. Occupational health nurses are in unique positions to both initiate and support intervention programs. Interventions could be conducted by individual occupational health nurses as well as sponsored by corporate employers or local occupational health nursing constituencies. PMID- 7772210 TI - Dealing with hypertension: using theory to promote behavioral change. AB - 1. Controlling hypertension and related disease requires that health professionals focus more attention on primary prevention strategies as a means of decreasing hypertensive risks. 2. Behavioral theories help identify attitudes, beliefs, and knowledge influencing behaviors that increase one's risk for hypertension. 3. Using information based on the behavioral theories will help occupational health nurses develop more effective programs for primary prevention of hypertension. PMID- 7772211 TI - Physical activity: one approach to the primary prevention of hypertension. AB - 1. Despite the merits of physical activity reducing the risk of hypertension and showing other health benefits, Americans continue to be relatively sedentary. 2. Low to high intensity physical activities result in a reduction in both systolic and diastolic blood pressure in middle aged to older adults. Individuals can obtain benefits by engaging in aerobic exercise, a wide variety of leisure time activities, short bouts of exercise, and even isometric work. 3. Behavioral techniques of contracting, self monitoring, and relapse prevention training offer important methods to help clients adopt and maintain physical activity. PMID- 7772212 TI - Hypertension: resources for client information. PMID- 7772213 TI - Migraine headache in occupational health settings. PMID- 7772214 TI - Linking the professional literature to nursing practice: challenges and opportunities. AB - Occupational health nurses face the challenge of rapidly changing, increasingly complex work environments. To respond, they must have access to information and know how to manage it effectively to improve their clinical performance and achieve better client outcomes. Information technology has already had an impact on nursing. Many nurses routinely use computers to access laboratory reports, client records, and administrative programs. However few nurses make use of opportunities provided by information technology to access professional literature as a tool for applying new research to their practice. PMID- 7772215 TI - Health promotion by mail. PMID- 7772216 TI - [Culturing autologous cartilage tissue for reconstructive surgery: possibilities and limits]. AB - The engineering of cartilage tissue in vitro for transplantation requires new concepts in cell culture technology. In this study a new approach is presented for an in vitro formation of cartilage transplants. First isolated chondrocytes obtained from a cartilage biopsy have to be substantially increased using monolayer culture systems. In contrast to cell amplification, the development of cartilage depends on a three-dimensional arrangement of cells and the formation or synthesis of an appropriate extracellular matrix. Bioresorbable polymer fleeces of polyglycolic acid and polylactic acid can be used as temporary cell carrier matrices to establish three-dimensional cultures of human chondrocytes. Furthermore, a perfusion culture system to provide a constant supply of nutrient into the cultures is also advantageous. With the described culture procedure, the chondrocytes maintained a differentiated phenotype showing a synthesis of new cartilage matrix. After transplantation in nude mice the pieces of solid cartilage are not resorbed or rejected and remain intact. The experiments demonstrate a promising pathway for in vitro engineering of vital tissues suitable to be used as autologous transplants in reconstructive surgery of the head and neck. PMID- 7772217 TI - [Experimental studies of chondrosynthesis for the larynx]. AB - The aim of this study was to develop and investigate techniques for stabilising and reconstruction of defects in the larynx similar to osteosynthesis. MATERIAL AND METHODS: (1) 400 extrusion forces of sutures and various screws (Howmedica) in thyroid cartilage of fresh cadavers were measured. (2) A new screw specially designed for cartilage was developed. (3) A new technique for stabilising cartilage with a screw nut made out of bone was developed. RESULTS: The extrusion forces correlate with the calcification of the laryngeal skeleton depending on the investigated area of the thyroid cartilage and the type of suture and screws that are used, respectively. Besides the increased extrusion forces the advantages of chondrosynthesis are the possibility of axial stabilisation and of exact bridging of defects with or without implants. PMID- 7772218 TI - [Treatment of acute and chronic laryngeal and tracheal stenoses in the 19th and beginning of the 20th century by tracheotomy, coniotomy, intubation and dilatation. Pictures from the history of otorhinolaryngology illustrated by instruments from the collection of the Ingolstadt Medical History Museum]. AB - Although tracheotomy had been described in the Middle Ages and especially in the 17th century in writings (Fabricius d'Aquapendente 1620) and illustrations (Scultetus 1645), there was hardly any possibility of actually performing this operation as a life-saving intervention until the middle of the 19th century. It was only after suitable cannulae had been introduced by Trousseau in 1851 (double cannula with removeable insert) that tracheotomy became a routine procedure, and it was immediately carried out in a great many cases of diphtheria, croup, typhus, and lues, which often caused critical dispnea. Within the following 25 years, all technical modifications of cannulae were devised that are in use up to this day: the flap valve for the artificial larynx (1861), inflatable cuff (1871), and extra long flexible cannula. Beginning in 1885, O'Dwyer's method of intubation became established as an alternative to tracheotomy. Both procedures, like the underlying disease itself, frequently resulted in a permanent stenosis of the larynx or the trachea rendering decannulation impossible. Since about 1870 the treatment of these stenoses, primarily by bougienage, became an important issue in laryngology, which had just been established as a discipline in its own right. The history of this evolution and the therapeutic approaches by Schrotter in Vienna and Thost in Hamburg are described in detail, including their specially devised equipment. Apart from that, other medical aspects of historical interest around the turn of the century are mentioned, such as artificial nutrition by subcutaneous injections and tracheotomy in horses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772219 TI - [Ventilation during tracheotomy in extensive, 90% laryngeal stenosis using superimposed high frequency jet ventilation via the jet laryngoscope]. AB - In a 35-year old male patient with laryngeal carcinoma an acute respiratory insufficiency with early hypoxaemia developed due to massive laryngeal stenosis. An endotracheal intubation was not possible since the available lumen was too small. Tracheotomy using local anaesthesia was not possible since spontaneous respiration with a Venturi mask applying 100% oxygen was not sufficient and the patient was becoming restless and agitated due to the hypoxaemia. Transcutaneous jet ventilation was considered to be too risky since the needle would have to pass highly vascularised tumour tissue and the detection of such a small rest lumen would have been quite difficult. Ventilating the patient using a percutaneous catheter would have been very risky as well since, due to the massive stenosis, a sufficient expiration would not be likely and therefore was considered to carry a high risk of barotrauma. The patient was ventilated under general anaesthesia via a specially designed endoscopy tube with integrated jet nozzles applying superimposed high frequency jet ventilation above the stenosis. Since it was possible to achieve sufficient ventilation during the inspection of the larynx the jet laryngoscope was left in place and the supporting apparatus was covered with sterile drapes. The tracheotomy was performed using the superimposed high frequency jet ventilation. Throughout the procedure oxygenation and ventilation were adequate. The laryngectomy performed several days later revealed a cauliflower type protrusion into the tracheal lumen and a 5 cm long stenosis of the larynx with a lumen of 3 mm. PMID- 7772220 TI - [Endoscopic techniques for the diagnosis of laryngotracheal airway obstruction in newborn infants, infants and children]. PMID- 7772221 TI - [Intubation and tracheotomy of young children with pseudocroup. Guidelines of the state attorney of the Bamberg federal court-107 UJS 382/89 (restrictions according to section 170 ABs. 2 StPO)]. PMID- 7772222 TI - [Microvascular anastomoses in reconstructive head and neck surgery]. AB - At the ENT Department of the University of Lubeck, 57 microvascular tissue transplants with 129 anastomoses (61 arterial and 68 venous) have been performed in the last three years. Arteries have always been anastomosed end to end. The venous anastomoses have primarily been performed as end-to-side unions with the jugular vein. In nine patients, great distances between the donor and recipient vessel had to be connected with venous interponates. In two cases in which veins were lacking in the neck after radical neck dissection or radiation fibrosis, we used the cephalic vein or veins of the capsule of the thyroid gland as recipient vessels. The jejunal or osteomyocutaneous transplants were first fitted into the defect before performing the anastomosis. The jejunal peristalsis and the required freedom of movement in shaping the bone necessitated this technique. Microvascular anastomosis was first performed on the transplant of the radialis flap and the neurovascular infrahyoid muscular flap, and then they were integrated into the defect. We lost two transplants postoperatively because of venous thrombosis. In this article wie describe our anastomosis technique, the frequency distribution of recipient vessels, and the rules and characteristics of microvascular anastomosis after radiation and neck dissection. PMID- 7772224 TI - [Paralysis of the facial nerve caused by "low-grade" adenocarcinoma of the parotid gland--a contribution to the differential diagnosis of Bell's palsy]. AB - Facial paresis is the only clinical symptom of two deep-seated, moderately malignant salivary duct carcinomas. The unusual course of the pareses (recurrences, varying degrees of severity) prompts the diagnosis of Bell's palsy. The final, exact diagnosis of a epithelial-myoepithelial intercalated duct carcinoma, respectively of a polymorphic low-grade adenocarcinoma, is made as late as six, respectively three, years after onset of the paresis. PMID- 7772225 TI - [Exulcerating cystadenolymphoma of the parotid gland. A case report]. AB - A recurrent adenolymphoma of the left parotid gland occurring in a 79-year-old woman is reported having caused an extensive ulceration of the epidermis, clinically suggestive of a malignant tumour. The ulcerative tumour process cannot be explained by a particular pattern of growth or a malignant transformation of the adenolymphoma. It is assumed that residual tumour cells of the initially incompletely removed adenolymphoma spread via a long-standing postoperative fistula to the epidermis leading to the uncommon ulceration. PMID- 7772223 TI - [Therapeutic concept in hemangioma--photocoagulation with the copper vapor laser]. AB - The copper vapor laser emits light with a wavelength of 578 nm and is well suited for photocoagulation of oxyhemoglobin and for selective destruction of vascular tissue. In 46 children hemangioma of different proliferation stages was treated by yellow laser photocoagulation. In 15 cases surgical treatment of the subcutaneous component of the hemangioma was necessary in addition to the laser photocoagulation. Most of the children in early proliferation stages could be treated with a single session of photocoagulation. The risk of hypotrophic oder hypertrophic scaring using the copper vapor laser is minimum (less than 1%) because the overlying dermis remains largely unaffected. In this article we present a therapy plan for conservative treatment and laser photocoagulation using the copper vapor laser. PMID- 7772226 TI - [Grass seed kernel in the efferent duct as a rare cause of acute parotitis]. AB - A patient with a case of acute parotitis resulting from a foreign body is reported. In the case presented, Stensen's duct was found to be blocked by a grass seed. Removal of this foreign body resulted in quick resolution of the patient's symptoms. PMID- 7772227 TI - [Endoscopic and extracorporeal shock wave lithotripsy of salivary calculi]. AB - Shock wave lithotripsy of salivary gland stones has become more and more efficient in the treatment of sialolithiasis during the last years. We use two different methods in our hospital: Extracorporeal shock wave lithotripsy (ESWL) and endoscopically intracorporeal lithotripsy (EISL). The results of both therapies are compatible; 60-70% could be successfully treated. The indication is different due to the localisation of the salivary gland stone. Stones that are located in the glandula or very proximal in the duct should be fragmented by extracorporeal lithotripsy. Stones located in the duct and multiple intraductal stones should be treated by the intracorporeal method. Clinical experiments showed that some salivary stones do not fragment easily. The reason is still unknown. We examined the ability of fragmentation in relation to the physicochemical analysis of the stone. The stones were examined by infrared spectroscopy. This study revealed that pure carbonate apatite stones are more difficult to destroy than stones containing some protein. PMID- 7772228 TI - [Practical significance of measuring high formant spectra in phoniatric voice assessment]. AB - The measurement of sound energy in the spectral region between 2 and 5 kHz provides additional information to the auditive assessment of voice quality. It can be applied to healthy an sick voices, e. g. in tracing the therapeutic course. Devices for measuring voice range profiles with the possibility of evaluating the high formant region are especially useful and valuable. But, nonetheless, simultaneous auditive assessment is crucial to avoid misinterpretation. Calculation of the quotient of the sound pressure level in the region between 2 and 5 kHz by the total sound pressure level allows to determine vocal sound characteristics and changes of the sound. Pre- and postoperative sound spectra obtained from the voices of patients with diseases of the vocal folds illustrate the improvement of the harmonic structure and the decrease of noise components. The measurement of the high formant intensity has proven to be appropriate for the registration of the voice quality before and after therapy in 130 cases. Although the value of these measurements is highly validated in the phoniatric practice, extensive studies and, especially, expert discussions are still needed. The authors come to terms with opinions that question the validity of the described methods. PMID- 7772229 TI - [Context effects in speech recognition of sentences]. AB - Context plays an important role in speech recognition. The goal of the present study was to quantify context effects in speech recognition using the Basle Sentence Understanding Test. This test consists of two types of sentences according to the amount of contextual information: they contain sentences with highly predictable (HP) final words and sentences with low predictable (LP) final words. The effect of different contextual situations on speech recognition was investigated in this study using the Basle Sentence Understanding Test. The speech recognition threshold of HP sentences was found to be 6 dB lower than that of LP sentences. However, contextual effects can only be demonstrated if the context is clearly understandable. In the Basle Sentence Understanding Test, this is achieved by special masking techniques. The significance of the recognition of the contextual part of the sentence with respect to the recognition of the whole sentence is different in HP and LP sentences. PMID- 7772230 TI - [Security the continuous intracutaneous suture]. PMID- 7772231 TI - [Cosmetically reliable removal of small benign skin tumors]. PMID- 7772232 TI - [A new surgical system for endoscopic paranasal sinus surgery]. AB - Functional endoscopic sinus surgery (FESS) is the treatment of choice in the majority of chronic inflammatory diseases of the paranasal sinuses. Currently used surgical instruments for FESS are based on a "grab and tear"-approach, thus predisposing to increased bleeding--especially in nasal polyps--which can significantly reduce the visual field and might lead to consecutive complications, including the injury of the anterior skull base and optic nerve. In the present paper the author introduces a new surgical system, invented by Setliff and Parsons (8), which enables the rhinosurgeon to operate in a near bloodless field, thus providing an unimpaired vision for a safer approach to the paranasal sinuses. In addition, the system ensures meticulous cutting of tissue instead of tearing, which also reduces the risk of complications. Our experiences with the "micro debrider system" have confirmed the usefulness of this instrumentarium, especially in the operative management of nasal polyps, in terms of less traumatic surgery and better visual field, thus implying fewer complications during FESS. PMID- 7772234 TI - Developmental and glucocorticoid regulation of pituitary 11 beta-hydroxysteroid dehydrogenase 1 gene expression in the ovine fetus and lamb. AB - To examine the role of 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) in the control of glucocorticoid actions in the ovine pituitary during development, we have sought developmental changes in the distribution and the level of 11 beta HSD1 mRNA by in situ hybridization. In the pars distalis, 11 beta-HSD1 mRNA was present by day 60; its amount did not change significantly until term (days 145 147) when it increased dramatically. The level of 11 beta-HSD1 mRNA increased further during the postnatal period. In contrast, 11 beta-HSD1 mRNA in the pars intermedia was not detectable until day 135; it increased in amount at days 140 143, but did not change significantly thereafter through to adulthood. We have also measured levels of both dehydrogenase and reductase activities of 11 beta HSD1 in the pars distalis of fetal sheep at day 140 and term, and of postnatal sheep at 1-2 months of age, to determine whether changes in 11 beta-HSD1 mRNA are reflected in the levels of enzyme activities. There were progressive increases in both dehydrogenase and reductase activities from day 140 to 1-2 months postnatally, although dehydrogenase activity was consistently higher than reductase activity. Finally, we have determined the effect of short-term intrafetal cortisol infusion (5 micrograms/min for 12 h) on levels of pituitary 11 beta-HSD1 mRNA by in situ hybridization. There was no effect of cortisol infusion on 11 beta-HSD1 mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772233 TI - Mechanism of action of gamma-aminobutyric acid on frog melanotrophs. AB - We have previously demonstrated that gamma-aminobutyric acid (GABA) is a potent regulator of secretory and electrical activity in melanotrophs of the frog pituitary. The aim of the present study was to investigate the intracellular events which mediate the response of melanotrophs to GABA. We first observed that GABA (1-100 microM) inhibited both basal and forskolin-stimulated cyclic AMP (cAMP) formation. The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 microM) and totally abolished by a 4-h pretreatment with pertussis toxin (0.1 microgram/ml). In contrast, the specific GABAA agonist 3-aminopropane sulphonic acid (3APS) did not affect cAMP production. Both GABA and 3APS (100 microM each) induced a biphasic effect on alpha-MSH release from perifused frog neurointermediate lobes, i.e. a transient stimulation followed by an inhibition of alpha-MSH secretion. Administration of forskolin (10 microM) prolonged the stimulatory phase and attenuated the inhibitory phase evoked by GABA and 3APS, indicating that cAMP modulates the response of melanotrophs to GABAA agonists. Ejection of 3APS (1 microM) in the vicinity of cultured melanotrophs caused a massive increase in intracellular calcium concentration ([Ca2+]i). The stimulatory effect of 3APS on [Ca2+]i was abolished when the cells were incubated in a chloride-free medium. The formation of inositol trisphosphate was not affected by 3APS, suggesting that the increase in [Ca2+]i cannot be ascribed to mobilization of intracellular calcium stores. omega-Conotoxin did not alter the secretory response of frog neurointermediate lobes to 3APS, while nifedipine blocked the stimulation of alpha-MSH secretion induced by 3APS. In conclusion, the present data indicate that, in frog pituitary melanotrophs, (i) the stimulatory phase evoked by GABAA agonists can be accounted for by an influx of calcium through L-type calcium channels, (ii) the inhibitory effect evoked by GABAB agonists can be ascribed to inhibition of adenylate cyclase activity and (iii) cAMP attenuates the inhibitory phase evoked by GABAA agonists. Taken together, these data suggest that activation of GABAB receptors may modulate GABAA receptor function. PMID- 7772235 TI - Sequence analysis of the turkey LH beta subunit and its regulation by gonadotrophin-releasing hormone and prolactin in cultured pituitary cells. AB - cDNAs encoding the precursor molecule of the turkey LH beta subunit (tLH beta) were cloned from a turkey pituitary cDNA library. The nucleotide sequence of the longest of two different tLH beta cDNA clones contained 592 bp, and included 23 bp of the 5' untranslated region (UTR) and 92 bp of the 3' UTR in addition to a 477 bp open reading frame that encoded a 39 amino acid leader polypeptide and a 120 amino acid mature apoprotein. Turkey and chicken LH beta sequences shared approximately 92 and 93% nucleotide and amino acid sequence similarities respectively. Northern blot analysis of total cellular anterior pituitary RNA showed that an approximate 800 base transcript hybridized to a 32P-labelled tLH beta cDNA probe. The gonadotrophin-releasing hormone (GnRH)- and prolactin (PRL) regulated expression of LH and PRL in dispersed pituitary cells was determined by Northern blot analysis of tLH beta and PRL steady-state mRNA levels and by RIA analysis of secreted LH and PRL. GnRH-treated cells showed increased levels of both tLH beta mRNA and secreted LH, whereas mRNA and secreted levels of PRL did not change significantly. Cells treated with PRL showed lower levels of tLH beta and PRL mRNA as well as decreased release of LH and PRL. When cells were treated with both PRL and GnRH, increases in tLH beta mRNA and secreted levels of LH observed with GnRH alone were negated, whereas the decreases in mRNA and secreted levels of PRL observed with PRL alone were abrogated. These findings suggest that PRL can down-regulate tLH beta gene expression and spontaneous release of LH as well as autoregulate PRL gene expression and spontaneous release of PRL, while GnRH appears capable of modulating the effects of PRL-regulated LH and PRL gene expression and spontaneous release. PMID- 7772236 TI - Effect of oestradiol-17 beta on the expression of oestrogen receptor mRNA in human tonsillar cells. AB - We have investigated the expression of oestrogen receptor (ER) mRNA in Ficoll separated tonsillar cells and the changes that occur with the addition of oestradiol (OE2) both in the presence and the absence of the T cell mitogen phytohaemagglutinin (PHA). The amounts of ER mRNA and beta-actin mRNA in the samples were determined by slot blotting and hybridization and quantified by densitometry. The levels of ER mRNA were normalized against the beta-actin mRNA content. In the presence of OE2 (7 x 10(-8) M) after a 10-h culture there was a significant decrease (P < 0.05) to about 66% of the control (0-h culture) ER mRNA levels. Stimulating the cultures with PHA (1 microgram/ml), without the presence of OE2, had no effect on the expression of ER mRNA. However, when OE2 was present in a 10-h culture of PHA-stimulated cells, the ER mRNA level was significantly decreased (P < 0.05) to about 60% of control levels. In 24-h cultures, the presence of OE2 and/or PHA had no effect. When separated T cell preparations from the tonsils were used, no significant effects of OE2 were seen in either the 10-h or 24-h cultures. In conclusion, OE2 downregulates the ER mRNA content in a tonsillar mononuclear cell system in vitro as it does in many primary oestrogen target cells. PMID- 7772237 TI - Thyroid hormone receptor beta mRNA expression in Sertoli cells isolated from prepubertal testis. AB - A polymerase chain reaction (PCR)-based assay was used to evaluate the expression of thyroid hormone receptor beta mRNA in Sertoli cells isolated from both prepubertal rat and piglet testes. The expression of an mRNA coding for the functional thyroid hormone receptor beta isoform, as established by the PCR assay, agrees with the presence of specific tri-iodothyronine (T3) -binding sites in the Sertoli cell nuclei of both species, as previously evaluated by displacement analysis. The results ratify the existence of a functional T3 receptor in the prepubertal testis and confirm the Sertoli cell as a specific target for thyroid hormone action on the developing testis. PMID- 7772238 TI - Growth hormone releasing peptide (GHRP-6) stimulates phosphatidylinositol (PI) turnover in human pituitary somatotroph cells. AB - Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. The precise intracellular mechanism by which this is achieved has not been deciphered although it is known to involve protein kinase C (PKC) and Ca2+ but to be cAMP-independent. We have used cell cultures of human pituitary somatotrophinomas to demonstrate powerful effects of GHRP-6 on membrane phosphatidylinositol (PI) turnover, a second messenger system which leads to activation of PKC and mobilisation of intracellular Ca2+ reserves. Incubation of somatotrophinoma cells with GHRP-6 led to a dose-dependent stimulation of rate of PI turnover. GH secretion was increased in parallel. Effects were discernable after only 15 minutes incubation and rose to a maximum at 2 hours. PI turnover was stimulated by GHRP-6 in 8 of 8 tumours examined, effects ranging from 2.1 - 7.9 fold increases. Stimulation of GH secretion by GHRP-6 was independent of presence of gsp oncogenes, emphasising the cAMP-independent nature of its effects. These results provide evidence that the GH-stimulatory effects of GHRP-6 are achieved through activation of the PI second messenger system and thus support earlier findings that PKC and Ca2+ play central roles in mediating the effects of GHRP-6. PMID- 7772239 TI - Sexual dimorphism and growth hormone induction of murine pheromone-binding proteins. AB - A number of structurally very similar pheromone-binding proteins (major urinary proteins; MUPs) are synthesized in mouse liver and rapidly excreted in the urine. Male and female inbred mice display different characteristic patterns of MUP expression. Here we present a detailed study of the RNA and protein products corresponding to specific MUP genes previously isolated from genomic DNA of the Balb/c strain. By in vitro transcription of equivalent cDNA clones, translation of the resulting RNA in the reticulocyte lysate system and isoelectric focusing, the protein products of genes BL1, BS1 and BS6 were shown to be MUP 2a, MUP 2b and MUP 4 respectively. MUPs 2a and 2b were shown to be abundant both in Balb/c male urine and among the translation products of total Balb/c male liver mRNA. Two oligodeoxynucleotide probes, oBL1A and oBS1, selective for BL1 and BS1 mRNA respectively, were chemically synthesized. mRNA that hybridized with these probes (oBL1A mRNA and oBS1 mRNA) was present at different characteristic levels in the Balb/c and C57BL/6 inbred strains. In both strains the level of expression was much higher in males than females and the male/female expression ratio of oBS1 RNA was higher than that of oBL1A RNA. Comparison of these mRNA levels with the amounts of different MUP proteins present in urine and the translation products of liver mRNA indicated that proteins other than MUP 2a and MUP 2b are coded for by the C57BL/6 oBL1A and oBS1 mRNAs. C57BL/6 mice homozygous for the lit mutation are GH deficient and transcribe MUP genes at a level much lower than that obtaining in normal mice of either sex, indicating that transcription is induced by GH in both males and females. When lit/lit mice were treated with GH under two different regimes, MUP gene transcription was partially induced to different degrees and the level of oBL1A mRNA was induced more highly than that of oBS1 mRNA. Thus there exists a correlation between the inducibility of these mRNAs and their level of expression in females relative to males; oBL1A mRNA is both more highly expressed in females and more readily induced by GH than oBS1 mRNA. This suggests that the male and female expression patterns are due to differential inducibility of different MUP genes together with a stronger inducing stimulus in males. GH administered continuously by infusion repressed MUP gene expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772240 TI - High-level expression of recombinant porcine LH receptor in baculovirus-infected insect cells or caterpillars. AB - Porcine LH receptor ectodomain was overexpressed in insect cells and lepidopteran larvae using the recombinant baculovirus expression system. A low multiplicity of infection yielded the largest active production, of approximately 10(7) receptors/cell or 3 micrograms active receptor/mg total protein in infected cells. The truncated ectodomain solubilized with Triton X-100 bound its ligand with a high affinity which was comparable with that of the native membrane receptor. Increasing the multiplicity of infection resulted in an optimum protein production of 0.6 mg receptor/mg total protein in infected cells. This receptor was largely inactive, probably trapped within aggregation pools. Active receptor could be recovered by dilution of the samples. No secretion of recombinant receptor was ever observed whatever the conditions of infection. Expression of the recombinant receptor in insect larvae was also tested. This low-cost system failed both to increase the amount of active receptor and to induce secretion into the haemolymph. Two methods remain for producing sizeable amounts of active receptor with this baculovirus/insect cell system. One relies on immunoaffinity purification of the active protein and requires large-scale production, and the other is based on the purification of overexpressed inactive receptor followed by renaturation. PMID- 7772241 TI - Sequence analysis of vasotocin cDNAs of the lamprey, Lampetra japonica, and the hagfish, Eptatretus burgeri: evolution of cyclostome vasotocin precursors. AB - We determined the nucleotide sequences of cDNAs encoding precursors of vasotocin (VT) from two cyclostomes, the lamprey Lampetra japonica and the hagfish Eptatretus burgeri, for estimation of their phylogenetic relationships. Although only 47% similarity was found between the VT cDNAs, the predicted VT precursors of the lamprey and the hagfish were both composed of a single peptide, VT, Gly Lys-Arg and a neurophysin, as has been shown for precursors of vasopressin (VP) family hormones, including VP, VT and molluscan conopressin. The central region of the lamprey neurophysin was very similar to those of previously characterized gnathostome neurophysins. Conspicuously, all the positions of 14 Cys residues were conserved in the lamprey neurophysin. The C-terminal region did not have a distinctive Leu-rich core segment, which is always found in the glycopeptide (copeptin) moiety of VP precursors. In contrast, the hagfish neurophysin showed at least two insertions and one deletion in the conserved central region including 14 Cys residues, but contained a potential N-linked glycosylation site and had a high proportion of Leu residues in the C-terminal region, like the neurophysin of another hagfish, Eptatretus stouti. The evolutionary relationships of the precursors of VP family hormones among the lamprey, hagfish, gnathostomes and a mollusc were estimated by a maximum likelihood method. The phylogenetic tree with the highest bootstrap probability showed that the lamprey VT precursor is more closely related to the gnathostome VT and VP precursors than to the hagfish VT precursors. PMID- 7772242 TI - Production and characterization of recombinant chicken insulin-like growth factor II from Escherichia coli. AB - Recombinant chicken (c)IGF-II has been produced in Escherichia coli after first modifying a plasmid that coded for a human (h)IGF-II fusion protein. The cIGF-II fusion protein, deposited in bacterial inclusion bodies, was dissolved under reducing conditions, desalted, subjected to anion-exchange chromatography and refolded. Recombinant cIGF-II was then released from the fusion protein using a genetically engineered serine protease and purified to homogeneity by reverse phase HPLC. In vitro analysis of recombinant cIGF-II revealed differences between cIGF-II and its human counterpart. Recombinant cIGF-II was less potent than hIGF II in stimulating protein synthesis in rat myoblasts. This appeared to be due to a decreased affinity for the type-1 IGF receptor. The human and chicken peptides were similar, however, in studies assessing binding to the type-2 IGF receptor and to IGF-binding proteins. Moreover, recombinant cIGF-II and hIGF-II were equipotent in both biological and receptor binding studies in chick embryo fibroblasts, suggesting that there may be a difference between mammalian and avian type-1 IGF receptors. PMID- 7772243 TI - Interaction of LHRH with growth hormone-releasing factor-dependent and independent postnatal development of somatotrophs in rat pituitary cell aggregates. AB - Addition of LHRH for 40 h to aggregate cell cultures of 14-day-old rat pituitary significantly decreased the number of [3H]thymidine ([3H]T)-incorporating cells which immunostained for GH protein as well as the number of [3H]T-labelled cells expressing GH mRNA detectable by in situ hybridization with a digoxigenin labelled riboprobe. The effect at the level of GH protein was seen at a dose of 1 nM LHRH. However, the effect at the GH mRNA level required a higher dose of LHRH (10 nM) or a longer incubation time (64 h). Treatment of the cultures for 40 h with 0.1 nM GH-releasing factor (GRF) provoked a 54% increase in the number of [3H]T-labelled cells containing GH mRNA and a 30% increase in the number of cells immunostained for GH protein. The latter effects of GRF were completely blocked by simultaneous addition of LHRH (1 nM) to the cultures. In the absence of GRF, LHRH (1 nM) also had an inhibitory effect on the total number of cells containing GH mRNA and a comparable effect on the total number of cells stained for GH protein. The present data show that LHRH is capable of inhibiting the GRF independent as well as the GRF-dependent development of somatotrophs in postnatal rat pituitary in culture. PMID- 7772244 TI - [Cell adhesion molecules and the immune system]. AB - Cellular interactions are controlled by complex mechanisms which come into play at the receptors on the cell surface (adhesion molecules: selectins, integrins, superfamily of immunoglobulins), the soluble cell mediators (cytokines) and the components of the tissue matrix (fibronectin, collagen, etc.). Disturbance of one of these systems may induce a pathological condition. The physiological state of the individual therefore depends on the balance of all these components. In the development of inflammation, adhesion molecules play an essential role in the localisation of the inflammatory response. At this level, the vascular endothelium, a governing barrier for the exchanges between blood and the tissues, plays an active part in regulation of the transcapillary permeability, control of proliferation of haematopoietic cells and the phases of the inflammatory response. After they have marginated, the active cells migrate by diapedesis towards the site of inflammation by creation of chemotactic signals as the adhesion between the cells is insufficient to induce their migration. The adherence phenomena depend on a process that is strictly controlled by the cytokines and enable intervention of cell-cell reactions and cell-protein recognition of the extra-cellular matrix. Cytokines play a key role in control of the expression and/or avidity of membrane receptors for ligand(s). An appropriate and rapid response of the circulating cells depends on coordination of the train of events that regulate the functional expression of the adhesion molecules. Use of specific antibodies that prevent cell adherence opens very important therapeutic possibilities because a single blockage of cell adhesion can have an immediate direct impact on development of the inflammatory response. PMID- 7772245 TI - [From IgE to the cell adhesion molecule]. AB - The aim of this work is to contribute to increasing our knowledge of asthma. The IgE can't alone be imputed in the anaphylactic reaction. Asthma is a bronchial inflammatory disease. The secretion of lymphokines increases the inflammatory response. The eosinophils cells damage the respiratory epithelium. The mast cells and the basophils cells release the chemical mediators and also the cytokines. The adhesion molecules situated in the cell membrane permit leukocyte cells to integrate with extracellular matrix during intra-tissue migration. Adhesion molecules may play a primary role in the pathogenesis of inflammatory response. The key role of the CD4 + T lymphocytes subset appeared in the last years. PMID- 7772246 TI - [Methods for studying cytokines in biological media]. AB - Accurate and sensitive methods for the measurement of cytokines in biological fluids are an absolute prerequisite for a proper use of these mediators in clinical practice. The authors describe the numerous molecular forms under which cytokines can possibly circulate. The potential influence of inhibitors (autoantibodies, soluble receptors) on cytokine assays is discussed. Blood collection for cytokines needs a particular attention to prevent a possible contamination by endotoxins which can trigger cytokines cellular production after sampling. If bioassays historically preceded immunoassays, these last techniques are now very popular, but there is an urgent need for standardisation between the different kits commercially available. In addition, in situ detection of cytokines using molecular biology is an helpful complementary technique to the measurement of circulating cytokines. PMID- 7772247 TI - [Therapeutic strategy in asthma: special cases and pseudo-asthma]. AB - Therapeutic strategy of asthma such as that described by international consensus must sometimes be modified in certain situations, the triggering agent or subsequent complications. Account should also be taken of pseudo-asthmas, i.e. other illnesses accompanying the sibilant dyspnoea. The therapeutic principles of each of these conditions are set out and specially emphasize asthma in pregnancy and states of resistance to corticosteroids. PMID- 7772248 TI - Budesonide: treatment of bronchial asthma during childhood. AB - Nowadays inhaled corticosteroids are the first step in treating inflammation of the airways. It is evident that these drugs are not free of side effects; however, the fact that at present the most commonly used method is by inhalation and that these drugs undergo metabolic changes in the lung, makes them safe in that a part of the side effects, which are observed when they are administered systemically, disappear. Budesonide was one of the last corticosteroids for topical application to appear on the market and its powerful anti-inflammatory action together with in versatility (it can come in aerosol form using MDI or in solution for nebulizers as well as in dry powder) make it possible to use during all stages of a child's development. In 75 children treated with Budesonide over a long period (18-24 months) we were able to evaluate the drug's clinical efficacy in the reduction in number and intensity of attacks registered together with their accompanying symptoms. Significantly (p < 0.001) it were able to restrict the bronchodilatory medication needed to control their asthma. Similarly, we were able to verify that the FEV1 was normalized and that the Peack Flow was stabilized. We were not able to find any interruption in the hypothalamo hypophysio-suprarenal axis and the weight-height curves continued to evolve chronologically. With regards to the side effects, three cases of colonization candidiasis were recorded through there were no clinical repercussions and treatment did not need to be suspended. PMID- 7772249 TI - Evolutionary conservation of function among mammalian, avian, and viral homologs of the Bcl-2 oncoprotein. AB - The bcl-2 gene was originally cloned because of its involvement in B-cell lymphomas and encodes a 25-kD integral membrane protein that has been shown to inhibit programmed cell death (also termed apoptosis) in a wide variety of circumstances. The Epstein-Barr Virus (EBV) also has been implicated in B-cell malignancies and interestingly contains an open reading frame (BHRF-1) predicting a 19-kD protein with 22% homology to Bcl-2. To compare the functions of p26-Bcl-2 and p19-BHRF-1, we stably introduced expression plasmids encoding these proteins into a murine interleukin-3 (IL-3)-dependent hemopoietic cell line, 32D. Removal of IL-3 from cultures of control-transfected 32D cells resulted in internucleosomal DNA cleavage (a hallmark of programmed cell death) and loss of cell survival. In contrast, 32D cells containing high levels of p26-Bcl-2 or p19 BHRF-2 proteins exhibited prolonged survival and markedly delayed DNA degradation under the same conditions of IL-3 deprivation. As a first attempt to determine the functional importance of amino acid sequences that are conserved between the Bcl-2 and BHRF-1 proteins, we used site-specific mutagenesis to replace two conserved cysteine residues with alanines (positions 158 and 219) in the human Bcl-2 protein. Comparisons of the wild-type and cysteine-minus human Bcl-2 proteins in S49 lymphoma cells revealed equivalent ability to block glucocorticoid-induced cell death and DNA fragmentation, indicating that these two conserved cysteines are not critical for Bcl-2 oncoprotein function. Investigations in 32D cells of an avian homolog of Bcl-2 cloned from the chicken also revealed conservation of function with the human Bcl-2 protein, despite the presence of a 48-amino-acid region of divergent sequence. Taken together, these data demonstrate that despite marked differences in their predicted amino-acid sequences, the human, chicken, and EBV versions of Bcl-2 have retained the structural characteristics necessary to interface with pathways involved in the regulation of programmed cell death in murine cells. The findings thus contribute to the mapping of functional domains in Bcl-2 proteins, and raise the possibility that the EBV-encoded p19-BHRF-1 protein may be able to substitute for p26-Bcl-2 in the development of some types of cancer. PMID- 7772250 TI - Retinoblastoma control element binding proteins are induced during in vivo terminal differentiation of the liver and bind to the DBP promoter. AB - Growth regulation of terminal differentiation was studied by analysis of the promoter of the transcription factor D-site binding protein (DBP) using nuclear extracts from rat liver undergoing regeneration or from normal liver early in development. Four proximal binding sites for nuclear proteins were identified, three of which showed significant quantitative or qualitative changes in associated factors upon growth induction. Two of these sites bound factors common to the retinoblastoma control element and these proteins were induced upon terminal differentiation of the liver. These factors were also rapidly down regulated upon induction of regenerative growth and consequent dedifferentiation. These results provide a link between the regulation of growth and differentiation in an in vivo model system. PMID- 7772251 TI - SV40 T antigen directed by a powerful erythroid enhancer-promoter produced sarcomas and pancreatic tumors but not erythroid-specific tumors in transgenic mice. AB - We have expressed the simian virus 40 (SV40) large T antigen oncogene in erythroid tissues of mice to test its ability to immortilize erythroid cells. A transgene construct was built in which the SV40 large T antigen structural gene was linked to erythroid-specific enhancer and promoter sequences. The enhancer employed was the human beta-globin family microlocus control region, and the promoter sequences were derived from the human beta-globin promoter. Transgenic mice were generated and they expressed T antigen in the bone marrow and spleen cells. Yet, no hematopoietic neoplasia arose in these mice. Instead, after a lag period of 2-6 months, the mice developed soft tissue sarcomas and pancreatic islet-cell tumors that expressed high levels of T antigen. PMID- 7772252 TI - Cloning and characterization of human tissue inhibitor of metalloproteinases-3. AB - The tissue inhibitors of metalloproteinases (TIMPs) comprise a family of proteins, of which two members have so far been described in humans. We have cloned and sequenced a third human TIMP (hTIMP-3) from phorbol ester differentiated THP-1 cells stimulated with bacterial lipopolysaccharide. The open reading frame encodes a 211-amino-acid precursor including a 23-residue secretion signal. The mature polypeptide has a calculated molecular weight of 21.6 kD and includes an N-linked glycosylation site near the carboxyl terminus. The protein is quite basic, having a predicted isoelectric point of 9.04. We have mapped the single gene encoding human TIMP-3 to chromosome 22. By Northern analysis, transcripts for TIMP-3 were identified in a broad cross-section of tissues examined from both embryonic and adult origin. In all tissues except the placenta, the predominant transcript was 5.0 kb in size, with minor bands around 2.4 and 2.6 kb comprising no more than about 10% of the signal. In the placenta, the smaller bands accounted for close to 50% of the signal. Human TIMP-3 shows slightly closer amino acid sequence similarity to TIMP-2 (44.3%) than to TIMP-1 (38.4%), but is most closely related to a recently reported chicken TIMP, chIMP-3 (80.8% amino acid; 77.7% nucleic acid similarity. PMID- 7772253 TI - An analysis of Xenopus tyrosine kinase genes and their expression in early development. AB - Xenopus laevis and X. borealis were screened for tyrosine kinase genes using the polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR and 34 X. laevis and 23 X. borealis tyrosine genes were identified. Eighteen of the genes represented novel tyrosine kinase family members. The rest could be classified into known tyrosine kinase subfamilies, of which however only three have been previously identified in Xenopus. Eight clones, including bFGFR (xFGFR1) and potential Trk, Ins R., Fak, Fyn, and Abl homologs, were used to probe temporal and spatial gene expression in early development. Quantitative RT-PCR and whole mount and in situ hybridization showed that most of these mRNAs were present throughout development and were broadly distributed, mainly in ectodermal and mesodermal derived tissues. At the blastula stage, bFGFR mRNA was detected within the ectoderm and a gradient of expression was noted within the invaginating mesoderm. The unexpected promiscuous expression of many tyrosine kinase genes in early development is discussed. PMID- 7772254 TI - Isolation of a cDNA encoding a metal response element binding protein using a novel expression cloning procedure: the one hybrid system. AB - A new method for isolation of cDNA clones encoding sequence-specific DNA-binding proteins is described. This method, the one-hybrid system, is based on the use of reporter genes whose transcription can be activated through synthetic cis elements recognized by the sought-after DNA-binding protein. These reporter genes are used for in vivo screening of a library of cDNAs fused to a DNA fragment encoding the GAL4 activation domain. cDNA clones expressing the appropriate fusion proteins lead to activation of these reporter genes in transformed yeast cells. We have used this approach to isolate a mammalian cDNA clone encoding a sequence-specific DNA-binding protein that recognizes the metal response elements (MREs) of the metallothionein (MT) genes. The protein encoded by this cDNA, M96, shows similarity to the trithorax proteins. Expression of a functional DNA binding form of M96 requires Zn2+ ions. The recombinant protein binds to several different MREs but fails to recognize nonfunctional mutant MREs. M96 may be involved in the activation of MT genes in response to heavy-metal ions. PMID- 7772255 TI - Cloning and characterization of the promoter region of the murine alpha-4 integrin subunit. AB - To study the differential expression of the murine VLA-4 (alpha 4 beta 1) integrin, the 5'-flanking region of the gene for the alpha subunit (alpha 4m) was isolated and a cDNA for alpha 4m was obtained with reverse transcriptase polymerase chain reaction (RT-PCR). The cDNA sequence contained a difference in the signal peptide region compared to the previously described cDNA (Neuhaus et al., 1991). As a consequence, another start codon is predicted, resulting in a decrease in size of the signal peptide. This was confirmed by genomic sequencing. The promoter region was delimited by ribonuclease protection assay (RPA) and transfection experiments fusing 5'-upstream fragments to the luciferase gene. A fragment extending from -936 to +221 was capable of controlling the expected cell type-specific expression. Sequence comparison of the mouse alpha 4m promoter region with the human alpha 4h promoter revealed little homology. Like most integrin subunits, alpha 4m lacks TATA anc CCAAT boxes. Putative recognition sites for DNA-binding nuclear factors (AP1, AP2, Sp1, and PU1) were identified. The characterization of the promoter region and further identification of the transcription regulatory elements should provide insight in the regulation of alpha 4m integrin gene expression. PMID- 7772256 TI - Functional analysis of the cell-specific enhancer in the human proopiomelanocortin gene by beta-galactosidase histochemical staining. AB - Nucleotide sequences responsible for the cell-specific expression of the human proopiomelanocortin (POMC) gene were analyzed by histochemical staining of beta galactosidase in culture cells transfected with chimeric genes containing the 5' flanking regions of the human POMC gene fused to the Escherichia coli lacZ gene. The chimeric genes were stably introduced into various culture cells, including AtT-20 cells, which express the endogenous mouse POMC gene. Whereas the control gene containing the cytomegalovirus enhancer was expressed in all cell lines tested, only AtT-20 cells supported the efficient transcription of the gene containing 2.9 kb of the human POMC 5'-flanking region. These results indicate that the stable transfection-expression system utilizing the histochemical detection of the gene expression is a useful method for the analysis of cell specific gene expression. These results have also confirmed that the trans-acting factors in mouse AtT-20 cells interact with the human POMC gene promoter region and activate the transcription of the gene. Deletion analysis has demonstrated that the profiles of the transcriptional activity of the various human POMC-lacZ fusion genes are similar to those of the rat POMC gene described previously. Comparison of the human and the rat 5'-flanking sequences revealed close homology in several regions, which might be involved in the efficient transcription of the POMC gene in AtT-20 cells. PMID- 7772257 TI - cDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a murine cytochrome P450 gene, Cyp1b1. AB - C3H mouse embryo fibroblast cells, designated 10T1/2, can be transformed by physical and chemical agents including polycyclic aromatic hydrocarbons. In a previous report (Shen et al., Proc. Natl. Acad. Sci. USA 90, 11483-11487, 1993), we identified a cytochrome P450 gene induced by polycyclic aromatic hydrocarbons (PAHs) that is different from 1A1 or 1A2, and which we tentatively named P450CMEF. Here, we report the entire cDNA sequence of P450CMEF (5,128 bp) and the amino acid sequence deduced from it (543 residues). A comparison of the latter sequence with known cytochrome P450s indicates that P450CMEF is in a new subfamily of family 1 of the P450 superfamily. Accordingly, the Committee on Standardized Cytochrome P450 Nomenclature designated the gene Cyp1b1. Exposure to various aryl hydrocarbons (2.5 hr) induced Cyp1b1 mRNA in 10T1/2 cells to different degrees: 2,3,7,8-tetrachlorodibenzo-p-dioxin, 7,12 dimethylbenz[a]anthracene, benz[a]anthracene, benzo[a]pyrene, and beta naphthoflavone were strong inducers; alpha-naphthoflavone and 3 methylcholanthrene, were moderate inducers; and benzo[e]pyrene was a weak inducer. PMID- 7772258 TI - Differential protein binding and transcriptional activities of HNF-4 elements in three closely related CYP2C genes. AB - A functional binding site for a liver-enriched transcription factor, hepatocyte nuclear factor-4 (HNF-4), has previously been identified around -100 in the CYP2C2 promoter and proposed to be a common regulatory motif for the hepatic expression of many CYP2 genes. The transcriptional activity of the proximal promoters of three closely related cytochrome P450 genes (CYP2C1, CYP2C2, and CYP2C3) have been compared in HepG2 cells and correlated with the relative binding affinities of the HNF-4 motifs in the genes for proteins in liver, kidney, and HepG2 extracts that react with antisera to HNF-4. Gel-shift assays suggested that these highly similar motifs bound HNF-4 with significantly different affinities. The relative binding affinities to the protein in liver extracts were estimated by competitive gel-shift binding, and the binding affinity of CYP2C2 was two-fold and eight-fold greater than that of CYP2C1 and CYP2C3, respectively. These affinity differences correlated well with the transcriptional activities of either the minimal hepatic promoters (117 to 135 bp of 5'-flanking region) of the genes in HepG2 cells or minimal CYP2C2 promoters containing the HNF-4 motif from each gene. Identification of the CYP2C3 site was somewhat indirect; the HNF-4 element in the CYP2C3 promoter could be converted to a motif with binding affinity and hepatic cell-specific transcriptional activity similar to that of CYP2C2 by a single nucleotide substitution. The activities of the minimal promoters did not correlate well with hepatic expression of each gene in vivo, as estimated previously by the concentration of mRNA in livers of untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772259 TI - Is alcohol consumption a cofactor in the development of acquired immunodeficiency syndrome? AB - Excessive alcohol (EtOH) consumption and acquired immunodeficiency syndrome (AIDS) are two major public health problems in the United States. Overwhelming evidence is showing that heavy EtOH ingestion broadly suppresses the various arms of immune response, seriously impairing the body's normal host defense to invading microbes and tumorigenesis. The onset of clinical symptoms of AIDS (low CD4+ T cells count, opportunistic infections, and tumors) is quite variable among HIV+ individuals with a mean incubation time 3-10 years following seroconversion. Because of the deleterious effects of chronic EtOH consumption on cytokine release, immune response, host defense, nutritional status, and oxidative stress, it has been believed to be a possible cofactor that could enhance the host's susceptibility to infections, and subsequently increase the rate of AIDS development. The purpose of this review is to present evidence indicating clinical disorders during EtOH ingestion in murine AIDS. These EtOH-induced abnormalities may promote a more rapid development of AIDS in HIV-infected individuals. PMID- 7772260 TI - Effect of alcohol on gastrointestinal cell regeneration as a possible mechanism in alcohol-associated carcinogenesis. AB - Chronic ethanol consumption is a major risk factor for oropharyngeal, esophageal, and rectal cancer. Because hyperregenerative gastrointestinal mucosa has an increased susceptibility towards chemical carcinogens and thus influences carcinogenesis, various studies have been performed to evaluate the effect of chronic ethanol consumption on mucosal cell turnover. In the rat, morphometric analysis showed that in chronically ethanol-fed rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue, and the base of the tongue were significantly enlarged. The size of the basal cell layer was increased and the stratification of the cells was altered. The percentage of cells in S-phase of the cell cycle was significantly higher in ethanol-fed rats compared to controls. In addition, mucosal atrophy was found. Similar to the oropharynx, in the esophagus chronic ethanol consumption increased cell proliferation depending on salivary gland function, because only in the presence of the salivary glands was this stimulative effect of alcohol on cell turnover found. Subsequently, chronic ethanol ingestion significantly stimulated crypt cell production rate in the rectum, in an age-dependent manner. This hyperregeneration, which was only observed in the rectum but not in the remaining colon, was associated with an expansion of the proliferative compartment of the crypt. Such an expansion is correlated with increased risk for rectal cancer. In addition, crypt cell production rates in the rectal crypts can be correlated with mucosal acetaldehyde concentrations, underlining a toxic effect of acetaldehyde on the rectal mucosa that is answered by compansatory hyperregeneration. These data from the rat model could be confirmed in humans. In conclusion, chronic ethanol consumption leads to mucosal hyperregeneration in gastrointestinal mucosa associated with a high risk for cancer and may therefore be at least one mechanism by which alcohol exerts its cocarcinogenic effect. PMID- 7772261 TI - Hepatocellular carcinoma in alcoholics. PMID- 7772262 TI - Alcohol drinking in rats injected ICV with 6-OHDA: effect of 8-OHDPAT and tropisetron (ICS 205930). AB - 6-Hydroxydopamine (6-OHDA) was administered ICV to Wistar male rats. Lesioned animals displayed lower preference for ethanol (ETOH) than sham-operated rats. Among 6-OHDA lesioned rats only 9% became high-preferring whereas 20% of sham operated animals became high-preferring ones. Both tropisetron (the antagonist of 5-HT3 receptors) and 8-OHDPAT (the 5-HT1A receptor agonist) reduced ETOH drinking in high-preferring rats. However, in 6-OHDA lesioned rats the effect of tropisetron was reduced although 8-OHDA retained its effect on ETOH consumption. These results suggest that brain DA neurons are involved in tropisetron action but are not responsible for antipreference effect of 8-OHDPAT. PMID- 7772263 TI - Altered brain sensitivity to ethanol in mice after MPTP treatment. AB - Previous studies demonstrated the role of the dopaminergic receptors in brain sensitivity to ethanol. The present study was designed to assess the relative contribution of the nigrostriatal component to this brain sensitivity. Adult male C57BL mice were given 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) injections (30 mg/kg daily for 2 consecutive days). The treatment decreased the striatal dopamine level by 35% from the control level, and the number (Bmax) of dopaminergic receptors was increased by 67%. Ethanol-induced sleep time was reduced in the MPTP-treated mice, as compared to controls, and this gap progressively widened during the 3 weeks of testing to 29%. Brain ethanol levels upon awakening increased by 22%. The results suggest that the nigrostriatal dopaminergic pathways play a major role in determining brain sensitivity to ethanol which may represent an important component in the addictive process. PMID- 7772264 TI - Role of brain [Mg2+]i in alcohol-induced hemorrhagic stroke in a rat model: a 31P NMR in vivo study. AB - One hundred percent of anesthetized rats administered 6.6 gm/kg of ethanol IP died within 10-35 min of alcohol injection; upon autopsy of the brain all demonstrated profound subarachnoid and intracranial bleeding, clear signs of hemorrhagic stroke. Pretreatment of rats with 4 mumol/min MgCl2, but not saline, via IV administration (for 30-45 min), prevented hemorrhagic stroke in all animals so treated with 6.6 gm/kg ethanol. Administration of the stroke dose of alcohol resulted in rapid (within 3-5 min) and marked deficits in whole brain intracellular free Mg ([Mg2++]i) as observed by in vivo 31P-NMR spectroscopy. Intracellular pH (pHi) and the phosphocreatine [PCr]/[ATP] ratio also fell following a significant fall in brain [Mg2+]i). Brains of rats that exhibited strokelike events, upon death and autopsy, demonstrated continued and marked intracellular acidosis with progressive fall in the [PCr]/[ATP] ratio and elevation of inorganic phosphate (Pi) and [H+]i; these events were not accompanied by any rises in systemic arterial blood pressure. Rats pretreated with MgCl2 exhibited relatively stable brain [Mg2+]i, and essentially unchanged pHi, [PCr], [ATP], or [Pi] following alcohol administration, although such animals exhibited threefold alterations in plasma Mg2+, as measured by ion selective electrodes. These observations suggest that high alcohol ingestion can result in severe vasospasm, ischemia, and rupture of blood vessels probably as a consequence of depletion of brain [Mg2+]i, events that can be prevented by Mg2+ pretreatment. PMID- 7772265 TI - Effects of chronic alcohol administration on lactational performance in the rat. AB - Lactating rats, with litters adjusted to eight pups on day 2, were implanted with an atrial catheter on day 3 of lactation. Alcohol in doses of 0.0, 1.0, or 2.0 g/kg BW was infused from day 5 to 12. The blood alcohol levels (BALs) achieved following infusion of the initial doses were maintained for 4 hours daily by infusion. To control for the reduced food intake in alcohol administered groups, rats receiving alcohol doses of 0.0 and 1.0 g/kg BW were pairfed to 2.0 g/kg BW alcohol group. For infusion, combinations of 50% dextrose, 30% alcohol in saline and saline solutions were used for 0.0 and 1.0 g/kg BW alcohol groups whereas the 2.0 g/kg BW alcohol group received 30% alcohol in saline thereby equilizing the calorie intake of the three experimental groups. On day 12, pups were separated from the dams at 0800 h, a catheter extension was attached at 0900 h and baseline blood samples for prolactin level were taken at 1000 h. Following infusion of initial alcohol doses, samples were taken for BALs. Additional samples for BALs were removed 2 h after continuing the infusion. At the end of 4-h infusion, blood samples were taken for alcohol and postinfusion prolactin levels. In groups designed to study the suckling-induced prolactin release, pups were weighed and returned to the dams. Subsequent blood samples were taken 30 min after initiation of suckling. In nonsuckled groups, blood samples were obtained at corresponding time periods. BALs were determined by head space gas chromatography and plasma prolactin by a double antibody radioimmunoassay. Suckling latency and milk consumption during the 30 min of suckling were measured. Dams' and litter weights were determined on days 2, 5, and 12 of lactation. Infusion of alcohol for 8 days from day 5 to 12 of lactation did not affect maternal body weight. However, litters nursed by dams receiving 2.0 g/kg BW alcohol weighted less on day 12 compared to all other groups. Suckling latencies did not differ among groups. Milk consumed during the 30 min of suckling was lower for the alcohol administered groups. The inhibitory effect on milk consumption was greater for the 2.0 g/kg BW group than in the 1.0 g/kg BW alcohol group. Alcohol infusion did not affect the basal prolactin, whereas, the higher dose (2.0 g/kg BW) inhibited suckling-induced prolactin release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772266 TI - Creatine kinase release from isolated EDL muscles in chronic ethanol-treated rats. AB - Chronic ethanol abuse has been shown to cause damage to skeletal muscle in animals and patients as reflected by elevated serum levels of cytosolic enzymes and histological examination. The present study investigated the hypothesis that elevated serum creatine kinase levels in ethanol-treated animals vs. sucrose control animals may result from increased enzyme release or efflux from muscle. Creatine kinase release was measured from extensor digitorum longus (EDL) muscles isolated from rats chronically treated for 28 weeks with ethanol and from sucrose fed controls. The in vitro cumulative release of creatine kinase over a 2-h period was significantly higher in the ethanol-treated animals. Consistent with an increased release of enzyme into the bath, creatine kinase levels in muscle homogenates at the end of the incubation period were lower in the ethanol-treated animals. Creatine kinase levels in serum obtained from trunk blood samples were statistically higher in the ethanol-treated animals compared to sucrose controls. These findings demonstrate increased enzyme release from fast-twitch skeletal muscle in chronic ethanol-treated rats. PMID- 7772267 TI - The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated glutamate release in the hippocampus of the fetal and adult guinea pig. AB - The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated L-glutamate (Glu) release was determined in transverse hippocampal slices of the near-term fetal guinea pig and the adult guinea pig. Exposure of the slices to 48 mM ethanol inhibited K(+)-stimulated Glu efflux. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective adenosine A1 receptor antagonist, blocked the ethanol-induced inhibition of K(+)-stimulated Glu efflux in the near-term fetal and adult hippocampus. In the near-term fetus, 2-chloro-N6 cyclopentyladenosine (CCPA), a selective adenosine A1 agonist, and exogenous adenosine each blocked K(+)-stimulated Glu efflux similar to that produced by 48 mM ethanol. In the adult, although K+ increased Glu efflux in the presence of CCPA or adenosine, the magnitude of increase was less than that of the K(+) stimulated Glu efflux for the control conditions. Exposure to ethanol alone or ethanol plus CPT produced a transient increase in endogenous adenosine efflux in the near-term fetal and adult hippocampus, which was not temporally related to the ethanol-induced inhibition of K(+)-stimulated Glu efflux. Overall, the data indicate that adenosine A1 receptor activation mediates ethanol-induced inhibition of stimulated Glu release in the hippocampus of the near-term fetal and adult guinea pig. PMID- 7772268 TI - Detection of aldehyde dehydrogenase deficiency in Chachi Indians, Ecuador. AB - The activity of mitochondrial aldehyde dehydrogenase (ALDH2) was tested by isoelectric focusing of hair root extracts from 50 Chachi Indians (Ecuador). Quality of extracts and the intactness of cytoplasmic and mitochondrial enzymes were ascertained by assaying of phosphoglucomutase (PGM) and malate dehydrogenase (MDH) in the same extracts. Three of the 39 successfully assayed Chachi Indian samples showed virtual absence of the ALDH2 band on the isoelectropherogram, and the control enzymes were stained normally in these subjects. These data confirm the existence of a mitochondrial ALDH deficiency among South American Indians. The molecular origin of the ALDH2 deficiency in this population is unknown. PMID- 7772269 TI - Apparent monomorphism of ALDH2 in seven American Indian populations. AB - Deficiency of mitochondrial aldehyde dehydrogenase (ALDH2) has been previously reported in South American Indians. We therefore assayed five individuals from each of five South American Indian populations (Quechua, Karitiana, Ticuna, Surui, Guahiba), and two North American populations (Maya and Moskoke) for the presence of the Oriental ALDH2(2) variant. These samples were also surveyed for other alleles altering ALDH2 function. Allele-specific amplification assay (ASA) did not detect the ALDH2(2) allele in any of the New World populations studied. The entire coding sequence of the ALDH2 cDNA was enzymatically amplified in partially overlapping fragments. Each fragment was digested using restriction endonucleases and subfragments 148-285 b.p. in length were analyzed by the single stranded conformation polymorphism (SSCP) technique. No variants were detected within the coding region of the ALDH2 gene in any of the seven American Indian populations. Three potentially correct explanations for these results are suggested. First, an ALDH2 polymorphism is present but undetectable by SSCP; second, none of the studied individuals were ALDH2 negative; third, the polymorphism occurs beyond the coding region of ALDH2 gene. PMID- 7772270 TI - Acetaldehyde-modified lysozyme function: its potential implication in the promotion of infection in alcoholics. AB - Incubation of lysozyme with acetaldehyde (0.44 M) at room temperature for 2 h produces a 62% inhibition of enzymic activity. Because the active site cleft contains tryptophyls, asparagine, glutamine, and an arginine residue, and because acetaldehyde reacts with indoles, amides, and guanidines, it is suggested that these sites are likely ones for alkylation. The epsilon-amino groups of lysines on the surface of the molecule are also susceptible to covalent modification. Total acetylation of lysozyme has been reported to inactivate the enzyme. These results suggest the possibility that inactivation of a fraction of the lysozyme activity by acetaldehyde may decrease the effectiveness of the enzyme in chronic alcoholics, thereby leading to an increased potential for susceptibility to bacterial infection. PMID- 7772271 TI - Alcohol consumption and risk of cancer in humans: an overview. AB - Recent epidemiologic data continue to support alcoholic beverage consumption as a cause of cancer of the mouth, pharynx, larynx, esophagus, and liver. The effect of a given alcohol intake on absolute risk of these cancers depends on the prevalence of other risk factors. Whether alcoholic beverage consumption is a cause of cancer of the breast or large bowel is unclear. Alcohol intake appears not to increase risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium, or of melanoma. Indirect epidemiologic evidence suggests that alcohol may be a weak causal factor for pancreatic cancer. Additional research is needed to determine whether middle-aged women who drink moderately may experience a slight increase in longevity if they decrease alcohol intake. A number of biologically plausible mechanisms exist by which alcohol may cause cancer. PMID- 7772272 TI - Alcohol-related cancer risk: a toxicokinetic hypothesis. AB - Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further. PMID- 7772273 TI - Significance of T-cell stimulation by altered peptide ligands in T cell biology. AB - Investigations of T-cell responses to altered peptide ligands have provided functional evidence that a T-cell receptor can interpret subtle structural changes in its ligand, highlighting the complexity of this antigen receptor signaling system. Over the past year, observations from many studies have suggested several roles for such analog peptides in various aspects of immune responses. Collectively, these data strongly suggest the existence of naturally occurring altered peptide ligands in the endogenous peptide repertoire, that can actively participate in the development and shaping of T-cell immunity. PMID- 7772274 TI - Natural killer cell receptors. AB - In the past year, significant strides have been made in understanding natural killing, the process whereby natural killer cells lyse target cells. Recognition of susceptible targets and activation now appear to be mediated by a natural killer cell receptor that binds carbohydrate determinants on target cells and initiates target lysis. Conversely, receptors have been identified that bind MHC class I molecules on targets that inhibit natural killer cell activation. These findings provide the basis for understanding the molecular processes in the initial steps of natural killing. PMID- 7772275 TI - B cell activation, tolerance and antigen-presenting function. AB - Recent advances in the understanding of the collaboration between T cells and B cells have provided a novel framework within which to analyse the mechanisms of B cell tolerance and its breakdown. Of particular interest has been the finding that B cell anergy is due to defective antigen receptor mediated functions, while the antigen-processing machinery and CD40-dependent activation pathways are unaffected. Thus, the anergic B cell, which otherwise has a short lifespan, can be rescued by a number of regimes to participate in autoimmune responses. PMID- 7772276 TI - Innate immunity. PMID- 7772277 TI - Signaling mechanisms through cytokine receptors that share signal transducing receptor components. AB - Most of the receptors for soluble factors functioning in immune and hematopoietic systems belong to the cytokine receptor family. These receptors often share common signal transducing receptor components with other members of the same family. Such receptors and signal transducers possess no intrinsic tyrosine kinase domain but have recently been found to be associated with members of a JAK family of cytoplasmic tyrosine kinases. The JAK kinases become activated after ligand-induced dimerization of the receptor components. This activation appears to link the cell surface receptors to the nuclear genes through tyrosine phosphorylation and activation of latent cytoplasmic transcription factors called signal transducers and activators of transcription (STATs). PMID- 7772278 TI - Molecular immunobiology of macrophages: recent progress. AB - Macrophage molecules involved in adhesion, signalling, secretion and interactions with pathogens and T-helper lymphocytes have been cloned and defined using monoclonal antibodies and genetic disruption. Studies of the regulation of macrophage differentiation and activation by cytokines have yielded insights into the heterogeneity of their functions in natural and acquired immunity, including immunity to infections by mycobacteria and HIV. PMID- 7772279 TI - The role of natural killer cells in host-parasite interactions. AB - Natural killer cells contribute to resistance to infectious organisms, and may also influence the nature of the adaptive immune response associated with infection. During the past year, their role in these events has been more clearly defined. In addition, the results of several recent studies that have begun to define the mechanisms by which natural killer cells recognize their targets will be important in further elucidating their role in infectious disease. PMID- 7772280 TI - Innate immunity of insects. AB - Insects are particularly resistant to microorganisms. Their host-defense system relies on several innate reactions: upon injury, the immediate onset of two proteolytic cascades leading to localized blood clotting and to melanization, the latter process involving production of cytotoxic molecules (namely reactive oxygen intermediates); the phagocytosis of bacteria and the encapsulation of larger parasites by blood cells; the induced synthesis by the fat body of a battery of potent antimicrobial peptides/polypeptides which are secreted into the hemolymph where they act synergistically to kill the invading microorganisms. The insect host defence system shares many of the basic characteristics of the mammalian acute phase response, especially at the level of the coordinate control of gene expression, where similar cis-regulatory and inducible transactivators appear to play key functions. The powerful techniques developed to study the genetics of Drosophila provide a unique opportunity to dissect the development and differentiation of this primordial immune system and may contribute to our understanding of the innate immune response in higher organisms. PMID- 7772281 TI - Complement-immunoglobulin interactions. AB - Normal circulating immunoglobulin may control complement binding to targets and thereby the manifestations of autoimmune disease. Molecular analysis of IgG and IgM mutants suggests that C1q binding by IgG utilizes a core Glu-X-Lys-X-Lys motif (where X is any amino acid). Additional amino acids, particularly homologous proline residues at position 331 in IgG and 436 in IgM, appear critical for classical pathway initiation. Glycosylation of IgG heavy chain is important in C1q binding, as well as glycosylation of IgA heavy chain for alternative pathway initiation. Additional recent evidence suggests an important role for C3 in antigen presentation. The data also raise the possibility that C3 plays a significant role in the intracellular antigen processing pathway. PMID- 7772282 TI - Structure, function and cellular expression of complement anaphylatoxin receptors. AB - The past year has seen significant advances in determining the important structural-functional domains of the complement C5a anaphylatoxin receptor. The current model suggests a two-site binding motif in which part of the amino terminal extracellular domain of the receptor is recognized first by the amino terminal end and disulfide-linked core of the C5a ligand. This is followed by interaction of the carboxy-terminal end of C5a with a second, and as yet undefined, site on the receptor that results in activating appropriate signal transduction pathways via receptor coupled G proteins. Another recent advance has been the discovery that the C5a receptor is expressed on non-myeloid cells, suggesting that C5a confers previously unexpected functions on certain target tissue cells, including bronchial and alveolar epithelial cells, hepatocytes, astrocytes, and vascular endothelial cells. PMID- 7772283 TI - Structure and function of the pentraxins. AB - Over the past two years, the three-dimensional structure of the serum amyloid P component was defined by X-ray diffraction, the first such visualization of a pentraxin. Binding sites for calcium, ligands and complement were identified. New fusion proteins with amino acid sequence homology to the pentraxins were described, and new insights were gained into pentraxin phylogeny, biosynthesis, ligands, complement activation, leukocyte reactivity and biological functions in vivo. PMID- 7772284 TI - Supply and transport of peptides presented by class I MHC molecules. AB - Three observations suggest that the proteasome, transporter associated with antigen processing (TAP) and class I MHC molecules are co-adapted for the generation, transport and loading of specific peptides. Firstly, TAP preferentially transports peptides close in length to the optimum for class I loading; secondly, genetic variation in TAP specificity focusing in the carboxy terminal of the peptide correlates with preferences among class I molecules for different peptide carboxy-termini; thirdly, TAP associates directly with empty class I molecules and is released by successful peptide loading. This conclusion puts in question the significance for class I loading of proteolytic processing and peptide generation in the endoplasmic reticulum. PMID- 7772285 TI - Molecular chaperones in antigen presentation. AB - As is the case with most proteins of the secretory pathway, the biogenesis of MHC class I and class II molecules occurs in association with molecular chaperones. Considerable progress has been made in identifying the chaperones involved and recent studies on two of these, calnexin and invariant chain, have shown that they influence multiple processes including protein stability, folding, assembly and intercellular retention. PMID- 7772286 TI - Chemistry of peptides associated with MHC class I and class II molecules. AB - Recent developments have led to a clearer understanding of the association between peptides and MHC molecules. It is now clear that the peptides presented by MHC class I or class II molecules follow stringent rules that are different for each allelic product. The allele-specific interaction usually involves a sequence of nine amino acids spanning the MHC groove. For class I molecules, the entire peptide ligand is involved in allele-specific interaction with MHC but for class II, the peptides are longer and the nine amino acid sequence is roughly central to the peptide. Allele-specific interactions are brought about by anchoring peptide side chains in complementary pockets in the MHC groove. The sum of allele-specific peptide-MHC interaction requirements can be described as a motif, characterized by number, spacing and specificities of anchors, as well as the more degenerate preferences at non-anchor positions within the nonamer stretches. Such information is useful for T-cell epitope predictions. PMID- 7772287 TI - Novel molecules related to MHC antigens. AB - Several types of molecules related to classical class I and II antigens of the MHC have been recently discovered. At the same time we have learnt more about the functions of non-classical (class Ib) antigens. This has shed light on the possible evolutionary origins and the likely roles that these molecules may play in the immune response. PMID- 7772288 TI - [XV Congreso Nacional de Microbiologia (Madrid, 25-28 September 1995). 50 years of microbiology in Spain]. PMID- 7772289 TI - Forty years of screening programmes for antibiotics. AB - The article gathers the reflections on the experiences of forty years doing research on the screening of natural product in the pharmaceutical industry. Over those years new technologies have improved the methodology. However, the steps followed in such a research are the same: the isolation and cultivation of microorganisms; the definition of assays with well defined targets; the demonstration of their efficacy for the discovery and selection of active substances produced by microorganisms; the classification and structural determination of the new products; and the study of their therapeutical efficiency. Examples of the processes which led to the production of several antibiotics (fosfomycin, cefoxitin and thienamycin) are described. One important lesson that the author has learnt is that microorganisms have unique fingerprints and that generalization should be avoided in the planning of this work. PMID- 7772290 TI - [History of microscopy in Spain]. AB - Nowadays, many Spanish research centers have excellent electronic microscopy services. The current situation, however, should not allow us to forget that the initial steps of microscopy in Spain were very difficult. The construction of excellent optical microscopies in the late XIX century, and their almost immediate introduction in Spain, coincides with a period of thriving scientific activity in our country. Both micrography and histology saw the highlights of their development in Spain, with scientists such as Ramon y Cajal, Rio Hortega, Ferran, Simarro, among others, all of them widely known at present. This article evokes briefly the vicissitudes of Spanish microscopy, from its very beginning in 1843, when the Allgemeine Anatomie by Jacob Henle was translated into Spanish, to present. Scientific historical facts in this article are often accompanied with anecdotes, which show the human aspect of those great scientists. The persevering task carried out by researchers whose names have been recorded in the history of Spanish science and technology, have established the grounds in which our current development is based. PMID- 7772291 TI - New methods in Salmonella genetics. AB - This review summarizes several recent developments in Salmonella genetics; some of the procedures described can be easily adapted to Escherichia coli and have also potential applications in non-enteric bacteria. The novel methods outlined include genetic mapping procedures, ancillary tools for cloning, a strategy for analyzing DNA-protein interactions in vivo, a method for plasmid curing and a procedure for the detection of bacterial virulence genes. PMID- 7772292 TI - Genetic regulation of nitrogen fixation in Rhizobium meliloti. AB - The soil bacterium Rhizobium meliloti fixes dinitrogen when associated with root nodules formed on its plant host, Medicago sativa (alfalfa). The expression of most of the known genes required for nitrogen fixation (nif and fix genes), including the structural genes for nitrogenase, is induced in response to a decrease in oxygen concentration. Induction of nif and fix gene expression by low oxygen is physiologically relevant because a low-oxygen environment is maintained in root nodules to prevent inactivation of the highly oxygen-sensitive nitrogenase enzyme. The genes responsible for sensing and transducing the low oxygen signal, fixL and fixJ, encode proteins (FixL and FixJ, respectively) that are homologous to a large family of bacterial proteins involved in signal transduction, the two component regulatory system proteins. The two components consist of a sensor protein, to which FixL is homologous, and a response regulator protein, to which FixJ is homologous. The sensor protein respond to an activating signal by autophosphorylating and then transferring the phosphate to its cognate response regulator protein. The phosphorylated response regulator, which is often a transcriptional activator, is then able to activate its target. A cascade model of nif and fix gene regulation in R. meliloti has been proposed, whereby FixL acts as an oxygen sensor as the initial event in the cascade and transmits this information to FixJ. FixJ, which possesses a putative helix-turn helix DNA-binding motif, then activates transcription of the nifA and fixK genes. The nifA and fixK gene products, are transcriptional activators of at least 14 other nif and fix genes. PMID- 7772293 TI - Genes involved in the regulation of invertase production in Saccharomyces cerevisiae. AB - The expression of Saccharomyces cerevisiae SUC genes is exclusively regulated by catabolic repression, mediated by glucose. Genes involved in this process have been defined by means of mutants either unable to express invertase or with constitutive phenotype, although none of the genes is specific for invertase regulation. The affected genes in mutants unable to produce invertase are designated SNFX. These genes can be assorted into two groups considering either their function in regulation of gene expression or their epistatic relationships. Mutants with constitutive phenotype have been selected either by resistance to 2 deoxyglucose or by suppression of snf mutations. Among the different genes previously outlined, some of which code for transcription factors, only the MIG1 product, a "zinc finger" protein, shows a clear capacity of binding DNA in vitro. Besides the ON/OFF switch mechanism of the expression of SUC genes, some genes seem to play a role in modulating invertase expression, either hindering or stimulating transcription. A model to define the relationship between the different gene products involved in the regulation of transcription of the SUC genes is proposed. PMID- 7772294 TI - Sibling species of the Saccharomyces sensu stricto complex in Spain. AB - By genetic hybridization, molecular karyotyping and Southern hybridization with the ADC1 promoter probe three species Saccharomyces cerevisiae, S. paradoxus and S. bayanus were identified among wild Saccharomyces sensu stricto yeast in Spain. Wine strains fermenting melibiose belong to the biological species S. bayanus (syn. S. uvarum). S. kluyveri has been detected karyotypically. PMID- 7772295 TI - Diversity of actinomycetes and fungi on seaweeds from the Iberian coasts. AB - As a part of a screening program for natural products from microorganisms, 465 actinomycetes strains and 278 fungal strains were isolated from 44 seaweed specimens (Rhodophyta and Phaeophyta), collected in the Iberian peninsula seashore (Atlantic and Mediterranean coasts). Six different isolation procedures were followed, and seven isolation media were used, some of which included seawater in their composition. The isolated microorganisms were identified to the level of species or genus by microscopic morphology. Determination of species of Streptomyces was performed through total fatty acid analysis by gas chromatography. Richness and diversity of the Streptomyces and actinoplanetes species isolated from the seaweeds are compared, taking into account the geographic location of the samples. Most of the fungi recovered from these samples were terrestrial, although several marine species (Dendryphiella arenaria, Dendryphiella salina, Varicosporina ramulosa, Corollospora intermedia and Asteromyces cruciatus) were also isolated. PMID- 7772296 TI - [In vitro tests of the antagonistic behavior of Trichoderma spp. against pathogenic species of the horticultural region of La Plata, Argentina]. AB - The antagonistic properties of seven Trichoderma species in front of the pathogens Fusarium oxysporum, F. equiseti, F. solani, Sclerotinia sclerotiorum, S. minor, Rhizoctonia sp. and Sclerotium rolfsii was evaluated in vitro. Those microorganisms were isolated from horticultural soils of La Plata in order to test the antagonistic-pathogenic relationship. Dual cultures on PDA 2% were used. All the species of Trichoderma grew in the culture medium with a colonization value higher than 50%. Differences in the antagonistic behaviour of the pathogens were observed depending on the species with which they interacted. The presence of diffusible metabolites to the medium was demonstrated in almost 80% of the pathogens antagonists tested. PMID- 7772297 TI - [Maclyn McCarty: a forgotten genius. 50 years after the rediscovery of DNA]. PMID- 7772298 TI - [Andre Lwoff (1902-1994)]. PMID- 7772299 TI - [10 suggestions for the Spanish scientist]. PMID- 7772301 TI - Inhibition of signal-regulated protein kinases by plant-derived hydrolysable tannins. AB - A variety of hydrolysable tannins purified from Phyllanthus amarus are potent inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit (cAK) with IC50 values (concentrations for 50% inhibition) in the range 0.2-1.7 microM. The three most effective compounds of this series of hydrolysable tannins have five phenolic substituents. These three compounds are also the most effective inhibitors of wheat embryo Ca(2+)-dependent protein kinase (CDPK), rat brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and Ca(2+) calmodulin-dependent myosin light chain kinase (MLCK). The order of sensitivity for protein kinase inhibition by the hydrolysable tannins studied is cAK > CDPK > PKC > MLCK. Thus the IC50 values for protein kinase inhibition by the most potent compound are 0.2 microM (for cAK), 1.8 microM (for CDPK), 26 microM (for PKC) and 56 microM (for MLCK) when protein kinase affinity is measured using synthetic peptide substrates. These hydrolysable tannin inhibitors found are the most specific and potent plant-derived inhibitors of cAK yet found. PMID- 7772300 TI - Synthesis of enantio-manoyl oxides: modifiers of the activity of adenylatecyclase enzyme. AB - Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate with m chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en 18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-oxo-8 alpha,13-epoxilabd-14-en 18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound. PMID- 7772302 TI - A novel protein from mung bean hypocotyl cell walls with acetyl esterase activity. AB - An acetyl esterase was purified from cell walls isolated from mung bean hypocotyls. The purified enzyme had an apparent Mr of 43,300 and an apparent pI > 9. It rapidly deesterified triacetin and p-nitrophenylacetate and slowly released acetate from beet and flax pectins, the deesterification rate being increased by previous demethylation of the pectins. No significant peptide sequence identity between the acetyl esterase and any known protein could be found in protein data bases. PMID- 7772304 TI - Biotransformation of an acyclic neolignan in rats. AB - The biotransformation of an acyclic neolignan, (+)-erythro-(4,7-dihydroxy-3 methoxy-1'-allyl-3',5'-dimethoxy)-8-O-4' neolignan, in rats has been investigated. After administration of (+)-erythro-(4,7-dihydroxy-3-methoxy-1' allyl-3',5'-dimethoxy)-8-O-4'-++ +neolignan to rat by intraperitoneal injection, urine and faeces were collected. A small amount of (+)-erythro-(4,7-dihydroxy-3 methoxy-1'-allyl-3',5'- dimethoxy)-8-O-4'-neolignan and its metabolic product were obtained from an ethyl acetate extract of the urine, and the largest amount of the same metabolic product was obtained from a dichloromethane extract of the faeces. The sole metabolic product was identified as (+)-(4-hydroxy-3-methoxy-1' allyl-3',5'-dimethoxy)-8-O-4'-neolignan++ + by spectroscopic methods. Furthermore, biotransformation of (+)-erythro-(4,7-dihydro-3-methoxy-1'-allyl 3',5'- dimethoxy)-8-O-4'-neolignan by intestinal bacteria in rat faeces was also investigated in vitro. Consequently, (+)-erythro-(4,7-dihydroxy-3-methoxy-1' allyl-3',5'-dimethoxy)-8-O-4'-++ +neolignan was reduced to the same metabolic product and no other metabolic products were produced. These results suggested that intestinal bacteria were concerned in the specific dehydroxylation of (+) erythro-(4,7-dihydroxy-3-methoxy-1'-allyl-3',5'-dimethoxy)-8-O-4'-++ +neolignan in rats. PMID- 7772303 TI - Isolation of dihydrofolate and folylpolyglutamate synthetase activities from Neurospora. AB - The possible association of dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) in Neurospora crassa (FGSC 853, wild type) has been examined using mycelial extracts prepared and fractionated in the presence of protease inhibitors. DHFS and FPGS were assayed by following the incorporation of labelled glutamate into dihydrofolate and methylenetetrahydrofolate polyglutamate, respectively. Both of these activities were predominately cytosolic in mycelia that were harvested 24 hr after spore inoculation of defined minimal medium. Relatively small amounts of total mycelial DHFS activity were associated with mitochondrial fractions isolated by differential centrifugation. In contrast, ca 20% of the mycelial FPGS activity was mitochondrial. Treatment of the mitochondrial fractions with Triton X-100 suggested that these activities were not latent under the assay conditions employed. Separate peaks of DHFS and FPGS activity were observed when (NH4)2SO4 fractionated protein was desalted and chromatographed on columns of either Mono Q HR, DEAE-cellulose, heparin agarose, Matrex Green A or Reactive Green 5. Gel filtration indicated average Mr values of 52 and 66 x 10(3) for DHFS and FPGS protein, respectively. Dihydrofolate synthetase protein was purified over 1000 fold by a protocol that included chromatography on DEAE-cellulose, DEAE-Sephacel, heparin agarose and Matrex Green A. The isolated protein lacked ability to glutamyl conjugate 5,10-methylene tetrahydrofolate. SDS-polyacrylamide gel electrophoresis of the Matrex Green A peak fractions revealed a major protein band of average Mr 52 x 10(3) whose concentration appeared to parallel DHFS activity. FPGS protein (average Mr 66 x 10(3)), which lacked ability to glutamyl conjugate dihydropteroate, was recovered by a similar protocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772305 TI - Cyclosporins from Tolypocladium terricola. AB - New natural cyclosporins were isolated from the mycelium of surface cultivated fungus Tolypocladium terricola. The chemical structures of [Leu4] CS and [MeLeu1] CS = cyclosporin-J, were deduced from the NMR and mass spectral data. Biological activity of new cyclosporins is reported based on the proliferative mitogen stimulation test. PMID- 7772306 TI - Diterpenes from Solidago rugosa. AB - Investigation of the roots and aerial parts of Solidago rugosa afforded the known diterpenes kolavenol, hardwickiic acid, (-)-kaur-16-en-19-oic acid, (+)-manool, (+)-3 beta-hydroxymanool, manoyl oxide and ent-abietic acid. In addition, the new labdane diterpene (+)-18-tigloyloxymanool and four new ent-abietanes were obtained. The structures of all known and new compounds were elucidated by spectroscopic methods, especially high-field 1H and 13C NMR, and inverse 1H-13C correlation techniques, as well as chemical transformations. Six diterpenes were tested against Mycobacterium tuberculosis and M. avium, but showed no significant activities with minimum inhibitory concentrations of > 100 micrograms ml-1. PMID- 7772307 TI - Bioactive anthraquinone glycosides from Picramnia antidesma spp. fessonia. AB - A bioactivity guided fractionation, using KB cells and brine shrimp assays, of the methanolic extract from the leaves of Picramnia antidesma yielded two known anthraquinones, aloe-emodin and aloe-emodin anthrone, and three new aloe-emodin C glycosides, named picramnioside A, picramnioside B and picramnioside C. Structures were established by spectroscopic methods (UV, IR, mass spectrometry, 1H and 13C and 2D NMR including COSY 45, HMQC, HMBC and ROESY). CD was used to establish the absolute configuration of the picramniosides. PMID- 7772309 TI - The restoration or preservation of sensation in the oral cavity following ablative surgery. AB - The importance of sensory feedback from the oral cavity is evaluated in the context of functional rehabilitation following ablative surgery using three techniques that restore or preserve sensation. Nerve grafts to restore the continuity of sensory nerves interrupted during ablative surgery, as well as the role of sensate flaps and the protection of palatal sensation following soft palate resection or total glossectomy, are discussed. PMID- 7772308 TI - Three acylated flavone glycosides from Sideritis syriaca. AB - From the aerial parts of Sideritis syriaca a new flavone glycoside, 5,8,3' trihydroxy-4'-methoxyflavone 7-(6"'-O-acetylsophoroside) was identified together with apigenin 7-(6"-p-coumaroylglucoside) and apigenin 7-(4"-p coumaroylglucoside) which are reported for the first time in the genus Sideritis. The compounds were characterized using 1H NMR, 13C NMR, MS and chemical methods. PMID- 7772310 TI - The anterior extension face-lift. AB - OBJECTIVE: To describe a face-lift technique with emphasis on extension of the temporal incision into the lateral orbital area. This modification serves several beneficial ends but must be used only in carefully selected patients. Gathering of excess skin in the lateral orbital area is prevented, eliminating the typical disparity between relatively tight lower and middle facial skin and flaccid upper facial skin, which is commonly seen after rhytidectomy. The anterior extension also helps to support the lower eyelid, which is helpful when lid laxity exists or when concomitant blepharoplasty is performed. SETTING: A private cosmetic surgery center. PARTICIPANTS: Thirty-five patients undergoing rhytidectomy (15 primary and 20 revision procedures). OUTCOME MEASURE: Patient satisfaction at 3 months after surgery. RESULTS: Thirty-four (97%) of 35 patients were pleased with their results. CONCLUSIONS: The anterior extension face-lift can provide excellent results in carefully selected patients. We have found this procedure to be especially helpful in patients undergoing revision surgery and in older patients with facial skin laxity. PMID- 7772311 TI - The importance of maintaining the alar-facial sulcus in nasal reconstruction. AB - The alar-facial sulcus is an important topographical region because it represents a junctional zone of three cosmetic units: the nasal base, the medial aspect of the cheek, and the upper lip. Too often, the sulcus is violated by transposition flaps that have been harvested from the cheek to reconstruct defects of the nasal alar lobule. When the sulcus is violated by surgery, it is difficult to restore a completely natural appearance. For this reason, we suggest an alternative method of reconstructing the alar lobule through the use of an interpolated flap. When defects extend into the alar-facial sulcus, reconstruction of the sulcus is necessary and should be accomplished with a separate skin flap from that used to repair the nasal component of the defect. When a single flap is used to reconstruct both lobule and sulcus, restoration of a completely natural-appearing sulcus is rarely achieved and usually involves multiple surgical procedures often facilitated by aggressive flap contouring, secondary intention healing, and Z plasty. We describe our methodology in restoring the alar-facial sulcus after nasal reconstruction. PMID- 7772312 TI - A graduated method of tip graft fixation in rhinoplasty. AB - Projection of the nasal tip has gained increased recognition as a measurable and visual characteristic that has an impact on the results of aesthetic rhinoplasty. Autologous cartilage tip grafts have been used in many techniques to increase tip projection and contour the tip during rhinoplasty. This article introduces a graduated method of tip graft fixation correlated with specific clinical measurements related to tip projection. After careful analysis of tip projection and contour, a predictable graft fixation technique can be selected to obtain the desired degree of nasal tip projection and sculpting. PMID- 7772313 TI - Role of the argon beam coagulator in facial rejuvenation surgery. AB - OBJECTIVE: To compare the hemostatic effectiveness of a new electrosurgical unit, the argon beam coagulator, with current methods of electrocoagulation. DESIGN: A nonrandomized control trial of 20 patients undergoing rhytidectomy. SETTING: Two academic tertiary referral medical centers. PARTICIPANTS: Twenty male patients having moderate to major degrees of facial ptosis. INTERVENTION: All 20 patients underwent a standard rhytidectomy with hemostasis provided by the argon beam coagulator on the right side and conventional electrocoagulation on the left side. OUTCOME MEASURES: Improved hemostasis with minimal depth of injury, length of procedure, decreased blood loss, edema, and ecchymosis, and the ability to coagulate indiscriminately around and over neural tissue without damage (all listed in the literature as advantages of the argon beam coagulator). RESULTS: Poor hemostatic ability was observed with concomitant increased incidence of blood loss, edema and ecchymosis, major hematoma, and length of surgery. Also noted were increased rates of flap compromise and the potential for damage to vital neural structures. CONCLUSION: Our results do not agree with the list of advantages attributed to the argon beam coagulator in the literature. PMID- 7772314 TI - The Rieger flap for nasal reconstruction. AB - OBJECTIVE: To repair surgical defects of the middle and distal third of the nose. DESIGN: The anatomic and technical design of the Rieger (dorsonasal) flap is described. CONCLUSION: When performed on properly selected patients, the Rieger flap is an aesthetically predictable, one-stage procedure. PMID- 7772315 TI - Maxillary swing approach for resection of tumors in and around the nasopharynx. AB - The efficacy of the anterolateral approach to the nasopharynx and its vicinity was evaluated. Using this maxillary swing approach, we have removed tumors in and around the nasopharyngeal region in 26 patients. Among them, 18 suffered from recurrent primary nasopharyngeal carcinoma after external radiotherapy, three patients had chordoma, two had schwannoma, one had adenocarcinoma of the nasopharynx, and one had malignant fibrous histiocytoma. The last patient had a recurrent deep-lobe parotid gland tumor localized in the paranasopharyngeal space. The facial wounds in all 26 patients healed primarily with no evidence of necrosis of the maxilla. Seven patients developed palatal fistula, five of them subsequently healed, whereas one patient required surgical closure and one had to wear a dental plate. This group of patients was followed up from 4 to 42 months (median, 15 months). Among the 18 patients with recurrent nasopharyngeal carcinoma, five had local recurrence, four died of other conditions, and nine of them are still alive with no evidence of disease. This gives an actuarial control of tumor in the nasopharynx of 42% at 3.5 years. In the eight patients remaining, one died of recurrent chordoma, two are alive with recurrent disease, and five are free of disease. Exposure of the nasopharynx and the paranasopharyngeal space is possible using the anterolateral approach. The associated morbidity is low. PMID- 7772316 TI - The use of calvarial bone in nasal reconstruction. AB - OBJECTIVE: To demonstrate the utility of calvarial bone as a primary graft choice in nasal reconstruction. DESIGN: Case series. SETTING: Academic tertiary care center. PATTERN: Thirty-five consecutive patients who underwent split calvarial bone grafting to the nasal dorsum between June 1988 and September 1993 and who had post-operative follow-up. OUTCOME MEASURES: Serial clinical examination to assess volume loss, movement of the graft, and complications. Standardized photographs to assess nasal contour. RESULTS: Fixation of the graft was accomplished using a technique that promotes bone-to-bone healing without fixation screws or wires. The most common complication was seroma or hematoma of the scalp (8%). There were no dural tears or intracranial complications. Long term donor site morbidity consisted of one case of local alopecia (2.8%). A good nasal contour was achieved in 97% of patients. CONCLUSION: Based on the experimental evidence reviewed and our clinical experience, split calvarial bone is recommended as a material of choice for nasal dorsal reconstruction. PMID- 7772317 TI - Late proptosis following orbital floor fracture repair. AB - OBJECTIVE: Late proptosis is an unusual complication of orbital floor fracture repair. We report 12 cases and propose a classification scheme and differential diagnosis for this rare complication. DESIGN: Retrospective multi-institutional case review. SETTING: Two tertiary referral centers. RESULTS: We report 12 cases of late proptosis following orbital floor fracture repair. Causes of late proptosis include peri-implant inflammation, capsular hemorrhage, gelatin film cyst, implant infection, sino-orbital fistula, intraorbital sinus mucocele, and carotid-cavernous fistula. We describe the treatment of each case individually; in most cases, the implant was removed. All 12 patients had a satisfactory outcome after treatment. CONCLUSIONS: Proptosis presenting 2 months or more after orbital floor fracture is rare. We classify the origin of late proptosis into three groups: implant, sinus, and neurovascular. We describe the diagnosis and management of this unusual complication. PMID- 7772318 TI - The effect of intradermal corticosteroids on skin flap edema. AB - OBJECTIVE: To validate a model for skin flap edema in the piglet and determine whether intraoperative and postoperative intradermal corticosteroids reduce the edema created. DESIGN: Prospective, randomized, matched-control animal model. SETTING: Animal laboratory. PARTICIPANTS: Twenty-five weight-matched purebred Yorkshire piglets. INTERVENTION: Intraoperative and postoperative injections of intradermal triamcinolone. MAIN OUTCOME MEASURED: Flap edema. RESULTS: A reproducible skin flap edema model was validated in the piglet. Intraoperative intradermal corticosteroids decreased flap edema but postoperative corticosteroids did not. CONCLUSION: Clinical improvement in skin flap and supratip fullness may result from mechanisms other than edema. PMID- 7772319 TI - The effect of propofol on hematoma formation in rhytidectomy. AB - Significant surgical advances in face-lift surgery have evolved over the years, including wider flap undermining, the development of the superficial musculoaponeurotic system as a separate layer, and appropriate platysmal and coronal procedures. These more radical concepts offer improved results, but they may be associated with more complications, the most frequent being hematoma formation. A retrospective study of 386 patients was undertaken over a period of 5 years. Patients were separated into two groups: those that were sedated with a drug combination of diazepam, meperidine hydrochloride, and methohexital sodium; and those sedated with propofol. Patients sedated with propofol were more than twice as likely to develop a hematoma than those sedated with the other drug regimen. Although the hematoma rate with propofol is similar to that reported with other drugs, this increased risk must be carefully considered when one is choosing an anesthetic for rhytidectomy. PMID- 7772320 TI - Reduction of tissue edema by microdialysis. AB - OBJECTIVE: This is the first report (to our knowledge) of the use of tissue microdialysis to reduce tissue edema. In this study, a hyperosmotic solution was perfused through microdialysis catheters, allowing direct treatment of interstitial edema by osmosis. DESIGN: First, the catheter and perfusate characteristics were tested in vitro. A physiologic, controlled trial was then performed, with two outcome variables: osmolarity of the effluent and tissue water content. SUBJECTS: Twenty male Sprague-Dawley rats. One rat was withdrawn. INTERVENTIONS: Tissue microdialysis catheters were implanted in the rats. The control side of the animals was not perfused. The experimental side was perfused for 9 hours. RESULTS: Osmolarity of the perfusate was reduced 16.5 mOsm after passing through the catheter, indicating that fluid was removed from the tissue. Tissue edema was reduced by an average 1.8 mL of fluid per 100 g of wet tissue. CONCLUSIONS: Tissue microdialysis removed tissue fluid and reduced edema. This treatment may have a beneficial effect on edematous tissues. Potential use and limitations of this therapeutic modality are discussed. PMID- 7772321 TI - Ketorolac (Toradol) and acute random-pattern skin flap survival in rat. AB - OBJECTIVE: To assess the efficacy of sustained postoperative intramuscular ketorolac tromethamine (Toradol) at analgesic levels in the augmentation of acute, random-pattern skin flaps in rat. DESIGN: Prospective, randomized, placebo controlled, animal trial. SETTING: Animal research laboratory, School of Medicine, Oregon Health Sciences University, Portland. SUBJECTS: Forty-four adult male Sprague-Dawley rats (260 to 280 g). INTERVENTIONS: Twenty-two treatment animals underwent modified McFarlane random-pattern skin flaps followed immediately by intramuscular loading doses of ketorolac. Treatment animals were then maintained on a regimen of intramuscular ketorolac using a three times a day dosing schedule for 14 days postoperatively. Twenty-two control animals underwent identical modified McFarlane random-pattern skin flaps and were given equivalent volumes of intramuscular saline on the same dosing schedule for the 14-day treatment period. MAIN OUTCOME MEASURES: Postmortem measurements of skin flap ischemia (expressed as a percentage of total flap surface area) were performed for both treatment and control animals by three independent, non-blinded observers using the acetate tracing technique. Both pooled and individual data were statistically analyzed using personal computer software. RESULTS: Forty three of the 44 animals successfully completed the experimental trial. One animal in the treatment group died on postoperative day 3 of unknown causes. During the study period, one postoperative hematoma was detected in both the treatment and control groups. The mean percentage of skin flap ischemic necrosis observed in control animals (35.4%) was consistently less than that measured in the treatment group (36.4%). However, the difference in ischemic flap necrosis between control and treatment groups was not statistically significant (P = .6919). CONCLUSIONS: Comparatively high-dose intramuscular ketorolac failed to augment acute, random pattern skin flap survival in rat when initiated in the immediate postoperative period. Complications of prolonged, intramuscular ketorolac were not observed in this trial. Further studies using preoperative initiation of drug therapy may help to clarify the true efficacy of ketorolac in flap augmentation. PMID- 7772322 TI - Treatment of experimental frostbite with pentoxifylline and aloe vera cream. AB - OBJECTIVE: To compare the therapeutic effects of systemic pentoxifylline and topical aloe vera cream in the treatment of frostbite. DESIGN: The frostbitten ears of 10 New Zealand white rabbits were assigned to one of four treatment groups: untreated controls, those treated with aloe vera cream, those treated with pentoxifylline, and those treated with aloe vera cream and pentoxifylline. MAIN OUTCOME MEASURES: Tissue survival was calculated as the percent of total frostbite area that remained after 2 weeks. RESULTS: The control group had a 6% tissue survival. Tissue survival was notably improved with pentoxifylline (20%), better with aloe vera cream (24%), and the best with the combination therapy (30%). CONCLUSION: Pentoxifylline is as effective as aloe vera cream in improving tissue survival after frostbite injury. PMID- 7772323 TI - Cardiac complication from use of cocaine and phenylephrine in nasal septoplasty. AB - Cocaine hydrochloride is widely used as a topical anesthetic for otolaryngologic surgery. Cardiovascular complications, including myocardial injury, are well documented side effects of illicit cocaine use. We describe a 23-year-old woman without coronary artery disease who had an acute non-Q-wave myocardial infarction and stunned myocardium after receiving topical phenylephrine hydrochloride and cocaine anesthesia for elective nasal septoplasty. These cases are rare; however, we hope to heighten the awareness of the potential lethal complications of using cocaine, phenylephrine, or the combination of both as topical anesthetics in otolaryngologic practice. PMID- 7772324 TI - Clear cell odontogenic carcinoma. A clinicopathologic analysis. AB - Clear cell odontogenic tumor is a rare neoplasm of the jaws that histologically may be confused with metastatic renal cell carcinoma. A review of 17 cases revealed that these tumors are aggressive, with a tendency to recur locally after surgery; they also may metastasize both regionally and distantly. There is a marked female predilection, and most cases are discovered during the fifth to seventh decades of life. Seventy percent occur in the mandible, appearing as poorly marginated radiolucencies. We conclude that this tumor is malignant and should be referred to as clear cell odontogenic carcinoma; it requires an aggressive surgical approach. PMID- 7772326 TI - Pathologic quiz case 1. Chondrosarcoma of the mandible. PMID- 7772325 TI - The use of interferon alfa-2a for life-threatening hemangiomas. AB - Hemangiomas are the most common benign neoplasm in the neonatal period. While most small hemangiomas involute spontaneously, up to 20% may grow to a massive size and never completely involute. Massive hemangiomas are also frequently associated with life-threatening complications, such as airway obstruction, platelet trapping (Kasabach-Merritt syndrome), and high-output heart failure. The use of interferon alfa-2a for the treatment of massive hemangiomas not responsive to traditional therapy has recently been reported. We present the successful use of interferon alfa-2a in a series of five patients with massive hemangiomas complicated by airway compromise, congestive heart failure, need for tracheotomy, Kasabach-Merritt syndrome, and failure to thrive, despite traditional therapy. PMID- 7772327 TI - Pathologic quiz case 2. Moderately differentiated neuroendocrine carcinoma of the larynx. PMID- 7772328 TI - Current concepts in the treatment of sinusitis. PMID- 7772329 TI - Botulinum toxin. PMID- 7772330 TI - Sex and familial sinistrality differences in cognitive abilities. AB - Cognitive functioning was assessed in 69 left-handed males and females with a positive family history of left-handedness and in 77 left-handed and 55 right handed males and females without familial left-handedness. Compared to females, males performed better on numerical reasoning and on two visuospatial tasks involving spatial manipulations (Figure Rotation and Surface Development). Within the group of left-handers, the multivariate effect for Familial Sinistrality was significant. Left-handers with familial left-handedness exhibited better scores on numerical reasoning, on verbal reasoning, and on two visuospatial tasks involving visual closure (Hidden Figures, Picture Completion) than did left handers without left-handed relatives. The nonfamilial left-handers also exhibited lower scores on both inductive reasoning tasks when they were compared to their right-handed counterparts. The outcome runs contrary to the prevalent conclusion that left-handers with left-handed relatives are more likely to exhibit lower performances on visuospatial tasks than left-handers without such relatives. PMID- 7772331 TI - A model and diagnostic measures for response time series on tests of concentration: historical background, conceptual framework, and some applications. AB - Based upon classical hypotheses about accumulating mental fatigue and distraction and its effect on response times, put forward in late 19th and early 20th century papers, a mathematical model is proposed for response times on tests of speed and concentration. The model assumes the random occurrence of very short distractions during information processing. It explains fluctuation and the increasing trend in response times on successive equivalent task units and leads to some simple diagnostic RT measures of speed and concentration as alternatives to the mean RT. A review is given of several experimental applications of the model, with subjects with and without concentration problems, using cancellation and digit addition tasks. The results demonstrate the potential usefulness of the model and the diagnostic measures derived from it. As predicted by the model, prolonged task performance yields an increasing trend in RT mean and variance that can be strongly reduced by giving very short resting periods very frequently, and to a lesser extent also by task alternation, but not by simply motivating the subjects to concentrate. Some practical implications for the administration and scoring of tests of speed and concentration are discussed, as well as limitations of the present results and the complementary relation of our approach to popular ones such as "stage analysis." PMID- 7772332 TI - Item and order recognition memory in subjects with hypoxic brain injury. AB - Subjects with hypoxic brain injury resulting in significant cell loss in the hippocampus but not the parahippocampal gyrus or temporal lobes and normal control subjects were tested for memory impairments. The Denman Memory Scale was given to all subjects as a baseline memory assessment. All subjects were then tested for item and order recognition memory for lists of six words, pictures, abstract pictures, spatial locations, and motor responses. Results indicated that hypoxic subjects are impaired compared to control subjects on the Denman memory scale for verbal, non-verbal, and full-scale memory quotients. In addition, results indicated that compared to control subjects, hypoxic subjects displayed item and order recognition deficits for words, pictures, abstract pictures, and spatial locations. A recency effect for item recognition of abstract pictures, spatial locations, and hand positions was found. For motor response order recognition, both primacy and recency effects were found, with deficits in performance for the middle items of the list. It appears that subjects with hypoxic brain injury in the face of severe memory deficits for words, pictures, abstract pictures, and spatial locations display residual capacity for remembering the last items for spatial locations, abstract designs, and hand positions. Hypoxic subjects also display residual capacity for remembering motor responses using episodic or data-based memory. PMID- 7772333 TI - Frontal lobe dysfunction in schizophrenia and obsessive-compulsive disorder: a neuropsychological study. AB - Converging evidence suggests there is a specific role of dorso-lateral-prefrontal cortex (DLPC) in schizophrenic disorders and of orbito-frontal cortex (OFC) in obsessive-compulsive disorder (OCD). Here, 25 schizophrenic and 25 OCD patients were evaluated with Wisconsin Card Sorting Test and Object Alternation Test; neuropsychological tools sensitive to DLPC and OFC damage, respectively; and compared with 25 subjects of a control group. Moreover, they all underwent Weigl's Sorting Test and the Word Fluency Test to assess global frontal functioning. The results indicated a DLPC deficit in schizophrenia and an OFC involvement in OCD. These data suggest that functional disorders of the central nervous system can be explored with neuropsychological instruments. PMID- 7772334 TI - Progressive ideomotor apraxia: evidence for a selective impairment of the action production system. AB - We report a patient with slowly progressive bilateral limb apraxia associated with an asymmetrical focal degenerative process of the parietal lobes. Clinical assessment of praxis production suggested a striking deficit in controlling the spatiotemporal attributes of purposeful skilled limb movements, consistent with ideomotor apraxia. The precise nature of the action production impairment was further defined by objective three-dimensional computergraphic analysis of transitive movements which demonstrated significant kinematic deficits in spatial accuracy, timing, spatiotemporal coupling, and joint coordination. Gesture comprehension and discrimination were spared. Furthermore, detailed evaluation of the conceptual praxis system revealed that despite an almost complete inability to perform transitive movements accurately, abstract knowledge of tool function and action was remarkably well preserved. The critical dissociation between intact conceptual knowledge of action and impaired movement execution documented in this case points to a fundamental competence/performance dichotomy in apraxia and provides empirical support for cognitive models of praxis that divide the action system into distinct conceptual and production subcomponents. Within this theoretical framework, our patient's severe ideomotor apraxia is interpreted to represent a selective disruption of the action production system. PMID- 7772335 TI - As the twig is bent: the biology and socialization of gender roles in women. AB - The present study supports the view that biological predisposition interacts with perceived parental influences to affect cross-gender role identity. Geschwind and colleagues have identified two patterns of brain organization (anomalous and standard dominance) assessed through individual and familial handedness. Anomalous dominant women who perceived their parents as definitely giving them permission for cross-gender behavior demonstrated high masculine/low feminine characteristics on the Bem Sex Role Inventory. The cross-gender role identity in this group differed significantly from the traditional gender role identity found in all other groups of females (including anomalous dominant women whose parents were perceived as less permissive and the women with standard dominance reporting both styles of parenting. PMID- 7772336 TI - Production of live offspring with predicted genotypes using PCR-RFLP analysis of polar bodies from mouse oocytes. AB - Accurate identification of genotypes in gametes and early embryos could facilitate the efficient production of offspring with desirable traits. This study demonstrates the feasibility of producing offspring with predictable genotypes from micromanipulated mouse oocytes. The Polymerase Chain Reaction (PCR) was used to amplify genes in the IA subregion of the major histocompatibility complex of the mouse. The validity of the approach was demonstrated in experiment 1 with IA haplotypes of unfertilized mouse ova amplified via PCR and distinguished by restriction fragment length polymorphism (RFLP) analysis. In experiment 2, fertilized oocytes were micromanipulated to remove the first and second polar bodies, which were then genotyped by validated PCR-RFLP procedures. Primary oocytes of heterozygous females contain two copies of each of the different alleles. Following meiosis I and II, the genotype of the ovum was predicted by subtracting the alleles observed in micromanipulated polar body samples. Sixty-two fertilized ova were micromanipulated and transferred to recipient females resulting in 27 live offspring (44%). The correct maternal contribution to the embryonic genotype was predicted in 19 of 27 (71%) offspring as confirmed by PCR-RFLP analysis of DNA from pup tails. Predicted genotypes of two pups were not confirmed (7%), whereas no prediction could be made in six cases (22%). PMID- 7772337 TI - Poly (A) binding protein is bound to both stored and polysomal mRNAs in the mammalian testis. AB - RNA-binding proteins that bind to the 3' untranslated region of mRNAs play important roles in regulating gene expression. Here we examine the association between the 70 kDa poly (A) binding protein (PABP) and stored (RNP) and polysomal mRNAs during mammalian male germ cell development. PABP mRNA levels increase as germ cells enter meiosis, reaching a maximum in the early postmeiotic stages, and decreasing to a nearly nondetectable level towards the end of spermatogenesis. Most of the PABP mRNA is found in the nonpolysomal fractions of postmitochondrial extracts, suggesting that PABP mRNA is either inefficiently translated or stored as RNPs during spermatogenesis. Virtually all of the testicular PABP is bound to either polysomal or nonpolysomal mRNAs, with little, if any, free PABP detectable. Analysis of several specific mRNAs reveals PABP is bound to both stored (RNP) and translated forms of the mRNAs. Western blot analysis and immunocytochemistry indicate PABP is widespread in the mammalian testis, with maximal amounts detected in postmeiotic round spermatids. The presence of PABP in elongating spermatids, a cell type in which PABP mRNA is nearly absent, suggests that PABP is a stable protein in the later stages of male germ cell development. The high level of testicular PABP in round spermatids and in mRNPs suggests a role for PABP in the storage as well as in the subsequent translation of developmentally regulated mRNAs in the mammalian testis. PMID- 7772338 TI - Activin beta A subunit is expressed in bovine oviduct. AB - It is evident that members of several growth factor families are actively involved in embryogenesis from its earliest phases. Several reports also indicate the oviduct as a possible source of growth factors, suggesting an active role of this organ in mammalian embryonic development. The aim of this study was to investigate the presence of activin/inhibin subunits in bovine oviduct since activin is a well-characterised morphogen in amphibian development. The presence of transcripts for alpha, beta A, and beta B subunits was investigated by analysing oviduct epithelial cells mRNA with reverse transcription-polymerase chain reaction (RT-PCR). Moreover, antisera specific for the three subunits were used for the Western blot analysis of the proteins secreted by oviduct epithelial cells in vitro and for their immunohistochemical localisation in different oviductal regions. Oviduct epithelial cells expressed only the beta A-subunit gene. Immunoreactive material was present among in vitro secreted proteins, indicating that the transcript is translated into a polypeptide that has been localised in the epithelium of both the ampullary and isthmic tract of the organ. Consistent with these results, the antisera for the alpha and beta B subunits did not recognise any specific antigen either among secreted proteins or in the sections. These results indicate that beta A subunit gene is expressed in bovine oviduct epithelial cells, and the protein is secreted in vitro and can be found along the whole extension of the organ. In the absence of alpha or beta B subunits, this suggests that activin A is present in bovine oviduct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772340 TI - Localization of fibrillarin and nucleolin in nucleoli of mouse preimplantation embryos. AB - The localization of fibrillarin and nucleolin in the nuclei of mouse two-cell, four-cell, and eight-cell embryos has been studied using immunofluorescent staining with specific antibodies. In all of these cleavage stages, both antigens were associated exclusively with the peripheral region of the nucleolus precursor bodies (NPBs). The original speckled fluorescent staining pattern in the early two-cell stage was progressively changed into a continuous fluorescent-positive layer localized in the cortex of the NPBs in the four-cell embryos. The compact central area of NPBs was never stained. Both proteins were colocalized in the same substructures of developing nucleoli. In order to analyze the interaction of chromatin with NPBs, DNA structures were specifically immunolabelled. At the time of resumption of nucleolar transcription (in the two-cell mouse embryo), DNA was detected at the periphery of, but not penetrating into, NPBs. Our results confirm the view that the cortical region of NPBs could represent a nucleolonemal area involved in the resumption of nucleolar transcription in the early mouse embryo. PMID- 7772339 TI - Factors involved in nuclear reprogramming during early development in the rabbit. AB - Mechanisms of nuclear reprogramming and assessment of potential malfunctions that could be deleterious for development were evaluated in rabbit zygotes, parthenotes, and nuclear transfer embryos by analysis of DNA replication, nucleolar fibrillarin label, and localization of nuclear material reactive to the MPM-2 antibody. Nuclear transfer embryos were derived from G1/early S-phase donor nuclei and MII oocytes. In nuclear transfer embryos, DNA rereplication was likely to have occurred because label was incorporated, possibly in the centromeric regions of the chromosomes, prior to premature chromosome condensation and again following pronuclear formation. In parthenotes, DNA replication began very late in the cell cycle, which may be due to deficiencies in the artificial activation stimulus. The presence of fibrillarin label in the nucleolus was used as an indication of nucleolar transcriptional activity. Fibrillarin label was absent in embryos of all types up to the 16-32-cell stage. Although fibrillarin reappeared in nuclear transfer and parthenote embryos at the appropriate stage, not all blastomeres showed label indicating impaired development in these embryos. Labelling of phosphorylated epitopes by MPM-2 antibody showed a change in pattern of labelling during early development. Early cleavage stage embryos did not exhibit labelling over the spindle poles as did blastomeres from 32-cell embryos and tissue culture cells. All cell types exhibited labelling during interphase as dots located primarily over the nucleus in blastomeres from 32-cell embryos and in tissue culture cells, together with cytoplasmic label in embryos at early cleavage stages. Nuclear transplant embryos had a normal pattern of MPM-2 label. In contrast, the appearance of MPM-2 label in parthenotes depended on the type of calcium stimulation. These results demonstrate defects in DNA synthesis, nucleolar activity, and specific phosphorylation events, likely resulting from an improper activation stimulus and chromosome condensation in the transplanted nucleus. PMID- 7772341 TI - Initial culture behaviour of rat blastocysts on selected feeder cell lines. AB - To increase our understanding of rat embryos in culture and to attempt the isolation of blastocyst-derived cell lines, we examined the initial growth behaviour of rat blastocysts from four strains of rat on four different feeder cell layers. The feeders used were a continuous cell line of murine embryonic fibroblasts (STO), primary mouse (MEF) or primary rat (REF) embryonic fibroblasts, and a continuous cell line of rat uterine epithelial cells (RUCs). A medium that gave optimum plating efficiencies for murine ES cells was used in the rat embryo culture. Each culture system allowed hatching and attachment of the blastocysts, that is, the behaviour was similar on each feeder and each strain for the first 2 days in culture. Subsequently, there was a rapid differentiation of the Inner Cell Mass (ICM) cells on fibroblastic feeder cell layers (STO > MEF > REF), and this was generally complete after 3-6 days in primary culture. On RUCs, the ICM was found to increase in size without differentiation up to and including day 4 and in some cases longer. Embryo-derived cells were obtained by disaggregating and passaging ICMs on REF and RUC feeders. Rounded, refractile, and epithelial-like cells were isolated on REF and colonies of ES-like cells on the RUCs. The ES-like cells were positive for expression of alkaline phosphatase and stage-specific embryonic-antigen 1. This is an important first step towards the derivation and culture of pluripotent ES cells from the rat. PMID- 7772342 TI - DNA synthesis and pronucleus development in pig zygotes obtained in vivo: an autoradiographic and ultrastructural study. AB - Porcine zygotes flushed from oviducts 48, 52, 56, 60, or 64 hr after hCG were incubated 30 min in 3H-thymidine, transferred to nonradioactive medium for 2 hr, and incubated for 30 min with 14C-thymidine. After this procedure, ova were prepared (i.e., at 51, 55, 59, 63, or 67 hr after hCG) for autoradiography and ultrastructural observations, respectively. The first autoradiographic labelling, i.e., DNA synthesis, was observed at 56-56.5 hr after hCG, while the latest labelling was seen at 60-60.5 hr. At 51 hr after hCG, formation of the pronuclear envelope was observed, while no nucleolus precursor bodies or prestages to these structures were found. At 55 hr a few clusters of small electron-dense granules were observed, together with condensed chromatin in the pronuclei. At 59 hr the apposed regions of both pronuclei contained nucleolus precursor bodies and condensed chromatin, in close contact with both clusters of small granules and clusters of an additional category of large granules and the nuclear envelope. Additionally, large accumulations of the small granules were found in the vicinity of similarly sized accumulations of the large granules without chromatin association. At 63 hr the spherical accumulations of large granules on some occasions presented a central vacuole, and condensed chromatin and clusters of small granules were attached to its periphery. Within the vacuole, electron-dense material was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772343 TI - PRINS as a method for rapid chromosomal labeling on human spermatozoa. AB - Direct in situ labeling of human spermatozoa was performed using the PRINS method. This technique is based on annealing of specific oligonucleotide primers, and subsequent primer extension by a Taq DNA polymerase. The reaction was carried out on a programmable temperature cycler, and labeling was obtained in a 1-hr reaction. The method was successfully tested with specific primers for chromosomes 13, 16, and 21. This suggests that PRINS may be a fast and reliable technique for detecting aneuploidies. PMID- 7772344 TI - Cumulus cell function during bovine oocyte maturation, fertilization, and embryo development in vitro. AB - Several contemporary micromanipulation techniques, such as sperm microinjection, nuclear transfer, and gene transfer by pronuclear injection, require removal of cumulus cells from oocytes or zygotes at various stages. In humans, the cumulus cells are often removed after 15-18 hr of sperm-oocyte coincubation to assist the identification of the fertilization status. This study was designed to evaluate the function of cumulus cells during oocyte maturation, fertilization, and in vitro development in cattle. Cumulus cells were removed before and after maturation and after fertilization for 0, 7, 20, and 48 hr. The cumulus-free oocytes or embryos were cultured either alone or on cumulus cell monolayers prepared on the day of maturation culture. Percentages of oocyte maturation, fertilization, and development to cleavage, morula, and blastocyst stages and to expanding or hatched blastocysts were recorded for statistical analysis by categorical data modeling (CATMOD) procedures. Cumulus cells removed before maturation significantly reduced the rate of oocyte maturation (4-26% vs. 93 96%), fertilization (0-9% vs. 91-92%), and in vitro development at all stages evaluated. Cumulus cells removed immediately prior to in vitro fertilization (IVF) or 7 hr after IVF reduced the rates of fertilization (58-60% and 71%, respectively, vs. 91-92% for controls), cleavage development (40-47% and 53-54% vs. 74-78% for controls), and morula plus blastocyst development (15% and 24% vs. 45%, P < 0.05). Cumulus cell co-culture started at various stages had no effect on fertilization and cleavage development but significantly improved rates of embryo development to morula or blastocyst stages (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772345 TI - Identification of heterotrimeric G proteins in human sperm tail membranes. AB - Heterotrimeric G proteins play important roles as signal transducing components in various mammalian sperm functions. We were interested in the distribution of G proteins in human sperm tails. Prior to membrane preparation, spermatozoa were separated from contaminating cells which are frequently present in human ejaculates. Enriched human sperm tail membranes were generated by using hypoosmotic swelling and homogenization procedures. Antisera against synthetic peptides were used to identify G proteins in immunoblots. AS 8, an antiserum directed against an amino acid sequence that is found in most G protein alpha subunits, and A 86, which detects all known pertussis toxin-sensitive alpha subunits, reacted specifically with a 40-kDa protein. Antisera against individual G protein alpha-subunits failed to detect any specific antigens in enriched tail membranes. AS 36, recognizing the beta 2-subunit of G proteins, identified a 35 kDa protein in sperm tail membranes. Antisera against the 36-kDa beta 1-subunit did not detect any relevant proteins in the membrane fraction. Neither G protein alpha-subunits nor G protein beta-subunits were found in the cytosol. ADP ribosylation of spermatozoal membrane or cytosolic proteins revealed no pertussis toxin-sensitive alpha-subunits. However, membrane preparations of nonpurified human spermatozoa contained alpha i2 subunits, as shown immunologically and by ADP ribosylation; they most probably derived from somatic cells which are frequently present in human ejaculates. Our results stress the fact that spermatozoa need to be purified before sperm membrane preparation to avoid misinterpretations caused by contaminating cells. Furthermore, we suggest that G proteins in membranes of human sperm tails belong to a novel subtype of G protein alpha-subunits; the putative beta-subunit was identified as a beta 2-subunit. PMID- 7772346 TI - Activation of a Gi protein in digitonin/cholate-solubilized membrane preparations of mouse sperm by the zona pellucida, an egg-specific extracellular matrix. AB - Mammalian sperm possess guanine nucleotide-binding regulatory proteins (G proteins) that are involved in signal transduction pathways leading to zona pellucida (ZP)-mediated acrosomal exocytosis. We have previously examined ZP-G protein dynamics in mouse sperm homogenates, as well as cell-free membrane preparations, and our data support the existence of ZP receptor-G protein complexes in sperm membranes. However, the composition of this complex has not been identified due to experimental limitations of the membrane preparations. In the present study, a detergent-solubilized preparation from mouse sperm membranes that retained the signaling properties of cell homogenates and cell-free membrane preparations was developed using buffers containing digitonin and cholate. GTP gamma S, a poorly hydrolyzable analogue of GTP, bound to these solubilized preparations in a specific and concentration-dependent fashion that reached saturation at 100 nM. Incubation of this solubilized membrane preparation with heat-solubilized ZP resulted in an increase in specific GTP gamma S binding in a concentration-dependent manner, with a maximal response at 4-6 ZP/microliters. Mastoparan (50 microM) increased GTP gamma S binding to levels similar to that seen with solubilized ZP. Mastoparan plus ZP stimulated GTP gamma S binding to the same extent as mastoparan or ZP alone. Pertussis toxin completely inhibited ZP-stimulated GTP gamma S binding and decreased mastoparan-stimulated GTP gamma S binding by 50-60%. Purified ZP3, the ZP component that possesses quantitatively all of the sperm binding and acrosomal exocytosis-inducing activities of the intact ZP, stimulated GTP gamma S binding to an extent similar to that of solubilized ZP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772347 TI - Effects of stimulators of protein kinases A and C and modulators of phosphorylation on plasminogen activator activity in porcine oocyte-cumulus cell complexes during in vitro maturation. AB - Effects of phorbol myristate acetate (PMA), dibutyryl cyclic AMP (dbcAMP), 6 dimethylaminopurine (6-DMAP), and okadaic acid (OA) on plasminogen activator (PA) activity in porcine oocyte-cumulus cell complexes (POCC) in vitro were determined. Cumulus cell-enclosed oocytes were collected from 1-4 mm antral follicles and cultured in TCM-199 with 0.3% polyvinylpyrrolidone for 48 hr. PA activities in POCC were quantified using SDS-PAGE, casein-agar zymography, and densitometry. Two plasminogen-dependent lytic zones (93-96 kD and 71-79 kD) were observed in POCC. Addition of amiloride to the zymography, a competitive inhibitor of urokinase-type PA, failed to reduce activities in either zone, suggesting that the 71-79 kD band is a tissue-type PA (tPA) and the 93-96 kD band is possibly a tPA-inhibitor complex. Changes in PA activity due to the various treatments were expressed relative to the PA activity in 40 POCC. Increasing dbcAMP increased PA (P < 0.05) activity in dose-dependent fashion, whereas 6-DMAP and 10 and 100 ng/ml PMA inhibited (P < 0.05) PA activity. PA activity increased (P < 0.05) in POCC treated with up to 25 nM OA; however, activity decreased (P < 0.05) at concentrations > 75 nM. Treatment with 25 nM OA also induced the expression of an amiloride-sensitive PA (49-52 kD). Germinal vesicle breakdown and progression to metaphase II were inhibited (P < 0.05) by 2.5 mM dbcAMP and 2 mM 6-DMAP, whereas 100 ng/ml PMA and 25 nM OA inhibited (P < 0.05) only progression to metaphase II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772348 TI - Atrial natriuretic peptide: a chemoattractant of human spermatozoa by a guanylate cyclase-dependent pathway. AB - Atrial natriuretic peptide (ANP), found in mammalian ovarian granulosa cells and oocytes (Kim et al., 1992, 1993), induces the human acrosome reaction (Anderson et al., 1994). The purpose of the present study was to determine whether ANP, as egg-derived peptides from sea urchins, can act as a chemoattractant to human spermatozoa. Small lengths of capillary tubing that contained different concentrations of ANP were suspended over a suspension of washed spermatozoa. The number of spermatozoa that entered the tubing was determined. More than twice the number of spermatozoa moved into the tubing that contained a maximally effective concentration of ANP, as compared with tubing that contained only medium. The concentration of ANP that produced a half-maximal effect was 0.7 nM. The effect was blocked by LY83583, an inhibitor of guanylate cyclase. ANP produced more than a twofold increase in the rate of cGMP formation, an effect that was blocked by LY83583. Human ANP (5-27), a fragment of the intact peptide, had no chemoattractant activity. These findings suggest that a specific sperm receptor exists for the chemoattractant activity of ANP that is associated with guanylate cyclase. The chemoattractant activity of ANP is independent of the presence of extracellular calcium ions and is independent of the action of ANP as a stimulus of the acrosome reaction. There is no association between the chemoattractant activity of follicular fluid and the follicular fluid concentration of ANP. These data suggest that factors besides ANP are responsible for the chemoattractant activity of follicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772349 TI - Changes in dopamine uptake and developmental effects of dopamine receptor inactivation in the sea urchin. AB - [3H]-dopamine ([3H]-DA) uptake was measured in the presence or absence of the catecholamine uptake inhibitor nomifensine in both unfertilized and fertilized eggs. Specific [3H]-DA uptake depended on time and [3H]-DA concentration; it was high in unfertilized eggs, declined 20-30 min after fertilization, and rose again during cleavage. Irreversible inactivation of dopamine receptors by N ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) resulted in a complete loss of sensitivity of egg adenylate cyclase to dopamine stimulation. In fertilized eggs treated with EEDQ for 1 hr, restoration of adenylate cyclase activity sensitive to dopamine stimulation could be observed 4 hr after the end of treatment, thus suggesting the appearance of new dopamine receptors in cleaving eggs. Short-term EEDQ treatment on unfertilized eggs, although not impairing fertilization, resulted in cleavage inhibition; the same treatment carried out soon after fertilization, on the other hand, elicited no effect on development. On the contrary, in embryos subjected to continuous treatment with EEDQ, development was impaired independent of the stage at which the treatment was started. PMID- 7772350 TI - Efficient production of transgenic cattle by retroviral infection of early embryos. AB - Production of transgenic cattle by microinjection of DNA has been difficult and costly. To explore an alternative method, one- to four-cell bovine embryos were exposed to a replication-defective retrovirus by microinjection of retrovirus producer cells into the perivitelline space. Embryos were cultured in vitro for 3 4 days, then transferred to recipient cows for further development. Thirteen of 22 embryos recovered at 15 days gestation and each of four fetuses recovered at 90 days gestation were transgenic. Fetuses harbored between 2 and 12 proviruses, and within each fetus, identical patterns of integration were observed in seven tissues tested. Estimates of the number of proviruses per cell suggested that in three of the four fetuses, most, and possibly all, cells were transgenic. This technique should facilitate application of transgenic technology to cattle and other agriculturally important species. PMID- 7772351 TI - Parturient's posture during epidural puncture affects the distance from skin to epidural space. AB - STUDY OBJECTIVE: To assess the factors affecting the distance from skin to epidural space. DESIGN: Prospective observational study of consecutive cases over a 2-year period. SETTING: Inpatient obstetric unit in a French university hospital. PATIENTS: 2,123 consecutive term parturients who received epidural anesthesia for cesarean section or epidural analgesia for labor and vaginal delivery. INTERVENTIONS: At the time of epidural puncture, the interspace used and the patient's posture (sitting or left lateral decubitus) were recorded, and the distance from the skin to the epidural space (DS-ES) was measured to the nearest 0.5 cm using a marked epidural needle. MEASUREMENTS AND MAIN RESULTS: The relationship between patient factors [height, weight, body mass index (BMI; weight/height2), presence of scoliosis] and technical factors (interspace, patient's posture at puncture) versus DS-ES was investigated using multiple regression analysis. DS-ES correlated positively with the parturient's weight and BMI. In addition, DS-ES was significantly greater when epidural puncture was performed in the lateral position as compared with the sitting position. CONCLUSION: Both the patient's weight and position during epidural needle placement are important factors influencing DS-ES. A change from the sitting to the lateral position may increase DS-ES, causing catheter dislodgment and consequent inadequate analgesia. Clinical studies relating DS-ES to inadequate analgesia must take these factors into account. PMID- 7772352 TI - Comparison of cardiovascular responses to airway management: fiberoptic intubation using a new adapter, laryngeal mask insertion, or conventional laryngoscopic intubation. AB - STUDY OBJECTIVES: To evaluate the circulatory effects of fiberoptic intubation with a newly developed mask adapter and to compare these effects with those obtained with a conventional laryngoscope and laryngeal mask airway with general anesthesia. DESIGN: Randomized study. SETTING: Operating room at a university hospital. PATIENTS: 30 ASA physical status I adult patients scheduled for minor elective surgery. INTERVENTIONS: A Macintosh laryngoscope was used for intubation in Group L (n = 10), a fiberoptic bronchoscope with newly developed mask adapter was used in Group FI (n = 10), and a laryngeal mask airway was used in Group LMA (n = 10). Anesthesia was induced with thiamylal, fentanyl, and vecuronium. Patients were manually ventilated for 4 minutes with sevoflurane. Then their tracheas were intubated with a laryngoscope or fiberoptic bronchoscope, or a laryngeal mask airway was inserted. MEASUREMENTS AND MAIN RESULTS: Blood pressure (BP) and heart rate (HR) were measured continuously. After intubation, the magnitude of change of both BP and HR was greatest in Group L, next highest in Group FI, and lowest in Group LMA. CONCLUSION: Fiberoptic intubation with general anesthesia using the newly developed mask adapter offers an advantage over the standard laryngoscope for patients in whom pressor response of intubation is potentially hazardous. PMID- 7772353 TI - High-frequency jet ventilation in endolaryngeal surgery. AB - STUDY OBJECTIVE: To describe the clinical experience with high-frequency jet ventilation (HFJV) of the lungs during endolaryngeal surgery and its effect on acid-base balance and capillary PO2 (PcO2), PCO2, central hemodynamics, and tracheobronchial mucous membrane. DESIGN: Evaluation of different modalities of HFJV. SETTING: Operating rooms and otolaryngology intensive care unit in a medical institute. PATIENTS: 218 patients undergoing elective endolaryngeal surgery. INTERVENTIONS: Patients receive HFJV through catheters with an inner diameter of 1.4 to 1.8 mm. Catheters were introduced orotracheally, nasotracheally, percutaneously, or through a fenestrated tracheostomy tube. Minute volume was based on body weight times 0.2, corrected for acid-base balance. MEASUREMENTS AND MAIN RESULTS: Intraoperative cardiac output, airway pressure, changes in tracheobronchial mucosa, and acid-base balance were monitored. HFJV changed central hemodynamics slightly and preserved gas exchange: PcCO2 remained within normal limits, while PcO2 increased. Use of thin catheters enhanced largyneal exposure and surgical manipulation. Percutaneous catheterization permitted resumption of HFJV in the event of laryngeal edema and inadequate spontaneous respiration after surgery. CONCLUSION: HFJV leads to optimal conditions for endolaryngeal surgery, reverses constant outflow of the respiratory gas mixture, prevents aspiration of tissue products and blood, and removes smoke from the operative site when using laser surgery. PMID- 7772354 TI - Postoperative analgesia and plasma levels after transdermal fentanyl for orthopedic surgery: double-blind comparison with placebo. AB - STUDY OBJECTIVE: To determine whether transdermal fentanyl can provide a significant component of postoperative analgesia. DESIGN: Randomized, double blind study. SETTING: Inpatient surgery in a university hospital. PATIENTS: 40 adult patients scheduled for orthopedic surgery with general anesthesia. INTERVENTIONS: 20 patients in each group had general anesthesia with propofol, isoflurane in nitrous oxide and oxygen (O2), and small boli of alfentanil or sufentanil. Preoperatively, the first group (F) received a transdermal therapeutic system fentanyl patch (75 micrograms/hr) for 72 hours, and the second group (P) received a placebo patch. Morphine was given postoperatively according to clinical necessity. MEASUREMENTS AND MAIN RESULTS: Morphine consumption, pain visual analog scale, and eventual sedation were assessed, as well as respiratory rate and blood pressure. Plasma fentanyl concentrations were determined. Only 11 Group F patients needed morphine compared with 19 Group P patients, and mean morphine dose was significantly lower in Group F. One Group F patient had decreased O2 saturation and intense sedation, necessitating administration of naloxone. The mean maximum plasma fentanyl concentration in Group F was 1.63 ng/ml. CONCLUSION: Efficacy of transdermal fentanyl for postoperative pain relief is shown, but intense respiratory depression is sometimes seen. PMID- 7772355 TI - Assessment of patient position for fiberoptic intubation using videolaryngoscopy. AB - STUDY OBJECTIVE: To compare laryngoscopic appearance obtained during flexible fiberoptic laryngoscopy with the patient's atlanto-occipital joint in the neutral and extended positions. DESIGN: Controlled clinical trial with each patient (in the neutral position) acting as his or her own control. SETTING: University teaching hospital. PATIENTS: 20 adult ASA physical status I and II patients, without anatomical airway abnormalities, undergoing elective surgical procedures. INTERVENTIONS: Fiberoptic laryngoscopy was performed on each patient with his or her atlanto-occipital joint in the neutral and extended positions. MEASUREMENTS AND MAIN RESULTS: Photographs of the laryngoscopic appearances were graded on a scale of 1 to 4 by a blinded observer according to the proportion of the laryngeal inlet visible. Atlanto-occipital extension improved laryngoscopic appearance in 14 cases and produced no change in the remaining 6. CONCLUSION: Atlanto-occipital extension is a useful maneuver during attempted fiberoptic intubation. PMID- 7772356 TI - The effects of oral droperidol versus oral metoclopramide versus both oral droperidol and metoclopramide on postoperative vomiting when used as a premedicant for strabismus surgery. AB - STUDY OBJECTIVE: To compare the efficacy of oral droperidol versus oral metoclopramide, or both oral droperidol and metoclopramide, on postoperative vomiting when used as a premedicant for strabismus surgery. DESIGN: Double-blind, randomized, prospective study. SETTING: Academic children's hospital. PATIENTS: 154 ASA physical status I and II ambulatory patients, ages 1 to 15 years, scheduled for strabismus surgery. INTERVENTIONS: Patients were randomly assigned to receive colored sugar water containing either droperidol 300 mcg/kg orally, metoclopramide 0.15 mg/kg orally, both droperidol 300 mcg/kg and metoclopramide 0.15 mg/kg orally, or no active ingredient (placebo group) as a premedicant. The premedications were given orally 1 to 1.5 hours prior to the operation. MEASUREMENTS AND MAIN RESULTS: Patients were analyzed for the number of episodes of vomiting from the time of their emergence from anesthesia through the first 24 hours postoperatively, including the convalescent period at home. Patients were also analyzed for length of hospital stay. There were no statistically significant differences between groups regarding age, premedication time, surgery time, or discharge time. Droperidol and droperidol-metoclopramide were significantly more effective (p < 0.012) than either the metoclopramide group or the placebo group in preventing postoperative nausea and vomiting following strabismus surgery. CONCLUSIONS: Our data suggest that oral droperidol 300 mcg/kg and the combination of oral droperidol 300 mcg/kg and metoclopramide 0.15 mg/kg are effective in reducing the frequency of vomiting within the first 24 hours after strabismus surgery. The combination of oral droperidol and oral metoclopramide is highly effective in reducing the frequency of vomiting postoperatively in strabismus ambulatory surgery patients (p = 0.017). This combination seems to represent an inexpensive alternative to the more costly ondansetron. PMID- 7772357 TI - Pharmacodynamics of rocuronium with and without prior administration of succinylcholine. AB - STUDY OBJECTIVES: To compare succinylcholine (S) and rocuronium (R) used for endotracheal intubation, and to assess the possible action of S on subsequently administered R. DESIGN: Double-blind, randomized, phase III study. SETTING: University Medical Center. PATIENTS: 24 ASA physical status I and II patients, ages 28 to 65, undergoing general anesthesia for abdominal procedures. INTERVENTION: Double-blind administration of R 600 mcg/kg (Group A) or S 1 mg/kg was achieved with open label R 150 mcg/kg. Standardized general anesthetic technique with sodium thiopental, fentanyl, and nitrous oxide in oxygen was administered. MEASUREMENTS AND MAIN RESULTS: Neuromuscular junction was tested by ulnar nerve stimulation and mechanomyograph. Intubation was attempted at 80% first twitch depression of train-of-four. Heart rate and blood pressure were recorded throughout. Onset times were 74 +/- 37 seconds for S and 130 +/- 46 seconds for R. Intubation times were 76 +/- 29 seconds for S and 85 +/- 23 seconds for R (no significant difference). Good to excellent intubation conditions were achieved in both groups. S given prior to R decreased onset time and increased duration of R, when compared with R given alone. No drug related cardiovascular events were noted. CONCLUSION: Rapid intubation conditions can be obtained after both S and R. Given its overall safety profile, R can be used when S is contraindicated, or in healthy patients with no apparent difficult airway, when procedures are expected to last more than 25 minutes. PMID- 7772358 TI - A lower solubility recommends the use of desflurane more than isoflurane, halothane, and enflurane under low-flow conditions. AB - STUDY OBJECTIVE: To determine whether the lower solubility of desflurane, over that of isoflurane, enflurane, and halothane, favors its use in low-flow anesthesia. DESIGN: Prospective clinical study. SETTING: Technical University of Munich. PATIENTS: 40 elderly (> or = 65 yrs), ASA physical status II and III surgical patients. INTERVENTIONS: All patients were anesthetized and received delivered concentrations (FD) of 4% desflurane, 1.5% isoflurane, 1.8% enflurane, or 0.9% halothane (n = 10 patients for each anesthetic) in a fresh gas inflow of 3 L/min (high-flow), until end-tidal target concentrations (FA) of 2% desflurane, 0.5% isoflurane, 0.6% enflurane, and 0.3% halothane were obtained. After 30 minutes, the inflow was decreased to 1 L/min (low-flow), and the FD and the inspired concentration (FI) were adjusted to maintain the target concentration. MEASUREMENTS AND MAIN RESULTS: The concentrations of the halogenated anesthetics, as well as nitrous oxide, oxygen (O2), and carbon dioxide, were measured in delivered gas at the common gas outlet and at the endotracheal tube connector. Transcutaneous O2 saturation, noninvasive blood pressure, and heart rate were also measured. During the first 30 minutes of high-flow administration, the target concentration was attained sooner with desflurane than with isoflurane, enflurane, or halothane (median levels: 4 min vs. 6 min, 8 min, or 10 min; p < 0.01). After the reduction of inflow to 1 L/min, FD had to be materially increased to maintain F1 and FA for the more soluble anesthetics, but not for desflurane. CONCLUSIONS: At low flows, FD provides a reasonable surrogate of F1 and FA for desflurane, but not for isoflurane, enflurane, or halothane. The rapid and predictable titrability of desflurane favors its safe use in low-flow technique. PMID- 7772359 TI - Comparative effects of lidocaine, esmolol, and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation. AB - STUDY OBJECTIVE: To compare the safety and efficacy of lidocaine, esmolol, and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: University-affiliated VA medical center. PATIENTS: 40 ASA physical status I and II patients undergoing electric surgery with general endotracheal anesthesia. INTERVENTIONS: Anesthesia was induced with thiopental sodium 5 mg/kg, and intubation was facilitated with vecuronium 0.15 mg/kg. Isoflurane (0.5% to 1%) and 50% nitrous oxide in oxygen were used for maintenance of anesthesia. In addition, patients received one of the following four study drugs intravenously (i.v.) prior to laryngoscopy: Group 1 (control) = saline 5 ml; Group 2 = lidocaine 1.5 mg/kg; Group 3 = esmolol 1.4 mg/kg; Group 4 = nitroglycerin 2 micrograms/kg. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP) and heart rate (HR) were recorded every minute for 20 minutes following induction of anesthesia. Following laryngoscopy and intubation, MAP increased significantly in all four treatment groups (control 49% +/- 19%, lidocaine 55% +/- 26%, esmolol 25% +/- 11%, nitroglycerin 45% +/- 21%) compared with preinduction baseline values. In the esmolol-pretreated patients, the increase in HR was significantly lower (20% +/- 3%) compared with the nitroglycerin (37% +/- 8%), lidocaine (52% +/- 8%), and control (29% +/- 4%) groups. CONCLUSIONS: Lidocaine 1.5 mg/kg i.v. and nitroglycerin 2 micrograms/kg i.v. were ineffective in controlling the acute hemodynamic response following laryngoscopy and intubation. Esmolol 1.4 mg/kg i.v. was significantly more effective than either lidocaine or nitroglycerin in controlling the HR response to laryngoscopy and intubation (p < 0.05). Esmolol also was significantly more effective than lidocaine in minimizing the increase in MAP (25% vs. 55%). PMID- 7772360 TI - Acquired QT interval changes and neck dissections. AB - STUDY OBJECTIVE: To determine if acquired long QT syndrome following right or left, radical or modified, neck dissections result in malignant arrhythmias or deaths. DESIGN: Prospective study. SETTING: Inpatient head and neck service of the Massachusetts Eye and Ear Infirmary. PATIENTS: 69 patients who underwent extensive neck surgery, without congenital long QT syndrome, medications known to prolong the QT interval, preoperative ventricular arrhythmias, or electrolyte abnormalities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative electrolytes were evaluated. Preoperative and postoperative electrocardiograms and QT intervals were evaluated. Continuous intraoperative and 10- to 12-hour postoperative monitoring of lead II or V5 were evaluated. Twenty six patients (Group 1) underwent either right radical neck dissection or modified right radical neck dissection, 25 patients (Group 2) underwent either left radical neck dissection or modified left neck dissection, and 18 patients (Group 3) underwent extensive neck surgery without radical or modified neck dissection. Postoperatively, 38 patients (19 Group 1, 11 Group 2, and 8 Group 3 patients) developed a QT interval corrected for heart rate (QTc) of greater than 440 milliseconds. Repeated measures analysis of variance, comparing preoperative and postoperative QTc showed a statistically significant preoperative to postoperative change, but no significant difference among the three groups. No malignant arrhythmias or deaths were recorded in any of the three groups. CONCLUSIONS: Acquired long QT syndrome following radical neck dissection, without congenital, metabolic, or pharmacologic disturbance, is unlikely to trigger malignant arrhythmias, as previously reported for right radical neck dissection. PMID- 7772361 TI - Prevention of emesis after strabismus repair in children: a prospective, double blinded, randomized comparison of droperidol versus ondansetron. AB - STUDY OBJECTIVE: To compare the effectiveness of ondansetron with droperidol in preventing postoperative emesis in children after strabismus repair. DESIGN: Randomized, double-blind study. PATIENTS AND SETTING: 57 ASA physical status I and II children aged 3 to 14 years, undergoing outpatient strabismus repair in two separate study centers. INTERVENTIONS: Patients were randomized to receive either 0.15 mg/kg intravenous (i.v.) ondansetron or 0.075 mg/kg i.v. droperidol shortly after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Number of episodes of emesis and times to discharge from the recovery room and ambulatory center were assessed. Twenty-nine (94%) of 31 children who received ondansetron and 21 (81%) of 26 children who received droperidol were emesis-free (p = NS). There were no significant differences in the number of episodes of emesis on the day after surgery or times to discharge. CONCLUSIONS: Ondansetron is at least as effective as droperidol in reducing the frequency of emesis in children after strabismus repair, and it did not shorten times to discharge home. The low number of patients in our study may have masked a difference in effect between the two groups. The clinician should decide whether the increased cost of ondansetron justifies its use over other antiemetics. PMID- 7772362 TI - A random trial comparing recovery after midazolam-alfentanil anesthesia with and without reversal with flumazenil, and standardized neurolept anesthesia for major gynecologic surgery. AB - STUDY OBJECTIVE: To compare the recovery characteristics of total intravenous anesthesia (TIVA) using midazolam-alfentanil, with or without reversal with flumazenil to a standardized neurolept anesthesia with nitrous oxide (N2O). DESIGN: Randomized, double-blinded clinical study. SETTING: University medical center. PATIENTS: 80 ASA physical status I and II women scheduled for major elective gynecologic surgery. INTERVENTIONS: Patients were anesthetized with one of three different anesthetic techniques. Patients in the TIVA group with reversal received midazolam-alfentanil reversed with flumazenil (Group 1), the TIVA group without reversal received midazolam-alfentanil reversed with placebo (Group 2), and patients in the neurolept group received anesthesia using thiopental sodium, droperidol, fentanyl, and N2O (Group 3). MEASUREMENTS AND MAIN RESULTS: Recovery was assessed by an observer blinded to the treatment allocation, using a Modified Steward Recovery Score and judgment of orientation and comprehension, collaboration and degree of sedation for the first 4 hours after extubation. Arterial blood gases were measured 30 minutes after extubation. A questionnaire regarding the degree of perioperative amnesia was presented to the patients 4 and 24 hours after surgery. The recovery scores were better in the TIVA group with reversal than in the other two groups from 0 to 30 minutes postoperatively. No difference between the groups could be found thereafter, although after 30 minutes some resedation occurred in the TIVA group with reversal. The median injected amount of flumazenil in Group 1 was 0.5 mg. Respiratory depression (breathing frequency below 10 breaths/min) was reversed with naloxone in one patient in the TIVA group with reversal, five patients in the TIVA group without reversal, and no patient in the neurolept group (p < 0.001). On blood gas analysis, there was no evidence of hypoxemia or carbon dioxide retention. No difference was seen between the groups regarding consumption of analgesics, degree of amnesia, or patient rating of the quality of anesthesia. One patient in Group 2, however, recorded awareness at skin incision when questioned 4 hours after the operation, but could not recall this 20 hours later. CONCLUSIONS: TIVA with midazolam and alfentanil can be used for major gynecologic surgery. Recovery in the neurolept group was equal to recovery in the TIVA group without reversal, and flumazenil improves the recovery after midazolam anesthesia. Overall, in comparison with the neurolept technique no major advantage could be demonstrated using TIVA with midazolam-alfentanil. PMID- 7772363 TI - Risk of high spinal anesthesia following failed epidural block for cesarean delivery. AB - Recent case reports suggest there may be an increased risk of abnormally high blockade ("high spinal") from subarachnoid anesthesia if it is performed immediately after epidural anesthesia. We describe two cases of high spinal anesthesia following failed epidural block in obstetric patients scheduled for cesarean delivery. Using a retrospective chart review, we estimate the incidence of high spinal anesthesia to be 11% in patients after prior failed epidural blockade versus fewer than 1% in patients undergoing spinal anesthesia alone. PMID- 7772364 TI - Phrenic nerve injury following scalenectomy in a patient with thoracic outlet obstruction. AB - We present a case in which a patient with normal pulmonary reserve experienced orthopnea and hypoxia secondary to unilateral diaphragmatic paralysis following right scalenectomy. This operation was performed in an attempt to relieve neurovascular compromise at the thoracic outlet. To our knowledge, this association has not been previously described in the literature. PMID- 7772365 TI - The cost of modern technology. AB - Continuous infusion of intravenous (i.v.) drugs is increasing in popularity, as technological advances in equipment (such as "smart" pumps) and pharmacologic improvements of drugs (such as ultra-short acting drugs) are introduced into clinical anesthesia practice. Such new technology, however, also introduces potential new complications. We report one such complication associated with the improper manufacturing of a proprietary i.v. tubing and cassette system. PMID- 7772366 TI - Carbon monoxide intoxication during pregnancy: a case presentation and pathophysiologic discussion, with emphasis on molecular mechanisms. AB - In carbon monoxide (CO) poisoning, the mortality and morbidity risk does not always correlate with the level of carboxyhemoglobin (COHb). Recent studies confirm that the mitochondrial cytochrome portion of the respiratory chain is susceptible to CO toxicity at concentrations traditionally considered nontoxic. These laboratory findings correlate with subtle neurologic symptoms detected by psychometric studies in individuals many days from the time of acute intoxication. Additionally, in the pregnant patient, a time lag for both uptake and elimination of CO between the mother and fetus has been demonstrated, with the fetus at risk for hypoxia even when the mother's blood level of CO is nontoxic. Hyperbaric oxygen (HBO) therapy in pregnant patients has not been shown to have adverse effects on the fetus. We present a case of CO intoxication in late pregnancy treated with HBO therapy without adverse consequences. PMID- 7772367 TI - Anesthesia in the presence of complete heart block. PMID- 7772368 TI - The post-anesthesia recovery score revisited. PMID- 7772369 TI - Nebulized bupivacaine attenuates the heart rate response following tracheal intubation. AB - STUDY OBJECTIVE: To determine whether nebulized bupivacaine attenuates the acute hemodynamic response to laryngoscopy and intubation. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Operating room at a university medical center. PATIENTS: 40 health ASA physical status I and II patients scheduled for minor surgical procedures. INTERVENTIONS: Patients were randomized to receive 4 ml of a nebulized solution of either saline (n = 20) or 0.75% bupivacaine (n = 20) 15 minutes before induction of anesthesia. On completion of the aerosol treatment, fentanyl 1.5 micrograms/kg was given intravenously (i.v.), and 3 minutes later anesthesia was induced with thiopental sodium 5 mg/kg i.v. and succinylcholine 1.5 mg/kg i.v.. Laryngoscopy was begun 60 seconds after induction, and the trachea was intubated at 90 seconds. Anesthesia was maintained with 50% nitrous oxide in oxygen following intubation, and 1% isoflurane was administered at 180 seconds. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR) and blood pressure were recorded automatically every 30 seconds for 5 minutes. Bupivacaine significantly attenuated HR (p < 0.05) but not the hypertensive response to laryngoscopy and intubation. CONCLUSION: Nebulized 0.75% bupivacaine was only partially effective in blunting the hemodynamic response to tracheal intubation. PMID- 7772370 TI - MR imaging of the retroperitoneum. AB - The diagnosis of retroperitoneal pathology has historically presented a challenge to physicians. The signs and symptoms of retroperitoneal diseases are myriad and often subtle. Cross-sectional imaging techniques have therefore had a major impact on retroperitoneal diagnosis. Computed tomography (CT) is currently the standard imaging technique for evaluating the retroperitoneum. Magnetic resonance (MR) imaging is also well suited for retroperitoneal imaging and has several advantages over CT. MR imaging is the preferred technique in patients with contraindications to iodinated contrast material due to renal dysfunction or allergy. It excels at evaluating the blood vessels, providing a reliable assessment of vessel patency, aneurysm, or dissection. The ability of MR imaging to acquire images without exposure to ionizing radiation facilitates imaging of obstetric and pediatric patients. The ability to acquire images in any plane is a distinct advantage for assessing the extent and origin of retroperitoneal pathology, although this can now be accomplished with spiral CT as well as MR imaging. The spatial resolution of CT is currently superior to MR imaging for most retroperitoneal studies, but this may change with continued technological advances such as improved phased array coil systems (Bidgood WD Jr, Schiebler ML. Retroperitoneum and mesentery. In: Ros PR, Bidgood WD Jr, eds. Abdominal magnetic resonance imaging. St. Louis: Mosby Year Book, 1993:310-47). Finally, MR imaging provides the flexibility to tailor each examination to the specific clinical question. With few exceptions, anything CT can do in the retroperitoneum, MR imaging can do as well or better. PMID- 7772371 TI - Echo planar imaging of the abdomen. AB - Echo planar imaging (EPI) is an ultrafast magnetic resonance (MR) imaging method first proposed more than 15 years ago. With EPI, all the information necessary to create an image is obtained very rapidly (typically on the order of 50-150 ms). Special hardware modifications are needed, particularly in the magnetic field gradients and data acquisition systems, to permit such high-speed imaging. In the abdomen, EPI images are insensitive to degradation from breathing or peristaltic motion. The essentially infinite repetition time and lack of motion-induced blurring can improve lesion characterization compared with standard imaging methods. Segmented EPI permits high-resolution T2-weighted images to be acquired within a single breath-hold. Diffusion imaging, which was previously restricted to the brain, can now be done in the abdomen because of the relative insensitivity of EPI images to bulk motion. Diffusion imaging of the kidney has been found to correlate with its functional status. By using EPI readouts, MR angiography can be done more quickly. Further work is needed to improve the spatial resolution and overcome magnetic susceptibility artifacts, particularly with single-shot EPI. Nonetheless, EPI offers considerable potential for improved anatomical and functional imaging of the abdomen. PMID- 7772372 TI - Magnetic resonance imaging of the liver. AB - A variety of diffuse and focal disease processes affect the liver. MRI is likely the imaging modality of choice for investigation of patients suspected of having diffuse disease such as cirrhosis, hemochromatosis, or fatty infiltration. MRI is extremely effective at detecting and characterizing focal hepatic lesions. In particular, patients suspected of possessing hemangiomas, hepatocellular carcinoma, or hypervascular liver metastases are better evaluated by MRI than other imaging modalities. Immediate post gadolinium spoiled gradient echo and T2 weighted fat suppressed spin echo are very effective at lesion detection, whereas serial post gadolinium spoiled gradient echo is essential for lesion characterization. New fast T2-weighted sequences and tissue specific contrast agents may further increase the role of liver MRI by shortening exam time and increasing sensitivity and specificity, respectively. PMID- 7772373 TI - Magnetic resonance imaging of the spleen and pancreas. AB - MRI of the spleen and pancreas requires specialized sequences which diminish artifacts in the upper abdomen. High temporal resolution sequences (e.g., spoiled gradient echo) acquired immediately after intravenous Gd-DTPA administration are necessary for imaging both the spleen and pancreas. In evaluating the spleen, early post Gd-DTPA images are essential as many focal disease processes (e.g., lymphomatous deposits or metastases) equilibrate rapidly (< 2 min) with splenic parenchyma. Complete pancreatic examination also requires the use of T1-weighted fat suppressed spin echo. T2-weighted images provide complementary information in a number of settings, in particular in the evaluation of islet cell tumors. Pancreatic ductal carcinoma is low signal on T1-weighted images and enhances in a diminished fashion on immediate post Gd-DTPA images. These tumors are well differentiated from focal chronic pancreatitis and islet celltumors based on their appearances on combined T1, T2-weighted and immediate post Gd-DTPA enhanced images. PMID- 7772374 TI - Magnetic resonance imaging of the adrenal gland and kidney. AB - MR is able to detect and characterize the majority of disease entities which affect the adrenal glands and kidneys. In the evaluation of the adrenal glands in phase and out-of-phase T1-weighted imaging may be the most effective noninvasive method to distinguish benign adenomas from malignant masses. T2-weighted images are sensitive and relatively specific for the investigation of pheochromocytoma. Although MRI is excellent at evaluating the kidneys, the lower cost and good image quality of CT render it the primary diagnostic tool for renal imaging. The major current applications for MRI of the kidneys include evaluation of patients with allergy to iodinated contrast, renal failure, and the characterization of complicated renal lesions. Evaluation of venous thrombus in the context of renal cancer is likely also a useful role for MRI. PMID- 7772375 TI - A practical method for fission yeast transformation by electroporation. AB - High-voltage shock within a very short duration under the proper conditions causes cells to incorporate exogenous macromolecules. This technique, electroporation, has been widely used in recent years to transform many organisms. We determined optimum conditions for fission yeast transformation using this method. Of nineteen combinations of electric field strength and pulse time examined, 1.75 kV/0.2 cm, 4 msec pulse was found to provide approximately 4.0 x 10(5) transformants per micrograms of DNA. Other factors responsible for the transformation efficiency in fission yeast are also discussed. PMID- 7772377 TI - New DNA data collected and processed at DNA Data Bank of Japan. PMID- 7772376 TI - Phenotypic and molecular characterization of croaker, a new mating behavior mutant of Drosophila melanogaster. AB - Mating of Drosophila melanogaster is a stereotypically patterned behavior consisting of a fixed sequence of actions that is primarily under genetic control. Although courtship can be easily monitored and quantified, little is known about its neural basis. To obtain a better understanding of cellular and molecular mechanisms underlying courtship, we have isolated mutants that disrupt specific aspects of mating behavior. The croaker mutant was isolated from approximately 1,000 lines harboring single P-element insertions by screening for aberrant courtship song: croaker males often generate polycyclic pulse song while most of the song pulses are monocyclic in the wild-type. The mutant is also defective in flight. Intracellular recordings of excitatory junction potentials from larval body wall muscles and Ca++ action potentials from adult indirect flight muscles demonstrated that neuromuscular transmission and Ca++ electrogenesis in the muscle fibers are not impaired by the croaker mutation. To define the croaker gene molecularly, genomic DNA surrounding the P-element insertion site was cloned by plasmid rescue and subsequent screening of a cosmid library. Northern blotting with the genomic DNA probes detected three transcripts in the wild-type, which were not expressed in the croaker mutant. PMID- 7772378 TI - Geographical distribution of the Hbb haplotypes in the Mus musculus subspecies in eastern Asia. AB - We surveyed the geographical distribution of Hbb haplotypes of the house mouse, Mus musculus, in the former USSR and the northern part of China. Mice with the w1 haplotype were distributed from the coastal area of the Black Sea to the Maritime Province of Siberia in the former USSR and in the area north of the Yangtze River in China. Mice with the p haplotype were found in the areas surrounding those populated with the w1 haplotype mice. In the Maritime Province and the southern part of Siberia, the d haplotype was predominant. The correlation between the geographical variation of the Hbb haplotypes and the distribution of the Mus musculus subspecies in the eastern part of the Eurasian Continent, is discussed. PMID- 7772379 TI - Deletion of the Wilson's disease gene in hereditary hepatitis LEC rats. AB - LEC rats develop disorder of cooper metabolism and hepatitis similar to those of human Wilson's disease. We recently demonstrated that the gene responsible for hepatitis (hts) of LEC rats is homologous to Wilson's disease gene (WD). The present study showed a deletion of at least 90 base pair of WD cDNA in LEC rats, which corresponds to nucleotides 3981 to 4071 in human WD cDNA sequence. This deletion was linked with hepatic copper accumulation and hepatitis, and considered to be a primary mutation for hepatic disorder in the LEC rat. The WD gene was assigned to rat chromosome 16 at band q12.2-q12.4 by fluorescence in situ hybridization (FISH). PMID- 7772380 TI - DNA sequence changes in mutations in the tonB gene on the chromosome of Escherichia coli K12: insertion elements dominate the spontaneous spectra. AB - To obtain insight into the nature and mechanisms of spontaneous mutations, Escherichia coli K12 strain TM31 was constructed to determine, by DNA sequencing, the mutational spectrum of the tonB gene on the chromosome. We inserted the chloramphenicol resistant gene 1.6 kb upstream of the tonB gene, thus making it possible to retrieve the mutated tonB gene from the chromosome by shotgun cloning using a drug-resistant marker. The spontaneous mutation frequency in the tonB gene, which was judged by its colicin B-resistant phenotype, is 3-10 x 10(-7). Spontaneous mutations were dominated by large insertions that are identified by DNA sequencing to be IS elements; IS1 dominated, but IS2, IS5, and IS10 were also obtained. In uvrA- strain, transposition of both IS10-R and IS10-L are equally increased, suggesting the interaction of the UvrA protein and IS10 transposition. The base substitutions are the second largest group of mutations, among which G:C ->A:T transition is predominant. Deletions also contribute significantly in wild type with regard to DNA repair and uvrA- strains, but not recA- strain, suggesting that the RecA protein is involved to some extent in deletion formation. Endpoints of these deletions do not always correlate with the presence of repeated sequences, indicating the absence of homologous recombination for deletion formation. PMID- 7772381 TI - Cytogenetical studies on the genus Oryza. XIV. Intergeneric hybridizations between tetraploid Oryza species and diploid Leersia species. AB - Intergeneric hybrids involving Oryza punctata (2n = 48, BBCC) with Leersia tisseranti (2n = 24), O. punctata with L. perrieri (2n = 24), O. latifolia (2n = 48, CCDD) with L. tisseranti and O. latifolia with L. perrieri were produced at frequencies varying from 0.11% to 0.23% of the pollinated spikelets. Plant morphologies of the hybrids strongly resembled the tetraploid Oryza species. Five hybrids obtained from the four cross-combinations had the expected chromosome number of 2n = 36 (trihaploid) in the somatic cells. The average meiotic chromosome pairings per cell were 0.23II + 35.58I + 0.14(1)/2I (dividing univalent) for O. punctata x L. tisseranti; 0.11II + 35.51I + 0.22(1)/2I for O. punctata x L. perrieri; 0.17II + 35.63I + 0.11(1)/2I for O. latifolia x L. tisseranti; and 0.25II + 35.49I + 0.15(1)/2I for O. latifolia x L. perrieri. From these results, it seems that most of the bivalents observed at MI with a low frequency had originated from the autosyndetic association of the chromosomes of O. punctata or O. latifolia. The results described above suggest that there is no genomic relationship between the parental species in each cross combination. PMID- 7772382 TI - Relationships between morphometric and mitochondrial DNA differentiation in laboratory strains of musk shrews (Suncus murinus). AB - Morphometric differentiation among six strains of musk shrews (Suncus murinus) originating in Bangladesh (BAN), Sri Lanka (SRI), and four Japanese areas, Nagasaki (NAG), Okinawa Island (OKI), Tokunoshima Island (TKU), and Taramajima Island (TR), was examined by use of skull and external measurements. These data were compared with mitochondrial DNA (mtDNA) differentiation previously reported. Significant sexual dimorphism was observed in all morphometric characters of the six strains, except for two characters in the TR strain. The six strains were clearly grouped by principal component analysis into three body-size types: large BAN shrews, intermediate SRI shrews, and small Japanese shrews. By canonical discriminant analysis, the NAG strain was further distinct from the other three Japanese strains despite their apparent similarities in external morphology, and was characterized by having the most unusual shape in the six strains. No individuals were misclassified as to their geographic origin for both sexes of the six strains. The morphometric differentiation pattern based on only the first canonical variate, extracting an overall size factor, was concordant with the mtDNA differentiation pattern (rss = 0.944, P < 0.001 in males and rss = 0.930, P < 0.001 in females). In contrast, the morphometric differentiation pattern estimated from the second to the fifth canonical variates, representing shape factors, was apparently discordant with the mtDNA differentiation pattern (rss = 0.467, P > 0.05 in both sexes). It was previously reported that a partial premating reproductive isolation mechanism is caused by the difference in body size between mating pairs. Thus, body size may be a factor useful for understanding the mechanisms of population differentiation in this species. PMID- 7772383 TI - Repetitive DNA sequence families in Hemitaxonus minomensis and H. athyrii (Hymenoptera; Tenthredinidae). AB - Families of the repetitive DNA sequences from Hemitaxonus minomensis and H. athyrii were characterized. pHMS family and pHME family in H. minomensis consist of tandemly arranged arrays whose basic repeat units are 260 bp and 330 bp, respectively. pHAE family in H. athyrii consists of a tandemly arranged array whose basic repeat unit is 330 bp. pHMS family and pHME family occupy approximately 4.8% and 0.07% of the genome of H. minomensis, respectively. By contrast, in H. athyrii, pHAE family comprise 0.04% of the genome. Nucleotide sequence comparison of these three repetitive families showed very little homology. Southern blot hybridization using six species of Hemitaxonus showed that these repetitive families are species specific. PMID- 7772384 TI - DNA fingerprinting of animal genomes by CA-repeat primed polymerase chain reaction. AB - CA-repeat primed polymerase chain reaction (CAP-PCR), using degenerate primers which anneal at the ends of (CA)n sequences in eukaryotic genomes, was attempted to assess its potential to monitor the genomic polymorphisms in various animals. Three mammalian, three avian, one fish and one insect species were examined and all showed primer-specific DNA fingerprints by CAP-PCR. Polymorphic bands observed in a laboratory-bred vole family were segregated in Mendelian manner. The present CAP-PCR DNA fingerprinting therefore is a simple and useful method for examining genomic variations in most animals without prerequisite knowledge of DNA sequences. PMID- 7772385 TI - Analysis of the tyrosinase gene of the Japanese pond frog, Rana nigromaculata: cloning and nucleotide sequence of the genomic DNA containing the tyrosinase gene and its flanking regions. AB - Three genomic DNA fragments containing the tyrosinase-encoding gene (TYR) of the Japanese pond frog, Rana nigromaculata, were cloned. The first, clone I, was isolated from a genomic library of sperm DNA using the mouse TYR cDNA as the probe and contained a DNA segment similar to exon 4 of the mouse TYR gene. Subsequently, the TYR cDNA was isolated by screening a frog embryo cDNA library using clone I as the probe. Two clones that contain genomic DNA of the TYR gene were isolated also from a blood cell DNA library using the frog TYR cDNA as the probe. Comparison of the nucleotide (nt) sequences of the genomic clone II DNA and the cDNA revealed that clone II contained a 3,140-bp DNA fragment consisting of the 5'-flanking region, the first exon, and a part of the first intron. The region upstream of the coding region contained the characteristic sequences for regulatory elements, including TATA- and CAAT-motifs, and also a pigment cell specific promoter element, which is shared by the promoter regions of the vertebrate TYR genes. A 764-bp segment containing an upstream 748-bp non-coding region and 16-bp coding region was functional for expression of the promoter-less cat gene on a plasmid in the transiently transformed albino frog melanophore. The genomic clone III contained the 3'-untranslated region of the mRNA and its 3' flanking region. Thus, the cDNA plus genomic DNA fragments isolated here cover the entire TYR gene and its flanking regions. PMID- 7772386 TI - Measuring outcome in counselling: a brief exploration of the issues. PMID- 7772387 TI - General practice fundholding: time for a cool appraisal. PMID- 7772388 TI - Care of patients with selected health problems in fundholding practices in Scotland in 1990 and 1992: needs, process and outcome. AB - BACKGROUND: At the time of the introduction of fundholding, a number of potential benefits and concerns about fundholding were debated. AIM: A study was undertaken to compare process and outcome of care in patients with different levels of physical, social and psychological need in 1990 and 1992 in six fundholding groups in Scotland. METHOD: Patients aged 16 years and over consulting with a range of marker conditions in 1990 and 1992 completed a pre-consultation health status questionnaire asking about physical, social and psychological problems, and a postconsultation satisfaction/enablement questionnaire asking about their ability to cope, and understand their illness. Main outcome measures were consultation length and satisfaction/enablement score. RESULTS: Of patients attending in the study period, 39% consulted for one or more marker condition. The proportion of patients reporting social problems rose between 1990 and 1992 for 11 out of 12 conditions. Overall, consultation lengths remained constant. Patients wanting to discuss social problems had significantly longer consultations than those reporting no social problems or problems they did not wish to discuss. The proportion of patients expressing enablement dropped for eight conditions and rose for four between 1990 and 1992. The decrease in the proportion expressing enablement remained after controlling for the rise in the percentage reporting social problems. Patients who had social problems they did not wish to discuss but a general health questionnaire score of five or more were the group reporting lowest enablement. Significantly more patients with pain, skin problems and digestive problems reported social problems and significantly fewer of them reported enablement in 1992 compared with 1990. Patients with diabetes, angina, chronic bronchitis and problems seeing fared relatively well over the study period. Some patients with psychosocial problems fared poorly (they had relatively short consultations and were unlikely to express an ability to cope/understand their illness). CONCLUSION: The issue of whether benefits to some patient groups from recent health service changes may be matched by disadvantage to other groups, for example those with clinical problems with no financial incentive to provide pro-active care or with psychosocial difficulties, is discussed. PMID- 7772389 TI - From the surgery to the surgeon: does deprivation influence consultation and operation rates? AB - BACKGROUND: Concern about equity of access to health care has increased since the health care reforms implemented in the 1990s. Access to specialist health care is controlled by general practitioners; assessing and ensuring equity should therefore begin in general practice. AIM: This study set out to determine whether there are socioeconomic differences in the relationship between expressed need for possible surgical intervention (consulting a general practitioner) and surgical provision. METHOD: Information on the social class distribution of expressed need was obtained from the third national morbidity survey (1981-82) for 140,049 patients consulting a general practitioner. The conditions examined were: inguinal hernia, gallstones, tonsillitis, varicose veins, cataract and osteoarthritis. This expressed need was compared with the appropriate operation for all residents of North East Thames Regional Health Authority from January 1991 to July 1992 classified, according to area of residence, by the Townsend deprivation score. RESULTS: The relationship between expressed need and provision by deprivation was concordant for some conditions, but discordant for others. For cataract and tonsillitis, there was an inverse U pattern between increasing deprivation and both patient consultation and operation ratios. For varicose veins, deprivation was associated with higher patient consultation and operation ratios. For hernia, gallstones and osteoarthritis, consultations increased with deprivation, but operation ratios were either unrelated to deprivation scores (hernia and gallstones) or decreased by deprivation score (hip operations). CONCLUSION: There are marked socioeconomic differences in consultation ratios for these common conditions which may not be matched by operation ratios. For discordant comparisons, people in the most deprived quartiles were generally least likely to receive surgery despite being most likely to consult a general practitioner with symptoms. If validated, these findings have important implications for general practice and service providers. PMID- 7772390 TI - Patients who do not receive continuity of care from their general practitioner- are they a vulnerable group? AB - BACKGROUND: Continuity of care is much valued by general practitioners but little is known about those patients who do not receive continuity of care. AIM: This study set out to identify and describe a group of patients who did not receive continuity of care from the general practitioner with whom they were personally registered. METHOD: A total of 110 patients (71 female and 39 male) were identified, who did not receive continuity of care, defined as four consecutive face to face consultations which did not take place with the doctor with whom they were registered. This group was compared with an age and sex matched control group who did receive continuity of care, using general practice records, for demographic characteristics, morbidity, relationship problems, number of 'difficult' consultations, failure to attend appointments, and use of an accident and emergency department and of open access clinics. RESULTS: Patients in the study group were more likely to be under the age of 65 years than all patients on the doctor's list. Study patients were more likely than control patients to be in social class 4 or 5 living in a council house. Patients in the study group were more likely than controls to be depressed. Women patients in the study group were more likely to suffer from vaginal discharge. Men patients in the study group were more likely to complain of non-cardiac chest pain. The study group had more marital problems, parent-child relationship problems, and problems involving violence in the family, as well as other relationship problems. Relationship problems included the relationship with the doctor, since a third of all the consultations in the study group were recorded as 'difficult', compared with 3% in the control group. The study group patients were more likely than controls not to attend appointments which they had made, to use the accident and emergency department repeatedly, and to have used other open access clinics. CONCLUSION: Lack of continuity of care is associated with some additional morbidity, an increased number of relationship problems, 'difficult' consultations, and non attendances, and an increase in the use of open access clinics. The characteristics of this group of patients represent a syndrome which merits further study. PMID- 7772391 TI - Use of videotaped consultations in summative assessment of trainees in general practice. AB - BACKGROUND: There are many different methods by which trainees may be assessed summatively. AIM: The objective of the study was to determine if videotaped consultations could be used to identify reliably those general practitioner trainees who have not yet reached acceptable levels of competence. METHOD: Videotapes of 10 trainees carrying out normal consultations were assessed by 20 assessors for acceptable competence using a rating scale specifically developed for the purpose. RESULTS: A principal components analysis showed a strong correlation among the items in the rating scale used, indicating that a single underlying factor accounted for 76% of the overall scores. Agreement between assessors on the scoring of individual consultations was limited. There was much greater consistency with regard to the decision on overall competence, examined for the first consultation. A non-competent trainee would have a 95% probability of being identified by the process as described using two assessors for each videotape. The assessors had reached firm judgements on each trainee by the time four consultations had been viewed. CONCLUSION: The workload involved in producing and analysing the tapes is discussed. Considerations of patient consent are addressed. It is concluded that the use of videotaped consultations appears to offer a feasible and reliable method of summative assessment of general practitioner trainees. PMID- 7772392 TI - Somatic presentation of psychiatric morbidity in general practice. AB - BACKGROUND: Twenty per cent of new illnesses in general practice, and 3% of consecutive attenders, are incident cases of 'pure' somatization. AIM: This study set out to estimate the prevalence of consultations by patients with psychiatric morbidity who present only somatic symptoms (somatic presentation), and to compare this with the likely prevalence of pure somatization. METHOD: A cross sectional survey of consecutive general practice attenders was carried out. Psychiatric morbidity was measured using the general health questionnaire. Pure somatization was defined as medical consultation for somatic symptoms that were judged by a psychiatrist during an interview to be aetiologically attributable to an underlying psychiatric disorder but which were not recognized as such by the patient. RESULTS: Of attenders 25% were identified as somatic presenters. Of the somatic presenters interviewed one in six were estimated to be pure somatizers, which would extrapolate to 4% of attenders. Though all somatic presenters were probable cases of psychiatric disorder, subjects in this group had lower scores on the general health questionnaire than those who presented with psychological symptoms. General practitioner recognition of psychiatric morbidity was significantly lower among somatic presenters than for other subjects with psychiatric morbidity. CONCLUSION: General practitioner recognition of psychiatric morbidity could be improved for all types of somatic presentation, regardless of the aetiology of patients' somatic symptoms. There is a danger that concentrating attention on pure somatization may mean that psychiatric morbidity in the more common undifferentiated form of somatic presentation will be overlooked. PMID- 7772393 TI - Effect of structured postgraduate medical education on the care of patients with diabetes. AB - BACKGROUND: Diabetes can be effectively treated and monitored in general practice. Postgraduate medical education at a local level is required to support this strategic shift of medical care from hospital to general practice. AIM: This study set out to determine whether a structured educational programme initiated by and led by general practitioners, but involving all health professionals, leads to improved care for diabetic patients. METHOD: The primary health care teams from 12 of the general practices in Tynedale, Northumberland who attend the local postgraduate centre and refer patients to the local general hospital were involved in the educational initiative which led to a locally agreed protocol for diabetic care. A comparison was made of data for all diabetic patients, registered with the general practitioners in 1991, in the years 1986 and 1991 (before and after the educational initiative) in order to determine the prevalence of diabetes, place of care and treatment received, and to collect clinical information. RESULTS: More patients received general practice care only or shared care in 1991 than in 1986. There was a reduction in the use of oral hypoglycaemic agents among non-insulin dependent diabetic patients and more patients were maintained on diet alone. A greater proportion of patients were referred to dietitians, ophthalmologists and chiropodists in 1991 than 1986, and there was increased recording of, examination of, and identification of, diabetic complications. Little change was found in the mean values for clinical parameters between the two years. CONCLUSION: Structured educational programmes involving all professionals are an effective way of producing protocols that are adhered to by all concerned, and lead to improved clinical care for diabetic patients. PMID- 7772395 TI - Promoting exercise in primary care. PMID- 7772394 TI - Use of warfarin in non-rheumatic atrial fibrillation: a commentary from general practice. AB - Seven randomized trials published in the last six years have shown that warfarin reduces the risk of ischaemic strokes and death in patients with atrial fibrillation. The annual rates of major bleeding episodes in all these trials were low and, as a result, doctors in primary and secondary care are being encouraged to consider using warfarin for patients with atrial fibrillation unless there are obvious contraindications. However, the populations used in these studies were highly selected and rigorously monitored throughout the trial period to minimize the risk of bleeding in a way which probably could not be expected in routine primary care. Although the rates of major bleeding episodes were uniformly low, the rates of minor bleeding episodes were much higher and these could impact substantially on patients' views of the treatment and on the workload of the primary care team. Evidence is now at hand which allows the stratification of risk in patients with atrial fibrillation which should enable those who are at greatest risk to be considered for this form of treatment. Patients may develop risk factors over time which could render them unsuitable for continuation of warfarin therapy. The general practitioner is centrally placed to make the decision about initiating or continuing treatment or indeed stopping it. Several models for decision making in warfarin treatment from primary and secondary care are proposed. PMID- 7772396 TI - Teenage health. PMID- 7772397 TI - Stinging nettles for osteoarthritis pain of the hip. PMID- 7772399 TI - [Traumatic brain injury & mild hypothermia]. PMID- 7772398 TI - [A review on adjuvant analgesics for chronic pain with emphasis on neurogenic pain]. PMID- 7772400 TI - [Surgical outcome of cervical flexion myelopathy in young adults]. AB - We encountered five young male patients with cervical flexion myelopathy, and treated them all surgically. Symptoms were first noted at 15 to 18 years of age (mean: 16.6 years), and their ages at the time of admission to our hospital, ranged from 19 to 25 years old (mean: 20.8 years). Anterior decompression and fusion of the cervical spine with long bone graft following resection of two vertebrae was performed in three cases. The other two patients were treated by posterior fusion of five laminas (C3-C7) using Rogers' method. In selecting the surgical approach, we favored anterior fusion because it allows removal of anterior structures (vertebral bodies, intervertebral discs or osteophytes) compressing the cervical spinal cord in flexed neck position. Posterior fusion was performed in patients whose anterior structures compressing the cervical spinal cord extended over a wide area. Postoperative improvement of muscle weakness was observed in four patients, and sensory disturbance was alleviated in the remaining patient. However, the abnormal deep tendon reflexes and muscle atrophy in the upper extremities observed in all of the patients preoperatively improved in only two of them. Thus, all of the patients showed some neurological improvement, and surgical fusion of the cervical spine appeared to be an effective means of treating cervical flexion myelopathy in young adults. Both the anterior and the posterior approach were useful in treating cervical flexion myelopathy, but it was impossible to conclude which approach is more effective based on this small number of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772401 TI - [Detection of subclinical sensory nerve dysfunction in amyotrophic lateral sclerosis--a microneurographic study]. AB - In amyotrophic lateral sclerosis (ALS) sensory function has been considered to be normal on a clinical basis. There are, however, several pathologic reports indicating that peripheral sensory fibers are involved in ALS. To evaluate changes in sensory nerve function quantitatively, we measured compound nerve action potentials (CNAP) of the median nerve by means of intraneural microneurography (MNG) and compared the results between 16 patients with ALS, age matched 13 patients with Parkinson disease (PD) and 13 healthy controls. A tungsten microelectrode with a tip diameter of 1 micron was inserted percutaneously into the median nerve trunk at the elbow. With supramaximal electric stimulation on the median nerve at the wrist, the largest CNAP was recorded. The configuration of the CNAP was similar among three groups, consisting of a large triphasic wave followed by small multiphaic waves. In ALS patients the peak to peak amplitude (Amp) of the triphasic wave was 189.0 +/- 49.8 microV (mean +/- SD), which was significantly smaller than 273.1 +/- 90.0 microV in PD patients and 325.4 +/- 81.0 microV in normal controls (p < 0.01). The maximal nerve conduction velocity (NCV) in ALS was also reduced when compared with that in PD patients and in normal controls (p < 0.05). The average reduction in Amp in ALS was 58% of that in normal controls, while decrease in NCV was less apparent than Amp and 96% of normal controls. The Amplitude of nerve action potentials is considered to represent the density of large myelinated fibers more than 7 microns around the microelectrode.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772402 TI - [Role of nitric oxide produced by activated macrophages in their cytocidal activity against glial tumor cells]. AB - This study investigated the role of activated macrophages (M phi) in nitric oxide (NO) production and the tumoricidal effect of NO on glioma cells. Induced peritoneal M phi were prepared 6 days following the injection of thioglycollate broth into C3H/He N (H-2 kappa) mice. M phi were activated in vitro recombinant human interferon-gamma (IFN gamma) and lipopolysaccharide (LPS) into the culture medium of the elicited M phi. Two kinds of murine malignant glioma cell lines, RSV-M glioma (H-2 kappa) and VM-glioma (H-2b) were used as targets. P815 mastocytoma cells (H-2d) were used as a control target, since they are insensitive to tumor necrosis factor-alpha, but susceptible to NO derived from M phi. L-arginine-depleted medium was used to inhibit NO-mediated cytocidal activity against tumor cells. Cytotoxicity was assayed at various effector-to target ratios using an admixture of M phi and 1.5 x 10(4) 125I-labeled target cells 48 hours following co-culture. NO was measured in culture medium using Griess reagent, and the concentration of NO was expressed as mu mol/ml NaNO2. Peritoneal M phi induced only 10% and 15% lysis of RSV-M glioma and VM glioma cells, respective, and LPS augmented this killing activity of M phi to a maximum of 1.2 to 1.4 fold in a dose-dependent manner with dosages from 1 to 50 ng/ml. LPS demonstrated a synergistic action on M phi-mediated cytotoxicity 4 hours following pretreatment with IFN gamma. Alternatively, low doses of IFN gamma alone had no enhancing effect on M phi tumoricidal activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772403 TI - [The practical benefits of magnetoencephalography in comparison with electroencephalography in a patient with epilepsia partialis continua]. AB - A concurrent recording of electroencephalography (EEG), magnetoencephalography (MEG) and electromyography (EMG) was carried out in a patient with epilepsia partialis continua. He had continuous clonic jerks in his right hand and fingers. The EMG electrodes were placed on the thumb of his right hand. We observed numerous MEG spikes in the left central region and about half of them were accompanied by EMG potentials with a latency of about 20 msec. The EEG spikes appeared less frequently, had low amplitudes, and had unclear morphologies and further, no clear association with EMG potentials. MEG spikes were more reliably associated with individual jerks, exemplified by EMG potentials, than the EEG spikes. The MEG spikes were sharper than EEG spikes and were about 20 msec wide. The intracranial dipole localization of the MEG spikes was estimated by overlaying the calculated generator sites on magnetic resonance images. It was found that the spikes converged along a line, presumably the central sulcus. The practical benefits of the MEG as a diagnostic tool in epilepsy are illustrated. PMID- 7772404 TI - [Transcranial magnetic stimulation of the accesory nerve--investigation of the site and mechanism of excitation in the cat]. AB - The site where transcranial magnetic stimulation excites the accessory nerve was studied in 5 cats. Transcranial magnetic stimulation of the accessory nerve was recorded from the right trapezius. The accessory nerve was stimulated electrically at the C1 level, jugular tubercle and jugular foramen. The latencies of the compound muscle action potentials (CMAPs) for each portion were measured and compared with the magnetic response, which was coincidental with that of the jugular tubercle. The accessory nerve was then transected in steps distally from the C1 level, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared following the nerve transection at the jugular tubercle. The results of both approaches in this study conclude that transcranial magnetic stimulation excites the accessory nerve at jugular tubercle. This stimulation site was anatomically coincidental with that of the facial nerve and trigeminal nerve in being right before the point where the nerve bends. Following the accessory nerve transection at the C1 level, the amputation stump was moved cranially, and CMAPs disappeared. CMAPs recorded after the accessory nerve was returned to its original position. These examinations suggested that sudden alteration of the traveling lie of the nerve participates in the mechanism of transcranial magnetic stimulation. PMID- 7772405 TI - [Improvement of highly reproducible technique of four-vessel occlusion model and its study on metabolic changes of cerebral reperfusion in rats]. AB - The four-vessel occlusion method introduced by Pulsinelli et al is widely used as an experimental model for reversible forebrain ischemia in rats. However, this model has a major problem in the difficulty assuring complete occlusion of the vertebral arteries by electrocauterization through the alar foramina of the first cervical vertebra. Anatomical basis of the vertebral artery suggested by Sugio et al indicates that the vertebral artery at the level of the second cervical vertebral is visible. In this study, we further developed highly reproducible model of reversible forebrain ischemia, which is modified four-vessel occlusion in rats. Male Wistar rats were subjected to four-vessel occlusion. Under microscope the visible vertebral arteries at the second vertebra could be easily electrocauterized and completely cut by microscissors to yield complete cessation of circulation of bilateral vertebral arteries without failure. After 24 hours, animals were subjected to 15, 30 and 45 minutes of forebrain ischemia by occluding both common carotid arteries with Sugita's temporary clips. 31P magnetic resonance spectroscopy (31P-MRS) were obtained with a 6.3-T spectrometer to investigate sequential change of the in vivo brain energy metabolism. Our studies indicated that high energy phosphorus compounds were reduced in a few minutes after the induction of the forebrain ischemia, and they returned to the normal level after the recirculation. In addition, we monitored electroencephalogram (EEG) during the whole experimental period. The EEG showed a flat pattern after the induction of ischemia, and EEG recovered normal pattern within 12 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772406 TI - [A left-handed patient with disturbance of manipulating objects]. AB - We reported a left-handed patient with the disturbance of manipulating objects and the object pantomime. The patient was a 72-year-old man, admitted to Osaka Medical College Hospital complaint of the difficulty of object manipulation. The patient was alert, well oriented and attentive. On neurological examination the patient revealed grasp reflex in his left hand. On neuropsychological examination the patient spoke fluently, but his verbal comprehension was slightly disturbed. He could name popular objects only 9 out of 20 objects. On praxis examination he could pantomime the socially accustomed movements by command visually pantomime. He did not reveal buccofacial apraxia and constructional apraxia. However, the patient could not manipulate both single and pleural objects actually and pantomime without objects. On MRI the lesion was found in both frontal lobe, right medial frontal lobe and right temporal lobe. SPECT findings demonstrated that the bilateral parietal lobes were preserved and we speculated that the right supplementary motor area was assumed to be a crucial lesion for manipulating objects in the patient. PMID- 7772407 TI - [Positron emission tomographic findings of subependymal giant cell astrocytoma developed in tuberous sclerosis--a case report]. AB - Tuberous sclerosis (TS) is well known to be occasionally associated with subependymal giant cell astrocytoma (SGCA). SGCA is considered to be a benign tumor in its clinical course and morphology. However, this tumor is grown sometimes so rapid and caused hydrocephalus. To our knowledge, little is known about hemocirculation and metabolism, particularly in relation with proliferating activity of TS and SGCA. We measured hemocirculation and metabolism of SGCA developed in a case of TS using positron emission tomography (PET). A 13-year-old boy who had frequently developed convulsions four months after birth. He was diagnosed as TS and had been medically treated with anticonvulsants, since multiple intraventricular calcifications were detected by CT, at the age of five months. The convulsions had been well controlled. In March 1993, he presented with syncopal attack and admitted to our hospital. CT showed multiple subependymal nodules. Among the nodules, one of the left anterior horn exceeded 2cm in size obliterated Monro's foramen. The tumor was homogeneously enhanced with contrast medium. The lesion detected by postcontrast T1-weighted MR imaging had almost the same status as that by CT. T2-weighted image revealed cortical tubers as high intensity area at the left frontal and parietooccipital regions. PET was performed with the Headtome IV. Hemocirculation of the tumor was lower than that of contralateral gray matter, which suggested poor blood supply. The oxygen and glucose metabolism of the tumor were decreased compared with contralateral gray matter, indicative of a low activity of proliferation and a clinically benign tumor in the present case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772408 TI - [A case of malignant rheumatoid arthritis with lupus anticoagulant and cerebral infarction]. AB - We reported a case of malignant rheumatoid arthritis (MRA) with cerebral infarction associated with a possible cause of lupus anticoagulant. The patient was a 68-year-old woman who had received treatment for rheumatoid arthritis (RA) from 15 to 16 years ago. She consulted to our hospital with a major complaint of right hemiplegia. Brain CT revealed a low density area in the left hemisphere. She was diagnosed as cerebral infarction and hospitalized. Since she was noted to have hypocomplementemia, interstitial pneumonia and pericarditis, she was diagnosed as MRA. Coagulation test disclosed positive lupus anticoagulant (LA). Generally, CNS disorders in MRA are uncommon. Cerebral infarction was complicated in the present case, suggesting the involvement of antiphospholipid antibodies as its pathogenesis. PMID- 7772409 TI - [Cerebellar ataxia, 2) dementia, 3) syncopal attack, 4) character change]. PMID- 7772410 TI - [A 65-year-old woman with dysarthria, dysphagia, weakness, and gait disturbance]. AB - We report a 65-year-old woman with progressive dysarthria, dysphagia, weakness, and gait disturbance. The patient was well until 59 years of age (January of 1986) when she noted bilateral ptosis. One year later, she noted a gradual onset of difficulty in speech (articulation). Her speech slowly deteriorated and she noted weakness in chewing power and difficulty in swallowing in addition. In October 1987, she developed emotional incontinence. In January of 1988, she started to drag her left foot. She was admitted to our hospital on June 13 of 1988. On admission, she was alert and general physical examination was unremarkable. Neurologic examination revealed no dementia; her higher cerebral functions appeared intact. Ptosis was present bilaterally more on the right. She showed difficulty in opening her eyes on command; no contraction of the frontal muscles was seen upon attempted eye opening. There was a moderate limitation in the vertical gaze. Forced laughing and crying were seen. Facial muscles were moderately weak without apparent atrophy. The movement of the soft palate was very weak, and swallowing disturbance was more prominent for liquid staff. The tongue appeared somewhat small, however, no fasciculation was noted. Her step was small and the posture was stooped. Retropulsion was present, however, Romberg's sign was absent. No muscle atrophy was apparent, however, diffuse mile to moderate muscle weakness was noted in all four limbs. Cerebellar sign was absent. Deep tendon reflexes were exaggerated bilaterally, and Babinski sign was present on the left side. Sensation was intact. Routine blood tests were unremarkable as was a cranial CT scan. Her ptosis did not improve after 10 mg of edrophonium injection. CSF was also normal. She was transferred to another hospital but her neurological disabilities further progressed. In 1989, she was totally unable to move her limbs; she could only move her eyes; still consciousness was clear without dementia. She developed respiratory difficulty and expired on July 25, 1992. She was discussed in a neurological CPC, and the opinions were divided into ALS and primary lateral sclerosis (PLS). The chief discussant arrived at the conclusion that the patient might have had the pyramidal form of ALS. Postmorten examination revealed marked myelin pallor in the anterior as well as lateral corticospinal tracts. Pyramidal tract degeneration was prominent starting at the level of the cerebral peduncle and was continued to be seen until the level of lumbar cord. The number of anterior horn cells showed only slight decrease in the cervical level, however, it was normal in the lumbar cord.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772411 TI - Facile desulfurization of cyclic thioureas by hydrogen peroxide in acetic acid. AB - A simple, mild and synthetically useful method for the desulfurization of cyclic thioureas and related compounds, existing as thiol-thione tautomeric mixtures, by hydrogen peroxide in acetic acid is proposed. The effect of substituting different solvents for the acetic acid was investigated. PMID- 7772412 TI - An alternative synthesis of the NMDA antagonist CGS 19755 via free radical carbamoylation of ethyl isonicotinate. AB - The NMDA antagonist CGS 19755 (cis-4-phosphonomethyl-2-piperidinecarboxylic acid) has been prepared by applying Minisci reaction conditions [formamide, hydrogen peroxide, iron(II) sulfate] to ethyl isonicotinate, reduction of the ester with sodium borohydride, alcoholysis of the 2-carboxamide, formation of 4 (diethylphosphonomethyl)-2-pyridinecarboxylate, hydrogenation of the pyridine nucleus, and acid hydrolysis. The overall, unoptimized yield was around 11%. The procedure employs cheap starting materials, is practical and avoids the use of toxic and hazardous cyanotrimethylsilane which is used in the published procedure. PMID- 7772413 TI - Incrustoporin, a new antibiotic from Incrustoporia carneola (Bres.) Ryv. (Basidiomycetes). PMID- 7772414 TI - Does the synthesis of ribosomal RNA take place within nucleolar fibrillar centers or dense fibrillar components? A critical appraisal. AB - The localization of transcribing rRNA genes within nucleoli of mammalian cells, although intensively studied, has not been established. Most published papers on this topic situate transcribing ribosomal genes either to nucleolar fibrillar centers or to nucleolar dense fibrillar components. To clarify this point, we have generated the electron microscopic affinity cytochemistry picture of the nucleolus of cultured mammalian cells. Three kinds of affinity probes have been used: (1) probes to nucleolar chromatin, including rDNA sequences; (2) probes to a number of macromolecules (such as RNA polymerase I) which are directly, or indirectly, involved in the synthesis and processing of rRNA and formation of preribosomes; (3) antibodies to bromouridine for a recently standardized nonisotopical method depicting incorporated bromouridine within RNA. The results suggest the localization of transcription sites not only to dense fibrillar components but also to the border region between these components and fibrillar centers. Our data support a hypothesis that in metabolically active mammalian nucleoli, fibrillar centers and dense fibrillar components form a single functional domain for the transcription of rRNA genes, with nascent transcripts generating "automatically" dense fibrillar components. Through the active process of transcription, individual rRNA genes thus become engulfed within dense fibrillar components. PMID- 7772415 TI - FTIR spectroscopy of alanine-based peptides: assignment of the amide I' modes for random coil and helix. AB - Fourier transform infrared (FTIR) spectroscopy has been used to explore the thermal unfolding of three helical, alanine-based peptides. Each of the peptides follows the general sequence Ac-(AAAX)nA-NH2 where X is either Lys+ or Arg+ and n = 3 or 4. These particular peptides were chosen because they contain varying amounts of 3(10)- and alpha-helix. The amide I' bands for all three peptides, under helix forming conditions, are between 1632 and 1635 cm-1. These results are incongruous with the assignment for alpha-helices in proteins where amide I' bands are usually found above 1650 cm-1. At elevated temperatures, all the peptides exhibit amide I' bands of 1642 cm-1, which is the accepted value for random coil. Variable temperature spectra for the 4K peptide (n = 4, X = Lys+), which is the most alpha-helical of the three peptides at 1 degree C, reveal an isosbestic point suggesting a cooperative two-state unfolding transition. The other peptides, however, did not reveal an isosbestic point, thereby indicating the presence of an intermediate, perhaps 3(10)-helix, along the thermal unfolding pathway. PMID- 7772416 TI - Structure of Lumbricus terrestris hemoglobin at 30 A resolution determined using angular reconstitution. AB - The three-dimensional (3D) structure of the giant hemoglobin of the common earthworm Lumbricus terrestris was determined from cryomicroscopical images of a vitrified molecular solution. From about 5000 molecular images, the best-fit 3D structure was calculated using recently developed analysis techniques. Multivariate statistical analysis data compression and automatic classification were used to find the characteristic projection images of the oligomer. The angular reconstitution approach was then applied to find the Euler angle orientations of these characteristic views. The Lumbricus hemoglobin molecule has an overall D6 (622) point-group symmetry and is found to have a local threefold symmetry axis within the 1/12th subunit. This additional symmetry appears to predict the presence of 36 abcd globin tetramers in the Lumbricus hemoglobin or a total of 144 heme chains for the whole oligomer. A distinct doughnut-shaped structure is elucidated in the center of the molecule. This central subunit, representing around 10% of the protein volume, may consist of non-heme-containing linker chains found generally in giant annelid hemoglobins. PMID- 7772417 TI - Molecular design of the voltage-dependent, anion-selective channel in the mitochondrial outer membrane. AB - The mitochondrial outer membrane contains numerous copies of a channel protein, VDAC, that is thought to be the main permeability pathway through this membrane for polar molecules and ions. Low-dose electron microscopy has been used to obtain images of two-dimensional crystals of this channel (produced by treating outer membranes from fungal mitochondria with phospholipase A2) embedded in vitreous ice or aurothioglucose. The angular orientation of the channels in the unit cell of one type of array has been determined by rotational correlation analysis. The location of the amino-terminal segment of the protein (which, according to circular dichroism, forms an alpha-helix in nonpolar solvents and detergent solutions) has been determined by labeling arrays with Fab prepared from antibodies directed against residues 1-20. The three-dimensional structure of the channel has been obtained by applying Fourier reconstruction methods to projections of tilted crystals embedded in aurothioglucose, followed by averaging of the three non-symmetry-related channels in the unit cell. The results of this study indicate that the wall of VDAC's lumen has several irregular features (uneven height, grooves) and that the aminoterminal segment extends away from the lumen in this crystalline state. PMID- 7772418 TI - A novel method for transfer of two-dimensional crystals from the air/water interface to specimen grids. EM sample preparation/lipid-layer crystallization. AB - Transfer of two-dimensional (2-D) crystals formed on lipid layers by suspension from a wire loop is described. This method gives better recovery and better preservation of 2-D crystals than attained in the past. The method has been applied to crystals of yeast RNA polymerase II to enable their analysis in the frozen hydrated state. PMID- 7772419 TI - Muscarinic receptor subtypes: do they have a place in clinical anaesthesia? PMID- 7772420 TI - Metabolic control of non-insulin-dependent diabetic patients undergoing cataract surgery: comparison of local and general anaesthesia. AB - We studied 40 elderly patients undergoing cataract surgery. Ten non-insulin dependent diabetes mellitus (NIDDM) patients received standardized general anaesthesia, 10 NIDDM patients received local anaesthesia using retrobulbar block, 10 non-diabetic control patients received general anaesthesia and 10 non diabetic controls received retrobulbar block. We measured sequential changes in blood glucose, lactate and beta-hydroxybutyrate, serum cortisol and insulin, and plasma non-esterified fatty acid concentrations until 4 h after operation. The results showed that in both general anaesthesia groups, NIDDM and control, blood glucose and serum cortisol concentrations increased significantly during surgery, before returning to normal by 4 h after operation; in both local anaesthesia groups, glucose and cortisol concentrations changed little during surgery. Serum insulin concentrations increased 30 min after operation to coincide with the peak of the glucose increase in the non-diabetic patients who received general anaesthesia, but no insulin response was seen in the diabetic general anaesthesia patients. Blood glucose and insulin concentrations increased in patients who received local anaesthesia (NIDDM and controls) when they ate after operation. The results show that cataract surgery under local anaesthesia provides improved metabolic control for the diabetic patient. Its use maintains glucose homeostasis, prevents the increases in cortisol and glucose which are seen under general anaesthesia and obviates the need for postoperative starvation. PMID- 7772421 TI - Infraorbital nerve block in neonates for cleft lip repair: anatomical study and clinical application. AB - Infraorbital nerve block in neonates is not well described although it has been suggested that bilateral infraorbital nerve block is the local analgesic technique of choice for early repair of cleft lip. The purpose of this study was to determine the location of the infraorbital nerve in neonatal cadavers and to identify clinically useful landmarks. Thirty infraorbital nerves were identified in 15 neonatal cadavers with a mean weight of 2.85 (SD 0.32) kg (range 2.45-3.5 kg) via an upper buccal sulcus incision. The mean distance from the infraorbital nerve to the base of the alae nasi was 7.7 (SD 1.3) mm on the left and 7.5 (0.8) mm on the right. A line drawn from the angle of the mouth to the midpoint of the palpebral fissure measured 30.6 (1.9) mm (left) and 30.7 (1.8) mm (right). The nerve was situated approximately halfway along this line at a point 15.5 (1.5) mm (left) and 15.2 (1.4) mm (right) from the angle of the mouth. These measurements were used to perform bilateral infraorbital nerve blocks in four neonates undergoing cleft lip surgery under general anaesthesia, thereby providing analgesia with minimal risk of respiratory depression. PMID- 7772422 TI - Low-dose droperidol reduces postoperative vomiting in paediatric day surgery. AB - In a prospective, randomized, blind study, we assessed the effectiveness of droperidol 20 micrograms kg-1 i.v., given at induction of anaesthesia, in preventing postoperative vomiting in paediatric day-case patients. We studied 270 children, aged 1-15 yr, undergoing body surface surgery. There was a significant reduction in the incidence of vomiting in the recovery room (1.4% vs 9.2%, P < 0.005) and in the day ward (9.4% vs 18.3%, P < 0.05) in patients receiving droperidol. There was no significant difference on the journey home (9.5% vs 17.83%, ns) or at home (16.7% vs 10.3%, ns). There was also a reduction in the severity of vomiting in the droperidol group. There were no adverse side effects. PMID- 7772423 TI - Extradural anaesthesia for caesarean section: a double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine. AB - Seventy-three parturients for elective Caesarean section were allocated randomly to receive extradural block with 20 ml of either 0.5% ropivacaine or 0.5% bupivacaine. If the block did not reach T6 within 30 min, another 5 ml of solution was given. If needed, a further 5 ml was given 45 min after the main dose. The mean total dose of bupivacaine was 23.1 ml (n = 35) and of ropivacaine 23.7 ml (n = 37). There was no significant difference between the groups in the profile of sensory block produced. There was no significant difference in the time of onset, or intensity of motor block between the groups but the duration of motor block was significantly shorter in the ropivacaine group. There was no significant difference in neonatal outcome, as assessed by Apgar score, umbilical cord blood-gas tensions at delivery or the neurological and adaptive capacity score 2 and 24 h after delivery. PMID- 7772424 TI - Prophylactic i.m. ephedrine in bupivacaine spinal anaesthesia. AB - In a double-blind, placebo-controlled, randomized study, we have investigated the efficacy of i.m. ephedrine in 98 elderly patients undergoing hip arthroplasty under spinal anaesthesia with plain bupivacaine. Fifty patients received ephedrine 0.6 mg kg-1 body weight, deep in the paravertebral muscles immediately after injection of bupivacaine, and 48 received an equal volume of saline. Patients in both groups were given the same volumes of fluid before anaesthesia. Systolic arterial pressure during the first 60 min after anaesthesia remained significantly more stable in the ephedrine-treated group, and there was also a significantly smaller number of patients in this group who had decreases in pressure of more than 30% of pre-block levels, and fewer required rescue i.v. ephedrine. An increase in heart rate or systolic pressure of > or = 20% from baseline was found in two patients in the ephedrine group and in one patient in the placebo group. We conclude that ephedrine 0.6 mg kg-1 body weight administered in the paravertebral muscles immediately after plain bupivacaine spinal anaesthesia is a simple and effective means of reducing the incidence of hypotensive episodes in the elderly patient. PMID- 7772425 TI - Cricoid pressure impedes placement of the laryngeal mask airway. AB - We have studied 22 patients to examine whether or not cricoid pressure affects ventilation of the lungs via the laryngeal mask and its correct positioning. In a randomized, crossover design, the laryngeal mask was inserted with or without cricoid pressure applied with a standardized force of 30 N using a cricoid yoke. A standardized pillow (6 cm in height) was placed under the patient's occiput, but the neck was not supported. Ventilation of the lungs via the laryngeal mask was adequate in all patients when no cricoid pressure was applied, but in only three of 22 patients when cricoid pressure was applied (P << 0.001; 95% confidence interval (CI) 0.72-1.0). The mask was positioned correctly in 18 patients when no pressure was applied, and in none after application of cricoid pressure (P << 0.001; 95% CI 0.66-0.98). We had planned to study, in an additional 20 patients, the effect of cricoid pressure without a pillow under the occiput; placement of the mask, however, was difficult even when cricoid pressure was not applied and there was a high incidence of bleeding from the oropharynx. We thus abandoned that part of the study after eight patients. In those eight patients, the success rate of ventilation via the laryngeal mask was lower when cricoid pressure was applied. We conclude that when sufficient force was applied, cricoid pressure, regardless of the method of application, did impede placement of the laryngeal mask. PMID- 7772426 TI - Continuous infusion of nimodipine during coronary artery surgery: haemodynamic and pharmacokinetic study. AB - A continuous infusion of nimodipine 15 or 30 micrograms kg-1 h-1 was administered from the evening before operation to the second morning after operation to 14 patients undergoing elective coronary artery bypass grafting (CABG) surgery. Nimodipine was tolerated well by all seven patients who received the lower dose. However, of the seven patients who received the higher dose, in two patients the infusion had to be discontinued after induction of anaesthesia and immediately after surgery, respectively, because of excessive vasodilatation and hypotension. At steady state before cardiopulmonary bypass (CPB), total plasma nimodipine concentration was higher than expected on the basis of previous reports in non surgical subjects. Similarly, mean clearance of nimodipine was lower than predicted, that is 0.53 (range 0.40-0.72) litre kg-1 h-1. Initiation of CPB decreased total plasma nimodipine concentration, but the unbound plasma concentration did not decrease because of the increase observed in the free fraction of nimodipine in plasma. As evaluated in a separate closed extracorporeal circuit, nimodipine was sequestered into the circuit. Addition of stored whole blood to the priming solution attenuated this sequestration. It is concluded that clearance of nimodipine, as assessed before CPB at steady state, was reduced in patients undergoing CABG and receiving a continuous infusion of nimodipine. Using this finding of decreased clearance in designing infusion schemes of nimodipine for cardiac-surgical patients, it should be possible to predict more accurately the desired plasma nimodipine concentration and therefore reduce the possibility of unexpected haemodynamic responses. PMID- 7772427 TI - Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. AB - In this prospective, randomized, double-blind study, we have investigated the effect of an antifibrinolytic agent, tranexamic acid (Cyklokapron), on blood loss and transfusion requirements associated with total knee arthroplasty. Twenty-nine patients were allocated randomly to receive either tranexamic acid 15 mg kg-1 or an equal volume of placebo a few minutes before a tourniquet was deflated. Blood loss during surgery, in the recovery room and on the surgical ward was recorded, together with the number of units of blood transfused in hospital. Mean blood loss during surgery was 428 (SD 254) ml in the tranexamic acid group (n = 15) compared with 415 (244) ml in the placebo group (n = 13). In the recovery room the tranexamic acid group lost 127 (95) ml and the placebo group 576 (245) ml (P < 0.001). On the ward the respective volumes were 293 (200) ml and 558 (293) ml (P < 0.01). Total blood loss was 847 (356) ml in the tranexamic acid group and 1549 (574) ml in the placebo group (P < 0.001). During the hospital stay the treatment group received 1.5 (1.3) units of blood compared with 3.3 (1.8) in the control group (P < 0.005). Two patients in the placebo group experienced a thrombotic complication compared with none in the treatment group. We conclude that tranexamic acid reduced perioperative blood loss and transfusion requirements associated with total knee arthroplasty. PMID- 7772428 TI - Non-invasive estimation of venous admixture: validation of a new formula. AB - We have developed a computer program that estimates venous admixture (intra pulmonary shunt) from four measurements: haemoglobin concentration, end-tidal carbon dioxide tension (PE'CO2), fractional inspired oxygen concentration (FIO2) and pulse oximetry (SpO2). The formula was tested on patients in an intensive therapy unit by using it to estimate shunt while it was measured simultaneously by a standard, invasive method. A total of 101 measurements were made in 29 patients. After correcting the systematic errors in the assumed differences between PE'CO2 and arterial PCO2, and between SpO2 and co-oximetrically measured SaO2, and correcting for a trend in the arteriovenous oxygen concentration difference (C(a-v))2) with shunt, the bias of the non-invasive minus invasive shunt differences was negligible, with no significant dependence on shunt. The limits of agreement were then +/- 16% shunt overall (+/- 13% within patients). When SaO2 was used instead of SpO2, the limits were +/- 11% (+/- 8% within patients). PMID- 7772429 TI - Halothane affects ventilatory afterdischarge in humans. AB - In awake humans, when ventilatory stimulation is suddenly removed, the subsequent change in minute ventilation (which remains at higher levels for longer times than expected from the dynamics of the chemoreceptors) is termed ventilatory after discharge. In this study we investigated the effects of subanaesthetic concentrations of halothane on afterdischarge. The ventilatory pattern after sudden termination of brief periods (90-180 s) of isocapnic hypoxia (PE'cO2 approximately 0.1 kPa above initial resting values; PE'O2 6.5 kPa) by normoxia (PE'O2 14 kPa) was determined in healthy volunteers. Six subjects underwent 13 studies without halothane (control) and six others 10 studies during inhalation of 0.22% halothane. Isocapnic hypoxia caused a mean increase in ventilation of 10.8 (SD 2.4) litre min-1 in the control and 4.2 (2.4) litre min-1 in the halothane studies (P < 0.01). The transition to normoxia caused a slow ventilatory decay in the control and a fast decay in the halothane groups: the interval that occurred between the "last hypoxic" breath and the time required for ventilation to return to 110% of baseline was 60.7 (23) s for the control and 12.3 (6.0) s for the halothane studies (P < 0.05). Taking into consideration the different factors that determine the pattern of breathing immediately after termination of a brief period of hypoxia by normoxia (PE'O2 waveform, transport delay time between lungs and carotid bodies, time constant of the peripheral chemoreflex loop and afterdischarge), the faster ventilatory decay observed with halothane is probably related to suppression of afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772430 TI - Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat. AB - Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to determine the possible selectivity of glycopyrronium for M2 and M3 muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates were characterized with [3H]-N-methylscopolamine ([3H]-NMS) by ligand binding studies. Inhibition of [3H]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine >> otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine >> HHSiD >> pirenzepine > otenzepad. These were similar to the expected order of frequency of M2 and M3 subtypes, respectively. Glycopyrronium showed similarly high affinities for both M2 (Ki = 1.889 (SEM 0.049) nmol litre-1) and M3 (Ki = 1.686 (0.184) nmol litre-1) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M2 or M3 muscarinic receptor subtypes. PMID- 7772431 TI - Potency of lipid and protein formulation of 5 alpha-pregnanolone at induction of anaesthesia and the corresponding regional brain distribution. AB - We have studied the anaesthetic potencies of 5 alpha-pregnanolone albumin solution (PAS) and 5 alpha-pregnanolone Intralipid emulsion (PLE) at equivalent concentrations in male rats using an EEG threshold method. The criterion of anaesthesia was burst suppression of the EEG of 1 s or more (the "silent second" (SS)) as a sign of deep anaesthesia. The potency of the two formulations was assessed by comparing the threshold doses of 5 alpha-pregnanolone at three dose rates (1.0, 2.0 and 3.0 mg kg-1 min-1). We found that SS was initiated in all rats after infusions of PAS, while no SS could be induced in rats after infusion of PLE at a larger dose. A higher concentration of 5 alpha-pregnanolone was found in all brain and peripheral tissues of PAS-treated rats than in those treated with PLE. In rats with PAS-induced anaesthesia (3.0 mg kg-1 min-1), the highest concentrations were detected in striatum (mean 19.40 (SD 1.21) ng mg-1). Although there was a small insignificant reduction in threshold doses with dose rates at 2.0-3.0 mg kg-1 min-1, the tissue concentrations in striatum, frontal cortex and occipital cortex were found to be significantly increased. We conclude that PAS was more potent than PLE in inducing anaesthesia. Brain distribution of 5 alpha pregnanolone varied regionally in a manner similar to the variation in GABAA receptor sensitivity to this neuroactive steroid. PMID- 7772432 TI - Human cytochrome P450 mono-oxygenase system is suppressed by propofol. AB - We have studied the effect of propofol on the cytochrome P450-dependent mono oxygenase system in human liver microsomes by assaying mono-oxygenase activities toward specific cytochrome P450 isoform test substrates, aniline, 7 ethoxycoumarin, benzphetamine and benzo(a) pyrene. Propofol inhibited benzo(a)pyrene hydroxylation to a greater extent than the oxidative metabolism of the other test substrates, even at 0.05 mmol litre-1. The degrees of inhibition of benzphetamine N-demethylation and 7-ethoxy-coumarin O-de-ethylation were similar, while aniline hydroxylation was least affected by propofol. Spectral analysis showed that propofol competed with carbon monoxide for binding to the haem moiety of haemoprotein in the P450 enzyme. The variable inhibition observed may be caused by the differential binding of propofol to P450 isoforms. Propofol 0.05-1.0 mmol litre-1 exhibited a concentration-dependent inhibitory effect on human cytochrome P450 2E1, 2B1 and 1A1. These inhibitory actions of propofol on human liver microsomal enzymes in vitro suggest that potential drug interactions may exist between propofol and other drugs administered clinically. PMID- 7772433 TI - ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart. AB - Sustained dysfunction of myocardial contractility after short periods of coronary artery occlusion and reperfusion has been termed "stunned myocardium". Isoflurane may improve the recovery of regional myocardial contractility in stunned myocardium. The purpose of the present study was to determine if isoflurane prevents depletion of high energy phosphates after myocardial ischaemia reperfusion and if the reduction in cardiac work during isoflurane anaesthesia contributes to the preservation of high energy phosphate metabolism in an acute canine model. Mongrel dogs were allocated to one of three groups: controls, anaesthetized with urethane and chloralose; ISO group, isoflurane administered before ischaemia; and ISOc group, heart rate and mean arterial pressure controlled to approximately match baseline values. The left anterior descending (LAD) coronary artery was occluded for 15 min and then reperfused for 60 min during 1.5% end-tidal isoflurane anaesthesia. Full thickness samples of myocardium were obtained from the reperfused area (supplied by the LAD) and the non-ischaemic area (supplied by the left circumflex coronary artery). The concentrations of adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), creatine phosphate (CP) and lactate in the endocardial portion of the myocardium were measured. Arterial pressure, aortic flow in the ascending aorta and rate-pressure product decreased significantly after isoflurane. Although the concentration of ATP of the reperfused area in the control group showed a significant reduction 60 min after reperfusion, the ISO and ISOc groups had significantly greater concentrations. Isoflurane anaesthesia maintained myocardial high energy phosphate metabolism in reperfused myocardium. We conclude that the reduction in cardiac work played only a minor role in the ATP-sparing effect of isoflurane. PMID- 7772435 TI - Effect of sevoflurane on the vascular reactivity of rabbit mesenteric artery. AB - Sevoflurane is well known to cause depression of cardiovascular function, but detailed information on its actions on the contractility and reactivity of blood vessels is lacking. We have assessed therefore the direct effect of this anaesthetic on the functional reactivity of isolated rabbit mesenteric artery ring preparations. We found that contractions of endothelium intact rings induced by noradrenaline and phenylephrine were significantly attenuated by 4% sevoflurane; the observation that the maximal tension generation decreased without a significant reduction in pD2 is consistent with the view that receptor dysfunction was not involved. The effect of sevoflurane was not affected by NG monomethyl-L-arginine. Sevoflurane 4% also produced attenuation of noradrenaline induced contractions of endothelium denuded ring preparations. The contractions of endothelium denuded ring preparations produced by noradrenaline in Ca(2+)-free media in the presence of K+ were not affected by 4% sevoflurane, but sevoflurane depressed external Ca(2+)-dependent contractions. When vasodilators (acetylcholine and nitroglycerin) were added to the bathing media in the presence of 2% sevoflurane, the endothelium-dependent relaxation produced by acetylcholine, but not the endothelium-independent relaxation produced by nitroglycerin, was attenuated; superoxide dismutase inhibited the effect of sevoflurane on endothelium-dependent relaxation. These results are consistent with the view that sevoflurane inhibits alpha adrenoceptor-mediated contractions of isolated rabbit mesenteric artery ring preparations; this effect may be caused by reduced Ca2+ influx, as estimated from the effect on external Ca(2+)-dependent contractions, but is unlikely to be caused by reduced Ca2+ release from the sarcoplasmic reticulum of vascular smooth muscle, as estimated from noradrenaline induced contractions in Ca(2+)-free bathing media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772434 TI - Comparative effects of halothane, enflurane, isoflurane and sevoflurane on function and metabolism in the ischaemic rat heart. AB - This study was designed to examined the effects of inhalation anaesthetics on function and metabolism in isolated ischaemic rat hearts. Four volatile anaesthetics in two different concentrations (1.0 to 1.5 MAC) were used before whole heart ischaemia was induced for 15 min followed by reperfusion for 30 min. The data were compared with a control group in which inhalation anaesthetics were not used. Before ischaemia, volatile anaesthetics depressed ventricular function. During reperfusion, ventricular function and coronary flow in both halothane groups were significantly lower than those in the control group. Myocardial ATP concentrations in the 1.0 MAC of enflurane and isoflurane groups were significantly higher than those in the control group. We conclude that halothane had more depressant effects than the other anaesthetics and that enflurane and isoflurane may enhance metabolic recovery in the ischaemic working rat heart. PMID- 7772436 TI - Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs. AB - We have studied the cardiovascular effects of incremental doses of three catecholamines in dogs subjected to lactic (LAC) and hydrochloric (HCl) acidosis. Fifty-four dogs were allocated randomly to one of three groups: control, LAC and HCl acidosis (n = 18 each group). In the acidotic models, 2 mol litre-1 of lactic acid (4 ml kg-1 h-1) or 2 mol litre-1 of HCl (1 ml kg-1 h-1) was infused i.v. until arterial pH was reduced to 7.00 +/- 0.1. Within each group, six dogs received one of three different drugs in logarithmically incremental doses: adrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 micrograms kg-1 min-1, noradrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 micrograms kg-1 min-1 and dobutamine 5, 10, 20, 40, 80, 160 micrograms kg-1 min-1. Cardiovascular variables were monitored, with periodic measurements of plasma electrolyte and lactate concentrations. The pH reduction induced by HCl or lactic acid was associated with a statistically significant increase in mean pulmonary arterial pressure (MPAP), prominent especially in the LAC group where MPAP increased from mean 18 (SD 5) to 27 (6) mm Hg. In the acidotic models, the reduction in myocardial responsiveness to adrenaline or noradrenaline was more prominent than that for the control for corresponding doses of drugs. In the LAC group mean cardiac index decreased significantly from 5.2 (1.8) to 2.2 (0.7) litre min-1 m-2 after infusion of adrenaline 3.2 micrograms kg-1 min-1 and decreased from 5.1 (1.1 to 2.4 (0.9) litre min-1 m-2 after infusion of noradrenaline 3.2 micrograms kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772437 TI - Gastric intramucosal pH, tissue oxygenation and acid-base balance. PMID- 7772438 TI - Comparison of three devices for oxygen administration in the late postoperative period. AB - We have evaluated three different devices for oxygen administration in the surgical ward, the Hudson face mask (oxygen 3 litre min-1, air 12 litre min-1), the nasal prong (oxygen 3 litre min-1) and the binasal catheter (oxygen 3 litre min-1). We evaluated the three devices in random order for periods of 30 min each in 25 patients with postoperative hypoxaemia (SpO2 < or = 94%). Arterial oxygen saturation was measured by continuous pulse oximetry and comfort was evaluated with a questionnaire after each treatment period. The three systems increased arterial oxygen saturation to similar levels, but the highest degree of comfort was found with the binasal catheter. Use of the binasal catheter is recommended for oxygen administration in the late postoperative period. PMID- 7772439 TI - Effect of i.v. diamorphine on the regression of spinal block. AB - Twenty patients undergoing transurethral prostatectomy under spinal anaesthesia were allocated randomly in one of two groups. After operation dermatomal levels to cold were measured every 30 min until they had receded to T10. Patients in group 1 were then given diamorphine 5 mg in 0.9% saline 5 ml i.v. and in group 2 0.9% saline 5 ml i.v. Block level to cold and degree of motor block were assessed at 15-min intervals for 1 h after injection. Block regression continued in the control group while there was no decrease in the diamorphine group for 30 min (P < 0.01) after which it then receded at a similar rate as the control group. There was no significant difference in motor block between the two groups. PMID- 7772440 TI - Intra-vas deferens bupivacaine for prevention of acute pain and chronic discomfort after vasectomy. AB - We have studied the use of intra-vas deferens local anaesthesia in 70 patients undergoing vasectomy as day-case patients. Patients were allocated randomly to either a control or treatment group. In the treatment group, 0.5% bupivacaine 1 ml or 0.9% saline 1 ml was injected into the lumen of the right or left vas deferens in a randomized blinded design. The control group did not receive an injection. Patients were discharged with a questionnaire for recording visual analogue scores (VAS) for both the right and left sides to be scored on days 1 and 7 after operation. One year after the procedure a second questionnaire was sent out asking about the presence or absence of chronic testicular discomfort, its duration and any surgical intervention required to relieve it. There were no differences between the control group and the saline side of the treatment group in VAS scores on both day 1 and day 7 after operation or in the incidence and duration of chronic testicular discomfort (mean 30 (SD 53) and 34 (50) days, respectively). The VAS scores were, however, significantly less (P < 0.005) and testicular discomfort was absent on the bupivacaine-treated side. PMID- 7772441 TI - Lansoprazole in the prophylaxis of acid aspiration during elective surgery. AB - We have assessed the efficacy of a single dose of lansoprazole in increasing the pH and decreasing the volume of gastric residue at induction of anaesthesia in adult patients undergoing elective orthopaedic surgery. We studied 66 ASAI-II patients, allocated to one of three groups to receive either placebo (group 1), lansoprazole 30 mg (group 2) or lansoprazole 60 mg (group 3), 8-12 h before induction of anaesthesia. Volume and pH of gastric contents were measured after induction of anaesthesia by aspiration via a 16-French gauge gastric tube. Patients who received lansoprazole had a significantly higher pH than the placebo group (P < 0.01) but there was no difference between the two lansoprazole groups. The volume of gastric residue was significantly smaller (P < 0.01) in both lansoprazole groups compared with the placebo group: 28% of those in group 3 had a pH of gastric residue < 2.5 and volume > 25 ml compared with 30% in group 2 and 63% in group 1, respectively. PMID- 7772442 TI - Hyperventilation reverses the nitrous oxide-induced increase in cerebral blood flow velocity in human volunteers. AB - Because hypocapnia is routine during general anaesthesia for intracranial procedures, we have compared, in 13 healthy volunteers, the effect of normocapnia (PE'CO2 5.3 kPa) and hypocapnia (PE'CO2 3.3 kPa) on mean blood flow velocity in the middle cerebral artery (Vmca) during normoventilation and hyperventilation with air and with 50% nitrous oxide in oxygen. After replacement of air with 50% nitrous oxide in oxygen, there was an increase in mean Vmca during normoventilation (air: mean 68.23 (SD 16.98) cm s-1 vs nitrous oxide in oxygen: 90.69 (20.41) cm s-1; P < 0.01), whereas during hyperventilation mean Vmca values were similar regardless of the inhaled gas mixture (air: 43.46 (9.97) cm s-1 vs nitrous oxide in oxygen: 41.69 (8.08) cm s-1. Our data suggest that the nitrous oxide-induced increase in mean Vmca can be blocked by hyperventilation. PMID- 7772443 TI - Effect of automatic record keeping on vigilance and record keeping time. AB - We have evaluated the effect of an automatic anaesthesia record keeper (AARK) on record keeping time and vigilance. With informed patient consent and institutional approval, we videotaped the attending anaesthetist and his/her immediate surroundings during 66 surgical procedures. Thirty-seven cases were charted manually and the remaining 29 were charted with a commercially available AARK. In order to evaluate vigilance, a physician examiner entered the operating room unannounced once during 33 of the manually charted cases and during 22 of the automatically charted cases and asked the anaesthetist to turn away from the monitors and recall the current value of eight patient physiological variables. The examiner recorded the recalled values and also the actual current monitor values of these variables. The videotapes were reviewed and the anaesthetist's intraoperative time was categorized into 15 predefined activities, including intraoperative anaesthesia record keeping time. We compared recalled and actual variable values to determine if the recalled values were within clinically relevant error limits. There was no statistical difference between the mean percentage case time spent recording manually (14.11 (SD 3.98)%) and automatically (12.39 (3.92)%). Moreover, use of the AARK did not significantly affect vigilance. Despite major advances in monitoring technology over the past 14 years, record keeping still occupies 10-15% of the anaesthetist's intraoperative time. It appears that in using an AARK, the anaesthetist reallocates intraoperative record keeping time from manual charting to dealing with problems in the anaesthetist machine interface caused by inadequate design. PMID- 7772444 TI - Circumcision analgesia. PMID- 7772445 TI - Fresh gas flow rate and enflurane consumption. PMID- 7772447 TI - Methoxamine and blood loss in prostatic surgery. PMID- 7772446 TI - Methoxamine and blood loss in prostatic surgery. PMID- 7772448 TI - Posture and autonomic cardiac control. PMID- 7772449 TI - Hyperventilation-induced unconsciousness during labour. PMID- 7772450 TI - Nitric oxide delivery system. PMID- 7772451 TI - Nitric oxide delivery system. PMID- 7772452 TI - Help-seeking for AIDS high-risk sexual behavior among gay and bisexual African American men. AB - Help-seeking for AIDS high-risk sexual behavior and its association with HIV status were examined among 318 gay and bisexual men in the San Francisco Bay Area who participated in the African American Men's Health Project, a longitudinal survey of gay and bisexual African-American men. A third (36%) of the sample reported seeking help regarding their concerns about HIV high-risk sexual behavior. Peers and professionals were the most widely sought sources of help and the sources perceived to be the most helpful. Men (39%) who had received the HIV antibody test and who were HIV seropositive were more likely to seek help than men who were HIV seronegative or did not know their HIV status (25%). Furthermore, gay men who were HIV seropositive or who knew their serostatus were more likely to seek help from professionals and peers. Explanations for the differences in help-seeking by HIV-seropositive men are discussed with implications for the development of social support for HIV risk reduction among gay and bisexual African-American men. PMID- 7772453 TI - Planning and evaluating strategies for AIDS health education interventions in the Muslim community in Uganda. AB - In 1992 the Islamic Medical Association of Uganda designed an AIDS prevention project. A baseline survey was conducted to assess prevailing knowledge, attitudes, and practices among the Muslim communities in two districts. A low rate of incorrect beliefs about HIV transmission was found, although gaps in knowledge remain, particularly regarding vertical transmission and asymptomatic HIV infection. Less than 10% knew that condoms can protect against HIV transmission. Lack of knowledge was documented regarding the risk of HIV transmission associated with practices common in the Islamic community, such as polygamous marriages, circumcision, and ablution of the dead. The AIDS prevention project has incorporated specific messages and interventions as a result of these findings. PMID- 7772454 TI - HIV risk behavior among homeless adults. AB - Very little information is available regarding HIV risk behavior among homeless adults despite increasing evidence that HIV infection disproportionately affects inner-city residents and disadvantaged populations. In the present study, adults (N = 94) entering a storefront medical clinic for the homeless completed an AIDS risk survey. The results suggest that homeless adults are engaging in sexual and substance-use behaviors that place them at high risk for HIV infection. Sixty nine percent of the present sample was at risk for HIV infection from either 1) unprotected intercourse with multiple partners, 2) intravenous drug use (IVDU), 3) sex with an IVDU partner, or 4) exchanging unprotected sex for money or drugs. Many persons within the sample evidenced multiple risk factors: 45% reported at least two of the risk factors described above and 26% reported three or more risk factors. The results suggest there is an urgent need to develop and evaluate AIDS prevention strategies for homeless adults. PMID- 7772455 TI - Health belief and self-efficacy models: their utility in explaining college student condom use. AB - This investigation tested the ability of the Health Belief Model (HBM), dimensions of self-efficacy, various behavioral variables (i.e., number of sex partners in the past 12 months, frequency of drunkenness during sexual intercourse, and number of diagnosed sexually transmitted diseases), and demographic measures to distinguish between three condom user groups (i.e., nonusers, sporadic users, and consistent users). The usable sample consisted of 366 college students, ages 18 to 24. The study operationalized the following HBM components: perceived susceptibility, perceived benefits, and perceived barriers. The multidimensional Condom Use Self-Efficacy Scale (CUSES) was also used in this investigation. Results from a discriminant analysis indicated that sporadic users were best distinguished from both consistent and nonusers by number of sex partners in the past year, frequency of drunkenness during sexual intercourse, perceived susceptibility to HIV/AIDS and other STDs, and a self-efficacy factor labeled Assertive. The sporadic users had significantly more sex partners, were drunk more often when engaging in sexual intercourse, perceived themselves as more susceptible to HIV/AIDS and other STDs, and were less confident in their ability to discuss and insist on condom use with a partner. It was also discovered that each condom user group was best defined by different subsets of discriminating variables. Implications of these findings for campus-based prevention programs and future research are discussed. PMID- 7772456 TI - Behavioral training and AIDS risk reduction: overcoming barriers to condom use. AB - To assess the short- and long-term effects of an AIDS-prevention workshop on undergraduates' attitudes about condom use and AIDS, 31 participants and 31 controls were studied immediately after training sessions as well as three months later. The workshop was aimed at reducing embarrassment to purchase condoms, encouraging positive attitudes about condoms, and promoting knowledge about AIDS. To help students overcome their embarrassment over condom purchases, a behavioral intervention was included allowing students to make condom purchases at nearby drug stores. Results revealed that participants reported less embarrassment over condom purchases after training sessions and that this effect became even stronger over time. Knowledge about AIDS and positive attitudes about condoms also increased immediately after the workshop, but these changes did not persist. Results suggest that AIDS prevention workshops may lead to transient changes unless a specific skill (i.e., condom purchasing) is targeted via behavioral training. PMID- 7772457 TI - Using students' salient beliefs to design an instructional intervention to promote AIDS compassion and understanding in the middle school. AB - This article documents the construction and validation of a videotaped message to persuade middle school students to volunteer as the laboratory partner of a classmate who has AIDS. Based on well-established social-psychological models of persuasion, message arguments are designed either to reinforce or to downplay the modal salient beliefs held by message recipients about the intended behavior. The end-product of this precisely tailored, six-step process is instruction which not only promotes the adoption of tolerant and compassionate attitudes, but also provides an opportunity for the practice of essential life skills such as decision making and problem solving. The process itself is offered as a model for designing any instructional material which addresses today's growing list of AIDS related issues having both moral and ethical implications. PMID- 7772458 TI - Determinants of safe and risk-taking sexual behavior among gay men: a review. AB - Since the outbreak of the AIDS epidemic, gay men have made impressive changes in their sexual behavior. Notwithstanding these changes, there are several studies that show considerable within-subject variability in risk categories, indicating that for a substantial number of gay men it is difficult to be consistently safe. A large number of studies have examined the relationship between sexual behavior and determinants of that behavior. This review reports and discusses the findings with regard to demographic, situational, behavioral, and psychosocial determinants. PMID- 7772459 TI - Samuel Broder, MD, resigns as NCI Director: a highly effective champion of cancer education. PMID- 7772460 TI - Can practicing physicians improve their counseling and physical examination skills in breast cancer screening? A feasibility study. AB - OBJECTIVE: To improve breast cancer screening skills, practicing non-academic primary care physicians were offered an opportunity to participate in a one-hour private skills-assessment session with a patient instructor. Research questions included: would physicians in non-academic practice be interested in a skills course; would the course improve their skills in breast examination and/or in counseling for mammography; and if they did improve, would the effect endure? DESIGN: Pilot study with cohort follow-up. INTERVENTIONS: Physicians were offered an opportunity to have their counseling and physical examination skills evaluated in a one-on-one interaction with standardized patients. The protocol included patient instructors who were trained to use a uniform breast health history that emphasized their increased risk of breast cancer, scant knowledge of breast cancer screening, and fear of medical tests and cancer. The standardized patients were trained using a 77-point checklist. They demonstrated a high degree of consistency and reproducibility. A critical part of the learning experience was immediate feedback to the physicians regarding their performances. Physicians who took the course were given an opportunity to repeat it approximately 18 months later. MEASUREMENTS AND MAIN RESULTS: Of the 82 primary care physicians in the community, 49 (60%) were eligible to have their skills evaluated. Of these, 38 (77.6%) participated in the intervention. Baseline skills had mean scores (correct responses) better than 50% in most aspects of the physical examination but less than 35% in several critical counseling areas: reviewing mechanics of getting mammography, actually recommending mammography, and directing the patient regarding scheduling. Of the 38 physicians, 15 repeated the course. There was a significant improvement in their overall performance: 49% vs 67% (p = 0.002). CONCLUSIONS: Primary care physicians in a non-academic practice are interested in reviewing and improving their counseling skills. They are capable of improving their skills after receiving background information, instruction, and brief feedback. They maintain these improvements over time. PMID- 7772461 TI - Breast cancer screening practices for hospitalized women. AB - The increasing prevalence of breast cancer and the demonstrated benefits of routine breast screening activities have prompted considerable attention to the use of screening procedures. In addition to public education efforts, physicians have been encouraged to incorporate breast screening guidelines into their daily practice. This study was undertaken to examine the current practice of breast screening activities for women hospitalized on a general medical or surgical unit at a university medical center. A retrospective chart review of 159 women hospitalized during a six-month period demonstrated that breast screening activity in the sample was similar to national rates of breast cancer screening. Within the year, 43% of these women had had a clinical breast examination and 21% had had mammography. This suggests that the period of hospitalization had not been used by practitioners as an opportunity to initiate breast screening activities in the patient's care. PMID- 7772462 TI - Low-cost flexible sigmoidoscopy screening: a community demonstration and education project. AB - The purpose of this project was to demonstrate that a low-cost, community-based screening and education approach (for both patients and physicians), as has been used with mammography, can be successful with flexible sigmoidoscopy. One hundred appointments over four days were made available via a targeted mailing to 12,000 health-interested community members if they were asymptomatic, 50 years old or older, and had never before been screened by flexible sigmoidoscopy. The cost for the procedure was set at $50. Professional education was accomplished by having local physicians interested in gaining greater experience with flexible sigmoidoscopy provide the screenings under supervision. All 100 patient appointments and seven physician-training slots were quickly filled. Ninety-five procedures were performed by seven local physicians, averaging 10 minutes per procedure, with an average insertion depth of 31 cm and a 4.2% premalignant-polyp detection rate. The patients were also given education and counseling about colorectal cancer screening and prevention, and were evaluated by pre- and post testing, and satisfaction questionnaires. The patients demonstrated markedly significant knowledge gains about colorectal cancer prevention and early detection, with 99% agreeable to having the procedure repeated in the future. This project demonstrated a high level of both public and professional willingness to participate in a flexible sigmoidoscopy screening program. The project method is presented in detail to encourage future such programs. PMID- 7772463 TI - Evaluation of alternate messages on an electronic message strip to recruit subjects to a smoking-cessation program. AB - The authors previously published details of a method to evaluate the effectiveness of electronic message strips in recruiting subjects to a smoking cessation program. They now report data suggesting that a shorter, more negative message yields better results than a longer, more positive message. The data also show that this approach increases the number of subjects who enroll in a smoking cessation program and the number of subjects who actually quit smoking. PMID- 7772464 TI - The carcinogenic risks of alcoholic beverages: implications for cancer education. AB - The proper analysis of the data generated by studies of carcinogenic risks of drinking alcoholic beverages would be the application of models from the relatively new approach of meta-analysis. In this study, 441 articles were generated by a 1992 MEDLINE search of the key words "alcohol drinking" and "cancer." Of these, only 29 met the criteria for a formal meta-analysis. For these 29 research reports, the 95% confidence limits for the odds ratio were 1.28 and 1.15, suggesting a weak association between drinking and cancer. This conclusion was rendered even less decisive by the following problems in the studies analyzed: 1) absence of comparable measures of either dosages or drinking patterns; 2) absence of comparable methods of data analysis; 3) absence of comparable measures of other population characteristics; and 4) widely varying results from study to study. For example, the 95% confidence limits for the odds radio of the 16 European studies were 1.14 and 0.98, indicating not even a reliable directional difference between drinking and nondrinking populations. Although the World Health Organization International Agency for Research on Cancer concluded in 1987 that alcoholic beverages are carcinogenic, the scientific literature extant in 1992 provides only very weak support for that finding. There is a need for multiple nonexperimental investigations using methods that will produce results sufficiently comparable to justify the application of the statistical models being generated for the meta-analysis of important questions not subject to direct experimentation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772465 TI - A survey to determine the knowledge of military members about the hazards of tobacco use, and a resulting tobacco-hazard education project. AB - A questionnaire and an intraoral examination were administered to 340 U.S. Navy personnel in order to ascertain the use of tobacco and its effect within the oral cavity. The rate of tobacco use among these military personnel was about twice that of the general public. About 45% of the patients were not well informed of the systemic or intraoral hazard of tobacco usage. With a need for tobacco-hazard awareness documented, an educational project was designed and administered to over 4,000 military and civilian participants. This education program has now been expanded to train health care professionals so that they can perform their own tobacco-hazard education with patients and small groups. PMID- 7772467 TI - Cancer education and the primary school teacher in England and Wales. AB - Many adult behaviors and attitudes develop in early childhood. There is a growing acceptance of the need for health education of children of primary school age. Cancer is an important topic within health education, and this study was designed to assess the level of cancer education in schools. Data were collected from a randomly selected sample of over 1,000 teachers of children in primary school years 3-6 (ages 7-11 years). Cancer had been taught about by 18% of the sample, and their pupils' ages had no significant effect on whether they had taught about cancer. Cancer was most often taught about in response to a real-life situation, and the majority of the teachers did not use cancer education resources to help them. The study sought to ascertain why so many teachers had taught about cancer. It appears that concerns over their own lack of personal knowledge, and a perceived lack of resources, were the most common reasons. The young age of the pupils was also a deterrent to cancer education, especially among the teachers of the younger pupils. The results indicate various interventions that may increase the level of primary-school-based cancer education. These include improving teachers' awareness of cancer education issues and providing appropriate cancer education resources. PMID- 7772466 TI - Oncology education needs survey of registered nurses in Texas. AB - In response to the need to determine continuing education priorities in oncology nursing, the Nurse Oncology Education Program surveyed a geographically stratified random sample of Texas registered nurses concerning their oncology practices, perceived skill levels, and personal needs for training in 61 topics areas. The 378 respondents rated their skill levels low to medium, although 62% cared directly for patients with cancer. The highest-rated priorities for professional education were: legal issues, issues and trends in cancer care, investigational/new drug development, and bone marrow transplantation. Nurses employed in community settings and those living outside metropolitan areas tended to indicate the highest numbers of strong training needs. However, comparison of the needs for cancer prevention and detection education by regions showed that for none of the geographic regions was a high training need for cancer prevention and detection identified. PMID- 7772468 TI - Problem-based learning: innovative approach to studying chronic disease in dentistry. PMID- 7772469 TI - Improving residents' knowledge of cancer prevention: are physicians prepared for prevention? AB - BACKGROUND: Primary care physicians recognize the goal of integrating cancer prevention strategies into clinical practice. However, there is little formal training in cancer prevention and early detection. This study describes the effectiveness of a cancer-prevention curriculum called "Recommendations for Cancer Prevention (ReCaP) for Residents" for primary care residency programs. METHODS: The ReCaP for Residents curriculum was organized into eight instructional modules by organ site-specific areas for which there are established primary and secondary cancer-prevention recommendations. The modules include content outlines, learning objectives, slides, and case studies. In-house faculty and 21 residents of two family practice programs participated in an intervention comprising seven one-hour modular presentations during their regular summer teaching program. An established cancer-prevention knowledge test with 100 test items was used to test the residents' knowledge before and after the intervention; the data were analyzed by factor analysis with principal-component extraction and varimax rotation. RESULTS: The residents knew significantly more about cancer prevention after the ReCaP for Residents program. The mean overall prevention knowledge increased significantly (p < .05), and the scores of six of eight specific organ-site areas also increased. CONCLUSION: This study provided evidence that ReCaP for Residents was an effective curriculum for increasing residents' knowledge of cancer prevention. The authors recommend that more extensive programs of this type be implemented. PMID- 7772470 TI - Biological activity of vitamin D analogues in the skin, with special reference to antipsoriatic mechanisms. AB - Active vitamin D3 modulates epidermal growth, keratinization and inflammation, and various vitamin D3 analogues have been shown to be effective in the treatment of psoriasis. These analogues now provide a useful addition to the therapeutic modalities available for the treatment of psoriasis. Epidermal hyperproliferation, abnormal keratinization and inflammation are the well established hallmarks of the psoriatic plaque. The aim of this review is to provide an update of information on the cell biological effects of vitamin D3, and the influence of vitamin D analogues on the pathomechanisms of psoriasis. PMID- 7772471 TI - Overview of the use of terbinafine (Lamisil) in children. AB - This review summarizes the efficacy and tolerability of terbinafine (Lamisil) in the treatment of dermatophytoses in children. In six clinical studies, 152 children who received terbinafine were evaluable for efficacy and 196 were evaluable for tolerability. In these studies, terbinafine was used for between 1 and 28 weeks. The median treatment was 4 weeks, the duration of treatment in the tinea capitis studies. As a result of extensive experience in adults at doses of 10 mg/kg and less, and the overall pharmacokinetic profile in children, including the lower volume of distribution of terbinafine into lipophilic tissue, the use of a dose of 125 mg/day for children weighing 20-40 kg, and 62.5 mg/day in children weighing less than 20 kg, has been proposed. This dose was shown to be well tolerated and effective. For children weighing > 40 kg, the adult dose of 250 mg is appropriate. Terbinafine was shown to be very effective (93% cured), in the treatment of children with tinea capitis, using a shorter treatment duration (4 weeks) than that usually employed with presently available antifungal drugs. It is also effective in children with various dermatophyte infections of the skin, with a cure rate of more than 90%. Terbinafine was shown to be well tolerated in children aged between 2 and 17 years. The recommended duration of treatment for tinea capitis is 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772472 TI - Reduced wound contraction and scar formation in punch biopsy wounds. Native collagen dermal substitutes. A clinical study. AB - In full-thickness skin wounds dermal regeneration usually fails, resulting in scar formation and wound contraction. We studied dermal regeneration by implantation of collagenous matrices in a human punch biopsy wound model. Matrices were made of native bovine collagen I fibres, and either hyaluronic acid, fibronectin, or elastin was added. Matrices were placed in 6-mm punch biopsy holes in seven patients (biopsies were used for the grafting of leg ulcers), and covered with a protective semi-permeable polyether urethane membrane. Histology, wound contraction and dermal architecture were studied. Dermal architecture was evaluated using a recently developed laser scatter technique. All collagen matrices showed a tendency to reduce wound contraction, compared with control wounds; elastin- and fibronectin-treated matrices showed significantly less contraction than control wounds. Only the addition of elastin had a clear beneficial effect on dermal architecture; collagen bundles were more randomly organized, compared with control wounds, and wounds treated with collagen matrices coated with fibronectin or hyaluronic acid, or without coating. We conclude that the punch biopsy wound model provides important information on dermal regeneration in humans. Native collagen matrices with elastin contributed to dermal regeneration and reduced wound contraction, in contrast with matrices coated with fibronectin or hyaluronic acid, or without coating. Future clinical studies of large-area, full-thickness wounds will be required to establish their clinical relevance for leg ulcer and burn treatment. PMID- 7772473 TI - Failure of intradermal skin testing with gluten to produce delayed hypersensitivity reactions in patients with dermatitis herpetiformis. AB - Dermatitis herpetiformis (DH) is characterized by a rash and a gluten-sensitive enteropathy (GSE) indistinguishable from that of coeliac disease. T-cell-mediated mechanisms have been implicated in the pathogenesis of GSE. It seems feasible that intradermal injection of gluten, in patients known to have GSE, could lead to an influx of T cells sensitized to gluten, with subsequent development of a delayed hypersensitivity-type reaction. Six patients with DH and three normal subjects had intradermal injections of 'Frazer's fraction III' (FFIII; the partial peptic tryptic digest of gluten which is known to be antigenic) and phosphate-buffered saline (PBS) as a control. Skin biopsies were taken at PBS and FFIII injection sites at 48 h. In addition, two of the patients with DH had biopsies taken of FFIII injection sites at 6 h. Monoclonal antibodies and the avidin-biotin-peroxidase technique were used to stain for T cells in the skin biopsies. A monoclonal antibody to a neoepitope exposed in the terminal complement complex and an immunofluorescent method were used to detect the presence of terminal complement component in biopsies taken from two of the control subjects and two of the patients. Both patients and control subjects developed a weal and flare within a few minutes of injecting the FFIII, and this persisted for up to 6 h. No skin reaction was present in either the patients or the control subjects at 48 h. No skin reaction was visible at any time following injection of PBS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772474 TI - Effects of cyclosporin and ultraviolet radiation on growth and ornithine decarboxylase activity in cultured human epidermal keratinocytes. AB - Both cyclosporin (CyA) and ultraviolet radiation are effective in the treatment of psoriasis, but their precise mechanisms of action are uncertain. We investigated their effects on ornithine decarboxylase (ODC) activity, ODC gene expression, and cellular proliferation stimulated by epidermal growth factor (EGF), in cultured normal human epidermal keratinocytes. CyA (5 micrograms/ml) inhibited ODC activity, ODC mRNA level, and cell growth induced by 50 ng/ml EGF. Ultraviolet B (10 mJ/cm2) irradiation suppressed the induction of ODC, ODC mRNA, and cell proliferation stimulated by EGF, but ultraviolet A (0-15 J/cm2) irradiation inhibited neither EGF-stimulated ODC activity nor cell proliferation. These findings indicate that reduction of ODC activity in CyA- or ultraviolet B treated human keratinocytes may contribute to the antiproliferative mechanism of these agents. These results also suggest that the regulation of ODC activity by ultraviolet B and A irradiation may be mediated by different signal transduction pathways. PMID- 7772475 TI - Localization of anionic sites in normal and psoriatic epidermis: the effect of enzyme digestion on these anionic sites. AB - Cell surface anionic charge is known to be related to various cellular functions. Therefore, we ultrastructurally localized anionic sites in normal and psoriatic human epidermis, using poly-L-lysine-gold complex (cationic gold), to assess their possible participation in the differentiation of keratinocytes and the pathogenesis of psoriasis. In normal and psoriatic epidermis, the cell membrane of keratinocytes showed positive staining at pH 2.0. At pH 7.4 the cytoplasm and nucleus were diffusely stained, in addition to the cell membrane. In normal epidermis, the intensity of labelling on the cell membrane at pH 2.0 was strong in the basal layer and lower stratum spinosum, and decreased in parallel with differentiation of keratinocytes. In psoriatic epidermis, the intensity of labelling on the cell membrane at pH 2.0 was stronger than in normal epidermis. In normal epidermis, heparitinase digested 63% and chondroitinase ABC digested 80% of cationic labelling. This suggests that heparan sulphate and chondroitin sulphate (and/or dermatan sulphate) constitute anionic sites in normal epidermis. In psoriatic epidermis, chondroitinase ABC-sensitive anionic sites were greatly increased, whereas heparitinase-sensitive anionic sites were the same, when compared with normal epidermis. This suggests that chondroitin sulphate and/or dermatan sulphate constitute anionic sites which are increased in psoriatic epidermis. PMID- 7772476 TI - Electrical impedance measured to five skin depths in mild irritant dermatitis induced by sodium lauryl sulphate. AB - The non-invasive electrical impedance technique used in this study reflects structural changes in a tissue, and provides an estimate of the level of oedema by a simple impedance index. Sodium lauryl sulphate (SLS), dissolved in water at concentrations of 0.1, 0.5 and 2.0%, was applied for 24 h in 12 mm Finn chambers on both volar forearms of 12 healthy volunteers. An unoccluded area was used as a reference site. Readings from all sites were taken before the application of the irritant, and 24 h after its removal. After the last reading, a 3-mm punch biopsy was taken from each test site for histological examination. The results obtained from electrical impedance measurements at five different skin depths were correlated with those obtained from histological examination, visual scoring and transepidermal water loss (TEWL). For all of the methods used the responses were proportional to the concentration of the irritant. Statistically significant changes of electrical impedance were found for all depths and concentrations, except for 0.1% SLS at the most superficial depth. The histological changes were focused in the epidermis, and mainly consisted of oedema. Alterations in the thickness of the epidermis due to oedema were used as a quantitative parameter for correlation with the assessment of irritation using the electrical impedance technique. For the detection of irritant reactions, TEWL and electrical impedance are more sensitive than visual scoring, and selection of the optimum depth penetration further increases the sensitivity of the electrical impedance measurement. PMID- 7772477 TI - Defective in vivo expression and apparently normal in vitro expression of a newly identified 105-kDa lower lamina lucida protein in dystrophic epidermolysis bullosa. AB - We have previously identified a novel 105-kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune-mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non-lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western-blotted proteins revealed that a comigrating 105-kDa protein is present in both cytosol extracts (n = 6) and conditioned media (n = 3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defective in vivo expression of this novel 105-kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105-kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772478 TI - Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. AB - Basal cell carcinoma (BCC) is typically a slow-growing malignant tumour, composed of cells similar to those in the basal area of the epidermis. We investigated the expression of bcl-2 (B-cell leukaemia/lymphoma-2) in BCC, and also in squamous cell carcinoma (SCC) of the skin. The proto-oncogene bcl-2 encodes a protein which inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but not in the suprabasal cell layers. Immunohistochemical localization using a monoclonal anti-Bcl-2 antibody revealed bcl-2 expression in all the BCCs (15 patients). SCCs did not express bcl-2 (five patients). The positive Bcl-2 staining of BCC tumour cells supports the hypothesis that BCCs originate from the basal layer of the epidermis. The bcl-2 expression of BCC tumour cells also suggests a neoplastic transformation caused by extended cell survival rather than increased cell proliferation. This type of neoplastic growth is possibly associated with less aggressive tumour behaviour. PMID- 7772479 TI - Soluble E-cadherin: a novel cutaneous disease marker. AB - E-cadherin is a major homophilic cell-cell adhesion molecule of the skin. There are two forms of E-cadherin--membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E-cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E-cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E-cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell-surface molecules in the epidermis. PMID- 7772480 TI - The localization of the target antigens and antibodies in linear IgA disease is heterogeneous, and dependent on the methods used. AB - Fifty-nine patients with linear IgA disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772481 TI - Prevalence of dermatophyte onychomycosis in Spain: a cross-sectional study. AB - To evaluate the prevalence of dermatophyte onychomycosis in Spain, a cross sectional study was conducted between 1992 and 1993. A total of 10,007 subjects over the age of 15 years were interviewed (using the computer-assisted telephone interview system), completed a directed questionnaire, and reviewed a series of photographs of diverse nail disorders. The period prevalence of onychomycosis was 2.6% and the point prevalence 1.7%. The prevalence of onychomycosis was higher in women (1.8%) than in men (0.8%). Age group distribution showed a higher onychomycosis prevalence (1.2%) in the oldest age group (> 55 years). With regard to localization, the prevalence of toenail onychomycosis was higher than that of fingernail onychomycosis and of concurrent infection in both sites. The results of this study suggest that 802,893 inhabitants of Spain have, or have previously suffered from dermatophyte onychomycosis. Only 38.6% have sought medical advice, and only 14% of those who did so consulted a dermatologist. PMID- 7772482 TI - The effects of topical indomethacin and clobetasol propionate on post-cryotherapy inflammation. AB - The effects of topical indomethacin and clobetasol propionate on erythema and oedema following low-dose cryotherapy to normal skin were examined using a single blind technique. Both agents significantly reduced erythema, but neither had a significant effect on oedema. A further, controlled, double-blind study comparing topical indomethacin and inert gel base was performed after cryotherapy to hand warts. In this study, topical indomethacin had no significant effect on post cryotherapy oedema, erythema, pain or blister formation 48 and 96 h after treatment. Both potent topical steroids and cyclo-oxygenase inhibitors reduce erythema after low-dose cryotherapy. In clinical practice, there is no evidence that topical indomethacin significantly inhibits the inflammatory response to cryotherapy. PMID- 7772483 TI - Reactions to other corticosteroids in patients with allergic contact dermatitis from hydrocortisone. AB - It has been proposed that corticosteroid cross-reactions occur more frequently within structurally well-defined groups. To test this hypothesis we have compared the patch-test reactions to other corticosteroids in 96 patients allergic to hydrocortisone. We found that our data did not agree with the previously proposed classification. The presence of a substitution at the C6 or C9 position was the most important factor in determining whether a patient would be allergic to another corticosteroid. This information should facilitate the choice of an alternative corticosteroid in patients allergic to hydrocortisone, if facilities for patch testing to other corticosteroids are not available. PMID- 7772484 TI - Prevalence of atopic dermatitis in Leicester: a study of methodology and examination of possible ethnic variation. AB - A study was undertaken to investigate and compare various methods of estimating the prevalence of atopic dermatitis (AD), and to investigate a possible ethnic difference in our local community. Preschool children attending routine child health surveillance clinics and Social Services day nurseries were examined by a trained observer, and their parents were interviewed. In addition, general practice records from a health centre were scrutinized. Three hundred and twenty two children aged 1-4 years were examined, and the point prevalence of AD was 14% [95% confidence interval (CI) 10-18]. There was no apparent ethnic difference in prevalence. Twenty-seven per cent (95% CI 22-32) of parents reported that their children had suffered from 'eczema' at some time. General practitioners' records contained a diagnosis of 'eczema' in 32% (95% CI 28-36) of 446 children aged 1-4 years. It is clear that methodology must be carefully standardized if comparisons are to be made between different studies. Accurate estimations of the prevalence of AD can probably only be obtained by examination of a population sample by a trained observer. However, the estimates obtained in this study are high, and would tend to support existing evidence that the prevalence of AD is rising. PMID- 7772485 TI - Hypnotherapy as a treatment for atopic dermatitis in adults and children. AB - Eighteen adults with extensive atopic dermatitis, resistant to conventional treatment, were treated by hypnotherapy, with statistically significant benefit (P < 0.01) measured both subjectively and objectively, which was maintained at up to 2 years where results were available. Twenty children with severe, resistant atopic dermatitis were treated by hypnosis. All but one showed immediate improvement, which was maintained at the following two clinic appointments. In 12 children, replies to a questionnaire at up to 18 months after treatment, showed that 10 had maintained improvement in itching and scratching, nine in sleep disturbance, and seven maintained improvement in itching and scratching, nine in sleep disturbance, and seven maintained improvement in mood. PMID- 7772486 TI - Minimizing cicatricial pemphigoid orodynia with minocycline. AB - Cicatricial pemphigoid is a rare autoimmune blistering disease of the elderly. It predominantly affects the mucosae, causing pain and scarring. the target antigen is within the lamina lucida of the basement membrane zone. Potential complications of systemic steroid and other immunosuppressive therapy have prompted trials of other means of treatment. We describe a series of seven patients treated with minocycline, six of whom derived sustained alleviation of orodynia. Four patients developed hyperpigmentation, and two complained of gastrointestinal discomfort which necessitated cessation of minocycline. Complete steroid withdrawal was achieved in two cases. Neither the disease progression nor the response to treatment was influenced by the immunoglobulin isotype or titre. The role of minocycline as a useful adjunct to therapy is discussed. PMID- 7772488 TI - Nodular prurigo responds to cyclosporin. AB - Nodular prurigo is a distressing disease which is difficult to treat. Two patients with severe nodular prurigo were treated with cyclosporin for periods of 36 and 24 weeks, respectively, using doses of 3-4.5 mg/kg per day. In both cases there was a reduction in the severity of pruritus after 2 weeks of treatment. In one patient there was a considerable, although incomplete response, and in the other almost complete resolution of the disease was achieved. The improvement was maintained throughout the treatment period, and the drug was generally well tolerated, although in one patient there was a rise in serum creatinine during treatment, which later returned to normal. PMID- 7772487 TI - Topical cyclosporin in oral lichen planus: a controlled, randomized, prospective trial. AB - The published studies of topical cyclosporin (CyA) therapy in chronic oral lichen planus (OLP) have shown conflicting results. We report an investigator-blinded study of 13 patients with OLP, who were randomly assigned to treatment with CyA (500 mg as a swish-and-spit medication for 5 min three times daily) or a corticosteroid oral paste (triamcinolone acetonide). The duration of treatment was 6 weeks. Thereafter, patients on corticosteroid therapy were treated with CyA. Only slight, transient clinical improvement was observed in both groups after 6 weeks of treatment, compared with baseline. No significant differences could be demonstrated between the two groups. CyA therapy following corticosteroid treatment did not produce any further clinical improvement. During follow-up of the disease for up to 1 year after treatment, neither the CyA nor the corticosteroid group exhibited long-term improvement in disease activity. Contradictory results from earlier reports are discussed. PMID- 7772489 TI - Cutaneous infection with Mycobacterium abscessus. AB - Cutaneous infection with rapidly growing mycobacteria is uncommon and diagnosis may be difficult. However, the histopathological features are distinctive and may aid diagnosis. The three pathogenic species, Mycobacterium fortuitum, M. chelonae and M. abscessus, show major differences in their antimicrobial sensitivities, and species identification is therefore important. We describe a case of infection with M. abscessus, and discuss the clinical and pathological features of such infections, and approaches to their treatment. PMID- 7772490 TI - Subcutaneous fat necrosis of the newborn complicating hypothermic cardiac surgery. AB - A newborn male infant developed subcutaneous fat necrosis (SCFN) with extensive calcification, 1 week after hypothermic cardiac surgery. The lesions resolved spontaneously, without sequelae, within 10 weeks. Five cases of SCFN occurring after induced hypothermia, used as an adjuvant in cardiac surgery, have been reported to date in the English literature. Our description of a sixth case re emphasizes hypothermia as one possible cause of SCFN of the newborn. PMID- 7772492 TI - Regressing cutaneous lymphomas of T-cell and B-cell lineage. AB - We report two cases of regressing cutaneous lymphoma. The first case is a CD30 positive T-cell lymphoma with immunogenetic evidence of clonality. The second case is a diffuse large-cell non-Hodgkin's lymphoma of B-cell lineage in which clonality was established by immunogenetic analysis and in situ hybridization for light-chain mRNA. PMID- 7772491 TI - Cutaneous myiasis due to Dermatobia hominis: a report of six cases. AB - We report six cases of Dermatobia hominis myiasis imported into the U.K. from Belize. With increasing international travel, myiasis may be encountered more frequently in countries in which the parasites are not indigenous. The life-cycle of D. hominis is described, and scanning electron micrographs show the detailed appearance of the larva. PMID- 7772493 TI - Hypocomplementaemic urticarial vasculitis, interstitial lung disease and hepatitis C. AB - A 42-year-old man developed persistent urticaria and angio-oedema responsive to systemic steroids. A skin biopsy revealed leucocytoclastic vasculitis. C4 levels were consistently decreased in the setting of a mildly elevated erythrocyte sedimentation rate. Pulmonary function studies revealed a restrictive pattern, and there was eosinophilia in bronchial lavage fluid. Antibody to hepatitis C virus was positive, and there was mild elevation of serum aminotransferase. We believe that this case represents another possible manifestation of immunological disease associated with hepatitis C virus infection. PMID- 7772495 TI - 'Dermatitis neglecta': unwashed dermatosis. PMID- 7772494 TI - Successful treatment of epidermolysis bullosa acquisita using intravenous immunoglobulins. AB - We report a 55-year-old man with severe inflammatory epidermolysis bullosa acquisita. The skin lesions did not respond to various immunosuppressive treatments. The combined administration of prednisone, azathioprine, dapsone and colchicine resulted only in a transient and incomplete resolution of the lesions. The bullae and increased skin fragility were successfully controlled by the addition of high-dose intravenous immunoglobulin therapy. PMID- 7772496 TI - Cyclosporin-induced periungual granulation tissue. PMID- 7772498 TI - Induced bullous pemphigoid. PMID- 7772497 TI - PUVA therapy in disabling pansclerotic morphoea of children. PMID- 7772499 TI - Treatment of Grover's disease with calcipotriol (Dovonex) PMID- 7772500 TI - Dermatophyte infection associated with a local recurrence of bullous pemphigoid. PMID- 7772501 TI - Alopecia areata arising in patients receiving cyclosporin immunosuppression. PMID- 7772502 TI - Contact urticaria to rice. PMID- 7772503 TI - Treatment of inflammatory linear verrucous epidermal naevus with calcipotriol. PMID- 7772504 TI - Quantitative PCR techniques and applications. PMID- 7772505 TI - In vitro inhibition of tumour necrosis factor-alpha and interleukin-6 production by intravenous immunoglobulins. AB - In vitro data about the action of pooled immunoglobulins (Ig) on cytokine (CK) production are controversial. The recent finding of natural antibodies against staphylococcal toxins neutralizing superantigen-induced activation prompted us to design an assay determining their ability to modulate staphylococcal enterotoxin B (SEB) induced CK production (IL-6 and TNF-alpha). Presence of anti-SEB antibodies was demonstrated by a dot-blot assay in the three preparations tested. Preincubation of SEB with pooled Ig prior to addition into the test tube containing PBMCs (neutralizing condition) resulted in a strong inhibition of both TNF-alpha and IL-6 release (TNF alpha: 59 +/- 5% inhibition, P < 0.0001; IL-6: 71 +/- 7% inhibition, P < 0.0001, n = 15). Anti-CD3 MoAb-induced CK production was not modified. During our study it was found that experimental conditions were critical to observe this inhibitory effect. Reversing the previous procedure by adding PBMCs into the test tube containing pooled Ig mixed with SEB resulted in a marked induction of TNF-alpha and IL-6 production. The same observation was made when pooled Ig solely was added (coating condition). F(ab')2 fragments of pooled Ig displayed similar inhibitory capacity when added in neutralizing condition, indicating that the mechanism involved was not Fc dependent. The fragments lost the activating properties of intact Ig when incubated in coating condition, showing that Fc receptor activation occurs in this setting. The present work demonstrates that inhibition of SEB-induced CKs release by pooled Ig can be achieved by SEB neutralization, provided that the experimental conditions avoid activation through the Fc receptor. It can be assumed that similar mechanisms take place in some clinical conditions during which pooled Ig are infused. PMID- 7772506 TI - B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment. AB - Human long-term bone marrow cultures (HLTBMCs) are a valuable in vitro model for studying the role of the haemopoietic microenvironment. Here we report the spontaneous appearance of EBV-positive B cells in 6/40 HLTBMCs from patients with various haematological diseases after 3-5 months of culture. After subcultivation of these cells, a novel type of cell line could be characterized, which displayed surface markers and morphological features typical for EBV transformed B-cell lines. As the deproteinized and ultrafiltrated culture supernatants of these cell lines were found to contain an agent with stroma toxic properties, they were termed SSB lines (stroma-toxic-agent-secreting B-cell lines). This agent also exhibited a colony-inhibitory activity on in vitro myelopoiesis and erythropoiesis. These properties are typical for the two polyamines spermine and spermidine which were detected at elevated levels in the culture supernatants of SSB lines. The hypothesis that latent presence of EBV in bone marrow may induce an increased synthesis of spermine and spermidine, which are known to be associated with malignant haematological diseases and bone marrow aplasia, is discussed. PMID- 7772507 TI - Potentiation of lysis of leukaemia cells by a bispecific antibody to CD33 and CD16 (Fc gamma RIII) expressed by human natural killer (NK) cells. AB - Bispecific antibodies recognizing tumour-associated antigens and trigger molecules expressed on immune effector cells have been shown to redirect cytotoxicity of several types of peripheral blood cells against relevant tumour targets. Among various effector cells, natural killer (NK) cells appear to play a role in defence against leukaemia. Here we report the successful chemical conjugation of monoclonal antibodies to CD33 and CD16 to create a bispecific antibody (BsAb 251 x 3G8). This bispecific antibody is capable of augmenting the killing of otherwise resistant leukaemia cells by peripheral blood lymphocytes (PBL), purified resting NK (R-NK) cells, and activated NK (A-NK) cells. BsAb 251 x 3G8 may play a role in the therapy of acute myeloid leukaemia (AML) through redirecting the cytotoxic activity of endogenous or adoptively transferred NK cells. PMID- 7772508 TI - Soluble tumour necrosis factor receptors, tumour necrosis factor and interleukin 6 in serum in granulocytopenic patients with fever. AB - Serum levels of TNF, IL-6 and soluble TNF receptors p55 and p75 (sTNFR-p55 and sTNFR-p75) were examined in 14 patients with acute myeloid leukaemia during 43 courses of chemotherapy. The patients experienced 30 episodes of fever which occurred during granulocytopenia (defined as granulocyte counts < 0.2 x 10(9)/l) and six fever episodes when granulocyte counts were > 1.0 x 10(9)/l. Febrile episodes were classified as microbiologically defined infection, clinically defined infection, and unexplained fever. Levels of bioactive IL-6 and immunoreactive TNF increased in response to fever during granulocytopenia, whereas bioactive TNF was not detected in any sample in this study. During granulocytopenia, both sTNFR rose significantly in microbiologically defined infection (P < 0.01 for sTNFR-p55 and P < 0.05 for sTNFR-p75), but not in the other two categories. The ratio of sTNFR-p55 to sTNFR-p75 was higher during febrile periods in granulocytopenia than in a non-granulocytopenic situation with granulocyte counts > 1.0 x 10(9)/l (P < 0.01). We conclude that granulocytopenia affects release of the two sTNFR differently during febrile periods, and that release of sTNFR-p75 in response to fever is reduced during granulocytopenia, suggesting a role for the granulocytes in systemic release of sTNFR-p75. PMID- 7772509 TI - Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation. AB - Cord blood has been used successfully for stem cell transplantation in several haematological conditions: Fanconi's anaemia, leukaemia and Wiskott-Aldrich syndrome. On account of the low incidence of GVHD observed following cord blood transplantation, it has been suggested that cord blood be used for HLA-matched, or perhaps one or two antigens mismatched, and unrelated stem cell transplantation. Based on an extensive immunophenotype-functional correlation, we determined that cord blood contains mainly immature unprimed T lymphocytes that are predominantly suppressor cells. Recent findings suggest that dysregulated production of cytokines (IL-1, IL-2, TNF alpha) plays a role in GVHD. We showed that T cells in cord blood express receptors for IL-2, TNF alpha, but no receptors for IL-1. Similarly, NK cells, one of the effector cells of GVHD, express receptors for TNF alpha and gamma IFN but do not express receptors for IL 1, nor IL-2R alpha-chain (CD25) although IL-2R beta-chain is expressed. The potential for activation of T lymphocytes and NK cells therefore exists in the context of bone marrow transplantation. However, the high number of suppressor cells in cord blood most likely modulate the activation of lymphocytes and NK cells thereby minimizing GVHD. PMID- 7772510 TI - Flow cytometry analysis of dual red blood cell populations after bone marrow transplantation. AB - Flow cytometry represents an alternative method to agglutination assays for the accurate quantification of mixed field populations of erythrocytes observed after bone marrow transplantation. Murine monoclonal antibodies directed against the blood group ABH antigens were selected and processed in order to prepare ready-to use fluorescent reagents. Anti-A (NaM87-1F6; IgG3), anti-B (NaM9-2E11; IgG3) and anti-H (NaM19-7E11; IgM) were purified, labelled with fluorescein isothiocyanate, and used in a direct flow cytometry assay. Anti-A1 (NaM1-1C9; IgG3) was no longer active after FITC-labelling and then was used in an indirect assay. The agglutination was prevented by formaldehyde pretreatment of erythrocytes. Using artificially-made double populations of erythrocytes, measured values with mixtures of 1-100% of cells were very closely related to expected values, showing both the sensitivity and the accuracy of the method. From careful investigation of a series of bone-marrow transplanted patients, we conclude that engraftments could be demonstrated earlier by flow cytometry than by agglutination, because minor populations (1-10%) of cells could be determined accurately only with labelled reagents. In addition, the disappearance of the donor cells on a long term follow-up of patients enabled an earlier detection of graft failure in one case. The proposed method provides appreciable help to follow engraftment in patients and may have more general applications for the study of other haemopoietic chimaeras. PMID- 7772511 TI - Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology. AB - Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason, the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established. PMID- 7772512 TI - Needle liver biopsy in thalassaemia: analyses of diagnostic accuracy and safety in 1184 consecutive biopsies. AB - We report the reliability and safety of percutaneous liver biopsy in the evaluation of hepatic iron loading and histology in patients with homozygous beta thalassaemia prior to and in serial biopsies following allogeneic bone marrow transplantation for this disorder. 501 thalassaemic patients aged 11 +/- 4.5 years (range 1-32 years) underwent 1184 consecutive percutaneous liver biopsies without ultrasound guidance. Overall, 81% of biopsies were evaluable for histological examination and grading of iron. The adequacy of liver biopsy specimens increased with patient age: evaluable specimens were obtained in 73% of patients < 5 years of age and in 86% of samples in patients aged > 15 years. The degree of iron overload and fibrosis in each biopsy was reported separately by at least two pathologists who did not know the clinical status of each patient. In 103 biopsies, iron grade by light microscopy corresponded to an iron concentration varying between a mean of 32.46 +/- 14 mumol/g dry weight liver tissue for iron stores graded by light microscopy as absent to 417.6 +/- 150 mumol/g dry weight liver tissue for stores graded as severe. The fibrosis score of multiple samples of liver obtained at autopsy within 100 d of the percutaneous biopsy in 41 patients who died following BMT correlated perfectly with that of the first sample in > 60% biopsies; in most of the discordant cases fibrosis had been underestimated in the percutaneous biopsy. Liver biopsy demonstrated evidence of chronic hepatitis in 30% of patients with normal transaminase and in 57% of patients with transaminase within twice the normal range. Liver biopsy was complicated in six patients (0.5%) by haemoperitoneum, periocholecystic haematoma, kidney haematoma, or bile peritonitis; no complication was fatal. These data demonstrate that percutaneous liver biopsy provides reliable information regarding liver iron and histology in homozygous beta-thalassaemia with an extremely low risk of complications. PMID- 7772513 TI - A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia. AB - A recessively transmitted haemolytic anaemia associated with the lack of protein 4.2 was found in a Tunisian kindred. Trace amounts of this protein (72 kD component) became visible using high-sensitivity Western blots. Band 3 and ankyrin genes were excluded as candidate genes by linkage studies, and nucleotide sequencing of band 3 cytoplasmic domain cDNA revealed no alteration. In contrast, protein 4.2 gene contained in the homozygous state a mutation at position 310: CGA-->CAA (Arg-->Gln). This mutation defining allele 4.2 Tozeur was co-inherited with the disease. The mRNA encoding the variant protein was normal in size and approximately normal in amount. Recombinant protein 4.2 Tozeur bound normally to red cell IOVs but disclosed an increased susceptibility to proteolysis in vitro. We infer that the nearly total absence of protein 4.2 in the patients results from imbalance between destruction and synthesis of mutated protein 4.2 prior to its binding to the membrane. PMID- 7772514 TI - High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study. AB - We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m2 over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGy x 2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8.5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. Of the 46 patients who underwent AlloBMT, 33 had isolated or combined marrow relapse and 13 isolated extramedullary relapse. Of the 29 patients given ABMT, 23 had preBMT isolated or combined marrow relapse and six isolated extramedullary relapse. 44/75 patients are alive and in CR at a median follow-up of 35 months (range 10 90 months). Seven children given AlloBMT (15.8%) and two given ABMT (7%) died from transplant-related causes. No major early organ toxicity, including vincristine-related toxicity, was recorded. The overall 3-year EFS estimate (95% CL) was 53.8% (42-66%): in particular, 58.2% (40-76%) for AlloBMT and 27.6% (9 46%) for ABMT patients who experienced a marrow relapse before transplant. The overall 3-year relapse rate estimate (95% CL) was 39.2% (27-51%): in particular, 30.1% (12-49%) in the AlloBMT group and 72% (54-91%) in the ABMT group (P < 0.01) who presented a preBMT isolated or combined marrow relapse. We conclude that the conditioning regimen with high-dose vincristine combined with cyclophosphamide and F-TBI is feasible and promising, although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies. PMID- 7772515 TI - Over-expression of cyclin D1 in chronic B-cell malignancies with abnormality of chromosome 11q13. AB - Accurate identification of B-cell chronic malignancies is sometimes uncertain, despite careful cytologic and immunophenotypic evaluation. Cytogenetics and molecular biology studies may therefore prove useful, because some of these disorders are associated with non-random abnormalities, such as the t(11;14)(q13;q32) translocation and bcl-1 rearrangement mainly observed in mantle cell lymphoma (MCL). We studied the expression of cyclin D1 in malignant lymphoid cells from the peripheral blood of 32 patients with various B-cell chronic lymphoproliferative disorders, using Northern blot (NB) and RNA in situ hybridization (ISH). Cytogenetic analysis was informative in 18 cases, and most of the missing karyotype data were from typical B-CLL cases where a t(11;14) is unlikely to be found. Over-expression of cyclin D1 mRNA was observed by both NB and ISH in four samples (MCL; two cases; lymphoplasmacytic lymphoma: one case, unclassified B-cell chronic disorder: one case). In each of these cases there was an abnormality of chromosome 11q13, either a t(11;14)(q13;q32) translocation (three cases) or a del(11)(q13) without evidence of chromosome 14 involvement (one case). Cytogenetic and gene rearrangement studies are not available in all institutions and have some technical pitfalls. Because of its close association with bcl-1 rearrangement and/or t(11;14), the demonstration of cyclin D1 mRNA over-expression either by NB, or, more conveniently, by ISH, may represent additional information which could be of help for the identification of B-cell malignancies. PMID- 7772516 TI - Establishment of a myeloid leukaemic cell line (SKNO-1) from a patient with t(8;21) who acquired monosomy 17 during disease progression. AB - A novel cell line SKNO-1 was established from the bone marrow cells of a 22-year old male suffering from acute myeloblastic leukaemia (AML) M2 with t(8;21) whose disease became resistant to chemotherapy after acquisition of 17 monosomy. SKNO-1 has been maintained for more than 36 months as a granulocyte-macrophage colony stimulating factor (GM-CSF) dependent line. Morphologically, SKNO-1 cells were myeloblasts somewhat matured. The cells grow in suspension with a doubling time of 48-72 h. The survival and growth of SKNO-1 cells was absolutely dependent on granulocyte-macrophage colony stimulating factor (GM-CSF). SKNO-1 cells possessed t(8;21) and monosomy 17 which were observed in original leukaemic cells. We confirmed that the AML1 gene, located on chromosome 21, was rearranged and the AML1-MTG8 fusion transcript was expressed in SKNO-1 cells. Over-expression and mutation of the p53 gene were also detected in SKNO-1. It is likely that alterations of AML1 or MTG8 gene and p53 gene contribute to a disease progression in this case. Since t(8;21) translocation is a common chromosome abnormality in AML, and inactivation of the p53 gene may play a crucial role in disease progression in AML, SKNO-1 would be a useful tool for analysing the molecular mechanisms in myeloid leukaemogenesis. PMID- 7772517 TI - Cobalamin forms and analogues in plasma and myeloid cells during chronic myelogenous leukaemia related to clinical condition. AB - Plasma and buffy coat specimens of CML patients with untreated disease, in chronic and accelerated phase, and in overt blastic crises were analysed for the cobalamin patterns using non-polar extraction, thin-layer chromatography and bioautography. Splenic tissue specimens from four splenectomized patients in accelerated phase were analysed similarly. Cellular extracts were separated into two compartments by adsorption to haptocorrin antibodies. Plasma concentrations of all cobalamin forms were increased in CML. The proportion of methylcobalamin was significantly lower than in a reference population, and a low plasma proportion of methylcobalamin was associated with a poor prognosis. Buffy coat cells and splenic tissue had a higher proportion of 5'-deoxyadenosylcobalamin and a lower proportion of methylcobalamin than plasma; still, there was relatively more methylcobalamin than in normal tissue. The haptocorrin-bound compartment differed from the non-haptocorrin compartment in untreated or chronic phase patients by binding less methylcobalamin. An estimate of cobalamin analogues in plasma was achieved by comparing two different isotope dilution assays employing a cobalamin-specific binder, intrinsic factor, and a nonspecific binder, hog non intrinsic factor. Values for total cobalamin and analogues were increased to the same degree in CML plasma. PMID- 7772518 TI - Bone marrow pathology in relapsing polychondritis: high frequency of myelodysplastic syndromes. AB - Haemopathologic changes were studied in 19 patients (13 male, six female, age 33 85 years, mean 56 years) with relapsing polychondritis (RP). Anaemia was found in eight, thrombocytopenia in two and splenomegaly in three patients. A total of 17 bone marrow biopsies were obtained from seven individuals. Bone marrow evaluation revealed myelodysplastic syndromes (MDS) with marked trilineage hyperplasia and dysplasia in three cases. Since an excess of myeloblasts or an increase of CD34 positive progenitor cells was not seen, the disorders were designated as 'refractory anaemia' or with regard to the dysplastic megakaryopoiesis 'MDS, unclassifiable'. Two of the three patients died after 10 and 55 months of follow up due to infectious complications. In a further patient, bone marrow analysis repeatedly showed an unexplained granulopoietic hyperplasia, which, however, was not dysplastic enough to allow a diagnosis of MDS. The remaining patients had clearly reactive changes. Our findings support the notion that RP is a heterogenous disorder and suggest that RP may at times represent a paraneoplastic phenomenon of an underlying MDS. Since HLA typing revealed a significantly increased frequency of the antigen DR4 (10/17 patients positive = 59%), we hypothesize that immunological imbalances due to the MDS in conjunction with a specific immunogenetic background may play key roles in the pathogenesis of RP in these patients. PMID- 7772519 TI - The use of r-HuEpo in the treatment of anaemia related to myelodysplasia (MDS). AB - One hundred and sixteen (116) anaemic patients with myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (r-HuEpo) in an open label, multicentre, compassionate treatment trial; 100 patients received therapy for > or = 4 weeks and were evaluable for efficacy. The distribution of FAB subtypes was: 44 RA, 40 RARS, eight RAEB, two RAEB-t, one CMML, and five not specified. Mean baseline haematocrit was 24.5%, and the mean prestudy transfusion requirement in the 12 weeks immediately prior to study entry was 6.5 units. r HuEpo treatment was initiated at a dose of 150 U/kg three times weekly, with dose escalations of 50 U/kg monthly (up to 300 U/kg 3x/week) permitted if the haematocrit failed to rise. Response to therapy was defined as either an increase in haematocrit of > or = 6 percentage points over baseline, unrelated to transfusion, or a > or = 50% decrease in transfusion requirement in the last 3 months of study treatment, compared to the baseline period (12 weeks). By these criteria, 28% (28/100) of patients responded to r-HuEpo treatment. Overall, 86% (24/28) of patients responding to therapy had baseline Epo levels < or = 100 mU/ml. Response rates by FAB subtype were: RA 39% (17/44), RARS 17.5% (7/40) and RAEB 12.5% (1/8). Additionally, a 54% (15/28) response rate was seen in RA patients with baseline Epo levels < or = 100 mU/ml. Responses to therapy were durable and generally occurred at r-HuEpo doses of 150-200 U/kg t.i.w. There were no reports of thrombosis, seizures or therapy-related hypertension. The data show that patients with MDS, especially those with the RA and RARS subtypes, can benefit from treatment with r-HuEpo. Those patients with baseline Epo levels < or = 100 mU/ml were most likely to respond to therapy. PMID- 7772520 TI - Clonal analysis of peripheral blood and haemopoietic colonies in patients with aplastic anaemia and refractory anaemia using the polymorphic short tandem repeat on the human androgen-receptor (HUMARA) gene. AB - The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen-receptor gene (HUMARA). Peripheral blood samples were obtained from 12 female patients, six with aplastic anaemia (AA) and six with refractory anaemia (RA). Peripheral blood was fractionated into granulocytes, lymphocytes, T lymphocytes and B lymphocytes. DNA was extracted from each fraction. Bone marrow samples were obtained from seven female patients (three with AA and four with RA). Sorted CD34 positive cells were cultured in a semisolid culture system. DNA was extracted from a 14-day haemopoietic colony. The clonal pattern was assessed using HUMARA gene STR polymorphism and the differential methylation pattern of nearby cytosine residues by PCR methods. Four of six (67%) AA and two of six (33%) RA patients had a monoclonal proliferating pattern in their granulocytes. The ratio of the numbers of minority colonies per majority colonies (m/M ratio) was examined for seven patients (three AA and four RA). In patients who had a clonal haemopoietic pattern in peripheral WBC the ratio was under 0.4 but not zero. In contrast, patients exhibiting a polyclonal pattern had an m/M ratio above 0.8. We concluded that some normal or heterogenous haemopoietic clones, not only MDS but also AA, may remain in the bone marrow, although almost all colonies were derived from a single pathogenic clone when the clonality pattern exhibited monoclonality in peripheral blood analysis. PMID- 7772521 TI - A specific allele of the histidine-rich glycoprotein (HRG) locus is linked with elevated plasma levels of HRG in a Dutch family with thrombosis. AB - Recent studies describe families with both elevated plasma HRG levels and thrombosis. In order to study the possibility that allelic variants of the HRG locus are associated with differences in HRG level, we studied linkage between HRG levels and a dinucleotide repeat polymorphism in a Dutch family which was selected on the presence of both thrombosis and elevated plasma HRG levels. No other known risk factors from thrombosis were found in this family. Linkage was calculated between the dinucleotide repeat and the HRG level considering the HRG level as a quantitative phenotype assuming a population prevalence of elevated HRG of 5%. Two classes of HRG levels were defined by a mean and a variance: one class with normal HRG levels and a second class with high HRG levels. Using a mean HRG level of 99% for individuals with a normal HRG level and 145% for individuals with high HRG, a maximum lod score of 4.17 (odds in favour of linkage of 22,000:1) was found at a recombination fraction of 0, indicating linkage. Considering the pedigree, an association was found between the presence of a specific allele (no. 6) of the dinucleotide repeat polymorphism and plasma HRG levels. Family members carrying allele 6 were found to have higher HRG plasma levels compared with family members lacking allele 6 (149% v 109% respectively). We conclude that in this family, linkage is found between the HRG locus and the HRG level, and that a HRG gene coupled to allele 6 of the dinucleotide polymorphism is associated with elevated plasma HRG levels. No evidence was found for a causal relationship between elevated plasma HRG levels and thrombosis in this family. PMID- 7772522 TI - Platelet activation induced by a murine monoclonal antibody directed against a novel tetra-span antigen. AB - MAb 14A2.H1 identifies a novel low-abundance platelet surface antigen, PETA-3, which is a member of the tetra-span (TM4) family. This MAb brings about platelet aggregation and mediator release, which is completely inhibitable by prostaglandin E1, and partially inhibitable by aspirin and ketanserin. Platelet activation by MAb 14A2.H1 is dependent on interaction with both the platelet Fc receptor, Fc gamma RII, and the specific antigen as it was prevented by either a blocking MAb to Fc gamma RII (IV.3) or F(ab')2 fragments of 14A2.H1. The extent of platelet activation by the antibody varied considerably between donors, and is believed to reflect the polymorphism of Fc gamma RII. Subaggregating concentrations of 14A2.H1 synergized with other platelet agonists, ADP, adrenaline, collagen and serotonin, indicating signalling via a pathway distinct from these activators. Synergy was also blocked by MAb IV.3, or F(ab')2 fragments of 14A2.H1. The similar low copy number of PETA-3 and Fc gamma RII in the platelet membrane (approximately 1000/platelet), together with the dependence on Fc gamma RII for activation by MAb 14A2.H1, suggests that PETA-3 may be a component of the Fc gamma RII signal transducing complex in platelets. PMID- 7772523 TI - Impaired high-shear-stress-induced platelet aggregation in patients with chronic renal failure undergoing haemodialysis. AB - We investigated shear-induced platelet aggregation (SIPA) in 30 patients with chronic renal failure (CRF) undergoing haemodialysis. 26 patients showed a significant decrease in SIPA at high shear stress but no change in SIPA at low shear stress. The former reaction reflects the interaction between plasma von Willebrand factor (vWF) and its platelet receptors, glycoprotein (GP) Ib-IX and IIb/IIIa complex, whereas the latter is assumed to involve the binding of plasma fibrinogen to GP IIb/IIIa complex. These SIPA profiles in CRF patients after haemodialysis showed almost no change compared to those before haemodialysis. The ratio of ristocetin cofactor/vWF antigen in plasma was slightly lower in CRF patients than in controls (P < 0.01). However, the level of GPIb antigen in the platelets of these patients was significantly reduced (42.1 +/- 20.3% of normal platelets), with partial destruction of GPIb antigen. The number of vWF receptors on the GPIb molecule was quantitated using the GPIb-binding protein alboaggregin B (AL-B), purified from the snake venom of Trimeresurus albolabris. AL-B bound to GPIb at a total of 48,760 +/- 9944 molecules per normal platelet and a Kd of 85.44 +/- 15.70 nM at saturation. In contrast, binding in CRF platelets was 22,980 +/- 6395 molecules per platelet and Kd was 50.08 +/- 13.83 nM. Taking these results together, we conclude that the impaired SIPA found in CRF patients is due to both abnormalities in plasma vWF and in its platelet GPIb receptor. PMID- 7772524 TI - Desferrioxamine therapy accelerates clearance of iron deposits after bone marrow transplantation for thalassaemia. AB - We treated 18 heavily iron-loaded patients who had become ex-thalassaemics after bone marrow transplantation with subcutaneous desferrioxamine therapy for 5-20 months. As determined using serum ferritin concentration, transferrin saturation and stainable liver iron obtained in follow-up biopsies, marked decreases in body iron stores were observed with this regimen. Moreover, the liver function tests demonstrate a trend to normalization in all cases. Local skin reactions to desferrioxamine were the only toxicities observed. We conclude that pharmacological iron chelation is a safe and effective therapy in the reduction of iron deposits in this clinical situation; it therefore represents a valid alternative to phlebotomy in selected patients. PMID- 7772525 TI - Assessment of intestinal blood-flux by laser Doppler fluxmetry in mice with altered intestinal iron absorption. AB - Laser Doppler fluxmetry (LDF) has been used to assess mucosal blood-flux in the intestine of normal CD1 mice and groups of animals with altered iron metabolism (i.e. iron-deficient, hypoxic and hypotransferrinaemic [hpx/hpx]). All experimental animals showed a 2-3-fold increase in duodenal iron absorption, mainly due to changes in the 'mucosal transfer' phase. However, only the hypoxic mice exhibited any increases in duodenal blood-flux. In the hpx/hpx group, blood flux was maintained at control levels despite the anaemia and without any significant alterations in red blood cell velocity. Moreover, these two groups demonstrated a further capacity to increase blood-flux above basal levels during onset of acute hypoxia (inhalation of 10% O2). Changes in duodenal blood-flux were apparent on both the mucosal and serosal surfaces, suggesting that the LDF signal reflects flux throughout the thickness of the mouse intestine. Iron absorption is likely to be more related to plasma flux changes than to blood-flux changes. Deduction of plasma flux changes from blood-flux changes is complicated by vasodilation effects on capillary haematocrits. It is clear from the data, however, that plasma flux changes do not parallel changes in iron absorption in the experimental models. The lack of correlation between the duodenal blood-flux and iron absorption values in the experimental models argues against the possible involvement of blood-flux in the control of duodenal iron absorption. PMID- 7772526 TI - Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients. AB - The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens. PMID- 7772527 TI - t(8;21) myelodysplasia, an early presentation of M2 AML. AB - The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryocytes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the third had a variant t(8;21) translocation. We discuss the significance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients. PMID- 7772528 TI - Factor V inhibitor associated with Sjogren's syndrome. AB - We report an unusual case of a 74-year-old male who developed a serum autoantibody reactive with human coagulation factor V (FV) in an activated form, as demonstrated by coagulation studies and immunoblotting analysis. Despite marked prolongation of a prothrombin time and an activated partial thromboplastin time in this patient, the inhibitor was not associated with clinical bleeding but with multiple cerebral infarctions. The patient had suffered from Sjogren's syndrome with polyclonal hypergammaglobulinaemia. The patient's purified IgG, an immediately acting inhibitor to FV, reacted with a light chain of thrombin activated FV (FVa) and inhibited the procoagulant activity of FVa without affecting the cleavage of FVa by activated protein C. The FV inhibitor may arise from activation of FV with consequent exposure of neoantigen during the activation of coagulation cascade in the patient with an autoimmune disorder for the background. PMID- 7772529 TI - Familial thrombocytosis. AB - Four cases of thrombocytosis in three successive generations of a family are described. High peripheral platelet count was found incidentally in the proband with cutaneous malignant lymphoma. Bone marrow examination showed megakaryocytic hyperplasia. Neither Philadelphia chromosome nor chimaeric bcr/abl junction was detected in marrow cells. In this family, thrombocytosis was thought to be transmitted by an autosomal dominant mode of inheritance. PMID- 7772530 TI - A possible anti-emetic role for sodium valproate in cytotoxic chemotherapy. AB - We report two patients with acute leukaemia who received emetogenic cytotoxic drugs and were on therapeutic doses of sodium valproate for epilepsy. Neither patient reported significant nausea nor vomited at any time during the chemotherapy, at times requiring no anti-emetic treatment whatsoever. We suggest that this absence of nausea was due to an anti-emetic effect of sodium valproate. PMID- 7772532 TI - The incidence of factor VIII inhibitors in the United Kingdom, 1990-93. Inhibitor Working Party. United Kingdom Haemophilia Centre Directors Organization. AB - Reports of all the factor VIII inhibitors arising in the United Kingdom in patients with haemophilia A during the years 1990-93 have been collated by the United Kingdom Haemophilia Centre Directors Organization. 32 new inhibitors were reported during this period, giving an average incidence of new inhibitors of 1.5 per 1000 patients registered per year. Although most occurred in patients with severe haemophilia under the age of 10, 29% occurred in patients whose VIIIC was > 3 iu/dl, and 38% in patients over the age of 10 years. The incidence of inhibitors rose during the study period, but this change was not statistically significant. PMID- 7772531 TI - Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma. AB - CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35) ALCL cases based on a long-range PCR of genomic DNA. The rapidity and robustness of this method may have diagnostic applications for ALCL. PMID- 7772533 TI - Correction of anaemia and thrombocytopenia in a case of adult type I osteopetrosis with recombinant human erythropoietin (rHuEPO). AB - A case of adult osteopetrosis Type I was diagnosed in a 22-year-old female. She presented for investigation of anaemia with 'myelophthisic' characteristics and extramedullary haemopoiesis which was resistant to haematinics, nandrolone and low-dose corticosteroids. She became progressively transfusion-dependent with gradually worsening thrombocytopenia. She was successfully treated with recombinant erythropoietin. Anaemia as well as thrombocytopenia were corrected. There appeared to be a synergistic action of erythropoietin with steroids. PMID- 7772534 TI - Long-term disease-free survival after autologous bone marrow transplantation in a primary plasma cell leukaemia: detection of minimal residual disease in the transplant marrow by third-complementarity-determining region-specific probes. AB - Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell neoplasm. Treatments of PPCL have been most disappointing. A patient with PPCL received high-dose melphalan plus total body irradiation and autologous bone marrow transplantation (ABMT). By using third-complementarity-determining region (CDRIII)-specific probes, minimal residual disease (MRD) was detected in remission marrow, collected 1 month before ABMT. MRD was no longer detected by CDRIII-specific probes 6, 19 and 26 months after transplantation. The patient remained in complete remission up to 59 months after ABMT. PMID- 7772535 TI - AcSDKP serum concentrations vary during chemotherapy in patients with acute myeloid leukaemia. AB - AcSDKP is a physiological negative regulator of cell proliferation in mammals. In Ara-C-treated mice its plasmatic concentrations decrease while the CFU-S start cycling. Infusion of AcSDKP protects these animals from death by blocking the proliferation of primitive haemopoietic cells. We measured AcSDKP serum concentrations in 20 AML patients during the course of high-dose cytoreductive treatment. We observed an early and sharp increase of AcSDKP during the induction treatment in 12 patients, reaching a peak during the initial 3 d of treatment in nine of them. These results are contrary to those observed in mice treated with high doses of Ara-C. They encourage further clinical investigation, and suggest that treatments with synthetic AcSDKP (Seraspenide) will perhaps have to be adjusted to the type of disease and the schedule of chemotherapy in order to optimize its myeloprotective effect. PMID- 7772536 TI - Acute lymphoblastic transformation of essential thrombocythaemia. AB - Essential thrombocythaemia is a myeloproliferative disorder which may transform to acute myeloid leukaemia, especially following therapy with alkylating agents or radioactive phosphorus. We describe the rare occurrence of acute lymphoblastic leukaemia transformation in a patient with known essential thrombocythaemia. PMID- 7772537 TI - Parvovirus B19-associated haemophagocytic syndrome in healthy adults. AB - Between August 1992 and August 1994 we found seven adult patients with haemophagocytic syndrome associated with human parvovirus B19 (HPV) infection. Five of the patients were previously healthy but the other two had underlying immunosuppressive disease; the former five patients recovered spontaneously without any treatment. Eight cases of HPV-associated haemophagocytic syndrome have been reported; six of them were children and the remainder were adults with immunosuppressive disease or haematological disorder. Our study suggests that HPV is not a rare cause of virus-associated haemophagocytic syndrome (VAHS). Moreover, HPV-associated haemophagocytic syndrome could occur more frequently than previously thought, not only in children and adults with underlying disease but also in adults, even in good health. PMID- 7772538 TI - alpha-Interferon therapy for congenital dyserythropoiesis type I. AB - We report the case of a 28-year-old female followed for congenital dyserythropoiesis type I which required repeated transfusions. Alpha-2a interferon treatment was started because of post-transfusion chronic viral hepatitis type C. Following this treatment, haemoglobin level increased and reached normal value during the 24 weeks of interferon treatment. When interferon therapy was stopped, haemoglobin level returned to previous values, requiring more transfusions. Resumption of interferon therapy resulted again in a complete normalization of haemoglobin level. Erythrokinetic studies demonstrated a striking reduction of the ineffective erythropoiesis, and electron microscopy study a reduction in nuclear structure abnormalities. To our knowledge, this is the first report of the efficacy of interferon in congenital dyserythropoiesis. PMID- 7772539 TI - Spectrin Anastasia (alpha I/78): a new spectrin variant (alpha 45 Arg-->Thr) with moderate elliptocytogenic potential. AB - We describe a white Italian kindred in which hereditary elliptocytosis (HE) is associated with abnormal level of alpha I/78 peptide in spectrin digest. Clinical phenotype varied among the family members ranging from asymptomatic to mild haemolytic HE. The original mutation responsible is a G-C substitution of the spectrin alpha-gene: alpha 45 Arg-->Thr (AGG-->ACG). The corresponding spectrin is designated spectrin Anastasia. Utilizing a secondary structure predictive method we suggest that this mutation has a poor capability to induce conformational changes of the tetramerization site and thus shows a moderate elliptocytogenic potential. PMID- 7772540 TI - PCR-monitoring of minimal residual leukaemia after conventional chemotherapy and bone marrow transplantation in BCR-ABL-positive acute lymphoblastic leukaemia. AB - We report the results of consecutive tests in nine BCR-ABL-positive ALL patients by one-step and two-step (nested primer) reverse transcriptase-polymerase chain reaction (RT-PCR). Six patients could be tested in complete haematological remission (CHR). One patient remained one-step positive; four patients became one step negative, but remained two-step positive; only one patient became two-step negative. In five patients the haematological relapse was preceded by one-step positivity by 1.5-5 weeks. In two patients who received autologous BMT in CHR, BCR-ABL was still detectable by two-step PCR, whereas allogeneic BMT was able to transiently reduce BCR-ABL below the two-step detection level. Our results show that one-step combined with two-step RT-PCR analysis gives valuable information about the efficacy of treatment and the dynamics of the leukaemic clone. PMID- 7772541 TI - Is hairy cell leukaemia more common among farmers? PMID- 7772542 TI - Human herpesvirus-6 (HHV-6) in blood donors. PMID- 7772543 TI - Prophylaxis against infections with intravenous immunoglobulins in multiple myeloma. PMID- 7772544 TI - Methods of measurement of Rh haemolytic disease. PMID- 7772545 TI - Spontaneous remission in monosomy 7 myelodysplastic syndrome. PMID- 7772546 TI - Theoretical issues in symmetry perception. PMID- 7772547 TI - Detection of bilateral symmetry using spatial filters. AB - When bilaterally symmetric images are spatially filtered and thresholded, a subset of the resultant 'blobs' cluster around the axis of symmetry. Consequently, a quantitative measure of blob alignment can be used to code the degree of symmetry and to locate the axis of symmetry. Four alternative models were tested to examine which components of this scheme might be involved in human detection of symmetry. Two used a blob-alignment measure, operating on the output of either isotropic or oriented filters. The other two used similar filtering schemes, but measured symmetry by calculating the correlation of one half of the pattern with a reflection of the other. Simulations compared the effect of spatial jitter, proportion of matched to unmatched dots and width or location of embedded symmetrical regions, on models' detection of symmetry. Only the performance of the oriented filter + blob-alignment model was consistent with human performance in all conditions. It is concluded that the degree of feature co-alignment in the output of oriented filters is the cue used by human vision to perform these tasks. The broader computational role that feature alignment detection could play in early vision is discussed, particularly for object detection and image segmentation. In this framework, symmetry is a consequence of a more general-purpose grouping scheme. PMID- 7772548 TI - Modelling symmetry detection with back-propagation networks. AB - This paper reports experimental data and results of network simulations in a project on symmetry detection in small 6 x 6 binary patterns. Patterns were symmetrical about the vertical, horizontal, positive-oblique, or negative-oblique axis, and were viewed on a computer screen. Encouraged to react quickly and accurately, subjects indicated axis of symmetry by pressing one of four designated keys. Detection times and errors were recorded. Back-propagation networks were trained to categorize the patterns on the basis of axis of symmetry, and, by employing cascaded activation functions on their output units, it was possible to compare network performance with subjects' detection times. Best correspondence between simulated and human detection-time functions was observed after the networks had been given significantly more training on patterns symmetrical about the vertical and the horizontal axes. In comparison with no pre-training and pre-training with asymmetric patterns, pre-training networks with sets of single vertical, horizontal, positive-oblique or negative oblique bars speeded subsequent learning of symmetrical patterns. Results are discussed within the context of theories suggesting that faster detection of symmetries about the vertical and horizontal axes may be due to significantly more early experience with stimuli oriented on these axes. PMID- 7772549 TI - A network model for generating differential symmetry axes of shapes via receptive fields. AB - Some symmetries (e.g. bilateral, rotational, translational) only describe quite specialized shapes, but differential symmetry axes (e.g. Blum, J. Theoret. Biol. 38, 205-287, 1973; Brady and Asada, Int. J. Robotics Res. 3, 36-61, 1984) describe more general shapes. Such axes are of interest in part because they form the 'backbone' of generalized cylinder and other shape representations used in shape recognition (e.g. Marr, Vision, W. H. Freeman and Co., NY, 1982; Biederman, Psychol. Rev. 94, 115-147, 1987). However, despite the popularity of these representations as psychological models, algorithms from machine vision for computing them have strong limitations as psychological models. This paper presents two versions of a network model, one of which is more plausible as a psychological model because it derives symmetry axes from the activations of idealized visual receptive fields. PMID- 7772550 TI - Symmetric 3D objects are an easy case for 2D object recognition. AB - According to the 1.5-views theorem (Poggio, Technical Report #9005-03, IRST, Povo, 1990; Ullman and Basri, IEEE Trans. PAMI 13, 992-1006, 1991) recognition of a specific 3D object (defined in terms of pointwise features) from a novel 2D view can be achieved from at least two 2D model views (for each object, for orthographic projection). This note considers how recognition can be achieved from a single 2D model view by exploiting prior knowledge of an object's symmetry. It is proved that, for any bilaterally symmetric 3D object, one non accidental 2D model view is sufficient for recognition since it can be used to generate additional 'virtual' views. It is also proved that, for bilaterally symmetric objects, the correspondence of four points between two views determines the correspondence of all other points. Symmetries of higher order allow the recovery of Euclidean structure from a single 2D view. PMID- 7772551 TI - Continuous symmetry: a model for human figural perception. AB - Symmetry is usually viewed as a discrete feature: an object is either symmetric or non-symmetric. In this presentation, symmetry is treated as a continuous feature and a continuous measure of symmetry (the Symmetry Distance) is defined. This measure can be easily evaluated for any shape or pattern in any dimension. A preliminary study presented here shows that the Symmetry Distance is commensurate with human perceptual experience. Good correlation is found between the continuous symmetry values and the perceived goodness of figures. PMID- 7772552 TI - Mirror symmetry and parallelism: two opposite rules for the identity transform in space perception and their unified treatment by the Great Circle Model. AB - Two opposite rules control the contributions of individual lines to the perceptual processing of two different spatial dimensions of egocentric localization and orientation. For lines restricted to the frontal plane, a tilted line on one side of the median plane induces a rotation of the orientation visually perceived as vertical (VPV) identical to that induced by the same tilt on the other side of the median plane, but the influences exerted on the elevation of visually perceived eye level (VPEL) are mirror symmetric. The rule for VPV fits our intuitions; the rule for VPEL does not. However, the reverse peculiarity holds when the inducing lines are rotated within sagittal planes (pitched): Two parallel, pitched-from-vertical lines on opposite sides of the median plane generate identical effects on VPEL but mirror symmetric effects on VPV. These counterintuitive symmetry reversals are reconciled by the Great Circle Model of spatial orientation (GCM), in which line orientations are represented by the great circle coordinates of their images on a sphere centered at the nodal point of the eye via central projection. PMID- 7772553 TI - The generalized cone in human spatial organization. AB - The generalized cone is one of the newer concepts useful for describing spatial structures, and it has become popular as a volumetric primitive in models of object recognition. Apart from this use of the concept (or perhaps underlying it), the generalized cone can be considered a species of spatial regularity. In the general definition of symmetry as invariance across transformation, the generalized cone is a combination of translation and dilation symmetry. In such symmetry, there is homogeneity both of the slants of edges and surfaces of an object about an axis and the radial positions of these features about the axis. The results of two research projects are reviewed suggesting that the generalized cone is useful in human spatial organization. In the first instance, each of the three simpler regular polyhedra, the Platonic Solids, are easiest to perceive and imaging when they are organized as generalized cones. In the second instance, people imagine simple rotations best when the symmetric space that would be traced by the motion is aligned with salient spatial reference systems. PMID- 7772554 TI - A continuum of non-Gaussian self-similar image ensembles with white power spectra. AB - We introduce a scaling procedure that acts on visual textures to produce new textures having the same resolution, display size, and mean contrast power. We derive the form of the scaling fixed-point textures (image ensembles) resulting from repeated application of this scale transformation to the 'even' texture with an arbitrary amount of sporadic decorrelation. The result is a continuum of scaling fixed-point or 'self-similar' image ensembles, ranging from a strongly non-Gaussian white texture with higher-order spatial correlations at one extreme to Gaussian white noise at the other. The simple construction of a continuum of self-similar ensembles possessing phase correlations provides a tool for investigating human perception of structure in the absence of useful length scales. The fixed-point textures have luminance histogram differences, a direct result of their higher-order spatial properties. This suggests that scaling might afford an extension of our understanding of IID (independent identically distributed) texture discrimination (Chubb et al., J. Opt. Soc. Am. A 11, 2350 2374, 1994) to more general texture discrimination tasks in which spatial correlations play a role. PMID- 7772555 TI - Quantification of local symmetry: application to texture discrimination. AB - Symmetry is one of the most prominent cues in visual perception as well as in computer vision. We have recently presented a Generalized Symmetry Transform that receives as input an edge map, and outputs a symmetry map, where every point marks the intensity and orientation of the local generalized symmetry. In the context of computer vision, this map emphasizes points of high symmetry, which, in turn, are used to detect regions of interest for active vision systems. Many psychophysical experiments in texture discrimination use images that consist of various micro-patterns. Since the Generalized Symmetry Transform captures local spatial relations between image edges, it has been used here to predict human performance in discrimination tasks. Applying the transform to micro-patterns in some well-studied quantitative experiments of human texture discrimination, it is shown that symmetry, as characterized by the present computational scheme, can account for most of them. PMID- 7772556 TI - 1995 Annual Meeting of the American Society of Regional Anesthesia. Orlando, Florida, March 30-April 2, 1995. Abstracts. PMID- 7772557 TI - Galactomannans from Brazilian seeds: characterization of the oligosaccharides produced by mild acid hydrolysis. AB - Galactomannans with Man:Gal ratios ranging from 1.1:1 to 3:1, obtained from the seeds of Mimosa scabrella, Stryphnodendron barbatiman, Schizolobium parahybum and Schizolobium amazonicum, were submitted to mild acid hydrolysis. The products were fractionated by gel permeation chromatography on BioGel P2 yielding fractions with degrees of polymerization (DP) of 1 to 6. Those with DP 2 to 6 from each species were analysed by ion-exchange high-performance liquid chromatography and characterized by 13C- and 1H-nuclear magnetic resonance (NMR) spectroscopy. The distribution of the oligosaccharides of each degree of polymerization was very similar for the products from S. parahybum and S. amazonicum, indicating the same D-galactosyl distribution on the D-mannan backbone, in agreement with the 13C-NMR splitting in the C4 region of the D mannosyl units in the original polymers. The hydrolytic conditions adopted allowed characterization of compounds that are not generally produced by enzymatic treatments. The results show that the structures of the oligosaccharides, even if there is a preferential hydrolysis of Gal-Man linkages, reflect the composition of the parent polymer. PMID- 7772558 TI - Synthesis of chitosan-amino acid conjugates and their use in heavy metal uptake. AB - Chitosan-amino acid conjugates were prepared by coupling amino acid esters to the carboxyl group of glyoxylic acid-substituted chitosan. The removal of heavy metals (Cu, Ni, Co and Mn) was increased by introduction of amino acids to chitosan, especially for Mn. Heavy metals were almost completely removed by chitosan-amino acid conjugates from solutions at an initial concentration of 100 parts per million. PMID- 7772559 TI - Kinetics and thermal behaviour of the structure formation process in HMP/sucrose gelation. AB - The concentration and temperature dependence of the gelation kinetics of high methoxyl pectin (HMP; 60% sucrose, pH 3) was investigated using measurements of small-amplitude oscillatory shear. The rate of gelation close to the gel point can be described as a second-order rate process using the kinetic model of Ross Murphy (Carbohydr. Polym. 1991, 14, 281) and a critical exponent close to that predicted by the percolation approach. The modulus after a long ageing time showed a power concentration dependence with an exponent around 3.1, higher than the classical square of concentration dependence, which was probably either due to the nonequilibrium state of the HMP gels even after long ageing times, or due to the proximity of the concentration range studied to the critical gelling concentration. The gelation rate of HMP/sucrose systems is strongly dependent on the temperature. An Arrhenius relationship was applied to describe this dependence. Two different processes are proposed to explain the discontinuity observed, each one having rates with different temperature dependence. The applicable kinetics at longer times are quite different, with a lower dependence on polymer concentration and ageing temperature. A non-isothermal kinetic model was used to describe the gelation process of the HMP/sucrose system during cooling. PMID- 7772560 TI - Temperature variation of the relaxation time of alpha-dispersion for gamma irradiated collagen. AB - The effect of gamma irradiation, with doses from 10(2) to 10(3) kGy, on the dielectric relaxation time of solid-state collagen was studied. Temperature measurements of the relaxation time were made over a range of frequency of the electric field from 10(1) to 10(5) Hz and at temperatures from 298 to 480 K. The samples contained 0.06 g H2O/g dry collagen. The dependencies obtained indicate that values for the relaxation time decrease with increasing temperature for all samples of collagen. In addition, an increase in the irradiation dose resulted in a decreased relaxation time for collagen at each temperature studied. These changes can be interpreted on the basis of proton conduction processes. Such effects occurring in a heterogeneous medium such as a collagen-water system are caused by the localized jumping of free protons between neighbouring sites. In the system of irradiated collagen studied, the sites are formed by structural water molecules, the products of its radiolysis and also by elements of the damaged first-order structure of the collagen macromolecule. PMID- 7772561 TI - Effect of acetylation on conformation and bilirubin-binding properties of goat serum albumin. AB - Four acetylated derivatives of goat serum albumin with percentage modifications of 18, 40, 53 and 93% were checked for bilirubin-binding and conformational properties. Acetylation caused marked changes in protein conformation, as evidenced by double immunodiffusion and proteolytic digestion results, as well as a decrease in bilirubin binding. An increase in ionic strength had a dramatic effect on the bilirubin-binding characteristics of modified proteins. The results suggest that the lysine residues of goat serum albumin modified in this study are not involved in bilirubin-albumin interaction. PMID- 7772562 TI - Identification of framework residues required to restore antigen binding during reshaping of a monoclonal antibody against the glycoprotein gB of human cytomegalovirus. AB - Introduction of the complementary determining regions (CDRs) from a murine antibody to a human monoclonal antibody is an important technique (humanization) in the development of human immunotherapeutics. We have humanized murine monoclonal antibody HCMV37 which binds to the gB envelope glycoprotein of human cytomegalovirus. Simple transfer of the murine HCMV37 CDRs into heavy- and light chain framework regions (FRs) based on human NEW and REI, respectively, together with human IgGI and K constant regions, abolished antigen binding because of a suboptimal heavy chain. Replacement of human VH amino acids Leu70, Val71 and Arg94 with murine residues Thr70, Arg71 and Asn94 was insufficient to improve affinity. However, significant restoration of binding was obtained by substitution of human VH amino acids Thr28, Phe29, Ser30 with murine residues Ser28, Ile29, Thr30, in conjunction with the position 94 change. Residue 71, often regarded as critical for antigen binding, was not a major factor. PMID- 7772563 TI - Denaturation of horseradish peroxidase with urea and guanidine hydrochloride. AB - Favourable effects of urea and guanidine hydrochloride (Gdn HCl) on solubilization of the polar, non-polar and peptide groups of horseradish peroxidase (HRP), an example of a globular protein, provide the driving force for unfolding of HRP, in a reversible two-state process. The intrinsic or conformational stability of HRP at various pH values and temperatures has been estimated by the linear extrapolation method (LEM), a denaturant binding model (DBM) and Tanford's model. There is good agreement between these methods. Tanford's model shows that urea interacts with non-polar groups to a greater extent than Gdn HCl does, whereas Gdn HCl interacts more effectively with the peptide groups of HRP. PMID- 7772564 TI - Molecular interaction of tubulin with 1-deaza-7,8-dihydropteridines: a comparative study of enantiomers NSC 613862 (S) and NSC 613863 (R) by Raman and Fourier transform infrared spectroscopy. AB - Pre-resonance Raman spectroscopy has been applied to compare the vibrational modes of the R and S chiral isomers of 1-deaza-7,8-dihydropteridine when they are bound to tubulin. The main Raman bands are due to the chromophore and are coupled with the pi-pi electronic transition of C = C and C = N vibrational stretching. On binding to tubulin, the Raman spectra of both isomers are modified. However, the modifications induced are different for each isomer. The Raman bands due to C = C stretching from the phenyl ring are more strongly modified for the bound R isomer than for the S isomer. This leads us to suggest that R and S isomers differ in terms of their orientation in front of the binding locus of tubulin. In fact, with respect to the orientation of the bulky methyl group, the chromophore of the R isomer is more likely to be positioned against the external surface of either tubulin or GTPase proteins, while that of the S isomer is likely to be positioned away from the surface. The conformational changes induced in tubulin by R and S isomers have also been studied by Fourier transform infrared spectroscopy and by the analysis of amide I and II absorption bands. Both enantiomers induce similar minor changes to the tubulin secondary structure, corresponding to a decrease in the disordered alpha-helical content and accompanied by an increase in the undefined conformation content. PMID- 7772566 TI - Biodegradable polymers as biomaterials. AB - Biomaterials are used in prostheses and medical devices for different purposes. Polymers are the most diverse class of biomaterials. All biomaterials must meet certain criteria and regulatory requirements before they can be qualified for use in medical applications. Biocompatibility is one of the most important requirements. Both nondegradable polymers are designed to degrade in vivo in a controlled manner over a predetermined time. The main mechanism of in vivo degradation of polymers is 'hydrolytic degradation', in which enzymes may also play a role (i.e. 'enzymatic degradation'). Both natural e.g., collagen, and synthetic e.g., poly(alpha-hydroxy) acids, biodegradable polymers are used in biomedical applications. Many of the current polymers and processing techniques need to be improved in order to produce polymers with better performance in biological media. An important trend in related research and development is the synthesis of novel polymers, which would exhibit improved biocompatibility, and be bioresponsive. PMID- 7772565 TI - Synthesis of high-molecular-weight poly([R]-(-)-3-hydroxybutyrate) in transgenic Arabidopsis thaliana plant cells. AB - High-molecular-weight poly([R]-(-)-3-hydroxybutyrate) (PHB), a biodegradable thermoplastic, was produced from a suspension culture of transgenic Arabidopsis thaliana plant cells expressing two genes from the bacterium Alcaligenes eutrophus involved in the synthesis of PHB. The molecular structure of the plant produced polymer was analysed by gas chromatography, mass spectrometry, proton nuclear magnetic resonance spectroscopy, infra-red spectroscopy, spectropolarimetry, differential scanning calorimetry, X-ray diffraction and size exclusion chromatography. The results indicate that the polymer from transgenic plants appears to have a chemical structure identical to that of PHB produced by bacteria. However, the molecular weight distribution of the plant-produced PHB was much broader than that of typical bacterial PHB. PMID- 7772567 TI - In vitro study of biodegradation of a Co-Cr alloy using a human cell culture model. AB - The evaluation of a potential biomaterial is based on two approaches: firstly, the study of the local and systemic effects of the biomaterial implanted in the host; and secondly the study of the behaviour of the biomaterial itself with increasing time. The progress achieved in human cell culturing allows in vitro evaluation of a new biomaterial using the human cell(s) system(s) characteristic of the tissue which it will be exposed to in vivo. This kind of approach permits the assessment of the biodegradation of a biomaterial whatever it is: metal; alloy; ceramic; glass; polymer; with or without specialized coating.... The experimental approach is as follows: discs representative of the biomaterial (surface state, cleaning, sterilization process) are manufactured in order to cover the bottom of the culture wells. Thereafter, they are either brought in the presence of complete culture medium alone, or in the presence of a subconfluent cell layer. A kinetic analysis is performed using various incubation periods at 37 degrees C. Released biodegradation products are identified and quantified, in both the medium and cell compartment, and on the other hand cytotoxicity is assessed. A Co-Cr alloy was studied over a 9-day period according to the experimental schedule, and showed a higher corrosion rate in the presence of osteoblasts in the range of 25-30%. Moreover, an intracellular uptake of both Cr and Co was detected, which will have physiological importance. PMID- 7772568 TI - Rifampicin-carrying poly(D,L-lactide) microspheres: loading and release. AB - Rifampicin-loaded poly(D,L-lactide) (PDLLA) microspheres in the size range of 0.8 8.0 microns were prepared by a modified solvent evaporation method. Rifampicin loading was changed by using different types of solvents (i.e. methylene chloride, chloroform, and carbon tetrachloride) with different solvent/polymer ratios and different emulsifiers (i.e. methyl cellulose, gelatin, and Tween-20), and by changing the initial drug/polymer ratio. These rifampicin-loaded PDLLA microspheres degraded much faster in the medium at basic pH (9.8) and at high temperatures (55 degrees C). Rifampicin release was also high under these conditions. It was concluded that rifampicin release was both degradation- and diffusion-controlled. PMID- 7772569 TI - Test methodology for characterizing in vitro biodegradation. AB - In this paper mechanical tests for the characterization of the time-dependent behaviour of absorbable osteosynthetic materials are described. The tensile test is performed according to International Standard Organization (ISO) 3268/1978 and provides Young's modulus, tensile strength, elongation at tensile strength, and rupture force. The bending test is performed according to ISO 178/1975 and gives the flexural stress at various deflections, the force and deflection at break and the initial bending modulus. The torsional test is carried out according to ISO 458-1 and gives torsional load. The bending and torsional stress relaxation are measured. Relaxation modulus and the creep compliance are then determined. The parameters to be recorded in a cyclic bending test include the number of cycles or, in the case of sample survival, the remaining force at break at a bending test. The cyclic torsion test is carried out according to ISO 537/1989. The parameters to be recorded are the number of cycles or, in case of sample survival, the remaining force at a torsional test at 45 deg. Simulation tests provide a comparative assessment of the degradation phenomena under cyclic mechanical loading in bending or in torsion at elevated temperatures. PMID- 7772571 TI - Degradation and drug release characteristics of monosize polyethylcyanoacrylate microspheres. AB - Monosize, biodegradable poly(ethylcyanoacrylate) (PECA) microspheres with a diameter of 1.3 microns were prepared by a relatively new polymerization method, the so-called phase inversion polymerization. The effects of pH and temperature on the degradation behavior of PECA particles were investigated. PECA microspheres were degraded mainly by surface erosion. The degradation rate increased with increasing pH temperature. A model drug, i.e. 2,4 dinitrophenylhydrazine (DNPH) was loaded into the monosize PECA microspheres during polymerization. The drug incorporation into the PECA microspheres increased with increasing initial drug concentration in the monomer phase. Drug release from the PECA microspheres was investigated at different pH. Higher drug release rates were observed in the neutral and alkaline media as compared with the acidic medium. PMID- 7772570 TI - Degradation behaviour of ionic stepwise polyaddition polymers of medical interest. AB - The aim of this presentation is to review some of our recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest. PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides. There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioetheramine)s (PSTAs). Most of the PAAs exhibit heparin complexing ability. PAAs are also being considered as soluble carriers for delivering anti-cancer drugs. Some of these polymers have been studied as antimicrobial agents. PAAs with different structures degrade at different rates under physiological conditions. The degradation rate is also strongly influenced by pH. The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ultimately degrade to oligomeric products, while the quaternized PAAs do rapidly degrade. PMID- 7772572 TI - 20 MHz sonography, colorimetry and image analysis in the evaluation of psoriasis vulgaris. AB - For objective evaluation of the treatment of psoriasis vulgaris standard techniques are desirable. They should be reproducible, sensitive and non invasive. In this study non-invasive bioengineering techniques, especially high frequency/high resolution ultrasound for measurement of the healing of psoriasis vulgaris were evaluated. Fifty patients with chronic stationary plaque type psoriasis participated in a prospective study; in each patient two psoriatic plaques were examined by means of sonography, colorimetry and image analysis during treatment until complete resolution had occurred. Skin thickness and density could be quantified by means of high frequency ultrasound. In active psoriatic lesions, an echopoor area underneath the entry echo in the ultrasound image caused by acanthosis and inflammatory infiltrate is typical. Under therapy the thickness of this echopoor area diminishes while its density increases. Intensity of the erythema especially the decrease of erythema through healing could not exactly be quantified with the colorimeter because the 'Lab'-CIE-colour representation system cannot distinguish well enough between the colours red and brown. Image analysis allowed to measure the sizes of the psoriatic plaques and to quantify their resolution under therapy. The measuring of plaque size by the aid of computer based image analysis is possible and useful. PMID- 7772573 TI - Involvement of protein kinase C in bradykinin-induced intracellular calcium increase in primary cultured human keratinocytes. AB - Bradykinin (BK) is one of the key mediators of inflammation and a weak mitogen. We have previously demonstrated that BK induced the generation of inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) which caused Ca2+ mobilization in human keratinocytes. In this study, BK-induced Ca2+ responses were examined in primary cultured human keratinocytes by video imaging fluorescence microscopy using fura 2. Intracellular calcium concentration ([Ca2+]i) level increased to a peak within 30 s after BK addition and decreased gradually to the basal level. The existence of the broad shoulder in the [Ca2+]i profile was suggested to be due to the Ca2+ influx from the external medium, because this disappeared in the presence of 0.5 mM EGTA. Pretreatment with phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, significantly resulted in reduction of the descending shoulder of BK-induced increase in [Ca2+]i. A 20-min pretreatment with PKC inhibitors, H-7 or staurosporine, reversed the decrease by PMA in the shoulder of BK-induced Ca2+ response. Furthermore, the BK-induced [45Ca] uptake was inhibited by EGTA and PMA. Ins(1,4,5)P3 generation induced by BK peaked at 20 s and returned to the basal level at 60 s. There were no significant differences in Ins(1,4,5)P3 levels at 20 and 60 s among the cells exposed to BK alone, BK with PMA pretreatment (20 min) and BK with PMA+H-7 pretreatment. These results suggest that the BK-induced Ca2+ influx, which was shown as shoulder, may be negatively modulated by PKC in primary cultured human keratinocytes. PMID- 7772574 TI - The effect of anemia on skin blood flow in human. AB - The skin blood flow in the deltoid region was measured in 78 males by the Xenon 133 clearance method. A correlation was then made between age, hematocrit value, hemoglobin value and total protein determined at the time of skin blood flow measurement. From the data obtained, the following conclusions could be drawn: (1) skin blood flow significantly decreased with increasing age and with decreasing hematocrit and hemoglobin values; (2) skin blood flow showed the closest correlation with age (P < 0.001) and a weaker correlation (P < 0.01) with hematocrit and hemoglobin; (3) total protein demonstrated a significant decrease (P < 0.01) with a decrease in hematocrit and hemoglobin values giving rise to hypoproteinemia. PMID- 7772575 TI - Keratinocytes differentiate in response to inhibitors of deoxyribonucleotide synthesis. AB - We previously reported that methotrexate (MTX) caused an irreversible inhibition of growth and induced terminal differentiation of human keratinocytes. These effects of methotrexate were prevented by thymidine and thus, were attributed to depletion of thymine deoxyribonucleotides. The purpose of the research reported in this paper was to determine whether differentiation was induced by the general class of agents which are known to interfere with synthesis or utilization of deoxyribonucleotides. Agents examined included 5-fluorouracil, 5 bromodeoxyuridine, hydroxyurea, high-dose thymidine, aphidicolin, and AG#85, a newly reported thymidylate synthase inhibitor. All these agents increased the expression of involucrin and increased the amount of cornified envelope protein at doses that inhibited proliferation by > 75%. We demonstrated, however, that in our cell culture system not all conditions producing inhibition of proliferation induced differentiation; withdrawal of growth factors and supplemental amino acids inhibited proliferation but did not increase involucrin expression or production of cornified envelope protein. PMID- 7772576 TI - The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan. AB - To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging; (3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid. PMID- 7772577 TI - Modulation of collagen synthesis and cell proliferation by retinoids in human skin fibroblasts. AB - The effect of the retinoids, 13-cis-retinoic acid (-RA), etretinate and all-trans RA on collagen synthesis and cell proliferation of human skin fibroblasts was studied. These compounds all inhibited collagen synthesis at concentrations between 10(-8) and 10(-5) M after 48 h treatments. The inhibitory effect of 13 cis-RA was the most pronounced. Both all-trans-RA and etretinate inhibited DNA synthesis, to 60% and 53% of control value, respectively, at 10(-5) M. In contrast, 13-cis-RA did not show any significant effect on DNA synthesis at the concentrations used. 13-cis-RA appears to be a unique drug showing a pronounced inhibitor effect on collagen synthesis without affecting DNA synthesis and may prove a useful tool for the treatment of fibrotic diseases. PMID- 7772578 TI - Photoaging from an oxidative standpoint. AB - The free radical theory proposes that photoaging, which is both qualitatively and quantitatively different from chronological aging, may result from imperfect protection against cumulative stress of free radicals produced by chronic and repeated ultraviolet irradiation. Since the skin is always in contact with oxygen and is occasionally exposed to ultraviolet light, skin is one of the best target organs of environmental photo-oxidative stress. A growing body of evidence suggests that reactive oxygen species are generated by ultraviolet irradiation resulting in the structural and functional alteration of cutaneous components which should affect the photoaging process over a long period. The age-related alteration of cutaneous antioxidant defense capacity against cumulative effects of continual photo-oxidative stress to the skin may also affect the photoaging. Thus the possible use of antioxidants that attenuate photo-oxidative toxicity is believed to be an important strategy modulating photoaging. Several antioxidants have readily been proved to work in the experimental conditions. This paper reviews photoaging from a photo-oxidative standpoint and discusses the possible regulation of photoaging by antioxidants that is an important issue in the photodermatological field. PMID- 7772579 TI - Effect of ultraviolet A on IL-1 production by ultraviolet B in cultured human keratinocytes. AB - Human skin is exposed to significant amounts of UVA and UVB radiation simultaneously. The effects of UVA and UVB interactions have been examined in many aspects such as erythema response. The effects of UVA on the production of cytokines by UVB have not been studied yet. The purpose of this study is to observe the effect of UVB and UVA on the production of IL-1 in cultured human keratinocytes and to determine whether UVA can modify the effects of UVB on the IL-1 production. Human keratinocytes derived from normal foreskin were exposed to UVA (0-30 J/cm2) and subsequently to UVB (0-50 mJ/cm2). After 48 h incubation, IL 1 levels in the culture supernatants and cell extracts of the cultured keratinocytes were measured by thymocyte proliferation assay. We have observed that UVB increased the production of IL-1 in cultured keratinocytes. However, UVA suppressed the production of IL-1 and also the stimulatory effect of UVB on the IL-1 production. We think that the opposite effects of UVB and UVA on the IL-1 production in human keratinocytes might explain the different action mechanisms of UVB and UVA in many cutaneous responses. PMID- 7772580 TI - Sequence analysis and characterization of FAR-17c, an androgen-dependent gene in the flank organs of hamsters. AB - This study reports on the isolation and characterization of a cDNA clone, regulated by androgen transcriptionally, in male Golden hamsters' flank organs. Previous studies have reported on the cloning of an androgen-dependent gene, FAR 17a, from the same hamster organ. After castration, the FAR-17c transcription rate decreases faster than FAR-17a but is not suppressed completely. The recovery of transcription by androgen injection is also faster than FAR-17a. In male hamsters, it is expressed strongly in the sebaceous glands and liver, and weakly in the lungs and brain. It has never been expressed in the testes. In the female, it is strongly expressed in the liver and brain and weakly in the lungs and flank organs. Sequence analysis shows that FAR-17c has a long 1062 bp open reading frame and its deduced amino acid sequence (354 residues) is highly homologous to the stearyl-CoA desaturases of the rat liver and mouse adipocytes. Stearyl-CoA desaturase, either in the liver or adipocytes appears to be independent of androgen regulation. Since stearyl-CoA desaturase plays a key role in fatty acid metabolism, further studies on its regulation by androgen are warranted in relation to acne vulgaris. PMID- 7772581 TI - Thromboembolic disease and thromboprophylaxis in oral and maxillofacial surgery: experience and practice. AB - OBJECTIVE: (i) To determine the incidence of thromboembolic disease (TED) in major maxillofacial surgery and in particular deep vein thrombosis (DVT) and pulmonary embolism (PE). (ii) To determine current thromboprophylactic practice in the specialty. DESIGN: Retrospective survey by questionnaire of five year experience and current practice in UK maxillofacial surgical units. SUBJECTS: The patients of 130 consultants carrying out major maxillofacial surgery. MAIN OUTCOME MEASURES: (i) The number of cases of fatal and non-fatal PE and the number of diagnosed cases of DVT not progressing to PE. (ii) The frequency of use of mechanical and pharmacological thromboprophylactic measures. RESULTS: (i) There was a 79% return of questionnaires and from these were reported 60 cases of PE of which 14 were fatal with 64 cases of DVT not progressing to PE. Of the PE group almost 60% followed operations for orocervical malignancy while 25% were related to maxillofacial trauma. 64% of respondents had encountered no episodes of perioperative DVT and 68% no cases of PE. (ii) Mechanical thromboprophylactic measures included the use by 76% of respondents of a graduated compression garment, ripple mattress by 47% and intermittent inter-operative calf pressure by 38.5%. Of pharmacological agents 45% used low dose heparin, 14.5% a dextran infusion and 6% an antiplatelet agent. 58.3% gave advice about smoking and 37.5% recommended temporary discontinuation of the contraceptive pill. CONCLUSIONS: The incidence of DVT and PE in major maxillofacial surgery is low. Nevertheless it is recommended that there is rigid compliance with the recommendations for surgery in general from the thromboembolic risk factors consensus group (THRIFT) and from similar groups in Europe and the USA. PMID- 7772582 TI - Protective ptosis after parotid surgery induced with botulinum toxin. PMID- 7772583 TI - 'Hydroplastic'--a new material for orthognathic surgical splints. PMID- 7772584 TI - Recording the facial midline for orthognathic planning. PMID- 7772585 TI - Down Surgical Prize 1994: Mr L.D. Finch FRCSED, FDSRCSED. PMID- 7772586 TI - Full thickness skin grafting for donor defect repair. PMID- 7772587 TI - The diagnostic yield of only one occipitomental radiograph in cases of suspected midfacial trauma. PMID- 7772588 TI - Percutaneous subcricoid dilatational tracheostomy. PMID- 7772589 TI - Future of biodegradable osteosynthesis in maxillofacial fracture surgery. PMID- 7772590 TI - Convergence insufficiency and failure of accommodation following midfacial trauma. AB - A prospective evaluation of patients who had sustained midfacial trauma was carried out in order to determine the prevalence of impaired convergence and accommodation and to establish the risk factors for such defects. Of 52 patients in this study, 11 suffered accommodation and/or convergence disturbances. They included 6 males (17% of the male population) and 5 females (29% of the female population). Nine of these 11 patients sustained their injuries due to alleged assaults (24.3% of all assaulted patients) and 2 following simple falls (25% of all fall victims). Five patients complained of double vision for near (5/11 = 45.5%) and another 4 had blurred vision and/or difficulty with reading (4/11 = 36.4%). The remaining two were asymptomatic. Six patients were randomly selected to receive orthoptic exercises/treatment while the other five were monitored for signs of spontaneous recovery. Within six months of injury/surgery, 83% of the treated patients (n = 5) and 80% of the non-treated patients (n = 4) recovered to within the normal values of accommodation and convergence. No significant statistical relationship was found between the incidence of accommodation and/or convergence failure, and the cause or the type of fracture sustained. It may, however, be related to the severity of both the impact and the associated closed head trauma. PMID- 7772591 TI - The management of soft tissue facial wounds. AB - The physiological and physical principles involved in the management of facial lacerations are reviewed. Because there have been no previously published descriptions of the actual problems encountered in clinical practice in A & E Departments, a prospective clinical survey of 100 consecutive patients with facial lacerations repaired by oral & maxillofacial house surgeons was undertaken and a series of lacerations was studied in detail. These included periorbital, nasal, labial and neck injuries. High magnification revealed irregularity of wound margins in almost all cases, frequent localised ischaemia, necrosis, localised dehiscence and infection or inadequate closure. Because all of these problems are likely to increase scarring and deformity, this study suggests the need for a re-appraisal of the management of facial lacerations, particularly in relation to local skin edge excision, prevention of infection, and the use of magnification during closure. PMID- 7772592 TI - Morphological and morphometric studies of exfoliated oral squames from chronic inflammatory oral ulcers using light and scanning electron microscopy. AB - The morphological and morphometric features of exfoliated squames from the margins of chronic oral ulcers were studied by light and scanning electron microscopy. A variety of features consistent with a mixture of degenerative changes and regenerative activity were observed. None was sufficiently reliable to distinguish chronic inflammatory from malignant ulcers. PMID- 7772593 TI - The diagnostic yield of only one occipito-mental radiograph in cases of suspected midfacial trauma--or is one enough? AB - The number of radiographic examinations should be reduced to clinical needs. Often in cases of suspected midfacial injury three views comprise a routine 'facial view' survey. A reduction in patient radiation exposure and X-ray costs would be achieved if only one occipito-mental radiograph was used. In this study the ability of Accident and Emergency staff to diagnose the presence of fractures using the standard occipito-mental view was assessed. The specificity value was 90% and the sensitivity was 75%. Few fractures were missed on initial scrutiny and in cases of doubt further views would be requested. Therefore the findings would suggest that only one view is sufficient for routine assessment. PMID- 7772594 TI - Augmentation of the atrophic maxillary alveolar ridge with hydroxyapatite granules in a Vicryl (polyglactin 910) knitted tube and simultaneous open vestibuloplasty. AB - A modified technique for augmentation of the severely atrophic edentulous maxillary alveolar ridge is described. The augmentation was carried out using a knitted polyglactin 910 mesh tube filled with porous hydroxyapatite granules, the tube being inserted through the access achieved by an open vestibuloplasty. The results of an in-vivo animal study showed that the absorption of the mesh was complete between 49 and 70 days. The clinical study included 11 patients in all of whom there was severe maxillary ridge atrophy and major prosthetic problems; follow-up was for a mean of 25 months. The procedure was without significant complication and produced a mean immediate absolute augmentation of 5.5 mm and substantially increased vestibular depth. A gradual reduction of ridge height was found over time. Nevertheless all patients showed significantly increased ability to wear their dentures. The technique is presented as a safe and predictable alternative to the use of bone grafts and titanium implants in these severely atrophic cases. PMID- 7772595 TI - Unusual presentation of Paget's disease of the maxilla. AB - Paget's disease is a disorder of bone metabolism that is relatively common in the elderly population. The jaw bones are affected in 17% of cases. A case of maxillary involvement with unusual clinical and radiographic findings is presented. PMID- 7772597 TI - Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. AB - HeLa cell extract was separated by 7% polyacrylamide gel electrophoresis without SDS and subsequently stained with anti-nucleophosmin/B23 (NPM) antibody in a Western blot analysis. Two immunobands were obtained. The major band with a slower electromobility (RF = 0.23) is the NPM oligomer, while the fast-moving minor band is the monomer (RF = 0.56). The oligomer constitutes about 95% of total NPM. The oligomer sedimented faster (10 s) than the monomer in sucrose density gradient centrifugation. Three oligomer bands were identified. NPM oligomer is not affected by treatments with DNase. RNase, 10 mM EDTA, 1 M NaCl, and lyophilization. However, 3 M urea causes reversible dissociation of NPM oligomer into monomer. The level of NPM oligomer remains unchanged in HeLa cells after treatment with the cytotoxic agents, actinomycin D, toyocamycin and camptothecin. These results indicate that NPM oligomer is the major and stable NPM entity in HeLa cells. PMID- 7772596 TI - Eukaryotic DNA topoisomerases I. PMID- 7772598 TI - Differential display analysis of gene expression in developing embryos of Xenopus laevis. AB - Differential display (DD), an arbitrarily primed RT-PCR fingerprinting technique, is a novel approach for the search of differentially expressed transcripts. Using our improved DD protocol, reproducible cDNA fingerprints were successfully obtained from RNAs of Xenopus laevis embryos at six representative stages. Parallel comparison among the fingerprints revealed a number of bands with differential expression patterns. Analysis with clones of three randomly chosen bands confirmed that their expression patterns were faithfully reflected on fingerprints, thereby proving the reliability and validity of the approach. Nucleotide sequencing of these clones revealed that one is identical with a known transcript (cardiac actin), the second is a novel developmentally regulated gene showing no significant homology with those reported previously, and the last is a close but unique relative of XK endo B gene showing somewhat different spatial expression pattern. These results indicated that the DD analysis provides a rapid and reliable way for the identification of novel differentially expressed genes as well as a unique 'scope' for the survey of the changes in overall gene expression profiles occurring in the early embryonic development of Xenopus as well as of other organisms. PMID- 7772599 TI - Effect of cations on the volume of the helix-coil transition of poly[d(A-T)]. AB - The pressure dependence of the helix-coil transition temperature of poly[d(A-T)] has been measured in aqueous solutions of NaCl, KCl, and CsCl at concentrations between 0.02 and 1 M. In all cases the transition temperature increases with pressure. For solutions of NaCl, KCl and dilute CsCl the change in the transition temperature is linear with pressure up to 200 MPa. In more concentrated CsCl solutions the change in Tm with pressure was hyperbolic. The molar volume change of the transition (delta Vt) was calculated using the Clapeyron equation. At the lower salt concentrations, the derived values of delta Vt increase with the radius of the cation (Na+ < K+ < Cs+). At the higher salt concentrations delta Vt of poly[d(A-T)] in Na+ and K+ became equal; however, in CsCl solutions delta Vt was approximately twice as large as delta Vt in solutions containing the other two ions. In solutions of NaCl and KCl, delta Vt increased linearly with the logarithm of the salt concentration while in aqueous CsCl the concentration dependence of delta Vt was hyperbolic. The results are interpreted in terms of the role played by the radius of the cation in deciding the strength of the interactions formed with water. PMID- 7772600 TI - Topoisomerase activity associated with polyoma virus large tumor antigen. AB - Polyomavirus (Py) large tumor antigen (LT) was produced in mammalian or insect cells infected with a suitable viral expression vector, and purified by a procedure combining immunoprecipitation with ion-exchange chromatography. Fractions containing the bulk of LT displayed a DNA-relaxing activity (LT-topo) which could be attributed neither to topoisomerase II (topo II) nor to topoisomerase I (topo I) encoded by the cell or the viral vector. On the one hand, LT-topo relaxed pBR322 DNA in a reaction which, unlike that characteristic of topo II, was ATP-independent and inhibited by camptothecin. On the other hand, serum from scleroderma patients which strongly inhibited calf thymus topo I had no effect on LT-topo, which absolutely required Mg2+ ions to relax DNA. Thus, LT topo is either inherent to LT or belongs to a LT-bound enzyme similar to, but distinct from, topo I. PMID- 7772601 TI - Cloning, sequencing and expression of the L5, L21, L27a, L28, S5, S9, S10 and S29 human ribosomal protein mRNAs. AB - During systematic analysis of the mRNAs expressed in a human colorectal carcinoma with the aim of evidencing new makers of the disease (Frigerio et al. (1995), in press), we isolated several clones corresponding to homologs of rat ribosomal protein mRNAs L5, L21, L27a, L28, S5, S9, S10 and S29. Because expression of several mRNAs encoding ribosomal proteins was found strongly altered during colorectal carcinogenesis, sequence of these transcripts, not previously described in human, was completed and their expression analyzed. Northern blot analysis of RNAs extracted from colorectal cancer and ajdacent normal tissue from 6 patients revealed in all of them perturbations of expression in cancer, compared to normal. No correlation could however be made between the level of expression and the severity of the disease. Yet, abnormal patterns with additional larger transcripts were observed in some patients for rpL5, rpL28 and rpS10. PMID- 7772602 TI - Sequence of the gat operon for galactitol utilization from a wild-type strain EC3132 of Escherichia coli. AB - The sequence of the gat operon for galactitol (Gat) utilization from a wild-type isolate of Escherichia coli, strain EC3132, is presented. The operon comprises 7 open reading frames (ORFs) called gatYZABCDR. The genes are transcribed from a promoter located upstream of gatY. Genes gatABC encode the substrate-specific domains IIA, IIB and IIC of a galactitol-specific Enzyme II (EIIGat) of the phospho enol pyruvate-dependent carbohydrate:phosphotransferase system (PTS); gatD encodes an NAD-dependent Gat 1-phosphate dehydrogenase; and gatY an enzyme which hydrolyses tagatose 1,6-bisphosphate; gene gatZ is required in a cell to show a Gat+ phenotype, but its physiological function has not yet been identified; gatR encodes a repressor for the gat operon. All genes are highly similar to the gat genes from E. coli K-12; in this organism they map at 46.70 min of the gene map, equivalent to about 2180-2186 kbp. PMID- 7772603 TI - Nucleotide sequence of the Staphylococcus aureus RNA polymerase rpoB gene and comparison of its predicted amino acid sequence with those of other bacteria. AB - The complete nucleotide sequence of the rpoB gene which encodes the beta subunit of S. aureus RNA polymerase has been determined. The RpoB protein, consists of 1182 amino acids and has a novel initiation codon UUG which initiates protein synthesis with methionine. There is a very strong Shine-Dalgarno complementarity and the -10 and -35 promoter hexameric sequences are TAATAT and CCGTTT, respectively. A rho-dependent termination site, CAATCAA, is present which overlaps the -35 promoter sequence of the adjacent rpoC gene a feature which may have a role in the co-ordinate expression of the two genes. A strong homology and conserved regions were found to exist over the predicted amino acid sequences coding for S. aureus rpoB and the equivalent proteins in Escherichia coli, Pseudomonas putida, Salmonella typhimurium, Chlamydia trachomatis, cyanobacterium Anabaena sp. strain PCC 7120. PMID- 7772604 TI - Cloning and characterization of rat cysteine sulfinic acid decarboxylase. AB - Cysteine sulfinic acid decarboxylase (CSAD) is a key enzyme in taurine biosynthesis. CSAD activity and enzyme protein concentration are both repressed by the action of the steroid family hormones triiodothyronine and estrogen. To characterize this suppression, a cDNA clone for CSAD was isolated from a rat liver cDNA expression library using polyclonal antibodies to CSAD. The cDNA was sequenced in its entirety and confirmed to be a clone of CSAD. In a Northern blot comparing liver and kidney RNA of male and female rats, the CSAD cDNA probe detected a 2.5 kb mRNA band which was present at levels corresponding to the concentration of enzyme protein. Hyperthyroidism decreased CSAD mRNA as compared to euthyroid controls, providing evidence that negative regulation of CSAD activity occurs at the level of mRNA. PMID- 7772605 TI - Nucleotide sequence of ornithine decarboxylase antizyme cDNA from Xenopus laevis. AB - An ornithine decarboxylase antizyme cDNA was obtained from Xenopus laevis liver and its sequence was determined. The cDNA consists of two major open reading frames as found in mammalian antizymes, which require +1 ribosomal frameshifting for its translation. Sequences important for frameshifting, namely the frameshift site and downstream stimulatory pseudoknot determined in the rat mRNA, are conserved. PMID- 7772606 TI - A cDNA of Schizosaccharomyces pombe encoding a homologue of DnaJ-like protein. AB - A Schizosaccharomyces pombe homologue, Psi, was cloned from Schizosaccharomyces pombe cDNA library. Deduced amino acid sequence of the cDNA has 55% sequence homology with the Saccharomyces cerevisiae Sis1 protein and contains the structural features of a family of DnaJ proteins. This homology suggests Psi protein may be implicated in the initiation of translation as like Sis1 function of Saccharomyces cerevisiae. PMID- 7772607 TI - Molecular cloning, sequencing and expression of a cDNA encoding a human liver NAD dependent alpha-glycerol-3-phosphate dehydrogenase. AB - This work reports the primary nucleotide structure and in vitro translation of a cDNA, expressed by a gene mapping on chromosome 12, that encodes a human hepatic alpha-glycerol-3-phosphate dehydrogenase (L-glycerol-3-phosphate:NAD oxidoreductase, E.C. 1.1.1.8). The 1413 bp cDNA comprises an ORF of 1050 bp that encodes a 349 amino acid protein of 37.5 kDa. Northern blot analysis of poly(A)+ mRNA from human liver showed three transcripts, while from human placenta only two transcripts were detected. PMID- 7772609 TI - Isolation and characterization of the gene encoding the Drosophila melanogaster transcriptional elongation factor, TFIIS. AB - We have characterized a genomic clone encoding the Drosophila melanogaster transcriptional elongation factor, TFIIS. The coding region of the TFIIS gene is interrupted by a short intron. The potential promoter region, deduced from the determination of the transcription start point (tsp), lacks distinct TATAAA or CCAAT box consensus sequences. Southern analysis and the in situ hybridization to chromosomes suggests that it is single-copy gene which is localized to the 35B region on the left arm of the second chromosome. PMID- 7772608 TI - XB/U-cadherin mRNA contains cytoplasmic polyadenylation elements and is polyadenylated during oocyte maturation in Xenopus laevis. AB - Cytoplasmic polyadenylation elements (CPE) are distinct sequence motifs in the 3' untranslated region of mRNAs. They control translation of these RNAs by cytoplasmic polyadenylation. We show that the mRNA of the cell adhesion molecule XB/U-cadherin contains two CPE motifs. With oocyte maturation this mRNA becomes polyadenylated and increasingly recruited into the polysomal fraction. Our results give evidence that CPEs of the XB/U-cadherin mRNA are responsible for the XB/U-cadherin protein increase during oocyte maturation. PMID- 7772610 TI - Social phobia. PMID- 7772611 TI - Classification and epidemiology of social phobia. AB - The individualization of social phobia among other phobic disorders is very recent, although previous clinical descriptions can be found in the literature. The new classifications (DSM-III, DSM-IV and ICD-10) have provided operationalized criteria for this disorder, which have allowed researchers to conduct epidemiological studies. However, some diagnostic issues are not completely solved, namely, those with other boundary disorders. Cross-cultural prevalence and risk factors of social phobia are reviewed. Results of a French community study have found a lifetime prevalence rate of 2.1% in males and 5.4% in females. Comorbidity of social phobia with other anxiety disorders and major depression was high. Suicidal tendencies, family history and health services utilization were analyzed according to the lifetime comorbidity pattern of social phobia and depression. PMID- 7772612 TI - Comorbidity and social phobia: evidence from clinical, epidemiologic, and genetic studies. AB - This paper reviews evidence from clinical, epidemiologic, and family studies regarding the association between social phobia and other syndromes. Social phobia is strongly associated with other anxiety disorders, substance abuse, and affective disorders in both clinical and community samples. An average of 80% of social phobics identified in community samples meet diagnostic criteria for another lifetime condition. Social phobia is most strongly associated with other subtypes of anxiety disorders, with an average of 50% of social phobics in the community reporting a concomitant anxiety disorder including another phobic disorder, generalized anxiety, or panic disorder. Approximately 20% of subjects in the community meet lifetime criteria for a major depressive disorder. The onset of social phobia generally precedes that of all other disorders, with the exception of simple phobia. Both clinical severity and treated prevalence are consistently greater among social phobics with comorbid disorders. The results of family and twin studies reveal that shared etiologic factors explain a substantial proportion of the comorbidity between social phobia and depression, whereas the association between social phobia and alcoholism derives from a nonfamilial causal relationship between the two conditions. Clinical and phenomenologic implications of these findings are discussed. PMID- 7772613 TI - Biological characterization of social phobia. AB - As social phobia has become clinically more clearly characterized, the search for biologic features of the disorder has been instituted. As with most psychiatric disorders, this undertaking is difficult, because of the heterogeneity of the disorder in affected individuals. However, with investigation into several different areas, i.e., the neuroendocrine system, neurotransmitter function via naturalistic challenges, chemical and pharmacologic probes, response to pharmacologic interventions, and neuroimaging, theories about the biologic characteristics of social phobia have been advanced. Neuroendocrine studies have not yet revealed any clear abnormalities specific to individuals with social phobia. Based on studies of neurotransmitter functions and pharmacologic response, the major neurotransmitter systems that have been implicated are the serotonergic, dopaminergic, and noradrenergic. Neuroimaging studies have demonstrated possible structural and metabolic differences in some patients with social phobia. PMID- 7772615 TI - Can digit symbol-verbal fluency comparisons facilitate detection of pseudodementia? A preliminary study. AB - Depressive psychomotor retardation may impair performance on timed tests. By comparison word association measures of verbal fluency are reportedly unaffected by depression. Comparisons of a brief psychomotor test with a measure of verbal fluency may therefore prove useful when there is a concern that depression may be undermining adaptive functioning, assuming both measures display: (1) broad spectrum sensitivity to brain impairment, (2) differential vulnerability to depression, and (3) moderate correlation in nondepressed persons. Digit Symbol (DS) and the "FAS" measure of verbal fluency are sensitive to genuine dementia, satisfying the first criterion. We found that depressed schizophrenics performed at significantly lower levels on DS, but not on FAS, than nondepressed schizophrenics. The two groups differed significantly on a discrepancy score derived by subtracting FAS from DS scores; normals obtained discrepancy scores highly similar to those of nondepressed schizophrenics. As the normals had higher DS and FAS scores, this discrepancy-score similarity suggests that this index may have wide application. The third criterion is satisfied by the findings of a 0.64 correlation between DS and FAS scores adjusted for age (DS and FAS) as well as gender and educational attainment (FAS) in nondepressed samples. Implications for further research and clinical applications are discussed. PMID- 7772614 TI - Recent developments in the psychopharmacology of social phobia. AB - The past 2 decades have witnessed an upsurge in the interest in anxiety disorders. Much research effort has been dedicated to panic disorder and obsessive-compulsive disorder. However, it is only very recently that we have begun to understand some of the basic principles about the psychopharmacology of social phobia. Drug classes thus far studied include beta-blockers, nonselective and irreversible monoamine oxidase inhibitors (MAOIs), and benzodiazepines. Beta blockers appear to be of use in specific social phobias, such as public speaking, whereas they are of little use in generalized social phobia. There is considerable evidence suggesting that MAOIs are effective in reducing both social anxiety as well as social avoidance in generalized social phobia. A disadvantage of the conventional irreversible MAOIs is their risk for hypertensive crises when combined with dietary tyramine. Thus far only a small number of studies with selective MAO-A inhibitors, such as moclobemide and brofaromine, have been conducted in social phobia, and the results indicate that both compounds are effective. Drugs exerting selective and specific actions on certain components of, for example, the serotonergic system, can now be studied, and it is hoped that the role of 5-hydroxytryptamine) and other neuronal systems in social phobia can be elucidated. In order to gain more information about selective serotonergic drugs, the first double-blind placebo-controlled study with fluvoxamine was recently published. Preliminary results indicate a reduction in social anxiety after a prolonged treatment period. Finally, the role of peptides in the treatment of social phobia is critically reviewed. The MSH/ACTH analog Org 2766 was investigated in patients suffering from social phobia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772616 TI - Mianserin treatment of patients with psychosis induced by antiparkinsonian drugs. AB - We evaluated the effects of mianserin, a relatively selective 5-HT2 receptor antagonist, on symptoms related to drug-induced psychosis in patients with Parkinson's disease (PD). A total of 12 patients with PD who had developed drug induced psychosis showed delirium (DSM-III-R criteria; n = 10) and pure visual hallucinations (n = 2). The antiparkinsonian drugs involved in the drug-induced psychosis were L-DOPA/carbidopa, bromocriptine, trihexyphenidyl, and amantadine. They received mianserin (mean 36.7 mg, range 20-60 mg) given orally for 8 weeks. Complete relief or marked improvement in psychotic symptoms was noted in 8 patients, moderate improvement in 2 patients, and no effect in 2 patients. The parkinsonian disability also decreased slightly in 8 patients. These results suggest that serotonin antagonism at 5-HT2 receptors may not only play an important role in the treatment of drug-induced psychosis in PD, but may also ameliorate the symptoms of parkinsonism. PMID- 7772618 TI - [Hepatitis A virus]. PMID- 7772619 TI - [Hepatitis B virus: biology, natural history, and diagnosis of the infection]. PMID- 7772617 TI - Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression. AB - This study was carried out to examine some components of in vivo immune function in major depression and schizophrenia. Toward this end, plasma concentrations of interleukin-1 beta (IL-1 beta) and IL-6, soluble IL-2 receptor (sIL-2R), and transferrin receptor (TfR) were measured in 28 normal controls, 11 schizophrenics and 13 major-depressed patients. Schizophrenic and major-depressed patients showed significantly higher plasma sIL-2R and TfR than normal controls. There was a trend toward higher plasma IL-6 in the psychiatric patients, and particularly in schizophrenic patients, than in normal volunteers. In normal controls and in the total study group, there were highly significant and positive correlations between plasma TfR and sIL-2R concentrations. It is suggested that schizophrenia and major depression are characterized by immune disorders that may indicate activation of cell-mediated immunity such as T-cell activation. PMID- 7772620 TI - [Hepatitis virus]. PMID- 7772622 TI - [Hepatitis D virus: biology, natural history, and laboratory diagnosis]. PMID- 7772621 TI - [Hepatitis C]. PMID- 7772623 TI - [Hepatitis E: enterically transmitted Non-A, Non-B hepatitis]. PMID- 7772624 TI - [Epidemiology of viral hepatitis]. PMID- 7772625 TI - [Prophylaxis of viral hepatitis]. PMID- 7772626 TI - [Clinical features of viral hepatitis. Acute hepatitis. Chronic hepatitis. Hepatocellular carcinoma]. PMID- 7772627 TI - Necrosectomy and laparostomy--a combined therapeutic concept in acute necrotising pancreatitis. AB - OBJECTIVE: To present our experience with laparostomy and necrosectomy in the treatment of acute necrotising pancreatitis, and to show how refinements in our treatment regimen improved mortality over the years despite no reduction in the severity of the disease. DESIGN: Retrospective study. SETTING: University hospital, Austria. SUBJECTS: 125 patients treated by laparostomy/necrosectomy with repeated revisions during the period January 1983 to December 1991. INTERVENTIONS: Laparostomy, blunt necrosectomy, operative lavage, and open drainage. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: The severity of disease was assessed by the APACHE II score (median 15, range 4-30). In 106 of the 125 patients (85%) the necrotic pancreatic tissue was infected. Patients were operated on if they deteriorated clinically or if organ failure was suspected. A change in the protocol from revisions on demand (1983/4) to planned re exploration at 48 hour intervals (1985/8) was associated with a reduction in mortality from 53% (16/30) to 28% (20/72). This was further reduced in 1989/91 to 17% (4/23) when a protocol of revisions planned for individual patients was introduced (p = 0.02). The incidence of gastrointestinal fistulas during the three periods was 6/30 (20%); 24/72 (33%); and 1/23 (4%); (p = 0.022), whereas that of intraabdominal bleeding remained much the same (7/23, 23%; 13/72, 18%; and 4/23, 17%; p = 0.56). The median (range) APACHE II scores for the three periods were 12 (4-27), 15 (5-30), and 14 (4-25). CONCLUSION: By continual revision of our protocol, together with accompanying improvements in intensive care, our mortality decreased significantly during the nine year period. PMID- 7772628 TI - Reduction of postoperative immunosuppression with ranitidine in patients with cancer of the stomach or large bowel. AB - OBJECTIVE: To assess the effect of ranitidine on cellular immune response (and postoperative infective morbidity) in a homogeneous group of patients. DESIGN: Prospective randomized controlled trial. SETTING: University hospital, Italy. SUBJECTS: 42 patients about to undergo curative resection for carcinoma of the colon, rectum, or stomach. INTERVENTIONS: Cell mediated immunity was tested 3 days before, and 4 days after, operation by reactions to 7 recall antigens (Multitest, Merieux). 21 patients were randomly allocated to receive ranitidine 100 mg twice daily intravenously from the day before operation until the third postoperative day. MAIN OUTCOME MEASURES: Comparison of the number of reactive patients and number of positive antigens before and after operation; and correlation between reactivity and incidence of postoperative infective complications. RESULTS: The median (range) skin test scores preoperatively were: ranitidine group 8.5 (0-17), and control group 10 (0-19). The postoperative figures were 7 (0-28) and 4.5 (0-15.5) respectively. The corresponding numbers of positive antigens were 1 (0-4) and 3 (0-4) compared with 1 (0-5) and 1 (0-3). The changes in the scores did not seem to be influenced by blood transfusion, serum albumin concentration, age of the patient, or type of tumour. Two patients died in the ranitidine group (pulmonary embulus, n = 1, necrotising pancreatitis, n = 1) and there were 4 wound infections. There were no deaths in the control group, one intra-abdominal abscess, and 8 wound infections. Median hospital stay was similar, 10 (8-16) in the ranitidine group, and 11 (5-20) in the control group. CONCLUSION: Ranitidine had a beneficial effect on cell-mediated immunity as it seemed to prevent the usual postoperative reduction in reactivity, but there was no significant difference in the incidence of infective complications though it was lower in the ranitidine group. PMID- 7772629 TI - Effect of hepatocytes from normal or endotoxin treated animals on the production of tumour necrosis factor, interleukin-6, and prostaglandin-E2 by macrophages incubated in vitro with various fatty acids. AB - OBJECTIVE: To find out if the in vitro production of tumour necrosis factor (TNF), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) by macrophages (P3888D1) were influenced by the addition to the culture media of hepatocytes from normal guinea pigs and from guinea pigs after infusion with endotoxin with and without fatty acids. DESIGN: Laboratory experiment. SETTING: University hospital, United States MATERIAL: 12 male Hartley guinea pigs. MAIN OUTCOME MEASURES: Concentrations of TNF-alpha, IL-6, and PGE2. RESULTS: Hepatocytes inhibited the production of TNF by macrophages. Those from animals pretreated with endotoxin caused a large increase in the production of PGE2 and affected the production of IL-6 only in the presence of fatty acids. Fatty acids differed from each other in their effects on production of TNF-alpha and PGE2, but had no effect on the production of IL-6. CONCLUSION: These results support the concept that hepatocytes and macrophages may interact in vivo, and this interaction may be influenced both by fatty acids that arise from lipid metabolism and from endotoxin present during sepsis and translocation. PMID- 7772630 TI - Postoperative complications predict recurrence of Crohn's disease. AB - OBJECTIVE: To find out if any of six variables influenced the incidence and timing of recurrence after a first resection for Crohn's disease. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: 104 surviving patients of 106 who underwent a first resection for Crohn's disease between January 1976 and December 1990. MAIN OUTCOME MEASURES: Association between 6 variables (age, sex, site of diseased bowel, histological evidence of Crohn's disease, indication for operation, and incidence of postoperative complications) and incidence and time of recurrence after the first operation. RESULTS: Patients were followed up for a mean of 4.5 years (range 1-16). Presentation with acute perforation was associated with a higher incidence of recurrence (10/14 compared with 26/90), chi square 7.90, p = 0.005) and more than doubled the risk of that recurrence developing with six years (log rank chi square 11.7, p = 0.02); the same was true for development of a postoperative complication for which the corresponding figures were 14/26 compared with 22/78, chi square 4.59, p = 0.03, and log rank chi square 6.1, p = 0.01. CONCLUSION: These data support the hypothesis that there may be two types of Crohn's disease: an aggressive type that perforates and is prone to early relapse, and one that develops more slowly with an obstructive pattern, and which relapses less often and after a longer disease free interval. The development of postoperative complications is a previously unrecognised risk factor for early recurrence in Crohn's disease. PMID- 7772631 TI - Use of subcutaneous implantable infusion systems in neoplastic and AIDS patients requiring long-term venous access. AB - OBJECTIVE: To evaluate the life span and complication rates of totally implantable infusion devices in patients with short bowel syndrome and in immunocompromised patients with AIDS, lymphoma, and myeloma who required long term central venous access. DESIGN: Prospective open study. SETTING: University hospital, Italy. SUBJECTS: Group I - 5 patients with short bowel syndrome; group II - 11 patients with AIDS; and group III - 15 patients with lymphoma or multiple myeloma (1 of whom had 2 devices implanted). MAIN OUTCOME MEASURES: Duration of implantation and incidence of catheter-related complications. RESULTS: The mean duration/patient of the catheter was 422 days (range 20-1257) in group I; 104 days (range 43-262) in group II; and 415 days (range 62-1280) in group III. There were no catheter related complications in the patients in group I (short bowel syndrome). Of the 11 patients with AIDS (group II) 4 developed catheter related infections (0.32/100 catheter days), and 1 developed a thrombotic occlusion. All 5 catheters were removed (3 for infection). Of the 15 patients with lymphoma or myeloma who had 16 catheters implanted (group III), 1 patient developed 3 infective episodes (0.05/100 catheter days), 1 catheter migrated and 1 occluded. All 3 catheters were removed. CONCLUSION: Totally implantable infusion systems can safely be used for prolonged periods in immunocompromised patients, including those with AIDS if their life expectancy is reasonable. PMID- 7772632 TI - Papers presented at the Surgical Infection Society of Europe meeting. Varese, Italy, June 1993. PMID- 7772633 TI - Food deprivation increases bacterial translocation after non-lethal haemorrhage in rats. AB - OBJECTIVE: To investigate whether brief fasting before the induction of hypotension by non-lethal haemorrhage may induce translocation of enteric bacteria to mesenteric lymph nodes or blood in rats. DESIGN: Laboratory experiment. SETTING: University departments of surgery and microbiology, Sweden. MATERIAL: 39 Male Sprague-Dawley rats. INTERVENTIONS: 20 animals were fasted for 24 hours, all 39 then underwent controlled haemorrhage for 60 minutes that reduced the blood pressure to 55 mm Hg. MAIN OUTCOME MEASURES: Differences in blood loss, blood glucose concentrations, and packed cell volume; and aerobic cultures of mesenteric lymph nodes and blood. RESULTS: Fasted rats (n = 20) lost 2.3% of blood volume compared with 2.8% in fed rats (p < 0.001). Packed cell volume dropped by 11.3% in fasted rats and 16.5% in fed rats (p < 0.001). Glucose concentrations rose by 7.0 mmol/l in fasted rats compared with 21.0 mmol/l in fed rats (p < 0.001). Mesenteric lymph nodes contained enteric bacteria in 14/20 fasted rats compared with 6/19 fed rats (p < 0.05). In 4 fasted rats blood cultures grew pathogenic bacteria compared with no fed rats (p = 0.11). The number of bacteria found in mesenteric lymph nodes was significantly greater in fasted than in fed rats (p = 0.01). CONCLUSIONS: Brief fasting before hypotension caused by non-lethal haemorrhage was associated with significantly increased bacterial translocation compared with fed animals. Increases in blood glucose concentrations and plasma refill may have had a protective effect in fed rats. These experiments may be of clinical relevance as elective operations are usually preceded by overnight fasting. PMID- 7772634 TI - Early thoracoscopic debridement and drainage as definite treatment for pleural empyema. AB - OBJECTIVE: To report our experience with early thoracoscopic debridement and drainage in the treatment of pleural empyema in the fibrinopurulent or early organising phase. DESIGN: Prospective open study. SETTING: District hospital, Germany. SUBJECTS: 10 Patients operated on between August 1991 and April 1993. INTERVENTIONS: Double lumen intubation, followed by thoracoscopic opening of the empyema, evacuation of all pus under vision, debridement of the lung, irrigation of the thoracic cavity and insertion of a chest drain. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Cultures taken during the operation grew no pathogens in five cases; Streptococcus pneumoniae, and haemolytic streptococci (once in combination with Staphylococcus aureus), were cultured in two cases each; and Mycobacterium tuberculosis in one. Chest drains were removed a mean of 8.5 days after operation. All patients were well without signs of infection 1-21 months later, and in no case was conversion to open operation necessary. CONCLUSION: Early thoracoscopic debridement and drainage is a safe and effective alternative to open treatment of patients with pleural empyema in the fibrinopurulent or early organising phase. PMID- 7772635 TI - Adverse effect of abdominal operations on production of interferon-gamma. AB - OBJECTIVE: To assess the effects of abdominal operations on the production of cytokines as one of the mechanisms of postoperative immunosuppression. DESIGN: Prospective study. SETTING: University hospital, Belgium. SUBJECTS: 19 Selected patients who underwent operations for benign (n = 10) or malignant (n = 9) diseases. INTERVENTIONS: Whole blood was collected in heparinised tubes before operation and on postoperative days 1, 2, 3, 5, 7, and 9. After 1/10 dilution in culture medium the whole blood cells were stimulated with 5 micrograms/ml phytohaemagglutinin and 25 micrograms/ml lipopolysaccharide, and incubated at 37 degrees C in 5% carbon dioxide. Concentrations of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interleukin 6 (IL-6) were measured at 24 hours, and interferon-gamma and interleukin 2 (IL-2) were measured at 72 hours, with commercially available assays. OUTCOME MEASURES: Production of the monokines IL-1, TNF alpha, and IL-6, and of the lymphokines IL-2 and interferon-gamma, postoperatively. The monokines were expressed as a percentage of the preoperative values/monocyte, and the lymphokines as a percentage of preoperative values/lymphocyte. RESULTS: Production of IL-1 and TNF alpha, but not IL-6, decreased immediately after operation then returned to preoperative values. Production of IL-2 and interferon-gamma were significantly reduced immediately after operation, and that of interferon-gamma was still depressed on the ninth postoperative day. CONCLUSION: Cytokine production is altered after abdominal operations. The production of interferon-gamma may be a more sensitive indicator of altered immune response and vulnerability to infections and tumour growth than concentrations of other cytokines. PMID- 7772636 TI - Effect of different regimens of gut decontamination on bacterial translocation and mortality in experimental acute pancreatitis. AB - OBJECTIVE: To assess the effect of four regimens of antibiotics (compared with a control regimen of distilled water) given orally on gut decontamination, bacterial translocation, and mortality in acute necrotising pancreatitis in mice. DESIGN: Randomised experimental study. SETTING: University hospitals, USA and Italy. MATERIALS: 150 young Swiss Webster mice. INTERVENTION: All mice were fed a diet deficient in choline and supplemented with ethionine. They were then randomised to be given by gavage (36 hours after starting the diet): distilled water (controls, group 1); aztreonam along (group 2); neomycin, erythromycin, metronidazole (group 3); polymyxin B and amikacin (group 4); polymyxin B, amikacin, amphotericin B (group 5). 20 Mice in each group were treated for 10 days, and the remaining 10 in each group were killed after 3 days. MAIN OUTCOME MEASURES: Survival, and qualitative and quantitative cultures of the liver, lungs, pancreas and caecum. RESULTS: The best survival rate during the first 7 days was in group 5, but by day 10 there was no difference among the groups. All the antibiotic regimens reduced the number of bacteria in the caecum and all but aztreonam alone (group 2) reduced the rate of translocation of both Gram negative and Gram positive bacteria to all organs studied. Translocation of yeast occurred in those animals in groups 2, 3, and 4 in which there was overgrowth of fungi in the caecum. CONCLUSION: Gram negative and Gram positive organisms and fungi may have an important role in infective morbidity and mortality in acute pancreatitis, and selective decontamination with polymyxin B, amikacin, amphotericin B reduced the incidence of translocation related infections and early mortality in mice with acute necrotising pancreatitis. PMID- 7772637 TI - Luminal bacterial overgrowth and intestinal translocation in pigs given either cyclosporin A or 15-deoxyspergualin after small bowel transplantation. AB - OBJECTIVE: To examine the effects of two immunosuppressant regimens on composition of the bowel flora and rate of translocation after transplantation of the small bowel in pigs. DESIGN: Randomised controlled study. SETTING: University hospital, Italy. MATERIAL: 35 female Large White pigs. INTERVENTIONS: 9 Animals were not operated on (normal controls). 19 Animals underwent total orthotopic small bowel allotransplantation and were then randomised to receive: group A (n = 8) cyclosporin A 25 mg/kg subcutaneously and cephazolin 2 g intramuscularly daily; group B (n = 6) 15-deoxyspergualin (15-dos) 3 mg/kg for 7 days then 1.5 mg/kg, cephazolin 2 g intramuscularly daily for 4 days then selective intestinal decontamination with colistin 1.5 million U, tobramycin 100 mg, vancomycin 1 g, and nystatin 500,000 U daily; and group C (n = 5) cephazolin 2 g intramuscularly daily for 8 days. A further group (D, n = 7) underwent orthotopic autotransplantation and received the same antibiotic and selective decontamination regimens as group B. Animals in group C were killed on day 8, and the rest on day 29. MAIN OUTCOME MEASURES: Signs of rejection, graft versus host disease, luminal overgrowth, and evidence of translocation to mesenteric lymph nodes. RESULTS: All animals in group C, and 2 in group B, showed signs of acute rejection. There was a significant overgrowth of both aerobic and anaerobic bacteria in all 3 groups after allotransplantation compared with normal controls. Bacterial translocation was similar in autografted and allotransplanted animals. Mesenteric lymph nodes were colonised in 4/9 controls, 7/8 in group A, 4/4 in group B, 5/5 in group C, and 7/7 in group D. CONCLUSION: Neither cyclosporin A nor 15-dos prevented luminal overgrowth or bacterial translocation to mesenteric nodes up to one month after operation. The rate of translocation was similar in autotransplantation and allotransplantation, suggesting that non-immunological factors (for example, denervation and interruption of lymphatics) may have a role in these alterations. PMID- 7772638 TI - Tumour necrosis factor-alpha and interleukin-6: early indicators of bacterial infection after human orthotopic liver transplantation. AB - OBJECTIVE: To see if it was possible to predict the development of infection after liver transplantation from concentrations of endotoxin, tumour necrosis factor-alpha (TNF-alpha), or interleukin-6 (IL-6) in plasma. DESIGN: Prospective open study. SETTING: University hospital, Austria. SUBJECTS: 46 Consecutive patients who underwent liver transplantation for end stage liver disease, 1989 90. INTERVENTIONS: Samples of 4 ml blood were taken in endotoxin free tubes, and of 10 ml into heparinised tubes at the beginning of the operation, during hepatectomy, at the beginning and end of the anhepatic phase, 10 minutes after reperfusion, and at the end of the operation. MAIN OUTCOME MEASURES: Correlation between development of infections postoperatively and operative release of endotoxin, TNF-alpha, and IL-6. RESULTS: There was no correlation between development of postoperative infections and operative concentrations of endotoxin, and of TNF-alpha and IL-6 up to the end of the anhepatic phase. There was, however, a sixfold increase in TNF-alpha and IL-6 concentrations between the end of the anhepatic phase and the end of the operation in patients who subsequently developed infections (p = 0.01). CONCLUSION: The increase in the concentrations of these two cytokines in the blood after reperfusion of the transplanted liver seems to predict the development of subsequent bacterial infection. PMID- 7772639 TI - Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF-beta isoforms. AB - We have previously shown that TGF-beta 1 exerts a bifunctional effect on RAC proliferation. Added to quiescent cultures, it inhibits the entry of G0/G1 cells into S phase whereas in S phase synchronized populations, it stimulates the DNA replication rate with a delayed G2 + M phase and a subsequent transient increase of cell number. As TGF-beta 2 and beta 3 isoforms are also expressed in bone and cartilage tissues, it was of interest to study their effect on RAC proliferation, in comparison to that of TGF-beta 1. Using cell counting and tritiated thymidine incorporation, we found that all the TGF-beta s used here induced an increase of RAC proliferation rate occurring between 24 and 48 h of exposure. TGF-beta 2 appeared as the most efficient form as judged from the maximum of thymidine labelling. However, TGF-beta 3 induced an increase of cell number slightly higher than both TGF-beta 1 and TGF-beta 2 (+30% versus 20% for TGF-beta 1 and beta 2). TGF-beta 2 and beta 3 were able to stimulate the DNA replication rate as previously demonstrated for TGF-beta 1. However, the effect occurred later for TGF-beta 2 and beta 3 (12 h) than for TGF-beta 1 (6 h). This was confirmed by flow cytometric analysis of DNA content. In addition, immunodetection by flow cytometry demonstrated that all TGF-beta isoforms enhanced endogenous expression of TGF-beta-related peptides. The effect was shown to be associated with the cell cycle S phase and was greater for TGF-beta 3 than for TGF-beta 1 and beta 2. These findings suggest that TGF-beta s could act on RAC functions via autocrine and paracrine ways. Taken together, these data indicate that TGF-beta s may modulate proliferation of articular chondrocytes and therefore could play a role in the activation of these cells in the early stages of osteoarthritis. PMID- 7772640 TI - Streaming of labelled cells in the conjunctival epithelium. AB - This study examines epithelial cell streaming and turnover in normal rat bulbar conjunctiva. Twenty seven male adult random-bred Hebrew rats weighing between 250 300 g, were injected i.p. with [3H]-thymidine. Three rats were killed at various times, thereafter from 1 h to 28 days. The enucleated eyes were fixed in formalin, cut into 5 microns thick sections, dipped into liquid emulsion, exposed for three weeks and stained with haematoxylin and eosin. Conjunctival epithelium was scanned from the limbus and outward, using an ocular micrometer grid with 10 x 10 divisions. In each consecutive field the grid was positioned along the basement membrane which was defined as the x-axis. The y-axis extended from the basement membrane outward. The x, y coordinate of each nucleus with three grains or more and its grain content were recorded along the entire epithelium. Conjunctival epithelium is divided into two cell kinetic compartments: a progenitor (P), along the basal and supra basal layer, in which cells proliferate, and a non proliferating Q-compartment, in the layers above. One hour after labelling most of the labelled cells were in the basal and supra basal layers. From then onward labelled cells streamed along both axes. Their x velocity was 10.5 +/- 2.4 microns/day and the y-velocity 9.3 +/- 5.4 microns/day. Cells are eliminated at the epithelial surface which is the outer Q-compartment boundary. Basal cell turnover was estimated from grain count dilution curves. The time it takes for the grains in a cell to reach half of their initial value was 8.3 days. It is closely related to the cell's generation time. The present study demonstrates that conjunctival epithelium in the rat streams along two axes, x, and y: 1. The x-axis extends along the basal layer, from the limbus and outward. 2. The y-axis extends from the basal layer into the layers above it. Cells first stream along the x-direction and then turn y-ward. Since cells are ultimately exfoliated from the conjunctival surface, and since the conjunctiva maintains steady state, we propose that stem cells located in the limbus generate transitional cells that stream along the two axes. Macroscopically the limbus is circular, and the stem cells are situated around the cornea. Each stem cell and its streaming progeny can be viewed as a conjunctival epithelial unit. We propose that conjunctival and corneal epithelium, are the descendants of an uncommitted stem cell that generates two differentiation pathways, a corneal and a conjunctival. PMID- 7772641 TI - The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation. AB - Calcium supplementation decreases the incidence of colon cancer in animal models and may prevent colon cancer in man. Potential mechanisms include binding of mitogens and direct effects of calcium on colonic epithelial cells. In this study, the effects of extracellular calcium on epithelial cell growth and differentiation were studied in three colon carcinoma and two colonic adenoma cell lines. The characteristics studied included morphology, cell cycle kinetics, [Ca2+]IC (intracellular calcium concentration), proliferation, and expression of differentiation markers such as carcinoembryonic antigen (CEA) and alkaline phosphatase (AP). Sodium butyrate (NaB) and 1,25-dihydroxyvitamin D3 were used as controls in the latter three assays as these two agents are known differentiating agents. Alteration of [Ca+2]EC (extracellular calcium concentration) did not affect carcinoembryonic antigen (CEA) or alkaline phosphatase (AP) expression. NaB enhanced the expression of AP three-fold and CEA five-fold. This effect was augmented by increasing [Ca2+]EC. The exposure of cells to 1,25-(OH)2-Vitamin D3 increased CEA but not AP. [Ca2+]IC increased in response to 1,25-(OH)2-vitamin D3 and NaB but not with variation in [Ca2+]EC. Increased [Ca2+]EC inhibited proliferation of well-differentiated cells, but had no effect on poorly differentiated cells. Morphological studies showed that extracellular calcium was necessary for normal cell-cell interactions. These studies have demonstrated direct effects of calcium on colonic epithelial cells which may contribute to the protective effects of dietary calcium against colon cancer. Loss of responsiveness to the antiproliferative effects of [Ca2+]EC with de differentiation suggests that calcium supplementation may be most beneficial prior to the development of neoplastic changes in colonic epithelium. PMID- 7772642 TI - The World Federation of Societies of Biological Psychiatry. How it began: a historical note. PMID- 7772643 TI - Evidence against changes in corticotroph CRF receptors in depressed patients. AB - Previous studies by a number have investigators have documented a decreased adrenocortotropic hormone (ACTH) and beta-lipotropin/beta-endorphin (beta-End) response to ovine corticotropin-releasing factor (oCRF) in depressed patients. Since depressed patients demonstrate higher plasma cortisol concentrations at the time of oCRF challenge, it is difficult to determine if the decreased ACTH response is due to enhanced negative feedback of cortisol on ACTH release or an alteration in CRF receptors in depressed patients. To evaluate the response to oCRF in an "open feedback loop" system, we administered metyrapone 750 mg at 4 PM and 7:30 PM, followed by administration of oCRF 0.3 microgram/kg at 8 PM in 10 normal controls and 10 depressed patients. Administration of metyrapone at this time in the circadian rhythm clamped plasma cortisol concentrations to less than 2 micrograms/dl but did not result in rebound ACTH or beta-End secretion in control subjects. In control subjects, metyrapone administration produced a 85% blockade of the cortisol response as well as a 3-fold greater beta-End response compared to administration of the same dose of oCRF without metyrapone. The 10 depressed patients and their matched controls demonstrated identical beta-End responses (integrated response for controls = 291 +/- 61, for patients = 352 +/- 86) and cortisol responses (integrated response for controls = 187 +/- 38, for patients = 206 +/- 52) to oCRF following metyrapone pretreatment. These data confirm that corticotroph CRF receptors are normal in depressed patients, and that cortisol feedback plays an essential role in the abnormal ACTH and beta-End response to oCRF in depressed patients. PMID- 7772644 TI - Cortisol synthesis inhibition: a new treatment strategy for the clinical and endocrine manifestations of depression. AB - Evidence exists that oversecretion of cortisol may be responsible for the clinical manifestations and serotonergic abnormality in depressive illness. Using the cortisol synthesis inhibitor ketoconazole, we investigated the effects of directly lowering cortisol on the symptoms and the response of prolactin (PRL) to d-fenfluramine in eight patients suffering from major depression. Prolactin responses to d-fenfluramine were measured, and patients were treated with 400-600 mg of ketoconazole for 4 weeks, after which they were retested. Five patients treated with ketoconazole recovered from their depression, while the other three had decreases in their Hamilton Depression Rating Scale (HAMD) scores of < or = 50% and were deemed partial responders. Posttreatment prolactin responses to d fenfluramine were higher than pretreatment values. Ketoconazole normalizes the blunted prolactin responses to d-fenfluramine and may be an effective method by which to treat depression. This implies that hypercortisolemia may be responsible for the clinical features and serotonergic subsensitivity observed in depression. PMID- 7772645 TI - The psychotropic effects of inhibitors of steroid biosynthesis in depressed patients refractory to treatment. AB - Twenty patients, diagnosed as suffering from treatment-resistant major depression, were treated with one or more drugs that decrease corticosteroid biosynthesis. Nine were psychotic, 11 nonpsychotic. Seventeen completed the treatment (8 psychotic, 9 nonpsychotic); 13 responded (5 psychotic, 8 nonpsychotic; 11 responded completely (i.e., a drop in the Hamilton Depression Scale of at least 50%, to < or = 15), and 2 responded partially. The mean age of the responders (45.2 +/- 12.6 years) did not differ significantly from that of the nonresponders (48.7 +/- 12/3). Data were analyzed in the following categories; (1) the presence or absence of psychosis, (2) response or nonresponse to treatment, and (3) the drug(s) used (aminoglutethimide, ketoconazole, or a combination of either of these with metyrapone). The patients improved over time on the Hamilton Depression Scale independent of the medication used. Responders demonstrated improvement in mood, insomnia, anxiety, diurnal variation, paranoia and obsessive compulsiveness. Nonpsychotics responded better than psychotics. PMID- 7772646 TI - CRH challenge test in anxious depression. AB - Recently, renewed interest has developed in the concept of anxious depression. Using an operational definition of "anxious depression" based on the SADS interview, 25 patients with major depressive disorder were separated into anxious (n = 14) and nonanxious (n = 11) subtypes. These two patient groups and normal control subjects received an intravenous corticotropin-releasing hormone challenge test. Adrenocorticotropic hormone (ACTH) and cortisol responses were compared among the three groups. Patients with anxious depression had significant attenuation of ACTH response when compared to nonanxious patients and normal control subjects. PMID- 7772647 TI - Serotonin receptor binding in a colony model of chronic social stress. AB - Male rats housed in mixed-sex groups quickly established dominance hierarchies in which subordinates appeared severely stressed. Subordinate rats had elevated basal corticosterone (CORT) levels relative to dominants and individually housed controls. Several subordinates had blunted CORT responses to a novel stressor, leading to the classification of subordinates as either stress-responsive or nonresponsive. Binding to 5-HT1A receptors was reduced in stress-responsive subordinates compared to controls throughout hippocampus and dentate gyrus. Decreased binding was observed in nonresponsive subordinates only in CA3 of hippocampus. In addition, 5-HT1A binding was decreased in CA1, CA3, and CA4 in dominants compared to controls. Binding to 5-HT2 receptors was increased in parietal cortex in both responsive and nonresponsive subordinates compared to controls. No changes were observed in binding to 5-HT1B receptors. These results are discussed in the context of regulation of the serotonergic system by stress and glucocorticoids and possible relevance to the pathophysiology of depression. PMID- 7772648 TI - Antisaccades and smooth pursuit eye movements in schizophrenia. AB - Saccadic and smooth pursuit eye movements were recorded in schizophrenic patients, nonschizophrenic psychiatric patients, and normal controls. Both schizophrenic subjects and psychiatric controls demonstrated greater increases in error rates and greater delays in generating antisaccades than did normal controls. Schizophrenic patients with impaired smooth pursuit tracking showed greater increases in error rates in the antisaccade task than did schizophrenic patients with normal pursuit. Among psychiatric controls, increased errors on the antisaccade task were unrelated to pursuit performance. The small size of this group, however, reduces the power to detect a relation between smooth pursuit tracking and performance on the antisaccade task. Although most patients were receiving one or more medications, some of which can affect eye movements, medication state in this study did not account for differences we report in dependent variables. PMID- 7772649 TI - First month of neuroleptic treatment in schizophrenia: only partial normalization of the late positive components of visual ERP. AB - In a previous study we recorded visual event-related potentials (ERP) in drug naive schizophrenics during passive-attention and active-attention tasks. Patients, compared to normal controls, had much lower late positive components (LPC) in both sessions, but nearly normal LPC increase from passive to active task. The present sample consisted of drug-naive and drug-free patients who were tested before and during the first month of neuroleptic treatment. Neuroleptics initiated gradual amelioration of psychiatric symptoms expressed by reduced Brief Psychiatric Rating Scale (BPRS) scores. Schizophrenics compared to controls showed a session-related increase in LPC amplitude, but this process of LPC recovery was too minor to fully normalize the low LPC amplitudes in patients. Furthermore, the treatment either did not improve or even reduce the LPC reaction to the active-attention task. These findings indicate that normalization of low LPC in schizophrenia might require a long period of treatment, and that patients' reduced LPC reactivity to the task might be contributed, rather than treated, by neuroleptics. PMID- 7772650 TI - Specific IgA antibody increases in schizophrenia. AB - IgA antibody levels in serum were examined in two groups of schizophrenic patients. All were diagnosed according to DSM-III-R criteria. One group of 36 males and 12 females were compared to historical controls. The other group consisted of 13 males off drugs for at least 3 months; these were compared with age- and sex-matched controls. An increase in specific IgA antibodies was found. More schizophrenics than controls showed IgA antibody levels above the upper normal limit to gliadin, beta-lactoglobulin, and casein. PMID- 7772651 TI - Serotonergic responsivity in trichotillomania: neuroendrocrine effects of m chlorophenylpiperazine. PMID- 7772652 TI - Neurochemistry and paroxetine response in major depression. PMID- 7772653 TI - Attention and formal thought disorder in mixed and pure mania. PMID- 7772654 TI - [Effects of lumbar peridural anesthesia on tissue pO2 of the large intestine in man]. AB - AIM: The aim of this study was to investigate the effect of 15 ml bupivacaine 0.25%, given via an epidural catheter, on the tissue-PO2 of the colon wall in humans. METHODS: Nine patients were studied during elective colorectal surgery. The tissue-PO2 was measured by polarography, using a multiwire surface probe. RESULTS: There was no significant change in cardiac index and arterial oxygen delivery after the injection of bupivacaine. At the serosal side of the colon wall the tissue-PO2 increased from 34 to 51 mmHg after epidural bupivacaine, which is statistically significant. Spinal nerve block produces sympathetic denervation of the bowel with an increase of regional nutritive blood flow. CONCLUSION: It is concluded that epidural bupivacaine has a favourable effect on tissue oxygenation of the colon during colorectal surgery. PMID- 7772655 TI - [Indications for anesthesia?]. PMID- 7772656 TI - [Amniotic fluid embolism--a case report with positive outcome]. AB - While inducing delivery, shock occurred in a 23-year old primipara (41 weeks and 5 days of gestation). She showed symptoms of cyanosis, unconsciousness and asystoly. During cardiopulmonary resuscitation an emergency Caesarean section was performed. The resuscitation had to be continued for 1.5 hours and was followed by severe haemorrhage. Hysterectomy had to be performed, because the substitution of packed red blood cells, whole blood, fresh frozen plasma and other blood derivatives could not stop bleeding. Although the prognosis seemed to be very poor, mother and child survived without any physical damage or neurological deficit until now. Because of the clinical pattern we diagnosed an AFE syndrome (amniotic fluid embolism). PMID- 7772657 TI - [Central anticholinergic syndrome after propofol anesthesia]. AB - A 37-year old patient was anaesthetised twice within 4 weeks for surgery of a vertebral disc prolapse. The first anaesthesia was performed with volatile anaesthetics without any anomalies. After the second operation in total intravenous anaesthesia with propofol and alfentanil the excitatory form of a central anticholinergic syndrome occurred. The application of physostigmine resulted in an immediate and complete disappearance of the symptoms. PMID- 7772658 TI - The laryngeal mask airway--fixation, gags and stability. PMID- 7772659 TI - [Anesthesia in ambulatory surgery]. PMID- 7772660 TI - [Allergic and pseudo-allergic reactions in anesthesia. II: Symptoms, diagnosis, therapy, prevention]. AB - In this article we present the symptomatic features and discuss relevant diagnostic and therapeutic aspects of anaphylactoid reactions. In addition we give practical advice as to how to avoid and manage allergic or pseudoallergic reactions during anaesthesia. Measurements of serum tryptase-levels and of methylhistamine in urine have been introduced in clinical diagnostic routine. Skin tests and determination of specific antibodies are essential to identify responsible substances. Preventive measures like careful premedication, calm atmosphere, slow injection of drugs, the use of diluted solutions, and the use of drugs with a low potential for anaphylactoid reactions are important. Substances like inhalation anaesthetics, propofol, etomidate, ketamine, midazolam, fentanyl, alfentanil and bupivacain without epinephrine should be used. PMID- 7772661 TI - [Anesthesia for surgery in ambulatory patients: organizational aspects of the hospital physician]. AB - At first sight it seems impossible to put into practice the 1992 resolution of the German Federal Council recommending increased frequency of hospital based operative care for ambulatory patients and the duty to do so under full financial coverage. A detailed analysis of the current situation suggests that this may be possible even today--with some reservations regarding the infrastructure of the hospitals. Selection and preparation of the patient is a process in which the anaesthesiologist must play an important role. Delegation of this duty to the surgeon or the general practitioner is not permitted. The anaesthesiologist must have sufficient time, prior to the procedure, to meet the patient; meeting the patient for the first time a few minutes before induction of anaesthesia is unacceptable. Even if one concedes freedom of methods, one drug and one procedure should be avoided while caring for surgical ambulatory patients: this drug is succinylcholine, because of life-threatening hyperkaliaemia in children with occult myopathy and severe and frequent myalgia especially in ambulatory patients. The procedure not suitable in ambulatory patients is subarachnoidal analgesia--due to an unacceptably high percentage of headaches in young ambulatory patients. The postoperative care and observation must be delegated to especially qualified persons only--and these persons should not be distracted by duties outside the recovery area. The anaesthetist must--in addition--be available at all times without delay. Pain, nausea and emesis molest the ambulatory patient during the postoperative course to a particular extent. The anaesthesiologist must take care of these complaints--even if the patient is discharged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772662 TI - [Current status of ambulatory pediatric anesthesia]. AB - Anaesthesia in paediatric outpatients represents a multi-facetted challenge for the anaesthesiologist. Certain steps have to be taken to allow preoperative examination of the patient on an outpatient basis. Preoperative screening should identify patients whom it is preferable to treat as inpatients. During the preoperative visit, the patient must be prepared for anaesthesia, and the importance of preoperative fasting must be stressed. The anaesthetic technique used has to take into consideration the fact that the patient must be awake and alert in the early postoperative period. Adequate pain treatment is essential postoperatively. Prophylactic administration of antiemetic agents must be considered for special operations. Patients should also be discharged according to standardised guidelines. In this way, the risks involved in anaesthesia and surgery should not be higher for outpatients than they are for inpatients. PMID- 7772663 TI - [Behavior of intraocular pressure in anesthesia with isoflurane in comparison with propofol/alfentanil]. AB - AIM: To investigate the influence of isoflurane anaesthesia versus total intravenous anaesthesia with propofol/alfentanil on intraocular pressure (IOP). METHODS: 40 patients undergoing ophthalmic surgery were randomly allocated to two study groups. In group 1 (n = 20), anaesthesia was induced with thiopentone 4 mg/kg and alfentanil 15 micrograms/kg. Maintenance of anaesthesia was achieved with isoflurane 0.5-0.8 Vol.% and 70% nitrous oxide in oxygen. Patients in group 2 (n = 20) received propofol 1.5 mg/kg, which was followed by a continuous infusion of 6 mg/kg/h. In addition, alfentanil 15 micrograms/kg was administered, followed by a continuous infusion of 15 micrograms/kg/h. In both groups, endotracheal intubation was facilitated by succinylcholine 1 mg/kg, and further muscle relaxation was achieved with vecuronium 0.07 mg/kg. Measurements of IOP using an applanation tonometer were taken in each patient at 10 different time points. RESULTS: In both groups, there was a significant decrease in IOP after induction of anaesthesia. No significant differences in IOP occurred between groups, with patients in group 2 showing a trend towards lower IOP values. CONCLUSION: We conclude from our results that both anaesthetic techniques can be administered if increases in IOP have to be avoided. PMID- 7772664 TI - [Incidents, events and complications in the perioperative period in normal and malnurished patients--results of 23,056 patients]. AB - AIM: Prevalence of cardiovascular risk factors in anaesthetic patients and perioperative pitfalls, events and complications (PECs) in different nutritional states were examined. The results should contribute to a current project of the German Society of Anaesthesiology and Intensive Care, established for quality assurance. METHOD: Preoperative data (age, sex, defined preexisting diseases, nutritional state, grade of urgency and ASA-class) were integrated in an automatically readable paper record, as well as the perioperative interventions and events, type of anaesthesia, and kind of operation. The records were routinely in use for every patient. After control and correction the data were stored in a modern data base. Data of patients under 16 years of age and incomplete sets of data were excluded from analysis. MAIN RESULTS: From July 1, 1992 to December 31, 1993 23,056 anaesthesias were recorded, 5,852 (25.4%) of them with a total of 8,107 PECs. 17,255 patients had normal body weight and 23% of them PECs. 4,484 obese (but not extremely) patients had a PEC rate of 31.2%, 330 extremely obese patients had a PEC rate of 38.2%, 966 patients with underweight (but not extremely) had a PEC rate of 36.1% and 21 with extreme underweight had a PEC rate of 38.1%. Obese patients had a higher prevalence of preexisting cardiovascular disturbances (angina pectoris, myocardial infarction and hypertension) and tended to a higher incidence of perioperative hypertensive, bronchospastic and hypoxic events as well as more difficulties in application of regional anaesthesia. Young adult patients (16-39 years) had a PEC rate of 14% in case of normal nutritional state but of 20% in case of obesity. The incidence of respiratory PECs and of PECs of higher severity was almost double in obese young patients compared to normal weight patients of the same age. When preoperative cardiovascular disease was known there was little difference between the different states of nutrition in respect of perioperative PECs. CONCLUSIONS: Nutritional disorder is an important epidemiological factor in anaesthesia. Particularly in younger patients without defined preoperative cardiovascular disturbance but with obesity the anaesthesist may be surprised by a remarkable incidence of relevant problems during and immediately after anaesthesia. We should consider the possible phenomenon that we are underestimating the anaesthetic challenge in young obese patients in a "healthy" cardiovascular state. PMID- 7772665 TI - In vivo degradation and biocompatibility study of in vitro pre-degraded as polymerized polyactide particles. AB - The degradation of high molecular weight as-polymerized poly(L-lactide) (PLLA) is very slow; it takes more than 5.6 yr for total resorption. Moreover, the degradation products of as-polymerized PLLA bone plates, consisting of numerous stable particles of high crystallinity, are related with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that are anticipated to have comparable mechanical properties but a higher degradation rate and do not degrade into highly stable particles that can induce a subcutaneous swelling. On chemical grounds it can be expected that copolymerization of PLLA with 4% D-lactide (PLA96) or by modifying PLLA through cross-linking (CL-PLLA) will lead to less stable particles and a higher degradation rate. To evaluate the long-term suitability of these as-polymerized polymers, the biocompatibility of the degradation products should be studied. Considering the very slow degradation rate of as-polymerized PLLA, in vitro pre degradation at elevated temperatures was used to shorten the in vivo follow-up periods. In this study, the biocompatibility and degradation of as-polymerized PLLA, PLA96 and CL-PLLA were investigated by implanting pre-degraded particulate materials subcutaneously in rats. Animals were killed after a postoperative period varying from 3 to 80 wk. Light and electron microscopical analysis and quantitative measurements were performed. The histological response of all three pre-degraded materials showed a good similarity with in vivo implanted material. Pre-degraded PLLA induced a mild foreign body reaction and showed a slow degradation rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772666 TI - Subperiosteal behaviour of alginate and cellulose wound dressing materials. AB - A histological comparison was undertaken of the tissue response to a new sodium calcium alginate material (Kaltostat) and an oxidized regenerated cellulose wound dressing (Surgicel) when implanted between bone and periosteum in the jaws at intervals of up to 24 wk. Both biomaterials caused a foreign body reaction, persisting up to 12 wk after surgery. New bone formation occurred along the surface of the mandible in some specimens, but was not apparently related to the implants. It was concluded that the implantation of Kaltostat or Surgicel between bone and periosteum in the jaws caused a delay in wound healing, and had no effect on bone induction. PMID- 7772667 TI - Calcification and fatigue failure in a polyurethane heart value. AB - The prosthetic heart valves were fabricated from a polyurethane containing a 4,4' diphenylmethane diisocyanate hard segment, chain-extended with butanediol and with a polyether soft segment. The rate of calcification of these polyurethane heart valves was much slower in a dynamic in vitro test system than similar bioprosthetic heart valves. The calcified deposits were located exclusively at regions of material failure. Fourier transform infrared (FTIR) spectroscopy indicated the involvement of the polyether soft segments of the polymer directly in the calcification process. Calcification of polymer fractions also suggested that small molecular weight extractable components are accelerating factors in the calcification process. PMID- 7772668 TI - Attachment and proliferation of osteoblasts and fibroblasts on biomaterials for orthopaedic use. AB - Using a variety of cell types, cell attachment and growth was studied on prospective (polyethersulphone (PES) and polyetheretherketone) and currently used (titanium 318 alloy, cobalt chrome molybdenum alloy and ultra-high molecular weight polyethylene (UHMWPE)) orthopaedic biomaterials. Proliferation of fibroblasts and osteoblasts was measured using incorporation of tritiated thymidine into total DNA. Attachment of cells was assessed by indirect immunofluorescent labelling of vinculin, a component of the cell's focal adhesion plaque. The degree of cell attachment was quantified on the materials by determining the mean number of adhesion plaques and using an image analysis system to determine the mean total area of plaques per cell. Fibroblasts and osteoblasts responded differently to the materials tested. When grown on PES surfaces, rat tail fibroblasts synthesized significantly greater amounts of DNA than cells on all other surfaces, whilst fibroblasts on UHMWPE synthesized significantly less DNA than cells on all other materials. Interestingly, there was no significant difference between the amounts of DNA synthesized by osteoblasts grown on the various materials. Determination of the number of vinculin adhesion plaques per cell and the mean total area of the plaques per cell showed that the attachment of fibroblasts to UHMWPE was significantly reduced compared with other materials. In contrast there was no significant difference in the adhesion of osteoblasts to different materials. Scanning electron microscope (SEM) observations of cells on the materials correlated with the morphometric data. Cells with the greatest number and area of adhesion plaques were well spread and flattened whilst those with the least number of adhesion plaques were more rounded and less spread. PMID- 7772669 TI - Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces. AB - Poly(N-isopropylacrylamide) (PIPAAm), exhibiting a lower critical solution temperature (LCST) at 25 degrees C in physiological phosphate buffered saline solution (pH 7.4) and at 32 degrees C in pure water, was grafted onto the surfaces of commercial polystyrene cell culture dishes. This PIPAAm-grafted surface exhibited hydrophobic surface properties at temperatures over the LCST and hydrophilic surface properties below the LCST. Endothelial cells and hepatocytes attached and proliferated on PIPAAm-grafted surfaces at 37 degrees C, above the LCST. The cultured cells were readily detached from these surfaces by lowering the incubation temperature without the usual damage associated with trypsinization. In this case, the optimum temperature for cell detachment was 10 degrees C for hepatocytes and 20 degrees C for endothelial cells. Cell detachment was partially inhibited by sodium azide treatment, suggesting that cell metabolism directly affects cell detachment. Morphological changes of the adherent cells during cell detachment experiments indicated further involvement of active cellular metabolic processes. Cells detached from hydrophobic hydrophilic PIPAAm surfaces not only via reduced cell-surface interactions caused by the spontaneous hydration of grafted PIPAAm chains, but also by active cell morphological changes which were a function of cell metabolism. PMID- 7772671 TI - Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly(ortho esters). AB - Poly(ortho esters) prepared by the condensation of 1,2,6-hexanetriol and an alkyl orthoacetate are viscous, semisolid materials at room temperature that can be injected using a blunt needle. When tetracycline was incorporated into these materials, complete release occurred within about 24 hours, but when small amounts of Mg(OH)2 were incorporated into the polymer release could be extended to many weeks, and a loading of 0.5 wt% resulted in sustained release of about 10 days. When adhesion was tested using bovine teeth, cohesive failure of the pure polymer occurred at a force of about 392 mN cm-2 and cohesive failure of a polymer incorporating 10 wt% tetracycline and 1 wt% (Mg(OH)2 occurred at about 118 mN cm-2. The combination of injectability, dentoadhesiveness and ability to control accurately the release of incorporated antibiotics makes these materials promising candidates for bioerodible delivery systems useful in the treatment of periodontitis. Toxicological studies are currently in progress. PMID- 7772670 TI - Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. AB - The hydrolytic degradation of aliphatic polyesters derived from lactic and glycolic acids (PLA/GA polymers) has been previously shown to proceed heterogeneously in the case of large size devices, the rate of degradation being greater inside than at the surface. A qualitative model based on diffusion reaction phenomena was proposed which accounts for the formation of the more stable outer layer. However, this model also suggested that devices with dimensions smaller than the thickness of the outer layer should degrade less rapidly than larger ones. In an attempt to check this hypothesis, 15 x 10 x 2 mm compression moulded plates, millimetric beads and submillimetric microspheres and cast films, derived from the same batch of poly (DL-lactic acid) polymer were allowed to age comparatively in isoosmolar 0.13 M phosphate buffer, pH 7.4, at 37 degrees C. Ageing of the various devices was monitored by measuring water absorption, weight loss, L-lactic acid formation, pH and molar mass changes. As expected, large size plates and millimetric beads degraded heterogeneously and much faster than homogeneously degraded submillimetric films and particles. PMID- 7772672 TI - In vivo and in vitro elimination of aliphatic polyanhydrides. AB - The hydrolysis and elimination processes of biopolyanhydrides has been studied using a polymer series of linear aliphatic diacids. This polymer series degrade into their monomer counterparts at about the same rate but differ in the water solubility of their degradation products. Polymers based on natural diacids of the general structure -[OOC-(CH2)x-CO]n- where x is between 4 and 12 were implanted subcutaneously in rats and the elimination of the polymers from the implantation site was observed. The in vitro hydrolysis of this polymer series was studied by monitoring the weight loss, release of monomer degradation products and the content of anhydride bonds in the polymer as a function of time. A dependence was found between the monomer solubility and the rate of polymer elimination in both in vivo and in vitro. The elimination time for polymers based on soluble monomers (x = 4-8) was 7-14 days, while the polymers based on low monomer solubility (x = 10-12) were eliminated only after 8 weeks. The in vitro degradation of polyanhydrides in the presence of several common hydrolytic enzymes found around implants did not affect polymer degradation. All polymers were biocompatible and found to be useful as carriers for drug delivery. PMID- 7772673 TI - Microcapsules through polymer complexation. Part 3: Encapsulation and culture of human Burkitt lymphoma cells in vitro. AB - Methacrylic acid (MAA) based polyelectrolytes were complexed with protonated or quaternized dimethylaminoethyl methacrylate (DMAEMA) containing polyelectrolytes to form microcapsules in vitro. Anchorage independent human Burkitt lymphoma (Raji) cells were successfully cultured in the presence of dissolved MAA containing polymer. Capsule morphology was investigated by light microscopy and by scanning electron microscopy (SEM). Capsules based on quaternized DMAEMA containing polymer were found to be more stable than capsules containing protonated DMAEMA functionality. Raji cells were successfully encapsulated in both systems and divided to confluence; thereafter sufficient pressure was exerted to burst open the capsules. Cells released from these capsules appeared to suffer no discernible trauma and were successfully isolated and subcultured to confluence. PMID- 7772674 TI - Cytotoxicity and mutagenicity of Kevlar: an in vitro evaluation. AB - Toxicity and mutagenicity of Kevlar 49 (PPPT; poly-para-phenylene terephthalamide) was tested in six strains of Salmonella typhimurium (Ames test; TA97, TA98, TA100, TA102, TA1535, TA1537) with and without an external metabolic activation system (S9), as well as in a mammalian cell mutagenesis assay using V79 Chinese hamster cells. For the Ames test, liquid preincubation, which is considered particularly sensitive, was used. The cells were incubated for 24 h at a temperature of 37 degrees C either directly with Kevlar49 or with ethanol- or chloroform-extracted Kevlar49. The experiments were performed at least twice. The Ames test with six different Salmonella typhimurium strains featuring either base pair substitution or frameshift mutations revealed no cytotoxic or mutagenic activity of Kevlar49. In the mammalian cell mutagenesis assay, using 8-azaguanine (AG) as a selective agent, Kevlar49 was also devoid of cytotoxic or mutagenic activity. Both tests have to be regarded as an initial exploratory screening due to the chosen testing conditions and should be supplemented by tests at different temperatures. PMID- 7772675 TI - Enzymatic assay of hydroxybutyric acid monomer formation in poly(beta hydroxybutyrate) degradation studies. AB - A novel method for monitoring the degradation of poly(beta-hydroxybutyrate) based on the enzymatic assay of beta-hydroxybutyrate (HBA) monomers has been developed. The method is particularly applicable to forms of the polymer, such as fibre and microcapsules, for which conventional surface and gravimetric monitoring techniques are not readily applicable. The method involves the use of enzyme HBA dehydrogenase in a reaction that converts nicotinamide adenine dinucleotide (NAD) to its reduced form (NADH). The conversion is associated with an increase in light absorption at 340 nm which thus serves to indicate the concentration of HBA monomer in the sample. The application of the methodology to the degradation of poly(beta-hydroxybutyrate) gel spun fibres has been used to demonstrate its potential use as a quantitative monitoring technique in the study of the hydrolysis of this polymer. PMID- 7772676 TI - Nitric oxide in cardiovascular disorders. AB - Nitric oxide derived from the vascular endothelium and other cells of the cardiovascular system has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. Nitric oxide can be synthesised from L-arginine by any of three isoforms of nitric oxide synthase (NOS), and its interaction with prostacyclin, its proposed mechanisms of action and cytotoxicity are briefly reviewed in the context of cardiovascular function. Although nitric oxide can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Nitric oxide has important roles in the physiological regulation of local blood flow and blood pressure, especially during exercise and in response to shear stresses and other local factors in arterioles. Nitric oxide is also involved in neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilatation and inflammation associated with activation of sensory nerves. In pathological circumstances, excess nitric oxide produced by inducible NOS compromises circulatory function in septic shock, during transplant rejection, and during myocardial ischaemia and reperfusion injury. Immunosuppressant drugs like cyclosporin A inhibit the expression of NOS through complex intracellular intermediates. Disturbances in the activity of constitutive and inducible NOS in the artery wall accompany the development of atherosclerosis, vasospasm and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. Reversing the nitric oxide defect with therapeutic agents including angiotensin-converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease. PMID- 7772677 TI - Distribution of biglycan and its propeptide form in rat and bovine aortic tissue. AB - The matrix proteoglycan biglycan was identified in bovine and rat aortic tissue by Western blot analysis and by immunohistochemistry, using polyclonal antibodies raised against peptides of the propeptide and the hypervariable region of the rat biglycan core protein. Western blot analysis of proteoglycans isolated from bovine and rat aortas by ion exchange chromatography and treated with chondroitin ABC lyase, with antibody against propeptide, demonstrated core proteins with molecular weights ranging from 43,000 to 45,000 daltons. Similar results were obtained with Western blot studies using the peptide antibody to the hypervariable region of biglycan, except the antibody did not recognize the core protein of bovine biglycan. Location of biglycan within bovine and rat aortic tissue sections by immunoperoxidase histochemistry using the antibody raised against the propeptide revealed intense intracellular staining of medial myocytes and endothelial cells but no extracellular staining. In contrast, immunohistochemistry performed with the purified antibody to the hypervariable region revealed significant extracellular staining of the adventitia proximate to the media and of the endothelial lining but no intracellular staining of rat aortic tissue, with no observable staining of bovine aortic tissue. These data demonstrate that, in contrast to cultured smooth muscle cells, biglycan containing the propeptide is not secreted and deposited within the extracellular matrix by smooth muscle cells and endothelial cells from aortic tissue. PMID- 7772678 TI - Angiotensin-converting enzyme inhibition reduces diabetes-induced vascular hypertrophy: morphometric studies. AB - Angiotensin-converting enzyme (ACE) activity and vascular mass are both increased in the mesenteric arteries of diabetic rats. As vascular hypertrophy may result from smooth muscle growth following increased formation of angiotensin II, we have examined the histological nature of the increase in mesenteric arterial mass and the role of elevated ACE activity in diabetic vascular hypertrophy by administration of an ACE inhibitor (perindopril). Cross-sectional area of the media was measured in perfusion-fixed mesenteric vessels of diabetic rats 3 weeks after streptozotocin injection. The media was significantly larger (63%) in mesenteric vessels of diabetic rats compared to age-matched control animals. Medial hypertrophy in these vessels was not associated with increased blood pressure or plasma renin activity but there was evidence for increased hemodynamic load due to hyperphagia and intestinal enlargement. Increased mesenteric ACE activity was involved in this process as there was significant inhibition of medial hypertrophy by perindopril. Other markers of cardiovascular hypertrophy such as left ventricular weight and aortic medial area were less affected, but increased in the diabetic group when corrected for significant body weight effects, consistent with a systemic influence of diabetes on cardiovascular mass. These data provide new insights into the mechanisms of vascular complications of diabetes and may have implications for the use of ACE inhibitors in preventing or arresting diabetes-associated vascular pathology. PMID- 7772679 TI - Impaired endothelial relaxations induced by agonists and flow in spontaneously hypertensive rat compared to Wistar-Kyoto rat perfused coronary arteries. AB - The study was designed to compare the effects of agonists and flow on endothelial reactivity in perfused coronary arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. To this end, coronary arteries were cannulated at both ends using an arteriograph system. In the absence of flow and under an intraluminal pressure of 30 mm Hg, SHR arteries had larger internal diameters compared to those of WKY rats (275 +/- 10 vs. 239 +/- 7 microns, p < 0.01). In preparations preconstricted with serotonin HT, concentration-effect curves were constructed by adding acetylcholine or bradykinin in the bath. On the other hand, the effect of a stepwise increase in intraluminal flow (50-450 microliters/min) of physiological salt solution was observed. Agonist-induced dilations were significantly smaller in arteries of SHRs compared to those of WKY rats. Starting flow at the plateau of constriction led to dilations that were also weaker in SHR compared to WKY vessels: 27 +/- 6 vs. 61 +/- 3, p < 0.001, when expressed as percentage of maximal initial constrictions. The maximal dilation induced by flow in SHR arteries was obtained for a greater value of shear stress compared to that determined in WKY preparations: 81 +/- 6 vs. 60 +/- 4 dyn/cm2, p < 0.01. After endothelium destruction, flow-induced dilation was totally abolished in SHR arteries but only reduced in those of WKY rats. Subsequent additions of sodium nitroprusside induced complete dilations in vessels from both strains. The same protocol was performed in arteries submitted to a perfusion pressure of 90 mm Hg. In these conditions, impairments of agonist- and flow-induced dilations were also evidenced in SHR arteries. These results show that both the endothelium-dependent dilation induced by acetylcholine or bradykinin and the flow-induced dilation are impaired in coronary arteries of SHRs compared to WKY rats. These alterations appear to be due to a deterioration of endothelial cell function in the presence of a normal reactivity of the smooth muscle cells. PMID- 7772680 TI - Localization of dopamine receptors in the rabbit lung vasculature. AB - The localization of dopamine receptor subtypes in the rabbit pulmonary circulation was investigated by using combined radioligand binding and light microscope autoradiography techniques. Dopamine D1-like receptors, probably belonging to the dopamine D1 receptor subtype, were demonstrated in sections of rabbit lung using [3H]-SCH 23390 as a ligand. This site is located within the tunica intima and the tunica media of large intrapulmonary artery branches (diameter > 300 microns) as well as within the tunica media of medium-sized pulmonary artery branches (diameter between 100 and 300 microns). No [3H]-SCH 23390 binding sites were found in small-sized pulmonary artery branches (diameter < 100 microns) or in pulmonary veins. Dopamine D2-like receptors, probably belonging to the dopamine D2 receptor subtype, were demonstrated with radioligand binding techniques in sections of extrapulmonary arteries but not of lung using [3H]-spiroperidol as a ligand. Light microscope autoradiography revealed the localization of this site within the tunica adventitia of extrapulmonary arteries as well as of large- and medium-sized intrapulmonary artery branches. The different anatomical localization of dopamine D1- and D2-like receptors in the rabbit pulmonary vasculature suggests that these sites are involved in the modulation of pulmonary vascular tone by interacting with different receptors having endothelial, muscular and probably prejunctional localization. The functional significance of the uneven distribution of dopamine receptor subtypes throughout the pulmonary vascular bed should be clarified in future studies. PMID- 7772681 TI - [Sjogren's syndrome: current concept]. PMID- 7772682 TI - [Correlation between clinical and autopsy diagnoses at a general hospital]. AB - In the past years, the number of hospital clinical autopsies have significantly decreased, with the risk of loosing some of the functions of this procedure, among which the evaluation of the diagnostic accuracy, which has been considered as a health care quality index, stands out. In this paper, the consistency between clinical diagnosis and autopsies in a general hospital is studied, as well as its association to some potentially relevant factors. We review 91 autopsies performed in patients dying in the Service of Internal Medicine during a period of six years. Each case was classified though consensus among a clinician and a pathologist into: mayor clinicopathological discrepancy, minor discrepancy or complete consistency. The relationship between consistency and age, sex, average length of stay in the hospital and study period was analyzed. The 91 autopsies were performed on 64 men and 27 women. The mean age was 63 years and the average length of study in the hospital was 9.7 days. The global consistency was 71.4%. In 15 (16.5%) cases, a major discrepancy was observed and in 11 (12.1%), a minor discrepancy. No differences were observed in the degree of consistency with respect to age, sex, average length of stay and study period. Cardiovascular diseases showed the greatest proportion of major discrepancies at the expense of three cases of pulmonary thromboembolism. We conclude that the degree of concordance in this study is consistent with other studies and we discuss the relevance of clinical autopsies regarding several aspects of health care. PMID- 7772683 TI - [Carcinomatous lymphangitis. Clinical study of 10 cases]. AB - We analyze the clinical characteristics, the diagnostic criteria and the radiological aspects of 10 cases of Carcinomatous Lymphangitis. The quickly progressing exercise dyspnea and the constitutional syndrome were the most frequent symptoms. In nine patients, the tumor was previously unknown. The image methods (adbominal CAT and Echography) and the fibrobronchoscopic exam allowed a correct diagnosis. The most frequent neoplasia had a pulmonary origin and the most frequent histology was adenocarcinoma. The histological tests (bronchial and transbronchial biopsies) were more effective for the diagnosis than the cytological test (bronchoalveolar lavage, bronchoaspiration and bronchial brushing), although these were complemented. The radiology showed a reticulo linear pattern in all the cases. The finding of macroscopic disorders in the fibrobronchoscopy, the presence of a local infiltration or a node/mass image in the thoracic radiography were highly suggestive of primary pulmonary neoplasia. PMID- 7772684 TI - [Hospital mortality at the internal medicine service of a local hospital]. AB - We conducted a retrospective study of the hospital mortality in a service of Internal Medicine at the Hospital de Barbastro during the years 1991 and 1992, recording 97 deaths during 1991 and 87 during 1992, with a mortality rate of 6.7% and 6.6% respectively. The mean age was 77.2% +/- 9 years with a 93% > or = 65 years. The average length of stay of the dead patients was 8.9 days. Cardiovascular diseases were the most frequent cause of death (41.85%), followed by respiratory diseases (17.93%) and neoplasias (15.76%). CVA was the single most frequent disease (17.9%). Ten autopsies (5.4%) were performed. In 16 cases (8.6%), we obtained data suggesting iatrogenesis, which in 7 cases (3.8%) clearly contributed to the direct cause of death. PMID- 7772685 TI - [Hemangioma, the most frequent hepatic tumor. Diagnosis with dynamic CAT]. AB - The sensitivity, specificity and predictive values of dynamic CAT with contrast piston-stroke performed at a single cut are described for the diagnosis of hepatic hemangiomas. We analyzed the correlation between the findings obtained through dynamic CAT and those obtained through echography, PAAF, analytic and clinical study of the patients with suspicion of hepatic hemangioma. The following values were obtained: sensitivity 92.3%; specificity 50%; VPP 88.8%; VPN 60%; and global diagnostic affectivity 84.37%. According to these results, we think that dynamic CAT is a highly reliable test for the diagnosis of hepatic hemangiomas. PMID- 7772686 TI - [Digestive hemorrhage caused by duodenal ectopic pancreas and diffuse angiodysplasia of the colon]. AB - We present the case of a 79-years-old male with episodes of digestive bleeding in the form of melenas in which two pathological findings were observed as potential causes: ectopic pancreas in subpyloric position and diffuse colon angiodysplasia. The difficult management of the digestive bleeding when two lesions are associated as potential causes is stressed. PMID- 7772687 TI - [Acute poisoning caused by hydrogen sulphide: clinical features of 3 cases]. AB - We describe three cases of acute intoxication by hydrogen sulphide which were produced after remaining between 50 and 60 minutes inside a cellulose tank. The three patients had loss of conscience. One of the patients developed a persistent vegetative state; another patient recovered although with neurological post anoxic sequelas and the third case completely recovered one week after his hospitalization. The patients underwent symptomatic treatment and the environmental concentrations of hydrogen sulphide were measured at the site of the accident. Finally, the application of preventive measures is stressed. PMID- 7772688 TI - [S. pneumoniae sternoclavicular arthritis in a patient with HIV infection]. AB - HIV infection is a predisposing factor for pneumococcic infection. While pneumonia is the most frequent location, other locations (articular, meningeal, endocardiac, etc) have been less frequently described. Among the articular infections described in patients with HIV infection, the sternoclavicular affection is extremely rare and it usually develops in association with parenterally drug addiction, being Staphylococcus aureus and Pseudomonas aeruginosa the most frequently germs involved. We describe the first case of sternoclavicular arthritis by Streptococcus pneumoniae in a patient with HIV infection. In our case, the chronic hepatopathy associated to alcohol consumption is a predisposing factor related to the pneumococcic infection. Our case suggests the need to formally investigate the HIV infection in young patients with invasive pneumococcic infection. PMID- 7772689 TI - [Visceral leishmaniasis and AIDS. Report of 2 cases with cutaneous dissemination]. AB - The cutaneous affection in visceral leishmaniasis (VL) or Kala-azar, is well known although poorly documented. The coinfection by the human immunodeficiency virus (HIV) has resulted in the development of frequent atypical forms of VL, increasing the descriptions of cutaneous affection in its evolution. We present two cases of VL-HIV, stressing the location of Leishmania in cutaneous lesions and in apparently normal skin. We suggest the cutaneous biopsy as diagnostic procedure and criteria for the definition of VL-HIV as indicative of AIDS. PMID- 7772690 TI - [Neutrophilic dermatosis in ulcerative colitis occurring in advanced age]. AB - The Neutrophilic dermatosis (ND) is considered as an independent entity with diverse clinical manifestations among which there are: gangrenous pyoderma, nodous erythema, Sweets Syndrome, vesiculopustula eruptions associated to ulcerous colitis and intestinal short circuit syndrome with or without short circuit. Histologically, they are characterized by infiltration of polymorphonuclear neutrophils, generally at the dermic level, but also at the epidermic. They are usually associated to systemic diseases, especially to chronic intestinal inflammatory disease. Our aim was to describe two forms of clinical presentation of neutrophilic dermatosis: gangrenous pyoderma and vesiculopustula eruption, associated to ulcerous colitis starting at advances ages. PMID- 7772691 TI - [Infective esophagitis]. PMID- 7772692 TI - [Occupational asthma]. PMID- 7772693 TI - [Acute abdomen secondary to intestinal tuberculosis in a patient with HIV infection]. PMID- 7772694 TI - [Subacute infective endocarditis complicated with mitral abscess and severe mitral insufficiency]. PMID- 7772695 TI - [Prolonged febrile syndrome without apparent focus and Coxiella burnetti infection]. PMID- 7772696 TI - [Significant high levels of transaminases in a patient with choledocholithiasis]. PMID- 7772697 TI - [Appetite increase and weight gain following treatment with megestrol acetate in patients with advanced cancer]. PMID- 7772698 TI - [Brucellar splenic abscess]. PMID- 7772699 TI - [Round pneumonia mimicking solitary lung nodule]. PMID- 7772700 TI - Preferential adsorption of cationic anti-DNA antibodies with immobilized polyanionic compounds, dextran sulfate. AB - It has been shown that cationic anti-DNA antibodies have nephritogenic potential in murine models of lupus nephritis. More recently, we have reported that there is a close relationship between the presence of circulating cationic anti-DNA antibodies and the development of lupus nephritis in humans, and that the cationic anti-DNA antibodies bind to heparan sulfate, a major glycosaminoglycan in glomerular basement membrane, much better than neutral anti-DNA antibodies. This suggests that cationic anti-DNA antibodies of the IgG class may be responsible for development of nephritis in vivo in patients with systemic lupus erythematosus. In this study, we first studied reactivity of anti-DNA antibodies with a panel of glycosaminoglycans in vitro using ELISA methods, and found that anti-DNA antibodies cross-react with dextran sulfate, hyaluronic acid and chrondroitin sulfate. The reactivity and selectivity of dextran sulfate with anti DNA antibodies was confirmed by in vitro immunoadsorption of the patient's sera with dextran sulfate-fixed column; incubation of auto-antibody-positive sera with dextran sulfate cellulose column removed anti-DNA, but not anti-RNP, anti-Sm, anti-SSA and anti-SSB antibodies from the sera in vitro. Of note is that dextran sulfate cellulose column absorbed exclusively, if not all, cationic anti-DNA antibodies in their sera. Nonspecific binding of total immunoglobulins as well as total proteins to the column was marginal. It has been suggested that cationic anti-DNA antibodies in sera of patients with refractory lupus nephritis could be efficiently removed by apheresis using dextran sulfate column. PMID- 7772702 TI - Cryptic antiphospholipid autoantibodies and serum co-inhibitors. PMID- 7772701 TI - Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes. AB - Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non labelled recombinant human GAD65 (rhGAD65). GAD67 antibodies (GAD67Ab) were similarly analyzed but without antigen competition. In 73 Japanese diabetic patients, GAD65Ab were found in 11/16 (69%) of patients with short-duration (less than 5 yrs) IDDM, 6/23 (26%) with long-duration (5 or more yrs) IDDM and 10/20 (50%) with slowly progressive diabetes. High GAD65Ab levels were associated with concomitant autoimmune diseases (p = 0.021). GAD67Ab were found in 4/16 (25%) of patients with short-duration IDDM, 3/23 (13%) with long-duration IDDM and 2/20 (10%) with slowly progressive diabetes. In 14 non-insulin dependent diabetic (NIDDM) patients, GAD65Ab and GAD67Ab were not found (0/14) and 1/50 (2%) healthy controls were positive in either assay. Among the GAD67Ab-positive samples, 8/9 (88%) were also high level GAD65Ab positive, 7/9 (77%) were displaced by an excess of rhGAD65 and the antibody levels correlated (r2 = 0.573; p = 0.003). Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67. PMID- 7772703 TI - Whither the anergic B-cell? AB - The kinetics of potentially autoreactive B-cells were investigated in a double transgenic model of self-tolerance. Two types of transgenic mice were created for this purpose. In the first the great majority of B-cells expressed the rearranged heavy and light chain genes encoding a high affinity receptor for hen egg lysozyme (HEL), while the second type expressed HEL in either soluble (sHEL) or membrane-bound (mHEL) form. Double-transgenic (Dbl-Tg) mice were produced either by mating the two types of founders or by transferring bone marrow cells from Ig transgenic (Ig-Tg) donors into irradiated HEL-Tg recipients. The lifespan of B cells from the Dbl-Tg mice was measured by oral loading with the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU) for periods varying from three days to six weeks. Experiments in various combinations of Dbl-Tg mice revealed a three tiered hierarchy of B-cell unresponsiveness, each level of which was characterised by a different B-cell lifespan. Exposure to mHEL led to rapid deletion of B-cells at an immature stage in their development with a median lifespan of approximately 15 hours. B-cells exposed to sHEL above a critical tolerogenic threshold were not deleted in the bone marrow but migrated to the spleen in an anergic state where they died within three days. If the receptor occupancy of sHEL was below the tolerogenic threshold, B-cells were neither deleted nor rendered anergic (ie were "indifferent") and had a normal median lifespan of four to five weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772704 TI - Nerve growth factor and autoimmune diseases. AB - The initiation of a humoral immune response to a foreign antigen is a complex biologic process involving the interaction of many cell types and their secreted products. Autoimmune diseases, which are characterized by an abnormal activation of the immune system, probably result from the failure of normal self-tolerance mechanisms. The etiology of such illnesses, however, is far from being understood. While there have been extensive studies on the participation of the immune and endocrine systems in autoimmune diseases, few have dealt with nervous system-mediated immunoregulation in such situations. Evidence continues to grow suggesting that nerve growth factor (NGF), first identified for its activity in promoting the growth and differentiation of sensory and sympathetic neurons, may exert a modulatory role on neuroimmunoendocrine functions of vital importance in the regulation of homeostatic processes. Newly detected NGF-responsive cells belong to the hemopoietic-immune system and to populations in the brain involved in neuroendocrine functions. NGF levels are elevated in a number of autoimmune states, along with increased accumulation of mast cells. NGF and mast cells both appear to be involved in neuroimmune interactions and tissue inflammation. Moreover, mast cells themselves synthesize, store, and release NGF, proposing that alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature. This review focuses on these cellular events and presents a working model which attempts to explain the close interrelationships of the neuroendocrinoimmune triade via a modulatory action of NGF. PMID- 7772705 TI - Autoantibodies against GAD65 rather than GAD67 precede the onset of type 1 diabetes. AB - The enzyme glutamate decarboxylase (GAD) is considered one of the major Beta cell antigens in Type 1 diabetes mellitus. The GAD autoantibody (GAD-AAb) prevalence in newly diagnosed Type 1 diabetic patients has been described up to 80%, depending on the detection method used. The aim of this study was to evaluate a simple, specific, and sensitive radioimmunoassay (RIA) method for detection of AAb against both isoforms of the enzyme, GAD65 and GAD67, in a cross-sectional study using sera from newly diagnosed Type 1 diabetic patients and in a longitudinal study using sera from prediabetic patients and individuals at risk of developing the disease. The 125I-labelled full-length human recombinant proteins of GAD65 and GAD67 expressed in SF9 cells were used as the antigen source. The prevalence of GAD65-AAb in newly diagnosed Type 1 diabetic patients was found to be 73% (112/153), in contrast to 19% (14/72) of GAD67-AAb. Only one patient produced AAb restricted to GAD67. Furthermore, GAD65-AAb could also be detected in 73% (11/15) of prediabetic patients (up to 122 months before clinical manifestation of the disease), whereas only 27% (4/15) of them were positive for GAD67-AAb. In the group at risk of developing Type 1 diabetes, these prevalences were 77% (10/13) and 46% (6/13), respectively. In all GAD67-AAb-positive patients investigated in the longitudinal study, AAb to GAD65 were detectable. In 47% of patients positive for both GAD65-AAb and ICA, the GAD65-AAb appeared by up to 46 months before the occurrence of ICA was detected. The data illustrated that GAD65 is the main immunogenic isoform of the enzyme in the preclinical and clinical stages. The RIA detecting AAb against this isoform may facilitate the screening for individuals at risk of developing the disease. PMID- 7772706 TI - Enhanced transcription of the gene encoding the SmN autoantigen in patients with systemic lupus erythematosus does not result in enhanced levels of the SmN protein. AB - The SmN, protein is closely related to the constitutively expressed SmB and SmB' autoantigens and can also act as a target for human autoimmune sera. In contrast to the single gene encoding SmB and SmB' which is expressed in all tissues, the distinct gene encoding SmN is expressed at high levels only in brain and heart tissue. We show that the SmN gene is transcribed at significantly elevated levels in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to normal controls. In contrast no significant elevation in transcription of the genes encoding SmB/B' or the U1-associated 70kD RNP autoantigen is observed in these patients. The elevation in SmN gene transcription in patient PBMCs does not result however, in enhanced levels of the SmN protein in the PBMCs of these patients. The significance of transcriptional and post-transcriptional processes in regulating the expression in SLE patients of SmN and other autoantigens is discussed. PMID- 7772707 TI - Complement-mediated cytotoxic activity of anti-heart antibodies present in the sera of patients with dilated cardiomyopathy. AB - A microcytotoxicity assay has been used to determine the cytotoxic activity of anti-heart antibodies which we have previously shown to be present with greater frequencies and reactivities in patients with dilated cardiomyopathy (DCM) than in patients with ischaemic heart disease (IHD). Serum samples from 45 patients with DCM and 43 patients with IHD were screened against W1, a transformed human fetal cardiac cell line and also against EA.hy 926, an endothelial and IBR3, a fibroblast cell line. In the presence of complement, sera from 28 (62%) DCM patients showed killing of the W1 cell line as compared to sera from 13 (30%) of IHD patients (p < 0.005) and 3 (15%) of normal individuals. In contrast, only 1 patient with DCM showed killing of the endothelial cell line and 1 patient with IHD showed killing of the fibroblast cell line. These results provide evidence for a complement-dependent, antibody-mediated mechanism of damage to cardiac myocytes which may contribute to the pathogenesis of DCM. PMID- 7772708 TI - [The temperature dynamics during the healing processing of a surgical wound]. AB - Using biomechanical principles, the qualitative occurrences in the wound were quantified. On the basis of the empirical knowledge that the wound, from its inception to healing, is warmer than its surroundings, we presumed that there was a certain regularity in the course of temperature values of the wound during primary healing. For measuring the temperature of the wound and its surroundings an electric thermometer of the ELLAB type was used. First, the temperature of the skin in the epigastric region in 30 healthy examinees, who were due to undergo a gall-bladder concrements operation was determined. The temperatures were measured within a traced dotted network. After the operation, in the same examinees, the temperatures were registered proximal to the wound and in its closer surroundings throughout the first eight post-operative days. Statistically evaluated the results showed that the temperature of the wound and of its surroundings, measured after operation, was higher than prior to operation. The temperature of the wound gradually rises up to the third post-operative day, and then gradually falls from the fourth post-operative day. This course of temperature is explained in part by the biological occurrences in the wound. The inflammatory reaction as a consequence of damage to the tissue is responsible for the initial increase of wound temperature. It lasts a limited time and has a limited intensity. This could be proved by histological preparations of the wound. The persistence of increased temperature after the third post-operative day is a sign of disturbed healing and predicts infection and secondary healing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772709 TI - [An optimized filter system for eliminating 50 Hz interference from high resolution ECG]. AB - A 50/60 Hz notch filter system was designed to eliminate powerline interferences from the high-resolution ECG. This special filter causes only minimal distortions of the power spectra and thus permits us to filter high-resolution ECG's without any appreciable changes in the frequency distribution of the original signal. Since the filter is based on an integer coefficient filter technique, the calculation time is relatively short, and the programming effort comparatively low. Three different automatically selected transfer functions ensure that an optimal filtered signal is obtained despite variations in the value of the interference. PMID- 7772710 TI - [Effect of the manufacturing process on creep and wear properties of UHMWPE (ultra-high molecular weight polyethylene)]. AB - The creep and wear behaviour of pressed UHMWPE and extruded UHMWPE was compared, taking Chirulen and extruded UHMWPE of the Lennite type as examples. Using the ring-on-disc test, the wear and deformation volumes per 360,000 cycles were determined. The static tests were performed at surface pressures of 5.62 MPa and 9.37 MPa, while the test duration was 41.86 and 100 hours, respectively. The surface pressures result from the axial forces of 900 N and 1500 N, respectively, and a ring surface analogous to the DIN 58,835 and ISO 6474 standards. Between conventionally pressed and the extruded UHMWPE material differences of up to 350% in the sums of wear and deformation were found. It was noted that already at low surface pressures the extruded UHMWPE is more susceptible to creep deformation than is the conventionally pressed material, and that this effect dramatically increases at high surface pressures. PMID- 7772712 TI - [Osseointegration of titanium test bodies of different surface properties in metaphyseal bone sites of the dog--a biomechanical and histological analysis]. AB - The alternative to the anchoring of an endoprosthesis by means of cement is the biological fixation by an ingrowth of bone into the implant surface (osseointegration). We examined the implant fixation properties of titanium experimental devices with 3 different surface structures after press-fit implantation into the bony bed of 12 dogs. One third of the 48 implants had a micro-structured surface roughened by grit-blasting, one third a roughened surface with an additional macro-groove structure (combination surface), and the remaining third a porous hydroxyapatite (HA) coating. Twelve weeks after implantation the bony ingrowth was evaluated biomechanically by measuring the force required to pull out the implant from the surrounding bone and histologically by morphometric assessment of microradiographs. In the pull-out experiment the shearing forces were significantly lower (p < 0.01) in the devices with a roughened surface in comparison to the devices with a micro- and macro structured surface and the HA surface. Thus, there was no significant difference between the forces required to pull out the devices with the porous HA surface and those with the combination surface. The histomorphometric assessment of bone density in the immediate vicinity of the implant and the extent of the direct contact surface of the bone implant resulted in no significant difference in all 3 groups. We did not find an interposing layer of fibrous tissue at the interface. We can demonstrate that roughening of the surface in combination with a groove structure creates a better bond between implant and bone than a roughening alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772713 TI - 4th International Conference on Human Antibodies and Hybridomas. Amsterdam, The Netherlands, 26-28 April 1995. Abstracts. PMID- 7772711 TI - [A CAE (computer aided engineering) approach to dynamic whole body modeling--the forces iin the lumbar spine in asymmetrical lifting]. AB - Biomechanical models of the human body play an important role in the analysis of the mechanical loading of the musculo-skeletal system. The whole-body model presented in this paper is based on a CAE (Computer Aided Engineering) program that permits the dynamic simulation of complex systems of rigid bodies. The model we developed on this basis consisted of 19 segments and 18 joints. The experimental data are derived from the 3D motion analysis system VICON, which is provided with 5 cameras, a force-plate and a 10-channel EMG recorder. The kinematic data are fed into the simulator after first being processed in a special manner to generate drivers for joint angles. The model was first used to calculate the compression forces generated within the lumbar spine during the asymmetric lifting and putting down of a 15 kg stone. The quasistatic calculation shows a dynamic contribution to the compression forces generated during the lifting of 11%. Increasing or decreasing the inertial moments of the segments by the factor 2 had an effect of less than 1% with the identical movement. PMID- 7772714 TI - Effect of insulin on the incorporation of 3H-inositol into the inositol phospholipids (PI, PIP, PIP2) and glycosyl-phosphatidylinositols (GPIs) of tetrahymena pyriformis. AB - The unicellular tetrahymena contains inositol phospholipids (PI, PIP, PIP2) and GPIs. Treatment with 10(-5) M insulin decreases the total 3H-inositol incorporation and incorporation into PI. 24 h after 10(-6) M insulin treatment there is an elevation of these parameters. Second treatment with 10(-6) M insulin doubles and 10(-5) M decreases these levels. This means that the effect on phosphoinositide turnover by insulin in Tetrahymena is rather concentration dependent. Inositol incorporation into GPIs is also influenced by insulin. PMID- 7772715 TI - Different secretory actions of pancreastatin in bovine and human parathyroid cells. AB - Chromogranin A is an acidic protein that is costored and cosecreted with parathyroid hormone (PTH) from parathyroid cells. Pancreastatin (PST), is derived from chromogranin A, and inhibits secretion from several endocrine/neuroendocrine tissues. Effects of different pancreastatin peptides were investigated on dispersed cells from bovine and human parathyroid glands. Bovine PST(1-47) and bovine PST(32-47) inhibited PTH release from bovine cells in a dose-dependent manner. The former peptide was more potent and suppressed the secretion at 1-100 nM. This inhibition was evident in 0.5 and 1.25 mM, but not in 3.0 mM external Ca2+. Both peptides failed to alter the concentration of cytoplasmic Ca2+ ([Ca2+]i) of bovine cells. Human PST(1-52) and PST(34-52) did not affect PTH release or [Ca2+]i of parathyroid cells from patients with hyperparathyroidism, nor [Ca2+]i of normal human parathyroid cells. Furthermore, bovine PST(1-47) and bovine PST(32-47) failed to alter the secretion of abnormal human parathyroid cells. The study indicates that PST exerts secretory inhibition on bovine but not human parathyroid cells, and that this action does not involve alterations of [Ca2+]i. PMID- 7772716 TI - Interaction of hypothalamic Na,K-ATPase inhibitor with isolated human peripheral blood mononuclear cells. AB - A ligand for the digitalis receptor located on the membrane-embedded Na,K-ATPase (NKA; EC 3.6.1.37) has been isolated from bovine hypothalamus (hypothalamic inhibitory factor; HIF) and identified as isomeric ouabain (Tymiak et al., 1993, Proc. Natl. Acad. Sci. 90: 8189-8193). In analogy to cardioactive steroids (CS) derived from plants or from toad, HIF inhibits the Na/K-exchange process and the ATPase activity of isolated Na,K-ATPase although by a different molecular action mechanism. In the present work we show that, as plant-derived ouabain, HIF inhibits 86Rb-uptake by isolated human lymphocytes with an IC50 of about 20 nM; above this concentration HIF reduces cell viability in contrast to ouabain. The decrease in cell viability by excess HIF is accompanied by discrete morphological alterations (mitochondrial swelling) visible by transmission electron microscopy of ultra-thin sectioned peripheral blood mononuclear cells. Taken together the results show that the hypothalamic NKA inhibitor blocks NKA of isolated human lymphocytes with high potency at nanomolar concentrations without toxicity; concentrations exceeding the ones required to block 86Rb-uptake reduce cell viability, probably due to leak formation across the NKA molecule. Thus, lymphocytes constitute a potential target for HIF action and by their altered NKA status a possible messenger between the nervous and the immune system. PMID- 7772717 TI - Treatment of cultured pancreatic B-cells with streptozotocin induces cell death by apoptosis. AB - Treatment of cultured pancreatic B-cells (HIT-T15 and RINm5F) with the diabetogenic drug streptozotocin resulted in a significant increase in the number of cells that became detached from the substrate during a subsequent culture period. Examination of the detached cells by fluorescence microscopy after staining with acridine orange or by electron microscopy revealed evidence of chromatin condensation and margination. Isolation and fractionation of DNA from these cells revealed a pattern of oligonucleosomal fragmentation that was not evident in untreated cells. All of these features are characteristic of entry of the cells into apoptosis and the results suggest that the diabetogenic action of streptozotocin involves induction of apoptosis in pancreatic B-cells. PMID- 7772718 TI - Peptide T from human immunodeficiency virus does not interact with VIP receptor effector system in immunocompetent cells of rat and mouse. AB - Human immunodeficiency virus (HIV) infection is initiated by attachment of the virus to specific target cells. An octapeptide sequence contained within the envelope of HIV, peptide T, mediates the viral binding. Since there is an appreciable structural similarity between peptide T and an eight amino acid sequence of VIP, it is interesting to investigate the interaction of peptide T with the VIP receptor-effector system of immunocompetent cells from both rat and mouse. In this paper, we show the lack of interaction between peptide T and VIP receptor-effector system in peripheral blood lymphocytes, spleen lymphocytes and macrophages of rat and in macrophages of mouse. These results do not support the hypothesis that HIV through peptide T may interact with the VIP receptor-effector system present in immunocompetent cells. PMID- 7772719 TI - Dynamic behavior in glycolytic oscillations with phase shifts. AB - Practically all of the studies of glycolytic oscillations in homogeneous spatial mediums have been performed through the construction of systems of ordinary differential equations and the search for their solutions. In this kind of modelling, the system dynamic behavior is considered to depend only on the values adopted by the parameters related to the dependent variables. In the present work, the modeling of a biochemical system through a system of functional differential equations with delay allows us to analyse the consequences that the variations in the parametric values linked to the independent variable (time) have upon the integral solutions of the system. In our model, the delays correspond with phase shifts in the initial functions for two dependent variables. The results of our researches show that when a instability-generating multienzymatic mechanism suffers variations of the delay time in any of its variables, a wide range of different dynamic responses can be produced. Our work is presented as an enlargement on the dynamic study of biochemical oscillations in general and, particularly, the glycolytic oscillations, under the consideration of the existence of variations in the phase shifts during the oscillations of metabolites involved in the studied reactive processes. PMID- 7772720 TI - Turing structures in a system with regulated gap-junctions. AB - In two coupled cells, each containing a bisubstrate-kinetics reaction system, the two substrates can cross the membranes through gap-junction protein channels (gating). Passing through the gap-junctions is controlled by one of the substrates, thus resulting in non-linear diffusion. Linear stability analysis gives the conditions, under which the symmetric fixpoint becomes unstable, leading to spatial asymmetry (Turing structures). The implications for morphogenesis are discussed. PMID- 7772721 TI - VIR: a computational tool for analysis of immunoglobulin sequences. AB - In this paper a microcomputer software named VIR (Variable domains of the Immune Receptors) is reported. This package can be used in sequence studies of immunoglobulin variable domains. The main features of the VIR software in the sequences management are: (1) ease of information recovery/extraction from amino acid sequences; and (2) its capability to obtain multiple sequence alignments with predefined characteristics (i.e. specie and/or specificity). As an analytical tool, the VIR package employs such multiple sequence alignments to compute: (1) tables showing amino acid frequencies; (2) three variability indexes; (3) identity matrices; (4) random samples; and (5) sequences with possible canonical structures. Thus the software reported here is proposed as a useful tool to carry out detailed studies of immunoglobulin variable domains. PMID- 7772722 TI - Global logic resulting from disequilibration process. AB - Describing a system in which internal detection or observation proceeds at a finite velocity is always destined to end up with a form of self-contradiction. For any formal language, for such a description, we must assume that the velocity of observation propagation or VOP be infinity. In the present paper, we propose a self-referential scheme intended for formally describing a system exhibiting the process of disequilibration propagating at a finite VOP, and find that a global logic can emerge from local disequilibration. Conservative cellular automata of Margolus type, for instance, enable disequilibration to be replaced by such a process that the number of particles is not conserved globally while appearing to be conserved by local observers. One cannot determine local rules universally. Nevertheless, global logic emerges as a result of the dynamics of a one-to-many type mapping. This is a fundamental aspect of natural languages or communication relevant to natural life and intelligence. PMID- 7772723 TI - Photosynthetic oscillations and the interdependence of photophosphorylation and electron transport as studied by a mathematical model. AB - A simple mathematical model of photosynthetic carbon metabolism as driven by ATP and NADPH has been formulated to analyse photosynthetic oscillations. Two essential assumptions of this model are: (i) reduction of 3-phosphoglycerate to triosephosphate in the Clavin cycle is limited by ATP, not by NADPH, and (ii) photophosphorylation is affected by the availability of both ADP and NADP, while electron transport is limited by NADP only. The model produces oscillations of observed damping and period in ATP and NADP concentrations which are about 180 degrees out of phase, while three alternative proposals regarding coupling of electron transport and photophosphorylation do not produce oscillatory model solutions. The phases of ATP and NADPH are in reasonable agreement with the available experimental data. The model (which assumes that redox control of photophosphorylation is part of the oscillatory mechanism) is compared with an alternative proposal (that oscillations are due to interdependence of turnover of adenylates and Calvin cycle intermediates). From the similarity of the mathematical structures of both models it is inviting to speculate that both models are partial aspects of 'the oscillatory mechanism'. PMID- 7772724 TI - Community treatment of HIV-1: initial stage and asymptotic dynamics. AB - Treatment with antiviral drugs (zidovudine and ddI) has been reported to delay progression to AIDS, and may even possibly lower the infectiousness of the infectives. However, its effect on the community level is still uncertain. The latter is important since a successful community treatment program must meet both public health and individual health goals. Our study will focus on the effect of a community-wide treatment program initiated at the early stages of the disease as well as the long-term effect of the program. Using a simple mathematical model, we demonstrate that a community-wide treatment program could be instrumental in decreasing HIV incidence rate and eradicating the disease in the future if certain conditions on the parameters are met. On the other hand, when the above mentioned conditions on the parameters are not satisfied, we show that even if the treatment does improve survival in AIDS patients and decrease the rate at which HIV infection spreads in the community, it is still possible for the treatment program to have an adverse effect on the spread of AIDS in the population in the long run. Hence, a public health policy maker must exercise caution in order to design an effective treatment program for HIV/AIDS. PMID- 7772725 TI - A dynamical model of the pulsatile secretion of the hypothalamo-pituitary-thyroid axis. AB - We propose a dynamical model for the hypothalamo-pituitary-thyroid axis. This model takes into account both the interactions of hormones in this axis and the binding of thyroid hormones with proteins in plasma and tissues. It can account for the pulsatile character of hormone secretion in this axis as well as many experimental results. PMID- 7772726 TI - Effects of danazol on thrombopoiesis in rats. AB - A synthetic analog of ethinyltestosterone, Danazol, has been used clinically for the treatment of immune thrombocytopenia. We investigated the effects of Danazol on thrombopoiesis in normal rats. Though 4-week treatment by Danazol slightly enhanced the DNA synthesizing enzyme activities and the number of S-phase cells in bone marrow and spleen, the number of megakaryocytes and thrombocytes were not increased in bone marrow and peripheral blood, respectively. These findings suggest that Danazol treatment will not induce thrombosis with thrombocytosis in normal human beings and animals. PMID- 7772727 TI - Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in adult T-cell leukemia (ATL) in non-ATL-endemic Hokkaido of Japan. AB - Sera and peripheral blood lymphocytes of 40 adult T-cell leukemia (ATL) patients in non-ATL-endemic Hokkaido were examined for the prevalence of human T-cell leukemia virus type 1 (HTLV-I). All patients had HTLV-I-specific antibodies. When the peripheral lymphocytes were assessed after short-term cultivation, HTLV-I antigens and virus particles were detected. The seroprevalence in 96 cases of non T-cell leukemias and lymphomas and in 30,056 healthy individuals in Hokkaido were 3.1% and 0.7%, respectively. HTLV-I seropositive inhabitants of Hokkaido can be estimated at about 40,000, and one out of every few thousand HTLV-I carriers is likely to develop ATL. PMID- 7772728 TI - Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in general inhabitants in non-adult T-cell leukemia (ATL)-endemic Hokkaido, Japan. AB - In contrast to adult T-cell leukemia (ATL)-endemic southwestern Japan, the northernmost island Hokkaido has a small number of ATL patients annually. In this study, we surveyed 32,587 healthy inhabitants throughout Hokkaido for antibodies to human T-cell leukemia virus type 1 (HTLV-I). Only 244 individuals (0.8%) were seropositive as HTLV-I carriers; 0.6% (123 of 19,512) in males and 0.9% (121 of 13,075) in females. In some areas, however, the inhabitants had relatively high seropositivity (> 2%). The highest rate was 5.2% with a cluster of ATL patients in a certain town of the Hidaka area near the Pacific Ocean, in southeast Hokkaido. PMID- 7772729 TI - Modulation of cytokine secretion by mesenteric lymph node cells from vitamin A deficient mice during Hymenolepis nana infection. AB - The influence of vitamin A deficiency on the development of cellular immune responses was examined using vitamin A-deficient mice (A mice)/Hymenolepis nana system. Mesenteric lymph node cells (MLNC) prepared from both normal BALB/c mice and A mice during H. nana infection proliferated extensively when cultured with soluble egg antigen of H. nana as assessed by 3H-thymidine incorporation. MLNC from normal mice secreted significantly more IL-2 and significantly less IFN gamma than A mice when the cells were cultured in the presence of soluble egg antigen. PMID- 7772730 TI - Cryptic dysfunction of cellular immunity in asymptomatic human immunodeficiency virus (HIV) carriers and its actualization by an environmental immunosuppressive factor. AB - Peripheral blood lymphocytes from 4 asymptomatic HIV-1 carriers with normally retained EBV-specific cytotoxic T-cell activity were exposed to EBV and incubated with 0.2 ng/ml 4-deoxyphorbol ester, an immunosuppressive substance derived from an African plant Euphorbia tirucalli. The regression of EBV-induced B-cell transformation by EBV-specific cytotoxic T-cells was significantly impaired in the presence of a small amount of 4-deoxyphorbol ester, but not so in 5 HIV-1 seronegative healthy counterparts. When the EBV-specific cytotoxic T-cells from the asymptomatic carriers were exposed to 0.2ng/ml 4-deoxyphorbol ester and incubated with 51Cr-labeled autologous EBV-transformed B lymphocytes, the released radioactivity was significantly smaller than that of the healthy counterparts. The results suggest that the cellular immunity of the asymptomatic HIV-1 carriers is cryptically impaired, and the cryptic immunological dysfunction is actualized by exposure to a small amount of the immunosuppressive substance, a dose which does not affect the immunity of uninfected healthy individuals. PMID- 7772731 TI - High frequency of telomeric association in a family with multiple congenital neoplasia. AB - Chromosomal analysis of the peripheral blood cultures of a married couple whose second pregnancy gave birth to twin daughters with multiple congenital malignancies revealed normal karyotypes of 46,XX and 46,XY, respectively. However, in the father's blood, 23.3% of metaphases showed telomere-telomere associations involving single-single and double-double chromatids. Such associations were not observed in the metaphases of the mother. We speculate from these observations that the father's genotype may somehow be responsible for the congenital malignancies in their twin daughters. PMID- 7772732 TI - The effects of inhalational anesthetics on ischemic injury of rat kidney with renovascular occlusion. AB - The effects of halogenated inhalational anesthetics, viz. halothane, enflurane, isoflurane and sevoflurane, on ischemic rat kidneys were studied through the response of renal gamma-glutamyl transpeptidase in the brush border of proximal tubules to monoclonal antibodies. Brush border staining characteristics were evaluated as follows: a) continuous (normal), b) discontinuous (damaged) and c) indistinct (necrotic). The isoflurane group had significantly fewer damaged and/or necrotic proximal tubules compared to the other groups. These results suggest that isoflurane is the most appropriate inhalational anesthetic when renal circulation is impaired. PMID- 7772733 TI - Antitumor and cardiotonic activity of imidazo[2,1-b]thiazole guanylhydrazones. AB - A number of imidazo[2,1-b]thiazole guanylhydrazones, whose antitumor activity has already been described, were tested as potential cardiotonic agents. The guanylhydrazone of 2,3-dihydro-6-chloroimidazo[2,1-b]thiazole-5-carboxaldehyde (2a) was the most interesting compound showing both antitumor and cardiotonic activity. PMID- 7772736 TI - Proliferating cell nuclear antigen (PCNA) expression in patients with breast carcinoma in comparison to patients with benign breast diseases. AB - The proliferating cell nuclear antigen (PCNA) was studied by immunohistochemistry on FNA specimens of 20 breast (ductal) carcinomas, 20 fibroadenomas and 20 atypical fibrocystic lesions of the breast. Sixteen cases of breast carcinomas, eight fibroadenomas but no atypical fibrocystic lesions were found to display nuclear PCNA staining. A significant difference was found, between PCNA index of breast carcinomas (mean PCNA index 56%) and fibroadenomas (mean PCNA 21, 25%). This suggests that breast carcinomas display a higher proliferation index than fibroadenomas and fibrocystic disease. Furthermore, we found variations in PCNA among individual cases of breast carcinomas. This suggests that PCNA index can help in the individual approach of the proliferation rate of each tumour, a parameter of potentially importance for predicting the biological behaviour of the tumour in association with other proliferation markers. PMID- 7772734 TI - Aphidicolin inhibits in vitro the activity of pseudorabies virus (PRV) DNA polymerase and in vivo the viral proliferation. AB - We have purified and characterized Pseudorabies virus (PRV) DNA polymerase from infected TK- mouse cells. PRV DNA polymerase has a 3'- > 5' exonuclease activity; it is stimulated by ionic strength, requires magnesium for optimal activity and it is more sensitive to aphidicolin than eukaryotic and HSV-1 replicative DNA polymerases. Aphidicolin inhibits in vitro PRV DNA polymerase competitively with respect to dCTP with a Ki of 0.06 microM and completely blocks viral growth in vivo at 4.4 microM. The high sensitivity to aphidicolin of animal herpesvirus DNA polymerases might allow a topical use of this drug in the treatment of animal herpesvirus keratitis and stomatitis. PMID- 7772735 TI - Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine. AB - Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was examined. Female Donryu rats were divided into four groups at 7 weeks of age. Rats in Croup 1 were controls under a 12-h light/12-h dark regimen while Groups 2 4 were persistent estrous animals maintained under 24-h light conditions. At 10 weeks of age, rats in Group 1 and 2 were given a single intra-uterine administration of polyethylene glycol(PEG), and those in Groups 3 and 4 received ENNG(20 mg/kg body weight), dissolved in PEG, in the same manner. Group 4 rats also received an s.c. 17 beta-estradiol(E2) implant one week thereafter. At the termination of the experiment (week 42 after the ENNG-treatment), all surviving rats were killed and the development of uterine proliferative lesions assessed. All groups demonstrated hyperplasias, the incidence and severity being higher in ENNG-treated animals. The incidence of uterine adenocarcinomas in Group 2(2/20, 10%) was slightly higher than that in Group 1(0/16, 0%), although this difference was not significant. In Groups 3(7/19, 37%) and 4(6/20, 30%) statistically significant induction of adenocarcinomas was noted, two lesions in the latter case being very large with prominent invasion of tumor cells into the perimetrium. At 10 and 25 weeks after ENNG-treatment, the E2-progesterone(E2:P) ratios in Groups 2, 3 and 4 were significantly higher than in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772737 TI - Effects of clinofibrate on plasma fibrinogen level in high fructose diet-induced hyperlipidemic rats. AB - Effects of clinofibrate on the coagulative and fibrinolytic activity in an intrinsic hyperlipidemia induced by a cholesterol free-high fructose diet (HFD) for 14 days were studied using male Wistar rats. There were significant and positive correlations between plasma fibrinogen level and serum lipid content, and between fibrinogen level and VLDL-LDL-lipid content. Clinofibrate administration (50 and 100 mg/kg/day, p.o.) significantly inhibited the increase in plasma fibrinogen level as well as serum- and VLDL-LDL-lipids. It is concluded that clinofibrate, in addition to its beneficial effect on the serum lipid profile, can effectively reduce the plasma fibrinogen level. PMID- 7772738 TI - Malignant squamous cell elements in the ovarian cancer: report of 5 cases and review of the literature. AB - Five cases of ovarian cancer are presented in which malignant squamous cell elements were present. Three of the cases were adenosquamous carcinoma without composite endometriosis, mature cystic teratoma or with mixed mesodermal tumor. The other two cases were squamous cell carcinoma which arose in mature cystic teratoma, one of them being in situ carcinoma. Among cases of adenosquamous carcinoma, one composed predominantly of squamous cell element and foci of endometrioid adenocarcinoma was found. In this case, transitional figures between the two components were found. In other cases of adenosquamous carcinoma, components of adeno- and squamous cell carcinoma were intermingled in each carcinoma cell nests. Thus a large variety of histogenesis and microscopic figures were seen in malignant squamous cell elements in the ovarian cancer. PMID- 7772739 TI - Measurement of ras p21 in the urine of patients with urological tumours. AB - We have measured the product of the ras oncogene, ras p21, in random un-timed urine samples using an immunoblotting method which relies upon enhanced chemiluminescence for visualisation of the nitrocellulose filter. Urine samples were analysed from groups of patients with prostate (n = 10) or bladder (n = 25) cancer and a control group (n = 30) with no apparent urological disease. The mean concentration of urinary ras p21 in the groups with either bladder or prostate cancer was not significantly higher than that of the control group. The most striking difference between the control and clinical groups was the presence of a previously un-reported ras p21 "doublet" in the electrophoretic patterns obtained from 20% of the bladder cancer group and 10% of the prostate cancer group. This doublet was not present in any of the control samples analysed. This doublet is strongly suggestive of a mutation within the ras oncogene. PMID- 7772740 TI - Effects of chronic administration of adenosine antagonists on adenosine A1 and A2a receptors in mouse brain. AB - In the present study the effects of chronic in vivo treatments with caffeine and more selective antagonists (PACPX and PD115,199) on the binding parameters of 3H CHA and 3H-NECA to cortical A1 and striatal A2a adenosine receptors of mouse brain are shown. The drugs were injected intraperitoneally once a day for 6 or 20 days. Treatment for 20 days with caffeine (250 mumol/kg), PD115,199 (50-250 nmol/kg) and PACPX (250 nmol/kg) shifted the A1 low affinity receptors into an agonist-specific high affinity state. Moreover, after 20 days of treatment, the antagonists decreased the affinity of 3H-CHA to A1 receptors in the high affinity state. Antagonist treatments for 6 days did not modify the 3H-CHA binding parameters. The A2a striatal receptors were dose- and time-dependently up regulated by caffeine and PD115,199, whereas PACPX displayed an up-regulation independent of dose or length of treatment. Moreover, PD115,199 decreased the affinity of 3H-NECA to A2a striatal receptors. This effect on affinity was visible after 20 days of treatment with 50 and 250 nmol/kg. This study provides evidence for a sensitivity of A2a receptors greater than that of A1 receptors and for a different regulation of cortical A1 and striatal A2a adenosine receptors of mouse brain after chronic treatment with antagonists. PMID- 7772741 TI - Vitamin C infusion treatment enhances cortisol production of the adrenal via the pituitary ACTH route. AB - The present study is an extension of our past study on the clinical use of vitamin C infusion or injection treatment in autoimmune disease and allergy which suggests that the intravenous introduction of vitamin C may enhance the activity of the endogenous cortisol in such a way as to allow clinical control of immune disorders. This time, we investigated the relation between ACTH, cortisol and vitamin C in plasma in the course of vitamin C infusion or injection treatment with and without the use of methyl-prednisolone annex, a suppressor of the homeostatic mechanism of the pituitary ACTH. A total of 4 experiments were conducted using a healthy male volunteer. Results obtained are as follows: 1) the practice of the steroid-free vitamin C infusion treatment induced a) distinct depletion of both cortisol and vitamin C from the circulation at the initial to moderate stages of the experiment, b) a small surge of plasma cortisol at the middle stage, and c) skyrocket-like rises of ACTH and cortisol of plasma at the terminal stage. 2) The use of methylprednisolone annex in the vitamin C infusion set completely suppressed the emergence of the plasma ACTH/cortisol surges of the terminal stage, but not the small surge of plasma cortisol. The synthetic steroid also suppressed the depletion of vitamin C and cortisol of the initial to moderate stages. 3) The terminal ACTH/cortisol surges of plasma were less distinct in the vitamin C infection experiment than in the vitamin C infusion experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772742 TI - Evaluation of genotoxicity of a technical grade organophosphate insecticide, Tafethion (ethion), in chicks. AB - The genotoxicity of a technical grade organophosphate insecticide, Tafethion (ethion), was evaluated in a chick in vivo test system employing the chromosome aberration assay (CA). Chicks in their neonatal life period are particularly susceptible to environmental contaminants due to the high rate of cell proliferation and ongoing process of development. This provides a new methodology to screen the genotoxic effect of environmental pollutants. The chemical was tested for three different doses (20, 15 and 10 mg/kg b.w.), in two routes of administration (i.p. and p.o.), after three different durations of acute exposure (6, 24 and 48 h) as well as chronic exposure (4 mg/kg day for 5 days), for the induction of chromosomal aberrations. Mitomycin C was used as the positive control. In general, the chemical induced higher frequencies of chromosomal aberrations than the controls, indicating the genotoxic property of the chemical in the tested system. PMID- 7772743 TI - An immuno-electron microscopic study on the relationship between nuclear matrix and DNA in rat spermatocytes. AB - The nucleus of the mammalian spermatid undergoes a series of changes in its chromatin and nucleoprotein composition during transport from testis to epididymis. The sperm DNA is very tightly packaged by protamines instead of histones in somatic cells. However, the nuclear matrix and its association with DNA have not yet been definitively scrutinized with the electron microscope. The present study reveals that the protamine-depleted sperm nuclear matrix appears as a network of thick and thin filaments with glodular structures attached the these fibers. Monoclonal antibody to single- and doublestranded DNA was used to localize remnant DNA after extraction. By immunofluorescence microscopy, monoclonal antibody against DNA was localized outside the nucleus as a halo. Immuno-electron microscopy showed that gold particles were mainly associated with nuclear matrix surrounding the sperm head. Our results suggest a specific structural organization of sperm DNA with its matrix. PMID- 7772744 TI - In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of non-nutrient phenolic compounds on the catalytic activity of liver fractions. AB - Young adult rats were kept on a synthetic diet containing various food associated phenolic compounds each at 0.5% level. The ability of liver microsomes to catalyze reactions of aflatoxin B1 leading to its activation and DNA adduct formation was measured after an experimental feeding period of 3 weeks. A decrease in both activities was observed with several flavonoids (fisetin, kaempferol, morin, naringin and (+/-)catechin), phenolic acids (caffeic acid and chlorogenic acid), other phenolics (eugenol, vanillin) and synthetic phenolic antioxidants butylated hydroxyanisole and butylated hydroxytoluene. Certain phenolics notably naringin, (+/-) catechin, eugenol, vanillin and butylated hydroxyanisole were also found to induce cytosolic glutathione S-transferase activity that stimulated the formation of specific aflatoxin B1-glutathione conjugate. The results emphasize the role of phenolic compounds in the activation and detoxification processes, and hence in modulating the carcinogenicity of aflatoxin B1. PMID- 7772745 TI - Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: I--Diet definition. AB - There is a considerable variation in the diets used in studies on the influence of dietary fat on rat mammary cancer. In view of the fact that diet is the most remarkable factor in these studies, the aim of this work was to define two experimental diets, one of them normal (N3) and another hyperlipidic (HL20), both allowing the normal growth of the rat and neither of them containing factors that could unspecifically affect mammary carcinogenesis. Semisynthetic diets were selected instead of natural ones. A normal diet (3% corn oil, 18% casein, 67.9% dextrose) and a hyperlipidic diet (20% corn oil, 23% casein, 45.9% dextrose) were defined for the rat. Both diets also contain 5% cellulose, 5.9% salt mix and 0.24% vitamin mix. In order to avoid the influence of the above mentioned unspecific factors, the control of specificity and quality of nutrients is proposed as an essential measure. Moreover, it is also necessary to adopt measures to avoid the presence of fatty acid metabolites, including the calculation of the necessary vitamin E, selenium and sulfur amino acid and the determination of factors potentially able to stimulate or inhibit carcinogenesis such as phenolic antioxidants, retinoids or the trans isomer of fatty acids. On the other had, casein, dextrose, choline and folic acid contents were modified in order to equilibrate the lipid increase experimentally introduced in the HL20 diet or to ensure the normal maintenance of the animals' metabolism. The method used is based on the concept of quality assurance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772746 TI - Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: II--Suitability of the diets. AB - We have previously reported one method for obtention of experimental diets for the study of the effects of dietary lipids on the rat breast carcinoma. The purpose of this second part of the study was to develop a quality control system for demonstrating the suitability of these diets. This system is essentially based on the animals' growth control, their period clinical examination as well as the anatomopathological postmortem study of the animals submitted to such diets. Two groups of weaning rats, control (C) and hyperlipidic (HL), were submitted to a low-fat diet (N3) or a high-fat polyunsaturated--corn oil--diet (HL20) respectively. At 53 days of age all animals were induced with 5mg of dimethylbenz (a) anthracene. Experiments were ended when animals reached a mean age of 214 days. The results show: 1) a normal ponderal evolution of the animals in the two experimental groups with respect to two series of the same strain fed with a standard diet, and 2) the homogeneity of growth determined by the coefficient of variance study. On the other hand, neither the weekly clinical examination nor the anatomopathological post-mortem studies revealed any pathology that could be specifically attributed to nutritional imbalance. These results confirm the suitability of both diets for rat growth. Their use in the study of the effects of dietary lipids on the mammary carcinoma would satisfy the initial aim of guaranteeing the specificity of the results. PMID- 7772747 TI - Clonal outgrowths of T and B cells in SCID mice reconstituted with cells from mice with MAIDS. AB - Murine acquired immunodeficiency syndrome (MAIDS), induce in mice by a defective murine retrovirus (BM5def), is characterized by development of severe immunodeficiency and polyclonal lymphoid proliferation which progress to yield oligoclonal populations of T and B cells. Oligoclonal populations transferred to SCID mice grew as clonal CD4+ T cell or B cell lineage transplants having one or more unique clonal integrations of BM5def. In some cases, spleens of single donor mice were shown to contain both B cell and T cell lineage clones that could be transferred individually after separation and were clonally unrelated. Successful transplants were obtained from oligoclonal populations as early as 63 days after infection. Mouse strains both sensitive or moderately resistant to MAIDS yielded clonal transplants. PMID- 7772748 TI - Embryonal carcinoma cells differentiate into parietal endoderm via an intermediate stage corresponding to primitive endoderm. AB - F9 embryonal carcinoma (EC) cells were used as a model system to study endoderm formation during mammalian embryogenesis. F9 cells treated with retinoic acid (RA) or RA plus dibutyryl cyclic AMP (cAMP) were examined for the expression of stage-specific embryonic antigen-3 (SSEA-3), a cell surface marker of primitive and visceral endoderm. SSEA-3 was not detected by indirect immunofluorescence on the surface of undifferentiated stem cells; however, a subset of SSEA-3-positive cells appeared with time in culture, amounting to 20% of cells 10 days after plating. When cultured in the presence of RA, the percentage of SSEA-3-positive cells increased to 70% of cells 10 days after plating. In contrast, treatment of cells with RA plus cAMP yielded differentiated cells that were SSEA-3-negative. These SSEA-3-negative cells exhibited ultrastructural features of parietal yolk sac endoderm. In contrast, SSEA-3-positive cells appearing in cultures treated with RA alone exhibited ultrastructural features of primitive endoderm on day 3, switching to ultrastructural features of parietal endoderm on day 10. Cells with hybrid features, resembling both visceral and parietal yolk sac, were also seen. We suggest that differentiation of F9 EC cells into parietal yolk sac-like cells can occur along two distinct pathways: 1) direct under the combined influence of RA and cAMP; and 2) indirect, under the influence of RA alone, in which cells first differentiate into primitive endoderm. Parietal yolk sac-like cells induced through the latter pathway continue to express SSEA-3, a cell surface marker of primitive endoderm that is not normally found on parietal endodermal cells in vivo. PMID- 7772749 TI - Preclinical toxicology study of liposome encapsulated doxorubicin (TLC D-99) given intraperitoneally to dogs. AB - A preclinical toxicology study of intraperitoneally administered liposome encapsulated doxorubicin and free doxorubicin was carried out in beagle dogs. Dogs received single intraperitoneal infusions of 1.5 mg free or 1.5, 2.25 or 3.37 mg liposomal doxorubicin/kg. One group of four dogs received 1.5 mg liposomal doxorubicin/kg every three weeks for 4 cycles. The dose limiting toxicity of free or liposomal doxorubicin given by the intraperitoneal route was a dose-related chemical peritonitis. This toxicity was more severe in dogs that received by the intraperitoneal route the previously determined maximally tolerated intravenous dose of liposomal doxorubicin (2.25 mg/kg). The abdominal toxicity was characterized by capsular fibrosis and ascites formation. Abdominal toxicity was life threatening after single doses of 3.37 mg liposomal doxorubicin kg, or after multiple (4) doses of 1.5 mg liposomal doxorubicin/kg. Thoracic toxicity (increased fluid, mediastinal edema, thickening of the parietal pleura) was seen after multiple (every 3 weeks for 4 cycles) intraperitoneal doses of 1.5 mg or single doses of 3.37 mg liposomal doxorubicin/kg. Myelosuppression was seen in all groups, but was less severe after intraperitoneal dosage than after intravenous dosage of liposomal doxorubicin. PMID- 7772750 TI - Immunomagnetic isolation of endothelial cells from normal rat prostate tissue. AB - Angiogenesis, or the process of the formation of new blood vessels, is an essential event for the successful growth of tumors in vivo. The discovery of agents which inhibit angiogenesis has been limited by the lack of available experimental endothelial cell systems which mimic specific organ- or tumor derived endothelial cells. It is well recognized that there are measurable functional and morphological differences between normal tissue endothelium and tumor vessels, however, the cause of these differences remains unclear. We report here a technique for tissue specific endothelial cell isolation from the rat prostate utilizing immunomagnetic techniques, providing a tool for the study of endothelial cells and their inhibition. PMID- 7772751 TI - Immunoprotective activity of the galactoside-specific mistletoe lectin in cortisone-treated BALB/c-mice. AB - Hydrocortisone-acetate (HA)-treatment of BALB/c-mice induced a profound suppression of the lymphatic immune system with statistically significant decreases of thymocyte proliferation and maturation rates as well as peripheral blood lymphocyte (PBL) counts. To check its putative immunoprotective/immunorestoring activity, the optimal immunomodulating dosage of commercially available mistletoe extract standardized for the galactoside specific mistletoe lectin (ML-1) was regularly administered (1 ng ML-1 per kg body weight; subcutaneously). As compared to counts of thymic lymphatic subsets of HA-treated mice, a considerable up regulation of mature cells expressing helper/inducer (L3T4+) as well as cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells expressing both antigens (L3T4+/Lyt-2+) could be found after ML-1 co-administration. Counts of BALB/c-mouse peripheral blood mononuclear cells also revealed statistically significant increases after ML-1 co-administration, as compared to HA-treated animals. Accordingly, ML-1 treatment may be supposed to restore the lymphatic system after immunosuppressive corticoid treatment and thus this treatment may be of great benefit to patients. PMID- 7772753 TI - Gyromitra esculenta mushroom: a comparative assessment of its carcinogenic potency. AB - A comparative assessment is performed on one of the false morel mushrooms, Gyromitra esculenta, including the amounts of some hydrazines present in this fungus, the cancer-inducing doses of these chemicals or the mushroom used in animal experiments, the total amounts of the hydrazines or mushroom needed to induce neoplasms in mice and the estimated total amounts of hydrazines or mushroom needed to induce cancer in humans. When one compares the estimated amounts of hydrazines required to induce cancer with the amount of raw Gyromitra esculenta needed to yield a similar effect, it becomes clear that to date 37 percent of the carcinogenic ingredients of this fungus have been identified. PMID- 7772754 TI - [The first specialist of radiology....]. PMID- 7772752 TI - Hypocholesterolemic effect of exogenous dehydroepiandrosterone administration in the rhesus monkey. AB - The effect(s) of exogenous dehydroepiandrosterone (DHEA) was studied in healthy non-obese rhesus monkeys. Six monkeys were given 60 mg/kg/day DHEA for 4 weeks. The dose was then increased to 75 mg/kg/day for an additional 4 weeks. Another six monkeys were given placebo, daily for 8 weeks. Body weight, activity level, average daily food intake, and plasma T4, insulin, total androgen and cortisol concentrations remained unchanged for all 12 monkeys throughout the 8 weeks. Both groups had a significant (p < 0.05) decrease in total plasma cholesterol, however the DHEA treated monkeys were significantly lower than the placebo monkeys. The change in cholesterol in the DHEA treated group primarily affected the fraction containing the low density lipoprotein cholesterol which remained overall unchanged for the placebo monkeys. Both groups had a decrease in high density lipoprotein cholesterol, however there was no difference between the treatment groups. We conclude that in the rhesus monkey, exogenous administration of DHEA acutely reduces cholesterol concentration, particularly the lipoprotein fraction containing low density lipoprotein, without changing food intake, activity level, or body weight. PMID- 7772755 TI - [The filmless hospital: reality or illusion]. PMID- 7772756 TI - [The riddle of the first clinical x-ray solved]. PMID- 7772757 TI - [Value of thoracic radiography in the assessment of cardiac size. A comparison with left ventricular cardiography]. AB - PURPOSE: To determine the value of standard chest radiographs in the assessment of cardiac size. METHODS: In 193 patients cardiac size was compared between standard chest radiographs in the posteroanterior and lateral projection and left ventricular angiograms. The following parameters were determined: transverse diameter, lateral horizontal transverse diameter, cardiothoracic ratio and end diastolic volume index (EDVI) and ejection fraction (EF). RESULTS: Subjective assessment of the left ventricular size resulted in a mean sensitivity/specificity/accuracy of 69.7%/87.4%/82.0% respectively, in comparison to EDVI. Estimation of global heart size yielded a mean sensitivity/specificity/accuracy of 48.8%/93.6%/77.8%, respectively, in comparison to EF. Cardiothoracic ratio for the detection of pathological EDVI or EF had a sensitivity of 77.3%/57.4% a specificity of 79.3%/80.8% and an accuracy of 78.9%/72.5%. CONCLUSIONS: Standard chest radiographs with the determination of cardiothoracic ratio remain a clinically relevant procedure for screening and follow-up of heart disease. PMID- 7772758 TI - [CT angiography in carotid stenosis. Diagnostic value compared to color-coded duplex ultrasonography and MR angiography]. AB - PURPOSE: To evaluate the accuracy of different diagnostic methods for the visualization of the carotid arteries and their pathological changes in order to avoid invasive angiography whenever surgery was considered. MATERIAL AND METHODS: 24 patients with clinically suspected stenosis or occlusion of the carotid arteries were prospectively examined via CT angiography. MR angiography and colour-coded duplex sonography (ccds) to evaluate the degree of stenosis and the extent of calcification. RESULTS: In 36 cases stenoses of different extent could be documented with CT angiography, 33 cases were found using colour-coded duplex sonography and MRA. Sonography could not prove mild stenoses (< 30%), and in two patients with sonographically suspected total occlusion vessel perfusion was documented via CT angiography. MR angiography led to a overestimation in patients with high-grade stenosis compared to the degree of stenosis obtained via ccds and CTA. With regard to the diagnosis of calcification MIP, reconstructions after CT examination showed best correlation to the plain CT slices referring to length (94.6%) and thickness (89.2%). CONCLUSION: CTA with MIP reconstructions is an excellent screening method and, in combination with ccds, CT angiography may replace DSA before surgery or intervention. PMID- 7772759 TI - [MR mammography at 0.5 tesla. I. Comparison of image quality and sensitivity of MR mammography at 0.5 and 1.5 T]. AB - PURPOSE: To determine whether dynamic MR mammography is possible on midfield systems without loss of diagnostic sensitivity when compared to the standard highfield technique. MATERIALS AND METHODS: 42 consecutive patients were examined twice: Once using the standard dynamic 2D gradient echo technique at 1.5 T; a second examination was performed on a 0.5 T system. For the midfield examinations a 3D sequence with optimized T1 contrast was used to compensate for the shorter T1 relaxation times at 0.5 T. Subtraction images were calculated to improve detectability of enhancing lesions. RESULTS: Image quality was comparable on both systems. Mean enhancement of lesions was higher at 0.5 T/3D as compared to 1.5 T/2D (161% versus 112%). In malignant lesions, enhancement at 0.5 T/3D surpassed that at 1.5 T/2D in 88% of cases; average maximum signal intensity increase of cancers was significantly higher at 0.5 T/3D as compared to 1.5 T/2D (183% versus 108% relative to baseline). One satellite lesion of a recurrent carcinoma was detected on the 0.5 T/3D images only. CONCLUSION: A 3D gradient echo pulse sequence can be used to compensate for the T1 shortening effect of the lower field strength. With a 3D sequence, sensitivity of MRM at 0.5 T is even superior to that of the standard 2D highfield technique. PMID- 7772760 TI - [MRI of the knee joint: first results of a comparison of 0,2-T specialized system and 1,5-T high field strength magnet]. AB - PURPOSE: Diagnostic accuracy and image quality of a specialised system for MR examinations of peripheral joints were evaluated. MATERIALS AND METHODS: 20 patients with acute or chronic injuries of the knee were examined using a low field MR system (0.2 T). For comparison, all patients were also studied with a 1.5 T high field strength magnet and all diagnoses were correlated with arthroscopic findings. RESULTS: We found compatible diagnostic accuracies (cruciate ligaments 90%, menisci 75-90%) and good image quality ratings for the low field system ("good" and "excellent" image quality in 83% of cases). CONCLUSION: The low-field MR-system offers low-cost MR examinations of peripheral joints with good image quality and reliable diagnostic information. PMID- 7772761 TI - [Static and dynamic MR tomography of the pancreas: contrast media kinetics of the normal pancreatic parenchyma in pancreatic carcinoma and chronic pancreatitis]. AB - PURPOSE: We aimed both at improving image quality and diagnostic value of pancreatic MRI by using fast multislice imaging techniques and at demonstrating normal and pathologic signal enhancement in the pancreas after i.v. gadopentate dimeglumine. METHODS: MR imaging at was performed in 30 patients with suspicion of pancreatic neoplasm or chronic disease and in 15 patients without pancreatic abnormalities. RESULTS: SNR, CNR, mean signal enhancement, and time/signal intensity curves were calculated. Signal enhancement after i.v. Gd-DTPA averaged 34.4% in neoplasms (n = 14) vs 58.8% in pancreatic tissue not involved by tumour (p < 0.05) in T1-w SE and was also significant in the T1-w GE sequence (p < 0.005). CNR (pancreas vs lesion) and SNR improved significantly (p < 0.005; pancreas: p < 0.001; lesion: p < 0.05) after i.v. Gd-DTPA administration. In patients without pancreatic disease enhancement curves of pancreas demonstrate a rapid signal increase (79.0% after 34 s). Patients with adenocarcinoma or chronic pancreatitis demonstrated flattened signal intensity curves and higher peak signal intensity values (90.1, 111.3% after 68 s). The slope of signal increase of neoplastic tissue was significantly different (p < 0.01) from unaffected parenchyma (48.3% after 51 s, 90.1% after 68 s). CONCLUSION: MR imaging with fast T2-w SE and T1-w SE sequences provides excellent visualisation of the pancreas and adequate conspicuity of pancreatic adenocarcinoma. Following i.v. Gd-DTPA significant enhancement of tumour/parenchyma contrast is found. PMID- 7772763 TI - [Color-coded duplex ultrasonography in the diagnosis of renal artery stenosis]. AB - PURPOSE: Colour-coded duplex sonography was performed for diagnosis of renal artery stenosis to define standards and criteria for stenosis. MATERIAL AND METHODS: In 20 normotensive volunteers and 123 patients with arterial hypertension, bilateral intrarenal Doppler spectra were examined and the following parameters including side ratios were calculated: pulsatility index (PI), resistance index (RI), acceleration time index (AT) and acceleration index (AI). RESULTS: In 29 of the 123 patients, angiography showed unilateral renal artery stenosis. Acceleration index (AI) was found as the most reliable parameter with a sensitivity of 100% and a specificity of about 94% for stenoses grading at least 70%. CONCLUSIONS: Colour-coded duplex sonography can depict relevant stenoses reliably, but anatomical variations may limit its value as a single screening method. Colour-coded duplex sonography can be, therefore, recommended as an adjunct to angiography for assessment of haemodynamic relevance. PMID- 7772762 TI - [Multiple slab MR angiography of the A. carotis interna: a preoperative comparative study]. AB - PURPOSE: With the introduction of MR angiography (MRA) into clinical routine, arteriosclerotic lesions of the supraaortic vessels may be well demonstrated. MATERIAL AND METHODS: The comparison between Multislab MRA (gradient echo, TOF) and X-ray angiography (XRA) as reference in 70 patients suspicious of stenotic lesions in the internal carotid artery proved the high reliability of these methods. RESULTS: In determining the degree of stenosis, according to the NASCET study (North American Symptomatic Endarterectomy Trial), a correlation between MRA and XRA of 92.3% could be calculated. The principal problem of MRA is the overestimation of high-grade stenoses; we observed 5 false-positive results in severe stenosis. Sensitivity and specificity were 95.6 and 92.6%, respectively, for detection of severe (> 60%) stenosis. CONCLUSION: Despite its limitations, MRA is a clinically important noninvasive technique for preoperative evaluation of patients undergoing carotid endarterectomy. PMID- 7772765 TI - [First clinical experience with a new nitinol stent in the biliary system]. AB - PURPOSE: To evaluate the clinical usefulness of a new nitinol biliary stent (Memotherm) in patients with malignant biliary obstruction. 32 self expanding nitinol stents were applied in 17 patients. The following parameters were investigated: Difficulty of placement, lateral stability and patency over an observation time between 3 weeks and 11 months. RESULTS: In 29/32 stent application could be performed with high precision. In 3/32 we observed a displacement about 1 cm--according to the optimal stent position. Stent shortening was about 5 mm in 31/32 stents, secondary shortening only occurred in one patient with primarily distracted stent design. Lateral stability was sufficient in 21/25 stenoses with the consequence that dilatation was only performed in 4 cases. Average stent patency was 4.8 months, the average survival 5.1 months. Because of his special design, this stent may not be used for a stenosis with angulation higher than 90 degrees. CONCLUSION: Basing on a small calibre introducing system, easy placement, predictable minimal shortening and good lateral stability, the Memotherm seems an interesting alternative to other metal stents. PMID- 7772764 TI - [Duplex ultrasonographic diagnosis of renal artery stenosis by intrarenal acceleration determination and recognition of the tardus-parvus phenomenon with special regard to multiple renal arteries]. AB - PURPOSE: Use of the "tardus and parvus" abnormalities for the exclusion of significant renal artery stenosis, including multiple renal arteries. METHOD: The lobar and interlobar renal arteries of 50 hypertensive patients were examined by colour duplex sonography at three different levels. Analysis included determination of the early systolic acceleration time and evaluation of the early diastolic complexes. In all patients, intra-arterial catheter angiography was performed on the following day. RESULTS: 48 out of the 50 colour duplex examinations could be properly evaluated. Angiography showed that 21 patients (42%) had multiple renal arteries, in 13 there was a haemodynamically significant renal artery stenosis and amongst these 4 patients had bilateral renal artery stenoses. The sensitivity and specificity of the early systolic acceleration time at > or = 0.120 sec. was 77 and 46% respectively. Amongst the 17 haemodynamically significant stenoses shown by angiography, 10 demonstrated changes in the early systolic peaks of the Doppler spectrum, a sensitivity of 69% and specificity of 90%. CONCLUSION: Use of acceleration time and of the early systolic complexes cannot be recommended as sole methods during a screening procedure. PMID- 7772766 TI - [Adaptable hourglass stent to reduce shunt flow after TIPS insertion]. PMID- 7772767 TI - [CSF fistula through the clivus Blumenbachii]. PMID- 7772768 TI - [Juvenile nasopharyngeal angiofibroma and antro-choanal polyp: role of MRT in the differential diagnosis]. PMID- 7772769 TI - [Pseudotumorous heterotopic ossification of the hand]. PMID- 7772770 TI - [Long-term follow up of therapy-conditioned cerebral changes in acute lymphatic leukemia]. PMID- 7772771 TI - [Catheter lysis in embolism of the superior mesenteric artery]. PMID- 7772772 TI - 5th International Conference on Adjuvant Therapy of Primary Breast Cancer. St. Gallen, Switzerland, 1-4 March 1995. Abstracts. PMID- 7772773 TI - [Remission and recurrence of chronic obstructive lung disease in air pollution caused lung disease patients in the Yokkaichi area]. AB - A study was conducted of patients covered by National Health Insurance (NHI) with chronic obstructive lung diseases legally-recognized as being caused by air pollution (Group A) and those not legally-recognized as air pollution caused (Group B) in the Yokkaichi area. Records of medical examinations (medical fee NHI statement), were examined, focusing on recurrence and remission. Over all incidence of recurrence after remission in asthmatic bronchitis and bronchial asthma conditions was 25% in Group A and 18% in Group B patients although with differences observed in different age groups. Approximately 50%-70% of the recurrence occurred within 3 years, and this incidence decreased approximately in proportion to time elapsed. Total remission rates for patients who had remission without recurrence and those who had remission after recurrence of bronchial asthma was approximately 39% in Group A and about 77% in Group B. PMID- 7772774 TI - [Childcare problems and maternal fatigue symptoms in families with twins and triplets]. AB - A mailed questionnaire survey was conducted on a population of 123 mothers of twins and 96 mothers of triplets to study problems in the families and maternal fatigue symptoms. The following results were obtained. 1) The prevalence rate of handicap was 9.7 per 100 for triplets, and 4.9 per 100 for twins. The risk of handicap in triplet pregnancy was approximately 25%, and in twin pregnancy was approximately 10%. Therefore 1 in 4 mothers with triplets and 1 in 10 mothers with twins had one and more handicapped children. 2) Mothers with triplets aged 0 11 months reported significantly poorer sleep quality than mothers with triplets aged one year or more with shorter sleeping time, greater frequency of awakening during the night, and more complaints of inadequate sleep. Mothers with twins aged 0-11 months showed a greater tendency for poor sleep quality than mothers with twins aged one year or more. 3) Approximately 70% of mothers with twins and triplets aged up to two reported lack of time to care for the other children. When the age of twin was 3 or more, lack of time to take care of other children was reported by only 13.3% of mothers, while it was 41.7% for mothers with triplets. 4) Mothers of twins and triplets who did not receive assistance from others for childcare reported severe physical fatigue, compared to mothers who received assistance from others. Mothers of twins and triplets aged 3 or more showed a tendency of less physical fatigue, compared to mothers of twins and triplets aged up to two. PMID- 7772775 TI - [Yearly changes and geographical distribution of allergic rhinitis morbidity estimated from records of the national health insurance]. AB - The age-adjusted morbidity of allergic rhinitis (AR) in Ibaraki prefecture in May, estimated from data of national health insurance records, increased remarkably from 1980 to 1992 with varying yearly rates of increase. High AR morbidity years coincided with years of high Japanese cedar and cypress pollen counts, and moreover, an estimate equation of the morbidity using as explanatory variables, year and the yearly total count of pollen, accurately estimated AR morbidity. The AR morbidity varied with the size of the municipality. The AR morbidity of the town group and village group were about 80% and about 60% respectively of the city group in 1992. The map of the AR morbidity of each municipality showed that urbanized districts had higher morbidity than areas with cedar forests, which are supposedly sources of the cedar pollen. Continuous increase of morbidity of districts with much cedar forests terminated in 1986. Since then only the fluctuation of the morbidity corresponding to the pollen count was observed. The ratio of the morbidity of the years with much pollen to that of the years with little pollen was mapped. The map showed good agreement with the map of cedar forests. The results obtained above demonstrate the usefulness of the data of the national health insurance records. PMID- 7772776 TI - [Psychosocial determinants of changes in activities of daily living and depressive status among stroke patients at home]. AB - Using a longitudinal study of 79 stroke patients, factors that are predictive of change in activities of daily living (ADL) and depressive status over three and a half-year period were examined. Social activities, health behavior, and depressive status were entered as predictive variables. Those who participated in community activities, had significantly less decline in ADL than those who did not, and those who reported a greater variety of leisure activities had less decline in depressive status during the follow-up period. PMID- 7772777 TI - [Health screening behavior in the past 5 years and the next year of attendance of 40 and 50 years of age at individual screening and the related factors]. PMID- 7772778 TI - [A follow-up study for length of stay and readmission rate of psychiatric inpatients in a rural area]. PMID- 7772779 TI - [Childbirth by traditional birth attendants in a remote island of Okinawa]. PMID- 7772780 TI - Development of hearing. Part III. Postnatal development. AB - As humans, we 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. The second is embryology, the formation of the system in each individual. Finally, there is the interaction between the biologically determined mechanism we are born with and the environment. This series of articles reviews each aspect in turn, so that we may have a fuller appreciation of how it is we come to hear the way we do. Part I examined how the auditory system evolved, and Part II outlined the sequence of ear formation in prenatal life. In this concluding article, we examine the development of auditory perception from when we first hear (in utero) through 12 months of age, which is when speech usually appears. Humans seem to come "programmed" to perform all the processes necessary to learn the language of their environment. Interaction with the environment hones our abilities to process sound and thereby optimizes language acquisition and production. PMID- 7772781 TI - Differences in localization ability in cases of right versus left unilateral simulated conductive hearing loss. AB - The purpose of this study was to determine whether localization errors were greater in cases of right ear unilateral simulated conductive loss, as compared to left ear simulated conductive loss of the same degree and configuration. Thirty adults were asked to localize a 3-kHz warbled pure tone with their left and right ears alternately occluded with an earplug. Significantly greater localization difficulty was found when the right ear was occluded. The average error was 58 degrees with the left ear plugged and 64 degrees when the right ear was occluded, which approximates the 65-degree average error that would have resulted from random guessing. This suggests that short-term conductive losses result in unusually poor localization ability, which is worse if the right ear is affected. PMID- 7772782 TI - Disabilities and handicaps associated with impaired auditory localization. AB - A questionnaire on (1) difficulties in everyday sound localization (localization disabilities), (2) limitations and disadvantages related to such disabilities (localization handicaps), and (3) everyday speech hearing disabilities was completed by 104 people with symmetrical hearing losses. Respondents considered situations when listening with and without their usual hearing aid fittings. The hearing-impaired group rated their unaided localization ability as significantly poorer than a sample with no reported hearing loss, particularly discrimination of distance. Only slight limitations on everyday activity due to localization disability were found, but disadvantage was reported in the form of experiences of confusion of sounds, of resultant loss of concentration, and of a wish to escape settings where this occurred. There was a moderate correlation between localization and speech hearing, even when hearing level was controlled for. Aided listening, whether with one or with two hearing aids, was reported as enabling significant improvements in both functions. PMID- 7772783 TI - Long-term recovery and no recovery from the auditory deprivation effect with binaural amplification: six cases. AB - Six subjects who developed individually significant auditory deprivation effects associated with monaural amplification were tracked for 6.2 to 15.1 years from the time of their initial hearing aid fitting. Each subject received binaural hearing aids after the auditory deprivation effect became apparent and used binaural amplification for at least 4 years. The findings corroborate and expand upon existing case reports. Several general configurations of recovery and no recovery following the introduction of binaural amplification were identified: (1) cases in which auditory deprivation effects developed within about 2 years and recovered completely within about 2 years of binaural use; (2) cases with significant but incomplete recovery; and (3) cases in which the auditory deprivation effect took several years to develop and did not recover following several years of binaural amplification. Clinical implications of the results are proposed. PMID- 7772784 TI - Preliminary descriptions of transient-evoked and distortion-product otoacoustic emissions from graduates of an intensive care nursery. AB - Transient-evoked (TEOAE) and distortion-product otoacoustic emissions (DPOAE) were measured in 51 graduates of an intensive care nursery and compared to data obtained from 80 normal-hearing children and adults. All infants had click-evoked auditory brainstem responses (ABR) at 30 dB nHL or less while the older subjects had pure-tone thresholds of 20 dB HL or less for octave frequencies from 250 to 8000 Hz. OAE data were collected using commercially available devices. All data were analyzed in terms of emission amplitude, emission-to-noise ratio, and response reproducibility as a function of frequency. DPOAEs were measured at three points per octave between f2 frequencies of approximately 500 and 8000 Hz. TEOAEs were elicited by clicks and were analyzed in both octave and 1/3-octave bands centered at frequencies from 500 to 4000 Hz, as well as in the broadband condition. In addition, stimulus amplitudes for the clicks used to elicit TEOAEs were analyzed within octave and 1/3-octave bands to determine whether any age related differences in responses can be accounted for on the basis of stimulus differences. Both emission amplitude and noise amplitude were greater in neonates than adults, although there was variability across frequency. Emission-to-noise ratio and response reproducibility were more similar between groups. For TEOAEs, high-frequency emission-to-noise ratios were larger in neonates compared to older subjects, while the reverse was true in the lower frequencies. Less obvious frequency effects were observed for DPOAEs. These findings are discussed in relation to the potential use of OAEs as screening measures for neonatal hearing loss. PMID- 7772785 TI - Case of recurrent, reversible, sudden sensorineural hearing loss in a child. AB - This paper describes audiologic, electrophysiologic, and medical test results for a now 10-year-old girl who has had 45 episodes of reversible, sudden sensorineural hearing loss over the last 8 years. Episodes have lasted from 6 to 72 hours and often have been accompanied by a mild illness. Acoustic immittance measures have been consistent with normal middle-ear function with the exception of absent ipsilateral and contralateral acoustic reflexes. Mechanically evoked perioral reflex activity was markedly asymmetric following lower lip stimulation. The asymmetry of R1 activation between right and left side lower lip inputs raises questions about the integrity of central connections within the brain stem, including internuncial pathways coursing between trigeminal sensory relay nuclei and the facial motor nucleus. An electrocochleographic evaluation revealed cochlear microphonic but absent or markedly abnormal whole nerve action potentials. Auditory brainstem responses (ABR) have been either absent or poorly formed and significantly delayed, regardless of hearing sensitivity. Middle and late auditory evoked potentials were essentially normal. Both transient-evoked and distortion-product otoacoustic emissions were present regardless of peripheral auditory sensitivity. All medical tests have been essentially normal. Although no definitive diagnosis has been reached, beta blockers have been used with some success. Taken together, these data document a very unusual case of fluctuating hearing loss. The electrocochleographic and otoacoustic emission data suggest that the outer hair cells are functioning normally and that the loss is not cochlear in origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772786 TI - Evaluating relative speech recognition performance using the proficiency factor and rationalized arcsine differences. AB - This study evaluated two measures that have been used to compare the performance of particular subjects to outcomes predicted by the articulation index (Al). One measure was the proficiency factor, that is, the ratio between the Al derived from a test score and the Al derived from objective measurements of speech and noise spectra. The other measure was the difference between rationalized arcsine transforms of the observed score and the score predicted from the Al. The results indicated that rationalized arcsine differences are statistically superior to proficiency factors for comparing two sets of scores. Proficiency factors are best used to correct the Al, and thus an expected score, for the effects of subject variables that might bias the comparison. An assessment procedure that combines the strengths of both measures is described. PMID- 7772787 TI - Relative intelligibility of the revised CID W-1s as presented via MLV and auditec recordings. AB - The relative intelligibility of the revised CID W-1 spondaic word list, as developed and recommended for clinical use by ASHA, was evaluated in two experiments. In Experiment 1, the revised W-1s were presented via monitored live voice to 25 subjects with normal hearing. Mean minimum recognition levels for each of the 36 spondees varied between 16.8 and 25.2 dB SPL, a range of 8.4 dB. In Experiment 2, the Auditec recordings of the revised W-1s were presented to a different group of 20 subjects with normal hearing. Mean minimum recognition values for the individual spondees varied between 18.1 and 30.6 dB SPL, a range of 12.5 dB. Thus, the homogeneity of audibility for the revised W-1s is no better than has been noted in the past for the original W-1s and, in the case of the Auditec recording, is considerably worse. A reduced list of spondees with improved homogeneity of audibility is recommended for clinical use. PMID- 7772788 TI - Use of maximum length sequence analysis in newborn hearing testing. AB - The use of maximum length sequence analysis (MLSA) with rapid click rates may be of clinical value in newborn hearing screening because a greater number of individual responses can be signal averaged without adding to test time. To examine the potential clinical value of MLSA in newborn screening, auditory brainstem responses (ABRs) from 50 premature newborns were studied. ABRs were acquired with conventional signal averaging at four stimulus intensity levels (50 dB, 40 dB, 30 dB, and 20 dB nHL) using a click rate of 33.3/sec. These responses were directly compared with the ABRs acquired with MLSA using a rate of 227.3/sec. MLSA and conventional signal averaging yielded similar results with no statistically significant differences in the number of responses detected. Across babies, the overall quality of the tracings slightly favored MLSA, particularly when recording conditions were poor. Though the results of this investigation do not support the use of MLSA as the primary technique in newborn screening in the neonatal intensive care unit (NICU), they do support consideration of the use of MLSA as an alternative technique when the responses obtained with conventional signal averaging are poorly defined. PMID- 7772789 TI - Infant hearing screening. PMID- 7772790 TI - An ultrashort clock mutation at the period locus of Drosophila melanogaster that reveals some new features of the fly's circadian system. AB - A rhythm mutant of Drosophila melanogaster was induced by chemical mutagenesis and isolated by testing for locomotor activity rhythms, which in the new variant had periods of approximately 16 hr. The sex-linked mutation responsible for this ultrashort period causes 20-hr rhythms when heterozygous with a normal X. This semidominance notwithstanding, the new mutation was revealed to be an allele of the period (per) gene by noncomplementation with per-null variants, in the sense that females heterozygous for perT (as the ultrafast-clock allele is called) and per- exhibited periods that were much shorter than in the case of perT/+. These tests also revealed in a clearer manner than in previous cases that two "doses" of a fast-clock per mutation lead to appreciably shorter periods than those exhibited by one-dose females whose other per allele is a loss-of-function variant. In light-dark cycles (LD 12:12), flies carrying perT in a genotypic condition leading to free-running periods that are 8 hr faster than normal nevertheless entrained, by phase-shifting that large number of hours each day; the evening peak of locomotor activity was, however, many hours earlier than normal. The use of a newly developed device for monitoring Drosophila eclosion automatically showed that perT exhibits a very marginal emergence rhythm at 25 degrees C, but periodicity of ca. 17-18 hr at 19 degrees. Staining of the per encoded protein (PER) in sections of perT versus normal pharate adults revealed for the first time that the immunohistochemically detected signal cycles in its intensity in wild-type, in a manner that is similar to the PER rhythm previously demonstrated in adults. The staining cycle in pharate adults expressing perT differed from that of wild-type. Temperature compensation of the adult activity rhythm of perT was found to be faulty, in that periods became appreciably shorter as the flies were heated. However, the mutant exhibited a normal degree of period lengthening when its locomotor activity was monitored in the presence of heavy water. The perT mutation interacted with the long-period Andante allele of the dusky locus in a manner that was anomalous (in comparison to dyAnd interactions with per+ or another short-period per mutation). This and other unique features of perT are discussed from the standpoint of the new mutation's heuristic value, including that which may stimulate a deeper understanding of the period gene's action at the molecular level. PMID- 7772791 TI - Differential photoperiodic control of seasonal variations in pulsatile luteinizing hormone release in long-day (ferret) and short-day (mink) mammals. AB - The aim of this study was to elucidate the pituitary adjustments implicated in photoperiodic control of reproduction in two mammalian species, the ferret and the mink. In the ferret, which displays renewed testicular activity when the days lengthen, we observed a stimulation of the pulsatile liberation of luteinizing hormone (LH) reflecting the pulsatile activity of the gonadotropin-releasing hormone (GnRH) system when daylight was equal to or in excess of LD 8:16. This photoperiod coincides precisely with the phase of photosensitivity known to be essential for gonadal stimulation in this species. In the mink, which displays renewed testicular activity when the days shorten, pituitary stimulation was activated when daylight was reduced to LD 11:13, and gonadal stimulation occurred only when daylight was further reduced to LD 10:14. In addition to requiring different photoperiodic stimuli to trigger the seasonal reproductive process, the two species display variations in the "timing" of pituitary control of renewed gonadal activity. PMID- 7772793 TI - Inhibition of GABA transaminase enhances light-induced circadian phase delays but not advances. AB - The CNS neurotransmitter GABA is distributed extensively throughout the suprachiasmatic nucleus, the site of circadian pacemaker cells in mammals. Pharmacological agents that act at GABAA receptors alter specific circadian responses to light and may induce phase shifts of circadian rhythms. In the present study, the role of endogenously released GABA in rhythm regulation was investigated using vigabatrin (gamma-vinyl GABA), an agent that has been shown to increase chronically or acutely the CNS levels of this neurotransmitter by inhibiting GABA transaminase. In Experiment 1, hamsters in constant darkness (DD) received a saline or a vigabatrin injection 1 hr before a 15-min, 700-lux light pulse. Vigabatrin increased photic phase delays but did not affect advances. In Experiment 2, vigabatrin delivered chronically via osmotic minipump treatment did not affect locomotor activity period in DD. However, after 14 days of infusion, photic phase delays (but not advances) were greatly increased in the vigabatrin group. In Experiment 3, in constant light (LL), chronic vigabatrin-treated animals showed an increased period that returned to pretreatment values after the 14-day drug infusion. The results are consistent with the phase-dependent effects of other agents that alter GABA neurotransmission. The data support the general hypothesis that GABA modulates the circadian responses to light in a phase dependent manner, and may participate in entrainment to light-dark cycles by influencing the relative responsiveness to light in the early and late subjective night. PMID- 7772792 TI - Photoperiodic effects on tumor development and immune function. AB - Seasonal changes in adaptations associated with winter coping strategies have been frequently studied. Central among the suite of energy-saving, winter-coping strategies is the suspension of reproductive activities. The inhibition of reproduction by nontropical rodents is mediated by daylength changes. Although balanced annual energy budgets are critical, survival and subsequent reproductive success also require avoiding predators, illness, and early death. Because the stressors of winter could lead to suppressed immune function, we hypothesized that animals should have evolved survival strategies involving immunoenhancement. Short daylengths provide a predictive cue to individuals that could be used to enhance immune function in advance of stress-induced immunosuppression. In Experiment 1, adult female deer mice (Peromyscus maniculatus) were housed in either long (LD 16:8) or short (LD 8:16) days for 8 weeks, then injected with the chemical carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA) dissolved in dimethyl sulfoxide (DMSO) or with the DMSO vehicle alone. Animals were evaluated weekly for 8 weeks after injection. None of the animals treated with DMSO developed tumors in any of the experiments. Nearly 90% of the long-day deer mice injected with DMBA developed squamous cell carcinoma. None of the short-day deer mice injected with DMBA developed tumors. Small lesions developed at the site of injection; short-day females had less severe lesions and healed faster than long day females. Immunoglobulin G (IgG) response to i.p. injection of sheep red blood cells (SRBC) did not differ photoperiodic conditions. The role of estrogens in the photoperiodic responses was evaluated in Experiment 2: Ovariectomized or sham ovariectomized deer mice received estradiol benzoate replacement therapy or a control procedure in long daylengths for 8 weeks prior to injection of DMBA or DMSO, then were monitored for 8 additional weeks. Females treated with DMBA developed tumors at the same rate, regardless of estrogen manipulation. Estrogen did not affect healing rates. In Experiment 3, female deer mice were injected with a slurry of microspheres that either contained bromocriptine or were empty. Suppression of prolactin with bromocriptine resulted in a decrease of tumor incidence from 55.6% to 24% in long-day females 8 weeks after injection with DMBA. Healing rates were not affected by prolactin manipulations. Silastic capsules that were filled with either melatonin or cholesterol were implanted into long-day female deer mice in Experiment 4; 8 weeks later, females received an injection of either DMBA or DMSO, then were monitored for 8 weeks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7772794 TI - Different phase responses of the two circadian oscillators in Gonyaulax. AB - Two circadian oscillators have been previously shown to exist in the unicellular alga Gonyaulax polyedra by virtue of different periods for two different rhythms, which occur under certain experimental conditions. Here we show that phase shifts in response to light pulses also differ for these two rhythms. The phase response curves (PRCs) for white or blue light pulses are similar in shape and amplitude, but are somewhat displaced in time and have a slightly larger delay portion for the aggregation rhythm, corresponding to the A oscillator. In contrast, the aggregation rhythm PRC for dark pulses in a red light background has a much larger amplitude than that for the bioluminescence rhythm (B oscillator). These results suggest that the light input mechanism of the B oscillator is mainly blue sensitive, whereas that of the A oscillator is sensitive to both red and blue light. This is supported by entrainment experiments: Dark pulses given as a skeleton 24-hr scotoperiod in a blue light background act as a strong zeitgeber for both oscillators. But if red light is used as background, there is bistability in the entrainment of the B oscillator, whereas the A oscillator is entrained to a definitive phase angle, regardless of the cells' prior phase of entrainment. Finally, the two oscillators can be differentially entrained with 22 hr T cycles using 3-hr dark pulses interrupting red light (19 hr), whereas both oscillators are entrained when the dark pulses interrupt blue light. PMID- 7772795 TI - Deriving a "phase response curve" from adjustment to simulated time zone transitions. AB - Thirty-eight subjects in groups of two to four have been subjected to simulated time zone transitions of 8 hr eastward, 8 hr westward, or 12 hr; all experiments have taken place in a temporal isolation unit, in which the light intensity during the waking periods was 250-300 lux. Circadian rhythms of rectal temperature have been used as a marker of the process of adjustment, the data being analyzed before (raw) and after "purification." Conventional results have been obtained, but when the data have been treated appropriately, they have produced a relationship between shift of the sleep-activity cycle and shift of the temperature rhythms that shows many characteristics of a phase response curve. Even though the factor or factors causing such adjustment are unknown, the results confirm that changes of a consonant set of "weak" zeitgebers is sufficient for entrainment to a new time zone to occur. PMID- 7772796 TI - Twenty-four-hour rhythms in relation to the natural photoperiod: a field study in humans. AB - The daily rhythms of salivary melatonin, salivary cortisol, and axillary body temperature were measured in nine healthy volunteers in midsummer, around the autumn equinox, and in midwinter, at a latitude of 60 degrees N. The aim was to find out whether these rhythms were dependent on variations of the natural daylength. The samples were collected every 2 hr during 24-hr periods in everyday conditions. The individual rhythms were characterized with the acrophase estimates of the best-fitting cosine curve models and with the half-rise and half decline times calculated from the raw data. The melatonin and cortisol rhythms were delayed significantly (about 1 hr) in midwinter as compared with summer and autumn. The most advanced rhythms were found in autumn. The shifts of the melatonin and cortisol rhythms could be explained as a result of the changes of natural illumination. The overt temperature rhythms did not differ significantly among the sampling months. The lack of seasonal patterns in temperature rhythms probably primarily reflected the socially determined rest-activity cycles of the subjects. PMID- 7772797 TI - Phase-amplitude resetting of the human circadian pacemaker via bright light: a further analysis. AB - We present here an analysis of strong, weak, and critical bright-light resetting trials in humans, and report not only phase but also amplitude data for the first time. For this analysis, an appropriate iterative smoothing procedure for phase transition curves is introduced, in which the data are sequenced so as to minimize the perpendicular distance from the data to the smoothed fit. From these smoothed data, we create polar phase-amplitude resetting maps (PARMs) in order to fully illustrate the effects of the resetting stimuli on both circadian amplitude and phase, and thereby to determine whether these resetting results can be described by a phase-only model or whether a phase-amplitude model is required. Our results indicate that a single 5-hr episode of bright light induces weak type 1 resetting of the human circadian pacemaker. Two cycles of exposure to the same stimulus on consecutive days induce critical resetting, in which significant amplitude reduction may be observed. A three-cycle stimulus induces strong type 0 resetting with different effects on circadian amplitude, depending on the initial phase of the stimulus application. When a three-cycle stimulus is centered near the nadir of the temperature cycle, large phase shifts are achieved via amplitude suppression. However, when this stimulus is centered away from the temperature nadir, smaller phase shifts are achieved in which both small increases and small decreases in circadian amplitude are observed. These data indicate that the human circadian pacemaker is not a simple, phase-only oscillator. Instead, a full description of human circadian resetting responses to light requires analysis of both phase and amplitude data--a finding that is consistent with a phase amplitude model of the circadian resetting mechanism. PMID- 7772798 TI - Sensitivity of the human circadian pacemaker to moderately bright light. AB - The aim of the present study was to evaluate the sensitivity of the human circadian pacemaker to the resetting effect of moderately bright light (approximately 1260 lux), and to assess the direct effect of such light exposure by comparison to a control group of subjects undergoing the same behavioral manipulations but with a similarly timed exposure to darkness instead of light. Endogenous circadian phase and amplitude were assessed in dim light (approximately 10-15 lux) before and after two consecutive series of three 5-hr exposures to approximately 1260 lux or to darkness (approximately 0.03 lux) in two different groups of young healthy men, using the constant-routine technique. The light or darkness exposure was centered 1.5 hr after the initial fitted endogenous temperature minimum and 12 hr opposite the newly scheduled midpoint of the sleep episode, in order to induce a phase advance in the light-exposed subjects. The phase of the endogenous circadian pacemaker was assessed by a dual harmonic regression model from core body temperature recorded every minute during constant routines. Urinary volume was measured at each micturition, subjective alertness every 20 min, and cognitive performance hourly. The endogenous circadian phase shifted to a significantly earlier time after each series of light exposures in the treatment group than it did in the control group (two-way analysis of variance for repeated measures: F = 67.91, p = 0.0001). The analysis of circadian curves of urine production, subjective alertness, and cognitive performance scores revealed that all variables maintained stable temporal relationships with the endogenous circadian temperature minimum--an indication that these rhythms shifted in the same direction and by an equivalent amount. Despite comparable behavioral schedules, including the timing of bedrest/sleep and social contacts, circadian temperature rhythm of control subjects free-ran under dim light conditions, indicating that moderately bright light exerted a direct biological effect on the human circadian pacemaker in the treatment group. The present study also demonstrated that light of approximately 1260 lux (which is of substantially lower intensity that the approximately 7000-12,000 lux used in prior experiments) produces robust phase advances of the endogenous circadian temperature rhythm, which has been shown to be an accurate marker of the output of the circadian pacemaker (Czeisler et al., 1989). These results support the hypothesis that the phase-shifting effect of light on the human circadian pacemaker has a strongly nonlinear relationship to illuminance levels, such that it is preserved despite marked reductions in light intensity. PMID- 7772799 TI - The nodS gene of Rhizobium tropici strain CIAT899 is necessary for nodulation on Phaseolus vulgaris and on Leucaena leucocephala. AB - Rhizobium tropici strain CIAT899 induces nitrogen-fixing nodules on the roots of a wide range of tropical legumes, including Phaseolus vulgaris and Leucaena leucocephala. Previously, a DNA region of the CIAT899 pSym plasmid containing the common nodulation genes nodABC and one of the nodD alleles was characterized (P. van Rhijn, B. Feys, C. Verreth, and J. Vanderleyden, J. Bacteriol. 175: 438-447, 1993). As reported here, the region immediately downstream of nodC contains the nodSU genes. The nucleotide sequence of these genes is presented. CIAT899 nodS and nodU mutants were constructed. The nodS mutant was completely deficient in nodulation on the host plants P. vulgaris and L. leucocephala. The nodU mutation caused a decrease in nodulation on Leucaena but resorted no effect on Phaseolus. Introduction of the CIAT899 nodABCSU region in R. etli CE-3, a strain that only nodulates P. vulgaris, caused an extension of the host range of strain CE-3 to L. leucocephala. PMID- 7772800 TI - Virus-induced gene expression for enzymes of ethylene biosynthesis in hypersensitively reacting tobacco. AB - A full-length cDNA clone (cEFE-26) encoding ethylene-forming enzyme (EFE) was isolated from a cDNA library, prepared from leaves of tobacco mosaic virus (TMV) infected tobacco cultivar Samsun NN. The cDNA clone encodes a protein with 90% amino acid sequence similarity to established EFEs of tomato and other plants. By using cEFE-26 cDNA and the insert from cDNA clone pACC13 (B. A. Bailey, A. Avni, N. Li, A. K. Mattoo, and J. D. Anderson, Plant Physiol. 100:1615-1616, 1992) encoding tobacco 1-aminocyclopropane-1-carboxylic acid synthase as probes, it was established that tobacco contains small gene families for these proteins. Furthermore, RNA blot analyses indicated that transcript levels in leaves for the two ethylene pathway genes were elevated after infection with TMV. The results are discussed in relation to a possible signalling role of ethylene in induced resistance and gene expression for pathogenesis-related proteins. PMID- 7772801 TI - Mutational analysis of the coat protein gene of brome mosaic virus: effects on replication and movement in barley and in Chenopodium hybridum. AB - The coat protein (CP) open reading frame (ORF) of brome mosaic virus (BMV) has been mutated to study host-related CP functions in barley, a systemic host, and in Chenopodium hybridum L. which supports both local lesion formation and systemic spread of BMV. To test the role of the N-terminal region of CP, mutants C1 to C3, which synthesized the CP lacking first seven amino acids, and mutant D1, which had Trp 22 and Thr 23 replaced with Phe-Gly-Ser, were generated. C1 to C3 inhibited virus systemic spread in C. hybridum but not in barley while D1 only reduced virus accumulation in noninoculated leaves of C. hybridum. More internal CP regions were tested by mutation of Lys 63 to Leu (mutant SP3) and Lys 129 to Arg (mutant SP1). SP1 behaved similarly to C1 to C3 while SP3 similarly to D1. In addition, SP3 reduced concentrations of RNA3 and RNA4 in both hosts. Apparently, various CP regions differentially affect, either directly or indirectly, virus translocation in different hosts, suggesting both the CP and host factors to be important for virus spread. Larger deletions in the CP ORF (mutants BB4 and SX1) or a decrease of CP production by using a frameshift mutant C, inhibited virus systemic spread in both hosts, and delayed the appearance of smaller local lesions on C. hybridum. Thus, the CP is not required for cell-to-cell movement but is required for systemic translocation of BMV. PMID- 7772802 TI - Purification and immunological characterization of toxic components from cultures of Pyrenophora tritici-repentis. AB - To facilitate the genetic analysis of pathogenicity in the wheat-Pyrenophora tritici-repentis interaction, a host-selective toxic protein, designated ToxA, was purified from culture filtrates of this fungus. ToxA was shown to be a 13.2 kDa heat-stable protein which induced visible necrosis in sensitive wheat cultivars at an average minimum concentration of 60 nM. Polyclonal antibodies raised against ToxA were shown by Western analysis and indirect immunoprecipitation to be specific for this protein. Bioassays of immunoprecipitated protein and ToxA protein eluted from polyacrylamide gels indicated that ToxA protein is the toxic agent. Other less abundant necrosis inducing components that are chromatographically and immunologically distinct from ToxA were also detected in culture filtrates of P. tritici-repentis. These components were found in cationic and anionic protein fractions and, like ToxA, induced cultivar-specific necrosis. PMID- 7772803 TI - Characterization of avrE from Pseudomonas syringae pv. tomato: a hrp-linked avirulence locus consisting of at least two transcriptional units. AB - Cosmid clone pPT10E9 from Pseudomonas syringae pv. tomato caused P. s pv. glycinea to elicit the HR on leaves of all tested soybean cultivars. The avirulence function of pPT10E9, called avrE, occurred on an 11.3-kb DNA fragment located immediately adjacent to the P. s. pv. tomato hrp gene cluster. Tn3-gus saturation mutagenesis of the avrE locus and adjacent DNA revealed at least four transcriptional units occurring immediately adjacent to the hrpRS locus that were all regulated in a manner similar to hrp genes (induced only in minimal induction media or in planta and required the hrpL and hrpRS loci for expression). Transcriptional units III and IV, but not II or V, were required for avrE function. P. s. pv. tomato DC3000 carrying mutations in each of the four transcripts retained full virulence on tomato leaves and elicited the HR on tobacco and soybean plants. This was unlike strain PT23, where mutation of avrE greatly decreased virulence on tomato leaves. The promoter regions for three of the investigated transcriptional units contained a consensus sequence occurring in the promoter regions of several other P. syringae avirulence and hrp genes. The promoter region of transcriptional unit IV, required for avrE function, did not contain such a sequence, but included an element which may function as a sigma-54 promoter. Introduction of the cloned P. s. pv. tomato avrE locus into five other P. syringae pathovars did not cause them to elicit the HR on their normal host plants. PMID- 7772804 TI - Transgenic tobacco plants expressing a truncated form of the PAMV capsid protein (CP) gene show CP-mediated resistance to potato aucuba mosaic virus. AB - Four constructs of the potato aucuba mosaic virus (PAMV) coat protein (CP) gene were engineered for expression in tobacco plants: The full-length CP sequence (FL CP), two truncated forms--one at the N terminus (46 amino acid residues are deleted) (NT138), one in the conserved core portion (86 amino acids deleted) (CT258) of the gene--and an antisense RNA construct. These constructs were introduced into tobacco plants (Nicotiana tabacum) via Agrobacterium tumefaciens mediated transformation. The plants transformed with the NT138 and FL CP constructs produced the mRNAs and proteins from the respective transgene. Transformants with the CT258 construct produced the transgenic mRNA, but the modified CP was not detected in the 20 different transformants tested. Transgenic R0 and R1 tobacco plants expressing the full-length, CT258, and the antisense constructs exhibited protection to PAMV infection and a delay in symptom development when inoculated with 0.1 and 0.5 microgram/ml of purified PAMV. Transgenic plants expressing the NT138 construct did not confer any detectable protection to PAMV infection. These results suggest that an engineered coat protein mediated resistance (CPMR) can be obtained from a CP gene truncated in its core region. The role of the N-terminal domain of the CP in the CPMR of PAMV and the implication of either the RNA or the protein in the protection is discussed. PMID- 7772805 TI - Antimicrobial peptides. PMID- 7772806 TI - Resistance to tospoviruses in Nicotiana benthamiana transformed with the N gene of tomato spotted wilt virus: correlation between transgene expression and protection in primary transformants. AB - Nicotiana benthamiana was transformed with the nucleoprotein (N) gene of an Italian isolate of tomato spotted wilt virus (TSWV). Forty-five T1 primary transformant lines were analyzed for the expression of N protein and for resistance to TSWV and three other tospoviruses: impatiens necrotic spot virus (INSV), groundnut bud necrosis virus (GBNV), and groundnut ringspot virus (GRSV). Thirteen of these lines were further characterized. Resistance to all TSWV isolates tested was found in two lines. The expression of the transgene (N mRNA) was lower in these resistant lines than in any of the susceptible lines, and the transgene N protein was either absent or present below detectable levels. These lines were susceptible to the other tospoviruses tested, but they developed symptoms milder than controls when inoculated with GRSV. Some of the lines producing high levels of N protein showed delays (of 2-3 weeks) in symptom expression with at least one of the TSWV isolates tested and symptom delay or attenuation with INSV or GRSV (or both). From our results it appears that high expression of TSWV N protein retards, in some cases, disease development by TSWV and INSV. In contrast, the lack of detectable expression of the transgenic N protein, accompanied by limited production of N transcripts, conferred TSWV specific resistance. PMID- 7772807 TI - Broad resistance to tospoviruses in transgenic tobacco plants expressing three tospoviral nucleoprotein gene sequences. AB - Transgenic tobacco plants have been obtained expressing nucleoprotein (N) gene sequences of three different tospoviruses known to affect vegetable crops: tomato spotted wilt virus (TSWV), tomato chlorotic spot virus (TCSV), and groundnut ringspot virus (GRSV). The chimeric plant transformation vector used comprised the three viral N gene sequences, each with a copy of the CaMV 35S promoter and the nos terminator. Despite the high levels of homology between the different N gene sequences (74-82%) and the presence of repeated promoter and terminator sequences in this construct, unrearranged copies of this triple N gene construct were stably maintained in both Escherichia coli and Agrobacterium tumefaciens plasmids used during the cloning process, as well as in several generations of transgenic tobacco plants. A transgenic tobacco line was obtained that exhibited high levels of resistance to all three tospoviruses, showing the possibility of producing transgenic plants with a broad resistance to tospoviruses by introducing tandemly cloned viral N gene sequences. DNA analysis of this transgenic plant line shows that the multivirus resistance trait is confined to a single genetic locus, which is very convenient for further breeding purposes. PMID- 7772808 TI - Nucleotide sequence of a pectate lyase structural gene, pel1 of Erwinia carotovora subsp. carotovora strain 71 and structural relationship of pel1 with other pel genes of Erwinia species. AB - Of the various exoproteins secreted by Erwinia carotovora subsp. carotovora strain 71, Pel1 is the major pectate lyase species with tissue macerating activity. Nucleotide sequencing of a 2.2-kb pel1+ DNA segment revealed a 1,122 base pair open reading frame which could encode pre-Pel1 of 374 amino acid residues. A signal peptide of 22 amino acid residues is present within the NH2 terminal region of pre-Pel1. Transcription of pel1 was initiated at the guanine residue 111 base pairs upstream of the start codon. Consensus sequences for the binding of KdgR, a negative regulatory factor known to control some of the E. chrysanthemi pectinases, flank the promoter of pel1. Although pel1 belongs to the pelBC family, it is more closely related to the pel genes of E. carotovora than to the pelBC genes of E. chrysanthemi. PMID- 7772809 TI - Imaging and intervention in abdominal emergencies. AB - While plain abdominal radiographs retain an essential place in acute abdominal emergencies, the dramatic advances in ultrasound, computed tomography and magnetic resonance imaging witnessed over the past two decades have revolutionized the practice of emergency medicine. Cross-sectional imaging techniques now play a key role in evaluating patients with abdominal emergencies, and allow confident diagnoses to be made in an ever increasing proportion of these patients. Unnecessary laparotomies are now uncommon, and a wide array of interventional radiological techniques can be used to treat abdominal emergencies without surgery. PMID- 7772810 TI - 3-D reconstruction of hepatic neoplasms: a preoperative planning procedure. AB - Three-dimensional display of intrahepatic vascular structures, tumour(s) and liver surface offers the possibility of perceiving the complex individual anatomy in a coherent fashion. Since this presentation of anatomical structures can be varied at will, the resulting interactive dynamic display of the 3-D data sets can be considered an example of Virtual Reality; the surgeon experiences the interactive 3-D display as a realistic presentation of the patient's surgical anatomy. Three-dimensional display offers the possibility of planning a specific resection in detail, tailored to the individual anatomy. The benefits and problems of various surgical approaches can be worked out in detail, and potential hazardous phases in the operation can be anticipated, thus minimizing unexpected complications. However, because the generation of detailed 3-D renderings takes considerable time investment by an experienced operator it is important to select patients, in whom such an effort is warranted. In our experience, 3-D display of the liver is most likely to be of benefit in the presence of central tumours, or if segmental resections are considered. PMID- 7772811 TI - Cross-sectional imaging of the pancreas. AB - CT is the primary modality for the evaluation of patients with pancreatic disease. A number of pitfalls can occur in interpretation of the scans, but most can be avoided by using state-of-the-art scanners and dynamic contrast enhancement techniques and by recognizing normal anatomic variants. However, in other cases, CT may show only nonspecific findings and a correct diagnosis can be reached only by utilization of additional imaging techniques or guided FNAB. PMID- 7772812 TI - Current applicability of duplex Doppler ultrasonography in pancreatic head and biliary malignancies. AB - In most patients with a pancreatic head carcinoma or a cholangiocarcinoma of the liver (Klatskin tumour) US is the first imaging modality. Tumour detection using US can exceed that of CT. For small tumours, endosonography or ERCP is recommended. Enlarged lymph nodes are not a major diagnostic parameter, because a reliable differentiation between reactive and malignant lymph nodes is generally not possible. Very tiny liver and peritoneal metastases are missed by the current imaging modalities including US and only detectable by laparoscopy and/or laparoscopic US. Tumour involvement of the portal venous system is an important determinant for irresectability which can often be assessed by duplex Doppler US obviating invasive or expensive imaging modalities. In pancreatic head carcinoma an abnormal pulsed Doppler signal is highly suspicious for involvement of the portal venous system. However, a normal pulsed Doppler signal does not exclude involvement at all. In Klatskin tumour, Doppler US had an accuracy of 91% compared with surgical findings in predicting portal venous involvement. In most cases of pancreatic head carcinoma or Klatskin tumour, US can assess irresectability. However, assessment of curative resectability in these tumours remains a problem. PMID- 7772813 TI - Imaging and intervention in patients with acute right upper quadrant disease. AB - Because of the high diagnostic yield, its widespread availability and the possibility of bedside examinations, US has become the imaging modality of choice in patients with acute right upper quadrant pain caused by inflammatory disorders such as liver abscesses, acute cholangitis and acute cholecystitis. Computed tomography (CT) can be reserved for more complex cases. US, often in combination with fluoroscopy, is also widely used to control interventions. In patients with liver abscesses the therapeutic strategy is determined by the size of the abscess, its uni- or multifocal presentation and the causative micro-organisms cultured after diagnostic percutaneous aspiration. Small-sized pyogenic abscesses (< 3 cm), most fungal and amoebic abscesses can be treated medically. Large-sized pyogenic abscesses should be drained percutaneously and can be cured in 75-90%. Surgery should be restricted to patients with prolonged sepsis after percutaneous drainage and patients with infected pre-existing hepatic lesions. In patients with acute cholangitis drainage of the infected bile is essential. Invasive imaging such as percutaneous or endoscopic cholangiography procedures such as nasobiliary drainage, stent placement and sphincterotomy has decreased mortality rates dramatically. Percutaneous drainage should be considered in patients in whom endoscopic procedures fail. Surgery may have a place in the treatment of bile duct obstruction which causes cholangitis. In patients with suspected acute cholecystitis, imaging modalities such as cholescintigraphy and CT can be reserved for patients with inconclusive sonographic studies and more complex cases. The contribution of percutaneous gallbladder aspiration and culture to diagnose acute cholecystitis seems limited. Percutaneous cholecystostomy is an effective procedure with a low morbidity and mortality for high-risk patients. The drainage catheter in the gallbladder does not interfere with cholecystectomy at a later stage in patients with calculous cholecystitis. In most patients with acalculous cholecystitis, percutaneous cholecystectomy provides a definitive treatment. PMID- 7772814 TI - Imaging and intervention in patients with acute right lower quadrant disease. AB - US using graded compression plays a central role in the diagnostic work-up of acute right lower quadrant disease, but its results should always be integrated with clinical data and results of other possible radiological examinations. Direct US visualization of an inflamed appendix is solid proof of appendicitis. Pitfalls are secondary enlargement in perforated peptic ulcer, caecal carcinoma or Crohn's disease. If a normal appendix is visualized in its full length, appendicitis can be excluded. However, this is rarely the case. In practice, the only means to exclude appendicitis is to demonstrate an alternative condition, which in most cases is possible by US alone. Concomitant adynamic ileus is a valuable US finding. Abscesses related to appendicitis, Crohn's disease and colonic carcinoma respond well to percutaneous drainage, which is technically possible in 95% of cases. Some of these abscesses evacuate spontaneously to neighbouring bowel. For abscesses due to caecal diverticulitis spontaneous evacuation to the caecal lumen is the rule. For indication and drainage strategy, integration of US, CT and clinical data are indispensable. The use of US in right lower quadrant disease will not only lead to a strong improvement of diagnostic accuracy, but also to better understanding of the incidence and natural course of various conditions such as abortive appendicitis, appendiceal abscess, caecal diverticulitis, bacterial ileocaecitis and right-sided segmental infarction of the omentum. PMID- 7772815 TI - Radiological intervention in upper and lower gastrointestinal bleeding. AB - The role of angiography in acute upper GI tract bleeding is less a diagnostic than a therapeutic one because it provides a guide to selective embolization of either the left gastric artery, or the gastroduodenal artery and its two principal branches, the pancreaticoduodenal and the right gastroepiploic artery. Angiographic catheter techniques may also provide substantial diagnostic and therapeutic support for the management of acute lower GI bleeding from a variety of bleeding sources. The advantages are minimal invasion and relatively low risk. The intermittent nature of GI bleeding often interferes with the ability of angiography to demonstrate the source of bleeding. However, at times angiographic techniques provide the only reasonable means of localizing and controlling bleeding. PMID- 7772816 TI - Current applicability of scintigraphic methods in gastroenterology. AB - Patients are often referred for evaluation of a wide range of GI complaints including dysphagia, abdominal pain, bloating, nausea, constipation or diarrhoea. Many are diagnosed with 'functional' disease when endoscopy or conventional radiological studies fail to identify an anatomic cause for the patient's symptoms. In such cases nuclear medicine offers non-invasive methods for objectively demonstrating disease involving different areas of the gastrointestinal tract. Increasingly scintigraphy is playing a primary role in the evaluation of patients with suspected acute cholecystitis, active gastrointestinal bleeding, gastroparesis, and small and large bowel motility disorders. In addition, it supplements other studies when results are inconclusive in diagnosing oesophageal dysmotility, gastro-oesophageal reflux, acalculous cholecystitis, and postoperative complications of gastrointestinal surgery. PMID- 7772817 TI - Cross-sectional imaging of the liver. AB - The liver can be affected by a number of conditions that can involve the liver focally or diffusely. CT and MRI are reliable techniques for demonstrating these abnormalities, and both imaging tools play an important role in the clinical evaluation of the patients. However, each technique provides different information, and the most appropriate cross-sectional technique used should be tailored in each instance to the individual patient situation. PMID- 7772818 TI - Antitumor active fucoidan from the brown seaweed, umitoranoo (Sargassum thunbergii). AB - Neutral and acidic polysaccharides and their protein complexes were fractionated and purified from the brown seaweed umitoranoo (Sargassum thunbergii) by fractional extraction, iron-exchange chromatography, and gel filtration. Thirty one polysaccharide fractions were obtained and tested for antitumor activity in mice with Ehrlich carcinoma transplanted i.p. Two of the fractions, GIV-A ([alpha]25D -127 degrees and mol. wt., 19,000) and GIV-B ([alpha]25D -110 degrees and mol. wt., 13,500) had such activity. On the basis of chemical and spectral analyses, these compounds were found to be a fucoidan or L-fucan containing approx. 30% sulfate ester groups per fucose residue, about 10% uronic acid, and less than 2% protein. PMID- 7772819 TI - Antitumor-active heteroglycans from niohshimeji mushroom, Tricholoma giganteum. AB - Water-soluble polysaccharide FI and water-insoluble polysaccharides FII, FIII-1, and FIII-2 were obtained from fruiting bodies of Tricholoma giganteum. Polysaccharides were further fractionated by ion-exchange chromatography, gel filtration, and affinity chromatography. The 24 polysaccharide fractions obtained were examined for their antitumor effect on Sarcoma 180 implanted in mice. The following antitumor-active polysaccharides were identified: FIo-a, a mixture of alpha-D-glucan and xyloglucomannan with an average molecular weight of 1.6 x 10(6); FA-1, a beta-D-glucan containing 1% protein and with a molecular weight of 4.0 x 10(4); FII-1, a (1-->3)-beta-D-glucan containing 7.8% protein, with a molecular weight of 5.2 x 10(4); FIII-1-b, a protein-polysaccharide complex (ratio, 37.5:62.5, w/w), with a molecular weight of 6.8 x 10(4) and with xylose, galactose, mannose, and glucose in the polysaccharide moiety (proportions of 8.9:14.9:29.3:46.9 by weight), and FIII-2-a, b, and c, three (1-->6)-beta-D glucosyl-branched (1-->3)-beta-D-glucans with a molecular weight from 2.6 x 10(5) to 4.1 x 10(5) and containing small amounts of xylose and galactose and 3.5-8.3% protein. PMID- 7772820 TI - Oxidation of ethylene glycol and glycolic acid by glycerol oxidase. AB - A glycerol oxidase from Aspergillus japonicus oxidized ethylene glycol to glyoxal by the same reaction pathway as alcohol oxidases from methanol yeast. The optimum pH and temperature for the oxidation of ethylene glycol were around 7.0 and 40 degrees C, respectively. Those of glycolaldehyde were similar to those of ethylene glycol. The apparent Kms for ethylene glycol and glycolaldehyde were 195 and 48.8 mM, respectively. The maximum velocities for ethylene glycol and glycolaldehyde were 89.1 and 62.2 mumol/min/mg of protein, respectively. Glycerol oxidase also oxidized glycolic acid, which is not oxidized by the alcohol oxidases, to glyoxylic acid like glycolate oxidases from green plants, and the apparent Km and Vmax for glycolic acid were 114 mM and 2.68 mumol/min/mg of protein, respectively. The glycerol oxidase was applicable to the production of glyoxal and glyoxylic acid. PMID- 7772821 TI - Nucleotide sequence analysis of the carbomycin biosynthetic genes including the 3 O-acyltransferase gene from Streptomyces thermotolerans. AB - A 3.2-kb DNA fragment of the carbomycin biosynthetic region including the 3-O acyltransferase gene (acyA) from Streptomyces thermotolerans was sequenced, and four ORFs were found in the fragment. The second ORF, designated ORF-A, was transcribed in the opposite direction to the other three ORFs. The first ORF was identified as carA, a gene for carbomycin resistance. The amino acid sequence of ORF-A was homologous to proteins of the cytochrome P-450 family. Streptomyces lividans transformed with pCB20, in which ORF-A was subcloned, epoxidized carbomycin B at its C-12, 13 positions, thus producing carbomycin A. The third ORF, the amino acid sequence of which showed a homology to macrolide antibiotics O-acyltransferases was identified as acyA. The last ORF (ORF-B), which starts just 3 bp downstream from the TGA termination codon of acyA, was thought to be a carbomycin 4-O-methyltransferase gene, because the amino acid sequence deduced from ORF-B showed high homology to a putative midecamycin 4-O-methyltransferase encoded on mdmC. PMID- 7772822 TI - Efficient production and purification of extracellular 1,2-alpha-L-fucosidase of Bacillus sp. K40T. AB - When Bacillus sp. K40T was cultured in the presence of L-fucose, 1,2-alpha-L fucosidase was found to be produced specifically in the culture fluid. The enzyme was purified to homogeneity from a culture containing only L-fucose by chromatography on hydroxylapatite and chromatofocusing. The molecular weight of the enzyme was estimated to be 200,000 by gel filtration on Sephadex G-200. The enzyme was optimal at pH 5.5-7.0 and was stable at pH 6.0-9.0. The enzyme hydrolyzed the alpha-(1-->2)- L-fucosidic linkages in various oligosaccharides and glycoproteins such as lacto-N-fucopentaose (LNF)-I 2) O-beta-D-galactose-(1-->3)-N-acetyl-O-beta-D- glucosamine-(1-->3)-O-beta-D galactose-(1-->4)-D-glucose>, porcine gastric mucin, and porcine submaxillary mucin. The enzyme also acted on human erythrocytes, which was confirmed by the hemagglutination test using Ulex anti-H lectin. The enzyme did not hydrolyze alpha-(1-->3)-, alpha-(1-->4)- and alpha-(1-->6)-L-fucosidic linkages in LNF-III 4)[O- alpha-L-fucose-(1-->3)-]-N-acetyl-O-beta-D glucosamine-(1-->3)-O-beta-D- galactose-(1-->4)-D-glucose>, LNF-II 3)[O-alpha-L- fucose-(1-->4)-]-N-acetyl-O-beta-D-glucosamine-(1- >3)-O-beta-D- galactose-(1-->4)-D-glucose> or 6-O-alpha-L-fucopyranosyl-N acetylglucosamine. PMID- 7772824 TI - Inhibitory activity of 8-azadecalin derivatives towards 2,3 oxidosqualene:lanosterol cyclases from baker's yeast and pig's liver. AB - The inhibitors of 2,3-oxidosqualene:lanosterol cyclase were investigated by comparative studies between pig's liver and Baker's yeast. The fundamental skeleton of the inhibitors was 8-azadecalin. To the nitrogen atom, an isoprenoid like chain [nerylacetone (Z-form), geranylacetone (E-form) or its hydrogenated form] was attached by the reaction of reductive amination with NaCNBH3. Among the three forms, the Z-isomer was the most potent inhibitors toward both the pig's liver and yeast cyclases. To examine the effect of carbon chain length (lipophilicity), various fatty acids (C6-C18) were appended to the 8-azadecalin derivatives. Strong inhibitory activity was observed for those compounds having carbon chains around C12. Interestingly, the amide compounds (not the carbocationic intermediate) exhibited remarkably strong inhibition toward the liver cyclase, whereas they had an insignificant effect on the yeast cyclase (about 10(2)-fold less active). The yeast cyclase needed the amine functionality (carbocationic intermediate), which was prepared by using LiAlH4 from the corresponding amides, to exhibit potent inhibition. We found that N-dodecyl-8-aza 4,4,10 beta-trimethyl-trans-decal-3 beta-ol (7i) was the most potent inhibitor (IC50 = 1 microM) toward the yeast cyclase amongst any known material. Kinetic studies showed that the inhibition pattern was dependent only on whether the side chains on the 8-azadecalin were linear or branched; the compounds having isoprenoid-like chains were non-competitive inhibitors, while those having linear hydrocarbon chains (amides or amines) were competitive inhibitors. PMID- 7772823 TI - Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats. AB - The effects of isorhamnetin, rhamnetin and quercetin on the serum and liver cholesterol concentrations, liver lipoperoxide (thiobarbituric acid-reactive substances: TBARS) content, and antioxidative enzyme activities were examined with rats fed on cholesterol-enriched and cholesterol-free diets. The total serum cholesterol of those rats fed with the cholesterol-enriched diet was decreased by feeding each all these flavonoids. The total liver cholesterol concentration and TBARS content in the rats fed with the cholesterol-free diet were decreased by feeding isorhamnetin, rhamnetin and quercetin. The activities of liver superoxide dismutase and catalase were almost unaffected by feeding these flavonoids. These results, the in vitro antioxidative activities of isorhamnetin, rhamnetin and quercetin, and the activities of these flavonoids in suppressing the generation of the superoxide anion in vitro suggest the possibility that the lower liver TBARS content in those rats fed on the cholesterol-free diet with added flavonoids is ascribable in part to the direct antioxidative and superoxide anion generation-suppressing activities of flavonoids and/or their metabolites absorbed from the gastrointestinal tract. PMID- 7772825 TI - Cloning, purification, and properties of a cofactor-independent glutamate racemase from Lactobacillus brevis ATCC 8287. AB - A glutamate racemase gene of Lactobacillus brevis ATCC 8287 was cloned into Escherichia coli TM93 by the phenotypic complementation of a phosphoenolpyruvate carboxylase deficiency on minimum agar medium containing D-glutamate. The gene was localized to a 1.4-kb HindIII-EcoRI DNA fragment and the total nucleotide sequence of the fragment was analyzed. The gene has typical promoter and SD sequences which appeared to function in E. coli. The deduced amino acid sequence of the enzyme had 276 amino acids and the molecular weight was calculated as 29,426. Two cysteine residues and their surrounding regions of the enzyme are homologous to those of other cofactor-independent racemases. The glutamate racemase was purified from recombinant E. coli to homogeneity and characterized. The enzyme required no cofactors for the activity, and retained its activity even in 2 M (300 g/l) L-glutamate. PMID- 7772826 TI - Transgalactosylation catalyzed by alpha-galactosidase from Candida guilliermondii H-404. AB - The thermostable alpha-galactosidase from Candida guilliermondii H-404 synthesized self-transfer products in the absence of a suitable acceptor. The main self-transfer product, using melibiose as a donor substrate, was O-alpha-D galactosyl-(1,6)-O-alpha-D-galactosyl-(1,6)-D-glucose. This enzyme had a wide acceptor specificity. D-Glucose, D-galactose, maltose, maltitol, and 1,4 butandiol were the most effective acceptors in the transgalactosylation catalyzed by this enzyme. The enzyme could also transfer alpha-galactosyl residues to pentoses (L-arabinose, D-xylose, and D-ribose) and methyl pentoses (D-fucose and L-rhamnose). The main transfer products to lactose, maltose, and sucrose as acceptors were identified as O-alpha-D-galactosyl-(1,6)-O-beta-D-galactosyl-(1,4) D-glucose, O-alpha-D-galactosyl-(1,6)-O-alpha-D-glucosyl-(1,4)-D-glucose, and O alpha-D-galactosyl-(1,6)-O-alpha-D-glucosyl-(1,2)-beta-D-fructoside (raffinose), respectively. PMID- 7772828 TI - Purification and characterization of extracellular alginate lyase from Enterobacter cloacae M-1. AB - An alginate lyase from the culture supernatant of Enterobacter cloacae M-1 was purified by ammonium sulfate precipitation, cation-exchange chromatography (SP Toyopearl), and gel filtration (Ultrogel AcA44). The final preparation thus obtained showed a single band on SDS-PAGE. The purified enzyme had the molecular weight of 38,000 and 32,000 by SDS-PAGE and gel filtration, respectively. The pI of the enzyme was 8.9. The optimum pH and temperature for the enzyme reaction were around 7.8 and 30 degrees C, respectively. The enzyme was unstable on heating. EDTA completely inhibited the enzyme activity, but the activity was completely restored by the treatment with CaCl2. The enzyme was specific for poly guluronate and produced several kinds of unsaturated oligomers from the gluluronate. This suggested that the enzyme could be classified as an endo poly guluronate lyase. PMID- 7772827 TI - Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins. AB - The interaction of IL-4, IL-5, and free bile acids with the immunoglobulin production by mouse spleen lymphocytes was studied to examine their immunoregulatory activity. In the absence of lipopolysaccharide (LPS), IL-4 enhanced the IgE and IgG production significantly and the IgA production weakly, but not the IgM production. On the other hand, IL-5 had an inhibitory tendency on the IgE and IgA production, though not significantly. In the presence of LPS, both IL-4 and IL-5 significantly enhanced the IgE production by mouse splenic lymphocytes. When the lymphocytes were cultured with the physiological concentration of free bile acids (10 microM) and LPS for 3 days, chenodeoxycholic acid inhibited the IgE production, but cholic and deoxycholic acids did not. In the presence of IL-4 or IL-5, these bile acids cancelled the stimulatory effects of interleukins and rather significantly inhibited the IgE production. These results suggest that these free bile acids act as an anti-allergic agent. PMID- 7772829 TI - A system for sialic acid transfer by colominic acid and a sialidase that preferentially hydrolyzes sialyl alpha-2,8 linkages. PMID- 7772830 TI - Selective incorporation of n-3 and n-6 unsaturated fatty acids into animal cell phospholipids. AB - The selective incorporation of n-3 and n-6 unsaturated fatty acids into phospholipids was investigated by changing the ratio of n-3 unsaturated fatty acids against n-6 unsaturated fatty acids in the medium where Chinese hamster V79 R cells were grown. Unsaturated fatty acids with lower degrees of unsaturation were abundantly incorporated into phosphatidylcholine independently of n-3 and n 6. Unsaturated fatty acids with higher degrees of unsaturation were more predominantly incorporated into phosphatidylethanolamine. When the difference in the numbers of double bond between unsaturated fatty acids was more than two, the unsaturated fatty acids with a higher degree of unsaturation was more selectively incorporated into phosphatidylethanolamine than the unsaturated fatty acids with a lower degree of unsaturation. By the analysis of molecular species, n-3 and n-6 unsaturated fatty acids with higher degrees of unsaturation were incorporated competitively into phosphatidylethanolamine. Finally, docosahexaenoic acid was incorporated into diacyl phosphatidylethanolamine more selectively than the other unsaturated fatty acids. PMID- 7772831 TI - Purification and characterization of two chitinases from the leaves of pokeweed (Phytolacca americana). AB - Two chitinases, designated PLC-A and PLC-B, were purified from the leaves of pokeweed (Phytolacca americana) using DEAE-cellulose column chromatography followed by gel filtration on Sephadex G-75, hydrophobic column chromatography, and ion-exchange FPLC. PLC-A and PLC-B are acidic and basic proteins having molecular masses of 25 and 29 kDa, and isoelectric points of 3.7 and 9.5, respectively. On the basis of their partial amino acid sequences, it was seen that PLC-A and PLC-B belong to class II and class III chitinases, respectively. The optimal pH of PLC-A toward glycolchitin is pH 4.5 and hydrolyzed (GlcNAc)4 into 2(GlcNAc)2, and (GlcNAc)5-6 into (GlcNAc)2 and (GlcNAc)3. on the other hand, PLC-B has two optimal pHs at 3 and 7 toward glycolchitin and hydrolyzed (GlcNAc)5 into GlcNAc and (GlcNAc)4, and (GlcNAc)6 into GlcNAc, (GlcNAc)2, and (GlcNAc)4. PMID- 7772832 TI - Phosphatidylinositol-3 kinase in fission yeast: a possible role in stress responses. AB - A DNA fragment coding for a part of a putative phosphatidylinositol 3 kinase was cloned from Schizosaccharomyces pombe by cross-hybridization with Saccharomyces cerevisiae VPS34 gene, a yeast homologue of mammalian PI-3 kinase. The clone contained an open reading frame of 797 amino acids but lacked the initiation codon, ATG. The predicted amino acid sequence was homologous to those of S. cerevisiae VPS34 and mammalian PI-3 kinase genes. Disruption of the gene resulted in extremely low levels of PI-3-P and higher levels of PI-4-P, supporting the idea that the gene codes for the PI-3 kinase of S. pombe. The disruptants harbored large vacuoles and were sensitive to stresses such as high temperature or high concentration of monovalent and divalent cations. PMID- 7772833 TI - Purification and characterization of three mitogenic lectins from the roots of pokeweed (Phytolacca americana). AB - Three mitogenic lectins, designated PL-A, PL-B, and PL-C, were purified from the roots of pokeweed (Phytolacca americana) using Q-Sepharose column chromatography followed by gel filtration on Sephadex G-75, hydrophobic chromatography on Butyl Toyopearl, and FPLC on a Mono-Q column. PL-A, PL-B, and PL-C are acidic proteins having isoelectric points of 4.35 and their apparent molecular masses were 22, 48, and 21 kDa by SDS-polyacrylamide gel electrophoresis in the presence of 2 mercaptoethanol, respectively. The three lectins have similar amino acid compositions rich in half-cystine and similar N-terminal sequences, indicating that they are homologous proteins. Identical sequences of N-terminal regions and six corresponding tryptic peptides in PL-A and PL-B suggested that PL-A may be an N-terminal half fragment of PL-B. Although all of three lectins have mitogenic activities, PL-B is a mitogenic lectin with the most potent hemagglutinating and mitogenic activities, and PL-C has almost no hemagglutinating activity. PMID- 7772834 TI - Role of basic and acidic fragments in delicious peptides (Lys-Gly-Asp-Glu-Glu-Ser Leu-Ala) and the taste behavior of sodium and potassium salts in acidic oligopeptides. AB - The role of the acidic fragment (Asp-Glu-Glu) in delicious peptides was investigated in detail by using the Na+ or K+ salts of acidic oligopeptides so that amount of Na+ or K+ intake of peptides composed of acidic amino acids could be varied by changing their sequences. The taste of these peptides was confirmed to vary with Na+ or K+ intake. Additionally, in order to study the role of basic (Lys-Gly) and acidic (Asp-Glu-Glu) fragments in delicious peptides for producing the taste, five delicious peptide analogs, Ser-Leu-Ala-Lys-Gly-Asp-Glu-Glu, Ser Leu-Ala-Asp-Glu-Glu-Lys-Gly, Lys-Gly-Ser-Leu-Ala-Asp-Glu-Glu, Lys-Gly-Asp-Glu Glu, and Glu-Glu-Asp-Gly-Lys, were synthesized. The intensity of the umami and/or salty taste of these peptides and their Na salts was almost the same, despite their chemical structures being different. These results indicate that the acidic fragment as well as the basic fragment plays an important role in the taste production and intensity of delicious peptides, and that an umami or salty taste can be produced by the localization of the cation of the basic fragment and the anion of the acidic fragment. PMID- 7772835 TI - Nucleotide sequence of the FAD synthetase gene from Corynebacterium ammoniagenes and its expression in Escherichia coli. AB - The nucleotides of a bifunctional enzyme FAD synthetase gene, which showed both flavokinase and ATP:FMN adenylyltransferase activities, from Corynebacterium ammoniagenes were sequenced. The FAD synthetase gene product consisted of 338 amino acids and had a calculated molecular weight of 37,712. The deduced protein sequence of the FAD synthetase shared a homology with those of the protein X of Escherichia coli, which has been reported to have both flavokinase and ATP:FMN adenylyltransferase activities like the FAD synthetase of C. ammoniagenes, and the protein X of Pseudomonas fluorescens. From the analysis of the flanking sequences of the FAD synthetase gene, the gene organization and the operon structure around the FAD synthetase gene of C. ammoniagenes were thought to be different from those of Gram-negative bacteria. An over-expression system of the FAD synthetase of C. ammoniagenes was constructed in E. coli to study the structure and function of the protein. Under the tandem tryptophan promoter, the FAD synthetase activity increased 2231 times compared to that of non-transformed C. ammoniagenes. PMID- 7772836 TI - Isolation and structure of the Enterococcus faecalis sex pheromone, cOB1, that induces conjugal transfer of the hemolysin/bacteriocin plasmids, pOB1 and pYI1. AB - A bacterial sex pheromone, cOB1, which induces conjugal transfer of the Enterococcus faecalis hemolysin-bacteriocin (Hly/Bac) plasmid, pOB1, was isolated from the culture broth of pOB1-free E. faecalis. Its structure was found to be a hydrophobic octapeptide, H-Val-Ala-Val-Leu-Val-Leu-Gly-Ala-OH. The cOB1 peptide induced the mating response of not only pOB1 but also another incompatibility group Hly/Bac plasmid, pYI1. PMID- 7772837 TI - Taste evaluations of angiotensin I converting enzyme inhibitors, Leu-Lys-Tyr analogues. AB - Tastes of Leu-Lys-Tyr (LKY) analogues, a series of potent angiotensin I converting enzyme (ACE) inhibitory peptides were evaluated. Some of these analogues were found to be sweet, such as Val-Lys-Tyr and Ala-Orn-Tyr. Furthermore, the structural requirements for sweetness or decreasing the bitterness were investigated by considerations of the structure-taste relationship with LKY analogues. PMID- 7772838 TI - Ceruloplasmin concentration in human colostrum and mature milk. AB - The concentration of ceruloplasmin (CP) in human milk was obtained by measuring the increased absorbance of a solution containing apotransferrin and Fe2+ at 460 nm after adding the milk. The CP concentrations in colostrum and mature milk at less than 1 month after parturition were 4.45 +/- 1.23 mg and 4.09 mg +/- 1.47 mg/100 ml, respectively. In mature milk after more than one month, the CP concentration had decreased to 1.72 +/- 0.91 mg/100 ml. PMID- 7772839 TI - Conversion ratio of tryptophan to niacin in rats fed with a nicotinic acid-free, tryptophan-limiting diet. AB - The effects of amino acid composition on the conversion ratio of Trp to niacin in rats were investigated. The ratio in the group fed with a nicotinic acid-free, 9% casein-sucrose diet (basal diet) was 3.5%. This ratio was statistically decreased to 0.2% by the addition of 2% glycine, 0.078% L-threonine, and 0.2% L-cystine, and restored to 3.2% by the further addition of 0.1% tryptophan. From these results and our previous findings, it was considered that Trp imbalance might be a manifestation of niacin deficiency. PMID- 7772840 TI - A DNA region that complements on Escherichia coli cysG mutation in Thiobacillus ferrooxidans. AB - Thiobacillus ferrooxidans AP19-3 has a novel NADH-dependent sulfite reductase in the periplasmic space. The gene responsible for the appearance of NADH-dependent sulfite reductase activity was cloned into a vector plasmid pBR322 to give a 5.7 kb hybrid plasmid, pTHS1, which contains a 1.3-kb DNA fragment of T. ferrooxidans AP19-3. When pTHS1 was used to transform sulfite reductase deficient E. coli mutants, strain AT2455 (cysG), JM246 (cysI), and AT2427 (cysJ), it complemented only the E. coli cysG mutation. Since cysG codes for S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase, the enzyme involved in siroheme synthesis, the results indicate that the DNA region that codes for S-adenosyl-L methionine: uroporphyrinogen III methyltransferase is present in a T. ferrooxidans 1.3 kb DNA fragment on pTHS1. PMID- 7772841 TI - Effects of a peptide mixture with a high Fischer's ratio on serum and cerebral cortex amino acid levels and on cerebral cortex monoamine levels, compared with an amino acid mixture with a high Fischer's ratio. AB - Peptide mixtures with high and low Fischer's ratios (i.e., the ratio of branched chain amino acids to aromatic amino acids), obtained from an enzymatic hydrolysate of casein, and the corresponding amino acid mixtures were intragastrically force-fed to rats. Cerebral cortex monoamines were more influenced by the ingestion of the peptide than that of the amino acid mixture. PMID- 7772842 TI - Construction of a plasmid for high level expression of Escherichia coli phosphoenolpyruvate carboxylase. AB - The minimum size DNA fragment (3011 bp) containing the entire phosphoenolpyruvate carboxylase [EC 4.1.1.31] gene of E. coli was cloned into a modified plasmid vector of high copy-number. The gene expression was directed by its own promoter and the content of the enzyme reached about 30% of total soluble protein of the transformed cells. PMID- 7772843 TI - Antioxidative activity of hop bitter acids and their analogues. AB - Hop bitter acids, humulones (1) and lupulones (2), were shown to have potent DPPH radical scavenging activity (RSA) and lipid peroxidation inhibitory activity (LIA). Furthermore, 5-acetyl lupulones (3) and 4-methyl lupulones (4) had more potent LIA than native lupulones but no RSA. This result indicates that the beta, beta'-triketone moiety of the lupulones has LIA. PMID- 7772845 TI - Extraction of extracellular L-asparaginase from Candida utilis. AB - L-Asparaginase was extracted from Candida utilis cells using various reducing agents, 2-mercaptoethanol, dithiothreitol, or cysteine. The extraction of the enzyme depended upon the kind and concentration of reducing agents, temperature, time of incubation, and pH of buffer used. The enzyme was typically extracted by incubating the cells at 50 degrees C for 4 h in extraction solution containing 20 mM 2-mercaptoethanol in 20 mM potassium phosphate buffer (pH 7.0). The enzyme can be extracted from either cell precipitate or cell culture broth. The yeast cells were viable after extraction of L-asparaginase. PMID- 7772844 TI - Development of a protein-free medium with iron salts replacing transferrin for a human-human hybridoma. AB - Many protein-free media have been developed, because protein-free media are usually more economical than serum-free or serum-containing media and facilitate the purification of bioactive materials. We evaluated various iron salts and chelating agents replacing transferrin to develop a protein-free medium for a human-human hybridoma, HB4C5, and found out that ferric citrate was favorable for the production and the productivity of monoclonal antibodies. PMID- 7772846 TI - Application of direct current to protect bioreactor against contamination. AB - Bacteria cell suspensions were sterilized by direct electric current and the cell death rate was proportional to the current. When repeated hydrolysis of casein by immobilized mycelia was done under 0.06 A of direct electric current, contaminants were inhibited while the hydrolysis was stable for more than 10 batches (250 h). PMID- 7772847 TI - Two distinct species of corn cystatin in corn kernels. AB - Besides corn cystatin I (CC-I) we found, by cloning, another molecular species of cystatin, named corn cystatin II (CC-II), which was found by screening with CC-I cDNA as a probe. The dissimilarity in amino acid sequence between CC-I and CC-II was distinct around the N-terminal region. Enzymologically, CC-II protein expressed in Escherichia coli was a stronger inhibitor of cathepsin L than CC-I. PMID- 7772848 TI - Tissue- and development-specific expression of goat insulin-like growth factor-I (IGF-I) mRNAs. AB - We cloned four kinds of goat insulin-like growth factor-I (IGF-I) cDNAs. Each of them encodes the same mature IGF-I and different signal peptides. In this study, we analyzed expression of the four kinds of mRNAs in tissues in various developmental stages by a reverse transcriptase-polymerase chain reaction assay. The results suggest that their expression may be controlled by different promoters, the activities of which are tissue- and development-specific. PMID- 7772849 TI - pH-dependent inactivation and reactivation of recombinant sheep angiotensinogen. AB - Purified recombinant sheep angiotensinogen (rsAngn) lost 74% of the reactivity with human renin during storage at pH 8.0 and 4 degrees C. The inactivated rsAngn was reactivated by incubation at acidic pHs. This indicates that pH-dependent inactivation and reactivation occur in rsAngn. PMID- 7772850 TI - The Nurses and Midwives Pay Review Body. PMID- 7772851 TI - Patient assessment for day surgery. AB - Following medical selection of a patient for day surgery in either a hospital out patient clinic or general practitioner surgery, the patient requires assessment. This is usually achieved in one of two ways. The patient may be sent a postal questionnaire which is followed up on the telephone if a query occurs or he or she attends an assessment interview in the day surgery unit (D.S.U.) with a member of the nursing staff. From personal experience as a nurse teacher, patient assessment for day surgery is the one area of concern for theatre nurses if they are asked to work in the day surgery unit. This article is a brief overview of this area. Initially, assessment will be defined. Following this, patient assessment in the theatre setting will be compared with assessment of a patient about to undergo day surgery. To conclude, a summary of selected nursing competencies will be listed for successful day surgery patient assessment. PMID- 7772852 TI - Advances in anaesthesia. Some recent developments in techniques for short stay surgery. AB - Anaesthesia is now a world away from the single agent techniques of the 19th and early 20th centuries. There is an ever increasing requirement to obtain quicker throughput and minimal post-operative morbidity in every surgical specialty. Patients and managers expect a shorter and shorter hospital stay after surgery which would have required two or three times as long in hospital as little as ten years ago. Many, or perhaps most, of the advances in surgery since anaesthesia began in the 1840s have depended on advances in anaesthesia. The current trend to short stay surgery is no exception. I will give an historical perspective of the development of anaesthetic techniques which have permitted this development. I will describe some of the practical and theoretical considerations behind the techniques and a forecast of some of the techniques which are in development or might be anticipated in the future. PMID- 7772853 TI - The use of computer systems dedicated to day surgery. AB - As a management consulting firm and a system house which has developed computer systems specifically to support Day Surgery activities, we are often asked by nurses, doctors and managers of Day Surgery units to help clarify their needs for an information system. This article summarises the key questions which are asked, together with answers which we have given, based on our in-depth reviews at many hospitals which are reorganising and making significant investments in Day Surgery facilities. PMID- 7772854 TI - Re-using or mis-using? PMID- 7772855 TI - Safe disinfection of endoscopes. PMID- 7772856 TI - The mission statement formulated at the last meeting of the European Chief Nurses and WHO Collaborating Centres for Nursing and Midwifery. PMID- 7772857 TI - Day surgery: cheap option or challenge to care? AB - The tendency for surgery and associated nursing care to become short-stay is driven by so many considerations (of both dubious and desirable kinds) that it may be useful to attempt a little stock-taking on previous patterns of day operating and, by consulting a crystal ball, to consider possible implications for nursing and patient aftercare. PMID- 7772858 TI - Carbohydrate structures of a normal counterpart of the carcinoembryonic antigen produced by colon epithelial cells of normal adults. AB - Normal faecal antigen-2 (NFA-2) and non-specific cross-reacting antigen-2 (NCA 2), cross-reacting with anticarcinoembryonic antigen (CEA) antibodies, were found in normal human faeces and meconium, respectively. Because NFA-2, NCA-2 and CEA are considered as the same gene products, NFA-2 and NCA-2 should be normal counterparts of CEA produced by colon epithelial cells of normal adults and fetuses, respectively. Comparison of sugar chain structures of these three antigens is indispensable in order to unravel the structural alteration induced by malignant transformation and development of colon epithelial cells. The sugar chain structures of CEA (Yamashita, K. et al., Cancer Res., 47, 3451-3459, 1987) and NCA-2 (Yamashita, K. et al., J. Biol. Chem., 264, 17873-17881, 1989) were previously reported. In this paper, the structures of the oligosaccharides released from four NFA-2 samples by hydrazinolysis were studied by means of lectin-affinity column chromatography, endo- and exo-glycosidase digestion, methylation analysis, hydrazinolysis-nitrous acid deamination and electrospray ionization mass spectrometry. NFA-2 contains 24-27 mol of N-linked sugar chains/molecule, which is similar to NCA-2 (27 mol) and CEA (24-27 mol). In contrast to CEA, which contains approximately 8% high-mannose-type sugar chains, all sugar chains of NFA-2 are mono- to tetra-antennary complex-type chains having four types of tri-mannosyl cores, with or without bisecting N-acetylglucosamine and fucose residues. The structures of their outer chain moieties comprise Gal beta 1-->3(HSO(3-)-->6)GlcNAc, Neu5Ac alpha 2-->3Gal beta 1-->3GlcNAc, Type 1, repeating chain, Type 2, Type 2H, Type 1H, Lex, Lea and Leb antigenic determinants. Approximately 50% of the outer chain moieties of the oligosaccharides of NFA-2 contain Type 1 chain, in contrast to those of CEAs produced by the liver metastases of colon tumours in which only a trace amount of Type 1 chain was detected. PMID- 7772859 TI - The involvement of O-linked oligosaccharide chains of the sea urchin egg receptor for sperm in fertilization. AB - Recent investigations on the sea urchin egg receptor for sperm have led to its sequencing and the demonstration that it is a 350 kDa glycoprotein. In the current study, the N- and O-linked oligosaccharide chains were cleaved from the protein fractionated on concanavalin A-agarose. The putative O-linked oligosaccharide chains that did not bind to the lectin were further fractionated by anion-exchange chromatography. Using a competition bioassay that measured the ability of these oligosaccharide chains to inhibit fertilization, it was found that the N-linked chains were devoid of inhibitory activity. Rather, the inhibitory activity was localized to the O-linked chains, with the most highly charged, sulphated chains showing the highest inhibitory activity. The bioactive oligosaccharides were labelled by reduction and assayed for binding to sperm. The results of the binding assay, coupled with the fertilization bioassay, indicate that the oligosaccharides inhibit fertilization by binding to acrosome-reacted sperm. The bioactive oligosaccharide lacked species specificity in fertilization bioassays, unlike the intact receptor and a recombinant aglyco protein containing only the extracellular domain of the receptor. Since previous work showed that the recombinant protein inhibits fertilization species specifically and binds to acrosome-reacted sperm, a two-step model of sperm-egg interaction is proposed. The first step is postulated to be a low-affinity ionic interaction of the sulphated O-linked oligosaccharide chains of the receptor with sperm that is not species specific. This is followed by a high-affinity, species-specific interaction of the sperm with one or more binding sites on the polypeptide chain of the receptor. PMID- 7772860 TI - Structural definition of acylated phosphatidylinositol mannosides from Mycobacterium tuberculosis: definition of a common anchor for lipomannan and lipoarabinomannan. AB - Based on chemical analysis, we have previously concluded that the biologically important lipoarabinomannan (LAM) and lipomannan (LM) from Mycobacterium are multiglycosylated forms of the phosphatidylinositol mannosides (PIMs), the characteristic cell envelope mannophosphoinositides of mycobacteria. Using definitive analytical techniques, we have now re-examined the reported multiacylated nature of PIMs in order to gain a better insight into their possible roles as biosynthetic precursors of LM and LAM. High-sensitivity fast atom bombardment-mass spectrometry analyses of the perdeuteroacetyl and permethyl derivatives of PIMs from Mycobacterium tuberculosis and Mycobacterium leprae enabled us to define the exact fatty acyl compositions of the multiacylated, heterogeneous PIM families, notably the dimannoside (PIM2) and the hexamannoside (PIM6). Specifically, in conjunction with other chemical and gas chromatography mass spectrometry (GC-MS) analyses, the additional C16 fatty acyl substituent on PIM2 and its lyso form were defined as attached to the C6 position of mannose. We also present evidence for triacylated mannophosphoinositide as a common lipid anchor for both LM and LAM, and further postulate that acylation of PIM2 may constitute a key regulatory step in their biosynthesis. PMID- 7772861 TI - Genomic organization and expression of hamster UDP-N-acetylglucosamine:dolichyl phosphate N-acetylglucosaminyl phosphoryl transferase. AB - The hamster gene for uridine diphosphate N-acetyl-D-glucosamine:dolichyl phosphate N-acetylglucosaminyl phosphoryl transferase (L-G1PT) was found to extend over 6.5 kb and to contain nine exons. The exons ranged in size from 63 to 214 bp, encoding the 408 amino acid protein. The introns ranged from 85 bp to 1.4 kb. Upstream 5' sequences included two possible TATA boxes, one possible CCAAT box and at least two potential GC boxes. Heterologous expression was successful in Schizosaccharomyces pombe, and resulted in cells that were tunicamycin resistant and had 12-fold more L-G1PT activity than wild-type cells. Antiserum prepared to a hydrophilic peptide (residues 300-320) of the L-G1PT protein reacted with a 35-36 kDa protein in membrane samples from Chinese hamster ovary (CHO) cells and S. pombe cells that had increased levels of L-G1PT activity. In both cases, antigenic peptide competed with the 35-36 kDa protein detected by the antiserum. PMID- 7772862 TI - Primary structure of 12 neutral oligosaccharide-alditols released from the jelly coats of the anuran Xenopus laevis by reductive beta-elimination. AB - The O-linked oligosaccharides of the jelly coat surrounding the eggs of Xenopus laevis were analysed by 1H-NMR spectroscopy. Among the 12 neutral oligosaccharide alditols which have been characterized, three of them possess the following unusual structures: [sequence: see text] As previously observed for six other amphibian species, the carbohydrate chains of the jelly coat of Xenopus eggs display a high species specificity which could support a biological role during the fertilization processes. PMID- 7772864 TI - Purification and characterization of novel glycosidases from the bacterial genus Xanthomonas. AB - Enzymatic analysis of oligosaccharides using exoglycosidases has become a powerful tool for determining the sequence and structure of sugar chains. The principal limitation to these methods has been the lack of highly purified and well-characterized enzymes. Using fluorescently labelled carbohydrate substrates and TLC, we have developed a method to identify glycosidases with novel specificities. This screening method led to the discovery that bacteria of the genus Xanthomonas are a rich source of exoglycosidases. From Xanthomonas manihotis, eight novel exoglycosidases have been isolated and characterized. A novel beta-N-acetylglucosaminidase has been purified that, unlike those previously described, will cleave N-acetylglucosamine without cleaving N acetylgalactosamine residues. A novel beta-galactosidase has been isolated that preferentially hydrolyses beta(1-->3) galactosyl linkages. Three alpha mannosidases have been isolated that serve as useful reagents in the analysis of high-mannose oligosaccharide structures: alpha 1-3,6 mannosidase, alpha 1-6 mannosidase and alpha 1-2,3 mannosidase. An alpha 1-3,6 galactosidase has been purified that does not hydrolyse terminal alpha 1-4 galactose residues. Two fucosidases, alpha 1-3,4 fucosidase and alpha 1-2 fucosidase, are similar to enzymes purified from other sources. Together, these glycosidases provide powerful reagents for determining the sequence of complex carbohydrates. Equally important is their usefulness in selectively removing specific sugar residues and thereby creating novel carbohydrates for analysing the biological roles of oligosaccharides. PMID- 7772863 TI - Castanospermine analogues: their inhibition of glycoprotein processing alpha glucosidases from porcine kidney and B16F10 cells. AB - We have used a simple and efficient procedure for the synthesis of N-5 carboxypentyl-1-deoxynojirimycin, an affinity ligand for alpha-glucosidase I (Bernotas, R. C. and Ganem, B., Biochem. J., 270, 539-540, 1990). The affinity gel was used to purify alpha-glucosidase I in one step from crude extract. In subsequent steps, partially purified alpha-glucosidase II was obtained. We have synthesized several analogues of castanospermine and studied their inhibition of alpha-glucosidase I in vitro using purified alpha-glucosidase I and in vivo in cultured B16F10 cells. Although the castanospermine analogues were significantly less active against the purified enzyme (IC50 approximately 1-23 micrograms/ml) as compared to castanospermine (IC50 = 0.02 microgram/ml), several compounds had up to 30-fold higher activity than castanospermine against alpha-glucosidase I in B16F10 cells, based on the accumulation of G3M7-9N2 oligosaccharide-containing glycoproteins. These results suggest that these analogues with lipophilic side chains cross the membrane barrier more efficiently than castanospermine. Once inside the cell, they may be converted to their active metabolite, castanospermine, by cellular esterases to give enzyme inhibition. PMID- 7772865 TI - A beta-linked mannan inhibits adherence of Pseudomonas aeruginosa to human lung epithelial cells. AB - Adherence through carbohydrate-binding adhesins is an early step in colonization of the lung by gram-negative organisms, and because published data indicate that binding involves mannose groups, we tested the ability of a beta-linked acetyl mannan (acemannan) to inhibit adherence of Pseudomonas aeruginosa to cultures of human lung epithelial cells. Adherence of radiolabelled P.aeruginosa to A549 cells (a type II-like pneumocyte line) increased linearly with the duration of the incubation. Acemannan inhibited adherence of bacteria, and the extent of inhibition was related to the concentration of the mannan. Inhibition required continued contact between acemannan and the target epithelial cells; cells washed free of acemannan no longer discouraged bacterial binding. Comparison of binding between seven different strains of P.aeruginosa indicated that fewer mucoid than non-mucoid bacteria adhered, but binding of either phenotype was inhibited by acemannan. Mannose, methyl alpha-D-mannopyranoside, methyl beta-D-mannopyranoside and dextran did not affect adherence of any of the non-mucoid strains. Mannose inhibited adherence by one mucoid strain, but not the other, indicating differences between strains of the same phenotype. Since prior treatment of epithelial cells with concanavalin A did not affect acemannan-induced inhibition of bacterial adherence, we concluded that the inhibitory effect of acemannan probably does not involve mannose-containing receptors. PMID- 7772866 TI - Location of the active site of the bean alpha-amylase inhibitor and involvement of a Trp, Arg, Tyr triad. AB - Seeds of the common bean contain three homologous proteins: phytohaemagglutinin E, phytohaemagglutinin L and the lectin-like protein alpha-amylase inhibitor (alpha AI). Whereas the active site of lectins has been studied in great detail, there is no information on the active site of the related protein alpha AI, which exerts its biological activity by making a 1:1 complex with alpha-amylase. alpha amylase inhibitor is synthesized as a 30 kDa precursor glycoprotein that needs to be processed at Asn77 to form an active molecule. Comparison of the amino acid sequence of the bean alpha AI with that of the bacterial amylase inhibitor, tendamistat, suggested that a region around Trp188 might be involved in the inhibitory site. When a three-dimensional model of the bean alpha AI was constructed based on its homology to the legume lectins, this Trp region was alongside Asn77. To test this site hypothesis, mutants of alpha AI were created by site-directed mutagenesis of the cDNA and expressed in transgenic tobacco. The mutant proteins R74N and WSY188-190GNV, as well as the double mutant, were inactive as inhibitors. These findings suggest that the active site of alpha AI consists of W188, R74 and Y190, in analogy to the Trp-Arg-Tyr motif of tendamistat, and that the processing of the polypeptide at Asn77 may be necessary to bring these residues in close proximity. PMID- 7772867 TI - Genomic organization of human histo-blood group ABO genes. AB - We have isolated human genomic DNA clones encompassing 30 kbp of the histo-blood group ABO locus. The locations of the exons have been mapped and the nucleotide sequences of the exon-intron boundaries have been determined. The human ABO genes consist of at least seven exons, and the coding sequence in the seven coding exons spans over 18 kb of the genomic DNA. The exons range in size from 28 to 688 bp, with most of the coding sequence lying in exon 7. PMID- 7772868 TI - HL 60 leukaemia cells chemically induced to differentiate retain some surface glycan features of undifferentiated cells not found in normal leukocytes. AB - Human HL 60 myeloid leukaemia cells have the potential to differentiate into either macrophage-like cells or granulocyte-like cells under the stimulus of chemical treatments. Using glycotechnology procedures, the glycosylation patterns of differentiated and undifferentiated HL 60 cells were analysed and compared with those of normal human peripheral monocytes. Both in vitro differentiations result in significant morphologic and functional changes, but we observed that the glycosylation patterns of undifferentiated and differentiated HL 60 cells exhibit several common glycosidic features that are absent in normal peripheral monocytes: the presence of (i) bisecting beta-N-acetylglucosamine attached at the C-4 position of the beta-mannose of polyantennary complex-type carbohydrate chains and (ii) complex-type carbohydrate chains enriched with non-reducing terminal beta-N-acetylglucosamine residues. Moreover, the three populations of HL 60 cells express small amounts of biantennary complex-type structures (< 6%), whereas normal peripheral monocytes expressed > 20% of such structures. Thus, the cell glycosylation pattern could reflect the pathological state of the HL 60 cells. PMID- 7772869 TI - In situ accessibility of murine macrophage gangliosides. AB - Gangliosides are implicated in cell signal transduction. Prior to investigating this phenomenon in macrophages, the in situ accessibility of gangliosides to macromolecules was assessed for peritoneal macrophages isolated from normal C3H/HeN and endotoxin-hyporesponsive C3H/HeJ mice. C3H/HeJ resident and thioglycolate-elicited macrophage ganglioside patterns are the same as normal strains, and no strain differences in galactose oxidase accessibility for resident or thioglycolate-elicited macrophage gangliosides were found. The only gangliosides accessible to galactose oxidase in resident macrophages are GM1a structures. In thioglycolate-elicited macrophages, an additional ganglioside is accessible. For Escherichia coli-activated macrophages, where ganglioside distribution differs between strains, a difference in galactose oxidase accessible gangliosides also exists. Escherichia coli-activated C3H/HeN patterns show three triplets absent in C3H/HeJ patterns. There were no differences in ganglioside accessibility to Vibrio cholerae sialidase between the thioglycolate elicited C3H/HeJ and C3H/HeN macrophages. However, despite differences in sialidase-sensitive ganglioside content between E.coli-activated macrophages of these strains, sialidase accessibility for E.coli-activated macrophages was also similar. Sialidase-susceptible GM3 was cryptic in either strain under all conditions examined. The accessibility of murine macrophage gangliosides to galactose oxidase or sialidase was independent of their sialic acid species and chain length of the ceramide fatty acid. With the exception of GM3, major murine macrophage gangliosides are accessible in situ to macromolecules, especially to exogenous pathogenic bacterial sialidase which can alter macrophage cell surface characteristics. Altered macrophage ganglioside accessibility appears sometimes as a consequence, but not a cause, of C3H/HeJ endotoxin hyporesponsiveness. PMID- 7772870 TI - A new Dol-P-Man:protein O-D-mannosyltransferase activity from Saccharomyces cerevisiae. AB - The deletion of the protein mannosyltransferase 1 gene (PMT1) of Saccharomyces cerevisiae results in viable cells. O-Mannosylation of proteins is reduced to about half of the value in comparison to wild-type cells. In order to distinguish between the the PMT1 gene product (= Pmt1p) and residual transferase activity, an in vitro assay to measure Dol-P-Man:protein mannosyltransferase activity in cells deleted for PMT1 has been developed. The transferase activity of these cells exhibits a pH optimum of 6.5 as compared to pH 7.5 for Pmt1p. The Km value of the residual enzyme activity for the hexapeptide YNPTSV is 7 times higher than that of Pmt1p and shows a clear preference for the seryl residue. Differences in substrate affinities as well as in seryl/threonyl depend on the specific sequence of the peptides used in the enzyme assay. The new enzyme activity shows a significantly lower thermal stability as compared to Pmt1p. PMID- 7772871 TI - Preparation and structural characterization of large heparin-derived oligosaccharides. AB - Porcine mucosal heparin was partially depolymerized with heparin lyase I and then fractionated into low-molecular-weight (< 5000) and high-molecular-weight (> 5000) oligosaccharides by pressure filtration. The high-molecular-weight oligosaccharide mixture (approximately 50 wt% of the starting heparin) also contained intact heparin. This intact polymer complicates oligosaccharide purification. Thus, the low-molecular-weight fraction was used to prepare homogeneous oligosaccharides for structural characterization. The low-molecular weight oligosaccharide mixture was first fractionated by low-pressure gel permeation chromatography into size-uniform mixtures of disaccharides, tetrasaccharides, hexasaccharides, octasaccharides, decasaccharides, dodecasaccharides, tetradecasaccharides and higher oligosaccharides. Each size fractionated mixture was then purified on the basis of charge by repetitive semi preparative strong-anion-exchange high-performance liquid chromatography. This approach has led to the isolation of 14 homogeneous oligosaccharides from disaccharide to tetradecasaccharide. The purity of these heparin-derived oligosaccharides was determined by gradient polyacrylamide gel electrophoresis, analytical strong-anion-exchange high-performance liquid chromatography, capillary electrophoresis and one-dimensional nuclear resonance spectroscopy. The structure of these oligosaccharides was established using 600 MHz two-dimensional nuclear resonance spectroscopy. The spectral methods used included homonuclear correlation spectroscopy, nuclear Overhauser effect spectroscopy and heteronuclear multiple quantum coherence spectroscopy. The 1H/1H connectivities of the protons of each sugar residue in an oligosaccharide were established by two-dimensional homonuclear correlation spectroscopy, while 1H/13C assignments were made using 1H inverse detection. One- and two-dimensional nuclear resonance spectroscopic analysis of these heparin oligosaccharides showed two closely related groups of heparin-oligosaccharides are afforded by enzymatic depolymerization of heparin. One group is fully sulphated, having the structures delta UAp2S(1[-->4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S( 1]n-->4)-alpha- D GlcNpS6S, where delta UAp is 4-deoxy-alpha-L-threo-hex-4-eno-pyranosyluronic acid, GlcNp is 2-deoxy-2-aminoglucopyranose, IdoAp is idopyranosyluronic acid, S is sulphate and n = 0-6. The other group of oligosaccharides differ in that they contain beta-D-glucuronic acid in place of the alpha-L-iduronic acid residue nearest to the reducing end. The present study describes the isolation and structural elucidation of seven new oligosaccharides: an octasaccharide, two decasaccharides, two dodecasaccharides and two tetradecasaccharides. The utility of two-dimensional nuclear resonance spectroscopy to determine the structure of complex heparin oligosaccharides is also illustrated. PMID- 7772872 TI - A 23 kDa membrane glycoprotein bearing NeuNAc alpha 2-3Gal beta 1-3GalNAc O linked carbohydrate chains acts as a receptor for Streptococcus sanguis OMZ 9 on human buccal epithelial cells. AB - Streptococcus sanguis colonizes several human oral surfaces, including both hard and soft tissues. Large salivary mucin-like glycoproteins bearing sialic acid residues are known to bind various S.sanguis strains. However, the molecular basis for the adhesion of S.sanguis to human buccal epithelial cells (HBEC) has not been established. The present study shows that S.sanguis OMZ 9 binds to exfoliated HBEC in a sialic acid-sensitive manner. The desialylation of such cells invariably abolishes adhesion of S.sanguis OMZ 9 to the cell surface. A soluble glycopeptide bearing short sialylated O-linked carbohydrate chains behaves as a potent inhibitor of the attachment of S.sanguis OMZ 9 to exfoliated HBEC. The resialylation of desialylated HBEC with CMP-sialic acid and Gal beta 1,3GalNAc alpha 2,3-sialyltransferase specific for O-glycans restores the receptor function for S.sanguis OMZ 9, whereas a similar cell resialylation with the Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase specific for N-glycans is without effect. Finally, the same resialylation reaction carried out with CMP-9 fluoresceinyl-sialic acid as a substrate yields exfoliated HBEC bearing fluorescence on a single 23 kDa protein, when using the alpha 2,3 sialyltransferase as the catalyst. The latter finding demonstrates that this 23 kDa cell surface glycoprotein bears NeuNAc alpha 2-3Gal beta 1-3GalNAc O-linked sugar chains, a carbohydrate sequence which is recognized by S.sanguis OMZ 9 on exfoliated HBEC. In similar experiments carried out with a buccal carcinoma cell line termed SqCC/Y1, S.sanguis OMZ 9 did not attach in great numbers to such cultured cells, and these cells were shown to not express membrane glycoprotein bearing alpha 2,3-sialylated O-linked carbohydrate chains. PMID- 7772873 TI - Cardiomyoplasty: preservation of the latissimus dorsi muscle. AB - Muscle necrosis has been frequently observed in cardiomyoplasty patients and in experimental animal studies. The purpose of this study was to determine if heat shock could provide protection to skeletal muscle as has been shown in cardiac muscle. A 15-minute heat shock at 42 degrees C resulted in an immediate increase in HSP72 mRNA and was followed within 3 hours by a two-fold increase in HSP72. Surgical dissection of the latissimus dorsi muscle (LDM) followed by an ischemic period resulted in a two-fold increase in HSP72 in control LDM, whereas the already high levels in the heat-shocked LDM increased only slightly with surgery and ischemia. Citrate synthase activity and tissue histology indicated that heat shock did not protect the LDM from the imposed surgical trauma and ischemia insults used in this study. PMID- 7772874 TI - Renin, angiotensin II, and the development of effusions following bidirectional Glenn and Fontan procedures. AB - Pleural effusions are a troublesome complication following bidirectional Glenn and Fontan procedures. It was our hypothesis that effusions may be related to alterations in hormones that regulate fluid homeostasis. We made serial determinations (by radioimmunoassay) of antidiuretic hormone, cortisol, aldosterone, angiotensin II, and renin in patients undergoing bidirectional Glenn (n = 16) and Fontan procedures (n = 24). There were six patients who developed effusions following surgery. These patients had a different endocrinological pattern characterized by persistent elevation in renin (28 +/- 9 vs 9 +/- 5 ng/mL per hour, p < 0.01) and angiotensin II (110 +/- 33 vs 33 +/- 14 ng/L, p < 0.01) on the fifth postoperative day as compared to patients who did not develop effusions. These data demonstrate that patients who develop effusions following bidirectional Glenn and Fontan procedures have activation of their renin angiotensin system. PMID- 7772875 TI - Enhancement of ventricular mechanics following bidirectional superior cavopulmonary anastomosis in patients with single ventricle. AB - Seventeen consecutive patients undergoing bidirectional cavopulmonary anastomosis (BDCPA) using normothermic, noncardioplegic, cardiopulmonary bypass were studied preoperatively and early postoperatively (12.2 days) using transthoracic echocardiographic techniques. The purpose of the study was to assess the changes in left ventricular mechanics associated with the change in blood flow related to the BDCPA. Of the 17 patients, pulmonary atresia and tricuspid stenosis was present in 7, tricuspid atresia in 6, double inlet left ventricle in 3, and severe pulmonic stenosis with straddling of the tricuspid valve in 1. All other forms of single ventricle type anatomy and other patients undergoing BDCPA were excluded for the purposes of this study. The mean left ventricular end-diastolic volume index fell from 120 mL/m2 to 91.1 mL/m2 (p < 0.05). Similarly the left ventricular end-systolic volume index fell from 55.8 mL/m2 to 42.3 mL/m2, respectively (p < 0.05). The stroke volume index also fell from 64.5 mL/m2 to 48.8 mL/m2. Left ventricular ejection fraction was preserved and was unchanged in every patient. It was concluded that BDCPA, performed as described above, preserves left ventricular function and that the systolic and diastolic volumes as well as the stroke volume are significantly decreased as evidence of improvement of left ventricular mechanics. The continued use of the BDCPA either as a definitive procedure or as a staged procedure in preparation for total cavopulmonary connection is therefore endorsed. PMID- 7772876 TI - Pituitary adenomas complicating cardiac surgery: summary and review of 11 cases. AB - From the literature and our own experience, 11 cases of hemorrhage or infarction of a pituitary adenoma associated with cardiac surgery have been identified over a 13-year period. Males outnumbered females by 10 to 1. Symptoms observed were headache, lethargy, confusion, obtundation, unilateral ptosis, meiosis, and opthalmoplegia involving cranial nerves III, IV, and VI, visual field deficits, and hemiparesis. Diagnosis in most recent cases has been confirmed with computerized tomography or magnetic resonance imaging. All patients received adrenocortical steroid therapy initially. Eight patients underwent transsphenoidal hypophysectomy and all survived. One patient underwent decompression craniotomy and died. Intracranial surgery was deferred in 1 patient who survived and in another who died of a massive stroke. Residual neurological deficits were noted to be either absent, minimal, or resolving in 7 of the 9 patients who survived their initial hospitalization. While numerous mechanisms have been proposed to explain the hemorrhage and necrosis of a pituitary adenoma during heart surgery, no direct cause has been clearly identified. Surgical treatment is commonly necessary since untreated pituitary apoplexy is often fatal. Transsphenoidal hypophysectomy with decompression is the preferred method of treatment with a low perioperative mortality and fairly good long-term prognosis. PMID- 7772877 TI - Etiology and management of chronic valve disease in antiphospholipid antibody syndrome and systemic lupus erythematosus. AB - Unlike the Libman-Sacks vegetations of acute systemic lupus erythematosus (SLE), which are usually asymptomatic, valve involvement in chronic SLE and primary antiphospholipid antibody syndrome (APLAS) is similar to that of chronic rheumatic disease. Typical findings include valve thickening and nodularity, poor coaptation, and regurgitation. Elevated levels of antiphospholipid antibodies have been associated with the development of these valvular abnormalities in some but not all reported cases, and there are undoubtedly other etiologic cofactors. When cardiac valvular replacement is required, special attention must be given to preoperative reduction of elevated antibody levels, prevention of intraoperative thromboembolism, and prompt and aggressive postoperative anticoagulation. PMID- 7772878 TI - Coronary revascularization with the radial artery: new interest for an old conduit. AB - Between July 1992 and May 1994, 148 patients (18 females) underwent myocardial revascularization with a radial artery (RA) graft. The left RA was used in 97.3% of cases. All but two patients received at least one additional arterial conduit: 137 left and 59 right internal mammary arteries (IMA); 23 inferior epigastric arteries; and 21 right gastroepiploic arteries. Total arterial revascularization was achieved in 127 patients (85.8%). An average of 3.0 anastomoses/patient were constructed, 2.8 of which were arterial. RA proximal anastomoses were placed on the IMA in 75% of cases, while direct anastomosis to the aorta (23.7%) or to a saphenous vein (1.3%) was performed in the remainder. When anastomosed to an IMA, the RA was subsequently infused intraluminally with 10 mg of papaverine (1 mg/mL). The target artery was the left anterior descending or one of its branches in 14.7% of cases, the circumflex system in 76.3%, and the native right coronary or one of its branches in the remaining 9%. An infusion of diltiazem (4 mg/hour) was started once the aorta was unclamped, and patients were maintained on oral diltiazem for 6 months postoperatively. Operative mortality was 1.4% (2 patients), with the additional late deaths from noncardiac causes. In one patient there was a prolonged serous drainage from the RA donor site. Of the 144 survivors 140 are asymptomatic. Follow-up angiography demonstrated 100% early patency (< 30 days, 41 patients), and 94% late patency (6 to 20 months, mean 14 months, 30/32 patients). This study suggests the RA can be used safely as an alternative to saphenous vein in coronary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772879 TI - Thermal coronary angiography for intraoperative patency control of arterial and saphenous vein coronary artery bypass grafts: results in 370 patients. AB - BACKGROUND AND AIM OF THE STUDY: Early graft failure is often associated with technical failures and is therefore potentially avoidable. We used thermal coronary angiography (TCA) for intraoperative graft patency control in 370 patients undergoing routine coronary artery bypass graft surgery to determine whether consequent intraoperative bypass graft control may result in improved patency rates. METHODS: The temperature differences generated in between the myocardium and the grafts by injecting cold cardioplegic solution into the proximal end of a vein graft or by warmer blood running through an internal thoracic artery (ITA) graft were detected using three different infrared camera systems. The resulting "heat pictures" were evaluated for anastomotic patency and to outline graft anatomy. RESULTS: A total of 693 vein grafts were visualized. In 9.4% TCA failed to produce usable images. In the remaining 628 grafts, TCA revealed intraoperative patency in 98.8%. Out of 370 ITA grafts, only 14 could not be sufficiently visualized by TCA. Nineteen ITA occlusions (5.3%) were found: 5 intimal flaps; 11 suture imposed strictures; and 3 proximal ITA occlusions. All occluded grafts were subsequently revised or replaced. All sequential ITA as well as 15 right ITA grafts proved to have patent anastomoses. CONCLUSION: Using TCA an early graft dysfunction rate of 1% for vein grafts and 5.3% for ITA grafts could be demonstrated. Most occlusions were due to technical mistakes at the distal anastomosis. TCA outlines grafts and the attached coronaries by temperature differences without the need for a contrast agent. There is no interference with the surgical procedure. It is an ideal, noninvasive method to immediately document the success or failure of myocardial revascularization. PMID- 7772880 TI - Evaluation of St. Jude Medical mitral valve function by exercise Doppler echocardiography. AB - The aim of this study was to detect borderline mitral valve dysfunction in 100 asymptomatic patients with a St. Jude Medical valve. We studied rest and exercise hemodynamics by Doppler echocardiography. Study patients were divided into two groups according to the time since surgery: group A had valves implanted less than 5 years ago (44 patients), group B had valves implanted more than 5 years ago (56 patients). Although patients had no clinical signs of valve dysfunction, group B was found to have significant reduction of mitral valve area (p < 0.05). In the group A patients, mean gradients at rest increased from 4 +/- 2, 4 +/- 2, and 3 +/- 1 mmHg in valve sizes of 25, 27, and 29 mm, respectively, to 7 +/- 2, 7 +/- 3, and 5 +/- 2 mmHg with exercise. In the group B patients, mean gradients at rest increased from 7 +/- 1, 6 +/- 2, and 5 +/- 1 mmHg to 14 +/- 3, 13 +/- 3, and 10 +/- 4 mmHg, respectively, after exercise. The percent increase (mean) in peak pressure gradient with exercise was significantly higher in group B (more than 100%) than in group A (less than 80%) (p < 0.01). The percent increase in mean gradient with exercise was also significantly higher in group B (more than 100%) than in group A (less than 75%). In conclusion, patients with reduced valve area and more than a 100% increase of peak and mean gradients should be followed up carefully. If any signs or symptoms of heart failure develop, they must be considered as candidates for surgery. PMID- 7772881 TI - Management strategies for pulmonary vein thrombosis following single lung transplantation. AB - Pulmonary vein thrombosis following lung transplantation is an infrequently reported and often fatal vascular complication. Two cases of early pulmonary vein thrombosis following single lung transplantation are described. Both patients underwent surgical thrombectomy and anastomotic reconstruction following institution of cardiopulmonary bypass, but died of multiorgan failure within 5 days of diagnosis. The efficacy of transesophageal echocardiography as a diagnostic modality, as well as medical and surgical management strategies for thrombectomy, are discussed. PMID- 7772882 TI - Concomitant coronary artery bypass grafting and adrenalectomy for pheochromocytoma. AB - We report the first case of concomitant coronary artery bypass grafting (CABG) and adrenalectomy for pheochromocytoma. Which lesion to correct first and staging of the corrective procedures are highly controversial issues. Issues concerning pre- and intraoperative control of hemodynamic instability from catecholamine release are discussed. Preoperative alpha and beta blockade permitted excellent hemodynamic control in the operating room. Operative and postoperative courses were uneventful and the patient had complete resolution of his angina and hypertension. We conclude that concomitant CABG and adrenalectomy is the preferred approach when pheochromocytoma and symptomatic coronary artery atherosclerosis coexist. PMID- 7772883 TI - Mitral annuloplasty with a flexible linear reducer. AB - Although the ideal technique is still controversial, mitral valve reconstruction for mitral insufficiency usually includes an annuloplasty. From August 1985 to June 1993, 126 cases of pure, acquired mitral insufficiency were repaired by means of a posterior annuloplasty. Whatever the etiology, all types of mitral insufficiency allowing a mitral reconstruction were included. The annuloplasty, performed with a flexible linear reducer, was associated with valvular (62%) and subvalvular (11%) repairs. An associated surgical procedure was necessary in 62% of the patients. Operative mortality was 2.4%, and follow-up (mean 29 months) was complete for all survivors. Five-year survival was 90%. Five-year complication free rate for emboli was 91%. Only one patient at 12 months underwent reoperation to treat recurrent mitral insufficiency. Ninety-seven patients were in New York Heart Association Class I or II. Follow-up echocardiographic studies on 75% of eligible patients showed a free rate for significant regurgitation of 99%. Mean valve area was estimated at 2.88 +/- 0.85 cm2. These findings suggest that the flexible linear reducer seems to be a reliable device and a valid alternative for annuloplasty. PMID- 7772884 TI - [Molecular chaperones]. PMID- 7772885 TI - [Testing the knowledge of pupils and students about cancer and HIV/AIDS before and after the transmission of an educational message]. PMID- 7772887 TI - [The surveillance of streptococcal infections at the level of the National Reference Center for Streptococcus in 1987-1993]. PMID- 7772886 TI - [A prevalence study of serum markers in hepatitis virus infection in the epidemiological anamnesis of the population]. AB - Pandemic of the infections with hepatitis viruses is a priority in public health. In Romania, the very high acute and chronic morbidity by viral hepatitis demands the rapid implementation of a feasible preventive program. In the population of 5 districts from Transylvania we conducted a sero-epidemiological survey in order to find the real and specific characteristics of the prevalence of the infections with hepatitis viruses. The study was a cross-sectional study on the anamnestic presence of the infections in the population. The evolution of the cumulative prevalence of infections with HAV (74.3%) and HBV (31.7%) are proving a high endemoepidemicity. For the infections with HCV (4.9%) and HDV (1.7%) we observed an active process of endemicity. The high rate of persistent infections following HBV acute infections (19.1%) suggests a growing-up tendency of chronic hepatic diseases. In actual epidemiologic conditions, the rate of exposure to a potential hepatic viral infections in the population we studied could be 1.68 infections/person, during a period equal to life expectancy at birth. PMID- 7772889 TI - [Nosocomial infections: past, present and future]. PMID- 7772888 TI - [A comparison of an immunoenzyme reaction (Platelia R) with a complement fixation reaction for detecting antibodies against M. pneumoniae]. PMID- 7772890 TI - [Susceptibility to nosocomial infections]. PMID- 7772891 TI - [The estimation of the risk of nosocomial infections in maternity hospitals]. PMID- 7772892 TI - [The epidemiological approach to health problems]. PMID- 7772894 TI - [A prevalence study of viral hepatitis B infection in a closed-type children's collective--the Cluj-Napoca Children's Orphanage]. PMID- 7772893 TI - [Epidemiological observations on the evolution of influenza in the city of Iasi in the epidemic season of 1993-1994]. AB - The epidemiological, clinical and laboratory data of influenza and other respiratory diseases recorded during the epidemic season 1993-1994, as they resulted from the comparative analysis of the cases reported weekly and those recorded through the "sentinel" collectivities method, are presented. The findings at admissions to the Infectious Diseases Hospital, Military Hospital, Diagnosis and Treatment Centre for Pupils and Students and the solicitation for medical care at the Emergency Ambulance Service were also interpreted. The involvement of A/Beijing/32/92/(H3N2) influenza virus was confirmed by evidencing the seroconversion on two serum samples tested through RIH, while for others antigens anamnestic reactions were recorded. The influenza epidemic had affected all age groups, with horizontal extension, a first rise in December 1993 followed by the decline determined by winter vacation being notice. A second epidemic rise, much stronger, started beginning with the last month of January and reached a peak at mid February, followed by a marked decline. PMID- 7772895 TI - [Preliminary considerations in a semiquantitative microbiological study in catheter-related infection]. AB - In the interval September 1993-April 1994, 38 catheters from children admitted to the Children's Hospital of Iasi were examined microscopically and by semiquantitative culture, in the children with sepsis and/or positive catheters hemocultures being performed concurrently. Twenty eight of these catheters proved to be sterile, the other 10 being positive to coagulase-negative staphylococci, gram-negative bacilli from Klebsiella-Enterobacter group, Candida species, the number of colonies/plate varying generally in concordance with the microscopic positive score. Of the 6 cases with > 50 colonies/plate, 3 progressed to septicemia, their hemocultures being positive to the same bacterial species demonstrating an identical sensitivity spectrum to antibiotics (2 cases with Enterobacter cloacae, 1 case with Klebsiella oxytoca). These results correlated with a bacterioscopic score > +1, in a case, which concomitantly presented local phenomena of phlebitis, a PNC score +3 being recorded. To conclude with, the results of microscopic examinations and semiquantitative culture can differentiate the contaminated catheters from those at bacteremic risk. For defining the cutoff level of the significant number of colonies/plate, more positive samples are needed. PMID- 7772896 TI - [The infectious process. The pathogenicity factors of bacteria]. PMID- 7772897 TI - Liposarcoma of the mesocolon--case report of a rare lesion. AB - A middle-aged man with a 2-month history of lower abdominal pain was found to have a large left-sided abdominal lump. Radiological investigations (barium enema, ultrasound, and computed tomography scan) revealed a mass lesion in the area of the descending colon, the sigmoid colon, and the rectum. Flexible sigmoidoscopy showed only mucosal edema and luminal narrowing. At laparotomy, a diffuse thickening of both the descending and sigmoid mesocolon extending into the mesorectum was seen, which suggested an inflammatory pathology. A left hemicolectomy with Hartmann's procedure was performed. After obtaining a histopathological diagnosis of liposarcoma of the mesocolon, an abdominoperineal resection of the rectum was done. The patient was advised to undergo postoperative radiotherapy but he did not comply and was thereafter lost to follow-up. PMID- 7772898 TI - Nonanastomotic aneurysm formation in a Dacron arterial graft: report of a case. AB - Dacron prostheses are the most widely used grafts in replacement procedures for abdominal aortic aneurysms, having been proven as the most reliable substitute for arterial replacement. However, we present herein the rare case of an 82-year old woman in whom nonanastomotic aneurysm formation occurred in the graft as a complication associated with a Dacron prosthesis. The patient presented with a pulsatile mass in the right inguinal region. She had undergone surgery 13 years earlier for an abdominal aortic aneurysm, at which time an aortobifemoral graft reconstruction had been performed with a double-velour knitted Dacron prosthesis. The pulsatile mass was found to be a nonanastomotic aneurysm of the right limb of the bifurcated graft with an intact distal anastomosis. In this case, the development of the graft aneurysm seemed to result from deterioration of the Dacron prosthesis itself due to mechanical fatigue caused by the inguinal band. PMID- 7772899 TI - A small pedunculated adenomatous polyp of the colon found to contain the focus of invasive carcinoma extending to the serosa: report of a case. AB - A small pedunculated polyp was detected among other polyps in the transverse colon of a 64-year-old man, the resected specimen of which showed an adenomatous polyp 1 cm in diameter, containing the foci of adenocarcinoma invading the submucosa, muscularis, and serosa. This case report stresses the importance of performing careful pathologic examination of resected specimens obtained from endoscopic polypectomy, even for small pedunculated colon polyps. PMID- 7772900 TI - Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: report of a case. AB - A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the "sandwich method," and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed. PMID- 7772901 TI - Successful surgical treatment of a pseudoaneurysm after composite graft replacement of the aortic valve and ascending aorta: report of two cases. AB - Composite graft replacement of the ascending aorta and aortic valve has now become a safe surgical procedure; however, early and late complications still frequently occur. Anastomotic dehiscence after a composite graft replacement is one potentially lethal complication. We herein report two cases of a pseudoaneurysm caused by dehiscence of the right coronary anastomosis, and the proximal aortic anastomosis. A follow-up with an echocardiogram and computed tomography scan was found to be very useful and accurate. We thus successfully treated two cases of pseudoaneurysm using either Bentall's or Carbrol's procedures. PMID- 7772902 TI - Advanced primary non-Hodgkin's lymphoma of the small intestine in childhood: report of four cases. AB - Primary non-Hodgkin's lymphoma of the small intestine (PLI) is an uncommon malignancy in childhood which carries a poor prognosis. Consideration of the possible diagnosis of PLI is important when children have vague abdominal symptoms, since thoughtful multidisciplinary treatment can result in a better prognosis. This paper reports the cases of four children who have presented to our hospital since 1985 with advanced stage III or IV PLI. All the children had a huge abdominal mass but none of them had complete intestinal obstruction. Regarding the diagnosis, ultrasonography frequently reveals a hypoechoic thickening of the intestinal wall with dilated intestinal loops. A delayed primary or second-look operation may be the treatment of choice following adequate chemotherapy, while total parenteral nutritional support may prevent gastrointestinal complications. Three of the four patients have been in complete remission for 2 to 4 1/2 years since their initial treatment. PMID- 7772903 TI - The effect of intraportal PGE1 on warm ischemic liver damage. AB - To determine the most effective route of administering prostaglandin E1 (PGE1) to inhibit warm ischemic liver damage, 90-min warm ischemia was established in a canine model. The dogs were divided into three groups according to the treatment given. Thus, group A (n = 10) was the control group which received no treatment, group B (n = 7) was administered PGE1 intravenously, and group C (n = 7) was administered PGE1 intraportally. PGE1 was continuously administered before and after the ischemia at a rate of 0.02 microgram/kg/min. The branched-chain amino acid to aromatic amino acid ratio in the hepatic vein, and the arterial ketone body ratio of acetoacetic acid to beta-hydroxybutyric acid, were examined to observe the metabolism of each amino acid and the oxidation-reduction ability of hepatocytes. Both ratios were maintained only in the group C dogs, three of which survived for over 3 days, whereas in groups A and B, all the dogs died within 24 h. The results of this study imply that the intraportal administration of PGE1 was more effective against warm ischemic liver damage than the intravenous administration of PGE1. PMID- 7772904 TI - Direct hemoperfusion under infrahepatic inferior vena caval isolation for the intraarterial chemotherapy of pelvic tumors. AB - A new simple technique consisting of direct hemoperfusion under infrahepatic inferior vena caval isolation for intraarterial chemotherapy of pelvic tumors is herein described. The inferior vena cava is occluded at the infrahepatic level by means of balloon inflation using a balloon-tipped catheter (16F), which is placed through the right greater saphenous vein. The isolated infrahepatic vena caval blood is withdrawn by a centrifugal pump through a catheter (16F) in the contralateral greater saphenous vein and is filtered by direct hemoperfusion during intraarterial infusion of anticancer drugs. Venous reentry is provided by the central lumen of the balloon-tipped catheter. This procedure was used sequentially on two different occasions to treat a patient with an extensive pelvic tumor. Good hemodynamic stability and a reduction of the systemic drug toxicities were confirmed in both trials. Therefore, we believe that this technique is technically feasible and highly effective in reducing systemic toxicities during high-dose intraarterial chemotherapy for pelvic tumors. PMID- 7772905 TI - Classical and endovascular surgery: indications and outcomes. AB - For more than 40 years, endarterectomy and bypass grafting have been the primary means of surgically revascularizing peripheral vessels threatened by atherosclerotic disease. However, with today's endovascular technology, stenoses and occlusions in nearly every circulatory system can be approached intraluminally with a wide variety of techniques: thrombolysis, laser angioplasty, atherectomy, balloon dilation, and intravascular stents. Just as exciting is the newer technique of endoluminal grafting, which has extended percutaneous therapy to aneurysmal disease in the thoracic and abdominal aorta and distal arteries, as well as to long-segment occlusive disease. Today's vascular surgeon is in a unique position to combine his or her classical surgical training with these catheter-based interventions. Certainly, the potential advantages of percutaneous therapy as compared to surgical reconstruction are significant: no general anesthesia or lengthy incisions, shorter hospitalization, lower morbidity and mortality, earlier intervention in the course of the disease, and less complicated reapplication in the event of disease recurrence. Undoubtedly, endovascular techniques will become a major component of the vascular surgeon's armamentarium, and as we approach the year 2000, they will be the treatment of choice in nearly every vascular pathology and circulatory system. PMID- 7772906 TI - Lymphangitis carcinomatosis of the lesser omentum: a prognostic factor in gastric cancer. AB - A series of 126 patients with gastric cancer who underwent radical gastrectomy with systemic lymph node dissection revealed 9 patients who survived for a median time of only 3 months. Of these 9 patients, 4 were classified by the UICC system as stage II and 5 as stage III, all of whom had lymphangitis carcinomatosis of the lesser omentum. These data suggest that although lymphangitis carcinomatosis of the lesser omentum is an uncommon finding, if it is present, curative surgery is impossible and an operation should therefore be limited to tumor palliation. PMID- 7772907 TI - The effects of using a leukocyte removal filter during cold blood cardioplegia. AB - During myocardial ischemia, neutrophils and platelets exert negative effects on the myocardium. In this study, we used a leukocyte removal filter during cardioplegia, and investigated its effect on myocardial damage during reperfusion by measuring the plasma levels of granulocyte components, platelet components, and cardiac enzymes [creatinine phosphokinase (CK) and creatinine phosphokinase myocardial band (CK-MB)] in 24 patients who underwent cardiopulmonary bypass. The patients were divided into two groups of 12 according to whether or not a filter was placed in the cardioplegic route. Blood samples were drawn directly from the coronary sinus before aortic cross clamping, and at 1, 5, and 15 min after declamping. Group F, which had the filter, showed better cardiac enzyme and lipid peroxidation results than group N, which did not. The results of this study suggest that the application of a filter during cold blood cardioplegia may reduce myocardial damage. PMID- 7772908 TI - Intravenous digital subtraction angiography for the evaluation of renal artery blood flow following the removal of a neuroblastoma. AB - There have been several reports of acute renal failure following the resection of an abdominal neuroblastoma combined with ipsilateral nephrectomy as well as the atrophy or disappearance of an unresected kidney after tumor resection. Spasms or thrombosis of the renal artery during tumor excision are considered to be the major cause. Since 1989, intravenous digital subtraction angiography (IVDSA) has been used to evaluate the renal artery blood flow immediately following surgery in seven patients with abdominal neuroblastomas. IVDSA was performed using a central venous catheter inserted prior to surgery. In all seven patients, IVDSA provided clear images for the evaluation of renal artery blood flow. In one of the two patients whose kidneys briefly became cyanosed during tumor excision, IVDSA demonstrated an occlusion of the renal artery and prompt measures could be taken to reestablish the blood flow. No complications of IVDSA occurred in any of the seven patients. IVDSA using a central venous catheter was thus considered to be useful for evaluating the renal artery blood flow in patients with a suspected renal artery blood flow disturbance without any risk of complications, and this modality obviated the need for intraarterial angiography. PMID- 7772909 TI - One hundred and one cases of bronchoplasty for primary lung cancer. AB - The results of 101 consecutive bronchoplasties performed between 1979 and 1993, including 8 cases of pneumonectomy, 88 cases of lobectomy, 3 cases of segmentectomy, and 2 cases of bronchial resection, are herein reported. Squamous cell carcinoma was the most common disease (59%) followed by adenocarcinoma (30%) and other diseases (11%). Anastomosis was satisfactory in 96 cases. Among the five stenosed cases, local recurrence was found in two cases, and there were three benign strictures. Two of the three benign strictures were treated with bouginage. The pulmonary artery was concomitantly reconstructed in seven cases with satisfactory results. Preoperative chemoradiotherapy was performed in 15 advanced cases and was followed by acceptable surgical results. The 5-year survival rate, according to the postoperative staging of the 86 patients without induction therapy, was 86% in stage I (19 patients), 49% in stage II (21 patients), and 27% in stage IIIA (40 patients). The overall survival rate was 46% at 5 years. There were two indications for this procedure i.e., a positive resection margin in 59 cases and positive hilar nodes in 42 cases. Better survival was noted in patients with squamous cell carcinoma, stage I, and surgery was thus selected for a positive resection margin, and not for a positive node. PMID- 7772910 TI - Glucagon responses in rabbits with obstructive jaundice and a low energy status in the liver. AB - Glucagon has a choleretic effect and also stimulates energy-consuming reactions, such as gluconeogenesis and ureogenesis in the liver. The effect of glucagon on energy metabolism in the liver was analyzed in rabbits with obstructive jaundice that had severe liver damage, indicated by significantly lower hepatic energy charge levels. The gluconeogenetic responses to glucagon administration, as shown by increases in the plasma glucose levels, were usually observed in normal rabbits, but these responses were completely depressed after glucagon administration in rabbits with obstructive jaundice. The energy charge levels in the latter animals decreased even further after glucagon administration. Even though the energy consumption for gluconeogenesis after glucagon administration was limited in the jaundiced rabbits, it was sufficient to cause a deterioration in the hepatic energy balance. The above findings show that the administration of glucagon increases the amount of energy expended in the liver following a reduction in the hepatic energy charge in rabbits with obstructive jaundice. Therefore, even though glucagon has a choleretic effect, it should be administered carefully to patients with obstructive jaundice, especially in those with severe liver damage, such as in patients with cholangitis. PMID- 7772911 TI - The effect of prolonged hyperglycemia on metabolic alterations in the subtotally pancreatectomized rat. AB - A delayed onset of diabetes is characteristic of subtotally pancreatectomized patients in whom persistent hyperglycemia per se is documented to lead to the development of insulin resistance. This study was conducted to elucidate the metabolic alterations seen during transition of the acute to chronic phase after subtotal pancreatectomy (SP). Eight male Sprague-Dawley rats were studied 2 weeks after surgery in the acute phase, and the other eight at 4 weeks in the chronic phase. Phosphoenolpyruvate carboxykinase (PEPck) for gluconeogenesis and the malic enzyme for de novo fatty acid synthesis in the liver showed a reciprocal change, the former activity being increased, while the latter was suppressed. Both alterations were more pronounced in the chronic phase. In the acute phase, lipoprotein lipase (LPL) for triglyceride clearance decreased in the adipose tissue, while that in the cardiac and skeletal muscle became significantly elevated. The latter elevations were decreased in the chronic phase. Sustained hyperglycemia in the SP rats not only increased the changes in PEPck and malic enzyme activities but reversed the tissue-specific muscle LPL elevations. These changes might help to explain the wasting condition seen in surgically induced diabetic patients. PMID- 7772912 TI - The preoperative nutritional assessment of surgical patients with hepatic dysfunction. AB - The precise influence of malnutrition on postoperative complications in patients with hepatic dysfunction is not well known. In phase I of the present study, we evaluated the nutritional status of 102 patients with hepatic dysfunction who were admitted for elective hepatobiliary or pancreatic surgery, and a model for the prediction of postoperative complications was developed using a computer based stepwise regression procedure. The equation for this Prognostic Nutritional Index for Surgery (PNIS) was calculated by [-0.147 x (% weight change) + 0.046 x (% ideal body weight) + 0.010 x (actual triceps skinfold thickness as a % of standard value) + 0.051 x (hepaplastintest)]. In phase II this model was prospectively tested in 182 patients, including 145 with hepatic dysfunction. A total of 18 patients were classified as having a poor prognosis (PNIS < 5) and all of these patients in fact developed postoperative complications: 128 patients were classified as having an intermediate prognosis (5 < or = PNIS < 10), 23 (18.0%) of whom developed postoperative complications, and none of the 36 patients who were classified as having a good prognosis (PNIS > or = 10) developed any postoperative complications. These results demonstrate the importance of performing a thorough preoperative nutritional assessment of patients with hepatic dysfunction as malnourished patients with PNIS < 10 may need preoperative nutritional management, even when their surgical procedures are not major. PMID- 7772913 TI - Emergency management of caustic ingestion in adults. AB - A study of 57 patients admitted to the Department of Emergency Surgery at the Ospedale Maggiore in Milan between 1980 and 1992 following the recent ingestion of a caustic substance is presented herein. Through this study, an aggressive diagnostic and therapeutic approach has been employed, including early surgery which plays a fundamental role in the prevention of acute hemorrhagic or perforative complications as well as in the development of scar tissue and neoplastic strictures over time. The criteria for early emergency surgery were the presence of endoscopic grade 3 and 4 lesions as well as those on the borderline between grades 2 and 3 with clinical symptoms. In 11 patients with lesions of moderate severity, the treatment of choice was medical therapy, which required subsequent surgical intervention for strictures in 5 patients. In 13 patients with severe lesions, an early surgical approach was performed with a mortality rate of 23%. PMID- 7772914 TI - Lymph node metastasis and the recurrence of esophageal carcinoma with emphasis on lymphadenectomy in the neck and superior mediastinum. AB - A series of 335 patients with squamous cell carcinoma of the thoracic esophagus undergoing resection and reconstruction via a right thoracotomy and laparotomy with cervical anastomosis between 1973 and 1990, were reviewed. Prior to 1982, the removal of lymph nodes was limited to the nodes in the mediastinum below the tracheal bifurcation and upper abdomen (142 patients). Nodal metastases were found in 89 of these patients at operation. The upper abdominal nodes were the most frequent sites of metastasis (47.2%). None of the 38 patients with positive nodes sampled from the neck and superior mediastinum survived for more than 45 months. In the 50 patients with recurrences, 30 were in the neck and/or superior mediastinum. During or after 1983, the superior mediastinal nodes, particularly the bilateral recurrent nerve nodal chains, were routinely removed (193 patients). Nodal metastasis was proven in 131 of the 193 patients, in whom 87 (45.1%) had metastasis in the neck and superior mediastinum. Eleven of these 87 patients survived for 45 months or more. In the 61 patients with recurrences, 20 were in the neck and/or superior mediastinum. These data suggest that recurrent nerve nodal chains should be removed to improve survival in patients with esophageal carcinoma. PMID- 7772915 TI - Concomitant coronary bypass grafting and curative surgery for cancer. AB - The surgical management of patients with concomitant critical coronary artery disease (CAD) and surgically resectable cancer is controversial. We evaluated 19 patients who underwent concomitant coronary artery bypass grafting (CABG) and curative operation for cancer of the stomach in 9 patients, the colon in 4, the lung in 4, and the breast in 2. Each cancer operation was performed under stable hemodynamics without any serious bleeding tendency, immediately after CABG with an average of 2.5 +/- 0.8 grafts. There were no operative deaths and no incidences of perioperative myocardial infarction. Postoperative complications developed in three of the patients with lung cancer: respiratory dysfunction caused by phrenic nerve paralysis in two and mediastinitis in one. During the mean follow-up period of 33 +/- 23 months, 5 patients died of recurrent cancer or non-cardiac disease; however, all 19 patients remained free from any postoperative cardiac events and their quality of life apparently improved. This experience suggests that such simultaneous correction would be safe and beneficial in carefully selected patients who have surgically correctable CAD and potentially curable cancer. PMID- 7772916 TI - Effects of left intraatrial infusion of prostaglandin E1 after open-heart surgery. AB - The hemodynamic effects of a left intraatrial infusion of prostaglandin E1 (PGE1) given to ten patients after open-heart surgery (LA group), were compared with those following no treatment in a control group of ten patients, and to those following a right intraatrial infusion given to another ten patients (RA group). PGE1 was infused at a rate of 0.03 microgram/kg/min in the RA group and at 0.003 microgram/kg/min in the LA group, and hemodynamics were measured immediately after surgery, then 3, 6, and 12 h after the PGE1 infusion was commenced. The heart rate, right atrial pressure, left atrial pressure, and mean pulmonary arterial pressure remained almost unchanged in all three groups; however, the mean radial arterial pressure and systemic vascular resistance index decreased, and the cardiac index increased in the RA and LA groups. The pulmonary vascular resistance index decreased only in the LA group. Thus, a much smaller dose of PGE1, being one-tenth of that used for the right atrial infusion, administered directly into the left atrium yielded almost the same hemodynamic effects as the larger dose infused into the right atrium. Furthermore, this method of infusing PGE1 is safe, efficacious, and cost-efficient. PMID- 7772917 TI - Identification and biochemical characterization of human plasma neutrophil inhibitor in vitro. AB - In this study, assessment by a flow cytometric method using dichlorhydroxy fluorescin diacetate (DCFADH) in vitro revealed that human peripheral blood inhibits the production of active oxygen species by human peripheral neutrophils. It was also revealed that among the blood components, the plasma fraction inhibits active oxygen production most strongly. This plasma inhibitory activity was dose-dependent. Human serum also exerted an inhibitory activity; however, its activity was only one-third that of plasma. Moreover, when HL-60 human promyelocytic leukemic cells, with or without differentiation into the neutrophils by culturing with dimethyl sulfoxide (DMSO), active oxygen, which was also inhibited by plasma, was produced. Heat inactivation of the plasma did not alter the inhibitory activity, and gel filtration analysis showed that the peak activity was associated with a molecular mass of 70,000. The results of this study indicate that human plasma contains one or more substances that inhibit the active oxygen production of neutrophils, which may play an important role in inhibiting unneeded neutrophil activation in the bloodstream. PMID- 7772918 TI - Malignant lymphoma of the thyroid with evidence of an Epstein-Barr viral infection concomitant with thalassemia minor: report of a case. AB - We report herein the unusual case of a 53-year-old Japanese man in whom malignant lymphoma of the thyroid was found to coexist with asymptomatic thalassemia minor and an elevated titer (1:80) of immunoglobulin G against the Epstein-Barr viral capsid antigen. A total thyroidectomy with lymphadenectomy was performed, and the thyroid was found to be almost replaced by the neoplasm, the microscopy of which revealed malignant lymphoma of the diffuse, large-cell type. The existence of this case led us to question whether malignant lymphoma of the thyroid and an elevated titer for the Epstein-Barr virus might have a possible mutual association. PMID- 7772919 TI - The safe and complete removal of a carotid body tumor with elements suggestive of a malignant potential by employing an intraluminal shunt: report of a case. AB - The carotid body tumor is a relatively rare neoplasm arising from the intercarotid paraganglions. We report herein the case of a patient with a Shamblin group 2 type carotid body tumor for which safe and successful removal was facilitated by the insertion of an intraluminal shunt. The patient was a 54 year-old man who presented with a spherical elastic mass, 4.8 x 3.7 cm in size, on the right anterior aspect of his neck, which was diagnosed as a carotid body tumor by diagnostic imaging. Because the tumor was suspected to be malignant based on the operative findings, which included invasive adhesion to the carotid artery, an intraluminal shunt was inserted, allowing for safe and complete removal. Histologically, this tumor showed malignant potential with sporadic mitoses and incomplete capsular invasion. Thus, it is recommended that an intraluminal shunt be employed for the removal of a carotid body tumor when it is found to be tightly adherent to the carotid artery during the operation. PMID- 7772920 TI - Complete endobronchial obstruction and left non-aerated hemithorax caused by a leiomyoma: report of a case. AB - Presented herein is the case of a 27-year-old man in whom an endobronchial tumor was found causing complete obstruction of the left main bronchus. The tumor was successfully removed by performing sleeve resection of the left main bronchus without pulmonary resection, immediately following which the left lung became reinflated. Subsequent histological study of the resected tumor confirmed that it was a leiomyoma, a type of benign tumor that is rarely found in the lung. PMID- 7772921 TI - Thrombosed tricuspid valves presenting some 20 years after the surgical correction of Ebstein's anomaly: report of two cases. AB - We present herein the cases of two patients who were diagnosed as having thrombosed tricuspid valves by electrocardiography after undergoing valve replacement with Starr-Edwards caged ball valves for Ebstein's anomaly 19 and 27 years earlier. In both patients, the valves were found to be attached to the right ventricular septum and covered with massive thrombus, the balls being completely jammed in a half-open position in the cages. Re-replacement of the valves was successfully performed with Hancock II porcine heterograft prostheses and both patients are now classified as being in Functional Class I or II. PMID- 7772922 TI - Recurrent splenic artery aneurysms developing after aneurysmectomy without splenectomy: report of a case. AB - We report herein the case of a 47-year-old man who developed a huge splenic artery aneurysm (SAA) with splenomegaly, for which ligation of the splenic artery and partial aneurysmectomy was performed. A celiac arteriogram taken 2 months postoperatively revealed that two small aneurysms had developed in the collateral vessels, indicating that increased blood flow through the collateral circulation could be responsible for the formation of secondary aneurysms. This postoperative change suggests that the etiology is related to the SAA and thus, the possibility that aneurysms may develop in the collateral vessels following spleen-preserving procedures for SAA must be borne in mind and careful follow-up performed at regular intervals. PMID- 7772923 TI - Familial nesidioblastosis in two sisters. AB - We herein present two female siblings with persistent hyperinsulinemic hypoglycemia in the neonatal period who were diagnosed as having familial nesidioblastosis. Despite both the administration of diazoxide and the intravenous infusion of glucose, one of the affected infants died of severe metabolic acidosis at about 1 month of age, before pancreatectomy could be performed. The other, in whom the disorder was diagnosed early, also failed to respond to conservative medical treatment and ultimately required a 99% pancreatectomy for control of hypoglycemia. A third female sibling was normal. The possibility of familial nesidioblastosis should thus be considered in the case of neonatal intractable hypoglycemia to ensure a prompt diagnosis and allow for early surgical intervention when indicated. The relevant literature on this life-threatening disorder is also reviewed. PMID- 7772924 TI - The endoscopic removal of a foreign body in the pericardial cavity following cardiac surgery. AB - We were able to successfully remove a needle and suture through a pericardial drain following cardiac surgery by means of a simple method using a bronchofiberscope without having to perform a re-median sternotomy. The technique of endoscopic removal of cardiac surgical misplacement is described. PMID- 7772925 TI - Thoracoscopic sympathectomy for Buerger's disease: a report on the successful treatment of four patients. AB - We describe herein the successful treatment of four patients with ischemic ulcers or gangrene of the fingers due to Buerger's disease by thoracoscopic sympathectomy, a new method of surgery which eliminates the difficulties associated with the traditional "open" approaches to the thoracic sympathetic chain, such as poor exposure, risk of damage to the adjacent structures, and postoperative pain. After the patients were placed in the lateral decubitus position with unilateral pulmonary ventilation, the thoracic sympathetic ganglia (T) from the lower third of T1 to T3 were resected endoscopically. The operative results were excellent, with improvement or complete resolution of the ulcer being achieved in all four patients. All of the patients were satisfied with the results in terms of ulcer healing, postoperative pain, and cosmetic appearance. Although a postoperative air leakage developed in one patient with a history of pulmonary tuberculosis, it was successfully treated with an adhesive agent. None of the patients developed Horner's syndrome. Thus, because thoracoscopic sympathectomy is easier to perform with a lower risk of complications than conventional thoracic sympathectomy, we recommend this operative approach as the procedure of choice for surgical thoracic sympathectomy. PMID- 7772926 TI - The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines. AB - The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10-40 microM dose dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer. PMID- 7772927 TI - Terminal motor latency in the pudendal nerves after colectomy with mucosal proctectomy and ileal J pouch-anal anastomosis for ulcerative colitis. AB - Pudendal nerve terminal motor latencies (PNTML) were measured in eight patients with ulcerative colitis who underwent colectomy with mucosal proctectomy and ileal J pouch-anal anastomosis, using a new digitally directed transrectal stimulation and recording technique, and the results were compared with data obtained from 15 control subjects. The conduction delay of PNTML in the patients with some degree of fecal incontinence was the longest, followed by those without any incontinence, and then the control subjects. These findings support the hypothesis that fecal incontinence after this procedure may be partially caused by damage to the pudendal nerve. PMID- 7772929 TI - AHNA certificate program in holistic nursing courses: AHNA certificate program in healing touch courses. PMID- 7772930 TI - Is there a scent in your future? PMID- 7772928 TI - Complex abdominal and thoracoabdominal aortic aneurysm reconstruction. AB - Complex reconstructions of the abdominal aorta are required for aneurysms that require visceral or splanchnic revascularization, when the aorta is inflammatory or infected, when a fistula to the vena cava or bowel is present, and when the aneurysm involves the juxtarenal, pararenal segments, or the full length of the abdominal aorta. The technique for full-length abdominal and thoracoabdominal aortic reconstructions has been modified to separate the visceral and spinal cord revascularization from the body of the main graft. The visceral, renal, and intercostal arteries are not directly reimplanted into the aortic graft but rather into sidearm grafts using a patch inclusion technique. The reconstruction commences distally by anastomosing the main graft to the aortic bifurcation or to the iliac arteries as appropriate. The main graft is then anastomosed to the proximal aorta after which the aortic clamps are released to perfuse the lower limbs. The intercostal arteries are reimplanted into a posterior sidearm graft followed by visceral and renal artery reimplantation into an anterior sidearm graft. This technique reimplantation into an anterior sidearm graft. This technique reduces the period of left ventricular strain to the time taken to complete the upper aortic anastomosis. It also allows separate control of the visceral and intercostal implantations should bleeding occur, without the necessity to reclamp the main body of the graft. PMID- 7772931 TI - On holism--accepting one another. PMID- 7772932 TI - AHNA certificate program in holistic nursing courses; AHNA certificate program in healing touch courses. PMID- 7772933 TI - When we really discover the world is round ... we can no longer choose sides. PMID- 7772934 TI - Differential perceptions, behaviors, and motivations among African Americans, Latinos, and whites suspected of heart attacks in two hospital populations. AB - To evaluate the hypothesis that socioeconomic status would exert greater influence on patients' care-seeking behavior than racial/ethnic group status, we undertook a sequential study of African-American, Latino, and white patients hospitalized for acute chest pain from August 1988 through July 1990 at two sites. The study took place in an urban public medical center and an urban private health maintenance organization medical center, which provide care to mixed racial/ethnic groups of lower and middle socioeconomic status, respectively, in Los Angeles. Three concurrent case series of African-American, Latino, and white patients hospitalized for acute chest pain were recruited. The racial/ethnic distribution of the total group was African Americans, 448; Latinos, 487; and whites, 499. The main outcome measure was the length of time patients spent in deciding to seek emergency medical care for acute chest pain and the associated perceptions, behaviors, and motivations involved in deciding to seek care. For the total group, public hospital site and lack of health insurance were the strongest significant predictors of a longer decision phase, whereas differential symptom perceptions, consultation with medical professionals, and use of paramedic transport were significant predictors of shorter duration. Multiple regression results were similar in separate analyses demonstrated significant differences in patients' perceptions of symptom intensity and incapacitation within racial/ethnic groups related to socioeconomic status, as well as in specific behavior and motivation in seeking care. The study concluded that socioeconomic status as determined by hospital site exerted a stronger influence on patients' care-seeking behavior for acute chest pain than racial/ethnic status. Specific care-seeking behaviors of minority and lower socioeconomic-status patients in the use of medications and paramedics in the face of acute symptoms should be targeted in future educational programs. PMID- 7772935 TI - Variations in oral glucose tolerance tests: the 100- versus 75-g controversy. AB - This study compared the results of a 75-g, 3-hour oral glucose tolerance test with those of a traditional 100-g oral glucose tolerance test. Thirty-two pregnant women participated in the study. Each patient served as her own control, undergoing both a 100- and a 75-g oral glucose tolerance test within 1 week. Despite a strong positive correlation between the results of the two tests, the 1 , 2-, and 3-hour glucose values of the 100-g glucose load were significantly higher than the comparable values of the 75-g oral glucose tolerance test. Sixteen of 32 women were diagnosed as having gestational diabetes mellitus using the National Diabetes Data Group criteria and the 100-g oral glucose tolerance test, whereas only 6 of these 16 women would have been identified with the 75-g oral glucose tolerance test. If data from one test are to be compared with the other, new thresholds of glucose abnormality need to be developed. PMID- 7772936 TI - Cultural diversity as a factor in self-monitoring blood glucose in gestational diabetes. AB - The routine use of self-monitoring of capillary blood glucose by pregnant diabetic patients currently provides the basis for both clinical management and ongoing investigation. Strategies must therefore be developed to ensure that these data are reliable and accurately reported by patients and are not influenced by diverse socioeconomic levels or varied geographic locations. To explore this issue, we used glucose reflectance meters with a memory microchip capable of storing up to 440 consecutive blood glucose determinations. Two diverse groups of women from Texas and New York who had gestational diabetes performed self-monitoring of blood glucose from diagnosis until delivery. Both groups recorded their blood glucose results daily in a logbook. The reporting performance of all the participating subjects resulted in an actual compliance rate of 60% to 70% of testings required of the patients. Comparison of African American, Mexican-American, and white populations revealed no significant differences in patient performance or compliance. Moreover, no differences were found between the groups at different geographic locations (New York, Texas) in patients' willingness and ability to comply with the regimen of self-monitoring blood glucose. These findings suggest that the use of memory reflectance meters, in conjunction with patient education and positive interaction between patient and care provider, will result in high patient compliance regardless of socioeconomic level or ethnic diversity. PMID- 7772937 TI - Impact of an inner-city, hospital-based preterm prevention program on preterm births in twin gestation. AB - The objective of this study was to determine the impact of an inner-city, hospital-based preterm-birth prevention program on the outcome of twin pregnancies. A retrospective study of delivery outcomes from 1985 to 1992 of eligible consecutive twin deliveries that were > or = 20 weeks' gestation compared two inner-city hospitals in the Bronx, New York: one with a preterm prevention program for twin births and a comparable site offering conventional prenatal care. A group of patients receiving no prenatal care was also included. Outcomes were evaluated by prenatal-care site, except for those who received no prenatal care and delivered at either site. Data were analyzed by chi-square analysis and analysis of variance. Of the 377 twin pregnancies, 330 pregnancies were eligible deliveries. One hundred thirty-four women received prenatal care from the preterm prevention program, 161 received conventional prenatal care at a comparable site, and 35 received no prenatal care. Maternal age, parity, and mode of delivery were similar in the two delivery sites. There was an increased incidence of complications in the no-prenatal-care group compared with the groups who received the preterm prevention or conventional prenatal care. The percentage of low-birth-weight (< 2500 g) and very-low-birth-weight (< 1000 g) infants was similar in the preterm prevention and the conventional care groups. The percentage of extremely low-birth-weight (< 1000 g) infants was significantly lower in twin births of the preterm prevention site (9.7%) and the conventional site (11.3%) compared with the no-prenatal-care group (28.6%) (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772938 TI - Metabolism of halohydroquinones in Rhodococcus chlorophenolicus PCP-1. AB - The actinomycete Rhodococcus chlorophenolicus PCP-1 metabolizes pentachlorophenol into ultimate inorganic end products via tetrachloro-p-hydroquinone. This intermediate was further dehalogenated in the cytoplasm requiring reductant in the cell free system. Tetrafluoro-p-hydroquinone and tetrabromo-p-hydroquinone were also dehalogenated. Chlorophenol analogs, thiol blocking agents and molecular oxygen inhibited the activity. The dehalogenating reactions led to 1,2,4-trihydroxybenzene, which was further metabolized into maleic acid. PMID- 7772939 TI - Effects of oxygen, nitrogen, and temperature on gasoline biodegradation in soil. AB - Biodegradation was considered to be a feasible approach to remediate petroleum hydrocarbon-contaminated soil from a site at the University of Idaho. Before a full-scale treatment process was designed, the biodegradative capacity of the soil's indigenous microorganisms was tested. Gas chromatography was used to measure gasoline vapor components in the headspace above the contaminated soils held in closed containers. In a study of biodegradation kinetics, gasoline degradation rates under various conditions (different soil cores, temperatures, oxygen concentrations, and nutrient concentrations) were tested. It was found that gasoline hydrocarbons could be biodegraded at relatively high rates after appropriate nutrient additions. An unexpected observation was that the optimal concentration of oxygen for the gasoline-degrading microorganisms in these soils was only 10%. PMID- 7772940 TI - Transformation of o-xylene to o-methyl benzoic acid by a denitrifying enrichment culture using toluene as the primary substrate. AB - A highly enriched denitrifying mixed culture transformed o-xylene co metabolically along with toluene by methyl group oxidation. o-Methyl benzaldehyde and o-methyl benzoic acid accumulated transiently as metabolic products of o xylene transformation. Transformation of o-methyl benzyl alcohol and o-methyl benzaldehyde occurred independently of toluene degradation and resulted in the formation of a compound coeluting with o-methyl benzoic acid on a gas chromatograph. The co-metabolic relationship between toluene and o-xylene could be attributed to a mechanism linked to the initial oxidation of the methyl group. PMID- 7772941 TI - Stoichiometry and kinetics of microbial toluene degradation under denitrifying conditions. AB - Batch experiments were carried out to investigate the stoichiometry and kinetics of microbial degradation of toluene under denitrifying conditions. The inoculum originated from a mixture of sludges from sewage treatment plants with alternating nitrification and denitrification. The culture was able to degrade toluene under anaerobic conditions in the presence of nitrate, nitrite, nitric oxide, or nitrous oxide. No degradation occurred in the absence of Noxides. The culture was also able to use oxygen, but ferric iron could not be used as an electron acceptor. In experiments with 14C-labeled toluene, 34% +/- 8% of the carbon was incorporated into the biomass, while 53% +/- 10% was recovered as 14CO2, and 6% +/- 2% remained in the medium as nonvolatile water soluble products. The average consumption of nitrate in experiments, where all the reduced nitrate was recovered as nitrite, was 1.3 +/- 0.2 mg of nitrate-N per mg of toluene. This nitrate reduction accounted for 70% of the electrons donated during the oxidation of toluene. When nitrate was reduced to nitrogen gas, the consumption was 0.7 +/- 0.2 mg per mg of toluene, accounting for 97% of the donated electrons. Since the ammonia concentration decreased during degradation, dissimilatory reduction of nitrate to ammonia was not the reductive process. The degradation of toluene was modelled by classical Monod kinetics. The maximum specific rate of degradation, k, was estimated to be 0.71 mg toluene per mg of protein per hour, and the Monod saturation constant, Ks, to be 0.2 mg toluene/l. The maximum specific growth rate, mu max, was estimated to be 0.1 per hour, and the yield coefficient, Y, was 0.14 mg protein per mg toluene. PMID- 7772942 TI - Tetrachloroethene and 3-chlorobenzoate dechlorination activities are co-induced in Desulfomonile tiedjei DCB-1. AB - Desulfomonile tiedjei, a strict anaerobe capable of reductively dechlorinating 3 chlorobenzoate, also dechlorinates tetrachloroethene and trichloroethene. It is not known, however, if the aryl and aliphatic dechlorination activities are catalyzed by the same enzymatic system. Cultures induced for 3-chlorobenzoate activity dechlorinated tetrachloroethene and trichloroethene to lower chlorinated products while uninduced parallel cultures did not dechlorinate either substrate. The observed rate of PCE dechlorination in induced cultures was 22 mumol h-1 g protein-1, which is considerably faster than previous rates obtained with defined cultures of this organism. These results show that both dechlorination activities are co-induced and therefore, that the dechlorination mechanisms may share at least some components. PMID- 7772943 TI - Biotransformation of diphenyl ether by the yeast Trichosporon beigelii SBUG 752. AB - Trichosporon beigelii SBUG 752 was able to transform diphenyl ether. By TLC, HPLC, GC, GC-MS, NMR- and UV-spectroscopy, several oxidation products were identified. The primary attack was initiated by a monooxygenation step, resulting in the formation of 4-hydroxydiphenyl ether, 2-hydroxydiphenyl ether and 3 hydroxydiphenyl ether (48:47:5). Further oxidation led to 3,4-dihydroxydiphenyl ether. As a characteristic product resulting from the cleavage of an aromatic ring, the lactone of 2-hydroxy-4-phenoxymuconic acid was identified. The possible mechanism of ring cleavage to yield this metabolite is discussed. PMID- 7772944 TI - Degradation of 4-chloro-2-methylphenol by an activated sludge isolate and its taxonomic description. AB - The Gram-negative strain S1, isolated from activated sludge, metabolized 4-chloro 2-methylphenol by an inducible pathway via a modified ortho-cleavage route as indicated by a transiently secreted intermediate, identified as 2-methyl-4 carboxymethylenebut-2-en-4-olide by gas chromatography/mass spectrometry. Beside 4-chloro-2-methylphenol only 2,4-dichlorophenol and 4-chlorophenol were totally degraded, without an accumulation of intermediates. The chlorinated phenols tested induced activities of 2,4-dichlorophenol hydroxylase and catechol 1,2 dioxygenase type II. Phenol itself appeared to be degraded more efficiently via a separate, inducible ortho-cleavage pathway. The strain was characterized with respect to its physiological and chemotaxonomic properties. The fatty acid profile, the presence of spermidine as main polyamine, and of ubiquinone Q-10 allowed the allocation of the strain into the alpha-2 subclass of the Proteobacteria. Ochrobactrum anthropi was indicated by fatty acid analysis as the most similar organism, however, differences in a number of physiological features (e.g. absence of nitrate reduction) and pattern of soluble proteins distinguished strain S1 from this species. PMID- 7772945 TI - The development of a novel strategy for the microbial treatment of acrylonitrile effluents. AB - Effluent from the manufacture of acrylonitrile is difficult to biodegrade. It contains nine major organic components: acetic acid, acrylonitrile, acrylamide, acrylic acid, acrolein, cyanopyridine, fumaronitrile, succinonitrile, and maleimide. A range of bacteria have been isolated that can grow on, or convert all of the organic components of effluent from the manufacture of acrylonitrile. These bacteria can be used as the basis of a mixed culture system to treat the effluent. The bacteria were utilised in batch and continuous cultures to degrade a synthetic wastewater containing acrylonitrile, acrylamide, acrylic acid, cyanopyridine and succinonitrile. The mixed microbial population was adapted by varying the growth rate and switching from continuous to batch and back to continuous growth, to degrade these five compounds as well as acrolein, fumaronitrile and maleimide. PMID- 7772946 TI - Purification of virus like particles from yeast cells using aqueous two-phase systems. AB - Aqueous two-phase systems have been used for the separation and purification of recombinant virus-like particles (VLPs) from a yeast cell homogenate. Systems have been evaluated on the basis of their ability to separate VLPs from cell debris and from contaminating proteins. Two strategies are proposed for VLP separation, both involve the use of two PEG/salt aqueous two-phase systems. For separation of VLPs from cell debris systems composed of PEG 400 or 600 and (NH4)2SO4 or PEG 4000/MgSO4 can be used and for separation of VLPs from proteins PEG 4000/(NH4)2SO4 or MgSO4 and Na2SO4 are effective. The molecular weight of the PEG used and the use of additional salts (e.g. NaCl) greatly influence the effectiveness of the systems. PMID- 7772947 TI - Use of multifactorial analysis to develop aqueous two-phase systems for isolation of non-native IGF-I. AB - A high yield procedure was developed to solubilize and extract IGF-I from recombinant E. coli by adding chaotrope and disulfide reductant to alkaline fermentation broth. To enhance centrifugation performance and recovery yield, a salt/polymer aqueous two-phase extraction procedure was developed whereby soluble non-native IGF-I and biomass solids are enriched in separate liquid phases. To develop this extraction system a multifactorial experimental approach was used to simultaneously map the phase diagram and identify conditions to suitably partition IGF-I and cell remnants. The presence of urea in these systems tended to disrupt two-phase formation and solids sedimentation. This, in turn, constrained the concentrations of phase forming solutes which could be effectively used. Systems containing low levels of salt (less than about 4% w/w) and polymer (less than about 10% w/w) did not form two phases. Systems containing high levels of salt (greater than about 7% w/w) and polymer (greater than about 18% w/w) formed two phases with floating solids. Intermediate levels of salt (between about 4% and 7% w/w) and polymer (between about 10% and 18% w/w) formed two phases in which solids were enriched in the heavy phase. Systems in this latter desired category were produced with a variety of different salts and polymers and all enriched non-native IGF-I in the light phase. Highest recovery yield (about 90%) was obtained with systems composed of 5% sodium sulfate and 14% PEG-8000.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772948 TI - Synthesis of thiophilic adsorbents, containing amine spacer arms, and adsorption of immunoglobulins from adult bovine serum. AB - In order to remove immunoglobulins from adult bovine serum (ABS), adsorptions were carried out in suspension with thiophilic adsorbents without (T-gel) and with (ST-gels) short amine spacer. The developed ST-gels could be cleaned in sodium hydroxide and specifically adsorbed immunoglobulins from ABS at a lower ionic strength of the adsorption buffer than a T-gel. The ST-gels are suited for the performance of adsorptions in a suspension with a high concentration of the adsorbent. For an almost complete removal of immunoglobulins from ABS in 0.5 M potassium sulfate and 0.1 M potassium phosphate (pH 7), up to 75 g ST-gel per 1 suspension may process up to 100 ml ABS. The synthesized ST-gels contained an equal amount of amine spacers and sulfone groups. The ratio between coupled 2 mercaptoethanol molecules and sulfone groups was about 0.4. In comparison with the T-gel, the chemical stability of the ST-gels in solutions of 0.1 to 1 M sodium hydroxide was higher. The capacity for adsorbing pure immunoglobulins of the T-gel was 0.329 g g-1 (10.9 g l-1) and of the ST2-gel, 0.677 g g1 (52.3 g l 1). The capacity for adsorbing IgG from ABS of the T-gel was 0.177 g g1 (5.88 g l 1) and of the ST2-gel, 0.152 g g-1 (11.7 g l-1). This reduced capacity was attributed to a low affinity binding to the adsorbents of other proteins from ABS. When an incubation of the adsorbent with ABS was performed in 0.5 M potassium sulfate and 0.1 M potassium phosphate (pH 7), the affinity constant (Ka) for IgG of the T-gel was 2.5 x 10(6) M-1 and of the ST-gel, 3.1 x 10(7) M-1. In this adsorption buffer at a protein concentration above 5 g l-1, salt-promoted precipitation of IgG took place. When an adsorption was performed at the minimal ionic strength of the adsorption buffer, the Ka of the T-gel for IgG was about 9 x 10(3) M-1 and of the ST-gel, about 2.3 x 10(5) M-1. In this case, the removal of Igs from ABS was achieved by means of a partition equilibrium, rather than by high affinity adsorption. PMID- 7772949 TI - Preparation of high purity alkaline phosphatase from calf intestine using dye ligand chromatography. AB - For the effective application of alkaline phosphatase from calf intestine in Molecular Biology research highly purified enzyme and free from contaminating DNases, DNA nicking, ribonuclease and phosphodiesterase activities is required. We now report the use of a two-step procedure which involves chromatography on a Mimetic Blue AP-Agarose, a commercially available adsorbent and Heparin Sepharose to purify calf intestinal alkaline phosphatase from a crude commercial preparation to homogeneity. Purified enzyme preparations were free from contaminating DNases, DNA nicking, ribonuclease and phosphodiesterase activities and exhibited a specific activity (3.800 units/mg) which is one of the highest reported among the existing high purity commercial preparations. It is therefore concluded that the reported purification protocol can be used routinely to prepare high purity alkaline phosphatase suitable for use in Molecular Biology research. PMID- 7772950 TI - Purification of human interleukin-2 using the cellulose-binding domain of a prokaryotic cellulase. AB - Engineering gene fusions which introduce an affinity tag linked to the target polypeptide by a specific protease cleavage site is widely used to facilitate recombinant protein purification. A fusion protein CBDAPT-IL-2, comprised of the cellulose-binding domain (CBD) and Pro-Thr (PT) rich linker of the Cellulomonas fimi endo-beta-1,4-glucanase A (CenA) and a factor Xa cleavage sequence (IleGluGlyArg) fused to the N terminus of human interleukin-2, was produced in Escherichia coli, Streptomyces lividans and mammalian COS cells. CBDAPT-IL-2, secreted from S. lividans or COS cells or recovered from the insoluble fraction of E. coli, could be purified by adsorption on cellulose. The intact fusion protein adsorbed to cellulose was hydrolyzed in situ with factor Xa to release active interleukin-2. PMID- 7772952 TI - Nurse-patient communication in intensive care: a low priority? AB - Nursing literature is well endowed with information supporting the importance of maintaining optimal communication between nurses and critically ill patients (Rundell 1991). There is, however, evidence to suggest that although critical care nurses are aware of the need to communicate effectively with their patients, this often does not occur (Mallett 1990). PMID- 7772951 TI - Caring for children in an adult intensive care unit--Part I. AB - Various reports draw attention to the deficiency of services available for critically ill children. In December 1993 the British Paediatric Association published a report by a multidisciplinary working party on intensive care. The Minister of Health has apparently promised to act on the recommendations the working party made. In fact, purchasers are being encouraged to act and ask questions about the provision of paediatric intensive care--but no extra funding is available to provide it. However, this will all take time and until more resources are available children are still being cared for on adult intensive care units by nurses who may not be experienced in caring for sick children. One of the main areas of concern nurses have when caring for children is the physiological differences between an adult and a child. This paper is designed to assist in identifying the differences and consequent nursing implications. In an attempt to prioritize the nursing care a systems/modified model has been used over 2 papers. The review of the systems demonstrates the differences between adults and children and, where possible, highlights the nursing care and medical treatment a child requires. All aspects of care have been included as well as the psychological problems (see Part 2 which will be published in the next issue) encountered by the family of a critically ill child. Where possible easy reference tables have been included and the author hopes to introduce the package into the existing orientation programme for established staff and staff new to the unit in the hopes of decreasing the stress when a child is admitted. Paediatric resuscitation has not been covered intentionally, as the information on the physiological differences seemed to grow like 'Jack's beanstalk'. Therefore, a flow chart for basic and advanced life support is included as an appendix in Part I. It is hoped this will stimulate readers' interest for more in depth study. PMID- 7772954 TI - BACCN position statement: resourcing of intensive care services. PMID- 7772953 TI - Research and practice development. PMID- 7772955 TI - What of intensive care? PMID- 7772956 TI - Recognising post-traumatic stress in intensive care patients. AB - 'We may not be able to prevent stress or distress, but we can alter the intensity and duration of stress-related trauma by naming our demons, daring to struggle with them, and by creating healing communities.' (Chandler 1992, p 88) In order to create an environment in which the above process can take place it is incumbent upon nurses to assess patients in need and to institute appropriate intervention at an early stage. Critical care nurses have a particular responsibility to identify the seeds of post-traumatic stress and implement supportive and preventive strategies, primarily because of the numbers of traumatised victims passing through their care. Even so, there appears to be a dearth of critical care literature which addresses either assessment or intervention strategies relevant to this important aspect of practice. The purpose of this paper is to highlight aspects of assessment specific to post traumatic stress through a critical analysis and explanation of its theoretical base. This will act as a precursor to providing direction on possible practice developments. PMID- 7772958 TI - A rationale for mouth care: the integration of theory with practice. AB - Mouth care is a commonly performed nursing procedure in which the aim is to ensure that patients' mouths are cared for. However, there is evidence that unless dental plaque is removed from the tooth surfaces and the gingival margin, the mouth is in danger of becoming unhealthy and, therefore, uncared for. It appears from the dental literature that the use of a toothbrush is one of the best and most widely used tools in the Western world for removing dental plaque (Addy, Slayne & Wade 1992), other methods being ineffective, dangerous, or poorly researched (Trenter-Roth & Creason 1986). However, a review of the nursing literature indicates that toothbrushes are not the tools of choice for mouth care by nurses (Howarth 1977, Harris 1980). Thus, there appears to be a gulf between the knowledge base from the dental literature and the reality of nursing practice resulting in 'mouth care' becoming a misleading misnomer. The aim in this paper is to present a rationale for mouth care based upon the dental literature and to apply such knowledge to nursing practice, especially in intensive therapy units (ITUs), so that nurses may be in a better position to provide 'mouth care' which lives up to its name. PMID- 7772957 TI - A comparative descriptive study of patients admitted to a high dependency unit after major and non-major surgery. AB - Monash Medical Centre, a large major hospital in Melbourne Australia, recently opened a high dependency unit (HDU) at its Moorabbin campus. The present study was designed to examine two patient groups admitted to the unit after major and non-major surgical procedures. Another aim in the study was to describe the services required by these patients and to compare the two groups with regard to length of stay in the HDU, severity of illness, and pain control. The results of this study indicate that the HDU provided a valuable and needed service to a population of patients who have been identified as at risk of postoperative complications. The findings appear to agree with other research which suggests that nurses consistently rate patients' pain as less severe than patients' own ratings of pain indicate. Thus nurses appear to overestimate patients' perception of pain control. This study again indicates that even though it is generally recognised by nurses that patients are in pain the management of it is such that pain continues to be inadequately controlled. PMID- 7772959 TI - A qualitative study to establish the self-perceived needs of family members of patients in a general intensive care unit. AB - Admission to an intensive care unit (ICU) invariably causes a considerable degree of distress and anxiety to both patient and family. If we profess to deliver holistic care then it is essential that intensive care nurses are able to identify the specific needs of family members and provide appropriate supportive interventions. This small study was designed to gain the perspectives of the families. Through unstructured interviews participants were invited to discuss their experiences of visiting a critically ill relative, particularly in relationship to their own needs. Interviews were tape-recorded with permission and subsequently transcribed. Thematic content analysis adapted from Glaser & Strauss' 'grounded theory' approach (1967) by Burnard (1991) occurred, with formation of six categories, exemplified by verbatim quotations. The study may contribute towards a framework for preventative, supportive and therapeutic intervention with family members in the intensive care setting. PMID- 7772960 TI - Responsibility in intensive care: a critical analysis. AB - Nursing has undergone numerous aspects of change within the last 10 years, resulting in a blurring of roles and thus responsibilities. Responsibility in nursing is an enormous, vitally important and pertinent concept. In this paper the term 'responsibility' will be described, discussed and critiqued within the context of the management of care, research and education for nurses working in an intensive care environment. PMID- 7772961 TI - Education in critical care nursing: a new beginning. AB - The movement of nurse education to the tertiary sector is all but complete in Australia. Trends are changing as new partnerships are being forged and the focus of education is now reponsive to economic and political factors. These factors have resulted in the regionalisation of health care facilities and the de institutionalisation of health services in Queensland. Moreover, de institutionalisation of services coupled with economic rationalism has pre-empted the offering of post-graduate clinical courses by university nursing faculties. This paper addresses the process of developing the content of new courses under the umbrella of the Graduate Diploma/Masters in Critical Care Nursing offered at Griffith University Gold Coast. This initiative is the first in Queensland and has provided new vision in education for critical care nursing. This course includes a tapestry of theoretical knowledge enhancing clinical and factual subjects presented by experienced clinicians teaching with academics. The collaborative nature of nursing practice is reflected in academics and clinicians working jointly in course development, teaching and clinical placement. Strategies which were developed collaboratively addressed course content including logistics, time management, the critical selective selection of appropriate content, assessment critera, 'registerbility' within Queensland and other states, and clinical competence will be addressed. Moreover, this process of developing the course content utilised Australian National Registering Authority (ANRAC 1990) Competencies and Benners' (1984) use of the Dreyfus model to guide the expected knowledge level of the clinician at course completion. In particular this paper will not only address the blending of theory and practice to consolidate the relationship inherent between the clinician and education, but will establish the fact that no gap exists. PMID- 7772962 TI - Anesthesia for stereotactic radiosurgery in children. AB - The development of stereotactic radiosurgery has been a major advance in the treatment of intracranial lesions. By using a stereotactic head frame attached to the skull, large doses of radiation can be delivered precisely to the lesion while sparing surrounding tissues. Although adults can usually undergo this procedure with local anesthesia or conscious sedation alone, children frequently require general anesthesia. This report describes our experience with the anesthetic management of all children who have received this therapy at our institution since the inception of our stereotactic radiosurgery program in 1986 through June 1993. Sixty-eight radiosurgery procedures were performed in 65 patients. Anesthesia time averaged 9.2 h (range, 7-15). Twenty-two patients (ages 11-17; mean 14.3) received local anesthesia alone, two patients (ages 11 and 15) received local anesthesia plus i.v. sedation, and 44 patients (ages 2-14; mean, 7.3) received general anesthesia. Four potentially serious anesthesia-related events occurred; in one child (age 7) receiving general anesthesia, an endotracheal tube obstruction developed during radiosurgery requiring rapid reintubation while the child was still in the head frame; another (age 7) who was undergoing chemotherapy and had neutropenia and rhinitis had a lobar collapse while intubated, requiring mechanical ventilation and endotracheal tube suctioning for lung expansion. Another (age 5) with a recent upper respiratory tract infection had copious endotracheal secretions and sinusitis (ethmoid and maxillary) noted on initial computed tomography scanning and was given antibiotics and decongestants (following nasotracheal extubation), and another (age 15) receiving sedation without endotracheal intubation vomited an undigested meal midway through the procedure while her head was partially immobilized in the head frame.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772963 TI - Regional cerebral metabolism of glucose in comatose and vegetative state patients. AB - Regional cerebral metabolism of glucose (rCMRglu) was evaluated in patients who were in a coma and vegetative state to determine the level of brain function during these conditions. rCMRglu was measured in 17 discrete brain regions with (/-) [18F] -fluoro-2-deoxy-D-glucose (FDG) and positrn emission tomography (PET) in 15 patients with ;brain pathology subsequent to cardiorespiratory arrest (CA), head trauma (HT), or brain ischemia (BI) resulting from cerebrovascular accident or brain surgery. Five comatose patients (Coma group, n = 5), and 10 vegetative state patients (VS, patients awake but not aware) were studied. The VA patients were subdivided, according to the length of their VS condition, into a VS group (n = 6, < 3 months if CA or BI patients, or < 12 months if HT patients) and a persistent vegetative state group (PVS, n = 4, > 3 months if CA or BI patients of > 12 months if HT patients.) Ten normal age-matched subjects served as control. Global CMRglu was 6.72 +/- 0.93 (+/-SD) mg/100 g/min in control subjects. It was significantly (p < - 0.001) reduced to 3.70 +/- 61 in coma, to 3.45 +/- in VS, and to 2.33 +/- 0.34 mg/100 g/min in PVS patients. rCMRglu was significantly reduced (p < - 01001) from control values in all the 17 structures surveyed in every patient. In the Coma and VS groups, there was an overlapping of rCMRglu in the majority of the brain structures. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772964 TI - Indomethacin in controlling "normal perfusion pressure breakthrough" in a case of large cerebral arteriovenous malformation. AB - Control of "normal perfusion pressure breakthrough" is difficult and controversial. We describe a case in which indomethacin was used with success. We recommend extensive cerebral monitoring including regional cerebral oximetry when using indomethacin to detect impending cerebral ischemia. PMID- 7772965 TI - Perforation and partial obstruction of an armored endotracheal tube. AB - Armored endotracheal tubes are often used during cases in which there is a risk of compromise of a polyvinylchloride tube with positioning of a patient's head. The authors describe a case in which partial airway obstruction and perforation of such a tube occurred as a result of biting by a patient. Ways to avoid this complication are discussed. PMID- 7772966 TI - Preoperative evaluation for risk of venous air embolism in the sitting position. AB - We report a patient with meningioma and radiological findings of erosive bony change, who developed venous air embolism via the diploic vein in the eroded inner table of the skull during craniotomy in the sitting position. The findings in our case suggest that preoperative radiological imaging evaluation can increase an awareness of the possibility of venous air embolism. PMID- 7772967 TI - Control of outflow pressure provides spinal cord protection during resection of descending thoracic aortic aneurysms. PMID- 7772968 TI - Side effects of mild hypothermia. AB - Mild hypothermia is increasingly touted as a low risk clinical measure in brain protection. This article reviews potential adverse effects of mild hypothermia by organ system and suggests a risk assessment framework for clinical decision making. PMID- 7772969 TI - Inhibition of glutamate release: a possible mechanism of hypothermic neuroprotection. AB - The neuroprotective properties of hypothermia are well recognized. For many years, the ability of hypothermia to decrease the neurologic morbidity associated with episodes of ischemia has been ascribed to the reduction in metabolic rate that accompanies decreases in temperature. More recently, evidence has accumulated that hypothermia may exert some of its neuroprotective effects by reducing the ischemia-induced release of excitatory amino acids. This attenuated release occurs even with the mild degrees of hypothermia that can easily be produced in operating rooms and intensive care units. Preliminary data suggest that mild hypothermia may be of benefit in surgical patients at risk for intraoperative cerebral ischemia and patients who have suffered traumatic brain injury. Because of the minimal risk associated with lowering body temperature to 34 degrees C, additional outcome studies are in progress to ascertain the potential benefits of this mode of therapy. PMID- 7772970 TI - Systemic hypothermia in treatment of severe brain injury. PMID- 7772971 TI - N2O: of questionable value. PMID- 7772972 TI - Nitrous oxide added to isoflurane increases brain artery blood flow and low frequency brain electrical activity. AB - Although changes in cerebral blood flow (CBF) and the electroencephalogram (EEG) have been reported with nitrous oxide (N2O) administration, the interaction of these parameters is unclear. The purpose of this study was to measure CBF and EEG during N2O administration in eight patients. A craniotomy was performed and CBF was measured in major brain arteries using a transit time Doppler flowmeter. EEG was recorded bilaterally from frontooccipital leads. Power spectrum analysis was performed on the EEG and power for delta, theta, alpha, and beta frequency bands analyzed over time. Arterial blood pressure was recorded continuously. N2O (66%) was added to the inspired gases during isoflurane anesthesia (0.8% end tidal) under hypocapnic (Paco2 = 29 mm Hg) and normocapnic conditions (Paco2 = 39 mm Hg). During hypocapnia, N2O administration decreased alpha EEG activity and increased delta activity but did not change CBF. During normacapnia, N2O produced similar but greater changes in EEG and increased CBF 39%. In three patients, the isoflurane concentration was increased to 1.6% end tidal during normocapnia. N2O administration in these patients also enhanced delta EEG activity and increased CBF. The slowing of EEG activity with N2O is temporally related to increases in CBF during normocapnia. Hypocapnia abolished the increase in CBF during N2O and attenuated the shift of EEG to delta activity. PMID- 7772973 TI - Nitrous oxide increases cerebral blood flow velocity during pharmacologically induced EEG silence in humans. AB - We examined the effect of nitrous oxide on cerebral blood flow velocity (Vmca), arteriovenous oxygen content difference and cerebral use of glucose during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients undergoing anesthesia for nonneurosurgical procedures. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 3 micrograms/kg (followed by an infusion of 2 micrograms/kg/h), vecuronium 0.1 mg/kg, and maintained with a propofol infusion (250-300 micrograms/kg/min) sufficient to induce EEG silence. A transcranial Doppler was used to measure the Vmca and a jugular bulb catheter was inserted for oxygen saturation and glucose use measurements. After a 15-period of isoelectric EEG and normocapnia (PaCO2 38 +/- 1 mm Hg), baseline arterial and jugular bulb venous blood gases were drawn, and mean arterial pressure (MAP), heart rate (HR), and Vmca were recorded. Nitrous oxide was then introduced and equilibrated to an end-tidal concentration of 70% for 15 min, after which MAP, HR, Vmca, arterial and jugular bulb venous blood gases were measured again. Nitrous oxide increased Vmca (29 +/- 4 to 35 +/- 4 cm/s, p < 0.01), cerebral use of oxygen (166 +/- 13 to 190 +/- 12 vol%-cm/s, p < 0.05) and glucose (245 +/- 38 to 290 +/- 48 g%-cm/s, p < 0.05) by approximately 20%. Occasional bursts of EEG activity were observed in eight patients studied during the N2O stage. We conclude that in patients with propofol-induced isoelectric EEG, the increase seen in Vmca with the introduction of N2O is mainly due to cerebral stimulation and increase in cerebral metabolic rate. PMID- 7772974 TI - A comparison of anesthetic techniques for awake intubation in neurosurgical patients. AB - Two different methods of achieving upper airway anesthesia for awake fiberoptic intubation were prospectively compared in patients undergoing surgery for cervical spine instability. Forty patients were randomized to either topical anesthesia or nerve block groups. Topical anesthesia patients were administered nebulized 4% lidocaine (approximately 20 ml) via the oropharynx plus a transtracheal injection of 4% lidocaine (3 ml). Nerve block patients underwent bilateral glossopharyngeal and superior laryngeal nerve blocks with 2% lidocaine (0.5-2 ml per injection site) plus a transtracheal injection of 4% lidocaine (3 ml). The quality of anesthesia for intubation was graded by observers blinded to group assignment. Mean arterial pressure, heart rate, Pao2, Paco2, pHa, SpO2, and plasma lidocaine concentrations were measured during the intubation sequence. Patient recall of intubation and discomfort were assessed during the postoperative period with visual analog scales. Time required for successful intubation and quality of intubation were not different between groups. Physiologic values for the two groups were similar. The mean total dose of lidocaine in the topical anesthesia group was approximately 2 times greater than that in the nerve block group (815 versus 349 mg; p < 0.0001). In contrast, mean plasma lidocaine concentration at initiation of intubation in the topical anesthesia group was half that of nerve block group (2.16 versus 4.23 micrograms/ml; p < 0.0001). Ten minutes later there was no difference for plasma lidocaine concentration between groups. No patients had evidence of seizures or neurologic change during the procedure. There was no difference in patient perception of discomfort during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7772975 TI - BMA reports on the declining standards in community care. PMID- 7772976 TI - Delivering quality infection control. PMID- 7772977 TI - Infection control and the bedside nurse. AB - Safe infection control practice implies that caregivers have an insight into the factors that contribute to hospital-acquired infections which enables them to provide informed care and examine patient treatment outcomes. However, results of recent studies suggest that this is far from the case. This article examines why this area of nursing knowledge and practice has remained unquestioned and urges for an examination of how nurses are prepared for safe, informed infection control practice. PMID- 7772978 TI - Breast cancer treatment. AB - This article reviews the developments in the management and prognosis of women with early breast cancer. Early diagnosis and the relevant therapies are examined and the value of good communication with breast cancer patients is explored. PMID- 7772979 TI - Nurse management of corneal abrasion. AB - Corneal abrasion is a commonly occurring eye injury accounting for approximately 12.5% of clients seen in the Nottingham eye casualty department. This article describes the anatomy of the cornea and outlines the nurse management and treatment of traumatic corneal abrasion within a clinical setting. PMID- 7772980 TI - The role of learning disability nurses. PMID- 7772982 TI - Self-advocacy in learning disabilities. AB - This article examines the complexities of helping people with a learning disability to develop self-advocacy skills and accordingly proposes that self advocacy should take an explicit place in the RNMH curriculum. PMID- 7772983 TI - The experience of advocacy. 2: A group member's perspective. AB - This article examines advocacy and is written from a client's perspective. Hilary Drage is an experienced self-advocate and founder member of the Banbury Advocacy Group for Adults with a Learning Disability. Here she gives a personal account of the practice of self-advocacy and the functioning of a self-advocacy group. The article is based on an interview with Steve McNally. PMID- 7772981 TI - Empowering consumers: the caring challenge. AB - This article considers current issues relating to power relationships that exist between learning disability nurses and their clients. It examines the changing role of learning disability nurses and considers their influence on enhancing the quality of life for people with learning disabilities, whose autonomy and right to decision making has been consistently challenged throughout society. PMID- 7772984 TI - Staff stress and satisfaction in small staffed houses in the community: 1. AB - In this article, the first of two parts, the sources of stress and satisfaction experienced by nursing and social service staff working in group homes with young people with severe learning disabilities are investigated. It focuses on the stresses and satisfactions arising out of the performance of the direct care role for staff working in ordinary housing in the community. PMID- 7772985 TI - Should nurses be politically aware? AB - In the present atmosphere of change, nurses need to develop political awareness. This article reviews the many factors that have mitigated against such a development and examines how these have adversely affected the profession. It proposes that nurses must develop political awareness as only by becoming politically knowledgeable can they can control and shape their own destiny, and effectively contribute to the decisions that affect their patients. PMID- 7772986 TI - Protecting patient confidentiality. PMID- 7772988 TI - Reliability: consistency and accuracy in measurement. PMID- 7772987 TI - Advantages of primary nursing in geriatric day hospitals. AB - This article presents a rationale for the introduction of primary nursing as the most suitable method of organisation in geriatric day hospitals. Working conditions, the status of the nurse within the multidisciplinary team and the opportunities afforded by primary nursing for enhancing the nurse-patient relationship are examined. PMID- 7772989 TI - Law series: 7. Extended role of the nurse. PMID- 7772990 TI - Integrating nursing research and practice: Part I--A journey into the unknown. AB - We must all face the challenge of weaving together the art and science of nursing, of integrating nursing research and practice. In a two part article Northland nurses tell about their experiences with research and the study they carried out. Part one describes their beginning experiences with integrating research and practice. PMID- 7772991 TI - The diagnosis of schizophrenia and its impact on the primary caregiver. AB - This qualitative study investigates how the diagnosis of schizophrenia in a young adult impacts on the primary caregiver in the family. In this study all participants were mothers who had sons recently diagnosed with schizophrenia. An extensive literature review revealed a lack of research in this area. The research methodology is described. Data analysis determined themes or patterns of experience amongst participants in this study. From this small study it was seen that the impact on the participants was intensely traumatic and far reaching. Six themes emerged: trauma/distress, fear, uncertainty, relief, disruption and powerlessness. The results have major implications for nurses and other health professionals working in the Mental Health field. PMID- 7772992 TI - The knowing and doing of empowerment. PMID- 7772993 TI - Valuing students' experience in nursing education. PMID- 7772994 TI - The adventures of nursing practice through research. Report of International Nursing Research conference: Sydney Australia, July 1994. PMID- 7772995 TI - Advocacy in action. PMID- 7772996 TI - Did I do right? PMID- 7772997 TI - Care: a superior ideal for nursing? PMID- 7772998 TI - Neuromuscular development in Drosophila: insights from embryos and pupae. AB - During embryogenesis, Drosophila melanogaster generates a set of muscles and motoneurons that are restructured during pupal metamorphosis to give rise to an adult motor system. The study of neuromuscular development in embryos and pupae has recently revealed important insights into the cellular and molecular mechanisms controlling both muscle patterning and the establishment of synaptic connections. PMID- 7772999 TI - Activity-dependent remodeling of connections in the mammalian visual system. AB - The development of precise connections in the mammalian central nervous system requires neural activity. Synchronous patterns of afferent activity, and coincident afferent and target activity are required for specifying the neuronal connectivity that characterizes the adult visual pathway in mammals. During development, postsynaptic target neurons communicate with presynaptic afferents. Recent evidence suggests that the mechanisms that underlie activity-dependent development of connections in the visual system may share significant similarities with the mechanisms responsible for synaptic plasticity in the adult brain. PMID- 7773000 TI - Development. PMID- 7773001 TI - Intrinsic and extrinsic factors regulating vertebrate neurogenesis. AB - Recent studies of the factors regulating neurogenesis in vertebrates reveal three emerging themes. First, the number of cellular stages involved in this process may be greater than has previously been appreciated. Second, homologues of genes that regulate neurogenesis in invertebrates appear to play analogous roles in development of vertebrate nervous systems. Third, extrinsic factors can act to regulate neuron number during neurogenesis by controlling survival and differentiation, and not simply proliferation, of neural progenitor cells. PMID- 7773003 TI - Molecular genetics of neuronal adhesion. AB - Cell-cell and cell-matrix interactions are believed to play crucial roles in neural development. Cell adhesion molecules of the immunoglobulin and cadherin families, as well as integrin heterodimers and extracellular matrix glycoproteins, are widely expressed in the nervous system. The advent of gene targeting technology has heralded a new era for study of their function. Initial observations in 'knockout' mice have yielded some surprising results. PMID- 7773002 TI - Remodeling of the insect nervous system. AB - Our nervous systems and behavior are shaped by hormonally driven developmental changes that continue beyond the embryonic period. Key insights into this process have emerged from studies of the insect nervous system. During insect metamorphosis, the nervous system is remodeled through postembryonic neurogenesis, programmed cell death and the modification of persistent neurons. These changes are regulated to a large degree by gene cascades that are triggered by steroid hormones, the ecdysteroids. Current studies are attempting to reveal the molecular mechanisms involved in regulating these dramatic examples of developmental plasticity. PMID- 7773005 TI - Development of the zebrafish nervous system: genetic analysis and manipulation. AB - The accessibility and simplicity of the zebrafish embryo have led to fruitful examinations of how vertebrate embryos develop, at the cellular level. Recently, several groups have initiated large-scale mutagenesis in zebrafish and begun to generate transgenic zebrafish. The goals of these endeavors are to identify developmentally important genes and to delineate their in vivo function. If successful, the two approaches should significantly enhance our understanding of how genes control development in a vertebrate embryo. PMID- 7773004 TI - Molecular genetics of neuronal survival. AB - The past year has witnessed remarkable progress towards understanding the molecular genetics of neuronal survival. Gene-targeting experiments in mice have confirmed the long-standing idea that the nerve growth factor model of neuronal survival--that is, neuronal dependence on target-derived molecules during a critical period in development--is broadly applicable. Furthermore, a variety of biochemical and genetic techniques applied to both mammals and invertebrates have identified new genes involved in regulating cell survival during development. PMID- 7773006 TI - Targeting of mRNAs to subsynaptic microdomains in dendrites. AB - Recent studies have revealed that a heterogeneous population of mRNAs is present in neuronal dendrites (including mRNAs that encode proteins involved in intracellular signaling), that different types of neurons have different assortments of dendritic mRNAs, and that the levels of some dendritic mRNAs are up-regulated by activity. These findings reinforce and extend the hypothesis that the localization of mRNA in dendrites provides a means of synthesizing proteins locally that are important for synaptic function. PMID- 7773007 TI - Control of neuronal development in Caenorhabditis elegans. AB - Recent research into the development of the nervous system of the nematode Caenorhabditis elegans indicates the importance of multiple cell interactions and combinatorial gene expression. As many of the genes needed for C. elegans neuronal development have counterparts with similar activities in Drosophila melanogaster, the mechanisms of cell specification may be broadly conserved. PMID- 7773008 TI - Assembly of the postsynaptic apparatus. AB - Recent research has led to a clearer picture of the molecular organization of the postsynaptic apparatus at the developing neuromuscular junction. In addition, one link between the extracellular signaling molecule agrin and the intracellular events that mediate formation of acetylcholine receptor clusters has been established with the identification of an argin-binding protein. PMID- 7773010 TI - Guidance and induction of branch formation in developing axons by target-derived diffusible factors. AB - Developing axons appear to navigate to their targets partly in response to long range diffusible chemoattractants secreted by target cells. The past year has seen the identification of the first target-derived attractants for developing axons, the netrins. Target-derived diffusible factors have also been implicated in controlling the elaboration of axon collateral branches, and a recent study provides insight into the mechanism by which this is achieved. Evidence has also suggested neurotrophins and neurotransmitters as candidate branching and chemotropic factors. PMID- 7773009 TI - The sensory-motor role of growth cone filopodia. AB - Neuronal growth cones, the motile tips of elongating axons and dendrites, respond very precisely to cues encountered during pathfinding. During the past year, our knowledge about their sensory function, their integrative properties, and their motor function has advanced significantly. In particular, growth cone filopodia are currently being recognized for their prominent roles as sensors, transducers, and autonomous motor structures important for growth cone steering. PMID- 7773011 TI - Development of layers, maps and modules. AB - Developing neuronal cell sheets acquire position-specific features by mechanisms that differ in radial and tangential dimensions. These features include guiding cues for axonal growth and targeting that are used, for example, in map formation. Recent evidence supports the notion that graded distributions of molecules are involved in growth cone navigation and axonal branching. In addition, activity-dependent processes are important determinants of functional architecture, especially with respect to modular organization. PMID- 7773012 TI - Neuronal coupling and uncoupling in the developing nervous system. AB - Sensitive new tracers and imaging techniques have revealed that gap junction coupling during brain development is much more pronounced than previously believed. Recent results demonstrate that cell coupling can produce functional neuron assemblies characterized by synchronized fluctuations in the cytosolic Ca2+ concentration. Coupling is especially pronounced before and during the period of synapse formation and initial establishment of neuronal circuits. Thus, communication via gap junctions may generate coordinated electrical or biochemical activity before the onset of synaptic transmission, and thereby provide the outlines of functional architecture in the developing brain. PMID- 7773013 TI - The APETALA2 domain is related to a novel type of DNA binding domain. PMID- 7773014 TI - The tobacco homolog of mammalian calreticulin is present in protein complexes in vivo. AB - The analysis of protein sorting signals responsible for the retention of reticuloplasmins (RPLs), a group of soluble proteins that reside in the lumen of the endoplasmic reticulum (ER), has revealed a structural similarity between mammalian and plant ER retention signals. We present evidence that the corresponding epitope is conserved in a vast family of soluble ER resident proteins. Microsequences of RPL60 and RPL90, two abundant members of this family, show high sequence similarity with mammalian calreticulin and endoplasmin. RPL60/calreticulin cofractionates and costains with the lumenal binding protein (BiP). Both proteins were detected in the nuclear envelope and the ER, and in mitotic cells in association with the spindle apparatus and the phragmoplast. Immunoprecipitation of proteins from in vivo-labeled cells demonstrated that RPL60/calreticulin is associated with other polypeptides in a stress- and ATP dependent fashion. RPL60/calreticulin transcript levels increased rapidly in abundance during the proliferation of the secretory apparatus and the onset of hydrolase secretion in gibberellic acid-treated barley aleurone cells. This induction profile is identical to that of the well-characterized ER chaperones BiP and endoplasmin. However, expression patterns in response to different stress conditions as well as tissue-specific expression patterns indicate that these genes are differentially regulated and may not act in concert. PMID- 7773015 TI - The brown midrib3 (bm3) mutation in maize occurs in the gene encoding caffeic acid O-methyltransferase. AB - The brown midrib mutations are among the earliest described in maize. Plants containing a brown midrib mutation exhibit a reddish brown pigmentation of the leaf midrib starting when there are four to six leaves. These mutations are known to alter lignin composition and digestibility of plants and therefore constitute prime candidates in the breeding of silage maize. Here, we show that two independent brown midrib3 (bm3) mutations have resulted from structural changes in the COMT gene, which encodes the enzyme O-methyltransferase (COMT; EC 2.1.1.6), involved in lignin biosynthesis. Our results indicate that the bm3-1 allele (the reference mutant allele) has arisen from an insertional event producing a COMT mRNA altered in both size and amount. By sequencing a COMT cDNA clone obtained from bm3-1 maize, a retrotransposon with homology to the B5 element has been found to be inserted near the junction of the 3' coding region of the COMT gene intron. The second bm3 allele, bm3-2, has resulted from a deletion of part of the COMT gene. These alterations of the COMT gene were confirmed by DNA gel blot and polymerase chain reaction amplification analyses. These results clearly demonstrate that mutations at the COMT gene give a brown midrib3 phenotype. Thus, the gene genetically recognized as bm3 is the same as the one coding for COMT. PMID- 7773016 TI - Characterization of the maize gene sugary1, a determinant of starch composition in kernels. AB - In maize kernels, mutations in the gene sugary1 (su1) result in (1) increased sucrose concentration; (2) decreased concentration of amylopectin, the branched component of starch; and (3) accumulation of the highly branched glucopolysaccharide phytoglycogen. To investigate further the mechanisms of storage carbohydrate synthesis in maize, part of the su1 gene locus and a cDNA copy of the su1 transcript were characterized. Five new su1 mutations were isolated in a Mutator background, and the mutant allele su1-R4582::Mu1 was isolated by transposon tagging. The identity of the cloned element as the su1 gene locus was confirmed by the cosegregation of restriction fragment length polymorphisms in the same or nearby genomic intervals with three additional, independent su1 mutations. Pedigree analysis was also used to confirm the identity of su1. A 2.8-kb mRNA that is homologous to the cloned gene was detected in maize kernels, and a 2.7-kb cDNA clone was isolated based on hybridization to the genomic DNA. Specific portions of the cDNA hybridized with multiple segments of the maize genome, suggesting that su1 is part of a multigene family. The cDNA sequence specified a polypeptide of at least 742 amino acids, which is highly similar in amino acid sequence to bacterial enzymes that hydrolyze alpha-(1-->6) glucosyl linkages of starch. Therefore, debranching of glucopolysaccharides is seemingly part of the normal process of starch biosynthesis, and the final degree of branch linkages in starch most likely arises from the combined actions of branching and debranching enzymes. PMID- 7773017 TI - Arabidopsis phosphoribosylanthranilate isomerase: molecular genetic analysis of triplicate tryptophan pathway genes. AB - Phosphoribosylanthranilate isomerase (PAI) catalyzes the third step of the tryptophan biosynthetic pathway. Arabidopsis PAI cDNAs were cloned from a cDNA expression library by complementation of an Escherichia coli trpC- PAI deficiency mutation. Genomic DNA blot hybridization analysis detected three nonallelic genes encoding PAI in the Arabidopsis genome. DNA sequence analysis of cDNA and genomic clones indicated that the PAI1 and PAI2. All three PAI polypeptides possess an N terminal putative plastid target sequence, suggesting that these enzymes all function in plastids. The PAI1 gene is flanked by nearly identical direct repeats of approximately 350 nucleotides. Our results indicate that, in contrast to most microorganisms, the Arabidopsis PAI protein is not fused with indole-3 glycerolphosphate synthase, which catalyzes the next step in the pathway. Yeast artificial chromosome hybridization studies indicated that the PAI2 gene is tightly linked to the anthranilate synthase alpha subunit 1 (ASA1) gene on chromosome 5. PAI1 was mapped to the top of chromosome 1 using recombinant inbred lines, and PAI3 is loosely linked to PAI1. cDNA restriction mapping and sequencing and RNA gel blot hybridization analysis indicated that all three genes are transcribed in wild-type plants. The expression of antisense PAI1 RNA significantly reduced the immunologically observable PAI protein and enzyme activity in transgenic plants. The plants expressing antisense RNA also showed two phenotypes consistent with a block early in the pathway: blue fluorescence under UV light and resistance to the anthranilate analog 6-methylanthranilate. The extreme nucleotide conservation between the unlinked PAI1 and PAI2 loci suggests that this gene family is actively evolving. PMID- 7773018 TI - Inhibition of the glycine decarboxylase multienzyme complex by the host-selective toxin victorin. AB - Victoria blight of oats is caused by the fungus Cochliobolus victoriae. This fungus is pathogenic due to its ability to produce the host-selective toxin victorin. We previously identified a 100-kD protein that binds victorin in vivo only in susceptible genotypes and a 15-kD protein that binds victorin in vivo in both susceptible and resistant genotypes. Recently, we determined that the oat 100-kD victorin binding protein is the P protein of the glycine decarboxylase complex (GDC). In this study, we examined the effect of victorin on glycine decarboxylase activity (GDA). Victorin was a potent in vivo inhibitor of GDA. Leaf slices pretreated for 2 hr with victorin displayed an effective concentration for 50% inhibition (EC50) of 81 pM for GDA. Victorin inhibited the glycine-bicarbonate exchange reaction in vitro with an EC50 of 23 microM. We also identified a 15-kD mitochondrial protein that bound victorin in a ligand-specific manner. Based on amino acid sequence analysis, we concluded that the 15-kD mitochondrial protein is the H protein component of the GDC. Thus, victorin specifically binds to two components of the GDC. GDA in resistant tissue treated with 100 micrograms/mL victorin for 5 hr was inhibited 26%, presumably as a consequence of the interaction of victorin with the H protein. Victorin had no detectable effect on GDA in isolated mitochondria, apparently due to the inability of isolated mitochondria to import victorin. These results suggest that the interaction of victorin with the GDC is central to victorin's mode of action. PMID- 7773020 TI - Caring for the dying in Canada. PMID- 7773019 TI - Mutations in the NPH1 locus of Arabidopsis disrupt the perception of phototropic stimuli. AB - The phototropic response is an important component of seedling establishment in higher plants because it orients the young seedlings for maximal photosynthetic light capture. Despite their obvious importance, little is known about the mechanisms underlying the perception and transduction of the light signals that induce phototropic curvatures. Here, we report the isolation of eight mutants of Arabidopsis that lack or have severely impaired phototropic responses. These nph (for nonphototropic hypocotyl) mutants comprise four genetic loci: nph1, nph2, nph3, and nph4. Physiological and biochemical characterization of the nph1 allele series indicated that the NPH1 locus may encode the apoprotein for a dual chromophoric or multichromophoric holoprotein photoreceptor capable of absorbing UV-A, blue, and green light and that this photoreceptor regulates all the phototropic responses of Arabidopsis. It appears that the NPH1 protein is most likely a 120-kD plasma membrane-associated phosphoprotein because all of the nph1 mutations negatively affected the abundance of this protein. In addition, the putative NPH1 photoreceptor protein is genetically and biochemically distinct from the HY4 protein, which most likely acts as a photoreceptor for blue light mediated hypocotyl growth inhibition. Furthermore, the NPH1 and HY4 proteins are not functionally redundant because mutations in either gene alone affect only one physiological response but not the other, thus providing strong support for the hypothesis that more than one blue light photoreceptor is required for the normal growth and development of a seedling. PMID- 7773021 TI - Specifics needed on safe dosage. PMID- 7773022 TI - Earlier postdischarge visits promote breastfeeding. PMID- 7773023 TI - Medical care of the dying. Where do family physicians fit in? PMID- 7773024 TI - Family physician hospital privileges. New approach. PMID- 7773025 TI - Dilemmas in care of the elderly. PMID- 7773026 TI - Do widowers use the health care system differently? Does intervention make a difference? AB - OBJECTIVE: To describe the health care use patterns of widowers who had participated in a randomized trial of mutual support, and of a matched cohort of married men DESIGN: Retrospective audit of Ministry of Health use data SETTING: The family practice unit in a general teaching hospital. PARTICIPANTS: The 113 new widowers (61 treatment, 52 waiting-list controls) who participated in a randomized trial of mutual support, and 111 married men matched for age INTERVENTIONS: Mutual support program MAIN OUTCOME MEASURES: Monthly rates of visits to family physicians, psychiatrists, and all other specialists for the three cohorts RESULTS: Visit rates to family physicians and specialists (SPs) for the married men were stable for the 20 months of the study; rates for the widowers rose significantly from the time of loss to the end of the intervention (for FPs, f = 13.18, df = 2, P < .01; for SPs, f = 5.34, df = 2, P = .005). Rates for FPs declined after intervention for the treatment group, but kept rising among the controls (f = 4.17, df = 1, P = .044). CONCLUSIONS: The decreased physician visit rate among those taking part in the mutual support program suggests that this program met some of the widowers' social support needs that would otherwise have led to the use of health care resources. PMID- 7773027 TI - [Preliminary validation of instruments used to measure the psychotherapeutic knowledge, skills and attitudes of family physicians]. AB - OBJECTIVE: To examine the validity and the reliability of three measurement instruments used to evaluate mental health training offered to residents in family medicine. DESIGN: Development and submission of three French-language instruments measuring knowledge, perceived skills, and attitudes of family physicians and residents. SETTING: Weekly psychotherapy workshop. PARTICIPANTS: A group of 90 family medicine residents and practising doctors were recruited by the authors and by teaching facilities. MAIN OUTCOME MEASURE: Reliability index KR20 and an evaluation of error in the instruments were used. RESULTS: The results satisfactory in terms of the measurement of perceived skills (KR20 = 0.86) and the measurement of attitudes (KR20 = 0.96); the measurement of knowledge (KR20 = 0.70) was clearly unsatisfactory and the instrument will require upgrading. The measurement of perceived skills was the only one to reveal a distinction between the groups; practising doctors and those interested in psychotherapy believed their skills to be superior to those of residents in training (P = 0.005). CONCLUSION: Instruments measuring attitudes and perceived skills have excellent psychometric potential; however, it remains to be determined whether the measurement of perceived skills is valid and whether these instruments are useful for monitoring family medicine residents during their training or for assessing the impact of mental health training programs. PMID- 7773028 TI - [Hypercalcemia in cancer patients. Who, when and how to treat?]. AB - The most frequent, potentially fatal, metabolic complication in cancer patients is hypercalcemia. After a discussion of cancer-associated hypercalcemia, we propose an individualized intervention model based on an analysis of the clinical situation, the prognosis, and available treatment options. PMID- 7773029 TI - Evaluating tall children. AB - The causes of tall stature are numerous; genetic tall stature and constitutional tall stature are the most common. Diagnosis can usually be established from the history and physical examination. An estimation of bone age can help to confirm diagnosis and to determine the child's growth potential. No treatment is usually necessary. Hormonal therapy can be considered for individuals for whom the predicted height is excessive if the psychosocial and medical advantages outweigh the risks of treatment. PMID- 7773030 TI - The rights of patients in research. PMID- 7773031 TI - Comparing treatments. PMID- 7773032 TI - Lower patients' cholesterol now. PMID- 7773033 TI - The importance of clinical skills. PMID- 7773034 TI - Diagnosing and managing occupational disease. PMID- 7773035 TI - Canada's health care system faces criticism. PMID- 7773036 TI - French to get hospital for Chinese medicine. PMID- 7773037 TI - Australian health insurance reforms face collapse. PMID- 7773039 TI - Barriers to health care in the single market. PMID- 7773038 TI - Survey highlights risk of foreign holidays. PMID- 7773040 TI - Contribution of dihydrotestosterone to male sexual behaviour. AB - OBJECTIVE: To document the relative importance of endogenous sex steroids in modulating the frequency of orgasms, the dominant aspect of sexual behaviour in healthy eugonadal men. DESIGN: Measurement of adrenal and testicular sex steroids in a sample of army recruits and study of their relation to frequency of orgasms ascertained by questionnaire after potential confounding variables were controlled for. SETTING: Military campus and military hospital laboratories in Athens, Greece. SUBJECTS: 92 consecutively enrolled healthy male recruits aged 18 22 years. MAIN OUTCOME MEASURES: Weekly number of orgasms. Serum concentrations of testosterone, dehydroepiandrosterone sulphate, dihydrotestosterone, oestradiol, oestrone, delta-4-androstenedione, and sex hormone binding globulin. RESULTS: Serum dihydrotestosterone concentration was the only independent hormonal predictor of the frequency of orgasms; an increase in concentration of 1.36 nmol/l (about 2 SD) corresponded to an average increase of one orgasm a week. CONCLUSIONS: Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men. PMID- 7773041 TI - Prevalence of knee problems in the population aged 55 years and over: identifying the need for knee arthroplasty. AB - OBJECTIVE: To determine the prevalence of knee problems in people aged 55 years and over and identify those who should be considered for knee arthroplasty. DESIGN: Postal survey; questionnaires were sent to a multistage stratified probability sample of residents of North Yorkshire Health Authority aged 55 and over. SETTING: A health district with a population of 210,000 aged 55 and over. RESULTS: An initial four page postal questionnaire produced an 86% response rate among 18,827 eligible patients. A subsequent detailed questionnaire sent to 1277 patients with knee problems (with a response rate of 78%) then determined the prevalence of severe pain and severe disability. Pain and disability consistent with the need to consider arthroplasty was found in 20.4/1000 (95% confidence interval 18.0 to 23.1); of these, 4.1 (2.7 to 5.8)/1000 had extreme disability. Age and sex specific rates in men who might benefit from arthroplasty were, in those aged 55-64, 12.9 (8.4 to 19.0)/1000; aged 65-74, 12.1 (7.4 to 18.4)/1000; aged 75 and over, 20.3 (12.9 to 30.5)/1000. In women aged 55-64 the rates were 12.9 (8.6 to 18.7)/1000; aged 65-74, 19.6 (13.9 to 26.7)/1000; aged 75 years and over, 42.6 (34.3 to 52.4)/1000. CONCLUSIONS: Total knee replacement has until recently been considered unreliable and often seen as a last resort for many with severe knee problems. Advances in prosthesis design and surgical and anaesthetic techniques have transformed this procedure into a reliable option with a potential for reducing disability and dependency in a large number of people in the community. Understandably, the prevalence pool of those who may benefit is large; health authorities and, increasingly, general practitioners should consider purchasing more total knee replacement surgery to offer real choice to those in need. PMID- 7773043 TI - General practitioners' knowledge of notifiable, reportable, and prescribed diseases. PMID- 7773042 TI - Ten year cerebrovascular morbidity and mortality in 68 year old men with asymptomatic carotid stenosis. AB - OBJECTIVE: To study the natural course of carotid artery stenosis detected by ultrasonography. DESIGN: Prospective cohort study. Baseline examination in 1982-3 included ultrasound examination of carotid arteries, measurement of ankle brachial blood pressure index, and detection of atrial fibrillation by 24 hour ambulatory electrocardiography. SETTING: Malmo, a city in southern Sweden with 230,000 inhabitants. SUBJECTS: 470 men aged 68 years randomly selected from the population. MAIN OUTCOME MEASURES: Incidence of stroke and transient ischaemic attack and all cause mortality during 10 years of follow up in relation to carotid stenosis, leg artery disease (ankle-brachial blood pressure index below 0.9), and atrial fibrillation. RESULTS: Fifty men had a stroke; six of these were haemorrhagic. Another 11 had a transient ischaemic attack. Eighteen of the men with carotid stenosis (21.6 events/1000 person years) and 43 of the men with normal carotid arteries (14.8 events/1000 person years) had a stroke or transient ischaemic attack (P = 0.188). Men with atrial fibrillation had an increased rate of cerebrovascular events (36.7/1000 person years (P = 0.048). The highest rate was found in men with asymptomatic disease of the leg arteries (38.6/1000 person years) (P < 0.001). The increased risk of stroke or transient ischaemic attack in this group remained after multivariate analysis (relative risk 2.0; 95% confidence interval 1.1 to 3.7). CONCLUSIONS: In this cohort carotid stenosis was not associated with an increased risk of stroke. Part of this lack of association was explained by the high mortality from ischaemic heart disease in men with severe stenosis. Twenty seven of the 61 cerebrovascular events, however, occurred in men who had normal carotid arteries, normal ankle pressure, and no atrial fibrillation. PMID- 7773044 TI - Industrial injury benefit for occupational asthma in north east of England. PMID- 7773045 TI - GPs in principle but not in practice: a study of vocationally trained doctors not currently working as principals. AB - OBJECTIVES: To identify doctors who are vocationally trained but not currently practising as principals in general practice; their reasons for not practising as principals; and whether the prospect of a re-entry course would appear to this group. DESIGN: Postal questionnaire survey based on semistructured interviews. SUBJECTS: Doctors who had been vocationally trained but were not currently practising as principals: 351 possible subjects identified by a process of "networking." SETTING: Trent Regional Health Authority. RESULTS: 166 of the doctors who replied fitted the criteria (100 women; 66 men). The out of hours commitment was ranked as the most important factor for not practising as a principal--95 women and 50 men rated it important--followed by difficulty in combining work with family commitments--84 women, 31 men. 82 respondents (49%) said they would be interested in a re-entry course if one were available. CONCLUSIONS: There is a pool of vocationally trained doctors in Trent region who are not practising as principals in general practice. More flexible working patterns and the availability of a re-entry course could make the post of principal in general practice a more attractive proposition to these doctors. PMID- 7773046 TI - Registration of drugs for treating cancer and HIV infection: a plea to carry out phase 3 trials before admission to the market. AB - Drugs for cancer and HIV infection tend to be admitted to the market on the basis of results from phase 2 trials. Assessing the benefit-risk balance with phase 2 trials often is difficult--the effect of the drug is usually temporary; the correlation between response or improvement of clinical measurements and the patient's wellbeing is often poor; and the side effects of drugs for these fatal diseases are serious. Therefore, although sometimes difficult to conduct, comparative trials that use standard treatment, placebos, or best supportive care remain the cornerstone for reliably assessing the benefit-risk balance. PMID- 7773047 TI - New South Africa's doctors: a state of flux. PMID- 7773048 TI - China takes to the roads. AB - China is undergoing rapid motorisation--motor vehicle registrations are growing at a rate of 10%-20% a year. Road trauma is already a major public health problem, and road deaths, officially estimated to be around 50,000 a year, will almost certainly rise with increasing motorisation. China, with its millions of bicycles, currently has one of the most environmentally friendly transportation systems on the planet. However, as the trend towards car travel continues, the problems of congestion and environmental pollution so evident in the West will also become critical public health issues in China. PMID- 7773049 TI - Publication: an ethical imperative. AB - Publication of medical research is both a monitor of the researcher's ethics and an audit of the local or regional ethics committee that approved it. Selectivity of publication or of the intention to publish lessens this audit. Opinions differ about what is ethically allowable in clinical and benchtop medical research. Ethical permission and ethical monitoring of medical research are subject to a hierarchy of pyramidal controls, starting in hospital and ending with the local, institutional, or regional ethics committee. Currently, such committees function with widely varying degrees of efficiency and quality of output, and with differing viewpoints on many ethical issues. Without an a priori insistence by institutional ethics committees that there be an intention to publish all medical research involving human subjects, ethics committees cannot routinely be subject to the scrutiny or audit which they themselves demand of researchers. PMID- 7773050 TI - What do I want from health research and researchers when I am a patient? AB - I have attempted to adopt the perspective of a patient--albeit one with a rather atypical background--to explore what I want from health research and researchers. This has left me with the impression that health researchers could serve the interests of the public more effectively in a variety of ways, and that they would be helped to do so by greater lay involvement in planning and promoting health research. PMID- 7773051 TI - How can health service users contribute to the NHS research and development programme? AB - The National Childbirth Trust, along with other groups of health service users, is working with health professionals and researchers in planning clinical trials, setting priorities for research, systematically reviewing research reports, and getting research findings into practice. User groups may bridge the gap between the public and researchers by explaining research issues to a wide audience, presenting the needs and views of health service users to the research community, and suggesting how members of the public may be approached for their views directly. Service users recognise their need for training and support, and they call for development and evaluation of this work. PMID- 7773052 TI - ABC of rheumatology. Spondyloarthropathies. PMID- 7773053 TI - Accuracy of local data on skin cancer. Skin cancer registry data may greatly underestimate cases. PMID- 7773054 TI - People are overusing sunbeds. PMID- 7773055 TI - Accuracy of local data on skin cancer. Inaccurate data may lead to insufficient resources. PMID- 7773056 TI - Accuracy of local data on skin cancer. Computerised data collection systems have not improved data collection. PMID- 7773057 TI - Chemotherapy for solid tumours. PMID- 7773058 TI - Profiting from the NHS. PMID- 7773059 TI - Prophylaxis against malaria. PMID- 7773060 TI - Community psychiatric nurses and drug regimens. PMID- 7773061 TI - Cot death among Maori. PMID- 7773062 TI - GPs' attitudes to a self diagnosis of myalgic encephalomyelitis. Evidence supports presence of encephalitis. PMID- 7773063 TI - Mortality among twins. PMID- 7773064 TI - Temperature and cardiovascular mortality. PMID- 7773065 TI - Undernotification of whooping cough. PMID- 7773066 TI - Management of severe gastroparesis diabeticorum. PMID- 7773067 TI - Exercise and diverticular disease. PMID- 7773068 TI - Fitness programme for chronic low back pain. Details of the exercises are not given. PMID- 7773069 TI - Biological influences on criminal behaviour. PMID- 7773070 TI - Albumin in the nephrotic syndrome. PMID- 7773072 TI - Advance directives. PMID- 7773071 TI - Sedation in fibreoptic bronchoscopy. PMID- 7773074 TI - Measles campaign. PMID- 7773073 TI - Injury to child pedestrians. PMID- 7773075 TI - The Gulf War syndrome. PMID- 7773076 TI - Future of intensive care. PMID- 7773077 TI - Transferring the costs of expensive treatments. Guidelines may clarify responsibility for prescribing. PMID- 7773078 TI - [Acute drug poisonings]. PMID- 7773079 TI - [The interaction of dopamine and opioid receptors in the re-establishing of an amnesic and forgotten memory trace by quinpirole]. AB - The present study evaluated the contribution of delta and kappa opioid receptors to the dopamine-mediated reestablishment of an amnestic and forgotten memory trace. Using passive avoidance as a memory index, the pretraining injection of leukephalin was determined to enhance the efficiency of quinpirole, a selective dopamine D-2 receptor agonist, to reactivate the memory retrieval in amnesia and forgetfulness. In contrast, pretreatment with dynorphin attenuated the retrieval by enhancing the effect of the pretesting injection of quinpirole in amnesia. Quinpirole was found to be more effective in attenuating amnesia than forgetfulness. PMID- 7773080 TI - [The comparative characteristics of the spectrum of the pharmacological action of azaleptin and GCh-46]. AB - Experiments on mice and rats were made to make a comparative evaluation of the psychotropic properties of asaleptin (leponex) and GCh-46. There were significant differences between the agents. Asaleptin, as a typical neuroleptic, had no anticonvulsant activity. But preserving some properties of asaleptin, GCh-46 produced pronounced anticonvulsant effects comparable with those shown by traditional antiepileptic agents. PMID- 7773081 TI - [The genetic characteristics of the brain alpha 2-adrenergic and S2 serotoninergic systems in the realization of the tail-jerk pain reflex and its morphine suppression in rats]. AB - Experiments were conducted on two inbred rat strains--WAG/G and Fischer-344. The WAG/G rats were found to increase the density of brain cortical mu-opiate and alpha 2-adrenergic receptors, short latency of tail immersion from hot water, decreased analgesic action of 5 mg/kg of intraperitoneal morphine and pronounced analgesic action of 10 micrograms of intracerebral ventricular clonidine The Fischer-344 rats increased S2-receptor affinity, protracted pain latency, increased the analgesic action of morphine (5 mg/kg i.p.), serotonin (0.5 microgram i.c.v.), and ketanserine (1 microgram i.c.v.). The intracerebral ventricular administration of clonidine, serotonin, yohimbine, and ketaserine significantly increased the analgesic action of morphine in the two strains. It is suggested that a prompt pain response and increased analgesic action of morphine in Fischer-344 rats may be determined by higher affinity of serotoninergic receptors, but a slow pain reflex and decreased morphine-induced analgesia of WAG/G rats may be caused by the high density of brain cortex alpha 2 adrenergic receptors. PMID- 7773082 TI - [Individual sensitivity to the cerebrovascular antiserotonin action of propranolol and tolfenamic acid]. AB - Experimentally, metisergide largely prevents and attenuates the development of cerebrovascular constrictive responses evoked by serotonin. Propranolol and tolphenamic acid alleviate decreases in the volumetric velocity of brain blood flow, which are induced by serotonin in half of the total number of experiments whereas in the other experiments these agents show no antiserotonin cerebrovascular properties. PMID- 7773084 TI - [The effect of antidepressants on the indices of the cardiointervalogram in intact rats and during the deprivation of paradoxical sleep]. AB - The acute and chronic administration of antidepressants (amitriptyline, imipramine, befol) to rats led to the sympathetic influences of a cardiointervalogram as reduced cardiointervals and its increased amplitude and tension index. Imipramine was found to be effective in eliminating disadaptational abnormalities in cardiac performance, which promoted REM-sleep deprivation. PMID- 7773083 TI - [The effect of cerebrocrast on the microcirculation in acute transient cerebral ischemia]. AB - In experiments on rats with cerebral ischemia (30-min occlusion of carotid arteries), the novel calcium antagonist Cerebrocrast (0.4 microgram.kg-1.min-1 i.v. for 15 min) was found to provide the functional maintenance of the parietal cerebral bed in the postischemic period by improving cerebral hemodynamics, reducing the number of highly narrowed capillaries. The agent prevented the erythrocytic accumulation of lipid peroxidation (LPO) products (diene conjugates and Schiff bases) in the intra- and postischemic periods, promoted the maintenance of viscoelastic properties during LPO activation. PMID- 7773085 TI - [The clinical pharmacology of antianginal agents]. AB - This paper provides the basic advances made in studying the clinical pharmacology of antianginal agents (AAs), demonstrates the contribution of current tools for evaluating their antianginal effects, namely pharmacodynamic studies using pair bicycle ergometry and repeated treadmill exercises, 24-hour ECG monitoring, pharmacokinetic studies. It shows that AAs can be chosen on an individual basis. The authors present pharmacodynamic characteristics of a number of new AAs from nitrates (trinitrolong, dinitrosorbilong, etc.), calcium antagonists, beta adrenoblockers (proxodolol, etc.). They have developed a method for assessing the biological equivalence of AAs. The paper discusses the tolerance that can be developed to nitrates and how it can be prevented. It first demonstrates that nifedipine tolerance can develop and that the withdrawal syndrome can occur if nitrates and calcium antagonists are discontinued. There are screening data on various combinations of AAs. A two-stage scheme for choosing an AA therapy is given. PMID- 7773086 TI - [The antihypertensive effect of the new cardioselective prolonged-action beta adrenoblocker bisoprolol compared with propranolol, metoprolol and placebo]. AB - The antihypertensive effect of daily doses of three beta-adrenoblockers (Bisoprolol, 10 mg once a day, propranolol, 80 mg twice a day, and methoprolol, 100 mg twice a day), and placebo was examined in 14 patients with persistent mild and moderate hypertension during a double blind cross-over study by using 24-hour monitoring of blood pressure and its routine measurements. The latter made by a mercury sphygmomanometer indicated that the antihypertensive and negative chronotropic effect of Bisoprolol in a dose of 10 mg remained 24 hours after its administration and it did not significantly differ from that of the two other agents given in the above doses. The application of 24-hour blood pressure monitoring allows a more pronounced antihypertensive effect of bisoprolol to be revealed during 24 hours than that displayed by the two agents. Bisoprolol is an effective and safe antihypertensive agent. PMID- 7773087 TI - [The pharmacokinetics and pharmacodynamics of prophylactic doses of aspirin in pregnant women from a group at risk for placental insufficiency]. AB - The pharmacokinetics and pharmacodynamics of small-dose aspirin (60 mg/day) were studied during the second to the third trimesters in pregnant females at a high risk of placental insufficiency. In the group of pregnant women with uncomplicated pregnancies (n = 16), the aspirin kinetic changes which presented with a lower concentration-time index, higher total clearance and larger distribution volume were associated with the gestational age. Similar changes were revealed in the group of pregnant women (n = 4) with advanced placental insufficiency. The findings suggest that the optimal therapeutical aspirin doses should be chosen by the gestational age rather than by the severity of placental insufficiency. PMID- 7773089 TI - [The effect of succinate combined with cytochrome C on postischemic disorders in the skeletal muscle of the extremities]. AB - A combination of succinic acid and cytochrome c was studied for effects on skeletal muscle carbohydrate metabolism in the extremities of rats with experimental arterial occlusion. The administration of the agents into the ischemic area allowed the stores of glycogen and ATP to be preserved, by lowering the activity of glucose-6-phosphate dehydrogenase and lactate dehydrogenase fraction V in the skeletal muscle of rats with extremity ischemia. The intraperitoneal administration of the agents produced no positive metabolic effect. PMID- 7773088 TI - [The possible glyciram stimulation of bone marrow hematopoiesis under cytostatic blood depression]. AB - The present study was undertaken to examine whether glycyrram orally given can correct blood abnormalities caused by a single maximal tolerable dose of fluorouracil. Glycyrram was demonstrated to stimulate the recovery of granulocytic and erythroid populations of bone marrow hemopoiesis. The stimulating effect of glycyrram was associated with its activating action on the function of hemopoietic microenvironmental cells. PMID- 7773090 TI - [The immunomodulating action of energizing preparations under physical loading]. AB - Riboxin produces a weak actoprotective effect during exercises, while glucose and benfotiamine enhance this effect of the former. Mildronate fails to affect the development of immune response and suppresses the physical fitness in swimming rats. Mildronate in combination with glucose and benfotiamine normalizes their immunological responsiveness and has no effects on the physical fitness. PMID- 7773091 TI - [The effect of Sandimmun on the rate of oxygen consumption by lymphocytes]. AB - Experiments on male Wistar rat thymocytes have demonstrated that cyclosporin A, an active substance of the immunodepressive agent sandimmune given in concentrations of 1 to 10 micrograms/ml, has no effects on cellular oxygen consumption rates measured by the polarographic technique by using a Clarke electrode. At the same time cyclosporin A suppressed thymocyte respiration stimulated by the oxidative phosphorylation release 2,4-DNP (40 micrograms/M) by 18 and 56% when given by concentrations of 2 and 10 micrograms/ml, respectively. The relationship between the adverse effects clinically observed and the findings was also examined. PMID- 7773092 TI - [The effect of antidote preparations on the immune reactions in acute dimethyl dichlorovinyl phosphate poisoning]. AB - Experiments on CBA mice established that acute intoxication with dimethylchlorovinyl phosphate given in a single LD50 of 1.0 increased mice splenic colony-forming cells, decreased thymic T cells, delayed hypersensitivity, natural and antibody-dependent cellular cytotoxicities, sheep splenic red blood cells, thymus-independent Vi antigen antibody production. The antidote therapy with atropine (20 mg/kg) did not stop the main manifestations of posttoxication immunodeficiency and enhanced the suppression of a humoral immune response to sheep red blood cells. Dipyroxim (15 mg/kg) diminished manifestations of postintoxication immunodeficiency. PMID- 7773093 TI - [The effect of reaferon on the opioid systems of chronically alcoholized rats]. AB - Chronic alcoholic intoxication is followed by a fall in 3H-(D-ala-2,D-leu-5) enkephalin affinity of mu-opioid receptors with their unchanged concentrations in the rat brain cortex, by reductions in the tissue and plasma levels of beta endorphine and met-enkephalin. A daily administration of reaferon in a dose of 10,000 IU during two fortnights completely restored both the binding affinity of the receptors and the concentrations of the peptides tested: those of beta endorphine in the adenohypophysis and plasma and those of metenkephalin in the adrenals and plasma. PMID- 7773094 TI - [A multichannel unit for the search for tranquilizers and the study of the mechanisms of their action by the conflict situation method]. AB - This paper outlines an installation for studying the mechanisms of action and searching for new tranquilizers by the conflict situation method. Unlike other such installations, this in question is multichannel, allowing the animals drinking motivation to be concurrently evaluated. PMID- 7773095 TI - [The computerized prediction of the spectrum of biological activity of chemical compounds by their structural formula: the PASS system. Prediction of Activity Spectra for Substance]. PMID- 7773096 TI - [Natriuretic peptides--biologically active substances]. PMID- 7773097 TI - [The pharmacological activity of carnosine]. AB - The properties of the histidine-containing dipeptide carnosine (beta-alanyl-L histidine) and its possible biological role are considered. The agent is discussed in terms of its antioxidative and immunomodulating effects on the body. A history of its discovery and investigations of the therapeutical benefits are outlined. The data given indicate that there are great perspectives in expensively using carnosine as a drug. PMID- 7773100 TI - Isolation of bacteriophage infectious for Vibrio vulnificus. AB - Nine phage isolates infectious for Vibrio vulnificus and falling into four morphological groups were isolated from estuarine waters collected in Louisiana. Of the 60 V. vulnificus strains tested, 87% were susceptible to one or more of the isolates. With the exception of V. fluvialis, Vibrio species other than vulnificus were resistant to infection. A spectrum of enteric bacterial strains were similarly resistant. Susceptibility differences were seen between opaque (virulent) V. vulnificus strains and those with translucent (nonvirulent) colony types, with the former being more susceptible. Susceptibility patterns to infection by the nine phage isolates among the V. vulnificus test strains suggest that the latter may fall into several groups. Other aspects relating to the phage isolates are presented. PMID- 7773099 TI - [Immunomodulators--a new generation of antiviral agents]. PMID- 7773098 TI - [The antianginal action of calcium antagonists: the results of instrumental examination and their clinical assessment]. AB - In 88 patients with coronary heart disease and stable exercise-induced angina pectoris, the efficiency of calcium antagonists was examined by using myocardial Tl-199 scintigraphy and comparing its data with the parameters of angiography and their intracoronary injection. Three types of therapy-induced changes in myocardial perfusion were identified, which were as follows: 1) significant decreases in hypoperfusion area dimensions; 2) no changes in scintigraphic parameters, and 3) clinically asymptomatic increases in the number of hypoperfused sectors. There was a relationship between the therapy-induced changes and the number of sclerotic arteries though the ability of large coronary vessels to dilate was substantially decreased, as shown by angiopharmacological studies. PMID- 7773102 TI - Analysis of a gene region required for dihydrogen oxidation in Azotobacter vinelandii. AB - The putative products of six Azotobacter vinelandii chromosomal open reading frames (ORFs) were suggested to be involved in dihydrogen (H2) metabolism [Chen and Mortenson (1992) Biochim Biophys Acta 1131, 199-202]. A promoterless lacZ containing cassette was used to disrupt the ORFs. Qualitative analysis revealed that the lacZ genes were expressed only in those mutants where the directions of the inserted lacZ were identical to those of the ORFs, showing that the six ORFs were transcribed as predicted. Unlike wildtype (w.t.), none of the mutants could perform dioxygen (O2)-dependent H2-oxidation, even though Western immunoanalyses showed that the hydrogenase large subunit was present although in amounts less than in w.t. Only one of the mutants (a hypB mutant), grown in nickel-enriched media, showed meaningful restoration of the H2-oxidizing ability. From the above observations it is concluded that (a) the six-ORF region is transcriptionally active and involved in H2-oxidation, (b) the product of hypB is needed for nickel activation of hydrogenase, and (c) the six ORFs (genes) belong to two or more operons. Possible roles of the gene products for the assembly, modification, and processing of hydrogenase from its apoproteins and metal centers are discussed. PMID- 7773101 TI - A rapid dot immunoassay for detecting the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius with a "flow through" device. AB - Brazilian purpuric fever (BPF) is a highly fatal pediatric disease that may follow an episode of purulent conjunctivitis caused by a virulent clone of Haemophilus influenzae biogroup aegyptius (Hae). Oral rifampin prophylaxis, by eliminating carriage of the BPF clone in children with conjunctivitis, may prevent onset of the systemic disease. A test to detect the BPF clone directly from eye swabs could identify those in need of prophylaxis. This is a preliminary report of a rapid dot immunoassay performed on a "flow-through" cartridge that was developed for use under field conditions. The test is based upon recognition of a unique epitope of the 25-kDa pilin protein on the surface of BPF clone cells by a monoclonal antibody. With 36 laboratory-maintained cultures of Hae (15 clone isolates and 21 others), sensitivity of the assay was 67% and specificity was 95%. When fimbrial-enriched (25-kDa+) phenotypes of five false-negative clone strains were prepared for use as test antigens, sensitivity rose to 100%. Evaluation of the immunoassay under field conditions is necessary to prove its efficacy. PMID- 7773103 TI - A new alkaline serine protease from alkalophilic Bacillus sp.: cloning, sequencing, and characterization of an intracellular protease. AB - To obtain a new serine protease from alkalophilic Bacillus sp. NKS-21, shotgun cloning was carried out. As a result, a new protease gene was obtained. It encoded an intracellular serine protease (ISP-1) in which there was no signal sequence. The molecular weight was 34,624. The protease showed about 50% homology with those of intracellular serine proteases (ISP-1) from Bacillus subtilis, B. polymyxa, and alkalophilic Bacillus sp. No. 221. The amino acid residues that form the catalytic triad, Ser, His and Asp, were completely conserved in comparison with subtilisins (the extracellular proteases from Bacillus). The cloned intracellular protease was expressed in Escherichia coli, and its purification and characterization were carried out. The enzyme showed stability under alkaline condition at pH 10 and tolerance to surfactants. The cloned ISP-1 digested well nucleoproteins, clupein and salmin, for the substrates. PMID- 7773105 TI - Alcohol in eastern Europe: market prospects, prevention puzzles. PMID- 7773104 TI - Glutamine synthetase/glutamate synthase ammonium-assimilating pathway in Schizosaccharomyces pombe. AB - Kinetic parameters of glutamine synthetase (GS) and glutamate synthase (glutamine oxoglutarate aminotransferase) (GOGAT) activities, including initial velocity, pH, and temperature optima, as well as Km values, were estimated in Schizosaccharomyces pombe crude cell-free extracts. Five glutamine auxotrophic mutants of S. pombe were isolated following MNNG treatment. These were designated gln1-1,2,3,4,5, and their growth could be repaired only by glutamine. Mutants gln1-1,2,3,4,5 were found to lack GS activity, but retained wild-type levels of NADP-glutamate dehydrogenase (GDH), NAD-GDH, and GOGAT. One further glutamine auxotrophic mutant, gln1-6, was isolated and found to lack both GS and GOGAT but retained wild-type levels of NADP-GDH and NAD-GDH activities. Fortuitously, this isolate was found to harbor an unlinked second mutation (designated gog1-1), which resulted in complete loss of GOGAT activity but retained wild-type GS activity. The growth phenotype of mutant gog1-1 (in the absence of the gln1-6 mutation) was found to be indistinguishable from the wild type on various nitrogen sources, including ammonium as a sole nitrogen source. Double-mutant strains containing gog1-1 and gdh1-1 or gdh2-1 (mutations that result specifically in the abolition of NADP-GDH activity) result in a complete lack of growth on ammonium as sole nitrogen source in contrast to gdh or gog mutants alone. PMID- 7773107 TI - Alcohol consumption and all-cause mortality. PMID- 7773106 TI - Alcohol consumption and all-cause mortality. AB - Based on a large US representative cohort with detailed baseline interview and examination data, the relationship between alcohol consumption and all-cause mortality is examined over a period of 15 years follow-up. Results show a significant linear relationship for females and males under 60 years of age at baseline, and a non-significant U-shape for the older ones. Both results remain stable for different kinds of adjustment including adjustment for nutritional variables and smoking. Excluding people with heart disease history at baseline leads to an even more pronounced linear relationship for both males and females under 60 years of age. Furthermore, it is shown that the curvilinear relationship for men found in previous research is partly due to the age groups examined. PMID- 7773108 TI - Analyzing the balance of risk. PMID- 7773109 TI - Moderate drinking and health: being confounded by confounders. PMID- 7773110 TI - The "unhealthy abstainers" question is still important. PMID- 7773111 TI - The J-curve, causality and public health. PMID- 7773112 TI - Means, tails, and the wisdom of Geoffrey Rose. PMID- 7773113 TI - The risk of harm to oneself from drinking, Canada 1989. AB - In a national sample of 11,634 Canadians aged 15 years and above, risk curves for harm to six life-areas from one's own drinking and for assault by another drinker rose steadily with the respondent's volume of alcohol consumption. While drinking five or more drinks on an occasion at least once a month substantially raised the risk at a given volume of drinking, the risk rose with volume even among those not regularly drinking five or more drinks. These relationships remained in logistic regressions which controlled for gender, age and educational level. Younger respondents, those without higher education and men reported more harm for a given level of their own drinking although differences by gender disappeared above one-third of one drink per day. Three sets of guidelines for low-risk drinking--two from Canada, and one generally used in Britain--were compared in terms of the proportions of respondents reporting harm from their own drinking among those who had kept within the guideline in the previous 7 days' drinking. More restrictiveness in the guidelines was associated with substantial reductions in reported drinking-related harm. PMID- 7773114 TI - Prevention strategies and alcohol policy. AB - This paper addresses the potentials of high risk strategy and population strategy for preventing mortality from liver cirrhosis, accidents and suicide. The methodological approach is based on an integration of an empirical distribution of consumption and the risk functions of the damages at issue. According to the findings, the rate of alcohol-induced mortality from the three causes combined would be halved either by a 25 per cent decrease in overall consumption or a 36 per cent decrease in the alcohol consumption of the heavy drinkers (the top 5 per cent). The high risk strategy is most efficient in preventing cirrhosis; however the effect of the population strategy is also quite substantial here. The comparative advantage of the population strategy is most marked in connection with accidents and suicide, but the high risk approach yields an appreciable impact in this context as well. That is, neither of the two strategies appears as clearly superior to the other in terms of efficiency. The high risk strategy thus seems to be a sensible complement to the population strategy, and should have the potential of yielding effects on the population level if implemented on a large scale. PMID- 7773115 TI - The costs of the detrimental effects of alcohol abuse have grown faster than alcohol consumption in Finland. AB - Between 1980 and 1990 alcohol consumption in Finland grew on average by 2.4% per year, and most of the detrimental effects of alcohol abuse grew faster. The real costs from nearly all alcohol-related detrimental effects grew during the 1980s on average by 1.7-2.4% annually, depending on the item. As a result of the volume and cost development the direct detrimental effects of alcohol abuse grew from FIM 1.0-1.3 billion in 1980 to FIM 2.8-3.7 billion in 1990: i.e. a real increase of 51-56% in the direct costs of detrimental effects. The indirect costs of detrimental effects (production losses, value of life lost through premature death), was FIM 9.9-18.1 billion in 1990. In 10 years the distribution of the costs of direct detrimental effects changed markedly, in particular regarding health and social costs: the share of health costs decreased 6 percentage points, while that of social costs increased 10 percentage points. PMID- 7773116 TI - The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption. AB - The Norwegian island of Spitzbergen, Svalbard offers a unique setting for validation studies on self-reported alcohol consumption. No counterfeit production or illegal import exists, thus making complete registration of all sources of alcohol possible. In this study we recorded sales from all agencies selling alcohol on Svalbard over a 2-month period in 1988. During the same period all adults living permanently on Svalbard were invited to take part in a health screening. As part of the screening a self-administered questionnaire on alcohol consumption was introduced to the participants. We found that the self-reported volume accounted for approximately 40 percent of the sales volume. Because of the unique situation applying to Svalbard, the estimate made in this study is believed to be more reliable compared to other studies using sales volume to validate self-reports. PMID- 7773117 TI - HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment. AB - This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT. PMID- 7773118 TI - Administration mode bias in a school survey on alcohol, tobacco and illicit drug use. AB - School surveys have become the most common method for determining the general level of tobacco, alcohol and illicit drug use among adolescents in a large number of countries. The two most commonly applied field procedures in school surveys are teachers' and researchers' administration of questionnaires. The impact of the difference between these two modes of administration has not been determined, although it has been argued that central involvement of teachers in data collection may decrease the perceived anonymity of the survey among students, and should thus be avoided. In a split-half random sample of 3017 urban, Icelandic 16-20-year-old students, no statistically significant differences were found in reported use of licit or illicit drugs, nor in the stated willingness to be honest between these two modes of administration. These results suggest that when students return their responses in sealed envelopes, the two modes of administration produce equally valid results. PMID- 7773119 TI - Parental and peer influences on smoking among young adults: ten-year follow-up of the Oslo youth study participants. AB - This study was designed to investigate the impact of family and peer role models during the early adolescent years on smoking onset and on subsequent daily smoking among young adults. Baseline data were collected from a sample of 827 students and their parents in 1979. Participating students were recruited among 5th, 6th and 7th graders (11-14 years old) attending six schools in Oslo, Norway. The same students were invited to participate in a 2-year follow-up survey in 1981 and in a 10-year follow-up survey in 1989 when their average age was 23.4 years. Both at baseline and in 1981, smoking (experimental or regular) was strongly associated with smoking behaviour of friends and siblings. Parental smoking and parents' educational level were not significant predictors of their offspring's smoking in 1979. While friends' smoking in 1979 or 1981 remained a significant bivariate predictor of daily smoking in 1989, mother's baseline smoking emerged, in multivariate analysis, as the most important long-term predictor of daily smoking among young adults. These results point to the importance of including parents in smoking prevention efforts targeting adolescents. PMID- 7773121 TI - Comments on the European alcohol action plan. PMID- 7773120 TI - Tobacco smoking in young adults from 21 European countries: association with attitudes and risk awareness. AB - Information concerning tobacco smoking was obtained in a survey of 16,483 students aged 18-30 years from 21 European countries. Belief in the benefits to health of not smoking were also assessed. Risk awareness was measured in terms of knowledge of the links between smoking and disease. The overall age-adjusted prevalence of smoking was 33.1% in men and 29.0% in women, but wide variations were observed across country samples. Significant sex differences were found in only a minority of cases. The inclusion of respondents who stated that they had sometimes smoked in the past substantially reduced variations in prevalence across country samples. Beliefs in the health benefits of not smoking were consistently associated with smoking behaviour. Awareness of the link between smoking and lung cancer was uniformly high, but awareness of the role of smoking in heart disease varied considerably across country samples, and averaged only 64.4% in men and 62.9% in women. In the majority of countries, risk awareness was greater among smokers than non-smokers. The results suggest that in this selected sector of the population of young adults in Europe, sex differences in smoking are relatively minor, robust associations between attitudes and smoking behaviour can be identified, and there are major gaps in risk awareness. PMID- 7773122 TI - Radioautography in cellular and molecular biology. AB - A general survey is presented on the most important applications of radioactive compounds as well on fresh as on fixed tissues, with and without immunological reactions, at light and electron microscopic levels. Its goal is to show their flexibility and their extended applications, in comparison with the non radioactive methods. But radioautography applies as well to non-cellular aspects, such as electrophoretic and chromatographic techniques, permitting a complementary and even more detailed exploration of the molecules investigated at cellular levels. A rapid information is given on the exact denomination of the radioautographic methods, on hybridization in situ and in vitro, on the different blotting techniques used for DNA, RNA and proteins, on semi-quantitation and quantitation of DNA-RNA hybrids, on radioimmunodection by fluorography and on newer filmless radioautographic systems. The organ, body and pharmacological radioautographies belong to the nuclear medicine and have been evocated briefly. PMID- 7773123 TI - Proceedings of the 4th International Symposium on Radioautography, satellite symposium of the 25th annual meeting of the Clinical Electron Microscopy Society of Japan. Matsumoto, Japan, September 28-October 2, 1993. PMID- 7773124 TI - Incorporation of 3H-amino acids by endometrial stromal cells during decidualization in the mouse. A radioautographical study. AB - The incorporation of 3H-amino acids by endometrial stromal cells was analyzed by radioautography during decidualization in the mouse. 3H-proline was administered to 5- and 6-day pregnant mice and to virgin mice in estrus used as controls. 3H tryptophan was administered to 6-day pregnant mice. The animals were killed 30 min. after the injection of the radioactive label. The quantitative analysis of the radioautograms showed that the concentration of silver grains per unit area due to 3H-proline incorporation was higher in decidual and predecidual cells on the fifth and sixth day of pregnancy than in fibroblasts of virgin mice. Considering the pregnant endometrium by itself, the incorporation of both 3H proline and 3H-tryptophan was higher in fully differentiated decidual cells and predecidual cells than in fibroblasts of the periphery of the endometrium and involuting decidual cells. These results show a clear correlation between different endometrial regions recognized by morphological criteria and their metabolic activity. The data also show that different cells of the pregnant endometrium have different metabolic activities, independently of the precursor that was used. PMID- 7773125 TI - Age-related changes of male mouse submandibular gland: a morphometric and radioautographic study. AB - The DNA synthesis and the changes of cell population kinetic of aging male mouse submandibular glands were studied by light and electron microscopic radioautography from embryonic day 19 to 21 months postnatal. At the embryonic day 19, the gland consisted of developing acinar cells (49%), intercalated duct (ICD) (37%), juxta-acinar (JA) (3%) and striated duct (SD) cells (11%). At birth, JA cells increased rapidly to 32%, thereafter decreased gradually. At 1 month of age, granular convoluted tubule cells appeared and increased rapidly in number with age. They reached a maximum at 6 month after birth. Then they appeared to decrease gradually from 6 to 21 months. The most conspicuous feature of the aged submandibular glands was the regressive changes of the granular ducts. The extent and height of the granular ducts as well as the content of mature secretory granules decreased. These changes may play an important role during the development of mice, because the granular duct synthesizes many biological factors. The 3H-thymidine labeling index of each cell type of male mouse submandibular glands reached a peak 1 day after birth and decreased with aging. The labeling index of intercalated duct cells was higher than the others and persisted for a long time. On the other hand, the labeling indices of the other cells were significantly depressed at one week after birth. From these observations on morphology, it was also shown that ICD cells were concerned with the generation of the other cell types. PMID- 7773126 TI - Uptake site of lansoprazole, a proton pump inhibitor, in human fundic mucosa: possible relevance with fibroblast and Helicobacter pylori. AB - To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms. PMID- 7773127 TI - Use of confocal laser scanning microscopy in radioautographic study. AB - Confocal laser scanning microscopy was used to visualize the radioautograph at the light-microscope level. Confocal reflectance images from developed silver grains were overlaid with the differential interference contrast image of the tissue. With this technique, a well-focused radioautograph can be taken of both tissue sections and all of the silver grains dispersed in the thick emulsion layer. Further application of this microscopy is discussed. PMID- 7773128 TI - Heterogeneous distribution of 125I-insulin binding sites in the liver of fed and fasted mice. AB - A microradioautography made three min. after intravenous injection of 125I insulin was used to study the distribution of insulin binding sites in the liver of fed and fasted mice. A substantial specific binding of 125I-insulin to liver parenchymal cells could be seen in these mice, whereas radioautographs from animals injected with 125I-insulin plus an excess of unlabelled insulin showed only trace amounts of silver grains. In both fed and fasted mice, a density gradient of the binding from the periportal zone to the perivenous zone was evident, and the binding in each zone was significantly higher in the fasted mice than in the fed mice. PMID- 7773129 TI - Ultrastructural and radioautographic studies on DNA synthesis in Leydig cells on aging mouse testis. AB - A morphological observation and a radioautographic study were carried out to detect the ultrastructure and aging changes of DNA synthesis of the Leydig cells, whose structure has been observed and the area of the lipid droplets in the cytoplasm calculated. The observation by electron microscopy showed that Leydig cells contained abundant mitochondria and endoplasmic reticulum and that the area of the lipids in the cytoplasm changed with aging. Only little lipid droplets were found in embryonic and early postnatal stages, but they increased from postnatal two weeks onwards and no significant differences were found from 9 months to 21 months. The DNA synthesis in these cells was not vigorous at embryonic day 19, explored by light microscopic radioautography 1 hr. following a single injection of 3H-thymidine. The labeling index increased slightly before six months of age and reached its peak at 9 months. There was no significant difference found in the number of labelled cells from that time on. A relatively high level was maintained at adult and senescent periods. Our results demonstrate that the generation of the Leydig cells contained plentiful lipid droplets was vigorous at adult and senescence. PMID- 7773130 TI - Brain activity of a rat reflects apparently the stimulation of acupuncture. A radioautography using 2-deoxyglucose. AB - To confirm a relationship between the central nervous system and the acupuncture, the response was examined in the rat brain using radioautography with tritiated 2 deoxyglucose, after stimulation of some acupoints. Eight groups, of a total of 27 rats were submitted to acupuncture at 6 different acupoints (Zusanli, Renzhong, Tianshu, Shenmen, Neiguan, Yongquan) and control, with or without electric pulses or with anesthesia respectively, prior to the injection with isotopic deoxyglucose. A hundred twenty cryosections were cut from a freshly frozen brain and exposed on single-coated X-ray films. The results showed that the acupuncture on the four acupoints of Zusanli, Tianshu, Shenmen and Neiguan enhanced the activity of the neocortex, the limbic cortex and the thalamic nuclei in comparison with the control group. The acupoints on Renzhong and Yongquan depressed the activity on the thalamic nuclei and the midbrain. The anesthesia with pentobarbital concealed the most activity on the whole area of the brain, which hardly responded to any stimulation of acupuncture. These results lead to the suggestion that the brain may reflect the signals by the stimulation of acupuncture and change the activity depending upon each acupoint. PMID- 7773131 TI - Study on nucleic acid synthesis in mouse retina and retinal pigment epithelium by radioautography. AB - The ocular tissues of ddY mice from embryonic 9 to postnatal day 14 were labelled in vitro with 3H-thymidine or 3H-uridine. After radioautography, the radioautographs were observed by light and electron microscopes. The labeling indices (L.I.) with 3H-thymidine or grain numbers with 3H-uridine were calculated and the area (microns 2) of cell organelles in both labelled and unlabelled retinal cell with 3H-thymidine were measured by image analysis. The L.I. of retinal cells were low in the beginning then increased and reached a peak at P3, while the L.I. of retinal pigment epithelium (RPE) increased and reached a peak at P7. The L.I. of both retinal and PE cells disappeared at P14. However, the L.I. of anterior region were more than those of equaterial and posterior regions in both retinal and PE cells. The results of the image analysis showed that the average area of cell organelles, both labelled and unlabelled retinal cells decreased from E9 to P14. The grain numbers of retina labelled with 3H-uridine increased until P1 then decreased, while the numbers of RPE increased and reached a peak at P3 whereafter they declined. No significant differences were detected among the three regions. PMID- 7773132 TI - Distribution of humanized MAb 425 (EMD 62,000) in rats and specific localization in tumor-bearing nude mice. AB - The murine MAb 425 (IgG2a) directed against human epidermal growth factor receptor is considered to have therapeutic potential in glioma patients. In order to circumvent immune response in clinical use, the MAb 425 was humanized by CDR grafting (IgG1). We have studied the distribution of reshaped MAb 425 (EMD 62,000) in Wistar rats and the specific localization in female nude mice bearing human mamma carcinoma xenografts. The 125I-labelled MAb 425 was administered intravenously in a single dose (1 mg/kg) using unspecific human IgG1 antibody as control. The biodistribution was investigated both quantitatively and by whole body autoradiography. The autoradiographs showed a selective uptake of radioactivity by the tumour tissue. 15 days after administration, radioactivity was bound exclusively to the tumour. Similar results were obtained with the murine monoclonal antibody. Quantitative studies exhibited a tumour-blood ratio of about 5. The study demonstrates that the humanized MAb 425 is selectively localized in human mamma carcinoma xenografted to athymic mice. PMID- 7773133 TI - Zonal variations of types II, IX and XI collagen mRNAs in rat epiphyseal cartilage chondrocytes: quantitative evaluation of in situ hybridization by image analysis of radioautography. AB - The spatial-temporal distribution of the mRNAs for type IX and type XI collagens were compared to that of type II collagen mRNA in the tibial epiphyseal plate cartilage of normal growing rats. The mRNAs were detected by in situ hybridization with radio-labelled specific probes and visualized by radioautography. The areas covered by the resulting silver grains were quantified by computer assisted image analysis. The areas in chondrocytes of each zone of the epiphyseal plate cartilage, which correspond to the stages of chondrocyte development and function were determined. Types II, IX and XI mRNAs were present to some extent in chondrocytes of all zones. The distributions of type II and type IX collagen mRNAs were similar with the highest concentrations in the proliferative zone, and the lowest in the resting and calcifying zones chondrocytes. In contrast, type XI collagen mRNA had a different distribution, with the lowest concentration in the resting zone chondrocytes and a significant decrease in the calcifying zone chondrocytes. These patterns correlates with the changes in chondrocyte function, and may reflect the roles of the type IX and type XI collagens. The data show that computer assisted image analysis of in situ hybridization radioautographic images is a precise, rapid tool for analysing differences in gene expression. PMID- 7773134 TI - Light and electron microscopic radioautographic studies on macromolecular synthesis in digestive organs of aging mice. AB - For the purpose of analyzing the changes of macromolecular synthesis in aging animals, we have developed methodologies for quantitative light and electron microscopic radioautography. The methodologies were applied to DNA, RNA, protein, glucides and lipids syntheses of digestive organs, especially of the liver and the pancreas of aging strain ddY mice, demonstrating the incorporations of respective precursors, 3H-thymidine, 3H-uridine, 3H-leucine, 3H-glucosamine, 35S sulfuric acid and 3H-glycerol. Characteristic differences have been observed between the respective macromolecular syntheses in respective aging groups, from prenatal (embryonic day 19) to postnatal newborn period (postnatal day 1), from suckling (postnatal day 3) to weaning (postnatal day 14), juvenile (postnatal 1 month), young adult (postnatal 2 month) and senescent periods (6 and 12 months up to 2 years). These results are extensively analyzed and reviewed. PMID- 7773136 TI - Distribution of [1,2-3H]taurine in the skin of adult and newborn mice studied by microradioautography. AB - In vivo light microscopic radioautography was used to demonstrate the distribution of taurine in adult and newborn mice at 30 min. and 3 hrs. after the injection of 3H-taurine. This study showed that the injected taurine was present in free form in the skin. Radioautographically, it was found that in the adult a very high density of taurine was found over the epidermis and external root sheaths near the opening of the hair follicles. The external root sheath just below the insertion of the sebaceous glands and the peripheral part of the sebaceous glands showed a high taurine distribution. Connective tissue in the dermis, however, showed low uptake of taurine. In the neonate mouse, the density of injected taurine in both the epidermis and the external root sheath was lower than that the density in the connective tissue in the dermis. We report these findings in detail and discuss some of the functional roles of taurine in the skin. PMID- 7773135 TI - Recent progress in whole-body radioautography. AB - We review whole-body radioautography for water-soluble substances and its applications studied to date in our laboratory. To transfer the whole-body section onto a glass slide, Japanese paper was inserted between frozen block and adhesive tape before sectioning. Then the section was dried together with the paper and adhesive tape in a cryotome and applied onto the glass slide coated with a mixture of egg-albumin and glycerin. The whole-body section was transferred to slide and contacted with the film in vacuum. By using these techniques, we review the glucose and taurine metabolism, the glucose-6 phosphatase activity and the insulin receptor. PMID- 7773137 TI - Microchannel array detector for quantitative electronic radioautography. AB - The microchannel array detector provides direct electronic detection and real time imaging of radioactive tracers in samples that traditionally have been imaged by film radioautography. The technology of the detector is described, and the main benefits of this new technology, speed and precise quantitation, are illustrated with practical results. The instrument response to a 14C dilution series (range of 10(5)) was linear over the whole range. Results from the microchannel array detector are compared to results obtained with liquid scintillation counting (LSC) and densitometry of film radioautographs. Because the instrument response is linear and consistent from day to day, it is not necessary to routinely include calibration standards as is required for film. The 14C counting efficiency was found to be essentially constant for different tissues in a whole body microtome section. As with LSC, results reported as counts per min. (CPM) are independent of counting time. Quantitative results were obtained with assays for chloramphenicol acetyl transferase in two min. and little as 0.2 DPM/mm2 of 32P was detected in seven min. PMID- 7773138 TI - Effect of biological response modifiers on growth and cell proliferation of human tumor xenografts in nude mice. AB - The effect of biological response modifiers on macroscopic tumor growth and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alpha) as well as granulocyte macrophage colony-stimulating factor (GM-CSF) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in combination did not substantially affect the course of tumor growth, however, they did influence the pattern of tumor growth. There was also only a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decrease of the labeling index and to a significant decrease of the animal weight which indicates that the first two effects may be partly due to the toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to inhibition at higher doses. Although there is no substantial direct antineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a protective effect against cachexia. PMID- 7773140 TI - Granulation in amine-storage organelles of mouse megakaryocytes: X-ray microprobe analysis and radioautography. AB - The mechanisms and the processes of the storage of bivalent cations, ATP and 5 hydroxytryptamine (5HT) in the precursors of the amine-storage organelles of megakaryocytes were studied at the electron microscopic level. Although the precursors of the amine-storage organelles in the megakaryocytes fixed with glutaraldehyde and osmium tetroxide were empty, the electron opaque granules were observed in these organelles of the freeze-substituted megakaryocytes cut onto ethylene glycol. X-ray microprobe analysis demonstrated that they contained P, Mg and Ca. Quantitative differences in bivalent cations in the granules were not observed between megakaryocytes and blood platelets. Electron opaque uranaffin reaction products were observed in the precursors of the amine-storage organelles of the megakaryocytes after treatment with the uranaffin reaction for ATP. However, few chromaffin positive granules were observed in the precursors of the amine-storage organelles after the chromaffin reaction for monoamines. Radioautographic analysis demonstrated that blood platelets avidly took up 3H-5HT but megakaryocytes were not able to accumulate 3H-5HT in vivo. These results indicate that megakaryocytes do not yet acquire the well developed uptake system of 5HT in vivo, while they readily accumulate cations and ATP in the precursors of the amine-storage organelles. PMID- 7773139 TI - Localization of Na, K-ATPase isoforms in the hypothalamus of the rat. AB - In situ hybridization histochemistry with synthetic oligonucleotide probes was used to localize mRNAs encoding three isoforms of the catalytic (alpha) subunit and one isoform of the (beta) subunit of the Na, K-ATPase in rat hypothalamus using contact film radioautography. 3H-Ouabain binding to specific anatomical nuclei in the hypothalamus was determined using a quantitative radioautographic technique previously developed in our laboratory. Specific hybridization was found with oligonucleotide probes for mRNA encoding alpha 1, alpha 2, alpha 3, beta 1 isoforms of the Na, K-ATPase. High levels of hybridization signal for alpha 3 and beta 1 were found in ventromedial hypothalamus, supraoptic nucleus, paraventricular nucleus and the anterior hypothalamic area. Very low levels of hybridization for all isoforms were found in the optic chiasm. mRNAs encoding alpha 1 and alpha 2 isoforms were expressed at lower levels than alpha 3. The distribution of alpha 2 was consistent with expression in glial cells. Generally, levels of alpha 1 mRNA were higher in the arcuate nucleus than in other hypothalamic regions and very low levels were found in the anterior hypothalamic area. 3H-Ouabain binding was relatively diffuse, consistent with the localization of the synthesized Na, K-ATPase protein in cellular processes. The number of 3H ouabain binding sites in the paraventricular nucleus was significantly lower than other hypothalamic nuclei studied. The results suggest that Na, K-ATPase isoforms may be differentially expressed in hypothalamic nuclei. PMID- 7773141 TI - Biosynthesis of glycosaminoglycans in the endometrium during the initial stages of pregnancy of the mouse. AB - Significant changes in the synthesis of glycosaminoglycans occur during the transformation of stromal cells of the endometrium into decidual cells which takes place during the initial stages of pregnancy in mice. Hyaluronic acid, which is practically absent in the endometrium of virgin mice, increases dramatically on the fifth day of pregnancy, reaching its maximal concentration on day 6 followed by a 50% decrease on day 7. Changes in hyaluronic acid concentration also occur in pseudopregnant mice indicating that they are not related to the presence of the embryo in the uterus. The absolute concentration of the sulfated glycosaminoglycans, e.g., heparan sulfate, dermatan sulfate and chondroitin sulfate in the decidua did not change significantly. There was, however, a striking decrease of their biosynthesis in pregnant and pseudopregnant mice when compared to virgin mice, as shown by the use of radioactive inorganic sulfate as a precursor for the study of in vivo synthesis. A radioautographical analysis confirmed that the highest incorporation of radioactive sulfate was observed in virgin endometria when compared to pregnant ones. These studies also have shown a characteristic pattern of labeling in different regions of the endometrium that repeats itself during the different days of pregnancy. PMID- 7773142 TI - Improvements in bio-mechanical adhesion of screws used in medical field: first application in spinal surgery. AB - Metallic screws are becoming more and more useful to join bones or for prosthesis support in orthopaedic and dental surgery. High biocompatible materials such as titanium alloys and hydroxyapatite ceramics are making possible the realization of stable fixation devices utilizable in load-bearing applications. The mechanical and biological anchorage of metallic screws to the bone depends on many factors: mechanical screws-bone thread matching, use of cements between bone and screw, chemical-physical treatments of screw surface, use of screw coverage films based on osteointegrating ceramics or active bioglasses, use of porous coverage films to induce bone ingrowth into the pore, and so on. The first step of the research, the aim of the present paper, is the comparison among screws of different shapes and geometric characteristics in order to find the best macromechanical system versus the different load conditions. Static and dynamic tests are applied to the screws mounted on segments of pig spine, in order to measure the mechanical characteristics of the system under tension (pull-out), bending on the principal planes along the axis of the screw and fatigue loads. Physical analysis, obtained using energetic charged particles, such as SEM, RBS, and AES, are used to characterize the screw surface compositions and morphology. PMID- 7773143 TI - Valid method to evaluate the slope of Fourier transformed spectrum for the analysis of biological rhythm fluctuation. AB - Influences of lower frequency components of power spectrum calculated from biological rhythm data on the spectral slope were examined and the validity of conventional method to calculate the spectral slope was tested. Heart-beat-period data obtained from the electrocardiogram of rats were cut into two successive data sets, each of them was converted into power spectrum density by the fast Fourier transform, and the power spectra were compared with each other. The results showed that two spectra were overlapped only in the frequency range higher than a frequency about 15 times that of the dominant one, which means that the lower frequency components are not always the same and thus, the regression line by which the spectral slope is determined is considerably affected by the components. To evaluate the spectral slope, regression lines of spectra were obtained in three methods and their slopes were compared with each other. The methods were: "conventional" method, in which the weight of a frequency component was independent of the frequency (i.e., equal-weight = 1); "weight" method, in which the weight was the wave number included in the rhythm data; and "limited data" method, where the weight was 1 and lower-frequency components were excluded. The results showed that there was not a large difference between the slopes in cases where the spectrum looked rather linear. However, in cases of considerably curved spectra the difference was large and the "weight" method may be the most reasonable to use, and in cases of short data length the "limited data" method should be avoided. PMID- 7773144 TI - Reinforcement of bone cement around prostheses by pre-coated wire coil: a finite element model study. AB - The longevity of cemented total joint replacements, namely total hip arthroplasty (THA), depends on the integrity of the cement per se and interfaces of the metallic stem-cement and bone-cement, and stress/stress transmission and its distribution. A simple coil made of stainless steel wire was placed around a tapered stem in a simulated cement mantle to counteract the radial- and hoop stresses created by the stem loading. Two-dimensional axisymmetric finite element analysis was performed to elucidate the level of the stress and its distribution with and without the wire coil. The results suggest that the peak stresses distributed throughout the cement may be reduced by more than one half, via the incorporation of a wire coil, confirming the mechanical test results, which showed an average fracture load of 3.70 +/- 1.13 kN for pure bone cement control and 9.02 +/- 1.54 kN for the wire coil reinforced specimens. These results indicate that the reinforcement of the cement mantle with a wire coil in the distal end of the hip stem prosthesis could reduce the hoop-stresses, which may results in reduced stresses in the bone and cement interface. Consequently, loosening of the interfaces of the bone-cement and cement-stem could be reduced due to the enhanced fatigue life of the bone cement mantle with favorable stress distribution at the distal tip of the stem. PMID- 7773145 TI - The effect of two types of cross-linking on some mechanical properties of collagen. AB - Samples of collagen were cross-linked by two different methods: (a) glutaraldehyde and (b) a combination of dehydrothermal treatment and cyanamide. The elastic modulus, the ultimate tensile strength (fracture stress), strain to failure, work of fracture, and fracture toughness were measured before and after cross-linking in ambient laboratory conditions, and during immersion in water. These tests were all performed over a range of strain rates. For collagen tested in the wet condition, it was found that cross-linking increased the elastic modulus from approximately 25-30 MPa, to between 55 and 60 MPa, but there was little effect on fracture stress, and strain to failure was reduced. The work of fracture of the collagen decreased on cross-linking. Cross-linking had the same effect on the elastic modulus, fracture stress, and strain to failure of dry collagen, but the work of fracture was unaffected. In conclusion, cross-linking increased the elastic modulus, reduced the strain to failure, and had little effect on the fracture stress of collagen under the present experimental conditions. PMID- 7773146 TI - Direct or indirect skin lipid-ordering effect of pyrrolidone carboxylate sodium after topical treatment with penetration enhancers. AB - The structural changes in the lipid of the excised skin of nude mice and the porcine stratum corneum was investigated by in vitro treatment with vitamin C, oleic acid, or DMSO. The CH2 stretching vibrational peaks of lipid near 2920 cm-1 (asymmetric) and 2850 cm-1 (symmetric) shifted to higher wavenumber due to the lipid-disorder after in vitro treatment with above enhancers. The spectral shift of the asymmetric CH2 band was more sensitive than that of the symmetric CH2 band. The higher wavenumber of CH2 stretching bands decreased gradually to the lower region after co-treatment or posttreatment with pyrrolidone carboxylate sodium (PCA Na). Such a decrease was dependent on the PCA Na concentration and the time of treatment. The higher the concentration of PCA Na used, the lower value of the permeability coefficient of vitamin C through the excised skin and the downward spectral shift of asymmetric CH2 band were obtained. When PCA Na coexisted with vitamin C in the cell donor compartment, a competitive effect between PCA Na and vitamin C was found. The oleic acid was supposed to directly insert it into the lipid structure to form a rigid structure, leading to larger spectral shift of both stretching bands but lesser restoring ability after PCA Na treatment. However, DMSO only displaces water from the lipid head groups and protein domain of skin to indirectly loosen the lipid structure, resulting in lesser spectral shift of the CH2 stretching bands to higher region, which was easier and better restoration after PCA Na application. The PCA Na enabled to restore the disordered lipid structure to order state might be attributed to PCA Na previously penetrated into skin and then absorbed water to directly or indirectly rearrange the disordered lipid bilayer structure. PMID- 7773147 TI - Patterns of drug resistance parameters in adult leukemia. AB - P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6 Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment. PMID- 7773148 TI - P-glycoprotein expression in acute myeloblastic leukemia analyzed by immunocytochemistry and flow cytometry. AB - Using the APAAP technique, we assessed the reactivity of five monoclonal antibodies, JSB1, C219, Mab 57, 2F8 and MRK16, to gp 170 in 60 cases of de novo acute myeloid leukemia (AML) and 13 relapses. Reactivity, varied between the five antibodies, and positivity was obtained with 2F8 > JSB1 > MRK16 > Mab57 > C219. Sixteen of the 60 cases were also studied by flow cytometry. In 10 cases, the results with the two techniques corresponded, in the other 6 cases, flow cytometry proved more sensitive than APAAP in detecting small amounts of gp170. In the flow cytometry analysis, the cells fixed in methanol and paraformaldehyde were more fluorescent than unfixed samples or those fixed in paraformaldehyde or methanol alone. Our results thus reveal that positivity for gp 170 depends on various factors, including the specificity of the monoclonal antibodies, the techniques used and the preservation of the samples. This suggests the need for a clear standardization of the methods to detect gp170. PMID- 7773149 TI - Comparative analysis of cytokines released by bone marrow stromal cells from normal donors and B-cell chronic lymphocytic leukemic patients. AB - We studied the production of cytokines (G-CSF, GM-CSF, IL-6, LIF and IL-10) by bone marrow stromal cells of five untreated patients with B-CLL, in Rai stage 0, I and II, and of 8 healthy subjects. The production of G-CSF, GM-CSF, LIF and IL 10 did not differ significantly between controls and B-CLL patients. However, the ability of stromal cells to release IL-6 in response to LPS was decreased in all patients: 36 +/- 5 ng/ml versus 123 +/- 47 ng/ml for normal controls (p < 0.004). Moreover, a soluble activity that inhibited hematopoietic colony formation was detected in B-CLL stromal cell conditioned media. Some potential inhibitors were envisaged and the results indicated an increased production of TGF-beta by B-CLL stromal cells compared to normal stromal cells (respectively 53 +/- 10 versus 15 +/- 4 ng/ml, p < 0.03). The reduced capacity of B-CLL stromal cells to produce IL 6 was associated with this excessive release of TGF-beta; indeed, addition of anti-TGF-beta neutralizing antibody to B-CLL stromal cells, before LPS stimulation, totally normalized the production of IL-6. TGF-beta and IL-6 were also measured in serum samples from normal subjects and B-CLL patients. No significant difference was seen in the production of total TGF-beta (bioactive and latent forms) between normal and B-CLL sera but the mean level of bioactive protein in B-CLL sera was increased in comparison with normal sera (1.74 +/- 0.44 versus 0.67 +/- 0.2 ng/ml, p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773150 TI - Multiple patterns of MDM-2 deregulation in human leukemias: implications in leukemogenesis and prognosis. AB - The human analogue of the mouse double minute-2 (MDM-2) protein binds to p53 protein and abrogates its tumor-suppressing activity. MDM-2 overexpression may represent an alternative mechanism to p53 mutation for escaping the p53-mediated growth control. Interestingly, multiple MDM-2 protein isoforms have been described and the possibility of functional differences between various isoforms has been raised. Previously, we demonstrated significant MDM-2 mRNA overexpression in human leukemias and suggested that MDM-2 overexpression may be a marker of aggressiveness of the disease. Polyclonal antibodies (Ab) have been generated to detect various isoforms of the MDM-2 protein. Using these Abs, we confirmed MDM-2 protein overexpression in leukemias. Furthermore, we observed heterogeneity in the isoforms expressed in various types of leukemias. In addition, we demonstrated that analysis by flow cytometry could be used as a diagnostic tool for detecting altered MDM-2 protein expression in leukemias. Here we review and expand our initial observations and confirm MDM-2 mRNA and protein overexpression by reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and western blot analyses. Understanding the possible role of MDM-2 oncogene expression in leukemias may establish the scientific basis for new therapeutic approaches. PMID- 7773151 TI - The role of decreased retinoblastoma protein expression in acute myelomonocytic and monoblastic leukemias. AB - The results of different investigators show that lack of p105 expression is relatively common in human myeloid leukemias, especially in monocytic leukemias. This suggests that loss of p105 expression could contribute to the altered growth control of these cells. So far no clear data exist which show that low p105 levels in AML blasts predict a poor therapy outcome. Therefore it is not very likely that p105 expression will become a strong prognostic factor for the different treatment strategies in AML. PMID- 7773153 TI - Intestinal T-cell lymphoma with massive tissue and blood eosinophilia mediated by IL-5. AB - A case of enteropathy associated T-cell lymphoma (EATCL) in a 62-year-old female with a previous history of coeliac disease, complicated during the clinical course by massive blood and tissue eosinophilia is described. The patient's serum contained a factor capable of stimulating the in vitro growth of eosinophilic colonies (CFU-Eo), that was absent in the serum of normal donors. We suggest that such factor was Interleukin-5 (IL-5), as indicated by the presence in the monoclonal tumor T cells of IL-5 encoding mRNA, usually absent in the normal enterocytes of the jejunum. PMID- 7773152 TI - Chlorambucil, vincristine and cytarabine (COA) treatment of low grade lymphomas. AB - Forty-five patients with stage III-IV low grade non-Hodgkin's lymphoma (NHL) were treated with a non-intensive polychemotherapy regimen including chlorambucil vincristine and cytarabine (Ara-C), termed COA, for a total of 366 courses, beginning in June 1986. Grade 4 myelotoxicity occurred in only 4/45 patients. No treatment related death was observed. All patients were evaluable for response. Overall, 38 (84%) objective responses, including 31 (69%) complete responses (CR), were observed. At a median follow-up of 57 (21-84+) months, only 8 deaths occurred. Twenty-seven (60%) patients are still disease-free. All disease-free patients were in their first CR. The seven-year estimated survival is 71% and the estimated 7-year progression-free survival (PFS) was 48%. The estimated probability of complete responders to be disease-free at 6 years is 78%. Pretreatment laboratory parameters (serum levels of thymidine kinase, LDH and TNF alpha showed a good prognostic relevance at using univariate analysis. At multivariate analysis, only the pretreatment serum levels of TNF-alpha were significantly associated with a higher CR achievement probability (p = 0.02) and a longer PFS (p = 0.02). We established a risk model for clinical outcome based on these 3 parameters. Patients having all parameters within the normal range at diagnosis, showed a very good prognosis (100% 7-year PFS and survival), while patients with all parameters increased had a very poor prognosis (0% 7-year PFS and 22% 7-year survival). In conclusion, COA treatment appears to be a non-toxic and very effective treatment for low-grade non-Hodgkin's lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773154 TI - Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country. AB - The link between Hodgkin's disease (HD) and Epstein-Barr virus (EBV) is well documented in childhood and here the same hypothesis has been examined in adults, by comparing cases from an industrialized and a developing country. In this study the prevalence of EBV markers in nodal lesions of adult HD were compared in 21 patients from France (Fr) and 25 from Algeria (Al), all clinically staged during 1990-1992. Median age was 29 years. Histologic subtypes included lymphocytic predominance (LP) Fr 1; nodular sclerosis (NS) Fr 16, Al 16; mixed cellularity (MC) Fr 4, Al 9. EBV markers examined included expression of latent membrane protein (LMP) in Reed-Sternberg and Hodgkin cells (RSC) by immunochemistry; EBV DNA and -RNA in situ hybridization (ISH); EBV-DNA by polymerase chain reaction (PCR). Results showed that RSC were LMP-positive in 4 (2 NS, 2 MC) French and 7 (3 NS, 4 MC) Algerian. All LMP+ cases were also positive for EBV DNA-RNA ISH. ISH was positive in RSC of 33% of the French and 72% of Algerian patients (p < 0.02). The positivity was more frequent in MC (77%) than in other histologic types (45%). The EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). Conclusion. The discrepancy between PCR and ISH results may be due to the lesser sensitivity of the ISH technique, or, alternatively, to the presence of EBV in the lymphoid cells surrounding RSC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773155 TI - Cytokine dysregulation in chronic graft versus host disease. AB - Cytokines play a key role in the pathogenesis of chronic Graft versus Host Disease (cGVHD) and various studies have shown abberant production of cytokines by immune cells from GVHD patients. Based on these findings and others showing that high TNF levels precede the development of GVHD, we evaluated inflammatory cytokine levels following BMT and during the development of cGVHD. In this study, patients undergoing bone marrow transplantation (BMT) who consequently developed chronic GVHD were analyzed as to their cytokine production during cGVHD and this was correlated with their clinical manifestations. A positive correlation was found between the severity as well as the number of major clinical complications and high levels of inflammatory cytokines (IL-1 beta IL-6 and TNF alpha) compared to control patients or to normal donors. Patients undergoing BMT who did not develop GVHD, did not produce high levels of IL-1 beta IL-6 or TNF. High levels of cytokines may be used as a tool for assessing novel therapeutic modalities and response to GVHD treatment. PMID- 7773156 TI - A retinoic acid resistant HL-60 cell clone sensitive to N-(4-hydroxyphenyl) retinamide-mediated clonal growth inhibition. AB - Among the Retinoic Acid (RA) derivatives, retinamides, and in particular N-(4 hydroxyphenyl) retinamide (4-HPR), are currently being investigated in selected cases of cancer chemoprevention. The cellular target range, however, seems to be limited, as cells of hemopoietic origin are virtually incapable of terminal differentiation upon addition of the compound. We have reconsidered the effect of 4-HPR on HL-60 cells by taking advantage of a mutant clone, generated in our laboratory, unresponsive to RA but highly responsive to dimethylsulfoxide (DMSO). We show here that this clone, upon addition of 4-HPR, although unable of undergoing full differentiation, shows considerable reduction of clonal growth. Moreover, the combination of 4-HPR and RA resulted in a much greater effect than the administration of 4-HPR alone. We suggest that 4-HPR and RA, at least in terms of mediating growth inhibition, may follow different metabolic pathways. PMID- 7773157 TI - A simplified method for cryopreservation of hematopoietic stem cells with -80 degrees C mechanical freezer with dimethyl sulfoxide as the sole cryoprotectant. AB - A simplified method for cryopreservation was developed with 10% dimethylsulfoxide (DMSO) as the sole cryoprotectant without rate-controlled freezing. This method produced high recovery rate for mononucleated cells (87%) and elevated trypan blue viability (90%). Autologous peripheral blood stem cells (PBSCs) and bone marrow cells with plasma and 10% DMSO were frozen and stored in a -80 degrees C mechanical freezer. Eleven patients with solid and hematological malignancies were transplanted with autologous bone marrow or PBSCs. The median number of infused mononuclear cells (MNC) and CD34+ cells were 3.63 x 10(8)/Kg and 4.80 x 10(6)/Kg, respectively. The median number of infused post-thawing CFU-GM was 20 x 10(4)/Kg. All patients showed a rapid and sustained engraftment. The mean times to reach a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 11 and 13 days, respectively. All patients are alive and 10 in unmaintained complete remission for 3-9 months after transplantation. These results show the efficacy of this simplified cryopreservation technique that will be useful for institutions without rate-controlled freezing facilities. PMID- 7773158 TI - Polymyositis associated with Ki-1 lymphoma. AB - We report here a case of acute polymyositis associated with a Ki-1 non-Hodgkin's lymphoma (NHL). This anaplastic large cell malignant lymphoma was a primary T cell NHL lymphoma of the bone marrow. The malignant cells expressed the CD30 (Ki 1), CD3, and CD4 antigens, the beta chain of the interleukin 2 receptor (CD25), and the betaF1 antigen (alpha/beta T-cell receptor). Chemotherapy and high dose methylprednisolone pulse therapy were initiated. However, no clinical improvement was noticed, because the patient rapidly died of an acute respiratory distress syndrome. To our best knowledge, this represents the first case of Ki-1 lymphoma associated with Polymyositis. PMID- 7773160 TI - c-mpl expression in hematologic disorders. AB - The c-mpl gene encodes a member of the hematopoietic cytokine receptor superfamily. This gene was discovered through the study of a murine retrovirus which induces an acute myeloproliferative syndrome in mice. MPLV (for myeloproliferative leukemia virus) has transduced a truncated and constitutively activated form of the c-mpl receptor chain. The c-mpl ligand is unknown, but recent data indicate that it could specifically regulate thrombocytopoiesis. This review focuses on the expression of the c-mpl gene in a large series of human hematopoietic pathologies by Northern blot analysis. Barely detectable transcript levels were detected in normal bone marrow (BM) and in BM samples from chronic myeloproliferative disorders, plasmocytoma, Burkitt lymphoma or acute lymphoid leukemia. In contrast, high levels of c-mpl expression were detected in 45% of acute myeloid leukemia (AML). No correlation was found between c-mpl expression and the French-American-British classification subtype of AML. However c-mpl expression correlated with CD34 expression, and unfavorable cytogenetic abnormalities, defining a subgroup of AML with a low rate of complete remission. In myelodysplasia, c-mpl expression was elevated in 44% of chronic myelomonocytic leukemia (CMML), 42% of refractory anemia with excess myeloblasts (RAEB), and RAEB in transformation to acute leukemia (RAEBt), but not in refractory anemia (RA) and RA with ringed sideroblasts (RARS). In CMML, there was no correlation between c-mpl expression and any prognostic factor tested, nor with the course of the disease. The biologic significance of c-mpl expression in RAEB and RAEBt is probably different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773159 TI - Legionnaires' disease during induction of remission chemotherapy for acute nonlymphocytic leukemia. AB - Two patients with acute nonlymphocytic leukemia (ANLL) who developed neutropenia, bilateral lung infiltrates, and did not respond to conventional antibiotic therapy nor amphotericin B are described. Clinical awareness and suspicion of Legionnaires' disease (LD) and early administration of erythromycin lead to their cure before the diagnosis of LD was confirmed. PMID- 7773161 TI - DNA fingerprint analysis in acute leukemias. AB - Restriction fragment length polymorphism (RFLP) analysis by Southern blotting or direct in-gel hybridization is a routine procedure in any genetic laboratory. Minisatellites and simple repeat probes for RFLP analysis have proved to be highly informative genetic markers, depending on their degree of homology and index of heterozygosity. Several of these probes have considerable individualization potential, thus yielding 'fingerprint' pattern. In the setting of acute leukemia DNA fingerprint (DNA-F) analysis is able to provide considerable information concerning the genetic instability of the leukemic clone. DNA-F is capable of detecting randomly occurring genetic alterations of unknown localization and to identify new hotspots of malignant transformation. As DNA-F analysis is not likely to be hampered by the effects of chemotherapy or DNA methylation, altered fingerprints may be regarded as characteristic of the leukemic clone. With the introduction of polymerase chain reaction (PCR) and increasing sensitivity, DNA-F analysis is likely to be of significant importance in monitoring minimal residual disease in human leukemia. PMID- 7773162 TI - p53 expression in non-Hodgkin's lymphomas: a marker of p53 inactivation? AB - The p53 gene located in the short arm of chromosome 17 at position 17p13, is involved in the negative regulation of cellular growth. p53 mutation seems to be the most frequent genetic alteration found in human cancer. Mutant conformation of the p53 gene is associated with cell proliferation and tumour progression, and in most cases implies p53 stabilization, which renders the p53 protein detectable through the use of immunohistochemical techniques. p53 expression is a frequent finding in high grade lymphomas of either B or T cell lineage, having been detected in 30% of cases in our series. The focal presence of p53+ cells was seen in a wide range of low and high grade lymphomas, including lymphadenitis and reactive tonsils. In 37.5% of cases this increased expression of p53 was secondary to mutation in highly conserved regions (exons 5-8). Unlike findings reported in other tumours, in lymphomas, p53 expression seems to be secondary to genetic alterations other than p53 mutation. Initial data suggest that the MDM2 protein could be involved in inactivating p53 protein in most of these cases. Finally, p53 expression has been found to be a poor prognostic marker in high grade B-cell lymphomas in a large series of cases. High p53 expression was associated with a short survival, this relation being stronger in cases with simultaneous bcl2 expression. PMID- 7773164 TI - Chromosomal deletions in myelodysplasia. AB - There are two major classes of genes implicated in human tumorigenesis, the oncogenes and the tumour suppressor genes. In haematological malignancies most emphasis has been placed upon the recurring translocations in which the juxtaposition of two gene sequences has resulted in the activation of an oncogene. Chromosomal loss rather than translocation is the most frequent karyotypic abnormality in the myelodysplastic syndromes, a heterogeneous group of clonal malignant blood disorders characterised by dyshaematopoiesis and/or impaired maturation of haemopoietic cells with frequent evolution to acute leukaemia. Recent attention has focused on the loss of genetic material as a result of chromosomal monosomy or deletion in the myelodysplastic syndromes. The most frequently reported deletions in these myeloid syndromes are of chromosomes 5, 20 and 7. Deletions of chromosomes 11, 12, and 13, although more rarely observed, are also characteristics of the myelodysplastic syndromes. It is probable that the deleted chromosomal bands give the location for as yet unidentified myeloid specific tumour suppressor loci and there is considerable interest in the cloning of these genes. This review discusses the three most frequently observed deletions in MDS; 7q deletion, 5q deletion and 20q deletion taking into account recent evidence on the respective critical regions of gene loss and the role of candidate genes. PMID- 7773163 TI - T cells in multiple myeloma: is this a reliable population to count on as antitumor effector cells? AB - Multiple Myeloma (MM) is still a long way from being cured. Disease evolution has been associated with a number of phenotypic and functional alterations in T cells, indicating that a progressive deterioration of cellular immunity might facilitate the negative outcome. Despite these correlations, specific interactions between tumor and T cells have been demonstrated indicating that a population liable to be exploited as antitumor effector cells exists in vivo. This review aims at recording some evidence obtained in our laboratory demonstrating that MM T cells, despite the variety of their alterations, can still generate potent antitumor activity. Adequate stimulation, however, is required to exploit this ability. PMID- 7773165 TI - The contribution of Auer rods to the classification and prognosis of myelodysplastic syndromes. AB - Auer rods were first recognized at the beginning of this century. Their presence soon became considered to be an unequivocal manifestation of a leukemic process. Possibly influenced by this long-held assumption, in 1982 the French-American British co-operative group (FAB) incorporated the presence of Auer rods into a classification system of the myelodysplastic syndromes that remains in widespread clinical usage today. Although unsubstantiated at the time, the presence of Auer rods was suggested to indicate a rapidly progressive disorder and a poor prognosis. In the absence of studies confirming the utility of Auer rods as a diagnostic criterion, the FAB classification system of myelodysplastic syndromes has been widely used to allocate therapy. In this review we examine the early descriptions of Auer rods and critically evaluate the studies examining the value their presence has in the classification and prognosis of patients with myelodysplastic syndromes. PMID- 7773166 TI - Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma. AB - This report describes the clinical characteristics, treatment associated toxicity, and follow-up of fifty-eight patients with plasma cell--dyscrasias treated with high dose chemotherapy and total body irradiation (TBI) at a single institution. Following TBI, 36 patients received anti-B cell monoclonal antibody (MoAb)-treated autologous bone marrow, 21 patients received anti-CD6 cell MoAb treated allogeneic bone marrow to deplete T cells, and one patient received unpurged bone marrow from a syngeneic donor. Evaluation after high dose chemotherapy and bone marrow transplantation (BMT) demonstrated 26 complete responses (CR), 26 partial responses (PR), 2 non-responders, 1 not yet evaluated, and three toxic deaths. Fourteen of 36 patients who underwent autologous BMT are alive free from progression at 18 (range 5 to 68) months post transplant (post BMT); of these, 11 remain in continuous complete response at 16 (range 5 to 68) months post-BMT. Seven of 21 patients who underwent allogeneic BMT are alive free from progression at 30 (range 4 to 44) months post-BMT; of these, three patients remain in continuous complete response at 43 (range 33 to 45) months post-BMT. These data suggest that high dose chemotherapy with TBI followed by MoAb purged BM can be performed with acceptable toxicity and high tumor response rates. PMID- 7773167 TI - An update on allogeneic marrow transplantation for myelodysplastic syndrome. AB - Ninety-three patients with myelodysplastic syndrome with either excess blasts or life-threatening cytopenia received cyclophosphamide and total body irradiation (88 patients) or busulfan (5 patients) followed by allogeneic (90 patients) or syngeneic (3 patients) marrow infusion. Thirty-eight patients are disease-free survivors between 1.8 and 11.3 years (median 6.1 years) after transplantation. The median Karnofsky performance status of the survivors is 100%, and only 2 have a performance status of < 80%. Eighteen patients relapsed and the remaining 37 died without evidence for relapse. The 5-year actuarial disease-free survival, relapse, and non-relapse mortality rates are 40%, 29%, and 44%, respectively. The actuarial relapse rate was higher among patients with excess blasts at the time of transplantation compared to those without excess blasts (49% vs. 4%, p = 0.0001), resulting in a lower disease-free survival (31% vs. 54%, p = 0.07). Increasing age was associated with a lower disease-free survival (p = 0.02). In a multivariate analysis, younger age, shorter disease duration, and absence of excess blasts were associated with improved outcome. We recommend that patients with myelodysplasia with appropriate marrow donors, especially patients less than age 40, undergo marrow transplantation early during the disease course, before the disease progresses or life-threatening complications develop. PMID- 7773168 TI - A procedure for detecting structural domains in proteins. AB - A procedure is described for detecting domains in proteins of known structure. The method is based on the intuitively simple idea that each domain should contain an identifiable hydrophobic core. By applying the algorithm described in the companion paper (Swindells MB, 1995, Protein Sci 4:93-102) to identify distinct cores in multi-domain proteins, one can use this information to determine both the number and the location of the constituent domains. Tests have shown the procedure to be effective on a number of examples, even when the domains are discontinuous along the sequence. However, deficiencies also occur when hydrophobic cores from different domains continue through the interface region and join one another. PMID- 7773169 TI - Identification of a eukaryotic-like protein kinase gene in Archaebacteria. AB - Primary sequence patterns based on known conserved sites in eukaryotic protein kinases were used to search for eukaryotic-like protein kinase sequences in a six frame translation of the bacterial subsection of GenBank. This search identified a previously unrecognized eukaryotic-like protein kinase gene in three related methanogenic archaebacteria, Methanococcus vannielii, M. voltae, and M. thermolithotrophicus. The proposed coding sequences are located in orthologous open reading frames (ORFs): ORF547, ORF294, and ORF114, respectively. The C terminus of the ORFs contains 9 of the 11 subdomains characteristically conserved within the eukaryotic protein kinase catalytic domain. The N-terminus of the ORFs is similar to a putative glycoprotease in Pasteurella haemolytica and its homologue in Escherichia coli, the orfX gene. This is the first report of a eukaryotic-like protein kinase sequence observed in Archaebacteria. PMID- 7773171 TI - A brief and subjective history of contractility. PMID- 7773173 TI - Thermodynamics of heme-induced conformational changes in hemopexin: role of domain-domain interactions. AB - Hemopexin is a serum glycoprotein that binds heme with high affinity and delivers heme to the liver cells via receptor-mediated endocytosis. A hinge region connects the two non-disulfide-linked domains of hemopexin, a 35-kDa N-terminal domain (domain I) that binds heme, and a 25-kDa C-terminal domain (domain II). Although domain II does not bind heme, it assumes one structural state in apo hemopexin and another in heme-hemopexin, and this change is important in facilitating the association of heme-hemopexin with its receptor. In order to elucidate the structure and function of hemopexin, it is important to understand how structural information is transmitted to domain II when domain I binds heme. Here we report a study of the protein-protein interactions between domain I and domain II using analytical ultracentrifugation and isothermal titration calorimetry. Sedimentation equilibrium analysis showed that domain I associates with domain II both in the presence and absence of heme with Kd values of 0.8 microM and 55 microM, respectively. The interaction between heme-domain I and domain II has a calorimetric enthalpy of +11 kcal/mol, a heat capacity (delta Cp) of -720 cal/mol.K, and a calculated entropy of +65 cal/mol.K. By varying the temperature of the centrifugation equilibrium runs, a van't Hoff plot with an apparent change in enthalpy (delta H) of -3.6 kcal/mol and change in entropy (delta S) of +8.1 cal/mol.K for the association of apo-domain I with domain II was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773170 TI - Differentiation of peptide molecular recognition by phospholipase C gamma-1 Src homology-2 domain and a mutant Tyr phosphatase PTP1bC215S. AB - Activated epidermal growth factor receptor (EGFR) undergoes autophosphorylation on several cytoplasmic tyrosine residues, which may then associate with the src homology-2 (SH2) domains of effector proteins such as phospholipase C gamma-1 (PLC gamma-1). Specific phosphotyrosine (pTyr)-modified EGFR fragment peptides can inhibit this intermolecular binding between activated EGFR and a tandem amino and carboxy-terminal (N/C) SH2 protein construct derived from PLC gamma-1. In this study, we further explored the molecular recognition of phosphorylated EGFR988-998 (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly, I) by PLC gamma-1 N/C SH2 in terms of singular Ala substitutions for amino acid residues N- and C terminal to the pTyr (P site) of phosphopeptide I. Comparison of the extent to which these phosphopeptides inhibited binding of PLC gamma-1 N/C SH2 to activated EGFR showed the critical importance of amino acid side chains at positions P+2 (Ile994), P+3 (Pro995), and P+4 (Gln996). Relative to phosphopeptide I, multiple Ala substitution throughout the N-terminal sequence, N-terminal sequence, N terminal truncation, or dephosphorylation of pTyr each resulted in significantly decreased binding to PLC gamma-1 N/C SH2. These structure-activity results were analyzed by molecular modeling studies of the predicted binding of phosphopeptide I to each the N- and C-terminal SH2 domains of PLC gamma-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773172 TI - A recombinant human hemoglobin with asparagine-102(beta) substituted by alanine has a limiting low oxygen affinity, reduced marginally by chloride. AB - A recombinant (r) mutant hemoglobin (Hb) with Asn-102(beta) replaced by an Ala (N102A(beta)) has been prepared by PCR amplification of a mutagenic DNA fragment and expression of the recombinant protein in yeast. The side chain of Asn 102(beta) is part of an important region of the alpha 1 beta 2 interface that undergoes large structural changes in the transition between the deoxy and oxy conformations. Three natural mutant Hbs with neutral substitutions of Thr, Ser, or Tyr at this site have low oxygen affinities because a hydrogen bond between Asn-102(beta) and Asp-94(alpha) in normal HbA was considered to be absent in these mutants, thereby destabilizing the oxy conformation in favor of the deoxy conformation. This proposal has been tested by expression of an rHb containing alanine at position 102(beta); alanine was chosen because its methyl side chain cannot participate in hydrogen bond formation, yet it is small enough not to disrupt the subunit interface. The nature of the desired replacement was established by sequencing the entire mutated beta-globin gene as well as the tryptic peptide containing the substitution. Further characterization by SDS PAGE, isoelectric focusing, HPLC analysis, mass spectrometry, amino acid analysis, and sequencing of the mutant tryptic peptide confirmed the purity of the rHb. Its oxygen binding curve (2.4 mM in heme) in the absence of chloride showed that it had a very low oxygen affinity with a P50 of 42 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773174 TI - Interleukin-1 beta converting enzyme: a novel cysteine protease required for IL-1 beta production and implicated in programmed cell death. AB - Interleukin-1 beta converting enzyme is the first member of a new class of cysteine proteases. The most distinguishing feature of this family is a nearly absolute specificity for cleavage at aspartic acid. This enzyme has been the subject of intense research because of its role in the production of IL-1 beta, a key mediator of inflammation. These studies have culminated in the design of potent inhibitors and determination of its crystal structure. The structure secures the relationship of the enzyme to CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans, suggesting that members of this family function in cell death in vertebrates. PMID- 7773175 TI - Conformational stability of HPr: the histidine-containing phosphocarrier protein from Bacillus subtilis. AB - The conformational stability of the histidine-containing phosphocarrier protein (HPr) from Bacillus subtilis has been determined using a combination of thermal unfolding and solvent denaturation experiments. The urea-induced denaturation of HPr was monitored spectroscopically at fixed temperatures and thermal unfolding was performed in the presence of fixed concentrations of urea. These data were analyzed in several different ways to afford a measure of the cardinal parameters (delta Hg, Tg, delta Sg, and delta Cp) that describe the thermodynamics of folding for HPr. The method of Pace and Laurents (Pace CN, Laurents DV, 1989, Biochemistry 28:2520-2525) was used to estimate delta Cp as was a global analysis of the thermal- and urea-induced unfolding data. Each method used to analyze the data gives a similar value for delta Cp (1,170 +/- 50 cal mol-1K-1). Despite the high melting temperature for HPr (Tg = 73.5 degrees C), the maximum stability of the protein, which occurs at 26 degrees C, is quite modest (delta Gs = 4.2 kcal mol-1). In the presence of moderate concentrations of urea, HPr exhibits cold denaturation, and thus a complete stability curve for HPr, including a measure of delta Cp, can be achieved using the method of Chen and Schellman (Chen B, Schellman JA, 1989, Biochemistry 28:685-691). A comparison of the different methods for the analysis of solvent denaturation curves is provided and the effects of urea on the thermal stability of this small globular protein are discussed. The methods presented will be of general utility in the characterization of the stability curve for many small proteins. PMID- 7773176 TI - Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase. AB - Colipase (Mr 10 kDa) confers catalytic activity to pancreatic lipase under physiological conditions (high bile salt concentrations). Previously determined 3 A-resolution X-ray structures of lipase-colipase complexes have shown that, in the absence of substrate, colipase binds to the noncatalytic C-terminal domain of pancreatic lipase (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 359:159-162; van Tilbeurgh et al., 1993a, Nature 362:814-820). Upon lipid binding, conformational changes at the active site of pancreatic lipase bring a surface loop (the lid) in contact with colipase, creating a second binding site for this cofactor. Covalent inhibition of the pancreatic lipase by a phosphonate inhibitor yields better diffracting crystals of the lipase-colipase complex. From the 2.4-A-resolution structure of this complex, we give an accurate description of the colipase. It confirms the previous proposed disulfide connections (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 359:159-162; van Tilbeurgh et al., 1993a, Nature 362:814-820) that were in disagreement with the biochemical assignment (Chaillan C, Kerfelec B, Foglizzo E, Chapus C, 1992, Biochem Biophys Res Commun 184:206-211). Colipase lacks well-defined secondary structure elements. This small protein seems to be stabilized mainly by an extended network of five disulfide bridges that runs throughout the flatly shaped molecule, reticulating its four finger-like loops. The colipase surface can be divided into a rather hydrophilic part, interacting with lipase, and a more hydrophobic part, formed by the tips of the fingers. The interaction between colipase and the C-terminal domain of lipase is stabilized by eight hydrogen bonds and about 80 van der Waals contacts. Upon opening of the lid, three more hydrogen bonds and about 28 van der Waals contacts are added, explaining the higher apparent affinity in the presence of a lipid/water interface. The tips of the fingers are very mobile and constitute the lipid interaction surface. Two detergent molecules that interact with colipase were observed in the crystal, covering part of the hydrophobic surface. PMID- 7773177 TI - Mutations of surface residues in Anabaena vegetative and heterocyst ferredoxin that affect thermodynamic stability as determined by guanidine hydrochloride denaturation. AB - The stability properties of oxidized wild-type (wt) and site-directed mutants in surface residues of vegetative (Vfd) and heterocyst (Hfd) ferredoxins from Anabaena 7120 have been characterized by guanidine hydrochloride (Gdn-HCl) denaturation. For Vfd it was found that mutants E95K, E94Q, F65Y, F65W, and T48A are quite similar to wt in stability. E94K is somewhat less stable, whereas E94D, F65A, F65I, R42A, and R42H are substantially less stable than wt. R42H is a substitution found in all Hfds, and NMR comparison of the Anabaena 7120 Vfd and Hfd showed the latter to be much less stable on the basis of hydrogen exchange rates (Chae YK, Abildgaard F, Mooberry ES, Markley JL, 1994, Biochemistry 33:3287 3295); we also find this to be true with respect to Gdn-HCl denaturation. Strikingly, the Hfd mutant H42R is more stable than the wt Hfd by precisely the amount of stability lost in Vfd upon mutating R42 to H (2.0 kcal/mol). On the basis of comparison of the X-ray crystal structures of wt Anabaena Vfd and Hfd, the decreased stabilities of F65A and F65I can be ascribed to increased solvent exposure of interior hydrophobic groups. In the case of Vfd mutants E94K and E94D, the decreased stabilities may result from disruption of a hydrogen bond between the E94 and S47 side chains. The instability of the R42 mutants is also most probably due to decreased hydrogen bonding capabilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773178 TI - Hydrogen bonding motifs of protein side chains: descriptions of binding of arginine and amide groups. AB - The modes of hydrogen bonding of arginine, asparagine, and glutamine side chains and of urea have been examined in small-molecule crystal structures in the Cambridge Structural Database and in crystal structures of protein-nucleic acid and protein-protein complexes. Analysis of the hydrogen bonding patterns of each by graph-set theory shows three patterns of rings (R) with one or two hydrogen bond acceptors and two donors and with eight, nine, or six atoms in the ring, designated R2(2)(8), R2(2)(9), and R1(2)(6). These three patterns are found for arginine-like groups and for urea, whereas only the first two patterns R2(2)(8) and R2(2)(9) are found for asparagine- and glutamine-like groups. In each case, the entire system is planar within 0.7 A or less. On the other hand, in macromolecular crystal structures, the hydrogen bonding patterns in protein nucleic acid complexes between the nucleic acid base and the protein are all R2(2)(9), whereas hydrogen bonding between Watson-Crick-like pairs of nucleic acid bases is R2(2)(8). These two hydrogen bonding arrangements [R2(2)(9)] and R2(2)(8)] are predetermined by the nature of the groups available for hydrogen bonding. The third motif identified, R1(2)(6), involves hydrogen bonds that are less linear than in the other two motifs and is found in proteins. PMID- 7773179 TI - A comparison of X-ray and NMR structures for human endothelin-1. AB - Direct comparisons between the recently solved X-ray and NMR structures of human endothelin-1 with respect to secondary structure, RMS deviations, surface accessibilities, and side-chain conformers indicate important differences in conformation, especially in the C-terminus, but also in the central loop region, that are important for defining the specificity of binding. These differences are larger than seen for other X-ray and NMR structures that have been compared. Comparisons between the X-ray structure and the NMR NOE constraints highlight the regions of flexibility and environment-induced diversity in the endothelin structures. PMID- 7773180 TI - Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase. AB - The Thermus thermophilus 3-isopropylmalate dehydrogenase (IPMDH) and Escherichia coli isocitrate dehydrogenase (ICDH) are two functionally and evolutionarily related enzymes with distinct substrate specificities. To understand the determinants of substrate specificities of the two proteins, the substrate and coenzyme in IPMDH were docked into their respective binding sites based on the published structure for apo IPMDH and its sequence and structural homology to ICDH. This modeling study suggests that (1) the substrate and coenzyme (NAD) binding modes of IPMDH are significantly different from those of ICDH, (2) the interactions between the substrates and coenzymes help explain the differences in substrate specificities of IPMDH and ICDH, and (3) binding of the substrate and coenzyme should induce a conformational change in the structure of IPMDH. PMID- 7773181 TI - A procedure for the automatic determination of hydrophobic cores in protein structures. AB - An algorithm is described for automatically detecting hydrophobic cores in proteins of known structure. Three pieces of information are considered in order to achieve this goal. These are: secondary structure, side-chain accessibility, and side-chain-side-chain contacts. Residues are considered to contribute to a core when they occur in regular secondary structure and have buried side chains that form predominantly nonpolar contacts with one another. This paper describes the algorithm's application to families of proteins with conserved topologies but low sequence similarities. The aim of this investigation is to determine the efficacy of the algorithm as well as to study the extent to which similar cores are identified within a common topology. PMID- 7773182 TI - A fast, economical and efficient method for DNA purification by use of a homemade bead column. AB - A fast, efficient and economical method for purification of DNA from various sources by the use of silica particles packed in homemade bead columns is described. The method is a further development of the method devised by Carter and Milton (1), improved by the introduction of a column operated with a vacuum system. The method is highly suitable for multiple sample handling in the preparation of DNA for sequencing and other purposes. Protocols are devised for plasmid minipreparation, gel elution and purification of DNA from solutions e.g. enzyme reactions. PMID- 7773183 TI - Susceptibility of Helicobacter pylori to antimicrobial agents: effect of sulglycotide. AB - H. pylori is regarded as a primary etiologic factor in gastric disease and the therapies now include a combination of antimicrobial agents with antiulcer drugs. Here, the effect of a new gastroprotective agent, sulglycotide, on the in vitro anti-H. pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin was assessed. The assays in the absence of sulglycotide gave MIC value 0.10mg/L for erythromycin, 0.12mg/L for amoxycillin, 0.15mg/L for tetracycline and 14mg/L for metronidazole, while sulglycotide alone gave MIC value of 20mg/L. The sulglycotide at its optimal dose (5mg/L) evoked a 4-fold enhancement in the MIC of amoxycillin, 5-fold in tetracycline, and 8.3-fold in erythromycin, while the MIC of metronidazole improved 3.5-fold at 10mg/L sulglycotide. The results point towards the advantage of combination therapy of sulglycotide and antibiotics for H. pylori eradication. PMID- 7773184 TI - Detection of M2 antibodies in patients with recurrent urinary tract infection using an ELISA and purified PBC specific antigens. Evidence for a molecular mimicry mechanism in the pathogenesis of primary biliary cirrhosis? AB - Primary Biliary Cirrhosis (PBC) is a chronic liver disease of unknown aetiology. The main characteristic feature of the disease is the presence of circulating antimitochondrial antibodies (AMA) to components (collectively named M2) of the mitochondrial 2-oxo-acid multienzyme complexes; pyruvate, oxoglutarate and branched chain oxo-acid dehydrogenase complexes. As these enzymes are phylogenetically conserved, AMA also exhibit reactivity against a range of microorganisms. PBC patients have an increased incidence of recurrent urinary tract infection (UTI) compared to other chronic liver disease controls. Interestingly, we have recently detected low titre AMA in patients with a history of recurrent UTI but normal liver function using crude bovine heart mitochondrial preparations and immunoblotting techniques. Here we confirm these findings using purified M2 antigens and ELISA. We found that 52% of "normal" subjects with a history of recurrent UTI had AMA specifically to M2 antigens. The percentage was significantly higher than that found for chronic liver disease (19%, p < 0.01) and normal controls (4%, p < 0.001). These results support our hypothesis for molecular mimicry in PBC. We propose that a bacterial trigger, possibly resulting from recurrent UTIs, is responsible for initiating an autoimmune response in a predisposed host because of a cross-reactivity between mitochondrial and bacterial antigens. PMID- 7773185 TI - Regression of LNCaP human prostate tumor xenografts in athymic nude mice by 13 cis-retinoic acid and androgen ablation. AB - The present study was designed to investigate the effects of 13-cis-retinoic acid (13-cis-RA) (100 micrograms/mouse/day) and androgen ablation (castration) alone and in combination on growth of a human prostatic carcinoma line (LNCaP) transplanted to athymic nude mice as an experimental model. The results of these studies suggest that; (1) androgen ablation (castration) significantly decreased the size of LNCaP xenograft as compared to untreated animals; (2) when 13-cis-RA was administered to nude mice carrying established tumors (0.51 +/- 0.04 cm3), the tumor size was significantly reduced as compared to untreated controls (0.65 +/- 0.06 cm3 versus 1.63 +/- 0.12 cm3). About 50% of the animals in this group showed xenografts necrosis followed by complete regression of tumors by five months; (3) the combination of androgen ablation and 13-cis-RA treatment to nude mice carrying tumors showed synergistic effect in decreasing the tumor size. These results indicate that combination therapies based on androgen ablation and retinoid administration may be a useful approach for the treatment of prostate cancer. PMID- 7773186 TI - Inhibition and kinetic alterations by excess free ATP and ADP of the ATP diphosphohydrolase activity (EC 3.6.1.5) from rat blood platelets. AB - ATP diphosphohydrolase (EC 3.6.1.5) catalyzes the hydrolysis of diphospho- and triphosphonucleosides and is activated by divalent cations. The enzyme described in rat blood platelets hydrolyzes Ca(2+)-ATP and Ca(2+)-ADP with a high affinity for these Ca(2+)-nucleotide complexes as substrates. In the present paper, we demonstrate that free ATP or free ADP induces inhibition and kinetic alterations of the enzyme from rat blood platelets. From these results, we draw conclusions about the binding of free nucleotides to the enzyme and their action as inhibitors with respect to calcium-nucleotide complex. PMID- 7773187 TI - Possible interaction of haemoglobin with a low Mr GTP-binding protein, ram p25. AB - Haemoblobin (Hb) was observed to inhibit the GDP/GTP exchange activity of a low M(r) GTP-binding protein, ram p25. Hb also inhibited the [32P]GTP-hydrolysis activity of ram p25. These inhibitory effects of Hb were lost after incubation of Hb at 80 degrees C for 3 min, indicating that the ternary tetrameric structure of Hb is essential for the inhibitory effects on ram p25 activities. Hb did not inhibit [35S]GTP gamma S-binding of nucleotide-free ram p25. Methaemoglobin (MetHb) also inhibited both [3H]GDP-dissociation and [32P]GTP-hydrolysis activities of ram p25 in a very similar manner to Hb. The results strongly suggest that Hb may suppress physiological function(s) of ram p25 in vivo by inhibiting both [32P]GTP-hydrolysis and [3H]GDP-dissociation of ram p25. PMID- 7773190 TI - Positive regulatory role of cAMP on alkaline phosphatase activity and proliferation of mitogen stimulated B lymphocytes. AB - Effect of dibutyryl cyclic adenosine monophosphate (dbt cAMP) on alkaline phosphatase (APase) of mitogen stimulated murine B lymphocytes was studied. Addition of dbtcAMP to lipopolysaccharide (LPS) stimulated B cells enhanced APase activity in a dose dependent and synergistic manner. dbtcAMP also stimulated the proliferative response of LPS treated B lymphocytes. On the other hand, when B lymphocytes stimulated with anti-immunoglobulin (anti-Ig) were treated with dbtcAMP neither DNA synthesis nor APase activity was enhanced. These results suggest that cAMP is a potent synergistic activator of APase in B lymphocytes committed to proliferation. PMID- 7773188 TI - Storage of rat liver for plasma membrane isolation. AB - We described a procedure for the preservation of rat liver which makes possible the isolation of plasma membranes after 10 days storage at -70 degrees C. The yield of plasma membranes obtained from the liver tissue kept at -70 degrees C for 10 days (3.43 +/- 0.08 mg protein/10 g wet liver) was not different statistically (P > 0.05) from the yield of freshly obtained plasma membranes (3.32 +/- 0.05 mg protein/10 g wet liver). However, a significantly low yield (2.65 +/- 0.08; P < 0.01) was obtained from 90 days stored rat liver when compared with the immediate isolation. Plasma membrane Na+, K+ ATPase and 5'nucleotidase activities of the stored liver for 10 days were not different statistically (P > 0.05) from the enzyme activities of the freshly isolated membrane fractions. In contrast there was a significant decrease (p < 0.0001) in the activities of both plasma membrane Na+, K+ ATPase and 5'nucleotidase activities of 90 days stored rat liver at -70 degrees C when compared with immediate isolation. Considering the electron microscopic findings; we observed that the preservation of the integrity of the plasma membrane fractions obtained from fresh and frozen livers for 10 and 90 days seemed to be parallel to the biochemical results. Therefore we suggest that, storage of rat liver tissue for 10 days make feasible to maintain the experimental design and give convenience for obtaining intact plasma membrane fractions. PMID- 7773189 TI - N-glycosylated polypeptides synthesized in the early phase of AcNPV infected insect cells. AB - Infected cell specific polypeptides (ICSP) in Autographa californica nuclear polyhedrosis virus (AcNPV) infected Spodoptera frugiperda cell line, Sf9, were radiolabelled with [14C] mannose and the labelled proteins were monitored at various time intervals. A major glycoprotein of molecular size of 64 kDa appears as early as 3h post infection (p.i.) which peaks at 12h p.i., but in presence of tunicamycin this protein is not labelled. Two other glycoproteins of molecular size 67 kDa and 63 kDa appear at 12h post infection. The glycosylation of these and eight other cellular proteins is also inhibited by tunicamycin. AcNPV propagated in tunicamycin treated Sf9 cells was found to cause delayed infectivity. PMID- 7773191 TI - Alteration of the microenvironment in plasma membranes of rat enterocytes after Escherichia coli heat stable enterotoxin treatment: effect on protein kinase C activity. AB - Plasma membranes isolated from Escherichia coli heat stable enterotoxin (STa) treated rat enterocytes were studied in respect to protein kinase C activity and fluidity change. Pretreatment of enterocytes with STa increased the membrane bound protein kinase C activity about 5 fold as compared to control. STa treatment made the membrane more fluid as evident from a higher phospholipid/cholesterol ratio and greater unsaturated fatty acid levels. Moreover, the phase transition temperature of the STa treated membrane appeared to be significantly lower than that of the corresponding control membrane, thereby further indicating a rise in fluidity of the membrane in the former case. Our results, therefore, suggested that following STa enterotoxin treatment an appropriate fluid environment in the rat intestinal cell membrane was essential for the activation of protein kinase C. PMID- 7773192 TI - Oxidative stress induced by ethanol in rat hepatocyte cultures. AB - Many controversies still exist with regard to the relationship between alcoholic intoxication and the occurrence of an oxidative stress. To attempt to resolve this question, first we investigated the induction by acute ethanol intoxication of lipid peroxidation in primary rat hepatocyte cultures using simultaneously two indices for each sample. When considering conjugated-diene indice, any lipid peroxidation elevation could be observed, whereas a net increase of extracellular free malondialdehyde was noted at 5 hours of incubation. These results led us to estimate the intracellular pool of low molecular weight iron which is known to be the iron species catalytically active in hydroperoxide degradation. An early enhancement of +20-30% of cellular low molecular weight iron was observed. Thus the discrepancy between conjugated dienes and malondialdehyde could be ascribed to an increase of hydroperoxide degradation into malondialdehyde by the transient cellular pool of low molecular weight iron. Lipid peroxidation and low molecular weight iron augmentation were linked to ethanol metabolism, since both were suppressed by the addition of 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Superoxide dismutase activity was increased in the early incubation time (1 hour) and then markedly reduced. We conclude that ethanol metabolism can induce a lipid peroxidation accompanied by an elevation of intracellular pool of low molecular weight iron and a decrease of superoxide dismutase activity. PMID- 7773193 TI - Investigation of the effects of Zn2+ and Cu2+ on the K+ transport in yeast mitochondria. Evidences for the involvement of a Zn(2+)-binding protein in the K+/H+ exchange. AB - Effect of Zn2+ and Cu2+ were studied on the spontaneous swelling of yeast mitochondria in potassium acetate. (i) Whatever the pH, Cu2+ stimulated the swelling. (ii) Zn2+ inhibited or stimulated the swelling depending both on pH of the medium and of its concentration: it induced an inhibition of the K+/H+ exchange at pH 6.8 and a stimulation at pH 7.7; at pH 7.4, Zn2+ inhibited the swelling at low concentration and stimulated the swelling at higher concentration. (iii) The thiol reagent mersalyl prevented the inhibition by Zn2+ whereas N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoate) prevented the stimulation by Zn2+: this allowed to hypothesize that two distinct Zn(2+)-binding sites were involved in the inhibition and in the stimulation of the swelling of yeast mitochondria suspended in potassium acetate. PMID- 7773194 TI - Nucleotides-induced cytosolic calcium transient and plasma membrane permeability in Chang human liver cells. AB - Extracellular nucleotides induce changes in cytosolic free Ca++ and also increase plasma membrane permeability to Ca++ ions in Chang human liver cells. Ca++ permeability induced by nucleotides is reversible and inactivated immediately upon removal of agonist. Stimulated cells transferred into the fresh medium and re-exposed to nucleotides demonstrate reopening of Ca++ channel without stimulation of Ca++ transient. Relative potencies of nucleotides to induce membrane permeability and Ca++ transient were: UTP > ATP > gamma-S-ATP > ADP (non hydrolyzable ATP analogues and AMP had no effect). The permeability is not affected by specific inhibitors of voltage-operated calcium channels (verapamyl,cis-diltiazem and nifedipin). Nucleotides do not produce plasma membrane damages at concentrations up to 1 mM, as shown by exclusion of the propidium iodide. There are at least two types of nucleotides receptors in Chang cell membrane: P2y subtype receptors which is responsible for generation of the Ca++ transient, and P2x subtype receptors which lead to the opening of plasma membrane Ca++ channels upon activation. PMID- 7773195 TI - Complete nucleotide sequences of Marburg virus genes 5 and 6 encoding VP30 and VP24 proteins. AB - Nucleotide sequences of the genes 5 and 6 of the Marburg virus, Popp strain, were determined. ORFs encoding polypeptides VP30 (281 a.a., MW 32,640) and VP24 (253 a.a., MW 28,621) were found. The putative transcription start and stop signals for viral RNA-dependent RNA polymerase were revealed for both genes. Overlapping of genes 5 and 6 was shown. The deduced amino acid sequences of VP30 and VP24 proteins displayed significant homology with the analogous proteins of another filovirus, the Ebola virus (33% and 37%, respectively). The VP24 appeared to have a hydrophobic amino acid composition; content of hydrophobic amino acids was 40.7%. Model of VP24 location in the virion was suggested. PMID- 7773196 TI - Coenzyme cycles and metabolic control analysis: the determination of the elasticity coefficients from the generalised connectivity theorem. AB - Metabolic control analysis allows one to express the elasticity coefficients (which describe the "local" kinetic features of enzymes) in terms of the control coefficients (quantitative indicators of the "global" control properties). However, when coenzymes (or metabolites linked by conservation constraints) are present in the pathway this procedure yields the "apparent" values of elasticity coefficients that correspond to the kinetic responses of the enzymes to such a simultaneous change of the coenzyme forms which leaves the total concentration of these forms unchanged (e.g., NAD+ + NADH in the glycolysis). We show that a generalised connectivity theorem (Kholodenko et al, Eur. J. Biochem. (1994) 225, 179-186) makes it possible to express the elasticity coefficients with respect to every coenzyme form separately. Such expressions include (i) the control coefficients and (ii) the responses to changes in the total concentrations of the coenzymes. PMID- 7773197 TI - Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. AB - Twenty-four edible plants were investigated for the presence of melatonin, heretofore considered to be a molecule found only in the animal kingdom. The amount of melatonin in different plants varied greatly with highest melatonin being present in plants of the rice family. Melatonin was identified by radioimmunoassay and verified by high performance liquid chromatography with fluorescence detection. Feeding a diet containing plant products rich in melatonin to chicks increased radioimmunoassayable levels of melatonin in their blood. Likewise, melatonin extracted from plants inhibited binding of [125I]iodomelatonin to rabbit brain. Thus, melatonin ingested in foodstuffs enters the blood and is capable of binding to melatonin binding sites in the brain of mammals. PMID- 7773198 TI - An improved simple colorimetric method for quantitation of non-transferrin-bound iron in serum. AB - A simple method for direct quantitation of non-transferrin-bound iron (NTBI) in serum is introduced. NTBI was separated from serum by adding excess nitrilotriacetic acid disodium salt (NTA) to serum to form an Fe-NTA complex and then ultrafiltrated using a micro-filter. The NTBI in the ultrafiltrate was quantitated using a bathophenanthroline-based method. The optimal detection condition and several potential confounding factors were investigated. The actual measurements to samples in vivo and in vitro showed that this method is very practical. PMID- 7773199 TI - Specificity of inhibition of muscle glycogen phosphorylase b by flavins. AB - The inhibition of glycogen phosphorylase b from rabbit skeletal muscles by the derivatives of riboflavin, FMN, FAD, and 2', 3', 4', 5'-tetraacetylriboflavin substituted in positions 6 and 8 of the isoalloxazine part of the flavin molecule is found to be cooperative (the Hill coefficient, h, exceeds 1.0). The modification of the flavin molecule slightly changes the value of the Hill coefficient, but results in the increase of the "half-saturation" concentration [I]0.5. PMID- 7773201 TI - Polymorphism of the angiotensin I converting enzyme gene in essential hypertensive patients. AB - Insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene has been associated with ischemic heart disease and hypertension. The D allele reportedly correlates with myocardial infarction and it has been suggested that it may serve as the basis of population-based risk assessment. Similarly, determining whether there is an ACE allele pattern associated with hypertension could be useful in developing screening strategies. Previous reports have not shown consistent findings in Caucasian and Japanese population groups, some having a predominance of the I allele. Although African Americans have the highest prevalence of hypertension in the world, their ACE gene polymorphism frequencies have not been clearly defined. We studied the allele and genotype frequencies in this group, consisting of 133 essential hypertensive subjects, and compared their findings with those reported from normotensive African Americans and from other racial groups. The black patients had a different allele distribution than the other populations in that the D was more common than the I allele, occurring at a rate of 59.7%. The most common genotype was DD and it was present in 42.5% of the hypertensive subjects in contrast to the ID genotype which was the most commonly reported genotype in normotensive individuals. The genotype pattern (frequencies of II, ID, DD) was significantly different (p < 0.005, 2 df) from Japanese and Caucasian (Scotland and Australia) populations. There was no common allele or genotype distribution amongst these diverse hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773200 TI - Localized mitochondrial dysfunction in canine myocardial ischemia. AB - Effects of myocardial ischemia on mitochondrial enzymes and mitochondrial DNA (mtDNA) were examined using the model of Ameroid constriction of canine cardiac vessels. Endocardium supplied by constricted coronary arteries was found to have significantly lower citrate synthase and complex IV activities compared to values obtained from either epicardium supplied by constricted vessels or endocardium supplied by unconstricted coronary arteries. Neither significant differences in mtDNA copy number nor changes in respiratory complexes I, III and V were detected. These results suggest that highly localized, specific mitochondrial enzyme changes result from chronic myocardial ischemia. PMID- 7773202 TI - Purification and properties of 6-phosphogluconate dehydrogenase from beet leaves. AB - We have purified to homogeneity 6-Phosphogluconate dehydrogenase from leaves of silver beet (Beta vulgaris L.) by means of cation-exchange and affinity chromatography. The enzyme is a homodimer of 52 kDa subunits; it catalyzes NADP dependent oxidation of 6-P-gluconate with Michaelian substrate saturation. The activity is affected by some intermediates of carbohydrate metabolism, particularly erythrose-4-P. Subcellular fractionation studies indicate the cytosolic location of the enzyme. PMID- 7773203 TI - Significance of the N-terminal fragment of myosin regulatory light chain for myosin-actin interaction. AB - The influence of myosin regulatory light chains (LC2s) lacking the 2kD N-terminal portions of these chains, on internal organization of myosin heads and on actin myosin interaction was studied with limited proteolysis and polarized fluorescence methods. For these studies heavy meromyosin (HMM) preparations were used: HMM containing intact LC2s (phosphorylated or dephosphorylated) and HMM containing LC2s lacking the 2kD N-terminal portions (including serine which can be phosphorylated). It was found that the susceptibility of the heavy chain cleavage site to trypsin and the alkali light chain (LC1) site to papain of myosin containing shortened regulatory LC2s, is not dependent on saturation of LC2s with Ca2+ or Mg2+ ions. This is in contrast to the myosin containing intact LC2s where Ca2+ or Mg2+ ion saturation does demonstrate a dependence. Similarly, in spectroscopic experiments, dephosphorylated HMM containing intact LC2s causes decrease or increase of actin filament flexibility depending on whether Mg2+ or Ca2+ are bound to LC2s. Correspondingly, HMM with shortened LC2s induces only increase of actin flexibility despite cations being bound. We conclude that the N terminal fragment of LC2 is important for ensuring a proper Ca2+ dependent conformation of myosin head in the course of its actin-activated ATP hydrolysis. PMID- 7773205 TI - Role of tumour necrosis factor-alpha in dendritic cell-mediated primary mixed leucocyte reactions. AB - Tumour necrosis factor (TNF alpha) is a major inflammatory cytokine with potentiating effects on specific immune responses, including graft-versus-host disease. This study examined the contribution of TNF alpha to dendritic cell (DC) mediated primary allogeneic T lymphocyte responses. Purified blood DC were shown to produce minimal amounts of TNF alpha mRNA but no significant TNF biological activity or secreted TNF alpha as measured by ELISA. Amplification of DC mRNA by PCR using oligonucleotide primers to CD120a (TNFRI, p55) and CD120b (TNFRII, p75) and probing with specific internal oligonucleotides, suggested that DC express the CD120b but little if any CD120a. These results were confirmed using monoclonal antibodies to the TNF receptors. Polyclonal antiserum specific for TNF alpha blocked the blood DC-stimulated allogeneic mixed leucocyte reaction (MLR). The addition of TNF alpha to suboptimal MLRs (limited DC stimulators), increased the proliferation of responding T lymphocytes. Having confirmed that T lymphocytes produce TNF alpha and express CD120b after stimulation, we sought to clarify whether the contributing effect of TNF alpha to the allogeneic MLR resulted from a TNF alpha-mediated signal stimulating DC activity, or as a result of autocrine stimulation of T lymphocytes. Pre-incubation of DC with TNF alpha did not increase DC stimulatory capacity and late addition of anti-TNF serum (up to 72 h) still had a significant inhibitory effect on the MLR. We conclude that TNF alpha is probably not involved in the initial DC-T lymphocyte interaction, but acts as an autocrine growth factor for DC induced T lymphocyte proliferation. PMID- 7773206 TI - Changes in plasma transforming growth factor beta in response to high-dose chemotherapy for stage II breast cancer: possible implications for the prevention of hepatic veno-occlusive disease and pulmonary drug toxicity. AB - Veno-occlusive disease (VOD) of the liver and pulmonary drug toxicity (PDT) are two major complications of high-dose chemotherapy and autologous bone marrow transplantation (BMT) for solid tumors. We have previously demonstrated that an elevated plasma TGF-beta concentration before transplant predicts the later occurrence of these complications. In the present study, we used a simplified enzyme-linked immunosorbant assay (ELISA) to prospectively evaluate the kinetics of plasma TGF-beta concentrations of 45 patients with stage II breast cancer who underwent high-dose chemotherapy and autologous BMT. We demonstrated that, of the three TGF-beta isoforms, only TGF-beta 1 was present in the plasma. Pre transplant plasma TGF-beta 1 was significantly higher in patients with VOD and PDT compared with that in patients without these complications. The plasma TGF beta 1 level in patients who later developed VOD or PDT decreased to that of controls within 2 days of initiating high-dose chemotherapy; this decrease was not correlated with platelet concentration changes. These results suggest that interventions aimed at preventing the development at VOD or PDT must be given early in the course of high-dose chemotherapy. PMID- 7773204 TI - Nucleotide pool imbalances in the livers of patients with urea cycle disorders associated with increased levels of orotic aciduria. AB - Liver samples obtained at autopsy from patients with ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder that is associated with high levels of orotic acid biosynthesis and excretion were analysed for nucleotide pools. As a control, liver samples from patients with a deficiency of mitochondrial carbamyl phosphate synthetase (CPS-I) which is not associated with increased levels of orotic acidurias were also analysed. The results show that liver tissue from OTC deficiency patients exhibited an increased ratio of uridine nucleotides to adenosine nucleotides, while in CPS-I deficiency patients, no such increase was noted. This study indicates that genetic disorders that are associated with increased loads of orotic acid exhibit abnormally high ratios of uridine to adenosine nucleotides in the liver. This type of imbalance is analogous to that seen in the liver of rats and mice exposed to an orotic acid supplemented or an arginine-deficient diet under liver tumor promoting conditions. It is likely that an imbalance in nucleotide pools may have a significant role in the pathophysiology associated with these disorders. PMID- 7773207 TI - Leukemia-specific allogeneic donor T cells: quantification by limiting dilution assay. AB - Allogeneic T cells are capable of discriminating between leukemia cells and non malignant hematopoetic cells. This has been concluded from clinical BMT data and demonstrated by in vitro experiments. We analyzed the frequency and specificity of leukemia-reactive T cells from syngeneic and allogeneic blood donors by limiting dilution assays for interleukin-2-producing (TH1) and cytotoxic (CTLp) T cells. Target cells were leukemia blasts obtained from a patient with common ALL. Control targets were generated by EBV transformation. Effector cells were generated from the peripheral blood of the patient in remission, from his syngeneic brother and from eight healthy, HLA-mismatched volunteers. The effector cells were stimulated with leukemia cells and interleukin-2. Neither the patient nor his brother were able to generate anti-leukemic CTLp or TH1. The HLA mismatched allogeneic donors displayed anti-leukemic CTLp frequencies with a range from 0 to 68 million. TH1 cells with anti-leukemic specificity were not detectable. We conclude that there are great inter-individual differences in the GVL potential of fully allogeneic peripheral T lymphocytes. It is possible to identify T cell lines with reactivity against leukemia blasts and non-reactivity against normal hematological cells from the same individual. These cell lines are potential effector cells for immunotherapy of human leukemia. PMID- 7773208 TI - Bispecific antibody-mediated cytotoxicity by CD4+ and CD8(+)-activated T cells generated from leukemia patients after allogeneic bone marrow transplantation. AB - The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells. PMID- 7773209 TI - Interleukin-2 activation of chemotherapy and growth factor-mobilized peripheral blood stem cells for generation of cytotoxic effectors. AB - Based on our previous studies demonstrating marked anti-tumor activity of interleukin-2 (IL-2)-activated bone marrow in vitro and in vivo, we studied the generation of anti-tumor cytotoxic effectors from chemotherapy- and growth factor mobilized PBSC from 12 patients with different solid tumors. As chemotherapy and growth factor priming could lead to important qualitative and quantitative alterations of lymphoid cells, we also looked at the distribution of lymphoid cells contained in primed PBSC. In addition, different variables were defined for successful application of the technique to clinical protocols. The cells were placed in culture at varying cell densities in either serum-containing or serum free culture medium, supplemented with IL-2, 100 or 1000 Cetus units/ml at 37 degrees C for 24 or 72 h, in flasks or in culture bags. Anti-tumor cytotoxicity was tested against A375 (melanoma), K562 (CML) and Daudi (Burkitt's lymphoma) cell lines in standard 4 h 51Cr release assay. Marked cytotoxicity was seen against all cell lines tested (A375: 32.7% +/- 5.2; K562: 52.8% +/- 4.8; Daudi: 50.5% +/- 7.2). Cytotoxicity was comparable in serum-containing and serum-free culture conditions and in tissue culture flasks and bags. Cell density up to 10 x 10(6)/ml was not associated with any significant decline in cytotoxicity. IL-2 activation of PBSC after thawing led to the generation of cytotoxicity comparable to that obtained with fresh PBSC. On flow cytometric analysis, the proportion of CD8+ T cells and NK cells (CD56+) was found to be higher in primed PBSC than in control peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773210 TI - Influence of marrow CFU-GM content on engraftment and survival after allogeneic bone marrow transplantation. AB - The influence of the CFU-GM content of donor marrow on the outcome of allogeneic marrow transplantation (BMT) has been debated. We now report 38 patients (25 acute leukemias, 10 chronic myeloid leukemias, two myeloma; 24 in first CR/CP and 14 in more advanced phases of their disease) undergoing unmanipulated HLA identical sibling BMT following conditioning with cyclophosphamide and total body irradiation (TBI). The median number of nucleated cells infused was 4.3 x 10(8)/kg (range 1.5-8.4); median CFU-GM numbers were 2.4 x 10(4)/kg (range 0.1 46). End-points of the study were (1) speed of neutrophil and platelet engraftment; (2) quality of engraftment beyond day +50 after BMT; and (3) transplant-related mortality in patients stratified according to whether they had received less than (n = 18) or more than (n = 20) 2.4 x 10(4)/kg CFU-GM. These two groups were comparable for diagnosis, disease status, donor sex, donor age, recipient sex, recipient age, CVHD prophylaxis, number of cells infused and CMV serology. Neutrophil counts were comparable at all time intervals. There was also no difference in platelet counts on days +7 to +50. However, patients who had received higher CFU-GM numbers had significantly higher platelet counts on day +80 (149 vs. 75 x 10(9)/L; P = 0.002), day +100 (153 vs. 77 x 10(9)/L; P = 0.0009) and day +150 (179 vs. 95 x 10(9)/L; P = 0.01). The 2-year actuarial transplant-related mortality was 5% vs. 53% (P = 0.007) in patients receiving high or low numbers of CFU-GM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773211 TI - Growth and endocrine function following bone marrow transplantation for thalassemia. AB - Twenty two patients with thalassemia major who received successful bone marrow transplantation (BMT) were followed to verify the impact of the transplant procedure on subsequent growth and development. The transplant preparative regimen consisted of busulphan and cyclophosphamide. Growth and endocrinological function were assessed during the first 4 years following BMT. At the time of transplant most patients showed growth retardation. The median difference between chronological age and bone age was -9.5 months for the boys and -8.5 months for the girls. Patients > 7 years old at the time of BMT showed a significant worsening of their growth delay at 48 months following BMT compared with 12 months before transplantation. Patients < 7 years at the time of BMT had their growth retardation constant over time span after transplantation. Moreover six of 11 younger patients showed an improvement of their growth delay compared with one of 11 older patients. The outcome of height standard deviation score at 24 and 48 months following BMT was strictly correlated with the level of serum transaminases and ferritin. Sixteen patients had impaired growth hormone secretion after a provocative test evaluated at 24 months after transplant. At 48 months there was no significant increase in the mean peak GH levels. This study confirms that the growth retardation of patients with thalassemia major is multifactorial. PMID- 7773212 TI - Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR compatible unrelated donors among Japanese. AB - To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan. PMID- 7773213 TI - Engraftment of patients with lymphoid malignancies transplanted with autologous bone marrow, peripheral blood stem cells or both. AB - Forty six patients with lymphoid malignancies receiving autologous transplants using three different sources of hematopoietic stem cells were compared for engraftment parameters. Thirteen patients (five with multiple myeloma, seven with non-Hodgkin's lymphoma and one with Hodgkin's lymphoma) received autologous marrow with post-transplant growth factors (group 1). During the same time interval, 14 patients (five with multiple myeloma, six with non-Hodgkin's lymphoma and three with Hodgkin's lymphoma) were transplanted with autologous marrow plus recombinant granulocyte colony-stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) and post-transplant growth factors (group 2). Nineteen patients (seven with multiple myeloma and 12 with non-Hodgkin's lymphoma) received rhG-CSF mobilized PBSC and post-transplant growth factors (group 3). All PBSC were collected after G-CSF mobilization (16 micrograms/kg/day s.c. for 6 days) without prior chemotherapy. After high-dose myeloablative chemotherapy or chemoradiotherapy, the median days to recovery of neutrophils to levels of 0.5 and 1.0 x 10(9)/l were 12 vs. 9 vs. 9 days (P = 0.0003 (group 1 vs. group 2) and P = 0.53 (group 2 vs. group 3)) and 13 vs. 10 vs. 10 days (P = 0.0003 (group 1 vs. group 2) and 0.92 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively. The median day to platelet transfusion independence was 22 vs. 11 vs. 11 days (P = 0.001 (group 1 vs. group 2) and P = 0.50 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773214 TI - Bone marrow transplant-associated thrombotic microangiopathy: a case series. AB - Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) has been reported with widely varying frequencies and outcomes. Therefore a BMT-TM grading system (0-4) was developed based on the lactate dehydrogenase (LD) level and percentage (%) fragmented cells (FC) as follows: grade 0, normal or increases LD and FC < or = 1.2%; grade 1, normal LD and FC > or = 1.3%; grade 2, increases LD and FC = 1.3-4.8%; grade 3 increases LD and FC = 4.9-9.6%; and grade 4, increases LD and FC > or = 9.7%. Patients with grade 0 and grade 1 BMT-TM did not differ in clinical parameters. Twenty two patients had BMT-TM grade 2-4. These were observed for outcome. Seven of 10 with grade 2 BMT-TM had resolution of BMT-TM a median of 99 days (range 50-229 days) from diagnosis. This occurred spontaneously in five and following discontinuance of cyclosporine (CsA) in two. The remaining three had persistent BMT-TM at grade 2 (two patients) and grade 1 (one patient). In contrast, none with grade 3-4 BMT-TM had resolution. Seven with grades 3-4 BMT TM underwent a variety of plasma exchange procedures; six had partial hematologic responses. Patients with grades 3-4 BMT-TM had a poorer survival (median survival = 60 days) than those with grade 2 BMT-TM where the median survival has not been reached (P = 0.018). These results indicate that BMT-TM is common following allogeneic-BMT and the outcome is dependent on the grade. Those with grade 1-2 BMT-TM generally do well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773215 TI - Case-control analysis of allogeneic bone marrow transplantation versus maintenance chemotherapy for relapsed ALL in children. AB - In a retrospective study, the results of maintenance chemotherapy and allogeneic bone marrow transplantation (BMT) for children who reached a second complete remission (CR2) of their acute lymphoblastic leukemia (ALL) were compared. Case control analysis was performed comparing 25 allogeneic transplant patients (cases) with 97 patients treated with maintenance chemotherapy (controls), who were matched for site of relapse, duration of CR1 and leukemia-free interval from onset of CR2. Until the first relapse, the children were treated according to standard protocols. The majority of patients suffered from a bone marrow relapse, mostly occurring more than 24 months after the onset of CR1. Remission reinduction treatment was heterogeneous. Patients treated with allogeneic BMT received high-dose chemotherapy and total body irradiation prior to BMT. Maintenance chemotherapy in controls was given for approximately 2 years. Following BMT, relapse rate was lower but the treatment-related mortality was higher compared with maintenance chemotherapy, resulting in leukemia-free survival rates at 4 years of 44% and 24%, respectively (not significant, NS). Case-control analysis of leukemia-free survival showed a hazard ratio of 0.756 in favor of BMT compared with chemotherapy (NS). If bone marrow relapses and central nervous system relapses were analyzed separately, a tendency to better leukemia free survival was present after BMT compared with maintenance chemotherapy for patients with a relapse in the central nervous system, but for an isolated bone marrow relapse, no differences in leukemia-free survival were seen between the two groups of patients. PMID- 7773216 TI - Effect of antimicrobial prophylaxis on hematopoietic recovery following autologous bone marrow transplantation: ciprofloxacin versus co-trimoxazole. AB - We evaluated the effect of oral ciprofloxacin on neutrophil recovery in 20 consecutive patients undergoing autologous bone marrow transplantation (BMT) for malignant lymphoma and compared the results with a control group of 20 patients receiving co-trimoxazole and folinic acid. Both groups started the prophylactic antibiotic as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) the day after marrow infusion and continued the former until the onset of febrile neutropenia (median duration of treatment 6 days for co-trimoxazole and 7 days for ciprofloxacin). The time of attain an absolute neutrophil count > or = 0.5 x 10(9)/L was significantly shorter in patients receiving ciprofloxacin (16 days vs 22 days; P = 0.006). There was no difference in time to attain a platelet count > or = 20 x 10(9)/L independent of transfusion or in time to the first febrile episode or incidence of bacteremia. We conclude that antibiotic prophylaxis with ciprofloxacin results in more rapid neutrophil recovery than prophylaxis with co trimoxazole. This may result from a myelosuppressive effect of co-trimoxazole or an enhancement of neutrophil recovery by ciprofloxacin, or both. PMID- 7773218 TI - HLA prediction model for extended family matches. AB - This article derives a probabilistic model for predicting HLA matches from a population of extended family members. (Extended family members are defined as either first cousins or blood-related aunts or uncles). The model uses family pedigree information and haplotype frequency data to estimate the likelihood of a match. Results are given for many ethnic groupings. A case study is also described. This technique is most applicable when all family members are of the same ethnic origin, which increases the likelihood of a match among a small number of family members, and the patient possesses a haplotype having a frequency exceeding 10%, within the patient's ethnic population. Under such conditions, an extended family search can frequently approximate the success rate of a single sibling search. PMID- 7773217 TI - Selective T cell depletion with CD8-conjugated magnetic beads in the prevention of graft-versus-host disease after allogeneic bone marrow transplantation. AB - The effects of a new immunomagnetic method of selectively depleting CD8+ lymphocytes from donor bone marrow were studied in 29 patients undergoing transplantation from HLA-identical sibling (n = 20) or alternative (n = 9) donors. The direct immunomagnetic depletion method consistently removed > 95% of CD8+ cells and the non-specific loss of other cell subsets was only about 15%. Recovery of CFU-GM and BFU-e was on average > 100%. The final graft contained 0.9 +/- 0.6 x 10(8)/kg nucleated cells and 1.4 +/- 2.7 x 10(5)/kg CD8+ cells. Patients also received cyclosporine starting day -1. Engraftment occurred in 28 patients (97%), including three patients who received a non-TBI conditioning regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10(6)/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade > or = II. However, five of eight patients with grafts from alternative donors (63%) had grade > or = II GVHD. Nearly all patients developed fever around day 7, accompanied by fluid overload, mild skin rash and shortness of breath. This syndrome necessitated treatment with steroids. Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depletion. In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplants, but not in transplants from less perfectly matched donors. PMID- 7773220 TI - Lupus inhibitors following bone marrow transplant. AB - Lupus inhibitors have been reported in a number of pathologic states in which there is a disruption of normal immunoregulation. We report here the development of new lupus inhibitors following bone marrow transplantation. Retrospective analysis of 1292 patients undergoing transplantation at the University of Minnesota over a 10 year period demonstrated newly recognized lupus inhibitors in 3% of the patients. These inhibitors were usually detected in the first 1-2 months after transplant. They occurred more frequently in children, with a particularly high incidence in patients with Hurler syndrome. The development of inhibitors was associated with the use of cyclosporine A (CsA) or T depletion for GVHD prophylaxis, with the use of busulfan/cytoxan as a preparative regimen (which includes phenytoin for seizure prophylaxis) and with the occurrence of viral infections. Lupus inhibitors were not associated with development of GVHD, or with any diagnosis other than Hurler syndrome. Thrombotic complications were rare as would be expected in this severely thrombocytopenic population. The incidence of lupus inhibitors that we recognized may substantially underestimate the true incidence as frequent routine coagulation studies were not performed in these patients. Prospective evaluation of lupus inhibitors during bone marrow transplant may provide insight into the pathogenesis of these inhibitors in other disease states. PMID- 7773219 TI - Reversible cyclosporine-induced cortical blindness in allogeneic bone marrow transplant recipients. AB - We report the occurrence of reversible cyclosporine-induced cortical blindness in three allogeneic bone marrow transplant recipients. Possible mechanisms involved in this rare complication, as well as the associated radiographic and pathologic findings, are discussed. PMID- 7773221 TI - Bone marrow transplantation for patients with Fanconi anemia: a study of 24 cases from a single institution. AB - Although bone marrow transplantation (BMT) can eliminate the hematologic manifestations of Fanconi anemia (FA), patients are unusually susceptible to complications associated with the use of cyclophosphamide (CY) in the conditioning regimen. To investigate modifications of the conditioning regimen, we reviewed the records of 24 patients with FA who received an allogeneic BMT. All patients presented with severe pancytopenia. One patient was transplanted with overt leukemia as well. Donors were HLA-identical siblings in 22 cases and 1 and 2-antigen mismatched relatives in two cases, respectively. All conditioning regimens included CY 200 mg/kg in 10 patients; 140 mg/kg with or without antithymocyte globulin in 12 and 20 mg/kg with 400 cGy total body irradiation in two. GVHD prophylaxis comprised methotrexate and/or cyclosporine. Only one of 21 evaluable patients did not show signs of engraftment. Toxicities included grade III/IV mucositis in 20 patients, severe dermatitis in four and veno-occlusive disease in four. Acute GVHD (> or = grade II) occurred in nine of 22 patients. Four patients developed chronic GVHD. With a median follow-up time of 24 months, 14 of the 24 patients are alive with normal hematopoietic function. Eight of the 10 patients with matched sibling donors who were conditioned with CY 140 mg/kg are alive and well. We conclude that BMT is an effective treatment for FA. Conditioning regimens using lower doses of CY are associated with manageable toxicity and can potentially increase the survival rate of patients with HLA matched donors. PMID- 7773222 TI - Allogeneic bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. AB - We studied 23 consecutive patients, median age 34 years, with relapsed or resistant aggressive lymphoma who underwent allogeneic BMT at the UCLA Medical Center Bone Marrow Transplantation Unit from 1 November 1984 to 30 March 1993. All patients were < 50 years of age and had sibling donors who were matched at the HLA-A, B and DR loci. Nine patients had Hodgkin's disease (HD) and 14 had non Hodgkin's lymphoma (NHL); three of these had low grade histology and 11 had intermediate or high grade lymphoma histology. After a median follow-up of 34 months, eight patients are alive, seven without recurrent lymphoma. Five patients had early deaths. The disease-free survival for the entire group is 26% with an overall survival of 29%. There was no difference in survival rate on the basis of disease or histology. Comparing preparative regimens containing TBI to those without there was no difference in survival rate (P = 0.35). Neither age nor sex was a significant determinant of outcome (P = 0.63 and 0.36, respectively). Disease status at the time of transplantation proved to be the important determinant of outcome. Patients transplanted with chemotherapy sensitive disease (n = 9), defined as a partial or complete response to salvage chemotherapy, had a survival rate of 42%, which was significantly better than those who had refractory disease at transplantation (n = 14), who had a survival rate of 21% (P = 0.006). However, this small, but significant fraction of patients with refractory disease was curable. Thus, our data demonstrate that allogeneic bone marrow transplantation is an effective means of treatment for relapsed or aggressive Hodgkin's and non-Hodgkin's lymphoma. PMID- 7773223 TI - Accelerated hematopoietic recovery with the hemoregulatory peptide dimer SK&F 107647 in bone marrow transplantation. AB - The effect of a novel hemoregulatory peptide SK&F107647 on recovery of hematopoiesis was studied in murine bone marrow transplantation (BMT) models. In the first model, lethally irradiated recipient mice were transplanted with 10(6) bone marrow cells from donors given a single injection of either SK&F107647 or PBS 2 days prior to transplantation. The femoral content of GM-CFC was shown to be almost twice as high in mice treated with SK&F107647 compared with controls. Both the marrow GM-CFC progenitor cell population and Mac-1 positive cells in blood were shown to recover faster in recipients of SK&F107647 treated donors. The use of SK&F107647 treated donors did not result in significantly faster blood cell count recovery in the recipient mice. In the second model, lethally irradiated recipients were transplanted with normal bone marrow cells (10(5) 10(6) and then given daily injections of SK&F107647 for 10 days starting 1 day after transplantation. The results show significantly enhanced recovery of GM-CFC in spleen and bone marrow and enhanced numbers of mature Mac-1 positive cells in spleen and peripheral blood. In addition, Thy1.2 positive cells recovered faster in SK&F107647 treated animals compared with controls. The results from these models suggest a role for SK&F107647 in BMT either as a primer of the marrow before transplantation or as an enhancer of hematopoietic recovery when given therapeutically after transplantation. PMID- 7773224 TI - Delayed neutrophil recovery after BEAM chemotherapy and autologous bone marrow transplantation for lymphoma is not associated with increased mortality from infection. AB - Administration of high-dose cytotoxic therapy with autologous bone marrow transplantation (BMT) results in prolonged cytopenia and significant morbidity and mortality. Several groups have reported that the administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with delayed haematological recovery following autologous BMT may accelerate neutrophil recovery and decrease mortality. We have determined the prevalence and natural history of delayed neutrophil recovery following BEAM chemotherapy and autologous BMT for malignant lymphoma in 261 patients treated at a single institution without the use of haemopoietic growth factors. Forty of 261 (15%) patients took > 28 days to reach an absolute neutrophil count (ANC) > 0.5 x 10(9)/L; 29 of these 40 (73%) with delayed engraftment reached an ANC > 0.5 x 10(9)/L by day +42. Five patients with delayed engraftment died before day +100, two of progressive lymphoma, one from unirradiated blood product-related GVHD and two of interstitial pneumonitis (IP). The patients with IP had negative culture and bronchoscopic examinations and onset of assisted ventilation was day +15 and +18, respectively. These results show a high rate of relatively rapid spontaneous recovery in individuals with delayed neutrophil recovery after BEAM plus autologous BMT with a low incidence of death from infection. PMID- 7773225 TI - Treatment of leukemia relapse after bone marrow transplantation with interferon alpha and interleukin 2. AB - A 16-year-old girl with refractory AML received unmanipulated BMT from an unrelated donor. Leukemia relapse occurred 82 days later. The patient was then treated with IL-2 1.8 x 10(6) U/m2 for 5 days per week and 2.5 MU/m2 IFN-alpha three times per week. Toxicities included fever, skin rash, somnolence and a generalized seizure. Treatment was stopped after 2 weeks. Acute GVHD developed at the end of therapy and the patient's leukemia went into remission. She died of fungal pneumonia 30 days later. We conclude that a combination of cytokines may be useful in treating relapsed leukemia after BMT. PMID- 7773226 TI - High-dose melphalan allows durable engraftment of allogeneic bone marrow. AB - Conditioning regimens for allogeneic bone marrow transplantation are designed to eradicate malignant cells and to provide sufficient immunosuppression for engraftment of donor marrow. Total body irradiation and high-dose cyclophosphamide are the most established immunosuppressive agents used for this purpose. It is uncertain whether other alkylating agent-based conditioning regimens are sufficiently immunosuppressive to allow engraftment of allogeneic marrow. We report four patients who had prompt engraftment after conditioning with melphalan-based chemotherapy regimens (BEAM or busulfan/melphalan). Two patients survived without disease for a prolonged period, indicating that these melphalan regimens are sufficiently immunosuppressive to allow sustained engraftment and donor hematopoiesis. PMID- 7773227 TI - Does macrophage colony-stimulating factor have an effect on the mobilisation of peripheral blood stem cells? PMID- 7773228 TI - Rise in IgE levels during acute GVHD is a 'normal' response to increased gut permeability. PMID- 7773230 TI - Bone marrow transplantation for multiple myeloma: the Wayne State experience. PMID- 7773229 TI - Availability of Campath-1 antibodies for bone marrow transplantation. PMID- 7773232 TI - Notifiable diseases annual summary. 1993. PMID- 7773231 TI - Improved method for infusing cells. PMID- 7773233 TI - The immunopathology of chronic inflammatory periodontal disease. AB - Chronic inflammatory periodontal disease is known to be under the control of the immune response. However, the precise mechanism of the immunopathogenesis of this lesion has not yet been fully elucidated. In this review, the regulatory role of both lymphoid and non-lymphoid cells as well as cytokines and accessory molecules in the course of chronic inflammatory periodontal disease is discussed. Finally, based upon previous evidences, an attempt to establish a model of chronic inflammatory periodontal disease is made herein. PMID- 7773234 TI - Strong adjuvant action of Klebsiella O3 lipopolysaccharide and its inhibition of systemic anaphylaxis. AB - Immunization with lipopolysaccharide from Klebsiella O3 as an immunological adjuvant did not cause the death of mice in systemic anaphylaxis to bovine serum albumin. On the other hand, most mice immunized with lipopolysaccharide from Escherichia coli O111, Klebsiella O4 and Salmonella minnesota did die. Klebsiella O3 lipopolysaccharide enhanced IgM and IgG antibody response to BSA more markedly than Escherichia coli O111 lipopolysaccharide, while it affected the production of IgE antibody only slightly. therefore, it is suggested that the inhibition of systemic anaphylaxis by Klebsiella O3 lipopolysaccharide adjuvant might be related to its strong adjuvant action on IgM and IgG class antibody production, and that high levels of circulating IgM and IgG antibodies might act as blocking antibodies in the development of IgE-mediated systemic anaphylaxis. PMID- 7773235 TI - Epidemiological evaluation of Neisseria meningitidis serogroup B by pulsed-field gel electrophoresis. AB - Genomic DNA from 25 strains of serogroup B Neisseria meningitidis was subjected to pulsed-field gel electrophoresis (PFGE) after digestion with Spe I. N. meningitidis genomic DNA displayed considerable diversity. The diversity we observed among these strains was stable and included isolates from an outbreak that were phenotypically identical. This confirms the value of macrorestriction profiling and PFGE in providing epidemiologically stable strain markers for typing meningococci. PMID- 7773236 TI - Studies on adhesion, haemagglutination and other biological properties of Vibrio cholerae O139. AB - The adhesive capabilities of eight Vibrio cholerae O139 epidemic strains to isolated rabbit intestinal epithelial cells (RIEC) were observed to be high similar to those observed with a Vibrio cholerae O1 strain isolated from patients. Toxin production by the strains, measured by accumulation of fluid in rabbit ileal loop model, was high and the toxin was lethal as the animal expired within 6 h. Culture filtrates of the strains exhibited the presence of vascular permeability factor which produce induration and necrosis in the adult rabbit and guinea pig skin. All the strains showed high to moderate haemagglutinin titres against chicken erythrocytes and produced El Tor-like haemolysin. SDS-PAGE of the outer membrane preparation of the strains showed the presence of major protein component at 38 kDa region. The lethality of the toxin, high adhesive activity, shifting of the major outer membrane protein band and production of thermolabile haemolysin on Wagatsuma agar were the major variations of these epidemic strains from V. cholerae O1 and V. cholerae non-O1 strains isolated previously. PMID- 7773237 TI - Detection of attachment of enterotoxigenic Escherichia coli (ETEC) to human small intestinal cells by enzyme immunoassay. AB - Simple immunoassays were developed to study the binding between enterocytes of the small intestine and other cell types, and enterotoxigenic Escherichia coli (ETEC). CFA/I or CFA/II pilus protein or CFA-positive E. coli bacteria were immobilised in wells of microtitre plates and incubated with vesicles or crude mucus prepared from human brush border enterocytes. Binding of the cell preparations was detected by adding specific rabbit anti-brush border IgG followed by urease-labelled goat anti-rabbit IgG and urea substrate. The binding of purified CFA/I to human or rabbit small intestine, human oral epithelial cells or Caco-2 cells was detected with specific anti-CFA/I IgG. Both human brush border and mucus-derived preparations were able to attach to ETEC. The binding was CFA-specific and strong enough to withstand several washings. In contrast, CFA/I did not bind to small intestinal cells of non-human small intestinal origin, indicating that there may be important differences in affinity between receptors present on human small intestinal cells and cells of non-human small intestinal origin. Antibodies directed against human small intestinal and non small intestinal cells did not cross-react with either preparation, indicating that receptors between these different cell sources are different. The EIA proved useful during the identification of a newly-recognised 15 kDa bacterial surface component of ETEC strain H10407P, which may function as a putative attachment factor. The EIAs developed in this study were easy to perform and multiple tests could be performed on small samples, including biopsy samples obtained during endoscopy. PMID- 7773238 TI - Characterization of serogroup A Neisseria meningitidis strains by rRNA gene restriction patterns and PCR: correlation with the results of serotyping, subtyping and multilocus enzyme electrophoresis. AB - We studied 35 strains of Neisseria meningitidis serogroup A from different locations (France, Central African Republic, Sudan and Burkina Faso) using both ribotyping and a polymerase chain reaction (PCR). A non-radioactive probe label was used for ribotyping; detection consisted of an immunoenzymatic procedure using a bispecific antibody. The PCR was designed to amplify the 16S-23S rDNA internal transcribed spacer. These techniques were compared with other markers. The strains were identified as belonging to three clones (I, III-1, IV) by multilocus enzyme electrophoresis (MEE) and to three subtypes by serological methods. Ribotyping identified five groups and PCR identified four groups. Ribotyping gave more diversity between strains than either MEE or sero/subtyping, but confirmed the epidemiological data provided by the combination of these two techniques. The PCR provided a simple and convenient one-step procedure for the differentiation of strains of serogroup A. PMID- 7773239 TI - Immunosuppression induced by Salmonella infection is correlated with augmentation of interleukin-2 receptor alpha chain expression in murine splenic lymphocytes. AB - In a previous study, we observed that the suppression of T-cell proliferation induced by Salmonella cell-free extract was associated with augmentation of IL-2 receptor (IL-2R) alpha chain expression. In this study, we also observed this kind of augmentation of IL-2R alpha in Salmonella-infected mice. Phytohaemagglutinin (PHA)-stimulated proliferation of murine spleen cells was significantly suppressed when the mice were infected with Salmonella typhimurium. However, expression of the alpha chain but not the beta chain of IL-2R in lymphocytes was augmented by the infection. Analysis of the IL-2R-positive cell population showed that the augmentation of IL-2R alpha was not specific to certain cell subpopulations. Furthermore, the inhibition of PHA-stimulated murine spleen cell proliferation and the augmentation of IL-2R alpha expression induced by the infection in lymphocytes was completely reversed by treatment with anti interferon-gamma monoclonal antibody (anti-IFN-gamma Ab). These results suggest that the suppression of T-cell proliferation induced by Salmonella infection was associated with augmentation of IL-2R alpha expression in an IFN-gamma production dependent manner in the same way as the suppression of T-cell proliferation induced by Salmonella cell-free extract. PMID- 7773240 TI - Enhanced cellular response in mice treated with a Brucella antigen-liposome mixture. AB - The capacity of liposomes constituted by dycetyl-phosphate (0.009 mM), cholesterol (0.017 mM), lecithin (0.003 mM), and myristic (0.1 mM), stearic (0.1 mM), or oleic acid (0.1 mM) to modify the lymphocyte response to Brucella melitensis antigens in mice was studied. Mice treated with antigens mixed with liposomes containing myristic, stearic or oleic acid had higher antibody titres than mice given antigen suspended in a saline solution. Liposomes alone, without Brucella antigens, resulted in increased 3H-thymidine incorporation by lymphocytes both in vivo and in vitro. The addition of polyclonal activators (LPS and ConA) caused a further increase of 3H-thymidine uptake. Moreover, spleen lymphocytes from mice inoculated with Brucella antigens mixed with the liposomes had a significantly lower population of B lymphocytes (10%), and a notable increase in the Tc lymphocytes (20%). Autoradiography of sections of popliteal ganglia of treated mice showed that the radioactivity was concentrated mainly in the membrane structures of the cell. PMID- 7773241 TI - Rapid detection of Salmonella subspecies I by PCR combined with non-radioactive hybridisation using covalently immobilised oligonucleotide on a microplate. AB - A polymerase chain reaction (PCR)-based test was developed for the detection of Salmonella. One pair of oligonucleotide primers was designed to amplify a 93-bp fragment of a gene required for the invasion of HeLa cells by Salmonella ser Typhi strain Ty2. The amplified product was analysed by non-radioactive sandwich hybridisation in microtiter plates using two oligonucleotides. The capture oligonucleotide was covalently linked onto animated wells of microtiter plates. The detection oligonucleotide was labelled with biotine. The hybrid molecules were detected by avidine conjugated with alkaline phosphatase and chromogenic substrate. The described combination of microplate sandwich hybridisation and PCR seems to be a suitable method for rapid detection of Salmonella subspecies I. It only requires a thermal cycler and a conventional microtiter reader, and can be readily done on a large scale. PMID- 7773242 TI - Potential animal models of Helicobacter pylori infection in immunological and vaccine research. AB - Presence of Helicobacter pylori in the human gastric mucosa is associated with chronic gastritis and promotes the formation of peptic ulceration. Furthermore, long-term gastritis caused by the bacteria represents an increased risk of developing gastric cancer. Much controversy remains about the pathogenic mechanisms by which H. pylori can induce disease because of the limitations of animal models and the relevance of in vitro observations to the in vivo disease process. Studies of putative pathogenic factors such as induction of inflammatory mediators and immune evasion are required to understand how to design a vaccine against the infection. Vaccine adjuvants, delivery systems and therapeutic vaccination are likely to be the areas of major progress in the future. Data related to immunological aspects and vaccine development in potential animal models are reviewed. PMID- 7773243 TI - Cell surface characteristics of Helicobacter pylori. AB - Helicobacter pylori is an important gastroduodenal pathogen of humans. Immunological and structural studies have been performed on the phospholipids, lipopolysaccharides (LPS) and some surface proteins of H. pylori strains. H. pylori LPS has, in general, low immunological activity and this property may aid the survival of this chronic infection. Nevertheless, H. pylori LPS has been found to influence the quality of gastric mucin and to stimulate pepsinogen secretion, thereby contributing to gastric disease. A number of putative adhesins of the bacterium have been described. This multiplicity of adhesins may reflect that H. pylori adherence is a multi-step process involving different interactions, and that different adhesins may mediate adherence to various sites in gastric tissue. PMID- 7773245 TI - Isotypic analysis of specific antibody response in serum, saliva, gastric and rectal homogenates of Helicobacter pylori-infected patients. AB - The relationship between systemic and local humoral immune response to Helicobacter pylori is poorly understood. To further address this issue we measured, using ELISA, H. pylori-specific IgG and IgA antibodies in serum, saliva, gastric and rectal homogenates of H. pylori-infected patients. A total of 107 patients who underwent upper GI endoscopy and/or sigmoidoscopy were studied. The isotypic pattern of H. pylori-specific antibodies appeared to differ at the serum, salivary, gastric and rectal mucosa level. Serum H. pylori IgG titers were higher than those of the serum-specific IgA. On the contrary, in saliva samples H. pylori IgA titers were higher than specific IgG titers. In gastric homogenates, specific IgG and IgA titers were similar. H. pylori-specific IgG were detectable in rectal homogenates but no or very low H. pylori-specific IgA were found in the same material. Furthermore, no difference was found in H. pylori IgG and IgA in serum, saliva and gastric homogenates between duodenal ulcer and non-ulcer dyspepsia patients. Data of the present study indicate that, in H. pylori-infected patients, the specific immune response is as follows: (1) it involves the secretory immune system; (2) it is paralleled by the specific salivary IgA; (3) it does not differentiate duodenal ulcer from non-ulcer dyspepsia patients; and (4) it does not take place in the large bowel. PMID- 7773244 TI - Salivary specific IgG is a sensitive indicator of the humoral immune response to Helicobacter pylori. AB - In humans, salivary antibodies are secreted during humoral immune response. Helicobacter pylori infection is associated with systemic humoral immune response reflected by raised serum levels of specific IgG. The present study was aimed at exploring whether salivary concentrations of specific H. pylori IgG are a reliable indicator of H. pylori infection. Serum and salivary samples were obtained from 291 subjects attending the GI clinic and tested for H. pylori specific IgG by a direct ELISA (94% sensitivity, 95% specificity for serum determinations) using a crude H. pylori sonicate as antigen. Data are given as optical density (mean +/- S.D.). Levels of salivary H. pylori IgG paralleled those of circulating specific IgG in the 291 subjects studied (0.981 +/- 0.431 vs. 0.777 +/- 0.682, respectively). A significant positive correlation was found between specific H. pylori IgG in sera and saliva samples (r = 0.981, P < 0.0001). An overall concordance between circulating and salivary H. pylori IgG was observed in 238 out of the 291 (81.7%) subjects. Salivary H. pylori IgG represent a sensitive marker of specific humoral immune response and they may substitute circulating H. pylori IgG measurement when sera samples are not available. PMID- 7773246 TI - Investigation of Helicobacter pylori ascorbic acid oxidating activity. AB - Helicobacter pylori sonicate was shown to oxidize ascorbic acid. Ascorbic acid oxidation was determined by chromatography combined with electrochemical detection. Water soluble ascorbic acid oxidase activity was rather independent of pH with a pH optimum around 2. By gel filtration the oxidizing activity co-eluted with an absorbency peak at 408 nm. The relative molecular mass (Mr) was approximately 14,000. It is suggested that this oxidating activity was caused by a cytochrome c-like molecule. Ascorbic acid oxidating activity could also be extracted from bacterial membranes by detergents. Gel filtration showed several forms, the major one with a Mr = 19,000. pH optimum was 6-7. Other oxidase positive bacterial strains like Campylobacter coli, Enterobacter cloacae and Pseudomonas aeruginosa could degrade ascorbic acid. Since ascorbic acid oxidation by Helicobacter pylori whole bacterial lysates has a pH optimum in the acidic range corresponding to pH in gastric fluid, the activity of the cytochrome c-like water soluble oxidant of Helicobacter pylori seems to be primarily important for the destruction of ascorbic acid in the gastric juice of infected patients. PMID- 7773247 TI - HLA-DR expression on CD8 lymphocytes from gastric mucosa in urease-positive and urease-negative gastritis. AB - We isolated lymphocytes from chronically inflamed gastric mucosa. We analysed the expression of IL-2 receptors (CD25), transferin receptors (CD71) and HLA-DR molecules on T lymphocytes by flow cytometric analysis in 16 patients with urease positive and in 7 patients with urease-negative chronic gastritis. In G0, G1 and G2 histological type (Sydney classification) of gastritis the number of lymphocytes obtained from the gastric mucosa biopsies was too low for the flow cytometric analysis. However, in G3 histological type of chronic gastritis we obtained enough cells for the flow cytometric analysis in 75%. We demonstrated a significant increase in HLA-DR expression on CD8 cells from patients with urease positive gastritis compared to urease-negative gastritis. We also observed a statistically non-significant increase in HLA-DR expression on CD3 cells, and in CD71 expression on both CD3 and CD8 cells in urease-positive gastritis. However, no difference in CD25 expression was found between the two types of gastritis. PMID- 7773248 TI - Attachment, ingestion and intracellular killing of Helicobacter pylori by human peripheral blood mononuclear leukocytes and mouse peritoneal inflammatory macrophages. AB - The different steps of phagocytosis, attachment, ingestion and intracellular killing of cells of Helicobacter pylori strain 17874 (expressing sialic acid specific haemagglutinin) and cells of H. pylori strain 17875 (expressing non sialic acid-specific haemagglutinin) have been studied. More cells of sialopositive H. pylori strain 17874 have been found attached to human peripheral blood mononuclear leukocytes (PBM) and mouse peritoneal inflammatory macrophages (PIM) than cells of sialonegative H. pylori strain 17875. Binding of cells of H. pylori strain 17874 has been significantly inhibited by treatment of phagocytes with neuraminidase. Inhibition of adhesion of these bacteria preincubated with foetuin to normal phagocytic cells has also been found. Well adhering cells of H. pylori strain 17874 were more resistant to killing mechanisms of human PBM and mouse PIM than cells of strain 17875. Good, probably sialic acid-specific haemagglutinin dependent, adhesion of H. pylori bacteria to phagocytes can be considered as an important virulence factor which facilitates the pathogen to avoid the defence mechanisms. PMID- 7773249 TI - Molecular analysis of Helicobacter pylori populations in antral biopsies from individual patients using randomly amplified polymorphic DNA (RAPD) fingerprinting. AB - In the present study, randomly amplified polymorphic DNA (RAPD) fingerprinting has been used to analyse multiple single colony isolates of Helicobacter pylori from antral biopsies in an attempt to ascertain whether or not multiple strains are present in individual patients using single biopsy samples. The RAPD fingerprints derived from single colonies obtained from the same biopsy specimen were in all cases indistinguishable. The previously noted heterogeneity between H. pylori strains from different individuals was confirmed. RAPD fingerprinting, combined with a simple method of template preparation, was shown to be an excellent method for H. pylori strain differentiation. The results of this study indicate that the H. pylori population is homogeneous in individual patients at a single gastric site. PMID- 7773250 TI - Development of a PCR-based technique for detection of Helicobacter pylori. AB - A primer-set was designed for specific detection of genes that encode for 16S rRNA of Helicobacter pylori, using direct polymerase chain reaction (PCR). The primers were selected in the hypervariable regions, derived from a complete small subunit 16S rRNA sequence of the reference strain H. pylori CCUG 17874. The primer-set amplified a 537 base pair (bp) sequence specifically from chromosomal H. pylori DNA. Amplification of purified chromosomal H. pylori DNA was achieved at concentrations as low as 1 femto gram (fg), equivalent to 5 bacteria. Furthermore, as few as 1 lysed H. pylori cell was detected by this PCR technique. The specificity of the primers was 100%, since purified chromosomal DNA was detected from all 32 various H. pylori isolates, whereas no other bacteria species were detected, whether related to Helicobacter or not. The 16S rDNA primers successfully detected H. pylori in antral biopsy specimens collected from infected patients. PMID- 7773251 TI - Gastric juice neopterin in Helicobacter pylori infection. AB - Neopterin, a pteridine compound produced by macrophages activated by interferon gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori, a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 +/- 15.6 vs. 2.1 +/- 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 +/- 12.0 vs. 11.1 +/- 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 +/- 3.2 vs. 1.3 +/- 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 +/- 4.6 vs 1.6 +/- 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux. PMID- 7773252 TI - Glutathione S-transferases in housefly (Musca domestica): location of GST-1 and GST-2 families. AB - The two families of dipteran glutathione S-transferases (GST-1 and GST-2) were located separately by immunohistology on sections of adult houseflies. GST-1 was distributed in haemolymph cells, whereas GST-2 was found in the indirect flight muscles of the thorax and in the central nervous system. In the muscles, the distribution of GST-2 seemed to be uniform in cells, whereas in the brain and the thoracic ganglia GST-2 was found mainly in the cortical areas which are made up by cell bodies. Comparison of the GSTs' location between an insecticide susceptible strain of housefly and resistant ones indicated no variation due to resistance. Enzyme-linked immunosorbent assay tests were used to dose GST-2. In houseflies, there were 60 pmol of GST-2/fly, 80-90% being found in the thorax, about 10% in the head and the remainder in the abdomen. Furthermore, the roles of these GSTs are discussed in relation to their location and our knowledge on their catalytic activities or their transport ability in invertebrates and mammals. PMID- 7773253 TI - Primary structure of proteins from the wing cuticle of the migratory locust, Locusta migratoria. AB - Wing cuticle from pharate adult locusts, Locusta migratoria, contains several prominent proteins which occur as minor components or are completely absent in other cuticular regions. Six of the wing-specific proteins have been purified and their amino acid sequences determined by combined use of mass spectrometry and automated Edman degradation. During the sequence determination very long sequence runs (90-121 residues) were necessary in order to establish the primary structure. All the wing-specific cuticular proteins from locusts contain the repeated short sequence motif -Ala-Ala-Pro-Ala/Val-, which is common for all hitherto sequenced cuticular proteins from pharate locusts. Several of the wing specific proteins also possess an N-terminal region rich in glycine, tyrosine and leucine, characteristic for many locust cuticular proteins. Two of the analysed proteins have a conserved 61-residue sequence in common with a previously sequenced protein from locust wing cuticle and with two proteins from the pharate cuticle of adult Tenebrio molitor. Possible roles for the various sequence motifs are discussed. PMID- 7773254 TI - Characterization of a new class of transcribed repetitive DNA sequence which also exists as a hybrid with HP1 mRNA; potential for site-specific recombination in Drosophila melanogaster. AB - A new class of dispersed repetitive DNA designated as vivi-sequence (VS) has been identified in Drosophila. It is relatively AT rich and is transcribed. The VS transcription is developmentally regulated and generates multiple transcripts. A hybrid transcript, designated fl-cDNA, has been identified in which a small segment of the VS is fused to the 5' end of an unrelated structural gene transcript coding for the heterochromatin protein HP1. The VS has recombination signal sequences (RSS) characteristic of vertebrate immunoglobulin genes. Such sequences are also present in the HP1 DNA. In both cases the recombination signal sequences are found close to the junction between HP1 and the VS in fl-cDNA. There is additional sequence identity both 5' and 3' of the junction between HP1 and the VS in fl-cDNA. We propose that (a) the HP1-VS composite transcript represented by the fl-cDNA may be the product of recombination between the two sequences, (b) that the process is mediated by the RSS and/or the DNA downstream of the junction between HP1 and the VS and (c) that the recombination event may lead to the inactivation of the HP1 gene in a cell and tissue specific manner. PMID- 7773255 TI - Expression cloning and characterization of a pupal cuticle protein cDNA of Galleria mellonella L. AB - Epidermal mRNA of freshly ecdysed pupae of Galleria mellonella was used to establish a cDNA library in phage lambda gt11. A cDNA clone was isolated by means of a pupal cuticle protein (PCP) specific antibody. Nucleic acid sequence data show an insert of 1212 bp with an open reading frame of 1062 bp. The presence of start, stop, and polyadenylation sites suggests, that this insert represents a full length transcript. Conceptual translation resulted in a protein of 353 amino acids including a signal peptide. The final processed protein product is rich in alanine and charged amino acids like glutamic acid. It has a calculated pI of 4.19 and a molecular mass of 34.272 kDa. In hybrid selection/in vitro translation and in vitro transcription/translation experiments a translational product of 54 kDa was synthesized. The difference between apparent and calculated molecular mass is thought to be due to the relatively high amount of glutamic acid residues clustered in two regions. The developmental profile of expression of the corresponding gene was analyzed by northern blot hybridization using a cDNA probe. The time course of expression is coincident with developmentally regulated metamorphic changes in the integument. PMID- 7773256 TI - Characterization of a Bombyx mori cDNA encoding a novel member of the attacin family of insect antibacterial proteins. AB - A Bombyx mori cDNA was cloned that hybridized with Hyalophora cecropia attacin probe and its nucleotide sequence was determined. This cDNA consisted of 846 nucleotides and the deduced amino acid sequence showed that the cDNA encodes an attacin precursor protein. The putative mature protein of B. mori attacin had 70.4, 68.3 and 18.8% identity in amino acid sequences with that of H. cecropia acidic and basic attacins and Sarcophaga peregrina sarcotoxin IIA, respectively. B. mori and H. cecropia attacins and S. peregrina sarcotoxin IIA had two subdomains in each G domain, suggesting that common amino acid residues in the subdomains are conserved during evolution and plays an important role in the activity of the antibacterial proteins. Expression of B. mori attacin gene was rapidly induced by the injection of Escherichia coli cells into B. mori larvae and continued at least for 48 h mainly in fat bodies and hemocytes. PMID- 7773257 TI - The B proteins secreted by the tubular accessory sex glands of the male mealworm beetle, Tenebrio molitor, have sequence similarity to moth pheromone-binding proteins. AB - B proteins represent one of the four major protein groups secreted by the tubular accessory glands of adult, male mealworm beetles. They are acidic proteins with an apparent molecular mass of 18.8 kDa. In this paper we present the deduced amino-acid sequences of two, almost identical B proteins, termed B1 and B2. The mature proteins are 118 amino acids long. They contain 11 (B2) or 12 (B1) possible phosphorylation sites and are rich in glutamic acid (16%). Lectin binding experiments indicate the presence of asparagine linked carbohydrate. The secondary structure of the B proteins is predicted to be almost completely alpha helical. The B proteins show significant sequence resemblance to a group of pheromone- and odorant-binding proteins in moths and Drosophila, suggesting a role as carrier proteins for lipids. PMID- 7773258 TI - Incidence of laxative abuse in community and bulimic populations: a descriptive review. AB - Estimates of the incidence of laxative abuse in bulimics and in the community-at large vary widely for various population samples. This review identified 73 studies in which laxative abuse could be assessed in bulimics, nonbulimics, and the community-at-large. Relative risk values for laxative abuse among population subsamples were estimated by moment methods statistical procedure based on mixed model analysis. Results indicated that the lifetime occurrence for laxative abuse behavior in the community-at-large was 4.18%. Bulimic behavior increased the risk for laxative abuse 3.57-fold to 14.94%. Several methodologic and population parameter characteristics are examined for their select impact on laxative abuse. Review of medical nomenclature for classifying laxative substances, iatragenic effects of laxative abuse, and assessment recommendations are also included. PMID- 7773259 TI - The theme of death in the French and German literature on eating disorders. AB - It is not widely appreciated in the English-speaking world that a number of articles written in French and German do address the role played by death preoccupations and concerns in the development and maintenance of eating disorders, particularly anorexia nervosa. In previous published articles these important "hidden" threads have been highlighted in examining in some detail, the writings of the German authors Binswanger, Von Weizsacker, and Thoma. In this article, the writings of other German authors are also briefly reviewed as well as the French authors Bensoussan, Fouraste, Raimbault, and Thouzery-Loras. Implications and issues are posed for both the researchers and clinicians alike contributing to the literature in English on eating disorders, who do not necessarily embrace these themes in therapy and who may not reflect their significance to theory in the literature itself. PMID- 7773260 TI - Anorexia nervosa: directions for future research. Study Group on Anorexia Nervosa. AB - On September 27-29, 1993, the Study Group on Anorexia Nervosa (AN): Basic Mechanisms, Clinical Approaches and Treatment met in Geneva, Switzerland to discuss recent progress in research on anorexia nervosa, and to identify directions for future studies. Anorexia nervosa is a disorder of unknown etiology, without a specific curative treatment, affecting mostly individuals in adolescence and early adulthood, with significant morbidity and mortality, and having a major impact on psychosocial and vocational development. In anorexia nervosa there are severe disturbances in virtually every endocrine system, such as the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary gonadal (HPG) axis, the hypothalamic-pituitary-thyroid (HPT) axis, the growth hormone (GH)/somatomedin C (IGF-1) system, and the central and peripheral arginine vasopressin (AVP) systems. Furthermore, classical neurotransmitter systems, such as the cholinergic noradrenergic, and serotonergic systems, are abnormally regulated in anorexia nervosa. New research data is also emerging on the abnormal regulation of immune function in this disorder. The Study Group concluded that even though several biological systems are abnormally regulated in anorexia nervosa, there is no biological test which is specific enough to make the diagnosis of the disorder. New directions for research in anorexia nervosa are identified and discussed in this report. Finally, the Study Group proposed future meetings to bring together clinical and pre-clinical (pharmacological, biochemical, and molecular) scientists studying topics, such as neuroendocrine function, which are important in the biology of anorexia nervosa. PMID- 7773261 TI - Clinical characteristics of eating disorder patients who report sexual or physical abuse. AB - At initial contact in an eating disorders clinic, 712 female eating disorder patients were asked if they had been physically or sexually abused as children. They also completed a Beck Depression Inventory (BDI) and an Eating Disorders Inventory (EDI). Their eating disorder symptom frequency and severity was determined. They were asked if they had alcohol problems, had attempted suicide, or had shoplifting problems. Twenty-nine percent reported sexual abuse. Twenty five percent reported physical abuse. There was no correlation between reports of abuse and symptom frequency or severity. The abused subjects were more depressed on the BDI and showed more psychological disturbance on the EDI. Abused subjects were much more likely than nonabused subjects to report alcohol problems, suicide attempts, or shoplifting. PMID- 7773262 TI - Temperament in eating disorders. AB - This study examined dimensional personality and temperamental characteristics in women with eating disorders. Clinical symptoms, personality, and temperament were examined in 30 women with anorexia nervosa (AN), 32 women with bulimia nervosa with no history of anorexia nervosa (BN), and 20 women with comorbid anorexia and bulimia nervosa (AB). Temperament differed markedly across the groups on the Tridimensional Personality Questionnaire (TPQ) with AN women showing greater reward dependence, BN women scoring higher on novelty seeking subscales, and AB women showing high harm avoidance. The TPQ subscales also displayed higher classification accuracy than other personality and symptom measures. Temperamental features are distinct across eating disorder subtypes. Temperament could reflect differential vulnerabilities for the development of specific eating disorder symptom clusters. PMID- 7773263 TI - Psychological correlates of weight fluctuation. AB - This investigation attempted to determine psychological correlates of weight fluctuation in a sample of 497 normal weight and obese adults who were enrolled in a prospective, natural history study. Subjects were stratified by gender, obesity, and age and classified as weight maintainers, gainers, or losers based on their changes in weight over a 1-year period. Subjects were further classified as either weight fluctuators or nonfluctuators based on historical self-report. Nonfluctuators reported significantly higher general well-being, greater eating self-efficacy, and lower stress than weight fluctuators, regardless of body weight. Weight maintainers had more favorable eating self-efficacy related to negative affect than weight gainers. Results suggest that weight fluctuation is strongly associated with negative psychological attributes in both normal weight and obese individuals. Future research should focus on the assessment and treatment of weight fluctuation and on weight maintenance, irrespective of weight status. PMID- 7773264 TI - Developmental role of perceived parental control in the eating psychopathology of Asian and Caucasian schoolgirls. AB - It has been suggested that the relatively high levels of eating psychopathology among Asian schoolgirls living in the United Kingdom are due to "culture clash," but this construct needs further definition. A recent study has shown that perceived control by family members is important in determining the relatively unhealthy eating attitudes of Asian adolescents. However, that study focused on older adolescents (aged 14-15 years). The present study examines the development of that effect in a sample of Asian and Caucasian adolescent girls with a broader range of ages (aged 12-16 years). Again, the unhealthy eating attitudes of Asian girls were partly explained by their high levels of perceived maternal control. However, this effect was particularly strong among the older girls, suggesting a developmental trend through adolescence. There might be clinical benefits of addressing perceived or actual maternal control in these girls. PMID- 7773265 TI - Female adolescents of alcohol misusers: disordered eating features. AB - Studies show that children of alcohol-abusing parents constitute an at-risk population. This study attempted to understand the impact of parental alcohol misuse on the disordered eating behaviors of their female adolescent children, based on a sample of 532 teenagers from alcohol-misusing parents in Minnesota. These female adolescents had significantly higher prevalence rates of all the seven eating disordered symptoms that were studied. The study also identified a few protective factors: Those who did not develop any of the disordered eating symptoms were more satisfied with their present weight. Further, they worried less about abuse from parents and perceived that their school personnel cared about them. PMID- 7773267 TI - In defense of psychosomatic theory: a critical analysis of Allison and Heshka's critical analysis. AB - This article analyses Allison and Heshka's (Internal Journal of Eating Disorders, 13, 289-295, 1993.) critical analysis of studies supporting psychosomatic theory. Questionned first is, Allison and Heshka's contention that the obese overreport emotional eating as a result of effects of demand characteristics, social desirability, and interpersonal expectancies. These effects, however, indicate that a more plausible response would be an underreport of emotional eating. Also addressed is Allison and Heshka's (Eating Disorders: The Journal of Treatment and Prevention, 1, 31-38, 1993.) contention that a high correlation between a measurement instrument and a measure of social desirability invalidates that measurement instrument. Finally, in a rebuttal of Allison and Heshka's critical analysis of studies supporting psychosomatic theory, it is elaborated why emotional eating explains so little variance in weight gain and obesity. PMID- 7773266 TI - Premorbid onset of psychopathology in long-term recovered anorexia nervosa. AB - It is recognized that patients with anorexia nervosa commonly have other psychiatric illnesses. No study, to our knowledge, has determined whether these other psychiatric disorders occur prior to the age of onset of anorexia nervosa. We obtained a retrospective history from 24 subjects who were long term (more than 1 year) recovered from anorexia nervosa. We found that 58% reported that they had the onset of one or more childhood anxiety disorder diagnoses at the age of 10 +/- 5 years old. This was 5 years before the mean age of onset of anorexia nervosa. The onset of depression was about 1 year before the onset of anorexia nervosa in about one half the subjects. Alcohol and substance abuse/dependency tended to occur after the onset of anorexia nervosa and only occurred in anorexic subjects who binged and/or purged. The early and common onset of childhood anxiety disorders in a substantial percentage of anorexics raises the possibility that childhood anxiety disorders herald the first behavioral expression of a biologic vulnerability in some subjects who develop anorexia nervosa. PMID- 7773268 TI - Early trauma, dissociation, and late onset in the eating disorders. AB - Although the majority of patients with anorexia nervosa and bulimia nervosa develop these disorders in their teens and 20s, some patients develop an eating disorder in their 30s, 40s, or 50s. We present a subgroup of patients with the following pattern of symptoms and historical detail: (1) severe sexual and physical abuse by family members; (2) relatively good premorbid professional and marital adjustment (considering later difficulties) though characterized by (3) hypomania, binge eating, and morbid obesity. A pronounced shift in eating behaviors follows (4) medical trauma (e.g., injury, cancer, surgery) that occurs after age 30, interrupts previous hypomanic adaptation, and leads to severe restriction, purging, and dramatic weight loss (e.g., 100 lb). Although only one patient met full criteria for anorexia nervosa, weight loss and starvation were serious enough to provoke further medical crises in all patients. Finally, (5) during both weight loss and weight restoration patients demonstrated significant dissociative disturbance, including dissociated mood and personality states (i.e., multiple personality disorder), self-destructive behavioral episodes repeating early trauma, and avoidance of food as a way to manage PTSD symptoms. PMID- 7773269 TI - Pictorial adaptation of Stroop measures of body-related concerns in eating disorders. AB - Patients with eating disorders were asked to color-name pictures of a variety of body shapes. The time taken to color-name these stimuli was compared with the time taken to color-name a series of neutral visual stimuli. There was a significant delay in naming body shapes in comparison to neutral stimuli, and this delay was greater in anorexic and bulimic patients than in controls. Previous Stroop adaptations have used verbal stimuli to assess the intensity of weight and shape-related concerns. The possible advantages of pictorial stimuli are discussed. PMID- 7773270 TI - The effect of mobilization on cervical headaches. AB - Headaches of cervical origin are often treated with mobilization. Mobilization of the upper cervical spine, occiput-C3, and effect on frequency, duration, and intensity of cervical headaches were studied utilizing an A-B-A single case design. Ten subjects who met the operational criteria of cervical headaches completed the study. A headache log was used to document headache frequency, duration, and intensity throughout all three phases (A-B-A). The baseline phase (A) lasted approximately 1 month, and no intervention was performed. The intervention phase (B) consisted of 9-12 treatment sessions, two times per week for 3-4 weeks. Visual analysis of data plots revealed a decrease in headache frequency, duration, and intensity from the baseline phase to the treatment phase. This improvement continued through the second A phase for frequency but leveled off for both duration and intensity. A one-way analysis of variance supported the findings from the visual analysis. In these 10 subjects, mobilization had a therapeutic effect on cervical headaches. PMID- 7773271 TI - The ankle ligaments: consideration of syndesmotic injury and implications for rehabilitation. AB - Injury to the distal tibiofibular syndesmosis (DTFS) may be more common than previously reported. This injury is typically caused by external forces which produce sudden ankle dorsiflexion or plantar flexion in combination with external rotation of the foot. Common mechanisms include direct contact with another player or uneven physical terrain. Improper diagnosis of this injury may greatly delay the return to normal functional status and promote the development of chronic instability, degenerative joint changes, and pain. The purpose of this clinical commentary is to review the ligamentous anatomy of the ankle and the incidence of injury to the lateral ligaments of the ankle, with emphasis on DTFS injury. Special tests which enhance the recognition of DTFS injury, such as the external rotation stress test and the distal tibiofibular compression test, and a rehabilitation progression are presented. PMID- 7773273 TI - A modified internal rotation stretching technique for overhand and throwing athletes. AB - Strength, stretching, and rehabilitation methods for the shoulder have been previously described and have been universally applied; nevertheless, many throwing athletes continue to develop overuse injuries. The pitching process tends to increase external rotation and limit internal rotation of the shoulder joint. Our technique involves a modified stretching method of the posterior shoulder musculature. The athlete lies prone with the elbow flexed 90 degrees. With the shoulder abducted 90 degrees, in neutral flexion/extension, and 90 degrees or more of internal rotation, the scapula protrudes posteriorly. By depressing the inferior angle of the scapula toward the thoracic wall, the infraspinatus muscle and posterior joint capsule are effectively isolated and stretched. Manual stabilization of the scapula onto the chest wall transfers the internal rotation movements to the glenohumeral joint, as opposed to sharing the movement with the scapulothoracic articulation. This method improves the efficacy of the internal rotation stretching exercise for the glenohumeral joint. Such an addition to traditional stretching methods may increase the efficiency of the least effective component. We conclude that this modification to traditional programs should be an integral part of the training and rehabilitation program of any athlete requiring near maximal performance of the shoulder. PMID- 7773272 TI - The contributions of proprioceptive deficits, muscle function, and anatomic laxity to functional instability of the ankle. AB - Functional instability is a common complication following an acute ankle sprain. Three potential contributing factors underlying the ankle which chronically gives way are proprioceptive deficits, muscle weakness, and ligamentous laxity. This study's purpose was to document the presence or absence of these concerns in a sample of subjects with unilateral functional ankle instability. Both ankles of 42 subjects were randomly assessed for passive movement sense into inversion and generation of peak torque by the evertors isokinetically. Thirty-four subjects were available for documentation of talar tilt of both ankles through inversion stress radiographs. Analysis found significantly greater mean values for passive movement sense and talar tilt for the involved ankles compared with the uninvolved, while no significant strength differences in peak torque of the evertors were present. Fifty-eight percent of the sample demonstrated clinical impairments in at least one of these three categories. In conclusion, deficits in passive movement sense and anatomic stability are greater concerns than strength deficits when managing the ankle with functional instability. PMID- 7773274 TI - Shoulder kinesthesia in healthy unilateral athletes participating in upper extremity sports. AB - Shoulder kinesthesia has not been extensively studied in upper extremity athletes. The purpose of this study was to determine if there were differences in threshold to detection of passive motion between dominant and nondominant shoulders of healthy overhead athletes in two positions, 0 degrees and 75 degrees of external rotation. In addition, the study attempted to determine if there was a relationship between the range of external rotation (ER) and internal rotation (IR) and the threshold to detection of passive motion values. Shoulder kinesthesia was assessed in the dominant and nondominant shoulders of 20 collegiate athletes participating in unilateral upper extremity sports. A proprioceptive testing device passively moved the shoulder into internal and external rotation. The dominant shoulder had a significantly greater difficulty detecting motion compared with the nondominant arm at both 0 degrees and 75 degrees of external rotation. Both shoulders exhibited enhanced kinesthesia (lower threshold to detection of passive motion scores) at 75 degrees of external rotation compared with 0 degrees, where the glenohumeral joint capsule is relatively taut. The results of this study suggest that healthy upper extremity athletes may have kinesthetic deficits in their throwing shoulder compared with their nondominant shoulder. PMID- 7773275 TI - A comparison of torque production during dynamic strength testing of shoulder abduction in the coronal plane and the plane of the scapula. AB - Quantitative measurement of the shoulder abductors is important in a comprehensive assessment of shoulder muscle performance. Testing in traditionally accepted positions may be compromising to the glenohumeral static and dynamic stabilizers; therefore, there is a need to investigate testing in other planes of motion. The purpose of this study was to compare torque produced during isokinetic testing of shoulder abduction in the coronal plane and the scapular plane. Twenty female subjects with no previous shoulder pathology were tested at 90 degrees/sec and 210 degrees/sec in the coronal and scapular planes using the Cybex II isokinetic dynamometer. Both peak torque and mean peak torque of three trials were recorded. A t test for related samples (p < .05) revealed no significant difference in the peak and mean peak torque produced at each speed. Using a two-way analysis of variance with repeated measures, no significant difference was found in the peak torque produced between the two planes. However, torque production at 90 degrees/sec in both test positions was significantly higher than torque production at 210 degrees/sec (F1,19 = 159.610, p < .001). Although anatomical, functional, and clinical reasons have been proposed for performing exercise and testing procedures of the shoulder abductors in the scapular plane, the results of this study indicate that in healthy young women, there is no difference in torque production between the two planes. PMID- 7773277 TI - Diabetes' sweet little mystery. PMID- 7773276 TI - Effect of running on anterior knee laxity in collegiate-level female athletes after anterior cruciate ligament reconstruction. AB - Agility running activities are commonly used in the latter stages of rehabilitation for anterior cruciate ligament (ACL) reconstruction. However, the effects of agility running on anterior knee laxity in these patients have not been examined. The purpose of this study was to examine changes in anterior knee laxity before and after 30 minutes of agility running exercise. Subjects (N = 9) were female athletes (mean age = 20.1 +/- 1.5 years; height = 171.7 +/- 10.4 cm; weight = 65.7 +/- 8.6 kg) with unilateral ACL reconstruction (central 1/3 patella tendon graft, postoperation range = 9-52 months, mean = 24.2 months). Measurements were made at 20 degrees and 90 degrees of knee flexion bilaterally with KT-1000 arthrometry (MEDmetric, San Diego, CA) and recorded in millimeters of displacement. Data were analyzed with an analysis of variance (ANOVA) with repeated measures (p < 0.05). Results showed no statistical differences between the ACL-reconstructed knee and the normal knee at 20 degrees and 90 degrees knee flexion. The authors conclude that the central 1/3 patella tendon graft performs comparable to the normal knee when stressed with agility running exercise; therefore, agility exercise is an appropriate, safe, short-term activity. PMID- 7773278 TI - The dominating effect of mutant p53. PMID- 7773279 TI - Probability and complex disease genes. PMID- 7773280 TI - "Take a break--have a quick map". PMID- 7773281 TI - Peaceful bombardment in the land of unrest. PMID- 7773282 TI - The question of heterogeneity in Marfan syndrome. PMID- 7773283 TI - Immune surveillance in colorectal carcinoma. PMID- 7773284 TI - Effect on splicing of a silent FGFR2 mutation in Crouzon syndrome. PMID- 7773285 TI - Genomic imprinting of Mash2, a mouse gene required for trophoblast development. AB - The mouse gene Mash2 encodes a transcription factor required for development of trophoblast progenitors. Mash2-homozygous mutant embryos die at 10 days postcoitum from placental failure. Here we show that Mash2 is genomically imprinted. First, Mash2+/- embryos inheriting a wild-type allele from their father die at the same stage as -/- embryos, with a similar placental phenotype. Second, the Mash2 paternal allele is initially expressed by groups of trophoblast cells at 6.5 and 7.5 days post-coitum, but appears almost completely repressed by 8.5 days post-coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2 and H19. PMID- 7773286 TI - Gene transfer and expression in progeny after intravenous DNA injection into pregnant mice. AB - Several methods that enable foreign genes to be transferred directly into germ cells and adult animals have been developed, which have stimulated great interest in manipulating genes in vivo. However, there have been no methods available for introducing genes into fetuses. We report here that a single intravenous injection of expression plasmid: lipopolyamine complexes into pregnant mice resulted in successful gene transfer into the embryos. The transgenes thus introduced were expressed in the fetuses and newborn progeny. This simple and new method of gene transfer into embryos will facilitate rapid analysis of transgene effects in the fetuses and will be useful for studying gene-deficient animal models to gain transgene functions at desired stages of embryogenesis. PMID- 7773287 TI - Mutation of the MXI1 gene in prostate cancer. AB - The Mxi1 protein negatively regulates Myc oncoprotein activity and thus potentially serves a tumour suppressor function. MXI1 maps to chromosome 10q24 q25, a region that is deleted in some cases of prostate cancer. We have detected mutations in the retained MXI1 alleles in four primary prostate tumours with 10q24-q25 deletions. Two tumours contained inactivating mutations, whereas two others contained the identical missense mutation. Fluorescence in situ hybridization also demonstrated loss of one MXI1 allele in an additional tumour lacking chromosome 10 abnormalities. MXI1 thus displays allelic loss and mutation in some cases of prostate cancer that may contribute to the pathogenesis or neoplastic evolution of this common malignancy. PMID- 7773288 TI - Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. AB - Transplantations for neurological disorders are limited by the supply of human fetal tissue. To generate larger numbers of cells of appropriate phenotype, we investigated whether human neural progenitors expanded in vitro could be modified with recombinant adenoviruses. Strong expression of beta-galactosidase was obtained in vitro. Two or three weeks after transplantation of engineered cells to the rat brain, we observed a small percentage of surviving neuroblasts strongly expressing beta-galactosidase in four out of 13 rats. Thus human precursor cells that have been genetically modified using adenoviruses are a promising tool for ex vivo gene therapy of neurodegenerative diseases. PMID- 7773289 TI - A 2D crossover-based map of the human X chromosome as a model for map integration. AB - We have constructed a two-dimensional map of 243 markers on the X chromosome. The average distance between markers ordered by two recombinants is 5.4 centiMorgans (cM), which is reduced to 3.2 cM using a less stringent criterion of one recombinant. Map resolution is enhanced by replacing the usual reference marker format with a 2D format, and the two-recombinant rule is more conservative than the lod 3.0 criterion for order. Taken together, crossover mapping and the 2D format produces maps with greater reliability and higher resolution than maps constructed using currently accepted standards. This first high-density crossover based map of an entire human chromosome provides a model for integrating physical and genetic maps. PMID- 7773290 TI - Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. AB - We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin. PMID- 7773292 TI - The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription. AB - Genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) is inherited as a polygenic trait. One of the loci implicated in IDDM is a polymorphic minisatellite 5' of the human insulin (INS) gene on chromosome 11. This insulin linked polymorphic region (ILPR) is composed of tandemly repeated sequences, which fall into three size classes: IDDM is strongly associated with short ILPR alleles. We now show that the ILPR is capable of transducing a transcriptional signal in pancreatic beta-cells, with a long ILPR possessing greater activity than a short ILPR. The ILPR contains numerous high-affinity binding sites for the transcription factor Pur-1, and transcriptional activation by Pur-1 is modulated by naturally occurring sequences in the ILPR. Our results demonstrate a possible function for this unique minisatellite, which may have implications for type 1 diabetes. PMID- 7773291 TI - Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. AB - The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5. By 'cross match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself. Other polymorphisms were systematically excluded as primary disease determinants. Transmission of IDDM2 may be influenced by parent-of-origin phenomena. Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR. Allelic variation at VNTRs may play an important general role in human disease. PMID- 7773293 TI - A missense mutation in the glucagon receptor gene is associated with non-insulin dependent diabetes mellitus. AB - Non-insulin-dependent diabetes mellitus (NIDDM) affects about 5% of the world population. The disease presents a polygenic mode of inheritance, but mechanisms and genes involved in late-onset NIDDM are largely unknown. We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late-onset NIDDM. This mutation was highly associated with NIDDM in a pooled set of French and Sardinian patients (chi 2 = 14.4, P = 0.0001) and showed some evidence for linkage to diabetes in 18 sibships from 9 French pedigrees (chi 2 = 6.63, P < 0.01). Receptor binding studies using cultured cells expressing the Gly40Ser mutation demonstrate that this mutation results in a receptor which binds glucagon with a three-fold lower affinity compared to the wild type receptor. PMID- 7773294 TI - A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. AB - To test the behaviour of a mutant form of p53 in the presence and absence of wild type p53 in vivo, we mated p53-deficient mice containing a p53 null allele to transgenic mice containing multiple copies of a mutant p53 gene (Val 135). Animals hemizygous for the endogenous wild-type p53 gene with the mutant transgene exhibited accelerated tumour development and an altered tumour spectrum compared to their non-transgenic counterparts. In contrast, transgenic and non transgenic animals nullizygous for endogenous p53 developed tumours at the same rate. Thus, the mutant Val-135 p53 allele may act in vivo in a dominant negative manner in the presence of wild-type p53 but does not display gain of function activity in the absence of wild-type p53. PMID- 7773295 TI - Gamete-specific methylation correlates with imprinting of the murine Xist gene. AB - We have investigated the potential role of DNA methylation as a regulator of imprinted Xist expression in mouse preimplantation embryos. The active paternal allele was found to be unmodified in sperm at CpG loci near the 5' end of the gene transcription unit. In contrast, on the inactive maternal allele, these same sites are initially methylated in the oocyte and then remain modified in the early embryo. In the male germ line, these methyl moieties are removed during spermatogenesis, and this occurs before the programmed reactivation of Xist in the testis. This represents a clear-cut example of a potential methylation imprinting signal that is reprogrammable and gamete derived. PMID- 7773296 TI - Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X-inactivation. AB - Preferential paternal X-inactivation in the extra-embryonic tissues of the female mouse embryo is correlated with imprinted expression of the paternal allele of the Xist gene in pre-implantation development. Here we examine 11 CpG sites in Xist to determine whether differential methylation might be the molecular basis for imprinting. We find that three sites in the promoter region are methylated in eggs but not in sperm and that this differential methylation is maintained to the blastocyst stage when the paternal X-inactivation occurs. This is the first example of a primary gametic methylation imprint governing differential expression of parental alleles in pre-implantation embryos. PMID- 7773297 TI - Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. AB - Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. Affected individuals display features similar to those seen in homozygous achondroplasia. Mutations causing achondroplasia are in FGFR3, suggesting that mutations in this gene may cause TD. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 16 of 16 individuals with one type of TD. Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein. None of these mutations were found in 50 controls showing that mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder. PMID- 7773299 TI - Limitations of probit plots in pharmacogenetics: requirement of genetic analyses to test hypotheses based on graphical methods. PMID- 7773298 TI - Nomenclature for N-acetyltransferases. AB - A consolidated classification system is described for prokaryotic and eukaryotic N-acetyltransferases in accordance with the international rules for gene nomenclature. The root symbol (NAT) specifically identifies the genes that code for the N-acetyltransferases, and NAT* loci encoding proteins with similar function are distinguished by Arabic numerals. Allele characters, denoted by Arabic numbers or by a combination of Arabic numbers and uppercase Latin letters, are separated from gene loci by an asterisk, and the entire gene-allele symbols are italicized. Alleles at the different NAT* loci have been numbered chronologically irrespective of the species of origin. For designation of genotypes at a single NAT* locus, a slash serves to separate the alleles; in phenotype designations, which are not italicized, alleles are separated by a comma. PMID- 7773300 TI - Modulation of xenobiotic-inducible cytochrome P450 gene expression by dexamethasone in primary rat hepatocytes. AB - Our previous studies (Sidhu JS et al. Arch Biochem Biophys 1993: 301, 103-113; Sidhu JS et al. In Vitro Toxicol 1994: 7, 225-242) demonstrated the importance of culturing primary rat hepatocytes with an overlay of extracellular matrix (ECM), together with optimal media formulations (Williams' E or Chee's), to efficiently maintain in vivo-like responsiveness of phenobarbital (PB)-inducible cytochrome P450 genes in vitro. In the present report, we have characterized culture conditions further by examining individual and interactive effects of dexamethasone (Dex) and PB on CYP2B1, CYP2B2, and CYP3A1 expression. Dex alone was not effective in enhancing CYP2B1 or CYP2B2 expression levels. However, together with PB, addition of low concentrations (10(-9)-10(-8) M) of Dex resulted in a marked potentiation of PB-inducible P450 gene expression. In contrast, at levels > 10(-7) M, Dex profoundly inhibited PB induction of the CYP2B1 and CYP2B2 genes. The overall stimulatory response to Dex was more dramatic in cells cultured in Williams' E than in Chee's medium. Similarly, concentrations of PB > 0.5 mM resulted in substantially reduced levels of CYP2B1 and CYP2B2 induction than those attainable at lower PB concentrations. These results suggest that Dex and PB function cooperatively to regulate the CYP2B1 and CYP2B2 genes, and that composite interactions may either negatively or positively regulate expression, in a concentration-dependent manner. CYP3A1 was not regulated in a similar biphasic fashion, as this gene was fully responsive even at high dose levels of PB or Dex. With respect to other marker genes evaluated, high Dex concentrations (> 10(-7) M) were only marginally inhibitory to beta naphthoflavone-mediated induction of CYP1A1 and CYP1A2 mRNAs, and did not perturb expression of the liver-selective serum albumin gene. Addition of Dex was critical, however, to maintain glutathione S-transferase Pi expression, a marker of hepatocyte dedifferentiation, in the repressed state. Defining optimal culture conditions for maintaining hepatocyte differentiation in vitro are requisite for establishing primary culture models enabling investigation of the molecular mechanisms of PB-mediated gene regulation. PMID- 7773301 TI - Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. AB - Cytochrome P450 (CYP) 2C9 catalyses the metabolism of a wide range of drugs. Previous studies have shown the differences in the amino acid composition among CYP2C9 variants at Cys144/Arg, Tyr358/Cys, Leu359/Ile, and Gly417/Asp. PCR endonuclease digestion methods have been developed to detect these four possible polymorphisms. The T416-->C mutation in exon 3 of CYP2C9 (Cys144-->Arg) creates an Ava II site. In the 135 subjects we tested, all leukocyte DNA samples showed a complete Ava II digestion indicating homozygous C416 (Arg144). A Tyr358-->Cys mutation will create a Nsi I site at codon 1057-1063 in exon 7. In 40 subjects tested, all samples showed negative results. DNA sequencing on a few samples showed Tyr358Ile359. A mismatched PCR primer pair was then designed to detect codon C1061-->A (Leu359-->Ile) mutation. In 115 subjects tested, 111 samples showed a complete Nsi I digestion (Ile359) and four samples showed heterozygous results. Another mismatched PCR primer pair was used to confirm the C1061 codon in heterozygous subjects. The four heterozygous subjects showed partial digestion with endonuclease Kpn I, which confirmed the heterozygous Ile/Leu at amino acid 359. The G1236-->A mutation in exon 8 of CYP2C9 (Gly417-->Asp) creates a Hph I site. In all 46 subjects, homozygous G1236 (Gly417) was found. Most Chinese subjects actually have Arg144 Tyr358 Ile359 Gly417 in CYP2C9 as previously reported human-2. Furthermore, we found an A-->T (+12 position in intron 2) mutation in our CYP2C9 sequencing process. The mutation creates a NIa III site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773302 TI - (S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7. AB - 1,4-Benzodiazepine anxiolytics such as diazepam and halazepam are converted in vivo to oxazepam, an active metabolite with a hydroxyl group at the asymmetric C3 position. D-glucuronic acid couples with the C3 hydroxyl group of oxazepam to form pharmacologically inactive diastereomeric glucuronide conjugates. Conjugation with glucuronic acid is catalysed by the microsomal UDP glucuronosyltransferase (UGT) enzyme system, which includes an undetermined number of isozymes. Although 1,4-benzodiazepines are ultimately cleared as oxazepam glucuronide, little is known about the particular UGT isozyme(s) responsible for the conjugation at the C3 position of these molecules. Microsomal preparations from three human livers were used to study the glucuronidation of (R,S)oxazepam in vitro. The predominant formation of the S- over the R glucuronide was reflected by the kinetic parameters: For (S)oxazepam glucuronide, the constants were Km = 0.18 +/- 0.02 mM and Vmax = 202.6 +/- 25.0 nmol min-1 per mg protein; for (R)oxazepam glucuronide, they were Km = 0.22 +/- 0.02 mM, Vmax = 55.4 +/- 9.5 nmol min-1 per mg protein. Inhibition studies suggest that the two diastereomeric glucuronidations are catalysed by different UGT isozymes. That is, there was competitive inhibition of (S)oxazepam glucuronidation by non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen while (R)oxazepam glucuronidation was not equally inhibited by these compounds. The order of potency of inhibitors of (S)oxazepam glucuronidation in this study was the same as the rank order of substrates conjugated by UGT2B7; hyodeoxycholic acid, estriol, (S)naproxen, ketoprofen, ibuprofen, fenoprofen, clofibric acid, and morphine (in descending order). The inhibition profile of (S)oxazepam glucuronidation suggests that UGT2B7 is the catalysing enzyme. PMID- 7773304 TI - Studies on interindividual variations of CYP2E1 using chlorzoxazone as an in vivo probe. PMID- 7773303 TI - Lack of a genetic polymorphism in the glucuronidation of fenofibric acid. PMID- 7773305 TI - Flavanone 3-hydroxylase transcripts and flavonol accumulation are temporally coordinate in maize anthers. AB - Flavanone 3-hydroxylase (F3H) activity is necessary for the production of both flavonols and anthocyanins. Flavonols are required for functional pollen in maize whereas anthocyanins are non-essential pigments. A cDNA for F3H was isolated from Zea mays using a heterologous sequence from Antirrhinum majus. Comparison of the deduced amino acid sequence of maize F3H with other F3H sequences confirmed that the protein is highly conserved among widely divergent plant species. The F3H gene is present in a single copy located at the tip of chromosome 2S. High levels of F3H gene expression were detected in pigmented husk and 26-day postpollination kernels; lower levels in 18-day postpollination kernels and in coleoptiles of germinating seedlings. Slot blot analysis showed that F3H transcript levels in young seedlings are increased by high fluence-rate white light treatment in the presence of the anthocyanin regulatory gene -r. HPLC analysis of extracts from developmentally staged anthers showed that flavonol accumulation begins at the uninucleate microspore stage, continues until maturity, and is not controlled by r. When the expression pattern of several flavonoid biosynthetic genes was analyzed during microsporogenesis, only F3H transcript accumulation was coordinate with the appearance of flavonols in anthers. PMID- 7773306 TI - Correlation between the induction of a gene for delta 1-pyrroline-5-carboxylate synthetase and the accumulation of proline in Arabidopsis thaliana under osmotic stress. AB - The isolation and characterization is reported of a cDNA for delta 1-pyrroline-5 carboxylate (P5C) synthetase (cAtP5CS), an enzyme involved in the biosynthesis of proline, from a cDNA library prepared from a dehydrated rosette plant of Arabidopsis thaliana. Southern blot analysis suggested that only one copy of the corresponding gene (AtP5CS) is present in A. thaliana. The deduced amino acid sequence of the P5CS protein (AtP5CS) from A. thaliana exhibited 74% homology to that of the P5CS from Vigna aconitifolia. Northern blot analysis revealed that the gene for P5CS was induced by dehydration, high salt and treatment with ABA, while it was not induced by heat or cold treatment. Moreover, the simultaneous accumulation of proline was observed as a result of the former treatments in A. thaliana. A cDNA for P5C reductase (cAtP5CR) was also isolated from A. thaliana and Northern blot analysis was performed. The AtP5CR gene was not induced to a significant extent by dehydration or high-salt stress. These observations suggest that the AtP5CS gene plays a principal role in the biosynthesis of proline in A. thaliana under osmotic stress. PMID- 7773307 TI - Functional expression of Saccharomyces cerevisiae CYP51A1 encoding lanosterol-14 demethylase in tobacco results in bypass of endogenous sterol biosynthetic pathway and resistance to an obtusifoliol-14-demethylase herbicide inhibitor. AB - Nicotiana tabacum protoplasts have been transformed by Agrobacterium tumefaciens containing a T-DNA in which the gene CYP51A1 encoding lanosterol-14-demethylase (LAN14DM) from Saccharomyces cerevisiae is under the control of a cauliflower mosaic virus (CaMV) 35S promoter. Two transformants strongly expressed the LAN14DM as shown by Northern and Western experiments. These transgenic calli were killed by LAB 170250F (LAB) (a phytotoxic fungicide inhibiting both plant obtusifoliol-14-demethylase (OBT14DM) and LAN14DM) but were resistant to gamma ketotriazole (gamma-kt), a herbicide which has been shown to inhibit OBT14DM but not LAN14DM at a concentration that was lethal to control calli. However, these transgenic calli were killed by mixtures of gamma-kt plus fungicide inhibitors of LAN14DM such as ketoconazole, itraconazole or flusilazole which alone were not effective. Further analysis of the transgenic calli grown in the presence of gamma-kt showed that their delta 5-sterol content was close to that of untreated control calli obtained from protoplasts transformed with control plasmid; this is in agreement with evidence that the LAN14DM expressed from the transgene could bypass the blocked OBT14DM by using the plant substate obtusifoliol. In contrast, control calli when treated with gamma-kt, displayed a sterol content strongly enriched in 14 alpha-methyl sterols and depressed in physiological delta 5 sterols. When the transgenic calli were cultured in mixtures of gamma-kt and LAN14DM inhibitors sterol compositions enriched in 14 alpha-methyl sterols were obtained, reflecting a strong inhibition of both 'endogenous' OBT14DM and 'exogenous' LAN14DM. Taken together these results show that in tobacco calli transformed with CYP51A1, resistance to a triazole herbicide arises from expression of a functional LAN14DM enzyme; its activity in transgenic tissues creates a bypass of the sterol biosynthetic pathway at the 14-demethylase level when this latter is blocked by an OBT14DM herbicide inhibitor. PMID- 7773308 TI - Co-expression of native and introduced genes reveals cryptic regulation of HMG CoA reductase expression in Arabidopsis. AB - In eukaryotes, all isoprenoid compounds share a common precursor, mevalonic acid, whose synthesis is catalyzed by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. As one step towards a better understanding of the role that this enzyme plays in coordinating isoprenoid biosynthesis in plants, Arabidopsis thaliana HMG CoA reductase was ectopically expressed in transgenic Arabidopsis plants. By using this molecular genetic approach, several novel and fundamental observations have been made regarding isoprenoid biosynthesis in Arabidopsis. First, it was demonstrated that the overexpression of authentic Arabidopsis HMG CoA reductase is not sufficient to alter the bulk synthesis and accumulation of the abundant end products of the plant isoprenoid pathway. Second, active transcription of the transgene appears to co-activate and deregulate expression of the native gene, resulting in a striking elevation of HMG CoA reductase mRNA levels. Finally, although very high levels of HMG CoA reductase mRNA were expressed in these transgenic plants, only modest increases in enzyme activity could be detected. Taken together, these data suggest that HMG CoA reductase expression is regulated at multiple levels in plants as well as animals, and they provide a foundation for elucidating the molecular mechanisms for mevalonate regulation in A. thaliana. PMID- 7773309 TI - An aldose reductase homologous gene from barley: regulation and function. AB - The expression of a barley gene homologous to aldose reductase and aldehyde reductase is restricted to the embryo and temporally correlated with its acquisition of desiccation tolerance. In the work presented, two aspects of this barley gene were investigated: its transcriptional regulation and the initial characterization of the enzymatic function. The transcriptional regulation of the gene was studied in transgenic tobacco by analysing the expression of chimeric genes containing 5' sequences of the barley gene transcriptionally fused to the GUS reporter gene. This functional analysis of the promoter revealed that a 1364 bp 5' fragment confers the appropriate pattern of expression to the reporter gene in tobacco and that a short promoter fragment (-114 to +75) containing the sequence TACGTGGC, homologous to plant G-box elements, is sufficient for developmental expression during embryogenesis. To investigate the enzymatic properties of the gene product the wild-type protein and a mutant carrying a lysine 259 to methionine substitution were overexpressed in a procaryotic system and purified to homogeneity. The wild-type protein exhibits aldose reductase activity in the reduction of DL-glyceraldehyde and D-erythrose specifically using NADPH as co-factor whereas the mutant shows markedly reduced activity. However, the barley protein possesses some properties different to those of animal aldose and aldehyde reductases and its biological target still needs to be identified. PMID- 7773311 TI - Expression of a chimeric uidA gene indicates that polycistronic mRNAs are efficiently translated in tobacco plastids. AB - Polycistronic mRNAs are the predominant form of plastid primary transcripts. To determine if there is internal initiation of translation of promoter-distal open reading frames, a promoterless uidA reporter gene was integrated into the tobacco plastid genome downstream of the rbcL gene. Monocistronic uidA mRNA does not accumulate from the promoterless uidA construct. However, due to inefficient rbcL transcription termination, a polycistronic transcription unit is created that contains the uidA gene as the second cistron. Numerous stop codons in all three reading frames between the rbcL and uidA coding regions ensure that translation of uidA initiates only from the correct start codon. The encoded reporter gene product, beta-glucuronidase (GUS) accumulates to high levels in the transplastomic plants indicating that promoter-distal cistrons can be efficiently translated in plastids. PMID- 7773310 TI - A novel Arabidopsis type 1 protein phosphatase is highly expressed in male and female tissues and functionally complements a conditional cell cycle mutant of Aspergillus. AB - Type 1 protein phosphatases are very highly conserved throughout eukaryotes where they regulate a number of key metabolic and morphogenetic processes. A cDNA, AtPP1bg, representing a new member of the type 1 protein phosphatase gene family in Arabidopsis has been isolated on the basis of hybridization with the Aspergillus bimG protein phosphatase gene. The AtPP1bg gene potentially encodes a 37 kDa protein very closely related to PP1 but with divergent N- and C-termini. The predicted amino acid sequence shows 71% identity to the ORF of the bimG gene. When expressed in Aspergillus under the alcA promoter, this phosphatase complements the temperature-sensitive bimG11 mutation allowing nearly normal vegetative growth at 37 degrees C (but not at 42 degrees C). Notably, the plant PP1 does not support morphogenesis (conidiation) at 37 degrees C. This may indicate that conidophore formation has particular phosphatase requirement(s) which the plant PP1 cannot supply. The pattern of expression of the AtPP1bg transcript has been studied during development of the plant. In situ hybridization of Arabidopsis with antisense probes shows that this phosphatase gene is expressed at a low level throughout the plant, but is strongly upregulated within developing flowers, especially in the tapetum, the developing and mature pollen and in the ovaries. This implies that the AtPP1bg either has a specialized role in the formation of these organs, or that there is an increased requirement for protein phosphatase 1 at these stages. It was found that the level of AtPP1bg transcript, as judged by the relative intensity of staining in different cells within the floral meristems, did not vary during the cell cycle. PMID- 7773312 TI - A novel Ti-plasmid-convertible lambda phage vector system suitable for gene isolation by genetic complementation of Arabidopsis thaliana mutants. AB - A new lambda phage vector system, lambda TI, has been constructed to facilitate genetic complementation of higher plant mutations. The lambda TI vectors are stable, and by using the Cre-lox site-specific recombination, are automatically convertible into Ti-plasmid binary vectors which are capable of expressing genes in higher plants. Two lambda TI vectors were constructed: (i) lambda TI1, which can generate a Ti-plasmid that contains the cauliflower mosaic virus (CaMV) 35S promoter and is suitable for the expression of cDNA in transformed plants and (ii) lambda TI2, which can generate a Ti-plasmid with the multicloning site (MCS). cDNA and genomic libraries, which were constructed from the cruciferous plant Arabidopsis thaliana in these lambda TI vectors, can be probed by large DNA fragments of more than 100 kb, such as yeast artificial chromosomes (YACs), enabling the direct screening of the clones in the chromosome region containing a specified genetic locus. These libraries will certainly become powerful tools for the genetic complementation of Arabidopsis mutant phenotypes by quickly providing transformation-competent clones. PMID- 7773313 TI - Three families of thiol peptides are induced by cadmium in maize. PMID- 7773314 TI - Uroflowmetry in elderly men. AB - In the evaluation of lower-urinary-tract symptoms, uroflowmetry has played a major role for decades due to its noninvasiveness and simplicity to perform. However, several pitfalls have to be taken into account as mentioned in this review. They include artifacts, circadian changes, observer variation, minimal volume, association with infravesical obstruction, relevant variables, reference values, and clinical applicability. Thus, uroflow should be interpreted with proper caution. PMID- 7773315 TI - Basics of pressure-flow studies. AB - Pressure-flow studies of voiding contain information about urethral resistance or obstruction and about the detrusor contraction or contractility. A fundamental problem, discussed in this paper, is how to disentangle these two. A second, more difficult, problem is how to evaluate them in a simple, clinically useful way. Plots of detrusor pressure against flow rate during the course of voiding offer a helpful adjunct to conventional urodynamic curves showing changes with time. Many ways of assessing urethral obstruction from these plots have been proposed that have somewhat differing aims but, in practice, produce rather similar results. Agreement on a standard method is needed to allow the comparison of results obtained in different centers. Detrusor contractility has been less extensively studied but methods for assessing it are available. PMID- 7773317 TI - Analysis of bladder-outlet function with the linearized passive urethral resistance relation, linPURR, and a disease-specific approach for grading obstruction: from complex to simple. AB - The concept of the passive urethral resistance relation (PURR) to quantify bladder outflow conditions in few parameters from the complex pressure/flow relation is generally accepted. The most simple, yet realistic, linearized format is the linear PURR (linPURR). This two-dimensional format allows clear identification of individual outflow conditions with distinction of different obstruction types. Unequivocal grading of obstruction, however, requires a one dimensional format. Theoretical considerations show that voiding function can be completely defined by a single parameter only when detrusor strength and obstruction type are uniform. This can be achieved with a disease-specific approach such as our pressure/flow diagram, which is specific for prostatic obstruction. It allows grading of obstruction stepwise for clinical decisions making or on a continuous scale for statistical applications using the maximal flow rate with related detrusor pressure as a single data point alone. Adding the actual linPURR to the diagram offers the unique feature of inherent conceptual quality control, relevant for individual assessment. The detrusor-adjusted mean PURR factor (DAMPF) is an alternative format of reducing the PURR to a single number, excluding at least the impact of variable detrusor strength, a conceptual advantage when the obstruction type is less uniform. The voiding pressure at maximal flow is a suitable parameter for most simple obstruction grading. Its validity can be significantly enhanced only when it is used in a disease-specific format, such as our pressure/flow diagram in combination with linPURR and DAMPF. Computerization does not improve the results of manual graphical analysis. Much more important is the clear conceptual definition and transparent application. More sophisticated computer-dependent methods such the original PURR/DURR and the three-parameter model can abstract more detailed information about outflow conditions, which requires expertise in their application and perfect data quality, but this does not result in better obstruction grading. PMID- 7773316 TI - Analysis of pressure-flow data in terms of computer-derived urethral resistance parameters. AB - The simultaneous measurement of detrusor pressure and flow rate during voiding is at present the only way to measure or grade infravesical obstruction objectively. Numerous methods have been introduced to analyze the resulting data. These methods differ in aim (measurement of urethral resistance and/or diagnosis of obstruction), method (manual versus computerized data processing), theory or model used, and resolution (continuously variable parameters or a limited number of classes, the so-called monogram). In this paper, some aspects of these fundamental differences are discussed and illustrated. Subsequently, the properties and clinical performance of two computer-based methods for deriving continuous urethral resistance parameters are treated. PMID- 7773318 TI - A clinical view of pressure-flow studies. AB - Lower-urinary-tract symptoms might be due to bladder dysfunction, infravesical obstruction, or both, and these conditions give rise to the same type of symptoms. Classification of symptomatic benign prostatic hyperplasia (BPH) patients into obstructed or unobstructed cases can be done only by pressure-flow studies. This classification has been demonstrated to be of predictive value for the outcome of surgical treatment, both symptomatically and urodynamically. Pressure-flow studies are therefore helpful in the pretreatment workup of patients in regard to both diagnosing the underlying pathophysiology and, consequently, stratifying patients for different treatments or watchful waiting. Different methods of interpreting pressure-flow investigations share the same theoretical foundation and therefore have only minor differences in classifying patients into obstructed or unobstructed cases. The more advanced methods make a more differentiated classification possible, but these are currently mostly of theoretical value in research. PMID- 7773319 TI - Is there a correlation between prostate size and bladder-outlet obstruction? AB - This retrospective study was conducted in 521 men with micturition complaints to determine the relationship between prostate size and bladder-outlet obstruction. Analysis showed a statistically significant correlation between bladder-outlet obstruction and prostate size. Urodynamic bladder-outlet obstruction was confirmed in 90% of the patients with a prostate size of more than 80 cm3. In 32% of the patients with a prostate smaller than 40 cm3, no urodynamic evidence of bladder-outlet obstruction was found. There was no correlation between symptom scores (Madsen and I-PSS) and the grade of bladder-outlet obstruction or prostate size. We conclude that precise determination of the prostate size and urodynamics investigations are important (complementary) parameters in the assessment of elderly men with micturition complaints. PMID- 7773320 TI - Joint Commission update: equipment management in the environment of care. PMID- 7773321 TI - Comparison of D10-value accuracy by the limited Spearman-Karber procedure (LSKP), the Stumbo-Murphy-Cochran procedure (SMCP), and the survival-curve method (EN). AB - The decimal reduction time (D10) may be determined by any of several methods, including the limited Spearman-Karber procedure (LSKP), the Stumbo-Murphy-Cochran procedure (SMCP), and the survival-curve method (EN). The International Organization for Standardization (ISO) endorses the LSKP and the EN. Most Japanese and German industries utilize the SMCP and the EN for calculation of the D value. A presentation at an ISO meeting suggested that the SMCP was less accurate than the LSKP, and the ISO recommended abandoning the SMCP. The paper concerning the accuracy comparison among these methods has not been published. Therefore, in order to examine whether the SMCP was truly inferior to the LSKP, the Japanese delegates to the ISO compared the accuracies of D10 values obtained with these methods by simulation and in experimental procedures using a biological indicator (BI) and a biological indicator evaluator resistometer (BIER) with ethylene oxide gas sterilization. The results indicate that the SMCP was not consistently less accurate than the LSKP in determining D10. PMID- 7773322 TI - Glucose biosensors with enzyme entrapped in polymer coating. AB - The pursuit of reliable biosensors for measuring glucose levels has been ongoing for decades. Their importance lies partly in the development of the implantable artificial pancrease, which can be used to deliver insulin to diabetics without the need to test glucose levels externally, with automatic delivery based on physiologic demand. Glucose sensors can also be used in short-term monitoring of glucose levels in hospitals and clinical laboratories. Three types of glucose biosensors were studied. All were based on a two-electrode system: an insulated platinum wire as a hydrogen peroxide electrode, and a silver wire twisted around the platinum wire as both a reference and a counter electrode. Each was coated with the enzyme glucose oxidase entrapped in a polymer matrix of cellulose acetate (CA) or poly 2-hydroxyethyl methacrylate (HEMA), then dip-coated by an additional polymer coating of polyvinylchloride (PVC), polyurethane (PU), or HEMA. The experiments were designed mainly to study the effectiveness of polymer coatings as diffusion-limiting membranes. The effect of each coating on the linear response to glucose concentration was examined. It was shown that additional (multiple) coatings can increase the linearity of the sensor response. The best results were obtained when the sensor was PVC-dip-coated three times. This preparation had a linear response up to 600 mg/DL glucose concentration. The sensors coated with PU and HEMA have linearity up to 280 and 240 mg/DL glucose concentrations, respectively. It was also shown that the coatings reduce interference from certain body chemicals. PMID- 7773323 TI - Clinical monitoring of inhaled nitric oxide: comparison of chemiluminescent and electrochemical sensors. AB - In view of the rapidly increasing use of inhaled nitric oxide for infants with potentially reversible pulmonary hypertension, the ability to accurately measure nitric oxide and its by-products is an increasingly important safety issue. The authors evaluated the abilities of two chemiluminescent analyzers and two electrochemical sensors to detect known concentrations of nitric oxide (NO) and nitrogen dioxide (NO2). A calibrated mass spectrometer was utilized to determine the reference levels of NO2. Mass flowmeters calibrated with bubble flowmeters and an audited cylinder of NO were utilized to determine the levels of NO. In a test laboratory environment, all sensors yielded reasonably accurate measurements of NO. It was observed, however, that the amounts of NO recorded by the candidate analyzers in an 82% oxygen environment were slightly low compared with reference methods. The chemiluminescent analyzers consistently underread the true amounts of NO2 in a high-oxygen environment, producing negative concentrations on one instrument. Some monitors that are being clinically utilized to measure NO were designed for industrial and environmental applications in which the ambient oxygen concentrations are less than 21%. In the presence of higher oxygen concentrations, such analyzers can significantly underread the amounts of NO2 that are present, possibly because of reaction quenching or other effects. Measurements of NO and its by-products should be performed using analyzers that have been appropriately tested and calibrated with known concentrations of NO and NO2 prior to their clinical application. PMID- 7773324 TI - AAMI standards program annual report, 1994. PMID- 7773325 TI - Red blood cell physiology. PMID- 7773326 TI - Managing assertively: specific tactics for clinical engineering managers. PMID- 7773327 TI - Clinical information systems: considerations in selecting the hospital department with primary responsibility. PMID- 7773328 TI - Mitochondrial DNA variation in an experimental stock of gilthead sea bream (Sparus aurata). AB - We present a restriction site map for the mitochondrial DNA of the gilthead sea bream and the consensus sequence for a region of the mitochondrial cytochrome b gene. Restriction site and nucleotide sequence analysis was used to obtain individual mitotype profiles in a broodstock used for genetic studies. Eight mitotypes were detected among 33 animals assayed. In combination with hypervariable nuclear markers, this variation can be used to identify the parents of any offspring in mass matings and, also, to determine which of the two parents donated the egg and who donated the sperm. On the basis of restriction site variation, the Greek stock analyzed here is very similar to an Israeli stock described in an earlier publication. It is not known if this similarity will hold when the Israeli stock is examined for sequence variation. PMID- 7773329 TI - Somatolactin, a novel pituitary protein: isolation and characterization from Sparus aurata. AB - The complete amino acid sequence of somatolactin, a new pituitary protein belonging to the growth hormone/prolactin family, from the gilthead sea bream Sparus aurata has been determined. Somatolactin was isolated from the pituitary by alkaline extraction, gel filtration on a Sephadex G-100 column, and reversed phase high-performance liquid chromatography (rpHPLC) on a TSK gel ODS-120T column. The purified protein was confirmed to be somatolactin by immunoblotting using chum salmon somatolactin antisera. It was found that Sparus aurata somatolactin consists of two forms; one form (28 kD) is probably a glycosylated form, while the other (25 kD) is a simple protein form, as was found also in Atlantic cod. The somatolactin consists of 207 amino acids that show remarkable conservation among fish somatolactins. PMID- 7773330 TI - Rapid differentiation of hyperthermophilic Archaea by restriction mapping of the intergenic spacer regions of the ribosomal RNA operons. AB - We report a sensitive and convenient method for rapid differentiation of new isolates of hyperthermophilic Archaea. Polymerase chain reaction (PCR) was used to amplify the intergenic spacer regions of the ribosomal RNA operons of eight Archaea. Spacer regions from one Euryarcheote, Pyrococcus furiosus, and one Crenarcheote, Pyrodictium brockii, were sequenced completely. Restriction fragment length polymorphism (RFLP) analyses were performed on the spacer regions from eight hyperthermophilic Archaea, and the restriction patterns were used as fingerprints for six known strains and two isolates. The PCR-RFLP method used in this study allowed the differentiation of seven of the eight strains tested and could be generally applicable to all the Archaea. PMID- 7773331 TI - Genomic basis for antifreeze peptide heterogeneity and abundance in an Antarctic eel pout: gene structures and organization. AB - Type III antifreeze protein (AFP) in the Antarctic eel pout (Lycodichthys dearborni) occurs as a heterogeneous family of three major and at least five minor variants collectively maintained at high year-round blood levels (> 20 mg/ml). Two major AFPs (RD1, RD2) are 7 kD in size, and the third (RD3) is 14 kD and is composed of two 7-kD AFP domains linked by a 9-residue connector. The genomic basis for the heterogeneity and abundance of these AFPs was investigated in this study. Genomic library screening statistics and restriction mapping analyses of 16 genomic clones together indicate an AFP gene family of over 40 genes, which would provide a sizable gene dosage for high AFP output. Two genomic clones, each containing 2 AFP genes, were characterized in detail. Three of the genes, were characterized in detail. Three of the genes encode the 7-kD AFP RD2, and are arrayed in direct 8.3-kb tandem repeats. The three gene sequences are nearly 100% identical for a distance of over 3 kb (inclusive of 1.7-kb 5' and 1 kb 3' flanking sequences), indicating strong selective pressure from the freezing Antarctic waters on maintaining functionality of AFP genes for producing adequate levels of AFPs for survival. The fourth AFP gene has multiple exons and translates into a multimeric AFP composed of at least six 7-kD AFP domains successively linked a 9-residue connector sequence similar to that of the dimeric 14-kD AFP, RD3. The presence of an unusually large (2.7-kb) AFP messenger RNA beside two small ones (0.9 kb and 0.7 kb) in Northern blot of liver RNA is consistent with the presence of a large functional multiexon AFP gene. Substantial sequence identity (83%) between the 1.2-kb introns of the multiexon AFP gene and the intron and 5' flanking sequences of RD2 genes suggests that the former could arise from recombinant events that linked two adjacent 7-kD AFP genes in the 8.3-kb tandem repeats followed by duplication events to produce the multiple exons. PMID- 7773332 TI - Maternal and embryonic provenance of a sea urchin embryo transcription factor, SpZ12-1. AB - SpZ12-1 is a zinc-finger transcription factor. Previous work has indicated that this factor functions late in embryogenesis as a spatial transcriptional repressor. We show here that this factor is present in significant quantities even in unfertilized egg cytoplasm, and in similar quantities in mesenchyme blastula-stage embryo cytoplasm. Taken together with earlier measurements of Calzone and associates, our observations indicate that SpZ12-1 enters the embryonic nuclei between late cleavage and mesenchyme blastula stages. A low prevalence mRNA encoding SpZ12-1 is also present throughout development. Translation of this mRNA could, however, easily account for the complete complement of SpZ12-1 protein in the embryo, as estimated from its DNA binding activity. SpZ12-1 probably functions at several developmental stages and is evidently of both maternal and embryonic provenance. PMID- 7773333 TI - Development of a rainbow trout pituitary cell line that expresses growth hormone, prolactin, and somatolactin. AB - A cell line, RTP-2, has been developed from a normal-appearing pituitary of an adult rainbow trout. The cells grow in L-15 basal medium, supplemented with 2.5% to 10% fetal bovine serum, and have been passaged approximately 50 times over a 2 year period. At low density the cells have a stellate shape, whereas at confluency islands of polygonal cells appear among a tangle of bipolar cells. At the ultrastructural level, most cells contain numerous lysosomes, autophagic vacuoles, and intermediate filaments, but no obvious secretory granules. Reverse transcription-polymerase chain reaction (RT-PCR) with oligonucleotides specific for growth hormone (GH), prolactin (PRL), and somatolactin (SL) as amplification primers and Southern blot hybridization of the PCR products with probes specific for GH, PRL, and SL demonstrate that this cell line expresses GH, PRL, and SL. Digestion of the GH product of RT-PCR with restriction endonuclease SalI or KpnI confirms that both rainbow trout growth hormone genes are expressed in this cell line. PMID- 7773334 TI - Two ferritin subunits of Atlantic salmon (Salmo salar): cloning of the liver cDNAs and antibody preparation. AB - The ferritin heavy (H) and middle (M) subunit cDNAs were isolated from the Atlantic salmon (Salmo salar) liver. Full-length clones encoding the ferritin M subunit of 176 residues were obtained by screening of a liver cDNA library. The evolutionary conserved iron-responsive element (IRE) was identified in the upstream untranslated region. Ferritin H cDNA was cloned by running reverse transcription-polymerase chain reaction (RT-PCR) on salmon liver mRNA. The salmon ferritin H subunit of 177 residues showed 67% sequence identity with the M subunit. Northern blot analysis revealed ferritin H mRNA in the liver, gonads, head kidney, heart, and spleen, whereas M subunit mRNA was found almost exclusively in the gonads. Polyclonal antibodies against both salmon ferritin H and M were raised in rabbits. PMID- 7773335 TI - Sequence analysis of a cDNA encoding an isotocin precursor and localization of the corresponding mRNA in the brain of the cartilaginous fish Torpedo marmorata. AB - The nucleotide sequence of a cDNA encoding an isotocin hormone precursor has been elucidated by analyzing a lambda ZAPII library constructed using poly(A)+ RNA from the brain of the cartilaginous fish Torpedo marmorata. The sequence predicts a precursor of 126 amino acid residues that consists of a signal peptide, the isotocin moiety, and a neurophysin carrier protein. In contrast to other known fish isotocin precursor sequences, the Torpedo neurophysin moiety is not extended at its carboxy-terminus by a copeptin-like sequence. The T. marmorata isotocin precursor exhibits highest amino acid sequence identity (61%) to the toad mesotocin precursor. As demonstrated by in situ hybridization, the isotocin mRNA is present in neurons of the preoptic area of the Torpedo brain. PMID- 7773337 TI - The changing and challenging ICU. PMID- 7773336 TI - A divergent cDNA homologue of the c-myc proto-oncogene in the eastern oyster Crassostrea virginica: implications for Myc evolution. AB - The polymerase chain reaction was used to identify myc-like cDNA fragments from several marine invertebrate phyla. A PCR clone produced from the eastern oyster Crassostrea virginica was subsequently used to screen a larval cDNA library, and a 1.9-kb cDNA clone was isolated and sequenced. The putative amino acid sequence encoded by this clone evidences a leucine zipper at its predicted carboxyl terminus and has an overall structural similarity to vertebrate c-myc proto oncogenes with several regions of high amino acid similarity. However, this oyster cDNA clone lacks the necessary amino acid conservation in the critical functional domains of Myc and thus is unlikely to function intracellularly in the oyster as a true homologue of vertebrate c-myc. We propose that the oyster cDNA clone described here represents a gene that has been derived from the same ancestral gene that eventually gave rise to vertebrate c-myc. Despite the apparent critical importance of the c-myc proto-oncogene in regulating cellular activities, these data suggest that the c-myc gene: (1) is unique to deuterostome phyla, and (2) assumed its critical role in regulating cell cycle activities at the divergence of the deuterostome ancestors from other protostomes during the Cambrian explosion. In support of these conclusions we present a functional model for the evolution of the Myc gene. PMID- 7773339 TI - Getting smarter--with a little help from the store. PMID- 7773338 TI - The impact of reengineering on inpatient nursing. PMID- 7773340 TI - Meeting the challenge of elder mistreatment. PMID- 7773341 TI - Establishment of primary epithelial cell culture from elutriated rat gastric mucosal cells. AB - Proliferating cells in the gastric mucosal epithelium were successfully enriched by counterflow elutriation in a medium-sized cell fraction. When inoculated on culture plates coated with E-C-L cell attachment matrix, these cells differentiated into mucus-producing cells after reaching confluence. Northern blot analysis did not detect any transcript of the proton pump, histidine decarboxylase, somatostatin, or pepsinogen I, indicating the absence of parietal, ECL, D, and chief cells in the confluent monolayer. These mucus-producing cell monolayers that respond to various growth factors may be a suitable model with which to investigate the function of gastric mucus cells in vitro. PMID- 7773342 TI - Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach. AB - The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4 degrees C for 1-3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach. PMID- 7773343 TI - Topographic study of Helicobacter pylori and HLA-DR antigen expression on gastric epithelium. AB - Helicobacter pylori and HLA-DR antigen expression on gastric epithelium, identified by an indirect immunoperoxidase staining method using monoclonal antibodies against H. pylori and HLA-DR antigens, were studied topographically. Fifty-nine biopsy specimens from 41 patients who had neither gastric cancer nor peptic ulcers were examined. H. pylori was observed predominantly over or on the surface epithelium, while HLA-DR antigens were frequently expressed on the epithelium of the isthmus region. These observations led to the conclusion that there was no direct topographic association between H. pylori and epithelial HLA DR expression. However, the frequency of HLA-DR expression in H. pylori-positive (28/29) specimens was significantly higher than that in H. pylori-negative (18/30) specimens (P < 0.01). Furthermore, a greater number of H. pylori was associated with a stronger expression of HLA-DR antigens (P < 0.001). We conclude that H. pylori is indirectly related to HLA-DR expression on gastric epithelium. H. pylori is the first microbial agent that has been suggested to be associated with epithelial HLA-DR expression in the human gastrointestinal tract. PMID- 7773344 TI - Diagnosis of gastric adenocarcinoma using a scoring system: combined assay of serological markers of Helicobacter pylori infection, pepsinogen I and gastrin. AB - This study was carried out to develop a scoring system for the diagnosis of gastric adenocarcinoma (GAC). A total of 686 subjects, 150 patients with GAC, 182 with gastric ulcer, 127 with duodenal ulcer, and 227 subjects with negative findings, were enrolled. Analysis of the likelihood ratio (LR) showed that patients with advanced age, ulcer in the stomach, low serum levels of pepsinogen I (PGI), low PGI x gastrin values, and low PGI/gastrin ratio were likely to have GAC. Of these indicators, the serum PGI level had the greatest weight, with a LR of 7.59 for the group with a level < 30 ng/ml. A scoring system combining serum PGI level, Helicobacter pylori seropositivity, and gastric ulcer status was derived, using a logistic regression model. This scoring system was found to be better than any one-parameter criterion for diagnosing GAC after evaluation by the area under the receiver operating characteristic curve (0.84; 95% confidence interval, 0.81-0.88) or by specificity-fixed sensitivity (sensitivity 0.82 at specificity 0.72, sensitivity 0.87 at specificity 0.66, sensitivity 0.96 at specificity 0.44). This scoring system may be potentially useful as a new model for the noninvasive diagnosis of GAC in the future. PMID- 7773345 TI - Correlation of DNA content between endoscopic biopsy and surgically resected specimens in gastric and colorectal cancer. AB - To investigate DNA heterogeneity and the consistency of DNA content between endoscopic biopsy and the corresponding resected specimens, the DNA content of 749 different samples from 30 gastric and 30 colorectal cancers was analyzed and the results were compared with those obtained from endoscopic biopsy specimens. The incidence of DNA heterogeneity was 33% in patients with gastric cancer and 40% in those with colorectal cancer. Most of the cases of heterogeneity were caused by differences in DNA indices in aneuploidy. The consistency of DNA ploidy pattern between endoscopic biopsies and the corresponding resected specimens was 100% in both gastric and colorectal cancer, while the consistency in the DNA index of aneuploid tumors was approximately 90%. From these results, it seems possible that analysis of the DNA content of a biopsy specimen could provide an adequate measure of the DNA content of the corresponding resected specimen. PMID- 7773346 TI - Epidermal growth factor enhances repair of rat intestinal mucosa damaged by oral administration of methotrexate. AB - To examine the trophic effect of epidermal growth factor on the rat small intestine, we measured diamine oxidase and ornithine decarboxylase activities in intestinal mucosa injured by methotrexate. Methotrexate was infused orally via a gastric tube at a dose of 10 mg/kg per day on 3 successive days (days 1-3). Epidermal growth factor was injected intraperitoneally at a dose of 40 micrograms/kg per day on 4 successive days following methotrexate infusion (days 4-7). Methotrexate caused a marked decrease in diamine oxidase activity; this decrease returned to a normal level on day 13 in controls. In rats injected with epidermal growth factor, diamine oxidase activity began to recover earlier than in the controls, and returned to a normal level on day 11. Epidermal growth factor enhanced the increase of ornithine decarboxylase activity in mucosa injured by methotrexate. When the increase of ornithine decarboxylase activity was suppressed by alpha-difluoromethylornithine, epidermal growth factor failed to facilitate the repair of intestinal mucosa. These results indicate that epidermal growth factor enhances intestinal repair following methotrexate infusion, and that this effect is mediated, at least in part, by ornithine decarboxylase. It is proposed that epidermal growth factor can be used clinically as a means to enhance mucosal repair of the intestine after chemotherapy with methotrexate. PMID- 7773347 TI - Significance of superoxide dismutase (SOD) in human colorectal cancer tissue: correlation with malignant intensity. AB - The significance of superoxide dismutase (SOD) activity in colorectal cancer tissue was determined from the aspect of the antioxidant defense system. SOD activity and thiobarbituric acid reactive substance were measured in the tumor, in tissues adjacent to the tumor, and in regions that appeared normal, and the results were analyzed in terms of various histopathological factors (stage of disease, depth of invasion, venous invasion, etc.). DNA ploidy pattern and cell proliferation in cancer tissue were also measured, and the results analyzed in relation to SOD activity. SOD activity in cancer tissue was higher than in the other two regions. SOD activity in cancer tissue increased with the progression of stage, and changed with the depth of invasion. There was a significant difference in SOD activity between patients with venous invasion and those in whom this was absent. Stepwise regression analysis suggested that venous invasion was the most significant factor influencing SOD activity. The proliferation index was high in cancer tissue with low SOD activity. The incidence of aneuploidy was high in cancer with high SOD activity, whereas the incidence of diploidy was high in cancer with low SOD activity. These results suggest that elucidation of the antioxidant system in cancer tissue can provide us with a better strategy for cancer treatment. PMID- 7773348 TI - Colonic mucosal hemodynamics and tissue oxygenation in patients with ulcerative colitis: investigation by organ reflectance spectrophotometry. AB - Colonic mucosal hemodynamics were investigated at the rectosigmoidal region of the colon in 46 patients with ulcerative colitis and in 18 normal subjects by organ reflectance spectrophotometry under colonoscopy. The value for the index of mucosal hemoglobin concentration (IHb) was significantly higher, and value for the index of mucosal hemoglobin oxygen saturation (ISO2) was significantly lower in patients with active ulcerative colitis than values in the normal controls or in patients with inactive ulcerative colitis. The results indicate mucosal congestion and hypoxemia in patients with active ulcerative colitis. The changes in IHb and ISO2 correlated well with the severity of ulcerative colitis scored by endoscopic findings and with the number of infiltrating inflammatory cells in the mucosa analyzed histologically in biopsy samples. In conclusion, the colonic mucosal microcirculation in patients with active ulcerative colitis was disturbed and showed congestion and hypoxemia. The analysis of hemodynamic changes may be helpful for assessing the activity of ulcerative colitis. PMID- 7773350 TI - Clinicopathologic studies of immunologic fecal occult blood test for colorectal cancer. AB - In our hospital, 83 patients with colorectal cancer underwent the immunologic fecal occult blood test (IFOBT). The positive rate for IFOBT in all patients was 87%. Colon cancers more proximal than the transverse colon were 100% positive. Carcinomas of the ulcerative type showed a significantly higher positive rate than those of the non-ulcerative type (94% vs 73%). Carcinomas penetrating the muscularis or beyond showed a significantly higher positive rate, of 96% (52/54 cases) compared to carcinomas confined to the mucosa or submucosa, which gave positive rates of 64% and 60%, respectively. In the investigation of the 7 patients with colorectal cancer who showed negative results on the IFOBT, IFOBT had been performed only once in of these patients. Accordingly, it was considered necessary to perform IFOBT more than once. The cancers in 5 of these 7 patients were found to be carcinomas confined to the mucosa. This result suggests the advisability of annual IFOBTs. It is also considered necessary to manage patients who show undefinable but possibly positive (+/-) results with caution. PMID- 7773349 TI - A study of the histological criteria for ulcerative colitis: retrospective evaluation of multiple colonic biopsies. AB - It is clinically important to distinguish idiopathic inflammatory bowel disease (IBD) from other colitides, and ulcerative colitis (UC) from Crohn's disease (CD); however only a few histological criteria based on colonic biopsies have been established. We investigated 209 consecutive series of biopsies taken from 38 patients with UC, 12 with CD, and 105 with other colitides, to evaluate whether combinations of histological features, selected on the basis of our experience, and listed below, could be useful criteria for the differential diagnosis of IBD, and, more specifically, of UC: (A) chronic inflammation with a predominant increase of plasma cells, (B) crypt distortion, (C) crypt atrophy, (D) diffuse chronic inflammation within a biopsy and between biopsies, and (E) diffuse mucin depletion within a biopsy and between biopsies. Findings that fulfilled all or two of A-C distinguished IBD from the other colitides with high sensitivity (94.3%) and specificity (95.8%). When the findings fulfilled the additional criteria of D and/or E, UC was differentiated from CD or the other colitides with high sensitivity (86.4%) and specificity (99.3%). PMID- 7773351 TI - Antibody-dependent cell-mediated cytotoxicity against cell lines generated by liver-specific idiotype-bearing antibody. AB - We produced a murine monoclonal antibody (mAb), designated H2-mAb, against a fractionated soluble phase of human liver homogenate which antibody reacted with human liver cells. A human antibody possessing the same idiotype as the H2-mAb, designated LSIA (liver-specific idiotype-bearing antibody), can be measured by a sandwich enzyme-linked immunosorbent assay, using the anti-H2 idiotype antibody. The serum level of LSIA in patients with histologically proven chronic hepatitis (CH) was significantly higher than that in healthy subjects and it was also higher than that in subjects with other diseases, including systemic lupus erythematosus. In a comparison between patients with CH type B and those with CH type C, there was no significant difference in serum levels of LSIA. It was possible to purify LSIA from the sera of patients with CH. The purified LSIA bound to the human cell lines Chang and HCC-M, derived from liver cells and a hepatoma respectively, but not to HeLa cells, a uterine carcinoma derivative. The reactivity of this mAb to HCC-M was weaker than that to Change. Moreover, the presence of LSIA caused an antibody-dependent cell-mediated cytotoxic challenge against Change cells in vitro. PMID- 7773352 TI - Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus. AB - We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems. PMID- 7773353 TI - Transcatheter arterial chemoembolization therapy with epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma. AB - The efficacy of transcatheter arterial Lipiodol chemoembolization (TALCE) using epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma (HCC) was assessed retrospectively. EMILE was confirmed to have characteristics of fair dispersibility, stability, and slow drug release in vitro prior to clinical administration. TALCE without EMILE (simple infusion of anticancer drugs and Lipiodol) and with EMILE were preoperatively performed in two groups of candidates for hepatectomy, consisting of 17 patients each (non EMILE and EMILE groups). Mean percentages of Lipiodol retention area to tumor area on computed tomographic (CT) scan following TALCE were 46.8 +/- 38.4% and 91.5 +/- 13.2% (mean +/- SD), respectively (P = 0.0005). Mean percentages of necrotic area to tumor area determined on histologic study of specimens were 42.9 +/- 43.8% and 63.2 +/- 44.0%, respectively (NS). In conclusion, TALCE with EMILE brought about longer retention of Lipiodol in HCC; however, gelatin sponge cubes and a higher dose of epirubicin hydrochloride were more significantly related to tumor necrosis than treatment with EMILE. PMID- 7773354 TI - Effects of cisapride on gallbladder emptying and pancreatic polypeptide and cholecystokinin release in humans. AB - We investigated the effects of cisapride on gallbladder motility and on the release of pancreatic polypeptide and cholecystokinin in the fasting and postprandial states. Cisapride (7.5 mg) and/or a test meal was administered intraduodenally to seven healthy volunteers with or without atropine pretreatment (0.5 mg, i.m.). In the fasting state, cisapride increased gallbladder volume to 154% of the basal level, and significantly elevated plasma pancreatic polypeptide levels. The effects of cisapride were inhibited by atropine. In the postprandial state, integrated pancreatic polypeptide and cholecystokinin responses were increased by cisapride to 180% and 192%, respectively, of control values. Atropine inhibited the integrated gallbladder and pancreatic polypeptide response to about 60% of the control value, but did not affect the cholecystokinin response. These observations suggest that: (1) fasting gallbladder tone is influenced by cholinergic inhibitory mechanisms, (2) acetylcholine (ACh) is the final mediator for about 40% of the postprandial gallbladder emptying and pancreatic polypeptide response, and (3) coordination between the ACh-independent cholecystokinin response and ACh-dependent pancreatic polypeptide response may be important in the regulation of postprandial gallbladder emptying. PMID- 7773355 TI - Endoscopic injection sclerotherapy for esophageal variceal hemorrhage in myeloproliferative disorder: case report. AB - A 70-year-old woman with myeloproliferative disorder and massive splenomegaly presented with hematemesis. Emergency endoscopy demonstrated bleeding from esophageal varices. Management of variceal hemorrhage by endoscopic injection sclerotherapy, using 5% ethanolamine oleate, was successful. Following the control of variceal bleeding, she was treated with hydroxyurea, a myelosuppressive agent. The spleen size markedly decreased and she was discharged 3 months later. Variceal hemorrhage in myeloproliferative disorder has been reported to be fatal on many occasions, despite different therapeutic approaches, including surgery. In this report, we demonstrated that endoscopic injection sclerotherapy followed by treatment with a myelosuppressive agent was effective in a patient with myeloproliferative disorder and variceal hemorrhage. PMID- 7773356 TI - A case of early gastric malignant lymphoma diagnosed and completely resected by strip biopsy. AB - A case of early gastric malignant lymphoma definitively diagnosed by strip biopsy is reported. The subsequent operation revealed that the strip biopsy had resulted in radical resection. A 55-year-old woman visited our hospital for detailed examination of a small gastric lesion. Histologic findings of the specimens obtained by conventional forceps biopsy indicated reactive lymphoid hyperplasia, although the possibility of malignant lymphoma was not completely ruled out. Strip biopsy was, therefore, performed to establish a definitive diagnosis. Histopathological examinations of the strip biopsy specimen revealed definitive findings of malignant lymphoma, which was B-cell phenotype immunocytochemically. The margin of the resected specimen was free of invasion by malignant lymphoma and no lymph node involvement was suggested by endoscopic ultrasonography, computed tomography, and gallium scintigram. Subtotal gastrectomy was subsequently performed to rule out the possibility of remaining malignant lymphoma cells. It was proven that the strip biopsy removed the lesion completely and no perigastric lymph nodes were involved. While is still controversial as to whether strip biopsy should be adopted for the radical resection of early gastric lymphoma, this procedure can definitely provide excellent specimens for the accurate diagnosis of gastric malignant lymphoma and probably for group III lesions in the stomach. PMID- 7773357 TI - A case of mesenteric venous thrombosis after endoscopic variceal band ligation. AB - A rare case of isolated superior mesenteric venous thrombosis (MVT) after endoscopic variceal band ligation (EVL) is reported. A 64-year-old woman with a history of idiopathic portal hypertension presented at the emergency room with vomiting, increasing cramping abdominal pain, and low-grade fever. She had undergone EVL for esophageal varices 4 months before and had had intermittent attacks of mild abdominal pain after the EVL. Ultrasonogram of the abdomen demonstrated marked concentric wall thickening of the ileal loop. Enhanced computed tomographic (CT) scan revealed a central lucency in the lumen of the superior mesenteric vein, surrounded by a high-density vein wall, corresponding to a thrombus. An isolated MVT and venous collateral network in the splanchnic area were confirmed by angiography. Supportive therapy, i.e., water and electrolyte replacement, and anticoagulation improved the clinical condition and radiologic status. This case of MVT after EVL suggests a possible relationship between EVL and MVT. It is necessary for clinicians to be aware of this relationship for the early diagnosis of MVT. PMID- 7773358 TI - DNA aneuploidy in a case of rectosigmoid adenocarcinoma complicated by ulcerative colitis. AB - A case of Borrmann type IV colorectal adenocarcinoma detected as a complication of long-standing ulcerative colitis is reported. Barium enema and colonoscopy disclosed a stenotic area associated with a tumoral mass and a flat elevated lesion in the rectosigmoid region and a submucosal tumor-like lesion in the rectum. Total colectomy was performed and histological studies demonstrated a moderately differentiated adenocarcinoma accompanied by high- and low-grade dysplasia. DNA ploidy pattern analysis showed aneuploidy in the adenocarcinoma and high-grade dysplasia, but diploidy in the normal and atrophic mucosa and in low-grade dysplasia. DNA aneuploid content was associated with the presence of colorectal carcinoma complicating ulcerative colitis, indicating that DNA content studies should be included in screening programs to detect early colorectal carcinoma following this disease, as a complementary study to histological assessment. PMID- 7773359 TI - A case of spindle cell sarcomatous change of hepatic ducts manifesting as obstructive jaundice. AB - Spindle cell carcinoma is a rare tumor commonly occurring in the upper aerodigestive tract. We report a 62-year-old male with spindle cell sarcomatous change located at the hepatic hilum, resulting in obstructive jaundice. The patient died after an extended resective operation. The rare disease and its histogenesis is discussed. PMID- 7773360 TI - A case of AIDS-related hepatic Kaposi's sarcoma. AB - In Japan, Kaposi's sarcoma (KS) is a very rare neoplasm. However, it does occur as one of the complications in patients with acquired immunodeficiency syndrome (AIDS). AIDS-related KS commonly involves the skin, lymph nodes, and gastrointestinal tract. Hepatic KS is sometimes observed in AIDS patients at autopsy, but it is very rarely diagnosed during life. We report a case of hepatic KS in an AIDS patient, detected by ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) during life and proven at autopsy. Abdominal US revealed multiple hyperechoic tumors along the portal vein. CT scan showed low density and delayed enhancement by contrast material. These tumors were revealed as a low intensity area on a T1-weighted image of MRI and as a high intensity area on T2-weighted and proton density images. US, CT scan, and MRI revealed characteristic findings of hepatic KS. These procedures are very useful for the diagnosis of hepatic KS. To our knowledge, this is the first report of hepatic KS in Japan. PMID- 7773361 TI - The effect of E3330 on active oxygen generation by isolated hepatic macrophages in rats. PMID- 7773363 TI - Clinical applications of two-dimensional electrophoresis. AB - Two-dimensional electrophoresis is increasingly being used as an important tool for biological research although it continues to have few direct clinical applications. In the absence of simple systems to identify and quantify individual proteins or groups of proteins it is unlikely that clinical applications will increase. Measurement of some individual proteins, for example a single acute phase reactant, often yields as much clinically useful information as could be currently expected from quantitation of several proteins with the same physiological role. Cost-containment pressures within the clinical laboratory will prevent the technique from becoming widely used in the clinical laboratory until it can clearly demonstrate that it can produce clinically important and necessary information that can not be obtained by other means. We continue to believe that the technique's greatest potential lies in identifying a protein or proteins whose concentration can be correlated with a disease and whose concentration varies with the progress of the disease. Antibodies to such proteins can then be produced and used to quantify the disease-associated proteins by a simple procedure, such as nephelometry. In spite of our belief of the likely clinical application of the technique there appears to be no systematic use of two-dimensional electrophoresis for this purpose. With clinical specimens a few investigators still run gels of serum or urine from patients with apparently unusual disorders and compare them visually with gels from healthy individuals. Nevertheless, the technique continues to have considerable unmet promise for clinical applications. PMID- 7773362 TI - Role of endothelin in the development of hemorrhagic pancreatitis in rats. PMID- 7773364 TI - Protein mutations revealed by two-dimensional electrophoresis. AB - High-resolution two-dimensional electrophoresis (2DE) can resolve many hundreds of proteins present in complex mixtures depending on the method of detection. These proteins can be characterised qualitatively, with respect to their electrophoretic mobilities (i.e. charge and apparent molecular mass) and quantitatively, using densitometry, to determine their amounts. There has been a widespread application of 2DE in the analysis and characterisation of protein mutations for a range of organisms. This review presents examples of the use of 2DE to study naturally occurring protein mutations and polymorphisms as well as the characterisation of induced protein mutations in prokaryotes and eukaryotes. Examples are presented to illustrate the use of 2DE to detect mutations affecting the electrophoretic mobility and biosynthesis of individual proteins as well as mutations leading to global alterations in cellular protein synthesis. The advantages and disadvantages of 2DE in the detection of protein mutations are discussed. PMID- 7773365 TI - Non-denaturing gel electrophoresis of biological nanoparticles: viruses. AB - Although gel electrophoresis is usually used for the fractionation of monomolecular particles, it is also applicable to the fractionation of the multimolecular complexes produced during both cellular metabolism and assembly of viruses in virus-infected cells. Gel electrophoretic procedures have been developed for determining both the size of a spherical particle and some aspects of the shape of a non-spherical particle. Capsids bound to DNA outside of the capsid can also be both fractionated and characterized. The procedures developed will be used for screening viral mutants; they also can potentially be used for diagnostic virology. Sensitivity of detection, the major current limitation, is being improved by use of both improved stains and scanning fluorimetry. The gels used for fractionation sometimes approximate random straight fiber gels, but become increasingly biphasic as the gel concentration is decreased. PMID- 7773366 TI - Polyacrylamide gel electrophoretic methods in the separation of structural muscle proteins. AB - Polyacrylamide gel electrophoresis plays a major role in analyzing the function of muscle structural proteins. This review describes one- and two-dimensional gel electrophoretic methods for qualitative and quantitative investigation of the muscle proteins, with special emphasis on determination of protein phosphorylation. The electrophoretic studies established the subunit structures of the muscle proteins, characterized their multiple forms, revealed changes in subunit composition or shifts in isoform distribution of specific proteins during development, upon stimulation or denervation of the muscle. Protein phosphorylation during muscle contraction is preferentially studied by two dimensional gel electrophoresis. The same method demonstrated protein alterations in human neuromuscular diseases. PMID- 7773368 TI - Protein separation techniques in the study of tissue regeneration. AB - The present report reviews the use of protein separation by means of two dimensional gel electrophoresis in the study of tissue regeneration. It is shown that such an approach can provide data on protein synthesis in different stages of limb regeneration or comparative data with other regenerative processes such as tail and lens regeneration. Such an approach is more realistic than other methods employing gene cloning or generation of antibodies and can lead to the actual identification and characterization of factors that are involved in these phenomena. PMID- 7773367 TI - Advances in agarose gel electrophoresis of serum lipoproteins. AB - Agarose gel electrophoresis has been extensively employed by researchers to gain a greater understanding of lipoprotein biology and its relationship to cardiovascular disease. Advances in this technique have been made in the visualization and quantitation of separated lipoproteins, in the use of agarose gel electrophoresis for detection and quantitation of apolipoproteins of the separated lipoproteins, and in the detection of lipoprotein heterogeneity. Agarose gel electrophoresis has been employed for two-dimensional electrophoretic analysis of lipoproteins as well as in several different methods which probe the immunological properties of lipoproteins. Agarose gel electrophoresis has thus become an important tool in the study of serum lipoproteins in both clinical and basic science laboratories. PMID- 7773370 TI - Education on abortion urged. PMID- 7773369 TI - Injection bias of DNA fragments in capillary electrophoresis with sieving. AB - The relative amounts of DNA fragments in a mixture injected into the capillary by electromigration or hydrodynamically by pressure were compared. Even if the electrophoretic mobilities of DNA fragments with different sizes are the same in a free solution in the sample vial, the size bias is brought about by the different mobilities in a sieving medium and by the electroosmosis. The experiments were performed in capillaries filled with a solution of liquified agarose, a replaceable sieving medium. The experimental results were compared with a theoretical model. PMID- 7773371 TI - Understanding rostering. Part 1. The rights & wrongs of rostering. PMID- 7773372 TI - The sun the moon & the stars. PMID- 7773373 TI - Competence is more than just standards. PMID- 7773374 TI - Sharing sorrow--a new beginning. PMID- 7773375 TI - The rise and fall of blood pressure measurements. PMID- 7773379 TI - Physiological roles of leupeptin and extracellular proteases in mycelium development of Streptomyces exfoliatus SMF13. AB - Streptomyces exfoliatus SMF13 produced leupeptin, chymotrypsin-like protease (CTP), metalloprotease, and trypsin-like protease (TLP) extracellularly. The activity of TLP was specifically inhibited by leupeptin. Production of leupeptin was closely associated with growth but leupeptin was inactivated by leupeptin inactivating protein (LIP) when growth reached the stationary phase in submerged cultures, or when aerial mycelia started to form on surface cultures. Autolysis of mycelia after the stationary phase in submerged cultures was apparently retarded by the addition of leupeptin; on surface cultures, aerial mycelium formation was clearly retarded by the addition of leupeptin. We propose that CTP participates primarily in utilization of a proteinaceous nitrogen source, that TLP functions as an essential enzyme involved in the metabolism of mycelial protein, that leupeptin inhibits the activity of TLP and that LIP inactivates leupeptin. The cascade of regulatory actions of the compounds, which are produced sequentially during mycelium development, may provide selective advantages in adverse culture conditions. PMID- 7773378 TI - Streptomyces peucetius daunorubicin biosynthesis gene, dnrF: sequence and heterologous expression. AB - The dnrF gene, responsible for conversion of aklavinone to epsilon-rhodomycinone via C-11 hydroxylation, was mapped in the daunorubicin (Dnr) gene cluster of Streptomyces peucetius ATCC 29050, close to drrAB, one of the anthracycline resistance genes. The dnrF gene was sequenced and should encode a protein of 489 amino acids with a molecular mass of 52 kDa. The deduced DnrF protein shows significant similarities with bacterial FAD- and NADPH-dependent hydroxylases either required to introduce hydroxyl groups into polycyclic aromatic polyketide antibiotics or involved in catabolism of aromatic compounds. Heterologous expression of dnrF in Streptomyces lividans TK23 and in Escherichia coli demonstrated that the gene encodes a NADPH-dependent hydroxylase catalysing the hydroxylation of aklavinone to yield epsilon-rhodomycinone. The enzyme is inactive on anthracyclines glycosylated at position C-7 and its activity decreases to a different extent with other substrate modifications, indicating that DnrF has a significant substrate specificity. PMID- 7773380 TI - Lactococcus lactis glyceraldehyde-3-phosphate dehydrogenase gene, gap: further evidence for strongly biased codon usage in glycolytic pathway genes. AB - The gene gap, encoding glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), was isolated from a genomic library of Lactococcus lactis LM0230 DNA. Plasmids containing the L. lactis gene were able to complement a gap mutant of Escherichia coli. The nucleotide sequence of gap predicted a polypeptide chain of 337 amino acids for the enzyme and a subunit molecular mass of 36,043. The codon usage in gap and four other glycolytic genes from L. lactis showed a high degree of bias, when compared with 84 other chromosomal genes. Northern blot analysis of total L. lactis RNA showed that gap hybridized strongly with a 1.3 kb transcript. The 5' end of the transcript was determined by primer extension analysis to be a C located 35 bp upstream from the gap start codon. These transcript analyses, and the orientation of the open reading frames in the DNA flanking gap, indicated that in L. lactis gap is expressed on a monocistronic transcript. Nucleotide sequencing indicated that the DNA adjacent to gap did not encode other glycolytic pathway enzymes. The DNA sequence flanking gap contained two open reading frames (ORF156 and ORF211) of unknown function. The 3' end of a clpA homologue was identified in the sequence upstream of ORF156. The location of gap on the L. lactis DL11 chromosome map was determined to be between map coordinates 0.530 and 0.660. PMID- 7773381 TI - Biochemical genetics of a natural population of Escherichia coli: seasonal changes in alleles and haplotypes. AB - The level of diversity, degree of enzyme polymorphism, effective population size, and the relative roles of drift and selection were examined in a cross-section of a natural Escherichia coli population based on random samples of haplotypes of E. coli isolated from sewage. The population studied contained E. coli strains derived from a human population of approximately 16,000 individuals, as well as from other sources. Three sample sets were taken between May and August. Each set consisted of 100 E. coli clones. Six enzyme loci [GPI (5 alleles), GPD (5 alleles), PGD (10 alleles), ADH (8 alleles), IDH (6 alleles), PGM (6 alleles)] were surveyed electrophoretically for each clone; 159 different haplotypes were obtained and it is likely that all possible combinations are present in the population sampled. The large numbers of different haplotypes observed were distributed as a series of four genetically similar families of clones. The large estimated effective population size (Ne = 10(10)) means that the observed large and highly significant changes in allele frequencies with time are not due to genetic drift. Selection, though not necessarily at the loci studied, is considered the only likely explanation. PMID- 7773382 TI - Mercury resistance as a selective marker for recombinant mycobacteria. AB - The use of antibiotic-resistance markers for the selection of recombinant mycobacteria is widespread but questionable considering the development of live recombinant BCG vaccines. In contrast, vector-encoded resistance to heavy metals such as mercury may represent an interesting alternative for the development of live vaccines compatible with use in humans and in animals. The mercury resistance genes (mer) from Pseudomonas aeruginosa and from Serratia marcescens were cloned into the Escherichia coli-Mycobacterium shuttle vector pRR3. The resulting vectors, designated pMR001 and pVN2, were introduced by electroporation into Mycobacterium smegmatis, Mycobacterium bovis BCG and Mycobacterium tuberculosis. The recombinant mycobacteria were stable in vitro and in vivo, and had high-level mercury resistance, thus indicating that the mer genes can be useful as selective markers in mycobacteria. PMID- 7773383 TI - Molecular biology of aflatoxin biosynthesis. PMID- 7773384 TI - Trichoderma harzianum genes induced during growth on Rhizoctonia solani cell walls. AB - Trichoderma harzianum is a biocontrol agent that attacks a range of economically important phytopathogenic fungi. In an attempt to identify genes specifically expressed by T. harzianum during growth on cell walls of Rhizoctonia solani, we carried out differential screening of an induced cDNA library. In this paper we report the analysis of the sequence and expression of two cDNA clones that encode putative mycoparasitism-related proteins of T. harzianum. One of these clones corresponds to a gene, inda1, that encodes a protein of 570 amino acids with a predicted molecular mass of 62,853 Da. The predicted amino acid sequence of inda1 showed a high degree of similarity with amino acid permeases from several other organisms. The other cDNA clone corresponds to a gene, indc11, that encodes a novel protein of 340 amino acids with a predicted molecular mass of 37,010 Da. The use of this methodology should provide specific genetic markers to follow mycoparasitism by Trichoderma spp. PMID- 7773385 TI - A basic serine protease from Paecilomyces lilacinus with biological activity against Meloidogyne hapla eggs. AB - Scanning electron micrographs of the nematode-egg-parasitic fungus Paecilomyces lilacinus infecting eggs of the root-knot nematode Meloidogyne spp. suggested the involvement of lytic enzymes. When grown on a liquid mineral salts medium, supplemented with different substrates as the sole N- and C-source, the fungus produced an extracellular protease. Colloidal chitin, vitellin and intact eggs of the root-knot nematode Meloidogyne hapla induced proteolytic activity that was repressed by glucose. The protease was partially purified from the culture filtrate by affinity chromatography. It has a molecular mass of 33.5 kDa, a pH optimum of 10.3, a temperature optimum of 60 degrees C and an isoelectric point above pH 10.2. The enzyme was completely inhibited by PMSF. The amino acid sequence, as derived from the nucleotide sequence of a cDNA clone, had high homology with several subtilisin-like serine proteases. It was shown that the purified enzyme degrades vitellin. The protease quantitatively bound to nematode eggs, and eggs incubated with the purified protease eventually floated. Incubation of the purified protease with nematode eggs significantly influenced their development as demonstrated by time-lapse microscopy. Immature eggs were highly vulnerable to protease treatments, whereas those containing a juvenile were more resistant. In addition, hatched larvae were not visibly affected by the protease. It can be concluded that the serine protease might play a role in penetration of the fungus through the egg-shell of nematodes. PMID- 7773387 TI - Inducible expression of heterologous genes targeted to a chromosomal platform in the cyanobacterium Synechococcus sp. PCC 7942. AB - High-level, inducible expression of heterologous genes in the cyanobacterium Synechococcus sp. strain PCC 7942 was obtained using the Escherichia coli trc promoter and lacI repressor. The petE gene of Anabaena sp. strain PCC 7937 encoding plastocyanin precursor protein and the E. coli uidA gene encoding beta glucuronidase were initially placed under the control of the trc promoter and lacI repressor by cloning into the E. coli pTrc99C expression vector and were introduced into the chromosomal platform for integration in metF (PIM) of the Synechococcus R2-PIM9 recipient strain. These pTrc99C-derived constructs often gave rise to transformants that did not contain a complete insert gene, probably because of gene conversion events. Selection of the desired Synechococcus R2-PIM9 transformants was vastly improved using the new pTrcIS vector that contains the aadA gene encoding streptomycin resistance as an extra antibiotic resistance marker. The influence of IPTG concentration and induction time on gene expression with the E. coli trc/lacI system in Synechococcus was determined using beta glucuronidase as a reporter. The Anabaena PCC 7937 petE gene in Synechococcus was expressed to a high level upon induction with IPTG as shown by RNA and immunoblot analysis. The general usability of pTrcIS as a cloning vector for inducible heterologous gene expression in Synechococcus was confirmed by the introduction of several more genes. PMID- 7773386 TI - Characterization of npf mutants identifying developmental genes in Physarum. AB - In Physarum polycephalum, uninucleate haploid amoebae develop into macroscopic multinucleate plasmodia. Wild-type, sexual development is triggered when two amoebae carrying different alleles of matA fuse to form a zygote which develops into a diploid plasmodium. Mutations in the matA genetic region give rise to apogamic strains in which a single haploid amoeba can develop into a haploid plasmodium. An essential stage in both sexual and apogamic plasmodium formation is an extended cell cycle in uninucleate cells, which ends with the formation of a binucleate cell by mitosis without cytokinesis. Using a 'brute force' screening method, we have isolated mutants blocked in apogamic plasmodium development. Genetic analysis showed that the mutations we have identified were unlinked to matA, unlike mutations previously identified following an enrichment step. Most of the loci revealed by our screen were represented by only one allele, indicating that further screening should lead to the identification of additional genes required for plasmodium development. Phenotypic analysis showed that different mutants were blocked at different stages of plasmodium formation. Some of the mutations blocking apogamic development at an early stage, close to the start of the long cell cycle, failed to block sexual development in zygotes homozygous for the mutation. Since the two modes of plasmodium formation differ only in the initiation of development, these mutations presumably interfere with the initiation process. In the remaining mutants, in which both sexual and apogamic development were blocked, development first became abnormal towards the end of the long cell cycle. This suggested that the wild-type gene products were required by this time and was consistent with previous evidence that many changes in cellular organization and gene expression occur during the long cell cycle. Each of these mutants showed a different terminal phenotype and some aspects of plasmodium development occurred normally although others were blocked, suggesting that development involves multiple pathways rather than a dependent sequence of events. Phenotypic analysis of double mutants supported this conclusion and also revealed epistatic interactions, presumably due to blocks in the same pathway. In several of the mutants, terminally differentiated cells died by an apoptosis-like mechanism; since this was never observed in vegetative cells, it was presumably triggered by the failure of development. Phenotypic analyses of additional mutants will extend our understanding of the pathways involved in plasmodium development. PMID- 7773388 TI - IS292: a novel insertion element from Agrobacterium. AB - A new insertion sequence, IS292, located in the 6b gene of a nopaline-type Agrobacterium strain (X88-292) isolated from poplar was identified and sequenced. IS292 is 2494 bp long, has 21 bp inverted terminal repeats with two mismatches, and generates 10 bp direct repeats upon integration. No sequence similarity was found between IS292 and other insertion elements associated with Agrobacterium, but it shows strong similarity with ISR/1 from Rhizobium leguminosarum bv. viciae. The occurrence of IS292-like sequences in various Agrobacterium isolates, especially different Agrobacterium strains isolated from the same biotope, was demonstrated by DNA hybridization. PMID- 7773389 TI - Flavohaemoglobin HmpX: a new pathogenicity determinant in Erwinia chrysanthemi strain 3937. AB - Unlike wild-type Erwinia chrysanthemi strain 3937, which fully macerates inoculated Saintpaulia plants, HmpX- mutants produce necrotic lesions or no symptoms. The hmpX gene was sequenced and the corresponding protein sequence analysed. We show that HmpX belongs to a family of flavohaemoproteins (HMP), previously identified in two yeasts and in Escherichia coli. Comparisons of protein sequences at the secondary structure level by hydrophobic cluster analysis have shown that HmpX possesses two functional regions, a haemoglobin domain in its N-terminal part and a flavin reductase domain in its C-terminal part. In an HmpX- strain, the synthesis of pectate lyases, which are pathogenicity determinants in E. chrysanthemi, was reduced in conditions of low oxygen tension. Using gus fusion in hmpX, it was shown that hmpX transcription was induced in coculture with tobacco cells. A putative function for HmpX is discussed. PMID- 7773390 TI - Synergism between Erwinia pectate lyase isoenzymes that depolymerize both pectate and pectin. AB - Phytopathogenic Erwinia bacteria cause tissue maceration by secretion of pectinolytic enzymes such as pectate lyase (PL). Sequencing of overlapping genomic fragments from Erwinia carotovora subsp. atroseptica established the organization of a 7.5 kbp region encoding PL isoenzymes. Two intergenic regions of 656 and 645 bp separate three enzyme coding regions of 1125 bp exhibiting approximately 80% positional identity. The promoters of each of the three genes contain a segment with high homology to the binding sequence of the E. chrysanthemi KdgR transcription repressor, implying similar mechanisms of gene regulation in the two bacterial species. Separate expression of the pel genes in the Escherichia coli-pT7-7 system and purification of their products yielded PLs at 7-33 mg (I culture)-1 with greater than 95% purity. Availability of the recombinant enzymes allowed determination of the kinetic differences amongst the PL isoforms, PL1, PL2 and PL3. The results show that PL is not strictly confined to depolymerization of pectate since each isoenzyme more readily degrades 31% esterified pectin. Addition of isoenzyme combinations revealed no synergism with respect to degradation of pectate or 31% esterified pectin. However, addition of enzyme combinations containing PL3 enhanced the activity towards 68% esterified pectin, against which individual PL activities were low, by up to 64%. These data suggest that the combination of PL isoenzymes extends the range of pectic substrates which the bacterium can degrade. PMID- 7773391 TI - A temperature-compensated ultradian clock ticks in Schizosaccharomyces pombe. AB - An ultradian oscillation is described for Schizosaccharomyces pombe which meets the criteria for a cellular clock, i.e. timekeeping device. The rhythm can be induced by transfer from circadian conditions (stationary phase or very slow growth) to ultradian conditions (rapid growth). It can also be synchronized by ultradian temperature cycles of 6 degrees C difference. Released to constant temperature, the rhythm persists for 20 h without damping. The period of the free running rhythm is temperature-compensated and in no experiment did period length fall outside the narrow range between 40 and 44 min. The parameter observed is the septum index, i.e. the percentage of cells occupying the last stage of the cell cycle in wild-type cells before final division. The results suggest control of the cell division processes by the ultradian clock. PMID- 7773392 TI - Disruption of the actin cytoskeleton in budding yeast results in formation of an aberrant cell wall. AB - A temperature-sensitive, conditionally lethal actin mutant of Saccharomyces cerevisiae, DBY 1693, was used to study, using light and electron microscopy, dysfunction of the actin cytoskeleton in the morphogenesis of the cell wall. Cells of this mutant strain survived at least 24 h at the restrictive temperature (37 degrees C). These cells showed isodiametric growth. Mutant cells accumulated vesicles, probably as a consequence of chaotic secretory transport caused by loss of polarity. A conspicuous morphological response to the dysfunction of actin was the formation of an aberrant wall over the whole surface of the isodiametrically growing cell. This wall was of loose texture with protruding glucan microfibrils incompletely masked with amorphous matrix. It resembled the regenerating cell wall on the surfaces of yeast protoplasts. The localization of wall synthesis over the whole surface of temperature sensitive actin mutant cells was in accordance with an even distribution of submembranous actin in the form of patches (similarly to regenerating protoplasts). Delocalization of finger-like invaginations of the plasma membrane from the bud region to the whole surface of the growing cell was also found in mutant cells. PMID- 7773393 TI - Phylogenetic analysis of the ballistosporous anamorphic genera Udeniomyces and Bullera, and related basidiomycetous yeasts, based on 18S rDNA sequence. AB - The small subunit nuclear ribosomal DNA (18S rDNA) sequence was determined for twelve species of basidiomycetous anamorphic yeasts, i.e. three species of Udeniomyces, seven species of Bullera, Cryptococcus albidus and Phaffia rhodozyma. For phylogentic analysis, these sequences were aligned with published sequences for 36 other fungal species. Molecular phylogenetic analysis of maximum likelihood and parsimony showed that the 44 species of basidiomycetes analysed were divided into three major lineages. The ballistosporous yeast genera Udeniomyces and Bullera were clearly separated. On the phylogenetic tree, Udeniomyces megalosporus, U. puniceus and U. piricola showed a very close relationship with one another, and composed a lineage with Mrakia frigida, P. rhodozyma and Cystofilobasidium capitatum at high bootstrap confidence level. On the other hand, eight species of Bullera made lineages with selected species of Tremella (Tremellaceae), Filobasidium and Filobasidiella (Filobasidiaceae), Cryptococcus albidus and Trichosporon cutaneum. The molecular phylogeny deduced from the 18S rDNA sequence showed a possibility of heterogeneity among the species of Bullera at the generic level. PMID- 7773394 TI - Missense mutations that alter the DNA-binding domain of the MtrR protein occur frequently in rectal isolates of Neisseria gonorrhoeae that are resistant to faecal lipids. AB - Resistance of Neisseria gonorrhoeae to structurally diverse hydrophobic agents (HAs) has been associated with missense or deletion mutations in the mtrR (multiple transferable resistance Regulator) gene of laboratory-derived strains but their prevalence in clinical isolates was heretofore unknown. Since faecal lipids provide strong selective pressure for the emergence of variants resistant to HAs (HAR), the nucleotide sequence of the mtrR gene from rectal isolates of N. gonorrhoeae, which displayed different levels of HAR, was determined. Compared to the mtrR gene possessed by the HA-sensitive strain FA19, each clinical isolate contained mutations in the coding and/or promoter regions of their mtrR gene. A missense mutation in codon 45 (Gly-45 to Asp) was the most common mutation found in the strains studied and impacted the structure of the helix-turn-helix domain of the MtrR protein thought to be important in DNA-binding activity. Two clinical isolates bearing a missense mutation in codon 45 also contained a single basepair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region. Introduction of mtrR sequences amplified from the clinical isolates into strain FA19 revealed that acquisition of the single basepair deletion was correlated with high level HAR while mutations in the mtrR-coding region provided for an intermediate level of HAR. PMID- 7773395 TI - Plasmids pIP419 and pIP421 from Bacteroides: 5-nitroimidazole resistance genes and their upstream insertion sequence elements. AB - The genetic organization of two different 5-nitroimidazole (5-Ni) resistance genes was investigated: nimC and nimD from Bacteroides plasmids pIP419 and pIP421, respectively. The nimC gene (492 bp) and the nimD gene (495 bp) directed the synthesis of polypeptides with deduced molecular masses of 18.37 kDa and 18.48 kDa, respectively. The predicted proteins showed 67-83% identity and 78-91% similarity with the products of two other nimA and nimB genes previously described and could be derived from a common ancestral gene. An insertion sequence element (IS1170) was identified upstream of the nimC gene. IS1170 is 1604 bp in length and is flanked by imperfect inverted repeats (15 bp). IS1170 is similar to the Bacteroides insertion sequence element IS942 with an identity of 70% at the nucleotide level. The single copy of IS1170 present on plasmid pIP419 is integrated 24 bp upstream of the initiation codon of nimC. Similar genetic organization was found on plasmid pIP421. One copy of another insertion sequence (IS1169) was found 4 bp upstream of the first ATG codon of the nimD gene. This element (1325 bp) shows a strong homology at the nucleotide level (70% identity) with IS1186 and IS1168 found to be associated with the Bacteroides carbapenem resistance gene cfiA, and the 5-Nirgenes nimA and nimB, respectively. There is strong evidence that, as in the case of the cfiA gene, the transcription of the four nim genes so far studied is directed by outward-oriented promoters, carried on the right ends of the different insertion sequence elements. PMID- 7773396 TI - Variation in the size of the repeat region of the fibrinogen receptor (clumping factor) of Staphylococcus aureus strains. AB - The ability of Staphylococcus aureus to bind to fibrinogen and fibrin is believed to be an important factor in the initiation of foreign body and wound infections. Recently, the gene encoding the fibrinogen receptor (clumping factor, ClfA) of S. aureus strain Newman was cloned and sequenced. The ClfA protein possesses a highly unusual 308 residue dipeptide repeat region composed predominantly of Asp and Ser. Polymerase chain reaction analysis of seven different strains showed that the size of the clfA repeat coding region varies from 580 bp to 1320 bp. In contrast, the clfA region A is the same size in each strain. The size of the clfA repeat region did not correlate with the ability of these strains to form clumps in a solution of fibrinogen. Indeed, the strain with the smallest repeat size of 580 bp clumped almost as well as strain Newman. Each strain of S. aureus examined contained several high molecular mass proteins that reacted with anti-ClfA region A antibody. In some cases the molecular mass of the major protein varied in accordance with the length of the coding sequence for the repeat region R. PMID- 7773397 TI - Filling the gap between hns and adhE in Escherichia coli K12. AB - As a consequence of the absence of a general coordination process in the sequencing of the Escherichia coli K12 genome, to completely sequence the genome in a reasonable time it is important to fill in gaps between known regions. We report the sequence of the hns-adh region, at 27 min on the genome. PMID- 7773398 TI - Novel phosphotransferase system genes revealed by bacterial genome analysis--a gene cluster encoding a unique Enzyme I and the proteins of a fructose-like permease system. AB - Previous publications have demonstrated the presence of a cryptic gene encoding a novel Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). Recent Escherichia coli genome sequencing revealed a gene (ptsA) encoding a new Enzyme I homologue in the 89.1-89.3 centisome region. We have analysed this region, and here describe and characterize open reading frames (ORFs) encoding (1) a fused PTS Enzyme I-IIAFru homologue, (2) a glycerol dehydrogenase, (3) a transaldolase homologue, (4) two PTS IIBFru homologues, (5) a PTS IICFru homologue, and (6) homologues of pyruvate formate-lyase and its activating enzyme. Binary comparison scores, multiple alignments and phylogenetic trees establish the families of proteins to which each of the relevant ORFs belong. Identification of the putative products of this gene cluster leads to the proposal that several of the proteins encoded in this region function in anaerobic carbon metabolism. PMID- 7773399 TI - The bceT gene of Bacillus cereus encodes an enterotoxic protein. AB - A toxin gene (bceT) on a 2.9 kb DNA fragment of Bacillus cereus B-4ac was cloned and expressed in Escherichia coli, and its nucleotide sequence determined. The DNA fragment contained an open reading frame capable of encoding a polypeptide of 336 amino acids with a molecular mass of 41039 Da. The translated product in E. coli exhibited Vero cell cytotoxicity, and was positive in a vascular permeability assay. It also caused fluid accumulation in a ligated mouse ileal loop and was lethal to mice upon injection. These biological activities are considered characteristic of diarrhoeal enterotoxins. We therefore conclude that this gene, designated bceT, encodes one of the enterotoxic proteins of B. cereus which cause food-borne diarrhoea. PMID- 7773400 TI - The biosynthesis of periplasmic electron transport proteins in methylotrophic bacteria. PMID- 7773401 TI - Crystalline surface protein of Peptostreptococcus anaerobius. AB - The surface ultrastructure of three anaerobic Gram-positive cocci frequently encountered in oral infections, Peptostreptococcus micros, P. magnus and P. anaerobius, was studied. The type strains of P. micros (DSM 20468) and P. anaerobius (ATCC 27337), several clinical isolates of both species and the type strain of P. magnus (DSM 20470) were included. Thin-sectioned cells studied by electron microscopy revealed a homogeneous layer outside the peptidoglycan layer in P. anaerobius. In P. micros and P. magnus a more amorphous layer was present. No periodic structures were seen in negatively stained whole cells of these three species. However, in freeze-etched cells of P. anaerobius a crystalline surface protein layer (S-layer) was detected. No periodicity was seen in any of the P. micros strains or the P. magnus type strain by the methods used, but a periodic pattern was observed in negatively stained specimens of cell wall fragments of sonicated P. anaerobius cells. No capsular material was visible outside the S layer in P. anaerobius. The cells of the Peptostreptococcus spp. were extracted for 30 min with detergents and urea. One per cent SDS and M urea both extracted a major 78 kDa protein from all strains of P anaerobius. Extraction of P. micros and P. magnus cells did not reveal any major protein bands comparable to that of P. anaerobius. Surface biotinylation of cells followed by Western blotting and detection by alkaline-phosphatase-conjugated extravidin showed strong staining of the 78 kDa band in P. anaerobius, further indicating that this molecule is located on the surface of the cell and is the S-protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773402 TI - An inner cell wall protein (cwp1) from conidia of the entomopathogenic fungus Beauveria bassiana. AB - Following the removal of the rodlet layer from aerial or submerged conidia of the entomopathogenic deuteromycetous fungus Beauveria bassiana, SDS-insoluble, formic acid-extractable proteins were found in the residual cell wall material. Two major proteins (12.8 and 14.0 kDa) were extracted with formic acid from fractured aerial and submerged conidia but not from blastospores. Oxidation of the sample extracted by formic acid resulted in a single protein band (15.4 kDa) as judged by SDS-PAGE. Antibodies against this cell wall protein (cwp1) did not cross-react with cell wall extracts from the entomopathogenic deuteromycetous fungi Verticillium lecanii or Metarhizium anisopliae. Western blot analysis of two dimensional gels revealed at least three acidic isoforms (pI 4.0-4.8) of cwp1. Immunohistological studies revealed that the cwp1 was primarily localized in the cell wall of aerial and submerged conidia but not in blastospores. Immunolocalization was possible only if the conidia were previously boiled in 5% (v/v) beta-mercaptoethanol. The N-terminal sequence of cwp1 showed no similarities with other published sequences. Our results suggest that at least two major species of SDS-insoluble, formic-acid-extractable proteins exist in cell walls of B. bassiana aerial or submerged conidia; one is the hydrophobin which occurs in the outermost rodlet layer and the other, cwp1, occurs primarily next to the rodlet layer. PMID- 7773403 TI - Division-inhibition capacity of penicillin in Escherichia coli is growth-rate dependent. AB - Growing bacteria are sensitive to various beta-lactam derivatives due to their interference with peptidoglycan biosynthesis. At low concentrations, penicillin G (benzylpenicillin) blocks cell division without affecting mass growth rate. The MIC for division of Escherichia coli B/r (H266) was found to depend on the growth rate, which was modified by the nutritional conditions. Our hypothesis, that division sensitivity is proportional to the rate of peptidoglycan synthesis for septum formation, as well as to cell circumference, was thus confirmed. PMID- 7773404 TI - The signal transducer encoded by ampG is essential for induction of chromosomal AmpC beta-lactamase in Escherichia coli by beta-lactam antibiotics and 'unspecific' inducers. AB - Chemical mutagenesis of the AmpC beta-lactamase-hyperinducible Escherichia coli strain SN0301/pNu305 carrying the cloned ampC and ampR genes from Citrobacter freundii OS60 gave four independent mutants in which beta-lactamase was no longer inducible, or was inducible only to a low level, by beta-lactam antibiotics. The genes ampC, ampR, ampD and ampE, which were essential for beta-lactamase induction, were functional in these mutants. In all four mutants, the sites of mutation were mapped to 9.9 min on the E. coli chromosome. Complementation with wild-type ampG restored inducibility of beta-lactamase to wild-type levels. The nucleotide sequence of all four mutant ampG alleles (ampG1, ampG3, ampG4 and ampG5) was determined. In three of the mutants, a single base exchange led to an amino acid change from glycine to aspartate at different sites in the deduced amino acid sequence. In the fourth mutant (ampG4), with low-level inducibility, the nucleotide sequence was identical to wild-type ampG. Spontaneous back mutation of the chromosomal ampG1 mutant resulted in restoration of wild-type inducibility and a return to the wild-type ampG sequence. Unspecific induction by components of the growth medium was also dependent on intact ampG function. PMID- 7773405 TI - Nitrogen-regulated transcription and enzyme activities in continuous cultures of Saccharomyces cerevisiae. AB - Variations in the transcription of nitrogen-regulated genes and in the activities of nitrogen-regulated enzymes of the yeast Saccharomyces cerevisiae were studied by changing the carbon and nitrogen fluxes. S. cerevisiae was grown in continuous culture at various dilution rates (D) under nitrogen limitation with NH4Cl as sole nitrogen source. With an increase in D from 0.05 to 0.29 h-1, both the glucose and the ammonia flux increased sixfold. The activities of the two ammonia incorporating enzymes, NADPH-dependent glutamate dehydrogenase (NADPH-GDH) and glutamine synthetase (GS), encoded by GDH1 and GLN1, respectively, increased with increasing D, while the activity of the glutamate-degrading enzyme, NAD-dependent glutamate dehydrogenase (NAD-GDH), decreased. Surprisingly, no changes were observed in the transcription of GDH1 and GLN1; however increased D was accompanied by an increase in GAP1 transcription. At the metabolite level, the increase in the glucose and nitrogen flux did not result in changes in the intracellular 2-oxoglutarate, glutamate or glutamine concentrations. It is shown that growth on ammonia alone is not sufficient to cause repression of GAP1 and GLN1 transcription and that the regulation of GAP1 transcription and both NADPH GDH and GS activity is not an on/off switch, but is gradually modulated in correlation with the ammonia concentration. PMID- 7773407 TI - Evidence for a developmentally regulated prespore-specific glutamine synthetase in the cellular slime mould Dictyostelium discoideum. AB - The enzyme glutamine synthetase (GS) is described for the first time in Dictyostelium discoideum. The appearance of this enzyme is developmentally regulated. The level of activity is low in vegetative cells and increases more than threefold during differentiation. Furthermore this enzyme is shown to be differentially localized in prespore cells, the specific activity being approximately fourfold higher than in prestalk cells. The enzyme has a pH optimum of 7.8 and 8.2 in the gamma-glutamyltransferase and gamma-glutamylsynthetase assays, respectively, and a temperature optimum of 45 degrees C. Kinetic studies of GS revealed apparent Km values of 5.9 mM, 0.009 mM and 8.6 mM for glutamine, ADP and NH2OH, respectively, in the gamma-glutamyltransferase assay, and of 2.2 mM, 0.12 mM and 0.64 mM for glutamate, ATP and NH2OH, respectively, in the gamma glutamylsynthetase assay. PMID- 7773406 TI - Manipulation of intracellular glycerol and erythritol enhances germination of conidia at low water availability. AB - The insect pathogens Beauveria bassiana, Metarhizium anisopliae and Paecilomyces farinosus can be effective biocontrol agents when relative humidity (RH) is close to 100%. At reduced water availability, germination of propagules, and therefore host infection, cannot occur. Cultures of B. bassiana, M. anisopliae and P. farinosus were grown under different conditions to obtain conidia with a modified polyol and trehalose content. Conidia with higher intracellular concentrations of glycerol and erythritol germinated both more quickly and at lower water activity (aw) than those from other treatments. In contrast, conidia containing up to 235.7 mg trehalose g-1 germinated significantly (P < 0.05) more slowly than those with an equivalent polyol content but less trehalose, regardless of water availability. Conidia from control treatments did not germinate below 0.951-0.935 aw (identical to 95.1-93.5% RH). In contrast, conidia containing up to 164.6 mg glycerol plus erythritol g-1 germinated down to 0.887 aw (identical to 88.7% RH). These conidia germinated below the water availability at which mycelial growth ceases (0.930-0.920 aw). Germ tube extension rates reflected the percentage germination of conidia, so the most rapid germ tube growth occurred after treatments which produced conidia containing the most glycerol and erythritol. This study shows for the first time that manipulating polyol content can extend the range of water availability over which fungal propagules can germinate. Physiological manipulation of conidia may improve biological control of insect pests in the field. PMID- 7773408 TI - The tylosin producer, Streptomyces fradiae, contains a second valine dehydrogenase. AB - A second NAD-dependent valine dehydrogenase (VDH) of Streptomyces fradiae was detected and purified to homogeneity by affinity chromatography on Reactive-Blue 2 Sepharose followed by gel filtration and Mono Q fast protein liquid chromatography. The relative molecular masses of the native enzyme and its subunits were determined to be 80,000 and 41,000, respectively, indicating that the enzyme is a homodimer. The enzyme was the only active VDH in S. fradiae; its activity was significantly induced by L-valine, but was repressed by ammonia. Among branched- and straight-chain amino acids that serve as enzyme substrates, L 2-aminobutyrate and L-valine are preferred. Significant activities were found with deamino-NAD+ and 3-pyridinealdehyde-NAD+. The molecular and catalytic properties of the enzyme distinguish it from the enzyme previously purified, and thus indirectly indicate the existence of two VDHs in S. fradiae. PMID- 7773409 TI - Cloning of a Candida albicans peptide transport gene. AB - A Candida albicans peptide transport gene, CaPTR2, was cloned from a C. albicans genomic library by functional complementation of a peptide transport deficient mutant (strain ptr2-2) of Saccharomyces cerevisiae. CaPTR2 restored peptide transport to transformants as determined by uptake of radiolabelled dileucine, growth on dipeptides as sources of required amino acids, and restoration of growth inhibition by toxic peptides. Plasmid curing experiments demonstrated that the peptide transport phenotype was plasmid borne. CaPTR2 was localized to chromosome R of C. albicans by contour-clamped homologous electric field gel chromosome blots. Deletion subclones and frameshift mutagenesis were used to narrow the peptide transport complementing region to a 5.1 kb DNA fragment. DNA sequencing of the complementing region identified an ORF of 1869 bp containing an 84 nucleotide intron. The deduced amino acid sequence predicts a protein of 70 kDa consisting of 623 amino acids with 12 hydrophobic segments. A high level of identity was found between the predicted protein and peptide transport proteins of S. cerevisiae and Arabidopsis thaliana. This study represents the first steps in the genetic characterization of peptide transport in C. albicans and initiates a molecular approach for the study of drug delivery against this pathogen. PMID- 7773410 TI - Involvement of ArgR and PepA in the pairing of ColE1 dimer resolution sites. AB - Dimer formation and associated copy number depression is an important cause of multicopy plasmid instability. Natural multicopy plasmids employ site-specific recombination to convert dimers to monomers, thus maximizing the number of independently segregating molecules at cell division. Resolution of dimers of Escherichia coli plasmid ColE1 requires the plasmid cer site and at least four chromosome-encoded proteins: the XerC and XerD recombinases, and accessory factors ArgR and PepA. It has been suggested that ArgR has a role in the initial pairing of recombination sites and we describe here an attempt to detect this process in vivo. Our approach exploits a previous observation that a cer-like site known as the type II hybrid supports inter-molecular recombination and causes extensive multimerization of plasmids. We report that type-II-mediated multimerization can be repressed by a cer site in cis or in trans and propose that this is due to a physical interaction between the sites. If this hypothesis is correct, suppression of multimer formation provides an assay of site pairing. Our results demonstrate that the putative pairing interaction is independent of the topological relationship of the sites and that both PepA and ArgR are involved. Although most recombination-deficient mutant derivatives of ArgR are unable to pair recombination sites, we have found two (ArgR110 and ArgR115) which retain pairing activity. The validity of the pairing hypothesis is discussed in the light of alternative explanations for our data. PMID- 7773411 TI - Phage infection, transfection and transformation of Mycobacterium avium complex and Mycobacterium paratuberculosis. AB - Mycobacterium avium complex strains and Mycobacterium paratuberculosis are closely related intracellular pathogens affecting humans and animals. M. avium complex infections are a leading cause of morbidity and mortality in AIDS patients, and M. paratuberculosis is the agent of Johne's disease in ruminants. Genetic manipulation of these micro-organisms would facilitate the understanding of their pathogenesis, the construction of attenuated vaccine strains and the development of new drugs and treatment methods. This paper describes the replication of mycobacterial shuttle phasmids and plasmids, and the expression of the firefly luciferase reporter gene in M. avium complex and M. paratuberculosis. The mycobacteriophage TM4 propagated on M. smegmatis or M. paratuberculosis plaqued at the same efficiency on these two mycobacterial hosts. Screening of M. avium complex and M. paratuberculosis clinical isolates with TM4-derived luciferase reporter phages demonstrated that the majority of these isolates were susceptible to TM4. Conditions for introduction of DNA were determined by transfection of M. paratuberculosis with TM4 DNA and applied to isolate kanamycin resistant transformants of M. avium complex and M. paratuberculosis with Escherichia coli-Mycobacterium shuttle plasmids. Recombinant plasmids were recovered from transformants without apparent loss of DNA sequences. These results provide the basis for the genetic manipulation of these pathogenic mycobacterial species. PMID- 7773412 TI - Organization of carbamoyl-phosphate synthase genes in Neisseria gonorrhoeae includes a large, variable intergenic sequence which is also present in other Neisseria species. AB - The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a heterodimer, encoded by genes commonly called carA and carB. In most prokaryotes examined, these genes are separated by up to 24 bp and are cotranscribed. In Pseudomonas aeruginosa, carA and carB are also co-transcribed, but are separated by 682 bp. We have determined the complete DNA sequence of the carA and carB genes of Neisseria gonorrhoeae strain CH811. carA (1125 bp) and carB (3237 bp) are similar in size and sequence to other prokaryotic CPS genes, however they are separated by an intervening sequence of 3290 bp which has no similarity to the intervening sequence between other CPS genes; furthermore, putative transcription terminators are found downstream of both carA and carB. Several neisserial repetitive sequences were identified within the 9 kb sequenced, as well as novel 120 and 150 bp repeats (designated RS6 and RS7, respectively) which were found within the intervening sequence between carA and carB. To determine whether the intervening sequence observed in N. gonorrhoeae CH811 was not unusual, the sequence between carA and carB was amplified by PCR from 30 isolates of N. gonorrhoeae. The intervening sequence was found to vary in size, from approximately 2.2 to 3.7 kb, although the carA and carB genes themselves did not vary in size in isolates with functional CPS enzyme. A similar large, variably sized intervening sequence was also found between the carA and carB genes of 12 isolates of N. meningitidis and 18 commensal Neisseria isolates comprising nine species. This unexpected organization of the CPS genes in N. gonorrhoeae is therefore widespread throughout the genus Neisseria. PMID- 7773413 TI - Mutations in the glycerol kinase gene restore the ability of a ptsGHI mutant of Bacillus subtilis to grow on glycerol. AB - Although glycerol is not taken up via the phosphotransferase system (PTS) in Bacillus subtilis, some mutations that affect the general components of the PTS impair the ability of cells to grow on glycerol. Five revertants of a pts deletion mutant that grow on glycerol were analysed. They were shown to carry mutations in the glycerol kinase gene. These are missense mutations located in parts of the glpK gene that could encode regions important for the activity of glycerol kinase. The results strongly suggest that the main effect of the PTS on glycerol utilization in B. subtilis is mediated via glycerol kinase. PMID- 7773414 TI - The Bacillus subtilis dnaI gene is part of the dnaB operon. AB - The dnaI gene of Bacillus subtilis, previously identified through the isolation of the dnaI2 mutant, was found to be the second gene of the dnaB operon. The nucleotide substitution in the dnaI2 mutant gene was determined. PMID- 7773415 TI - Evolution of the korA-oriV segment of promiscuous IncP plasmids. AB - Plasmids belonging to Escherichia coli incompatibility group P are of particular interest because they can transfer between, and be stably maintained in, almost all Gram-negative bacterial species. The segment of the IncP alpha plasmid genome between the key regulatory gene korA and the vegetative replication origin, oriV, encodes a series of operons co-regulated with replication and transfer functions by the KorA protein. To determine which of these genes are likely to have an important role in IncP plasmid survival the equivalent region of the distantly related IncP beta plasmid R751 was sequenced. Sequence comparisons show that the kla operon (formerly the kilA locus, which is also responsible for a cryptic tellurite-resistance determinant) is completely absent from R751. Similarly in the kle region, which encodes genes associated with the KilE+ phenotype of unknown function, kleC and kleD, which we proposed arose by a duplication of kleA and kleB, are also completely absent. The genes that are conserved are klcA (formerly kilC, responsible for the KilC+, and recently proposed to be involved in overcoming restriction barriers during transfer), klcB (an ORF interrupted by Tn1 insertion in RK2), korC (a transcriptional repressor which controls the klcK and kle operons), and kleA, kleB, kleE and kleF. A striking feature of the organization in R751 is the lack of the strong transcriptional termination signals which are present in IncP alpha plasmids. The degree of divergence between the plasmids facilitates the identification of motifs of probable functional importance in the primary protein sequences. PMID- 7773416 TI - An operon encoding aspartokinase and purine phosphoribosyltransferase in Thermus flavus. AB - The nucleotide sequence of a 1.1 kb XhoI-HindIII fragment downstream of the malate dehydrogenase (mdh) gene of Thermus flavus revealed the presence of an ORF and an incomplete ORF lacking its NH2-terminal portion, in the opposite orientation to that of the mdh gene. These two genes overlapped with each other, sharing two base pairs, suggesting that these genes are co-transcribed in a single mRNA. One ORF (termed gpt) encoded a protein of 154 amino acids showing significant amino acid sequence similarity to purine phosphoribosyltransferases, such as xanthine-guanine phosphoribosyltransferase of Escherichia coli and human hypoxanthine phosphoribosyltransferase. Cloning and sequencing of the upstream region of the gpt gene, together with sequence comparison of the gene product encoded by the region upstream of gpt, suggested that the upstream ORF encoded two in-frame overlapping aspartokinase genes, askA, encoding the alpha-subunit of 405 amino acids, and askB, encoding the beta-subunit of 161 amino acids, which was part of the 3' portion of askA. Consistent with the sequence data, the askAB and the gpt genes conferred the heat-stable enzyme activities of aspartokinase and phosphoribosyltransferase, respectively, on E. coli. Preliminary characterization of these enzymes produced in E. coli is described. PMID- 7773417 TI - The immunogenicity of recombinant Mycobacterium smegmatis bearing BCG genes. AB - Specific pathogen-free C57BL/6 mice infected with recombinant Mycobacterium smegmatis (rM. smegmatis) bearing BCG genes showed increased splenic survival compared to those receiving the vector control (plasmid DNA only). The mouse passaged rM. smegmatis (J3R) survived in peritoneal macrophages better than the vector control, regardless of whether the macrophages were infected in vivo or in vitro. When rM. smegmatis J3R was cultured in synthetic Proskauer-Beck-Tween medium, protein bands characteristic of BCG culture filtrates and not present in the vector control preparation were observed. Mice immunized with two doses of heat-killed J3R suspended in Freund's adjuvant were able to limit the growth of virulent Mycobacterium tuberculosis within the lung and spleen compared to that observed in control mice receiving adjuvanted vector control or Freund's adjuvant alone. PMID- 7773418 TI - pilO, a gene required for glycosylation of Pseudomonas aeruginosa 1244 pilin. AB - Nucleotide sequencing of a region downstream from the Pseudomonas aeruginosa 1244 pilin structural gene, pilA, revealed an ORF potentially able to code for a protein of M(r) 50,862. This ORF, called pilO, was flanked by a tRNAthr gene, which was followed by a transcriptional termination sequence. The tRNAthr gene and the termination sequence were nearly identical to sequences found immediately adjacent to the pilA gene of several P. aeruginosa strains. A 2200 base mRNA strand, which contained both the pilO and pilA transcripts, was produced from this region, while a 650 base transcript containing only pilA was present in a 100-fold excess over the longer transcript. Hyperexpression of the pilA gene in a PilO- strain resulted in normal pilus-specific phage sensitivity and twitching motility. The pilin produced by this strain had a lower apparent M(r) and a more neutral pl compared to that produced by a strain containing a functional pilO gene. This pilin failed to react with a sugar-specific reagent which recognized pilin produced by the strain containing a functional pilO gene. PMID- 7773420 TI - In situ probing of gram-positive bacteria with high DNA G+C content using 23S rRNA-targeted oligonucleotides. PMID- 7773419 TI - Typing of Staphylococcus aureus strains by PCR-amplification of variable-length 16S-23S rDNA spacer regions: characterization of spacer sequences. AB - To develop a rapid and accurate method of typing large numbers of clinical isolates of Staphylococcus aureus, the spacer region C of the rRNA operon [1391 507 (16S-23S)] was enzymically amplified from 322 strains. When the products were separated by denaturing PAGE, 15 variable-length rrn alleles were demonstrated, ranging in size from 906 to 1223 bp. The variable-length HpaII-digested region C [(region E; 1446-196 (16S-23S)] amplification products were cloned into M13mp18RF to sequence separate variable-length alleles. A total of 17 region E inserts were sequenced, aligned and divided into nine alleles by length (938-1174) and sequence properties. The 16S-23S spacer rDNA varied in length (303-551 bp) and in properties; three alleles contained a tRNAIle gene alone, two alleles contained a tRNAIle and a tRNAAla gene, and four alleles lacked tRNA genes. The sequences of two alleles showed less than 1% variation when isolated from two or three S. aureus strains. The 48 penicillin- and methicillin-sensitive strains were divided into 26 ribotypes; in contrast, the 274 methicillin-resistant S. aureus (MRSA) strains were divided into nine ribotypes (A-I) with 97% typing as either ribotype A or B (rrnL was missing in B). The sequence conservation of the rrn operons argues for the use of the 16S-23S spacer region as a stable and direct indicator of the evolutionary divergence of S. aureus strains. PMID- 7773422 TI - Stress, illness, and the physician. PMID- 7773421 TI - Bacillus thuringiensis protoxin: location of toxic border and requirement of non toxin domain for high-level in vivo production of active toxin. PMID- 7773423 TI - Alcohol and injuries. Time for action. PMID- 7773424 TI - Surrogate decision making. Only one piece of the puzzle. PMID- 7773425 TI - Alcohol and injury. A case-crossover study. AB - OBJECTIVE: To determine whether and to what extent alcohol consumption increases the risk of injury. DESIGN: The case-crossover study is a new research design for assessing rare acute events (such as trauma) in relation to intermittent exposures (such as alcohol use) that have transient effects. All interviewed patients serve as their own controls, and the study design compares exposure during a "case" period, such as the 6 hours prior to injury, with exposure during a "control" period, such as the same 6-hour window on the previous day. SETTING: Emergency centers of a university hospital and a private not-for-profit hospital in a small midwestern city. PATIENTS: Three hundred fifty adults who presented with an injury within 48 hours of the event. DATA COLLECTED: Retrospective self report of alcohol use in each of the 28 days and each of the 30 hours prior to injury, demographic variables, drug use prior to injury, patients' attributions regarding causes of their injury, and weather factors. RESULTS: Primary analysis was based on pairs of observations that were discordant for alcohol use in the 6 hours prior to injury and the same 6-hour window on the previous day. The odds ratio for one or more standard drinks vs none was 2.5 (95% confidence interval, 1.2 to 5.4); for four or more drinks vs three or fewer, 5.0 (95% confidence interval, 1.4 to 27). CONCLUSION: Alcohol use in the 6 hours prior to injury is associated with an increased risk of injury. The findings are consistent with a dose-response effect, but with this sample size no threshold of risk was found. PMID- 7773426 TI - Patients with dementia and their caregivers 3 years after diagnosis. A longitudinal study. AB - OBJECTIVES: To document caregivers' perceptions of the deterioration in functional ability of persons with dementia over time, to identify the most problematic behavior for caregivers at two stages of dementing illness, and to compare the perceived informational needs of caregivers at diagnosis and 3 years later. DESIGN: Single cohort. Surveys were mailed at time 1 and respondents were followed up after 3 years (time 2). SETTING: Midwestern hospital dementia assessment clinic with a family physician director. Continuing care was by community physicians. SUBJECTS: Thirty elderly patients with dementia who were evaluated at the dementia clinic. Data were provided by their caregivers. RESULTS: Patients' scores on the Activities of Daily Living section of the questionnaire declined (bathe self, P = .03; transfer from bed or chair, P = .03; and groom self, P = .06). Significant deterioration in behaviors over time was found in incontinence (P = .04). Fewer patients were depressed at time 2 (P = .02). The patient behaviors found most troublesome at time 1 were worrying about memory loss, losing or hiding things, feeling blue, experiencing restlessness, having difficulty calculating, experiencing a lack of interest, and having false ideas. At time 2, the greatest problems were having a short attention span, failing to recognize persons or things, experiencing a lack of interest, experiencing restlessness, repeating himself or herself, forgetting where he or she is, speaking incoherently, and being incontinent. Questions caregivers most wanted answered at time 1 concerned possible treatment, the future course of illness, and the cause of the symptoms. At time 2, the concerns were the future course of illness, possible treatment, and disease inheritance. There was significantly more interest in family agreement about care (P = .004) and the need for legal guardianship (P = .001) at time 2. CONCLUSIONS: Caregivers' perceptions of the most frequent and troublesome behaviors of patients with dementia were documented at different stages of the disease. The importance caregivers attached to their requests for information reflected changing but continuing needs for reassurance about the patient's diagnosis and treatment and for help with the psychosocial consequences of dementia. Physicians must be aware of caregivers' needs at different stages of the disease process and be equipped to help them appropriately. PMID- 7773428 TI - Delay of diagnosis and empiric treatment of angiotensin-converting enzyme inhibitor-induced cough in office practice. AB - OBJECTIVE: To evaluate the length of time taken to diagnose cough due to the use of an angiotensin-converting enzyme (ACE) inhibitor and the frequency of interim diagnoses and treatments given in an office practice. DESIGN: Retrospective case study. SETTING: Two academic group family practice offices. PATIENTS: Seventeen solicited cases of patients with suspected or known ACE inhibitor-induced cough over a 2-year period. MAIN OUTCOME MEASURES: Documentation in the patient chart of the nature and complaint of the cough; the time between initiation of therapy with the drug and complaint of the cough; the time between initiation of therapy with the drug and assessment of ACE inhibitor-induced cough or discontinuation of drug treatment; other diagnoses given to explain the cough; and other treatments given. RESULTS: There was an average of 14.5 weeks between the initiation of ACE inhibitor therapy and the first documentation of the complaint of cough, and an average of 24.0 weeks between the initiation of ACE inhibitor therapy and documentation of the cough side effect. Physicians made several interim diagnoses prior to recognizing cough as a side effect of ACE inhibitor therapy. Physicians prescribed 30 medications and took two chest radiographs on seven patients experiencing ACE inhibitor-induced cough prior to recognition of this side effect. CONCLUSIONS: The investigation found a significant delay in making the final diagnosis of ACE inhibitor-induced cough. Frequently, physicians gave other diagnoses, ordered unnecessary diagnostic tests, and ordered treatments other than the discontinuation of ACE inhibitor therapy. Earlier identification would be more cost-effective. PMID- 7773427 TI - Surrogates' predictions of seriously ill patients' resuscitation preferences. AB - BACKGROUND: Seriously or terminally ill patients are frequently incapacitated and unable to express their preferences regarding cardiopulmonary resuscitation (CPR). In this situation, family members or other surrogate decision makers are often asked whether they believe the patient would want to be resuscitated. We evaluated the concordance of patient CPR preferences and surrogate perceptions of the patient preferences in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), a large, multicenter study of seriously ill hospitalized patients. METHODS: We compared patient preferences and surrogate perceptions in 1226 pairings in which both patient and surrogate responded to CPR decision questions. We also examined factors that might influence patient-surrogate concordance. RESULTS: Twenty-nine percent of patients with paired data did not want to be resuscitated; 26% of surrogates did not believe the patient they represented would want to be resuscitated. Within pairs, the overall exact agreement with respect to CPR decisions was 74%. For patients favoring CPR, only 16% of the surrogates misconstrued the patient's wishes. For patients who did not want to be resuscitated, however, 50% of the surrogates did not reflect the patient's wishes. If patients reported telling surrogates their CPR preference, concordance was significantly improved if the surrogate believed the patient did not want to be resuscitated and was significantly worsened if the surrogate believed the patient wanted CPR. This finding is likely an artifact of patients being more likely to report their preference to surrogates if that preference was not to be resuscitated. CONCLUSIONS: Surrogates' perceptions of patient CPR preferences are often inaccurate, particularly for those patients who do not want to be resuscitated. Methods to improve communication between patients and surrogates on CPR preferences should be developed and evaluated. PMID- 7773429 TI - Factors associated with having eye examinations in persons with diabetes. AB - OBJECTIVES: To estimate compliance with guidelines on ocular examinations for diabetic persons, to examine factors that affect compliance, and to determine reasons for noncompliance. DESIGN: Cross-sectional population study. SETTING: Primary care setting. PATIENTS: The population is 765 diabetic persons with younger onset and 533 with older onset who participated in the 1990 to 1992 follow-up examination of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. MEASUREMENTS: A medical history was taken in which subjects were asked about eye examinations by ophthalmologists and optometrists. RESULTS: Sixty four percent of the younger-onset group and 62% of the older-onset group had had a dilated eye examination in the previous year. Persons in both groups were more likely to have had a dilated examination if they had a longer duration of diabetes, more severe retinopathy, a history of glaucoma or cataract, and health insurance that covered eye examinations. Persons with younger-onset diabetes were more likely to have had an examination if they were older, were visually impaired, and had more education or higher income. Persons in the older-onset group were more likely to have had an examination if they were female or taking insulin. In those not having an eye examination, 79% and 71% of the younger- and older-onset groups, respectively, reported not having had one because they had no problems with their eyes, and 31% and 35% reported not having been told they needed one. Thirty-two percent and 11% said they were too busy, and 30% and 12% said they could not afford an examination. CONCLUSIONS: Diabetic persons should be educated as to the need for eye care; the results show that barriers to eye care exist in the form of affordability and lack of time. PMID- 7773430 TI - Relationship between the family APGAR and behavioral problems in children. AB - OBJECTIVES: To assess the use of the Family APGAR instrument as a supplement to usual clinical methods for the detection of psychosocial problems in children and to evaluate the relationship between the Family APGAR and physician diagnosis and elevated Child Behavior Checklist (CBCL) scores. DESIGN: Cross-sectional. SETTING: Ambulatory care center of a community-based, university-affiliated family medicine training program. SUBJECTS: One hundred fifty-two parents of children aged 3 to 16 years. MAIN OUTCOME MEASURES: Family functioning was considered poor if Family APGAR scores were 5 or less. For the CBCL, sum total T scores greater than the 90th percentile for nonreferred children were considered clinically significant. Physicians used a checklist to indicate the presence of psychosocial problems or family dysfunction. RESULTS: Agreement between the Family APGAR scores and the physician's detection of child psychosocial problems was weak (kappa = 0.23). There was no relationship between the Family APGAR scores and physician perception of family dysfunction (kappa = -0.05). Although agreement between the Family APGAR and CBCL classifications was weak (kappa = 0.20), families with low Family APGAR scores were more than twice as likely to have children with clinically significant CBCL scores than those with higher scores (risk ratio = 2.08; 95% confidence interval = 1.02 to 4.24). CONCLUSIONS: The relationships among the Family APGAR and CBCL scores and physician detection of child psychosocial problems were weak. Child psychosocial problems were more than twice as likely to be present when the Family APGAR score was low. These findings suggest that family functioning is related to child psychosocial problems, but that the Family APGAR may not improve screening for child psychosocial problems. PMID- 7773431 TI - Tuberculosis in the homeless. AB - The prevalence of tuberculosis in the homeless is on the rise. The presence of human immunodeficiency virus and multidrug-resistant tuberculosis in the homeless has contributed to this high prevalence. Several factors, including alcoholism, substance abuse, and psychiatric illness, combine to make it difficult to diagnose and treat tuberculosis in the homeless. Medical providers are likely to encounter homeless individuals in a number of settings, including emergency departments, community and free clinics, public hospitals, and health maintenance organizations. Appropriate screening, prevention, and treatment should be undertaken in collaboration with local health departments. The use of directly observed therapy and of the treatment regimens published by the Centers for Disease Control and Prevention improves treatment outcomes among the homeless. PMID- 7773432 TI - Interrater agreement in the interpretation of microscopic urinalysis. AB - To determine the reliability of specimen interpretation by outpatient laboratories, 150 consecutive specimens from three family practice centers were analyzed by either two laboratory technicians (n = 99) or two family physicians (n = 51). The results showed good to excellent agreement for contamination (defined as five or more epithelial cells per high-power field) or significant pyuria (five or more white blood cells per high-power field) or hematuria (five or more red blood cells per high-power field). Agreement between laboratory technicians did not differ significantly from agreement between physicians for the interpretation of contamination or pyuria, but for hematuria, agreement was higher between technicians (P = .02). These results suggest that outpatient interpretation of microscopic urine specimens shows levels of interrater agreement similar to or better than other tests that have been evaluated. PMID- 7773433 TI - Adherence to very-low-fat diet by a group of cardiac rehabilitation patients in the rural southeastern United States. AB - This 28-week observational study measured adherence to and acceptability of the diet and nutrition component of an Ornish-type program among patients in a rural southern setting. Ten volunteers followed a very-low-fat (10% of energy), total vegetarian diet and participated in a program of exercise, stress management, and group support. Patients made significant dietary changes and found the diet "acceptable." Three patients consumed less than 10% of energy from fat and two additional patients consumed less than 20% of energy from fat. Eighty-five percent of the patients' meals adhered to a near vegetarian diet. Weight loss ranged from 0.1 to 11.7 kg (0.25 to 26 lb). Lipid values were unchanged. At 12 months, without the benefit of the structured program, one patient reported 100%, six reported 85%, and two reported 50% adherence to the dietary principles. We conclude that motivated patients with coronary artery disease can follow a very low-fat, near vegetarian diet but experience difficulty without a structured program. PMID- 7773434 TI - Uptake of acetylcholinesterase by neurons in the substantia nigra. AB - It is known that acetylcholinesterase is secreted by the dopaminergic neurons of the substantia nigra and has a subsequent action independent of cholinergic transmission. Although non-cholinergic actions of this protein have been demonstrated, the subsequent fate of acetylcholinesterase is unknown. One possibility is that acetylcholinesterase is taken up following secretion into the extracellular space. This hypothesis has been tested in vivo, in both conscious and anaesthetized guinea-pigs. Exogenous acetylcholinesterase (2-20 pM) was infused via a push-pull cannula implanted into either the substantia nigra or the surrounding extranigral regions: the amount subsequently recovered in the perfusate was then compared with control values. Only when the push-pull cannulae were implanted in the substantia nigra was there a marked decrease in the amount of acetylcholinesterase recovered; this selective retention was abolished when the perfusion medium was cooled to 4 degrees C or when the experiment was performed post mortem. Direct visualization of immunocytochemically identified nigral dopaminergic cells revealed co-localized deposits of labelled, exogenous acetylcholinesterase. Moreover, when exogenous acetylcholinesterase was boiled to prevent detection by the assay system and to eliminate any classical enzymatic action, an enhancement in perfusate levels of endogenous acetylcholinesterase was observed from nigral but not from extranigral sites, indicating that endogenous and exogenous acetylcholinesterases were in competition. These results suggest that, within the substantia nigra, secreted acetylcholinesterase may be subject to a temperature- and energy-dependent uptake mechanism. PMID- 7773435 TI - The effects of dopamine on the subthreshold electrophysiological responses of rat prefrontal cortex neurons in vitro. AB - The rat prefrontal cortex is densely innervated by dopaminergic fibres originating in the mesencephalic ventral tegmental area, and dopamine application in vivo has an inhibitory effect. We have studied the effects of dopamine on the persistent sodium current that is present in prefrontal cortex neurons and on the subthreshold electrophysiological responses generated by that current: a slow depolarization and a fast oscillatory activity. Experiments were made in coronal slices of rat frontal cortex (300-400 microns thickness) and intracellular recordings from regularly spiking cells were obtained with 3 M potassium acetate filled glass microelectrodes (80-150 M omega). Dopamine was applied dissolved in the extracellular medium and, in current-clamp recordings, reversibly inhibited the slow subthreshold depolarization. Dopamine was ineffective when applied after tetrodotoxin (1 microM) had blocked the action potentials. This inhibition was dose-dependent in the range of 0.1-10 microM). Dopamine, applied at 10 microM, decreased the steady-state firing frequency and also inhibited the subthreshold fast oscillatory activity. The currents activated in the subthreshold range were recorded with the single-electrode voltage-clamp technique and a clear persistent, tetrodotoxin-sensitive component was isolated. This component was inhibited by 50% in a reversible way by 20 microM dopamine. These results show that dopamine increases the threshold for spike firing and suggest a mechanism for the inhibitory action of this neurotransmitter in the prefrontal cortex. PMID- 7773437 TI - A minimal CGRP gene promoter is inducible by nerve growth factor in adult rat dorsal root ganglion neurons but not in PC12 phaeochromocytoma cells. AB - The calcitonin/CGRP gene is transcribed in thyroid C cells and some neuronal cells but not in other cell types. Although the promoter sequences mediating gene activity in thyroid C cells have been extensively studied, the elements responsible for promoter activity in neuronal cells and its stimulation by nerve growth factor (NGF) have not previously been defined. We report the first use of the calcium phosphate procedure to successfully transfect adult rat dorsal root ganglion neurons, which naturally express the calcitonin/calcitonin gene-related peptide (CGRP) in an NGF-inducible manner. This method was used to characterize the elements in the calcitonin/CGRP promoter which are responsible for its basal activity and NGF inducibility in DRG neurons and in PC12 cells, a neuronally derived cell line which does not naturally express the calcitonin/CGRP gene. Although the sequences required for basal activity are similar in each cell type, we show that a minimal calcitonin/CGRP promoter is NGF-responsive in dorsal root ganglion cells, but that upstream sequences are required for such inducibility in PC12 cells. PMID- 7773436 TI - Block of c-Fos and JunB expression by antisense oligonucleotides inhibits light induced phase shifts of the mammalian circadian clock. AB - Light-induced phase shifts of circadian rhythmic locomotor activity are associated with the expression of c-Jun, JunB, c-Fos and FosB transcription factors in the rat suprachiasmatic nucleus, as shown in the present study. In order to explore the importance of c-Fos and JunB, the predominantly expressed AP 1 proteins for the phase-shifting effects of light, we blocked the expression of c-Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 microliters of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed against c-fos and junB mRNA. A light pulse (300 lux for 1 h) at circadian time 15 induced a significant phase shift (by 125 +/- 15 min) of the circadian locomotor activity rhythm, whereas application of ASO 6 h before the light pulse completely prevented this phase shift. Application of control nonsense oligodeoxynucleotides had no effect. ASO strongly reduced the light-induced expression of c-Fos and JunB proteins. In contrast, light pulses with or without the control nonsense oligodeoxynucleotides evoked strong nuclear c-Fos and JunB immunoreactivity in the rat suprachiasmatic nucleus. These results demonstrate for the first time that inducible transcription factors such as c-Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light-induced phase shifts of the circadian pacemaker. PMID- 7773438 TI - The effects of early postnatal modification of body shape on the somatosensory visual organization in mouse superior colliculus. AB - Different regions of the body of an animal have their own shape and location within visual space. Accordingly, in the superior colliculus there are somatosensory-visual bimodal neurons receiving tactile and visual input from the same region of space. In newborn mice, we changed the position of some body parts within visual space in order to see what happened to the alignment of the somatosensory and visual receptive fields of superior colliculus bimodal neurons. To do this, we modified the shape of the head by displacing the superior vibrissae and the ears, normally in the superior portion of visual space, into the inferior visual space. Analogously, we bent the inferior vibrissae into the superior visual space. At the sixth postnatal week we recorded from somatosensory visual bimodal neurons of the deep layers of the superior colliculus and found that the tactile and visual receptive fields were aligned. Neurons receiving tactile input from the downward-displaced superior vibrissae and ears showed visual receptive fields in the inferior portion of visual space, whereas neurons receiving input from the upward-displaced inferior vibrissae showed visual receptive fields in the superior visual space. These results show that an experience-dependent interaction between visual and somatosensory inputs occurs during development, and that early exposure to abnormal visual-somatosensory experience modifies the organization of multisensory neurons in the superior colliculus. PMID- 7773439 TI - Postnatal development of GABA neurons in the rat somatosensory barrel cortex: a quantitative study. AB - As an estimate of the numerical importance of GABA-containing neurons during development, their quantitative distribution was analysed in the primary somatosensory cortex of rats between postnatal days (P) 5 and 60, using the dissector method and GABA postembedding immunocytochemistry. In relation to the overall number of neurons in the barrel field cortex, the proportion of GABA neurons showed an early significant decrease between P5 and P10 from 14 to 11%, most likely due to termination of transient expression of GABA by some cells. It then remained stable until P20, after which it started slowly but steadily to increase, reaching 14% of the total at P60. The absolute number of GABA neurons also increased by nearly 50% during that period, whereas the number of all neurons remained constant. These changes are seemingly due to a subpopulation of neurons, shown to be of small size, which express GABA late in development. Thus, anatomical adjustments of the cortical GABA system may be observed at least until the end of the second postnatal month, reflecting both delayed maturation and adaptation of this inhibitory circuitry. We suggest the existence of three subpopulations of cortical GABA neurons depending on the time of onset and the regulation of their GABA expression: (i) neurons which express GABA before completion of migration and thus provide for its neurotrophic influence, (ii) neurons which express GABA immediately after completion of migration and build up the cortical inhibitory circuitry, and (iii) neurons which express GABA later in development and represent a substrate of experience-dependent plasticity. PMID- 7773440 TI - The classification and properties of nociceptive afferent units from the skin of the anaesthetized pig. AB - The afferent properties of nerve fibres innervating the hairy skin of the pig hind limb were investigated by recording from 142 single units from the saphenous nerve. Identified single units were isolated using maximal electrical stimulation of the nerve trunk. Afferent units were classified on the basis of their responses to a range of stimuli, both thermal (heating to 60 degrees C and cooling to 10 degrees C) and mechanical (air jet, von Frey type filaments with forces of 0.1-250 mN, and strong pressure with a blunt needle). A-fibre units (conduction velocity 6.3-64 m/s, n = 60) fell into categories that have been described in hairy skin in other mammalian species. Most were mechanoreceptors, although seven typical A-fibre mechanical nociceptors with large, multipoint fields were also isolated. No cutaneous receptive field could be found for 15% of A-fibre units. Out of 62 C-fibre units (conduction velocity 0.49-2 m/s) 40% had no cutaneous field for pressure, heat or cold. Of the C-fibre units with cutaneous fields, 42% were polymodal nociceptors, 38% were mechanoreceptors with a variety of properties, including some excited by noxious heat, and 19% were heat-only nociceptors. C-polymodal nociceptors had large receptive fields up to 12.5 mm across and did not sensitize following strong heating. Twenty units conducted at 2-6.3 m/s, between the main C- and A-fibre bands, and were varied in their responses. Some had properties identical to C-fibre mechanoreceptors whilst four were sensitive cold thermoreceptors and one was a polymodal nociceptor. Two units were mechanical nociceptors with small receptive fields.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773441 TI - Temporal coding of amplitude and frequency modulation in the rat auditory cortex. AB - The rat primary auditory cortex was explored for neuronal responses to pure tones and sinusoidally amplitude-modulated (SAM) and frequency-modulated (SFM) stimuli. Units showed phase-locked responses to SAM stimulation (55%) and SFM stimulation (80%), with modulation frequencies up to 18 Hz. Tuning characteristics to the modulation frequency were mainly band-pass with best modulation frequencies (BMFs) between 4 and 15 Hz. Units with synchronized activity to SFM stimulation showed three response types with respect to the direction of the frequency modulation: 52% were selective to the upward direction, 30% to the downward direction, and 18% had no preference. Triangular frequency modulations were used to test if units were tuned to specific modulation frequencies or to specific rates of frequency change. In the vast majority of units tested the response characteristics were strongly influenced by varying the modulation frequency, whereas varying the rate of frequency change had little effect in the stimulus range used. Units that showed phase-locked responses to SAM and SFM stimulation had similar activity patterns in response to both types of stimuli. BMFs for SAM and SFM stimulation were significantly correlated. Intrinsic oscillations of up to 20 Hz could be seen in the spontaneous activity and after the stimuli independent of the stimulus type. Oscillation frequencies were significantly correlated with the BMFs of the respective units. The results are discussed in terms of a mechanism for periodicity detection based on a temporal code. This could be important for the recognition of complex acoustic signals. PMID- 7773442 TI - Homotypic and heterotypic coupling mediated by gap junctions during glial cell differentiation in vitro. AB - Intercellular communication mediated by gap junctions was investigated during oligodendrocyte differentiation in primary and secondary cell cultures from newborn and adult rats. Two types of communication were considered: ionic coupling and dye-coupling between similar oligodendrocytes selected at the same stage of differentiation (homotypic) and dye-coupling between oligodendrocytes and astrocytes (heterotypic). Intercellular diffusion of fluorescent probes and double whole-cell recordings were used to test the incidence of dye and ionic communication respectively. Progenitor cells, identified with A2B5 antibodies, were characterized by the absence of ionic and dye-coupling, whereas oligodendrocytes, identified with galactosylceramide antibodies, exhibited both types of communication. This homotypic coupling was inhibited by various uncoupling agents, but unaffected by treatments which increased the intracellular concentration of cAMP. In cocultures of astrocytes and oligodendrocytes, Lucifer yellow and sulphorhodamine B were exchanged in both directions. This heterotypic dye-coupling, which could be blocked by octanol, first appeared after 3 weeks in culture and increased to an incidence of 25% after 6 weeks, a developmental pattern comparable to homotypic dye-coupling between oligodendrocytes. In contrast, during the same period, progenitors and microglia were never observed to be dye-coupled with astrocytes. PMID- 7773443 TI - Properties of the hyperpolarization-activated cation current Ih in rat midbrain dopaminergic neurons. AB - Intracellular electrophysiological recordings in current- and voltage-clamp mode were obtained from dopaminergic neurons of the rat mesencephalon in an in vitro slice preparation. In current-clamp mode, a time-dependent anomalous rectification (TDR) of the membrane was observed in response to hyperpolarizing current pulses. In single-electrode voltage-clamp mode, a slowly developing inward current (Ih) underlying the TDR was studied by hyperpolarizing voltage commands from a holding potential of -50 to -60 mV. Ih started to be activated at approximately -69 mV, was fully activated at -129 to -141 mV, with half-maximal activation at -87 mV, and showed no inactivation with time. The time course of development of Ih followed a single exponential, and its time constant was voltage-dependent. At -81 mV, Ih activated with a time constant of 379 +/- 47.6 ms, whereas at -129 mV Ih activated with a time constant of 65 +/- 2.2 ms. Its estimated reversal potential was -35 +/- 4 mV. Raising the extracellular concentration of K+ from 2.5 to 6.5 and to 12.5 mM increased the amplitude of Ih while reducing the extracellular concentration of Na+ from 153.2 to 27.2 mM caused a reduction in amplitude of Ih. Bath application of caesium (1-5 mM) reversibly reduced or blocked the TDR/Ih. Perfusion of tetrodotoxin (0.5-1 microM), tetraethylammonium (10-20 mM) or barium (0.3-2 mM) did not significantly affect Ih. Ih was also present in cells impaled with CsCl-filled electrodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773444 TI - Nerve-dependent plasticity of the Golgi complex in skeletal muscle fibres: compartmentalization within the subneural sarcoplasm. AB - Several recent reports have highlighted the plasticity of the Golgi apparatus during myogenesis, yet the organization of this specialized organelle in innervated skeletal muscle fibres remains poorly understood. Using four bona fide anti-Golgi antibodies, directed against a 210 kDa protein, a 160 kDa sialoglycoprotein, the small GTP-binding protein rab6p, and TGN38, the localization of which covers the various compartments of the Golgi complex, we show by immunofluorescence microscopy that the Golgi complex undergoes considerable reorganization in the course of myogenic differentiation and motor endplate formation in the rat. Unlike the typical perinuclear distribution of the Golgi stacks associated with every nucleus in myotubes, a striking subneural compartmentalization is observed in adult innervated myofibres. In short-term denervated adult muscle fibres, we noticed the presence of the perinuclear Golgi apparatus in extrajunctional regions, a pattern reminiscent of that of developing myotubes. At variance with anti-Golgi antibodies, antibodies to the rough endoplasmic reticulum label structures dispersed throughout the entire sarcoplasm, hence suggesting that it is not the entire membrane/secretory protein synthesis machinery which is compartmentalized, but only the Golgi apparatus. Also, an unexpected lack of immunoreactivity with the TGN38 and alpha-mannosidase II antibodies points to biochemical differentiation of the subneural Golgi apparatus at the adult motor endplate. These new data extend our previous observations on the compartmentalization of the Golgi apparatus in the postsynaptic sarcoplasm of chick muscle fibres, and further illustrate the plasticity of the Golgi apparatus in muscle cells. The specialization of the Golgi apparatus within the subneural compartment provides this particular region with a compartmentalized secretory pathway, and these observations highlight the notion that the level of differentiation of this domain is not only maintained via transcriptional regulation but also by post-translational control mechanisms. PMID- 7773445 TI - Expression of the highly polysialylated neural cell adhesion molecule during postnatal myelination and following chemically induced demyelination of the adult mouse spinal cord. AB - We have investigated the expression of the highly polysialylated neural cell adhesion molecule in the mouse spinal cord during postnatal myelination and in the adult after chemically induced demyelination. By double immunohistochemistry, using a monoclonal antibody (anti-Men B) which specifically recognizes polysialic acid (PSA) units on neural cell adhesion molecule (N-CAM), and an anti-myelin basic protein, a caudorostral gradient of expression of PSA-NCAM was observed at postnatal day 1 (P1), which was inversely related to the gradient of myelination. At P7, PSA-NCAM labelling decreased relative to P1. In white matter, this decrease was correlated with the progression of myelination. PSA-NCAM immunoreactivity persisted in as yet unmyelinated structures, i.e. the corticospinal tract, the dorsomedial part of the ventral funiculus and the lateral funiculi, and decreased with the onset of myelination of these structures at P15. In the adult, PSA-NCAM expression remained in discrete structures, i.e. laminae I and II of the dorsal horn and lamina X around the central canal. The ependymal cells and the astrocyte endfeet under the meninges were also labelled. In addition, PSA-NCAM expression was reinduced on various cells and structures after lysolecithin-induced demyelination of the adult mouse spinal cord. At early times after demyelination, PSA-NCAM was expressed on glial cells around the lesion but also at a distance from this zone. Seven days after injection, cellular PSA-NCAM expression was found around but also within the lesion. This expression was totally abolished 15 days after injection. Double immunohistochemistry for PSA and cell-specific markers showed that the cells which expressed PSA-NCAM after demyelination were oligodendrocyte precursors, reactive astrocytes and Schwann cells. PSA-NCAM re-expression on all cell types was transient and ceased when myelin repair was accomplished. The spatial and temporal regulation of PSA-NCAM expression during development and after demyelination suggests a role for PSA-NCAM in glial plasticity during the myelination and remyelination processes. PMID- 7773446 TI - Receptor expression in olfactory neurons during rat development: in situ hybridization studies. AB - In situ hybridization approaches have been employed to explore the onset and time course of odorant receptor expression during the prenatal development of rats. The critical phase for the maturation of the olfactory system from embryonic day (E) 12 to E18 was analysed. The onset of expression of four receptor genes (OR5, OR14, OR37 and OR124) was found between day E12 and E14. In the early phase of development (E14) a distinct receptor subtype was expressed only in a few hundred neurons; the number increased about two-' to three-fold within a 2 day interval. From the very beginning, spatial segregation of receptor subtypes in distinct expression zones was observed. PMID- 7773447 TI - Increased beta-amyloid precursor protein expression in astrocytes in the gerbil hippocampus following ischaemia: association with proliferation of astrocytes. AB - Increases in beta-amyloid precursor proteins (APP), which include the beta amyloid senile plaque protein present in patients with Alzheimer's disease, have been shown to occur in models of neuronal damage and neurotoxic cell injury. This observation led us to examine the expression of these proteins after transient ischaemic episodes in the gerbil. Animals were killed 2-28 days after ischaemia and APP were detected by immunocytochemistry at the light and electron microscopic levels with an antibody raised against the C-terminal region of these proteins. The gliotic reaction was also examined using glial fibrillary acid protein (GFAP) immunoreactivity. Two days after ischaemia, neuronal cell death was observed in the hippocampal CA1 region accompanied by astrocyte hypertrophy. These hypertrophic astrocytes were found to be GFAP positive but stained weakly for APP. Seven days after ischaemia both astrocyte hypertrophia and hyperplasia, with identified mitotic figures, were observed. These hyperplasic astrocytes were intensely stained by the APP antibody, and were observed up to 28 days after ischaemia. This shows that neuronal cell death produced by transient ischaemia is followed by an increased APP expression which appears to be associated with the hyperplasic astrocytes but not with the initial hypertrophy of this cell population. These results, when taken together with those obtained in other models of neuronal damage or death, clearly suggest that APP expression follows neuronal death and is associated with astrocyte proliferation. PMID- 7773448 TI - Basic fibroblast growth factor opens calcium-permeable channels in quail mesencephalic neural crest neurons. AB - In order to investigate the action of basic fibroblast growth factor (bFGF) in the nervous system, we have studied the ionic signals elicited by this peptide in cultured quail mesencephalic neural crest neurons using patch-clamp and cytofluorimetric techniques. In this preparation stimulation with bFGF induced, with a delay of some tens of seconds, an inward cationic current. Single-channel experiments provided evidence for the activation of a calcium-permeable channel. In single-cell cytofluorimetric measurements, a sustained rise in [Ca2+]i was observed, which was dependent on the presence of external calcium. These events may play a role in the developmental effects of bFGF. PMID- 7773449 TI - Management of ductal carcinoma in situ. AB - Ductal carcinoma in situ (DCIS) is an early, localized stage of breast carcinoma that has an excellent prognosis when it is properly treated. The significant increase in the frequency of diagnosis of DCIS in recent years is the result of both better recognition of DCIS among pathologists and widespread use of screening mammography. Multicentricity, bilaterality and histologic subtype are important considerations in the management of this disease. The clinical presentation of DCIS is the presence of either a palpable mass or a mammographic abnormality, most frequently in the form of an area of microcalcifications. For several decades, total mastectomy was considered the appropriate treatment for DCIS, and it should still be considered the standard to which more conservative forms of treatment must be compared. Breast conservation surgery has been used with increasing frequency in the treatment of DCIS but the adequacy of this approach remains subject to controversy. Segmental mastectomy alone may be applied with caution in carefully selected patients, while the rest of the patients undergoing breast conservation surgery should be treated with breast irradiation. Axillary node dissection is generally considered unnecessary in the treatment of DCIS. There is no role for adjuvant chemotherapy in the management of this disease. The role of tamoxifen in the treatment of DCIS is not clearly defined and it should be given only to patients enrolled in clinical trials. Ongoing research should clarify the controversies surrounding DCIS and enable us to define the optimal management for this disease. PMID- 7773450 TI - Thick cutaneous melanoma of the trunk and extremities: an institutional review. AB - The objective of this study was to review our experience with thick cutaneous melanoma of the trunk and extremities and to identify subgroups of long-term survivors. Ninety-one patients admitted between the years 1977 and 1987, with cutaneous melanoma of the trunk or extremities, Breslow thickness > or = 4.0 mm, or a Clark's level V lesion form the basis of this review. Node positive clinical stage II patients had a 5-year survival rate of 32%. Five-year survival for node positive clinical stage III patients was 0% (P < 0.0001). Node negative clinical stage II patients, and those found to be histologically node positive, had no survival difference, P = 0.88. Sixty per cent of node negative patients with an extremity primary survived 5 years, while patients with a node positive truncal primary had a survival of 14%, P = 0.005. In conclusion, most patients present with local-regional disease. Patients with node negative extremity lesions have the best chance for cure. PMID- 7773451 TI - Prognostic value of ploidy of primary tumour and nodal secondaries in colorectal cancers. AB - Tumour ploidy is of prognostic value in colorectal cancer, DNA aneuploid tumours having a worse outlook. Nearly all studies have concentrated on the DNA content of the primary tumour. We have examined the ploidy of the primary tumour and its lymph node metastases in 71 cases of Dukes' stage C disease, to see whether this provides greater prognostic information than the primary alone. Analysis was performed using formalin-fixed, paraffin-embedded tumour sections. Ploidy of primary and metastases was different in 20 cases (28%), aneuploid nodes being seen with diploid primaries and vice versa. Ploidy of both the primary (chi 2 = 4.86, P = 0.03) and secondary (chi 2 = 4.86, P = 0.03) tumours predicted survival in univariate analysis. Combining the ploidy of primary and nodes, three prognostic groups could be defined--diploid primaries with diploid metastases (hazard relative to both aneuploid, 0.36) had significantly better survival than cases where the ploidy of the primary and nodes were mixed (relative hazard 0.47 0.56), which did better than cases with aneuploid primary and nodes. This study demonstrates that ploidy variation between primary and secondary tumours is common, and better prognostic information may be gained by studying both. PMID- 7773452 TI - Changes in serum sex steroid levels during megestrol acetate therapy. AB - We hypothesized that megestrol acetate (MA) may work on breast carcinoma by inducing changes in serum sex steroid levels. We prospectively measured levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) in 18 postmenopausal women before and during megestrol acetate therapy. MA significantly suppressed serum FSH, LH, DHEA and E1 levels. However, this was accompanied by a marked increase in serum E2 levels as measured by radioimmunoassay performed on whole serum. MA did not cross-react with the anti E2 antibodies used in the assay. Elevated E2 levels also occurred in oophorectomized and/or adrenalectomized patients indicating the ovary and adrenal are not the source of the elevated E2 levels. We conclude that MA may be metabolized to oestrogenic compounds that crossreact with antibodies to E2, explaining the elevated E2 levels observed. The effects of these oestrogenic metabolites on breast carcinoma are unknown. PMID- 7773453 TI - Carbon dioxide volume and intra-abdominal pressure determination before the creation of a pneumoperitoneum. AB - Laparoscopic surgery generally is regarded as a safe procedure when a preset pressure is used in the carbon dioxide insufflator. However, a fixed pressure setting is not appropriate when insufflating a very large or a very small abdomen. Presently, extrapolation from the commonly used 15 mm Hg to an appropriate and safe pressure cannot be easily determined except by a crude trial and error method. We developed an anthropometric formula to calculate the total abdominal cavity capacity and the corresponding pressure necessary to obtain safe pneumoperitoneum. This anthropometric formula calculates the total abdominal capacity by measuring one diameter from the symphysis pubis to the xyphoid bone, a second diameter as half the initial measurement, and a third diameter by dividing the waist measurement (minus an estimated percentage of body fat) and dividing that product by pi. The product of the three diameters is then multiplied by a constant (K = 0.5). We studied prospectively 20 patients whose indications for laparoscopic surgery necessitated creation of a pneumoperitoneum. The patients were divided into two groups: group A (n = 10), patients who were observed with the intra-abdominal pressure fixed at 15 mm Hg while recording the amount of distension produced in the abdominal cavity during creation of the pneumoperitoneum; and group B (n = 10) in whom pneumoperitoneum was obtained based on the initial volume of carbon dioxide-insufflation previously calculated using our formula. Based on our observations, we conclude that this anthropometric formula can be used successfully in predicting a safe level of insufflation in relation to the patient's size. PMID- 7773454 TI - Safe laparoscopic surgery: tubal ligation without prior pneumoperitoneum. AB - Twelve years of experience with tubal ligation by the laparoscopic route at two highly specialized centers of female sterilization are discussed; special attention is given to the technique and results achieved. The number of intraoperative and postoperative complications was very low compared with data reported elsewhere. This article attempts to present the knowledge gained by using the laparoscopic technique, at a time when the use of laparoscopic surgery is extending around the world. The direct insertion of trocars without prior pneumoperitoneum has proved to be safe, and the risks of intraabdominal (visceral or vascular) injuries are minimized by observing simple rules, such as clamping of the relaxed abdominal anterior wall with towel clips, maintaining sharpened trocars, and using the extended index finger as a limit to introduce only the tip of the trocars. We consider a medical history of previous laparotomy secondary to peritonitis and open abdominal treatment absolute contraindications for this technique. PMID- 7773456 TI - Endoscopic retrograde cholangiopancreatography and endobiliary stenting in the treatment of biliary injury resulting from liver trauma. AB - Two patients with the bile duct injury secondary to blunt liver trauma are presented. Endoscopic retrograde cholangiopancreatography (ERCP) proved to be a useful diagnostic and therapeutic modality in the treatment of these patients. This report advocates the use of ERCP and endobiliary stenting in the management of biliary injury resulting from liver trauma. PMID- 7773455 TI - Laparoscopic Nissen fundoplication--a curative, safe, and cost-effective procedure for complicated gastroesophageal reflux disease. AB - We prospectively evaluated the cases of 52 patients who underwent laparoscopic Nissen fundoplication from October 1992 to January 1994 for patient outcome, satisfaction, hospital stay, hospital cost, and disability. All cases were evaluated with historical findings, routine chemistry studies, upper gastrointestinal series, fluoroesophagography for esophageal motor function, gallbladder ultrasonography, and esophagogastroduodenoscopy. Six patients required esophageal manometry for diagnosis. All patients had refractory esophageal reflux disease or complications of chronic esophageal reflux. Forty nine (94%) of the 52 cases were completed laparoscopically. Ninety percent of those were cured of their symptoms and returned to a normal life-style. The percent had significant improvement, with rare episodes of reflux or dysphagia, and received antacids only occasionally. Hospital stay was reduced to 2.3 days, compared to 8.3 days for the open technique. Hospital cost was reduced to $6,870, compared to $11,990 for the open technique. Mean time until return to work was 15 days in the laparoscopic group, compared to 42 days in the open Nissen group. There were two major complications (4%) and 12 minor complications (24%). There were no deaths. Fifty-one of 52 patients stated that they would recommend the procedure for others with the same problem. Laparoscopic Nissen fundoplication is a safe and effective treatment for refractory esophageal reflux and its complications and has the extra benefit of reduced hospital cost and stay and a more rapid return to work. Preoperative esophageal manometry and 24-h esophageal pH testing may be used selectively with excellent results. PMID- 7773457 TI - Feasibility of laparoscopic cholecystectomy for patients with a nonvisualized gallbladder on drip infusion cholangiography. AB - We report here the operative findings, the incidence of successful laparoscopic treatment, and the perioperative complications in patients with nonvisualized gallbladder on drip infusion cholangiography (DIC). Eighty-five patients with a nonvisualized gallbladder on DIC were entered into the study. None of the patients had a minimal adhesive gallbladder; 51 to 85 patients (60.0%) had moderate adhesive gallbladders, and 34 (40.0%) had severely adhesive ones. The rate of successful laparoscopic treatment, including laparoscopy-assisted abdominal surgery, was 97.6% (83 of 85 patients). Perioperative complications occurred in only three patients (3.5%), and there were no deaths related to the operation. Thus, when patients with a nonvisualized gallbladder on DIC undergo laparoscopic cholecystectomy, meticulous procedures must be carried out; however, as the rate of successful laparoscopic treatment is high, cholecystectomy under laparoscopy is feasible for experienced surgeons. PMID- 7773458 TI - Diagnostic laparoscopy in women with acute abdominal pain. AB - Nineteen women with acute lower abdominal pain of uncertain etiology underwent diagnostic laparoscopy during a 2-year period from August 1991 to August 1993 and were retrospectively reviewed. All patients, aged 12 to 44 years, were premenopausal. Laparoscopy provided definitive diagnosis in all 19 patients. Laparoscopic findings included appendicitis (11 cases), pelvic inflammatory disease (five cases), significant ovarian cysts (two cases), and ectopic pregnancy (one case). Successful laparoscopic procedures included appendectomy (five cases), and salpingo-oophorectomy (one case). Five patients required only diagnostic laparoscopy. Eight patients required conversion to an open procedure because of anatomical considerations (six cases) or equipment failure (two cases). Median operative time was 71 min, and median postoperative hospital stay was 2 days. Most diagnostic procedures were performed on the same day as admission, resulting in a median hospital stay of 3 days. Diagnostic laparoscopy performed in premenopausal female patients with acute lower abdominal pain of unknown etiology provides diagnostic accuracy as well as therapeutic capabilities and prevents unnecessary laparotomy. PMID- 7773459 TI - Laparoscopic restoration of intestinal continuity after Hartmann procedure. AB - Two cases of laparoscopic restoration of intestinal continuity are presented. The procedures were technically straightforward and both patients did well. These cases add to a small but growing literature documenting the technical feasibility of laparoscopic intestinal surgery. The potential risks and benefits of this minimally invasive technique are discussed. PMID- 7773460 TI - Laparoscopic partial splenic resection. AB - Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach. PMID- 7773461 TI - Laparoscopy-assisted colonoscopic polypectomy. AB - One of the most feared complications in the removal of moderate-sized or large sessile polyps is colonic perforation. Complete colonoscopic total excision of these kinds of polyps can be safely undertaken using laparoscopic assistance, which enables prompt diagnosis and treatment of perforation. Laparoscopy-assisted endoscopic polyp excision can be safely performed, avoiding critical septic complications and can also help in the selection of patients to appropriate colonic resection without increasing morbidity or mortality. PMID- 7773462 TI - Steam sterilization of laparoscopic instruments. AB - Because of the intricate internal parts of laparoscopic instruments, questions have been raised about the efficacy of cleaning and sterilization techniques. To assess these risks, hamburger meat was inoculated with high concentrations of vegetative pathogens and packed into laparoscopic cannulas. All openings of the cannulas were sealed during steam sterilization cycles ranging from 3 to 10 min in different experiments; cultures were obtained after cooling. Experiments were then performed using heat-resistant spore forms. Our studies showed that both the standard 10-min cycle and the 3-min "flash" were uniformly successful in killing all pathogenic microorganisms. A 7-min steam sterilization was necessary to kill spores within sealed cannulas. We conclude that a standard 10-min cycle within the steam autoclave provides complete sterilization of laparoscopic instruments; the 3-min "flash" sterilization is appropriate and safe for instruments that have been inadvertently contaminated or dropped during a surgical procedure. PMID- 7773463 TI - Videothoracoscopic resection of a posterior mediastinal tumor. AB - We report a complete videothoracoscopic resection of a posterior mediastinal tumor (neurilemmoma) in a 43-year-old man. The tumor was located in the right cupula of pleura and well demarcated. The tumor was mobilized under videothoracoscopic guidance and extracted from the thoracic cavity through a trocar site. The postoperative course was uneventful, and the postoperative pain could be reduced. PMID- 7773464 TI - Laparoscopic manipulation of a malfunctioning peritoneal dialysis catheter in a child. AB - A case of outflow obstruction of a peritoneal dialysis catheter in a 12-year-old boy is presented. The cause of obstruction was identified and remedied by laparoscopic means. Laparoscopy has important diagnostic and therapeutic roles in the evaluation of malfunctioning peritoneal dialysis catheters. PMID- 7773465 TI - Laparoscopic cholecystectomy in a 23-month-old infant. AB - We describe a laparoscopic cholecystectomy performed on a 23-month-old girl. The experience and the data in the literature indicate that this approach offers particular advantages for treatment of pediatric patients without increasing the operative risk. PMID- 7773467 TI - Exacerbation of groin hernias after laparoscopy. AB - The incidence of pneumoperitoneum-related complications of laparoscopy is quite low. The more common complications are due to improper placement of the needle during insufflation and those related to the cardiorespiratory system. We describe two cases who underwent prolonged laparoscopic surgery and presented postoperatively with hernia. PMID- 7773466 TI - Management of an abdominal cerebrospinal fluid pseudocyst using laparoscopic techniques. AB - Abdominal cerebrospinal fluid (CSF) pseudocysts are reported to occur in < 1% of ventriculoperitoneal shunts. Management options include various types of shunt revisions with or without aspiration or excision of the pseudocyst. We report a case in which laparoscopy was utilized in a 12-year-old boy to excise a portion of the pseudocyst, remove the shunt catheter tip from the residual pseudocyst, and reposition it in the peritoneal cavity. The patient experienced no complications from the procedure, and there has been no recurrence of the pseudocyst after 12 months of follow-up observation. This case report demonstrates a novel approach to the management of CSF pseudocysts that is minimally invasive, allows direct drainage of the pseudocyst, and permits manipulation and optimal repositioning of the shunt catheter. PMID- 7773468 TI - Benign cystic mesothelioma in a male patient: surgical treatment by the laparoscopic route. AB - We report a case of a benign cystic mesothelioma in a 44-year-old man. The patient was asymptomatic, and the cystic formation was discovered by chance in the course of ultrasonography for urological disorders. Benign cystic mesothelioma is a rare pathology, and only 19 cases have been described in male patients. The differential diagnosis versus other cystic diseases can only be defined histologically and is of critical importance to clinical management. Surgery is mandatory for both diagnosis and treatment. In the case reported here, a minimally invasive laparoscopic approach allowed not only histological diagnosis of benign cystic mesothelioma, but also its surgical treatment by the same route. PMID- 7773470 TI - Making loops in laparoscopic surgery: state of the art. PMID- 7773469 TI - Laparoscopic simple cystectomy in a man. AB - Laparoscopic surgery is rapidly being assimilated into the urologic armamentarium. Already many operations commonly done by an open approach are being performed laparoscopically. We report on the laparoscopic performance of a simple cystectomy in a spinal cord-injured male patient suffering from recurrent pyocystis. The procedure proved to be technically feasible, with the patient experiencing a short convalescence period. PMID- 7773471 TI - A technique for needle insufflation in obese patients. PMID- 7773472 TI - Transperitoneal laparoscopic approach to lumbar discectomy. AB - Recognition of the benefits derived from laparoscopic cholecystectomy led to the evaluation of a laparoscopic approach to the lumbar disc space. Goals included minimizing postoperative pain and disability while still achieving adequate access to the disc space, including adequate discectomy under direct visualization. Described herein are the methods used to develop the laparoscopic exposure necessary to allow anterior resection of the lumbar disc, as well as preliminary results of the first 15 patients to undergo laparoscopic discectomy. PMID- 7773473 TI - A comparative retrospective study of thoracoscopy versus thoracotomy for the treatment of spontaneous pneumothorax. AB - Thoracoscopic surgery has been claimed to reduce patient disability, recovery time, and hospital costs compared with open surgery. We analyzed 25 patients who had undergone thoracoscopic surgery and compared the outcome to 24 patients who had undergone conventional surgery for spontaneous pneumothorax. The thoracoscopic group was able to return to work and daily activities earlier and had less impairment of shoulder movement. There was a loss of sensation corresponding to the dermatomes where the thoracoscopic ports were placed, which could have resulted from compression of the intercostal nerves by the instruments. However, a similar loss of sensation was found in the thoracotomy group. We conclude that thoracoscopy may be the method of choice for the treatment of spontaneous pneumothorax, although further methodological development should be done. PMID- 7773474 TI - Videoendoscopic procedures in thoracic surgery: technical aspects and report of removal of a mediastinal cyst. AB - Current videoendoscopic technology and percutaneous techniques of exposure and dissection have been successfully applied to abdominal surgery with favorable results. Application of this technology to our practice of thoracic surgery is the basis of this report. Video-assisted thoracic surgery was performed in 36 patients for the following indications: Raynaud's syndrome, undefined pulmonary nodule, persisting spontaneous pneumothorax, T1 bronchial carcinoma, and mediastinal cyst. Videoendoscopic surgical procedures were accomplished using double-lumen endotracheal anaesthesia and a percutaneous stapling device. Procedures performed using this technique include thoracic sympathectomy, wedge or keel excision, blebectomy, lung apex stapling, parietal pleurectomy, and dissection of the mediastinal cyst. Median operating time was 45 min (range, 15 to 90 min). Tissue diagnosis was obtained in all patients. Median diameter of excised nodules was 10 mm (range, 7 to 70 mm). There were no operative deaths. The single complication was a prolonged air leak. This new method of thoracic surgery appears to benefit the patients. For us it proved a secure way to perform thoracic surgery. Our case of removal of a benign cyst in the posterior mediastinum shows that video-assisted thoracic surgery has expanding applications in the field of general thoracic surgery. PMID- 7773475 TI - Routine prophylactic vena cava filter insertion in severely injured trauma patients decreases the incidence of pulmonary embolism. AB - BACKGROUND: Trauma patients are at increased risk for venous thromboembolism despite routine prophylaxis. A five-year retrospective review of pulmonary embolism at the Medical Center Hospital of Vermont showed that four types of injuries (head injuries, spinal cord injuries, complex pelvic fractures, and hip fractures) accounted for 92 percent of pulmonary emboli in patients on the trauma service. STUDY DESIGN: Beginning July 1991, all patients who met criteria for a high-risk injury (excluding hip fractures) had prophylactic vena cava filters inserted percutaneously in the radiology suite. Weekly impedance plethysmography was performed for the detection of deep vein thrombosis. Following discharge, abdominal duplex ultrasound was performed at one month, six months, and yearly to check filter position and patency. RESULTS: To date, a total of 63 patients, or 2 percent of the total trauma population, had prophylactic vena cava filters inserted. There were 19 (30 percent) deep vein thromboses in this population of patients and one patient had a pulmonary embolism (1.5 percent). Overall there was significant (chi-square, p < 0.00072) reduction of pulmonary embolism on the trauma service compared to the historical controls. Follow-up examination with abdominal duplex ultrasound showed a 30-day patency rate of 100 percent and a one and two-year patency rate of 96.1 +/- 3.8 percent by life-table analysis. CONCLUSIONS: We concluded that prophylactic vena cava filters are efficacious in decreasing the risk of pulmonary embolism in high-risk trauma patients. PMID- 7773476 TI - Isoperistaltic jejunal interposition for intractable postgastrectomy alkaline reflux gastritis. AB - BACKGROUND: The Roux-en-Y gastrojejunostomy is a popular method in the operative treatment of alkaline reflux gastritis and other postgastrectomy sequelae, but is associated with a high incidence of the so-called "Roux stasis syndrome." The Henley jejunal interposition has been used occasionally, albeit not widely, as an alternative to the Roux-en-Y reconstruction. STUDY DESIGN: Six patients underwent Henley gastrojejunoduodenostomy to treat severe (Visick grade IV) symptoms following Billroth I and II procedures for peptic ulcer disease. All interposed jejunal segments were 40 cm in length and isoperistaltic in orientation. All patients had follow-up examination and telephone interview (mean 4.3 years, range 2.2 to 7.8 years). RESULTS: All patients noted dramatic improvement after remedial surgery in the first year of follow-up. After the first postoperative year, all patients remained virtually symptom-free (Visick grade I and II) with no complaints of gastrojejunal stasis or bile acid reflux. CONCLUSIONS: This experience suggests that the Henley jejunal interposition is our effective method of treating reflux gastritis and is not associated with the poor emptying frequently associated with the Roux-en-Y reconstruction. PMID- 7773477 TI - Highly selective vagotomy plus Jaboulay: a possible alternative in patients with benign stenosis secondary to duodenal ulceration. AB - BACKGROUND: The treatment of patients with duodenal ulcers has undergone radical changes in recent years. Symptomatic stenotic obstruction of the gastric outlet, however, has remained a specific indication for elective operation, with gastric resection (Billroth I or II) and vagotomy often used as options for intervention. STUDY DESIGN: The present report describes the results of highly selective vagotomy (HSV) in combination with lateral Jaboulay gastroduodenostomy in the treatment of patients with benign stenosis secondary to duodenal ulceration. Functionality of results and patient satisfaction have been focal aspects in our assessment. RESULTS: During a period of five years, HSV plus Jaboulay was performed upon 19 patients (14 men and five women, with an average age of 55 years). No operative mortality was seen. The postoperative follow-up period ranged from 12 to 60 months. There were no ulcer recurrences, the functional results (roentgenographic double-contrast technique) were excellent, and patient satisfaction was high (Visick grade I, 67 percent; Visick grade II, 33 percent). CONCLUSIONS: As evidenced by the results, HSV plus Jaboulay seems to represent a convincing alternative to gastric resection in the treatment of patients with benign stenosis secondary to duodenal ulceration. PMID- 7773479 TI - Twenty-four hour monitoring of pH in the gastric tube replacing the resected esophagus. AB - BACKGROUND: Peptic ulcers in the gastric tube replacing the resected esophagus develop silently and cause serious problems. In this study, the acidity of the gastric tube was examined by 24-hour pH monitoring to determine if the acidity of the gastric tube was sufficient to cause peptic ulcers. STUDY DESIGN: The acidity of a gastric tube was evaluated by 24-hour pH monitoring of both the fundus and the antrum in 55 patients treated for carcinoma of the esophagus. The correlation between the fasting serum gastrin concentration and the intraluminal acidity of the completely vagotomized gastric tube was examined. RESULTS: In the patients with high postoperative acidity in the fundus or the antrum (46 percent of the 41 patients examined), the intraluminal pH remained consistently low, even long after operative treatment. Significant correlations existed between the percentage of time that the pH remained below 3 preoperatively and postoperatively in both the fundus and the antrum (r = 0.4777, p = 0.0386, and r = 0.7597, p = 0.0002, respectively). The percentage did not decrease significantly postoperatively. A significantly negative correlation (r = 0.783401, p < 0.0001) was found between the fasting serum gastrin level and the proportion of time that the nocturnal pH in the antrum remained below 3. CONCLUSIONS: Even long after esophagectomy, the pH of the gastric tube is low enough to cause peptic ulcers, especially in patients with high preoperative acidity. In these patients, the intraluminal pH in the antrum of the gastric tube correlates inversely with the fasting serum gastrin level. PMID- 7773478 TI - Wound breaking strength and healing after suturing noninjured tissues. AB - BACKGROUND: Many operative procedures involve suturing healthy, previously nontraumatized tissues. The present study was done to investigate the wound breaking strength and healing after suturing noninjured tissues. STUDY DESIGN: A new experimental model of muscluloaponeurotic suture in the mouse is described and used to investigate the scar breaking strength, the concentration of 5 hydroxyproline, the extrusion of suture material, and the histological characteristics of the repair process. Scar quality was compared at three weeks between a group of mice in which suture was done without prior tissue injury (n = 24) and three groups of mice (n = 24 each) with prior tissue injury (tight ischemic suture, incision, and cautery). Silk (n = 8), polyglactin 910 (n = 8), and polypropylene (n = 8) sutures were used within each group. RESULTS: Scars resulting from the suturing of healthy tissues had less breaking strength than those with ischemic, incised, or cauterized wound edges (507 g compared to 590, 730, and 732 g, respectively; p < 0.001) and had a lower 5-hydroxyproline concentration (5.1 ng/mg compared to 6.09, 6.77, and 7.49 ng/mg, respectively; p < 0.01). Polypropylene sutured scars had a higher breaking strength than silk (690 compared to 608 g, p < 0.01) or polyglactin 910 (690 compared to 626 g, p < 0.01). Most of the stitches were extruded from the scar independent of the suture material. CONCLUSIONS: The quality of a scar does not seem to be as good when wound edges are healthy than when they have been previously injured. PMID- 7773480 TI - Evaluation of necrotizing pancreatitis in the opossum by dynamic contrast enhanced computed tomography: correlation between radiographic and morphologic changes. AB - BACKGROUND: The ability to quantitate the extent of acinar cell necrosis with contrast-enhanced computed tomography (CT) during acute pancreatitis is uncertain. STUDY DESIGN: Acute hemorrhagic necrotizing pancreatitis was induced in opossums by obstructing their biliopancreatic duct for up to seven days or by retrograde injection of a bile-trypsin taurocholate mixture into the opossum pancreatic duct. At selected times, groups of three animals each were examined by dynamic contrast-enhanced CT, and the abnormalities on the images were quantitated. Immediately following CT, the animals were sacrificed and the extent of necrosis was quantitated by morphometric analysis of tissue samples at the light microscope level. RESULTS: The CT severity score as well as the degree of nonenhancement on dynamic contrast-enhanced CT were both closely correlated with the extent of acinar cell necrosis (r = 0.91 and r = 0.97, respectively). CONCLUSIONS: The degree of pancreatic nonenhancement on dynamic contrast-enhanced CT can be used to quantitate the extent of pancreatic necrosis during acute necrotizing pancreatitis. PMID- 7773481 TI - Influence of local treatment on the recurrence rate of ductal carcinoma in situ. AB - BACKGROUND: Screening mammography has resulted in a significant increase in the diagnosis of ductal carcinoma in situ (DCIS). The role of breast conservation therapy and the long-term recurrence rate are still controversial. This article compares mastectomy, wide excision alone, and wide excision with radiation as treatments for DCIS. STUDY DESIGN: One hundred twenty-four cases of DCIS were retrospectively reviewed and were found to be pure DCIS by a senior pathologist. The mean age at diagnosis was 60 years (range, 33 to 81). Originally, 101 patients (81 percent) presented with calcification on mammogram, and 23 (19 percent) presented with a palpable mass. Histologic data showed that 54 (44 percent) had noncomedo type lesions, 46 (37 percent) had comedo type, and 24 (19 percent) had unknown type DCIS. RESULTS: Four of the 124 patients had a recurrence during a mean follow-up period of 43 months. Recurrence is defined as any development of DCIS or invasive carcinoma in the ipsilateral breast. There was one (1.3 percent) recurrence in the 75 patients treated with mastectomy (an adenocarcinoma of the chest wall), which occurred at 59 months. Treatment was 5,750 cGy to the chest wall and the patient is free of disease 37 months postradiation. There were three (11 percent) recurrences at 14, 21, and 29 months, respectively, in the 28 patients treated with wide excision alone. All three recurrences were found by calcifications on mammogram and all patients had comedo type original lesions. Two recurrences were pure DCIS of the breast. Both patients were treated with mastectomy and are free of disease at 33 and five months, respectively. The third recurrence was an invasive colloid carcinoma of the breast. Treatment was a modified radical mastectomy; the patient is free of disease after 62 months. There were no recurrences in the 21 patients who were treated with wide excision and radiation. Average total dose of radiation was 5,835 cGy (range, 4,500 to 6,480). CONCLUSIONS: The results of this study indicate that both mastectomy and wide excision with radiation are associated with very low recurrence rates. Wide excision alone is associated with a higher recurrence rate. However, all recurrences were detected mammographically and all lesions were salvaged by mastectomy. Therefore, the ultimate local control and survival rates were similar for all three modalities. PMID- 7773482 TI - Understanding surgical knot security: a proposal to standardize the literature. AB - BACKGROUND: There is very little published data concerning the knot handling properties of suture materials. The few studies that are available on this subject contain discrepancies in nomenclature, testing methods, and in the type of data reported. To date, there has been no effort to present what is currently known concerning knot security in a unified format. STUDY DESIGN: A review of the literature was conducted to determine what is currently known concerning surgical knots, the efficiency of these knots, testing techniques, and nomenclature. The structures of common surgical knots were analyzed and their relationships determined. The results of the various studies were analyzed and a summary of existing data was prepared. RESULTS: Based on current literature and a thorough analysis of surgical knots, a standard method for testing knot efficiency and a standard nomenclature were proposed. Suture security has been shown to be strongly influenced by the type of knot used. Knots in which the second throw contains two turns are most efficient. CONCLUSIONS: Existing studies have demonstrated a strong variation in the efficiency of different surgical knots. Standards for testing and nomenclature have been presented. Effort now needs to be directed in three areas: simulating in vivo conditions, testing knots under these conditions, and determining the factors that make some suture materials more efficient in knot holding than others. PMID- 7773483 TI - Predicting axillary node positivity in patients with invasive carcinoma of the breast by using a combination of T category and palpability. AB - BACKGROUND: In spite of the development of numerous new tumor markers, axillary lymph node status continues to be the single most important prognostic variable regarding survival of patients with carcinoma of the breast. This study was undertaken to determine whether or not the combination of T category (TNM staging system) and palpability would be a better predictor of nodal positivity than T category alone. STUDY DESIGN: Clinical and pathologic data were analyzed for 1,554 patients who underwent axillary lymph node dissection as part of their treatment for invasive carcinoma of the breast. Data were analyzed by the primary lesion's T category and whether or not the lesion was palpable. RESULTS: Five hundred fifty-one (35 percent) of 1,554 axillary node dissections contained metastases. The probability of nodal involvement was significantly higher and the average tumor diameter was slightly, but significantly, larger for palpable T1b, T1c, and T2 lesions when compared with nonpalpable lesions within the same T category (all p values less than or equal to 0.003). The probability of lymphatic tumor emboli or vascular invasion was generally higher for palpable lesions compared with nonpalpable lesions and increased as lesions got larger. The percentage of patients with low nuclear grade and favorable histology was generally lower for patients with palpable lesions compared with those having nonpalpable lesions and decreased as lesions got larger. CONCLUSIONS: Nodal positivity was significantly higher for palpable T1b, T1c, and T2 carcinoma of the breast when compared with nonpalpable carcinoma of the breast within the same T category. The combination of T category and palpability was a more accurate predictor of nodal positivity than T category alone. PMID- 7773484 TI - Survival impact of lymph node metastasis in TNM stage III carcinoma of the colon and rectum. AB - BACKGROUND: Node-positive (TNM stage III) adenocarcinoma of the colon and rectum consists of tumors with a widely variable prognosis. To predict the outcome of patients with stage III carcinoma, we assessed the survival impact of the number and level of lymph node metastasis and other clinicopathological variables. STUDY DESIGN: A retrospective study was performed on 538 patients with stage III carcinoma of the colon and rectum who underwent curative resection at Chang Gung Memorial Hospital between 1980 and 1989. Ten or more lymph nodes in each resected specimen were identified microscopically. Multivariate analysis was used to determine the independent variables. RESULTS: The relative survival rates at five and ten years were 52 and 42 percent, respectively. Tumor morphology, depth or tumor penetration, histologic grade, and the status (number and level) of nodal involvement were significant in the univariate analyses. Only grade and nodal status remained significant in the multivariate analysis. Based on the nodal status, these patients were separated into three groups: stage IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more nodes or presence of pN3). The five-year survival rates for patients with stages IIIA, IIIB, and IIIC disease were 69, 44, and 29 percent, respectively. Compared with patients with stage IIIA disease, the odds of death for patients with stages IIIB and IIIC carcinoma were 2.1 (95 percent confidence interval: 1.5 to 2.8, p = 0.0001) and 3.3 (95 percent confidence interval 2.4 to 4.5, p = 0.001), respectively. CONCLUSIONS: We suggest that stage III adenocarcinoma of the colon and rectum be divided into three substages: IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more positive nodes or presence of pN3. PMID- 7773485 TI - Prostaglandin E1 attenuation of ischemic renal reperfusion injury in the rat. AB - BACKGROUND: Prostaglandin E1 (PGE1), a vasodilating prostaglandin, has been shown to protect against renal ischemic-reperfusion injury in acute experiments. The purpose of this study was to determine whether or not delayed administration of PGE1 would also be effective, as it has been suggested to be, in ischemic hepatic injury. STUDY DESIGN: In a chronic model, rats underwent 60 minutes of total renal ischemia followed by either NaCl or PGE1 therapy delivered at either time 0, 30, or 60 minutes after reperfusion. Serum creatinine and renal histology were evaluated for seven days. In an isolated perfused kidney model, kidneys were similarly treated but were removed and perfused in order to measure renal vascular resistance (VR). RESULTS: Prostaglandin E1 administration at time 0 resulted in lower creatinine values when compared with controls at both day 2 (2.1 +/- 0.4 compared with 4.2 +/- 0.9 mg/dL) and day 7 (0.9 +/- 0.1 compared with 2.3 +/- 0.8 mg/dL). Conversely, no improvement was observed when PGE1 was delayed for either 30 or 60 minutes. Renal morphology at seven days was essentially intact in PGE1-treated rats (time 0) whereas changes characteristic of acute tubular necrosis were observed in control kidneys. Ischemia caused a twofold increase in VR compared with nonischemic controls (6.18 +/- 1.12 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes of perfusion). Prostaglandin E1 treated kidneys (time 0) had a VR that was unchanged from that calculated for nonischemic controls (3.28 +/- 0.63 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes). CONCLUSIONS: These data demonstrate that after total renal ischemia, PGE1 administration at reperfusion ameliorates the expected injury, whereas delayed treatment is ineffective. Decreased vascular resistance may be responsible for this protective effect. PMID- 7773487 TI - Venous thromboembolism in trauma patients. PMID- 7773486 TI - Levels of portal and systemic blood cytokines after colectomy in patients with carcinoma or Crohn's disease. AB - BACKGROUND: Cytokine overproduction has been observed in different pathophysiologic conditions, including sepsis, carcinoma, inflammatory disease, and tissue injury induced by operation. Colectomy is a procedure that may result in excessive cytokine release through the portal vein. The respective effects of an operative procedure, perioperative septic complications, and of the disease itself on cytokine production are still not known. STUDY DESIGN: This study was done to investigate the variations in the levels of interleukin-1 beta (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) in portal and systemic blood during and after colectomy in patients with malignancy or with Crohn's disease. Blood samples were collected intraoperatively from portal and systemic veins of 24 patients undergoing colectomy for either Crohn's disease (n = 13) or carcinoma (n = 11), and postoperatively (from days 1 to 5) from systemic veins. The changes in blood levels of cytokines and CRP in patients with an uneventful colectomy (n = 19) were compared to changes in patients whose colectomy was complicated by sepsis (n = 5). Similar changes in cytokines and CRP levels were compared between patients with malignancy and those with Crohn's disease. RESULTS: The portal and systemic blood levels of IL-1, IL-6, TNF-alpha, and CRP were significantly correlated before and after colectomy. In portal blood, the level of IL-6 was significantly higher after colectomy than before. In systemic blood, the levels of CRP, TNF alpha, and IL-6 before colectomy were significantly higher in patients with Crohn's disease than in patients with malignancy. After uneventful colectomy, a temporary increase in CRP, TNF-alpha, and IL-6 was noted in systemic blood, followed by a rapid decrease, although systemic blood cytokine levels remained significantly higher after colectomy complicated by sepsis. Interleukin-1 beta levels in both portal and systemic blood remained unchanged during and after colectomy, regardless of the indication for operation and its outcome. CONCLUSIONS: Colectomy causes acute release of cytokines and CRP in both the portal and systemic circulation. The increase in IL-6 observed after colectomy in portal blood and subsequently in systemic blood suggests local production from the resected specimen, or at least from the area of resection. Cytokine production, especially of IL-6, was modified not only by the underlying disease itself, as higher levels were observed in Crohn's disease before colectomy, but also by the presence of perioperative septic complications. PMID- 7773488 TI - Remedial operations for correction of bile reflex joints. PMID- 7773489 TI - Improvement of technique for adult orthotopic liver retransplantation. PMID- 7773490 TI - The paramedian approach to open laparoscopy. PMID- 7773491 TI - Expediting the open diagnostic peritoneal lavage. PMID- 7773492 TI - Distal pancreatectomy using the ultrasonic dissector. PMID- 7773493 TI - Perixiphoid extension of the midline incision. PMID- 7773494 TI - An alternative method to traditional pyloroplasty using a circular stapler. PMID- 7773495 TI - The abdominal compartment syndrome: the physiological and clinical consequences of elevated intra-abdominal pressure. PMID- 7773496 TI - Epidemiology, diagnosis, precautions, and policies of intraoperative anaphylaxis to latex. PMID- 7773497 TI - Cause and prevention of electrosurgical injuries in laparoscopy. PMID- 7773498 TI - Corrective treatment and anatomic considerations for laparoscopic cholecystectomy injuries. PMID- 7773501 TI - Immunohistochemical analysis of bcl-2 and p53 expression in breast carcinomas: their correlation with Ki-67 growth fraction. AB - We examined 59 breast cancers for p53 and bcl-2 protein expression by immunohistochemistry. The results were correlated with Ki-67 immunostaining. p53 negativity was noted in 40 cases and the remaining 19 tumours were p53-positive. Thirty-six tumours showed strong expression of bcl-2 and in 23 no staining for this protein was observed. We found statistically significant reverse correlation between expression of p53 and bcl-2 in majority of carcinomas: 31 cases were bcl 2 positive and p53-negative, and 14 tumours were bcl-2-negative and p53-positive. Six carcinomas showed no nuclear staining for Ki-67 and in the remaining 53 the percent of cancer cells positive for Ki-67 ranged from 1 to 60 (mean: 14.6). In these 53 cases we found that bcl-2-positive tumours were characterized by lower proliferation than bcl-2-negative tumours, the mean value of Ki-67 immunostaining being 10.7% and 23.0%, respectively. p53-negative tumours showed lower proliferation than p53-positive tumours: mean Ki-67 index was 10.2% and 23.9%, respectively. We conclude that immunohistochemically detected p53 and bcl-2 proteins show a significant inverse relationship in majority of breast carcinomas and their expression correlates with tumour proliferation (Ki-67 immunostaining). PMID- 7773500 TI - Detection of microsatellite instability in human colorectal carcinomas using a non-radioactive PCR-based screening technique. AB - The aim of the present study was to establish a rapid, non-radioactive screening method for the detection of microsatellite instability (MIN). MIN is the primary characteristic of the mutator phenotype in tumours constituting hereditary non polyposis colon cancers (HNPCC). We investigated 30 patients suffering from colorectal cancer using a non-radioactive PCR-based technique. MIN was present in 7 of 30 (23%) of the cases. There was a statistically significant correlation between MIN and localization of the tumour. Five of 7 (72%) tumours with MIN but only 4 of 23 (17%) tumours without MIN were localized in the proximal colon (P < 0.01). There was a tendency to higher MIN frequency in tumours of patients with familial clustering of cancers. However, this was statistically not significant (P > 0.05). In addition, no correlation between MIN and tumour grade and stage was found. For the investigations in the present study we used a non-radioactive PCR-based method followed by denaturating polyacrylamide gel electrophoresis and silver staining. This method is highly sensitive and reproducible. Thus, PCR based analysis using a non-radioactive staining technique represents a comprehensive tool for MIN screening in diagnostic pathology. PMID- 7773499 TI - Microsatellite instability: new aspects in the carcinogenesis of colorectal carcinoma. AB - Very recently a new molecular mechanism in the tumorigenesis of colorectal carcinoma has been described which is closely linked to hereditary non-polyposis colonic cancer (HNPCC). Ubiquitous changes in the length of simple repetitive DNA sequences between constitutional and tumour DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal carcinoma. Such microsatellite instabilities have been shown to be the phenotypical marker of mutations in the human homologues of prokaryotic mismatch repair genes (MutS, MutL, MutH). These data provide crucial new tools in the detection of patients at high risk of developing colon cancer and other HNPCC-related carcinomas. In addition, these developments provide new insights into a new, presumably primary event in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate ("mutator phenotype") and thus to cancer. PMID- 7773502 TI - Calcifying solitary bone cyst: morphological aspects and differential diagnosis of sclerotic bone tumours. AB - Fourteen solitary bone cysts (SBC) with large areas of calcification (7 in the femur, 4 in the humerus, and 1 each in the pelvis, the tibia and the scapula) and 402 SBC from the Hamburg Bone Tumour Registry were reviewed in a retrospective study. The analysis was done with emphasis on the clinical, radiological and histological appearances. SBC are well known lesions, but calcifying SBC (CSBC) or extensive extragnathic cement-like bone productions are rare. The clinical and radiological differential diagnosis includes fibrous dysplasia, chondroma, low grade chondrosarcoma and osteosarcoma. Bits of this cement-like matrix are detectable within the wall of approximately 70% (278 of 402) of SBC from the registry. CSBC are changed SBC. The intraoperative confirmation of the diagnosis on a frozen section by the bone pathologist leads to curettage which is currently the most common therapy in this benign lesion. PMID- 7773503 TI - Immunohistochemical localization of cytochrome P450 2E1 in human pulmonary carcinoma and normal bronchial tissue. AB - Cytochrome P450 2E1 (CYP2E1) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2E1 can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2E1 in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients. Seromucous glands showed expression of CYP2E1 in 19 and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the corresponding cases of primary pulmonary carcinoma showed staining for CYP2E1. In 11 of these 13 cases, CYP2E1 was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2E1 between adenocarcinomas and squamous cell carcinomas. No association was observed between the expression of CYP2E1 in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2E1 in seromucous glands and bronchial epithelium (r = 0.61, P < 0.01) of normal tissue. We conclude that CYP2E1 can be present in both normal and neoplastic bronchial tissue. PMID- 7773504 TI - Intracellular localization, vesicular accumulation and kinetics of daunorubicin in sensitive and multidrug-resistant gastric carcinoma EPG85-257 cells. AB - In the human gastric carcinoma cell line EPG85-257P (parent) induction of resistance to daunorubicin (DAU) was achieved by selection with stepwise increased concentrations of the drug. The new variant was named EPG85-257DAU and was shown to overexpress the mdr1 gene product 170 kDa P-glycoprotein (P-Gp) as demonstrated by immunocytochemistry and mdr1-specific RT-PCR. To investigate the intracellular pathway of DAU the subcellular distribution of this autofluorescent drug was studied in the resistant cells and compared to its chemosensitive counterpart EPG85-257P. When sensitive cells were exposed to DAU the drug rapidly accumulated in the nucleus until cell death. No redistribution of DAU to the cytoplasm was observed. In resistant cells exposed to the drug DAU also accumulated in the nucleus but to a lesser extent than in parent cells. Following exposure, nuclear fluorescence was observed to decrease over a time period of up to 48 h. Six hours after DAU exposure formation of fluorescent vesicle formation started in the perinuclear region and increased continuously. After 48 h nuclear fluorescence was no longer detectable and DAU was located exclusively in vesicles. During this period the vesicles moved from the region of origin to the cell periphery. A pulse chase experiment showed, that vesicles may contain DAU derived from the nucleus. Treatment of EPG85-257DAU cells with DAU in conjunction with the chemosensitizer cyclosporin A (CsA) increased nuclear fluorescence without impairing vesicle formation. Disruption of microtubules by nocodazole led to an accumulation of vesicles in the perinuclear region indicating that microtubules are involved in vesicular transport. Treatment of EPG85-257DAU cells with the actin disruptor cytochalasin B led to accumulation of vesicles in the cell periphery indicating that actin may be involved in exocytosis. Uptake and efflux of DAU and rhodamin (RH) were determined in sensitive and resistant cells using a fluorescence activated cell sorter. Uptake of both compounds was distinctly lower in resistant than in sensitive cells. When resistant cells preloaded for 2 h with RH subsequently were incubated in drug free medium the substance was rapidly released indicating transmembrane transport by P-Gp. In contrast, despite expression of P-Gp in resistant cells no considerable release of DAU was observed for up to 2 h under the same experimental protocol. This indicates that in resistant cells intracellular DAU at least in part may be inaccessible for P-Gp and that vesicular drug transport appears to contribute to DAU resistance by removing intracellular DAU via exocytosis. PMID- 7773505 TI - Morphological modifications of apoptosis in HL-60 cells: effects of homocysteine and cytochalasins on apoptosis initiated by 3-deazaadenosine. AB - Using electron microscopy, confocal laser scanning microscopy and measurements of intact DNA we have studied the morphology and DNA degradation of human leukaemia HL-60 cells undergoing drug initiated apoptosis. Apoptosis was initiated by 100 microM 3-deazaadenosine (c3Ado), 25 microM c3Ado plus 1 mM homocysteine thiolactone (Hcy) and 100 microM c3Ado plus 5 micrograms/ml cytochalasin B (CB). Two different phenotypes of apoptotic cells (APC), blebbed and non-blebbed, were present in the cultures. Blebbed APC dominated in cultures exposed to c3Ado, whereas most APC in cultures treated with c3Ado plus Hcy and all the APC in cultures treated with c3Ado plus CB displayed a non-blebbed phenotype. A more pronounced reduction of the chromatin/cytoplasm ratio, lower volume fractions of uncondensed chromatin and higher volume fractions of highly condensed chromatin (micronuclei) were found in cultures exposed to c3Ado and c3Ado plus Hcy when compared with cultures exposed to c3Ado plus CB. A partial inhibition of c3Ado apoptosis by CB was confirmed by measurements of intact DNA. The inhibitory effect of CB was not reproducible by CE, indicating that CB exerts its effect by an actin independent mechanism. Both blebbed and non-blebbed APC displayed nuclear fragmentation, segregation of organelles and cytoplasmic vesiculation, suggesting that the differences between the phenotypes were restricted to the cytoplasmic membrane. We were not able to demonstrate the presence of F-actin by fluorescein isothiocyanate-phalloidin staining in blebbed APC nor in non-blebbed APC in cultures treated with c3Ado plus Hcy. Non-blebbed APC in cultures treated with c3Ado plus CB displayed foci of F-actin at the internal part of the cytoplasmic membrane. This suggests that F-actin is preserved by the mechanism by which CB inhibits blebbing, and may indicate that blebbing of the cytoplasmic membrane during apoptosis is associated with F-actin deficiency rather than a result of actin-myosin interactions. PMID- 7773506 TI - Freeze-fracture immunocytochemistry for intracellular localization of serotonin in mast cells stimulated with compound 48/80. AB - Changes of intracellular localization of serotonin in rat mast cells were examined by freeze-fracture immunocytochemistry, to prevent the translocation of the serotonin antigen. Rat peritoneal cells including mast cells were stimulated in vitro with compound 48/80, at 17 degrees C for 0, 30 or 60 s for exocytosis to occur. The mast cells were fixed, quickly frozen and freeze-fractured to expose the antigen on the fractured surface. They were immunostained with serotonin antibody, and the immunoreactions on the fractured surface were examined on ultrathin sections by electron microscopy. Unstimulated mast cells exhibited serotonin localization mostly in each intragranular matrix. In contrast, mast cells stimulated for 30 s exhibited increased serotonin in their intergranular cytoplasm. Mast cells showed more distinct immunoreactions in the cytoplasm where degranulation would be promoted after 60 s. It is suggested that intracellular release of serotonin occurred in the stimulated mast cells. PMID- 7773507 TI - Mitochondrial abnormalities of muscle tissue in mice with juvenile visceral steatosis associated with systemic carnitine deficiency. AB - A mouse with juvenile visceral steatosis (the JVS mouse) has been recognized as a novel animal model for systemic carnitine deficiency. We examined cardiac, skeletal and smooth muscle cells in JVS and control mice by light and electron microscopy. Cardiac and skeletal muscle cells of these mice at 4 weeks of age exhibited a ragged-red appearance after trichrome staining. Electron microscopy, demonstrated increased numbers of mitochondria and lipid droplets in the cells. Compression or distortion of the myofibril bundles, primarily due to the increased number of mitochondria, suggests the possible existence of a functional disturbance of the cardiac and skeletal muscle. In the urinary bladder, only one or two large lipid droplets and slightly increased number of mitochondria were recognized in the perinuclear region of the smooth muscle cells. At 8 weeks of age, the mouse enzyme histochemistry specific for mitochondria, such as cytochrome c oxidase and succinic dehydrogenase, and oil red O staining, confirmed further increases in the number of mitochondria and lipid droplets in the heart. However, the accumulation of these organelles in the skeletal and smooth muscle cells was no greater than that noted in JVS mice at 4 weeks of age. In the cardiac muscle cells, autolysosomes or autophagic vacuoles containing electron-dense membranous, lamellar or whorled structures closely associated with mitochondria and pseudoinclusion bodies in the nucleus were recognized, and bundles of myofibrils were buried under numerous mitochondria, suggesting the existence of disturbed contractile function in the heart of JVS mice. These results indicate that this murine strain associated with systemic carnitine deficiency exhibits a generalized mitochondrial abnormality in the muscle system especially in the heart. PMID- 7773508 TI - Structural analysis of the formation of glomerular microaneurysms in the Habu venom model. AB - The goal of this study has been to characterize the process of glomerular microaneurysm formation and to separate it from capillary ballooning. In the Habu venom model glomerular capillary ballooning and glomerular microaneurysm formation are seen regularly. The sequence of glomerular lesions leading to a glomerular microaneurysm has been examined and it is clear that the process starts with local mesangiolysis. This may proceed to mesangial expansion and/or ballooning of glomerular capillaries but in contrast to ballooning the formation of a glomerular microaneurysm is based on endothelial defects. The process occurs as follows: once initiated by mesangial failure lesions extend along the mesangial axis. As long as the extension of the lesion encroaches on divergent capillary branches, capillary ballooning by "coalescence" is the result. This process comes to an end when convergent capillary branching is reached and two capillaries join. At this point endothelial disruptions occur, blood and mesangial spaces merge and a glomerular microaneurysm is established. Further growth of the microaneurysm occurs following damage spreading along the lobular axis. The entire process has been reconstructed and is presented in a three dimensional model. PMID- 7773509 TI - Nucleolar segregation as an early marker for DNA damage; an experimental study in rats treated with 4-hydroxyaminoquinoline 1-oxide. AB - Male 6-week-old Sprague Dawley rats were given a single intravenous injection of 4-hydroxyaminoquinoline 1-oxide (4HAQO) at a dose of 20 mg/kg in order to produce ultrastructural changes as possible morphological biomarkers for toxicity. Immunohistochemically demonstrated formation of 4HAQO-DNA adduct was correlated with the changes found. Nucleolar alteration, demonstrable by electron microscopy as segregation of nucleolar components into granular and fibrillar compartments, was evident in cells of the target organs, exocrine pancreas and adrenocortex, but not of the non-target liver parenchyma. Sequential observation clarified that such alteration was highest in frequency 6 h and 4 h after 4HAQO administration in pancreatic acinar cells and adrenocortical cells respectively. Electron microscopically, apoptotic changes of acinar cells were evident 2 h after injection of 4HAQO. DNA adduct formation was consistently demonstrated in the same target organs showing nucleolar segregation, the highest frequency being noted 4 h after 4HAQO treatment in both pancreatic acinar cells and adrenocortical cells. Our results thus indicate an identity of the target cells for nucleolar segregation and 4HAQO-DNA adduct formation which correlates with 4HAQO-toxicity. We suggest that nucleolar segregation occurs subsequent to the generation of DNA damage. PMID- 7773510 TI - Reaction of human lungs to aspirated animal fat (ghee): a clinicopathological study. AB - We report the clinical findings and pathological lung changes in four children following a cultural practice of forced feeding with animal fat (ghee) during infancy. The clinical presentation was of acute or chronic chest infection which failed to respond to antimicrobial therapy. The radiographic features ranged from extensive bronchopneumonia to collapse/consolidation and bronchiectasis. The light microscopy findings included diffuse mononuclear interstitial pneumonia, intraalveolar desquamation of pneumocytes, lipid granuloma formation, lung atelectasis and bronchiectasis. In the two children with longstanding reactions, the striking feature was the minimal lipid engulfment by the macrophages, the continuation of the mononuclear interstitial pneumonia, bronchiectasis and minimal lung fibrosis. In these two older children, the lung lymphatics were probably the main channels for drainage of the aspirated ghee. PMID- 7773511 TI - Participation of T lymphocytes in atherogenesis: sequential and quantitative observation of aortic lesions of rats with diet-induced hypercholesterolaemia using en face double immunostaining. AB - Using en face double immunostaining coupled with electron microscopy, we studied the temporal and spatial distribution of T lymphocytes and macrophages during the development of atherosclerosis in a diet-induced rat model fed an atherogenic diet for 2-40 weeks. T lymphocytes and macrophages adhered to the aortic surface by 2 weeks on the diet, with subsequent migration under the endothelium, and formed a fatty streak-like lesion. Analysis of the cellular components revealed that infiltration of T lymphocytes was most prominent in the incipient phase of lesion formation accounting for 60%, 29% and 34% of mononuclear cells appearing in 2-week lesions of the superior thoracic, inferior thoracic and abdominal segments of the aorta, respectively. After the incipient phase, the relative number of T lymphocytes in the three segments of the aorta showed a slow decline; the proportion of T lymphocytes to macrophages was approximately 1:3 to 1:4 in 10 to 20-week lesions. An overall view of the lesional cells often demonstrated direct cellular contact between T lymphocytes and macrophages. Further, OX6/ED1 double immunostaining demonstrated that Ia antigen was expressed on most macrophages. In later stages, breakdown of foamy macrophages occurred, and the extracellular accumulation of lipids and cell debris became prominent. The results demonstrated that in the diet-induced rat model, together with macrophages, large numbers of T lymphocytes participated in all stages of aortic lesions, initially adhering to the surface at prelesional stages and later as the principal component of the atherosclerotic lesion. It is possible that the method described here will provide a good tool for examining the role of T lymphocytes in atherogenesis. PMID- 7773513 TI - Congress on In Vitro Biology. Denver, Colorado, May 20-24, 1995. Abstracts. PMID- 7773514 TI - Empowerment in health care. PMID- 7773512 TI - Neural cell adhesion molecule immunoreactivity in Merkel cells and Merkel cell tumours. AB - We have analysed the expression of the neural cell adhesion molecule (NCAM) in normal Merkel cells of pig and human skin, and in nine neuroendocrine carcinomas of the skin (Merkel cell carcinomas). NCAM immunoreactivity was observed in virtually all Merkel cells, both in epidermis and vibrissae of pig snout skin and in human epidermis. Immunostaining surrounded the entire surface of Merkel cells and was not restricted to the contact areas between Merkel cells and nerve terminals. All Merkel cell carcinomas studied were also positive for NCAM. The immunostaining pattern of the tumour cells was similar to that observed in normal Merkel cells; the immunoreactivity was confined to the cell membranes. These results suggest that NCAM may be used as an immunohistochemical marker for both Merkel cells and Merkel cell tumours. PMID- 7773515 TI - Collaboration through project management. AB - This paper focuses on project management and examines its value for nurse managers. The paper explores the implementation of project management and its contribution to the collaboration between two Trusts in West Suffolk, UK. It argues that project management could serve the interest of nurse managers within the changing culture of the health service. The collaborative project was funded by the East Anglian Regional Audit Team. PMID- 7773516 TI - Clinical management: a special case*. AB - This paper briefly discusses the development of some of the principles of case management as they have been applied in the community. As a clinical management system we argue that the key elements of case management could and should be applied within institutional settings. We draw as an example Ashworth Special Hospital recently criticized for its lack of co-ordinated care by a Public Inquiry Committee. The resulting discussion focuses upon a rehabilitation framework which could be used to implement case management within such a setting; the implementation of such a framework and the benefits that would be gained. PMID- 7773517 TI - The management of professionals: the preferences of hospital sisters and charge nurses. AB - This analysis of the preferences of how sisters and charge nurses are managed is the result of a two centre descriptive study using theoretical models of professionalism, developing preferences and exercising situational leadership. It was conducted to determine if the management structure preferred by sisters and charge nurses, in a general acute hospital setting, supported the professionalism of nursing. The outcomes were intended to help develop a strategic plan for the future of nursing and the management of nurses. The research instruments were a self-completed questionnaire (19 were returned, a response rate of 31.1%) and four semi-structured interviews. The findings disclosed some dissatisfaction with the present management arrangements. The sisters and charge nurses felt that their priorities for practice and professional issues were better supported by clinically involved, ward-based senior nurses than by unit-based senior nurses with a general management function. However, sisters' and charge nurses' discussions with ward-based senior nurses were apparently less effective than discussions in peer groups which led to influential collegial autonomy. This preferred management style can be supported by the use of situational leadership theory which would enhance collegial autonomy and professional satisfaction. Recognition of the sisters and charge nurses preferences and adjustment of their management would therefore enable them to participate effectively in organizational decision-making. PMID- 7773519 TI - The developing role of the educational facilitator. AB - The National Health Service has undergone significant reforms in recent years. A consequence of these reforms has been to recast the relationship between service providers (Trusts) and educational providers (University Departments). This relationship is increasingly formalized through contractual processes and the ability of University Departments to respond promptly to identified needs within Trusts may become inhibited. As a Trust employee the Educational Facilitator can provide practice-led educational initiatives utilizing the resources found within the clinical environment. Such initiatives would be in accord with Trust objectives and be put into operation with ease. The current role of the educational facilitator is explored with key role components and functional areas identified. The paper concludes with a consideration of the role in the development of professional knowledge and strategies for knowledge development. PMID- 7773518 TI - Audit in the British National Health Service. AB - This paper is about audit as it exists inside the broader framework of quality control within the National Health Service. It will define medical audit briefly and examine its antecedents in exploring why it was introduced. The paper will proceed to analyse the underlying economic and political reasons for the Government's strategy for audit, and assesses its contribution to the debate about quality in health care. The paper concludes by considering the future direction of audit arising out of the recent emphasis placed on multi professional clinical audit. PMID- 7773520 TI - An analysis of case management--the efficient utility of human resources, but to what end? AB - Case management has been credited as a modality to reduce the lengths of hospital admission and to utilize human resources more effectively. The approach concentrates on the process of delivering care to constantly improve the productivity levels of health care practitioners. The United Kingdom government policy is certainly progressing towards cost-containment and cost-effective service delivery. However, it needs to be considered if the culture of nursing would be able to adopt the strategy. Firstly, it needs to be questioned if nurses have the managerial and financial acuity to successfully perform the role. Secondly, the adoption of case management may potentially negate the value of some aspects of professionally skilled nursing care which has little cost-benefit analysis but provides the true essence of nursing. With a further advancement of cost-centered care, case management may become the anti-thesis of an inherently caring profession. PMID- 7773521 TI - Looking back to the future. PMID- 7773522 TI - The health-care elective experience. PMID- 7773523 TI - The effectiveness of nursing: a review. AB - This paper describes the findings of a literature review of the effectiveness of nursing. Three journals were selected in which this type of study was most likely to be published. A diversity of attempts to measure nursing effectiveness with various types of patient was found. Generally, however, there was a lack of rigour in study design and sample sizes were too small to be able to draw conclusions. No studies were found which undertook a cost-effectiveness analysis of nursing interventions. Suggestions for the way forward in measuring nursing effectiveness are given, together with questions to be addressed by nursing research. PMID- 7773525 TI - The development of clinical leadership through supported reflective practice. AB - The notion of clinical leadership is significant in current nursing practice, particularly since recommendations made by the Department of Health in 'The Strategy for Nursing'. However, while it is a concept that many nurses aspire to implement, in reality the operationalizing of such a concept is fraught with difficulty. This paper aims to explore the issue of clinical leadership through a collegiate model developed in a particular practice area. The development of this collegiate relationship is articulated through the mediums of reflective practice and clinical supervision. A model of collegiality is offered as an approach to the integration of the spheres of clinical leadership. If reflective practice is to be a reality then it is essential that both clinical leaders and practitioners engage in such processes within a supportive culture. PMID- 7773524 TI - A critique of 'at risk' pressure sore assessment tools. AB - This paper critiques pressure sore risk assessment tools. No attempt is made to describe individual tools in detail as this literature is available elsewhere. The economic case for risk assessment is presented along with the criteria for an effective risk assessment instrument. Reliability and validity studies are reviewed in relation to three risk assessment tools: Norton, Waterlow and Braden. Finally a number of issues related to threshold scores, research design and the need to view pressure sores as a clinical problem rather than a nursing problem are discussed. PMID- 7773526 TI - Introduction of the use of structured pain assessment for post-operative patients in Kenya: implementing change using a research-based co-operative approach. AB - A research-based project was conducted to introduce structured pain assessment on a surgical ward at a general hospital in Kenya, East Africa. The aim was to improve pain control, and subsequently patients' recovery and satisfaction with care. It was agreed that the ultimate aim was to develop and use a common tool for pain assessment throughout the hospital, thereby reducing disparity in various clinical areas, and raising standards of patient care. The project was seen as a pilot, and planned introduction of the pain assessment took place over 1 month. This paper describes the findings in relation to the patient sample, and perceptions of nurses taking part. It also contains reflections about action research, and how it may enter the scene as a way of understanding the whole picture retrospectively. PMID- 7773527 TI - What neurological patients regard as quality of life. AB - The aim of this study was to investigate how patients with progressive neurological disorders describe what they perceive as quality of life. The patients (n = 169) were interviewed while staying at a neurological rehabilitation centre by way of an open question, what 'quality of life' represented to them. Patients' statements were classified and a comparison was made with Kajandi's three levels of factors constituting quality of life. The categories that came forth were 'living in a sense of affinity', 'being independent', 'living on one's own terms' and 'feeling that life is meaningful'. The statements constituting the basis of the categories were impressive and illustrated wisdom. The results underline the uniqueness of each patient's situation, and how important it is that nursing and treatment are adjusted to the needs of the individual. PMID- 7773528 TI - Listening to the voices of older patients: an existential-phenomenological approach to quality assurance. AB - The motivation behind this study was a desire to gain access to the experiences of elderly people receiving nursing care in hospital. Previous experience with quantitative approaches to quality assurance had led to dissatisfaction with their neglect of the patient perspective or reliance on patient satisfaction questionnaires. An existential-phenomenological approach was used in an attempt to reconstruct patients' experiences as reported in their own words. Themes which emerged from the data and are reported here focus on 'routine geriatric care', 'care deprivation', 'depersonalization', and 'geriatric segregation'. The findings are discussed against the background of literature about nursing care of elderly people. It is suggested that in the setting studied, limitations posed by past management deficiencies, under-staffing and poor physical environment contributed to the situation reported. Trained nurses felt they worked hard to give the best care they could but, with a high ratio of untrained staff and lack of continuing education, they were aware that their levels of achievement were far from ideal. The study demonstrates that, with an appropriate methodology, it is possible to gain access to how patients' experience their care and in this sense the attempt to 'listen to the voices of patients' was successful and gives pointers to developing more patient-sensitive quality-assurance processes. PMID- 7773529 TI - Using research to implement change: the introduction of group activities on a psychiatric unit. AB - Staff in a psychiatric unit of a general hospital proposed the introduction of a programme of structured group activities, based on their casual observation that patients were sometimes unoccupied and bored. It was decided to collect data systematically in order to inform the implementation of activities. An activities record sheet was developed to list all activities taking place over a 1-week period. Questionnaires were administered to patients (n = 23) and staff (n = 20) on the unit to seek their views on the value, type, timing, frequency and location of activities as well as on other related aspects. Overall, staff made practical and realistic suggestions regarding the implementation of structured group activities. The data collected, although useful in planning change, raised questions about the poor quality of patients' responses and the low response rate (50%) from staff. Implications of these and other issues are discussed. PMID- 7773530 TI - Colostomy irrigation--a safe practice? PMID- 7773531 TI - Respiratory effects of baclofen and 3-aminopropylphosphinic acid in guinea-pigs. AB - 1. The effects of the GABAB receptor agonists, baclofen and 3 aminopropylphosphinic acid (3-APPi) given by the subcutaneous or intracerebroventricular (i.c.v.) route were examined on minute ventilation (V), tidal volume (VT) and respiratory rate (f) due to room air and carbon dioxide (CO2)-enriched gas hyperventilation in conscious guinea-pigs. 2. Baclofen (0.3-10 mg kg-1, s.c.) produced a dose-dependent inhibition of V and f due to room air and CO2 inhalation. The maximum inhibition of room air breathing V was 85% +/- 3 and f was 74% +/- 3 at 10 mg kg-1, s.c. The maximum effects on CO2-induced hyperventilation were 68% +/- 9 and 51% +/- 6, for V and f respectively. Only the highest dose of baclofen studied (10 mg kg-1) produced a significant inhibition of VT due to room air breathing (46% +/- 6) and CO2 breathing (38% +/- 11). 3. 3 APPi (0.3-100 mg kg-1, s.c.) did not affect V, VT or f due to room air breathing or CO2 inhalation at any dose tested. Also, i.c.v. administration of 3-APPi (100 micrograms) did not affect ventilatory responses due to room air breathing or CO2 inhalation. 4. Pretreatment with the GABAB antagonist, CGP 35348 3-aminopropyl (diethoxymethyl) phosphinic acid (3-30 mg kg-1, s.c.) blocked the respiratory depressant effects of baclofen (3 mg kg-1, s.c.) in a dose-related fashion. 5. Intracerebroventricular (i.c.v.) administration of CGP 35348 (50 micrograms) blocked the respiratory depressant effects of baclofen. CGP 35348 given alone either i.c.v. or s.c. had no effects on respiration due to room air or CO2 inhalation.6. Pretreatment with either the GABAA antagonist bicuculline (30 mg kg 1, s.c.) or the opioid antagonist, naloxone (1 mg kg-1, s.c.) had no effect on the respiratory depressant action of baclofen(3 mg kg-1, s.c.).7. These results show that baclofen inhibits ventilation due to room air breathing, and attenuates the hyperventilation response to CO2 inhalation. The peripherally acting GABAB agonist, 3-APPi had no effect on ventilation. These findings demonstrate that the respiratory depressant effects of baclofen are due to activation of CNS GABAB receptors and indicates that only GABAB receptor agonists that penetrate into the CNS may cause respiratory depression. PMID- 7773532 TI - Unexpected prosecretory action component of loperamide at mu-opioid receptors in the guinea-pig colonic mucosa in vitro. AB - 1. In a voltage clamp setting (Ussing chamber), the antidiarrhoeal drug, loperamide (Lop) slightly augmented prostaglandin E1 (PGE1) plus theophylline stimulated net chloride secretion above control values at low concentrations (10( 10) and 10(-9) M) but inhibited it at higher concentrations (10(-6) and 10(-5) M). The apparently weak prosecretory action component of Lop was turned into a clear cut antisecretory effect by pretreatment with 2 x 10(-7) M naloxonazine plus 10(-7) M CTOP-NH2 (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2), two selective mu opioid receptor antagonists. This indicates a prosecretory effect of loperamide at mu opioid receptors. The antisecretory effect of low Lop concentrations, uncovered by mu opioid receptor blockade, was prevented by additional blockade of kappa opioid receptors by 5 x 10(-9) M nor-binaltorphimine (nor-BNI). 2. The nonselective opioid antagonist, naloxone, at 10(-6) M did not significantly reduce either PGE1 plus theophylline-stimulated net chloride secretion in Lop-free controls or the antisecretory action of Lop. By contrast, the partial agonist ethylketocyclazocine (EKC), which activates kappa but blocks mu opioid receptors, concentration-dependently inhibited PGE1 plus theophylline stimulated net chloride secretion without any consistent prosecretory action component. Nor-BNI at 5 x 10(-8) M significantly blocked the antisecretory action of EKC. 3. It is concluded that, in the guinea-pig colonic mucosa under the present conditions, mu opioid receptors mediate enhancement and kappa opioid receptors inhibition of PGE1-stimulated net chloride secretion by low Lop concentrations. The two opposite actions are largely masked by superimposition. An opioid receptor-independent mechanism of action contributes to the antisecretory effect of Lop at high concentrations. PMID- 7773533 TI - Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B adrenoceptor subtype. AB - 1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies. 2. Incubation of rat aortic membranes with the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC: 10 microM) did not change the KD of [3H]-prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (Bmax). 3. Contractions of rat aortic strips to NA after CEC (50 microM for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nM). 4. The competitive antagonists prazosin, terazosin, (R)-YM-12617, phentolamine, 5-methylurapidil and spiperone inhibited contractions to NA with estimated pA2 values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively. 5. The affinity of the same antagonists for the alpha 1A- and alpha 1B- adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5 Methylurapidil and phentolamine were confirmed as selective for the alpha 1A adrenoceptors, whereas spiperone was alpha 1B-selective. 6. A significant correlation was found between the pA2 values of the alpha 1-adrenoceptor antagonists tested and their affinity for the alpha 1B-adrenoceptor subtype, but not for the alpha 1A-subtype. 7. In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by alpha 1B-adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the alpha 1-adrenoceptor population. PMID- 7773534 TI - Effects of the selective I1 imidazoline receptor agonist, moxonidine, on gastric secretion and gastric mucosal injury in rats. AB - 1. Previous reports of the effects of alpha 2-adrenoceptor stimulation on gastric secretion are inconsistent because it was not clear whether the compounds were activating alpha 2-adrenoceptors and/or newly described imidazoline receptors. In the present experiments, the effects of moxonidine, an I1-imidazoline receptor agonist and antihypertensive agent, on gastric secretion and on experimental gastric mucosal injury were examined. 2. Moxonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) potently inhibited basal (non-stimulated) gastric acid secretion in conscious rats with an ED50 of 0.04 mg kg-1. Two hours following administration of the highest dose of moxonidine (1.0 mg kg-1), gastric acid output was completely suppressed. Moxonidine also significantly increased intragastric pH, at the two highest doses. 3. The alpha 2-adrenoceptor agonist, clonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) decreased basal acid secretion at the lowest dose (37%) and at the highest dose (46%), while the intermediate dose did not affect gastric acid output. 4. In an ethanol-induced model of gastric mucosal injury, moxonidine decreased the length of lesions at the lowest and highest doses (0.01 and 1.0 mg kg-1) as well as the number of the lesions, at the highest dose (1.0 mg kg-1). 5. In pylorus-ligated rats, moxonidine significantly decreased acid secretion (all doses), total secretory volume (1.0 mg kg-1) as well as pepsin output (1.0 mg kg-1). 6. In comparison to clonidine, moxonidine appears to be a more potent anti-secretory and gastric-protective compound. These data indicate a potential role for imidazoline receptor agonists in the management of gastroduodenal diseases associated with hypertension. The relative contribution of the central and peripheral effects of moxonidine to these gastrointestinal actions remains to be determined. PMID- 7773535 TI - Effects of Bordetella pertussis toxin pretreatment on the antiarrhythmic action of ischaemic preconditioning in anaesthetized rats. AB - 1. Bordetella pertussis toxin, which catalyses the ADP-ribosylation of certain guanine nucleotide binding proteins (G proteins), thus functionally uncoupling them from associated receptors, was examined to determine whether it modified the antiarrhythmic effect of ischaemic preconditioning in anaesthetized rats. 2. Pertussis toxin (25 micrograms kg-1, i.p., 48 h prior to heart isolation) attenuated the negative chronotropic effect of acetylcholine (ACh) in rat isolated Langendorff perfused hearts. ACh (10 microM) reduced heart rate by 4% in hearts taken from pertussis toxin-treated animals, compared to a reduction of 57% in hearts taken from animals treated only with vehicle. 3. In anaesthetized rats, ischaemic preconditioning (a single 3 min occlusion of the left main coronary artery followed by 10 min reperfusion) had a pronounced antiarrhythmic effect during a subsequent 30 min period of regional myocardial ischaemia. Compared to hearts receiving only a 30 min period of left coronary occlusion, there was a reduced mortality (67% and 0% for control and preconditioned groups, respectively; P < 0.01) and decreased incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF). Pretreatment with pertussis toxin (25 micrograms kg-1, i.p., 48 h previously) did not modify the arrhythmias associated with a 30 min period of regional myocardial ischaemia, neither did it modify the reduction in mortality (from 56% to 0%; P < 0.05) associated with preconditioning. Furthermore, the decrease in total ventricular premature beat count induced by preconditioning seen in controls (from 427 +/- 130 to 95 +/- 45) was also seen in pertussis toxin-treated rats (from 252 +/- 190 to 57 +/- 25). 4. These results suggest that receptor coupling to pertussis toxin-sensitive G proteins is not necessary for the antiarrhythmic effect of ischaemic preconditioning in this model. PMID- 7773536 TI - Pharmacokinetic modelling of the haemodynamic effects of the A2a adenosine receptor agonist CGS 21680C in conscious normotensive rats. AB - 1. The aim of the present investigation was to determine the relationship between the blood concentration and haemodynamic effects of the adenosine A2a receptor agonist, CGS 21680C (the sodium salt of 2-p-(2-carboxyethyl)phenylethylamino-5'-N ethylcarboxamidoadeno sin e) in conscious normotensive rats. 2. Chronically cannulated rats were randomly assigned to three groups which received 300, 1000 or 3000 micrograms kg-1 (0.56, 1.9 or 5.6 mumol kg-1) of CGS 21680C intravenously over 15 min. The mean arterial blood pressure (MAP) and heart rate (HR) were monitored continuously during the experiment and serial arterial blood samples were taken for analysis of drug concentration. The ratio MAP/HR was also calculated, which may reflect changes in total peripheral resistance on the assumption that no changes in stroke volume occur. 3. For each individual rat the reduction in mean arterial pressure was related to the blood concentration according to the sigmoidal Emax model. The concentration-effect relationships were consistent for the different treatment groups. The potency based on free drug concentrations (EC50,u) was 5.8 ng ml-1 (11 nM) (mean +/- s.e.; n = 19) and correlated well with the reported adenosine A2a receptor affinity (Ki 19 nM). In comparison with the reduction in blood pressure, CGS 21680C exhibited a greater potency for the reduction of the ratio MAP/HR. 4. It is concluded that estimates can be obtained for the potency and intrinsic activity of adenosine A2a receptor agonists in vivo by pharmacokinetic-pharmacodynamic analysis of mean arterial pressure data in a rat model. In future studies, total peripheral resistance may also be useful as a pharmacodynamic parameter for A24 activation, provided that possible changes of the stroke volume are also assessed. PMID- 7773537 TI - Pertussis toxin-sensitive muscarinic relaxation in the rat iris dilator muscle. AB - 1. The effects of pertussis toxin (PTX) on contraction and/or relaxation induced by agonists or transmural nerve stimulation (TNS) were examined in the rat iris dilator and sphincter muscles. 2. TNS in the presence of phentolamine induced an atropine-sensitive biphasic response: initial contraction followed by relaxation in dilator muscles. Exogenously applied acetylcholine (ACh) elicited a large relaxation at low doses (3 microM or less) and a concentration at high doses. 3. Only the ACh-induced relaxation was affected by injection of PTX (10 ng) into the anterior eye chamber. Relaxation was decreased 12 h after injection and had completely disappeared after 24 h. Relaxation recovered in part 3 weeks and almost completely 8 weeks after PTX treatment. A gradual decrease in muscarinic relaxation in a dilator muscle was also observed in vitro after addition of PTX to the bathing solution. 4. The pA2 values of muscarinic blockers, pirenzepine, AF-DX 116, 4-DAMP, and himbacine for competitive antagonism to ACh-induced contraction were 7.14, 6.53, 9.03, and 6.80, respectively, in PTX-pretreated dilator muscles. These values are comparable to those obtained in parasympathectomized dilator muscles and may indicate involvement of M3 or M3 like receptors in muscle contraction. 5. Pretreatment with PTX did not significantly affect contraction induced by noradrenaline or 5-hydroxytryptamine or the relaxation induced by isoprenaline in dilator muscles. 6. In conclusion, among several agonist-induced responses in the rat iris dilator and sphincter muscles, only muscarinic relaxation in dilator muscle occurs via activation of PTX-sensitive GTP binding proteins. PMID- 7773538 TI - Characterization of endothelin receptors in rat renal artery in vitro. AB - 1. The aim of this study was to investigate the function and characteristics of endothelin receptors in rat main branch renal artery in vitro. 2. Endothelin(ET) 1 (mean EC50 = 9.8 nM) was approximately 12 fold more potent than ET-3 (mean EC50 = 120 nM) as a contractile agonist and produced a greater maximum response. In contrast, neither of the ETB receptor-selective agonists, alanine[1,3,11,15]ET-1 nor sarafotoxin S6c, (0.1 nM-1 microM), induced any contractile effect, or any relaxant effect in endothelium-intact preparations pre-contracted with the thromboxane A2 mimetic, U-46619. Sarafotoxin S6c (30 nM) also failed to induce any further contraction in tissues pre-contracted with an EC50 concentration of ET-1. 3. The ETA receptor-selective antagonist, BQ123, behaved as a weak and variable antagonist of the contractile effects of ET-1 (mean pA2 estimates in the range 5.8-6.3). In contrast, BQ123 antagonized ET-3 with a potency (mean pA2 = 7.6) consistent with its affinity for ETA receptors. Co-incubation of BQ123 (3 microM) with the putative ETB receptor-selective antagonist, IRL1038 (10 microM), produced no greater antagonism of ET-1 responses than was induced by BQ123 (3 microM) alone. 4. In conclusion, ETB receptors do not appear to be present in rat main branch renal artery. The contractile effects of ET-3 in this tissue seem to be mediated by ETA receptors. While ETA receptors partly mediate the contractile effects of ET-1, these data raise the possibility that a population of novel BQ123-insensitive endothelin receptors may also contribute to this response. PMID- 7773539 TI - Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta. AB - 1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. PMID- 7773540 TI - Modulation of NMDA effects on agonist-stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex. AB - 1. The ability of memantine (1-amino-3,5-dimethyladamantane) to antagonize the modulatory effects of N-methyl-D-aspartate (NMDA) on phosphoinositide turnover stimulated by muscarinic cholinoceptor- and metabotropic glutamate receptor agonists has been examined in neonatal rat cerebral cortex slices. 2. Memantine antagonized the inhibitory effect of NMDA (100 microM) on both total [3H] inositol phosphate ([3H]-InsPx) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) mass accumulations stimulated by carbachol (1 mM) with EC50 values of 21 and 16 microM respectively. 3. Memantine concentration-dependently antagonized (IC50 24 microM) the ability of NMDA (10 microM) to potentiate [3H]-InsPx accumulation in response to a sub-maximal concentration of the metabotropic glutamate receptor agonist, 1S,3R-ACPD (10 microM). 4. The small (approx. 3 fold), concentration dependent increase in [3H]-InsPx accumulation stimulated by NMDA was completely antagonized by the prototypic NDMA receptor-channel blocker, MK-801 (1 microM) at all concentrations of NDMA studied (1-1000 microM). In contrast, antagonism by memantine (100 microM) was observed only at low concentrations of NMDA (1-10 microM), whilst [3H]-InsPx accumulation stimulated by high concentrations of NMDA (300-1000 microM) was markedly enhanced by memantine. 5. Assessment of the incorporation of [3H]-inositol into inositol phospholipids revealed that memantine (100 microM) caused an approximate 2 fold increase in the labelling of phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. 6H.p.l.c. separation of [3H]-inositol (poly)phosphates demonstrated that whilst memantine (100 microM)alone had no significant effect on the accumulation of any isomer, it substantially altered the profile of accumulation stimulated by NMDA (1 mM), greatly facilitating accumulation of Ins(1,4,5)P3 and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4).7.These data provide evidence that memantine can antagonize the actions of NMDA in neonatal rat cerebral cortex slices in a manner consistent with this agent acting as a NMDA receptor-channel blocker. In addition, at least two further actions of memantine can be proposed. Memantine increases the rate of [3H]-inositol incorporation into the cellular inositol phospholipid fraction, without significantly stimulating phosphoinositide turnover. Furthermore, memantine can substantially alter patterns of inositol (poly)phosphates stimulated by NMDA, promoting the accumulation of the established and putative second messengers Ins(1,4,5)P3 and Ins(1,3,4,5)P4 which are not increased by NMDA in the absence of memantine. It is unknown whether these latter loci of memantine action contribute to known therapeutic actions of this agent. PMID- 7773541 TI - Effect of the vascular endothelium on noradrenaline-induced contractions in non pregnant and pregnant guinea-pig uterine arteries. AB - 1. The effect of pregnancy on noradrenaline-mediated contraction of guinea-pig uterine artery rings with both intact and denuded endothelium was investigated. 2. Noradrenaline (25 nM-100 microM) induced concentration-dependent contraction of non-pregnant and pregnant guinea-pig uterine arterial rings with intact endothelium with similar pD2 and maximal response values (non-pregnant: pD2 = 5.85 +/- 0.02, maximal response = 121 +/- 8.2%; pregnant: pD2 = 5.81 +/- 0.04, maximal response = 122 +/- 9.1%). Removal of endothelium did not affect noradrenaline-induced contractions in non-pregnant guinea-pig uterine artery (pD2 = 5.97 +/- 0.02, maximal response = 119 +/- 8.6%). In contrast, in arteries from pregnant guinea-pigs, removal of endothelium shifted concentration-response curve for noradrenaline to the left, without affecting maximal response value (pD2 = 6.36 +/- 0.03, maximal response = 120 +/- 9.0%). 3. The pKA values for noradrenaline were: 5.76 +/- 0.09 and 5.82 +/- 0.10 for non-pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively and 5.74 +/- 0.09 and 5.72 +/- 0.07 for pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively. 4. The receptor occupancy-response relationship for noradrenaline was linear for all types of vessels, except for pregnant guinea-pig uterine artery with denuded endothelium, since half-maximal response to noradrenaline was obtained with 44.8 +/- 6.9% (non-pregnant guinea pig uterine artery with intact endothelium), 43.3 +/- 6.1% (non-pregnant guinea pig uterine artery with denuded endothelium) and 44.3 +/- 6.3% (pregnant guinea pig uterine artery with intact endothelium) receptor occupancy. In pregnant guinea-pig uterine artery with denuded endothelium, occupancy-response relationship for noradrenaline was non-linear since half-maximal response to noradrenaline was obtained with 19.7 +/- 3.3% receptor occupancy. 5. NG monomethyl-L-arginine (100 microM) and indomethacin (10 microM) did not affect concentration-response curve for noradrenaline in guinea-pig uterine arteries, regardless of pregnancy status or endothelial condition. 6. In quiescent preparations, the alpha-adrenoceptor antagonists, prazosin (5-50 nM) and yohimbine (1-10 microM) produced parallel rightward shifts of the curves for noradrenaline and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following - log Kb values: prazosin vs. yohimbine 8.78 +/- 0.03 vs. 6.41 +/- 0.02 for non-pregnant guinea pig uterine artery with intact endothelium, 8.95 +/- 0.03 vs. 6.34 +/- 0.02 for non-pregnant guinea-pig uterine artery with denuded endothelium, 8.91 +/ 0.01 vs. 6.44 +/- 0.03 for pregnant guinea-pig uterine artery with intact endothelium and 9.07 +/- 0.01 vs. 6.52 +/- 0.03 for pregnant guinea-pig uterine artery with denuded endothelium.7. It is concluded that initially there is no difference in noradrenaline action between uterine arteries from non-pregnant and pregnant guinea-pigs, but after removal of the endothelium the pregnant guinea pig uterine artery is more sensitive to noradrenaline, which is related to increased receptor reserve for noradrenaline in this tissue. It is probable that relaxing factor derived from the endothelium mediates this effect, but it is unlikely to be nitric oxide or prostacyclin. Antagonist affinities and affinity of noradrenaline itself suggests that an identical subtype of alpha-adrenoceptor, probably the alpha 1 subtype, is involved in the noradrenaline-induced contraction of non-pregnant and pregnant guinea-pig uterine artery with or without endothelium. PMID- 7773542 TI - A new class of furoxan derivatives as NO donors: mechanism of action and biological activity. AB - 1. The mechanism of action and biological activity of a series of R-substituted and di-R-substituted phenylfuroxans is reported. 2. Maximal potency as vasodilators on rabbit aortic rings, precontracted with noradrenaline (1 microM), was shown by phenyl-cyano isomers and by the 3,4-dicyanofuroxan, characterized by a potency ratio 3-10 fold higher than glyceryl trinitrate (GTN). This effect was reduced upon coincubation with methylene blue or oxyhaemoglobin (10 microM). 3. The furoxan derivatives showing maximal potency as vasodilators were also able to inhibit collagen-induced platelet aggregation, with IC50 values in the sub micromolar range. 4. The furoxan derivatives were able to stimulate partially purified, rat lung soluble guanylate cyclase; among the most active compounds, the 3-R-substituted isomers displayed a higher level of stimulatory effect than the 4-R analogues. 5. Solutions (0.1 mM) of all the tested furoxans, prepared using 50 mM phosphate buffer, pH 7.4, (diluting 10 mM DMSO stock solutions) did not release nitric oxide (NO) spontaneously; however in presence of 5 mM L cysteine, a significant NO-releasing capacity was observed, which correlated significantly with their stimulation of the guanylate cyclase activity. PMID- 7773543 TI - The inhibition of CYP enzymes in mouse and human liver by pilocarpine. AB - 1. Pilocarpine is a cholinomimetic natural alkaloid. Its interactions with testosterone hydroxylations, coumarin 7-hydroxylase (COH), dimethylnitrosamine N demethylase (DMNA), pentoxyresorufin O-dealkylase (PROD) and 7-ethoxyresorufin O deethylase (EROD), which are indicative of the activities of cytochrome P4502A5 (CYP2A5) or 6, 2E1, 2B, 1A, were examined in mouse and human liver microsomes. 2. In mouse liver microsomes the IC50 values of pilocarpine were 6 microM for COH and testosterone 15 alpha-hydroxylase (T15 alpha OH) activities, 4 microM for PROD, approximately 100 microM for DMNA and testosterone 6 beta-hydroxylase (T6 beta OH) activities and > 1 mM for EROD activity. 3. In human liver microsomes, the IC50 value for COH was 6 microM and for DMNA 10 microM; T15 alpha OH and PROD activities were not detectable but T6 beta OH and testosterone 16 beta/2 beta hydroxylase activities were moderately inhibited (IC50 70 microM). 4. These results suggest that pilocarpine has (i) a high affinity towards phenobarbitone inducible CYP2A4/5 and CYP2B activities in mouse liver, (ii) a high affinity towards CYP2A6 in human liver microsomes and (iii) a moderate affinity towards CYP3A enzyme(s) in both microsomal preparations. 5. The low IC50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes. PMID- 7773544 TI - The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver I2 imidazoline-preferring receptors. AB - 1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate I2 imidazoline-preferring receptors in the rat brain and liver after chronic treatment with various irreversible and reversible monoamine oxidase (MAO) inhibitors. 2. Chronic treatment (7-14 days) with the irreversible MAO inhibitors, phenelzine (1-20 mg kg-1, i.p.), isocarboxazid (10 mg kg-1, i.p.), clorgyline (3 mg kg-1, i.p.) and tranylcypromine (10 mg kg-1, i.p.) markedly decreased (21-71%) the density of I2 imidazoline-preferring receptors in the rat brain and liver. In contrast, chronic treatment (7 days) with the reversible MAO-A inhibitors, moclobemide (1 and 10 mg kg-1, i.p.) or chlordimeform (10 mg kg-1, i.p.) or with the reversible MAO-B inhibitor Ro 16 6491 (1 and 10 mg kg-1, i.p.) did not alter the density of I2 imidazoline preferring receptors in the rat brain and liver; except for the higher dose of Ro 16-6491 which only decreased the density of these putative receptors in the liver (38%). 3. In vitro, phenelzine, clorgyline, 3-phenylpropargylamine, tranylcypromine and chlordimeform displaced the binding of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors from two distinct binding sites. Phenelzine, 3-phenylpropargylamine and tranylcypromine displayed moderate affinity (KiH = 0.3-6 microM) for brain and liver I2 imidazoline-preferring receptors; whereas chlordimeform displayed high affinity (KiH = 6 nM) for these receptors in the two tissues studied, Clorgyline displayed very high affinity for rat brain (KiH = 40 pM) but not for rat liver I2 imidazoline-preferring receptors (KiH = 169 nM). 4. Preincubation of cortical or liver membranes with phenelzine (10-4 M for 30 min) did not alter the total density of I2 imidazoline-preferring receptors, indicating that this irreversible MAO inhibitor does not irreversibly bind to I2 imidazoline-preferring receptors. In contrast, preincubation with 10-6 Mclorgyline reduced by 40% the Bmax of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors.5. Chronic treatment (7 days) with the inducers of cytochrome P-450 enzymes phenobarbitone (40 or 80 mg kg-1, i.p.), 3 methylcholanthrene (20 mg kg-1, i.p.) or 2-methylimidazole (40 mg kg-1, i.p.) did not alter the binding parameters of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors.The compound SKF 525A, a potent inhibitor of cytochrome P-450 enzymes which forms a tight but reversible complex with the haemoprotein, completely displaced with moderate affinity (KiH = 2-10 microM)the specific binding of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors. Preincubation of total liver homogenates with 3 x 10-4 M phenelzine in the presence of 10-3 M NADH, a treatment that irreversibly inactivates the haeme group of cytochrome P-450, did not reduce the density of liver I2 imidazoline preferring receptors. These results discounted a possible interaction of [3H] idazoxan with the haeme group of cytochrome P-450 enzymes.6. Together the results indicate that the down-regulation of I2 imidazoline-preferring receptors is associated with an irreversible inactivation of MAO (at least in the brain) that is not related either to the affinity of the MAO inhibitors for I2 imidazoline preferring receptors or to an irreversible binding to these putative receptors. These findings indicate a novel effect of irreversible MAO inhibitors in the brain and suggest a new target for these compounds that could be of relevance in the treatment of depression, a disease in which an increased density of brain I2 imidazoline-preferring receptors has been reported. PMID- 7773545 TI - Interacting roles of nitric oxide and ATP in the pulmonary circulation of the rat. AB - 1. The potentiating effect of NG-nitro-L-arginine methyl ester, (L-NAME) a nitric oxide synthesis inhibitor, on responses of the rat pulmonary vascular pressure (PVP) to purinoceptor agonists was examined. 2. At a constant flow of 23 ml min-1 the PVP was 22.4 +/- 2.5 mmHg (n = 15), and treatment with 100 microM L-NAME for 15 min was without effect on the PVP. After the tone was raised with 28 nmol 9,11 dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U-46619), the PVP was 29.4 +/- 3.3 mmHg and treatment with 100 microM L-NAME was still without effect on the PVP. It appears that there is a graded release of nitric oxide in response to different levels of steady shear stress and in our experimental model the threshold for detection was not reached under basal conditions. 3. In contrast, when the circulation was challenged with 30 s step, additive increases in flow between 11 and 50 ml min-1 (n = 8), treatment with 100 microM L-NAME produced a significant (P < 0.05) increase in PVP suggesting that changes in flow derived forces evoke the release of nitric oxide. This was evident for flow rates above 30 ml min-1. 4. In preparations in which tone was raised with U-46619, a dose of 1 x 10(-8) mol ATP or 2-meSATP evoked a drop in PVP while alpha,beta meATP produced an increase in PVP under constant flow of 23 ml min-1. After treatment with 100 microM L-NAME, all three purinoceptor agonists evoked an increase in PVP. The increase in Pvp evoked by alpha, beta-meATP was not affected by L-NAME. These results suggest that P2Y-purinoceptor stimulation evokes the release of nitric oxide to produce vasodilatation.5. Under conditions of constant flow and basal pressure, 100 microM L-NAME significantly (P<0.05)potentiated the increase in Pvp evoked by 1 x 10-6 mol ATP, although the increase evoked by 1 x 10-8 mol (alpha,beta-meATP, which was of similar magnitude, was not affected. These results indicate that a blockade of evoked nitric oxide release is responsible for the potentiation of the increase in Pvp evoked by ATP.6. This study shows that, while nitric oxide does not appear to be released in the pulmonary circulation of the rat under constant flow conditions, nitric oxide release evoked by purinoceptor agonists attenuates increases in pulmonary vascular pressure. PMID- 7773547 TI - Pharmacological characterization of RS 25259-197, a novel and selective 5-HT3 receptor antagonist, in vivo. AB - 1. The pharmacological effects in vivo, of RS 25259-197, a selective 5-HT3 receptor antagonist, have been investigated. 2. In anaesthetized rats, RS 25259 197, administered by the intravenous, intraduodenal or transdermal route, dose dependently inhibited the von Bezold-Jarisch reflex induced by 2-methyl 5-HT (ID50 = 0.04 micrograms kg-1, i.v., 3.2 micrograms kg-1, i.d. and 32.8 micrograms per chamber, respectively). In this regard, when administered intraduodenally, RS 25259-197 was more potent and exhibited a longer duration of action than either ondansetron or granisetron. 3. In conscious ferrets, RS 25259-197, administered intravenously or orally, dose-dependently inhibited emesis induced by cisplatin. The ID50 estimates of RS 25259-197 were 1.1 micrograms kg-1, i.v. and 3.2 micrograms kg-1, p.o. In this respect, RS 25259-197 was more potent than ondansetron and equipotent with granisetron. 4. In conscious dogs, RS 25259-197, administered intravenously or orally, dose-dependently inhibited emesis induced by cisplatin (ID50 = 1.9 micrograms kg-1, i.v. and 8.5 micrograms kg-1, p.o.), dacarbazine (ID50 = 4.1 micrograms kg-1, i.v. and 9.7 micrograms kg-1, p.o.), actinomycin D (ID50 = 4.9 micrograms kg-1, i.v. and 2.5 micrograms kg-1, p.o.) and mechlorethamine (ID50 = 4.4 micrograms kg-1, i.v. and 3.0 micrograms kg-1, p.o.). Against each of the emetogenic agents, RS 25259-197 was very much more potent than ondansetron. When tested at equi-effective intravenous doses against cisplatin-induced emesis in dogs, RS 25259-197 had a longer duration of anti emetic activity (7 h) than ondansetron (4 h). At doses up to and including 1000 microg kg-1, p.o., neither RS25259-197 nor ondansetron was capable of inhibiting apomorphine-induced emesis.5. At doses up to 1000 microg kg-1, i.v., RS 25259-197 produced no meaningful haemodynamic changes in anaesthetized dogs.6. In summary, RS 25259-197 is a novel, highly potent and orally active 5-HT3 receptor antagonist in vivo. With respect to its anti-emetic activity, RS 25259-197 appears to be a significant improvement over ondansetron in terms of potency and duration of action. PMID- 7773546 TI - The interaction of RS 25259-197, a potent and selective antagonist, with 5-HT3 receptors, in vitro. AB - 1. A series of isoquinolines have been identified as 5-HT3 receptor antagonists. One of these, RS 25259-197 [(3aS)-2-[(S)-1-azabicyclo[2.2.2]oct-3-yl] 2,3,3a,4,5,6-hexahydro- 1- oxo-1H-benzo[de]isoquinoline-hydrochloride], has two chiral centres. The remaining three enantiomers are denoted as RS 25259-198 (R,R), RS 25233-197 (S,R) and RS 25233-198 (R,S). 2. At 5-HT3 receptors mediating contraction of guinea-pig isolated ileum, RS 25259-197 antagonized contractile responses to 5-HT in an unsurmountable fashion and the apparent affinity (pKB), estimated at 10 nM, was 8.8 +/- 0.2. In this tissue, the -log KB values for the other three enantiomers were 6.7 +/- 0.3 (R,R), 6.7 +/- 0.1 (S,R) and 7.4 +/- 0.1 (R,S), respectively. The apparent affinities of RS 25259-197 and RS 25259-198, RS 25233-197 and RS 25233-198 at 5-HT3 receptors in membranes from NG-108-15 cells were evaluated by a [3H]-quipazine binding assay. The -log Ki values were 10.5 +/ 0.2, 8.4 +/- 0.1, 8.6 +/- 0.1 and 9.5 +/- 0.1, respectively, with Hill coefficients not significantly different from unity. Thus, at these 5-HT3 receptors, the rank order of apparent affinities was (S,S) > (R,S) > (S,R) = (R,R). 3. RS 25259-197 displaced the binding of the selective 5-HT3 receptor ligand, [3H]-RS 42358-197, in membranes from NG-108-15 cells, rat cerebral cortex, rabbit ileal myenteric plexus and guinea-pig ileal myenteric plexus, with affinity (pKi) values of 10.1 +/- 0.1, 10.2 +/- 0.1, 10.1 +/- 0.1 and 8.3 +/- 0.2, respectively. In contrast, it exhibited low affinity (pKi <6.0) at 28 other receptors in binding assays, including adrenoceptors (alpha1A, alpha 1B, alpha2A, alpha 2B ,beta1, beta2), muscarinic (M1-M4), dopamine (D1, D2), opioid and other 5-HT(5-HTlA, 5-HTlD, 5-HT2C, 5-HT4) receptors.4. RS 25259-197 was tritium labelled (specific activity: 70 Ci mmol-1) and evaluated in pharmacological studies. Saturation studies with [3H]-RS 25259-197 in membranes from NG-108-15 and cloned homomeric a subunits of the 5-HT3 receptor from N1E-1 15 cells expressed in human kidney 293E1 cells,revealed an equilibrium dissociation constant (Kd) of 0.05 +/- 0.02 and 0.07 +/- 0.01 nM, and Bmax of610 +/- 60 and 1068 +/- 88 fmol mg-1, respectively. Competition studies in NG-108-15 cells indicated a pharmacological specificity entirely consistent with labelling a 5 HT3 receptor, i.e. RS 25259-197> granisetron> (S)-zacopride> tropisetron> (R) zacopride> ondansetron> MDL 72222.5. In contrast to the majority of radioligands available to label 5-HT3 receptors, [3H]-RS 25259-197 labelled a high affinity site in hippocampus from human post-mortem tissue with an equilibrium dissociation constant (Kd) of 0.15 +/- 0.07 nM and density (BmaX) of 6.8 +/- 2.4 fmol mg-1 protein. Competition studies in this tissue indicated a pharmacological specificity consistent with labelling of a 5-HT3receptor.6. Quantitative autoradiographic studies in rat brain indicated a differential distribution of 5 HT3receptor sites by [3H]-RS 25259-197. High densities of sites were seen in nuclear tractus solitaris and area postrema, a medium density in spinal trigeminal tract, ventral dentate gyrus and basal medial amygdala,and a low density of sites in hippocampal CAl, parietal cortex, medium raphe and cerebellum.7 In conclusion, the functional, binding and distribution studies undertaken with the radiolabelled and non-radiolabelled RS 25259-197 (S,S enantiomer) established the profile of a highly potent and selective5-HT3 receptor antagonist. PMID- 7773548 TI - Rapid degradation of endothelin-1 by an enzyme released by the rat isolated perfused mesentery. AB - 1. In vivo the effects of endothelin-1 (ET-1) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24.11, deamidase or carboxypeptidase A. Here, using as a model the isolated perfused mesenteric arterial bed of the rat, we have examined the involvements of these enzymatic activities in the vascular responses to ET-1. 2. Samples of Krebs buffer which had been recirculated through the mesenteric arterial bed for 30 min rapidly destroyed the activity of ET-1 as assessed either by bioassay on rings of rat thoracic aorta or by high performance liquid chromatography (h.p.l.c.). For instance, after 15 min incubation with the recirculated-Krebs solution (recirc-K) the contraction induced by 3 x 10(-9) M ET 1 was reduced by more than 90%. Contractions induced by sarafotoxin 6b (3 x 10( 9) M) were similarly suppressed by preincubation with recirc-K whereas those to Arg-vasopressin (3 x 10(-9) M) were unaffected. 3. The degradation of ET-1 by recirc-K was prevented by 1,10-phenanthroline (10(-3) M), abolished by heating the recirc-K solution to 90 degrees C for 15 min, and reduced by EGTA (5 x 10(-3) M) or ET-1(16-21) (10(-5) M). For instance, in the presence of ET-1(16-21) (n = 6) the contraction induced by ET-1 was reduced by only 40% after 15 min incubation with recirc-K buffer. Leupeptin (3 x 10-4 M), dichloroisocoumarin(5 x 10-5 M), phenylmethyl-sulphonyl fluoride (10-3 M), a combination of bacitracin (300 mg ml-1),bestatin (10-5 M), captopril (10-5 M), phosphoramidon (10-4 M) and thiorphan (10-4 M) or Polypep (aproprietary protein digest) did not inhibit the degradation of ET-1 by recirc-K.4. In experiments examining directly the vascular responses of the isolated perfused mesentery of the rat, the addition of cumulative concentrations of ET-1 to the recirculating Krebs solution caused small concentration-dependent increases in perfusion pressure. The inclusion of ET-1(16-2l), ET-1(17-21), or ET-1(18-21) (10-5M) greatly potentiated these responses, but not those to Arg-vasopressin or methoxamine.The effects of 1,10 phenanthroline or EGTA could not be examined in this system because these agents both depressed non-specifically the vasoconstrictor responses of the mesenteric vascular bed.5. Thus, the rat mesentery releases an enzyme that very rapidly destroys ET-1 or the very closely related peptide, sarafotoxin 6b but not Arg vasopressin. This enzyme is most probably a metallopeptidase because of its sensitivity to inhibition by 1,10-phenanthroline or EGTA. It is particularly interesting that a simple vascular bed such as the mesentery produces such a powerful endothelin metabolising enzyme. It is tempting, therefore, to speculate that the endothelin degrading enzyme active at neutral pH that- we have found is important in the metabolism of ET-1 throughout the vasculature. PMID- 7773549 TI - Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. AB - 1. Islets from normal mice were used to test the acute effects of genistein, a potent tyrosine kinase inhibitor, on stimulus-secretion coupling in pancreatic beta-cells. 2. Genistein produced a concentration-dependent (10-100 microM), reversible, increase of insulin release. This effect was marginal on basal release or in the presence of non-metabolized secretagogues, and much larger in the presence of glucose or other nutrients. The increase in insulin release caused by 100 microM genistein was abolished by adrenaline or omission of extracellular Ca2+. It was not accompanied by any rise of cyclic AMP, inositol phosphate or adenine nucleotide levels. 3. Although genistein slightly inhibited ATP-sensitive K+ channels, as shown by 86Rb efflux and patch-clamp experiments, this effect could not explain the action of the drug on insulin release because the latter persisted when ATP-sensitive K+ channels were all blocked by maximally effective concentrations of glucose and tolbutamide. Genistein was also effective when ATP-sensitive K+ channels were opened by diazoxide and the beta-cell membrane depolarized by 30 mM K, but ineffective in the presence of diazoxide and normal extracellular K. 4. Genistein paradoxically decreased Ca2+ influx in beta cells, as shown by the inhibition of glucose-induced electrical activity, by the inhibition of Ca2+ currents (perforated patches) and by the lowering of cytosolic [Ca2+]i (fura-2 technique). Genistein thus increases insulin release in spite of a lowering of [Ca2+]i in beta-cells. 5. Daidzein, an analogue of genistein reported not to affect tyrosine kinases, was slightly less potent than genistein on K+ and Ca2+ channels, but increased insulin secretion in a similar way. Three other tyrosine kinase inhibitors, tyrphostin A47, herbimycin A and an analogue of erbstatin variably affected insulin secretion.6. Genistein exerts a number of heretofore unrecognized effects. The unusual mechanisms, by which genistein increases insulin release in spite of a decrease in beta-cell [Ca2+]i and without activating known signalling pathways, do not seem to result from an inhibition of tyrosine kinases. PMID- 7773550 TI - Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea-pigs. AB - 1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, cardiac M2 receptor function in vitro and bronchial responsiveness to histamine in vivo were evaluated. 2. Sensitivity to inhaled histamine was increased 3.1 fold and 1.6 fold after the early and late allergic reactions (i.e. at 5 h and 23 h after a single ovalbumin challenge), respectively. At 23 h after the last of four allergen challenges, executed on four consecutive days, bronchial hyperresponsiveness to histamine was diminished to 1.3 fold. 3. After the early response, there was no change in cardiac muscarinic M2 receptor function, since in left atria pD2 (-log EC50) and Emax values of pilocarpine and pKB values of AQ RA 741, a selective M2 receptor antagonist, were not significantly different from controls (unchallenged sensitized animals), and this also applied to methacholine pD2 values for muscarinic M3 receptors in tracheal smooth muscle. 4. Prejunctional inhibitory muscarinic M2 autoreceptors in airway smooth muscle were markedly dysfunctional after the early allergic response, since potentiation of electrically evoked twitch contractions of tracheal preparations by low concentrations of the M2-selective muscarinic receptor antagonists, gallamine, methoctramine, AQ-RA 741 and AF-DX 116, which is the result of M2 receptor blockade, was clearly and significantly diminished compared to controls. However, after the late response, both in single and repeatedly challenged animals, twitch potentiation was not significantly different from and similar to controls, indicating restoration of M2 receptor function during the late allergic reaction.5. It is concluded that dysfunction of muscarinic M2 autoreceptors in the airways of sensitized and challenged guinea-pigs is already present after the early allergic reaction, and that it has recovered after the late response. Since histamine-induced bronchoconstriction involves vagal pathways, the present results suggest that bronchial hyperresponsiveness to histamine is partly due to M2 auto receptor dysfunction, leading to increased release of acetylcholine. PMID- 7773551 TI - Acute effects of the beta 3-adrenoceptor agonist, BRL 35135, on tissue glucose utilisation. AB - 1. The acute effects of BRL 35135 (BRL) on tissue glucose utilisation index (GUI) in vivo were investigated in anaesthetized rats by use of 2-deoxy-[3H]-glucose. 2. Intravenous injection of BRL caused a dose-dependent increase in GUI in skeletal muscle, and white and brown adipose tissue; plasma insulin and fatty acid concentrations were also increased. Chronic treatment with BRL added to the diet caused a 34 fold increase in basal GUI of brown adipose tissue (BAT), but had no effect on GUI in other tissues. After chronic treatment, the acute tissue response to an intravenous maximal dose of BRL had disappeared completely in all tissues apart from the soleus muscle. 3. A high dose (20 mg kg-1) of the non selective beta-antagonist, propranolol, inhibited the acute effect of BRL on GUI in BAT, but failed to affect GUI in muscle. A lower dose (1 mg kg-1) of the antagonist also inhibited the BAT response, but had little or no effect on the response in Type I (working) muscles such as soleus and adductor longus (ADL), and potentiated the response in Type II (non-working) muscles such as tibialis and extensor digitorium longus (EDL). 4. A low dose (1 mg kg-1) of the selective beta 1-antagonist, atenolol, had no effect on the BRL response but the same dose of the selective beta 2-antagonist, ICI 118551, potentiated significantly the effect of BRL on GUI in most muscles without altering plasma insulin levels. 5. It is concluded that: (i) the heterogeneous tissue responses of different muscle fibre types in the presence of P-antagonists indicates that BRL affects muscle GUI directly, in addition to effects mediated by increases in plasma insulin concentration; (ii) the resistance of the BRL response to conventional P adrenoceptor antagonists implicates an atypical adrenoceptor mediating the GUI response in skeletal muscle, but this may not be identical to the adipose tissue P3-adrenoceptor; (iii) the potentiation of BRL responses by ICI 118551 indicates an inhibitory P2-adrenoceptor-mediated component in the muscle GUI response to BRL. PMID- 7773554 TI - Proceedings of the British Pharmacological Society meeting. 14-16 December 1994. Abstracts. PMID- 7773553 TI - Anaesthetic modulation of nicotinic ion channel kinetics in bovine chromaffin cells. AB - 1. We have investigated the action of the anaesthetics methoxyflurane, methohexitone and etomidate on the nicotinic acetylcholine receptor channel of bovine adrenal chromaffin cells using the whole cell patch clamp technique. 2. Spectral analysis of macroscopic currents evoked by 25 microM carbachol revealed that each of the agents tested reduced the lifetime of the channel open state in a dose-dependent manner. The whole cell current was inhibited in a concentration dependent fashion by each agent. 3. Channel gating parameters were calculated from single channel studies and the results used to test models explaining the modulation of nicotinic acetylcholine receptor channels by anaesthetics. 4. Each of the agents studied reduced the mean channel open time in a concentration dependent manner. Anaesthetic concentrations reducing mean open time by 50% were: 370 microM methoxyflurane, 30 microM methohexitone or 23 microM etomidate. 5. Methohexitone and etomidate produced an increase in the number of brief closures within bursts, while no such increase was observed with methoxyflurane. Despite these inter-burst gaps, mean burst length was reduced by each of the agents tested. 6. It is concluded that a simple sequential blocking model fails to account for the action of these anaesthetics. An extended model, in which blocked channels can close, may be applicable. PMID- 7773552 TI - Role of endothelium in the human uterine arteries during normal menstrual cycle. AB - 1. The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2. Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E2) (follicular and luteal phases, E2 = 131.9 +/- 15.9 pg ml-1, n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 181.1 +/- 9.0 pg ml-1, n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P < 0.05 and P < 0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3. Correlation between the maximum response to ACh and the plasma E2 was highly significant (gamma = 0.8142, P < 0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4. Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh- and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was significantly inhibited by methylene blue.5. The A23187-induced relaxation was hardly affected by methylene blue or L-NOARG in group III,but was partially inhibited by these agents in group II. The effect of indomethacin in inhibiting the A23187 induced-relaxation was most potent (58.9%) in group III and least (16.9%) in group I.6. There were no histological changes in 14 cases out of 18 (groups I and II), but very slight intimal thickening was observed in 4 cases in group I. On the other hand, severe intimal thickening was observed in all 6 cases in group III.7. These results indicate that, in human uterine artery strips, ACh and A23187 cause endothelium dependent relaxations, which are mediated mainly through EDRF/NO in group I, mainly prostacyclin(PGI2) in group III, or both in group II. It is suggested that lack of the production/release of EDRF/NO and/or of interaction between EDRF/NO and PGI2 might play a role in the formation of intimal thickening in human uterine arteries. PMID- 7773555 TI - Encapsulated PC12 cell transplants into hemiparkinsonian monkeys: a behavioral, neuroanatomical, and neurochemical analysis. AB - Four cynomolgus monkeys were trained on a hand reaching task and then rendered hemiparkinsonian with an intracarotid injection of n-methyl 4 phenyl 1,2,3,6, tetrahydropyridine (MPTP). Performance on this task with the limb contralateral to the MPTP injection was significantly impaired following the lesion. Three monkeys received implants of polymer-encapsulated containing PC12 cells into the caudate nucleus and putamen. One monkey received identical implants of empty capsules and served as a control. After a transient improvement, limb use in the control monkey dissipated and returned to post-MPTP disability. Two of the three PC12 cell grafted monkeys recovered performance on the hand reach task to near normal levels for up to 6.5 mo posttransplantation. Capsules retrieved from the monkeys who recovered limb function postimplantation contained numerous viable PC12 cells that continued to release levodopa, basal dopamine, and potassium evoked dopamine. In contrast, capsules retrieved from the PC12 cell-grafted monkey which did not recover limb use on the hand reach task contained few cells which secreted negligible or undetectable levels of levodopa and dopamine. Interestingly, functional disability was not reinstated following removal of the capsules. Neuroanatomical and neurochemical evaluation of the grafted striatum did not reveal a host-derived sprouting response of catecholaminergic or indolaminergic fibers. These data indicate that xenografts of PC12 cells can survive for up to 6.5 mo in nonimmunosuppressed monkeys when immunoisolated via polymer encapsulation. Moreover, these cells continue to secrete high levels of levodopa and dopamine and induce recovery of motor function in parkinsonian nonhuman primates. PMID- 7773556 TI - Synthetic vascular grafts seeded with genetically modified endothelium in the dog: evaluation of the effect of seeding technique and retroviral vector on cell persistence in vivo. AB - Unique characteristics of endothelium make it an attractive target cell for gene transfer. Genetically modified endothelial cells (ECs) seeded on synthetic vascular grafts offer the potential to control neointimal hyperplasia, decrease graft thrombogenicity and improve small diameter graft patency. This study addresses the issue of synthetic vascular graft colonization with endothelial cells transduced with noninducible retroviral marker genes in the dog. Autologous endothelial cells were enzymatically harvested and transduced with either the bacterial NeoR gene or human growth hormone gene using retroviral vectors. All transduced cells were positive by polymerase chain reaction (PCR) amplification for the transduced gene sequence prior to graft seeding. Transduced ECs were seeded on Dacron grafts (n = 3) preclotted with autologous blood. These grafts exhibited complete endothelialization at times from 250 to 360 days. Recovered DNA, however, was negative for the transduced gene sequence when analyzed by PCR and Southern blotting. Expanded polytetrafluoroethylene (ePTFE) was evaluated (n = 8) using several different cell seeding protocols. Grafts were seeded at 3 densities (ranging from 6 x 10(3) to 1.5 x 10(5) cells/cm2) and 2 different adherence times. Seeding substrate was also evaluated. Grafts were either preclotted with whole blood or incubated with 20 or 120 micrograms/ml fibronectin for 60 min. Graft biopsies were evaluated from 2 to 52 wk. Limited endothelialization was present in 4 dogs as early as 2 wk, but never progressed to full luminal coverage. The remaining dogs failed to ever exhibit any luminal EC adherence. Two dogs with limited EC coverage had positive DNA by PCR for the NeoR gene sequence at 2 and 3 wk. In contrast to transduced EC's, nontransduced EC colonization of ePTFE was complete at 2 wk when seeded under conditions that transduced cells had failed to persist. Neither seeding density, adherence time, seeding substrate or retroviral vector used influenced the uniformly poor graft coverage seen with transduced cells. Results of this study indicate that despite successful gene transfer using 4 different retroviral vectors, transduced endothelial cells seeded under varying conditions appear altered in their ability to stably adhere and colonize synthetic vascular grafts in vivo. PMID- 7773557 TI - Repeated intraportal hepatocyte transplantation in analbuminemic rats. AB - The optimal site for implantation of isolated hepatocytes has not been established. We have developed a novel technique which allows repeated infusion of hepatocytes into the portal system via an indwelling catheter. Seven Nagase Analbuminemic rats (NAR) underwent single intraportal infusion of 2 x 10(7) isolated normal albumin-producing rat hepatocytes. Another seven NAR rats underwent placement of indwelling catheters into the portal venous system via the gastroduodenal vein. Each of them received six batches of 5 x 10(6) normal albumin producing hepatocytes. Seven control NAR rats were infused repeatedly (intraportally) with saline only. Plasma albumin (ELISA) showed significant increase in experimental animals and was more pronounced (p < 0.05) in rats transplanted repeatedly than in those given a single dose of cells. Immunohistochemical staining of the liver sections confirmed the presence of transplanted albumin producing hepatocytes. Rats transplanted with a single large batch of isolated hepatocytes showed liver tissue damage, whereas those subjected to repeated cell infusions had normal liver histology. We have developed a novel intraportal transplantation method which allows successful engraftment of a large number of isolated hepatocytes. PMID- 7773558 TI - Protective effect of glutathione (GSH) over glutathione monoethyl-ester (GSH-E) on cold preservation of isolated rat liver cells. AB - Hepatocyte suspensions provide a rapid method to determine how hypothermic storage affects liver cell metabolism and viability. We investigated whether reduced Glutathione (GSH) inclusion into a modified University of Wisconsin (UW) solution, has a protective effect over Glutathione derivatives, such as Glutathione-monoethylester (GSH-E), when suspensions of hepatocytes are cold stored for several days. Isolated rat liver cells were cold preserved 96 h in UW, UW plus 3 mM GSH and UW plus 3 mM GSH-E. During the cold storage, not significant changes in cell viability were observed, but the total Glutathione content was higher in systems with extracellular GSH over those with GSH-E or without. After cold storage, the liver cells were gently resuspended in Krebs-Henseleit-1% Albumin and used for 120 min of normothermic (37 degrees C) incubation. We evaluate the functional response of the cells measuring the exclusion of Trypan Blue (TBE). This response was clearly different in preserved cells in presence of GSH. These results indicate a protective role of extracellular Glutathione, due to an accumulation of it, rather than the derivative, for hepatic cell during the cold storage in UW solutions. And also, it is possible to extend experiments with hepatocytes from a single cell isolation over 4 or more consecutive days. PMID- 7773560 TI - Genetics and molecular biology. PMID- 7773559 TI - Porcine repeat element DNA: in situ detection of xenotransplanted cells. AB - Using a digoxygenin-labelled DNA probe derived from the porcine repeat element PRE-1, we have developed a protocol for the detection of transplanted porcine islets and hepatocytes against a background of murine host tissue. Analysis of this probe by Southern blotting indicated that PRE-1 hybridizes to pig genomic DNA but not to human or mouse DNA. On tissue sections, hybridizing probe was detected using alkaline phosphatase-conjugated antidigoxygenin antibody visualized with 5-bromo-4-chloro-3-indolyl-phosphate/4-nitro-blue tetrazolium chloride (BCIP/NBT) substrate. We have demonstrated sensitive and highly specific staining of porcine nuclei in fixed, paraffin embedded tissue sections, and have applied the technique to detect porcine pancreatic islets and hepatocytes transplanted into murine kidney and spleen. Application of this technique include detection of transplanted cells or organs across the variety of xenogeneic barriers. PMID- 7773561 TI - Nutrition. PMID- 7773562 TI - Genetics and molecular biology. PMID- 7773563 TI - Lipid metabolism. PMID- 7773564 TI - Hyperlipidaemia and cardiovascular disease. PMID- 7773565 TI - Atherosclerosis: cell biology and lipoproteins. PMID- 7773566 TI - Therapy and clinical trials. PMID- 7773567 TI - The VLDL receptor: wayward brother of the LDL receptor. AB - The VLDL receptor binds lipoproteins that contain apolipoprotein E and consists of five functional domains that resemble the LDL receptor. Although the LDL- and VLDL-receptor genes are located on different chromosomes, their gene structure and organization are almost the same. Despite the presence of sterol regulatory element-1-like sequences in the VLDL-receptor gene, the transcription of the gene is not down-regulated by sterols. The VLDL-receptor messenger RNA is highly expressed in tissues that actively metabolize fatty acids as their source of energy. The physiological role of the chicken cognate of the VLDL receptor has been revealed recently, but its function in mammals is still debatable. PMID- 7773568 TI - Bile acid transporters. AB - The sodium-dependent bile acid transporters and sodium-independent organic anion transporters are integral membrane glycoproteins that function in the enterohepatic circulation of bile acids. The recent cloning and expression of different classes of bile acid transporters have provided insights into their structure and molecular mechanism. PMID- 7773569 TI - Genetics and molecular biology. PMID- 7773570 TI - Apolipoprotein B messenger RNA editing: insights into the molecular regulation of post-transcriptional cytidine deamination. AB - A site-specific cytidine deamination (cytidine to uridine) in nuclear apolipoprotein B messenger RNA creates a translational stop codon that produces apolipoprotein B48. This process is mediated by an enzyme composed of distinct subunits, including apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 and additional complementation factors. The apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 is expressed ubiquitously in the rat, but is largely confined to the small intestine in humans and rabbits. By contrast, complementation activity is present in tissues that neither express nor edit apolipoprotein B messenger RNA. PMID- 7773571 TI - Biosynthesis and metabolism of lipoprotein (a). AB - Significant advances have been made over the past year toward understanding the pathways of lipoprotein (a) biosynthesis and metabolism. Transcriptional and post translational mechanisms have been identified as important determinants of plasma lipoprotein (a) levels. Assembly of lipoprotein (a) has been shown to be an extracellular event that occurs on the hepatocyte cell surface. The development of lipoprotein (a) transgenic mice has provided a valuable model to study the metabolism of lipoprotein (a). PMID- 7773572 TI - Transforming growth factor-beta: the key to understanding lipoprotein(a)? AB - Most large studies of the blood parameters that act as risk factors for myocardial infarction, stroke and atherosclerosis have identified elevated circulating levels of lipoprotein(a) as an important risk factor. Lipoprotein(a) consists of an LDL particle that is covalently bound to the distinguishing protein component apolipoprotein(a). Ever since apolipoprotein(a) was cloned in 1987 and the marked sequence homology to plasminogen was noted, mechanisms for the atherogenic activity of lipoprotein(a), based on the competitive inhibition of plasminogen activity, have been proposed. However, with the availability of transgenic mice expressing both human apolipoprotein(a) and lipoprotein(a), recent studies have demonstrated that lipoprotein(a) acts to inhibit plasminogen activation in vivo. One consequence of this is reduced activation of the cytokine transforming growth factor-beta, an important regulator of vessel wall structure. PMID- 7773573 TI - Apolipoprotein E: impact of cytoskeletal stability in neurons and the relationship to Alzheimer's disease. AB - Apolipoproteins E3 and E4 exert differential effects on neuronal growth in vitro. Apolipoprotein E3 supports neurite extension, whereas apolipoprotein E4 does not. These isoform-specific effects may influence the stability of the cytoskeleton and may account for the association of the apolipoprotein E4 isoform with the pathogenesis of Alzheimer's disease. PMID- 7773574 TI - Yolk precursor transport in the laying hen. AB - The fully grown chicken oocyte, better known as the egg yolk, is a giant single cell that contains, besides bona fide cytoplasm, endocytosed, serum-derived lipoproteins and minor components that are essential for normal embryo development. The transport of bulk lipoproteins, micronutrients and morphogens to oocytes, in parallel with the maintenance of somatic homeostasis, is achieved by the cell-specific expression of receptors and subtle differences in the ligand structure that determine their target sites. Lipoprotein metabolism is the paradigm for these regulatory principles. In this review, the laying hen is described as a model system for intercellular transport that has uncovered new aspects of the biological rationale for the simultaneous expression of closely related genes in a single organism. PMID- 7773575 TI - Lipoprotein and receptor interactions in vivo. AB - A substantial number of animal models aimed at the genetic dissection of lipid metabolism have been generated recently. Transgenic and knockout mice, in which the receptors or apolipoproteins are overexpressed or destroyed, combined with virus-mediated gene transfer in vivo have advanced our understanding of the complex physiological and pathophysiological processes involved in lipid metabolism, including hepatic lipoprotein uptake and the formation of atherosclerotic lesions. PMID- 7773576 TI - The annual meeting and 35th symposia of the Japanese Society of Plant Physiologists. Matsue, Japan, March 28-30, 1995. Abstracts. PMID- 7773577 TI - Sepsis and septic shock. I. Definitions and pathophysiology. AB - Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy. Understanding the pathophysiology of sepsis enables clinicians to institute rational intervention directed towards the pathophysiological mechanisms. This article reviews definitions of sepsis and offers a brief overview of ist pathophysiology. Current knowledge on the pathophysiological mechanism of cytokines and modulation of systemic cytokine levels during sepsis and septic shock is discussed. The important role of cytokines in sepsis and septic shock may require more detailed investigations of the cytokine pathophysiological network. PMID- 7773579 TI - Management of cancer anorexia/cachexia. AB - Cancer anorexia/cachexia is a common clinical problem that substantially impacts upon the quality of life and survival of affected patients. Extensive investigations have not supported the use of either enteral or paternal hyperalimentation for such patients. Despite positive pilot trial reports, large randomized studies have been unable to demonstrate a clinically defensible role for either pentoxifylline, cyproheptadine, or hydrazine sulfate for patients with anorexia. Multiple placebo-controlled, randomized, double-blind, clinical trials have demonstrated that corticosteroids do have appetite-enhancing properties in patients suffering from cancer anorexia/cachexia, but none of these studies has demonstrated weight gain. In comparison, multiple studies have demonstrated that the progestational agent, megestrol acetate, has both appetite-enhancing and weight-promoting properties. PMID- 7773581 TI - Intensive care in anticancer centres: an international inquiry. AB - Intensive care is increasingly frequently used in the management of cancer patients. In order to determine whether and how critical-care facilities are used specifically for these patients, we performed a world-wide inquiry in anticancer centres. We mailed a questionnaire to 141 centres and received 84 responses (57.5%). There was at least one oncological intensive care-unit (ICU) in 59 hospitals (70%). The majority of the ICU were found in the European institutions. Data were obtained concerning the ICU organisation, the medical team, the nursing staff, the critical-care techniques and the anticancer treatments performed. Medical ICU appeared to be managed by physicians and nurses often qualified in both intensive care and oncology. These data suggest that oncological intensive care should be part of the training of oncologists and intensivists. PMID- 7773578 TI - Sepsis and septic shock. II. Treatment. AB - Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy. This article reviews current therapy of septic shock including immunotherapy and further possibilities of septic shock treatment. The role of cytokines, their inhibitors and antibodies to endotoxin is mentioned. Although these treatments hold much promise for the future, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended. PMID- 7773580 TI - The management of hypercalcemia of malignancy. AB - Hypercalcemia (HCM) occurs in 10-15% of all malignancies, predominantly in patients with solid tumors. This metabolic complication leads to significant morbidity and impairment of quality of life. Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid hormone-related peptide and several cytokines secreted by tumors. The osteoclast plays a central role as the final common pathway through which these hormones and cytokines act to cause bone lysis. These findings have led to the development of new treatment strategies. Foremost among these has been the introduction of agents such as the newer bisphosphonates and gallium nitrate, which are potent inhibitors of osteoclast-mediated bone resorption. The clinician can now choose from an array of therapeutic approaches based on a consideration of the mechanisms of action, individual clinical circumstances, efficacy, toxicities and costs of available agents. In addition to their use in the management of HCM, non toxic drugs that effectively inhibit osteoclast function, such as the bisphosphonates, are playing an emerging role in the palliative treatment of the more common clinical problems of painful lytic bone metastases and osteoporosis. PMID- 7773582 TI - Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study. AB - The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS). PMID- 7773583 TI - Combined management in the treatment of epidoxorubicin extravasation. A case report. AB - Inadvertent extravasation during intravenous antitumor therapy is not an unusual complication and can cause damage ranging from minor erythema to severe local necrosis. The appropriate management of these iatrogenic accidents as a part of supportive care in oncology has been addressed by several experimental studies, but there has been little clinical study and no conclusive evidence on the best therapeutic strategies to adopt. The case reported here of a patient suffering from severe soft-tissue injury caused by extravasation of epidoxorubicin demonstrates the usefulness of a combined management (medical, surgical and rehabilitative) in the appropriate care of extravasation. PMID- 7773585 TI - Euthanasia not only for terminal illness. PMID- 7773584 TI - Intensive care support in oncology: a contradiction? PMID- 7773587 TI - Epstein-Barr virus immortalizing genes. AB - Epstein-Barr virus (EBV) is linked to several types of human cancer and immortalizes human B cells very efficiently; at least six viral genes are required for this. The mechanism by which EBV immortalizes cells is particularly interesting because its immortalization genes are not obvious homologues of those of other DNA tumour viruses. PMID- 7773586 TI - Intensive care and oncology. AB - Intensive care is increasingly used in the management of cancer patients. The main reasons for admitting a cancer patient to an intensive-care unit are postoperative recovery, critical complications of the cancer disease and its treatment, the administration and monitoring of intensive anticancer treatment, and acute disease unrelated to cancer or its treatment. The present review is focused on the prognosis of critically ill cancer patients, on the description of the types of complications requiring intensive care, on specific aspects of the application of critical-care techniques in cancer patients, on ethical considerations and on ICU organization in the context of oncology. PMID- 7773588 TI - Viral potentiation of bacterial superinfection of the respiratory tract. AB - Virus infections of the respiratory tract predispose it to bacterial superinfections. Epidemiological studies, clinical evidence of viral-bacterial co infection and animal models of such interactions suggest a time course of events and several mechanisms by which viral potentiation may occur. It appears that structural and functional disruption of the respiratory mucosal epithelium is a major contributor to the synergistic effects of superinfection. PMID- 7773590 TI - Intestinal epithelial cells as watchdogs for the natural immune system. AB - Intestinal epithelial cells secrete a spectrum of chemoattractant and proinflammatory cytokines after invasion by bacteria. We suggest the novel concept that epithelial cells not only act as a mechanical barrier to invasive bacteria, but that they also signal the presence of invasive pathogens to the mucosal immune and inflammatory cells. PMID- 7773589 TI - HIV retrotransposon activity and the immunopathogenesis of AIDS. AB - This article presents the new hypothesis that HIV retrotransposon insertional mutagenesis induces genomic effects that bring about immune dysfunction through disruption, deletion or rearrangement of the genome of the host. This activity may be augmented by the action of most, if not all, the cofactors of HIV-induced disease. PMID- 7773591 TI - The antiviral effects of nitric oxide. PMID- 7773592 TI - Identification of bacterial genes that contribute to survival and growth in an intracellular environment. PMID- 7773593 TI - Haemophilus ducreyi: pathogenesis and protective immunity. AB - Haemophilus ducreyi is the etiological agent of chancroid, a sexually transmitted disease that is common in developing countries and that has characteristic genital mucocutaneous lesions. The adherence and growth of bacteria on the surface of eukaryotic cells, and the production of cytotoxin(s) result in cell damage that may be responsible for the development of ulcers. The mechanisms for protective immunity in chancroid are unclear, but both humoral and cell-mediated mechanisms may be involved. PMID- 7773594 TI - Infection by bovine papillomavirus and prospects for vaccination. AB - Infection with bovine papillomavirus (BPV) results in the onset of benign proliferative lesions that usually regress spontaneously through a cell-mediated immune response. Occasionally, warts persist as benign tumours or progress to squamous-cell carcinomas. Vaccines that prevent or cure BPV infection provide a model for the formulation of vaccines against human papillomavirus. PMID- 7773595 TI - The fungal cell wall as a drug target. AB - Fungal infections are increasingly common and, in certain vulnerable patients, can be serious and even life threatening. The fungal cell wall, a structure with no mammalian counterpart, presents an attractive therapeutic target. Inhibitors of the synthesis of one cell-wall component, beta-(1,3)-glucan, are currently under development as antifungal and antipneumocystis agents. PMID- 7773596 TI - Stump the experts. Apocrine hidrocystoma. PMID- 7773597 TI - Soft tissue augmentation. A review. AB - BACKGROUND: Soft tissue augmentation is one of the most sought after cosmetic procedures around the world. It has been performed for centuries, but only in this decade or so have materials become available that allow effective therapy. OBJECTIVE: This review article discusses the use of materials for soft tissue augmentation as to where they fit into the overall scheme of treating the aging face, as well as the benefits and side effects of each, and how to maximize the use of these various materials. RESULTS: The materials reviewed with regard to both efficacy and safety of those currently on the market as well as those currently in research. CONCLUSION: With the understanding of the role of soft tissue augmentation in the overall treatment of the aging face as well as risk factors and ways to minimize the side effects, dermatologic surgeons can reach the goal of effectively treating patients with these materials. PMID- 7773598 TI - Postoperative wound infection rates in dermatologic surgery. AB - BACKGROUND: Multiple factors related to the nature of the surgical procedure can influence the risk of wound infection in dermatologic surgery. Despite that, wound infection rates in dermatologic surgical procedures are believed to be low. OBJECTIVE: This study was conducted: 1) to determine wound infection rates in Mohs and excisional surgery; and 2) to investigate if factors such as lesion type, anatomic location, postoperative defect size, number of Mohs stages required to achieve a tumor-free plane, and the type of reconstructive procedure influence the rate of surgical wound infections. RESULTS: Wound infection rate for 530 Mohs procedures and 517 excisions combined was 2.29%, falling within the predicted range for "clean" surgical procedures. In addition, Mohs procedures performed on the ear as well as large postoperative defects were found to have a higher rate of wound infections. CONCLUSION: Dermatologic surgery can be safely performed in an outpatient setting without a significant risk of infection. Certain anatomic sites, such as the ear, as well as size of postoperative defect, are important factors in predicting the risk of postoperative wound infection. PMID- 7773599 TI - Repetitive pulsed dye laser treatments improve persistent port-wine stains. AB - BACKGROUND: Approximately 50-75% lightening of port-wine stains is achieved within two to three treatments with pulsed dye laser therapy, but the incidence of complete clearing is variable. OBJECTIVE: This study was designed to: 1) assess the ability of continued repetitive pulsed dye laser treatments to further lighten persistent port-wine stains; 2) evaluate the factors contributing to the resistance of port-wine stains to laser therapy; and 3) determine the relative risk of adverse effects following repetitive treatments to the same area. METHODS: A retrospective photographic analysis was performed of 69 patients that failed to achieve greater than 75% lesional lightening within nine treatment sessions. The percentage improvement was assessed by comparing the degree of lightening at the last treatment to that of the midway point of treatment. RESULTS: Significant improvement in port-wine stain lightening, from the midway to last treatment, was seen in patients who had 10-25 repetitive treatments. CONCLUSION: Repetitive treatments with the pulsed dye laser can lead to improvement in the overall lightening of persistent port-wine stains without an increased risk of adverse effects. PMID- 7773600 TI - The isolated frontal forelock. AB - BACKGROUND: The progression and extent of male pattern baldness is statistically unpredictable. OBJECTIVE: An approach to the patient with male pattern baldness is suggested, which results in a product that changes appearance in a positive way, is natural, requires no maintenance, and does not deconstruct with progression of alopecia. METHODS AND RESULTS: A technique is described for transplantation of the frontal forelock allowing creation of a soft anterior zone and a dense posterior component. CONCLUSION: The utilization of donor hair to create a transplanted forelock will eventuate in a product that maintains naturalness regardless of the progression or extent of future hair loss. PMID- 7773601 TI - Aluminum oxide crystal microdermabrasion. A new technique for treating facial scarring. AB - BACKGROUND: Aluminum oxide crystal microdermabrasion, a newly developed technique, has the advantages of less bleeding, fewer complications, better compliance, and no need for local anesthesia or high surgical skill in comparison with traditional dermabrasion. OBJECTIVE: To demonstrate the effectiveness of this new technique in the treatment of facial scarring. METHODS: A total of 41 patients were treated by this technique during the past 2 years (July 1992 to June 1994). RESULTS: All patients treated had good to excellent clinical improvement with 9.10 mean treatment sessions. CONCLUSION: From our experience and results, we think aluminum oxide crystal microdermabrasion is a safe surgical procedure and will be a good supplement to traditional dermabrasion especially in this era of HIV infection. PMID- 7773602 TI - Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles. AB - BACKGROUND: A new method of subcuticular underming for the treatment of depressed cutaneous scars and wrinkles is introduced. OBJECTIVE: To define the newly coined term "Subcision" and to describe this minor surgical procedure for treating depressed scars and wrinkles. METHODS: A tri-beveled hypodermic needle is inserted through a puncture in the skin surface (hence, "incisionless" surgery), and its sharp edges are maneuvered under the defect to make subcuticular cuts or "-cisions." RESULTS: The depression is lifted by the releasing action of the procedure, as well as from connective tissue that forms in the course of normal wound healing. CONCLUSION: This technique is useful in treating a variety of cutaneous depressions, including scars and wrinkles. PMID- 7773603 TI - Antibiotic prophylaxis in cutaneous surgery. AB - BACKGROUND: Postoperative wound infections, endocarditis, and late contamination of prosthetic implants are potential complications of cutaneous surgery. OBJECTIVE: To review current American Heart Association guidelines and their application to cutaneous surgery, and to determine how practicing physicians approach this problem. METHOD: Surveys were sent to dermatologists to determine what kind of preoperative screening was being done and how antibiotics were being used. RESULTS: The most common indications for prophylaxis were manipulation of infected tissue in patients undergoing any procedure, and any procedure in a patient with a prosthetic heart valve. Some respondents used antibiotic prophylaxis for all procedures, while others never used antibiotics in any surgical procedure. Cephalosporins and erythromycin were the most commonly used antibiotics and they were usually given orally, one dose before and one dose after surgery. CONCLUSION: Scientific literature supports the use of antibiotic prophylaxis for endocarditis in two situations: 1) surgical procedures on infected tissue in patients with a high risk cardiac lesion; and 2) any surgical procedure in a patient with a prosthetic heart valve. Our survey suggests that the majority of dermatologists obtain pertinent medical history and use appropriate antibiotic prophylaxis in these two situations. But the survey also suggests that antibiotic prophylaxis is used in a variety of situations where indications for use are not as clear, and sometimes prophylaxis is not used when it should be. PMID- 7773604 TI - Informed consent and informed refusal. AB - BACKGROUND: This article continues our medicolegal series that addresses issues affecting current dermatology practice. Informed consent and informed refusal have become cornerstones of modern American healthcare, and can serve to facilitate communication and trust between physician and patient. METHODS: A format with an initial discussion of legal concepts is followed by hypothetical problems and a review of actual cases to illustrate the principles of informed consent and informed refusal. RESULTS: A valid informed consent from a competent patient should be obtained before initiating most dermatologic treatment. When a competent patient refuses a recommended medical test or procedure, the physician should make sure the patient understands the potential negative consequences of refusal. Some form of written documentation in the medical record is advised in either situation. CONCLUSION: Failure to obtain a patient's informed consent prior to beginning treatment or failing to obtain an informed refusal before accepting a patient's decision to forego a test or procedure may subject the dermatologist to multiple later allegations, most commonly negligence. PMID- 7773605 TI - Closure of conchal defects. The hinged retroconchal island flap with overlying cutaneous transposition flap. AB - BACKGROUND: Conchal defects secondary to surgical procedures or trauma often cannot be closed primarily. OBJECTIVE: Tissue transfer for closure of defects must be tension free and not create a postauricular sulcus too shallow. METHODS: A retroconchal island flap provides such a closure. A rhomboid transposition flap used to provide closure of the donor site retains the depth of the posterior sulcus. RESULTS: The closure of the defect heals well within 4-6 weeks even in presence of scar tissue from multiple prior surgeries. CONCLUSION: The retronconchal island flap is a simple, reliable technique to close the defect of the concha without sacrificing the natural depth of the posterior sulcus. PMID- 7773606 TI - Bovine collagen products and gelatin sponges for hemostasis in punch biopsies of HIV-1+ patients. PMID- 7773607 TI - Laser hair transplantation. PMID- 7773608 TI - Carbamylation decreases the cytotoxicity but not the drug-carrier properties of polylysines. AB - The charge density of Poly(D-lysine) was reduced by the carbamylation of the lysyl residues with potassium cyanate. A decrease in the charge density of poly(D lysine) by 25% and 50% reduced the cytotoxicity of the ligand to cultured L929 cells by a 5-, and a 20 to 25-fold level, respectively, as estimated by using either the viability or the protein assay. The uptake of cyanate-modified poly(D lysine) ligands in cultured L929 cells was not reduced, while the uptake of poly(D-lysine)/Heparin complex was reduced by 80%, as compared to that of unmodified poly(D-lysine). The in vivo biodistribution of cyanate-modified poly(D lysine) ligands in the lungs and the liver of mice was not altered in comparison to that of unmodified poly(D-lysine), whereas the poly(D-lysine)/Heparin complex was only accumulated in the liver but not in the lungs. The data in this paper indicate that a 50% decrease in the positive charge density of poly(D-lysine) reduces the toxicity, but not the carrier potential of this polycationic ligand. PMID- 7773610 TI - Effect of iontophoretic patterns on in vivo antidiuretic response to desmopressin acetate administered transdermally. AB - The effects of concentration, amperage and duration on the antidiuretic response induced by iontophoretic delivery of desmopressin acetate (DDAVP) were examined using a diabetes insipidus model in rats. A higher current density brought about a larger and longer antidiuretic response. Prolonged iontophoretic duration caused an overdose. Repeated short iontophoretic treatments with lower current density maintained a constant response with a short lag time and a rapid disappearance of pharmacological response immediately after cessation of the final treatment. This type of iontophoresis substantially reduced the inter subject variability of response as compared to the response using an intranasal route of administration. PMID- 7773609 TI - Cholesteryl-conjugated phosphorothioate oligodeoxynucleotides modulate CYP2B1 expression in vivo. AB - 5' cholesteryl-conjugated phosphorothioate oligodeoxynucleotides with sequence complementary to the rat CYP2B1 mRNA were evaluated in adult male Sprague-Dawley rats for their pharmacokinetic properties, toxicity, and ability to modulate CYP2B1 expression in vivo. Following intraperitoneal administration of 35S labelled oligodeoxynucleotides, volume of distribution for the phosphorothioate was 0.33 l/kg while the 5' cholesteryl-conjugate oligodeoxynucleotide was 0.12 l/kg. The elimination half-life was 23.2 and 55.4 hrs for cholesteryl-modified and unmodified oligodeoxynucleotides, respectively. Cholesteryl-conjugate oligodeoxynucleotide toxicity was detected at a dose of 1.0 mg/kg and consisted primarily of midzonal liver cell enlargement and increased total RNA. Hexobarbital sleep times, a measure of CYP2B1 enzyme activity in vivo, increased from 21.9 minutes in saline-treated animals to 29.5 minutes in cholesterol oligodeoxynucleotide-treated animals. A significant decrease in liver microsomal pentoxyresorufin O-dealkylase enzyme activity, a CYP2B1/2 specific assay, was observed but not a change in p-nitrophenol hydroxylase activity, a specific CYP2E1 assay. These data indicate that in vivo modulation of the CYP2B1 gene can be accomplished with synthetic phosphorothioate oligodeoxynucleotides in a sequence-specific manner. Further, cholesteryl conjugation to the 5' end of the oligodeoxynucleotide enhanced potency despite lesser bioavailability. PMID- 7773611 TI - Liposomal alpha-tocopherol alleviates the progression of paraquat-induced lung damage. AB - The present study was carried out to investigate the efficacy of liposome associated alpha-tocopherol in treating pulmonary damage caused by paraquat exposure. alpha-Tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) or plain liposomes were intratracheally instilled into the lungs of rats 24 h after paraquat treatment (20 mg/kg, ip); treated animals were killed 8, 24 or 48 h after administration of the liposomal preparations. Lungs of animals exposed to paraquat were extensively damaged as evidenced by an increase in lung weight and decreases in pulmonary angiotensin converting enzyme and alkaline phosphatase activities. Also, paraquat treatment resulted in a significant reduction in glutathione (GSH) concentration in the lung and an elevation in microsomal lipid peroxidation levels, as measured by the formation of diene conjugates. Treatment of paraquat-injected rats with plain liposomes did not significantly alter paraquat-induced changes of all parameters examined. On the other hand, treatment of rats with alpha-tocopherol liposomes, 24 h after paraquat administration, resulted in a significant increase in pulmonary alpha-tocopherol concentrations as well as a reduction in paraquat-induced changes in lipid peroxidation, GSH concentration, and lung angiotensin converting enzyme and alkaline phosphatase activities. The results of the present study suggest that alpha-tocopherol, administered directly to the lung in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of paraquat-induced lung injury. PMID- 7773612 TI - Starch microspheres induce pulsatile delivery of drugs and peptides across the epithelial barrier by reversible separation of the tight junctions. AB - Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm. PMID- 7773613 TI - Further studies on targeted DNA transfer to cells using a highly efficient delivery system of biotinylated transferrin and biotinylated polylysine complexed to streptavidin. AB - Conjugates consisting of biotinylated transferrin and biotinylated poly-L-lysine attached to streptavidin have been prepared and found to transfer luciferase plasmid DNA very efficiently to HeLa cells in the presence of chloroquine. Transfection was dependent on (i) use of biotinylated short chain polylysine containing 70 lysine residues, (ii) biotinylated transferrin containing 1-2 biotin moieties, (iii) reaction of biotinylated transferrin with streptavidin followed by isolation of the resulting conjugate on Sephadex G-200 and (iv) interaction of streptavidin-biotinylated transferrin with biotinylated polylysine giving a complex suitable for DNA transfection. It was found that if the above sequence of steps resulting in the formation of streptavidin-biotinylated transferrin/biotinylated polylysine was followed without isolation of intermediate conjugates by Sephadex G-200 chromatography, pRSVL DNA transfer was still very efficient. Transfer of luciferase DNA by the streptavidin conjugates and subsequent expression of luciferase activity was almost completely inhibited by excess free transferrin, showing that gene transfer was through the transferrin receptor pathway via receptor-mediated endocytosis. The streptavidin (bio2-transferrin) bio10-pLys70 conjugate used in the present experiments was approximately one hundred times more efficient in pRSVL DNA transfection with the HeLa cells than the previously described avidin-pLys460 (bio-transferrin) complex. PMID- 7773614 TI - Synthesis and the stereoselective enzymatic hydrolysis of flurbiprofen-basic amino acid ethyl esters. AB - Ethyl esters of flurbiprofen L-arginine (FP-Arg-OH), flurbiprofen L-lysine (FP Lys-OH) and flurbiprofen p-guanidino-L-phenylalanine (FP-GPA-OH) were synthesized and then the release of flurbiprofen enantiomers from these derivatives in the presence of trypsin (Tp), carboxypeptidase B (CPB) and carboxypeptidase Y (CPY) were examined in order to evaluate their availability as prodrugs for flurbiprofen (FP). The ester bonds of the three racemic FP derivatives were hydrolyzed by Tp at about 3 to 20 times the rates of N-benzoyl-L-arginine ethyl ester (Bz-Arg-OEt), a specific substrate for Tp. (R)-FP was released faster than (S)-FP by either CPB or CPY from both FP-Arg-OH and FP-Lys-OH. On the other hand, FP-GPA-OH was not hydrolyzed at all by CPB and the hydrolysis rate of this compound by CPY was very slow. (S)-Flurbiprofen L-arginine ethyl ester ((S)-FP Arg-OEt) was separated from (R)-FP-Arg-OEt by high-performance liquid chromatography. A comparison of the kinetic parameters for the tryptic hydrolysis of the two optically active FP-Arg-OEt diastereomers and those of Bz-Arg-OEt suggested that the orientation of the scissile bond in each diastereomer to the catalytic center of Tp is more favorable than that of Bz-Arg-OEt. However, no significant difference was found between the kinetic parameters for the two diastereomers, suggesting that the orientational difference between (S)-FP and (R)-FP in the diastereomers does not have any effect on the tryptic hydrolysis of the ester bond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773615 TI - Chirality and drug targeting: pros and cons. AB - The theoretical basis of stereoselectivity in drug targeting in terms of eudismic ratio and quantitative structure-activity relationship has been presented. Specific examples of the advantages of using the correct stereoisomers (eutomers) rather than the distomers or racemic mixtures have been discussed. With the recent development of new methods of chiral synthesis and chiral analysis, it is not longer justifiable to continue to use racemic mixtures as therapeutic agents, unless it can be proven to be safe to do so. In the area of using peptides, proteins, glycoproteins and polysaccharides as therapeutic agents, mother nature has been very selective in choosing the optically active starting materials (Bradley, 1994), it is a necessity to design and test the proper optical isomer when a mimetic or antagonist compound is contemplated as a therapeutic agent. PMID- 7773616 TI - A non-ionic surfactant vesicle-in-water-in-oil (v/w/o) system: potential uses in drug and vaccine delivery. AB - An aqueous dispersion of niosomes (non-ionic surfactant vesicles) emulsified in an external oil phase forms the vesicle-in-water-in-oil (v/w/o) system described in this paper. The properties of the surfactant used to form the vesicles, the surfactant or surfactant mixture used to stabilize the emulsion and the nature of the oil phase can be changed to provide systems of different capacities for drug or antigen and different release characteristics. The same nonionic surfactant is used as the principle amphipile to form the niosomes and to stabilize the w/o emulsion, thus promoting stability by decreasing transfer of surfactant between the stabilizing monolayers and the vesicle bilayers. The in vitro release of carboxyfluoroscein and 5-fluorouracil encapsulated within the niosomes of the v/w/o system has been investigated, the nature of the oil phase and surfactant oil interactions being important in determining the rate of solute release. Initial studies of the system in vivo, as an adjuvant for tetanus toxoid, using cottonseed oil as the external oil phase, showed enhanced immunological activity over the free antigen or vesicles. PMID- 7773617 TI - Effect of calcium ions on the surface charge and aggregation of phosphatidylcholine liposomes. AB - The aggregation behaviour of multilamellar liposomes composed of egg phosphatidylcholine (EPC) and dipalmitoylphosphatidylcholine (DPPC) in the presence of varying concentrations of calcium ions has been studied by measuring changes in the particle size of liposome suspensions. Reversible aggregation occurred with both liposome preparations, showing a maximum rate at approximately 0.9 to 1.8 mM calcium chloride. At higher or lower concentrations aggregation was inhibited in the case of EPC suspensions or, for DPPC systems, occurred only slowly. Furthermore, the EPC systems showed more marked increases in size when aggregation occurred. The zeta potentials of both systems were negative in water, becoming positive on increasing the concentration of calcium ions. A reasonable correlation was found between calcium concentration corresponding to the minimum in initial zeta potential and that producing the greatest aggregation rate. PMID- 7773618 TI - Biotransformations in the regioselective deacetylation of polyphenolic peracetates in organic solvents. AB - Regioselectivity has been observed in the deacetylation of peracetates of polyphenolic aromatic ketones by lipases from porcine pancreas (PPL) and Candida cyclindracea (CCL) suspended in organic solvents. The deacetylation of acetoxyl groups at positions para and meta to the carbonyl (ketonic) group is favoured over the one at the ortho position. PMID- 7773619 TI - The specific inhibition of crystal growth of monohydrogen potassium L-tartrate by d-catechin. AB - Crystal growth of monohydrogen potassium L-tartrate in an ethanolic aqueous solution was specifically inhibited by d-catechin, but not by either its epimeric isomer at C3, l-epicatechin or by gallic acid and caffeic acid. 3D-Structure similarity search of d-catechin with two molecules of the tartrate and docking study of d-catechin with the crystal model of the tartrate suggested that d catechin mimics a structure consisting of the two tartrate molecules in the inhibition. Differences in the conformation of the catechol moieties of d catechin and l-epicatechin may explain the distinct inhibitory effects of the epimeric isomers. PMID- 7773620 TI - Molecular determinants of recognition and activation at the cerebellar benzodiazepine receptor site. AB - Semiempirical quantum mechanical and molecular mechanics calculations were carried out to identify and characterize the steric and electronic properties that modulate ligand recognition and activation of the cerebellar GABAA/benzodiazepine (BDZ) receptor. For this hypothesis development, thirteen compounds belonging to structurally diverse chemical families were selected for study. Among the compounds selected were nine that bind and four that do not bind with appreciable affinity to this receptor and some that are known agonists, antagonists and inverse agonists, as measured by their modulation of GABA (gamma aminobutyric acid) enhanced chloride ion flux in cerebellum. The stereoelectronic requirements for recognition deduced from commonalities among the ligands are the presence of at least two of three hydrogen bonding centers, and a lipophilic aromatic ring, in a specific spatial relationship. The results suggest that the selectivity for the cerebellar or Type I subtype, demonstrated by some of these ligands, could be failure to meet the requirements for binding at other receptors because of the absence of one of the proton accepting centers or the larger surface area and volume of these ligands. The requirement for activation, deduced from comparisons of agonist, antagonist, and inverse agonist properties is the presence of an electron accepting aromatic ring in a specific geometric arrangement with respect to the components of recognition. The validity of the '3D-Pharmacophore' developed was probed by using it for predictions of the behavior of 11 additional compounds not used for its development. PMID- 7773621 TI - Suksdorfin: an anti-HIV principle from Lomatium suksdorfii, its structure activity correlation with related coumarins, and synergistic effects with anti AIDS nucleosides. AB - Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937. Combinations of 1 and the anti-HIV nucleosides ddI and ddC demonstrated statistical synergy in inhibiting HIV-1 replication (ddC > ddI). However, the viral inhibition mediated by combining 1 with AZT was not statistically synergistic. Furthermore, the presence of suksdorfin did not antagonize the suppression mediated by the three nucleoside reverse transcriptase inhibitors. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity. PMID- 7773622 TI - Potential radioprotective agents--V. Melatonin analogs. Oral activity of p aminopropiophenone and its ethylene ketal. AB - Seven new amides of 5-methoxytryptamine were synthesized and tested for radioprotective activity in mice. One of them, the heptafluorobutyramide 4, is moderately active (57% survivors), the rest demonstrate little or no activity. Of twelve compounds that had been found to exhibit high radioprotective activity by ip injection, only two [p-aminopropiophenone (9) and its ethylene ketal 8] retain that high activity (92-95% survivors) when administered orally. Three are moderately active: p-aminobenzonitrile (10, 55%), 5-methoxytryptamine octanoic amide (11, 50%), and p-aminobenzophenone (12, 48%). PMID- 7773623 TI - Dialkylaminoalkyl esters of 2,2-diphenyl-2-alkylthioacetic acids: a new class of potent and functionally selective muscarinic antagonists. AB - The synthesis and pharmacological activity as muscarinic antagonists of a number of 2-alkylthio-2,2-diphenylacetic acid esters are reported. The compounds studied are potent muscarinic antagonists and many of them show from moderate to high selectivity toward M2 or toward M1 and M2 receptors when tested on tissues but lack selectivity on five muscarinic human receptors (m1-m5) cloned and expressed in CHO-K1 cells. As a consequence, the compounds behave as functionally selective antagonists. Those showing M2 selectivity appear to be good drug candidates for the treatment of cognitive disorders connected with central cholinergic deficit. PMID- 7773624 TI - The synthesis of novel HIV-protease inhibitors. AB - The syntheses, enzyme inhibition and antiviral activity of potent HIV-protease inhibitors containing novel beta-hydroxy ether and thioethers based on the transition state mimetic concept are discussed. PMID- 7773625 TI - Alpha-ketoamide Phe-Pro isostere as a new core structure for the inhibition of HIV protease. AB - Studies on the inhibition of HIV-1 protease utilizing a core isostere with replacement of the scissle bond for an alpha-amino-ketone have resulted in the development of an alpha-keto-amide isosteric replacement of the Phe-Pro scissle amide bond. The simple dipeptide isostere was shown to be a promising new core structure for the development of the enzyme inhibitors. The Ki of this core structure was determined to be 6 microM, compared to 230 microM and > 50 microM for the corresponding phosphinic acid and hydroxyethylamine isosteres. PMID- 7773626 TI - Synthesis and anti-cancer activity of 2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides. AB - A series of 2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides (2), have been synthesized and evaluated as anti-cancer agents. These compounds were designed as masked alpha-methylenecyclopentanones, which appear in many cytotoxic or anti-cancer natural products. Most of the synthesized compounds were found to be active towards various human cancer cell lines and many showed significant subpanel selectivity. For compounds containing the same alkylidene moiety (from C3 to C9), the dimethylaminomethyl analogs were more active than structures possessing morpholino-, pyrrolidino-, or piperidino-methyl groups. Alteration of the alkylidene moiety had little effect on anti-cancer potency. The mass spectrum of a glutathione adduct of 2h indicated that the mechanism of action for these anti-cancer agents may be related to the attack at the aminomethyl carbon atom by biological nucleophilic thiols. PMID- 7773627 TI - A new class of compounds, peptide derivatives of adenosine 5'-carboxylic acid, includes inhibitors of ATP receptor-mediated responses. AB - A new type of ligand for the study of P2-purinergic receptor subtypes was synthesized by combining and modifying conventional nucleoside chemistry with Fmoc solid phase peptide synthesis techniques. The tri- and tetra-aspartic acid derivatives of adenosine-5'-carboxylic acid (AdoCAsp3 and AdoCAsp4) were found to act as weak agonists at P2-purinergic receptors, (activated by ATP and UTP respectively) present on C6 glioma cells. AdoCAsp4 induced inositol 1,4,5 trisphosphate formation in the C6 cells with an EC50 of 73 microM. In addition, AdoCAsp4 was found to inhibit (IC50 approximately 80 microM) ATP-induced cytosolic [Ca2+] transients in these glioma cells. The glycine derivative, AdoCGly, increased evoked release of noradrenaline from mouse vas deferens slices, probably due to the blockade of presynaptic P2-autoreceptors. The possibility that aspartic, glutamic or gamma-carboxyglutamic residues may be used to replace phosphate groups on an ATP receptor ligand, opens up new ways in ligand design. PMID- 7773628 TI - Synthesis of 2-imidazolidinylidene propanedinitrile derivatives as stimulators of gastrointestinal motility--II. AB - In a previous paper, we reported that a novel ranitidine derivative 2 (fumarate: KW-5092), which had a 2-imidazolidinylidene propanedinitrile moiety (A), showed potent gastrointestinal motility enhancing activity. In order to obtain more potent gastrointestinal motility enhancing agents than compound 2 and to examine the effects of various substituents both at a nitrogen atom (B) in the 2 imidazolidinylidene propanedinitrile moiety and a basic nitrogen atom (C), compounds 5-29 were synthesized and evaluated for acetylcholinesterase (AChE) inhibitory activity and potentiating action on electrically stimulated contractions of guinea pig ileum. Introduction of alkyl, benzyl, aryl or acyl groups to the nitrogen (B) or (C), remarkably influenced both activities. Among these, compounds 14 and 15 showed more potent AChE inhibitory activity (IC50 = 6.7, 6.8 nM, respectively) than compound 2 and were active in potentiating action on the ileal contraction (EC30 = 9.5, 11 nM, respectively) together with a negligible histamine H2-receptor blocking property. Furthermore, these compounds were found to be more effective in the enhancement of gastrointestinal motility in anesthetized rabbits than compound 2. PMID- 7773629 TI - Neointimal fibrosis in vascular pathologies: role of growth factors and metalloproteinases in vascular smooth muscle proliferation. PMID- 7773630 TI - Collagen turnover in renal disease. PMID- 7773631 TI - Glomerular cell proteoglycans: their possible role in progressive glomerular disease. PMID- 7773632 TI - Human renal fibroblast cell lines (tFKIF and tNKF) are new tools to investigate pathophysiologic mechanisms of renal interstitial fibrosis. PMID- 7773633 TI - Myofibroblast differentiation during fibrosis. PMID- 7773634 TI - Integrin distribution in normal kidney and cultured human glomerular cells. PMID- 7773635 TI - Transforming growth factor beta (TGF-beta) regulates the matrix-associated plasminogen activator inhibitor 1 (PAI-1) in glomerular mesangial and epithelial cells. PMID- 7773636 TI - Increased fibronectin incorporation into extracellular matrix in response to platelet-derived growth factor is mediated by transforming growth factor beta. PMID- 7773637 TI - Opportunities for the discovery of novel therapies for fibrotic diseases. PMID- 7773638 TI - Renal scarring: a multi-organ approach to fibrosis. PMID- 7773639 TI - Pathways to renal fibrosis. PMID- 7773640 TI - Interstitial macrophages as mediators of renal fibrosis. PMID- 7773641 TI - Tissue inhibitor of the metalloproteinases and renal extracellular matrix accumulation. PMID- 7773642 TI - Role of the macrophage in the development of glomerulosclerosis. PMID- 7773643 TI - Matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases expression by tubular epithelia and interstitial fibroblasts in the normal kidney and in fibrosis. PMID- 7773644 TI - Pathogenesis, experimental manipulation and treatment of liver fibrosis. PMID- 7773645 TI - Pathogenesis of lung fibrosis and potential new therapeutic strategies. PMID- 7773646 TI - Analytical expression for the magic-angle spinning nuclear magnetic resonance line shape in the presence of the second-order quadrupole interaction for the non zero asymmetry parameter and large sample rotation frequency. AB - An analytical expression for the magic-angle spinning nuclear magnetic resonance (MAS NMR) line shape function for the non-zero asymmetry parameter and large sample rotation frequency has been derived using the time-independent part of the quadrupole transition energy based on the stationary perturbation theory. The averaging over Euler angles in the case of a powdered sample is also done analytically, which is so far implemented in the literature by a numerical simulation procedure. While the peak positions obtained from analytical and numerical averaging procedures agree well, the peak heights are significantly different, showing the need for an analytical solution for the averaging over Euler angles, as this would otherwise lead to erroneous values for the quadrupole parameters. The MAS NMR line shape function derived in this paper can be compared directly with the experimental MAS NMR spectrum for the large sample rotation frequency, and the values of the quadrupole parameters can be obtained. We have also described a method of evaluating the quadrupole parameters for the small sample rotation frequency, using the peak heights and peak separation of the central band of the experimental MAS NMR spectrum and the MAS NMR line shape function derived in the present paper. As an example, the quadrupole parameters for vitreous B2O3 are computed. PMID- 7773647 TI - 13C solid-state nuclear magnetic resonance and Fourier transform infrared studies of the thermal decomposition of cork. AB - The thermal decomposition of cork has been studied by Fourier transform infrared (FTIR) spectroscopy and 13C solid-state nuclear magnetic resonance (NMR) spectroscopy with cross-polarization and magic-angle spinning (CP-MAS), high power 1H decoupling (HPDEC) and cross-polarization depolarization-polarization (CPDP). Waxes and other soluble components of cork begin to decompose at ca. 150 degrees C. This is accompanied by partial decomposition of suberin, probably initiated at the points of attachment to the cell wall. The carbohydrates begin to decompose at ca. 200 degrees C. The decomposition of lignin begins at 250-300 degrees C, while suberin undergoes further degradation. Significant amounts of coke are formed in the process. At 400 degrees C cork has been transformed into coke with traces of partially decomposed suberin. The thermal decomposition of cork is dependent on the calcination time, particularly in the 200-350 degrees C range. PMID- 7773648 TI - Anomalous proton relaxation, rotational tunnelling and barriers to methyl group rotation in solid acetyl halides. AB - Rotational excitations of methyl groups attached to carbonyl in solid acetic acid, acetyl fluoride, acetyl chloride and acetyl bromide have been investigated by 1H nuclear magnetic resonance (NMR) relaxation times and field-cycling measurements at two frequencies and various temperatures. The tunnel splittings have been found to occur between 3.3 and 0.08 mu eV making quantum effects important for the relaxation behaviour. For the acetyl halides, similar tunnelling and NMR frequencies lead to an anomalous-looking temperature dependence of the relaxation rates. A consistent description by Haupt's equation is possible. The rotational potentials have been derived from the data and compared with those obtained from microwave spectra of the corresponding isolated molecules. The hindering potential is purely three-fold and the barrier is dominated by the functional group. PMID- 7773649 TI - Determination of spin parameters reflected in the nuclear magnetic resonance powder patterns for two equivalent 31P nuclei in Lawesson's reagent. AB - The nuclear magnetic resonance (NMR) powder patterns observed for the 31P spin pair in Lawesson's reagent (1) were analyzed. Using an efficient procedure, wide ranges of the spin parameters were examined to determine whether they might reproduce the experimental one-dimensional (1D) spectrum of the present A2 spin system. It was demonstrated that the parameters were not uniquely determined from the 1D powder pattern only, but a significant reduction of their uncertainties was realized using the two-dimensional (2D) powder pattern. The molecular structure of 1 was discussed in terms of the refined spin parameters. PMID- 7773650 TI - Multifield magic-angle spinning and double-rotation nuclear magnetic resonance studies of a hydrated aluminophosphate molecular sieve: AlPO4-H2. AB - AlPO4-H2 is a microporous hydrated aluminophosphate, structurally related to VPI 5, whose framework has highly elliptical 10-ring channels (2.9 x 7.6 A) parallel to the c crystallographic axis. To resolve a previously reported discrepancy between nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) data a highly crystalline AlPO4-H2 has been further characterized with 27Al and 31P magic-angle spinning (MAS) NMR at 11.7 T and 27Al double-rotation (DOR) NMR at 4.7 T. These present NMR data definitively show that the true space group symmetry of the AlPO4-H2 framework structure is triclinic rather than the higher orthorhombic symmetry proposed earlier from XRD studies. PMID- 7773651 TI - Solid-state 13C nuclear magnetic resonance spectra of 6-aminopenicillanic acid. PMID- 7773652 TI - Not just the bottom line. PMID- 7773653 TI - Osteonecrosis of the hip in sickle cell hemoglobinopathy. AB - Osteonecrosis secondary to sickle cell anemia and its genetic variants has many presentations depending on the age of onset and the extent of femoral head involvement. Total hip arthroplasty provides the greatest opportunity for clinical improvement of all treatment options, though early and late complication rates are high. Technical difficulties of total hip arthroplasty are related to marrow hyperplasia and the presence of sclerotic intramedullary bone. Surgical complications related to sickle cell hemoglobinopathy include vaso-occlusive crises, congestive heart failure, major transfusion reactions, intraoperative femoral fracture, femoral perforation, late aseptic loosening of acetabular and femoral components, and sepsis. PMID- 7773654 TI - The Peter Principle in orthopedics. AB - Original orthopedic devices that were developed, tested, and found useful, were subsequently modified and seemingly "improved" to a point of diminished usefulness--a manifestation of the Peter Principle applied to orthopedics. The authors describe seven examples: (1) the talar-tilt inversion apparatus; (2) the patellar-tendon-bearing, below-knee amputation prosthesis; (3) the patellar tendon-bearing orthosis; (4) the Veterans Administration Prosthetic Center's lumbosacral orthosis; (5) the partial-foot prosthesis; (6) the ankle-foot orthosis; and (7) the occipito-zygomatic cervical orthosis. PMID- 7773655 TI - Bone marrow/allograft component therapy. A clinical trial. AB - Bone graft is required in clinical orthopedic situations that involve a skeletal defect. Whether the defect is the result of trauma or surgery, autogenous iliac bone graft is the gold standard of therapy. The author used autogenous bone marrow/cancellous allograft as a bone graft substitute in 19 consecutive patients with a bony defect (synthetic bone substitutes were not available commercially when the series began). In this prospective study, both clinical and radiographic outcomes were followed. Of the patients, 100% were clinically healed at the site of grafting; 95% achieved radiographic union. No patients had surgical or postoperative complications. A bone marrow/allograft is a viable alternative to an iliac bone graft. PMID- 7773656 TI - Combined hip surgery in cerebral palsy patients. AB - Seventeen cases of dislocated/subluxated hips in 14 cerebral palsy patients that were relocated by the combined hip procedure were reviewed. The combined hip procedure includes varus derotation osteotomy, open reduction, innominate bone osteotomy, adductor releases, and iliopsoas recession, all done at one stage. Eleven patients were spastic quadriplegic, 1 was spastic diplegic; and 2 were spastic hemiplegic. Average age at operation was 10 years. Average follow-up was 3 years. A total of 16 hips (94%) remained stable at follow-up with almost no change in center edge angle and the migration percentage, although the neck shaft angle remodeled over time. We conclude that the combined hip procedure is effective in maintaining hip reduction in cerebral palsy patients. PMID- 7773657 TI - Chondroblastoma of the patella presenting as knee pain in an adolescent. AB - We report a case of chondroblastoma of the patella, associated with an aneurysmal bone cyst and pathologic fracture, that presented as knee pain in a 13-year-old girl. This case is the fifth case in the literature that associates patellar chondroblastoma with fracture, which should probably be regarded as a significant feature of this lesion. PMID- 7773658 TI - Para-articular osteochondroma. AB - An unusual case of a para-articular osteochondroma in the vicinity of the knee is reported. Typical presentation and differential diagnosis of bone-forming lesions about the knee are discussed. Confirmed diagnosis should combine clinical presentation and appearance, laboratory data, radiographic evaluation, and possible biopsy of the lesion. PMID- 7773659 TI - Avascular necrosis of the medial femoral condyle in HIV-infected patients. AB - Avascular necrosis (AVN) of the femoral head has been described in the literature in patients infected with the human immunodeficiency virus. It has been associated with either a hypertriglyceridemic state or the presence of antiphospholipid antibodies. We describe a case of AVN of the medial femoral condyle in an HIV-infected patient associated with a hypertriglyceridemic state. PMID- 7773660 TI - Tee shirt management of nursemaid's elbow. AB - Subluxation of the radial head, or "nursemaid's elbow," is a common injury among children aged 1 to 4 years. The authors present a technique for flexed-elbow stabilization designed especially for very young children, which provides adequate immobilization without the use of a sling. PMID- 7773661 TI - A 9-year-old girl with swelling and pain in the leg. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopedic surgeon. Initial history, physical findings, and roentgenographic examinations are presented on this page. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 7773662 TI - Mediocrates: father of modern health care. PMID- 7773663 TI - Reflex sympathetic dystrophy. PMID- 7773664 TI - Comparing the efficacy of postoperative pain relief with the use of intra articular morphine versus Marcaine (bupivacaine) following arthroscopy of the knee. PMID- 7773665 TI - The versatility of the gastrocnemius muscle flap. AB - The gastrocnemius muscle rotation flap is a utilitarian procedure for management of soft-tissue defects about the knee. Ten patients underwent medial gastrocnemius muscle rotation flaps at our institution during a 24-month period. Four of the 10 patients underwent primary muscle rotation-plasty for reconstruction following tumor resection; 3 patients had soft-tissue defects following trauma; 2 patients had skin ischemia following total knee arthroplasty; and 1 patient had a soft-tissue defect from scar formation. All procedures were performed by an orthopaedic surgeon. At follow-up of 6 to 24 months, the soft tissue coverage was maintained in all patients. All of the muscle rotation flaps survived. The gastrocnemius rotation flap provides reliable anterior knee soft tissue coverage and can be performed by most orthopaedic surgeons. PMID- 7773666 TI - Scaphoid fractures and nonunions. AB - Fractures of the scaphoid are the most common of all fractures of the carpal bones. Scaphoid collapse and angular deformity may develop after fractures. The tenuous vascular anatomy of the scaphoid, the inherent biomechanical instability of scaphoid fractures, and the difficulty of radiographic diagnosis are the culprits of nonunion. The treatment of established scaphoid nonunion is difficult, and more so is the treatment of failed nonunion after grafting. One common method for treating scaphoid nonunion with angular deformity is length restoration using a wedge bone graft and Herbert screw fixation through a palmar approach. Attention to details of surgical technique are necessary for successful treatment outcome. PMID- 7773667 TI - Conservative options in the management of spinal disorders, Part II. Exercise, education, and manual therapies. AB - At this time, evidence supports exercise as an efficacious form of treatment for individuals suffering from back pain. The incorporation of education regarding posture, body mechanics, and ergonomics as part of a progressive exercise program appears justified. While there is empirical evidence available for the use of biofeedback, there are no specific studies supporting its efficacy in the treatment of the spine. Manual therapies such as mobilization and/or manipulation appear to shorten the course of subacute back pain, but do not alter the natural history and do not appear to be efficacious as monotherapy for chronic back pain. PMID- 7773668 TI - Analysis of the torque applied to bone screws by trauma surgeons. Comparisons based on years of experience and material of implant construction. AB - Stability of an internal fixation construct is dependent on the torque placed on the screws holding the plate, the number of screws in the construct, and the number of cortices purchased by each screw. This study addresses the ability of surgeons to apply uniform torque and the variability between stainless steel and titanium. A total of 630 measurements were made by trained orthopedists using a device to measure the torque applied to 3.5 mm screws when tightening them to a plate. Variations were found to be significant depending on the number of years the orthopedist was in practice and the type of construct material used. The average torque applied to a stainless steel construct is 5.82 in-lb, while the torque applied to titanium is 5.41 in-lb (P < 0.01). The longer an orthopedist is in practice, the more torque will be applied to the screw/plate construct. PMID- 7773669 TI - Assessment of eversion and plantar flexion strength after repair of Achilles tendon rupture using peroneus brevis tendon transfer. AB - Eight patients with Achilles tendon ruptures, one of which was a late discovery, underwent peroneus brevis tendon transfers to repair their injuries. Subsequently, both the repaired and normal extremities of all eight patients were tested for eversion and plantar flexion strength. The Cybex 340 isokinetic system (Lumex Corp, Bayshore, New York) was used at both 30 degrees per second and 120 degrees per second. Patients' affected sides were then assessed subjectively for function compared with their opposite normal sides. Results for eversion strength showed a 17.4% deficit at 30 degrees per second and a 14.9% deficit at 120 degrees per second on the repaired extremity. Only the group with the 14.9% deficit showed a statistically significant difference using the paired t test (P < 0.05). Results for plantar flexion strength showed a 1.5% difference at 30 degrees per second and a 5.8% difference at 120 degrees per second. None of these differences were statistically significant. Subjective assessment showed no functional compromise in eversion strength, plantar flexion strength, activities of daily living, or ankle stability. Conclusions are that mild objective eversion weakness and no objective plantar flexion weakness can be expected after this procedure; however, subjective assessment reveals no functional compromise. PMID- 7773670 TI - A septic hip complicated by a ruptured appendix in an intravenous drug user. AB - This paper reports on a case of hip joint sepsis complicated by a ruptured appendix in an intravenous drug user. A 41-year-old woman underwent open irrigation and debridement of her right hip joint for a methicillin-sensitive Staphylococcus aureus infection. Five days later the patient developed an intraperitoneal mass, requiring laparotomy and debridement of a periappendiceal abscess. The organisms infecting the abscess were different from those infecting the patient's hip. The patient recovered satisfactorily after 6 weeks of intravenous antibiotic therapy. PMID- 7773671 TI - Beware of absent femoral pulse (or how to prevent major complications after minor procedures). AB - The following is presented to illustrate the importance of examining all peripheral pulses, especially the femoral pulse, before performing minor surgical procedures on the lower extremity, even limited toe amputation. This simple examination is a must in identifying patients at risk for severe peripheral arterial insufficiency, which can lead to major complications if underestimated or undiagnosed. We offer three examples to illustrate this point. All patients underwent successful revascularization and major lower limb amputation was avoided. PMID- 7773672 TI - A rare cause of low back pain. AB - An 18-year-old new army recruit had been treated by his medical officer for low back pain. The pain was not relieved by medication, and the soldier was referred to an orthopedic clinic. Muscle power, reflexes, and sensation were all normal for the lumbar and sacral nerves. Roentgenograms revealed a hemivertebra at the level of the first sacral segment. This is a very rare cause of backache in patients with intact and functioning lumbar and sacral nerves. PMID- 7773673 TI - A 55-year-old man with bilateral lower-limb numbness and weakness. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to orthopedic surgeons. The initial history, physical findings, and roentgenographic examinations appear on this page. The clinical and roentgenographic diagnoses are presented on the following pages. PMID- 7773674 TI - Treatment of unstable intertrochanteric hip fractures associated with spinal fractures. A treatment dilemma. AB - Treatment approaches to a patient with polytrauma comprising combined spinal and hip fractures need more careful planning than those for a patient with an isolated spinal or hip fracture. The patient in this case presentation had multiple burst fractures of the spine, but was neurologically intact. The spinal injuries were treated conservatively. The patient also had concomitant unstable intertrochanteric fractures of the hip, which were treated surgically. The presence of a thoracic or lumbar fracture, in addition to a hip or femur fracture, may require an altered therapeutic approach. We present an approach to treating this complex problem without the use of a fracture table. PMID- 7773675 TI - Somatostatin in the prepacemaker nucleus of weakly electric fish, Apteronotus leptorhynchus: evidence for a nonsynaptic function. AB - Neuropeptides are widely distributed throughout the nervous system and exert a large number of heterogeneous functions. While they are synthesized in the soma, release is thought to take place in axonal terminals of neurons. A good model system to investigate the role of peptides in the nervous system is provided by the central posterior/prepacemaker nucleus (CP/PPn) of pacemaker nucleus (Pn), a medullary cell group controlling the electric organ discharge (EOD). Previous immunocytochemical and in situ-hybridization studies employing topographical criteria indicated that PPn neurons may express the neuropeptide somatostatin (SS). In the present study, we unambiguously identified PPn neurons by in vitro tract tracing. By combining this technique with SS immunocytochemistry, we found that a large portion of retrogradely labelled PPn neurons exhibited SS-like immunoreactivity (72-89%, n = 708 cells in 10 fish examined). Surprisingly, however, neither the proximal PPn axons nor anterogradely labelled terminals innervating the Pn displayed significant amounts of SS-like immunolabelling (n = 10 fish examined in each experiment). These results and the lack of SS binding sites in the Pn [82] suggest that SS expressed by PPn cells is not synaptically released at the target site of their axons, the Pn, but acts via a nonsynaptic mechanism in the CP/PPn proper. PMID- 7773676 TI - Effects of in vitro ethanol and chronic ethanol consumption on the release of excitatory amino acids in the rat hippocampus. AB - In CA1-CA3 hippocampal slices, in vitro ethanol (EtOH) (10-100 mM) evoked, as a function of EtOH concentration, a differential release of aspartate (Asp) and glutamate (Glu). Omission of Ca2+ ions from the superfusion media completely abolished the EtOH-induced release of Asp but not that of Glu. In addition, at 20 mM, EtOH enhanced K(+)-evoked release only of Asp. Finally, delayed changes were observed on NMDA-evoked release of [3H]noradrenaline (NA) in the dentate gyrus (DG) after withdrawal from EtOH for 30 days. PMID- 7773677 TI - Evidence that cholera toxin B subunit (CTb) can be avidly taken up and transported by fibers of passage. AB - It has been reported that cholera toxin B subunit (CTb) is a sensitive neuronal tracer with unique features. However, the possible uptake of CTb by non-terminal fibers passing through the injection site has not been examined thoroughly. In the present study, small iontophoretic injections (current = +2 microA) of CTb were made in the olivocerebellar pathway in the rat ventrolateral medulla. A large number of retrogradely labeled neurons were seen in the contralateral inferior olive. In addition, prominent anterogradely labeled climbing fibers/terminals were found in the cerebellum ipsilateral to the injection site. This study, in contrast to previous report(s), indicates that CTb can be taken up avidly by fibers of passage and transported both anterogradely and retrogradely. PMID- 7773678 TI - Regulation of proopiomelanocortin gene expression by neuropeptide Y in the rat arcuate nucleus. AB - In the arcuate nucleus which is richly innervated by both proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons, it has been shown that NPY fibers are in synaptic contact with POMC cell bodies. In order to determine whether NPY could influence POMC neuronal activity, we have studied the effects of NPY and some NPY analogs on POMC gene expression using quantitative in situ hybridization. The following peptides NPY, [Leu31,Pro34]-NPY (a Y1 receptor agonist), and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral cerebral ventricle of adult male rats 4 h before being perfused for histological procedures. The intracerebroventricular injection of NPY and NPY13-36 induced a significant decrease in the number of grains overlying the labelled neurons. On the other hand, the Y1 receptor agonist [Leu31,Pro34]-NPY did not modify POMC mRNA levels. These data then strongly suggest that NPY negatively regulates the genetic expression of POMC neurons via the Y2 NPY receptor subtype. PMID- 7773679 TI - Sulpiride increases and dopamine decreases intracranial temperature in rats when injected in the lateral hypothalamus: an animal model for the neuroleptic malignant syndrome? AB - Sulpiride in the perifornical lateral hypothalamus (pfLH) (4, 8 and 16 micrograms/0.5 microliter) increased intracranial temperature (Tic). The hyperthermia started immediately after the injection, peaked 30 min later and lasted for more than 90 min. Sulpiride (12 micrograms) accelerated recovery from hypothermia in anesthetized animals. Forty-five min after sulpiride Tic raised 1.17 +/- 0.06 degrees C. After a control injection the raise was only 0.5 +/- 0.13 degrees C. Locally applied dopamine (DA) (5, 10 and 20 micrograms) 5 min before sulpiride (12 micrograms) attenuated sulpiride hyperthermia. The largest DA dose reduced Tic (-1.21 degrees C) when administered alone. These findings suggest the existence of D2 receptors in the LH involved in thermoregulation. Changes are that D2 receptors in the human LH could be responsible for the neuroleptic malignant syndrome (NMS), and that sulpiride injections in the rat LH could be used as a model for the study of the pathogenesis of this syndrome. PMID- 7773680 TI - Role of excitatory amino-acids in diethyldithiocarbamate-induced cell death in mesencephalic cultures. AB - The effects of diethyldithiocarbamate (DDC) and DDC plus glutamate on mesencephalic cell cultures were investigated. DDC 10 microM was toxic for cell cultures as assessed by observation under a phase-contrast microscope and the drop in [3H]dopamine uptake. Moreover, DDC 1 microM greatly potentiated cell death induced by glutamate 10 and 50 microM. (+)MK801, a selective non competitive antagonist of NMDA receptors, completely prevented the toxicity of the two neurotoxins. PMID- 7773681 TI - beta-Amyloid peptide decreases membrane fluidity. AB - The beta-amyloid peptide-25-35 (beta A25-35) decreases the fluidity of mouse brain membranes in a concentration-depending fashion. First effects were already seen at a beta A25-35 concentration of 100 nmol/1. beta-Amyloid peptide(1-40) was similarly active. beta A25-35 also decreases the fluidity of human lymphocyte membranes and of membranes from the cortex, hippocampus, striatum, and cerebellum of the rat, although the effects in the rat cerebellum are only weak. Scrambled beta A25-35 when investigated under similar conditions showed no effects on membrane fluidity. It is suggest that the effect on cellular calcium-signalling but also the neurotoxic properties of beta-amyloid might be the result of its concentration depending effects on membrane properties. PMID- 7773682 TI - Intracisternal injection of TRH antibody blocks gastric emptying stimulated by 2 deoxy-D-glucose in rats. AB - We evaluated the effect of 2-deoxy-D-glucose (2-DG) on gastric emptying of a non nutrient solution in conscious rats using a Phenol red method. Intravenous injection of 2-deoxy-D-glucose dose-dependently increased the rate of gastric emptying. This stimulatory action of 2-DG was abolished by subdiaphragmatic vagotomy. Intracisternal injection of thyrotropin-releasing hormone (TRH) antibody blocked intracisternal TRH and intravenous 2-DG-induced enhancement of gastric emptying but not the stimulation of gastric emptying induced by intracisternal pancreatic polypeptide. The TRH antibody injected intraperitoneally had no effect. These results suggest that endogenous TRH in the brain is involved in vagal-dependent stimulation of gastric emptying by 2-DG. PMID- 7773683 TI - Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L carnitine. AB - Treatment of rats with i.c.v. injected streptozotocin (STREP) may provide a relevant model of neurodegeneration that is induced by a decrease in the central metabolism of glucose. Acetyl-L-carnitine (ALCAR) enhances the utilization of alternative energy sources and by such a mechanism of action ALCAR could antagonize the effects of STREP treatment. In this study the effects of chronic treatment with ALCAR were evaluated on spatial discrimination learning in the Morris task and choline acetyltransferase (ChAT) activity of middle-aged STREP treated rats. Chronic treatment with ALCAR attenuated both the STREP-induced impairment in spatial bias and the decrease in hippocampal ChAT activity. These findings indicate that ALCAR treatment has a neuroprotective effect, although further studies are needed to characterize the mechanism of action of ALCAR in this model. PMID- 7773684 TI - Tonotopic organization of responses reflecting stop consonant place of articulation in primary auditory cortex (A1) of the monkey. AB - Current source density and multiunit activity elicited by stop consonant-vowel syllables were examined in primary auditory cortex of an awake monkey. Relative amplitudes of the speech-evoked responses were determined by the onset spectra of the consonants and the tonotopic organization. This finding supports the psychoacoustic hypothesis that the onset spectra of stop consonants are important determinants for the discrimination of place of articulation. PMID- 7773685 TI - Immunocytochemical study with an anti-transferrin binding protein serum: a marker for avian oligodendrocytes. AB - We have investigated immunocytochemically the localization of a transferrin binding protein (TfBP) in adult CNS of avian and mammalian species using a polyclonal antibody raised against the protein purified from hen oviduct membranes (alpha OV-TfBP). TfBP has recently been shown to be HSP108. An overall strong immunoreactivity was revealed in most parts of the avian brains, especially in the white matter. The main immunoreactivity originated in small, intensely reacting cells interpreted as oligodendrocytes. The density of TfBP labeled oligodendrocytes of the avian brains was generally proportional to the degree of myelination. There were no marked differences in TfBP-immunostaining pattern between avian species (chick, pigeon and lovebird). On the other hand, in rat, rabbit and cat brains we could not find any TfBP-immunoreactivity. Immunoelectron microscopy has further revealed that TfBP is present in the light and medium types of oligodendrocytes which are known to have high metabolic activities. TfBP reaction product was homogeneously dispersed throughout the perinuclear cytoplasm and fine processes of oligodendrocytes. The intracytoplasmic organelles such as mitochondria and Golgi apparatus were devoid of reaction product. The presence of TfBP in oligodendrocytes implies that this protein may play an important role in transferrin-mediated iron metabolism in the CNS. The complete lack of cross-reactivity between alpha OV-TfBP and mammalian tissues suggests that there is species variability in TfBP structure. We conclude that this chick TfBP antiserum will prove useful in studies of oligodendrocytes and myelination in the avian CNS. PMID- 7773686 TI - Castration reduces vasopressin receptor binding in the hamster hypothalamus. AB - A recently developed ligand with very high affinity and selectivity for the vasopressin (AVP) V1a receptor subtype (i.e. [125I]Linear AVP antagonist ([125I] LinAntag) was used to describe the distribution of AVP binding sites in the hamster brain, and to determine whether AVP receptor binding was influenced by testicular hormones in sites involved in the regulation of steroid-dependent social behaviors. These studies demonstrated [125I]LinAntag binding in regions of the hamster brain which have not been previously identified with other AVP ligands. In addition, testicular hormones were found to alter [125I]LinAntag binding in two distinct regions, the posterior lateral preoptic-anterior lateral hypothalamic continuum and the posterior ventrolateral hypothalamic nucleus and adjacent tuberal area. PMID- 7773687 TI - High titer antibody to mammalian neuronal sodium channels produces sustained channel block. AB - Antibodies specific for neuronal sodium channels recognized the alpha and beta subunits of the voltage-gated sodium channel on immunoblots of crude rat and cat brain membranes and purified rat brain sodium channels. These antibodies did not recognize channels from rat cardiac or rabbit skeletal muscle. Antibody binding to blots of crude rat brain membranes was blocked by preabsorption of the antibody with purified rat brain sodium channels. Staining of the sodium channel alpha subunit on immunoblots of crude rat brain membranes was easily visualized at antibody dilutions of up to 1:150,000, which is at least 15-fold higher than that reported in previous studies. Addition of antibody produced in one chicken to the extracellular face of batrachotoxin-activated rat brain sodium channels in planar lipid bilayers produced a sustained block of the channel at either hyperpolarized (-65 to -45 mV) or depolarized potentials (+45 to +75 mV). This block was not produced when the antibody was added to the cytoplasmic face of the channel, or if preimmune antibody was added to the extracellular face of rat brain sodium channels. PMID- 7773688 TI - Dynamics of 5-hydroxytryptamine released from dopamine neurons in the caudate putamen of the rat. AB - Fast-scan cyclic voltammetry has been used for the detection of 5 hydroxytryptamine (5-HT) in vivo. The applied potential waveform was previously optimized to maximize response times to concentration changes. This technique has been used to reinvestigate 5-HT release from striatal dopaminergic terminals after pharmacological pretreatment as reported by Stamford et al. [13]. Our results concur with those set forth by Stamford and further show that the dopamine transporter is responsible for 5-HT uptake in this experiment. PMID- 7773689 TI - Right vs. left sensorimotor cortex suction-ablation in the rat: no difference in beam-walking recovery. AB - The ability of rats to traverse a narrow elevated beam has been used to quantitate recovery of hindlimb motor function after unilateral injury to the sensorimotor cortex. We tested the hypothesis that the rate of spontaneous beam walking recovery varies with the side of the cortex lesion. Groups of rats that were trained at the beam-walking task underwent suction-ablation of either the right or left hindlimb sensorimotor cortex. There was no difference in hindlimb motor function between the groups on the first post-operative beam-waking trial carried out the day after cortex ablation and no difference between the groups in overall recovery rates over the next two weeks. Subsequent analyses of lesion surface parameters showed no differences in lesion size or extent. Regardless of the side of the lesion, there were also no differences between the right and left hemispheres in norepinephrine content of the lesioned or contralateral cortex. We conclude that the side of sensorimotor cortex ablation injury does not differentially affect the rate of spontaneous motor recovery as measured with the beam-walking task. PMID- 7773690 TI - Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). AB - Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an analgesic effect. All controls, including a simple mixture of the three components (drugs, nanoparticles, and surfactant) mixed directly before i.v. injection, exhibited no effect. Analgesia was also prevented by pretreatment with naloxone. Fluorescent and electron microscopic studies indicated that the passage of the particle-bound drug occurred by phagocytic uptake of the polysorbate 80 coated nanoparticles by the brain blood vessel endothelial cells. PMID- 7773691 TI - Localization of an isoform of carboxylesterase in rat brain differs from that in human brain. AB - Liver carboxylesterase (CE) is an enzyme capable of metabolizing drugs, and may also function as a regulator of lipid metabolism. We examined two isoforms of CE (RH1 and RL1) by immunohistochemistry in rat brain. The anti-RL1 antibody did not stain any brain structures. The anti-RH1 antibody, however, stained oligodendrocytes in all brain tissues and tanycytes, as well as some neurons in the deep cingulate gyrus, various hypothalamic nuclei and the spinal trigeminal nucleus. In the central nervous system, rat CE may function as a protective factor against foreign chemicals in these glial and neuronal cells. The distribution differed from that of the homologous human isoform which has been previously found only in endothelial cells in human brain. A possible relation between RH1 positive neurons and the medial pain system is discussed. PMID- 7773692 TI - A thermodynamic analysis of estrogen regulation of alpha 2-adrenoceptor binding. AB - We previously demonstrated that in vivo estradiol treatment markedly attenuates alpha 2-adrenoceptor function and coupling to G-proteins in the hypothalamus of female rats. Ligand binding studies indicated that 48 h exposure to estradiol decreases the number of alpha 2-adrenergic receptors in the agonist high affinity state. In the present studies, when [3H]RX821002 was used to label brain alpha 2 adrenoceptors, the density of binding sites significantly increased in the hypothalamus and preoptic area 48 h after estrogen treatment. Moreover, the thermodynamics of ligand binding to alpha 2-adrenergic receptors in membranes of female rat hypothalamus were modified by the same estradiol treatments that reduce alpha 2-adrenoceptor function. In hypothalamic membranes from ovariectomized control rats, antagonist (RX821002)-receptor binding was primarily entropy-driven while agonist (oxymetazoline) binding had a higher enthalpy component. In membranes from estradiol-exposed animals, the entropic contribution to both agonist and antagonist bindings was markedly increased, and the enthalpy component was reduced. Since the thermodynamic characteristics of ligand-receptor binding are strongly correlated with efficacy in activating signal transduction [36], these data raise the intriguing possibility that steroids regulate transmembrane signaling by stabilization of a receptor conformation with reduced intrinsic efficacy. PMID- 7773693 TI - Multisensory convergence and integration in the neostriatum and globus pallidus of the rat. AB - The extracellular response properties of neurons in the caudate-putamen (CPu), globus pallidus (GP) and lateral amygdaloid nucleus (La) evoked by auditory and somatosensory stimuli were investigated. A total of 61 neurons in these areas responded either singly to somatosensory stimulation (unisensory), or to both somatosensory and auditory stimulation (multisensory). Higher rates of somatosensory stimulation reduced the response magnitude of CPu neurons more than that of GP neurons. In multisensory neurons, combined somatosensory and auditory stimulation compared to unisensory stimulation resulted in three characteristic response patterns: enhancement, depression or interaction. Temporal misalignment of the peak frequency latencies evoked by auditory and somatosensory stimulation altered the response magnitude in the majority of neurons. The response properties and anatomical connectivity of CPu and GP neurons suggest that the observed multisensory integrative effects may be used to facilitate motor responses to low intensity stimuli. PMID- 7773694 TI - Plasma hypernatremia induces c-fos activity in medullary catecholaminergic neurons. AB - Experiments were done in conscious rats to investigate the effect of intravenous infusion of hypertonic saline on the induction of the phosphoprotein Fos in brainstem catecholaminergic neurons. Fos induction, detected immunohistochemically, was used as a marker for neuronal activation. Infusions of 165 mM or 1.4 M NaCl solutions into the jugular vein resulted in Fos-like immunoreactivity in approximately the caudal two thirds of nucleus of the solitary tract (NTS), the caudal and rostral ventrolateral medulla (VLM), and in the lateral aspects of the parabrachial nucleus (PBN). Within caudal NTS a small number (7.9 +/- 1.8%) of Fos labelled neurons were found also to contain tyrosine hydroxylase (TH) or dopamine beta-hydroxylase (DBH) immunoreactivity. In rostral NTS no Fos labelled cells were found to contain phenylethanolamine N methyltransferase (PNMT) immunoreactivity, although a few (8.5 +/- 2.3%) were immunoreactive to TH. Similarly, in VLM, most of the Fos labelled cells in caudal VLM (65.9 +/- 2.7%) contained either TH or DBH immunoreactivity, whereas in the rostral VLM, 32.2 +/- 4.6% of the Fos labelled cells were also immunoreactive to TH or DBH. However, no Fos cells were found in either the caudal or rostral VLM that were immunoreactive to PNMT. Little or no Fos-like immunoreactive neurons were detected in the brainstem after intravenous infusions of physiological (143 mM) or hypotonic (106 mM) NaCl solutions. These data suggest that noradrenergic neurons of the caudal NTS and VLM are components of central circuits that are involved in osmoregulation and cardiovascular function. PMID- 7773695 TI - Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. AB - HU-211 is a synthetic, non-psychotropic cannabinoid which acts as a non competitive NMDA antagonist and antioxidant. We studied the drug's therapeutic window as well as its long-term effect on cognitive and motor functions in a model of closed head injury (CHI) in the rat. A weight-drop device was used to induce CHI in either anesthetized male rats. HU-211 (5 mg/kg) was administered i.v. to the experimental groups. For the therapeutic window study, drug was injected at 4 or 6 h after CHI. Edema (water content) and clinical status (neurological severity score, NSS) were evaluated at 24 h. Reduction of edema was slight, whereas improvement of NSS was significant when the drug was administered at 4 or 6 h (P = 0.0023 and 0.059, respectively). To determine the drug's long term effect, it was administered 1 h after CHI and additional doses were later given. NSS was evaluated for a period of 30 d. A single dose of HU-211 given 1 h post-CHI improved the clinical outcome during the 30 d period (P < 0.01). Repetitive doses of HU-211 injected during the post traumatic period had similar effects. Cognitive functions were evaluated in the Morris water maze, with rats trained either before or after CHI. CHI resulted in a highly significant impairment of these abilities, whereas HU-211 treatment 1 h after CHI improved performance. Our results indicate that HU-211 is a potent cerebroprotective agent, with a therapeutic window of about 4 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773696 TI - Chronic administration of (+)-amphetamine alters the reactivity of midbrain dopaminergic neurons to prefrontal cortex stimulation in the rat. AB - Repeated intermittent administration of (+)-amphetamine produces sensitisation to many of the behavioural effects of the drug. Evidence suggests that excitatory amino acidergic projections from the prefrontal cortex (PFC) to dopaminergic (DA) neurons in the ventral midbrain may be partly involved in the maintenance of sensitisation once induced. The present study was designed to investigate whether chronic amphetamine administration produces any alteration to this input, by assessing the impact of single pulse electrical stimulation of the PFC (0.25 and 0.5 mA) on the extracellular activity of individual midbrain DA neurons in drug and vehicle treated rats. Animals were administered amphetamine according to a schedule known to produce sensitisation (2.5 mg/kg free base, once daily for 6 days; s.c.), and the effect of PFC stimulation was assessed on withdrawal days 2 and 10. In addition to single spike firing patterns, the ability of the stimulation to elicit stimulus bound (time-locked) burst events was also noted. In the majority of cases, the elicited responses could be broadly categorised into two types--ones characterised by an initial excitation (E responses) and ones characterised by excitation following an initial inhibition (IE responses). On withdrawal day 2, IE responses were affected such that, in those responses which contained time-locked bursts in their excitatory phases, the stimulus produced a time-locked burst on a greater percentage of trials. On withdrawal day 10, the principal change was that E responses were more likely to occur in amphetamine-treated animals than controls (0.25 mA; 57.1% vs. 41.2% of responses, respectively; 0.5 mA; 36.7% vs. 23.5% of responses, respectively). It is argued that an increase in the proportion of excitatory responses in drug animals indicates a potentiation of the excitatory drive to the DA neurons. Insofar as sensitisation in the longer term relies upon an enhancement of amphetamine induced dopamine release in the forebrain, this may be one mechanism by which it is achieved. PMID- 7773697 TI - Delayed neuronal injury induced by sub-lethal NMDA exposure in the hippocampal slice. AB - Stroke produces neuronal death by two general processes which differ in their temporal course. Acute neuronal death occurs within minutes, while delayed neuronal death evolves within 24 h. To better examine mechanisms of delayed death, we developed a new in vitro model of delayed neuronal injury using extended electrophysiological recordings in paired hippocampal slices. We exposed one hippocampal slice of each pair to 10 microM N-methyl-D-aspartate (NMDA) until the orthodromic CA1 PS disappeared. Thereafter, NMDA-treated slices regained near full recovery of PS amplitude within one hour. However, 10 h later, NMDA-treated slices demonstrated a rapid decline in PS amplitude of 82% +/- 15. CA1 orthodromic evoked PS was lost completely at an average 12.4 +/- 1.6 h after NMDA exposure. This sudden loss of response contrasted with paired, untreated slices, where CA1 PS could be elicited for 22.6 +/- 4.0 h (P < 0.05). Treatment with 10 mM MgCl2 begun after NMDA exposure and continued for 35 min, prevented delayed loss of CA1 orthodromic PS, which then could be elicited for 20.3 +/- 2.1 h. These results indicate that delayed injury can be evaluated using the hippocampal slice. They also suggest that activation of NMDA receptors can induce delayed neuronal injury in CA1 neurons, and that magnesium treatment after NMDA can prevent this injury. PMID- 7773698 TI - Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers. AB - Antibodies to functional AMPA/kainate (GluR1, GluR2, GluR3), and kainate binding sites (GluR5-7) were used as probes to characterize and quantitate glutamatergic receptor subtypes in human post-mortem brain tissue from schizophrenic subjects and non-psychotic control subjects, which included normal controls and subjects with a previous history of alcohol abuse. Crude membrane fractions from human hippocampi and cingulate cortices were fractionated by SDS-PAGE, electrotransferred to nitrocellulose, and probed for the various glutamate receptor subtypes. Western blots were developed with chemiluminescence and the images analyzed by densitometry. Significant reductions were observed in the hippocampal immunoreactivity of both GluR2 and GluR3 AMPA/kainate receptor subtypes in schizophrenic subjects compared to the entire group of non-psychotic control subjects. No significant changes were observed in schizophrenic hippocampal GluR1 and GluR5 receptor subtypes or in levels of the structural control proteins, NCAM and tau. Significant increases were observed for GluR2 and GluR3 in the hippocampi of subjects with alcohol abuse histories when compared to the non-psychotic normal control group. When subjects with alcohol abuse histories were removed from the non-psychotic control pool, schizophrenics were no longer statistically different from the remaining normal controls. An analysis of GluR2 and GluR3 immunoreactivity in the cingulate cortex revealed no changes in these receptor subtypes among any of the groups. No alterations were observed in the immunoreactivity of these various proteins due to confounding factors such as age, sex, postmortem interval, or smoking history, except in the cingulate cortex were GluR3 receptor subtype levels were significantly reduced in the brains of smokers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773699 TI - Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study. AB - Intrahippocampal injections of N-methyl-D-aspartic acid (NMDA) leads to neurodegeneration in a dose-dependent manner. Chronic administration of ethanol to animals leads to CNS tolerance and dependence. Hyperexcitability following ethanol withdrawal is thought to be related to increased sensitivity of the NMDA receptors. The purpose of this study was to investigate this predisposition to hyperexcitability by intrahippocampal injection of low dose of NMDA. Using control and ethanol-withdrawn male Wistar rats, behavioural indices were determined immediately after injection and morphological damage was assessed after a period of recovery. There was significantly increased hyperactivity in the ethanol-treated rats immediately after injection. Morphological damage resulting from 5 nmol of NMDA was significantly greater in the CA3 region of the hippocampus in these animals. These data support the hypothesis that ethanol dependence and subsequent withdrawal is associated with increased sensitivity to NMDA which may underlie ethanol withdrawal-associated brain damage. PMID- 7773700 TI - Staff perception of their roles during the transition of psychiatric care into the community. AB - The objective of this study was to investigate the staff's experiences involved in the processes of the transition of 20 non-demented long-stay psychiatric patients. Staff members expressed satisfaction from working outside the hospital. They believed that the patients' condition and their quality of life had improved and that they were likely to achieve successful resettlement after a lengthy process of rehabilitation. However, staff members considered that their roles were demanding and involved a lot of domestic activities. They recommended gradual and slow preparation for the patients, and an educational programme for the public as well as appropriate preparation and continuing professional support for staff. PMID- 7773701 TI - Formulation and testing of a nursing assessment form for mental patients as a basis for individualized nursing care. AB - The study described here was designed to develop and test a form of nursing assessment of mental patients for use as a basis for individualized holistic nursing care in any setting. Nursing assessment was made of 581 mental patients receiving care in either mental hospitals, psychiatric departments of general hospitals or in mental health centres. Subjects were observed, interviewed and asked to complete a structured assessment form. Major variables studied were physical nursing problems/needs with nine categories, psychosocial nursing problems/needs with nine categories, sex, age, and physical and psychiatric disorders. Data were analysed with frequency distribution and comparative techniques, correlational procedures, and the multiple linear regression statistical procedure. The frequency distribution of psychiatric diagnoses showed that schizophrenic disorders were the most frequent in the total sample. However, there were more depressive patients in the general hospital group. Physical nursing problems/needs were significantly related with psychosocial nursing problems/needs, affective-depressive disorders, sex and age as well as negatively related with psychotic and anxiety disorders. Psychosocial nursing problems/needs were significantly related with schizophrenic and psychotic disorders, physical disorders and with the younger age groups. It was concluded that the psychiatric nursing assessment should encompass the areas of personal characteristics, and physical and psychological problems of the patient, and thus lead to practicing psychiatric nursing, that is, holistic psychosomatic nursing. PMID- 7773702 TI - Evaluation of a transitional residential programme for homeless chronically mentally ill people. AB - This paper reports a successful transitional programme in the USA. The research programme evaluation covered 5.5 years and 228 severely and persistently mentally ill homeless clients who lived in a transitional residential centre. Forty-eight per cent of the residents achieved the Programme's goals of obtaining and maintaining permanent housing and a disability pension or a job. Achievement of client goals was positively related to length of stay of 3 months or more, to five or more previous psychiatric hospitalizations, and to participation in two or more ongoing activities whilst in the programme. Psychiatric diagnosis was not directly related to goal attainment in this programme. PMID- 7773703 TI - A stitch in time. Facilitating proactive interventions with dementia caregivers: the role of community practitioners. AB - The role of family caregivers in supporting people with dementia in the community is beyond question. Yet, all too often, the needs of such carers are overlooked by community practitioners. This paper describes the results of a study in Wales examining the experiences of dementia caregivers with Community Practitioners. Four themes are identified which encapsulate the various difficulties carers faced. These revolve around a lack of communication, information and support. Recommentations to improve the current situation are made. PMID- 7773704 TI - Mental health nursing: a global perspective. AB - This paper is based on a presentation by Dr Oguisso to the First Hamburg World Forum on Mental Health, 11 June 1994, for the Standing Committee of Presidents of International Non-Governmental Organizations Concerned with Mental Health Issues. Over recent years, the International Council of Nurses (ICN) has been concerned that health providers are sometimes not adequately prepared to give quality care and that resources are often well below those targeted for other sectors of the health care system. In 1991 the ICN chose 'Mental Health--Nurses in Action' as the theme for International Nurses Day on 12 May. With the help of the ICN provided educational kits, national nurses' associations updated nurses on the problems and informed the public that nurses as a group can provide many of the mental health services to people and answer their families needs. PMID- 7773705 TI - A study of the relationship between student nurses' and role models' empathy levels. PMID- 7773706 TI - Controlled comparison of three interventions with parents of children with learning disabilities exhibiting challenging behaviours. PMID- 7773707 TI - Development of a drop-in service in a small community team: continuing care to clients with long-term mental health problems. PMID- 7773708 TI - Survivor blaming. PMID- 7773710 TI - The Isle of Wight: emergency care during Cowes Week. PMID- 7773709 TI - Stress and the community mental health nurse: the development of a measure. AB - The issue of stress amongst health care professionals is currently a major concern within the British National Health Service. It is important for researchers to develop both reliable and valid psychometric measures to assess occupational stress. This paper outlines the development and piloting of a measure of professional stress for community mental health nurses, the CPN Stress Questionnaire (Revised). Data on the reliability and validity of this new measure are presented. It is concluded that this measure has good psychometric properties. A range of possible research applications is outlined. PMID- 7773711 TI - The health repercussions of government transport policies. PMID- 7773712 TI - The scope of professional practice and the accident and emergency nurse. PMID- 7773713 TI - Specialist units. PMID- 7773714 TI - Should relatives be present in the resuscitation room? AB - Many Accident & Emergency (A & E) nurses will be familiar with the situation of resuscitating an individual who may be, for example, a husband, father or son. When the severity of illness gives rise to question the probability of continuing life, what about the relatives - those people who hold most importance to that individual? The relatives are sometimes unaware of the sudden illness and can be left isolated in the realisation that their loved one has died, and they were not there. How often are relatives there when an individual dies suddenly in the A & E department? These emotive factors led to this discussion and study of the attitudes of hospital and ambulance staff towards permitting relatives to be present during a resuscitation. PMID- 7773715 TI - Use of video recorders in auditing initial assessment times. AB - The Patient's Charter (Department of Health 1992) states that patients attending Accident and Emergency departments will 'be seen immediately' and have 'their need for treatment assessed'. This paper describes a research project aimed at gathering accurate and reliable information regarding initial assessment times in a busy Emergency department. The use of closed circuit cameras and video recordings will be described. Ethical considerations will be highlighted along with the results of the study. PMID- 7773716 TI - Minor Injuries Unit: expanding the scope of accident and emergency provision. AB - The Minor Injuries Unit at St Charles Hospital, London, opened in early 1993. Its establishment is placed in the context of radical changes occurring in Accident and Emergency provision within the UK. The unit's success has exceeded initial expectations and mirrors the potential for such units detailed in recent studies. The use of treatment and prescription protocols are discussed. The effective utilisation of existing and potential nursing skills is demonstrated. PMID- 7773717 TI - Miscarriage counselling--an accident and emergency perspective. AB - Many women attend the Accident and Emergency department with vaginal bleeding as the first signs of a possible miscarriage. This study was undertaken to identify the views of Accident and Emergency nurses with regard to counselling these women in the Accident and Emergency department, and who should be undertaking the counselling. 50 questionnaires were distributed to 10 Accident and Emergency departments within the Yorkshire region, to qualified nurses of various grades and experience. 50% of the respondents said that counselling should be undertaken during the couple's stay in the department. This paper discusses where and when counselling should be undertaken, by whom and also focuses on the feelings, thoughts and needs of the couple. PMID- 7773718 TI - Violence in the accident and emergency department. AB - A survey of Accident and Emergency nurses was undertaken to study the prevalence, types and possible precipitating factors of violence in the workplace. Violence was sub-divided into physical and verbal. Verbal violence was more common than physical assault but often not reported. Often physical violence is under reported but in fact had affected one third of respondents. Associations with different types of violence are discussed. The need for further training in defusing violent situations and analysis of violent incidents is identified. Some suggestions for inclusion in a training programme are given. PMID- 7773719 TI - Children's experiences of pain in an accident and emergency department. AB - Controlling pain in sick or injured children continues to be a challenge, particularly for those working in Accident and Emergency departments. Empathising with the subjectivity of a child's experience, provides insight into the range of significant events that frequently exacerbate the quality and intensity of physical pain; the latter being compounded by the 'emotion' pain of fear, misunderstanding, separation or distress. This article stresses the importance of an holistic approach for effective pain management. The developmental aspects of the perceptual, interpretative and expressive components of pain will be explored and a range of pain assessment tools considered. PMID- 7773720 TI - HIV in the accident and emergency department. AB - This article is intended as an introduction to some of the issues which arise from the increasing incidence in the UK of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). It is not possible fully to address, nor offer answers to, all of these issues. HIV and AIDS present many challenges to nurses. It tests not only our skills and methods of practice, but confronts our feelings about people whose lifestyles and behaviours may be different from our own (Lert & Marne 1992; McGrath et al 1993); it has also prompted us to alter our awareness and knowledge of medical, nursing and infection control issues. Hopefully this article will serve to stimulate reflection, thought and discussion as well as generating further, more specific papers of relevance to the Accident and Emergency nurse. PMID- 7773721 TI - Children in accident and emergency: parental perceptions of the quality of care. Part 2. PMID- 7773722 TI - Research based training for the nurse practitioner. AB - Exploration for oil and gas began in the North Sea in the mid 1960s. Since that time offshore medics have had the authority to diagnose and treat patients within a set of guidelines. As such they are one of the earliest groups of British nurse practitioners. Training for offshore medics in the UK sector of the North Sea is regulated by the Health and Safety Commission. In order to promote training based on research, a study was conducted to examine the pattern of referrals to the Accident and Emergency department of Aberdeen Royal Infirmary from offshore. This was done for a 9 year period. The purpose was to establish a reliable database of the most frequently occurring injury types and affected body parts, and to use this information to modify existing training courses for offshore medics. The total number of injury referrals during the study was 6270. The most common injury type was fracture/suspected fracture (mean = 50% +/- 3.2%) and the most common body part affected was the hand (mean = 37% +/- 3.7%). This paper indicates the changes which were made to an offshore medic training programme as a result of the research. It is suggested that unless such research is undertaken it is not possible to claim that the training of nurse practitioners, in this case offshore medics, is research based and therefore relevant to the needs of the community being served. PMID- 7773723 TI - Conflicts of practice confronting second line nurse managers in an accident and emergency department. Part I. AB - In recent times in Australia, there has been a proliferation of nursing career structures which aim to address the historical neglect of a career path for clinical nurses. Among these developments has been the formulation of a new and exciting nursing role, that of the second line nurse manager. This role was designed to give experienced nurses who traditionally worked 'in charge' formal recognition of their knowledge and skill, and sought to construct a role that encompassed both clinical and managerial responsibilities. However, the reality of these nurses' practice is fraught with problems and difficulties as they attempt to negotiate a new and uncharted domain. This paper recounts an action research study conducted by a group of second line nurse managers in an Accident and Emergency department, who sought to explore the dimensions of their practice. The study identifies problems with combining clinical and managerial responsibilities in the one role, within a context marked by a high level of unpredictability, and a culture which values clinical practice over other forms of nursing practice. The paper concludes with a number of recommendations to overcome these problems. PMID- 7773724 TI - Myocardial infarction and cardiovascular risk factors in Mexico City and San Antonio, Texas. AB - Because the epidemiology of cardiovascular disease in Mexico is largely unknown, we examined the prevalence of cardiovascular risk factors and myocardial infarction (MI) in adults from low-income colonias in Mexico City. Data were collected as part of the Mexico City Diabetes Study, a population-based survey of diabetes and cardiovascular disease conducted between 1987 and 1992. Results were compared with those obtained from a comparable survey conducted previously among low-income Mexican Americans in San Antonio, Tex. A total of 2271 individuals between the ages of 35 and 64 years from Mexico City and 1143 adults of the same age range from San Antonio were studied. Despite being leaner and having lower levels of total cholesterol, Mexicans in Mexico City had markedly higher levels of triglycerides (P < .001) and lower levels of HDL cholesterol (P < .001) than Mexican Americans in San Antonio. MI was assessed by Minnesota-coded electrocardiograms and by a self-reported history of physician-diagnosed heart attack. In men, the prevalence of self-reported heart attack was significantly higher in San Antonio than in Mexico City (odds ratio, 5.85; P < .001), and in women, the prevalence of electrocardiogram-documented MI was significantly higher in San Antonio than Mexico City (odds ratio, 2.51; P < .001). The apparent excess of MI in San Antonio relative to Mexico City could be due to higher case-fatality in Mexico City or to a higher incidence in San Antonio. PMID- 7773725 TI - Association between beta-carotene and acute myocardial infarction depends on polyunsaturated fatty acid status. The EURAMIC Study. European Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast. AB - Because antioxidants may play a role in the prevention of coronary heart disease by inhibiting the peroxidation of polyunsaturated fatty acids (PUFAs), the combined association of diet-derived antioxidants and PUFAs with acute myocardial infarction (MI) was investigated. This multicenter case-control study included 674 patients and 725 control subjects in eight European countries and Israel. Fatty acid composition and alpha-tocopherol and beta-carotene levels were determined in adipose tissue; selenium level was determined in toenails. For alpha-tocopherol no association with MI was observed at any PUFA level. The overall multivariate odds ratio (OR) for low (10th percentile) versus high (90th percentile) beta-carotene was 1.98 (95% confidence interval [CI], 1.39 to 2.82). The strength of this inverse association with MI was dependent on PUFA levels (in tertiles): for low PUFA, the OR for low versus high beta-carotene was 1.79 (95% CI, 0.98 to 3.25), for medium PUFA the OR was 1.76 (95% CI, 1.00 to 3.11), and for high PUFA 3.47 (95% CI, 1.93 to 6.24). For selenium increased risk was observed only at the lowest PUFA tertile (OR, 2.49; 95% CI, 1.22 to 5.09). This interaction between selenium and PUFAs was not significant and may at least partly be explained by a higher proportion of smokers at the low PUFA level. These findings support the hypothesis that beta-carotene plays a role in the protection of PUFAs against oxidation and subsequently in the protection against MI. No evidence was found that alpha-tocopherol or selenium may protect against MI at any level of PUFA intake. PMID- 7773726 TI - Oxidation-related analytes and lipid and lipoprotein concentrations in healthy subjects. AB - The relations between oxidation-related analytes and lipoprotein risk factors for coronary heart disease are poorly understood. To address this issue, ceruloplasmin, copper, iron, ferritin, cotinine, lipid peroxides, cholesterol, triglyceride, apoB, apoA-I, and lipoprotein(a) levels were measured in sera from apparently healthy subjects (51 men and 115 women). Pairwise comparisons revealed strong positive associations (P < .001) of copper and ceruloplasmin with lipid peroxides, total cholesterol, triglycerides and apoB, of transferrin with apoA-I and cholesterol, and of ferritin with triglycerides. Serum levels of oxidation related analytes did not differ between smokers and nonsmokers. In multivariate analysis, serum copper was the major independent determinant of serum lipid peroxide level, accounting for 15% of the variability in concentration (ferritin accounted for 1.6%). Copper and ceruloplasmin accounted for 20.5% of the variation in triglyceride levels; triglycerides and apoB accounted for 12% of the variability in ferritin levels; apoB and apoA-I accounted for 9% of the variability in transferrin levels. The data suggest that serum copper contributes to lipid peroxidation in vivo. There are significant associations between lipoprotein and transition metal-related analytes, and further work is needed to elucidate the physiological basis for these relations. PMID- 7773727 TI - Inhibition of the oxidative modification of LDL by nitecapone. AB - We studied in vitro the ability of nitecapone, 3-[(3,4-dihydroxy-5 nitrophenyl)methylene]-2,4-pentanedione, a novel water-soluble compound with antioxidative properties, to inhibit the LDL oxidation promoted by copper ions, the aqueous free radical generator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), and mouse peritoneal macrophages. In these three oxidation systems, the extent of LDL oxidation was determined by measuring the formation of conjugated dienes, the formation of thiobarbituric acid-reactive substances, the change in the electrophoretic mobility of LDL, and the uptake of LDL by macrophages. When LDL oxidation was promoted by copper ions, the reaction was found to be inhibited by nitecapone added in a three- to five-molar excess of the concentration of copper ions. The mechanism by which nitecapone exerted its antioxidative effect in copper-mediated LDL oxidation depended on binding and redox inactivation of the copper ions. Moreover, nitecapone released LDL-bound copper ions and so rendered the LDL particles more resistant to oxidation. In contrast to a water soluble alpha-tocopherol analogue that was rapidly consumed during the oxidative process, nitecapone retained its inhibitory effect for at least 2 days. Using immobilized metal ion affinity chromatography, we showed that nitecapone binds both copper and iron ions, whereas its affinity for zinc ions is low. Nitecapone also inhibited LDL oxidation in the free radical-mediated oxidation system (AAPH). In this system, nitecapone showed synergistic antioxidative action with ascorbic acid. Finally, nitecapone inhibited macrophage-mediated LDL oxidation. Accordingly, nitecapone appears to have a unique antioxidative profile in that it both selectively chelates pro-oxidative transition metals and scavenges free radicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773728 TI - Whole-blood platelet aggregation predicts in vitro and in vivo primary hemostatic function in the elderly. AB - Increased platelet aggregation is associated with higher coronary artery disease mortality. Enhanced platelet aggregation in platelet-rich plasma has also been described in the elderly. To define age-related changes in primary hemostasis, we studied 37 elderly and 31 young blood donors. There were no significant age related differences in whole-blood platelet aggregation, platelet adherence and thrombus formation on human umbilical artery segments, or bleeding time. Plasma fibrinogen was significantly higher in elderly men and women, whereas activated factor VII was elevated only in elderly women. Collagen-induced platelet aggregation was significantly correlated with platelet adherence to the subendothelium in elderly (r = .488, P = .002) but not in young donors. Accordingly, collagen-induced platelet aggregation showed a significant inverse correlation with bleeding time only in the elderly (r = -.401, P = .014). Arachidonic acid-induced platelet aggregation was significantly associated with platelet adherence to the subendothelium (r = .658, P = .003) and bleeding time (r = -.540, P = .021) only in elderly men. In young donors, ADP-induced platelet aggregation was significantly correlated with platelet adherence to the thrombogenic adventitial surface (r = .395, P = .031); in the elderly this association only approached significance (r = .315, P = .058). Whole-blood platelet aggregation in response to collagen and arachidonic acid may be more useful in predicting primary hemostatic function in the elderly than in the young. Furthermore, in the elderly, the correlation between platelet aggregation in whole blood and platelet-arterial wall interactions in vitro and in vivo may contribute to the ability of this test to predict coronary risk. PMID- 7773729 TI - Evidence that meizothrombin is an intermediate product in the clotting of whole blood. AB - Meizothrombin is an intermediate that is produced during the conversion of prothrombin to thrombin in systems composed of purified factor Xa and factor Va that are quantitatively assembled on an anionic phospholipid surface. The biological significance of this intermediate has recently been challenged by the apparent absence of meizothrombin during clotting of sodium citrate anticoagulated plasma. We analyzed the formation of thrombin during coagulation of nonanticoagulated, unchilled, minimally manipulated whole blood in glass tubes. The process was stopped at 0, 3, 5, and 7 minutes by the addition of biotinylated peptidyl chloromethyl-ketone active-site labeling reagents. Plasma/serum was separated by centrifugation, and labeled species were extracted by immunoadsorption with a polyclonal anti-prothrombin antibody. The purified prothrombin-derived species were separated by SDS-polyacrylamide gradient gel electrophoresis and visualized on a chemiluminescent avidin blot. Meizothrombin appeared as an intermediate product of this reaction and persisted with some increase through the 7-minute time point. We also observed incorporation of the active-site label into a species of lower molecular weight consistent with the B1 chain of beta- and/or gamma-thrombin. These degraded forms of thrombin have not been previously demonstrated in a biologically relevant preparation. Our data clearly establish the generation of meizothrombin as an intermediate product of thrombin generation during whole-blood clotting. The data also represent the first experimental evidence for the generation of beta- and gamma-thrombin in a biologically relevant environment and time scale. PMID- 7773730 TI - Platelet cytosolic Ca2+ and membrane dynamics in patients with primary hypercholesterolemia. Effects of pravastatin. AB - This study was designed to evaluate the relationships between platelet cytosolic Ca2+ concentration ([Ca2+]i) and plasma lipids in patients with primary hypercholesterolemia. In a double-blind, placebo-controlled trial, we determined platelet [Ca2+]i in the presence and virtual absence of extracellular Ca2+ and the effects of prolonged treatment with pravastatin, a selective inhibitor of 3 hydroxy-3-methylglutaryl coenzyme A reductase. Platelet [Ca2+]i and membrane microviscosity were determined in 22 normotensive hypercholesterolemic men. Platelet [Ca2+]i was observed to vary with in vivo plasma lipid characteristics: in untreated patients, [Ca2+]i determined at low extracellular Ca2+ concentration was significantly associated with plasma triacylglycerols (P = .008) and with the total cholesterol to HDL cholesterol ratio (P = .044). Triacylglycerol levels also correlated inversely with the external Ca(2+)-dependent [Ca2+]i rise. Pravastatin treatment reduced plasma total cholesterol (-20 +/- 3%), LDL cholesterol (-30 +/- 3%), triacylglycerols (-17 +/- 6%), and apoB levels (-25 +/- 4%) and simultaneously decreased platelet [Ca2+]i measured in a low-Ca2+ medium by 14 +/- 6% (P = .03). However, [Ca2+]i values remained positively correlated with the total cholesterol to HDL cholesterol ratio (P = .04). Prvastatin treatment did not induce marked changes in membrane microviscosity, although the changes in trimethylaminodiphenylhexatriene anisotropy were inversely correlated with those of HDL cholesterol. These results indicate that plasma lipids can modulate cytosolic Ca2+ in platelets by affecting Ca2+ transport pathways that are dependent and independent of Ca2+ influx. PMID- 7773731 TI - FH Afrikaner-3 LDL receptor mutation results in defective LDL receptors and causes a mild form of familial hypercholesterolemia. AB - Three founder-related gene mutations (FH Afrikaner-1, -2, and -3) that affect the LDL receptor are responsible for 90% of the familial hypercholesterolemia (FH) in South African Afrikaners. Patients heterozygous for the FH Afrikaner-1 (FH1) mutation, which results in receptors having approximately 20% of normal receptor activity, have significantly lower plasma cholesterol levels and milder clinical symptoms than heterozygotes with the FH Afrikaner-2 mutation, which completely abolishes LDL receptor activity. In this study we re-created the FH3 mutation (Asp154-->Asn) in exon 4 by site-directed mutagenesis and analyzed the expression of the mutant receptors in Chinese hamster ovary cells. The mutation resulted in the formation of LDL receptors that are markedly defective in their ability to bind LDL, whereas binding of apoE-containing beta-VLDL is less affected. The mutant receptors are poorly expressed on the cell surface as a result of significant degradation of receptor precursors. The plasma cholesterol levels of 31 FH3 heterozygotes were similar to FH1 heterozygotes but significantly lower than FH2 heterozygotes. The FH1 and FH3 heterozygotes also tended to be less severely affected clinically (by coronary heart disease and xanthomata) than FH2 patients. This study demonstrates that mutational heterogeneity in the LDL receptor gene influences the phenotypic expression of heterozygous FH and that severity of expression correlates with the activity of the LDL receptor measured in vitro. The results further indicate that knowledge of the specific mutation underlying FH in heterozygotes is valuable in determining the potential risk of premature atherosclerosis and should influence the clinical management of FH patients. PMID- 7773732 TI - A novel variant of lysosomal acid lipase (Leu336-->Pro) associated with acid lipase deficiency and cholesterol ester storage disease. AB - Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G-->A mutation at the 3' splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T-->C transition in exon 10 predicting a Leu336-->Pro (L336P) replacement and an A-->C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in cis with the mutation predicting the T-6P-encoding allele but in trans with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T 6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD. PMID- 7773733 TI - Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia. AB - Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. The present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk factors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance and 57 with noninsulin-dependent-diabetes mellitus (NIDDM), and compared various aspects of glucose, insulin, and lipoprotein metabolism in the three ACE genotypes. In general, normal subjects with the DD genotype had a lower body mass index, were more insulin sensitive (as assessed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride and cholesterol concentrations were lowest and HDL cholesterol concentrations highest in the DD group. However, the only statistically significant differences were between the ID and DD groups; the latter had lower values for body mass index, was more insulin sensitive, and had a lower plasma insulin response to oral glucose. Similar but insignificant trends were noted in the patients with NIDDM. The present results show that subjects with the ACE/DD genotype are not at increased risk for CHD because of insulin resistance, relative hyperglycemia and hyperinsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773734 TI - Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. AB - To determine the prevalence of the factor V Leiden gene mutation in relation to the phenotypes of cerebral infarction and cerebral hemorrhage, we studied 386 randomly selected cases of acute stroke and 247 control subjects. Factor V genotype was determined by amplification of a 267-bp sequence of exon/intron 10 of the factor V gene. Levels of prothrombin fragment F(1 + 2), a marker of thrombin generation, were determined in both acute and convalescent stroke and related to factor V genotype. Prothrombin fragment F(1 + 2) was assessed by using an enzyme-linked immunosorbent assay. Sixteen stroke cases (4.1%) were identified as having the mutation compared with 14 (5.6%) control subjects. Prothrombin fragment F(1 + 2) levels were estimated in 191 cases and found to be elevated both acutely and after 3 months, but they were not related to factor V genotype. Prothrombin fragment F(1 + 2) is elevated in acute stroke and requires further evaluation in relation to cerebrovascular disease. These results suggest that the factor V Leiden gene mutation is not a risk factor for arterial thrombosis causing stroke. PMID- 7773735 TI - Adsorption and coagulability of fibrinogen on atheromatous lipid surfaces. AB - Fibrinogen, the precursor of the blood clot matrix and a major constituent of atherosclerotic lesions, is shown to adsorb with high affinity to hydrophobic beads coated with cholesteryl oleate, cholesterol, or loosely packed lecithin. The quantity of fibrinogen that binds to cholesterol- or lecithin-coated beads decreases as the surface concentration of the lipid increases; densely packed films lecithin bind little,if any, if the protein. In sharp contrast, the appreciable quantity of fibrinogen that binds to cholesteryl oleate-coated beads is indifferent to the surface concentration of that lipid. Not unexpectedly, the quantity of fibrinogen that binds to beads coated with mixtures of cholesteryl oleate and lecithin increases with increasing concentration of the cholesteryl ester. When bound, fibrinogen can be converted by thrombin to fibrin and nucleate clot formation as manifested by the aggregation of stirred beads. These results indicate that hydrophobic, atheromatous lipid surfaces, particularly those rich in cholesteryl esters, may be predisposed to thrombosis by virtue of their inherent capacity to bind functional fibrinogen. PMID- 7773736 TI - Thrombotic thrombocytopenia induced in dogs and pigs. The role of plasma and platelet vWF in animal models of thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenia with severe depletion of plasma von Willebrand factor (vWF) was induced in normal large animals (5 dogs and 2 pigs) by botrocetin, a Bothrops factor requiring vWF for platelet agglutination. Botrocetin (90 to 100 U/kg, 2.14 to 2.38 mg/kg, in a single i.v. injection) reduced plasma vWF activity to < 0.1 U/mL for 24 hours. During this period, multimeric analysis of plasma vWF antigen (Ag) revealed the loss of intermediate- and high-molecular-weight forms with a concomitant increase in lower molecular weight forms. A moderate reduction in factor VIII (FVIII) activity was observed. The vWF reduction was accompanied by transient thrombocytopenia and prolonged bleeding times during the deficiency state. Occlusive platelet thrombi were detected by transmission electron microscopy in the microcirculation of lung and spleen but not kidney or brain 30 minutes after the botrocetin injection. Recovery of plasma vWF and platelet count occurred within 48 hours and was associated with the appearance in the plasma of unusually large forms of vWF:Ag multimers. The vWF:Ag multimer distribution was normal at 72 hours. The ultrastructural distribution of vWF in unstimulated normal porcine and canine platelets was examined by using immunogold staining. VWF was detected in the alpha-granules of normal pig platelets but was not observed in platelets from normal dogs. However, both animals developed thrombotic thrombocytopenia when injected with botrocetin. A second group of animals (2 dogs and 3 pigs) with von Willebrand disease (vWD) was given a single botrocetin injection (90 to 100 U/kg). No thrombocytopenia occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773737 TI - Mast cell granule remnants carry LDL into smooth muscle cells of the synthetic phenotype and induce their conversion into foam cells. AB - We report the effect of mast cells on the uptake of LDL by smooth muscle cells (SMCs) and their conversion into foam cells in vitro. The mast cells were stimulated to exocytose their cytoplasmic secretory granules, and the granule remnants formed were recovered from the extracellular fluid and added to cultures of SMCs of either the synthetic or contractile phenotype in LDL-containing medium. In the presence but not in the absence of granule remnants, SMCs of the synthetic phenotype took up LDL with ensuing stimulation of intracellular cholesteryl ester synthesis and cytoplasmic accumulation of neutral lipid droplets. Using methylated LDL (mLDL), a modified species of LDL that binds to granule remnants but not to LDL receptors, we demonstrated that this uptake (leading to foam cell formation) occurred only when LDL was bound to granule remnants. After the addition of colloidal gold-LDL and granule remnants to the incubation system, electron microscopy revealed that within phagosomes of the SMCs there were granule remnants (diameter, 0.5 to 1 micron) coated with LDL, confirming that LDL had been carried into the cells with the remnants. SMCs of the contractile phenotype were less efficient than their synthetic counterparts at phagocytosing LDL-coated granule remnants and were not converted into foam cells. This difference in the rate of phagocytosis of granule remnants was present even in the absence of LDL, revealing that the more active phagocytosis by SMCs of the synthetic phenotype was not specifically related to uptake of lipids but rather reflected a general phenotype characteristic of these cells. These observations indicate a phagocytic mechanism by which SMCs of the synthetic phenotype are converted into cholesteryl ester-filled foam cells, and they also suggest that degranulation of mast cells plays a role in the development of fatty streak lesions. PMID- 7773738 TI - IgE-dependent generation of foam cells: an immune mechanism involving degranulation of sensitized mast cells with resultant uptake of LDL by macrophages. AB - Because a role has been suggested for IgE in cardiovascular diseases and for mast cells in cholesterol accumulation within the macrophages of atherosclerotic lesions, we examined mast cell-macrophage interactions in vitro by using rats with high serum levels of IgE antibodies. The rats were immunized with an antigen (ovalbumin) and adjuvant (Bordetella pertussis vaccine) to provoke synthesis of IgE and to sensitize their mast cells, ie, to allow the IgE to bind to the high affinity IgE receptors on the mast cell surfaces. On addition of the ovalbumin to suspensions of mast cells isolated from the peritoneal cavity of the immunized rats, the mast cells responded by exocytosing their heparin-proteoglycan- containing granules. When IgE-bearing peritoneal mast cells were cocultured with peritoneal macrophages (also from the immunized rats) in a medium enriched in LDL, addition of ovalbumin to the incubation medium triggered a dose-dependent release of granules and a dose-dependent increase in the rate of LDL uptake by the macrophages. In contrast, ovalbumin had no effect on LDL uptake if the cultures contained only macrophages or if the mast cells and macrophages were from nonimmunized rats. Thus, the sequence of events leading to enhanced uptake of LDL by macrophages depended wholly on IgE-dependent degranulation of the sensitized mast cells. With the aid of gold-labeled LDL we demonstrated that the exocytosed mast cell granules had bound LDL particles and carried them into the macrophages, with subsequent formation of foam cells. The current series of experiments delineates a novel immunologic mechanism for the formation of macrophage foam cells and assigns a potentially atherogenic role to mast cell bound IgE antibodies. PMID- 7773739 TI - Protein-peptide interactions. AB - Proteins can interact with short peptide sequences in a variety of ways that can be sequence dependent or independent. The bound peptides are frequently in an extended conformation but may also adopt beta-turns or alpha-helices as motifs for recognition. The peptides can be completely buried in cavities, bound in grooves or pockets, or form beta-strand type interactions at the protein surface. These various recognition motifs are illustrated by peptide interactions with antibodies, calmodulin, OppA periplasmic binding protein, PapD chaperone, MHC class I and class II molecules, and Src homology (SH) domains 2 and 3. PMID- 7773740 TI - Structure and function of restriction endonucleases. AB - Structures of two restriction endonucleases, BamHI and PvuII, were reported in the past year. This doubles the number of restriction endonuclease structures now known from two to four, and enables a comparative analysis of their structures and modes of DNA recognition. Despite a lack of sequence homology between the enzymes, BamHI turns out to resemble EcoRI, and PvuII turns out to resemble EcoRV. The active-site regions are structurally similar in all four enzymes, but their mechanisms of cleavage may differ. PMID- 7773742 TI - Protein-nucleic acid interactions. PMID- 7773741 TI - Four-helix bundle growth factors and their receptors: protein-protein interactions. AB - Many growth factors and cytokines promote receptor clustering on binding. At least three different protein-protein interaction sites are involved: cytokine receptor I, cytokine-receptor II and receptor I-receptor II. Although structural data on these complexes are limited, recent structural and mutagenesis studies of the four-helix bundle class of cytokines are clarifying the nature of the complexes formed. PMID- 7773743 TI - Folding and binding. PMID- 7773744 TI - DNA repair proteins. AB - DNA repair proteins act to correct mutagenic and toxic DNA damage, which can lead to cancer, aging and death. These proteins and their mechanisms of action have been found to be widely conserved between species, often from bacteria to man. Structural and biochemical studies on several bacterial enzymes involved in direct reversal and base excision repair have provided insights into the molecular basis of the recognition of damaged DNA and have also highlighted the novel roles that transition metals play in DNA repair. PMID- 7773745 TI - DNA topoisomerases. AB - In the past year, the atomic structures of three fragments of type I DNA topoisomerases were elucidated. Together with the atomic structure of a fragment of bacterial gyrase, this wealth of structural information is helping to further our understanding of the mechanism of action of topoisomerases. PMID- 7773746 TI - DNA modification by methyltransferases. AB - Enzymatic methylation of DNA plays important roles in both prokaryotes and eukaryotes. Structural study of the HhaI DNA methyltransferase has provided considerable insight into the chemistry of C5-cytosine methylation. The DNA protein complex reveals a substrate cytosine flipped out of the double helix during the reaction, and a novel two-loop DNA-binding motif used for both sequence recognition and flipping the base. Structural comparison of HhaI C5 cytosine methyltransferase, TaqI N6-adenine methyltransferase, and catechol O methyltransferase reveals a common catalytic domain structure, which might be universal among S-adenosyl-L-methionine (SAM)-dependent methyltransferases. PMID- 7773747 TI - Aminoacyl-tRNA synthetases. AB - Detailed mechanisms for each step of the reaction catalyzed by both class I and class II aminoacyl-tRNA synthetases have been proposed on the basis of crystallographic data of aminoacyl-tRNA synthetases in complex with their different substrates. Despite the very different topologies of the two classes, there are striking and unanticipated chemical similarities between their active sites and proposed mechanisms. PMID- 7773748 TI - Theoretical studies of protein folding and unfolding. AB - The mechanism of protein folding is being investigated theoretically by the use of both simplified and all-atom models of the polypeptide chain. Lattice heteropolymer simulations of the folding process have led to proposals for the folding mechanism and for the resolution of the Levinthal paradox. Both stability and rapid folding have been shown in model studies to result from the presence of a pronounced global energy minimum corresponding to the native state. Concomitantly, molecular dynamics simulations with detailed atomic models have been used to analyze the initial stages of protein unfolding. Results concerning possible folding intermediates and the role of water in the unfolding process have been obtained. The two types of theoretical approaches are providing information essential for an understanding of the mechanism of protein folding and are useful for the design of experiments to study the mechanism in different proteins. PMID- 7773749 TI - Structures of folding intermediates. AB - The past year has yielded important results in the study of protein-folding intermediates. It has been shown that the equilibrium molten globule has a native like tertiary fold and is separated from the unfolded state by a first-order phase transition. New equilibrium intermediates have been revealed and substantial progress has been made in the understanding of two main barriers in protein folding. PMID- 7773750 TI - Characterizing transition states in protein folding: an essential step in the puzzle. AB - Transition states in protein folding are being analyzed experimentally and by computer simulation to reveal the sequence of events in the folding and unfolding of proteins at high resolution. Results of this analysis have enabled the reconstruction of folding pathways in vitro and open the prospect of analyzing pathways in vivo. PMID- 7773751 TI - The formation of protein disulphide bonds. AB - The past year has provided more detail on the formation of native disulphide bonds during protein folding at biosynthesis and has identified important cellular factors in the oxidative folding compartments, namely the eukaryotic endoplasmic reticulum and the bacterial periplasm. This information has enabled traditional in vitro refolding studies to be re-evaluated and their relevance as models for folding in the cell to be established. PMID- 7773752 TI - Molecular chaperones in cellular protein folding. AB - Protein folding in the cell requires molecular chaperones. The chaperone proteins of the hsp70 and hsp60 (chaperonin) classes stabilize unfolded or partially folded polypeptides, thereby preventing aggregation, and mediate folding to the native state in ATP-dependent reactions. Recent advances include a more detailed understanding of the mechanistic principles of hsp70 and hsp60 action, the solution of the crystal structure of the chaperonin GroEL, and the definition of pathways of chaperone-mediated protein folding. PMID- 7773753 TI - Amyloidosis. PMID- 7773754 TI - Skin fold dermatitis. PMID- 7773755 TI - Lumbosacral transitional vertebra and thoracic limb malformations in a Chihuahua puppy. AB - A three-month-old, male Chihuahua puppy with congenital absence of the distal 40% of the right thoracic limb was examined. The limb ended as a short, rounded, skin covered stump. Radiography revealed a 40% shortened humerus tapered to a blunt end without its distal extremity. Dissection of the left thoracic limb identified luxation of the elbow joint and absence of the fourth digital pad. Alizarin-red staining and clearing demonstrated syndactylous fourth and fifth digits in the left thoracic limb and an anomalous eighth lumbar vertebra. This additional vertebra was unilaterally sacralized and constituted a lumbosacral transitional vertebra. PMID- 7773756 TI - The canine cemented modular total hip prosthesis. AB - Total hip replacement (THR) is well established as a treatment modality for dogs with noninfectious, nonneoplastic, disabling conditions of the coxofemoral joint. Since the mid 1970s, a fixed-head prosthesis has been used in this procedure. A modular prosthesis, which is based on many of the technical advances found in human prostheses, now is available for use in veterinary medicine. The prosthesis, surgical instrumentation, surgical technique, and clinical results have been evaluated in a prospective study conducted at The Ohio State University's College of Veterinary Medicine. The modular prosthesis provides results equal to or better than the fixed-head prosthesis. PMID- 7773757 TI - Radiographic anatomy of the medial coronoid process of dogs. AB - Mediolateral, flexed mediolateral, mediocaudal-laterocranial 15 degrees oblique (extended and supinated mediolateral), and craniolateral-caudomedial 20 degrees to 30 degrees oblique radiographs of 16 elbow-joint specimens were produced to study the radiographic anatomy of the medial coronoid process. On the mediolateral view, the cranial point of the coronoid process was at the level of the distal one-third of the radial epiphysis. Degree of superimposition of the proximal radius and ulna determined how the medial coronoid process was projected on the radiographs. Mediocaudal-laterocranial oblique radiographs best showed the cranial outline of the medial coronoid process with moderate superimposition of the proximal radius and ulna. PMID- 7773758 TI - Fatal reexpansion pulmonary edema in a kitten following surgical correction of pectus excavatum. AB - Fulminant, fatal pulmonary edema developed in an eight-week-old kitten following external splint correction of severe pectus excavatum. History, signalment, onset of clinical signs, and gross pathological findings were most compatible with a diagnosis of reexpansion pulmonary edema (RPE). This report presents case findings and a literature review of RPE. PMID- 7773759 TI - A simplified method for stabilization of flail chest injuries in small animals. AB - Two dogs and one cat with flail chest injuries were treated by a new technique of external thoracic wall stabilization using a single circumcostal suture for each affected rib and a splint device. Application of the splint device was quick and required minimal manipulation of the patient. Stabilization of the flail chest resulted in improved respiration in each animal. The splint device was left in place in two of the animals as the sole means of rib fixation. No evidence of infection or other adverse effects were noted with this technique. PMID- 7773760 TI - Sacral fractures in dogs: a review of 32 cases. AB - Sacral fractures have not been described well in dogs. The records of 32 dogs diagnosed with sacral fractures were evaluated for neurologic deficits at presentation and discharge. Follow-up was in the form of telephone survey or physical examination at recheck. A score was assigned for each dog at presentation, discharge, and follow-up (0 for normal, 1 for minor deficits, and 2 for major deficits). Fractures located lateral to the sacral foramina were called abaxial, and those medial to the sacral foramina were called axial. Axial fractures had significantly more severe deficits at presentation (p = 0.00017) and discharge (p = 0.03063), but not at follow-up. Neurologic status did not improve significantly during hospitalization in either fracture group, but had improved significantly at follow-up. PMID- 7773761 TI - Subcutaneous administration of desoxycorticosterone pivalate for the treatment of canine hypoadrenocorticism. AB - Twelve dogs with hypoadrenocorticism were treated with subcutaneous desoxycorticosterone pivalate (DOCP). Eight of these dogs were recently diagnosed and had not yet been treated. Four dogs previously had been diagnosed and treated (three with intramuscular DOCP, one with oral fludrocortisone acetate). History, physical examination, serum electrolytes, and blood urea nitrogen (BUN) were evaluated. Desoxycorticosterone pivalate (2.2 mg/kg body weight) was administered every 25 days. On day 0, recently diagnosed dogs had a median serum sodium concentration of 131.5 mEq/L, median serum potassium concentration of 6.6 mEq/L, and median BUN of 41.5 mg/dl. All subsequent median serum electrolyte and BUN concentrations were normal. All previously treated dogs had normal blood values which were maintained throughout the study. PMID- 7773762 TI - Diagnostic and therapeutic considerations in a hypercalcemic dog with multiple endocrine neoplasia. AB - Hypercalcemia was found in a dog examined for episodic weakness and disorientation. A right adrenal mass identified on abdominal ultrasonographic examination was diagnosed as a pheochromocytoma based on increased 1231 metaiodobenzylguanidine uptake and characteristic histopathological features. Serum intact parathyroid hormone (iPTH), total serum calcium, and ionized serum calcium were increased prior to surgery. Although both total and ionized serum calcium concentrations decreased to within normal reference ranges following surgery through postoperative day 17, subsequent high concentrations with increased serum iPTH concentrations confirmed concurrent primary hyperparathyroidism. A right parathyroid tumor was suspected based on a technetium-99m-sestamibi (99mTc-sestamibi) scan. PMID- 7773763 TI - Hemobartonella felis infection with atypical hematological abnormalities. AB - Two cases of clinical feline hemobartonellosis with dramatic hematological changes are reported. One cat succumbed to an acute, severe hemolytic anemia accompanied by markedly increased numbers of nucleated erythrocytes. The second cat presented with a remarkably elevated leukocyte count and responded well to treatment with tetracycline. In both instances, the initial hematological data was very unusual for feline hemobartonellosis. These cases further exemplify the greatly variable and sometimes misleading hematological changes seen with Hemobartonella felis infection. PMID- 7773764 TI - Successful treatment of regional enteritis in a dog. AB - Regional enteritis was diagnosed in an 11-year-old, spayed female German shepherd dog with a history of intermittent vomiting and anorexia. Segmental, transmural granulomatous enteritis involved the pylorus, jejunum, and ileum. The jejunal lesions were excised. The remaining lesions completely resolved subsequent to long-term prednisone and sulfasalazine therapy. PMID- 7773765 TI - Canine neosporosis: a case report and literature review. AB - A three-year-old, intact female vizsla presented for signs of an acute-onset, progressive spinal cord disease. Postmortem examination revealed multifocal central nervous system (CNS) lesions, severe pneumonia with pulmonary edema, and congestion of the liver. Protozoal cysts were found in multiple spinal cord and brain stem sections. Immunohistochemical staining positively identified these cysts as Neospora caninum. A literature review of Neospora caninum infection in the dog with summary of the pathogenesis, clinical signs, diagnostic evaluation, treatment success, and pathology is presented to provide the clinician with an overview of this increasingly prevalent disease. PMID- 7773766 TI - That was the year that was. PMID- 7773767 TI - Backwards and forwards binding. PMID- 7773768 TI - How chaperones tell wrong from right. PMID- 7773769 TI - When lectin meets oligosaccharide. PMID- 7773770 TI - Ribozyme revealed. PMID- 7773771 TI - Snail and spider toxins share a similar tertiary structure and 'cystine motif'. PMID- 7773772 TI - Structure-activity relationships for P-type calcium channel-selective omega agatoxins. PMID- 7773773 TI - Picture story. Birds of a feather. PMID- 7773774 TI - De novo design of integral membrane proteins. AB - We have designed integral membrane proteins with one, two and four hydrophobic transmembrane segments of highly simplified amino acid composition and with appropriately placed positively charged lysine residues intended to control the overall membrane orientation. When expressed in Escherichia coli, these model proteins insert efficiently into the inner membrane and adopt the predicted topologies. This demonstrates the feasibility of de novo design of multi-spanning integral membrane proteins, and opens up new possibilities for membrane protein engineering. PMID- 7773775 TI - Crosslinking of mammalian lectin (galectin-1) by complex biantennary saccharides. AB - Galectins are beta-galactoside-binding proteins that occur intra- and extracellularly in many animal tissues. They have been proposed to form networks of glycoconjugates on the cell surface, where they may modulate various cell response pathways such as growth, activation and adhesion. The high resolution X ray crystallographic analyses of three crystal forms of bovine galectin-1 in complex with biantennary saccharides of N-acetyllactosamine type reveal infinite chains of lectin dimers cross-linked through N-acetyllactosamine units located at the end of the oligosaccharide antenna. The oligosaccharide adopts a different low energy conformation in each of the three crystal forms. PMID- 7773776 TI - Solution structure of the ets domain of Fli-1 when bound to DNA. AB - Members of the ets family of transcription factors share a conserved DNA-binding domain, the ets domain. By using multidimensional NMR, we have determined the structure of the ets domain of human Fli-1 in the DNA-bound form. It consists of three alpha-helices and a four-stranded beta-sheet, similar to structures of the class of helix-turn-helix DNA binding proteins first found in the catabolite activator protein of Escherichia coli. NMR and mutagenesis experiments suggest that in comparison to structurally related proteins, the ets domain uses a new variation of the helix-turn-helix motif for binding to DNA. PMID- 7773777 TI - Solution structure of the tetrameric minimum transforming domain of p53. AB - We report the solution structure of the minimum transforming domain (residues 303 366) of human p53 (p53tet) determined by multidimensional NMR spectroscopy. This domain contains a number of important functions associated with p53 activity including transformation, oligomerization, nuclear localization and a phosphorylation site for p34/cdc2 kinase. p53tet forms a symmetric dimer of dimers that is significantly different from a recent structure reported for a shorter construct of this domain. Phosphorylation of Ser 315 has only minor structural consequences, as this region of the protein is unstructured. Modelling based on the p53tet structure suggests possible modes of interaction between adjacent domains in full-length p53 as well as modes of interaction with DNA. PMID- 7773778 TI - Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos. AB - Src-homology 3 (SH3) domains mediate signal transduction by binding to proline rich motifs in target proteins. We have determined the high-resolution NMR structure of the complex between the amino-terminal SH3 domain of GRB2 and a ten amino acid peptide derived from the guanine nucleotide releasing factor Sos. The NMR data show that the peptide adopts the conformation of a left-handed polyproline type II helix and interacts with three major sites on the SH3 domain. The orientation of the bound peptide is opposite to that of proline-rich peptides bound to the SH3 domains of Abl, Fyn and p85. PMID- 7773779 TI - NMR structure of the N-terminal SH3 domain of GRB2 and its complex with a proline rich peptide from Sos. AB - GRB2 is a small adaptor protein of 217 amino acids comprising one SH2 domain surrounded by two SH3 domains. GRB2 couples receptor tyrosine kinase activation to Ras signalling by interacting, through its SH3 domains, to the carboxy terminal proline-rich regions of the guanine nucleotide exchange factor Sos. Here we report the synthesis and solution structure of the amino-terminal SH3 domain of GRB2 and of its more stable Ser 32 mutant. 1H NMR analysis of the complex between the Ser-32-GRB2-N-SH3 domain and the proline-rich peptide VPPPVPPRRR, derived from h-Sos, shows that relative to the SH3 peptide complexes described for PI3K, Fyn and Abl, the proline-rich peptide in this complex binds in the opposite orientation. PMID- 7773780 TI - Structure determination of racemic trichogin A IV using centrosymmetric crystals. AB - Direct methods of crystal structure solution are greatly facilitated in centrosymmetric space groups where the complexity of the phase-problem is reduced. For most peptides and proteins, crystallization in a centrosymmetric arrangement is precluded by an intrinsic dissymmetry due to the constituent chiral amino acid residues. The synthetic accessibility of peptide sequences containing amino acids of either chirality offers the possibility for co crystallization of racemic crystals. We report here the first use of such an approach for the de novo structure determination of a medium-sized molecule, trichogin A IV, which is a constituent of a fungal lipopeptaibol mixture possessing membrane-modifying properties of biological interest. PMID- 7773781 TI - Structural conservation of hypervariable regions in immunoglobulins evolution. AB - Analysis of human and mouse immunoglobulins has shown that five of six hypervariable regions that form the antigen binding site have a small repertoire of main chain conformations (canonical structures). Cartilaginous fishes are the most distantly related species to humans known to have an immune system, their evolutionary lines having diverged 450 million years ago. An analysis of VH and V kappa sequences from these fishes shows that all the main chain structures in their L1, L2, H1 and H2 hypervariable regions, and one of those in the L3 region, are the same as those most commonly found in human and mouse. This implies that the canonical structures occurring most commonly in hypervariable regions arose very early in the stages of the evolution of the immune system. PMID- 7773782 TI - Molecular geography. PMID- 7773783 TI - Integrin binding revealed. PMID- 7773784 TI - A gripping end to NF-kappa B. PMID- 7773785 TI - Re-orientation of retinal in the M-photointermediate of bacteriorhodopsin. PMID- 7773786 TI - Hormone binding site of corticosteroid binding globulin. PMID- 7773787 TI - Picture story. The inverse light-bulb. PMID- 7773788 TI - Conformational constraints in protein degradation by the 20S proteasome. AB - Conformationally stabilized peptides and unfolding intermediates of bovine alpha lactalbumin have been used to define the degree of unfolding required for degradation by 20S proteasomes. It appears that complete unfolding and the absence of disulphide bonds are prerequisites for degradation, suggesting that a relatively narrow opening controls access to the inner proteolytic compartment of the barrel-shaped proteasome. This is corroborated by electron microscopy studies showing that the insulin B-chain, which is otherwise easily degraded, cannot pass the orifice of this putative peptide channel when a Nanogold particle with a diameter of approximately 2 nm is covalently attached to it. PMID- 7773789 TI - Temperature-favoured assembly of collagen is driven by hydrophilic not hydrophobic interactions. AB - It has become almost axiomatic that protein folding and assembly are dominated by the hydrophobic effect. The contributions from this, and other, hydrophilic interactions can now be better distinguished by direct measurement of forces between proteins. Here we report the measurement of forces between triple helices of type I collagen at different temperatures, pH and solute concentrations. We separate repulsive and attractive components of the net force and analyze the origin of the attraction responsible for the collagen self-assembly. In this case the role of the hydrophobic effect appears to be negligible. Instead, water mediated hydrogen bonding between polar residues is the most consistent explanation. PMID- 7773790 TI - A novel variant of the catalytic triad in the Streptomyces scabies esterase. AB - The crystal structure of a novel esterase from Streptomyces scabies, a causal agent of the potato scab disease, was solved at 2.1 A resolution. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases. The active site contains a dyad of Ser 14 and His 283, closely resembling two of the three components of typical Ser-His-Asp(Glu) triads from other serine hydrolases. Proper orientation of the active site imidazol is maintained by a hydrogen bond between the N delta H group and a main chain oxygen. Thus, the enzyme constitutes the first known natural variation of the chymotrypsin-like triad in which a carboxylic acid is replaced by a neutral hydrogen-bond acceptor. PMID- 7773791 TI - Implications for viral uncoating from the structure of bovine enterovirus. AB - We have determined the crystal structure of a bovine enterovirus, revealing that the topologies of the major capsid proteins and the overall architecture of the virion are similar to those of related picornaviruses. The external loops joining beta-strands are truncated and the canyon region is partially filled by an extension of the VP3 G-H loop giving the viral capsid a relatively smooth appearance. These changes may have implications for cell attachment. In spite of these differences the virus maintains a hydrophobic pocket within VP1, occupied by a specific 'pocket factor' which appears to be myristic acid. These observations support the proposal that a kinetic equilibrium exists between occupied and unoccupied pocket states, with occupation inhibiting uncoating. PMID- 7773792 TI - Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase. AB - A major problem in the development of antiviral therapies for AIDS has been the emergence of drug resistance. We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor. Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1' subsites. Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1' subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic. PMID- 7773793 TI - Postinjury neutrophil priming and activation states: therapeutic challenges. AB - Both hyperactivity and hypoactivity of neutrophils (PMNs) have been implicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regulation of PMN O2- production are reviewed. In addition, relevant research laboratory techniques for measuring both intracellular and extracellular O2- release are outlined. In a pilot study PMN O2- release in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activated, and unresponsive. PMNs from normal adult volunteers are in the resting state. In contrast, PMNs from patients with severe torso trauma are primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating factor and N-formyl methyl-leucyl-phenylalanine) and receptor-independent (phorbol 12-myristate 13 acetate) activation. The ability to identify at-risk patients and provide a rationale for ameliorating PMN-mediated tissue injury in patients with hyperinflammation syndromes are discussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity for increasing PMN function in these patients in order to reduce the risk of sepsis, are also discussed. PMID- 7773794 TI - Optimal preoperative titrated dosage of hypertonic-hyperoncotic solutions in cardiac risk patients. AB - Hypertonic-iso/hyperoncotic solutions have been the subject of numerous studies, mostly used in a fixed dosage (4 mL/kg bw or 250 mL). Nearly no study exists to prove whether this is the appropriate dosage especially in cardiac risk patients with accompanying diseases. We have compared preoperative volume loading with either 10% hydroxyethyl-starch/7.5% NaCl (HHT-HES) or 10% hydroxyethyl-starch/.9% NaCl (HES) in 50 mL bolus infusions. Volume loading was done with either HES or HHT-HES in 2 x 20 patients before aortic aneurysmectomy. The endpoint of stepwise infusion represented the highest cardiac index (CI) at the lowest possible wedge pressure (PCWP) (turning point of each individual Frank Starling relation). 167.5 mL (+/- 45.5 mL = 2.41 mL/kg bw) of HHT-HES and 440 mL (+/- 26.15 mL = 6.33 mL/kg bw) of HES were necessary. We observed a significant higher increase of the CI in the HHT-HES group. Significant increases of PCWP, pulmonary artery pressure, and central venous pressure occurred within the groups without any significant differences between the groups (p < .05). Results of the study showed: 1) The commonly used fixed dosage of 4 mL/kg bw of HHT-HES is too high in cardiac risk patients with slight hypovolemia. 2) HHT-HES should be given in an individual titration. 3) In the HHT-HES group we observed a positive inotropic effect (higher CI). 4) With the individual titration of HHT-HES no negative side effects occurred (especially no hypotension). PMID- 7773795 TI - Tumor necrosis factor antibody treatment of septic baboons reduces the production of sustained T-cell suppressive factors. AB - Post-traumatic septic complications result from impaired cell-mediated immune function, which is caused in part by circulating T-cell suppressive factors (TSFs). We examined whether tumor necrosis factor alpha (TNF-alpha) antibody treatment in a baboon sepsis model influences the production of TSFs, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Sepsis was induced in anesthetized baboons by Escherichia coli infusion, and caused an increase in plasma levels of TNF, TSF activity, IL-10, and active TGF-beta, as well as a decrease in latent TGF-beta. TNF antibody pretreatment reduced TNF levels by 98%. Transient TSF activity (0-4 h) was only marginally influenced, while sustained TSF activity (8-24 h) was markedly reduced. TSF activity at 24 h correlated with peak TNF levels. IL-10 levels, coinciding with early TSF activity, remained unchanged by anti-TNF treatment. Levels of active TGF-beta and the drop in latent TGF-beta were decreased. We conclude that anti-TNF treatment reduces sustained TSF activity and may partially restore impaired cell-mediated immune function. PMID- 7773796 TI - Injury to adult human dermal microvascular endothelial cells in vitro. AB - Adult human dermal microvascular endothelial cells maintained in culture for four to eight passages after isolation were injured by activated human neutrophils but were not injured by unstimulated cells. Injury was cytotoxic as indicated by release of 51Cr from prelabeled cells. Injury was partially inhibited with catalase, dimethylthiourea, and deferoxamine, but was not blocked by superoxide dismutase. Injury was enhanced following pretreatment with iron bound to the membrane-permeable chelator 8-hydroxyquinoline, while neither iron alone nor the chelator by itself enhanced injury. These data suggest that injury results from the generation of hydrogen peroxide by the activated neutrophils and its conversion to hydroxyl radical through an iron-dependent mechanism. These cells appear to be similar to human umbilical vein endothelial cells (HUVEC) in sensitivity to oxidant-induced injury. However, unlike HUVEC, these cells do not show the age-dependent decrease in sensitivity to killing by activated neutrophils that is a characteristic feature of HUVEC. Nor do they show the same increase in spontaneous lysis as a function of age that is characteristic of HUVEC. PMID- 7773797 TI - Acinar cell respiration in experimental acute pancreatitis. AB - The early pathogenetic steps that finally lead to acinar cell necrosis in acute pancreatitis have been characterized only scarcely as yet. Among a lot of hypotheses, one concept favors disturbances of cellular energy metabolism as a major factor that contributes to preterm cell decline. To investigate, whether an experimental acute pancreatitis alters cell respiration, the respiratory capacities of acinar cells isolated from rats with acute pancreatitis were measured. Acute pancreatitis was induced using Popper's model, i.e., a combination of duct obstruction, secretory stimulation, and mesenteric short-term ischemia with subsequent reperfusion. Acinar cells were isolated using a collagenase digestion technique. The respiratory rates of the isolated cells in suspension were measured at 37 degrees C in 100% oxygen-saturated N-(2 hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-buffered Eagle's-minimal essential medium. Resting respiration of the acinar cells uniformly amounted to about 60 pmol of O2/s x 10(6) cells in both the control and the pancreatitis group. Cellular respiration could significantly be stimulated by stepwise uncoupling of oxidative phosphorylation by means of 2,4-dinitrophenol in all cell suspensions investigated. The maximum rate of stimulated respiration was diminished in the cells isolated from rats with acute pancreatitis as compared with the controls (79.3 +/- 5.0 vs. 160.2 +/- 15.5 pmol of O2/s x 10(6) cells, p < .05), however. This reduced respiratory load capacity of the acinar cells in acute pancreatitis reflects the restricted ability of the cells to increase respiration on enhanced cellular demand. Since mitochondrial respiration is coupled to oxidative phosphorylation, an altered energy-transforming potential of the acinar cells in acute pancreatitis becomes evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773798 TI - Blood-to-tissue albumin transport in rats subjected to acute hemorrhage and resuscitation. AB - Hemorrhage induces a rapid redistribution of protein from extravascular spaces into the blood. We studied the effects of acute, nontraumatic hemorrhage on tracer-albumin clearances into individual tissues of rats to determine if reduced protein extravasation could account for intravascular protein gain. Three groups were studied: 1) HEM animals were anesthetized with pentobarbital sodium and bled to a mean arterial pressure of 50 mmHg for 90 min; 2) HEM-RS animals were treated identical to group 1 and then resuscitated with 5% bovine serum albumin (BSA) until baseline arterial pressures were regained; 3) SHAM animals served as time controls. Hemodynamic variables were measured periodically throughout hemorrhage and clearance periods, and plasma samples were collected prior to death for protein and hormone analysis. Plasma clearance of 131I-BSA into individual tissues was measured over the final 30 min of each protocol with a terminal injection of 125I-BSA used to correct for intravascular volume. Reduction of blood volume by 35% in HEM-treated animals resulted in a marked decrease in albumin transport relative to the SHAM group (p < or = .05) in the following tissues: skeletal muscle (-65%), skin (-49%), ileum (-75%), cecum (-66%), colon ( 67%), heart (-67%), and lung (-71%). Significant changes were not observed in the remaining tissues sampled: pancreas, kidney, and cerebrum. Albumin clearances in the HEM-RS group were slightly but not significantly lower than SHAM animals except for skeletal muscle, where transport remained depressed following resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773799 TI - Lipopolysaccharide induces intracytoplasmic migration of the polymorphonuclear leukocyte CD11b/CD18 receptor. AB - We investigated the effects of lipopolysaccharide (LPS) on the subcellular location of the integrin receptor CD11b/CD18 (Mac-1). Cytoplast and subcellular fractionation experiments were performed to distinguish between receptor shedding and intracellular receptor transport as mechanisms involved for the effects of LPS on CD11b/CD18 expression. Cytoplast preparations demonstrated the same percentage of cell-associated receptors +/- LPS. Subcellular fractionation experiments demonstrated a shift from primarily plasma membrane fractions to azurophilic granules. Protein tyrosine kinase inhibition with genistein (50 microM) inhibited the LPS-induced translocation of CD11b/CD18 receptors to azurophilic granules. The effects of LPS (10 ng/mL) alone were reproduced with LPS (.1 ng/mL) plus heat-inactivated pooled normal human serum. Preincubation of PMN with anti-CD14 monoclonal antibodies prevented the effects of LPS+serum on the translocation of CD11b/CD18 receptors. These results demonstrate that LPS regulates CD11b/CD18 expression by inducing intracytoplasmic translocation of this receptor to azurophilic granules. This process involves activation of protein tyrosine kinase, and endosomal acidification contributes to the degradation of these receptors within azurophilic granules. PMID- 7773800 TI - Reciprocal expression of phosphoenolpyruvate carboxykinase and acute phase genes during acute inflammation. AB - Part of the hepatic response to injury is mediated by the expression of a gene family known as acute phase genes. Expression of acute phase genes is induced by the presence of cytokines in the circulation such as tumor necrosis factor alpha, interferon gamma, and interleukins-1 and -6. Simultaneous with the transcription of acute phase genes, there is a decrease in the expression of other genes such as albumin. In the present study, we report the decrease in transcription of the gene coding for phosphoenolpyruvate carboxykinase (PEPCK), a key regulatory enzyme in the gluconeogenic pathway, in rat liver during an acute inflammatory state induced by bacterial endotoxin. Steady-state mRNA levels of PEPCK decrease 3 h after endotoxin injection, returning to 70% of normal levels after 24 h. This decrease in PEPCK mRNA levels was due to a decline in the rate of transcription of the gene, most likely mediated by an increase in the circulating levels of insulin. However, expression of the PEPCK gene was not induced by an increase in the cellular levels of cAMP during inflammation. Such a lack of response to cAMP may be due to the inactivation of, or decrease in, the levels of the transcriptional factor(s) responsible for PEPCK transcription. PMID- 7773801 TI - Pentoxifylline improves survival and reduces tumor necrosis factor, interleukin 6, and endothelin-1 in fulminant intra-abdominal sepsis in rats. AB - The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant intra-abdominal sepsis in rats. Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg/kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24). PTX therapy was started at sepsis induction or after 4 h, and mortality was reduced from 89% in untreated sepsis to 60-66% in the PTX groups. Levels of sepsis mediators were studied in two groups: untreated sepsis and sepsis + PTX 40 mg/kg started 1 h after sepsis induction. In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6), endothelin-1, lactate, neutrophils, and packed cell volume. Cecal perforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endothelin-1, leading to dehydration, lactacidosis, neutropenia, and death. Treatment with PTX did not modify dehydration, neutropenia, or concentrations of bacteria and endotoxin. Release of endothelin-1 was delayed, TNF burst was nearly abolished, and levels of IL-6 and lactate were substantially suppressed. In summary, PTX improves survival and reduces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fulminant intra-abdominal sepsis in rats. The primary effect of PTX in this sequence is probably reduction of TNF. PMID- 7773802 TI - Lack of direct endotoxin-induced vasoactive effects on isolated skeletal muscle arterioles. AB - Septic shock continues to be a major cause of mortality in the intensive care unit. This study was conducted to determine if endotoxin exerts a direct effect on the major determinant of peripheral vascular resistance, skeletal muscle arterioles. First order cremasteric arterioles were isolated from male Sprague Dawley rats, cannulated with glass micropipettes, superfused in physiologic saline solution, and allowed to achieve spontaneous basal tone in the absence of intraluminal flow. Phenylephrine responsiveness was assessed before and after exposure to 2.5 micrograms/mL Salmonella enteritidis endotoxin (ET) for 1-2 h. There was no change in either basal diameter (91 +/- 5 microns before ET and 98 +/- 5 microns after ET) or phenylephrine responsiveness. In vivo exposure to ET (15 mg/kg) resulted in no change in basal tone at 1 h, however increased tone was observed in arterioles harvested after 4 h of systemic ET (43 +/- 4% without ET and 57 +/- 3% with, p < .05). To determine if upstream conduit vessels released factors responsible for the vasodilation of skeletal muscle arterioles, isolated cannulated cremasteric arterioles were connected in series to a 1 cm segment of aorta and superfused without and with 2.5 micrograms/mL ET. An increase in basal diameter was observed in arterioles from 94 +/- 14 microns before ET to 120 +/- 17 microns after ET (p < .05). These studies demonstrate that ET has no direct effect on isolated cannulated skeletal muscle arterioles, and that a vasodilating substance not consistent with nitric oxide is released from the upstream arterial bed. PMID- 7773803 TI - Amrinone combined with dobutamine improves hemodynamics and oxygen delivery without down-regulation of cardiac beta-adrenergic receptor density in porcine endotoxemia. AB - Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O2 delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia coli lipopolysaccharide (endotoxin) or equivolumetric .9% NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T = 120-240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 micrograms/kg/min) (AMRlow); DOB (10 micrograms/kg/min) (DOB); AMR infusion (40 micrograms/kg/min) + DOB (AMRlow+DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 micrograms/kg/min) (AMRhigh); or AMR bolus (.75 mg/kg) followed by infusion (40 micrograms/kg/min) + DOB (AMRhigh+DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for beta-adrenergic receptor analysis. Endotoxin significantly (p < .05) decreased cardiac index, right ventricular ejection fraction, stroke volume index, maximum rate of rise of left ventricular pressure (dP/dtmax), mean arterial pressure, and O2 delivery, and increased pulmonary vascular resistance and mean pulmonary arterial pressure (p < .05). AMRlow+DOB significantly (p < .05) increased cardiac index, dP/dtmax, right ventricular ejection fraction, stroke volume index, O2 delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. beta-Adrenergic receptor density (Bmax) and binding equilibrium dissociation constant (KD) for [3H]dihydroalprenolol were not affected by endotoxin or any treatment (p < .05). Endotoxin-induced hemodynamic deterioration and decreased O2 delivery was attenuated by AMRlow+DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O2 delivery complicated by pulmonary hypertension. PMID- 7773804 TI - The 18th Annual Conference on Shock. Asheville, North Carolina, June 11-14, 1995. Abstracts. PMID- 7773806 TI - Development: on whose terms? PMID- 7773805 TI - Measurement methods to determine compliance with ambient air quality standards for suspended particles. AB - One of the most important parts of formulating a National Ambient Air Quality Standard is specifying the measurement methods for determining and attaining compliance. The samples taken for compliance are often pushed beyond their original purpose to identify sources, to evaluate the effectiveness of controls, and to determine relationships between pollution levels and public health. A full understanding of available sampling and analysis methods is needed, as well as an analysis of their costs, before acceptable monitoring approached can be specified. This review identifies issues related to measurement methods used to determine compliance with standards, describes current and future measurement methods and their limitations, and determines the extent to which existing technology can meet short-term and long-term needs for measuring compliance. PMID- 7773807 TI - AIDS in Manila, Philippines. PMID- 7773808 TI - After the storm: an American nurse visits Vietnam. PMID- 7773809 TI - Nursing education in Russia: visions and realities. PMID- 7773810 TI - Mission to Honduras. PMID- 7773811 TI - Self-care of older black adults in a South African community. PMID- 7773812 TI - Romania: a nursing journey. PMID- 7773813 TI - Latvia: nursing reborn. PMID- 7773815 TI - Continuous passive motion in rehabilitation after anterior cruciate ligament reconstruction. AB - In a prospective, randomized study, 34 patients (25 male, 9 female; mean age 27 +/- 8 years) with unilateral anterior cruciate ligament ruptures and arthroscopic reconstruction with patellar tendon grafts were allocated at random to either early active motion only (AM; n = 17) or active motion in combination with continuous passive motion (CPM; n = 17). Range of motion was measured with a goniometer and joint swelling with a tape measure, preoperatively and at 6 weeks postoperatively. Neither associated injuries nor the age of the patients differed in the two groups. There was no difference in the range of motion between the two groups at 6 weeks' follow-up. Joint swelling was more pronounced in the AM group both preoperatively and at 6 weeks' follow-up. In this investigation the range of motion was not improved by CPM. The difference in joint swelling between the two groups may be explained by a persistent preoperative variation in joint effusion due to an imbalanced distribution of acute and chronic cases. PMID- 7773814 TI - Anterior cruciate ligament patellar tendon reconstruction: it is probably better to leave the tendon defect open! AB - The purpose of our prospective study was to establish whether or not in anterior cruciate ligament (ACL) patellar tendon reconstruction the tendon defect has to be closed. In 50 consecutive ACL patellar tendon reconstructions, the tendon defect was randomly closed (group I) or left open (group II). The following data were recorded from all patients on the 4th and 14th days post operation: range of motion (ROM), pain at rest, pain and validity at isometric contraction, ability of bent leg raising (at 4th day) and straight leg raising (at 14th day). All the patients underwent ultrasonographic examination after 3 months and X-ray scanning at 6 months post operation. Forty patients underwent a CT-scan examination at 6 months. Thirty patients underwent isokinetic testing between 10 and 12 months post operation. Evaluating the immediate post operation data, no statistically significant differences emerged between the two groups. Ultrasonography showed in 68% of the knees of group I (defect closed) a thickened patellar tendon (PT), while in 60% of group II it was of normal thickness. No patients of either group developed patella infera by X-ray evaluation 6 months post operation. CT scans at 6 months showed that 100% of the knees of group I had a thickened PT in toto (nearly twice as thick as normal). Scar tissue was present not only in its central third but also in more than half of the cases in the medial and lateral third. In group II 75% of the patients had a normal thickness PT and 25% presented with only a minimal thickening. Scar tissue was distinguished only at its central third.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773816 TI - A comparison of clinical and radiological parameters with two arthroscopic techniques for anterior cruciate ligament reconstruction. AB - We performed a comparative study of two series of 25 patellar tendon arthroscopic reconstructions of isolated chronic anterior cruciate ligament injuries, alternating between a double-incision (using a rear-entry guide) or single incision technique (using a transtibial approach). The patients were reviewed to assess the clinical, KT-2000 and radiological differences at an average follow-up of 14 months (range 8-18 months). For the clinical evaluation the International Knee Documentation Committee Form was used. The following radiographic parameters were measured: (1) the direction of the femoral and tibial tunnels in the antero posterior (AP) and lateral (LL) views; (2) the location of the anterior border of the intra-articular exit hole of the femoral tunnel in the LL radiologic view; (3) femoral interference screw divergence with the bone block. An extension loss < or = 5 degrees was detected in 40% of the double-incision and 36% of the single incision patients (NS). A flexion loss < or = 10 degrees was present in 8% of the double-incision and 16% of single-incision group (NS). There were no differences in terms of pivot shift test between the two groups (pivot glide in 12% of both groups). The average side-to-side KT-2000 differences at the manual maximum test were 1.98 mm in the double-incision and 2.64 mm in the single-incision group. With the double-incision technique the femoral and tibial tunnels were divergent in the AP plane and crossed the joint at an angle of 37 degrees and 72 degrees, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773817 TI - The double patella syndrome. AB - First described by A. Trillat, the double patella is an uncommon clinical feature following repetitive injuries of the extensor mechanism of the knee. The first injury is a tendo-periosteal avulsion of the suprapatellar or, less frequently, infrapatellar tendon from the corresponding patellar pole. Often these avulsions are misdiagnosed and therefore treated only with a cast or no immobilization at all. Subsequent giving-way episodes lead to extensive ossification which is adjacent to or separated from the patella. The peculiar shape of this ossification overriding or underlying the primary kneecap justifies the denomination of double patella. Surgical treatment consists of removal of the calcification and reattachment of the tendon to the patella by transosseous sutures. PMID- 7773818 TI - Validation and application of a subjective knee questionnaire. AB - Patients' complaints on limitations in activities of daily living (ADL) and sports are possible signs for various injuries of the knee joint. These complaints can be easily assessed by the patient using a questionnaire with visual analogue scale (VAS) responses. A German translation of the English questionnaire concerning knee complaints [4] has been validated and tested for clinical use. It consists of 28 questions. For the statistical analysis, an overall score (VAS score) of the questionnaire was determined. The validation included an expert evaluation on the content of the questionnaire, a test for the reliability, a comparison with subjective knee scoring systems (Cincinnati score, Lysholm score) and a test on VAS score results in patient groups with various knee injuries (discrimination of patients). For the evaluation of operative treatment results, the responsiveness of the questionnaire was tested in patients undergoing arthroscopic meniscus surgery and anterior cruciate ligament reconstruction. The investigation was conducted prior to the operation, 2, 6, 12 and 24 weeks after surgery for both groups and also 36 weeks after surgery for the cruciate ligament patients. Interviews conducted with knee surgeons (so called knee experts) revealed that 85% judged the questionnaire as being acceptable for clinical use. The reliability of the VAS score for healthy individuals was r = 0.86. The reliability for patients in a postoperative rehabilitation programme was r = 0.92. By means of the VAS score we were able to assess the extent of limitations in knee function in various patient groups with meniscus lesions, insufficiency ot the anterior and posterior cruciate ligaments and chondromalacia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773819 TI - Effect of fibrin glue and endothelial cell growth factor on the early healing response of the transplanted allogenic meniscus: a pilot study. AB - Twentyfour meniscal allotransplantations were conducted in 12 adult mongrel dogs. The medial meniscus was replaced using a deep-frozen meniscal allograft. The junction between the meniscus and capsule was treated in one of the three ways. In the control group, the meniscus was sutured only to the adjacent capsular tissue (group C). In the second group, fibrin glue was injected at the junction (group F), and in the third group, fibrin glue and endothelial cell growth factor (ECGF) were injected at the juncture between the transplanted meniscus and the adjacent capsule before the meniscus was sutured (group FE). Histological observation was performed to investigate the effect of fibrin glue and ECGF on the healing process of transplants at various intervals of 1, 4, 8 and 12 weeks. No immunological response was noted in any of the knees. The healing of the transplanted meniscus was first observed at the peripheral attachment. Also, the pannus-like tissue extended from the synovium to the surface of the meniscus. The healing rate in each group at 1 week and 12 weeks was 22% and 77% in group C, 52% and 80% in group F, and 64% and 80% in group FE, respectively. At 4 and 8 weeks, early cellular repopulation was found in group FE and the area which contained new cells was larger than the acellular central core at 8 weeks. However, there was no difference among the three groups at 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773820 TI - The influence of orthoses on the proprioception of the ankle joint. AB - The ankle joints of 14 healthy volunteers and 16 patients with unstable ankle joints were tested regarding their functional and proprioceptive capabilities. All of them were active athletes. Three tests were used of the study: single-leg stance test, single-leg jumping course test, angle-reproduction test. The influence of three stabilization devices (lace-on-brace/"Mikros", stirrup brace/"Aircast", taping) on the proprioceptivity of stable and unstable ankle joints was evaluated. The scores of the single-leg jumping course without any stabilizing device (category "standard") ranged between 8.06 and 13.68 (10.65 +/- 1.29). In the categories "Mikros" (9.85 +/- 0.99), and "Aircast" (9.99 +/- 1.14) as well as with the tape bandage (10.27 +/- 0.81) better scores were achieved. The differences "standard vs. Mikros" and "standard vs. Aircast" revealed a significant reduction of the scores with orthoses (P < 0.01). The error rate in the single-leg stance test was within the range of 0-16 (5.12 +/- 2.85) for the category "standard". It was lower for the categories "Mikros" (3.65 +/- 2.65) and "Aircast" (4.17 +/- 2.59). The error rate was highest in the group with a tape bandage (5.79 +/- 3.53). The differences "standard vs Mikros" as well as "standard vs. Aircast" were significant (P < 0.01). There was also a significant difference between these categories regarding injured and not injured ankle joints (P < 0.01). The angle-reproduction-test showed higher values for the category "standard" (2.36 degrees +/- 0.97) in comparison to the categories "Mikros" (1.46 degrees +/- 0.72), "Aircast" (1.62 degrees +/- 0.91) and "taping" (1.84 degrees +/- 0.41).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773821 TI - Tibial-talar dislocation without fracture: treatment principles and outcome. AB - The incidence of tibial-talar dislocations without fracture is unknown and has been sparsely reported in the literature. The diagnosis of the injury is straightforward with the appropriate examination and roentgenograms. Good to excellent results can be achieved with open or closed dislocations treated by closed reduction and immobilization for 4-6 weeks. Although open dislocations require irrigation, debridement, and possibly delayed closure, controversy exists with regard to acute ligament repair. Because good to excellent results are possible without acute ligament repair, and delayed repair on reconstruction can be accomplished with good outcomes, we recommend treating these injuries without ligament repair. PMID- 7773822 TI - Arthroscopic shoulder stabilization using Mitek anchors. AB - The purpose of this paper is to report our experience with an arthroscopic stabilization technique using bone anchors in the treatment of chronic unidirectional anterior-inferior shoulder instability. 30 of 32 patients (average age, 26 years) were followed for an average of 24 months (range 12 to 36). There were 28 patients with dislocations and four with subluxations. In the group of the dislocators five patients had more than 10 dislocations and 15 patients between one and seven (average three). In 68% a sport injury was the reason for the first dislocation. Due to the length of the labroligamentous detachment two to four anchors were used for stabilization. According to the criteria of Rowe, in the group of the subluxators (4) two had an excellent and two a good result. In the group of the dislocators (26) two patients dislocated their shoulder again after reconstruction without a new accident, one had a recurrent dislocation from significant trauma. Two of them had an open stabilization afterwards. Overall there were 53.9% excellent, 34.6% good and 11.5% poor results. In 50% there was no restriction of shoulder motion, 21% had a loss of external rotation of 5 degrees and 29% of 10 degrees. Arthroscopic shoulder stabilization with help of Mitek anchors seems to be a good method for treatment of chronic unidirectional anterior-inferior instabilities with less than 10 dislocations preoperatively. All patients, who suffered a spontaneous recurrent dislocation, had more than 10 dislocations before. In these cases this arthroscopic procedure is not suited to restore stability, even if a Bankart-lesion is present. PMID- 7773823 TI - Postoperative analgesic effects of intra-articular bupivacaine and morphine after arthroscopic cruciate ligament surgery. AB - Intra-articular administration of local anaesthetics such as bupivacaine can produce short-term postoperative analgesia in patients undergoing diagnostic arthroscopy or arthroscopic meniscectomy. A peripheral anti-nociceptive effect may also be induced by the administration of intra-articular opiates interacting with local opioid receptors in inflamed peripheral tissue. In the present study we aimed to study the analgesic effects of intra-articularly given bupivacaine and morphine sulphate (as well as the combination of both drugs) on postoperative pain. In a prospective, randomized, double-blind manner 40 patients received one of the following: (a) morphine (1 mg in 20 ml NaCl), (b) bupivacaine (20 ml, 0.375%), (c) combination of both or (d) saline (20 ml, control group) intra articularly at the end of arthroscopic anterior cruciate ligament (ACL) reconstruction. The postoperative pain was assessed via a visual analogue scale (VAS) during the first 48 h after surgery, and supplemental analgesic requirements were noted. All comparisons were made versus the control group receiving saline. The pain scores were significantly lower in the morphine group at 24 and 48 h, and in the bupivacaine group at 2, 4 and 6 h after surgery. In the group that received a combination of both bupivacaine and morphine, the pain scores were significantly reduced throughout the whole postoperative observation period. No side-effects or complications from therapy were seen in any of the groups. The conclusion of this study is that intra-articular morphine is effective in the postoperative period after arthroscopic ACL reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773824 TI - Effect of knee flexion on the in situ force distribution in the human anterior cruciate ligament. AB - This study was conducted to evaluate the effect of applied load on the magnitude, direction, and point of tibial intersection of the in situ forces of the anteromedial (AM) and posterolateral (PL) bands of the human anterior cruciate ligament (ACL) at 30 degrees and 90 degrees of knee flexion. An Instron was used to apply a 100 N anterior shear force to 11 human cadaver knees, 6 at 30 degrees of knee flexion and 5 at 90 degrees of knee flexion. A Universal Force Sensor (UFS) recorded the resultant 6 degree-of freedom (DOF) forces/moments. Each specimen then underwent serial removal of the AM and PL bands. With the knee limited to 1 DOF (anteroposterior), tests were performed before and after each structure was removed. Because the path was identical in each test, the principle of superposition was applied. Thus, the difference between the resultant forces could be attributed to the force carried by the structure just removed. The magnitudes of force in the ACL at 30 degrees and 90 degrees of knee flexion were 114.1 +/- 7.4 N and 90.8 +/- 8.3 N, respectively (P < 0.05). At 30 degrees, the AM and PL bundles carried 95% and 4% of the total ACL force, respectively. At 90 degrees, the AM and PL bands carried 85% and 13%, respectively (P < 0.05). The direction of the in situ force in the whole ACL as well as its two bands correlated with the anatomic orientation of the ligament.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7773825 TI - [Diagnostic house call within the scope of inpatient geriatric assessment]. AB - The value of a diagnostic home visit as part of hospital-based geriatric assessment was examined in a prospective study. 141 subjects admitted from home to the geriatric hospital and showing functional decline with risk of nursing home placement underwent a comprehensive geriatric assessment and a diagnostic home visit. In 19.1% of the patients, the diagnostic visit resulted in a change of time, and in 14.9% in a change of location of discharge. Up to seven problems were newly discovered (mean 2.1). To maintain independence up to six technical aids were prescribed (mean 2.3). The most common recommendations were related to safety (59.2% of all cases). In 89.3% the diagnostic home visit was judged necessary by the home intervention team. A follow-up visit after 3 months revealed that about 80% of all recommendations were implemented and approximately the same amount of technical aids were still used. The diagnostic home visit allows individual prescription of technical aids, when necessary. It contributes meaningful information to the geriatric assessment process and helps to achieve successful in-hospital therapy and discharge planning. It can be recommended especially for elderly patients at risk for losing their independence. PMID- 7773826 TI - [Discharge from the geriatric clinic: factors predicting independent living at home]. AB - This article presents the predictors for living at home 3 months, 6 months, 12 months, and 24 months after hospitalization in a geriatric clinic. The multivariate regression analysis revealed the predictive factors for living at home after 3 months: Incontinence, functional status judged by the physician, and balance performance. For living at home at 6 months, balance performance, handgrip were predictive, and at 12 months, balance performance, physicians judgement of functional abilities and Barthel-Index had the most predictive value. The only factor that was recognized to be predictive for living at home at 24 months was the physician's judgement of the functional abilities of the patient. It is concluded that the functional status measured by observation but preferably by performance is of predictive value for living at home from 6 months to 12 months after acute hospitalization. PMID- 7773827 TI - [Resident Assessment Instrument (RAI): a system for client evaluation and documentation in long-term care--an overview]. AB - This article describes the interdisciplinary care planning system "Resident Assessment Instrument" (RAI) for nursing homes with its parts, the Health Care Financing Administration mandated "Minimum Data Set" (MDS) and the "Resident Assessment Protocols" (RAPs). The MDS-derived case mix system for resource allocation, the Resource Utilization Groups (RUGs), are mentioned. The prerequisites for an implementation of the F.R.G. are discussed. PMID- 7773828 TI - [The "Geriatric Assessment" Study Group (AGAST): recommendations for the use of assessment procedures]. AB - This work presents preliminary recommendations for a three-step geriatric assessment approach developed by a newly created working group consisting of members from nine geriatric departments in Germany and Switzerland. The recommendations were based on a literature review, expert consultation, and a consensus meeting. As part of this effort, instruments and guidelines for selected geriatric assessment instruments were translated and will be tested in German language. Further research is planned for refining the recommended method. Currently, these recommendations might help to stimulate the spread of geriatric assessment method in German-speaking areas and facilitate joint research projects among geriatric institutions. PMID- 7773829 TI - [Geriatric assessment: possibilities and limits]. AB - A recent meta-analysis has shown that comprehensive geriatric assessment can reduce mortality, increase survival at home, and improve functional status in elderly patients. Despite their high effectiveness, geriatric assessment programs have not yet been widely introduced into clinical practice. This review discusses the following four factors potentially explaining the limited spread of geriatric assessment programs. 1) There is a lack of accepted targeting criteria to select patients who need evaluation and management in costly in patient geriatric units. 2) There are effectiveness gaps in current knowledge on modifiable disability risk factors. 3) Geriatric assessment programs have been insufficiently integrated into the continuity of primary care. 4) More data are needed for evaluating the cost of geriatric assessment. Interdisciplinary research might help to optimize geriatric assessment programs and, at the same time, might ensure access of elderly patients to appropriate geriatric assessment programs despite current restraints in health care costs. PMID- 7773830 TI - [Identification of functional deficits in the acute hospital by geriatric assessment]. AB - Functional deficits of elderly patients are often not recognized during routine treatment in acute hospital care. In Germany, there are only limited experiences with the use of standardized assessment-scales in this health care setting. In this study, 112 patients were recruited for a very broad geriatric assessment focused on methodological and practical questions. There were 38.8% with deficits in the ADL and 12.6% with depressive symptoms. Many patients showed low motivational factors such as energy, efficacy and will. Geriatric syndromes such as malnutrition were also very common. In general, many patients in acute care hospitals have functional deficits which are not recognized by the physicians. For many patients, short instruments are sufficient for screening purposes. The effectiveness of a complete geriatric assessment depends mostly on the use of good selection criteria. PMID- 7773831 TI - [Diagnosis of depression in the elderly. The "Geriatric Depression Scale"]. AB - Psychiatric diseases are very common among elderly people. Depressions rank before dementias in this age group. 2-2.5 million people aged over 65 years are suffering from symptoms of depression in Germany. Patients with Mayor Depression Disease (MDD) have a poor prognosis. MDD should therefore be recognized and treated in community dwelling elderly, in nursing homes and in hospitals. Underdiagnosis of MDD is well documented in the medical literature. Only a quarter of patients with a MDD are detected. By a short screening test for depression such as the Geriatric Depression Scale (GDS) depressed patients can be identified. With a sensitivity and specificity of about 70%. The time needed to perform the short form of the GDS is only 5-7 min. The GDS is an important part of many assessment programs in England and USA. It is also recommended in Germany by the "Geriatric Assessment" working group. PMID- 7773832 TI - Effectiveness of hospital-based geriatric evaluation and management and home intervention team (GEM-HIT). Rationale and design of a 5-year randomized trial. AB - In this ongoing randomized controlled trial the effectiveness of an interdisciplinary team implementing hospital-based comprehensive geriatric assessment (CGA) and home intervention is being studied. All patients admitted from home showing functional decline with impairment of any basic activity of daily living are randomly assigned to one of the following courses of treatment: CGA with in-hospital and post discharge management by a home intervention team (HIT), where necessary (group 1): CGA with recommendations and usual care at home (group 2); or usual hospital and home care (group 3). The HIT consists of 3 nurses, 1 geriatrician, 1 physiotherapist, 1 occupational therapist, and 1 social worker. 540 patients will be recruited for the trial, which will assess the effects of GEM-HIT on the following outcomes: health status, functional status, survival, hospital readmission, nursing home placement and costs. The purpose of the GEM-HIT trial is to answer many of the current questions concerning treatment and health care delivery for frail older persons under the specific conditions found in Germany. The large sample size and the broad range of diagnoses included in the study will allow the evaluation of effects of GEM-HIT for subgroups and may help to identify the most effective assessment tools for use within our particular context. PMID- 7773833 TI - Comprehensive geriatric assessment and medication compliance. AB - Patient compliance is an essential therapeutic factor which is crucial to outcome. There is a recent surge of interest in compliance issues evoked by reliable and feasible measurement methods. In particular, data on real-time dosing facilitate the interpretation of drug effects. This information can be used in patient counseling. Comprehensive geriatric assessment is likely to detect major reasons of non-intentional non-compliance. A medication review should include several questions on patient compliance behavior for which examples are proposed. Systematic geriatric assessment is likely to improve rational prescribing of pharmacotherapy in the elderly. This will also contribute to ensure patients compliance. PMID- 7773834 TI - Gender differences in age-related physiological changes and some diseases. AB - The clinical and laboratory data from a cross-sectional and a longitudinal study of healthy individuals between 50-89 years of age and that of centenarians were compared. The examination showed that in healthy elderly subjects and centenarians most of the clinical laboratory findings were in the normal range. However, age-related changes could be observed in erythrocyte sedimentation rate, in serum albumin level, and in the frequency of rheuma factor. Gender difference could be seen in the HDL-cholesterol level. Age and sex differences were observed in the hematocrit-, and hemoglobin-values, in serum creatinine-, total cholesterol-, serum IgG, IgA, IgM-levels, and in the frequency of the occurrence of antinuclear factor. The examinations demonstrated that lower hemoglobin and hematocrit values, elevated total-cholesterol level, the presence of antinuclear and rheuma factor, and elevated systolic blood pressure were more frequent in females than in males. It could be stated, however, that the mentioned changes did not prevent females from having a longer life span than males. PMID- 7773835 TI - [The main principles of the new nursing care insurance regulation]. PMID- 7773837 TI - Collaboration in nursing: NOLF and NFSNO. PMID- 7773836 TI - [Method and organization of geriatric assessment]. AB - The intention of a Geriatric Assessment (GA) is a more systematic and exact way to examine a wide range of activities of daily life. This can be achieved by the help of scientifically proved and standardized investigations which complete the medical judgment with objective and comparable results. This type of examination controls the selective observation of the investigator and makes reexamination easier. Moreover, this way of gaining information gives reliable hints about non apparent or difficult-to-estimate risks of a patient. The methods of GA have to be adapted to different qualities of resources which will be assessed: physical resources should be assessed by standardized ways of observation; the patient's subjective well-being should be examined by standardized interviews. The standardized instruments of measurement are fairly independent from personal qualifications of the investigator. PMID- 7773838 TI - Prevention works! With the nursing link. PMID- 7773839 TI - Salutogenesis: an organizing structure for addictions nursing. PMID- 7773840 TI - Dual specialization for addiction nurses. PMID- 7773841 TI - The role of the addictions nurse specialist in adult psychiatry. PMID- 7773842 TI - Survey of addiction education of Iowa nursing students. PMID- 7773843 TI - Creative sessions illustrate methods of prevention at 1994 conference. PMID- 7773844 TI - Certification update. PMID- 7773845 TI - Readiness for recovery. PMID- 7773846 TI - Comparison of outcomes between acute care general hospital transfers and direct admissions to a detoxification unit. PMID- 7773847 TI - Alcohol and drug problems in the elderly. PMID- 7773848 TI - Recommendations for fluoride. PMID- 7773849 TI - Immediate implant post-surgical complications. AB - Immediate surgical implants provide a convenient means of replacing missing teeth without requiring hard tissue reduction of restoration-free potential fixed partial denture abutments. Although the procedure is described as "predictable," complications and failures do occur. This report presents four cases of immediate implant complications and their management, and discusses possible causes of the untoward results. Careful pre-operative planning, adequate surgical technique and post-surgical management, timely and suitable loading, and meticulous hygiene maintenance can serve to minimize implant complications and failures. The prospective immediate implant patient must be provided with sufficient information to allow informed consent to be given. Minimal requirements are a description of the procedures in terms the patient can understand, an explanation of potential risks and complications, and adequate disclosure of information about alternative therapies. PMID- 7773850 TI - Effectiveness of a topical antifungal regimen for the treatment of oral candidiasis in older, chronically ill, institutionalized, adults. AB - Because of predisposing systemic disease, the frequent administration of medication, and the use of a complete denture, oral candidiasis is a common problem among older, chronically ill, institutionalized adults. This randomized clinical trial was designed to evaluate the effectiveness of an antifungal denture soaking solution (48 mL nystatin liquid, 100,000 IU/mL, dissolved in 432 mL of distilled water producing 10,000 IU nystatin mL solution), used as an adjunct to a nystatin vaginal lozenge (100,000 IU/g, dissolved in the mouth three times daily for seven days) in a group of older, chronically ill, institutionalized adults. Although the clinical signs and symptoms of oral candidiasis were resolved in all subjects following therapy, the presence of invasive Candida hyphae was detected in approximately 80 per cent of tissue and/or dentures. When compared to tap water, the use of an antifungal denture soaking solution produced no detectable difference in the presence of Candida albicans hyphae over a three-month period (M-H chi-square = 0.021, p = 0.886), but it did reduce the rate of recurrence of clinical signs and symptoms. The appropriateness of this regimen for the treatment of oral candidiasis in this type of patient is challenged. PMID- 7773851 TI - Submerged versus non-submerged dental implants: a comparison. PMID- 7773852 TI - Financially free and fifty something: pipe dream or possibility? (2). PMID- 7773853 TI - How successful is your dental practice?--10 performance criteria. PMID- 7773854 TI - Consent--is it informed and valid? PMID- 7773855 TI - Suicide--no margin for error. PMID- 7773857 TI - Patient education: the key to a successful practice in turbulent times. PMID- 7773856 TI - "Team dynamics 2000": patient care and practice management. PMID- 7773858 TI - Letters count. PMID- 7773859 TI - The future of third-party plans. PMID- 7773860 TI - To spit or expectorate? PMID- 7773861 TI - Informed consent. PMID- 7773862 TI - Making a good first--and lasting--impression. PMID- 7773863 TI - War is an atrocious thing. PMID- 7773864 TI - Ash Temple Limited--a century of service. PMID- 7773865 TI - Orthognathic surgery and the family dentist. AB - In general, orthognathic surgery is a reliable, appropriate and prudent treatment option to correct maxillofacial deformities that cannot be managed by nonsurgical means alone. Unfavorable outcomes are relatively rare, but the statistical frequency of these complications loses its meaning in those cases where they occur. If a complication happens to an individual patient, it represents a one hundred per cent incidence for that individual. For this reason, prior to the provision of treatment it is vitally important to obtain informed consent, ideally by establishing the widest possible information base on which meaningful communication can be built for the patient, the orthodontist, the surgeon, and the family dentist. PMID- 7773866 TI - Uncommon postoperative temporomandibular joint complications. PMID- 7773867 TI - Effects of home bleaching on the tissues of the oral cavity. AB - Eight subjects used a 10 per cent carbamide peroxide (Opalesence) home bleaching system in a mouthguard for 14 nights. Their periodontal health was assessed by measuring gingival crevicular fluid flow with a Periotron 6000, and subjects were given a questionnaire to assess the effects of the bleaching system. There was no significant change in the gingival crevicular fluid flow, recession, bleeding index or plaque index of any patient during the treatment phase. All treated teeth were lightened, and mild transient tooth sensitivity was common to all participants. One subject experienced internal tooth discoloration, possibly due to marginal leakage around an amalgam restoration. PMID- 7773868 TI - Dental amalgam: scientific consensus and CDA policy. PMID- 7773869 TI - Papillon-Lefevre syndrome associated early onset periodontitis: a review and case study. AB - A case of Papillon-Lefevre syndrome that has been managed successfully for six years is reported. Papillon-Lefevre syndrome is a rare form of early onset periodontitis that occurs at a rate of 1-3 per million. Diagnostic features include palmar-plantar hyperkeratosis and rapid periodontal destruction. Although the etiology of this syndrome is unknown, current theories on the nature of the underlying defect fall into three main categories: anatomical, bacterial and host response. Historically, Papillon-Lefevre syndrome was thought to lead to the inevitable loss of both the primary and permanent dentitions. However, a recently proposed treatment involving antibiotic coverage, extraction of the primary dentition and a period of edentulism has been shown to be effective in maintaining the permanent dentition. Since treatment may begin prior to the eruption of the permanent dentition, early recognition of Papillon-Lefevre syndrome is critical. Any young patient who exhibits palmar hyperkeratosis should be examined carefully for periodontal breakdown. Since the number of cases available for study is limited, referral of such individuals to University dental clinics may allow for a more specific analysis of immune or bacterial factors that may lead to a better understanding of this disease. PMID- 7773870 TI - Osteomyelitis of the jaws. AB - Osteomyelitis is described as an inflammation of bone and bone marrow that may develop in the jaws following a chronic odontogenic infection or for a variety of other reasons. This situation may be acute, sub-acute or chronic, resulting in a totally different clinical picture. PMID- 7773871 TI - MR demonstration of an anomalous muscle in a patient with coexistent carpal and ulnar tunnel syndrome. Case report and literature summary. AB - An aberrant muscle is demonstrated by magnetic resonance (MR) imaging in a patient presenting with focal wrist swelling and compression neuropathy of median and ulnar nerves following 4 months of carpentry work. The muscle originated from the palmaris longus tendon and ulnar antebrachial fascia at the lower half of the forearm as a single belly, then diverged medially from palmaris longus tendon and bifurcated. Both portions of the split muscle extended into the distal ulnar tunnel or Guyon's canal. One segment joined with the abductor digiti minimi muscle and the other with the flexor retinaculum. MR was able to clearly delineate this hypertrophied, symptomatic muscle anomaly. It may be helpful when mass effect is suspected in either tunnel, or in patients with atypical work related carpal tunnel syndrome with evidence of significant ulnar neuropathy for evaluation of underlying anomalous musculature. Normal MR images of the wrist are included for comparison and the literature is reviewed. PMID- 7773872 TI - Cat-scratch disease. Subtle vertebral bone marrow abnormalities demonstrated by MR imaging and radionuclide bone scan. AB - Cat-scratch disease (CSD) is a benign, self-limited cause of lymphadenitis occurring mainly in children and young adults. Its etiology is a delicate, small gram-negative pleomorphic bacillus. Less common manifestations of CSD are seen in 5% of patients and include Parinaud's oculoglandular syndrome (with enlargement of the preauricular nodes), parotid gland enlargement, encephalitis, radiculopathy, pneumonitis, erythema nodosum, thrombocytopenia, and lytic bone lesions. We describe a patient in whom magnetic resonance imaging initially detected subtle vertebral bone marrow abnormalities that correlated with the site of abnormality on a subsequent radionuclide bone scan. PMID- 7773873 TI - MR characteristics of low-flow facial vascular malformations in children and young adults. AB - The purpose of this report is to describe the magnetic resonance (MR) imaging characteristics of low-flow vascular malformations of the face. We studied six patients ranging in age from 1 month to 20 years old, with surgically proven or clinically certain low-flow vascular malformations of the face. T1-weighted MR images of five lesions showed homogeneous intermediate to low signal intensity, similar to the signal intensity of muscle. T1-weighted images of one lesion showed mild high signal intensity and image of another demonstrated fatty infiltration. After contrast administration, images of four lesions showed moderate to marked enhancement, three diffused and one patchy. On T2-weighted sequences, five lesions were heterogeneously of high signal and one of low signal intensity. Three lesions exhibited low-signal septa, and two revealed low-signal vascular flow voids on both types of sequences. Satellite nodules were present in three instances. Low-flow vascular malformations involving the face in children and young adults have a heterogeneous and nonspecific appearance on MR images. They should be considered in the differential diagnosis of all facial masses presenting in children and young adults. Enhancement with contrast material is essential to localize the mass. PMID- 7773875 TI - Squamous cell carcinoma of the thymus with paraneoplastic hypercalcemia. AB - Primary thymic carcinoma is a rare neoplasm that in contradistinction to thymoma, is not supposed to be associated with a paraneoplastic syndrome. A 73-year-old man, with new onset of disorientation, was found to have an elevated serum calcium level as the cause. Computed tomography demonstrated a mediastinal mass, pericardial invasion, and metastases to the lung. Examination of a biopsy specimen revealed thymic squamous cell carcinoma. Thus, a paraneoplastic syndrome, in this case hypercalcemia, does not exclude primary carcinoma of the thymus. PMID- 7773874 TI - Cholelithoptysis: an unusual complication of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy is emerging as a preferred surgical method in the treatment of cholecystitis. Decreased morbidity and mortality rates make this an attractive alternative to conventional cholecystectomy. Recently, specific complications including bile duct transection, biloma formation, and liver lacerations have been reported. We report here, however, an unusual case of intraoperative spillage of stones into the intraperitoneal cavity. Subsequent erosion through the diaphragm resulted in expectoration of stones, or cholelithoptysis. PMID- 7773876 TI - Pleurocutaneous fistula as a complication of oleothorax. CT findings in three patients. AB - The purpose of this study was to highlight pleurocutaneous fistula, documented on computed tomography (CT) scans, as a complication of oleothorax. CT images of the chest were evaluated retrospectively in three patients with pleurocutaneous fistula complicating oleothorax. The images documented oleothorax rupture in all three, with only one patient (case 2) showing concomitant surrounding chest wall and axillary inflammatory reaction. Surgery performed on one patient (case 1) confirmed the CT findings. While CT is invaluable in the demonstration of complications of oleothorax, to our knowledge CT depiction of oleothorax has not been reported in the literature. This complication may be more common than described in earlier literature, with the advent of cross-sectional imaging. In the right clinical setting, CT findings of inflammation or edema surrounding the oleothorax rupture may warrant surgical intervention. PMID- 7773878 TI - CT of secondary neoplasms. Unusual structural features--a pictorial essay. AB - The newer anticancer therapies, the routine employment of cross-sectional imaging modalities for staging and follow-up, and the increased survival rate of patients with neoplastic lesions have markedly widened the range of pathological and imaging features of secondary neoplasms. Moreover, the changes occurring in morphological and structural aspects of metastases may be the direct effect of the improved therapeutic tools, and in turn may offer revealing clues to the clinician regarding the outcome of therapy itself. The scope of this essay is to show the atypical computed tomographic (CT) aspects of a series of metastatic lesions. We selected the lesions on the basis of their unusual structural features, such as calcification; hemorrhage; superinfection; pseudocystic, cystic, and lipoid appearance; and hypervascularity. A highly detailed assessment of such changes is nowadays possible and appears mandatory. PMID- 7773879 TI - A 24-year-old man with diplopia and frontal headache. PMID- 7773880 TI - Radiological evaluation of the craniocervical junction in bone dysplasias and other related syndromes. AB - The craniocervical junction, a vital but anatomically complex region, presents additional interpretative challenges in patients with skeletal dysplasias and other syndromes involving the musculoskeletal apparatus. Our objective was to review the radiological evaluation used in such conditions; to do so, we identified retrospectively all of the occipitocervical studies done during the last 3 years at our institution on patients with skeletal dysplasias and related syndromes. The 28 cases thus found were reviewed and the different diagnostic modalities identified; the diagnostic findings were summarized and classified into osseous and soft tissue abnormalities. The standard criteria for cervical instability and cord compression were compared with measurements reported in our selected cases. The lateral radiograph of the cervical spine was the first diagnostic test, followed by additional flexion-extension views and sagittal spin echo magnetic resonance imaging; no conclusive diagnostic criteria for occipitoatlantal instability in children with bone dysplasias were identified. PMID- 7773877 TI - Emphysematous gastritis in an immunocompromised host. AB - Emphysematous gastritis is a rare, often lethal condition of gastric mural inflammation and gaseous dissection. Infection with gas-forming organisms is the most frequently cited cause. In all previously reported patients, the clinical presentation was dramatic. We report on an immunocompromised host who had a surprisingly subtle clinical presentation. PMID- 7773881 TI - Hypoplasia of the right hepatic lobe with ectopy of the gallbladder. AB - Two cases of hypoplasia of the right hepatic lobe with gallbladder ectopy, which were diagnosed by computed tomography, are reported here. In each patient, the left hepatic lobe was enlarged. The gallbladder was located in the inferior portion of the liver in one patient and immediately below the right hemidiaphragm in the other. No other anomalies complicated these two cases. It should be kept in mind that hepatic lobe anomalies may have associated ectopy of the gallbladder. PMID- 7773882 TI - Intrahepatic, extramedullary hematopoiesis mimicking hemangioma on technetium-99m red blood cell SPECT examination. AB - Cavernous hemangiomas are the most common lesion of the liver. Because of the risk of hemorrhage inherent in percutaneous biopsy of such lesions, noninterventional modalities (such as CT, ultrasound, MRI and Technetium-99m red blood cell imaging) have been utilized for differentiating them from other lesions. The sensitivities and specificities of these techniques vary greatly. Technetium-99m red blood cell imaging with planar and SPECT imaging has been shown to have an overall sensitivity of 89%, a specificity of 100%, and an overall accuracy of 92%. Despite its high accuracy, rare false positives have been reported with Technetium-99m red blood cell imaging with SPECT. Review of the literature indicates four cases of hepatocellular carcinoma, one case of hepatic angiosarcoma, and one case of hepatic metastases from colorectal carcinoma as having an appearance identical to hemangioma with this modality. We present an additional false positive of a focal region of intrahepatic extramedullary hematopoiesis in a patient with Gaucher's disease as having an appearance on Technetium-99m red blood cell imaging with SPECT identical to that of hemangioma. PMID- 7773883 TI - Sacral insufficiency fractures. Spectrum of radiological features. AB - Clinical and radiological features of 22 Chinese patients with sacral insufficiency fractures were reviewed. Twenty-one were postmenopausal women. Other risk factors were external pelvic radiotherapy (eight) and total hip replacement (two). Severe low back pain was the most common presenting complaint. Fractures initially were demonstrated by bone scintigraphy in 21 and computed tomography (CT) in seven patients. Concomitant parasymphyseal and pubic rami fractures were detected in 17 and 10 patients, respectively. Follow-up assessment by CT and bone scintigraphy in five patients showed various stages of fracture healing. Recognition of the radiological patterns of this entity is emphasized. PMID- 7773884 TI - Medical newsletters: funding and interests should be stated. PMID- 7773885 TI - Controversy over use of pregnant mare's urine. PMID- 7773886 TI - Controversy over use of pregnant mare's urine. PMID- 7773887 TI - Controversy over use of pregnant mare's urine. PMID- 7773888 TI - Government waste confuses physician. PMID- 7773890 TI - Trauma kits on trains lack equipment. PMID- 7773889 TI - Gun control. PMID- 7773892 TI - Financial assistance needed for Tanzanian medical student. PMID- 7773891 TI - Physician-assisted death: suicide prevention and patient autonomy. PMID- 7773893 TI - A global network for medical journal editors. PMID- 7773895 TI - Factors associated with the decision of family physicians to provide intrapartum care. AB - OBJECTIVE: To investigate which characteristics and beliefs of family physicians determine their decision to provide intrapartum care. DESIGN: Confidential survey questionnaire mailed in spring 1993. SETTING: Alberta and Ontario. SUBJECTS: Random selection of 207 physicians who had graduated from medical school between 1953 and 1990 and were thought to be in family or general practice. Of 178 eligible physicians, usable replies were received from 104 (58.4%). OUTCOME MEASURES: Beliefs (measured on a 7-point Likert scale) about the relevance of 16 primary factors to the type of obstetric care provided; demographic, training and practice characteristics. RESULTS: The respondents who provided intrapartum care differed from those who did not in their beliefs about the availability of a local hospital suitable for intrapartum care (p < 0.001), their practice partners' views on the role of family physicians in providing obstetric care (p < 0.002), their own concept of the role of family physicians in providing obstetric care (p < 0.001) and women's views on the type of obstetric care they want (p < 0.002). They also differed, although less significantly, in their beliefs about the adequacy of their obstetric training before entering family practice (p < 0.04), the expected effects of providing obstetric care on their free time (p < 0.006), their fear of malpractice litigation (p < 0.028) and their perceived competence in performing practical obstetric procedures (p < 0.05). Logistic regression analysis revealed that certain secondary factors were particularly relevant to the respondents' provision of intrapartum care at present. These included the physician's perceived competence at managing postpartum maternal hemorrhage (odds ratio [OR] 48.90, 90% confidence interval [CI] 4.70 to 509), the belief that medical insurance premiums should not be affected by the type of obstetric care provided (OR 3.55, 90% CI 1.67 to 7.57]) and the number of practice partners who provided intrapartum care (OR 10.08, 90% CI 2.31 to 44.10). CONCLUSION: Several factors appear to influence family physicians in their decision to provide intrapartum care. This information will help to focus efforts to provide appropriate obstetric training for family practice residents and to retain involvement of family physicians in intrapartum care. PMID- 7773896 TI - Small-area variations in utilization of abortion services in Ontario from 1985 to 1992. AB - OBJECTIVE: To assess interregional differences in the utilization of abortion services in Ontario from 1985 to 1992. DESIGN: Retrospective analysis of provincial therapeutic abortion database. SETTING: All hospitals conducting abortions between 1985 and 1992 and all free-standing abortion clinics conducting abortions between 1990 and 1992. POPULATION: All women in Ontario aged 15 to 44 years who underwent a therapeutic abortion in Ontario during the study period. OUTCOME MEASURES: Utilization of abortion services by county and age-specific abortion rates by county of residence. RESULTS: From 1985 to 1989, when only hospital data were gathered, the mean therapeutic abortion rate increased by 11.2%. From 1990 to 1992, when data from hospitals and free-standing clinics were collected, the mean rate increased by 26.5%. Logistic regression analysis showed significant variation in the age-standardized abortion rates between counties in each study year (p < 0.0001). The counties with age-standardized rates below the 25th percentile had the highest proportions of women who sought abortion services outside their county of residence; in some of these counties no abortions were performed in local facilities. CONCLUSION: There are interregional variations in the utilization of abortion services in Ontario. These disparities raise questions about the accessibility of abortion services and need to be further investigated. PMID- 7773898 TI - Camphorated oil: still endangering the lives of Canadian children. AB - Camphor is a volatile, aromatic compound familiar to many people as a principal ingredient in topical home remedies for colds. It is highly toxic when ingested. Although camphorated oil in concentrations of 11% or greater is not longer sold in the United States, preparations containing concentrations of up to 20% are still sold over the counter in Canada. The authors describe two children who suffered severe poisoning after accidental ingestion of a small amount of camphorated oil. Both children exhibited generalized tonic-clonic seizures with subsequent respiratory depression. Treatment was symptomatic, consisting of seizure control and respiratory assistance. The authors argue that because camphorated oil is of questionable benefit and poses a danger to the public it should be removed from the market. PMID- 7773897 TI - Correlates of body mass index in the 1990 Ontario Health Survey. AB - OBJECTIVES: To determine the average body mass index (BMI) and the prevalence of overweight and obesity among people aged 20 to 64 years, to identify sociodemographic, lifestyle and health variables that correlate with overweight and obesity, and, through a comparison of the results with those from an earlier survey, to determine whether prevalence has changed over time. DESIGN: Cross sectional survey. SETTING: Ontario. PARTICIPANTS: The 1990 Ontario Health Survey surveyed 61,239 people representative of the Ontario population. The authors' analyses were restricted to those aged 20 to 64 years, excluding pregnant women. In the multivariate analyses they included only people with no missing values for any of the variables in the models (n = 26,306). OUTCOME MEASURES: BMI (weight in kilograms divided by height in metres squared) was used to measure healthy weight (BMI between 20 and 25), overweight (BMI greater than 25) and obesity (BMI greater than 27). RESULTS: The prevalence of obesity among men and women was 33.6% and 22.8% respectively (adjusted odds ratio [OR] 1.78, 95% confidence interval [CI] 1.63 to 1.95). There was a positive relation with age (adjusted OR 1.53 [95% CI 1.24 to 1.89] for age 25 to 29 years and 2.78 [95% CI 2.20 to 3.51] for age 50 to 54 years compared with age 20 to 24 years) and an inverse relation with education level (postsecondary education v. primary education: adjusted OR 0.65 [95% CI 0.54 to 0.79]). Analysis of birthplace showed that the prevalence of obesity was lowest among those born in Asia (compared with Canadian born: adjusted OR 0.36 [95% CI 0.27 to 0.47]). The prevalence was higher among former smokers than among those who had never smoked (adjusted OR 1.20 [95% CI 1.18 to 1.22]). People with more health problems and those who rated their health as fair or poor were more likely to be obese. The estimates of the prevalence of obesity were higher than those reported in the 1985 Health Promotion Survey for both sexes in all three age groups examined. CONCLUSIONS: These self-reported data indicate that overweight and obesity remain important health problems in Ontario, and the prevalence appears to be increasing. PMID- 7773899 TI - Statement on travellers and sexually transmitted diseases. PMID- 7773894 TI - Nutrient needs and feeding of premature infants. Nutrition Committee, Canadian Paediatric Society. AB - OBJECTIVE: To recommend appropriate intake of nutrients, food sources and feeding practices for premature infants. OPTIONS: Unfortified milk from the premature infant's own mother, fortified milk from the premature infant's own mother, formula designed for preterm infants and parenteral nutrition. OUTCOMES: From birth to 7 days, the minimum achievable goal is the provision of sufficient nutrients to prevent deficiencies and catabolism of nutrient substrate in premature infants; from 7 days to discharge from the neonatal intensive care unit, growth and nutrient retention at a rate similar to that which would have been achieved had the infant remained in utero; and for 1 year following discharge, nutrient intake to achieve catch-up growth. EVIDENCE: Few randomized clinical trials of feeding infants specific nutrients or of feeding choices have been conducted. On the basis of a MEDLINE search of the literature, committee members prepared reviews of the available information on each nutrient and feeding choice. The reviews were critically appraised by the committee. Recommendations were based on the consensus of the committee. VALUES: Whenever possible, the evidence was weighed in favour of randomized controlled trials. If such trials were unavailable, cohort studies were considered. If trials of either kind were unavailable, published data were reviewed and recommendations were based on consensus opinion. BENEFITS, HARMS AND COSTS: The advantages of feeding premature infants unfortified milk from their own mothers are psychologic benefits for the mother as well as anti-infective benefits and possibly improved intellectual development for the infant. However, unfortified milk from the infant's own mother is inadequate as a sole source of nutrients. The use of fortified milk from the mother results in faster growth as well as having the other benefits of mother's milk. When formulas designed for premature infants are given in adequate volumes, they provide an intake of nutrients that allows the infant to duplicate intrauterine growth without undue metabolic stress. RECOMMENDATIONS: The preferred food for premature infants is fortified milk from the infant's own mother or alternatively, formula designed for premature infants. This recommendation applies to infants with birth weights of a minimum of 500 g to a maximum of 1800 to 2000 g, or with a gestational age at birth of a minimum of 24 weeks to a maximum of 34 to 38 weeks (until the infant is able to nurse effectively). VALIDATION: These guidelines are in line with, but not identical to, recent guidelines by the Committee on Nutrition of the American Academy of Pediatrics and the Committee on Nutrition of the Preterm Infant of the European Society of Paediatric Gastroenterology and Nutrition. SPONSOR: The preparation of these guidelines was sponsored and funded by the Canadian Paediatric Society. PMID- 7773900 TI - New AIDS-treatment manual in BC. PMID- 7773902 TI - Murder-suicide involving BC doctor raises troubling questions about euthanasia. AB - The deaths last September of a British Columbia physician and his wife have raised troubling questions about euthanasia and Alzheimer's disease. Police described the deaths of Dr. Tom Powell and his wife Dr. Lorraine Miles, a retired dentist, as a murder-suicide. Friends of the couple wonder if more lenient laws concerning euthanasia and assisted suicide might have saved Miles' life. PMID- 7773901 TI - The Dutch experience with euthanasia: lessons for Canada? AB - Anne Mullens used a recent fellowship provided by the Atkinson Foundation to take an in-depth look at euthanasia in the Netherlands. During her time in Holland, she discussed the issue with doctors who support and oppose euthanasia. She accompanied a doctor as he visited a patient who was dying of cancer and was beginning to consider the possibility of euthanasia. She talked to a nonphysician who is adamantly opposed to euthanasia and carries a card stating that. She visited a hospital in Amsterdam that has received requests from foreigners seeking euthansia. Mullens offers a comprehensive look at an issue that continues to provoke strong feelings among Canadian physicians and patients. PMID- 7773903 TI - The message will be in the patient's receipt as New Brunswick prepares high-tech information system. AB - An effort to make the public appreciate the real cost of medical services has led to the development of an extensive medical-information and billing system in New Brunswick that uses a personal-information card. Likened to a credit card with unlimited credit, each has a magnetic strip with essential personal information with which to feed a province-wide computer system that eventually will link medicare, patients, doctors, prescription-drug programs and hospitals. The province hopes to have a pilot project running by year's end and then to introduce the system region by region. PMID- 7773904 TI - Health care reform comes to Alberta: "we're making this up as we go along". AB - Alberta left physicians out in the cold when Premier Ralph Klein's government began to slash the province's health care budget. Frustrated and angered at being excluded from the restructuring of the province's health care system, physicians rallied in protest, and now have some input into the new regional health authorities, at least in Edmonton and Calgary. Still, some physicians who feel the restructuring is an uncontrolled social experiment have opted to leave for positions in the US. PMID- 7773905 TI - "Why don't I send you and your wife two plane tickets..."? AB - Dr. James Hickey, who completed his residency in family medicine last year, reflects on medical practice and the negative impact of practice restrictions. At the same time the restrictions are appearing, he notes, recruiters from south of the border are conducting an aggressive campaign to convince Canadian family physicians to move to the US. PMID- 7773906 TI - I had an office to manage and patients to see. AB - An elderly woman seeks a physician's help because she has trouble sleeping and her doctor won't prescribe any more sleeping pills. The physician refuses to help, assuming that she is simply double doctoring. In the process, several doctors learn a lesson. PMID- 7773907 TI - Circumcision no longer a "routine" surgical procedure. AB - Nonmedical circumcision can no longer be considered routine in a new era of children's rights and more careful scrutiny of the medical necessity of surgical procedures. Although the minor procedure has been practised for centuries, custom and cultural factors may have had greater influence on the incidence of circumcision than the prevalence of problems such as penile cancer and urinary tract infection that it was thought to prevent. PMID- 7773909 TI - Homeopathy, other forms of alternative medicine sources of ongoing debate among physicians, patients. AB - Amy Rosen is the 1994 winner of the Amy Chouinard Memorial Essay Contest. Named in memory of longtime CMAJ and Canadian Journal of Surgery contributor Amy Chouinard, the competition is intended to stimulate interest in medical and health-related writing among journalism students. The winning essay examines the growing public interest in homeopathic medicine and physicians' opinions of the trend. PMID- 7773908 TI - The privatization of Canadian health care is moving into high gear. AB - The future of Canada's public health care system has been the source of much debate in the past year. Several signs, ranging from laser-surgery clinics in Ontario to the possible opening of a new private hospital in Toronto, indicate that the trend toward privatization is growing. Dr. Hugh Scully, former chair of a CMA working group that looked at the issue, expects the trend toward privatization to continue because "it simply isn't the case that the coverage people have come to expect will continue to be provided through the public purse." Dr. Jeffery Machat, a laser-surgery specialist from Windsor, Ont., thinks privatization brings needed investment to Canada's health care system. PMID- 7773910 TI - Looming public-service layoffs causing stress, other problems, Ottawa MDs report. AB - The federal government's attempts to curtail its deficit are going to cause thousands of layoffs in the Ottawa region, where the government is the main employer. The fear of being laid off is causing a great deal of stress among civil servants, and the signs of stress are being seen by the area's physicians. "We are seeing aggravated symptoms in people who have pre-existing psychiatric conditions," said Dr. Marvin Lange of the Royal Ottawa Hospital. "We are also seeing the emergence of new psychiatric symptoms in people who might not ordinarily have had them." PMID- 7773911 TI - Selection of students for veterinary medicine. PMID- 7773912 TI - Animals not abused by receiving somatotropin. PMID- 7773913 TI - Bovine somatotropin not abusive to cows. PMID- 7773914 TI - An ethicist's commentary of the case of a veterinarian utilizing homeopathic therapy. PMID- 7773915 TI - Therapy of gastrointestinal ulcers. PMID- 7773916 TI - Porcine colonic spirochetosis: a retrospective study of eleven cases. AB - This retrospective study of porcine colonic spirochetosis was done in order to characterize the clinical signs, the macroscopical and microscopical changes, and the bacteriological results of cases observed in Quebec. Necropsy records of all cases of colitis were reviewed. Eleven cases with filamentous bacteria colonizing the colonic epithelium were selected. This condition was only observed in weaned piglets, and was associated with mild persistent diarrhea and growth retardation. Macroscopic changes were generally limited to the presence of soft to liquid colonic contents. Adherence of filamentous helicoidal bacteria to the apical surface of the colonic epithelium and mild diffuse infiltration of the colonic lamina propria by mononuclear cells were the main histological findings. Weakly beta-hemolytic spirochetes were isolated in 6 cases. This condition seems to be underestimated for various reasons, and it is possible that some cases diagnosed as nonspecific colitis or superficial colitis, in fact, represent later stages of porcine colonic spirochetosis. PMID- 7773917 TI - The ecology of anthrax spores: tough but not invincible. AB - Bacillus anthracis is the causative agent of anthrax, a serious and often fatal disease of wild and domestic animals. Central to the persistence of anthrax in an area is the ability of B. anthracis to form long-lasting, highly resistant spores. Understanding the ecology of anthrax spores is essential if one hopes to control epidemics. Studies on the ecology of anthrax have found a correlation between the disease and specific soil factors, such as alkaline pH, high moisture, and high organic content. Researchers initially suggested that these factors influenced vegetative anthrax bacilli. However, subsequent research has shown that vegetative cells of B. anthracis have very specific nutrient and physiological requirements and are unlikely to survive outside a host. Review of the properties of spores of B. anthracis and other Bacillus species suggests that the specific soil factors linked to epidemic areas reflect important environmental conditions that aid the anthrax spores in causing epidemics. Specifically, high levels of calcium in the soil may help to maintain spore vitality for prolonged periods, thereby increasing the chance of spores encountering and infecting a new host. Cycles of runoff and evaporation may collect spores dispersed from previous epidemics into storage areas, thereby concentrating them. Uptake of large doses of viable spores from storage areas by susceptible animals, via altered feeding or breeding behavior, may then allow the bacterium to establish infection and cause a new epidemic. Literature search for this review was done by scanning the Life Sciences Collection 1982-1994 using the keywords "anthrax" and "calcium and spore." PMID- 7773918 TI - Immunoprophylaxis of bovine dermatophytosis. AB - The literature on immunoprophylaxis as control method for ringworm in cattle is reviewed. Scientific papers on immune response to dermatophyte antigens and vaccination against ringworm were obtained from personal files and computerized search in 4 relevant databases. Vaccines with antigens of Trichophyton verrucosum stimulate a humoral and cellular immune response. In animals vaccinated with inactivated vaccines, some protection is observed after challenge. However, the protective immunity is inadequate in most cases. Vaccination with live vaccines elicits an immune response that prevents the development of clinical disease. The protective immunity is based mainly on the cellular branch of the immune system. The efficacy and safety of live dermatophyte vaccines have been demonstrated in both challenge experiments and field trials from different countries. Effective control of ringworm in cattle has been achieved in regions implementing systematic vaccination. PMID- 7773919 TI - An outbreak of border disease in a sheep flock. PMID- 7773920 TI - Bovine spongiform encephalopathy in a Holstein cow born in the United Kingdom during September 1989. PMID- 7773921 TI - Arthrodesis of the scapulohumeral joint in a horse. PMID- 7773922 TI - Personnel points. PMID- 7773923 TI - Distribution of Streptococcus suis capsular types in 1994. PMID- 7773924 TI - [Cardiac dilatation in adult rabbits without evidence of relationship to the observed pathology]. PMID- 7773925 TI - Eastern equine encephalitis in horses in Ontario in 1994. PMID- 7773926 TI - [Presumed drug adverse reactions reported to the Bureau of Veterinary Drugs]. PMID- 7773927 TI - Joining a board of directors? Know your responsibilities. PMID- 7773928 TI - Serum anti-Helicobacter pylori antibody and gastric carcinoma among young adults. Research Group on Prevention of Gastric Carcinoma among Young Adults. AB - BACKGROUND: Helicobacter pylori is recognized as one of the possible causes of gastric carcinoma. There have been few studies on the relationship between H. pylori and gastric carcinoma in patients younger than 40 years. METHODS: Data and sera were collected from the cases (105 hospitalized patients younger than 40 years with gastric carcinoma from 9 hospitals in the Kanto-Shin-Etsu Area in Japan) and controls (102 hospitalized control subjects and 101 screening control subjects) whose sex and age (within 4 years) were matched. The serum anti-H. pylori immunoglobulin G antibody was measured, and the odds ratio (OR) for the association between seropositivity and gastric carcinoma was calculated. RESULTS: The OR (95% confidence interval) was 13.3 (5.3-35.6). For women, the OR was 32.8, whereas for men it was 6.8. The OR for patients with early gastric carcinoma was 20.8, and for patients with advanced disease, it was 10.8. The OR for intestinal type carcinoma was 18.0, and for diffuse-type carcinoma, it was 12.8. The OR for proximal carcinoma was 11.3, and for distal carcinoma it was 14.8. CONCLUSION: The OR for these young subjects was considerably larger than that for the older subjects in previously published studies. Among those younger than 40 years of age, early stage carcinoma has a stronger association with H. pylori than advanced carcinoma, and intestinal- and diffuse-type carcinomas have an association with H. pylori. PMID- 7773929 TI - Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases. AB - BACKGROUND: The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined. METHODS: The authors investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a sensitive polymerase chain reaction (PCR)-based method in 140 samples and correlated the findings with various clinicopathologic characteristics of the patients. RESULTS: The overall frequency of K-ras codon 12 point mutations in stomach cancer was 7.9% (11/140). DNA sequencing of nine cases with K-ras codon 12 point mutations identified seven cases with a single-base substitution of GGT to AGT (glycine to serine) and two with single-base substitution of GGT to AGT (aspartic acid). Tumors located in the upper third of the stomach had a significantly higher frequency of K-ras codon 12 mutations (3/8, 37.5%) compared with tumors located in the middle (4/29, 13.8%) or lower (3/99, 3.0%) thirds of the stomach (P = 0.001). No significant difference was observed in the frequency of K-ras codon 12 mutations in terms of other various clinicopathologic characteristics including tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly different between patients with stomach cancer with or without K-ras codon 12 mutation. Among eight patients with stomach cancer located in the upper part of the stomach, none of the three patients with K-ras gene-mutated tumors died versus four of five with tumors without K-ras gene mutations (P = 0.064). CONCLUSIONS: K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlation between K-ras mutations and vertical tumor location in the stomach, suggesting that different mechanisms may play a role in the pathogenesis of stomach cancer according to the location of tumors in the stomach. PMID- 7773930 TI - Localization of oncofetal and normal fibronectin in colorectal cancer. Correlation with histologic grade, liver metastasis, and prognosis. AB - BACKGROUND: Expression of oncofetal fibronectin (oncFN) and normal fibronectin (norFN) in colorectal cancer specimens was examined to investigate the correlation between fibronectin localization and histologic grade, liver metastasis, and prognosis. METHODS: Immunohistochemical staining of oncFN and norFN was performed on 99 primary lesions and 12 liver metastases of colorectal cancer. The expression of norFN and oncFN was evaluated by grading the intensity of staining as negative, positive, or strongly positive. RESULTS: Positive staining for oncFN correlated positively with increasing stage. The rate of strongly positive staining for oncFN was 53% for primary lesions with liver metastasis, significantly higher than the oncFN-positive rate of 13% for metastasis free cases (P < 0.05). Liver lesions had an oncFN-positive rate of 92%. The postoperative 5-year survival rate for 51 cases classified as Dukes Stage C was 77.8% for oncFN-negative cases, 36.5% for oncFN-positive cases, and 22.2% for oncFN-strongly positive cases; these rates were significantly different (P < 0.01). Conversely, there was no correlation between norFN and any clinical variable. CONCLUSION: Expression of oncFN is correlated with a poor prognosis of Dukes C colorectal cancer and may serve as a useful postoperative prognostic sign. PMID- 7773931 TI - The significance of intraoperative periportal lymph node metastasis identification in patients with colorectal carcinoma. AB - BACKGROUND: Nine patients who underwent Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH) procedures for colorectal cancer were found to have disease recurrence in the periportal area. This led to a retrospective study to determine whether periportal lymph node involvement could have been predicted intraoperatively for these patients. METHODS: One hundred twenty-four patients underwent second-look RIGS for recurrent colon and rectal cancer from 1986 to 1992. The monoclonal antibody (MAb) B72.3 was administered as the carrier agent to 87 patients and the CC49 second-generation MAb was administered to 37 patients. Both MAbs were radiolabeled with Iodine-125. RESULTS: Periportal lymph nodes with RIGS-positive tissue were found in 47 (38%) patients, hematoxylin and eosin-positive lymph nodes were found in 13 of 47, and in further immunohistochemical studies performed for 31 of the remaining 34 patients, positive lymph nodes were found in 8, resulting in an incidence of 48% (21/44). A critical review of the nine patients' charts who later presented with a tumor mass in the periportal area demonstrated intraoperative gamma-detecting probe counts in ratios three to five times that of the normal adjacent tissues in the periportal area at the time of first exploration. Probe-directed biopsy was reported to be histologically negative for tumor in these patients, and, thus, the surgeon proceeded assuming the periportal area to be negative. A retrospective study of the periportal lymph nodes of these patients using cytokeratin immunohistochemical analysis identified tumor in five (56%). CONCLUSIONS: These findings suggest that the RIGS system may be a valuable method of intraoperative prediction and detection of periportal lymph node metastasis. PMID- 7773932 TI - Expression of an endogenous galactose-binding lectin correlates with neoplastic progression in the colon. AB - BACKGROUND: Galectin-3 is an endogenous galactose-binding protein that is expressed in a wide range of normal and neoplastic tissues and is thought to be involved in cellular adhesion and growth regulation. Conflicting data have been reported regarding the expression of galectin-3 during carcinogenesis in the colon. METHODS: The authors studied the expression of galectin-3 in 153 tissue specimens, including 29 adenomas containing early cancer, 66 colon carcinomas of known Dukes' stage with available long term patient survival data, and 23 additional primary carcinomas with 35 associated metastases. An immunohistochemical scoring system was used that considers tumor heterogeneity and yields an integrated numeric score subject to statistical analysis. Genetically related colon cancer cells with different metastatic capabilities also were compared by Western blot analysis. RESULTS: Galectin-3 expression was significantly higher in high grade dysplasia and early invasive cancers compared with the adenomatous tissue from which they evolved (mean staining score, 2.33 vs. 1.15; P = 0.001). Galectin-3 expression in invasive cancers varied according to Dukes' stage, indicating a linear relationship with advancing stage (P = 0.008). Enhanced expression correlated with decreased long term patient survival (P = 0.021). Metastases expressed a higher level of galectin-3 compared with the primary cancers from which they evolved (P < 0.005) as did cultured cells of high metastatic capability compared with their counterparts with low metastatic potential. CONCLUSION: Galectin-3 expression in colonic mucosa is related to neoplastic transformation and metastatic progression. PMID- 7773933 TI - Small adenocarcinoma of the lung. Histologic characteristics and prognosis. AB - BACKGROUND: Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. METHOD: Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. RESULTS: Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. CONCLUSION: Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis. PMID- 7773934 TI - Therapy program for patients with advanced stages of chronic lymphocytic leukemia. Chlorambucil, splenectomy, and total lymph node irradiation. AB - BACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is variable. Staging systems define high risk groups, such as patients with Rai's Stage III and IV and Binet's stage C disease, as having a poor overall median survival. Most combination therapy programs have resulted in similar results. Chlorambucil remains the most commonly used drug, and new drugs, such as fludarabine, are promising. METHODS: Fifty-three patients with poor prognosis CLL (Stage III and IV) underwent chlorambucil treatment at a high intermittent dose. When Stage 0 was obtained, patients were considered responders and kept under surveillance. When the patients stopped responding after one or several courses of chlorambucil, further therapy was performed, including splenectomy (29 patients) and total lymph node irradiation (9 of the 29 splenectomized patients). RESULTS: The overall median survival was 60 months. Thrombocytopenia and anemia were resolved in 55% and 82% of the patients, respectively, after chlorambucil therapy and in 85% and 100%, respectively, after splenectomy. Complications occurred in 34% of the splenectomized population. Total lymph node irradiation was poorly tolerated in 66% of the patients. When this analysis was performed, 24 patients were classified as having Stage 0 disease with no disease progression for a mean of 21 months. CONCLUSIONS: Therapy programs allowing the selection of responders by the successive use of high intermittent dose chlorambucil and splenectomy may be beneficial in treating patients with advanced stage CLL. Because of its toxicity, total lymph node irradiation has no significant therapeutic effect. PMID- 7773935 TI - Use of immunohistochemical procedures in diagnosing angiosarcoma. Evaluation of 98 cases. AB - BACKGROUND: Differential diagnosis of angiosarcoma, predominantly showing a non- or poorly vasoformative proliferation from other types of sarcomas, poorly differentiated carcinomas, and amelanotic melanoma, is often problematic. METHODS: The use of antibodies directed against Factor VIII-related antigen (FVIIIRA), Ulex europaeus lectin type 1 (UEA-1), CD31, and vascular endothelial growth factor (VEGF) in the diagnosis of angiosarcoma was examined in 98 cases of autopsy-proven angiosarcoma diagnosed during 1974-1990 in a survey of 178 Japanese hospitals. Reactivity of angiosarcoma cells for epithelial membrane antigen, cytokeratin, and melanoma cell antigen (HMB45) also was examined. RESULTS: Histologic specimens were formed exclusively by vasoformative areas in 32 cases and combined vasoformative and varying extents of non- or poorly vasoformative areas in another 66 cases. In vasoformative areas, the proliferating cells showed a diffuse positive reaction in the cytoplasm and/or cell surface for anti-FVII-IRA in 82 (84%) of 98 cases, for anti-CD31 in 78 (80%), and for UEA-1 in 69 (70%). In non- or poorly vasoformative areas, the positivity rate for FVIIIRA, CD31, and UEA-1 was 29%, 62%, and 46%, respectively. A positive reaction was found for either one of three endothelial markers in the non- or poorly vasoformative areas of 57 cases (86%). Epithelial membrane antigen and anticytokeratin antibody were positive in 4 and 11 cases, respectively, in the vasoformative areas and in 3 and 14 cases, respectively, in non- or poorly vasoformative areas with a simultaneous positive reaction for either one of three endothelial cell markers. None of the proliferating cells showed a positive reactivity for HMB45. The positivity rates of the angiosarcoma cells for each marker were different according to the primary tumor sites. The angiosarcoma cells in non- or poorly vasoformative areas showed the lowest positivity rate for anti-FVIIIRA in the heart (9%) and for anti-CD31 in the extremities (17%) and the highest positivity rate for anticytokeratin in the trunk (60%). Ulex europaeus lectin type 1 had almost the same reactivity rate (30-56%) in every organ. Angiosarcoma cells in 13 (36%) of 36 biopsy specimens and 8 (14%) of 56 autopsy specimens were positive for the anti-VEGF antibody. CONCLUSION: These findings suggest that the combined use of endothelial cell markers including FVIIIRA, UEA 1, and CD31 is useful in the diagnosis of angiosarcoma, especially in cases exclusively with a non- or poorly vasoformative pattern. PMID- 7773936 TI - Contralateral axillary lymph node metastasis as the first evidence of locally recurrent breast carcinoma. AB - BACKGROUND: Carcinoma of the breast infrequently presents initially as axillary adenopathy. In such cases, after biopsy proves the presence of metastatic carcinoma, the primary tumor generally is assumed to be in the ipsilateral breast, despite negative mammographic findings and the lack of a clinically palpable breast mass. METHODS: The authors recently studied a case of a 50-year old woman in whom recurrent neuroendocrine carcinoma of the breast presented as a contralateral axillary lymph node metastasis. After mastectomy ipsilateral to the metastasis proved negative for tumor, a histologic comparison of the previous contralateral tumor with that in the lymph node was performed, followed by biopsy of the clinically and mammographically negative original lumpectomy site. RESULTS: Histologic and immunohistochemical studies proved that the original, metastatic, and locally recurrent tumors were identical, sharing unusual neuroendocrine features. The patient is currently disease free after chemotherapy. CONCLUSION: Contralateral mammary carcinoma should be considered in the workup of a patient who presents with evidence of an axillary lymph node metastasis. Locally recurrent breast carcinoma may be clinically and mammographically occult. Histologic review of prior biopsy material and comparison with current tissue is essential in proper patient management. PMID- 7773937 TI - Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus. AB - BACKGROUND: The incidence of vulvar intraepithelial neoplasia Grade III (VIN III) is increasing and is diagnosed at a younger age than previously. VIN III is often multifocal and frequently coexists with multicentric dysplastic lesions in the cervix and vagina. Warty-type VIN III more often has been found to contain human papillomavirus (HPV) DNA than basaloid-type VIN III: The authors performed HPV DNA polymerase chain reaction (PCR) analysis in 48 VIN III biopsies and reverse transcriptase (RT)-PCR in 8 HPV-16 DNA-positive multifocal VIN III biopsies to detect E6/E7 transcripts. METHODS: Human papillomavirus DNA detection and histologic analysis were performed on alternating slides of paraffin embedded biopsies. Polymerase chain reaction was performed with consensus primers, and HPV typing was performed by direct sequencing. Total RNA was isolated from frozen biopsies by centrifuging a guanidinium thiocyanate (GTC) lysate through a cesium chloride (CsCl) cushion. The RT reaction was performed using a 3' primer, located just downstream of the E7 stop codon, and the PCR reaction was performed using the same 3' primer and a 5' primer located just downstream of the E6 start codon. RESULTS: The mean age of the 48 patients was 37.7 years. Eighty-one percent had multifocal VIN III: Sixty-six percent had multicentric neoplasia. Forty-six percent of the biopsies were warty-type, 17% basaloid-type, 35% mixed-type and 2% differentiated-type. Ninety-two percent were HPV-positive and 83% contained HPV 16 DNA. Human papillomavirus DNA was more often present in multifocal VIN III lesions than in unifocal VIN III lesions and also more often in VIN III lesions coexisting with other dysplastic multicentric lesions than in unicentric VIN III lesions. Warty-type VIN III more often contained koilocytes than basaloid-type VIN III: A correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found. Both types of VIN III often coexist in one lesion. In all the RT-PCRs, a 593-base-pair fragment was detected, corresponding to the expected length of the major E6*-E7 mRNA. CONCLUSIONS: The observed high prevalence of transcriptionally active HPV DNA associated with multifocal and multicentric dysplasia suggests a role of HPV in the pathogenesis of these lesions. A positive correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found. PMID- 7773938 TI - Extracapsular growth of lymph node metastases in squamous cell carcinoma of the vulva. The impact on recurrence and survival. AB - BACKGROUND: Patients with squamous cell carcinoma of the vulva who present with multiple positive groin lymph nodes have poor survival. Growth of cancer through the capsule of the groin lymph nodes recently has been identified as an important prognostic factor for survival in that patient group. The objective of this study was to determine the influence of several clinicopathologic parameters on the pattern of recurrence and survival. METHODS: A review of 71 patients with squamous cell carcinoma of the vulva and positive lymph nodes was performed to assess the independent prognostic value of a number of variables for survival. Variables analyzed included tumor size, stage, number of positive lymph nodes, extracapsular growth of lymph node metastasis, the greatest dimension of tumor in the lymph nodes, the percentage of replacement of the lymph nodes by tumor, clinical lymph node status, and laterality of positive lymph nodes. RESULTS: Using the Mantel-Cox test, extracapsular growth of lymph node metastases (P = 0.00), two or more positive lymph nodes (P = 0.02), and greater than 50% replacement of lymph nodes by tumor (P = 0.03) were predictors of poor survival. No difference was found between the groups with two positive lymph nodes and those with three or more. Extracapsular growth of lymph node metastases was the most significant independent predictor for survival. Distant metastases occurred in 7 of 15 patients (48%) who had a combination of extranodal spread, lymph node replacement greater than 50%, and three or more positive lymph nodes. CONCLUSION: Extracapsular growth of lymph node metastases in the groin is the most important predictor for poor survival in patients with squamous cell carcinoma of the vulva. Because of the predominant distant failure pattern in a subgroup of patients who have a combination of extranodal spread, multiple positive lymph nodes, and lymph nodes replaced by tumor greater than 50%, a future study of the effectiveness of systemic therapy for vulvar cancer must include these patients. PMID- 7773939 TI - c-erbB-2 and p53 expression in fallopian tube carcinoma. AB - BACKGROUND: Carcinoma of the fallopian tube is a rare gynecologic malignancy. Its histologic appearance and patterns of spread are similar to those of epithelial ovarian cancer. Alterations in the gene products of c-erbB-2 (HER-2/neu) and p53 are found commonly in ovarian tumors and may have prognostic relevance. The authors sought to determine whether tubal cancers are biologically similar to ovarian cancer with respect to the expression of these two molecular markers. METHODS: A cohort of 43 patients with fallopian tube cancer was studied. Immunohistochemical staining for c-erbB-2 and p53 was performed on pretreatment tissue blocks. Clinical information was available for all patients, with a median follow-up of 9 years. Clinicopathologic correlations were made. RESULTS: Nine patients had Stage I disease, 11 had Stage II disease, 18 had Stage III disease, and 5 had Stage IV disease, with a median survival was 65 months. c-erbB-2 overexpression was found in 11 cases (25.6%), and p53 positivity was noted in 26 cases (60.5%). Log rank survival curves showed no association between staining for c-erbB-2 or p53 expression and clinical outcome. A multivariate analysis identified patient age older than 65 years (P = 0.05) and Stage III or IV disease (P = 0.0065) as the only variables that predicted poor outcome. CONCLUSIONS: Fallopian tube cancers are similar to ovarian cancer with respect to the proportion of tumors with abnormal expression of c-erbB-2 and p53. The authors could not demonstrate that these two molecular markers had prognostic relevance in this disease, but the size of their cohort was limited. However, the potential prognostic relevance of c-erbB-2 and p53 expression in tubal cancers should be pursued in a larger cohort. PMID- 7773940 TI - Cost and risk benefit in the management of clinical stage II nonseminomatous testicular tumors. AB - BACKGROUND: Two similarly effective treatment options exist for managing clinical low volume Stage II nonseminomatous germ cell testis tumors (NSGCT). Primary retroperitoneal lymph node dissection (RPLND) (with immediate adjuvant chemotherapy or chemotherapy at relapse) and primary chemotherapy have resulted in similar survival rates in large series. Because the chance for cure is similar with either approach, the cost and morbidity of therapy should be considered important discriminating factors in deciding which option to pursue for an individual patient. The purpose of this study was to undertake a cost/benefit and risk/benefit analysis of these two options using data and costs from the Indiana University experience. METHODS: The overall direct costs for 100 patients undergoing primary RPLND were compared with the total direct costs of 100 patients receiving primary chemotherapy for low volume Stage II disease, including the costs of adjuvant chemotherapy, salvage chemotherapy in relapsing patients, and routine follow-up for a 5-year period. In addition, the two treatment options were analyzed relative to survival, late relapse, acute and chronic toxicity, (including fertility), and perioperative morbidity. RESULTS: In this analysis, the overall 5-year costs of RPLND were significantly less than the costs of primary chemotherapy. The two options did not differ significantly in terms of survival or quality of life. Patients receiving RPLND were found to have an advantage also in terms of fertility, toxicity, and late relapse. CONCLUSIONS: Treatment decisions for patients with clinical low volume Stage II NSGCT may be based on cost/benefit and risk/benefit considerations, including relative toxicity, long term cure rate, and individual patient preference. Patient compliance with follow-up, the specific expertise of the physicians, and the availability of specialized therapeutic care ultimately may influence such decisions. PMID- 7773941 TI - The in vitro motility of human gliomas increases with increasing grade of malignancy. AB - BACKGROUND: Malignant gliomas are a highly invasive disease with a dismal prognosis despite aggressive therapeutic interventions. METHODS: The authors tested the hypothesis that increasing in vitro motility of human glial tumors correlates with increasing grade of malignancy. A radial dish assay was used to quantitatively assess the brain tumor cell motility of 14 low passage cell lines derived from human glial tumors of varied malignancy, and 3 cell lines derived from human glia. The egress of cells from a central region of high tumor cell density to a region of lower tumor cell density was determined at various time points. A motility coefficient (MC), the slope of distance traveled against time, was generated by simple linear regression analysis. RESULTS: The MC increased with the increased histologic grade of malignancy. Generation of a t-statistic was used to determine the significance of differences in motility among 5 histopathologic groups: 10 glioblastoma (World Health Organization Grade IV) cell lines (mean MC, 0.00396), 2 mixed anaplastic oligoastrocytoma (Grade III) cell lines (mean MC, 0.00382), 1 anaplastic astrocytoma (Grade III) cell line (mean MC, 0.00295), 1 Grade I glioma cell line (mean MC, 0.00206), and 3 human glial cell lines (mean MC, 0.00110). CONCLUSIONS: The radial dish assay provided a reproducible method for quantitatively assessing brain tumor cell motility. The higher MC observed with the malignant human glioma cell lines correlated with the tendency of these tumors to invade into adjacent brain tissue. The potential to inhibit glial tumor motility may provide an important therapeutic avenue in the future. PMID- 7773942 TI - Clinicopathologic features of primary and postirradiation cerebral gliosarcoma. AB - BACKGROUND: Gliosarcoma is an uncommon malignant brain tumor with mixed glial and mesenchymal elements. Experience is limited to case series, and pathologic data are disparate, leading to uncertainty about clinical features, management, and histogenesis. METHODS: A clinicopathologic review of 32 patients with survival analysis and immunohistochemical studies was performed including glial fibrillary acidic protein analysis, alpha-1-antitrypsin (alpha-1-AT) analysis, and smooth muscle actin (SMA) analysis. RESULTS: Twenty-five patients had primary gliosarcoma, whereas 7 developed gliosarcoma after irradiation for glioblastoma multiforme (GBM). Clinical features were similar to those of GBM. Most tumors were intraaxial and diffusely infiltrating by radiologic studies and at surgery. Median survival for primary gliosarcoma was 25 weeks overall, with patients who received irradiation surviving longer (46 vs. 13 weeks, P < 0.025). Gliosarcoma occurring after irradiation appeared hyperdense by computed tomography in five of seven cases, and median survival was 53 weeks. Primary gliosarcoma was a dimorphic tumor with malignant glial elements and features of malignant fibrous histiocytoma (MFH) or fibrosarcoma and one osteosarcoma. Smooth muscle actin labeled tumor vessels heavily, but in 15/25 primary cases, it extended to the surrounding spindle cells. The remaining cases appeared morphologically like MFH and tended to be positive for alpha-1-AT. Postirradiation gliosarcoma was fibrosarcomatous with positive SMA in 75% of the cases examined. CONCLUSIONS: Gliosarcoma behaves clinically like GBM, and survival may be improved by cranial irradiation of selected patients. Smooth muscle actin reactivity in sarcomatous areas suggests histogenesis in some tumors from the smooth muscle within GBM, whereas others may arise via different mechanisms including differentiation from a pluripotential precursor. Transformation of the smooth muscle within GBM may have therapeutic implications for antiangiogenesis agents. PMID- 7773943 TI - Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. AB - BACKGROUND: The authors assessed cerebrospinal fluid (CSF) flow in patients with carcinomatous meningitis using technetium-99m-DTPA (Tc-99) ventriculography to determine the frequency of flow abnormalities, their reversibility with treatment, and the implications for successful therapy and survival. METHODS: Technetium-99m-DTPA flow studies were performed in 31 patients after placement of Ommaya reservoirs (Baxter, McGaw Park, IL). Two millicuries of Tc-99 were injected into the reservoir. Planar images of the head and entire spine were obtained after 10 and 30 minutes and after 1, 4, 6, and 24 hours. Follow-up studies were performed for 12 patients whose initial studies were abnormal or who developed complications of therapy. RESULTS: In 19 of the 31 patients (61%), ventricular-outlet, spinal, or convexity blocks were identified. In 11 of these 19 patients, focal radiotherapy to the site of the block restored normal flow. Survival among patients with initially normal, abnormal but correctable, and abnormal but uncorrectable CSF flow differed significantly (6.9, 13.0, and 0.7 months respectively; P < 0.001). Some patients who were treated intrathecally despite abnormal CSF flow experienced drug-related toxicity. CONCLUSIONS: Cerebrospinal fluid-flow blocks are common in patients with carcinomatous meningitis and may occur at the skull base, in the spinal canal, and over the convexities. These flow abnormalities often can be corrected with appropriately directed radiotherapy. If untreated, CSF tumor progression (protected site effect), neurotoxicity (high concentration effect), and systemic toxicity (reservoir effect) can occur, resulting in shortened survival and treatment related morbidity. Therefore, intrathecal chemotherapy should be preceded by a radionuclide flow study and should be delayed if abnormal flow is documented until appropriate radiotherapy reestablishes normal flow. PMID- 7773944 TI - Phase I study of phenylacetate administered twice daily to patients with cancer. AB - BACKGROUND: The growth-inhibiting and differentiating effects of sodium phenylacetate against hematopoietic and solid tumor cell lines has aroused clinical interest in its use as an anticancer drug. In an earlier Phase I trial of phenylacetate aimed at maintaining serum drug concentrations in the range that proved active in vitro (> 250 micrograms/ml) for 2 consecutive weeks, infusion rates approached the maximum velocity of drug elimination and commonly resulted in drug accumulation and reversible dose-limiting neurologic toxicity. In this study, the authors described the nonlinear pharmacokinetics, metabolism, toxicity, and clinical activity of phenylacetate. METHODS: The treatment regimen of this Phase I study was designed to expose patients intermittently to drug concentrations exceeding 250 micrograms/ml and to allow time for drug elimination to occur between doses to minimize accumulation. Sodium phenylacetate was administered as a 1-hour infusion twice daily (8 a.m., 5 p.m.) at two dose levels of 125 and 150 mg/kg for a 2-week period. Therapy was repeated at 4-week intervals for patients who did not experience dose-limiting toxicity or disease progression. RESULTS: Eighteen patients (4 of whom previously were treated with phenylacetate by continuous intravenous infusion) received 27 cycles of therapy. Detailed pharmacokinetic studies for eight patients indicated that phenylacetate induced its own clearance by a factor of 27% in a 2-week period. Dose-limiting toxicity, consisting of reversible central nervous system depression, was observed for three patients at the second dose level. One patient with refractory malignant glioma had a partial response, and one with hormone-independent prostate cancer achieved a 50% decline in prostate specific antigen level, which was maintained for 1 month. CONCLUSIONS: Phenylacetate administered at a dose of 125 mg/kg twice daily for 2 consecutive weeks is well tolerated. High grade gliomas and advanced prostate cancer are reasonable targets for Phase II clinical trials. PMID- 7773945 TI - Cancer incidence of Hispanics and non-Hispanic whites in Cook County, Illinois. AB - BACKGROUND: Variations in cancer incidence and mortality rates between Hispanics and non-Hispanic whites have been reported in several regions in the United States. This report describes the ethnic variation in selected cancer sites in Cook County, Illinois. METHODS: Cancer incidence, age-specific, and age standardized relative rates, and 95% confidence intervals were estimated among Hispanics and non-Hispanic whites in Cook County, Illinois, for 1986-1987. Hispanics were identified using surnames and maiden names with the Generally Useful Ethnic Search System (GUESS). RESULTS: Rates of lung cancer in Hispanics were approximately half of those observed for non-Hispanic whites. Hispanics also had lower rates of colon, breast, and bladder cancer. Hispanic females had rates of invasive cervical cancer that were approximately two times higher than those of non-Hispanic whites. CONCLUSIONS: These results are consistent with previous studies and suggest that Hispanics residing in the United States may retain some of the risk profile of those living in their home country. PMID- 7773946 TI - Socioeconomic variation in cancer survival in the southeastern Netherlands, 1980 1989. AB - BACKGROUND: The survival rates of patients with cancer by socioeconomic status (SES) has never been investigated in the Netherlands, a country characterized by good general access to health care services. The association between socioeconomic status and survival from cancer of the lung (n = 4591), breast (n = 3928), colorectum (n = 3558), prostate (n = 1484), and stomach (n = 1455) was studied, and the impact of some prognostic factors (stage at diagnosis, histologic type, and treatment) on this association was assessed. METHODS: Subjects were patients who were diagnosed from 1980 to 1989 and included in the population-based Eindhoven Cancer Registry in the Southeastern Netherlands. The patients were classified by socioeconomic status based on their postal code of residence at the time of diagnosis (3 or 5 categories). The follow-up ended July 1, 1991, at which time relative survival rates and hazard ratios were calculated. RESULTS: A more favorable relative survival for patients living in high SES areas was found for those with cancer of the lung, breast, colorectum, and prostate, whereas for those with stomach cancer, lower survival was found for patients living in high SES areas. For cancer of the lung, colorectum, and prostate, the socioeconomic variation in survival could not be explained by the distribution of the prognostic factors stage, histologic type, and treatment. For patients with breast and stomach cancer, the socioeconomic variation in survival could be ascribed mainly to differences in the percentage of patients diagnosed with a metastasis. CONCLUSIONS: Socioeconomic variation in survival from a number of common cancer sites exists in the Netherlands, despite the fairly equal access to health care services for different socioeconomic groups. Most of the variation could not be explained by the differential distribution of stage, histologic type, and treatment across SES categories. PMID- 7773947 TI - Rheumatic manifestations of occult cancer. AB - BACKGROUND: The frequency with which rheumatic disorders occur when malignant neoplasms first present is unknown, and the significance of rheumatic conditions as cancer markers is unappreciated. METHODS: Patients admitted to a medical ward of a general hospital (Bnai Zion Medical Center, Haifa, Israel) during a 10-year period were surveyed. The frequency of the diagnostic evaluation of rheumatic disorders resulting in uncovering occult neoplasia at the time of index hospitalization and during the 2-year follow-up period was assessed. RESULTS: The incidence of occult cancer among patients admitted to a general medical ward with previously unclarified rheumatic disorders was 23.1%. Seventy-two percent of the group of patients with rheumatic diseases and occult cancer were male; 69% with rheumatic disease without cancer (control group) were female. The median age in the group with occult cancer was an average of 10 years older than the group without cancer, 67 versus 57 years (P < 0.001). Weight loss or anemia occurred in 52% of the group with occult cancer and in 37.3% of the control cases (not significant). Typically, there were no distinguishing features of the rheumatic syndromes suggesting the coexistence of cancer. In 19 of 25 cases, the malignancy was uncovered by routine examinations. In four instances, neoplasia was not immediately apparent but was identified in a specific search. In two cases, no search for malignancy initially was undertaken, and Hodgkin's lymphoma was diagnosed 6 and 12 months later. In 9 of 25 cases, long term remission of neoplasia was achieved by cancer therapy with improvement of rheumatic manifestations coinciding with regression. CONCLUSIONS: A significant number of patients who are referred to a general medical ward for evaluation of previously unclassified rheumatic disorders may be found to have a previously undetected malignancy. For most patients, the symptoms of cancer are found by routine physical and laboratory examinations. The importance of the association of rheumatic disorders and malignancy requires greater awareness, appreciation, and clinical study. PMID- 7773948 TI - A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin's lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. A Childrens Cancer Group study. AB - BACKGROUND: Recombinant human Interleukin-2 (IL-2) has been effective at inducing measurable antitumor responses in adults with renal cell carcinoma and melanoma. It also is being tested as adjuvant therapy for patients with acute myeloid leukemia after autologous bone marrow transplantation. METHODS: The authors tested IL-2 in a pediatric Phase II trial using a regimen that has antitumor effects in adults and was proven to be tolerated acceptably in a prior Phase I pediatric trial. Thirty-eight patients were entered into this study of whom 36 received IL-2 and were evaluable (20 with sarcoma, 9 with neuroblastoma, 5 with renal cell carcinoma, and 1 each with melanoma and lymphoma). RESULTS: Interleukin-2 dose modifications were based on tolerance and toxicity, such that 46% of these patients received a 50% increase in IL-2 dose during the second week, and 81% of those receiving the elevated dose continued receiving this dose level during the third week of treatment. A single patient with renal cell carcinoma had a complete response that was maintained; the remaining 35 patients did not show objective evidence of tumor response sufficient to qualify as either a complete response or a partial response. CONCLUSIONS: Absolute lymphocyte counts were indicative of the immunostimulatory effect of this IL-2 regimen as observed for adults, with a median 7.2-fold increase. Nevertheless, despite immune activation, a sufficient number of patients were evaluated, indicating that IL-2 does not have measurable antitumor effects in children with large refractory sarcomas or neuroblastomas, whereas one of five children with renal cell carcinoma had a complete response, consistent with the 10-20% response rate observed in adults. PMID- 7773949 TI - Etoposide, ifosfamide, and cisplatin therapy for refractory childhood solid tumors. Response and toxicity. AB - BACKGROUND: Etoposide, ifosfamide, and cisplatin (VIP) are each active in treating pediatric solid tumors, and this combination has been shown to be effective in treating adult germ cell tumors. Etoposide, ifosfamide, and cisplatin therapy was used to treat 11 patients, with ages ranging from 14 months to 22 years, with relapsed sarcoma, Wilm's tumor, and hepatoblastoma. METHODS: Etoposide, ifosfamide, and cisplatin therapy was administered daily for 3 days in doses of cisplatin 20 mg/m2 with mannitol 10 g/m2 for 1 hour, etoposide 100 mg/m2, and ifosfamide 1.5 g/m2 with MESNA 360 mg/m2 x 3 doses. A total of 65 courses (range, 3-10/patient) were administered, with 86% of the courses administered at full dose. Hematopoietic growth factors were not used. RESULTS: All 10 evaluable patients responded. Six patients had a complete response (CR) by computed tomographic or magnetic resonance imaging scan after one to three courses. The remaining four patients had a partial response (PR) (> 50% decrease in disease). One PR was converted to a CR by resection of the residual lesions. The major toxicity was myelosuppression. The median nadirs after full doses were as follows: leukocyte count of 900/mm3, absolute neutrophil count (ANC) of 156/mm3, platelet count of 61,000/mm3, and hemoglobin count of 8.6 g/dl; 75% of full dose courses led to an ANC of less than 500. Fever and neutropenia were observed after 8/55 (15%) full dose courses. Two episodes of bacteremia were noted, one with Staphylococcus epidermidis after full recovery of counts. The median time to hematologic recovery was 21 days (range, 14-29 days). No patient developed a decreased creatinine clearance level during therapy. Significant renal solute losses were observed in two patients, both of whom had been pretreated heavily with ifosfamide and had losses before VIP therapy. CONCLUSIONS: Etoposide, ifosfamide, and cisplatin appear to be active in treating childhood solid tumors. This therapy has predictable and tolerable myelotoxicity, and nephrotoxicity does not appear to be more severe than that observed after treatment with ifosfamide alone. PMID- 7773950 TI - Embryonal craniopharyngioma. Case report of the morphogenesis of a craniopharyngioma. AB - BACKGROUND: Ordinary craniopharyngiomas affecting sellar regions of children and preadolescents are composed of ameloblastomatous and/or squamous constituents. The authors encountered an autopsy case of a stillborn infant with a large craniopharyngioma with unusual manifestations. METHODS: The craniopharyngioma was analyzed using detailed histologic and immunohistochemical techniques. RESULTS: An autopsy revealed a large tumor arising from the pituitary gland with associated severe hydrocephalus. Histologically, the cells of the tumor showed features of ameloblastoma and organoid structures simulating tooth buds and adenohypophyseal primordia in the stage of organogenesis. Cells of the latter were shown to be immunoreactive for chromogranin A and six adenohypophyseal hormones. CONCLUSIONS: Because embryology of the adenohypophysis and the teeth indicated that all of the epithelia in this tumor emerged during the normal development of the stomodeum, it was believed that an "embryonal form of craniopharyngioma" would characterize this organoid neoplasm best. The possible morphogenesis of craniopharyngioma is also discussed. PMID- 7773951 TI - Characterization and chromosomal assignment of yeast artificial chromosomes containing human 3p13-p21-specific sequence tagged sites. AB - Human chromosomal region 3p12-p23 is proposed to harbor at least three tumor suppressor genes involved in the development of lung cancer, renal cell carcinoma, and other neoplasias. In order to identify one of these genes we defined sequence tagged sites (STSs) specific for 3p13-p24.2 by analyzing a chromosome 3p14 microdissection library. STSs were used for isolating yeast artificial chromosome (YAC) clones from the Centre d'Etude du Polymorphisme Humain (CEPH) YAC libraries. Thirty-eight YACs were assembled into a contig approximately 2.5 Mb in size spanning the t(3;8) and t(3;6) translocation breakpoints associated with hereditary renal cell carcinoma and hematologic malignancies, respectively. Chromosomal localization and chimeric status of 126 YACs was analyzed by fluorescence in situ hybridization (FISH). The order of 17 YACs determined by double-color FISH was in agreement with the STS-based arrangement of the YAC-contig. PMID- 7773952 TI - Appearance of isochromosome 18q can be associated with in vitro immortalization of human T lymphocytes. AB - T lymphocytes cultured from a skin biopsy specimen of a patient with atopic dermatitis developed isochromosome 18q concomitant to escape from replicative senescence. Furthermore, two T-cell lines established from patients with cutaneous T-cell lymphoma also developed isochromosome 18q during continuous growth. The results indicate that a pathway leading to immortalization of human T lymphocytes could involve genes located at chromosome 18. PMID- 7773953 TI - Cytogenetic study of a case of synchronous bilateral seminoma. AB - Cytogenetic analysis of a case of synchronous bilateral seminoma revealed, for each tumor, a chromosomal hypotetraploid mode with gain and loss of chromosomes and only one structural rearrangement, del(1p) and i(12p), which were secondary chromosomal events for the left and right tumors, respectively. This study allowed us to discriminate between a sole or independent origin for these two tumors. PMID- 7773954 TI - Clonal origin of Philadelphia chromosome negative cells with trisomy 8 appearing during the course of alpha-interferon therapy for Ph positive chronic myelocytic leukemia. AB - The transient appearance of a Philadelphia chromosome (Ph) negative clone with trisomy 8 was found in the bone marrow cells from a patient with Ph positive CML during the course of alpha-interferon (IFN) therapy. To determine whether this clone was derived from a Ph positive clone or from some other cell lineage, we performed molecular cytogenetic studies on bone marrow cells from the patient by fluorescence in situ hybridization (FISH). No fusion of BCR-ABL could be detected in cells with trisomy 8, clearly indicating that the Ph negative trisomy 8 clone was not derived from the Ph positive CML population. PMID- 7773955 TI - Translocation 11;14 in newly diagnosed chronic myelogenous leukemia. AB - In patients with chronic myelogenous leukemia (CML), the Philadelphia chromosome may be associated with a number of other cytogenetic lesions. However, t(11;14)(q13;q32), found mainly in B-cell lymphoproliferative disorders, has not been previously reported in Ph-positive CML. We describe a patient with hematologically typical chronic phase CML in whom both cytogenetic lesions were found at diagnosis. PMID- 7773956 TI - B-cell small lymphocytic lymphoma with circulating granular prolymphocytes and a novel trisomy 15 anomaly. AB - A 53-year-old man presented with cervical lymphadenopathy and massive splenomegaly. Peripheral blood examination showed many prolymphocytes with cytoplasmic azurophilic granules, giving an initial impression of large granular lymphocytosis. The lymph node biopsy and immunohistochemical study findings, however, were more compatible with a diagnosis of B-cell small lymphocytic lymphoma. The circulating prolymphocytes showed restricted kappa light chain expression similar to the lymphoid infiltrate in the lymph node. Karyotypic analysis revealed trisomy 15, a chromosomal abnormality that has rarely been described in small lymphocytic lymphoma or chronic lymphocytic leukemia. PMID- 7773957 TI - Translocation (9;22)(q22;q12). A recurrent chromosome abnormality in extraskeletal myxoid chondrosarcoma. AB - Cytogenetic analysis of a case of extraskeletal myxoid chondrosarcoma revealed a reciprocal translocation between 9q and 22q in almost all metaphases analyzed. Structural rearrangements involving 9q and 22q have been reported previously in three cases of extraskeletal myxoid chondrosarcoma. The breakpoints on chromosomes 9 and 22 in the present case were in regions 9q22-q31 and 22q11 q12.2, respectively. The same breakpoints were present in all three previously reported cases. Thus, this recently identified rearrangement of 9q and 22q may serve as a critical cytogenetic parameter for the diagnosis and classification of extraskeletal myxoid chondrosarcoma, as well as being a primary chromosomal event in the course of development of this rare malignancy. PMID- 7773958 TI - Translocation (5;6) associated with spontaneously remitting congenital leukemia. AB - We describe a newborn with acute monocytic leukemia who underwent spontaneous remission. Chromosomal analysis of this patient's leukemic blasts identified a translocation between 5q31 and 6q21. Chromosome 5 has been implicated in adult leukemogenesis but only rarely in childhood leukemia. Several hematopoietic growth factors and growth factor receptors have been mapped to the long arm of chromosome 5. This report discusses the possible role of these gene products in inducing leukemia in our index case. PMID- 7773960 TI - Cytogenetic analysis of short-term cultured squamous cell carcinomas of the lung. AB - Cytogenetic analysis of 122 primary squamous cell carcinomas of the lung revealed clonal abnormalities in 56 tumors. Karyotypes with simple numerical changes were found in 32 tumors: 45,X,-Y in 28, 47,XY,+7/45,X-Y, in two, 47,XY,+Y/45,X,-Y and 47,XY,+20/45,X,-Y in one tumor each. A super-numerary ring chromosome was the sole anomaly in two tumors. Complex structural changes were found in 22 tumors. The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (15 tumors), 3, 7, and 11 (10 tumors each), 5 and 6 (nine tumors each), and 2, 8, and 12 (eight tumors each). The bands and regions most often affected were 1p11-13 and 5cen (six tumors each), 11p11, 14p11-13, 15cen, and 17p11-12 (five tumors each), and 12p13 and 13cen (four tumors each). The only recurrent changes were the whole-arm rearrangements i(5)(p10) (five tumors) and i(6)(p10), der(9;15)(q10;q10), and der(13;15)(q10;q10) (two tumors each). The most prominent genomic imbalances were, apart from losses of the Y chromosome, losses from 1p, 3p, 5q, 6q, 8p, 13p, and 14p and gains from 1q and 5p. PMID- 7773959 TI - No association between HLA-DQ and -DR genotypes with nasopharyngeal carcinoma in southern Chinese. AB - The pathogenesis of nasopharyngeal carcinoma (NPC) is multifactorial. Associations have been reported between HLA and NPC. We studied the HLA-DR and DQ regions on the molecular level in 136 persons (51 NPC patients and 85 healthy controls) from southern China, a particularly high-prevalence area for NPC. Restriction fragment-length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha, and DQ beta regions of the subjects. Polymerase chain reaction (PCR) using sequence-specific primer (SSP) for DQ beta genes was also performed. By RFLP, no significant difference was observed with respect to DRB, DQA, and DQB genes. By PCR SSP typing, we confirmed that there was no significant difference between NPC patients and controls with respect to DQ beta alleles. Our study suggests that HLA-DQ and -DR genes are not associated with NPC in southern Chinese and there may be other gene loci that predispose them to have such a high prevalence of the disease. PMID- 7773961 TI - Correlations of chromosome abnormalities with histologic and immunologic characteristics in 49 patients from Akita, Japan with non-Hodgkin lymphoma. AB - We have analyzed the chromosomes of 49 non-Hodgkin lymphoma patients from an area of Japan that is nonendemic for adult T-cell leukemia/lymphoma. Clonal chromosome abnormalities were found in the majority (88%) of the specimens examined. The most characteristic structural abnormalities were: t(14;18)(q32;q21), t(3;22)(q27;q11), t(11;14)(q13;32), idic(18)(p11.2), and the combination del(1)(p13) and del(1)(q11). The t(14;18) were found in four of five follicular lymphomas and in one diffuse lymphoma. The breaks at 3q27 included seven translocations and an inv(3)(q12q27). A t(3;22) was found in three patients, all B-cell type, two of whom had kappa phenotype and one of whom was negative for the surface Ig. Fifteen of 49 cases had deletion of 6q. The common deleted region was found only in the segment distal to 6q21. These findings indicate the high percentage of t(14;18) in follicular lymphomas, which is unusual in Japan, and the high incidence of 3q27 translocations. PMID- 7773962 TI - Cytogenetic report of a male breast cancer. AB - The cytogenetic findings on G-banding in an infiltrating ductal breast carcinoma in a 69-year-old man are reported. The main abnormalities observed were trisomy of chromosomes 8 and 9 and structural rearrangement in the long arm of chromosome 17 (add(17)(q25)). Our results confirm the trisomy of chromosome 8 in the characterization of the subtype of ductal breast carcinomas and demonstrate that chromosome 17, which is frequently involved in female breast cancers, is also responsible for the development or progression of primary breast cancers in males. PMID- 7773963 TI - Renal cell carcinoma with translocation (X;1). Further evidence for a cytogenetically defined subtype. AB - A renal cell carcinoma from a 15-year-old male had a 49,Y,t(X;1)(p11.2;q21), +der(X)t(X;1) (p11.2;q21), +5, -16, +17, +18 karyotype. This is the third report of a translocation involving a breakpoint at Xp11.2 in a renal cell carcinoma in a child. A total of nine cases of renal cell carcinoma involving Xp11, including this case, have been reported. Of the eight cases for which there are genetics reports, all are male. Patients with renal cell carcinoma with abnormalities at Xp11 appear to be younger than renal cell carcinoma patients overall. PMID- 7773964 TI - RT/PCR detection of SIL-TAL-1 fusion mRNA in Chinese T-cell acute lymphoblastic leukemia (T-ALL). AB - The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell acute lymphoblastic leukemias (T-ALL), this gene is disrupted in its 5' portion by a site-specific 100-kg deletion and is fused with the 5' part of the SIL gene, to form SIL-TAL-1 chimeric gene. In this study, we established a "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique which allows detection of the SIL-TAL-1 transcriptional expression. A chimeric mRNA was observed in four of 17 T-ALL cases and has been shown to result from the fusion between the exon 1 of SIL and exon 3 of TAL. A sensitivity test showed that this RT/PCR procedure could detect one leukemic cell among 10(6) normal cells. A positive RT/PCR result was obtained in two cases during clinical remission, suggesting the presence of minimal residual disease (MRD). One patient developed clinical relapse 3 months after PCR positivity. Moreover, analysis of the Tald rearrangement by DNA-based PCR in four patients with SIL-TAL-1 fusion revealed the type A (Tald1) rearrangement in all cases. Sequence analysis demonstrated the presence of N region and non-random "P" nucleotide, as well as base deletions at the genomic SIL-TAL-1 joining site. These data indicate that detection of TAL-1 gene abnormality is important for diagnosis and monitoring of MRD in a subset of T-ALL. PMID- 7773965 TI - Characterization of a 14q+ marker chromosome in philadelphia chromosome positive acute lymphoblastic leukemia by DNA analysis and fluorescence in situ hybridization. AB - We report a case of precursor-B acute lymphoblastic leukemia (ALL) with the Philadelphia chromosome (Ph) and a 14q+ chromosome whose additional material was a part of the long arm of der(9)t(9;22). A minor population carrying the standard Ph translocation without the 14q+ was also observed at the first presentation. The translocation of the BCR gene from chromosome 22 to the subtelomeric region of the 14q+ was confirmed by fluorescence in situ hybridization (FISH) using a yeast artificial chromosome (YAC) clone containing the BCR gene. The breakpoint of chromosome 14 could not be determined exactly but probably was at 14q24 or 14q32 by conventional chromosome analysis. Nevertheless, FISH using a YAC clone containing the human immunoglobulin heavy chain (IgH) gene locus, Southern blot, and pulsed-field gel electrophoresis (PFGE) analyses with IgJH probe, and loss of heterozygosity analysis at the alpha 1-antitrypsin (AT) gene locus showed lack of involvement of the IgH gene in the 14q+ and more centromeric breakage than the alpha 1-AT locus at 14q32.1. Thus, the formation of the 14q+ seemed to be a secondary genetic event after the Ph translocation and presumably played a minor role in the pathogenesis of B-cell malignancy in this case. PMID- 7773966 TI - Concomitant partial tetrasomy 3q and trisomy 18 in Waldenstrom macroglobulinemia. AB - We report a 54-year-old female patient with Waldenstrom macroglobulinemia who shows concomitant partial tetrasomy 3q in the form of an additional isochromosome 3q, and trisomy 18. To our knowledge, isochromosome 3q has not been reported in chronic lymphoproliferative disorders. A review of the literature on karyotypic aberrations in Waldenstrom macroglobulinemia suggests that additional copies of the long arm of chromosome 3 and chromosome 18 may play a possible role in the pathogenesis of a subset of this disorder. PMID- 7773967 TI - Trisomy 8 in alveolar soft part sarcoma. AB - Cytogenetic studies were performed on an alveolar soft part sarcoma of a 6-year old boy. An extra chromosome 8 was present in 26 of 28 metaphases analyzed. PMID- 7773968 TI - Constitutional and acquired rearrangements of chromosome 7 in Wilms tumor. PMID- 7773969 TI - Deletion of both chromosome 7 homologues in leiomyoma. PMID- 7773970 TI - Timing of surgery in patients with infected spinal dermal sinuses: report of two cases. AB - In the past, if infection was present at the time a spinal dermal sinus was discovered, the sinus opening and cerebrospinal fluid were sterilized with a course of appropriate antibiotic therapy prior to the surgical intervention. The cases of two children with an infected spinal dermal sinus are reported here. One patient developed acute paraplegia during the initial stage of antibiotic therapy, and the second patient, who was admitted only with signs of fever and irritability, experienced after antibiotic therapy a complete myelographic blockade secondary to a large infected intradural dermoid tumor. The authors stress the importance of early neuroradiological and neurosurgical management of these lesions, even when an infection is present. PMID- 7773971 TI - Late thalamic atrophy in infarction of the middle cerebral artery territory in neonates. A prospective clinical and radiological study in four children. AB - We report four cases of progressive thalamic atrophy following ipsilateral cerebral infarction in the territory of the middle cerebral artery in neonates, with prospective radiological and clinical follow-up. This type of atrophy appears within 6 months after the onset of cerebral infarction. In the short term, this atrophy has no action on sensory and memory function and/or on sensory evoked potentials. This atrophy is not the result of secondary ischemic neuronal damage. Judging from several other experimental studies, thalamic atrophy may primarily result from retrograde degeneration. It would be interesting to observe the consequences of this atrophy on sensory and memory function over a long period. PMID- 7773972 TI - Pediatric cystic meningioma: report of three cases. AB - Three cases of pediatric cystic meningioma are reported. In a review of the literature the authors stress the importance and difficulty of accurate preoperative diagnosis. Cystic meningioma in pediatric patients differs from that in adults in the following respects: higher incidence, predilection for males, shorter clinical history, less specific neuroradiological diagnosis, frequent absence of a dural attachment, prevalence of Nauta type II cystic meningioma, and high incidence of the fibroblastic histotype. PMID- 7773973 TI - Calcified astrocytoma of the amygdalo-hippocampal region in children. AB - Three pediatric cases of temporal lobe seizure due to calcified glioma of amygdalo-hippocampal region are described. Computed tomography and magnetic resonance imaging showed dense calcification with no postcontrast enhancement in the amygdalo-hippocampal region. Positron emission tomography showed low oxygen metabolism, low glucose metabolism, hypermetabolism of amino acids, and low regional cerebral blood flow in the tumors. Single photon emission computed tomography showed a high accumulation of 201Tl chloride and 123I-isopropyl iodoamphetamine in one tumor, but otherwise low radioisotope uptake. These studies indicated low-grade malignancies. The patients were treated by partial tumor removal and radiotherapy. Histological examination of the tumor specimens showed astrocytoma with interstitial calcification. One patient died due to tumor recurrence, while the others are doing well with minimal seizure. We recommended temporal lobectomy in similar cases to achieve complete remission. PMID- 7773974 TI - Neurosurgical management of Walker-Warburg syndrome. AB - The Walker-Warburg syndrome (WWS) is a lethal complex of the central nervous system and the eyes. At present its cause is unknown, but clinical evidence strongly suggests that it is an autosomal-recessively inherited disorder. We report a series of nine children with WWS. The diagnosis was established by the detection of lissencephaly, hydrocephalus, and cerebellar malformation on computed tomography. All children exhibited profound psychomotor retardation and ocular abnormalities (in their anterior or posterior eye chambers). The existence of an occipital encephalocele in eight cases was the main diagnostic clue to WWS. Six patients were investigated for the presence for congenital muscular dystrophy, which was confirmed in only four of them. There were no patients with a cleft lip or palate. We studied the incidence of WWS in Spain and estimated it at 0.21 cases per 10,000 live-born children. In our series, WWS was prevalent in the Spanish gypsy population. Consanguinity was present in five of seven affected families. In a case of pregnancy with twins, one of the siblings was unaffected. Eight patients were treated with ventriculoperitoneal shunts and seven underwent encephalocele repair. Histological study of the excised encephaloceles demonstrated two different patterns. Interestingly, one of the infants showed coronal craniosynostosis. Finally, we include in the appendix, for completeness, a report of the case of the sibling of a WWS patient with acrania-exencephaly. PMID- 7773975 TI - SPECT and epilepsy with continuous spike waves during slow-wave sleep. AB - Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using 99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion. PMID- 7773976 TI - Residual spasticity after selective posterior rhizotomy. AB - The technique used in performing selective posterior rhizotomies to treat spastic cerebral palsy remains controversial. One hundred nine children who had undergone selective posterior rhizotomies were studied 6 months after their surgery. Their residual spasticity was correlated to the number of roots and whether or not abnormally responding roots were left, in order to validate the surgical technique used to treat spastic cerebral palsy at most neurosurgical centers in North America. The children were divided into three groups (group A: children who had their L2-S1 roots tested and selectively lesioned, n = 15; group B: children who had their L2-S2 roots tested and selectively lesioned, n = 62; group C: children who had their L2-S2 roots tested and whose lesioning was directed both by the response to the stimulation and mapping of the S1-S3 dorsal roots for afferent pudendal nerve activity, n = 32). Clinically significant residual spasticity was present in the gastrocnemius in 33% of the group A children, 11% of the group B children, and 6% of the group C children. We found that there was no significant increase in residual spasticity in the group C children when abnormally responding roots were not cut in order to preserve pudendal nerve activity. This study shows that the inclusion of the S2 roots decreases the amount of residual spasticity (P < 0.01). It also shows that leaving abnormally responding S2 roots to preserve pudendal nerve activity does not affect the incidence of postoperative spasticity (P > 0.1). PMID- 7773977 TI - Experiences with flow-regulated shunts (Orbis-Sigma valves) in cases of difficulty in managing hydrocephalus in children. AB - Due to an increasing number of shunt complications with conventional valves, we performed a study of 80 flow-regulated Orbis-Sigma valves implanted in 47 children who had had repeated complications with conventional valves and 33 children receiving their first shunt. The results were encouraging. During the first 5 years after implantation, the probability of absence of any kind of surgical intervention to the valve system was 57% and the probability satisfactory function of the valve itself was 70%. The most frequent complication was underdrainage of CSF, especially in children under the age of 1 year. No cases of CSF overdrainage occurred in this series. The Orbis-Sigma valve appears especially useful for patients unable to tolerate the anti-siphon device, and for patients over 1 year old receiving their first valve for hydrocephalus of non tumoral and non-haemorrhagic origin. PMID- 7773978 TI - Triventricular hydrocephalus: review of 71 cases evaluated at the Istituto Neurologico "C. Besta" Milan over the last 10 years. AB - The authors review 71 patients with triventricular hydrocephalus in whom a contrast-enhanced CT scan did not show any tumoral or vascular lesion that could have caused the hydrocephalus. The patients were subdivided into three age groups. The results of the neuroradiological examination, the surgical treatment, and the complications of the shunt procedure are analyzed, with special reference to the high number (13) of periaqueductal alterations of signal pattern found on MRI (interpreted as a "slow growing" neoplasm) and to the incidence and causes of shunt malfunction. PMID- 7773979 TI - Long-term follow-up in 233 patients with congenital hydrocephalus. AB - Data on 233 children with congenital hydrocephalus who were operated on in our department from 1964 to 1984 were analyzed. The study was started in January 1990 and was based on questionnaire followed by a psychological examination. Thirty two patients (13.7%) died during the follow-up period. The average number of operations during the observation period was 2.7; in 166 patients (= 71.2%) the shunt had to be revised at least once. The reason for revision was a mechanical problem in 79.4% and infection in 15.5%. The psychological evaluation in 115 patients showed a normal performance in 62.8%, while 29.8% had mild retardation, evident in speech impairment and/or impaired speech development, in memory and concentration, in poor intellectual performance and decreased performance in school. Severe retardation was seen in 7.4% of cases. Our results showed that the best outcome can be achieved with early shunt implantation. We did not, however, find any correlation between shunt revision rate and psychological results. PMID- 7773980 TI - Long-term results after ventriculo-atrial shunting in children. AB - A consecutive series of 120 patients with infantile hydrocephalus who were submitted to ventriculo-atrial shunting was studied. The average follow-up was 11 years. There was no operative mortality; 7 patients died during the follow-up period, but only in 1 case was the cause of death a consequence of the shunt procedure. The incidence rates of infection and slit ventricle syndrome were 4.2% and 1.8%, respectively. Shunt revision was performed on 253 occasions yielding a revision rate of 2.2 per patient. Of these 253 revisions 167 (66%) took the form of elective lengthening of the atrial catheter. The number of reoperations to adjust the length of the atrial catheter or to revise the distal end of the shunting system is a major disadvantage, which actually favors ventriculo peritoneal shunting as the primary procedure for the treatment of pediatric hydrocephalus. PMID- 7773981 TI - Long-term outcome in aqueductal stenosis. AB - In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections). PMID- 7773983 TI - Structural investigation on the carbohydrate backbone of the lipopolysaccharide from Klebsiella pneumoniae rough mutant R20/O1-. PMID- 7773982 TI - Malignant melanotic neuroectodermal tumor of infancy. AB - A 2-month-old boy underwent surgery for removal of a right temporal melanotic neuroectodermal tumor of infancy (MNTI). Histologically the tumor tissue showed signs of malignancy. The child was reexamined several times up to the age of 5 years. Neuroradiological evaluation showed no evidence of tumor recurrence or metastases. No resulting handicap was observed during neurological and psychological follow-up examination at the age of 5 years. Our findings confirm that surgical removal as the therapy of choice provides an excellent prognosis for this kind of tumor in spite of its histologically malignant appearance. PMID- 7773984 TI - Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-galactitol. AB - Described herein is an efficient method for the synthesis of the sixteen positional isomers of methylated and acetylated or benzoylated 1,5-anhydro-D galactitol. The compounds are generated simultaneously by partial methylation of 1,5-anhydro-D-galactitol and subsequent benzoylation, and the individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation and acetylation yielded the desired acetates. Reported herein are the 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tetra-O-methyl derivative. Also reported for the acetates and the tetra-O-methyl derivative are their linear temperature-programmed gas liquid chromatography retention indices on three different capillary columns. PMID- 7773985 TI - TLC-LSIMS of neoglycolipids of glycosaminoglycan disaccharides and of oxymercuration cleavage products of heparin fragments that contain unsaturated uronic acid. AB - Heparin and chondroitin sulfate disaccharides have been investigated by high performance (HP) TLC and liquid secondary-ion mass spectrometry (LSIMS) after conversion to neoglycolipid derivatives by reductive-amination with an aminolipid (dihexadecyl phosphatidylethanolamine, DHPE). Mobility on HPTLC was largely determined by the number of sulfate groups present, but was also influenced by the position of sulfate, monosaccharide composition and linkage. The mass spectra acquired directly from the TLC plate provided quasimolecular and fragment ions from which composition, including sulfate content, and sequence information was obtained at high sensitivity. Lipid DHPE conjugation and TLC-LSIMS were performed to analyse products of the oxymercuration reaction used to cleave unsaturated uronic acid (delta UA) residues from glycosaminoglycan (GAG) fragments produced by enzymatic degradation with glycan lyases. Previously the identification of the product from delta UA and the integrity of the remaining structures from oligosaccharides larger than disaccharide have not been made. Multiple and characteristic products of the cleaved delta UA were detected and these can be used for identification of terminal delta UA and its sulfate content. It was established with several disaccharides and a tetrasaccharide that glycosidic linkages and O- and N-sulfate groups are preserved in the remaining structures after removal of delta UA. These results indicate that the oxymercuration reaction will be applicable to generating series of GAG fragments containing unmodified sequences for biological activity studies. PMID- 7773986 TI - Characterisation by LSI-MS and 1H NMR spectroscopy of tetra-, hexa-, and octa saccharides of porcine intestinal heparin. AB - The characterisation of oligosaccharide fragments isolated from enzymatically depolymerised porcine intestinal heparin is required in order to probe structure/function relationships of heparin in anticoagulation, antiangiogenesis and antiviral activity. We have used both LSI-MS and 600-MHz 1H NMR with chemical shift assignment by comprehensive 1H-1H TOCSY experiments to fully characterise the major oligosaccharide components including 4 tetrasaccharides, 3 hexasaccharides, and 2 octasaccharides. One of the octasaccharides has not been identified previously and has the structure: delta UA(2S)-GlcNS(6S)-IdoA(2S) GlcNS(6S)-IdoA(2S)- GlcNS(6S)-GlcA-GlcNS(6S), where delta UA is 4,5-unsaturated uronic acid (4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid), GlcN is --> 4) alpha-D-glucosamine, IdoA is --> 4)-alpha-L-iduronic acid, GlcA is --> 4)-beta-D glucuronic acid, and 2-O-, 6-O-, and 2-N-sulfate are abbreviated to 2S, 6S, and NS, respectively. Nearly complete NMR proton chemical shifts are reported for this data set. In addition a novel approach involving oxymercuration-lipid conjugation was used to independently assign sulfate substitution on the delta UA residues. PMID- 7773987 TI - Full assignment of the NMR spectrum of the capsular polysaccharide from Streptococcus pneumoniae serotype 10A. PMID- 7773988 TI - A new synthesis of 6-O-acylsucroses and of mixed 6,6'-di-O-acylsucroses. AB - Various 6-O-acylsucroses were synthesized in good yields from unprotected sucrose in N,N-dimethylformamide and the appropriate 3-acylthiazolidine-2-thiones 6 or 3 acyl-5-methyl-1,3,4-thiadiazole-2(3H)-thiones 7. A selective ionization of the free sugar by sodium hydride or triethylamine, followed by acylation with 6, gave 2-O-acylsucroses which were subjected in situ to intramolecular isomerizations using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or an aqueous solution of triethylamine to yield 6-O-acylsucroses. The later were otherwise obtained directly when sucrose was acylated with 6 or 7 in the presence of DBU. Moreover, mixed 6,6'-di-O-acylsucroses were readily obtained from 6'-monoacylates by using a Mitsunobu reaction without involving the concomitant formation of the 3',4' epoxide. PMID- 7773989 TI - Transjugular intrahepatic portosystemic shunt in portal vein thrombosis: role of the right gastric vein with anomalous insertion. AB - Transjugular intrahepatic portosystemic shunt (TIPS) was performed in two patients with portal vein thrombosis. In both patients, hepatopetal flow had been maintained by an anomalous insertion of the right gastric vein (RGV) into the portal vein bifurcation and into the left portal branch respectively. In one patient, the main portal trunk could not be recanalized and the RGV was used as an accessory portal vein to place one stent for TIPS. In the other case, access through the partial portal-vein occlusion was gained and three stents were placed from the hepatic vein to the main portal vein distal to the thrombus. In portal vein thrombosis, the aberrant insertion of the RGV into the left or right portal branches may maintain patency of the intrahepatic portal system and, in case of unsuccessful recanalization of the porta, may represent the sole pathway for placing a TIPS. PMID- 7773990 TI - Palmaz stent dislodgement into the left pulmonary artery complicating TIPS: percutaneous retrieval and extraction after venotomy. AB - A Palmaz stent had dislodged into the left pulmonary artery after TIPS. After transfemoral catheterization of the left pulmonary artery, the stent was retrieved into the right femoral vein employing an angioplastic balloon catheter and finally extracted after surgical venotomy. PMID- 7773991 TI - Intentional occlusion of a transjugular intrahepatic portosystemic shunt. AB - The transjugular intrahepatic portosystemic shunt (TIPS) procedure is a well described means of treating portal hypertension and its complications. Occasionally, the consequences of this shunt prompt the desire for its subsequent obliteration. We report one unsuccessful and one successful method of TIPS occlusion. PMID- 7773992 TI - Dissecting pseudoaneurysm of the hepatic artery: a delayed complication of angioplasty in a liver transplant. AB - We report a 59-year-old female with a dissecting pseudoaneurysm of the allograft hepatic artery, as a delayed complication of percutaneous transluminal angioplasty (PTA). PTA of a severe anastomotic stenosis was successful, but complicated by a dissection involving the allograft hepatic artery. A large dissecting pseudoaneurysm developed and was incidentally detected during routine sonographic evaluation 14 months after PTA. Because of the extent of the pseudoaneurysm, percutaneous repair or surgical reconstruction was considered impossible. The patient underwent successful retransplantation 1 week after diagnosis. PMID- 7773993 TI - Double aortic arch in d-transposition of the great arteries complicated by tracheobronchomalacia. AB - Simultaneous occurrence of d-transposition of the great arteries and aortic arch malformations is very rare. A case of this malformation, the fourth case reported in the literature, is described. Despite successful surgery, tracheobronchomalacia was fatal at the age of 7 months. PMID- 7773994 TI - Anomalous origin of the right pulmonary artery from the ascending aorta: diagnosis by magnetic resonance imaging. AB - Anomalous origin of the right pulmonary artery from the ascending aorta is a rare congenital anomaly. Magnetic resonance imaging (MRI) was performed on three patients with anomalous origin of the right pulmonary artery from the ascending aorta. ECG-gated, T1-weighted, spin-echo MRIs and cine MRIs were obtained. In one patient, postoperative MRI was also obtained. Echocardiography and cardiac catheterization were performed in three patients and angiocardiography was performed in two. MRI clearly showed anomalous origin of the right pulmonary artery from the posterior aspect of the ascending aorta, as well as combined anomalies including patent ductus arteriosus, aortopulmonary window, and interruption of the aortic arch in all three patients. Echocardiography missed this anomaly in all three. We suggest that MRI is an accurate imaging modality in diagnosing anomalous origin of the right pulmonary artery from the ascending aorta, obviating the need to perform angiocardiography. PMID- 7773996 TI - Crossover approach with a J-shaped sheath for angioplasty of iliofemoral artery stenoses and occlusions. AB - Thirty patients with atherosclerotic stenoses or occlusions of iliofemoral arteries were treated from the contralateral approach using a newly designed J shaped sheath. Seven patients with stenoses and one with an occlusion were successfully dilated with balloon angioplasty. Twenty-two patients with occlusions were treated with urokinase infusion, 16 of whom received coaxial infusion with the J-shaped sheath and catheter. Complete thrombolysis was achieved in 18 patients. The treatment success rate was 100% in the stenotic group and 83% in the occlusion group. Initially, J-shaped sheaths were useful for treatment of iliofemoral artery lesions from the contralateral femoral artery. PMID- 7773997 TI - Re: Histological analysis of atherectomy specimens: an opportunity neglected to guide therapy preventing restenosis. PMID- 7773998 TI - An introduction to the Food and Drug Administration and how it evaluates new devices: establishing safety and efficacy. AB - Most physicians, and certainly the lay public, have only limited knowledge of the responsibilities and limits of the Food and Drug Administration (FDA) of the United States of America. Although laws as early as 1902 protected the public from unrestricted sale of unsafe drugs, it was not until 1976 that devices came under regulation. An obvious difference existed between regulatory control of drugs vs devices. The drug-based approach for evaluation was rejected in favor of a new system based on device class and its degrees of risk. The premarket notification process (510K), and the premarket approval application (PMAA) became the regulatory pathway for device approval. The investigational device exemption (IDE) became the mechanism for established safety and efficacy. Occasionally conflicts exist between industry and the FDA. Submission of poorly planned studies wastes FDA resources whereas prolonged approval times can be devastating to the small single product business that creates the majority of our new devices. A compromise is obviously necessary if we are to maintain our premier identity as a new device entrepreneurial center and avoid industry's migration to countries where the regulatory standards might be less rigid. PMID- 7773995 TI - Localization of small pulmonary nodules for thoracoscopic resection: use of a newly developed hookwire system. AB - We developed a stainless steel spring hookwire, 0.28 mm in diameter and 10 mm in length, with a 30-cm-long, 5-0 nylon monofilament suture firmly attached to its funnel-shaped end. A 21-gauge, 10-cm-long cannula was used as an introducer, and a 24-gauge, 10-cm-long blunt-pointed needle as a pusher. The hookwire was successfully placed into the target pulmonary parenchyma under computed tomography guidance in two patients with a small pulmonary nodule. The attached string served as a clear guide at thoracoscopy. Flexibility of the exposed suture through the skin eased wire management after placement. No wire dislodgement occurred. PMID- 7773999 TI - Treatment of postoperative residual hepatolithiasis after progressive stenting of associated bile duct strictures through the T-tube tract. AB - PURPOSE: The authors report their experience with the treatment of intrahepatic bile duct strictures associated with hepatolithiasis. METHODS: Eighty patients had multiple postoperative retained intrahepatic duct stones trapped behind intrahepatic biliary strictures. Before stone extraction, the strictures were opened gradually by semirigid dilators, followed by stent placement to create enough patency for stone removal. All procedures were carried out through the T tube tracts and were aided by cholangioscopy and electrohydraulic lithotripsy. RESULTS: Complete clearance of stones was achieved in 69 patients. Failure to dilate the strictures was due to acute and multiple ductal angulations. These included the right posterior inferior intrahepatic duct at its junction with the left intrahepatic ducts when it was more than 2 cm distal to the hepatic bifurcation, when the angle between the T-tube tract and the common bile duct was smaller than 90 degrees, and when stones were located in peripheral intrahepatic ducts with more than five angulations. CONCLUSION: This technique is considered safe and effective for complicated hepatolithiasis with intrahepatic biliary strictures. PMID- 7774001 TI - The role of magnetic resonance angiography in the diagnosis of subclavian steal. AB - PURPOSE: To compare magnetic resonance angiography (MRA) with digital angiography for diagnosis of subclavian steal syndrome. METHODS: A comparison study between MRA and digital contrast arteriography was carried out in 10 patients with suspected subclavian steal syndrome. Two of these patients were studied by MRA before and after percutaneous transluminal angioplasty (PTA). MRA was obtained on a 1.5 tesla superconductive magnet with linear head coil using a fast low angle shot (FLASH 2D) sequence in the axial plane as well as a fast imaging with steady state precession (FISP 3D) with velocity compensation gradient echo sequence in the coronal plane. The coronal images were used as source data for the construction of projection images with the use of a maximum-intensity pixel algorithm. The images were rotated from -45 degrees to 45 degrees in 15 degrees steps. RESULTS: All 10 patients had evidence of proximal subclavian artery obstruction and flow reversal in the ipsilateral vertebral artery. On MRA, consistent visualization of the affected vertebral artery in the FLASH 2D sequences and nonvisualization in the FISP 3D sequences was interpreted as an indirect sign of subclavian steal. The subclavian artery obstruction could not be assessed due to field size limits of MRA. CONCLUSION: MRA allows determination of flow reversal in the diagnosis of subclavian steal. PMID- 7774000 TI - Hepatocellular carcinoma: efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy. AB - PURPOSE: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatocellular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. METHODS: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. RESULTS: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%). CONCLUSION: TOCE appears to be most efficacious for HCC with the expanding growth pattern and HCC forming single nodules. Poor results are to be expected in HCC of replacing growth type and multinodular or massive growth types. PMID- 7774002 TI - Indirect portography enhanced by nicardipine versus prostaglandin E1. AB - PURPOSE: To compare nicardipine (NCR) and prostaglandin E1 (PGE1) for portal venous contrast enhancement on indirect portography in a retrospective study. METHODS: One milligram of NCR, a calcium antagonist, was injected into the superior mesenteric artery just prior to portography in 18 patients who had undergone otherwise identical portography using 20 micrograms PGE1 36-279 (mean 133) days before. All 18 patients had liver tumors and showed no changes in portal vein status in the interim. RESULTS: Using conventional film/screen angiography, NCR provided equally good portograms as PGE1 with respect to image density and image contrast. Systemic effects on blood pressure and heart rate were minimal and no other side effects were observed with NCR. CONCLUSION: NCR is an inexpensive drug and is expected to provide well-contrasted, indirect portograms on conventional film/screen angiography. PMID- 7774003 TI - The protective effect of portoarterial shunts after experimental hepatic artery embolization in rats with liver cirrhosis. AB - PURPOSE: The role of the portal system after hepatic artery embolization (HAE) was examined. METHODS: Using a Wistar strain rat model of liver cirrhosis, the route and occurrence of portoarterial (PA) shunts before and after HAE by scanning electron microscopic (SEM) and histologic methods were evaluated. HAE was performed with iodized oil and gelatin sponge particles. RESULTS: In the SEM study, PA shunts did not develop in normal rats regardless of whether they did (n = 10) or did not have HAE (n = 5). The cirrhotic rat model showed PA shunts in both HAE (n = 5) and non-HAE (n = 5) animals. PA shunts were established via the peribiliary plexus and direct arterioportal anastomosis. In the histologic study, the occurrence of PA shunts in liver cirrhosis was significantly increased by HAE (HAE = 6, non-HAE = 6, p < 0.01). CONCLUSION: The development of PA shunts, which help perfuse liver parenchyma, may explain why HAE can be safely performed in patients with liver cirrhosis. PMID- 7774004 TI - Alphavirus and flavivirus glycoproteins: structures and functions. PMID- 7774005 TI - The price of repression. PMID- 7774006 TI - Signal transduction and membrane traffic: the PITP/phosphoinositide connection. PMID- 7774007 TI - The Gordon Conferences--R.I.P.? PMID- 7774008 TI - ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. AB - The origin recognition complex (ORC) binds replicators in the yeast S. cerevisiae in a manner consistent with it being an initiator protein for DNA replication. Two-dimensional (2D) gel techniques were used to examine directly initiation of chromosomal DNA replication in temperature-sensitive orc mutants. Unlike in wild type cells, in orc2-1 and orc5-1 mutant cells, only a subset of replicators formed active origins of DNA replication at the permissive temperature. At the restrictive temperature, the number of active replicators was diminished further. Using a genetic screen, CDC6 was identified as a multicopy suppressor of orc5-1. 2D gel and biochemical analyses demonstrated that Cdc6p interacted functionally and physically with ORC. We suggest that ORC and Cdc6p form a prereplication complex at individual replicators and therefore cooperate to determine the frequency of initiation of DNA replication in the genome. PMID- 7774009 TI - Purification of Tetrahymena telomerase and cloning of genes encoding the two protein components of the enzyme. AB - Telomerase is a ribonucleoprotein DNA polymerase that catalyzes the de novo synthesis of telomeric simple sequence repeats. We describe the purification of telomerase and the cloning of cDNAs encoding two protein subunits from the ciliate Tetrahymena. Two proteins of 80 and 95 kDa copurified and coimmunoprecipitated with telomerase activity and the previously identified Tetrahymena telomerase RNA. The p95 subunit specifically cross-linked to a radiolabeled telomeric DNA primer, while the p80 subunit specifically bound to radiolabeled telomerase RNA. At the primary sequence level, the two telomerase proteins share only limited homologies with other polymerases and polymerase accessory factors. PMID- 7774010 TI - Identification of a nuclear receptor that is activated by farnesol metabolites. AB - Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that mediate the transcriptional activities of steroids, retinoids, and thyroid hormones. A growing number of related proteins have been identified that possess the structural features of hormone receptors, but that lack known ligands. Known as orphan receptors, these proteins represent targets for novel signaling molecules. We have isolated a mammalian orphan receptor that forms a heterodimeric complex with the retinoid X receptor. A screen of candidate ligands identified farnesol and related metabolites as effective activators of this complex. Farnesol metabolites are generated intracellularly and are required for the synthesis of cholesterol, bile acids, steroids, retinoids, and farnesylated proteins. Intermediary metabolites have been recognized as transcriptional regulators in bacteria and yeast. Our results now suggest that metabolite-controlled intracellular signaling systems are utilized by higher organisms. PMID- 7774011 TI - Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. AB - Despite the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2-/- mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation. Though platelets are absent, serum levels of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless, NF-E2-/- megakaryocytes proliferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-E2 must regulate critical target genes independent of the action of thrombopoietin. These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis. PMID- 7774012 TI - Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. AB - The solution structure of the specific complex between the high mobility group (HMG) domain of SRY (hSRY-HMG), the protein encoded by the human testis determining gene, and its DNA target site in the promoter of the mullerian inhibitory substance gene has been determined by multidimensional NMR spectroscopy. hSRY-HMG has a twisted L shape that presents a concave surface (made up of three helices and the N- and C-terminal strands) to the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site occurs exclusively in the minor groove and induces a large conformational change in the DNA. The DNA in the complex has an overall 70 degrees-80 degrees bend and is helically unwound relative to classical A- and B-DNA. The structure of the complex reveals the origin of sequence-specific binding within the HMG-1/HMG-2 family and provides a framework for understanding the effects of point mutations that cause 46X,Y sex reversal at the atomic level. PMID- 7774013 TI - Low pH induces swiveling of the glycoprotein heterodimers in the Semliki Forest virus spike complex. AB - Time-resolved cryoelectron microscopy reveals the first step in the conformational changes that enable membrane fusion in Semliki Forest virus. The neutral pH structure reveals a central cavity within the spike complex, plate like extensions forming a layer above the membrane, and the paths of the paired transmembrane domains connecting the trimeric spikes and pentamer-hexamer clustered capsid subunits. Low pH treatment results in centrifugal movement of E2, the receptor-binding subunit, centripetal movement of E1 to narrow the central cavity initiating the formation of an E1 trimer, and the extension of the E1 fusion sequence toward the target membrane. PMID- 7774014 TI - The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF activated phosphatidylinositol 3-kinase. AB - The serine/threonine protein kinase encoded by the Akt proto-oncogene is catalytically inactive in serum-starved primary and immortalized fibroblasts. Here we show that Akt and the Akt-related kinase AKT2 are activated by PDGF. The activation was rapid and specific, and it was abrogated by mutations in the Akt Pleckstrin homology (PH) domain. The Akt activation was also shown to depend on PDGFR beta tyrosines Y740 and Y751, which bind phosphatidylinositol 3-kinase (PI 3-kinase) upon phosphorylation. Moreover, Akt activation was blocked by the PI 3 kinase-specific inhibitor wortmannin and the dominant inhibitory N17Ras. Conversely, Akt activity was induced following the addition of phosphatidylinositol-3-phosphate to Akt immunoprecipitates from serum-starved cells in vitro. These results identify Akt as a novel target of PI 3-kinase and suggest that the Akt PH domain may be a mediator of PI 3-kinase signaling. PMID- 7774015 TI - Serpentine cAMP receptors may act through a G protein-independent pathway to induce postaggregative development in Dictyostelium. AB - The transcription factor G box-binding factor (GBF) is required for the developmental switch between aggregative and postaggregative gene expression, cell-type differentiation, and morphogenesis. We show that constitutive expression of GBF allows ectopic expression of postaggregative genes, but only in response to exogenous cAMP. GBF activation requires the serpentine cAMP receptors required for aggregation, but not the coupled G alpha 2 or the G beta subunit, suggesting a novel signaling pathway. In response to high cAMP, g alpha 2-null cells can bypass the aggregation stage, expressing cell type-specific genes and forming fruiting bodies. Our results demonstrate that the same receptors regulate aggregation and cell-type differentiation, but via distinct pathways depending upon whether the receptor perceives a pulsatile or sustained signal. PMID- 7774016 TI - Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. AB - The vertebrate hedgehog-related gene Sonic hedgehog (Shh) is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. We show here that SHH induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl 1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo. A single inducing molecule, SHH, therefore appears to mediate the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system. PMID- 7774017 TI - The Drosophila schnurri gene acts in the Dpp/TGF beta signaling pathway and encodes a transcription factor homologous to the human MBP family. AB - Decapentaplegic (dpp), a TGF beta-related ligand, plays a key role in Drosophila development. Although dpp receptors have been isolated, the downstream components of the signaling pathway remain to be identified. We have cloned the schnurri (shn) gene and show that it encodes a putative zinc finger transcription factor homologous to the human major histocompatibility complex-binding proteins 1 and 2. Mutations in shn affect multiple events that require dpp signaling as well as the transcription of dpp-responsive genes. Genetic interactions and the strikingly similar phenotypes of mutations in shn and the dpp receptors encoded by thick veins and punt suggest that shn plays a downstream role in dpp signaling. PMID- 7774018 TI - Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1. AB - Cytokines of the TGF beta superfamily regulate many aspects of cellular function by activating receptor complexes consisting of two distantly related serine/threonine kinases. Previous studies have indicated that Drosophila dpp uses similar signaling complexes and strictly requires the punt and thick veins receptors to transduce the signal across the membrane. Here, we show that the schnurri (shn) gene is required for many aspects of dpp signaling. Genetic epistasis experiments indicate that shn functions downstream of the dpp signal and its receptors. The shn gene encodes a large protein similar to a family of mammalian zinc finger transcription factors. The shn protein might therefore act as a nuclear target in the dpp signaling pathway directly regulating the expression of dpp-responsive genes. PMID- 7774020 TI - Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. AB - Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5 mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia. PMID- 7774019 TI - Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. AB - Although the mechanism of mammalian apoptosis has not been elucidated, a protease of the CED-3/ICE family is anticipated to be a component of the death machinery. Several lines of evidence predict that this protease cleaves the death substrate poly(ADP-ribose) polymerase (PARP) to a specific 85 kDa form observed during apoptosis, is inhibitable by the CrmA protein, and is distinct from ICE. We cloned a ced-3/ICE-related gene, designated Yama, that encodes a protein identical to CPP32 beta. Purified Yama was a zymogen that, when activated, cleaved PARP to generate the 85 kDa apoptotic fragment. Cleavage of PARP by Yama was inhibited by CrmA but not by an inactive point mutant of CrmA. Furthermore, CrmA blocked cleavage of PARP in cells undergoing apoptosis. We propose that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama. PMID- 7774021 TI - Micelle/water partition properties of phenols determined by liquid chromatographic method. Proposal for versatile measure of hydrophobicity. AB - Partition properties have been determined for 28 monosubstituted phenols in the sodium dodecylsulfate (SDS)/water system by micellar liquid chromatography (MLC), offering a useful and versatile method to estimate the hydrophobicity of compounds. The enthalpy and entropy terms of partition have also been determined from variable temperature experiments on MLC and are interpreted by such factors as molecular size and hydrogen-bond ability of the solute. The pi constants (pi, pi H and pi S) are determined from the experimental partition properties and applied to quantitative structure-activity relationships (QSAR) analysis, and their versatility supported. PMID- 7774022 TI - Duocarmycins, potent antitumor antibiotics produced by Streptomyces sp. structures and chemistry. AB - Seven novel potent antitumor antibiotics, duocarmycins A (1), C1 (2), C2 (3), D (4), B1 (5), B2 (6) and SA (7), were isolated from three independently collected Streptomyces sp. The complete structures, including absolute stereochemistry, were determined by spectral and chemical studies of those duocarmycins and several derivatives. Duocarmycins A (1) and SA (7) possess a 1,2,7,7a tetrahydrocycloprop[1,2-c]indol-4-one subunit, a common pharmacophore with that of CC-1065 (10) found from Streptomyces zelensis. PMID- 7774023 TI - Purines. LXX. An extension of the "phenacylamine route" to the syntheses of the 7 N-oxides of 6-mercaptopurine and 6-methylthiopurine, and antileukemic activity of some purine N-oxides. AB - A full account is given of the first syntheses of 6-mercaptopurine 7-N-oxide (4) and 6-methylthiopurine 7-N-oxide (5). The synthesis of 4 followed a "phenacylamine route", which started from condensation of 4,6-dichloro-5 nitropyrimidine (15) with N-(4-methoxybenzyl)phenacylamine to form the phenacylaminopyrimidine derivative (11) and proceeded through conversion into the mercapto derivative, intramolecular cyclization between the NO2 nitrogen atom and the phenacyl carbanion to give 6-mercapto-9-(4-methoxybenzyl)purine 7-N-oxide (12), and removal of the 4-methoxybenzyl group. S-Methylation of 12 and removal of the 4-methoxybenzyl group afforded 5. The location of the oxygen function in 4,5, and 12 was confirmed by X-ray crystallographic analysis of 5.H2O, which was shown to exist in the N(7)-OH form (19). A UV spectroscopic approach suggested that the neutral species of 4 exists in H2O as the N(7)-OH tautomer (21), whereas that of 5 exists as an equilibrated mixture of the N(7)-oxide (5) and the N(7)-OH (19) tautomers. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, the N-oxides 4 and 12 were found to be weakly cytotoxic. PMID- 7774024 TI - Disaccharides as endomannosidase inhibitors: syntheses of alpha homomannojirimycin and beta-homomannojirimycin linked to D-glucose and D-mannose. AB - 4-O-(alpha-D-Glucopyranosyl)-alphaHMJ (Glcalpha1,4HMJ), 4-O-(alpha mannopyranosyl)-alphaHMJ (Manalpha1,4alphaHMJ), 4-0-(alpha-glucopyranosyl) betaHMJ (Glcalpha1,4betaHMJ), and 4-0-(alpha-mannopyranosyl)-betaHMJ (Manalpha1, 4betaHMJ) were synthesized as endomannosidase inhibitors which are potentially useful both for probing the pathways of N-linked glycoprotein processing and for the chemotherapy of some viral diseases. PMID- 7774025 TI - Synthetic study of 2-[(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl) sulfinyl]-1H-benzimidazole analogs and their biological properties as novel proton pump inhibitors. AB - A series of 2-[(cycloalka[b]pyridinyl)sulfinyl]-1H-benzimidazoles (11) was synthesized and tested for antisecretory activity against pentagastrin-induced gastric acid secretion in rats. A novel benzimidazole derivative containing a cyclohepta[b]pyridine moiety was found to be the most potent among the congeners, which included five- to eight-membered cycloalka[b]pyridine ring systems. Some 2 [(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)sulfinyl]-1H- benzimidazole analogs (14) with various substituents on the aromatic rings showed superior properties to omeprazole (1) in biological examinations in vivo. A diastereoisomer, TY-11345 (28Ba), was selected as a promising agent for further evaluation. PMID- 7774026 TI - Optically active antifungal azoles. IV. Synthesis and antifungal activity of (2R,3R)-3-azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols. AB - (2R,3R)-3-Azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols (III) were prepared from (2R,3S)-3-methyl-2-(substituted phenyl)-2-(1H-1,2,4 triazol-1-yl)methyloxiranes (21a-f) by a ring-opening reaction with 1H-1,2,3 triazole and 1H-tetrazole and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The optically active oxiranes (21a--f) which serve as the key synthetic intermediates, were synthesized from 1-[(2R)-2-(3,4,5,6 tetrahydro-2H-pyran-2-yl)oxypropanoyl]morpholin e (24) and substituted phenylmagnesium bromide (23) via six steps in a stereocontrolled manner. The 3 (1H-1,2,3,-triazol-1-yl)-(IIIa) and 3-(2H-2-tetrazolyl)-2-butanol (IIId) derivatives showed strong protective effects against candidosis in mice. PMID- 7774028 TI - Synthesis and evaluation of novel nonpeptide angiotensin II receptor antagonists: imidazo[4,5-c]pyridine derivatives with an aromatic substituent. AB - Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4,5 c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4,5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4,5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats. PMID- 7774027 TI - Optically active antifungal azoles. V. Synthesis and antifungal activity of stereoisomers of 3-azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2- butanols. AB - The (2S,3S)-, (2R,3S)- and (2S,3R)-stereoisomers of (2R,3R)-3-azolyl-2 (substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols [(2R,3R)-1a--d] were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo to clarify the relationships between stereochemistry and biological activities. The results revealed that the in vitro antifungal activity in each set of the four stereoisomers [(2R,3R)-, (2S,3S)-, (2R,3S)- and (2S,3R)-1a--d] definitely paralleled the in vivo antifungal activity against candidosis in mice, and the order of potency was (2R,3R) >> (2R,3S) > or = (2S,3S) > or = (2S,3R). In addition, the four stereoisomers in each set were assessed for sterol biosynthesis-inhibitory activities in C. albicans and rat liver. The (2R,3R) isomer was found to exert a strong and selective inhibitory effect on the sterol synthesis in C. albicans as compared with that in rat liver. PMID- 7774029 TI - Chemical and chemotaxonomical studies of ferns. LXXXVII. Constituents of Trichomanes reniforme. AB - Five new glycosides, 3,4-dihydroxyphenethyl alcohol 4-O-caffeoyl-beta-D allopyranoside, (6S,13S)-13-beta-D-fucopyranosyloxy-6-(beta-D-fucopyranosyl -(1- >2)-[beta-D-fucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyloxy]) -cleroda-3,14 diene, (6S,13S)-13-beta-D-fucopyranosyloxy-6-(beta-D-quinovopyranosyl -(1-->2) [beta-D-fucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyloxy ])-cleroda-3,14-diene, (6S,13S)-13-alpha-L-arabinopyranosyloxy-6-(beta-D-fucopyranosyl-(1 -->2)-[beta-D fucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyloxy])- cleroda-3,14-diene and (6S,13S)-13-alpha-L-arabinopyranosyloxy-6-(beta-D-quinovopyrano syl-(1-->2) [beta-D-fucopyranosyl-(1-->4)-alpha-L-rhamnopy ranosyloxy])-cleroda-3,14-diene, were isolated, together with mangiferin and 6'-O-acetylmangiferin, from the fronds of a New Zealand fern, Trichomanes reniforme. PMID- 7774031 TI - Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative for oral administration at an exploratory stage of new drug development. AB - Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative were investigated. The hydrochloride form showed incompatibility with the excipients used for oral dosage forms. There were several crystal forms of the free base, namely, alpha-anhydrate, beta-anhydrate, monohydrate, and trihydrate. The trihydrate form was unstable. The degree of crystallinity of the beta-anhydrate form was difficult to control. The monohydrate form was difficult to manufacture with constant quality. The serum levels of the compounds in rats were almost related to the dissolution rates in the JP 1st disintegration medium from the discs. The serum level of alpha-anhydrate was the lowest. However, the dissolution rates from the formulations of alpha-anhydrate were improved. After oral administration of the improved formulation, the serum level of alpha anhydrate in beagle dogs was almost triple that after the oral administration of the capsule of the hydrochloride form. PMID- 7774030 TI - Six new presenegenin glycosides, reiniosides A--F, from Polygala reinii root. AB - Six new oleanane-type triterpene saponins, called reiniosides A-F, were isolated from the roots of Polygala reinii Fr. et Sav. and their structures were elucidated by spectroscopic and chemical means. PMID- 7774032 TI - Influence of formulation change on drug release kinetics from hydroxypropylmethylcellulose matrix tablets. AB - Examination was made of the release of indomethacin from hydroxypropylmethylcellulose (HPMC) matrices and the results were found to usually follow first order release kinetics. The release mechanism changed with formulation. HPMC content was the predominant controlling factor. As the HPMC content increased, drug release rate decreased, and the release mechanism gradually changed from Higuchi diffusion release to case II transport. Additives increased the release rate and enhanced Fickian diffusion. As drug content increased, release rate calculated from percent release data decreased while that calculated from mg release data increased. When indomethacin content was lower, drug release was diffusion controlled and when higher, non-Fickian transport or case II transport was apparent. Additive effects were also examined. Starch was found to most effectively maintain case II release. Complex additives containing starch were superior to any additive by itself. A multiple regression model was used to determine the relationship between response (release rate) and factors (content of HPMC and diluents), and on the basis of this model a formulation was established and found valid by agreement with data from the regression model. PMID- 7774033 TI - Heterocyclic betaines. XXII. Azinium(azolium) 4-nitrobenzimidazolate inner salts and their derivatives with several interannular spacers. Synthesis, characterization and antitrichomonal activity. AB - The synthesis of an ensemble of pyridinium(imidazolium) 4-nitrobenzimidazolate betaines and their derivatives with several interannular linkages has been explored. Their antiprotozoal activity has also been examined. PMID- 7774034 TI - Synthesis and antileukemic activity of chymotrypsin-activated derivatives of 3' amino-2',3'-dideoxycytidine. (Synthetic nucleosides and nucleotides. XXXIII. AB - 3'-Amino-2',3'-dideoxycytidine (8) was directly synthesized from 2' deoxycytidine. 2',3'-Dideoxy-3'-(N-acyl-L-phenylalanylamino)cytidines (acyl = butoxycarbonyl (9a), acetyl (9b), benzoyl (9c), and n-hexanoyl (9d)) were synthesized as chymotrypsin-activated prodrugs of 8. This N-protection was required for activation by chymotrypsin to 8. In vitro, compound 8 showed high cytotoxic activity against P388 cells, but the prodrugs 9a-d were ineffective. In vivo, however, these prodrugs showed much higher activity than 8 in mice bearing P388 cells. PMID- 7774035 TI - Controlled release by Ca(2+)-sensitive recombinant human tumor necrosis factor alpha liposomes. AB - Recombinant human tumor necrosis factor-alpha (rHuTNF) was entrapped in liposomes consisting of Egg phosphatidylcholine (EggPC) alone, EggPC-egg phosphatidic acid (EggPA) or EggPC-egg phosphatidylglycerol (EggPG). These liposomes, stored in vials, were stable for a month at 4 degrees C. The rHuTNF release from the liposomes were examined in rat plasma and phosphate buffered saline (PBS). rHuTNF was released from the liposomes containing EggPA in rat plasma. The release of rHuTNF was inhibited by EDTA and was induced in PBS containing CaCl2, indicating that this release is induced by Ca2+ ion in the plasma. The release of rHuTNF was promoted by an increase of the EggPA content. In conclusion, we could obtain stable liposomes in a vial and this liposome could immediately release rHuTNF in the rat plasma. Furthermore we were able to control the release rate of rHuTNF from these liposomes. PMID- 7774036 TI - Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes. AB - The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 63 male students. Four site polymorphisms (signal peptide insertion/deletion, XbaI, MspI and EcoRI) of the apo B gene, three RFLPs (AvaII, StuI, and HincII) of the LDL receptor gene, two SSCPs of the cholesterol 7 alpha hydroxylase gene and the common apo E genotypes were determined. The average reductions induced by diet in participants homozygous for the absence of the XbaI restriction site (X-X-) of the apo B gene compared to those harboring this site (X+) were: 14.5 mg/dl and 9.4 mg/dl for total cholesterol (TC) (p < 0.09) and 15.5 mg/dl and 7.9 mg/dl for LDL-C (p < 0.003), respectively. Differences in dietary responsiveness among the apo E, LDL receptor and the cholesterol 7 alpha hydroxylase genotypes were largely insignificant. Using the four apo B polymorphic sites, six unambiguous haplotypes were constructed and a model for their possible evolutionary relationship is presented. Genetic variation in the apo B gene region, as defined by haplotypes, accounted for 8.7% and 24.3% of the phenotypic variance in TC and LDL-C response to diet, respectively. Sequence analysis of a candidate locus, the putative LDL receptor binding region of apo B and its flanking sequences, was performed in two individuals, one homozygous for an apo B "hyper-responding" and another for the "lower-responding" haplotype, and no differences were found. In conclusion, haplotypes at the apo B gene locus are associated with dietary response of TC and LDL-C in young males. Yet, the sequence variation responsible for these differences is possibly located outside the putative LDL receptor binding domain. PMID- 7774037 TI - Risk estimates for developing motor neurone disease in first-degree relatives. AB - Patients with motor neurone disease resident in the three counties of South Glamorgan, Mid Glamorgan and Gwent (total population 1,394,400) from 1/11/91 to 31/12/92, were ascertained through general practitioners and neurology department records: 62 out of 71 (51 male, 20 female) index cases ascertained agreed to be visited. These individuals were clinically reviewed, had a detailed family history taken and, after discussion, had a blood sample taken for testing for the X-linked bulbospinal muscular atrophy mutation. The period prevalence of motor neurone disease was 5.02/100,000 with a mean age of onset of 59.4 (S.D. 12.9) years. One 66-year-old male was found to have the X-linked bulbospinal muscular atrophy mutation. A single, definite first-degree relative pair was identified, of whom only one was included in the data. The index cases had a total of 131 offspring and 173 siblings. The risk estimates, by current age, for these first degree relatives of patients with apparently sporadic motor neurone disease decreased from 1 in 85 at age 20 years to 1 in 1683 at age 80 years. These estimates require confirmation in an independent sample, as they are based on a single "event". PMID- 7774038 TI - Maternal 3;13 chromosome insertion, with severe pre-eclampsia. AB - A previously healthy young primigravida suffered very severe pre-eclampsia and was delivered at 32 weeks gestation. The baby was growth retarded with dysmorphic features, and died aged 4 days. Chromosome analysis of the baby revealed partial trisomy 13 resulting from recombination within a maternal insertion of part of 13q into 3p. To date, the maternal insertion has been identified in a further three members of the family and may have contributed to a number of spontaneous abortions, stillbirths and neonatal deaths in other family members. The various possibilities for recombination and malsegregation are discussed. An association between pre-eclampsia and trisomy 13 has been reported previously. To our knowledge this present paper constitutes the first report of partial trisomy for 13q occurring with pre-eclampsia. PMID- 7774039 TI - Increased frequency of the rare PstI allele (P2) in a population of CAD patients in northern Greece. AB - Restriction fragment length polymorphisms (RFLPs) at the apolipoprotein AI-CIII AIV gene cluster and their association with coronary artery disease (CAD) and lipid levels were studied in a Northern Greek population. Ninety-five patients with CAD and fifty-four normal controls, angiographically proven, were included in this study. Using genomic hybridization techniques, three polymorphic restriction sites were identified at this locus: the PstI at the 3' end of the apoAI gene, the SacI at the 3' non-coding region of the apoCIII gene and the PvuII at the intergenic region between the apoCIII-AIV genes. The rare allele (P2) arising from the absence of the PstI restriction site was observed with a significantly higher frequency (p < 0.01) in patients compared to normals (0.11 vs 0.02). In contrast, the rare allele for the SacI polymorphic site had a similar distribution among patients and controls (0.12 vs 0.16). The same was observed for the PvuII RFLP (0.04 vs 0.05). Correlation of lipid and apolipoprotein AI levels with the three RFLPs revealed no significant association, although apo AI and HDL were lower in patients with the P2 allele. Thus, in this Greek population, only the PstI polymorphism, among the polymorphic restriction sites examined, appears to be associated with CAD. PMID- 7774040 TI - Charcot-Marie-Tooth disease: molecular characterization of patients from central and southern Italy. AB - The syndrome of peroneal muscular atrophy, or Charcot-Marie-Tooth (CMT), disease represents the most common inherited peripheral neuropathy, with a prevalence of about 1 per 2500. The disease is usually transmitted in an autosomal dominant fashion, although it can display all the mendelian patterns of inheritance. The chromosome 17-linked form (CMT1a) appears to be the most common form of the disease in all the ethnic groups studied so far, Italians included, and is due to a tandem duplication in 17p11.2. In order to study the distribution of CMT types and to establish a genotype-phenotype correlation in patients from Central and Southern Italy, we collected 19 CMT pedigrees diagnosed in the years 1992-1993. Simple tandem repeats (STR) polymorphism analysis with the marker RM11-GT and Southern blotting with the probes pVAW409R3 and pVAW412 were performed, demonstrating a high prevalence (about 60%) of 17p duplication in the families studied. No clinical or electrophysiological differences were noted between CMT1 patients with or without 17p duplication, respectively. Two families affected by CMT2 showed no evidence of rearrangement at the D17S122 locus. These data are consistent with the hypothesis of a different molecular basis for CMT2. PMID- 7774041 TI - Familial microcephaly with severe neurological deficits: a description of five affected siblings. AB - Autosomal recessive microcephaly is usually characterized by normal developmental milestones and minor neurological deficits. In this report, we describe five siblings in one family with marked microcephaly, intractable seizures, quadriplegia and profound mental retardation. The recurrence risk of microcephaly when associated with devastating neurological deficits, as exemplified by this family, may be high and in such cases, the role of appropriate genetic counseling is of utmost importance. PMID- 7774042 TI - Dicentric chromosome Y associated with Leydig cell agenesis and sex reversal. AB - The nature of a non-mosaic marker Y chromosome observed in a pseudohermaphrodite patient with Leydig cell agenesis was investigated by high-resolution chromosome analysis and molecular probes from the Y chromosome. Cytogenetically, the marker chromosome appeared to be an isodicentric, with breakage in Yq11.21. Double copies of all Yp-specific loci tested, including SRY, were present. The most distal Yq portion detected in patient DNA was DXS278-C, which maps to interval D in the chromosome Yq deletion map. Fragment DXS278-B, which maps to deletion interval E, was absent. The possible relationship between this cytogenetic abnormality and Leydig cell agenesis, a finding never reported in association with Y chromosome rearrangements, is discussed. PMID- 7774043 TI - Sperm chromosome complements in a man heterozygous for a reciprocal translocation 46,XY,t(9;13)(q21.1;q21.2) and a review of the literature. AB - Sperm chromosome complements were studied in a man heterozygous for a reciprocal translocation t(9;13)(q21.1;q21.2). A total of 89 spermatozoa were karyotyped after in vitro penetration of hamster eggs. The frequencies of alternate, adjacent 1 and adjacent 2 segregations were 46.9%, 35.8% and 17.3% respectively. For alternate segregation, the number of normal spermatozoa (21) was not significantly different from the number of spermatozoa carrying a balanced form of the translocation (17), as theoretically expected. The proportion of spermatozoa with an unbalanced form of the translocation was 53.1%. There was no evidence for an interchromosomal effect since the frequency of numerical abnormalities (unrelated to the translocation) was within the normal range of control donors. Data from a total of 31 reciprocal translocations studied by sperm chromosomal analysis were reviewed. PMID- 7774044 TI - Factors influencing whether or not couples seek genetic counselling: an explorative study in a paediatric surgical unit. AB - To investigate the factors influencing whether or not couples seek genetic counselling, the parents of 37 children with a major congenital anomaly were interviewed at home. All the children had been admitted to the Intensive Care Unit (ICU) of the Department of Paediatric Surgery. After physical examination of the child, the consultant clinical geneticist stated that genetic counselling was indicated for the parents. Whether they sought genetic counselling was left to the parents to decide. Eighteen of the 37 parents had sought genetic counselling. Assessment of the joint influence of a number of factors revealed that two factors were separately paramount in distinguishing between couples who did seek genetic counselling and those who did not: whether parents considered genetic counselling useful in their case shortly after the birth of their affected child, and whether the couple was clearly and correctly informed about the indication for genetic counselling. The intention to have a subsequent pregnancy was not associated with whether or not couples sought genetic counselling. Loss of information was observed: 1/3 of the referrals for genetic counselling mentioned on the written consultation forms were not stated in the discharge letters. This loss of information could have been reduced by a) routinely including the indication for genetic counselling in the discharge letter and b) appointing a coordinating physician to ensure that the parents were informed clearly about the availability of genetic counselling. Resistance to genetic counselling needs to be respected by the physician. Exploring its background might help to reduce this resistance. PMID- 7774045 TI - Antley-Bixler syndrome and esophageal atresia in a patient with trisomy 21. AB - The Antley-Bixler syndrome (ABS) is characterized by craniofacial, skeletal and urogenital anomalies. While most patients with ABS die of severe respiratory complications in their first months, long-term survivors have been reported. We report an infant girl, born to a consanguineous couple, with craniofacial and skeletal anomalies, consistent with ABS, in addition to atresia of the esophagus and trisomy 21. PMID- 7774047 TI - Occurrence of disseminated intravascular coagulation (DIC) in active systemic anaphylaxis: role of platelet-activating factor. AB - The possible occurrence of DIC in active systemic anaphylaxis was investigated in mice. Induction of active systemic anaphylaxis resulted in the development of DIC symptoms such as thrombocytopenia, prolongation of prothrombin time, hypofibrinogaemia, and elevated level of fibrinogen/fibrin degradation products. In addition, in histological examinations, massive congestion and cellular infiltration in pulmonary interstitia, and considerable haemorrhage in renal medullae were observed. All these changes were nearly completely prevented by pretreatment with platelet-activating factor (PAF) antagonist (BN 50739). Moreover, the same haematological and morphological changes were produced by a bolus injection of PAF. These data strongly suggest that DIC occurs in active systemic anaphylaxis and PAF plays a pivotal role in the development of DIC in anaphylaxis. PMID- 7774048 TI - Immune responsiveness to inhaled antigens: local antibody production in the respiratory tract in health and lung diseases. AB - The pulmonary defence mechanism in summer type hypersensitivity pneumonitis induced by Trichosporon cutaneum was investigated. We have studied the antibody response to fungal antigens in sera and bronchoalveolar lavage (BAL) fluids from patients with summer type hypersensitivity pneumonitis, bird fancier's lung, interstitial pneumonia associated with collagen vascular disease (INT-PNE), and from normal volunteers. Antigens extracted from fungi frequently isolated from home environments were used in ELISA to detect IgG and IgA antibodies in sera and BAL fluids. The results of the present study show that antibody titre in the respiratory tract to a variety of fungi from home environments is modulated by ongoing pulmonary inflammation, and that antibody production against inhaled antigens is altered by pulmonary inflammation resulting from diverse pathogenesis. This study concludes that the preexisting pulmonary inflammatory disease alters antibody production in the respiratory tract in response to inhaled fungi, and that the type of alteration depends in part on the etiology of the preexisting disease. PMID- 7774046 TI - Inhibition of gene expression by anti-sense oligodeoxynucleotides. PMID- 7774049 TI - Presence of mRNA for interferon-gamma (IFN-gamma) in blood mononuclear cells is associated with an active stage I sarcoidosis. AB - Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells obtained from sarcoidosis patients were investigated for the presence of mRNA for IFN-gamma. RNA was extracted from freshly obtained cells. In 12 cases PBMC were studied and in seven cases BAL cells were also available for concomitant investigation. In eight patients mRNA for IFN-gamma was present in blood and was significantly associated with stage I disease (P = 0.030). By comparison, BAL cells were less frequently positive for IFN-gamma transcripts (P = 0.039). Only one patient had simultaneous expression of IFN-gamma gene in blood and BAL cells. All other patients including four positive in blood were negative in BAL. The presence of IFN-gamma transcripts in PBMC was significantly associated with the capacity of these cells to generate IFN-gamma in unstimulated cultures. PBMC from patients showing IFN-gamma mRNA in blood were frequently high IFN-gamma producers in anti-CD3 MoAb-stimulated cultures. PMID- 7774050 TI - Two novel cationic staphylococcal proteins induce IL-2 secretion, proliferation and immunoglobulin synthesis in peripheral blood mononuclear cells (PBMC) of both healthy controls and patients with common variable immunodeficiency (CVID). AB - Two cationic proteins, a neutral phosphatase (NP-tase) and a 70-kD protein (p70) were isolated from Staphylococcus aureus by ion exchange chromatography. We compared their properties to those of the well established B cell mitogen of whole, fixed Staph. aureus strain Cowan I cells (SAC). Both purified proteins were able to induce immunoglobulin synthesis in PBMC cultures of healthy donors. NP-tase and p70 also induced immunoglobulin synthesis of PBMC from those patients with CVID who were also responsive to SAC plus IL-2 stimulation. Immunoglobulin synthesis in response to NP-tase and to p70 was time- and dose-dependent and could be inhibited by addition of specific antibodies against the proteins. In contrast to SAC, no addition of exogenous IL-2 was necessary to obtain maximal immunoglobulin synthesis induced by NP-tase or p70. However, neither protein was able to induce immunoglobulin synthesis in B cell-enriched cultures. High amounts of IL-2 were found in supernatants of PBMC from healthy donors following stimulation with low concentrations of NP-tase or p70, and this was associated with vigorous lymphocyte proliferation. Both proteins behave like typical antigens, and not like lectins or superantigens, since an NP-tase-stimulated T cell line showed an antigen-specific, MHC-restricted secondary response. In addition, no preferential T cell receptor V beta chain usage was found with eight V beta-specific MoAb. It is likely that the two proteins induce antigen-specific T cell activation, which is then followed by polyclonal activation of B cells via CD40 receptors and cytokine release. PMID- 7774051 TI - HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals. AB - In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens. PMID- 7774052 TI - The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants. AB - The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell ELISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-gamma) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function. PMID- 7774053 TI - Response of scid mice to establishment of Leishmania major infection. AB - The initiation of Leishmania major infection in susceptible BALB/c mice is regulated by interferon-gamma (IFN-gamma). To examine further the mechanisms of IFN-gamma-dependent regulation of the establishment of L. major, we studied the characteristics of the infection in severe combined immunodeficient (scid) mice. In the first 2 weeks of infection, we observed a delay in the development of the lesions in the footpads and lower numbers of parasites in scid compared with BALB/c mice. By week 5 after infection, the size of the leishmanial lesion was similar in both strains of mice, but the number of parasites in scid mice was 100 fold higher than in BALB/c. Treatment with anti-IFN-gamma during the establishment of L. major did not alter the course of infection in scid mice, while it exacerbated lesion development in BALB/c mice. Macrophages from scid mice were unable to kill L. major when stimulated with IFN-gamma in vitro, and produced lower levels of nitric oxide compared with macrophages from susceptible BALB/c or the resistant C57Bl/6 mice. We examined whether delayed lesion development in scid mice was due to their inability to mount appropriate inflammatory responses. While significantly fewer nucleated cells were present in the footpads of scid mice compared with BALB/c, 2 and 3 weeks after infection, no difference in inflammatory response between scid and BALB/c mice was observed in response to L. major antigen in the footpads. In contrast, there was a dramatic increase in the number of cells in the popliteal lymph nodes of BALB/c mice. Decreased inflammatory responses of scid mice in the footpad (at the site of infection) may contribute to slower development of leishmanial lesions during the first 2 weeks of infection. PMID- 7774054 TI - The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B. AB - To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis. PMID- 7774055 TI - Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD). AB - IBD is characterized by increased serum concentrations of different cytokines. IL 10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL 10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD. PMID- 7774056 TI - Expression of a unique protein on colon cancer cells that reacts with a novel monoclonal antibody and ulcerative colitis serum. AB - We earlier developed a MoAb, 7E12H12 (IgM isotype), against a protein present in normal colonic epithelial cells. To examine if 7E12H12-reactive protein is expressed in colon cancer cells and is recognized by ulcerative colitis (UC) associated autoantibody, we investigated several colon cancer cell lines. 7E12H12 reactivity against the cells was examined by indirect immunofluorescence assay and whole cell ELISA against six colon cancer cell lines HT-29, LoVo, COLO 205, DLD-1, LS 180 and SW 1116. A competitive ELISA was developed using 7E12H12 MoAb and patients' serum to examine the cross-reactive antibodies in the serum. Among the six colon cancer cell lines only LS 180, DLD-1 and SW 1116 reacted with 7E12H12 MoAb, while others did not. The mean (+/- s.e.m.) inhibition of the binding of 7E12H12 MoAb to LS 180 cells by UC serum (n = 51) was 42 +/- 2.1%, whereas in normal subjects (n = 17) it was 14 +/- 2.6%, in Crohn's disease (n = 19) it was 15.3 +/- 2.5%, in infectious diarrhoea (n = 10) it was 11% +/- 3%, and in systemic lupus erythematosus (n = 10) it was 2% +/- 0.6%. The inhibition by the UC group was significantly (P < 0.001 - < 0.0001) higher than any of the non UC groups, and this inhibition was mainly by IgG1 antibody. The protein in the specific colon cancer cells recognized by the 7E12H12 MoAb cross-reacts with UC IgG1 antibody and may provide an in vitro system to examine the autoimmune mechanisms in UC. PMID- 7774057 TI - Molecular heterogeneity of antigen- or idiotype-induced anti-thyroglobulin monoclonal autoantibodies. AB - To define the molecular basis of the cognitive interaction in experimental autoimmune thyroiditis (EAT), we sequenced the variable regions of monoclonal autoantibodies to thyroglobulin (Tg), specific or not for the F40D peptide, a Tg peptide capable of inducing EAT in CBA/J mice. Three MoAbs were obtained by immunization with syngeneic Tg of CBA/J (3B8G9, 2F6F2) or C57Bl/6 (4D11F4) mice. 3B8G9 was specific for F40D peptide, whereas 2F6F2 and 4D11F4 were not. Two others were raised in CBA/J mice by manipulation of idiotypic pathways: B12 resulted from the immunization with one Ab2 beta, bearing the internal image of one F40D epitope, and TA2 from the immunization with F40D-specific cytotoxic HTC2 T cells. B12 and TA2 were both specific for F40D. All hybridomas expressed different members of the J558 VH family, except 3B8G9 which expressed a Q52 VH gene segment. These data led us to hypothesize that regulatory anti-id autoantibodies used members of one VH family located in the 5'-end of the VH locus, whereas EAT-associated autoantibodies used a member of one of the most D proximal VH family. As expected, no homologies were found when anti-F40D monoclonal autoantibodies were compared with two other monoclonal autoantibodies displaying a different epitopic specificity. Among the anti-F40D monoclonal autoantibodies, one histidine residue located in position 35 of the CDR1 region was constantly found. Moreover, TA2 and B12 exhibited two common amino acids in their CDR3 regions, one glycine and one tyrosine, in positions 98 and 99, respectively. Striking homologies were found between TA2 and one anti-polyGAT MoAb, and between 3B8G9 and some anti-phenyloxazolone (phOx) monoclonal autoantibodies. Lastly, the VK sequence from 4D11F4 was identical at the amino acid level to the VK sequence from another monoclonal autoantibody, 81B1, which was previously raised towards syngeneic Tg in CBA/J mice. Our data imply that anti-idiotypic regulatory circuits in EAT might be generated by a heterogeneous population of B cells rather than obtained by a single dominant B cell population. PMID- 7774058 TI - Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. AB - The mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown. Mesangial IgA is of the IgA1 subclass, and since no consistent antigenic target for the IgA1 has been described, we have investigated the glycosylation of the molecule, as a potential non-immunological abnormality which may contribute to its deposition. IgA1 is rich in carbohydrate, carrying N-linked moieties in common with IgG, but also O-linked sugars, which are rare in serum proteins, and not expressed by IgG or IgA2. Lectin binding assays were designed to examine the expression of terminal galactose on the N-linked carbohydrate chains of purified serum IgG and IgA1, and the O-linked sugars of IgA1 and C1 inhibitor (one of the very few other serum proteins with O-linked glycosylation). No evidence was found for abnormalities of N-linked glycosylation of either isotype in IgA nephropathy compared with matched controls. However, in IgA nephropathy, reduced terminal galactosylation of the hinge region O-linked moieties was demonstrated; this was not seen in C1 inhibitor, which showed normal or increased galactosylation of the O-linked sugars. This abnormality of IgA1 has considerable implications for the pathogenesis of IgA nephropathy, since the O-linked sugars lie in an important functional location within the IgA1 molecule, close to the ligand of Fc receptors. Changes in the carbohydrates in this site may therefore affect interactions with receptors and extracellular proteins, leading to anomalous handling of the IgA1 protein in this condition, including failure of normal clearance mechanisms, and mesangial deposition. PMID- 7774059 TI - Increased IL-2, IL-4 and interferon-gamma (IFN-gamma) in steroid-sensitive nephrotic syndrome. AB - We investigated the production of cytokines by peripheral blood mononuclear cells (PBMC) and serum cytokine concentrations in children with steroid-sensitive idiopathic nephrotic syndrome (SSNS). PBMC from patients off treatment were collected during remission and relapse and cultured in medium alone or stimulated with calcium ionophore plus phorbol myristate acetate. Control PBMC were taken from healthy age-matched children. IL-2 was measured by bioassay, IL-4 by immunoradiometric assay, and IL-8 and IFN-gamma by ELISA. After 24 h culture without stimulation, IL-2, IL-4 and IFN-gamma were not detectable in the supernatant in any of the children. After stimulation, the supernatant concentrations of IL-2 (median 172 U/ml at 24 h) and IL-4 (160 pg/ml at 24 h; 210 pg/ml at 72 h) were significantly increased in relapse compared with remission (IL-2 37 U/ml; IL-4 65 pg/ml and 60 pg/ml) and controls (IL-2 69 U/ml; IL-4 40 pg/ml and 40 pg/ml) (P < 0.05). The concentration of IFN-gamma was not significantly increased in relapse compared with remission and controls (600, 325, and 145 U/ml, respectively, at 72 h). IL-8 concentrations were similar in relapse, remission and controls with stimulation (median 32, 40 and 40 ng/ml, respectively) and without (30, 17 and 10 ng/ml). IL-2 was not detectable in serum, but IL-4, IL-8 and IFN-gamma were measurable in about half the patients, both in relapse and remission, though were virtually undetectable in controls. We conclude that relapse of SSNS in children is associated with T lymphocyte activation with release of IL-2, IL-4 and IFN-gamma. PMID- 7774060 TI - Antibodies to small ribonucleoprotein and to 73-kD heat shock protein: two distinct markers of mixed connective tissue disease. AB - We set out to discover whether antibodies to small ribonucleoprotein antigens (RNP) and to 73-kD heat shock protein (hsp 73) which have been proposed as markers of mixed connective tissue disease (MCTD) recognize different epitopes. MCTD serum was immunoadsorbed on hsp 73-coupled Sepharose and the affinity retained, and non-retained fractions were checked by immunoblotting for recognition of either purified bovine hsp 73 or calf thymus extract RNPs. The hsp 73 affinity-bound serum fraction recognized hsp 73 but not RNP antigens, the reverse being true for the non-retained fraction. We conclude that anti-hsp 73 and anti-RNPs are distinct markers of MCTD. PMID- 7774062 TI - Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus. AB - This study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery of a child with NLE (21 with congenital heart disease block (CHB) and 20 with dermatologic NLE) and 19 sera from anti-Ro and/or anti-La antibody-positive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La and anti-r Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-r-La antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (0.67 +/- 0.43 versus 0.14 +/- 0.30; P < 0.0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0.51 +/- 0.45 versus 0.83 +/- 0.37 respectively; P = 0.0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0.77 +/- 0.35) compared with non-NLE mothers (0.29 +/- 0.39; P < 0.0001). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0.82 +/- 0.37 versus 0.71 +/- 0.74; P = 0.32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (5.1 +/- 0.54 versus 2.3 +/- 0.54 respectively; P < 0.001). More importantly, when we examined the individual polypeptides, we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30% versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference in the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774061 TI - Purification of antigenically intact Ro ribonucleoproteins; biochemical and immunological evidence that the 52-kD protein is not a Ro protein. AB - Anti-Ro sera immunoprecipitate Ro ribonucleoproteins (RNPs) from human cell extracts. Ro RNPs are biochemically heterogeneous particles whose functions are unknown and whose exact composition remains controversial. In addition to 60-kD Ro and to La proteins, a 52-kD polypeptide (p52) has been proposed to be a stable component of the Ro RNPs. To confirm the immunological studies supporting this hypothesis, we have biochemically purified Ro RNPs from HeLa cells using non denaturing conditions. Ro RNPs segregated into three distinct populations, one of which only contained hY5 RNA (RohY5 RNPs). No p52 co-purified with Ro RNPs. Despite the absence of p52, purified Ro RNPs had biochemical and immunological properties identical to those of unfractionated Ro RNPs. Many anti-Ro sera only recognize p52 in immunoblots, and are said to be monospecific anti-p52. Preincubation with purified RohY5 RNPs (free of p52) of all human anti-Ro (including so-called monospecific anti-p52) sera abolished their capacity to immunoprecipitate Ro RNPs from unfractionated HeLa cell extracts. Conversely, preincubation of anti-Ro sera with purified p52 protein specifically inhibited recognition of p52 in immunoblots, but did not interfere with immunoprecipitation of Ro RNPs. Our data demonstrate that anti-p52 antibodies do not target intact Ro RNPs, nor do they target the native 60-kD Ro protein. Contrary to previous reports, p52 protein is not a stable component of antigenically intact Ro RNPs. PMID- 7774064 TI - Composition and biological behaviour of immune complexes isolated from synovial fluid of patients with juvenile rheumatoid arthritis (JRA). AB - Data published from in vitro studies have shown that IgM-rheumatoid factor (RF) bearing immune complexes possess several biological features that may contribute to their pathogenicity. However, no studies have demonstrated that such complexes exist at sites of inflammation in children with rheumatoid disease. We used two methods of sequential column chromatography to purify immune complexes from synovial fluids of children with JRA. We demonstrate that high molecular weight complexes contain IgM-RF, have not bound C4 in vivo, but activate the classical pathway in vitro. In contrast, complexes which have bound C3 in vivo do not contain IgM-RF and are weak complement activators in vitro. PMID- 7774063 TI - Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial functional alterations. AB - Polyclonal anti-dsDNA and anti-ssDNA antibodies (PoAb) that showed significant binding to human umbilical vein endothelial cells (HUVEC) were isolated from eight patients with systemic lupus erythematosus (SLE). Anti-dsDNA PoAbs from five patients and anti-ssDNA PoAbs from seven patients demonstrated enhanced binding to HUVEC during active disease, compared with PoAbs obtained from corresponding patients during remission. Reduction of the DNA content in the PoAb preparations by DNase treatment was associated with enhanced binding to HUVEC in 20 of 32 PoAbs tested, which included 75% 'active disease' PoAbs, and with reduced binding to HUVEC in three of 32 PoAbs tested, all obtained during remission. Such altered endothelial cell binding was reversed with DNA reconstitution. Binding of the remaining nine PoAbs to HUVEC was not altered by variations in their DNA content. Induced plasma membrane expression of E selectin, but reduced expression of vascular cell adhesion molecule-1 (VCAM-1) by HUVEC, was observed following incubation of HUVEC with 'active disease' PoAbs from three and two of the eight patients, respectively. PoAbs and serum samples from two of the eight patients during active disease induced von Willebrand factor release from HUVEC, which was not observed during remission. We conclude that anti-DNA antibodies from selected patients with SLE can bind to endothelial cells. Correlation between cellular binding and disease activity suggests that such binding of anti-DNA antibodies to endothelial cells could be of pathogenic significance. Preliminary data also suggest that the expression of adhesion molecules and haemostatic factor(s) by endothelial cells may be modified following their binding by anti-DNA antibodies. PMID- 7774066 TI - Flow cytometric analysis of peripheral blood lymphocyte subset light scatter characteristics as a means of monitoring the development of rat small bowel allograft rejection. AB - This investigation used flow cytometry to monitor peripheral blood lymphocyte morphology after rat small bowel transplantation. Preliminary studies demonstrated that in vitro activated peripheral blood lymphocytes exhibited increased cell size and granularity as measured by flow cytometric analysis of forward (FSc) and side (SSc) light scatter characteristics. The formation of distinct 'activated' light scatter regions by such lymphoblastoid transformation occurred concomitantly with up-regulated p55IL-2R expression. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats without immunosuppression. Animals receiving isografts served as controls. Peripheral blood lymphocyte subsets were identified using appropriate MoAbs, and the light scatter characteristics of each cell subset were determined by backgating strategies. Increased proportions of activated alpha/beta T cell receptor (TCR)-positive cells could be detected in allografted animals as early as day 2 post-transplantation. B cells showed peak activation by day 4, at which time the proportion of activated cells was over two-fold greater than that seen in untransplanted animals--few activated B cells were detected in isografted animals. Resting natural killer (NK) cell light scatter regions only partially overlap with those of resting T and B lymphocytes, but in allografted animals almost the entire NK population fell outside the resting lymphocyte gate by day 2 post-transplantation, an activation state which was maintained until day 4. These findings associate peripheral blood cell subset lymphoblastoid transformation with developing small bowel allograft rejection. Importantly, changes were detected early and prior to the onset of overt rejection. These data suggest that analysis of peripheral blood lymphocyte light scatter properties may provide an insight into in vivo immune status after small bowel transplantation. PMID- 7774067 TI - Age-related changes in surface antigens on peripheral lymphocytes of healthy children. AB - The age-related changes in proportion of various subsets within lymphocytes were investigated in cord blood and peripheral blood from healthy children and adults. The percentages of T and B cells did not show age-related changes, whereas natural killer (NK) cells increased significantly with age. Within lymphocytes or the CD3+ T cell population the proportion of CD45RAbright+ lymphocytes decreased and that of CD45RO+ cells increased, while that of CD45RAdim+ cells showed no age related change. Within lymphocytes, the percentage of CD45RAbright+ CD4+ cells decreased, together with a decline of that of CD4+ cells. The proportions of CD45RAbright+ CD8+ cells and S6F1bright+ CD8+ cells increased with age, and the age-dependent increase of the proportion of CD8+ cells seems to be mainly attributable to the increases in these subsets. The CD45RAdim+ CD4+ and CD45RAdim+ CD8+ cells co-expressing CD45RO at a low level nevertheless showed no age-related changes. In gamma delta T cells, both delta TCS1+ and delta TCS1- T cells increased with age, but the delta TCS1- gamma delta T cells increased more than the delta TCS1+ subset. Among lymphocytes, the percentages of CD20+, CD21+ and CD22+ cells remained similar, with no age-related changes, but the proportion of CD5+ cells within lymphocytes or B cells decreased. The proportions of CD16+ NK cells among lymphocytes increased with age, and this change was attributable to the increase of CD56+ cells. PMID- 7774065 TI - Gamma delta T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. AB - Autoreactive alpha beta T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). gamma delta T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of gamma delta T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate gamma delta T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). gamma delta TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. gamma delta TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the V gamma 3 and V delta 1 transcripts, whose expression was prominent among gamma delta positive patients. DNA sequence analysis of V gamma 3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the V gamma 3-N-J gamma junctional domain. No amino acid sequence similarities were evident within the V delta-N-D delta-N-J delta region of V delta 1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike alpha beta T cells, gamma delta T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of gamma delta TCR gene expression detected among these patients implies that gamma delta T cell infiltration, when it occurs, is a secondary event perhaps resulting from non specific inflammatory processes. PMID- 7774068 TI - Incidence and outcome of pauci-immune necrotizing and crescentic glomerulonephritis in adults. AB - During a seven-year period (1986-1992) 719 adults (age > 16 years) underwent diagnostic renal biopsy in Stockholm (adult population 1.2 million). Seventy-one (10%) new cases of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) with or without systemic vasculitis were found: 39 females and 32 males (median age 67, range 20-84 years). The mean yearly incidence for the whole period was 0.8/100,000 population. The yearly incidence doubled from 0.6 before to 1.2/100,000 population after 1990. The incidence was highest among those > 65 years of age. Age-corrected incidences for this age group increased from 1.4 before to 3.9/100,000 after 1990. Anti-neutrophil cytoplasmic antibodies (ANCAs) tested in 60, showed antibodies against proteinase 3 (PR3) in 29 patients, against myeloperoxidase (MPO) in 26 and none in five patients. Mortality was highest in the early stages of the disease. From a total of 11 patients, 7 (15%) died within 2.5 months of diagnosis. Forty-six out of all 71 patients with NCGN belonged to the catchment area of our clinic and were studied in more detail. Twenty-six had microscopic polyangiitis (ANCAs were analyzed in 24, of these 16 had anti-MPO, 6 anti-PR3, 2 had none), 13 had Wegener's granulomatosis (ANCAs were analyzed in all, of these 12 had anti-PR3, 1 anti-MPO) and seven had disease limited to the kidneys (ANCAs were analyzed in 6, 5 had anti-MPO, one was negative). At the time of diagnosis, 16 patients had s-creatinine < 300 mumol/l while 14 patients were dialysis-dependent (seven only temporarily). All patients received immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774069 TI - Renal structure and function effects after low dose cyclosporine in psoriasis patients: a preliminary report. AB - Our studies on the treatment of psoriasis with cyclosporine A (CSA) have demonstrated efficacy at doses < 5 mg/kg/day. However, the nephrotoxicity of CSA at these low doses is not known and is the focus of this current study. Twenty nine patients prospectively had pretherapy assessment of renal function including serum creatinine and glomerular filtration rate (GFR). GFR was also measured while receiving CSA as well as posttherapy. These functional studies were compared with renal biopsies taken one month after discontinuing the drug. Pretherapy GFR values were normal in all of our subjects. However, by midstudy GFR values had dropped significantly in many patients. This trend continued so that at the end of the study mean GFR values had decreased by 12% with slightly over one quarter of the patients having reductions in GFR of at least 25%. Renal biopsy findings correlated well with the functional studies in particular the GFR, with those patients having the greatest reduction in GFR showing the most renal scarring. Thus, CSA at doses < 5 mg/kg/day induces variable chronic renal injury which correlates most closely with changes in the GFR. PMID- 7774070 TI - Efficacy of cyclosporin A (CyA) in psoriasis: an overview of dose/response, indications, contraindications and side-effects. AB - Since 1985, the efficacy of cyclosporin A (CyA) in severe psoriasis has been evaluated in a number of open and controlled studies, all of which have clearly established CyA as an effective antipsoriatic agent. The efficacy of CyA has also provided new insights into the pathophysiology of psoriasis. The effects of CyA treatment can be seen within weeks; they are dose-dependent and quickly reversible on stopping treatment. Hypertension and nephrotoxicity remain the greatest concerns associated with long-term use. In general, the incidence of hypertension is approximately 10%. A dosage of approximately 2.5-5 mg/kg/day of CyA induces a slight, but significant, dose-dependent increase in serum creatinine. Studies of pre- and post-treatment renal biopsies have also disclosed slight, but significant, increases in interstitial fibrous tissue which are negatively correlated to creatinine clearance. This review assesses the current knowledge of the prospects of CyA in the treatment of psoriasis with respect to dose/response, indications, contraindications and side-effects. PMID- 7774071 TI - A prospective study of cortical scarring in acute febrile pyelonephritis in adults: clinical and bacteriological characteristics. AB - Previous reports have demonstrated lesions on computerized axial tomography (CT), and nuclear scintigraphy (DMSA) in acute pyelonephritis (PN). We undertook a prospective study of all patients presenting to our hospital with PN over 40 months. Patients who fulfilled diagnostic criteria, were treated with intravenous antibiotics. Excluding two who were pregnant, all patients had imaging by intravenous urography (IVU), CT and DMSA during their admission. Urine samples were collected prior to treatment. Patients without IVU evidence of cortical scarring but with parenchymal defects on CT and/or DMSA underwent a repeat DMSA three or more months after the acute episode. Of the 164 patients, 142 were female. E. coli was found in 116 patients. Forty-six patients had an abnormality on IVU. Of the 106 patients without IVU evidence of cortical scarring, 59 had a defect on CT and/or DMSA. Late DMSA scans in 35 of these 59 patients showed a persistent abnormality in 77%. E. coli characteristics such as P-fimbriae and Type 1 fimbriae were not predictive of acute imaging abnormalities. Inhibition of E. coli growth by the addition of EDTA was highly predictive of acute CT and DMSA abnormalities with a sensitivity of 83.3% and a specificity of 82.8%. Acute pyelonephritis is often associated with acute CT and/or DMSA abnormalities which may evolve into renal cortical scars. Acute scan abnormalities can be predicted by the presence of E. coli which were susceptible to EDTA in culture. Late scarring could not be predicted by clinical features, response to treatment or antibiotic used. PMID- 7774072 TI - Age-related differences in susceptibility of males and females to end-stage reflux nephropathy. AB - Age-specific rates for entry into Australian maintenance dialysis and transplantation programmes show that reflux nephropathy is equally common as a cause of end-stage renal failure in males and females from 5 to 24 years, and over 75 years of age, but between 35 and 64 years renal failure due to this disease is significantly more common in women than men. PMID- 7774073 TI - Evaluation of a rapid specific ward based assay for creatinine in blood. AB - We have evaluated a dry reagent stick test for the quantitation of creatinine in plasma employing a whole blood sample. The assay was found to be specific for creatinine and correlated well (r = 0.993) with an established laboratory procedure. The precision found indicated that the method was suitable for use in the diagnosis and monitoring of renal disease. PMID- 7774074 TI - Mortality in patients receiving renal replacement therapy, a single center study. AB - We studied all patients receiving renal replacement therapy (RRT) in the Kennemer Gasthuis Dialysis Centre (Haarlem) during the period January 1st 1986 to January 1st 1991 in order to evaluate their mortality. Of the total number 205 patients, 76 had died in this period, 82 were still receiving RRT on December 31st 1991 and 47 had been transplanted. The most frequent cause of death was cardiovascular. Of the 76 patients who had died, 38 had requested cessation of dialysis. Of these, 26% had also a malignancy and 29% had irreversible brain damage (CVA, dementia). Compared to the expected mortality rate in the general population of The Netherlands, dialysis patients have a Standardized Mortality Rate (SMR) of 6.91 (95% Confidence Interval (CI) 4.72-9.54). Male patients had a SMR twice as high as females. Patients under age 50 had a SMR of 50.00 (95% CI 8.93-124.40) versus 50 and older 7.19 (95% CI 4.26-8.91). The SMR was similar for patients with and without cardiovascular comorbidity before entering RRT. A Kaplan-Meier plot showed a significant difference for not transplantable versus transplanted or transplantable patients, however SMR for these 3 groups revealed no difference. A Kaplan-Meier plot of patient survival of patients starting RRT after January 1986 (n = 114) showed a linear decrease of 20% yearly mortality. No gender difference was found. We conclude that 1. RRT is associated with high mortality, 2. SMR of young patients is higher than of the elderly and SMR of men is twice as high as SMR of women. Interestingly Kaplan-Meier survival plot did not reveal this difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774075 TI - Fibrillary glomerulonephritis and pulmonary hemorrhage in a patient with renal transplantation. AB - Fibrillary glomerulonephritis is an unusual kidney disease characterized by the deposition of immunoglobulins in a fibrillar pattern. Until recently it has been considered to involve the kidneys alone. We describe a patient who underwent renal transplantation and developed fibrillary glomerulonephritis with rapidly progressive renal failure and severe pulmonary hemorrhage two years and a half after transplantation. Nephropathy prior to transplantation was thought to be focal and segmental glomerulosclerosis. Diagnosis of fibrillary glomerulonephritis in renal allograft was confirmed by postmortem examination. 50% of the glomeruli with extracapillary crescents were observed on light microscopy. By immunofluorescence main deposition of IgA was detected in the glomerular capillar walls and the mesangium. Electron microscopy showed fibrillo reticular deposits in the same place. Lung histology showed both old and recent areas of alveolar hemorrhage. Granular staining for IgA was observed in the alveolar walls by immunofluorescence. Ultrastructural analysis of the lung made evident fibrillo-reticulary deposits in the interstitium, similar than those observed in the glomeruli. The presence of these deposits in both renal and pulmonary tissues indicates the possibility of systemic involvement in fibrillary glomerulonephritis. In our case it could be related to the recurrence of this glomerulopathy in renal allograft. PMID- 7774076 TI - Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients. AB - The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history. These patients had not been prescribed EPO as they had started hemodialysis prior to the clinical availability of EPO. There were 21 pairs without hospitalization and 46 pairs with at least 1 member of the pair experiencing hospitalization. Among the latter group, the median follow-up was 174 and 184 days for the EPO and control patients respectively. For all hospitalizations, those treated with EPO were hospitalized 15.3 days per year compared to 23.2 days for the control patients. The difference (EPO-control) was -7.9 days (95% CI: -21.0; 7.8) for all cause hospitalization. For hospitalizations due to cardiac, infectious disease and gastrointestinal disease, the differences were 1.6, 1.8 and 1.2 days favouring EPO treated patients. For hospitalizations related to vascular access complications, the difference was 0.9 days favoring the control group. All other causes favoured EPO treated patients by 4 days. There had been 58 hospitalizations in the EPO group compared to 97 in the control group. The mean duration of hospitalization was 8.0 days for the EPO and 9.6 for the control group. The direction and magnitude of the change in all cause hospitalization represents an improvement in morbidity and an important decrease in health resource utilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774077 TI - Bone marrow findings before and after treatment with recombinant human erythropoietin in chronic hemodialyzed patients. AB - The stimulating effect of rHuEPO on erythropoiesis has been shown in several studies, using bone marrow cell culture or animal models. To investigate the effect of rHuEPO on bone marrow findings in vivo, we studied the bone marrow cellularity, the myeloid: erythroid (M:E) ratio, an estimate of the number of megakaryocytes, any cytomorphologic or maturation abnormalities, and an estimate of the storage iron before and after 3 months of treatment with rHuEPO in 10 chronic hemodialyzed patients. Nine patients showed a slight or moderate decrease of erythropoiesis in bone marrow in comparison to normal bone marrow before rHuEPO treatment. The bone marrow cellularity was a mean of 28.5% and decreased in 8 out of 10 patients compared to normal values. However, megakaryopoiesis and granulopoiesis were normal. Three months of treatment with rHuEPO had increased erythropoiesis in all 10 patients, including one patient whose bone marrow proved to be normal erythropoiesis on baseline examination. The M:E ratio was significantly decreased from 4.0 +/- 1.2:1 to 2.4 +/- 1.1:1 (p < 0.005). The bone marrow cellularity was also increased in 9 patients, except in 1 patient whose specimen was inadequate for diagnosis, after 3 months of treatment with rHuEPO. On baseline examination of bone marrow, iron staining was undetectable in one, low in one, normal in 2 and high in 5 sections. According to grading, iron staining had decreased from 3.1 +/- 1.7 to 2.1 +/- 0.9 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774078 TI - Influence of recombinant human erythropoietin on hematological and hemostatic parameters with special reference to microhemolysis. AB - Twenty chronic hemodialysis patients with renal anemia (hematocrit < 25%) received recombinant human erythropoietin (40 IU/kg body weight 3 x weekly) intravenously after each dialysis. Prior to and at 4, 8 and 12 weeks after commencement of erythropoietin therapy, hematocrit together with hemostasis and microhemolysis parameters were determined. There were significant increases in hematocrit, platelet count and platelet retention, but a significant fall in the initial clearly prolonged bleeding time. Free plasma hemoglobin likewise increased. Conversely, lactate dehydrogenase, prothrombin time, fibrinogen, antithrombin III activity, protein C activity and protein S concentration were all unaltered. The positive effect on bleeding time and platelet retention is most probably caused by an increase in adenosine diphosphate due to the hematocrit-dependent rise in the blood shear stress via physiologic microhemolysis (raised free plasma hemoglobin). PMID- 7774079 TI - Glomerular filtration in patients suffering from reactive hypoglycemia. PMID- 7774081 TI - A case of unilateral renal cystic disease of a newborn. PMID- 7774080 TI - Gastric vascular ectasia in a chronic hemodialysis patient. PMID- 7774082 TI - Clinical and histological criteria defining the diagnosis of active chronic pyelonephritis in pregnancy. PMID- 7774083 TI - Patients with renal hypouricemia are prone to develop acute renal failure--why? PMID- 7774084 TI - Efficiency of hemodialysis therapy for a urea cycle defect in a neonate. PMID- 7774086 TI - From internal medicine to rheumatology and back: the example of mixed cryoglobulinemia. PMID- 7774085 TI - Pauci-immune crescentic glomerulonephritis and cutaneous vasculitis associated with anti-proteinase 3 antibody. PMID- 7774087 TI - Thrombocytopenia responsive to warfarin in a patient with systemic sclerosis- systemic lupus erythematosus overlap. AB - We report a patient with overlapping systemic sclerosis-systemic lupus erythematosus who developed refractory thrombocytopenia and recurrent thromboses. Coagulation and platelet labeling studies revealed that platelets were being consumed by the thrombus formation, and anticoagulation with warfarin dramatically increased the platelet count. This case report suggests that platelet consumption due to thrombus formation is one of the causes of thrombocytopenia in patients with rheumatic disease. PMID- 7774088 TI - Purine enzymes in rheumatoid arthritis. A clue to the prediction of the response to azathioprine? Review and hypothesis. AB - Azathioprine (AZA), a purine analog, is an effective agent in the treatment of rheumatoid arthritis (RA), but variability of response and sometimes life threatening side effects limit its use (1). The metabolism of AZA parallels the endogenous purine pathways. In this paper we review some general aspects of purine and thiopurine metabolism, their relation with various disease states and current knowledge of the influence of purine enzymes on the effects of AZA treatment. We suggest that intracellular purine enzyme activities determine the response to AZA treatment in patients with RA, and that a role for purine enzyme activities in the ethiopathogenesis of RA should be considered. PMID- 7774089 TI - Association of HLA-DR5 (DR11) with systemic sclerosis (scleroderma) in Mexican patients. AB - OBJECTIVE: To study the association between Major Histocompatibility Complex (MHC) haplotypes and systemic sclerosis (SSc) in Mexican mestizo patients. METHODS: Class I, II and III MHC antigens were determined in 41 Mexican mestizo patients with SSc, 113 of their first degree relatives, and 85 ethnically matched controls. The significance of differences between patients and controls was tested by chi-square analysis with Yates' correction. RESULTS: Frequencies of HLA DR5 and HLA-DRw52 were found to be higher in SSc patients compared to ethnically matched healthy controls (p = 0.007, RR = 3.31; 95% confidence interval: 1.3-8.3 and p = 0.04, RR = 2.4; 95% confidence interval: 1.0-5.7, respectively). Sequence specific oligotyping in DR5 positive individuals showed that 10 out of 41 patients had the DRB1*1104 subtype (24.3%) as compared to only 6 of the 85 healthy controls (7.0%) (p = 0.01, RR = 4.25). Subdividing patients according to their clinical features showed a significant increase of HLA-DR5 in diffuse (p = 0.013, RR = 3.89, 95% confidence interval: 1.27-12.0) and limited scleroderma (p = 0.0008), but not in the CREST syndrome. Segregation analysis obtained from the families showed that in the patients, DR5 was mostly part of the [HLAB35;DR5] haplotype as opposed to healthy controls. CONCLUSION: These data support the role of DR5 (DRB1*1104) in the genetic susceptibility to develop scleroderma in Mexican patients and also sustain the notion of genetically determined clinical subgroups of SSc. PMID- 7774090 TI - High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis. AB - OBJECTIVE: To assess the response to and safety of long term, high dose (> or = 1 mg/kg/week or > or = 15 mg/m2/week) methotrexate (MTX) administration, in a cohort of 21 children with longstanding, severe juvenile rheumatoid arthritis (JRA). METHODS: Children received MTX at an average weekly dose of 27 mg for a mean of 15.2 months. Outcome was assessed using a disease activity score based on changes in concomitant therapy, laboratory parameters, physician's global assessment, and radiologic evaluation. RESULTS: Seven patients (33%) improved, including one child who achieved complete remission, while 14/21 children (67%) did not benefit from high dose MTX. Subsequently, 6/14 (43%) of the non responders discontinued high dose MTX and began cyclosporine. Radiologic progression, regardless of clinical outcome, was documented in 10/15 (67%) of the patients. The drug was well tolerated despite mild gastrointestinal symptoms and transient liver enzyme elevation. CONCLUSION: The results of this open retrospective pilot trial suggest that high dose MTX is well tolerated, but that its role in the treatment of children with refractory JRA may be limited. Radiologic progression, despite improvement in the clinical status or in the laboratory parameters, supports the hypothesis that MTX acts as a potent antiinflammatory agent. PMID- 7774091 TI - Juvenile chronic arthritis in Costa Rica. A pilot referral study. AB - In order to adequately care for patients with chronic disorders and to properly allocate resources, the epidemiology of the underlying disease must be know. Proper population based studies involve substantial planning and educational programs, however. To prepare for such a study of pediatric rheumatic disorders, we performed a referral-based pilot study. During an eleven-month period pediatricians all over Costa Rica were asked to refer to us all new cases of possible rheumatic disorders among children less than 16 years of age, using the EULAR criteria for juvenile chronic arthritis. The children were evaluated at the National Children's Hospital. An annual incidence of 5.9 cases of all types of pediatric rheumatic diseases per 100,000 was found. Incidences of 5.4 per 100,000 children below 16 years of age and 6.1 for children below 12 years of age were observed for juvenile chronic arthritis (JCA). 77% of the JCA cases were of pauciarticular onset, and 23% were of polyarticular onset. No cases of systemic JCA were diagnosed. The female to male ratio was 3:2. Antinuclear antibodies were positive in 13% of the JCA cases, and IgM rheumatoid factor was found in 15% of the children. Chronic iritis was noted in only 2 cases; both were girls and both were ANA positive. The incidence found was low compared to population-based studies, but in the same range as hospital-based investigations. PMID- 7774092 TI - A possible linkage of HLA-DRB haplotypes with tiopronin intolerance in rheumatoid arthritis. PMID- 7774094 TI - Subcutaneous calcifications in diffuse idiopathic skeletal hyperostosis. PMID- 7774093 TI - Regression of amyloidosis with colchicine in familial Mediterranean fever in an Ashkenazi patient. PMID- 7774095 TI - Immunoglobulin production and eicosanoid precursors in patients with primary Sjogren's syndrome. PMID- 7774096 TI - On the utility of CD8 level assessment in the diagnosis of polymyalgia rheumatica/giant cell arteritis. PMID- 7774097 TI - Insufficiency fracture of the distal tibia mimicking arthritis in a rheumatoid arthritis patient. The possible role of methotrexate treatment. PMID- 7774098 TI - Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders. AB - OBJECTIVE: It is well established that connective tissue diseases such as systemic lupus erythematosus (SLE) are associated with a weak or absent acute phase response, although elevated serum interleukin 6 levels have been described. In this study, we have sought to correlate serum levels of IL-6 with standard laboratory and clinical assessments of disease activity in two connective tissue diseases, namely SLE and systemic sclerosis (SSc), and, for comparative purposes, rheumatoid arthritis (RA). METHODS: Serum IL-6 levels were determined by bioassay and also, in some sera, by immunoradiometric assay. They were compared with two inflammatory parameters, serum C-reactive protein (CRP) and plasma viscosity (PV), and with appropriate clinical measurements in the various patient groups, including BILAG in SLE, the skin score in SSc, and the Ritchie index in RA. RESULTS: Serum IL-6 (SeIL-6) levels were elevated in active SLE, SSc, and RA. This was poorly correlated with the acute phase response in SLE and SSc, but there was a strong relationship of SeIL-6 to disease activity in these conditions. In SLE, the BILAG disease activity index correlated best with SeIL-6 levels while there was only a weak relationship between CRP and IL-6, and no relationship between CRP and disease activity. In SSc there was a relationship of disease activity to SeIL-6 but not between SeIL-6 and either CRP or PV. In a small RA group there was a much stronger relationship of SeIL-6 to CRP and PV, as has been previously described. CONCLUSION: The determination of SeIL-6 may be a useful indicator of disease activity in those patients groups, including SLE and SSc, in which a normal acute phase response by the liver is often lacking. The mechanism underlying this hepatic impairment requires further investigation, but is clearly not due to a failure to generate the appropriate cytokine signal. Excessive local or systemic production of IL-6 in connective tissue diseases could play an important pathogenic role in these conditions, for example through stimulating autoantibody synthesis. PMID- 7774099 TI - A prospective study of the long-term efficacy and toxicity of low-dose methotrexate in rheumatoid arthritis. AB - OBJECTIVE: To determine the long-term efficacy and safety of weekly low-dose methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Fifty-one patients receiving MTX for RA were prospectively studied over a mean treatment period of 36 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 12, 24 and 36 months. RESULTS: The overall probability of continuing to take MTX was 80.3% at 12 months, 74.5% at 24 months, and 70.5% at 36 months. Of the 36 patients who completed 36 months of therapy, a significant improvement was noted compared to baseline in all of the clinical disease variables and acute phase reactants, with a steroid-sparing effect. There were no significant differences in these parameters between the 36-month visit and the 24- or 12-month visit. Adverse events occurred frequently (80.3%), but only 15.6% of the patients discontinued MTX permanently. Four patients (7.9%) withdrew due to a lack of efficacy. CONCLUSION: Our findings indicate that MTX remains effective over 36 months of therapy, with an acceptable toxicity profile. PMID- 7774100 TI - Abnormal T cell receptor V beta gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients. AB - OBJECTIVE: The aim of this study was to assess T cell receptor V beta-gene expression in the peripheral blood and synovial fluid of rheumatoid arthritis patients. METHODS: Cytometric analysis was performed on peripheral blood and synovial fluid lymphocytes from 12 patients using a restricted set of V beta specific monoclonal antibodies (to V beta 5.1-3, V beta 6.7 and V beta 8). In 5 patients the expression of the V beta 1 through V beta 20 gene families was also analysed, using a recently described method based on a one-side-specificity polymerase chain reaction coupled to reverse dot hybridization. RESULTS: Cytometric analysis failed to show any consistent difference in the expression of V beta 5, 6 and 8 between the two compartments on the one hand, or between the peripheral blood of normal individuals and patients on the other hand. The PCR/dot hybridization method did not demonstrate a significant difference in the V beta repertoires between peripheral blood and synovial fluid samples from arthritis patients. However, in all patients the V beta 6, 13 and/or 14 families were expressed to a high level, so that these families frequently represented over 40% of the V beta 1-20 repertoire in both compartments, instead of the approximately 20% seen in normal peripheral blood samples. CONCLUSION: We conclude that V beta 6, 13 and 14 are overexpressed in both the peripheral blood and synovial fluid of rheumatoid arthritis patients compared to normal samples. PMID- 7774101 TI - Undifferentiated arthritis in an early synovitis out-patient clinic. AB - OBJECTIVE: To describe the features of undifferentiated arthritis in an early synovitis out-patient clinic. METHODS: In a two-year prospective cohort study 320 patients with rheumatic symptoms of less than one year were investigated in an early synovitis out-patient clinic. Besides the clinical parameters, an intensive laboratory program was performed, including routine blood and serum parameters, immunological investigations (CRP, IgG,A,M,C3C4,RF,ANA, DNA, HLA B-27), and a microbiological program to search for reactive arthritis-inducing infections. RESULTS: 217 patients had inflammatory rheumatic diseases, of whom only 100 (46%) could be given a definite diagnosis, whereas 117 (54%) were considered as having undifferentiated arthritis (UA). Patients with UA had a mean age of 41 +/- 15 years, the sex-ratio was 1.8:1.0 (f/m), joint manifestations were oligoarticular in 68%, monarticular in 14%, and polyarticular in 18%. Rheumatoid factor was positive in 17%, HLA-B27 was found in 27%, and 21% of the patients had a history of recent infection. Follow up over 26 (range 4-38) months of 28 (24%) patients with UA revealed complete remission in 15 patients (54%), while 10 patients (36%) had further UA with partial remission, unchanged activity or progressive disease, and only 2 (7%) developed rheumatoid arthritis (RA) and 1 (4%) was diagnosed as having ankylosing spondylitis. CONCLUSION: Most patients with early synovitis followed at our clinic remain unclassified with a good prognosis. PMID- 7774102 TI - Takayasu's arteritis in Italian patients. AB - OBJECTIVE: To evaluate the clinical features, angiographic findings and evolution of Takayasu's arteritis in Italian patients. METHODS: Retrospective analysis of the case records of 27 Italian patients with Takayasu's arteritis, all meeting the 1990 ACR criteria for classification of this vasculitis, with a median disease duration of 9.5 years. RESULTS: The patterns of arterial involvement and the frequencies of systemic and specific symptoms were similar, with some exceptions, to those reported in the literature. In our patients weight loss was rare, the incidence of respiratory symptoms and seizures was low, and no clinical manifestations of intestinal involvement were reported. All of the patients were treated with antiplatelet or anticoagulant medications, and 14 were also treated with corticosteroids and immunosuppressants; a stabilization of the vascular involvement was seen in most of them. Thirteen patients underwent surgery, and 5 had percutaneous transluminal renal angioplasties. Five pregnancies were observed, without complications. Two patients died, one after an angiographic evaluation and one for reasons unrelated to the disease. CONCLUSIONS: Takayasu's arteritis is heterogeneous in presentation, evolution and response to therapy. In our series of patients the disease seems to have showed a more favorable course than that previously reported. This can be attributed to the effectiveness of therapy, but also, at least partially, to the better prognosis that the disease seems to have for Western than for Eastern subjects. PMID- 7774103 TI - Modified expression of c-Fos and c-Jun proteins and production of interleukin-1 beta in patients with rheumatoid arthritis. AB - OBJECTIVE: To examine the relationship between the expression of c-Fos and c-Jun proteins and the METHODS: The expression of c-Fos and c-Jun proteins and the production of IL-1 beta in the PBMC of 11 patients with active RA was determine by Western blots and ELISA techniques, respectively. RESULTS: The spontaneous expression of c-Fos protein and the production of IL-1 beta was higher in RA patients. Under LPS treatment, the PBMC of both RA patients and healthy subjects produced similar high levels of IL-1 beta without any significant changes in the expression of c-Fos and c-Jun proteins. By contrast, PMA-induced production of IL 1 beta was impaired in RA patients and was preceded by the disregulated expression of c-Fos and c-Jun proteins when compared with healthy donors. CONCLUSION: It can be postulated that in some RA patients the spontaneously high production of IL-1 beta may be associated with the up-regulated expression of c Fos protein in PBMC. On the other hand the impairment of IL-1 beta production in RA induced by the PKC-dependent pathway, may be related to disturbances in c-Fos and c-Jun protein expression. This dysfunction seems to be compensated by some unknown mechanisms implicated in LPS signalling, which is known to involve not only the PKC-mediated pathway. PMID- 7774104 TI - A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis. AB - OBJECTIVE: To examine the value of calprotectin, a major granulocyte protein with bactericide properties, as an inflammatory marker in patients with reactive arthritis. METHODS: Twenty-five patients with Chlamydia-induced and 27 patients with enterobacteria-induced reactive arthritis were analysed. At the first visit and after 3, 12, 24, 52 and 104 weeks, calprotectin concentrations were measured in plasma and when possible, in synovial fluid. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were analysed and clinical assessments of disease activity were performed. RESULTS: Of the inflammatory markers, the plasma calprotectin concentrations were the first to normalize during recovery. Calprotectin concentrations in the plasma were highly correlated with CRP and ESR, and calprotectin was found to have high correlation coefficients with the clinical assessments of disease activity. High calprotectin concentrations were found in the synovial fluid. CONCLUSION: The high correlations between calprotectin in plasma and clinical and laboratory markers of inflammation, as well as the rapid normalization following clinical improvement, demonstrate that calprotectin may be used as an inflammatory marker in patients with reactive arthritis. PMID- 7774105 TI - Fetal outcome in women with primary Sjogren's syndrome. A retrospective case control study. AB - OBJECTIVE: To study fetal outcome in women with primary Sjogren's syndrome (SS) compared to that in women with systemic lupus erythematosus (SLE) and healthy women, and to study the possible association of fetal loss with anticardiolipin antibodies (aCL) and antibodies to SS-A/Ro and SS-B/La in women with primary SS. METHODS: A retrospective analysis of the fetal outcome in 55 pregnancies in 21 patients with primary SS compared to that in 100 pregnancies in 42 patients with SLE and 94 pregnancies in 42 healthy women matched for age, parity and the onset of the autoimmune disease with respect to pregnancy. IgG-, IgM- and IgA-aCL were determined by a cofactor-dependent ELISA and antibodies to SS-A/Ro and SS-B/La by ELISA using human recombinant antigens and affinity-purified antigens. RESULTS: Of all the 55 pregnancies in patients with primary SS, 8 (15%) occurred after the onset of primary SS symptoms. Eleven (20%) of the 55 pregnancies ended in fetal loss. The relative risk (RR) for fetal loss in patients with primary SS was 2.7 (95% CI 1.1-6.5; p = 0.023), and after the exclusion of the patient with four spontaneous abortions it was 2.0 (0.7-5.3; p = 0.18). In SLE the level of risk was 2.2 (0.9-5.0; p = 0.065). Fetal loss in patients with primary SS was not associated with elevated levels of anticardiolipin antibodies (aCL) or autoantibodies to SS-A/Ro or SS-B/La. Newborns of mothers with primary SS were not more premature or growth retarded than newborns of healthy women, but the absolute and the relative birth weights of the newborns of mothers with SLE was significantly lower than in healthy controls (P < 0.001 and P < 0.0001, respectively). CONCLUSION: We conclude that the majority of pregnancies in women with primary SS occur before the onset of the disease and that these women have an increased risk of fetal loss, which is not associated with elevated levels of ACL or antibodies to SS-A/Ro or SS-B/La. The risk of fetal loss in primary SS is similar to that in women with SLE, but fetal growth retardation appears to be more common in SLE than in primary SS. PMID- 7774106 TI - Induction of anti-DNA antibodies in non autoimmune mice by immunization with a DNA-DNAase I complex. AB - Recent studies suggest that anti-DNA antibodies may arise from the immune response to a complex of DNA and a DNA-binding protein. One of the protein targets frequently recognized by anti-DNA antibodies is the enzyme DNAase I. To investigate the possible role of DNAase I in the induction of anti-DNA antibodies, we immunized mice with a complex of DNA and DNAase I. Mammalian double strand DNA was crosslinked with DNAase I by ultraviolet light (UV) treatment and emulsified in complete Freund's adjuvant. BALB/c mice were immunized at the base of the tail with the DNA-DNAase complex, boosted after 2 weeks with the immunogen in incomplete adjuvant and bled one week after the boost. Control mice received UV treated DNA in adjuvant. In one-third of the mice immunized with the DNA-DNAase complex, IgG anti-DNA antibodies were detectable in serum; the antibodies reacted with single and double strand DNA. No anti-DNA response was elicited by immunization with DNA alone. These data show that immunization with a DNA-DNAase complex can induce anti-DNA antibodies in non autoimmune mice strains and suggest that DNA-binding proteins may act as carriers in the immune response that leads to anti-DNA antibody production. PMID- 7774107 TI - The effect of sleep and nocturnal movement on stiffness, pain, and psychomotor performance in ankylosing spondylitis. AB - OBJECTIVE: This study was carried out in order to assess whether AS patients are adversely affected by a "good" night's sleep accompanied by little nocturnal movement. METHODS: Objective and subjective nocturnal movement, flexibility, stiffness, pain and psychomotor performance were measured in 22 subjects, 11 with ankylosing spondylitis and 11 controls. RESULTS: A better sleep integrity with little nocturnal movement was related to a decrease in lumbar flexibility. Difficulty in awakening and feeling tired and clumsy in the morning correlated with stiffness. Pain was correlated with a subjective difficulty in getting to sleep and a worse quality of sleep, but was also correlated with less objective sleep disruption. In the control group a better sleep integrity was correlated with an overnight decrease in psychomotor performance. In the spondylitic group a significant increase in performance occurred. Stiffness and pain did not correlate with performance. CONCLUSION: Sleep in ankylosing spondylitis differs from sleep in normals. PMID- 7774108 TI - Diverticulosis--a primary cause of life-threatening complications in rheumatoid arthritis. AB - OBJECTIVE: To assess the role of complicated diverticular disease as a cause of death in rheumatoid arthritis (RA). METHODS: In 1989 there were in Finland 1,666 deaths in subjects entitled to specially reimbursed medication for RA under the nationwide sickness insurance scheme. A retrospective clinical study was performed on these cases. RESULTS: In 12 subjects, four males and eight females, the underlying cause of death was diverticular disease; the expected number was two. The mean age at death was 74 years in males and 80 years in females. The duration of RA ranged from 4 to 22 years (mean 13 years). In none of these cases was the death connected in the death certificate to RA or its treatment, yet all the subjects had been taking antirheumatic medication, usually two or three different drugs, at the time of death. CONCLUSION: Complicated diverticular disease, probably related to antirheumatic medication, is a more important cause of death in patients with RA than is generally recognized. PMID- 7774109 TI - Microvascular capillaroscopic abnormalities in rheumatoid arthritis patients. AB - Microvascular circulation was investigated by nailfold capillaroscopy in 32 patients affected by rheumatoid arthritis (RA). In all the patients elongated and tiny capillaries as well as tortuousity were the main shape abnormalities of the capillary loops. Higher subpapilar venous plexus (SPVP) visibility was evidentiated in patients presenting antinuclear and anti-RANA antibodies. No differences in the capillaroscopic pattern were found between rheumatoid factor positive and rheumatoid factor negative patients. In conclusion, elongated and tortuous capillaries seem to be the main alterations in RA, although they are not specific to the disease and are not correlated with the presence of rheumatoid factor. Higher SPVP visibility may be an expression of the endothelial damage induced by antinuclear antibodies in vessel walls. PMID- 7774110 TI - Effects of fish oil on plasma fibrinolysis in patients with mild rheumatoid arthritis. AB - As rheumatoid arthritis (RA) patients have been shown to have impaired plasma fibrinolysis and fish oil has been suggested to be useful for RA, this study investigated the effects of fish oil on fibrinolytic parameters in patients with RA. Forty-five RA patients were randomised to receive either fish oil (1.7 gm eicosapentaenoic acid and 1.1 gm docosahexaenoic acid/day) or placebo treatment for at least 6 months. Plasma levels of fibrinogen, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) activity were measured at 3 month intervals. In the fish oil treatment group, plasma levels of fibrinogen and t-PA activity were reduced at 6 months when compared with baseline [fibrinogen: 3.2 (2.85-3.53) milligrams vs 3.89 (3.56-4.22) milligrams, mean (95% confidence intervals for mean), p < 0.02; t-PA activity 1.4 (1.01-1.78) units/ml vs 1.94 (1.55-2.33) units/ml, p < 0.01]. No significant changes in plasma PAI activity were seen during the treatment period in these patients. Placebo treatment did not significantly alter the plasma levels of fibrinogen or t-PA and PAI activity. In conclusion, fish oil supplementation does not appear to produce an improvement in plasma fibrinolysis. Indeed, plasma fibrinogen levels and t-PA activity were reduced. This could be due to an effect of fish oil on acute phase protein production. Alternatively, as t-PA is produced on an "on demand" basis, its reduction may be related to the lowering of fibrinogen levels following fish oil therapy. PMID- 7774112 TI - Schnitzler's syndrome (urticaria and macroglobulinemia) dramatically improved with corticosteroids. AB - The authors report the case of a 65-year-old man who had an evolving case of Schnitzler's syndrome with lytic bone lesions which was unresponsive to several drugs, and which dramatically improved with small quantities of corticosteroids. Schnitzler's syndrome, first described in 1974, is defined by chronic non pruritic urticaria, osteocondensation, and monoclonal IgM dysproteinemia without features of lymphoproliferative disease, and is associated with fever, deterioration of the general health and biological signs of inflammation. Only 22 cases of Schnitzler's syndrome have been reported hitherto and there is no known effective treatment, H1 and H2 blockers, dapsone, colchicine, chloroquine, cyclophosphamide, chlorambucil and azathioprine having proven useless in the few patients treated. Corticosteroids may be effective, however, especially against the urticaria. PMID- 7774111 TI - Ectopic calcinosis possibly due to 1 alpha (OH) vitamin D3 in a patient with systemic lupus erythematosus. AB - A 30-year-old woman with systemic lupus erythematosus (SLE) developed ectopic calcinosis. She had been receiving prednisolone since 1980 with the addition of vitamin D3 in 1986. Despite this therapy, her renal function had gradually deteriorated. Right gonalgia was noted in September 1991. X-ray findings revealed calcinosis of the arteries of the femur, poplitea, cubitus, hands, and feet. Her finger pads and joint sacs were also involved. Calcinosis seen in SLE has only rarely been reported, and that observed in association with vitamin D intoxication or arteriosclerosis has a different distribution of calcium deposits. The use of vitamin D3 in our patient with renal disability may have induced calcinosis with a unique distribution. PMID- 7774113 TI - Severe lupus with infectious thyroiditis and lethal cardiomyopathy. AB - Clinical cardiomyopathy is an uncommon complication of systemic lupus erythematosus (SLE) and intracavitary thrombosis is rare. We describe a patient with active SLE who developed rapidly progressive cardiomyopathy, the fatal course of which was complicated by an intracavitary thrombus. Repeat cardiac echography studies and the endomyocardial biopsy proved to be helpful in diagnosing the lupus myocarditis and aided the regulation of therapy. Furthermore, the patient presented an acute suppurative thyroiditis never before described, to our knowledge, in SLE. PMID- 7774114 TI - [Causative factors and neurological diseases]. AB - Considering the pathogenesis of neurological diseases, it is important to determine causative factors directly affecting the nervous system. We discussed here some neurological diseases induced by exogenous agents (thallium, organic phosphorus, organic solvents, acrylamide) and by "endogenous" agents (Krabbe disease, Alzheimer disease, familial amyloidotic polyneuropathy). In diseases by exogenous toxic agents, it is not very difficult to find the toxic factors. However, because a single agent can induce a variety of clinical symptoms, we should consider the dose of the agents, the toxic mechanisms and the susceptibility of tissues or organs. In endogenous diseases, causative agents are either toxic factors or the substances inducing mechanical injury. Endogenous toxic agents are usually produced by affected cells themselves. In the case of the substances inducing mechanical injury, the pathogenesis is more complex. The structure of the abnormal agents and tissue susceptibility should be considered. PMID- 7774115 TI - [The genetic manipulation and the brain research]. PMID- 7774116 TI - [Molecular analysis and pathophysiology of genetic leukodystrophies]. AB - The elucidation of the molecular genetics in genetic leukodystrophies is rapidly progressive. In 1993, genes responsible for adrenoleukodystrophy (ALD), globoid cell leukodystrophy and Canavan disease have been cloned. In this symposium, I will focus only on ALD because of the limitation of space. ALD is an X-linked recessive demyelinating disease of childhood. Adrenomyeloneuropathy (AMN) is a clinical variant of ALD. In both types of the disease, very long chain fatty acids accumulate in the body fluid and tissues of the patient. This finding suggests that there is a metabolic defect in the beta-oxidation in the peroxisome, but the primary defect has been unknown. In 1993, Mosser et al. reported a putative gene for ALD. According to the report, we obtained the cDNA from HeLa cells. Using the cDNA as the probe, we analyzed the expression of the gene in various samples of human and murine tissues. On northern blot analysis, mRNA of the gene was detected in all the tissues examined, and the amount and size of the mRNA were similar among all the tissues. We also examined the DNA and mRNA in 6 patients with ALD or AMN. On southern blot analysis, we could not detect large deletion in all the patients, while in northern blot analysis, mRNA was not detected in one patient (#163). The nucleotide sequence of mRNAs of the remaining 3 of 5 patients depicted different missense point mutations. The mutations were localized in the C-terminal regions of the gene, which are evolutionally conserved among ATP-binding protein superfamily, thereby suggesting that the mutations cause functional defect in the ALD protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774117 TI - [Molecular genetics in Creutzfeldt-Jakob disease]. AB - Recent molecular genetic studies revealed that human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to the distinct type of prion diseases. We report herein that it is useful to classify prion diseases into Creutzfeldt-Jakob disease (CJD) type or Gerstmann-Straussler syndrome (GSS) type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 105, codon 129, codon 145 and insertional mutations belong to the GSS type, while the wild type PrP and the variants including codon 180, codon 200, codon 210, and codon 232 mutations belong to the CJD type. The CJD type prion diseases showed a rapidly progressive dementia, myoclonus, and periodic synchronous discharges in the electroencephalogram, and showed diffuse gray matter PrP accumulations including the synaptic structures in the pathological findings. The GSS type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposit in the central nervous system influences the clinical and pathological aspects of prion diseases. PMID- 7774118 TI - [Expansion of triplet repeat and neurodegenerative disorders]. AB - Recent studies on human genetic analysis have revealed that there is hitherto unknown category of genomic abnormality in human genetic diseases; an abnormal expansion of trinucleotide repeat. For example, Huntington's disease is caused by the CAG expansion to more than 40 in IT15 gene Up to the present, we have 7 disorders which are revealed to be apparently caused by the triple repeat expansion: fragile X syndrome (two types), myotonic dystrophy, Huntington's disease, spinocerebellar atrophy type 1, dentatorubropallidoluysian atrophy and bulbo-spinal muscular atrophy. In this symposium, I would like to show first a clear inverse relationship between a length of CAG repeat and the age at onset in each Huntington's disease patient in Japan. Next, we would like to review and discuss on 1) the possible role of normal trinucleotide repeat in human gene, 2) the mechanisms for expansion of triplet repeat and for instability of the repeat length, and 3) the actual mechanism for neuronal cell death related to the expansion of triplet repeat. PMID- 7774119 TI - [Molecular basis of heterogeneities of clinical presentation of dentatorubral pallidoluysian atrophy (DRPLA)]. AB - Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder affecting primarily dentatorubral as well as pallidoluysian atrophy. From a view point of clinical genetics, DRPLA is characterized by prominent anticipation and considerable heterogeneities in its clinical manifestations. Given the fact that unstable CAG repeat expansion is the causative genes for Huntington disease and spinocerebellar ataxia 1, in which anticipation and parental bias of transmission of the severest form are present, we hypothesized that DRPLA might be caused by unstable expansion of a gene containing a CAG repeat. By screening published genes containing CAG repeats, were able to identify the gene for DRPLA located on the chromosome 12. All the DRPLA patients had expanded CAG repeats, and furthermore, there is a good correlation between the degree of CAG repeat expansions and the ages of onset. There are also good correlation in the ages of onset of each of the neurological of manifestations including myoclonus, choreoathetosis, epilepsy, dementia, and psychiatric symptoms. We concluded that the unstable expansion of the CAG repeat in the DRPLA gene is intimately involved in the pathogenesis of DRPLA. PMID- 7774120 TI - [CTG-repeat in myotonin protein kinase]. AB - Myotonic dystrophy (DM) is one of the most common inherited neuromuscular diseases in adults with a global incidence of 1 in 20,000 individuals. DM is an autosomal dominant disorder characterized primarily by myotonia and progressive muscle weakness. DM has unique genetic feature of anticipation, that is, increasing disease severity from generation to generation. DM candidate gene encodes a protein kinase (myotonin protein kinase; MtPK) expressed ubiquitously, and nearly all cases of DM displayed expansion (about 100 to 1,000) of the CTG repeat in the 3'-untranslated region, whose repeating number is in proportion to the severity of the condition. The physiological functions, however, of MtPK and the triplet repeat expansion are not yet clear. Thus, to elucidate the molecular mechanism of DM and for therapy of DM at last, we started biochemical analysis of MtPK and molecular biological study of CTG repeat. First of all, we have cloned a full length cDNA for MtPK, which encodes 625 amino acid residues and contains 5 repeats of CTG. Detailed structural analysis of MtPK and expression study of MtPK using the cDNA were performed, and physiological function of MtPK is discussed based on the results. PMID- 7774121 TI - [Intractable epilepsy--neurophysiological evaluation and indication for surgical treatment]. AB - Medically intractable epilepsy, defined as the clinical attacks occurring at least once a month in spite of appropriate antiepileptic drug treatments, is one of the commonest disorders in the clinical neurology. Since surgical treatment of epilepsy is successful in selected patients, it is most important to delineate the epileptogenic focus and functions of adjacent cortical areas as precisely as possible. Recent advances in electrophysiology, magnetoencephalography, magnetic resonance imaging (MRI), functional imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have enabled us to elucidate the epileptogenic focus noninvasively without involving the conventional invasive EEG recording techniques. We evaluated 37 patients with intractable partial seizures by using prolonged video/EEG monitoring with sphenoidal or T1/T2 electrodes. MRI, ictal and interictal SPECT for blood flow measurement and interictal FDG-PET for glucose metabolism. Among 20 patients with intractable epilepsy who had a single ictal focus, PET, ictal SPECT and MRI findings were correlated with the ictal EEG finding with the concordance rate of 100, 86 and 75%, respectively. If all of those findings were convergent upon a single focus, then the surgical treatment with intraoperative corticography is most likely effective without employing any invasive recording. If those findings were divergent, then the invasive evaluation will be indicated. PMID- 7774122 TI - [Basic and clinical approaches for surgical treatment of intractable epilepsies]. AB - Recent reports demonstrated that patients with medically intractable epilepsy were benefited with surgical treatments. Even in pediatric patients, early surgery is effective not only in seizure control but also in verbal, intelligent and social outcomes. In the present study, basic and clinical approaches in the treatment of intractable epilepsies were studied. In chronic cat model of intractable temporal lobe epilepsy induced by a microinjection of kainic acid, temporal cortical excision with amygdala focus resection or focus and hippocampal resections were examined by means of microsurgical technics. The cats with amygdala focus resection demonstrated spontaneous hippocampal seizures while cats with focus and hippocampal resection did not show seizures in the long time course after the surgery. In a cat model of cortical focal seizures, multiple subpial transection(MST) was examined. The cortical seizures, induced by a microinjection of kainic acid into unilateral sensori-motor cortex, were suppressed immediately after the MST. Postoperative course was uneventful and seizure was not recurred. However, pathological study demonstrated subpial scar formation at the site of MST in the sensori-motor cortex. In 38 patients with medically intractable epilepsies, surgical treatments were performed in the Department of Neurosurgery. Asahikawa Medical College. The site of the epileptogenic lesion was studied with Video-EEG longterm monitorings, Neuro imagings with CT, MRI, interictal SPECT and/or ictal SPECT. At the surgery, intraoperative electrocorticograms(ECoGs) were monitored under light neuroleptanalgesia in order to localize epileptic focus. Seizure free rate with or without postoperative medication was 72%. Remarkable improvement was observed in 7 patients (18%), but, 4 patients (10%) did not show any improvement. PMID- 7774123 TI - [Physiological bases of involuntary movement]. AB - Recent physiological, anatomical and neurobiological works on the basal ganglia give us clues for our understanding of the mechanisms of generation of involuntary movement. These are characteristic neuron circuit of the basal ganglia and signal content of the information transferred through the basal ganglia circuit. Efferent signals mediated by the striatal projection neurons are fed to either the internal segment (GPi) or external segment (GPe) of the globus pallidus or substantia nigra pars reticulata (SNr). Projection neurons of the striatum, GPe, Gapital and SNr are all inhibitory in their action, while those of the subthalamic nucleus (STN) are excitatory. Therefore, projection from the striatum to the GPi or SNr (direct path), output nucleus of the basal ganglia, would produce facilitatory effects on the target of the basal ganglia output through disinhibition. On the other hand, projections of striatum-GPe-STN-GPi pathway (indirect path) would produce active inhibition of the target. GPi activity of monkey rendered Parkinsonism by MPTP is abnormally high and activity of GPe is lower than that before MPTP application, while the GPi activity of STN lesioned monkey showing limb dyskinesia (hemiballismus) is much lower than normal animal. These observations suggest it is essential to maintain adequate level of basal ganglia inhibitory output for proper muscle tone and stable performance of movement. Indirect pathway and STN system may play an essential role in the stabilization of output level of basal ganglia. PMID- 7774124 TI - [Involuntary movements mechanism by reference to stereotactic surgery]. PMID- 7774125 TI - [Cervical myelopathy from an aspect of a neurological surgeon]. AB - More than 65 per cent of intramedurally tumors and intradural extramedurally tumors were located in cervical region. They enact a cause of cervical myelopathy. A special attention should be paid to solitaly intramedurally vascular malformations, when the patients show an acute progressive myelopathy. In very rare cases of syringomyelia, intramedurally tumors such as hemangioblastoma or ependymoma could be found, so that enhanced MRI or angiography should be done if necessary. In cases of a herniated disc, cervical spondylosis and OPLL, the distance between articulo-pillar line and spinolaminal line must be measured. If the distance of both lines is near or the same, that means narrow cervical canal. In rare cases the form of the vertebral body is round. This is a rare cause of a type of narrow canal. PMID- 7774126 TI - [Visual information processing in humans]. AB - Recent advances in parallel information processing of primates and humans have been reviewed. First, I review what is known about physiology and anatomy of the primate visual pathways. Several lines of evidence suggest that the primate visual system consists of the parvocellular (P) and the magnocellular (M) pathways. M-system originates from the A retinal ganglion cells that project to the visual cortex (V1) via the magnocellular layers of the lateral geniculate nucleus (LGN). This system plays an important role for motion and stereopsis. P system derives from the B retinal ganglion cells that project to V1 via the parvocellular layers of the LGN. This system shows selectivity for color vision and form perception. Second, I focus on the information processing of the human visual pathways. Psychophysical evidence suggests that there are also P and M systems in humans. However, there have been few electrophysiological studies which intend to separate the responses specific to P and M systems in human visual evoked potentials (VEPs). Based on the physiological distinctions between P and M systems, the use of isoluminant color patterns and apparent motion display allows us to evaluate P and M systems, respectively. PMID- 7774127 TI - [Magnetoencephalography (MEG) and functional brain mapping]. PMID- 7774128 TI - [Evoked potentials]. AB - Recent advances of evoked potentials, mainly pain-related somatosensory evoked potentials following CO2 laser stimulation (pain SEPs), were summarized. A small negative and a large positive potential, the N240-P340 and the N300-P400 following the hand and the foot stimulation, were identified in normal subjects. Conduction velocity of the A delta fibers and the spinothalamic tract was approximately 10 m/sec. Pain SEPs were significantly decreased in amplitude and the marked pain relief was induced by vibration applied to the area where laser stimulation was applied. This finding was compatible with the gate control theory. Active and passive movements of the limbs remote from and adjacent to the stimulated area significantly decreased pain SEPs in amplitude. This indicated the particular interactions between pain perception and movement-related cortical activities taken place in some areas of the brain. The theory, diffuse noxious inhibitory controls (DNIC) proposed by Le Bars et al., was also confirmed by pain SEPs. Pain SEPs were useful in clinical testing. Pain SEP findings showed a significant correlation with the clinical impairment of pain sensation, and the subclinical lesions of the ascending pathways of the painful sensation were detected by pain SEPs. PMID- 7774129 TI - [Transcranial magnetic stimulation]. AB - The technique of transcranial magnetic stimulation of the motor cortex is a new neurophysiological examination of the central motor pathways. In clinical application a reduced MEP/M wave amplitude ratio had a higher correlation with hyperreflexia than did a delayed MEP onset latency. The inhibitory period (IP) which is a transient suppression of muscle action potentials following motor evoked potentials (MEP) by magnetic cortical stimulation is caused primarily by inhibitory process in the motor cortex, because the duration of IP did not depend on the amplitude of MEPs, MEP distribution over the motor cortex or severity of voluntary contraction. Furthermore, the IP was shorter and the amplitude of MEP was increased when ipsilateral motor cortex stimulation to the thenar muscle preceded the contralateral cortex stimulation. C response in a patient with familial essential myoclonus was significantly suppressed by the magnetic stimulation of the sensory cortex locally and during the IP. The uncrossed pyramidal tract was proved by motor cortex stimulation in a patient with hemorrhage in the right thalamus and internal capsule who showed a right hemiparesis. The enhancement of cortical SEP amplitudes (P23 and N30) were noted when the median nerve was stimulated at 50 msec following magnetic stimulation over the sensory cortex locally. SEPs by twin coil stimulation at thoracic and lumbar root levels are useful in detecting the lesions of spinal cord or roots. Sympathetic skin responses and sudomotor potentials are recorded easily by the neck magnetic stimulation, and are useful method for evaluating sympathetic nerve function. PMID- 7774130 TI - [The nervous system involvement in human retroviral infection]. AB - Human T-lymphotropic virus type I (HTLV-I) is a pathogenic retrovirus associated with a chronic progressive myelopathy, termed HTLV-I-associated myelopathy (HAM). A chronic inflammatory process has been implicated in HAM by a pathological study, but the exact mechanism still remains to be elucidated. Our quantitative polymerase chain reaction study indicated that the large increase in the HLTV-I proviral DNA in peripheral blood is associated with the development of HAM. The nucleotide sequence analysis of HTLV-I in central nervous system (CNS) tissue of HAM patients revealed that the sequences of HTLV-I genome were heterogenous in all cases, and that the pX-defective mutants were found frequently in the CNS. Thus, HTLV-I exists as quasispecies in vivo, as shown in the case of human immunodeficiency virus. It is possible that the HTLV-I pX microvariants contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication. PMID- 7774131 TI - [Free radicals and neural cell damage]. AB - Free radicals are species containing unpaired electron, such as superoxide, hydroxyl radical and nitric oxide. The non-radical hydrogen peroxide is easily converted to the free radical during metabolism. These free radicals and hydrogen peroxide are constantly generated in the human and animal bodies and removed by antioxidant defences. Excessive production of free radicals can result in tissue damage, which mainly involves generation of hydroxyl radical and other oxidants in the presence of iron. The brain tissue contains large amount of unsaturated fatty acids and catecholamines, which are thought to be target molecules for free radical-induced peroxidation and neural cell damage, and such free radical induced cell damage appears to play a major role in the pathogenesis of many neurological diseases. PMID- 7774132 TI - [Superoxide formation and lipid peroxidation by the mitochondrial electron transfer chain]. AB - Isolated mitochondria supplemented with succinate or NAD(+)-linked substrates generate hydrogen peroxide (H2O2) in State 4 and the generation is enhanced by antimycin A, an inhibitor of the respiratory chain. Superoxide is a stoichiometric precursor of mitochondrial H2O2 because the ratio of O2-/H2O2 generation rates is close to 2.0 and is generated by an autoxidizable component in the NADH dehydrogenase and the ubiquinone-cytochrome b site. Lipid peroxidation is a free radical-mediated degradation of polyunsaturated fatty acids. Lipid-peroxidation reactions by bovine submitochondrial particles are supported by NADH or NADPH in the presence of ADP-Fe3+ chelate. Electrons from NADH are supplied to the reactions from a component between the substrate site and the rotenone-sensitive site of the NADH dehydrogenase. The peroxidation is dependent on the rate of electron input into the respiratory chain and on the concentration of reduced ubiquinone. Alteration of inner-membrane components and damage to electron-transfer activities of submitochondrial particles are induced by lipid peroxidation. 1-Melhyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in submitochondrial particles, indicating that the oxidative stress induced by MPP+ may potentiate its toxicity in dopamine neurons. PMID- 7774133 TI - [Electrodiagnosis of neuromuscular diseases--a syndrome of monomelic amyotrophy with spinal hemiatrophy, anti-GM1 antibodies and abnormal F-waves (MASH)]. AB - Electrodiagnosis rests upon sound anatomical and physiological bases of the peripheral nervous system, which are utilized for the dynamic process of differential diagnosis. If clinical and electrophysiological findings do not conform to any of the previously known diseases, there may be a chance of identifying a new entity. As an example, we report nine Japanese patients with unilateral atrophy of the distal upper limb and the cervical cord. Symptoms typically began insideously in young adulthood, progressed for a few years and then stabilized. Distribution of the muscle weakness usually corresponded to the territories of a few peripheral nerves, although not accompanied by sensory deficits. Serum anti-GM1 IgG antibodies were elevated in 6 out of 9 patients. Electrophysiological testings disclosed absent or delayed F-waves in the nerve involved. No long tract signs of the cord were demonstrated, although the spinal cord atrophy was extensive in some patients. Three showed partial clinical improvement after cyclophosphamide therapy or intravenous immunoglobulin. These findings may suggest that this entity is immune-mediated as in multifocal motor neuropathy, with its blunt of immune attack directed not only to peripheral motor nerves but also to spinal motor neurons. PMID- 7774134 TI - [Radiological imaging of the central nervous system]. AB - The radiological evaluation of central nervous system has been dramatically altered by the advent of MR imaging. MR imaging is a versatile modality that has been applied in almost all kinds of disorders in the brain, spinal cord and the surrounding structures. However, there are some limitations, such as low detectability of subarachnoid hemorrhage or calcifications, difficulty in visualization of bony details, and various kinds of artifacts. On the other hand, there have also been considerable technical advances in other imaging modalities, such as spiral CT, doppler US, etc. With the continuous advance in each imaging modality, their roles and the strategy in the diagnosis of disorders in central nervous system will be changed. In this review, the present status and current roles of various imaging modalities, such as plain X-ray, CT, MR imaging, nuclear medicine, ultrasound, angiography and myelography, are discussed. PMID- 7774135 TI - [Muscle pathologic diagnosis--mechanism in muscle fiber degeneration]. AB - In various neuromuscular diseases, the most significant muscle degeneration is muscle fiber necrosis as seen in Duchenne muscular dystrophy (DMD). A certain membrane instability is probably responsible for muscle fiber necrosis, because defects in membrane proteins have been proposed to associate with progressive muscular dystrophies including dystrophin in DMD, a 50 KD subunit of dystrophin associated glycoprotein (DAG) in severe childhood autosomal recessive muscular dystrophy (SCARMD), and subunit M of laminin (merosin) in congenital muscular dystrophy and dy mouse. The vulnerable muscle surface membrane may permit extracellular calcium influx into the sarcoplasm resulting in focal myofibrillar hypercontraction (opaque fiber) and activation of proteases such as calpain and cathepsins. The muscle fiber then undergoes necrosis and allows macrophage invasion, followed by muscle fiber regeneration. Focal myofibrillar degeneration involving rimmed vacuole (RV) formation is an another striking muscle fiber degeneration seen in various neuromuscular diseases including inclusion body myositis (IBM) and distal myopathy with rimmed vacuole formation (DMRV). Abnormal accumulation of ubiquitin, beta-amyloid protein precursor and tau protein has been described in IBM by Askanas et al. The similar findings are also recognizable in DMRV and in an experimentally induced myopathy after long-term chloroquin administration to rat. Therefore, if we clarify the pathomechanism of degenerative process involved in the rimmed vacuole formation, the results may provide some insights into the understanding the process involved in amyloid plaque formation in Alzheimer's disease. PMID- 7774136 TI - [Diagnostic neuropathology supported by immunohistochemistry]. AB - There are various histological components in the central nervous system. When making a neuropathological diagnosis, it is difficult to identify each component. Recently, with the adoption of immunohistochemistry in diagnostic neuropathology, the identification of each component has become relatively easy. Immunohistochemistry is a useful method for staining objective tissues or cells employing the antigen-antibody reaction. Its specificity is very high. In the field of diagnostic neuropathology, immunohistochemical techniques have developed in the diagnosis of brain tumors. With the aid of immunohistochemistry, various findings have been obtained. At the present time, however, the number of available antibodies is rather restricted. As a result, accurate differentiation of microglia and brain macrophage is difficult, and the origin and definition of microglia and brain macrophages are controversial. In the near future, with further progress in immunohistochemical techniques, the number of antibodies will rapidly increase and their sensitivity should improve. When this is achieved, it will be possible to elucidate the pathophysiology of the central nervous system morphologically. PMID- 7774137 TI - Impact on empiric treatment of group A streptococcal pharyngitis using an optical immunoassay. AB - The potential impact of using a rapid diagnostic test (Strep A OIA) on detection and treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in a large-volume pediatric and adolescent clinic was examined. Of 519 swabs processed for both culture and the OIA test, 114 were culture-positive for GABHS compared with 133 positive by the OIA test, for an agreement of 94%. OIA test sensitivity compared with culture was 96%, and specificity was 94%. Forty-seven percent of all study patients were empirically placed on antibiotics. In-clinic OIA testing could have reduced inappropriate therapy and been a cost-effective alternative to culture. PMID- 7774138 TI - Risk of lead poisoning in abused and neglected children. AB - This study examined the prevalence of lead poisoning in 746 abused and neglected children taken into protective custody by Cook County, Illinois, Child Protective Services, Department of Children and Family Services (DCFS). Most of these children had a history of neglect (62%) or dependency (23%); they were predominantly African-American (88%). Venous blood lead concentrations (PbB) were obtained on 589 children, ages 6 months to 6 years, between January 1, 1992, and December 31, 1992. Three hundred eighty-one (64.7%) children tested had a PbB > or = 10 micrograms/dL (0.48 mumol/L); the mean PbB was 12.23 micrograms/dL (0.587 mumol/L). These data support a recommendation for lead screening in any child with a history of abuse or neglect if environmental risk factors cannot be assessed. PMID- 7774139 TI - Identification of sepsis in neonates following maternal antibiotic therapy. AB - To examine the value of current diagnostic tests identifying neonatal sepsis related to intrapartum treatment with antibiotics, we reviewed the charts of 219 mother-infant pairs, of which 139 mothers received intrapartum antibiotics (group 1) and 80 mothers did not (group 2). When compared with group 2 infants, group 1 infants had fewer positive blood cultures (4.3% vs 20%, P < 0.003), blood cultures positive for group B streptococci (GBS) (P < 0.001), and positive urine GBS latex agglutination (LA) tests (P < 0.001). Although the sensitivity of the white blood cell count (WBC) was 81%, the specificity was < 60% in both groups. The specificity of the urine GBS LA test was 92%. These results suggest (1) the WBC will neither confirm nor rule out neonatal septicemia; (2) blood cultures are indicated in suspected neonatal sepsis even if there was maternal intrapartum treatment with antibiotics; and (3) a urine GBS LA test is a useful adjunct in the diagnosis of neonatal GBS septicemia. PMID- 7774140 TI - Failure to clinically predict NICU hearing loss. AB - Neonatal intensive care unit (NICU) survivors demonstrate handicapping sensorineural hearing loss up to 50 times more frequently than normal newborns, yet little is known about the etiology of the hearing loss. Theoretically, accurate identification and triage of a particular infant based on a clinical profile would be useful. Forty NICU graduates of The Massachusetts General Hospital were selected for a detailed retrospective chart review evaluating prenatal, perinatal, and NICU medical conditions and treatment. Twenty-three patients identified with hearing loss and 17 infants with normal hearing were compared clinically. Univariate and multivariate analysis was performed on a subpopulation of patients (20 with hearing loss and 16 with normal hearing). A history of ventilation was associated with hearing loss (P = .0023), but this factor was not absolute. No other clinical parameters were convincingly linked to hearing loss. We conclude that reliance on risk factors is an inadequate clinical method to select a patient for a hearing test and that each NICU survivor deserves audiometric evaluation. PMID- 7774141 TI - Moraxella (Branhamella) catarrhalis bacteremia in children. A report of two patients and review of the literature. AB - We report two cases of Moraxella catarrhalis (M. catarrhalis) bacteremia in apparently healthy children. One patient had bilateral otitis media and the other had pharyngitis and sinusitis; both patients had uncomplicated clinical courses. A literature review revealed 22 reported cases of M. catarrhalis bacteremia in children, 14 (63%) of which occurred in patients who had no identified underlying condition. Eight (36%) cases were seen in children who were immunocompromised. Nine (40%) patients presented with either purpura, petechia, or a maculopapular rash. M. catarrhalis is well known as a respiratory pathogen, but it has not been recognized as a common cause of unsuspected bacteremia in children. PMID- 7774142 TI - A subtle sign of spinal cord lipoma. PMID- 7774143 TI - Esophagitis as a cause of infant colic. PMID- 7774144 TI - Self-induced pneumoparotitis. PMID- 7774145 TI - Reversal of anorexia in a child with partial ornithine transcarbamylase deficiency by cyproheptadine therapy. PMID- 7774146 TI - Congenitally acquired chloroquine-resistant P. falciparum malaria in an infant born in the United States. PMID- 7774147 TI - A common factor for cardiac or respiratory failure in SIDS. PMID- 7774148 TI - Staphylococcus-induced toxic shock following balanitis. PMID- 7774149 TI - Perinatal intracranial hemorrhage due to maternal salicylate ingestion. PMID- 7774150 TI - Is treatment of AOM with once-a-day amoxicillin feasible? PMID- 7774151 TI - Intussusception following ingestion of broken glass. PMID- 7774152 TI - [Health and disease in the 18th century. Communications presented at the meeting of the Swiss Society of the study of the 18th century. Berne, 1-2 October 1993]. PMID- 7774153 TI - [A Swiss medical periodical in the service of enlightenment: Johann Heinrich Rahn's Gazette de Sante]. PMID- 7774154 TI - [Health in Diderot's Encyclopedia]. PMID- 7774155 TI - [Illness as metaphor. New thoughts on an old dispute: Julien Offray de la Mettrie and Albrecht von Haller]. PMID- 7774157 TI - [Dissemination of medical knowledge in Europe during the 18th century]. PMID- 7774156 TI - [National pride and private health]. PMID- 7774158 TI - [Arbitrary limit of the judge in evaluating a crime: forensic medicine in Geneva in the 18th century]. PMID- 7774159 TI - [Isaak Iselin's medical history]. PMID- 7774160 TI - [Johann Kaspar Lavater's physico-theological viewpoint of animal magnetism]. PMID- 7774161 TI - ["Malgre vos defauts je vous aime a la rage". On Johannes von Muller's homoerotic preferences]. PMID- 7774162 TI - [From Ulrich Braker's home pharmacy]. PMID- 7774164 TI - [Death of the king and female disorders: the chief valet of the chamber of Louis XV consults Tissot about his young woman (May 1776)]. PMID- 7774163 TI - ["Every pain is a reminder of our high rank." From the medical record of the young artist Ida Brun]. PMID- 7774165 TI - ["Cette faiblesse originelle de nos nerfs". Intellectuality and the feminine constitution--Julia Bondeli's medical reports]. PMID- 7774166 TI - [Ideals of health]. PMID- 7774167 TI - [Health and illness: tools for satire by Jonathan Swift]. PMID- 7774168 TI - [Medicine and essayistics. Typical poetologic reflections exemplified by the periodical Der Arzt]. PMID- 7774169 TI - ["Der Pobel aber bleibt versaumt"--the calendar as a popular vehicle for public health education]. PMID- 7774170 TI - Individualizing recall intervals in child dental care. AB - Individualizing and extending recall intervals for children have been recommended in Norway to target resources efficiently. Recall intervals were changed for children aged 3-18 years in Drammen from 1991. Clinical time spent by dentists and dental hygienists, dental health status and length of recall intervals were registered from 1990 to 1993. For the child population, the mean recall interval changed from 12.5 to 13.7 months and the annual time spent per child was reduced by 14% from 1990-91 to 1992-93. Adjusted for the decline in number of new decayed teeth, the reduction in time spent was 11%. Children with intervals of 17 to 20 months had fewer new decayed teeth and their care required less personnel time than other children. For children with new decayed teeth, time spent for dental care was not associated with recall interval, while for children without new decayed teeth, longer recall intervals were associated with shorter time for dental care. The variation in number of decayed teeth and time spent for dental care was substantial at all intervals. Individualizing and extending recall intervals to some extent targeted resources at children with more dental disease. However, in the short run, inequality in dental health persisted. Limited extension of recall intervals did not interrupt the long-term trend toward better dental health in the children and substantial resources were saved in the dental services. PMID- 7774171 TI - Dentists' attitudes toward frustrating patient visits: relationship to satisfaction and malpractice complaints. AB - A 22-item questionnaire measuring physician frustration in communicating with patients was adapted to dentists, and its reliability and validity assessed, in a sample of 289 English dental surgeons in general practice in Greater Manchester. Subscales were derived assessing the concepts of unpleasant dentist feelings, lack of communication, patient non-compliance, patient control, and practice organization with Cronbach's alpha ranging from 0.59 to 0.77. Three of five subscale scores (unpleasant feelings, lack of communication, and practice organization) were significantly greater for dentists who had official malpractice complaints to insurers. Similarly, all five subscores were greater for dentists who reported larger numbers of unsatisfactory visits and expressed greater dissatisfaction with dental practice. PMID- 7774172 TI - Effects of lifelong consumption of fluoridated water or use of fluoride supplements on dental caries prevalence. AB - This study was undertaken to determine the prevalence of dental caries in children ages 6-14, from fluoridated and non-fluoridated areas in British Columbia, Canada, and the effects of receiving certain fluoride preventive procedures during childhood. Children from two communities were surveyed using a modified Decayed, Missing and Filled Tooth Surface Index (D1D2MFS). Questionnaires on the use of various fluoride preventive practices and residence histories during childhood were collected. Completed questionnaires were returned and exams were performed on 1131 children. Crude caries prevalence scores for the different fluoride exposure groups were tested for differences in dental age and the level of educational attainment of parents and/or guardians. No significant group differences were found. The 110 children with lifelong exposure only to fluoridated water had 35%, or 0.88 (S.D. = 2.91), fewer decayed or filled tooth surfaces per child (P < 0.07) than children with no reported exposure to systemic fluorides. For the 122 children who had taken fluoride supplements for 4 yr or more, 0.67 fewer decayed and filled tooth surfaces (26% reduction) were observed per child when compared to children with no exposure to fluoridated water or supplements. For children who used fluoride supplements for less than 4 yr, no significant benefits were observed. Approximately 75% of the caries prevalence for control and fluoride-exposed groups was on pit and fissured surfaces. Reductions by surface type showed savings on both smooth and pit and fissured surfaces. PMID- 7774173 TI - Effects of glass ionomer cement, resin-based pit and fissure sealant and HF applications on occlusal caries in a developing country field trial. AB - The aim of this community-oriented study was to evaluate different methods to prevent fissure caries. The following products and measures were tested: 1) glass ionomer cement (GIC) applied by dentist; 2) same material applied by short term (3 days) trained personnel (teachers); 3) application of a 0.5% HF solution three times; 4) an established autopolymerized resin based sealant (Delton). The study was performed in Bangkok, Thailand, a city in a developing country experiencing increasing caries prevalence. Children with at least three sound permanent molars from two age groups, 7-8 and 12-13-yr-olds respectively were chosen from very low to medium socioeconomic level families. 1264 children were systematically assigned to experiment or control groups based on school and DMFT. For the younger age group, the 2 yr mean DFS occlusal increment in the Control group was 0.66 surfaces. Significantly lower increments were observed in the GIC experimental group: 0.17 surfaces applied by the teachers and 0.32 applied by dentist, corresponding to 74% and 52% reductions, respectively. The mean increment in the HF group was 0.44 surfaces, a 33% reduction in relation to the Control group. For the 12-13-yr-olds, the mean occlusal surface DF increment was 0.70 surfaces in the Control group. Almost no occlusal increment was found in the Delton group, 0.05 DFS, a 93% reduction. In the GIC Dentist group, the DFS increment was 0.48 and in the Teacher group 0.56, corresponding to 31% and 20% reduction, respectively. A slight and nonsignificant increase of caries in relation to the Control group was observed in the HF group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774175 TI - Pilot study comparing parents' and third-grade schoolchildren's attitudes toward braces and perceived need for braces. AB - An instrument developed for third-grade schoolchildren and their parents was pilot-tested for its ability to measure orthodontic attitudes and perception of the child's need for braces. Seventy-eight children and 54 parents were surveyed. Forty-six percent of the children wanted braces while 61% believed that they needed braces. Correlation between desire for braces and perceived need was 0.47, suggesting that desire and perceived need were only moderately correlated in children. Sixty-three percent of the parents believed that their child needed braces. Despite such proportions of children and parents perceiving a need for treatment, three-fourths of the children and two-thirds of the parents were satisfied with the appearance of the child's teeth. Attitude subscales, derived from the attitude survey, and clinical orthodontic parameters were used to model children's and parents' perceived need for braces in the child. No clinical parameter was a significant correlate in either children's or parents' model of perceived need. Neither race nor gender contributed significantly to either model. The subscales Concern for Appearance and Social Aspects of Braces were the strongest covariates of children's perceived need for braces. Concern for Appearance was the most important correlate in the parents' model. These data suggest that parents' perceived need for orthodontic treatment for their third grade children is determined primarily by a concern for appearance rather than clinical status. In third-graders, perceived aesthetics and social aspects apparently have more influence than clinical status in creating a perception of need for braces. PMID- 7774174 TI - Evaluation after 4 years of the combined use of fluoride and dental sealants. AB - This study evaluates the caries-preventive potential in permanent teeth of dental sealants when combined with an ongoing, school-based fluoride program. The investigation was designed as a sequential, cross-sectional comparison. Dental caries findings in 1987 for 416 children ages 7-11 and 14-17 who received dental sealants and fluorides were compared with corresponding data derived from 1983 baseline examinations of children who received fluoride therapy only. In addition, sealant retention status was determined. Overall mean DMFS scores in 1987 for children in two age groups combined were 51% lower than in 1983. Also, a surface-specific treatment effect was demonstrated in pit and fissures for both older and younger age groups. The overall proportion of sealants retained on occlusal surfaces of first molars after an average of 2 yr (92%) compared favorably with similar figures cited in the scientific literature. The results of this study suggest that pit and fissure sealants confer additional caries preventive benefits beyond those of fluoride therapy alone. PMID- 7774176 TI - Oral health in Danish hospitalized psychiatric patients. AB - The purpose of the present study was to describe oral health status in a group of hospitalized mental patients, and to study the association between dental caries and mental illness. A total of 278 psychiatric patients admitted to a regional Danish hospital were described with respect to the number of teeth present, DMFS, gingival and periodontal status and presence of removable dentures. The oral health status of the hospitalized mental patients was relatively poor compared with the general population of the area. For instance, actual decayed surfaces were found among 55% of the participants compared to the reference figure of 23% in the general population. A multiple regression analysis demonstrated that DMFS was related to duration of mental illness and to psychiatric diagnosis. Furthermore, a multiple logistic regression analysis revealed that the presence of actual decayed surfaces was associated with neglect of toothbrushing, subjective symptoms of xerostomia and participation in the hospital dental program. To conclude, variables of mental illness and psychiatric treatment and care were demonstrated to influence oral health. This underlines the need of special preventive programs aimed at hospitalized psychiatric patients. PMID- 7774178 TI - Preventive Care Advised (PCA)/Operative Care Advised (OCA)--categorising caries by the management option. AB - Currently a range of systems and classifications are used by clinicians, epidemiologists and clinical research workers to sub-divide carious lesions into different grades. These systems are based on the depth of the lesion and/or the presence/absence of macroscopic cavitation. In order to improve upon the meaningfulness and comparability of such systems in the light of increasing knowledge about the disease process, lesion behaviour and caries management options, the authors propose a new system of categorisation that differentiates between lesions which normally require operative intervention and those which do not. In future, it is proposed that in addition to existing conventional criteria, diagnostic systems should also allow results to be expressed in terms of 1) lesions for which appropriate non-invasive Preventive Care Is Advised (PCA lesions) and 2) lesions for which Operative Care Is Advised (OCA lesions). Locally acceptable sub-divisions may have to be developed and agreed for certain specific applications. The adoption of this additional nomenclature and approach in the future should aid communications between the different groups involved in caries diagnosis and research. It may facilitate the dissemination of research findings, as well as helping to "drive" researchers working on caries diagnostic methods to focus on techniques which will aid in the accurate assessment of lesion activity and behaviour. Such a focus should also increase our understanding of treatment decision making and promote the development of clinical guidelines. The facility to retain existing criteria in parallel, for local and other purposes, would preserve comparability with data collected previously. PMID- 7774177 TI - Prevalence study of oral mucosal lesions in a selected Cambodian population. AB - The aim of this study was to investigate the epidemiology of oral mucosal lesions in a selected Cambodian population to obtain pilot data useful in planning an oral health data base for the country. Due to unstable conditions in Cambodia, the validity of population data related to present census information is highly questionable. Therefore, prior to this investigation a census registration was carried out using local health workers as registrars in nine villages of a commune. In the period July 4-31, 1991, a total of 1319 individuals (953 women, 366 men, 15-99 yr) were examined by one oral surgeon in the nine villages of Kok Trop Commune, Kandal Stung District, southwest of the capital Phnom Penh. Clinical diagnoses were based on WHO criteria. Information on smoking habits, betel nut chewing habits, and alcohol use was collected by 4 Khmer dental personnel. In total, 71 lesions were recorded in 64 (4.9%) individuals. Leukoplakia was found in 1.1%, lichen lesions in 1.8%, candidosis in 1.4%, submucous fibrosis in 0.2%, cancer in 0.1% and other diagnoses in 0.8%. The prevalence of leukoplakia was 2.2% and 0.6% among men and women respectively, a statistically significant difference (P < 0.05). There were significantly more smokers (P < 0.01) among subjects with leukoplakia (64.3%) than among those without this lesion (28.6%). All subjects with lichen lesions were women. The age adjusted relative risk for developing lichen among betel nut chewers as compared to non-chewers was 3.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774179 TI - Caries experience in urban and rural Chilean 3-year-olds. PMID- 7774180 TI - Need for orthodontic treatment in Northern Ireland. PMID- 7774181 TI - Recall intervals, dental hygienists and quality in child dental care. AB - Decline in dental disease and the need to provide dental care efficiently suggest changes in clinical and administrative routines in public dental care provision for children. A field project in Norway demonstrated productivity gains after the introduction of individualized recall intervals and using dental hygienists to conduct recall examinations. The purpose of the present study was to assess changes in the quality of dental health outcome and changes in the quality of the process of dental care provision. Recall intervals were increased from a target of 12 months to 16 and 18 months in two districts. Dental hygienists undertook all recall examinations and referred to dentists those patients who required operative care. Bitewing radiographs were inspected for all 18-yr-olds who were examined in 1989, 1990 and 1991 (n = 956) and for those who were examined before the changes were implemented in 1987 (n = 300). For each child, approximal caries on 24 surfaces was scored according to a 4-point severity scale. Clinical records were examined to determine what treatment had been provided. For each year after the changes were implemented, the quality of health outcome was assessed by comparing the radiographic caries prevalence and the number of sound surfaces with 1987 data. Quality in the process of care provision was indicated by the treatment decisions for approximal caries and by the proportion of uninterpretable surfaces on radiographs for each study year. The mean number of sound surfaces increased over time. A declining proportion of sound surfaces was restored over the study period, and almost all caries lesions extending deep into dentine were restored. Radiographic quality improved during the project period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774182 TI - A critical commentary and updating of the guinea pig maximization test. AB - The guinea pig maximization test (GPMT) of Magnusson and Kligman was published in 1969. Since then, a vast body of practical experience with the test has been accumulated. New information requires that certain aspects of the procedure be re evaluated, especially with regard to the interpretation of challenge results. In particular, awareness of the phenomenon of hyperirritable skin (the 'angry back' phenomenon) suggests that presently used controls are not always adequate and may overstate allergenicity owing to false-positive reactions. The control group should be exposed to a chemical insult at induction which provokes an inflammatory reaction comparable to the test substance. We present strategies to distinguish irritant from allergic responses. Allergic reactions should persist on rechallenge weeks later, while nonspecific irritant reactions generally fade and are irreproducible in particular animals. Finally, when a chemical is identified as a contact sensitizer in the GPMT, that result is simply a categorical statement of a theoretical hazard. An assessment of risk is necessary to estimate the relevance of the test result to usage in the real world. PMID- 7774183 TI - Patch test results with serial dilutions of nickel sulfate (with and without detergent), palladium chloride, and nickel and palladium metal plates. AB - Clinical experience suggests the existence of different degrees of sensitivity in nickel-allergic patients. For quantification of this phenomenon, 462 consecutive patients with previously diagnosed or strongly suspected nickel allergy were tested with serial dilution patch tests with 5 ppm to 5% nickel sulfate in pet. (Ni), and 5 ppm to 1% nickel sulfate in pet. with 1% detergent (Ni/D). Additionally, nickel and palladium metal plates were tested in 103, and cobalt salts, dichromate and palladium chloride (PdCl2) in most patients. 332 patients reacted positively to Ni or Ni/D. The influence of a concomitantly administered detergent was not significant. A significant correlation was found between positive reactions to low concentrations of Ni (or Ni/D), i.e., 0.1% or less (N = 166), and concomitant reactions to nickel metal plates, cobalt salts and PdCl2 and a history of ear piercing with metal intolerance. The clinical relevance of reactions to PdCl2 is at present not clear. A subgroup of nickel-allergic patients with "high sensitivity" can be defined. In future studies further addressing the clinical relevance of high versus low sensitivity, patch testing with 0.01, 0.1, 1.0 and 5% nickel sulfate in pet. is recommended instead of routine tests with 5% only. PMID- 7774184 TI - Contact allergy to gold sodium thiosulfate. AB - 278 consecutive patients with suspected contact dermatitis were patch tested with the European standard series and gold sodium thiosulfate (0.5% pet.): 13 patients (4.6%) had a positive allergic response to gold sodium thiosulfate (GST). All of these patients were female, with a mean age of 37 years. The most frequent site of eczema in these patients was the head and neck (62%). A seborrhoeic distribution of eczema was common. 46% had involvement of the limbs, 15% had a perianal or perivulval rash. The mean duration of eczema in this group of patients was 15.8 months. 54% of patients allergic to gold were also allergic to nickel. Biopsy of positive patch test reactions to GST were consistent with allergic contact dermatitis. PMID- 7774185 TI - Ear piercing, and nickel and cobalt sensitization, in 520 young Swedish men doing compulsory military service. AB - Piercing the earlobes has increased in popularity among males in recent years. This habit would be expected to increase the incidence of nickel and cobalt sensitization. Patch testing with nickel sulfate and cobalt chloride was performed in 520 young Swedish men doing compulsory military service. The overall frequency of nickel/cobalt positive tests was 4.2%. The prevalence of nickel/cobalt positive tests was significantly higher (p < 0.05) in 152 men with pierced earlobes (7.9%) than in those 368 with unpierced earlobes (2.7%). A history of hand eczema (7/152 = 4.6%) or other types of eczema (22/152 = 14.5%) in individuals with pierced earlobes was no more common than in those with unpierced earlobes: 24/368 = 6.5% and 51/386 = 13.9%, respectively (n.s.). Hand eczema was no more common in sensitized (1/22 = 4.5%) than in nonsensitized individuals (32/498 = 6.4%) (n.s.). PMID- 7774186 TI - Hand eczema in Finnish farmers. A questionnaire-based clinical study. AB - In a population of 2005 Finnish farmers, 172 (8.6%) reported hand or forearm dermatoses in a self-administered questionnaire. 138 (80%) of them attended a clinical examination. Skin prick tests (SPTs) were done to 80% and patch tests (PTs) to 77% of the examined farmers. 93% of hand dermatoses were eczema and 70% were considered work-related. Cow allergy was found in 41 of 104 prick- and patch tested farmers (39%). Immediate allergy to cow epithelium was encountered in a total of 28/41, in 20 with SPTs, and in 8 only with 20 min PTs. Delayed contact allergy to cow dander was found in 27/41. The result suggests that in addition to SPTs using commercial cow epithelium extract, PTs using fresh cow dander should also be done, and both immediate and delayed responses should be read. PMID- 7774188 TI - Allergic contact dermatitis from the newly introduced fungicide fluazinam. AB - In spring 1992, several farmers in the western part of The Netherlands developed dermatitis on their hands, forearms and face. In some, the legs, trunk and genitals were also affected. Complaints ranged from a mildly itchy, papular rash to a painful, weeping and blistering dermatitis. Medical aid was needed by 5/9 of them. Some of the farmers grew seed potatoes, the others cultivated lilies. All of them had in common that their complaints emerged after repeated application of a new fungicide over several weeks. The fungicide was Shirlan, with fluazinam as its active ingredient. 9 farmers were patch tested with a concentration range of the whole formulation (aq.) and of the active ingredient (pet.). In 7 of 9 farmers, positive patch tests were scored with both the whole formulation (down to 0.01% aq.) and fluazinam itself (down to 0.1% pet.). Patch tests in consecutive control patients (n = 10) were all negative. As it was impossible to substitute fluazinam as the active ingredient, farmers are now supplied with detailed information as to how to avoid skin contact as much as feasible. PMID- 7774187 TI - Occupational allergic contact dermatitis from ethyl cyanoacrylate. AB - Glues based on cyanoacrylates are widely used as contact adhesives for metal, glass, rubber, plastics and textiles, as well for biological materials, including binding tissues and sealing wounds in surgery. In this paper, an apprentice cobbler with an occupational allergic contact dermatitis from an ethyl cyanoacrylate glue, in which the major monomer was shown to be the sensitizer, is reported. Initial patch testing with the cyanoacrylate glue dissolved in acetone with the Finn Chamber (aluminium) technique yielded false-negative reactions. Positive test reactions were obtained with the same preparations using Van der Bend chambers. With petrolatum as vehicle for the glue, there was no difference between Finn Chamber technique and Van der Bend chamber technique. The role of aluminium in the false-negative reactions is discussed. PMID- 7774189 TI - Irritant effects of a detergent in wash and chamber tests. AB - Irritant properties of detergents can be tested by using patch and chamber tests and various kinds of use tests. The aim of the present study was to compare the results of use and 12 mm Finn Chamber tests. Study subjects (10 atopic and 11 non atopic medical students) washed the outer aspect of 1 upper arm with liquid detergent for 1 minute 2 x daily for 1 week. 48-h chamber test with 5 concentrations of the same detergent in water were concurrently applied to upper back skin. Transepidermal water loss (TEWL), electrical capacitance and skin blood flow were measured to quantify reactions on days 0, 2, 5 and 7. Irritant contact dermatitis developed equally in atopics and non-atopics in the wash test, whereas in the chamber test with a 10% aq. solution of the detergent, increase in TEWL was significantly higher in atopics than in non-atopics. The chamber test results thus predicted poorly the result of the wash test. This might indicate that the wash test and the chamber test measure different aspects of skin barrier function. PMID- 7774190 TI - The influence of patch tests with clobetasol propionate on adjacent patch test reactions. AB - Contact allergy to corticosteroids now seems frequent among patients being patch tested. As corticosteroids are intrinsically anti-inflammatory, we investigated whether patch tests with a potent corticosteroid might suppress simultaneous adjacent patch test reactions to another allergen. Nickel-sensitive subjects were patch tested with an aqueous dilution series of nickel in duplicate, adjacent to patch tests with clobetasol propionate 1% in ethanol and with ethanol, respectively. Statistical evaluation of the results obtained in 2 different centers, using their own patch test techniques, did not reveal any suppression of the positive nickel patch test reactions. PMID- 7774191 TI - Occupational sensitivity to rubber. PMID- 7774192 TI - Allergic contact dermatitis from tolnaftate. PMID- 7774193 TI - Contact urticaria from cucumber pickle and strawberry. PMID- 7774194 TI - Allergic contact dermatitis from epsilon-caprolactam. PMID- 7774195 TI - Contact sensitivity to cyanoacrylate nail-adhesive with dermatitis at remote sites. PMID- 7774197 TI - Latex allergy among hairdressers. PMID- 7774196 TI - Photoallergy to oxybenzone in cosmetic creams. PMID- 7774198 TI - Allergic contact dermatitis from a wart remover solution. PMID- 7774199 TI - An unusual complication of patch testing. PMID- 7774200 TI - Allergy to epoxy compounds over a decade. PMID- 7774201 TI - Allergic contact dermatitis due to piketoprofen. PMID- 7774202 TI - In vitro release of interferon-gamma by peripheral blood mononuclear cells of a patient with carbamazepine-induced allergic drug eruption in response to stimulation with carbamazepine. PMID- 7774203 TI - Allergic contact dermatitis from Rhus toxicodendron in a phytotherapeutic preparation. PMID- 7774204 TI - Contact dermatitis from tantalum. PMID- 7774205 TI - Environmental glass fibre counts and skin symptoms. PMID- 7774206 TI - Colophony in bindi adhesive. PMID- 7774207 TI - Allergic contact conjunctivitis and blepharitis from tobramycin. PMID- 7774208 TI - Contact dermatitis from clotrimazole. PMID- 7774209 TI - A simple method of determining TS-F-R in nail polish. PMID- 7774210 TI - Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. AB - OBJECTIVES: This report examines the frequency, type, and prognostic factors of medical (nonneurologic) complications after subarachnoid hemorrhage in a large, prospective study. The influences of contemporary neurosurgical, neurological, and critical care practice on mortality and morbidity rates after aneurysmal subarachnoid hemorrhage are evaluated. DESIGN: A study of medical complications observed in the placebo limb of a large, randomized, controlled trial of the calcium antagonist, nicardipine, after subarachnoid hemorrhage. SETTING: Patients were recruited from 50 hospitals in 41 neurosurgical centers in the United States and Canada. PATIENTS: A total of 457 patients with subarachnoid hemorrhage, > or = 18 yrs of age, were randomly assigned to the placebo group. All patients arrived at the participating center within 7 days (mean 1.0 +/- 1.8 [SD] days) of rupture of an angiographically documented saccular aneurysm. MEASUREMENTS AND MAIN RESULTS: The frequency rates of symptomatic vasospasm, rebleeding, and total mortality rate after subarachnoid hemorrhage at 3-month follow-up were 46%, 7%, and 19%, respectively. The frequency of having at least one severe (life threatening) medical complication was 40%. The proportion of deaths from medical complications was 23%. This value was comparable with the proportion of deaths attributed to the direct effects of the initial hemorrhage (19%), rebleeding (22%), and vasospasm (23%) after aneurysmal rupture. The frequency of life threatening cardiac arrhythmias was 5%; less ominous rhythm disturbances occurred in 30% of the patients. There was an increased frequency of cardiac arrhythmias on the day of, or day after, aneurysm surgery. Pulmonary edema occurred in 23% of the patients, with a 6% occurrence rate incidence of severe pulmonary edema. There was a wide variation from center to center, with the greatest frequency on days 3 through 7. There was a nonsignificant association of pulmonary edema with the use of hypertensive hypervolemic therapy (p = .10), and a significant association with the timing of surgery (p < .05). Some degree of hepatic dysfunction was noted in 24% of patients, the majority with only mild abnormalities of hepatic enzymes with no clinical accompaniment (4% frequency of severe hepatic dysfunction). Thrombocytopenia occurred in 4% of patients, usually in the setting of sepsis. Renal dysfunction was reported in 7% of the patients, with 15% of that figure deemed to be of life-threatening severity. There was an association (p = .001) with antibiotic therapy. CONCLUSIONS: Potentially preventable medical complications after ruptured cerebral aneurysm add to the total mortality rate of patients, and may increase length of hospital stay in the critical care setting. The proportion of deaths after subarachnoid hemorrhage from medical complications equals those deaths from either direct effects, rebleeding, or vasospasm individually. Pulmonary complications are the most common nonneurologic cause of death. Cardiac arrhythmia, although frequent, was not associated with significant mortality. The frequency of cardiac arrhythmia and pulmonary edema increased on the day of, or day after, aneurysm surgery. Renal and hepatic dysfunction, and blood dyscrasias, were also observed, underscoring the need for meticulous monitoring for metabolic and hematologic derangements. PMID- 7774211 TI - NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, reverses interleukin 2-induced hypotension. AB - OBJECTIVE: To evaluate the role of NG-methyl-L-arginine as a modulator of the hyperdynamic shock induced by the administration of interleukin-2 (IL-2). DESIGN: A prospective, pilot clinical study. SETTING: Intensive care unit of a tertiary care center. PATIENTS: Three sequential patients with metastatic renal cell carcinoma who developed hypotension during their first course of treatment with high-dose IL-2 (18 x 10(6) IU/m2/day by continuous infusion for 5 days). INTERVENTIONS: Upon developing hypotension during their subsequent therapy with IL-2, patients were administered 12 mg/kg of NG-methyl-L-arginine. Thereafter, a dose of 4 mg/kg was given every 4 hrs, as needed, to maintain the systolic blood pressure above 100 mm Hg. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamic monitoring was instituted before the initiation of treatment with IL-2. Differences noted before, and 15 mins after, the administration of NG-methyl-L arginine were analyzed using the paired t-test. NG-methyl-L-arginine (12 mg/kg) induced a significant antihypotensive effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm Hg), accompanied by an increase of the systemic vascular resistance (549 +/- 51 to 860 +/- 167 dyne.sec/cm5) and pulmonary vascular resistance (81 +/- 16 to 117 +/- 29 dyne.sec/cm5). A decrease in the cardiac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m2). No significant changes in pulmonary artery occlusion and central venous pressures were observed. Maintenance doses of 4 mg/kg of NG-methyl-L-arginine induced similar hemodynamic results, although the duration of the antihypotensive effect of NG-methyl-L arginine decreased with sequential doses. CONCLUSIONS: The hemodynamic effects induced by IL-2 administration are reversed by NG-methyl-L-arginine, a nitric oxide synthesis inhibitor. These results provide evidence for the biological activity of NG-methyl-L-arginine when administered alone to hypotensive patients. While no adverse effects were observed in this preliminary study, issues of toxicity and effectiveness need to be defined further in formal clinical trials. NG-methyl-L-arginine may play a therapeutic role in the modulation of the extreme vasodilation induced by cytokine administration or in septic shock. PMID- 7774212 TI - Frequency of mortality and myocardial infarction during maximizing oxygen delivery: a prospective, randomized trial. AB - OBJECTIVES: To determine the frequency of myocardial infarction and mortality during treatment that increased oxygen delivery (DO2) to > or = 600 mL/min/m2. To define the characteristics of patients achieving a high DO2 without inotropes in order to guide future studies. DESIGN: A prospective, randomized, controlled trial. SETTING: Two surgical intensive care units at The Queen's Medical Center in the University of Hawaii Surgical Residency Program. PATIENTS: Eighty-nine surgical patients (> or = 18 yrs of age), who were admitted to a surgical intensive care unit and who required pulmonary artery catheter monitoring, were selected for the study. Diagnoses included sepsis, septic shock, adult respiratory distress syndrome, or hypovolemic shock. Patients facing imminent death were excluded from the study. INTERVENTIONS: The treatment group received fluid boluses, blood products, and inotropes, as needed, to achieve a DO2 of > or = 600 mL/min/m2 in the first 24 hrs. Using the same interventions, we treated the control group to reach a DO2 of 450 to 550 mL/min/m2. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were obtained every 4 hrs until the pulmonary artery catheter was removed. DO2 and oxygen consumption were calculated by standard formulas. Serial creatine kinase myocardial fraction and electrocardiograms were documented for the first 48 hrs after study entry and for any new onset of arrhythmia or increasing hemodynamic instability. The patients who generated a high DO2 (> or = 600 mL/min/m2) with only preload treatment were reflective of patients with better cardiac reserve and low mortality rates. These patients, from both treatment and control groups, were excluded in the final analysis. The treatment group who received inotropes to achieve the high DO2 had a 14% mortality rate. Those patients who failed to achieve the high DO2 had a 67% mortality rate, and the control group who achieved a normal DO2 had a 62% mortality rate (p = .005). The frequency of myocardial infarction after study entry was 5.6% (five of 89 patients). This rate was not higher among the groups who received inotropes. Logistic regression analysis showed that age of > or = 50 yrs could be used to classify patients as not self-generating, with an 83% chance of being correct. CONCLUSIONS: The group that required catecholamines to achieve a DO2 of > or = 600 mL/min/m2 had a lower mortality rate, with no increase in the frequency of myocardial infarction. Future prospective, controlled trials examining select groups of patients (age > or = 50 yrs) may demonstrate a difference between control and treatment groups by eliminating the majority of patients who generate the high DO2 with only preload augmentation. PMID- 7774213 TI - Effect of the antiendotoxic agent, taurolidine, in the treatment of sepsis syndrome: a placebo-controlled, double-blind trial. AB - OBJECTIVE: To assess the benefit gained from administration of the antiendotoxic drug, taurolidine, on outcome in critically ill patients with sepsis syndrome. DESIGN: A prospective, randomized, double-blind trial. SETTING: The general intensive therapy unit in a university teaching hospital. PATIENTS: One hundred patients admitted with sepsis syndrome over a 2-yr period. INTERVENTIONS: Patients were randomized to receive the amino-acid derivative, taurolidine, or an identically presented placebo. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation II (APACHE II), sepsis, and organ failure scores were measured daily. Blood for culture and endotoxin assay (using the limulus amoebocyte lysate assay) was sampled every 12 hrs for up to 5 days. Hemodynamic variables were recorded every 4 hrs. Forty-nine patients received taurolidine and 51 patients received placebo. There was no difference in APACHE II score, Sepsis Score, or presence of infections between the groups. The frequency of Gram negative bacteremia was low at 12%. There was no difference in endotoxin activity, clinical or bacteriologic outcome, resolution of organ failure, or mortality rate between groups. Predicted risk of death for patients receiving taurolidine was 45%, and the actual mortality rate was 44%. In the group that received placebo, the predicted mortality rate was 38% and the actual mortality rate was 39%. CONCLUSION: Taurolidine had no beneficial therapeutic effect on the outcome of patients admitted to the intensive therapy unit with sepsis syndrome, using clinical, bacteriologic outcomes, progression of endotoxemia, resolution of organ failure, and 28-day mortality rate as end points. PMID- 7774214 TI - Long-term survival after intensive care unit admission with sepsis. AB - OBJECTIVE: To evaluate the long-term survival of critically ill patients with sepsis and to assess the factors predictive of long-term survival (> 1 month after admission date). DESIGN: Prospective, cohort study. SETTING: Medical/surgical intensive care unit (ICU) in a multidisciplinary community hospital. PATIENTS: All patients admitted to the ICU from January 1, 1987 to March 31, 1991 who both demonstrated clinical evidence of the systemic inflammatory response syndrome and yielded blood cultures positive for a bacterium or fungus (n = 153). INTERVENTIONS: Random set of procedures normally performed in an ICU setting. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, including age, blood culture results, comorbid conditions, and severity of illness as estimated by the Acute Physiology Score of the Acute Physiology and Chronic Health Evaluation II prognostic system were recorded. Follow-up evaluation utilizing the National Death Index provided survival outcome for all patients 1 yr after hospital discharge. The mortality rate at hospital discharge was 51.0%, and mortality rates at 1 month, 6 months, and 1 yr after admission date were 40.5%, 64.7%, and 71.9%, respectively. A total of 33 patients survived beyond the period of observation. The analyses demonstrated the following findings: a) the survival rate was negatively correlated with the Acute Physiology Score up to 1 month after hospital admission date, but uncorrelated thereafter; b) fungal infections, such as Candida, had the shortest survival prospects of any blood-borne infection; and c) both malignancy and human immunodeficiency virus infection contributed to poorer outcomes, but differed in their patterns of long-term survival. CONCLUSIONS: The most critical period for surveillance of bacteremic patients was in months 2 through 6 after discharge, during which time, the percentage of patients surviving decreased dramatically. The degree of physiologic derangement, as measured by the Acute Physiology Score, was a useful measure of prognosis within the first month after the score was assessed at ICU admission. However, beyond this period, prognostic utility decreased significantly. Healthcare providers should use caution concerning the expected survival of hospitalized patients with human immunodeficiency virus, based on experience with distinct conditions, such as malignancies. PMID- 7774215 TI - Triage considerations for patients with acute gastrointestinal hemorrhage admitted to a medical intensive care unit. AB - OBJECTIVE: To determine whether previously identified clinical criteria, available at the time of triage, can predict clinical outcomes for patients with acute gastrointestinal (GI) hemorrhage. DESIGN: An inception cohort study. SETTING: Barnes Hospital, an academic tertiary care center. PATIENTS: One hundred eight consecutive hospital admissions (103 patients) triaged to intensive care for GI hemorrhage. INTERVENTIONS: Prospective patient surveillance, data collection, and risk stratification using preselected clinical criteria and outcomes assessment. MEASUREMENTS AND MAIN RESULTS: Using clinical data available at the time of triage, 28 (25.9%) intensive care unit admissions were classified as low risk for having poor outcomes. There was no difference in the distribution of upper and lower GI tract sources of hemorrhage for the two risk groups (p = .310). Stigmata of recent hemorrhage were endoscopically identified for six (21.4%) of the low-risk patient admissions and for 16 (20.0%) of the high-risk patient admissions (p = .872). Patient admissions identified as low risk had significantly lower rates of recurrent GI hemorrhage (3.6% vs. 22.5%; p = .022), less acquired organ system derangements (1.0 +/- 0.3 vs. 1.5 +/- 1.0 organs; p < .001), shorter lengths of hospitalization (4.9 +/- 3.5 vs. 8.8 +/- 7.4 days; p < .001), required transfusion with fewer units of packed red blood cells (1.3 +/- 1.2 vs. 6.2 +/- 4.7 units; p < .001), and had a lower overall hospital mortality rate (0.0% vs. 21.3%; p = .008) compared with patient admissions identified as being high risk. CONCLUSION: These data suggest that objective clinical criteria, available at the time of triage determination, can be utilized to identify a low risk group of patients with acute GI hemorrhage, having favorable outcomes and potentially no need for intensive care unit services. PMID- 7774216 TI - Enteral nutrition in the critically ill patient: a prospective survey. AB - OBJECTIVES: To describe current enteral nutrition-prescribing practices for critically ill patients, and to identify factors associated with initiation of, and tolerance to, enteral nutrition. DESIGN: A prospective, cohort study. SETTING: Two tertiary care medical-surgical intensive care units (ICU) in Ontario, Canada. PATIENTS: We enrolled 99 consecutive patients who were expected to stay in the ICU for > 3 days and who were unable to tolerate oral nutrition. We followed patients for 21 days or until they tolerated enteral nutrition, tolerated oral nutrition, were discharged from the ICU, or died. MEASUREMENTS AND MAIN RESULTS: We recorded time elapsed from ICU admission to initiation and tolerance of enteral feedings, and examined factors associated with these events. We defined tolerance as receiving 90% of estimated daily energy requirements for > 48 hrs without gastrointestinal dysfunction (i.e., high gastric residuals, vomiting, diarrhea, abdominal distention). Seventy-three (74%) of 99 patients were started on enteral feedings an average 3.1 days (range 1 to 18) after ICU admission. Of 26 patients never started on enteral nutrition, three (12.5%) patients eventually tolerated oral nutrition, 14 (54.0%) patients were discharged from the ICU, and seven (27.0%) patients died. Reasons for not initiating enteral nutrition included absence of bowel sounds (27.0%), high nasogastric drainage (16.9%), contraindication to enteral nutrition (16.7%), tolerance of oral nutrition (6.8%), and no apparent reason (5.1%). Abdominal surgery, use of vasoactive drugs, and admission to one hospital made initiation of enteral nutrition less likely, whereas presence of bowel sounds and admission to the other hospital made initiation of enteral nutrition more likely. Thirty-five (42.9%) of 73 patients started on enteral nutrition achieved tolerance of the regimen. The average time from ICU admission to tolerance of feedings was 5.8 days (range 1 to 14). Once started on enteral nutrition, the most common reasons for decreasing or discontinuing feedings included high gastric residuals (51.0%), mechanical feeding tube problems (15.4%), medical or surgical procedures (5.4%), and vomiting (5.1%). Use of paralytic agents and the presence of high gastric residuals were associated with intolerance. Of 38 patients who did not achieve tolerance, 20 (52.6%) patients were discharged from the ICU, eight (21.0%) patients died, and eight (21.0%) patients eventually tolerated oral nutrition. CONCLUSIONS: Enteral nutrition is not started in all eligible ICU patients. Approximately half of those patients receiving enteral nutrition achieved tolerance of the regimen. Gastrointestinal dysfunction causing intolerance to enteral nutrition is a common reason for not starting, or discontinuing, feedings. PMID- 7774218 TI - Effect of computerized charting on nursing activity in intensive care. AB - OBJECTIVE: To measure the impact on nursing activity of introducing computerized medical records into intensive care units (ICUs). DESIGN: Prospective data collection monitoring the activity of ICU nurses before and after installation of a computerized charting system. SETTING: A six-bed coronary care unit and an eight-bed medical ICU at the Minneapolis VA Medical Center. SUBJECTS: Registered nurses providing intensive care services. INTERVENTIONS: Installation of a Clinical Information System that computerized the ICU medical records. MEASUREMENTS AND MAIN RESULTS: Before computer installation, nurses spent 24% of their time manipulating data (7% gathering and 17% charting). After installation, charting time decreased to 10%, and data gathering time decreased to 4%, while 10% of time was spent at computer terminals entering or reviewing data. The total time manipulating data post-installation was thus 24% (i.e., unchanged from previous). Computerized charting did not alter time spent in patients' rooms (43% pre- and 43% postinstallation) compared with time spent at the central station (37% pre- and 36% post-installation) or elsewhere (20% pre- and 21% postinstallation). Relative time spent at various tasks varied between units and from shift to shift, but the net effect of computerized charting was that nurses had more time available at the central station for monitoring, and that the computer terminals were used primarily in the patient rooms. CONCLUSIONS: Computerized charting will not necessarily provide ICU nurses with a net excess of time for tasks unrelated to manipulating data. PMID- 7774217 TI - Chemical compatibility of inotropic and vasoactive agents delivered via a multiple line infusion system. AB - OBJECTIVES: To determine the chemical compatibility of three different triple drug admixtures diluted with either 5% dextrose in water or 0.9% NaCl solution when administered via a multiple line infusion system (Omni-Flow 4000, Abbott Laboratories, Abbott Park, IL). The triple drug admixtures were: a) dobutamine, dopamine, and norepinephrine; b) nitroglycerin, sodium nitroprusside, and dobutamine; and c) nitroglycerin, dopamine, and dobutamine. DESIGN: Two phase in vitro compatibility study. SETTING: Pharmaceutical laboratory. SUBJECTS: None. INTERVENTIONS: Phase I assessed chemical stability when the triple drug admixture was placed in a single container. In phase II, individual drug components of the admixtures were infused via the multiple line infusion system. Samples were collected at time 0, 1 hr, 2 hrs, 4 hrs, 12 hrs, and 24 hrs. All samples were frozen and stored at -70 degrees C until assayed. MEASUREMENTS AND MAIN RESULTS: Samples were assayed using stability-indicating high performance liquid chromatography. The triple drug admixtures were considered to be chemically stable if there was < or = 10% loss of stated potency over 24 hrs. In phase I, chemical stability was observed for all triple drug admixtures at 24 hrs. In phase II, dobutamine, dopamine, norepinephrine, and sodium nitroprusside showed chemical stability at 24 hrs. Nitroglycerin showed a two-fold increase in concentration at 24 hrs compared with the initial concentration through the test infusion system; however, this amount was still one third lower than originally anticipated. CONCLUSIONS: All triple drug admixtures were chemically stable when placed in single containers. Dobutamine, norepinephrine, and sodium nitroprusside showed chemical stability when delivered via a multiple line infusion system. The reduced recovery of nitroglycerin from the test infusion system may result from adsorption of the nitroglycerin to the polyvinyl chloride plastic cassette and tubing during infusion. PMID- 7774219 TI - Variability of intrinsic positive end-expiratory pressure in patients receiving mechanical ventilation. AB - OBJECTIVE: Since variations in breathing pattern may affect the level of intrinsic positive end-expiratory pressure (PEEP), breath-to-breath variation of intrinsic PEEP was assessed. DESIGN: Descriptive and prospective study. SETTING: Medical intensive care unit of a university teaching hospital. PATIENTS: Thirty four patients requiring mechanical ventilation for a period of time due to respiratory failure. MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was determined using simultaneous recordings of the esophageal pressure and airflow. The breath to-breath intrinsic PEEP, respiratory rate, tidal volume, inspiratory time, and fractional inspiratory time were measured. Intrinsic PEEP was noted in 33 of 34 patients. For all patients, the mean intrinsic PEEP was 3.59 cm H2O. The group mean standard deviation (SD) of the intrinsic PEEP over 35 breaths was 2.68 cm H2O. In 17 chronic obstructive pulmonary disease patients, the mean intrinsic PEEP was 4.69 cm H2O and the group mean SD of the intrinsic PEEP was 3.19 cm H2O. In the subgroup of patients with significant intrinsic PEEP, the mean intrinsic PEEP was 6.69 cm H2O and the group mean SD was 4.29 cm H2O. The group mean coefficient of variation of intrinsic PEEP for all 34 patients was 123%. Among the 15 patients with clinically significant intrinsic PEEP, the coefficient of variation was smaller (74%). We did not find significant correlation between the coefficients of variation of breathing pattern parameters and the coefficients of variation of intrinsic PEEP. CONCLUSIONS: We conclude that the occurrence rate of intrinsic PEEP in mechanically ventilated patients is high. The degree of variability in intrinsic PEEP on a breath-to-breath basis is also high. It may be difficult to find a specific level of intrinsic PEEP. Addition of external positive end-expiratory pressure without considering the breath-to-breath variability may lead to overdistention of the lung. PMID- 7774220 TI - Glycosylated recombinant human tumor necrosis factor binding protein-1 reduces mortality, shock, and production of tumor necrosis factor in rabbit Escherichia coli sepsis. AB - OBJECTIVE: To examine the effect of glycosylated recombinant human tumor necrosis factor binding protein-1 (r-hTNF binding protein-1), the extracellular domain of the tumor necrosis factor receptor p55 produced in mammalian cells, in a rabbit model of circulatory shock due to Escherichia coli. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital research laboratory. SUBJECTS: Eighteen female, New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits, infused with E. coli (10(9) organisms/kg), were pretreated with either r hTNF binding protein-1 or saline. Mean arterial pressure, central venous pressure, cardiac output, and heart rate were recorded every 20 mins for 1 hr before, and for 4 hrs after, the infusion of E. coli. Blood samples were obtained at 1-hr intervals for platelet count and white blood cell count, r-hTNF binding protein-1, and tumor necrosis factor (TNF) measurements. MEASUREMENTS AND MAIN RESULTS: Administration of r-hTNF binding protein-1 resulted in improvement of mean arterial pressure, cardiac output, and systemic vascular resistance, as compared with the vehicle-treated group (p < .05). Treatment with r-hTNF binding protein-1 was associated with 100% survival, as compared with 55.6% of the saline treated rabbits (p < .05). Approximately 85% of r-hTNF binding protein-1 was cleared from the circulation 1 hr after the bolus injection (from 171 +/- 27 micrograms/mL at time = 0, to 27 +/- 4 micrograms/mL at 60 mins, decreasing to 6 +/- 2 micrograms/mL for the next 3 hrs). The r-hTNF binding protein-1-treated rabbits had lower serum TNF bioactivity during the first 2 hrs (p < .01). The decreased bioactivity of TNF was confirmed by a specific radioimmunoassay for rabbit TNF. However, at 4 hrs, the vehicle-treated rabbits had lower serum bioactive TNF concentrations (p < .05). The decrease in TNF concentrations in the r-hTNF binding protein-1-treated rabbits resulted from decreased production and, in part, from carry-over of r-hTNF binding protein-1 into the bioassay. CONCLUSIONS: Treatment with r-hTNF binding protein-1 improved hemodynamic variables and survival of E. coli-challenged rabbits. Administration of r-hTNF binding protein-1 suppressed bioactivity of TNF in the circulation of these rabbits, and the production of TNF as well. PMID- 7774221 TI - Increasing organ blood flow during cardiopulmonary bypass in pigs: comparison of dopamine and perfusion pressure. AB - OBJECTIVE: To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN: Randomized crossover trial. SETTING: Animal research laboratory in a university medical center. SUBJECTS: Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION: Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS: Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS: These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass. PMID- 7774222 TI - Interleukin-1 receptor antagonist attenuates leukocyte-endothelial interactions in the liver after hemorrhagic shock in the rat. AB - OBJECTIVE: To evaluate the influence of interleukin-1 on leukocyte-endothelial cell interactions and the microcirculation in the liver after hemorrhagic shock by means of intravital microscopy using an interleukin-1 receptor antagonist (IL 1ra). DESIGN: Prospective, randomized, blinded, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized female Sprague Dawley rats weighing 200 to 230 g. INTERVENTIONS: Hypovolemic shock was induced and maintained for 1 hr (mean arterial pressure 40 mm Hg; cardiac output 50% of baseline). After adequate resuscitation and 5 hrs of reperfusion (mean arterial pressure > 100 mm Hg; cardiac output > 120% of baseline), the microcirculation in liver sinusoids was examined by intravital fluorescence microscopy. Continuous administration of IL-1ra (5 mg/kg/hr) was started at different times in a prospective, randomized, blinded fashion, either as pretreatment 5 mins before shock induction (n = 6), or as therapy at the time of resuscitation (n = 6). An additional bolus injection of 5 mg/kg of IL-1ra was given to the latter group. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, cardiac output, heart rate, and blood gases were comparable in all shock groups during the experiments. The percentage of permanently adherent leukocytes (adhesion time of > 20 secs) in the pretreated group was significantly decreased in comparison with the control group (pretreatment group 16.9 +/- 1.9% vs. control group 42.1 +/- 5.4%; p < .001 by analysis of variance; sham group 9.1 +/- 1.1%). Administration of IL-1ra at the time of resuscitation also reduced firm adhesion of leukocytes to sinusoidal endothelium (treated group 28.8 +/- 3.6%, p < .01). Temporary adhesion rates of leukocytes (adhesion time of < 20 secs) were unaffected by pretreatment or treatment with IL-1ra with respect to control values. Liver microcirculation was impaired after hemorrhagic shock but not improved by IL-1ra. CONCLUSIONS: The results show that adhesion of leukocytes to hepatic sinusoidal endothelium is at least partly regulated by interleukin-1. Adherence was attenuated by the application of IL-1ra, which might be due to diminished expression of adhesion receptors by endothelial cells or leukocytes. Even administration of IL-1ra at the time of resuscitation reduces the early inflammatory response in the liver after shock, thus offering a potentially important therapeutic approach. PMID- 7774223 TI - Methyl isobutyl amiloride delays normalization of brain intracellular pH after cardiac arrest in rats. AB - OBJECTIVE: The sodium/hydrogen ion (Na+/H+) antiporter system of brain cells is responsible for reducing intracellular acid loads and regulating cellular volume. Activation of this system during reperfusion following cardiac arrest may contribute to cerebral edema and subsequent brain damage. Therefore, we wished to determine whether administration of methyl isobutyl amiloride, a known inhibitor of the Na+/H+ antiporter system, would cross the blood brain barrier and delay the return of brain intracellular pH to normal values during reperfusion after cardiac arrest in rats. DESIGN: a) Prospective sequential evaluation of the regional brain blood flow and 3H-methyl isobutyl amiloride extraction fraction in rats; b) prospective sequential evaluation of brain intracellular pH in rats treated with methyl isobutyl amiloride compared with untreated control rats. SETTING: A research laboratory. SUBJECTS: Thirteen male Wistar rats: a) three rats to study regional brain blood flow and 3H-methyl isobutyl amiloride cerebral extraction; and b) ten rats to study the effect of methyl isobutyl amiloride on brain intracellular pH after cardiac arrest and reperfusion. INTERVENTIONS: a) Rats were injected with 14C iodoantipyrine and 3H-methyl isobutyl amiloride, and their brains were subsequently analyzed to determine regional cerebral blood flow and percent of cerebral extraction of methyl isobutyl amiloride. b) Cardiac arrest was induced with potassium chloride followed by resuscitation 7 mins later in untreated control rats and rats treated with methyl isobutyl amiloride. MEASUREMENTS AND MAIN RESULTS: a) Regional cerebral blood flow (mL/100 g/min) determined with 14C iodoantipyrine and percent of cerebral extraction of 3H methyl isobutyl amiloride were evaluated in various regions of the brain. Mean +/ SD values were 167 +/- 15 and 7 +/- 1 for the frontal cerebral cortex; 159 +/- 10 and 7 +/- 2 for the parietal cerebral cortex, 130 +/- 17 and 8 +/- 1 for the hippocampus, 154 +/- 33 and 13 +/- 4 for the cerebellum and 166 +/- 27 and 6 +/- 1 for the striatum (mL/100 g/min). These values were determined by a dual label indicator fractionation method. b) Brain intracellular pH was measured by neutral red histophotometry after 15 mins of reperfusion following cardiac arrest. As compared with untreated control rats, methyl isobutyl amiloride-treated animals had significantly lower brain intracellular pH values after 15 mins of reperfusion. Mean +/- SD pH values were 6.78 +/- 0.18 for the rats treated with methyl isobutyl amiloride vs. normal intracellular pH of 7.11 +/- 0.07 for the untreated control rats. CONCLUSIONS: a) Methyl isobutyl amiloride crosses the blood brain barrier of rats. b) The Na+/H+ antiporter system is operative during reperfusion after cardiac arrest in rats. PMID- 7774224 TI - Serotonin receptors regulate canine regional vasodilator responses to burn. AB - OBJECTIVE: To determine which serotoninergic receptor subtype(s) mediates the regional vasodilator response to scald injury. DESIGN: Prospective, randomized trial. SETTING: Microcirculation research laboratory. SUBJECTS: Anesthetized dogs. INTERVENTIONS: Mechanically ventilated dogs underwent cannulation of a brachial artery and placement of an ultrasonic flow probe around one femoral artery. All animals received a 2% to 3% body surface area partial thickness scald injury by immersing the paw ipsilateral to the instrumented femoral artery into 100 degrees C water for 5 secs. In one group of dogs, BMY 7378 (a serotoninergic1A receptor antagonist) was given by the peripheral intravenous route before burn. These results were compared with those findings obtained from a group of animals that received a burn only, and groups of animals given a peripheral intravenous injection of methysergide (a serotoninergic receptor antagonist) or ritanserin (a serotoninergic2 receptor blocking agent) before burn. Experiments were conducted for two postburn hours. MEASUREMENTS AND MAIN RESULTS: Burn injury caused a marked and persistent increase in regional (e.g., femoral artery) blood flow, an effect that was significantly blunted by preburn administration of the serotoninergic receptor antagonist, methysergide. Preburn administration of BMY 7378 increased baseline femoral blood flow by 13%, reflecting its known serotonin agonist properties. However, when compared with the mean postscald increases in femoral blood flow over baseline seen in scald only dogs and in animals given the serotoninergic2 receptor blocking agent, ritanserin (before scald), the BMY 7378-treated group demonstrated a significant (p < .001 by analysis of variance) 2-hr-postscald blunting of this femoral vasodilator response. CONCLUSION: These data suggest that serotoninergic1A-like receptors play an integral, albeit not an exclusive, role in blood flow regulation to the site of burn injury. PMID- 7774225 TI - Simple method to measure total expiratory time constant based on the passive expiratory flow-volume curve. AB - OBJECTIVE: In intubated, mechanically ventilated patients, inspiration is forced by externally applied positive pressure. In contrast, exhalation is passive and depends on the time constant of the total respiratory system. The expiratory time constant is thus an important determinant of mechanical ventilation. The aim of this study was to evaluate a simple method for measuring the expiratory time constant in ventilated subjects. DESIGN: Prospective study using a lung simulator and ten dogs. SETTING: University hospital. SUBJECTS: Commercially available lung simulator and ten greyhound dogs. INTERVENTIONS: Different expiratory time constants were set on the lung simulator. In the dogs, the endotracheal tube was clamped to increase airways resistance by 22.5 cm H2O/(L/sec) and the lungs were injured with hydrochloric acid to decrease total respiratory compliance by 16 mL/cm H2O. This procedure resulted in a wide range of expiratory time constants. MEASUREMENTS AND MAIN RESULTS: Pneumotachography was used to measure flow and volume. The ratio of exhaled volume and peak flow was calculated from these signals, corrected for the limited exhalation time yielding the "calculated expiratory time constant" and compared with the actual expiratory time constant. The typical error was +/- 0.19 sec for the lung simulator and +/- 0.15 sec for the dogs. CONCLUSIONS: The volume and peak flow corrected for limited exhalation time is a good estimate of the total expiratory time constant in passive subjects and may be useful for the titration of mechanical ventilation. PMID- 7774226 TI - Serial somatosensory and brainstem auditory evoked potentials in monitoring of acute supratentorial mass lesions. AB - OBJECTIVE: To determine the relevance of serial evoked potentials (brainstem auditory evoked potentials and somatosensory evoked potentials) and clinical parameters (pupillary response and intracranial pressure) in patients with acute supratentorial mass lesions. DESIGN: Prospective case series of comatose patients with acute supratentorial mass lesions. SETTING: Neurocritical care unit of a tertiary care center. PATIENTS: Thirty consecutive patients with the following study inclusion criteria: a) clinical and computed tomography evidence of an acute supratentorial mass lesion; b) implantation of an intracranial pressure monitoring device; and c) a persistent comatose state during the observation period. INTERVENTIONS: Brainstem auditory evoked potentials, somatosensory evoked potentials, intracranial pressure, and pupillary responses were recorded at the time of three particular events: a) immediately after implantation of an epidural intracranial pressure monitoring device; b) during intracranial pressure therapy; and c) at termination of intracranial pressure therapy. Evoked potential results were ranked into three categories: a) normal on both sides; b) abnormal or absent on one side; and c) evoked potentials on both sides abnormal or absent. Spearman's rank correlation was performed to analyze serial recordings. Cross tables were generated to determine the prognostic value of evoked potentials and clinical parameters. Fisher's exact test was applied to calculate statistical significance. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure values correlated with pupillary responses and brainstem auditory evoked potentials during and at the termination of intracranial pressure therapy. Pupillary findings correlated with brainstem auditory evoked potentials only at the time of termination of intracranial pressure therapy. There was no correlation between somatosensory evoked potentials and clinical parameters. Pupillary responses indicated a good or poor recovery during and at the termination of intracranial pressure therapy. Brainstem auditory evoked potentials and intracranial pressure values distinguished between good and poor outcome only at termination of intracranial pressure therapy. Somatosensory evoked potential results did not predict outcome. CONCLUSIONS: Shortly after manifestation of supratentorial mass lesions, the results of evoked potentials and clinical parameters indicate increased intracranial pressure and incipient transtentorial herniation but do not predict sequelae. Our results indicate that after institution of effective therapy, pupillary abnormalities and brainstem auditory evoked potentials serve as valuable prognostic predictors. In contrast, somatosensory evoked potentials reflect neither therapeutic efficacy nor outcome in our patient population. PMID- 7774227 TI - Probability of survival after prolonged extracorporeal membrane oxygenation in pediatric patients with acute respiratory failure. Extracorporeal Life Support Organization. AB - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for respiratory failure that is unresponsive to conventional therapy. We examined the relationship between duration of ECMO and outcome to understand whether prolonged ECMO (duration of the procedure for > 14 days) was more commonly associated with futile therapy or eventual recovery. DESIGN: A cohort study of all patients reported to the Pediatric ECMO Registry for Acute Respiratory Failure of the Extracorporeal Life Support Organization. SETTING: Tertiary hospitals (n = 83) capable of providing extracorporeal support for pediatric patients. PATIENTS: Children (n = 382) between the ages of 1 wk and 18 yrs of age with severe respiratory failure. INTERVENTIONS: Extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: The death or live hospital discharge of ECMO-treated patients, together with the post-ECMO mechanical ventilation course, were examined as a function of duration of ECMO and of pre ECMO respiratory status. The occurrence of complications and the causes of death were also noted. The criteria used to initiate ECMO, as well as the determination of the futility of further ECMO, were determined by local practice at individual centers. There were 382 patients treated with ECMO, of whom 184 (48%) survived. The proportional survival in the patients treated for the longest duration was similar to the overall group. The cause of death was given for 168 patients: 32 neurologic deaths; nine deaths due to ECMO complications; and 30 deaths due to nonpulmonary organ failure. There were 97 deaths due to elective ECMO termination; 80 of these deaths occurred after the determination of the futility of anticipating pulmonary recovery. The latter deaths occurred at widely varying durations of ECMO, with a median of 282 hrs. However, at that same duration, 47 eventual survivors (26% of all survivors) continued to receive ECMO. By discriminant analysis, the survival rate was independently related (r2 = .18; p < .0001) to peak ventilator inspiratory pressure before ECMO and duration of intubation before ECMO, patient age, and the occurrence of several complications. CONCLUSIONS: While the survival rate in pediatric patients receiving ECMO appears related to the severity of lung disease and to the occurrence of ECMO complications, the survival rate in patients treated with ECMO courses of > 2 wks was similar to the survival rate of patients treated for shorter periods of time. ECMO was terminated in some patients for pulmonary futility at durations of ECMO associated with survival in substantial numbers of patients in whom ECMO was continued. PMID- 7774229 TI - Coma and metabolic acidosis related to the use of muscle liniment. PMID- 7774228 TI - Noninvasive monitoring of end-tidal carbon dioxide tension via nasal cannulas in spontaneously breathing children with profound hypocarbia. AB - OBJECTIVE: To determine the correlation between end-tidal CO2 and PaCO2 measured via nasal cannulas in spontaneously breathing children with profound hypocarbia (PaCO2 < 30 torr [< 4.0 kPa]). DESIGN: Prospective evaluation. SETTING: Pediatric intensive care unit (ICU) in a tertiary care referral center. INTERVENTIONS: None. PATIENTS: Patients admitted to the ICU with a diagnosis of diabetic ketoacidosis in whom invasive arterial access was deemed necessary for clinical care. The patients were spontaneously breathing, without intubation. The study included nine patients, with an average age of 9.9 yrs (range 4 to 17) and weight of 38.7 kg (range 17 to 68). MEASUREMENTS AND MAIN RESULTS: End-tidal CO2 was sampled from nasal cannulas by a sidestream aspirator and estimated by infrared spectroscopy. The correlation between arterial and end-tidal CO2 was compared using linear regression analysis. A total of 65 arterial blood gases were obtained from the nine patients. The PaCO2 was < or = 30 torr (< or = 4.0 kPa) in 38 of the samples. The PaCO2 to end-tidal CO2 gradient was < or = 4 torr (< or = 0.5 kPa) in 64 of 65 samples and 4.8 torr (0.6 kPa) in one sample. Linear regression analysis of arterial vs. end-tidal CO2 yielded a slope of 0.99, an r2 value of .97, and a p value of .0001. CONCLUSIONS: End-tidal CO2 measurement by infrared spectroscopy provides an accurate estimation of PaCO2, even during episodes of severe hypocarbia. Its use may limit the need for invasive monitoring and/or repeated arterial blood gas analyses. PMID- 7774230 TI - Clostridium difficile causing sepsis and an acute abdomen in critically ill patients. PMID- 7774231 TI - Lorazepam versus midazolam for sedation. PMID- 7774232 TI - Lorazepam versus midazolam for sedation. PMID- 7774233 TI - Regionalization of critical care medicine. PMID- 7774234 TI - Prolonged paralysis with atracurium infusion. PMID- 7774235 TI - Prolonged paralysis with atracurium infusion. PMID- 7774236 TI - Another negative clinical trial of a new agent for the treatment of sepsis: rethinking the process of developing adjuvant treatments for serious infections. PMID- 7774237 TI - Medical management of aneurysmal subarachnoid hemorrhage. PMID- 7774239 TI - Preserving preceptors: a valuable resource. PMID- 7774238 TI - A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. AB - OBJECTIVE: To evaluate the safety and efficacy of E5, a murine, monoclonal antibody directed against endotoxin, in the treatment of patients with Gram negative sepsis. DESIGN: A multicenter, randomized, double-blind, placebo controlled trial. SETTING: Fifty-three hospitals across the United States, including university medical centers, Veterans Affairs Medical Centers, and community hospitals. PATIENTS: 847 patients were randomized into this study. Enrolled patients met criteria for three conditions: a) known or suspected Gram negative infection; b) clinical evidence of sepsis; and c) signs of end-organ dysfunction. Patients with refractory shock were excluded from the study. INTERVENTIONS: Two doses of E5 (2 mg/kg/day by intravenous infusion 24 hrs apart), or placebo that was identical in appearance were administered. In addition, all patients received standard supportive therapy and broad-spectrum antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary end point was mortality over 30 days. Secondary outcome measures included the resolution and prevention of organ failure in the same two populations. Additionally, the safety of E5 was evaluated. There was no significant improvement in survival over 30 days among patients with Gram-negative sepsis who received E5 compared with those patients who received placebo (n = 530; p = .21). In addition, E5 did not improve survival for patients with Gram-negative sepsis and organ failure (n = 139; p = .3). However, a significantly greater percentage of patients with Gram-negative sepsis experienced resolution of major organ failure if they received E5, compared with those patients who received placebo (n = 139; 48% E5 vs. 25% placebo; p = .005). This result extended to all patients who entered the study with one or more major organ failures, regardless of the etiology of the infection (n = 225; 41% E5 vs. 27% placebo; p = .024). E5 also provided protection against the development of some organ failures, but significant prevention was only observed for adult respiratory distress syndrome (p = .007) and central nervous system dysfunction (p = .050). Hypersensitivity reactions attributable to E5 occurred in 2.6% of patients. An asymptomatic antibody response occurred in 44% of the E5-treated patients and in 12% of the patients who received placebo. CONCLUSIONS: In this study, E5 did not reduce mortality in nonshock patients with Gram-negative sepsis whether or not those patients also had organ failure. However, E5 did result in greater resolution of organ failure in patients with Gram-negative sepsis. This benefit extended to those patients with suspected Gram-negative etiology. This finding is important because patients with suspected Gram-negative sepsis and organ failure can be identified without waiting for culture results. In addition, E5 resulted in the prevention of adult respiratory distress syndrome and central nervous system organ failure. However, more studies are needed to determine if this result can be extended to organ failure in general. E5 is safe as a treatment for patients with Gram-negative sepsis. PMID- 7774240 TI - The patient-driven system. PMID- 7774241 TI - Playing--and winning--the transitions game. PMID- 7774242 TI - Winners and losers in healthcare reform. PMID- 7774244 TI - Innovations in technology: continuous intra-arterial blood gas monitoring. PMID- 7774243 TI - Clarification sought for pharmacologic stress testing. PMID- 7774245 TI - Auto-PEEP: measurement issues and nursing interventions. PMID- 7774246 TI - Measles pneumonia in the critically ill child: application of alternative ventilation strategies. AB - Measles pneumonia is a life-threatening complication in children infected with the measles virus. The increased number of reported cases over the last several years suggests a need for heightened awareness of the complication among pediatric critical care nurses. Application of alternative ventilation strategies in the critical care setting continues to be explored in children with ARDS refractory to more conventional ventilation support, because the mortality and morbidity associated with ARDS in children remain high. Patients who present with diffuse, bilateral lung injury, such as in measles pneumonia, may be candidates for alternative ventilation strategies. Few investigators have studied alternative ventilation strategies in the pediatric ICU setting. Therefore, nursing research related to the impact of nursing interventions during alternative ventilation strategies is needed. Specifically, evaluation of ET suctioning practices and other interventions that influence oxygen delivery and consumption are necessary to plan effective care during alternative ventilation strategies and improve patient outcome. Prevention of measles pneumonia is clearly the preferred "treatment." Preventive healthcare is paramount in providing optimal care for children. However, until we can address the environmental factors that predispose children to communicable diseases such as measles, critical care nurses must be knowledgeable about the assessment and management of measles pneumonia. PMID- 7774247 TI - ECCO2R: an experimental approach to treating ARDS. PMID- 7774248 TI - Factors related to unplanned extubation of endotracheal tubes. PMID- 7774249 TI - Continuous airway pressure monitoring in the critical care setting. PMID- 7774250 TI - Critical care technicians: letting nurses be nurses. Interview by Michael Villaire. PMID- 7774252 TI - AACN believes in ... bridging the gap between research and practice. PMID- 7774251 TI - Critical care nursing in army field hospitals. PMID- 7774253 TI - AACN believes in ... partners in the community. PMID- 7774254 TI - AACN believes in ... helping people make care choices. PMID- 7774255 TI - AACN believes in ... helping nurses learn. PMID- 7774256 TI - AACN believes in ... programs driven by the needs of patients. PMID- 7774257 TI - Jill Ley: putting critical pathways on the map. Interview by Michael Villaire. PMID- 7774258 TI - Strategies for writing an effective resume. PMID- 7774259 TI - The supervisory status of nurses. PMID- 7774260 TI - Accreditation aches and pains. PMID- 7774261 TI - Care: an ethical foundation for critical care nursing. AB - Critical care nursing by definition focuses on human responses to life threatening problems. An increasing number of ethical dilemmas confronts the critical care nurse. A traditional principled orientation to ethical reasoning requires detachment that does not acknowledge the special nature of the nurse patient relationship and, by itself, does not give satisfactory direction in resolving ethical dilemmas. An ethic of care that acknowledges the special relationship and connection of one human being with another may provide the necessary guidance to assist the nurse in resolving these dilemmas. Critical care nursing practice based on an ethic of care acknowledges and legitimizes care for patients as well as oneself. PMID- 7774262 TI - The patient-driven system. PMID- 7774263 TI - A message to critical care nurses. PMID- 7774264 TI - A misconception in article on counting heart rate? PMID- 7774265 TI - Manipulating PA catheters carries responsibility. PMID- 7774266 TI - Coronary-subclavian steal after CABG surgery. AB - Patients who have undergone CABG surgery using the IMA are at risk for the development of coronary-subclavian steal. Therefore, recurrence of angina or ECG signs suggestive of myocardial ischemia after CABG with the IMA must be evaluated immediately. Recognition of the signs and symptoms with appropriate intervention is necessary to prevent the life-threatening consequences of reversed bloodflow from the myocardium. Routine assessment of bilateral blood pressure measurements may provide a critical clue in identifying this syndrome. PMID- 7774267 TI - Rupture of a splenic artery aneurysm in pregnancy. AB - Although ruptured splenic artery aneurysm in pregnancy is frequently fatal for mother and infant, prompt diagnosis and surgical treatment increase their chances for survival. Normal physiologic and hemodynamic changes of pregnancy may mask early symptoms of hypovolemic shock in pregnant women. The fetus is especially at risk, because maternal compensatory mechanisms activated during hemorrhage shunt blood from uteroplacental circulation to maternal central circulation. Collaboration between perinatal and critical care team members is essential. PMID- 7774268 TI - Acute methemoglobinemia: a nursing perspective. PMID- 7774269 TI - Is chest physiotherapy necessary after cardiac surgery? PMID- 7774270 TI - Genetic illness in the adult ICU: implications for nursing practice. PMID- 7774271 TI - Managing coronary atherectomy patients in a special procedure unit. PMID- 7774272 TI - Peripheral nerve stimulators in the critical care setting: a policy for monitoring neuromuscular blockade. PMID- 7774273 TI - Nursing care of patients undergoing dynamic cardiomyoplasty. PMID- 7774274 TI - What heals? What do nurses do that makes a difference? PMID- 7774275 TI - Gastroesophageal reflux: the use of pH monitoring. PMID- 7774276 TI - Perforin and granzymes: crucial effector molecules in cytolytic T lymphocyte and natural killer cell-mediated cytotoxicity. PMID- 7774278 TI - TIA-1: structural and functional studies on a new class of cytolytic effector molecule. PMID- 7774277 TI - Perforin, killer cells and gene transfer immunotherapy for cancer. PMID- 7774279 TI - Calreticulin: a granule-protein by default or design? PMID- 7774280 TI - A new function for an old enzyme: the role of DNase I in apoptosis. PMID- 7774281 TI - The ligands and receptors of the lymphotoxin system. PMID- 7774283 TI - The role of CD28 costimulation in the generation of cytotoxic T lymphocytes. PMID- 7774282 TI - Structure and biogenesis of lytic granules. AB - Lytic granules are specialized secretory organelles which appear after activation of CTLs and NK cells. The lytic granules contain a series of proteins that mediate target cell destruction after secretion from the cell. In addition, these organelles serve as the lysosomes of these lymphocytes. At the EM level three types of granules with distinct regions are distinguished. Intriguingly, lytic and lysosomal proteins are localized in distinct regions. This is particularly interesting because lysosomal and lytic proteins can use the same sorting mechanisms to be targeted to this compartment. We favor the idea that a combination of sorting mechanisms result in this final segregation: the MPR receptor sorts both lysosomal proteins and granzymes from the Golgi complex, but a second event, such as selective aggregation with proteoglycans, then results in the segregation of lytic and lysosomal proteins in the granule. Lytic granules provide a way to store and simultaneously secrete the lytic proteins in a highly specific fashion. The granules are able to move along microtubules using a kinesin-like motor, and thus can cluster at the site of membrane contact with a target cell. Once polarized, the granules exocytose their contents, using a molecular machinery that is as yet poorly defined. Understanding the machinery involved in both functions of the lytic granules will provide ways to control the action of cytotoxic lymphocytes, ultimately in clinical situations. PMID- 7774284 TI - Degranulating cytotoxic lymphocytes inflict multiple damage pathways on target cells. PMID- 7774285 TI - Granzymes and apoptosis: targeting the cell cycle. PMID- 7774286 TI - Effects of vasoactive intestinal polypeptide on the growth processes in rat thyroid lobes: studies ex vivo in vitro. AB - The effects of intravenous (i.v.) injections of vasoactive intestinal polypeptide (VIP) and intraperitoneal (i.p.) injections of thyroid-stimulating hormone (TSH, thyrotropin) on 3H-thymidine incorporation into the DNA of rat thyroid lobes incubated, after collecting, in vitro, were investigated. The animals of groups 1 6 were injected with the following substances: group 1, 0.9% NaCl; group 2, 2 IU TSH (i.p.); group 3, 10(-12) mol VIP; group 4, 10(-10) mol VIP; group 5, 10(-8) mol VIP; and group 6, 10(-8) mol VIP + 2 IU TSH (i.p.). The rats of each group were divided into three subgroups, and sacrificed after 6, 12 or 24 h from the time of injection. For group 1, the additional control group zero was used, and these controls were sacrificed immediately after i.v. injections of 0.9% NaCl at zero time. After decapitation the thyroid lobes were collected and then incubated for 4 h in RPMI 1640 medium in the presence of 3H-thymidine, 15% FCS and Hepes buffer. In all groups and at all times an increase of 3H-thymidine incorporation occurred; the stimulatory effect of VIP (in all doses) was stronger than that of TSH; the rate of 3H-thymidine incorporation after injections of both VIP and TSH (group 6), was higher than the rates following injections of VIP alone (group 5) or TSH alone (group 2). PMID- 7774287 TI - Age-associated changes of neutrophil responsiveness in a human healthy elderly population. AB - Conflicting results have been reported on polymorphonuclear (PMN) cell responsiveness during senescence. Consequently, neutrophil absolute numbers and PMN-mediated chemotaxis, phagocytosis, killing and superoxide anion (O2-) generation in healthy aged volunteers divided into different groups according to increasing age criteria, were investigated and evaluated. Data provide evidence that absolute amounts of PMN cells declined in a significant manner in donors over 85 years old only when compared with young subjects. On the contrary, regardless of age, the aged individuals exhibited a significant impairment of PMN chemotactic, phagocytic and killing functional capacities. Finally, formyl methionyl-leucyl-phenylanaline (FMLP)-triggered O2- release was reduced in all elderly groups, while depression of O2- production was seen in subjects between the age of 86 and 104 years using phorbol 12-myristate 13-acetate (PMA) as agonist. These findings indicate that an imbalance in the PMN cell immune reactivity occurs throughout the senescence process. PMID- 7774288 TI - Transformation of diploid human lung fibroblasts with oncogene ras increases the frequency of abnormal mitoses. AB - The human oncogene ras p21 was transfected into human lung fibroblast WI-38 diploid cells. All of the clones that were isolated (n = 36), exhibited rapid growth and transformed morphology which was ascertained by both transmission and scanning electron microscopy as extensive formations of microvilli on the plasma membrane, marked distortion of the nuclear membrane and increased number of pinocytotic vesicles in the cortical cytoplasm. The frequency of abnormal metaphases rose from 15% in parental WI-38 cells to 35.5-48.4% in all ten clones examined. Lagging chromosomes in prometaphase represented 42.1-69.4% of the total abnormal mitoses followed in frequency by 3-group metaphase and C-metaphase. All transformed cells were aneuploid. These data provide evidence for the association between cellular transformation with oncogenic ras and elevated abnormal mitoses in human cells. PMID- 7774289 TI - Localization of the Cu/Zn superoxide dismutase gene in the Drosophila willistoni species group by in situ hybridization. AB - Due to the physiological importance of its product, the Cu/Zn superoxide dismutase enzyme, the gene coding for this enzyme was mapped in five species of the Drosophila willistoni subgroup and in D. nebulosa by in situ hybridization using D. melanogaster as a control. The results indicate that this locus is located on the XR chromosomal arm of the five sibling species and on the XL chromosomal arm of D. nebulosa, suggesting the occurrence of a pericentric inversion before the separation of these entities. PMID- 7774291 TI - Accumulation of B-chromosomes in drosophila kikkawai Burla. AB - Drosophila kikkawai is a unique species in the genus, having two types of B chromosomes with distinct centromeres. Laboratory experiments pertaining to their accumulation were carried out, using continuous selection and inbreeding procedures. Karyotypes with B-chromosomes ranged from 1 to 4. A maximum of four B chromosomes in a culture were accumulated which seems to be the maximum tolerable limit in this species. PMID- 7774290 TI - Vitamin C mediated amelioration of pesticide genotoxicity in murine spermatocytes. AB - The effect of vitamin C on the genotoxicity of three pesticides (Endosulfan, Phosphamidon, Mancozeb) was monitored by screening meiotic (metaphase I) chromosomes in the primary spermatocytes of Swiss albino mice, Mus musculus. A dose-dependent amelioration by vitamin C was observed in the Phosphamidon-treated group where quadruple the therapeutic dose produced maximum amelioration. In Endosulfan- and Mancozeb-treated groups, no further amelioration was achieved beyond the double dose of vitamin C, and the damage frequency did not come down to the control level. The possible mechanism of this effect is discussed. PMID- 7774292 TI - Practicing medicine without a license. PMID- 7774293 TI - Beta 2-agonists and their antagonists. PMID- 7774294 TI - Is thoracic CT performed often enough? PMID- 7774295 TI - In search of the appropriate use of chest computed tomography. PMID- 7774296 TI - Is living kidney donation still justifiable? PMID- 7774297 TI - Aerosol therapy in mechanically ventilated patients. PMID- 7774298 TI - Nd-YAG laser pleurodesis via thoracoscopy. Endoscopic therapy in spontaneous pneumothorax Nd-YAG laser pleurodesis. AB - From January 1986 to February 1993, 85 patients with spontaneous pneumothorax were treated in our department by a new endoscopic procedure using an Nd-YAG laser beam via thoracoscopy to obtain permanent pleurodesis and to treat the lung lesion responsible for the air leak. The 55 men and 30 women ranged in age from 16 to 51 years (mean age 26 years). Under general anesthesia the thoracoscope was introduced through a 1-cm incision in the anterior axillary line of the fourth intercostal space. In 68 patients small blebs (less than 2 cm in diameter) were detected and successfully resected with low power Nd-YAG laser pulses. In two patients found at thoracoscopy to have lesions larger than 2 cm, the Nd-YAG laser failed to seal the air leak and thoracotomy was performed. Air leaks were not detected at endoscopy in the remaining patients. After treatment of the lung lesions, the parietal pleura was abraded by using the laser energy. There were no side effects. Eighty patients were treated successfully without recurrence (maximum follow-up 86 months). Three other patients developed recurrence of pneumothorax after 5, 6, and 24 weeks, and surgery was considered mandatory in 2 of them. At thoracotomy, in both patients, a small bleb was detected in the lower lobe and resected. The whole upper lobe was strongly adherent to the parietal pleura in the site of previous laser abrasion. The authors conclude that Nd-YAG laser via thoracoscopy should be considered as a viable therapeutic option in patients with spontaneous pneumothorax. PMID- 7774299 TI - Pleurodesis using talc slurry. AB - OBJECTIVE: To determine the efficacy and safety of talc slurry for pleurodesis. DESIGN: Retrospective. PARTICIPANTS: All patients who received talc slurry via tube thoracostomy at Memorial Sloan-Kettering Cancer Center from March 1991 to April 1992. RESULTS: Fifty-eight patients received talc slurry in 75 procedures; five patients had 2 unilateral procedures and 12 had bilateral procedures. Fifty two patients had malignant pleural effusions with the most common cell types being breast (23 of 52, 44 percent), lung (4 of 52, 8 percent), ovarian (4 of 52, 8 percent), and endometrial (3 of 52, 6 percent). Four patients had benign conditions. The mean duration of follow-up was 171 days (range, 2 to 450 days). Success, defined as the absence of pleural fluid reaccumulation, was evaluable in 47 of 73 (64 percent) procedures. Pleurodesis was successful in 38 of 47 (81 percent). Adverse effects associated with pleurodesis included fever (46 of 73, 63 percent), empyema (4 of 73, 5 percent), atrial arrhythmia (3 of 73, 4 percent), hypotension (3 of 73, 4 percent), and hypoxemic respiratory failure (3 of 73, 4 percent). There were no deaths attributable to the procedure. CONCLUSIONS: Talc slurry instilled through a chest tube is an effective bedside method of pleurodesis. Fever occurs frequently. Respiratory failure is a rare but potentially serious complication that deserves further investigation. PMID- 7774300 TI - Spontaneous pneumothorax. Long-term results with tetracycline pleurodesis. AB - The aim of this prospective study was to determine the rate of recurrence for spontaneous pneumothorax (SP) after tetracycline pleurodesis (TCP), using that of observation, tube thoracostomy alone, and thoracotomy as references. From 1985 to the end of 1991, 78 patients were treated with tetracycline pleurodesis and 135 patients served as control subjects. Pleurodesis was induced by instillation of tetracycline and ascorbic acid through the pleural drain. The indication was any SP treated with tube thoracostomy, without active pulmonary infection. Follow-up period was from 13 to 95 months (mean, 45 months); follow-up rate was 94 percent. Post-therapy surgery was necessary for eight patients in whom pleurodesis failed due to presence of a persistent air leak. The ipsilateral recurrence rate of patients treated with TCP was 9 percent (6/66) and recurrence time ranged from 2 days to 9 months. The recurrence rate for patients treated with observation was 36 percent, 35 percent for those having chest tube alone, and none for those undergoing surgery. No death occurred as a direct result of this procedure and all patients could be released from the hospital. Eleven subjects died during the follow-up period; the mean follow-up until death was 37 months (range, 2 to 87 months). Five deaths were due to respiratory causes and six were due to extrapulmonary causes. Tetracycline pleurodesis has been shown to be a good alternative for the prevention of recurrence of SP. Its recurrence rate is lower than that of tube drainage but higher than that of surgical treatment. PMID- 7774301 TI - Subclinical surface alterations of human pleura. A scanning electron microscopic study. AB - Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells. PMID- 7774302 TI - Cardiopulmonary exercise testing. Determinants of dyspnea due to cardiac or pulmonary limitation. AB - The aim of this study was to bring to light new and simple criteria, obtained during cardiopulmonary exercise testing, in order to demonstrate in patients the cardiac or the pulmonary origin of a comparable exertional dyspnea. Forty male subjects were compared, who exercised with a 30-W/3-min protocol and were divided into three groups: the cardiac heart failure (CHF) group (n = 15), the chronic obstructive lung disease (COLD) group (n = 15), and the control group (n = 10). The two groups of patients differed totally from the control group concerning their spirometric values at rest and a clear inability during effort which was confirmed by all the studied cardiopulmonary parameters at maximal exercise. The CHF and COLD groups differed slightly concerning their maximum symptom-limited oxygen uptake, only when related to body mass (13.26 +/- 0.69 ml/kg/min in CHF group, 17.05 +/- 1.59 ml/kg/min in COLD group; p < 0.05), and concerning their maximum ventilatory equivalent for oxygen which tended to be higher in the CHF group in comparison with the COLD group (p = 0.082). Furthermore, and as foreseen, the two groups of patients clearly differed at maximum exercise concerning the ventilatory reserve respiratory parameter (49.73 +/- 3.18 percent in CHF group, 8.38 +/- 5.85 percent in COLD group; p < 0.01). On the other hand, they did not differ concerning cardiac parameters or those considered as such (maximum heart rate [HR], HR reserve, HR response, maximum O2 pulse measurement). While their maximum ventilation was similar in the CHF and COLD groups, a difference in adaptation during exercise was found by observing their breathing pattern. In the CHF group, this was demonstrated by a significantly lower breathing frequency at maximum exercise (31.24 +/- 1.53 beats/min vs 37.75 +/- 2.24 beats/min; p < 0.05) and a tidal volume that tended to be higher at maximum exercise (p = 0.077) and significantly higher at 60-W work load (p < 0.05). This work shows that the study of ventilatory reserve and breathing pattern during exercise testing allows one to discriminate if dyspnea on exertion in patients is due to cardiac or respiratory disease. PMID- 7774303 TI - The effects of exercise testing on the prescription of oxygen therapy. AB - This study reviews the effects of using oxygen saturation measurements during exercise and the effects of the method of exercise testing on the prescription of oxygen therapy. Using cutaneous oximetry (designated A and B models) and co oximetry, 25 of 41 patients (model A), 30 of 39 patients (model B), and 28 of 42 patients (co-oximetry) had an oxygen saturation measurement greater than 85 percent at maximal incremental exercise despite an arterial oxygen tension less than 55 mm Hg. Also, in a group of patients who underwent incremental followed by constant work rate testing, 9 of 28 exhibited a fall in arterial oxygen tension to 55 mm Hg or below only during the constant work rate testing. Oxygen saturation measurements cannot reliably be used as a substitute for arterial oxygen tension measurements for the prescription of oxygen therapy. The type of exercise study performed may influence the outcome of such oxygen prescription. PMID- 7774304 TI - The relationship between oxygen consumption and work rate in patients with airflow obstruction. AB - The oxygen cost of augmented ventilation is increased in patients with chronic obstructive pulmonary disease, either at rest or during exercise. Thus, if excessive demands are placed on the respiratory muscles during exercise in these patients, we postulate that the total oxygen consumption (VO2) may increase relative to the work rate compared to control subjects. The aim of this study was to examine the relationship between VO2 and work rate during exercise in patients with airflow obstruction. A retrospective analysis of data collected over 7 years was conducted. Patients with airflow obstruction (n = 131) were compared and contrasted with those in whom pulmonary function studies (spirometry, lung volumes) were normal (n = 199). Severity of airflow obstruction (ie, mild moderate, severe) was determined, using the 95 percent confidence limits for the ratio of FEV1 to FVC. Incremental exercise studies were performed on a cycle ergometer. Resting VO2 was not significantly different across the groups with airflow obstruction measured either directly or normalized for body weight. The VO2max was significantly reduced in the patients with severe airflow obstruction, compared with the normal group, as well as the patients with mild and moderate airflow obstruction. No differences were noted in the slope of VO2 plotted against work rate in the patients with airflow obstruction (regardless of the severity of the obstruction) and individuals in whom results of pulmonary function tests were normal. In addition, when gender was taken into account, there was essentially no difference in the slopes for either male or female subjects across all groups. Stepwise, linear regression failed to demonstrate any variable or variables that were strongly related to slope. We postulate that the maintenance of a normal slope of VO2 on work rate in patients with airflow obstruction, in whom the oxygen cost and work of breathing is likely increased, may mask a significant reduction in nonrespiratory VO2 (for example, to exercising skeletal muscles). PMID- 7774305 TI - Role of myocarditis in athletes with minor arrhythmias and/or echocardiographic abnormalities. AB - We report the clinical and instrumental data, including the endomyocardial biopsy findings, of six young athletes presenting with minor arrhythmias and/or echocardiographic abnormalities. In one of them, a left ventricular dilation with moderate depression of the systolic function had been attributed to an athlete's heart. A diagnosis of arrhythmogenic right ventricular dysplasia had been made in three others, one with right ventricular dilation and apical hypokinesia, and two with ventricular arrhythmias with QRS morphology of left bundle branch block. A myocarditis could be unequivocally established in four athletes (two with and two without fibrosis). In the remaining two, with a clinical history strongly suggesting a previously acute myocarditis, the endomyocardial biopsy specimen revealed a nonspecific fibrosis compatible but not definitely pathognomonic of a healed myocarditis. Our report suggests that a myocarditis may be a cause of minor rhythm disturbances and/or echocardiographic abnormalities in athletes. A prevalent localization of the inflammatory process in the right ventricle with or without the occurrence of ventricular arrhythmias with left bundle branch block morphology can mimic an arrhythmogenic right ventricular dysplasia. An early diagnosis of myocarditis in athletes is useful to avoid the risk of fatal arrhythmias, also considering that rest still keeps on being one of the most effective strategies in myocarditis management. PMID- 7774306 TI - Chest radiographs fail to detect right ventricular enlargement and right atrial enlargement in patients with a pure restrictive ventilatory impairment. AB - The validity of measurements of the cardiac silhouette on chest radiographs for the evaluation of right ventricular enlargement and right atrial enlargement in patients with a pure restrictive ventilatory impairment was investigated in 19 patients. The forced vital capacity (FVC) percent predicted in these patients was 59 +/- 12 percent (mean +/- SD) (range, 29 to 79 percent). Right ventricular enlargement, by two-dimensional echocardiography, was defined as a right ventricular area > 20.4 cm2 and right atrial enlargement was defined as a right atrial area > 15.3 cm2. Chest radiographic measurements in the posteroanterior (PA) projection included distance from the midline to the farthest point of the right border of the cardiac silhouette, transverse cardiac diameter, and cardiothoracic ratio. Measurements in the lateral projection included the lateral horizontal transverse diameter, ventral portion of the lateral broad diameter, and obliteration of the retrosternal space. Neither the right ventricular area nor the right atrial area correlated with any of these radiographic measurements. There were no differences in these chest radiographic measurements among patients with normal right ventricular and right atrial dimensions, patients with right ventricular enlargement, and patients with right atrial enlargement. We conclude, therefore, that PA and lateral chest radiographs do not reliably detect right ventricular enlargement or right atrial enlargement in patients with a pure restrictive ventilatory impairment. PMID- 7774307 TI - Paradoxic pulmonary vasoconstriction in response to acetylcholine in patients with primary pulmonary hypertension. AB - Pulmonary vascular reactivity was assessed during diagnostic heart catheterization in two patients with pulmonary hypertension unexplained by pulmonary or cardiac disease and in five patients with atypical chest pain and normal coronary arteriograms. Acetylcholine, an endothelium-dependent vasodilator that also has a direct contracting effect on vascular smooth muscle cells, was infused in the right atrium in a step-wise increasing dose in order to obtain final blood concentrations in the pulmonary circulation ranging from 10(-6) mol/L to 10(-4) mol/L. In the five control patients, acetylcholine induced a dose related decrease of pulmonary vascular resistance (-52 percent +/- 9 percent). In the patients with primary pulmonary arterial hypertension, however, acetylcholine caused a paradoxic increase of pulmonary arterial pressure and of pulmonary vascular resistance. Thus, it appears that endothelium-dependent vasodilation is impaired in the pulmonary circulation of patients with primary pulmonary arterial hypertension. Endothelial dysfunction in the pulmonary circulation may play a role in the pathophysiology of this disease. PMID- 7774308 TI - Stacked inspiratory spirometry reduces pulmonary shunt in patients after coronary artery bypass. AB - Atelectasis is a major factor in postoperative morbidity for patients undergoing cardiopulmonary surgery. We evaluated the effectiveness of stacked inspiratory spirometry (STIS) in 17 patients status postcoronary artery bypass graft in a nonrandomized fashion. We measured pulmonary shunt as an endpoint, and compared the magnitudes before and after the STIS maneuver. Our results showed an 8.66 percent reduction in pulmonary shunt (p < 0.05). The reduction in shunt was modest; however, repetitive maneuvers might result in greater improvement. PMID- 7774309 TI - Noninvasive predictors of systemic embolism in mitral stenosis. An echocardiographic and clinical study of 500 patients. AB - Few predictors of systemic embolism in patients with mitral stenosis have been identified by noninvasive methods. This study used the most powerful noninvasive diagnostic tool, transthoracic echocardiography, as well as other noninvasive clinical information to look for predictors. Five hundred consecutive patients with a mitral valve area of 2 cm2 or less were studied. They were divided into two groups: group 1 consisted of 143 patients with a history of systemic embolism and group 2 consisted of 357 patients with no history of systemic embolism. Using a stepwise logistic regression on a random subsample of 400 patients, 4 independent predictors were found: the presence of atrial fibrillation (p = 0.003, relative risk [RR] = 2.3, 95% CI = 1.3, 4.2), the absence of significant tricuspid regurgitation (p = 0.008, RR = 2.5, 95% CI = 1.3, 4.9), the absence of aortic regurgitation (p = 0.022, RR = 2.2, 95% CI = 1.1, 4.2), and the presence of left atrial smoky echoes (p = 0.039, RR = 1.7, 95% CI = 1.1, 3.0). When the above model, together with significant interaction terms, was applied to the remaining 100 patients, both the Hosmer-Lemeshow and Brown goodness-of-fit statistics were not significant (p = 0.888 and p = 0.248, respectively), indicating that the fit was adequate and the model was validated. Thus, important noninvasive predictors of systemic embolism in patients with mitral stenosis can easily be obtained. Subgroups of patients with high risk of systemic embolism can be identified. This may refine our therapeutic strategies to prevent the catastrophe of systemic embolism. PMID- 7774310 TI - Interleukin-2 and soluble interleukin-2 receptor in bronchoalveolar lavage fluid from patients with bronchial asthma. AB - To clarify the interrelation between interleukin-2 (IL-2) and soluble IL-2R receptor (sIL-2R), as products of T-cell activation in the bronchial tree of patients with bronchial asthma, we measured the concentration of IL-2, sIL-2R, and the cellular composition in bronchoalveolar lavage (BAL) fluid. We also measured physiologic parameters, including provocation concentration of histamine required to reduce the forced expiratory volume in 1 s by 20 percent of the prechallenge baseline (PC20). The concentrations of IL-2 and sIL-2R were higher in BAL fluid of symptomatic patients with bronchial asthma than those of normal subjects and asymptomatic patients. There was a significant correlation between IL-2 and sIL-2 concentrations in BAL fluid of the patients with bronchial asthma. Patients with other lung diseases had significantly higher concentration of IL-2 than normal control; however, sIL-2R was not detected in their BAL fluids. The concentration of IL-2 inversely correlated with FEV1 in symptomatic bronchial asthma. Among the inflammatory cells in BAL fluid, percentages of eosinophils showed significant correlation with the concentrations of IL-2 and sIL-2R in BAL fluid of the patients with bronchial asthma. In conclusion, IL-2 within the bronchial tree appears to be associated with eosinophil infiltration. This leads to physiologic changes in symptomatic patients with bronchial asthma, which may be influenced by the presence of sIL-2R in BAL fluid. PMID- 7774311 TI - Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis. AB - Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL 6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome. PMID- 7774312 TI - The role of two-segment bronchoalveolar lavage in the diagnosis of pulmonary infections. AB - STUDY OBJECTIVE: To determine if performing bronchoalveolar lavage (BAL) from more than one lung segment augments the diagnostic yield in patients with pulmonary infection. PATIENTS AND STUDY DESIGN: Seventy-six patients who underwent bisegmental BAL for the diagnosis or exclusion of pulmonary infection were studied prospectively. MAIN RESULTS: In patients with AIDS, the concentration of Pneumocystis carinii was higher in the upper lobes than in the middle lobes, regardless of whether the patients had been receiving pentamidine prophylaxis. In patients without HIV infection, the number of P carinii clusters was much lower. In 2 of 5 HIV-negative patients, P carinii organisms were detectable but in one of two lavage specimens, whereas in only 1 of 19 AIDS patients, P carinii organisms were not found in both lavaged segments. In bacterial pneumonia, BAL fluid from a segment of the radiologically most involved area had a much higher cell concentration, percentage of neutrophils, and concentration of bacteria than from the segment that was not or less severely involved on chest radiograph. In two of nine patients with AIDS and cytomegalovirus (CMV) pneumonia, cytopathogenic CMV effects were not found in both lavaged segments. In one of eight patients, mycobacteria could be cultured only from one of two radiologically involved segments. CONCLUSION: An increase in the diagnostic sensitivity by performing BAL in two lung segments is limited to cases where P carinii pneumonia is a relevant consideration in immunocompromised patients without HIV infection. In bacterial pneumonia, BAL can be performed in a single radiographically involved lung segment without a loss in diagnostic sensitivity. Since our study population of patients with CMV pneumonitis, mycobacterial infections, and fungal infections was small, no reliable conclusions are possible and BAL of more than one lung segment seems justified until more information is available. PMID- 7774314 TI - Respiratory care practitioners' attitudes toward patients with AIDS. AB - OBJECTIVE: To assess attitudes of respiratory care practitioners about AIDS and patients with AIDS. DESIGN: A questionnaire that explored attitudes about AIDS was disseminated throughout southern New Jersey. Identity of individual responders was protected carefully. RESULTS: One hundred fifty-nine responses were received. The majority of responders favored identification of patients with AIDS, segregation of those patients into AIDS wards, and then avoidance of the AIDS wards. There was some bias against patients with known high-risk behaviors (especially drug abuse), but once a patient had AIDS the fear of getting AIDS was the only factor that correlated (p = 0.001) with the desire to avoid AIDS patients. Thirty-nine percent of responders said that they used universal precautions less than 90 percent of the time, and no factor (including fear of AIDS and markers of education) predicted which therapists did not consistently use them. CONCLUSIONS: The desire to avoid AIDS represents a rational desire not to become infected with the HIV virus. This study documents an identify-and-avoid philosophy in lieu of careful use of universal precautions. Educational efforts need to emphasize that the use of precautions represents the only truly effective means of preventing infection with the AIDS virus and other communicable diseases. PMID- 7774313 TI - Bronchodilator pretreatment improves aerosol deposition uniformity in HIV positive patients who cough while inhaling aerosolized pentamidine. AB - OBJECTIVE: To determine the effect of bronchodilator pretreatment on deposition uniformity of aerosolized pentamidine (AP) in HIV-positive patients who coughed while inhaling AP. DESIGN: Nonrandomized control trial. SETTING: A university hospital. PATIENTS: Ten HIV-positive patients who were using AP prophylactically. INTERVENTION: Four patients who coughed during AP administration were pretreated with 10 mg metaproterenol aerosol prior to a second inhalation of AP. MEASUREMENTS: Skew, a measure of overall deposition symmetry, deposition in the apex vs the base of the right lung (A:B ratio), and percentage of change from baseline in peak expiratory flow rate (PEFR). RESULTS: At baseline, the average (+/- SD) skew value for four subjects who coughed (0.89 +/- 0.19) was significantly higher than for six control subjects (0.58 +/- 0.07) (p < 0.01), indicating enhanced nonuniformity of AP distribution. After bronchodilator, no one coughed and the average skew value was normalized to 0.57 +/- 0.13. The A:B ratios at baseline and after metaproterenol were not significantly different, suggesting that deposition of AP in the apex, relative to basal deposition, was not enhanced by bronchodilator treatment. When no bronchodilator was administered, average PEFR decreased to 330 +/- 162 from baseline (410 +/- 84). Average PEFR increased to 429 +/- 85 from baseline (395 +/- 116) after bronchodilator pretreatment. CONCLUSIONS: These results suggest that in addition to relieving cough in patients receiving AP prophylactically, pretreatment with metaproterenol enhances uniformity of distribution of AP and improves PEFR. PMID- 7774315 TI - Preventive therapy for contacts of multidrug-resistant tuberculosis. A Delphi survey. AB - OBJECTIVE: Several outbreaks of multidrug resistant tuberculosis (MDR-TB) have recently occurred in which healthcare workers and others have become infected. Given the lack of clinical data to guide preventive therapy for such contacts, a Delphi survey of a panel of 31 TB therapy experts was undertaken to identify a consensus regimen. DESIGN: An initial questionnaire presented three scenarios describing persons with significant exposure to MDR-TB and with new tuberculin skin test reactions > 15 mm (except one anergic patient) without evidence of disease. Panelists were asked to suggest possible preventive therapy regimens. METHODS: During a second round survey, the panel members were asked to review the suggested regimens provided for each scenario and to rank them from one to nine as extremely inappropriate to extremely appropriate. Results of this second survey were tabulated and shared with the members of the panel who were then asked to rerank each regimen in light of the previous cumulative panel responses. RESULTS: No specific regimen achieved initial positive consensus by predefined criteria. In two of the three scenarios the no treatment option, however, was deemed clearly inappropriate. The data were also analyzed by what percentage of respondents who ranked a regimen as at all appropriate (ie, six or more on the nine point scale). For scenarios involving a nurse, an HIV-positive tuberculin reactor, and a patient who was anergic HIV-positive, treatment with pyrazinamide 1,500 mg daily with ciprofloxacin 750 mg twice a day for 4 months received a somewhat appropriate rating from more than 50 percent of respondents. CONCLUSIONS: The management of persons exposed to and infected by patients with MDR-TB has become a serious problem in the context of MDR-TB outbreaks. This panel of experts agreed that some form of preventive therapy was warranted; however, they were not able to reach defined consensus on what regimen should be used, although a regimen of pyrazinamide 1,500 mg daily with ciprofloxacin 750 mg twice a day for 4 months was considered somewhat appropriate. Clinical data on the efficacy of alternative preventive therapy regimens for such contacts are urgently needed. PMID- 7774316 TI - Mycobacterial infection in renal transplant recipients. AB - STUDY OBJECTIVE: To determine the prevalence and presentation of mycobacterial infection as well as the influence on outcome in graft function and patient survival in renal transplant recipients at our institution. DESIGN: A retrospective review of case records of all renal transplant recipients from 1980 to 1992. SETTING: Groote Schuur Hospital, a large teaching hospital and regional tertiary referral center in Cape Town, South Africa. PATIENTS: During the period reviewed, 857 transplants were performed. The records of 487 patients who had remained in Cape Town were examined. RESULTS: There were 22 cases of mycobacterial infection (21 confirmed or presumed Mycobacterium tuberculosis and 1 unidentified Mycobacterium other than tuberculosis). In seven cases, immunosuppression had been intensified within 3 months of diagnosis. The median time from transplantation to diagnosis was 14 months (range, 2 to 74). Chest radiograph findings included consolidation (14), miliary pattern (4), pleural effusion (3), tuberculoma (2), cavitation (2), and hilar lymphadenopathy (1). Diagnosis of tuberculosis was made on sputum smears (eight), pleural biopsy specimen (two), fine-needle aspiration (one), and fiberoptic bronchoscopy in ten cases (brushings, eight; transbronchial biopsy specimen, three). Extrapulmonary tuberculosis (in addition to pulmonary tuberculosis) occurred in five patients (tuberculous meningitis, one; renal tuberculosis, one; and dissemminated infection, four). Five of the seven patients in whom immunosuppression had been intensified had concurrent infections; two of these died and the remainder returned to dialysis within 6 months. All but one patient received three antituberculosis drugs, including rifampin and isoniazid, for between 6 and 18 months. At the end of the period of review, 12 (59 percent) patients were alive, 10 with functioning grafts and 2 receiving dialysis. Four patients died while receiving antituberculosis treatment, but death was only directly related to tuberculosis in one case. CONCLUSIONS: Tuberculosis is an important infection in renal transplant recipients in Cape Town, but disseminated disease is less common than reported elsewhere. PMID- 7774317 TI - Reduction of environmental tobacco smoke exposure among asthmatic children: a controlled trial. AB - STUDY OBJECTIVE: This randomized clinical trial tested a behavioral medicine program designed to reduce asthmatic children's exposure to environmental tobacco smoke (ETS) in the home. DESIGN: Families were randomly assigned to an experimental preventive medicine counseling group, a monitoring control group, or a usual treatment control group. Families were measured six times over 1 year. PARTICIPANTS: Ninety-one families were recruited from four allergy clinics. INTERVENTION: The experimental group received a 6-month series of counseling sessions designed to decrease ETS exposure. This group also monitored smoking, exposure, and children's asthma symptoms. The monitoring group did not receive counseling and the usual treatment control group received outcome measures only. MEASUREMENTS AND RESULTS: Parents reported the daily number of cigarettes children were exposed to during the week preceding interviews. A nicotine air monitor and construct validity analysis confirmed the validity of exposure reports. Exposure to the parent's cigarettes in the home decreased for all groups. The experimental group attained a 79 percent decrease in children's ETS exposure, compared with 42 percent for the monitoring control and 34 percent for the usual treatment control group. Repeated-measures analysis of variance resulted in a significant (F([10,350] = 1.92, p < 0.05) group by time effect. At the final 12-month visit, the experimental/counseling group sustained a 51% decrease in children's exposure to cigarettes in the home from all smokers, while the monitoring control group showed an 18% decrease and the usual treatment control group a 15% decrease from pre-intervention [corrected]. CONCLUSION: A behavioral medicine program was successful in reducing exposure to ETS in the home for these asthmatic children. PMID- 7774318 TI - Demographic influences on asthma hospital admission rates in New York City. AB - Surveillance reports describe an increase in asthma prevalence, and cite New York City as an area of excessive asthma mortality. To assess trends and the influence of geography, race, and ethnicity on hospital admission rates for asthma between 1989 and 1991, data of all admissions for asthma to New York City hospitals were reviewed. The average citywide annual hospital admission rate was 681 per 100,000 population, and the racial and ethnic distribution was 1,003 per 100,000 Hispanic patients, 810 per 100,000 for blacks, and 242 per 100,000 for whites (p < 0.0001). Bronx and Manhattan had the highest admissions rates, and contained a few zip codes with very high rates. In these zip codes, admission rates were consistently highest among Hispanics, followed by blacks and whites. New York City asthma admission rates increased 12.7 percent during the study. Very high admission rates among Hispanic patients and high rates in blacks, in specific geographic areas, are responsible for this trend. Targeted education and treatment programs could reduce hospital admissions and mortality in small geographic areas with high asthma morbidity. PMID- 7774319 TI - Association between reported use of inhaled triamcinolone and differential short term responses to aerosolized albuterol in asthmatics in an emergency department setting. AB - Forty-four adult patients with acute asthma were treated with albuterol at a rate of 15 mg/h over 2 h. Analysis of covariance showed a significantly higher baseline adjusted mean for both percent predicted forced expiratory volume in 1 s (PFEV1) (p = 0.045) and percent predicted forced vital capacity (PFVC) (p = 0.022) at 50 and 110 min for the patients who reported triamcinolone use. Although heart rates decreased overall during the first hour of albuterol treatment, a rise in mean heart rate occurred during the second hour of treatment only in patients reporting triamcinolone use (p = 0.005). After accounting for the effects of parenteral corticosteroids, the effect of reported triamcinolone use remained significant. These data suggest that use of inhaled corticosteroids in this context may be associated with enhanced local and systemic beta responsiveness, and if a causal relationship could be confirmed, this may constitute yet another advantage of early inhaled corticosteroid treatment in asthma. These data also suggest that chronotropic effects of high-dose albuterol should be monitored in patients using inhaled triamcinolone. PMID- 7774320 TI - Roxithromycin reduces the degree of bronchial hyperresponsiveness in children with asthma. AB - We evaluated the effects of a new semisynthetic macrolide antibiotic, roxithromycin, on the bronchial hyperresponsiveness to histamine in children with asthma. Twelve hospitalized asthmatic children, aged 11 to 15 years (mean age, 12.9 years), were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. The PC20 value 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05, p < 0.01, respectively). No significant change was observed in serum theophylline concentrations during this study. Serum cortisol level in the morning did not change after the administration of roxithromycin for 4 weeks. These results suggest that administration of roxithromycin may act favorably in the treatment of childhood asthma. PMID- 7774321 TI - Reduction in patient timing errors using a breath-activated metered dose inhaler. AB - Delivery of aerosol medication to the lower respiratory tract by metered dose inhaler (MDI) is often limited by the patient's inability to properly coordinate activation of the device with inspiration. This study evaluated a new breath activated MDI device, designed to minimize patient timing errors by sensing inspiratory flow and automatically activating to deliver aerosol medication. Twenty novice adult volunteers, previously naive to the technique of MDI use, and 20 patients currently using MDIs were tested in their ability to coordinate MDI usage. Simultaneous recording of respiratory events and device activation allowed analysis of timing errors. With a conventional MDI, a 31.0 percent incidence of errors was seen in the novice group and a 21.5 percent incidence of errors was seen in the experienced group. These compared with error rates using the breath activated MDI of 6.5 percent and 5.0 percent in the two groups respectively (p = 0.009, p = 0.04). The breath-activated inhaler was preferred by 35 of 40 subjects. In conclusion, MDI technique timing errors were significantly less with this breath-activated MDI device in both novice and experienced subjects, and it was also preferred by both groups. PMID- 7774322 TI - Cardiac arrhythmias, snoring, and sleep apnea. AB - We investigated the frequency of cardiac arrhythmias in patients suspected of having sleep apnea, and related them to the severity of apnea, snoring, and nocturnal hypoxemia. We prospectively studied 458 patients who had nocturnal polysomnography which included objective measurement of snoring (quantified by the number of snores per hour of sleep [snoring index (SI)] and maximum nocturnal sound intensity [(dBmax)], as well as examination of the electrocardiogram (modified lead 2). We found 58 percent prevalence of arrhythmias in patients with sleep apnea (apnea/hypopnea index = AHI > 10), vs 42 percent in nonapneic controls (chi 2 = 16.7, p < 0.0001). Patients with arrhythmias had more severe apnea and nocturnal hypoxemia, but not snoring, than patients without arrhythmias. To examine separately the relationship between the prevalence of arrhythmias and snoring, nocturnal oxygenation, and apnea--we selected subgroups of patients "at the opposite ends of the spectrum" with respect to the severity of snoring, hypoxemia, and apnea. We found that 38 percent of light snorers had arrhythmias vs 39 percent of heavy snorers, 82 percent of patients with mean nocturnal oxygen saturation < 90 percent had arrhythmias vs 40 percent of patients with mean nocturnal oxygen saturation > 90 percent (chi 2 = 7.4, p = 0.006), and 70 percent of patients with AHI > or = 40 had arrhythmias vs 42 percent with AHI < or = (chi 2 = 9.2, p = 0.002). We conclude that patients with sleep apnea as a group have higher prevalence of cardiac arrhythmias than nonapneic patients and that snoring alone, without concomitant sleep apnea, is not associated with increased frequency of cardiac arrhythmias. PMID- 7774323 TI - Accuracy of end-tidal and transcutaneous PCO2 monitoring during sleep. AB - STUDY OBJECTIVE: Although it is intuitively desirable, the measurement of arterial carbon dioxide tension (PaCO2) during diagnostic polysomnography and nocturnal trials of positive pressure therapy is invasive and potentially expensive. The accuracy of end-tidal carbon dioxide tension (PETCO2) and transcutaneous carbon dioxide (tcPCO2) monitoring in these contexts has not been systematically evaluated. This investigation was undertaken to evaluate the accuracy of PETCO2 and tcPCO2 in patients undergoing polysomnography. METHODS AND PROCEDURES: Values of PETCO2 were compared with PaCO2 in 19 patients spontaneously breathing room air (condition 1), in 13 patients receiving supplemental oxygen via nasal cannula (condition 2), and in 22 patients receiving nocturnal positive pressure ventilatory assistance (all but one with continuous positive airway pressure or bilevel positive airway pressure) (condition 3). The accuracy of tcPCO2 monitoring during sleep was also examined by comparing tcPCO2 values with simultaneously recorded PaCO2 values obtained during sleep in patients undergoing nocturnal polysomnography. Data were collected using three commercially available brands of tcPCO2 monitors (capnograph R, n = 17 patients; capnograph S, n = 17; and capnograph N, n = 15). RESULTS: Accuracy of PETCO2- There was significant scatter in the PaCO2 vs PETCO2 relationship such that only 23 percent of the variability in PaCO2 was explained by variation of PETCO2 during condition 1 and only 15 percent and 20 percent of the variability in PaCO2 was explained by variation of PETCO2 during conditions 2 and 3, respectively. 21.3 percent of patients had average PETCO2 values in error by > 10 mm Hg during condition 1, while during conditions 2 and 3, 46.2 and 63.7 percent of patients had average values in error by > 10 mm Hg, respectively. Accuracy of tcPCO2- While capnographs S and N generally overestimated PaCO2 with a wide scatter, capnograph R tended to have offsetting overestimations and underestimations of PaCO2 with a wide scatter. With each capnograph, a relatively small portion of the variability of the PaCO2 was explained by variability of the tcPCO2 (r2 = 0.2, 0.45 and 0.64 for capnographs S, N, and R, respectively). Across the three capnographs, 43.1 to 66.7 percent of measurements were in error by > 10 mm Hg, and 5 to 20 percent of measurements reflected errors > 20 mm Hg. There was no consistent relationship between the tcPCO2 error and the level of PaCO2, nor was the tcPCO2 error consistent in individual patients. There was no relationship between tcPCO2 accuracy and body mass index. CONCLUSION: Neither PETCO2, measured within a face mask, nor tcPCO2 is a consistently accurate reflection of PaCO2. This limits the utility of these variables in monitoring patients during diagnostic and therapeutic sleep studies, and in particular, during trials of nocturnal ventilatory assistance where adequate levels of support are to be established and unacceptable hyperventilation and respiratory alkalosis must be recognized. PMID- 7774324 TI - The radiographic findings of fibrosing mediastinitis. AB - We retrospectively reviewed the radiographic findings of fibrosing mediastinitis (FM) in 33 patients. Imaging studies included chest radiographs, computed tomographic scans, magnetic resonance imaging examinations, esophograms, ventilation perfusion scans, angiograms, and venograms. Findings include bronchial narrowing in 11 patients (33 percent), pulmonary artery obstruction/narrowing in 6 patients (18 percent), esophageal narrowing in 3 patients (9 percent), and superior vena cava obstruction/narrowing in 13 patients (39 percent). Two distinctly different radiographic patterns were identified: a localized pattern seen in 27 patients (82 percent) that frequently contained calcification and a diffuse pattern seen in 6 patients (18 percent) that did not contain calcification. The localized pattern is most likely due to histoplasmosis and does not show radiographic evidence of improvement with steroid therapy. The diffuse pattern may more likely be truly idiopathic or of a noninfectious etiology. Several patients with the diffuse pattern showed radiographic evidence of improvement with steroid therapy. PMID- 7774325 TI - Radiologic findings of adult primary immunodeficiency disorders. Contribution of CT. AB - STUDY OBJECTIVE: We wished to review the chest radiographic and computed tomographic (CT) findings in adults with primary immunodeficiency disorders, and to evaluate the influence of CT on the treatment of these patients. DESIGN: Retrospective blinded review of radiographs, CT scans, and clinical data. SETTING: National referral center for immunodeficiency disorders. PATIENTS: Forty six chest radiographs and 22 CT examinations of subjects with primary immunodeficiency disorders were independently scored. Nineteen of the subjects who had CT scans had B-cell deficiency, while 3 had T-cell deficiency. RESULTS: CT-detected bronchiectasis in 15 of 19 subjects with B-cell deficiency, compared with 7 cases detected on chest radiograph. Unsuspected upper lobe bronchiectasis was found on CT in 15 cases. Other CT findings in this group included small nodules in seven subjects, interstitial lines in four, air trapping in seven, ground glass or parenchymal consolidation in nine, evidence of small airways disease in nine, and mucus plugs in four. Two of the three subjects with T-cell disorders showed cavitation and two had unsuspected reactive mediastinal adenopathy. Clinical management appeared to be altered in five subjects with B cell deficiency by CT findings of severe focal or diffuse bronchiectasis or small airways disease. Additionally, CT localized the bleeding site in three subjects with hemoptysis. CONCLUSIONS: CT is valuable for detection of bronchiectasis in subjects with B-cell immunodeficiency and may alter treatment of these patients. PMID- 7774326 TI - Chemoprevention effects on bronchial squamous metaplasia by folate and vitamin B12 in heavy smokers. AB - The purpose of this study was to observe the effects of folate and vitamin B12 on bronchial squamous metaplasia with cellular atypia, known to be a precancerous change, in heavy smokers. Cases of squamous metaplasia were recognized on sputum cytologic study. The location of bronchial lesions was identified by bronchofiberoscopy in all cases. The grade of cellular atypia was evaluated on the basis of histologic specimens. Thirty-eight patients with squamous metaplasia, including 21 patients receiving folate and vitamin B12 and 17 patients without any medication, were investigated prospectively for 1 year. Consecutive bronchofiberoscopic examinations were performed in each patient in 3 to 4 months after the first examination in order to evaluate the lesions. Grades of cellular atypia were examined by histologic specimens using a scoring system from 0 to 3. There was no significant difference in mean scores at entry in the medication group (1.7) and control group (1.4). The medication group showed significant decrease in mean scores (0.4) while the control group had no change in mean scores (1.2) at termination. Plasma levels in the medication group were significantly increased at termination of the study while those of the control group showed a slight decrease. The results show that the cellular atypia squamous metaplasia in heavy smokers can be reduced by administration of folate and vitamin B12. PMID- 7774327 TI - Persistent respiratory health effects after a metam sodium pesticide spill. AB - STUDY OBJECTIVE: To report the occurrence of persistent respiratory disorders, including irritant-induced asthma, among adults living and working near an environmental spill of the pesticide, metam sodium, after the derailment of a tank car. DESIGN: Retrospective clinical case series. SETTING: California communities situated within one-half mile of the Sacramento River, from Mt. Shasta City to Shasta Lake. PATIENTS: 197 adults referred to a university occupational/environmental health clinic or to a private occupational/environmental health practitioner for evaluation of health problems potentially related to the spill. MEASUREMENTS AND RESULTS: History, physical examination, review of medical records, spirometry, and methacholine challenge testing revealed 20 cases of persistent irritant-induced asthma and 10 cases of persistent exacerbation of asthma. CONCLUSIONS: This is the first reported series of cases of persistent irritant-induced asthma involving both community residents and occupationally exposed individuals. PMID- 7774328 TI - Mortality due to farmer's lung in Finland. AB - Fatal cases of farmer's lung (FL) are rare. We found, based on death certificates, 13 cases of FL with a fatal outcome in Finland between 1980 and 1990. Compared with incidence data from the years 1980 to 1982, the mortality was estimated as 0.7 percent. On average, death occurred 8 years after the diagnosis of FL. One patient died acutely after a heavy mold exposure. The other patients had chronic disease. Among them the immediate cause of death was pneumonia in seven patients, respiratory insufficiency in four, and pneumothorax in one patient. The majority of these patients with a fatal outcome had suffered from symptoms of FL for more than 1 year before the diagnosis was established and fibrotic changes were already visible in the chest radiograph at the time of the diagnosis. PMID- 7774329 TI - Immune responses to Aspergillus fumigatus and Pseudomonas aeruginosa antigens in cystic fibrosis and allergic bronchopulmonary aspergillosis. AB - Allergic bronchopulmonary aspergillosis (ABPA) in Cystic Fibrosis (CF) is well documented. Aspergillus fumigatus is the causative agent of ABPA, and Pseudomonas aeruginosa particularly the mucoid variety has been frequently isolated from the sputum of patients with CF. This study investigates the cellular and humoral immune response to both A fumigatus and P aeruginosa antigens in patients with CF and ABPA (CF/ABPA), CF only, and healthy controls. The A fumigatus and P aeruginosa antigen specific IgE and IgG in sera and peripheral blood mononuclear cell culture supernatants (PBMC sups), lymphoproliferation to antigens, and leukotriene B4 (LTB4) were measured. Results indicate significant elevated levels of A fumigatus specific IgG (A fumigatus-IgG) and Paeruginosa-IgE in serum. Significant Paeruginosa-IgG was measured in PBMC sups. The concanavalin A nonbinding A fumigatus antigen, previously shown to induce specific T-cell responses in vitro in patients with ABPA, elicited significant lymphoproliferative response in a greater proportion of patients with CF/ABPA and not in CF or controls, underlining the importance of this antigen in the diagnosis of ABPA. In contrast, a greater proportion of the CF group responded to P aeruginosa antigens compared with the controls and CF/ABPA. Hence, the CF and CF/ABPA groups respond to both P aeruginosa and A fumigatus antigens with the former group responding strongly to P aeruginosa and the latter to A fumigatus antigens. PMID- 7774330 TI - A simplified insertion technique for tracheobronchial silicone stents. AB - In many patients with central airway obstruction due to extrinsic compression or malacia, insertion of tracheobronchial stents can provide effective and permanent relief. Of the various types of prostheses described, the silicone Dumon-Artemis stents (Medicore, Brussels, Belgium) are probably the most efficient. The use of an elegant and safe specially designed stent introducer system combined with a special bronchoscope is proposed for insertion by Dumon. This combined stent insertion system, however, is relatively expensive and cumbersome, especially for centers where relatively limited numbers of patients are treated. We propose an alternative, simplified insertion technique of silicone Dumon-Artemis stents, which was proven safe and efficient in our series of patients. PMID- 7774331 TI - Quality of life after cardiopulmonary resuscitation. AB - OBJECTIVES: This study evaluates the influence of Cardiopulmonary Resuscitation (CPR) on the components of quality of life (QOL) of patients after discharge from the hospital. DESIGN: Extracted from a prospective national survey on Dutch intensive care units (ICUs). SETTING: Thirty-six ICUs of both university and nonuniversity hospitals, spread throughout the country. METHODS: For a period of 6 months, 9,803 consecutive ICU admissions entered the study. Outcome in connection with in-hospital CPR was analyzed by comparing the CPR group (n = 477) with a standardized control group without CPR (n = 500). INTERVENTIONS: Activities of daily living were registered at the time of hospital admission. A record was kept of each patient for demographics, severity of illness, length of stay, daily use of manpower and ICU technology, and mortality. Six months after hospital discharge, the QOL of 69 patients in both the CPR and control groups was measured with the Sickness Impact Profile (SIP). RESULTS: CPR was performed in 4.8 percent of the patients, mainly from the general ward. These patients were older, had a higher severity of illness, and a higher daily consumption of nursing resources. The QOL did not correlate with severity of illness on admission, length of stay, or consumption of resources in the ICU. On the whole, the SIP scores of both CPR and control groups did not differ much: 11.7 vs 10.7, and circulatory arrest did not appear to impair the self-sufficiency in the study group significantly in comparison with the controls. An increased dysfunction was found in the CPR group of patients concerning their work and their psychosocial functioning. CONCLUSION: Patients who have recovered from a circulatory arrest after CPR resuscitation find their capacity for resuming work diminished after discharge from the hospital, while they seem to experience a postponed negative effect on their mental functioning, especially the functions connected with the awareness of their environment. PMID- 7774332 TI - Tracheal aspirate correlates with protected specimen brush in long-term ventilated patients who have clinical pneumonia. AB - STUDY OBJECTIVE: This study was undertaken to determine whether tracheal aspirate cultures correlate with protected specimen brush (PSB) cultures in the diagnosis of probable ventilator-associated pneumonia (VAP). DESIGN: Retrospective evaluation of 52 episodes of clinical pneumonia in 38 patients who underwent bronchoscopy and PSB as well as tracheal aspirate cultures. SETTING: The study took place in long-term, acute care hospital associated with a university medical school. This hospital specializes in ventilator-assisted patients. PATIENTS: The patient population consisted of long-term ventilated patients (average ventilation time was 22 weeks; range, 4 weeks to 3 years) who presented with the clinical diagnosis of VAP (fever, increased white blood cell count, new infiltrate on chest radiograph, and bronchorrhea). No patient had received antibiotics for the preceding 5 days at the time of bronchoscopy or tracheal aspirate culture. MEASUREMENTS: The tracheal aspirate and PSB culture and sensitivities results. RESULTS: Identical organisms were recovered in both the tracheal aspirate and PSB cultures in 36 of 52 episodes of VAP (69 percent). No organism was recovered in either the tracheal aspirate or the PSB in 4 of 52 suspected episodes (8 percent). Positive bacterial cultures in the tracheal aspirate but not the PSB were found in 8 of 52 (15 percent) episodes. In 3 of 52 episodes (6 percent), 1 isolate of pathogenic bacteria was found on PSB and 2 were found on tracheal aspirate cultures. However, all three isolates had the similar antibiotic sensitivities. In the final episode, the PSB culture grew an organism that was not present in the tracheal aspirate culture (2 percent). When comparing the tracheal aspirate with the PSB, the following were calculated: sensitivity = 97.7 percent; specificity = 50 percent; positive predictive value = 91.3 percent; and negative predictive value = 80 percent. CONCLUSION: Tracheal aspirate cultures correlate with PSB cultures in patients receiving long-term ventilation who have clinical pneumonia, and they can be used to direct initial antibiotic therapy in this group of patients. PMID- 7774333 TI - Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history. AB - STUDY OBJECTIVE: To establish the natural history of lung injury in adult respiratory distress syndrome (ARDS) in terms of increased pulmonary vascular permeability. Secondly, to relate such changes to the number of neutrophils in bronchoalveolar lavage (BAL) and a clinical score of the severity of lung injury. DESIGN: Prospective, open. SETTING: Adult intensive care unit of a tertiary (national) referral hospital. PATIENTS: Fourteen patients meeting accepted diagnostic criteria for ARDS. INTERVENTIONS: Mechanical ventilatory support. Conventional intensive care and support for other failed organ systems as appropriate. MEASUREMENTS AND RESULTS: Pulmonary vascular permeability was estimated using a dual isotope technique (protein accumulation index [PAI]), neutrophil numbers by BAL and the severity of ARDS by the lung injury score (LIS). The PAI and LIS were measured simultaneously on three occasions as far apart as possible during the course of the illness. A single BAL was performed immediately after one of the three PAI/LIS measurements, the precise timing being dictated by the clinical stability of each patient. Fourteen patients (8 male; age range, 19 to 69 years) were studied, 1.40 +/- 0.16, 11.36 +/- 1.79, and 20.90 +/- 2.30 days after the onset of ARDS (mean +/- SEM). Six patients died. The PAI (normal range, 0 to 1.0 x 10(-3)) was 2.81 +/- 0.39, 2.94 +/- 0.48, and 2.80 +/- 0.87; and LIS (severe injury > or = 2.5) was 2.18 +/- 0.25, 2.48 +/- 0.14, and 2.06 +/- 0.27, respectively. The BAL neutrophil content was 54.09 +/- 8.89. There were significant positive correlations between PAI and LIS (r = 0.73, p < 0.001) and PAI and BAL neutrophil content (r = 0.81, p < 0.001). CONCLUSIONS: These data suggest that increased pulmonary vascular permeability persists throughout the course of ARDS and is related to a clinical score of injury severity and BAL neutrophil content. PMID- 7774334 TI - Comparison of pressure and flow triggering systems during continuous positive airway pressure. AB - STUDY OBJECTIVE: Compare the inspiratory work of breathing (WOBI) during pressure triggering (PT), and flow triggering (FT) using two microprocessor ventilators. DESIGN: A randomized, crossover comparison of triggering strategies and ventilators used. SETTING: Surgical intensive care unit. PATIENTS: Ten patients recovering from acute respiratory failure (eight men, two women; mean age, 48 +/- 12 years) breathing on continuous positive airway pressure (CPAP) of 5 cm H2O were studied. INTERVENTIONS: Patients were randomly assigned to either receive 5 cm H2O CPAP via one of two units (Hamilton Veolar or Puritan Bennett 7200ae) using either PT or FT. Each patient had 30-min trials using the following: (1) Veolar FT; (2) Veolar PT; (3) 7200ae FT; and (4) 7200ae FT. MEASUREMENTS AND RESULTS: During each trial period, work of breathing (WOB) and pressure time product (PTP) were measured using a respiratory monitor (Bi-core CP-100). All patients were placed in semi-Fowler position and esophageal balloons were inserted and their position confirmed using the occlusion technique. Continuous measurements of peak negative pressure during inspiration, tidal volume (VT), minute ventilation (VE), respiratory frequency (f) were accomplished with a flow transducer at the proximal airway. FT with the 7200ae was superior to PT as measured by both the WOB (0.58 +/- 0.3 vs 0.84 +/- 0.2 J/L, p < 0.01) and PTP (148 +/- 50 vs 206 +/- 41 cm H2O/s/min, p, 0.05). FT with the Veolar was also superior to PT with respect to the WOB (0.53 +/- 0.2 vs 0.93 +/- 0.2 J/L, p < 0.01) and PTP (140 +/- 39 vs 229 +/- 46 cm H2O/s/min, p < 0.05). CONCLUSION: FT reduces the WOB compared with PT, regardless of the ventilator used. The reduction in WOB during FT is related to improved responsiveness and changes in the posttrigger phase. PMID- 7774335 TI - Portable chest radiographs identify mechanical ventilator-associated hyperinflation. AB - OBJECTIVE: Portable chest radiographs (CRs) are obtained routinely in mechanically ventilated patients, but little is known about relationships between CR findings and ventilator parameters. It is unclear whether radiographically apparent hyperinflation correlates with tidal volume (VT), body weight (BW), VT/kg, or levels of peak airway pressure (PAP), positive end-expiratory pressure (PEEP), or pressure support (PS). DESIGN: Prospective comparison of CR and ventilator parameters in 62 mechanically ventilated patients in surgical and medical intensive care units of a university hospital. PATIENT SELECTION: All mechanically ventilated adults with portable CR on four separate dates. METHODS: Chest radiographs were classified by subjective assessments as hyperinflated (H+) or nonhyperinflated (H-), independent of knowledge of patients or their mechanical ventilation. Chest radiographs were reclassified independently as H+, H-, or indeterminate by a radiologist using objective criteria. Ventilator parameters recorded at the time of the CR were obtained and compared. RESULTS: Patients with CRs classified subjectively as H+ compared with patients with CRs classified as H- had a larger VT/kg (12.0 +/- 0.4 ml/kg [mean +/- SEM] vs 10.2 +/ 0.4; p = 0.004), lower BW (70.8 +/- 2.9 kg vs 81.5 +/- 3.8; p = 0.03), higher PEEP (6.5 +/- 0.5 cm H2O vs 5.0 +/- 0.4; p = 0.01), and higher PAP (38.2 +/- 2.1 cm H2O vs. 33.4 +/- 1.8; p = 0.06). Using objective CR classifications, patients with H+ CRs had a VT/kg of 12.6 +/- 0.4, larger than in the indeterminate (11.1 +/- 0.8) and H- (9.9 +/- 0.3) groups (p < 0.001). The BW differed among objectively classified groups (66.5 +/- 2.7 H+, 68.9 +/- 5.1 indeterminate, and 85.2 +/- 3.7 H-; p < 0.001), but other ventilator parameters did not correlate univariately with the degree of inflation on CR. Multivariate analysis showed that higher VT was predictive of H+ after adjusting for BW in subjective (p = 0.076) and objective (p = 0.017) classifications. PEEP (p = 0.004) and older age (p = 0.021) were also associated with H+ in multivariate analysis. Four of 25 (16 percent) patients with objectively H+ CRs developed barotrauma, while no patient with H- CR had this complication (p = 0.037). CONCLUSIONS: In mechanically ventilated patients, hyperinflation seen on portable CR is associated with higher VT, VT/kg, and lower BW, and may help predict subsequent barotrauma. PMID- 7774336 TI - Regular beta-adrenergic agonists. Evidence, not reassurance, is what is needed. PMID- 7774337 TI - Administration of therapeutic aerosols to mechanically ventilated patients. PMID- 7774338 TI - An asymptomatic pleural mass in a 72-year-old man. PMID- 7774339 TI - Sternal mass. PMID- 7774340 TI - Comparison of the effectiveness of tetracycline and minocycline as pleural sclerosing agents in rabbits. AB - Parenteral tetracycline, one of the most commonly used agents for producing pleurodesis, is no longer available because of stricter regulations governing the manufacturing process. The objective of this project was to determine whether minocycline, a tetracycline derivative, is an effective sclerosant in an experimental model in rabbits. We also studied the relationship of the dose and the volume injected to the degree of pleurodesis. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg; or minocycline, 4, 7, 10, or 20 mg/kg, diluted to a total volume of 1 or 2 ml of bacteriostatic saline solution; or minocycline, 40 mg/kg, diluted to a total volume of 2 ml of the solution. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis grossly and microscopically after the injection of 7, 10, 20, or 40 mg/kg of minocycline was comparable to that after the injection of 35 mg/kg of tetracycline, while the dose of 4 mg/kg was less effective. In the animals who received the higher doses of minocycline intrapleurally (ie > or = 20 mg/kg), there was an excess mortality both early (chi 2 = 3.61, 0.05 < p < 0.10) and late (chi 2 = 11.0, p < 0.005) which appeared to be related to the development of hemothorax. The intrapleural injection of the tetracycline derivatives was significantly (p < 0.05) more effective when the total volume of the solution was 2 ml rather than 1 ml. The present study demonstrates that minocycline is an effective agent for producing pleurodesis in the rabbit. Minocycline given intrapleurally at doses of 7 mg/kg or above is comparable to tetracycline, 35 mg/kg. Higher doses of minocycline (> or = 20 mg/kg) produce a high mortality that seems to be related to hemothorax. Since, in humans, a large experience confirms only 20 mg/kg of tetracycline is needed to produce adequate pleurodesis safely, we recommend a dose of 4 mg/kg of minocycline for the production of pleurodesis. PMID- 7774341 TI - Effect of intratracheal dexamethasone on oleic acid-induced lung injury in the rat. AB - The therapeutic efficacy of single-dose intratracheal dexamethasone (2.5 mg/kg) in oleic acid-induced acute lung injury in the rat was established by showing significant improvement in bronchoalveolar lavage parameters and lung compliance at 24 h after oleic acid as compared with animals not treated with oleic acid. An equivalent dose of intraperitoneal dexamethasone demonstrated no therapeutic benefit at 24 h after oleic acid. The therapeutic effect of this single-dose intratracheal dexamethasone regimen was accompanied by recovery to normal bronchoalveolar parameters and lung compliance at 7 days, in contrast to previous observations made with high-dose sustained intraperitoneal dexamethasone (4 mg/kg for 7 days). This improved benefit:toxicity ratio of intratracheal dexamethasone compared with systemic dexamethasone may be due to enhanced topical anti inflammatory potency relative to systemic potency and toxicity. PMID- 7774342 TI - Staging of bronchogenic carcinoma by bronchoscopy. PMID- 7774343 TI - Cardiovascular manifestations of cocaine abuse. A case of recurrent dilated cardiomyopathy. AB - The medical complications of cocaine abuse are being encountered by clinicians with increasing frequency. The cardiovascular manifestations of cocaine abuse include chest pain, myocardial ischemia and infarction, congestive heart failure, arrhythmias, infective endocarditis, and aortic dissection. The pathogenesis of these cardiovascular complications has not been fully elucidated but may be related to a combination of the sympathomimetic and membrane anaesthetic effects of cocaine. We present these concepts in a case discussion format. PMID- 7774344 TI - Brain abscess caused by Blastomyces dermatitidis in a child with cystic fibrosis. AB - An 8-year-old girl with moderately severe cystic fibrosis and right upper lobe bronchiectasis developed a cerebellar abscess caused by Blastomyces dermatitidis. To our knowledge, this is the youngest child with cystic fibrosis and a brain abscess, and the first documented case caused by a fungus. PMID- 7774345 TI - Hepatic vein obstruction due to Swan-Ganz catheter placement. AB - Complications from Swan-Ganz catheters during insertion, long-term placement, or removal have been known since its development. I describe the unusual presentation of a pacing Swan-Ganz catheter mispositioned into the hepatic vein producing vascular obstruction, yet with adequate cardiac pacing. PMID- 7774346 TI - Miliary mesothelioma. AB - Metastases in pleural mesothelioma usually occur late in the disease process. Diffuse involvement of the lung parenchyma is rare. A patient with miliary pulmonary parenchymal involvement with malignant mesothelioma is described. To our knowledge, this represents the first such case reported. PMID- 7774347 TI - Round atelectasis as a complication of Legionnella pneumonia. AB - Round atelectasis is a rare lung pseudotumor that is most commonly associated with asbestos-related pleural disease but can result from a variety of chronic pleural diseases. We describe a patient who developed round atelectasis over a period of only several months following an acute pleuropulmonary illness caused by Legionnella pneumophila. PMID- 7774348 TI - Mirror-image tumors in mirror-image twins. AB - Genetic factors are known to play a role in causing lung cancer. Twin cases of bronchioloalveolar, squamous, and anaplastic bronchogenic carcinoma have been previously reported. We describe mirror-image twins with adenocarcinoma of the lung occurring in mirror-image locations. They shared smoking and an occupational risk, carpentry, in addition to identical genetic backgrounds. PMID- 7774349 TI - Hemodynamic compromise secondary to a mediastinal bronchogenic cyst. AB - Bronchogenic cysts are not commonly the cause of severe symptoms, and often present only as an abnormality on chest roentgenogram. We report an unusual patient with a mediastinal bronchogenic cyst associated with rapid hemodynamic deterioration secondary to compression of vital structures. PMID- 7774350 TI - Interferon-related bronchiolitis obliterans organizing pneumonia. AB - We present an unusual case of a patient with chronic hepatitis C who experienced dyspnea, fever, and cough after 2 1/2 months' treatment with interferon. His radiograph demonstrated diffuse pulmonary infiltrates and bronchoalveolar lavage fluid showed an increase in lymphocytes, especially CD8-positive cells. The lung biopsy findings were bronchiolitis obliterans organizing pneumonia (BOOP). The pulmonary symptoms disappeared and the chest radiograph became normal after interferon therapy was discontinued and corticosteroid therapy was given. Interferon is suspected to be responsible for the BOOP. PMID- 7774351 TI - Thoracoscopic retrieval of a fractured thoracentesis catheter. AB - With the resurgence of laparoscopic surgical procedures, thorascopic procedures have followed close behind. Many procedures which in the past have required formal thoracotomy may now be performed via less invasive methods. Presented herein is a report and description of thoracoscopic retrieval of a fractured thoracentesis catheter. PMID- 7774352 TI - Abnormal movement of the arytenoid region during exercise presenting as exercise induced asthma in an adolescent athlete. AB - A 16-year-old female basketball player presented with a 2 1/2-year history of exercise-induced severe dyspnea, stridor, and mild wheezing that did not respond to prophylactic treatment with beta-agonists and cromolyn. Spirometric data at rest were normal, but flow-volume loops during exercise suggested a variable extrathoracic obstruction. Laryngoscopic evaluation while the patient was riding an exercise bicycle demonstrated an abnormal motion of the arytenoid region causing obstruction of the airway during inspiration. The vocal cords moved normally. This patient demonstrates the capacity of supraglottic tissue to obstruct the airway during exercise as a cause for exercise-induced dyspnea and stridor. Patients with this disorder may be misdiagnosed as having exercise induced asthma. PMID- 7774353 TI - Microneurographic evidence of sudden sympathetic withdrawal in carotid sinus syncope; treatment with ergotamine. AB - A proportion of patients with carotid sinus syncope (CSS) remain symptomatic even after pacemaker implantation because of persistence of a vasodepressor component. We report a patient with CSS whose syncopal episodes could be reproduced by carotid sinus massage and were due to profound hypotension associated with sudden sympathetic withdrawal, based on direct measurements of sympathetic nerve traffic. A double-blind trial with inhaled ergotamine provided significant symptomatic relief. PMID- 7774354 TI - Metastatic pulmonary calcification mimicking air-space disease. Technetium-99m MDP SPECT imaging. AB - Metastatic pulmonary calcification (MPC), a complication of chronic renal failure, is uncommonly diagnosed antemortem, yet may be a significant etiology of pulmonary dysfunction in patients with renal failure. The degree of respiratory distress often does not correlate with the degree of macroscopic calcification. Patients with extensive calcification may be asymptomatic, while others with subtle calcification or normal chest radiographs may have severe respiratory compromise. Additionally, the findings on chest radiographs may be confused with air-space disease, including pulmonary edema and pneumonia. Radionuclide imaging may detect MPC in the setting of normal chest radiographs, and confirm the diagnosis when there are radiographic findings of air-space disease without macroscopic calcification. We present a patient with bilateral upper lobe disease suspected to represent edema or pneumonia, proven to represent MPC on 99mTc MDP scintigraphy with single photon emission computed tomography (SPECT), CT, and later at transbronchial biopsy. PMID- 7774355 TI - Mediastinitis with fistula formation to the left main bronchus. A complication of wisdom tooth extraction. AB - We describe a 23-year-old patient who after extraction of four wisdom teeth developed a descending necrotizing mediastinitis with a spontaneous fistula to the left main bronchus. Because of this fistula, treatment was limited to surgical drainage of the neck region and antibiotics. Recovery was uneventful. PMID- 7774356 TI - Rupture of thoracic aorta caused by penetrating aortic ulcer. AB - We present the findings in a 57-year-old man with a rupture of the thoracic aorta that originated in a penetrating atherosclerotic aortic ulcer. It formed a large hematoma that clinically mimicked a true saccular thoracic aneurysm. The possibility of penetrating aortic ulcer should be considered in the differential diagnosis of aortic aneurysm. PMID- 7774357 TI - Application of ultrafast computed tomography for diagnosis of perivalvular abscesses. Surgical implications. AB - The presence of a perivalvular abscess is associated with an increased risk of morbidity and mortality with valve replacement and can require extensive debridement and reconstructive procedures. An accurate noninvasive method for preoperative diagnosis may hasten operation and aid in preoperative and surgical management. Two cases are presented in which ultrafast computed tomography accurately identified perivalvular abscesses not detected on two-dimensional transthoracic echocardiography and guided operative intervention. PMID- 7774358 TI - In vivo diagnosis of pulmonary atherosclerosis. Role of intravascular ultrasound. AB - The application of intravascular ultrasound (IVUS) in diagnosing pulmonary artery atherosclerosis is described. To the best of our knowledge, this is the first description of the use of this technique in the recognition of pulmonary atherosclerosis. We describe a patient with long-standing primary pulmonary hypertension with evidence of pulmonary artery calcification seen on a chest x ray film. The IVUS imaging of the pulmonary arteries identified intimal disruption with complex atherosclerosis. Thus, IVUS can be a useful tool in the diagnosis of pulmonary artery atherosclerosis. PMID- 7774359 TI - Unusual presentation of gastric dilatation. Dramatic complete atrioventricular block. AB - We report a case of gastric dilatation in a ventilated 18-year-old woman, which was revealed by the acute onset of hypotension, sinus bradycardia, and complete atrioventricular block. Hypotension and cardiac rhythm disturbances resolved with intravenous injection of atropine, but recurred a few minutes later and required a second bolus of atropine, which had a transient beneficial effect. Only gastric decompression, as soon as gastric distention was recognized, was able to restore normal cardiac rhythm and adequate blood pressure. This case highlights the seriousness of gastric dilatation and argues for the vagal mechanism of cardiac rhythm and conduction troubles complicating gastric dilatation. PMID- 7774360 TI - Left pleural hemorrhagic effusion. A presenting sign of thoracic aortic dissecting aneurysm. AB - Left hemorrhagic pleural effusion was the presenting sign of painless aortic dissecting aneurysm in two elderly hypertensive patients. Computed tomography (CT) of the chest revealed the aneurysmal dilatation of the thoracic aorta and an intimal flap connecting its descending part with the left pleural space. The patients were treated conservatively with blood transfusions and drugs directed to control blood pressure. The first reported 71-year-old patient remains in stable condition for 16 months without evidence of recurrent active aortic dissection. The second 85-year-old patient remained in stable condition for 28 days, but finally had a second fatal episode of dissection into the left pleural space. The differential diagnosis of nontraumatic left hemorrhagic pleural effusion in an elderly hypertensive patient should include dissecting aneurysm of the descending thoracic aorta and CT of the chest should be performed as the next preferable diagnostic procedure. PMID- 7774361 TI - Childhood pulmonary alveolar proteinosis. Extracorporeal membrane oxygenation with total cardiopulmonary support during bronchopulmonary lavage. AB - Partial cardiopulmonary bypass with extracorporeal membrane oxygenation to allow bilateral bronchopulmonary lavage in pulmonary alveolar proteinosis has been described. However, this technique is complicated by a very low arterial PO2 and cardiovascular embarrassment. Total cardiopulmonary support avoids these problems and was successfully used in a 2 1/2-year-old girl. PMID- 7774362 TI - Bronchogenic carcinoma in patients seropositive for human immunodeficiency virus. AB - The purpose of this report is to describe an association between bronchogenic carcinoma and HIV. Three HIV-seropositive patients are described who developed bronchogenic cancer (two large cell, one adenocarcinoma) before developing an AIDS-defining illness. A critical review of the literature revealed 22 other patients in which the association of HIV infection and lung cancer is reported. These patients are characterized by a relatively young age at diagnosis (median, 43 years) and prevalence of the adenocarcinoma subtype (13 of 25 patients). Twenty of 21 patients had a history of smoking. Among 21 patients for whom data were available, 6 patients (28 percent) had AIDS at time of diagnosis of lung cancer while 11 patients (55 percent) did not have AIDS or AIDS-related complex at diagnosis. PMID- 7774363 TI - Performing thoracoscopy. The controversy continues. PMID- 7774364 TI - Mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. PMID- 7774365 TI - Diagnosis of Pneumocystis carinii infection in HIV-seropositive patients by identification of P carinii in pleural fluid. PMID- 7774366 TI - Crossreactivity of Candida with pneumocystis. PMID- 7774367 TI - The upper airway resistance syndrome. PMID- 7774368 TI - Ventilator-associated pneumonia. PMID- 7774369 TI - Providing a comfortable fitted mask. PMID- 7774370 TI - Pressure control ventilation. PMID- 7774371 TI - Asbestos-related pleural plaques and lung cancer. PMID- 7774372 TI - Survival of patients undergoing Nd-YAG laser therapy compared with Nd-YAG laser therapy and brachytherapy for malignant airway disease. PMID- 7774373 TI - Needle aspiration biopsy and ultrasonic guidance. PMID- 7774374 TI - Failure to achieve adequate serum levels with monthly replacement therapy in alpha 1-antitrypsin deficiency. PMID- 7774375 TI - Monitoring hemodynamics and blood gases during fiberoptic bronchoscopy. PMID- 7774376 TI - Primary site of lung cancer with systemic metastasis. PMID- 7774377 TI - Hypoxic lactic acidosis. PMID- 7774378 TI - Aspirin-induced asthma and artificial flavors. PMID- 7774380 TI - Bayes theorem. Diagnostic testing for tuberculosis in children. PMID- 7774379 TI - Reduce sympathetic hyperreactivity. PMID- 7774381 TI - Waiting for a phone call. PMID- 7774382 TI - A specific protein found in human senescent fibroblasts. AB - The limited potential for proliferation of human fibroblasts in culture represents cell level senescence. Aging is a programmed process under genetic control, and at certain stage of the life-span of animal cells, some genes start to express. Studying the biomarkers of senescent cells is important to understanding the basic mechanism of aging which may be relevant to the normal cell growth control and tumor biology. A protein with 72,000 Dalton molecular weight was detected by the hybridoma method in our laboratory. The protein shows specificity to senescent or presenescent cells of several cell lines, including WI-38, K.D., U2OS, etc. PMID- 7774383 TI - Quadrilateral space syndrome. AB - We studied 4 cases of quadrilateral space syndrome. Though the syndrome is quite uncommon, it might be discovered by examination of the patient complaining of pain of neck and shoulder especially when the tenderness in the quadrilateral space. Early surgical decompression is indicated as soon as diagnosis is made. PMID- 7774385 TI - Magnetic resonance imaging and microsurgical treatment of intramedullary hemangioblastoma of the spinal cord. AB - Thirteen cases of intramedullary hemangioblastoma of the spinal cord were studied radiologically, especially with magnetic resonance imaging (MRI). Microsurgery was used to remove the tumors in all cases. Signs and symptoms were improved in 84.6% of the cases after operation. The diagnosis and microsurgical techniques for excision of intramedullary hemangioblastoma of the spinal cord are discussed. This disease should be differentiated from hydromyelia, intramedullary ependymoma, and vascular malformation of the spinal cord. Total removal of the tumor is recommended. PMID- 7774384 TI - Experimental renal artery stenosis and angioplasty. The mechanism of the angioplasty. AB - The mechanism of percutaneous transluminal renal angioplasty (PTRA) was studied in 18 dogs. The dogs were divided into two groups. Seven dogs were in the early group and eleven were within 1-3 weeks after PTRA. A 4/0 resorbable chronic catgut was used to ligate subtotally the renal artery to create fibromuscular dysplasia. PTRA was performed after renal artery stenosis for 6-8 weeks. The changes of ultrastructure of renal artery were studied. A contrary orientation balance hypothesis was proposed to explain the mechanism of PTRA. PMID- 7774386 TI - Management of the orbital contents in radical surgery for squamous cell carcinoma of the maxillary sinus. AB - We reviewed retrospectively 139 patients with squamous cell carcinoma of the maxillary sinus who were treated with planned combinations of preoperative radiotherapy and maxillectomy between 1958 and 1987. The 5-year survival rate of these patients was 30%. In 111 patients who had tumor invasion of the orbital floor 88 underwent radical surgery with orbital exenteration and 23 had their orbital contents preserved. If orbital exenteration was performed, the 5-year survival rate was 27.3% (24/88) and the rate of recurrence within the orbit was 12.5%. In patients with preservation of the orbital contents, the corresponding rates were 34.8% (8/23) and 8.6% respectively (P = 0.65). Histological study after maxillectomy with orbital exenteration showed that in 95% of 65 specimens (62/65) invasion of the orbit was limited. These tumors could be completely resected by total maxillectomy with limited removal of the periorbital tissues after preoperative radiotherapy. We conclude that after preoperative radiation, the eyeball could be safely preserved in most selected patients with maxillary sinus carcinoma invading the orbital floor. PMID- 7774388 TI - Quantitative study of AgNOR in differential diagnosis between non-Hodgkin's lymphoma and reactive hyperplasia. AB - The argyrophilic staining technique was used in differential diagnosis between non-Hodgkin's lymphoma (NHL) and reactive hyperplasia (RH) of lymphatic tissues in 30 cases of RH and 71 cases of NHL which were classified as low (11 cases), moderate (49 cases) and high malignant (11 cases) groups. The number and the area of Ag nucleolar organizer region (AgNORs) in 100 cells of each case were examined by both IBAS-200 cytoimage analyser and microscope. The results showed that there was significant difference in the number, but not in area, of AgNOR granules between RH and low malignant group of NHL (P < 0.001). In NHL, the significant differences in the number and area of AgNORs were found between each groups (P < 0.05 or P < 0.001). It was also observed that in NHL, the number of AgNOR was negatively correlated with the area of the granules, and the shapes and distribution patterns of AgNOR were significantly different between each groups. Our results suggest that the quantitative study of AgNOR combining with the histological characteristics is very helpful in the differential diagnosis of RH and NHL and in the classification of NHL. PMID- 7774387 TI - Morphology and morphogenesis of hepatitis E virus (strain 87A). AB - The morphology and morphogenesis of isolated hepatitis E virus (HEV, strain 87A) were observed by electron microscopy (EM) and immune electron microscopy (IEM). Progressively developing local vesicles, virions accumulation in crystalline arrays and viroplasmic focus were seen in cytoplasm of infected cells. Replication and assembly of the new generation viruses were closely associated with rough endoplasmic reticulum (RER), inclusion body (IB) and microfibrils. Condensation and margination of chromatin, dispersion of nucleolar material, nuclear membrane alteration and masses of threads, granular material, and fibrillar component of the nucleus were frequently found. These changes revealed that this strain virus was confirmed as a RNA virus. The shape of the virus particles appeared approximately spherical whether the specimens were from the tissue culture crude suspension or purified highly concentrated preparations. The size of the virion was about 30 nm in diameter. The viral particles appeared unsmooth and irregular in outline. The spike-like structures may be occasionally observed on the surface of some viral capsides. The diameter of the strain 87 A virus is larger than the picornavirus and smaller than the calicivirus. This strain virus is different from classical calicivirus in without the cup-shaped surface depressions. The new genus, heparnavirus genus of caliciviridae family should be proposed for HEV. PMID- 7774389 TI - Rapid diagnosis and treatment of chlamydial conjunctivitis. AB - During December 1989 to December 1992, conjunctival specimens from 63 patients with severe trachoma and 30 with acute follicular conjunctivitis at the eye clinic of Tong Ren Hospital in Beijing, were tested by using direct immunofluorescent technique and amplified enzyme-linked immunoassay (Micro Trak and IDEIA) for chlamydial antigenicity. Trachoma accounted for 97.6% while acute follicular conjunctivitis accounted for 2.4% of the positive cases. Micro Trak and IDEIA tests proved advantageous over the culture method for the detection of Chlamydia trachomatis. In our study, Ofloxacin eye ointment has been proved to be an alternative drug for severe trachoma with better curative effectiveness. PMID- 7774390 TI - Applications of antisense RNA and DNA in cardiovascular research. PMID- 7774391 TI - Extrinsic compression of the lower ureter by a patent umbilical artery. Report of two cases. PMID- 7774392 TI - The national symposium on unstable angina pectoris. Classification, pathophysiology and management. PMID- 7774393 TI - Neurochemistry in China. PMID- 7774394 TI - Strive to prevent and control diabetes in China. PMID- 7774395 TI - Lymphocytic and erythrocytic k+, Na+, Ca++, Mg++ content in patients with congestive heart failure. AB - The content of lymphocytic and erythrocytic K+, Na+, Ca++, Mg++ changed in patients with congestive heart failure, related to clinical treatment and prognosis. The longer the course of disease, the more significant the changes, with no relation to the etiology of heart disease. The changes were partially improved after treatment of the heart failure. The content of electrolytes is not significantly different in patients in NYHA Class III, compared to those in NYHA Class IV. The metabolic changes of electrolytes occur on the myocardial cells, skeletal muscle cells and peripheral erythrocytes in patients with congestive heart failure. However, serum electrolyte content does not reflect precisely overall electrolyte metabolism in the body. Whether similar changes of electrolyte content occur in the peripheral lymphocytes is rarely reported. We studied the lymphocytic and erythrocytic electrolyte content in patients with congestive heart failure, to provide some reference in the clinical treatment and prognosis of congestive heart failure. PMID- 7774396 TI - Experiment study on the effect of Sheng-Mai injection on the contractivity of diaphragm and its mechanism. AB - In this study the effect of Sheng-Mai Injection i.e. Red Ginseng-Ophiopogon Root Injection (one kind of traditional Chinese medicines) on the contractivity of diaphragm was observed. The results confirmed that Sheng-Mai Injection increased Pdi of the fatigued diaphragm in rabbits and reduced the time needed for the recovery of Pdi of fatigued diaphragm to the normal value. These results suggest that Sheng-Mai Injection can increase the contractive force and promote the recovery of the fatigued diaphragm. The effect of Sheng-Mai Injection on the contractivity of the isolated diaphragmatic bundle of rats was also observed and the results confirmed that Sheng-Mai Injection increased the diaphragmatic contractive force directly. This effect of increasing the contractive force of diaphragm was attenuated by adding calcium channel blocker isoptin and disappeared when there was no calcium in the extracellular fluid. It is deduced, therefore, that the mechanism of the effect of Sheng-mai Injection is related to the increased influx of calcium from extracellular fluid into the cells. PMID- 7774397 TI - Platelet activation in patients with chronic pulmonary heart disease. Effect of dipyridamole treatment. AB - Plasma levels of beta-thromboglobulin (beta-TG), platelet factor 4(PF4) and platelet aggregation rate (PAR) were measured in remission phase of 15 patients affected with chronic pulmonary heart disease (CPHD). beta-TG, beta-TG/PF4, PF4 and PAR were significantly higher in the patients than in controls (P < 0.01 and 0.05, respectively). After 10 days of treatment with Dipyridamole 100mg tid, beta TG, beta-TG/PF4 and PF4 decreased significantly compared with pretreatment values (P < 0.01 and 0.05, respectively). The results suggest that in vivo platelet activation is indeed present in patients with CPHD and that dipyridamole can antagonize platelet activation in vivo. PMID- 7774398 TI - Therapeutic effects of photosensitizers in combination with laser and ACNU on an in vivo or in vitro model of cerebral glioma. AB - This study investigated the independent and combined effects of photodynamic therapy (PDT), laser photodynamic hyperthermia (LPDH) and 1-(4-amino-2-methyl-5 pyrimidinyl) methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) in a rat 9L induced gliosarcoma model. The mortality rate (MR60), mean survival time (MST60), and increasing life span (ILS60) within 60 days were determined to evaluate the therapeutic effect in vivo. The MR60 and MST60 of the gliosarcoma tumor control were 100% and 16.2 days. The ILS60s of PDT and ACNU were 72.84% and 49.81%, respectively, but MR60 of both were 86.72%. All combined treatments produced significantly prolonged survival (P < 0.01). The combined effects of LPDH and ACNU, MR60, MST60, and ILS60 were 60%, 43 days, and 165.4%, respectively. The ILS60 of PDT + ACNU (96.48%) and PDT + LPDH (98.58%) also indicated a synergistic or additive effect. The survival fraction and synthetic rate of DNA, RNA, and protein of glioma 9L tumor cells in vitro after single treatment of PDT or combined with antitumor drugs and laser showed that the cytotoxicity of PDT to 9L tumor cell was obvious by using Rh123, HPD, and Pf-II as photosensitizers. Combined treatments of PDT, antitumor drugs, and laser suppressed the synthesis of DNA, RNA, and protein more significantly than single treatment with PDT. PMID- 7774399 TI - [An experimental study on brain-gut peptide receptors in brains of rats with hepatic encephalopathy]. AB - By means of radioligand binding assay, two brain-gut peptide, somatostatin (SS) and vasoactive intestinal peptide (VIP), receptors in crude synaptosomal membranes of brain were investigated in rats with hepatic encephalopathy (HE) and in controls. In HE rats and in controls, the maximal binding capacity (Bmax) were 238.0 +/- 14.2 and 200.0 +/- 11.3 fmol/mg of protein, the dissociation constant (Kd) was 3.99 +/- 0.22 and 3.89 +/- 0.34 nM respectively for SS receptors. The Bmax values of VIP receptors in HE rats and in controls were 9.56 +/- 0.29 and 10.92 +/- 0.44 fmol/mg of protein, the Kd values were 0.28 +/- 0.01 and 0.29 +/- 0.02 nM, respectively. Increased Bmax values of SS receptors (P < 0.005) and decreased Bmax values of VIP receptors (P < 0.002) were observed in HE rats as compared with those in controls. The results suggest that changes of brain-gut peptide receptors in brains play a significant role in the pathogenesis of HE. PMID- 7774400 TI - [Hepatic hemodynamic changes in liver cancer patients during intrahepatic arterial angiotensin II infusion induced hypertension and chemoembolization]. AB - In this report, hepatic hemodynamics were studied by pulsed ultrasound doppler during the process of intrahepatic arterial angiotensin II infusion induced hypertension and chemoembolization (IHCE) in 20 liver cancer patients. It was found that at 90 seconds after I-HCE, tumor blood supply increased by an average of 1.786 times while the blood flow of proper hepatic artery decreased to an average of 0.5665 times of its original level. At the same time patients' peripheral blood pressure increased by 3.7kPa. It is evidenced that angiotensin II infusion augments blood flow to tumor region while decreases blood supply in healthy tissues. PMID- 7774401 TI - [A measurement of liver volume and its changes in post-hepatitic cirrhosis]. AB - By use of the computerized digital image processing system, the liver volume in vivo was successfully measured and the three dimensional image of the liver rebuilt in 62 cases of posthepatitic cirrhosis and 15 noncirrhotics. It was found (1) The liver volume of 474.64 +/- 115.28cm3/m2 in Chinese cirrhotics is significantly smaller than that of the control (P < 0.001); (2) In most cases, patients in class I of the liver function have a larger liver volume; (3) Patients with smaller liver volume have poor tolerance to surgery with a critical value of 400cm3/m2; (4) the liver volume considerably reduced after shunt plus devascularization but did not change after devascularization only. PMID- 7774403 TI - [The surgical treatment of gastric stump cancer: an analysis of 26 cases]. AB - 26 patients with gastric stump cancer were treated by surgery plus chemotherapy or radiotherapy in our hospital from 1970 to 1992. 20 patients were qubiected to surgery plus chemotherapy 12 patients were operable six patients had simple radiotherapy. These patients were followed up to the end of 1992. Using Kaplan Meier method and log-rank test (P < 0.05), we analysed the factors effecting the survival rate and drew a conclusion that surgical treatment plus adjuvant chemotherapy is the treatment of choice, and if no-resection, we would treat it with chemotherapy rather than radiotherapy. PMID- 7774402 TI - [Portal vein embolization via a fine needle guided by angio-echography: experimental and clinical study]. AB - This paper introduced a technique of portal vein embolization by injection of ethanol via fine needle under guidance of angio-echography. First introportal ethanol injection were done in 28 dogs to evaluate its embolic efficacy and safety. The result showed if a dose of injected ethanol was chosen properly, expected embolization could be obtained with slight toxicity to hepatic parenchyma and function. For clinical application, selective portal vein puncture was percutaneous transhepatic under echo guidance. Ultrasound angiography by injecting carbon dioxide (CO2) into portal vein was introduced initially. After confirmed that the injected branch was that supplied the tumor and there was no retrograde overflow of portal blood, ethanol was injected at a dose no more than 10ml. Eighteen patients with hepatocellular carcinoma and underlying liver cirrhosis underwent the procedure preoperatively. Of 14 cases who received hepatectomies, portal vein embolization developed in 12. Since the procedure was guided by angio-echography it could be used for indicated cases with satisfactory embolic effect and not harmful to liver. The procedure had advantages of simple manipulation and made selective embolization easier compared to interventional transcatheter portal vein embolization. PMID- 7774404 TI - [Air plethysmography in the diagnosis of primary venous insufficiency of lower extremities]. AB - Through the assessment 101 limbs of 77 subjects by air plethysmography (AP), we studied the method of AP test and the values of various indices in diagnosis of primary venous insufficiency (PVI). Venous filling index (VFI) was found valuable to quantitate the venous reflux with its value beyond the threshold of 5 ml/sec. It has a potential value to assess the effect of operations on PVI, such as valvuloplasty aiming to abolish venous reflux. Ejection fraction (EF) was found to be abnormal with its value less than 40%. It may be used to evaluate the function of calf pump quantitatively, predict the ulcer formation, and help make a decision of surgery timely. The comprehensive analysis of VFI, EF, RVF (residual volume fraction) and AVP (ambulatory venous pressure) indicated that there seems to be different types of PVI: type 1, low ejection (low EF) high venous reflux (high VFI); type 2, high ejection low venous reflux; type 3, low ejection low venous reflux. This new classification may impose some on the selection of adequate therapies, which will be further investigated. PMID- 7774405 TI - [Occult breast cancer: 9 cases report and review]. AB - From 1977 to 1994, 9 breast cancer were treated. All patients presented axillary node enlargement as first sign. Six patients were treated by radical or modified radical mastectomy and 3 by axillary node excision. All patients received postoperative adjuvant radiotherapy and chemotherapy. Among the 6 patients treated by radical or modified radical mastectomy, 4 survived over 10 years after surgery, 1 died of heart disease at 8 years, and 1 on chemotherapy is for 4 months. The three patients treated by axillary node excision, all died of the disease at 8-32 months. It is considered that radical or modified radical mastectomy with adjuvant radiotherapy and chemotherapy is a suitable treatment selection for occult breast cancer. PMID- 7774406 TI - [Study on the collagen of the different region of disc and different sigmental disc]. AB - With the method of the collagen decomposition producting special hyoroxyprolines (HYP), the collagens of the different region of discs and different segmental discs were studied. The results were as follow: The fibrous annulus had a higher collagen content than did the nucleus pulposus (P < 0.001). In fibrous annulus, the inner region had a lower collagen content was found at the postolateral part of the fibrous annulus (P < 0.05), especially at the poster-lateral inner zone (P < 0.001). The local low-collagen content at the particular location may be one of the factors, which was clinically susceptible to a disc herniation at the part. An increasing graduation of collagen content was found from thoracic disc12 to lumbar disc 5. But, there was no statistically significant difference (P > 0.05). PMID- 7774407 TI - [Lumbosacral lipomas with spinal bifida]. AB - Spinal dysraphism is usually accompanied with lumbosacral lipoma. The neurological deficits such as lower extremities sensorimotor disturbances, bowel and bladder dysfunction are produced by tethering, compression of lipoma and direct transmission of external force on the spinal cord during growth period. 25 patients treated surgically at our hospital between May, 1985, and January, 1993, were reviewed. Surgical approach was designed for debulking the lipomatous mass, untethering and decompressing the cord, repairing the dural defect and paraspinal muscle cleft. 2-59 months (mean 37.5 mons) after operation the 2 patients whose neurological system were normal before operation remained intact. In other 23 patients, bowel function recovered in 75%, active urination restored and improved in 66.2%. Motor dysfunction and paresthesia of the lower extremities alleviated in 78.3%. A case of mild uremia returned to normal and another moderate case improved. None was deteriorated by the operative procedure except one case in which a posterior nerve root was injured. PMID- 7774408 TI - [Video-assisted thoracoscopic surgery for pulmonary wedge resection]. AB - Video-assisted thoracoscopic surgery (VATS) wedge resection of lung has largely become a practical surgical procedure because the development of instruments and surgical techniques. The safety and feasibility are more remarkable comparing with standard surgical procedure. From November, 1992 to March, 1994, twelve patients suffering from pulmonary mass were underwent VATS. VATS wedge resection in 10, VATS pulmonary mass biopsy in 2. No operative death and severe complications occurred in this group. We discussed the clinical classification, indication and the surgical technique in this paper. PMID- 7774409 TI - [Occlusion with interrupted titanium clips for ruptured bullae under video assisted thoracoscopic surgery]. AB - Spontaneous pneumothorax is a common disease and as many as 20% of these patients should be operated because of a recurrent pneumothorax, persistent air leak, or failure to completely reexpand the lung. From January 1993 until March 1994, on the basis of experiment, we performed video-assisted thoracoscopic surgery (VATS) intervention and talc pleurodesis on 8 patients with spontaneous pneumothorax caused by ruptured bullae, and designed a new procedure of occluding the bullae with interruptured titanium clips. This procedure has some advantages of complete occlusion of lung tissue at the base of the bulla, minimal loss of lung tissue, effectively preventing leakage and recurrent pneumothoraces, and enough capacity of anti-tension while the lung expands. Also Authors have advocated giving a negative pressure suction to opsilateral lumen of the Carlen's tube interbation to visualize adequately the intrathoracic structures, while selective lung ventilation is performed. This method keeps hemodynamic stability and is performed more easily and safely than that of positive pressure insufflation is done. Postoperatively, complete lung expansion was obtained in all patients. There were no perioperative complications related to VATS, and no recurrences to date. These early results with thoracoscopic management of spontaneous pneumothorax caused by ruptured bullae have encouraging. PMID- 7774410 TI - [Video-assisted thoracoscopic surgery for chest disease]. AB - Video-assisted thoracoscopic surgery was applied in a total of 20 patients, since Dec. 1992. There were 16 man and 4 woman whose ages ranged from 20 to 65 years. Three patient had a wedge resection for lung tumors, one a lobectomy for tracheaectasy, eleven with recurrent spontaneous pneumothorax were successfully treated, Pleural tumors (n = 1), pulmonary cyst (n = 1), Three biopsy of lung. The advantages of this for patients include cosmetic considerations, a shorter operation period, low pain, earlier postoperation mobilization. PMID- 7774411 TI - [Non-operative regions extradural hematoma: a review of 5 cases]. AB - The authors report five patients who developed non-operative regions extradural hematoma following removal of intracranial tumors (3 cases) or cystiform diseases (2 cases). 3 cases developed on the left hemicerebrum. 2 cases formed on the bilateral. 4 cases were supratentorial operations, one inferior tentorial. The causative mechanisms of hematoma formation were attributed to a rapid fall in intracranial pressure, an increased blood velocity and the patient's position during the operation. Unexplained cerebral swelling during operation or delayed post-operative recovery should be intensely investigated by CT scanning. An emergency operation is indicated when the hematoma volume is more than 30ml. PMID- 7774412 TI - [Study of mechanism of selective head cooling-dehydration combined therapy for brain resuscitation: effect on function of brain cellular membrane]. AB - We induced cerebral complete ischemia (CCI) by "four-vessel" model. The changes of Na+,K(+)-ATPase, Ca2+, Mg(2+)-ATPase, phospholipase A2 (PLA2), total phospholipids on brain cellular membrane (BCM) at 30, 180, 360 min of reperfusion following 30 min CCI were observed. The effects of selective head cooling (SHC, 28C, surface cooling method), mannitol dehydration (MD), and selective head cooling-dehydration combined therapy (SHCDCT) on these changes were also investigated. Compared with non-ischemic, during reperfusion activities of Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase decreased while PLA2 increased (P < 0.001), phospholipids decreased at 180 and 360 min of reperfusion (P < 0.01). SHC and SHCDCT blocked all above changes, MD had no effect. These results suggest that SHCDCT after starting reperfusion do promote recruitment of BCM function by blockade of the successive reperfusion damage on BCM. PMID- 7774413 TI - [The effects of injection salviae miltiorrhizae in preventing and treating fat embolism syndrome]. AB - This study was to examine the effects and mechanisms of injectio salviae miltiorrhizae (ISM) in preventing and treating fat embolism syndrome (FES), which was simulated by intravenous injection of homologous bone marrow fat in 16 dogs. PaO2, free fatty acids (FFAs), TXA2/PGI2, SOD/MDA were measured in different times combined with X-ray, conjunctiva microcirculation observation, radioisotope scanning and histologic examination. It was found that in the control group there were a significant fall in PaO alpha and rise in FFAs and MDA; blood clot stained with oil red O showed many fat droplets; radioisotope scanning revealed mild hypoperfusion or perfusion defects. In the treatment group, arterial oxygen levels were maintained, serum level of FFAS and MDA was reduced significantly. It is concluded that there is damage induced by oxygen-derived radicals in FES, LSM is an effective therapy for the FES, and 99mTc radioisotope scanning is a promising technique for noninvasive identification of FES in the early stage. PMID- 7774414 TI - [Surgery of thymoma]. PMID- 7774415 TI - [Expression of WT1mRNA: relation to histology in Wilm's tumor]. AB - The mRNA expression of WT1 gene was examined by Northern blot and Dot blot hybridization in 13 Wilm's tumors of varying histology, 2 normal kidneys (1 and 5 years of age) and 1 fetal kidney (5 months of gestation). RESULTS: (1) WT1 gene expression was much higher in fetal kidney than in normal kidney of children; (2) Wilm's tumors which were predominantly epithelial or blastemal expressed high amounts of WT1mRNA, whereas predominantly stromal tumors expressed low amounts (P < 0.01). The data suggests that (1) there is a relationship between WT1 gene expression and cellular differentiation in kidney development; (2) low level expression of WT1mRNA results in disruption of cell differentiation and development of Wilms' tumor which shows stromal-predominant histology. PMID- 7774416 TI - [Timing of radical operation on Hirschsprung's disease in newborns]. AB - From June 1987 to June 1993, 42 neonates with Hirschsprung's disease (NHD) were treated with modified Duhamel's procedure. The follow-up from 2 months to 5 years (mean 30 mons) showed satisfactory results in all survivors. Comparing with 21 infants with Hirschsprung's disease treated (IHD) with modified Swenson's method showed that: (1) The follow-up results of NHD were better than IHD; (2) The extent and degree of hypertrophy and dilatation of proximal and transitional segment were less serious in NHD and the length of resection was shorter than that of IHD (NHD: 14.5-24.1 cm, IHD: 33-40.5 cm); (3) The degree of pathological changes such as mucosal inflammation, ulcer formation, and degeneration of ganglion cells was related to the age, duration and the length of agangliosis. Hirschsprung's disease has a chronic progressive course. Early operation can decrease the secondary structural and functional damage to the intestine. PMID- 7774417 TI - [The shunt for portal hypertension in children]. AB - Ten children with portal hypertension were treated with shunt operations. Among them, 9 were extrahepatic and one was intrahepatic lesion. The follow-up for 1-14 years showed: (1) In the 3 patients treated with splenopneumopexy, hemorrhage from the esophageal varices were controlled and portopulmonary shunt was demonstrated by Doppler ultrasound and radionuclide; (2) In the 6 patients treated with mesocaval shunt, 3 were non-recurrent bleeding and 2 died of recurrent bleeding or other disease respectively; (3) In one child with hepatic cirrhosis (11 year old) treated by splenorenal shunt, non-recurrent bleeding occurred. The authors suggest the portopulmonary shunt by splenopneumopexy is safe and effective for the portal hypertension of children. PMID- 7774418 TI - [Treatment of pediatric late stage neuroblastoma]. AB - From 1960 to 1992, 62 children with late stage neuroblastoma (stage III-IV) were admitted to our hospital. 24 (1960-1982) treated with operation and routine chemotherapy all died in 24 months after operation. And in 38 (1983-1993) treated with operation and high dose chemotherapy (including auto-bone-marrow transplantation + three times dose VM26 + routine chemotherapy in 3 cases, high dose chemotherapy + resection of tumor + high dose chemotherapy + routine chemotherapy for 4 years in 27, and dumbbell neuroblastoma in 8), 24 cases (63.%) still lived up to now. In which 11 cases (28.9%) lived more than 5 years and other 13 cases middle survival stage was 26.9 months. The high chemotherapy couldn't be instead of operation but it might produce a favourable condition to radical operation and thereby increase the effect of the operation. PMID- 7774419 TI - [A transposition of iliopsoas in replacement of pelvic floor for incontinence of urination and/or defecation in children]. AB - Fourteen patients, the age ranged from 2 to 12 years, with fecal and/or urinary incontinence were treated between 1991 and 1993 using a transposition of iliopsoas in replacement or strengthening of pelvic floor. The results were encouraging. The evaluation of the function of pelvic floor was described. Levator plays an important role in normal mechanism of defecation as well as urination. Several types of incontinence develop while the disfunction of pelvic floor occur and some function of continence could be restored by an operation of transposition of iliopsoas. PMID- 7774420 TI - [Infantile indirect inguinal hernia treated with laparoscopy high ligation of hernial sac]. AB - 22 cases of infantile indirect inguinal hernia were treated with laparoscopy high ligation of hernial sac. They were followed up for 9-18 months, the primary results were satisfactory and quite encouraging. The merits of this newly developed method are: The technique is relatively simple and less of postoperative complications. The technique and key point of the method were described in detail. PMID- 7774421 TI - [Surgical treatment thoracoabdominal aortic aneurysms with blocking of aorta at short intervals]. AB - Visceral ischemia and deterioration in renal function is common cause of morbidity in patients with thoracoabdominal aortic aneurysm surgically treated. Two patients with huge thoracoabdominal aortic aneurysm were surgically treated by a new technique of shunting. The operation was performed by using a synthetic artificial graft, which was sutured to the iliac artery by end to side anastomosis, and the upper end of the graft was anastomosed to the cut end of the thoracic aorta by end-to-end method. Compared with the traditional temporary shunting, there are several advantages in using the improved shunting technique. First, by so doing the ischemic time of various viscera could be fractionated and shortened, just about 17 minutes. visceral ischemic complication can be avoided. Second the pseudoaneurysm produced by the traditional method of temporal shunting could be prevented by the improved method. Third, on account of the ischemic time of the viscera is decreased, operation could be done under normal temperature without need for hypothermia. In treating a case of huge thoracoabdominal aortic aneurysm, successful result could hardly be obtained without good prepostopoerative care. We should also emphasize that the improvement of some surgical technique is also important. PMID- 7774422 TI - [Surgical treatment of left ventricular aneurysm]. AB - From April 1972 to Dec. 1993, 152 cases underwent operation for left ventricular aneurysm (LVA) in Fuwai hospital. There were 143 males and 9 females with mean age of 49 years. Patients underwent ECG, chest X-ray (C/T 0.42-0.71), echocardiogram (LVEDP 0.267-6.27 kPa and cardiocoronary angiography (LVEF13-69%). There were 58 cases (38%) in NYHA class II, 82 cases (54%) in class III and 58 cases (7%) in class IV preoperatively. The total operative mortality was 9% with 7% of the last six-year. The main cause of the death was refrectory low cardiac output syndrome. Univariate analysis showed that the operative risk factors included ventricular arrhythmias, preoperative congestive heart failure (< 1 month), poor NYHA class, A-V condaction block. 138 discharged cases were followed up from 2-215 months (mean 36). There were 11 late deaths. The five-year and ten year survival was 90% and 55% respectively. At the latest follow-up 44 cases (35%) were in NYHA class I, 62 (49%) in class II, 6 (6%) in class III and 2 (2%) in class IV. Our report demonstrated CABG is an effective treatment with good early and late results for LVA. PMID- 7774423 TI - [Surgical treatment of constrictive pericarditis in 162 cases]. AB - The authors reports the experience of surgical treatment of constrictive pericarditis in 162 cases. Age ranged from 6 to 66 years old. The cardiac function and circulatory dynamics were improved after decortication of the thickened pericardium in most of the patients. Overall surgical mortality was 3.1%. The major cause of death was low cardiac output syndrome in the early postoperative period. The authors consider that the excision of the thickened pericardium is better to begin from the left to right and the good perioperative management particularly the rational agents is essential in the prevention of low cardiac output syndrome. PMID- 7774424 TI - [Surgical treatment of middle lobe carcinoma of the lung]. AB - From February 1965 to April 1993, 88 patients with middle lobe carcinoma of the lung were treated surgically. It constituted 7.7% of the total patients of operated lung cancer in our hospital. Clinical symptoms were mainly fever, cough, bloody-sputum and chest pain. 84 of 88 patients were treated by wedge resection, lobectomy and pneumonectomy. Exploration was preformed in 4 patients. The 1, 3, 5 and 10-year survival rates of the 78 patients followed up were 87.18%, 43.08%, 38.18% and 24.13% respectively. It related to four clinical features of middle lobe cancer of the lung were treated surgically is discussed. PMID- 7774425 TI - [Further experience in the diagnosis and treatment of sphenoidal ridge meningioma]. AB - 72 cases with sphenoidal ridge meningioma operated on in recent 12 years in our department were reported. In the microsurgical group and non-microsurgical group, the rate of total removal of medial tumors was 65% and 20% respectively (P < 0.01); lateral tumors was 100% and 77% respectively (P > 0.05); the mortality was 6.7% and 11.9% respectively (P > 0.05); the rate of neurological impaired was 33.3% and 64.3% respectively (P < 0.001); good rate of following up for a long time was 87.5% and 16.7% in medial group respectively (P < 0.05); 66.7% and 75% in lateral group respectively (P > 0.05). It is believed that application of CT and angiography and microsurgical technique is helpful to the diagnosis and treatment of sphenoidal ridge meningioma. PMID- 7774426 TI - [Surgical treatment of pituitary adenoma]. AB - Seventy-four patients with pituitary adenoma were treated by surgery, including 51 transsphenoidal and 23 transcranial approaches, without death, postoperative leakage of CSF and early-period intracranial infection. Many patients had a transient diabetes insipidus after operation. In discussion we attended the difference of attacking age of pituitary adenoma between male and female, the significances of CT and MRI as well as the indication and the important points of various approaches. PMID- 7774428 TI - [Changes in gut hormones after Roux-en-Y cholangio-jejunostomy]. AB - In order to explore the mechanism of secondary gastric acid hypersecretion after Roux-en-Y Cholangio-jejunostomy (CJR-Y), we studied the changes of gastric acid secretion and determined the levels of somatostatin (SS), gastrin (Gn), neurotensin (NT), beta-endorphin (beta-EP) in serum, gastric juice and pyloric antrum in patients with CJR-Y. The results showed that gastric hypersecretion developed, levels of SS in those specimens decreased significantly and the content of Gn increased obviously after CJR-Y; whereas the content of NT and beta EP did not change significantly. We concluded that the decreased level of SS plays a role in the mechanism. PMID- 7774427 TI - [Two-stage multivariant analyses for prediction of hepatic function reserve]. AB - Eleven liver function tests were used for preoperative estimations of the hepatic function reserve in 103 patients with primary hepatocellular carcinoma (HCC) and underlying liver cirrhosis. Postoperatively, the patients' liver function could be classified as good recovering (Grade A, n = 38), functional damage (Grade B, n = 37) and liver failure (Grade C, n = 28). Single factor analyses showed 6 of those tests were significant indicators, including the ratio of blood glucose level at 120 minutes and 60 minutes by oral glucose tolerance test, total bilirubin, the ratio of albumin and globulin, prealbumin, prothrombin time and indocyanine green retention at 15 minutes. The correlations between 11 preoperative parameters (xi) and postoperative course scored (Y) were analysed by Fisher's discriminant test. The multiple regression equation Y1 was obtained by comparing from groups of Grade A with B and formula Y2 from groups of Grade B with C. The predictive accuracy of both equations were 88.0%, 83.1%, respectively. To select adequate surgical procedures with the best therapeutic effect and minimal liver damage for the patients with HCC, we proposed a method of "two-stage predications" combining use of Y1 and Y2 for evaluation of liver function reserve. PMID- 7774429 TI - [Dilatation of stricture of anastomosis after reconstruction of esophagus]. AB - This article reports the experience of the esophagus dilating technique in the treatment of 658 cases of postoperative anastomotic stricture for esophageal cancer and cardiac cancer during the period from May 1983 to May 1993, being delated add up to 3240 times with total effective rate 96.5%, among them 61.6% of the cases less than five, 84.5% of the cases less than ten. Of them, 27 cases (4.1%) had postoperative complications, of which the main ones were esophagus perforation 8 cases (1.2%), hemorrhage of anastomotic stoma 4 cases (0.6%), mediastinitis 1 case (0.2%) and loca trauma 14 cases (2.1%). The operative indication, surgical technique and complication were discussed. PMID- 7774430 TI - [Clinical application and technical problems of colonic interposition for esophageal substitution]. AB - From Jan. 1980 to Jan. 1991, A total 41 patients, including 22 patients with corrosive stricture after esophageal chemical burns, 10 patients with cancer of the laryngopharynx, 7 patients with esophageal cancer and 1 case of cardiac carcinoma, underwent of colonic interposition for esophageal substitution. This accounted 0.7% of all of the esophageal reconstruction during the same period. There were 23 cases of retrosternal colonic bypass and 18 cases of trans-hiatal inversion-stripping esophagectomy without thoracotomy. The main postoperative complications were anastomotic leakage at the cervical region and incision infection, but no mortality. The indications, choice of the colonic segment and the technical problems of this operation were discussed. PMID- 7774431 TI - [The application radionuclide bone imaging in the treatment of hallux valgus]. AB - Radionuclide bone imaging (RNBI) was performed by means of 99mTc-MDP on both 20 health subjects (40 feet) and 20 patients with hallux valgus (26 feet). The results showed that radioactivity intake were increased in second (or third) metatarsal of 26 feet of hallux valgus. The ratio of radioactivity of the lesion and contralateral normal site (D/N) had statistical difference (P < 0.01). Both the patient and normal groups RNBI is a highly sensitive study and valuable for the classification of diagnosis. It help for selection of surgical treatment, as to evaluate the results of the treatment. PMID- 7774432 TI - [The compensatory changes of unstriped muscles of portal vein and superior mesenteric artery in rabbits infected with schistosomiasis]. AB - We observed the changes of unstriped muscle of portal vein and superior mesenteric artery in rabbits infected with schistosomiasis in different stages with Masson trichrome stain. The results showed compensatory hypertrophy and hyperplasia of unstriped muscle of internal and medial layer of portal vein and superior mesenteric artery. It is concluded that the portal system is volume vessel as well as resistance vessel, which can counteract the intrahepatic resistance, maintaining the liver blood flow supply. The hyperdynamic circulation of viscera contributes to elevation of constrict power of the superior mesenteric artery, resulting in compensatory hypertrophy and hyperplasia of the unstriped muscle. PMID- 7774433 TI - [The experiment research of OB glue used in tracheoanastomosis]. AB - Resect a segment of canine cervical trachea. The length of resected trachea is from 1-4cm and 5-8cm. In the first group, one dog was used for each length and two dogs were used for each length in the second group, therefore twelve were used in the experiment. The upper and lower ends were matched and seved by three stitches, and OB glue was used to coat in the anastomosis crevice, and at last the cre-vice was wrapped with a sheet of loose tracheal sheath. After the operation, irritating cough, barking, swallowing and free movement of neck didn't cause fistula. Nakedeyes and tissue examination showed that the healing of the anastomostic orifice was well and no stenosis was found. The glue membrane was absorbed completely within 1-2 months. Outside body anti-pulling force experiment (for 8 cases) showed that the anastomostic line can hold 100cm H2O stress and 2kg pulling strength if only OB glue was used to connect the resected ends. Hence, this experiment shows that the usage of OB glue for tracheal anastomosis is a safety, simple and convenient method. PMID- 7774434 TI - [The study of repairing ability of freeze-dried bone allograft]. AB - There were many methods to preserve allogeneic bone allograft, however, a lot of studies have shown that the freeze-dried bone allograft banking is the best one. But it is not clear what temperature to lyophilize the allograft is better. In this experiment, we used method, in which the temperature of lyophilization was raising naturally and regularly, to lyophilize the allograft. The repairing ability of the freeze-dried allograft was studied in rabbits and comparison was made with that of autograft and fresh allograft. The results indicated that the repairing ability of bone defects was not significantly different between autograft and freeze-dried allograft. There was no significant difference between autograft and fresh allograft 3 weeks after transplantation, but significant difference was noted 8 weeks after grafting. It is suggested that this might be associated with the latent period before immunological rejection and the method itself, in which the temperature of lyophilization raising naturally is beneficial. PMID- 7774435 TI - [Progress in the preparation of bone allografts and their clinical uses]. PMID- 7774436 TI - [Experimental and clinical studies of small bowel allotransplantation]. AB - The pigs with allograft were divided into 5 groups according to the different immunosuppressive regimens. Acute rejection of allograft occurred in animals not treated with immunosuppressive agents or treated with low dose of cyclosporine (CsA). There was no rejection developed in the pigs treated with high dose CsA or low dose CsA and tripterygium wilfordii (TW). No evidence of chronic rejection was detected in animals with continued administration of TW after living longer than 100 days when the immunosuppressive treatment was discontinued. A woman with enterocolitis, ileus and short-gut syndrome received a complete cadaveric small bowel transplantation in march 12, 1994. The graft had 6 minutes for warm ischemia and 9 hours and 45 minutes for cold ischemia. The immunosuppressive therapy consisted of CsA, TW and methylprednisolone. The patient is alive and the function of graft is normal. PMID- 7774437 TI - [Application of gasless laparoscopic device in laparoscopic surgery]. AB - The aim of this study was to evaluate the gasless laparoscopic device (GLD) in laparoscopic surgery. GLD, independently designed and manufactured by ourselves in 1993, incorporates a manipulator and laparoscopic abdominal retractor. From August to October 1993, we conducted an experimental study on gasless laparoscopic cholecysto-duodenostomy in 5 dogs. Four of them were completely successful and one was converted to open surgery due to gallbladder rupture. The result showed that GLD could maintain good exposure in laparoscopic surgery, laparoscopic suturing and knotting could become easier and operative cost could be reduced with conventional instruments. We also developed an intracorporeal "Chinese Knotting" and a self-designed push tube for extracorporeal knot tying. During April and August 1994, we successfully applied our modified GLD in gasless laparoscopic cholecystectomy, inguinal herniorrhaphy laparoscopic-assisted sigmoidectomy, abdomino-perineal resection of rectal carcinoma. PMID- 7774439 TI - [AgNOR, DNA ploidy and prognosis in colorectal cancer]. AB - A follow-up study with special reference to nucleolarorganizer region-associated protein (AgNOR) and DNA ploidy was conducted in 83 consecutive cases of colorectal cancer patients who underwent radical surgery at the people's Hospital, Beijing, from 1982 through 1986. Counting on the mean number of AgNOR showed a predominant difference between the tumor tissue (9.796 +/- 3.670) and normal mucosa (2.937 +/- 0.812), (P < 0.001). With regard to the tumor differentiation, the number of AgNOR was paralleled with the degree of malignancy of the tumor, 8.178 +/- 2.864 for well differentiated tumors, 10.086 +/- 3.940 for moderately differentiated tumors and 11.577 +/- 2.824 for poorly differentiated ones. Patients with lower AgNOR (< 10) tumor had a prominent survival advantage over those with AgNOR > or = 10 tumor. Particularly when combined with the factors of DNA ploidy and AgNOR, prognosis of patients with diploid tumor and AgNOR < 10 was more favorable than that of those with aneuploid and AgNOR > or = 10 tumor. PMID- 7774438 TI - [Effects of over feeding on the energy expenditure and substrates oxidative rate in surgical patients]. AB - In this study, computerized indirect calorimetric measurements were made using a medical graphics critical care monitor (CCM) desktop analysis system in the observation of metabolic state of 20 patients complicated with external gastrointestinal fistula. While these malnourished patients were provided with 1.5 x REE in total energy intake, the malnutrition state could be reversed. But with 1.75 or 2.0 x REE or up total energy intake, the general nutritional state could not be improved faster, the O2 consumption and CO2 production and energy expenditure increased, while the net glucose oxidation increased and net lipid oxidation decreased or net lipogenesis occurred simultaneously. We believed that superfluous energy intake is harmful to critically ill patients and may lead to cell injury and dysfunction. PMID- 7774440 TI - [Inhibition of antisense DNA and its derivative on gastric transformed cell carcinogenicity]. AB - In this study, an antisense c-Ha-ras DNA was synthesized. It was a complementary oligonucleotide chain to the sequence of initiation position of c-Ha-ras gene transcription. We found that the antisense DNA blocked the gene expression at the level of transcription and translation and partially reverted the malignant phenotyped of gastric transformed cells, including their growth rate, colonies formation in soft agar, tumorigenicity in nude mice and different grade. When the 5'-end of the antisense DNA was covalently linked with psoralen group, its biological effects were significantly enhanced. No effect of tumor inhibition was found in control oligonucleotide chains not complete complementary to the sequence of target gene. These results indicate that antisense DNA and its derivative are effective in tumor gene therapy. PMID- 7774441 TI - [Study and clinical application of tumor-infiltrating lymphocytes isolated from hepatocarcinoma]. AB - Tumor-infiltrating lymphocytes isolated from freshly resected tumors of 12 patients with hepatocarcinoma were propagated in vitro and infused to patients. The average weight of tumor for culture of TIL was 4.8g, number of cells 5.8 x 10(7), time for in vitro expansion was 31.8 days. The maximal expansion achieved 1000 fold, with a mean amplification rate of 198.5 fold. LAK cell culture supernatant stimulated TIL growth. 10 of 12 patients received clinical treatment, the number of cells infused reached 4 x 10(8)-1.1 x 10(10). TIL was infused by hepatic artery. TIL isolated from hepatocarcinoma demonstrated cytotoxic activity to tumor targets. PMID- 7774442 TI - [Evaluation of the prognosis of critically ill surgical patients by APACHE II score system]. AB - A prospective trial was conducted in 386 critically ill surgical patients, the APACHE II score was used to quantify the severity of illness and to judge the outcome. Admission APACHE II score of these patients averaged 15.6 +/- 5.4, the mortality rates rose from 1.9% to 100% when the APACHE II score increased from 0 to 38. The score was closely correlated with the subsequent risk of hospital death for these patients (r = 0.75 P < 0.001). Critically ill surgical patients would be well served by APACHE II for quality assurance or outcome. PMID- 7774443 TI - [The effects of combined hepatectomy and immuno-chemotherapy on postoperative recurrence rate of primary liver cancer]. AB - 121 cases with primary liver cancer were divided into four groups: OP: resection only (30 cases); OC: combined operative resection and chemotherapy (27 cases); OI: combined operative resection and immunotherapy (31 cases); OI: combined operative resection and immuno-chemotherapy (33 cases). The results showed that one year recurrence rate was 56.7%, 40.7%, 32.3% and 27.3%, respectively. The recurrence rate of group OI and group OIC were significantly lower than that of group OP and group OC. It indicated that combined operation and immuno chemotherapy is useful in preventing post operative recurrence. PMID- 7774445 TI - [Dynamic cardiomyoplasty: first successful clinical case in China]. AB - A 35-year-old man with chronic heart failure (NYHA Class III) caused by dilated cardiopathy was selected for dynamic cardiomyoplasty. The procedures were completed in one stage. The left latissimus dorsi muscle was mobilized and wrapped around the heart. A set of medtronic cardiomyostimulator system (A Medtronic Model SP 1005A Cardiomyostimulator, two Medtronic Model SP 5528 intramuscular leads, and two medtronic Model 5701-35 Cardiac screw-in leads) was implanted. The postoperative sequential progressive skeletal muscle electrostimulation was started two weeks after cardiomyoplasty. The final electrostimulated parameters were: 6 pulses, amplitude 2.75 V, synchronization delay 75 ms, pulse width 210 us, synchronization delay 75 ms, pulse width 210 us, synchronization ratio 2:1, frequency 30 Hz, stimulation duration 185 ms. The patient recovered very well. After four months, patient's status improved to NYHA Class I. Echocardiography, MUGA, and catheterization studies showed a significant improvement in hemodynamic parameters (MUGA LVEF increased from 15% to 24%, SVI increased from 21.7 ml/beat/m2 to 50.6 ml/beat/m2: CI increased from 2.699 L/min/m2 to 3.59 L/min/m2. PMID- 7774444 TI - [Predictors of hepatic functional reserve in cirrhotic patients]. AB - We have determined the interstitial ratio, hepatocyte numerical density on area (NA) by the method of Luzex-F Image Analyser, and the level of serum prealbumin (PA), choline esterase activity (ChE) by agarose immunodiffusion and ratemetry in control group (14 cases) and 25 cirrhotic patients undergoing pericardial devascularization. The results were compared with traditional hepatic function grade (Child's Grade). We found that NA, PA, and ChE are independently useful in evaluating the hepatic functional reserve in cirrhotic patients. PMID- 7774446 TI - [Congenital kinking of the aorta: report of 5 cases]. AB - 5 patients with congenital kinking of the aorta, one male and 4 females with a mean age of 29 years (age range, 10-37 years), underwent surgical-treatment. There was a systolic murmur at the left sternal border and the interscapular area and hypertension only in the right arm. A chest rentgenogram showed a widened left superior mediastinum. Angiograms showed elongation, kinking and aneurysm formation of the aortic arch and descending aorta and the aneurysm ruptured in one. Three patients were associated with coarctation of the aortic arch, one with coarctation of the upper descending aorta and another with interruption of the aortic arch. All the patients had an excellent results. The clinical features, morphology, surgical techniques and postoperative care were discussed. PMID- 7774447 TI - [Clinical fracture of joint prostheses]. AB - Ten Ti6Al4V joint prostheses, including 8 hips and 2 knees, were fractured after 1 to 13 years in vivo service following the primary arthroplasty. The metallographs and electronic microscopies, taken from the retrieved components, demonstrated that there are typical characteristics of stress corrosion fatigue. The excessive chemical content of raw material, the presence of interior defects, such as inclosures and porosities, incorrect design features, which violate biomechanic principles, the overheating and improper surface finishing of the parts, and the clinical varus positioning of the hip stem contribute to the device failure. Policies are proposed to overcome this problem. Among them are drawing national mandatory standards on surgical implants, taking strigent administration measures to ensure the quality of joint prostheses and the establishment of training centers for arthroplasty. PMID- 7774448 TI - [Absorbable SR-PGA implant in orthopaedics: preliminary results of treatment of fractures]. AB - This article reports preliminary results of treatment in 33 patients with 36 cancellous bone fractures using absorbable rods and screws of self-reinforced polyglycolide (SR-PGA). Plaster cast was used postoperatively for 3 weeks. All fractures but one lateral ankle fracture were fixed until healed without displacement. All of them healed at six weeks after trauma. No wound infection and fluid accumulation occurred. This new device is an ideal implant for fixation of cancellous bone fracture. PMID- 7774449 TI - [Anatomy and clinical application of transcervicothoracic polyphyletic blood supply skin flap]. AB - Transcervicothoracic skin flap was used to repair the faciocervical scars left after burns in 56 cases. Anatomy and clinical application proved that the transverse cervical artery branches out a constant skin artery before it enters the trapezius muscle and this artery, after crossing the clavicle, is divided into two branches, one extending outwards, and the other downwards. The internal thoracic artery branched out an intercostal perforator on the spot 1 cm to the parasternum. The perforator extended along the intercostal plane and belonged to the direct skin artery. The rate for perforation between the second and third ribs was the highest and the diameter of the perforator the greatest. The thoracoacromial skin artery perforated through the medialsemis between the greater pectoral muscle and the deltoid muscle, and extended toward the shoulder, supplying the skin of the infraclavicular, deltoid and upper greater pectoral regions with blood. Anatomy and contrast examination showed that there are extensive anastomoses between the three groups of blood vessels. On the basis of these anastomotic branches, transregional skin flaps can be designed to repair faciocervical damages. These flaps were successfully used in the 56 cases, with 32 cases having the the branch of cervical segment of the trasverse cervical artery as the pedicle, and 24, the second and third perforators of the internal thoracic artery as the pedicle. It was proved that the transregional flaps can be successfully transferred regardless of the sites of the pedicles. PMID- 7774450 TI - [Endodermal sinus tumor of the testis in children: report of 9 cases]. AB - Nine children with endodermal sinus tumor of testis have been treated since 1982. Their age ranged from 7 months to 5 years. Radical inguinal orchiectomy was carried out in all the patients. Four patients have received irregular chemotherapy. The follow-up showed that 4 died of the metastasis within 5 years and 5 (stage I clinically) survived without evidence of the recurrence for 1.5-7 years after operation. Serum AFP determination may give important information for the classification of the tumor and the evaluation of the follow-up results. For the cases of clinical stage I, radical orchiectomy, short course of chemotherapy, and frequent observations of AFP level are advocated. PMID- 7774451 TI - [A clinical study of inhibition of secondary cataract with heparin]. AB - Extracapsular cataract extraction with posterior chamber lens implantation was performed on 47 eyes with senile cataract of which 25 eyes were in the control group and 22 eyes were irrigated with heparin solution (25U/ml) in the operation, the drug group. Postoperatively, 2 eyes with hyphema were found in the drug group, but the deposition of fibrin and cells on the anterior lenticular surface and the posterior capsular opacification were significantly less than those in the control group. 3 months after the operation, the mean visual acuity in the drug group was 0.70 +/- 0.26 markedly higher than that in the control group, 0.54 +/- 0.28 (P < 0.05). PMID- 7774453 TI - [A clinical analysis of pupillary membrane formation after intraocular lens implantation]. AB - In 540 cases having undertaken extracapsular cataract extraction and intraocular lens implantation, a pupillary membrane developed in 76 cases, the rate of occurrence being 14%. Generally, the membrane appears on the fifth post-operative day and corticosteroids are effective in its treatment. After treatment no significant sequela is left and the corrected postoperative visual acuity is not affected. The pathogenesis, treatment and prognosis of the pupillary membrane are briefly discussed in the report. PMID- 7774452 TI - [Cataract extraction and intraocular lens implantation in patients with uveitis]. AB - Thirty two patients with uveitis had a posterior chamber intraocular lens implantation after extracapsular cataract extraction. After a mean follow-up period of 5.4 months (range 3 to 29 months), the corrected visual acuity in 93.7% of the patients reached to 0.5 or better. Postoperative complications included posterior capsule opacification and iris posterior synechiae. The results suggest that careful selection of candidates for IOL implantation be crucial for successful cataract surgery in uveitis patients. PMID- 7774454 TI - [Vitrectomy combined with posterior chamber intraocular lens implantation in complicated ocular injuries]. AB - Posterior chamber intraocular lens implantation combined with lensectomy vitrectomy and/or removal of intraocular foreign bodies in one operation was performed on 12 patients with ocular injuries involving both anterior and posterior segments. There were 6 cases with intravitreal or intraretinal foreign bodies, 3 cases with lens dislocation in the vitreous by blunt trauma and 3 cases with vitreous hemorrhage and cataract. Pre-operatively, the visual acuities of all patients ranged from light perception to 0.02, while postoperatively, their visual acuities were 0.5-1.5 in 8 cases, 0.3 in 2 cases, finger counting and 0.05 in other 2 cases which were related to optic nerve atrophy and retinal vein occlusion, respectively. The results suggest that the combined surgery benefit the fast visual rehabilitation in selected young patients with unilateral ocular injuries. PMID- 7774456 TI - [A clinical analysis of subclinical siderosis and secondary glaucoma]. AB - In this study, we reported 6 cases of retained iron-containing intraocular foreign body with no signs of siderosis but manifestations of secondary open angle glaucoma. The clinical characteristics and the possible mechanism of this form of glaucoma were described. It is proposed to name this special and easily neglected glaucoma "subclinical siderosis secondary glaucoma". PMID- 7774455 TI - [Complicated cataract after vitrectomy and gas-liquid exchange]. AB - Cases with complicated cataract occurring after vitrectomy and gas-liquid exchange were reported. In a consecutive series of 62 eyes having undertaken the operation, a transient cataract developed in 8 eyes and an irreversible cataract in 28 eyes. The manifestation of the transient cataract is the posterior subcapsular opacity, feathery or placoid vacuolar in clusters in appearance. It was found that if the amount of the residual vitreous at the retrolental space is great enough, the chance of occurrence of complicated cataract is less. That the direct contact of the gas with the lens affects the lens metabolism and nutrition is the chief cause of the development of the cataract. It is suggested that to prevent the development of cataract induced by the gas, besides selection of body posture, quiet stay in bed and proper selection of gas type, the vitreous at retrolental space be resected as little as possible. PMID- 7774457 TI - [Magnetic resonance imaging in 80 cases of orbital tumors]. AB - Magnetic resonance imaging (MRI) is a new medical imaging technique which has been used in evaluating ocular and orbital diseases in recent years. Owing to the high resolution of soft tissues and lesions, it is superior to ultrasound and computed tomography in the localization and characterization of an orbital tumor in diagnosis. In this paper, we analysed 80 cases of MR images of orbital tumors by which all the lesions were detected. Benign or malignant disorders were recognized in 59 cases and complete tumors with accurate localization were shown in 79 cases. The principles of MRI, signal intensity of various tumors and the indications of MRI were discussed. PMID- 7774458 TI - [A study on risk factors of retinopathy of prematurity]. AB - Ocular fundi of 54 premature infants (age of gestation < 37 weeks) and 5 full term babies with low body weight (< 2500 g) were examined at the forth week after birth. According to the international classification of retinopathy of prematurity, they were diagnosed as retinopathy of prematurity (ROP). The risk factors of the incidence of ROP were statistically analyzed, respectively. The results show that the lower the body weight, the shorter the gestation, the higher the oxygen concentration, the longer the oxygen administration, the higher the incidence of ROP. The incidences of ROP in the following baby groups, the body weight at birth < or = 1500 g, gestational weeks < or = 32 weeks, the oxygen concentration administered > 80%, and the duration of persistent oxygen administration > 5 days are significantly higher than those in the corresponding respective other groups. It is also demonstrated that the duration of the first time of oxygen administration and the complications of the newborn babies such as asphyxia, intracranial hemorrhage, anemia, pneumonia and blood transfusion have no effects on the incidence of ROP. PMID- 7774459 TI - [Treatment of myopic anisometropia by radial keratotomy]. AB - 18 cases of myopic anisometropia were treated by radial keratotomy (RK). The preoperative myopia in eyes with higher degrees of refractive error ranged from 3.25 to -11.00D (mean = -6.53D), the anisometropia ranged from -2.50 to -11.00D (mean = 4.95D) and the visual acuities of the naked eyes were 0.02 to 0.15 (mean = 0.08). A half year after the operation, on the average, there was a 0.46 increase in visual acuity, -4.57 D decrease in myopia and -3.60D decrease in anisometropia. Postoperatively, 14 cases had regained the binocular single vision and 6 cases had 60" stereoscopic vision which is in the normal range. Therefore, it is considered that RK operation not only can decrease myopic degree and increase visual acuity, but also can decrease or even eliminate anisometropia to facilitate the recovery of binocular single vision. In monocular or anisometropic myopia, if the corrected visual acuity of the myopic eye or the eye with higher degree of myopia in a case is not below 0.6, RK operation is indicated and if the anisometropia is lower than -9.00D, postoperatively, binocular single vision may be recovered. The preoperative examination of myopic anisometropia, the method of predicting prognosis and some attention points in the treatment are also mentioned in the paper. PMID- 7774460 TI - [A histopathologic study on lacrimal gland in Sjogren's syndrome]. AB - Biopsy specimens of palpebral lacrimal glands from 15 cases of Sjogren's syndrome (SS) were studied by light and transmission electron microscopy. Six cases without any symptoms or signs of dry eyes were used as the control. The main changes of SS included: (1) massive infiltration of lymphocytes; (2) atrophy of lacrimal glandular follicles and ducts in various degrees; (3) degeneration and necrosis of glandular epithelium; and (4) proliferation of connective tissue. Lymphatic infiltration indicates that the damage of the glandular tissue might be related to autoimmune pathogenesis. According to the histopathologic findings, the authors divide SS into three stages which are basically consistent with their clinical presentations. PMID- 7774462 TI - [A study on histopathology of iris with Nd: YAG and/or argon laser iridotomy]. AB - Laser iridotomy including Nd: YAG, argon and Nd: YAG combined with argon was performed on 42 eyes of 25 chinchilla rabbits. The postoperative follow-up was 8 months. The histopathological changes of the irides at the sites of the various laser shots under light, transmission and scanning electron microscopic examinations were compared. The results show: (1) In regard to the Nd: YAG laser effect on the target tissue, the inherent elasticity of the tissue may play a more important role in curative effects of the therapy than the thickness of the tissue. (2) Every iris hole, < 200 microns in diameter, performed by Nd: YAG or < 450 microns, by argon or argon combined with Nd: YAG was closed by the first postoperative week. The histopathological findings demonstrate that the pigment epithelial proliferation and migration are more marked in the irides with argon laser iridotomy. (3) An insufficient coagulative burn of the argon laser may cause congestion of iris blood vessels and possibly, result in more severe bleeding during succedent Nd: YAG laser shots. PMID- 7774461 TI - [Experimental studies on the changes of immunocytochemistry of gamma-aminobutyric acidergic neurons in the lateral geniculate nuclei of amblyopic kittens]. AB - 14 kittens at 2-4 weeks of age were randomly divided into normal (N) and monocular deprived (MD) groups. Before the MD amblyopic models were made, pattern visual evoked potentials (PVEPs) were elicited from the experimental eyes. After the closure of 7 unilateral eyes (right 3, left 4) with operation, the two kitten groups were fed for 12 weeks under a same visual environment. At the end of 12 weeks, PVEPs were re-examined and amblyopia was confirmed in the MD group. The gamma-aminobutyric acidergic (GABAergic) neurons in the layers A, A1 and C in the contralateral geniculate nucleus (CLGN) inputs from N and MD eyes were stained with antibiotin-peroxidase complex (ABC) method. The changes in number and grey degree of GABA immunopositive neurons in the layers A, A1 and C in CLGN inputs from N and MD eyes were analysed by a computer image analysis system. The results show that GABA immunopositive neurons are reduced in number and their grey degree is decreased in the layer inputs from MD eyes in the comparisons between the layers of inputs from MD and N eyes. The experiment indicates that (1) GABAergic neurons in the kitten lateral geniculate nucleus (LGN) are susceptible to visual deprivation during the postnatal critical period and their functions are dependent on the import of visual sense information and the retinal activity. (2) GABAergic neurons in the LGN act as regulators in dealing with and importing visual signal toward striate cortex. PMID- 7774463 TI - [Research on corneal thickness at multi-points in normal and myopic eyes]. AB - The corneal thickness of the center and other 24 points were measured in 31 normal eyes and 246 myopic eyes. The results show that the mean central corneal thickness of the normal eye is 541 +/- 45.29 microns and that of the myopic eye, 544 +/- 35.01 microns. There are no significant differences in the central corneal thickness in comparisons between the left and right eye, between the male and female, among various age groups, and among various degrees of refractive error. However, with the increase of age and increase of myopic refractive error, the central corneal thickness gradually becomes thinner. There are differences in thickness among various directions, the superior direction being the thickest and the temporal inferior, the thinnest. From the center to the limbus, the thickness of the cornea gradually increases, but the values of the increase of the thickness are various in various directions, that should be paid attention to in radial keratotomy. PMID- 7774465 TI - Harry E. Bacon Oration. Comparison of the functional results of restorative proctocolectomy for ulcerative colitis between the J and W configuration ileal pouches with sutured ileoanal anastomosis. AB - PURPOSE: This study was designed to compare function of patients who had undergone reconstruction following proctocolectomy for ulcerative colitis using the J or W configuration ileoanal pouch. METHODS: Of 126 patients who underwent restorative proctocolectomy between January 1981 and March 1993, 101 had surgery for ulcerative colitis. Eighty-seven of these patients were available for review by personal or postal interview. All operative procedures were performed by one surgeon. The group comprised 35 W-pouches and 52 J-pouches. RESULTS: More patients with a J-pouch had a stool frequency of greater than 8 per 24 hours (P = 0.044), and they were also more likely to use a perineal pad (P = 0.019). No difference in the rates of nocturnal stool frequency, fecal incontinence, or use of constipating agents between the two pouch designs was found. Significantly more patients with a J-pouch have had episodes of pouchitis (P = 0.001). Of the total patient group 91.9 percent felt that restorative proctocolectomy had improved their quality of life. CONCLUSION: Minor differences in the function of the W configuration ileoanal pouch and the J configuration ileoanal pouch are demonstrated in this study. PMID- 7774464 TI - [A method of measuring iris radius by computerized image analysis]. AB - A new method of measuring the iris contour has been set up with a personal computer. The model of a parabolic curve, an approximate mimic iris contour curve, was traced to define the profile contour of the iris from a photograph. A radius measured from the apex of the curvature of the parabola, named iris radius (IR), was calculated by a computer to describe the degree of the curvature of the iris contour. The iris radius of 93 eyes of 68 cases with early pupillary block primary angle closure glaucoma were measured by this method. The results show that the mean iris radius of cases with glaucoma is shorter than that of the normal age matched controls (53 cases 106 eyes) and there is statistical significant difference (P < 0.01). This method of measurement can be an effective method to further study the early diagnosis and pathogenic mechanism of the pupillary block angle closure glaucoma. PMID- 7774466 TI - Barnett continent intestinal reservoir. Multicenter experience with an alternative to the Brooke ileostomy. AB - PURPOSE: Since 1988, surgeons at five hospitals have been performing the Barnett continent intestinal reservoir (BCIR). The BCIR includes modifications to the original Kock pouch, designed to reduce the incidence of valve slippage and fistula formation. Principle modifications include an intestinal collar, an isoperistaltic valve, and a lateral pouch design. METHOD: This unique collaborative study includes 510 ulcerative colitis or familial polyposis patients, with a follow-up time from one to five years postoperatively. RESULTS: Ninety-two percent still have functioning reservoirs. Six and one-half percent have had their pouches removed and replaced with conventional Brooke ileostomies. Reoperation rate for major pouch-related complications (other than pouch removal) was 12.8 percent. These complications included slipped valve (6.3 percent), valve fistulas (4.5 percent), and pouch fistulas (6.3 percent). Several questions were administered to patients whose responses revealed a significant improvement in general quality of life, state of mind, and overall health. CONCLUSIONS: The BCIR represents a successful alternative to patients with a conventional Brooke ileostomy or those who are not candidates for the ileal pouch-anal anastomosis. PMID- 7774467 TI - Perianal injection of autologous fat for treatment of sphincteric incontinence. AB - PURPOSE: The aim of this study was to evaluate the results of treatment of partial fecal incontinence with perianal injection of autologous fat. METHODS: The study comprised 14 patients with partial fecal incontinence (9 women and 5 men). Ages ranged from 38 to 62 years. Fifty to 60 ml of fat were harvested from the abdominal wall and injected submucosally into the rectal neck at 3 and 9 o'clock positions. Mean follow-up was 18.6 months. RESULTS: All patients were continent during the first two to three postinjection months. At the sixth month, patients were divided into three scores. Score 1 (complete continence) comprised three patients who are now continent for 9, 11, and 14 months postinjection, with normalization of their rectal neck pressure. Seven patients with Score 2 were incontinent to flatus and were reinjected; they are now continent (Score 1) for a mean of 13.8 months and have normal rectal neck pressure. Four patients had Score 3 (no improvement), of whom two became continent after the second injection and two after the third. They are now continent (Score 1) 6 to 16 months postinjection. Factors that contributed to failure comprised injection of unwashed fat or wrong positioning of the needle. There was no fat migration or embolism. CONCLUSION: Perianal fat injection is effective in treatment of partial fecal incontinence. The technique is simple, easy, cost-effective, and performed on an outpatient basis. PMID- 7774468 TI - Frequency of hereditary nonpolyposis colorectal cancer. A prospective multicenter study in Finland. AB - PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early onset of colorectal carcinomas (CRC). Recently, two HNPCC genes have been mapped and cloned, one in the short arm of chromosome 2 and another in the short arm of chromosome 3. There has been a major controversy about the frequency of HNPCC. The few estimates available have been based on series selected by age or series representing local area. The purpose of the present study was to design a nonselected, prospective, multicenter study, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N = 406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of identifiable risk factors of CRC was 5.8-7.5 percent (HNPCC, 0.7 2.4 percent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; familial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospective multicenter study revealed that the frequency of hereditary colorectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent findings of common ancestral founding mutation in Finnish HNPCC families indicates that there may be geographic differences in the occurrence of HNPCC. However, this does not change the fact that identification of HNPCC--perhaps one of the most common inherited diseases identified in humans--has become a question of vital importance now when diagnosis of the syndrome and large-scale screening of gene carriers using specific tests are on the horizon. PMID- 7774469 TI - Colonoscopic bowel preparations--which one? A blinded, prospective, randomized trial. AB - For the past decade peroral, orthograde, polyethylene glycol-electrolyte lavage solutions (PEG-ELS) have been the preferred bowel-cleansing regimens before diagnostic and therapeutic procedures on the colon and rectum. The large volume and unpalatibility of these solutions may lead to troubling side effects and poor patient compliance. PURPOSE: This study was undertaken to determine which of various colon-cleansing methods before colonoscopy would provide greater patient acceptance while maintaining similar or improved effectiveness and safety. METHODS: Three hundred twenty-nine patients undergoing elective ambulatory colonoscopy were prospectively randomized to one of three bowel preparation regimens. Group 1 received 41 of PEG-ELS (n = 124). Group 2, in addition to PEG ELS, received oral metoclopramide (n = 99). Group 3 received oral sodium phosphate (n = 106). All groups were evenly matched according to age and sex. RESULTS: Ninety-one percent of all patients completed the preparation received. Sixteen percent of patients suffered significant sleep loss with a bowel preparation. When comparing the three groups, there was no difference in the assessment of nausea, vomiting, abdominal cramps, anal irritation, or quality of the preparation. Compared with other preparations, oral sodium phosphate was better tolerated. More patients completed the preparation (P < or = 0.001). Fewer patients complained of abdominal fullness (P < or = 0.001). More patients were willing to repeat their preparation (P < or = 0.02). Also, sodium phosphate was found to be four times less expensive than either of the PEG-ELS preparations. CONCLUSION: All regimens were found to be equally effective. Abdominal symptoms and bowel preparation were not influenced by the addition of metoclopramide. The oral sodium phosphate preparation was less expensive, better tolerated, and more likely to be completed than either of the other preparations. PMID- 7774470 TI - Laparoscopic-assisted colectomy learning curve. AB - PURPOSE: The purpose of this paper is to establish the number of cases necessary to master laparoscopic removal of the left or right colon. METHODS: Data were obtained by chart review and by individually completed questionnaires. RESULTS: A total of 144 laparoscopic-assisted or intracorporeal right or left hemicolectomies were completed by four surgeons at separate institutions. Questionnaires were completed by each surgeon for each sequential hemicolectomy, and data concerning the type of surgery and total operating time were recorded. Times were plotted to diagram individual learning curves for each surgeon, and data grouping methods were used to determine the curve for each surgeon as well as for the combined data base. Learning was said to have been completed when the surgeon's operative time reached a low point and subsequently did not vary by more than 30 minutes. A total of 78 right colectomies and 66 left colectomies were completed by the group. Respectively, each surgeon appeared to learn the procedure after 16, 21, 11, and 6 cases. When the entire database was analyzed as a whole, it was shown that between 11 and 15 completed colectomies were needed for learning, after which operative times remained relatively stable. CONCLUSIONS: This analysis, using total operative time as an indication of learning, shows that approximately 11 to 15 completed laparoscopic colectomies are needed to comfortably learn this procedure. PMID- 7774471 TI - Does the avoidance of nasogastric decompression following elective abdominal colorectal surgery affect the incidence of incisional hernia? Results of a prospective, randomized trial. AB - PURPOSE: In a previous, prospective, randomized study of the use of nasogastric tubes in patients undergoing elective abdominal colorectal surgery, we found that patients who did not have nasogastric (NG) decompression postoperatively had a significantly higher rate of abdominal distention, nausea, and vomiting. Patients from that study have now been followed for a median duration of 5.3 years to evaluate whether this elevation in perioperative intra-abdominal pressure would subsequently lead to an increased incidence of incisional hernia. RESULTS: Of the 251 patients who received NG decompression, 8 (3.2 percent) developed incisional hernias compared with 15 (6.6 percent) of 229 patients who were not decompressed (P = 0.085). CONCLUSION: The increase in postoperative abdominal distention and vomiting that occurs in patients who do not receive NG decompression does not lead to a significantly increased incidence of incisional hernia. Furthermore, we continue to support avoidance of routine prophylactic postoperative nasogastric decompression in uncomplicated, elective abdominal colorectal surgery. PMID- 7774472 TI - Hyperbaric oxygenation in severe perineal Crohn's disease. AB - PURPOSE: Perineal involvement in Crohn's disease is a common and distressing condition, often refractory to medical or surgical treatments. Recent reports suggest the efficacy of hyperbaric oxygenation (HBO) in the healing of perineal lesions. We evaluated HBO in severe patients with perineal Crohn's disease. METHODS: Ten consecutive patients (8 women, 2 men; mean age, 30 years) were studied. There were four superficial fissures, four cavitating ulcers, six low or superficial fistulas, two high fistulas, and one irreversible anal stenosis. All patients had received one or more medical treatments without healing the perineal lesions, and all had had previous surgery for perineal lesions. RESULTS: Two patients discontinued HBO after a few sessions and did not complete treatment. Eight patients completed at least 30 HBO sessions and were evaluable. At the end of the procedure, six of eight patients treated were healed, three completely and three partially. All patients who healed completely received HBO as an additional treatment to local perineal surgery. CONCLUSION: HBO might be useful as a last resort treatment of chronic perineal Crohn's disease, resistant to other treatments or as a complement to surgery. PMID- 7774473 TI - Fluctuation of blood pressure and pulse rate during colostomy irrigation. AB - PURPOSE: The aim of this study was to determine the effects of colostomy irrigation on the vital signs of patients with left colostomy. METHODS: Twenty two consecutive patients who underwent abdominoperineal resection for cancer of the lower rectum and had left lower quadrant end colostomy were included in this study. Subjective symptoms, blood pressure, and pulse rate during the first irrigation were investigated. RESULTS: Fluctuation of blood pressure during instillation was 8.0/8.5 mmHg (average) and 25.0/17.9 mmHg during evacuation. Fluctuation of pulse rate was 5.5 per minute (average) during instillation and 11.5 per minute during evacuation. The number of subjects who showed more than 20% fluctuation of systolic pressure was 12 (54.5 percent) and that of diastolic pressure was 14 (63.6 percent). One of 22 patients complained of illness during irrigation. CONCLUSION: Although colostomy irrigation showed no significant effects on vital signs in the majority of patients, it caused a significant reduction in both blood pressure and pulse rate in a small number of patients. Careful attention should be paid to vital signs considering the possibility of such effects, especially on the initial irrigation. PMID- 7774474 TI - Follow-up after curative surgery for colorectal carcinoma. Randomized comparison with no follow-up. AB - PURPOSE: This study investigated the value of intense follow-up compared with no follow-up after curative surgery of cancer in the colon or rectum. METHODS: One hundred seven patients were randomized to no follow-up (control group; n = 54) or intense follow-up (follow-up group; n = 53) after surgery and early postoperative colonoscopy. Patients in the follow-up group were followed at frequent intervals with clinical examination, rigid proctosigmoidoscopy, colonoscopy, computed tomography of the pelvis (in patients operated with abdominoperineal resection), pulmonary x-ray, liver function tests, and determinations of carcinoembryonic antigen and fecal hemoglobin. Follow-up ranged from 5.5 to 8.8 years after primary surgery. RESULTS: Tumor recurred in 18 patients (33 percent) in the control group and in 17 patients (32 percent) in the follow-up group. Reresection with curative intent was performed in three patients in the control group and in five patients (four of whom were asymptomatic) in the follow-up group. In the follow-up group two asymptomatic patients with elevated carcinoembryonic antigen levels were disease-free three and five and one-half years after reresection and were the only patients apparently cured by reresection. No patient underwent surgery for metastatic disease in the liver or lungs. Symptomatic metachronous carcinoma was detected in one patient (control group) after three years. Five year survival rate was 67 percent in the control group and 75 percent in the follow-up group (P > 0.05); the corresponding cancer-specific survival rates were 71 percent and 78 percent, respectively. CONCLUSION: Intense follow-up after resection of colorectal cancer did not prolong survival in this study. PMID- 7774475 TI - Long-term management of diverticulitis in young patients. AB - PURPOSE: This study was designed to determine the natural history of documented diverticulitis that resolves after treatment with intravenous antibiotics and bowel rest in patients under the age of 50. METHODS: Records of 40 patients aged 50 or under who were hospitalized with the diagnosis of acute diverticulitis between 1980 and 1984 were reviewed to obtain data regarding how the diagnosis was made. Patients successfully treated with antibiotics were contacted five to nine years after their attack and surveyed via telephone questionnaire about symptoms, recurrent attacks, and surgical interventions. RESULTS: A total of 40 patients were included in the study. Ten patients (25 percent) required surgery during initial admission, and 30 patients were discharged with resolution of their symptoms after treatment with intravenous antibiotics and bowel rest. A five-year to nine-year follow-up was obtained on patients treated medically, one third of whom underwent operation for diverticulitis during this period, and two thirds of whom did not require surgery during the follow-up period. All operations were elective with single-stage resections. CONCLUSION: Based on our data, we do not recommend surgery in this population after a single episode of diverticulitis that resolves after treatment with antibiotics. PMID- 7774476 TI - Pudendal neuropathy is not related to physiologic pelvic outlet obstruction. AB - Chronic straining because of pelvic outlet obstruction is hypothesized to cause pudendal neuropathy (PN) by stretch injury. PURPOSE: The aim of this study was to determine any association between PN and pelvic outlet obstruction. METHODS: One hundred forty-seven constipated patients were evaluated by cinedefecography and pudendal nerve terminal motor latency assessment. PN was defined as a latency longer than 2.2 ms. Pelvic outlet obstructive patterns of evacuation included paradoxic contraction, nonrelaxation of the puborectalis muscle, or failure of opening of the anal canal. RESULTS: Median length of constipation including straining during evacuation was eight (range, 1-47) years. Ninety-one (62 percent) subjects had a normal pattern of evacuation, and 56 (38 percent) had an obstructed pattern. Both groups had a similar median age (68 vs. 69 years, respectively; P > 0.05) and same median length of symptoms. Overall incidence of PN was 23.8 percent (10.9 percent unilateral and 12.9 percent bilateral). There was no difference in the incidence of PN between patients with normal evacuation and patients with obstructed evacuation (24.2 percent vs. 23.2 percent, respectively; P > 0.05). Patients with PN had a similar incidence of physiologic pelvic outlet obstruction as did patients without PN. However, median age of patients with PN was higher than those without PN (73 vs. 66 years, respectively; P > 0.05). CONCLUSION: There was a difference in the incidence of PN between normal and obstructed patterns of evacuation. Therefore, the espoused theory that obstructed defecation causes PN appears flawed. PMID- 7774477 TI - Subtotal colectomy with Hartmann's pouch for inflammatory bowel disease. AB - PURPOSE: Fulminant or unremitting colitis caused by inflammatory bowel disease (IBD) is effectively managed by subtotal colectomy (STC) and standard ileostomy. However, controversy exists regarding the optimal management of the retained rectum. We reviewed our experience with intraperitoneal Hartmann's closure to determine whether this is an acceptable way to handle the rectal remnant. METHODS: We retrospectively reviewed hospital and office records of 114 consecutive patients with IBD colitis who underwent STC with Hartmann's pouch since 1988. Patient demographic data, operative details, and postoperative complications were recorded. In patients who underwent subsequent surgery, technical difficulty and complications related to rectal dissection were documented. RESULTS: There were three instances of pelvic sepsis secondary to leakage from the Hartmann's pouch, an overall incidence of 2.6 percent. Two of these patients required exploratory surgery. The third patient responded dramatically to antibiotics and transanal catheter decompression of the Hartmann's pouch. Subsequent to this experience, patients undergoing STC and Hartmann's closure for IBD colitis had transanal catheter drainage of the rectal remnant as a routine part of their postoperative care. There were no instances of leakage among the 41 patients who underwent rectal decompression. There were two reports (3 percent) of technical difficulty in locating or mobilizing the intraperitoneal rectal remnant at 60 subsequent surgical procedures. CONCLUSION: Intraperitoneal Hartmann's closure of the rectum is the preferred management in patients with intractable IBD colitis requiring STC. PMID- 7774478 TI - Intestinal obstruction promotes gut translocation of bacteria. AB - PURPOSE: Translocation of enteric organisms has been implicated as a possible source of sepsis in susceptible patients. Animals studies have suggested that intestinal obstruction promotes bacterial translocation from the gut lumen. The aim of this study was to study the prevalence of bacterial translocation in patients with and without intestinal obstruction. METHODS: Serosal scrapings, mesenteric lymph nodes, and peripheral blood cultures were obtained from 254 patients. Scrapings and nodes were homogenized and incubated aerobically and anaerobically. Full-thickness biopsies underwent villous height analysis. The clinical course was followed for at least six weeks. RESULTS: Bacterial translocation to mesenteric nodes occurred more frequently in patients with large bowel obstruction than in patients without obstruction (14 of 36 patients vs. 16 of 218 patients; P < 0.001). Both aerobic and anaerobic bacteria were found to translocate. The more distal the obstruction, the more likely anaerobic bacteria were to be identified. Translocation of bacteria predisposed to postoperative septic complications (P < 0.05). Villous height was not related to bacterial translocation. CONCLUSIONS: Gut translocation of bacteria is more common in patients with intestinal obstruction, and its association with septic complications appears to be of clinical significance. PMID- 7774479 TI - Outcome of surgery for colorectal cancer in a defined population in Sweden from 1984 to 1986. AB - PURPOSE: This study was designed to investigate incidence, treatment, and outcome for patients with colorectal cancer. METHODS: From 1984 to 1986 in Ostergotland, a county in Sweden with a defined population, a prospective registration using a computerized protocol was undertaken. RESULTS: In the surgical departments 596 cases were diagnosed and 31 more cases were diagnosed in other departments, bringing the incidence to 53 cases per 100,000 inhabitants per year. Of the cases, 14 percent presented as emergencies. The resectability rate was 90 percent, and the rate of curative operations was 74 percent. Postoperative mortality within 30 days was 2.9 percent. Crude five-year survival for all patients was 40 percent, and the corrected survival rate was 53 percent. After curative resection the crude five-year survival rate was 53 percent, and the corrected survival rate was 70 percent. Prognosis was better for colon than for rectal cancer, 76 percent vs. 59 percent corrected five-year survival rate. For rectal cancer the local recurrence rate was 20 percent after curative resection. CONCLUSIONS: The prognosis was improved compared with a previous study from the same area because of decreased postoperative mortality, increased rate of operations for cure, and an increased five-year corrected survival rate. Local recurrence after rectal cancer was still high but may be reduced with improved surgical technique. PMID- 7774480 TI - Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma. AB - PURPOSE: Reduced expression of the metastasis suppressor gene nm23-H1 has previously been correlated with high tumor metastatic potential and fatal clinical outcome in some tumors (e.g., breast). For colorectal carcinomas, the findings are equivocal. METHODS: We have used a monoclonal antibody against nm23 H1 to investigate the expression in colorectal carcinomas at the time of primary curative surgery (R0 resection) to assess if there was any relation between nm23 H1 expression and stage or histologic grade at the time of primary tumor removal. RESULTS: Of 100 colorectal carcinomas studied (Stages I, II, and III according UICC, all resected curatively), nm23-H1 immunoreactivity was weak in 41 (41 percent), moderate in 24 (24 percent), and strong in 35 (35 percent) cases. The grade of positivity against nm23-H1 was significantly lower in advanced stages of the disease (Stages II or III) (P < 0.001, chi-squared = 52.8). In tumors with low or weak immunoreactivity against nm23-H1, frequency of lymph node metastases was significantly higher compared with those with moderate or strong staining (P < 0.001; chi-squared = 50.58). Therefore, with a sensitivity of 93 percent and a specificity of 58 percent, low nm23-H1 immunoreactivity of the primary tumor, assessed at the time of surgery, is an indicator of the presence of lymph node metastases. CONCLUSIONS: Immunohisto-chemical evaluation of nm23-H1 in the primary tumor or in a biopsy is a useful predictor of stage of disease and presence of lymph node metastases in colorectal carcinomas and may have clinical significance, e.g., in predicting optimal therapeutic regimes. PMID- 7774482 TI - Circular stapled rectal stricturoplasty with the Proximate intraluminal stapler. AB - PURPOSE: Benign rectal strictures arise from a variety of causes, and numerous techniques have been developed to deal with them. When even the most innovative methods of stricture treatment fail, major resection may be required. An alternative to resection is desirable. METHODS: A case is presented in which the Proximate curved intraluminal stapler was used to perform successful stricturoplasty of a low rectal stricture when other methods failed. RESULTS: Circular stapled rectal stricturoplasty provided a wide lumen, minimized perforation risk, and preserved continence. CONCLUSION: Circular stapled rectal stricturoplasty is an option to consider when other treatments for rectal stricture fail. PMID- 7774481 TI - Treatment of Hirschsprung's disease in the adult. Report of five cases. AB - PURPOSE: Between 1983 and 1991, five adult patients were diagnosed and treated for Hirschsprung's disease. Mean age was 37 (range, 13-45) years. Three patients had classic Hirschsprung's disease, and two had findings consistent with short segment disease. Each patient had a history of disabling, lifelong constipation. METHODS: Diagnosis was established with the aid of barium enema study, anorectal manometry, and tissue biopsy. RESULTS: Three patients with classic disease underwent resection of diseased bowel, rectal mucosectomy, and anastomosis between the ganglion-containing bowel and anus. All three patients had excellent functional improvement in the perioperative period. Two patients with findings consistent with short segment Hirschsprung's disease were treated by anorectal myectomy. Neither patient obtained lasting relief. PMID- 7774483 TI - Stapled stricturoplasty for Crohn's disease. A new technique. AB - PURPOSE: Stricturoplasty was originally used to treat multiple fibrotic strictures of tuberculosis. As the pendulum of treatment of Crohn's disease swung toward conservatism and bowel preservation, stricturoplasty was performed in Crohn's disease. Stricturoplasty can be used when there is limited, well localized disease and should be avoided in the presence of grossly inflamed or infected material. We describe a new technique of stricturoplasty. METHODS: Typically stricturoplasty is performed in a manner similar to a Heineke-Mikulicz pyloroplasty. A stapled stricturoplasty technique has been previously described, but in actuality these are more similar to a bypass procedure. Our technique uses a stapled, open technique similar to the triangulating method of bowel anastomosis. This was performed in one patient to correct six strictures. RESULTS: Our patient did well postoperatively and developed no significant complications. He has no evidence of recurrent strictures. CONCLUSION: We describe a stapled stricturoplasty technique that is truly a stricturoplasty because the bowel lumen is increased; it is similar to the triangulating method of end-to-end stapled bowel anastomosis. It is safe, efficient, and effective. Additionally, it allows radiographic location of the stricturoplasty site, thus allowing determination of effectiveness of the procedure as well as recurrence. PMID- 7774484 TI - Do nonsteroidal anti-inflammatory drugs prevent rectal carcinoma in familial adenomatous polyposis? PMID- 7774485 TI - Technical error caused by software. PMID- 7774486 TI - An unusual cutaneous presentation of metastatic colon carcinoma. PMID- 7774487 TI - Fine-needle aspiration cytopathology of soft tissue: chondromyxoid and myxoid lesions. AB - Soft-tissue lesions pose an intimidating challenge to diagnostic interpretation by fine-needle aspiration cytology. To better characterize such aspirates, we investigated a subgroup of lesions which yielded a large amount of chondromyxoid and myxoid stroma (CMS). Thirty-three cases (22 malignant lesions, 11 benign lesions) in which CMS was a prominent feature of the smears were studied. The most common malignant neoplasms were extraskeletal chondrosarcoma (6 cases), myxoid liposarcoma (6), and malignant fibrous histiocytoma (5). The benign entities consisted of ganglion cyst (4), myxoma (3), and neurofibroma (2). Of the aspirates from 22 malignant neoplasms, 15 (68%) contained opaque stroma, and in 18 (81%) the stroma was distributed as discrete clumps or fragments; all extraskeletal chondrosarcomas and chordomas contained these features. Additionally, in five of six chondrosarcomas the matrix exhibited cells within lacunae. Except for a tracheal chondroma which extended into the adjacent soft tissue, no benign aspirates had all three of these cytologic features. Twenty three aspirates (70%) were moderately or highly cellular; all but two of these were malignant. Moderate to marked nuclear atypia occurred in 13/22 (59%) malignant and 1/11 (9.0%) benign aspirates. With a few exceptions, aspiration smears of benign lesions with abundant CMS were characterized by low cellularity, semitransparent amorphous stroma, and lack of nuclear irregularity. Recognition of variations in the character of the background material in addition to traditional cytologic criteria can aid in the diagnosis of benign and malignant chondromyxoid and myxoid aspirates of soft tissue. PMID- 7774488 TI - Transtracheal needle aspiration. AB - A series of 27 transtracheal needle aspiration biopsies performed on 25 patients were reviewed. A rigid bronchoscope and rigid needle were used. The biopsies were performed as staging procedures in patients with bronchogenic carcinoma, or to obtain diagnoses in patients with mediastinal adenopathy. A cytopathologist attended 11 biopsies and microscopically examined a direct smear to determine adequacy. Repeat biopsies were taken at the time if necessary. A diagnosis was obtained in 9/11 (81%) of these cases. Only 3/16 biopsies (18.8%) performed in the absence of a pathologist were diagnostic. All negative cases were subsequently found to have disease (2 sarcoidosis, 13 cancer) by other methods including mediastinoscopy in 5 cases. In the patient group sampled, the technique of rigid needle and rigid bronchoscope with a cytopathologist in attendance resulted in a much higher sensitivity for the test than has been previously reported. PMID- 7774489 TI - Mucinous cystic tumor of the pancreas: an analysis of FNA characteristics with an emphasis on the spectrum of malignancy associated features. AB - Previously, pancreatic mucinous cystic tumors were classified as either benign (cystadenoma) or malignant (cystadenocarcinoma). Descriptions of the fine-needle aspiration (FNA) findings of these neoplasms have heretofore emphasized malignant cytologic characteristics. In the following, we present a summary of a study of FNA characteristics from ten patients with cystic mucinous neoplasms, four of whom have correlating histologic material. In this study, we found a spectrum of cytologic features ranging from completely benign appearing to obviously malignant. We discuss cystic mucinous pancreatic tumors and the associated FNA findings helpful in diagnosis and categorization of these neoplasms. Also, we suggest the inclusion of a new entity in the mucinous neoplasm category. PMID- 7774490 TI - Comparative cytologic findings of in situ and invasive adenocarcinoma of the uterine cervix. AB - The cytologic findings in 13 cases of cervical adenocarcinoma in situ (mean age 33.9 yr) were compared with those in 9 cases of cervical invasive adenocarcinoma (mean age 45.7 yr). All diagnoses were confirmed by biopsy. The major differences found were that a necrotic background (66% invasive vs. 0% in situ) and macronucleoli (77% invasive vs. 0% in situ) were more common in invasive cases, whereas associated squamous-cell dysplasia (69% in situ vs. 0% invasive) was more common in in situ cases. Other differences included syncytial tissue fragments with irregular cell borders, frequent cell drop-off, and markedly atypical single columnar cells (or markedly atypical naked nuclei) seen more commonly in invasive cases, whereas monolayer sheets and/or syncytial tissue fragments with smooth borders and rare cell drop-off were more common in in situ cases. Although none of these features is diagnostic individually, in combination they are helpful in distinguishing between in situ and invasive adenocarcinoma. Nine of 13 of the in situ cases showed associated squamous-cell dysplasia. In all nine of these cases, the glandular dysplasia was overlooked or underestimated in severity on original cytologic diagnosis. This suggests that the presence of a squamous lesion may lead to decreased detection of glandular lesions, perhaps because the features of squamous lesions are more well known; thus they are more easily recognized, at the expense of glandular lesions. All invasive adenocarcinomas were identified as carcinoma in the original diagnosis with seven specified as invasive adenocarcinomas. PMID- 7774491 TI - Benign spindle and inflammatory lesions of the breast: diagnosis by fine-needle aspiration. AB - We describe fine-needle aspiration (FNA) findings in 7 patients with breast masses showing numerous spindle cells in smear material. The benign nature of these lesions was confirmed by clinical follow-up (n = 4) or surgical excision with histologic examination (n = 3). The final diagnosis included one case each of myofibroblastoma, juvenile hypertrophy, post-FNA reactive stromal proliferation, stromal induction in proliferative fibrocystic disease, and subareolar abscess. There were two instances of granulation tissue. The case of stromal induction was initially felt to be suspicious for phyllodes tumor. The post-FNA stromal reaction was considered sufficiently atypical to warrant histologic investigation. The importance of historical and physical examination findings in accurate interpretation of these uncommon cases is emphasized. Some will require histologic assessment for final diagnosis. PMID- 7774492 TI - Subcutaneous masses of the scalp and forehead: diagnosis by fine-needle aspiration. AB - We report our cytologic findings and clinical correlations in benign (N = 2) and malignant (N = 16) subcutaneous masses of the scalp (N = 15) and forehead (N = 3), studied by fine-needle aspiration (FNA). Diagnoses were divided in 3 groups: (1) Scalp plasmacytoma (as a manifestation of multiple myeloma) (6 cases) was the most frequent diagnosis. In one patient it was the presenting manifestation of the disease. (2) Miscellaneous malignancies included 8 carcinomas, 1 melanoma, and 1 malignant lymphoma. The scalp or forehead mass was the initial presentation and FNA was the initial diagnostic approach in five patients. (3) A single case each of pilar-type keratinous cyst and hematoma were the only benign masses encountered. In conclusion, a significant number of subcutaneous masses of the scalp or forehead represent metastatic or systemic malignancies, and they may be the initial manifestation of the disease. Rapid and accurate diagnosis by FNA provides guidelines for appropriate therapy, especially in those patients who present with advanced disease. PMID- 7774493 TI - High grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression. AB - The cervical cytologic finding of a high grade squamous intraepithelial lesion (HGSIL) or carcinoma shortly following a negative smear is unusual. To determine if such cases are due to screening errors, inadequate sampling, or rapidly progressive lesions, a review of negative smears (immediately preceding a diagnosis of HGSIL or carcinoma by at most 2 yr) was performed on 17 patients (all such patients in our 1990-92 files, representing 6% (17/290) of such diagnoses). The time between negative smear and positive result averaged 9.3 mo. Eighty-eight percent of these patients had prior histories of a cytologic abnormality. Upon review, 16 of 17 "negative" smears contained a cytologic abnormality. Atypical immature squamous metaplastic type cells (AISMTs) were found in 11 of 16 cases, atypical squamous cells or slight dysplasia were found in 5 of 16, HGSIL was found in 5 of 16, and atypical cells of undetermined type and origin were noted in 1 of 16. Combinations of the above diagnoses were present in 6 of 16 cases. The number of abnormal cells per slide was estimated, with < 10 cells in 1 case, < 50 in 4 cases, 50-100 in 7 cases, 100-200 in 3 cases, and > 200 in 1 case. In this study, screening and/or evaluation errors were the dominant cause of false-negative cytologic diagnoses, with AISMTs accounting for the most commonly missed or misinterpreted cells. These cells are small and have hyperchromatic nuclei with elevated nucleus to cytoplasmic ratio and nuclear irregularities. PMID- 7774494 TI - Comparison of immunoreactivity of neu oncoprotein in fine-needle aspirates and paraffin-embedded materials. AB - Expression of the neu oncogene has been extensively examined in frozen and paraffin section breast cancers; however, very few studies examine neu oncoprotein oncoprotein expression in fine-needle aspirates. To this effect, we compared the expression of neu oncoprotein in formalin-fixed paraffin-embedded breast cancers and the corresponding fine-needle aspirates of these cancers. There was 100% correlation between the expression of neu oncoprotein in the paraffin-embedded breast cancers and the fine-needle aspirates, indicating the suitability of fine-needle aspirates for the expression of neu oncoprotein in breast cancers. PMID- 7774495 TI - c-erbB-2 in retrospect: is it time for molecular cytology? PMID- 7774496 TI - Renal hydatid cyst: urinary cytological diagnosis. AB - Echinococcal disease is endemic in many areas of Asia, Europe, South America, the Near East, Australia, and New Zealand. Hepatic and pulmonary cysts are the most common presentation. Isolated renal hydatid cyst is an uncommon presentation of echinococcal disease, since renal involvement occurs in only 2-3% of cases. We present the case of a young man with renal colic, in whom the diagnosis of renal hydatid disease was established cytologically. Urine cytology, performed because of persistent hematuria, revealed scolices of Echinococcus granulosus and prompted further imaging investigation, and, ultimately, surgical treatment. PMID- 7774497 TI - Pilomatrixoma: a description of two cases diagnosed by fine-needle aspiration. AB - The present work reports on the findings obtained by fine-needle aspiration of two pilomatrixomas located on the upper limbs whose diagnosis was confirmed histologically. In both cases, the cytology disclosed a proliferation of small round basaloid cells that were dispersed and grouped in clusters together with squamous cells and abundant multinucleate giant cells. The differential diagnosis with other neoplasms is discussed. PMID- 7774498 TI - Neuroendocrine carcinoma of the thymus: aspiration biopsy, immunocytochemistry, and clinicopathologic correlates. AB - We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. In all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear "buttons" found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. PMID- 7774499 TI - Primary lymphoma of bone: diagnosis by fine-needle aspiration biopsy in a pediatric patient. AB - We present an unusual case of a child with an isolated lytic lesion in the L3 vertebral body. Fine-needle aspiration biopsy showed a small, blue-cell neoplasm raising the differential diagnosis of Ewing's sarcoma and lymphoblastic lymphoma. Through a combination of morphologic and immunofluorescent findings we established a diagnosis of lymphoblastic lymphoma. This case further documents the utility of fine-needle aspiration biopsy in the diagnosis of pediatric tumors. PMID- 7774501 TI - Ultrasound guided fine-needle aspiration cytology: diagnosis of hydatid disease of the abdomen and thorax. AB - Eight cases of hydatid disease of the abdomen and thorax were diagnosed by fine needle aspiration (FNA) cytology under ultrasound guidance. The age of the patients ranged from 28 to 60 yr with a median of 34.5 yr; the male to female ratio was 2:6. None of the cases were diagnosed clinically as hydatid diseases but following ultrasonography suspicion of hydatid cyst was raised in two cases. The locations of cysts were the liver in six cases, the lung in one case, and the mediastinum in one case. FNA yielded clear fluid in five cases and turbid fluid in three cases. Laminated cyst wall, scolices, and hooklets were observed in one case, scolices and hooklets were present in two cases, and laminated cyst wall along with hooklets were seen in two cases. The remaining three cases showed only laminated cyst walls which yielded positive reaction with periodic acid-Schiff reaction. Inflammatory cell reaction in the form of neutrophils was observed in four cases, including the three cases where turbid fluid was aspirated. Epithelioid cell reaction was present in one case. None of our eight cases showed any untoward allergic reaction following FNA. PMID- 7774500 TI - Fine-needle aspiration cytology of adenoid (acantholytic) squamous-cell carcinoma. AB - Adenoid squamous-cell carcinoma (ASCCa) is an uncommon cancer which occurs most frequently in the skin of the head and neck region of elderly, sun-exposed individuals. Histologically, ASCCa is characterized by gland-like, "adenoid" cell groups with a central, detached acantholytic cellular component and an intact peripheral rim of cells. The cytological features of five fine-needle aspiration cytology (FNAC) samples from four patients with primary or metastatic ASCCa are presented. These were assessed for features which would allow distinction of this variant from conventional squamous carcinoma. The adenoid component was represented in FNAC by intact, sometimes three-dimensional cell groups simulating glandular structures. Also present were cells in short chains of two or three in single cell files and scattered, individual dyskeratotic cells. Individual cells had rounded, accentuated borders, cytoplasmic keratinization, and often pyknotic nuclei, representing acantholytic cells from the adenoid "lumens." Features of malignancy, including cellular atypia and increased mitotic rate, were present allowing for distinction between ASCCa and benign acantholytic processes such as pemphigus. PMID- 7774502 TI - Cytodiagnostic pitfalls in pulmonary coccidioidomycosis. AB - Two cases of pulmonary coccidioidomycosis which were initially misdiagnosed as carcinoma in cytologic examinations of material obtained by bronchoscopy or fine needle aspiration are reported. The cytodiagnostic pitfalls of misinterpreting reactive bronchial epithelial cells as carcinoma cells and of failing to recognize fungal organisms are discussed. PMID- 7774503 TI - Comparison of conventional and ThinPrep preparations of mucoid cytology samples. AB - Cytological specimens containing large amounts of mucus and/or blood are often a considerable problem as far as preparation and especially screening are concerned. The ThinPrep method, which uses a mucolytic and hemolysing solution and prepares slides automatically, eliminates difficulties in both areas. Comparing ThinPreps to conventionally prepared samples reveals equivalent or even superior cellular preservation. Cells are spread in a thin layer, mostly with only a minimal amount of residual mucus or blood. Screening is consequently much easier and faster. The time-saving effect does not compromise the diagnostic accuracy, as we could demonstrate with an 92% overall agreement in both procedures. The difference of 8% could possibly be attributed to inadequate splitting of the samples. PMID- 7774504 TI - The status of residency training in cytopathology. PMID- 7774505 TI - Cytological grading of breast carcinoma. PMID- 7774506 TI - Spindling artefact of urothelial cells. PMID- 7774507 TI - FNA lymphoproliferative diseases: myths and legends. PMID- 7774508 TI - Current management of acute myocardial infarction. AB - Acute myocardial infarction is a devastating cardiac clinical event, which is the result of progressive coronary arteriosclerosis. Coronary heart disease is a major health concern that accounts for a significant number of hospitalizations, health care expenditures, and deaths. Recent advancements in the nature and pathophysiology of progressive coronary disease and infarction have allowed us to curb the natural course of the disease, shorten hospital stays, and improve patient outcomes. Focused history taking and physical examination, with the assistance of the appropriate laboratory studies and an electrocardiogram, facilitate the rapid identification of a patient with myocardial infarction. Overall clinical results will be improved by minimizing the time from diagnosis to therapy. Several initial measures are readily available to the physician at the time of the patient's arrival in the hospital emergency room. Consideration regarding relief of pain, anticoagulation, and contraindications for thrombolytic therapy should accompany the initial evaluation. For patients in whom the diagnosis is in doubt, adjunctive confirmatory testing and imaging studies should be urgently sought. Elderly patients have a higher mortality rate from infarction, so an aggressive approach in this group of patients is warranted. Administration of thrombolytic therapy or primary angioplasty will be most efficacious in a majority of patients. The evolution of adjunctive medications will further improve efficacy and avoid reinfarction. Proper dosage and timing of adjunctive medications, along with dosage titration based on hemodynamic response, will facilitate the best possible results. Rapid restoration of flow down a suddenly occluded epicardial coronary vessel is the primary end point in therapy. With this in mind, there has been an increasing trend toward mechanical restoration of flow by means of primary angioplasty in centers where this technologic capability is available. Close attention to the patient's hemodynamic status along with rapid identification and therapy of peri-infarction arrhythmias will help to avoid clinical complications. When peripheral perfusion is compromised, hemodynamic monitoring, inotropic medications, and mechanical assistance may become necessary. Subsequent severe pump failure is usually the result of a devastating mechanical complication. Patients with mechanical complications have a high associated event-related mortality rate. Urgent identification of the nature of the complication with the use of invasive and noninvasive imaging studies, mechanical and inotropic assistance, and emergency surgical correction may be lifesaving.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774509 TI - Microelectronic systems for monitoring and enhancing patient compliance with medication regimens. PMID- 7774511 TI - Prospects for the use of antioxidant therapies. AB - Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural antioxidant defences have been found to be defective in many of the same diseases. This has led to suggestions that oxidative damage and therefore disease progression may be retarded by supplementing natural antioxidant defences. Potential antioxidant therapy includes natural antioxidant enzymes and vitamins or synthetic agents with antioxidant activity. Diseases where antioxidant therapy may be beneficial include diabetes mellitus, reperfusion injury, inflammatory diseases and the prevention of chronic processes such as atherosclerosis and carcinogenesis. Further well controlled prospective clinical trials of antioxidants are required to establish the efficacy and tolerability of antioxidant therapy in the treatment of human diseases. PMID- 7774512 TI - Current concepts and controversies in the use of vitamin K. AB - Vitamin K is a fat-soluble vitamin crucial to the production of many proteins involved with the coagulation process. It is integral in the synthesis of coagulants (factors II, VII, IX and X) and anticoagulants (proteins C and S). It is generally recognised that routine administration of vitamin K (phytomenadione) shortly after birth will prevent major neonatal morbidity and mortality related to haemorrhage. Vitamin K supplementation during pregnancy is also recommended if mothers are on anticonvulsant therapy or prolonged treatment with certain antibiotics. These medications, if ingested by pregnant women, predispose the neonate to a bleeding tendency caused by vitamin K deficiency. Vitamin K treatment of pregnant mothers before premature delivery has also been suggested to reduce the incidence of severe intracranial haemorrhage (ICH) in premature neonates. Although further studies are pending, the data to date do not support using antenatal vitamin K for preventing ICH. PMID- 7774510 TI - Panic disorder. Pathophysiology and drug treatment. AB - Advances over the past 2 decades in our understanding of the biology of panic disorder have paralleled a remarkable increase in the development of new pharmacological agents with antipanic effects. Although we can not presently use biological tests to help with our choice of therapeutic agent for individual patients, we can use this biological understanding in the development of overall pharmaco-therapeutic strategies. Current evidence does not support the hypothesis that panic disorder is associated with a primary disorder in one neurotransmitter system. Rather, the data suggest that the biological aetiology of panic disorder is related to abnormalities in the function of a variety of neurotransmitters including serotonin (5-hydroxytyrptamine; 5-HT), noradrenaline (norepinephrine), gamma-aminobutyric acid (GABA), dopamine, and cholecystokinin. It is likely, however, that panic disorder is a biologically heterogeneous condition and that biological subtypes may exist in which the primary abnormality may involve one or a few neurotransmitter systems. Currently, the data best support the hypothesis that pharmacotherapeutic agents with primary action at sites within the GABA and serotonin systems are the most effective in the treatment of panic disorder. Nevertheless, some patients will respond well to drugs with predominant activity in other systems, or may require pharmacotherapy designed to affect the function of more than 1 neurotransmitter. As our understanding of the biological aetiology of panic disorder evolves, the pharmacotherapeutic agents and strategies used in the treatment of this disorder will continue to evolve as well. PMID- 7774513 TI - Enoxaparin. A reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease. AB - Enoxaparin (enoxaparin sodium) is a low molecular weight derivative of unfractionated heparin which has been evaluated for the treatment and prevention of thromboembolic disease. Since a previous review in Drugs, well controlled clinical trials have confirmed the effectiveness of enoxaparin as prophylaxis in patients with a high risk for deep venous thrombosis (DVT), i.e. those undergoing hip or knee replacement surgery. Enoxaparin 30mg twice daily, initiated postoperatively, offers an overall balance of prophylactic efficacy and haemorrhagic tolerability which is superior to that of unfractionated heparin. In comparative clinical trials, this dosage demonstrated either improved efficacy and a similar haemorrhagic profile, or a similar degree of efficacy with a lower rate of haemorrhagic events, compared with unfractionated heparin 5000IU 3 times daily. Limited data indicate that an enoxaparin regimen of 40mg once daily, starting preoperatively, is more effective than unfractionated heparin in patients undergoing hip replacement and has a comparable haemorrhagic profile. In patients with a moderate risk for DVT, enoxaparin is similar to unfractionated heparin in both efficacy and haemorrhagic profile, while preliminary investigations have demonstrated the utility of enoxaparin in the prevention of DVT in elderly, nonsurgical patients. Enoxaparin may also be useful for the treatment of existing DVT and as an anticoagulant in haemodialysis. Thus, enoxaparin is an effective form of prophylaxis for thromboembolic disease in moderate to high risk surgical situations. Recent evidence for improved efficacy, together with a similar incidence of haemorrhagic complications in most situations, may lead to enoxaparin being preferred to unfractionated heparin for the routine prevention of DVT after high risk surgery. Although detailed comparisons with other low molecular weight heparins and antithrombotic agents are required before its relative clinical utility can be fully assessed, enoxaparin is likely to play a significant role in the prophylaxis of thromboembolic disorders. PMID- 7774514 TI - Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. AB - Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5 hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology. The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence of dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774517 TI - Diurnal variations of EEG power in healthy adults. AB - EEG power variations were evaluated in 9 healthy young adults from 8.45 a.m. to 9 p.m. and at 7 a.m. the next day. EEG signals were obtained from 16 electrodes in closed eyes and open eyes situations. Diurnal power variations were calculated for each frequency component, according to the recording situation (RS) and to the scalp site. Regarding values in the early morning on the first day, the power of almost all the frequency components showed an important diurnal increase. It came back close to initial values at 7 a.m. on the second day, which is in agreement with the existence of EEG circadian variations. Diurnal evolutions were dependent on the frequency components: the higher the frequency, the later was its diurnal maximum. For many frequency components, the diurnal variation was dependent on RS and the scalp topography. All these characteristics could be used to split the classical EEG bands, especially the delta and alpha bands and be useful for physiological and pharmacological research. PMID- 7774516 TI - Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. AB - Rifaximin is a derivative of rifamycin which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration; thus it is used primarily to treat local conditions within the gastrointestinal tract. In vitro data indicate rifaximin possesses good activity against species of Staphylococcus, Streptococcus and Enterococcus but lesser activity against species of Enterobacteriaceae. Bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. Results of comparative trials demonstrate that rifaximin is similar in efficacy to neomycin and lactulose in patients with hepatic encephalopathy and appears to be better tolerated. In 1 study, cyclical administration of rifaximin for 15 days per month was associated with progressive improvement over a 3-month period. In patients with infectious diarrhoea, rifaximin induces more rapid improvement in stool consistency and decreased frequency of faecal evacuations when compared with placebo, and is similar in efficacy to neomycin. Available data suggest rifaximin may be of some use in acute diverticulitis, but its use for the prevention of inflammatory complications or for control of common symptoms of diverticulosis requires further study. Preoperative treatment with rifaximin as antibacterial prophylaxis in colorectal surgery shows some potential but should be further investigated. Overall, rifaximin may be useful as an alternative therapy in hepatic encephalopathy but more data are needed to better define its clinical potential in infectious diarrhoea, diverticular disease and as antibacterial prophylaxis prior to colorectal surgery. PMID- 7774518 TI - EEG spectral analysis in vascular and Alzheimer dementia. AB - The role of EEG spectral analysis in the diagnosis of syndromes of dementia is still disputed. Since there have been few studies dealing with the profile of power spectra, the present investigation has focused on this aspect, constructing power spectra taken from 16 derivations and calculated by averaging twenty 2 sec epochs, using a serial array of frequencies from 1 to 32 Hz. The spectral analysis of the EEG, recorded under awake resting eyes closed (REC) and open (REO) conditions, was performed in 50 patients with Alzheimer's disease (AD), 37 with vascular dementia (VaD) and 36 elderly controls. Three spectral profiles were found under REC: (i) type A, showing a dominant 6.5-12 Hz peak (44% AD, 97.3% VaD), although lower than in controls; (ii) type B, lacking a dominant peak in the 6.5-12 Hz band, but characterised by high power in 1-6.5 Hz band (44% AD, 2.7% VaD); (iii) type C, corresponding to a flat, low voltage, spectrum (12% AD). Unlike controls, demented patients showed an increased REO/REC power ratio in the 6.5-12 Hz band, especially in those with type B spectra. AD patients with type B spectra had an earlier age of disease onset. PMID- 7774519 TI - Power spectrum and intracranial EEG patterns at seizure onset in partial epilepsy. AB - Intracranial electroencephalographic patterns of seizure onset during preoperative assessment with intracerebral and subdural electrodes have been correlated with surgical outcome in 15 patients with partial epilepsy assessed for surgery. The presence and topography of electrodecremental events, high frequency activity, irregular sharp waves intermixed with slow activity, spike wave activity and rhythmic ictal transformation at seizure onset were studied in a total of 78 complex partial seizures. Raw traces from intracerebral and subdural recordings were assessed visually in conjunction with changes in the following spectral variables (calculated for consecutive 1.28 sec epochs): amplitude (sum of amplitude of all components within a frequency band), activity, mobility, and complexity. The time course of these variables during preictal and ictal periods was displayed and assessed. This technique proved effective for detecting low-amplitude high-frequency activity and subtle electrodecremental events. It was concluded that: (a) most patients (12/15) showed early electrodecremental events, generalised or local, mainly involving frequencies below 40 Hz; (b) generalised electrodecremental events at onset did not imply poor outcome; (c) localised high-frequency activity, between 20 and 80 Hz, was associated with a good outcome. PMID- 7774515 TI - Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. AB - Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction. PMID- 7774520 TI - Propagation patterns of temporal spikes. AB - In standard EEG recordings, spikes appear as single events characterized mainly by the scalp location of the their peak voltage. The signal-to-noise ratio of raw EEG is usually too high to permit more detailed analysis. We used spike averaging to improve the resolution of interictal spikes in 40 patients with temporal lobe epilepsy. Spikes were identified visually in raw, digitally stored EEG. When multiple spike types were present in a patient, they were grouped separately. Spikes were synchronized for averaging by aligning their negative peaks in a designated channel. Sixteen patients demonstrated spike propagation from anterior temporal to posterior temporal electrode locations. Thirty-six patients demonstrated spread of spikes from anterior temporal to fronto-polar electrode sites. While anterior temporal and fronto-polar spikes were often synchronous, fronto-polar spikes followed anterior temporal discharges in 25% of cases and preceded them in 13%. Spike averaging revealed propagation patterns not apparent on visual inspection of raw EEG. We speculate that these patterns may reflect inherent physiological properties of temporal and frontal neuronal circuits, possibly utilized by the epileptogenic process. PMID- 7774521 TI - Topographic EEG changes due to hypobaric hypoxia at simulated high altitude. AB - Multichannel human EEG signals were studied topographically in subjects exposed to an atmosphere of reduced air pressure in a chamber in which high-altitude conditions were simulated. EEG signals from 16 electrodes placed on the scalp were recorded simultaneously with electrocardiography and vertical eye movement. Baseline records were first obtained at sea level (PRE 0 m), and then at reduced air pressures corresponding to the altitudes of 3000 m, 4000 m, and 6000 m, respectively, and after returning to sea level (POST 0 m). A complete set of EEG records under all 6 conditions was obtained in 5 of the 15 subjects, and under 5 conditions (all except the 6000 m condition) in 3 other subjects. The spectral powers of 1 min epochs of the multichannel EEG signal under each altitude condition were compared to that at PRE 0 m using analysis of variance. Under the 3000 m condition, the spectral power of the 10-11 Hz components was significantly decreased and, with increasing altitude, significant decrease of spectral power was observed in a wider range of the alpha frequency band. Under the 6000 m condition, the decrease of spectral power of the alpha band in the posterior brain areas was -7 dB compared to the baseline. In contrast, the spectral power of the theta frequency band in anterior brain areas increased significantly in the 5000 m and 6000 m conditions. At the POST 0 m condition after return from the 5000 m condition (without exposure to the 6000 m condition), the EEG showed recovery to the level of the baseline PRE 0 m condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774522 TI - Electrocortical distinction of vocabulary types. AB - Psycholinguistic theories propose that words of the 2 major vocabulary classes, content (open-class) and function (closed-class) words, are computationally distinct and have different neuronal generators. This predicts distinct EEG patterns elicited by words of these 2 classes. To test this prediction, content and function words, together with matched pseudowords, were presented in a lexical decision task (where subjects had to decide whether stimuli were meaningful words or not). Evoked potentials were recorded from 17 electrodes 12 of which were located in close vicinity of the perisylvian cortices. Already 160 msec post stimulus onset, substantial differences in activity patterns distinguish the 2 vocabulary classes. A hemisphere by word class interaction revealed interhemispheric differences for function words but not for content words. Potentials evoked by function words were more negative over the left hemisphere compared to the right. These results evidence that brain mechanisms underlying function and content word processing are different. The following explanation of the data is proposed: content words correspond to neuronal assemblies equally distributed over both hemispheres, while assemblies corresponding to function words are strongly lateralized to the left hemisphere and primarily located in the perisylvian region. PMID- 7774524 TI - Discrimination between phase-locked and non-phase-locked event-related EEG activity. AB - Differentiation between phase-locked and non-phase-locked event-related EEG activity is an important task in the evaluation of event-related EEG activity. Event-related changes of EEG activity such as event-related desynchronization (ERD) or event-related synchronization (ERS) can be quantified by either instantaneous band power or intertrial variance calculations. In the former case the ERD or ERS can be masked by an event-related potential while in the latter it is not. Examples from sensory stimulation and movement experiments, where the ERD (ERS) is calculated by both methods, are shown and discussed. PMID- 7774523 TI - A spatial oculomotor memory-task performance produces a task-related slow shift in human electroencephalography. AB - Electroencephalographic (EEG) deflections in humans related to the performance of memory-guided saccades were studied in this work. The EEG deflections were recorded during 2 spatial oculomotor delayed response tasks in which the subject was instructed to make a saccade either to the right or to the left depending on the spatial location of the cue which had been shown in the beginning of the delay period. The EEG deflections were compared to those recorded during a control task in which the subject also made a saccade to the right or to the left after a delay but the requirement to keep spatial information actively in mind was minimized. A slow delay-related shift was recorded during all task conditions. The slow shift was positive in the most frontal and negative in the more posterior recording sites. The negative slow shift in the more posterior recording sites was larger in the memory tasks than in the control task. Since the memory and the control tasks differed mainly in their requirement to hold spatial information in mind it is suggested that the difference in the magnitude of slow shifts between the memory and the control tasks reflects neural activity related to spatial working memory. But although the oculomotor responses in all tasks were similar, the preparatory activities for the impending eye movements may not have been similar and in addition to working memory may have contributed to the observed differences in the slow shifts. PMID- 7774525 TI - Virus-induced increases in airway mast cells in brown Norway rats are associated with enhanced pulmonary viral replication and persisting lymphocytic infiltration. AB - Brown Norway (BN) rats are more susceptible than Fischer 344 (F344) rats to parainfluenza virus-induced lung injury and to bronchiolar mast cell increases that are associated with persistent airway hyperresponsiveness. In this study, pulmonary viral replication as well as immune, inflammatory, and airway mast cell responses to Sendai virus infection were compared between neonatal BN and F344 rats. BN rats supported prolonged viral replication, and viral titers in BN rats were 5-fold higher (p < .05) than in F344 rats at 7 days after inoculation. F344 rats had 18-fold higher (p < .06) numbers of lymphocytes in bronchoalveolar lavage fluid at 7 days after inoculation than did BN rats. Persisting bronchiolar aggregates of lymphocytes, plasma cells, and macrophages were more common, and increases in bronchiolar mast cells were greater in BN rats than in F344 rats. No strain differences were detected in bronchiolar intramural infiltrates of CD4 + or CD8 + cells. The greater susceptibility of BN rats to virus-induced increases in bronchiolar mast cells and airway responsiveness may be the result of their less efficient viral clearance mechanisms and more persistent bronchiole-centered inflammatory response. PMID- 7774526 TI - Hydrogen peroxide inhibits lung neutral endopeptidase. AB - Oxidants have been implicated in the pathogenesis of many inflammatory airway diseases. Neutral endopeptidase (also called enkephalinase, EC 3.4.24.11) is a peptidase that is involved in the degradation of several proinflammatory peptides, such as tachykinins and kinins. Indirect evidence suggests that airway neutral endopeptidase is inactivated by oxidants. To determine whether hydrogen peroxide inactivates neutral endopeptidase, we studied the activity of this peptidase in washed crude preparations of membranes from guinea pig lungs. Washed crude membrane preparations were exposed to increasing concentrations of hydrogen peroxide (1.25-25 mM) in the presence or absence of two different concentrations of catalase (300 and 700 U/mL). Neutral endopeptidase activity was inhibited by hydrogen peroxide in a concentration-dependent fashion (p = .0001). Addition of catalase prevented, in a concentration-dependent fashion, the inhibition of neutral endopeptidase induced by hydrogen peroxide (p = .0001). Mannitol (40 mM) and L-methionine (20 mM) did not prevent inhibition of neutral endopeptidase induced by hydrogen peroxide (2.5 mM). It can be concluded that neutral endopeptidase is inactivated by hydrogen peroxide, an effect that is prevented by catalase. Hydrogen peroxide-induced inactivation of neutral endopeptidase is not mediated by spontaneous generation of either hydroxyl radical or hypochlorous acid in the membrane preparation. Our results suggest that neutral endopeptidase inactivation may occur in airway diseases associated with exposure to or production of oxidants. PMID- 7774527 TI - Effect of IL-1 blockade on inflammatory manifestations of acute ventilator induced lung injury in a rabbit model. AB - Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL 1, plays a role in this process, a rabbit model of ventilator-induced injury was created. Animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL/kg of saline and then ventilated for 8 h with either FIO2 0.21 and normal pressures or FIO2 1.0 and high ventilator pressures. The animals exposed to hyperoxia/hyperventilation demonstrated a greater increase in lung lavage neutrophil counts and a higher histological injury score, as well as a faster decline in oxygenation compared to the control animals. A third group of rabbits received 800 micrograms of recombinant IL-1 receptor antagonist after lung lavage and prior to the exposure to FIO2 1.0 and high ventilator pressures. These animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8-h ventilatory period compared to hyperoxia/hyperventilation rabbits. IL-1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline treated hyperoxic/hyperventilated rabbits. IL-1 is a mediator of acute inflammation due to ventilator-induced lung injury. PMID- 7774528 TI - Emphysema as a result of involuntary exposure to tobacco smoke: morphometrical study of the rat. AB - Several attempts have been made to describe the relation that exists between tobacco smoke and emphysema, through different experimental models of the active smoker. Despite the negative effects that involuntarily inhaled tobacco smoke can have on the lung, no experimental model of the passive smoker has been proposed. In this study, an experimental model of the involuntary smoker is described and the following hypothesis proposed: Passive exposure to tobacco smoke produces morphological alterations in the rat lung, which are compatible with emphysema. Emphysema will be considered to have been caused when enlargement of the distal airspaces of the lung and lung tissue destruction are demonstrated. Sixty Wistar rats were used, divided into two groups: a control group and a group that was passively exposed to tobacco smoke for a period of 3 months. A morphometrical study of the lung was performed using a computerized system. To demonstrate enlargement of the distal airspaces of the lung, the following variables were quantified: alveolar chord and mean linear intercept index (Lm); tissue loss was demonstrated by means of the quantification of the variables: tissue density, internal alveolar perimeter (IAP), and wall thickness (WT). The elastic fiber was also quantified. The animals that were exposed to tobacco smoke displayed the following significant alterations (p < .05): an increase of the alveolar chord and of the Lm, a decrease of the IAP, WT, and tissue density, and a loss of the elastic component of the lung. On the basis of these findings, it is concluded that the rats that were exposed in a passive way to tobacco smoke display morphological pulmonary alterations that are compatible with the definition of emphysema. PMID- 7774529 TI - Urinary excretion of polyamines in the adult respiratory distress syndrome. AB - Polyamines are low molecular weight polycations that are critically important in cellular proliferation and differentiation. To investigate their potential role in acute lung injury, the polyamines spermidine, spermine, and putrescine were measured in 24-h urine collections from intubated patients with ARDS (n = 12) or congestive heart failure with cardiogenic pulmonary edema (CHF, n = 10) and in normal subjects (n = 10). Mean concentrations of putrescine were similar between groups, but spermidine concentrations in patients with ARDS (52.7 +/- 19.7 nmol/mg creatinine) were significantly higher than in normal subjects (4.9 +/- 0.7 nmol/mg), p < .05. Mean concentrations of spermine in ARDS (270.6 +/- 78.1 nmol/mg) were higher than in CHF (1.0 +/- 0.5 nmol/mg), p < .05, and normal subjects (0.3 +/- 0.1 nmol/mg), p < .05. Concentrations of putrescine increased significantly during the first 7 days of ARDS (241.5 +/- 127.1% above baseline, n = 6), p < .05. Urinary polyamine excretion did not correlate with severity of gas exchange or death. These results are the first to suggest a potential role for polyamines in the pathophysiology of ARDS. PMID- 7774530 TI - Identification of IL-1 inhibitory activity as IL-1 receptor antagonist (IL-1ra) in vitro and kinetics of IL-1ra and IL-1 beta in experimental rabbit lung granuloma. AB - This study investigated whether interleukin-1 (IL-1) inhibitory activity in LPS stimulated culture supernatants of alveolar macrophages and epithelioid cells obtained from rabbit lung granulomas induced by complete Freund's adjuvant (CFA) was identical to IL-1 receptor antagonist (IL-1ra) and examined the changes of IL 1ra and IL-1 beta levels in lung tissue during the natural course of granulomatous inflammation. In the thymocyte proliferation assay, prostaglandin E2 (PGE2)-free culture supernatants from each cell population revealed a bell shaped IL-1 titration curve with IL-1 activity suppressed at dilutions of 1:1 to 1:2, and gel chromatography of serum-free culture supernatants showed an IL-1 inhibitory peak at 21-25 kD. Suppression of IL-1 activity in the supernatants at lower dilutions and the gel-purified IL-1 inhibitory activity both almost disappeared after IL-1ra depletion with an anti-rabbit IL-1ra immunoaffinity column, indicating that IL-1ra was responsible for this in vitro IL-1 inhibitory activity. Pulmonary tissue levels of IL-1 beta pecked at 24 h (52.0 +/- 9.5 pg/mg) after CFA injection, whereas IL-1ra levels peaked at 4 weeks (23.1 +/- 4.0 ng/mg) when granuloma development was maximal, and the molar excess of IL-1ra to IL-1 beta peaked from 4 weeks onward at over 800-fold. These observations suggest that IL-1ra may be effective for IL-1 regulation, especially in the later stage of granulomatous responses. Immunohistochemical studies demonstrated that the cellular source of IL-1ra within the pulmonary granulomas was mainly epithelioid cells. PMID- 7774531 TI - Exercise potentiation of lung injury following inhalation of a pneumoedematogenic gas: perfluoroisobutylene. AB - Exercise performed after exposure to various pneumoedematogenic gases can increase the severity of pulmonary edema beyond that which occurs when exposure is followed by rest. The present study was performed to investigate the potential relationship between a preexisting breach in the lung's permeability status following exposure to an edematogenic gas (perfluoroisobutylene, PFIB) and the potentiating effects of postexposure exercise. Rats were exposed to a concentration of PFIB (100 mg/M3 for 10 min) that results in a unique postexposure latency period (approximately 8 h) prior to the occurrence of overt pulmonary edema. The study examined how exercise performed during and after the latency period affects the severity of the injurious response to this toxic gas. The initial results indicated that exercise performed during the post-PFIB exposure latency period does not potentiate the injurious response, as judged by conventional lung gravimetric and histopathological criteria, but when overt pulmonary edema was preexistent, exercise had a potentiating effect. Changes in lavageable protein were assessed as a more sensitive indicator of permeability changes that may occur during the latency period following PFIB exposure, and the study examined how exercise performed early during the latency period affects this index of pulmonary edema. The study also assessed whether PFIB-induced damage to lung cells is enhanced by exercise during the latency period by measuring lavageable lactate dehydrogenase activity. The results from these latter experiments suggest that a preexisting enhancement in lung permeability is not an absolute requirement for exercise to potentiate the pulmonary edematous response in lungs that are undergoing insidious injury, and that postexposure exercise does not enhance the cell-killing effects of PFIB as a mechanism underlying the exercise potentiating response. Conceivably, the ability of exercise to increase lavageable protein in the absence of a preexisting increase in lung permeability may be due to hyperventilation- and/or pulmonary hypertension-associated intercellular junctional changes that may occur during exercise. Additionally, it remains possible that exercise during PFIB-induced insideous lung injury results in an enhancement in the rate of transcellular transport of blood proteins onto the alveolar surface. PMID- 7774532 TI - Beta-carotene, vitamin E and vitamin C in different stages of experimental carcinogenesis. PMID- 7774533 TI - Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function. AB - OBJECTIVE: To compare the effects of supplementing a low fat diet with an alpha linolenic acid-rich (C18:3 n-3) oil with a linoleic acid-rich (C18:2 n-6) oil on platelet composition and function. DESIGN: Prospective study with random allocation to one of the two oils. SETTING: Free-living study. SUBJECTS: Eleven healthy young males recruited from within the University. INTERVENTIONS: Subjects were allocated to consume 40 g of either flaxseed oil (n = 5) or sunflowerseed oil (n = 6) daily for 23 days. Fasting blood samples were collected at commencement and completion of supplementation for analysis of platelet fatty acids and platelet aggregation. RESULTS: The platelet eicosapentaenoic acid (EPA) more than doubled in the group taking flaxseed oil (P < 0.05) but was unchanged in the sunflowerseed group. As a result the platelet EPA:arachidonic acid ratio, considered a marker for thromboxane production and platelet aggregation potential, increased in the flaxseed group (P < 0.05). The aggregation response induced by 0.75 and 2 micrograms of collagen was decreased in those taking flaxseed oil (P < 0.05). CONCLUSION: This study provides further evidence that consumption of alpha-linolenic acid-rich oils may offer protective effects against cardiovascular disease over linoleic acid-rich oils via their ability to decrease the tendency of platelets to aggregate. PMID- 7774534 TI - Infant feeding and nutritional status: the dilemma of mothers in rural Senegal. AB - OBJECTIVE: To describe infant feeding practices in rural Senegal in relation to age and nutritional status. The main hypothesis to be tested was whether mothers modulate feeding in response to growth and nutritional status of their infants. DESIGN: A cross-sectional survey using qualitative 24-h recalls and lifetime recalls to assess feeding practices, and using weight and recumbent length measurements to assess nutritional status. SETTING: Three health clinics in the Fatick region, a rural area of Senegal, West Africa, covering a population of 26,600. SUBJECTS: All 2-10-month-old infants attending four immunization sessions in 1991 (n = 1174; 80% of convoked infants). MAIN OUTCOME MEASURES: Prevalence of feeding with additional food (gruel, family diet and food of animal origin), weight-for-length and length-for-age. RESULTS: All infants were breastfed. A supplement had been given the day before the survey to 10% of infants aged 2-3.9 months, 30% of infants aged 4-5.9 months and 45% of those aged 6-6.9 months. The main food items were watery millet gruel and family diet (millet or rice). Gruel was given in response to perceived breast-milk insufficiency. Animal products were seldom eaten at any age. Length-for-age and weight-for-length were significantly lower among infants supplemented with millet gruel, when adjusted for age; while no such relationship was found with family diet. CONCLUSION: Mothers preferentially fed gruel to small, thin infants. PMID- 7774535 TI - Metabolic responses to starch in oat and wheat products. On the importance of food structure, incomplete gelatinization or presence of viscous dietary fibre. AB - OBJECTIVE: Evaluate the importance of incomplete gelatinization, food structure and presence of viscous dietary fibre for the postprandial glycaemic and insulinaemic responses to oat and wheat products. DESIGN: Three common breakfast meals were tested, 'raw' rolled oats (muesli), boiled rolled oats (oat porridge) and white wheat bread. Boiled intact oat and wheat kernels (kernel porridges) were also included. For comparison, glycaemic indices (GIs) were calculated both from analysis of capillary and venous blood samples. SETTING: The study was performed at the research laboratory, Dalby Health Sciences Centre (primary care). SUBJECTS: Nine healthy male volunteers between 65 and 70 years of age participated in the study. RESULTS: The rolled oats and oat porridge elicited high metabolic responses. No differences in the glycaemic and insulinaemic indices (IIs) were seen between these products and white wheat bread. In contrast, the kernel porridges produced low glucose and insulin responses. No differences were obtained in GI values whether based on capillary or venous blood. However, with some products capillary blood allowed smaller differences to be detected. CONCLUSIONS: Neither incomplete gelatinization in rolled oats nor naturally occurring viscous dietary fibre in oats affect postprandial glycaemia, whereas enclosure of intact kernels significantly blunt metabolic responses. PMID- 7774536 TI - Iron balance in menstruating women. AB - OBJECTIVES: To study factors determining iron balance in menstruating women by examining the relationships between total iron requirements, based on menstrual iron losses and basal iron losses, and serum ferritin concentration, transferrin saturation, blood haemoglobin concentration, bone marrow haemosiderin and absorption of iron from a test dose of ferrous sulphate (0.56 mg Fe). SUBJECTS: The study was made in 203 women all aged 38 years, randomly selected from the census register of Goteborg. The study was originally made in 1968-69. Serum ferritin in frozen sera was first analysed in 1978. Reanalyses, calibrated to the International Standard 80/602, and studies on the effect of storage of sera, were made in 1992. This allowed a complete re-examination of the importance of different determinants of iron balance in women. RESULTS: With increasing iron requirements there was an increase in iron absorption, and a decrease in serum ferritin concentration and transferrin saturation. Above a certain level of iron requirement there was a rather sudden decrease in haemoglobin concentration and in stainable iron in bone marrow smears, indicating the critical level of iron requirements in these women that could be balanced by an increased iron absorption from the present diet. This level represents the maximal adaptation to maintain iron balance in an iron-replete state that can be achieved with this diet and corresponds to a prevalence of iron deficiency of about 25%. CONCLUSIONS: The continuous regulation of iron absorption from iron deficiency to iron repletion has a critical balance point determined by the properties of the diet. PMID- 7774538 TI - Is dietary underreporting macronutrient specific? PMID- 7774537 TI - Diet and vitamin D status among pregnant Pakistani women in Oslo. AB - OBJECTIVES: In the present study the diet and the nutritional status of pregnant Pakistani immigrant women have been compared with a group of Norwegian women. DESIGN: A cross-sectional survey of women in the 18th week of pregnancy. SETTING: Women referred to routine ultrasound examination at Aker and Ulleval Hospitals in Norway. SUBJECTS: All (58) healthy women of Pakistani origin referred from October of 1991 to January of 1992 were included, of whom 38 (66%) participated. Forty-five Norwegian women were randomly included in the same period and 38 (84%) of these women participated. RESULTS: The serum levels of 25-hydroxyvitamin D3 were significantly lower in the Pakistanis compared with the Norwegians (median 19 nmol/l vs 55 nmol/l, P < 0.001) and 83% of the Pakistani women had 25 hydroxyvitamin D3 levels below the reference value (< 30 nmol/l). The Pakistanis had higher levels of serum parathyroid hormone (median 2.6 vs 1.6 pmol/l, P < 0.001). The Pakistanis also had a lower dietary intake of vitamin D than that of the Norwegians (median 2.2 vs 3.3 micrograms/day, P < 0.05), and a lower total intake, including supplements (median 2.9 vs 7.0 micrograms/day, P < 0.001). Among the Pakistanis a correlation was found between the dietary intake of margarine, the main source of vitamin D in the diet, and the concentration of 25 hydroxyvitamin D3 in serum, r = 0.48 (P = 0.01). In general, the Pakistanis avoided any direct sunshine exposure, and no relation between outdoor activity and serum level of 25-hydroxyvitamin D3 was found. The Pakistani women had a lower intake of calcium than the Norwegians (median 793 vs 1134 mg/day, P < 0.001). CONCLUSION: This study has shown that Pakistani women living in Oslo are at great risk of developing vitamin D deficiency during pregnancy. The main reasons for this are avoidance of sun exposure, a low dietary intake of vitamin D, and no or little use of supplementation. PMID- 7774539 TI - Serum cholesterol and ischaemic heart disease. PMID- 7774540 TI - Infection of horses by Tyzzer's bacillus. PMID- 7774542 TI - Vertical tears of the cranial horn of the meniscus and its cranial ligament in the equine femorotibial joint: 7 cases and their treatment by arthroscopic surgery. AB - Five horses with a vertical tear in the cranial horn and cranial ligament of the medial meniscus and 2 horses with a similar injury in the lateral meniscus were diagnosed from a series of 126 horses which were examined arthroscopically for stifle lameness. All the lesions had similar characteristics. The tear was about 1 cm from the axial border of the meniscus and its ligament and, in all but one case in which it was incomplete, much of the torn tissue was loosely attached in the axial part of the joint from where it was removed. The remaining meniscus, abaxial to the tear, was displaced cranially and abaxially and its torn edges were debrided. Radiographically, 6 cases had proliferative new bone on the cranial aspect of the intercondylar eminence of the tibia and 3 had calcified soft tissue densities in the cranial, medial or lateral femorotibial joint. Following surgery and a 6 month period of rest and controlled exercise, 3 horses returned to full competition work, one was usable for hacking, 2 are convalescing and one is lame after one year. It is postulated that this could be a characteristic meniscal injury in horses which can benefit from arthroscopic surgery. Better techniques for accessing the body and caudal pole of the menisci are needed if a more complete diagnosis and treatment of meniscal injuries are to be achieved. PMID- 7774541 TI - Absorption and dosage of theophylline in the horse after single and repeated administration of a microencapsulated preparation. AB - The kinetics of 2 formulations of theophylline were studied in horses. In an initial cross-over study (Phase I) serum concentration-time curves were determined for granulated and microencapsulated theophylline after a single oral administration (5 mg/kg bwt). In Phase II microencapsulated theophylline was administered at 5 mg/kg bwt/12 h for 10 days at feeding time, as in normal clinical practice. Although no significant differences between the 2 preparations were found with respect to the main kinetic parameters, the microencapsulated form was more evenly and completely absorbed from the digestive tract; furthermore, after the repeated treatment, its trough-peak serum concentrations were always within the therapeutic window and no toxic effects were observed in treated animals. PMID- 7774544 TI - How the horse moves: 1. Significance of graphical representations of equine forelimb kinematics. AB - The kinematics of 24 two-year-old Dutch Warmblood horses were recorded at the trot (4 m/s) on a high-speed treadmill to study the coordination of joints within the equine forelimb. Joint angle-time, angle-angle, stick, and marker diagrams were used to show forelimb motion graphically. Because the kinematic data referred to the joint angles of the horse standing squarely and were time standardised to the duration of the stride cycle, mean joint curves could be calculated for the total group. The motion of each segment in the equine forelimb during a complete stride is described and its function in intralimb coordination evaluated. It appeared that the rotation of the scapula and the cranio-caudal movement of the distal forelimb are synchronous and pendular. The carpal joint rapidly snaps into overextension at the beginning of the stance phase to enable the forelimb to work as a propulsive strut. The fetlock joint acts as an elastic spring, thereby conserving energy and, at the same time, absorbs oscillations generated by initial ground contact. Furthermore, the coordination between carpal and fetlock joints in the swing phase appears to be strongly influenced by inertia. Using the graphic tools evaluated in this paper, we were able to visualise the kinematics of the equine forelimb and relate these to specific functions of the forelimb in locomotion. This information can be used to select kinematic variables for clinical studies in which equine forelimb function has to be described and quantified. PMID- 7774543 TI - Effect of feeding state on the response of horses to repeated bouts of intense exercise. AB - Four mature Standardbred horses were used in a 2-period cross-over design experiment to evaluate the effect of feeding state (fed or fasted) on metabolic response to 2 repeated bouts of exercise. Horses were either fasted 15 to 16 h before exercise or fasted for 12 h and then fed 2 kg of whole corn 2.5 to 3 h before exercise. In the first period, 2 horses in each feeding state were exercised. In the second period, the treatments were switched. The exercise test consisted of 2 exercise bouts separated by a 90 min recovery period. Each exercise bout included a warm-up phase and a high intensity phase (1600 m at 11 m/s on a 2% graded treadmill). Blood samples collected during the exercise test were analysed for glucose, non-esterified fatty acids (NEFA), insulin and lactate concentrations. Fasted horses had lower insulin concentrations and higher NEFA concentrations at the onset of exercise (P < 0.05). NEFA concentrations were consistently higher (P < 0.05) in the fasted horses until the high intensity phase of the second exercise bout. Feeding state did not affect heart rate or plasma lactate responses to exercise. Plasma glucose concentrations tended to decline in the fed horses during the first exercise bout. Neither a positive nor a negative effect of feeding state on horses performing repeated bouts of intense exercise were found. PMID- 7774545 TI - How the horse moves: 2. Significance of graphical representations of equine hind limb kinematics. AB - Kinematic data of the equine hind limb are presented graphically and related to functional aspects of the hind limb in locomotion. The trot of 24 two-year-old Dutch Warmblood horses was recorded at 4 m/s on a high-speed treadmill using kinematic analysis equipment. Joint angle-time, angle-angle, stick and marker diagrams were used to present graphically the data following standardised procedures. As the kinematic data were expressed with reference to the joint angles of the horse standing squarely and were time-standardised to the duration of the stride cycle, mean joint curves for the total group could be calculated and therefore describe the function of the different segments of the equine hind limb. The motion of the hind limb in the sagittal plane appeared to be pendular around a rotation point in the acetabulum. During the stance phase the extension of the fetlock joint and stance flexion of the stifle, tarsal and coffin joints illustrate the shock absorption of the hind limb. In the swing phase the reciprocal apparatus, which forms the coupling mechanism between stifle and tarsal joint, also influences the fetlock joint because synchronous flexion and extension between these 3 joints were demonstrated. By graphically presenting hind limb motion we were able to illustrate the relation between kinematics and function. This graphic analysis can be used in clinical studies involving quantification of equine hind limb coordination in the sagittal plane. PMID- 7774546 TI - Interstitial pneumonia in the horse: a fledgling morphological entity with mysterious causes. PMID- 7774547 TI - Autologous blood instillation alters respiratory mechanics in horses. AB - To investigate physiological consequences of autologous blood instillation in the lungs of healthy horses, respiratory mechanics and bronchial response to histamine were studied in 8 Thoroughbreds before and after introducing autologous blood (n = 5) and sterile saline solution (n = 3) into their lungs. Blood instillation resulted in a decrease in dynamic compliance (Cdyn) and increased respiratory resistance (R). Bronchial sensitivity and reactivity were unchanged after blood introduction. There were no significant changes in pulmonary mechanics or bronchial response after saline instillation. PMID- 7774548 TI - Effects of a 3 month endurance training programme on skeletal muscle histochemistry in Andalusian, Arabian and Anglo-Arabian horses. AB - Twenty adult (5 to 14 years old) sedentary stallions of several breeds (8 Andalusians, 7 Arabians and 5 Anglo-Arabians) were endurance-trained for 3 months. Duplicate biopsies from 2 different depths (20 mm, superficial sampling site; 60 mm, deep sampling site) of the gluteus medius muscle were collected before and after training and after 3 months of detraining. Few significant changes in muscle fibre type composition were recorded in response to training. The percentage of type I fibres in the deep sampling site of the muscle in Andalusian horses and of type IIB oxidative fibres in the superficial region in Anglo-Arabians had increased significantly (P < 0.05) after training. The mean type I and IIA cross-sectional area was increased significantly (range P < 0.05 to P < 0.01) after 3 months' training in the deep site of the muscle in Arabian and Andalusian horses, but not in Anglo-Arabians. The changes seen in fibre sizes disappeared after the detraining period. The mean number of capillaries adjacent to type I fibres in the superficial sampling site of the muscle had increased significantly (P < 0.05) in response to training in Andalusian and Arabian horses. However, a significant decrease in the mean number of capillaries in contact with each fibre type relative to the mean area of that fibre type was observed associated with training in the deep region of the muscle for type I and IIA fibres in Arabians (P < 0.01) and for type I fibres in Andalusian horses (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774549 TI - Meniscus lesions in man and horse. PMID- 7774550 TI - Sensory innervation of the navicular bone and bursa in the foal. AB - The sensory innervation of the navicular bone (os sesamoideum distale) and its suspensory ligaments [ligamenta sesamoidea collateralia (CSL) and ligamentum sesamoideum distale impar or distal sesamoidean impar (DS-impar) ligament] and the navicular bursa (podotrochlearis) was examined in the neonatal foal using immunocytochemistry. With antisera raised to substance P (SP) and human calcitonin gene-related peptide (CGRP), immunoreactive nerves were demonstrated to innervate the CSL and navicular bursa. Within CSL, and SP- and CGRP-like nerves were present in the synovial lining of the navicular bursa, appearing to reach the surface lining. These nerves appeared to enter the CSL and navicular bursa via the abaxial regions of the foot. Both peptides were present in the deep digital flexor tendon (DDf) along the palmar border of the navicular bursa, as well as in the DS-impar ligament. More nerve fibres were present in the dorsal part of CSL bordering the distal interphalangeal joint than was observed palmarly in CSL along the navicular bursa. Both peptides were observed to innervate the cartilage canals within the navicular bone. In terms of relative densities of immunoreactive SP- and CGRP-like peptides, the CSL dorsally and the DS-impar ligament had the highest relative densities of nerve fibres followed by the navicular bone, the palmar aspect of CSL and the DDf tendon bordering the navicular bursa. These results are discussed in relationship to local anaesthetic injections into the navicular bursa. PMID- 7774551 TI - Haematuria, pigmenturia and proteinuria in exercising horses. AB - The effects of exercise on urinary excretion of red blood cells, pigments (haemoglobin and myoglobin) and protein were studied in 8 mares performing treadmill exercise at speeds eliciting 40, 60 and 95% of the maximal oxygen consumption (VO2max). Gross haematuria and pigmenturia were observed in all horses during exercise at the 2 higher intensities, while these findings were detected in only one of 8 mares during exercise at 40% of the VO2max. For the remaining 7 mares exercised at 40% of the VO2max, increased urinary excretion of red blood cells (RBCs) and pigments was evident after centrifugation of urine samples and reagent strip analysis of the supernatant fractions. An increase in urine flow (UF) during exercise at 40% of the VO2max may have contributed to the infrequent observation of gross haematuria and pigmenturia during exercise at this intensity. A transient increase in UF following exercise at 60 and 95% of the VO2max resulted in rapid resolution of gross haematuria and pigmenturia, but increased urinary excretion of RBCs and pigments remained evident by reagent strip analysis for up to 60 min following exercise. Mean +/- s.e. urinary protein excretion increased from a resting value of 2.2 +/- 0.2 mg/min to 5.6 +/- 0.9, 14.5 +/- 4.7 and 78.4 +/- 18.6 mg/min after exercise at 40, 60 and 95% of the VO2max, respectively. These results demonstrate that exercise induced haematuria and pigmenturia and post exercise proteinuria are common in horses. Their occurrence is transient and does not appear to be associated with any lasting changes in renal function. PMID- 7774552 TI - The effect of maternal age and parity on the racing performance of thoroughbred horses. PMID- 7774553 TI - Diffuse alveolar damage in the horse. PMID- 7774554 TI - Seroanalysis of Tyzzer's disease in horses: implications that multiple strains can infect Equidae. AB - A monoclonal antibody based competitive inhibition assay was used to detect antibodies in horse sera to purified flagellar antigens from distinct Clostridium piliforme isolates. Sequential absorption of hyperimmune rat serum to C. piliforme isolate E (horse-origin isolate), a positive C. piliforme-immune horse serum, and other suspected immune horse sera with unrelated bacteria or C. piliforme isolates E or isolate R1 (rat-origin isolate) alone demonstrated the specificity of this assay for C. piliforme. This specificity was associated with the inhibition of monoclonal antibody binding to C. piliforme flagella, rather than to C. piliforme somatic antigens, by horse immunoglobulins partially purified from serum. Thirty seven of 162 horse sera possessed large amounts of antibody to the flagella of C. piliforme isolate E and 23 of the 162 had large amounts of antibody to the flagella of C. piliforme isolate R1; 9 of the sera possessed large amounts of antibody to both flagellar antigens. Absorption of these sera with isolate E or R1 demonstrated that antibody reactivity to the 2 C. piliforme isolates was isolate-specific and not due to antibody cross-reactive with both isolates. These results suggest that infection of horses with C. piliforme may be relatively common; and that they are susceptible to at least 2 distinct strains. PMID- 7774555 TI - One-dimensional genome scanning: identification of the basis of a mouse mutation and identification of genomic changes in ovarian carcinoma. AB - We have developed a simple one-dimensional electrophoretic method, genome scanning, that can be used to identify large-scale genomic differences between two or more DNA samples. Genome scanning is especially useful in the detection of genetic amplifications, deletions, and rearrangements. The assay is essentially a high-resolution Southern analysis, comparing equivalent amounts of genomic DNA samples that are variant for a given trait. The Southern blots are hybridized to a probe sequence derived from a medium copy number repetitive element (1000-2000 copies per haploid genome) naturally dispersed throughout the genome. The hybridization pattern that results is complex and consists of hundreds of bands. If the DNA samples are otherwise equivalent, a net difference in hybridization intensity between homologous bands of different samples indicates a genetic change. In this report, we discuss the origin of the method, its premise, and review its application to mouse mutational analysis and to human cancer research (a more detailed discussion of the theory is presented elsewhere in this issue; Y. Gondo and M. H. Brilliant, Electrophoresis 1995, 16, 174-178). PMID- 7774556 TI - Size-selected genomic libraries: the distribution and size-fractionation of restricted genomic DNA fragments by gel electrophoresis. AB - By using one-dimensional genome scanning, it is possible to directly identify the restricted genomic DNA fragment that reflects the site of genetic change. The subsequent strategies to obtain the molecular clones of the corresponding restriction fragment are usually as follows: (i) the restriction of a mass quantity of an appropriate genomic DNA, (ii) the size-fractionation of the restricted DNA on a preparative electrophoresis gel in order to enrich the corresponding restriction fragment, (iii) the construction of the size-selected libraries from the fractionated genomic DNA, and (iv) the screening of the library to obtain an objective clone which is identified on the analytical genome scanning gel. A knowledge of the size distribution pattern of restriction fragments of the genomic DNA makes it possible to calculate the heterogeneity or complexity of the restriction fragment in each size-fraction. This manuscript first describes the distribution of the restriction fragments with respect to their length. Some examples of the practical application of this theory to genome scanning is then discussed using presumptive genome scanning gels. The way to calculate such DNA complexities in the prepared size-fractionated samples is also demonstrated. Such information should greatly facilitate the design of experimental strategies for the cloning of a certain size of genomic DNA after digestion with restriction enzyme(s) as is the case with genome scanning. PMID- 7774557 TI - Theoretical basis of one-dimensional genome scanning: a direct method to identify the site of a mutation. AB - Genome scanning is a technique designed to uncover a net genetic difference between otherwise identical DNA samples. As such, it can be used to directly identify the site of a gene mutation, facilitating the cloning of DNA fragments from that site. Unlike other conventional positional cloning methods, one dimensional genome scanning does not require prior knowledge of the location of the gene or mutation nor does it require closely linked markers. Rather, this method can directly identify the site of a net genomic change, such as a deletion or duplication caused by a mutation. Thus, the genome scanning method can be used in place of classic positional cloning strategies because prior positioning or mapping of the objective gene is unnecessary. By using this approach, we have identified and cloned a DNA fragment duplicated in the p(un) mutation of the mouse pink-eyed dilution locus (Brilliant et al., Science 1991, 252, 566-569). However, no other similar attempt using one-dimensional genome scanning has been reported so far, in spite of the simplicity of the procedure and its success in identifying and ultimately characterizing the pink-eyed dilution gene of the mouse. The lack of other reports of its success are perhaps not because of the practical difficulties of this method, but may be due to the false presumption that the probability for directly identifying the mutation site using genome scanning is extremely low. The theoretical probability was calculated and is presented here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774558 TI - Multilocus genomic mapping with intracisternal A-particle proviral oligonucleotide probes hybridized to mouse DNA in dried agarose gels. AB - Recently, oligonucleotide probes that detect intracisternal A-particle (IAP) gene subfamilies with a limited number of proviral copies have been shown to be useful multilocus markers. A procedure for hybridization of these probes has been developed and is described. In summary, the main features of the method are the following: (i) A pulse controller is used during agarose gel electrophoresis to improve resolution of restriction fragments in genomic DNA. (ii) Hybridization is performed in a dried gel. (iii) The hybridized gel is washed in tetramethylammonium chloride to eliminate differences in oligonucleotide composition on hybrid stability. Use of the procedure is demonstrated by genomic mapping of IAP loci in the AXB BXA recombinant inbred mouse strains, identification of hypomethylated loci in tumor cells, and detection of a transposed IAP provirus previously identified as the basis for a mutation at the agouti locus. PMID- 7774559 TI - An expanded system of restriction landmark genomic scanning (RLGS Ver. 1.8). AB - The restriction landmark genomic scanning (RLGS) method is a high-speed genome scanning system which is based on the concept that restriction enzyme sites can be used as landmarks throughout the genome. It employs direct end-labeling of the genomic DNA digested with a rare-cutting restriction enzyme, followed by high resolutional two-dimensional electrophoresis. Recently, this system was further developed to lower cost and to simplify the procedure. This paper reviews the RLGS principle and the breakthroughs enabling its further development. Also presented is the precise protocol of the newest version (RLGS Ver. 1.8) that offers cost effectiveness and an expanded production system. Finally, the advantages of this new RLGS method and prospects for its widespread application are discussed. PMID- 7774560 TI - A spot cloning method for restriction landmark genomic scanning. AB - We introduce two new methods for target cloning of DNA fragments corresponding to spots on the two-dimensional profile of restriction landmark genomic scanning (RLGS). One is a restriction trapper-based method and the other is a polymerase chain reaction (PCR) mediated method. Both are designed to select the target DNA fragments from a large amount of unlabeled background DNA fragments in the RLGS gel which produce background clones. The restriction trapper method is simple, with a cloning efficiency that is not biased by the length of the target DNA nor by its GC content. On the other hand, the PCR-mediated method is efficient for cloning DNA fragments from a small amount of starting materials. These methods provide us with powerful tools for isolating DNA clones identified by the RLGS system as interesting spots. This paper reports the precise protocols of these methods and discusses their application and usefulness. PMID- 7774561 TI - The use of restriction landmark genomic scanning to scan the mouse genome for endogenous loci with imprinted patterns of methylation. AB - Restriction landmark genomic scanning (RLGS) has been used to screen endogenous loci for imprinted patterns of methylation. The screening method is based upon the identification of genetic variation in RLGS profiles between different strains and determining whether specific variant landmarks are transmitted equally to the progeny of reciprocal F1 matings. The RLGS profiles of C57BL/6 (B6) and DBA/2 (D2) and their reciprocal hybrids were produced with two enzyme combinations that used NotI as the landmark enzyme and two combinations that used BssHII. An estimated 13% of the spots are either B5- or D2-specific in these tests, giving a total of nearly 1000 variant loci that were examined for imprinted methylation. Three candidate loci for imprinted regulation were identified in these analyses. We also used crosses of more genetically diverse parents to increase the number of variant loci screened. Interspecific crosses of B6 with the M. musculus strain PWK and intrasubspecific crosses between B6 and the M. molossinus strain MSM expanded the levels of variation between the parental strains in the cross to an estimated 31% and 26%, respectively. The RLGS patterns for one NotI combination and one BssHII profile were examined for each of these crosses, giving approximately 2000 additional loci that were screened for imprinted patterns of methylation. Eight loci with imprinted patterns of transmission were observed out of 3040 loci tested. The chromosomal locations for the three B6 and D2 specific loci, Irlgs 1-3, were identified using BXD recombinant inbred strain analysis. Irlgs 1 and 3 are B6- and D2-specific loci that had the same strain distribution pattern which mapped to the central region of chromosome 9.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774562 TI - Accessibility to tissue-specific genes from methylation profiles of mouse brain genomic DNA. AB - The DNA methylation status of a large number of genomic loci is visualized simultaneously and quantitatively as two-dimensional gel spots in the newly developed restriction landmark genomic scanning with a methylation-sensitive restriction enzyme (RLGS-M). Here, we demonstrate that RLGS-M using NorI as a methylation-sensitive enzyme could also scan gene loci of mammalian genomes, since almost all of the NotI loci corresponding to randomly chosen RLGS-M spots were located near or in transcriptional units (6 out of 7 NotI-linking clones) when mouse brain genomic DNA was used. This supports the previous prediction that most NotI sites are located in CpG islands (Lindsay and Bird, Nature 1987, 327, 336-338). Furthermore, beginning with RLGS-M spots we examined how to approach their corresponding RNA messages, whose expression may be associated with methylation. We compared RLGS-M patterns among various developmental stages of the mouse brain from embryonic day 9.5 to postnatal 8 weeks or among in vitro cell lines, and detected alterations of RLGS-M spots which were due to methylation of NotI sites. Two experiments using NotI-linking clones or polymerase chain reaction (PCR) were carried out to approach to their corresponding RNA messages. Consequently, we isolated two PCR-amplified clones (# 15 and # 91) which corresponded to methylatable loci and gave positive signals to mRNA from the adult brain. Furthermore, we identified two NotI-linking clones (C211 and C198) whose corresponding NotI loci localized near or at transcriptional units and were methylated in cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774564 TI - Genetic mapping of restriction landmark genomic scanning loci in the mouse. AB - Restriction landmark genomic scanning (RLGS) was originally proposed as a high speed method for surveying a large number of restriction landmarks in genomic DNA. The effort to apply this method to genetic analysis has been made, resulting in developing the new approach for the rapid construction of the genetic map of complex mammalian genomes (RLGS spot mapping). Especially, the use of NotI as the restriction landmark for genetic studies suggests that there is a high probability that a significant number of these RLGS loci will be associated with CpG islands of functional genes. Moreover, it is possible to use the RLGS spot mapping to analyze genetic map-poor species very rapidly for linkage of recessive mutations or segregating traits, because it does not rely upon cloned probes or sequences. In this paper, we summarize the progress that has been made in the practical application of the RLGS method to genetic analysis using congenic strains, recombinant inbred (RI) strains, and in interspecific backcrosses of mice. PMID- 7774563 TI - Demethylation of a repetitive DNA sequence in human cancers. AB - To detect DNA alterations in unknown regions in human cancers, we have performed restriction landmark genomic scanning (RLGS) analysis of DNA isolated from cancer and normal cells. One spot with a highly intensified signal was detected in DNA from all six malignant melanoma cell lines, two of five colon cancer cell lines and one of six pancreatic cancer cell lines analyzed. In DNA from normal cells, two placentas and seven cultured lymphocytes, the signal of this spot was not intense. The DNA fragment corresponding to the spot was cloned. By nucleotide sequence analysis, the DNA fragment was revealed to be a part of a repeating unit of a 13 kbp nucleotide sequence of which 200 copies were located in chromosome 8q21. Southern blotting analysis using the cloned fragment as a probe demonstrated that the intensified signal for the DNA fragment observed in cancer cells was due to demethylation in the recognition sequence of the NotI restriction enzyme. The results suggest that marked demethylation in the repeating units might be associated with the genesis or progression of some types of cancers. PMID- 7774565 TI - Quantitative and qualitative genetic variation in two-dimensional DNA gels of human lymphocytoid cell lines. AB - There is a continuing need for more efficient methods to examine human (and other) populations for altered germinal and somatic cell mutation rates. To this end, we have explored the potential usefulness of two-dimensional (2-D) electrophoresis of human DNA fragments obtained from restriction-enzyme-digested genomic DNA, using samples from father/mother/child trios. On a single 2-D DNA preparation, approximately 2000 DNA fragments varying in size from 1.0 to 5.0 kbp in the first dimension and 0.3 to 2.0 kbp in the second dimension are visualized. To enter into a genetic analysis of quantitative variation, these fragments must exhibit positional and quantitative stability. With respect to the latter, if spots that are the product of two homologous DNA fragments are to be distinguished with the requisite accuracy from spots that are the product of only one fragment, the coefficient of variation of spot intensity should be approximately < or = 0.12. At present, 482 of the spots in our preparations meet these standards. In an examination of preparations based on three Japanese mother/father/child trios, 43 of these 482 spots were found to exhibit variations that segregated within families according to Mendelian principles. Additionally, of the 2000 spots, 1114 (of which the aforementioned 482 are a subset) were deemed appropriate for the study of qualitative variation. A total of 142 variable spots were identified; the heterozygosity index for these DNA fragments was 4.4%. The genetic nature of the additional variants was again established by their segregation according to Mendelian principles. We have established the feasibility of cloning fragments from such gels and determining their nucleotide sequence. This technology should be highly efficient in monitoring for mutation resulting in loss/gain/rearrangement events in DNA fragments distributed throughout the genome. PMID- 7774566 TI - A single gel analysis of 575 dominant and codominant restriction landmark genomic scanning loci in mice interspecific backcross progeny. AB - We identified 575 new NotI landmarks of C57BL/6(B)- and M. spretus (S)-specific, dominant and codominant loci which were segregated in B x S interspecific backcrosses (BSS), using the restriction landmark genomic scanning (RLGS) spot mapping method. All of these loci were visualized on a single RLGS profile which was produced with NotI-PvuII-PstI. These landmarks include 250 newly identified S specific spots in addition to the previously reported 325 B-specific spots. The S specific spots were identified by reading full or half intensity, based on the property that the spot intensity of the autoradiographic signal reflected the copy number of an end-labeled restriction landmark. The cumulative map is 1341 cM and it is based upon 985 meiotic events in 72 backcross progeny. This map covers 90% of the total estimated length of the mouse genetic map. This map provides a good tool for the high-speed genome scanning assay in the mouse genome by a single RLGS gel analysis. PMID- 7774568 TI - High resolution microscopic mapping of DNA using multi-color fluorescent hybridization. AB - We describe a procedure for microscopically mapping the relative positions of DNA probes along extended strands of DNA. The procedure referred to as direct visual hybridization (DIRVISH) DNA mapping involves the simultaneous hybridization of multiple probes and the fluorescent colors, red green and blue to produce images that convey high-resolution mapping information. The images appear as long strings of fluorescent signals positioned as they are in the genome. A visual multi-color map is generated within 2 days. Cosmid probes span a distance of 10 microms or more and have been observed to contain patterns within the strings of signals. We have developed computer imaging programs to scan through the strings of signals and plot the intensities. Scans through multiple signal strings for one cosmid probe revealed consistent patterns. We have interpreted the patterns as the result of suppression of repetitive DNA sequence hybridization. These patterns may prove useful as fingerprints for regions of DNA. PMID- 7774567 TI - Application of fluorescence in situ hybridization in genome analysis of the mouse. AB - Fluorescence in situ hybridization (FISH) is an effective technique for localizing cloned DNA probes directly onto metaphase chromosomes. Human genome mapping using FISH has been significantly enhanced by the development of new techniques, especially high-resolution gene mapping with direct R-banding FISH and physical gene ordering with multi-color FISH. By contrast, FISH techniques have not been put to practical use for the analysis of the mouse genome compared with the human. We have developed and modified FISH techniques for use in mouse genome analysis. In this article we summarize and review our recent results with FISH analyses in the following studies: (i) high-resolution gene mapping with the direct R-banding FISH, (ii) analysis of chromosomal rearrangement with multi color FISH, (iii) establishment of centromere mapping with the major satellite DNA probe, (iv) analysis of chromatin structure in meiotic cells, and (v) application of FISH in cytogenetic studies of genetic variation in the mouse, showing that these applications of FISH are very useful for mouse genome analysis. PMID- 7774570 TI - Differential cloning using in-gel competitive reassociation. AB - We describe the principle and actual processes of a differential cloning procedure designed for cloning of anonymous restriction DNA fragments whose molecular sizes differ between two genomic DNA preparations from higher organisms as a result of DNA rearrangement, polymorphism, etc. The procedure, which was extensively modified from the original one and still employs in-gel competitive reassociation (IGCR) as the basic principle, aims for cloning of DNA fragments which exist in one copy or less per mammalian genome. The modified procedure consists of dissociation and reassociation of biotinylated restriction digests of target DNA fragments (from which clones are to be isolated) in the presence of a large excess of reference (competitor) DNA in gel after electrophoresis, which is followed by absorption of the target DNA fragments to streptavidin-coated tubes and solid-phase polymerase chain reaction. After repeating these steps we attained substantial enrichment of altered DNA fragments which were originally present in one copy or less per complex mammalian genome. PMID- 7774569 TI - Genomic mismatch scanning: current progress and potential applications. AB - Genomic mismatch scanning (GMS) is a new method of genetic mapping which attempts to purify and map the regions of identity between two complex genomes in a single test. Identical DNA fragments from two genomic sources are enriched in two steps: (i) after reannealing of the two genomes, heterohybrids are purified by using a combination of a restriction methylase and methylation-sensitive endonucleases, (ii) heterohybrids that contain mismatches are nicked in vitro by the E. coli MutHLS mismatch repair system and are eliminated subsequently from the pool, leaving only mismatch-free heterohybrids. The genomic origin of this selected pool of DNA fragments is then mapped in a single hybridization step onto metaphase chromosomes or ordered DNA arrays. The principal advantages of GMS are (i) it approaches the theoretical limit of mapping power and resolution offered by an arbitrarily dense set of completely informative polymorphic markers and (ii) it results in a great increase in the effective number of informative markers without a corresponding increase in the number of individual tests. Thus, it should provide an efficient method for affected-relative-pair linkage mapping and for linkage disequilibrium mapping. In addition, a variation of GMS may allow rapid genomic scanning for regions of homozygosity-by-descent or somatic loss-of heterozygosity. The feasibility of GMS has been validated in the 15 mb genome of Saccharomyces cerevisiae. This article discusses the principles of GMS, the application to more complex genomes, and the possible uses of GMS. PMID- 7774571 TI - Crystal structure of a theta-class glutathione transferase. AB - Glutathione S-transferases (GSTs) are a family of enzymes involved in the cellular detoxification of xenotoxins. Cytosolic GSTs have been grouped into four evolutionary classes for which there are representative crystal structures of three of them. Here we report the first crystal structure of a theta-class GST. So far, all available GST crystal structures suggest that a strictly conserved tyrosine near the N-terminus plays a critical role in the reaction mechanism and such a role has been convincingly demonstrated by site-directed mutagenesis. Surprisingly, the equivalent residue in the theta-class structure is not in the active site, but its role appears to have been replaced by either a nearby serine or by another tyrosine residue located in the C-terminal domain of the enzyme. PMID- 7774572 TI - Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells. AB - Bacterial invasion of human mucosal cells is considered to be a primary event in the pathogenesis of a gonococcal infection. Here we report that cell surface heparan sulfate proteoglycans may play a role in the establishment of an infection, by functioning as receptors for the invasion-promoting gonococcal opacity protein adhesin. Chemical modification and enzymatic removal of proteoglycan receptors from cultured epithelial cells abolished opacity protein associated gonococcal invasion, and mutant cell lines defective in proteoglycan synthesis were poor substrates for gonococcal attachment. The addition of purified receptor and receptor analogues totally blocked gonococcal entry into the cells. Heparin-affinity chromatography and receptor binding assays using recombinant bacteria producing defined opacity proteins and reconstituted receptor or purified receptor fragments as probes, identified one particular member of the opacity protein family (MS11-Opa30) as the primary ligand for this novel class of receptors for bacteria. Heparan sulfate proteoglycans with gonococcal binding activity were purified from various cell types derived from target tissues of gonococcal infection, including ME-180 endocervical cells and primary cultures of human corneal epithelium. The physico-chemical properties of the receptor indicate that it may belong to the syndecan proteoglycan family. PMID- 7774573 TI - Dominant mutants identify new roles for p34cdc2 in mitosis. AB - A large number of dominant mutants have been generated in the fission yeast cdc2 gene, causing lethality when expressed in wild-type cells. The mutants interfere with distinct aspects of p34cdc2 function, producing one of four different phenotypes: mitotic arrest, multiple rounds of S phase in the absence of mitosis, premature mitosis or G2 arrest. The mitotic mutants DL41, DL45 and DL50 are characterized in this paper. Over-expression of DL41 or DL45 causes mitotic arrest, specifically interfering with sister chromatid separation, without preventing spindle elongation. This suggests a role for p34cdc2 in triggering sister chromatid separation at anaphase. DL41 and DL45 also cause abnormal septum formation, suggesting that p34cdc2 may also be involved in regulating this process in fission yeast. These mitotic aspects of p34cdc2 function may involve interaction with p13suc1, since increased expression of suc1 partially suppresses DL41 and DL45. Over-expression of DL50 causes premature mitotic entry in cells that have not completed S phase, resulting in lethality. DL41, DL45 and DL50 correspond to mutation of p34cdc2 residues predicted to be on the surface of the protein, identifying potential sites of interaction with mitotic regulators of p3cdc2, and these residues are conserved amongst cdc2 proteins found in other eukaryotes. PMID- 7774574 TI - Cell cycle regulation of human WEE1. AB - WEE1 kinase negatively regulates entry into mitosis by catalyzing the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase. We report here an investigation of human WEE1. Endogenous WEE1 migrates as an approximately 94 kDa protein in SDS PAGE, substantially larger than the 49 kDa protein encoded by the original human WEE1 cDNA clone that was truncated at the 5'-end. Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates, hence it is likely to have an important role in the mitotic control of human cells. WEE1 activity was not found to be elevated in HeLa cells arrested in S phase, suggesting that unreplicated DNA does not delay M phase by hyperactivating WEE1. WEE1 activity is strongly suppressed during M phase, suggesting that negative regulation of WEE1 could be part of the mechanism by which activation of CDC2/cyclin B kinase is promoted during the G2/M transition. M phase WEE1 is re-activated in samples prepared in the absence of protein phosphatase inhibitors, demonstrating that WEE1 is inhibited by a mechanism that requires protein phosphorylation. PMID- 7774575 TI - Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. AB - Using a three-dimensional model of G protein-coupled receptors (GPCR), we have previously succeeded in docking the neurohypophysial hormone arginine-vasopressin (AVP) into the V1a receptor. According to this model, the hormone is completely embedded in the transmembrane part of the receptor. Only the side chain of the Arg residue at position 8 projects outside the transmembrane core of the receptor and possibly interacts with a Tyr residue located in the first extracellular loop at position 115. Residue 8 varies in the two natural neurohypophysial hormones, AVP and oxytocin (OT); similarly, different residues are present at position 115 in the different members of the AVP/OT receptor family. Here we show that Arg8 is crucial for high affinity binding of AVP to the rat V1a receptor. Moreover, when Tyr115 is replaced by an Asp and a Phe, the amino acids naturally occurring in the V2 and in the OT receptor subtypes, the agonist selectivity of the V1a receptor switches accordingly. Our results indicate that the interaction between peptide residue 8 and the receptor residue at position 115 is not only crucial for agonist high affinity binding but also for receptor selectivity. PMID- 7774576 TI - Heparin can activate a receptor tyrosine kinase. AB - Heparin, a densely sulfated glycosaminoglycan produced by mast cells, is best known for its inhibitory effects on the blood coagulation system. Heparin or heparan sulfate proteoglycans are also essential cofactors for the interaction of fibroblast growth factors (FGFs) with their receptor tyrosine kinases (FGFRs). Here we show that heparin is a growth factor-independent activating ligand for FGFR-4. Heparin stimulates FGFR-4 autophosphorylation on transfected myoblasts, fibroblasts and lymphoid cells, and is most potent on cells lacking surface heparan proteoglycan. Two functional analogs of heparin, fucoidan and dextran sulfate, are also activators of FGFR-4, while neither heparin nor its analogs can stimulate FGFR-1 in the absence of FGF. A mutation in the FGFR-4 ectodomain which impairs receptor activation by FGFs does not interfere with activation by heparin, demonstrating that receptor domains required for heparin or FGF activation are not identical. Heparin activation of FGFR-4 or of a chimeric receptor bearing FGFR-4 ectodomain and FGFR-1 cytodomain triggers downstream tyrosine phosphorylation of several signaling proteins, and induces proliferation of cells bearing the chimeric receptor. Consistent with these findings, a soluble FGFR-4 ectodomain has strong FGF-independent affinity for immobilized heparin resin, while soluble FGFR-1 requires FGF for stable heparin interaction. Heparin activation of FGFR-4 is the first example of a mammalian polysaccharide serving as a signaling ligand. PMID- 7774578 TI - GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex. AB - The TGF-beta type II receptor (T beta R-II) is a transmembrane serine/threonine kinase that, upon ligand binding, recruits and phosphorylates a second transmembrane kinase, T beta R-I, as a requirement for signal transduction. T beta R-I is phosphorylated by T beta R-II in the GS domain, a 30 amino acid region preceding the kinase domain and conserved in type I receptors for other TGF-beta-related factors. The functional role of seven serines and threonines in the T beta R-I GS domain was investigated by mutational analysis. Five of these residues are clustered (TTSGSGSG) in the middle of the GS domain. Mutation of two or more of these residues impairs phosphorylation and signaling activity. Two additional threonines are located near the canonical start of the kinase domain, and their individual mutation to valine strongly inhibits receptor phosphorylation and signaling activity. Replacement of one of these residues, Thr204, with aspartic acid yields a product that has elevated in vitro kinase activity and signals anti-proliferative and transcriptional responses in the absence of ligand and T beta R-II. The identification of constitutively active T beta R-I forms confirms the hypothesis that this kinase acts as a down-stream signaling component in the TGF-beta receptor complex, and its activation by T beta R-II or by mutation is necessary and sufficient for propagation of anti proliferative and transcriptional responses. PMID- 7774577 TI - Affinity and specificity requirements for the first Src homology 3 domain of the Crk proteins. AB - The specificity of SH3 domain complex formation plays an important role in determining signal transduction events. We have previously identified a highly specific interaction between the first CrkSH3 domain [CrkSH3(1)] and proline-rich sequences in the guanine nucleotide exchange factor C3G. A 10 amino acid peptide derived from the first proline-rich sequence (P3P4P5A6L7P8P9K10K11R12) bound with a Kd of 1.89 +/- 0.06 microM and fully retained the high affinity and unique selectivity for the CrkSH3(1) domain. Mutational analysis showed that P5, P8, L7 and K10 are critical for high affinity binding. A conservative mutation, K10R, significantly decreased the affinity for the CrkSH3(1) domain while increasing the affinity for Grb2. Comparative binding studies with the K10R and K10A mutant peptides to c-Crk and v-Crk further suggested that K10 binds via a charge dependent and a charge-independent interaction to the RT loop of the CrkSH3(1) domain. Besides determining important structural features necessary for high affinity and specificity binding to the CrkSH3(1) domain, our results also demonstrate that a conservative mutation in a single amino acid can significantly alter the specificity of an SH3 binding peptide. PMID- 7774579 TI - Energy-dependent chromatin accessibility and nucleosome mobility in a cell-free system. AB - Chromatin structure must be flexible to allow the binding of regulatory proteins and to accommodate different levels of gene activity. Chromatin assembled in a cell-free system derived from Drosophila embryos contains an activity that hydrolyses ATP to render entire nucleosome arrays mobile. Nucleosome movements, most likely their sliding, occurred even in the presence of the linker histone H1. The dynamic state of chromatin in the presence of the activity and ATP globally increased the accessibility of nucleosomal DNA to incoming proteins. This unprecedented demonstration of energy-dependent nucleosome mobility identifies a new principle which is likely to be fundamental to the mechanism of chromatin remodelling and the binding of regulatory proteins. PMID- 7774580 TI - A transition in transcriptional activation by the glucocorticoid and retinoic acid receptors at the tumor stage of dermal fibrosarcoma development. AB - In transgenic mice harboring the bovine papillomavirus genome, fibrosarcomas arise along an experimentally accessible pathway in which normal dermal fibroblasts progress through two pre-neoplastic stages, mild and aggressive fibromatosis, followed by a final transition to the tumor stage. We found that the glucocorticoid receptor (GR) displays only modest transcriptional regulatory activity in cells derived from the three non-tumor stages, whereas it is highly active in fibrosarcoma cells. Upon inoculation into mice, the aggressive fibromatosis cells progress to tumor cells that have high GR activity; thus, the increased transcriptional regulatory activity of GR correlates with the cellular transition to the tumor stage. The intracellular levels of GR, as well as its hormone-dependent nuclear translocation and specific DNA binding activities, are unaltered throughout the progression. Strikingly, the low GR activity observed in the pre-neoplastic stages cannot be overcome by exogenous GR introduced by co transfection. Moreover, comparisons of primary embryo fibroblasts and their transformed derivatives revealed a similar pattern--modest GR activity, unresponsive to overexpressed GR protein, in the normal cells was strongly increased in the transformed cells. Likewise, the retinoic acid receptor (RAR) displayed similar differential activity in the fibrosarcoma pathway. Thus, the oncogenic transformation of fibroblasts, and likely other cell types, is accompanied by a striking increase in the activities of transcriptional regulators such as GR and RAR. We suggest that normal primary cells have a heretofore unrecognized capability to limit the magnitude of induction of gene expression. PMID- 7774581 TI - Multiple modes of dorsal-bHLH transcriptional synergy in the Drosophila embryo. AB - Synergistic interactions between the maternal regulatory factor dorsal (dl) and basic helix-loop-helix (bHLH) activators are essential for initiating differentiation of the mesoderm and neuroectoderm in the early Drosophila embryo. Here we present evidence that dl-bHLH interactions mediating gene expression in the neuroectoderm and mesoderm are fundamentally distinct. Close proximity of dl and bHLH binding sites is essential for the synergistic activation of gene expression in the lateral neuroectoderm, where there are diminishing levels of the dl regulatory gradient. In contrast, sharp on/off patterns of gene expression in the presumptive mesoderm do not require linkage of these sites. Analysis of minimal and synthetic promoter elements suggests that dl and bHLH activators, such as twist, might interact with different rate-limiting components of the transcription complex. These results are consistent with two distinct modes of dl bHLH synergy: cooperative binding to DNA (requiring linkage of sites) and synergistic contact of basal transcription factors (not requiring linkage). Finally, the characterization of a 57 bp synthetic minimal stripe unit (MSU) provides evidence for a third tier of dl-bHLH synergy. Tandem copies of the MSU function as a bona fide enhancer and can mediate neuroectoderm expression in transgenic embryos even when placed 4.5 kb downstream of a test promoter. Multiple copies of the MSU function synergistically only when linked, but not when separated. We propose that this linkage requirement provides the basis for the evolution of modular promoters composed of discrete, non-overlapping enhancers. PMID- 7774582 TI - Mutations in GCD11, the structural gene for eIF-2 gamma in yeast, alter translational regulation of GCN4 and the selection of the start site for protein synthesis. AB - Translation initiation factor 2 (eIF-2) in eukaryotic organisms is composed of three non-identical subunits, alpha, beta and gamma. In a previous report, we identified GCD11 as an essential gene encoding the gamma subunit of eIF-2 in the yeast Saccharomyces cerevisiae. The predicted amino acid sequence of yeast eIF-2 gamma displays remarkable similarity to bacterial elongation factor Tu, including the presence of sequence elements conserved in all known guanine nucleotide binding proteins. We have identified the molecular defects present in seven unique alleles of GCD11 characterized by a partial loss of function. Three of these mutations result in amino acid substitutions within the putative GTP binding domain of eIF-2 gamma. We show that the gcd11 mutations specifically alter regulation of GCN4 expression at the translational level, without altering the scanning mechanism for protein synthesis initiation. Six of the mutant alleles presumably alter the function of eIF-2 gamma, rather than its abundance. A single allele, gcd11-R510H, suppresses a mutant his4 allele that lacks a functional AUG start codon. The latter result indicates that the gamma subunit of eIF-2 participates in recognition of the start site for protein synthesis, a role previously demonstrated in yeast for eIF-2 alpha and eIF-2 beta. PMID- 7774583 TI - A novel endocytosis signal related to the KKXX ER-retrieval signal. AB - Membrane proteins often contain a sorting signal in their cytoplasmic tail that promotes their clustering into coated vesicles at a specific cellular site. ERGIC 53 contains a cytoplasmic ER-retrieval signal, KKFF. However, overexpressed ERGIC 53 is transported to the cell surface and rapidly endocytosed. Here we report that ERGIC-53 carries a previously undescribed endocytosis signal. Surprisingly, the signal was KKFF and like the ER-retrieval signal required a C-terminal position. In fact, the minimal consensus sequence determined by substitutional mutagenesis (K-K/R-F/Y-F/Y) was related to the ER-retrieval consensus (K-K-X-X). Furthermore, we provide evidence that internalization of VIP36, a protein that cycles between plasma membrane and Golgi, is mediated by a signal at its C terminus that matches the internalization consensus sequence. The relatedness of the two signals suggests that coatomer-mediated retrieval of proteins may be mechanistically more related to clathrin-dependent sorting than previously anticipated. PMID- 7774584 TI - A tyrosine-containing motif mediates ER retention of CD3-epsilon and adopts a helix-turn structure. AB - The CD3-epsilon endoplasmic reticulum (ER) retention motif has been characterized by mutagenesis and NMR spectroscopy. Tyr177, Leu180 and Arg183 are involved in ER retention. The motif forms an elongated alpha-helix in which the tyrosine and leucine residues are closely apposed, followed by a beta I' turn that places Arg183 in the vicinity of Leu180. The structure formed by Tyr177 and the leucine in position +3 is reminiscent of the beta-turn structure adopted by tyrosine containing endocytosis signals. Moreover, substitution of the transferrin receptor (TfR) internalization sequence by the CD3-epsilon motif still allowed the rapid internalization of the TfR and, conversely, the chimeric protein resulting from the substitution of the CD3-epsilon motif by the endocytosis signal of the low density lipoprotein receptor was ER located. These data support the idea of a functional homology between the two types of signal. PMID- 7774585 TI - 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein. AB - The low density lipoprotein receptor-related protein (LRP) is a multifunctional endocytic receptor with the ability to bind and endocytose several structurally and functionally distinct ligands. A 39 kDa receptor-associated protein (RAP) inhibits all ligand interactions with LRP in vitro. In the present study, we demonstrate that RAP is an endoplasmic reticulum (ER) resident protein. The tetrapepetide sequence HNEL at the C-terminus of RAP is both necessary and sufficient for RAP retention within the ER. Metabolic labeling combined with cross-linking studies show that RAP interacts with LRP in vivo. Pulse-chase analysis reveals that this association is transient early in the secretory pathway and coincides with LRP aggregation and reduced ligand binding activity. Both internal triplicated LRP binding domains on RAP and multiple RAP binding domains on LRP appear to contribute to the aggregation of LRP and RAP. Dissociation of RAP from LRP results from the lower pH encountered later in the secretory pathway and correlates with an increase in LRP ligand binding activity. Taken together, our results thus suggest that RAP functions intracellularly as a molecular chaperone for LRP and regulates its ligand binding activity along the secretory pathway. PMID- 7774586 TI - Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. AB - The Hsp70 family of molecular chaperones has an essential role in the synthesis, folding and translocation of the nascent peptide chain. While the general features of these activities are well documented, less is understood about the regulation of these activities. The ATPase rate is stimulated by non-native proteins, furthermore, interaction with ATP leads to the release of protein substrate concurrent with a conformational change in Hsp70. One interpretation of these data is that the two domains of Hsp70 interact. In the process of mapping the carboxyl-terminal boundary of the substrate binding domain for human Hsp70, we identified a regulatory motif, EEVD, which is conserved at the extreme carboxyl terminus among nearly all cloned cytosolic eukaryotic Hsp70s. Deletion or mutation of EEVD affects the ATPase activity, the ability to interact with substrates, and interferes with the ability of the mutant Hsp70 to interact with HDJ-1 in the refolding of denatured firefly luciferase. Examination of the biophysical properties of the mutant Hsp70s reveals a change in the overall shape and conformation of the protein consistent with reduced interactions between the two domains. These data suggest that the EEVD motif is involved in the intramolecular regulation of Hsp70 function and intermolecular interactions with HDJ-1. PMID- 7774587 TI - Dynamic interaction of the protein translocation systems in the inner and outer membranes of yeast mitochondria. AB - Mitochondria contain two distinct protein import systems, one in the outer and the other in the inner membrane. These systems can act independently of one another in submitochondrial fractions of if a protein is transported to the outer membrane or to the intermembrane space. It has been proposed that the two systems associate reversibly when a protein is transported across both membranes, but this hypothesis has remained unproven. In order to address this question, we have checked whether antibodies against a subunit of one system can co immunoprecipitate subunits of the other system. We find that the two systems associate stably if a matrix-targeted precursor is arrested during import; no association is seen in the absence of a stuck precursor. These experiments provide direct evidence that protein import into the mitochondrial matrix is mediated by the reversible interaction of the two translocation systems. PMID- 7774588 TI - Protein secretion by hybrid bacterial ABC-transporters: specific functions of the membrane ATPase and the membrane fusion protein. AB - The Erwinia chrysanthemi metalloprotease C and the Serratia marcescens haem acquisition protein HasA are both secreted from Gram-negative bacteria by a signal peptide-independent pathway which requires a C-terminal secretion signal and a specific ABC-transporter made up of three proteins: a membrane ATPase (the ABC-protein), a second inner membrane component belonging to the membrane fusion protein family and an outer membrane polypeptide. HasA and protease C transporters are homologous although the secreted polypeptides share no sequence homology. Whereas protease C can use both translocators, HasA is secreted only by its specific transporter. Functional analysis of protease C and HasA secretion through hybrid transporters obtained by combining components from each system demonstrates that the ABC-protein is responsible for the substrate specificity and that inhibition of protease C secretion in the presence of HasA results from a defective interaction between HasA and the ABC-protein. We also show that the outer membrane protein, TolC, can combine with the membrane fusion protein HasE in the presence of either ABC-protein to form a functional transporter but not with the membrane fusion protein, PrtE. This indicates a specific interaction between the outer membrane component and the membrane fusion protein. PMID- 7774590 TI - Disassembly of the reconstituted synaptic vesicle membrane fusion complex in vitro. AB - The interaction of the presynaptic membrane proteins SNAP-25 and syntaxin with the synaptic vesicle protein synaptobrevin (VAMP) plays a key role in the regulated exocytosis of neurotransmitters. Clostridial neurotoxins, which proteolyze these polypeptides, are potent inhibitors of neurotransmission. The cytoplasmic domains of the three membrane proteins join into a tight SDS resistant complex (Hayashi et al., 1994). Here, we show that this reconstituted complex, as well as heterodimers composed of syntaxin and SNAP-25, can be disassembled by the concerted action of the N-ethylmaleimide-sensitive factor, NSF, and the soluble NSF attachment protein, alpha-SNAP. alpha-SNAP binds to predicted alpha-helical coiled-coil regions of syntaxin and SNAP-25, shown previously to be engaged in their direct interaction. Synaptobrevin, although incapable of binding alpha-SNAP individually, induced a third alpha-SNAP binding site when associated with syntaxin and SNAP-25 into heterotrimers. NSF released prebound alpha-SNAP from full-length syntaxin but not from a syntaxin derivative truncated at the N-terminus. Disassembly of complexes containing this syntaxin mutant was impaired, indicating a critical role for the N-terminal domain in the alpha-SNAP/NSF-mediated dissociation process. Complexes containing C-terminally deleted SNAP-25 derivatives, as generated by botulinal toxins type A and E, were dissociated more efficiently. In contrast, the N-terminal fragment generated from synaptobrevin by botulinal toxin type F produced an SDS-sensitive complex that was poorly dissociated. PMID- 7774589 TI - Embryonic tissue differentiation in Caenorhabditis elegans requires dif-1, a gene homologous to mitochondrial solute carriers. AB - The dif-1 gene was identified in a general screen for maternal-effect embryonic lethal (Mel) mutants. dif-1 mutant embryos complete gastrulation and embryonic cell division normally, but then arrest development with only a small amount of tissue differentiation. Either maternal or zygotic dif-1 activity is sufficient for wild-type development. The temperature-sensitive period of a cold-sensitive dif-1 mutant shows that dif-1 activity is essential only for 3 h, corresponding to the major period of embryonic tissue differentiation, and is not required post embryonically. The results point to a role for dif-1 in the maintenance of tissue differentiation in the developing embryo, but not for its initiation. Cloning and sequencing of the dif-1 gene revealed that its product is homologous to proteins in the mitochondrial carrier family. Although dif-1 activity is required only during embryogenesis, dif-1 RNA is expressed at all stages of development. In situ hybridization to embryos showed that dif-1 RNA is initially present in all cells of the embryo; this most likely corresponds to maternal dif-1 RNA. Later, the presumable zygotic dif-1 RNA is found only in the gut and hypodermis of the embryo. This tissue-specific expression raises the possibility that the dif-1 protein acts non-cell autonomously and that some communication or molecular transport dependent on DIF-1 takes place during embryonic tissue differentiation. dif-1 is the first mitochondrial carrier homologue known to be needed specifically for a developmental process. PMID- 7774591 TI - Retroviral sequences located within an intron of the dilute gene alter dilute expression in a tissue-specific manner. AB - The murine dilute coat color locus encodes an unconventional myosin heavy chain that is thought to be required for the elaboration or maintenance of dendrites or organelle transport in melanocytes and neurons. In previous studies we showed that the d mutation carried by many inbred strains of mice (now referred to as dilute viral, dv), is caused by the integration of an ecotropic murine leukemia virus (Emv-3) into the dilute gene and that phenotypic revertants of dv (termed d+) result from viral excision; a solo viral long terminal repeat (LTR) is all that remains in revertant DNA. In the studies described here we show that Emv-3 sequences are located within an intron of the dilute gene in a region of the C terminal tail that is differentially spliced. We also show that these Emv-3 sequences result in the production of shortened and abnormally spliced dilute transcripts and that the level of this effect varies among tissues. This tissue specific effect on dilute expression likely accounts for the absence of neurological abnormalities observed in dv mice. Surprisingly, we also found that the solo viral LTR present in revertant d+ DNA produces a tissue-specific effect on dilute expression, although this effect is less dramatic than with the full length provirus and produces no obvious mutant phenotype. These findings have important implications for understanding the effects of viral sequences on mammalian gene expression. PMID- 7774593 TI - Transposon-mediated chromosomal rearrangements and gene duplications in the formation of the maize R-r complex. AB - R-r controls the production of anthocyanin pigment in plant parts and the aleurone layer of seeds through the production of a family of related transcriptional activating proteins of the helix-loop-helix type. The R-r complex comprises a series of repeated, homologous components arranged in both direct and inverted orientations. These include the P component, a simple R gene that confers pigmentation of plant parts, and the S subcomplex that consists of a truncated inactive R gene called q, and two functional R genes, S1 and S2, that pigment the aleurone. The S genes are arranged in an unusual inverted head-to head orientation. The identity of each functional component was confirmed by microprojectile bombardment of intact maize tissues with cloned genomic DNA and by analysis of in vivo mRNA populations. Sequence analysis suggests that the S subcomplex was derived through the rearrangement of a simple P-like progenitor element. At the rearrangement breakpoints, features typical of the CACTA family of transposable elements were found. The location and arrangement of these CACTA element sequences implies that this element may have mediated the chromosomal rearrangements that led to the formation of the R-r complex. The unusual structure of R-r explains much of the meiotic instability of the complex. PMID- 7774592 TI - Loss of TAL-1 protein activity induces premature apoptosis of Jurkat leukemic T cells upon medium depletion. AB - Transcriptional activation of the tal-1 gene occurs in -30% of patients with T cell Acute Lymphoblastic Leukemia and is therefore likely to be involved in human T cell leukemogenesis. However, the TAL-1 protein functional properties involved in this process have not been assessed so far. We have derived a clonal subline of the Jurkat T cell line which produced solely a mutant truncated form of TAL-1 protein. Sequencing of genomic DNA and cDNAs showed that the only transcribed tal 1 allele of this mutant subline harbored a G nucleotide insertion at codon 270. The resulting frameshift modifies TAL-1 residues 272-278 and creates a stop at codon 279. Although the deletion of the 53 carboxy-terminal residues of the TAL-1 protein did not directly affect the TAL-1 basic helix-loop-helix domain (residues 185-243), it had drastic effects on TAL-1 functional properties, since the mutant subline exhibited a dramatic decrease of protein binding activity to the TAL-1 DNA consensus sequence. Growth curves indicated that the mutant subline exhibited premature apoptosis upon medium depletion or serum reduction when compared with the parental cells. However, no difference between Jurkat and the mutant subline was observed in etoposide- or Fas/APO-1-triggered apoptosis. Stable expression of the mutant TAL-1 protein in Jurkat cells resulted in a phenotype that was similar to that of the mutant Jurkat subline, indicating that the TAL-1 mutant protein behaved like a dominant negative mutant and that the premature apoptosis of the mutant subline upon medium depletion was the consequence of the loss of TAL-1 protein activity. PMID- 7774594 TI - RNA-mediated transposition of the tobacco retrotransposon Tnt1 in Arabidopsis thaliana. AB - The tobacco (Nicotiana tabacum) retrotransposon Tnt1 was introduced into Arabidopsis thaliana. In this heterologous host plant species, Tnt1 undergoes an RNA-mediated transposition and creates a 5 bp duplication at the insertion sites. This is the first report of transposition of a retrotransposon after introduction into a heterologous host species. Tnt1 transposed during in vitro regeneration of transformed A.thaliana, but no transposition event was detected as happening in T2 and T3 generation plants. Newly synthesized copies of Tnt1 can integrate into coding regions of the host DNA. Our results open up the possibility of using Tnt1 as a new tool for insertional mutagenesis and functional analysis of plant genomes, in addition to the strategies of T-DNA and transposon tagging. PMID- 7774595 TI - A domain sharing model for active site assembly within the Mu A tetramer during transposition: the enhancer may specify domain contributions. AB - The functional configuration of Mu transposase (A protein) is its tetrameric form. We present here a model for the organization of a functional Mu A tetramer. Within the tetramer, assembly of each of the two active sites for Mu end cleavage requires amino acid contributions from the central and C-terminal domains (domains II and III respectively) of at least two Mu A monomers in a trans configuration. The Mu enhancer is likely to function in this assembly process by specifying the two monomers that provide their C-terminal domains for strand cleavage. The Mu B protein is not required in this step. Each of the two active sites for the strand transfer reaction is also organized by domain sharing (but in the reverse mode) between Mu A monomers; i.e. a donor of domain II (also the recipient of domain III) during cleavage is a recipient of domain II (and the donor of domain III) during strand transfer. The function of the Mu B protein (which is required at the strand transfer step) and that of the enhancer element may be analogous in that their interactions with Mu A (domain III and domain I alpha respectively) promote conformations of Mu A conducive to strand cleavage or strand transfer. PMID- 7774597 TI - A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. AB - Many eukaryotic organisms, including humans, remove ultraviolet (UV) damage from their genomes by the nucleotide excision repair pathway, which requires more than 10 separate protein factors. However, no nucleotide excision repair pathway has been found in the filamentous fungus Neurospora crassa. We have isolated a new eukaryotic DNA repair gene from N.crassa by its ability to complement UV sensitive Escherichia coli cells. The gene is altered in a N.crassa mus-18 mutant and responsible for the exclusive sensitivity to UV of the mutant. Introduction of the wild-type mus-18 gene complements not only the mus-18 DNA repair defect of N.crassa, but also confers UV-resistance on various DNA repair-deficient mutants of Saccharomyces cerevisiae and a human xeroderma pigmentosum cell line. The cDNA encodes a protein of 74 kDa with no sequence similarity to other known repair enzymes. Recombinant mus-18 protein was purified from E.coli and found to be an endonuclease for UV-irradiated DNA. Both cyclobutane pyrimidine dimers and (6 4)photoproducts are cleaved at the sites immediately 5' to the damaged dipyrimidines in a magnesium-dependent, ATP-independent reaction. This mechanism, requiring a single polypeptide designated UV-induced dimer endonuclease for incision, is a substitute for the role of nucleotide excision repair of UV damage in N.crassa. PMID- 7774598 TI - Chimeric proteins containing the cytoplasmic domains of the mannose 6-phosphate receptors codistribute with the endogenous receptors. AB - We have constructed and transiently expressed in HeLa cells a series of hybrid proteins in which the cytoplasmic domain or both the transmembrane and the cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor were fused to the ectodomain of the hemagglutinin of the influenza virus (HA), a typical plasma membrane protein. In addition, we have expressed a hybrid protein containing the luminal domain of HA fused to the transmembrane and cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor. These hybrids were transported through and sorted from the secretory pathway as shown by acquisition of endo-H resistant oligosaccharides and their ability to recruit the Golgi assembly proteins AP-1 on the Golgi membrane. Like the mannose 6 phosphate receptors (MPRs), these hybrid proteins are also present in small amounts at the cell surface where they are likely to undergo endocytosis as disruption of the endocytosis signals contained in the MPR cytoplasmic domains induces their accumulation at the cell surface. Double immunofluorescence studies indicate that these chimeras codistribute with the endogenous MPRs at steady state. The results suggest that the cytoplasmic domains of the MPRs are sufficient to determine the steady-state distribution of the full-length proteins. PMID- 7774596 TI - Escherichia coli RecG and RecA proteins in R-loop formation. AB - Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. We found that a combination of an rnhA and a recG mutation is lethal to the cell. recG mutations that inactivate the helicase activity of RecG protein and inhibit reverse branch migration of Holliday junctions impart phenotypes resembling those of rnhA mutants. Thus, recG mutants display cSDR activity, and recG polA double mutants are inviable as are rnhA polA double mutants. These results suggest that the RecG helicase has a role in preventing R-loop formation. A model that R-loops are formed by assimilation of RNA transcripts into the duplex DNA is discussed. The model further postulates that RecA protein catalyzes this assimilation reaction and that RecG protein counteracts RecA in this reaction, resolves R-loops by its helicase activity, or does both. PMID- 7774599 TI - Role of free p70 (Ku) subunit in posttranslational stabilization of newly synthesized p80 during DNA-dependent protein kinase assembly. AB - The Ku antigen (p70/p80 heterodimer) is the DNA binding component of a DNA dependent serine/threonine kinase (DNA-PK), the catalytic activity of which is carried by a 350 kDa polypeptide (p350). In the present studies, the assembly of p70, p80, and p350 was investigated in human K562 (erythroleukemia) cells, and rabbit (RK13) or murine (L-929) cells infected with recombinant vaccinia viruses directing the synthesis of human p70 and p80. Pulse-chase analysis and density gradient centrifugation revealed a pool of free p70 subunits in K562 cells that dimerized within minutes with newly synthesized p80, whereas Ku became associated with newly synthesized p350 1 to 4 h after the onset of p70/p80 heterodimer assembly. A stable pool of free p80 subunits was not detected, and newly synthesized p80 was degraded rapidly (t1/2 < 1.5 h) unless it became incorporated into a p70/p80 dimer. The explanation for the absence of unassembled p80 subunits in K562 cells was investigated further by expressing human p70 and p80 individually or together in Ku-deficient RK13 or L-929 cells infected with recombinant vaccinia viruses p70-vacc and/or p80-vacc. As in uninfected K562 cells, the t1/2 of the free recombinant human p80 subunit expressed in RK13 cells was < 1.5 h unless it was "rescued" by dimerization with p70. The t1/2 of human p70 as well as p70/p80 heterodimers was > 16 h in RK13 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774600 TI - Truncation mutagenesis of the non-alpha-helical carboxyterminal tail domain of vimentin reveals contributions to cellular localization but not to filament assembly. AB - We have investigated the effect of stepwise truncating the carboxyterminal domain ("tail") of the intermediate filament (IF) protein vimentin of the clawed toad, Xenopus laevis, on filament assembly in vitro and, using cell transfection, in vivo and also on the cellular topology of the structures formed. All truncations examined, except the minimal one missing the last 11 amino acids which made the protein more sensitive to changes of ionic strength, did not significantly alter IF assembly in vitro, as judged by electron microscopy, viscometry and determination of viscoelastic properties with a laser-operated torsion pendulum. Stable transfections of vimentin-free mammalian cells with cDNAs encoding these mutations resulted at 28 degrees C, i.e. the permissive temperature for assembly of Xenopus vimentin, in the formation of extended IF bundle arrays. At 37 degrees C, however, the mutants lacking more than the last 35 amino acids could leave the cytoplasm and accumulated in the nucleus, indicating a certain topogenic element is located in the tail and directs cytoplasmic restriction in the wild-type protein although this does not form IFs under these conditions. Transfer to the nucleus is, however, abolished if the IF-consensus motif at the end of the rod domain is removed, suggesting that this part of the molecule also contributes to nuclear location. Similar results were obtained with human vimentin: While the rod entered the nucleus, headless vimentin, unable to form IFs, remained restricted to the cytoplasm owing to its tail domain. In contrast, tailless human vimentin and tailless mouse desmin, which are fully assembly-competent in vitro, both formed extensive IF arrays in the cytoplasm but did not accumulate in the nucleus. We conclude that in class III IF proteins stepwise deletions in the tail, while not considerably altering IF assembly in vitro, can change the topogenesis of IF proteins and structures in the living cell. PMID- 7774601 TI - Actin filaments are involved in cellular graviperception of the basidiomycete Flammulina velutipes. AB - Inhibitor studies demonstrate a major role of the actin cytoskeleton in cellular graviperception of the basidiomycete Flammulina velutipes. Treatment of explanted fruiting body stipes with 10(-4) M of the actin filament-disrupting agent cytochalasin D causes specific suppression of gravitropic curvature to 21% of the control value. Elongation growth is depressed to 48%. In contrast, curvature and elongation remain almost unaffected by 10(-4) M of the microtubule inhibitor oryzalin. Immunohistochemical labeling of actin filaments in stipe hyphae of Flammulina reveals a close colocalization with the nuclei. The label pattern is destroyed upon 10(-4) M cytochalasin treatment. The role of the actin cytoskeleton in graviperception in Flammulina parallels aspects of gravisensing in Chara rhizoids and thus points at basic similarities between fungal and plant mechanisms of cellular gravity perception. PMID- 7774602 TI - Effects of cytochalasin D on shape and fluid pinocytosis in human neutrophils as related to cytoskeletal changes (actin, alpha-actinin and microtubules). AB - We report that cytochalasin D (CD) is not a reliable tool to inhibit all forms of cell motility and actin polymerization in neutrophil granulocytes. In addition to the well-established effects of CD such as altered localization of F-actin, inhibition of surface ruffling, fluid pinocytosis and actin polymerization in agonist-stimulated cells, we find that in human neutrophils CD can 1) induce another type of continuous shape changes (10(-6) M and 10(-5) M CD), 2) stimulate fluid pinocytosis (10(-5) M CD), 3) increase actin polymerization (10(-5) to 10( 4) M CD) and alter the localization of F-actin and alpha-actinin (10(-6) to 10( 4) M CD). At 10(-5) M CD F-actin and alpha-actinin are preferentially located in different areas of the cell. At 10(-4) M CD actin and alpha-actinin may colocalize at the membrane but not in cytoplasmic foci. Thus, stimulation of shape changes, pinocytosis, actin polymerization and differential reorganization of the cytoskeleton occur at CD concentrations which are widely used to inhibit cell motility. The results show that CD is not a reliable tool to inhibit all movements of cells and actin polymerization in general. Shape changes, but not fluid pinocytosis and the relative redistribution of F-actin and alpha-actinin induced by 10(-5) M cytochalasin D are suppressed by 10(-5) colchicine. This indicates that also microtubules can play a role in determining neutrophil shape and movements. PMID- 7774603 TI - The perinuclear centriole-containing centrosome is not the major microtubule organizing center in Sertoli cells. AB - Microtubules are abundant in Sertoli cells and are predominantly arranged parallel to the long axis of the cell. In addition, the centrioles occur in a perinuclear position in the basal one third of the cell. In this study we investigate the importance of the perinuclear centriole-containing centrosome as a microtubule organizing center (MTOC) in Sertoli cells. In all experiments, rat testes were perfusion fixed and then processed for electron and/or fluorescence microscopy. For fluorescence microscopy, fragments or dissected pieces of seminiferous epithelium were labeled for tubulin and actin. The three-dimensional pattern of microtubules in Sertoli cells was determined using data collected with a confocal microscope and analyzed using the NIH-Image program (written by Wayne Rasband at the NIH). The detailed arrangement of microtubules around, and the number of microtubule ends associated with, the centrosome were determined from composite projections constructed from serial thin sections. The nucleating potential of the perinuclear centrosome was determined by perfusing testes for 6 h with 10 micrograms/ml nocodazole and then for up to 3 h with control buffer prior to fixation and analysis with confocal and standard fluorescence microscopy. Microtubules are not organized around a focal perinuclear site and few microtubule ends are associated with the centrosome. Moreover, in cells recovering from nocodazole treatment, microtubules first appear in apical (peripheral) processes. Our data indicate that the centriole-containing perinuclear centrosome is not a significant MTOC in Sertoli cells. Rather, microtubules are nucleated in peripheral regions and project basally. Based on the observations that microtubules appear to "cuff" the nucleus, intermediate filaments are concentrated around the nucleus, microtubules project into the perinuclear intermediate filament network, and microtubules and intermediate filaments are often coaligned, we suggest that microtubules are anchored into position at the base of the cell via linkages with the intermediate filament network. Our nucleation-anchorage model of microtubule organization in Sertoli cells may be applicable to other epithelial systems. PMID- 7774605 TI - Characterization of the binding of calmodulin to non-erythroid spectrin. AB - Both brain and erythrocyte spectrin bound calmodulin in a calcium-dependent manner when immobilized on a polyvinylidene difluoride (PVDF) membrane, though the affinity of the non-erythroid spectrin was much greater than that of the erythroid isoform. The interaction was characterized further using equilibrium partition. In the presence of calcium, the partition behavior of calmodulin was affected by both spectrins, though brain spectrin caused a much larger change in partition. However, in both cases it was evident that the observed partition behavior of calmodulin was due to complex formation with spectrin. Analysis of the equilibrium partition data indicated the presence of a high-affinity site characterized by a dissociation constant of about 0.3 microM and probably one or more much weaker sites (> 0.3 mM). The presence of at least two distinct binding sites was substantiated by the observation that truncated recombinant spectrin fusion proteins comprising either the middle part or the C-terminal of non erythroid alpha-spectrin bound calmodulin. PMID- 7774604 TI - Cell adhesion to the apical pole of epithelium: a function of cell polarity. AB - Human uterine epithelium displays a distinct polarized organization with apical, lateral, and basal plasma membrane domains. Although non-adhesive throughout most of the menstrual cycle, epithelial cells allow attachment of trophoblast cells to their apical pole during embryo implantation. A recent hypothesis postulates that epithelial cells turn off genes for apical-basal polarity and turn on genes for a more mesenchyme-like phenotype allowing cell-cell interaction with trophoblast. Using an in vitro assay human uterine cell lines (RL95-2, HEC-1-A, AN3-CA) were selected on the basis of adhesiveness for trophoblast-type cells (JAR). Subsequently, uterine cells were examined for epithelium-specific ultrastructure using transmission electron microscopy, and for the expression of E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits and cytokeratin using immunocytochemistry, confocal laser scanning microscopy, and surface replication technique. HEC-1-A monolayers are non-adhesive for JAR cells and appear highly polarized expressing E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits, and cytokeratin. Both, integrins and E-cadherin, are present at the lateral membrane. RL95-2 monolayers which are adhesive for JAR cells appear non-polarized. Like HEC 1-A cells, RL95-2 cells express E-cadherin, alpha 6-, beta 1-, and beta 4 integrin subunits, and cytokeratin. In contrast to HEC-1-A cells, integrins and E cadherin are distributed at the entire cell surface. AN3-CA monolayers are non adhesive for JAR cells and appear non-polarized. Cells lack epithelial-specific markers such as keratin and E-cadherin. They show only low expression of alpha 6 , beta 1-integrin subunits and lack beta 4-integrin subunit. Conversely, they express vimentin. Thus, modulation of the epithelial phenotype of uterine cells, i.e. loss of apical-basal polarity, might prepare the apical cell pole for cell cell interaction with trophoblast. However, loss of cell polarity would not lead to enhancement of adhesiveness for trophoblast if accompanied by a loss of epithelium-specific adhesion molecules. PMID- 7774606 TI - Purification, partial characterization and immunolocalization of a proteophosphoglycan secreted by Leishmania mexicana amastigotes. AB - The intracellular amastigote form of the parasitic protozoon Leishmania mexicana expresses a high-molecular weight phosphoglycan, which is antigenically related to the surface glycolipid lipophosphoglycan and the secreted enzyme acid phosphatase of Leishmania promastigotes. This antigen was purified from a cell free homogenate of infected mouse tissue and from amastigotes. Compositional and immunological analysis of the purified components indicate a proteophosphoglycan structure consisting of serine-rich polypeptide chains and mild acid-labile phosphooligosaccharides capped by mannooligosaccharides. Immunofluorescence and immunoelectron microscopy of parasitized mouse peritoneal macrophages and infected mouse tissue suggest that the proteophosphoglycan is secreted in large amounts by amastigotes via their flagellar pockets into the parasitophorous vacuoles of host cells. In some infected macrophages proteophosphoglycan is also located in vesicles apparently originating from the parasitophorous vacuole, which demonstrates redistribution of a secreted amastigote antigen in parasitized host cells. PMID- 7774607 TI - Thyroid radioiodide transport: models, rate-limiting steps, and relation to formation of iodoprotein. PMID- 7774608 TI - Endocytosis of decorin by bovine aortic endothelial cells. off. AB - The small dermatan sulfate proteoglycan decorin is efficiently internalized by a variety of cells of mesenchymal origin. Decorin-binding receptor proteins of 51 and 26 kDa are involved in this process. Uptake is modulated by highly sulfated heparan sulfate which interacts with the receptor proteins, too. Compared with cultured skin fibroblasts, bovine aortic endothelial cells have a lower capacity for decorin endocytosis whereas their apparent concentration of receptor proteins is even higher. The low internalization rate is attributed to the greater occupancy of receptor proteins by heparan sulfate of the plasma membrane and/or the extracellular matrix. Growth of endothelial cells on Falcon 3090 tissue culture inserts made possible to study decorin uptake from the apical and basolateral membrane, respectively. Decorin uptake was at the limit of detection when the proteoglycan was added to the basolateral compartment. Uptake via the apical membrane was at least as efficient as in monolayer cultures on plastic. The basolateral membrane, however, was enriched in receptor proteins, but also in heparan sulfate proteoglycans. It is, therefore, suggested that endothelial cells are especially involved in the clearance of decorin which is present in blood plasma. PMID- 7774609 TI - The microtubule cytoskeleton in human phagocytic leukocytes is a highly dynamic structure. AB - The microtubule cytoskeleton of human leukocytes has been difficult to study, in part, due to the lack of a reliable protocol for the indirect immunofluorescence staining of microtubules in these cells. We report here the development of a simple and reliable immunocytochemical labeling protocol for the examination of microtubules in leukocytes including monocytes, neutrophils, and eosinophils. The dynamic properties of microtubules in both monocytes and neutrophils were examined by indirect immunofluorescence staining of cells following exposure to nocodazole. Nocodazole-induced depolymerization is extremely rapid in both cell types, as is the regrowth of microtubules following removal of the nocodazole. Rapid reorganization of the microtubule cytoskeleton was also observed in neutrophils undergoing chemotactic stimulation. Bundling of microtubules was observed in both monocytes and neutrophils isolated from patients undergoing taxol infusion chemotherapy. The taxol-induced bundles were transient in nature as they were absent from samples collected 48 h following the completion of the taxol infusion. These results demonstrate the unique dynamic properties of leukocyte microtubules and indicate that they can be altered in vivo. The development of this staining protocol should allow for the further analysis of leukocyte microtubules as related to the normal functional response of these cells and form the basis for correlating alterations in microtubule dynamics with the effects of taxol on leukocyte function. PMID- 7774610 TI - A radioimmunoassay to monitor synaptic activity in hippocampal neurons in vitro. AB - Exocytosis of synaptic vesicles (SV) results in the surface exposure of lumenal epitopes of SV proteins. We have recently described the use of antibodies directed against the lumenal N-terminus of synaptotagmin I (Sytlum-Abs) to morphologically monitor exo-endocytic recycling of SVs. We report here that a radioimmunoassay based on these antibodies can be used to quantify levels of synaptic activity in primary neuronal cultures. High density cultures of hippocampal neurons grown in the absence of glia were used for these studies. A significant cell surface pool of synaptotagmin I immunoreactivity was detectable by Sytlum-Abs at steady state. The increase in the amount of Sytlum-Abs which became cell bound during a 3 min incubation at 37 degrees C over the Ab bound to this cell surface pool, was substantially higher in depolarizing media containing extracellular Ca2+ than in Ca(2+)-free media. Incubation of the cultures with Sytlum-Abs for longer time periods indicated a sustained increase in the rate of SV exocytosis in depolarizing media which lasted for at least 1 h. This increase was completely abolished by pretreating the neurons with tetanus toxin and this block correlated with a disappearance of synaptobrevin immunoreactivity. This radioimmunoassay therefore offers a new way to monitor SV exocytosis of neuronal populations in vitro irrespective of the type of neurotransmitter secreted and of postsynaptic effects. PMID- 7774611 TI - Basolateral but not apical application of protease results in a rapid rise of transepithelial electrical resistance and formation of aberrant tight junction strands in MDCK cells. AB - In the presence of Ca2+, application of trypsin to the basolateral surface of confluent MDCK cell monolayers with formed tight junctions (TJ), induces the formation of basolaterally oriented aberrant TJ strands. Induction of aberrant TJ strands is accompanied by an increase in transepithelial electrical resistance (TER), up to 90%, which upon addition of trypsin inhibitor is maintained for up to 1 h. Thereafter TER returns slowly to baseline values. Under similar conditions, application of trypsin to the apical surface has little or no effect on either TER or the number of aberrant TJ strands. Confocal microscopy of monolayers, immunostained for ZO-1, revealed that this TJ associated cytoplasmic protein, extended below the TJ along the basolateral surface following brief exposure to trypsin. Removing Ca2+ after treatment of the monolayer with basolaterally applied trypsin resulted, after 20 min, in the increased partitioning of TJ particles onto the E fracture face, of both normal and aberrant TJ strands. Like the TJ strands themselves, therefore, aberrant strands may be linked to cytoskeletal elements. Aberrant TJ strands do not form when monolayers, maintained in low Ca2+ medium, are exposed to trypsin, suggesting that under these conditions TJ precursors, and/or trypsin-sensitive proteins regulating TJ strand assembly, are sequestered in a vesicular compartment that is inaccessible to exogenous trypsin. Prolonged exposure of the apical surface of an established, polarized epithelium with intact TJ to trypsin, had little effect on TJ integrity and did not induce aberrant strands. PMID- 7774612 TI - Carbohydrate-deficient glycoprotein syndrome (CDGS)--glycosylation, folding and intracellular transport of newly synthesized glycoproteins. AB - Carbohydrate-deficient glycoprotein syndrome (CDGS) is a hereditary glycosylation disorder of unknown origin. In this study we used skin fibroblasts from patients with CDGS to study the glycosylation of three well characterized glycoproteins using gel mobility analysis, endoglycosidase treatments and protein folding studies. We show that glycoprotein transport along the secretory pathway was delayed. Dilation of the rough endoplasmic reticulum indicated a retention phenomenon for selected glycoproteins. However, for all examined glycoproteins cotranslational glycosylation in CDGS fibroblasts was normal. PMID- 7774614 TI - Glucose levels and succinate and lactate dehydrogenase activity in EMT6/Ro tumor spheroids. AB - To evaluate the effects of glucose on the development of cell heterogeneity and the occurrence of necrotic areas in the center of tumor spheroids, a procedure (combining microdissection of small tissue samples from frozen-dried cryosections and microchemical analysis) was developed to measure glucose in distinct, concentrically arranged, microregions of tumor spheroids: the outermost area of proliferating cells, the area of nonproliferating cells and 2 central "necrotic" areas, with either abundant or little intercellular space. Since glucose levels, for analytical reasons, had to be expressed on a dry weight basis, and because of the morphological heterogeneity of the microregions of tumor spheroids, it was necessary to measure and take into account the regional differences in cell density (water content), in order to obtain adequate estimates of the glucose levels in the various microregions. At glucose concentrations of 5.5 and 3.6 mM in the culture medium, the glucose levels varied between 3.5 and 1.4 mmoles/kg wet weight and were lowest in those central areas where the cell density was lowest. Histochemical demonstration of the distribution of lactate and succinate dehydrogenase activity indicates a considerably higher capacity of tumor cells for anaerobic than for aerobic energy production. PMID- 7774613 TI - Yeast Nop3p has structural and functional similarities to mammalian pre-mRNA binding proteins. AB - Indirect immunofluorescence shows the yeast protein Nop3p/Np13p/Mts1p to be localized both in the nucleoplasm and the nucleolus. Here we show that Nop3p can be efficiently UV cross-linked in vivo to poly(A)+ RNA. In higher eukaryotes it would therefore be classed as a heterogeneous nuclear ribonucleoprotein (hnRNP) component. As judged by immunofluorescence and in situ hybridization, a temperature-sensitive allele of nop3 leads to the accumulation of poly(A)+ RNA in the nucleus at non-permissive temperature. The sequence of Nop3p shows homology to the larger members of the SR protein family of splicing factors, particularly in the RRMH domain. We have, however, detected no splicing defects in strains genetically depleted to Nop3p or carrying a temperature-sensitive allele. PMID- 7774615 TI - International Congress on Sudden Infant Death Syndrome: The Role of Environmental Factors in Infant Morbidity and Mortality. Graz, Austria, 24-27 May 1995. Abstracts. PMID- 7774616 TI - 29th Annual meeting of the European Society for Clinical Investigation and the Medical Research Society of Great Britain. Cambridge, England, 2-5 April 1995. Abstracts. PMID- 7774618 TI - T cells made deficient in interleukin-2 production by exposure to staphylococcal enterotoxin B in vivo are primed for interferon-gamma and interleukin-10 secretion. AB - The superantigen staphylococcal enterotoxin B (SEB) induces a defect in interleukin (IL)-2 production by T cells expressing specific T cell receptor V beta domains. The present study was undertaken to determine the capacity of T cells, made deficient in IL-2 production by exposure to SEB in vivo, to secrete interferon (IFN)-gamma and IL-10 and to induce pathology upon SEB rechallenge. For this purpose, BALB/c mice received two intraperitoneal injections of 100 micrograms SEB with a 48-h interval. First, we compared peak serum levels of IL 2, IFN-gamma and IL-10 after SEB rechallenge with those measured after a single SEB injection in control mice. The expected defect in IL-2 production in SEB pretreated mice was associated with a major increase in IL-10 and IFN-gamma levels which were about fivefold higher than in controls. Experiments in mice depleted of CD4+ or CD8+ cells as well as studies in which purified T cell populations were rechallenged with SEB in vitro indicated that both CD4+ and CD8+ cells from SEB-pretreated mice were primed for IL-10 and IFN-gamma production. Furthermore, SEB-pretreated mice were sensitized to the toxic effects of the superantigen as indicated by a 30-70% lethality rate (vs. 0% in naive mice) within 48 h after SEB rechallenge. IFN-gamma was involved in the lethal syndrome as it could be prevented by injection of neutralizing anti-IFN-gamma monoclonal antibody. We conclude that SEB-reactive T cells made deficient for the production of IL-2 by exposure to SEB in vivo are primed for IFN-gamma and IL-10 production, and that IFN-gamma up-regulation is involved in the shock syndrome occurring upon SEB rechallenge. PMID- 7774617 TI - RAG1 and RAG2 expression in human intestinal epithelium: evidence of extrathymic T cell differentiation. AB - We examined the hypothesis that the adult human gastrointestinal tract is a site of extrathymic T cell differentiation. When T lymphocytes undergo gene rearrangement, the products of both RAG1 and RAG2 genes are expressed; RAG mRNA is present only in tissue governing lymphocyte maturation. In this study, reverse transcription polymerase chain reaction (RT-PCR) was used to detect RAG1-and RAG2 specific mRNA. Total RNA was purified from small intestinal samples from five adults. Peripheral blood mRNA from the same patient was used as a negative control in two cases. Bone marrow RNA preparations from two healthy donors were used as positive controls. cDNA synthesis was carried out using random hexamers. Primers for first round and nested PCR of RAG1 and RAG2 were synthesized. RAG1 and RAG2 mRNA was detected in all bone marrow preparations but was absent in all peripheral blood samples. RAG1 and RAG2 mRNA was detected in the small intestine of four of the five patients studied. RAG1 and RAG2 expression was localized in the epithelial layer and absent in the lamina propria. RAG1 and RAG2 expression in the epithelial layer is strong evidence that T cell differentiation occurs in the adult human intestine. PMID- 7774619 TI - Expression of heat-stable antigen on tumor cells provides co-stimulation for tumor-specific T cell proliferation and cytotoxicity in mice. AB - Heat-stable antigen (HSA/J11d/possibly homologous to CD24), a cell adhesion molecule capable of providing a co-stimulatory signal for T cell proliferation, is expressed on B cells, activated T cells, monocytes, granulocytes, Langerhans cells and thymocytes. Recent studies have demonstrated that co-stimulatory signals provided by cell adhesion molecules such as B7-1 play an essential role in generation of an anti-tumor immune response. To examine whether the co stimulatory signal provided by HSA can induce an anti-tumor immune response, we have transfected HSA cDNA into the murine melanoma cell line K1735M2, and examined the ability of this transfected cell line to induce tumor-specific T cell responses. The results demonstrate that spleen cells from mice immunized with HSA-transfected K1735M2 cells showed enhanced T cell proliferation in a mixed lymphocyte tumor reaction (MLTR) assay and also demonstrated a significant anti-tumor cytotoxicity to the parent tumor cell (K1735M2). This anti-tumor cytolytic activity could be abrogated by pretreatment of effector cells with anti mouse CD8 monoclonal antibody and complement. Under similar conditions, spleen cells from C3H mice immunized with vector-transfected K1735M2 cells neither actively proliferate in an MLTR assay, nor did they exert significant cytolytic activity against the respective tumor cells. In summary, our study demonstrated that HSA can provide a co-stimulatory signal for the T cell immune response against tumor cells in a murine model. PMID- 7774620 TI - Evidence for the stochastic acquisition of cytokine profile by CD4+ T cells activated in a T helper type 2-like response in vivo. AB - The diversity of cytokine production patterns displayed by T cells activated in vivo was investigated by analyzing short-term antigen-specific CD4+ T cell clones and single CD4+ T cells derived from draining lymph nodes of mice undergoing a T helper 2 (Th2)-like response to keyhole limpet hemocyanin (KLH). On average, 2.7% of CD4+ lymph node cells gave rise to clones in the presence of the immunizing antigen and, of these, about 90% secreted interleukin-4 (IL-4) and 20% secreted interferon-gamma (IFN-gamma) when restimulated after 2 weeks in vitro. Almost all IFN-gamma-producing clones co-produced IL-4. The definition of clones as positive or negative for cytokine synthesis depended on assay sensitivity, however, since their titers were distributed continuously from the threshold of detection over at least a 1000-fold range. Reverse-transcription polymerase chain reaction analysis of 59 clones revealed multiple patterns of co-expression of IL-2, IL-3, IL-4, IL-6, IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM CSF) mRNA. Although most clones contained detectable IL-4 and IL-6 mRNA and a minority contained IFN-gamma mRNA, only 1 clone expressed the canonical Th2 cytokine profile. The observed frequencies of mRNA co-expression for most of the six cytokines (including IL-4 with IFN-gamma), and the frequency of co-secretion of IL-4 and IFN-gamma, were not significantly different from those predicted for random association. Independent regulation of IL-4 and IFN-gamma mRNA expression was confirmed at the single-cell level in a polyclonal population of KLH-primed CD4+ cells, among which co-expression of these cytokines again occurred at the frequency predicted for a random event. The data suggest that the polarization of this immune response towards a Th2 cytokine profile is achieved by altering the probabilities of expression of the IL-4, IFN-gamma and other cytokine genes at the population level, rather than by selective expansion of a distinct T cell subset. PMID- 7774621 TI - Biphasic effect of interferon-gamma in murine collagen-induced arthritis. AB - Interferon-gamma (IFN-gamma) exerts both enhancing and suppressing influences on collagen-induced arthritis (CIA), depending on the route and protocol of administration. To study the role of IFN-gamma on the autoimmune process of CIA, we treated DBA/1 mice with two different rat monoclonal antibodies (mAb) to murine IFN-gamma. Treatments, given twice weekly for 4 weeks, consisted of intraperitoneal injections of either mAb. In early treatments, starting from the day of immunization with type II collagen (CII), the severity of arthritis was reduced in both groups of anti-IFN-gamma-treated mice compared with control groups. Moreover, anti-CII antibody levels decreased in the sera of these mice. CIA was also down-regulated in mice treated from days 14 or 28 post immunization. In contrast, late treatments with anti-IFN-gamma mAb either induced aggravating effects, or did not affect the course of the disease. On the other hand, administration of high doses (8 x 10(4) U three times/week) of rat recombinant IFN-gamma exerted a transient increase of CIA severity. These findings suggest that IFN-gamma may play a critical role during both the induction and the course of CIA, first enhancing the immune response, and then regulating the arthritis process. PMID- 7774623 TI - Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo. AB - Lymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well-known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 +/- 5.0% vs. 40.6 +/- 11.0%, T lymphocytes 84.6 +/- 6.3% vs. 56.5 +/- 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 +/- 0.9% vs. 8.9 +/- 3.6%), whereas that in HEV of axLN (19.0 +/- 6.4% vs. 16.6 +/- 6.0%) and PP (30.6 +/- 6.1% vs. 33.9 +/- 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo. PMID- 7774622 TI - Depletion of CD8+ T cells suppresses the development of experimental autoimmune myasthenia gravis in Lewis rats. AB - To understand the role of CD8+ T cells in experimental autoimmune myasthenia gravis (EAMG), CD8+ T cells were depleted by injecting a monoclonal anti-rat CD8 antibody (OX8) into Lewis rats immunized with Torpedo acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA). CD8-depleted EAMG rats showed strikingly less muscle weakness and lower anti-AChR IgG antibody levels compared to Hy2-15-injected control EAMG rats. Moreover, the numbers of AChR-specific IgG antibody-secreting cells, AChR-reactive interferon-gamma-secreting T helper type 1-like cells and lymphocyte proliferation to AChR were lower in the CD8-depleted group than in control EAMG rats. These differences were significant among mononuclear cells from inguinal and popliteal lymph nodes, mesenteric lymph nodes and spleen, but not from thymus when examined 3, 5 and 7 weeks post-immunization. We suggest that CD8+ T cells are involved in the induction and persistance of EAMG by directly or indirectly affecting AChR-reactive T cells and anti-AChR IgG antibody-secreting cells. PMID- 7774625 TI - Substitutions at the Glu62 residue of human interleukin-2 differentially affect its binding to the alpha chain and the beta gamma complex of the interleukin-2 receptor. AB - Human interleukin-2 (IL-2) alpha helix B is more conserved than the whole molecule, but has been less studied than other alpha helices of IL-2. Using site directed mutagenesis, several IL-2 mutants in this helix were obtained. We found that the IL-2 mutant containing Leu at position 62 (Leu62-IL-2) loses its ability to bind IL-2 receptor subunit alpha (IL-2R alpha), but retains binding affinity to IL-2R subunit beta gamma as well as some bioactivity; nevertheless, another substitution at the same residue, Arg62IL-2, loses its binding ability to both IL 2R alpha and IL-2R beta gamma, and can no longer stimulate IL-2-dependent cell growth, showing that Glu62 not only takes part in IL-2R alpha binding, but can also affect IL-2 binding to IL-2R beta gamma. In this regard, Glu62 may be a key site in the IL-2/IL-2R alpha interaction, and can facilitate IL-2R ternary complex formation, leading to IL-2R alpha-mediated, IL-2-stimulated signal transduction. PMID- 7774624 TI - Generation of antigen-specific CD4+ T cell lines from naive precursors. AB - The conditions required for sensitizing naive T cells to nominal antigen are poorly understood. In this report we describe an in vitro system for generating antigen-specific CD4+ T cells from previously unprimed individuals. Freshly isolated CD4+ T cells were cultured with keyhole limpet hemocyanin (KLH), sperm whale myoglobin (SWM), or human immunodeficiency virus (HIV) gp160, antigens to which most persons have not been sensitized, in the presence of either dendritic cells (DC) or macrophages (M phi). In short-term (< 8 days) cultures, CD4+ T cells or their CD4+, CD45RA (naive) subpopulation mounted significant proliferative responses to KLH, SWM, and HIV gp160, but only if the antigens were presented by DC. In contrast, CD4+, CD45RO (memory) T cells responded poorly to these antigens, although they responded vigorously to tetanus toxoid, a recall antigen, presented by either DC or M phi. KLH- and SWM-specific CD4+ T cell lines were established from the starting population that had been sensitized in vitro, following repeated stimulation with antigen and M phi in medium supplemented with interleukin-2 and interleukin-4. Despite the continued presence of these cytokines during T cell expansion, the expanded lines retained their ability to respond to the priming antigen in the absence of exogenous cytokines. When the CD45RA and CD45RO subpopulations were sensitized and expanded separately, the CD45RA cells alone gave rise to antigen-specific T cell lines, while the CD45RO cells proliferated nonspecifically. These results demonstrate that human naive CD4+ T cells can be sensitized in vitro to nominal antigens presented by DC and that the sensitized cells can be expanded into long-term lines that retain their antigen specificity. PMID- 7774626 TI - Homotypic aggregation of murine B lymphocytes is independent of CD23. AB - CD23 is a low-affinity receptor for IgE (Fc epsilon RII). Functions attributed to CD23 not involving IgE suggest that it interacts with ligands other than IgE. CD21 has recently been described as a counter ligand for CD23. A number of lines of evidence have implicated CD23 as an adhesion molecule in human B cells. We have investigated the role of CD23 in homotypic B cell aggregation in the mouse, using lipopolysaccharide plus interleukin-4-induced aggregation as a model system. In this system high levels of aggregation are accompanied by a massive up regulation of CD23 expression. However, in contrast to what has been observed in human B cells, we find no evidence of a role for CD23 in homotypic adhesion of murine B cells. PMID- 7774627 TI - Alloreactive natural killer cells in the rat: complex genetics of major histocompatibility complex control. AB - A major role for the nonclassical major histocompatibility complex (MHC) class I region, i.e. RT1.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several findings suggested the existence of NK triggering alloantigens coded for by this region. Here, we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A activated T cell blasts by comparing semi-syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti-F1 hybrid cytolytic activities of parental strain NK cells were measured, both recessively and non recessively inherited susceptibility patterns emerged. (c) In most combinations parental strain cells were lysed by F1 hybrid NK cells, thus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non-recessively, i.e. when parent anti-F1 reactivity was detected, than in recessive combinations. (d) LEW.1LM1 (RT1lm1) target cells, with a deletion in the RT1.C region that includes expressed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.1L(LEW), RT1l) than were parental LEW (RT1l) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1c, RT1u) as well as semi syngeneic (RT1l/c) NK cells were employed, i.e. sensitivity was decreased. We conclude that certain MHC-encoded antigens, depending on the haplotype combination of effector and target cells, may either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed. PMID- 7774628 TI - Regulation of T cell receptor (TCR)-beta locus allelic exclusion and initiation of TCR-alpha locus rearrangement in immature thymocytes by signaling through the CD3 complex. AB - During thymocyte differentiation, the T cell receptor (TCR)-beta genes are rearranged before the TCR-alpha genes. Immature CD4-8- double-negative thymocytes with a productive rearrangement of the TCR-beta locus are selected to continue maturation to the CD4+8+ double-positive stage, driven by signals through the pre TCR. The signals through the pre-TCR can be synchronized by injection of mice with anti-CD3 epsilon monoclonal antibody. Using this approach, we demonstrated coordinated induction of a triad of responses in immature thymocytes: arrest of V to DJ rearrangement in the TCR-beta locus, transient down-regulation of rearrangement-activating gene (RAG)-1 and RAG-2 transcripts, and initiation of germ-line transcription of the TCR-alpha locus. These results suggest that the transition from TCR-beta to TCR-alpha locus rearrangement is controlled by signal transduction through the pre-TCR. PMID- 7774629 TI - Soluble mouse major histocompatibility complex class II molecules produced in Drosophila cells. AB - We have exploited Drosophila melanogaster Schneider cells and compatible inducible expression vectors to produce large amounts of secreted major histocompatibility complex (MHC) class II molecules (I-Ed). A simple two-step purification protocol was developed. In the first step, recombinant molecules were enriched using a monoclonal anti-class II antibody column followed by a nickel chelate column which further purified and concentrated the recombinant protein to several mg/ml. Characterization of the purified material indicates that the molecules are correctly assembled into alpha beta heterodimers. Further analysis shows that the recombinant MHC class II molecules are devoid of endogenous peptides and, therefore, homogeneous peptide/MHC complexes could be prepared by adding exogenous I-Ed-specific peptides at slightly acidic pH. Upon peptide addition, molecules underwent a conformational change into a more compact form revealed by gel filtration analysis. In addition, the peptide/MHC complexes were biologically active. As little as 10 ng of these complexes coated on plastic from a 100 ng/ml solution were sufficient to trigger antigen-specific T cell hybridomas. These MHC class II molecules, together with various forms of soluble T cell receptor (TcR) proteins, provide valuable tools to analyze the molecular details of TcR/antigen recognition. PMID- 7774630 TI - Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin). AB - We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL 1ra) and IL-8 in cultures of normal human monocytes. The addition of IVIg to cultures of purified monocytes induced a dose-dependent secretion of IL-1ra and IL-8 without stimulating the production of IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha or IL-6. The effects of IVIg required both the Fc and F(ab')2 portions of IgG. IVIg-induced production of IL-8 by monocytes was enhanced by lipopolysaccharide (LPS), although LPS inhibited the secretion of IL-1ra, suggesting that IVIg and LPS stimulate distinct intracellular pathways in monocytes. Induction of IL-1ra and IL-8 by IVIg was enhanced in the presence of autologous T lymphocytes. Our observations document the selectivity of the effects of IVIg on the synthesis of cytokines and cytokine antagonists by human monocytes. Induction of IL-1ra and IL-8 by IVIg may contribute to the anti inflammatory effects of immunoglobulin therapy in patients with autoimmune and systemic inflammatory disorders. PMID- 7774631 TI - Inhibition of natural killer cell-mediated bone marrow graft rejection by allogeneic major histocompatibility complex class I, but not class II molecules. AB - The role of major histocompatibility complex (MHC) class I and class II molecules in natural killer (NK) cell-mediated rejection of allogeneic, semisyngeneic and MHC-matched bone marrow grafts was investigated. The use of beta 2-microglobulin (beta 2m) -/- and beta 2m +/- mice as bone marrow donors to MHC-mismatched recipients allowed an analysis of whether the presence of semi-syngeneic and allogeneic MHC class I gene products would be triggering, protective or neutral, in relation to NK cell-mediated rejection. Loss of beta 2m did not allow H-2b bone marrow cells to escape from NK cell-mediated rejection in allogeneic (BALB/c) or semi-allogeneic (H-2Dd transgenic C57BL/6) mice. On the contrary, it led to stronger rejection, as reflected by the inability of a larger bone marrow cell inoculum to overcome rejection by the H-2-mismatched recipients. In H-2 matched recipients, loss of beta 2m in the graft led to a switch from engraftment to rejection. At the recipient level, loss of beta 2m led to loss of the capability to reject H-2-matched beta 2m-deficient as well as allogeneic grafts. When MHC class II-deficient mice were used as donors, the response was the same as that against donors of normal MHC phenotype: allogeneic and semi-syngeneic grafts were rejected by NK cells, while syngeneic grafts were accepted. These data suggest a model in which allogeneic class I molecules on the target cell offer partial protection, while certain syngeneic class I molecules give full protection from NK cell-mediated rejection of bone marrow cells. There was no evidence for a role of MHC class II molecules in this system. PMID- 7774632 TI - Orally induced bystander suppression in experimental autoimmune uveoretinitis occurs only in the periphery and not in the eye. AB - Oral administration of retinal soluble antigen (S-Ag) suppresses the induction of S-Ag-mediated experimental autoimmune uveitis (EAU) in Lewis rats. EAU induced with interphotoreceptor retinoid-binding protein (IRBP), another retinal autoantigen, can also be suppressed by oral administration of IRBP. It has been speculated that feeding with one retinal autoantigen could suppress induction of uveitis with the other retinal protein by means of bystander suppression. Both uveitogenic effector and suppressor cells should find their antigens within the retina, where the suppressor cells would be expected to act on the effector cells. However, reciprocal combinations of antigens used for induction and suppression of uveitis failed to prevent onset of disease, demonstrating that bystander suppression obviously does not occur in the eye. To investigate further the localization of suppressor mechanisms, we fed Lewis rats either with retinal S-Ag or with ovalbumin (OVA) and then immunized the animals either with a mixture of S-Ag and OVA or with each antigen separately, injected into contralateral hind legs. Feeding of S-Ag prior to immunization led to suppression of uveitis, whereas feeding of OVA had no tolerizing effect when S-Ag and OVA were injected into different legs. Nevertheless, immunizing rats with a mixture of S-Ag and OVA after OVA feeding suppressed uveitis to a high degree. These findings suggest that orally induced bystander suppression might not occur in the target organ, but rather peripherally at the site of induction of the autoimmune T cells. PMID- 7774633 TI - Toxoplasma gondii-specific CD4+ T cell clones from healthy, latently infected humans display a Th0 profile of cytokine secretion. AB - Human Toxoplasma gondii (Tg)-specific T cell clones were raised by infecting peripheral blood mononuclear cells (MNC) from two healthy, latently infected individuals with Tg trophozoites. All of the clones had a CD4+ immunophenotype and produced simultaneously interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5 upon mitogen or antigen stimulation. Tg-specific T cell clones were classified as T helper of type 0 (Th0) since most of them released roughly comparable amounts of IFN-gamma and IL-4. In some clones, a trend to an increased production of IFN-gamma following antigen-specific as compared to non-specific stimulation was observed. The Th0 phenotype was also expressed by T cell clones that had been raised from bulk cultures performed in the presence of IL-4 or IFN gamma. All of the Tg-specific T cell clones were cytolytic in a non-specific assay which involves the triggering of the CD3-T cell receptor (TcR) complex. Some clones specifically lysed an autologous lymphoblastoid cell line (LCL) that had been infected with Tg trophozoites. Finally, most of the Tg-specific T cell clones produced IL-10, irrespective of whether they had been raised from bulk cultures incubated in the presence or absence of IL-4 or IFN-gamma. Taken together, these findings suggest that Tg-specific Th0 helper cell clones from healthy, latently infected individuals, beside activating toxoplasmacidal mechanisms through IFN-gamma release, might limit the magnitude of the immune response of the parasite by killing Tg-infected antigen-presenting cells and by releasing IL-10. PMID- 7774634 TI - T lymphocyte development in p56lck deficient mice: allelic exclusion of the TcR beta locus is incomplete but thymocyte development is not restored by TcR beta or TcR alpha beta transgenes. AB - The protein tyrosine kinase, p56lck, is involved in signal transduction in mature T cells and in the molecular events controlling early thymocyte differentiation. Thymuses of mice deficient for p56lck expression (p56lck-/-) consist of immature CD4-CD8- double-negative (DN) and CD4+CD8+ double-positive (DP) thymocytes and are severely reduced in total cell number. In this report we have studied DN thymocytes from p56lck-/- mice and found an increase in the proportion of the CD44-CD25+ subset, suggesting that transit through this stage, which is known to require T cell receptor (TcR) beta expression, may be delayed in the absence of p56lck expression. In addition, the expression of a transgenic TcR beta chain or TcR alpha beta pair did not restore thymic development in p56lck-/- mice. However, in contrast to mice expressing a dominant negative isoform of p56lck in which DP thymocytes do not develop, DP thymocytes still develop in nontransgenic and TcR transgenic p56lck-/- mice. These results demonstrate that expansion of the DP subset is impaired in p56lck-/- mice. In contrast, allelic exclusion is not severely compromised. Although there was an increase in the number of peripheral T cells expressing more than one V beta chain in TcR transgenic p56lck /- mice, we found that inhibition of endogenous TcR beta gene rearrangement was almost complete in thymocytes of V beta transgenic p56lck-/- mice and we could not detect any peripheral T cells that expressed more than one V beta chain in non-transgenic p56lck-/- mice. PMID- 7774635 TI - Down-regulation of class II major histocompatibility complex molecules on antigen presenting cells after interaction with helper T cells. AB - The recognition of antigenic peptides by CD4+ helper T cells is demonstrated here to result in a dramatic (up to 90%) decrease in expression of major histocompatibility complex (MHC) class II molecules on the surface of antigen presenting cells (APC). The reduction is selective to the class II isotype presenting the antigen, but if affects both allelic forms of the same isotype in heterozygous APC. The observed MHC down-regulation requires a specific T cell receptor-peptide-class II interaction, a direct contact between T cell and APC, and the involvement of CD2 molecules. These findings have important implications for the regulation of immune response, self tolerance, and autoimmunity. PMID- 7774636 TI - An interleukin-6 transgene expressed in B lymphocyte lineage cells overcomes the T cell-dependent establishment of normal levels of switched immunoglobulin isotypes. AB - Long-term proliferating, stromal cell/interleukin (IL)-7-reactive precursor B cell lines established from fetal liver and bone marrow of human IL-6-transgenic B6Ld46 mice produce and secrete human IL-6. When transplanted into severe combined immunodeficient (SCID) or Rag2 knockout (Rag2-T) mice, these pre-B-cell lines establish a part of the B cell compartment but yield no T cells, as do pre B cell lines from genetically matched non-transgenic mice. Within 2 to 3 months after transplantation, the serum of mice transplanted with pre-B cells from normal mice contains normal levels of IgM (200-600 micrograms/ml) but 10-100-fold lower levels of the IgG subclasses and of IgA. In contrast, the sera of mice transplanted with IL-6 transgenic pre-B cells contain not only IgM, but also IgG and IgA at nearly normal levels. The results indicate that at least a part of the plasmacytosis and elevated IgG production observed previously in the IL-6 transgenic mice appears to be due to a T cell-independent activation of IgG and IgA production by the IL-6-secreting pre-B cells and their differentiated progeny in the immunodeficient hosts. PMID- 7774637 TI - Signaling through murine CD38 is impaired in antigen receptor-unresponsive B cells. AB - CD38 is a 42-kDa membrane associated enzyme which converts NAD into cyclic ADP ribose (cADPR), a Ca(2+)-mobilizing second messenger, and ADP-ribose (ADPR). Agonistic antibodies to murine CD38 deliver a potent growth co-stimulus to mature splenic B lymphocytes. In this report we demonstrate a striking relationship between CD38-mediated mitogenesis and the ability of surface IgM to promote B cell proliferation. Tolerized B lymphocytes obtained from a double-transgenic mouse model of B cell tolerance do not proliferate in response to antigen stimulation through the Ig receptor or to agonistic anti-CD38 antibodies. Similarly, B-1 cells isolated from the peritoneal cavity of normal mice, and splenic B cells isolated from newborn mice were also unresponsive to both anti IgM and anti-CD38 stimulation. All of these CD38-unresponsive B cells expressed normal levels of cell surface CD38 and responded to numerous other stimuli. CD38 immunoprecipitated from these B cell populations was normal in size and effectively hydrolyzed NAD, suggesting that the defect in CD38 signaling likely occurs downstream of CD38 itself. Signaling through CD38 and IgM does not always have identical effects on B cells since anti-CD38 cannot deliver inhibitory growth or differentiation signals to normal B cells or immature B cell lines. Nevertheless, the correlative data with these multiple B cell models of unresponsiveness suggests that the signaling pathway utilized by CD38 and IgM intersect, possibly sharing at least one of the crucial components of the Ig receptor signaling cascade. PMID- 7774638 TI - Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells. AB - Glucocorticoids (GC) are known to inhibit the proliferative response of leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. However, GC are frequently administered to human fetuses and newborns for the prevention and treatment of respiratory distress syndrome. The immune system of human newborns is still a functionally immature system. Therefore, we wondered whether the immaturity is also reflected by altered responses to hormonal signals such as glucocorticoids. We studied the effects of the GC dexamethasone (DEX) on the proliferation of peripheral blood mononuclear cells and T cells in vitro after stimulation with phytohemagglutinin, anti-CD3, anti-CD3/anti-CD28 or anti-CD2/anti-CD28. Our data demonstrate that neonatal cells are much more sensitive to inhibition of the proliferative response by DEX than adult cells (ED50 1 +/- 0.8 nM vs. 221 +/- 135 nM). This difference in sensitivity is not related to differences in affinity and capacity of binding of [3H] DEX. Moreover, we show that the mechanisms of GC inhibition differ between adult and neonatal cells. In adult cells, addition of interleukin (IL)-2 does not restore DEX inhibition of the proliferative response. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2. These data suggest that the primary target of GC in neonatal cells is inhibition of IL-2 production. In adult cells, other mechanisms are responsible for inhibition of T cell proliferation. PMID- 7774639 TI - Studies on the T cell dependence of natural IgM and IgG antibody repertoires in adult mice. AB - The present experiments address the thymic dependence of IgM and IgG natural antibody repertoires in adult euthymic and athymic BALB/c mice, as well as in athymic animals reconstituted with a fixed number of syngeneic T cells. Within 3 weeks of the transfer of 10(7) syngeneic splenic T lymphocytes to athymic mice, the T cell compartment is essentially reconstituted in the peritoneal cavity (up to 80% of the numbers in euthymic animals), but is only 10-20% of controls in the spleen and lymph nodes. Early after transfer, there is an increase in the numbers of activated B cells and of immunoglobulin-secreting cells in the spleen, and within 1-2 weeks, the serum concentrations of IgG1 and IgG2a are fully reconstituted to control levels (30-40-fold increased). Multiparametric analyses of serum IgM and IgG repertoires revealed that euthymic and athymic mice share essentially all natural antibody reactivities towards syngeneic extracts of liver and muscle. When tested at the same immunoglobulin concentrations, however, nude sera consistently show higher values of reactivity in all detectable bands. The transfer of 10(7) splenic T cells into athymic mice results in a general decrease of serum IgM reactivities, some of which become undetectable, and in alterations of the serum IgG repertoire as early as 1 week, and for at least 4 weeks after transfer. T cell transfer, however, fails to restore the euthymic IgM and IgG repertoires within 4 weeks. The present observations demonstrate that, after limited T cell reconstitution of nude mice, there is a rapid and quantitatively important increase of serum IgG1 and IgG2a production; the serum IgM reactivity repertoire is qualitatively similar in euthymic and athymic animals, but is generally decreased by T cell activity; and the serum IgG repertoire, which is qualitatively similar in euthymic and athymic animals, is amplified by T cell activity and partially altered by T cell transfer into athymic animals. These results raise questions on the mechanisms of B cell activation and natural antibody repertoire selection in T cell-deficient adult individuals. PMID- 7774640 TI - Human eosinophil peroxidase enhances tumor necrosis factor and hydrogen peroxide release by human monocyte-derived macrophages. AB - Inhibition of growth or eradication of experimentally induced tumors has been shown to be accompanied by infiltration of eosinophils and macrophages into the tumor mass. Since macrophages are important mediators of host antitumor activity, the possibility arises that a collaboration may exist between these two cell types in the control of tumor growth. In this study, we report the effect of eosinophil peroxidase (EPO), a basic protein contained in eosinophils that binds to several cell types including macrophages, on tumor necrosis factor (TNF) production and hydrogen peroxide release by human monocyte-derived macrophages. After incubation with EPO, the macrophages produced large amounts of TNF and displayed an enhanced phorbol 12-myristate 13-acetate-triggered hydrogen peroxide release. These effects were accompanied by an increased cell protein content and by morphologic changes leading the large, round macrophages of the control cultures to become elongated, pear-like or spindle shaped cells after treatment with EPO. The stimulatory effect of EPO on hydrogen peroxide release was insensitive to addition of exogenous catalase, a H2O2-degrading enzyme, suggesting that an extracellular catalytic activity of EPO was not involved. In addition, myeloperoxidase, the homologous peroxidase of neutrophils with a catalytic activity similar to that of EPO, was ineffective. The EPO-induced effects differed in several aspects from the effects of lipopolysaccaride and interferon-gamma, two well-known macrophage activators. These findings provide supportive evidence for a functional interrelationship between eosinophils and macrophages that may be physiologically relevant in the tumoricidal activity of macrophages. PMID- 7774641 TI - Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. AB - Group I Burkitt lymphoma (BL) lines retaining the original BL tumor cell phenotype are unable to present endogenously expressed antigens to HLA class I restricted cytotoxic T cells (CTL) but can be recognized if the relevant HLA class I/peptide epitope complex is reconstituted at the cell surface by exogenous addition of synthetic target peptide. Endogenous antigen-processing function is restored in BL lines that have undergone Epstein-Barr virus (EBV)-induced drift in culture to the group III phenotype typically displayed by EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA-class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)-2, lmp-7 and delta, although the mb-1 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter-associated proteins (Tap), with down-regulation of Tap-1 and Tap-2 in 8/8 and 7/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap-deficient T2 processing-mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus-encoded latent membrane protein-1 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up-regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen-processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon-gamma treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen-processing function of BL cells, and suggest that the accessibility of other EBV-associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status. PMID- 7774642 TI - Oral tolerance to haptens: intestinal epithelial cells from 2,4 dinitrochlorobenzene-fed mice inhibit hapten-specific T cell activation in vitro. AB - The mechanisms underlying the induction of immunological tolerance after feeding soluble exogenous antigens, including proteins and haptens, are still unclear. Using a model of oral tolerance to the contact-sensitizing hapten 2,4 dinitrochlorobenzene (DNCB), we have compared the ability-of intestinal epithelial cells and of Peyer's patch APC to present DNCB in vitro or ex vivo after oral feeding, to specific peripheral lymph node T cells from DNCB sensitized mice. In contrast to Peyer's patch APC, which induce efficient hapten specific T cell activation upon exposure to the hapten either in vitro or in vivo, mature MHC class-II-positive intestinal epithelial cells were unable to induce T cell activation in either case. Interestingly, enterocytes from DNCB-fed mice exerted a dramatic inhibitory effect on the proliferative response of hapten primed T cells in response to dinitrobenzene sulfonate presented by syngeneic spleen cells. This inhibitory effect, which was also observed with supernatant of intestinal epithelial cells from DNCB-fed mice, could be reversed by neutralizing anti-transforming growth factor (TGF)-beta antibodies. In addition, pre incubation of hapten-sensitized T cells with enterocytes from DNCB-fed mice induced T cell anergy, which could be reversed by exogenous interleukin-2 or interleukin-4. These data demonstrate that intestinal epithelial cells activated in vivo by oral administration of DNCB are able to block proliferation of activated T cells through secretion of immunosuppressive cytokines such as TGF beta. It is proposed that intestinal epithelial cells may play a significant role in oral tolerance by limiting T cell-mediated hypersensitivity responses. PMID- 7774643 TI - Abnormal CD45RC expression and elevated CD45 protein tyrosine phosphatase activity in LEC rat peripheral CD4+ T cells. AB - LEC rats are known to show a maturational arrest in the development of CD4+8+ to CD4+8- cells in the thymus. Despite the blockade of maturation of CD4+8 thymocytes, CD4+ T cells were observed in peripheral lymphoid organs, and these cells exhibit a defect in interleukin-2 (IL-2) production upon concanavalin A (Con A) stimulation. Although peripheral CD4+ cells in normal rat highly expressed CD45RC (CD45RChigh), the level of CD45RC expression was low (CD45RClow) in LEC rat peripheral CD4+ cells. However, CD4+ cells from both strains highly expressed CD45 when those cells were stained by pan-CD45 mAb, suggesting that LEC rat CD4+ cells are deficient in expression of the CD45RC isoform, but not of CD45 molecules. When backcross rats from (F344 x LEC)F1 x LEC were examined, the phenotype for CD45 expression pattern in CD4+ cells was clearly correlated with IL-2 production level in response to Con A stimulation. Thus, CD45RClow cells exhibit a defect in IL-2 production, while CD45RChigh cells show normal IL-2 production. Protein tyrosine phosphatase (PTPase) activity in the membrane fraction of LEC rat CD4+ cells was threefold higher than that of normal rat CD4+ cells. Con A stimulation led to an increase in tyrosine phosphorylation levels, especially 100- and 40-kDa proteins, in normal rat CD4+ cells. In LEC rat CD4+ cells, however, the level of tyrosine phosphorylation in those proteins were very low. These results suggest that an elevated CD45 PTPase activity is responsive for a defect in IL-2 production in LEC rat peripheral CD4+ T cells. PMID- 7774644 TI - T cell receptor iota an alternatively spliced product of the T cell receptor zeta gene. AB - It has been previously suggested that three alternative splicings of the murine T cell receptor (TCR) zeta gene are involved in the regulation of TCR/CD3 transduction signals. We here describe a new alternative splicing of this gene (TCR iota), cloned by reverse transcriptase-polymerase chain reaction, that is encoded by exons 1-7 and 10. The protein putatively encoded by TCR iota mRNA differs in its carboxy terminus from that coded by TCR0 as a consequence of the reading frame shift of exon 10. The possible role of this new splicing in TCR modulation is briefly discussed. PMID- 7774646 TI - Antibody responses to Toxoplasma gondii antigen in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient mice reproduce the immunological status of the lymphocyte donor. AB - These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient (PBL-SCID) mice following vaccination with antigen from the protozoan parasite Toxoplasma gondii. To determine the effect of previous exposure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a single T. gondii-seronegative or a single seropositive donor. These reconstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicles as an immunological adjuvant. Animals were bled at pre-determined time points post vaccination and the expression of human anti-STAg antibodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both groups of reconstituted animals, although the pattern of isotype production differed markedly between groups. The response in animals reconstituted with lymphocytes from the T. gondii-seronegative donor consisted primarily of IgM and subsequently of IgG (predominantly IgG1). In animals reconstituted with lymphocytes from the seropositive donor, no parasite specific IgM could be demonstrated. The detectable response to STAg consisted entirely of human antibodies of the IgG isotype (IgG1), indicative of a memory type response. These results mimicked exactly the antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectious agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and secondary responses of the human donors. PMID- 7774645 TI - HIV-1 glycoprotein gp120 disrupts CD4-p56lck/CD3-T cell receptor interactions and inhibits CD3 signaling. AB - Using the CD4+ human T cell clone P28, we demonstrated that the HIV-1 glycoprotein gp120 inhibited CD3-induced inositol trisphosphate production, calcium influx and T cell proliferation. Additionally, gp120 was shown to dissociate the tyrosine kinase p56lck from CD4 in CEM cells, with a concommittant inhibition of CD4-linked kinase activity. We have addressed the question whether disruption of CD4/p56lck or CD4/CD3-T cell receptor interactions, or both, could account for the inhibitory effect of gp120 in P28 cells. By comparing the effects of various anti-CD4 monoclonal antibodies (mAb) with those of gp120, we show that gp120 and IOT4a modulate CD4 expression, and decrease CD4-associated p56lck and CD4-linked kinase activity at the plasma membrane. In contrast, OKT4A and OKT4 anti-CD4 mAb have no inhibitory effect. Interestingly, gp120 also inhibits CD3 induced Lck activation and cellular tyrosine phosphorylation, particularly of phosphoinositide-specific phospholipase C-gamma-1. Kinetic experiments reveal that the inhibitory effect of gp120 on CD3-induced tyrosine phosphorylation appears as early as 30 min, but culminate when CD4-p56lck complexes disappear from the cell surface after 4 h. These results suggest that a negative signal is triggered by gp120 that results, after a few hours, in down-modulation of CD4 p56lck complexes and the impairment of CD3 signaling. Supporting this hypothesis, gp120 inhibits CD3-linked kinase activity as shown by the inhibition of the phosphorylation of CD3 chains, leading to the inhibition of subsequent signal transduction. PMID- 7774647 TI - Characterization of the human interleukin-5 gene promoter: involvement of octamer binding sites in the gene promoter activity. AB - To investigate the human interleukin (IL)-5 gene promoter, we have constructed a plasmid with the firefly luciferase reporter gene linked to human IL-5 5' flanking sequence (nucleotides -507 to +44). We have used this plasmid to transfect the mouse EL4 T cell line, which can, under certain conditions, produce IL-5 transcripts. Phorbol 12-myristate 13-acetate, A23187 and N6, 2'-O-dibutyryl adenosine 3':5'-cyclic monophosphate co-stimulation of EL4 cells transfected with the human IL-5/luciferase reporter gene construct resulted in maximal induction of the luciferase gene. Deletion analysis of the IL-5 promoter revealed the presence of negative regulatory elements between nucleotides -404 and -312 and two regions, located between nucleotides -312 and -227 and between nucleotides 80 and -35, that are involved in the positive regulation of the IL-5 promoter. Using electrophoretic mobility shift assays, we show that the positive element located between nucleotides -312 and -227 involves the binding of factors antigenically related to Oct1, Oct2A and Oct2B, to a perfect octamer motif located at position -244/-237. Introduction of three point mutations in the octamer motif of the IL-5/luciferase reporter gene plasmid, which results in the loss of competition for the factors binding to the IL-5 promoter sequence, reduced the production of luciferase from stimulated, transfected EL4 cells, by 90%. Octamer factors can also bind within the second positive regulatory region. PMID- 7774648 TI - Impaired survival of T cell receptor V gamma 3+ cells in interleukin-4 transgenic mice. AB - The mouse epidermis contains a network of Thy-1+ dendritic T cells. Most of these cells express a homogeneous T cell receptor (TCR) configuration (V gamma 3/V delta 1) with only negligible junctional diversity. Because fetal thymocytes are precursors of these dendritic epidermal T cells (DETC) and the addition of interleukin (IL)-4 to fetal thymic organ cultures causes an early arrest in thymopoiesis, we examined DETC development in transgenic (tg) mice expressing IL 4 under the control of major histocompatibility complex class I regulatory sequences. Immunohistologic examination of epidermal sheets and polymerase chain reaction analysis of total skin RNA from IL-4 tg mice failed to reveal TCR V gamma 3+ DETC and V gamma 3 mRNA, respectively. In contrast, the sizes of TCR gamma delta subpopulations in lymphoid organs were unchanged in these mice. Although the numbers and staining intensities of TCR V gamma 3+ thymocytes in early fetal (days 14-17) IL-4 tg mice were similar to those of littermate controls, we observed a preferential death of these cells in thymic organ cultures from IL-4 tg mice. We observed further that epidermal sheets prepared from 9-day-old mice whose mothers had been treated with an IL-4-neutralizing antibody from day 12 to day 18 of pregnancy contained DETC numbers similar to those of controls. However, upon termination of the anti-IL-4 treatment, DETC ceased to expand. We conclude that IL-4 impairs the survival of TCR V gamma 3+ cells. PMID- 7774649 TI - Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes. AB - Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until now no method for the subcellular detection of iscom in situ was available. In the present study, a novel, fast and simple method for the detection of iscoms in situ is demonstrated. By making use of the lipophilic fluorescent carbocyanine dyes, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), rabies virus antigen and iscom prepared with this antigen were visualized with fluorescence microscopy. The labeled antigen and iscoms were observed in macrophages of spleen and liver of mice within 1-2 h after intravenous administration. When administered intramuscularly or in the footpad, uptake in macrophages of draining lymph nodes could be demonstrated. In the spleen, labeled inactivated virus antigen localized preferentially in the marginal zone macrophages and to a lesser extent in the red pulp macrophages. In contrast, antigen presented in iscom was taken up mainly by the marginal metallophilic macrophages and to a much lesser extend by marginal zone macrophages or follicular-dendritic and -B cells. This method enables the detection of iscom and membrane viruses and allows the analysis of their relation to antigen-presenting cells in situ. Here, we demonstrate that iscom containing rabies virus antigen are taken up by a subset of macrophages in the spleen distinct from those that take up inactivated rabies virus antigen not presented in iscom, thereby possibly explaining the observed difference in immunogenicity of these antigen preparations. Furthermore, we show a lower efficiency on the induction of humoral and cellular responses after intravenous immunization for both types of antigen when compared with subcutaneous immunization. PMID- 7774650 TI - Developmentally regulated expression of P-glycoprotein (multidrug resistance) activity in mouse thymocytes. AB - P-glycoprotein (P-gly) is the transmembrane efflux pump responsible for multidrug resistance in tumor cells. The activity of P-gly in mature peripheral lymphocytes is lineage specific, with CD8+ T cells and natural killer (NK) cells expressing high levels as compared to CD4+ T cells and B cells. We have now investigated P gly activity in immature and mature subsets of mouse thymocytes. Our data indicate that P-gly activity is undetectable in immature CD4-8- and CD4+8+ thymocyte subsets. Among mature thymocytes, P-gly activity is absent in the CD4+ subset but present in the more mature (HSAlow) fraction of CD8+ cells. Furthermore, while thymic CD4-8- T cell receptor (TCR) gamma delta cells have little P-gly activity, a minor subset of CD4-8- or CD4+ TCR alpha beta + thymocytes bearing the NK1.1 surface marker expresses high levels of P-gly activity. Collectively, our results indicate that P-gly activity arises late during thymus development and is expressed in a lineage-specific fashion. PMID- 7774651 TI - A 17-kDa CD4-binding glycoprotein present in human seminal plasma and in breast tumor cells. AB - We previously isolated gp17, a human seminal plasma glycoprotein, which specifically interacts with the D1-D2 region of CD4, a T cell surface molecule involved in antigen recognition mediated by helper T cells also acting as a receptor for the human immunodeficiency virus. In this study we report that monoclonal antibodies (mAb) reacting with gp17 are able to inhibit the binding of gp17 to immobilized soluble CD4. An immunohistochemical analysis shows that gp17 is also expressed in mammary tumor cells upon hormone treatment and in biopsies from breast cancer patients. A structural characterization of gp17, including amino acid sequencing, indicates that the protein has an extensive structural similarity with a glycoprotein designated as seminal actin-binding protein (SABP), also secreted by male sexual glands. SABP is in turn identical to gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP), a factor known as a highly specific and sensitive marker of primary and metastatic apocrine breast cancer. To establish further the correspondence of gp17 and GCDFP-15/PIP/SABP, the latter was expressed in bacteria from a cloned cDNA and purified by affinity chromatography to either anti-gp17 mAb-Sepharose or CD4-Sepharose. The purified recombinant protein is shown to inhibit the binding of labeled, pure g17 to immobilized soluble CD4. The finding that breast cancer cells express a protein able to interact with the CD4 domains involved in the recognition of class II major histocompatibility antigens suggests a possible mechanism by which a tumor may affect the activity of tumor-infiltrated CD4+ T cells. PMID- 7774652 TI - No role of interleukin-4 in CD23/IgE-mediated enhancement of the murine antibody response in vivo. AB - Antigen-specific IgE up-regulates the specific IgM, IgG1, IgG2a and IgE response in vivo when given to mice together with antigen. The enhancement is mediated by the low-affinity receptor for IgE, Fc epsilon RII or CD23, as demonstrated both in CD23-deficient mice and by blocking CD23 with anti-CD23 monoclonal antibodies. A possible mechanism behind the regulatory effects of CD23 is that the IgE/CD23/antigen complex is endocytosed by B cells, leading to increased antigen processing and presentation on major histocompatibility complex (MHC) class II molecules to T helper cells. In the present study we have found that the expression of CD23 is reduced fivefold on splenic B cells in mice genetically deficient for IL-4. When IL-4-deficient mice and normal littermates were immunized with 2,4,6-trinitrophenyl (TNP)-specific IgE followed by bovine serum albumin (BSA)-TNP or with BSA-TNP alone, the BSA-specific IgG1 and IgG2a responses were equally well augmented by IgE in all mice. In addition, a low but significant IgE response was seen even in the IL-4-deficient mice. Thus, enhancement of the antibody response through IgE and CD23 occur in the absence of IL-4 and is not dependent on CD23 up-regulation. PMID- 7774653 TI - CD38 ligation induces discrete cytokine mRNA expression in human cultured lymphocytes. AB - Human CD38 is a surface glycoprotein expressed by different immuno-competent cells such as immature and activated lymphocytes, plasma cells and natural killer cells. It has recently been reported that the CD38 molecule exerts adenosine diphosphate ribosyl cyclase activity and is associated with distinct transmembrane signaling molecules. This study reports that ligation of CD38 by specific monoclonal antibodies (mAb) induces multiple cytokine mRNA expression in cultured peripheral blood mononuclear cells (PBMC). The mRNA for tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-12 were always detected, whereas interferon gamma and IL-10 mRNA expression were seen in most, but not all PBMC cultures. Low levels of IL-2, IL-4 and IL-5 mRNA were also found. The key observation of this work is that CD38 ligation in PBMC induces a large spectrum of cytokines, many of which overlap with those induced via CD3 activation. The main differences between CD38 and CD3 activation are the low to undetectable levels of IL-2 mRNA, and the sustained IL-1 beta and IL-6 mRNA accumulation found in PBMC cultures following treatment with anti-CD38 mAb. Furthermore, PBMC proliferation was not found to be a prerequisite for CD38-mediated cytokine induction. Together, these results suggest that human CD38 activates a signaling pathway which leads to the induction of a discrete array of cytokines, and that this pathway only partially overlaps with that controlled by T cell receptor CD3. PMID- 7774654 TI - Covalent linkage of C3 to properdin during complement activation. AB - Activation of the alternative complement pathway of serum produces complexes of properdin (P) and C3 as measured in a double antibody enzyme-linked immunosorbent assay. When purified from serum, these complexes decrease factor B hemolytic activity in serum and do not restore the alternative pathway hemolytic activity of serum deficient in P. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of activated serum containing biotinylated P, followed by blotting to nitrocellulose and development with streptavidin-alkaline phosphatase revealed a band at 53 kDa for monomeric P and an additional band at 160 kDa. P samples eluted from zymosan and purified from activated serum revealed a band at 116 kDa for C3 alpha and 74 kDa for C3 beta, and an additional band at 160 kDa when analyzed by SDS-PAGE, Western blotting and development with antibody to C3. The appearance of a 160 kDa band containing P and C3 indicates that these proteins are contained in a complex formed during activation of the alternative pathway. Activation of a purified reagent mixture containing factors B, D, and H, and 125I labeled P or 125I-labeled C3, followed by SDS-PAGE and autoradiography confirmed the presence of a 160-kDa band which disappeared following hydroxylamine treatment of the sample. These data are consistent with a covalent linkage of C3 to P via the C3 alpha chain, producing the 160-kDa complex. PMID- 7774655 TI - Stimulation of rat striatal tyrosine hydroxylase activity following intranigral administration of sigma receptor ligands. AB - The effects of sigma ligands on turning behavior and striatal tyrosine hydroxylase activity were determined following microinjection of two chemically dissimilar sigma ligands into the rat substantia nigra. Striatal tyrosine hydroxylase activity was monitored by measuring the amount of 3,4 dihydroxyphenylalanine (DOPA) formed following inhibition of DOPA decarboxylase activity with m-hydroxybenzylhydrazine (NSD-1015). The sigma ligands, 1,3-di-o tolylguanidine (DTG) and (-)-deoxy-N-benzylnormetazocine, produced a significant increase both in contralateral turning and in tyrosine hydroxylase activity. The DTG-induced increase in tyrosine hydroxylase activity was not antagonized by intranigral injection of the NMDA receptor antagonist, 3-(2-carboxypiperazine-4 yl)-propyl-1-phosphonic acid (CPP). CPP alone produced significant contralateral turning that was not accompanied by an increase in striatal tyrosine hydroxylase activity, indicating that turning per se is not sufficient to activate striatal tyrosine hydroxylase. The DTG-induced increase in tyrosine hydroxylase activity was antagonized by general anesthetics such as halothane and chloral hydrate. These results indicate that occupancy of sigma receptors in the substantia nigra is associated with an activation of dopamine formation in dopaminergic terminals in the striatum and support the concept that sigma activity in the substantia nigra produces an activation of dopamine-mediated responses in the striatum. PMID- 7774656 TI - An antisense oligodeoxynucleotide to mu-opioid receptors inhibits mu-opioid receptor agonist-induced analgesia in rats. AB - We examined effects of an antisense oligodeoxynucleotide against the mu-opioid receptor on mu-opioid receptor agonist-induced antinociception in the cold water (-3 degrees C) tail-flick test in rats. Rats were injected intracerebroventricularly (i.c.v.) with an antisense, sense or missense oligodeoxynucleotide or artificial cerebrospinal fluid on days 1, 3 and 5. On day 6, antinociceptive effects of opioid agonists were tested. Compared to the artificial cerebrospinal fluid treatment, the cumulative dose-effect curve for subcutaneous (s.c.) morphine was shifted to the right by the antisense oligodeoxynucleotide, but not by the missense oligodeoxynucleotide or the sense oligodeoxynucleotide treatment. Antisense oligodeoxynucleotide treatment reduced the analgesic effect of the mu-opioid receptor agonist PL017 ([N-MePhe3,D Pro4]morphiceptin), but not the delta-opioid receptor agonist BW373U86 ((+/-)-4 ((a-R*)-a-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N diethyl-benzamide) or the kappa-opioid receptor agonist spiradoline ((+/-) (5a,7a,8b)-3,4-dichloro-N-methyl-N-[7-(1- pyrrolidinyl)-1-(oxaspiro-[4,5]dec-8 yl]benzeneacetamide monohydrochloride). The drugs were given by i.c.v. injection. These findings indicate that i.c.v. administration of a mu antisense oligodeoxynucleotide specifically blocks mu-, but not delta- or kappa-opioid receptor-mediated analgesia in the rat cold water tail-flick test. PMID- 7774657 TI - Antinociceptive effect of dihydroetorphine in diabetic mice. AB - The antinociceptive potency of dihydroetorphine in diabetic mice was examined. Subcutaneous administration of dihydroetorphine produced a dose-dependent antinociception in both non-diabetic and diabetic mice. The antinociceptive potency of s.c. dihydroetorphine was less in diabetic mice than in non-diabetic mice. The antinociception induced by i.c.v. dihydroetorphine (0.02 microgram) was also significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effects of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in non-diabetic mice, but not in diabetic mice, was also significantly antagonized by naloxonazine, a selective mu 1-opioid receptor antagonist. The time course and the potency of the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in diabetic mice were similar to those in naloxonazine treated non-diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice. These results suggest that dihydroetorphine produces an antinociceptive effect through the activation of both mu 1- and mu 2-opioid receptors in mice. Furthermore, the reduction in dihydroetorphine-induced antinociception in diabetic mice, as compared with non diabetic mice, may be due to the hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception in diabetic mice. PMID- 7774658 TI - Effect of combination of a tissue-type plasminogen activator and an endothelin receptor antagonist, FR139317, in the rat cerebral infarction model. AB - We were interested to investigate if a combination of a modified tissue-type plasminogen activator, SUN9216, which is constructed by modifying a single amino acid (Asn117-Gln117) to yield a tissue-type plasminogen activator lacking finger and growth factor domains with a long half-life in blood, and an endothelin receptor antagonist, FR139317, (R)2-[(R)-2-[(S)-2[[1-(hexahydro-1H azepinyl)]carbonyl]amino-4- methyl-pentanoyl]amino-3-[3-(1-methyl-1H indolyl)]propionyl)amino-3- (2-pyridyl)propionic acid, has greater thrombolytic efficacy than a thrombolytic agent alone in reducing the size of cerebral infarction. The thrombotic occlusion of the rat middle cerebral artery was induced by a photochemical reaction between rose bengal and green light, which causes endothelial injury followed by platelet adhesion and formation of a platelet-rich thrombus. SUN9216 (1 mg/kg) was injected intravenously 30 min after the middle cerebral artery occlusion and the time for reopening of the middle cerebral artery by SUN9216 was monitored for a 60-min period under an operating microscope. In the rats in which thrombolysis was achieved with SUN9216, the size of the cerebral infarction was significantly (P < 0.05) reduced as compared with that in the rats treated with saline and was comparable to the reduction produced by the combination doses. It is concluded that, under the present experimental conditions, endothelin may not be involved in the impaired local cerebral blood flow after thrombolysis. PMID- 7774659 TI - The effects of adenosine A3 receptor stimulation on seizures in mice. AB - We have previously shown that acute preischemic adenosine A3 receptor stimulation results in an increased postischemic damage, while chronic stimulation of this receptor diminishes it. Since several pathophysiological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenosine A3 receptor selective agonist IB-MECA (N6-(3 iodobenzyl) adenosine-5'-N-methylcarboxamide) prior to seizures induced by N methyl-D-aspartate (NMDA), pentamethylenetetrazole, or electric shock. At 100 micrograms/kg, acutely injected IB-MECA was protective in chemically but not electrically induced seizures. In chronic administration of IB-MECA, significant protection against chemically induced seizures was obtained in all studied measures, i.e., seizure latency, neurological impairment, and survival. Although threshold voltage was unchanged in electrically induced seizures, a chronic regimen of IB-MECA significantly reduced postepileptic mortality. Since the combination of an arteriole-constricting compound 48/80 and hypotension-inducing clonidine injected prior to NMDA results in a significant protection against seizures, and since acute stimulation of adenosine A3 receptor causes both arteriolar constriction and severe hypotension, there is a possibility that the protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB-MECA is related to the effect of the drug on blood flow, neuronal mechanisms, or both. PMID- 7774660 TI - Interleukin-1 receptor antagonist displays intrinsic agonist activity on rat gastric fundus motility in vitro. AB - It has been shown previously that both forms of interleukin-1, 1 alpha and 1 beta, produce dose-dependent relaxation of the rat gastric fundus in vitro, accompanied by an increased production and release of eicosanoids. This effect appears to be mediated, at least in part, by leukotrienes, since the inhibition of 5-lipoxygenase by specific drugs counteracts interleukin-1-induced gastric relaxation. In the present study, we attempted to antagonize interleukin-1 induced inhibition of gastric fundus motility with a interleukin-1 receptor antagonist. Surprisingly, the interleukin-1 receptor antagonist itself possessed interleukin-1-like agonist activity, since: (a) it produced rapid, dose-dependent relaxation of the rat gastric fundus, with an estimated EC50 of 70 pg/ml and a maximal effect at 10 ng/ml; (b) interleukin-1 receptor antagonist-induced relaxation was dose dependently inhibited by N-(3-phenoxycinnamyl)acetohydroxamic acid (BW A4c), a specific inhibitor of 5-lipoxygenase; (c) in the first 5 min after its addition to the bath solution, interleukin-1 receptor antagonist produced a significant increase in prostaglandin E2 release from the gastric strips. This evidence suggests that, shortly after receptor occupancy, in this experimental model interleukin-1 and interleukin-1 receptor antagonist share the same pattern of mechanical and biochemical activities. PMID- 7774661 TI - Developmental changes in response to endothelins and receptor subtypes of isolated rat duodenum. AB - The response of isolated duodenum to endothelin-1, -3 and IRL 1620 (Suc [Glu9,Ala11,15]endothelin-1 (8-21)), a selective endothelin ETB receptor agonist, was studied in both neonatal (1-week-old) and adult rats by recording mechanical activity isotonically. Endothelin-1, -3 and IRL 1620 (1-100 nM) elicited sustained contraction of neonatal duodenum, in a concentration-dependent manner, with a potency order of endothelin-1 = endothelin-3 > IRL 1620. The response to endothelin-1 and -3 (10-1000 nM) of adult duodenum was biphasic, i.e., transient relaxation followed by contraction, with a potency order of endothelin-1 > endothelin-3. The contractile response to endothelin-1 of adult but not neonatal duodenum was significantly antagonized by pretreatment with FR139317 (1 microM), an endothelin ETA receptor antagonist. An endothelin ETB receptor antagonist, RES 701-1 (3 microM), weakly antagonized the IRL 1620-induced contraction of neonatal duodenum. However, RES-701-1 (10 microM) did not affect the response to endothelin-1 of either adult or neonatal duodenum. These results indicate that the duodenal response to endothelins changes from a sustained contraction in neonates to a biphasic response in adults. The contractile response to endothelins of neonatal duodenum is suggested to be mediated through endothelin ETB receptors or possibly RES-701-1-resistant ETB receptor subtypes and contraction of adult duodenum through endothelin ETA receptors. The mechanism of the endothelin-induced response of duodenum was also studied. PMID- 7774662 TI - Depletion of cortical cholecystokinin levels after excitotoxin injection into the nucleus basalis: sensitivity to MK-801. AB - The release of cholecystokinin (CCK) in vitro has been shown to be influenced by NMDA receptors. In this study we have investigated whether excitotoxin-induced seizure activity affects the release and tissue content of CCK. Excitotoxin injection caused a significant decrease in CCK in ipsilateral frontal, parietal and temporal cortex by (30-54%) at 8 h compared to contralateral cortex and sham operated controls and the effect was reversed by 24 h. No change was detected in occipital cortex, hippocampus and nucleus accumbens. The effect in frontal and temporal cortex was maximal at 8 h and could be completely prevented by treatment with MK-801(3 mg/kg i.p.). Anaesthesia (pentobarbital) alone or in combination with MK-801 did not affect peptide levels at 8 h. CCK mRNA levels were also studied quantitatively by slot-blot analysis but were unaffected at 6, 8 and 24 h after excitotoxin injection. The decrease in CCK tissue levels indicated that seizure activity stimulated CCK release which was confirmed in ex vivo experiments where K(+)-evoked (34 mM) CCK release was significantly enhanced in ipsilateral cerebral cortex at 6 h compared to contralateral cortex. PMID- 7774663 TI - The membranes of cultured rat brain astrocytes contain endothelin-converting enzyme activity. AB - Both endothelins and their big-endothelin precursors were found capable of inducing the release of arachidonic acid from purified cultures of rat astrocytes. Their order of potency was as follows: big-endothelin-3 < big endothelin-1 < endothelin-1 = endothelin-3. Mature endothelins induced the release of arachidonic acid in a rapid fashion. In contrast, much longer incubation times were required for big-endothelins to exert an effect, suggesting that their activity was dependent on their conversion. When big-endothelin-1 was added to the incubation medium of intact live astrocytes, it was converted into mature endothelin-1 in a time-dependent manner and the conversion was inhibited by phosphoramidon. This suggests that astrocytic endothelin-converting enzyme is (at least in part) an external membrane-bound metalloprotease. Some conversion of big-endothelin-3 into endothelin-3 also occurred. However, it was less efficient than the conversion of big-endothelin-1, which is compatible with the lower bioactivity of big-endothelin-3 vs. that of big-endothelin-1 in astrocytes. PMID- 7774664 TI - Effects of the dopamine autoreceptor antagonist (-)-DS121 on the discriminative stimulus properties of d-amphetamine and cocaine. AB - (-)-DS121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine) is a recently synthesised phenylpiperidine derivative suggested to be a dopamine receptor antagonist acting preferentially at dopamine autoreceptors. The drug exerts 'agonist-like' behavioural effects by enhancing dopamine release, but also shares properties in common with neuroleptics. The ability of (-)-DS121 to both generalise to and antagonise the stimulus effects of psychostimulants was determined in rats trained to discriminate d-amphetamine (0.5 mg/kg) or cocaine (5.0 mg/kg) from saline in a two-lever, food-reinforced, drug discrimination task. (-)-DS121 (3.5-14.0 mg/kg) produced small, but significant, increases in drug lever-appropriate responding in both d-amphetamine and cocaine-trained rats. However, there was no indication of a dose-dependent effect in either case. On the other hand, (-)-DS121 dose-dependently reduced response rate. Caffeine produced a higher level of drug lever-appropriate responding than (-)-DS121 in d amphetamine-trained rats. (-)-DS121 (7.0-14.0 mg/kg) also weakly antagonised the cueing properties of both d-amphetamine and cocaine. A marked response disruption with the drug combination precluded testing of higher doses of (-)-DS121. A combination of subthreshold doses of (-)-DS121 (3.5 mg/kg) and d-amphetamine (0.0625 mg/kg) produced a significant degree of drug lever-appropriate responding, suggesting a synergistic interaction between these drugs. However, such an interaction was not noted with a higher dose of (-)-DS121, or when this drug was administered with a low dose of cocaine (0.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774665 TI - Phosphodiesterase inhibitors reduce bronchial hyperreactivity and airway inflammation in unrestrained guinea pigs. AB - A new guinea pig model of allergic asthma was used to investigate the effects of low doses of the phosphodiesterase inhibitors, rolipram (phosphodiesterase IV selective), ORG 20241 (N-hydroxy-4-(3,4-dimethoxyphenyl)-thiazole-2 carboximidamide; dual phosphodiesterase III/IV inhibitor with some selectivity for the phosphodiesterase IV isoenzyme), and of theophylline (non-selective) on allergen-induced early and late phase asthmatic reactions, bronchial hyperreactivity to histamine inhalation, and airway inflammation. Theophylline (25 mg/kg i.p.) and ORG 20241 (5 mg/kg i.p.) did not affect histamine-induced bronchoconstriction, whereas rolipram (75 micrograms/kg i.p.) only slightly reduced the response to histamine at 7 h after administration. However, bronchial hyperreactivity after the early and after the late reaction was significantly reduced by theophylline, rolipram and ORG 20241, while bronchoalveolar lavage studies revealed a selective inhibition of airway inflammation by the phosphodiesterase inhibitors. Theophylline significantly reduced the number of eosinophils, neutrophils and macrophages; rolipram reduced the number of neutrophils and lymphocytes, and ORG 20241, the number of eosinophils and macrophages. None of the compounds at the dosage indicated reduced the early and late reaction when administered i.p. 1 h before allergen exposure to defined dual responding animals. These results indicate that non-bronchodilator doses of these phosphodiesterase inhibitors markedly reduce the allergen-induced development of bronchial hyperreactivity as well as airway inflammation, presumably by selectively inhibiting cellular migration. The results suggest that an orchestrated series of cellular interactions is involved in the development of bronchial hyperreactivity. It is concluded that phosphodiesterase inhibitors may be very useful in the treatment of bronchial asthma. PMID- 7774666 TI - Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine. AB - The specific opioid receptor antagonist naloxone modifies the effects of amphetamine in a wide variety of behavioral paradigms. Naloxone also attenuates the amphetamine-induced increase in extracellular dopamine in the brain of rats. Therefore, these experiments were designed to replicate the neurochemical and behavioral interactions between naloxone and amphetamine, and to extend these observations to interactions between naloxone and cocaine. Microdialysis was performed on adult male rats of Sprague-Dawley descent. Rats were pretreated with a subcutaneous injection of 5.0 mg/kg naloxone or vehicle, which was followed 30 min later by cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, 6.4 mg/kg) or intraperitoneal cocaine (0, 3, 10, 30, 56 mg/kg) at 30 min intervals. The microdialysis probes were perfused at a flow rate of 0.6 microliter/min with artificial cerebrospinal fluid. Dialysate samples were collected every 10 min from either the nucleus accumbens or striatum and analyzed for dopamine content by high-performance liquid chromatography (HPLC). Locomotor activity (photobeam breaks) was monitored simultaneously with the collection of dialysate samples. Amphetamine and cocaine dose-dependently increased extracellular dopamine in both the nucleus accumbens and striatum. Naloxone pretreatment significantly reduced the amphetamine-induced increase in extracellular dopamine in both brain regions and also attenuated the increase in locomotor activity elicited by amphetamine. Naloxone pretreatment had no effect, however, on the cocaine-induced increase in extracellular dopamine or locomotor activity. These findings suggest that endogenous opioid systems play a role in mediating the neurochemical and behavioral effects of amphetamine, but not those of cocaine. PMID- 7774668 TI - Homologous and heterologous regulation of receptor-stimulated phosphoinositide hydrolysis. AB - Signal transduction at a diverse range of pharmacologically distinct receptors is effected by the enhanced turnover of inositol phospholipids, with the attendant formation of inositol 1,4,5-trisphosphate and diacylglycerol. Although considerable progress has been made in recent years towards the identification and characterization of the individual components of this pathway, much less is known of mechanisms that may underlie its regulation. In this review, evidence is presented for the potential regulation of inositol lipid turnover at the level of receptor, phosphoinositide-specific phospholipase C and substrate availability in response to either homologous or heterologous stimuli. Available data indicate that the extent of receptor-stimulated inositol lipid hydrolysis is regulated by multiple mechanisms that operate at different levels of the signal transduction pathway. PMID- 7774667 TI - Evidence for two different imidazoline sites on pancreatic B cells and vascular bed in rat. AB - The relative potencies of imidazoline compounds to induce insulin secretion and vascular resistance were compared in the isolated perfused rat pancreas. On insulin secretion, only the two imidazolines, antazoline and efaroxan, induced a concentration-dependent response, antazoline being 10 times more potent than efaroxan. In contrast, idazoxan, a blocker of imidazoline I1 sites, at concentrations up to 30 microM, antagonized the insulin response to 10 microM efaroxan (IC50 approximately equal to 14 +/- 2 microM) without affecting that to 3 microM tolbutamide. On pancreatic vessels, not only antazoline and efaroxan but also idazoxan induced a concentration-dependent vasoconstriction; the rank order of agonist potency was antazoline > efaroxan > idazoxan. In addition, cimetidine, an imidazole known to bind imidazoline I1 sites, ineffective per se, partially reversed the insulin stimulatory effect of efaroxan without affecting its vasoconstrictor effect. This study demonstrates that the insulin secretory and vasoconstrictor actions of imidazolines involve different imidazoline sites in rat pancreas. The results provide evidence for an I1 type mediating insulin secretion on B cells and an I2 type mediating vasoconstriction in vessels. PMID- 7774669 TI - The function of a highly-conserved arginine residue in activation of the muscarinic M1 receptor. AB - Arg123 in the rat muscarinic M1 receptor is part of the highly conserved triad Asp-Arg-Tyr found at the junction of transmembrane helix 3 with the second intracellular loop. Mutation of Arg123 to Lys, Ala, Leu, Glu and Gln had no effect on levels of receptor expression in COS-7 cells, or on affinities for the antagonist N-methylscopolamine. Acetylcholine stimulation of the Lys123 receptor evoked the same maximum phosphoinositide response as the wild type, although the potency was reduced six-fold, but mutation to other residues strongly disrupted receptor function. Mutation of Arg123 always decreased the ratio of the high affinity to the low affinity agonist binding constant, but the absolute effect on the latter varied from a 4-fold increase for the Lys123 to a small decrease for the Leu123 mutation. These results suggest that a positive charge at position 123 is central to the activation of G-proteins by the muscarinic M1 receptor. PMID- 7774670 TI - Pharmacological properties of two recombinant splice variants of the PACAP type I receptor, transfected and stably expressed in CHO cells. AB - Two splice variants of the pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PACAP receptor and PACAP/HOP receptor isoform) were stably expressed in Chinese hamster ovary (CHO) cells that did not express constitutively receptors for this family of peptides. The PACAP/HOP receptor protein had a 28 amino acid extension in the C-terminal part of the third intracellular loop. The two cell lines studied, CHO 2-10 (PACAP receptor) and CHO 4-12 (PACAP/HOP receptor) expressed a receptor density of 4.6 +/- 0.3 and 2.6 +/- 0.2 pmol/mg protein, respectively, with corresponding Kd values of 14.2 +/- 2.0 and 8.2 +/- 1.0 nM for [Ac-His1]PACAP-27 used as a tracer. Tracer binding was slightly decreased by GTP in both clones. The Kd values of PACAP-27, PACAP-38, vasoactive intestinal peptide (VIP), PACAP-27 fragments and analogues evaluated by binding competition curves, were higher in CHO 2-10 than in CHO 4-12, whereas the Kd for PACAP-38 fragments did not differ. The receptors were coupled to adenylate cyclase and the EC50 values were lower than the Kd values in both cell lines, suggesting an amplification process due to the existence of spare receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774671 TI - Polyclonal antibodies against human melanocortin MC1 receptor: preliminary immunohistochemical localisation of melanocortin MC1 receptor to malignant melanoma cells. AB - Peptides of 11 and 15 residue lengths were synthesised according to the sequence of the N-terminal region of the human MC1 melanocyte stimulating hormone receptor. The peptides were conjugated to thyroglobulin and used for preparation of antisera in the rabbit. Each of the conjugates raised antisera which showed high titre and specificity for its respective peptide antigen when evaluated in an ELISA test. Both types of antisera immunostained MC1 receptor expressing COS-7 cells. By contrast, the sera did not stain control COS-7 cells not expressing the MC1 receptor. Moreover, preimmune sera or antiserum preadsorbed with its respective peptide did not stain the MC1 receptor expressing cells. The antisera were used to immunostain sections of normal human skin, as well as samples of cutaneous malignant melanoma tumours obtained from a patient. The cells of the melanoma tumours were very strongly immunostained with the MC1 receptor antisera. By contrast, melanocytes which were present in the normal skin could not be visualised with our antisera. PMID- 7774673 TI - Evidence that beta-endorphin is an agonist at bovine pineal delta-opioid receptors. AB - Since beta-endorphin is the putative endogenous ligand for epsilon-opioid receptors, the previous demonstration of saturable, high affinity beta-endorphin binding sites on bovine pineal membranes suggests the possible presence of epsilon-opioid receptors. To determine the identity of pineal beta-endorphin binding sites, the inhibition of [125I]beta-endorphin binding by ligands with varying affinities for epsilon-, mu-, delta- or kappa-opioid receptors was investigated. A high positive correlation was observed between the Ki values for these drugs to inhibit [125I]beta-endorphin binding to pineal membranes and for these drugs to bind to delta-opioid receptors but not to mu-, kappa- or epsilon opioid receptors, demonstrating that in the pineal beta-endorphin binds to delta opioid receptors. Both NaCl and a GTP analogue were potent inhibitors of [125I]beta-endorphin binding, providing evidence that beta-endorphin is an agonist at pineal delta-opioid receptors. These results suggest that endogenous bovine beta-endorphin may modulate pineal function. PMID- 7774672 TI - Structure-activity relationship of bromoeudistomin D, a powerful Ca2+ releaser in skeletal muscle sarcoplasmic reticulum. AB - Bromoeudistomin D and 9-methyl-7-bromoeudistomin D which have a beta-carboline skeleton are powerful Ca2+ releasers from skeletal muscle sarcoplasmic reticulum exhibiting caffeine-like properties. We examined the effects of bromoeudistomin D analogues on Ca(2+)-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum. Among bromoeudistomin D analogues, the Ca(2+)-releasing activities of carboline derivatives were higher than those of carbazole derivatives, suggesting that a carboline skeleton is significantly important for the manifestation of Ca(2+)-releasing activity and Ca2+ sensitivity of Ca(2+)-induced Ca2+ release. On the contrary, the analogues which have a carbazole skeleton and bromine at C-6 inhibit both Ca(2+)- and caffeine-induced Ca2+ release. 9-Methyl-substitution of the analogue elevated its Ca(2+)-releasing activity. Moreover, there is a close correlation between the enhancement of [3H]ryanodine binding to sarcoplasmic reticulum by the analogues and the activation of Ca2+ release by them. Bromoudistomin D analogues may provide valuable information about the structure function relationship of the ryanodine receptor/Ca2+ release channels in skeletal muscle sarcoplasmic reticulum. PMID- 7774674 TI - Effect of receptor density on the receptor-effector coupling: use of cloned and stably expressed alpha 1B-adrenoceptors in CHO cells. AB - Using Chinese hamster ovary cells stably expressing alpha 1B-adrenoceptor as a model, we investigated whether the changes in receptor density may influence the receptor-effector coupling relationship. Among the transfected cells, two clones which showed similar pharmacological properties but markedly differed in receptor density (Bmax were 1600 and 110,000 sites/cell, respectively), were examined. The phenoxybenzamine inactivation method showed that the alpha 1B-adrenoceptor occupancy and transients of cytosolic Ca2+ concentration ([Ca2+]i) response relationship was markedly nonlinear but similar in the two cell lines. The dose response relationship for norepinephrine-induced [Ca2+]i response showed an increase in maximum effect with no change in agonist potency, and the increase in maximum effect was disproportionate to the difference in receptor density. The results indicate that the classical model of drug-receptor action cannot appropriately describe the coupling of alpha 1B-adrenoceptor to [Ca2+]i response in the single receptor expressing system. PMID- 7774676 TI - Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function. AB - We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1 (7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774675 TI - Characterisation of melanocortin receptor subtypes by radioligand binding analysis. AB - The DNAs encoding three melanocortin receptor subtypes (melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC5 receptor) were expressed individually in COS (CV-1 Origin, SV40) cells to characterise their ligand binding properties. The results indicated that [125I][Nle4, D-Phe7]alpha-MSH (melanocyte stimulating hormone) bound to a single saturable site with Kd values of 85.1 +/- 8.0 pmol/l (mean +/- S.E.M), 396 +/- 65 pmol/l and 5.05 +/- 1.00 nmol/l for melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC3 receptor, respectively. The melanocortin MC1 receptor and the melanocortin MC5 receptor showed a similar potency order to the melanocortic peptides examined which was markedly different from the potency order of the melanocortin MC3 receptor. The melanocortin MC1 receptor and melanocortin MC5 receptor had a relatively higher affinity for alpha-MSH than gamma-MSH and beta-MSH, whereas the melanocortin MC3 receptor had higher affinity for desacetyl-alpha-MSH, gamma-MSH and beta-MSH compared to alpha-MSH. The inclusion of the endopeptidase inhibitor phosphoramidon to prevent the breakdown of ACTH-(1-39) (adrenocorticotrophic hormone) to alpha-MSH, decreased ACTH-(1-39) binding affinity showing that ACTH (1-39) had a much lower affinity for melanocortin MC1 receptor than reported earlier. PMID- 7774677 TI - Atrial natriuretic factor stimulates migration by human neutrophils. AB - Atrial natriuretic factor causes a strong stimulation of human neutrophil migration in the concentration range of 4 x 10(-9) and 10(-7) M. The effect, which depends on the presence of extracellular Mg2+ but not on extracellular Ca2+, is composed of a chemokinetic and a chemotactic component. Cyclic GMP level of neutrophils is enhanced by atrial natriuretic factor. Two inhibitors of soluble guanylate cyclase, 6-anilino-5,8-quinolinedione (LY 83583) and methylene blue, have no effect on stimulation of migration by atrial natriuretic factor. Atrial natriuretic factor-activated migration is inhibited by pertussis toxin. Migration by electroporated neutrophils is synergistically enhanced by guanosine 5'-[gamma thio]triphosphate (GTP gamma[S]) and atrial natriuretic factor or by GTP gamma[S] and chemotactic peptide, while GTP gamma[S] and dioctanoyl glycerol give an additive effect. The results suggest that besides a modulation via cGMP a part of the effect of atrial natriuretic factor on migration is regulated via the ANF receptor-subtype that does not activate guanylate cyclase. PMID- 7774679 TI - Prolonged incubation with neuropeptide Y upregulates beta-adrenoceptors yet does not cause supersensitivity of beta-adrenoceptor signaling. AB - In neonatal rat ventricular myocytes prolonged incubation with 1 microM neuropeptide Y (2 h-48 h) increased beta-adrenoceptor density 16-24% (n = 4--8, all p < 0.05), an effect prevented by pertussis toxin pretreatment. Prolonged incubation with neuropeptide Y had no effect on adenylycylclase activity stimulated by 5'-guanylylimidodiphosphate or (-)-isoprenaline, probably because of a neuropeptide Y-induced decrease in affinity of the beta-adrenoceptor for agonist. Thus, chronic incubation with an inhibitory agonist does not inevitably lead to supersensitivity of the adenylylcyclase pathway. PMID- 7774678 TI - Daphnoretin-induced respiratory burst in rat neutrophils is, probably, mainly through protein kinase C activation. AB - Daphnoretin, a dicoumarin isolated from Wikstroemia indica C.A. Mey. (Thymelaceae), induced superoxide anion (O2-) formation in rat neutrophils in a concentration-dependent manner. Addition of staurosporine reduced daphnoretin induced respiratory burst. Removal of extracellular free Ca2+ by EGTA did not affect the respiratory burst of neutrophils in response to daphnoretin. Prior exposure of neutrophils to phorbol 12-myristate 13-acetate (PMA) or daphnoretin reduced the O2- formation caused by a subsequent challenge with PMA and daphnoretin, but potentiated the response caused by a subsequent addition of formyl-Met-Leu-Phe (fMLP). Like PMA, daphnoretin did not increase the [Ca2+]i during cell activation. In neutrophil suspension, daphnoretin increased the membrane associated protein kinase C activity. In the presence of Ca2+ and phosphatidyl-serine, daphnoretin also activated protein kinase C isolated from cytosolic fraction of resting neutrophils. Staurosporine inhibited the direct activation of protein kinase C caused by daphnoretin as well as by PMA. Daphnoretin reduced the [3H]Phorbol-12,13-dibutyrate ([3H]PDB) binding to the neutrophil cytosolic protein kinase C in a concentration-dependent manner with an IC50 value of 1.77 +/- 0.37 microM. These results indicate that daphnoretin, like PMA, may direct activation of protein kinase C which in turn activated NADPH oxidase and elicited respiratory burst. PMID- 7774680 TI - Inhibition of voltage-dependent Ca(2+)-current by alpha-adrenoceptor agonists in smooth muscle cells. AB - The cellular mechanisms underlying the inhibitory effects of phenylephrine on dihydropyridine-sensitive, voltage-dependent Ca2+ currents recorded from single smooth muscle cells dissociated from the rat anococcygeus muscle were examined. Phenylephrine (0.1-30 microM) produced a concentration-dependent inhibition of the Ca2+ current; the maximum response occurred at a concentration of 10 microM, which inhibited the peak inward current evoked at 0 mV by 57.7 +/- 4% (n = 8). The response to phenylephrine was reduced but not abolished in cells containing 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), and it persisted in cells dialysed internally with heparin (5 mg.ml-1). This was despite the fact that both EGTA (5 mM) and heparin were able to block the phenylephrine induced, Ca(2+)-dependent chloride current recorded in the same cells. The inhibition of the Ca2+ current produced by phenylephrine was abolished in cells containing guanosine 5'-[beta-thio]diphosphate (GDP-beta-S) but persisted in cells pre-treated with pertussis toxin. Our results suggest that the inhibition of L-type Ca2+ current seen following alpha-adrenoceptor activation occurs by a mechanism independent from the inositol trisphosphate-mediated release of Ca2+ from intracellular stores. PMID- 7774681 TI - Glucocorticoids regulate the expression of angiotensin AT1 receptors, in the human hepatoma cell line, PLC-PRF-5. AB - The effects of different steroids on the expression of angiotensin AT1 receptors by the human hepatoma cell line, PLC-PRF-5 was studied. Dexamethasone and aldosterone decreased the specific binding of [3H]angiotensin II to intact PLC PRF-5 cells by 57 +/- 4% and 54 +/- 2%, respectively, compared to control, untreated cells. EC50 values for dexamethasone, cortisol and aldosterone were 1.8 +/- 0.6, 40 +/- 6, and 310 +/- 20 nM, respectively, suggesting that these effects were mediated via a glucocorticoid receptor. Scatchard analysis revealed that dexamethasone decreased the number of angiotensin AT1 receptors expressed (50 +/- 4% relative to control) with no change in receptor affinity. Treating cells with dexamethasone in the presence of either an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist did not prevent the reduction in angiotensin AT1 receptor expression, ruling out a mechanism involving a dexamethasone induced increase in endogenous angiotensin II production. A ribonuclease protection assay established that the steady state level of angiotensin AT1 receptor mRNA in dexamethasone treated cells was reduced to 34.7 +/- 8.4% of untreated cells. The decrease in the number of angiotensin AT1 receptors expressed on the cell surface after treatment with dexamethasone therefore seems likely to reflect the decreased steady state level of the mRNA coding for this receptor. PMID- 7774682 TI - Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets. AB - The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists N-(6-aminohexyl)-5-chloro 1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca2+ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca2+. Sertraline, calmidazolium and W-7 also caused large dose dependent increases in baseline levels of intracellular Ca2+. There was a rough correlation between the ability to elevate intracellular Ca2+ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP3) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP3 and calmodulin in the effects of these drugs. PMID- 7774683 TI - Ouabain enhances nitric oxide synthesis in rat vascular smooth muscle cells induced by interleukin-1 beta. AB - Incubation of cultured rat vascular smooth muscle cells with interleukin-1 beta caused a significant increase in the production of nitrite, a stable metabolite of nitric oxide (NO), in time- and dose-dependent manners. Addition of ouabain to the culture further enhanced interleukin-1 beta-induced nitrite production. Similarly, interleukin-1 beta produced a significant increase in the cellular level of guanosine 3',5'-cyclic monophosphate, and the increase was significantly enhanced by coincubation with ouabain. The calcium ionophore ionomycin also significantly enhanced interleukin-1 beta-induced nitrite generation. These findings indicate that ouabain enhances NO synthesis in vascular smooth muscle cells induced by interleukin-1 beta, presumably through an increase in intracellular calcium ion concentrations. PMID- 7774684 TI - 5-HT1A receptor-mediated activation of high-affinity GTPase in rat hippocampal membranes. AB - GTP hydrolyzing activity was assayed by measuring the amount of 32P(i) released from 0.3 microM [gamma-32P]GTP in the membranes prepared from rat brain. 5 Hydroxytryptamine (5-HT) stimulated the high-affinity GTPase activity in hippocampus, but not in striatum, in a concentration-dependent manner with an EC50 value of 18 nM and maximal percent stimulation of 13.9%. This response was mimicked by (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin [(+/-)-8-OH-DPAT], but not by (+/-)-1-(2,5-dimethoxy-4-iodophyenyl)-2-aminopropane [(+/-)-DOI]. These results suggest that 5-HT-stimulated high-affinity GTPase activity of the GTP binding protein(s) is mediated via 5-HT1A receptor subtype in the rat hippocampus. PMID- 7774685 TI - Profiling of trans-azetidine-2,4-dicarboxylic acid at the human metabotropic glutamate receptors mGlu1b, -2, -4a and -5a. AB - We have tested the two enantiomers of trans-azetidine-2,4-dicarboxylic acid, (2S,4S)-azetidine-2,4-dicarboxylic acid ((2S,4S)-ADA) and (2R,4R)-azetidine-2,4 dicarboxylic acid ((2R,4R)-ADA) for activity at the human metabotropic glutamate receptors mGlu1b, mGlu2, mGlu4a and mGlu5a expressed in mammalian cells. In Chinese hamster ovary (CHO) cells expressing human mGlu2 receptors, 500 microM (2S,4S)-ADA inhibited forskolin-stimulated cAMP accumulation by 33 +/- 3% while 100 microM (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid induced an inhibition by 66 +/- 5%. The (2R,4R)-ADA enantiomer was inactive at human mGlu2 receptors. In CHO cells expressing human mGlu4a receptors, 10 microM L-AP4 inhibited forskolin-stimulated cAMP levels by 37 +/- 4% whereas both ADA enantiomers of trans-azetidine-2,4-dicarboxylic acid (500 microM) had no such effect. In CHO cells expressing human mGlu1b receptors and L cells expressing human mGlu5a receptors, both enantiomers, applied at 500 microM or 1 mM, were ineffective in stimulating inositolmonophosphate accumulation and did not affect quisqualate-stimulated inositolmonophosphate accumulation. We conclude that (2S,4S)-azetidine-2,4-dicarboxylic acid is a weak human mGlu2 receptor agonist and that (2R,4R)-azetidine-2,4-dicarboxylic acid is inactive at human mGlu2 receptors. Trans-azetidine-2,4-dicarboxylic acid has no significant agonistic effect on human mGlu4a receptors and neither agonistic nor antagonistic effects on human mGlu1b and mGlu5a receptors. PMID- 7774686 TI - Activation of phospholipase C by G-protein beta gamma subunits in DDT1MF-2 cells. AB - Adenosine A1 receptors directly stimulate inositol phospholipid hydrolysis and Ca2+ mobilization through a pertussis toxin sensitive mechanism in DDT1MF-2 cells. In the present study we have investigated whether G protein beta gamma subunits (G beta gamma) are capable of stimulating phospholipase C in DDT1MF-2 cell membrane preparations using lipid vesicles containing [3H]phosphatidylinositol 4,5-bisphosphate. DDT1MF-2 cell membrane and soluble fractions were found to contain phospholipase C activity which was stimulated by increases in free Ca2+ ion concentration. G beta gamma purified from bovine retinal transducin produced significant increases in phospholipase C activity in DDT1MF-2 cell membranes. G beta gamma-dependent activation of phospholipase C, while virtually absent in the presence of low Ca2+ ion concentrations, increased markedly with increasing free Ca2+ ion concentration. These data suggest that membrane bound phospholipase C in DDT1MF-2 cells is sensitive to Ca2+, and may be stimulated conditionally by G beta gamma subunits, i.e. G beta gamma subunits activate the enzyme only in the presence of Ca2+. G beta gamma subunits also stimulated soluble phospholipase C in DDT1MF-2 cells. These findings support the hypothesis that Gi beta gamma subunits are involved in adenosine A1 receptor stimulated phospholipase C/Ca2+ signaling in DDT1MF-2 cells. PMID- 7774687 TI - Functional alpha 3-glycine receptors in rat adrenal. AB - The adrenal medulla contains high-affinity strychnine binding sites, presumed to be receptors for glycine. In this study, glycine injection (400 pmol) via a cannula attached to a microdialysis probe increased in vivo concentrations of catecholamines in the adrenal microdialysate in anesthetized rats. Strychnine perfusion (20 pmol/20 min) blocked these responses. To identify receptors potentially mediating this effect, we tested for RNA transcripts of the three known alpha subunits of strychnine binding site, using the reverse transcription polymerase chain reaction. Only mRNA encoding the alpha 3 isoform was found in the rat adrenal. The findings suggest that in the rat adrenal, glycine stimulates catecholamine release by binding to strychnine binding sites and that those sites probably contain the alpha 3 isoform. PMID- 7774688 TI - [An investigation of 4,125 cases of Kazak childhood strabismus and amblyopia]. AB - An investigation was made on 4,125 Kazak pupils (aged from 4 to 14 years) with strabismus and amblyopia in 9 schools of 5 countries. Among the subjects examined, 48 cases (1.1%) were strabismus including 32 (66.67%) external and 16 (33.33%) internal strabismus; 15 cases (31.25%) suffered from both strabismus and amblyopia and 33 (68.75%) were strabismus but had normal visual acuity; 139 cases (209 eyes) were amblyopia (morbidity rate: 3.37%) including 70 binocular and 69 monocular amblyopia, 73 males and 66 females. Out of the 209 amblyopia eyes, 84 (40.19%) were slight, 104 (49.76%) medium and 21 (10.05%) serious. Ametropia was also found to be in the majority in Kazak childhood amblyope. Only 106 of 209 eyes were simple farsighted. To prevent the occurrence of amblyopia the writer suggests that efforts of finding and correcting ametropia at early stage should be made. PMID- 7774690 TI - [Primary epithelial lacrimal gland tumors: the pathologic classification of 272 cases]. AB - This paper reports the pathologic classification of 272 cases with primary epithelial lacrimal gland tumors in comparison with that of the salivary glands. The extensive series of lacrimal gland tumors accounts for 70% of the 390 lacrimal fossa lesions and 18% of the 1,530 orbital tumors in one single hospital. Benign mixed tumors ranked the first (52%), adenocystic carcinomas the second (25%) and malignant mixed tumors (9%) the third. Among the other less common tumors the authors identified, for the first time, 3 polymorphous low grade adenocarcinomas, 2 spindle celled myoepitheliomas and 1 carcinosarcoma of the lacrimal gland. The diagnosis and differential diagnosis of polymorphous low grade adenocarcinoma and spindle cell myoepithelioma were discussed. PMID- 7774689 TI - [Observations on sensory heterotropia]. AB - The authors analysed the records of 73 cases with sensory heterotropia, and discussed the correlation between the age of sensory obstacles in sensory heterotropia and the type of heterotropia, the restores of binocular vision after surgical correction and the reversion of eye position. The authors suggested that sensory heterotropia should be treated as early as possible so that binocular vision could be restored. PMID- 7774691 TI - [Eyelid reconstruction in primary position: a preliminary report of 30 cases]. AB - We performed an operation of eyelid reconstruction in primary position on 30 eyes of eyelid defect caused by different reasons. Following up for 4-24 months, there was a good result on 28 cases (93.33%). Compared with the traditional methods, the method has the characteristics of simple technic and small tissue injury. PMID- 7774694 TI - [The observation of the bulbar conjunctival microcirculation in patients with retinitis pigmentosa]. AB - The detection of the bulbar conjunctival microcirculation (BCM) of 73 cases (146 eyes) with retinitis pigmentosa (RP) showed that there were some abnormal changes of BCM in the pathologic progress of RP. The older the patient, the longer the disease history and the more the loss of visual field, the more serious the abnormal changes of BCM. The disease in male patients was in general more serious than in female patients. Its characteristics were the followings: increase in the number of tortuous vessels; the different widths of vessels in a few cases; obvious increase of microangioma; abnormal proportion of artery to vein; decelerated blood flow and aggregated erythrocytes. Some abnormal changes in the nailfold microcirculation (left ring finger) were observed in the meantime, and compared with those in the BCM of 56 cases. It was found that they were positively interrelated (gamma's = 0.9965, P < 0.001). PMID- 7774693 TI - [Haemodynamic changes and clinic significance in primary pigmentary degeneration of retina]. AB - In comparison with 40 healthy controls, the blood viscosity and erythrocystic agglutination index were predominantly higher in 44 cases with primary pigmentary degeneration. It is believed that the changes mentioned above may result in general and local circulatory disturbance, leading the tissue to ischeia, anoxia and a series of other pathological changes; and exacerbating the functional damage of retina. The author suggests that primary pigmentary degeneration of retina may be treated with the drugs which can lower the blood viscosity, the concentration of blood cholesterol and lipid, and increase blood-dynamics. PMID- 7774692 TI - [The complications of senile patients with diabetic retinopathy]. AB - From December, 1990 to June, 1992, 114 patients with diabetic retinopathy were treated ambulatorally in our department. Among them 109 cases (42 males and 67 females) were older than 45 years with 210 diseased eyes. 65 eyes suffered from simple diabetic retinopathy, 145 eyes proliferative one. The visual acuity of 105 eyes (50%) was lower than 0.3, 65 eyes (30.95%) was lower than 0.05. 100 cases (91.74%) were complicated with cardiovascular diseases, 5 cases (4.5%) with cerebrovascular accident, 56 cases (51.40%) with hyperlipemia, 42 cases (61.76%) with high viscosity of the blood. Among the ophthalmic complications, macular disease occurred in 122 eyes, cataract in 88 eyes, central retinal vein obstruction in 15 eyes, neovascular glaucoma in 5 eyes. PMID- 7774695 TI - [Treatment with Western and Chinese medicine for retinal pigmentary degeneration]. AB - The report presents 45 cases of retinal pigmentary degeneration treated by Western and Chinese medicine. Of them, 14 cases (31.11%) got significant therapeutical effectiveness; 18 cases (40%) favorite and 6 cases (13.33%) were improved. The general curative rate was 84.44%. After follow-up for 1 to 5 years, the vision and visual field in all the cases were improved to a certain extent. We used the dose of Chinese herbal medicine, the decoction of retinal pigmentary degeneration, in the treatment. The result showed it is a very beneficial method for retinal pigmentary degeneration. PMID- 7774696 TI - [Studies on MDA and MDA/MDAa in patients with retinitis pigmentosa]. AB - With fluorimetry, the concentration of malondialdehyde (MDA) and the ratio of MDA before and after the blood platelets activated (MDA/MDAa) were determined in patients with retinitis pigmentosa (RP). The results showed the above two parameters were statistically higher than those of the normal controls, which indicated the superoxidation metabolism increased and the blood was in a state of hypercoagulation in RP patients. The reasons for the results and their roles in RP disease were discussed. Treatments with anti-lipid, and anti-coagulation drugs combined with Chinese medicines were suggested. PMID- 7774697 TI - [Argon laser photocoagulation in the treatment of central serous chorioretinopathy]. AB - Thirty-six cases (41 eyes) with central serous chorioretinopathy were treated by using argon laser photocoagulation. The results showed that the number of eyes with vision equal to or more than 1.0 increased from 7 (17.1%) pre-laser to 26 (63.4%) post-laser, while the number of eyes with vision less than 1.0 decreased from 25 (61%) pre-laser to 6 (14.6%) post-laser. The subretinal fluid was almost entirely absorbed from 1 week to 1 month after, and central fovea reflex could be seen in some cases. The results indicate that the vision prognosis is strongly related to the duration of the disease, but the direction of leakage to the fovea, the distance between the leakage and the fovea, and the dimension of sensory retina detachment are factors which weakly affect the post-laser vision. PMID- 7774698 TI - [The comparative study of pattern visual evoked potential in the normal infants and adults]. AB - This paper presents the pattern visual evoked potential (PVEP) results and comparative study between the two groups of 65 normal infants at the age of 3, 6, 9, 12 months and 18 normal adults. The different pattern spatial frequency stimulations (74', 25', 6') were given to the infants and adults. In the infant group, the latencies of P1 components of PVEP delayed significantly and amplitudes of PVEP decreased significantly between 74' and 6' spatial frequency with the spatial frequency of stimulation increasing. In the same spatial frequency stimulation, when 3 months infant group was compared with the 6, 9, 12 months infant and adult groups, the latencies of N1 and P1 waves showed significant difference, but no difference was found in the amplitudes of P1 wave. Our results might indicate that the visual function expressed by low, medium, and high spatial frequency in infants from 6 to 12 months could reach the level in adults, and in 3 months infants, not maturely develop. PMID- 7774699 TI - [Study on soluble proteins in human fetal lens]. AB - Soluble proteins from corter of human fetal clear lenses were separated by column chromatography with Sepharyl S-300 (superfine) and determined by disc-PAGE and SDS-PAGE. The results documented from 18W, 21W (2 cases) and 24W fetal lenses suggested that a negative correlation tended to be presented between the age of fetus and fraction of alpha, beta 1 crystallins (r = -0.9542; r = -0.9674) and a positive correlation between the age of fetus and fraction of beta 2, gamma crystallins (r = 0.9666; r = 0.9970). There was no change in the alpha, beta 1, beta 2 crystallins on disc-PAGE. Among the fetuses of different ages, the blurred band of gamma crystallin seen in 18W and 21W fetal lenses was thickened in the 24W fetal lens. The SDS-PAGE showed that there was no significant difference among the polypeptides in each of alpha, beta 1, beta 2, gamma crystallins in the studied fetal lenses of different age groups. It is presumed that the normal lens is proportionally composed of four fractions of crystallin. This is hypothetically contributed to the maintenance of normal structure of the lens, why the proper proportion of four fractions of crystallins is depended either on proteins synthesis or on protein molecular assembly is not yet clear. PMID- 7774700 TI - [Bacteriological detection of anterior chamber aspirate after extracapsular cataract extraction with intraocular lens implantation]. AB - We cultured the anterior chamber aspirates of 83 patients with extracapsular cataract extraction and IOL implantation. Of the 83 cases, 5 (6.1%) had positive aspirates including 3 cases of staphylococcus epidermidis and 2 cases of staphylococcus aureus. No eye in our study developed bacterial endophthalmitis. Our study suggests that the anterior chamber of human eyes is capable of clearing a low inoculum of bacteria after cataract surgery without the development of bacterial endophthalmitis. PMID- 7774701 TI - [Penetrating keratoplasty for bullous keratopathy]. AB - A retrospective review for bullous keratopathy in our hospital from 1985 to 1992 was studies. Among the cases with bullous keratopathy, 14 were performed with antiglaucoma operation and cataract extraction, 12 that experienced a contusion or penetrating trauma history underwent cataract operation. IOL implantation seen in 3 patients, 4 cases were associated with vitreous contact to cornea after cataract extraction, the other 4 cases had advanced glaucoma. Besides, there were 1 case of Fuch's endothelium dystrophy, ICE syndrome and severe herpes simplex keratitis, respectively. The preoperation visual acuity of them was all less than finger count. The follow-up was 3 months to 5 years. The results showed the grafts of 28 cases (70%) were clear, 7 cases (17.5%) semi-clear, 5 cases (12.5%) opaque. Postoperatively, all of the patients escaped from the pain and 22 cases achieved a visual acuity of 0.02-0.7. Some good advice in treatment of bullous keratopathy were proposed. PMID- 7774702 TI - [Herpes zoster keratoendotheliitis]. AB - Herpes zoster keratoendotheliitis is related to autoimmunity or herpes zoster virus infection. It is characterised by K.P. and interstitial edema. The disease responds well to the administration of steroids and a good result is often achieved. PMID- 7774703 TI - [The clinical observation of China-made ofloxacin eye drops in the treatment of bacterial infection of the external eye]. AB - Ninety patients with extraocular infection were observed. After bacteriological examination on all of the patients, we found that staphylococcus epidermidis was the main pathogen and accounted for 43.3%. Next to it were staphylococcus aureus (31.1%), saprophytic staphylococcus was (5.6%), diplococcus catarrhus (3.3%) and moraxella sp. (2.2%). All the patients were treated with Ofloxacin eye drops produced in Guangzhou. The bacteriological examination showed negative in 98.9% of the patients, which proved this medicine has high antibiotic power. PMID- 7774704 TI - [Etiology of blindness in remote area: a clinic report]. AB - This paper analyzes the cause for blindness in 408 patients of Xinfeng People's Hospital from 1977 to 1991. The results show that cataract is the major cause for blindness (32.84%). The others are eye injury in patients below age 46, cataract and glaucoma in patients above age 46. It is suggested that the stress of prevention and treatment for blindness should be put on the prevention of eye injury in juveniles and middle aged people, and the treatment for senile cataract in remote mountain areas. PMID- 7774705 TI - The voltage-gated Ca2+ release channel in the vacuolar membrane of sugar beet resides in two activity states. AB - The voltage-gated Ca2+ release channel in the vacuolar membrane of sugar beet tap roots resides in two states which show similar reversal potentials in biionic conditions but differ dramatically in their single channel current and open frequency. State I has a unitary Ca2+ conductance of 3.9 +/- 0.5 pS and channel openings are rare at vacuolar resting potentials. After spontaneous and reversible transition into State II the unitary Ca2+ conductance increases three fold, accompanied by a concomitant rise in channel activity over the physiological voltage range. The 15- to 19-fold increase in total Ca2+ current after the State I to State II transition could play an essential role in channel activation during signal transduction. PMID- 7774706 TI - Differential regulation of G protein alpha-subunit GTPase activity by peptides derived from the third cytoplasmic loop of the alpha 2-adrenergic receptor. AB - The effect of peptides homologous to segments of a G protein-coupled receptor on the GTPase activity of recombinant Go alpha (rGo alpha) and Gs alpha (rGs alpha) has been tested. These peptides contain overlapping sequences spanning from amino acid 212 of the putative fifth transmembrane domain to amino acid 229 of the third cytoplasmic loop of the alpha 2 adrenergic receptor. Interestingly, two peptides (comprising residues 212-227 and 214-227) strongly inhibit the basal GTPase activity of both rGo alpha and rGs alpha. Instead, a C-terminally extended peptide (residues 216-229) stimulates rGo alpha but slightly inhibits rGs alpha. Circular dichroism spectroscopy of the peptides reveals that an a helical structure is more easily inducible in the inhibitory ones. These findings constitute an example of peptides representing cytoplasmic receptor sequences that differentially modulate the GTPase activity of recombinant G protein alpha subunits. PMID- 7774707 TI - Amiloride and harmaline are potent inhibitors of NhaB, a Na+/H+ antiporter from Escherichia coli. AB - The diuretic drug amiloride is a specific inhibitor of sodium transporting proteins in several cell types. Attempts to inhibit this activity in membrane vesicles derived from various bacteria, did not yield clear results. Therefore, we tested the effect of amiloride and its derivatives on the purified Na+/H+ antiporters of E. coli reconstituted in functional form in proteoliposomes. Whereas NhaA is not inhibited by amiloride, both amiloride and harmaline are potent inhibitors of NhaB with K0.5 of 6 and 15 microM, respectively. The pattern of inhibition by amiloride derivatives is different from that reported for mammalian antiporters but similar to that reported for the Na+/H+ antiporter of D. salina [Katz, A., Kleyman, T.R. and Pick, U. (1994) Biochemistry 33, 2389 2393]. Clonidine is a poor inhibitor (K0.5 = 200 microM) while cimetidine had no effect on the antiporter up to concentration of 1 mM. These new potent inhibitors provide us with important tools for the study of the mechanism of action of NhaB. PMID- 7774708 TI - Lutein associated with a transthyretin indicates carotenoid derivation and novel multiplicity of transthyretin ligands. AB - Transthyretins isolated from different species bind hydrophobic compounds and are often obtained in a yellow form. Such a transthyretin from chicken serum was purified by chromatography using Sepharose-coupled human retinol-binding protein. The yellow chromophore was extracted with methanol and purified by reverse phase HPLC followed by normal-phase chromatography on a nitrile column. Ultraviolet visible absorbance and mass spectrometry identified the yellow compound as lutein, i.e. xanthophyll, (all-trans)-beta, epsilon-carotene-3,3'-diol, estimated to constitute 10-30% of associated colourless compounds. These components are different from the yellow component isolated from human transthyretin and establish that carotenoid-derived pigments can be associated with transthyretins. PMID- 7774709 TI - Phospholipid membrane permeability of peptide nucleic acid. AB - Phospholipid vesicles (liposomes) as membrane models have been used to study the penetration properties of peptide nucleic acid (PNA), a new DNA analog in which the nucleobases are attached to a pseudo-peptide backbone. The liposomes were characterised by carboxyfluorescein efflux, light-scattering and cryogenic transmission electron microscopy. The liposome structure was found not to be affected by the incorporation of PNA or an oligonucleotide. Two 10-mer fluorescein-labelled PNAs were found to have low efflux rates (half-times of 5.5 and 11 days), comparable to a 10-mer oligonucleotide (half-time of 7 days). We conclude that passive diffusion of unmodified PNA is not an effective way of transport into biological cells. PMID- 7774710 TI - Two molecules of cytochrome c function as the electron donors to P840 in the reaction center complex isolated from a green sulfur bacterium, Chlorobium tepidum. AB - A photoactive reaction center complex was isolated from a thermophilic green sulfur bacterium, Chlorobium tepidum under anaerobic conditions. The electron transfer occurred from heme c to the photo-oxidized reaction center chlorophyll, P840+, with a half time (t1/2) of 110 or 340 microseconds at 24 or 12 degrees C, respectively. Optical measurements under multiflash excitations indicated that two hemes function as the immediate electron donors to P840+. SDS-PAGE analysis of the RC complex in combination with the N-terminal amino acid sequence analyses revealed five subunit bands; a core protein (65 kDa), the light harvesting bacteriochlorophyll alpha protein (41 kDa), a protein with 2[4Fe-4S] clusters (31 kDa), monoheme cytochrome c (22 kDa), and a 18-kDa protein whose function is unknown. The reaction center complex, thus, contains two molecules of cytochrome c per P840. PMID- 7774712 TI - Stimulation of MAP kinase by v-raf transformation of fibroblasts fails to induce hyperphosphorylation of transfected tau. AB - A proportion of the microtubule-associated protein, tau, is in an elevated state of phosphorylation in foetal and adult brain whereas all of the tau in paired helical filaments, which are characteristic of Alzheimer's disease is hyperphosphorylated; it is important therefore to elucidate the mechanisms that regulate tau phosphorylation. Here we describe results that show that although MAP kinase can hyperphosphorylate tau in vitro, activation of MAP kinase in transformed fibroblasts does not result in hyperphosphorylation of transfected tau, whereas glycogen synthase kinase-3 beta (GSK-3 beta) when co-transfected with tau does result in tau hyperphosphorylation. The findings imply that GSK-3 beta may be a stronger candidate than MAP kinase for inducing tau hyperphosphorylation in vivo. PMID- 7774711 TI - Complete 13C assignments for recombinant Cu(I) rusticyanin. Prediction of secondary structure from patterns of chemical shifts. AB - Complete resonance assignments for the 13C spectrum of reduced (Cu(I)) rusticyanin have been made using 13C, 15N doubly labeled recombinant material. The reported assignments include those for the carboxyl and carbonyl carbon atoms and protonated aromatic ring carbons, and were obtained using a variety of 2- and 3D inverse-detected NMR experiments, including 13C, 15N, 1H triple resonance experiments and HCCH-COSY and -TOCSY. Backbone carbonyl assignments were obtained using 3D HNCO and HCACO spectra, and modified versions of 2D H(CA)CO and HMBC spectra were used to obtain side-chain carboxyl carbon and methionine epsilon methyl carbon assignments, respectively. A comparison of the 13C alpha, 13C beta and 13CO chemical shifts with published 'random coil' values confirms the conclusion reached from a consideration of the 3JHN alpha coupling constants and the pattern of sequential NOEs, that the protein consists largely of beta structure. PMID- 7774713 TI - The amino acid sequence of eukaryotic translation initiation factor 1 and its similarity to yeast initiation factor SUI1. AB - Eukaryotic initiation factor eIF-1 was purified from rabbit reticulocytes. Amino acid sequence analysis revealed that the protein contained a blocked amino terminus. After cleavage with the endoproteinase Asp-N, three peptides were sequenced. The obtained partial sequences were identical to sequences of SUI1ISO1, the human homologue of the yeast translation initiation factor SUI1. The SUI1 gene product was identified as a protein involved in the recognition of the protein synthesis initiation codon. A similar mode of action has been suggested for eIF-1. PMID- 7774714 TI - Cell adhesion activity of the short cytoplasmic domain isoform of C-CAM (C-CAM2) in CHO cells. AB - C-CAM is a Ca(2+)-independent rat cell adhesion molecule belonging to the CEA gene family of the immunoglobulin superfamily. Two major isoforms that differ in the length of their cytoplasmic domains exist. In previous studies it has been reported that only the long isoform (C-CAM1) but not the short isoform (C-CAM2) can mediate adhesion. However, in the mouse, isoforms with both long and short cytoplasmic domains have been reported to have adhesive activity. In order to analyze this apparent conflict we transfected C-CAM1 or C-CAM2 into CHO Pro5 cells and examined their adhesive phenotype in an aggregation assay. We found that in this cellular system both C-CAM1 and C-CAM2 could mediate cell-cell adhesion in a Ca(2+)-independent and temperature-independent way. The results suggest that the cellular environment is important for the activity of C-CAM isoforms. PMID- 7774715 TI - Structural determination of two N-linked glycans isolated from recombinant human lactoferrin expressed in BHK cells. AB - A full-length cDNA coding for human lactoferrin was isolated from a mammary gland library and the recombinant protein was expressed in BHK cells as described by Stowell K. M. et al. [1991, Biochem. J. 276, 349-355]. Two N-linked glycans from purified recombinant lactoferrin were released by hydrazinolysis and analyzed by 400-MHz 1H-NMR spectroscopy. The identified structures corresponded to N acetyllactosaminic biantennary glycans and were alpha-2,3-disialylated forms (80%) or alpha-2,3-monosialylated (20%) forms. Moreover, 70% of total glycans were alpha-1,6-fucosylated at the GlcNAc residue linked to asparagine. In regard to its glycan moiety, the recombinant glycoprotein is close to native lactoferrins from milk or leucocytes but shows specific structural features which should be taken into account prior to in vivo and in vitro biological studies. PMID- 7774716 TI - Regulation of the human spermidine synthase mRNA translation by its 5' untranslated region. AB - An increased mRNA content of spermidine synthase was found in phytohemagglutinin stimulated human peripheral lymphocytes and in cultured human myeloma (Sultan) cells stimulated to grow by change of the culture medium. The many-fold increase in the amount of the message was accompanied by stimulation of the enzyme activity in activated lymphocytes, but not in stimulated myeloma cells. In the present study the effect of the 5'-untranslated region of spermidine synthase mRNA on the post-transcriptional control of its expression was studied both in vitro in rabbit reticulocyte system and in cultured mammalian cells. The results show that the GC-rich 5'-untranslated region of spermidine synthase mRNA has an inhibitory effect on its translation. PMID- 7774717 TI - Lipid hydroperoxide-induced apoptosis: lack of inhibition by Bcl-2 over expression. AB - Increased membrane lipid peroxidation has recently been implicated as being associated with apoptosis. In the present study the addition of 15 hydroperoxyeicosatetraenoic acid (15-HPETE) or 13-hydroperoxydodecadienoic acid (13-HPODE) to A3.01 T cells is shown to induce marked chromatin condensation coincident with DNA fragmentation, indicative of apoptosis. 15-HPETE also evoked an immediate and sustained rise in cytoplasmic calcium which was required for the induction of apoptosis. A3.01 cells transfected with the bcl-2 proto-oncogene were 6- to 8-fold more resistant to apoptotic killing by tumor necrosis factor alpha, but only 0.4-fold more resistant to 15-HPETE. Thus, Bcl-2 is not capable of protecting cells from undergoing apoptosis following the direct addition of lipid hydroperoxides. PMID- 7774718 TI - Effect of 6-ketocholestanol on FCCP- and DNP-induced uncoupling in plant mitochondria. AB - Effect of 6-ketocholestanol on FCCP-induced and DNP-induced uncoupling in beef liver and pea stem mitochondria was studied, under experimental conditions at which this steroid abolished the effect of low concentrations of FCCP and other most potent uncouplers in rat mitochondria [Starkov et al. (1994) FEBS Lett., 355, 305-308]. It is shown that, in both types of mitochondria, 6-ketocholestanol prevents or reverses the uncoupling induced by low concentrations of FCCP, but not that caused by high concentrations of FCCP or by any concentration of DNP. Progesterone and male sex hormones, showing recoupling capability in animal mitochondria, appear to be ineffective in the plant system. Cholesterol does not recouple in both animal and plant mitochondria. Plant steroids, such as beta sitosterol and stigmasterol, are also without effect. PMID- 7774719 TI - Homologues of the engrailed gene from five molluscan classes. AB - We used the polymerase chain reaction (PCR) to amplify, clone, and sequence 10 engrailed homeodomains from 8 species in the five major molluscan classes, including the serially organized chiton (Polyplacophora) lineage. The Drosophila melanogaster gene engrailed (en) is one of several genes involved in embryonic segment polarity determination. Studies of engrailed sequence and expression in molluscs are of interest due to questions regarding the evolution and homology of segmentation in these taxa. Nucleotide and deduced amino acid sequence comparisons reflect evolutionary conservation within helices of the en homeodomain and ancient divergences in the region 3' to the homeodomain. PMID- 7774721 TI - Wild type and constitutively activated forms of the Drosophila Toll receptor have different patterns of N-linked glycosylation. AB - Toll is a Drosophila membrane protein related in sequence to the mammalian platelet glycoprotein 1B and to the interleukin-1 receptor. It mediates a signal transduction pathway leading to the development of dorsoventral polarity in the Drosophila embryo. In this paper we show that a constitutively activated mutant receptor, Toll10B, is processed into a distinct isoform of slower electrophoretic mobility when compared with the wild type molecule in both cell lines and the embryo. The wild type protein can also be processed into this form if over expressed but in the embryo is present as the smaller species. We show that the decrease in the mobility of Toll10B and over-expressed wild type receptors is caused by altered patterns of N-linked glycosylation and that both forms are secreted to the cell surface. On the basis of these results, we propose that the Toll10B receptor is unable to associate with a limiting co-factor which when bound directly or indirectly masks supplementary N-linked glycosylation sites. PMID- 7774720 TI - Conversion of the sodium channel activator aconitine into a potent alpha 7 selective nicotinic ligand. AB - Methyllycaconitine (MLA) is a competitive antagonist of nicotinic acetylcholine receptors, with a remarkable preference for neuronal [125I]alpha Bgt binding sites. We have begun to investigate the structural basis of its potency and subtype selectivity. MLA is a substituted norditerpenoid alkaloid linked to a 2 (methylsuccinimido)benzoyl moiety. Hydrolysis of the ester bond in MLA to produce lycoctonine diminished affinity for rat brain [125I]alpha Bgt binding sites 2500 fold and abolished affinity for [3H]nicotine and muscle [125I]alpha Bgt binding sites. The voltage-gated Na+ channel activator aconitine, also a norditerpenoid alkaloid, but with significant structural differences from lycoctonine, displayed comparable weak or absent nicotinic activity. Addition of a 2 (methylsuccinimido)benzoyl sidechain to O-demethylated aconitine, to mimic MLA, abolished Na+ channel activation and conferred nanomolar affinity for brain [125I]alpha Bgt binding sites, comparable to that of MLA. We propose that the ester-linked 2-(methylsuccinimido)benzoyl group is necessary for nicotinic potency, but alpha 7 selectivity resides in the norditerpenoid core of the molecule. PMID- 7774722 TI - Interferon receptor recognition peptides enhance the biological potency of interferon alphas. AB - Based on our earlier studies that defined three strategic regions in the Type 1 interferon (IFN) molecule associated with receptor interactions and biological activity, three IFN receptor recognition peptides (IRRP) were synthesized, with amino acid sequences CLKDRHD (IRRP1), ESLLEKFYTELYQQLND (IRRP2) and YFQRITLYLTEKKYSPCA (IRRP3) and examined for biological effectiveness. In cell surface receptor binding studies, the binding capacity of cells for IFN-alpha s was increased in the presence of the IRRPs. Increased receptor occupancy resulted in increased phosphorylation-activation of the transcription factor ISGF3 and enhanced antiviral activity. The potentiating effect on IFN-induced growth inhibition was less marked. These data suggest that the IRRPs may influence the biological potency of IFN-alpha by facilitating accessibility to cell surface receptor components. The IRRPs may function to increase the number of low affinity receptor-ligand interactions necessary to initiate receptor oligomerization, thereby catalysing the formation of high affinity IFN-receptor complexes. PMID- 7774723 TI - Introduction of a CuA site into the blue copper protein amicyanin from Thiobacillus versutus. AB - The C-terminal loop of the blue copper protein amicyanin, which contains three of the four active site ligands, has been replaced with a CuA binding loop. The purple protein produced has visible and EPR spectra identical to those of a CuA centre. Recent evidence strongly suggests that the CuA centre of cytochrome c oxidase and the A centre of nitrous oxide reductase are similar and are both binuclear. It therefore follows that the purple amicyanin mutant created here also possesses a binuclear CuA centre. PMID- 7774724 TI - Furin is important but not essential for the proteolytic maturation of gp160 of HIV-1. AB - The envelope glycoproteins of HIV are required for viral infectivity. Proteolysis of the precursor envelope glycoprotein gp160 results in the formation of gp120 and gp41. Cleavage occurs after the sequence Arg-Glu-Lys-Arg. This sequence is expected to be a substrate for the cellular protease furin. We examined whether furin is responsible for cleavage of gp160 by using a furin-deficient CHO cell line and the same cell line transfected with furin cDNA. Data obtained from viral transmission assays suggested that furin increased viral infectivity but was not essential for the maturation of gp160, implying that other proprotein processing enzymes also recognize this putative furin cleavage site. PMID- 7774725 TI - Amylin and epinephrine have no direct effect on glucose transport in isolated rat soleus muscle. AB - Amylin and epinephrine did not significantly affect insulin stimulated, or basal, 3-O-methylglucose transport in isolated rat soleus muscle, as measured by the release of 3-O-methylglucose from pre-loaded tissue. Both amylin and epinephrine inhibited insulin-stimulated 2-deoxyglucose uptake (by 25% and 38%, respectively) in soleus muscle from fed rats but not from fasted rats. The latter results are consistent with amylin and epinephrine stimulating glycogenolysis and inhibiting hexokinase activity by intracellular accumulation of glucose 6-phosphate. We conclude that amylin, like epinephrine, does not specifically inhibit glucose transporters in skeletal muscle. PMID- 7774726 TI - Estimates of early twentieth-century U.S. homicide rates: an econometric forecasting approach. AB - Bureau of the Census death registration records, as reported in Mortality Statistics, are a primary source for early twentieth-century U.S. homicide statistics. Those data appear to show a massive rise in homicide during the first decade of the century, with a continuing increase through 1933. This increase is quite at variance with the trend away from violence in other industrialized societies. During the first one-third of the century, however, death registration was incomplete; it occurred only in an expanding "registration area" that was composed, in the earlier years, primarily of states with typically low rates of homicide. Further, in the first decade of the century homicides within the registration area often were reported as accidental deaths. As a result, apparent increases in rates of homicide in the United States between 1900 and 1933 may be illusory. I use a two-step process to address these problems. Drawing on internal evidence and commentaries in early volumes of Mortality Statistics, I use GLS regression to estimate the prevalence of undercounts. Then I create a series of GLS models that use registration area data to estimate early twentieth-century national rates. These estimates call into question the extent of homicide change early in the century. PMID- 7774727 TI - Binary outcomes and endogenous explanatory variables: tests and solutions with an application to the demand for contraceptive use in Tunisia. AB - Many demographic studies examine discrete outcomes, and researchers often suspect that some of the explanatory variables may be influenced by the same unobserved factors that determine the discrete outcome under examination. In linear models, the standard solution to this potential endogeneity bias is an estimator such as two-stage least squares. These methods have been extended to models with limited dependent variables, but there is little information on the performance of the methods in the types of data sets typically used in demographic research. This paper helps to fill this gap. It describes a simple analytic framework for estimating the effects of explanatory variables on discrete outcomes, which controls for the potential endogeneity of explanatory variables. It also discusses tests for exogeneity and joint determination of the outcomes and the explanatory variables. It summarizes the results of a Monte Carlo study of the performance of these techniques and uses these results to suggest how researchers should approach these problems in practice. We apply these methods to the examination of the impact of fertility intentions on contraceptive use, based on data from the 1988 Tunisia Demographic and Health Survey. PMID- 7774728 TI - Echoes of the baby boom and bust: recent and prospective changes in living alone among elderly widows in the United States. AB - Today the great majority of noninstitutionalized elderly widows live alone, a striking increase from a quarter-century ago. A noticeable difference has occurred, however, in trends by age; the proportion of the young-old widows living alone is starting to decline, while that of the old-old continues to increase. We use a model suggested by earlier studies to explain the emergence of this difference, and assess the prospects of its continuing over the next three decades. We find that the recent differential change in the proportions of younger and older widows living alone is due primarily to a differential change in kin availability that has emerged as the baby boomers' parents have begun to reach retirement age. Over the next decade, the same type of differential change by age in kin availability will continue; living alone is likely to become less common among young-old than among old-old widows, in a reversal of the pattern of the last quarter-century. In the first two decades of the next century, as the baby boom affects kin availability among the old-old, and as the subsequent baby bust affects that among the young-old, the age pattern of living arrangements among elderly widows will reverse once again. PMID- 7774729 TI - Stability and change in temporal distance between the elderly and their children. AB - Drawing on a developmental model of late-life migration, this paper investigates how older people's health and social characteristics influence stability and change in their temporal distance from their children. Data from the Longitudinal Study of Aging are used to examine both discrete transitions and continuous change in distance over a four-year period. Decline in older parents' physical health increased the propensity of parents and children to become temporally closer to each other. Among those parent-child pairs who had become closer, the conjunction of declining health and widowhood increased both the degree of non coresident proximity and the likelihood of transition to coresidence. The findings portray a geographically resilient family that adjusts to the changing needs of its older members. PMID- 7774730 TI - The influence of nonmarital childbearing on the formation of first marriages. AB - We document a negative association between nonmarital childbearing and the subsequent likelihood of first marriage in the United States, controlling for a variety of potentially confounding influences. Nonmarital childbearing does not appear to be driven by low expectations of future marriage. Rather, it tends to be an unexpected and unwanted event, whose effects on a woman's subsequent likelihood of first marriage are negative on balance. We find that women who bear a child outside marriage and who receive welfare have a particularly low probability of marrying subsequently, although there is no evidence that AFDC recipients have lower expectations of marriage. In addition, we find no evidence that stigma associated with nonmarital childbearing plays an important role in this process or that the demands of children significantly reduce unmarried mothers' time for marriage market activities. PMID- 7774731 TI - The impact of "parent care" on female labor supply decisions. AB - Data from the 1986-1988 Survey of Income and Program Participation panels were used to analyze how informal caregiving of disabled elderly parents affected female labor supply. Instrumental variables analyses suggested that coresidence with a disabled parent leads to a large, significant reduction in work hours, due primarily to withdrawal from the labor force. Although the impact of nonhousehold member caregiving was insignificant, evidence of an effect was stronger when commitment of caregiving time was greater. Projections of female labor force participation rates should account for potential increases in caregiving demand due to the aging of the U.S. population. PMID- 7774732 TI - Measuring fertility demand. AB - We propose a multidimensional conceptualization of fertility demand and evaluate potential measures of each dimension, using data from a telephone survey of Wisconsin residents age 18-34. Most of the measures met tests for interval-level measurement; all produced high estimates of test-retest reliability. We found support for only two dimensions of demand, intensity and certainty; potential measures of centrality had relatively low associations with any of the latent dimensions. Demand certainty improved prediction of fertility expectations beyond a trichotomous (yes, no, don't know) measure, but demand intensity did not. We found mixed evidence for the conceptualization of fertility demand as a single continuum on which desire to avoid pregnancy is the opposite of desire to have a child. PMID- 7774733 TI - Redefining single-parent families: cohabitation and changing family reality. AB - This paper explores the implications, for the measured prevalence and duration of mother-only families, of marked changes in nonmarital fertility, unmarried cohabitation, and homeleaving and re-entry. Throughout, estimates are compared on the basis of marital definitions and definitions including cohabitation. The duration of the first single-parent spell appears to have increased under the marital definition, but declines substantially when cohabitations are taken into account. A substantial proportion of single mothers have spent some time as single parents while in their parents' household. Hence we argue that definitions of single-parent families must be based on living arrangements rather than on the parents' marital status. PMID- 7774734 TI - Adolescent gynecology and obstetrics. AB - Adolescent gynecology is a subspeciality of obstetrics and gynecology and not broadly known. It deals with many gynecological and obstetrical problems which may be seen during adolescence. The International Federation of Pediatric and Adolescent Gynecology is a branch of FIGO and promotes research and teaching programs on pediatric and adolescent gynecology. Health care professionals should address sex education programs providing accurate information to young people on sexual matters. Prevention of gynecological diseases, undesired pregnancies and sexually transmitted diseases are the goals of physicians working in adolescent gynecology. PMID- 7774735 TI - A randomized prospective trial comparing single dose prostaglandin E2 vaginal gel with forewater amniotomy for induction of labour. AB - A prospective randomized parallel-group study was carried out to compare the efficacy of a single dose vaginal prostaglandin E2 gel with forewater amniotomy for induction of labour at term in 260 parturients (110 primigravid and 150 parous women) with low risk pregnancy and favourable cervix. In the prostaglandin E2 (PGE2) managed group, the primigravidae were treated with 2 mg PGE2 gel and parous patients with 1 mg PGE2 gel. Forewater amniotomy was performed 4 h later, or sooner if women requested analgesia. In the amniotomy group, artificial forewater amniotomy was carried out and a repeat cervical assessment done 4 h later, or sooner if women requested analgesia. In both groups, intravenous oxytocin was established if there was evidence of disordered uterine activity, 6 h after the start of initial intervention. An assessment of consumers' views was carried out by using a standardized questionnaire completed 48 h after delivery. There was a significant reduction in the requirement for oxytocin augmentation in women treated with PGE2: primigravidae, odds ratio (OR), 0.27 and 95% confidence interval (CI), 0.12-0.61; multiparae, OR, 0.19 and 95% CI, 0.08-0.45. Fewer primigravidae managed with PGE2 gel required epidural analgesia (OR, 0.16; 95% CI, 0.06-1.00). Fewer parous women managed with PGE2 gel required parenteral opiates (OR, 0.44; 95% CI, 0.23-0.85) and more women required inhalation analgesia or no analgesia (OR, 2.22; 95% CI, 1.76-2.79). The intervention to delivery intervals were shortened in PGE2 groups independent of parity but the differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774737 TI - Amniocentesis before 15 weeks' gestation: technical aspects and obstetric risks. AB - In a prospective case-control study, early amniocenteses (EAC, n = 242) at between 12 and 14 weeks gestation, were compared with standard amniocenteses (SAC, n = 242) performed at between 15 and 24 weeks gestation. The medical records of these 484 cases were reviewed for indications, success rate, color and volume of amniotic fluid, gestational age, number of needle insertions, location of the placenta, culture failure rate, obstetric complications and therapeutic abortion rate. There were no significant differences between the two groups in success rate, in culture success rate or in the outcome of the pregnancies. The volume of the sample taken was smaller in the EAC patients (P < 0.001), and therapeutic abortions were performed significantly earlier (P < 0.02.) Results show that EAC is feasible from 11 weeks' gestation, and can be performed for the usual indications as an alternative to chorionic villus sampling. In the near future, cytogenetic techniques will enable results to be obtained in less than a week. PMID- 7774736 TI - Induction of labour at term in primigravidae with low Bishop's score: a comparison of three methods. AB - OBJECTIVE: To determine which of three methods of induction of labour at term in primigravidae with a low Bishop's score is effective and safe. DESIGN: Random allocation to Prostin E2 and amniotomy later (Group A); low amniotomy and oxytocin titration (Group B); and intra-cervical Foley balloon overnight followed next morning by low amniotomy and oxytocin titration (Group C). SUBJECTS AND SETTING: Primigravidae (n = 90) in the University Hospitals, Benin City, Nigeria. MAIN OUTCOME MEASURE: (i) Time taken to achieve 3 uterine contractions in 10 min; (ii) induction-delivery interval. RESULTS: The mean time interval between intervention and regular uterine contractions was shortest in Group C (A vs. C, P < 0.02; A vs. B, P < 0.02). The mean induction-delivery interval was shortest in Group C (11.1 h) followed by Group B (13.9 h) and Group C (17.9 h) P < 0.05 0.001. CONCLUSION: The induction-delivery interval was shortest when using a Foley catheter for cervical ripening followed by amniotomy and oxytocin titration. PMID- 7774739 TI - Obstetric and perinatal outcome in human immunodeficiency virus-infected pregnant women with and without opiate addiction. AB - This study was undertaken to assess the impact on gestation played by the simple human immunodeficiency virus (HIV)-seropositive status either alone or complicated by opiate abuse in the absence of other confounding variables. To this purpose the main obstetric complications and the perinatal outcome were prospectively evaluated in 38 simple HIV-infected women, 14 of whom were simple carriers and 24 under methadone treatment, and in 76 uninfected women, 16 of whom were methadone users and 60 controls. In simple HIV-carriers maternal weight gain (P < 0.001) and both 1- and 5-min Apgar scores (P < 0.005) were reduced whereas the incidence of miscarriage was increased (P < 0.05). Worse obstetric and perinatal outcomes were found in HIV-seropositive drug addicts, in which gestational length (P < 0.001), maternal weight gain (P < 0.001) and Apgar scores were lower (P < 0.005 and P < 0.001, respectively) and the rate of preterm labour, small for gestational age newborns, vaginal and urinary infections as well as of unexplained fever (P < 0.05) was higher. Outcomes were similar in HIV seropositive and seronegative drug addicts and in both groups a positive correlation (r = 0.62 P < 0.001, and r = 0.44, respectively) was found between the number of infectious episodes throughout pregnancy and the mean dose of opiate consumed daily. Our results suggest that HIV-seropositive condition might exert slight direct and indirect detrimental effects on pregnancy. Whatever the maternal serologic status, opiate intake not only causes a further worsening of gestational and perinatal outcomes, but also increases the susceptibility towards pathogens. PMID- 7774738 TI - Perinatal mortality in home births in rural Tanzania. AB - OBJECTIVE: To compare perinatal mortality, stratified for risk level, in home births attended by a relative or traditional birth attendant without formal training with births attended by trained personnel in a dispensary or hospital. STUDY DESIGN: A prospective community based study in five villages in Northwestern Tanzania during 1990, involving 222 women delivering at home and 199 in a dispensary or hospital. RESULTS: Twenty-two of the 29 (76%) perinatal deaths occurred in home births. Perinatal mortality, stratified for risk level, was three times higher in home births than it was in births in dispensaries or in hospital (Mantel-Haenszel odds ratio, 3.29; 95% CI, 1.28-9.22). CONCLUSIONS: This study re-emphasises that all births should be attended by adequately trained personnel. More effective strategies are needed to convince women with high risk pregnancies to deliver in hospital. Emergency referral services are required to deal with unexpected complications arising in low risk births at home. PMID- 7774740 TI - Peripheral capillaroscopic findings and blood rheology during normal pregnancy. AB - Peripheral capillary microscopy and blood rheology where used to investigate circulatory changes during normal pregnancy. The first part of the investigation was designed as a cross-sectional study in which capillary morphology and blood flow in the first (n = 24) and third trimester (n = 15) of pregnancy was compared with non-pregnant controls (n = 15). In the second part a longitudinal comparison of capillaroscopic and hemorheological findings throughout pregnancy was performed in 12 women with four measurements at 10-week intervals. In addition, in this group hemorheological measurements were carried out. Both the cross sectional as well as the longitudinal group showed a significant increase in capillary blood flow velocity which was already present in the first trimester. Throughout pregnancy a gradual enlargement of the pericapillar papilla was seen, reflecting water retention in the interstitial tissue. At low shear rates a significant increase in viscosity was found at the end of pregnancy both in whole blood and at a standardized hematocrit of 45%. Capillaroscopy appears to be an appropriate method to study circulatory changes throughout pregnancy and its value as a diagnostic tool to detect early pathological developments is the objective of a future investigation. PMID- 7774741 TI - Abu Dhabi third stage trial: oxytocin versus Syntometrine in the active management of the third stage of labour. AB - OBJECTIVE: To compare the effect of oxytocin and Syntometrine when used as part of active management of third stage of labour on postpartum haemorrhage, hypertension, nausea/vomiting and retained placenta. STUDY DESIGN: A randomised double blind trial was conducted in the Obstetric Unit of Corniche Hospital, Abu Dhabi in the United Arab Emirates. Between 1 January 1991 and 30 June 1991, 2040 women were randomly allocated either to the oxytocin (n = 1017) or the Syntometrine (n = 1023) group. Twelve patients had to be excluded from the trial (oxytocin, 5; Syntometrine, 7) after randomisation because they no longer fulfilled the inclusion criteria. All women in the trial received either oxytocin 10 units or Syntometrine 1 ml (oxytocin 5 units+ergometrine (ergonovine) 0.5 mg) by intramuscular injection with delivery of the anterior shoulder of the baby. Relative risk with 95% confidence intervals was calculated for each variable. RESULTS: Oxytocin (10 units) alone was as effective as Syntometrine (1 ml) in preventing post-partum haemorrhage without an increase in the incidence of retained placenta. Median blood loss was similar in both groups. The incidences of nausea, vomiting and headache were significantly lower in the oxytocin group, as was the occurrence of a mean rise in diastolic and systolic blood pressures of 20 and 30 mmHg or more, respectively. CONCLUSION: Prophylactic administration of oxytocin 10 U in the third stage of labour, as part of active management, reduces the incidence of maternal nausea, vomiting, headache and rise in blood pressure than does Syntometrine 1 ml without adversely affecting the rate of post partum haemorrhage. PMID- 7774742 TI - The karyotype of fetuses with anomalies detected by second trimester ultrasonography. AB - OBJECTIVE: To determine the incidence of abnormal karyotype among fetuses with anomalies detected by detailed second trimester ultrasonography. STUDY DESIGN: A total of 573 patients underwent amniocentesis following the detection of anomalies by detailed second trimester ultrasonography. RESULTS: Thirty-six (6.3%) fetuses with abnormal karyotype were detected. The most common abnormal karyotypes were: trisomy 18, 11 cases; trisomy 21, 8 cases; 45XO, 7 cases; trisomy 13, 3 cases; and triploidy, 2 cases. Abnormal karyotype was detected in 20/111 (18%) fetuses with more than one anomaly, 15/182 (8.2%) with cystic hygroma, and 1/38 with nuchal thickening. No abnormal karyotype was detected among 108 fetuses with choroid plexus cyst, 58 with hydronephrosis, 25 with ventriculomegaly, 16 with a single umbilical artery, 18 with cardiac anomalies. CONCLUSIONS: (1) Half of the cases with abnormal karyotype occurred in fetuses with more than one anomaly. (2) Cystic hygroma was the isolated malformations most commonly associated with abnormal karyotype. (3) Isolated malformations such as choroid plexus cyst or hydronephrosis were not associated with abnormal karyotype. PMID- 7774743 TI - Successful external version of B-twin after the birth of A-twin for vertex--non vertex twins. AB - OBJECTIVE: To determine the optimal intrapartum management of twins, especially those in vertex--non-vertex presentation. STUDY DESIGN: The study population consisted of 408 sets of twins delivered between 1988 and 1992, weighing at birth over 1500 g. According to our protocol, vaginal delivery was attempted in the vertex-vertex presentations. If non-vertex presentation was first, we performed cesarean section. In vertex--non-vertex cases, the first was delivered vaginally and external cephalic version or breech delivery was performed on the second. Apgar scores were compared according to presentation and delivery mode. RESULTS: Vaginal delivery was accomplished in 122 (73%) of 169 vertex--vertex presentations, 96 (68%) of 142 vertex--non-vertex presentations, and 4 (5%) of 99 non-vertex--other presentations. External cephalic version (ECV) of the second twin and subsequent vaginal delivery in vertex--non-vertex was successful in 75% of cases, and internal podalic version and assisted breech delivery were performed in 20 cases, and the remaining two were delivered by cesarean section. Apgar scores were not significantly different among the various groups, and no complications arose from external cephalic version performed on second non-vertex twins. CONCLUSIONS: External cephalic version was found safe for delivering second non-vertex twins in cases where the first twin is in vertex presentation. In our opinion routine cesarean section is thus no longer justified in such cases. PMID- 7774744 TI - Transvaginal sonography and endometrial thickness in patients with postmenopausal uterine bleeding. AB - The objective of the present study was to evaluate the usefulness of transvaginal ultrasonography in assessment of the endometrial thickness in patients with postmenopausal uterine bleeding in relation to the histopathological results of the endometrial biopsy. A total of 118 women with postmenopausal uterine bleeding were studied prospectively. Thirty postmenopausal women without vaginal bleeding and without gynaecological complaints served as a control group. In women with histopathological diagnosis of atrophic endometrium the mean endometrial thickness was 3.1 +/- 1.7 mm whereas the corresponding value for patients with endometrial carcinoma was 18.4 +/- 8.2 mm (P < 0.001). No endometrial carcinoma was diagnosed in endometrial thickness < or = 6 mm. The sensitivity was 100% and specificity 64% if a 6-mm cutoff limit was used. We consider that transvaginal ultrasonographic investigation for post-menopausal bleeding may provide useful information for selection of those patients who are under higher risk of endometrial abnormalities. When using vaginal sonography for measuring the endometrial thickness in women with postmenopausal bleeding, it is reasonable not to perform a dilatation and curettage if the endometrial thickness is < or = 6 mm. PMID- 7774745 TI - The omentoplasty: a neglected ally in gynecologic surgery. AB - Although the omentum is extensively used in general, reconstructive and thoracic surgery as a pedicled omentoplasty, little information exists about the utility of such a procedure in general and radical gynecologic surgery. In this paper we review the properties of the omentum which may be useful in gynecologic surgery. The omentum is highly vasculated and rich in thromboplastin, an excellent property for treating difficult to handle abdominal or pelvic abscesses and for inducing hemostasis. Furthermore, it appears that the omentum has a trophical effect on the surrounding tissue, making it very useful in reconstruction procedures. Moreover, elevating the small intestines out of the true pelvis paves the way for high dose (brachy)radiotherapy with less radiation enteritis. The technique of the pedicled omentoplasty is straightforward and takes 20-30 min extra operating time. We use pedicled omentoplasty for covering large operating fields instead of reperitonealization, to prevent radiation enteritis, as a matrix for grafting, to treat serious intraperitoneal infections and to facilitate hemostasis. Our experience of 48 omentoplasty procedures in gynecology is described. PMID- 7774746 TI - Effect of some sex steroid hormones on human spermatozoa migration in vitro. AB - The potential chemotactic effect of sex steroid hormones on human spermatozoa was studied. In an in vitro model, the number of human sperm cells migrating to Biggers-Whitten-Whittingham (BWW) medium containing progesterone in concentrations from 1 microgram/ml to 100 micrograms/ml was significantly higher than the number migrating to control medium (pure BWW). The presence of testosterone in the incubation medium decreases the migration of spermatozoa, and estradiol and estriol did not cause any visible changes in their behaviour. This effect of changes in migration was interpreted as chemotaxis of spermatozoa. PMID- 7774747 TI - The effect of labetalol on maternal haemodynamics and placental perfusion in awake near term guinea pigs. AB - The effect of labetalol (20 micrograms/kg/min) on maternal haemodynamics in general, and absolute placental perfusion in particular, was studied in eight chronically instrumented hypertensive guinea pigs near term. One day before drug testing, all experimental animals were subjected to haemoconcentration (haematocrit was gradually raised from 35.9 +/- 2.9 to 49.4 +/- 5.6 vol%, mean +/ S.D.) to establish a prolonged and stable state of hypertension. This procedure increased mean arterial pressure from 59.7 +/- 7.2 to 70.3 +/- 8.6 mmHg, and was paralleled by mild foreseeable systemic haemodynamic effects (redistribution of cardiac output away from intestines and brain), without consistent changes in the maternal placental blood flow. The hypotensive effect of labetalol was paralleled by a selective reduction in placental perfusion as reflected by a consistent fall in weight-specific cardiac output fraction (from 55.5 +/- 26.6 to 40.9 +/- 12.5%/100 g, P < 0.05) and blood flow (from 155 +/- 76 to 112 +/- 44 ml/min/100 g, P < 0.05) to the placentas. The concomitant placental resistance had increased consistently from 0.55 +/- 0.26 to 0.62 +/- 0.32 mmHg.min.100 g/ml, P < 0.05. We conclude that in awake late-pregnant hypertensive guinea pigs, labetalol reduces uteroplacental blood flow selectively. We speculate that the latter selective effect is secondary to the fall in blood pressure. PMID- 7774748 TI - Thoracic electrical bioimpedance: suitable for monitoring stroke volume during pregnancy? AB - To obtain normal values for maternal stroke volume and cardiac output during pregnancy, a non-invasive, accurate and reproducible method is required. The thoracic electrical bioimpedance (TEB) method may be suitable. However, this method is as yet only qualified for short-term trend recordings, since it assumes that body dimensions such as height, weight and thoracic circumference remain constant during the study. This may not be the case in long-term studies, especially during pregnancy. In this paper it is argued that changes in stroke volume (SV) during pregnancy are reflected most strongly when using the formula: SV = P VET (dZ/dt)max/Z0, where P is a personal factor to be determined at the beginning of pregnancy; VET the ventricular ejection time; (dZ/dt)max the maximum of the first derivative of the thoracic impedance during the cardiac cycle and Z0 the time average of this impedance during the cardiac cycle. Indexed parameters should not be used as this reduces sensitivity. Commercial equipment, based upon other algorithms, can be used by feeding the right parameters for each series of measurements. This enables calculation, trends in stroke volume and cardiac output for longitudinal studies for instance during pregnancy. PMID- 7774749 TI - Prolongation and improvement of prostasome promotive effect on sperm forward motility. AB - Prostasomes isolated from human seminal plasma stimulated the forward motility of buffer-washed, and therewith immobilised, normal human spermatozoa in a dose- and time-related fashion. Albumin exhibited a similar capacity for stimulation. Combining prostasomes with 5 mmol/l of any of the hexoses fructose, glucose or mannose (but not galactose) resulted in a prolongation and improvement of the effect by prostasomes (or albumin) for the first 150 min. Hence, a dose-response effect at 60 and 120 min was obtained by prostasomes on sperm forward motility provided 5 mmol/l of fructose was present--otherwise not. Many substances besides the hexoses were examined for possible positive effects on sperm forward motility in concert with prostasomes with no additional effect. Enrichment of optimum concentrations of prostasomes and glucose with 2 mmol/l of adenine stimulated further the velocity parameters of the spermatozoa over time. The effect of adenosine was less evident under these conditions. Experiments carried out with prostasomes in the presence of divalent cations or chelators suggested that magnesium ions are essential for sperm forward motility. There appeared to be a safety margin concerning calcium ions, and zinc ions did not seem to be primarily involved in sperm forward motility in the presence of prostasomes. PMID- 7774750 TI - Endometriosis of the sciatic nerve: case report demonstrating the value of MR imaging. AB - Among the many causes of sciatica, endometriosis, a rare aetiology, should be considered in menstruating women in view of the diagnostic strategy and ensuing therapeutic implications. We report a case of sciatic nerve involvement with endometriosis in contact with the nerve in the left sciatic notch. Exploration by MRI was invaluable for the diagnosis, revealing a signal on the stem of the nerve suggestive of a lesion with haemorrhagic content. PMID- 7774751 TI - Pre-rupture diagnosis and management of rudimentary horn pregnancy in the first trimester. AB - A case of pregnancy in the rudimentary horn of a unicornuate uterus, suspected on routine pelvic examination and confirmed by sonography as early as at 8 weeks of gestation is presented. Ultrasonographic findings of the case and surgical management of ipsilateral adnexa at the time of excision of rudimentary horn are discussed. PMID- 7774752 TI - A case of tracheal agenesis delivered of a patient with mosaic Turner's syndrome. AB - We describe a female infant with tracheal agenesis associated with severe complicated malformations including the cardiovascular system. The patient was born of a mother with mosaic Turner's syndrome at 35 weeks of gestation after premature rupture of the membranes during treatment for polyhydramnios. The patient died 2 days after birth and the autopsy disclosed tracheal agenesis and associated multiple anomalies. PMID- 7774753 TI - Absence of electrical uterine activity after endoscopic access for fetal surgery in the rhesus monkey. PMID- 7774754 TI - Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 1. Protective effect of Ginkgo biloba extract (EGb 761). AB - The antioxidant potential of Ginkgo biloba extract (EGb 761) on healthy human erythrocyte membranes was investigated. Lipoperoxidation was induced in erythrocyte suspensions using hydrogen peroxide, in the presence of EGb 761 at 37 degrees C; malondialdehyde production was determined as the indicator of lipoperoxidation during the incubation period. The results for EGb 761 at concentrations of 0, 25, 50, 125, 250 and 500 micrograms/ml suggest that the antioxidant potential of EGb 761 in erythrocyte membranes increases with dose. Similarly, using different incubation periods (0, 15, 30, 45 or 60 min) indicated that the antioxidant effect of EGb 761 increased by the incubation time. PMID- 7774755 TI - Effect of nadifloxacin on neutrophil functions. AB - Recent reports indicate that nadifloxacin is an effective therapy for acne vulgaris and has a mechanism of action similar to that of the tetracyclines which act directly as antioxidants against infiltrated neutrophils. The effects of nadifloxacin on neutrophil functions, including the generation of reactive oxygen species, chemotaxis and phagocytosis were investigated. Nadifloxacin reduced the numbers of superoxide radical anions (O2-) and hydroxyl radicals (OH.) generated by neutrophils. The drug did not, however, significantly inhibit neutrophil chemotaxis and phagocytosis nor did it decrease the levels generated in a cell free, xanthine-xanthine oxidase system. These results indicate that the clinical effectiveness of nadifloxacin may be partly due to its inhibitory action on the generation of O2- and OH. by neutrophils leading to a reduction in oxidative tissue injury. PMID- 7774756 TI - Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis. AB - The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid. PMID- 7774757 TI - Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases. AB - Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Federation Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective. PMID- 7774758 TI - Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes. AB - To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 +/- 2.2 for the chronic pancreatitis group and 2.4 +/- 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 +/- 3.6% and 10.1 +/- 3.3% (means +/- SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea. PMID- 7774759 TI - Evaluation of anti-HTLV-1 antibody in primary glomerulonephritis. AB - Human T-cell leukaemia virus type-1 (HTLV-1) is known to cause adult T-cell leukaemia. The prevalence of anti-HTLV-1 antibody in haemodialysis patients has been reported to be higher than that in the general population. The anti-HTLV-1 antibody-positive rate in patients with primary glomerulonephritis in the Nagasaki district, an endemic area of HTLV-1, was evaluated. The antibody positive rates in patients with primary glomerulonephritis (9.9%) and in haemodialysis patients (18.4%) were significantly higher than the rate in general blood donors (6.6%). Of 142 patients with primary glomerulonephritis, 14 (9.9%) were positive for the antibody; histological evaluation of these patients showed minor glomerular abnormality in one, mesangial proliferative glomerulonephritis in eight (IgA nephropathy in six and non-IgA nephropathy in two), membranous nephropathy in three, and crescentic glomerulonephritis in two. Evaluation of 10 antibody-positive patients by immunofluorescent microscopy showed immunocomplex type nephritis in nine, suggesting the involvement of HTLV-1-associated antigen in the development and progression of glomerulonephritis. PMID- 7774760 TI - Zolpidem in insomnia: a 3-year post-marketing surveillance study in Switzerland. AB - A multicentre post-marketing surveillance study was conducted in Switzerland in routine practice and involved 1972 insomniac patients treated with zolpidem, an imidazopyridine hypnotic agent. The patients were representative of the general insomniac population (65% women; mean age 55 years; 29% over 65). Of the patients, 87% were treated with a zolpidem dosage of 10 mg/day and the median treatment duration was 30 days. All adverse events were collected through spontaneous reporting. A total of 175 patients (8.9%) reported 343 adverse events, and 102 (5.2%) of them discontinued treatment. CNS (central nervous system)-related adverse events accounted for 66% of the total, the most common events being residual daytime sedation and insufficient efficacy in 3.7% and 1.6%, respectively; confusion, disorientation, nervousness, nightmares, amnesia, impaired concentration and anxiety were observed in a lower proportion. Gastro intestinal symptoms, headache and skin reactions were the most frequent non-CNS related effects. No serious adverse event was reported and no new risk factors or at-risk populations were identified. The safety profile of zolpidem is thus consistent with its known pharmacological properties, the results of previous clinical trials, and the cumulative international experience gained with this short-acting hypnotic drug. PMID- 7774761 TI - Friedreich's ataxia in the elderly. AB - Friedreich's ataxia is one of the best defined and most common forms of hereditary ataxia of unknown aetiology. It is transmitted in an autosomal recessive manner, appearing sporadically, usually in childhood or adolescence. The case of an elderly patient with a possible diagnosis of late-onset Friedreich's ataxia is reported; this is thought to be the only such case in the literature. The 91-year-old Anglo female presented with ataxia that had been progressive over the last 5 years. Magnetic resonance imaging scans of the head revealed mild peripheral cerebellar atrophy and moderate cerebral atrophy. The patient's parents were unaffected but two of her six siblings had had Friedreich's ataxia starting in childhood, and four of her grandfather's siblings had had an undiagnosed illness that left them in wheelchairs early in life. Friedreich's ataxia was diagnosed in view of the strong family history and non revealing magnetic resonance imaging of the brain. PMID- 7774763 TI - The neurophysiological evaluation of auditory discrimination. PMID- 7774762 TI - Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 2. Comparison of the antioxidant effect of Ginkgo biloba extract (EGb 761) with those of water-soluble and lipid-soluble antioxidants. AB - An in vitro model using healthy human erythrocyte suspensions was used to compare the antioxidant effect of standardized Ginkgo biloba extract (EGb 761) with those of water-soluble (ascorbic acid, glutathione and uric acid) and lipid-soluble (alpha-tocopherol and retinol acetate) antioxidants. Lipid peroxidation was induced by hydrogen peroxide in the absence (control) and presence of antioxidants at low (25 micrograms/ml) and high (250 micrograms/ml) concentrations. Malondialdehyde production was determined as the indicator of lipid peroxidation during the incubation period. The results suggest that all of the antioxidants, except ascorbic acid, have antioxidant potential in this system in a concentration-dependent manner. When the antioxidants were compared, EGb 761 was found to be more effective than water-soluble antioxidants, and as effective as lipid-soluble antioxidants. Among the lipid-soluble antioxidants there was no significant difference in potency between alpha-tocopherol and retinol acetate, but uric acid was the most potent of the water-soluble antioxidants. The antioxidant potency of EGb 761 appears to be comparable with that of the well known antioxidants alpha-tocopherol and retinol acetate. PMID- 7774764 TI - Developmental studies and clinical application of mismatch negativity: problems and prospects. AB - There is wide interest in the clinical application of mismatch negativity (MMN) to assess discriminative capabilities in individuals whose auditory capacities are difficult to determine, including infants, young children and those with severe cognitive impairment. Before MMN can be used as a clinical electrophysiologic measure, it is necessary to establish that it can be reliably elicited in normal individuals. This chapter describes a detailed analysis of MMN recorded in a group of healthy 8-yr-old children to assess intrasubject and intersubject reliability of the response. We conclude that although statistically reliable results can be obtained with group data, and perhaps even in individuals when large numbers of stimuli can be delivered, the unfavorable signal to noise ratio of individual MMN data currently limits its clinical applicability. Suggestions for approaches to surmount these difficulties are presented for its eventual clinical usefulness. PMID- 7774765 TI - Practical issues in the clinical application of mismatch negativity. AB - The mismatch negativity (MMN) recordings provide an objective measure of the preattentive, automatic auditory discrimination function. This article deals with issues central to the recording of the MMN and the interpretation of the results for clinical and electrodiagnostic purposes. The methods of acquiring as pure an MMN response as possible, i.e., one not contaminated by auditory cortical responses reflecting other functions, are discussed first. Second, other technical questions associated with the recording are reported on, e.g., what MMN parameters should be recorded and how, what is the smallest recordable MMN response, and what is the repeatability of the MMN recordings. Then, the effect of various physiological factors on the MMN (age, alertness, gender, topographic distribution of the MMN) is considered. The correlation between auditory discrimination performance and the MMN amplitude, observed in normal population, is dealt with. Finally, there is a short concluding overview on clinical findings of MMN recordings and discussion on their electrodiagnostic applications. PMID- 7774766 TI - The mismatch negativity in cochlear implant users. AB - For individuals with severe or profound hearing loss, electrical stimulation of surviving neural elements by a cochlear implant may partly restore a sensation of hearing. Determining the extent of restoration based on behavioral measures may be difficult, particularly when evaluating young children or individuals who have little or no experience with normal hearing. In normal-hearing individuals, an objective measure of sound discrimination may be obtained by studying the mismatch negativity (MMN) component of the auditory evoked potential. The MMN may be evoked by a number of physical differences in acoustic stimuli including duration and pitch. For cochlear implant users, analogous stimulus differences may be produced by changing the length of a stimulus pulse train or by changing the pair of activated electrodes along a multi-electrode implant array. This paper will provide an overview of our current results, comparing evoked response data recorded from both normal-hearing individuals and cochlear implant users. In both normal-hearing individuals and cochlear implant users, MMNs were evoked by differences in stimulus train duration and pitch (or electrode pair activation in cochlear implant users). These findings suggest that the MMN may be a useful method for assessing the discriminability of electrical stimulation patterns produced by a cochlear implant. Eventually, information gained by MMN testing may yield important information for developing rehabilitation programs for the individual user. PMID- 7774767 TI - Neurophysiologic bases of speech discrimination. AB - The mismatch negativity (MMN) is an automatic cortical evoked potential that signifies the brain's detection of acoustic change. In other words, the MMN reflects the neurophysiologic processes that underlie auditory discrimination. As such, the MMN provides an objective tool for evaluating central auditory mechanisms involved in speech perception. We are using the MMN to study the central auditory processes that encode acoustic changes important for speech perception in 1) normal-hearing adults and children, 2) individuals with impaired auditory systems (including persons with learning disabilities, attention deficit disorders, cochlear implants), and 3) an animal model. Specifically, we have demonstrated that the MMN provides information about the central processing of fine acoustic differences, the neuroanatomic pathways that encode acoustic change, central auditory processing in the presence of peripheral hearing deficits, and central auditory system plasticity. In addition, we have considered methodological challenges associated with measuring the MMN in individual subjects. Several methodological issues--including appropriate stimuli, stimulus presentation variables, the recording protocol and environment, and validation of the MMN in individuals--are discussed. PMID- 7774768 TI - Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. AB - Infrequent ("deviant") sounds occurring in a sequence of repetitive ("standard") sounds elicit an event-related brain potential (ERP) response called the mismatch negativity (MMN) even in the absence of attention to these sounds. MMN appears to be caused by a neuronal mismatch between the deviant auditory input and a sensory memory trace representing the standard stimuli. This automatic mismatch process has presumably a central role in discrimination of changes in the acoustic environment outside the focus of attention. Thus, localizing cerebral generators of MMN might help identify brain mechanisms of auditory sensory memory and involuntary attention. This review summarizes results from studies aimed at localizing MMN generators on the basis of (1) scalp-distribution, (2) magnetoencephalographic (MEG), (3) intracranial, and (4) brain-lesion data. These studies indicate that a major MMN source is located in the auditory cortex. However, the exact location of this MMN generator appears to depend on which feature of a sound is changed (e.g., frequency, intensity, or duration), as well as on the complexity of the sound (e.g., a simple tone versus complex sound). Consequently, memory traces for different acoustic features, as well as for sounds of different complexity, might be located in different regions of auditory cortex. However, MMN appears to have generators in other brain structures, too. There is some evidence for contribution of frontal-lobe activity to the MMN, which might be related to the involuntary switching of attention to a stimulus change occurring outside the focus of attention. In addition, intracranial MMN recordings in animals suggest that at least in some species, MMN subcomponents also may be generated in the thalamus and hippocampus. PMID- 7774769 TI - The mismatch negativity of event-related potentials as a probe of transient auditory memory: a review. AB - The use of the mismatch negativity as a probe to study the memory upon which it depends is reviewed. Topics about the memory include its duration, its capacity, the kind of information that can be stored in the memory, how the information is stored, whether the memory is accessed in parallel or in series, whether it is hard-wired or can be modified by experience, and its relationship to sensory memory. PMID- 7774770 TI - The mismatch negativity: a powerful tool for cognitive neuroscience. AB - This article reviews research on the relatively recently discovered event-related potential component, the mismatch negativity (MMN), which is of great potential interest for understanding central auditory function and various forms of its pathology. This change-specific response can serve as an accurate objective measure for central sound representations that form the basis, for instance, for correct hearing of speech. Deficiencies in the MMN may be related to different forms of deficits in central auditory processing. PMID- 7774771 TI - Event-related potentials and the categorical perception of speech sounds. AB - OBJECTIVE: To determine whether there are physiological correlates of categorical perception. DESIGN: Human evoked potentials were recorded in response to computer modified speech sounds from a nine-stimulus continuum between /ba/ and /da/. In the first experiment, subjects listened to trains composed of 52% /ba/ or /da/ and 6% of each of the other eight stimuli and classified the stimuli as "ba" or "da." In the second experiment, subjects read a book and ignored trains containing a standard stimulus (p = 80%) and two deviant speech sounds (p = 10% each), one within the same category as the standard and the other across the category-boundary. The third experiment was similar to the first except that the subject was reading. The fourth experiment compared the responses to stimuli that deviated from standards in terms of their phonemic category or intensity. RESULTS: An N2-P3 complex was evoked by those stimuli in the more improbable category when the stimuli were attended to in the first experiment. In the second and third experiments, there was a clear mismatch negativity (MMN) for the across category deviant stimuli when the standard stimulus came from the /ba/ end of the continuum. However, when the standard stimulus came from the /da/ end of the continuum, there was no definite MMN. The overall frequency-content of our /da/ stimulus was broader than that of the /ba/ stimulus. A deviant stimulus from the /da/ end of the continuum thus contained frequencies which were not present in the /ba/-standard stimuli and these frequencies could elicit a MMN. In the fourth experiment the MMN evoked by a small change in intensity was much larger than that evoked by a change in phonemic category. CONCLUSIONS: The N2-P3 complex accurately reflects the phonemic categorization of speech stimuli. The MMN evoked by changes in speech sounds may indicate the detection of acoustic rather than phonetic changes. PMID- 7774773 TI - There is a story to tell. PMID- 7774772 TI - On the origin and development of the mismatch negativity. AB - This review summarizes a number of findings related to the generation, development, and diagnostic value of mismatch negativity (MMN). The animal analogue of MMN to frequency contrast can be observed in the primary and secondary auditory cortical and also in the association cortical recordings. It is shown that subcortical sensory specific and archicortical structures may also contribute to the processes involved. The results are more complex than would be predicted by the notion that only the primary system plays an active role in the comparison processes reflected by the MMN that and the nonprimary pathway acts only as a modulating influence. The fundamental nature of the brain functions reflected by MMN is suggested by the demonstration of MMN in sleep and anesthesia, though in limited conditions. The postnatal development of automatic stimulus comparison, as indexed by MMN, presents an isochronicity, contrary to other evoked potential components whose development is not complete until puberty. Thus, the MMN provides a stable measure for electrophysiological assessment of auditory perception. This possible diagnostic value of the MMN is shown in studies of aphasics which emphasize the nature of perceptual deficits in the processing various speech and nonspeech stimuli. PMID- 7774774 TI - Medicaid free distribution programs and availability of childhood immunizations in rural practices. AB - BACKGROUND: The impact of a federal program that provides free childhood immunizations to private physicians for their Medicaid patients was examined. The aim of the study was to find out whether the program affected the availability of immunizations in rural and urban family physicians' practices. METHODS: A survey form about physician practice policies was sent to a stratified sample of 1,184 urban and rural family physicians in six states. States that participated in the federal free vaccine program were matched with states in the same region that did not participate in this program. RESULTS: States with no free vaccine distribution program showed a significant difference in the availability of immunizations from rural family physicians, compared with urban physicians (52% vs 87%, P < .001). However, in states with free distribution programs, no difference was found between rural and urban physicians (90% vs 94%, P = .18). In states without free distribution programs, immunization availability showed a positive and significant correlation with the size of the community where the physician practiced (Pearson correlation coefficient = .48, P < .001), whereas no correlation between community size and immunization availability existed in states with a free distribution program (Pearson correlation coefficient = .04, P = .53). CONCLUSION: Federal programs that offer free childhood immunizations to physicians for use in Medicaid populations have a dramatic effect on increasing immunization availability in rural areas. PMID- 7774775 TI - Predictors of first-contact care in a poor urban community. AB - OBJECTIVE: The aim of the study was to identify predictors of first-contact care in a population of poor urban residents. METHODS: Information from a community health needs survey was used for the study. The sample included adult residents in five urban census tracts with a large proportion of Puerto Rican Hispanics. Potential predictors included social characteristics, source of health insurance, perceived health status, number of chronic diseases, use of alternatives to medical care, smoking status, and problems with alcohol use. RESULTS: A total of 826 household interviews were completed for a participation rate of 78% among eligible households. Individuals with no health insurance were six times more likely to lack a source of first-contact care, compared with those who have traditional indemnity insurance. Those who only had Medicaid were four times more likely to lack a source of first-contact care. Respondents involved in Medicaid managed care programs had similar access to first-contact care as those with commercial insurance. Individuals who reported problems with alcohol were three times more likely to lack a source of first-contact care. CONCLUSIONS: Health insurance is an important predictor of access to first-contact care for poor urban residents. Those who identify problems with alcohol and African-Americans have additional difficulty with access to first-contact care. PMID- 7774776 TI - Depression in mothers of children with attention deficit hyperactivity disorder. AB - BACKGROUND AND OBJECTIVES: Does having a child with attention deficit hyperactivity disorder (ADHD) increase the risk of depression in the child's mother? The present study was initiated to explore this issue in a primary care setting and evaluate the need for routine screening of maternal depression in mothers of children with ADHD. METHODS: The subjects were 59 biological mothers of children with ADHD. All were patients in a rural, private, office-based family practice. Each subject was given a Zung Self-rating Depression Scale (SDS). After completion, the mothers were interviewed to confirm or exclude depression by Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria. RESULTS: Thirty-nine of the 59 mothers returned a completed Zung SDS. No statistically significant differences were noted between the respondents and nonrespondents, nor between ADHD children of respondents and nonrespondents. Twenty-one respondents had Zung scores in the depressive ranges. By DSM-III-R criteria, 15 were subsequently found to be depressed. None of the 18 mothers with normal scores on the Zung were found to be currently depressed. CONCLUSIONS: The incidence of major and minor depression in primary care outpatients is 4%-6% and 6%-14%, respectively. However, the present study reveals an incidence of 17.9% for major depression and 20.5% for minor depression in mothers of children with ADHD, suggesting that routine screening for maternal depression needs to be considered when children are diagnosed with ADHD in primary care settings. PMID- 7774777 TI - Family medicine research: a matter of values and vision. PMID- 7774778 TI - Differences in labor and delivery experience in family physician- and obstetrician-supervised teaching services. AB - BACKGROUND: Other studies have shown that family physicians' pregnancy management styles are different from obstetricians' styles. This study examines whether these differences also exist in teaching services supervised by family physicians and obstetricians. METHODS: A retrospective study was done of deliveries performed by residents at five teaching hospitals in five states. A total of 4,558 women were admitted to teaching services supervised by either family physicians (n = 1,754) or obstetricians (n = 2,804). Medical records for women whose labor and delivery were supervised by family physicians and obstetricians were reviewed and compared for demographics, pregnancy history, delivery management, and outcome variables. RESULTS: Women admitted to teaching services supervised by family physicians were more likely to be younger and have no insurance, compared with those on services supervised by obstetricians. Even after adjustment for pregnancy risk, obstetrician-supervised teaching services had an increased incidence of preterm labor, more frequent use of epidural anesthesia, and higher episiotomy and cesarean section rates than family practice teaching services. CONCLUSIONS: The demographic and clinical characteristics of family practice and obstetric teaching services differ. Patients on the services supervised by family physicians were more representative of the maternity practice of practicing family physicians. PMID- 7774779 TI - Factors associated with research productivity in family practice residencies. AB - BACKGROUND: Research productivity and the associated features of research productivity in family practice residencies have not been well described. The objectives of this study are to describe residency research productivity and identify the set of independent factors that best characterize programs at various levels of productivity. METHODS: A 23-item survey was mailed to 226 randomly selected family practice residency directors. The survey included items on program demographics, mentoring, resident and faculty research activities, and program research resources. Factor and discriminant analyses were performed to identify the major independent factors associated with productivity. RESULTS: A total of 154 completed surveys were received for a response rate of 68%. Based on a cross tabulation of grants per program and publications per faculty, 22% of programs had high productivity, 46% had medium productivity, and 32% had low productivity. The significant factors of mentor support, amount of research activity, and program size contributed independently to the classification of programs by relative level of research productivity. These associations remained significant when university programs were excluded. CONCLUSIONS: Family practice residencies with relatively higher research productivity are more likely to have three characteristics than lower productivity programs: availability of a research mentor, more faculty research activities, and larger program size. PMID- 7774780 TI - Economic viability of a model rural family practice. AB - BACKGROUND AND OBJECTIVES: A model rural clinic was established by the Quincy Family Practice Residency Program with the financial support of sponsoring local hospitals. The purpose of the study was 1) to determine the financial viability of such a model practice and 2) to determine the practice's financial effect on the sponsoring hospitals. METHODS: The rural practice was established in a medically underserved area 30 miles from the sponsoring hospitals. A cost analysis of months 7-18 of operation was performed, including an analysis of charges generated at the sponsoring hospitals. Theoretical models of practice to enhance economic viability were explored. RESULTS: The 3,051 office visits fell short of expectations. These visits generated a net practice income of $18,596. Had the practice sought full payment for these visits instead of accepting Medicare assignments, the net income potential would have been $39,182. Growth of the practice until it reached the average size of a typical rural family practice (6,000 annual visits) would produce a net income of $67,113 with Medicare assignments and $103,578 if Medicare assignments were not accepted. Had the practice been a federally designated rural health clinic, a mid-level practitioner with physician supervision could have generated a net practice income of $53,640 for 3,051 visits or $138,863 for 6,000 visits. Referrals from the model clinic for laboratory work, radiology, and hospital admissions generated $9.17 in charges for the sponsoring hospitals for each dollar charged by the clinic. CONCLUSIONS: The financial viability of rural practices is adversely affected by the Medicare reimbursement system. Our model clinic had a positive economic effect on the sponsoring hospitals, suggesting that innovative collaborative sponsorship of such clinics may be mutually beneficial. PMID- 7774781 TI - A randomized, controlled trial of the influence of prenatal parenting education on postpartum anxiety and marital adjustment. AB - OBJECTIVE: The aim of this study was to measure the impact of two middle trimester parenting communication classes on postpartum anxiety, marital adjustment, and postpartum adjustment. METHODS: Seventy primiparous, low-risk couples enrolled in prenatal classes in a large urban hospital were randomized to experimental and control groups. An educational intervention consisting of two second-trimester classes was facilitated by two social workers. The classes were based on a previous assessment of the educational needs of postpartum couples and contained didactic sessions, role-playing sessions, and values clarification exercises. The Spielberger State-Trait Anxiety Inventory and the Dyadic Adjustment Scale were administered to both groups prenatally in the second trimester and at 6 weeks and 6 months postpartum. A modified version of the O'Hara Postpartum Adjustment Questionnaire was administered at 6 weeks and 6 months postpartum. RESULTS: Both groups scored comparably in the prenatal period. The experimental group scored significantly lower on anxiety and higher on dyadic adjustment at both postpartum time periods than the control group. The experimental group also indicated a higher degree of postpartum adjustment. CONCLUSION: Prenatal parenting communication classes had a significant impact on postpartum anxiety, postpartum marital satisfaction, and postpartum adjustment. PMID- 7774782 TI - [Gastric schwannoma. Report of a case]. AB - Gastric schwannoma is a rare and benign neurogenic tumor. Diagnosis of this entity is uncertain previous to surgery, being this tumor localized in the sub mucosa. Final diagnosis is achieved by surgical removal and histological examination. PMID- 7774783 TI - [Splenic pseudocystic. Report of a case]. AB - Splenic pseudocysts represent 70 to 80% of the non parasitic cysts of this organ. Malaria, infectious mononucleosis, tuberculosis and t. pallidum infection are predisposing factors. Cystic characteristics are determined by CT-SCAN and ultrasound. Final diagnosis is achieved by hystological examination. This is a case report. PMID- 7774784 TI - [Abstracts of the XI Latin American Congress of Pediatric Gastroenterology and Nutrition, II Ibero Latin American Congress of Pediatric Gastroenterology and Nutrition, II Venezuelan Congress of Pediatric Gastroenterology]. PMID- 7774785 TI - [Bacterial microflora and intestinal ecosystem. Physiopathology of the contaminated small bowel. Acute diarrhea. Environment in Spain]. PMID- 7774786 TI - [Metabolic impact of acute diarrhea]. PMID- 7774787 TI - [Nutritional factors affecting diarrhea susceptibility]. PMID- 7774788 TI - [Economic significance of acute diarrhea]. PMID- 7774790 TI - [The management of medical care provided to hospitalized patients]. PMID- 7774789 TI - [What may be standardized about re-feeding in 1994?]. PMID- 7774792 TI - [Early gastric cancer staging by radiology, endoscopy, trans-endoscopic ultrasonography and its anatomo-pathological correlation]. AB - Early gastric cancer detection is still in its more elementary step in the western hemisphere, while in Japan gastric cancer is detected mainly in its early stage. The aim of this article is to analyze the Japanese method for early gastric cancer detection and staging, by sketch of certain morphologic criterions and a report of a typical case. In our case the lesion's staging was predicted as submucosal by means of endoscopy and double contrast roentgenography. Endoscopic ultrasonography complemented the analysis. The standard anatomopathological work up for early gastric cancer in Japan is also analysed. By this former method the accuracy of the initial staging by endoscopy, and radiologic means was ensured. By a correct early gastric cancer diagnosis and staging a better selection of the surgical strategy and survival can be achieved. PMID- 7774791 TI - [Gastric leiomyoblastoma. Histomorphologic and immunologic analysis of 3 cases]. AB - We present three cases of Leiomioblastomas of stomach, diagnosed at the unit of Pathology of the Gastrointestinal Cancer Center "Dr Luis E. Anderson" -San Cristobal-Tachira State Venezuela. The lesions are analyzed from the clinical, morphological and immunohistological points of view, utilizing Queratine and Vimentin techniques. This neoplasm is not frequent but it is interesting because its biologic behavior not always correspond to its histology-pattern. PMID- 7774793 TI - BamHI and HindIII repetitive DNA families in the rice genome. AB - In this paper we describe a novel method of cloning representative members of different repetitive DNA families based on the screening of a rice (Oryza sativa) genomic library using DNA from different C0t fractions as probes. Two genomic clones, which represent two different repetitive DNA families in rice, were isolated by this method and have been characterized. Their nucleotide sequences, copy numbers, distributions in major rice genome types, methylation patterns, and chromosomal localizations were determined. PMID- 7774794 TI - Detection of genetic diversity in tea (Camellia sinensis) using RAPD markers. AB - Camellia sinensis is a beverage tree crop native to Southeast Asia and introductions have been made into several nonindigenous countries. No systematic assessment of genetic variability in tea has been done anywhere. In this study, random amplified polymorphic DNA (RAPD) analysis was used to estimate genetic diversity and taxonomic relationships in 38 clones belonging to the three tea varieties, assamica, sinensis, and assamica ssp. lasiocalyx. Extensive genetic variability was detected between species, which was partitioned into between and within population components. Seventy percent of the variation was detected within populations. Analyses based on band sharing separated the three populations in a manner consistent with both the present taxonomy of tea and with the known pedigrees of some clones. RAPD analysis also discriminated all of the 38 commercial clones, even those which cannot be distinguished on the basis of morphological and phenotypic traits. PMID- 7774795 TI - Phylogenetic relationships of the monogenomic species of the wheat tribe, Triticeae (Poaceae), inferred from nuclear rDNA (internal transcribed spacer) sequences. AB - Phylogenetic relationships of 30 diploid species of Triticeae (Poaceae) representing 19 genomes were estimated from the sequences of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. The ITS sequence phylogeny indicated that: (i) each genome group of species is monophyletic, concordant with cytogenetic evidence; (ii) Hordeum (I) and Critesion (H) are basal; (iii) Australopyrum (W) is closely related to Agropyron (P); (iv) Peridictyon (G), Heteranthelium (Q), and Dasypyrum (V) are closely related to Pseudoroegneria (S); (v) most of the annuals, Triticum s.l. (A, B, D), Crithopsis (K), Taeniatherum (T), Eremopyrum (F), Henrardia (O), Secale (R), and two perennials, Thinopyrum (J) and Lophopyrum (E), all of Mediterranean origin, are a monophyletic group. However, phylogenetic trees based on morphology group these Mediteranean species with various perennial lineages of the Arctic-temperate region. The molecular data and biogeography of the tribe suggest that the Mediterranean lineage is derived from the Arctic-temperate lineage and that the two lineages have evolved in parallel. Extensive morphological parallelism apparently obscures the true genealogical history of the tribe when only morphology is considered. PMID- 7774796 TI - A survey of DNA polymorphism within the genus Capsicum and the fingerprinting of pepper cultivars. AB - Interspecific genetic variation was examined in the genus Capsicum based on shared restriction fragments in Southern analyses. Four distinct clusters were delineated among 21 accessions of cultivated and wild pepper (C. annuum, C. baccatum, C. chacoense, C. chinense, and C. frutescens). Three tight clusters comprised of accessions belonging to C. annuum, C. frutescens, and C. baccatum, respectively, were formed, along with a fourth cluster comprised of one accession each of C. chinense and C. chacoense. All accessions were differentiated by this technique, and the clusters corresponded closely to previous morphology-based classification. Sufficient DNA polymorphism exists among these accessions that segregating populations useful for restriction fragment length polymorphism (RFLP) mapping could be constructed using any two pepper accessions as parents. Regression analysis indicates that genetic distance is a good predictor (R2 = 0.872) of the level of mappable DNA polymorphism in Capsicum. Intraspecific variability was examined among four C. annuum cultivars (NuMex R Naky, Jupiter, Perennial, and Criollo de Morelos 334) using both RFLPs and randomly amplified polymorphic DNA (RAPDs), allowing a comparative evaluation of the two techniques. Seventeen percent of the clones used singly in RFLP analyses were sufficient for the differentiation of these varieties, as were 12.5% of the RAPD PCR amplifications. Dendrograms constructed from RFLP and RAPD analyses of the intraspecific data are similar but not identical. Southern analysis and RAPD PCR should be useful for DNA fingerprinting and the discrimination of closely related C. annuum genotypes. PMID- 7774797 TI - Evolution of finger millet: evidence from random amplified polymorphic DNA. AB - Finger millet (Eleusine coracana ssp. coracana) is an annual tetraploid member of a predominantly African genus. The crop is believed to have been domesticated from the tetraploid E. coracana ssp. africana. Cytogenetic and isozyme data point to the allopolyploid nature of the species and molecular information has shown E. indica to be one of the genomic donors. A recent isozyme study questioned the proposed phylogenetic relationship between finger millet and its direct ancestor subspecies africana. An approach using random amplified polymorphic DNA (RAPD) was employed in this study to examine genetic diversity and to evaluate hypotheses concerning the evolution of domesticated and wild annual species of Eleusine. Unlike previous molecular approaches, the RAPD study revealed genetic diversity in the crop. The pattern of genetic variation was loosely correlated to geographic distribution. The allotetraploid nature of the crop was confirmed and molecular markers that can possibly identify the other genomic donor were proposed. Genotypes of subspecies africana did not group closely with those of the crop but showed higher affinities to E. indica, reflecting the pattern of similarity revealed by the isozyme study. The multiple origin of subspecies africana could explain the discrepancy between the isozyme-RAPD evidence and previous information. The RAPD study showed the close genetic affinity of E. tristachya to the E. coracana--E. indica group and understood the distinctness of E. multiflora. PMID- 7774798 TI - A transcript family from a long-range repeat cluster of the house mouse. AB - A family of closely related genes is a component of the polymorphic long-range repeat cluster D1Lub1 of the house mouse. Members of the gene family have diverged from one another by rearrangements and point mutations. D1Lub1 cluster have low (approximately 50) or high (> or = 500) copy numbers. In mice with high copy clusters five or six poly(A)+ RNAs are found, while in mice with low-copy clusters only a single member of the RNA family is detected. The RNA family is synthesized in a tissue-independent manner. Each member of the RNA family is defined by a set of DNA probes. Cross hybridization with the probes reveals common 5' regions and variable remaining parts. The RNA variants are probably transcribed from different gene copies. PMID- 7774799 TI - Amplification of Ac in tomato is correlated with high Ac transposition activity. AB - We have assayed the transposition activity of the maize transposable element Ac in transgenic tomato plants that had a single copy of Ac. We found that Ac elements were in either a high or low activity state and that an Ac insertion could cycle from low to high activity within a generation. The different transposition activities were not simply due to the chromosomal position of the element, because the same Ac insertion had different levels of activity in sibling plants. Transposition activity was measured by two methods, one genetic and one physical; both assays gave similar results for each plant studied. Notably, plants with active Ac elements had progeny with amplified Ac copy number, while no amplification was detected in lines containing Ac in a low activity state. Analysis of lines with amplified elements revealed that the elements could be either clustered or dispersed. Our results were consistent with amplification being the result of transposition. PMID- 7774800 TI - Molecular analysis of evolutionary patterns in U genome wild wheats. AB - The theory of pivotal-differential evolution states that one genome of polyploid wheats remains stable (i.e., pivotal) during evolution, while the other genome or genomes may become modified (i.e., differential). A proposed mechanism for apparent modification of the differential genome is that different polyploid species with only one genome in common may exchange genetic material. In this study, we analyzed a set of sympatric and allopatric accessions of tetraploid wheats with the genomic constitutions UM and UC. The U genome of these species is from Triticum umbellulatum and is considered to be the pivotal genome. The M and C genomes, from T. comosum and T. dichasians, respectively, are considered to be the differential genomes. Low copy DNA was analyzed using "sequence tagged site" primer sets in the polymerase chain reaction, followed by digestion with restriction enzymes. Genetic similarity matrices based on shared restriction fragments showed that sympatric accessions of different U genome tetraploid species did not tend to share more restriction fragments than did allopatric accessions. Thus, no evidence for introgression was found. Analysis of the diploid progenitor species showed that the U genome was less variable than the M and C genomes. Additionally, comparison of diploid and polyploid species using genome-specific primer sets suggests a possible polyphyletic origin for T. triunciale and T. machrochaetum. Thus, our results suggest that the differential nature of the M and C genomes may be the result of variability introduced by the diploid progenitors and not the result of frequent introgression events after formation of the polyploid. PMID- 7774801 TI - Molecular cloning of a bovine ornithine decarboxylase cDNA and its use in the detection of restriction fragment length polymorphisms in Holsteins. AB - A cDNA coding for ornithine decarboxylase (ODC) was isolated from a bovine liver cDNA library. The clone (1758 base pairs) consisted of 5'- and 3'-untranslated regions of 185 and 187 nucleotides, respectively, and an open reading frame of 1383 nucleotides encoding an ODC protein (M(r) 51,342 daltons) of 461 amino acids. Comparison of the nucleotide and the predicted amino acid of the cDNA with other mammalian ODCs showed a very high degree of homology both at the DNA and protein levels. The bovine ODC mRNA was identified by northern blot to be a single species with a molecular size of 2.35 kilobase pairs. Primer extension analysis indicated that the 5'-untranslated region of the bovine ODC mRNA was 312 nucleotides long. Southern blot analysis of bovine genomic DNA revealed restriction fragment length polymorphisms when cleaved with restriction enzymes PstI, MspI, TaqI, and Bg/I. PMID- 7774802 TI - An evaluation of sequence tagged microsatellite site markers for genetic analysis within Citrus and related species. AB - Microsatellites, also called sequence tagged microsatellite sites (STMSs), have become important markers for genome analysis but are currently little studied in plants. To assess the value of STMSs for analysis within the Citrus plant species, two example STMSs were isolated from an intergeneric cross between rangpur lime (Citrus x limonia Osbeck) and trifoliate orange (Poncirus trifoliata (L.) Raf.). Unique flanking primers were constructed for polymerase chain reaction amplification both within the test cross and across a broad range of citrus and related species. Both loci showed length variation between test cross parents with alleles segregating in a Mendelian fashion to progeny. Amplification across species showed the STMS flanking primers to be conserved in every genome tested. The traits of polymorphism, inheritance, and conservation across species mean that STMS markers are ideal for genome mapping within Citrus, which contains high levels of genetic variability. PMID- 7774803 TI - Analysis of annual Medicago species using RAPD markers. AB - Annual species of the genus Medicago have attracted interest as green manure and temporary forage crops. This study was conducted to determine if randomly amplified polymorphic DNA (RAPD) markers could be used to assess the variability within and among species. Several accessions of each six species (M. scutellata Mill., M. disciformis DC., M. murex Willd., M. truncatula Gaertn., M. polymorpha L., and M. rugosa Desr.) were studied. A phylogeny reconstructed with the computer program Phylogenetic Analysis Using Parsimony (PAUP) showed the same relationships as traditional taxonomy. Variation was present among accessions of all species. Several accessions were considerably different from others within the species (one of each M. scutellata and M. polymorpha) and four accessions of M. murex were differentiated by both morphology and RAPD banding patterns from the other accessions. These accessions may be useful to include in a core collection. Variation within accessions was present. Although the species are autogamous, the original seed collections may have been made from a number of plants in the same area. Also, some outcrossing or seed mixing may have occurred. Finally, at least 10 RAPD primers appear to be necessary in order to develop reliable estimates of relatedness among annual Medicago accessions. PMID- 7774804 TI - DNA-strand breaks in chromosomes of early mouse embryos as detected by in situ nick translation and gap filling. AB - The nick translation and gap filling procedures, without external addition of nicking enzymes, were performed in situ on fixed chromosomes of mouse preimplantation and postimplantation embryos and of bone marrow in order to detect possible DNA single-strand breaks (nicks and (or) gaps). All chromosome preparations were made using the same technique. Nick translation of chromosomal DNA with DNA polymerase I (Pol I) or gap filling with the Klenow fragment of Pol I in the presence of biotinylated-dUTP, demonstrated a regular absence of label on chromosomes of postimplantation embryos and bone marrow. No difference in sensitivity was found between the holoenzyme and the Klenow fragment. In preimplantation embryos, the chromosome reactivity in nick translation was highest at the blastocyst stage and varied according to cleavage divisions of the zygote. PMID- 7774805 TI - Association of RAPD marker with linolenic acid concentration in the seed oil of rapeseed (Brassica napus L.). AB - The F2 progeny (64 individuals) from the cross between oilseed rape (Brassica napus L.) cultivar Topas and R4 (a low linolenic mutation line) was analyzed with 8 RFLPs and 34 RAPDs to discover a genetic tag for gene(s) affecting linolenic acid concentration. According to variance analysis (ANOVA), one RAPD marker (25a) was significantly associated with linolenic acid content; the linolenic acid concentration in the seeds of F2 individuals showing the marker (includes both homo- and hetero-zygotes) was 7.43 +/- 1.35% and in those lacking the marker was 5.70 +/- 1.52%. Marker 25a may be used to facilitate selection for fatty acid composition in future breeding programs of oilseed rape. PMID- 7774806 TI - Detection of rye chromosome 2R using the polymerase chain reaction and sequence specific DNA primers. PMID- 7774807 TI - Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. AB - The insulin gene is one of the best paradigms of tissue-specific gene expression. It is developmentally regulated and is expressed exclusively in the pancreatic beta-cell. This restricted expression is directed by a tissue-specific enhancer, within the promoter, which contains an E-box sequence. The insulin E-box binds an islet-specific protein complex, termed 3a1. E-boxes bind proteins belonging to the basic helix-loop-helix (bHLH) family of transcription factors. The bHLH proteins function as potent transcriptional activators of tissue-specific genes by forming heterodimers between ubiquitous and cell-restricted family members. In addition, the cell-restricted bHLH members play an important role in specifying cell fate. To isolate the tissue-specific bHLH factor controlling insulin gene expression and study its role in islet cell differentiation, a modified yeast two hybrid system was utilized to clone a novel bHLH factor, BETA2 (beta-cell E-box trans-activator 2), from a hamster insulin tumor (HIT) cell cDNA library. Northern analysis demonstrates that high-level expression of the BETA2 gene is restricted to pancreatic alpha- and beta-cell lines. As expected of tissue specific bHLH members, BETA2 binds to the insulin E-box sequence with high affinity as a heterodimer with the ubiquitous bHLH factor E47. More importantly, antibody supershift experiments clearly show that BETA2 is a component of the native insulin E-box-binding complex. Transient transfection assays demonstrate that the BETA2/E47 heterodimer synergistically interacts with a neighboring beta cell-specific complex to activate an insulin enhancer. In contrast, other bHLH factors such as MyoD and E47, which can bind to the insulin E-box with high affinity, fail to do so. Thus, a unique, cooperative interaction is the basis by which the insulin E-box enhancer discriminates between various bHLH factors to achieve tissue-specific activation of the insulin gene. PMID- 7774808 TI - Association of an activator with an RNA polymerase II holoenzyme. AB - RNA polymerase II holoenzymes have been described that consist of RNA polymerase II, a subset of general transcription factors, and four SRB proteins. The SRB proteins, which were identified through a selection for genes involved in transcription initiation by RNA polymerase II in vivo, are a hallmark of the holoenzyme. We report here the isolation and characterization of additional SRB genes. We show that the products of all nine SRB genes identified thus far are components of the RNA polymerase II holoenzyme and are associated with a holoenzyme subcomplex termed the mediator of activation. The holoenzyme is capable of responding to a transcriptional activator, suggesting a model in which activators function, in part, through direct interactions with the holoenzyme. Immunoprecipitation experiments with anti-SRB5 antibodies demonstrate that the acidic activating domain of VP16 specifically binds to the holoenzyme. Furthermore, the holoenzyme and the mediator subcomplex bind to a VP16 affinity column. These results provide a more complete description of the RNA polymerase II holoenzyme and suggest that this form of the transcription apparatus can be recruited to promoters via direct interactions with activators. PMID- 7774809 TI - The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication. AB - The role of the origin recognition complex (ORC) was investigated in replication initiation and in silencing. Temperature-sensitive mutations in ORC genes caused defects in replication initiation at chromosomal origins of replication, as measured by two-dimensional (2-D) origin-mapping gels, fork migration analysis, and plasmid replication studies. These data were consistent with ORC functioning as a eukaryotic replication initiator. Some origins displayed greater replication initiation deficiencies in orc mutants than did others, revealing functional differences between origins. Alleles of ORC5 were isolated that were defective for silencing but not replication, indicating that ORC's role in silencing could be separated from its role in replication. In temperature-sensitive orc mutants arrested in mitosis, temperature-shift experiments caused a loss of silencing, indicating both that ORC had functions outside of the S phase of the cell cycle and that ORC was required for the maintenance of the silenced state. PMID- 7774810 TI - Localization of RecA-like recombination proteins on chromosomes of the lily at various meiotic stages. AB - The Rad51 and Lim15 proteins of lily, which are homologs of the bacterial RecA protein, were found on chromosomes in various stages of meiotic prophase 1. The presence of both Rad51 and Lim15 proteins as discrete foci on leptotene and zygotene chromosomes and their colocalization suggest that meiotic recombination begins at the leptotene stage with the cooperation of these proteins and continues in zygotene. Localization of the foci on or adjacent to the chromosomes suggests that these proteins bind to the chromatin loops that extend from the axial cores. The proteins in these foci may participate in the searching and pairing of homologous DNA sequences, as the RecA protein does. The different pattern of localization of the Rad51 protein between the leptotene and pachytene stages and the absence of the Lim15 protein in the pachytene stage suggest that the Rad51 protein plays different roles in these stages. PMID- 7774811 TI - p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. AB - Expression of p21 has been shown to be up-regulated by the p53 tumor suppressor gene in vitro in response to DNA-damaging agents. However, p21 expression can be regulated independently of p53, and here we show that expression of p21 in various tissues during development and in the adult mouse occurs in the absence of p53 function. However, most tissues tested did require p53 for p21 induction following exposure of the whole animal to gamma irradiation. These results show that normal tissue expression of p21 to high levels is not dependent on p53 and confirm that induction of p21 by DNA-damaging agents does require p53. p21 is expressed upon differentiation of p53-deficient murine erythroleukemia (MEL) cells, and the kinetics of induction of p21 in this system suggest that it may be involved in the growth arrest that precedes terminal differentiation. The gene is up-regulated in mouse fibroblasts in response to serum restimulation but the kinetics and levels of induction differ between wild-type and mutant cells. Expression of p21 message following serum restimulation is superinducible by cycloheximide in wild-type but not in p53-deficient cells. The increases in p21 mRNA are reflected in changes in p21 protein levels. p21 expression also appears to be regulated at the post-transcriptional level because moderate increases in mRNA expression, during differentiation of MEL cells and upon serum restimulation of fibroblasts, are followed by large increases in protein levels. Regulation of the mouse p21 promoter by p53 depends on two critical p53-binding sites located 1.95 and 2.85 kb upstream from the transcriptional initiation site. The sequences mediating serum responsiveness of the promoter map to a region containing the proximal p53 site. p53 appears to play a critical role in p21 induction following DNA damage. Moreover, p21 can be regulated independently of p53 in several situations including during normal tissue development, following serum stimulation, and during cellular differentiation. PMID- 7774812 TI - Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice. AB - Transforming growth factor-beta 1 (TGF-beta 1) is a modulator of cellular proliferation, differentiation, and extracellular matrix deposition. It is a potent epithelial growth inhibitor and can alter the differentiative properties of keratinocytes, in vitro, but little is known about its normal physiological function in the epidermis in vivo. Transgenic mice were generated using a keratin 10 (K10) gene promoter to drive constitutive expression of TGF-beta 1 in the suprabasal keratinocyte compartment. Surprisingly, these mice showed a two- to threefold increase in epidermal DNA labeling index over control mice, in the absence of hyperplasia. The transgene, however, acted in the expected fashion, as a negative regulator of cell growth, when hyperplasia was induced by treatment by 12-tetradecanoyl-phorbol-13-acetate (TPA). Epidermal TGF-beta type I and II receptor (T beta RI and T beta RII) levels were examined in control and transgenic mice during induction of hyperplasia by TPA. Whereas T beta RI levels remained relatively constant, T beta RII expression was strongly induced in TPA treated skins, prior to the induction of the growth inhibitory response to TGF beta 1, and its level of expression correlated with growth sensitivity to TGF beta 1 in vivo and in vitro. These results suggest that TGF-beta 1 and its type II receptor are part of the endogenous homeostatic regulatory machinery of the epidermis. PMID- 7774813 TI - The bli-4 locus of Caenorhabditis elegans encodes structurally distinct kex2/subtilisin-like endoproteases essential for early development and adult morphology. AB - Many secreted proteins are excised from inactive proproteins by cleavage at pairs of basic residues. Recent studies have identified several serine endoproteases that catalyze this cleavage in the secretory pathways of yeast and metazoans. These enzymes belong to the kex2/subtilisin-like family of proprotein convertases. In this paper we describe the molecular characterization of the bli 4 gene from Caenorhabditis elegans, which was shown previously by genetic analysis of lethal mutants to be essential for the normal development of this organism. Sequencing of cDNA and genomic clones has revealed that bli-4 encodes gene products related to the kex2/subtilisin-like family of proprotein convertases. Analysis of bli-4 cDNAs has predicted four protein products, which we have designated blisterases A, B, C, and D. These protein products share a common amino terminus, but differ at the carboxyl termini, and are most likely produced from alternatively spliced transcripts. We have determined the molecular lesions for three bli-4 alleles (h199, h1010, and q508) that result in developmental arrest during late embryogenesis. In each case, the molecular lesions are within exons common to all of the BLI-4 isoforms. The original defining allele of bli-4, e937, is completely viable yet exhibits blistering of the adult cuticle. Molecular analysis of this allele revealed a deletion that removes exon 13, which is unique to blisterase A. No RNA transcript corresponding to exon 13 is detectable in the blistered mutants. These findings suggest that blisterase A is required for the normal function of the adult cuticle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774814 TI - Myxococcus xanthus, a gram-negative bacterium, contains a transmembrane protein serine/threonine kinase that blocks the secretion of beta-lactamase by phosphorylation. AB - A gene, pkn2, encoding a Myxococcus xanthus protein with significant similarities to eukaryotic protein serine/threonine kinases, was cloned using the polymerase chain reaction. The open reading frame for the protein, beginning with a GUG initiation codon, consists of 830 amino acids. The amino-terminal 279 residues show 37% identity to catalytic domain of Pkn1, another protein serine/threonine kinase expressed during the development at the onset of sporulation. The catalytic domain of Pkn2 contains 27% and 25% identity to rat Ca2+/calmodulin dependent protein kinase and Bos taurus rhodopsin kinase, respectively. In the middle of the carboxy-terminal regulatory domain, there is a typical transmembrane domain consisting of 18 hydrophobic residues. The gene product, Pkn2, produced in Escherichia coli under a T7 promoter was phosphorylated at both serine and threonine residues. TEM-beta-lactamase produced in E. coli was found to serve as an effective substrate for Pkn2, phosphorylated only at threonine residues, shifting its apparent molecular mass from 29 to 44 kD. The phosphorylated beta-lactamase was unable to be secreted into the periplasmic space and localized in the cytoplasmic and membrane fractions. Analysis of phoA fusions with pkn2 demonstrated that Pkn2 is a transmembrane protein with the kinase domain in the cytoplasm and the 207-residue carboxy-terminal domain outside the cytoplasmic membrane. Disruption of pkn2 showed no effect on vegetative growth but reduced the yield of myxospores by 30%-50%. On the basis of the present results, we propose that Pkn2 is a transmembrane protein serine/threonine kinase that regulates the activity of endogenous beta-lactamase or related enzymes in response to an external signal yet to be identified. PMID- 7774815 TI - A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. AB - Stat1 and Stat3 are two members of the ligand-activated transcription factor family that serve the dual functions of signal transducers and activators of transcription. Whereas the two proteins select very similar (not identical) optimum binding sites from random oligonucleotides, differences in their binding affinity were readily apparent with natural STAT-binding sites. To take advantage of these different affinities, chimeric Stat1:Stat3 molecules were used to locate the amino acids that could discriminate a general binding site from a specific binding site. The amino acids between residues approximately 400 and approximately 500 of these approximately 750-amino-acid-long proteins determine the DNA-binding site specificity. Mutations within this region result in Stat proteins that are activated normally by tyrosine phosphorylation and that dimerize but have greatly reduced DNA-binding affinities. PMID- 7774817 TI - Quality of life: what is it? PMID- 7774816 TI - Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1 induced DNA bending and multiple protein-protein interactions. AB - In this study we examine the molecular basis for the synergistic regulation of the minimal TCR alpha enhancer by multiple proteins. We find that reconstitution of TCR alpha enhancer function in nonlymphoid cells requires expression of the lymphoid-specific proteins LEF-1, Ets-1 and PEBP2 alpha (CBF alpha), and a specific arrangement of their binding sites in the enhancer. We show that Ets-1 cooperates with PEBP2 alpha to bind adjacent sites at one end of the enhancer, forming a ternary complex that is unstable by itself. Stable occupancy of the Ets 1- and PEBP2 alpha-binding sites in a DNase I protection assay was found to depend on both a specific helical phasing relationship with a nonadjacent ATF/CREB-binding site at the other end of the enhancer and on LEF-1. The HMG domain of LEF-1 was found previously to bend the DNA helix in the center of the TCR alpha enhancer. We now show that the HMG domain of the distantly related SRY protein, which also bends DNA, can partially replace LEF-1 in stimulating enhancer function in transfection assays. Taken together with the observation that Ets-1 and members of the ATF/CREB family have the potential to associate in vitro, these data suggest that LEF-1 can coordinate the assembly of a specific higher-order enhancer complex by facilitating interactions between proteins bound at nonadjacent sites. PMID- 7774819 TI - Efficacy of hand massage in decreasing agitation behaviors associated with care activities in persons with dementia. PMID- 7774818 TI - Forgetfulness in elders: strategies for protective caregiving. AB - Nurses working with elders know from experience that an elder being viewed as forgetful negatively affects both the quality and the quantity of elders' social relationships. Avoiding stigmatization, in the presence of increased forgetting, presents a challenge for elders and their caregivers. Gerontologic nurses can assist forgetful elders with their personal impression management. They can protect these elders from being labeled by their social group. However, in order to assist elders in maintaining acceptable social impressions, nurses need to understand the impression management process and effective strategies for assisting forgetful elders in social situations. PMID- 7774821 TI - The caregiver needs a day off. PMID- 7774820 TI - A hospital-based skilled nursing facility: a special place to care for the elderly. PMID- 7774822 TI - Untying the elderly: response to quality-of-life issues. PMID- 7774823 TI - Extracts from Gerry's journal. PMID- 7774824 TI - Music as a nursing intervention for residents with Alzheimer's disease in long term care. PMID- 7774825 TI - Managing the cardiac arrest in the long-term care and subacute medical facility. PMID- 7774826 TI - Quality-of-life issues in home care. AB - Quality-of-life issues in home care are complex. Nurses not only must help the family consider these factors for the patient at home, but also they must examine the effects of home care on the primary caregiver and the entire family. Nurses use a holistic view in assessment to diagnose the needs of the client and the caregiver. Physiologic, psychologic, cultural, spiritual, and sociologic aspects are all considered. Nurses have an important role in assisting clients and their families to maximize the benefits of home care. They can help them with the provision of care in the current situation and to plan for the future for appropriate levels of care as the client's condition changes. These actions will result in an optimum quality of life for the client and the client's family. PMID- 7774827 TI - Maximizing calcium intake. PMID- 7774828 TI - Medications and sexual functioning in older adults. PMID- 7774829 TI - High-dose chemotherapy with autologous bone marrow support in ovarian carcinoma: the bottom line, more or less. PMID- 7774830 TI - A phase II trial of high-dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome. AB - Despite high initial response rates to platinum-based chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in the hematologic malignancies and lymphomas with high-dose therapy and bone marrow transplantation (BMT) when used early, suggesting that this therapy may also be of value in ovarian carcinoma. As a prelude to the use of high-dose chemotherapy with BMT early in the management of advanced ovarian carcinoma, we evaluated a new high-dose regimen in patients with relapsed/refractory ovarian carcinoma to define toxicities and responses. Thirty patients were treated, of whom 20 were platinum resistant and 22 had > 1 cm maximum diameter disease. They received mitoxantrone (75 mg/m2), carboplatin (1500 mg/m2), and cyclophosphamide (120 mg/kg), followed by an autologous BMT. Overall, 89% responded, with clinical complete responses seen in 88 vs 47% (P = 0.06) of platinum-sensitive vs -resistant disease. There was only one early death (3.3%) due to Aspergillus pneumonia. Median survival for all 30 patients was 29 months, and at 3 years 23% are alive without disease. There was a 10.1- vs 5.1 month progression-free survival for patients with platinum-sensitive versus resistant disease, and at a median follow-up of 12 months, 80% of the platinum sensitive patients are alive. This regimen is safe, and for platinum-sensitive disease appears superior to other salvage therapies. Its use should be explored earlier in the management of advanced ovarian carcinoma. PMID- 7774831 TI - Potential of cervical electrosurgical excision procedure for diagnosis and treatment of cervical intraepithelial neoplasia. AB - The aim of this study was to evaluate the diagnostic potential, treatment efficacy, specimen adequacy, and acute complication rate associated with electrosurgical excision procedure (EEP) of the cervix for the management of cervical intraepithelial neoplasia (CIN). Analysis was performed retrospectively on 153 consecutive patients who underwent EEP under colposcopic guidance. Patients with negative endocervical curettage (ECC), adequate colposcopy, and biopsy-proven CIN were considered candidates for therapeutic EEP, whereas patients with a positive ECC, inadequate colposcopy, or cytology two or more grades discordant from the biopsy results underwent diagnostic EEP. Histopathologic specimens were graded as adequate, suboptimal, or inadequate. Diagnostic EEP was performed in 85 cases, and the remaining 68 procedures were performed primarily for treatment. Specimens were graded as adequate in 83%, suboptimal in 13%, and inadequate in 4% of the diagnostic EEP's. Specimen adequacy correlated most strongly with operator experience (P < 0.05). Four patients were found to have microinvasive or invasive cervical carcinoma. Complications occurred in 7% of the EEPs performed. Most consisted of immediate or delayed hemorrhage. In conclusion, EEP is a safe, well-tolerated procedure which is acceptable as both a therapeutic and diagnostic tool in the management of CIN when performed by an experienced operator. We recommend that initial EEP procedures should be performed for therapeutic indications, since adequacy of EEP specimens correlated with the level of operator experience. PMID- 7774833 TI - Overexpression of the protein tyrosine phosphatase, nonreceptor type 6 (PTPN6), in human epithelial ovarian cancer. AB - Our current understanding of human ovarian tumorigenesis is limited by the lack of a discrete precursor lesion as well as a limited knowledge of the steps in tumor progression. Since the alterations in the regulation of the tyrosyl residues on various cellular proteins appear to be an important pathway in neoplastic transformation, it is possible that changes in the expression of the proteins that control tyrosine phosphorylation (i.e., tyrosine kinases and phosphatases) may play a role in ovarian cancer development. Protein tyrosine phosphatase, nonreceptor type 6 (PTPN6), contains two src homology 2 domains and is expressed primarily in hematopoietic and epithelial cells. Using Northern blot and immunoblotting analysis, we showed that both the PTPN6 transcripts and proteins were overexpressed two- to four-fold in 7 of the 8 ovarian epithelial carcinoma cell lines studied. In addition, we showed that there was also a two- to threefold increase in expression of the PTPN6 transcript in 10 of 11 (91%) invasive ovarian epithelial cancer tissues examined. These observations suggest that the PTPN6 gene is potentially of etiologic relevance to a majority of ovarian cancers. PMID- 7774832 TI - The subrenal capsule assay in selecting chemotherapy for ovarian cancer: a prospective randomized trial. AB - In order to find out whether the response rate and survival in epithelial ovarian cancer can be improved by aid of sensitivity testing with the subrenal capsule assay (SRCA), 196 patients with FIGO Stage II-IV epithelial ovarian cancer were randomized to be treated with either cyclophosphamide-doxorubicin-cisplatin (CAP) or SRCA-guided chemotherapy. The drug combinations tested with the SRCA were (1) cyclophosphamide-doxorubicin-carboplatin (CACAR), (2) CAP, (3) carboquone methotrexate-tegafur (CQ-MTX-TEG), (4) cisplatin-etoposide-hexamethyl-melamine (P VP-HXM), and (5) bleomycin-epirubicin-cisplatin (BEP). A total of 132 patients (CAP, 69; SRCA, 63) were eligible for efficacy analysis based on relaparotomy findings. The overall response rate was 59% in the CAP arm and 62% in the SRCA arm. In the SRCA arm, 16 patients were treated with CACAR, 24 with CAP, 10 with CQ-MTX-TEG, 11 with P-VP-HXM, and 2 with BEP. The response rate to CACAR was 63% and to SRCA-CAP was 75%. The number of complete responses was higher when CAP was given as guided by the assay than when given at random (14/24 vs 23/69; P = 0.03, Pearson chi 2). Survival curves as estimated by Kaplan-Meier method gave a median survival of 24 (SE = 4) months to the SRCA arm and 28 (SE = 5) for the CAP arm (P = 0.7; log-rank test). Because no survival benefit was achieved, the SRCA obviously needs further development before it can be routinely recommended in the choice of first-line chemotherapy for patients with ovarian cancer. PMID- 7774834 TI - Using a vaginal tube to exteriorize lymph nodes during a laparoscopic pelvic lymphadenectomy. AB - Laparoscopic pelvic lymphadenectomy for gynecological malignancy involves mobilizing and exteriorizing the lymph nodes. We removed the nodes by passing a 4 to 5-cm-diameter tube through the vagina to the abdomen following the hysterectomy. The nodes were passed through the tube rather than pulled through the abdominal ports. The tube is easy to insert and is a valuable conduit for exteriorizing tissue during laparoscopic pelvic surgery for gynecological cancer. PMID- 7774835 TI - Results of postoperative radiation therapy for patients with carcinoma of the uterine cervix: evaluation of intravaginal cone boost with an electron beam. AB - Retrospective analysis was carried out from the records of 108 patients with carcinoma of the uterine cervix treated with postoperative external whole pelvic irradiation (EWPI) followed by intravaginal cone boost with an electron beam to the vaginal cuff (IVCB) to evaluate the efficacy of this method. The 5-year cause specific survival rates were 89% for 89 patients undergoing prophylactic radiation therapy and 56% for 19 patients undergoing salvage radiation therapy (P < 0.001). The 5-year survival rates were 62% for 11 patients with macroscopic residual tumors and 41% for 8 patients with microscopic residual tumors. Of the patients with pelvic lymph node (PLN) involvement, incidences of intrapelvic recurrence, extrapelvic recurrence, and distant metastases were 12, 9, and 3%, respectively. The prognosis for patients without PLN metastasis was significantly better than that for patients with PLN metastasis in the prophylactic radiation therapy group (P < 0.001). Recurrent tumors at the vaginal cuff were observed in only 2 patients in the prophylactic radiation therapy group. Vesicovaginal fistula was observed in 4 patients. Only 1 patient developed Grade 2 rectal complications. No other severe complications were observed. IVCB following EWPI is a safe and effective postoperative radiation therapy technique for patients with cervical cancer. PMID- 7774836 TI - The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients. AB - The purpose of this study was to analyze (1) the prognostic factors for survival of T1 and T2 carcinoma patients and (2) the impact of the initial groin node status for the time to recurrence and site of recurrence. We performed a follow up study on 190 women with a T1 or T2 squamous cell carcinoma of the vulva. Data were obtained on age and general medical condition, the clinical and histological characteristics of the primary tumor and the inguinofemoral lymph nodes, treatment, recurrences, and survival. The standard treatment was radical vulvectomy with bilateral inguinofemoral lymphadenectomy supplemented with postoperative radiotherapy to the primary site, groin, and pelvic side walls if groin metastases were present. Compared to patients without lymph node metastases in the groin, the relative risk of dying within a given time period was estimated to be 2.47 (limits of the 95% confidence interval: 1.24, 4.93) and 9.69 (3.90, 24.03) for patients with unilateral and bilateral node metastases, respectively. The number of metastatic lymph nodes or their intra- or extranodal growth was not associated with survival. The relative risk of dying within a given time period was 2.71 (1.36, 5.40) for patients with a T2 tumor compared to those with a T1 tumor and 2.37 (1.31, 4.31) for patients with vasoinvasive growth compared to those without capillary-lymphatic tumor infiltration. Tumor thickness, differentiation grade, and multifocal growth did not determine survival. In the multivariate Cox regression analysis, the presence of inguinofemoral lymph node metastases proved to be the most important prognostic factor for patients' survival. Of the 119 patients who underwent lymphadenectomy but in whom no groin node metastases were found, 6 (5%) patients manifested an early recurrence (i.e., residual cancer or a recurrence within 2 years after the diagnosis). In contrast, of the 51 patients with histologically documented groin node metastases, 15 (29.4%) manifested an early recurrence and these recurrences appeared equally distributed over the primary site and other sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774837 TI - T2/3 vulva cancer: a case-control study of triple incision versus en bloc radical vulvectomy and inguinal lymphadenectomy. AB - The purpose of this case-control study was to compare outcome in T2/3 vulvar cancer patients treated with radical vulvectomy and inguinal lymphadenectomy using either a triple incision or en bloc technique. All T2/3 vulvar cancer patients treated by the triple incision technique were identified and compared to a control group consisting of similar T2/3 patients treated with an en bloc procedure at the same institution. Survival by surgical stage, lesion diameter, nodal status, and margin status was analyzed and compared between the two groups. Twenty-seven vulvar cancer patients with a T2/3 lesion underwent radical vulvectomy and inguinal lymphadenectomy using the triple incision technique; the control group consisted of 20 T2/3 vulvar cancer patients treated by en bloc resection. The two groups were matched for age, surgical stage, grade, lesion diameter, margin status, nodal status, and adjuvant treatment. The recurrence rate in the triple incision group was 37% compared to 35% in the en bloc group. (OR, 1.092, 95% CI, [0.327, 3.649], P = 0.9). There was no difference in the local recurrence rate between the two groups (80% in the triple incision group and 72% in the en bloc group) (P = 0.5). Five-year survival for the triple incision and the en bloc groups was similar, 64 and 82%, respectively (P = 0.15). Survival between the groups was not statistically different when analyzed according to surgical stage, lesion diameter, nodal status, and negative margin status. These data indicate that the triple incision technique provides survival outcomes similar to the standard en bloc radical vulvectomy in patients with T2/3 vulva cancer. Due to the significant morbidity that has been associated with the en bloc radical vulvectomy and inguinal lymphadenectomy, the triple incision technique should be considered as the preferred method of treatment for most vulvar cancer patients. PMID- 7774838 TI - Gestational trophoblastic tumors of the uterus: MR imaging--pathologic correlation. AB - The purpose of this study is to evaluate the MR findings of gestational trophoblastic tumors (GTTs). Ten patients who confirmed the diagnosis (4 choriocarcinomas and 6 invasive moles) constituted the basis of our study. The MR findings from these patients were prospectively correlated with the histopathology of resected tumor specimens. MR findings of 4 patients with choriocarcinomas were well-defined, hemorrhagic masses with central necrosis. In contrast, 6 patients with invasive moles showed ill-defined, permeative masses with densely enhanced solid components and tiny cystic lesions. The trophoblastic proliferation, coagulation necrosis, and molar villi had varying signal intensities on T1- and T2-weighted images. Our results suggest that MR imaging is a promising tool for noninvasive morphologic analysis of GTTs. PMID- 7774839 TI - The interaction between cytotrophoblasts and their derived tumor cells. AB - Previous experiments demonstrated that human cytotrophoblasts and cells of the choriocarcinoma cell line JAr interact in vitro. As a result of this interaction there is an increased synthesis of CG and hPL, probably as a result of the increased CG and hPL synthesis by the cytotrophoblasts. In the present investigation we studied this interaction in greater detail and found that both cytotrophoblasts and JAr cells undergo changes in their biological properties as a result of this interaction. JAr cells and cytotrophoblasts cocultured for 72 hr were fractionated according to their size by centrifugal elutriation. The number of cells in the fraction which contain the largest cells was very significantly increased as a result of the coculture. This increase was due to an increase in the number of cells of both cell types. This fraction was the most active one in the synthesis of CG and hPL. The synthesis of DNA by the JAr nuclei in this fraction of the cocultured cells was almost completely inhibited but in the parallel fraction of the JAr cells cultivated alone the level of DNA synthesis was equal to that of all other JAr cell fractions. Heterokaryons are formed in the coculture. In these heterokaryons a factor which inhibits DNA synthesis in the cytotrophoblasts may inhibit DNA synthesis in JAr nuclei and at least be partly responsible for the inhibition of DNA synthesis observed. PMID- 7774840 TI - Altered HLA expression by metastatic cervical carcinoma cells as a factor in impaired immune surveillance. AB - The altered expression of histocompatibility leukocyte antigens (HLA) in the development to cervical carcinoma suggests that tumor progression may be related to impaired recognition by host immune defense mechanisms. To investigate whether this phenomenon plays a role in the process of metastasis of cervical cancer, we analyzed and compared the HLA expression with the number of infiltrating immune cells in primary cervical carcinoma and related autologous metastases (n = 30) by staining serial paraffin and corresponding frozen sections with a panel of monoclonal antibodies. In 60% of the cervical metastases, compared to 21% of the primary tumors, a downregulation of monomorphic HLA class I antigens was observed, with frequent allele-specific alterations. In 50% the HLA class II expression was slightly increased on the metastatic tumor cells in comparison to the primary tumor. In addition, variability of alterations in HLA expression was observed between different metastases in the same patient. A minor infiltration of immune cells was present in cervical metastases compared to the primary tumors, especially in the HLA class I-downregulated metastases. Furthermore, loss of HLA class I expression on the metastatic tumor cells resulted in a significant decrease of tumor-infiltrating CD8+ T lymphocytes. These findings suggest that in cervical carcinoma loss of HLA class I expression plays a decisive role in the escape from immune surveillance leading to a greater metastatic potential of tumor cells. PMID- 7774841 TI - Phase II trial of mitomycin-C in squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. AB - Fifty-six patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix not previously exposed to cytotoxic drugs, other than as radiosensitizers, were entered into a study of single-agent 20 mg/m2 mitomycin-C every 6 weeks. The overall response rate among the 52 patients evaluable for response was 12% (three complete and three partial responses). Median response duration was 7.3 months. For the entire population, median progression-free interval was 3.0 months, and median survival was 4.9 months. Among 27 patients with pelvic disease only in previously radiated fields, two responses were observed (7%), whereas four responses were observed among 25 patients with extrapelvic disease in nonradiated fields (16%). The most frequent and severe adverse effects were the result of myelosuppression. Based on the modest level of activity observed, no further study of mitomycin-C in squamous cell carcinoma of the cervix is planned. PMID- 7774842 TI - Urinary tract infection in patients of gynecological malignancies undergoing external pelvic radiotherapy. AB - A total of 216 midstream urine (MSU) samples from 36 patients with gynecological malignancies undergoing external pelvic radiotherapy (RT) were studied periodically every week for any evidence of urinary tract infection (UTI). UTI was detected in 33.3% patients of whom 8.3% had infection at the onset of RT and the rest developed UTI during the course of therapy. All three patients who had UTI at the onset of RT underwent cystoscopy as a part of routine pretreatment workup. A higher preponderance of UTI was observed in patients of stage III carcinoma cervix (33.3%) compared to stage II (16.7%) during the course of RT. Half of the patients with UTI had repeated episodes of infection despite appropriate antibiotic treatment. The study emphasizes the importance of conducting periodic MSU examination in patients with gynecological malignancies during RT and its treatment with appropriate antibiotics to minimize the risks of further injury to the already susceptible uroepithelium following radiotherapy. PMID- 7774843 TI - Induction of immunocellular resistance to IL-2-activated lymphocytes within ovarian carcinoma cells. AB - The development of resistance within ovarian carcinoma cells to activated cytotoxic lymphocytes was the objective of this study. Primary ovarian carcinoma cells were obtained from the ascites of a patient. These cells were cocultured with IL-2-activated autologous tumor-associated lymphocytes (TALs) for 1 week. The resulting selected cells underwent a second coculture for 3 days with IL-2 activated autologous TALs or tumor-infiltrating lymphocytes (TILs). Phenotype analysis of the lymphocytes was performed prior to selection and 4-hr chromium release assays were used to detect resistance induction. Resistance to all effector cells could be demonstrated for the selected cells. However, selected cells maintained in culture demonstrated no difference in cytotoxic susceptibility from unselected cells. The following conclusions were made: (i) rapid immunoselection can occur for ovarian carcinoma in vitro; (ii) the resistance induced is not MHC-restricted; (iii) resistance induced by one type of cytotoxic cell results in general resistance to other types of cell from the same patient; and (iv) this resistance is not maintained during in vitro culture. These results may have direct implications on the future immunotherapy for this condition. PMID- 7774844 TI - Participation in transvaginal ovarian cancer screening: compliance, correlation factors, and costs. AB - The objective was to identify factors influencing participation in screening for ovarian cancer using transvaginal sonography in the free experimental program at the University of Kentucky over its 6+ year history. Database records for screenings, performed from 1987 to June 1994, were utilized. Computer sorts, 1990 census information as predictors, and stepwise multiple regression analysis were employed. Participation in the model ovarian screening program took 3-4 years to approach > 300 screens/month, with repeat screenings exceeding new subject participation in this time period. A number of participants traveled > 200 miles for screening on both initial and repeat encounters. Analysis of distance to the screening site, median family income, county physician population, and education levels indicated that distance and then education correlated best with participation. Unit screening cost shrank from $45 to under $25 when maximal participation was achieved. Distance and education correlated with participation. Expenses compare favorably with diagnostic procedures for other diseases. PMID- 7774845 TI - Blood transfusion and the risk of recurrence in stage IB cervical cancer. AB - The objective of this study is to determine if perioperative blood transfusions increase the risk of recurrence in stage IB cervical cancer. Medical records from all patients with FIGO stage IB cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy (RH + PLND) at the University of Iowa and the University of Nebraska from 1978 to 1990 were retrospectively reviewed. Data collected included patient age, body mass index (BMI), tumor size, cell type, depth of cervical invasion (DOI), presence of capillary-lymphatic space involvement (CLSI), lymph node metastasis, operating time, estimated blood loss, transfusion, and follow-up data. Three hundred two patients underwent RH + PLND. Transfusions were given to 244 (81%), with a mean of 2.6 units (range 1-18 units). Median follow-up was 49.5 months (range 9-190 months). Twenty patients (6.6%) had pelvic nodal metastasis. There were no periaortic nodal metastases in the 101 patients who had periaortic nodes dissected. There were no significant differences between the transfused and nontransfused groups, with respect to age, BMI, DOI, or pelvic node metastasis. Transfused patients differed significantly from the nontransfused in that they had larger tumors (P = 0.047), more frequent CLSI (P = 0.013), longer procedures (P = 0.02), and greater estimated blood loss (P < 0.0001). Recurrences developed in 29 patients (19 pelvic, 7 lung, 3 bone). There is no difference in disease-free survival (DFS) or calculated projected survival between the transfused and nontransfused groups. Pelvic node metastasis and tumor size were independent poor prognosticators. After controlling for these factors, the number of blood transfusions was not predictive of recurrence or survival. Perioperative transfusions do not increase the risk of recurrence in patients with cervical cancer. PMID- 7774846 TI - A phase II trial of piroxantrone in advanced ovarian carcinoma after failure of platinum-based chemotherapy: Southwest Oncology Group Study 8904. AB - A phase II trial of the new anthrapyrazole piroxantrone was conducted by the Southwest Oncology Group in advanced ovarian carcinoma. The objective were to evaluate its response rate and toxicity in patients who had disease persistence, progression, or recurrence either during or after platinum-containing chemotherapy. A two-stage statistical design targeted accrual to 15 eligible patients if no responses were observed. The piroxantrone starting dose was 120 mg/m2, with the provision to escalate to 150 and 180 mg/m2. There were 16 eligible patients, all of whom had received either one (12 patients) or two (4 patients) prior platinum-containing regimens; one patient had received doxorubicin. Fourteen of the 16 patients were enrolled either at the time of disease persistence/progression during initial chemotherapy or with recurrence or progression within 6 months of the previous platinum-based remain. One to 5 cycles of piroxantrone were given. Dose escalation was feasible in 7 patients but was prevented in the other 9 by neutropenia. Maximum toxicity for all cycles was none or grade 1 in 2 patients; grade 2, 5; grade 3, 8; and grade 4, 1. All but one of the grade 3 or 4 events was from myelosuppression; there were no adverse cardiac events. No responses were observed. Thus, piroxantrone appears inactive in patients with persistent, progressive, or recurrent ovarian cancer who recently had received a platinum-based regimen. PMID- 7774848 TI - Successful liver treatment of a juvenile granulosa cell tumor in a 4-year-old child by regional deep hyperthermia, systemic chemotherapy, and irradiation. AB - Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children and adolescents. About 90% are diagnosed in early-stage FIGO I with favorable prognosis. More advanced stages (FIGO II-IV) have a poor clinical outcome and chemotherapy alone cannot avoid tumor progression. Regional deep hyperthermia (RHT) induced by microwave technique has been established as an additional modality for treatment of different tumors. However, in cases with liver involvement there are technical problems which have not yet been solved. We report on a 4-year-old child who suffered from diffuse liver metastases 10 months after JGCT of the left ovary. After chemotherapy including ifosfamide, etoposide, and carboplatin in combination with RHT and consolidation radiotherapy, the patient has been in complete remission for 1 year of follow-up. This Case Report indicates the feasibility of combining surgery, chemotherapy, hyperthermia, and radiation therapy (which can also be an effective treatment modality for advanced granulosa cell tumor) for the treatment of liver metastases of JGCT, but does not allow comparisons of these treatments. PMID- 7774849 TI - Dysgerminoma and gonadal dysgenesis in a 46,XX female with no evidence of Y chromosomal DNA. AB - The occurrence of dysgerminoma in dysgenetic gonads without Y chromosomal influence is exceptionally rare. We used Southern blot hybridization of Y-DNA probes to genomic DNA to search for any Y-related influence in a patient with a dysgerminoma, dysgenetic gonads, and a 46,XX karyotype. No Y-specific DNA was found at 11 loci representing the short arm, centromere, and long arm. This absence of any Y-DNA leaves open to question the absolute requirement of Y related influence in the development of dysgerminoma in dysgenetic gonads. PMID- 7774847 TI - Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study. AB - Thirty-five patients with bulky (designated as > or = 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m2, and vincristine, 1 mg/m2, administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulocytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management. PMID- 7774850 TI - Endometrial squamous cell carcinoma following whole pelvic radiation therapy: response to carboplatin. AB - A case of Stage IV endometrial squamous cell carcinoma occurring 8 years after a low anterior resection and whole pelvic radiation therapy for a Dukes D colon carcinoma is presented. Koilocytosis was present in the tumor. There was no evidence of human papillomavirus antigen or DNA in the tumor. The patient was treated with surgery followed by six cycles of carboplatin chemotherapy. At the completion of chemotherapy there was no clinical or radiological evidence of disease. The tumor recurred 9 months postchemotherapy and the patient died of disease 17 months postdiagnosis. PMID- 7774851 TI - Treatment-related myelodysplastic syndrome following abdominopelvic radiotherapy for endometrial cancer. AB - A patient with grade II endometrial adenocarcinoma underwent TAH/BSO. The tumor penetrated 50% of the myometrium. A lesion from the serosa of the sigmoid colon was removed and contained metastatic adenocarcinoma. Metastatic tumor was also found in the common iliac lymph nodes. Postoperatively the patient was treated with abdominopelvic radiotherapy to 30 Gy. The pelvis was boosted to a dose of 46.2 Gy. The vaginal apex was then treated with three applications of high-dose rate brachytherapy to a total dose of 12 Gy. The patient was doing well with no evidence of recurrence 52 months following treatment when she was diagnosed with a myelodysplastic syndrome. Cytogenetic analysis revealed aberrations of chromosomes 5 and 7, which is highly suggestive of a treatment-related process. Myelodysplasia induced by radiotherapy alone is an unusual but recognized event. PMID- 7774852 TI - Extraovarian stage IV peritoneal serous papillary carcinoma presenting as an asymptomatic skin lesion--a case report and literature review. AB - An 81-year-old G2 P2 white female in good health with the exception of well controlled hypertension presented to her family physician with a newly discovered lesion in the skin of the abdominal left lower quadrant. Initially, this nodule was viewed as innocuous and was followed with the expectation that it would soon resolve. Three months later, the lesion was biopsied, revealing a pattern consistent with papillary serous carcinoma from a presumed ovarian primary. CT scan revealed a pelvic mass. Subsequent laparotomy revealed a benign tubal cystadenofibroma, but otherwise normal pelvic viscera. Additional findings, however, included multiple small parietal peritoneal nodules histopathologically diagnosed as extraovarian peritoneal serous papillary carcinoma similar to the skin lesion. All gross disease was extirpated. The patient received chemotherapy as for advanced ovarian cancer. PMID- 7774853 TI - Onycholysis of the finger and toenails following the application of high-dose oral etoposide (1250 mg/m2) given as 200- and 150-mg single doses from days 1-10 every 3 weeks. PMID- 7774855 TI - Re: Uterine papillary serous carcinoma: patterns of metastatic spread. PMID- 7774854 TI - 12 cases of carcinoid tumors metastatic to the breast have been reported. PMID- 7774856 TI - [Determination of phosphatidylinositol turnover for pharmacological analysis]. AB - The most popular method for determining phosphoinositide hydrolysis is the analysis of water-soluble materials in cells or tissues that have been labeled with [3H]inositol by separating them on anion exchange open columns or HPLC columns. Recently, a radioreceptor assay has become available for the analysis of inositol 1,4,5-trisphosphate (IP3) using IP3 receptors and [3H]IP3; this allows the analysis of IP3 in vivo. On the other hand, radiolabeled phosphoinositides are measured by thin layer chromatography to analyze the breakdown or synthesis of phosphoinositide in response to stimuli. The purified enzyme with phospholipid vesicles can be used to hydrolyze [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) to [3H]IP3, which makes it possible to search for direct action of a drug on phospholipase C. PMID- 7774857 TI - [Hypocalcemic effect of elcatonin in mouse models for humoral hypercalcemia of malignancy]. AB - To elucidate the effect of calcitonin on humoral hypercalcemia of malignancy (HHM), we studied the effect of elcatonin, a synthetic eel calcitonin analog, on plasma calcium concentration in hypercalcemic nude mice transplanted subcutaneously with FA-6 pancreas cancer cells and hypercalcemic mice produced by continuous infusion of parathyroid hormone-related peptide (PTHrP). Elcatonin proved to exert a potent hypocalcemic effect in either model for hypercalcemia. The effect reached peaks at 2 hr after its administration, and it was no longer detected at 24 hr. The dose-dependent effects of a single administration of elcatonin were studied in the FA-6 tumor-bearing mice: the hypocalcemic effect of elcatonin at 1-2 hr after administration was dose-relatedly augmented. The effect of daily administration of elcatonin was further studied in the FA-6 tumor bearing mice: 5-Day daily administration of elcatonin was not accompanied by reduction in its hypocalcemic effect. Moreover, it was suggested that higher the efficacy of elcatonin, the higher were the plasma calcium concentrations in the tumor-bearing mice. These results indicated that elcatonin exerts an immediate hypocalcemic effect even on models for acute and severe hypercalcemia such as FA 6 tumor-bearing mice, that this hypocalcemic effect became more potent depending on their elevation of plasma calcium concentration, and that elcatonin exerts a hypocalcemic effect even on a model for hypercalcemia due to PTHrP, a presumable causative substance of HHM. PMID- 7774858 TI - [A study on the effect of cepharanthin, a biscoclaurine alkaloid, on enhancement of mitogen-induced histidine decarboxylase activity in mice spleens and the effect of histamine on the production of cytokines]. AB - The effect of cepharanthin on the enhancement of mitogen-induced histidine decarboxylase (HDC) activity in mice spleens and the effect of histamine on the production of cytokines were investigated. Cepharanthin enhanced LPS-induced HDC activity in normal mice spleens and also enhanced it in genetically T cell deficient nude mice spleens and T and B cell-deficient scid mice spleens. Therefore, cepharanthin can exert its effect on macrophages without T cells or B cells. Cepharanthin enhanced LPS-induced cytokine production by macrophages. Histamine induced cytokine production and enhanced LPS-induced cytokines production by macrophages. However, diphenhydramine and cimetidine, histamine receptor antagonists, did not block this process. Alpha-fluoromethylhistidine, a suicide inhibitor of HDC, suppressed LPS-induced cytokine production. These results suggest that cytokine production by macrophages is regulated by both histamine added exogenously and histamine induced by macrophages themselves and that histamine participates in enhancement of cytokine production by cepharanthin. PMID- 7774859 TI - [Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats]. AB - The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid. PMID- 7774860 TI - [Studies on histamine H2-receptor antagonistic property of FRG-8813, a novel anti ulcer drug]. AB - The present study was conducted to investigate the histamine H2-receptor antagonistic property of FRG-8813 by using isolated guinea pig right atria, gastric cells and cerebral cortex preparations. FRG-8813 inhibited the histamine induced positive chronotropic response of the right atria and shifted the concentration-response curve of histamine to the right with suppression of the maximal response. Although the inhibitory effect of FRG-8813 was enhanced in a time-dependent manner and long-lasting, the antagonism was reversible. The potency of FRG-8813 was 2 times and 50 times greater than those of famotidine and cimetidine, respectively. FRG-8813 decreased the histamine-induced [14C]aminopyrine accumulation in gastric cells. Schild plot analysis showed that the slopes of FRG-8813, famotidine and cimetidine were 1.56, 1.40 and 1.07, respectively, suggesting that the mode of the antagonism of FRG-8813 is also unsurmountable in gastric cells. The lack of effect on dbcAMP- and bethanechol induced [14C]aminopyrine accumulations indicated the selectivity of FRG-8813 for histamine H2-receptor. As in the right atria, the potency of H2-antagonism was 1.5 times and 40 times greater than those of famotidine and cimetidine, respectively. In the [3H]tiotidine binding study of the cerebral cortex preparation, the Ki values showed that the affinity of FRG-8813 was 2 times and 80 times more potent than those of famotidine and cimetidine, respectively. In conclusion, FRG-8813 is an unsurmountable and selective histamine H2-receptor antagonist with 2 times greater potency than famotidine. The antagonistic activity is reversible in spite of the time-dependent increase of the antagonism. PMID- 7774861 TI - [Hemodynamic and neurohumoral effects of carperitide (alpha-human atrial natriuretic peptide) in dogs with low-output heart failure]. AB - We examined the hemodynamic and neurohumoral effects of carperitide in dogs with low-output heart failure (LHF) produced by volume expansion, ligation of the left anterior descending coronary artery and methoxamine infusion. Carperitide (0.1 approximately 1 micrograms/kg/min, i.v. infusion for 30 min) decreased pulmonary arterial pressure, right atrial pressure and systemic vascular resistance and increased cardiac output. These pharmacological activities were equivalent to those of nitroglycerin (NG, 3 micrograms/kg/min). Although most of the animals did not excrete urine after induction of LHF, carperitide, unlike NG, increased urine volume. The plasma level of cyclic GMP was elevated about three times by induction of LHF and further increased after treatment with carperitide (1 microgram/kg/min). Carperitide had no effects on plasma renin activity, plasma aldosterone concentration and plasma noradrenaline. These results taken together indicate that carperitide reduces both preload and afterload in association with an increase in cyclic GMP production and improves the untoward hemodynamic alterations in LHF dogs. PMID- 7774862 TI - Interaction of cardiac myocytes and non-myocytes in mechanical stress-induced hypertrophy. AB - It is known that mechanical stress directly changes the conformation of the functional proteins, or directly activates enzymes such as phospholipase in the plasma membrane. The integrin-cytoskeleton complex may be an alternative candidate structure for a mechanoreceptor and a transducer. The cytoskeleton has been also shown to play an important role in secretion. Mechanical stress may stimulate the secretion of some cytokines or angiotensin II, which may generate multiple intracellular signals as a secondary event. External stimuli are generally transduced into the nucleus through the activation of protein kinase cascade. Stretching of cardiac myocytes stimulates the activity of PKC, Raf-1 kinase, MAP kinase kinase. MAP kinase and S6 kinase. In cardiac myocytes, mechanical stress directly induces gene expression as well as protein synthesis. Immediate early genes are first induced, and then fetal-type genes are reinduced. Both in hypertrophied hearts and in the experimental model of cardiac hypertrophy induced by pressure overload. Ca(2+)-ATPase content of cardiac myocytes is depressed. Reduced function of sarcoplasmic reticulum causes insufficient decrease of intracellular calcium in diastole and induces slowing of ventricular relaxation. In the interstitium of pressure overloaded hearts, the accumulation of collagen fiber is increased. The abnormal deposit leads to increased chamber stiffness and diastolic dysfunction. Furthermore, TGF-beta and tissue renin angiotensin system are up-regulated in pressure overloaded hearts, both of which accelerate the interstitial fibrosis. PMID- 7774863 TI - Fibronectin expression in the cardiovascular system. AB - Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix (ECM) of most tissues and serves as a bridge between cells and the interstitial collagen meshwork. It also influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of a primary transcript originating from a single gene. The spatial and temporal alterations in FN expression in the cardiovascular system have been studied in vitro in cell culture and in vivo during fetal development, hypertrophy, infarction, arterial injury and aging. This review describes characteristics of FN expression in cardiovascular system: 1. the FN phenotype is regulated during development. A high FN mRNA level is related to an early cardiac organogenesis and a progressive decrease that begins at the fetal stage and continues through senescence. During cardiac ontogeny, there is a linear correlation between total FN mRNA accumulation and the relative amounts of FN EIIIA and EIIIB RNA. This correlation is absent during cardiac growth in the adult. 2. A differential reexpression of the FN isoforms is observed in both myocardium and aorta in different models of hypertension or infarction but with different threshold and time course. Changes in total FN mRNA levels in hypertensive models vary depending on the authors. Nevertheless the differences in the expression of the fetal forms of FN mRNA observed among the various models of hypertension-induced hypertrophy indicate that the process of FN pre-mRNA splicing in the adult myocardium is specifically regulated and depends on the pathological situations and the type of cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774864 TI - Pharmacological modulation of cardiac fibroblast function. AB - The cardiac interstitium is composed of nonmyocyte cells and a structural protein network which plays a dominant role in governing the structure, architecture, and mechanical behavior of the myocardium. The heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for myocardial collagen metabolism and fibrous tissue accumulation, may largely explain the appearance of diastolic and/or systolic myocardial failure. Regulatory mechanisms that are related to the fibrous tissue response in various cardiovascular diseases, e.g., hypertensive heart disease, dilated cardiomyopathy or post myocardial infarction, are of primary clinical interest. A better understanding of the hitherto neglected role of cardiac fibroblasts in mediating an adverse structural remodeling of the myocardium will lead to specific pharmacologic agents that interfere with the fibrous tissue response. Several lines of evidence based on in vivo and in vitro studies suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition or aldosterone receptor antagonism that was found to prevent myocardial fibrosis in the rat with renovascular or genetic hypertension. In cultured adult cardiac fibroblasts, an angiotensin (Ang)II- or aldosterone mediated dose-dependent increase in collagen synthesis could be completely abolished by the use of AngII type 1 or mineralocorticoid receptor antagonists, respectively. Likewise, the AngII-mediated decrease in the activity of matrix metalloproteinase 1, the key enzyme for interstitial collagen degradation, could be antagonized by AngII receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774865 TI - Morphoregulatory interactions of endocardial endothelium and extracellular material in the heart. AB - The endocardium forms the inner lining of the cavities of the heart. The luminal surface of the cardiac wall is subjected to considerable cyclical physico chemical forces. These forces can have structural and physiological consequences both for the endocardial endothelium and for the subjacent interstitial tissue. In the latter tissue space, the extracellular matrix (ECM) plays a dominant role during cardiogenesis. For example, this role becomes evident from the influence of fibronectin in the directional migration of proendocardial cells and in the formation of a trabeculated heart. In particular, the complex processes occurring in the valves of the developing heart illustrate a spatiotemporally regulated expression of ECM components and adhesion molecules. In the adult heart, the endocardial interstitial tissue consists of a thin basal lamina, a reticular lamina and a fibroelastic layer which contains some fibroblasts, smooth muscle cells and a heterogeneous population of nerve fibers. Unlike in arteries, elastic fiber in the fibroelastic layer of ventricular endocardium do not constitute an elastic lamina. Differences in thickness of the endocardium between atria and ventricles, as well as the diffuse and focal endocardial fibrosis during ageing have been related to mechanical stress and local turbulence of flow. Although endocardial fibrosis is a common pathological finding in various cardiomyopathies, our knowledge on the structural organization and on the pathogenetic role of ECM is very limited, mainly by the lack of suitable experimental models. PMID- 7774866 TI - [A new method for occlusion of persistent ductus arteriosus (Botalli)]. PMID- 7774867 TI - [Measures of quality assurance in PTCA]. PMID- 7774868 TI - Extracellular matrix and cardiac interstitium: restriction is not a restricted phenomenon. PMID- 7774869 TI - Local regulation of extracellular matrix structure. AB - The extracellular matrix (ECM) is composed of various collagens, glycosaminoglycans, and elastin bathed by a tissue fluid found throughout the interstitial space. It is this substratum in which fibroblasts and macrophages normally reside, where fibroblast phenotypic transformation occurs, and into which inflammatory cells migrate when called upon during tissue repair. Many diseases, expressed in an organ-specific manner, require organ-specific ECM remodeling. Regulation of fibrillary type I collagen synthesis, whose disproportionate (relative to degradation) accumulation is characteristic of the tissue fibrosis that adversely alters organ function, is therefore of considerable importance. Emerging evidence implicates angiotensin converting enzyme (ACE), found in fibroblast-like cells, and ACE-related peptides, angiotensin II and bradykinin, in serving important regulatory functions that influence wound healing and thereby ECM structure in health and disease. The heart and its collagen matrix have been targeted for discussion in this brief review. PMID- 7774870 TI - Collagen VI in the extracellular matrix of normal and failing human myocardium. AB - Our own previous studies of the composition of the extracellular matrix of human failing hearts showed that collagen VI seems to play a major role in the origin of cardiac fibrosis. Therefore, collagen VI was investigated in more detail in tissue samples taken from clinically normal left ventricle and from myocardium failing because of dilated cardiomyopathy. Tissue sections prepared with collagen VI antibodies were examined by fluorescence microscopy using conventional or confocal laser scanning microscopy. In normal myocardium, collagen VI was located in both, endomysium and perimysium, in blood vessels it surrounded closely individual myocytes. Failing myocardium showed enlargement of the extracellular space and collagen VI was abundant. The localisation was perivascular as well as interstitial in fine or thick bundles enclosing the myocytes completely. In hearts with far progressed failure areas of replacement fibrosis containing increased amounts of collagen VI were evident. Double-staining for vimentin and collagen VI revealed a close interaction with fibroblasts. Although the function of collagen VI is not yet entirely clear it seems obvious that collagen VI plays an important role in the development of fibrosis in the failing heart. PMID- 7774871 TI - [The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction]. AB - The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774872 TI - [Present and future in organ transplantation]. AB - Artificial organs and organ transplantation are the only way to replace the deteriorated function of damaged organs. However, complete replacement of the original functions of organs is not yet possible for artificial organs today, and organ transplantation faces severe scarcity of donor organs. Newly developed immunosuppressant, cyclosporin-A, has contributed to marked improvement in the results of organ transplantation, and organ transplantation is not any more in the stage of experimental therapeutic methods but becomes a choice of routine therapeutic modality for organ failure. The main reason for retarded development of organ transplantation in this country is that organ donation from heart beating cadavers is not yet allowed. However, it is reported that 50 to 60% of Japanese people are ready to accept brain death and organ donation from heart beating cadavers. According to the above described social circumstances, this symposium was organized to overview and discuss the present status and problems in organ, cell transplantation and embryo transfer. I hope that the fruitful results of this symposium will contribute to rapid social and institutional preparations for organ transplantation and to many patients. PMID- 7774873 TI - [Current state in heart transplantation]. AB - The Registry of the International Society for Heart and Lung Transplantation reported that 31,157 transplantations were performed throughout the world until 1993, including 26,704 heart transplantations, 1,567 heart-lung transplantations, 1,943 single lung transplantations and 943 bilateral or double lung transplantations. Heart transplantations were carried out at two hundred fifty one institutes in the world and more than 3,000 patients received heart transplantations every year. The number of heart transplantations, however, became plateau in 1988 and since 1991 the number of operations rather decreased because of the shortage of donor hearts. Indications for adult heart transplantation include coronary artery disease in 47.2% and cardiomyopathy in 43.5%, representing the most frequently reported indications. Retransplantations represent only 2.3% of the total heart transplantations. The results for heart transplantation reveal that the 1, 3, 5, and 12-year actuarial survival are 80%, 72%, 64% and 40%, respectively. Comparing the data before and after 1982 when cyclopropane was introduced for transplantations, a substantial improvement in actuarial survival is obtained. For instance, 3-year actuarial survival before 1981 was 40% whereas since 1982 3-year actuarial survival is improved up to 75%. However, the patients in the older age (more than 65 years old) and pediatric patients, particularly less than one year old, have a significant reduction in outcome compared with younger adult patients and the outcome of heart retransplantation was still poor. Because of the shortage of donor heart quite a large number of patients develop hemodynamic deteriorations before transplantation and mechanical assist device is one of strategies to treat these patients as bridge to heart transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774874 TI - [Hepatocyte transplantation]. AB - Hepatocyte transplantation has been studied to treat patients with liver disorders which do not need total replacement of the liver. We found that intrasplenically transplanted hepatocytes recomposed liver tissues in the spleens of rats and that they revealed similar structure and function of the liver. We also successfully transplanted hepatocytes into the spleens of rats which were isolated from cirrhotic livers or were thawed after long term cryopreservation. We developed the method to isolate human hepatocytes from resected liver tissues and made clinical trials of intrasplenic hepatocyte transplantation for the patients with chronic liver disorders. We detected the survival of transplanted hepatocytes in the spleens of patients, however, further proliferation of them has not yet identified. Hepatocyte transplantation still has many unresolved problems before its clinical application, such as a method to stimulate the proliferation of transplanted hepatocytes enough to make functional support of the damaged livers. In this article, I will review the present status and future aspects of hepatocyte transplantation. PMID- 7774875 TI - [Kidney transplantation]. AB - From March 1986 to August 1994, 110 living-related renal transplants were performed under the cyclosporine combination immunosuppression. Age of the recipients ranged from 4 to 48 years old (mean 29.3), and 81 patients were male and 29 were female. The mean duration on dialysis before the transplants were 39.7 months (0 to 210), and the methods of dialysis were divided with hemodialysis in 94 patients, CAPD in 15 and no dialysis in 1. The donors consisted of 96 parents (87.3%), 66 mothers and 30 fathers, and 14 siblings (12.7%). Age of the donors ranged from 28 to 73 years old (mean 48.7). The number of patients with acute rejection episodes were 48 patients with once, 18 with twice, 10 with 3 times and 34 (30.9%) with no rejection. Patient survival rate was 99.0% after 1 year posttransplantation, 97.9% after 3 years and 95.7% after 5 years. Graft survival rate was 91.5%, 85.1% and 77.8%, respectively. Twenty grafts were lost with the most common causes of graft loss being chronic rejection (55%), acute rejection (20%) and accelerated acute rejection (15%). In cadaveric renal transplants, because of very small number of informations for cadaver donor, only 13 cadaveric renal transplants were performed in Hokkaido, from 1984 to August 1994. There was no case over 5 years follow up postoperatively, so patient survival rate was 100% and 90% after 1 year and 3 years posttransplantation, and graft survival rate was 84.6% and 74.0%, respectively. Two kidneys of 13 cadaveric renal transplants were never functioning grafts. We have to make more efforts for propagation of the donation system. PMID- 7774877 TI - [Assisted reproductive technology; IVF-ET]. AB - To summarize the procedures and outcomes of assisted reproductive technology (ART). Novel and updated ART for the practical management of infertile couples are presented and compared with conventional modalities. The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, still birth and delivery. Of ART treatments, 19,319 cycles initiated was IVF with 12.7% clinical pregnancy per retrieval in the world in 1991. In Japan, pregnancy rate of 9,667 cycles with IVF was 12.7% in 1991. 300 cycles initiated was IVF with 20% pregnancy rate at the Department of Obstetrics and Gynecology, Asahikawa Medical College in 1994. In 1995, there will be more program offering more treatments cycles of ART. Improvements in stimulation, the culture system for fertilization and embryo growth, cryopreservation and microinsemination are expected to enhance the rates of clinical pregnancy. PMID- 7774876 TI - [Hematopoietic stem cell transplantation]. AB - Recent development of chemotherapy enabled us to cure patients with malignancies including leukemia, malignant lymphoma, choriocarcinoma, ovarian cancer, breast cancer and so on. In order to obtain the definite effect, the quantities of chemotherapeutic agents should be increased and the major lethal side effect caused by bone marrow failure should be avoided. For this purpose, hematopoietic stem cells derived from either bone marrow or peripheral blood can be used for the rapid recovery of neutropenia and thrombocytopenia. We prepared stem cells both from bone marrow and peripheral blood by anti-CD34 monoclonal antibody bound on magnetic beads column and administered into severe combined immunodeficiency (SCID) mouse. Four and 20 weeks after transplantation, mononuclear cells bearing human hematopoietic antigens and human immunoglobulin G were appeared in the circulation, suggesting that stem cells from peripheral blood also possess long standing capability of maturation as well as those from bone marrow. We next conducted clinical study of high dose chemotherapy combined with peripheral blood stem cell transplantation for patients with poor risk choriocarcioma. By this treatment, 4 complete response (CR) and 4 partial response (PR) were obtained, whereas 2 progressive disease (PD), 1 no change (NC) and 5 PR were obtained by the previous conventional chemotherapies. The results obtained were promising and this treatment regimen may become a good modality for the complete treatment of chemotherapy curable tumors. PMID- 7774878 TI - [Molecular cloning and functional expression of a mouse adrenocorticotropin receptor gene]. AB - Human genes for an adrenocorticotropin (ACTH) receptor and a melanocyte stimulating hormone (MSH) receptor, and a mouse gene for a MSH receptor have been cloned recently. They constitute a family of receptors for peptides derived from proopiomelanocortin. The ACTH receptor mRNA and the MSH receptor mRNA were expressed only in the adrenal and melanocytes, respectively. Thereafter, three novel receptor genes for melanocortins were molecularly cloned and were expressed exclusively in the brain but not in the adrenal or melanocytes. It has remained unknown how these receptors are differentially expressed in specialized cell type. An adrenocortical cell line of mouse origin, Y-1, is to date the sole cell line which shows responsiveness to ACTH resulting in the induction of steroids. For analysis of the transcriptional regulation of ACTH receptor in Y-1 cells, I have isolated the mouse ACTH receptor gene. A 914 bp DNA fragment of the human ACTH receptor gene was amplified by polymerase chain reaction and used as a probe. Eight positive clones were obtained by screening 10(6) phage clones of a mouse genomic library under the condition of low stringency. One phage clone, lambda mCTR8 which gave the most intense hybridization signal was analyzed. It contained an approximately 12 kb insert. By comparing it with the previously reported human ACTH receptor gene and bovine ACTH receptor cDNA, the mouse homologue is intron-less in its coding region, and has a potential to encode for a 296-amino-acid polypeptide which possesses 88.9% and 78.7% identities to the human and bovine ACTH receptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774879 TI - [Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells]. AB - Although tumor necrosis factor-alpha (TNF) has been applied to early clinical trials for patients with malignant glioma, majority of human glioma cells has been reported to be resistant to TNF cytocidal effect in vitro. This study investigated antiproliferative effect of the TNF associated with induction of differentiation and expression of two distinct TNF receptors on human glioblastoma cell lines. The expression of p55 and p75 TNF receptors on 12 human glioblastoma cell lines was assessed by polymerase chain reaction and flow cytometry. p55 TNF receptor was detected in all cell lines, and only 4 cell lines concomitantly expressed p75 TNF receptor. Twelve human glioblastoma cell lines were treated with low-dose TNF, up to 256 U/ml for 7 days. TNF did not exhibit its cytocidal effect, but showed antiproliferative effects with inhibition of DNA synthesis in majority of cell lines tested. Flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique demonstrated that this antiproliferative effect of TNF was attributed to accumulation of glioblastoma cells in G0/G1 phase, suppressing the proliferative pathway. Furthermore the TNF stimulation increased glial fibrillary acidic protein and production of bioactive molecules including interleukin(IL)-6, IL-8, granulocyte-macrophage colony stimulating factor, prostaglandin E2 and manganous superoxide dismutase. In conclusion, human glioblastoma cells had p55 TNF receptor as a functional receptor and well responded to low-dose TNF stimulation, but not susceptible TNF cytocydal effect. The effect of TNF on glioblastoma cells appeared to modulate cell differentiation. TNF may be utilized as an agent for a differentiation therapy for human glioblastomas. PMID- 7774880 TI - [Promiscuous T cell hybridoma derived from NOD mouse]. AB - In previous studies of this laboratory, epitope (site contacts with TCR) and agretope (site contacts with MHC molecule) were determined on p43-58 peptide composed of residues 43 to 58 of pigeon cytochrome c. Position 50 was shown to be a major epitopic site. Positions 46 and 54 were agretopic sites and we could determine specific amino acids on the agretopic positions which bound to each relevant I-A or I-E molecule. Using NOD mice, amino acids on the agretopic positions bound to I-Ag7 molecules were analyzed. Arginine (R) at position 46 and alanine (A) at position 54 were shown to be an agretopic motif bound to I-Ag7 molecules. I then established hybridomas specific for a p43-58 analogue, 46R50E54A, which contains R, glutamic acid (E) and A at positions 46, 50 and 54, respectively. Among the 46R50E54A-specific T cell hybridomas, a highly promiscuous hybridoma, NOE33-1-2, which recognized 46R50E54A with a variety of I A molecules (I-Ad,s,u,v) as well as with I-Ag7 was obtained. Interestingly, NOE33 1-2 cells exhibited almost same responding pattern to various 46R50E54A analogue peptides as bulk lymph node T cells from each I-A bearing mice immunized with a 46R50E54A analogue did. Thus, the responding pattern of NOE33-1-2 appeared to be simply reflected by the binding affinity of the 46R50E54A analogues to the relevant I-A molecule. However, subsequent analysis with I-Ad and mutant I-Ad expressing antigen presenting cells (APC) showed that the floor part of beta chain of the I-Ad molecule was profoundly involved in interaction among TCR of NOE33-1-2, 46R50E54A and the I-Ad molecule. On the other hand, this part appeared not to be important in responses of all other 46R50E54A-specific and I-Ad restricted T cell hybridomas derived from I-Ad or I-Ab mice. No difference was shown in the expression of accessory molecules which might interpret the queer interaction between TCR of NOE33-1-2, antigenic peptide and MHC molecule. When NOE33-1-2 cells were competed with T cell hybridomas derived from I-Ad mice for I Ad plus peptide Ag, the TCR of NOE33-1-2 cells showed higher affinity to the stimulatory complexes than that of latter hybridoma cells. These findings suggest that NOE33-1-2 hybridoma cells are of peculiar characteristics which may be attributable to negative or positive selection under influence of I-Ag7 molecules. PMID- 7774881 TI - [Studies on the regulation of glycolipid sulfotransferase activity in human renal cancer cells]. AB - In the previous studies, epidermal growth factor (EGF) was found to elevate glycolipid sulfotransferase activity in a human renal cell carcinoma cell line, SMKT-R3. To elucidate whether Ras is involved in the signal transduction pathway from EGF to the expression of the sulfotransferase, effects of EGF and a tyrosine kinase inhibitor on the sulfotransferase activity were investigated in renal cancer cells stably expressing activated Ras. SMKT-R3 cells were transfected with a plasmid carrying v-H-ras (pv-H-ras). As a control, SMKT-R3 cells transfected with a mutant v-H-ras, in which glycine at position 15 was replaced by valine (pG15V), was used. The expression of v-H-ras in transfected cells was examined by RT-PCR analysis. Two clones transfected with pv-H-ras, named A1 and A6, and two clones transfected with pG15 V, termed B1 and B4, were found to express v-H-ras and G15V genes, respectively, and employed in the following experiments. Though EGF elevated the activity of glycolipid sulfotransferase in B1, B4 and SMKT-R3 cells, it did not change the activity levels in A1 and A6 cells. This result suggested that since the signal from Ras was saturated in the cells expressing activated Ras, the cells did not respond to the stimulation by EGF. To know the association between tyrosine kinase of EGF receptor and Ras, the effect of Genistein, a specific inhibitor of tyrosine kinase, on the sulfotransferase activity was examined in these cell lines. Genistein reduced the activity of glycolipid sulfotransferase in B1, B4, and SMKT-R3 cells, whereas it hardly affected the sulfotransferase activity in A1 and A6 cells. This result indicated that the signal from tyrosine kinase was dissociated from the regulation of the sulfotransferase activity in the cells expressing activated Ras. These observations suggest that Ras is involved in the signal transduction from EGF to the expression of glycolipid sulfotransferase activity in SMKT-R3 cells and acts in the downstream of tyrosine kinase of EGF receptor. PMID- 7774882 TI - [Establishment and analysis of cell culture infected persistently with JC virus]. AB - JC polyomavirus (JCV) is the causative agent of a demyelinating disease in the central nervous system, known as progressive multifocal leukoencephalopathy. Since it is difficult to propagate JCV in vitro, many laboratories have attempted to develop cell lines permissive for replication of JCV. It was recently reported that serial passage of JCV (strain Mad-1) in a human neuroblastoma cell line (IMR 32 cells) generated JCV variants (M1-IMRa, -IMRb, -IMRc) adapted to the growth in IMR-32 cells. We obtained a persistently-infected cell culture, designated JCI cells, by continued subcultivation of IMR-32 cells which had been infected with these adapted variants. To understand the mechanism by which the carrier state was maintained, we molecularly cloned multiple JCV DNAs from JCI cells. Sequencing of the cloned DNAs revealed that a majority of the clones had the same altered regulatory sequence which was probably generated from M1-IMRa. A DNA transfection experiment using a chimeric JCV DNA, in which the regulatory region was derived from JCI and the other region from Mad-1, showed that the JCI regulatory region was less efficient in inducing virus production in IMR-32 cells. Therefore, it could be concluded that the regulatory region is primarily important for maintaining the carrier state in JCI cells. Although JCI cells contained a significant amount of JCV, the yield of JCV could remarkably be increased by incubating a confluent JCI culture in a medium with a low serum concentration. Thus, JCI cells should greatly facilitate the production of JCV for future studies of the virus. PMID- 7774883 TI - [Epstein-Barr virus-specific immunity in asymptomatic carriers of human T-cell leukemia virus type 1]. AB - Adult T-cell leukemia (ATL) patients are immunosuppressed as evidenced by anergy to recall antigens and the occurrence of opportunistic infections. The immunosuppression appears to be a critical factor or a predictive sign for the development of ATL in carriers of human T-cell leukemia virus type 1 (HTLV-1). This study was aimed at assessing the immune status of asymptomatic HTLV-1 carriers with the immunity specific to Epstein-Barr virus (EBV), a ubiquitous human herpesvirus with oncogenic potential. Forty-three asymptomatic HTLV-I carriers were examined for their EBV serology and EBV-specific cytotoxic T-cell (EBV-CTL) activity, in comparison with 10 HTLV-I-non-infected normal controls. Both carriers and controls were all positive for EBV capsid antigen (VCA) IgG. Significantly elevated titer of VCAIgG and lower titer of EBV-determined nuclear antigen (EBNA) antibodies were observed in asymptomatic HTLV-I carriers, suggesting reactivation of EBV. Among the HTLV-I carriers, 9 (20.9%) had reduced activity of EBV-CTL as revealed by lower incidence of regression of in vitro EBV induced B-cell transformation. Accordingly, asymptomatic HTLV-I carriers were divided into three groups: the carriers with reduced EBV-specific cellular immunity (group I), the carriers showing normal cellular immunity but aberrant EBV-specific antibody titers (group II), and the carriers with normal EBV specific cellular immunity and serology (group III). Higher positive rate of anti HTLV-I Tax antibody was found in the former two groups (44.4% and 56.5%, respectively) compared with group III (18.2%). An immunosuppressive agent, 4 deoxyphorbol ester induced a remarkable decrease of EBV-CTL activity in the carriers of group II and III at the concentration that affected none of the normal controls. These findings indicate that asymptomatic HTLV-I carriers suffer stepwise impairment of EBV-specific immunities, which may be caused by HTLV-I infection. PMID- 7774884 TI - [Determination of a peptide deduced from the influenza virus haemagglutinin that induces human class II-restricted T cell responses in DQ6 transgenic mice]. AB - HLA-DQ6 (DQ6) transgenic mice were immunized with a set of peptides deduced from either a fragment of the haemagglutinin (HA) of influenza A/Aichi/2/68 virus (HA123-138) or pigeon cytochrome c 43-58 (p43-58) analogues. HA123-138 induced a moderate level of T cell responses in DQ6 transgenic mice. The T cell responses were shown to be restricted to either the DQ6 or I-Ab molecule. We then established T cell hybridomas specific for HA123-138 and restricted to DQ6 from DQ6 transgenic mice immunized with the HA123-138. These T cell hybridomas were activated by the stimulation with HA123-138 in the presence of an HLA-DQ6 transfectant or a paraformaldehyde-fixed HLA-DQ6 positive EB cell line. Using one of these T cell hybridomas we searched for potent peptides which showed high antigenicity as compared with HA123-138. We found that a hybrid peptide antigen, 46F/HA126-134/54A, which was composed of HA126-134 and the I-Ab binding component (46F/54A) previously determined on p43-58 analogues evoked considerable responses in the HA123-138 specific T cell hybridoma. Competitive inhibition assay with this T cell hybridoma and direct binding assay using a DQ6 positive EB cell line or DQ6-transfected L cells showed consistently that the agretopic position 46 of the p43-58 analogues and hybrid peptide antigens was preserved among DQ6 restricted T cell responses and murine class II, I-A, restricted T cell responses. Phenylalanine (F) at the position 46 appeared to be a critical residue for binding to HLA-DQ6 as had been shown for binding to I-Ab. PMID- 7774885 TI - Pathobiological determinants of cocaine-associated cardiovascular syndromes. PMID- 7774886 TI - Tophaceous pseudogout (tumoral calcium pyrophosphate dihydrate crystal deposition disease). AB - Most cases of calcium deposition seen radiologically in soft tissues are caused by calcium hydroxyapatite and occur either as a complication of trauma with associated necrosis (eg, fat necrosis), generalized connective tissue diseases (eg, scleroderma), metabolic disturbances (eg, hyperparathyroidism, familial hyperphosphatemia), sarcoidosis, myeloma, or metastases. Hydroxyapatite deposits are seen at many soft tissue sites, including joint capsules, ligaments, blood vessels, dermis, etc. On the other hand, deposits of calcium pyrophosphate are seen typically in the meniscus, articular cartilage, ligamentum flavum, and intervertebral disc. They usually are punctate or linear in distribution within the meniscus or parallel to the subchondral bone end plate. We report seven cases of massive focal calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (tophaceous pseudogout) that occurred in atypical locations for CPPD. The ages of the patients ranged from 31 to 86 years (average, 60.7 years). One patient was male and six were female. The temporomandibular joint was involved in three patients and the metatarsophalangeal joint of the great toe was involved in two patients. The hip joint and cervical spine were involved in one patient each. A mass or swelling with or without pain was a common symptom. None of the patients in our series had clinical or radiographic evidence of CPPD crystal deposition disease in any other joints. Roentgenograms showed calcified lesions with a granular or fluffy pattern. Histologically, the lesions showed small or large deposits of intensely basophilic calcified material containing needle shaped and rhomboid crystals with weakly positive birefringence characteristic of CPPD. Foreign body granulomatous reaction to the CPPD deposition was constantly found. Chondroid metaplasia around and in the areas of CPPD deposition was observed commonly. Some of the chondroid areas showed cellular atypia in chondrocytes suggestive of a malignant cartilage tumor. It is important to recognize this rare form of CPPD crystal deposition disease and to identify the CPPD crystals in the calcified deposits, thus avoiding the misdiagnosis of benign or malignant cartilaginous lesions. PMID- 7774887 TI - Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. AB - Pre-eclampsia/toxemia (PET) is an idiopathic hypertensive disorder of pregnancy elicited in susceptible mothers by exposure to placental trophoblast. Three facts regarding the placenta in PET are known: an association with large placentas (excessive trophoblast), a tendency for superficial implantation, and inappropriate trophoblastic immaturity, as assessed by ultrastructural and biochemical criteria. A unitary hypothesis is that PET is related to a maturation defect leading to excessive accumulation of inappropriately immature intermediate trophoblast in the placental implantation site. We studied the implantation site of PET and control placentas from three gestational age groups (25 to 30, 30 to 35, and 36 to 40 weeks old [five per group]) by morphometry and immunohistochemistry using antibodies to three phenotypic markers (cytokeratin, human placental lactogen (HPL), and beta 2-microglobulin) and two markers of cell dynamics (proliferating cell nuclear antigen [PCNA] and bcl-2]). Implantation sites in the PET group had increased amounts of intermediate trophoblast (cell number and longitudinal extent) with an increased proliferative index (percentage of PCNA positive) and evidence of phenotypic immaturity (HPL negative). Intermediate trophoblast from both groups was uniformly bcl-2 negative and beta 2 microglobulin positive. Based on these data and the findings of other investigators, we propose that the diagnostic term "atypical implantation site" be added to acute atherosis, villous infarction, and increased syncytial knotting as a characteristic of placentas from pre-eclamptic pregnancies. PMID- 7774889 TI - Nonfamilial tumoral calcinosis associated with chronic renal failure and secondary hyperparathyroidism: report of two cases with clinicopathological, immunohistochemical, and electron microscopic findings. AB - The clinical and pathological findings, including those of immunohistochemical and ultrastructural studies, of two cases of tumoral calcinosis-like lesion (TCL) are described. Both cases were associated with chronic renal failure and hyperparathyroidism. One case presented as a rapidly growing 20-cm multiloculated, cystic, calcific gluteal mass on the sacrum, which was not clinically suspected to be related to hyperparathyroidism. The other case presented as a 2.5-cm calcific mass on the right foot that recurred after surgical excision as a 7-cm mass, which was clinically presumed to be related to secondary hyperparathyroidism. Light microscopic and immunohistochemical studies on both cases and ultrastructural studies on one case indicated that the calcifying process involved histiocytes and osteoclast-like giant cells of histiocytic origin lining the cystic cavities. Hydroxyapatite crystal formation and calcification appeared to develop predominantly from intracytoplasmic membrane bound vesicles and also from mitochondria. These findings are similar to those recently reported for familial tumoral calcinosis, which support its having a mechanism of calcification comparable with that of a TCL. PMID- 7774888 TI - neu overexpression correlates with extent of disease in large cell ductal carcinoma in situ of the breast. AB - In a retrospective study of ductal carcinoma in situ (DCIS) of the breast, the expression of the neu oncogene was determined immunohistochemically in 76 women treated by local excision or mastectomy. The histopathological features, including the extent of the lesion, histological subtype, cell type, and number of mitoses, were related to neu overexpression. Immunopositivity was found only in DCIS of large cell type, where it correlated with extent of disease but not with mitotic rate. Our findings, together with previous experimental evidence, suggest that this relationship is a consequence of the effect of the neu protein on cell motility. PMID- 7774890 TI - CD30-positive anaplastic large cell lymphoma in a human T-cell lymphotropic virus I endemic area. AB - Clinicopathological and cytogenetic studies were performed on specimens from 43 patients with CD30-positive anaplastic large cell lymphoma (ALCL). All patients were born and lived in a human T-cell lymphotropic virus (HTLV)-I endemic area. Twenty-one patients (48.8%) had serum anti-HTLV-I antibody suggesting the presence of adult T-cell leukemia/lymphoma (ATL). Seventeen of them showed a clonal integration of complete HTLV-I proviral DNA by the Southern blot hybridization method in materials obtained by biopsy. Their ages ranged from 37 to 81 years (median, 67.0), and they frequently presented with lymphadenopathy (82.4%) and extranodal tumors with (76.5%) as well as with rare leukemic changes (5.9%). Immunohistologically the lymphoma cells in 15 ATL patients showed a T cell phenotype. In only one patient (5.9%) was there an expression of epithelial membrane antigen (EMA) in most of the lymphoma cells. Cytogenetically aberration of chromosome band 5q35 was not found in seven patients with HTLV-I proviral DNA. The overall median length of survival was 11.9 months for the patients with HTLV I proviral DNA, indicating a worse prognosis compared with that of the age matched patients with negative anti-HTLV-I antibody (P < .01). The specimens of the patients with HTLV-I proviral DNA had unique clinicopathological and cytogenetic features. These findings suggested that T-cell ALCL with HTLV-I proviral DNA should be considered to represent the lymphoma type of ATL. PMID- 7774891 TI - p53 expression and DNA ploidy of cartilage lesions. AB - The aim of this study was to investigate the expression of a tumor suppressor gene (p53) in cartilage lesions of bone and its relationship to their histological grade and DNA ploidy. An immunohistochemical assay for p53 and Feulgen-stained DNA preparations was subjected to computerized image analysis. Enchondromas, synovial chondromatosis, and low grade (grade I and II) chondrosarcomas were diploid. High grade (grade III) chondrosarcomas and high grade sarcomatous components of dedifferentiated chondrosarcomas were aneuploid. Well differentiated cartilaginous components of dedifferentiated chondrosarcomas were diploid. Microscopic examination showed weak focal positivity for p53 in one of 10 enchondromas one of six examples of synovial chondromatosis, and three of four low grade (grade I and II) chondrosarcomas. All three high grade (grade III) chondrosarcomas were strongly positive for p53. The high grade sarcomatous component of all four dedifferentiated chondrosarcomas was strongly positive for p53, whereas only focal weak positivity was noted in the well differentiated cartilaginous areas. These results were confirmed by quantitative computer assisted image analysis, which showed that high grade aneuploid cartilage tumors demonstrated strikingly higher levels of p53 than did diploid low grade malignant tumors or benign cartilage lesions. PMID- 7774892 TI - Nodal benign and malignant monocytoid B cells with and without follicular lymphomas: a comparative study of follicular colonization, light chain restriction, bcl-2, and t(14;18) in 39 cases. AB - As part of an effort to develop a better understanding of the relationship between nodal monocytoid B-cell lymphomas (MBCLs) and follicular lymphomas (FLs) when they coexist (MBCL + FL) and to assess the validity of the morphological criteria for the latter diagnosis, we evaluated follicular colonization, bcl-2 reactivity, light chain restriction, and the presence of t(14;18) in 14 benign lymph node specimens containing benign monoclonal B cells (MBCs), in eight nodal specimens of pure MBCL, and in 17 nodal specimens of MBCL coexisting with FL (MBCL + FL). Follicular colonization by malignant MBCs was observed in six specimens of pure MBCL and in 13 specimens of MBCL + FL. Benign MBCs did not express bcl-2 by immunohistological methods in 11 of 12 benign specimens. In contrast, weak reactivity for bcl-2 was detected in malignant MBCs in four of five specimens of pure MBCL and in the MBCL component in 13 of 15 specimens from the MBCL + FL group. In the FL component of 13 specimens, the bcl-2 was strongly positive. Identical light chain restriction was detected by immunohistological methods in both the FL component and the MBCL component in 15 specimens of MBCL + FL. Polymerase chain reaction analysis did not detect the t(14;18) translocation in any of 10 benign specimens or any of six evaluable pure MBCL specimens. In contrast, the translocation was detected in whole sections from eight of 12 specimens of MBCL + FL. Thus, on the one hand, the high incidences of follicular colonization and the coexistence of MBCL and FL as well as the identical light chain restriction in MBCL and FL components of MBCL + FL cases suggest that possibly these are related closely when they coexist. On the other hand, the bcl 2 and t(14;18) data cannot be used as evidence in support of a close relationship. PMID- 7774893 TI - Vasculitis as the basis of cutaneous lesions in Reiter's disease. AB - The cutaneous lesions of Reiter's disease (RD) and pustular psoriasis (PP) are said to be histologically similar and often indistinguishable. We encountered three cases of RD in which biopsy specimens of lesions clinically compatible with keratoderma blenorrhagicum showed a pustular psoriasiform tissue reaction in conjunction with a subjacent superficial leukocytoclastic vasculitis (LCV). In an attempt to ascertain if these changes were distinctive and unique to cutaneous RD, the incidence of such changes in lesions of PP was examined using light microscopy and immunohistochemistry. The role of chlamydial infection in the pathogenesis of the observed vascular changes also was explored by assessing for the presence or absence of vascular deposition of chlamydial antigen in cutaneous RD compared with that in a control group that included cases of LCV and PP. In addition to conventional light microscopic analysis, immunoperoxidase studies to identify immunoglobulin deposition were performed on formalin-fixed, paraffin embedded tissue from two of three patients with RD and on skin biopsy specimens from 11 patients with PP. Direct immunofluorescence (DIF) studies with antibodies to immunoglobulin (Ig)G, IgM, IgA, C3, and chlamydial antigens were performed on frozen tissue from one patient with RD, two patients with PP, three patients with LCV, one patient with nonspecific dermatitis, and one patient with Behcet's disease, who had a high antichlamydia antibody titer. All three specimens of RD showed a pustular psoriasiform diathesis in conjunction with a subjacent superficial LCV that was of maximal intensity in the dermal papillae capillaries. Through an immunoperoxidase technique performed on formalin-fixed tissue, the RD cases for which tissue was available for study demonstrated Ig deposition in injured blood vessels; using the same technique one of 11 PP biopsy specimens showed vascular Ig deposition in concert with LCV. This patient's biopsy was from a lesion of drug-induced LCV. None of the other specimens showed either light microscopic or immunohistochemical evidence of vasculitis. In the one specimen of RD studied by DIF, vascular deposition of IgG, IgM, C3, chlamydia heat shock protein 60 (CHSP60), and chlamydia-specific lipopolysaccharide (LPS) was observed. In the two specimens of PP studied, vascular deposition of C3, fibrin, CHSP 60, and chlamydia-specific LPS was not observed. Two specimens of LCV and the one specimen of dermatitis with concomitant nonspecific vascular injury showed vascular Ig and C3 deposition; in contrast, no vascular deposition of CHSP 60 or chlamydia-specific LPS was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774894 TI - Is esthesioneuroblastoma a peripheral neuroectodermal tumor? AB - Esthesioneuroblastoma (ENB; olfactory neuroblastoma) is a rare, locally aggressive neoplasm of the sinonasal area and anterior cranial fossa. The histogenesis of the lesion is not clearly delineated, and the broad histological spectrum of ENB has confounded the issue. The location, histological features (neuropil, Homer Wright, and olfactory rosettes), and reported immunocytochemical reactions (neuron-specific enolase (NSE) and chromogranin (CHR) positivity) suggest that ENB may be a neural or neuroendocrine neoplasm derived from the olfactory membrane. Recent demonstration in two of three metastatic putative ENB cell lines of the 11;22 chromosomal translocation, seen in Ewing's sarcoma (ES) of bone and peripheral neuroectodermal tumors (PNET) of bone and soft tissue, has led to the conclusion that ENB may be closely related histogenetically to PNET. The overwhelming majority of cases of ES and PNET express the protein product of MIC-2, a gene located on the pseudoautosomal region of the X and Y chromosomes. This protein can be identified immunocytochemically by antibodies 12E7, HBA71, and ON13. We studied the expression of MIC-2 using the 12E7 antibody as well as multiple neural markers in 18 ENB samples obtained from the files of The Johns Hopkins Hospital. The patients ranged in age from 19 to 90 years (mean, 47.5; median, 47) and included five men and 13 women. None of the 18 specimens reacted with antibody 12E7, but 16 were positive for NSE, nine reacted to synaptophysin (SYN), and 13 showed antibodies to chromogranin (CHR). Our studies agree with the previous suggestions that ENB is a primitive neural tumor but fail to support the hypothesis that it is a member of the PNET family. PMID- 7774895 TI - Ductal carcinoma in situ treated with lumpectomy and irradiation: histopathological analysis of 49 specimens with emphasis on risk factors and long term results. AB - Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7774896 TI - Association of human papillomavirus with malignant and premalignant lesions of the uterine endometrium. AB - The possible association of human papillomavirus (HPV) with endometrial hyperplasia and endometrial adenocarcinoma was investigated. DNA from frozen tissues of 30 endometrioid carcinomas of Japanese patients was tested for HPV DNA by Southern blot hybridization analysis. Screening with HPV type 58 probe under low stringency conditions showed the presence of HPV DNA in two of 30 endometrioid carcinomas. High stringency hybridization identified HPV type 16 in the two positive specimens. The presence of HPV was further analyzed by polymerase chain reaction (PCR)-Southern blot analysis of DNA from archival tissue blocks of the initial 30 endometrioid carcinomas as well as an additional 17 endometrioid carcinomas and 13 atypical hyperplasias of the endometrium from Japan and 38 endometrioid carcinomas from the United States. Polymerase chain reaction amplification using type 16-specific HPV primers for a portion of the E6 open reading frame was positive in six of 47 (13%) endometrioid carcinomas from Japan, including two in which HPV 16 was not detected by Southern blot analysis and two of 38 (5%) endometrioid carcinomas from the United States. Polymerase chain reaction amplification using L1 consensus sequence primers was positive for HPV in two of 13 (15%) endometrial hyperplasias, 13 of 47 (28%) endometrioid carcinomas from Japan, and six of 38 (16%) endometrioid carcinomas from the United States. Slot blot hybridization identified HPV type 16 in seven of the L1 PCR products, including all but one specimen testing positive for HPV type, 16 using E6 type specific primers. In situ hybridization was positive for HPVs 16/18 in glandular epithelial tumor cells in six of the PCR-positive specimens. An additional specimen showed staining for HPVs 16/18 in acellular luminal debris in association with squamous metaplasia of the tumor, but staining was negative in the glandular cells of the tumor. Human papillomavirus was not detected by in situ hybridization in the remaining specimen, which was PCR positive for HPV 16. In situ hybridization was weakly positive for HPVs 31/33/35 in one specimen and was weakly positive for HPVs 6/11 in benign endometrial epithelial cells but not in tumor cells of another specimen that tested positive for HPV by L1 PCR. Two dimensional gel electrophoresis performed on two specimens showed that HPV DNAs were integrated into cellular DNA with no episomal coexistence. These findings suggest that HPV, especially HPV 16, may play an etiologic role in a fraction of endometrioid adenocarcinomas. PMID- 7774897 TI - Cocaine induced intracerebral hemorrhage: analysis of predisposing factors and mechanisms causing hemorrhagic strokes. AB - We analyzed 26 autopsy cases of cocaine induced intracerebral hemorrhage and compared those findings with those of 26 autopsy cases of cocaine induced cerebral aneurysm rupture. The incidence of hypertensive cardiovascular disease (HCVD) was significantly higher in persons with intracerebral hemorrhage than in those with aneurysm rupture. Our findings suggest that HCVD predisposes to cocaine induced intracerebral hemorrhage. We propose that the foregoing relationship results from a cocaine induced alteration of cerebral autoregulation in the context of increased cerebral blood flow. PMID- 7774898 TI - Nucleolar organizer regions as markers of endometrial proliferation: a study of normal, hyperplastic, and neoplastic tissue. AB - Nucleolar organizer regions (NORs) are loops of DNA that transcribe to ribosomal RNA. They can be visualized as intranuclear black dots by histochemical staining with a colloid silver solution. We applied this method to 78 sections of endometrial tissue obtained either from curettage or from hysterectomy specimens. The histological diagnoses were as follows: normal proliferative (N = 9) or secretory (N = 5) endometrium, simple hyperplasia (N = 10), complex hyperplasia (N = 18), atypical hyperplasia (N = 8), and adenocarcinoma (N = 28). Mean silver stained NOR (AgNOR) counts per cell were 3.2 (standard error of the mean [SEM], 0.2) in normal proliferative and 2.7 (SEM, 0.2) in normal secretory epithelium, and increased to 4.1 (SEM, 0.3) in simple hyperplasia, to 5.4 (SEM, 0.4) in complex hyperplasia, to 8.1 (SEM, 0.7) in atypical hyperplasia, and finally to 10.0 (SEM, 0.5) in endometrial carcinoma. The differences were significant (one factor analysis of variance [ANOVA], P < .001). A slight increase but no significant difference was seen between the mean AgNOR counts in endometrial carcinomas of different histological grades. Our study suggests that AgNOR counts are reliable markers of endometrial proliferation and allow a clear distinction between benign, premalignant, and malignant epithelial changes. Our AgNOR findings in endometrial hyperplasia support the concept of various degrees of hyperplasia that can be differentiated on morphological grounds. PMID- 7774899 TI - The histological spectrum of pulmonary graft-versus-host disease in bone marrow transplant recipients. AB - The histological changes in 17 biopsy specimens of the lung showing graft-versus host disease (GVHD) in bone marrow transplant (BMT) recipients were reviewed and correlated with the patients' clinical courses. These morphological changes fell into four transplant-related categories: diffuse alveolar damage, lymphocytic bronchitis/bronchiolitis with interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia, and cicatricial bronchiolitis obliterans. Pulmonary disease correlated with the presence of GVHD at extrathoracic sites. Patients with active lymphocytic bronchitis/bronchiolitis, cicatricial bronchiolitis obliterans, and diffuse alveolar damage had particularly poor outcomes. A proposal is offered for the categorization of the pulmonary damage caused by GVHD in BMT recipients. PMID- 7774900 TI - Amplification of human papillomavirus types 16 and 18 in invasive cervical cancer. AB - The distribution and amplification patterns of human papillomavirus were studied in 15 human papillomavirus (HPV) 16- and six HPV18-positive cervical carcinomas by colorimetric in situ hybridization (ISH). The findings were correlated with the viral copy number and status of E1/E2 viral genes in the tumor DNA, as studied by dot blot analysis and the polymerase chain reaction, respectively. The tumors were classified according to the ISH signal into single dot, multidot, diffuse, and mixed patterns. The signal was homogeneously distributed only in single dot tumors and was clearly heterogeneous in tumors with mixed nuclear signal patterns, including both dot and diffuse signals. The single dot pattern predominated in HPV 18-positive tumors (83%), whereas the multidot pattern was most frequent in HPV 16-positive tumors (47%). Diffuse and mixed patterns were noted only in HPV 16-positive tumors (33%). The lowest mean copy of number per cell was observed in single dot tumors (25 +/- 15) with an ascendent trend toward the diffuse signal tumors (2832 +/- 2281). E1/E2 genes were disrupted in 75% of the single/multidot tumors and in none of the diffuse/mixed tumors. These data suggest diffuse signals originate by episomal amplification and dot signals originate by viral integration. Diffuse and dot patterns suggest different mechanisms of viral transformation. PMID- 7774901 TI - Colonic histiocytic neoplasm mimicking malignant histiocytosis and presenting as intussusception. AB - It is now apparent that distinction between the so-called malignant histiocytosis and lymphoma can be made using panels of established immunohistochemical markers and/or genotypic analysis. Many, if not all, of the previously diagnosed cases of malignant histiocytosis have been shown to be of lymphoid, rather than histiocytic, lineage. We report a rare case of colonic histiocytic neoplasm accompanied by a lymphoreticular dissemination that mimicked that of malignant histiocytosis. In addition, barium studies and computed axial tomography confirmed an intussusception that subsequently developed. The histiocytic nature of the neoplastic cells was supported by immunohistochemical, ultrastructural, and cytochemical studies. To our knowledge our case may represent the fifth documented case of a histiocytic malignancy reported in the literature. The relationship among the various cases will be discussed as well as the significance of the focal S-100 immunoreactivity observed in the present case. PMID- 7774902 TI - Acute neutrophilic myositis in Sweet's syndrome: late phase transformation into fibrosing myositis and panniculitis. AB - Early in the course of myeloblastic leukemia a patient concurrently developed febrile neutrophilic dermatosis and sterile acute myositis. The dermatitis and myositis were unresponsive to antibiotic therapy but remitted within a few days of institution of steroid treatment. The patient died of myocardial infarction. At autopsy the dermis was normal. Previously effected muscles were scarred. The overlying fascia and subcutaneous septa were fibrotically thickened. In addition, segmental acute aortitis was detected. Acute myositis and aortitis may reflect further organ manifestations of the Sweet's reactivity pattern. It is proposed that Sweet's myositis and dermatitis may evolve into a fibrosing myositis and panniculitis. PMID- 7774903 TI - Interpretation of artifactual vascular invasion in cervical squamous precursors due to lidocaine injection. PMID- 7774904 TI - Dormant cells in columnar cell carcinoma of the thyroid. PMID- 7774905 TI - The purported link between agent orange and cancer. PMID- 7774906 TI - MATS: a rapid and efficient method for the development of microsatellite markers from YACs. AB - In this report, we describe the successful application of a rapid and efficient procedure, based on subtractive hybridization and PCR amplification, for generating microsatellite-based markers directly from yeast artificial chromosomes (YACs). This strategy, termed MATS (marker addition through subtraction), exploits the fact that the only difference between a yeast host strain harboring a YAC and the host strain alone is the artificial chromosome. Given the low complexity of the yeast genome and relatively large target size presented by a YAC, only a single round of subtraction is required before amplification of the target sequences (YAC) and cloning into a plasmid vector for further analysis. Several key steps have been designed to achieve optimal subtraction and to obtain preferential amplification and recovery of the target sequences. Methods for efficient construction of small insert libraries and rapid, nonradioactive screening have also been integrated into the protocol. Using a 750-kb YAC as a target, we identified a minimum of 14 unique microsatellite containing clones, leading to the development of 12 polymorphic STSs (sequence-tagged sites). These new markers will facilitate the genetic localization of targeted locus and allow the accurate ordering by STS content mapping of a cloned contig spanning the interval. In addition to the utility of this approach in positional cloning, this strategy may provide an approach for filling gaps in the emerging genetic maps. PMID- 7774907 TI - Conservation and evolution of (CT)n/(GA)n microsatellite sequences at orthologous positions in diverse mammalian genomes. AB - The distribution and evolution of (CT)n microsatellites were examined in GenBank mammalian DNA sequences because these microsatellites are known to play important roles in the regulation of some genes in Drosophila melanogaster. A total of 236 (CT)n microsatellite loci were found in GenBank mammalian gene sequences. To determine whether (CT)n microsatellite arrays were conserved at orthologous positions in distantly related mammalian sequences, we determined whether orthologous sequences existed in GenBank for each of the 236 loci. A total of 47 sequence alignments could be made. For rodent x rodent comparisons, 7 of 8 (CT)n arrays were conserved at identical positions in each pair of orthologous sequences. Comparisons of orthologous sequences between different orders of mammals indicated that 11 of 39 (CT)n arrays occurred at orthologous positions or within 1 kb of orthologous positions in each pair of sequences. It appears that there is some level of conservation of (CT)n repeats in distantly related mammals. However, this level of conservation may not be greater than what might be expected to occur by chance. In 13 cases where (CT)n arrays were not conserved at orthologous positions, the lack of a (CT)n array in one sequence resulted from either nucleotide substitution within an array or nonexpansion of a shorter (CT)n element. In these cases, significant sequence identity could be detected throughout the entire region even though the repeat array was not detected in one of the sequences. In contrast, there was a disruption of sequence identity in the (CT)n microsatellite region that ranged from 24 to 1600 bp in 21 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774908 TI - High-resolution cytogenetic mapping of the short arm of chromosome 1 with newly isolated 411 cosmid markers by fluorescence in situ hybridization: the precise order of 18 markers on 1p36.1 on prophase chromosomes and "stretched" DNAs. AB - A high-resolution cytogenetic map of the short arm of chromosome 1 with newly isolated 411 cosmid markers was constructed by fluorescence in situ hybridization (FISH). These markers were scattered throughout chromosome 1p, but they were preferentially concentrated on R-band dominant regions such as 1p36, 1p34, 1p32, 1p22, and 1p13. Among these markers, 197 were localized on chromosome band 1p36, a region frequently deleted in neuroblastoma. Of these, 18 were precisely ordered on 1p36.1 by multicolor FISH of prophase chromosomes and "stretched" DNAs as follows: 1pter-163-41-11-1-226-586-568-614-631-665-451-199-190-561-241-74-1 76 652-1cen. The high-density map of chromosome 1p constructed here can provide useful landmarks for constructing a contig map of the short arm of chromosome 1 with YACs and cosmid clones and will expedite the identification of breakpoints and/or tumor suppressor gene(s) associated with several types of malignant tumors that frequently exhibit chromosomal aberrations or deletions of chromosome 1p. PMID- 7774909 TI - Regional assignment by hybrid mapping of 36 expressed sequence tags (ESTs) on human chromosome 6. AB - We have determined the regional chromosome assignment of 36 cDNAs from infant brain libraries by assessing the concordant segregation of PCR products using a human-rodent hybrid mapping panel that subdivides chromosome 6 into 15 regions. These mapped sequences serve as markers for the physical and expression maps of chromosome 6, as well as candidate genes for various disease loci. Sequence analysis has identified putative functions and motifs for some of these genes. PMID- 7774911 TI - Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse. AB - We have set out to produce a comprehensive comparative map between human chromosome 9 (HSA9) and the laboratory mouse. The mouse homologues of 50 loci that were known to map to HSA9 were mapped by interspecific backcross linkage analysis. Ten loci from the short arm of HSA9 were mapped, and 40 from HSA9q, with 24 markers coming from the HSA9q33-q34 region--a part of the chromosome known to be very gene rich. Fifteen new assignments have been made--Ak3, Ctsl, Cntfr, C8g, D2H9S46E, Eng, Gcnt1, Irebp, Pappa, Ptgds, Snf212, Tal2, Tmod, Vav2, and Vldlr, the human homologues of which all map to HSA9. In addition, the assignment of Snf212 and Vldlr to MMU19 has defined a new region of synteny between the proximal portion of the short arm of HSA9 and the mouse. PMID- 7774910 TI - Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. AB - The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previously assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detected in 14 primary acute leukemia or myelodysplasia samples with structural abnormalities of chromosome 20q11, the gene was amplified and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb. PMID- 7774912 TI - Relative size and evolution of the germline repertoire of T-cell receptor beta chain gene segments in nonhuman primates. AB - The mammalian T-cell receptor (TCR) gene complexes exist as multiple tandemly arrayed gene segments that have apparently arisen by gene duplication mechanisms. A study of the number of TCR germline gene segments in several primate species might provide insight into the relative rate and patterns of gene duplication and deletion within these gene complexes. DNA probes from the TCR beta-chain variable (TCRBV) region gene segment subfamilies 1 through 25 and the constant region gene segment were sequentially hybridized under low stringency to Southern blots containing genomic DNA of human, gorilla, orangutan, and pig-tailed macaque. The number of gene members in each subfamily was estimated from the number of hybridizing DNA fragments. The results show apparent examples of both TCRB V gene duplication and deletion since speciation of the Hominoids from Cercopithecoid (Old World) primates. For one putative duplication/deletion event involving six TCRBV gene segments, derivation and comparison of germline DNA sequence from macaque and human as well as Southern blot analysis of additional primates demonstrated that this event was a duplication that occurred after the divergence of the family Pongidae (Greater Apes) from Hylobatidae (Lesser Apes). Southern blot analysis of multiple pig-tailed macaques and their offspring suggests a degree of DNA sequence variability in these gene segments similar to that observed in humans. An appreciation of the size and variability of each TCRBV subfamily will be useful when considering the DNA primers and probes necessary to measure the relative usage of these TCRBV genes as part of the immune response in these nonhuman primates. PMID- 7774913 TI - Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor. AB - Ciliary neurotrophic factor (CNTF) has recently been found to share receptor components with, and to be structurally related to, a family of broadly acting cytokines, including interleukin-6, leukemia inhibitory factor, and oncostatin M. However, the CNTF receptor complex also includes a CNTF-specific component known as CNTF receptor alpha (CNTFR alpha). Here we describe the molecular cloning of the human and mouse genes encoding CNTFR. We report that the human and mouse genes have an identical intron-exon structure that correlates well with the domain structure of CNTFR alpha. That is, the signal peptide and the immunoglobulin-like domain are each encoded by single exons, the cytokine receptor-like domain is distributed among 4 exons, and the C-terminal glycosyl phosphatidylinositol recognition domain is encoded by the final coding exon. The position of the introns within the cytokine receptor-like domain corresponds to those found in other members of the cytokine receptor superfamily. Confirming a recent study using radiation hybrids, we have also mapped the human CNTFR gene to chromosome band 9p13 and the mouse gene to a syntenic region of chromosome 4. PMID- 7774914 TI - A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III. AB - 4-Hydroxyphenylpyruvic acid dioxygenase (HPD; EC 1.13.11.27) is an important enzyme in tyrosine catabolism in most organisms. Decreased activity of 4 hydroxyphenylpyruvic acid dioxygenase in the liver of mouse strain III is associated with tyrosinemia. We report a nucleotide substitution that generates a termination codon in exon 7 of the 4-hydroxyphenylpyruvic acid dioxygenase gene in III mice. This mutation is associated with partial exon skipping, and most of the mRNA lacks sequences corresponding to exon 7. The partial exon skipping apparently is the result of a nonsense mutation in the exon. Mouse strain III is a model for human tyrosinemia type 3 (McKusick 276710), and this strain together with recently established models for tyrosinemia type 1 will facilitate studies of hereditary tyrosinemias. PMID- 7774915 TI - A human chromosome 7 yeast artificial chromosome (YAC) resource: construction, characterization, and screening. AB - The paradigm of sequence-tagged site (STS)-content mapping involves the systematic assignment of STSs to individual cloned DNA segments. To date, yeast artificial chromosomes (YACs) represent the most commonly employed cloning system for constructing STS maps of large genomic intervals, such as whole human chromosomes. For developing a complete YAC-based STS-content map of human chromosome 7, we wished to utilize a limited set of YAC clones that were highly enriched for chromosome 7 DNA. Toward that end, we have assembled a human chromosome 7 YAC resource that consists of three major components: (1) a newly constructed library derived from a human-hamster hybrid cell line containing chromosome 7 as its only human DNA; (2) a chromosome 7-enriched sublibrary derived from the CEPH mega-YAC collection by Alu-polymerase chain reaction (Alu PCR)-based hybridization; and (3) a set of YACs isolated from several total genomic libraries by screening for > 125 chromosome 7 STSs. In particular, the hybrid cell line-derived YACs, which comprise the majority of the clones in the resource, have a relatively low chimera frequency (10-20%) based on mapping isolated insert ends to panels of human-hamster hybrid cell lines and analyzing individual clones by fluorescence in situ hybridization. An efficient strategy for polymerase chain reaction (PCR)-based screening of this YAC resource, which totals 4190 clones, has been developed and utilized to identify corresponding YACs for > 600 STSs. The results of this initial screening effort indicate that the human chromosome 7 YAC resource provides an average of 6.9 positive clones per STS, a level of redundancy that should support the assembly of large YAC contigs and the construction of a high-resolution STS-content map of the chromosome. PMID- 7774916 TI - A boundary of long-range G + C% mosaic domains in the human MHC locus: pseudoautosomal boundary-like sequence exists near the boundary. AB - The human genome is composed of long-range G+C% (GC%) mosaic structures related to chromosome bands. We found the human MHC locus to be an example of megabase level GC% mosaic structures and predicted a possible boundary of the megabase level domains within an undercharacterized 450-kb region harboring the junction of MHC classes II and III. Chromosome walking of the 450-kb region and base compositional analysis precisely located the boundary of the mosaic domains, disclosing a sharp GC% transition. Near the transition point there was a 20-kb dense Alu cluster, a 30-kb dense LINE-1 cluster, and a sequence highly homologous with the pseudoautosomal boundary of the short arms of human sex chromosomes (PAB1X and PAB1Y); PAB1X and PAB1Y are the interface between sex-specific and pseudoautosomal regions. Many PAB1XY-like sequences (PABLs) were detected by hybridization against genomic DNA, and the new sequences defined the complete form of PABLs to be about 650 nt. PMID- 7774917 TI - YAC contigs covering an 8-megabase region of 3p deleted in the small-cell lung cancer cell line U2020. AB - Somatic deletions of chromosome 3p occur at high frequencies in cancers of kidney, breast, cervix, head and neck, nasopharynx, and lung. The frequency of 3p deletion in lung cancer approaches 100% among small cell lesions and 70 to 80% in non-small cell lesions. This evidence strongly implies that one or more tumor suppressor genes of potentially widespread significance reside within the deleted region(s). Precise definition of the deleted target region(s) has been difficult due to the extensive area(s) lost and use of markers with low informativeness. However, improved definition remains essential to permit isolation of putative tumor suppressor genes from 3p. The identification of several small, homozygous 3p deletions in lung cancer cell lines has provided a critical resource that will assist this search. The U2020 cell line contains a small homozygous deletion that maps to a very proximal region of 3p and includes the marker D3S3. We previously identified a subset of DNA markers located within the deleted region and determined their relative order by pulsed-field gel mapping studies. In the present report, we describe the development of YAC contigs that span the majority of the deleted region and link up to flanking markers on both sides. The centromere proximal portion of the contig crosses the breakpoint from an X;3 translocation located within 3p12 providing both location and orientation to the map. PCR-based (CA)n microsatellite polymorphisms have been localized within and flanking the deletion region. These markers should greatly facilitate loss-of heterozygosity studies of this region in human cancer. The contig provides a direct means for isolation of putative tumor suppressor genes from this segment of 3p. PMID- 7774918 TI - Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa. AB - Laminin 5 consists of three polypeptides, alpha 3, beta 3, and gamma 2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMB3 gene. Characterization of five overlapping lambda phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 bp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. PMID- 7774919 TI - The human and mouse homologs of the yeast RAD52 gene: cDNA cloning, sequence analysis, assignment to human chromosome 12p12.2-p13, and mRNA expression in mouse tissues. AB - The yeast Saccharomyces cerevisiae RAD52 gene is involved in DNA double-strand break repair and mitotic/meiotic recombination. The N-terminal amino acid sequence of yeast S. cerevisiae, Schizosaccharomyces pombe, and Kluyveromyces lactis and chicken is highly conserved. Using the technology of mixed oligonucleotide primed amplification of cDNA (MOPAC), two mouse RAD52 homologous cDNA fragments were amplified and sequenced. Subsequently, we have cloned the cDNA of the human and mouse homologs of yeast RAD52 gene by screening cDNA libraries using the identified mouse cDNA fragments. Sequence analysis of cDNA derived amino acid revealed a highly conserved N-terminus among human, mouse, chicken, and yeast RAD52 genes. The human RAD52 gene was assigned to chromosome 12p12.2-p13 by fluorescence in situ hybridization, R-banding, and DNA analysis of somatic cell hybrids. Unlike chicken RAD52 and mouse RAD51, no significant difference in mouse RAD52 mRNA level was found among mouse heart, brain, spleen, lung, liver, skeletal muscle, kidney, and testis. In addition to an approximately 1.9-kb RAD52 mRNA band that is present in all of the tested tissues, an extra mRNA species of approximately 0.85 kb was detectable in mouse testis. PMID- 7774920 TI - Genetic mapping of the mouse neuromuscular mutation kyphoscoliosis. AB - The ky mouse mutant, kyphoscoliosis, exhibits a degenerative muscle disease resulting in chronic deformation of the spinal column. Using an interspecific backcross segregating the ky mutation, we have mapped the ky locus to a small region of mouse chromosome 9. ky is nonrecombinant with the microsatellites D9Mit24 and D9Mit169 and lies in a conserved linkage group that encompasses human chromosome 3. s-Laminin (LAMS) and the gene for dystrophin-associated glycoprotein 1 (DAG1), which map to human chromosome 3, are both recombinant with ky, ruling them out as candidates. PMID- 7774921 TI - Conservation of the T-box gene family from Mus musculus to Caenorhabditis elegans. AB - Recently, a novel family of genes with a region of homology to the mouse T locus, which is known to play a crucial, and conserved, role in vertebrate development, has been discovered. The region of homology has been named the T-box. The T-box domain of the prototypical T locus product is associated with sequence-specific DNA binding activity. In this report, we have characterized four members of the T box gene family from the nematode Caenorhabditis elegans. All lie in close proximity to each other in the middle of chromosome III. Homology analysis among all completely sequenced T-box products indicates a larger size for the conserved T-box domain (166 to 203 residues) than previously reported. Phylogenetic analysis suggests that one C. elegans T-box gene may be a direct ortholog of the mouse Tbx2 and Drosophila omb genes. The accumulated data demonstrate the ancient nature of the T-box gene family and suggest the existence of at least three separate T-box-containing genes in a common early metazoan ancestor to nematodes and vertebrates. PMID- 7774922 TI - Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human. AB - We recently purified and cloned the gene for a DNA structure-specific endonuclease, FEN-1, from murine cells. The murine protein recognizes 5' DNA flap structures that have been proposed in DNA replication, repair, and recombination. Here, we report the sequence of the human FEN1 gene. The translated sequence is identical to peptide sequence obtained from maturation factor-1, which is 1 of the 10 essential proteins for cell-free DNA replication. The human protein has the same structure-specific DNA endonuclease activity as the murine protein. Two human chromosomal hybridization signals, 11q12 and 1p22.2, were observed by FISH analysis using human genomic clones homologous to the mouse Fen-1 gene. The localization on human 11q12 was confirmed using radiation-reduced hybrids. The mouse Fen-1 gene is assigned to chromosome 19 based on somatic cell hybrids. The significance of these FEN1 gene localizations in human and mouse is discussed. PMID- 7774923 TI - Cloning mammary cell cDNAs from 17q12-q23 using interspecific somatic cell hybrids and subtractive hybridization. AB - We have cloned human genes that are encoded in the region 17q12-q23 and expressed in breast tissue using interspecific somatic cell hybrids and subtractive hybridization. Two mouse microcell hybrids containing fragments of human chromosome 17 with a nonoverlap region at 17q12-q23 were generated by microcell transfer. Radiolabeled cDNA was synthesized from the hybrid cell containing the 17q12-q23 interval and was subtracted with an excess of RNA from the hybrid cell lacking the interval. Resulting cDNA probes enriched for sequences from 17q12-q23 were used to screen a human premenopausal breast cDNA library, and 60 cDNAs were identified. Three of these cDNAs mapped to the hybrid cell nonoverlap region. These cDNAs were expressed in mammary epithelial cell hybrids, although none appeared to be breast-specific. Sequence analysis of the cDNAs revealed that clone 93A represents a previously unidentified gene, clone 98C has homology to an expressed sequence tag from goat mammary tissue, and clone 200A is identical to the human homologue of the Drosophila melanogaster flightless-I gene. These genes map outside a 1-cM region linked to early onset familial breast cancer but may be useful genetic markers in the 17q12-q23 region. PMID- 7774924 TI - Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17. AB - We have used a combination of methods (exon amplification, direct selection, direct screening, evolutionary conservation, island rescue-PCR, and direct sequence analysis) to survey approximately 600 kb of genomic DNA surrounding the BRCA1 gene for transcribed sequences. We have cloned a set of fragments representing at least 26 genes. The DNA sequence of these clones reveals that 5 are previously cloned genes; the precise chromosomal location of 2 was previously unknown, and 3 have been cloned and mapped by others to this interval. Three other genes, including BRCA1 itself, have recently been mapped independently to this region. Sequences from 11 genes are similar but not identical matches to known genes; 5 of these appear to be the human homologues of genes cloned from other species. Another 7 genes have no similarity with known genes. In addition, 39 putative exons and 14 expressed sequence tags have been identified and mapped to individual cosmids. This transcript map provides a detailed description of gene organization for this region of the genome. PMID- 7774925 TI - Direct selection of expressed sequences within a 1-Mb region flanking BRCA1 on human chromosome 17q21. AB - Direct selection of genes within the interval of chromosome 17q21 containing BRCA1 was performed. YAC and cosmid contigs spanning the BRCA1 region were used to select cDNA clones from pools of cDNAs derived from human placenta, HeLa cells, activated T cells, and fetal head. A minimum set of 48 fragments of nonoverlapping cDNAs that unequivocally mapped within a 1-Mb region was identified, although it is not yet known how many of these are derived from the same transcript. DNA sequence analyses revealed that 4 of these cDNAs were derived from known genes (EDH17B2, glucose-6-phosphatase, IAI.3B, and E1AF), 1 is a member of a previously described gene family (HMG-17), and 7 share substantial identity with previously described genes from human or other species. The remainder showed no significant homology to known genes. Limited PCR-based expression profiles of a set of 13 of the genes were performed, and all gave positive results with at least some cDNA sources supporting the contention that they truly represent transcribed sequences. A comparison between genes obtained from this region by direct selection with those obtained by direct screening or exon trapping (see accompanying papers, this issue) revealed that over 90% of the genes identified by exon trapping were represented in the selected material and that at least two additional genes that appear to represent low abundance transcripts with restricted expression profiles were identified by selection but not by other means. PMID- 7774926 TI - 22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors. AB - In our effort to identify BRCA1, 22 genes were cloned from a 1-Mb region of chromosome 17q21 defined by meiotic recombinants in families with inherited breast and/or ovarian cancer. Subsequent discovery of another meiotic recombinant narrowed the region to approximately 650 kb. Genes were cloned from fibroblast and ovarian cDNA libraries by direct screening with YACs and cosmids. The more than 400 cDNA clones so identified were mapped to cosmids, YACs, and P1 clones and to a chromosome 17 somatic panel informative for the BRCA1 region. Clones that mapped back to the region were hybridized to each other and consolidated into clusters reflecting 22 genes. Ten genes were known human genes, 5 were human homologs of known genes, and 7 were novel. Each gene was sequenced, compared to genes in the databases to find homologies, and analyzed for mutations in BRCA1 linked families and tumors. Eight mutations were found in tumors or families and not in controls. In the gene encoding alpha-N-acetylglucosaminidase, approximately 100 kb proximal to the 650-kb linked region, somatic nonsense, missense, and splice junction mutations occurred in 3 breast tumors, but not in these patients' germline DNA nor in controls. In an ets-related oncogene in the linked region, a missense mutation cosegregated with breast cancer in one family and was not observed in controls. In a human homolog of a yeast pre-mRNA splicing factor, 3 different mutations cosegregated with breast cancer in 3 families and were not observed in controls. In these and the other genes in the region, 36 polymorphic variants were observed in both cases and controls. PMID- 7774927 TI - A YAC-, P1-, and cosmid-based physical map of the BRCA1 region on chromosome 17q21. AB - A familial early-onset breast cancer gene (BRCA1) has been localized to chromosome 17q21. To characterize this region and to aid in the identification of the BRCA1 gene, a physical map of a region of 1.0-1.5 Mb between the EDH17B1 and the PPY loci on chromosome 17q21 was generated. The physical map is composed of a yeast artificial chromosome (YAC) and P1 phage contig with one gap. The majority of the interval has also been converted to a cosmid contig. Twenty-three PCR based sequence-tagged sites (STSs) were mapped to these contigs, thereby confirming the order and overlap of individual clones. This complex physical map of the BRCA1 region was used to isolate genes by a number of gene identification techniques and to generate transcript maps of the region, as presented in the three accompanying manuscripts of Brody et al. (1995), Osborne-Lawrence et al. (1995), and Friedman et al. (1995). PMID- 7774928 TI - Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2 q24.3, 3q27, 13q12.3-q13, and 7q11.23. AB - Replication factor C is a multimeric primer-recognition protein consisting of five subunits (p145, p40, p38, p37, and p36.5) and is essential for the processive elongation of DNA chains catalyzed by DNA polymerase delta or epsilon in human cells. We have mapped the locations on human chromosomes of the genes coding for the four smaller subunits [p36.5 (RFC5), p37 (RFC4), p38 (RFC3), and p40 (RFC2)] using both PCR amplification from DNAs of a panel of somatic hybrids and fluorescence in situ hybridization to bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23, respectively. PMID- 7774929 TI - Genetic and physical mapping of five novel microsatellite markers on human Xp21.1 p11.22. AB - Five polymorphic CA-dinucleotide repeats, identified in cosmids from the short arm of the human X chromosome, have been characterized and localized to Xp21.1 (DXS572), Xp11.4 (DXS556, DXS574), and Xp11.22-p11.23 (DXS722, DXS573). Genetic mapping with respect to five reference markers that include the gene for CGD (CYBB in Xp21.1), complemented by physical mapping information, has indicated the order tel-DXS572-CYBB-DXS1110-DXS556-DXS574-D XS7-DXS426-DXS722-DXS573-DXS255 cen. PMID- 7774930 TI - Genomic organization and genetic mapping of the neuroimmune gene I2rf5 to mouse chromosome 4. AB - The nervous and immune systems share many functional and molecular similarities, including shared surface antigens, secretions of soluble factors, and cross modulatory effects. We have identified previously a novel mRNA termed F5, which is expressed only in activated T lymphocytes and mature, postmitotic neurons. Tissue specificity and sequence conservation suggest an important function for F5 in T-lymphocyte proliferation and neuronal maturation. The F5 gene product is an evolutionarily conserved, cytoskeletal-associated phosphoprotein. A full-length mouse genomic clone has been isolated. The protein coding region of the F5 gene is approximately 16 kb in length and is composed of 13 coding exons. The gene encoding F5, termed I2rf5, was mapped using interspecies mouse crosses in close proximity to a number of genes associated with neuronal defects on distal chromosome 4. PMID- 7774931 TI - Physical and genetic localization of a Shab subfamily potassium channel (KCNB1) gene to chromosomal region 20q13.2. AB - A human delayed rectifier K+ channel gene has been localized to the long arm of human chromosome 20q13.2 by fluorescence in situ hybridization of genomic P1 clones from this locus. A polymorphic (GA) microsatellite repeat was identified in one of the P1 clones. The new SSR marker (D20S436) was genotyped in four CEPH pedigrees. Two-point linkage analysis indicated linkage of this marker to a PCR marker, D20S109, with a maximum lod score of 9.32 at theta = 0.001. The assignment of this K+ channel gene to 20q13.2 eliminates it as a candidate for the gene associated with benign familial neonatal convulsions (BFNC), which has been localized to 20q13.3. Genetically, the K+ channel gene maps more than 30 cM proximal to the BFNC locus. PMID- 7774932 TI - Mapping of the human cone transducin alpha-subunit (GNAT2) gene to 1p13 and negative mutation analysis in patients with Stargardt disease. AB - We report localization of the human cone transducin (GNAT2) gene using fluorescence in situ hybridization on chromosome 1 in band p13. The recent assignment of a gene for Stargardt disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. We investigated 66 unrelated patients for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. No disease-specific mutations were found, indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt disease. PMID- 7774933 TI - Phospholipase C gamma-2 (Plcg2) and phospholipase C gamma-1 (Plcg1) map to distinct regions in the human and mouse genomes. AB - The phospholipase C gamma-2 (Plcg2) gene encodes an enzyme that plays a crucial role in intracellular signal transduction pathways. This enzyme is important because of its role in the generation of second messengers following the hydrolysis of phosphatidylinositol 4,5-bisphosphate. We have now determined the chromosomal location of this gene in the mouse and human genomes. An interspecific backcross involving AEJ/Gn and Mus spretus mice was used to localize the gene in mouse. A rodent/human somatic cell hybrid panel was used to map PLCG2 in the human genome. Our results position Plcg2 in the central region of mouse chromosome 8. We also show that PLCG2 maps to the long arm of human chromosome 16, in the region q22-qter. Plcg2 does not map near its most closely related family member, Plcg1, in either genome, indicating that the mammalian Plcg genes belong to a dispersed family. PMID- 7774934 TI - The mouse Fau gene: genomic structure, chromosomal localization, and characterization of two retropseudogenes. AB - The Fau gene is the cellular homolog of the fox sequence of the Finkel-Biskis Reilly murine sarcoma virus (FBR-MuSV). FBR-MuSV acquired the Fau gene by transduction in a transcriptional orientation opposite to that of the genomic Fau gene. The genomic structure of the mouse Fau gene (MMFAU) and its upstream elements have been determined and are similar to those of the human FAU gene. The gene consists of five exons and is located on chromosome 19. The first exon is not translated. The promoter region has no well-defined TATA box but contains the polypyrimidine initiator flanked by regions of high GC content (65%) and shows all of the characteristics of a housekeeping gene. The 5' end of the mRNA transcript was determined by 5' RACE analysis and is located, as expected, in the polypyrimidine initiator site. Furthermore, the sequences of two retropseudogenes (Fau-ps1 and Fau-ps2) are reported. Both pseudogenes are approximately 75% identical to the Fau cDNA, but both are shorter due to a deletion at the 5' end and do not encode a functional protein. Fau-prs is interrupted by an AG-rich region of about 350 bp within the S30 region of the Fau cDNA. Fau-ps1 was localized on chromosome 1 and Fau-ps2 on chromosome 7. PMID- 7774935 TI - A physical map encompassing GP2B, EPB3, D17S183, D17S78, D17S1183, and D17S1184. AB - The q21 region of chromosome 17 contains the gene BRCA1, which is involved in familial early-onset breast and ovarian cancers. A physical map of a region that extends from a distal boundary of the BRCA1 region, D17S78, to GP2B has been constructed. The map consists of 30 STSs, including 2 new short tandem repeat polymorphic markers. The contig is composed of a mixture of 7 YACs, 5 P1 plasmids, and 14 cosmids and was ordered by STS-content mapping. PMID- 7774936 TI - The structural genes, MEP1A and MEP1B, for the alpha and beta subunits of the metalloendopeptidase meprin map to human chromosomes 6p and 18q, respectively. AB - Meprins are cell membrane, oligomeric metalloendopeptidases composed of two distinct but evolutionarily related subunits, alpha and beta. The structural genes for the meprin subunits, Mep-1 alpha and Mep-1 beta, have been previously mapped to chromosomes 17 and 18, respectively, of the mouse genome. We now report the localization of MEP1A and MEP1B in the human genome. MEP1A mapped to the short arm of chromosome 6 by the use of radiation and somatic cell hybrids. More specifically, it is localized between the centromere and GSTA2 in 6p11-p12. MEP1B mapped to chromosome 18, by the use of somatic cell hybrids, in 18q12.2-q12.3, proximal to the TTR/PALB gene. As in the mouse genome, the two homologous human structural genes for alpha and beta (50% identical on the cDNA level) are unlinked. These new markers on human chromosomes 6 and 18 extend the region of known linkage homology with mouse chromosomes 17 and 18, respectively, and provide new molecular access to regions of the human genome. PMID- 7774937 TI - Physical analysis of the tuberous sclerosis region in 9q34. AB - We report the construction of a physical map based on cloned DNA within the candidate region for the tuberous sclerosis complex (TSC1) gene on chromosome 9q34, between the markers D9S149 and D9S66. The DNA clones form three contigs consisting of 7 YACs, bridged by P1 and cosmid clones, and cover more than 950 kb of 9q34. Despite intensive screening of all available libraries, two gaps remain. A detailed physical map of much of this region was derived, and restriction mapping of the YAC, P1, and cosmid clones reveals novel CpG islands in this region. This set of genomic clones provides a resource for characterizing candidates for the TSC1 gene, guided by the location of CpG islands. PMID- 7774938 TI - Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C. AB - The mouse receptor tyrosine kinase (RTK) NEP, also called Ptk-3, is widely expressed, with high levels in proliferating neuroepithelia of mouse embryos. The recently described human discoidin domain receptor (DDR) has a predicted amino acid sequence 93% identical to that of murine NEP and may be its human homologue. We have mapped the gene encoding NEP in human and mouse by fluorescence in situ hybridization using a mouse cDNA probe. The NEP/Nep gene maps to human chromosome 6p21.3 and mouse chromosome 17C, respectively. This places the NEP/Nep gene at, or near, the major histocompatibility (MHC) locus--HLA in human and H2 in mouse, respectively. Based on its pattern of expression during development, NEP and Nep represent candidate genes for several MHC-linked developmental abnormalities in human and mouse. PMID- 7774939 TI - Structure of the mouse H2A.X gene and physical linkage to the UPS locus on chromosome 9: assignment of the human H2A.X gene to 11q23 by sequence analysis. AB - The H2A.X gene was cloned from the C3H mouse strain, and its structure was determined. Sequence analysis revealed that this gene is situated in close proximity to the porphobilinogen deaminase (PBGD) gene in the opposite orientation. The synteny is conserved in human. This permits us to assign the H2A.X gene to chromosome 9 and 11q23 in mouse and human, respectively. PMID- 7774940 TI - Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3. AB - Transport proteins have essential functions in the uptake of neurotransmitters and neuromodulators. We have mapped the gene encoding the taurine transporter, Taut, to the central region of mouse chromosome 6. Analysis of a cross segregating the neurological mutant mnd2 excluded Taut as a candidate gene for this closely linked mutation. To map the human taurine transporter gene, TAUT, a sequence-tagged site (STS) corresponding to the 3' untranslated region of the human cDNA was developed. TAUT was assigned to human chromosome 3 by typing this STS on a panel of somatic cell hybrids. Further analysis of a hybrid panel containing defined deletions of chromosome 3 suggested that TAUT maps to 3p21 p25. These data extend a conserved linkage group on mouse chromosome 6 and human chromosome 3p. Deletion of TAUT might contribute to some phenotypic features of the 3p- syndrome. PMID- 7774941 TI - CEPH viewer: a client-server database to browse and manipulate CEPH physical mapping and linkage data. PMID- 7774942 TI - Assignment of the Waldner blood group locus (WD) to 17q12-q21. PMID- 7774944 TI - Assignment of ALDH3 to human chromosome 17p11.2 and ALDH5 to human chromosome 9p13. PMID- 7774943 TI - A novel C2H2 zinc-finger protein gene (ZNF160) maps to human chromosome 19q13.3 q13.4. PMID- 7774946 TI - Assignment of the human glypican gene (GPC1) to 2q35-q37 by fluorescence in situ hybridization. PMID- 7774947 TI - Integration of the 1993-94 Genethon genetic linkage map for chromosome 18 with the physical map using a somatic cell hybrid mapping panel. PMID- 7774945 TI - Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3). PMID- 7774948 TI - Assignment of the human genes for desmocollin 3 (DSC3) and desmocollin 4 (DSC4) to chromosome 18q12. PMID- 7774949 TI - Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD. PMID- 7774950 TI - Assignment of the gene (EPLG2) encoding a high-affinity binding protein for the receptor tyrosine kinase elk to a 200-kilobasepair region in human chromosome Xq12. PMID- 7774952 TI - Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization. PMID- 7774951 TI - The gene for fibroblast activation protein alpha (FAP), a putative cell surface bound serine protease expressed in cancer stroma and wound healing, maps to chromosome band 2q23. PMID- 7774953 TI - The mouse homologue of the tuberin gene (TSC2) maps to a conserved synteny group between mouse chromosome 17 and human 16p13.3. PMID- 7774954 TI - Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. AB - The ubiquitously expressed upstream stimulatory factor (USF) involved in the transcription of a wide variety of cellular genes is defined as dimers of c-myc related proteins, composed of a basic helix-loop-helix/leucine zipper region. The USF family consists of different members that split into two groups: MLTF or USF1 and USF2 or FIP. We present here evidence that USF1 and USF2 are distinct closely related genes in human, rat, and mouse. Based on the recent cloning of rat and human new cDNAs, we have isolated genomic clones encompassing the murine USF2 gene, which consists of at least 10 exons spanning a minimum of 10 kb of genomic DNA. Unexpectedly, the organization of USF2 appears very split up by introns (0.08 to over 6 kb in size), compared to the myc gene structure. The entire gene (but the larger intron) and 1.6 kb of the 5' flanking region were sequenced. This 5' flanking region is GC-rich, contains several putative transcription binding sites, and has no apparent TATA box. Gene mapping of murine USF2 and USF1 has been determined by in situ hybridization, indicating the localization of USF2 on chromosome 7 and of USF1 on chromosomes 1 and 11. PMID- 7774955 TI - The CEPH consortium linkage map of human chromosome 16. AB - A Centre d'Etude du Polymorphisme Humain (CEPH) consortium map of human chromosome 16 has been constructed. The map contains 158 loci defined by 191 different probe/restriction enzyme combinations or primer pairs. The marker genotypes, contributed by 9 collaborating laboratories, originated from the CEPH families DNA. A total of 60 loci, with an average heterozygosity of 68%, have been placed on the framework genetic map. The genetic map contains 7 genes. The length of the sex-averaged map is 165 cM, with a mean genetic distance between loci of 2.8 cM; the median distance between markers is 2.0 cM. The male map length is 136 cM, and the female map length is 197 cM. The map covers virtually the entire chromosome, from D16S85, within 170 to 430 kb of the 16p telomere, to D16S303 at 16qter. The markers included in the linkage map have been physically mapped on a partial human chromosome 16 somatic cell hybrid panel, thus anchoring the genetic map to the cytogenetic-based physical map. PMID- 7774956 TI - A 500-kilobase region containing the tuberous sclerosis locus (TSC1) in a 1.7 megabase YAC and cosmid contig. AB - A complete overlapping clone map of a 1.7-Mb region from DBH to D9S67 that includes the TSC1 candidate region has been constructed. The map includes YAC and cosmid clones, contains STS approximately every 50 kb on average, and establishes the order of five previously unordered loci. The overall physical length of this segment of chromosome 9q34 (1.7 Mb) is significantly less than expected compared to its estimated genetic length (approximately 10 cM). Consequently, the physical length of the TSC1 candidate region is substantially less than predicted by a genetic distance of approximately 2 cM. PMID- 7774957 TI - Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1). AB - Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences (Tarbp2-rs1, Tarbp2-rs2). The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells. PMID- 7774958 TI - Cosmid assembly and anchoring to human chromosome 21. AB - A human chromosome 21-specific cosmid library from the Lawrence Livermore National Laboratory has been analyzed by two complementary methods, fingerprinting and hybridization; 40% coverage of the entire chromosome 21 has been achieved. To prepare a contig pool, approximately 9300 cosmid clones randomly selected from the library were fingerprinted and automatically assembled into 467 overlapping sets by the fluorescence-tagged restriction fragment method. The average size of the overlapping sets was 9.5 cosmids with minimal tiling paths consisting of 5.4 cosmids with a 10-kb extension each. However, as many as 10% of overlaps within members were estimated to be false. For regional localization, we hybridized gridded arrays of cosmids with inter-Alu-PCR probes obtained from YAC clones and somatic cell hybrids and assigned 592 cosmids to 26 subregions of 21q. Of these, 371 clones were incorporated into 139 contigs, anchoring the total 1864 cosmids to the subregion. The remaining 221 clones were mapped as orphans. To correlate the cytogenetic, YAC, and cosmid maps on 21q, the translocation breakpoints of the chromosomes contained in the somatic cell hybrids were mapped with respect to the STS content of the YACs. From the gene cluster regions, 176 ribosomal and 25 alphoid clones were isolated by hybridization. Together, these sets of anchored contigs and cosmids will provide a valuable resource for construction of a high-resolution map and for isolation of genes of interest from chromosome 21. PMID- 7774959 TI - Genomic organization of the mouse cyclin D1 gene (Cyl-1). AB - To determine the genomic organization of the mouse cyclin D1 locus (Cyl-1), a series of cosmids and cDNAs were recovered by hybridization with a genomic probe representing the 5' end of the homologous human gene, CCND1. Primer extension indicated that transcripts originate from one of three adjacent nucleotides at a single start site. Two overlapping cDNA clones that essentially accounted for the complete sequence of the larger 4.0-kb Cyl-1 transcript were characterized. A combination of RNase protection and sequencing across intron-exon boundaries established that the gene is organized into five coding exons with a long 3' untranslated region. Repeated attempts to isolate clones corresponding to the minor 3.5-kb RNA were compromised by the presence of an internal poly(A) domain. However, hybridization with specific probes revealed that the minor transcript lacks approximately 800 nucleotides from the 3' end of the major transcript and may be generated by a novel mechanism or by RNA processing. PMID- 7774960 TI - Genomic organization of the neurofibromatosis 1 gene (NF1). AB - Neurofibromatosis 1 maps to chromosome band 17q11.2, and the NF1 locus has been partially characterized. Even though the full-length NF1 cDNA has been sequenced, the complete genomic structure of the NF1 gene has not been elucidated. The 5' end of NF1 is embedded in a CpG island containing a NotI restriction site, and the remainder of the gene lies in the adjacent 350-kb NotI fragment. In our efforts to develop a comprehensive screen for NF1 mutations, we have isolated genomic DNA clones that together harbor the entire NF1 cDNA sequence. We have identified all intron-exon boundaries of the coding region and established that it is composed of 59 exons. Furthermore, we have defined the 3'-untranslated region (3'-UTR) of the NF1 gene; it spans approximately 3.5 kb of genomic DNA sequence and is continuous with the stop codon. Oligonucleotide primer pairs synthesized from exon-flanking DNA sequences were used in the polymerase chain reaction with cloned, chromosome 17-specific genomic DNA as template to amplify NF1 exons 1 through 27b and the exon containing the 3'-UTR separately. This information should be useful for implementing a comprehensive NF1 mutation screen using genomic DNA as template. PMID- 7774962 TI - Allergic bronchopulmonary aspergillosis: an emerging disease in India. PMID- 7774961 TI - Genomic organization of the human alpha-adducin gene and its alternately spliced isoforms. AB - The cDNA for the human alpha-adducin gene has been cloned, and different alternately spliced forms have been identified. We report the complete genomic organization of the human alpha-adducin gene and these alternately spliced forms. The human alpha-adducin gene, spanning approximately 85 kb, consists of 16 exons ranging in size from 34 to 1892 bp. One of the spliced forms of the human alpha adducin gene results from alternate use of the 5' splice donor site for exon 10, while another results in a truncated protein following insertion of 34 bp comprising exon 15, followed by a premature stop codon. This alternate spliced form of alpha-adducin is predicted to result in an altered carboxyl terminus that would eliminate a protein kinase and calmodulin binding site. Seven nucleotide substitutions and 4 insertion/deletions were also identified. The 5' region of the human alpha-adducin gene contains one Sp1 site, two AP2 sites, and two CAAT boxes. No TATA box was apparent, consistent with features of a housekeeping gene. We have mapped another cDNA within the first intron of the human alpha-adducin gene, suggesting overlapping genes in this 4p16.3 genomic region. PMID- 7774964 TI - Allergic bronchopulmonary aspergillosis: review of 20 cases. AB - An account of clinical, radiological and laboratory findings in 20 cases of allergic bronchopulmonary aspergillosis, seen over a period of 6 years is presented. All patients showed blood eosinophilia (with 30% having an absolute eosinophil count (AEC) of over 2000 mm3) and a positive immediate skin reaction. However, dual skin reaction with Aspergillus fumigatus antigen was observed in 7 (35%) cases. Serum precipitins against A. fumigatus antigen was detected in all cases while culture of sputum yielded A. fumigatus in 15 (75%) cases. Areas of consolidations of various sizes, shapes and number (80%) and irregular infiltrations (60%), either shifting in nature (85%) or recurrent at same site (35%), were the main radiological findings. PMID- 7774963 TI - Allergic bronchopulmonary aspergillosis: a retrospective study of 35 cases. AB - Clinical profile of 35 patients with allergic bronchopulmonary aspergillosis (ABPA) was analysed. The disease was found to be more frequent among females. Constitutional symptoms, expectoration, increased breathless and poor control of asthma were the main presenting features. Skin reactivity against aspergillin and Candida was positive in 30 and 2 cases, respectively. Precipitating antibodies against Aspergillus species was positive in 28 cases, and against Candida albicans in 2 cases. Sputum grew either Aspergillus or C. albicans or both in 19 patients. Absolute eosinophilia was observed only in one third of cases. Chest skiagram revealed characteristic central/proximal bronchiectasis and/or fleeting shadows in all cases. No specific pattern was observed on spirometry. There was no correlation between the duration of bronchial asthma, sputum culture and serology results. Most patients responded well to steroids. One striking feature of the study was that one third of the cases were misdiagnosed as pulmonary tuberculosis and were treated with antitubercular drugs for varying periods of time. A high index of clinical suspicion with appropriate laboratory tests are required to identify these cases. PMID- 7774965 TI - Correlative study of histopathology and bacteriology in patients of tubercular lymphadenitis. AB - Histopathology as well as bacteriology of lymph node specimen are useful diagnostic tools for tuberculous lymphadenitis. In the present study, a total of 71 cases of lymphadenitis were selected for histopathological and bacteriological studies. Only 46 patients had caseating type and 4 had non-caseating type of tuberculous lymphadenitis while 21 patients revealed non-specific chronic lymphadenitis on histopathological examination. Only 6 lymph node smears were positive for acid fast bacilli (AFB), 19 cases were positive for mycobacterial culture growth. Thus, it is not necessary that the cases which are histopathologically positive will be positive for culture as well. Therefore, both bacteriology and histopathology are complimentary diagnostic tools for tuberculous lymphadenitis. PMID- 7774966 TI - Histoplasmosis in India: current status. PMID- 7774967 TI - Upper zone opacity mimicking lung cancer. PMID- 7774968 TI - Right axis deviation and right ventricular hypertrophy in constrictive pericarditis. PMID- 7774969 TI - Microfilaria in bronchial aspirate. AB - A 65-year-old female was evaluated for suspected bronchogenic carcinoma. The chest x-ray revealed a left parahilar opacity with a raised left dome of diaphragm. Fiberbronchoscopy showed an oedematous and hyperemic left main bronchus but no growth was visualised. Bronchial biopsy did not show any evidence of neoplasm. However, the bronchial aspirate smear examination showed one microfilaria. Post bronchoscopic roentgenogram done on the next day revealed clearing of left parahilar shadow and a normal diaphragm. The patient responded well to 300 mg of diethylcarbamazine given in divided doses for 3 weeks. PMID- 7774970 TI - Immunization coverage and the knowledge and practice of mothers regarding immunization in rural area. AB - One hundred and thirty mothers in the age group (15-44) years and 142 children aged (12-59) months were selected by cluster sampling method from nine villages in Wardha district. Out of this 100 mothers and 122 children could be contacted for evaluation of immunization coverage and assessing maternal knowledge and practice regarding immunization. 52.5% children were fully immunized and 45.1% were partially immunized. Vaccine coverage for B.C.G. and primary doses of DPT/OPV was 95.9% and above 85% respectively. It was 57.4% for measles and 63.04% for booster dose of DPT/OPV. Drop-out rate from second to third dose of DPT/OPV was 5.3% and from third to booster dose was 36.96%. Mothers had a fair knowledge regarding need for immunization but a poor knowledge regarding the diseases prevented and doses of the vaccines. Commonest side reactions reported were fever (36%) and pain at injection site (33%). Contraindications listed by mothers were mild cold (41%), mild fever (24%) or loose stools (14%). Health workers were the major source of information and 76% knew the use and maintenance of immunization cards. PMID- 7774971 TI - Prevalence of hepatitis B surface antigen and antibody among hospital admitted patients in Manipal. AB - 184 indoor patients suffering from various hepatic as well as non-hepatic disorders admitted in Kasturba Medical College & Hospital, Manipal during the year 1989 were studied for the presence of HBs Ag and anti HBs by ELISA. As viral hepatitis specially hepatitis B is a major public health problem in all parts of the world, this type of study will give an idea about the preponderance of hepatitis infection among hospital admitted patients. PMID- 7774972 TI - Nutritional status of under five children in an urban slum community of Calcutta. AB - Nutritional status particularly in relation to the possible risk of morbidity and mortality in children has long been recognised as a field of major concern. A cross-sectional study was undertaken with 1280 under five children in the urban slum community of Chetla, the field practice area of All India Institute of Hygiene & Public Health, Calcutta, during 1991 to identify their nutritional status. Wt/age being the most sensitive indicator was considered; and the children were graded using the Indian Academy of Pediatrics classification. It is evident from table 1, that more than half of the under five children were undernourished in the series, 27.7%, 16.8%, 5.3% and 1.8% being suffering from grade I, II, III and IV undernutrition respectively. PMID- 7774973 TI - A short communication on occurrence of rheumatic diseases attending hospital. AB - A total of 4800 patients suffering from rheumatic diseases, attending Department of Physical Medicine, Burdwan Medical College Hospital, West Bengal, during the period from January 1991 to June 1991, were studied. Out of these 4800 cases, soft tissue rheumatism cases were maximum (57%), followed by osteo-arthrosis cases (36%), rheumatoid arthritis (5.2%), rheumatic arthritis (0.4%), ankylosing spondylitis (0.6%), osteo-chondrosis (0.7%) and gouty arthritis (0.1). Soft tissue rheumatism cases were common (62.8) in age group 20-40 years, mainly (58.4%) in female and maximum (37%) of lumbosacral strain. Osteo-arthrosis cases were highest (53.9%) in 40-60 years of age with female preponderance (57.2%) and mainly (49%) of cervical spondylosis. PMID- 7774974 TI - Health financing in India. PMID- 7774975 TI - Evaluation of anthropometric indices of malnutrition in under five children. AB - Anthropometric indices in the assessment of malnutrition in under five children are being indiscriminately used especially when a community based survey is conducted and so the estimated prevalence of malnutrition varies in different methods. In this study a comparison of these common anthropometric measurements is done in order to find out the best method suitable for individual assessment of malnutrition. The evaluation technique discussed in this paper consists of comparison of the efficiency of various anthropometric measurements in detecting malnutrition and was judged in terms of specificity, sensitivity and predictive value. The test is most efficient when the sensitivity and specificity attain unity. In this study it is shown that weight for age and Body Mass Index (BMI) attain higher value of delta [delta = 1-(alpha + beta)], where - alpha is false positive value and beta is false negative value) and low value of delta standard error of which proves that the best method of assessing malnutrition using various anthropometric measurements is weight for age as against body mass index. PMID- 7774976 TI - Dietary cravings and aversions during pregnancy. AB - Although nausea and vomiting in early pregnancy has been studied in detail, there is little information available regarding dietary aversions and some cravings during pregnancy. To study the prevalence and factors associated with dietary aversions and cravings during pregnancy, a survey was carried out on 1000 randomly selected pregnant women attending antenatal clinics in a district in southern Sri Lanka. In this group 473 (47.3%) had pregnancy cravings for wide variety of foods: sour food 65%, unripe fruits 40%, meat and fish 47%, ripe fruits 30%, food from alms giving 26% and jam and bread fruit 22%. Ninety nine per cent of those who had pregnancy cravings had made special attempt to obtain the food of their choice and all of them had their cravings satisfied by eating the food of their choice. Pregnancy cravings was significantly higher in women who married after a love affair's than in those who had on 'arranged' marriage (p < 0.05), in women who were superstitious (believed in devil dancing and gods) than in those who were not (p < 0.05), and in women with a family income of less than Rs. 2,500 than in those with an income of more than Rs. 2,500 (p < 0.05). PMID- 7774977 TI - Dietary patterns and selected anthropometric indices in reproductive age women of a slum in urban: Kurnool. AB - Dietary intake in pregnant, lactating and non-pregnant nonlactating women of an urban slum in Kurnool, A.P. are about 30% less than the ICMR recommended daily allowances. Heights and weights of the subjects are similar to the National Nutrition Monitoring Bureau's values for slum women and some inter-religious difference is observed in the anthropometry of the subjects. PMID- 7774978 TI - EEG predictability: adequacy of non-linear forecasting methods. AB - The predictive properties of EEG segments were analyzed. The sample included alpha, delta as well as spike and wave EEG activity recordings. Most of these segments are better described with non-linear autoregressive models, and a non linear forecasting algorithm is routinely required. In terms of their predictive properties, segments can be divided into unpredictable, predictable and very predictable, these three groups being similarly represented among the alpha activity EEG segments. In EEG segments with alpha activity, poor predictability is associated with poor organization of the rhythmic pattern. Concerning dynamic properties, it was found that cyclic skeletons were highly represented among the very predictable segments, which reflect a contribution of the deterministic component of the autoregressive model to the predictability of the segments. Notable contributions of the noise component may explain the properties of unpredictable segments. These results point to a great diversity of predictive patterns among EEG recordings. Other factors besides the existence of chaotic dynamics must be regarded. PMID- 7774979 TI - A fuzzy logic diagnosis system for classification of pharyngeal dysphagia. AB - Identification and classification of the dysphagic patient at risk of aspiration is important from a clinical point of view. Recently, we have developed techniques to quantify various biomechanical parameters that characterize the dysphagic patient, and have developed an expert system to classify patients based on these measurements. The purpose of the present investigation was to develop a fuzzy logic diagnosis system for classification of the patient with pharyngeal dysphagia into four categories of risk for aspiration. Non-invasive acceleration and swallow pressure measurements were obtained and five parameters were extracted from these measurements. A set of membership functions were defined for each parameter. The measured parameter values were fuzzified and fed to a rule base which provided a set of output membership values corresponding to each of the categories. The set of output values were defuzzified to obtain a continuous measure of classification. The fuzzy system was evaluated using the data obtained from 22 subjects. There was a complete agreement between the fuzzy system classification and the clinician's classification in 18 of the 22 patients. The fuzzy system overestimated the risk by half a category in two patients and underestimated by half a category in two patients. The fuzzy logic diagnosis system, together with the biomechanical measures, provides a tool for continued patient assessment on a daily basis to identify the patient who needs further videofluorography examination. PMID- 7774980 TI - PC program for assessing the effect of a treatment when subjects are growing: comparative studies. AB - We describe, illustrate, and make available a menu-driven PC program which can be used to assess the effect of a treatment on growth when random allocation of subjects to the treatment and control groups is not feasible. Three different estimators of, and confidence intervals for, this effect are computed, namely, the simple gains, standardized gains, and covariance adjusted estimators. It is shown by means of several examples that these estimators can differ substantially, and some guidelines for choosing between them in specific circumstances are provided. PMID- 7774981 TI - PC program for comparing two regression lines over a specified finite interval. AB - A method due to Tsutakawa and Hewett (Biometrics 34 (1978) 391-398) for comparing two regression lines over a specified, finite interval has been implemented. We describe and illustrate the procedure and program, and make the latter available to interested readers. PMID- 7774982 TI - PC program for determining the dose necessary to produce a given amount of change. AB - Given a simple linear regression equation of the form D = alpha + beta Z, it is well-known how to predict, and construct confidence intervals for, the value of D corresponding to a given Z. In this paper we describe, illustrate and make available a menu-driven PC program which can be used to solve the inverse problem, namely, to estimate and construct confidence intervals for the value of Z corresponding to a given value of D. We describe the procedure in the context of a dose-response relationship, where it is desired to estimate the dose (Z) to effect a given amount of change (D), but the method is more general than this. In particular, it may be usefully applied in calibration problems where one may wish to estimate the true value of a measurement given the value as read from a measuring device. PMID- 7774983 TI - PC program for simultaneously testing equality of means and variances for paired bivariate normal data. AB - A menu-driven PC program for simultaneously testing the equality of means and variances for paired bivariate normal data is described, illustrated and made available. While the corresponding tests for independent samples are well-known and widely implemented, in the paired situation only the test for no change in mean values (the paired t-test) has been similarly covered. Tests for no change in variability, while important, are less well-known and not implemented in most commercial statistical computing programs. PMID- 7774984 TI - PC program extending the Potthoff-Roy longitudinal data analysis model to allow missing data: Kleinbaum's method. AB - Potthoff and Roy (Biometrika, 51 (1964) 313-326) generalized the multivariate analysis of variance model into a form that is especially useful for the study of longitudinal growth curve data. Applications of this method have, however, been limited by the requirement that each case in the sample be measured at the same set of time points, i.e. there can be no missing data. In this paper we describe, illustrate, and make available a user-friendly, interactive PC program implementing Kleinbaum's (J Mult Anal, 3 (1973) 117-124) extension of the Potthoff-Roy model to allow incomplete measurement sequences. These missing data are permitted to arise either randomly or by design as in mixed longitudinal studies. PMID- 7774985 TI - A new model for blood flow through an artery with axisymmetric stenosis. AB - Presented herein are the studies on the flow behavior of a blood type suspension through a circular tube with an axisymmetric stenosis. The suspension of the cells in plasma is represented by a layered fluid model, with a marginal cell free layer of the suspending medium near the wall, a central core region and an annular layer of a biviscous fluid layer. It is understood that the proposed model may contribute to the inbuilt mechanism for drag reduction and prevention of the further development of the stenosis. The concept of lubricating pipe lining for transporting various industrial fluids is well represented through three-layered core-annular flows. The governing equations are solved numerically by using finite element method. The velocity fields, including separation and reattachment points, and the distribution of pressure and wall shear stresses have been brought out and discussed. The results of the analysis show that the presence of the marginal cell-free layer reduces the wall shear stresses and the length of the flow reversal zone. The non-Newtonian character of the suspension is helpful in reducing the abnormal effects of the stenosis. The model thus establishes the inbuilt character of blood for decreasing the stresses and this, in turn, reduces the load on the heart in propelling the blood. PMID- 7774986 TI - A computer program for the analysis of chromatograms used in pharmacokinetic studies. AB - An analog/digital (A/D) converter and software written in BASIC language have been developed for the analysis of chromatographic data which are needed for pharmacokinetic (PK) studies in humans and in experimental animals such as dogs and rats. Using an A/D converter, widely sold personal computers produced by NEC or EPSON are applicable to both high-performance liquid-chromatography (HPLC) data analysis and PK analysis. When chromatographic data is taken up by the computer and treated as a variable, a maximum of 12,000 data points are saved by the computer. As 10 digital data points are taken up by the computer per second through the A/D converter, the maximum run time of a chromatogram is 20 min. For the purpose of HPLC analysis, however, five digital data points per second are usually enough for routine analysis. In this software, the program is written to take and save five digital data points/s. Therefore, the maximum run time of this software increased to 40 min per chromatogram. All the digital data through the A/D converter are saved into the data file on a floppy disk or hard disk. For the chromatogram analysis, both automatic peak identification and manual peak identification, which must be selected with the use of the mouse driver, are available. All the data, peak area, peak height, etc. are also saved into the data file. After a calibration curve is produced, following the input of peak analysis data of known spiked samples, the drug concentration for each sample is estimated. These concentration-time data are also saved into the data file.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7774987 TI - Automating the sleep laboratory: implementation and validation of digital recording and analysis. AB - OBJECTIVES: We report on the implementation of digital processing in a large clinical and research sleep laboratory. The system includes the digital collection, display, analysis, and repository of physiological signals collected during sleep. METHODS: After describing the original analog system, the computer equipment and software necessary for the digital implementation are presented and we explain our algorithms for rapid eye movement (REM) and delta-wave detection. Finally, we describe an experiment validating the digital system of display and analyses. CONCLUSIONS: The digital processing of sleep signals saves computer operator, polysomnographic technologist, and computer time. It also saves resources such as polysomnographic paper and FM tape. The digital signals lend themselves to a large array of analysis techniques and result in improved signal quality. Automated REM and delta-wave detection via digital processing correlate highly with visual counts of rapid eye movements and delta waves. PMID- 7774988 TI - Intracoronary stenting after unsuccessful PTCA. Early restenosis and explanation of stents during bypass surgery. AB - The case of a 63-year-old man is described, who received two intracoronary Palmaz Schatz-Stents after dissection and occlusion following PTCA of two segments of the left anterior descending branch of the left coronary artery. Because of recurrent angina caused by early restenosis in the 'unprotected' segment between the stents, surgical revascularisation was performed and the stents were removed. PMID- 7774989 TI - Effect of gemfibrozil versus lovastatin on increased serum lipoprotein(a) levels of patients with hypercholesterolemia. AB - The aim of this study was to determine the effect of gemfibrozil, compared with lovastatin, in patients with high levels of lipoprotein(a) and on plasma lipid profile. Twenty-seven nondiabetic patients with high levels of plasma lipids and lipoprotein(a), 19 male and eight female, aged 37-68 (mean +/- S.D. 54.2 +/- 7.5) years, were randomly assigned to 2 weeks of treatment with gemfibrozil 600 mg twice daily (14 pts.) or lovastatin 40-80 mg once daily (13 pts.). Patients had fasting plasma total cholesterol levels > or = 6.2 mmol/l, low-density lipoprotein > 4.14 mmol/l and lipoprotein(a) > 0.62 mmol/l. All patients but one had triglycerides > 2.82 mmol/l. There were no statistical differences between both groups in terms of age, sex, clinical diagnosis and previous medication. After 3 months of treatment, gemfibrozil reduced triglycerides (47.9% vs. 24.5%; P < 0.001), very low density lipoprotein (43.9% vs. 24.6%; P < 0.05), lipoprotein(a) (25.3% vs. 4.9%; P < 0.05) and increased high-density lipoprotein (34.4% vs. 11%; P < 0.01) more than lovastatin. Gemfibrozil and lovastatin reduced comparably total cholesterol (21.4% vs. 29.0%; P = NS) and low-density lipoprotein (26.5% vs. 37.3%; P = NS). The plasma levels of high-density lipoprotein and lipoprotein(a) were unchanged significantly by lovastatin. In conclusion, besides well-known efficacy in hyperlipidemia treatment, gemfibrozil also increased high-density lipoprotein and reduced lipoprotein(a), which may have important epidemiologic implications. PMID- 7774990 TI - Effect of aging on left ventricular filling in untreated hypertensive patients. AB - The aim of this study was to evaluate the influence of age and other clinical and echocardiographic parameters on left ventricular filling in a group of 174 untreated patients with mild to moderate hypertension (aged 20-82 years; mean 51.2 years) and in 189 age-matched normotensive subjects. All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. Left ventricular dimensions and indexes of systolic function were similar and within normal limits in both groups. Left ventricular filling was altered in hypertensive subjects < 65 years with a decrease of peak early velocity (peak E), an increase of peak atrial velocity (peak A) and a reduced E/A ratio. However in subjects > or = 65 years, we did not observe any differences in transmitral flow velocity pattern between hypertensive and normotensive subjects. The stepwise regression analysis showed that age alone explains up to 8% of peak E variance, 14% of peak A and 26% of E/A ratio in hypertensives, while in normotensives it explains up to 18% of peak E variance, 50% of peak A and 61% of E/A ratio. The other variables entered into the regression slightly improved the predictive power. In conclusion, age is the major independent factor affecting left ventricular filling in both groups, even if its predictive power was smaller in the hypertensive group. The similarity of diastolic filling pattern in elderly hypertensive and normotensive subjects suggests that the 'aging factor' plays an important role in influencing left ventricular filling pattern so as to mask the effect of hypertension in the elderly patients. PMID- 7774991 TI - Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo controlled study. AB - We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina. PMID- 7774992 TI - Impaired cholinergic peripheral vasodilation and its relationship to hyperemic calf blood flow response and exercise intolerance in patients with chronic heart failure. AB - This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P < 0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P < 0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P < 0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure. PMID- 7774993 TI - Silent myocardial ischemia in diabetics with normal autonomic function. AB - Twenty male diabetic patients (age range, 40-60 years) with normal autonomic function were studied to determine the prevalence of silent myocardial ischemia on exercise as well as ambulatory electrocardiography. The presence and extent of silent myocardial ischemia was also correlated with the severity of atherosclerotic coronary artery disease as determined by coronary angiography. A cohort of 20 matched non-diabetic patients were also included in the study. Silent myocardial ischemia was detected in 50% of the diabetic patients on exercise electrocardiography and in 35% on ambulatory electrocardiography compared with 10% and 5% in non-diabetics by the two methods, respectively (P < 0.01 and P < 0.05, respectively). On exercise testing in diabetic patients, silent myocardial ischemia was detected in 64% of the patients with three-vessel disease, 50% of the patients with two-vessel disease and 20% of the patients with one-vessel disease whereas in non-diabetic patients silent myocardial ischemia was detected in only 18% of the patients with three-vessel disease (P < 0.05) and in none of the patients with two- or one-vessel disease. On ambulatory electrocardiography, only patients (both diabetic and non-diabetic) with three vessel disease manifested silent myocardial ischemia. Total ischemic burden was similar in both the diabetic and non-diabetic patients. We conclude that silent myocardial ischemia occurs in diabetic patients with coronary artery disease more frequently even in the absence of autonomic dysfunction and the prevalence of silent myocardial ischemia is higher in patients with severe degree of coronary artery disease. PMID- 7774994 TI - Use of electrophysiological studies in the diagnosis and treatment of cardiac patients with left ventricular dysfunction and high grade ventricular ectopy. AB - We studied the sudden death occurrence in 28 patients (23 males, age 59.2 +/- 15.6 years) who had a documented cardiac disease with left ventricular dysfunction (ejection fraction < or = 0.4) and high grade ventricular ectopy. None had suffered from spontaneous sustained ventricular arrhythmia and/or syncope. Their diagnosis and treatment were guided by electrophysiological studies. Electrophysiological studies were performed in the antiarrhythmic drug free state. In cases when sustained ventricular arrhythmias could be induced, antiarrhythmic treatment was prescribed according to the results of the electrophysiological studies. In cases of non-inducibility, no antiarrhythmic treatment was prescribed. The patients were followed up for a period of 20.6 +/- 11.2 months. The end points were occurrence of documented spontaneous sustained ventricular arrhythmia and sudden death. None of the 19 non-inducible patients experienced sudden death or spontaneous sustained ventricular arrhythmia. Two of the nine inducible patients died suddenly (P = 0.1). The 3-year sudden death mortality rate of the whole group was 7.5%. We conclude that when cardiac patients with high grade ventricular ectopy and left ventricular systolic dysfunction are treated according to the results of electrophysiological studies, it can be expected that their 3-year mortality rate will be low and significantly inferior to that reported for conventionally treated patients. PMID- 7774996 TI - Significance of ST segment depression during adenosine-induced coronary hyperemia in angina pectoris and correlation with angiographic, scintigraphic, hemodynamic, and echocardiographic variables. AB - Factors determining myocardial ischemia during adenosine-induced coronary vasodilation in patients with angina pectoris are not well defined. To evaluate the angiographic, scintigraphic, hemodynamic, and echocardiographic determinants of ST segment depression during adenosine infusion, 40 patients with angina pectoris underwent technetium-99m sestamibi single photon emission computed tomography and simultaneous two-dimensional echocardiography. Ischemic ST depression occurred in 18 patients (45%). Coronary angiography was performed in all patients and a coronary artery jeopardy score was determined. The sensitivity, specificity, and the predictive accuracy of adenosine-induced ST segment depression in detecting significant coronary artery disease were 53%, 100%, and 60%, respectively, while the corresponding results for detecting reversible perfusion defects were 61%, 92%, and 70%, respectively. Univariate predictors of ST segment depression included the coronary artery jeopardy score, the presence and the extent of reversible perfusion defects, the presence of three-vessel and/or left main coronary artery disease, and diastolic blood pressure at peak adenosine infusion. There was a trend (P = 0.06) to a higher incidence of collateral vessels in patients developing ST segment depression. The coronary artery jeopardy score was found to be the only significant independent predictor of ST segment depression by stepwise multivariate logistic regression analysis. Thus, in patients with angina pectoris, the coronary artery jeopardy score, representing the extent of significant coronary artery disease, is the most important independent predictor of adenosine-induced ST segment depression. ST depression is unusual in the absence of reversible perfusion defects and is also associated with more extensive reversible defects. PMID- 7774995 TI - Plasma lipid profile and coronary artery disease in Brazilian hemodialysis patients. AB - We studied the prevalence of lipid disorders and of coronary artery disease and the main factors affecting plasma lipids in a cohort of Brazilian hemodialysis patients. The investigation comprised 75 adult hemodialysis patients and 200 normal controls matched for age, sex, race and body mass index. Mean values for plasma lipids were within normal limits in the dialysis group. Total cholesterol (184 +/- 44 vs. 201 +/- 46 mg/dl), LDL (110 +/- 36 vs. 131 +/- 44 mg/dl) and HDL (40 +/- 13 vs. 47 +/- 12 mg/dl) were significantly lower in the dialysis patients (P < 0.01), whereas VLDL (32 +/- 14 vs. 21 +/- 12 mg/dl) and triglyceride (161 +/ 71 vs. 111 +/- 70 mg/dl) were increased (P < 0.01). Increased triglyceride was observed in 24% of the dialysis patients, a prevalence two to three times lower than that reported in the literature. In the dialysis group, the variables positively related to total cholesterol were hypertension (P < 0.05) and gender (female) (P < 0.05); to LDL and HDL, hypertension (P < 0.05 and P < 0.01, respectively); and to triglyceride, use of propranolol (P < 0.01). Age, race, duration of hemodialysis, body mass index and plasma creatinine did not affect plasma lipids. The prevalence of coronary artery disease, established by invasive and noninvasive methods, was 10.7% while in the literature 20-35% of the unselected hemodialysis patients present obstructive coronariopathy. We conclude that the plasma lipid profile of Brazilian hemodialysis patients is similar to those reported in American and European literature, whereas the prevalence of hypertriglyceridemia and of coronary artery disease appears to be reduced. PMID- 7774997 TI - Intracardiac varices of the right atrium: a case report and review of the literature. AB - Two broad-based masses arising along the right atrial septum in a 31-year-old man were detected by transesophageal echocardiography and were thought to represent partially calcified myxomas. However, at operation they were cystic structures filled with blood and calcific nodules. Microscopically, they represented varices with phleboliths. Angiography and ultrafast computed tomography may help distinguish this entity from myxomas and other right atrial intracavitary masses. PMID- 7774998 TI - Evaluation of left ventricular filling by echocardiographic atrioventricular plane displacement in patients with coronary artery disease. AB - Mean atrioventricular (AV) plane displacement which resulted from left atrial systole and its ratio to the total diastolic displacement, were determined by echocardiography in 101 patients with coronary artery disease. Ratio of motion of the AV plane caused by left atrial systole to the total diastolic displacement was correlated with late-to-early mitral flow peak velocity index (r = 0.7). Selecting a value of this ratio of the AV plane displacement > or = 44% to define Doppler characteristics indicating impaired left ventricular relaxation, resulted in a high sensitivity, specificity and predictive value. Its value was also validated in another prospectively examined group of coronary artery disease patients. In conclusion echocardiographic assessment of AV plane displacement can be used for the estimation of left ventricular filling in patients with coronary artery disease and particularly in detecting impaired left ventricular relaxation. PMID- 7774999 TI - Anomalous left circumflex in tetralogy of Fallot--a case report. AB - A case of anomalous left circumflex coronary artery coursing the right atrioventricular groove in a patient with the Tetralogy of Fallot is described, a pattern which, to the best of our knowledge, has not been reported earlier. PMID- 7775000 TI - Reversal of dilated cardiomyopathy after chronic tricyclic antidepressant drug withdrawal. AB - Two patients referred for heart transplantation for dilated cardiomyopathy on chronic tricyclic antidepressant treatment are described. Echocardiographic normalization of left ventricular diameters and function were evidenced after drug withdrawal, suggesting drug-induced toxic myocardial disease. The possibility of functional improvement after tricyclic antidepressant drug withdrawal should be kept in mind before including patients with dilated cardiomyopathy in a heart transplantation program. PMID- 7775001 TI - Spontaneous coronary artery dissection associated with oral contraceptive use. AB - A 39-year-old woman presented with acute myocardial infarction due to spontaneous dissection of the left anterior descending artery. This was treated conservatively. She had been on combined oral contraceptive pills from the age of 22. Repeat coronary angiography 7 months later revealed spontaneous complete healing. PMID- 7775002 TI - The connection between lactose and coronary artery disease. PMID- 7775004 TI - Chemical shift differences between free and Fab-bound peptide correlate with a two-stage selection of peptide sequences from a random phage display library to delineate critical and non-critical residues for antibody recognition. AB - Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag octapeptide epitope system. We have analyzed two peptides: Ac-Asp Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH2 (peptide 1), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH2 (peptide 2), which closely corresponds to the original Flag sequence. Enrichment of the peptides with 15N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. PMID- 7775003 TI - Stereoselective synthesis of Xaa psi[CH2CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV-1 protease inhibitors. AB - Two stereoselective syntheses of a new pseudodipeptide isostere, the right-hand hydroxyethylene dipeptidomimetic (Xaa psi[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti-aldol product for the hydroxyethylene isostere via an E-selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc-Phe psi[CH2CH(OH)]Phe. Two diastereomers, (S,S,R) and (S,R,R), are incorporated into an HIV-1 protease inhibitor template which yields potent inhibitors of HIV-1 protease when the pseudodipeptide isostere is Phe psi[CH(OH)CH2]Phe or Phe psi[CH(OH)CH(OH)]Phe. The resulting Phe psi[CH2CH(OH)]Phe-containing inhibitors possess modest potency. PMID- 7775005 TI - Synthesis of a selenomethionine peptide and a preliminary study of transport into Escherichia coli monitored by high-performance liquid chromatography. AB - The tripeptide Gly-SeMet-Gly has been synthesized by a combination of solution and solid-phase methods. Increase in weight of the resin was very nearly theoretical, and purification was straightforward. Its absorption was compared to that of the corresponding peptide, Gly-Met-Gly, in E. coli using HPLC ion exchange separation and fluorometric determination of the disappearance of peptides in the culture medium and the appearance of methionine and selenomethionine in the same culture medium. As E. coli are not known to possess extracellular peptidases, and in fact have been shown to possess transport systems for peptides, this absorption is interpreted as transport of the peptide through the cell wall and membrane into the cytoplasm, endohydrolysis of the peptide, and efflux of the peptides' amino acids. Uptake of both peptides was approximately equal, but was slowed when both peptides were present simultaneously. PMID- 7775006 TI - Chemical phosphorylation of the peptides GGXA (X = S, T, Y): an evaluation of different chemical approaches. AB - An evaluation was made of the two methods most commonly used for phosphorylation of hydroxyamino acids in peptides, i.e. the tetrazole-catalysed phosphitylation by di-tert-butyl-N,N-diethylphosphoramidite followed by oxidation and the phosphorylation by dibenzylphosphochloridate. As model system the sequence GGXA (X = S, T, Y) was used which represents a random-coil sequence avoiding the influence on the reaction kinetics of secondary structure formation. In the case of serine- and threonine-containing peptides, both synthetic methods gave comparable yields of the desired phosphopeptides. The phosphorylation of tyrosine was achieved more favorably via the phosphoramidite method. However, phosphotyrosine peptides are most easily obtained by peptide synthesis using Fmoc Tyr(PO3Me2)OH as building block. The dibenzylphosphochloridate method yields the expected phosphopeptides as the only peptide derivative and in addition, a great number of unidentified by-products which can be removed by ion-exchange chromatography. The phosphoramidite method consistently resulted in three peptide derivatives, i.e. the desired phosphopeptide, the phosphitylated peptide and a bridged derivative with two GGXA fragments linked through a phosphodiester bridge. The derivatives were characterised by RP and ion-exchange chromatography, 31P- and 1H-NMR spectroscopy, and ion-spray and electrospray mass spectrometry. Interestingly, even these mild ionisation techniques resulted in partial fragmentation. The observed fragmentation pathways seem to be a diagnostic tool for the identification of phosphorylation sites in peptides. Both the phosphorylated serine and threonine peptide lost phosphoric acid (98 mass units), the tyrosine peptide lost phenyl phosphate (174 mass units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775008 TI - Designed polyanionic coiled-coil proteins: acceleration of heparin cofactor II inhibition of thrombin. AB - Novel polyanionic proteins were designed to increase the rate of heparin cofactor II (HC) inhibition of alpha-thrombin, an essential protease in the coagulation cascade. Two alpha-helical coiled-coil proteins, a 62-residue dimer containing 8 Glu residues (E8C) and a 104-residue dimer containing 14 Glu residues (E14C), plus two 31-residue control peptides containing 8 Glu residues each (E8A and E8B), were chemically synthesized, structurally characterized and enzymatically assayed. Circular dichroic spectrophotometry indicated that both E8C and E14C formed stable two-chain alpha-helical coiled coils at pH 7 and 25 degrees C. The control peptides were only partially alpha-helical. E14C remained folded at 90 degrees C but E8C was half unfolded at 49 degrees C. Coiled-coil proteins E8C and E14C maximally accelerated by 35- and 33-fold, respectively, the rate of HC inhibition of alpha-thrombin. None of these compounds accelerated antithrombin inhibition of alpha-thrombin, and neither control peptide accelerated HC inhibition of alpha-thrombin. Acceleration of the HC inhibition of alpha-thrombin showed bimodal dependence on the concentration of the polyanionic protein, which is consistent with formation of a HC-coiled-coil-thrombin ternary complex. The results suggest that antithrombotic polyanionic alpha-helical coiled-coil proteins can be designed and synthesized and that the occurrence of secondary structure can be correlated with biological activity. PMID- 7775007 TI - Solution structure of the hydrophilic region of HIV-1 encoded virus protein U (Vpu) by CD and 1H NMR spectroscopy. AB - The HIV-1 specific Vpu is a class I oligomeric membrane phosphoprotein of unknown structure and mechanism. The first experimental evidence for the position of secondary structural elements present in the hydrophilic C-terminal region of Vpu under various solution regimes is reported. CD data for nine overlapping 15 amino acid fragments and 3 longer fragments indicate the presence of only transitory amounts of stable structure in aqueous solution alone, while with increasing trifluoroethanol content limiting structures were found indicating two helical segments in the hydrophilic region of Vpu. These limiting structures were more precisely defined from a detailed study of Vpu41-58, Vpu52-74 and Vpu63-81, by a combination of 2D 1H NMR spectroscopy, distance geometry, and restrained molecular dynamics and energy minimization calculations. Sets of low-energy conformations compatible with the quantitative NOE data indicate that Vpu41-58 has an alpha-helix from residues 42 to 50 while a second helix is found for Vpu52 74 from residues 57 to 69. Vpu63-81 shows only the presence of a single reverse turn at residues 74 to 77, without any evidence of helix, under the same conditions. From CD measurements the first helix extends back to residue 30 and is connected to the N-terminal anchor of Vpu. Thus the hydrophilic region of Vpu consists of two alpha-helices joined by a flexible region of 6 or 7 residues, which contains the phosphoacceptor sites of Vpu at positions 52 and 56. The second helix is followed by a single reverse turn and a flexible C-terminus. PMID- 7775009 TI - Coupling in the absence of tertiary amines. V. Removal of the 2 nitrobenzenesulfenyl (NPS) group with 1-hydroxybenzotriazole in the presence of aniline or N-methylaniline. AB - In a search for conditions of acidolytic removal of amine protecting groups leading to salts of the deblocked amine that can be acylated without addition of a tertiary amine, cleavage of the 2-nitrobenzenesulfenyl (Nps) group with hydroxybenzotriazole (HOBt) in 2,2,2-trifluoroethanol was attempted. The Nps group was smoothly removed, but the resulting salt of the amine component could not be acylated unless deprotonated with a tertiary base. A rationale is now proposed for this unsatisfactory outcome of the cleavage reaction and for the concomitant surprising reduction of HOBt to benzotriazole. Based on the proposed mechanism, a new approach was designed for the removal of the Nps group. It was cleaved with HOBt in the presence of weakly basic nucleophiles such as aniline, N methylaniline or 8-aminoquinoline. The protecting group was transferred smoothly to the amino group of the nucleophilic acceptor leaving the deblocked amine component in the form of its HOBt salt. This was then readily acylated without addition of a tertiary amine. PMID- 7775010 TI - The preferred solid-state conformation of (alpha Me)Trp peptides. AB - The two Z-L-Ala-DL-(alpha Me)Trp-NH2 diastereomeric dipeptides were synthesized from (Z-L-Ala)2(O) and H-DL-(alpha Me)Trp-NH2. The latter racemate, prepared by phase-transfer catalyzed alkylation of the N alpha-benzylidene derivative of alanine amide followed by acidic hydrolysis of the resulting Schiff base, was characterized by X-ray diffraction. The molecular and crystal structure of Z-L Ala-L-(alpha Me)Trp-NH2, separated from its diastereomer by silica-gel column chromatography, was determined by X-ray diffraction analysis. Both independent molecules in the asymmetric unit of the dipeptide adopt a type-II beta-bend conformation. However, only the more regularly folded conformation of molecule B is stabilized by a 1<--4 C = O...H--N intramolecular H bond. The present results indicate that: (i) the C alpha-methylated (alpha Me)Trp residue is a strong beta bend and helix former, and (ii) the relationship between (alpha Me)Trp chirality and helix screw sense tends to be opposite to that of protein amino acids. The implications for the use of the (alpha Me)Trp residue in designing conformationally restricted analogs of bioactive peptides are briefly discussed. PMID- 7775011 TI - Unprotected peptides as building blocks for branched peptides and peptide dendrimers. AB - We describe two new site-specific ligation methods for preparing branched peptide dendrimers such as multiple antigen peptide (MAP). Both methods are based on the general approach of exploiting the specific reaction between a weak base and an aldehyde under acidic conditions so that unprotected peptides can be used as building blocks. A weak base such as benzoyl hydrazine or 1,2-amino thiol of cysteine was attached to the N-terminal of an unprotected peptide as nucleophile to react with the alkyl aldehyde on the core matrix of MAP to form a stable hydrazone linkage or a five-membered thiazolidine ring, respectively. Two synthetic peptides rich in basic amino acids such as lysine and arginine were used as models in the ligation reactions in solution to give peptide dendrimers containing four or eight copies of peptide immunogens. The resulting macromolecules with the MW ranging from 5 to 16 kDa were unambiguously characterized by laser-desorption mass spectrometry. Furthermore, we also optimized the conditions of these ligation reactions using elevated temperature and a water-miscible organic co-solvent to give a combination of rate enhancement about 10 fold. These optimizations allowed the ligation reactions to be completed in < 4 h instead of 2-3 days. Our ligation approach also has the advantages of flexibility so that peptides can be attached through the amino or carboxyl terminus to the core matrix. The phenyl hydrazone linkage and the five-membered ring were found to be stable at physiological pH suitable for immunization. Thus our results provide two practical and useful methods for the synthesis of macromolecular peptide dendrimers for vaccines, artificial proteins, and enzymes. PMID- 7775012 TI - Structural characterizations of neuropeptide tyrosine (NPY) and its agonist analog [Ahx5-17]NPY by NMR and molecular modeling. AB - The structures of human NPY and of its centrally truncated agonist analog [Ahx5 17]NPY have been investigated in DMSO-d6 by two-dimensional NMR and by molecular modeling. For both peptides, a complete resonance assignment was achieved and a large number (more than 200) of inter-residue NOE connectivities were observed, including long-range connectivities between the N- and C-terminal ends of the chain. Molecular models were calculated using NOE constraints by distance geometry, simulated annealing and conjugate gradient energy minimization. The results indicate that both peptides are folded in the center of their chain, NPY adopting the hairpin shape, whereas the central portion of [Ahx5-17]NPY is characterized by relatively large loops. In contrast to previous models, practically no alpha-helical structure exists for these peptides under our conditions, but two beta-turns are found in NPY and one in [Ahx5-17]NPY. The proximity of the terminal ends could be the determinant factor for their activity. PMID- 7775014 TI - Synthesis and separation of protected tripeptide epimers by RP-HPLC. AB - Twenty three epimeric pairs of protected tripeptides of the type Z-Ala-Xaa-Val OMe have been synthesized by conventional coupling procedures in solution. Optimal conditions for baseline separation of LLL/LDL epimers were found by high performance liquid chromatography on a RP-18 column with aqueous methanol as mobile phase. The hydrophobic parameters (log kw) were determined for all tripeptides. PMID- 7775013 TI - Specificity and formation of unusual amino acids of an amide ligation strategy for unprotected peptides. AB - An important step in the recently developed ligation strategy known as domain ligation strategy to link unprotected peptide segments without activation is the ring formation between the C-terminal ester aldehyde and the N-terminal amino acid bearing a beta-thiol or beta-hydroxide. A new method was developed to define the specificity of this reaction using a dye-labeled alanyl ester aldehyde to react with libraries of 400 dipeptides which contained all dipeptide combinations of the 20 genetically coded amino acids. Three different ester aldehydes of the dye-labeled alanine: alpha-formylmethyl (FM), beta-formylethyl (FE), and beta,beta,beta-dimethyl and formylethyl esters (DFE), were examined. The DFE ester was overly hindered and reacted with N-terminal Cys dipeptides (Cys-X). Interestingly, it also reacted slowly with the sequences of X-Gly where Gly was the second amino acid and the X-Gly amide bond participated in the ring formation. Although the FE ester reacted similarly as the FM ester in the ring formation, the subsequent O,N-acyl transfer was at least 30-fold slower than those of the FM-ester. The FM alpha-formyl methyl ester was the most suitable ester and was reactive with dipeptides of six N-terminal amino acids: Cys, Thr, Trp, Ser, His and Asn. The order and extent of their reactivity were highly dependent on pH, solvent and neighboring participation by the adjacent amino acid. In general, they could be divided into three categories. (1) N-Terminal Cys and Thr were the most reactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775015 TI - Prediction of protein secondary structures from their hydrophobic characteristics. AB - Deciphering the native conformation of proteins from their amino acid sequences is one of the greatest challenges in the field of molecular biology. The successful prediction of structural class may help to improve the accuracy levels of structure (secondary and tertiary) predictive schemes in globular proteins. In our earlier works we developed a new surrounding hydrophobicity scale for the 20 amino acid residues applicable for both globular and membrane proteins and used it successfully to predict the transmembrane helical and strand segments in membrane proteins. In this article we propose (i) rules to predict the structural class of proteins and (ii) a new predictive scheme for forecasting secondary structures of globular proteins, with the use of the new hydrophobicity scale. This scheme predicts the structural class and secondary structures of globular proteins to 92 and 82% levels of accuracy, respectively, far better than the levels from other existing methods. PMID- 7775016 TI - Efficient synthesis of metal binding peptides incorporating aminodiacetic acid based ligands. AB - New N alpha-Fmoc/Bu(t) protected amino acids bearing half-EDTA side chains (CH2)nN(Ada-O-Bu(t))2 n = 1 (5), n = 2 (24), n = 3 (10), n = 4 (15) were prepared in satisfactory yields. These derivatives can be conveniently used in a solid phase peptide synthesis as they are devoid of serious shortcomings of Boc/Bzl based syntheses of metallopeptides, such as preliminary peptide capping as well as undesired lactamization of 5 during the peptide synthesis. Munksgaard 1995. PMID- 7775017 TI - Simultaneous differential scanning calorimetry, X-ray diffraction and FTIR spectrometry in studies of ovalbumin denaturation. AB - The new application of differential scanning calorimetry (DSC) and the susceptibility of ovalbumin to alpha-chymotrypsin gave a quantitative estimation of protein denaturation in solid ovalbumin. Solid ovalbumin in granules with 11% of water was heated at 100 degrees C in closed and nonclosed ampules. In order to compare effects of size and crystal structure, two proteins (bovine albumin and gamma-globulin) were examined at similar conditions for the extent of denaturation. Ovalbumin and bovine albumin showed similar extents of denaturation, but gamma-globulin, with a very different molecular mass, showed the maximal conformational changes. The enthalpy of denaturation was measured to elucidate the conformational changes in solid proteins. Its value was used for calculation of the degree of denaturation. The thermodynamic data associated with transition were calculated and the number of bonds broken during denaturation was determined. Intrinsic fluorescence was utilized in order to compare these two methods. Moreover, X-ray diffraction and FTIR spectrometry were applied to native and denatured proteins. PMID- 7775018 TI - Synthesis of dipeptide 4-nitroanilides containing non-proteinogenic amino acids. AB - A series of tert-butyloxycarbonyl amino acid 4-nitroanilides, including N alkylated amino acids and (R)-thiazolidine-4-carboxylic acid, (S)-oxazolidine-4 carboxylic acid. (4S,5S)-5-methyloxazolidine-4-carboxylic acid, (4S,5R)-5 methyloxazolidine-4-carboxylic acid, (S)-azetidine-2-carboxylic acid, (S) pipecolic acid and (S)-3,4-dehydroproline, were prepared conveniently by the isocyanate method or the mixed anhydride procedure. The resulting amino acid 4 nitroanilides were extended to corresponding dipeptide 4-nitroanilides with tert butyloxycarbonyl-(S)-alanine. In the case of sterically hindered amino acid 4 nitroanilides the mixed anhydride procedure with diphenylphosphinyl chloride was successful. PMID- 7775019 TI - Amino-acid conjugates of the hapten 2-phenyl-4-ethoxymethylene-5(4H)-oxazolone. Synthesis and confirmation of structure. AB - 2-Phenyl-4-ethoxymethylene-5(4H)-oxazolone (PhOx = CHOEt) was reacted with methylamine, and 2-phenyloxazole-4-carboxylic acid was coupled with methylamine. The spectroscopic properties of the two products were compared in order to confirm that aminolysis of PhOx = CHOEt occurs by displacement of the ethoxy group to give 2-phenyl-4-(substituted-methylene)-5(4H)-oxazolones and not by attack at the oxazolone-carbonyl followed by rearrangement to give 2 phenyloxazole-4-carboxamides. Ten crystalline conjugates were prepared and characterized by reacting PhOx = CHOEt with an excess of unprotected di- and trifunctional amino acid anions followed by purification by washing them with hydrochloric acid. PMID- 7775020 TI - The linked phi psi chain plot for visual comparison of the backbone conformation of peptides and proteins. AB - A new graphic method is described for presenting in two dimensions the phi and psi dihedral angles that describe the backbone conformation of a peptide or protein chain. For each residue in sequence, phi and psi are plotted as dots on the y-axis above the next two points on the x-axis representing the residue number. Each dot is linked to the next dot by a slanting line segment (link) and each cis-peptide bond (omega approximately 0 degrees) between residues X and Y is indicated by marking dots psi X and phi Y with a diamond. This linked phi psi chain plot is more useful than an unlinked phi psi chain plot for visually recognizing helices, sheets and turns and for graphically comparing several protein structures. Overlaying the linked phi psi chain plots for 15 beta hairpins classified as type-I' beta-turns revealed that three were significantly different from the rest. The dihedral angles (mean +/- standard deviation) of the loop residues (L1, L2) for a cluster of 12 beta-hairpins with an inverse-common, type-I' beta-turn (phi L1 = 52 +/- 7 degrees, psi L1 = 40 +/- 8 degrees, phi L2 = 80 +/- 9 degrees, psi L2 = -1 +/- 13 degrees) are similar to the standard dihedral angles for the type-1' turn (60, 30, 90 and 0 degrees, respectively). PMID- 7775021 TI - Cyclic analogues of wasp kinins from Vespa analis and Vespa tropica. AB - Syntheses are described of two bradykinin-like kinins isolated from Vespa analis (G-R-P-P-G-F-S-P-F-R-V-I, VSK-A) and Vespa tropica (G-R-P-Hyp-G-F-S-P-F-R-V-V, VSK-T) and of their cyclic analogues. Linear dodecapeptides were prepared by the solid-phase procedure based on Fmoc-chemistry, and cyclization was carried out by the diphenyl-phosphorylazide method. Peptide were characterized by amino acid analysis, optical rotation, analytical HPLC and FAB-MS. The conformational features of the cyclic and linear kinins were determined by circular dichroism measurements in water, 95% trifluoroethanol and 8 M guanidinium chloride. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that cyclic wasp kinins were 50-100 times less potent than their linear analogues. Moreover, cyclo-VSK-A and cyclo-VSK-T behave like kininase inhibitors by preventing the degradation of straight kinins. PMID- 7775022 TI - Engineering of five 88-residue receptor-adhesive modular proteins containing a parallel alpha-helical coiled coil and two RGD ligand sites. AB - Several 88-residue proteins were designed, synthesized and examined as receptor adhesive modular proteins (RAMPs). Three covalent and two noncovalent dimers were made from two 44-residue peptide chains containing three structural modules: RGD A23a (ligand-spacer-coil) and A9a-RGD (coil-spacer-ligand). The ligand module contained the tripeptide Arg-Gly-Asp (RGD). The coil modules A9a and A23a were five-heptad alpha-helices engineered by Hodges and co-workers [Int. J. Peptide Protein Res. (1992) 40, 171-179]. By circular dichroic spectroscopy, each of these five RAMPs contained an alpha-helical coiled coil. The disulfide-bridged dimer RGD-A23a/RGD-A23a and its reduced form (RGD-A23a)2 had two N-terminal RGD sites. The disulfide-bridged dimer A9a-RGD/A9a-RGD and its reduced form (A9a RGD)2 had two C-terminal RGD sites. However, the disulfide-bridged heterodimer RGD-A23a/A9a-RGD had one RGD site at each terminus with a 50 Angstrum coiled coil between them. The temperature at the midpoint of unfolding for each of the covalent homodimers RGD-A23a/RGD-A23a (67 degrees C) and A9a-RGD/A9a-RGD (69 degrees C) was slightly higher than that of the corresponding noncovalent homodimer (RGD-A23a)2 (62 degrees C) or (A9a-RGD)2 (68 degrees C) but much lower than that of the covalent heterodimer RGD-A23a/A9a-RGD (79 degrees C). The enthalpy and entropy of thermal unfolding were also significantly greater for the heterodimer than for the four homodimers, consistent with the heterodimer having the most stable coiled coil. Although the distance between its RGD sites was at least 50 Angstrum greater than that for the homodimers, this heterodimeric RAMP was only as active as the homodimers A9a-RGD/A9a-RGD and (A9a-RGD)2 in inhibiting the adhesion of A2058 melanoma cells to extracellular matrix proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775023 TI - A novel oxidation-labile linker for solid-phase peptide synthesis. PMID- 7775024 TI - Triangular space and the development of a working model in the analysis. AB - Two clinical examples are presented in order to demonstrate how the analyst uses what he perceives to be the patient's impact on his ability to think, in constructing an effective psychoanalytic working model. The two clinical cases, very different in character and in the countertransference difficulties they cause, lead to the construction of quite diverse working models, although an oedipal illusion plays a central role in both. The presentation is based on the premise that psychic space exists and that the shape of the psychic space of one individual affects by way of projection the shape of the psychic space of another. In the discussion the author traces Bion's concept of the working model and the abstractions which can be developed from it, as well as the use of Bion's theory in Britton's discovery of the effect that a patient's personal model of the oedipal situation can have on the mind of the analyst. PMID- 7775025 TI - 'No greater, richer, more mysterious subject [...] than the life of the mind'. An early exchange of letters between Freud and Einstein. AB - The exchange of letters between Freud and Einstein to which we owe 'Why war?' was preceded three years earlier, in 1929, by another, hitherto unknown, brief correspondence. It began with a rather peculiar congratulatory missive sent by Freud to Einstein on the occasion of the latter's fiftieth birthday, against which the recipient defended himself with jovial sarcasm. Freud explained his 'transgression' in a long and illuminating letter, in which he characterised it as an expression of envy. In so doing he assigned an exceedingly benign quality to the affect of envy and suppressed the obvious admixture of aggression. The author shows in her interpretation that Freud's envy was directed chiefly towards the undisputed world renown of the much younger man, whose work had already been distinguished with the Nobel Prize. Freud may possibly have known that, not long before, Einstein had declined to second the nomination of the founder of psychoanalysis for a Nobel Prize; at any rate, his letter describes in telling images the particular difficulties and handicaps associated with the investigation of human mental life. PMID- 7775027 TI - Psychoanalysis in Britain: points of cultural access, 1893-1918. AB - An attempt is made here to organise a body of facts available in the published literature concerning who, when and why Freud and his ideas were first noticed during the early years of psychoanalysis. Specific citations and references mentioning Freud reveal a surprisingly wide range of different kinds of cultural interest. In fact, we can identify seven different cultural locations which adopted some element of the ideas of Freud for specific reasons: (i) the interest in the theory of hysteria, from the Society for Psychical Research, commencing in 1893; (ii) the interest in the psychoanalytic theory of sexuality, from Havelock Ellis, from about 1895, in support of radical attitudes towards sexual freedom; (iii) as part of the reaction against the pessimistic attitude to treatment in British psychiatry, from around 1905 onwards; (iv) the endeavour of W. H. R. Rivers and others to create an empirical science of psychology embracing scientific psychoanalysis, around 1910-15; (v) the application of psychoanalysis to the psychological novel by writers and also to understanding the creative process, using Freud's theory of symbols, around 1913; (vi) the attraction of some progressive educationalists to Freud's outline of child development, from 1913; and (vii) the struggle of philosophers, including Bertrand Russell, to comprehend the implications of the psychoanalytic view of the unconscious. It is claimed that the multivalent quality of Freud's ideas contributed to the success of psychoanalysis over the suggestive therapies, and in the conflicts with dissenters within the psychoanalytic movement. PMID- 7775026 TI - Jones on ice: psychoanalysis and figure skating. AB - This paper rescues Ernest Jones's largely-unknown book, 'The Elements of Figure Skating' (1931/1952), from relative obscurity and argues for its place in the psychoanalytic literature. In the first section, the authors situate Jones's passion for figure skating by turning to various historical and biographical sources, and to personal correspondence with Jones's son, Mervyn Jones. In the second section, they offer the first textual reading of Jones and skating within a psychoanalytic framework. This approach, they argue, is long overdue since Jones explicitly claimed that the 'Elements' was motivated by his interest in the 'psychological' problems of the beginning skater, and with the task of instruction therein. The authors rely heavily on passages from the 'Elements', in part because the book is out-of-print and unavailable to most readers, but also because Jones's own words are an exemplary instance of his intense transference to psychoanalytic theory during his extra-professional time as a skater. They conclude the paper by arguing that Jones ultimately advocates a position beyond psychology when he idealistically embraces 'exact knowledge' as the royal road to masterful skating. PMID- 7775028 TI - Psychoanalytic realities and the analytic goal. PMID- 7775029 TI - Anna Freud's adult psychoanalytic technique: a defence of classical analysis. AB - The four parts of this paper try to give a picture of Anna Freud's views about adult psychoanalytic technique. In the first part, an historical review is given of the main points that Anna Freud made about the development of classical technique. In the second part, a clinical sketch is presented of the author's own personal training analysis with Anna Freud, as an illustration of her actual analytic approach in practice. The third part presents a very brief summary of the historical development of 'modern' psychoanalytic contributions and the controversies that resulted. Finally, the fourth part summarises several major areas of differences that Anna Freud believed had developed in recent decades between classical analysis and the more 'modern' varieties that focus predominantly on the transference and the 'here-and-now' interaction between patient and analyst. By outlining the many differences, the presentation attempts to convince some of the new generation of psychoanalysts in our pluralistic world of the continued value of the underlying principles behind classical technique. PMID- 7775030 TI - Psychic reality and unconscious belief. PMID- 7775031 TI - Psychic reality in psychoanalytic theory. PMID- 7775032 TI - Psychic reality or various realities. PMID- 7775033 TI - Psychic reality and clinical technique. PMID- 7775034 TI - Addressing the psychic reality of the borderline child. PMID- 7775035 TI - Playing with reality: the development of psychic reality and its malfunction in borderline personalities. PMID- 7775036 TI - Analysing children's dreams. PMID- 7775037 TI - Trauma and termination. AB - The author suggests a particular reading of the thesis put forward by Freud in 'Analysis terminable and interminable' that an effective and more definitive conclusion may be expected in analyses of cases with traumatic aetiology. This reading shifts the emphasis from the patient's history to the possibility of its crystallising in focal nuclei emerging within the analytic relationship under the pressure of the termination. The revival of separation anxieties which cannot be worked through, and their crystallisation in precipitating traumatic events, may give rise to decisive psychic work allowing the analysis to be brought to a conclusion. Two case histories are presented to show how the end of the analysis assumes the form of a new trauma, which reactivates in the present, traumatic anxieties from the patient's own infantile history. In the first case a premature birth and in the second a miscarriage, originally experienced as isolated automatic events without time or history, are relived in the terminal phase as vicissitudes of the transference, so that new meaning can be assigned to them and they can be withdrawn from the somatic cycle of repetition. The powerful tendency to act out and the intense countertransference pressure on the analyst are discussed in the light of the specificities of this phase, which is crucial to the success of the analysis. This leads to a re-examination, in the concluding notes, of some theoretical questions inherent in the problem of the termination and, in particular, to a discussion of the ambiguous concept of a natural ending. PMID- 7775038 TI - Analytic listening and the experience of surprise. AB - The analyst's experience of surprise, its relation to different models of analytic listening and its function in the analytic process is illustrated and explored through a series of clinical vignettes. Surprise is a crucial affective ingredient of the analyst's attention and data-gathering. It is multiply determined and inevitably reflects some discovery or rediscovery on the part of the analyst about both the patient and the analyst. In the dynamic tension of the analyst's listening there is always an interplay between expectation and surprise, as each new facet of the patient's conflictual organisation is revealed. Evenly-hovering attention entails the setting aside of conscious expectation and so maximises the potential for curiosity, surprise and discovery. The author describes the relation of surprise to transient identifications with the patient and to the interventions that result, the relation of surprise to the sense of the uncanny, and the shifts in the analyst's defensive organisation that allow for the experience of surprise. Several vignettes illustrate the interplay of the analyst's and the patient's psychologies and the manner in which surprise may alert the analyst to mutually-created resistances and enactments, which may appear to be discrete phenomena, but are in fact continuous processes, intrinsic to the work. PMID- 7775039 TI - A silenced Indian: more on the secret fantasy of being an exception. AB - By means of some aspects of an analysis, the author shows how the fear of being murdered may form part of the secret fantasy of being an exception. This fantasy should offer protection against being helplessly at the mercy of intense feelings which cannot be integrated, and of an intolerable loss of the sense of self, which renders true separation impossible. During the course of development the fantasy gradually assumes its definitive form. One element of this definitive form is that the analysand exists in a state of adulthood as he imagined it as a child. Control and autonomy here seem guaranteed, and dependence, helplessness and ridiculousness have been overcome. For the creation of such a fantasy, the analysand makes 'a great leap forward' at one or more stages of his development. The author indicates how a leap of this kind could be imagined in intrapsychic terms. PMID- 7775040 TI - Misunderstanding and psychic truths. PMID- 7775041 TI - On the difficulty of making a mutative interpretation. AB - Beginning with Strachey's formulation of the mutative interpretation as the vehicle of the therapeutic action of psychoanalysis, the author considers what makes a mutative interpretation difficult for the analyst. He concludes that this difficulty stems from a relationship of mutual projective identification between patient and analyst, which produces an atmosphere antagonistic to analysis. By viewing the analytic dyad as a group of two, it is possible to relate this anti analytic atmosphere to Freud's and Bion's theories of group mentality. The author also concludes that Strachey's 'auxiliary superego' is indistinguishable in practice from the analyst's ego, since it is concerned only with 'real and contemporary' events, and suggests that our understanding of what is specific to the therapeutic action of psychoanalysis would be simplified and improved if we replaced Strachey's terms 'auxiliary superego' and 'mature superego' with 'ego'. A successful mutative interpretation is a victory of ego over superego; this process requires that the analyst free himself from the intellectual deterioration that the fusion of superegos has produced; and this accomplishes one of the purposes of analysis: to help the patient think and feel what is true. PMID- 7775042 TI - Special issue dedicated to M. Russell Harter. PMID- 7775043 TI - Locating VEP equivalent dipoles in magnetic resonance images. AB - Pattern-reversal and diffuse flash visual evoked potentials (VEPs) were obtained from 4 normal adults. A spatiotemporal dipole model was used to determine the location of the hypothetical equivalent dipoles consistent with the scalp distribution of the VEPs. Equivalent dipoles representing ERG and VEP activity were placed within 3-D magnetic resonance images of the brain. Most of the localization error appeared to be due to inadequate sampling of the potential field in frontal and occipital areas by the 10-20 system of electrode placement. Locating electrophysiologic dipoles within magnetic resonance images of brain structure allows evaluation of dipole localization techniques. PMID- 7775044 TI - Comparison of the smooth eye tracking disorder of schizophrenics with that of nonhuman primates with specific brain lesions. AB - The smooth pursuit eye tracking deficit (ETD) often associated with schizophrenia has generated enormous interest over the last 20 years. The deficit is observed in about 80% of schizophrenics and in half of their first degree relatives. It is not affected by neuroleptic medication and is not due to inattention. A review of 52 studies (and actual records when available) on ETD in schizophrenia reveals that the deficit can consistently be described as low gain pursuit augmented with catch-up saccades and often peppered with intrusive saccades. A review of the brain areas that have been shown to be involved in pursuit provides the necessary background for the subsequent section which details the nature of the smooth tracking deficits following experimental lesions. This section reveals that the ETD following lesions of the frontal lobe is unique in that it closely resembles the ETD of schizophrenics. This finding lends further support for frontal lobe theories of schizophrenia. PMID- 7775045 TI - Reflections on visual evoked cortical potentials and selective attention: methodological and historical. AB - Details of research in which Russ Harter participated in his formative years are reviewed. Harter's participation in the early work on Visual Selective Attention (Eason, Harter & White, 1969) probably contributed most importantly to his career. While reviewing Russ's early experience with basic vision research and pioneer visual evoked potentials (VEPs), there is reference to extensive information regarding stimulus effects on VEPs (exogenous components of the ERP). There can be complex early and late waveforms and waveform changes with changes in certain stimulus conditions. There are critical peripheral vision effects at various loci over the visual field on VEP and reaction time. Special emphasis is given to effects of individual differences in training and skill of experienced subjects, as well differences in ability. These observations may suggest methods for optimizing sensitivity of ERPs and possibly some clues toward further understanding of ERPs. PMID- 7775046 TI - Spatial vision in adults and infants: a tribute to Russell Harter. AB - To be recognized, the retinal image of an object must first be segregated from the retinal image of its surroundings. Luminance contrast is only one way by which an object can be rendered visible. Motion contrast alone, texture contrast alone, colour contrast alone and disparity contrast alone can also render an object visible. This paper notes that psychophysical studies of patients with brain lesions show that motion-defined form and luminance-defined form are processed separately and describes how magnetic (MEG) or electrical (VEP) recording can be used to compare brain responses to luminance-defined form, motion-defined form, colour-defined form, texture-defined form and disparity defined form. At an early stage in visual processing, the retinal images of luminance-defined objects pass through neural filters, each of which is selectively sensitive to a limited range of orientations, spatial frequencies and temporal frequencies. The properties of individual filters can be isolated and quantified by means of the two-sinewave VEP approach. The two-sinewave method also allows binocular function to be tested objectively and its normality assessed quantitatively even when one or both eyes have low acuity. Evoked potential studies of visual development in human infants and studies of labile phenomena in adults are both facilitated by the speed of our VEP sweep method. PMID- 7775047 TI - Comparison of visual evoked potential and psychophysical contrast sensitivity. AB - We measured contrast processing as a function of spatial and temporal frequency using three measurement techniques: psychophysical thresholds, visual evoked potential (VEP) thresholds and VEP amplitudes. Measurements were made using the same stimulus parameters and on the same group of subjects. The agreement among these functions depended upon the particular spatio-temporal stimulus employed and in general, there were more differences than similarities among these measures. For example, VEP derived functions (both amplitude and threshold) peaked at 4 c/deg, whereas, the psychophysical functions peaked at 1 c/deg. VEP amplitude functions were maximum at > or = 3.5 Hz, whereas both psychophysical and VEP sensitivity were maximum at < or = 2.5 Hz. VEP thresholds were broad and low pass in shape and in contrast, the psychophysical and VEP amplitude functions were band pass. In summary, comparisons among these measures of contrast processing must be made with caution. PMID- 7775048 TI - Contrast-dependent responses in the human visual system: childhood through adulthood. AB - Visual evoked potentials (VEPs) to temporal modulation of spatial patterns, recorded from humans ranging in age from 4-42 years, demonstrated that contrast dependent responses exist in early childhood and change dramatically throughout childhood. Bright or dark isolated-check stimuli were used to emphasize contributions from ON or OFF pathways to the VEP. (ON and OFF pathways constitute one major pair of parallel subsystems, which process brightness [positive contrast] and darkness [negative-contrast] information, respectively.) The developmental effects observed for each pathway were similar in magnitude and time course, suggesting maturation of a common physiological mechanism dependent on spatial contrast. Children's responses were more variable and larger than those of adults, and exhibited a relative phase lag. In addition, we recorded transient VEPs to a conventional contrast-reversing checkerboard pattern. The latency of the major positive wave (P100) was found to decrease, while the latency of the initial positive wave (P60) was found to increase, with increasing age. We propose a vector-summation model, which posits a relative decrease in cortical excitation with increasing age, to explain our major findings. PMID- 7775049 TI - Infant visual development: an overview of studies using visual evoked potential measures from Harter to the present. AB - Studies of sensory and perceptual abilities in infants require creative, innovative techniques. Although the young infant's response repertoire may appear limited to the naive individual, a number of highly refined procedures have been developed and implemented with these non-verbal humans over the last twenty years. The most successful protocols for evaluating visual development rely either on behavioral responses or on electrophysiological recordings. The first published report using visual evoked potentials to study the development of pattern vision in human infants was presented by M. Russell Harter. This work provided the impetus for a wealth of studies exploring issues of visual information processing abilities in early infancy. The available range of data and experimental techniques are now sufficiently refined that many clinical issues are currently being addressed. The purpose of this review is to document the evolution of scientific studies since Harter's seminal work. The selection of protocols presented focuses on those with either current clinical applications or those which hold promise for future applications in the evaluation and treatment issues of abnormal visual development. PMID- 7775050 TI - The time-course of global precedence and consistency effects. AB - The global precedence effect refers to the finding that global aspects of a scene are processed more rapidly than local detail in the scene. In experiments with large Hs and Ss (global stimuli) made up of small Hs and Ss (local stimuli), choice reaction time (RT) to the global letters is shorter than RT to the local letters (global precedence effect). In addition, RT for local letters is shorter when the local letters are the same as the global letter (consistency effect). We sought to determine the time course of the global precedence and consistency effects by delaying the global information relative to the local information. In Experiment I, the middle cross-bar of the global letter (S or H) was presented followed by the rest of the global letter at delays of 0, 48, 80, 160, 320 and 640 ms. The results indicated that the global precedence effect was obtained at delays < 48 ms and local precedence effects are obtained at delays > 80 ms. Consistency effects were found in the absence of global precedence effects, but only at delays of 48 and 80 ms. Experiment II was a replication with delays of 16, 32, 48, 64, 80, and 96 ms. The results of this experiment were in agreement with those of Experiment I. These findings offer support for the notion that the consistency effect is mediated by a higher level process than is the global precedence effect. PMID- 7775051 TI - Discriminability of random-dot stereograms in three-dimensional space. AB - The discriminability of crossed-disparity (near) and uncrossed-disparity as a function of their location in the upper-left, upper-right, lower-left, and lower right quadrants of the visual field. Discriminability was assessed using choice reaction-time (RT) and accuracy measures. While near targets were recognized equally well in the upper and lower fields, far targets were perceived more easily in the upper visual field. The discriminability of far targets was particularly poor in the lower left quadrant. These results point to the existence of fundamental asymmetries in perceiving crossed and uncrossed disparities along the vertical and lateral axes. PMID- 7775052 TI - Models of binocular luminance interaction evaluated using visually evoked potential and psychophysical measures: a tribute to M. Russell Harter. AB - We determined subjects' responses to sine-wave modulated lights employing visually evoked potentials (VEPs) and psychophysical thresholds in a series of experiments. The stimuli had the same temporal frequency and mean luminance in each eye but the phase difference between the two eyes was varied so that phase was either the same (dioptic) or different (dichoptic) in the two eyes. The data were fit by a model which had two binocular pathways, one which summed monocular nonlinear elements and a second which had a nonlinearity following the combination of monocular linear elements. In the second channel the outputs of the monocular linear elements were summed at low luminance while at higher luminance levels they were subtracted. Based on variations in the threshold data with temporal frequency, the pathway which summed nonlinear monocular elements was identified with the magnocellular (M) pathway, and the pathway which combined monocular linear elements prior to a binocular nonlinear element was identified with the parvocellular (P) pathway. PMID- 7775053 TI - The role of attention in feature detection and conjunction discrimination: an electrophysiological analysis. AB - An electrophysiological probe technique was used to ascertain whether the same attentional mechanisms are employed for both the detection of simple visual features and the discrimination of conjunctions of features. Visual search arrays containing 14 grey items and 2 colored items were presented; one color was designated relevant for each trial block. Subjects were required to report the presence or absence of the relevant color (feature detection condition) or the shape of the relevantly-colored item (conjunction discrimination condition). Shortly after the onset of the search array, a task-irrelevant probe stimulus was flashed at the location of the relevant or irrelevant color and the event-related potential (ERP) produced by this stimulus was used to assess sensory processing at the probed location. Probes presented at the location of the relevant color were found to elicit enhanced ERP components and probes presented on the opposite side of the display from the relevant color elicited suppressed components. These effects were observed in both the detection and discrimination conditions, indicating that spatially restricted attentional processes are used for both the detection of simple features and the discrimination of conjunctions. However, one ERP component (the PI wave) exhibited these effects in the discrimination condition but not in the detection condition, indicating that conjunction discrimination utilizes additional attentional processes beyond those required for feature detection. PMID- 7775054 TI - Electrophysiological indicants of black-white discrimination performance for letter and non-letter patterns. AB - This study examined event-related potentials (ERPs) and behavioral measures, considered to be sensitive to the selective processing of black versus white letter and non-letter patterns, in a group of seventy-four randomly selected 6 to 8 year old children. Results demonstrated faster and more accurate behavioral performance on the experimental task for the letter than for the non-letter patterns. The ERP measures provided complementary information regarding this letter facilitation effect, indicating that the selective neural processing of letter as compared to non-letter patterns was present in the electrophysiological waveform within the initial 100-140 ms after stimulus presentation. Later ERP measures (200-260 and 500-600 ms post-stimulus) in response to the letter stimuli showed greater differences as a function of task relevance over the left than over the right hemisphere. The results from the present study indicate a remarkably early facilitative influence of stimulus type (letter versus non letter patterns) on the luminance discrimination of these stimuli and are consistent with an overlap of linguistic and perceptual processing. PMID- 7775055 TI - Connectional specificity in the cat's retinogeniculate system. AB - The establishment of normal patterns of retinogeniculate projections in cats is the end-product of the operation of at least three guidance/recognition mechanisms. First, topographic order must be retained in the central maps of visual space. Second, inputs from the two eyes must segregate from each other and target their appropriate layers in the lateral geniculate nucleus. Finally, specific cell classes in the retina must stabilize contacts with functionally matched geniculate neurons. These processes are ordered temporally, and may permit the specification of accurate retinogeniculate connections using a minimum of molecular gradients and markers. PMID- 7775056 TI - Mismatch negativity--a unique measure of sensory processing in audition. AB - Physically deviant auditory stimuli occurring among frequent ("standard") stimuli (e.g., tones or phonetic stimuli) elicit the mismatch negativity (MMN) of the auditory event-related potential (ERP). The MMN is presumably generated by a mismatch process between the sensory input from a deviant stimulus and a neural sensory-memory trace representing the physical features of the standard stimulus. This process, as well as sensory analysis of auditory input and its encoding into the memory trace, appear to be automatic since the MMN is elicited even by changes in unattended auditory stimuli. Therefore the MMN indirectly provides a unique, objective measure of the central representation of a sound. This opens new possibilities for basic research as well as clinical and other applications. PMID- 7775058 TI - Shifting attention in visual space: the effects of peripheral cueing on brain cortical potentials. AB - The effects of attentional shifts following peripheral cues were studied in humans using event-related potentials (ERPs) and reaction times. Subjects released a key following the presentation of a target preceded by a predictive cue in the same (valid) or the opposite (invalid) visual field, or a bilateral, non-predictive cue. The stimulus onset asynchrony (SOA) separating cue and target was either 200 or 600 ms. Subjects were faster and more accurate when responding to validly cued targets. Attentional modulation of the ERP was manifested as an enhancement of P1-N1 amplitude at posterior electrode sites following a validly cued target. Furthermore, the latencies of P1, N1 and P3 were significantly shorter in valid trials than in invalid trials. These results only reached significance with the longer SOA, since ERP refractoriness distorted the response evoked by the target when the SOA was only 200 ms. The findings are discussed in the context of previous behavioral and ERP cueing studies. PMID- 7775057 TI - Event related potentials in adults diagnosed as reading disabled in childhood. AB - The purpose of this study was to identify electrophysiological correlates of reading disability (RD) in adults with psychometrically documented childhood reading histories. Specific a-priori hypotheses for these correlates were generated from the findings of Harter, Anllo-Vento, Wood & Schroeder (1988a); Harter, Diering & Wood (1988b). The subjects were 32 males with normal intelligence and no history of attention deficit disorder or current major psychopathology. Event related potentials were recorded over O1, O2, C3', C4', F3, and F4 to letter stimuli using an intralocation selective attention paradigm. Subjects with RD showed a general reduction in positivity starting at 150 ms and continuing up to 500 ms. The reduced positivity at left central P240 replicated the findings of Harter et al. (1988b) with children. However, adult RD was associated with more diffuse, bilateral reduction in electrophysiological response to all stimuli. A possible relationship between the bilaterality of the neural deficit and the severity of the dyslexia was proposed: that a bilateral deficit may be involved in severe cases. PMID- 7775059 TI - Event-related potential correlates of early processing in normal aging. AB - Auditory event-related potentials were recorded from normal elderly and young adult subjects during simple reaction time and discrimination conditions. In both response conditions, the stimuli were randomly presented, as in an auditory "oddball" paradigm. It was found that NA, an index of early information processing, was significantly delayed in the elderly. Although the latency of N1 was not significantly different between the groups, the latencies of N2 and P3 were significantly longer for the aged subjects. The amplitudes of N1, NA1, NA2 and N2 showed no group differences. The raw amplitude of P3 showed a group difference in topography: Pz was greater than Fz for the young group, but not for the aged. When the amplitudes of NA1, NA2, and P3 were scaled, however, the topography of these components showed no significant group differences. These findings suggest that the age-related slowing of later ERP components and behavior may be partially accounted for by delays in early attention dependent perceptual processes, as indexed by NA. PMID- 7775061 TI - In memory of M. Russell Harter scientist, scholar, educator May 13, 1940-March 24, 1990. PMID- 7775060 TI - Cellular bases for the control of retinogeniculate signal transmission. AB - The dorsal lateral geniculate nucleus (LGN) is the major thalamic relay for retinal signals en route to cortex. However, LGN cells operate as more than just a simple relay of their retinal inputs. Rather, they function as a variable gate, determining what, when, and how much retinal information gets passed to visual cortex. Two factors that are key to this control are the innervation patterns and electrophysiological membrane properties of geniculate cells. This paper discusses three active membrane properties and the manner in which they modulate the transfer of retinal signals to cortex. They are the low threshold calcium (Ca2+) conductance, a transient potassium (K+) conductance, and NMDA receptor mediated excitatory postsynaptic potentials (EPSPs). The low-threshold Ca2+ conductance transforms a geniculate cell from a state of single spike activity to one of bursting discharge, the potassium current leads to a delay in membrane depolarization to reach spike threshold, and NMDA receptor activity modulates EPSP amplitude and duration near spike threshold. Additionally, we consider how nonretinal inputs, such as the ascending cholinergic pathway from the brainstem parabrachial region and the descending pathway from layer VI of visual cortex, influence the expression of these membrane properties through their control of membrane potential. PMID- 7775062 TI - Defining the neural bases of visual selective attention: conceptual and empirical issues. AB - This paper focuses on conceptual and empirical issues relevant to defining the neural bases of visual selective attention. At the most general level, it is held that the integration of human and monkey research is essential to developing a generally applicable, yet precise, understanding of attentional mechanisms. More specific issues that are considered here include: 1) the general definition of attention (as a process, state, etc.) and the operational definition of attention in experimental work, 2) the possibility that different forms of attention use distinctive neural circuits, 3) the levels of the system at which attention may modulate sensory inflow, 4) the degree to which circuits and levels addressed by attentional modulation depend on task (sensory and behavioral) variables and 5) the nature of cellular processes that may underlie attentional modulation. The available techniques for examining neural processes in humans and monkeys are considered in light of these issues and the need for direct comparability between human and monkey experiments. PMID- 7775063 TI - Temporal dynamics of visual-evoked neuromagnetic sources: effects of stimulus parameters and selective attention. AB - Results are reviewed from several neuromagnetic studies which characterize the temporal dynamics of neural sources contributing to the visual evoked response and effects of attention on these sources. Different types of pattern-onset stimuli (< or = 2 degrees) were presented sequentially to a number of field locations in the right visual field. Multiple dipole models were applied to a sequence of instantaneous field distributions constructed at 10 ms intervals. Best-fitting source parameters were superimposed on Magnetic Resonance images (MRI) of each subject to identify the anatomical structure(s) giving rise to the surface patterns. At least three sources, presumably corresponding to different visual areas, were routinely identified from 80-150 ms following the onset of visual stimulation. This observation was consistent across subjects and studies. The temporal sequence and strength of activation of these sources, however, were dependent upon the specific stimulus parameters used to evoke the response (e.g., eccentricity) and on the relevance of the stimulus to the subject. In addition, our results provide evidence for the recurrence of activity in striate and extrastriate regions, following the initial cycle of responses. PMID- 7775065 TI - Circadian differences in hemisphere-linked spelling proficiencies. AB - Male and female adolescents (N = 113) were assigned randomly to spelling instruction in either morning or afternoon groups for a school year. A spelling list (100 words) was administered at the beginning of the school year to obtain a sample of error responses and estimate proficiency. Although equally proficient, subjects tested in the afternoon showed more phonetically inappropriate errors, while those tested in the morning showed more phonetically appropriate errors. This error pattern is viewed as support for a more engaged left hemisphere in the morning. There were no differences on two types of visual errors. Subjects then received instruction in spelling for nine months in either morning or afternoon settings. Time-of-day effects were not evident on the word list and there were too few errors to conduct a posttest error analysis. However, standardized test results for a subgroup revealed that subjects receiving morning instruction made greater gains on phonetically regular words compared to phonetically irregular words--an effect consistent with a circadian-linked higher level of left hemisphere engagement early in the day. The findings are of a pilot nature, but implications for education and further research are discussed. PMID- 7775064 TI - Sex differences in patterns of hemispheric cerebral metabolism: a multiple regression/discriminant analysis of positron emission tomographic data. AB - Sex differences in brain hemispheric structure and function have been reported, and sex-related differences in hemispheric interregional correlations were reported in a prior analysis of resting PET glucose metabolic (rCMRglc) data. To explore further the effect of sex on patterns of hemispheric brain functional interactions, we applied a multiple regression/discriminant analysis to resting rCMRglc PET data from young normal men and women to test two hypotheses: (1) women have stronger between-hemisphere functional interactions; (2) men have stronger within-hemisphere functional interactions. Two separate discriminant functions based on these hypotheses distinguished men and women: the first reflected rCMRglc interdependencies between hemispheres and correctly classified all women and 94% of the men; the second reflected rCMRglc interdependencies within the left hemisphere and correctly classified 82% of the women and 88% of the men. Because the discriminant functions successfully distinguished men and women, these results provide support for both hypotheses. PMID- 7775066 TI - Laser evoked brain potentials in response to painful trigeminal nerve activation. AB - Long latency brain potentials were evoked by infrared laser stimuli (LEPs) applied to the right forehead in order to activate the thinnest cutaneous A-delta afferents of the upper branch of the trigeminal nerve thus inducing a painful sensation. Ten healthy male subjects participated in 4 identical subsequent sessions, one week apart, receiving 4 blocks of 40 stimuli each. This way the individual trigeminal LEPs, as well as their inter- and intraindividual reliability were determined. Five major components could be identified, denoted by polarity and peak latencies: N150, P230, N300, P360, N480. The LEP waveforms were found to be highly stable within subjects, peak latencies varied by less than 5%. Great variation in waveform appeared amongst subjects, peak latencies varied by more than 15%. The last two components exhibited the largest variability and were not identified in all subjects. PMID- 7775067 TI - Conduction velocity groups in the retino-tectal and retino-thalamic visual pathways of the pigeon (Columbia livia). AB - The anatomical characteristics of the avian visual system are well known. However, there are wide gaps in our knowledge with respect to the physiological characteristics of their visual system. For example, we lack both an operational identification of the different ganglion cell types present in the retinae of birds, and a description of their presumptive differential central projections. The results presented here address this latter point by classifying the conduction velocity groups of fibers present in the optic tract of the pigeon. We report the existence of at least 5 groups of axons in the optic tract of the pigeon, with conduction velocities of 22-18 m/s, 12-10 m/s, 8 m/s, 6 m/s and less than 2.5 m/s. All five groups project to the tectum but only the four fastest groups project to the dorsal thalamic complex. The homologies with the populations of retinal axons found in cats are discussed. PMID- 7775068 TI - Chronic & infrequent opioid exposure suppresses IL-2R expression on rhesus monkey peripheral blood mononuclear cells following stimulation with pokeweed mitogen. AB - In the present investigation, infrequent and chronic (daily) exposure of rhesus monkeys to morphine was investigated for their effect on cytokine receptor expression, interleukin (IL)-2-production, and the nuclear factor kappa B (NF kappa B) levels following stimulation with PWM. In a time-dependent manner, peripheral blood mononuclear cells (PBMCs) from both infrequent- and daily morphine treated monkeys displayed significantly less (40 +/- 7%) IL-2 receptor compared to PBMCs from saline-treated controls. However, PBMCs from chronic opioid- and infrequent opioid-treated monkeys displayed similar levels of IL-4 and IL-7 receptors compared to saline-treated animals. Following stimulation with PWM, PBMCs from chronic opioid-treated monkeys produced elevated levels of IL-2 (870 +/- 94 pg/ml) compared to IL-2 levels (463 +/- 88 pg/ml) of PBMCs from saline-treated monkey. Likewise, PBMCs from chronic-morphine exposed monkeys had elevated levels (43%) of NF kappa B compared to PBMCs from saline-treated (control) monkeys following 72 hours in culture with PWM. Collectively, these observations suggest morphine regulates selective molecular events that manifest in biologically altered immune function including T cell activation and IL-2 production. PMID- 7775069 TI - Embryonic cultures but not embryos transplanted to the mouse's brain grow rapidly without immunosuppression. AB - Embryos and embryocultures can be successfully transplanted into various bodily organs. However immunosuppression or homogenicity are required for the success of such experimental manipulation. Since the brain is considered immunologically privileged, we transplanted 2-4 cell embryos of C57BL x BALB/c, embryonic stem cells (ES) or embryoid bodies (EB) cultures into the hippocampus of the heterogeneous mouse stock HS/IBg. Both ES and EB cultures developed into an extensive growth, eventually larger than the brain itself, causing the death of the host in less than 29 days. The growth was identified as teratoma, mostly made of immature cells and tissues of diverse origin. Thus, the overall histological picture was that of a malignant teratoma. On the other hand, no embryos were found at any time after the transplantation; apparently, they could not survive in the host brain. The growth rate and the relative lack of rejection suggest that the brain offers a unique medium for ES and EB cultures but, not to embryos. PMID- 7775070 TI - Metabolic activity in rat visual system during exposure to high and low intensities of patterned and diffuse light. AB - An examination of rat visual system activity, during exposure to either "pattern" (black and white stripes) or "diffuse" (eye covered by white mask) visual stimulation at high or low illumination intensities (1600 and 1 lux at cornea, respectively), was carried out using the 2-deoxyglucose (2-DG) autoradiographic technique. Pattern elevated 2-DG uptake in the dorsal and ventral lateral geniculate nuclei, in the lateral posterior nucleus, and in area 17, but was less effective at the high than at the low light intensity. Diffuse light also elevated 2-DC uptake in the thalamic nuclei but the increase was less impressive and the same at both intensities. Diffuse light at either high or low intensity had no effect on cortex. Like thalamus and cortex, pattern was a less effective stimulus for the colliculus at the high than at the low intensity, but, in contrast to thalamus and cortex, high intensity diffuse light suppressed 2-DG uptake in the colliculus to a level below that produced by darkness; low intensity diffuse light had no effect. These 2-DG findings are discussed in terms of how forebrain and midbrain divisions of the rat's rod-dominated visual system maintained their respective spatial processing and change-detecting functions over a considerable range of illumination intensity. PMID- 7775071 TI - Utilization of maternal perinatal risk indicators in the differential diagnosis of ADHD and UADD children. AB - The purpose of this study was to differentiate between children diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD), children with Undifferentiated Attention-Deficit Disorder (UADD) and a control group using maternal perinatal information. The sample consisted of 74 ADHD, 56 UADD, and 135 normal children between the ages of 6 years, 5 months and 13 years, 4 months. The results supported the use of maternal perinatal information in the diagnosis of attention disorders. More specifically, the greater the number of medical conditions prior or during their pregnancy the more likely a child was diagnosed with an attention deficit disorder. In addition, if the mother experienced moderate emotional stress or smoked cigarettes during pregnancy the child was more likely to be diagnosed with an attention deficit disorder. PMID- 7775072 TI - Weak electromagnetic fields reverse visuospatial hemi-inattention in Parkinson's disease. AB - Drawing tasks, both free and copied, have achieved a central position in neuropsychological testing of patients with unilateral cerebral dysfunction by virtue of their sensitivity to different kinds of organic brain disorders and their ability to provide information on lateralized brain damage. In the drawings of patients with right hemispheric damage, visuospatial neglect is revealed by the omission of details on the side of the drawing contralateral to the hemispheric lesion. Patients with unilateral cerebral damage, particularly those with left hemispheric damage, also demonstrate a tendency to place their drawings on the side of the page ipsilateral to the cerebral lesion, a phenomenon which has been termed visuospatial hemi-inattention. It has been reported previously that brief external application of alternating pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity improved visuoperceptive and visuospatial functions and reversed neglect in Parkinsonian patients. The present communication concerns four fully medicated elderly nondemented Parkinsonian patients (mean age: 74.7 +/- 4.6 yrs; mean duration of illness: 7.7 +/- 5.2 yrs) in whom application of these EMFs produced reversal of visuospatial hemi inattention related to left hemispheric dysfunction. These findings support prior observations demonstrating that pT EMFs may bring about reversal of certain cognitive deficits in Parkinsonian patients. PMID- 7775073 TI - Improvement in short-term visual memory by weak electromagnetic fields in Parkinson's disease. AB - Neuropsychological studies have demonstrated that Parkinson's disease (PD) is associated with various cognitive deficits ultimately leading in about 30% of patients to the development of dementia. These studies have demonstrated also a greater decrement of right hemispheric functions with visuospatial deficits occurring in up to 90% of PD patients. The Rey-Osterrieth Complex Figure (ROCF) Test has been employed in the assessment of right hemispheric functions and particularly for the evaluation of visuoconstructive abilities and short-term visual memory. I have demonstrated recently that external application of electromagnetic fields (EMFs) in the picotesla (pT) range intensity is an effective nonpharmacological modality in the management of the motor and cognitive deficits of Parkinsonism. In the present communication I present 3 fully medicated nondemented PD patients (mean age: 68 +/- 8.1 yrs; mean duration of illness: 9.0 +/- 4.0 yrs; mean disability on the Hoehn and Yahr scale: 3) who were tested on the ROCF Test before and after a series of treatments with EMFs. In response to the administration of EMFs the group demonstrated a mean of 23.1 +/- 13.6% improved performance on copy of the ROCF and a 39.3 +/- 13.4% improvement of short-term recall of the ROCF. These findings demonstrate that treatment with pT EMFs improves deficits in visuospatial functions and visual memory in Parkinsonism which usually remain unaffected during standard treatment with dopaminergic pharmacotherapy. PMID- 7775074 TI - Parkinsonian micrographia reversed by treatment with weak electromagnetic fields. AB - Micrographia is one of the characteristic clinical signs of Parkinson's disease (PD) which is linked to striatal dopaminergic deficiency. It has been reported recently that external application of weak electromagnetic fields (EMFs) in the picotesla (pT) range and of low frequency produced dramatic improvements in motor symptoms in Parkinsonian patients indicating that a specific range of electromagnetic energy increases, among others, striatal dopaminergic neurotransmission. In the present communication, I present two fully mediated Parkinsonian patients who, prior to the application of EMFs, drew lilliputian sized figures reflecting the micrographia of the disease. In both patients a series of treatments with pT EMFs produced, in addition to improvement in motor symptoms, a dramatic increase in the size of their drawings with reversal of their micrographia. Since both patients were maintained on dopaminergic medications prior to and during treatment with EMFs it is suggested that Parkinsonian micrographia is related also to abnormalities of nondopaminergic systems which are affected by weak EMFs. This report corroborates previous observations demonstrating the powerful antiParkinsonian effect of pT range EMFs and highlights the unique efficacy of this treatment modality in Parkinsonism. PMID- 7775076 TI - [Clinical research in Germany]. PMID- 7775075 TI - Cholinergic mechanisms in Gilles de la Tourette's syndrome. AB - Gilles de la Tourette syndrome (GTS), a chronic, familial, neuropsychiatric disorder of unknown etiology, is characterized clinically by the presence of motor and vocal tics that wax and wane in severity over time and by the occurrence of a variety of neurobehavioral disturbances including hyperactivity, self-mutilatory behavior, obsessive compulsive behavior, learning disabilities, and conduct disorder. Pharmacological studies suggest that the tics of GTS result from dysfunction of monoaminergic systems, more specifically from increased dopaminergic activity due to postsynaptic dopamine receptor supersensitivity. However, given that striatal dopaminergic and cholinergic systems exhibit reciprocal antagonism in other movement disorders such as Parkinsonism and chorea, it is conceivable that the cholinergic system is implicated in the disease. In the present communication it is proposed that: (a) the emergence of motor and vocal tics in GTS is associated with increased central cholinergic activity; (b) cholinergic overactivity is involved in the manifestation of other symptoms in GTS including depression, sleep disorders, motion sickness, pain, sensory tics, and the waxing and waning course of the disease; (c) abnormalities of the cholinergic system support previous evidence linking GTS with delayed cerebral maturation in a subset of young patients; and (d) drugs which stimulate cholinergic receptors may exacerbate symptoms of GTS, and as with dopamine agonists, should be avoided in patients with GTS. PMID- 7775077 TI - [Cellular interactions in the vascular wall and mechanisms of action of endothelial factors]. PMID- 7775079 TI - [Molecular regulatory processes in glomerular cells of the kidney]. PMID- 7775080 TI - [Immunology and genetics of rheumatoid arthritis]. PMID- 7775078 TI - [Respiratory insufficiency]. PMID- 7775081 TI - [Non-genomic aldosterone action. A new concept for the mechanism of action of steroids is developed]. PMID- 7775082 TI - [Incretin research in the development of new strategies of diabetes therapy]. PMID- 7775083 TI - [Clinical neuroendocrinology]. PMID- 7775084 TI - [Hypertriglyceridemia and arteriosclerosis. Physiology and pathophysiology of chylomicron catabolism]. PMID- 7775085 TI - [Mechanism of liver damage. Pathogenesis of primary hemochromatosis and auxiliary liver transplantation]. PMID- 7775087 TI - [Molecular mechanisms of hematopoietic stem cell differentiation]. PMID- 7775088 TI - [Cell differentiation and local regulatory systems]. PMID- 7775086 TI - [Immune dysregulation and malignant lymphoma]. PMID- 7775090 TI - [Male phenotype, female genotype. The role of SRY]. PMID- 7775089 TI - [47-year-old patient with pulmonary hypertension, anemia and thrombocytopenia]. PMID- 7775091 TI - [Organic nitrates. I. Mechanism of action and new therapeutic approaches in myocardial ischemia]. PMID- 7775092 TI - [Organic nitrates. II. Dosage and clinical indications]. PMID- 7775093 TI - [Physician practice limits and disposition. Reflections on moderation in determination of physician supply according to Section 102 SGB V]. PMID- 7775094 TI - [Basically, is there a possibility for therapy with ovulation inhibitors in hepatitis C with virus persistence and in the acute stage?]. PMID- 7775095 TI - [Manifestation of thrombocytopenia of 70,000/microliters in a 30-year-old patient with ankylosing spondylitis]. PMID- 7775096 TI - [Paresthesia]. PMID- 7775097 TI - Retinitis pigmentosa and allied diseases. Implications of genetic heterogeneity. PMID- 7775098 TI - The effect of oxygen on vasoformative cell division. Evidence that 'physiological hypoxia' is the stimulus for normal retinal vasculogenesis. AB - PURPOSE: To assess the role of oxygen in normal retinal vasculogenesis. METHODS: A new preparation for studying cytogenesis in retinal wholemounts was developed. Nuclei of dividing cells were labeled with a monoclonal antibody to bromodeoxyuridine (BrdU), and vascular cells were covisualized with Griffonia simplicifolia lectin. The topography and time course of vasculogenic cell division and vessel formation were determined in the kitten retina during normal development and under experimental hyperoxia and hypoxia. RESULTS: During normal development, vasculogenic cell division was maximal at the leading edge of the forming vessels. Normal vessel formation was initially proliferative, and cell division was high. However, after vessel formation occurred, which presumably relieved tissue hypoxia, the mitogenic process was markedly reduced, and many excess capillary segments underwent retraction. The rate of vasculogenic cell division and vessel formation increased when the inner layers of the retina were made avascular after exposure to hyperoxia, and it decreased when there was an increase in inspired oxygen. CONCLUSIONS: The authors have shown that between 17% and 45% oxygen, the extent of vasculogenic cell division is inversely proportional to the level of oxygen in the inspired gas mixture. They have further shown that dividing vascular cells have a peak density in a region proximal to the edge of the forming vasculature. The density is maximal between P7 and P8, a time when formation of photoreceptor outer segment begins, only a few days before the onset of retinal function. These results led the authors to conclude that the stimulus for normal vasculogenesis is a transient but physiological level of hypoxia induced by the increasing activity of retinal neurons. PMID- 7775099 TI - Supplemental oxygen therapy. Basis for noninvasive treatment of retinopathy of prematurity. AB - PURPOSE: To determine the effectiveness of supplemental oxygen therapy (SOT) in ameliorating the proliferative vasculopathy characteristic of the feline model of retinopathy of prematurity (ROP). METHODS: Kittens were exposed to high (70% to 80%) oxygen for the first 4 days of life to induce obliteration of the retinal circulation. The level of inspired oxygen at successive stages after hyperoxia were varied systematically, and the retinas were examined for the extent of revascularization, astrocyte survival, intactness of the blood-retinal barrier, and extent of preretinal vessels. RESULTS: The level of inspired oxygen required to protect the retina from hypoxic damage and yet provide a stimulus for growth of the vasculature varied during a 6-week period. The rate of revascularization of the retina increased as the oxygen content of the inspired gas mixture decreased, with a consequential increase in the pathology observed. However, a regimen that produced a quicker rate of revascularization with a slightly higher level of pathology actually offered the retina greater protection in the long term. The formation of preretinal vessels was effectively prevented by SOT. Supplemental oxygen therapy could be terminated once a significant portion of the retina was revascularized. CONCLUSIONS: The proliferative vasculopathy of a kitten model of ROP can be significantly reduced by a regimen of SOT, which attempts to mimic physiological levels of hypoxia in the retina during its revascularization. Optimal revascularization requires a balance between the rate and quality of vessel growth. With further refinement of the protocol, SOT could provide noninvasive treatment of ROP in neonates. PMID- 7775100 TI - Effect of group B streptococcal meningitis on retinal and choroidal blood flow in newborn pigs. AB - PURPOSE: To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age). METHODS: Fourteen study animals injected with 0.5 ml heat-killed GBS (10(9)) were compared to 10 control animals injected with 0.5 ml saline. The site of injection for both groups was the cerebral lateral ventricles. RetBF and ChBF were measured by radioactive microspheres (141Ce, 51Cr, 113Sn, 85Sr, 95Nb, 46Sc) over a mean arterial blood pressure (MABP) range of 20 to 150 mm Hg. Hypertension and hypotension were induced 2 hours apart in random sequence on each animal by inflating balloon tipped catheters placed at the descending aorta and the aortic root, respectively. RetBF and ChBF were measured 15 minutes before and after injection of GBS or saline (baseline) and during hypotension or hypertension. RESULTS: Fifth-order polynomial regression analyses of RetBF and ChBF (ml/100 g per minute) versus MABP showed that in control animals, blood flows were constant at MABP of 60 to 110 mm Hg for RetBF and was pressure passive above and below these ranges. However, no autoregulation was observed for ChBF throughout the MABP range. In contrast, RetBF of GBS-treated animals increased with increasing blood pressure throughout range of MABP studied, and absence of autoregulation was maintained in the choroid. Vascular resistance (mm Hg/ml per minute/100 g) increased as MABP was raised to maintain constant flow and was correlated linearly with MABP at 60 to 110 mm Hg (r = 0.6682, P = 0.0003) in RetBF of control animals but not in GBS-treated animals (r = -0.291, P = NS). Vascular resistance did not change with MABP for ChBF of control animals (r = -0.264, P = NS) but decreased as MABP was raised in GBS-treated animals (r = -0.548, P < 0.0001). GBS did not alter oxygen delivery, which varied directly with MABP in control animals (RetBF: r = 0.74, P < 0.001; ChBF: r = 0.68, P < 0.001) and in GBS-treated animals (RetBF: r = 0.55, P < 0.001; ChBF: r = 0.68, P < 0.001). CONCLUSION: Group B streptococcal meningitis significantly impairs eye blood flow autoregulation and may contribute to increased risk of retinal damage in infants with meningitis. PMID- 7775101 TI - Local response of the primate retinal microcirculation to increased metabolic demand induced by flicker. AB - PURPOSE: To study the response of the macular circulation to a local increase in metabolic demand created by a flickering source of illumination. METHODS: Laser targeted angiography (release of a fluorescent dye from heat-sensitive liposomes using a laser pulse) was used to study, in subhuman primates, changes in hemodynamic parameters of the retinal circulation that were induced by a flickering source of illumination. Changes in the macular macrocirculation were compared with those in the macular microcirculation and were evaluated at various distances from the foveola. RESULTS: In response to monochromatic light flicker, the blood flow in retinal arteries increased by 30%. The response of the microcirculation was not homogeneous. It showed a maximum increase in the mid perifoveal region where there is an increase in ganglion cells and nerve fibers. Interestingly, the maximum change in the index representing capillary blood flow exceeded the blood flow change in the artery (P < 0.08). CONCLUSIONS: A stimulus expected to cause increased metabolic demand results in a regulatory response by the retinal microcirculation. This response shows spatial variations that correspond with known variations in retinal anatomy. The authors propose that a redistribution of blood can occur between the capillary layers to fulfill high metabolic demands by neuronal tissue remote from the choroid. PMID- 7775102 TI - Variability in choriocapillaris blood flow distribution. AB - PURPOSE: To investigate variability of choriocapillaris blood flow patterns. METHODS: After the intravenous injection of indocyanine green, angiograms were recorded at 30 images per second in rhesus monkey eyes using a fundus camera equipped with a pulsed laser diode light source, synchronized with a gated (5 msec), intensified charge-coupled device, or CCD, video camera. Images of choriocapillaris filling alone were extracted. Plastic corrosion casts were made of two of the monkey's choroidal vasculatures for subsequent scanning electron microscopy examination. RESULTS: Pulsed laser indocyanine green fluorescence excitation produced better definition of choriocapillaris filling than had been achieved using continuous illumination. No correlation was found between the choriocapillaris plexus architecture revealed by the plastic corrosion casts and the observed choriocapillaris lobular filling. Overall posterior pole choriocapillaris dye-filling patterns were relatively stable for periods of days, but they changed gradually for periods of weeks. Localized minor pattern changes occurred on a much shorter time scale. Choriocapillaris filling patterns were altered by acutely elevating intraocular pressure, by O2 and CO2 breathing, and by argon laser retinal photocoagulation of adjacent areas. CONCLUSIONS: Choriocapillaris filling patterns appear to be determined by the network of perfusion pressure gradients that exist among the interspersed feeding arterioles and draining venules connected to the choriocapillaris plexus. Changes in intraocular pressure and in blood PO2 and PCO2 levels can produce marked changes in the distribution of choriocapillaris blood flow. Retinal laser photocoagulation of adjacent fundus areas alters choriocapillaris blood flow to the extent that the altered flow might be an important factor in the beneficial results attributed to retinal laser treatment. PMID- 7775103 TI - Primate rod and cone photoreceptors may differ in glucose accessibility. AB - PURPOSE: Glucose is crucial for the function of retinal photoreceptors, other retinal neurons, and glial cells. Exogenous glucose can be extracted from the retinal and choroidal circulation, and endogenous glucose may be generated from breakdown of intracellular glycogen stores. Because glucose deprivation is a critical component of retinal ischemia, the authors sought to determine the sites of glucose entry into and generation within the retina. METHODS: The localization of the glucose transporter, GluT-1, and the brain and muscle isozymes of glycogen phosphorylase, GlyP, was studied by immunohistochemistry of adult human and monkey retinas. RESULTS: Brain glycogen phosphorylase (B-GlyP) immunoreactivity was found in cone, but not rod, photoreceptors. There was immunostaining of foveal and peripheral cones throughout the cytoplasm from the outer segment to the synaptic pedicle. Short wavelength ("blue") cones were positive for B-GlyP. Diffuse staining of the inner and outer plexiform and the nerve fiber layers did not resemble the distinct morphology of Muller cells. Immunoreactivity to muscle GlyP (M-GlyP) was confined to selected synaptic layers of the inner plexiform layer in monkey retina. Staining with antibody to GluT-1 demonstrated diffuse reactivity throughout the retina, including the blood-retinal barrier cells, retinal pigment epithelium, and vascular endothelium. Ultrastructural immunohistochemistry showed staining of rod and cone inner and outer segments. CONCLUSIONS: These immunohistochemical studies indicate that rod and cone photoreceptors have the biochemical capability to transport exogenous glucose from the circulation. Only cones appear capable of using endogenous glycogen stores. These findings imply that cones could be more resistant to acute reductions in circulating glucose during hypoglycemia. However, during hypoxic insult, glycogenolysis and anaerobic glycolysis could result in increased production of intracellular lactic acid, potentially predisposing the cone to acidotic damage. PMID- 7775104 TI - Phagocytosis and H2O2 induce catalase and metallothionein gene expression in human retinal pigment epithelial cells. AB - PURPOSE: Reactive oxygen intermediates have been implicated in the aging process and degenerative diseases of the eye, including retinopathy of prematurity, cataractogenesis, and macular degeneration. The purpose of this study was to investigate the effect of phagocytosis of photoreceptor outer segments and the addition of exogenous H2O2 on catalase and metallothionein expression in human retinal pigment epithelial cells. METHODS: Confluent RPE cells were treated with bovine photoreceptor outer segments or H2O2 for either 6 or 18 hours. Slot blot hybridization was used to assess catalase and metallothionein gene expression after 6 hours. Catalase enzyme activity and metallothionein content were measured after 18 hours. RESULTS: Phagocytosis or the addition of H2O2 increased catalase enzyme activity and metallothionein twofold above control levels. The addition of n-acetyl cysteine abrogated the inductive effect caused by either stress. Catalase and metallothionein gene expression, measured by slot blot hybridization, also were measurably induced by either stress. Phagocytosis of photoreceptor outer segments increased extracellular H2O2 concentration nine times above control. CONCLUSIONS: The response of the retinal pigment epithelial cells to phagocytosis was indistinguishable from the response observed after the addition of exogenous H2O2. The generation of H2O2 during phagocytosis may act as an intracellular signal in retinal pigment epithelial cells that leads to increased levels of key antioxidant enzymes and other proteins important for protecting the cells from oxidative damage. PMID- 7775105 TI - Regulation of proliferation and photoreceptor differentiation in fetal human retinal cell cultures. AB - PURPOSE: To examine whether fetal human retinal cells can be maintained in vitro over long time periods and to determine whether exogenous growth factors can be used to generate large numbers of photoreceptors within these cultures. METHODS: Fetal human retinas (6 to 13 weeks after conception) were dissected, dissociated, and plated into culture wells. Specific growth factors and steroid/thyroid hormones, which have been shown to influence retinal progenitor cell proliferation and differentiation in rats, were added to the culture medium to determine whether any of these factors had similar effects on human retinal cells. RESULTS: Fetal human retinal cells survived and continued to proliferate for up to 300 days in vitro. Under control conditions, 15 million cells were generated from an initial plating of 100,000 cells; however, the addition of either epidermal growth factor or basic fibroblast growth factor stimulated proliferation and resulted in the generation of more than 100 million cells. A percentage of these cells was induced to differentiate as photoreceptors by adding either retinoic acid or triiodo-thyronine to the culture medium. CONCLUSIONS: Fetal human retinal cells can be maintained and expanded in vitro, indicating that this technique may be useful for generating large numbers of retinal cells. The number and types of cells generated can be influenced by adding exogenous factors to the culture medium. The response of human retinal cells to growth factors and hormones is similar to the response of rodent retinal cells to the same factors, suggesting that the effects of these factors are conserved across species. PMID- 7775106 TI - Age-related variation in the hydraulic conductivity of Bruch's membrane. AB - PURPOSE: To determine whether alterations in local fluid dynamics are associated with aging of the Bruch's membrane-choroid complex. In the macula, such changes have been postulated as causative factors underlying some pathologic manifestations of age-related macular degeneration (AMD). METHODS: The pressure induced flow of physiological buffer through isolated human Bruch's membrane choroid complex was measured using a modified Ussing chamber. Values of flow facilitated the calculation of hydraulic conductivity (flow per unit pressure), for individual complexes, which subsequently allowed for the development of an age-related profile. RESULTS: In all specimens, flow across the Bruch's membrane choroid complex was found to be directly proportional to the applied pressure, whereas hydraulic conductivity was independent of pressure over the range studied. The hydraulic conductivity of the complex exhibited an exponential decrease with increasing age of donor, the most rapid decline occurring during the first four decades of life. The age-related change was most pronounced in the macula, where hydraulic conductivity halved every 9.5 years, compared to a t1/2 for the periphery of 19 years. CONCLUSIONS: The decline in the hydraulic conductivity of the Bruch's membrane-choroid complex with age implies a decreased capacity for the exchange of fluid between the choroidal and retinal pigment epithelial compartments. The relevance of these findings to the development of AMD is discussed. PMID- 7775107 TI - Albumin movement out of the subretinal space after experimental retinal detachment. AB - PURPOSE: The subretinal fluid of serous retinal detachments contains protein, but little is known about its origin and fate. The authors designed experiments to study the rate and route of albumin movement out of the subretinal space. METHODS: Experimental retinal detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution containing serum levels (approximately 30 mg/ml) of fluorescein isothiocyanate (FITC) albumin into the subretinal space through a micropipette. Subretinal, vitreous, and serum fluid samples were withdrawn 0 to 4 hours later through a similar micropipette and were analyzed for osmolality, FITC albumin content (by fluorophotometry) and FITC+native albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). RESULTS: Albumin injected into the subretinal fluid diffused steadily into the vitreous, and its concentration decreased by approximately 5% per hour. This rate was unaffected by RPE damage. Albumin did not move into the bloodstream unless the RPE was damaged with sodium iodate, and then it crossed the RPE at approximately 25% of the rate at which it moved into the vitreous. Subretinal fluid osmolality remained within the range of 293 to 294 mOsm/kg despite protein movement and the continual absorption of fluid from the detachments. CONCLUSIONS: These results show that albumin in the subretinal space diffuses readily into the vitreous, and subretinal osmolality changes are rapidly equilibrated with the vitreous. Albumin does not cross normal RPE, and it crosses iodate-damaged RPE more slowly than it crosses retina. Thus, there must be a constant supply of albumin if high subretinal concentrations are to be sustained in clinical serous detachments. PMID- 7775108 TI - Identification and synthesis of chemotactic tripeptides from alkali-degraded whole cornea. A study of N-acetyl-proline-glycine-proline and N-methyl-proline glycine-proline. AB - PURPOSE: To identify and synthesize the polymorphonuclear leukocyte chemoattractant(s) released from alkali-degraded corneas. METHODS: Corneas were degraded in 1.0 N NaOH, neutralized, ultrafiltered, and dialyzed. The final active ultrafiltrate was subjected to high-performance liquid chromatography on a Protein PAK I-60 column. The most active fractions were further separated on a mu Bondapak-C18 and I-60 column in sequence. RESULTS: Fraction 38 from the final I 60 column associated with a 210-nm absorption peak and elicited a polarization and chemotactic response from polymorphonuclear leukocytes. The loss of polarization activity in fraction 38 after exposure to prolidase suggests that this peptide contains a Pro-X (X = amino acid) peptide bond. The amino acid composition of fraction 38 was 35% glycine and 53% proline. Peptide sequence analysis was unable to establish a primary sequence even though Picotag analysis showed the presence of large amounts of the two amino acids. Mass spectrometry revealed only two molecular species of 312 MWt and 284 MWt. Tripeptides were synthesized using all possible amino acid permutations of 2 Pro and 1 Gly and tested in the polarization and chemotactic assays. These techniques demonstrated that n-acetyl-Pro-Gly-Pro, and to a lesser degree n-methyl-Pro-Gly-Pro, were the only synthetic tripeptides with activity similar to the purified chemoattractant. CONCLUSIONS: The data show that the chemotactic peptides, purified from alkali degraded whole cornea and confirmed with identical synthetic tripeptides, are N acetyl-Pro-Gly-Pro and N-methyl-Pro-Gly-Pro. Although a number of proteins contain the Pro-Gly-Pro sequence, large amounts of collagen in the cornea suggest this as a major source. The small size and hydrophilic nature of these chemoattractants are predictive of a high degree of diffusibility. These chemoattractants are likely to play a major role in the early neutrophil response after an alkali injury. PMID- 7775109 TI - NaK-ATPase pump sites in cultured bovine corneal endothelium of varying cell density at confluence. AB - PURPOSE: The driving force for ion and water flow necessary for efficient deturgesence of the corneal stroma resides in the ouabain-sensitive sodium (Na) pump of corneal endothelial cells. Using a cell culture model of corneal endothelial cell hypertrophy, the authors examined the expression of Na pumps at the cell surface to see how this central element of the endothelial pump changed as corneal endothelial cell density decreased to a level associated with corneal decompensation in vivo. METHODS: 3H-ouabain binding to NaK-ATPase at saturating conditions was used to quantitate the number of Na pump sites on cultured bovine corneal endothelial cells as the confluent density decreased from approximately 2750 cells/mm2 to approximately 275 cells/mm2. RESULTS: The mean number of Na pump sites per cell at confluence (1.92 +/- 0.07 x 10(6)) did not change as the cell density decreased 2.7-fold from 2763 cells/mm2 to 1000 cells/mm2. However, pump site expression doubled to approximately 4 x 10(6) sites/cell as the cell density decreased from 1000 cells/mm2 to 275 cells/mm2. Despite the incremental increase in Na pump site expression that occurred as the cells hypertrophied below a density of 1000/mm2 to achieve confluence, this increase was insufficient to prevent a decrease in Na pump site density of the intact monolayer, expressed as pump sites/mm2. CONCLUSION: The confluent cell density of cultured bovine corneal endothelial cells can be varied from that found in the normal native cornea to that associated with corneal decompensation. In confluent cultures with cell densities ranging from 2750 cells/mm2 to 1000 cells/mm2, the number of pump sites per cell remains relatively unchanged. Below cell densities of 1000 cells/mm2, the number of pump sites per cell progressively increases. The increased Na pump site abundance in markedly hypertrophied endothelial cells cannot adequately compensate for the progressive reduction in the number of transporting cells per unit area within the intact monolayer. Even when considered with the decrease in the size of the paracellular ion conductive pathway that is a consequence of progressive endothelial hypertrophy, the overall pumping capacity of the intact endothelial monolayer declines. PMID- 7775110 TI - Neural network classification of corneal topography. Preliminary demonstration. AB - PURPOSE: Videokeratography is a powerful tool for the diagnosis of corneal shape abnormalities. However, interpretation of the topographic map is sometimes difficult, especially when pathologies with similar topographic patterns are suspected. The neural networks model, an artificial intelligence approach, was applied for automated pattern interpretation in corneal topography, and its usefulness was assessed. METHODS: One hundred eighty-three topographic maps were selected and classified by human experts into seven categories: normal, with-the rule astigmatism, keratoconus (mild, moderate, advanced), postphotorefractive keratectomy, and postkeratoplasty. The maps were divided into a training set (108 maps) and a test set (75 maps). For each map, 11 topography-characterizing indices calculated from the data provided by the TMS-1 videokeratoscope, plus the corresponding diagnosis category, were used to train a neural network. RESULTS: The correct classification was achieved by a trained neural network for all 108 maps in the training set. In the test set, the neural network correctly classified 60 of 75 maps (80%). For every category, accuracy and specificity were greater than 90%, whereas sensitivity ranged from 44% to 100%. CONCLUSIONS: With further testing and refinement, the neural networks paradigm for computer assisted interpretation or objective classification of videokeratography may become a useful tool to aid the clinician in the diagnosis of corneal topographic abnormalities. PMID- 7775111 TI - Epithelial regeneration after limbus-to-limbus debridement. Expression of alpha enolase in stem and transient amplifying cells. AB - PURPOSE: To examine the expression of the glycolytic enzyme alpha-enolase after limbus-to-limbus epithelial debridement in the rabbit. METHODS: Corneas were debrided, leaving limbal epithelium intact, and were allowed to heal from 2 days to 8 weeks. Immunofluorescence microscopy was used to observe the expression of alpha-enolase. To quantitate changes in alpha-enolase levels 2 days to 4 weeks after wounding, epithelium was harvested, homogenized, and assayed using anti alpha-enolase in immunoslot blots. RESULTS: Expression of alpha-enolase appeared to increase in the limbus and the central cornea during epithelial migration (2 day time point) with intense labeling of all basal cells. These levels were maintained until wound closure (1 week). By 2 weeks, expression in the limbal basal cells decreased to levels present in unwounded corneas. Expression in the corneal epithelium decreased after 2 weeks, progressing from central cornea to the periphery. At 4 weeks, antibody binding decreased concomitantly with a change in the shape of the basal cells from flattened or ovoid to columnar. At 8 weeks, expression of alpha-enolase was similar to that in control corneas. Immunoslot blot data indicated that alpha-enolase made up 0.28% of the total soluble protein in unwounded corneal epithelium and 0.73%, 1.22%, 0.96%, and 0.49% at 2 days, 1 week, 2 weeks, and 4 weeks after debridement, respectively. CONCLUSIONS: These data indicate that expression of alpha-enolase is elevated during corneal epithelial migration initiating from the stem (limbal basal) cell population and that expression is linked to active migration. Furthermore, it appears that limbal basal cells are metabolically active during the period of epithelial sheet movement, whereas peripheral corneal basal cells remain activated as long as 4 weeks after wounding. PMID- 7775112 TI - Systemic immunization with Hsp60 alters the development of chlamydial ocular disease. AB - PURPOSE: To determine whether immunization with recombinant Hsp60 would exacerbate ocular pathology on challenge with viable chlamydial elementary bodies. METHODS: Guinea pigs were immunized either subcutaneously with recombinant Hsp60 or both subcutaneously with recombinant Hsp60 and ocularly with attenuated Salmonella typhimurium expressing the guinea pig inclusion conjunctivitis (GPIC) Hsp60 antigen. All animals were challenged in the conjunctiva with the agent of GPIC, and the degree of gross ocular pathology was determined. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers to Hsp60 were measured in ocular secretions as a measure of the degree of immunization. RESULTS: In primary and challenge GPIC infection, the degree of gross ocular pathology was lower in the immunized group. The presence of high IgA and IgG antibody titers to Hsp60 in tears suggested that the response may have been modified by the presence of blocking antibodies that either may have removed the antigen quickly or prevented interaction with sensitized T cells. In contrast to subcutaneous immunization, the combined immunization regimen, consisting of subcutaneous recombinant Hsp60 followed by ocular inoculation of the attenuated Salmonella, resulted in no difference in gross pathology after reinfection of guinea pigs with GPIC. CONCLUSIONS: These data indicated that the immunization with Hsp60 did not produce exacerbated disease on challenge with viable organisms; however, the data suggested that the route of administration, form of antigen, or both may be critical in the disease process. PMID- 7775113 TI - Protection against herpes simplex virus-induced eye disease after vaccination with seven individually expressed herpes simplex virus 1 glycoproteins. AB - PURPOSE: To compare the efficacy of each of seven expressed herpes simplex virus 1 (HSV-1) glycoproteins as vaccines to protect against ocular disease after primary ocular HSV-1 infection. METHODS: Mice were vaccinated three times with equal amounts of each of seven individually expressed HSV-1 glycoproteins (gB, gC, gD, gE, gG, gH, and gI) and then ocularly challenged with McKrae, a corneal disease-producing strain of HSV-1. Viral clearance from the eye, blepharitis, keratitis, and neovascularization were determined at various times after infection. RESULTS: Mice vaccinated with gD or gB had the best protection against eye disease. Vaccination with gI, gC, or gE produced moderate protection against eye disease. Vaccination with gG produced less protection, and vaccination with gH produced no apparent protection against eye disease. CONCLUSIONS: These results suggest that when used as vaccines, different HSV-1 glycoproteins provide different levels of protection against HSV-1-induced eye disease. Based on comparison with the authors' previously published results, the ability of each glycoprotein to protect against eye disease correlated with the ability of the glycoprotein to induce high serum neutralizing antibody titers and killer cell activity. Results suggest that the effectiveness of these seven glycoproteins in protecting against eye disease can be ranked as follows: gD > gB > gI > (gC = gE) > gG > gH. PMID- 7775114 TI - Measurement of blood-retinal barrier breakdown in endotoxin-induced endophthalmitis. AB - PURPOSE: Endophthalmitis is a severe inflammatory disorder with profound visual consequences. Treatment of this disorder has been limited by the lack of quantitative information regarding retinal responses to severe inflammation. The purpose of this study was to measure the effect of endotoxin-induced endophthalmitis on blood-retinal barrier (BRB) function in vivo using contrast enhanced magnetic resonance imaging (MRI). METHODS: Endophthalmitis was produced by injecting Escherichia coli endotoxin into the midvitreous of pigmented rabbits. Contrast-enhanced MRI was performed at selected intervals thereafter. In all cases, a clinical grading system was used to assess the severity of inflammation before imaging. In a dose-response experiment, total vitreous protein was measured from vitreous specimens obtained 1 day after endotoxin injection and immediately after the imaging procedure. RESULTS: At 1 day after injection, endotoxin produced a selective breakdown of the inner BRB at all doses evaluated (0.01 microgram to 500 micrograms). Permeability-surface area product normalized to the area of leaky retina (PS') increased from 1.35 +/- 0.78 x 10( 4) cm/minute (mean +/- SEM, n = 4 eyes) at a dose of 0.01 microgram to 8.15 +/- 2.22 x 10(-4) cm/minute n = 4) eyes) at a dose of 10 micrograms. Inner BRB integrity was restored by day 28 after injection. In general, changes in PS', blood-aqueous barrier leakage, mean clinical score, and vitreous protein concentration were found, but the correlation between any two of these parameters was poor. CONCLUSION: Leakage of contrast appears early in the course of endotoxin-induced endophthalmitis and is a self-limited process. In future studies, these quantifiable changes in BRB permeability should prove useful in the assessment of various therapeutic interventions. PMID- 7775115 TI - In vivo bacterial protease production during Pseudomonas aeruginosa corneal infection. AB - PURPOSE: To establish if active pseudomonal proteases are present in vivo during corneal infection with Pseudomonas aeruginosa and to determine if the mouse strains used in these and previous studies have the ability to mount a nonocular antibody response to the purified proteases because antibodies to the bacterial proteases were not detected previously during in vivo ocular infection. METHODS: At certain times after corneal infection with P. aeruginosa, corneas were harvested and supernatants from the corneal homogenates were analyzed for proteolytic activity by zymography and immunoreactivity by immunoblotting. The efficiency of the extraction procedures used in these studies was determined by incubating uninfected corneal homogenates with the purified proteases. The resultant supernatants were analyzed for alkaline protease and elastase activity. Additionally, mice were immunized intraperitoneally with the purified proteases with and without adjuvant to determine if the animals could mount a nonocular antibody response. RESULTS: Corneas infected with P. aeruginosa demonstrated the presence of alkaline protease, but not elastase, by the two methods examined. The kinetics of the in vivo alkaline protease response closely parallels previously reported bacterial clearance studies in that peak alkaline protease activity was detected in corneal tissue when peak bacterial numbers also were observed in the eye, and it was absent when the eyes were sterile or nearly sterile. In addition, C57BL/6J mice were capable of mounting a nonocular antibody response to microgram quantities of both proteases only in the presence of adjuvant. CONCLUSIONS: In the model described, enzymatically active alkaline protease, but not elastase, was demonstrated in corneal tissues during in vivo infection. Concentrations of these proteases were much lower than those required to stimulate an antibody response. PMID- 7775116 TI - Freeze-fracture studies of interendothelial junctions in the angle of the human eye. AB - PURPOSE: The aim of this study was to determine the structure and complexity of the intercellular junctions between trabecular endothelial cells and Schlemm's canal endothelial (SCE) cells as they exist in the normal human eye. Despite the probable relevance of these junctions to aqueous outflow, examination of these junctions has been limited to monkey eyes. METHODS: Human eyes (< 24 hours after death) were fixed by immersion in modified Karnovsky's fluid. Radially oriented tissue-chopper sections (190 microns) were trimmed to contain only the trabecular meshwork, Schlemm's canal, and a narrow strip of the sclera. Specimens were processed for conventional electron microscopy and freeze-fracture. Replicas were produced in a freeze-fracture apparatus operated at -115 degrees C and 10(-7) torr. Thin sections were stained with uranyl acetate and lead citrate. Micrographs were taken on a transmission electron microscope. RESULTS: The trabecular endothelial cells were joined by gap junctions and short discontinuous junctional strands that partitioned predominantly with P-face. The strand pattern varied from short and isolated undulating strands to radiating arrays of short junctional strands. No continuous zonulae occludentes were observed. The SCE cells were joined by continuous tight junctions (tj) composed of discontinuous strands that rarely branched or anastomosed. The tj strands fractured preferentially with the E-face, where they were positioned at the bases of shallow valleys. On the P-face, a complementary system of shallow ridges was observed with few particles at their crests. Often, only a single continuous strand was present for long distances, with occasional short discontinuous strands running parallel to the single strand. Less often, short lengths of remarkably complex junctions, which occasionally branched or anastomosed, were also encountered. When more than one strand was present, numerous free endings and transjunctional pathways, described in monkey eyes as "slit-pores," were evident. CONCLUSION: The overall structure of the junctions between endothelial cells of Schlemm's canal in the human eye was more complex, and thus less permeable, than that reported in the monkey eye. The role of slit-pores and other junctions of SCE and trabecular endothelial cells will require further investigation under conditions of flow and in glaucoma to determine if these junctions change in a manner that might influence outflow resistance. PMID- 7775117 TI - Glaucomatous visual fields. FASTPAC versus full threshold strategy of the Humphrey Field Analyzer. AB - PURPOSE: This study examined how FASTPAC, a fast strategy for the Humphrey Field Analyzer (HFA), compares to the standard 4/2-dB full threshold strategy in patients with glaucoma. METHOD: The author tested one eye each of 50 patients with glaucoma (23 with only relative defects, 27 with at least one absolute defect; age range, 25 to 79 years; median age, 61.5 years) with both strategies using program 30-2 of the HFA (stimulus size III). Global visual field indices as calculated by Statpac, unweighted mean sensitivity, and examination time were compared. In addition, a point by point analysis of the sensitivity values was performed. RESULTS: Between the two strategies, no significant differences were found for indices directly related to the sensitivity values (mean sensitivity [MS], mean deviation [MD]) or for the actual thresholds. For the entire population, FASTPAC showed higher mean short-term fluctuation (SF; P = 0.018), lower mean pattern standard deviation (PSD; P = 0.006), and mean corrected PSD (CPSD; P < 0.001) values and a time reduction of more than 30% (P < 0.001) compared to the standard strategy. These differences between the strategies were found to be independent of the amount of field loss, except for PSD (P = 0.001). No age influence was present. Statistically significant linear regression (r > 0.70, P < 0.001) was found between the FASTPAC values of MS, MD, PSD, CPSD, and the corresponding values determined with the standard strategy. No correlation exists for SF (r < 0.46, P > 0.030). CONCLUSIONS: FASTPAC provides a considerable time reduction at the cost of higher threshold fluctuation. This may lead to problems in detecting relative defects or changes in differential light threshold in follow-up examinations. PMID- 7775118 TI - The statistical interpretation of blue-on-yellow visual field loss. AB - PURPOSE: To evaluate short-wavelength-sensitive perimetry in the detection of glaucomatous field loss. METHODS: The sample consisted of 27 normal subjects, 24 patients with primary open angle glaucoma (POAG), and 27 patients with ocular hypertension (OHT). Blue-on-yellow (B-Y) and standard (W-W) perimetry was undertaken with a modified Humphrey Field Analyzer 640 on one eye of each subject and patient. The B-Y data were corrected for individual ocular media absorption. Results were compared to an age-matched normal database of 50 subjects (age range, 60 to 82 years; mean age, 70.0 years; SD, 6.4 years). Visual field indices and total and pattern deviation probability maps were calculated for both W-W and B-Y fields. RESULTS: The B-Y normal database exhibited increased between-subject variability compared to the W-W normal database (P < 0.001). The greater variability increased with the increase in eccentricity (P < 0.001) and with the increase in age (P = 0.032). All patients with POAG exhibited B-Y field loss; 11 demonstrated greater B-Y loss than the corresponding W-W field. In advanced POAG, the B-Y and the W-W fields were similar. Twenty-five of the 27 normal subjects exhibited normal B-Y fields. Five of the 27 patients with OHT manifested B-Y focal abnormality and a normal W-W field: in two, W-W focal loss subsequently developed. CONCLUSIONS: Short-wavelength-sensitive perimetry can identify visual field loss before that detected by W-W perimetry. However, the increased between subject variability necessitates stringent statistical analysis in the definition of abnormality. PMID- 7775119 TI - Transforming growth factor-beta induces plasminogen activator inhibitor type-1 in cultured human orbital fibroblasts. AB - PURPOSE: The level of constitutive plasminogen activator inhibitor type-1 (PAI-1) expression in cultured human orbital fibroblasts is considerably lower than that found in dermal fibroblasts. This divergence in PAI-1 expression implies differences in the pericellular proteolytic environment and, therefore, in the turnover of extracellular matrix. In this article, the authors examine the effect of transforming growth factor-beta (TGF-beta) on PAI-1 expression in orbital fibroblasts. METHODS: Human orbital and dermal fibroblasts were grown in culture. Confluent monolayers were treated with TGF-beta. PAI-1 in the extracellular matrix was quantitated by radiolabeling the cultures and electrophoresing the cellular material on SDS-PAGE. Medium content was determined by immunoprecipitation of [35S]PAI-1 with a rabbit, anti-human, polyclonal antibody. PAI-1 mRNA was determined by Northern hybridization. RESULTS: TGF-beta increased PAI-1 levels in orbital fibroblasts in a dose-dependent manner, up to 35-fold. The induction was maximal after 16 hours of treatment. The increases in extracellular matrix PAI-1 paralleled those observed in the medium. The steady state levels of the mRNA encoding the protein were upregulated by TGF-beta up to 60-fold 8 hours after the addition of TGF-beta. The fractional increase in PAI-1 expression in orbital fibroblasts was consistently greater than that observed in dermal strains. CONCLUSIONS: Exposure to TGF-beta consistently induces PAI-1 expression in orbital fibroblasts, cells that do not express the polypeptide constitutively at high levels. The effects are mediated at the pretranslational level and involve the upregulation of PAI-1 mRNA. These results suggest that TGF beta may exert a profound regulatory influence on the pericellular proteolytic environment in orbital connective tissue. PMID- 7775120 TI - Modulation of cellular functions in retroorbital fibroblasts using antisense oligonucleotides targeting the c-myc protooncogene. AB - PURPOSE: To examine the signal transduction pathways involved in the activation of orbital fibroblast effector functions relevant to the pathogenesis of Graves' ophthalmopathy (GO). To determine, using antisense technology, whether the c-myc protooncogene is involved in cell proliferation and glycosaminoglycan (GAG) synthesis in cultured orbital fibroblasts (OF). METHODS: The effects of a 16-mer c-myc antisense phosphorothioate oligodeoxynucleotide (S-ODN) on OF monolayers derived from orbital connective tissue of patients with severe GO (n = 6) and healthy individuals (n = 3) were investigated. Quiescent OF monolayers were treated with serum or cytokines and were exposed to increasing concentrations of a c-myc antisense S-ODN and several control S-ODN. Cell proliferation was quantitated by direct cell counting and by immunocytochemistry for the nuclear Ki 67 antigen. Glycosaminoglycan synthesis was examined by [3H] GAG analysis. The effects of the c-myc antisense S-ODN and control S-ODN on c-myc mRNA and protein product levels were analyzed using reverse-transcriptase polymerase chain reaction, immunocytochemistry, and immunoblotting, respectively. RESULTS: Transient suppression of c-myc mRNA and the c-myc protein product by a c-myc antisense S-ODN (2 to 8 microM) strongly inhibited cell proliferation and GAG synthesis in OF derived from patients with GO and healthy individuals. These effects occurred in a dose-dependent manner and were specific for the c-myc antisense S-ODN used. Cell morphology or viability were not affected. CONCLUSIONS: The c-myc protooncogene and its protein product are involved in the proliferative and metabolic activities of OF exposed to serum or cytokines in vitro. C-myc appears to be an essential component of at least two OF cellular activities likely to contribute to the orbital tissue alterations in GO. PMID- 7775121 TI - Cyclosporin protects the eyelid skin from injury after injection of doxorubicin. AB - PURPOSE: The myotoxic drug doxorubicin can treat blepharospasm and hemifacial spasm permanently when injected directly into the eyelid of patients. One side effect of this treatment is the dose-related occurrence of injury to the skin overlying the injection site. The purpose of this study was to determine if injection of the immunosuppressive agent cyclosporin into rabbit eyelids before doxorubicin treatment could reduce the occurrence of injury to the overlying skin and to determine the effect of cyclosporin pretreatment on doxorubicin-induced muscle fiber loss. METHODS: Anesthetized rabbits received injections of varying doses of cyclosporin 20 minutes before injection of either 0.5, 1, or 2 mg doxorubicin. The rabbits were examined daily, and epithelial changes were recorded as to duration, time of onset, and healing. When the skin was completely healed, the animals were killed and eyelid tissue was prepared for morphometric determination of muscle fiber number. Acute inflammation was quantitatively assessed using an Evans blue assay. RESULTS: At specified doses, cyclosporin improved the doxorubicin chemomyectomy protocol in three ways. It delayed the onset of skin injury at the higher doses of doxorubicin, and it markedly decreased the duration of skin injury. At some doses, cyclosporin completely prevented the formation of epithelial defects. The combination, however, did not increase muscle loss compared to doxorubicin alone; in fact, it had a slightly myoprotective effect. A dose range for cyclosporin administration was determined that resulted in a quantitative and dose-dependent reduction in inflammation at the injection site. CONCLUSIONS: The injection of cyclosporin into the eyelids before doxorubicin treatment delayed the onset, reduced the duration, and limited the extent of development of eyelid skin injury. Perhaps by limiting cytokine release, cyclosporin decreased the inflammatory reaction compared to that seen with doxorubicin alone. This combination has the potential to improve patient acceptance of doxorubicin chemomyectomy for the treatment of blepharospasm and hemifacial spasm. PMID- 7775122 TI - Transcranial magnetic stimulation of the posterior parietal cortex degrades accuracy of memory-guided saccades in humans. AB - PURPOSE: Previous neurophysiological studies in the monkey have shown that the posterior parietal cortex (PPC) is involved in the control of memory-guided saccades. In this study, the authors investigated the effect of focal transcranial magnetic stimulation (TMS) over the posterior parietal cortex on accuracy of memory-guided saccades in humans to clarify the cortical region related to controlling memory-guided saccades. METHODS: Single TMS pulses were applied systematically at various locations over the parietal cortex during memory-guided saccades in human subjects. Each subject was instructed to fixate on a central target until the target was extinguished. A lateral target was flashed for 100 msec with unpredictable direction and amplitude. The subject executed a saccade to the remembered position of the previously flashed target in total darkness when the central target was extinguished. Transcranial magnetic stimulation was applied after the extinction of the central target with various latencies. Stimulation sites were identified by three-dimensional magnetic resonance imaging (MRI). RESULTS: Transcranial magnetic stimulation of the right PPC degraded accuracy of rightward and leftward memory-guided saccades in all subjects, when TMS was applied 100 msec after the offset of the central target. On the other hand, TMS of the left PPC showed no effects on accuracy of memory guided saccades. Systematic error of saccade amplitude appeared as a hypometria for rightward saccades. Three-dimensional MRI revealed that the effective stimulation site was located over the posterior portion of the intraparietal sulcus and the superior part of the angular gyrus of the right hemisphere. CONCLUSIONS: These findings strongly suggest that the right PPC is involved in maintaining spatial accuracy of remembered target locations of memory-guided saccades in humans. PMID- 7775123 TI - Renin-containing Muller cells of the retina display endocrine features. AB - PURPOSE: An ocular renin-angiotensin system has been implicated in the proliferation of retinal blood vessels and blindness in diabetes mellitus. Its cellular basis has not been established. The objective was to identify sites of renin synthesis, secretion, and processing in eyes from humans, BALB/c mice, Sprague-Dawley rats, and a hypertensive transgenic rat model (mREN-2) that displays amplified extrarenal renin synthesis. METHODS: Paraffin sections of eyes were incubated with antisera to renin protein, prorenin, vimentin, and Muller cells. Enzyme kinetic renin assay was performed on extracts of whole eyes (excluding lens and vitreous) and comparisons made with adrenal glands and kidneys. For detection of renin mRNA, retinas were separately pooled from BALB/c and Swiss mice. RESULTS: In normal rodent and autopsy human eyes, labeling for renin, vimentin, and Muller cell protein was observed in the cytoplasm of all macroglial Muller cells, with renin labeling most obvious in endfeet closely apposed to retinal blood vessels. Prorenin labeling was not detected. Less intense renin labeling, again without prorenin, was seen in nonpigmented ciliary epithelium of rodents. In transgenic (mREN-2) rat eyes, renin and prorenin labeling of Muller cells and nonpigmented ciliary epithelium were intense. Prorenin was localized to the posterior region of Muller cells but only sparsely to endfeet in rodent retinas, and renin was present only in an active form in amounts one third that of one adrenal. Renin mRNA was readily detected. In human retina, renin was present in active and pro-forms, and the total amount was approximately one fiftieth that of adrenal. CONCLUSION: Renin is synthesized in the retina and is specifically localized to the macroglial Muller cells. Nonpigmented ciliary epithelium also contains renin. The presence of prorenin in the posterior part of the Muller cell, with active renin throughout but notably in endfeet in apposition to retinal capillaries, suggests directional processing of renin. These findings are consistent with earlier suggestions that retinal neovascularization may be associated with Muller cell dysfunction. PMID- 7775124 TI - Differential effects of aqueous and vitreous on fiber differentiation and extracellular matrix accumulation in lens epithelial explants. AB - PURPOSE: Results from this and other laboratories strongly suggest that differences in the properties of the ocular media that bathe cells in the anterior and posterior regions of the lens contribute to its normal growth patterns and polarity. The aim of this study was to compare the effects of aqueous and vitreous on the morphology of lens epithelial explants, with particular attention to changes associated with fiber differentiation. METHODS: Light and electron microscopy were used to assess rat lens epithelial explants cultured with bovine aqueous or vitreous. Immunohistochemistry was used to detect fiber-specific crystallins and extracellular matrix components, and synthesis of extracellular matrix was investigated by autoradiography. RESULTS: Vitreous, but not aqueous, induced morphologic changes characteristic of fiber differentiation, which included cell elongation, organelle loss, and the appearance of ball and socket junctions, as well as the accumulation of beta-crystallin. In addition, vitreous stimulated the synthesis and organization of a distinct basement membrane on explants that resembled the lens capsule, both structurally (regular layers of basal laminae) and immunologically (reactive for laminin and heparan sulphate proteoglycan). CONCLUSIONS: Only one of the ocular media, the posteriorly located vitreous, induced lens epithelial explants to undergo morphologic events characteristic of fiber differentiation. This provides further support for the hypothesis that anteroposterior patterns of cellular responses in the lens are caused by differences in the ocular media. The observation that vitreous also stimulated the synthesis and assembly of capsule-like extracellular matrix suggests that vitreous contains factors that may influence lens capsule formation in situ. PMID- 7775126 TI - Phase II evaluation of the AMAP, 773U82 mesylate, in pancreatic cancer. AB - Pancreatic cancer is the fifth leading cause in cancer related death among adults in the United States. Thirty-thousand new cases of pancreatic cancer are diagnosed each year, most are metastatic at diagnosis and no effective systemic therapy is available. 773U82 mesylate is one of a series of compounds (arylmethylaminopropanediols-AMAPS) which was synthesized at the Wellcome Research Laboratories. AMAPS bind to DNA, show evidence of topoisomerase 2 inhibition and are active in a variety of murine and human preclinical screens. Based on these data a phase II trial of 773U82 mesylate administered at 800 mg/m2 daily x 3 at a 4 h infusion repeated every three weeks was carried out. Patients eligible for these trials had histologic proof of adenocarcinoma, good performance status, and normal organ function. This was a multi-institutional trial. Nineteen patients were entered; 15 patients were fully eligible and 4 were ineligible, but were evaluated. Thirteen patients were fully evaluable for response and no response was seen. Median time to progressive disease among eligible patients was 56 days. Toxicity of 773U82 mesylate was myelosuppression which was not prohibitive. 773U82 mesylate is not active in pancreatic cancer. PMID- 7775125 TI - Intracameral injection of antigen potentiates the production of antigen-specific T cell proteins in serum after the induction of delayed-type hypersensitivity. AB - PURPOSE: To determine whether the introduction of antigen into the anterior chamber induces the production of extracellular antigen-specific T cell proteins (T cell antigen-binding molecules [TABM] specific for the antigen. METHODS: Balb/c mice received an intracameral or subconjunctival injection of trinitrophenylated spleen cells (TNP spleen cells) before skin sensitization and challenge with picrychloride. The production of TNP-specific TABM in serum was quantified by enzyme-linked immunosorbent assay-based antigen binding and immunoblotting using a rabbit antiserum raised against a monoclonal antigen specific T cell protein that induces suppressor T cells. RESULTS: Intracameral, but not subconjunctival, injection of TNP spleen cells before contact sensitization increased the level of TNP-specific TABM in serum. At 2 days, TABM levels began to rise and peaked at 5 days after contact sensitization. Anterior chamber injection of TNP spleen cells alone into nonimmunized mice did not induce a detectable increase of TNP-specific TABM in serum. Mice that did not receive an intracameral TNP spleen cell injection but were made contact sensitive to TNP showed a diminished TNP-specific TABM response. Specificity of the TABM induced by intracameral-injection and sensitization for the TNP hapten was documented by showing that the induced TABM binds TNP-bovine serum antigen (BSA) but does not bind either BSA alone or azobenzenearsonate-ovalbumin and that immune sera raised against ovalbumin did not contain an increase in TNP-specific TABM. TNP-specific TABM in the sera of mice receiving an intracameral injection of TNP spleen cells, followed by contact sensitization with picrylchloride (PCl), were purified by affinity for TNP and were resolved by polyacrylamide gel electrophoresis and immunoblotting as M(r) 110,000 polypeptides. CONCLUSIONS: Serum levels of TNP specific TABM induced by contact sensitization alone are enhanced fourfold to fivefold when sensitization is preceded by the intracameral, but not the subconjunctival, injection of TNP spleen cells. The authors propose that besides suppression of systemic delayed type hypersensitivity, the intracameral injection of antigen into nonimmune mice may prime an increased production of TABM, which may indicate systemic activation of the immunoregulatory T cell circuit. PMID- 7775127 TI - Phase I study of mitonafide with a 3-day administration schedule: early interruption due to severe central nervous system toxicity. AB - Eleven patients with solid tumors for whom effective therapy was not available entered a phase I study of mitonafide given as a short intravenous (i.v.) infusion daily for 3 consecutive days. The initial dose level was selected according to the experience from another phase I study using a 5-day administration schedule. Six patients entered the first dose level (180 mg/m2/day x 3 days) and 4 of them had grade 3-4 leukopenia. This level was considered to be the maximum tolerated dose (MTD) and no further dose escalations were attempted. The following 5 patients received a dose approximately 10% inferior to the previous one (160 mg/m2/day x 3 days). Three of them had grade 3-4 neutropenia. Three partial responses were observed in total. After inclusion of 11 patients, an unexpected toxicity, central nervous system (CNS) toxicity, consisting of severe loss of memory, temporospatial disorientation and high integrative function impairment was observed in 5 patients (46%). A median patients' follow up of 3 months after treatment discontinuation showed that these alterations were progressive and not reversible. This disabling toxicity prompted us to an early study interruption. In conclusion, mitonafide, when administered as a short 3-day i.v. infusion, can induce severe and irreversible CNS toxicity. Nevertheless, since antitumor activity has been observed, further development of the drug is recommended with different schedules of administration that have shown not to produce neurotoxicity, i.e., 5-day continuous infusion. PMID- 7775128 TI - Phase I/II trial of dipyridamole, 5-fluorouracil, leukovorin, and mitoxantrone in metastatic breast cancer. AB - Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m2 by mouth every 6 h (700 mg/m2/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m2 was given intravenously immediately prior to 5-FU 375 mg/m2 intravenously on days 1-5. Mitoxantrone 6 mg/m2 was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1 2, 5-FU 375 mg/m2 days 1-2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0-3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer. PMID- 7775130 TI - High-dose aminothiadiazole in advanced colorectal cancer. An Illinois Cancer Center phase II trial. AB - Thirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five percent of patients had grade 3 or 4 toxicity. There were no responses in 27 evaluable patients. Median survival was 12 months. Aminothiadiazole, at higher doses than used in previous reports, when given with NSAID's, had no significant activity against large bowel cancer. PMID- 7775129 TI - Postincubation with aclarubicin reverses topoisomerase II mediated DNA cleavage, strand breaks, and cytotoxicity induced by VP-16. AB - In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed strand break formation was prevented in a small cell lung cancer (SCLC) cell line, when the cells were incubated with aclarubicin prior to treatment with VP-16. In the present work, we studied the effect of adding aclarubicin to the cell suspension after VP-16. In a clonogenic assay, we found that the cytotoxicity induced by VP-16 in SCLC cells was inhibited when cells were postincubated with aclarubicin. The addition of aclarubicin at any time in relation to VP-16 was able to stop further cytotoxicity induced by the topoisomerase II (topo-II) targeting drug. Aclarubicin was also found to antagonize the cytotoxicity induced by VM-26 (teniposide), and m-AMSA. With the alkaline elution technique we found that postincubating the cells with aclarubicin inhibited VP-16-induced DNA strand break formation. In an in vitro system with purified topo-II and naked DNA we likewise found, that postincubation with aclarubicin prevented VP-16 induced cleavage. In the same in vitro system, also baseline cleavage induced by topo-II was inhibited when aclarubicin was present. Importantly, aclarubicin exerted the antagonism to topo-II targeting drugs both when administered prior to and after the topo-II targeting agents. Thus, our data suggest that sequential rather than simultaneous administration of aclarubicin and topo-II targeting agents may be superior with respect to net cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775131 TI - Pharmaceutical development of a parenteral formulation of the novel anti-tumor agent carzelesin (U-80,244). AB - The aim of this study was to design a parenteral dosage form for the investigational cytotoxic drug carzelesin. A stable formulation in PET (Polyethylene glycol 400/absolute ethanol/Tween 80, 6:3:1, v/v/v) was developed. The prototype, containing 0.50 mg carzelesin in 2.0 ml PET formulation, was found to be the optimal formulation in terms of solubility, stability and dosage requirements in phase I clinical trials. Quality control of the formulation showed that the pharmaceutical preparation of carzelesin in PET is not negatively influenced by the manufacturing process. Shelf life studies demonstrated that the formulation is stable for at least 1 year, when stored at -30 degrees C in the dark. In addition, the stability of carzelesin in the PET formulation is discussed as a function of temperature, additives and after dilution in infusion fluids. PMID- 7775132 TI - Phase II study of elsamitrucin in non-small cell lung cancer. AB - Elsamitrucin (BMY-28090) a novel fermentation product has demonstrated pre clinical anti-tumour activity against a number of cell lines. The dose limiting toxicity in phase I studies was a reversible increase in hepatic transaminase. This study was initiated to determine the activity of elsamitrucin in patients with previously untreated, bi-dimensionally measurable, cytologically or histologically proven, non-small cell lung cancer who were not curable by surgery. Elsamitrucin at a dose of 25 mg/m2 was administered intravenously over 5 10 min weekly for a minimum of 6 weeks. Seventeen patients were entered on study, 15 were evaluable for toxicity and 14 evaluable for response. No responses were documented in the 14 patients evaluable for response. Both hematological and non hematological toxicities were mild to moderate in severity. The commonest being nausea, vomiting, lethargy and local skin reactions at the site of the infusion. These results indicate that elsamitrucin when given in this dose and schedule to patients with surgically incurable non-small cell lung cancer has no activity. PMID- 7775133 TI - Phase II trial of PALA and 6-methylmercaptopurine riboside (MMPR) in combination with 5-fluorouracil in advanced pancreatic cancer. AB - The biochemical modulators PALA, an inhibitor of aspartate transcarbamylase which depletes uridine nucleotide pools, and 6-methylmercaptopurine riboside (MMPR) which inhibits purine metabolism, selectively potentiate the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Based on a phase I trial of this combination, we performed a phase II trial in patients with advanced pancreatic cancer. PALA 250 mg/m2 was administered i.v. on day 1, followed 24h later by MMPR 150 mg/m2 as a bolus i.v. injection, and 5-FU 2300 mg/m2 by 24h infusion. Treatments were repeated weekly. Seventeen patients, all previously untreated with chemotherapy, were entered, of whom 14 are evaluable for response. Toxicity > or = grade 2 included nausea (6/17), vomiting (4/17), diarrhea (3/17), stomatitis (5/17), and neurotoxicity (2/17). Among 14 evaluable patients there were no partial responses, and two patients with stable disease. Pretreatment with PALA and MMPR is insufficient to enhance the activity of 5-FU in pancreatic cancer. PMID- 7775134 TI - Phase II trial of liposomal encapsulated doxorubicin in patients with advanced renal cell carcinoma. AB - Fourteen patients with advanced renal cell carcinoma were treated on a phase II trial with liposomal encapsulated doxorubicin (Lipodox, LED). None of the fourteen evaluable patients achieved a complete or partial response. Myelosuppression was the most common toxicity and no cardiac toxicity was evident. Seventy-nine percent (11 of 14) of patients experienced grade III or IV neutropenia. In summary, LED did not show antitumor activity in the treatment of advanced renal cell carcinoma. PMID- 7775135 TI - Phase II study of carboplatin and edatrexate (10-EdAM) with leucovorin rescue for patients with recurrent squamous cell carcinoma of the head and neck. AB - Recurrent squamous cell carcinoma of the head and neck is poorly responsive to chemotherapy in most patients; therefore, the development of new approaches is essential. Edatrexate is a new antifolate with improved preclinical antitumor activity when compared to methotrexate. The purpose of this study was to define the feasibility and efficacy of combining edatrexate with another active single agent, carboplatin in chemotherapy-naive recurrent disease. Carboplatin was given as an outpatient on day 1 at a dosage based on the formula: Dose (mg/m2) = (0.091) (creatinine clearance) (body surface area) (desired percentage change in platelet count) + 86. Edatrexate (80 mg/m2) was given on days 1, 8, and 15 of a 21 day cycle. Calcium leucovorin 15 mg was given orally every 6 h for 4 doses after edatrexate. Of the 26 patients entered on the study, 1 was invaluable for toxicity or response and 3 patients were evaluable for toxicity only. Grade 3 or 4 neutropenia occurred in 2 patients each, and grade 3 or 4 thrombocytopenia occurred in 2 and 4 patients, respectively. Grade 3 stomatitis occurred in only two patients. Overall, major responses occurred in 2 of 22 evaluable patients (9%). The combination of carboplatin and edatrexate was not superior to the results expected with either agent alone. PMID- 7775136 TI - Phase II trial of piroxantrone in metastatic breast cancer. A Southwest Oncology Group study. AB - Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m2 intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m2. We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer. PMID- 7775137 TI - Hepatoma/merbarone. A Southwest Oncology Group study. AB - Sixteen eligible patients with hepatocellular carcinoma, previously untreated, received merbarone 1000 mg/m2/d for five consecutive days every 21 days. No complete or partial response to treatment was obtained. Seven patients had grade 4 granulocytopenia. One patient died with renal failure. Merbarone in this dose and schedule was ineffective in the treatment of hepatocellular carcinoma. PMID- 7775138 TI - Phase II study of edatrexate in advanced head and neck cancer. A Southwest Oncology Group study. AB - Fifty-two patients with persistent, recurrent and/or metastatic squamous cell cancer of the head and neck were treated with weekly edatrexate, 80 mg/m2. Nine patients had received previous adjuvant or neoadjuvant chemotherapy. Of the 46 eligible patients, two complete responses and one partial response were observed (6%, 95% confidence interval of 1-18%). The most common toxicities were myelosuppression and mucositis, but dermatologic toxicity was also observed in 25% of patients. Edatrexate appears to have limited activity in advanced head and neck cancer. PMID- 7775139 TI - Phase II trial of 6-thioguanine in advanced renal cell carcinoma. An Illinois Cancer Center study. PMID- 7775140 TI - Anxiety disorders. PMID- 7775141 TI - Depression in adolescence. PMID- 7775142 TI - Chronic depression. PMID- 7775144 TI - Advances in understanding obsessive compulsive disorder. PMID- 7775143 TI - ACE inhibitors in the management and prevention of heart failure. PMID- 7775145 TI - Occupational disorders of the upper limb. PMID- 7775146 TI - Referrals to Irish accident and emergency departments. AB - A prospective survey of samples of thirty consecutive referrals from general practitioners in fifteen European Countries (the European study of Referrals from Primary Care), found that Irish doctors sent a higher proportion (20.6%) of referrals to Accident and Emergency (A&E) Departments than in any other country in the study. Further analysis of the Irish sample showed that 57% of these patients were referred to specialists other than Emergency and Trauma (E&T) (i.e. 12.7% of all referrals). These referrals were mostly for acute medical or surgical conditions requiring inpatient treatment. More non-E&T referrals were sent by doctors closer than 10 km from hospital (26.8% of all their referrals), as compared with doctors 10 km or further from hospital (8.1% of all their referrals). Doctors older than 40 years sent more non-E&T referrals to A&E Departments (16.9% of all their referrals) as compared with those aged 40 years or younger (9.6% of all their referrals). In contrast, referrals to Emergency and Trauma specialists were associated with greater distance to hospital, as doctors closer than 10 km from hospital made only 1.6% of all referrals to the E&T specialty, while doctors 10 km or further from hospital made 12.5% of all referrals to E&T specialists. The author recommends that referrals to non-trauma specialists in the Republic of Ireland should go directly to these specialists, as in all other countries in Europe, thus freeing Emergency and Trauma specialists for their proper Accident and Emergency function. PMID- 7775147 TI - A comparison of attendance for drug misuse to Dublin accident & emergency departments 1985-1993. AB - We compared attendance by Drug Misusers to the Accident & Emergency Departments (A&E) in the greater Dublin area during September 1985 and April 1993. The study took the form of a questionnaire administered by the previously trained A&E staff to attenders who were currently (within the past six months): experimenting with drugs, abusing drugs or drug dependent. Seventy three drug misusers were identified in September 1985 and 68 in April 1993. Poly substance misuse was a major feature of the 1993 survey and Benzodiazepines replaced Heroin as the major drug of misuse. There was a significant increase in the misuse of prescribed opiates, in particular morphine sulphate, methadone and DF118. Physical problems associated with drug misuse were more common in 1993 because of the new trend of crushing and injecting the morphine sulphate tablet. Patients continue to inject drugs and are poor attenders at needle exchange programmes. We feel that all doctors should exercise caution in their prescribing habits in view of the alarming increase in the misuse of prescribed medication as indicated by our figures. PMID- 7775148 TI - Nonmelanoma skin cancer in an Irish population: an appraisal of risk factors. AB - Previous Irish studies have shown a high prevalence of nonmelanoma skin cancer (NMSC). However, unlike elsewhere where the generally quoted ratio of basal cell carcinoma (BCC):squamous cell carcinoma (SCC) is at least 4:1 the ratio in Ireland was found to be 1:1. We examined this ratio in patients attending the dermatology outpatients and determined risk factors for the development of NMSC within an Irish population where 75% of the population have been shown to have skin type 1 or 11. The study consisted of a retrospective 10 year review of biopsy proven cases of NMSC and a prospective case control study of NMSC which allowed examination of risk factors and comparison to a control group. The BCC:SCC ratio in the retrospective study was 3:1. In the prospective study the ratio of BCC:SCC was 4.4:1. Skin type 1 and numerous freckles were identified as risk factors in the NMSC group. PMID- 7775150 TI - Sneddon's syndrome--clinical course and out-come. AB - Five patients presented with Sneddon's syndrome characterised by cerebral infarction, livedo reticularis, hypertension, epilepsy and a progressive dementia. Two patients had raised anticardiolipin antibody titres. The clinical symptoms and immunological disturbance in Sneddon's syndrome and the antiphospholipid syndrome are similar, and may indicate the importance of immune mediated thrombosis in Sneddon's syndrome. PMID- 7775149 TI - Clinicopathologic observations in 100 consecutive patients with fatal head injury admitted to a neurosurgical unit. AB - A neuropathologic study of 100 patients with fatal head injuries admitted to a neurosurgical unit revealed hypoxic-ischaemic brain damage in 74% and diffuse axonal injury in 42% of patients respectively. Of the seven patients who died as a result of extracerebral injuries, there were four in whom death due to hypovolaemic shock, was considered potentially avoidable. This study indicates that there is scope for improvement in the management of patients with acute head injury, particularly in the prevention of secondary brain damage, and in the need to increase awareness of potentially life threatening extracerebral injuries as a cause of coma. PMID- 7775151 TI - Recurrent ovarian carcinoma: diagnosis and second-line therapy. AB - Approximately 10% of patients with ovarian cancer will develop a recurrence. Successful treatment of recurring disease has been documented, and recent developments in chemotherapy are encouraging. In our study, CA125 Tumour Marker was a useful marker to monitor the course of such disease, and detected recurring ovarian cancer at a sub-clinical level, leading to earlier diagnosis. This may have implications for outcome. PMID- 7775152 TI - A comparison of parenteral tenoxicam and diclofenac in the treatment of acute soft tissue injury of the lower limb. PMID- 7775153 TI - Psoriatic arthropathy. PMID- 7775154 TI - Alterations in the pulmonary and systemic immune response in rats exposed to coal fly ash. AB - The effect of intratracheally injected fly ash on the development of pulmonary and systemic immunity was studied in rats. Following intratracheal and intraperitoneal immunisation with sheep red blood cells (SRBC) there was an appearance of antibody forming cells (AFC) in lung associated lymph nodes (LALN) of animals exposed to either fly ash or physiological saline. Enumeration of AFC in LALN after immunisation by either of the routes, revealed a reduction in the number of AFC in LALN of fly ash exposed rats in comparison to saline exposed animals. The reduction in the number of AFC was more pronounced after exposure of Cd-coated fly ash. The AFC appeared in the spleen only after immunisation through intraperitoneal route and the number of AFC in spleen of the fly ash and saline exposed group of animals did not show any significant difference. These results demonstrate that fly ash burden of lungs results in an impairment of the local immune response of the lungs without an associated effect on the systemic immunity. PMID- 7775155 TI - Effects of an S-adenosyl-L-homocysteine hydrolase inhibitor on murine macrophage activation and function. AB - The S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor MDL 28,842 has been demonstrated to be a potent inhibitor of T-cell activation, both in vitro and in vivo. Although the inhibition of T cells in vitro was independent of macrophages, the direct effect of MDL 28,842 on macrophages is unknown. In this report the effects of MDL 28,842 on macrophage cytokine production, cell-surface antigen expression, and antigen processing and presentation were examined. Lipopolysaccharide (LPS) stimulation of IL-1 synthesis by peritoneal macrophages was not effected by MDL 28,842 using cells obtained from B10.A and B10.B mice and weakly inhibited using cells from BALB/C mice (IC50 > 10 microM). In contrast, TNF-alpha synthesis by BALB/C macrophages was inhibited by MDL 28,842 with an IC50 < 0.1 microM. B10.A and B10.B macrophages did not produce detectable TNF alpha in response to LPS in this system. Treatment with 1-10 microM MDL 28,842 resulted in a modest decrease in major histocompatibility complex class II (MHC II) determinant expression by Interferon-gamma-activated macrophages. The expression of other cell-surface markers was not altered in the presence of MDL 28,842. The processing of antigen and its presentation by MHC class-II-positive macrophages to a T-cell hybridoma was also not affected by incubation with MDL 28,842.) PMID- 7775157 TI - Development of a binding assay for the B1 receptors for kinins. AB - A novel binding assay to kinin B1 receptors was developed, based on the design of a high-affinity agonist ligand, [125I]Tyr-Gly-Lys-Aca-Lys-des-Arg9-BK. Binding to rabbit aortic smooth muscle cells is highly temperature-dependent (optimal at 37 degrees C); apparent binding equilibrium is reached within 30 min, and competition by kinin analogs reveals the expected correlation with the B1 receptor pharmacology. The dissociation constant (Kd) of the labeled ligand is approx. 0.2 nM and this value does not change significantly as a function of cytokine pretreatment. However, the receptor abundance (Bmax) is significantly increased (1.5-fold) by pretreating the cells with interleukin-1 (IL-1), while oncostatin M (OSM) produces a marginal increase of the Bmax. This assay may be useful in documenting the regulation of B1 receptors in pathology. PMID- 7775156 TI - Pretreatment with beta-funaltrexamine blocks morphine-mediated suppression of CTL activity in alloimmunized mice. AB - The effect of prolonged exposure to morphine on cytotoxic T lymphocytes (CTL) and splenic natural killer (NK) activity was investigated. Daily administration of morphine (50.0 mg/kg, s.c.) to alloimmunized mice for 11 days resulted in a significant decrease (25-50%) in peritoneal and splenic CTL activity but not splenic NK activity. To identify the effector cell population mediating cytolysis, cell enrichment studies were carried out. The results of these studies indicated the CTLs are CD8+ CD4-. Chronic morphine treatment increased the percentage (25-30%) of CD3+ CD4+ and CD8+, but not Ig+ cells in the spleen relative to saline-treated controls. Pretreatment of mice with the mu-selective antagonist, beta-funaltrexamine blocked morphine-mediated suppression of splenic and peritoneal CTL activity as well as the increase in CD3+ CD4+ and CD8+ splenic lymphocytes. These results indicate the generation of CTLs in vivo is sensitive to chronic morphine exposure implicating opiates as important co-factors through modulation of cell-mediated immunity. PMID- 7775158 TI - Cell surface expression of heat shock proteins in dog neutrophils induced by mitochondrial benzodiazepine receptor ligands. AB - The effect of peripheral-type benzodiazepines on dog neutrophil stimulation was studied. Ro 5-4864 (a specific ligand of mitochondrial benzodiazepine receptor) and diazepam (which binds both to mitochondrial and central benzodiazepine receptors) did not show any direct toxic effect against neutrophils. PK 11195, a putative antagonist of the mitochondrial benzodiazepine receptor and an isoquinoline derivative, had a direct toxic effect at a concentration of 5 x 10( 5) M (72% of cells were viable). Ro 5-4864 (10(-6)-10(-4) M) and diazepam (10(-6) 2.5 x 10(-4) M) induced an intracellular oxidative stress in dog neutrophils. These compounds, in a micromolar range, also induced a concentration-dependent cell surface expression of heat shock protein (HSP) families. The percentages of positive cells that express these proteins were: 76.2% for HSP 27 kDa; 54.3% for HSP 72 kDa and 69.6% for HSP 90 kDa for Ro 5-4864 (10(-4) M), and 66.7% for HSP 27 kDa; 45.4% for HSP 72 kDa and 78.3 for HSP 90 kDa for diazepam (2.5 x 10(-4) M). It appears that this HSP expression, induced by peripheral-type benzodiazepines could be mediated by an intracellular oxidative stress. PMID- 7775160 TI - Morphine inhibits the development of allogeneic immune responses in mouse lymph node. AB - Morphine and related opiates are often administered to relieve post-operative and chronic pain following transplantation surgery. Opiates have been shown to suppress a variety of immune parameters in both animal models and man. In the present study, we investigated whether morphine affects allogeneic immune responses by injecting C57BL/6 mice in the footpad with allogeneic spleen cells and examining changes in the draining popliteal lymph node (PLN). Morphine (administered as subcutaneous implants) had profound inhibitory effects on the development of alloreactivity manifested as a suppression of: (1) lymph node hyperplasia, (2) mixed lymphocyte reactivity (MLR) in PLN cells and (3) the number of CD4+ and Thy 1.2 lymphoid subsets. These inhibitory effects of morphine were abolished or dramatically reduced by co-administration of the opiate antagonist, naltrexone, indicating that suppression of allo-sensitization was opiate receptor mediated. In toto, these findings demonstrate that morphine administration interferes with the development of allogeneic immune response in mouse lymph node through an opiate receptor mediated mechanism. PMID- 7775159 TI - Involvement of histamine or tumor necrosis factor in early-type hypersensitivity. AB - A novel early-type hypersensitivity (ETH) reaction, manifested as capillary congestion, increase of vasopermeability, and plasma protein leakage, can be induced within 1 h after challenge of antigen-sensitized mice. The mediators involved in ETH varied among different strains of mice. The poly(Glu60Ala30Tyr10) (GAT)-induced ETH in BALB/c mice was blocked by diphenhydramine (histamine H1 antagonist) and ketanserine (serotonin antagonist), but not by cimetidine (histamine H2 antagonist). These results indicate that both histamine and serotonin are involved, and that the histamine effect is mediated through a H1 receptor. Meanwhile, GAT-induced ETH in B6 mice was inhibited by anti-TNF alpha antibody suggesting that TNF alpha is involved. The mice can be classified into either histamine or TNF alpha type based on the pattern of mediator involved in ETH. A/J and CBA strains as well as BALB/c mice were classified as histamine type while A. TL, B10.BR, and C3H/He in addition to B6 mice were TNF alpha type. The observation that GAT-induced ETH in (BALB/c x B6)F1 mice was inhibited by both diphenhydramine and anti-TNF alpha suggests that the mediation of the actions of histamine or TNF alpha by GAT was genetically controlled and inherited as the dominant trait in (BALB/c x B6)F1 mice. ETH could be passively transferred by heat (56 degrees C, 4 h)-treated anti-GAT sera. Sera derived from the histamine type transferred ETH across the type barrier and histamine was the mediator, irrespective of the type of the recipient. However, sera derived from TNF alpha type only transferred ETH to the mice of the same TNF alpha type and TNF alpha was the mediator. PMID- 7775161 TI - Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type cytokine production. AB - Corticosteroids (CS) are very potent immunosuppressive agents and are widely used to treat inflammatory diseases. On the basis of their clinical efficacy and potency CS have been divided into different classes. In the present study we investigated whether the class-associated effects of CS are correlated with a differential in vitro effect on cytokine production by T lymphocytes. Therefore, we determined the in vitro effects of CS on the production of Th1- and Th2-type cytokines. The addition of CS, in the range of 10(-9) to 10(-4) M, resulted in a class- and dose-dependent inhibition of the production of both IFN-gamma and IL 4. Notably, at the lowest doses tested, hydrocortisone and hydrocortisone 17 butyrate had a stimulatory effect on IL-4 production. CS class-dependently inhibited the IL-2 production by T cells but did not affect IL-2R expression of the T cells. Addition of rIL-2 could not completely restore the inhibitory effect of the CS on proliferation and on IFN-gamma and IL-4 production, indicating that CS act only partially via inhibition of IL-2 production. The demonstrated positive correlation between the clinical efficacy and the in vitro effects of the different classes of CS strongly suggests that the effect of CS on T-cell mediated inflammation follows from inhibition of proliferation and cytokine production by T lymphocytes. The in vitro method used will be valuable for investigating and classifying new types of CS and other substances for applications in T-cell-mediated diseases. PMID- 7775162 TI - Development of the Nurse Information System (NIS): an update on progress. PMID- 7775163 TI - Progress report: nurse aide job analysis study. PMID- 7775164 TI - Writing CST default responses for pediatric and obstetrical nursing activity terms. PMID- 7775165 TI - External funding obtained to study the effectiveness of nurse disciplinary actions. PMID- 7775166 TI - Job analysis study of entry-level licensed practical/vocational nurses. PMID- 7775167 TI - National Council initiates study comparing the effectiveness of two approaches to the regulatory management of chemically impaired nurses. PMID- 7775169 TI - Computerized Clinical Simulation Testing (CST) update. PMID- 7775168 TI - Promoter Member Board participation in the Nurse Information System. PMID- 7775171 TI - Constructing the CST default client response database. PMID- 7775170 TI - Creating database links between nursing diagnoses and nursing activities. PMID- 7775172 TI - Efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine. Dihydroergotamine Nasal Spray Multicenter Investigators. AB - Recently, a new nasal spray formulation of dihydroergotamine was developed which facilitates at-home treatment of migraine. We studied the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the acute treatment of classic and common migraine in two, identical, double-blind, randomized, placebo-controlled trials. Of the 229 patients enrolled, 206 (102 dihydroergotamine nasal spray, 104 placebo) were included in the intent-to-treat analyses; 182 treated two headaches and 24 treated one headache. Based on both the patients' and physicians' ratings, dihydroergotamine nasal spray was significantly superior to placebo for reducing the severity of headache pain in both studies, and in relieving nausea in Study 2. The onset of significant efficacy with dihydroergotamine nasal spray compared to that with placebo for both severity of headache pain and relief of nausea occurred at 1 hour in Study 2 and at 3 hours in Study 1. Dihydroergotamine nasal spray was also significantly superior to placebo for the relief of headache pain in both studies. Based on the physicians' global evaluations of treatment efficacy for headache pain, 71% of the dihydroergotamine-treated patients in Study 2 and 59% of their counterparts in Study 1 were considered to be responders. The dihydroergotamine-treated patients had less newly-occurring vomiting than the placebo-treated patients. The majority of adverse events reported by the dihydroergotamine-treated patients were nasopharyngeal. The results demonstrate the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine attacks. PMID- 7775173 TI - Sinus headaches reconsidered: referred cephalgia of rhinologic origin masquerading as refractory primary headaches. AB - Headache associated with acute sinusitis is a well-recognized entity; the diagnosis is easily made due to the associated nasal and sinus symptoms. However, the phenomenon of referred headache from chronic sinusitis or intranasal abnormalities or both without upper respiratory symptoms is not well understood. Only recently have the nasal and sinus cavities been adequately visualized by both the human eye and radiographic techniques; a fact that may account for the historic neglect in considering this region a factor in headache etiology. Modern techniques employed in the workup of sinusitis, namely the use of rigid nasal endoscopes and coronal-plane CT scanning, have greatly enhanced the clinician's ability to evaluate and diagnose pathology in this area. This report describes a series of patients presenting with various primary headache syndromes without significant nasal or sinus symptoms who failed to respond to conventional antiheadache therapy. On nasal endoscopic and coronal CT examinations, various intranasal and sinus abnormalities were found (either anatomic variations or subclinical inflammation). Medical and/or surgical therapy addressing the sinonasal pathology resulted in improvement in every case, ranging from decreased severity of attacks to total resolution of headaches. A model explaining the possible mechanism of referred vascular-type headache from sinus and nasal origin is proposed. PMID- 7775174 TI - Long-term results of radiofrequency rhizotomy in the treatment of cluster headache. AB - Although the primary treatment of chronic cluster headache is medical, surgical treatment is sometimes used. The authors reviewed the charts of seven patients (ages 36 to 68 years) with chronic cluster headache to identify who responded best to percutaneous stereotactic radiofrequency rhizotomy after medical treatment failed. All patients had immediate pain relief after surgery. At follow up (median 5 years, range 2 to 20 years), two patients remained pain-free 7 and 20 years later (excellent results); three patients had mild pain recurrence that was well controlled on medications (good results) 6 to 12 months after surgery; and two patients had major pain recurrence 4 days and 2 months after surgery (poor results). Six patients had relief of vasomotor symptoms. One patient had transient diplopia and keratitis without permanent sequelae. Both patients with excellent results had preoperative major pain around the eye; both patients with poor results had major pain around the temple, ear, and cheek; and the three patients with good results had pain equally severe in the eye, temple, and cheek. There was no association between patient age or sex, pain duration, preoperative response to lidocaine blockade, or previous surgery with pain relief. No differences occurred in pain relief between patients with dense hypalgesia and patients with analgesia. The authors conclude that (1) some patients with chronic cluster headache treated by percutaneous stereotactic radiofrequency rhizotomy achieve long-term pain relief, and (2) surgery on the trigeminovascular system alone may not cure the condition in patients with major pain around the temple, ear, and cheek. PMID- 7775175 TI - A preliminary report on hyperbaric oxygen in the relief of migraine headache. AB - Oxygen inhalation was early advocated as a treatment for migraine headache. It has been theorized that the efficacy of raising blood oxygen levels in vascular headache is mediated by vasoconstriction and metabolic effects. Hyperbaric oxygen can provide a much greater level of blood oxygenation than can provide a much greater level of blood oxygenation than normobaric oxygen, and in recent studies it has been used in the treatment of cluster headache. The purpose of this study was to compare the effects of hyperbaric oxygen and normobaric oxygen in migraine. Twenty migraineurs were divided randomly into two groups and studied in a hyperbaric chamber during a typical headache attack. Global headache severity was measured by a verbal descriptor scale before and after exposure to oxygen. One group received 100% oxygen at 1 atmosphere of pressure (normobaric) while the other received 100% oxygen at 2 atmospheres of pressure (hyperbaric). One of the 10 patients in the normobaric group achieved significant relief of headache symptoms, while 9 of 10 in the hyperbaric group found relief. Based on a chi square test, this difference is significant at the P < .005 level. Those patients who did not find significant relief from normobaric oxygen were given hyperbaric oxygen as above. All nine found significant relief. The results suggest that hyperbaric (but not normobaric) oxygen may be useful in the abortive management of migraine headache. Possibilities for the mechanism of this effect, in addition to vasoconstriction, include an increase in the rate of energy-producing and neurotransmitter-related metabolic reactions in the brain which require molecular oxygen. PMID- 7775176 TI - The impact of migraine on health status. AB - PROBLEMS: What is the effect of migraine on health status, defined as the patient's physical, psychological, and social functioning? And, suppose that the health status of migraine sufferers appears to be impaired, to what extent is this a consequence of migraine-associated comorbidity rather than of migraine itself? METHODS: A group of 846 migraineurs, selected from the general population following IHS criteria, and a control group were surveyed with the Medical Outcomes Study 36-item Short-Form Health Survey, Nottingham Health Profile, EuroQol instrument, and the COOP/WONCA charts. Questions on demographic characteristics and comorbidity were included. RESULTS: The health status of migraineurs appeared to be significantly impaired in comparison to the control group. Because statistical significance is distinct from relevance, effect size estimators were employed. Although the direction of the differences indicated consistently a worse health status of the migraineurs, regardless of the instrument used, the sizes of the differences were small to medium. Self-reported comorbidity, especially depression, was more prevalent in the migraine group. However, this offered only a partial explanation for the impaired health status of the migraine group. CONCLUSIONS: Migraine has an independent moderately deteriorating effect on the daily functioning of individuals. PMID- 7775177 TI - Is abdominal pain a feature of adult migraine? AB - Recurrent abdominal pain in children, frequently diagnosed as "abdominal migraine," is thought to evolve into more typical migraine headache during the teens and twenties. If this transformation occurred, we would expect some adult migraineurs to retain abdominal pain; but we could not recall this symptom being mentioned by patients. However, without direct questioning the absence cannot be assumed. We, therefore, asked 100 migraineurs about abdominal symptoms during migraine attacks: only one experienced unexplained abdominal pain. We conclude that abdominal pain is not a feature in adult migraineurs, leading us to support the notions that: (1) recurrent abdominal pain of childhood has a number of causes; (2) abdominal migraine may be an incorrect attribution and is liable to be over diagnosed; (3) abdominal migraine requires more precise definition; (4) the transition from childhood abdominal migraine to adult migraine needs precise prospective study. PMID- 7775178 TI - The event-related potential P300 during headache-free period and spontaneous attack in adult headache sufferers. AB - The event-related potential P300 has been studied in 15 migraine without aura sufferers, and in 15 episodic tension-type headache sufferers, during pain-free periods and during spontaneous headache attacks. There were no variations of potential, either of P3 latency or N2-P3 amplitude, in either group during the interictal period. Similarly, there were no variations of the P300 parameters in the group of tension-type headache subjects during headache attacks; by contrast, a significant elongation of latency (P < 0.01) and an increment of N2-P3 wave amplitude (P < 0.002) was observed in the group of migraineurs. The authors discuss the data in accordance with the etiopathogenic theories of migraine and the hypothesis that acetylcholine and norepinephrine are the neurotransmitter able to affect the event-related potential P300, which reflects cerebral activity during sensory information processing and analysis. PMID- 7775180 TI - Toward a standard drug formulary for the treatment of headache. AB - The recent publication of drug formularies by third-party payers has serious implications for the practice of medicine. These formularies list the medications for which the consumer can be reimbursed by the third-party payer. The most restrictive of the five formularies I have received lists only two agents for the treatment of migraine headaches: Cafergot (at an incorrect dose of 1/100 mg) and Ergotrate which is no longer available. The most liberal of the formularies lists analgesics, Cafergot, Midrin, and Imitrex for the treatment of acute attacks, and as prophylactic agents, Inderal, Sansert, and analgesics (known to cause rebound headaches when used in this fashion in migraine patients). Abortive agents of proven value, such as DHE-45 and NSAIDs, and preventative medications, such as calcium channel blockers, tricyclic antidepressants, serotonin reuptake inhibitors, methylergonovine, and divalproex sodium, are not available. No one could quarrel with a goal of developing a cost-effective formulary. However, the authors of these formularies have clearly demonstrated their inability to provide even a current, accurate, and adequate formulary by existent standards of care in the treatment of migraine headache. While it is easy to criticize these formularies, it is more difficult to develop a comprehensive list that would satisfy the practitioners' need to provide relief for their patients with a minimum of side effects, and the needs of third-party payers (presumed) to provide quality care at the most economical level. PMID- 7775179 TI - Dopamine hypersensitivity in migraine: role in apomorphine syncope. AB - There is some evidence supporting a potential role of hypersensitivity of the dopaminergic system in the pathogenesis of migraine. In this case report, we describe a syncopal episode in a patient with migraine without aura after the administration of a very low dose of apomorphine, a classical agonist of dopaminergic receptors. The absence of cardiovascular risk factors in this patient suggests that the clinical event might have been caused by hypersensitivity of the dopaminergic system. PMID- 7775181 TI - Cost-effectiveness of computed tomography in the evaluation of patients with headache. AB - We report a retrospective study to determine the cost-effectiveness of cranial computed tomography in patients with headache without neurological finding. Five hundred ninety-two neurologically normal patients were examined between 1990 and 1993 for the complaint of headache. Examination results were reevaluated from written report and image archive systems. Results were divided into three groups. In group P0, we included patients with normal cranial computed tomography findings. In group P1, patients showed some minor pathologies like ischemic or atrophic changes. These findings neither explained the reason for headache nor changed the clinical or therapeutic approach. The third group (P2) was to include patients with gross intracranial pathology like space-occupying lesions or bleeding. Five hundred forty-six of 592 patients were in the P0 group (92%), and the remaining 46 patients were in the P1 group (8%). No patient was found to have serious intracranial pathology detected by computed tomography. Cost of detection of a case with significant pathology was calculated. It is our opinion that computed tomography is an unrewarding technique in the evaluation of patients with chronic headache whose neurological examinations are normal. PMID- 7775183 TI - Chronic paroxysmal hemicrania in a child? PMID- 7775182 TI - Fluoxetine and migraine: comparison of double-blind trials. PMID- 7775184 TI - Standards of care. PMID- 7775185 TI - Headache and the human immunodeficiency virus type 1 infection. AB - This review focuses on the prevalence, causes, evaluation, and treatment of headache in individuals infected with human immunodeficiency virus type 1 (HIV 1). Headaches, one of the commonest medical complaints in the general population, occur frequently in patients infected with the HIV-1. HIV-related headaches can occur at any time during the infection: at seroconversion, during the incubation period, in patients with symptomatic HIV-1 infection, or after an AIDS-defining illness. Causes of HIV-related headaches include HIV-1 itself, opportunistic conditions, or HIV-specific medications. Migraines, tension-type headaches, depression, and substance abuse enter into the differential diagnosis, particularly in the early stages of disease. The headaches seen in this population reflect a complex web of interactions imposed by immune competency, multiple etiologies, treatments, and premorbid conditions. Prompt recognition and early treatment of headache is essential since it may improve quality of life and, depending on the diagnosis, prolong survival. Physicians need to be alert and adaptable when assessing HIV-infected individuals with headache since multiple causes can exist in the same patient and new syndromes, complications, and investigational drugs are continually being identified. PMID- 7775186 TI - Comparison of dihydroergotamine with metoclopramide versus meperidine with promethazine in the treatment of acute migraine. AB - Migraineurs often seek office-based treatment for acute headache. To compare the efficacy and side effect profile, we entered 27 migraineurs into a prospective, randomized, double-blind study where each patient received either 75 mg meperidine with 25 mg promethazine IM or .5 mg dihydroergotamine with 10 mg metoclopramide IV. After 1 hour, pain relief was similar in the two groups, but side effects were significantly greater in the meperidine with promethazine regimen group. The dihydroergotamine with metoclopramide regimen is effective, and has minimal side effects, making it an attractive method for office-based treatment of acute migraine. PMID- 7775188 TI - Whiplash around the world. AB - The term "whiplash" was first used in 1928 by the American orthopedist Crowe, although the earliest use that I can find published was in 1945 by the American orthopedist Davis. Although widely used by the medical profession and public, many physicians find the term objectionable. However, when used appropriately to refer only to the mechanism of injury in a motor vehicle accident, the term can be worthwhile. In any case, "whiplash" is well-entrenched in usage and is here to stay. But what term is used in other languages? Is there a term similar to "whiplash?" To determine terms for whiplash injuries in other languages, members of the American Academy of Neurology living in non-English-speaking countries were contacted by mail. Terms used in 11 other languages are listed. Some comments about whiplash injuries by respondents are excerpted. Further cross cultural studies may be helpful in studying the influence of physician and popular attitudes, as well as litigation on persistent neck complaints and headaches after motor vehicle accidents. PMID- 7775187 TI - Preventive effects of hyperbaric oxygen in cluster headache. AB - The effect of a 2-week course of hyperbaric oxygen on both the duration and frequency of cluster headache attacks was tested in four patients suffering from chronic cluster headache with no clear response to pharmacological treatments. Two patients (two courses in one case) dramatically improved while on hyperbaric oxygen treatment, this positive response remaining for 2 and 31 days posttreatment. Case 3 only improved in frequency, while the remaining patient showed no benefit. These findings suggest that daily hyperbaric oxygen treatment can be used as a transient preventive treatment for desperate cluster headache sufferers. PMID- 7775189 TI - Magnetic resonance imaging in migraine and tension-type headache. AB - Cerebral magnetic resonance imaging was performed on 63 patients with chronic primary headache (28 with migraine with and without aura, 35 with tension-type headache). Fifty-four headache-free individuals of the same age range were used as controls. The headache sufferers showed an incidence of focal white matter abnormalities on T2-weighted magnetic resonance imaging significantly higher than the age-matched control group (33.3% vs 7.4%). The incidence of white matter abnormalities did not correlate with age (except for patients older than 60 years), sex, headache history, headache status, or ergotamine consumption. Migraine (with and without aura) and tension-type headache patients had similar prevalence of white matter abnormalities (32.1% vs 34.3%). The lesions were predominantly distributed in the frontal region, independent of the side of usual aura or headache. Our findings indicate that both migraine and tension-type headache may be associated with early pathologic changes in the brain and may share, at least in part, common pathogenic pathways. PMID- 7775191 TI - Headache in a nonclinical population in Dar es Salaam, Tanzania. A community based study. AB - Headache is a common symptom that constitutes a major health problem to all countries in the world with a variable prevalence from about 20.2% in the African population to about 80% in populations of the civilized world. Community-based studies in African populations are still scanty, and the impact on health facility utilization and sickness absence from work is unknown. After a simple random selection, 1540 urban workers and students of higher education completed a standardized self-administered questionnaire on headache. A total of 815 (52%), (620 (51%) men, 195 (60%) women) admitted to having suffered a headache requiring medication or medical consultation in the last year. Of these, 366 (23.7%) had recurrent headache not attributable to systemic disease. Of the total with recurrent headache, there was a significant preponderance of women over men with sex prevalence of 28.9% and 22.4%, respectively (X2 P = 0.0001). Combined vascular-muscular-type of headache exceeded all types of headache, accounting for 35.8% of cases, followed by migraine accounting for 30.8% of cases. Organic disease was rare, accounting for 8.5% of cases, and psychogenic causes of headache were even rarer at less than 1.2% of cases. Within 2 months of onset of recurrent headaches, over 32% of sufferers had utilized the health facility at their place of work or study. A significant number of cases (175) had an average of 11.3 lost work days per year in comparison to a control group of 154 persons with an average of 5.7 lost work days per year for reasons other than headache (X2 P = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775190 TI - Improvement of decreased critical flicker frequency (CFF) in headache patients with drug abuse after successful withdrawal. AB - A considerable proportion of headache patients fulfill the criteria of "drug abuse" (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis. The present study deals with the question whether this impairment of vigilance and continuous performance is reversible. Forty-eight headache patients with drug abuse were investigated three times by means of CFF analysis: immediately before (A), immediately after (B), and 3 weeks after having finished (C) inpatient drug withdrawal. Immediately after withdrawal, a significant decrease of headache intensity was observed. The CFF values, however, remained unchanged at a depressed level, probably due to withdrawal medication and the initial sedative side effects of thymoleptic agents (given as prophylaxis). Three weeks after withdrawal, however, the CFF values were significantly improved, and were now within a range not far from the normal values known from a healthy general population. Thus, even after many years of drug abuse, headache patients have a good chance to improve their vigilance and continuous performance and to reach normal or close to normal levels. PMID- 7775192 TI - Intranasal capsaicin for acute abortive treatment of migraine without aura. PMID- 7775193 TI - Postconcussion syndrome. PMID- 7775195 TI - Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma. AB - The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance. PMID- 7775197 TI - Immunohistochemical demonstration of the carbonic anhydrase isoenzymes I and II in pancreatic tumours. AB - The location of carbonic anhydrase (CA) isoenzymes I, II and VI in normal and neoplastic pancreatic tissue was studied using polyclonal antisera and the immunoperoxidase technique. Samples were obtained from patients with well differentiated (n = 4), moderately differentiated (n = 1) and poorly differentiated (n = 4) ductal adenocarcinomas, cystadenocarcinoma (n = 2), adenosquamous carcinoma (n = 1), acinar adenocarcinoma (n = 1), gastrinoma (n = 3), insulinoma (n = 3) and glucagonoma (n = 1). The control specimens were from a patient with traumatic laceration of the pancreas. The normal and malignant endocrine tissue showed intense positive staining for CA I localized in the cells expressing glucagon. In the exocrine pancreatic tissue, CA II was detected in the normal and neoplastic ductal epithelium. No specific staining was detected with anti-CA VI serum in either normal or malignant tissue. PMID- 7775196 TI - Distribution and quantification of alpha 1-integrin subunit in rat organs. AB - The alpha 1 beta 1-integrin is known to be a receptor for collagen and laminin mediating cell-matrix interactions. A monoclonal antibody, 33.4, which specifically inhibits the alpha 1-integrin-mediated in vitro cell-collagen binding of rat hepatocytes and hepatoma-derived A-cells (Loster et al., 1994), was used to purify by immunoaffinity chromatography the alpha 1-integrin subunit from rat liver in large quantities for inducing a polyclonal antiserum. In immunoblot analysis on membrane extracts of several rat organs this polyclonal antiserum recognized only a 190 kDa-band, suggesting that it is highly specific for the alpha 1-integrin subunit. A sandwich-ELISA with monoclonal antibody 33.4 and the polyclonal antiserum against the alpha 1-integrin subunit, respectively, enabled the quantitative expression pattern of the alpha 1-integrin subunit to be studied in different rat organs. With the exceptions of brain (not detectable) and muscle (low concentration), the alpha 1-integrin subunit was detectable in almost all organs of the digestive, respiratory and urogenital system as well as in lymphatic organs. The highest relative concentrations of alpha 1-integrin subunit were found in uterus, lung and spleen, whereas in seminal vesicle, stomach, parotid gland, epididymis, kidney and liver only modest concentrations were evident. The organ distribution and localization of alpha 1-integrin subunit were studied by immunohistochemistry with monoclonal and polyclonal antibodies. Immunoreactivity was present in the plasma membranes of all smooth muscle cells, vascular endothelial cells of many organs and fibrocyte-fibroblast sheaths in the heart and kidney. Since these cells are in close contact with collagen-containing basal membranes as well as reticular fibrils, strong evidence exists that in rat tissues the alpha 1-integrin subunit is expressed at sites where collagen is present and might be involved in vivo in cell-collagen binding. PMID- 7775194 TI - Analysis of enzyme reactions in situ. AB - Estimations of metabolic rates in cells and tissues and their regulation on the basis of kinetic properties of enzymes in diluted solutions may not be applicable to intact living cells or tissues. Enzymes often behave differently in living cells because of the high cellular protein content that can lead to homologous and heterologous associations of protein molecules. These associations often change the kinetics of enzymes as part of post-translational regulation mechanisms. An overview is given of these interactions between enzyme molecules or between enzyme molecules and structural elements in the cell, such as the cytoskeleton. Biochemical and histochemical methods are discussed that have been developed for in vivo and in situ analyses of enzyme reactions, particularly for the study of effects of molecular interactions. Quantitative (histochemical) analysis of local enzyme reactions or fluxes of metabolites has become increasingly important. At present, it is possible to calculate local concentrations of substrates in cells or tissue compartments and to express local kinetic parameters in units that are directly comparable with those obtained by biochemical assays of enzymes in suspensions. In situ analysis of the activities of a number of enzymes have revealed variations in their kinetic properties (Km and Vmax) in different tissue compartments. This stresses the importance of in vivo or in situ analyses of cellular metabolism. Finally, histochemical determinations of enzyme activity in parallel with immunohistochemistry for the detection of the total number of enzyme molecules and in situ hybridization of its messenger RNA allow the analysis of regulation mechanisms at all levels between transcription of the gene and post-translational activity modulation. PMID- 7775198 TI - Histochemical differences of the lectin affinities of backbone polylactosamine structures carrying the ABO blood group antigens in papillary carcinoma and other types of thyroid neoplasm. AB - Endo-beta-galactosidase from Escherichia freundii cleaves linear polylactosamine structure as follows: R-GlcNAc-beta 1-3Gal-beta 1-4GlcNAc-beta 1-R' + H2O-->R GlcNAc-beta 1-3Gal + GlcNAc-beta 1-R'. Staining with Griffonia simplicifolia agglutinin II (GSA-II) following enzyme digestion reveals the distribution of R GlcNac-beta 1-3Gal-beta 1-4GlcNAc-beta 1-R' structures in tissue sections. In this study, the procedure was applied to formalin-fixed, paraffin-embedded tissue sections from 26 cases of papillary carcinomas including 2 follicular variants, 8 follicular carcinomas, 7 adenomas, 1 anaplastic carcinoma and 1 medullary carcinoma in order to investigate whether different types of polyactosamine containing structure are produced in these thyroid neoplasms. Simultaneously, the susceptibility of the ABH antigens expressed in these neoplastic cells to endo beta-galactosidase digestion was examined. Most of the papillary carcinoma cells from all the individuals examined were strongly stained by GSA-II following enzyme digestion. Without enzyme digestion, little or no reactivity with GSA-II was observed. Among other types of neoplasms, only one case of follicular carcinoma exhibited reactivity with GSA-II following enzyme digestion. ABH antigens were expressed in 22 cases of papillary carcinomas, 2 adenomas, 5 follicular carcinomas and 1 anaplastic carcinoma, and their expression was dependent on the ABO blood group of the patients. Endo-beta-galactosidase digestion resulted in the elimination of these antigens not only in papillary carcinomas but also in other neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775199 TI - Wet autoclave pretreatment for immunohistochemical demonstration of oestrogen receptors in routinely processed breast carcinoma tissue. AB - The immunohistochemical demonstration of oestrogen receptor (OR) was performed on 32 randomly selected and routinely processed breast carcinomas after wet autoclave pretreatment of sections. The autoclave method was compared to the OR status found on frozen sections as well as to alternative pretreatment methods such as enzymatic predigestion and microwave irradiation. Using four different monoclonal antibody clones (H222, LH1, CC4-5, 1D5.26), the OR status was evaluated for each of the various pretreatment methods applied. All cases with a high OR content on frozen sections (n = 11) also showed a high OR status on wet autoclave-pretreated paraffin tissues using antibody clones 1D5.26 and CC4-5; in cases with low OR content on frozen sections, no false-negative cases were recorded using only the antibody 1D5.26 neither after wet autoclave nor microwave pretreatment. In addition, with this antibody, OR was detectable after autoclave pretreatment in two cases which were considered to be OR-negative even on frozen sections. When the primary antibody was omitted, no false-positive cases were observed after wet autoclave pretreatment. Thus, in our hands, wet autoclave pretreatment, in combination with the antibody 1D5.26, offers a highly sensitive method for the immunohistochemical demonstration of OR in routinely formalin fixed, paraffin-embedded sections of breast carcinomas. PMID- 7775200 TI - Immunohistochemical detection of oncoprotein 18 (Op18) in malignant lymphomas. AB - Expression of oncoprotein 18 (Op18), an intracellular phosphoprotein up-regulated in many malignant cell types, was evaluated in a series of normal lymphoid tissue and malignant lymphomas. In normal tonsils and reactive lymph nodes, the majority of Op18-positive cells were present in the germinal centres, whereas cells in the mantle zone were essentially negative and the interfollicular areas showed occasional positive cells. Double staining for PCNA and Op18 revealed that Op18 expression only to some extent was correlated with cell proliferation, as determined by PCNA expression. Non-Hodgkin's lymphomas exhibited a variable Op18 expression, and in Hodgkin's disease, Reed-Sternberg and Hodgkin cells frequently expressed Op18 with a strong staining intensity. Using Op18-PCNA double staining in malignant lymphomas, Op18 expression could also be partially dissociated from cell proliferation. By using confocal microscopy, the intracellular localization of Op18 was studied, demonstrating diffuse reactivity in the cytoplasm in interphase cells and during mitosis, whereas nuclei and condensed chromosomes were negative. In conclusion, Op18 was expressed at variable levels in most, perhaps all, proliferating lymphocytes in benign lymphoid tissue as well as in malignant lymphomas. However, the Op18 protein was also detected in a significant fraction of apparently non-cycling normal and neoplastic lymphocytes. PMID- 7775202 TI - Widowhood: a painful intrusion into the analytic space. PMID- 7775201 TI - Distribution of vasoactive intestinal peptide-like immunoreactivity in the taste organs of teleost fish and frog. AB - Using immunohistochemistry, vasoactive intestinal peptide (VIP) was visualized in taste bud cells of the carp, Cyprinus carpio, and the European catfish, Silurus glanis, by means of light and electron microscopy. Intracellular membrane systems, presumably smooth endoplasmic reticulum, of light (sensory) cells, but not of dark (supporting) cells and basal cells, were densely labelled with antibody. In the frog (four species: Rana temporaria, R. ridibunda, R. arvalis, R. pipiens), taste bud cells did not label. However, the dense basal nerve fibre plexus, some subepithelial ganglionic cells, but no ascending intragemmal fibres, were immunoreactive. In fish, the results support evidence that VIP is involved in the modulation of taste transduction at the level of receptor cells. In the frog, an indirect, possibly vasodilatatory effect on taste perception may be considered. PMID- 7775203 TI - Psychoanalytic theories of infant differentiation of self and other. AB - Traditional psychoanalytic theories of infancy were challenged a number of years ago by Peterfreund (1978) and Milton Klein (1980), but published debate on this issue has only recently begun to appear. The main purpose of this paper is to respond to Zuriff's (1992) argument that new data from recent observational research on infants fails to refute earlier theories of infancy. The following quote from Zuriff is a good introduction to the topic: "For many years, a frequent and consistent criticism of psychoanalytic theory is that it is not testable (Nagel, 1959; Popper, 1962). That is, no matter what the evidence, psychoanalytic theories can always be maintained because they are too vague, incomplete, and indeterminate to be falsified. Yet, in the area of contemporary psychoanalytic theory of infancy, we seem to have a counterexample to this criticism. Supporters of the new theories claim that the experimental evidence refutes older psychoanalytic notions of infancy, such as normal autism and symbiosis, and establishes a different model, that of the 'competent infant.'" (p. 19). PMID- 7775204 TI - The impact of psychoanalytic values on transference and countertransference: a study in transcultural psychotherapy. AB - In transcultural psychoanalytically oriented treatments, the therapist must consider differences between the cultures of origin of both patient and therapist. The therapist also must be aware of a third relevant culture that affects the patient-therapist dyad: the psychoanalytic culture. The effect of the psychoanalytic culture and its values on the development of transference and countertransference is illustrated in three clinical vignettes from transcultural treatments. The authors offer suggestions for dealing with problems that arise because of discrepancies between the psychoanalytic cultural values and the patient's cultural values. PMID- 7775206 TI - Leopold von Sacher-Masoch and masochism. PMID- 7775205 TI - Regression and reparation in religious experience and therapy. PMID- 7775209 TI - A view of the moral landscape of psychoanalysis. PMID- 7775207 TI - From the ecclesiastical to the profane: foot fetishism in Luis Bunuel and Alain Robbe-Grillet. PMID- 7775208 TI - Psychoanalysis and faith. PMID- 7775210 TI - The Oedipus complex: some observations and questions regarding its validity and universal existence. PMID- 7775212 TI - Special issue based on a symposium on Developmental Psychophysiology at the 7th International Congress of Psychophysiology of the International Organization of Psychophysiology. Porto Carras, Macedonia, Greece, 27 September-2 October 1994. PMID- 7775211 TI - Substance abuse: the role of depression and trauma--a case report. AB - Substance abuse is associated diagnostically with existing depression, pathological mourning of the traumatic event itself, with the inevitable experience of object loss, and loss of love. Inability to form object representation insures primitive lack of object constancy, resulting in pre oedipal longing and neediness and malignant affect. Ambivalence towards the sadistic love objective is recognized and allows for a healthier, more complete period of mourning (Freud, 1917). Indeed, depression is banished from family acknowledgement in the service of homeostatic denial. This only reinforces the identified patient's feeling of unreality, shame and guilt over verbalizing the depression and the frequent underlying traumatic history. The enormous role of socio-economic stress is pervasive, yet the focus here is on individuals with complex dynamic constellations which are often ignored in the face of external factors. Addiction as attempt to self-medicate depression and trauma remains the overarching theme. PMID- 7775214 TI - Syndromes of schizophrenia and schizotypy, hemispheric imbalance and sex differences: implications for developmental psychopathology. AB - Progress is reviewed on the elucidation of the neuro-psychophysiological basis of a three-syndrome model of symptom expression in schizophrenia (Active, Withdrawn, Unreality), the first two syndromes of which were associated with an imbalance in activity between the hemispheres (Gruzelier, 1984). Recent work has discovered a similar three-syndrome structure to schizotypy in the normal population, and in keeping with the activation connotations of the Active and Withdrawn syndromes differences on self-report arousal scales were found. The same syndromes in normals were also associated with handedness, unlike the third Unreality syndrome which cognitive measures have shown to be inconsistently lateralised. Gender is known to be of fundamental importance to the form and expression of schizophrenia. Here sex differences had an important bearing on the syndrome hemispheric imbalance relations which were stronger in males, while females had higher scores on the Unreality syndrome. Cognitive asymmetry patterns measured with recognition memory tests of lateralised temporoparietal functions disclosed a word > face cognitive asymmetry in females and a face > word asymmetry in males; asymmetries which were found to characterise androgynous individuals and feminine males. The results are in keeping with the relevance of the temporoparietal region to sexual dimorphism in brain structure and function, and by virtue of hippocampal connections, possible influences of hormones on brain development. PMID- 7775215 TI - Sex and occupation as markers for task performance in a dichotic measure of brain asymmetry. AB - The present experiment tested dichotic listening performance in four groups of subjects: males and females working in occupations carried out most commonly by males, and males and females working in occupations most commonly carried out by females. It was hypothesized that both males and females in male-typical occupations would produce a similar pattern of performance in a dichotic task, that is, they would produce a marked right ear advantage (REA), reflecting a more asymmetric hemisphere organisation, while males and females in female-typical occupations would show a reduced REA reflecting less asymmetrically distributed underlying neural structures. The experimental results supported the hypothesis and are interpreted as support for a dimensional view of neurological sexual differentiation. PMID- 7775213 TI - New directions in developmental psychopathology. PMID- 7775216 TI - The maturational theory of brain development and cerebral excitability in the multifactorially inherited manic-depressive psychosis and schizophrenia. AB - An association has been established between the multifactorially inherited rate of physical maturation and the final step in brain development, when some 40% of synapses are eliminated. This may imply that similarly to endocrine disease entities, we have cerebral disease entities at the extremes of the maturational rate continuum. The restriction of prepubertal pruning to excitatory synapses leaving the number of inhibitory ones fairly constant, implies changes in cerebral excitability as a function of rate of maturation (age at puberty). In early maturation there will be an excess in excitatory drive due to prematurely abridged pruning, which compounds a synchronization tendency inherent in excessive synaptic density. Lowering excitatory level with antiepileptics is hypothesized to be a logical treatment in this type of brain dysfunction. In late maturation, a deficit in excitatory drive due to failure to shut down the pruning process associated with a tendency to the breakdown of circuitry and desynchronization, adds to a similar adversity inherent in reduced synaptic density. Raising the excitatory level with convulsants is hypothesized to be the treatment for this type of CNS dysfunction. The maturational theory of Kraepelin's psychoses holds that they are naturally occurring contrasting chemical signaling disorders in the brain at the extremes of the maturational rate continuum: manic depressive psychosis is a disorder of the early maturer and comprises raised cerebral excitability and a raised density of synapses. This is successfully treated with anti-epileptics like sodium valproate and carbamazepin. Schizophrenia is a disorder in late maturation with reduced cerebral excitability and reduced synaptic density. This is accordingly treated with convulsants such as typical and atypical neuroleptics. However, the conventional effective treatments in both disorders act on inhibition only by either lowering or raising inhibitory level. While the neuroleptics drugs are superior anti-psychotics they nevertheless do not affect the deviation in cerebral excitability which would explain why they do not cure. Disturbed circadian rhythms which precede psychotic episodes in manic depressives accord with a primary dysfunction in the CNS, the suprachiasmatic nucleus of the hypothalamus via its direct input the glutamatergic retinohypothalamic tract. The residual deficits in schizophrenia accord with persistently disconnected circuitry and communication which is a consequence of reduced excitatory level and is manifested in insufficient motivation, a reduced drive associated hypofunction, and neuromuscular dysfunction. PMID- 7775217 TI - Deviation in cerebral excitability: possible clinical implications. AB - Schizophrenia, a chemical signaling disorder in the brain, is also a deteriorating neurological disorder. The deficit in cerebral excitability, and associated reduced synaptic density, imply a risk of cortical breakdown of circuitry accompanied by an insufficient fill-in mechanism, and persistent silent spots, but no total loss of function, only dysfunction. This is subjectively experienced as deficiencies of cognition, perception and sensorimotor phenomena depending upon localization and connections of the disconnected circuitry. Considering the adversity inherent in this neural network, both the fast Hebbian pre-post form of learning and the slow pre-modulatory coincidence form of learning are probably impaired. The use of Feed Back Loops which usually govern our behaviour might also be impaired. In addition, we have to consider the daily problem of insufficient drive and motivation. Manic depressive psychosis, a chemical signaling disorder in the brain, is a true functional psychosis. The raised excitatory drive and raised synaptic density imply raised risk of uncoupling of circadian rhythms via the direct glutamatergic input to the suprachiasmatic nucleus of hypothalamus (SCN). This episodic brain stem dysfunction illustrates how a deficit in inhibition renders the brain unstable. The requirements of the fast Hebbian form of learning should easily be met, and neither should the slow forms of learning present a problem in networks characterized by excessive density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775218 TI - Functional brain asymmetry, handedness and menarcheal age. AB - Functional brain asymmetry influences many functions of the organism; the neuroendocrine axis is one that has received insufficient attention. In this study we set us as the goal of studying the link between functional brain asymmetry and menarcheal age in females with left versus right manual dominance. The appearance of the first menarche was used as a natural model of functioning of the hypothalamic-pituitary-gonadal (HPG) axis. 1695 females, aged between 16 and 25 years, were interviewed by questionnaire about manual dominance and menarcheal age. 182 women were selected and divided into 2 groups: all left handers (n = 91), and a control group of 91 right-handers. We found a significantly lower average age of menarcheal appearance in the left-handers' age of 12.09 +/- 0.16 years compared to the right-handers' age of 13.32 +/- 0.12 years (p < 0.001). The earliest menarcheal age in left-handers was 8 years and the peak of appearance at age 13 (in 30.76% of the cases). In right-handers these values were 10 and 14 years (in 40.60% of the cases), respectively. The data allow us to accept the existence of a link between functional brain asymmetry and menarche, which causes earlier activation of the HPG axis in left-handed females. PMID- 7775219 TI - Patterns of cognitive asymmetry and psychosis proneness. AB - We previously reported evidence in university students of three syndromes of schizotypy which have strong affinities with three-syndrome models of schizophrenia. As in schizophrenia two of the syndromes were associated with opposite hemispheric asymmetry patterns: an Active syndrome with a left > right asymmetry, and a Withdrawn syndrome with a right > left asymmetry. The third Unreality syndrome bore no consistent relation to pattern of asymmetry. Cognitive asymmetry was measured by comparing recognition memory for words with memory for unfamiliar faces using a neuropsychological test which assesses temporoparietal functions. Here the same approach was extended to the broader concept of psychosis proneness with a new inventory with four subscales: Introvertive Anhedonia, Impulsive Nonconformity. Unusual Experiences, and Cognitive Disorganisation. In support of the relevance of an activation dimension to cognitive asymmetry, Impulsive Nonconformity was associated with word > face superiority, as was a self report measure of Energy. Introvertive Anhedonia was associated with face > word superiority. As in schizophrenia these predicted asymmetry relations were significant in males only. Neither the Unusual Experiences nor Cognitive Disorganisation subscales were associated with cognitive asymmetry. PMID- 7775220 TI - Visual processing, lateralization and syndromes of schizotypy. AB - There is an association between positive features of schizotypy and dyslexia, largely involving distortions of visual and auditory perception and associated cognitive anomalies. In dyslexia, there is strong evidence for a disorder of subcortical magnocellular pathways, which may underlie these perceptual aberrations. Here we investigated visual processing in relation to three syndromes of schizotypy-Active, Withdrawn and Unreality-in normal adults, using a "dot localization" test of visual direction sense on which dyslexics perform poorly, and which should be sensitive to magnocellular dysfunction. Results showed that increased error scores were associated with both the positive syndromes, Active and Unreality, which in this study were highly correlated. There were also interactions between each syndrome and the direction of errors, such that high scorers on the Unreality and Active syndromes made more errors on leftward trials, while high Withdrawn subjects made fewer left and more right errors. Mixed handers also showed poorer performance than consistent handers. The evidence of poor visual direction sense in relation to positive syndromes of schizotypy and mixed handedness is consistent with the previous results for dyslexics, who also show these features. The opposite lateralization of errors in the positive v negative syndromes of schizotypy is in keeping with the model of hemisphere imbalance and patterns of cognitive asymmetry which distinguish Active from Withdrawn syndromes. These results are considered in relation to the proposal that a disorder of magnocellular function may underlie the perceptual distortions which are common to dyslexia and positive syndromes of schizotypy. PMID- 7775221 TI - Developmental dyslexia, neural timing and hemispheric lateralisation. AB - Approximately 5% of 8-10-year-olds experience exceptional difficulties learning to read (developmental dyslexia). This usually has a congenital basis; it runs in families, and affects 4 times as many boys as girls. Dyslexics typically show impairment both in phonemic segmentation (the subdivision of speech beyond the natural syllabic level) and in sequencing small visual symbols. Both these skills draw upon the ability of the nervous system to time sensory events precisely. A specific magnocellular cell type which expresses a distinctive surface antigen plays a crucial role in these functions. The development of this cell line is probably congenitally impaired in dyslexics. Visually they have lowered flicker and motion sensitivity, and disorder of the magnocellular layers of the Lateral Geniculate Nucleus can be seen post mortem. Likewise they have lowered sensitivity to changes in frequency and amplitude of sounds, hence impaired discrimination of speech sounds. These disorders are associated with abnormal hemispheric lateralisation in these subjects, e.g. dyslexics show reduction or reversal of the usual left > right asymmetry of the planum temporale. Many of these characteristics of impaired magnocellular function and reversed hemispheric asymmetry are found not only in dyslexic children but also in developmental dysphasics, autistics, high schizotypes and schizophrenics. I will speculate therefore that normal magnocellular development promotes normal hemispheric asymmetry and that impaired magnocellular development is responsible for a spectrum of problems associated with impaired hemispheric specialisation, ranging from the mildest, dyslexia, to the most severe, schizophrenia. PMID- 7775222 TI - Dyslexia, handedness and syndromes of psychosis-proneness. AB - In an earlier study, adult dyslexia was found to be strongly associated with positive schizotypal traits, and particularly with unusual perceptual experiences. However, recent evidence suggests that the structure of psychosis proneness in normals may involve three or four distinct yet related dimensions. Therefore a further study was conducted, using a wider range of measures, to explore associations between dyslexia and these different syndromes of psychosis proneness. Relationships with handedness were also investigated. If three syndromes of psychosis-proneness were delineated, broadly corresponding to "Active", "Withdrawn" and "Schneiderian/Unreality" syndromes of schizophrenia, dyslexics showed elevations on both positive syndromes (Active and Unreality), but not on the negative, Withdrawn syndrome. With a four-factor model only one dimension, perceptual/cognitive anomalies, distinguished dyslexics from controls. These findings confirm an association between dyslexia and positive, but not negative, schizotypal traits. Mixed-handedness was strongly associated with dyslexia, and in controls with those measures of psychosis-proneness involving unusual perceptual experiences. This suggests that reduced lateralization may be a feature common to both dyslexia and the Unreality syndrome of schizotypy, which may help to account for the strong relationship between them. PMID- 7775223 TI - Auditory event-related potentials, dichotic listening performance and handedness as indices of lateralisation in dyslexic and normal readers. AB - Evidence suggests that children with developmental dyslexia have poor phonological processing skills, are less likely to show lateralised activation during the processing of verbal information than children with normal reading ability and tend towards the left of the handedness continuum. The present study investigated this relationship between cerebral lateralisation and reading ability in children with and without dyslexia, directly using a dichotic listening paradigm with contemporaneous recording of auditory evoked potentials and indirectly using measures of hand preference and hand skill. The two groups were significantly different on a phonemic awareness task, particularly with reference to rime rather than phoneme onset. The two groups performed equally well on the dichotic listening task. However, normal readers produced significantly greater N100 amplitudes in the left temporal region during dichotic listening than the dyslexics who displayed approximately equivalent levels of amplitude bilaterally. In terms of hand preference the dyslexics were significantly less right-hand preferent than the controls, although the groups did not differ on a measure of right/left hand skill. The AEP lateralisation indices and the hand preference scores were significantly related to phonemic awareness performance. The different patterns of AEP activity produced by the two groups of children during the dichotic listening task and the differences in hand preference may be related to abnormal cerebral lateralisation of language functions. The failure of the dichotic listening task to discriminate between the two groups in spite of evidence of differences in cortical activation suggests that the processing difficulties which may be indexed by these differences in cortical activation affect the reading process at a later stage than that tapped by dichotic listening. PMID- 7775224 TI - Humankind's uses of animals. PMID- 7775225 TI - Food safety considerations. PMID- 7775226 TI - Vagal indigestion. PMID- 7775227 TI - Earth Day participants slap the hand that feeds them. PMID- 7775228 TI - The ethics and etiquette of good gossip. PMID- 7775229 TI - What is your diagnosis? Rodenticide toxicosis causing soft tissue swelling ventral to the hyoid bones and larynx. PMID- 7775230 TI - Trends in veterinarians' professional income, 1983 to 1993. PMID- 7775232 TI - Results of surgery and doxorubicin chemotherapy in dogs with osteosarcoma. AB - Thirty-five dogs with appendicular osteosarcoma were treated with 5 doses of doxorubicin (30 mg/m2 of body surface, i.v., every 2 weeks). Surgical excision of the primary tumor was performed 13 days after the second (n = 18) or third (n = 17) treatment, and the subsequent doxorubicin treatment was given the day following surgery. Resected tumors were evaluated histologically to determine response to preoperative chemotherapy (ie, percentage of the tumor that was necrotic). Survival data for the 35 dogs were compared with survival data for a historical control group, consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Administration of doxorubicin at 2 week intervals was well tolerated. Three dogs were alive and did not have evidence of disease at the time of reporting. Of the remaining 32 dogs, 3 died or were euthanatized because of cardiomyopathy presumably caused by doxorubicin; 1 died suddenly 116 weeks after initiation of treatment; and the remaining 28 were euthanatized because of problems documented to be related to distant metastases. Thirteen dogs (40.6%) were euthanatized because of pulmonary metastases, 10 dogs (31.3%) were euthanatized because of bone metastases, and 5 dogs (15.6%) were euthanatized because of metastases in other sites. The proportion of dogs euthanatized because of bone metastases was significantly (P < 0.001) higher for the study group than for the control group. Median survival time for the 35 dogs that received doxorubicin was estimated to be 52.3 weeks, and 1- and 2-year survival rates were estimated to be 50.5 and 9.7%, respectively. Survival time was significantly (P < 0.0001) longer for these dogs than for control dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775231 TI - Efficacy of, and toxicoses associated with, oral idarubicin administration in cats with neoplasia. AB - Idarubicin, a new synthetic anthracycline analogue, was administered orally to 34 cats with spontaneous tumors. The maximum tolerated dosage was determined to be 2 mg/cat/d given for 3 consecutive days every 3 weeks. Anorexia and leukopenia were found to be dose limiting in cats receiving the drug at a higher dosage. The most common toxicoses seen at the maximum tolerated dosage were leukopenia, anorexia, and vomiting; however, development of toxicoses was not found to be associated with sex, FeLV test result, tumor type, dosage, age, or weight. Idarubicin (2 mg/cat/d for 3 days, q 3 wks) was used to treat 18 cats with lymphoma in which complete remission had been achieved by administration of other chemotherapeutic agents. Median remission duration for these cats was comparable to that reported for cats treated with other protocols. We concluded that orally administered idarubicin would be useful in the treatment of cats with lymphoma. PMID- 7775233 TI - Chylothorax associated with constrictive pericarditis in a dog. AB - Chylothorax was associated with constrictive pericarditis in a 6-year-old mixed breed dog. Clinical signs included hepatomegaly, bilateral jugular pulses, muffled heart sounds, and dyspnea. Pleural effusion was identified on thoracic radiographs. Thoracentesis yielded 3 L of chylous effusion, confirmed by the cholesterol/triglyceride ratio (0.14). Echocardiography revealed a thickened pericardium, with numerous fibrin tags, which was suggestive of constrictive pericarditis. Central venous, right atrial, and right ventricular pressures were high and on right ventricular diastolic pressure tracings, the square-root sign, which is indicative of constrictive pericarditis, was evident. Exploratory thoracotomy and pericardiectomy were performed. Histopathologic findings were consistent with chronic non-suppurative pericarditis. The dog's condition improved after surgery. On reevaluation 11 months later, central venous pressure and results of physical examination and thoracic radiography were normal. On the basis of these findings, we concluded that chylothorax was caused by constrictive pericarditis in this dog. Chylothorax is often associated with disorders that have a poor prognosis, but if constrictive pericarditis can be identified as the cause of the chylothorax, exploratory thoracotomy and pericardiectomy can provide a cure. PMID- 7775234 TI - Hyperkalemia associated with potassium chloride administration in a cat. AB - Addition of appropriate amounts of potassium chloride solution to fluid administered i.v. resulted in hyperkalemia in a cat. To evaluate whether incomplete mixing of potassium chloride in the fluid might have resulted in the observed hyperkalemia, 40 mEq (20 ml) of potassium chloride solution was injected into each of three 1-L vinyl bags of 5% dextrose in water, with or without attempting to mix the additive with the fluid in the bag. Measurement of potassium concentrations in the bags revealed that injecting potassium chloride solution into a bag of fluid while that fluid is being administered can result in incomplete mixing and discharge of concentrated potassium chloride from the administration set. The greatest potassium concentration measured in fluid sampled from the administration set was 194 mEq/L. PMID- 7775236 TI - Glioma in a goat. AB - An adult goat was examined because of behavioral changes and circling. Results of neurologic examination, CSF analysis, hematologic evaluation, and computed tomography of the brain were suggestive of an intra-axial mass. The goat was euthanatized because of worsening neurologic condition and poor prognosis. Necropsy revealed a large mass in the right cerebral hemisphere and caudal brain herniation through the foramen magnum. The mass was diagnosed as a glioma, with oligodendrocyte differentiation. Results of immunohistochemical evaluation were compatible with a malignant, poorly differentiated tumor. PMID- 7775235 TI - Use of mesenteric lymphangiography in a calf with chylothorax and chyloperitoneum. AB - Lymphatic abnormalities resulting in chylous effusion into a body cavity are uncommon in domestic animals. In a 6-day-old calf admitted to our hospital because of failure to suckle and abdominal distention, however, mesenteric lymphangiography revealed an obstruction of lymphatic flow. Laparoscopic examination of the abdomen was unsuccessful. Fluid accumulation was resolved in this calf by drainage. In cattle with chylothorax and concurrent chyloperitoneum in which a traumatic lesion of the thoracic duct is possible, conservative management, with drainage and supportive treatment, should be attempted prior to considering surgical intervention. PMID- 7775237 TI - Effect of surgical removal of subcutaneous tumors on survival of rats. AB - Mammary and other subcutaneous tumors were surgically removed from aged Sprague Dawley rats in an attempt to extend survival. The surgical technique was straightforward, and survival following mastectomy was good (17/21). The number of mammary and pituitary tumors in sexually intact rats and those that had previously undergone ovariectomy were compared. The frequency of mammary tumors was significantly lower in ovariectomized vs sexually intact rats (2/47 vs 24/49), as was the frequency of pituitary adenomas (2/46 vs 27/41). Survival to 630 days of age was higher in ovariectomized than in sexually intact rats (42/47 vs 29/49), although tumors did not contribute significantly to mortality. PMID- 7775238 TI - Uveal malignant melanoma in a duck. AB - An adult male Muscovy (Cairina moschata) X Peking (Anas platyrhynchos) duck had a primary malignant uveal melanoma with periocular extension involving the left eye. The periocular mass displaced the globe 1.5 cm laterally. Thoracic metastasis of the ocular neoplasm infiltrated the pectoral muscles, rib cage, and cranial lung lobe on the left side, causing diminished voluntary motion of the left wing. The left orbit was exenterated, but tumor regrowth was evident within 2 weeks. This case was unusual because melanocytic neoplasms are rare in birds. PMID- 7775239 TI - Escherichia coli O157:H7. PMID- 7775241 TI - Chronicles of a feisty public health veterinarian. PMID- 7775240 TI - More information on hematologic characteristics of greyhounds. PMID- 7775242 TI - Pathogenesis of bluetongue virus infection of cattle. PMID- 7775243 TI - What is your diagnosis? Intracranial cavitary lesion. PMID- 7775244 TI - What is your neurologic diagnosis? An atypical case of diskspondylitis caused by Aspergillus spp. PMID- 7775245 TI - The limits of confidentiality: a veterinarian's duty to report disease, cruelty, and theft. PMID- 7775246 TI - Plasmid profiles and resistance to antimicrobial agents among Salmonella enteritidis isolates from human beings and poultry in the midwestern United States. AB - In the study reported here, 121 Salmonella enteritidis isolates from human beings and 467 isolates from nonhuman sources were analyzed for plasmid pattern and susceptibility to a panel of antimicrobial agents commonly used as biologic markers. A significant (P < 0.05) number of isolates from nonhuman sources were resistant to beta-lactam antibiotics and tetracycline. Resistance to aminoglycosides, quinolones, and trimethoprim/sulfamethoxazole was uncommon. Of the 588 isolates, 445 (76%) were resistant to 2 or more antimicrobial agents. Sixty of 121 (50%) S enteritidis isolates from human beings were susceptible to all 12 antimicrobial agents, but 425 of 467 (91%) S enteritidis isolates from nonhuman sources expressed resistance to 1 or more of the antimicrobial agents used in the study. Analysis of plasmid profiles revealed that significantly (P < 0.05) more isolates from nonhuman sources had high molecular weight plasmids than did isolates from human beings. Isolates from ceca of chickens were associated with patterns of low molecular weight plasmids. Analysis of results of the study revealed similarities among S enteritidis from human beings and eggs, as determined on the basis of plasmid profiles and antibiotic susceptibility patterns, which may implicate eggs as one of the potential sources for infection of human beings. In addition, periodic monitoring of a substantial number of Salmonella isolates to detect drug resistance may be a prudent practice for use in revising the list of antimicrobial agents commonly used in human beings and other animals. PMID- 7775247 TI - Evaluation of results of preoperative urodynamic measurements in nine dogs with ectopic ureters. AB - Cytometrographic studies and urethral pressure profiles were performed to objectively assess the functional status of the urinary bladder and urethra in 9 dogs with congenital ectopic ureters. Functional abnormalities of the urinary bladder or urethra were detected in 8 of 9 (89%) dogs. Cystometrographic evidence of reduced bladder capacity was detected in 4 (44%) dogs, and abnormalities in urethral pressure profiles were consistent with urethral incompetence in 6 (67%) dogs. Dogs with urethral pressure profile abnormalities were treated with phenylpropanolamine hydrochloride, and the urethral pressure profile was reevaluated. Urethral pressure measurements obtained before surgery (3 dogs) and after phenylpropanolamine (6 dogs) were used to predict the likelihood of continence after surgery. Predicted outcomes included continence maintained without medication (3 dogs), continence maintained with phenylpropanolamine (2 dogs), and persistent incontinence despite phenylpropanolamine administration (4 dogs). After surgical repair of ectopic ureters, 2 of 9 (22%) dogs were continent without medication, and 2 (22%) maintained continence with phenylpropanolamine treatment. Various degrees of incontinence persisted in 5 of 9 (56%) dogs, 4 of which had urethral incompetence that had been documented as poorly responsive to phenylpropanolamine administration prior to surgery. Predicted outcomes were consistent with actual outcomes in 8 of 9 (89%) dogs, with predictions of incontinence proving accurate in 4 of 4 (100%) dogs and predictions of continence proving accurate in 4 of 5 (80%) dogs. Urodynamic assessment of dogs with ectopic ureters appears to be valuable for identifying concurrent functional abnormalities of the urinary bladder and urethra and for predicting postoperative outcome. PMID- 7775248 TI - An acute hemolytic transfusion reaction caused by dog erythrocyte antigen 1.1 incompatibility in a previously sensitized dog. AB - An acute hemolytic transfusion reaction resulting from dog erythrocyte antigen (DEA) 1.1 incompatibility developed in a dog previously sensitized to DEA 1.1 by a transfusion 3 years earlier. The dog developed fever, pigmenturia, and lethargy, and its PCV did not rise as expected. The donor blood was type DEA 1.1 positive, whereas the recipient's blood was type DEA 1.1, DEA 1.2, and DEA 7 negative. A major crossmatch was later found to be strongly incompatible. Studies of the recipient's plasma revealed a specific anti-DEA 1.1 alloantibody of the IgG class with high hemolysin and agglutinin activity. Such acute hemolytic transfusion reactions can be avoided by crossmatching previously transfused dogs and by using dogs that are type DEA 1.1 negative (and preferably also type DEA 1.2 and DEA 7 negative) as blood donors. PMID- 7775249 TI - Survival of a domestic cat with naturally acquired cytauxzoonosis. AB - A cat with acute onset of febrile systemic illness was determined to be infected with Cytauxzoon felis. The diagnosis was made on the basis of cytologic morphology of erythroparasites seen in blood smears and results of microfluorometric immunoassay for serum antibody directed against C felis parasitized RBC. Treatment consisted of parenteral administration of fluids and antibiotics. The cat recovered within 2 weeks. Circulating erythroparasites were not detected on blood smears from samples collected during follow-up examinations. However, high serum antibody titer persisted for at least 15 weeks after infection. The cat continued to be free of clinical disease 2.5 years after the initial diagnosis. Whether C felis infection persists in this cat has yet to be determined. This case indicates that some domestic cats can recover from naturally acquired cytauxzoonosis. PMID- 7775250 TI - Streptococcal fibrinous pericarditis and peritonitis in a Vietnamese pot-bellied pig. AB - An 8-month-old female Vietnamese pot-bellied pig was examined because of a 48 hour history of anorexia and signs of depression. Hypothermia, dehydration, pronounced respiratory effort, and muffled heart sounds were detected. Abdominal ultrasonography revealed ascites and hepatic congestion. Echocardiography revealed pericardial effusion and fibrinous pericarditis. Ultrasound-guided pericardiocentesis was diagnostic and therapeutic. Cytologic examination of pericardial and peritoneal fluid revealed degenerated neutrophils and intra-and extracellular gram-positive cocci. On microbial culture of pericardial and peritoneal fluid specimens, moderate growth of a beta-hemolytic Streptococcus sp of group G was observed. After initial treatment corrected hypothermia and dehydration, the pig was treated with sulfadiazine/sulfamerazine/sulfamethazine and oxytetracycline for 30 days. Echocardiographic examination 3 months after the initial examination revealed resolution of the pericardial effusion and fibrinous pericarditis. PMID- 7775251 TI - Factors affecting serum selenium and vitamin E concentrations in dairy cows. AB - Supplementation of selenium and vitamin E to enhance disease resistance in dairy cattle has become common, particularly to prevent periparturient reproductive disorders and mastitis. To establish reference values for serum vitamin E and selenium concentrations in postparturient dairy cattle and to determine whether serum concentrations of these micronutrients varied with season and stage of lactation, cows from a stratified random sample of 50 herds were studied for 1 year. Blood samples were collected from each of the 50 study herds twice, from the 10 most recently parturient cows or from 10% of the herd, whichever was greatest. Mean concentration of vitamin E and selenium was 2.55 micrograms/ml and 78.12 ng/ml, respectively. Vitamin E concentrations were significantly (P < 0.05) higher during the summer and fall than during the winter and spring. Selenium concentrations were significantly (P < 0.05) lower during the summer and fall than during the winter and spring. Herd, season of blood sample collection, and time since parturition were significant (P < 0.02) in explaining variation in vitamin E and selenium concentrations. PMID- 7775253 TI - In vitro cell monolayer invasion assay. PMID- 7775252 TI - Comparison of methods for measuring serum immunoglobulin concentrations in neonatal llamas. AB - Blood samples were collected from 25 neonatal llamas before suckling and at 24, 48, 72, 96, and 120 hours of age. Nine tests for determining serum immunoglobulin concentrations were performed on each sample, to compare within-test variation and correlations among tests. The single radial immunodiffusion assay was the only quantitative test and therefore, was judged the most accurate test for determining the status of passive transfer of immunoglobulins in neonatal llamas. Measurement of globulin concentration and total serum protein, and the sodium sulfite precipitation test were accurate when compared with radial immunodiffusion assay results. Measurements of total serum solids by use of a hand-held refractometer and of albumin concentration, and the zinc sulfate turbidity and 10% glutaraldehyde coagulation tests were not reliable for detecting failure of passive transfer in neonatal llamas. Ten of 25 neonatal llamas were suspected of having partial to complete failure of passive transfer on the basis of results of the single radial immunodiffusion assay. The other tests used in this study identified between 4 and 7 of these 10 llamas at 24 hours of age. On follow-up communication 4 to 6 months after the last-blood sample collection, none of the 25 llamas were identified as having been clinically ill or had received any treatments for illness associated with low immunoglobulin concentrations. PMID- 7775254 TI - Loss of heterozygosity on the short arm of chromosome 9 without p16 gene mutation in gastric carcinomas. AB - A putative tumor suppressor gene, p16 (MST1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4 inhibitor), was isolated and mapped on the short arm of chromosome 9 (9p). The significance of p16 mutations in gastric tumorigenesis was examined by assessing p16 mutations as well as loss of heterozygosity (LOH) on 9p in 13 gastric adenomas and 45 adenocarcinomas. LOH on 9p (IFNA; alpha-interferon locus) was detected in 22% (5/23 informative cases) of differentiated adenocarcinomas, 10% (1/10) of undifferentiated carcinomas and none (0/6) of the adenomas. Although we found a sequence polymorphism at the second position of codon 99 (CGC/CAC) of the p16 in one gastric adenoma patient, no somatic mutations were detected in any of the gastric adenomas or adenocarcinomas. These results suggest that p16 mutations probably do not contribute to gastric tumorigenesis. However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach. PMID- 7775255 TI - Frequent loss of the cyclin-dependent kinase-4 inhibitor gene in human gliomas. AB - Studies have shown that homozygous deletion of the cyclin-dependent kinase-4 inhibitor (CDK4I) gene, which is mapped to chromosome 9p21, is frequently observed in various types of human cancers. Here we report that the CDK4I gene was deleted in gliomas. Eight cell lines derived from glioblastomas and samples from 14 patients with various grades of gliomas were examined by Southern blot analysis. We found that the CDK4I gene was deleted in 7 of 8 (87.5%) cell lines and 7 of 9 (78%) samples from high-grade glioma patients, whereas it was deleted in 1 of 5 (20%) low-grade glioma samples. These results suggested that inactivation of the CDK4I gene may play an important role in the progression of human glioma. PMID- 7775256 TI - A radiation-induced murine ovarian granulosa cell tumor line: introduction of v ras gene potentiates a high metastatic ability. AB - A non-metastatic epithelial tumor cell line, OV3121, was established from ovarian granulosa cell tumor in B6C3F1 mouse irradiated with 60Co-gamma rays. OV3121 cells showed an epithelial morphology and grew in monolayer with a population doubling time of 28-30 h. The production of estradiol and the expression of cytokeratin confirmed the epithelial origin of the line. No pulmonary metastasis was observed from solid tumors after subcutaneous (s.c.) injection or after intravenous (i.v.) injection of a clonal subline, OV3121-1 cells. We examined the experimental metastasis of individual clones of OV3121-1 cells, containing various introduced viral oncogenes: v-Ha-ras, v-Ki-ras, v-fms, v-mos, v-raf, v src, v-sis, v-fos and v-myc. Among them, only OV3121-1 cells with v-Ha-MuSV or v Ki-MuSV produced lung colonies at high frequencies. In a more detailed analysis, the v-Ha-ras transfectants OV-ras4 and OV-ras7 were found to form colonies in various organs by metastasis from tumors after s.c. injection, as well as lung colonies after i.v. injection. Moderately metastatic OV-ras7 cells showed high gelatinolytic activity at 72 kDa (MMP-2) and 92 kDa (MMP-9) as compared with the parental OV3121-1 and OV-Neo control cells by zymographic analysis. However, more metastatic OV-ras4 cells produced progressively weaker bands of 72 kDa gelatinolytic activity. No gross alterations in the expression of MMP-1, MMP-3, TIMP-1 and TIMP-2 transcripts were detected in these cell lines. These results suggest that this ovarian granulosa cell tumor line may provide a useful system for understanding the mechanisms by which oncogenes influence the occurrence of metastasis. PMID- 7775257 TI - Frequent genetic instability in small intestinal carcinomas. AB - To determine whether genetic instability plays a part in the development of digestive tract carcinomas, we analyzed 3 microsatellite loci isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique was used to assess differences between tumor and matched normal DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of the 11 cases of small intestinal carcinoma (45%) had RERs, a significantly frequent finding. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas. PMID- 7775258 TI - Enzymatic basis for the accumulation of Lewis(b) antigen in uterine endometrial cancer. AB - In order to clarify the mechanism of the abnormal expression of Lewis(b) antigen, which was specific for uterine endometrial cancer tissue, the activities of alpha 1-->2fucosyltransferase, alpha 1-->3fucosyltransferase, and alpha 1- >4fucosyltransferase in normal endometrial tissues and uterine endometrial cancer tissues were determined. Further, an immunocytochemical study of the expression of blood group-related carbohydrate antigens in 6 cultured cell lines derived from various gynecologic malignant tumors was performed and the alpha 1- >2fucosyltransferase, alpha 1-->3fucosyltransferase, and alpha 1- >4fucosyltransferase activities of these cell lines were determined. Compared with normal endometrium, uterine endometrial cancer tissues showed significantly higher values of alpha 1-->2fucosyltransferase, alpha 1-->3fucosyltransferase, and alpha 1-->4fucosyltransferase activities. The specifically strong expression of type I carbohydrate chains, particularly the Lewis(b) antigen, was recognized in cultured cell lines derived from uterine endometrial cancer. Compared with those cell lines derived from uterine cervical cancer and ovarian cancer, the cultured cell lines derived from uterine endometrial cancer showed higher activities of alpha 1-->2fucosyltransferase and alpha 1-->4fucosyltransferase, which are enzymes related to the synthesis of Lewis(b) antigen. The cell lines derived from uterine endometrial cancer showed specifically high values of alpha 1-->4fucosyltransferase activity. These results suggest that the alpha 1- >2fucosyltransferase and alpha 1-->4fucosyltransferase activities, especially the alpha 1-->4fucosyltransferase activity, contribute to the abnormal expression of the Lewisb antigen in uterine endometrial cancer. PMID- 7775259 TI - Ubenimex activates the E-cadherin-mediated adhesion of a breast cancer cell line YMB-S. AB - It has been reported that ubenimex, a biological response modifier, has a direct anti-tumor effect. To clarify the mechanism involved, we examined the effects of ubenimex on the growth and adhesive property of a breast cancer cell line YMB-S. The cells proliferate in a floating manner without aggregation in normal complete medium. Ubenimex induced cell-cell and cell-surface adhesion of the cells accompanied with growth suppression. E-Cadherin localized at cell-cell contact sites of adhered cells, and anti-E-cadherin antibody inhibited the adhesion. Both Western blot analysis and binding assay disclosed that there was no apparent difference between E-cadherin levels of the cells before and after the treatment with ubenimex. These results indicate that ubenimex inhibits the proliferation of YMB-S cells and augments cell-to-cell adhesion through the induction of E cadherin-mediated adhesion resulting from the functional activation of pre expressed but inefficient E-cadherin. PMID- 7775261 TI - Reversal of tumor necrosis factor resistance in tumor cells by adriamycin via suppression of intracellular resistance factors. AB - Tumor necrosis factor (TNF) and various chemotherapeutic drugs show synergistic antitumor effects in vitro and in vivo, though the mechanism is not clear. Based on our previous finding that endogenous TNF (enTNF) acts as an intracellular resistance factor against exogenous TNF by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD), we examined the suppression of these resistance factors by chemotherapeutic drugs and the resulting increase in TNF cytotoxicity. Pretreatment of HeLa cells, which produce an appreciable amount of enTNF and show apparent TNF resistance, with TNF followed by adriamycin (ADM) resulted in an additive effect, whereas pretreatment with ADM followed by TNF resulted in a synergistic effect. After treatment of HeLa cells with ADM, the expression of enTNF was remarkably suppressed and MnSOD activity was decreased by one-half. These results indicate that suppression of the intracellular resistance factors, i.e., enTNF and MnSOD, by ADM plays an important role in the mechanism of the synergistic antitumor effect of TNF in combination with ADM. PMID- 7775262 TI - Pharmacokinetics of all-trans retinoic acid in pediatric patients with leukemia. AB - Since all-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), and its effectiveness appears to be related to the plasma or serum level, a pharmacokinetic study of ATRA was undertaken in nine patients with various leukemias. After oral administration at a dose of 30 mg/m2, the time required to reach the peak plasma level of ATRA (20-1198 ng/ml) was between 120 and 240 min and the apparent plasma elimination half life was 21-51 min. In addition, 13-cis retinoic acid was detected in the plasma of seven patients, indicating the occurrence of ATRA isomerization in vivo. ATRA therapy did not induce complete remission in all patients, even when high plasma levels were achieved. Among the six APL patients given ATRA therapy, one who failed to respond had a very low plasma ATRA level. These findings suggest that it may be useful to monitor plasma levels during oral ATRA therapy in order to achieve an appropriate treatment regimen. PMID- 7775260 TI - Do structural changes of T cell receptor complex occur in tumor-bearing state? AB - T cells in tumor-bearing mice and cancer patients were recently shown to be devoid of CD3-zeta chain, a signal-transducing invariant chain in T cell receptor (TCR) complex, and p56lck tyrosine kinase. In the present study, we investigated the structure and function of TCR complex in T cells from BALB/c mice bearing CSA1M fibrosarcoma. The expressions of TCR chains and p56lck in a T cell-enriched population from spleen were analyzed. Almost complete loss of CD3-zeta and p56lck was observed in the preparation from tumor-bearing mice as assessed by immunoblotting analysis using whole cell lysates, whereas the amounts of other TCR chains were relatively unchanged. However, these changes were due to the increase of contaminating Mac-1+ cells in the spleen of tumor-bearing mice because: 1) the removal of Mac-1+ cells led to the restoration of CD3-zeta and p56lck; and 2) CD3-zeta was clearly present when the preparation was solubilized with ionic detergent. Fc receptor gamma chain detected in the preparation from tumor-bearing mice disappeared along with the removal of Mac-1+ cells. These observations were further supported by the finding that addition of Mac-1+ cells from tumor-bearing mice to normal T cells resulted in loss of CD3-zeta, leaving CD3-epsilon largely intact. When T cells from tumor-bearing mice were highly purified by depletion of Mac-1+ cells, these T cells contained normal amounts of CD3-zeta at mRNA, protein, and surface levels, and expressed the properly assembled TCR complex on their cell surface. Moreover, stimulation of the TCR in these T cells by anti-TCR antibodies resulted in a comparable Ca2+ mobilization to that observed in normal T cells. These results suggest that no structural changes occur in TCR complex in our tumor-bearing mice, and that complete depletion of Mac-1+ cells in important to assess the structure of TCR complex. PMID- 7775264 TI - RS-22A, B and C: new macrolide antibiotics from Streptomyces violaceusniger. I. Taxonomy, fermentation, isolation and biological activities. AB - Three novel 36-membered macrolide antibiotics, RS-22A, B and C produced by Streptomyces violaceusniger have been isolated. These antibiotics were purified from an acetone extract of the mycelia followed by butanol extraction, centrifugal partition chromatography and HPLC. RS-22A, B, C showed antimicrobial activity against fungi and Gram-positive bacteria. PMID- 7775263 TI - Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin. AB - Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 60 mg/m2. The other 13 patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 80 mg/m2 with the granulocyte colony-stimulating factor support (2 micrograms/kg x 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m2 in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT 11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3 4 diarrhea than those with a lower SN-38 level (P = 0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea (P = 0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin. PMID- 7775265 TI - RS-22A, B and C: new macrolide antibiotics from Streptomyces violaceusniger. II. Physico-chemical properties and structure elucidation. AB - RS-22A, B and C are novel 36-membered macrolide antibiotics produced by Streptomyces violaceusniger. The structures of these antibiotics were unambiguously determined by 1D and 2D NMR and tandem-mass analysis of the oxidative derivative of RS-22C. PMID- 7775266 TI - 3'-Demethoxy-3'-hydroxystaurosporine, a novel staurosporine analogue produced by a blocked mutant. AB - 3'-Demethoxy-3'-hydroxystaurosporine, 1 (CGP 58,546), a novel staurosporine analogue, was isolated from a mutant of Streptomyces longisporoflavus R19 blocked in the last step of the biosynthetic pathway. CGP 58,546 was less potent than staurosporine, but it showed a more selective inhibition pattern against various subtypes of protein kinase C. PMID- 7775267 TI - A whole-cell Candida albicans assay for the detection of inhibitors towards fungal cell wall synthesis and assembly. AB - A whole-cell C. albicans screen was designed to identify novel inhibitors interacting with the synthesis, assembly and regulation of the fungal cell wall. C. albicans was grown in a paired broth assay in 96-well plates with natural product extracts or pure chemical compounds in the presence and absence of the osmotic stabilizer, sorbitol. Growth was visually examined over a 7-day period and scored into different growth categories. Positives from the sorbitol rescue were then examined under the microscope for morphological alterations and grouped into several morphological classes. Sorbitol protection and cell morphology were indicators of novel antifungal agents from natural product extracts and pure compounds. PMID- 7775268 TI - Novel squalestatins produced by biotransformation. AB - Microorganisms were screened for the ability to modify the squalene synthase inhibitor squalestatin 1. Biotransformation of 1 by two actinomycetes, S15106 and S15138, yielded three products hydroxylated on the 4,6-dimethyl-oct-2-enoyl side chain either at the 6 position (5) or 7 position (4 two diastereoisomers), and lacking the acetyl ester from the C-1 side chain. Many strains were found to hydrolyse the 4,6-dimethyl-oct-2-enoyl or acetyl esters to yield squalestatins 2 or 3. The 3-methyl ester (6) of 1 was obtained using Fusarium sp. F13945. This fungus also produced a farnesoic acid derivative, possibly in response to inhibition of its squalene synthase by 1. The biotransformation products of 1 all retained potent squalene synthase inhibitory activity. PMID- 7775269 TI - Action of cytogenin on lymphoid cells and their cytokine production. AB - Action of cytogenin on macrophages and T cells was investigated. Phagocytosis of yeast and production of PMA-elicited superoxide anion by macrophages taken from mice given cytogenin po were augmented. Cytogenin enhanced productions of IL-1 alpha by macrophages and IFN gamma and GM-CSF by spleen cells although it did not enhanced production of TNF alpha by macrophages and IL-6 by macrophages and spleen cells. Macrophages stimulated with cytogenin caused to stimulate proliferation of purified T cells in Intercell cultures in which each cell population was cultured without contact. Results suggest that cytogenin primarily activates macrophages to produce monokines such as IL-1 alpha and it causes to stimulate proliferation and differentiation of T cells resulting in production of lymphokines such as IFN gamma and GM-CSF. PMID- 7775270 TI - Modulation of macrophage activity in tumor bearing mice by cytogenin. AB - Cytogenin recovered the reduced mitogenic response to Con A of spleen cells of tumor bearing mice in vitro. The suppressive factor(s) was detected in adherent cell population in spleen cells. The reduced antitumor effector activity of spleen cells taken from tumor bearing mice was also augmented by the treatment with cytogenin in vitro. The effect of cytogenin was neutralized by the treatment with anti-Mac 1 serum. Administration of cytogenin inhibited the production of nitric oxide by macrophages which is known as one of suppressor factors. Results indicate that one possible action of cytogenin exhibiting antitumor activity in tumor bearing mice may be due to modulation of Mac 1 positive cells. PMID- 7775271 TI - Isolation and structural elucidation of antioxidative substances, carbazoquinocins A to F. PMID- 7775272 TI - Sch 50673 and Sch 50676, two novel antitumor fungal metabolites. PMID- 7775273 TI - GE20372 factor A and B. New HIV-1 protease inhibitors, produced by Streptomyces sp. ATCC 55925. PMID- 7775274 TI - Ochracenomicins A, B and C, new benz[a]anthraquinone antibiotics from Amicolatopsis sp. PMID- 7775275 TI - Isolation and identification of a new cephem compound from Penicillium chrysogenum strains expressing deacetoxycephalosporin C synthase activity. PMID- 7775276 TI - Synthesis and biological activity of derivatives of the herbicidal metabolite CL22T (phthoxazolin). PMID- 7775277 TI - The neuritogenesis inducer lactacystin arrests cell cycle at both G0/G1 and G2 phases in neuro 2a cells. PMID- 7775278 TI - Biosynthesis of armentomycin: a chlorinated nonprotein amino acid. PMID- 7775280 TI - Neural tuning characteristics of auditory primary afferents in the chicken embryo. AB - Primary afferent activity was recorded from the cochlear ganglion in chicken embryos (Gallus domesticus) at 19 days of incubation (E19). The ganglion was accessed via the recessus scala tympani and impaled with glass micropipettes. Frequency tuning curves were obtained using a computerized threshold tracking procedure. Tuning curves were evaluated to determine characteristics frequencies (CFs), CF thresholds, slopes of low and high frequency flanks, and tip sharpness (Q10dB). The majority of tuning curves exhibited the typical 'V' shape described for older birds and, on average, appeared relatively mature based on mean values for CF thresholds (59.6 +/- 20.3 dBSPL) and tip sharpness (Q10dB = 5.2 +/- 3). The mean slopes of low (61.9 +/- 37 dB/octave) and high (64.6 +/- 33 dB/octave) frequency flanks although comparable were somewhat less than those reported for 21-day-old chickens. Approximately 14% of the tuning curves displayed an unusual 'saw-tooth' pattern. CFs ranged from 188 to 1623 Hz. The highest CF was well below those reported for post-hatch birds. In addition, a broader range of Q10dB values (1.2 to 16.9) may related to a greater variability in embryonic tuning curves. Overall, these data suggest that an impressive functional maturity exists in the embryo at E19. The most significant sign of immaturity was the limited expression of high frequencies. It is argued that the limited high CF in part may be due to the developing middle ear transfer function and/or to a functionally immature cochlear base. PMID- 7775281 TI - The tonotopic map in the embryonic chicken cochlea. AB - The purpose of the present study was to determine the tonotopic map in the chicken cochlea at 19 days of incubation (E19) by obtaining characteristic frequencies (CFs) for primary afferents, labeling the characterized neurons, and documenting their projections to the papilla. The lowest and highest CFs recorded were 188 and 1623 Hz respectively. The embryonic tonotopic map coincided with maps reported for post-hatch chicks. There were no evidence that neurons selective to low frequencies project inappropriately to more basal locations of the embryonic papilla. Linear regression was used to estimate the frequency gradient (b = 0.037 +/- 0.012 In Hz/% [b +/- SEb]) and intercept (In C, where C = 111 Hz) of the semilog plot of frequency versus cochlear position (in % distance from apex). From these estimates the octave distribution was calculated to be 18.7%/octave or 0.58 mm/octave. These quantities were not significantly different from those found in post hatch chickens. We conclude that the tonotopic map of the avian cochlea for CFs between 100 and 1700 Hz is stable and relatively mature from age E19 to post-hatch day 21 (P21). The most striking sign of immaturity in the E19 embryo is the limited range of high CFs. We offer the hypothesis that, between the ages of E19 and P21, improvements in middle ear admittance alone or in combination with functional maturation of the cochlear base may be the principal factors responsible for the appearance of adult-like high CF limits and not an apically shifting tonotopic map. PMID- 7775279 TI - Effect of stress on cochlear glucocorticoid protein: acoustic stress. AB - Levels of glucocorticoid (GR) receptor protein were determined by a quantitative enzyme-linked immunosorbent assay (ELISA) technique in inner ear tissue of rats exposed daily to 85 dB SPL white noise for 4 hours on 3 consecutive days. GR levels in spiral ligament and organ of Corti tissues were detected using a monoclonal antibody to the GR receptor, BuGR2. A non-significant 13% decrease in GR levels of spiral ligament tissues was observed in the noise exposed animals relative to untreated animals. A statistically significant decrease of 27% in GR protein levels was seen in the organ of Corti region (P < 0.03), however. There was a concomitant increase of serum corticosterone levels (P < 0.03) in noise exposed animals as opposed to those of controls. These results indicate a tissue specific response of GR receptor to acoustic stress. Inner ear GR protein therefore may be a useful marker in determining the effect of stress on the inner ear. Finally, such data may be applicable to support the hypothesis that stress is an etiological agent in Meniere's disease. PMID- 7775282 TI - Salicylate-induced abnormal activity in the inferior colliculus of rats. AB - The evaluation of the spontaneous activity of 471 units from the external nucleus of the IC revealed that salicylate induces an increase of the spontaneous activity and the emergence of a bursting type of activity longer than 4 spikes. For sharply tuned units, the affected cells were from the frequency range of 10 16 kHz, which corresponds to the behaviorally measured pitch of salicylate induced tinnitus in rats. An exogenous calcium supplement, provided under the conditions shown to attenuate the behavioral manifestation of salicylate-induced tinnitus, abolished the modification of the spontaneous activity induced by salicylate. Finally, profound changes of activity were observed for cells not responding to contralateral sound. We propose that the observed long bursts of discharges represent tinnitus-related neuronal activity. The results are consistent with the hypothesis that GABA-mediated disinhibition is involved in the processing of tinnitus-related neuronal activity. PMID- 7775283 TI - Uptake of amikacin by hair cells of the guinea pig cochlea and vestibule and ototoxicity: comparison with gentamicin. AB - The distribution of amikacin (AK), an exclusive cochleo-toxic aminoglycosidic antibiotic (AA), and of gentamicin (GM), which is both cochleo- and vestibulo toxic, has been studied in cochlear and vestibular hair cells. Guinea pigs were treated during six days with one daily injection of AK (450 mg/kg/day) or GM (60 mg/kg/day). AAs were detected, using immunocytochemical technique with scanning laser confocal microscopy, in isolated cells from guinea pigs sacrificed from 2 to 30 days after the end of the treatments. Results demonstrate a rapid uptake (as soon as after 2-day treatment) of both AAs by cochlear and vestibular hair cells and a very slow clearance. Particularly GM and AK are detected in type I and type II hair cells of the utricles and cristae ampullaris. The presence of these two molecules with different toxic potentialities towards cochlear and vestibular hair cells indicates that the selective ototoxicity of aminoglycosides cannot be explained simply on the basis of particular uptake and accumulation in the different sensory hair cells. PMID- 7775284 TI - Shape and displacement patterns of the gerbil tympanic membrane in experimental otitis media with effusion. AB - This study assesses the visco-elastic properties of the tympanic membrane (TM) in isolated gerbilline temporal bones as a function of time after inducing experimental otitis media with effusion (OME). To do this we measured the TM displacements produced by application of sequences of static pressures across the TM, with a high resolution, real-time, differential moire interferometer, and the results were compared with measurements on healthy ears. Two methods of producing OME were used: in one group tubal plugging was performed to produce mild OME (the 'TP group'); in the other group electro-cauterization of the nasopharyngeal orifice of the Eustachian tube was used to cause a severe form of OME (the 'EC group'). The measurements were performed from one day up to ten weeks after surgery. In the TP group the displacement fringe patterns were normal, i.e. qualitatively they resembled the patterns of the control group. Quantitatively there was a significant decrease of displacement for a given pressure on the first day after surgery, followed by a trend of increase with time; after seven to ten days the displacement was larger than in the control group. In the EC group the displacement was significantly reduced after half a week, followed by a trend of increase with time, similar to what was found in the TP group; at one week the displacement was larger than in the control group, and at ten weeks the largest displacement was recorded. In the EC group the displacement patterns were often irregular; in some cases with changes suggesting the presence of weak spots in the TM where retraction pockets most likely could develop. OME seems to affect the stiffness of the TM promptly so that it is a potential parameter for early diagnosis. The stiffness changes may, if measurable in the clinical situation, become prognostic parameters in the treatment of OME. PMID- 7775285 TI - The effects of exposure to intense sound on the DC endocochlear potential in the chick. AB - Chicks were exposed to an intense pure tone (0.9 kHz, 120 dB SPL) for 48 h. The DC endocochlear potential was measured with a microelectrode inserted into scala media in six separate groups of animals between 0 and 12 days post exposure. Similar data were obtained from seven groups of unexposed control chicks between 2 and 15 days of age. One to nine animals were tested in each control or exposed group. The results in the control chicks revealed that the EP at 2 days of age (6.7 mV) was 36% of the mature value (15.2 mV) noted at 6 days of age. In the exposed animals, at 0-days recovery, the EP showed a 63% reduction relative to that measured in age matched control chicks. The level of EP in the exposed animals quickly recovered, and by 3 and 6 days post exposure exhibited a loss of only 7 and 3 percent relative to the age-matched controls. The recovery of EP was plotted against the recovery of evoked potential thresholds reported by others, and the time-course of the recovery functions were very similar. This relationship suggested that recovery of auditory function in the chick was highly correlated with the restoration of the EP. Damage to the tegmentum vasculosum and its capacity to secrete potassium, as well as the shunting of current through the damaged basilar papilla, are considered as mechanisms for the reduction of EP loss in the exposed ear. PMID- 7775286 TI - Three-channel Lissajous' trajectory of the binaural interaction components of human auditory middle-latency evoked potentials. AB - Three-channel Lissajous' trajectories (3-CLTs) of the binaural interaction component (BI) of auditory middle latency evoked potentials (AMLEPs) were derived from 14 normally hearing adults by subtracting the response to binaural clicks from the algebraic sum of monaural responses. AMLEPs were recorded in response to 65 dB nHL, rarefaction clicks, presented at a rate of 3.3/s. A normative set of BI 3-CLT measures was calculated and compared with the corresponding measures of simultaneously recorded, single-channel vertex-left mastoid and vertex-neck derivations of BI and of AMLEP to binaural stimulation (B). 3-CLT measures included: apex latency, amplitude and orientation, as well as planar segment duration, orientation, size and shape. The results showed seven main apices and associated planar segments ('Be', 'Bf', 'Bg', 'Bh', 'Bi1', 'Bi2' and 'Bj') in the 3-CLT of BI. Apex latencies of the BI 3-CLT were comparable to peak latencies of the vertex-left mastoid and vertex-neck AMLEP and BI records, both in their absolute values and in intersubject variability. Durations of BI planar segments were approximately 5.0 ms. Apex amplitudes of BI 3-CLT were larger than the respective peak amplitudes of the vertex-mastoid and vertex-neck BI records, while their intersubject variabilities were comparable. The lateralization of BI components may indicate asymmetric processing of binaural auditory input, or may be connected with anatomical asymmetry such as skull thickness. Preliminary analyses did not reveal a clear correlation between the lateralization of the BI component 'Bi2' and the handedness of the subject. We suggest that BI components of AMLEP may be associated with the primary auditory cortex and subcortical ascending structures. PMID- 7775287 TI - Possible origins of the non-monotonic intensity discrimination function in forward masking. AB - A non-monotonic intensity discrimination function in forward masking has been recently reported [Zeng et al. (1991) Hear. Res. 55, 223-230; Zeng and Turner (1992) J. Acoust Soc. Am. 92, 782-787] in which just-noticeable-differences (jnds) in intensity are largest for midlevel tones and smaller for soft and loud tones following an intense narrow-band noise. One hypothesis was that this midlevel hump reflects the contribution of low-spontaneous rate (SR) neurons to intensity coding, based on the differential recovery from forward masking of low SR and high-SR neurons [Relkin and Doucet (1991) Hear. Res. 55, 215-222]. The present study conducted three experiments stimulating different stages of the auditory system in an attempt to determine the peripheral and central origins of the midlevel hump. First, in two cochlear implant (CI) listeners, the forward masker produced a midlevel hump on the intensity discrimination function, suggesting that the synapses between the hair cell and the eighth nerve are probably not responsible for the hump, as they are bypassed and the eighth nerve is stimulated directly. Second, in auditory brainstem implant (ABI) listeners, the forward masker produced no midlevel hump, but the masked jnds were larger than those without a masker. The absence of the midlevel hump in the ABI listeners suggests that the occurrence of the hump requires physiological mechanisms in the auditory nerve transmission, or the intrinsic processing circuits of the cochlear nuclei, or both. Third, in normal-hearing listeners, an ipsilateral, 90 dB SPL, pure-tone forward masker produced a midlevel hump, which is similar to that using a narrow-band noise masker; whereas a contralateral forward masker produced essentially no midlevel hump, suggesting that binaural interactions at superior olivary complex and more central sites are probably not responsible. PMID- 7775288 TI - Nonlinear mechanics at the apex of the guinea-pig cochlea. AB - A heterodyne laser interferometer was used to observe the sound-evoked displacement patterns of Reissner's membrane and various other structures in the apical turn of the guinea-pig cochlea. Most structures (including the basilar membrane) were similarly tuned, and had best frequencies in the 200-350Hz range. A distinct notch was usually observed approximately 0.7 octaves above the best frequency, and amplitude- and phase-plateaus were observed at higher frequencies. In most other respects, however, the mechanical tuning resembled the frequency threshold curves of low frequency cochlear nerve fibers. In five reasonably intact, in vivo preparations, the frequency of the mechanical sensitivity notch was intensity-dependent: Compressive nonlinearities were observed above approximately 80 dB SPL on the low-frequency side of the notch, with antagonistically expansive nonlinearities on the high-frequency side. Two-tone suppression was observed in one of these preparations. Stimulus-related baseline position shifts were observed in another in vivo preparation. No such nonlinearities were observed in structurally damaged and/or > 1 hour post-mortem preparations. However, more robust nonlinearities were observed in all preparations at higher levels of stimulation (e.g. > 100-110 dB SPL). These high level nonlinearities diminished only slowly after death, and gave rise to various effects, including time-dependent (i.e. adapting) and severely distorted (e.g. peak-split and/or dc-shifted) responses. PMID- 7775289 TI - Processing of modulation frequency in the dorsal cochlear nucleus of the guinea pig: amplitude modulated tones. AB - The modulation frequency (Fm), particularly high Fm (> 200 Hz), in amplitude modulated (AM) tones can elicit the perception of the periodicity pitch (Langner, 1992). In this study, single unit responses to the Fms of the sinusoidal AM tones were investigated at 50 to 90 dB SPL. The recordings were made from the dorsal cochlear nucleus (DCN) of neuroleptic anesthetized guinea pigs with an intact cerebellum. The DCN units show a good capability of phase-locking to Fm at 400 1200 Hz. On-S-type II and Pauser/Buildup (P/B) units have a high modulation gain (7.2-8.3 dB). P/B units can preserve the high modulation gain (5-9 dB) up to 90 dB SPL. The modulation gain exponentially increases with decreasing modulation depth (Dm) and the phase-locking is detectable even at the Dm as low as 2-5%. The 'central skipping' of the phase-locking peak has been found at deep Dms in a few cases. The synchronization is independent of the discharge rate and can remain high even when the responses to AM tones are inhibited below the spontaneous activity. Such encoding behaviors over the unit's response area show that the Fm phase-locking is strong near or at its characteristic frequency (CF). The synchronization index (SI) versus carrier frequency (Fc) curve is similar to the inverse shape of tuning curve but more narrowly tuned than the iso-intensity function of pure tones at moderate to high intensity levels. The phase-locking is related to the unit's spontaneous rate (SR). The average modulation gain of the lower SR (< or = 2 spikes/s) units is 5 dB higher than that of the higher SR (> 2 spikes/s) units (8.16 and 2.92 dB, respectively) at 70 dB SPL. These results suggest that AM information is temporally encoded over broad ranges of modulation parameters in the DCN and is conveyed by the Fc channel. Such a timing mechanism can play an important role in processing of complex sounds under normal acoustic conditions. PMID- 7775290 TI - The auditory neurobiology of marsupials: a review. AB - The marsupials, the large group of mammals which develop during fetal life in an externalized pouch, have been given little attention by auditory neurobiologists. In this review the structure of the auditory systems of the handful of marsupials which have been studied is described, the course of auditory development mapped, and the behavioral and electrophysiological manifestations of hearing examined. It is argued that research on the highly accessible developing marsupial will provide information about the development of hearing difficult to obtain from, but applicable to all, mammalian species. PMID- 7775291 TI - Regenerated hair cells in the European starling: are they more resistant to kanamycin ototoxicity than original hair cells? AB - Previous work from our laboratory [Marean et al. (1993) Hear. Res. 71, 125-136] has shown that a 10 day dose of 200 mg/kg/day kanamycin produced damage to the basal 34% of the starling basilar papilla. We also observed that repeating the dosing schedule following a 4 month survival period resulted in significantly less damage to the regenerated auditory epithelium. The present study investigated whether or not this apparent resistance was the result of a tendency for regenerated hair cells to be less susceptible to kanamycin ototoxicity, or if other, systemic factors may be involved. Eight European starlings were given subcutaneous injections of 200 mg/kg/day kanamycin for 10 days. Serum levels of kanamycin were measured at the time of sacrifice for all birds, and the basilar papillae of all birds were examined by scanning electron microscopy (SEM). Two of these birds (Group 1) were sacrificed immediately following the dosing period. Two of the birds were allowed to survive for 60 days (Group 2). Two of the birds were redosed with 200 mg/kg/day for 10 days after 60 days survival (Group 3). Finally, two birds were redosed with 250 mg/kg/day until serum levels of kanamycin were the same as Group 1 when sacrificed (> 9 micrograms/ml). The SEM results showed that the regenerated auditory epithelium of the birds dosed a second time sustained less damage compared to previously untreated ears, even though the dosing regimen was the same (Group 3 versus Group 1). The regenerated auditory epithelium of birds dosed a second time sustained the same damage as previously untreated animals when the dosage was increased to attain similar serum levels (Group 4 versus Group 1). These results suggest metabolic changes occur in the starling in response to the initial dose of kanamycin which do not necessarily involve changes in hair cell resistance to ototoxicity. PMID- 7775292 TI - Estimation of the pulmonary capillary transport function in isolated rabbit lungs. AB - Recently, we presented a method for estimating the pulmonary capillary volume and transport function based on the use of a reference indicator and two or more indicators that rapidly equilibrate (radially) with the tissue (i.e., the concentrations in the vascular and extravascular spaces at a given axial location are in equilibrium) during transit through the capillaries in a bolus-injection indicator dilution method (S. H. Audi, G. S. Krenz, J. H. Linehan, D. A. Rickaby, and C. A. Dawson. J. Appl. Physiol. 77:332-351, 1994). The objectives of the present study were 1) to determine whether [14C]diazepam and [3H]alfentanil equilibrate sufficiently rapidly between the vascular space and tissue and with sufficiently different pulmonary extra-vascular mean residence times to be used in a single bolus to estimate the pulmonary capillary volume and transport function using this method and 2) to estimate the pulmonary capillary volume and transit time distribution in isolated perfused rabbit lungs. Both [14C]diazepam and [3H]alfentanil were found to be rapidly equilibrating indicators by the criteria that, over a wide range of flow rates, their respective venous effluent concentration curves were nearly congruent on a time scale normalized to the lung mean transit time for the reference indicator (fluorescein isothiocyanate dextran). In addition, at a given plasma albumin concentration, [14C]diazepam had a significantly longer extravascular mean residence time than [3H]alfentanil, e.g., at 6% plasma albumin concentration, the extravascular mean residence time of [14C]diazepam was more than twice that of [3H]alfentanil. On average, the estimated pulmonary capillary volume for a 2.7-kg was approximately 4.2 ml or approximately 44% of the total pulmonary vascular volume (9.5 ml). The relative dispersion of the pulmonary capillary transport function of the rabbit was approximately 90%. PMID- 7775293 TI - Ozone-induced airway hyperresponsiveness: role of superoxide anions, NEP, and BK receptors. AB - We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18-24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded. PMID- 7775294 TI - Catecholaminergic effects of prolonged head-down bed rest. AB - Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1-4, 4-24, 144-168 (day 7), and 312-336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights. PMID- 7775295 TI - Diaphragm thickness heterogeneity at functional residual capacity and total lung capacity. AB - One of the determinants of muscular force is the number of myofibrils in parallel, which is approximated by thickness. To better understand the heterogeneity of diaphragm thickness, we quantified the interregional and radial patterns of thickness of nine canine diaphragms rapidly perfusion fixed in situ with glutaraldehyde at functional residual capacity (FRC) (n = 6) and total lung capacity (TLC) (n = 3). Thickness was determined gravimetrically from punch biopsies radiating from the central tendon to rib cage insertion in ventral, middle, and dorsal costal and crural regions. For comparison, the contralateral unfixed hemidiaphragm was sampled in the same fashion. The findings of this investigation include the following. 1) The costal diaphragm exhibits the same pattern of interregional heterogeneity at FRC, TLC, and in the freshly excised state. 2) The costal diaphragm is significantly thinner at FRC in situ (0.17 +/- 0.01 cm) than is the freshly excised contralateral diaphragm (0.21 +/- 0.01 cm; P < 0.05), whereas there is no significant difference between thickness at TLC and the freshly excised state. 3) There is significant, previously underscribed, radial tapering from the rib cage attachment (0.24 +/- 0.02) to the central tendon insertion (0.15 +/- 0.01 cm; P < 0.05) that is exaggerated at TLC. 4) With passive inflation from FRC to TLC, the greatest increase in thickness occurs close to the rib cage attachment for the ventral and medial costal regions but close to the central tendon in the dorsal and crural regions. We conclude that the diaphragm at FRC and TLC exhibits radial thickness heterogeneity that cannot be predicted from dimensions of the freshly excised diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775296 TI - Fluid changes during pregnancy: use of bioimpedance spectroscopy. AB - The increase in body water during pregnancy is responsible for the largest portion of weight gain and is of interest of clinical practitioners. However, assessing changes in body fluids is not easily accomplished during pregnancy. The purpose of this study was to examine the accuracy of bioelectrical impedance spectroscopy for estimating fluid volumes before, during, and after pregnancy. Ten healthy adult women were recruited for the study. Total body water (TBW) and extracellular fluid (ECF) volume were measured at baseline (preconception); 8-10, 24-26, and 34-36 wk of gestation; and 4-6 wk postpartum by deuterium oxide and NaBr dilution, respectively. Estimates of TBW and ECF were also obtained by bioimpedance spectroscopy (BIS). At baseline, mean values for dilution and BIS estimates of TBW and ECF were 33.2 +/- 4.6 (SD) vs. 31.6 +/- 6.2 liters and 15.2 +/- 1.3 vs. 16.9 +/- 2.3 liters, respectively. TBW and ECF estimated by BIS were not significantly different from the dilution values at any time point. These results suggest that BIS may be useful in estimating volumes of ECF and TBW during pregnancy. PMID- 7775297 TI - Hyperpnea with dry air causes time-dependent alterations in mucosal morphology and bronchovascular permeability. AB - This study examines the morphological and physiological changes that occur in canine peripheral airways after hyperpnea with dry air. Peripheral airways were exposed to a 5-min 2,000 ml/min dry air challenge (DAC) at 24, 6, 2, or 1 h before or 60 s after (0 h) the injection of colloidal carbon. After recording the dry air-induced increase in peripheral airway resistance, the lungs were removed and prepared for morphometric analysis (n = 5). Light microscopy revealed that 50% of the airway perimeter appeared damaged at 0, 1, and 2 h after DAC, and repair was evident 6-24 h after the challenge. The average goblet-to-ciliated cell ratio decreased from 0.34 before DAC to 0.15 after DAC and recovered within 24 h. Dry air-induced bronchovascular leakage occurred immediately after DAC and persisted for > or = 24 h. DAC decreased mast cell number only in regions where the mucosa was damaged, and this decrease was inversely correlated with bronchovascular leakage. Finally, leukocyte infiltration was evident 1-2 h after DAC and continued throughout the 24-h period. We conclude that hyperpnea with dry air causes mucosal injury, inflammation, and microvascular leakage and that these dry air-induced effects persist for > or = 24 h after DAC. PMID- 7775298 TI - Estimation of dynamic chemoresponsiveness in wakefulness and non-rapid-eye movement sleep. AB - We developed a method for quantifying dynamic chemoresponsiveness on the basis of the ventilatory response to pseudorandom binary CO2 stimulation. The dynamic chemoreflex gain (GD) and effective time delay (TDeff) relating breath-to-breath fluctuations in alveolar PCO2 to ventilation were evaluated at frequencies between 0 and 0.05 Hz. Application of the method to simulated "data" showed that estimation errors in GD and TDeff were most likely to be minimized in the range of 0.01-0.03 Hz, corresponding to periodicities of 30-100 s. Estimation of TDeff was generally more susceptible to error than that of GD because of the limited time resolution of the breath-by-breath measurements. In eight awake normal adults, we compared estimates of GD derived from the pseudorandom binary CO2 stimulation test with peripheral and central hypercapnic sensitivities deduced from single-breath and Read rebreathing measurements in the same subject. GD at 0.02 Hz was highly correlated with peripheral hypercapnic sensitivity but poorly correlated with central hypercapnic sensitivity, underscoring the importance of the peripheral chemoreflexes in mediating ventilatory responses to phasic stimuli. Application of the procedure to a different group of 10 healthy volunteers during wakefulness and stage 2 sleep showed decreases in GD in 8 subjects but increases in 2 subjects. However, for the group as a whole, GD and TDeff did not change significantly between wakefulness and sleep. The proposed method may provide information more pertinent to periodic breathing than traditional CO2 response tests do, since the chemoreflex responses to phasic variations in blood gases are likely to be important in determining ventilatory control during sleep. PMID- 7775299 TI - Alterations in intramuscular connective tissue after limb casting affect contraction-induced muscle injury. AB - This study examined the effect of alterations in rat intramuscular connective tissue (CT), secondary to limb immobilization, on the muscle's susceptibility to contraction-induced injury. Hindlimbs were casted for 3 wk with the extensor digitorum longus muscle fixed in a shortened (IM-SP) or lengthened position (IM LP). An age-matched control group remained uncasted. Extensor digitorum longus muscles were injured in vivo by using a motorized foot pedal that repeatedly flexed and extended the foot while the muscle was electrically stimulated during plantar flexion. Four hours postinjury, maximum isometric tetanic force (Po) was measured in vitro and was used as a functional index of muscle injury. Muscles were fixed, sectioned, and stained for later analysis. Intramuscular CT concentration, expressed as the ratio of CT area to muscle fiber area, was significantly higher in both IM-SP (0.153 +/- 0.003) and IM-LP (0.174 +/- 0.003) groups compared with controls (0.104 +/- 0.003). Po values of injured muscles both IM-LP and IM-SP were higher than the injured controls' Po of 9.41 +/- 0.63 N/cm2 (P < 0.05). Injured IM-LP muscle forces were significantly higher than those of IM-SP. This study demonstrated that limb immobilization increases intramuscular CT concentration, which is accompanied by attenuation of muscle injury. We conclude that remodeling of intramuscular CT affects the muscle's resistance to contraction-induced injury. PMID- 7775300 TI - Visualization of airway obstruction in vivo during pulmonary vascular engorgement and edema. AB - Although pulmonary vascular engorgement has often been hypothesized to decrease airway caliber, leading to airway obstruction in asthma, direct evidence for this hypothesis is lacking. In the present study, we used high-resolution computed tomography to directly measure the changes in the caliber and wall thickness of conducting airways after volume loading with normal saline (NS) and homologous blood. Five anesthetized dogs received 0.2 mg/kg of atropine followed by either three sequential fluid challenges of 50 ml/kg of NS or two sequential challenges of 25 ml/kg of blood. Several weeks later, the same dogs received the other fluid challenge. Volume loading with 150 ml/kg of NS decreased the average airway luminal area to 68 +/- 3% (+/- SE) of baseline. Concomitantly, airway wall thickness increased to 150 +/- 6% of baseline. Volume loading with 50 ml/kg of blood decreased the average airway luminal area to 81 +/- 2% of baseline. Concomitantly, airway wall thickness increased to 108 +/- 2% of baseline. Therefore, for comparable changes in pulmonary vascular pressure, an infusion of NS caused a significantly greater decrease in airway luminal area and a larger increase in airway wall thickness than an infusion of blood. This suggests that the presence of edema fluid in or immediately surrounding the airway wall acts to decrease the airway lumen. However, since the degree of airway narrowing was only moderate, even with a most extreme fluid load, it seems unlikely that airway wall thickening or edema could be a primary cause of conducting airway obstruction in patients with asthma or impaired left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775301 TI - Exercise training alters the Ca2+ and contractile responses of coronary arteries to endothelin. AB - We tested the hypothesis that alterations in myoplasmic free Ca2+ (Ca(m)) regulation in coronary smooth muscle after exercise training (Ex) underlie changes in vasomotor function. Yucatan miniature pigs were endurance trained by treadmill running for 16-20 wk. Simultaneous determination of Ca(m) (fura-2 microfluorometry) and contraction during endothelin exposure in coronary arteries were then performed. Endothelin (10(-9) to 10(-7) M) was administered either cumulatively or as a single concentration. Ex significantly attenuated the Ca(m) response to 10(-9) and 10(-8) M endothelin. Developed tension was significantly diminished at 10(-8) M endothelin in Ex pigs, producing a rightward shift in the concentration-developed tension response. Attenuated Ca(m) and contractile response to 10(-8) M endothelin were present after Ex whether endothelin was applied cumulatively or as a single concentration. The developed tension-Ca(m) relationship showed an increased Ca(m) sensitivity of contraction with Ex. Endothelin (10(-8) M)-induced Ca2+ influx, estimated by Ba2+ influx in low-Na+ solution, was increased threefold in coronary arteries from Ex pigs. The decreased Ca(m) in the presence of increased divalent cation (i.e., Ca2+) influx during 10(-8) M endothelin suggests a greatly enhanced sarcolemmal Ca2+ cycling in coronary arteries from Ex pigs. PMID- 7775302 TI - Chamber for controlling end-tidal gas tensions over sustained periods in humans. AB - Although techniques for the short-term control of end-tidal gases exist, the lack of a satisfactory technique for longer-term control of the end-tidal gases has limited protracted physiological experiments of this nature. We have constructed a chamber in which subjects can be comfortable for many hours while having their end-tidal gas composition monitored and controlled. The system for controlling the end-tidal gas composition is based on a principle described by Swanson and Bellville (J. Appl. Physiol. 39: 377-385, 1975) in which end-tidal PO2 (PETO2) and PCO2 (PETCO2) are monitored and deviations of the actual PETO2 and PETCO2 (PETCO2) are monitored and deviations of the actual PETO2 and PETCO2 from the desired values are corrected by a feedback mechanism that adjusts the inspired gas composition accordingly. End-tidal and inspired gas tensions are measured via a nasal catheter connected to a mass spectrometer. A computer averages the end tidal and inspired gas tensions and, at 5-min intervals, adjusts the gas composition inside the chamber. During 8 h of isocapnic hypoxia, the system held the 5-min average value for PETO2 within 2 Torr of the desired value (55 Torr) and the value for PETCO2 within 0.35 Torr of the desired value (the resting value for each subject) in four subjects. PMID- 7775303 TI - Ventilatory response to 8 h of isocapnic and poikilocapnic hypoxia in humans. AB - Almost all studies of the effects of prolonged hypoxia on ventilation (VE) in humans have been performed with the end-tidal PCO2 (PETCO2) left uncontrolled. The purpose of this study was to compare the effects of 8 h of hypoxia with PETCO2 held constant with 8 h of hypoxia with PETCO2 left uncontrolled. Ten subjects completed the study. Each was seated inside a chamber in which the inspired gas could be controlled so as to maintain the desired partial pressures of end-tidal gases (sampled via nasal catheter) constant (see L.S.G.E. Howard et al. J. Appl. Physiol. 78:1088-1091, 1995.). Three 8-h protocols were employed: 1) isocapnic hypoxia, at an end-tidal PO2 of 55 Torr with PETCO2 held at the subject's resting value; 2) poikilocapnic hypoxia, at the same end-tidal PO2; and 3) control, where the inspired gas was air. VE was measured (over 3 min) at 0 and 20 min and at hourly intervals between 1.5 and 7.5 h. There was a rise in VE during isocapnic hypoxia [from an initial VE of 16.2 +/- 1.3 (SE) l/min to a final VE of 24.8 +/- 1.6 l/min], which was significant compared with poikilocapnic hypoxia and control values (P < 0.001, analysis of variance). There was no significant progressive rise in VE during poikilocapnic hypoxia compared with control values. These results show that isocapnic hypoxia produces a progressive increase in VE when sustained over an 8-h period. The onset of this response is faster than has been noted in studies of the progressive rise in VE associated with the poikilocapnic hypoxia of altitude. PMID- 7775304 TI - Alterations in respiratory control during 8 h of isocapnic and poikilocapnic hypoxia in humans. AB - In the preceding companion paper (L. S. G. E. Howard and P.A. Robbins, J. Appl. Physiol. 78: 1092-1097, 1995), we showed that ventilation rises during 8 h of isocapnic hypoxia. In the present study we report the changes that occur in the ventilatory response to acute hypoxia (AHVR) over 8 h of both isocapnic and poikilocapnic hypoxia. Ten subjects completed the study. Each was seated inside a chamber in which the inspired gas could be controlled so as to maintain the desired end-tidal gases (sampled via nasal catheter) constant. Three 8-h protocols were compared: 1) isocapnic hypoxia, at an end-tidal PO2 of 55 Torr with the end-tidal PCO2 held at the subject's resting value; 2) poikilocapnic hypoxia, at the same end-tidal PO2; and 3) control, where the inspired gas was air. AHVR was measured before and at 20 min and 4 and 8 h after the start of the experiment. A sequence of hypoxic square waves and sawtooth inputs was imposed by an end-tidal forcing system, with the subject breathing through a mouthpiece. End tidal PCO2 was held constant at 1-1.5 Torr above resting. Values for hypoxic sensitivity (Gp; 1.min-1.%-1) and hypoxia-independent ventilation (Vc; l/min) were calculated for each test of AHVR. Both Gp and Vc increased significantly during both hypoxic exposures in relation to control (P < 0.001, analysis of variance). Over the 8-h period, increases in Gp were 87% in isocapnic hypoxia and 44% in poikilocapnic hypoxia, and increases in Vc were 89% in isocapnic hypoxia and 84% in poikilocapnic hypoxia. There were no significant differences between the isocapnic and poikilocapnic exposures. We conclude that Gp and Vc rise mainly as result of hypoxia per se and not the associated alkalosis. PMID- 7775305 TI - Ozone toxicity in the rat. I. Effect of changes in ambient temperature on extrapulmonary physiological parameters. AB - These studies examined the effects of exposure to near environmental levels of ozone (O3) on the unanesthetized unrestrained rat as well as the influence of changes in ambient temperature (Ta) on the observed responses. Male Fischer 344 rats were implanted with radiotelemetry transmitters that permitted continuous monitoring of electrocardiogram, heart rate, core body temperature (Tco), and activity. Telemetry animals (n = 4-5/group) were combined with nontelemetry animals to produce nine treatment groups (n = 44-50/group) composed of combinations of one of three O3 exposure regimens (0.0 ppm x 24 h/day, 0.5 ppm x 6 h/day, or 0.5 ppm x 23 h/day) paired with one of three Ta levels (10, 22, or 34 degrees C). The experimental protocol consisted of a Control Period (filtered air; 1 day), Treatment Period (O3; 5 days), and Recovery Period (filtered air; 7 days). At specific intervals during the experiment, subgroups (n = 6) of nontelemetry animals were randomly selected from each treatment group, anesthetized with urethan, and intubated, and their lungs were lavaged with warm saline. In general, results from the bronchoalveolar lavage procedure indicated that toxicity increased in magnitude and duration as the length of time of O3 exposure increased and the Ta decreased. Similarly, whereas minimal extrapulmonary effects were observed at an Ta of 34 degrees C, O3 exposures at Ta levels of 22 and 10 degrees C produced significant decreases in heart rate (160 and 210 beats/min, respectively), Tco (2.0 and 3.5 degrees C, respectively), and body weight (15 and 40 g, respectively). Decreases in these functional parameters reached their maxima over the first 2 exposure days and returned to control levels after the 3rd day of exposure. These data demonstrate the profound impact of Ta on Tco and other extrapulmonary parameters in the conscious unrestrained rat exposed to O3. Furthermore, these results suggest an integral role for both Tco and Ta in determination of the uptake of inhaled pollutants and modulation of the subsequent toxic effects and may have important implications with respect to the assessment of toxic risk. PMID- 7775306 TI - Acute lung injury in endotoxemic pigs: role of leukotriene B4. AB - The role of leukotriene B4 (LTB4) in the pathogenesis of acute lung injury was examined in endotoxemic pigs. In a preliminary study, the activity and specificity of an LTB4-receptor antagonist, LY-306669, were evaluated. In vitro, LY-306669 completely blocked the functional upregulation of phagocyte opsonin receptors induced by LTB4 but had a much smaller effect on opsonin receptor upregulation induced by platelet-activating factor. In pigs treatment with LY 306669 prevented leukopenia induced by injection of authentic LTB4 but had no effect on the hematologic or hemodynamic effects of PAF or U-48816, a thromboxane A2 mimetic. In a second study, pigs received an intravenous priming dose of lipopolysaccharide (LPS) at time (t) = -18 h and were randomized to receive 1) no further treatment (n = 5), 2) LPS (250 micrograms/kg over 1 h beginning at t = 0 h) and LY-306669 (10 mg/kg bolus and 3 mg.kg-1.h-1 infusion beginning at t = -15 min) (n = 7), or 3) LPS and vehicle (n = 6). Treatment with LY-306669 significantly ameliorated LPS-induced hypoxemia, pulmonary edema, and alveolitis. These data suggest that LTB4 is an important mediator of pulmonary dysfunction and transendothelial migration of neutrophils in LPS-induced acute lung injury. PMID- 7775307 TI - Structure of the latissimus dorsi muscle and respiratory function. AB - The aim of this study was to evaluate whether respiratory function influences the structure of the latissimus dorsi muscle (LD). Twelve patients (58 +/- 10 yr) undergoing thoracotomy were studied. Lung and respiratory muscle function were evaluated before surgery. Patients showed a forced expired volume in 1 s (FEV1) of 67 +/- 16% of the reference value, an FEV1-forced vital capacity ratio of 69 +/- 9%, a maximal inspiratory pressure of 101 +/- 21% of the reference value, and a tension-time index of the diaphragm (TTdi) of 0.04 +/- 0.02. When patients were exposed to 8% CO2 breathing, TTdi increased to 0.06 +/- 0.03 (P < 0.05). The structural analysis of LD showed that 51 +/- 5% of the fibers were type I. The diameter was 56 +/- 9 microns for type I fibers and 61 +/- 9 microns for type II fibers, whereas the hypertrophy factor was 87 +/- 94 and 172 +/- 208 for type I and II fibers, respectively. Interestingly, the histogram distribution of the LD fibers was unimodal in two of the three individuals with normal lung function and bimodal (additional mode of hypertrophic fibers) in seven of the nine patients with chronic obstructive pulmonary disease. An inverse relationship was found between the %FEV1-forced vital capacity ratio and both the diameter of the fibers (type I: r = -0.773, P < 0.005; type II: r = -0.590, P < 0.05) and the hypertrophy factors (type I: r = -0.647, P < 0.05; type II: r = -0.575, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775308 TI - Complement activation in divers after repeated air/heliox dives and its possible relevance to DCS. AB - Plasma levels of the anaphylatoxin C5a were measured in 19 divers performing repeated air dives. Blood samples were collected immediately before the first dive and 2 h after the first and the second or third dive. Serum obtained at the same times was subjected to complement activation in vitro by air bubbles. Six divers developed symptoms of decompression sickness (DCS). Most intravascular bubbles were observed in divers with the lowest plasma levels of C5a. Postdive plasma levels of C5a did not increase compared with predive levels, nor were postdive levels significantly different after two or three dives compared with the first dive. Repeated dives did not influence the amounts of C5a generated in vitro. Neither plasma levels of C5a nor C5a generated in vitro were significantly different in divers who experienced symptoms of DCS vs. divers without symptoms of DCS. We conclude that plasma level of C5a and measurement of C5a generation in vitro cannot be used to predict DCS. PMID- 7775309 TI - Pulmonary venous congestion augments respiratory motoneuronal responses to cigarette smoke in rabbit. AB - We examined the effects of cigarette smoke inhaled during subthreshold pulmonary venous congestion (sPVC) on phrenic nerve (PN) and unit activity in the ventral respiratory group in rabbits. sPVC was achieved by inflating a balloon in the left atrium. Inhalation of low-nicotine cigarette smoke produced initial prolonged bursts in 34 (19 bulbospinal) out of 43 inspiratory (I) cells and in PN. Smoke decreased the activity of 29 out of 36 expiratory (E) cells (27 of 32 early E and 2 of 4 late E). The prolonged PN bursts occasionally progressed to doublets superimposed over regularly occurring PN bursts. sPVC augmented the smoke effects: I cells displayed greater increases in spikes/burst (27 vs. 12%; P = 0.02) and burst duration (42 vs. 20%; P = 0.02) and greater decreases in interburst interval (34 vs. 10%; P < 0.02); PN displayed greater increases in I time (40 vs. 27%; P < 0.05), greater decreases in E time (18 vs. 26%; P < 0.05), and a greater incidence and duration of time of PN doublets (29 +/- 9 vs. 9 +/- 4 s; P < 0.03); E cells displayed greater decreases in spikes/burst (43 vs. 29%; P = 0.01) and burst durations (35 vs. 18%; P < 0.01). Smoke-induced respiratory changes may be exaggerated during sPVC. PMID- 7775310 TI - In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. I. Theory and error analysis. AB - We developed a procedure for measuring pulmonary angiotensin-converting enzyme kinetics with fluorine-18 fluorocaptopril and positron emission tomography (PET). The method is based on the application of a compartmental receptor model that represents the kinetics of two species of ligand, presumably the trans and cis conformers of captopril. The input function was characterized and includes corrections for the labeled metabolites of fluorocaptopril. Application of the procedure to lung time-activity data obtained with PET produced estimates of kinetic parameters demonstrating fast kinetics for one conformer and slower kinetics for the other. Simulation studies were performed to evaluate the sensitivity of the estimated parameters to errors in the model assumptions and in measured values for variables required for analysis of the PET data. Estimates for two of the kinetic parameters, the amount of perfused unbound functional enzyme normalized to regional lung volume and the association rate constant for the trans conformer, were relatively stable even with large errors in the input data, varying < 30% from true values for all perturbations. Thus, the procedure produces reliable estimates of the kinetics of the trans conformer of captopril as well as theoretical curves that are close to the observed data. PMID- 7775311 TI - In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. II. Implementation and application. AB - We measured pulmonary angiotensin-converting enzyme (ACE) kinetics with fluorine 18 captopril and positron emission tomographic (PET) imaging in five control dogs and in five dogs after 20-30 min of left caudal lobe (LCL) hypoxic ventilation. Time-activity data obtained with PET were interpreted with a compartmental receptor model relating changes in tissue and blood activity to one another within the region. In control dogs, the mean ratio of regional blood flow (measured by PET) between left and right dorsal lung regions was 0.90 +/- 0.16 (SD) vs. 0.54 +/- 0.24 (P < 0.05) in LCL hypoxic dogs. In control dogs, the amount of perfused unbound enzyme normalized to regional extravascular water concentration (Bmax/EVLW) averaged 13.3 +/- 8.9 x 10(-6) mmol ACE/ml EVLW; the ratio of regional values between the left and right sides was 1.02 +/- 0.18. In the LCL hypoxic dogs, Bmax/EVLW was 9.7 +/- 11.3 x 10(-6) mmol/ml hypoxic lung region and the ratio was 0.47 +/- 0.31 (P < 0.05). In control dogs, the coefficient of variation for Bmax/EVLW among regions was only 19 +/- 10%, although the between-dog variation was greater (64 +/- 4%). We conclude that this completely noninvasive method appears to be a promising approach for evaluating the expression of pulmonary ACE in vivo. PMID- 7775312 TI - Effects of high pressures of various gas mixtures on rat striatal dopamine detected in vivo by voltammetry. AB - This work was performed to study the effect of pressure of various gas breathing mixtures on dopaminergic activity in the striatum by in vivo differential pulse voltammetry using carbon multifiber electrodes chronically implanted in 23 freely moving rats. Compression (0.5 bar/min) in a helium-oxygen mixture induced an increase in striatal extracellular dopamine (DA) beginning at 10-20 bars and reaching 32% above precompression levels when arriving at 90 bars (n = 9). To demonstrate that this increase is dopaminergic, nine rats with right nigrostriatal pathway 6-hydroxydopamine lesions were compressed in the same conditions. In this case, the increase in DA did not occur in the right caudate nucleus but was recorded in the intact left caudate nucleus. To study the effects on DA increase of narcotic gases, which are known to reduce some high-pressure nervous syndrome symptoms, eight and six rats were compressed in helium-nitrogen oxygen and hydrogen-helium-oxygen mixtures, respectively. They produced similar changes in striatal DA level in the same pressure range (23 and 20% increase, respectively, at the end of the compression). Consequently, the increase in striatal DA seems independent of the nature of the breathing mixture and seems related to the increase of pressure. The origin of this increase could be a pressure effect at the pre- or postsynaptic level. PMID- 7775313 TI - Multiparametric monitoring of the awake brain exposed to carbon monoxide. AB - We have applied in vivo real-time techniques to monitor the physiological changes associated with exposure to a pattern of carbon monoxide (CO) known to cause brain oxidative stress. Using a multiparametric monitoring device connected to the brain, we exposed unanesthetized rats to two levels of CO, 0.1 and 0.3% in air. Energy metabolism was evaluated by the optical monitoring of relative cerebral blood flow (CBF) and intramitochondrial redox state. Ionic homeostasis was assessed by measurements of K+,Ca2+, and H+ or Na+ levels in the extracellular space. The electrical parameters monitored were the electrocorticogram and direct current steady potential. Under 1,000 ppm of CO, the CBF was increased significantly without any measurable change in the NADH redox state, suggesting that the cause for the increased CBF was not hypoxia. Exposing the awake rat to 1,000 ppm of CO (40 min) followed by 3,000 ppm of CO (20 min) led to an increase in CBF followed by episodes of spontaneous brain depolarizations characterized by changes in ionic homeostasis and blood flow. These changes were similar to those recorded under cortical spreading depression. In most animals exposed to 3,000 ppm of CO, spontaneous oscillations in CBF and NADH redox state that were negatively correlated were recorded. The results indicate that an inspired CO level of 0.1% had effects largely restricted to blood flow, whereas at a higher CO level an additional impairment in energy supply resulted in a complex pattern of effects similar to that caused by brain ischemia. PMID- 7775314 TI - Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans. AB - In humans, endurance training reduces the rates of glucose production and utilization during moderate-intensity exercise. It is uncertain, however, whether this is also true during high-intensity exercise. Accordingly, we studied eight endurance-trained cyclists and eight untrained subjects during 30 min of cycling at approximately 80% of maximal oxygen uptake (VO2max). Rates of glucose appearance (Ra) and disappearance (Rd) were determined using a primed, continuous infusion of [6,6-2H]glucose. Average glucose Ra during exercise did not differ in the trained and untrained subjects (34.3 +/- 3.6 vs. 36.0 +/- 1.7 mumol.min-1.kg 1; mean +/- SE; P, not significant). Plasma insulin, glucagon, norepinephrine, and epinephrine concentrations were also similar in the two groups. In contrast, glucose Rd during exercise was 19% lower in the trained compared with the untrained subjects (27.0 +/- 2.6 vs. 33.2 +/- 1.5 mumol.min-1.kg-1; P < 0.001). Consequently, during exercise, plasma glucose concentration rose significantly (P < 0.05) in the trained subjects but did not change in the untrained subjects. We conclude that utilization of plasma glucose is lower in trained subjects during high-intensity exercise, even when the exercise is performed at the same relative (and therefore a higher absolute) intensity as in the untrained state. Hyperglycemia in trained subjects during intense exercise appears to be due to this lower rate of glucose utilization rather than a higher rate of glucose production. PMID- 7775315 TI - Comments on "Airway reopening pressure in isolated rat lungs". PMID- 7775316 TI - Invited editorial on "Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs". PMID- 7775317 TI - K+ and Lac- distribution in humans during and after high-intensity exercise: role in muscle fatigue attenuation? AB - This review describes processes for the distribution of K+ ([K+]) and lactate concentrations ([Lac-]) that are released from contracting muscle at high rates during high-intensity exercise. This results in increased interstitial and venous [K+] and [Lac-] in contracting muscle. Large and rapid increases in plasma [K+] and [Lac-] result in the transport of these ions into red blood cells (RBCs). These ions are distributed to noncontracting tissues within both the plasma and RBC compartments of blood. The extraction of K+ and Lac- from the circulation by noncontracting tissue serves to markedly attenuate exercise-induced increases in plasma [K+] and [Lac-]. This apparent regulation of the plasma compartment by noncontracting tissues helps to maintain favorable concentration gradients for the net movement of [K+] and [Lac-] into the venous side of the microcirculation from interstitial fluids of contracting muscle. This provides conditions that 1) reduce the increase in interstitial [K+], thereby decreasing the magnitude and rate of sarcolemmal depolarization, and 2) favor the sarcolemmal transport of Lac from within contracting muscle cells, thereby regulating intracellular osmolality and H+ concentration. On cessation of exercise, net K+ uptake by recovering muscle is rapid, with 90-95% recovery of intracellular [K+] within 3.5 min, indicating a very high rate of Na+-K+ pump activity. The K+ extracted by noncontracting tissues during exercise may be slowly released during recovery. During the initial minutes of recovery, recovering muscle continues to release Lac- into the circulation, and noncontracting tissues continue to extract Lac- for up to 30 min. The uptake of Lac- by noncontracting tissues results in elevated intracellular [Lac-]. There is no evidence that Lac- extracted by noncontracting tissues is subsequently released; it is probably metabolized within these cells. We conclude that the uptake of K+ and Lac- by RBCs and noncontracting tissues regulates ion homeostasis within plasma and the interstitial and intracellular compartments of contracting muscle. The regulatory processes help to maintain the function of active muscles by delaying the onset of fatigue during exercise and to restore homeostasis during recovery. PMID- 7775318 TI - Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs. AB - Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5-2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18%. With sodium salicylate, the mean pulmonary artery pressure dropped by 14% from control values, whereas it increased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance. PMID- 7775319 TI - Effects of endotoxin on isolated porcine liver: pressure-flow analysis. AB - The peripheral vascular response to sepsis is characterized by a vasodilatation of the systemic arterial vessels. Pulmonary hypertension with an increase in resistance and back pressure to flow defined by pressure-flow (P-Q) relationships has been reported in experimental sepsis. We hypothesized that endotoxin can induce differential alterations in resistance and back pressure to flow in the liver venous and arterial beds. Ninety minutes after endotoxin administration in intact anesthetized pigs (n = 8), the liver was vascularly isolated and perfused. Steady-state P-Q relationships in both the portal vein (PV) and hepatic artery (HA) were generated at multiple outflow pressures (Pout; 0, 5, 10, and 15 mmHg) and compared with those obtained in control livers (n = 6). Extrapolated zero flow pressure intercepts (Pback) and slopes of the P-Q relationships were obtained by least squares linear regression analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback always exceeded Pout (P < 0.05) when the latter was raised. In contrast, in controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared with control. Raising Pout from 0 to 15 mmHg decreased PV slope in the endotoxin group to a greater degree than in controls (P < 0.05). In the HA, endotoxin caused a decrease in slope but did not alter Pback. The simultaneous increase in the PV Pback and slope that occurs with endotoxemia decreases splanchnic venous return, pooling blood in the splanchnic compartment for a given total blood volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775320 TI - Metabolic and thermal adaptations from endurance training in hot or cold water. AB - Metabolic and thermal adaptations resulting from endurance training in hot vs. cold water were compared. It was hypothesized that training in hot water would have greater effects on muscle glycogen use and blood lactate accumulation during exercise than training in cold water. Eighteen men exercised at 60% of maximal oxygen uptake while immersed in hot (n = 9) or cold water (n = 9) for 1 h, 5 days/wk, for 8 wk. Training in hot water (35 degrees C) potentiated body temperature increases during exercise, and training in cold water (20 degrees C) blunted body temperature increases during exercise. Before and after training, cardiorespiratory and thermoregulatory responses and muscle glycogen and blood lactate changes were assessed during a 1-h exercise trial in hot water and, on a separate day using the same intensity, in cold water. Oxygen uptake was similar for all trials, averaging 2.0 +/- 0.1 l/min. It was observed that 1) training reduced glycogen use and lactate accumulation during exercise, with no difference between cold and hot water training groups in the magnitude of this effect; 2) lactate accumulation during exercise was the same in hot water as in cold water; and 3) skin temperature decreased more rapidly during cold-water exercise after than before training, with no difference between cold and hot water training groups in the magnitude of this effect. Thus, exercise-induced body temperature increases are not an important stimulus for glycogen-sparing effects and blunted lactate accumulation associated with endurance training. PMID- 7775321 TI - Sympathetic nervous system activity, body fatness, and body fat distribution in younger and older males. AB - It was hypothesized that an increase in total and central body fatness is related to higher sympathetic nervous system activity (SNSA) in older men. Resting SNSA was measured from norepinephrine (NE) kinetics in 69 younger (18-36 yr) and 69 healthy older men (55-80 yr). Body fat distribution was estimated from the waist circumference, body composition from underwater weighing, peak oxygen consumption from a treadmill test to exhaustion, and dietary intake from food diaries. Plasma NE concentrations were 41% higher (P < 0.001) in older men due to a 27% increase (P < 0.001) in NE appearance rate and a tendency for a lower NE clearance rate (P = 0.08). NE appearance rate was higher in individuals of both age groups who exhibited a greater waist circumference and body fatness (range of r values 0.49 0.69; P < 0.01). The waist circumference, and not age, was the strongest predictor of the increase in NE appearance rate in older men. Statistically controlling for the waist circumference or body fatness diminished age-related differences in NE concentrations and in NE appearance rate. These findings suggest that an accumulation of total and central body fat is associated with higher levels of SNSA in older males. PMID- 7775322 TI - Relationship between MRI relaxation time and muscle fiber composition. AB - The relationship between nuclear magnetic resonance relaxation time obtained with magnetic resonance imaging (MRI) and muscle fiber composition of the lateral gastrocnemius was examined in 13 men. There was a positive correlation (r = 0.80, P < or = 0.001) between longitudinal relaxation time and the relative percentage of slow-twitch muscle fibers (type I). There was no relationship between transverse relaxation time and type I percentage (r = 0.17, P = 0.57). These results suggest that MRI longitudinal relaxation time can be used for the noninvasive estimation of muscle fiber composition in humans. PMID- 7775323 TI - Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells. AB - Six adult male Sprague-Dawley rats were flown on the 7-day US space shuttle mission STS-54. After flight, the spleen and thymus from each animal were assayed for the capacity to secrete the cytokines interleukin-3 (IL-3) and IL-6. Spleen and thymus cells (5 x 10(6)/ml) were incubated for 48 h in the presence of 5 micrograms/ml of concanavalin A or 2 micrograms/ml of bacterial lipopolysaccharide to stimulate the production of IL-3 and IL-6. IL-3 activity was measured using the IL-3/colony-stimulating-factor-dependent cell line 32D. IL 6 activity was measured using the IL-6-dependent cell line 7TD1. Spleen and thymus cells harvested from flown rats secreted significantly higher titers of biologically active IL-3 compared with ground control rats. Spaceflight significantly enhanced IL-6 production by thymus, but not spleen, cells. The results of this study demonstrate that spaceflight can enhance the production of certain cytokines by cells of the immune system. PMID- 7775324 TI - Influence of isometric loading on biceps EMG dynamics as assessed by linear and nonlinear tools. AB - The summed electrical discharges generated by a contracting skeletal muscle constitute a dynamic system conveying electromyographic (EMG) information indicative of muscle physiological status. "Steady states" of activity can be achieved with light loads, but with heavy loads the dynamic system experiences continuous status transitions that culminate in task failure. The present study was designed to assess the applicability of two mathematical tools, one linear and the other nonlinear, in addressing the time course of EMG alterations under different loading challenges. Surface EMGs of the biceps brachii muscle were recorded from 14 healthy human volunteers during light and heavy loadings, and task failure occurred at varying times among the subjects. Digitized EMG signals were analyzed by linear spectral analysis (fast Fourier transform) and nonlinear recurrence-plot analysis. With light loading, computed variables from both analyses gave "quasi-steady-state" values over time, with recurrence-plot analysis having the higher variance. With heavy loading, the nonlinear variable (%determinism) increased sooner and exhibited larger changes from control values than decreases in the linear variable (spectral center frequency). Experimental results support the conclusion that both analyses can be combined to give a fuller assessment of the biceps EMG during light or heavy loading. Implications for the detection of muscular fatigue are discussed. PMID- 7775325 TI - Skeletal muscle characteristics among distance runners: a 20-yr follow-up study. AB - The purpose of this investigation was to examine the histochemical and enzymatic characteristics of skeletal muscle after 20 yr of distance running training. Twenty-eight men were first studied between 1966 and 1974 when they were all highly trained distance runners. On the basis of their training regimens in the interim between testing, subjects were described as highly trained (HI; n = 11), fitness trained (FIT; n = 10), or untrained (UT; n = 7). Gastrocnemius muscle biopsy samples revealed a mean increase (P < 0.05) in the proportion of type I fibers of the FIT and UT groups, whereas the HI group, which was initially characterized by a high percentage (> 70%) of type I fibers, was unchanged. Although the mean fiber type change of the HI group was similar between evaluations, 6 of the 11 subjects did elicit an increase in the percentage of type I fibers. A subgroup of elite distance runners who had continued to train for competition experienced an approximately 25% reduction (P > 0.05) in muscle succinate dehydrogenase activity and decreases (P > 0.05) in types I and II muscle fiber areas. On the average, in 1993 the HI group had higher (P < 0.05) succinate dehydrogenase and citrate synthase activities than the FIT and UT groups, whereas phosphorylase activity did not differ among the three groups. These data suggest that the middle-aged men in this study had a significantly greater proportion of type I muscle fibers than when they were 20 yr younger.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775327 TI - Regional pulmonary blood flow during rest, tilt, and exercise in unanesthetized dogs. AB - We assessed the heterogeneity of regional pulmonary blood flow (PBFr), using radioactive microspheres in five unanesthetized dogs standing at rest (Rest), standing at a 45 degrees upward tilt (Tilt), and during moderate treadmill exercise (Exer). The excised lungs were cut into 1-cm3 pieces along transverse, horizontal, and longitudinal planes. Mean PBFr increased from 23.3 ml.min-1.g-1 at Rest to 57.4 ml.min-1.g-1 during Exer, but the relative dispersions were not statistically different between states (47.3-51.9%). A small but significant gravity-dependent gradient in PBFr of < or = 4.7%/cm (r2 < or = 0.118) as well as a PBFr decreasing radial gradient from the lung midpoint of < or = 7.2%/cm (r2 < or = 0.108) were present in all states. PBFr at Rest was highly correlated with those at Tilt (r2 = 0.773) and Exer (r2 = 0.888), and a variable PBFr gradient of < or = 2.5%/cm from base to apex was observed. Fractal dimensions calculated using relative dispersion as a function of aggregated sample size were not significantly different between states and were 1.132 (r2 = 0.987) at Rest, 1.121 (r2 = 0.973) at Tilt, and 1.149 (r2 = 0.986) during Exer. Thus, gravity and centripetal gradients consistently accounted for a maximal difference of only about twofold in PBFr and < 11% of overall PBFr heterogeneity in 1-cm3 samples. Recursive anatomic branching of pulmonary arteries and local mechanical factors apparently account for most of the blood flow heterogeneity in small pieces of lung. PMID- 7775326 TI - Electrochemical detection of rapid DA release kinetics during hypoxia in perfused superfused cat CB. AB - The hypothesis that hypoxic excitation is coupled to dopamine (DA) secretion was tested in perfused-superfused cat carotid bodies (CB). DA was electrochemically detected by an amperometric method (constant applied potential +150 mV) with Nafion polymer-coated recessed gold microsensors (tip diameter 3-8 microns) in 10 cat CBs. Neural discharge (ND) from the whole sinus nerve was measured simultaneously with DA changes during interruption of perfusate flow and during hypoxic perfusion (5% O2). A computer-controlled instrument using a chronoamperometric technique (+550-mV pulses) with a Nafion-coated carbon fiber microelectrode (tip diameter 35 microns) was used to detect DA changes in two CBs during similar hypoxic stimuli. Rapid DA release kinetics were measured during flow interruption with an initial rate of 1.05 +/- 0.15 (SE) microM/s within the first 10-15 s. At most measurement sites, the increase in DA preceded the rise in ND. After the initial increase, DA release slowed to 0.16 +/- 0.02 microM/s, reaching a maximum DA concentration of 20.7 +/- 2.6 microM above baseline after 90 s of flow interruption. Nicotine (10-micrograms bolus) caused a large increase in ND without a proportional increase in DA release. Spatially detailed time resolved electrochemical measurements were able to discriminate between DA release during hypoxia and chemoexcitatory responses that do not involve DA release. PMID- 7775328 TI - Short-term immobilization has a minimal effect on the strength and fatigability of a human hand muscle. AB - The purpose of this study was to determine the association between reduced fatigability typically observed in disused muscle and an improved resistance to the impairment of neuromuscular propagation. Endurance time of an isometric contraction sustained at 35% of maximum voluntary contraction (MVC) force and the fatigue-induced change in the evoked compound muscle action potential (M wave) were measured in the first dorsal interosseus muscle of human subjects before, during, and after 3 (n = 9) or 5 wk (n = 2) of immobilization. The immobilization procedure caused a substantial decline in the chronic electromyographic (EMG) activity (to 4% of control value) of the first dorsal interosseus muscle. Endurance time was found to be significantly correlated to the maintenance of M wave amplitude during the fatigue task. However, neither of these variables was significantly affected by immobilization. Also, immobilization had no significant effect on the prefatigue values of MVC force and EMG or twitch contraction time or on the postfatigue changes in MVC force and EMG, M wave duration, twitch amplitude, and contraction time. In the unfatigued muscle, immobilization did cause an increase in twitch force (153%) and a decrease in M-wave amplitude (67%). It appears, therefore, that a healthy first dorsal interosseus muscle is generally resistant to adaptation when its use has been reduced for 3-5 wk by immobilization. PMID- 7775329 TI - Activity of respiratory neurons during hypoxia in the chemodenervated cat. AB - Exposure of anesthetized paralyzed vagotomized peripherally chemodenervated cats to hypoxia results in initial depression and subsequent loss of the phrenic neurogram. To determine whether hypoxic respiratory depression results from the inhibition of respiratory premotor neurons by bulbospinal neurons of the Botzinger complex (Bot-E neurons), extracellular recordings were made of dorsal and ventral respiratory group bulbospinal inspiratory neurons and Bot-E neurons during acute hypoxic hypoxia. All neurons recorded decreased firing rate during hypoxia. Bot-E neurons became silent before the loss of phasic phrenic activity during hypoxia and commenced firing before or coincident with the return of the phrenic neurogram during reoxygenation. Inspiratory neurons ceased firing coincident with phrenic silence. Dorsal respiratory group and ventral respiratory group neurons that had a late onset of firing with respect to the phrenic neurogram during normoxia fired progressively earlier in inspiration during hypoxia, an effect that was reversed during reoxygenation. These data are consistent with inhibition and/or disfacilitation as the mechanism of hypoxic respiratory depression but suggest that Bot-E neurons are not the source of this inhibition. PMID- 7775330 TI - Fractal analysis of surfactant deposition in rabbit lungs. AB - The effect of exogenous surfactant in the treatment of acute lung injury may depend on homogeneity of distribution of the material delivered. Analyses of distribution rely on sectioning the lung, determining surfactant concentration for each piece, and describing the variation in that value. Results of such analyses are influenced by how finely the lung is sectioned. We have reanalyzed data from prior experiments to determine whether the distribution of administered surfactant is fractal, that is, is independent of the scale of measurement. Lungs from animals receiving surfactant radiolabeled with [3H]dipalmitoylphosphatidylcholine were cut into 108 pieces, and the normalized radioactivity in each piece was determined. Sectioning of the lungs into different numbers of pieces (n = 2, 6, 12, 18, 36, 54, or 108) was simulated, and corresponding radioactivity contents were calculated. The coefficient of variation (CV) of these normalized values was then calculated for each scale of measurement (expressed as relative piece volume), and ln(CV) was plotted as a function of the logarithm of relative piece volume. These relationships were linear (average correlation coefficient = 0.96) for all animals, consistent with CV being a fractal property. We conclude that the intrapulmonary distribution of surfactant may be fractal and is therefore a property of the lung. This study demonstrates the utility of fractal analysis in describing the pulmonary distribution of substances introduced via the airway. PMID- 7775331 TI - Metabolic, catecholamine, and exercise performance responses to various doses of caffeine. AB - This study examined the exercise responses of well-trained endurance athletes to various doses of caffeine to evaluate the impact of the drug on exercise metabolism and endurance capacity. Subjects (n = 8) withdrew from all dietary sources of caffeine for 48 h before each of four tests. One hour before exercise they ingested capsules of placebo or caffeine (3, 6, or 9 mg/kg), rested quietly, and then ran at 85% of maximal O2 consumption to voluntary exhaustion. Blood samples for methylxanthine, catecholamine, glucose, lactate, free fatty acid, and glycerol analyses were taken every 15 min. Plasma caffeine concentration increased with each dose (P < 0.05). Its major metabolite, paraxanthine, did not increase between the 6 and 9 mg/kg doses, suggesting that hepatic caffeine metabolism was saturated. Endurance was enhanced with both 3 and 6 mg/kg of caffeine (increases of 22 +/- 9 and 22 +/- 7%, respectively; both P < 0.05) over the placebo time of 49.4 +/- 4.2 min, whereas there was no significant effect with 9 mg/kg of caffeine. In contrast, plasma epinephrine was not increased with 3 mg/kg of caffeine but was greater with the higher doses (P < 0.05). Similarly only the highest dose of caffeine resulted in increases in glycerol and free fatty acids (P < 0.05). Thus the highest dose had the greatest effect on epinephrine and blood-borne metabolites yet had the least effect on performance. The lowest dose had little or no effect on epinephrine and metabolites but did have an ergogenic effect. These results are not compatible with the traditional theory that caffeine mediates its ergogenic effect via enhanced catecholamines. PMID- 7775332 TI - Changes in regional lung impedance after intravenous histamine bolus in dogs: effects of lung volume. AB - We measured the effect of lung volume on the time course of regional lung input impedance (ZA) after bolus intravenous administration of 2 mg of histamine in seven open-chest dogs using alveolar capsule oscillators. ZA (24-200 Hz) was obtained during apnea at constant lung volume every 2 s for 80 s at lung inflation pressures of 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 kPa. Local airway resistance (RA) and elastance of the local lung region were calculated by fitting a four-parameter model to the measured ZA. Total lung resistance and lung elastance were also calculated from tracheal pressure and flow measured during mechanical ventilation (0.3 Hz) just before and after each set of ZA measurements. We found the histamine-induced changes in both lung resistance and lung elastance to decrease with increasing lung volume. RA also showed a large negative dependency on lung volume, and the variation between different RA measurements became markedly increased as lung volume decreased. In contrast, local airway elastance was essentially unaffected by lung volume. These results support the idea that parenchymal tethering of the very distal airways impedes their narrowing during bronchoconstriction. They also indicate that reduced parenchymal tethering causes airway narrowing to become markedly more inhomogeneous. PMID- 7775333 TI - Sympathetic nerve responses to hyperthermia in the anesthetized rat. AB - The aim of the present study was to characterize the sympathetic nerve responses to hyperthermia in chloralose-anesthetized rats. Discharges were recorded from the renal, lumbar, and splanchnic sympathetic nerves. Mean arterial pressure, heart rate, and sympathetic nerve discharge (SND) were recorded continuously during progressive increases in core body temperature (Tc) from 38.0 to 41.0 degrees C. The following observations were made: 1) significant increases in renal, lumbar, and splanchnic SND were observed during hyperthermia; 2) autospectral analysis of renal and lumbar SND revealed that the frequency distribution of SND can be altered during progressive increases in Tc; and 3) increases in splanchnic SND to acute heating were similar in baroreceptor innervated and -denervated rats. We conclude that 1) hyperthermia is a potent stimulus to the sympathetic nervous system and increases the activity in three sympathetic nerves that innervate different regional arterial beds, 2) acute heating influences the neural circuits involved in generating SND as evidenced by changes in the basic pattern of renal and lumbar SND, and 3) the increase in splanchnic SND during hyperthermia is not opposed by the arterial and cardiopulmonary baroreceptors. PMID- 7775334 TI - Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. AB - To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22-86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of approximately 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age approximately 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise. PMID- 7775336 TI - Flow pulsatility does not increase mean microvascular pressure or filtration in zone 3 rabbit lungs. AB - We previously reported that mean pulmonary arterial pressure (Ppa) during pulsatile flow exceeded that for steady flow when flow was greater than the normal resting value and speculated that this was due to irregularities of the flow profiles in precapillary vessels, mainly the larger arteries. From this we hypothesized that neither mean microvascular pressure nor the rate of fluid filtration would be affected by flow pulsatility. We therefore compared the effects of steady vs. pulsatile flow on the double-occlusion pressure (Pdo) and on edema formation (rate of weight gain) in zone 3 rabbit lungs. Excised left lungs (n = 19) were perfused with Tyrode solution and ventilated with an end expiratory pressure of 2.5 cmH2O. A diaphragm pump generated pulsatile flow with a stroke volume of 1.0 ml (approximately 0.8 the normal resting value for rabbit left lung). Nonpulsatile flow was generated by raising an arterial reservoir. Flow rate was set at 100 or 400 ml/min (approximately 0.4 or 1.6 x the normal resting cardiac output, respectively). Vascular pressures (referenced to the bottom of the lung) were measured after ventilation, at end expiration, was interrupted. Pdo values were obtained in random order at 15 time points that were evenly distributed within the pulse cycle, averaged across pulses to obtain the mean capillary pressure profile, and then averaged over time. At the lower flow of 100 ml/min, mean Ppa and Pdo were slightly lower (3-4%) during pulsatile compared with nonpulsatile conditions. At the higher flow of 400 ml/min, mean Ppa was higher under pulsatile conditions (13%), whereas downstream the mean Pdo values were equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775335 TI - Reduced motor unit activation of muscle spindles and tendon organs in the immobilized cat hindlimb. AB - Six weeks of limb immobilization of a healthy muscle (cat tibialis posterior) at a short length resulted in a significant reduction of mean fiber area for all fiber types (I, 71% of control; IIa, 77% of control; IIb, 79% of control), whereas fiber type proportions were unchanged. For motor units, there was a reduction in peak tetanic force (type slow > fast fatigue resistant > fast fatigable); an increase in the twitch-to-tetanus ratio for fast fatigue-resistant and slow units; and no effect on the twitch force, twitch time course, or fatigability. The reduction in peak force was greater than expected because of fiber atrophy in slow units. Immobilization had a minimal effect on muscle spindle afferent (Ia and spindle group II) responses to a ramp-and-hold stretch of the passive muscle. Tendon organ (Ib) afferents had an increased responsiveness to stretch after immobilization but only when the muscle was stretched from a short resting length. However, immobilization reduced the modulation of muscle afferent discharge in response to tetanic contractions of single motor units. The decline in responsiveness of spindles was a result of the reduced tetanic force of motor units. In contrast, tendon organs in immobilized muscle were twice as likely to convey no information on the contraction of a single motor unit and were more likely to be unloaded, suggesting that immobilization caused the functional denervation of some muscle fibers. Thus the responses of muscle spindles and tendon organs in immobilized muscle reflected atrophic changes in extrafusal fibers but did not provide evidence for substantial disturbance of receptor function. PMID- 7775337 TI - Role of neutral endopeptidase in bronchial hyperresponsiveness to bradykinin induced by IL-1 beta. AB - Interleukin-1 beta (IL-1 beta) induces bronchial hyperresponsiveness (BHR) to bradykinin but not to acetylcholine. We examined whether this was mediated through the inhibition of neutral endopeptidase (NEP) activity and/or through the enhancement of airway microvascular leakage (AML) by IL-1 beta. We administered human recombinant IL-1 beta (500 U) or saline intratracheally and 24 h later measured the airway responses to bradykinin (1 mM; 45 breaths). IL-1 beta-treated rats showed a decrease of 18.5 and 21.1% of NEP activity in the lungs and tracheobronchial tree, respectively (P < 0.05), associated with an augmented response in total lung resistance to bradykinin but with no increase in Evans blue dye extravasation used as a marker of AML. Phosphoramidon (0.1 and 1 mM; 90 breaths), an NEP inhibitor, induced a dose-dependent increase in lung resistance to bradykinin without further enhancing BHR induced by IL-1 beta. Bradykinin induced AML was not enhanced by phosphoramidon in either saline- or IL-1 beta treated rats. Similarly, after captopril (1 mM; 90 breaths), an inhibitor of angiotensin-converting enzyme, there was no further enhancement of BHR to bradykinin induced by IL-1 beta. BHR to bradykinin induced by IL-1 beta may result from an inhibition of peptidase activity, such as NEP and angiotensin converting enzyme, and is not associated with an enhancement of AML. PMID- 7775338 TI - Gas density does not affect pulmonary acoustic transmission in normal men. AB - Fremitus, the transmission of sound and vibration from the mouth to the chest wall, has long been used clinically to examine the pulmonary system. Recently, modern technology has become available to measure the acoustic transfer function (TF) and transit times (TT) of the pulmonary system. Because sound speed is inversely proportional to the square root of gas density in free gas, but not in porous media, we measured the effect of air and Heliox (80% He-20% O2) breathing on pulmonary sound transmission in six healthy subjects to investigate the mechanism of sound transmission. Wide-band noise (75-2,000 Hz) was "injected" into the mouth and picked up over the trachea and chest wall. The averaged power spectra, TF, phase, and coherence were calculated using a fast Fourier transform based algorithm. The phase data were used to calculate TT as a function of frequency. TF was found to consist of a low-pass filter property with essentially flat transmitted energy to 300 Hz and exponential decline to 600 Hz at the anterior right upper lobe (CR) and flat transmission to 100 Hz with exponential decline to 150 Hz at the right posterior base (BR). TF was not affected by breathing Heliox. The average TT values, calculated from the slopes of the averaged phase, were 1.5 +/- 0.5 ms for trachea to CR and 5.2 +/- 0.5 ms for trachea to BR transmission during air breathing. During Heliox breathing, the values of TT were 1.5 +/- 0.5 ms and 4.9 +/- 0.5 ms from the trachea to CR and from the trachea to BR locations, respectively. These results suggest that sound transmission in the respiratory system is dominated by wave propagation through the parenchymal porous structure. PMID- 7775339 TI - T model partition of lung and respiratory system impedances. AB - The aim of this work was to demonstrate that the three compartments of the lung T network and the chest wall impedance (Zcw) can be identified from input and transfer impedances of the respiratory system if the pleural pressure is recorded during the measurements. The method was tested in six healthy volunteers in the range of 8-32 Hz. The impedances resulting from the decomposition confirm the adequacy of the monoalveolar structure commonly used in healthy subjects. Indeed, the T shunt impedance is well modeled by a purely compliant element, the mean compliance [0.038 +/- 0.081 (SD) l/kPa], which coincides within 9.5 +/- 6.3% of the alveolar gas compressibility derived from thoracic gas volume (0.036 +/- 0.011 l/kPa). The results obtained provide experimental evidence that the alveolar gas compression is predominantly isothermal and that lung tissue impedance is negligible throughout the whole frequency range. The shape of Zcw is consistent with a low compliance-low inertance pathway in parallel with a high compliance-high inertance pathway. We conclude that the proposed method is able to reliably identify the T network featuring the lung and Zcw. PMID- 7775340 TI - Skin of the dorsal aspect of human hands and fingers possesses an active vasodilator system. AB - To test for an active vasodilator system in human hand and finger skin, seven subjects had a small area of dorsal hand, palm, or dorsal finger pretreated with bretylium (BT) to block adrenergic vasoconstriction. Skin blood flow was monitored at a BT-treated site, a comparable untreated site, and the forearm by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to arterial pressure. Body cooling, to evaluate vasoconstrictor system blockade, caused CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger to fall by 45 +/- 4, 85 +/- 5, 51 +/- 9, and 63 +/ 7%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, reductions in CVC were only 13 +/- 3, 2 +/- 18, and 13 +/- 4%, respectively (dorsal hand not significant, others P < 0.05). With body heating, increases in CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger were 881 +/- 165, 779 +/- 368, 423 +/- 115, and 1,430 +/- 716%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, increases were 35 +/- 15, 342 +/- 107, and 343 +/- 34%, respectively (palm not significant, others P < 0.05). Increased CVC at the palm began after 1.2 +/- 0.2 min of heating, significantly earlier than forearm (11.8 +/- 2.5 min), dorsal hand (16.4 +/- 3.4 min), or dorsal finger (15.6 +/- 3.6 min), which did not differ significantly from one another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775341 TI - Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment. AB - We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age. PMID- 7775342 TI - Performance and excitability of mdx mouse muscle at 2, 5, and 13 wk of age. AB - Dystrophin is a 427-kDa protein localized adjacent to the sarcolemma in skeletal muscle. Its physiological role remains uncertain, although its absence is known to cause muscular dystrophy. In this study, the function of dystrophin was investigated using the dystrophin-deficient mdx mouse. Control and mdx animals at 2, 5, and 13 wk of age (n = 8-11/age) were compared to evaluate in situ gastrocnemius-plantaris-soleus muscle contractile, endurance, and excitability properties at nondegenerated, degenerated, and regenerated stages, respectively. Twitch and tetanic tensions expressed per gram of muscle mass were lower in mdx muscle only at 5 wk. Fatigue produced during successive contractions at 2, 10, and 20 Hz did not differ between the two groups at 2 and 5 wk but was lower in mdx muscle at 13 wk. This was not attributed to differences in mitochondria, since cytochrome-c oxidase activity was similar in mdx and control muscle. Contractile properties of control and mdx muscle became faster with age, and at 13 wk the time to peak twitch tension was shorter in mdx muscle relative to control, whereas the half-relaxation times did not differ. Mass action potential area (M wave), an index of muscle excitability, was not significantly different between mdx and control muscle at 2 or 5 wk but was greater in mdx muscle at 13 wk. Thus, in this weight-bearing muscle group, the lack of dystrophin has only a moderate impact in modifying muscle function relative to contractile properties, fatigability, or excitability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775343 TI - The effects of rM-CSF and rIL-6 therapy on immunosuppressed antiorthostatically suspended mice. AB - Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of antiorthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors. PMID- 7775344 TI - Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations. AB - Thirty-five healthy men were matched and randomly assigned to one of four training groups that performed high-intensity strength and endurance training (C; n = 9), upper body only high-intensity strength and endurance training (UC; n = 9), high-intensity endurance training (E; n = 8), or high-intensity strength training (ST; n = 9). The C and ST groups significantly increased one-repetition maximum strength for all exercises (P < 0.05). Only the C, UC, and E groups demonstrated significant increases in treadmill maximal oxygen consumption. The ST group showed significant increases in power output. Hormonal responses to treadmill exercise demonstrated a differential response to the different training programs, indicating that the underlying physiological milieu differed with the training program. Significant changes in muscle fiber areas were as follows: types I, IIa, and IIc increased in the ST group; types I and IIc decreased in the E group; type IIa increased in the C group; and there were no changes in the UC group. Significant shifts in percentage from type IIb to type IIa were observed in all training groups, with the greatest shift in the groups in which resistance trained the thigh musculature. This investigation indicates that the combination of strength and endurance training results in an attenuation of the performance improvements and physiological adaptations typical of single-mode training. PMID- 7775345 TI - Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of beta-receptors. AB - To evaluate the adenosine systems ability to reverse the endothelial damage produced by ischemia and reperfusion (I/R), we studied several different selective adenosine-receptor agonists and antagonists, a protein kinase A inhibitor, and a beta-adrenoreceptor antagonist in isolated buffer-perfused rat lungs. I/R (45 min/105 min) produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Both a selective A2-receptor agonist (CGS-21680, 300 nM) and a beta-receptor agonist (isoproterenol, 10 microM) reversed the increased microvascular permeability. A nonselective adenosine-receptor antagonist (SPT, 20 microM) and a selective A1 receptor antagonist (DPCPX, 10 nM) had no effect on increased microvascular permeability. Also, isoproterenol and CGS-21680 reversed the damage being introduced after a selective A1-receptor agonist (CCPA, 100 nM). The nonspecific adenosine A1- and A2-receptor agonist NECA (12 nM) appeared to desensitize the A2 receptors and a protein kinase A inhibitor, adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS, 100 microM), blocked the reversal of endothelial damage by isoproterenol or A2-receptor agonist. Propranolol (100 microM) blocked the effect of isoproterenol but not the effect of CGS-21680. From this study we conclude that A2-receptor activation reverses endothelial damage associated with I/R by a mechanism independent of beta-receptors or Gi protein. However, a protein kinase A-3',5',-cyclic adenosine monophosphate pathway is activated by both the adenosine systems and beta-receptor activation. PMID- 7775347 TI - Testosterone and aggression. PMID- 7775348 TI - Of norms and cutoffs. PMID- 7775346 TI - Effects of increased +Gz on chest wall mechanics in humans. AB - We studied the effects of head-to-foot acceleration (+Gz) on chest wall mechanics in five normal subjects seated in a human centrifuge. Results were compared with those previously obtained in the same subjects in microgravity during parabolic flights. In all subjects, end-expiratory abdominal pressure (Pga) and volume (Vab) increased with Gz. On average, end-expiratory Pga increased from 7.4 +/- 1.7 cmH2O at + 1 Gz to 14.9 +/- 2.8 cmH2O at + 3 Gz and end-expiratory Vab increased by 0.32 +/- 0.06 liter between + 1 and + 3 Gz. On the other hand, the abdominal contribution to tidal volume (Vab/VT) and abdominal compliance decreased from 34.7 +/- 5.9% and 52 +/- 6 ml/cmH2O at + 1 Gz to 29.3 +/- 5.1% and 26 +/- 4 ml/cmH2O at + 3 Gz, respectively. Changes in end-expiratory Pga were linear between 0 and + 3 Gz, but changes in end-expiratory Vab, Vab/VT, and abdominal compliance were greater in microgravity than in hypergravity. In contrast to weightlessness, which did not alter minute ventilation and tidal changes in Pga and transdiaphragmatic pressure, these variables increased with increasing Gz. These results indicate that, although changes in Gz have a linear effect on abdominal transmural pressure, hypergravity and weightlessness do not have symmetrical effects on chest wall mechanics. PMID- 7775349 TI - Comorbid Capgras' syndrome. PMID- 7775350 TI - PDD and Prader-Willi syndrome. PMID- 7775351 TI - A developmental psychopathology perspective on child abuse and neglect. AB - OBJECTIVE: The purpose of this review is to conceptualize child abuse and neglect within a developmental psychopathology perspective. Toward this end, issues of definition and epidemiology, etiology, and sequelae are addressed. METHOD: Research and theory on child abuse and neglect with relevance to a developmental perspective is reviewed. RESULTS: Considerable progress has been made in our understanding of the etiology and consequences of child abuse and neglect. Less progress has been made in utilizing this knowledge to inform treatment efforts. CONCLUSIONS: Incorporation of a developmental psychopathology perspective into efforts to understand and ameliorate the adverse effects of child abuse and neglect holds considerable promise for advancing research and intervention in the area of child maltreatment. The importance of providing comprehensive and coordinated services that incorporate knowledge of how maltreated youngsters negotiate stage-salient issues of development is stressed. The provision of child focused treatment, parent-based models of intervention, and ecologically driven approaches to prevention all can benefit from an understanding of the adverse effects that maltreatment exerts on the process of development. PMID- 7775352 TI - Unipolar depression in adolescents: clinical outcome in adulthood. AB - OBJECTIVE: This study examined the longitudinal clinical course and adult sequelae of adolescent unipolar major depressive disorder (MDD) using a controlled longitudinal design. METHOD: Subjects were 28 adolescents (15.4 +/- 1.3 years) with systematically diagnosed unipolar MDD and 35 group-matched control subjects who participated in a cross-sectional electroencephalogram sleep and neuroendocrine study. Using standardized instruments, interviewers who were blind to subjects' initial diagnoses conducted follow-up clinical assessments 7.0 +/- 0.5 years later in 94% of the original cohort. RESULTS: The depressed group showed high rates of recurrence of MDD episodes during the interval period (69%). They also had elevated rates of new-onset bipolar disorder (19%). Twenty-three percent of subjects with an initial diagnosis of MDD had no additional depressive episodes after the index assessment. The rate of new onset of depression in the controls was 21%. Low socioeconomic status predicted recurrence of depressive episodes in the MDD group. MDD subjects with recurrence(s) and controls with new onset of depression during the follow-up period had significant psychosocial morbidity, as evidenced by disruption in interpersonal relationships and dissatisfaction with life and decrease in global functioning, compared with both MDD subjects with no further episodes and control subjects who had never been psychiatrically ill. These psychosocial deficits persisted remission from depressive episode(s). CONCLUSIONS: Adolescent unipolar MDD predicts continued risk for recurrences with persistence of depressive episodes and psychosocial morbidity into adulthood. A sizable minority, however, have sustained periods of remission associated with good social adjustment. PMID- 7775353 TI - Psychiatric comorbidity among referred juveniles with major depression: fact or artifact? AB - OBJECTIVE: The high levels of psychiatric comorbidity reported in juveniles meeting operational definitions of depressive disorders raise both substantive and methodological concerns about whether depression with comorbid disorders should be classified as two disorders or as different manifestations of the same condition. Our purpose was to clarify issues of diagnostic heterogeneity and diagnostic overlap in juvenile depression. METHOD: The sample consisted of consecutively referred children and adolescents (N = 424) comprehensively evaluated with structured diagnostic interviews and psychosocial assessments. RESULTS: A clinical picture compatible with the diagnosis of major depression was identified in 40% of these referred youths. Children meeting criteria for major depression had prototypical symptoms of the disorder, a chronic course, and severe psychosocial dysfunction. In addition, they frequently met criteria for attention-deficit hyperactivity disorder, conduct disorder, and anxiety disorders. These comorbidity findings were not due to symptom overlap among major depression and the co-occurring disorders. For the most part, comorbid disorders preceded the onset of major depression by several years. CONCLUSIONS: Juvenile depression has a chronic course, severe dysfunction, and high levels of psychiatric comorbidity. Despite symptom overlap, our work suggests that major depression and other conditions may represent different disorders. PMID- 7775354 TI - Stressful life events in depressed adolescents: the role of dependent events during the depressive episode. AB - OBJECTIVE: To examine the relationship between stressful life events and major depressive disorder (MDD) in adolescents. METHOD: Adolescents (aged 12 to 18 years) with a current episode of MDD based on Research Diagnostic Criteria (n = 39) and normal controls free of any Axis I lifetime psychiatric disorder (n = 35) were assessed using the Life Events Record. RESULTS: MDD and normal control adolescents had similar rates of total stressful life events in the year before being interviewed. Stressful life events were dichotomized into those that were most likely either independent of or dependent on the adolescent's influence/behavior. Depressed adolescents had significantly more dependent stressful life events during the previous year than did the normal controls. Further analyses showed that depressed adolescents with dependent stressful life events scored lower on symptom clusters and accordingly were less severely depressed than depressed adolescents without dependent life events. CONCLUSIONS: The results of this study indicate that depressed adolescents have an increased risk for experiencing dependent life events. Furthermore, these data suggest that dependent life events in depressed adolescents are differentially associated with the type and severity of symptom presentation. The temporal occurrence, severity, and type of stressful life events as they relate to the onset, phenotypic expression, and maintenance of depression in adolescents need to be more fully understood. PMID- 7775355 TI - Early psychosocial risks for adolescent suicidal ideation and attempts. AB - OBJECTIVE: An ongoing, 14-year, longitudinal community study examined psychosocial risks for adolescent suicidal ideation and attempts, as well as the link between earlier suicidal behavior and later functioning. METHOD: Nearly 400 youths were followed between the ages of 5 and 18 years. Suicidal ideation was assessed at age 15 and lifetime suicide attempts were determined at age 18. Risk factors covered developmental periods from birth to age 15, and most were measured prospectively using multiple informants. Late-adolescent functioning (at age 18) was based on both self-reports and school records. RESULTS: For both genders, the early onset (by age 14) of psychiatric disorders significantly increased the risk for suicidal ideation at age 15 and suicide attempts by age 18. Early gender-specific risks for suicidal ideation included preschool behaviors that are counter to typical gender norms, such as aggressive behavior in females and dependence in males. Suicidal ideation at age 15 and suicide attempts were both associated with deficits in later adolescence (at age 18) in behavioral and social-emotional functioning. CONCLUSIONS: Suicidal ideation at age 15 was a marker of distress with long-term implications for later functioning. The early gender-specific risk factors for suicidal behavior identified in this study can aid in developing strategies for prevention and early intervention. PMID- 7775357 TI - Adolescents' image of their suicide attempt. AB - OBJECTIVE: To inventory the reasons adolescents give for their perceptions of events, thoughts, and feelings in the last days and hours before and during the attempt. METHOD: A semistructured interview also included the administration of an instrument that contained the formulation of reasons. RESULTS: The most frequently mentioned reasons for attempting suicide concerned the cessation of (an unbearable) consciousness. The motivation most frequently named for "crossing the bridge" between thinking about and attempting suicide involved an escalation of frustration and tension. CONCLUSIONS: Special emphasis should be given to family relationships, relationships with peers and friends, frustration tolerance, and the way in which adolescents handle their problems. PMID- 7775358 TI - Comparison of diagnostic criteria for attention deficit disorders in a German elementary school sample. AB - OBJECTIVE: This study compares teacher-reported prevalence rates for disruptive behavior disorders using DSM-IV, DSM-III-R, and DSM-III criteria within the same population of elementary school students and examines the relationships between DSM "subtypes" and academic performance, perceived behavior problems, and demographic variables. METHOD: Teacher rating scales were obtained on 1,077 students in five rural and five urban public schools in Regensburg, Germany. Rating scales included DSM-III-R items (attention-deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder), DSM-IV items (attention deficit/hyperactivity disorders [AD/HDs], oppositional defiant disorder), and DSM III items (attention deficit disorder, with and without hyperactivity). Factor analyses of significance were performed. RESULTS: Overall prevalence for attention deficit disorders increased from 9.6% (DSM-III) to 17.8% (DSM-IV) primarily because of new cases identified as AD/HD-AD (inattentive type) and to a lesser degree, AD/HD-HI (hyperactive-impulsive type). Inattention in any subtype was associated with academic problems, and perceived behavior problems were associated with more than 80% of the cases that included hyperactivity impulsivity. DSM-IV AD/HD subtypes showed significant behavioral, academic, and demographic differences. CONCLUSION: Application of DSM-IV criteria increased total AD/HD prevalence rates by 64% and identified the majority of children with academic and/or behavioral dysfunction. The data show significant heterogeneity between the subtypes and imply that many children screened into these subtypes require further evaluation to ensure appropriate management. PMID- 7775356 TI - Childhood circumstances, adolescent adjustment, and suicide attempts in a New Zealand birth cohort. AB - OBJECTIVE: To estimate the prevalence of attempted suicide during adolescence in a birth cohort of New Zealand children studied to the age of 16 years and to examine the relationships among adolescent problems of adjustment, psychopathology, childhood circumstances, and risks of adolescent suicide attempts. METHOD: Attempted suicide, adolescent problems of adjustment, psychopathology, and childhood circumstances were assessed as part of a longitudinal study of a birth cohort of 954 New Zealand children studied at annual intervals to the age of 16 years. RESULTS: By 16 years, 3.0% of the sample (4.2% of girls and 1.9% of boys) reported having made a suicide attempt. There were strong associations between attempted suicide and rates of adolescent problem behaviors or psychopathology; teenagers having problems of adjustment or psychiatric disorders were up to 22 times more likely to attempt suicide. Risks of attempted suicide were also higher among children from disadvantaged or dysfunctional family backgrounds. A loglinear model fitted to the measures of attempted suicide, adolescent psychopathology, problems of adjustment, and childhood circumstances suggested the presence of a causal chain process in which childhood problems were significantly (p < .005) related to increased risks of later psychopathology and problems of personal adjustment which were, in turn, related to significantly (p < .05) increased rates of attempted suicide. CONCLUSIONS: A common pathway that leads to increased vulnerability to suicidal behavior involves early disadvantageous childhood and family circumstances, which lead to increased risks of adolescent psychopathology and problems of adjustment, which lead to increased risks and vulnerability to adolescent suicidal behaviors. PMID- 7775359 TI - Test of four hypotheses for the comorbidity of attention-deficit hyperactivity disorder and conduct disorder. AB - OBJECTIVE: To study the basis of the comorbidity of two common psychiatric disorders of childhood: attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD). METHOD: Subjects were 45 boys (aged 7 to 11 years) with either ADHD, CD, or ADHD + CD and 16 normal control children (NC) studied by means of a 2 (ADHD versus no ADHD) x 2 (CD versus no CD) design. We (1) tested whether similar or different patterns of cognitive, developmental risk, and psychosocial factors characterize the "pure" forms of the two disorders (i.e., ADHD and CD), and (2) compared the profile of the comorbid group (ADHD + CD) with those of the two pure groups. RESULTS: The ADHD group was significantly impaired on cognitive measures (inhibitory control and response alteration) and had greater delay in development and greater reading problems compared with CD and NC children; the CD group was exposed to significantly greater environmental adversity and had more severe problems in arithmetic than the ADHD and NC groups. The ADHD+CD group was similar to the ADHD group on cognitive, developmental, and reading measures and similar to the CD group on psychosocial and arithmetic measures. CONCLUSIONS: These results support the distinctiveness of ADHD and CD and the hypothesis that the comorbid condition of ADHD + CD is a hybrid of pure ADHD and pure CD. PMID- 7775361 TI - Six-year predictors of problems in a national sample: III. Transitions to young adult syndromes. AB - OBJECTIVE: To test developmental paths from adolescent syndromes and other candidate predictors to young adult syndromes. METHOD: A national sample assessed at ages 13 through 16 and 16 through 19 years was reassessed at 19 through 22 years in terms of six syndromes derived empirically from parent and self-reports, two syndromes derived only from parent reports, and one derived from self reports. RESULTS: Several young adult syndromes were similar to adolescent syndromes and were strongly predicted by these syndromes. A new syndrome designated as Shows Off and an adult Aggressive Behavior syndrome were both predicted by the adolescent Aggressive Behavior syndrome. This indicates a developmental transition away from overt aggression among some aggressive youths but not others. A syndrome designated as Irresponsible was predicted by the adolescent Attention Problems syndrome and may be an adult phenotype of attention deficit disorder. Surprisingly, attention problems were associated with more diverse problems among females than males. CONCLUSIONS: There are strong predictive relations from adolescent to adult syndromes. Sex differences in predictive paths argue against basing assumptions about both sexes on findings for one sex. PMID- 7775360 TI - Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. AB - OBJECTIVE: In the treatment of attention-deficit hyperactivity disorder (ADHD), the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants (methylphenidate and/or dextroamphetamine). However, the effectiveness of bupropion has been contrasted only with placebo. The primary aim of this study was to contrast the efficacy of bupropion with that of methylphenidate in the treatment of ADHD. METHOD: A double-blind, crossover design was used in this study. After a 14-day medication washout period, 15 ADHD subjects (7 to 17 years old) were randomized to either methylphenidate or bupropion for 6 weeks, washed out for an additional 2 weeks, and then "crossed over" to the other drug. Methylphenidate was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day (mean 0.7 mg/kg per day) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day (mean 3.3 mg/kg per day). RESULTS: Both methylphenidate and bupropion produced significantly greater (p < .001) and equivalent improvement on the Iowa-Conners Teacher's Rating Scale according to both the subjects' parents and teachers. The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale, Kagan's Matching Familiar Figures Test, Continuous Performance Test, Children's Depression Inventory, Children's Manifest Anxiety Scale, and Rey Auditory-Verbal Learning Test. CONCLUSIONS: In this double-blind, crossover trial, bupropion and methylphenidate were both effective and did not differ in their overall efficacy as treatments for ADHD. PMID- 7775362 TI - Models of adolescent psychopathology: childhood risk and the transition to adulthood. AB - OBJECTIVE: To examine the relationship between DSM-III disorder in adolescence (age 15 years) and DSM-III-R disorder in early adulthood (age 18 years), in relation to a history of behavior problems or disorder, other family and individual characteristics, and events commonly associated with the transition to adulthood. METHOD: The sample came from a New Zealand birth cohort selected from the general population. Data were obtained from ages 3 to 18 years for 890 of those enrolled. RESULTS: For both males and females, disorder at age 15 was strongly predicted by histories of early mental health problems. However, neither those histories, background characteristics, nor the experience of adolescent transition events modified the strength of association between disorder at ages 15 and 18 years. In childhood, after adjusting for histories of behavior problems, parental separations and (for boys) poor social competence remained independent predictors of disorder at age 15. Overall, boys appeared more vulnerable and those from socially disadvantaged backgrounds in early childhood had an elevated risk of disorder at age 18. After adjusting for disorder at age 15, adolescent unemployment remained an independent predictor of disorder at age 18 for both males and females. CONCLUSIONS: This study modeled the continuity of disorder across the adolescent transition period and, after taking earlier disorder into account, identified clear predictors of later disorder. This is the first step in the process of developing more effective interventions to reduce the risk of mental health disorders. PMID- 7775363 TI - Continuity and change of self-reported problem behaviors from adolescence into young adulthood. AB - OBJECTIVE: To investigate the 4-year course of behavioral and emotional problems from adolescence into young adulthood in a general population sample. METHOD: The population consisted of 364 individuals, aged 15 to 18 years at the beginning of the study. Subjects filled out the Youth Self-Report at the first time of assessment. At follow-up, 2 and 4 years later, subjects aged 19 or older completed the Young Adult Self-Report, which was derived from the Youth Self Report. RESULTS: Almost 40% of the adolescents who were classified as deviant initially were still deviant 4 years later. There was no significant difference in the continuity of internalizing problems versus externalizing problems in this sample. CONCLUSIONS: All types of problems tended to persist to a similar degree. This holds also for problems that are often regarded as typical childhood problems, such as attention problems and hyperactivity. Because adolescent problems are likely to continue, we need more knowledge on the efficacy of interventions. PMID- 7775364 TI - A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. AB - BACKGROUND: Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences, which may be of clinical relevance. METHOD: A randomized, double blind, parallel-group study of 6 weeks' duration comparing the efficacy and safety of sertraline (50-100 mg/day) with those of fluoxetine (20-40 mg/day) was conducted in 286 psychiatric outpatients with DSM-III-R major depression or bipolar disorder (depressed). Primary efficacy measurements consisted of the 17 item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. Secondary measurements included the Hamilton Rating Scale for Anxiety (HAM-A), the Raskin Depression Scale, the Covi Anxiety Scale, and the Leeds Sleep Questionnaire. Additionally, scores for two items and five factors from the HAM-D were analyzed. RESULTS: Efficacy was based on 124 evaluable patients in each treatment group. As measured by HAM-D and CGI-Severity scores, there was a significant (p < .001) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups. There was also no significant difference in the proportion of responders in each group. CGI-Improvement responder rates were 69% for sertraline and 67% for fluoxetine. Results of secondary efficacy measurements followed the same trend, although from the second week of treatment there was a numerical advantage (not statistically significant) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score. Headache and nausea were the most frequently reported events for both drugs. The incidence of early patient withdrawals due to treatment-emergent adverse events was 14% for sertraline and 13% for fluoxetine. The starting dosage (sertraline 50 mg/day, fluoxetine 20 mg/day) was the final dosage in 76% of patients in both treatment groups. CONCLUSION: Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety. PMID- 7775365 TI - A double-blind comparison of clomipramine and desipramine in the treatment of developmental stuttering. AB - BACKGROUND: Clomipramine, a serotonin reuptake blocker that has been shown to be effective in treating obsessive-compulsive disorder and other unwanted repetitive, ritualized behaviors, was hypothesized to be superior to desipramine, a tricyclic antidepressant with selective noradrenergic effects, for developmental stuttering. METHOD: Seventeen psychiatrically normal subjects, aged 14-61 years, with developmental stuttering completed a 10-week double-blind crossover trial of clomipramine and desipramine after a 2-week single-blind placebo phase. RESULTS: Clomipramine was superior to desipramine (two-tailed, p < .05) for 5 of 10 self-report ratings including stuttering severity on two scales, degree of preoccupation with stuttering and resistance to stuttering on a visual analog scale, and "expectancy" of stuttering on the Perceptions of Stuttering Inventory. CONCLUSION: Clomipramine may be clinically useful for some patients with developmental stuttering. Biological links between developmental stuttering and other repetitive motor patterns that are selectively responsive to serotonergic agents should be explored. PMID- 7775366 TI - Breastfeeding and sertraline: a 24-hour analysis. AB - BACKGROUND: Few reports exist on the levels of antidepressants in breast milk or on observed behavioral effects, if any, of neonates who are breast-fed. Thus, a dilemma exists for women who would like to breast-feed but require psychotropic medications. METHOD: Analysis of sertraline levels was performed on eight samples of breast milk obtained over a 24-hour period, after 3 weeks of breastfeeding, from a lactating patient taking sertraline and nortriptyline. During this same 24 hour period, two serum samples each were taken from mother and child for analysis of sertraline and nortriptyline levels. After 7 weeks of exclusive breastfeeding, an additional serum sample was obtained from mother and child for analysis of sertraline levels. Drug metabolites were not measured. RESULTS: Breast milk levels of sertraline were lowest 1 hour before the ingestion of sertraline and highest 5 to 9 hours after ingestion of the drug. The infant's serum sertraline and nortriptyline levels were nondetectable. CONCLUSION: These data indicate that sertraline levels in breast milk vary substantially over 24 hours and appear to be lowest within the 2 hours before and 1 hour after ingestion of the medication, with the peak probably occurring between Hours 1 and 9 postingestion. However, the absence of detectable serum sertraline and nortriptyline levels in the infant suggests that if either medication is present in infant serum, its concentration would be extremely low. No abnormal occurrences have been noted in the development of the infant. It would be important in future studies to measure metabolites in addition to medication levels since the former have been associated with untoward events in an infant. PMID- 7775367 TI - Phenomenology of intentional repetitive behaviors in obsessive-compulsive disorder and Tourette's disorder. AB - BACKGROUND: Recent evidence suggests that obsessive-compulsive disorder (OCD) and Tourette's disorder are related and have overlapping clinical features. The purpose of this study was to test the following hypotheses regarding intentional repetitive behaviors in these two disorders: (1) In OCD without comorbid Tourette's, they are preceded by cognitive phenomena and autonomic anxiety, but not sensory phenomena, and (2) in Tourette's without comorbid OCD, they are preceded by sensory phenomena, but not cognitive phenomena nor autonomic anxiety. METHOD: Fifteen adult OCD outpatients without tics and 17 adult Tourette's outpatients without OCD were evaluated with a structured interview. Questions assessed cognitive, sensory, and affective experiences related to intentional repetitive behaviors. RESULTS: Five of 17 Tourette's subjects were excluded because they had only unintentional or occasionally intentional tics. All OCD patients reported some cognitions preceding their intentional repetitive behaviors, whereas only 2 of 12 Tourette's patients reported cognitions. In comparison, all Tourette's patients reported sensory phenomena preceding repetitive behaviors, and none of the OCD patients reported such sensations. In addition, 13 OCD patients reported at least mild autonomic anxiety associated with their repetitive behaviors, whereas no Tourette's patients reported such symptoms. CONCLUSION: Intentional repetitive behaviors in OCD differ from those in Tourette's and are associated with cognitive and autonomic phenomena. Sensory phenomena preceded intentional repetitive behaviors in Tourette's but not in OCD patients. The dimensions examined in this study (cognition, sensory phenomena, and autonomic anxiety) may represent valid clinical factors for characterization of repetitive behaviors in OCD and Tourette's. PMID- 7775369 TI - Obsessive-compulsive spectrum disorders. PMID- 7775368 TI - Prescribing trends of antidepressants in bipolar depression. AB - BACKGROUND: This study utilizing pharmacoepidemiologic methods was undertaken to determine the prescribing patterns of antidepressants particularly in bipolar depression. METHOD: From pharmacy records of the McLean Hospital, the number of patients receiving antidepressants and given electroconvulsive therapy (ECT) from June 1, 1987, to May 8, 1993, was determined. We later linked these data bases with patients who were diagnosed with DSM-III-R bipolar depression (296.5) during the same period of time. RESULTS: During the 6-year period, it was determined that 3829 inpatients had received tricyclic antidepressants (TCAs), 2981 fluoxetine, 2603 trazodone, 809 bupropion, 743 monoamine oxidase inhibitors (MAOIs), 592 stimulants, 588 sertraline, 48 paroxetine, and 894 ECT. There were significant increases over time in prescriptions of MAOIs compared with fluoxetine (chi 2 = 14.36, p = .006), and bupropion compared with TCAs (chi 2 = 6.45, p = .04). There was a trend for bupropion to be prescribed more over time compared with fluoxetine (chi 2 = 5.09, p = .08). There were no significant changes in the prescribing of other antidepressants or in the use of ECT. CONCLUSION: At our center, prescribing of bupropion and MAOIs in bipolar depression has increased significantly. This may be related to the reports in the literature of the low switch rates to mania with the use of these drugs. PMID- 7775370 TI - Depressive personality disorder. PMID- 7775371 TI - Current concepts in schizophrenia: international symposia report new standards for assessment and treatment. Part II: Treatment issues and broadening options. PMID- 7775372 TI - Birth of the sliding filament concept in muscle contraction. AB - Why were the two classical papers by A.F. Huxley and R. Niedergerke and by H.E. Huxley and J. Hanson on the sliding filament concept in muscle contraction published in the same issue (May 22, 1954) of Nature? This historical survey reveals the background of the two groups' monumental work. PMID- 7775373 TI - Expression and characterization of Met92Gln mutant plastocyanin from Silene pratensis. AB - To investigate the role of the copper-ligand Met92 in the structural and functional properties of silene plastocyanin (PC), Met92 was replaced with Gln, which is the purposed fourth copper-ligand in another blue copper protein, stellacyanin. By use of the recently developed expression system [Hibino et al. (1994) J. Biochem. 116, 826-832], the Met92Gln mutant of intermediate precursor plastocyanin was successfully expressed in Escherichia coli and accumulated in the periplasmic space as a mature protein. In contrast to the wild type, most of the Met92Gln mutant PC accumulated as an apoprotein. After purification, mutant apoprotein could incorporate copper ions, although less efficiently than the wild type apoprotein. The absorption peak of Met92Gln mutant PC was blue-shifted from 597 nm in the wild type to 591 nm. The rhombic type EPR spectrum was obtained for the mutant in place of the axial spectrum in the wild type. Compared with that of the wild-type PC, the oxidation-reduction potentials of the Met92Gln mutant PC were lower by about 35 mV over the whole pH range examined. These results indicate that the Met92Gln mutant exhibited "stellacyanin-like" spectroscopic properties. Interestingly, the electron-transfer activities of the mutant PC with the physiological electron donor (cytochrome f) and acceptor (Photosystem I) were similar to that of the wild-type PC. Since Met92 is conserved in all the plastocyanins whose primary structures are known, we propose that the primarily function of Met as a copper-ligand is in the uptake of copper ions during folding rather than in electron-transfer activities. PMID- 7775374 TI - Determination of amounts of polyamines excreted in urine: demonstration of N1,N8 diacetylspermidine and N1,N12-diacetylspermine as components commonly occurring in normal human urine. AB - An analytical system developed for fractionating free and monoacetylated polyamines [Hiramatsu, K. et al. (1994) J. Biochem. 115, 584-589] was proved useful also in detecting diacetylpolyamines, namely N1,N8-diacetylspermidine (diAcSpd) and N1,N12-diacetylspermine (diAcSpm). Detection limits were 0.9 and 0.6 pmol (S/N = 5) for diAcSpd and diAcSpm, respectively. Analytical recovery and within-run variation were also satisfactory. Human urine samples were found to contain diAcSpd and diAcSpm. These polyamines were identified on the basis of the following observations: (i) their retention times were coincident with those of authentic samples; (ii) they were deacetylated to N8-acetylspermidine and monoacetyl- and free spermine, respectively, by acetylpolyamine amidohydrolase; and (iii) they were practically inert to direct oxidation by bacterial polyamine oxidase as were authentic samples. The amounts of eleven polyamine species including diAcSpd and diAcSpm in urine samples from 52 healthy persons were determined. Mean values for the major polyamine components were consistent with those reported by others. Although the amounts of diAcSpd and diAcSpm were very small, comprising only 1.4 and 0.46% of total polyamines, respectively, these two compounds were found to be always present in healthy human urine as regular constituents. Moreover, variation in their content among individuals was small, suggesting that excretion of these components in urine is strictly regulated. PMID- 7775375 TI - Geranylgeraniol is a potent inducer of apoptosis in tumor cells. AB - We screened various isoprenoids to find inducers of apoptosis for human leukemia HL-60 cells, and found that GGO (geranylgeraniol) had the most potent apoptosis inducing activity, as judged from DNA fragmentation in HL-60 cells. The apoptosis inducing activity of GGO is concentration- and time-dependent. DNA synthesis by HL-60 cells was selectively inhibited on treatment with GGO. Besides HL-60 cells, apoptosis was induced by GGO in various tumor cell lines, including human myeloid multipotential leukemia K562, lymphoblastic leukemia Molt3, and colon adenocarcinoma COLO320 DM. PMID- 7775376 TI - ATP-hydrolyzing excitation state of the reconstituted alpha 3 beta 3 complex of ATP synthase from the thermophilic bacterium PS3: structural characteristics shown by time-resolved small-angle X-ray scattering with synchrotron radiation. AB - The ATP-hydrolyzing excitation state of the alpha 3 beta 3 complex of the ATP synthase from the thermophilic bacterium PS3 was investigated using time-resolved small-angle X-ray scattering with synchrotron radiation. The results showed the presence of the alpha 3 beta 3 complex at a steady state during ATP hydrolysis when the alpha 3 beta 3 hexamer reacted with Mg-ATP. The radius of gyration of the complex in the steady state was significantly larger than that of the Mg-AMP PNP-hexamer complex, indicating a conformational change to an expanded structure during catalysis. This alpha 3 beta 3 complex dissociated into alpha 1 beta 1 heterodimers with apparent first-order reaction kinetics after all the ATPs were converted to ADPs. In contrast, when the alpha 3 beta 3 complex reacted with Mg ADP, the complex dissociated into dimers with apparent first-order reaction kinetics without showing the steady state of the complex. The dimers, however, re associated into the hexamer when Mg-ATP was added. The results were well explained by a computer simulation based on non-linear chemical dynamics, in which a reaction mechanism that incorporates the dynamic structure of the hexamer in the steady state was considered. PMID- 7775377 TI - Purification and properties of L-galactono-gamma-lactone dehydrogenase, a key enzyme for ascorbic acid biosynthesis, from sweet potato roots. AB - L-Galactono-gamma-lactone dehydrogenase (L-galactono-gamma lactone:ferricytochrome c oxidoreductase [EC 1.3.2.3], GLDHase) which catalyzes the terminal step in the biosynthesis of L-ascorbic acid (AsA) has been purified from roots of sweet potato (Ipomoea batatas L., cv. Kintoki). Highly purified preparation of the GLDHase was obtained by three column chromatography steps with a recovery of ca. 1%, after solubilization from mitochondria in sweet potato roots. SDS-PAGE exhibited a single band at 56 kDa. In the native state, the apparent molecular mass of the enzyme was 56 kDa, based on a Sephadex G-100 gel filtration. The pI and optimum pH values were 5.8 and 7.9, respectively. The Km value for L-galactono-gamma-lactone was 0.12 mM. Substrate inhibition was obtained at concentrations greater than 4.2 mM. The enzyme was inhibited by p chloromercuribenzoate (PCMB) and acriflavine, and the inhibition of acriflavine was diminished by the addition of FAD or FMN. The only effective substrate for the GLDHase was L-galactono-gamma-lactone. PMID- 7775378 TI - Enzyme properties of Aplysia ADP-ribosyl cyclase: comparison with NAD glycohydrolase of CD38 antigen. AB - An ecto-enzyme of NAD glycohydrolase (NADase) induced by retinoic acid in HL-60 cells is attributed to the molecule of CD38 antigen [Kontani, K., Nishina, H., Ohoka, Y., Takahashi, K., and Katada, T. (1993) J. Biol. Chem. 268, 16895-16898]. CD38 antigen has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase which generates cyclic adenosine diphosphoribose (cADPR) and nicotinamide (NA) from beta-NAD+. On the basis of this sequence homology, we compared enzyme properties between CD38 NADase expressed as a fusion protein in Escherichia coli and ADP-ribosyl cyclase purified from the ovotestis of Aplysia kurodai. 1) beta NAD+ analogs, nicotinamide 1, N6-ethenoadenine dinucleotide, and nicotinamide hypoxanthine dinucleotide, did not serve as good substrates for the ADP-ribosyl cyclase, suggesting that the intact adenine ring of beta-NAD+ was required for the cyclase-catalyzed reaction. On the other hand, CD38 NADase utilized the NAD analogs to form ADP-ribose and NA. 2) Kinetic analyses of the ADP-ribosyl cyclase reaction revealed that NA was first released from the substrate (beta-NAD+) enzyme complex, followed by the release of another product, cADPR, which was capable of interacting with the free enzyme. 3) The enzyme reaction catalyzed by the ADP-ribosyl cyclase was fully reversible; beta-NAD+ could be formed from cADPR and NA with a velocity similar to that observed in the degradation of beta NAD+. However, CD38 NADase did not catalyze the reverse reaction to form beta NAD+ from ADP-ribopase and NA. 4) The CD38 NADase activity was, but the ADP ribosyl cyclase activity was not, inhibited by dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775379 TI - Modulations of elastin expression and cell proliferation by retinoids in cultured vascular smooth muscle cells. AB - Effects of retinoid derivatives (retinol, retinal, retinoic acid, and etretinate) on elastin expression and cell proliferation in chick embryonic vascular smooth muscle cells were compared. Retinoic acid and etretinate inhibited cell proliferation to a greater extent than retinol and retinal. Retinol showed no significant effect on cell proliferation or elastin synthesis. Retinoic acid exhibited the most pronounced stimulatory effect on elastin synthesis with a maximum stimulation of 2.8-fold at the concentration of 10(-6) M for 24-48 h treatment. A comparable increase in elastin mRNA level was observed in the case of retinoic acid treatment. When the cells were serially passaged to the third subcultivation, elastin synthesis declined with increasing number of cell passages. Retinoic acid reversed this decline of elastin synthesis. The results indicate that retinoic acid was potentially active and retinol was inactive for both inhibition of cell proliferation and stimulation of elastin synthesis. The inhibitory activities of the four compounds for cell proliferation appear to parallel the stimulatory activities for elastin synthesis. The stimulation of elastin expression by retinoids may thus be closely related to the inhibition of cell proliferation. PMID- 7775380 TI - The mRNA for alpha 1(XIX) collagen chain, a new member of FACITs, contains a long unusual 3' untranslated region and displays many unique splicing variants. AB - We have isolated cDNAs and completed for the first time the primary structure for a novel collagenous chain that was partially characterized earlier and named alpha 1(Y) chain [Yoshioka, H. et al. (1992) Genomics 13, 884-886]. The size of the coding region was unexpectedly small compared with the length of the mRNA (> 10 kb), owing to the presence of a long 3' untranslated region (> 5 kb). The predicted polypeptide contained 1,142 amino acid residues with a 23-residue signal peptide consisting of 5 collagenous domains of 70-224 residues in length, interspersed and flanked with 6 noncollagenous (NC) domains. The primary structure is distinct from those of the 32 known collagen alpha-chains of types I through XVIII. Therefore, we designate this newly discovered collagen chain the alpha 1 chain of type XIX collagen. Sequence analysis suggested that this chain belongs to the recently discovered group of collagens known as FACITs (fibril associated collagens with interrupted triple-helices). Northern blotting analysis demonstrated hybridization of the cDNA to a large mRNA species (> 10 kb) extracted from a rhabdomyosarcoma cell line (CCL 136). We also isolated numerous truncated cDNA clones of which the 3' parts were different from the "proto" type of the mRNA of > 10-kb size. Sequence comparison between cDNAs and corresponding genomic DNA fragments indicated that unusual splicing events occurred through insufficient recognition at acceptor sites. Expression of the gene was extremely infrequent in the rhabdomyosarcoma cell line; it could be restricted to certain animal tissues both temporally and spatially during early development. PMID- 7775382 TI - Site-specific glycosylation of bovine butyrophilin. AB - Our previous studies showed that the N-linked sugar chains of most bovine glycoproteins from milk fat globule membranes (MFGM) contain the GalNAc beta 1- >4GlcNAc group [Sato et al. (1993) J. Biochem. 114, 890-900]. Since expression of the disaccharide structure is influenced by peptide sequences near the glycosylation sites [Smith and Baenziger (1992) Proc. Natl. Acad. Sci. USA 89, 329-333], the site-specificity of the N-acetylgalactosaminylated sugar chains was investigated using bovine butyrophilin, a major MFGM glycoprotein with known primary structure. Two glycopeptide fragments which contained the N-linked sugar chains linked to either Asn-55 or Asn-215 residue were obtained by digestion of the protein with Achromobacter protease I. The sugar chains released from each glycopeptide by hydrazinolysis were reduced with NaB3H4. Structural analyses of the oligosaccharides by sequential exoglycosidase digestion and methylation analysis revealed that only complex-type sugar chains with the GalNAc beta 1- >4GlcNAc structure are included in Asn-55-linked oligosaccharides, while only novel hybrid-type sugar chains detected previously in bovine MFGM glycoproteins are included in Asn-215-linked oligosaccharides. The results show that the glycosylation of butyrophilin occurs in a site-specific manner. PMID- 7775383 TI - Amino acid sequence of C-terminal 17 kDa CNBr-fragment of Akazara scallop troponin-I. AB - The M(r) 52,000 subunit of Akazara scallop striated muscle troponin, which was tentatively identified as troponin I, was cleaved into two major fragments with CNBr: C-terminal 17 kDa fragment (CN17K) and N-terminal 35 kDa fragment (CN35K) [J. Biochem. 108, 519-521 (1990)]. CN17K inhibits rabbit reconstituted actomyosin Mg-ATPase activity, weakly in the absence of troponin T but strongly in its presence, together with Akazara tropomyosin. CN35K, however, hardly shows such inhibition. Thus, the amino acid sequence of the CN17K was determined by the Edman method. CN17K comprises 135 amino acid residues and its calculated molecular mass is 15,732 Da. A computer search of the SWISS-PROT data base revealed the TnIs of crayfish tail muscle, rabbit skeletal muscle, and bovine cardiac muscle to be homologous proteins with total sequence homologies of 39, 30, and 30%, respectively, to CN17K. Significantly high homology was observed among these TnIs in the regions around residues 75-95, 99-114, and 135-151 of the rabbit TnI. From these facts, we conclude that the 52K subunit is a TnI. PMID- 7775381 TI - Cloning and characterization of cDNA for inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), a novel human plasma glycoprotein. AB - The cDNA encoding inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) was cloned from human liver cDNA libraries. Oligonucleotide primers of human liver cDNA for PCR were constructed from internal amino acid sequences obtained with proteolytic fragments of IHRP. The amplified cDNA served as a hybridization probe for the screening of human liver cDNA libraries. The cDNA of 2,977 bp contained an entire reading frame coding 930 amino acids. The N terminal 28 residues corresponded to a signal peptide for secretion. The N terminal 600 residues of the mature form exhibited considerable homology to those of ITI heavy chains, while the C-terminal 300 residues showed no homology with the heavy chains and low homology with ATP-dependent proteases. IHRP was readily cleaved into 85- and 35-kDa fragments when plasma was incubated at 37 degrees C. The cleaved site, Arg-Arg-Leu, was within a proline-rich region. Northern blot analysis of poly(A) RNAs from various human tissues only showed hybridization to liver RNA. PMID- 7775384 TI - Isolation and identification of adenosine triphosphoribosyl nicotinamide adenine dinucleotidephosphate from Azotobacter vinelandii. AB - A novel type of pyridine nucleotide, containing two adenosine triphosphate ribose residues rather than one, was isolated from Azotobacter vinelandii strain O. The nucleotide was shown to be 2"- or 3"-(2'-phosphoadenosine-5' diphosphoribosyl)nicotinamide adenine dinucleotide phosphate, in which 2'-phospho 5'-diphosphoadenosylribose was glycosidically linked to the NADP at position 2' or 3' of the nicotinamide mononucleotide moiety. The ATPribosylNADP did not show coenzyme activity for yeast glucose 6-phosphate dehydrogenase, nor was it cleaved by Neurospora crassa NAD(P) glycohydrolase, indicating that the biological properties conferred on the beta-NADP molecule were largely modified by the attachment of the ATP-ribose group. PMID- 7775385 TI - A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse. AB - To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression. PMID- 7775387 TI - The G-protein G(o) in mammalian cardiac muscle: localization and coupling to A1 adenosine receptors. AB - To investigate the functional relevance of the G-protein G(o) to adenosine induced effects in the heart, we studied the localization of G(o) and its interaction with A1 adenosine receptors. Concentrations of G(o) in various mammalian hearts differed markedly between the atrial and the ventricular muscle, as well as among species. In most species examined, the concentration of G(o) was much higher in the atrium than in the ventricle. The highest levels of G(o) in atria and ventricles were found in the ferret heart. An immunohistochemical study of the ferret heart with G(o) alpha-specific antibodies showed that G(o) was localized throughout the membranes of cardiac myocytes, including the intercalated disks. In addition, G(o) was densely distributed in the nerve fibers and Purkinje fibers. Analyses of G(o) alpha subtypes showed that bovine atrium mainly contained G(o)A alpha, while bovine ventricle contained only G(o)B alpha. By contrast, ferret ventricle contained both subtypes of G(o) alpha. To study the coupling of G(o) to A1 adenosine receptors, receptors in ventricular membranes of ferrets, which had been pretreated with pertussis toxin, or purified receptors were reconstituted with purified G(o)A and G(o)B. The reconstitution experiments indicated that both subtypes of G(o) coupled with A1 adenosine receptors. These results suggest that the effect of adenosine is mediated by both G(o)A and G(o)B in membranes of ferret cardiac myocytes. PMID- 7775386 TI - Binding mode of phospholipase A2 with a new type of phospholipid analog having an oxazolidinone ring. AB - Inhibition of phospholipases A2 (PLA2s) by a new type of monodispersed phospholipid analog, 3-dodecanoyl-4-phosphatidylcholinohydroxymethyl-2 oxazolidinone (oxazolidinone-PC), was investigated by the pH stat assay method using monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC) as the substrate. The PLA2s used were those from bovine pancreas and cobra (Naja naja atra) venom (Group I) and from Japanese mamushi (Agkistrodon halys blomhoffii) venom (Group II). This new-type substrate analog was shown to inhibit competitively both types of venom and bovine pancreatic enzymes by binding to the active site in a similar manner to the carboxamide-type analog 2-dodecanoyl-amino 1-hexanol-phosphocholine (amide-PC). The binding of a stereoisomer, (R)-amide-PC, to N. naja atra (Group I) and A. halys blomhoffii (Group II) PLA2s was facilitated by the binding of Ca2+ to the enzymes. On the other hand, the binding of (R)-oxazolidinone-PC to the N. naja atra (Group I) enzyme was found to be independent of Ca2+ binding, while its binding to the A. halys blomhoffii (Group II) enzyme was markedly facilitated by the binding of Ca2+ to the enzyme. The binding of (R)-amide-PC to N. naja atra PLA2 (Group I) was markedly influenced by the ionization state of the catalytic residue His 48, whereas the binding of (R) oxazolidinone-PC was found to be practically independent of the ionization state of this residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775388 TI - Clustering of Sp1 sites near the promoter region of ICP34.5 in herpes simplex virus type 1. AB - We report that a host nuclear protein of approximately 100 kDa binds to the tandemly reiterated DR2 sequence of herpes simplex virus type 1 (HSV-1). The DR2 sequence is a repeated component in the "a" sequence, which defines the signals for cleavage and encapsidation of viral DNA; the "a" sequence also contains the promoter regulatory signals for the gene encoding the viral neurovirulence factor, ICP34.5. Characterization of the host binding protein by means of gel shifts and DNase I footprinting revealed this protein is the eukaryotic transcription factor, Sp1. Furthermore, as judged from the sequence homology, the DR2 region contains clustered matches to the consensus binding site for Sp1. Comparison of the host factor and purified Sp1 (by means of gel shifts and footprinting) confirmed these findings. Since clustered DNA recognition elements represent unusually high affinity binding sites, these repeated Sp1 motifs proximal to the ICP34.5 gene suggest that this region may be a major Sp1 binding site in the viral genome. PMID- 7775389 TI - Involvement of pertussis toxin-sensitive mechanism in retinoic acid-induced differentiation of human leukemic HL-60 cells. AB - Retinoic acid-induced differentiation of human leukemic HL-60 cells is accompanied with the early induction of an ecto-enzyme of NAD+ glycohydrolase (NADase), which has recently been identified as human leukocyte cell surface antigen CD38 [Kontani, K. et al. (1993) J. Biol. Chem. 268, 16895-16898]. The terminal cell differentiation attendant upon the cell growth arrest was, but the early induction of CD38 NADase activity was not, inhibited by prior treatment of HL-60 cells with pertussis toxin, which catalyzed ADP-ribosylation of the membrane-bound alpha beta gamma-trimeric GTP-binding proteins. The prior treatment was, however, not essential for the toxin-induced inhibition of the cell differentiation; the inhibition by the addition of pertussis toxin was still observed even after retinoic acid-induced expression of CD38 antigen. This suggested that a pertussis toxin-sensitive mechanism was involved in a late process of cell differentiation. Indeed, HL-60 cells appeared to secrete a differentiation-supporting factor in response to retinoic acid, since the cell differentiation was accelerated and potentiated upon culture of the cells in a conditioned medium prepared from retinoic acid-treated cells. The action of the differentiation-supporting factor was destroyed by heating and markedly attenuated in pertussis toxin-pretreated HL-60 cells. Thus, the whole process of the retinoic acid-induced cell differentiation appeared to consist of two distinguishable periods in terms of sensitivity to pertussis toxin; the toxin insensitive early period characterized by the induction of CD38 NADase activity and the toxin-sensitive late period in which the secretion of a differentiation supporting factor might be involved. PMID- 7775390 TI - Localization of three fragments of connectin in chicken breast muscle sarcomeres. AB - Connectin (titin) links the Z line to the myosin filament in sarcomeres of vertebrate skeletal muscle. An 800 kDa fragment of alpha-connectin runs from the Z line up to the N2 line region in the I band, and the following beta-connectin portion runs up to the edge of the M line on the myosin filament in chicken breast muscle sarcomeres. Immunoelectron microscopy showed that a 400 kDa fragment following the 800 kDa fragment reaches the edge of the myosin filament and, thereafter a 1,700 kDa fragment runs to the M line on the myosin filament in chicken breast muscle sarcomeres. When stretched, the epitopes to anti-400 kDa fragment antibodies outside the myosin filament moved toward the inside of the I band. PMID- 7775391 TI - Purification and characterization of protein disulfide isomerase from soybean. AB - Protein disulfide isomerase (PDI), which catalyses the folding of newly synthesized or denatured proteins through correct disulfide formation, was purified from soybean (Glycine max). The enzyme was purified 12,000-fold over crude extracts to apparent homogeneity in six purification steps: 60-70% ammonium sulfate fractionation, and chromatography on DEAE Toyopearl 650M, Q-Sepharose Fast Flow, Hiload Superdex 200 pg, Phenyl Sepharose HP, and TSK G-3000 SW. The native enzyme had a molecular weight of 120 kDa on gel filtration. Subunit molecular weight was estimated as 63 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis, thus indicating the enzyme to be comprised of two identical subunits. The enzyme pH optimum was 8.0 with reactivation of scrambled RNase, and the pI 7.65. The N-terminal amino acid sequence of soybean PDI was homologous to that of mature alfalfa as deduced from the cDNA sequence. Two identical active site sequences, APWCGHCK, were obtained from different proteolytic peptide fragments of soybean PDI. Soybean PDI facilitated reactivation not only of scrambled RNase, but denatured and reduced lysozyme and the Bowman Birk soybean trypsin inhibitor as well. This is the first report to appear on the the purification, characterization and amino acid sequence analysis of the active site of a plant PDI. PMID- 7775393 TI - Protein kinase C phosphorylates p50 LSP1 and induces translocation of p50 LSP1 in T lymphocytes. AB - A lymphocyte-specific protein, p50, is phosphorylated on Ser and Thr residues in mitogen-activated T cells, suggesting that this molecule plays some role in the T cell activation cascade. p50 was identified as lymphocyte specific protein 1 (LSP1), which is a putative calcium-binding protein. In the present study, to clarify the role of p50 protein in the cascade, in vivo and in vitro phosphorylation of this molecule, and the effect of the phosphorylation on its distribution in activated T cells were examined. First, to obtain a sufficient amount of p50 as a phosphorylation substrate, p50 cDNA, which encodes a protein of 330 amino acid residues with a molecular mass of 36,728 Da, was cloned from an ICR mouse thymocyte cDNA library and expressed in Escherichia coli. When the putative coding region of p50 cDNA was expressed in E. coli, the product showed an apparent molecular mass of 50 kDa on SDS-PAGE. The recombinant p50 was phosphorylated in vitro by rabbit protein kinase C (PKC) and by murine cytosolic protein kinase, that was activated by a combination of phosphatidylserine and diacylglycerol. Furthermore, p50 was shown to be phosphorylated on the same sites in T cells upon stimulation with Con A as when phosphorylated in vitro by rabbit PKC, indicating that p50 is phosphorylated by PKC in Con A-stimulated T cells. On subcellular fractionation followed by immunoblotting analysis, membrane-bound p50 was shown to be released from the membrane following activation of PKC in T cells. These results and the recent finding that p50 binds to actin fibers raise the possibility that p50 controls the binding of actin fibers to the plasma membrane under regulation by PKC in T cells. PMID- 7775392 TI - Mouse macrophage metalloelastase expressed in bacteria absolutely requires zinc for activity. AB - Mouse macrophage metalloelastase was expressed in Escherichia coli. This recombinant enzyme (rMME) was present in the inclusion bodies that were solubilized in 7 M guanidine HCl. After removal of guanidine HCl, rMME was purified with a Q-Sepharose column. Degradation of [3H]elastin by rMME absolutely required Ca2+; the optimal Ca2+ concentration was 5 mM. NaCl stimulated the enzyme activity; maximal stimulation was obtained at 400 mM. The rMME activity was inhibited by metalloprotease inhibitors, but not by serine, aspartyl, or thiol protease inhibitors. Among the divalent cations tested, only Ba2+ and Sr2+ exhibited marginal stimulation of rMME activity in the absence of Ca2+. Cu2+, Zn2+, or Cd2+ strongly inhibited rMME activity with IC50 values between 68 and 180 microM, while Mg2+, Ba2+, Mn2+, Co2+, and Sr2+ had no effect. The requirement of Zn2+ for rMME activity was determined. Significant enzyme activity was present in rMME treated with EDTA followed by Q-Sepharose column chromatography. Only when the inclusion bodies were solubilized in the presence of 20 mM EDTA, did an enzyme preparation which was absolutely dependent on exogenous Zn2+ for activity result. The optimal Zn2+ concentration for rMME activation was 100 microM. These results indicate that Zn2+ is tightly bound to rMME. PMID- 7775394 TI - Specific aminoacylation of C4N hairpin RNAs with the cognate aminoacyl-adenylates in the presence of a dipeptide: origin of the genetic code. AB - A series of C4N hairpin RNAs bearing anticodon nucleotides at the 5' ends and a discriminator base and the sequence CCA at the 3' ends was constructed by an in vitro transcription system using T7 RNA polymerase. These RNAs were aminoacylated specifically with their cognate amino acids by reaction with aminoacyl-adenylates in the presence of a dipeptide, valyl-aspartic acid, suggesting that such hairpin RNAs are able to play the role of the present-day tRNA and that valyl-aspartic acid can perform the function of the present-day aminoacyl-tRNA synthetase as a catalyst in the aminoacylation reaction. These results should provide a useful clue to elucidating the origin of the genetic code. PMID- 7775395 TI - Role of Lys108 in the enzymatic activity of RNase Rh from Rhizopus niveus. AB - In order to elucidate on the mechanism of action of RNase Rh from Rhizopus niveus, we investigated the role of Lys108, which is conserved among the RNase T2 family RNases except for two cases. The RNase activities of Lys108 mutant RNases, RNase RNAP K108R and K108L, are about 33.5 and 3.1% of that of the wild type enzyme, respectively. The relative rates of cleavage of dinucleoside phosphates by these two mutant enzymes were comparable to those with RNA as a substrate. The kinetic parameters of RNases RNAP K108R and K108L towards XpGs (where X is one of A, G, U, and C) were measured. The data indicated that the Km values of the two mutant enzymes are similar to those of the wild-type enzyme. The rates of release of the four nucleotides from RNA by digestion with the mutant enzymes were in the order A > G > U > C, which is qualitatively the same as that of the wild-type enzyme. From these data, we concluded that the Lys108 residue participates in the catalytic process, but not in the binding, and the positive charge of Lys108 is indispensable for the catalytic process, that is, the positive charge of Lys108 may stabilize the pentacoordinated intermediate in the transition state as proposed in the case of Lys41 in RNase A, or may polarize the phosphate moiety of the substrate. PMID- 7775396 TI - Kinetic analysis of endocytosis and intracellular fate of liposomes in single macrophages. AB - Endocytosis and the intracellular fate of liposomes in single mouse peritoneal macrophages were examined kinetically by fluorescence microphotometry. Liposomes labeled with N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine or containing 8-amino-naphthalene-1,3,6-trisulfonate were promptly incorporated into macrophages on incubation at 37 degrees C, but fluorescence increase caused by hydrolysis of 4-methylumbelliferyl-beta-D-glucoside encapsulated in the liposomes was observed after 30 min of incubation. The fluorescences of calcein and 8 hydroxy-1,3,6-pyrenetrisulfonate (HPTS) in liposomes, which were respectively quenched statically due to high concentration and dynamically by a co-entrapped fluorescence quencher, p-xylene-bis-pyridinium bromide, also increased from 30 min after the start of liposome incorporation, indicating that macrophages require this period for intracellular delivery of liposomes from the cell surface to lysosomes. Measurement of the intraendosomal pH change in a single macrophage at 37 degrees C with liposomes containing a pH-sensitive fluorescent marker, HPTS, showed that the pH value decreased continuously to a constant value of 5.5 in 30-40 min after endocytosis, and this decrease was reversed on addition of NH4Cl, suggesting that acidification of endosomes is not a stepwise reaction and is coupled with delivery of liposomes. These fluorescence microphotometric systems using liposomes containing different fluorescent dyes should be useful for kinetic analyses of the endocytosis and intracellular fate of liposomes in various phagocytes. PMID- 7775398 TI - Purification and molecular shape of a 144 kDa protein bearing N-acetylglucosamine residues from rat liver nuclear envelopes. AB - A 144 kDa protein was purified from the WGA-Sepharose bound fraction of a rat liver nuclear envelope salt-extract by hydroxyapatite HPLC (HAP HPLC). Two other, 120 and 86 kDa, proteins were also partially purified from the fraction by a combination of DEAE- and HAP-HPLCs. It was suggested that the 144, 120, and 86 kDa proteins bear GlcNAc residues, and are nucleoporins, because they were purified from nuclear envelopes, reacted with WGA-HRP, and cross-reacted with an antibody against p62 nucleoporin complexes. The sedimentation coefficients and Stokes' radii of these GlcNAc-bearing proteins were determined by glycerol density gradient centrifugation and gel filtration in the presence of 500 mM NaCl. The molecular masses calculated from these values suggested that these three proteins each exist as a monomer under the conditions employed. The axial ratios of the purified 144, 120, and 86 kDa GlcNAc-proteins were estimated to be 35, 31, and 31, respectively. These values suggested that they are rod-shaped molecules. The axial ratio of a purified nucleoporin-complex consisting of 62, 60, and 54 kDa components bearing GlcNAc was shown to be 20. This nucleoporin complex seems to be a rod-shaped complex. From these results, a rod shape is proposed to be a common characteristic of GlcNAc-proteins in nuclear envelopes. PMID- 7775397 TI - Apparent antibacterial activity of catalase: role of lipid hydroperoxide contamination. AB - Escherichia coli was killed by catalase in dose-, time-, and pH-dependent manners. Dialyzed catalase had bactericidal activity, but enzyme which had been heat-denatured or inactivated by pretreatment with 3-aminotriazole plus hydrogen peroxide did not. Cytochrome c and hemoglobin also had bactericidal activity. Thiobarbituric acid-reactive substances were detected in commercial hemoproteins except for horseradish peroxidase and the relationship between the contents of these substances and bactericidal activity was demonstrated. Without the addition of hydroperoxide, hemoproteins except for horseradish peroxidase initiated the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and catalase caused the peroxidation of linoleic acid. The pH patterns of bactericidal activity, lipid peroxidation, and the oxidation of ABTS were similar. The results indicate that hemoprotein preparations are contaminated with lipid hydroperoxides and it is the decomposition of these contaminants catalyzed by the hemoprotein into alkoxyl/peroxyl radicals that causes bacterial killing. PMID- 7775399 TI - Palmitoyl lysozyme-induced stabilization of PE (phosphatidylethanolamine) liposomes and their interaction with Candida albicans. AB - The interaction with fungal cells of dioleoylphosphatidylethanolamine liposomes coated with palmitoyl lysozyme was investigated using lysozyme as a stabilizer for an unstable bilayer as well as a recognizer for a specific target cell. Lysozyme, which interacts with chitin in the fungal cell wall, lyses chitin and kills the cells, was acylated with N-hydroxysuccinimide ester of palmitic acid (NHSP) and incorporated into the lipid bilayer. Lysozyme was optimally modified when the ratio of NHSP to lysozyme was 15 at pH 8.0. Modification of lysozyme was detected by SDS-PAGE, and its molecular weight was about 1,500 greater than that of the intact lysozyme at the optimal ratio of NHSP to lysozyme. The activity of palmitoyl lysozyme toward glycolchitin was reduced to 35% of that of intact lysozyme. Both lysozyme and palmitoyl lysozyme had antifungal activities, but palmitoyl lysozyme was more effective than intact lysozyme against Candida albicans. The minimal molar ratio of palmitoyl lysozyme to phosphatidylethanolamine required to form stable liposomes was 2.4 x 10(-4), and the optimal ratio was about 2.4 x 10(-3). The percentage survival of cells treated with the inserted palmitoyl lysozyme was lower than that of cells treated with free palmitoyl lysozyme. These findings suggest that palmitoyl lysozyme incorporated liposomal membrane is more effectively adsorbed by Candida albicans than free palmitoyl lysozyme is. PMID- 7775400 TI - Role of the C-terminal region of beta-amylase from barley. AB - To investigate the role of the C-terminal region of barley beta-amylase, plasmid delta 54 was constructed with an expression vector (pBETA92) of barley beta amylase by site-directed mutagenesis. Escherichia coli JM109 harboring plasmid delta 54 was expected to express delta 54 beta-amylase in which 54 amino acid residues were deleted from the C-terminus. The enzyme production started in the logarithmic phase, increased linearly, and reached a maximum after 12 h. delta 54 beta-amylase gave a single activity band on isoelectric focusing (pI 6.85). delta 54 beta-amylase was purified from the cells by consecutive alpha cyclodextrin/Sepharose 6B column chromatography. A comparison of the properties of the mutant enzyme with those of the original recombinant beta-amylase [Biosci. Biotech. Biochem. (1994) 58, 1080-1086] revealed two major differences. First, the original recombinant beta-amylase showed heterogeneity on isoelectric focusing, but delta 54 beta-amylase gave a single main band of protein (pI 6.85). Therefore, the isoelectrophoretic heterogeneity of the original recombinant beta amylase was apparently due to its C-terminal region. Secondly, delta 54 beta amylase lacked thermostability. Therefore, it was concluded that the C-terminal region was significantly involved in the thermostability of beta-amylase. PMID- 7775401 TI - A novel proteinase, glucagon-degrading enzyme, secreted by a human pancreatic cancer cell line, HPC-YO. AB - Sixty-four kinds of cell lines were examined as to their ability to degrade glucagon using conditioned-media obtained from their protein-free cultures. Two human tumor cell lines were shown to produce this activity, and the cell line, HPC-YO, established from a human pancreatic carcinoma was shown to produce the highest level of activity. The glucagon-degrading enzyme (GDE) was purified from HPC-YO conditioned-medium by a combination of ion-exchange, gel filtration, and hydroxylapatite column chromatographies. The purified GDE also degraded vasoactive intestinal polypeptide (VIP) and secretin, however, it did not cleave EGF, gastrin, insulin, somatostatin, substance P, neurotensin, or growth hormone. The molecular weight of GDE is 83,000, as determined on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of GDE was blocked, and the five partial amino acid sequences obtained on lysyl-endopeptidase digestion were determined to be N-L-T-E-E-Y-D-V-S-D-G-E-I-E-L-L-Y-E-K, V-E-T-Y-Y-D-L-L-F-E-K, L Y-W-F-L-D-E-A-K, S-N-S-T-S-Y-V-K, and Y-Y-A-S-T-S-Y-D-D-T-Y-K. The same or homologous amino acid sequences have not been found in known proteins, demonstrating that GDE is a novel peptidase that degrades the secretin family: glucagon, VIP, and secretin. PMID- 7775402 TI - Expression of differentiation-related phenotypes and apoptosis are independently regulated during myeloid cell differentiation. AB - When human promyelocytic leukemia cell line HL-60 was treated with various differentiation-inducers, apoptosis always occurred after the full appearance of differentiation-related phenotypes. However, the two phenomena could be dissociated when HL-60 cells were treated with PDBu. When HL-60 cells were cultured with PDBu for more than 36 h, apoptosis was induced following differentiation. Apoptosis was not, however, observed when PDBu was removed within 24 h, even though induction of differentiation-related phenotypes, such as NBT-reducing ability and surface marker expression, was the same as that in the control. Northern blot analysis revealed that bcl-2 mRNA was rapidly down regulated within 6 h of the treatment with PDBu. The amount of bcl-2 mRNA recovered to that of undifferentiated HL-60 cells when PDBu was washed out within 24 h. In contrast, the recovery of bcl-2 was incomplete when the cells were treated with PDBu for more than 36 h, suggesting that bcl-2 is also a critical regulator of the cell fate during myeloid differentiation. This hypothesis was confirmed by experiments using antisense oligonucleotides, i.e., blocking the recovery of bcl-2 mRNA by antisense oligonucleotides could result in the induction of apoptosis in HL-60 cells from which PDBu was removed within 24 h. Moreover, overexpression of BCL-2 in HL-60 cells could block apoptosis during differentiation without any significant effect on differentiation itself. These results strongly suggest that apoptosis is not a simple consequence of differentiation-induction, and that apoptosis and differentiation are regulated independently in myeloid cells. PMID- 7775403 TI - Preparation and characterization of calmodulin-dependent protein kinase IV (CaM kinase IV) free of CaM-kinase IV kinase from rat cerebral cortex. AB - Our earlier finding [Kameshita, I. and Fujisawa, H. (1993) J. Biochem. 113, 583 590] that calmodulin-dependent protein kinase IV (CaM-kinase IV) from rat cerebral cortex is markedly activated through autophosphorylation was reexamined in the light of a more recent study [Okuno, S. and Fujisawa, H. (1993) J. Biochem. 114, 167-170] suggesting the involvement of Ca2+/calmodulin-dependent CaM-kinase IV kinase in the activation of CaM-kinase IV in rat brain. Further purification of the previous CaM-kinase IV preparation by HPLC on a DEAE-NPR column abolished its marked activation on incubation under Ca2+/calmodulin dependent phosphorylation conditions, and the marked activation was restored by the addition of the fraction separated on a DEAE-NPR column, suggesting that CaM kinase IV was separated from CaM-kinase IV kinase involved in its activation by HPLC on DEAE-NPR. The HPLC-purified CaM-kinase IV still underwent a slow autophosphorylation, which was an intramolecular reaction. Some kinetic properties of CaM-kinase IV before and after autophosphorylation were examined for comparison. In addition, the purification by HPLC on DEAE-NPR revealed that a novel Ca(2+)-dependent calmodulin-binding protein, designated as CaMBP64, is present as a major contaminant in the previous purified CaM-kinase IV preparation. PMID- 7775404 TI - Analysis of functional domains of a GC box-binding protein, BTEB. AB - BTEB is a small GC box-binding protein containing three contiguous zinc finger structures in the C-terminal region of the molecule, and activates or represses the transcription of genes with the GC box sequence in the promoter, depending on the repetitiveness of the GC box sequence [Imataka et al. (1992) EMBO J. 11, 3663 3671]. We have analyzed functional domains of BTEB in a transient expression system using Y-1 cells (a mouse adrenal cortex cell line). BTEB contained two regions responsible for the transcriptional activation. These regions showed a sequence similarity to each other and appeared to enhance the transcription independently. The two sequences were rich in hydrophobic amino acids and showed no similarity to the sequences of transactivation domains so far elucidated. The DNA-binding properties of BTEB were also analyzed by means of the gel mobility shift assay. Three contiguous zinc finger motifs were needed for the binding activity. Furthermore, it was revealed that a short basic region immediately N terminal to the zinc finger motifs was required for the DNA binding. PMID- 7775405 TI - Chronic administration of beta-adrenergic agonists can mimic the stimulative effect of cold exposure on protein synthesis in rat brown adipose tissue. AB - When mammals are exposed to a cold environment for a long time, the capacity of nonshivering thermogenesis by brown adipose tissue (BAT) increases in association with the stimulation of synthesis of some specific proteins and tissue hyperplasia, which are totally dependent on sympathetic innervation to this tissue. To clarify the roles of the adrenergic mechanisms for the cold-induced protein synthesis and hyperplasia in BAT, in this study, the effects of chronic treatment with adrenergic agonists using an osmotic mini-pump were examined in rats. Continuous administration of noradrenaline or isoproterenol (beta-agonist) for 10 days resulted in increased synthesis of the mitochondrial uncoupling protein and an isoform of glucose transporter (GLUT4), and tissue hyperplasia, in the same way as after cold exposure of the same duration. Phenylephrine (alpha agonist) administration did not have any significant effect. Surgical sympathetic denervation completely abolished the effects of cold exposure, whereas it did not influence those of adrenergic agonists at all. These results indicate that the stimulative effects of cold exposure on protein synthesis and hyperplasia of BAT are attributable solely to the beta-adrenergic action of noradrenaline secreted from the sympathetic nerves in this tissue. PMID- 7775406 TI - Oligonucleotides as research, diagnostic, and therapeutic agents. PMID- 7775407 TI - Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. AB - The mitogen-activated protein kinase (MAP kinase) pathway is thought to play an important role in the actions of neurotrophins. A small molecule inhibitor of the upstream kinase activator of MAP kinase, MAP kinase kinase (MEK) was examined for its effect on the cellular action of nerve growth factor (NGF) in PC-12 pheochromocytoma cells. PD98059 selectively blocks the activity of MEK, inhibiting both the phosphorylation and activation of MAP kinases in vitro. Pretreatment of PC-12 cells with the compound completely blocked the 4-fold increase in MAP kinase activity produced by NGF. Half-maximal inhibition was observed at 2 microM PD98059, with maximal effects at 10-100 microM. The tyrosine phosphorylation of immunoprecipitated MAP kinase was also completely blocked by the compound. In contrast, the compound was without effect on NGF-dependent tyrosine phosphorylation of the pp140trk receptor or its substrate Shc and did not block NGF-dependent activation of phosphatidylinositol 3'-kinase. However, PD98059 completely blocked NGF-induced neurite formation in these cells without altering cell viability. These data indicate that the MAP kinase pathway is absolutely required for NGF-induced neuronal differentiation in PC-12 cells. PMID- 7775408 TI - DNA enzymology above 100 degrees C. Topoisomerase V unlinks circular DNA at 80 122 degrees C. AB - The widespread application of polymerase chain reaction and related techniques in biology and medicine has led to a heightened interest in thermophilic enzymes of DNA metabolism. Some of these enzymes are stable for hours at 100 degrees C, but no enzymatic activity on duplex DNA at temperatures above 100 degrees C has so far been demonstrated. Recently, we isolated topoisomerase V from the hyperthermophile Methanopyrus kandleri, which grows up to 110 degrees C. This novel enzyme is similar to eukaryotic topoisomerase I and acts on duplex DNA regions. We now show that topoisomerase V catalyzes the unlinking of double stranded circular DNA at temperatures up to 122 degrees C. In this in vitro system, maximal DNA unlinking occurs at 108 degrees C and corresponds to complementary strands being linked at most once. These results further imply that in the presence of sufficient positive supercoiling DNA can exist as a double helix even at 122 degrees C. PMID- 7775409 TI - Primary structure and functional expression of a cDNA encoding the bile canalicular, purine-specific Na(+)-nucleoside cotransporter. AB - We previously characterized a purine-specific Na(+)-nucleoside cotransport system in bile canalicular membrane. The function of this transport system may be related to conserving nucleosides and preventing cholestasis. We report here the isolation of a cDNA encoding a Na(+)-dependent nucleoside transporter from rat liver using an expression cloning strategy. The substrate specificities and kinetic characteristics of the cloned cotransporter are consistent with the properties of the Na(+)-dependent, purine-selective nucleoside transporter in bile canalicular membranes. The nucleotide sequence predicts a protein of 659 amino acids (72 kDa) with 14 putative membrane-spanning domains. Northern blot analysis showed that the transcripts are present in liver and several other tissues. Data base searches indicate significant sequence similarity to the pyrimidine-selective nucleoside transporter (cNT1) of rat jejunum. Although these two subtypes of Na(+)-nucleoside cotransporter have different substrate specificities and tissue localizations, they are members of a single gene family. PMID- 7775410 TI - Evidence for involvement of phosphatidylcholine-phospholipase C and protein kinase C in transforming growth factor-beta signaling. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that elicits a wide variety of responses in cells. TGF-beta binds to cell surface receptors that contain cytoplasmic serine/threonine kinase domains. Here we provide evidence that both phospholipase C and protein kinase C (PKC) are involved in the TGF-beta activation of transcription and luciferase expression from the p3TP-Lux plasmid. Down-regulation of PKC prevents TGF-beta 1 induction of luciferase expression. Staurosporin and Calphostin C, inhibitors of PKC, block the ability of TGF-beta 1 to initiate transcription of the luciferase gene. Further, D609, an inhibitor of phosphatidylcholine-phospholipase C (PC-PLC), and secondarily PKC also blocks TGF-beta 1-induced transcription of the transgene in A549 cells while the phosphatidylinositol-PLC pathway inhibitor U73122 is without effect. TGF-beta elevates steady-state mRNA levels for the endogenous PAI-1 and fibronectin genes. Treatment of cells with calphostin C or D609 prevents the TGF beta-induced increase in these mRNAs. Together, these results suggest that PC-PLC and PKC are in a TGF-beta signaling pathway that results in elevated gene expression. PMID- 7775412 TI - Cloning and expression of an evolutionary conserved single-domain angiotensin converting enzyme from Drosophila melanogaster. AB - Mammalian somatic angiotensin converting enzyme (EC 3.4.15.1, ACE) consists of two highly homologous (N- and C-) domains encoded by a duplicated gene. We have identified an apparent single-domain (67 kDa) insect angiotensin converting enzyme (AnCE) in embryos of Drosophila melanogaster which converts angiotensin I to angiotensin II (Km, 365 microM), removes Phe-Arg from the C terminus of bradykinin (Km, 22 microM), and is inhibited by ACE inhibitors, captopril (IC50 = 1.1 x 10(-9) M) and trandolaprilat (IC50 = 1.6 x 10(-8) M). We also report the cloning and expression of a Drosophila AnCE cDNA which codes for a single-domain 615-amino acid protein with a predicted 17-amino acid signal peptide and regions with high levels of homology to both the N- and C-domains of mammalian somatic ACE, especially around the active site consensus sequence. Northern analysis identified a single 2.1-kilobase mRNA in Drosophila embryos, and Southern analysis of Drosophila genomic DNA indicates that the insect gene is not duplicated. When expressed in COS-7 cells, the AnCE protein is a secreted enzyme, which converts angiotensin I to angiotensin II and is inhibited by captopril (IC50 = 5.6 x 10(-9) M) and trandolaprilat (IC50 = 2 x 10(-8) M). The evolutionary significance of these results is discussed. PMID- 7775411 TI - A spectroelectrochemical method for differentiation of steric and electronic effects in hemoglobins and myoglobins. AB - Spectroelectrochemical techniques are described which enable us to compare anion effects on redox curves of structurally distinct hemoglobins with oxygenation curves obtained under equivalent conditions. Nernst plots for tetrameric vertebrate Hbs show evidence of cooperativity, with the T state conformation more resistant to oxidation than the R state. Anions shift the conformation toward the T state and decrease the ease of oxidation, with variations in anion sensitivity similar to those observed in oxygen equilibria. Oxygen binding, unlike electron exchange, is known to be subject to steric constraints that vary considerably in natural and engineered hemoglobins that have differences in the distal residues of the heme pocket. Since oxidation curves are not subject to steric hindrance, anion-induced differences between the oxidation and oxygenation curves can be indicative of anion-induced alterations in the stereochemistry of the heme pocket that alters the ease of ligand entry or exit. Addition of inositol hexaphosphate to solutions of Hb A in 0.2 M nitrate generates such differences: the ease of electron abstraction from deoxy (T state) Hb A is unaffected, while, as previously reported, the oxygenation of deoxy (T state) Hb A is greatly hindered. The difference between inositol hexaphosphate effects on initial stages of oxidation and oxygenation indicates that the explanation for "multiple T states" in oxygen binding lies in the ability of the polyanion to greatly increase steric hindrance to ligand entry, without appreciable changes in the electronic features of the heme environment. PMID- 7775414 TI - Triacylglycerol synthesis by purified triacylglycerol synthetase of rat intestinal mucosa. Role of acyl-CoA acyltransferase. AB - The activities of the proposed triacylglycerol synthetase complex, acyl-CoA ligase, acyl-CoA acyltransferase (AAT), monoacylglycerol acyltransferase (MGAT), and diacylglycerol acyltransferase (DGAT), coeluted upon Cibacron blue 3GA agarose affinity chromatography of detergent-solubilized rat intestinal microsomes. The AAT activity is associated with a 54-kDa protein, that binds covalently an acyl group from acyl-CoA via a thiol ester linkage (Lehner, R. and Kuksis, A. (1993) J. Biol. Chem. 268, 24726-24733). Reagents that prevent the acyl-AAT formation inhibit triacylglycerol synthesis as does the removal of AAT from the complex by immunoprecipitation. In the absence of mono- and diacylglycerol acceptors, the acyl group is transferred to water. It is proposed that triacylglycerol synthesis proceeds via a sequential transfer of acyl groups from acyl-CoA ligase to the AAT, from which they are passed to the mono- and diacylglycerol acyltransferases for incorporation into the di- and triacylglycerols depending on the availability of the acyl acceptors. PMID- 7775413 TI - Implication of mammalian ribosomal protein S3 in the processing of DNA damage. AB - A human apurinic/apyrimidinic endonuclease activity, called AP endonuclease I, is missing from or altered specifically in cells cultured from Xeroderma pigmentosum group-D individuals (XP-D cells) (Kuhnlein, U., Lee, B., Penhoet, E. E., and Linn, S. (1978) Nucleic Acids Res. 5,951-960). We have now observed that another nuclease activity, UV endonuclease III, is similarly not detected in XP-D cells and is inseparable from the AP endonuclease I activity. This activity preferentially cleaves the phosphodiester backbone of heavily ultraviolet irradiated DNA at unknown lesions as well as at one of the phosphodiester bonds within a cyclobutane pyrimidine dimer. The nuclease activities have been purified from mouse cells to yield a peptide of M(r) = 32,000, whose sequence indicates identity with ribosomal protein S3. The nuclease activities all cross-react with immunopurified antibody directed against authentic rat ribosomal protein S3, and, upon expression in Escherichia coli of a cloned rat cDNA for ribosomal protein S3, each of the activities was recovered and was indistinguishable from those of the mammalian UV endonuclease III. Moreover, the protein expressed in E. coli and its activities cross-react with the rat protein antibody. Ribosomal protein S3 contains a potential nuclear localization signal, and the protein isolated as a nuclease also has a glycosylation pattern consistent with a nuclear localization as determined by lectin binding. The unexpected role of a ribosomal protein in DNA damage processing and the unexplained inability to detect the nuclease activities in extracts from XP-D cells are discussed. PMID- 7775415 TI - The Moloney leukemia retroviral long terminal repeat trans-activates AP-1 inducible genes and AP-1 transcription factor binding. AB - Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic retrovirus which causes T lymphomas. The long terminal repeat (LTR) of Mo-MuLV affects the regulation of a number of cellular genes, including collagenase IV, monocyte chemoattractant protein-1, and c-jun genes, all of which contain 12-O tetradecanoylphorbol-13-acetate-responsive element consensus sites within their promoters. We report here that Mo-MuLV stimulates the collagenase IV gene through transcription factor AP-1, and that the expression of a subgenomic portion of Mo MuLV LTR alone is sufficient for this effect. Transient or stable expression of the viral LTR increases cellular AP-1 DNA binding activity. The collagenase IV 12 O-tetradecanoylphorbol-13-acetate-responsive element consensus sequence was shown to be required for this trans-activation. Deletions or mutations of this consensus site which abolished AP-1 binding also abolished trans-activation by the LTR. Transient or stable transfection of the viral LTR into cells stimulated c-jun gene expression, suggesting one mechanism whereby the viral LTR may induce cellular AP-1 activity. Thus, the Mo-MuLV LTR, through activation of the transcription factor AP-1, is capable of regulating cellular gene expression, including the induction of proto-oncogenes. This activity may be relevant to the mechanisms whereby retroviruses which do not contain oncogenes induce neoplasia. PMID- 7775417 TI - Synthesis of a photoaffinity analog of 3'-azidothymidine, 5-azido-3'-azido-2',3' dideoxyuridine. Interactions with herpesvirus thymidine kinase and cellular enzymes. AB - Long term administration of 3'-azidothymidine (AZT) for the treatment of AIDS has led to detrimental clinical side effects in some patients, the biochemical causes of which are still being delineated. Base-substituted, azido-nucleotide photoaffinity analogs have routinely proven to be effective tools for identifying and characterizing nucleotide-utilizing enzymes. Therefore, we have synthesized 5 azido-3'-azido-2',3'-dideoxyuridine, which is a potential photoaffinity analog of two human immunodeficiency virus drugs, AZT and 3'azido-2',3'-dideoxyuridine. A partially purified herpes simplex virus type 1 thymidine kinase and [gamma 32P]ATP were used to make an AZT monophosphate analog, [32P]5-azido-3'-azido 2',3'-dideoxyuridine monophosphate. The photoaffinity properties of this analog were initially tested with herpes simplex virus type 1 thymidine kinase. Photoaffinity labeling of this enzyme was saturable (half-maximal, 30 microM) and could be specifically inhibited by AZT, AZT monophosphate, thymidine, and thymidine monophosphate. Photolabeling of rat liver microsomal membranes was also done, and several membrane proteins that interact with AZT monophosphate were identified. The antiviral and cytotoxic activities of 5-azido-3'-azido-2',3' dideoxyuridine were determined using human immunodeficiency virus, type 1 strain IIIB and an AZT drug-resistant strain in human T lymphocyte H9 cells. PMID- 7775416 TI - Thermal stability and domain-domain interactions in natural and recombinant protein C. AB - Scanning microcalorimetry and spectrofluorimetry were applied to a study of the thermal stability and interaction of the modules within natural human protein C (PC) and recombinant protein C (rPC), a potential therapeutic anticoagulant expressed in transgenic pigs. Upon heating in the presence of 2 mM EDTA, pH 8.5, each protein exhibited a similar heat absorption peak with a Tm of approximately 62 degrees C corresponding to the melting of the serine protease (SP) module. Deconvolution of this peak indicated that the SP module consists of two domains that unfold independently. At pH below 3.8, a second peak appeared at extremely high temperature corresponding to the unfolding of the two interacting epidermal growth factor-like (EGF) domains. This second peak occurred at a temperature about 20 degrees C lower in rPC than in PC indicating that the EGF domains in the recombinant protein are less stable. The isolated 6-kDa gamma-carboxyglutamic acid-rich (Gla) fragment as well as a 25-kDa Gla-(EGF)2 fragment both exhibited a sigmoidal fluorescence-detected denaturation transition in the same temperature region as the SP domains, but only in the presence of Ca2+. In 2 mM Ca2+, the first heat absorption peak in both intact proteins became biphasic, indicating Ca(2+)-induced structural changes. By contrast, Ca2+ had very little effect on the melting of Gla-domain-less protein C. This indicates that not Ca2+ itself but the Ca(2+)-loaded Gla domain is responsible for conformational changes in the SP domain of the parent protein. Detailed analysis of the shape of the endotherms obtained in Ca2+ and EDTA suggests that Ca2+ induces compact structure in the Gla domain which appears to interact strongly with the SP domain(s) of protein C. PMID- 7775419 TI - Promoter-dependent photocross-linking of the acidic transcriptional activator E2F 1 to the TATA-binding protein. AB - Sequence-specific transcriptional activators, such as the human factor E2F-1, increase the rate of initiation of transcription by RNA polymerase II, possibly by contacting one or more of the RNA polymerase II-associated general initiation factors. One candidate target of transactivators is the TATA-binding protein (TBP), which, when bound to a promoter, nucleates the formation of a preinitiation complex. Previous studies using affinity chromatography techniques have shown that the activation domains of certain activators, including the acidic activation domain of E2F-1, can interact with TBP in the absence of DNA. Using a site-directed photoaffinity cross-linking approach, we demonstrate here that the activation domain of the chimeric activator LexA-E2F-1 can be cross linked to TBP when both factors are bound to a transcriptionally responsive RNA polymerase II promoter. Mutations within the activation domain of LexA-E2F-1 that impaired its ability to activate transcription in vitro were found to reduce cross-linking of LexA-E2F-1 to TBP. The association of initiation factor TFIIB with the TBP-promoter complex did not preclude this promoter-dependent cross linking to LexA-E2F-1; however, this cross-linking was promoter-independent. In contrast, TFIIA strongly inhibited the promoter-dependent cross-linking of LexA E2F-1 to TBP. These results directly demonstrate that acidic activators such as E2F-1 can interact with TBP during the earliest stages in the assembly of an RNA polymerase II preinitiation complex. PMID- 7775420 TI - Metabolic sources of hydrogen peroxide in aerobically growing Escherichia coli. AB - Exposure of cells to hydrogen peroxide (H2O2) mediates adaptive responses or oxidative damage, depending on the magnitude of the challenge. Determining the threshold for peroxide-mediated oxidative stress thus requires quantitation of the changes in endogenous H2O2 production. The intracellular steady-state concentrations of H2O2 were measured in intact Escherichia coli under different conditions. Compounds that block electron transport at NADH dehydrogenase (rotenone) or between ubiquinone and cytochrome b (antimycin) showed that univalent reduction of O2 can occur at these sites in vivo to form superoxide anion (O2-), in agreement with reports for mammalian mitochondria. Mutational inactivation of different components of the respiratory chain showed that H2O2 production also depended on the energy status of the cell and on the arrangement of respiratory chain components corresponding to particular growth conditions. Production rates for O2- and H2O2 were linearly related to the number of active respiratory chains that reached maximal values during exponential growth. In the strains defective in respiratory chain components, catalase activity was regulated to compensate for changes in the H2O2 production rates, which maintained intracellular H2O2 at 0.1-0.2 microM during aerobic growth over a wide range of cell densities. The expression of a katG'::lacZ fusion (reporting transcriptional control of the catalase-hydroperoxidase I gene) was increased by H2O2 given either as a pulse or as a steady production. This response not only depended on the type and severity of the stimulus but was also strongly influenced by the growth phase of the cells. PMID- 7775421 TI - Expression of the leukocyte-associated sialoglycoprotein CD43 by a colon carcinoma cell line. AB - The colon adenocarcinoma cell line COLO 205 secretes L-CanAg, a mucin-like glycoprotein carrying the carcinoma-associated sialyl-Lewis a carbohydrate epitope. In an attempt to identify its apoprotein, an NH2-terminal peptide sequence was obtained from purified L-CanAg. In all interpretable positions, this sequence showed 100% identity to the NH2-terminal of human CD43 (leukosialin, sialophorin), a plasma membrane-bound sialoglycoprotein hitherto only identified in leukocytes and other hematopoietic cells. An antiserum against deglycosylated L-CanAg and an anti-CD43 antiserum both immunoprecipitated a 61-kDa band, interpreted as the CD43 precursor, from COLO 205 cells as well as from the known CD43-expressing cell line HL-60. Results from immunoprecipitations following pulse-chase experiments and tunicamycin treatments were in agreement with earlier studies on the CD43 precursor. RNA blot analysis confirmed the expression of CD43 by the COLO 205 cell line, whereas three other colon carcinoma cell lines were negative. The glycosylation-dependent monoclonal antibody Leu-22, which recognizes leukocyte CD43, failed to bind L-CanAg, probably due to its much more extensive glycosylation. We conclude that L-CanAg is the secreted extracellular domain of a novel glycoform of CD43 and that CD43, if expressed in other carcinoma cells, may have escaped notice in studies relying on glycosylation dependent monoclonal antibodies against leukocyte CD43. PMID- 7775418 TI - Characterization of a mucin cDNA clone isolated from HT-29 mucus-secreting cells. The 3' end of MUC5AC? AB - HT-29 cells resistant to 10(-6) M methotrexate (HT29-MTX) secrete mucins with gastric immunoreactivity (Lesuffleur, T., Barbat, A., Dussaulx, E., and Zweibaum, A. (1990) Cancer Res. 50, 6334-6343). A 3310-base pair mucin cDNA clone (L31) was isolated from an HT29-MTX expression library using a polyclonal serum specific for normal gastric mucosa. It shows a high level of identity (98.6%) to clone NP3a isolated from a nasal polyp cDNA library (Meerzaman, D., Charles, P., Daskal, E., Polymeropoulos, M. H., Martin, B. M., and Rose, M. C. (1994) J. Biol. Chem. 269, 12932-12939). However, as a result of changes in reading frame, the 1042-amino acid deduced peptide contains four regions of a low similarity to the NP3a peptide. The amino acid sequence shows 36.3% similarity to part of the carboxyl-terminal sequence of MUC2 including the so-called D4 domain and 21.3% to the pro von Willebrand factor. A short amino acid sequence is similar to cysteine rich sequences repeated in tracheobronchial, gastric, and colonic mucin cDNAs. The gene corresponding to L31 is located in the mucin gene cluster on chromosome 11p15.5. The patterns of mRNA expression were indistinguishable from those revealed with the JER58 probe (MUC5AC). Southern blot analysis indicates that the L31 and JER 58 sequences are within 20 kilobase pairs of each other. Together, these results suggest that L31 clone is the 3' end of MUC5AC. PMID- 7775422 TI - Cytosolic ADP-ribosylation factors are not required for endosome-endosome fusion but are necessary for GTP gamma S inhibition of fusion. AB - A specific role for ADP-ribosylation factors (ARFs) in in vitro endosome-endosome fusion has been proposed (Lenhard, J. M., Kahn, R. A., and Stahl, P. D. (1992) J. Biol. Chem. 267, 13047-13052). However, in vivo studies have failed to support a function for ARFs in the endocytic pathway, since an antagonist of ARF activities, brefeldin A, does not interfere with receptor internalization (Schonhorn, J. E., and Wessling-Resnick, M. (1994) Mol. Cell. Biochem. 135, 159 164). This controversy surrounding the exact function of ARF in endocytic vesicle traffic prompted us to critically re-examine the involvement of ARFs in cell-free endosome fusion. Cytosol depleted of ARF activity was capable of supporting in vitro endocytic vesicle fusion but failed to support inhibition of this reaction in the presence of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). Addition of purified ARF1 restored the ability of the ARF-depleted cytosol to inhibit endosome fusion when incubated with GTP gamma S. Both endocytic vesicle fusion and the GTP gamma S-mediated inhibition of vesicle fusion were unaffected by brefeldin A. Moreover, the ATP requirement and kinetics of cell-free fusion are not altered by brefeldin A or depletion of cytosolic ARFs. These results suggest that cytosolic ARFs are not necessary for endosomal vesicle fusion in vitro but are responsible for inhibition of fusion in the presence of GTP gamma S and cytosolic factors in a brefeldin A-resistant manner. PMID- 7775423 TI - Overproduction and one-step purification of Escherichia coli 3-deoxy-D-manno octulosonic acid 8-phosphate synthase and oxygen transfer studies during catalysis using isotopic-shifted heteronuclear NMR. AB - The enzyme 3-deoxy-D-manno-octulosonic acid 8-phosphate synthase catalyzes the condensation of D-arabinose 5-phosphate with phosphoenolpyruvate to give the unique 8-carbon acidic sugar 3-deoxy-D-manno-octulosonic acid 8-phosphate (KDO 8 P) found only in Gram-negative bacteria and required for lipid A maturation and cellular growth. The Escherichia coli gene kdsA that encodes KDO 8-P synthase has been amplified by polymerase chain reaction methodologies and subcloned into the expression vector, pT7-7. A simple one-step purification yields 200 mg of homogeneous KDO 8-P synthase per liter of cell culture. [2 13C,18O]Phosphoenolpyruvate (PEP) was prepared by first, exchange of [2-13C]-3 bromopyruvate with 2H2 18O followed by reaction of the labeled bromopyruvate with trimethylphosphite. The fate of the enolic oxygen in this multilabeled PEP, during the course of the KDO 8-P synthase-catalyzed reaction with D-arabinose 5 phosphate, was monitored by 13C and 31P NMR spectroscopy. The inorganic phosphate formed during the reaction was further analyzed via mass spectral analysis of its trimethyl ester derivative. The 13C NMR spectrum of an incubation mixture of [2 13C]PEP and D-arabinose 5-phosphate in 2H2 18O in the presence of KDO 8-P synthase was also recorded. [2-13C]KDO 8-P was utilized to determine the extent of nonenzymatic incorporation of 18O into the C-2 position of KDO 8-P. The results indicate that the enolic oxygen of the PEP is recovered with the inorganic phosphate, and the C-2 oxygen of KDO 8-P originates from the solvent, H2O. PMID- 7775424 TI - Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. AB - Mice that are homozygous for the targeted disruption of the gene encoding the B2 bradykinin receptor have been generated. The gene disruption results in a deletion of the entire coding sequence for the B2 receptor. The disruption of the B2 receptor gene has been confirmed by genetic, biochemical, and pharmacological analyses. Mice that are homozygous for the disruption of the B2 receptor gene are fertile and indistinguishable from their littermates by visual inspection. Bradykinin fails to produce responses in pharmacological preparations from ileum, uterus, and the superior cervical ganglia from these mice. Therefore, expression of a single gene appears to be responsible for conferring responsiveness to bradykinin in these tissues. PMID- 7775425 TI - Identification of a sixth promoter that directs the transcription of gamma glutamyl transpeptidase type III RNA in mouse. AB - We have previously identified five promoters in the 5'-flanking region of the mouse gamma-glutamyl transpeptidase (gamma GT) gene. We now report the localization of a sixth promoter that supports the transcription of type III RNA, the major gamma GT RNA in fetal liver. We made a fetal liver cDNA library enriched for gamma GT RNA and obtained 12 gamma GT type III-specific clones. The longest clone is consistent with a transcription start site for type III RNA at a position 5' to the type IV promoter and about 5 kilobase(s) (kb) 5' to the first coding exon. We estimated by ribonuclease protection assay that about 80% of the gamma GT mRNA in fetal liver was type III. Primer extension and nuclease protection analyses mapped the 5' end of type III mRNA in fetal liver and kidney to a single cluster of potential major and minor transcription start sites. Deletion analysis using transient expression of chloramphenicol acetyltransferase constructs of the type III promoter region revealed the greatest activity with a 1-kb 5'-flanking fragment in mouse kidney proximal tubular cells and no detectable activity in NIH-3T3 fibroblasts. These studies demonstrate that the type III 5' region of the mouse gamma GT gene is organized into two distinct exons (IIIa and IIIb) and that type III RNA is expressed under the control of its own promoter. PMID- 7775426 TI - Separate C-terminal domains of the epithelial specific brush border Na+/H+ exchanger isoform NHE3 are involved in stimulation and inhibition by protein kinases/growth factors. AB - NHE3, a cloned intestinal and renal brush border Na+/H+ exchanger, has previously been shown to be both stimulated and inhibited by different protein kinases/growth factors. For instance, NHE3 is stimulated by serum and fibroblast growth factor (FGF) and inhibited by protein kinase C. In the present study, we used a series of NHE3 C terminus truncation mutants to identify separate regions of the C-terminal cytoplasmic tail responsible for stimulation and inhibition by protein kinases/growth factors. Five NHE3 C terminus truncation mutant stable cell lines were generated by stably transfecting NHE3 deletion cDNAs into PS120 fibroblasts, which lack any endogenous Na+/H+ exchanger. Using fluorometric techniques, the effects of the calcium/calmodulin (CaM) inhibitor W13, calcium/CaM kinase inhibitor KN-62, phorbol myristate acetate, okadaic acid, FGF, and fetal bovine serum on Na+/H+ exchange were studied in these transfected cells. Inhibition of basal activity of full-length NHE3 is mediated by CaM at a site C-terminal to amino acid 756; this CaM effect occurs through both kinase dependent and independent mechanisms. There is another independent inhibitory domain for protein kinase C between amino acids 585 and 689. In addition, there are at least three stimulatory regions in the C-terminal domain of NHE3, corresponding to amino acids 509-543 for okadaic acid, 475-509 for FGF, and a region N-terminal to amino acid 475 for fetal bovine serum. We conclude that separate regions of the C terminus of NHE3 are involved with stimulation or inhibition of Na+/H+ exchange activity, with both stimulatory and inhibitory domains having several discrete subdomains. A conservative model to explain the way these multiple domains in the C terminus of NHE3 regulate Na+/H+ exchange is via an effect on associated regulatory proteins. PMID- 7775428 TI - Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms. AB - We obtained three types of cDNA clones homologous to Ash/Grb2(Ash-l) cDNA from rats. One of these clones, Ash-psi, was an unusual transcribed gene having 93% identity in the nucleotide sequence to Ash-l. The other two clones, Ash-m and -s, had nucleotide sequences identical with Ash-l cDNA in the amino-terminal region. The coding sequence of Ash-m cDNA is 42 nucleotides shorter than that of Ash-l cDNA. The defective region of Ash-m cDNA encodes 14 amino acid residues (157 to 170 of Ash-l), which comprise the most conserved region of the second SH3 domain. On the other hand, the coding sequence of Ash-s terminated at the end of the first SH3 domain due to a stop codon at the boundary of the sequence, thereby differing from Ash-l cDNA. Cloning of the genomic DNA of the Ash-l-encoding gene, determination of the gene organization, and nucleotide sequencing revealed that the two isoforms, as well as Ash-l, are generated from a single gene by unusual alternative splicings. The gene spans more than 16 kilobases and contains 6 exons and 5 introns. Ash-m and Ash-s mRNAs were detected in various tissues by reverse transcribed polymerase chain reaction. Ash-m physically associated with dynamin, but the association with Sos was less effective than that of Ash-l in rat pheochromocytoma PC12 cell lysates, irrespective of treatment with nerve growth factor. In contrast, Ash-s formed a complex with dynamin and Sos in cell lysates. Moreover, the newly formed carboxyl-terminal SH3 of Ash-m by splicing bound different proteins from those bound to the carboxyl-terminal SH3 domain of Ash-l, suggesting that Ash-m generates different signals. Microinjection of Ash-m or Ash s into Balb/c 3T3 cells inhibited DNA synthesis induced by platelet-derived growth factor. These results show that these isoforms act as dominant negative regulators of mitogenic signals by Ash-l. PMID- 7775427 TI - The Saccharomyces cerevisiae VMA10 is an intron-containing gene encoding a novel 13-kDa subunit of vacuolar H(+)-ATPase. AB - The vacuolar H(+)-ATPase (V-ATPase) functions as a primary proton pump that generates an electrochemical gradient of protons across the membranes of several internal organelles. It is composed of distinct catalytic and membrane sectors, each containing several subunits. We identified a protein (M16) that copurifies with the V-ATPase complex from Saccharomyces cerevisiae and appears to be present at multiple copies/enzyme. Amino acid sequencing of its proteolytic products yielded three nonoverlapping peptide sequences matching an unidentified reading frame located on chromosome VIII. Sequence analysis of cDNA encoding M16 revealed that the gene encoding this protein (VMA10) is interrupted by a 162-nucleotide intron that begins after the ATG codon of the initiator methionine. The cDNA encodes an hydrophilic protein of 12,713 Da with a basic isoelectric point of pH 9. A delta vma10::URA3 null mutant exhibited growth characteristics typical of other vma disruptant mutants in genes encoding subunits of V-ATPase. The null mutant does not grow on medium buffered at pH 7.5. It fails to accumulate quinacrine into its vacuole, and subunits of the catalytic sector are not assembled onto the vacuolar membrane in the absence of M16. A cold inactivation experiment demonstrated that M16 is a subunit of the membrane sector of V-ATPase. M16 exhibits a significant sequence homology with subunit b of F-ATPase membrane sector. PMID- 7775429 TI - Spectral characterization and chemical modification of catalase-peroxidase from Streptomyces sp. AB - Catalase-peroxidase was purified to near homogeneity from Streptomyces sp. The enzyme was composed of two subunits with a molecular mass of 78 kDa and contained 1.05 mol of protoporphyrin IX/mol of dimeric protein. The absorption and resonance Raman spectra of the native and its cyano-enzyme were closely similar to those of other heme proteins with a histidine as the fifth ligand. However, the peak from tyrosine ring at approximately 1612 cm-1, which is unique in catalases, was not found in resonance Raman spectra of catalase-peroxidase. The electron paramagnetic resonance spectrum of the native enzyme revealed uniquely two sets of rhombic signals, which were converted to a single high spin, hexacoordinate species after the addition of sodium formate. Cyanide bound to the sixth coordination position of the heme iron, thereby converting the enzyme to a low spin, hexacoordinate species. The time-dependent inactivation of the enzyme with diethyl pyrocarbonate and its kinetic analysis strongly suggested the occurrence of histidine residue. From the above-mentioned spectroscopic results and chemical modification, it was deduced that the native enzyme is predominantly in the high spin, ferric form and has a histidine as the fifth ligand. PMID- 7775430 TI - Chimeric muscle and brain glycogen phosphorylases define protein domains governing isozyme-specific responses to allosteric activation. AB - Muscle and brain glycogen phosphorylases differ in their responses to activation by phosphorylation and AMP. The muscle isozyme is potently activated by either phosphorylation or AMP. In contrast, the brain isozyme is poorly activated by phosphorylation and its phosphorylated a form is more sensitive to AMP activation when enzyme activity is measured in substrate concentrations and temperatures encountered in the brain. The nonphosphorylated b form of the brain isozyme also differs from the muscle isozyme b form in its stronger affinity and lack of cooperativity for AMP. To identify the structural determinants involved, six enzyme forms, including four chimeric enzymes containing exchanges in amino acid residues 1-88, 89-499, and 500-842 (C terminus), were constructed from rabbit muscle and human brain phosphorylase cDNAs, expressed in Escherichia coli, and purified. Kinetic analysis of the b forms indicated that the brain isozyme amino acid 1-88 and 89-499 regions each contribute in an additive fashion to the formation of an AMP site with higher intrinsic affinity but weakened cooperativity, while the same regions of the muscle isozyme each contribute to greater allosteric coupling but weaker AMP affinity. Kinetic analysis of the a forms indicated that the amino acid 89-499 region correlated with the reduced response of the brain isozyme to activation by phosphorylation and the resultant increased sensitivity of the a form to activation by saturating levels of AMP. This isozyme-specific response also correlated with the glycogen affinity of the a forms. Enzymes containing the brain isozyme amino acid 89-499 region exhibited markedly reduced glycogen affinities in the absence of AMP compared to enzymes containing the corresponding muscle isozyme region. Additionally, AMP led to greater increases in glycogen affinity of the former set of enzymes. In contrast, phosphate affinities of all a forms were similar in the absence of AMP and increased approximately the same extent in AMP. The potential importance of a number of isozyme-specific substitutions in these sequence regions is discussed. PMID- 7775432 TI - Structural requirement for cell adhesion to kalinin (laminin-5). AB - Laminin-5 (kalinin) was purified from spent cell culture media (SCC25 cells) by affinity chromatography on monoclonal antibody BM165. The protein was recovered as a mixture of the typical polypeptides of 165-155, 140, and 105 kDa as judged b SDS-polyacrylamide gel electrophoresis analysis under reducing conditions. The amino acid composition of purified laminin-5 was in agreement with that compiled from the recently published cDNA sequences of the alpha 3-, beta 3-, and gamma 2 laminin chains. Moreover, the content of half-cystine residues in laminin-5 was about two-thirds that in laminin-1, which confirms the prediction of a smaller number of epidermal growth factor-like repeats in the amino-terminal portion of the three chains. The content of coiled-coil alpha-helices (27%) determined by CD spectroscopy was comparable to that reported for laminin-1, which indicates that the long arm portion of laminin-5 is equivalent to that of other laminin isoforms. The melting temperature was recorded at 72 degrees C by CD monitoring of unfolding and refolding of the coiled-coil structures during thermal denaturation and renaturation, respectively. The thermal stability of laminin-5 is therefore significantly higher than that of laminin-1 or alpha 2-chain containing laminins, which suggests higher ionic interactions between the three polypeptide chains of laminin-5. Cell adhesion-promoting activity of laminin-5 was found to be strictly and entirely dependent on the presence of coiled-coil structures. It decreased gradually after heat denaturation of the protein above 65 degrees C and was totally abrogated at 75 degrees C. This is in contrast to laminin-1, which contains both conformation-dependent and -independent cell binding sites on the long and short arm domains, respectively. PMID- 7775431 TI - Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. AB - A monoclonal antibody (mAb) was isolated that blocked the binding and bioactivity of both human and murine interleukin 1 beta (IL-1 beta) on murine IL-1 receptor bearing cells. This mAb recognized a protein that was distinct from the Type I and Type II IL-1 receptors, suggesting that an additional protein exists that is involved in IL-1 biological responses. By expression cloning in COS-7 cells, we have isolated a cDNA from mouse 3T3-LI cells encoding this putative auxiliary molecule, which we term the IL-1 receptor accessory protein (IL-1R AcP). Sequence analysis of the cDNA predicts an open reading frame that encodes a 570-amino acid protein with a molecular mass of approximately 66 kDa. The IL-1R AcP is a member of the Ig superfamily by analysis of its putative extracellular domain and also bears limited homology throughout the protein to both Type I and Type II IL-1 receptors. Northern analysis reveals that murine IL-1R AcP mRNA is expressed in many tissues and appears to be regulated by IL-1. In mammalian cells expressing natural or recombinant Type I IL-1R and IL-1R AcP, the accessory protein forms a complex with the Type I IL-1R and either IL-1 alpha or IL-1 beta but not IL-1ra. The recombinant accessory protein also increases the binding affinity of the recombinant Type I IL-1R for IL-1 beta when the two receptor proteins are coexpressed. Therefore, the functional IL-1 receptor appears to be a complex composed of at least two subunits. PMID- 7775433 TI - Double bond removal from odd-numbered carbons during peroxisomal beta-oxidation of arachidonic acid requires both 2,4-dienoyl-CoA reductase and delta 3,5,delta 2,4-dienoyl-CoA isomerase. AB - The pathway for the peroxisomal beta-oxidation of arachidonic acid (5,8,11,14 20:4) was elucidated by comparing its metabolism with 4,7,10-hexadecatrienoic acid (4,7,10-16:3) and 5,8-tetradecadienoic acid (5,8-14:2) which are formed, respectively, after two and three cycles of arachidonic acid degradation. When [1 14C]4,7,10-16:3 was incubated with peroxisomes in the presence of NAD+ and NADPH, it resulted in a time-dependent increase in the production of acid-soluble radioactivity which was accompanied by the synthesis of 2-trans-4,7,10 hexadecatetraenoic acid and two 3,5,7,10-hexadecatetraenoic acid isomers. The formation of conjugated trienoic acids suggests that peroxisomes contain delta 3,5,delta 2,4-dienoyl-CoA isomerase with the ability to convert 2-trans-4,7,10 hexadecatetraenoic acid to 3,5,7,10-hexadecatetraenoic acid. When 1-14C-labeled 6,9,12-octadecatrienoic acid or 7,10,13,16-docosatetraenoic acid was incubated without nucleotides, the 3-hydroxy metabolites accumulated, since further degradation requires NAD(+)-dependent 3-hydroxyacyl-CoA dehydrogenase. When [1 14C]5,8,11,14-20:4 was incubated under identical conditions, no polar metabolite was detected, but 2-trans-4,8,11,14-eicosapentaenoic acid accumulated. When NADPH was added to incubations, 3-hydroxy-8,11,14-eicosatrienoic, 2-trans-4,8,11,14 eicosapentaenoic, 2-trans-8,11,14-eicosatetraenoic, and 8,11,14-eicosatrienoic acids were produced. Analogous compounds were formed from [1-14C]5,8-14:2. Our results show that the removal of double bonds from odd-numbered carbons in arachidonic acid thus requires both NADPH-dependent 2,4-dienoyl-CoA reductase and delta 3,5,delta 2,4-dienoyl-CoA isomerase. One complete cycle of 5,8-14:2 and 5,8,11,14-20:4 beta-oxidation yields, respectively, 6-dodecenoic and 6,9,12 octadecatrienoic acids. PMID- 7775434 TI - Coupled reactions in hemoglobin. Heme-globin and dimer-dimer association. AB - Five different human hemoglobins were used to test the postulate that dissociation of hemoglobin (Hb) tetramers into alpha beta dimers and dissociation of heme from globin are linked reactions. Spectrophotometric measurements of the initial rate of heme transfer from Hb to serum albumin were made over a 3000-fold range of Hb concentration and yielded the heme-globin dissociation rate constant for tetramers and that for dimers. The tetramer-dimer dissociation constant (K4,2) could then be calculated from the rate constant at intermediate concentrations. The values obtained for the five hemoglobins, spanning a 250-fold range in K4,2, were in good agreement with those found by direct methods. The relation between this new linkage reaction of hemoglobin and the classical ones, such as the reciprocal relation between the binding of oxygen and protons, is discussed briefly. PMID- 7775435 TI - The nuclear pore complex protein p62 is one of several sialic acid-containing proteins of the nuclear envelope. AB - While investigating the glycosylation of nuclear envelope proteins of neuroblastoma cells, we found several proteins that bound the sialic acid specific Sambucus nigra agglutinin. The strongest signals were obtained for proteins with apparent molecular masses of 66 and 180 kDa. The specificity of the lectin binding was checked by acylneuraminyl hydrolase treatment of nuclear envelope proteins, which prohibited S. nigra agglutinin binding. Digestion of nuclear envelope proteins with the N-glycosidase F revealed that sialic acid was N-glycosidically linked to the 180-kDa protein and very probably O-glycosidically linked to the 66-kDa protein. Upon extraction, the latter behaved like the nucleoporin p62 in that it was partly extracted by high ionic strength buffers, could not be solubilized by nonionic detergent, and was completely removed from the nuclear envelope with urea. Two-dimensional gel electrophoretic comparison showed that the S. nigra agglutinin-binding protein and p62 have an identical isoelectric point of about 5.0 and an identical apparent molecular mass of 66 kDa. This, together with the binding of the anti-nucleoporin antibody, demonstrated the identity of the 66-kDa sialoprotein and p62. S. nigra agglutinin inhibits nuclear protein transport in neuroblastoma cells, strongly suggesting a functional significance of sialylation of p62. PMID- 7775436 TI - Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiator. AB - Contrary to its effects on the gamma-aminobutyric acid type A receptor, picrotoxin antagonism of the alpha 1 subunit of the human glycine receptor is shown to be competitive, not use-dependent, and nonselective between the picrotoxin components, picrotin, and picrotoxinin. Competitive antagonism and non use dependence are consistent with picrotoxin binding to a site in the extracellular domain. The mutations Arg-->Leu or Arg-->Gln at residue 271 of the glycine receptor alpha 1 subunit, which are both associated with human startle disease, have previously been demonstrated to disrupt the transduction process between agonist binding and channel activation. We show here that these mutations also transform picrotoxin from an allosterically acting competitive antagonist to an allosteric potentiator at low (0.01-3 microM) concentrations and to a noncompetitive antagonist at higher (> or = 3 microM) concentrations. This demonstrates that arginine 271 is involved in the transduction process between picrotoxin binding and its mechanism of action. Thus, the allosteric transduction pathways of both agonists and antagonists converge at a common residue prior to the activation gate of the channel, suggesting that this residue may act as an integration point for information from various extracellular ligand binding sites. PMID- 7775437 TI - Purification of a variant-specific surface protein of Giardia lamblia and characterization of its metal-binding properties. AB - Giardia lamblia, an intestinal parasite of humans and other vertebrates, undergoes surface antigenic variation by modulating the expression of different variant-specific surface proteins (VSP). VSPs are cysteine-rich surface proteins that bind zinc and other heavy metals in vitro. We developed an immunoaffinity chromatographic method to purify a VSP in order to determine its biochemical properties. The sequences of two different proteolytic fragments agreed with the sequence deduced from the cloned gene, and amino-terminal sequence indicated the removal of a 14-residue signal peptide, consistent with the transport of VSP to the cell surface. The protein is not glycosylated and has an isoelectric point of 5.3. X-ray microanalyses indicated that the major metals in Giardia trophozoites, as well as purified VSP, are zinc and iron. The zinc concentration in Giardia cells was found to be 0.43 mM and the iron concentration 0.80 mM when compared with standard samples (zinc) or calculated from a known physical constants (iron). We propose that metal coordination stabilizes VSPs, rendering them resistant to proteolytic attack in the upper small intestine. Moreover, the ability to bind ions by Giardia may play a role in nutritional deficiency and/or malabsorption in heavily infected persons. PMID- 7775438 TI - The amino-terminal portion of the JAK2 protein kinase is necessary for binding and phosphorylation of the granulocyte-macrophage colony-stimulating factor receptor beta c chain. AB - The binding of granulocyte-macrophage colony stimulating factor (GM-CSF) to its receptor stimulates JAK2 protein kinase activation, protein phosphorylation, and JAK2 association with the beta c chain of the GM-CSF receptor. To better understand how different domains of the JAK2 function to regulate association and phosphorylation of the beta c receptor, the minimal portion of the beta c receptor necessary for JAK2 binding has been determined. Using glutathione S transferase (GST) fusion proteins expressing different portions of the membrane proximal domain of the beta c chain, we demonstrate that JAK2 binds to amino acids 458-495, but showed little binding to fusion proteins containing amino acids 483-559, 483-530, or 458-484. The GST-beta c 458-495 bound equally well to the wild type (WT) JAK2, a carboxyl-terminal deletion of JAK2 removing the protein kinase domain (amino acids 1000-1129), and a deletion of the kinase-like domain (amino acids 523-746). However, an amino-terminal JAK2 deletion (amino acids 2-239) markedly reduced binding to this GST-beta c. Far Western blotting demonstrated that a GST fusion protein containing amino acids 1-294 of JAK2, but not fusion proteins containing amino acids 295-522, 523-746, or 747-1127, bound GST-beta c 458-559. When the JAK2 WT and deletions were transiently expressed along with the alpha and beta c subunits of the GM-CSF receptor and the cells were treated with GM-CSF, the following results were obtained: 1) WT JAK2 phosphorylated the beta c subunit in a GM-CSF-dependent manner, 2) the kinase like domain deletion phosphorylated the beta c subunit, and 3) both the kinase domain deletion and the amino-terminal deletion failed to stimulate phosphorylation of the beta c subunit. Therefore, phosphorylation of the beta c subunit requires the binding of JAK2 through its amino terminus. PMID- 7775439 TI - Pentobarbital-induced changes in Drosophila glutathione S-transferase D21 mRNA stability. AB - The Drosophila glutathione S-transferase (gstD) genes are a family of divergently transcribed, intronless genes and pseudogenes. Under control conditions, the steady-state level of gstD1 mRNA is 20-fold higher than that of the gstD21 mRNA despite a lower transcription rate of the gstD1 gene. The GST D1 protein level is four times as abundant as the GST D21 protein. The gstD1 and gstD21 genes responded rapidly to pentobarbital (PB) as changes in mRNA levels were detectable within 30 min of treatment. Maximal induction of gstD1 and gstD21 resulted in 3 fold and 20-fold elevation of their respective mRNA levels. The major mechanism for the increase in gstD1 mRNAs appears to be transcriptional activation. The 2 fold increase in the rate of gstD21 transcription, however, cannot fully account for the 20-fold increase in the steady-state level of gstD21 mRNA. Therefore, post-transcriptional mechanism(s) should also be responsible for the increase of gstD21 mRNA by PB. Because the gstD21 mRNA is relatively unstable under control conditions, induction of the intronless gstD21 mRNA by PB occurs mainly at the level of enhanced mRNA stability. The GST D1 protein level in adult Drosophila was increased approximately 2-fold after PB treatment, whereas the GST D21 level remained relatively the same. Thus, an increase in gstD21 mRNA stability by PB treatment is probably coupled to a regulatory effect at the translational level. PMID- 7775440 TI - A mechanism for inhibition of factor VIII binding to phospholipid by von Willebrand factor. AB - von Willebrand factor (vWf) acts as a carrier for blood coagulation factor VIII (fVIII) in the circulation. The amino-terminal 272 residues of mature vWf contain a high affinity fVIII binding site. Upon thrombin activation, fVIII is released from vWf, thereby allowing its binding to phospholipid which is required for its procoagulant activity. Although phospholipid and vWf compete for fVIII binding, it was previously suggested that their binding sites are not closely juxtaposed within the fVIII protein because only amino-terminal vWf proteolytic fragments larger than SPIII-T4 (1-272) were able to block the binding of fVIII to phospholipid. We have demonstrated, however, that SPIII-T4 is able to inhibit fVIII binding to phosphatidylserine (PS) in a dose-dependent fashion, but only at concentrations higher than those used in previous experiments. Our demonstration that the Kd values for vWf and SPIII-T4 for fVIII are 0.52 nM and 48 nM, respectively, explain this discrepancy. Inhibition (> 95%) of SPIII-T4 binding to fVIII by a purified recombinant fVIII C2 domain polypeptide demonstrated that SPIII-T4 binds directly to C2, as we had previously shown for vWf. The similarity of the C2 binding sites for vWf and SPIII-T4 was further confirmed by the identical inhibitory effects of synthetic peptides and monoclonal antibodies (mAbs) on vWf-fVIII or SPIII-T4 fVIII binding. In both cases, binding was inhibited by synthetic peptide 2303-2332, containing a PS binding site, and by mAb NMC-VIII/5 Fab' (epitope within C2 residues 2170-2327). We propose that vWf, via residues 1-272, and PS compete for fVIII binding because they recognize overlapping sites within fVIII C2 domain residues 2303-2332. PMID- 7775441 TI - Sphingolipid biosynthesis de novo by rat hepatocytes in culture. Ceramide and sphingomyelin are associated with, but not required for, very low density lipoprotein secretion. AB - Sphingolipids are constituents of liver and lipoproteins, but relatively little is known about their synthesis and secretion. Incubation of rat hepatocytes with [14C]- or [3H]serine labeled the long-chain base backbones of mainly ceramide and sphingomyelin. Most of the labeled sphingolipids were associated with the cells; however, 1-5% (the majority of which was ceramide) was released into the medium as part of very low density lipoproteins (VLDL). Since this is the first report that lipoproteins contain ceramide, lipoproteins were isolated from rat plasma, and the ceramide contents were (per mg of protein): 6.5 nmol for VLDL (d < 1.018), 0.6 nmol for low density lipoproteins (1.018 < d < 1.063), 0.2 nmol for high density lipoproteins (1.063 < d < 1.18), and 0.1 nmol for the albumin fraction; the lipoproteins also contained 0.1-0.4 nmol of free sphingosine/mg of protein. A number of factors affected the secretion of radiolabeled sphingolipids: 1) addition of palmitic acid, but not stearic or oleic acid, enhanced secretion due to an increase in long-chain base synthesis de novo. 2) Choline deficiency caused a 42% reduction in the secretion of radiolabeled sphingomyelin, but this was due to an effect on VLDL secretion rather than a decrease in sphingolipid synthesis. Removal of choline was examined because previous studies (Yao, Z. M., and Vance, D. E. (1988) J. Biol. Chem. 263, 2998 3004) have shown that choline deficiencies depress phosphatidylcholine synthesis and lipoprotein secretion. 3) Incubation of the cells with fumonisin B1, a mycotoxin inhibitor of sphinganine (sphingosine) N-acyltransferase, reduced overall sphingolipid synthesis and secretion by 90%, but had no effect on the secretion of apoB, phosphatidylcholine, or cholesterol. All together, these findings demonstrate that rat hepatocytes synthesize ceramide and sphingomyelin de novo and incorporate them into both cellular membranes and secreted VLDL, but normal sphingolipid synthesis is not required for lipoprotein secretion. PMID- 7775442 TI - Dimerization of the TATA binding protein. AB - The TATA binding protein (TBP) is a central component of all eukaryotic transcription machineries. The recruitment of TBP to the promoter is slow and possibly rate limiting in transcription complex assembly. In an effort to understand the nature of this potential rate-limiting step, we have investigated the physical state of TBP prior to DNA binding. By chemical cross-linking, gel filtration chromatography, and protein affinity chromatography, we find that the conserved carboxyl-terminal DNA binding domain of human TBP dimerizes when not bound to DNA. The data completely support the proposed dimeric structure of plant TBP, previously determined by x-ray crystallography. TBP dimers are quite stable, having an approximate equilibrium dissociation constant (KD) in the low nanomolar range. The dimerization interface appears to be dominated by hydrophobic forces, as predicted by the crystal structure. TBP dimers do not bind DNA, but they must dissociate into monomers before stably binding to the TATA box. Dissociation of TBP dimers appears to be relatively slow, and as such has the potential to dictate the kinetics of DNA binding. PMID- 7775443 TI - Evidence for functional binding and stable sliding of the TATA binding protein on nonspecific DNA. AB - The TATA binding protein (TBP) is required at RNA polymerase I, II, and III promoters that either contain or lack a TATA box. In an effort to understand how TBP might function at such a wide variety of promoters, we have investigated the specific and nonspecific DNA binding properties of human TBP. We show that TBP has less than a 10(3)-fold preference for binding a TATA box (TATAAAAG) than for an average nonspecific site. In contrast to TBP, which binds to the minor groove of DNA, major groove binding proteins typically display binding specificities in the range of 10(6). Once TBP is bound to DNA, whether it be a TATA box or nonspecific DNA, binding is quite stable with a t1/2 of dissociation in the range of 20-60 min for a 300-base pair DNA fragment. In this binding state, TBP appears to be capable of stable one-dimensional sliding along the DNA. Sequence-specific binding can be accounted for, in part, by different rates of sliding. Additional findings demonstrate that specific and nonspecific DNA impart upon TBP an enormous and equivalent degree of thermal stability, suggesting that the TBP-DNA interface on non-specific DNA is not radically different from that on TATA. Consistent with this notion, we find that nonspecifically bound TBP is competent in establishing pol II transcription complexes on DNA. Together, these finding provide a plausible mechanistic explanation for the ability of TBP to function at TATA-containing and TATA-less promoters. PMID- 7775444 TI - The role of water in retinal complexation to bacterio-opsin. AB - A system is described that allows for the delineation of the factors that effect the complexation of retinal to the apoprotein of bacteriorhodopsin. This complexation is investigated in various states of hydration, in H2O and D2O, at a variety of pH levels, with mutant membranes and labeled retinals. The complexation reaction was also investigated using absorption spectroscopy and vibrational spectra using difference Fourier transform infrared spectroscopy. The results demonstrate the crucial role of water in controlling the protein conformations that lead to protein/ligand binding reactions and begin to shed new light on the protein control of a reaction that normally cannot take place in an aqueous medium. PMID- 7775445 TI - The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor. AB - Interleukin (IL)-13 elicits a subset of the biological activities of the related IL-4. The basis of this functional similarity is that their specific cell-surface receptors (called IL-13R and IL-4R) are distinct, yet are complex and share a common subunit(s). The IL-4R primary binding subunit (called IL-4R alpha) does not by itself bind IL-13. We show that the ability of IL-13 to partially compete for IL-4 binding to some human cell types depended on co-expression of IL-4R and IL-13R. However, IL-13 binding was always associated with IL-4 binding. Hyper expression of IL-4R alpha on cells expressing both IL-4R and IL-13R decreased their binding affinity for IL-4, abrogated the ability of IL-13 to compete for IL 4 binding, and yet had no effect on IL-13R properties. Anti-human IL-4R alpha monoclonal antibodies which blocked the biological function and binding of IL-4 also blocked the function and binding of IL-13. These data show that IL-4R alpha is a secondary component of IL-13R. PMID- 7775446 TI - Isolation and characterization of guamerin, a new human leukocyte elastase inhibitor from Hirudo nipponia. AB - A new human leukocyte elastase inhibitor was extracted and purified from a Korean native leech Hirudo nipponia. The inhibitor, called guamerin, has a molecular weight of 6,110 and shows inhibition constant (Ki) of 8.1 x 10(-14) M. It is stable at a wide range of pH from 1 to 11 and heat-stable up to 90 degrees C. The complete amino acid sequence of guamerin reveals a cysteine-rich polypeptide of 57 amino acid residues that shows no similarity to any known elastase inhibitors but has 51% sequence homology with hirustasin. Guamerin has identical spacing of 10 cysteine residues as antistasin-type serine proteinase inhibitors, but the P1 reactive site residue is Met36 instead of Arg. The neighboring sequence of the reactive site consists primarily of hydrophobic amino acid residues. Based on examinations of the target proteinases and the reactive site specificity, guamerin is a new low molecular weight protein that inhibits elastases. PMID- 7775447 TI - Participation and strength of interaction of lysine 95(beta) in the polymerization of hemoglobin S as determined by its site-directed substitution by isoleucine. AB - The role of Lys-95(beta), which is on the exterior of the hemoglobin (HbS) tetramer, in the aggregation process has been addressed because there is a lack of agreement on its importance. The early studies on the aggregation of HbS in the presence of other mutant hemoglobins are consistent with the subsequent electron microscopic studies in demonstrating the participation of Lys-95(beta) in gelation; the results of the crystal structure do not agree with these conclusions. Therefore, with the objective of clarifying its role we have carried out site-directed substitution of Lys-95(beta) to an isoleucine residue. The mutation was introduced by polymerase chain reaction recombination methodology, and the absence of other mutations in the beta-globin gene was established by sequencing the gene in its entirety. The recombinant mutant hemoglobin was expressed in yeast and characterized by peptide mapping and sequencing, which demonstrated that the only different tryptic peptide had the Ile substitution at position 95(beta). The recombinant hemoglobin had the correct amino acid composition and molecular weight by mass spectrometric analysis. It was also pure as judged by isoelectric focusing. It was fully functional because it had an average Hill coefficient of 3.1 and responded normally to the allosteric regulators, chloride, 2,3-diphosphoglycerate, and inositol hexaphosphate. Of particular interest was the finding that this hemoglobin mutant aggregated at a concentration of about 40 g/dl, nearly twice that at which HbS itself aggregated (24 g/dl). Therefore, Lys-95(beta) has a very important role in the aggregation process and is a good candidate site for the design of a therapeutic agent for sickle cell anemia. PMID- 7775448 TI - Temporal differences in the phosphorylation state of pre- and postsynaptic protein kinase C substrates B-50/GAP-43 and neurogranin during long-term potentiation. AB - The phosphorylation state of two identified neuralspecific protein kinase C substrates (the presynaptic protein B-50 and the postsynaptic protein neurogranin) was monitored after the induction of long term potentiation in the CA1 field of rat hippocampus slices by quantitative immunoprecipitation following 32Pi labeling in the recording chamber. B-50 phosphorylation was increased from 10 to 60 min, but no longer at 90 min after long term potentiation had been induced, neurogranin phosphorylation only at 60 min. Increased phosphorylation was not found when long term potentiation was blocked with the N-methyl-D aspartate receptor antagonist D-2-amino-5-phosphonovalerate, when only low frequency stimulation was applied or tetanic stimulation failed to induce long term-potentiation. Our data show that both B-50 and neurogranin phosphorylation are increased following the induction of long term potentiation, thus providing strong evidence for pre- and postsynaptic protein kinase C activation during narrow, partially overlapping, time windows after the induction of long term potentiation. PMID- 7775449 TI - Ligand-dependent antagonism by retinoid X receptors of inhibitory thyroid hormone response elements. AB - The role of retinoid X receptors (RXRs) on negative thyroid hormone response elements (nTREs) is not well understood. In this report, we demonstrate that an orientation-specific monomeric thyroid hormone receptor (T3R) DNA-binding site mediates thyroid hormone inhibition in the thyrotropin beta subunit gene (TSH beta) from human and murine species. Unlike positive TREs, addition of the ligand 9-cis retinoic acid (9-cis RA) to cells transfected with a T3R beta 1 expression vector significantly reduces thyroid hormone inhibition of the TSH-beta gene, indicating that endogenous retinoid receptors antagonize T3R function. Cotransfection of an RXR-alpha but not a retinoic acid receptor-alpha expression vector further antagonizes thyroid hormone inhibition, but only in the presence of 9-cis RA. Antagonism by RXR requires both an intact DNA- and ligand-binding domain. Removal of monomeric T3R binding to the TSH-beta nTRE also requires both RXR domains. A model is proposed whereby monomeric T3R is removed from a nTRE by RXR occupied by its ligand 9-cis RA. This is the first report of 9-cis RA dependent antagonism of thyroid hormone inhibition via negative TREs. PMID- 7775450 TI - Involvement of a protein distinct from transcription enhancer factor-1 (TEF-1) in mediating human chorionic somatomammotropin gene enhancer function through the GT IIC enhanson in choriocarcinoma and COS cells. AB - Previous studies suggested that transcription enhancer factor-1 (TEF-1) was involved in mediating the human chorionic somatomammotropin (hCS) gene enhancer (CSEn) function (Jiang, S.-W., and Eberhardt, N. L. (1994) J. Biol. Chem. 269, 10384-10392). We now show that an unrelated protein (CSEF-1) found in BeWo and COS-1 cells binds to the GT-IIC enhanson in CSEn and is correlated with CSEn activity in these cells. TEF-1 and CSEF-1 were distinguished by differential migration as GT-IIC complexes, thermal stability, molecular mass, and cross reactivity with chicken TEF-1 antibodies. TEF-1 and CSEF-1 bound to the GT-IIC and Sph-I/Sph-II enhansons with identical binding properties, and in vitro generated TEF-1 competed with CSEF-1 binding to the GT-IIC motif, suggesting that their actions might be mutually exclusive. Up- and down-regulation of TEF-1 levels by expression systems and antisense oligonucleotides demonstrated that TEF 1 inhibited the hCS promoter in a manner independent of the enhancer or a known TEF-1 DNA binding site. The data suggest that TEF-1 may provide a counter regulatory stimulus to the actions of CSEF-1, which may be involved in mediating enhancer stimulatory activity. PMID- 7775451 TI - Reduced chaperone-like activity of alpha A(ins)-crystallin, an alternative splicing product containing a large insert peptide. AB - alpha-Crystallin is a multimeric protein complex which is constitutively expressed at high levels in the vertebrate eye lens, where it serves a structural role, and at low levels in several non-lenticular tissues. Like other members of the small heat shock protein family, alpha-crystallin has a chaperone-like activity in suppressing nonspecific aggregation of denaturing proteins in vitro. Apart from the major alpha A- and alpha B-subunits, alpha-crystallin of rodents contains an additional minor subunit resulting from alternative splicing, alpha A(ins)-crystallin. This polypeptide is identical to normal alpha A-crystallin except for an insert peptide of 23 residues. To explore the structural and functional consequences of this insertion, we have expressed rat alpha A- and alpha A(ins)-crystallin in Escherichia coli. The multimeric particles formed by alpha A(ins) are larger and more disperse than those of alpha A, but they are native-like and display a similar thermostability and morphology, as revealed by gel permeation chromatography, tryptophan fluorescence measurements, and electron microscopy. However, as compared with alpha A, the alpha A(ins)-particles display a diminished chaperone-like activity in the protection of heat-induced aggregation of beta low-crystallin. Our experiments indicate that alpha A(ins) multimers have a 3-4-fold reduced substrate binding capacity, which might be correlated to their increased particle size and to a shielding of binding sites by the insert peptides. The structure-function relationship of the natural mutant alpha A(ins)-crystallin may shed light on the mechanism of chaperone-like activity displayed by all small heat shock proteins. PMID- 7775452 TI - New thermodynamic studies on ribonuclease A at low pH. AB - The Planck-Benzinger thermal work function, delta W zero(T), represents the heat flux term which is responsible for breaking or forming the noncovalent bonds in macro-molecular interactions, while the temperature-invariant chemical bond energy, delta H zero(T zero), gives molecules the cohesiveness to form macromolecular structures. A method is described for evaluating delta H zero(T zero) at different temperatures for ribonuclease A at low pH in the standard state, in order to determine the effect of pH on the thermodynamic stability of this protein. Ribonuclease A at pH 1.13 has a delta H zero(T zero) value of 58 kcal mol-1; at pH 2.50, delta H zero(T zero) is 58, at pH 2.77, 59, and at pH 3.15, 60 kcal mol-1. In the conformational thermal transition of ribonuclease A at pH 2.8, the compensatory temperature ranges from 50 to 320 K, and delta H zero(T zero) is approximately 5-6 kcal mol-1. This widening temperature range is typical of the unfolding process. Such differences in the magnitude of the temperature-invariant chemical bond energy can be attributed to specific changes in the solvent ordering in the immediate domain of ribonuclease A. PMID- 7775453 TI - The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. AB - The enterotoxin from Clostridium difficile (ToxA) is one of the causative agents of the antibiotic-associated pseudomembranous colitis. In cultured monolayer cells ToxA exhibits cytotoxic activity to induce disassembly of the actin cytoskeleton, which is accompanied by morphological changes. ToxA-induced depolymerization of actin filaments is correlated with a decrease in the ADP ribosylation of the low molecular mass GTP-binding Rho proteins (Just, I., Selzer, J., von Eichel-Streiber, C., and Aktories, K. (1995) J. Clin. Invest. 95, 1026-1031). Here we report on the identification of the ToxA-induced modification of Rho. Applying electrospray mass spectrometry, the mass of the modification was determined as 162 Da, which is consistent with the incorporation of a hexose into Rho. From several hexoses tested UDP-glucose selectively served as cosubstrate for ToxA-catalyzed modification. The acceptor amino acid of glucosylation was identified from a Lys-C-generated peptide by tandem mass spectrometry as Thr-37. Mutation of Thr-37 to Ala completely abolished glucosylation. The members of the Rho family (RhoA, Rac1, and Cdc42Hs) were substrates for ToxA, whereas H-Ras, Rab5, and Arf1 were not glucosylated. ToxA-catalyzed glucosylation of lysates from ToxA-pretreated rat basophilic leukemia (RBL) cells resulted in a decreased incorporation of [14C]glucose, indicating previous glucosylation in the intact cell. Glucosylation of the Rho subtype proteins appears to be the molecular mechanism by which C. difficile ToxA mediates its cytotoxic effects on cells. PMID- 7775454 TI - The influence of beta subunit structure on the interaction of Na+/K(+)-ATPase complexes with Na+. A chimeric beta subunit reduces the Na+ dependence of phosphoenzyme formation from ATP. AB - High-affinity ouabain binding to Na+/K(+)-ATPase (sodium- and potassium-transport adenosine triphosphatase (EC 3.6.1.37)) requires phosphorylation of the alpha subunit of the enzyme either by ATP or by inorganic phosphate. For the native enzyme (alpha/beta 1), the ATP-dependent reaction proceeds about 4-fold more slowly in the absence of Na+ than when saturating concentrations of Na+ are present. Hybrid pumps were formed from either the alpha 1 or the alpha 3 subunit isoforms of Na+/K(+)-ATPase and a chimeric beta subunit containing the transmembrane segment of the Na+/K(+)-ATPase beta 1 isoform and the external domain of the gastric H+/K(+)-ATPase beta subunit (alpha/NH beta 1 complexes). In the absence of Na+, these complexes show a rate of ATP-dependent ouabain binding from approximately 75-100% of the rate seen in the presence of Na+ depending on buffer conditions. Nonhydrolyzable nucleotides or treatment of ATP with apyrase abolishes ouabain binding, demonstrating that ouabain binding to alpha/NH beta 1 complexes requires phosphorylation of the protein. Buffer ions inhibit ouabain binding by alpha/NH beta 1 in the absence of Na+ rather than promote ouabain binding, indicating that they are not substituting for sodium ions in the phosphorylation reaction. The pH dependence of ATP-dependent ouabain binding in the presence or absence of Na+ is similar, suggesting that protons are probably not substituting for Na+. Hybrid alpha/NH beta 1 pumps also show slightly higher apparent affinities (2-3-fold) for ATP, Na+, and ouabain; however, these are not sufficient to account for the increase in ouabain binding in the absence of Na+. In contrast to phosphoenzyme formation and ouabain binding by alpha/NH beta 1 complexes in the absence of Na+, ATPase activity, measured as release of phosphate from ATP, requires Na+. These data suggest that the transition from E1P to E2P during the catalytic cycle does not occur when the sodium binding sites are not occupied. Thus, the chimeric beta subunit reduces or eliminates the role of Na+ in phosphoenzyme formation from ATP, but Na+ binding or release by the enzyme is still required for ATP hydrolysis and release of phosphate. PMID- 7775455 TI - Tepoxalin, a novel dual inhibitor of the prostaglandin-H synthase cyclooxygenase and peroxidase activities. AB - Prostaglandin-H synthase-1, the rate-limiting enzyme in prostaglandin synthesis, has both cyclooxygenase (CO) and peroxidase (PO) activities. While most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit only the CO activity, we describe an inhibitor, tepoxalin, that inhibits both the CO (IC50 = 0.1 microM) and the PO (IC50 = 4 microM) activities. Unlike many NSAIDs which are competitive inhibitors of CO, tepoxalin is a noncompetitive inhibitor of CO and its inhibitory effect on PO but not CO is reversed by excess heme. Moreover, inhibition of the PO activity by tepoxalin is not dependent on the enzymatic turnover of the CO activity. The hydroxamic acid of tepoxalin is responsible for the PO inhibition since a carboxylic acid derivative of tepoxalin retains full CO but not PO inhibition. We postulated that the hydroxamic group might confer the ability to inhibit PO on conventional CO inhibitors. This idea was supported by the observation that naproxen hydroxamic acid, but not naproxen showed PO inhibition. Furthermore, tepoxalin's carboxylic acid analogue and naproxen each competitively relieved PO inhibition by their respective hydroxamic acids. The intracellular activity of PO as monitored by the release of reactive oxygen species was also inhibited by both tepoxalin and naproxen hydroxamic acid. These observations suggest a strategy for design of novel compounds to inhibit prostaglandin synthase PO. The therapeutic implications of these novel PO inhibitors are discussed. PMID- 7775456 TI - A mutant at position 87 of the GroEL chaperonin is affected in protein binding and ATP hydrolysis. AB - The highly conserved aspartic acid residue at position 87 of the Escherichia coli chaperonin GroEL was mutated to glutamic acid. When expressed in an E. coli groEL mutant strain deficient for phage morphogenesis, plasmid-encoded GroEL mutant D87E restored T4 phage morphogenesis. It did not, however, reactivate the transcription of a recombinant luciferase operon from Vibrio fischeri. In vitro, GroEL mutant D87E was found to be impaired in the ability to bind nonnative proteins and to hydrolyze ATP, resulting in less efficient refolding of urea denatured ribulose-1,5-bisphosphate carboxylase/oxygenase. Mutant oligomer D87E GroEL14 was able to bind GroES7 as efficiently as wild-type GroEL14. The conserved aspartic acid residue at position 87 located in the equatorial domain of GroEL (Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D.C., Joachimiak, A., Horwich, A.L., and Sigler, P.B. (1994) Nature 371, 578-586) is thus inferred to have a dual effect on the binding of nonnative proteins to the GroEL14 core chaperonin and on ATP hydrolysis. PMID- 7775457 TI - Characterization of chitin synthase 2 of Saccharomyces cerevisiae. Implication of two highly conserved domains as possible catalytic sites. AB - Chitin synthase 2 of Saccharomyces cerevisiae was characterized by means of site directed mutagenesis and subsequent expression of the mutant enzymes in yeast cells. Chitin synthase 2 shares a region whose sequence is highly conserved in all chitin synthases. Substitutions of conserved amino acids in this region with alanine (alanine scanning) identified two domains in which any conserved amino acid could not be replaced by alanine to retain enzyme activity. These two domains contained unique sequences, Glu561-Asp562-Arg563 and Gln601-Arg602-Arg603 Arg604-Trp605, that were conserved in all types of chitin synthases. Glu561 or arginine at 563, 602, and 603 could be substituted by glutamic acid and lysine, respectively, without significant loss of enzyme activity. However, even conservative substitutions of Asp562 with glutamic acid, Gln601 with asparagine, Arg604 with lysine, or Trp605 with tyrosine drastically decreased the activity, but did not affect apparent Km values for the substrate significantly. In addition to these amino acids, Asp441 was also found in all chitin synthase. The mutant harboring a glutamic acid substitution for Asp441 severely lost activity, but it showed a similar apparent Km value for the substrate. Amounts of the mutant enzymes in total membranes were more or less the same as found in the wild type. Furthermore, Asp441, Asp562, Gln601, Arg604, and Trp605 are completely conserved in other proteins possessing N-acetylglucosaminyltransferase activity such as NodC proteins of Rhizobium bacterias. These results suggest that Asp441, Asp562, Gln601, Arg604, and Trp605 are located in the active pocket and that they function as the catalytic residues of the enzyme. PMID- 7775458 TI - Constitutive function of the basic helix-loop-helix/PAS factor Arnt. Regulation of target promoters via the E box motif. AB - Arnt is a nuclear basic helix-loop-helix (bHLH) transcription factor that, contiguous with the bHLH motif, contains a region of homology (PAS) with the Drosophila factors Per and Sim. Arnt dimerizes in a ligand-dependent manner with the bHLH dioxin receptor, a process that enables the dioxin-(2,3,7,8 tetrachlorodibenzo-p-dioxin)-activated Arnt-dioxin receptor complex to recognize dioxin response elements of target promoters. In the absence of dioxin, Arnt does not bind to this target sequence motif. The constitutive function of Arnt is presently not understood. Here we demonstrate that Arnt constitutively bound the E box motif CACGTG that is also recognized by a number of distinct bHLH factors, including USF and Max. Importantly, amino acids that have been identified to be critical for E box recognition by Max and USF are conserved in Arnt. Consistent with these observations, full-length Arnt, but not an Arnt deletion mutant lacking its potent C-terminal transactivation domain, constitutively activated CACGTG E box-driven reporter genes in vivo. These results indicate a role of Arnt in regulation of a network of target genes that is distinct from that regulated by the Arnt-dioxin receptor complex in dioxin-stimulated cells. PMID- 7775459 TI - Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. AB - The recent isolation and cloning of the G protein-coupled central cannabinoid receptor (CB1) from brain tissue has provided a molecular basis to elucidate how cannabinoid compounds may mediate their psychoactive effects. Here we report the high expression of cannabinoid receptors in human astrocytoma tumors of different grades, in the astrocytoma cell lines U373 MG and GL-15, as well as in normal astrocytes. From an analysis of the coupling mechanisms of functional CB1 receptors in U373 MG, we show that, in addition to the inhibition of adenylyl cyclase, activation by the cannabinoid agonist CP-55940 induces the expression of the immediate-early gene krox-24, also known as NGFI-A, zif/268, egr-1, and TIS8. The amount of Krox-24 protein and the level of Krox-24 DNA binding activity, as measured by Western blot and electrophoretic mobility shift assay, respectively, were also increased by the addition of CP-55940. These effects were blocked by incubation with pertussis toxin but not by treatment with hydrolysis-resistant cAMP analogues, suggesting that the transduction pathway between the cannabinoid receptor and krox-24 involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. The specific involvement of CB1 in Krox-24 induction was demonstrated in Chinese hamster ovary cells transfected with the human CB1 receptor and also in experiments using the CB1-selective cannabinoid antagonist SR 141716A. PMID- 7775460 TI - Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2a adenosine receptor. AB - The A2a adenosine receptor is a member of the G-protein coupled receptor family, and its activation stimulates cyclic AMP production. To determine the residues which are involved in ligand binding, several residues in transmembrane domains 5 7 were individually replaced with alanine and other amino acids. The binding properties of the resultant mutant receptors were determined in transfected COS-7 cells. To study the expression levels in COS-7 cells, mutant receptors were tagged at their amino terminus with a hemagglutinin epitope, which allowed their immunological detection in the plasma membrane by the monoclonal antibody 12CA5. The functional properties of mutant receptors were determined by measuring stimulation of adenylate cyclase. Specific binding of [3H]CGS 21680 (15 nM) and [3H]XAC (4 nM), an A2a agonist and antagonist, respectively, was absent in the following Ala mutants: F182A, H250A, N253A, I274A, H278A, and S281A, although they were well expressed in the plasma membrane. The hydroxy group of Ser-277 is required for high affinity binding of agonists, but not antagonists. An N181S mutant lost affinity for adenosine agonists substituted at N6 or C-2, but not at C-5'. The mutant receptors I274A, S277A, and H278A showed full stimulation of adenylate cyclase at high concentrations of CGS 21680. The functional agonist potencies at mutant receptors that lacked radioligand binding were > 30-fold less than those at the wild type receptor. His-250 appears to be a required component of a hydrophobic pocket, and H-bonding to this residue is not essential. On the other hand, replacement of His-278 with other aromatic residues was not tolerated in ligand binding. Thus, some of the residues targeted in this study may be involved in the direct interaction with ligands in the human A2a adenosine receptor. A molecular model based on the structure of rhodopsin, in which the 5' NH in NECA is hydrogen bonded to Ser-277 and His-278, was developed in order to visualize the environment of the ligand binding site. PMID- 7775461 TI - Neolactoglycosphingolipids, potential mediators of corneal epithelial cell migration. AB - Cell migration is a fundamental process of wound repair in biological systems. In an attempt to identify plasma membrane glycoconjugates which mediate cell migration, migrating and nonmigrating rabbit corneal epithelia were analyzed for reactivity with monoclonal antibodies (mAbs) specific for unsubstituted N-acetyl lactosamine (mAb 1B2), Le(x) (mAbs 7A and MMA), and sialyl Le(x) (mAb CSLEX1) carbohydrate chains of neolactoglycoconjugates. Immunohistochemical analysis indicated that regardless of whether the epithelia analyzed were from corneas of animals in vivo, corneas in organ culture, or cells in tissue culture, migrating cells stained intensely with mAb 1B2, whereas nonmigrating cells either did not stain or stained only weakly. mAbs MMA and 7A stained migrating epithelium as well as basal and middle cell layers of normal, nonmigrating epithelium. mAb CSLEX1 did not stain wounded corneas but stained the superficial cell layer of normal corneal epithelium. Biochemical analyses by TLC immunostaining revealed the presence of three mAb 1B2-reactive glycosphingolipids (GSL), neolactotetraosyl-(nLc4, paragloboside), neolactohexaosyl- (nLc6), and neolacto octaosylceramide (nLc8) in migrating epithelia. In contrast, nonmigrating epithelia contained only trace amounts of these glycolipids. Exogenous addition of nLc4, but not various other GSLs including a Le(x)-GSL (SSEA-1), stimulated re epithelialization of wounds in an experimental model of corneal epithelial wound healing. Moreover, re-epithelialization of wounds was significantly inhibited by mAb 1B2 but not by mAb MMA. The data suggest that neolacto-GSLs of corneal epithelium may be among the molecules which mediate healing of corneal epithelial wounds by influencing cell migration. PMID- 7775462 TI - Mutagenesis and the molecular modeling of the rat angiotensin II receptor (AT1). AB - The molecular interaction involved in the ligand binding of the rat angiotensin II receptor (AT1A) was studied by site-directed mutagenesis and receptor model building. The three-dimensional structure of AT1A was constructed on the basis of a multiple amino acid sequence alignment of seven transmembrane domain receptors and angiotensin II receptors and after the beta 2 adrenergic receptor model built on the template of the bacteriorhodopsin structure. These data indicated that there are conserved residues that are actively involved in the receptor-ligand interaction. Eleven conserved residues in AT1, His166, Arg167, Glu173, His183, Glu185, Lys199, Trp253, His256, Phe259, Thr260, and Asp263, were targeted individually for site-directed mutation to Ala. Using COS-7 cells transiently expressing these mutated receptors, we found that the binding of angiotensin II was not affected in three of the mutations in the second extracellular loop, whereas the ligand binding affinity was greatly reduced in mutants Lys199-->Ala, Trp253-->Ala, Phe259-->Ala, Asp263-->Ala, and Arg167-->Ala. These amino acid residues appeared to provide binding sites for Ang II. The molecular modeling provided useful structural information for the peptide hormone receptor AT1A. Binding of EXP985, a nonpeptide angiotensin II antagonist, was found to be involved with Arg167 but not Lys199. PMID- 7775463 TI - Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase. AB - Glutathionylspermidine (GSP) synthetases of Trypanosomatidae and Escherichia coli couple hydrolysis of ATP (to ADP and Pi) with formation of an amide bond between spermidine (N-(3-aminopropyl)-1,4-diaminobutane) and the glycine carboxylate of glutathione (gamma-Glu-Cys-Gly). In the pathogenic trypanosomatids, this reaction is the penultimate step in the biosynthesis of the antioxidant metabolite, trypanothione (N1,N8-bis-(glutathionyl)spermidine), and is a target for drug design. In this study, GSP synthetase was purified to near homogeneity from E. coli B, the gene encoding it was isolated and sequenced, the enzyme was overexpressed and purified in quantity, and the recombinant enzyme was characterized. The 70-kDa protein was found to have an unexpected second catalytic activity, glutathionylspermidine amide bond hydrolysis. Thus, the bifunctional GSP synthetase/amidase catalyzes opposing amide bond-forming and cleaving reactions, with net hydrolysis of ATP. The synthetase activity is selectively abrogated by proteolytic cleavage 81 residues from the C terminus, suggesting that the two activities reside in distinct domains (N-terminal amidase and C-terminal synthetase). Proteolysis at this site is facile in the absence of substrates, but is inhibited in the presence of ATP, glutathione, and Mg2+. A series of analogs was used to probe the spermidine-binding site of the synthetase activity. The activity of diaminopropane as a substrate, inactivity of the C4-C8 diaminoalkanes, and greater loss of specificity for analogs modified in the 3 aminopropyl moiety than for those modified in the 4-aminobutyl moiety indicate that the enzyme recognizes predominantly the diaminopropane portion of spermidine and corroborate N-1 (the aminopropyl N) as the site of glutathione linkage (Tabor, H. and Tabor, C. W. (1975) J. Biol. Chem. 250, 2648-2654). Trends in Km and kcat for a set of difluorosubstituted spermidine derivatives suggest that the enzyme may bind the minor, deprotonated form of the amine nucleophile. PMID- 7775464 TI - The ATP synthase gamma subunit. Suppressor mutagenesis reveals three helical regions involved in energy coupling. AB - A role in coupling proton transport to catalysis of ATP synthesis has been demonstrated for the Escherichia coli F0F1 ATP synthase gamma subunit. Previously, functional interactions between the terminal regions that were important for coupling were shown by finding several mutations in the carboxyl terminal region of the gamma subunit (involving residues at positions 242 and 269 280) that restored efficient coupling to the mutation, gamma Met-23-->Lys (Nakamoto, R. K., Maeda, M., and Futai, M. (1993) J. Biol. Chem. 268, 867-872). In this study, we used suppressor mutagenesis to establish that the terminal regions can be separated into three interacting segments. Second-site mutations that cause pseudo reversion of the primary mutations, gamma Gln-269-->Glu or gamma Thr-273-->Val, map to an amino-terminal segment with changes at residues 18, 34, and 35, and to a segment near the carboxyl terminus with changes at residues 236, 238, 242, and 246. Each second-site mutation suppressed the effects of both gamma Gln-269-->Glu and gamma Thr-273-->Val, and restored efficient coupling to enzyme complexes containing either of the primary mutations. Mapping of these residues in the recently reported x-ray crystallographic structure of the F1 complex (Abrahams, J. P., Leslie, A. G., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628), reveals that the second-site mutations do not directly interact with gamma Gln-269 and gamma Thr-273 and that the effect of suppression occurs at a distance. We propose that the three gamma subunit segments defined by suppressor mutagenesis, residues gamma 18-35, gamma 236-246, and gamma 269-280, constitute a domain that is critical for both catalytic function and energy coupling. PMID- 7775465 TI - Analysis of LE-ACS3, a 1-aminocyclopropane-1-carboxylic acid synthase gene expressed during flooding in the roots of tomato plants. AB - The plant hormone ethylene is produced in response to a variety of environmental stresses. Previous work has shown that flooding or anaerobic stress in the roots of tomato plants caused an increase in the production of the ethylene precursor 1 aminocyclopropane-1-carboxylate (ACC) in the roots, due to flooding-induced activity of ACC synthase (EC 4.4.1.14). RNA was extracted from roots and leaves of tomato plants flooded over a period of 48 h. Blot analysis of these RNAs hybridized with probes for four different ACC synthases revealed that the ACC synthase gene LE-ACS3 is rapidly induced in roots. LE-ACS2 is also induced, but at later times. The genomic clone for LE-ACS3 was isolated and sequenced. At all time points, the probe from the LE-ACS3 coding region hybridized to two bands in the RNA blots. Hybridization using the first and third introns of LE-ACS3 separately as probes indicate that flooding may inhibit processing of the LE-ACS3 transcript. Sequence homology analysis identified three putative cis-acting response elements in the promoter region, corresponding to the anaerobic response element from the maize adh1 promoter, the root-specific expression element from the cauliflower mosaic virus 35S promoter and a recognition element for chloroplast DNA binding factor I from the maize chloroplast ATP synthase promoter. PMID- 7775466 TI - Mutational analysis of Ca(2+)-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. AB - Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain of Ca2+/CaM-dependent protein kinase II interact with the catalytic core of the enzyme as a pseudosubstrate (Colbran, R. J., Smith, M. K., Schworer, C. M., Fong, Y. L., and Soderling, T. R. (1989) J. Biol. Chem. 264, 4800-4804). In the present study, we attempted to locate the pseudosubstrate motif by generation or removal of potential substrate recognition sequences (RXXS/T) at selected positions using site-directed mutagenesis. Based on previous results, Arg297, Thr305/306, and Ser314 were selected as key residues. Single mutations such as N294S, K300S, A302R, A309R, and R311A were expressed, purified, and characterized. Several of the mutants exhibited decreased binding of and activation by CaM, not surprising since the mutations were within the CaM-binding domain. None of the mutants exhibited enhanced Ca(2+)-independent kinase activity toward exogenous substrate, but the K300S and N294S mutants showed a significant enhancement in the rate and stoichiometry of 32P incorporation during Ca(2+)-independent autophosphorylation. Using two-dimensional peptide mapping and phosphoamino acid analyses, enhanced phosphorylation of the introduced Ser residue was demonstrated in the K300S mutant but not in the N294S mutant. This specific Ca(2+)-independent autophosphorylation of Ser300 is consistent with the hypothesis that Arg297 may occupy the P (-3) position in a pseudosubstrate autoinhibitory interaction with the catalytic core in the nonactivated state of the kinase. PMID- 7775467 TI - An unusually stable purine(purine-pyrimidine) short triplex. The third strand stabilizes double-stranded DNA. AB - Classical models for DNA triple helix formation assume the stabilization of these structures through the formation of Hoogsteen hydrogen bonds. This assumes that G rich duplex DNA is more stable than triplex DNA. We report the results of co migration assay, dimethyl sulfate footprint, and UV spectroscopic melting studies that reveal that at least in some cases of short (13-mer) purine(purine pyrimidine) triplex the stability of double-stranded DNA is increased by the binding of the third strand. Under conditions which are usually considered as physiological (10 mM MgCl2, 150 mM Na+ or K+) and with a rate of heating/cooling of 1 degrees C/min, there is a good reversibility of the melting profiles which is consistent with a high rate of triplex formation. Other factors than Hoogsteen hydrogen bonds should therefore be involved in triplex stabilization. We suggest that oligonucleotides with similar properties could be efficient agents for artificial gene regulation. PMID- 7775468 TI - Structural basis for species-specific differences in the phosphorylation of Na,K ATPase by protein kinase C. AB - There is considerable evidence that protein kinases play a role in regulation of the activity of the Na,K-ATPase, but the characteristics of direct kinase phosphorylation of Na,K-ATPase subunits are still not well understood. There are 36 sites that could qualify as protein kinase C motifs in rat alpha 1. Here we have used protein fragmentation with trypsin to localize the site of phosphorylation of the rat Na,K-ATPase alpha 1 subunit to within the first 32 amino acids of the N terminus and then used direct sequencing of the phosphorylated protein to determine which of two candidate serine residues was modified. The result was that at most 25% of the 32P was found on Ser-11, a site that is well conserved in Na,K-ATPase alpha 1 subunits. The remaining 75% or more of the 32P was found on Ser-18, a site that is absent in many Na,K-ATPase alpha subunit sequences. This accounts for the observation that dog and pig alpha 1 subunits can be phosphorylated by protein kinase C only to much lower levels than can rat alpha 1. It is also likely to be relevant to other known species-specific effects of protein kinase C on Na,K-ATPase. PMID- 7775469 TI - Cell type-specific secretion of parathyroid hormone-related protein via the regulated versus the constitutive secretory pathway. AB - Parathyroid hormone-related protein (PTHrP) is endoproteolytically processed to yield a family of mature secretory forms. These include an amino-terminal, a mid region, and a carboxyl-terminal form. Prior studies suggested that the mid-region form is secreted via the regulated secretory pathway, whereas the amino- and carboxyl-terminal forms are secreted via the constitutive pathway. Further, PTHrP is unusual in that it is produced under normal circumstances by neuroendocrine cell types as well as by prototypical constitutively secreting cell types. The potential for cell-specific secretory pathway use by PTHrP has not been explored. Using immunohistochemical and perifusion techniques, we demonstrate that all three PTHrP daughter peptides are secreted via the regulated pathway in neuroendocrine cells. In contrast, all three daughter peptides are secreted in a constitutive fashion by non-neuroendocrine cells. Thus, the secretion of PTHrP is unique in that it appears to be cell-specific. When it is expressed in neuroendocrine cells that contain the regulated pathway, it is secreted in a regulated fashion; when it is expressed in non-neuroendocrine cells, it defaults to the constitutive pathway. This phenomenon has not previously been described for a polypeptide hormone in naturally occurring cells. PMID- 7775470 TI - Cloning, overexpression, purification, and characterization of the carboxyl terminal nucleotide binding domain of P-glycoprotein. AB - Multidrug-resistant tumor cells overexpress P-glycoprotein (170 kDa), a member of the ABC (ATP Binding Cassette)-transporter superfamily. P-glycoprotein has been implicated in transport of a broad range of amphiphilic, hydrophobic drugs from tumor cells. The sequence and structural organization of P-glycoprotein, which consists of 12 transmembrane helices and two cytoplasmic nucleotide binding domains, is similar to other ABC-transporters. It is believed that the nucleotide binding domains of various ABC transporters, which have 30-50% sequence identity, play an important role in coupling ATP hydrolysis to the transport process. To allow structure-function studies of the nucleotide binding domains, the carboxyl terminal nucleotide binding domain (NBD) of Chinese hamster P-glycoprotein has been cloned, overexpressed, and purified both by itself and as a fusion with maltose-binding protein. It has been demonstrated that the carboxyl-terminal NBD, when overexpressed in Escherichia coli in the absence of transmembrane helices, has very low ATPase activity. This suggests that the amino-terminal nucleotide binding domain and possibly interaction with the transmembrane domains may be required for full ATPase activity. It is also consistent with the idea that the ATPase activity of P-glycoprotein is stimulated in the presence of drugs. Circular dichroism spectral analysis and the ability of carboxyl-terminal NBD, both by itself and as a fusion with maltose-binding protein, to bind ATP-agarose beads and P-glycoprotein specific monoclonal antibodies suggests that the polypeptide folds into a functional domain. Gel filtration chromatography and cross-linking studies indicate that the carboxyl-terminal NBD has a tendency to self-associate to form oligomers. It is speculated that the carboxyl-terminal NBD may play a role in self-association of P-glycoprotein molecules in the plasma membrane. PMID- 7775471 TI - Differential expression and regulation of hsp70 and hsp90 by phorbol esters and heat shock. AB - Human peripheral blood monocytes (PBM) produce superoxide anions (O2-.) by a process involving electron transfer from NADPH to O2, catalyzed by the respiratory burst enzyme NADPH oxidase. We have previously shown that phagocytosis, while activating NADPH oxidase, induced in PBM the synthesis of heat shock (HS) proteins (HSP). The present study was undertaken to establish whether this increase in HSP expression was related to O2-. and/or to classical second messengers such as protein kinase C (PKC). Thus, the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) were compared with those of heat shock on the expression, in PBM, of the major HSP, hsp70 and hsp90, using biometabolic labeling, Western and Northern blotting, and gel mobility shift assays. PMA induced the accumulation of mRNA and an increased expression of hsp90 and, to a lesser extent, hsp/hsc70 (hsc is the cognate, constitutive form). This induction was also observed in PBM from patients with chronic granulomatous disease, a genetic defect in NADPH oxidase, and was abolished by the PKC inhibitors staurosporine and H-7. PMA did not cause activation of the HS factor, and the PMA-induced overexpression expression of HSP was not blocked by the transcriptional inhibitor actinomycin D. HSP-specific mRNA stability was increased after PMA exposure as compared with heat shock. These results suggest that O2-. is not involved in the PMA-mediated induction of hsp70 and hsp90 and that, in contrast to HS, PMA increases the expression of HSP as a result of PKC induced mRNA stabilization rather than of transcriptional activation of HS genes. PMID- 7775472 TI - Artificial transmembrane segments. Requirements for stop transfer and polypeptide orientation. AB - Transmembrane segments of proteins generally consist of a long stretch of hydrophobic amino acids, which can function to initiate membrane insertion (start stop sequences), initiate translocation (signal-anchor sequences), or stop further translocation of the following polypeptide chain (stop-transfer sequences). In this study, we have taken Escherichia coli alkaline phosphatase, a transported and water-soluble protein, and examined the requirements for converting it into a transmembrane protein with particular orientation. Since the wild type enzyme is transported, there is no predisposition against membrane translocation, yet it is not a membrane protein, so it does not possess any intrinsic membrane topogenic preferences. A series of potential transmembrane segments was introduced into an internal position of the enzyme to test the ability of each to initiate translocation, stop translocation, and adopt a particular orientation. For this purpose, cassette mutagenesis was used to incorporate new structural segments composed of polymers of alanines and leucines. The threshold value of hydrophobicity required to function as a stop transfer sequence was determined. For a transmembrane segment of typical length (21 residues), this value is equivalent to the hydrophobicity of 16 alanines and 5 leucines. Interestingly, much shorter segments will also suffice to stop translocation, but these must be composed of more highly hydrophobic residues (e.g. 11 leucines). When the wild type amino-terminal signal peptide is deleted or made dysfunctional, sufficiently hydrophobic internal segments can initiate translocation of the following polypeptide and function as a signal anchor. Furthermore, in so doing, the orientation of the protein is changed from N(out) C(in) to N(in)-C(out). PMID- 7775474 TI - Nucleotide sequence and tissue-specific expression of the multifunctional protein carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) mRNA in Squalus acanthias. AB - Carbamoyl-phosphate synthetase II (CPSase II), aspartate transcarbamoylase (ATCase), and dihydroorotase (DHOase) catalyze the first three steps of de novo pyrimidine nucleotide biosynthesis, respectively. In mammalian species, these three enzyme activities exist in the cytosol in liver and other tissues as a multifunctional complex on a single polypeptide called carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) in the order of NH2 CPSase II-DHOase-ATCase-COOH. Previous studies provided evidence that in Squalus acanthias (spiny dogfish) these enzymes are not expressed in liver and that they exist as separate entities in the cytosol of extra-hepatic tissues such as testes and spleen (Anderson, P. M. (1989) Biochem. J. 261, 523-529). Here we report that the genes for these three enzymes are expressed in testes as a single transcript analogous to CAD in mammalian species and that these genes are not expressed in liver at levels that can be detected by Northern blots or by the polymerase chain reaction. The absence of the pyrimidine pathway in the liver may be related to the exclusive localization of glutamine synthetase in the mitochondrial matrix which provides for efficient assimilation of ammonia as glutamine for urea synthesis in these ureoosmotic species; thus glutamine may not be available for CPSase II or other amidotransferase activities in the cytosol. The amino acid sequence deduced from the nucleotide sequence of the shark CAD cDNA reported here is very similar to CAD from other species; alignment with the hamster CAD sequence shows 77% identical residues. PMID- 7775473 TI - Functional characterization of the promoter region of the platelet-activating factor receptor gene. Identification of an initiator element essential for gene expression in myeloid cells. AB - To understand the molecular mechanisms that direct the expression of the gene encoding the platelet-activating factor (PAF) receptor, the 5'-flanking region of the human PAF receptor gene was cloned, and its promoter activity in myeloid cell lines was characterized. By the 5'-rapid amplification of cDNA ends method and primer extension, the transcription initiation site was mapped to an adenosine residue 137 bases upstream of the ATG translation initiation codon. The promoter region lacks a typical TATA or CCAAT box. However, the sequence encompassing the transcription initiation site shows high homology to the initiator (Inr) sequence. Transfection of promonocytic U937 cells with recombinant plasmids containing a series of truncated segments of the 5'-flanking region linked to the luciferase reporter gene revealed that the sequence from nucleotides -44 to +27 relative to the transcription initiation site was sufficient to promote a high level of gene expression. The promoter activity was much lower in nonexpressing HeLa cells and promyelocytic HL-60 cells, which express relatively low levels of the PAF receptor. Gel mobility shift analysis demonstrated the binding of nuclear factors extracted from myelocytic cells to the -16/+18 sequence containing the Inr element. No binding activity was detected using the nuclear extracts from the nonmyelocytic HeLa cells. The DNA-protein complexes were sequence-specific since the binding was not significantly affected by the mutated Inr sequences or the Inr sequence of the terminal deoxynucleotidyltransferase gene. Furthermore, point mutations in the Inr element significantly reduced promoter activity in both U937 and THP-1 cell lines. When Me2SO or retinoic acid was used to induce granulocytic differentiation of HL-60 cells, a distinct Inr-protein complex was induced concurrently, but the complex was not observed in 12-O-tetradecanoylphorbol-13 acetate-induced monocytic differentiated HL-60 cells or Me2SO-induced differentiated U937 cells, indicating that the inducible Inr binding activity is granulocyte-specific. These results suggest that distinct nuclear factors interact with the unique Inr element and play a role in the transcriptional regulation of the PAF receptor in various myeloid cells. PMID- 7775475 TI - Proteolytic processing of Alzheimer's disease beta A4 amyloid precursor protein in human platelets. AB - The processing of amyloid precursor protein (APP) and production of beta A4 amyloid are events likely to influence the development and progression of Alzheimer's disease, since beta A4 is the major constituent of amyloid deposited in this disorder. Our previous studies showed that human platelets contain full length APP (APPFL) and are a suitable substrate to study normal APP processing. In the present study, we show that a 22-kDa beta A4-containing carboxyl-terminal fragment (22-CTF) of APP is present in unstimulated platelets. Both APPFL and 22 CTF are proteolytically degraded when platelets are activated with thrombin, collagen, or calcium ionophore A23187. Complete cleavage of APPFL and 22-CTF require the presence of extracellular calcium. Following stimulation in the presence of calcium, a new CTF of 17 kDa is generated, and the NH2-terminal epitope of beta A4 amyloid is lost. Preincubation of platelets with the cell permeable cysteine protease inhibitors calpeptin, (2S,3S)-trans-epoxysuccinyl-L leucyl-amido-3-methylbutane ethyl ester (E64d), Na alpha-p-tosyl-L-lysine chloromethyl ketone, or calcium chelator EGTA before platelet stimulation inhibits the degradation of both APPFL and 22-CTF. Divalent metal ions including zinc, copper, and cobalt inhibit the degradation of APPFL and 22-CTF. This study suggests that a calcium-dependent neutral cysteine protease is involved in the proteolytic processing of an amyloidogenic species of APP in human platelets. PMID- 7775476 TI - Identification of the primase active site of the herpes simplex virus type 1 helicase-primase. AB - Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase-primase composed of the products of the three DNA replication-specific genes UL5, UL8, and UL52 (Crute, J. J., and Lehman, I. R. (1991) J. Biol. Chem. 266, 4484-4488). The UL5 and UL52 products constitute a heterodimeric subassembly of the holoenzyme that contains both helicase and primase activities (Calder, J. M., and Stow, N. D. (1990) Nucleic Acids Res. 18, 3573-3578; Dodson, M. S., and Lehman, I. R. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 1105-1109). The role of the UL52 product in the active HSV-1 helicase-primase was examined. A sequence located between residues 610 and 636 on the UL52 protein was found to be conserved among the UL52 homologues of eight herpesviruses. The carboxyl-terminal portion of this conserved sequence consisted of two Asp residues separated by a variable hydrophobic amino acid residue and is analogous to the divalent metal-binding site of DNA polymerases and several DNA primases. This motif has been designated the herpesvirus primase DXD motif. To study the role of the HSV-1 primase DXD motif in primase action, three site-directed changes were introduced into the UL52 gene. The helicase activity of the recombinant holoenzymes was unaffected by any of the introduced changes. Changing either of the two Asp residues that constitute the divalent metal-binding site (Asp628 or Asp630) to Ala dramatically reduced the primase activity of the HSV-1 helicase-primase holoenzyme in vitro, whereas alteration of the nearby conserved residue Asn624 to Gly had minimal effect. Therefore, in the three-subunit HSV-1 helicase-primase, the UL52 product provides at least a part of the primase catalytic site. PMID- 7775477 TI - The responsiveness of a tetracycline-sensitive expression system differs in different cell lines. AB - A tetracycline-sensitive inducible expression system was used to regulate the expression of neurotransmitter receptor genes in two mammalian cell lines. The dopamine D3-receptor was stably expressed in GH3 cells, and GluR6 (a glutamate receptor subunit) was stably expressed in human embryonic kidney (HEK 293) cells. Three striking differences were found. 1) In the inactive state, virtually no D3 receptor expression was found in GH3 cells, whereas substantial levels of GluR6 expression were found in HEK 293 cells. 2) The induction of expression obtained upon removal of tetracycline was robust in GH3 cells but only modest in HEK 293 cells. 3) Whereas in each clonal cell line, the expression of a co-transfected hybrid transactivator is clearly regulated in a tetracycline-responsive manner, in the induced state, its mRNA levels were found to be very low in GH3 cells and very high in HEK 293 cells. The results indicate that, in contrast to GH3 cells, HEK 293 cells do not provide a cellular environment in which the expression of a heterologous gene can be tightly controlled in a tetracycline-responsive manner. PMID- 7775478 TI - G2/M transition requires multisite phosphorylation of oncoprotein 18 by two distinct protein kinase systems. AB - Oncoprotein 18 (Op18) is a conserved cytosolic protein that is a target for both cell cycle and cell surface receptor-regulated phosphorylation events. The four residues Ser16, Ser25, Ser38, and Ser63 are all subject to cell cycle-regulated phosphorylation. Ser25 and Ser38 are targets for cyclin dependent kinases (CDKs), while Ser16 and Ser63 are phosphorylated by an unidentified protein kinase. We have recently shown that induced expression of a CDK target site-deficient mutant, Op18-S25A,S38A, blocks human cell lines during G2/M transition. In the present report we show that mitosis is associated with complete phosphorylation of the two Op18 CDK target sites Ser25 and Ser38 and that Ser16 and Ser63 are also phosphorylated to a high stoichiometry. To evaluate the function of multisite phosphorylation of Op18, we expressed and analyzed the cell cycle phenotype of different kinase target site-deficient mutants. The data showed that induced expression of the S16A,S63A, S25A,S38A, and S16A,S25A,S38A,S63A mutants all resulted in an indistinguishable phenotype, i.e. immediate G2/M block and subsequent endoreduplication, a given fraction of G2 versus M-phase blocked cells, and a characteristic nuclear morphology of M-blocked cells. This result was unexpected; however, a likely explanation was provided by analysis of Op18 phosphoisomers, which revealed that mutations of the CDK sites interfere with phosphorylation of Ser16 and Ser63. The simplest interpretation of our results is that phosphorylation of Ser16 and Ser63 is essential during G2/M transition and that the phenotype of the S25A,S38A mutant is mediated by the observed block of Ser16/Ser63 phosphorylation. PMID- 7775479 TI - Cloning of a novel phosphoprotein regulated by colony-stimulating factor 1 shares a domain with the Drosophila disabled gene product. AB - A unique protein with an apparent molecular mass of 96 kilodaltons (p96) was detected in the murine macrophage cell line, BAC1.2F5. The murine cDNA encoding p96 was cloned and sequenced, along with cDNAs representing two alternatively spliced forms of the protein. All three proteins possessed identical amino terminal domains with significant similarity to the amino-terminal domain of the Drosophila disabled gene product and carboxyl-terminal domains containing proline rich sequences characteristic of src homology region (domain 3) binding regions. BAC1.2F5 cells predominantly expressed the p96 protein, although mRNA and protein corresponding to the p67 splice variant were also detected. Electrophoretic gel retardation of p96 in response to stimulation of the cells with colony stimulating factor 1 was noticeable within 5 min after growth factor addition and reached a maximum at 60 min. Metabolic labeling experiments showed that the gel retardation of p96 was associated with increased phosphorylation of the protein exclusively on serine residues. These data identify a novel protein that is phosphorylated in response to mitogenic growth factor stimulation. PMID- 7775480 TI - The BM88 antigen, a novel neuron-specific molecule, enhances the differentiation of mouse neuroblastoma cells. AB - The BM88 antigen is a neuron-specific molecule widely distributed in the mammalian nervous system. It is a 22-kDa, apparently not glycosylated, integral membrane protein, which appears early during brain development and remains at high levels in the mature animal. Here, we describe the cDNA cloning of the porcine BM88 antigen and present evidence that this protein is involved in neuroblastoma cell differentiation. The deduced protein is a novel molecule consisting of 140 amino acids and bears a putative transmembrane domain at the COOH-terminal region. The mRNA of this protein is expressed only in neural tissues, where it is restricted to neurons. Stably transfected Neuro-2a cells overexpressing the BM88 antigen exhibited a significant change in morphology, reflected by enhanced process outgrowth, and a slower rate of division. Moreover, in the presence of differentiation agents, such as sucrose and retinoic acid, an accelerated differentiation of the transfected Neuro-2a cells was observed. Especially in the presence of sucrose, the consequent overexpression of the BM88 antigen in the transfected cells resulted in their enhanced morphological differentiation accompanied by the induction of neurofilament protein expression. Our results suggest that the BM88 antigen plays a role in the differentiation of neuroblastoma cells. PMID- 7775481 TI - Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine rich region. AB - The Ras-related nuclear protein, Ran, has been implicated in nuclear transport. By screening a HeLa cell lambda expression library with Ran-GTP and sequencing overlapping cDNA clones, we have obtained the derived primary structure of a protein with a calculated molecular mass of 358 kDa. Using antibodies raised against an expressed segment of this protein, we obtained punctate nuclear surface staining by immunofluorescence microscopy that is characteristic for nucleoporins. Electron microscopy of immunogold-decorated rat liver nuclear envelopes sublocalized the 358-kDa protein at (or near) the tip of the cytoplasmic fibers of the nuclear pore complex (NPC). In agreement with current convention, this protein was therefore termed Nup358 (for nucleoporin of 358 kDa). Nup358 contains a leucine-rich region, four potential Ran binding sites (i.e. Ran binding protein 1 homologous domains) flanked by nucleoporin characteristic FXFG or FG repeats, eight zinc finger motifs, and a C-terminal cyclophilin A homologous domain. Consistent with the location of Nup358 at the cytoplasmic fibers of the NPC, we found decoration with Ran-gold at only the cytoplasmic side of the NPC. Thus, Nup358 is the first nucleoporin shown to contain binding sites for two of three soluble nuclear transport factors so far isolated, namely karyopherin and Ran-GTP. PMID- 7775482 TI - Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. AB - To determine the mechanism(s) by which the endogenous mediator nitric oxide (NO) inhibits the activation of transcription factor NF-kappa B, we stimulated human vascular endothelial cells with tumor necrosis factor-alpha in the presence of two NO donors, sodium nitroprusside and S-nitrosoglutathione. Electrophoretic mobility shift assays demonstrated that both NO donors inhibited NF-kappa B activation by tumor necrosis factor-alpha. This effect was not mediated by guanylyl cyclase activation since the cGMP analogue 8-bromo-cGMP had no similar effect. Inhibition of endogenous constitutive NO production by L-N monomethylarginine, however, activated NF-kappa B, suggesting tonic inhibition of NF-kappa B under basal conditions. NO had little or no effects on other nuclear binding proteins such as AP-1 and GATA. Immunoprecipitation studies showed that NO stabilized the NF-kappa B inhibitor, I kappa B alpha, by preventing its degradation from NF-kappa B. NO also increased the mRNA expression of I kappa B alpha, but not NF-kappa B subunits, p65 or p50, and transfection experiments with a chloramphenicol acetyltransferase reporter gene linked to the I kappa B alpha promoter suggested transcriptional induction of I kappa B alpha by NO. We propose that the induction and stabilization of I kappa B alpha by NO are important mechanisms by which NO inhibits NF-kappa B and attenuate atherogenesis. PMID- 7775484 TI - Human dual specificity phosphatase VHR activates maturation promotion factor and triggers meiotic maturation in Xenopus oocytes. AB - Bacterially expressed, dual specificity phosphatase VHR protein induced germinal vesicle breakdown (GVBD) when microinjected into Xenopus oocytes, albeit with slower kinetics than that observed in progesterone- or insulin-induced maturation. A mutant VHR protein missing an essential cysteine residue for its in vitro phosphatase activity completely lacked activity in injected oocytes. VHR injection done in conjunction with progesterone or insulin treatment resulted in highly synergized GVBD responses showing much faster kinetics than that produced by VHR or either hormone alone. The delayed kinetics of VHR-induced GVBD and the synergistic responses obtained in the presence of hormones suggested that this protein may be promoting G2/M transition by weakly mimicking the action of cdc25, the dual specificity phosphatase that physiologically activates the maturation promotion factor. Various experimental observations are consistent with such a role for the injected VHR in oocytes: 1) as opposed to hormone-treated oocytes, histone H1 kinase activation is not preceded by MAPK activation in the process of GVBD in VHR-injected oocytes; 2) incubation of purified VHR with highly concentrated cell-free extracts of untreated oocytes resulted in activation of histone H1 kinase activity in the lysates; 3) coinjection of VHR with activated Ras proteins resulted in synergized responses, faster than those produced by either protein alone; 4) coinjection of VHR with the purified amino-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (which blocks insulin induced GVBD) does not affect VHR-induced maturation. The biological actions of VHR in oocytes clearly distinguish it from other dual specificity phosphatases, which have shown inhibitory effects when tested in oocytes. We speculate that VHR may represent a dual specificity phosphatase responsible for activation of cdk cyclin complex(es) at a still undetermined stage of the cell cycle. PMID- 7775483 TI - Production of human secretory component with dimeric IgA binding capacity using viral expression systems. AB - The cDNA encoding the NH2-terminal 589 amino acids of the extracellular domain of the human polymeric immunoglobulin receptor was inserted into transfer vectors to generate recombinant baculo- and vaccinia viruses. Following infection of insect and mammalian cells, respectively, the resulting truncated protein corresponding to human secretory component (hSC) was secreted with high efficiency into serum free culture medium. The Sf9 insect cell/baculovirus system yielded as much as 50 mg of hSC/liter of culture, while the mammalian cells/vaccinia virus system produced up to 10 mg of protein/liter. The M(r) of recombinant hSC varied depending on the cell line in which it was expressed (70,000 in Sf9 cells and 85 95,000 in CV-1, TK- 143B and HeLa). These variations in M(r) resulted from different glycosylation patterns, as evidenced by endoglycosidase digestion. Efficient single-step purification of the recombinant protein was achieved either by concanavalin A affinity chromatography or by Ni(2+)-chelate affinity chromatography, when a 6xHis tag was engineered to the carboxyl terminus of hSC. Recombinant hSC retained the capacity to specifically reassociate with dimeric IgA purified from hybridoma cells. PMID- 7775486 TI - A dynamic shoulder model: reliability testing and muscle force study. AB - This study introduces a dynamic shoulder model, where forces were applied to individual muscles in ten cadaveric specimens. The model provided reproducible glenohumeral joint motion and thereby allowed the investigation of active, glenohumeral joint mechanics. Forces were created by servo-actuated hydrodynamic cylinders and applied to the deltoid muscle and to the rotator cuff through wire cables. Computerized regulation initiated precise, time controlled cycles of glenohumeral joint motion. The position of the glenohumeral joint in all spatial orientations was measured and recorded using an ultrasonic sensor device. Reproducibility of glenohumeral joint motion was demonstrated on the basis of five cycles of glenohumeral joint elevation. Repeatability variance of position measurements for five cycles of elevation averaged 0.80 degrees for abduction, 0.75 degrees for anteflexion and 1.36 degrees for internal rotation. Arm weight and force distribution at the shoulder musculature were estimated according to the literature. In comparison to estimated physiologic conditions, a one third increase of arm weight led to a significant (p < 0.05) decrease of elevation of 20%, a one third decrease of arm weight to an average increase of elevation of 18% (p < 0.05). Exclusion of the supraspinatus muscle caused a significant (p < 0.05) 6% decrease of elevation of the glenohumeral joint. Without force applied to the subscapularis and infraspinatus/teres minor muscles, elevation decreased 16% (p < 0.05). A decrease of glenohumeral joint elevation of 25% resulted when force was applied to the deltoid muscle alone (p < 0.05). PMID- 7775485 TI - Differential regulation of a multipromoter gene. Selective 12-O tetradecanoylphorbol-13-acetate induction of a single transcription start site in the HMG-I/Y gene. AB - The human HMG-I/Y gene, encoding the non-histone "high mobility group" proteins HMG-I and HMG-Y, is transcriptionally activated in human K562 erythroleukemia cells by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA treatment induces differentiation of K562 cells within 2-4 days after treatment. In this report, we show that transcriptional activation of the HMG-I/Y gene is dependent on protein synthesis and is an early event (2 h after induction) in the TPA mediated differentiation process. Of the four functional transcription start sites present in the gene, only one (start site 2) is preferentially induced upon TPA treatment. This is the first report, to our knowledge, of the preferential utilization of a specific transcription start site in response to a particular stimulus in a gene that contains multiple promoters. This indicates that each start site in the gene has the potential to be independently regulated instead of being coordinately controlled as shown in a number of other genes. In addition, sequences upstream of the inducible start site, which contains a TPA-responsive element, mediates TPA inducibility through AP1 (or an AP1-like) transcription factor. The HMG-I/Y proteins function as key regulators of gene expression and play a significant role in chromatin structural changes as well. The cloning and sequence analyses previously reported indicated the structure of the HMG-I/Y gene to be highly complex and predicted its expression to be tightly regulated. The results presented here confirm and extend these earlier findings. PMID- 7775487 TI - Identification of elastic properties of homogeneous, orthotropic vascular segments in distension. AB - Characterization of the constitutive behavior of normal and pathological blood vessel segments could provide the clinician with a means to predict the onset and assess the severity of certain vascular maladies. Many of the constitutive models that have been proposed to date either fail to properly consider certain features of the anatomic structure and function of vascular tissue or are so mathematically complex that their utilization is intractable. We have developed a material identification technique that first required the adaptation and validation of a constitutive law describing the nonlinear, three-dimensional behavior of orthotropic, compressible, hyperelastic vascular segments. By coupling a nonlinear finite element program and experimental data with a robust nonlinear least-squares regression algorithm, a set of elastic parameters (moduli) is obtained. Regressions on data for a canine carotid artery and rabbit infrarenal aorta yielded coefficients of variation of 0.21 and 0.08, respectively. The estimated moduli demonstrated certain trends found by other investigators: both the canine carotid artery and rabbit aorta were found to be stiffer radially than circumferentially, and the former was found to be stiffer circumferentially than longitudinally. Using these material constants and measured arterial pressures, the stress distribution was computed for each specimen. The predicted radial stress was consistent with a transmural variation of approximately--p (applied luminal pressure) to approximately zero in both specimens, while the circumferential stresses ranged from 2.2p to 0.7p for the canine carotid, and from 6.4p to 3.7p for the rabbit aorta. The stress distributions qualitatively agreed with those reported in previous investigations, as well as with certain physiologic observations. Based on the results of our two sample cases, we believe that our technique could be beneficial to the assessment of the three-dimensional, anisotropic behavior of vascular tissue. PMID- 7775488 TI - Variation of muscle moment arms with elbow and forearm position. AB - We hypothesized that the moment arms of muscles crossing the elbow vary substantially with forearm and elbow position and that these variations could be represented using a three-dimensional computer model. Flexion/extension and pronation/supination moment arms of the brachioradialis, biceps, brachialis, pronator teres, and triceps were calculated from measurements of tendon displacement and joint angle in two anatomic specimens and were estimated using a computer model of the elbow joint. The anatomical measurements revealed that the flexion/extension moment arms varied by at least 30% over a 95 degrees range of motion. The changes in flexion/extension moment arm magnitudes with elbow flexion angle were represented well by the computer model. The anatomical studies and the computer model demonstrate that the biceps flexion moment arm peaks in a more extended elbow position and has a larger peak when the forearm is supinated. Also, the peak biceps supination moment arm decreases as the elbow is extended. These results emphasize the need to account for the variation of muscle moment arms with elbow flexion and forearm position. PMID- 7775489 TI - The effect of strict muscle stress limits on abdominal muscle force predictions for combined torsion and extension loadings. AB - The objective of this study was to determine to what extent the central nervous system activates torso muscles so as to equalize the largest muscle stresses. Two optimization models that treat large muscle stresses differently were formulated. One model minimized spinal compression force subject to the lowest possible muscle stress limit, and the other model minimized the sum of cubed muscle stresses. Experimental conditions were determined for which the two models made different muscle force predictions. Specifically, the models predicted different rectus abdominis activity levels for tasks involving torsion and extension moment loadings. Surface electromyography was used to evaluate the model predictions. Applied loads were chosen to assure that the rectus abdominis EMG exceeded 30% MVC. Analysis of variance indicated that rectus abdominis activity was not affected by torsion loading at the p < 0.05 level of significance in a statistical design having 90% power, which was consistent with the predictions of the model that minimized the sum of cubed muscle stresses. Thus, it was concluded that equalization of the largest muscles stress was not the paramount objective of the central nervous system in the tasks studied. PMID- 7775490 TI - Is staircase walking a risk for the fixation of hip implants? AB - Considerable forces and moments act at hip prostheses during most kinds of physical activities. High torque around the stem axis may contribute to implant loosening. With instrumented hip prostheses the joint force and its direction, the bending moment in the frontal plane and the torque were measured in two patients during upstairs, downstairs and level walking. The data give information on whether or not stairclimbing causes a more severe loading situation for the implants than walking. While going upstairs at normal speed the joint force is 10% higher than during walking at 3 km h-1. Downstairs it increases by 20%. The bending moments change by nearly the same amounts. Upstairs the torsional moment is about twice as high as during slow walking. But walking at 5 km h-1 or slow jogging causes forces and moments of similar magnitudes. Even higher loads were observed when the patients stumbled without falling. Although torque during staircase walking is high, extreme values exclusively during stairclimbing are not confirmed by our data. The torsional moments now observed in vivo are close to or even exceed the experimentally determined limits of the torsional strength of implant fixations, found in the literature. Obviously, torsional moments play an important role for the potential loosening of hip prostheses. PMID- 7775492 TI - Mechanics of wave reflections in a coronary bypass loop model: the possibility of partial flow cut-off. AB - Local hemodynamics in a bypass loop model with dimensions typical of those in the human coronary circulation are studied, particularly with regards to the effects of wave reflections. While in a single vessel of such dimensions and a single source of wave reflections the effects would be insignificant, in a bypass loop the combination of a narrowed vessel with a converging junction and several reflection sites may produce wave reflections with significant effects on the pressure and flow distributions within the vessels forming the loop. Calculations to test this possibility were performed, based on D'Alembert's solutions of the wave equation and with a proposed matching scheme to deal with the converging junction. The results indicate that there are very large wave reflection effects at a frequency of 10 Hz, smaller but significant effects at 5 Hz, and some insignificant effects at 1 Hz. The results also indicate that partial flow cut off may occur within the loop under some singular circumstances, whereby certain harmonic components of the incident wave are totally reflected. In the clinical setting these effects would detract from the efficiency of the bypass as a conduit, to a degree dependent on the degree of occlusion of the bypassed vessel. The choice of a larger diameter for the bypass appears to diminish this dependence and is thus on the whole favorable despite the contribution it makes to impedance mismatch at the junction. PMID- 7775491 TI - Load-sharing patterns in the shoulder during isometric flexion tasks. AB - Patterns of load-sharing between the shoulder muscles during isometric flexion tasks were studied by using both a biomechanical shoulder model and electromyographic (EMG) recordings of ten subjects. The effect of changes in several model parameters and shoulder stiffness constraints on the predicted load sharing patterns were studied, while the arm position, hand load and precision requirements of the tasks were varied. The results calculated using the model were, when compared to the EMG recordings, plausible predicting a high level of synergistic contraction of muscles of the shoulder muscles during flexion tasks. The trends of the model-predicted muscle forces corresponded well to the EMG recordings. At low hand load levels the increasing of the shoulder stiffness strongly increased the muscle force levels, thus increasing also the level of synergistic contraction of muscles. At higher load levels the increase in the muscle forces was not so high, because the model predicted a high level of simultaneous contraction of muscles already at a low level of shoulder stiffness. Cluster analysis of the EMG recordings revealed large inter-individual differences in the load distribution patterns during flexion tasks. The constraint angle of the glenohumeral joint contact force direction was found to be an important model parameter affecting both the predicted forces and the maximum force production ability of the shoulder. PMID- 7775493 TI - Stress protection due to external fixation. AB - Bone is sensitive to mechanical influences. The presence of an orthopaedic device will impose constraints on the mechanical environment that may influence subsequent remodelling and repair. An Oxford External Fixator was applied to six intact ovine tibiae. The strains engendered during normal walking were then recorded from strain gauges applied to the mid-shaft of the bone. The fixator configuration was then altered such that the intact fixator bar connecting the pins was replaced with a sectioned version that did not permit load transfer through the fixator, and the strain environment re-recorded. The peak strains recorded with the intact bar were significantly lower than those recorded with the sectioned bar. This showed that the use of a fixator with an intact bar resulted in significant stress protection of the underlying bone. A fixator was then applied to both the right and left tibiae of a further six animals and the resulting strain environment and corresponding remodelling response was observed over 16 weeks. In each case one fixator was configured with an intact bar (the stress protected limb), whilst the other utilised a sectioned bar (the unprotected limb). The results showed that over this period the bone mineral content fell by 9% in the stress protected limb compared to the unprotected limp. Quantitative assessment of the bones showed that this bone loss occurred as a direct consequence of resorption on the periosteal and endosteal surfaces. In addition, strain recordings at week 16 showed that the fixator was still stress protecting the tibia. PMID- 7775495 TI - Time-frequency analysis of postural sway. AB - Postural sway during quiet stance has been used to characterize the postural control system. Most studies have used center of pressure (COP) measurements and have assumed stationarity, however, recent research has indicated that COP is not stationary. The purpose of this study is to introduce and demonstrate a nonstationary spectral estimation technique to examine the time-varying nature of postural sway. Data from two experiments were used to verify the usefulness of the spectral estimator for the analysis of COP. The first data set contains COP recorded from normal subjects swaying about their ankles in response to a metronome as it was gradually changed from 2 to 1 Hz. The time-frequency distribution reveals time-varying spectral changes corresponding to frequency changes made by the subjects. The second set consists of COP from normal subjects and vestibularly impaired patients standing quietly on a force plate with eyes closed for 100 s. The time-frequency distributions for the COP were estimated for both sets of data. The COP's appear to be nonstationary with the energies at a given frequency modulating through time. PMID- 7775494 TI - Force and pressure transmission through the normal wrist. A theoretical two dimensional study in the posteroanterior plane. AB - Force transmission through the wrist in the normal population was investigated using the rigid body spring modeling (RBSM) technique (assuming carpal bones are rigid bodies interposed by series of springs simulating articulating cartilage and constraining ligaments). One-hundred and twenty normal wrist posteroanterior X-rays of adults (evenly divided to represent both genders and two age groups) provided the anatomical data. Reaction forces between the carpal bones were modeled using a system of compression linear springs, representing cartilage and subchondral bone, and of tensile linear springs, representing ligaments. The spring constants were determined based on the material properties of wrist cartilage and ligaments. Assumed axial loads were applied along the metacarpals to simulate a grasp strength of 10 N with active stabilization of the wrist in neutral position. The force transmission ratio at the radio-ulno-carpal joint was 55% through the radio-scaphoid and 35% through the radio-lunate joints. The remaining 10% of the load was passing through the triangular fibrocartilage with minor differences between genders. Among the intercarpal joints, a large percentage of the load of the wrist was transmitted to the scaphoid. The peak pressure was highest at the proximal pole of the radio-scaphoid, with a radio scaphoid versus radio-lunate peak pressure ratio of 1.6. The most important ligaments in terms of load transmission were those opposing ulnar translation of the carpus. The wrist morphology had little influence on the magnitude and pattern of load distribution. There was no effect of age on wrist force distribution. PMID- 7775496 TI - Use of the boundary element method for biological morphometrics. AB - Tensorial morphometric assessments of form difference can aid in the understanding of the cause of the form difference by providing reference frame independent, anisotropic, non-homogenous descriptions. The majority of biological and prosthetic structures cannot be adequately analyzed by current methods due to the paucity of anatomical landmarks and methodological requirements of subdivision through the domain. Internal subdivisions can be eliminated with the boundary element method (BEM). A non-landmark (NL) method can be developed by the combination of elliptical Fourier analysis (EFA) and BEM. The appropriateness of NL and BEM was investigated. The growth of the female rat neural skull from 7 to 14 postnatal days was calculated with respect to increase in area. Linear and quadratic BEM landmark analysis were made using 10 and 5 elements, respectively. Five hundred linear BEM elements were constructed from the EFA equations for NL. The form change tensors were obtained by the solution of the Laplace equation using boundary displacements as the essential boundary conditions. For comparison, simplex triangular finite element analysis (FEA), quadrilateral FEA and macroelement analysis were made on the same structure. Results correspond well to the two major growth process in this time period; (1) high cerebellar growth, and (2) relatively higher facial versus neural growth. The results in other regions are close to the biologically observed 36% increase in area. The average difference between BEM, NL versus FEA is 1.9 and 2.8%. Trends in results with position are almost identical for BEM, NL, MEM and quadrilateral FEA. The morphometric landmark BEM technique requires an additional numerical scheme to eliminate the singularities near the boundary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775497 TI - Influence of thigh muscles on the axial strains in a proximal femur during early stance in gait. AB - This work is focused on the in vitro simulation of the loads occurring in the femur during early stance in gait, for hip prosthesis stress shielding test purposes. Ten thigh muscles (the three gluteal muscles, the three vasti, rectus femoris, adductor longus and magnus, biceps femoris), simulated by nylon straps, were tested in order to establish their influence on the strains in the proximal femur. Axial and hoop strains were recorded from 16 strain gauges for the effect of each muscle and compared to the strains recorded as a result of the hip joint reaction force only (i.e. without muscle simulation). It appears that the three glutei are the principal muscles in determining the vertical strains, however the rectus femoris, biceps femoris and the adductors were also seen to significantly affect the strain pattern. The inadequacy of increasing the adduction angle and applying the resultant force at the hip joint to simulate the abductors was also confirmed. PMID- 7775498 TI - Resonant frequency of a pin-accelerometer system mounted in bone. AB - Invasive measurements of spinal motion using intraosseous metal pins have become common. For this reason, the resonant frequency of intraosseous pins attached with accelerometers was determined using two different methods. It was concluded that plucking the pin is a reliable method for determining the resonant frequency and, in order to accurately measure bone movement at frequencies up to 32 Hz, the pin diameter should be 2.0 mm or more. With a mass of the accelerometer assembly equal to 27 g, the total pin length should not exceed 80 mm with a bone accelerometer distance of 25 mm and a pin diameter of 2.4 mm. PMID- 7775499 TI - Freeze clamping musculo-tendinous junctions for in vitro simulation of joint mechanics. AB - Incorporation of physiologic muscle tensions to simulate normal in vivo joint loading in cadaveric biomechanical studies has been a challenging problem, especially about the knee, foot, and shoulder. Simulation of muscle contraction requires attachment of tension producing devices to musculotendinous units. To this end, we modified the 'cryo-jaw' device, first described by Riemersma and Schamhardt (1982, J. Biomechanics 15, 619-620) to couple linear actuators to fresh cadaver tendons. These clamps were used in the simulation of 11 different muscles in laboratory investigations of shoulder, elbow, knee, and foot function. The clamps were able to transmit repetitively 3500 N of quadriceps force in eight knees and 2000 N of Achilles force in 11 feet. Overall success rate was 95%. PMID- 7775500 TI - Longitudinal strain of canine and porcine aortas. AB - The in situ longitudinal strain of canine and porcine aortas was investigated. Marks of black water-resistant ink were placed on the aortas and the axial lengths between the marks were measured in situ and in vitro. When the aortas were cut, the retraction was measured and described by the stretch ratio, which is defined as the length of a segment in situ divided by the length at no-load state. Results show that the stretch ratios of both porcine and canine aortas increase monotonically from 1.2 in the descending region to about 1.5 in abdominal region. Species differences are seen in the middle region. In both animals, the stretch ratio is correlated to the cross-sectional area of the vessel wall. PMID- 7775501 TI - Comments on 'Relationship between ankle muscle and joint kinetics during the stance phase of locomotion in the cat'. PMID- 7775502 TI - Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat. AB - Oxidants are released directly from smoke and also as a result of the airways inflammation that occurs after smoke injury. We determined the relation between the degree of tissue oxidant change with the use of malondialdehyde content to measure lipid peroxidation and the degree of lung and systemic organ damage and resulting damage mortality 24 hours after a controlled smoke exposure in a rat model. We also monitored changes in the key tissue antioxidant catalase. We found that the degree of lung lipid peroxidation and the decrease in catalase activity directly correlated with mortality caused by respiratory failure and with the degree of lung inflammation but that they did not correlate with the peak carboxyhemoglobin level, a marker of smoke gas phase exposure. The lung oxidant changes also directly correlated with increased systemic lipid peroxidation and decreased catalase in liver and kidney tissue. We conclude that the initial smoke insult causes lung and in turn systemic inflammation with resulting release of oxidants, which leads to tissue oxidant injury. The degree of lung oxidant change significantly correlates with the degree of lung tissue injury, respiratory failure, and mortality, and the major source of the oxidant changes is tissue inflammation rather than oxidants in the smoke itself. PMID- 7775503 TI - Superoxide dismutase and leupeptin prevent delayed reperfusion injury in the rat small intestine during burn shock. AB - Delayed fluid resuscitation during burn shock is thought to compromise the integrity of gut mucosa and allow enteric bacteria to cross the luminal wall and infect other sterile organ systems. Superoxide dismutase, a free-oxygen radical scavenger; leupeptin, a protease inhibitor; and verapamil, a calcium channel blocker, were studied to evaluate their efficacy in maintaining cellular integrity in the gut of thermally burned rats whose fluid resuscitation had been delayed. Fifty male rats weighting 280 to 320 gm were given a full-thickness scald burn covering 50% total body surface area. Ten received early fluid resuscitation beginning half an hour after burn, and 40 received fluid resuscitation delayed by 6 hours. Those receiving delayed resuscitation were given superoxide dismutase (n = 10), leupeptin (n = 10), verapamil (n = 10), or a placebo of normal saline solution (n = 10) at the time of fluid resuscitation. Ileal mucosa samples were harvested, and adenosine triphosphate, diphosphate, and monophosphate were measured. Adenosine triphosphate, total nucleotides, and energy charge potential were significantly lower in the placebo group without therapy compared with those of the early resuscitation group. Superoxide dismutase and leupeptin therapy prevented this drop in cellular energy. Total water content was significantly increased in the placebo group compared with that of the early resuscitation group; superoxide dismutase was able to prevent this increase. Data indicate that intestinal reperfusion injury in burned rats can be effectively modulated with superoxide dismutase or leupeptin therapy. PMID- 7775505 TI - Translocation and survival of Bacteroides fragilis after thermal injury. AB - B. fragilis and E. coli were labeled with tritiated (3H) thymidine, and 10(10) of each were given separately by gavage in Balb/c mice immediately before a 20% burn injury was inflicted. Control groups received gavage with 3H-B. fragilis or 3H-E. coli without burn. Four hours after burn or gavage was administered, the animals were killed, and the radionuclide and colony counts were determined in the mesenteric lymph nodes, liver, and spleen. Additional groups of mice receiving gavage (B. fragilis or E. coli) and burn were observed for 10 days to study survival. The results showed that 3H-B. fragilis translocated to a greater extent than 3H-E. coli but that fewer B. fragilis than E. coli survived in tissues. Survival was 86% for animals challenged with B. fragilis versus 53% for animals challenged with E. coli. It is concluded that in this model B. fragilis translocates extensively after burn injury and that survival is closely related to the destruction of translocated bacteria. PMID- 7775504 TI - A quasi-experimental, dual-center study of morphine efficacy in patients with burns. AB - The efficacy of morphine sulfate for the relief of pain and anxiety in patients with burns was investigated in a quasiexperimental, dual-center study. More than 100 patients at two burn centers in Iowa were studied. One of the units used no morphine or morphine derivatives for the control of pain (the no-morphine unit), and the other used moderate to high doses of morphine for the relief of pain (the morphine unit). Patients were asked to rate their pain and anxiety after hydrotherapy and at rest in the afternoon on a daily basis throughout their stays. Side effects were also measured, and nurses made ratings of the patients' pain and anxiety during morning hydrotherapy. Results indicated that pain and anxiety decreased significantly from hydrotherapy to afternoon assessments and decreased significantly during the patient's hospital stay. Unexpectedly, however, patients at the no-morphine unit consistently reported lower levels of pain and anxiety than did patients at the morphine unit. These results could not be explained by differences in burn size or number of surgeries across units. Other possible explanations are offered. PMID- 7775506 TI - Acute pseudo-obstruction in critically ill patients with burns. AB - Acute pseudo-obstruction of the colon (Ogilvie's syndrome) is a rare but potentially morbid complication of burn injury. Two thousand seven hundred three consecutive critically ill patients with burns were reviewed for findings consistent with pseudo-obstruction. Eight (0.29%) patients were identified. Mean age was 63.5 years, and mean burn size was 24.6% total body surface area. All patients were undergoing mechanical ventilation at the time of diagnosis. Six had a previous cardiac condition or complication, and five were on digoxin. Diagnosis was suspected in seven patients before colonoscopy or surgery. Six patients were treated with colonoscopy alone with one treatment failure. Two deaths occurred during hospitalization. Two late deaths were due to underlying cardiac conditions. The preferred treatment of Ogilvie's syndrome is nasogastric suction, colonic decompression, and close observation with surgery reserved for treatment failures or when diagnosis is in doubt. The incidence of Ogilvie's syndrome in patients with burns appears to be related to nonburn medical conditions, especially cardiopulmonary complications and age, rather than to the burn itself. PMID- 7775507 TI - A comparison of Xeroform and SkinTemp dressings in the healing of skin graft donor sites. AB - The best donor site dressing would minimize pain while it increased the rate of healing. This study compares a standard fine-mesh gauze dressing, Xeroform (Sherwood Medical Industries Ltd., Markham, Ontario, Canada), to a new collagen based dressing, SkinTemp (BioCore Inc., Topeka, Kan.). Eight patients requiring two donor sites of equal size received Xeroform gauze on one site and SkinTemp on the other. The Xeroform was covered for 24 hours and was then allowed to air-dry. Healing was determined to be complete once the gauze peeled off and complete epithelialization was observed. The SkinTemp was covered for 7 days and inspected on days 3, 5, and 7. Pain was measured daily with a standard visual analog scale. Mean Xeroform donor site size was 224.75 cm2, and SkinTemp size was 319.87 cm2. Donor site thickness was 0.012 to 0.014 inches for both. Mean length of healing was 10.62 days for Xeroform and 7.75 days for SkinTemp. Mean pain rating was 22.28 mm for Xeroform and 15.29 mm for SkinTemp. The overall preference of the eight subjects yielded five choosing SkinTemp and three choosing Xeroform, and seven reported SkinTemp as less painful. SkinTemp dressing appears to be less painful and has a better healing rate compared with Xeroform. PMID- 7775508 TI - An unusual mechanism of electrocution via a spray of aluminum paint. PMID- 7775509 TI - Clinical experience with the use of biodegradable tacks in pediatric patients with burns. AB - Stainless steel staples are very popular for securing grafts and dressings on patients with burns because of the speed and security with which they can be applied and the fact that stainless steel is nonreactive. In patients with large burns hundreds of staples are used and can be difficult to visualize and remove; they are therefore retained. Although stainless steel does not cause local tissue reaction, its presence can confuse the later evaluation of local pain. A new biodegradable tack has been developed. We describe an initial experience with this device in pediatric patients with burns and make suggestions regarding their use. PMID- 7775512 TI - Use of burn intensive care unit gymnasium as an adjunct to therapy. AB - One primary goal for patients with burns is to prevent loss in range of motion and function in the involved extremities. Because therapies were provided only on weekdays at our facility, the burn team designed a gymnasium that was built in the burn unit where patients can carry out their exercise programs after hours and on weekends. Patients assume responsibility to complete their occupational and physical therapy assignments, in addition to their other scheduled therapy sessions. The development of the burn intensive care unit gymnasium has increased the opportunity for patients to improve their range of motion and overall functional status. We have also noted that patients feel a greater sense of motivation and accomplishment when they are invited to take more control of their recovery. Assuming responsibility for their programs enables patients to achieve their goals, thus increasing their self-esteem after what is often a very devastating injury. PMID- 7775513 TI - Pain and anxiety during burn dressing changes: concordance between patients' and nurses' ratings and relation to medication administration and patient variables. AB - Few studies have examined the various factors related to pain during burn dressing changes. Patients' and nurses' ratings of pain and tension were obtained during 107 burn dressing changes among 11 burned patients. As found in previous studies, there was little concordance between nurses' and patients' ratings. Both nurses' and patients' ratings of pain were positively related to amount of analgesic medications administered, whereas amounts were inversely related to patients' reports of pain in a subsample of dressing changes in which anxiolytics were administered. However, these relationships failed to reach statistical significance. Multiple regression analyses revealed that ratings of tension during the procedure were significantly related to overall and worst pain, whereas amount of analgesics and anxiolytics given, postburn day, and total body surface area were not. Exploratory correlations suggested that ability to accurately discriminate between painful episodes, social desirability, and trait anxiety may be factors that significantly influence self-report of pain and might be worthwhile to study more systematically in the future. Implications for burn pain control and suggestions for future research are presented. PMID- 7775510 TI - Recent advances in absorbent products for the incontinent patient with burns. AB - The purpose of this study is to describe the physical configuration of disposable and reusable absorbent products and relate composition and construction to efficacy in the management of urinary incontinence in patients with burn injuries. The basic structure of a wearable absorbent product consists of three layers: a fluid-impermeable backing sheet, a fluid-pervious coverstock on the body-contacting surface, and an interposed absorbent core. The biomechanical performance of these absorbent products was determined by measuring the total absorbent capacity, defined as the maximum amount of liquid held by the product as a whole. On the basis of the results of this study, absorbent products are recommended for the incontinent patient with burns. PMID- 7775511 TI - A survey of the prevalence and application of chest physical therapy in U.S. burn centers. AB - The purpose of this study was to determine the prevalence and application of chest physical therapy (CPT) in burn centers. Respiratory therapists primarily administered CPT, and suctioning and coughing were the most frequently used modalities. Further study of the efficacy of treatment techniques is needed to develop congruous standards for CPT after a burn injury. PMID- 7775515 TI - School reintegration. AB - School reintegration programs have been developed to enhance a positive sense of self-worth in a child who has been burned. The premise of these programs is that cognitive and affective education about children with burns will diminish the anxiety of the patient with burns, the patient's family, faculty and staff of the school, and the students. Five principles guide school reentry programs: (1) preparation begins as soon as possible; (2) planning includes the patient and family; (3) each program is individualized; (4) each patient is encouraged to return to school quickly after hospital discharge; and (5) burn team professionals remain available for consultation to the school. Reintegration programs can vary in format depending on patient and/or family need and capability of the burn team, thus allowing flexibility in assisting every child with burns make the transition from hospital patient to normal living. PMID- 7775514 TI - Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids. AB - The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients. PMID- 7775516 TI - Recipe for postgraft antimicrobial wound cover. PMID- 7775517 TI - Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and fibroblasts for cultured skin grafts. AB - Cultured epidermal skin has become an adjunctive therapy for treatment of major burn injuries, but its effectiveness is greatly limited because of destruction by microbial contamination. To evaluate candidate antimicrobial agents for use with cultured skin, a combined cytotoxicity-antimicrobial assay system was developed for determination of toxicity to cultured human keratinocytes and fibroblasts and for determination of susceptibility or resistance of common burn wound organisms. Candidate agents including chlorhexidine gluconate, polymyxin B, mupirocin, sparfloxacin, or nitrofurazone were tested separately for inhibition of growth of human cells and for inhibitory activity to microorganisms with the wet disk assay. The data showed that (1) chlorhexidine gluconate (0.05%) was uniformly toxic to both cultured human cells and microorganisms; (2) nitrofurazone (0.02%) had dose-dependent toxicity to human cells and limited effectiveness against gram negative microorganisms; (3) sparfloxacin (30 micrograms/ml) had low toxicity to human cells and retained antimicrobial activity against both gram-positive and gram-negative bacteria; (4) polymyxin B (400 U/ml) was not toxic to human cells and had intermediate effectiveness on gram-negative bacteria; and (5) mupirocin (48 micrograms/ml) had no toxicity to skin cells and had uniform effectiveness against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus. Selection of topical antimicrobial drugs by these assays may improve effectiveness of cultured skin for burns and may be used to control other surgical wound infections. PMID- 7775518 TI - The changing image in cardiac surgery. PMID- 7775519 TI - Sternal wound infection: our experience with 200 cases. AB - More than 200 patients with sternal wound infections have been treated in the Plastic Surgery Department of our Medical Center over the years 1984-1993. Most of these were referrals from other hospitals. In recent years, the cases have become more severe, partially due to the fact that cardiac surgeons tend to operate older and sicker patients more readily than they previously did. 80% of these were post coronary bypass surgery, and the others heart and heart-lung transplants, repair of congenital heart anomalies, valve replacements etc. Several of the cases were cardiac surgery re-do's. Risk factors for developing this complication, such as diabetes, obesity, technical errors of sternal incision, prolonged intubation, the use of aortic balloon, etc. will be discussed. Many of our earlier patients had chronic fistulae following conservative therapy with old treatment modalities. In recent years, patients are usually referred at the acute stage. Most patients undergo removal of sternum and ribs. Previously, reconstruction included mainly transfer of the rectus ahdominis muscle, whereas lately the pectoralis muscles is utilized. Omentum was used in only one case. The importance of pre-operative imaging procedures has been thoroughly studied in our series. Especially important is the definition of the extent of the infection, and localization of foreign bodies causing chronic infections, such as suture material, epicardial electrodes etc. A change in infectants has also been noticed. In the first half of the study period, Pseudomonas aeruginosa comprised at least 40%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775520 TI - Stentless porcine bioprosthesis for aortic valve replacement. AB - We report herein our experience with the Toronto Stentless Porcine Valve (Toronto SPV, manufactured by St. Jude Medical Inc., Minneapolis, MN, USA) for aortic valve replacement (AVR). To date 146 SPV valves have been implanted, 29 in an initial clinical trial (from October 1987 to April 1987) and 117 in the current FDA trial (September 1991 to January 1994). In the current trial the majority of patients were male (76%), aortic stenosis was the dominant lesion (73%) and 68% of the patients received a valve size 27 mm or greater. The mean age was 61.3 +/- 12.0 years. For the entire group there has been no hospital death and no patient has required a pacemaker. Perioperative complications were myocardial infarction in three patients and suspect subacute bacterial endocarditis (medically treated) in three patients. There have been two late deaths (2%), two patients have had transient ischemic attacks (2%), and one patient suffered stroke with complete neurological recovery (1%). To date there has been no case of primary valve failure. Echocardiographic assessment of the SPV valve has demonstrated excellent effective valve orifice areas with very low transvalvular gradients and 95% of the patients had either 0 or 1+ insufficiency. These results are encouraging and justify the continued use of this valve in clinical trials. Further follow-up is required to determine its durability. PMID- 7775521 TI - Safety, feasibility and long term follow-up of a non-thoracotomy defibrillation system in patients with inducible sustained ventricular tachycardia/fibrillation. AB - A non-thoracotomy lead system CPI-ENDOTAK, a transvenous lead used alone or combined with a subcutaneous patch (SQ-P), was evaluated as an alternative to epicardial patches/electrodes in patients at high risk for sudden cardiac death undergoing implantable cardioverter-defibrillator (ICD) surgery. Fifty nine patients, 62 +/- 11.4 years with CAD (83.0%) cardiomyopathy (11.9%) other (5.1%), mean ejection fraction 31.8 +/- 14%, with inducible sustained VT/VF underwent testing of either lead alone or lead/SQ-P. Four configurations of NTL were tested. Fifty one patients had NTL implanted (lead alone = 60.8% and lead/SQ-P = 39.2%). Eight patients required non-NTL approaches, due to high DFT (7) or anatomic anomaly (1). DFT's were 19.1J (lead alone) and 20.8J (lead/SQ-P). Acute complications: pulmonary embolism 1, lead dislodgement 3, sensing malfunction 1. [table: see text] CONCLUSION: A NTL system using either a single transvenous lead alone or combined with SQ-P can be implanted successfully in high risk patients with a low incidence of acute complications. Non-arrhythmic survival is lowest in patients receiving defibrillation shocks. Arrhythmic survival is high in all patients. PMID- 7775522 TI - Mid-term results of heart transplantation in diabetic patients. AB - BACKGROUND: Diabetes mellitus (DM) has been considered a relative contraindication to heart transplantation (HTx) because of possible increased infection rates and worsening DM with prednisone immunosuppression. The introduction of cyclosporine has allowed us to reduce the dosage of oral steroids and to accept DM patients (pts) for HTx. We reviewed the mid-term outcome of our DM pts who had undergone HTx. MATERIALS AND METHODS: Out of 257 HTx recipients, 19 males and 3 females, aged 53 +/- 8 years, were diabetic. Prior to HTx, DM was controlled with insulin in 5, with oral hypoglycemic agents in 7 and with diet in the remaining patients. Immunosuppression consisted of cyclosporine and azathioprine; low-dose prednisone was added in 10 patients because of repeated rejections. RESULTS: All patients survived HTx and were followed 2 to 75 (mean 38 +/- 21) months. There were 4 late deaths, with actuarial survival of 84% at 5 years. DM was more difficult to control after HTx (12 patients requiring insulin vs 5 pre-HTx), but comparison of diabetic vs non diabetic patients following HTx showed no significant difference in frequency of rejection or infection during the 1st year (2.6 +/- 1.6 vs 2.1 +/- 1.5; 0.5 +/- 0.4 vs 0.4 +/- 0.3 episode/patient respectively) and in 5-year actuarial survival (84% vs 77%). Renal function is preserved in all DM patients, hypertension has developed in 11/18 (61%); annual post-HTx cardiac catheterisation has shown normal graft function and coronary arteries in all but 2 patients. CONCLUSIONS: Mid-term results indicate that HTx can be safely performed in diabetic patients; a longer follow-up is required to determine whether DM is no longer a contraindication to HTx. PMID- 7775523 TI - Warm continuous antegrade blood cardioplegia: applications in congenital heart disease. AB - Continuous warm blood cardioplegia is utilized by many surgeons as their method of choice for myocardial protection during operations for acquired heart disease. OBJECTIVE: this study was performed to determine the feasibility and safety of this method for intracardiac procedures through the right atrium and in particular, total cavopulmonary connection. MATERIALS AND METHODS: procedures included closure of an atrial septal defect (23), atrial septectomy (2) and total cavopulmonary connection (4). Antegrade blood cardioplegia was delivered continuously for an average of 27 +/- 21 minutes at an average flow of 130 +/- 60 cc/min to maintain the aortic root pressure between 60 and 80 mmHg (mean 74 +/- 5 mmHg). Perfusion with regular blood commenced in the last 2 to 8 minutes and complete de-airing procedure was performed on the beating heart before removal of the aortic cross-clamp. RESULTS: all patients resumed sinus rhythm and all but one had normal cardiac output postoperatively. In one patient after cavopulmonary connection the inferior vena-cava to pulmonary-artery connection was taken down because of increased pulmonary vascular resistance resulting in low output state. All patients made an uneventful recovery without neurological complications. CONCLUSIONS: this initial experience suggests that normothermic aerobic arrest can be used safely in the repair of congenital defects and may provide superior myocardial protection for complex procedures such as the Fontan procedure. PMID- 7775524 TI - Long-term results of plastic reconstructions in acquired aortic valvular disease. AB - Plastic surgery in acquired aortic valvular disease was performed in 164 patients. Among them, 9 had the isolated aortic valvular injury; 130 mitral aortic defects; and 25 three-valve injuries. The restoration of the injured valve function was achieved, as a rule, using a combination of surgical methods: commissurotomy or wedge resection of the fibrous tissue in the commissurial area; parietal resection; the aortic root frame plasty; perforation hole plasty; the allogenic valvuloaortic complex sector transplantation; and wedge resection or isometric cusp plication in the commissurial area. Calcinosis was not a contraindication to surgery, if it could be removed completely without the cusp closing function disturbances. The hospital mortality rate was 8%. After hospital treatment all the patients were followed-up: 108 for over 1 year, and the maximum term of the follow-up was 7 years. From 1 to 4 years postoperatively, 4 patients were reoperated due to the appearance of aortic insufficiency. The causes of relapse were: infectious endocarditis (3 patients); active rheumatic process (1 patient); and progressive dilatation of the fibrous ring (1 patient). During the follow-up 8 patients died: 6 of infectious endocarditis with mitral prosthetic injury; and in 2 the cause of death was not clear. The study of immediate and long-term aortic valvuloplasty results based on the clinical experience of 164 operations allows to recommend the elaborated principles of the aortic valve surgical reconstruction for a wide application in cardiac surgery. PMID- 7775525 TI - Management of hypoplastic aortic arch associated with neonatal coarctation. AB - Controversy still exists as to whether hypoplastic aortic arch frequently associated with neonatal coarctation, should be enlarged at the time of coarctation repair. To determine the indications for and the outcome of repair of hypoplastic aortic arch, pre- and postoperative angiograms/echocardigraphy of 77 cases with isolated (n = 25, Group 1) or complex (n = 52, Group 2) neonatal coarctation operated upon between 1/80 and 12/89 were reviewed. Age was 5-14 days (mean 8 +/- 1.6). Aortic arch/ascending aorta diameter ratio (AR/AA) as a measure of the degree of aortic arch hypoplasia was 0.39-0.64 (0.52 +/- 0.04) in isolated and 0.15-0.47 (0.34 +/- 0.06) in complex coarctation (p < 0.05). Left subclavian flap aortoplasty was used in 72 patients; alone in 25, in combination with pulmonary artery banding in 43 patients, and simultaneously with intracardiac repair in 4 patients. Extensive reconstruction of aortic arch and coarctation with synthetic patch was performed in the remaining 5 patients (AR/AO = 0.16 +/- 0.03) using cardiopulmonary by-pass at the time of intracardiac repair. Operative mortality was 2/76 (2.5%). Follow-up is 6.6 +/- 1.4 years. Recoarctation occurred in 3 patients (4%). AR/AA increased to 0.86 +/- 0.1 in isolated (p < 0.05 vs preoperative) and to 0.7 +/- 0.1 in complex coarctation (p < 0.05 vs preoperative). In the majority of cases, hypoplastic aortic arch associated with coarctation grows satisfactorily following simple repair of coarctation with no significant residual narrowing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775526 TI - Survival following resection of clinically occult N2 non small cell lung cancer. AB - BACKGROUND: The role of resection in Stage IIIA (N2) non-small cell lung cancer (NSCLC) remains controversial despite reported survival rates of 25-40%. This study was undertaken to identify factors associated with a high risk of treatment failure after resection of clinically occult Stage IIIA (N2) NSCLC: Such prognostic factors may identify high risk patients as candidates for future clinical trials of multimodality lung cancer treatment and be important stratification factors in such trials. METHODS: The clinical and pathological records of 32 patients with clinical NO pathologic N2 NSCLC who underwent lobectomy (n = 17), pneumonectomy (n = 12), or bilobectomy (n = 3) and complete mediastinal lymph node dissection at Fox Chase Cancer Center from 1987 to 1991 were reviewed. A multivariate analysis of clinical and pathologic variables was performed. RESULTS: Median follow-up was 15 months (range 5-55). Fifty-nine percent have recurred and 44% have died. Median disease free and overall survival were 16 and 19 months, respectively. Two year disease free and overall survival were 24% and 43%, respectively. No patient with more than one level of mediastinal lymph node metastases survived two years free of disease. Univariate and multivariate analysis revealed a longer disease free survival for those receiving adjuvant radiation therapy (19 vs 5 months) but no increase in overall survival. CONCLUSIONS: This experience with clinically occult Stage IIIA (N2) NSCLC suggests that multiple levels of mediastinal lymph node metastases predict treatment failure in patients following resection and that adjuvant mediastinal radiation improves disease free but not overall survival. PMID- 7775527 TI - Surgery in the management of mediastinal carcinoid. AB - Primary carcinoid tumors of the mediastinum were described for the first time in 1972 as thymic carcinoids. Our experience with 16 patients who underwent diagnostic and surgical procedures at the Mayo Clinic is presented. All of these patients had mediastinal carcinoid. The surgical procedures included node biopsy, anterior mediastinotomy (Chamberlain), median sternotomy and posterior lateral thoracotomy. Complete resection was possible in 9 (56.3%) patients, 3 (18.7%) had partial removal (debulking), and 4 (25%) had diagnostic biopsies only. The operative morbidity was 25%. There were no postoperative deaths. In resectable patients, the average disease free interval was 45.7 months. Five year and ten year survival was 47% and 22%, respectively. Local or distant metastatic spread developed in all patients (100%). Mediastinal carcinoids are a separate entity from other thymic and mediastinal neoplasms. (We suggest that) Surgical excision may be possible earlier in the disease and radiation and chemotherapy are of doubtful value. PMID- 7775528 TI - Balancing the circulation in hypoplastic left heart syndrome. AB - A mathematical model based on oxygen flow was developed to study the effects of pulmonary to systemic flow ratios (QP/QS) on systemic oxygen availability. The model suggests that QP/QS = 1 is the safest ratio that would provide the largest safety margin in either low cardiac output or low pulmonary oxygenation conditions. The optimal value of QP/QS that will result in maximum oxygen availability is smaller than unity and depends on several circulatory parameters such as cardiac output, maximal oxygen capacity, level of pulmonary oxygenation, and oxygen consumption. The values of these parameters also dictate the permissible range of QP/QS beyond which abrupt oxygen deficiency ensues. Decreased pulmonary resistance resulting in increased pulmonary flow may eventually result in QP/QS that is beyond the vital range. PMID- 7775529 TI - Follow-up of infants after systemic-pulmonary shunts, performed with fresh frozen vein homografts. Postoperative angiographic assessment. AB - Ten of twenty-six modified Blalock-Taussig shunts performed with fresh frozen vein homograft were studied angiographically. In two of them the shunt was stenosed. The remaining eight shunts were satisfactory. Among them in four irregularities of the inner surface and in four spindle shape of the shunt were observed. The diameter ratio between subclavian artery and homograft at the time of operation and later as seen on the angiograms did not change. This suggests that spindle shape of homograft is caused by growth rather than by aneurysm formation. PMID- 7775530 TI - Some questions about Eurocollins solution used for lung preservation. AB - Currently, Eurocollins' (EC) solution (high-potassium concentration) is the most widely clinically used pulmonary perfusate. However, recently, experimental studies have reported an increase of the lung ischemic period using low-potassium solutions. The purpose of our study, is to investigate the influence of the EC ionic composition and the effect of hyperosmolarity due to the glucose concentration on isolated alveolar type II epithelial cells. Pneumocytes type II were isolated from pathogen free Wistar rats using the modified Dobbs' method. Cells were incubated for 6 hours at 4 degrees C in EC, Collins (CL) and Ringer Lactate (RL) solutions. After that, cellular viability was evaluated by analysis of the protein synthesis assay by measuring the 35 S methionine uptake during an incorporation period of one hour at 37 degrees C (picomol 35 S met/mg proteins/h). Mean +/- standard deviation and Student "t"-test were used for data presentation and results comparison. Cellular viability at time 0 (control) before cellular incubation was 3.93 +/- 0.38. After 6 hours at 4 degrees C the results were respectively as follows: EC = 2.16 +/- 0.13; CL = 2.63 +/- 0; RL = 3.21 +/- 0.04. Our results suggest that the low-potassium extracellular type solution (RL) shows a protection on isolated type II epithelial cells statistically significant (p < 0.05) if compared with EC solution. Moreover CL solution, that has the same ionic composition EC but without glucose, presents a less cytotoxic effects on incubated cells than EC, confirming a deleterious influence of solution hyperosmolarity. PMID- 7775531 TI - Cardiomyoplasty review: physiological principles and characteristics of electrically stimulated skeletal muscle. II. A therapeutic option. AB - Chronic heart failure continues unsolved as ever despite recent advances in cardiac surgery and pharmacological new armamentarium and remains a significant cause of death, regardless of etiology. Cardiomyoplasty (CMP), a new form of biomechanical ventricular support, has given new life to the field of mechanical circulatory support, providing a "bridge" to transplantation and serving as a possible alternative to surgical treatment. The geographic distribution of world experience in 401 patients shows that 80% were centralized in Europe (50%) and South America (30%). This review of the data analysis, documented improved changes in patients clinical status, further clarifies and appropriate patients population indications for DCMP as well as that more than 80% survival probability for NYHA class II & III and an early procedure related mortality of 8 to 10%. PMID- 7775532 TI - Chronic post thoracotomy pain. AB - Chronic post-thoracotomy pain (CPP) is a vexing clinical problem whose management has received scant attention. In order to identify the risk factors associated with CPP and determine the optimal treatment, the records of 238 consecutive patients who underwent thoracotomy were reviewed. CPP was defined as discomfort requiring the regular administration of analgesics that continued more than three months following surgery. CPP was present in 25 (11%) patients: 10/20 (50%) chest wall resections, 5/25 (20%) pleurectomies, 10/193 (5%) pulmonary resections. Among the 23 patients who required preoperative narcotics, 12 (52%) developed CPP. Improved pain control and decreased narcotic use was achieved via the administration of nonsteroidal anti-inflammatory medication and tricyclic anti depressants. In addition, 10/25 patients required 11 pain procedures: trigger point injection, intercostal blocks, injections of epidural steroids, stellate ganglion block. Recurrent pain occurred in 20 patients following initial control. All were found to have tumor regrowth. We conclude that CPP occurs more commonly following chest-wall resection and pleurectomy, and that preoperative narcotic use is a predictor of CPP. Worsening pain following initial relief should prompt a vigorous search for recurrent cancer. PMID- 7775535 TI - The role of pleuroscopy in the management of resistant empyema. PMID- 7775533 TI - The first step of experimental study on hybrid trachea: use of cultured fibroblasts with artificial matrix. AB - Anastomotic stenosis secondary to developing granulation tissue prevents an artificial trachea of non-porous type model from a safe practical use. Taira reported that a non-porous artificial trachea having soft ends for anastomosis works better in this regards apparently by cushioning mechanical stimulations repeatedly applied to the anastomotic rings than most models ever studied have done. We hypothesized that hybridization of soft anastomotic ends of nonporous artificial trachea may further prevent granulation tissue at the anastomoses hopefully by leading epithelial growth earlier onto the inner surface of graft's ends. The graft of our use was made of a 5-cm-long knitted dacron tube with inner coating with silicone rubber covering the entire length but for a 5 mm segment at each end. To date six mongrel dogs have been subjected to test this hypothesis. A piece of subcutaneous tissue was obtained from each dog and prepared for culture of fibroblasts in MEM. These fibroblasts were then suspended in 0.1% collagen with MEM in a container, in which a graft was placed for further culture. Following some 3 weeks of this preparation each graft was implanted to replace a 10-cartilage-ring-long defect of the mediastinal trachea of each donor dog. One dog is enjoying active life 11 months postop, and another 3 months. Four dogs died from anastomotic stenosis 2 to 3 months. Being encouraged by the fact that the anastomotic rings of the long term survivors show bronchoscopically patency more than 40% of cut surface area, and some portion with possible epithelialization without granulation, we will report our further results, along with histological study. PMID- 7775534 TI - Video assisted thoracic surgery: our experience with 102 patients. AB - Recent advances in optics, video systems and endoscopic operating instruments have made thoracoscopy easier and more accurate. From May 1992 until December 1993 we performed 102 Video Assisted Thoracic Surgical Procedure (VATS) for diagnosis and treatment. Twenty patients underwent thoracoscopy, twelve had pleurodesis. Seventy operative thoracoscopies included pulmonary wedge resection, dorsal sympathectomy, management of empyema, pleural tumor, bullectomy, pericardial window, anterior release for kyphoscoliosis and resection of posterior mediastinal cyst. In most cases of parenchyma resection, it was necessary to use three ports: one for video-endoscopy and two for preparation instruments and stapler. The average operation time was 58 minutes and average hospital stay was 3.5 days. Four patients died within 30 days after the procedure due to multi-organ failure, end-stage malignant disease and post pneumonectomy pulmonary edema, unrelated to the VATS itself. One patient had thoracotomy due to uncontrolled bleeding. No wound infection or other postoperative complication except intercostal neuralgia after dorsal sympathectomy was noticed. Localization of the target lesion deep within the parenchyma of the lung still poses a problem. We used a small incision (2 cm long), placing a finger to directly palpate the lung and locate the lesion, or made a mini thoracotomy. Conversion to thoracotomy was performed when malignancy was demonstrated at frozen section. CONCLUSIONS: 1) Thoracoscopy is a minimally invasive surgical technique causing a low morbidity rate and attaining a high diagnostic accuracy. 2) Postoperative recovery is brief and uneventful. New techniques of imaging are needed to locate the target lesion. PMID- 7775536 TI - Intermittent antegrade cardioplegia: warm blood vs cold crystalloid. A clinical study. AB - Intermittent antegrade warm blood cardioplegia (IAWBC) is a not usual technique of myocardial protection. We propose a delivery protocol that standardizes the length of ischemic intervals, duration of each cardioplegic dose and K+ amount. Cardioplegia is represented by blood, taken from the oxygenator and injected directly into the aortic root, and K+, added by means of a syringe pump. We reviewed the first 300 patients who underwent elective or urgent coronary artery by-pass procedures (group A) and compared them with the last 300 patients operated on with intermittent antegrade cold crystalloid cardioplegia (group B). The overall mortality in group A was lower than in group B (0.7 vs 3.0, p < 0.05); there was no in-hospital death in patients with poor left ventricle (LVEF < 35%) in group A (0/64 vs 3/39, p < 0.025). Reduction of mortality was due to a drastic fall of morbidity. In group A no patients needed circulatory assistance (13 in group B, p < 0.0005) or intraaortic balloon pumping (9 in group B, p < 0.005) in operating room or in intensive care unit (ICU); only 1 patient had inotropic drug (29 in group B, p < 0.0005) and only 6 needed lignocaine infusion (27 in group B, p < 0.0005). Incidence of postoperative myocardial infarction was lower in group A (4 vs 9 in group B) as well cerebrovascular accidents (4 vs 10 in group B), but difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775537 TI - The mitral valve replacement by the new-type bioprostheses (features of design and long-term results). AB - The BAKS bioprostheses were created in our centre and they have the following features: (1) to reduce immunogenicity they underwent a combined fermentochemical treatment which resulted in the native xenovalve consisting of collagen and elastic fibres only; (2) in cutting out the valve the natural aortic sinuses were preserved; and (3) the xenovalve was fixed on a functional frame of an original design. From 1979, BAKS have been implanted in 243 patients with the isolated mitral valve reumatic injury. The patients age varied from 11 to 59 years; 91 patients (37.5%) were under 35 years. The 12-year survival rate (without hospital lethality) was 65.5 +/- 5.3%. The most serious longterm complications were: infectious endocarditis (3.14 patients/years); spontaneous degeneration of bioprosthetic cusps (2.24% patients/years); thromboembolism (0.6% patients/years). The morphological examination of bioprostheses removed in reoperations from 10 days to 10 years after implantation was performed in 51 cases. Most often, collagen degeneration occurred in patients under 35. The pathologic structural changes originated because of the localized saturation of bioprosthetic cusps with the recipient plasma proteins, gradual disintegration of collagen fibres, and further calcification of that area. The indications to the mitral valve replacement by BAKS were: the left atrium thrombosis, thromboembolytic syndrome, contraindications to anticoagulation therapy, and the age over 35 years. PMID- 7775538 TI - T-graft: a new method of coronary arterial revascularization. AB - We present early results in 486 patients undergoing total coronary artery revascularization using a T-graft constructed from the attached left internal thoracic artery (LITA) and the free right internal thoracic artery (RITA). The anterior and anterolateral areas of the heart are by-passed with the LITA and the inferolateral, inferior and posterior areas are by-passed with the RITA. These patients received an average of 4.34 distal anastomoses with as many as four from each of the limbs of the T-graft. Ages ranged from 29 to 89 years and ejection fractions from 15 to 79%. Sixty-six patients were undergoing first reoperations and 6 received T-grafts at their second reoperation. The mortality at 30 days was 2.3%. Two of 92 women and 9 of 394 men expired. The perioperative infarction rate was 1.2%. Postoperative angiography in 34 patients showed 98.3% of LITA and 86.5% of RITA anastomoses to be patent. There was a slightly higher patency observed in women. The T-graft technique can be applied to nearly all patients with 3 vessel coronary artery disease with low operative mortality. Precise technique with high power magnification is crucial. This procedure has the potential of avoiding further invasive procedures due to graft deterioration in many patients with 3 vessel coronary artery disease. PMID- 7775539 TI - Results of mitral valve reconstruction in mitral valve insufficiency. AB - In the last three years forty mitral valve reconstruction (MR) procedures were performed in case of mitral insufficiency (MI). In three cases, anatomical changes made reconstruction impossible for us. One patient had to be re-operated because of unsatisfactory valve function. There was no operative mortality. In twelve of the patients, mitral insufficiency was the only problem, while in twenty eight others additional cardiac procedures (CABG, AVR) were performed. The patients' age ranged from 17 to 77 years. The aortic cross-clamping time for mitral reconstruction without additional cardiac procedures ranged from 35 to 134 minutes. With one exception, the post-operative TEE indicated no, or very little, insufficiency. We concluded that the mitral valve insufficiency can be corrected with very good results and with a very low rate of complications. Such corrections ought therefore be taken into consideration before valve replacement. PMID- 7775540 TI - Single centre experience with the Jyros bileaflet rotating pyrolitic carbon valve. PMID- 7775541 TI - Sorin Bicarbon heart valve: early experience. PMID- 7775542 TI - Cardiac surgery in octogenarians. AB - Age as an important risk factor in surgery has always been debatable. Between January 1991 and December 1992, 35 consecutive octogenarian patients (23 males and 12 females; average age 82.3 years) were retrospectively evaluated. Twenty five patients had only coronary artery by-pass graft operations (CABG), five had aortic valve replacements (AVR) and five had combined AVR-CABG operations. Twenty five of the 30 patients (83%) who underwent CABG alone or a combined procedure had suffered from unstable angina. The mean ejection fraction was 40% in this group. An average of 2.8 grafts per patient was performed. The left internal mammary artery (LIMA) was-used in nine patients (30%). The average hospitalization period was 11.5 days. Operative mortality (within 30 days) was zero. Patients who underwent AVR only were hospitalized for an average of 17.6 days and there were two cases (6%) of mortality in this group. All patients who underwent AVR and CABG were discharged within 14 days. Overall complications occurred in nine patients (25.7%); cardiac arrythmias, (4) neurological deficits (2), severe wound infections (2), and adult respiratory distress syndrome (1). The use of the LIMA was not associated with an increased incidence of bleeding or sternal infection. The low rates of mortality and major complications lead us to conclude that, when indicated, surgical treatment including the use of LIMA in selected cases, should be offered to this group of patients, even in the presence of moderate LV dysfunction. PMID- 7775544 TI - The management of soft tissue complications related to pacemaker implantations. AB - During the last six years (1988-1993) we have treated 15 patients suffering from soft tissue problems related to pacemaker implantations which included: skin erosions (2 patients), impending extrusion of the pacemaker pulse generator due to capsular contracture (4 patients), exposed pacemaker generator (6 patients), and exposed electrode (3 patients). This article describes a conservative approach to the treatment of these complications. Skin erosions are treated topically with antibacterial creams or solutions. Local infection is controlled by the administration of systemic antibiotics according to the antibiogram, as well as with local antibacterial dressings. Impending extrusion or exposure of the pacing system are treated by subcapsular relocation of the pacemaker generator or vertical-to-horizontal transposition of the exteriorized lead. These restricted local surgical interventions are designed to overcome the vertical force which tends to cause the extrusion of pacing hardware without using another implantation site which are already limited in number. This approach, which can be repeated, prevents the reintroduction of a new pacing system. The pre operative evaluation, surgical techniques and a long term follow-up are presented. PMID- 7775543 TI - Transvenous implantable cardiovascular defibrillator lead system: experience in 28 patients. AB - Morbidity and mortality following Automatic Implantable Cardioverter Defibrillation (AICD) is mostly related to thoracotomy performed during placement of epicardial leads. From July 1991 to January 1994, a transvenous lead system (TLS) (Endotak C; CPI) was implanted in 28 patients (24 males, 4 females, age 15 76 years) who suffered from life threatening ventricular tachyarrhythmias. Twenty four patients had a previous MI, mean LVEF was 26% (14-65%), two had mitral valve prolapse (one with prolonged QT), one had hypertrophic and another had dilated cardiomyopathy. The implantation procedure was performed in the operating room (n = 26) or in the Cath lab. (n = 2). Nineteen (out of the 28) patients were treated with Amiodarome before implantation (5 out of 7 had LVEF < 30%). A satisfactory defibrillation threshold (DFT) was achieved using Endotak lead alone in 22 (79%) patients. These patients had LVEF between 10% to 65% (less than 30% in three patients). In six patients the DFT was measured as lower than 20 J, and a subcutaneous patch was added (LVEF 12-38%, 4 patients with Amiodarome therapy). The implanted devices were all from CPI: 1600 (n = 5), PRX (n = 7), P2 (n = 15), PRX II (n = 1). During a 1-32 months of follow-up one patient died from severe CHF. The implanted device operated in 9/28 patients. The only complication related to implantation was infection at the pocket site (n = 2), which responded to antibiotic therapy in one patient, but required device explantation in another patient. The device was reimplanted in that patient three month later, with no further complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775545 TI - Ruptured aneurysm of the sinus of Valsalva. Clinical review, treatment results. AB - Five patients were operated on because of ruptured aneurysm of the sinus of Valsalva. In the cases with no concomitant VSD the surgical access from the aorta was used. The aorta was opened and the Fogarty catheter was introduced to the fistula. The "wind sock" of the aneurysm was pulled back to the aorta and excised. The opening was closed with double-line pledgetted polypropylene sutures. In severe aortic incompetence mechanical prostheses were implanted. One patient had bacterial endocarditis with reopening of the fistula and aortic valve incompetence that required reoperation. All patients are in a good clinical state. We recommend the use of Dacron patches even in small aneurysms to avoid re opening of the fistula. PMID- 7775546 TI - Cryopreservation of veins as an alternative to autografts in coronary by-pass grafting. AB - Cryopreserved venous segments could be used as allografts in coronary by-pass surgery in patients with limited availability of venous or arterial conduits for autologous grafting. After primarily disappointing clinical results it was the aim of these experiments to improve freezing procedure and incubation media in order to maintain most of the functional integrity of the biological material after cryopreservation, and thus to contribute to the essential prerequisites for a successful implantation. Freshly prepared segments of human saphenous vein were cryopreserved: 1) using various computer-assisted freezing programs with definite cooling rates and seeding temperatures; 2) after incubation in media consisting of RPMI 1640 and cryoprotective agents in different combinations and concentrations. The veins were stored at -196 degrees C, thawed quickly and analyzed in an in vitro perfusion system. The degree of vitality of the vein segments was assessed by measuring vasoconstriction after application of Norepinephrine and Serotonine and vasodilatation following release of endothelium derived relaxing factor (EDRF) after perfusion with Acetylcholine. Our results show that the preservation of vascular smooth muscle can be maintained only by: 1) equilibrating the vein in RPMI 1640 with 2.2 M Glycerol and 1.6 M Ethylene Glycol and 2) preventing an increase of temperature during the crystallization in the cooling process. The results clearly demonstrate the maintainance of vitality in vein segments after an appropriate freezing and equilibration process with specific cryoprotective agents. The data obtained in the study could serve as the basis for a better longterm prognosis of transplanted cryopreserved venous allografts. PMID- 7775547 TI - Coronary artery by-pass without cardiopulmonary by-pass for patients with severe left ventricular dysfunction. AB - OBJECTIVES: To evaluate results of coronary artery bypass grafting (CABG) without cardiopulmonary by-pass (CPB) for patients with severe left ventricular dysfunction. MATERIALS AND METHODS: Fifty-three patients with severe LV dysfunction (EF < 35%) underwent CABG without cardiopulmonary by-pass (CPB) between December 1991 and December 1993. They comprise 22% of 242 patients operated on without CPB by one of the authors (RM) in this period. There were 45 (85%) males and eight (15%) females. Twelve (23%) patients were over 70 years. Nine (17%) were re-do CABG. Ten (19%) were referred for operation within the first 24 hours of evolving MI, and 13 (25%) up to two weeks after acute MI. Nine (17%) had preoperative EF < 20%, and six patients (11%) were in cardiogenic shock. Mean number of grafts/pt was 1.8 and IMA was used in 41 (77%). Only 14 patients (26%) received a graft to a circumflex marginal artery. Ischemic time was 8 +/- 4 min/graft (mean +/- SD) when anastomosed to the LAD or RCA, and 14 +/ 7 min/graft when anastomosed to a marginal branch. RESULTS: One patient (1.9%) died perioperatively, and two (3.7%) suffered a non-fatal MI. At two-year follow up there were three late deaths, one of them from cancer. Three patients had return of angina, two of them were reoperated upon. CONCLUSIONS: These results suggest that CABG without CPB may be advantageous for patients with severe LV dysfunction. PMID- 7775548 TI - Perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary by-pass surgery. AB - A randomised study was performed on 70 patients undergoing elective coronary by pass procedure to examine whether the combined, perioperative, 24-hour infusion of nifedipine and metoprolol reduces the incidence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine only. Repeated assessments of serum enzyme levels and 12-lead-ECG together with a 3-channel Holter monitoring over 48h were used to classify perioperative myocardial ischemia and supraventricular and ventricular arrhythmias. The two groups did not differ with respect to their demographic data, extracorporeal circulation, aortic cross-clamping time, or number of distal anastomosis. No perioperative myocardial infarction in either group was detected. However, a significantly lower incidence of transient ischemic event was observed in the NM group as compared transient ischemic events was observed in the NM group as compared to the N group. In addition, there was a tendency towards lower CK-MB-level and peak-values of CK- and CK-MB-enzymes in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the NM group as compared to the N group. In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine. PMID- 7775549 TI - Total preservation of chordae tendinae in mitral valve replacement (MVR). AB - Chordal papillary integrity is crucial for a good left ventricular performance following mitral valve surgery. From June 1991-July 1993 (2 years), 200 mitral surgeries were performed by the authors out of which MVR were done by preserving all chordae tendineae in 36 patients (18%), ages 11-64 years (mean 36 +/- 13.2 SD), female to male ratio 3:1, New York Heart Association (NYHA) functional class III-IV. Preoperative workup revealed pure mitral stenosis (MS) in 12 patients (33%), mitral regurgitation (MR) in 16 (44%), MS + MR in 7 (19%), MS + aortic regurgitation (AR) in 4 (11%), MR + secundum atrial septal defect (ASD) in 2 (6%), MR + primum ASD in 1, MR + coronary artery disease (CAD) in 1 (3%) and moderate to severe pulmonary hypertension in all. Twenty-two patients (61%) had MVR only, 4 (11%) had MVR + aortic valve replacement (AVR), 10 (29%) had MVR + tricuspid annuloplasty (TVA), MVR + secundum ASD closure in 2 (6%), MVR+primum ASD closure in 1 (3%) and MVR + coronary artery bypass grafting (CABG) in 1 (3%). Bioprosthesis used were: St. Vincents 17 (47%) and Carpentier Edwards 2 (6%). Mechanical valves used were: St. Jude's 1 (3%), Bjork-Shiley 2 (6%), St. Vincents 5 (14%), CarboMedics 9 (25%). Success of the procedure were accomplished in all (100%) and was judged by extubation period of 6-18 hours, decreased pulmonary artery pressure, good prosthetic function and adequate ventricular performance by subsequent echocardiographic assessments. There were no early (< 30 days) mortality. All patients showed NYHA functional class I-II except in one with Marfan syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775550 TI - Thoraco-abdominal aneurysm resection. Determinants of survival in a community hospital. AB - Twenty-five patients who underwent resection of a thoraco-abdominal aneurysm between 1985-1993 were reviewed to study determinants of survival in patients undergoing the procedure in a community hospital. Twelve procedures were performed electively, six urgently and seven emergently. Type I aneurysm was present in one patient (n = 1), Type II n = 7; Type III n = 5 and Type IV = 12. Hypertension (n = 17), cardiac disease (n = 10) and renal insufficiency (n = 4) were most common risk factors. Aneurysms were repaired using inclusion method without special techniques for renal or spinal cord preservation. Eighteen patients survived and were discharged; four patients died 30 days and three patients died 30 days. Causes of death were multisystem failure (n = 3), acute myocardial infarction (n = 2) coagulopathy (n = 1) and bowel infarction (n = 1). Major complications included renal failure (n = 2) myocardial infarction (n = 3), bleeding (n = 3), paraplegia (n = 1). Statistical significance was determined using Fisher's exact test-2 tail. Risk factors for death and complication included emergency or urgent surgery (4 deaths-emergent, 2 deaths-urgent) and preoperative renal insufficiency (2 deaths; 1 dialysis) 52% of patients in a community hospital setting underwent emergent or urgent operation and this accounted for 87% of deaths and most morbidity. Mortality in elective procedures was 8%. Based on this data, we believe that thoracoabdominal aneurysm resection can be reasonably undertaken in a community-type hospital. PMID- 7775551 TI - A half century of cardiovascular surgery: reflections. PMID- 7775552 TI - Porcine stentless aortic heart valve substitute mid-term clinical follow-up. AB - From May 1990 to January 1994, 120 patients underwent aortic valve replacement with the use of the Biocor porcine aortic stentless heart valve (BPASHV). There were 83 male and 3 female patients. The age ranged from 11 seventy-six (76) years with a mean of 36. Eighty-five patients were under 40 years of age. Sixty-four patients underwent their first aortic valve replacement due to rheumatic heart disease, 30 because of prosthetic valve failure and of those: 20 were due to primary tissue failure and in 10 due to prosthetic endocarditis, native aortic bicuspid valve in 11 and senile calcificant aortic valve disease in four. Thirty three patients had aortic annular related pathology. Their preoperative functional class revealed 61 patients in class III and 59 in class IV. The longest follow-up in this aortic group was 42 months with a mean of 26. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of six patients (5%). The mortality was not valve related. The hospital morbidity in 14 revealed full recovery of all patients. There were four late reoperations, in two due to recurrent endocarditis and in the last two because of paravalvar leak. There was a late mortality of four patients (non valve related). The follow-up of these patients revealed full competent aortic stentless valve in 97 patients and only minor jet in nine. Most patients are in functional class I and II. The Aortic stentless concept has proven to be outstanding with the use of the Biocor Aortic stentless valve throughout the current follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775553 TI - Allograft aortic valve replacement. A comparison of the free-hand technique versus aortic root replacement. AB - OBJECTIVE: Comparing the results of aortic valve replacement (AVR) with cryopreserved allografts using two operative techniques: the free-hand and aortic root replacement. DESIGN AND SETTING: A cohort study in a tertiary care center. PATIENTS: Fifty eight patients underwent allograft AVR during the years 1987 1994. The free-hand technique was used in 40 patients (group A) and aortic root replacement in 18 (group B). OUTCOME MEASURES: Perioperative morbidity, mortality, blood transfusion requirement and length of hospital stay. Mid-term survival, functional class and valve related complications. RESULTS: Early mortality-2 patients (11%) in group B, none in group A (p = 0.09). Patients in group B received more donor exposure from blood products than group A (28.4 +/- 29.8 donors versus 3.8 +/- 6.1 donors, p < 0.00001). Perioperative complications occurred more often in group B (p = 0.042). However, the length of hospital stay was similar. Long-term follow-up ranged from 1 to 73 months (median 43 months). There was one non-valve related late death. No recurrence of endocarditis, or thromboembolic events were observed. 96% of the patients were in NYHA class I or II. Of these, echocardiogram showed trace or no aortic regurgitation (AR) in 96%. In group A one allograft was rereplaced with a mechanical valve for a technical failure, and mild and moderate AR were documented in two patients. This was not significantly different from group B. CONCLUSIONS: Aortic allograft durability at 6 years is excellent and the overall valve-related complication rate is extremely low. The differences between the two groups were too small to demonstrate a clear cut superiority to any of the techniques. However, our results suggest that aortic root replacement is associated with increased early morbidity and mortality when used for more complex aortic valve and aortic root pathology, whereas the free-hand technique may be associated with more mid-term valvular insufficiency. PMID- 7775554 TI - Porcine stentless mitral heart valve substitute: short term clinical data. AB - Beginning March 1992 to February 1994, 65 patients were submitted to mitral valve replacement using the porcine mitral stentless heart valve. This group took in 65 patients, their age ranged from four to 65 with a mean of 26 years. Forty patients were below years of age. The major indication was rheumatic heart disease sequelae in 50 patients, mitral valve endocarditis in six, myomatous degeneration in four and in five previous mitral prosthetic valve was replaced due to tissue failure. The preoperative functional class revealed 35 patients in class III and 30 in class IV. The longest follow-up was 23 months with a mean of 12. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of two patients or 3.1%. The hospital morbidity revealed full recovery of all patients. There were three patients reoperated because of valve endocarditis in two and in one due to partial dehiscence of the suture at the annular level. All three patients had full recovery after a reoperation. There was a late mortality of two patients, non valve related. The follow-up of these patients revealed full competent stentless mitral valve in 50 patients and in nine minor to mild jets were encountered by color echo-Doppler. Most patients are in functional class I and II. The stenless concept has prove to be outstanding in the mitral position throughout the current follow-up of close to 2 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775555 TI - Optimal approach for mitral valve surgery. AB - It seems that mitral valve (MV) replacement technique is already standardized but still under discussion is the surgical approach. At Heart Surgery Clinic of Vilnius University MV replacement was started in 1970 (our total experience in valve surgery is 4396 operations). The most popular surgical approach was through left atrium (LA) from the right side. In cases with small atrium we used right atrial and transseptal and transverse transeptal biatrial (TTBA) approach. Left atrium approach is quite useful in many cases except those with small LA, LV hypertrophy and heart rotation when it can result a greater trauma for the heart, extended time of operation and, possibly, reduced performance after it. From September 1992 till May 1993 we used extended vertical transseptal (EVT) approach in 18 patients for MV replacement or repair, mitral and aortic valve replacement was performed for 5 patients, mitral valve replacement and tricuspid valvuloplasty for 13 patients, 5 patients had mitral valve reoperations and for 3 patients aortocoronary by-pass performed additionally. The technique used was exactly as proposed by O. Alfieri et al, and incorporated bicaval cannulation and vertical transseptal incision extended into the roof of LA. From the first operation it became clear that this approach was superior to all others we had used during 20 years, since it gives perfect visibility of mitral valve, does not require retractors (only traction sutures are applied) and allows even to very easily use the continuous suture for valve fixation. Size of LA is no longer important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775556 TI - Early multicentre experience with the Jyros Bileaflet solid pyrolitic carbon rotating valve. PMID- 7775557 TI - Mechanical assistance as a bridge to transplantation different indications for different devices. PMID- 7775558 TI - Coronary by-pass reoperations without cardiopulmonary by-pass: the Israeli experience. AB - OBJECTIVES: To evaluate results of coronary artery by-pass grafting (CABG) reoperations without cardiopulmonary by-pass (CPB). MATERIALS AND METHODS: Thirty two patients underwent CABG reoperation with CPB between December 1991 and December 1993. There were 29 (91%) males, and 3 (9%) females. Mean age was 62 +/- 7 years. Five (16%) were operated on emergently, two (6%) of them during cardiogenic shock. Three (9%) were referred for operation up to two weeks following acute MI. Six (19%) had preoperative EF < 35%. Significant associated systemic diseases included previous CVA in two patients (6%), calcified aorta in two (6%), peripheral vascular disease in six (19%), renal failure in one (3%), and severe COPD in one (3%). Mean number of grafts/pt was 1.5 (range 1-3), and IMA was used in 26 (81%) of patients. Only nine patients (28%) received a graft to a circumflex marginal artery, six (66%) of whom were operated on through left thoracotomy. RESULTS: Only two patients (6%) had low output syndrome postoperatively; one was supported with catecholamines, and the other with intraaortic balloon pump. Hospital stay was 6.1 +/- 1.5 days (mean +/- SD). Early unfavorable outcome included operative death in one patient (3.1%), non-fatal MI in two (6%), and sternal infection in one (3%). Follow-up (10 +/- 5 months, mean +/- SD) showed two late deaths (one cardiac, and one carcinoma), one (3%) non fatal MI, and return of angina in three (9%) patients. CONCLUSIONS: CABG reoperations without CPB should be considered, particularly for revascularization of the LAD and RCA systems. Left thoracotomy is optional for patients with disease confined to circumflex and LAD systems. PMID- 7775559 TI - Therapy and results of surgery: requiring infarction complications. An 8-year experience. AB - Among myocardial infarction (MI) secondary complications requiring surgical intervention, the primary sequel is the left ventricular aneurysm (LVA), as a matter of fact, the ventricle septum rupture (VSR) and the moderate to severe ischemic mitral valve regurgitation (IMR) are common as secondary or third follow ones. Between June 1985 and June 1993 in our department, we performed 6418 operations with the support of the heart-lung-machine. This number includes 74 (1.15%) operations of MI complications; 38 interventions because of LVA, 18 operations because of IMR and 18 surgical corrections of VSR. In the great majority of cases a myocardial revascularization was performed simultaneously. Preoperatively the distribution of the whole patient population according to the functional NYHA classification was as follows: NYHA class I: 0, class II: 0, class III: 36 (48.6%), class IV: 27 patients (36.5%) and cardiogenic shock: 11 patients (14.9%). LVA surgery consists in aneurysmectomy and linear closure or endoventricular patch reconstruction, VSR was closed with synthetic patch material and the correction of IMR was performed mainly through partial resection and replacement with a prosthetic valve. Our early mortality was 13.1% for the LVA, 38.8% for the VSR and 11.1% for the IMR patient population, which was congruent with the rates quoted in current literature. The patient follow-up was done within a period of 6 to 90 months after discharge and the available results are very good. Late mortality was 15%. The actuarial survival rat after 7 years was 85% for the LVA, 82% for the VSR and 87% for the IMR patient population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775560 TI - Airway obstruction in neonates and children: surgical treatment. AB - OBJECTIVE: This review of 54 infants and children with airway obstruction who were treated surgically emphasizes the importance of the surgical indications with respect to various anomalies causing airway obstruction and the surgical approach to their management. PATIENTS: There were 4 etiologic groups of airway obstruction. Group A comprised 12 infants with subglottic stenosis; Group B--20 infants with tracheomalacia; 21 patients (Group C) with anatomic narrowing of the trachea; and 1 infant (Group D) with laceration of a main bronchus. METHODS: The surgical procedures performed included anterior laryngotracheal decompression in 12 infants, aortopexy in 19; 1 pulmonary arteriopexy; tracheal stenting with an autologous rib graft in 3 and with Marlex mesh in 1. Tracheal widening, using a free tibia autologous graft, was performed in 3 patients; transbronchoscopic excision in 12; anterior tracheal wedge resection in 4, and segmental tracheal resection and anastomosis in 1 patient. The lacerated bronchus was repaired with fine Dexon sutures. RESULTS: There were no operative deaths. With respect to the original indications for surgery, there were 3 failures--2 in Group A and 1 in Group C. Two patients died from causes unrelated to the procedures--one 10 days postoperatively, and the other 3 months after surgery. CONCLUSIONS: The surgical approach to tracheal obstruction in infants and children offers effective treatment, with no operative mortality, a low complication rate, and good long term survival. PMID- 7775561 TI - Geometric reconstruction in left ventricular aneurysm. Surgical aspects and early results. AB - The early results of 79 patients who underwent left ventricular aneurysmectomy with geometric and circular reconstruction in a seven-year experience are analyzed. The most common indication for operation was congestive heart failure (78.4%), either isolated (25.3%) or with angina (53.1%). Sixty patients (76%) were in NYHA class III and 10 (12.6%) in NYHA class IV at the time of surgery. Fifty-eight (73.4%) underwent coronary artery by-pass graft surgery. Hospital mortality was 5.1%, in patients older than 60 (12%), in NYHA class IV (20%), with poor left ventricular function (EF < 0.30-20% and LVED > 25) (14%), and with extensive coronary artery disease (10%) were under increased risk. Low cardiac output and use of intra-aortic balloon pump were also associated risk factors. Other risk factors mentioned in the literature are discussed. There were no deaths from isolated left ventricular aneurysmectomy. The early results of this study and the early and late results of others using the same technique are better than the results obtained in previous studies of different types of correction, suggesting that this is the procedure of choice for treating left ventricular aneurysm. PMID- 7775562 TI - Value of dobutamine/nitrate radionuclide angiography in predicting revascularization effects on ventricular function. AB - OBJECTIVE: Dobutamine and Nitrate Radionuclide Angiography (RNA) may help to distinguish viable from nonviable myocardium and to predict revascularization effects on LV function. SETTING: Ambulatory. EXPERIMENTAL DESIGN: Prospective. PATIENTS AND METHODS: We studied 12 patients (11 male, 1 female; mean age 56 +/- 10 years) with three-vessel disease, severe LV dysfunction, and prior MI for a mean follow-up time of 10 +/- 3.4 months. Thallium-201 scintigraphy favored potential viability in all patients: inducible ischemia with satisfactory perfusion in more than one coronary arterial territory. Global and regional LVEF's were calculated from preoperative RNA (baseline rest study and with continuous dobutamine infusion with gradual rate increase plus oral nitrates) and postoperative RNA at 1 and 6 months. RESULTS: There was no operative mortality, but two late deaths occurred. Symptomatically, most patients showed improvement. Global LVEF increased during dobutamine and nitrates preoperatively (p < 0.01), but not at 1 and 6 months postoperatively (without pharmacological intervention). Mean LVED volume was not significantly changed postoperatively. Regional EF improvement was found in 4 out of 9 LV wall segments under dobutamine and nitrates, and this increase persisted postoperatively at 1 and 6 months. CONCLUSIONS: Mild but significant increase in global LVEF during dobutamine and nitrates administration is not predictive of postoperative LVEF improvement. However, regional EF improvement appears to be predictive of post revascularization LV functional improvement. PMID- 7775563 TI - Crystalloid versus blood cardioplegia in coronary by-pass surgery. A prospective, randomized, controlled study in 100 consecutive adults. AB - In a prospective randomized trial we investigated the benefit of blood versus asanguinous cardioplegia in routine coronary by-pass grafting. One hundred consecutive adult patients were randomly assigned to two groups: Group A (53 patients) received cold blood cardioplegia and group B (47 patients) had standard St. Thomas solution. In all patients we combined ante- and retrograde administration, in group A warm reperfusion was carried out before aortic declamping. Aortic cross clamp times, amount of cardioplegic solution and blood potassium levels at the end of cardio-pulmonary by-pass were higher in group A than in group B. The need for inotropic support at the end of the operation as well as in the postoperative period was more frequent in the crystalloid cardioplegia group. The occurrence of atrial fibrillation showed no clear correlation to the kind of cardioplegia used. Perioperative infarction was less frequent in the blood cardioplegia group (3.7% vs 6.3%; p < 0.01) and 30-day mortality was nil (0% vs 3.2%; p < 0.01). Hospital stay did not differ between the two groups. In this clinical trial we could demonstrate the superiority of blood versus crystalloid cardioplegia in routine coronary by-pass grafting. Ante- and retrograde delivery of cold blood cardioplegia followed by warm reperfusion is a safe and simple method yielding satisfactory results. PMID- 7775564 TI - Arterial revascularisation with the conjoined double internal mammary artery grafting. AB - A free graft Internal Mammary Artery (IMA) was proximally connected end-to-side to an in-situ IMA in 6 patients, a method we have named: "The conjoined double IMA". This alternative surgical technique was applied in patients where important vessels had to be grafted in presence of diseased aortic wall, insufficient supply of adequate veins, or a mammary not long enough, thus precluding the performance of other, more conventional methods for Double IMA grafting. Early clinical and angiographic follow-up demonstrate the feasibility of this technique in selected patients. PMID- 7775565 TI - The effects on blood flows of coronary artery by-pass grafts during intra-aortic balloon pumping. AB - The internal thoracic artery (ITA), as well as aorto-coronary by-pass grafts, has been used for widely coronary artery by-pass grafting. Intra-aortic balloon pumping (IABP) is the first choice for left ventricular support when low output syndrome occurs during coronary artery by-pass surgery. However, the effect of diastolic augmentation by IABP may vary to the type of grafts. Graft flow with and without IABP support were measured in six patients undergoing elective coronary artery bypass surgery requiring IABP at Kanazawa National Hospital. The patients ranged in age from 59 to 67 years, with a mean age of 63 years, and included one woman and five men. In all cases, the left ITA was dissected from the thoracic wall as pedicle, and anastomosed in situ to the left anterior descending artery. Saphenous vein grafts (SVGs) were used for aortocoronary by pass to the obtuse marginal branches, the first diagonal branches, the left circumflex branches, and/or the right coronary artery. Blood flow in 6 ITAs, 11 SVGs to the left coronary artery systems, and three SVGs to the right coronary artery was measured by ultrasound transit-time flowmeter simultaneously with the electrocardiogram. Blood flows in ITA grafts and SVGs were measured during IABP assist and unassisting under hemodynamically stable conditions after discontinuing cardiopulmonary by-pass. The systolic and diastolic flows of each graft were measured using the peak of the R wave and the end of T wave on the electrocardiogram as the references for systole. Systolic flow during IABP were similar to unassisted flow in both ITA and SVGs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775566 TI - The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. PMID- 7775567 TI - Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope antibody delays the onset of anaphase. AB - The transition from metaphase to anaphase is regulated by a checkpoint system that prevents chromosome segregation in anaphase until all the chromosomes have aligned at the metaphase plate. We provide evidence indicating that a kinetochore phosphoepitope plays a role in this checkpoint pathway. The 3F3/2 monoclonal antibody recognizes a kinetochore phosphoepitope in mammalian cells that is expressed on chromosomes before their congression to the metaphase plate. Once chromosomes are aligned, expression is lost and cells enter anaphase shortly thereafter. When microinjected into prophase cells, the 3F3/2 antibody caused a concentration-dependent delay in the onset of anaphase. Injected antibody inhibited the normal dephosphorylation of the 3F3/2 phosphoepitope at kinetochores. Microinjection of the antibody eliminated the asymmetric expression of the phosphoepitope normally seen on sister kinetochores of chromosomes during their movement to the metaphase plate. Chromosome movement to the metaphase plate appeared unaffected in cells injected with the antibody suggesting that asymmetric expression of the phosphoepitope on sister kinetochores is not required for chromosome congression to the metaphase plate. In antibody-injected cells, the epitope remained expressed at kinetochores throughout the prolonged metaphase, but had disappeared by the onset of anaphase. When normal cells in metaphase, lacking the epitope at kinetochores, were treated with agents that perturb microtubules, the 3F3/2 phosphoepitope quickly reappeared at kinetochores. Immunoelectron microscopy revealed that the 3F3/2 epitope is concentrated in the middle electronlucent layer of the trilaminar kinetochore structure. We propose that the 3F3/2 kinetochore phosphoepitope is involved in detecting stable kinetochore-microtubule attachment or is a signaling component of the checkpoint pathway regulating the metaphase to anaphase transition. PMID- 7775568 TI - Structural interaction between the nuclear pore complex and a specific translocating RNP particle. AB - The transport of Balbiani ring (BR) premessenger RNP particles in the larval salivary gland cells of the dipteran Chironomus tentans can be followed using electron microscopy. A BR RNP particle consists of an RNP ribbon bent into a ringlike structure. Upon translocation through the nuclear pore complex (NPC), the ribbon is straightened and enters the central channel of the NPC with the 5' end of the transcript in the lead. The translocating ribbon is likely to interact with the central channel but, in addition, the remaining portion of the ribbon ring makes contact with the periphery of the NPC. To determine the nature of this latter interaction, we have now studied the connections between the RNP particle and the border of the NPC during different stages of translocation using electron microscope tomography. It was observed that the 3' terminal domain of the ribbon always touches the nuclear ring of the NPC, but the precise area of contact is variable. Sometimes also a region on the opposite side of the ribbon ring reaches the nuclear ring. The pattern of contacts could be correlated to the stage of translocation, and it was concluded that the particle-nuclear ring interactions reflect a rotation of the ribbon ring in front of the central channel, the rotation being secondary to the successive translocation of the ribbon through the channel. The particle's mode of interaction with the NPC suggests that the initial contact between the 5' end domain of the ribbon and the entrance to the central channel is probably crucial to accomplish the ordered translocation of the premessenger RNP particle through the NPC. PMID- 7775569 TI - Efficient endosomal localization of major histocompatibility complex class II invariant chain complexes requires multimerization of the invariant chain targeting sequence. AB - During biosynthesis, MHC class II-invariant chain complexes are transported into endosomal compartments where invariant chain (Ii) is degraded and class II encounters antigenic peptides. One of the signals that determines this intracellular transport route has been localized to the cytosolic domain of Ii. Deletion of this signal disrupts endosomal targeting and results in the stable expression of class II-Ii complexes at the surface. In this paper we have examined the role of Ii trimerization on the generation of this endosomal localization signal. In L cell transfectants expressing class II and both wild type Ii and a truncated form of Ii that lacks this endosomal localization signal, Ii was found to form multimers which could contain both wild type and truncated Ii. The multimers were not large aggregates but were found to be discrete complexes, probably the nine molecule class II-Ii complex that has been observed in human B cells. The co-expression of truncated Ii allowed for cell surface expression of a subset of wild type Ii. This surface-expressed wild type Ii associated with truncated Ii in multimers at a 2:1 ratio, indicating that these trimers contain two truncated and one wild type Ii molecule. These data suggest a division in trafficking of Ii trimers: if two wild type Ii molecules are present, the complex is transported to and rapidly degraded in endosomes, whereas the presence of only one wild type Ii results in trafficking and expression of the heterotrimer on the cell surface. Following surface arrival, complexes containing only a single wild type Ii molecule are internalized more rapidly and have a shorter half-life than complexes containing only truncated Ii molecules. These data suggest that although a single Ii cytosolic domain can function as a plasma membrane internalization signal, multimerization of Ii is required for efficient Golgi complex to endosome targeting of class II-Ii complexes. PMID- 7775570 TI - "Synchronized" endocytosis and intracellular sorting in alveolar macrophages: the early sorting endosome is a transient organelle. AB - Incubation of alveolar macrophages in hypoosmotic K(+)-containing buffers results in persistent cell swelling and an inability to undergo regulatory volume decrease. We demonstrate that cells incubated in hypo-K+ show an inhibition of endocytosis without any observed alteration in recycling. The inhibition of endocytosis affected all forms of membrane internalization, receptor and fluid phase. Both increased cell volume and the inhibition of endocytosis could be released upon return of cells to iso-Na+ buffers. The ability to synchronize the endocytic apparatus allowed us to examine hypotheses regarding the origin and maturation of endocytic vesicles. Incubation in hypo-K+ buffers had no effect on the delivery of ligands to degradative compartments or on the return of previously internalized receptors to the cell surface. Thus, membrane recycling and movement of internalized components to lysosomes occurred in the absence of continued membrane influx. We also demonstrate that fluorescent lipids, that had been incorporated into early endosomes, returned to the cell surface upon exposure of cells to hypo-K+ buffers. These results indicate that the early sorting endosome is a transient structure, whose existence depends upon continued membrane internalization. Our data supports the hypothesis that the transfer of material to lysosomes can best be explained by the continuous maturation of endosomes. PMID- 7775571 TI - Apical and basolateral coated pits of MDCK cells differ in their rates of maturation into coated vesicles, but not in the ability to distinguish between mutant hemagglutinin proteins with different internalization signals. AB - In polarized epithelial MDCK cells, all known endogenous endocytic receptors are found on the basolateral domain. The influenza virus hemagglutinin (HA) which is normally sorted to the apical plasma membrane, can be converted to a basolateral protein by specific mutations in its short cytoplasmic domain that also create internalization signals. For some of these mutations, sorting to the basolateral surface is incomplete, allowing internalization of two proteins that differ by a single amino acid of the internalization signal to be compared at both the apical and basolateral surfaces of MDCK cells. The rates of internalization of HA-Y543 and HA-Y543,R546 from the basolateral surface of polarized MDCK cells resembled those in nonpolarized cells, whereas their rates of internalization from the apical cell surface were fivefold slower. However, HA-Y543,R546 was internalized approximately threefold faster than HA-Y543 at both membrane domains, indicating that apical endocytic pits in polarized MDCK cells retained the ability to discriminate between different internalization signals. Slower internalization from the apical surface could not be explained by a limiting number of coated pits: apical membrane contained 0.7 as many coated pits per cell cross-section as did basolateral membranes. 10-14% of HA-Y543 at the apical surface of polarized MDCK cells was found in coated pits, a percentage not significantly different from that observed in apical coated pits of nonpolarized MDCK cells, where internalization was fivefold faster. Thus, there was no lack of binding sites for HA-Y543 in apical coated pits of polarized cells. However, at the apical surface many more shallow pits, and fewer deep, mature pits, were observed than were seen at the basolateral. These results suggest that the slower internalization at the apical surface is due to slower maturation of coated pits, and not to a difference in recognition of internalization signals. PMID- 7775572 TI - A density-sensing factor regulates signal transduction in Dictyostelium. AB - Dictyostelium discoideum initiates development when cells overgrow their bacterial food source and starve. To coordinate development, the cells monitor the extracellular level of a protein, conditioned medium factor (CMF), secreted by starved cells. When a majority of the cells in a given area have starved, as signaled by CMF secretion, the extracellular level of CMF rises above a threshold value and permits aggregation of the starved cells. The cells aggregate using relayed pulses of cAMP as the chemoattractant. Cells in which CMF accumulation has been blocked by antisense do not aggregate except in the presence of exogenous CMF. We find that these cells are viable but do not chemotax towards cAMP. Videomicroscopy indicates that the inability of CMF antisense cells to chemotax is not due to a gross defect in motility, although both video and scanning electron microscopy indicate that CMF increases the frequency of pseudopod formation. The activations of Ca2+ influx, adenylyl cyclase, and guanylyl cyclase in response to a pulse of cAMP are strongly inhibited in cells lacking CMF, but are rescued by as little as 10 s exposure of cells to CMF. The activation of phospholipase C by cAMP is not affected by CMF. Northern blots indicate normal levels of the cAMP receptor mRNA in CMF antisense cells during development, while cAMP binding assays and Scatchard plots indicate that CMF antisense cells contain normal levels of the cAMP receptor. In Dictyostelium, both adenylyl and guanylyl cyclases are activated via G proteins. We find that the interaction of the cAMP receptor with G proteins in vitro is not measurably affected by CMF, whereas the activation of adenylyl cyclase by G proteins requires cells to have been exposed to CMF. CMF thus appears to regulate aggregation by regulating an early step of cAMP signal transduction. PMID- 7775574 TI - Actin filament organization in the fish keratocyte lamellipodium. AB - From recent studies of locomoting fish keratocytes it was proposed that the dynamic turnover of actin filaments takes place by a nucleation-release mechanism, which predicts the existence of short (less than 0.5 microns) filaments throughout the lamellipodium (Theriot, J. A., and T. J. Mitchison. 1991. Nature (Lond.). 352:126-131). We have tested this model by investigating the structure of whole mount keratocyte cytoskeletons in the electron microscope and phalloidin-labeled cells, after various fixations, in the light microscope. Micrographs of negatively stained keratocyte cytoskeletons produced by Triton extraction showed that the actin filaments of the lamellipodium are organized to a first approximation in a two-dimensional orthogonal network with the filaments subtending an angle of around 45 degrees to the cell front. Actin filament fringes grown onto the front edge of keratocyte cytoskeletons by the addition of exogenous actin showed a uniform polarity when decorated with myosin subfragment 1, consistent with the fast growing ends of the actin filaments abutting the anterior edge. A steady drop in filament density was observed from the mid-region of the lamellipodium to the perinuclear zone and in images of the more posterior regions of lower filament density many of the actin filaments could be seen to be at least several microns in length. Quantitative analysis of the intensity distribution of fluorescent phalloidin staining across the lamellipodium revealed that the gradient of filament density as well as the absolute content of F-actin was dependent on the fixation method. In cells first fixed and then extracted with Triton, a steep gradient of phalloidin staining was observed from the front to the rear of the lamellipodium. With the protocol required to obtain the electron microscope images, namely Triton extraction followed by fixation, phalloidin staining was, significantly and preferentially reduced in the anterior part of the lamellipodium. This resulted in a lower gradient of filament density, consistent with that seen in the electron microscope, and indicated a loss of around 45% of the filamentous actin during Triton extraction. We conclude, first that the filament organization and length distribution does not support a nucleation release model, but is more consistent with a treadmilling-type mechanism of locomotion featuring actin filaments of graded length. Second, we suggest that two layers of filaments make up the lamellipodium; a lower, stabilized layer associated with the ventral membrane and an upper layer associated with the dorsal membrane that is composed of filaments of a shorter range of lengths than the lower layer and which is mainly lost in Triton. PMID- 7775573 TI - A trypanosome-soluble factor induces IP3 formation, intracellular Ca2+ mobilization and microfilament rearrangement in host cells. AB - Lysosomes are recruited to the invasion site during host cell entry by Trypanosoma cruzi, an unusual process suggestive of the triggering of signal transduction mechanisms. Previous studies showed that trypomastigotes, but not the noninfective epimastigotes, contain a proteolytically generated trypomastigote factor (PGTF) that induces intracellular free Ca2+ transients in several mammalian cell types. Using confocal time-lapse imaging of normal rat kidney (NRK) fibroblasts loaded with the Ca(2+)-sensitive dye fluo-3, we show that the initial intracellular free Ca(2+) concentration ([Ca2+]i) transient detected a few seconds after exposure to trypomastigote extracts is a result of Ca2+ release from intracellular stores. Removal of Ca2+ from the extracellular medium or inhibition of Ca2+ channels with NiCl2 did not affect the response to PGTF, while depletion of intracellular stores with thapsigargin abolished it. [Ca2+]i transients induced by PGTF were shown to be coupled to the activity of phospholipase C (PLC), since the specific inhibitor U73122 completely blocked the response, while its inactive analogue U73343 had no effect. In addition, polyphosphoinositide hydrolysis and inositol 1,4,5-trisphosphate (IP3) were detected upon cell stimulation with PGTF, suggesting the participation of IP3 sensitive intracellular Ca2+ channels. An immediate effect of the signaling induced by PGTF and live trypomastigotes was a rapid and transient reorganization of host cell microfilaments. The redistribution of F-actin appeared to be a direct consequence of increased [Ca2+]i, since thrombin and the Ca2+ ionophore ionomycin produced a similar effect, with a time course that corresponded to the kinetics of the elevation in [Ca2+]i. These observations support the hypothesis that PGTF-induced disassembly of the cortical actin cytoskeleton may play a role in T. cruzi invasion, by facilitating lysosome access to the invasion site. Taken together, our findings suggest that the proteolytically generated trypomastigote factor PGTF is a novel agonist that acts through the PLC/phosphoinositide signaling pathway of mammalian cells. PMID- 7775575 TI - The impact of chromosomes and centrosomes on spindle assembly as observed in living cells. AB - We analyzed the role that chromosomes, kinetochores, and centrosomes play in spindle assembly in living grasshopper spermatocytes by reconstructing spindles lacking certain components. We used video-enhanced, polarization microscopy to distinguish the effect of each component on spindle microtubule dynamics and we discovered that both chromosomes and centrosomes make potent and very different contributions to the organization of the spindle. Remarkably, the position of a single chromosome can markedly affect the distribution of microtubules within a spindle or even alter the fate of spindle assembly. In an experimentally constructed spindle having only one chromosome, moving the chromosome to one of the two poles induces a dramatic assembly of microtubules at the nearer pole and a concomitant disassembly at the farther pole. So long as a spindle carries a single chromosome it will persist normally. A spindle will also persist even when all chromosomes are detached and then removed from the cell. If, however, a single chromosome remains in the cell but is detached from the spindle and kept in the cytoplasm, the spindle disassembles. One might expect the effect of chromosomes on spindle assembly to relate to a property of a specific site on each chromosome, perhaps the kinetochore. We have ruled out that possibility by showing that it is the size of chromosomes rather than the number of kinetochores that matters. Although chromosomes affect spindle assembly, they cannot organize a spindle in the absence of centrosomes. In contrast, centrosomes can organize a functional bipolar spindle in the absence of chromosomes. If both centrosomes and chromosomes are removed from the cell, the spindle quickly disappears. PMID- 7775576 TI - Acetylation of lysine 40 in alpha-tubulin is not essential in Tetrahymena thermophila. AB - In Tetrahymena, at least 17 distinct microtubule structures are assembled from a single primary sequence type of alpha- and beta-tubulin heterodimer, precluding distinctions among microtubular systems based on tubulin primary sequence isotypes. Tetrahymena tubulins also are modified by several types of posttranslational reactions including acetylation of alpha-tubulin at lysine 40, a modification found in most eukaryotes. In Tetrahymena, axonemal alpha-tubulin and numerous other microtubules are acetylated. We completely replaced the single type of alpha-tubulin gene in the macronucleus with a version encoding arginine instead of lysine 40 and therefore cannot be acetylated at this position. No acetylated tubulin was detectable in these transformants using a monoclonal antibody specific for acetylated lysine 40. Surprisingly, mutants lacking detectable acetylated tubulin are indistinguishable from wild-type cells. Thus, acetylation of alpha-tubulin at lysine 40 is non-essential in Tetrahymena. In addition, isoelectric focusing gel analysis of axonemal tubulin from cells unable to acetylate alpha-tubulin leads us to conclude that: (a) most or all ciliary alpha-tubulin is acetylated, (b) other lysines cannot be acetylated to compensate for loss of acetylation at lysine 40, and (c) acetylated alpha-tubulin molecules in wild-type cells contain one or more additional charge-altering modifications. PMID- 7775577 TI - Structure of growing microtubule ends: two-dimensional sheets close into tubes at variable rates. AB - Observation of microtubule growth at different rates by cryo-electron microscopy reveals that the ends range from blunt to long, gently curved sheets. The mean sheet length increases with the growth rate while the width of the distributions increases with the extent of assembly. The combination of a concentration dependent growth rate of the tubulin sheet with a variable closure rate of the microtubule cylinder, results in a model in which stochastic fluctuations in sheet length and tubulin conformation confine GTP-tubulins to microtubule ends. We propose that the variability of microtubule growth rate observed by video microscopy (Gildersleeve, R. F., A. R. Cross, K. E. Cullen, A. P. Fagen, and R. C. Williams. 1992. J. Biol. Chem. 267: 7995-8006, and this study) is due to the variation in the rate of cylinder closure. The curvature of the sheets at the end of growing microtubules and the small oligomeric structures observed at the end of disassembling microtubules, indicate that tubulin molecules undergo conformational changes both during assembly and disassembly. PMID- 7775578 TI - Regulation of a muscle-specific transgene by retinoic acid. AB - Retinoic acid (RA) has been shown to have variable effects on myogenic differentiation in cell culture. The application of RA on primary cultures of embryonic somites, limb buds, and neonatal limbs inhibited myogenic differentiation in a dose-dependent way as indicated by the repression of: (a) myotube formation, (b) myosin heavy chain protein accumulation, (c) myosin light chain (MLC) 1/3, alpha sk-actin and myogenic factor transcript expression. Expression of retinoic acid receptors (RAR) was also affected by RA treatment, specifically RAR gamma transcripts were induced. To further understand the pleiotropic action of RA on myogenesis, we took advantage of two muscle-specific transgene markers which consisted of CAT reporter genes driven by regulatory elements either from the myosin light chain 1/3 locus (MLC-CAT) or the alpha skeletal actin gene (alpha sk actin-CAT). RA inhibited MLC-CAT transgene but not alpha sk actin-CAT transgene expression in primary cultures from these mice. Analysis of MLC-CAT expression in transgenic mouse primary cultures and in stably transfected C2C12 cells demonstrated that repression of MLC-CAT activity by RA was dependent upon diffusible factors in chick embryo extract. We hypothesize that during development, the pleiotropic effects of RA on myogenesis do not depend solely on the distribution and concentration of RA itself, but are also influenced by extracellular signals in the embryonic environment. PMID- 7775579 TI - Calsensin: a novel calcium-binding protein expressed in a subset of peripheral leech neurons fasciculating in a single axon tract. AB - The mAb lan3-6 recognizes a cytosolic antigen which is selectively expressed in the growth cones and axons of a small subset of peripheral sensory neurons fasciculating in a single tract common to all hirudinid leeches. We have used this antibody to clone a novel EF-hand calcium-binding protein, calsensin, by screening an expression vector library. A full-length clone of 1.1 kb identified by the antibody was isolated and sequenced. In situ hybridizations with calsensin probes and antibody staining using new polyclonal antisera generated against calsensin sequence demonstrate that calsensin indeed corresponds to the lan3-6 antigen. Calsensin consists of 83 residues with a calculated molecular mass of 9.1 kD that contains two helix-loop-helix domains. The calcium-binding domains are likely to be functional in vivo since a fusion protein derived from the calsensin clone binds 45Ca2+ in vitro. Immunoaffinity purification experiments with the lan3-6 antibody shows that a large 200,000 M(r) protein selectively copurifies with calsensin in two different leech species. These results suggest that calsensin may be functioning as a trigger protein which interacts with the larger protein. These data are consistent with the hypothesis that calsensin may mediate calcium-dependent signal transduction events in the growth cones and axons of this small group of sensory neurons which fasciculate in a single axon tract. PMID- 7775580 TI - bcl-2 overexpression inhibits cell death and promotes the morphogenesis, but not tumorigenesis of human mammary epithelial cells. AB - Overexpression of the B cell leukemia/lymphoma-2 (bcl-2) gene has been shown to confer a survival advantage on cells by inhibiting apoptosis. In epithelia, the bcl-2 gene is also related to development and differentiation, and the protein is strongly expressed in the embryo in the epithelial cells of the developing mammary gland. To investigate directly the effect of bcl-2 on human epithelial cells, we used an amphotropic recombinant retrovirus to introduce the gene into nontumorigenic cell lines developed from luminal epithelial cells cultured from milk. Here we demonstrate that while bcl-2 overexpression does not directly induce the tumorigenic phenotype, it provides a survival advantage to the mammary epithelial cells by inhibiting cell death at confluence or under conditions of serum starvation, bcl-2 can also affect the phenotype of the original epithelial cells, and promote epithelial-mesenchymal conversion, accompanied by loss of the cell adhesion molecules E-cadherin and alpha 2 beta 1 integrin. The extent of the epithelial-mesenchymal conversion varies with small differences in the phenotype of the parental line and with the level of expression of Bcl-2 and in some cases cell lines emerge with a mixed phenotype. The increased survival of Bcl-2 expressing cells at confluence results in multilayering, and the development of three- dimensional structures. Where a mixed phenotype is observed these structures consist of an outer layer of polarized epithelial cells separated by a basement membrane-like layer from an inner mass of fibroblastoid cells. Branching morphogenesis of bcl-2 transfectants is also observed in collagen gels (in the absence of fibroblast growth factors). The results strongly indicate that by increasing their survival under restrictive growth conditions, and by modifying the epithelial phenotype, bcl-2 can influence the specific morphogenetic behavior of mammary epithelial cells. PMID- 7775581 TI - The cadherin-binding specificities of B-cadherin and LCAM. AB - The cadherin family of calcium-dependent cell adhesion molecules plays an important part in the organization of cell adhesion and tissue segregation during development. The expression pattern and the binding specificity of each cadherin are of principal importance for its role in morphogenesis. B-Cadherin and LCAM, two chicken cadherins, have similar, but not identical, spatial and temporal patterns of expression. To examine the possibility that they might bind to one another in a heterophilic manner, we generated, by cDNA transfection, L-cell lines that express LCAM or B-cadherin. We then examined the abilities of these cells to coaggregate with each other and with other cadherin-expressing cells in short-term aggregation assays. The B-cadherin- and the LCAM-expressing cell lines segregate from P-, N-, or R-cadherin-expressing cells. B-cadherin- and LCAM expressing cell lines, however, appear to be completely miscible, forming large mixed aggregates. Chick B-cadherin and murine E-cadherin also form mixed aggregates, indistinguishable from homophilic aggregates. Murine E-cadherin and chick LCAM coaggregate less completely, suggesting that the heterophilic interactions of these two cell lines are weak relative to homophilic interactions. These data suggest that heterophilic interactions between B cadherin and LCAM are important during avian morphogenesis and help identify the amino acids in the binding domain that determine cadherin specificity. PMID- 7775582 TI - The interaction of the retina cell surface N acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion. AB - We have previously shown that the binding to cells of a monoclonal antibody directed against the chick neural retina N-acetylgalactosaminylphosphotransferase (GalNAcPTase) results in inhibition of cadherin-mediated adhesion and neurite outgrowth. We hypothesized that the antibody mimics the action of an endogenous ligand. Chondroitin sulfate proteoglycans (CSPGs) are potential ligands because they inhibit adhesion and neurite outgrowth and are present in situ at barriers to neuronal growth. We therefore assayed purified CSPGs for their ability to inhibit homophilic cadherin-mediated adhesion and neurite outgrowth, as well as their ability to bind directly to the GalNAcPTase. A proteoglycan with a 250-kD core protein following removal of chondroitin sulfate chains (250-kD PG) inhibits cadherin-mediated adhesion and neurite outgrowth whether presented as the core protein or as a proteoglycan monomer bearing chondroitin sulfate. A proteoglycan with a 400-kD core protein is not inhibitory in either core protein or monomer form. Treatment of cells with phosphatidylinositol-specific phospholipase C, which removes cell surface GalNAcPTase, abolishes this inhibitory effect. Binding of the 250-kD core protein to cells is competed by the anti-GalNAcPTase antibody 1B11, suggesting that 1B11 and the 250-kD core protein bind to the same site or in close proximity. Moreover, soluble GalNAcPTase binds to the immobilized 250-kD core protein but not to the immobilized 400-kD core protein. Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta catenin and the uncoupling of N-cadherin from its association with the cytoskeleton. Moreover, the 250-kD PG is present in embryonic chick retina and brain and is associated with the GalNAcPTase in situ. We conclude that the 250-kD PG is an endogenous ligand for the GalNAcPTase. Binding of the 250-kD PG to the GalNAcPTase initiates a signal cascade, involving the tyrosine phosphorylation of beta-catenin, which alters the association of cadherin with the actin-containing cytoskeleton and thereby inhibits adhesion and neurite outgrowth. Regulation of the temporal and spatial expression patterns of each member of the GalNacPTase/250-kD PG interactive pair may create opportunities for interaction that influence the course of development through effects on cadherin-based morphogenetic processes. PMID- 7775584 TI - Hepatocyte growth factor/scatter factor modulates cell motility, proliferation, and proteoglycan synthesis of chondrocytes. AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor that promotes proliferation, motility, and morphogenesis in epithelial cells. Recently the HGF receptor, c-met protooncogene product, has been shown to be expressed in developing limb buds (Sonnenberg, E., D. Meyer, M. Weidner, and C. Birchmeiyer, 1993. J. Cell Biol. 123: 223-235), suggesting that some populations of mesenchymal cells in limb buds respond to HGF/SF. To test the possibility that HGF/SF is involved in regulation of cartilage development, we isolated chondrocytes from knee joints and costal cartilages of 23-d embryonic and 4-wk-old rabbits, and analyzed the effects of HGF/SF on migration and proliferation of these cells. We found that HGF/SF stimulated migration of cultured articular chondrocytes but did not scatter limb mesenchymal fibroblasts or synovial fibroblasts in culture. HGF/SF also stimulated proliferation of chondrocytes; a maximum three-fold stimulation in DNA synthesis was observed at the concentration of 3 ng/ml of HGF/SF. Moreover, HGF/SF had the ability to enhance proteoglycan synthesis in chondrocytes. The responsiveness of chondrocytes to HGF/SF was also supported by the observation that they expressed the HGF/SF receptor. Addition of the neutralizing antibody to rat HGF/SF affected neither DNA synthesis nor proteoglycan synthesis in rat chondrocytes, suggesting a paracine mechanism of action of HGF/SF on these cells. In situ hybridization analysis showed that HGF/SF mRNA was restrictively expressed in the areas of future joint regions in developing limb buds and in the intercostal spaces of developing costal cartilages. These findings suggest that HGF/SF plays important roles in cartilage development through its multiple activities. PMID- 7775585 TI - Separate cis-acting DNA elements of the mouse pro-alpha 1(I) collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice. AB - The genes coding for the two type I collagen chains, which are active selectively in osteoblasts, odontoblasts, fibroblasts, and some mesenchymal cells, constitute good models for studying the mechanisms responsible for the cell-specific activity of genes which are expressed in a small number of discrete cell types. To test whether separate genetic elements could direct the activity of the mouse pro-alpha 1(I) collagen gene to different cell types in which it is expressed, transgenic mice were generated harboring various fragments of the proximal promoter of this gene cloned upstream of the Escherichia coli beta-galactosidase gene. During embryonic development, X-gal staining allows for the precise identification of the different cell types in which the beta-galactosidase gene is active. Transgenic mice harboring 900 bp of the pro-alpha 1(I) proximal promoter expressed the transgene at relatively low levels almost exclusively in skin. In mice containing 2.3 kb of this proximal promoter, the transgene was also expressed at high levels in osteoblasts and odontoblasts, but not in other type I collagen-producing cells. Transgenic mice harboring 3.2 kb of the proximal promoter showed an additional high level expression of the transgene in tendon and fascia fibroblasts. The pattern of expression of the lacZ transgene directed by the 0.9- and 2.3-kb pro-alpha 1(I) proximal promoters was confirmed by using the firefly luciferase gene as a reporter gene. The pattern of expression of this transgene, which can be detected even when it is active at very low levels, paralleled that of the beta-galactosidase gene. These data strongly suggest a modular arrangement of separate cell-specific cis-acting elements that can activate the mouse pro-alpha(I) collagen gene in different type I collagen producing cells. At least three different types of cell-specific elements would be located in the first 3.2 kb of the promoter: (a) an element that confers low level expression in dermal fibroblasts; (b) a second that mediates high level expression in osteoblasts and odontoblasts; and (c) one responsible for high level expression in tendon and fascia fibroblasts. Our data also imply that other cis-acting cell-specific elements which direct activity of the gene to still other type I collagen-producing cells remain to be identified. PMID- 7775583 TI - Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1. AB - Thrombospondin-1 (TSP1) has potent biological effects on vasculature smooth muscle cells (SMCs) and endothelial cells. The regulation of extracellular accumulation of TSP1 is mediated by a previously obscure process of endocytosis which leads to its lysosomal degradation. Since members of the low density lipoprotein receptor (LDLR) family have been found to mediate endocytosis which leads to degradation of a diverse array of ligands, we evaluated their possible role in the uptake and degradation of TSP1 by vascular SMCs, endothelial-cells and fibroblasts. 125I-TSP1 was found to be internalized and degraded lysosomally by all these cell types. Both the internalization and degradation of 125I-TSP1 could be inhibited by a specific antagonist of the LDLR family, the 39-kD receptor-associated protein (RAP). Antibodies to the LDLR-related protein (LRP) completely blocked the uptake and degradation of 125I-TSP1 in SMCs and fibroblasts but not endothelial cells. Solid-phase binding assays confirmed that LRP bound to TSP1 and that the interaction was of high affinity (Kd = 5 nM). Neither RAP nor LRP antibodies inhibited the binding of 125I-TSP1 to surfaces of SMCs. However, cell surface binding, as well as, endocytosis and degradation could be blocked by heparin or by pre-treatment of the cells with either heparitinase, chondroitinase or beta-D-xyloside. The data indicates that cell surface proteoglycans are involved in the LRP-mediated clearance of TSP1. A model for the clearance of TSP1 by these cells is that TSP1 bound to proteoglycans is presented to LRP for endocytosis. In endothelial cells, however, the internalization of TSP1 was not mediated by LRP but since RAP inhibited TSP1 uptake and degradation, we postulate that another member of the LDLR family is likely to be involved. PMID- 7775587 TI - Effect of lysophospholipids on signaling in the human Jurkat T cell line. AB - Lysophospholipids have recently been demonstrated to induce activation and proliferation of fibroblasts and other cell lineages by interacting with high affinity cell surface receptors leading to specific intracellular signaling events. Platelet activation, likely at the site of injury or inflammation, results in increased production of lysophospholipids suggesting a possible source of lysophospholipids. We have recently demonstrated that high concentrations of lysophospholipids are present in ascites and plasma from ovarian cancer patients, suggesting that physiologically produced lysophospholipids could interact with cells present in these fluids, including lymphocytes, and alter their function. We demonstrate herein that lysophosphatidic acid (LPA), lysophosphatidylserine (LPS), and sphingosylphosphorylcholine (SPC) activate the Jurkat T cell line. Each of the lysophospholipids induced a transient increase in cytosolic free calcium ([Ca2+]i) in Jurkat cells. Increases in [Ca2+]i were cross-desensitized by LPA, LPS and SPC, suggesting that the lysophospholipids share the same receptor(s) or that their downstream signaling pathways converge or interact. Lysophosphatidylglycerol (LPG), a competitive inhibitor of the putative LPA receptor, inhibited the calcium releasing activity of LPA, but not that of LPS and SPC, suggesting that these lysophospholipids interact with different receptors and that desensitization is due to interactions in downstream signaling pathways. The ability of the lysophospholipids to induce increases in [Ca2+]i was attenuated, but not completely blocked, by increases in [Ca2+]i induced by activation of the thrombin receptor. In contrast, increases in [Ca2+]i induced by the lysophospholipids and cross-linking the CD3 component of the T cell receptor complex with the UCHT1 antibody did not undergo heterologous desensitization. Strikingly, LPA is sufficient to stimulate proliferation of Jurkat cells in serum free medium or in synergy with low concentrations of fetal bovine serum. In addition, LPA also increased the production of the T cell growth factor, interleukin 2 (IL-2), by Jurkat cells treated with phorbol esters. LPS, in contrast, inhibited Jurkat proliferation while increasing IL-2 production and SPC inhibited both processes. Thus, although all three lysophospholipids were sufficient to induce a transient increase in [Ca2+]i in Jurkat cells, they induced markedly different physiological consequences. PMID- 7775586 TI - Patterns of cyclic AMP-dependent protein kinase gene expression during ontogeny of the murine palate. AB - Normal growth and differentiation of embryonic palatal tissue depends on regulated levels of intracellular cAMP. Cyclic AMP-dependent protein kinases (PKA) act to mediate the biological activities of cAMP. PKA isozyme protein profiles demonstrate a clear pattern of temporal alterations in embryonic palatal tissue during its development. In order to ascertain the molecular basis for changing PKA isozyme profiles during palatal ontogeny, the spatial and temporal expression of mRNAs for regulatory (RI alpha, RII alpha, and RII beta) and catalytic (C alpha) subunits of PKA was examined. RNA extracted from murine embryonic palatal tissue (days 12-14 of gestation) was examined by Northern blot analysis. Significant levels of constitutively expressed RI alpha and C alpha mRNA were seen on all days of gestation examined. RI alpha transcripts were substantially less abundant in palate mesenchymal cells in vitro than in palatal tissue in vivo. Levels of RII alpha and RII beta mRNA were highest on gestational day (GD) 12, a period characterized by pronounced palatal tissue growth. In addition, patterns of tissue distribution of RII beta, not previously described, were examined in the developing embryonic palate. A dramatic developmental shift in tissue distribution of RII beta was seen. The isozyme was evenly distributed between palatal epithelial and mesenchymal cells on GD 12 but by GD 14, RII beta was predominantly localized to palatal epithelial cells. Direct activation of adenylate cyclase with forskolin in murine embryonic palate mesenchymal (MEPM) cells resulted in an increase in RII alpha mRNA levels but had no effect on steady state levels of RII beta or C alpha mRNA. In addition, elevation of intracellular levels of cAMP resulted in a shift in the transcriptional profile of RI alpha mRNAs. Results of this study document specific patterns of expression for the genes encoding the various cAMP-dependent protein kinase regulatory and C alpha subunits in murine embryonic palatal tissue. In addition, we have demonstrated adaptational changes of this kinase in MEPM cells in response to conditions of increased intracellular levels of cAMP. PMID- 7775588 TI - Matrix protein synthesis by glomerular mesangial cells in culture: effects of transforming growth factor beta (TGF beta) and platelet-derived growth factor (PDGF) on fibronectin and collagen type IV mRNA. AB - The pathogenesis of glomerular scarring is multifactional; recent evidence suggests that transforming growth factor beta (TGF beta), a pleiotropic cicatricial mediator, may promote mesangial sclerosis by enhancing the production of extracellular matrix proteins. We studied the effect of TGF beta 1 and TFG beta 2 on collagen type IV and fibronectin (FN) synthesis in human glomerular mesangial cells in culture (GMC). Two hours after addition of TGF beta, an up to twofold increase in abundance of collagen type IV mRNA was found, which further increased up to fivefold within 24 h. Addition of cycloheximide did not inhibit the TGF beta effect, but caused by itself an up to twofold increase in the abundance of collagen type IV mRNA after 2 h. Together with collagen mRNA, the mRNA for FN and for platelet-derived growth factor (PDGF) was also enhanced. PDGF was found to enhance abundance of the collagen type IV and fibronectin mRNA in GMC. A neutralizing antibody to PDGF or a PDGF-antisense oligonucleotide partly inhibited the TGF beta-induced increase of collagen type IV mRNA, suggesting that TGF beta can affect the collagen type IV synthesis not only directly but also indirectly via the synthesis of PDGF. PMID- 7775589 TI - Effects of the overexpression of the small heat shock protein, HSP27, on the sensitivity of human fibroblast cells exposed to oxidative stress. AB - The role of the human small heat shock protein (HSP27) in oxidative stress was examined using stable transformants of an immortalized human fibroblast cell line (KMST-6) isolated by transfection of HSP27 expression vectors. Several stable transformants that expressed high or low levels of HSP27 protein were obtained. Clones expressing high levels of HSP27 were more sensitive to growth inhibition by a low dose of hydrogen peroxide (0.1 mM) than those expressing low levels. Clones expressing high levels of HSP27 did not acquire obvious resistance to hyperthermy and cytotoxic agents, except for one (#13), in which resistance to cytotoxic agents was increased. The level of phosphorylated HSP27 in clones expressing high levels of this protein increased at 30 min and was sustained even 4 hours after exposing the cells to 0.1 mM of hydrogen peroxide. On the other hand, the levels in clones expressing low levels of HSP27 were reduced within 4 hours after exposure to hydrogen peroxide. Furthermore, overexpression of nonphosphorylatable mutant HSP27 did not affect sensitivity to oxidative stress. These results suggested that constitutively high expression of HSP27 in KMST-6 cells make them susceptible to oxidative stress resulting in growth arrest, and this mechanism could involve the phosphorylation of HSP27. PMID- 7775591 TI - Iron and copper requirements for proliferation and differentiation of a human promyelocytic leukemia cell line (HL-60). AB - Trace mineral deficiencies tend to have profound effects on the integrity of formed blood elements. Anemia and neutropenia are commonly seen in copper (Cu) deficiency. We therefore developed a serum-free medium to examine the trace mineral requirements, in particular iron and Cu, for proliferation and retinoic acid (RA)-induced differentiation of HL-60 cells. This defined medium (DFM) was composed of Iscove's Modified Dulbecco's Medium (IMDM) supplemented with insulin and human apo-transferrin (each at 5 micrograms/ml) and 1.4 microM FeSO4. The iron concentration range for optimal cellular proliferation was narrow (2-3 microM). HL-60 cells could be maintained in DFM for 15 passages with a doubling time of 38-40 hr. The Cu content of IMDM was very low. Thus, by the fourth passage in DFM, the activity of cuproenzymes (cytochrome c oxidase, CCO; and copper-zinc superoxide dismutase, CuZnSOD) began to decline. Supplementation of DFM with CuSO4 (50 nM) restored enzyme activities. Treatment of cells with a Cu chelator (tetrathiomolybdate, 1 microM) rapidly reduced the activities of both CCO and CuZnSOD. Over the Cu concentration range examined (5-350 nM), Cu supplementation had little effect on HL-60 proliferation. Cell retained the ability to differentiate along the granulocytic pathway when treated with RA, but seemed to be less sensitive to the inducing agent except at the highest concentration tested (1 microM). This decreased sensitivity to RA did not seem to be related to the Cu status of the cells but rather to the absence of a component of serum. Indeed, cells grown in DFM regained their sensitivity to RA when allowed to differentiate in IMDM with 5% serum. These data indicate that the processes of growth and terminal differentiation in HL-60 cells are not greatly influenced by Cu. Thus, it seems likely that the insult resulting in neutropenia which is associated with Cu deficiency may occur earlier than the promyelocytic stage. However, the possibility that the mechanisms contributing to neutropenia may be unrelated to primary defects in the biochemistry of neutrophil maturation cannot be ruled out. PMID- 7775590 TI - Evidence that cell survival is controlled by interleukin-3 independently of cell proliferation. AB - Hemopoietic cell proliferation is controlled by a set of polypeptide growth factors and regulatory molecules that bind to cell surface receptors inducing cellular responses. Maintenance of a viable state, cell growth, DNA synthesis and mitosis are basic properties of proliferating cells, but links between growth factor receptors and each of these cellular outcomes are poorly understood. Most studies have monitored DNA synthesis as a measure of progression through the cell cycle or directly measured viable cell numbers, but cell survival per se as an output of receptor activation by ligand, has received little attention. In this study we have used a bone marrow-derived murine cell line that is dependent on interleukin-3 for growth, to investigate the relationship between DNA synthesis and a biochemical marker of cell survival, reduction of the tetrazolium salt, MTT. We show that at times up to 6 hr, continued DNA synthesis, RNA synthesis, protein synthesis, and mitochondrial respiration are not necessary for background or IL-3-stimulated MTT reduction. Furthermore, dibutyryl cyclic AMP promoted background and IL-3-dependent MTT reduction while simultaneously inhibiting DNA synthesis. These results provide evidence that IL-3 controls events involved in MTT reduction and cell survival independently of DNA synthesis. PMID- 7775592 TI - Immunochemical characterisation of megakaryocyte potentiator activity from mouse bone marrow. AB - Megakaryocyte potentiator derived from mouse bone marrow has been shown to be immunologically similar to Interleukin-6 (IL-6). In this study the activity has been characterised by biochemical and immunochemical techniques. The activity is described as a O-linked glycosylated molecule with an apparent MW of 15 Kd and pl of the range pH 5.9-6.35. The data show that mouse bone marrow potentiator activity is a variant of IL-6 and with the potential to enhance megakaryocyte growth. PMID- 7775593 TI - RB phosphorylation in sodium butyrate-resistant HL-60 cells: cross-resistance to retinoic acid but not vitamin D3. AB - To examine the potential coupling between inducible cellular changes in RB (retinoblastoma) tumor suppressor protein phosphorylation and ability to G0 growth arrest and differentiate, HL-60 promyelocytic leukemia cells were cultured in incremental sodium butyrate (NaB) concentrations and thereby made resistant to the growth inhibitory effects of sodium butyrate, which normally induces G0 arrest and monocytic differentiation in wild type HL-60 cells. The resistant cells were also unable to differentiate in response to NaB, indicating that a regulatory function controlling both G0 growth arrest and differentiation had been affected. The induced resistance was not genetic in origin since the cells regained the ability to G0 arrest and differentiate after being recultured in medium free of sodium butyrate for only three days. The resistant cells had similar cell cycle phase durations as the original wild type cells. The resistant cells retained the ability to both G0 arrest and differentiate in response to 1,25-dihydroxy vitamin D3 (VD3), normally an inducer of G0 arrest and monocytic differentiation in wild type cells. However, they were cross-resistant to retinoic acid (RA), another ligand for the same steroid thyroid hormone receptor family, which induces G0 arrest and myeloid differentiation in wild type cells. The ability to G0 arrest and phenotypically differentiate in response to RA were both grossly impaired. Unlike wild type cells which undergo early down-regulation and then hypophosphorylation of the RB protein when induced to differentiate, in resistant cells, hypophosphorylation of RB in response to NaB was grossly retarded. These changes in RB protein occurred faster when the cells were treated with VD3. In contrast, the changes in RB phosphorylation occurred significantly slower when the cells were treated with RA. The results suggest a coupling between the ability to G0 growth arrest and phenotypically convert and the ability to hypophosphorylate RB. PMID- 7775594 TI - Regulation of endothelial cell gap formation and barrier dysfunction: role of myosin light chain phosphorylation. AB - Endothelial cell (EC) contraction results in intercellular gap formation and loss of the selective vascular barrier to circulating macromolecules. We tested the hypothesis that phosphorylation of regulatory myosin light chains (MLC) by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) is critical to EC barrier dysfunction elicited by thrombin. Thrombin stimulated a rapid (< 15 sec) increase in [Ca2+]i which preceded maximal MLC phosphorylation (60 sec) with a 6 to 8-fold increase above constitutive levels of phosphorylated MLC. Dramatic cellular shape changes indicative of contraction and gap formation were observed at 5 min with maximal increases in albumin permeability occurring by 10 min. Neither the Ca2+ ionophore, A23187, nor phorbol myristate acetate (PMA), a direct activator of protein kinase C (PKC), alone or in combination, produced MLC phosphorylation. The combination was synergistic, however, in stimulating EC contraction/gap formation and barrier dysfunction (3 to 4-fold increase). Down regulation or inhibition of PKC activity attenuated thrombin-induced MLC phosphorylation (approximately 40% inhibition) and both thrombin- and PMA-induced albumin clearance (approximately 50% inhibition). Agents which augmented [cAMP]i partially blocked thrombin-induced MLC phosphorylation (approximately 50%) and completely inhibited both thrombin- and PMA-induced EC permeability (100% inhibition). Furthermore, cAMP produced significant reduction in the basal levels of constitutive MLC phosphorylation. Finally, MLCK inhibition (with either ML-7 or KT 5926) or Ca2+/calmodulin antagonism (with either trifluoperazine or W-7) attenuated thrombin-induced MLC phosphorylation and barrier dysfunction. These results suggest a model wherein EC contractile events, gap formation and barrier dysfunction occur via MLCK-dependent and independent mechanisms and are significantly modulated by both PKC and cAMP-dependent protein kinase A activities. PMID- 7775596 TI - Growth of mouse hepatocytes is stimulated by gastrin. AB - Hepatocyte growth is regulated by various growth factors, including epidermal growth factor (EGF) and insulin. Recently, several additional peptide hormones have been shown to stimulate growth of hepatocyte only in the presence of EGF or insulin and are thus termed secondary mitogens. Gastrin regulates growth of normal and neoplastic gastrointestinal tissues, but the effect on growth of hepatocyte is unknown. We examined the effect of gastrin on growth of a normal mouse hepatocyte (NMH) line established in our laboratory. Effect of gastrin-17 (G-17) (10(-8) to 10(-6) M) on growth of NHM cells was examined in either the presence or absence of EGF in the culture medium. Growth of NMH cells was evaluated by incorporation of either bromodeoxyuridine (BrdU) or 3H-thymidine and by counting cells. Presence of a cell-surface receptor for G-17 was determined by Scatchard analysis using 125I-G-17. In the presence of EGF, gastrin stimulated growth of NMH cells; in the absence of EGF, gastrin did not affect growth. The stimulatory effect of gastrin on NMH cells was blocked by JMV 320, a CCK-B type receptor antagonist. NMH cells possess a single, high affinity binding site for gastrin (Kd = 1.2 nM); EGF increased the gastrin binding capacity compared to non treated cells (3.5 +/- 0.4 vs. 2.2 +/- 0.6 fmol/10(6) cells). G-17 stimulated growth of NMH cells through a single high affinity receptor for G-17 which pharmcologically appears to be the CCK-B type only in the presence of EGF and thus can be considered a secondary mitogen. PMID- 7775595 TI - Inhibition of N-linked glycosylation induces early apoptosis in human promyelocytic HL-60 cells. AB - Inhibition of protein N-glycosylation by tunicamycin induced morphological changes characteristic of apoptosis in human promyelocytic HL-60 cells. Internucleosomal DNA fragmentation could be detected after short-time incubation (between 6 and 9 h) of HL-60 cells with low doses of tunicamycin (0.05 micrograms/ml). Under these conditions the synthesis of glycoproteins was reduced to 17% of control values, while no significant changes in the rates of total protein synthesis could be observed. Tunicamycin ability to induce DNA fragmentation was in good correlation with its potency as glycosylation inhibitor in several myeloid cell lines. Tunicamycin-induced apoptosis was potentiated by activation of protein kinease C (PKC) by phorbol esters and partially prevented by the PKC inhibitor staurosporine. Inhibitors of RNA and protein synthesis displayed a protective effect. Treatment of HL-60 cells with tunicamycin did not elicit the expression of cell surface differentiation antigens or their ability to generate superoxide anion. In contrast, tunicamycin significantly inhibited these processes during dimethyl sulfoxide (DMSO)-induced myeloid differentiation. These observations indicate that the main effect of tunicamycin in HL-60 cells is the induction of apoptosis. PMID- 7775597 TI - P-glycoprotein stability is affected by serum deprivation and high cell density in multidrug-resistant cells. AB - The control of P-glycoprotein (Pgp) expression in multidrug-resistant cells (MDR) is complex and may be regulated at different levels. We have investigated Pgp stability in four different human and hamster MDR cell lines. Using a pulse-chase procedure we show that Pgp half-life is between 14 and 17 h in all these cell lines when they are growing exponentially. However, in the presence of a low level of serum, Pgp half-life is increased four to sixfold. A similar effect is observed when the cell cultures are maintained in high cell density. The increased Pgp stability appears to be differently regulated as serum deprivation results in a general enhanced degradation of total cytoplasmic and membrane proteins. Moreover, the observed serum effect suggests the involvement of growth factors in the control of Pgp stability. These findings suggest that protein stability may be an important factor in the regulation of Pgp expression. PMID- 7775598 TI - Multifunctional phosphatidic acid signaling in mammary epithelial cells: stimulation of phosphoinositide hydrolysis and conversion to diglyceride. AB - We have shown previously that phosphatidic acid esterified to polyunsaturated fatty acids is mitogenic for primary cultures of mouse mammary epithelial cells embedded within collagen gels. We hypothesized that this mitogenic competence resulted from the ability of this phospholipid to activate multiple signal transduction pathways in mammary epithelium. A closer examination of this hypothesis was undertaken by examining the effect of exogenous phosphatidic acid on phosphoinositide (PI) hydrolysis and its intracellular metabolism to diglyceride, an activator of protein kinase C. For assays of phosphoinositide specific phospholipase C activation, mammary epithelial cells from virgin Balb/c mice were isolated by collagenase dissociation of mammary glands and cultured on the surface of Type I collagen-coated culture dishes. Phosphatidic acid (PA) stimulated a sustained increase in inositol phosphates and caused inositol phospholipid depletion when added to cells in which inositol phospholipids were prelabeled with 3H-myoinositol. This effect was specific for PA among phospholipids tested. Neither lineoleic acid, that can be released from PA, nor prostaglandin E2 affected PI hydrolysis. When mammary epithelial cells were cultured inside collagen gels in the presence of exogenous PA or phosphatidylcholine (PC) radiolabeled with 3H-glycerol, PA was found to persist intracellularly and be dephosphorylated to diglyceride (an activator of protein kinase C) to a greater extent than PC, a nonmitogenic phospholipid. In contrast to PA, epidermal growth factor (EGF) only slightly stimulated PI hydrolysis, showing that these two different growth-promoting factors do not actively couple to the same signal transduction pathways in mammary epithelial cells. These results show that PA may activate multiple pathways in mammary epithelial cells either directly or via its metabolism to diglyceride. PMID- 7775599 TI - Multiple pathways are involved in protection of MCF-7 cells against death due to protein synthesis inhibition. AB - Previously we have shown that IGF-I protected MCF-7 cells against death induced by the protein synthesis inhibitor cycloheximide (CHX). In the present study we investigated the ability of protein kinase C activator 12-0-tetradecanoyl-phorbol 13-acetate (TPA), the protein kinase A activator 8-bromoadenosine 3'5'-cyclic monophosphate (Br-cAMP), and the enzyme inhibitor aurintricarboxylic acid (ATA) to protect MCF-7 cells against death, due to a continuous presence of CHX. Cell death was evaluated after 48 h of incubation by several techniques (trypan blue staining, release of lactic dehydrogenase, cellular ATP content, transmission electron microscopy, and DNA fragmentation). Apoptosis which terminates in necrosis, characterized this mode of cell death. TPA and ATA at optimal concentrations of 40 ng/ml and 100 micrograms/ml, respectively, reduced cell death to the control level (without CHX), while Br-cAMP at an optimal concentration of 650 micrograms/ml reduced cell death only partially. IGF-1, TPA, and ATA, which stimulated protein synthesis in the control MCF-7 cells, had no effect on protein synthesis in the CHX-treated cells, indicating that the survival effect is not due to new protein synthesis. The protein kinase C inhibitor staurosporine blocked the survival effect of TPA and IGF-1 in a dose dependent manner, however did not affect the survival effect of ATA. The tyrosine kinase inhibitor genistein blocked the survival effect of IGF-1, but not that of TPA and ATA. Our results provide evidence for several distinctive pathways, the activation of which protects MCF-7 cells against death, due to protein synthesis inhibition. PMID- 7775600 TI - Cell cycle reentry of mammalian fibroblasts is accompanied by the sustained activation of p44mapk and p42mapk isoforms in the G1 phase and their inactivation at the G1/S transition. AB - Mitogen-activated protein (MAP) kinases are serine/threonine kinases that are rapidly activated in response to mitogenic stimuli. Here we examined the enzymatic activity and phosphorylation state of the individual p44mapk and p42mapk isoforms during early G1 and late G1 phase of the mammalian cell cycle. Release of fibroblast cells from early G1 block was accompanied by a rapid rise in the myelin basic protein (MBP) kinase activity of p44mapk and p42mapk, which declined slowly over several hours to reach negligible values as cells enter S phase. When cells were released from late G1 block, the activity of p44mapk and p42mapk increased transiently, and then rapidly declined to baseline values during G1 to S phase transition. Cells released at the G1/S boundary in a medium lacking growth factors entered S phase in the complete absence of MAP kinase activity. Unlike MAP kinases, the histone H1 kinase activity of p33cdk2 was elevated in late G1 arrested cells and continued to increase during S phase entry. The enzymatic activation of p44mapk and p42mapk in both early G1 and late G1 phase was accompanied by an increase in the phosphothreonine and phosphotyrosine content of the proteins. These findings suggest that the sustained activation of MAP kinases during G1 progression and their inactivation at the G1/S transition are two regulatory processes involved in the mitogenic response to growth factors. PMID- 7775601 TI - Mitogenic activity of neu differentiation factor/heregulin mimics that of epidermal growth factor and insulin-like growth factor-I in human mammary epithelial cells. AB - Recently, a family of growth factors has been described that activates erbB-2 receptors. These factors, known as the neu differentiation factors (NDF) or heregulins (HRG), induce tyrosine phosphorylation of erbB-2 receptors as a result of their direct interaction with either erbB-3 or erbB-4 receptors. Although it is known that expression of erbB-2 receptors has relevance in human breast cancer progression, how erbB-2, -3 and -4 receptors regulate mammary epithelial cell proliferation is not known. Therefore, experiments were carried out to study the mitogenic activity of NDF/HRG on the human mammary epithelial cell line MCF-10A which can be cultured continuously under serum-free conditions. MCF-10A cells, like primary cultures of normal human mammary epithelial cells, express an absolute requirement for exogenous epidermal growth factor (EGF) and insulinlike growth factor I (IGF-I) for growth. The results of these experiments indicate that NDF/HRG can induce tyrosine phosphorylation of p185erbB-2 in MCF-10A cells and is mitogenic for these cells. This is consistent with the coexpression of erbB-2 and erbB-3 mRNA that we have observed in MCF-10A cells. In addition, we found that NDF/HRG can substitute for either EGF or IGF-I to stimulate proliferation of these cells. The ability to substitute for both EGF and IGF-I is a unique property of NDF/HRG and is not shared by other members of the EGF or IGF family of growth factors, nor by other factors that we have studied. A striking isoform specificity was also observed which indicated that the beta-isoforms of NDF/HRG were greater than ten times more mitogenic than the alpha-isoforms. We also examined the mitogenic activity of NDF/HRG on MCF-10A cells that overexpress the erbB-2 receptor as a result of infection with a retroviral vector containing the human c-erbB-2 gene (MCF-10AerbB-2 cells). These studies indicated that MCF 10AerbB-2 cells have increased sensitivity to the mitogenic effects of NDF/HRG and that these cells are responsive to the alpha-isoforms of NDF/HRG at physiological concentrations. Thus, NDF/HRG is a dual specificity growth factor for human mammary epithelial cells, and the responsiveness of the cells to NDF/HRG is influenced by the level of expression of erbB-2 receptors. PMID- 7775602 TI - Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cells in response to various melanogenesis regulatory agents. AB - Tyrosinase is the rate limiting enzyme critically associated with melanin synthesis. The melanosomes are specialized membrane-bound organelles within melanocytic cells in which melanin polymers are ultimately deposited. To determine whether tyrosinase correlates with the number of melanosomes, we examined the relationship between tyrosinase activity, tyrosinase mRNA levels, and the number of melanosomes in B16 murine melanoma cells, using melanogenesis regulatory agents. 12-O-Tetradecanoylphorbol-13-acetate (TPA) or linoleic acid decreased tyrosinase activity, while dibutyryl cyclic adenosine monophosphate (dbcAMP) or palmitic acid increased it. The tyrosinase mRNA levels were not always correlated with tyrosinase activity, i.e., TPA down-regulated, dbcAMP upregulated, while linoleic acid or palmitic acid did not alter the message levels, indicating that fatty acid regulation of melanogenesis was due to post transcriptional events. The number of melanosomes changed when agents which modulate the tyrosinase gene expression were added, since TPA decreased, dbcAMP increased, and linoleic acid or palmitic acid did not alter their number. These results suggest that the number of melanosomes changed in relation to tyrosinase mRNA level but not to tyrosinase activity in response to melanogenesis regulatory agents. PMID- 7775603 TI - Differential effects of glucocorticoids on insulin-like growth factor I action in cultured human fibroblasts. AB - Glucocorticoids act synergistically with insulin-like growth factor I (IGF-I) to stimulate DNA synthesis and replication of cultured human fibroblasts. In the present study, we further define glucocorticoid and IGF-I interactive effects on human fibroblast metabolism and growth. IGF-I stimulated dose-dependent increases in early metabolic events. Half-maximal effectiveness was seen at 5-8 ng/ml IGF I, with mean maximal responses of 1.5-, 2-, and 6-fold for [3H]2-deoxyglucose uptake, [14C]glucose incorporation, and [14C]aminoisobutyric acid (AIB) uptake, respectively. A 48-hour preincubation with 10(-7) M dexamethasone markedly enhanced both the sensitivity and maximal effectiveness of IGF-I stimulation of AIB uptake. In contrast, dexamethasone had no effect on IGF-I-stimulated glucose uptake and utilization. Maximum specific binding of [125I]IGF-I to fibroblast monolayers was identical in ethanol control and glucocorticoid-treated cells, with 50% displacement at approximately 5 ng/ml IGF-I. In addition to its synergism with IGF-I, preincubation with dexamethasone augmented insulin and epidermal growth factor (EGF) stimulation of [3H]thymidine incorporation; dexamethasone had no effect on platelet-derived growth factor or fibroblast growth factor action. Two-dimensional gel electrophoresis identified two specific glucocorticoid-induced proteins in human fibroblast cell extracts with molecular weights of 45K and 53K and pIs of 6.8 and 6.3, respectively. These data indicate that IGF-I receptor-mediated actions in human fibroblasts are differentially modulated by glucocorticoids. Glucocorticoids are synergistic with IGF-I in stimulating mitogenesis and amino acid uptake, without having any apparent effect on IGF-I-stimulating glucose metabolism. Glucocorticoid enhancement of growth factor bioactivity may involve modulation of a regulatory event in the mitogenic signaling pathway subsequent to cell surface receptor activation. PMID- 7775604 TI - Activation of junB and c-myc primary response genes by interleukin 9 in a human factor-dependent cell line. AB - Interleukin 9 (IL-9) stimulates the proliferation of various hematopoietic cell types. To elucidate the molecular mechanisms underlying the cell proliferation action, immediate-early gene expression elicited by IL-9 in a human factor dependent cell line, MO7e, was studied. IL-9 stimulation resulted in a rapid and transient elevation of primary response genes including junB and c-myc. The differential effects of protein kinase inhibitors, herbimycin A, genistein, and H 7 on the steady-state mRNA level and the transcription rate of junB and c-myc genes triggered by IL-9 were also investigated. Herbimycin A, but not genistein, specifically inhibited the expression of junB steady-state mRNA and the in vitro transcription of the junB gene. IL-9-enhanced c-myc gene expression was completely inhibited by both herbimycin A and genistein at the level of transcriptional initiation. H-7 failed to inhibit c-myc, but partially abolished junB mRNA induction. The role of protein kinase C in IL-9-mediated junB induction was also examined. The different responses of junB and c-myc messages to protein kinase inhibitors suggested that more than one pathway may be involved in IL-9 mediated signal transduction which leads to the expression of junB and c-myc genes. PMID- 7775605 TI - Isolation of nonsedimentable lipid-protein particles from insect intestine. AB - Nonsedimentable lipid-protein particles have been isolated from intestinal tissue of the American cockroach, Periplaneta americana. Most of the particles were within the range 30-50 nm in diameter and appear to originate from larger structures. Lipid analysis of the particles showed them to be enriched in neutral lipid components relative to microsomal membranes. Specifically, there is a decline in the amounts of phosphatidylcholine and phosphatidylethanolamine in the nonsedimentable particles compared with the microsomal membranes. Also, in contrast to microsomal membranes, the particles have a higher content of phosphatidic acid along with 1,2- and 1,3-diacyglycerols, free fatty acids and an unidentified lipid that co-migrates with sterol ester, wax ester and hydrocarbon standards in thin layer chromatograms. The cytosol, separated from the particles by ultrafiltration, contained phosphatidic acid, free fatty acids and the unidentified lipid. By contrast, the composition of neutral lipids in the cytosol resembles that of the particles. SDS-PAGE analysis of microsomal membranes, the particles and particle free cytosol shows an enrichment of low molecular weight proteins in the particles and cytosol. The particles and cytosol appear to possess proteolytic activity that is distinguishable from that of corresponding microsomal membranes since the incubation of these components with BSA resulted in the formation of distinct polypeptides. Many characteristics of these particles resemble those of the deteriosomes that have been isolated from plant tissue. PMID- 7775606 TI - Analysis of sequence-specific binding activity of cis-elements in human thymidine kinase gene promoter during G1/S phase transition. AB - Expression of thymidine kinase (TK) gene in normal human diploid, cells is both cell cycle and age dependent and appears to be transcriptionally regulated. Several studies have indicated that the G1/S control sequence may reside within the region of about 130 bp upstream of the transcription initiation site. We have previously shown that a trans-acting factor, CBP/tk (CCAAT binding protein for TK gene), binds to either one of the two inverted CCAAT boxes in a cell cycle- and age-dependent manner (Pang and Chen, 1993, J. Biol. Chem., 268:2909-2916). An upstream 25 bp fragment (-109/-84), containing both Yi-like and E2F-like binding sites, has recently been proposed to be essential for the G1/S regulation of human TK gene. To assess the contribution of various cis-elements in human TK promoter to the G1/S regulation, we have examined the binding activity of these cis-elements in the nuclear extracts derived from human IMR-90 cells at low passage number. Our results indicated that no binding activity could be detected using either the 25 bp fragment (-109/-94) or the authentic Yi sequence. However, Yi binding activity was observed in SV-40 transformed IMR-90 cells. In contrast, the 28 bp fragment (-91/-64) that contains the distal inverted CCAAT box exhibited a strong binding in serum-stimulated young IMR-90 cells. The binding of CBP/tk to the 28 bp fragment was abolished by a single base mutation in the CCAAT box. The CBP/tk binding of the 28 bp fragment could not be displaced by either the 25 bp fragment or the authentic Yi element. A deletion of the 5'-flanking region of the 28 bp fragment up to 5 bases also abolished the binding activity. The CBP/tk binding in IMR-90 cells was supershifted by antiserum against NF-Ya, but not by antiserum made against p107, pRb, cyclin A, p33cdk2, or p34cdc2. Taken together, our results suggest that the G1/S regulatory cis-element in human TK promoter may be confined only to CBP/tk binding sites. PMID- 7775607 TI - XVII international Symposium on Cerebral Blood Flow and Metabolism. Cologne, Germany, 2-6 July 1995. Abstracts. PMID- 7775608 TI - Medicine as an agency of social control: Part Three. PMID- 7775609 TI - Effects of water deprivation for 48 hours on the pharmacokinetics and pharmacodynamics of furosemide in rats. AB - The effects of water deprivation for 48 h on the pharmacokinetics and pharmacodynamics of furosemide were examined after intravenous, 8 mg/kg body weight, and oral administration, 16 mg/kg body weight, of furosemide to control and water deprived rats. After i.v. administration, the total body and nonrenal clearances decreased significantly in water-deprived rats. The urine output, urinary excretion of sodium, potassium and chloride based on grams of kidney weight, and the diuretic, natriuretic and chloruretic efficiencies decreased significantly in water-deprived rats after both intravenous and oral administration of furosemide, suggesting that the dose of furosemide for water deprived patients may require modification. PMID- 7775610 TI - Caffeine test assessment for measuring liver function in critically ill patients. AB - Caffeine elimination was studied in 73 patients admitted to an intensive care unit, 33 of whom had liver disease. Mean plasma clearance of caffeine in patients with no liver disease (1.30 +/- 0.79 ml/kg/min) was significantly higher than in patients with liver disease (0.39 +/- 0.23 ml/kg/min). Mean half-life of caffeine in patients with liver disease (23.96 +/- 12.19 h) was significantly higher than in patients with no liver disease (7.25 +/- 3.04 h). No significant differences in distribution volumes were found. Receptor-operator curves (ROC) for plasma clearance and the half-life of elimination of caffeine showed a high diagnostic value. Therefore, the parameters for caffeine biotransformation, i.e. Cl and t1/2, are useful for assessing liver function in the population studied. PMID- 7775612 TI - Patient information leaflets on over-the-counter (OTC) medicines: the manufacturer's perspective. AB - A survey was undertaken to assess the views of the manufacturers of over-the counter (OTC) products about (i) the value of patient information leaflets (PILs), (ii) the recent European Community directive relating to PILs and (iii) the procedures which are in place for producing and testing PILs. Although approximately half (15/31) of the respondents (response rate 31/58) thought that PILs were more important for OTC than prescription only medicines, this view was not unanimous. A majority (18/28) thought that the new EC directive would provide too much information to patients although only a small number (2/27) thought that the regulations were unnecessary. Indication for the product was thought to be the most important information for the immediate outer packaging. Only about one third (35%) of patients are thought to read PILs, in contrast to the majority who read the outer packaging. A wide variety of departments contribute to preparing PILs. The marketing department had a major input particularly with respect to layout and testing of leaflets. On the whole the design and production of PILs involves considerable effort but their testing appears less structured and thorough. PMID- 7775611 TI - The medical and surgical management of trigeminal neuralgia. AB - Trigeminal neuralgia is a paroxysmal and severely disabling facial pain. The diagnosis is usually made on the basis of a typical history and the exclusion of secondary causes. Initial management of the pain is medical. Carbamazepine is the drug of choice although some patients respond to other drugs including phenytoin, baclofen, sodium valproate and clonazepam. Surgical therapy should be considered if medical treatment fails or cannot be tolerated. Surgical options include peripheral or central (intracranial) procedures. Central procedures have greater morbidity and a significant mortality rate (approximately 1%) but the success rates are much greater. Physicians should be aware of the potential benefits of surgery but all patients should be advised carefully about the risks before informed consent is given. PMID- 7775614 TI - Prolonged bleeding time during ciprofloxacin therapy. AB - Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and other gastrointestinal symptoms; skin and musculoskeletal side effects may also occur. No bleeding abnormalities or alteration in coagulation have been documented. We report a case where ciprofloxacin appeared to contribute to an idiosyncratic prolongation of bleeding time although a rechallenge 8 months later did not reproduce the effect. Moreover, subsequent investigation of the influence of ciprofloxacin on bleeding parameters in 10 healthy volunteers demonstrated no alterations in bleeding parameters. PMID- 7775613 TI - Shelf-life determination of prostaglandin E1 injections. AB - A rapid stability indicating assay for the determination of prostaglandin E1 (PGE1) in pharmaceuticals was developed using High Pressure Liquid Chromatography (HPLC). A solution of 20 micrograms/ml PGE1 in 4% alcohol and 0.9% saline has an activation energy of 18,683 cal/mol and the predicted shelf-lives were: at 4 degrees C t95 = 51.8 days and t90 = 106.5 days and at 25 degrees C t95 = 4.8 days and t90 = 9.8 days. PMID- 7775615 TI - Teicoplanin or vancomycin in the treatment of gram-positive infections? AB - The glycopeptide antibiotics vancomycin and teicoplanin have similar mechanisms of action on bacterial cell wall synthesis. Their spectra of activity are limited to Gram-positive bacteria, with the degree of bactericidal activity depending on the species of micro-organism. Staphylococcus aureus, Staphylococcus epidermis, enterococci and Clostridium difficile are generally sensitive, including methicillin-resistant strains of S. aureus and S. epidermidis. Glycopeptide resistance has recently emerged in staphylococci and enterococci. Vancomycin has a shorter half-life than teicoplanin and requires multiple dosing to maintain adequate serum levels. It can only be given by prolonged intravenous infusion over 1 h. In contrast, the pharmacokinetics of teicoplanin allow for once-daily dosing, either by rapid intravenous infusion or by the intramuscular route. The latter offers reliable absorption for patients with limited venous access and is also of benefit for out-patient therapy. Teicoplanin is a safer drug than vancomycin. It is associated with a lower incidence of nephrotoxicity or ototoxicity. Compared to vancomycin, the availability of the intramuscular route and the absence of a requirement for routine serum monitoring, together with the reduced need to treat drug-related side-effects make teicoplanin more cost effective. It is as effective as vancomycin for most indications, is safe, easy to administer and an important agent for treating Gram-positive infections. Its role in hospitals is likely to increase if the price of drug acquisition is kept low. PMID- 7775617 TI - Clinical review 70: Approaches to the prevention of breast cancer. AB - In the face of an apparently increasing incidence of postmenopausal breast cancer, and with frustratingly limited gains in treatment, significant possibilities for widespread prevention of breast cancer must be vigorously explored. However, progress with this approach has been painfully slow, and the multifactorial etiology of breast cancer development is most responsible for this delay. The challenges in our approaches are to recognize the major differences between treatment and prevention and to demand a comprehensive biological rationale, an absence of serious toxic effects and likely long-term acceptability to women of interventions coming to definitive clinical trial. PMID- 7775616 TI - Immunocytochemical analyses of dehydroepiandrosterone sulfotransferase in cultured human fetal adrenal cells. AB - Dehydroepiandrosterone sulfate is the major steroid secretory product of the human fetal adrenal gland. Several factors have been shown to modulate the secretion of this steroid by cultured fetal adrenal cells. In addition to the cytochrome P450 enzymes that are important in steroid biosynthesis, dehydroepiandrosterone sulfotransferase (DST) is likely to be a key regulated enzyme in the formation of sulfated steroids, which are characteristic of the human adrenal cortex, particularly that of the fetus and the adult zona reticularis. In the present investigation, we sought to evaluate the cellular localization of DST in cultures derived from the fetal zone, neocortex, and adrenal capsule and to determine the effects of ACTH and other agonists of the protein kinase-A pathway on the abundance of DST in such cells. Cells derived from the fetal zone, neocortex, and adrenal capsule were either precultured for 3 13 days in plastic flasks followed by culture on coverslips or were cultured directly on coverslips in control medium (McCoy's 5A medium that contained 5% fetal bovine serum) or control medium plus ACTH, forskolin, or dibutyryl cAMP for 1-4 days. Cells were fixed in buffered formalin and then immunostained for DST by use of a rabbit polyclonal antiserum prepared against human liver DST. DST immunoreactivity was abundant in freshly isolated cortical cells derived from fetal zone and neocortex. DST immunoreactivity was still observable in fetal zone and neocortex cells as well as in cells prepared from enzymatic digests of adrenal capsule after scraping off adherent neocortex cells following culture for 9-14 days in control medium. Adrenal fibroblasts were negative for DST. DST abundance in cortical cells was increased in cultures supplemented with ACTH, forskolin, or dibutyryl cAMP compared to that in cultures grown in control medium alone. The results of Western blot analyses of DST in these cells were consistent with the immunocytochemical data. These results suggest that DST is present in both fetal zone and neocortex cells of the human fetal adrenal at midgestation and that the production of DST is stimulated by ACTH and agonists of the protein kinase-A signal transduction pathway in the human fetal adrenal gland. PMID- 7775618 TI - Body composition and skeletal density--mechanical loading or something more? PMID- 7775619 TI - Regular exercise dissociates fat mass and bone density in premenopausal women. AB - Body weight is one of the principal determinants of bone density and fracture frequency, but there is significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight to this relationship. As previous studies have not considered the possible role of exercise in soft tissue-bone density interrelationships, we measured areal bone mineral density (BMD), fat mass, and lean mass in eumenorrheic premenopausal women and determined whether the interrelationships of these variables are influenced by the subject's exercise status. Subjects with mean activity levels of more than 140 kilojoules/kg.day (equivalent to undertaking vigorous physical activity for > 1.5 h/week) were classified as exercisers. In the nonexercising subjects (n = 36; age, 36 +/- 8 yr), BMD was markedly weight dependent (0.45 < r < 0.62), and this was contributed to by both fat and lean tissue. Because this finding may have arisen from the mutual dependence of soft tissue mass and areal BMD on body size, fat and lean masses were reexpressed as a percentage of body weight. The percent fat tended to be positively related to areal BMD (0.23 < r < 0.35), whereas the percent lean was inversely related to this index. A second way of obviating the mutual dependence of soft tissue mass and areal BMD on body size is to derive BMD/height as an index of volumetric bone density. This parameter was only related to lean mass in the femur, whereas the correlations with fat mass were little changed. The percent fat was positively (0.29 < r < 0.43) and the percent lean was negatively (-0.43 < r < -0.29) related to BMD/height throughout the skeleton, including the femur. In the exercising subjects (n = 63; age, 33 +/- 8 yr), fat mass and lean mass were unrelated to BMD/height (r < 0.23). However, the percent lean was positively correlated with BMD and BMD/height in the femoral neck (r = 0.28 and r = 0.31, respectively). It is concluded that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, possibly through the effects of weight-bearing exercise on both of these variables. PMID- 7775620 TI - Clinical case seminar: Hypokalemia in a 52-year-old woman with non-small cell lung cancer. PMID- 7775621 TI - Extrasellar, intracavernous sinus adrenocorticotropin-releasing adenoma causing Cushing's disease. AB - This report describes a patient with pituitary-dependent Cushing's disease who had a preoperative ACTH gradient to the left at the level of the cavernous sinus. Intraoperatively, an adenoma was found entirely within the left cavernous sinus, with no direct connection to the pituitary gland. To our knowledge, such a tumor has not been reported previously. This case has implications for the diagnosis, treatment, and follow-up of patients with pituitary-dependent Cushing's disease. The presence of an entirely extrasellar ACTH-releasing adenoma in the cavernous sinus could explain why pituitary-dependent Cushing's disease may persist postoperatively, even after total hypophysectomy. The diagnosis of an intracavernous tumor can be established by cavernous sinus venography. An extrasellar intracavernous adenoma can be diagnosed intraoperatively after careful negative exploration of the sellar contents followed by incision of the cavernous sinus on the side of the ACTH gradient established by venous sampling. PMID- 7775622 TI - Glucose modulation of insulin and glucagon secretion is altered in impaired glucose tolerance. AB - Insulin and glucagon secretion was compared in women with impaired glucose tolerance (IGT; n = 19, age 58.4 +/- 0.3 yr; mean +/- SD) and women with normal glucose tolerance (NGT; n = 40, age 58.4 +/- 0.3 yr). Fasting plasma insulin levels were higher in IGT than in NGT (P = 0.026), whereas fasting glucose and glucagon levels were not different. Arginine was injected intravenously (5 g), which rapidly stimulated insulin and glucagon secretion in all subjects. Raising the blood glucose (BG) to 14 and 28 mmol/L potentiated insulin secretion and inhibited glucagon secretion. The acute insulin response to arginine (AIR = 2-5 min postload increase) at BG 14 mmol/L, but not at fasting BG or BG 28 mmol/L, was lower in IGT than in NGT (P = 0.033), as was the glucose potentiation of AIR (slopeAIR) (P = 0.020). The acute glucagon response (AGR) was higher in IGT than in NGT at BG 14 mmol/L (P = 0.016). SlopeAGR (glucose inhibition of AGR) was reduced in IGT (P = 0.001). In NGT, there was a significant inverse correlation between slopeAIR and slopeAGR (P = 0.002) not seen in IGT. We conclude that in IGT with normal fasting BG, the glucose modulation of islet function is impaired, indicating that islet dysfunction is an early lesion during the development of noninsulin-dependent diabetes mellitus. PMID- 7775623 TI - A comparison of the effects of oral and transdermal estrogen replacement on insulin sensitivity in postmenopausal women. AB - Previous studies have shown that oral, but not transdermal, administration of estrogen stimulates GH secretion in postmenopausal women. Because GH impairs insulin action, the impact of estrogen replacement therapy on carbohydrate metabolism may be influenced by the route of administration. The aim of this study was to prospectively compare the effects of oral and transdermal estrogen replacement on glucose tolerance and insulin sensitivity in postmenopausal women. In an open label, randomized, cross-over study, nine postmenopausal women were randomized to transdermal estrogen patches (Estraderm-TTS 100) or oral conjugated estrogen (Premarin, 1.25 mg) daily for 12 weeks and then crossed over to receive the alternative treatment for a further 12 weeks. An oral glucose tolerance test and hyperinsulinemic euglycemic clamp (HEC) were performed before treatment and at the end of 10 weeks of treatment. Oral and transdermal estrogen both significantly reduced LH to the same degree. Mean GH did not significantly change with transdermal estrogen, but rose significantly during oral estrogen therapy. Peak and mean glucose and insulin levels during the oral glucose tolerance test were not altered by estrogen therapy and were not significantly different between treatments. Mean glucose and insulin levels were maintained at an identical level during the HEC performed at pretreatment and during estrogen therapy. The mean glucose infusion rate required to maintain euglycemia during the HEC (mean +/- SEM, pretreatment, 40.4 +/- 4.8 mumol/kg.min) was unaltered by oral (39.8 +/- 4.6 mumol/kg.min) or transdermal estrogen treatment (42.1 +/- 4.2 mumol/kg.min). However, during the transdermal estrogen phase (60 +/- 10 mumol/L), the mean nonesterified free fatty acid concentration was suppressed to a significantly lower level during the HEC than during the oral estrogen phase (120 +/- 20 mumol/L; P < 0.05). We conclude that compared to the oral route, transdermal estrogen therapy is associated with a slight, but significant, improvement of insulin action on lipid metabolism. However, in the short term, the route of estrogen replacement therapy does not have a major impact on glucose metabolism in postmenopausal women. PMID- 7775624 TI - Somatostatin enhances insulin-stimulated glucose uptake in the perfused human forearm. AB - Somatostatin is widely used in experimental metabolic studies to control hormone actions. It has also been suggested that, in addition to its well known suppressive effects, somatostatin per se may increase insulin sensitivity. In order to examine this suggestion, we gave six healthy male volunteers (age 33 +/- 1 yr, mean +/- SEM; body mass index, 24.1 +/- 0.6 kg/m2) either a local intraarterial (brachial artery) or a systemic venous infusion of 25 micrograms/h somatostatin twice. The study consisted of a 1-h basal period and a 2-h systemic hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. Compared with the systemic control infusion, local forearm perfusion with somatostatin caused a 55% increase in insulin-stimulated forearm glucose uptake (0.74 +/- 0.18 vs. 0.47 +/- 0.19 mmol/L, P < 0.05). Intraarterial somatostatin perfusion did not alter basal forearm glucose uptake (0.14 +/- 0.07 vs. 0.17 +/- 0.12 mmol/L), the amount of glucose administered during the clamp (M-value, 3.2 +/- 0.5 vs. 3.0 +/- 0.6 mg/kg.min), or the levels of insulin, C-peptide, glucagon, or GH. Intermediary metabolite exchange across the forearm, total forearm blood flow, and oxygen saturations also remained stable. Glucose concentrations were slightly higher (0.06 +/- 0.01 mmol/L) in arterial than in arterialized blood, whereas lactate concentrations were comparatively decreased (108 +/- 51 mumol/L) in arterial blood. Our data suggest that somatostatin increases insulin-stimulated muscle utilization of glucose through local mechanisms. Although the nature of this increase remains to be established, it should be taken into consideration in metabolic studies using somatostatin. PMID- 7775625 TI - Relationships of plasminogen activator inhibitor activity and lipoprotein(a) with insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin in myocardial infarction patients and healthy controls. AB - The relationships between plasminogen activator inhibitor (PAi) activity and lipoprotein(a) [Lp(a)] and insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin (TEBG) were assessed in 42 myocardial infarction male patients and 74 healthy controls. Patients had higher levels of insulin than did controls (87 +/- 30 vs. 75 +/- 28 pmol/L, respectively; P < 0.04), and no differences were found in levels of PAi activity, testosterone, 17 beta estradiol, and TEBG. Lp(a) levels greater than 0.3 g/L were more frequent in patients than in controls (P < 0.002). In all subjects, PAi activity levels were significantly and positively correlated with body mass index (r = 0.20, P < 0.05), triglycerides (r = 0.38, P < 0.0001), and insulin (r = 0.27, P < 0.005) and were negatively correlated with testosterone (r = -0.28, P < 0.005) and TEBG (r = -0.42, P < 0.001). Stepwise multiple regression analysis showed triglyceride, insulin, and TEBG levels to be significantly related to PAi activity. No significant correlations were found between Lp(a) levels and all hormonal variables studied and between Lp(a) and PAi activity (r = -0.06, P < 0.58). These results suggest that TEBG is significantly and independently related to PAi levels. PMID- 7775626 TI - Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock. AB - In view of the immunosuppressive action of glucocorticoids (GCs), the activation of the hypothalamo-pituitary-adrenal axis in patients with sepsis or septic shock is paradoxical. At the same time, administration of GCs to these patients is not clearly beneficial. We investigated the role of GCs in severe illness by measuring the sensitivity of peripheral blood mononuclear leukocytes to GCs in a mitogen-stimulated lymphocyte proliferation assay. In addition, we studied the role of interleukin-2 and several other cytokines in this system. Cells from patients with sepsis or septic shock (n = 15) were more sensitive to the antiproliferative action of GCs than were cells from normal controls (IC50 6.7 +/ 2.1 nmol/L for patients vs. 19.5 +/- 2.5 nmol/L for controls; P < 0.01). This increased sensitivity of the peripheral mononuclear cells to dexamethasone during the period of sepsis normalized during the ensuing period of clinical recovery of these patients. Dexamethasone inhibited the production of interleukin-2 in the mitogen-stimulated cells. Addition of interleukin-2 antagonized the suppressive effects of dexamethasone in a dose-dependent manner, both in cells from controls and in cells from patients with sepsis. To a lesser extent, the combination of interleukin-1, interleukin-6, and tumor necrosis factor-alpha also counteracted the effects of dexamethasone. In conclusion, our results suggest that not only the activity of the hypothalamo-pituitary-adrenal axis but also the sensitivity to GCs is regulated during sepsis and septic shock. Generally there is an increased sensitivity to GCs, which might help to protect the organism as a whole through supportive effects on metabolism and vasculature. This hypersensitivity is counteracted, possibly at the site of inflammation, by high local concentrations of cytokines. This would enable an adequate local response of the immune system in the presence of elevated cortisol levels. In view of the increased sensitivity of peripheral leukocytes to GCs, treatment of these patients with high doses of GCs may not be beneficial or may even be harmful. PMID- 7775627 TI - Glucocorticoids, sympathetic activity, and presynaptic alpha 2-adrenoceptor function in humans. AB - The sympathetic nervous system and the pituitary-adrenocortical system are two of the body's main stress effector systems. Animal studies have indicated that exogenously administered glucocorticoids inhibit sympathetic outflows and interfere with the function of presynaptic alpha 2-adrenoceptors modulating neuronal norepinephrine (NE) release. The present study tested whether glucocorticoids produce similar effects in humans. In a randomized, double-blind, placebo-controlled cross-over experiment, 15 healthy subjects took 20 mg prednisone or placebo orally daily each morning for 1 week, followed by the other drug after a 1-week washout. On the last day of each treatment week, blood samples were drawn for assays of plasma levels of catechols and ACTH before and after iv infusion of the alpha 2-adrenoceptor antagonist yohimbine (YOH) (0.125 mg/kg bolus, 0.001 mg.kg-1.min-1 infusion). In 7 subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity (MSNA) was also measured at baseline and after YOH infusion at the end of both treatment weeks. Prednisone decreased plasma NE levels and MSNA compared with levels after placebo (1.09 +/- 0.11 nmol/L vs. 1.40 +/- 0.13 nmol/L, P < 0.01; 30 +/- 4 bursts/min vs. 36 +/- 3 bursts/min, P < 0.05) without affecting blood pressure or pulse rate. YOH increased mean arterial blood pressure by 12% (P < 0.001) and heart rate by 7% (P < 0.05); prednisone did not alter these effects of YOH. YOH-induced proportionate increments in plasma NE levels averaged about 10 times those in MSNA. Prednisone did not affect the YOH-induced proportionate increments in plasma NE levels (placebo, 243%; prednisone, 237%) or MSNA (placebo, 22%; prednisone, 23%). The decrements in MSNA and plasma NE levels after prednisone treatment indicate that glucocorticoids inhibit sympathoneural outflows in humans. The 10-fold larger NE than MSNA response to YOH confirms substantial inhibitory modulation of NE release by alpha 2-adrenoceptors on noradrenergic terminals, and the similarity of responses to YOH after prednisone or placebo suggests that glucocorticoid induced sympathoinhibition occurs independently of altered modulatory function of alpha 2-adrenoceptors on noradrenergic terminals. PMID- 7775628 TI - Stimulation of intracellular calcium concentration by adenosine triphosphate and uridine 5'-triphosphate in human term placental cells: evidence for purinergic receptors. AB - Recent data suggest an important role for calcium (Ca2+) in human placental endocrinology. Thus, the regulation of Ca2+ influx seems to be implicated in the modulation of human placental lactogen and hCG release. A possible mechanism of influx regulation is through receptor-operated channels. One of the most characterized receptor gating Ca2+ channels, the ATP receptor, stimulates the intracellular calcium concentration ([Ca2+]i) in various tissues. The aim of this study was to determine whether ATP receptors gating Ca2+ channels are also present in placental cells. We thus determined the effect of ATP on [Ca2+]i in human term trophoblastic cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. ATP stimulated a 4.3 +/- 0.4 (+/- SE)-fold increase in [Ca2+]i, with a half-maximal effective concentration (EC50) of 1.5 mumol/L. The pharmacological activation profile suggests the presence of purinergic P2u receptors (nucleotide receptors), because uridine 5'-triphosphate (UTP) also stimulated [Ca2+]i (4.0 fold increase, with an EC50 of 10 mumol/L). The ATP-stimulated [Ca2+]i was partly sensitive to pertussis toxin; we observed a 58% inhibition of ATP-induced [Ca2+]i with the toxin without effect on basal [Ca2+]i. The ATP- and UTP-stimulated [Ca2+]i declined with time in the presence of ATP (or UTP). The rate of deactivation was rapid (t1/2, < 60 s with 10(-5) mol/L ATP) and concentration dependent. The deactivation occurring during one application of ATP or UTP resulted in a diminution of subsequent responses. The recovery was incomplete even with long waiting times (up to 30 min). ATP and UTP also stimulated inositol phosphate production with EC50 values of 11 and 15 mumol/L, respectively, but not human placental lactogen or hCG release in experiments in which known secretagogues were effective. The results suggest the presence in human term placental cells of P2u receptors pharmacologically similar to those observed in other tissues, especially in the pituitary and amnion. The physiological significance of this stimulation of [Ca2+]i by ATP and UTP in the human placenta remains to be investigated. PMID- 7775629 TI - Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. AB - Combined hormonal oral contraceptives (OCs) may lead to a mild rise in blood pressure and body weight. In rare instances, large increments in blood pressure are measured. We investigated the effect of a combination of ethinyl estradiol (EE) plus a progestogen with antimineralocorticoid, i.e. natriuretic, properties [Drospirenone (DRSP)] on body weight, blood pressure, the renin-aldosterone system, atrial natriuretic factor, plasma lipids, and glucose tolerance. It is anticipated that this will lead to the development of an OC that does not raise body weight or blood pressure. Four groups of 20 women each received 30 micrograms EE plus 3 mg DRSP (group A), 20 micrograms EE plus 3 mg DRSP (group B), 15 micrograms EE plus 3 mg DRSP (group C), and, as a control OC, 30 micrograms EE plus 150 micrograms levonorgestrel (Microgynon, Schering; group D) for 6 months. During the OC-free control cycles before and after treatment and throughout treatment, the target parameters were measured. Between the pretreatment cycle and the sixth treatment cycle, mean body weight fell by 0.8 to 1.7 kg in groups A, B, and C (P < 0.05 vs. D), whereas it rose by 0.7 kg in group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in groups A, B, and C (significant for A and C vs. D) and increased by 1-2 mm Hg in group D. Renin substrate rose equally in all groups (P < 0.05), whereas PRA and plasma aldosterone rose significantly only in the DRSP groups, presumably due to sodium loss. In the DRSP groups, high density lipoprotein cholesterol rose (P < 0.05), in contrast to group D. Low density lipoprotein cholesterol fell slightly (P > 0.05), whereas triglyceride levels showed a stronger increase in the DRSP groups (P < 0.05) than in group D. All groups attained good cycle control; group A had the best. Side-effects were minimal. To our knowledge, this is the first report on a combined OC that leads to a small decrease in body weight and blood pressure. It may be especially beneficial for women susceptible for a gain in weight and a rise in blood pressure. PMID- 7775630 TI - 17 beta-estradiol stimulates prostacyclin, but not endothelin-1, production in human vascular endothelial cells. AB - The exact mechanisms by which estrogens protect against occlusive vascular disorders are not known. One possibility could be an effect on vascular endothelial vasoactive compounds, such as vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin (ET-1). Here we report on the effect of 17 beta estradiol on the synthesis of PGI2 and ET-1 in cultured human umbilical vein endothelial cells. These cells were incubated in the absence (control) and presence of 17 beta-estradiol (0.001-1 mumol/L) for 3-24 h with serum (10%) or without serum. The release of PGI2, as assessed by its metabolite 6-keto prostaglandin F1 alpha, and that of ET-1, were assessed by RIA. 17 beta-Estradiol (0.01-0.1 mumol/L) predissolved in ethanol (final concentration, 0.01%) increased PGI2 production by 26-30% in endothelial cells incubated without serum. This increase in PGI2 production was enhanced up to 66% when 17 beta-estradiol (1 mumol/L) was encapsulated within beta-cyclodextrin. The stimulation of PGI2 production was detectable after 12 h of incubation. The 17 beta-estradiol-induced stimulation of PGI2 production was blocked in dose-dependent manner by antiestrogenic tamoxifen. 17 beta-Estradiol failed to affect the production of PGI2 if the endothelial cells were incubated with serum and had no effect on ET-1 production under any conditions. 17 beta-Estradiol-induced stimulation of vasodilatory and antiaggregatory PGI2 production without a concomitant change in vasoconstrictory ET-1 production may provide one explanation for the ability of estradiol to maintain vascular health and protect against vascular disorders. PMID- 7775632 TI - Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. AB - Vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and VEGF peptide were studied in human myometrium and leiomyomata. Amplification of complementary DNA from myometrium and leiomyomata by the polymerase chain reaction revealed three species of mRNA encoding VEGF: VEGF189, VEGF165, and VEGF121. In situ hybridization demonstrated VEGF mRNA expression throughout the smooth muscle cells of myometrium and leiomyomata. VEGF-like immunoreactivity was also detected in these tissues by immunocytochemistry. Quantification of VEGF mRNA using an RNAse protection assay demonstrated that in normal myometrium, levels of VEGF mRNA are significantly higher in the secretory phase than in the proliferative phase of the cycle. Leiomyomata did not have significantly different levels of VEGF mRNA compared with normal myometrium. In untreated leiomyomata, there was no significant difference between VEGF mRNA levels in the proliferative and secretory phases of the cycle. Leiomyomata from women treated with a GnRH anlog did not have significantly different levels of VEGF mRNA from untreated leiomyomata. PMID- 7775631 TI - Molecular and pharmacological characterization of somatostatin receptor subtypes in adrenal, extraadrenal, and malignant pheochromocytomas. AB - SRIH receptors were quantified by radioautography in 33 pheochromocytomas and 5 normal adrenals. Binding was evenly distributed over the tumors, whereas it was more intense in adrenal medulla than cortex. Binding levels were significantly higher in tumoral than in normal tissue, but did not differ among tumors. At 100 nmol/L, SRIH-14 and octreotide (or BIM23014 in cross-linking experiments to a 57 kilodalton component) comparably displaced SRIH binding, BIM23042 and BIM23052 were less potent, and BIM23056 was inefficient. In increasing doses, the rank order of potency was SRIH-14 > SRIH-28 > octreotide > BIM23052 >> BIM23042 >> > BIM23056. All five species of SRIH receptor (SSTR1-5) messenger ribonucleic acids (mRNAs) were measurable in pheochromocytomas and normal adrenals, SSTR2 and SSTR4 mRNA were the most expressed moieties. The proportion of SSTR5 mRNA species was higher in normal adrenals (21%) than in pheochromocytomas (6%). In the presence of guanylylimidodiphosphate, SRIH binding was reduced by 83%. However, SRIH did not alter basal or forskolin-stimulated adenylyl cyclase activity. Taken together, these pharmacological and molecular data indicate that SRIH binding on pheochromocytomas depends on a mixed population of receptors, mainly of the SSTR2 and SSTR4 subtypes, efficiently coupled to G proteins, but not to adenylyl cyclase inhibition. PMID- 7775634 TI - Degree of activation of the pituitary-testicular axis in early pubertal boys with constitutional delay of growth and puberty determines the growth response to treatment with testosterone or oxandrolone. AB - Early pubertal boys (testicular volume, 4-6 mL) with constitutionally delayed growth and puberty were randomized to 3 months of treatment after a baseline 12-h overnight hormone profile: group 1 (n = 5), daily placebo; group 2 (n = 5), 2.5 mg oxandrolone daily; or group 3 (n = 6), 50-mg testosterone monthly im injections. LH and GH profiles (15-min samples) were analyzed by peak detection (Pulsar), Fourier transformation, and autocorrelation. FSH and testosterone levels were measured hourly, and insulin, sex hormone-binding globulin, insulin like growth factor-I, and insulin-like growth factor-binding protein-3 levels were determined at 0800 h. Multiple regression was used to analyze the response to treatment (growth) with respect to baseline features. Endocrine variability was marked. Profiles ranged from unreactive to well established LH pulsatility and adult testosterone levels. The areas under the curve (AUC) for LH, FSH, and testosterone ranged 10-fold (4.4-46.3 IU/L.h), 8-fold (7.9-63.4 IU/L.h), and 45 fold (3.6-161.7 nmol/L.h), respectively. The growth response was individually varied, but significantly increased 0-6 months in the active treatment groups. Age, testicular volume, and LH AUC interacted significantly (r2 = 0.95; P < 0.05). Allowance for these produced a highly significant treatment effect (P = 0.006). Age, testicular volume, LH AUC, and testosterone AUC, but not treatment, significantly increased growth by 0-12 months (r2 = 0.88; P < 0.05). We demonstrate a spectrum of activation of the reproductive axis despite tight clinical staging. This, and not GH status at treatment commencement, influenced the growth response. PMID- 7775633 TI - Antiovulatory actions of RU 486: the pituitary is not the primary site of action in vivo. AB - Continuous administration of RU 486 impairs follicular development and inhibits ovulation in women. Yet, the mechanism of ovulation inhibition remains unknown. To characterize the mechanism(s) of ovulation inhibition, we studied six regularly menstruating cynomolgus monkeys for three consecutive (control-rest treatment) cycles. Monkeys received 1 mg/kg.day RU 486 in between cycle days 2 22. Basal and GnRH-stimulated (1 and 50 micrograms GnRH, iv, 2 h apart) secretion of LH and FSH was assessed using serial blood samples (every 15 min for 12 h) collected on cycle day 10. Serum levels of estradiol (E2), progesterone (P4), RU 486, cortisol, LH, FSH, and PRL were analyzed by RIAs, the bioactivity of LH was assessed using a mouse Leydig cell assay. The mean cycle length was prolonged by RU 486 treatment from 31.8 to 69.8 days (P = 0.008). During RU 486 treatment, patterns of E2 secretion varied considerably; the mean +/- SD E2 level was 204 +/ 139 pmol/L. LH peaks and P4 profiles compatible with luteal function were seen only before resumption of menstruation. However, one monkey had an increase in P4 after the GnRH challenge-induced LH secretion. Basal levels of LH varied between suppressed and apparently normal values, whereas basal FSH seemed little affected by RU 486 treatment. In two monkeys with E2 secretion indicative of normal follicular development, minor peaks of LH, but no rises in serum P4, were seen. The ratio of bioactive/immunoactive LH was reduced in these monkeys during RU 486 treatment compared to that during the washout period of the treatment cycle. Surprisingly, the pituitary responsiveness to acute GnRH challenge was not affected by RU 486 administration. The individual levels of RU 486 were similar during the treatment period (mean, 40 nmol/L). A resumption of ovulatory cycles occurred when RU 486 concentrations were below 2.5 nmol/L. We conclude that in cynomolgus monkeys, inhibition of ovulation by RU 486 occurs mainly at the level of the hypothalamus, with possible additional effects on the granulosa cell function and alterations of LH bioactivity. PMID- 7775635 TI - Estrogen receptor gene expression in human uterine leiomyomata. AB - Estrogen and progestin are believed to be important physiological regulators of uterine leiomyoma growth. We recently showed that progesterone receptor messenger ribonucleic acid (mRNA) and protein levels are increased in human uterine leiomyomas compared with those in myometrial biopsy tissue obtained from the same patient. To further characterize the molecular mechanisms underlying abnormal growth of uterine leiomyomas, we analyzed biopsy samples of tumor and adjacent normal myometrium for estrogen receptor (ER) gene expression. Northern analysis indicated that ER mRNA levels were increased 1.4-to 12.6-fold in leiomyoma compared with myometrium in all patients examined (n = 11), whereas beta-actin mRNA was not different between the two groups. The size of the primary ER mRNA transcript was 6.2 kilobases in both leiomyoma and myometrium, indicating no gross mutation of the ER gene. An ER protein of 66 kilodaltons was detected by Western blot analysis, and quantitative immunoassay of ER revealed 9448 +/- 1955 fmol/mg DNA in leiomyoma compared to 2827 +/- 979 fmol/mg DNA in myometrial tissue. Scatchard analysis of 17 beta-estradiol binding to cell-free extracts revealed enhanced binding capacity (per mg DNA) in leiomyoma tissue (n = 6) of about 6-fold, whereas ER binding affinity was not substantially different between the leiomyoma and adjacent myometrial tissues. We propose that increased expression of progesterone receptor in leiomyoma is most likely a consequence of overexpression of functional ER that results in increased end-organ sensitivity to estradiol. PMID- 7775636 TI - Analysis of the insulin receptor gene in noninsulin-dependent diabetes mellitus by denaturing gradient gel blots: a clinical research center study. AB - We have used a new technique of denaturing gradient gel blotting to determine the prevalence of alterations in the intracellular domain of the insulin receptor in normal individuals and subjects with non-insulin-dependent diabetes mellitus (NIDDM). This method detects DNA sequence differences as restriction fragment melting polymorphisms (RFMP) and is sensitive to changes in sequence at both restriction sites and within the fragments themselves. Using restriction digests with AluI, HaeIII, HinfI, RsaI, Sau3A, and Sau96, 12 RFMPs were found to localize to the region of the beta-subunit of the insulin receptor gene. Using exon specific probes, these RFMPs could be localized to specific regions surrounding individual exons, including exons 14, 15, 17, 19, 20, and 22. In general, linkage disequilibrium between polymorphisms was inversely related to their distance in the gene structure, although there was a "hot spot" for recombination between exons 19 and 20. No difference in melting temperatures or allele frequency was observed between NIDDM patients and controls. These data indicate that the region of the insulin receptor gene coding for the intracellular portion of the beta subunit is highly polymorphic and that polymorphisms surrounding specific exons can be identified by denaturing gradient gel blotting, but there is no evidence that variation at this locus contributes to NIDDM susceptibility in most individuals. PMID- 7775637 TI - Trophoblast and placental villous core production of lipid peroxides, thromboxane, and prostacyclin in preeclampsia. AB - Placentas obtained from women with preeclampsia produce more lipid peroxides and more thromboxane, but less prostacyclin, than normal. The tissue compartments within the placenta that are responsible for this are not known. The placenta is a heterogeneous tissue compartmentalized into trophoblast cells and villous core tissue that is comprised of stromal and vascular tissue. In this study we determined the placental compartments responsible for increased production of lipid peroxides and thromboxane in preeclampsia. Placentas were obtained from six normally pregnant women and seven women with preeclampsia. Trophoblast cells and villous core tissues were isolated and incubated in Dulbecco's Modified Eagle's Medium for 48 h. Samples were collected at 0, 2, 6, 16, 28, and 48 h of incubation and analyzed spectrophotometrically for lipid peroxides by a peroxide equivalent assay and for thromboxane and prostacyclin by RIA of their stable metabolites, thromboxane-B2 and 6-keto-prostaglandin-F1 alpha. Trophoblast cells isolated from preeclamptic placentas produced significantly more lipid peroxides (1972 +/- 502 vs. 1102 +/- 335 pmol/micrograms protein after 48 h of incubation), more thromboxane (328 +/- 57 vs. 153 +/- 53 pg/microgram at 48 h), and more prostacyclin (50 +/- 11 vs. 13 +/- 3 pg/microgram at 48 h, respectively) than trophoblast cells isolated from normal placentas. Villous core tissue isolated from preeclamptic placentas produced significantly more lipid peroxides (455 +/- 107 vs. 241 +/- 34 pmol/microgram) and more thromboxane (148 +/- 51 vs. 76 +/- 14 pg/microgram) than normal villous core tissue, but there was no difference in prostacyclin production (36 +/- 11 vs. 40 +/- 9 pg/microgram). Because of the increase in thromboxane production, the ratio of thromboxane to prostacyclin was higher in preeclamptic than normal villous core tissue (6.29 vs. 2.17). Comparison of production by different compartments within the placenta demonstrated that lipid peroxides and thromboxane were primarily produced by the trophoblast cells and stromal tissue, whereas prostacyclin was primarily produced by the vascular tissue. We conclude that increased placental production of lipid peroxides and thromboxane in preeclampsia originates from both the trophoblast cell and the villous core compartments. As the placenta secretes lipid peroxides, the trophoblast cells could be a source of increased lipid peroxides in the maternal circulation of women with preeclampsia. The increased ratio of thromboxane to prostacyclin in the villous core could be responsible for increased placental vasoconstriction. PMID- 7775638 TI - Insulin-mediated increase in blood flow is impaired in the elderly. AB - It has recently been recognized that the ability of insulin to augment blood flow is reduced in insulin-resistant conditions such as obesity and noninsulin dependent diabetes mellitus. Normal aging is characterized by resistance to insulin-mediated glucose uptake. We undertook the following studies with the hypothesis that the resistance to insulin-mediated glucose uptake that occurs with aging is caused in part by a reduction in insulin-mediated blood flow. These experiments were conducted on healthy young (n = 13; age, 24 +/- 1 yr; body mass index: 22.2 +/- 0.6 kg/m2) and old (n = 13; age, 77 +/- 1 yr; body mass index: 24.2 +/- 0.5 kg/m2) subjects. Each subject underwent two studies. In the control study, saline was infused for 4 h. In the euglycemic clamp study, insulin was infused for 4 h at a rate of 40 mU/m2.min in the young subjects and 34 mU/m2.min in the old subjects. Blood samples were taken, and calf blood flow was measured using venous occlusion plethysmography at regular intervals in each study. Basal calf blood flow was lower in the elderly (young subjects: 1.51 +/- .08 mL/100 mL tissue per min; old subjects: 1.15 +/- 0.07 mL/100 mL tissue per min, P < 0.002). During the euglycemic clamp studies, steady-state insulin and glucose values were similar in the two age groups. Glucose disposal rates were significantly higher in the young subjects (P = 0.01 by analysis of variance). Mean arterial pressure values were significantly higher in the elderly (P < 0.001 by analysis of variance) throughout the clamp, but there was no significant change over time in either age group. The mean incremental blood flow rate at steady-state (180-240 min) was significantly higher in the young subjects (0.76 +/- 0.23 mL/100 mL tissue per min) than in the old subjects (0.05 +/- 0.09 mL/100 mL tissue per min, P < 0.01). There was a significant correlation between steady-state glucose disposal rate values and incremental blood flow rates in the young subjects (r = 0.59, P < 0.05) but not in the old subjects (r = 0.21, P = NS). We conclude that normal aging is characterized by an impairment in the ability of insulin to modulate blood flow, which may contribute in part to the insulin resistance of aging. PMID- 7775639 TI - Human T-lymphotropic virus type I-associated uveitis in patients with Graves' disease treated with methylmercaptoimidazole. AB - Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU. PMID- 7775640 TI - Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium. AB - Implantation is the process by which the blastocyst becomes intimately connected with the maternal endometrium/decidua. The independently developing preimplantation blastocyst then becomes dependent on the maternal environment for its continued development. Although the factors involved in the regulation of blastocyst implantation are incompletely understood, recent studies strongly suggest a critical role for leukemia inhibitory factor (LIF) in mice. We showed previously that LIF acts on human trophoblasts to shift their differentiation toward the anchoring phenotype by increasing the synthesis of fibronectin. In the present study, we first evaluated the temporal expression of LIF in the human endometrium in order to gain further insights into the role of LIF in human implantation. We established the LIF is expressed in the endometrium in a menstrual cycle-dependent manner. The most abundant LIF messenger ribonucleic acid (mRNA) levels are observed in the mid- and late-luteal phase samples. LIF mRNA was also present in decidual tissues of first trimester of pregnancy, but levels were lower than those found in the midluteal endometrium. We then investigated the regulation of LIF expression in human endometrial cells in culture by cytokines, steroid hormones, and growth factors. We could not show any direct stimulatory evidence of steroid hormones (estradiol and progestins) on LIF mRNA expression or protein production by endometrial cells in culture. On the other hand, we showed that interleukin-1, tumor necrosis factor-alpha, platelet derived growth factor, epidermal growth factor, and transforming growth factor beta are potent inducers of LIF expression in endometrial stromal cells in culture in a concentration- and time-dependent manner. Interferon-gamma acted to inhibit LIF expression induced by these cytokines. In contrast, we found high constitutive and relatively less regulated levels of LIF mRNA in the endometrial gland cells. The timing of the expression of LIF in the endometrium suggests a potential role in the implantation. The regulation of the expression of LIF may have an important role in the physiological and pathological processes involving human implantation. PMID- 7775641 TI - Renal mass and serum calcitriol in male idiopathic calcium renal stone formers: role of protein intake. AB - To determine whether chronic overconsumption of protein might increase renal mass and cause up-regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] production, 57 male recurrent idiopathic calcium stone formers (RCSF), 29 with hypercalciuria (HCSF; urinary calcium x V, > 7.50 mmol/day) and 28 with normocalciuria (NCSF), were compared with 15 healthy male controls (C) while consuming a free choice diet. Renal mass in RCSF was measured by the sum of the surface areas of right and left kidneys (square centimeters) on plain films of the abdomen by a computer assisted sonic stylus; in C, renal mass was assessed sonographically. Serum intact PTH and 1,25-(OH)2D were measured radioimmunometrically. In HCSF, urinary phosphate x V (35.9 +/- 1.2 mmol/day) was higher than that in NCSF (29.3 +/- 1.3 mmol/day; P = 0.0009) or C (28.7 +/- 1.8 mmol/day; P = 0.005); urinary creatinine x V (16.5 +/- 0.5 mmol/day) was also higher in HCSF than in NCSF (15.0 +/- 0.5 mmol/day; P = 0.024) or C (13.8 +/- 0.6 mmol/day; P = 0.002). For identical blood levels of ionized calcium and phosphate, the 1,25-(OH)2D/PTH concentration ratio (an index of regulation of 1,25-(OH)2D production) was higher in HCSF (6.5 +/- 1.0) than in NCSF (4.0 +/- 0.3; P = 0.005). In addition, the sum of the surface areas of right and left kidneys was increased in HCSF (163.4 +/- 2.9 cm2) compared with that in NCSF (140.5 +/- 3.1 cm2; P = 0.0001), and it positively correlated with urinary phosphate x V (r = 0.429; P = 0.001) as well as with urinary creatinine x V (r = 0.294; P = 0.026); no such correlation was noted in C. Calcitriol levels were positively related to renal mass in RCSF (r = 0.316; P = 0.018), but not in C. Finally, urinary calcium x V positively correlated with the serum calcitriol/PTH concentration ratio only in RCSF (r = 0.388; P = 0.003). These findings suggest that protein overconsumption may cause an increase in renal mass and up-regulate calcitriol production in some male RCSF, an effect that would subsequently cause "idiopathic" hypercalciuria. PMID- 7775642 TI - Urinary pyridinoline and deoxypyridinoline in healthy children and in children with growth hormone deficiency. AB - To assess the bone growth status in healthy children, urinary pyridinoline (PYR) and deoxypyridinoline (DPYR) levels, which are specific bone resorption markers, were studied in 192 healthy children, aged 3-14 yr. In healthy children ages 3-5 yr, the urinary PYR level was about 10 times higher than that in healthy adults (238.3 +/- 22.7 pmol/mumol Cr in boys and 261.8 +/- 14.2 pmol/mumol Cr in girls; mean +/- SE, and the level declined gradually with age. In boys, the urinary PYR level began to rise at about 10 yr of age and peaked 2 yr later, declining thereafter. In girls, urinary PYR level declined rapidly after 11 yr. The age related changes in urinary DPYR levels closely resembled those in urinary PYR levels. We further studied PYR and DPYR levels in 17 GH-deficient children who were beginning treatment with GH. After 2-3 months of GH therapy, 1.3-fold significant increases in urinary PYR and DPYR levels were observed. These results indicate that the bone resorption in children is increased relative to that in adults, that urinary PYR and DPYR levels are increased during puberty when the growth rate is markedly elevated, and that bone resorption in children is accelerated by GH therapy. PMID- 7775643 TI - 3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice induced pseudoaldosteronism. AB - 18 beta-Glycyrrhetinic acid (GA) has been thought to be one of the major metabolites that causes licorice-induced pseudoaldosteronism. However, we found no difference in the blood level of GA between the patients with and without pseudoaldosteronism. We measured the blood concentration of 3 beta-D (monoglucuronyl)18 beta-glycyrrhetinic acid (3MGA), another metabolite of 3 beta D-diglucuronyl-18 beta-glycyrrhetinic acid (glycyrrhizin), by high performance liquid chromatography and found an increased concentration of 3MGA in 10 patients with licorice-induced pseudoaldosteronism, but not in 11 patients without pseudoaldosteronism. To investigate whether 3MGA can inhibit 11 beta hydroxysteroid dehydrogenase, we incubated rat renal microsome with or without 3MGA and measured the conversion rate of [3H]cortisol to [3H]cortisone. 3MGA was found to be a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase, allowing cortisol to exert its full mineralocorticoid effects. These results suggest that licorice-induced pseudoaldosteronism is due to an increased concentration of 3MGA, but not GA, in the circulating blood of these patients. PMID- 7775644 TI - Inhibition of steroid 5 alpha-reductase with finasteride: sleep-related erections, potency, and libido in healthy men. AB - To objectively measure the effects of a 5 alpha-reductase inhibitor on erectile function, we studied 20 sexually active men (aged 41-64 yr) during double blind, randomized administration of 5 mg/day finasteride (F) or placebo (P). Serum testosterone and dihydrotestosterone (DHT) were measured every 4 weeks. Sleep related erections were assessed with comprehensive polysomnography for 2 nights before randomization (session 1) and at week 12 (session 2). Sexual function questionnaires were administered weekly. Serum DHT levels at week 0 were 1.47 +/- 0.11 and 1.16 +/- 0.27 nmol/L (P > 0.05) in the P and F groups, respectively. F group levels fell to 31% and 28% of control values at week 4 and 12. Penile tip peak tumescence time increased on second nights more in the P than the F group at 12 weeks, producing a session main effect (P < 0.02) and a group X session interaction (P < 0.05). No significant group X session interactions were found for any sleep erection measures in a best night analysis or for self-reported sexual activity. Thus, F did not consistently suppress sleep-related erections compared to P. F primarily inhibits type 2 5 alpha-reductase activity; however, type 1 5 alpha-reductase is the major enzyme in the central nervous system. Therefore, DHT involvement in the maintenance of libido and potency is not excluded. Nonetheless, these data support the feasibility of using a type 2 inhibitor to treat benign prostatic hyperplasia without impairing erectile function. PMID- 7775645 TI - Priming of human polymorphonuclear neutrophilic leukocytes by insulin-like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation, and oxidative burst. AB - Insulin-like growth factor I (IGF-I) is a GH-dependent peptide regulating mammalian growth that seems to be of importance for the normal development and function of the immune system. Polymorphonuclear neutrophilic leukocytes (PMNLs) are terminally differentiated phagocytes essential for host defense, and in the present study, recombinant human IGF-I was shown to be a powerful primer of mature human PMNLs. IGF-I augmented the PMNL phagocytosis of both immunoglobulin G-opsonized Staphylococcus aureus and complement-opsonized Candida albicans. In addition, the growth factor increased PMNL complement receptor expression [complement receptors 1 (CD35) and 3 (CD11b)] and primed the cells to stronger f met-leu-phe-induced degranulation of both specific and azurophilic granules [markers: CD11b, CD35 and CD67 (specific granules); CD63 (azurophilic granules)]. In contrast, IGF-I did not alter the PMNL surface expression of Fc gamma RI (CD64), Fc gamma RII (CDw32), or Fc gamma RIII (CD16). PMNLs exposed to IGF-I increased their f-met-leu-phe and phorbol myristate acetate-induced oxidative burst, as evaluated by hydrogen peroxide production, whereas IGF-I did not influence PMNL actin polymerization. The priming of PMNLs by IGF-I was dependent on time and concentration, and saturating amounts of a monoclonal antibody to the IGF-I receptor blocked the priming of PMNLs by this peptide. These experiments demonstrate that IGF-I can selectively stimulate mature PMNL functions, providing further evidence for the interaction between the immune and the endocrine systems. PMID- 7775646 TI - The human adrenal microsomal glucose-6-phosphatase system. AB - Microsomal glucose-6-phosphatase (EC 3.1.3.9) is a multicomponent enzyme system traditionally thought only to be present in gluconeogenic tissues. The enzyme is associated with transport systems, for its substrate glucose-6-phosphate, and its products phosphate and glucose. It has been shown, using immunohistochemical methods and monospecific antibodies, that the component proteins of the enzyme system are present in human embryonic and fetal adrenal gland and are predominantly located in the fetal zone with lesser reactivities in the definitive zone. In addition, specific glucose-6-phosphatase activity was shown, and the rates of entry of glucose-6-phosphate, phosphate, and glucose into microsomes isolated from human fetal adrenals were measured. Although the complete enzyme system is present, the ratio of the component activities and comparison with human fetal and adult liver indicate that the regulation of the adrenal and liver glucose-6-phosphatase systems is different. In the human postnatal adrenal, immunoreactivies to the protein components decrease dramatically and are confined predominantly to the zona reticularis, suggesting a specialized role for adrenal glucose-6-phosphatase in fetal life. PMID- 7775647 TI - Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome. AB - Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled ovarian stimulation treatment. This iatrogenic condition is potentially lethal and occurs in 0.3-5% of stimulated ovarian cycles. hCG exacerbates OHSS. The pathophysiology of OHSS is still unknown; therefore, treatment regimens are aimed at ameliorating symptoms. Prominent features of OHSS are an elevated risk of thromboembolism due to enhanced production of von Willebrand factor by endothelial cells and ascites, or pulmonary edema due to increased vascular permeability followed by third space fluid accumulation. Both of these sequelae can be evoked by vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF). High concentrations of VEGF/VPF have been demonstrated in ascitic fluid from patients with OHSS, but the source of VEGF/VPF in these patients remained unidentified. Here we report that the messenger ribonucleic acid expression of VEGF/VPF in human luteinized granulosa cells (GCs) is dose and time dependently enhanced by hCG in vitro. Furthermore, VEGF/VPF proteins are produced by GCs. Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs. PMID- 7775648 TI - Role of the serotonin receptor subtype 5-HT1D on basal and stimulated growth hormone secretion. AB - At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release. PMID- 7775649 TI - Growth hormone insensitivity syndrome due to point deletion and frame shift in the growth hormone receptor. AB - By direct amplification and sequencing of genomic DNA by the polymerase chain reaction, we have identified a unique 2-base deletion in the growth hormone receptor gene of a patient with extreme short stature and growth hormone insensitivity (Laron) syndrome. We found a deletion of bases 118-119 in exon 4, which corresponds to the extracellular domain of the growth hormone receptor. Since this mutation encodes a frameshift in the amino acid sequence and a stop codon relatively early in the translation of the growth hormone receptor, we conclude that this deletion caused the growth hormone insensitivity in this patient. PMID- 7775650 TI - [A molecular pathological study on the localization of the human papillomavirus using nested PCR and in situ hybridization methods in paraffin embedded tissues]. AB - This study was designed to use nested polymerase chain reaction (nested PCR), in situ hybridization (ISH) and immunohistochemical techniques to identify human papillomavirus (HPV) in tissues fixed in formalin and embedded in paraffin. Eighty cases including 17 cases of condyloma acuminatum, 10 cases of cervical dysplasia, 6 cases of carcinoma in situ, 16 cases of squamous cell carcinoma of the uterine cervix, 14 cases of nasal and paranasal papilloma, 1 case of transitional cell papilloma and 16 cases of esophageal squamous cell carcinoma were examined. With the nested PCR method, the positive reaction rate of HPV was higher than with the single step PCR method. The detection rate was about ten fold higher in condyloma acuminatum and two times higher in cervical dysplasia with the nested PCR method. In four cases of condyloma acuminatum, ISH was positive. Three of those cases were type 18 HPV and the another was type 11 HPV. Immunohistochemically, HPV was detected only in the cases of condyloma acuminatum. The nuclei of superficial epithelial cells, especially kilocytes reacted positively both by ISH and immunohistochemical methods. Nested PCR is not a very complicated technique, and the detection rate is higher than that of commonly used pathological techniques. These results suggest that nested PCR will be a useful test for HPV routine pathological diagnosis. PMID- 7775651 TI - [Effect of newly developed analogue of growth hormone releasing peptide [D-Ala-D beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102)] on growth hormone secretion in adult male rats]. AB - The effect of a newly developed hexapeptide; D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys NH2 (KP-102) on GH secretion was studied in adult male rats. KP-102 induced a large plasma GH response at a dose of 0.5 micrograms/kg BW in conscious rats, although GH-releasing abilities of KP-102 varied markedly depending on the phase of GH secretion. Among urethan-anesthetized rats, KP-102 alone exerted a small influence on GH secretion, but it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). The rest of studies were performed on urethan anesthetized rats. During intermittent administration of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when cysteamine HCl was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in cysteamine-administered rats. Taken together, these findings suggest that the KP-102-induced GH secretion largely depends on GRF and the secretagogue potentiates the GRF effect by antagonizing the SS action at the level of somatotropes. It is concluded that KP-102 alone or in combination with GRF provides a means of stimulating GH secretion in the face of elevated inhibitory tone mediated by SS. PMID- 7775652 TI - [Endotoxin-induced lung injury. The roles of leukocytes and oxidants, and the efficacies of steroids and antioxidants]. AB - Previous work in our laboratory has shown the relation between leukocytes (WBC) and the generation of oxidants in endotoxin (LPS) shock. The purpose of this study was to find out if WBC-derived oxidants can produce acute lung injury in guinea pigs given LPS. We alos evaluated the efficacies of steroids and antioxidants against the initial changes in LPS-induced lung injury. One group of guinea pigs (200-250 g, male) received 0.7 mg/kg (LD50, 24 hrs.) of E. coli LPS in the peritoneal cavity (group I). The animals in group II received 30 mg/kg of methylprednisolone (MP), followed by intraperitoneal LPS. The animals in group III were given 30 mg/kg of 2-aminomethyl-4-tert-butyl-6-propionylphenol hydrochloride (ONO-3144), a known as antioxidant (OH radical scavenger), and then an injection of LPS. The animals were killed at following time course: 30, 60 or 180 minutes after the LPS injection. Hematological examinations (WBC counts), total cell counts and differential counts in bronchoalveolar lavage (BAL) fluid were done along with light microscopic studies. Superoxide dismutase (SOD) activity, catalase activity and malonaldehyde (MDA) produced as a result of lipid peroxidation in the lung were measured and correlated with histological changes. Survival ratios of the three groups were compared. The results obtained were: 1) Significant leukopenia occurred in all groups. 2) In group I, WBC, especially eosinophils, were recovered by BAL and the total cell number of the BAL fluid had increased by 180 minutes after LPS injection, but MP or ONO-3144 treatment inhibited the migration of WBC (eosinophils and neutrophils) into alveolar lumen after LPS injection. 3) Histologic examinations revealed diffuse edema, hemorrhage, and marked leukocyte infiltration in the alveoli in group I, but not in group II or III. 4) SOD activity in all group diminished below the control level. Catalase activity had significantly increased by 180 minutes after LPS injection in group I, but not in group II or III. MDA had increased remarkably by 60 minutes after injection of LPS in group I, but MP or ONO-3144 treatment prevented such increases. 5) Animals in group II and III survived significantly longer than those in the other group. In conclusion, these findings suggest that LPS provokes WBC-mediated vascular damage in the lung and steroids or antioxidants can minimize the injury and prevent edema formation. Steroids might be useful for achieving quantifiable changes in LPS-induced WBC chemotaxis to the lung and for decreasing oxidant-induced lung injury. PMID- 7775653 TI - [Scanning electron microscopic study of the development of crystalline lens fiber]. AB - To elucidate the 3-dimensional structural development of the albino rabbit lens fiber, and to study how cataracts affect these fibers, the lenses from rabbits 1, 2, 4, and 8 weeks old, and from 8 week old rabbits with cataracts caused by naphthalene were examined with a scanning electron microscope. The results were: 1) Normal rabbit: The ratio of the length of the anterior suture line to the diameter of the lens gradually rose from 1 to 4 weeks and then reached a plateau. The ratio of the length of the posterior suture line was constant from the first week on. Fibers were wider in lenses from older rabbits, except for those in the middle of the suture line. Ball-and-socket junctions were common on the anterior side and were concentrated in the area of the paraanterior suture line of lenses from older animals. The lateral large processes were only noted near the anterior suture line, and in extended direction from its end. The likelihood of finding edge processes, especially in the area of middle anterior and posterior sections, rose with age. 2) Rabbit exposed to Naphthalene: The rate of increase of the length of the anterior suture line and the diameter of the lens were both low, but their ratio did not differ from that of a normal rabbit's lens. On the contrary, the growth rate of the posterior suture line was much greater than that of the diameter. The peculiarity of distribution of edge processes and width found in normal lens fibers was not found in naphthalene-affected fibers. PMID- 7775655 TI - [Treatment of so-called keloid with excision and postoperative electron irradiation]. AB - Between 1988 and 1994, 110 patients with 139 so-called keloids site, which had been treated with conservative therapy were treated with excision, suture, and postoperative irradiation with a 4 MeV electron beam. They were irradiated within one or two days after surgery, for three consecutive days. The total doses were 15 Gy or 18 Gy per fractions for the most part. Control rates of true keloids and hypertrophic scars were 76.0% (57/75) and 93.8% (60/64), respectively, and the overall effectiveness rate was 84.2%. No remarkable side effects were observed. Transient hyperpigmentation was found in 44.6%. No carcinogenesis have been found in our series of patients. Considering the possibility of recurrence, side effects, and carcinogenesis, the indication of our treatment was decided. The result of our treatment using a low-megavolt electron beam was similar to that of published series using a low-energy X-ray. The advantages of the use of electron beam are that the peak of dose is the layer of the occurrence of keloid, and that the depth of penetration of radiation is limited without appreciable effect on the deeper structures. At present, the equipments of low-energy X-ray have been disposed. Our treatment using a electron beam will be an effective treatment. PMID- 7775654 TI - [EEG power and coherence in presenile and senile depression. Characteristic findings related to differences between anxiety type and retardation type]. AB - Quantitative EEG analysis was done on 29 medicated right-handed depressive patients at age over 45 and age and sex matched right-handed 20 normal controls. The patients were all diagnosed as major depression with melancholia by DSM-III-R and were divided into anxiety type (n = 17) and retardation type (n = 12) evaluated with the Hamilton rating scale for depression. Eye closed resting EEGs were recorded on a data recorder from the 16 electrode leads (10-20 system). Artifact rejected 3 minutes EEGs were analyzed by off-line with Fast Fourier Transform from the bilateral frontal (F3, F4), parietal (P3, P4) and occipital (O1, O2) regions. The mean values of absolute amplitude power (microV) and the mean Z scores of inter-, and intrahemispheric coherence were obtained in theta 1 (4.0-6.0 Hz), theta 2 (6.0-8.0 Hz), alpha 1 (8.0-10.5 Hz), alpha 2 (10.5-13.0 Hz), beta 1 (13.0-20.0 Hz), and beta 2 (20.0-40.0 Hz) frequency bands respectively. The main findings were: 1) Beta 1 and beta 2 power were greater in patients with anxiety type depression than in normal controls, and the differences were statistically significant over the parietal and occipital regions in beta 1 and the frontal region in beta 2. The anxiety type was distinguished from the retardation type with the increase of beta 2 power. The retardation type showed higher alpha 1 power over the frontal region and lower alpha 2 power over the occipital region than normal controls. 2) Both types showed greater frontal predominant ratio to the parietal in beta 2 power than did normal controls. The retardation type was distinguished from the anxiety type with the right predominance in beta 1 power over the frontal region. 3) Both groups of patients showed lower frontal interhemispheric coherences than normal controls in each band. In particular, the anxiety type showed significantly lower alpha 2 band and lower beta 1 and beta 2 bands. The parietal interhemispheric coherence was lower in the anxiety type but higher in the retardation type than in normal controls in each band, and this difference was prominent in theta 2 band. 4) The two groups of patients showed higher fronto-parietal intrahemispheric coherences in both hemispheres than the normal controls in each band. Especially, the anxiety type showed higher in theta two and alpha 1 bands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7775656 TI - [Serosal smear cytology in operation for gastric and colonic cancers]. PMID- 7775657 TI - [A case of streptococcal toxic shock syndrome (severe group A streptococcal infections) caused by arthritis]. PMID- 7775658 TI - [Recent advances in esophageal cancer treatment]. PMID- 7775659 TI - Effect of immunization with lutropin-receptor on the ovarian function of rabbits. AB - Three New Zealand white adult female rabbits, designated as A, B, and C, were immunized to produce lutropin receptor antibodies. Antisera inhibited the binding of 125I-hCG to the lutropin receptor and the production of testosterone by hCG stimulated rat Leydig cells. During the study period of, approximately 10 months after the last immunization, rabbits did not ovulate in response to an injection of 75 IU of human chorionic gonadotropin or mating as revealed by laparotomy. As the antibody titers declined, induction of ovulation and laparotomy revealed restoration of ovulation and corpus luteum formation. However, no pregnancy occurred when rabbits A and B were mated and artificially inseminated. These observations indicate that lutropin receptor antibodies can cause infertility in female rabbits. PMID- 7775660 TI - The specificity and affinity of polyclonal antibodies raised in rabbits against a hapten conjugated to rabbit serum albumin. AB - In this study, rabbit antisera to hapten-rabbit serum albumin conjugates were investigated regarding antibody titer, affinity, specificity, and affinity distribution. Methyl phosphonic acid p-amino-phenyl 1,2,2-trimethylpropyldiester (MATP) served as model hapten. Four MATP-rabbit serum albumin conjugates with various hapten densities (with and without spacer) were synthesized and used for immunization of rabbits. Antisera were collected over a 130 day-period and characterized with different ELISA methods. We found that immunogens with rabbit serum albumin gave antisera with lower titers, but similar affinity as compared to polyclonal or monoclonal antibodies obtained with non-rabbit protein as carrier protein. Immunogens with a low hapten density led to higher final titers without affecting antibody affinity or specificity. Immunogens containing a bridging group resulted in higher antibody affinity with a changed specificity. The pattern of antibody affinity distribution differed considerably among individual rabbits and showed a non-Gaussian subpopulation distribution. PMID- 7775661 TI - A non-isotopic immunoassay for guanosine 3':5'-cyclic monophosphate using a cyclic GMP-biotin conjugate as tracer. AB - 2'-O-monosuccinylguanosine 3':5'-cyclic monophosphate was coupled to N-biotinyl 1,8-diamino-3,6-dioxaoctane after converting succinyl-cGMP into its N hydroxysuccinimide active ester. Isolation and purification of the succinyl-cGMP biotin conjugate was performed with FPLC using reversed phase chromatography. The synthesis described yielded a conjugate suitable for use as tracer in immunoassays for the cGMP measurement in plasma and urine samples. Employing biotin as the primary probe in a competitive solid phase immunoassay allows for flexible end point determination by means of commercially available labeled streptavidin derivatives. Streptavidin-europium was used in conjunction with the DELFIA-system for time-resolved fluorometric end point measurement (TR-FIA), streptavidin-horseradish peroxidase was used for colorimetric end point determination (EIA). Both non radioactive immunoassay systems showed excellent correlation with the reference radioimmunoassay, good sensitivity and reproducibility. The succinyl-cGMP-biotin conjugate was shown to be stable for more than two years without any apparent loss of chemical stability or immunological reactivity. PMID- 7775662 TI - Enzyme linked immunosorbent assay for the neurohypophyseal hormones arginine vasotocin and isotocin. AB - A competitive enzyme linked immunosorbent assay (ELISA) using new polyclonal antibodies was developed for the first time for each of two neurohypophyseal hormones: arginine vasotocin (AVT, ubiquitous in vertebrates) and isotocin (IT, restricted to teleost fish). The antibodies obtained were highly specific, showed no cross-reaction between the two peptides and were able to suppress the activity of the peptides in in vitro bioassays. An original feature of the assays was the covalent binding of the peptidic antigen to Covalink microplates. Competition was thereafter made between this bound antigen and the antigen in samples, for a fixed amount of the relevant antibody. Revelation used peroxidase-labeled antibodies. These ELISAs were sensitive enough to detect 1 ng/ml and 0.1 ng/ml for AVT and IT respectively. Moreover, for the first time, the two hormones were measured separately, each in the presence of the other, and shown to exist as circulating hormones in fish. PMID- 7775663 TI - A noncompetitive enzyme immunoassay for rat prolactin. AB - A sensitive and specific noncompetitive rat prolactin (rPRL) enzyme immunoassay (EIA) is described. In this assay, the same rabbit anti-rPRL antibody is both adsorbed to a solid-phase support, i.e. 96-well microtiter plates and conjugated covalently to peroxidase as a tracer. PRL being sandwiched between antibody molecules, the enzymatic activity is thus proportional to the amount of rPRL concentration. This assay was found highly specific for rat PRL and displayed a sensitivity of 12.5 pg/well (0.125 ng/ml) of NIH-RP2 equivalents. The intra-assay and inter-assay coefficients of variation were less than 10% over a wide range of rPRL concentration (0.25-40 ng/ml). This rPRL-EIA permits to quantify PRL in culture media or biological samples containing up to 25% of plasma. Comparison with a radioimmunoassay revealed a good correlation (r = 0.984, the slope = 1.04). This EIA is rapid, results being obtained within 4h30 or 18h30 depending on the nature of the biological samples. The tracer, easily performed with a low cost enzyme, can be stored for very long durations. Thus, this sensitive and rapid assay provides a valuable method for measuring rPRL. PMID- 7775664 TI - Detection of soluble T cell receptor-releasing cells by ELISPOT assay. AB - A specific and sensitive enzyme-linked immunospot (ELISPOT) assay has been developed for the detection and enumeration of soluble T cell receptor (TCR) releasing cells. Using this method, we readily detected at the single cell level the release of soluble TCR by living T lymphoma cells (MT-2 and HSB-2) but not by human B lymphoma cells (DAKIKI), mouse hepatoma cells (MH134) and dead MT-2. Furthermore, distinct spots in MT-2 cell culture were not visualized using several monoclonal antibodies against antigens unrelated to TCRs as a primary antibody. The specific and quantitative detection of soluble TCR-releasing cells using ELISPOT assay will certainly provide a valuable tool to better characterize soluble TCRs and their relationship to immune regulation and a number of diseases. PMID- 7775665 TI - Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. AB - We previously reported that low-dose doxycycline (DOXY) therapy reduces host derived collagenase activity in gingival tissue of adult periodontitis (AP) patients. However, it was not clear whether this in vivo effect was direct or indirect. In the present study, inflamed human gingival tissue, obtained from AP patients during periodontal surgery, was extracted and the extracts partially purified by (NH4)2SO4 precipitation. The extracts were then analyzed for collagenase activity using SDS-PAGE/fluorography/laser densitometry, and for gelatinase activity using type I gelatin zymography as well as a new quantitative assay using biotinylated type I gelatin as substrate. DOXY was added to the incubation mixture at a final concentration of 0-1000 microM. The concentration of DOXY required to inhibit 50% of the gingival tissue collagenase (IC50) was found to be 16-18 microM in the presence or absence of 1.2 mM APMA (an optimal organomercurial activator of latent procollagenases); this IC50 for DOXY was similar to that exhibited for collagenase or matrix metalloproteinase (MMP)-8 from polymorphonuclear leukocytes (PMNs) and from gingival crevicular fluid (GCF) of AP patients. Of interest, Porphyromonas gingivalis collagenase was also inhibited by similar DOXY levels (IC50 = 15 microM), however the collagenase activity observed in the gingival tissue extracts was found to be of mammalian not bacterial origin based on the production of the specific alpha A (3/4) and alpha B (1/4) collagen degradation fragments. In contrast, the inhibition of collagenase purified from culture media of human gingival fibroblasts (MMP-1) required much greater DOXY levels (IC50 = 280 microM). The predominant molecular forms of gelatinolytic activity presented in the AP patients gingival tissue extracts were found to closely correspond to the 92 kD PMN-type gelatinase (MMP 9) although small quantities of 72 kD fibroblast-type gelatinase (MMP-2), and some other low molecular weight gelatinases, were also detected. The IC50 of DOXY versus gingival tissue gelatinolytic activity was estimated at 30-50 microM measure using either type I gelatin zymography or the biotinylated type I gelatin assay. We conclude that MMPS in inflamed gingival tissue of AP patients, like those in GCF, originate primarily from infiltrating PMNs rather than resident gingival cells (fibroblasts and epithelial cells) or monocyte/macrophages, and that their pathologically-elevated tissue-degrading activities can be directly inhibited by pharmacologic levels of doxycycline. PMID- 7775666 TI - Ex vivo studies of polymorphonuclear neutrophils from patients with early-onset periodontitis (III). CR3 and LFA-1 expression by peripheral blood and gingival crevicular polymorphonuclear neutrophils. AB - In this study, we assessed the LFA-1 (CD18/CD11a) and CR3 (CD18/CD11b) expression on peripheral polymorphonuclear leukocytes (PB-PMN) and crevicular fluid polymorphonuclear leukocytes (CF-PMN), by subjects with a healthy periodontium (n = 7), gingivitis (n = 8), early-onset periodontitis (n = 17) and adult periodontitis (n = 8). Using flow cytometry analysis, the %s of CD18, CD11a and CD11b positive cells and the absolute numbers of fluorescent molecules were determined. No significant difference could be found among the 4 groups, for these 2 kinds of parameters, in PB-PMN or CF-PMN. However, a great difference could be noted between the results obtained from PB-PMN and those obtained from CF-PMN. The %s of positive CF-PMN were significantly lower than those of PB-PMN for the 3 sub-units (p < 0.001). The levels of CD18 and CD11b expressed by CF-PMN were higher than those expressed by PB-PMN and the difference was significant for CD11b (p < 0.001). On the contrary, the level of CD11a expressed on CF-PMN was significantly lower than that expressed by PB-PMN (p < 0.001). Hence, our current results show that early-onset periodontitis PMN can be quite normal and this fact is not surprising insofar as, in our study, these cells were perfectly functional and all the subjects were in good health. We concluded that the analysis of the leukocyte adhesion receptors expression on PB-PMN does not appear useful for helping to establish a differential diagnosis between the different forms of periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775667 TI - Periodontal disease and type I diabetes mellitus in children and adolescents. AB - This study compared the periodontal status of a juvenile diabetic study group with that of a non-diabetic control group similar in age and sex. The study group consisted of 26 type I diabetic patients with an average age of 13.42 years and 24 control subjects of similar age. The diabetic subjects were evaluated with glycosylated hemoglobin (GHb) to obtain a measure of diabetic control. Clinical periodontal evaluations were performed for all teeth in each subject, and consisted of the plaque index, gingival fluid flow, gingival index, probing depths, clinical attachment levels, recession, and bleeding on probing. Analysis of the data demonstrated no statistically significant differences in the overall means for the 2 groups for average attachment loss, probing depths, recession, gingival index, plaque index, gingival fluid flow, or bleeding on probing. There was no significant association between the level of control of diabetes (GHb) and clinical variables. However, comparisons based on site-specific measurements showed the gingival index to be somewhat higher among the diabetics (p = 0.0002), and examination of interaction effect plots showed the diabetic group to have higher average gingival index for most teeth and higher or the same plaque index levels on all teeth relative to controls. Thus, a young study population with type I diabetes mellitus was found to have significantly increased severity of inflammatory gingival disease compared to controls of similar age. PMID- 7775668 TI - The microbiota of osseointegrated implants in patients with a history of periodontal disease. AB - The purpose of this study was to determine the presence of suspected periodontal pathogens in the peri-implant microflora of osseointegrated implants exposed 3 and 6 months to the oral environment of patients previously treated for periodontal disease. Subgingival microbial samples were taken in the deepest residual pocket of each quadrant in 10 patients before placement of ITI implants and in 10 patients before abutment connection of Branemark implants. The samples were cultured using continuous anaerobic techniques. 4 patients were positive for P. gingivalis, 13 for P. intermedia, 2 for A. actinomycetemcomitans, 16 for Fusobacterium, 7 for C. rectus and 12 showed microscopic evidence of spirochetes. After 3 and 6 months exposure of the implants to the oral environment, one sample was obtained from the peri-implant sulcus in each patient. P. gingivalis was found in 2 patients in the peri-implant samples after 3 and 6 months. 6 peri implant samples were positive for P. intermedia after 3 months, 7 after 6 months. Fusobacterium was present in 13 peri-implant samples after 3, and in 12 samples after 6 months. 4 patients showed evidence of for C. rectus after 3 months, 2 after 6 months. Spirochetes were seen in 3 peri-implant samples after 3 and in 5 after 6 months. None of the implants were found to be colonized by A. actinomycetemcomitans, although the organism was detected on teeth in 1 individual. Similar distribution patterns were noted for ITI and Branemark type implants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775669 TI - A comparison of partial and full mouth scoring of plaque and gingivitis in oral hygiene studies. AB - The clinical testing necessary to demonstrate the safety and efficacy of new toothbrushes is complex and expensive. Any modification of methodology that could reduce complexity and cost without compromising quality would benefit both investigators and the public. Results from an 8-week toothbrush study were assessed for the use of partial as compared to full-mouth evaluations. The potential utility of an objective, minimally-invasive bleeding index for the evaluation of gingivitis was also tested. 2 partial evaluations, half-mouth and molar/anteriors, revealed decrements in modified gingival index (MGI), bleeding index and plaque index that were statistically significant and similar in magnitude to those derived from full-mouth examinations. % decrements in MGI and bleeding index based on the Ramfjord teeth were not significant statistically. Results for the new sulcular bleeding index were essentially similar to those for the MGI. However, the bleeding index offered the advantage of improved objectivity for use in both white and non-white subjects. These results suggest that partial evaluations and the new bleeding index may be useful elements in the design of toothbrush efficacy studies. PMID- 7775670 TI - Personal risk factors for generalized periodontitis. AB - Periodontitis is generally considered to be a consequence of an unfavourable host parasite interaction in which bacteria are the determinants of disease. An intense search continues for the bacteria, specific or non-specific, that are responsible for periodontitis and various forms of the periodontal diseases have been associated with, and are widely believed to be caused by, specific bacterial groups. However, the distribution of periodontopathic bacteria is far wider than the distribution of periodontitis, indicating that the association between bacteria and periodontitis is weak. This paper proposes a paradigm for the etiology of generalized periodontitis in which 'host' factors are not only those triggered by bacteria (the agent) but are also those personal factors that influence the outcome of the host/parasite relationship. The personal factors that diminish the efficiency of host defense may include psycho-social stress from the social environment, factors from the lifestyle such as diet, smoking and alcoholism and systemic factors such as intercurrent disease or deficiencies within the immune/inflammatory system. A model is described in which the interaction of personal factors with the social environment provides the potential for the initiation of periodontitis. Biological variation is significant and the combination of factors that cause generalized periodontitis or any other chronic disease in one individual may not result in dental or any other chronic disease in another. PMID- 7775671 TI - Relationship between CPITN and periodontal attachment loss findings in an adult population. AB - This study investigates the relationship between CPITN findings and the prevalence and severity of periodontal attachment loss in a rural Kenyan population comprising 1131 persons aged 15-65 years. All persons were examined for calculus, gingival bleeding, pocket depths and attachment loss levels on 4 sites of each tooth present. Recordings of bleeding, calculus and pocket depths were used to compute CPITN scores based on the 10 index teeth originally proposed, and these CPITN scores were subsequently related to the attachment loss findings derived from the full-mouth assessment. In most cases, persons with a CPITN score < or = 1 did not have attachment loss > or = 4 mm. However, among 40+ year-old persons with CPITN score 2 over 90% had attachment loss > or = 4 mm and over 50% of the 50+ year-olds with CPITN score 3 had attachment loss > or = 6 mm. Less than 20% of the 15-29 year-olds with CPITN score 3 had attachment loss > or = 6 mm, and usually the attachment loss levels ranged between 0 and 3 mm. Beyond the age of 35 years over 10% of the sextants with CPITN score 0 had attachment loss > or = 4 mm. Below the age of 35 years more than one third of all sextants with CPITN score 3 had attachment loss levels < or = 3 mm. Thus, the CPITN findings overestimate both prevalence and severity of periodontal attachment loss among the younger age groups and underestimate these parameters among elderly subject. PMID- 7775672 TI - Prognostic criteria for the efficiency of non-surgical periodontal therapy in advanced periodontitis. AB - The aim of the study was to find out which clinical, radiographic and microbiological variables can be used as prognostic criteria for the efficiency of the commonly used initial treatment protocol comprising scaling, root planning and instruction on oral hygiene in advanced adult periodontitis. 46 patients (mean age 48 years) with untreated, advanced periodontitis volunteered for the study. The clinical examination included recordings of plaque, gingival and calculus indices, probing pocket depths, bleeding and suppuration after probing, probing attachment levels and furcation involvements. Infrabony and furcation lesions were assessed from panoramic radiographs. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were cultured from the deepest, most inflamed periodontal Pockets, from surface of the tongue and from saliva. 3 months after the completion of non-surgical treatment comprising meticulous scaling and root planing and instruction on oral hygiene, the healing was assessed clinically, and 13 patients were assigned to a maintenance care programme (MC) and 33 to further treatment procedures (FT). Evaluation of the baseline clinical and radiographic data showed a significantly higher %s of > or = 6 mm deep periodontal pockets, surfaces with suppuration, and sites with subgingival calculus, as well as higher numbers of infrabony lesions, in FT patients than in MC-patients. Subgingival A. actinomycetemcomitans was isolated at baseline in 55% of the FT-patients and in 38% of the MC-patients, and P. gingivalis in 27% and 23%, respectively. A. actinomycetemcomitans was eradicated by non-surgical treatment from only one patient. P. gingivalis was detected in 15% of the patients in both groups after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775673 TI - Crevicular interleukin-1 beta in moderate and severe periodontitis patients and the effect of phase I periodontal treatment. AB - Interleukin-1 beta (IL-1 beta), a potent stimulator of bone resorption, has been implicated in the pathogenesis of periodontal destruction. However, the relationship between cytokines and periodontal disease has not been studied sufficiently to allow definitive conclusions. The aims of this study are to investigate crevicular IL-1 beta and the clinical status of patients with periodontitis and the effect of phase I periodontal therapy on levels of IL-1 beta. For this study, 130 gingival crevicular fluid (GCF) samples were harvested from non-inflamed (15) and diseased sites (115) in 11 patients with periodontitis. The gingival index (GI) and probing depth (PD) of each site was recorded initially and one month after treatment. The amount of IL-1 beta in the GCF was measured by enzyme-linked immunosorbent assay (ELISA) using an antibody specific for this cytokine. Before treatment, IL-1 beta was found in 12 of 15 non inflamed gingival crevices and in 112 of 115 diseased pockets. The amount of IL-1 beta varied from 4.03 to 511.12 pg/site. The average amount of IL-1 beta from diseased sites was 3-fold greater than that from non-inflamed sites. Both total amount of IL-1 beta and the GCF volume, but not IL-1 beta concentration, were found to be correlated, positively, with GI score and PD. After therapy, 63 sites from 7 patients were re-examined, and the amount of IL-1 beta in 49 of 63 sites was found to have declined. These data suggest that the amount of crevicular IL-1 beta is closely associated with periodontal status. This relationship may be valuable in monitoring periodontal disease activity. PMID- 7775674 TI - Observations of root surfaces from patients with early-onset periodontitis and leukocyte adhesion deficiency. AB - The purpose of this investigation was to report observations of the root surfaces of teeth from 2 siblings with leukocyte adhesion deficiency (LAD). In previous publications, the clinical, radiographic and immunologic findings in the family were presented. 38 permanent teeth from the 2 siblings were prepared for microscopic examination, 11 for light microscopy (LM), and 27 for scanning electron microscopy (SEM). In addition, 8 healthy teeth obtained from 2 patients requiring extractions for orthodontic treatment served as controls. LM observations on healthy teeth revealed cementum with normal structural appearance which exhibited a mosaic or mogul-like pattern with SEM. In LAD specimens, cementum apical to the dentogingival junction exhibited resorption lacunae and areas of poor structural definition characterized by aplasia and hypoplasia (hypomineralization). Areas of hypoplasia presented as distinct irregular surfaces with a pebbly or globular-like appearance. Alteration in cementum formation and maturation may play a role in the etiology of early-onset periodontitis. PMID- 7775675 TI - The effectiveness of an electronic toothbrush in the removal of established plaque and treatment of gingivitis. AB - The purpose of the present study was to evaluate the effect of an electronic toothbrush on established plaque and gingivitis in a 5-month clinical trial. This electronic toothbrush sends approximately a 0.15 mA current through the brushhead which presumedly enhances the efficacy of the brush in plaque elimination. For this study, 80 volunteers (non-dental University students) were selected on the basis of having moderate gingival inflammation. At baseline, plaque and bleeding upon probing were assessed on the vestibular, mesio-vestibular, distovestibular and lingual surfaces using the 'half-mouth' design. After 2-months and 5-months, these clinical indices were again recorded. At each assessment, the participants received a new brushhead. All baseline indices appeared to be well-balanced. A mean Silness and Loe plaque score of 1.70 and 1.64 were found in the control and test groups, respectively. Little change was observed from baseline to 5-months. The Quigley and Hein plaque index behaved comparably. The mean bleeding upon probing score at baseline was 1.43 and 1.39 for the control and test group, respectively. Little to no improvement was observed in the course of this study. No beneficial effect could be shown for this 'electronic' design of manual toothbrush. PMID- 7775676 TI - Periodontal findings in spouses. A clinical, radiographic and microbiological study. AB - Clinical, radiographic and microbiological examination of periodontal conditions was carried out in 2 groups of married couples to assess similarities between husband and wife. The diseased probands (n = 10) exhibited advanced periodontitis and the healthy ones (n = 10) were periodontally normal. The clinical examination comprised the assessment of plaque, probing pocket depths, gingival bleeding on probing, suppuration, supragingival and subgingival calculus. The extent and type of alveolar bone loss was determined from panoramic radiographs. Bacterial samples were taken from the 6 deepest and most inflamed periodontal pockets and from stimulated saliva. The samples were cultured for Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus and Peptostreptococcus micros. The mean detection frequency of moderately deep pockets (4-5 mm) and deep pockets (> or = 6 mm) was significantly higher in the diseased probands than in their spouses. The mean detection frequency of moderately deep pockets was significantly higher in the spouses of the diseased probands than in the spouses of the healthy ones. Deep pockets were found in 6 spouses of the diseased probands, whereas only in 2 spouses of the healthy ones. Both diseased proband and his/her spouse harbored A. actinomycetemcomitans, P. gingivalis, P. intermedia, C. rectus and P. micros in 4, 6, 9, 9 and 4 couples, respectively. Both healthy proband and his/her spouse harbored the pathogens in 0, 1, 9, 5 and 3 couples, respectively. P. gingivalis was found in 7 spouses of the diseased probands, but only in 2 spouses of the healthy ones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775677 TI - The young mind. PMID- 7775678 TI - Class II Vitremer restoration of primary molars. AB - Several resin-modified, glass-ionomer cements have proved successful when used in Class III and Class V cavities in primary teeth. One of them, Vitremer, is proving to be very durable when used in Class I and Class II cavities in primary teeth. The material is handled as quickly and easily as silver amalgam. The components of the Vitremer Tri-Cure System are: Primer, Glass powder, Liquid, and Resin gloss. In addition to a light-curing mechanism, Vitremer hardens by the acid base, glass-ionomer reaction, and a chemical "dark cure", catalyzed by a reduction/oxidation reaction. Over 600 Class II Vitremer restorations have been placed and over 250 have been in the teeth long enough (12 to 18 months) to be observed regularly. PMID- 7775679 TI - Polycarboxylate cement as a cavity-sealing material for the calcium hydroxide pulpotomy: a retrospective study. AB - Polycarboxylate cement was evaluated as a cavity-sealing material in calcium hydroxide pulpotomies of primary molars. The lifespan of these teeth (N = 55) were compared with that of the corresponding teeth on the contralateral sides. The success rate for the treatment was 75.5 percent after one year and at least 61.9 percent after two years. Significant shorter life-spans were found in primary teeth with pulpotomy than in those without it. However, polycarboxylate cement can be a suitable alternative for zinc oxide-eugenol as a cavity sealing material in calcium hydroxide pulpotomies. PMID- 7775680 TI - Orthodontic diagnosis and treatment planning in the primary dentition. AB - Early recognition of malocclusions is in the hands of the primary care providers. Pediatric and general dentists should be familiar with conditions that are known to interfere with growth and development of a child. Conditions such as early loss of primary teeth, anterior and posterior crossbites, and some Class III skeletal problems can be treated in the primary dentition to facilitate normal growth and development and offered some benefit to the patients. On the other hand, aggressive arch length modulation, Class II correction and intervention for vertical problems, including non-nutritive sucking habits, is largely unwarranted. PMID- 7775681 TI - A longitudinal assessment of predictive value of a caries activity test in young children. AB - A longitudinal study was conducted in Okayama, Japan to investigate the predictive value of a caries activity test (Cariostat). The subjects were 100 children who participated in routine dental examinations at 18, 24 and 36 months. Results indicated caries prevalence of 9% at 18 months, 21 percent at 24 months and 70 percent at 36 months. Cariostat scores at each age were correlated with dmft at 36 months and with whether or not child was caries-free at 36 months. Cariostat scores at each age showed good validity (sensitivity + specificity) for whether or not child was caries-free at 36 months. These results indicated that caries activity test, Cariostat, was effective for predicting caries occurrence in young children. PMID- 7775682 TI - How important are techniques? The empathic approach to working with children. AB - The author presents behavior management as essentially anxiety management, not alone in the child but in ourselves as well. Behaviorist and humanist psychologies are discussed. The author is critical of the teaching that behavior management can be taught as a technique: if a specific management technique is used, the child will behave in a certain way. Several techniques are discussed. Voice control and facial expression are discussed. Physical restraints are considered and their use discussed, along with their long-term effects. Empathy is discussed at length. PMID- 7775683 TI - Anxiety reduction with nitrous oxide: a permanent solution? AB - Anxiety scores of highly fearful children were registered during a control period after their curative treatment. The average length of the control period was seventy-two weeks. The anxiety scores of the children who were treated curatively with the aid of nitrous oxide were significantly lower than those of children from a behavioral management group. All the semiannual check-ups were performed without the use of nitrous oxide. Anxiety scores of all the children during the control period correlated closely with the anxiety scores of the curative treatment before and after the control period. It was concluded that nitrous oxide helps children to lower their anxiety levels during a long period after treatment. Influencing anxiety in highly anxious children might be characterized as a long-term process. PMID- 7775684 TI - Transcutaneous electrical nerve stimulation (TENS) for pain management during cavity preparations in pediatric patients. AB - The purpose of this study was to evaluate the effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS) in pain reduction during cavity preparations in pediatric patients. Twenty patients, ages eight to fourteen years, were treated for Class I amalgam restorations in mandibular first permanent molars using TENS in a double blind protocol. Randomized assignments were made for ten experimental and ten control patients. Using the visual analogue scale, the ANOVA test indicated a significant decrease (p < 0.01) in patient ratings between the TENS experimental and the control group. It can be concluded there was a statistically significant decrease in the pain perceptions of pediatric patients during Class I amalgam cavity preparations in mandibular first permanent molars. PMID- 7775685 TI - Child abuse education: do not overlook dental professionals. AB - Dental professionals are mandated by law to report suspicions of child abuse and neglect (CAN), but surveys show dentists do not fulfill their obligation to report. Even though more than 50 percent of physical abuse occurs to the head and facial area, and more than 70 percent of child abuse and neglect fatalities are caused by injuries to the head and neck, dental professionals are often overlooked in efforts to educate the public on the problem. Pre-program questionnaires completed by dental professionals attending an educational program on identifying and reporting child abuse indicated that 70 percent had no previous training in identifying and reporting child abuse, 65 percent had suspected child abuse in their patients, but only 19 percent reported the abuse. As a result of this educational program, it is expected that some children in the state of Indiana will receive improved assessments by dentists and suspected child abuse and neglect will be reported to the proper agencies when identified. PMID- 7775686 TI - Your pediatric patients may be moving away from your practice. AB - A review is provided of general population movements to different places of residence. Emphasis is placed on the need for practitioners to consider the impact on young children as they leave familiar surroundings and enter the world of a new residence. PMID- 7775687 TI - Turner's syndrome in association with hemangioma of the parotid gland: report of case. AB - We report a case of Turner's syndrome with hemangioma of the parotid gland. The symptom complex of this syndrome are infantilism, pterygium colli and unusual carrying angle of the elbow. Orodental alterations and multisystem afflictions have been reported in these patients. Diagnosis is based on a combination of the clinical features, buccal smear finding of the absence of barr body and confirmed by karyotyping which can detect mosaic cell lines of the X chromosome. PMID- 7775688 TI - Calcifying odontogenic cyst in infancy: report of case associated with compound odontoma. AB - A case of calcifying odontogenic cyst associated with compound odontoma in an unerupted primary tooth in a three-year-old patient is reported. Some considerations regarding the age of the patient, differential diagnosis and treatment are discussed. Although the cyst can occur at any age, the majority of cases appear before the fourth decade of life. This malady represents less than 2 percent of all odontogenic tumors and cysts. PMID- 7775689 TI - Fluid management in ARDS: "keep them dry" or does it matter? PMID- 7775690 TI - Treatment of surgical and non-surgical septic multiorgan failure with bicarbonate hemodialysis and sequential hemofiltration. AB - OBJECTIVE: Hospital mortality of patients with septic multiorgan failure (MOF) is still around 95%. The present study investigates whether this high mortality could be significantly reduced by the addition of sequential hemofiltration (SH) with bicarbonate hemodialysis (HD) to the currently used life supportive measures. DESIGN: 35 (18 surgical and 17 nonsurgical) patients, with 3 or more organ failures, had daily sessions of zero balance SH, for periods ranging from 2 22 days. MEASUREMENTS AND RESULTS: SH induced significant improvement of PaO2/100 FIO2, Apache II score, MAP, as well as blood chemistry in survivors. Dying patients had less marked improvement of blood oxygenation, non-significant changes in other variables, in addition to low MAP before and after SH, as well as marked hemodynamic unstability during the procedure. The observed hospital mortality was 38% for the surgical group, and 35.3% for the medical patients (n.s.). CONCLUSIONS: Mortality observed in this retrospective, uncontrolled study was significantly lower than that currently observed with conventional supportive therapy, with or without the addition of other forms of blood purification, e.g. CAVH and CAVHD. This improvement in results appears to be related to the property of SH to completely clear 90% of the blood from mediators of inflammation in only one passage through the hemofilter, and to better tolerance of HD done using bicarbonate buffer. A definite evaluation of this technique will be eventually reached by a programmed, appropriate sample size study, which is out of reach for one individual ICU. PMID- 7775691 TI - Autonomic control of the heart and peripheral vessels in human septic shock. AB - OBJECTIVE: Circulating endotoxin impairs the sympathetic regulation of the cardiovascular system in animals. We studied the changes in the autonomic control of the heart and circulation during septic shock in humans. DESIGN: 12 patients (age 43.0 +/- 6, 17-83 years) were investigated during septic shock (mean duration: 3.5 +/- 0.5 days) and during recovery, fluctuations in R-R interval, invasive arterial pressure (AP) and peripheral arteriolar circulation (PC, photoplethysmography) were evaluated by spectral analysis as a validated noninvasive measure of sympathovagal tone. Apache II score was adopted as the disease severity index. Low frequency components (0.03-0.15 Hz) of the frequency spectra were expressed as relative to the overall variability (LFnu) for each cardiovascular variable. RESULTS: LFnu were low or absent during shock but, in the 10 patients who recovered, increased by the time of discharge (post-shock). R R LFnu increased from 17 +/- 6 to 47 +/- 9 (p < 0.03), AP LFnu from 6 +/- 3 to 35 +/- 4 (p < 0.02) and PC LFnu from 18 +/- 3 to 66 +/- 4 (p < 0.001). Apache II fell from 23.1 +/- 1, at admission, to 14.8 +/- 1.8 at discharge (p < 0.005). Two patients died showing no LFnu increase. CONCLUSION: Reduced LF components of the variability of cardiovascular signals are characteristic of septic shock, confirming the presence of abnormal autonomic control. Restored sympathetic (LF) modulation seems to be associated with a favourable prognosis. PMID- 7775692 TI - Use of morphine cholescintigraphy in the diagnosis of acute cholecystitis in critically ill patients. AB - OBJECTIVE: To determine the efficacy of morphine enhanced radionuclide cholescintigraphy (MC) in the diagnosis of acute cholecystitis (AC) in critically ill patients. DESIGN: Retrospective chart review. SETTING: 2 university hospitals. PATIENTS AND METHODS: Records of all ICU patients who underwent MC as part of an evaluation for AC over an 8 year period were reviewed (n = 45). All patients initially had standard radionuclide cholescintigraphy (RC) performed which showed nonvisualization of the gallbladder (GB) and were then given morphine sulfate (0.05-0.1 mg/kg i.v.). RESULTS: The mean age was 54 years (range 18-84 years). Risk factors for AC included fasting in 41 patients (mean 12.4 days) and total parenteral nutrition in 32 patients. Signs of biliary sepsis included temperature > 100 degrees F in 38 patients, WBC > 10,000/ml3 in 40 patients, abdominal pain in 29 patients, and abnormal liver function tests in 42 patients. 23 patients had GB ultrasonography, with 7 showing stones. MC was positive (non-visualization) in 16 patients and negative (GB visualized) in 29, including 4 with gallstones. All patients in whom the GB was visualized did so within 1 h. There were 13 patients with positive MC who underwent operation; 12 had AC (9 acalculous, 3 calculous). Three patients were treated medically and recovered (false positive). All 29 patients with negative MC were true negatives. Overall, MC had an accuracy of 91%, sensitivity of 100%, specificity of 88%, positive predictive value of 75%, and negative predictive value of 100%. CONCLUSION: MC is a useful test in the evaluation of critically ill patients for suspected AC, particularly in patients with known risk factors or documented gallstones. PMID- 7775693 TI - Predictive value of tetrapolar body impedance measurements for hydration status in critically ill patients. AB - OBJECTIVE: To design and evaluate a simple and rapid method to predict body hydration status in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 31 consecutive patients. METHODS: All patients were classified daily for hydration status by the attending physician based on clinical impression, weight changes and laboratory measurements. The hydration status was scored as 'dehydrated', 'euvolemic' or 'edematous'. The total body impedance was measured daily by a tetrapolar impedance technique. RESULTS: Resistances > 700 omega were found in dehydrated subjects and resistances of < 400 omega in edematous patients. Weight gain was observed in dehydrated and weight loss in edematous patients. A discriminant analysis was used to create a predictive model for hydration using the daily impedance and weight measurements. If a cutoff point of 60% for the predicted classification was used to categorize the patient's hydration as dehydrated, euvolemic and edematous, no false positive predictions were observed for the dehydrated or the edematous state. CONCLUSION: Impedance measurements are in close agreement with the clinical impression of hydration of critically ill patients. Future investigations must elucidate the clinical importance. PMID- 7775694 TI - No-reflow after cardiac arrest. AB - OBJECTIVE: Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest. DESIGN: Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation. MEASUREMENTS AND RESULTS: Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, no-reflow affected 21 +/- 5%, 42 +/- 38% and 70 +/- 27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7 +/- 11% after 5 min cardiac arrest (p < 0.05) but persisted in 30 +/- 11% and 65 +/- 21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.). CONCLUSION: Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of post-resuscitation brain pathology. PMID- 7775695 TI - An experimental set-up to test heat-moisture exchangers. AB - OBJECTIVES: The purpose of this study was to build an experimental set-up to assess continuously the humidification, heating and resistance properties of heat moisture exchangers (HMEs) under clinical conditions. DESIGN: The experimental set-up consists of a patient model, measurement systems and a ventilator. SETTING: Surgical ICU, University Hospital of Rotterdam. MATERIALS: A clinically used HME. MEASUREMENTS AND RESULTS: The air flow, pressure in the ventilation circuit, pressure difference over the HME, and partial water vapour pressure and temperature at each side of the HME were measured. The resistance, absolute humidity, humidification efficiency and temperature difference at the patient side of the HME were calculated. Measurements were performed during 24 h. The temperature output, humidity output and lung mechanics of the patient model were similar to values found in mechanically ventilated patients. The measurement system was in agreement with the ISO draft standard and was capable of measuring dynamic variation of water and heat exchange over the range of a clinically used ventilator setting. CONCLUSION: The experimental set-up described is reliable for evaluating HMEs and can also be used for future clinical evaluation of HMEs. The main advantages of this set-up over those described previously are: (i) measurements of dynamic variations of water and heat exchange; (ii) on-line measurements of expiratory, as well as inspiratory resistance. PMID- 7775696 TI - Clinical validation of the Deltatrac monitoring system in mechanically ventilated patients. AB - OBJECTIVE: To evaluate a monitor of pulmonary gas exchange (Deltatrac, Datex) in a clinical setting. DESIGN: After in vitro evaluation, comparison over 2 min between VO2 and VCO2 values measured by the Deltatrac and the Douglas bag technique. Comparisons were also achieved over 8 h periods between the Deltatrac and a system using a mass-spectrometer. SETTING: Polyvalent intensive care unit (ICU 15 beds) in a 1200 bed general hospital. PATIENTS: Comparison with the Douglas bag technique in 10 patients undergoing controlled ventilation. Comparison with the mass-spectrometer system in 25 other patients undergoing controlled or pressure support ventilation. MEASUREMENTS AND RESULTS: Compared to the results obtained by the Douglas bag technique, the bias (+/- 2 SD) for VO2 and VCO2 was -3.5 +/- 26.6 and 6.1 +/- 12.7 ml.min-1, respectively. By comparison with the mass-spectrometer system, the bias for VO2 and RQ was -5.8 +/- 16.0 ml.min-1 and 0.018 +/- 0.048, respectively. No drift between the two systems was observed over time. CONCLUSIONS: The Deltatrac appears suitable for VO2 and VCO2 measurements in ventilated patients and equivalent to a mass-spectrometer system for long term measurements. PMID- 7775697 TI - Cardiac output measurement by the thermodilution method: an in vitro test of accuracy of three commercially available automatic cardiac output computers. AB - OBJECTIVE: To describe the accuracy and the reproducibility of the thermodilution flow measurements obtained using 3 commercially available cardiac output computers commonly used in intensive care units. DESIGN: An experimental "in vitro" study. Twelve different values of control flow (Qctr) were measured (Qmsr) using 3 different cardiac output computers (Abbott Critical Care System, Oximetrix 3 SvO2/CO Computer, Baxter Oximeter/Cardiac Output Computer SAT-1; American Edwards Laboratories, 9520 A Cardiac Output Computer). Standard equipment and techniques were employed, taking account of the specific weight and heat of warm water relative to blood. In addition, separate sets of measurements were performed in order to investigate the effect on Qmsr of some variables which may influence the "indicator" loss (time for injection, depth of immersion of the catheter, temperature of the injected fluid). SETTING: Our laboratory, inside the intensive care unit. MEASUREMENTS AND RESULTS: The analysis of the linear regression of Qmsr versus Qctr (r values between 0.992 and 0.984; residual standard deviation values comprised between 0.24 and 0.49 l/min; intercepts and slopes not significantly different from identity line), the values of the percentage errors (PE = [Qctr-Qmsr].100/Qctr; PE mean values 7.9, 5.0 and 13.1), and those of the coefficients of variability (CV = standard deviation mean value, %; CV mean values 5.4, 5.8 and 4.6), show a good level of accuracy and reproducibility of the measurements. Our data confirm previously reported results. Furthermore, the cumulative effect of variables capable of influencing the "indicator" loss, even if corrected according to the "calculation constant" the manufacturers provide, was found to result in statistically significant changes of Qmsr. CONCLUSION: The accuracy and reproducibility of the automatic cardiac computers tested is sufficient for practical clinical purpose. It may also depend on the modality of injection of the cooling bolus, which may significantly influence the effective "indicator" losses. PMID- 7775698 TI - Characteristics of the ventilator pressure- and flow-trigger variables. AB - Pressure- and flow-triggering are available in the Puritan Bennett 7200ae and Siemens SV 300. Using a mechanical lung model, we described the characteristics of the pressure- and flow-triggered continuous positive airway pressure (CPAP) of both ventilators. In the Puritan Bennett 7200ae, the pressure-triggered CPAP is characterized by the relatively insufficient flow delivery after the triggering, resulting in a greater lung pressure-time product (total PTP) than the flow triggered CPAP. Pressure support of 5 cmH2O results in total PTP less than that with flow-triggered CPAP. In the Siemens SV 300, total PTP with pressure- or flow triggered CPAP is comparable. Total PTP is less with pressure- or flow-triggered CPAP of the Siemens SV 300 than that of the Puritan Bennett 7200ae, respectively. The application of small pressure- or flow-triggered pressure support in the Puritan Bennett 7200ae eliminates the difference. The impact of these differences on patient inspiratory muscle work remains to be determined. PMID- 7775701 TI - Round table conference on clinical trials for the treatment of sepsis. Brussels, March 12-14, 1994. PMID- 7775699 TI - Removal of pro-inflammatory cytokines with renal replacement therapy: sense or nonsense? PMID- 7775703 TI - External high-frequency ventilation in patients with respiratory failure (external ventilation) PMID- 7775702 TI - Withdrawal syndrome following midazolam infusion. PMID- 7775704 TI - Catheter breaking and embolization after right heart catheterization. PMID- 7775700 TI - Central venous catheter infections: concepts and controversies. AB - Central venous catheters (CVCs) are widely used in critically ill patients in intensive care units. However, infectious complications are common and may limit their utility. We critically review the literature to determine the impact of CVC design and composition, insertion site selection, insertion procedures, care and removal of temporary CVCs on infectious complications. Relevant articles were identified and selected for review using a database search (Medline and manual of the English language literature) based upon study design and sample size with an emphasis on prospective randomized trials. To minimize infectious complications and maintain a reasonable cost-benefit ratio, we recommend: i) use a single lumen catheter unless clear indications for a multi-lumen catheter exist; ii) insert the catheter via the subclavian vein if no relative contraindication exists (bleeding diathesis, positive pressure ventilation); iii) disinfect the insertion site employing sterile technique; iv) apply a dry, sterile dressing and change the dressing every other day; v) inspect the insertion site for signs of infection and remove the catheter if pus is present; vi) if a catheter-related infection is suspected, change the catheter over a guidewire and culture the distal segment. The replacement catheter should be removed if an original catheter segment culture is positive. PMID- 7775705 TI - Systemic air embolism after laser resection of a tracheal tumor. PMID- 7775706 TI - Clostridium septicum primary myonecrosis related to cecal neoplasia. PMID- 7775707 TI - Restoration of anterograde flow in acute myocardial infarction: the first 15 years. PMID- 7775708 TI - Lessons we have learned from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries. AB - Thrombolytic therapy remains a mainstay for the treatment of patients with acute myocardial infarction. This therapy has been the subject of intense investigation and multiple studies as well as substantial controversy. Controversial issues include, among others, the specific drug, need for heparin, the relation between time to treatment and outcome and risk/benefit considerations. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial of 41,021 patients addressed many of these issues. The results of the main trial were conclusive--treatment with accelerated tissue-type plasminogen activator (t-PA) resulted in a decreased mortality rate with a 15% reduction (95% confidence interval 5.9 to 21.3) compared with the two streptokinase monotherapy strategies (p = 0.001). Virtually all subgroup analyses, including age, nonanterior infarction location, patients undergoing bypass graft surgery and hypertensive patients, showed remarkable consistency with improved outcome with accelerated t-PA. This reduction in all-cause mortality with accelerated t-PA was associated with a small (absolute 0.2%) but significant increase in hemorrhagic stroke (p = 0.03). A combined end point of death or disabling stroke, or both, was still decreased in the accelerated t-PA group compared with the streptokinase group (p = 0.006). The angiographic substudy evaluated the mechanism of improved outcome and documented that reperfusion therapy works by restoring Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow early, improving left ventricular function and improving mortality. The most favorable outcome seen with t-PA was related to the finding that it resulted in improved TIMI grade 3 flow compared with that for streptokinase. PMID- 7775709 TI - Current issues concerning thrombolytic therapy for acute myocardial infarction. AB - Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS 3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States--tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)--all reduce mortality when given to patients with acute evolving myocardial infarction. Further, it is clear that thrombolytic therapy given to such patients presenting up to 12 h after onset of symptoms reduces the mortality rate by approximately 20%, that aspirin therapy for patients presenting up to 24 h reduces the mortality rate by approximately 23% and that the benefits of thrombolytic therapy and aspirin are additive. Finally, and of most importance, the earlier administration as well as the more widespread use of thrombolytic therapy and aspirin would save many more lives. The totality of evidence clearly indicates that streptokinase produces significantly fewer strokes and cerebral hemorrhages than either t-PA or APSAC. Whether or not accelerated t-PA has a small advantage for mortality is less conclusive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775710 TI - Antithrombotic therapy for acute myocardial infarction. AB - Antithrombotic therapy is clearly beneficial in the treatment of acute myocardial infarction, but the optimal regimen is controversial. Treatment with aspirin leads to substantial and significant reductions in rates of mortality, reinfarction and stroke in patients with acute myocardial infarction, and the benefits are additive with those of thrombolytic therapy. It is unclear whether heparin confers additional net benefits over aspirin alone. In patients receiving aspirin and thrombolytic therapy, there is no mortality benefit from adding delayed subcutaneous heparin, no consistent patency benefit from adding immediate intravenous heparin and no reduction in mortality from adding immediate intravenous heparin, at least for patients treated with streptokinase. However, heparin is consistently associated with increased rates of intracranial and other serious bleeding events when used with both aspirin and thrombolytic therapy. Existing data support the need for further large-scale trials of current and newer antithrombotic regimens in acute myocardial infarction to assess the balance of benefits and risks of these regimens compared with that for aspirin alone. In patients not receiving thrombolytic therapy, randomized trial data are currently insufficient to adequately compare the benefits and risks of adding heparin to aspirin alone. The First American Study of Infarct Survival (ASIS-1) will directly compare the balance of risks and benefits of aspirin alone, aspirin plus intravenous heparin and aspirin plus intravenous hirudin in patients with acute myocardial infarction not receiving thrombolytic therapy. PMID- 7775711 TI - Time to thrombolytic treatment: factors affecting delay and their influence on outcome. AB - One of the major limitations to realizing the full potential of the lifesaving effects of thrombolytic therapy has been the failure to initiate treatment in the first 1 to 1.5 h after symptom onset. The barriers to early treatment include the following: 1) Most patients fail to react rapidly and appropriately to symptoms. 2) Few emergency medical/paramedic systems have established effective triage systems for patients with chest pain or have implemented prehospital electrocardiography to better manage patients with possible acute myocardial infarction. 3) Time to treatment after hospital arrival currently averages 1 to 1.5 h-two to three times longer than what should be necessary to initiate therapy in the patient with typical electrocardiographic and clinical findings and co morbid risk factors. Trials evaluating the effects of prehospital-initiated therapy have all shown trends toward a reduction in mortality (18%) associated with early treatment; however, none has been large enough in and of itself to be conclusive. The goal in the coming years will be to decrease each of these components of delay by developing effective education programs for the lay public, speeding and improving prehospital care by the routine use of electrocardiography and reducing hospital treatment times to < or = 30 min in the "uncomplicated" patient. PMID- 7775712 TI - Hirudin: initial results in acute myocardial infarction, unstable angina and angioplasty. AB - The central role of thrombosis in the pathogenesis of acute myocardial infarction, unstable angina and complications after angioplasty has led to intense interest in developing more effective antithrombotic agents for these disorders. Hirudin, a direct thrombin inhibitor, has undergone extensive testing in experimental models and has recently been evaluated in patients in several pilot trials. Across these three indications, hirudin has been found to achieve a more consistent level of anticoagulation than heparin, as gauged by the activated parital thromboplastin time. Similarly, as an adjunct to thrombolytic therapy in acute myocardial infarction, in the treatment of unstable angina and in support of angioplasty, hirudin appeared to improve indexes of coronary reperfusion and patency. Initial results with clinical end points, including death or myocardial infarction, appeared to favor hirudin over heparin. In several large phase III trials, hirudin is being compared with heparin for all three indications. In the first phases of these trials, the rate of hemorrhagic events, including intracranial hemorrhage, was higher than expected in both the hirudin and heparin arms, which demonstrated that a safety ceiling had been reached. The reformulated Thrombolysis in Myocardial Infarction (TIMI) 9 and Second Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO II) trials are using lower doses of hirudin and heparin, which should allow testing of whether the initial favorable results observed in pilot trials will translate into improved clinical outcome, with an acceptable safety profile, for patients with acute myocardial infarction or unstable angina or those undergoing angioplasty. PMID- 7775713 TI - Cost and quality of life: thrombolysis and primary angioplasty. AB - In an era of limited health care resources, analyses of the cost-effectiveness of cardiac interventions are becoming increasingly important. By generally accepted cost-effectiveness methodologies, the incremental cost for thrombolysis with streptokinase in patients with acute myocardial infarction ranges from approximately $3,500 to approximately $21,000/year of life saved. The estimated incremental cost-effectiveness of tissue-type plasminogen activator (t-PA) compared with streptokinase ranges from approximately $16,000 to $60,000/year of life saved. Pooled results of three randomized trials suggest that primary angioplasty can reduce mortality by as much as 63% without any increase in cost. This potential benefit is substantially greater than the 10% to 15% relative mortality rate reduction for each hour earlier that thrombolytic therapy is administered or the 12% relative benefit suggested for accelerated t-PA compared with that for streptokinase. Large-scale randomized trials are encouraged to determine whether the cost and mortality of population-based strategies using primary angioplasty are better than strategies that rely on intravenous thrombolysis. PMID- 7775714 TI - Angiotensin-converting enzyme inhibitors after myocardial infarction: indications and timing. AB - A number of major studies have examined the impact of angiotensin-converting enzyme inhibitors on mortality in patients with ischemic heart disease. However, in these studies, selection of patients, choice of agent and timing of treatment after myocardial infarction have differed. In the Second Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS II), all patients, unless hypotensive, were treated immediately after thrombolysis with placebo or intravenous enalaprilat followed by oral therapy. In contrast, in the Survival and Ventricular Enlargement (SAVE) study, patients were selected with a reduced radionuclide ejection fraction and without overt ongoing ischemia. Despite these different approaches, both studies were based on the rationale that angiotensin converting enzyme inhibition would beneficially affect infarct expansion and subsequent remodeling. The SAVE study reported a significant reduction in mortality rate (19% risk reduction, 95% confidence interval [CI] 3% to 32%) over an average follow-up period of 42 months, but with no observable impact on mortality rate until almost 1 year into treatment. The CONSENSUS II trial closed prematurely, with no benefit (a 10% increase in risk, 95% CI 7% reduction to 29% increase) apparent from enalapril after 6 months of follow-up. The recently reported but unpublished findings of Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) and the Fourth International Study of Infarct Survival (ISIS-4) indicate a small benefit from early (within 24 h) short-term (4 to 6 weeks) treatment of all patients, unless hypotensive, after a myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775715 TI - Indications for immediate angiotensin-converting enzyme inhibition in patients with acute myocardial infarction. AB - When initiated a few days after myocardial infarction, angiotensin-converting enzyme inhibition exerts beneficial effects on survival and morbidity in patients with asymptomatic left ventricular systolic dysfunction or symptomatic heart failure. During the acute phase of a myocardial infarction, angiotensin converting enzyme inhibition appears to be well tolerated, to prevent the development of heart failure in patients with asymptomatic left ventricular systolic dysfunction and to improve the hemodynamic and clinical variables of heart failure when present. Accordingly, early angiotensin-converting enzyme inhibition is clearly indicated in patients with acute myocardial infarction associated with asymptomatic left ventricular dysfunction or clinical evidence of heart failure. Angiotensin-converting enzyme inhibition may also be beneficial when thrombolytic agents fail to restore coronary patency in patients with acute myocardial infarction. PMID- 7775716 TI - Assessing risk for the onset of functional dependence among older adults: the role of physical performance. AB - BACKGROUND: Approximately 10% of nondisabled, community-dwelling adults aged 75 years and older lose independence in basic activities of daily living (ADLs) each year. The purpose of this study was to evaluate whether simple tests of physical performance could identify older adults, independent in their basic ADLs, who were at increased risk for the onset of functional dependence. METHODS: Among a representative cohort of 1103 community-dwelling adults aged 72 years and older, we evaluated the 664 subjects who were cognitively intact and independent in their basic ADLs at the baseline interview. All cohort members had undergone a comprehensive assessment, including a battery of qualitative and timed performance tests. The main outcome event was the onset of functional dependence, defined as a new disability in one or more of the seven basic ADLs at the 1-year follow-up. RESULTS: Functional dependence developed in 53 (9%) of the 563 subjects who had complete data at the 1-year follow-up. Eight of the 12 qualitative tests and all six of the timed tests were significantly associated (P < .05) with the onset of functional dependence. Both qualitative and timed performance tests demarcated subjects into groups at low and high risk for functional dependence. Four timed tests--chair stands, rapid gait, 360 degrees turn, and bending over--showed a threshold phenomenon, where the rate of new dependence increased slowly with worsening performance until a critical point (or threshold) was reached, and the rate of dependence increased substantially. For timed chair stands, for example, the rates of functional dependence within quarters of worsening performance were 5.3%, 6.3%, 6.7%, and 16%. The risk of functional dependence was markedly elevated (30%-50%) for subjects who were unable to perform the timed tests. CONCLUSIONS: Several simple tests of physical performance were strongly associated with the onset of functional dependence. These results support the potential use of physical performance tests to develop a risk assessment strategy that could identify subgroups of older persons, independent in all ADLs, who are at increased risk for functional dependence. PMID- 7775717 TI - Does oxybutynin add to the effectiveness of prompted voiding for urinary incontinence among nursing home residents? A placebo-controlled trial. AB - OBJECTIVE: To determine if oxybutynin, a bladder relaxant medication, adds to the effectiveness of prompted voiding (PV) in the management of urinary incontinence among nursing home residents. DESIGN: Randomized, placebo-controlled, double blinded, dose-adjusted, crossover trial of oxybutynin added along with PV. SETTING: Seven nursing homes in Los Angeles County, California. PARTICIPANTS: Seventy-five nursing home residents with predominantly urge incontinence, whose incontinence did not respond well to a trial of PV. MAIN OUTCOME MEASURES: The frequency of incontinence, measured as the percentage of hourly (7 AM to 7 PM) physical checks over a 3-day period at which the resident was found wet. RESULTS: Sixty-three (84%) of the residents completed the study. Among those completing the trial, the percent of checks wet went from 26.5% to 23.7% on placebo to 20.2% on active drug. These changes were statistically significant but not clinically meaningful. A clinically significant decrease in the frequency of incontinence, which we defined as a relative reduction in the percent of checks wet of > 33%, occurred in 20 subjects (32%) while on active drug and in 12 subjects (19%) while on placebo (P = .48 by chi-square). Twenty-five subjects (40%) met our "continence criteria" of an average of one or less wet per day while on active drug, and 11 subjects (18%) achieved this goal on placebo (P = .005 by chi square). CONCLUSION: Oxybutynin does not add to the clinical effectiveness of PV in the majority of nursing home residents with urge type urinary incontinence. Selected residents may, however, become more responsive to PV while on oxybutynin. Our data are consistent with other studies of bladder relaxant medications in functionally impaired populations. New drugs and/or other interventions are needed for the large number of incontinent nursing home residents who do not respond well to PV. PMID- 7775718 TI - Epidemiologic and diagnostic aspects of bacteriuria: a longitudinal study in older women. AB - OBJECTIVE: To examine month-by-month variability of bacteriuria in a cohort of older women and to evaluate the performance of rapid diagnostic tests commonly used to indicate the presence of significant bacteriuria. DESIGN: Prospective, observational study. SETTING: Community housing sites and a long-term care institution. PARTICIPANTS: Sixty-one women, mean age 77.6, took part in the study. MEASUREMENTS: Midstream clean-catch urine samples and medical information on subjects were collected at baseline, and then monthly for 6 months. RESULTS: Bacteriuria alone (> or = 10(5) organisms per mL) occurred in 17% of all urine samples (28% of patients), bacteriuria with pyuria in 15% (26% of patients), and bacteriuria with symptoms in 3% (10% of patients). Spontaneous clearance of bacteriuria with pyuria was common (P = .30), as were new occurrences (P = .12) over 6 months of follow-up. For the outcome of bacteriuria with symptoms, sensitivity of urinary diagnostic tests such as bacteria and pyuria on microscopic analysis, and leukocyte esterase on dipstick testing, ranged from 79 to 93%. Negative predictive values of these tests approached 100%. CONCLUSIONS: Bacteriuria was a very common event, occurring in almost one-fifth of all urine samples and one-third of all subjects during 6 months of follow-up. Month-by month follow-up indicates that the natural history of bacteriuria is marked by frequent spontaneous alternation between positive and negative events. The high negative predictive value of many simple diagnostic tests commonly used for urinary tract disease suggests that they can quickly and cost-effectively rule out bacteriuria in the older female patient. PMID- 7775719 TI - Factors influencing users' return home on discharge from a geriatric intermediate care facility in Japan. AB - OBJECTIVES: To determine the factors that influence users' destinations on discharge from Geriatric Intermediate Care Facilities (GICFs), which were established in Japan in 1987 to help hospitalized older people return home. DESIGN: Retrospective chart review. SETTING: A 94-bed GICF attached to Saku Central Hospital in Japan. SUBJECTS: Charts of all users (N = 437) aged 65 years and older, discharged from the GICF between July 1987 and February 1991, were reviewed. MEASUREMENTS: The independent variables, obtained from users' admission records, were age, sex, place of residence before admission, length of stay, intellectual impairment (assessed by Karasawa's diagnostic criteria for senile dementia), ability to perform activities of daily living (ADLs), and living arrangement of users in the GICF. The dependent variable was destination after discharge from the GICF. MAIN RESULTS: Multiple logistic regression analyses revealed that, compared with users who were able to successfully return home, users with little ability to perform ADLs, male users, and those admitted from other institutions were more likely to be hospitalized. Such analyses also revealed that users who came from institutions, had low ability to perform ADLs, and lived alone were more likely to be institutionalized in nursing homes. CONCLUSIONS: Evaluating a user's physical, mental, and socioeconomic conditions at an early stage of admission to a GICF may allow us to predict whether the user can be successfully discharged to his or her home or will have to remain in the GICF for an extended period. PMID- 7775720 TI - Age-related differences in the utilization of therapies post acute myocardial infarction. AB - OBJECTIVE: To describe the effect of age on the care of patients hospitalized with acute myocardial infarction (MI). DESIGN: Retrospective chart review of all cases with a primary or secondary discharge diagnosis of acute MI. SETTING: Two large community hospitals in Milwaukee, Wisconsin, from July 1, 1990 to June 30, 1991. PATIENTS: There were 771 charts reviewed, of which, 149 cases were aged 54 years or younger, 203 were 55 to 64 years, 224 were 65 to 74 years, and 195 were aged 75 years or older. MEASUREMENTS: Hospital charts were examined for use of diagnostic and therapeutic interventions, including medications and procedures, as well as length of stay and in-hospital mortality. RESULTS: Older patients were more likely to be female (18%, 20%, 38%, and 56% for the four age groups, respectively, P < .001 chi-square for linear trend), more likely to present with congestive heart failure (31%, 39%, 51%, and 72%, P < .001), and had a higher in hospital mortality rate (5%, 7%, 10%, and 18%, P < .001). Older patients had a longer length of stay in the hospital. The use of cardiac catheterization in these post-MI patients was high and did not decrease until after age 75 (85%, 88%, 88%, and 47%, P < .001). The percentage of patients receiving balloon angioplasty decreased with age (51%, 51%, 43%, and 20%, P < .001), whereas the percentage of patients receiving myocardial revascularization did not significantly differ with age (15%, 22%, 25%, and 19%, P = .46). Aspirin was less likely to be prescribed to older patients at discharge (79%, 82%, 70%, and 62%, P < .001). CONCLUSION: A surprisingly high percentage of those older than age 65 received invasive tests and interventions. This high utilization rate coexists with our continued ignorance about the efficacy of these tests and interventions in older adults. PMID- 7775721 TI - Age as a determinant of cardiopulmonary resuscitation outcome in the coronary care unit. AB - OBJECTIVE: To determine whether age is associated with the outcome of cardiopulmonary resuscitation (CPR) in the coronary care unit (CCU). DESIGN: Retrospective chart review. SETTING: The coronary care units of two Canadian tertiary care teaching hospitals. PATIENTS: Two hundred sixty-four coronary care unit patients undergoing cardiopulmonary resuscitation between January 1, 1985 and June 30, 1992. RESULTS: There was no significant difference in survival to discharge after CPR between patients less than 70 years of age (17.0%) and patients 70 years of age and older (17.2%) (odds ratio = 0.99; 95% confidence interval = 0.46, 1.80). Patients 70 years of age and older who survived to discharge after CPR had significantly greater lengths of stay (28.1 vs 19.3 days, P = .008). CONCLUSIONS: Age was not associated with a difference in survival to discharge after CPR in the CCU, although a clinically significant difference could not be excluded because of limited power. PMID- 7775722 TI - Posturography and balance problems in older people. AB - OBJECTIVE: To determine which measurements and test conditions on posturography are most useful for identifying balance problems in older people. SUBJECTS: Two samples of 70 community-dwelling older subjects (> 75 years). One group (controls) considered their balance normal for their age, and the other (patients) complained of imbalance. MEASUREMENTS: Velocity of sway on static (with and without foam) and dynamic posturography, Tinetti gait and balance score, self-reported fear of falling, and number and circumstances of falls. RESULTS: Mean sway velocity was significantly increased in patients compared with controls. The greatest difference between patients and controls occurred with measures of anterior-posterior sway velocity during angular tilt of the platform. Sway velocity was not significantly increased in patients or controls who reported falls compared with those who did not report falls. Even when comparing those who fell as a result of loss of balance with those who fell because of trips or slips, there was no significant difference in sway velocity. By contrast, those who reported fear of falling (patients and controls) had significantly increased sway velocity compared with those who did not report fear of falling. CONCLUSION: On average, velocity of sway (particularly in the anterior-posterior direction) is higher in older subjects who complain of imbalance compared with age-matched controls, and the difference is greater with dynamic posturography than with static posturography. However, the posturography data provided little information about the cause of the imbalance and did not correlate with the frequency of reported falls. PMID- 7775724 TI - Contractures and loss of function in patients with Alzheimer's disease. AB - OBJECTIVE: To investigate the prevalence of contractures in patients with Alzheimer's disease and to assess possible associations between contractures and cognitive and functional decline in Alzheimer's disease. DESIGN: Case series. SETTING: Subjects from an outpatient, university-based, dementia research center, followed, when necessary, into residential home and nursing home settings. PATIENTS: A consecutive sample of 161 patients (48 men, 113 women; mean age 75.3 +/- 8.6 years) with a clinical diagnosis of probable Alzheimer's disease and with deficits in basic activities of daily living or more severe functional impairment. MAIN OUTCOME MEASURES: For cognition, the Mini-Mental State Examination (MMSE); for functioning, the Functional Assessment Staging Scale (FAST); contracture is defined as a decrease of 50% or more of the normal passive range of motion of the joint. RESULTS: Prevalence of contractures was correlated highly with degree of functional impairment (r = .70, P < .001). More than three quarters of patients who had lost the ability to walk manifested contractures; however, contractures were found in fewer than 11% of all ambulatory patients examined. When present, contractures involved more than one extremity in 97% of cases and involved all four extremities in more than two-thirds of patients. CONCLUSION: Joint contractures are very common in the severe stages of Alzheimer's disease. More than a quarter of a million institutionalized residents in US nursing homes are likely to be afflicted by this potentially painful and disfiguring condition. Possible pathophysiology and contributing factors and possible means of intervention for this major source of disability are discussed. PMID- 7775723 TI - Older community-dwelling adults' attitudes toward and practices of health promotion and advance planning activities. AB - OBJECTIVE: To describe the attitudes toward and practice of health prevention and advance planning measures by a group of community-dwelling older adults and to examine the effect of age on these practices. DESIGN: A descriptive study performed by mail survey. PARTICIPANTS: Members of a research registry who were 65 years of age or older. MEASUREMENTS: By means of a written questionnaire, we asked about knowledge of various health prevention and advance planning topics, including exercise, cholesterol screening, rectal examination, influenza vaccination, sigmoidoscopy, mammography, prostate cancer screening, organ donation, autopsy, health care proxy, and advance directives. Of those who knew about the topic, we asked if the respondent had discussed it with a physician, who initiated the conversation, and if the respondent participated in the activity. We also asked how important the topic was to the respondent. RESULTS: We received 598 completed surveys, a response rate of 83%. Respondents had a mean age of 74 years, were predominately white (96%), and were well educated, with 44% having completed college. The respondents were all knowledgeable about the topics, and, with the exception of sigmoidoscopy, organ donation, and autopsy, more than 70% thought these topics were important. In the case of health screening and prevention activities, a large percentage of respondents reported having discussed the topic with a physician, and a slightly smaller percentage reported regular participation. In the case of health care proxies and advance directives, however, only about one-half of those who had made these arrangements said they had discussed them with a physician. When discussion did occur, it was much more likely to have been initiated by the respondent. Controlling for level of education, age was inversely associated with the likelihood of a woman reporting she had undergone mammography (P < .05). Age, however, was not associated with decreased frequency of undergoing other screening tests. CONCLUSIONS: Among a group of well educated older adults, reported interest in and compliance with health screening, health promotion, and advance planning activities were high. However, sigmoidoscopy, a relatively more invasive procedure that is generally recommended as a screening tool, is reported less likely to be practiced than prostate cancer screening, a less invasive procedure without such recommendation. Older adults state they are pursuing health care proxies and advance directives, often without the involvement of their physicians. Of the screening tests about which we asked, age was associated only with less frequent practice of mammography. PMID- 7775725 TI - A low, 'normal' score on the Mini-Mental State Examination predicts development of dementia after three years. AB - OBJECTIVES: To study whether a low, "normal" sumscore (i.e., 24 or higher) on the Mini-Mental Status Examination (MMSE) near the cutpoint usually employed for identifying persons with cognitive impairment predicts later development of dementia. DESIGN: A prospective study of a random sample of nondemented persons aged 75 years and older, according to DSM-III criteria, with follow-ups after 3 and 6 years. PARTICIPANTS: The subjects were 215 persons living at home, mean age 81 years, 81% women. Their mean MMSE sumscore at the start of the study (T0) was 27.9 (range 24-30). MAIN RESULTS: A low MMSE sumscore at T0 was identified as a statistically strongly significant predictor of dementia after 3 years (P < .001), when more than 40% of those with a sumscore of 24 or 25 at T0 had become demented. A similar, although weaker and statistically nonsignificant, trend was observed for the risk after 6 years in relation to MMSE scoring at baseline. CONCLUSION: Persons with a sumscore of 24 or 25 and classified as not suffering from dementia according to the DSM-III criteria are at high risk of developing dementia within 3 years. PMID- 7775726 TI - Effect of hormone replacement therapy for menopause on the mechanical properties of skin. AB - OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) for menopause on the mechanical properties of the skin in healthy women. DESIGN: A group of 114 women, including 43 nonmenopausal controls, 46 menopausal women with HRT and 25 menopausal women without HRT, participated in the study. Mechanical properties of the skin were measured on the volar forearm using a computerized suction device. SETTING: University medical center. Research laboratory in bioengineering and biometrology. RESULTS: Computerized measurements of skin deformability and viscoelasticity revealed differences between the three groups of women. A steep increase in skin extensibility was evidenced during the perimenopause in untreated women. HRT appeared to limit the age-related increase in cutaneous extensibility, thereby exerting a preventive effect on skin slackness. No effect of HRT was found on other parameters of skin viscoelasticity. CONCLUSION: HRT has a beneficial effect on some mechanical properties of skin and thus may slow the progress of intrinsic cutaneous aging. PMID- 7775727 TI - Mechanisms of constipation in older persons and effects of fiber compared with placebo. AB - OBJECTIVE: To investigate the mechanisms of constipation and the effect of fiber supplementation on physiology, mechanisms, stool parameters, and colonic transit times in a group of constipated older patients. DESIGN: Single-blind, randomized, placebo-controlled fiber intervention with crossover. SETTING: A university-based outpatient center. PATIENTS: Ten community-living older men and women, healthy except for chronic constipation. INTERVENTIONS: Patients were given either 24 g psyllium fiber or placebo fiber daily for 1 month, then crossed over to the other arm for an additional month. Structured testing, including total gut transit time and rectal and colonic manometry, was performed at the end of each intervention month. Patients recorded stool frequency, consistency, and weights daily. RESULTS: The predominant mechanism for constipation in these patients was outlet delay caused by pelvic dyssynergia. Fiber decreased total gut transit time from 53.9 hours (placebo condition) to 30.0 hours (P < .05). Stool weights and consistency were not significantly improved by fiber, though there was a trend toward an increase in stool frequency (1.3 vs 0.8 bowel movements per day.) Pelvic floor dyssynergia was not remedied by fiber, even when constipation was clinically improved. CONCLUSIONS: Fiber supplementation appeared to benefit constipated older patients clinically, and it improved colonic transit time, but it did not rectify the most frequent underlying abnormality, pelvic floor dyssynergia. PMID- 7775728 TI - Thyroid autoantibodies in hospitalized chronic geriatric patients: prevalence, effects of age, nonthyroidal clinical state, and thyroid function. AB - OBJECTIVE: To investigate the effect of age, clinical condition, and thyroid function on the prevalence of thyroid autoantibody positivity in hospitalized chronic geriatric patients. DESIGN: A screening study of hospitalized chronic geriatric patients. PARTICIPANTS: 249 non-selected, hospitalized, chronic geriatric patients more than 60 years of age and 81 20 to 40-year-old healthy persons. MEASUREMENTS: Thyrotropin (TSH); thyroxine (T4) and free thyroxine (FT4); and triiodothyronine (T3), thyroglobulin (Tg), antibodies against thyroid peroxidase (AbTPO) and antibodies against thyroglobulin (AbTg) estimation in a screening study. RESULTS: AbTPO positivity (AbTPO+) was found more often than AbTg positivity (AbTg+) (15.3% vs 9.2%, P = .04), one being positive (Ab+) in 19.3%. The occurrence was higher in females than males (Ab+:27.1% vs 7.1%, P < .001; AbTPO+:21.9% vs 5.1%, P < .001; AbTg+:13.2% vs 3.1%, P = .0052). Among the Ab+ patients, AbTPO was more often positive than AbTg (40/48 vs 21/48, P < .001). The sensitivity, specificity, and positive predictive value of Ab positivity to detect a thyroid disorder were 0.35, 0.85 and 0.38, respectively. Within the population of euthyroid geriatric patients, the occurrence of AbTg+ (chi 2(2) = 8.65, P = .013) and Ab+ (chi 2(2) = 8.02, P = .018) correlated positively with the age of the patients, and there was also a female predominance (AbTPO+ 18% vs 3.7% in the males; AbTg+ 13% vs 2.4%; Ab+ 25.8% vs 6.1%). When compared with 20 to 40-year-old subjects, only the euthyroid > or = 80-year-old patients showed a significantly higher occurrence of Ab+ (26.2% vs 9.9% chi 2(1) = 5.64, P = .017). In the euthyroid > or = 80-year-old females, AbTPO+ was 25%, AbTg:22.2%, and Ab+: 36.1%!. The nonthyroidal clinical state of the euthyroid patients did not correlate with the antibody prevalence. CONCLUSIONS: In hospitalized chronic geriatric patients, AbTg and especially AbTPO positivity is frequent, even in euthyroid patients without goiter. This aspecific Ab positivity in the euthyroid state correlates to the age, but not to the severity of the nonthyroidal clinical condition of the patients and explains why the Ab positivity is not predictive enough for thyroid dysfunction in this subpopulation. Thus, in hospitalized chronic geriatric patients the AbTg and AbTPO titers should be examined only in cases where thyroid screening (TSH) reveals abnormal results. PMID- 7775729 TI - The reliability and validity of the Geriatric Depression Rating Scale administered by telephone. AB - OBJECTIVE: To evaluate prospectively the reliability and validity of the Geriatric Depression Scale administered by telephone (T-GDS) in patients undergoing outpatient comprehensive geriatric assessment. SUBJECTS: A total of 101 geriatric patients were evaluated in a 1-year period at the outpatient Geriatric Assessment Center of the University of Nebraska Medical Center. METHODS: The 30-item GDS was completed by all patients on three occasions: by telephone several days before their assessment, face-to-face during their assessment visit, and several days later, again by phone. During their assessment, all patients were evaluated by one of three geriatric psychiatrists who were blind to all GDS results. The test-retest reliability of the T-GDS was measured by comparing the results of the two phone interviews. The construct validity of the T-GDS was estimated by comparing the results of the initial T-GDS to the GDS obtained during the comprehensive assessment. The criterion validity of the T-GDS was estimated by comparing the results of the T-GDS with the clinical diagnosis of depression assigned by the psychiatrists. RESULTS: The individual items of the initial T-GDS showed substantial concordance with the second T-GDS (kappa range 0.35-0.75, mean = 0.52), and with the assessment GDS (kappa range 0.29-0.75, mean = 0.52). One item showed evidence of bias when comparing the two T-GDSs, and two items when comparing the initial T-GDS to the GDS done during the assessment. The mean number of symptomatic responses was not significantly different for the T-GDS versus assessment administration but did decline slightly when comparing the two T-GDSs. ROC curve analyses showed good agreement between the clinical diagnosis and the T-GDS. CONCLUSION: The GDS appears to maintain its reliability and validity when administered via telephone and thus may be useful for a variety of epidemiological and clinical purposes. PMID- 7775730 TI - Concurrent validity of administering the Geriatric Depression Scale and the physical functioning dimension of the SIP by telephone. PMID- 7775731 TI - Reliability of screening for sensory impairment in depressed versus nondepressed older adults. PMID- 7775733 TI - Health care reform and the care of older adults. PMID- 7775732 TI - Are acting and omitting morally equivalent? A reappraisal. PMID- 7775734 TI - The healthcare revolution: change and impact on geriatric medicine. PMID- 7775735 TI - Report on public policy: whatever happened to comprehensive health care reform? PMID- 7775737 TI - Withdrawing versus withholding therapy: still a pernicious distinction. PMID- 7775736 TI - International common denominators in geriatric rehabilitation and long-term care. PMID- 7775739 TI - Letter from Toronto. PMID- 7775740 TI - Pneumoperitoneum in an older patient. PMID- 7775738 TI - Healthcare reform: benefits or hazards for the frail and their doctors. PMID- 7775741 TI - Falls Handicap Inventory (FHI)--an instrument to measure handicaps associated with repeated falls. PMID- 7775742 TI - The evolution of nursing homes. PMID- 7775743 TI - Postprandial hypotension. PMID- 7775744 TI - Physician assessment of patient competence. PMID- 7775745 TI - Physician assessment of patient competence. PMID- 7775746 TI - Endoscopic carpal tunnel release: a prospective study of complications and surgical experience. AB - A 63-center prospective study of endoscopic carpal tunnel release using the Agee Carpal Tunnel Release System was conducted in 1049 procedures in 988 patients. Prior experience with endoscopic release varied significantly among surgeon participants. Surgeons evaluated the newly redesigned system for blade visibility, blade height, and mechanical function. Data on patient complications were collected at the time of surgery and 3-4 weeks postoperative. The results indicated minimal complications and no confirmed injuries to vessels or nerves; the symptoms from one possible digital nerve injury eventually resolved completely. Surgeons were able to observe the point of entry of the blade into the transverse carpal ligament in 97.5% of procedures. Introduction of the blade assembly into the carpal tunnel was rated easy or adequate in 90.6% of procedures, and blade height was rated adequate in 97.4% of procedures. PMID- 7775747 TI - Biomechanical changes after carpal tunnel release: a cadaveric model for comparing open, endoscopic, and step-cut lengthening techniques. AB - We used a previously described cadaveric model for evaluating changes in flexor tendon biomechanics after open carpal tunnel release to evaluate endoscopic and step-cut lengthening techniques. A 26% and 18% increase in tendon excursion consumed by wrist motion was demonstrated for flexor digitorum profundus and flexor digitorum superficialis tendons respectively after open transection of the transverse carpal ligament. A 21% and 15% increase in tendon excursion was demonstrated after endoscopic carpal tunnel release and a 21% and 16% increase after step-cut lengthening of the transverse carpal ligament. Increased excursion was noted after 20-30 degrees of wrist flexion as tendon bowstringing occurred. Although division of the transverse carpal ligament by all methods resulted in a significant increase in tendon excursion, the differences between methods of carpal tunnel release were not significant. This cadaveric study evaluates one potential cause for weakness after carpal tunnel release, palmar displacement of the flexor tendons, which results in increased flexor tendon excursion consumed by wrist motion. PMID- 7775748 TI - Externally applied forces to the palm increase carpal tunnel pressure. AB - Change in carpal tunnel pressures that result from externally applied forces to the palm of the hand were assessed in five cadaveric specimens. MIKRO-TIP transducers were percutaneously placed into the carpal tunnel at the level of the hook of the hamate. A 1 kg force was applied to the palm of the hand in 16 separate locations. Significant elevations in carpal tunnel pressure were observed for external forces applied over the flexor retinaculum (103 mm Hg) and also for the hypothenar (37 mm Hg) and thenar (75 mm Hg) areas adjacent to the distal aspect of the carpal tunnel. These data demonstrate that the application of external forces on the palm of cadaver hands increases carpal tunnel pressure and the magnitude of the pressure change in the carpal tunnel depends on the location of the applied force. PMID- 7775749 TI - Effect of lumbrical muscle incursion within the carpal tunnel on carpal tunnel pressure: a cadaveric study. AB - Lumbrical muscle incursion within the carpal tunnel has been implicated as a possible cause of carpal tunnel syndrome. During finger flexion, surgeons have observed the presence of lumbrical muscles in the carpal tunnel. However, the significance of this incursion has not been evaluated. To evaluate the effect of lumbrical muscle incursion within the carpal tunnel as a cause of carpal tunnel syndrome, carpal canal pressures were measured in cadaver hands at the level of the hamate hook for four finger positions: (1) 100% finger flexion; (2) 75% finger flexion; (3) 50% finger flexion; and (4) full extension. After measuring carpal tunnel pressures for each position, the lumbrical muscles were excised and the pressures were again recorded. A progressive increase in carpal tunnel pressure was noted for each degree of finger flexion in the group with intact lumbricals. This is in sharp contrast to a relatively stable carpal tunnel pressure during finger flexion for the group without lumbrical muscles. Two-way repeated measures analysis of variance revealed a significant difference in carpal tunnel pressure for both variables, lumbrical muscles and finger position. One-way repeated measures analysis of variance for carpal tunnel pressures demonstrated that the effect of finger position was significant for the group with intact lumbricals but not for the group with lumbricals removed. We conclude that lumbrical muscle incursion into the carpal tunnel can result in elevation of carpal tunnel pressure in cadaver hands and could be a variable in the cause of work-related carpal tunnel syndrome. PMID- 7775751 TI - Neurologic and ischemic complications of upper extremity vascular access for dialysis. AB - This study reviews the clinical course of 22 patients with chronic renal failure on hemodialysis with ischemic or neurologic problems in the upper extremity distal to an arteriovenous fistula. Two distinct presentations were observed. Twelve patients developed significant motor and/or sensory impairment immediately following surgical construction of the fistula. Ten patients presented with upper extremity ischemia, established or impending tissue loss, or nonhealing wounds distal to a dialysis fistula. Seventeen of the 22 patients were diabetic. Nerve conduction studies, noninvasive vascular studies, and arteriography were used to confirm the diagnosis. Sixteen of the 22 patients had ligation or revision of the fistula. Five patients underwent amputations at the metacarpal or phalangeal level, and one patient underwent below-elbow amputation. PMID- 7775752 TI - Hemodynamic variations between end-to-side and end-organ flap systems. AB - This study aimed to evaluate microcirculatory differences between anatomic arrangements of the intact side flow and the end flow systems. The cremaster muscle tube-flap model was employed. Fifty male Sprague-Dawley rats were studied in two experimental groups of 25 animals each. The end-to-side vascular system was compared with end-organ flaps during acute (6 hours) and chronic (1, 3, 7, and 14 days) observation periods. Standard microcirculatory measurements were taken in all groups including vessel diameters, red blood cell velocities, and capillary densities. End-to-side flaps presented with stable flow hemodynamics over a 14-day period. In end-organ flaps we found acute venous congestion, alterations in arterial and venous flow velocities, and a significant decline in capillary perfusion. PMID- 7775750 TI - Pressure dynamics of the carpal tunnel and flexor compartment of the forearm. AB - Although carpal tunnel pressures have been observed to increase as a result of repetitive flexion and extension of the wrist, and forearm compartment pressures have been shown to rise during and after muscle activity, the relationship between those two observations has not been studied. The flexor compartments of five cadavers were perfused with saline to determine whether elevated pressure in the flexor compartment of the forearm is transmitted to the carpal tunnel. The pressure in the carpal tunnel after the infusion was significantly different from the pressure in the flexor compartment of the forearm. Furthermore, pressures recorded in the carpal tunnel at the conclusion of the study were not statistically different from the preinfusion pressures. While the carpal tunnel may appear to be an open compartment anatomically, it functions as a relatively closed compartment with respect to transfer of pressure from the flexor compartment of the forearm under conditions that mimic elevated tissue pressure. PMID- 7775753 TI - Toe-to-finger transfer combined with wrap-around flap: a new technique for four finger amputation. AB - A surgical technique for reconstruction of four-finger amputation, toe-to-finger transfer combined with wrap-around flap procedure, is described. Opposable ulnar fingers, reconstructed using the second and third toe, provide sufficient grip function. The long finger, reconstructed with the wrap-around flap using the lateral aspect of the great toe, provides pinch function. Improving the hand function is worthwhile despite morbidity from losing two toes. PMID- 7775754 TI - Arborization of the distal posterior interosseous nerve. AB - The distal posterior interosseous nerve was dissected in 41 cadaveric specimens. Intraarticular branches were tagged with radioopaque markers and verified by fluoroscopy. The nerve averaged 1.3 mm in diameter and was located on the radial side of the fourth dorsal compartment encased in thickened fascia. Six of the specimens had a branch to the distal radioulnar joint, which originated 5 cm proximal to the joint. Distally, the nerve coursed with terminal branches of the interosseous artery. Innervations were categorized according to level: radiocarpal, midcarpal, and terminal. Fourteen had innervations to all three levels, and there were radiocarpal branches in 27 specimens, midcarpal branches in 35, and terminal branches in 29. Varying combinations of innervations were seen. PMID- 7775756 TI - Difference in sensibility between the dominant and nondominant index finger as tested using the Semmes-Weinstein monofilaments pressure aesthesiometer. AB - In 130 active subjects aged 7 to 76 years, sensibility of both index fingers were tested using Semmes-Weinstein monofilaments. Subsequently, subjects were asked to indicate their dominant side. The gathered data was analysed statistically to try and find a possible difference in sensibility between the dominant and nondominant side. No difference was found in the majority of our series (76). The index at the nondominant side was found to have superior sensibility in 35 out of 130 subjects, while the reverse was true in the remaining subjects (19). In case there is a difference in sensibility between the two hands, the less sensitive side shows 'normal' distribution of light touch thresholds, whereas at the more sensitive side these thresholds usually scored one nylon rod marker lower. PMID- 7775757 TI - Neuroendocrine carcinoma of the finger: a case report. PMID- 7775758 TI - Hypertrophic neuropathy presenting with ulnar nerve compression: a case report. PMID- 7775755 TI - Subjective outcome following surgical management of upper extremity neuromas. AB - Our study used a telephone survey to evaluate long-term subjective outcome of 70 patients with 112 upper extremity neuromas treated surgically. The mean postinjury time before surgery was 9 years. The mean postsurgical followup was 5 years. Fifty-one of the patients were involved with workers' compensation (WC). Forty-five patients reported good relief of pain. Preoperatively, 46 patients were unemployed because of pain; following surgery 18 of these patients returned to work. Of the 54 patients taking analgesic medication preoperatively, 19 reported less and 10 reported no postoperative analgesic use. No significant difference was found in gender, postinjury time, postsurgical followup time, number of previous surgeries for pain relief, or site of nerve injury between patients who reported improvement versus no symptomatic improvement. Poor subjective outcome occurred in patients (p < .03), with 16 out of 19 of those not involved with WC reporting good pain relief as compared to 29 out of 51 of WC patients. PMID- 7775759 TI - Scaphoid nonunion: treatment by open reduction, bone graft, and staple fixation. AB - Thirty-eight scaphoid nonunions were treated by iliac crest bone grafting and staple fixation. A distractor was inserted through an anterior incision and the scaphoid was distracted to restore its original length. The nonunion was then grafted and held with a staple. Consolidation was achieved in 36 cases despite 6 cases of partial avascular necrosis. Pain at the graft site, which was usually transient, was the only complication. Wrist extension was significantly improved. The main indication for this procedure is pseudarthrosis of the middle third of the scaphoid. PMID- 7775760 TI - Refracture of a proximal pole scaphoid fracture: a case report. PMID- 7775761 TI - Scaphoid nonunion in a child: a case report. PMID- 7775762 TI - Type III-A hypoplastic thumb. AB - Thirteen type III-A hypoplastic thumbs were reviewed. The abnormalities included those found in type II hypoplasia (narrow thumb-index web space, hypoplastic thenar muscles, unstable metacarpophalangeal joint, as well as extrinsic tendon abnormalities); all had stable carpometacarpal joints. They are differentiated from type III-B hypoplastic thumbs, which have an unstable carpometacarpal joint due to a deficient base of the metacarpal. The extrinsic tendon abnormalities included absent extensor pollicis longus tendon, absent or aberrant flexor pollicis longus tendon, and a tendon interconnection between the flexor pollicis longus and extensor aponeurosis. Twelve of the thumbs had surgical reconstruction. None was treated with ablation and index pollicization. PMID- 7775763 TI - Flexor tenolysis in children. AB - This study aimed to determine whether there is an age below which flexor tenolysis may not be beneficial and whether there is any detriment to waiting for a more appropriate age. In this study, patients in their first decade had minimal improvement in their active flexion after flexor tenolysis. Six patients were tenolysed more than 1 year after their original operation and none appeared to have been compromised by the prolonged interval between injury repair and tenolysis. Significant improvement in active flexion after tenolysis can be confidently expected only in children over 11 years old. PMID- 7775764 TI - Correction of an angular deformity of the thumb in a juvenile by epiphyseal distraction. PMID- 7775765 TI - Biomechanical and clinical evaluation of the epitenon-first technique of flexor tendon repair. AB - Thirteen matched pairs of canine flexor tendons were repaired using both the Epitenon-first and the modified Kessler with an epitendinous running suture. These were then tested to failure with a longitudinal force in an Instron test machine. Human cadaver flexor digitorum profundus tendons were used to determine the cross sectional area of the tendon that is displaced by suture material of the Kessler repair and Epitenon-first core suture. Results of biomechanical testing revealed the epitenon-first technique to be 22% stronger than the modified Kessler technique. Comparison of tendon repair cross sectional contact areas by digital scanning of surface photomicrographs demonstrated 20% of the surface area of the repair is occupied by the knot of the modified Kessler technique, while the core suture of the epitenon-first repair consumed only 2.6% of the cross sectional area. These findings correlate with our clinical results of 26 zone II flexor tendon repairs in 18 patients repaired with the epitenon first technique over a 4-year period. Of these, there has been one rupture and no repeat operations for lysis of adhesions. PMID- 7775766 TI - Augmented Becker versus modified Kessler tenorrhaphy in monkeys: dynamic mechanical analysis. AB - The strength and gliding efficiency of an augmented Becker and Kessler tendon repair techniques were compared in fresh cadaver macaque monkey hands. Gliding efficiency was determined by comparing tendon work and load measurements made during tendon excursion to full fist with the same measurements made after tendon repair. Repair strength was then determined by tendon distraction to complete repair rupture. Data were gathered by computer controlled tensiometer and analyzed by factorial and repeated measures ANOVA. The augmented Becker repairs were significantly stronger than Kessler repairs. Repaired tendons required more load and work to bring the fingers into full fist; both repair types resulted in gliding efficiencies of 30% compared to intact controls. The augmented Becker repair is significantly stronger in situ than the modified Kessler and is recommended when early postoperative motion regimens are planned. PMID- 7775767 TI - Clinical management of partially lacerated digital flexor tendons: a survey [corrected] of hand surgeons. AB - A survey was taken of one thousand members of the American Society for Surgery of the Hand to determine the methods by which clinicians currently treat partial lacerations of flexor tendons. Results from 591 respondents show that most surgeons use a modified Kessler technique and begin protected mobilization within the first 48 hours. PMID- 7775768 TI - Flexor pollicis longus rupture in a trigger thumb: a case report. PMID- 7775769 TI - Endoscopic retrieval of severed flexor tendons. PMID- 7775770 TI - Safety and efficacy of percutaneous trigger finger release. AB - Twenty-five A1 pulleys in 5 fresh cadaveric hands and 13 trigger fingers in 11 patients were released percutaneously with a 19 gauge needle, as described by Eastwood et al., to determine the efficacy and safety of the technique. Over 90% of the length of each individual finger and thumb A1 pulley were successfully released in the cadaveric digits with no injuries to the A2 pulley, nerves, or vessels. Superficial abrasions were noted in four superficialis tendons. In our surgical series, complete clinical release (eradication of triggering) was achieved in each digit. In 8 of 13 digits, the A1 pulley was found to be completely divided on open exploration. In five digits, while triggering was eliminated, some of the A1 pulley remained intact. There were no complications. Because of the proximity of digital nerves, we do not perform percutaneous release in the index finger or thumb. PMID- 7775771 TI - Functional reconstruction of the shoulder with a latissimus dorsi pedicle flap and a hemiarthroplasty: a case report. PMID- 7775772 TI - Functional range of motion of the elbow. AB - One hundred normal upper extremities in 50 adults were sequentially studied in a Bledsoe brace, which limited elbow motion. The amount of flexion and extension of the elbow was serially limited by 15 degree increments. At each setting, the subjects were asked to perform 12 activities of daily living. The percentage of subjects who completed each task with the specified range of motion was determined. Overall, 49 of the subjects performed all of the tasks with extension limited at 75 degrees and flexion limited at 120 degrees. By isolating the allowable range of motion of the elbow and allowing for compensatory motions and strategies of the normal adjacent joints, the functional elbow range of motion is established as 75 degrees-120 degrees flexion. Thus, the functional status of a patient with a specific elbow range of motion can be predicted more accurately. PMID- 7775773 TI - Grip strength testing using the BTE work simulator and the Jamar dynamometer: a comparative study. Baltimore Therapeutic Equipment. AB - This study compared the results obtained from testing grip strength using the hydraulic Jamar dynamometer and the BTE Work Simulator. The grip strength of 14 adults was assessed with the Jamar at 90 degrees elbow flexion, Jamar at 45 degrees elbow flexion, and the BTE using the manufacturers recommended position. Greater strength measurements were generated with the elbow at 90 degrees rather than 45 degrees on the Jamar. The Jamar measurements at 90 degrees of elbow flexion were not significantly different from the BTE work simulator values. Intraclass correlation coefficients between the Jamar at 90 degrees and the BTE work simulator values were excellent. This study demonstrated that the results obtained from the BTE work simulator and the Jamar dynamometer are comparable. These findings validate the use of the BTE work simulator for grip strength testing. PMID- 7775774 TI - Ligamentous and tendinous support of the pisiform, anatomic and biomechanical study. AB - Twenty-five formalin preserved cadaveric wrists were dissected and the relationship of the piso-triquetral joint and its surrounding soft tissue structures were defined. An additional 4 fresh frozen wrists were examined in longitudinal and transverse sections. These anatomical studies showed the extensor retinaculum to have a complex insertion into the pisiform, flexor carpi ulnaris, fifth metacarpal, piso-metacarpal ligament, and the abductor digit minimi muscle. A capsulo-ligamentous structure on the medial aspect of the piso triquetral joint was also identified. Bio-mechanical testing was performed on 12 fresh cadaver wrists and the results were compared to the anatomical findings to determine the contribution of surrounding soft tissue structures to piso triquetral joint stability. Mechanical testing showed the soft tissues around the piso-triquetral joint to be strongest proximally and distally and weakest medially. Transection of the transverse carpal ligament resulted in increased lateral motion of the pisiform, but there was no significant decrease in stiffness. This study provides insight into the etiology of piso-triquetral joint instability and dysfunction. PMID- 7775776 TI - Extrinsic wrist ligaments in the pathomechanics of ulnar translation instability. AB - A description of the various combinations of ligament disruptions necessary for ulnar translation instability is presented based on a series of cadaver dissections and load studies. Dissections and load studies demonstrated that major ligament disruption, even to the extent that only the dorsal ulnolunate, the palmar ulnolunate or the radioscaphocapitate, and the long radiolunate ligaments were left intact, failed to result in meaningful ulnar translation of the carpus. The radioscaphocapitate ligament alone could not prevent significant ulnar translation. Palmar translation instability was evident with less ligament disruption than that needed for ulnar translation and was always evident if there was ulnar translation. These studies imply that ulnar translation represents a much more global ligament disruption and instability than previously suggested in the literature. PMID- 7775775 TI - Rotational stability of the carpus relative to the forearm. AB - To perform rotational tasks adequately, the rotational laxity between the radius and the carpus must be constrained within a certain limit. The contribution of nine individual capsuloligamentous structures to the rotational stability of the radiocarpal joint was studied using 14 fresh-frozen human cadaveric specimens. Torque-rotation curves, with sequential section of the soft-tissue structures, were used to calculate the percentage contribution of each individual structure. The primary pronation constraint was the palmar radioscaphocapitate ligament. The contributions to supination constraint were more complex; the dorsal radiotriquetral ligament was dominant, assisted by the palmar ulnolunate ligament. Structures originating from the ulna changed their major constraint contribution with forearm orientation, whereas those with a radial origin had a constant contribution independent of forearm rotation. Injury of these structures may lead to rotational instability at the radiocarpal level and should be considered when treating carpal instabilities. PMID- 7775777 TI - Treatment of acute injuries of the triangular fibrocartilage complex associated with distal radioulnar joint instability. AB - One hundred thirty patients who had an injury of the triangular fibrocartilage complex (TFCC) with distal radioulnar joint (DRU) instability were treated operatively. The TFCC injury with DRUJ instability occurred as an isolated lesion in 20. After appropriate fracture stabilization, 86 patients were treated with closed reduction of the DRUJ and radioulnar transfixation with one to two Kirschner wires with the forearm in neutral rotation. In 19 patients the avulsed ulnar styloid was internally fixed, and the DRUJ supplemented with radioulnar transfixation. In 13 patients the ulnar styloid was internally fixed. In 12 patients with radial avulsion fractures the displaced bony fragment was percutaneously fixed with a Kirschner-wire. Postoperatively all the patients were immobilized in a long arm cast in neutral rotation for 6 weeks. The results were excellent in 95%, fair in 30, and poor in 5. PMID- 7775778 TI - Lasso stabilization of the distal ulna after tumor resection: a report of two cases. AB - Two patients with complicated giant cell tumors of the distal ulna were treated by resection of 7.5 and 5.5 cm of the ulna, respectively. The proximal ulnar stump was stabilized with a lasso tendon graft, which allowed the patients to return to presurgery activities. The technique described is a modification of a tendon loop reconstruction used by Bunnell. PMID- 7775779 TI - Intra-articular impaction fractures of the phalanges. AB - Six patients with acute impacted fractures of the base of the proximal or middle phalanges were treated with open reduction and internal fixation. Two of three patients who presented with chronic injuries also underwent surgical reconstruction. Contiguous 1.5-mm sagittal computed tomographic imaging was performed on each proximal interphalangeal joint fracture; the imaging documented an average impaction of 30% of the articular surface area. Metaphyseal bone grafting was necessary to support the articular surface in three acute and both late patients. Rigid internal fixation, most frequently employing a composite wire tension band technique, allowed immediate postoperative range of motion exercises. At an average follow-up period of 21 months, all six acute patients had restoration of an excellent painless range of motion. There was no loss of articular congruency on final x-ray films. Late or conservative treatment of these injuries was uniformly less successful. PMID- 7775781 TI - Complications following AO/ASIF wrist arthrodesis. AB - Seventy-three wrist arthrodeses (71 patients) using AO/ASIF dorsal plate fixation and iliac crest bone graft were retrospectively reviewed to assess complications of this technique. There were 82 complications in 50 wrists. Nonunion of the radius to the carpus did not occur. Forty-five of the complications were related to the soft tissues; 29 were bone or articular complications. Chronic unexplained pain represented 8 of the complications. Overall, 63 of the 82 complications resolved. Nineteen wrists required additional surgery, most frequently for plate removal. Eighteen wrists were left with one or more residual difficulties after fusion. Thus, 55 of the wrist arthrodeses ultimately resulted in a stable, pain free wrist. PMID- 7775780 TI - Sesamoid arthrodesis for hyperextension of the thumb metacarpophalangeal joint. AB - Forty-two sesamoid arthrodeses performed since 1986 were reviewed. Thirty-seven cases were considered successful. Hypertension recurred in 3 of the 20 procedures performed for cerebral palsy and 1 of the 21 performed in association with basal joint arthroplasty for arthritic conditions. The single post trauma case was successful. Flexion was preserved. Prevention of hyperextension of the metacarpophalangeal joint assists in reducing metacarpal adduction in cerebral palsy and has a stabilizing effect in basal joint arthroplasty. PMID- 7775782 TI - An epidemiologic study of carpal tunnel syndrome and hand-arm vibration syndrome in relation to vibration exposure. PMID- 7775783 TI - How emergency physicians approach low back pain: choosing costly options. AB - To determine ways in which emergency physicians approach the diagnosis and treatment of the common presenting complaint of low back pain, responses of emergency physicians to a questionnaire dealing with three hypothetical patients with different types of low back pain were taken from a stratified national random sample of eight medical specialties. For severe acute (with and without sciatica) or chronic low back pain, physicians were asked which tests and consultants they would use in pursuit of the diagnosis, and which treatments and specialty referrals they would recommend in each of the three scenarios. For diagnosis in the acute cases (pain less than 1 week), up to 22% of emergency physicians recommended computed tomography (CT scan) and 36% recommended magnetic resonance imaging (MRI). Specialist consultation would be sought for 61% of the acute sciatica patients, 32% of the acute nonsciatica patients, and 47% of the chronic patients. In approaching treatment, over 75% of emergency physicians would advise bedrest for an average of 3.5 to 4.5 days. Between 16% and 40% suggested physical therapy for the acute patients. Referrals to surgical specialists (orthopedist or neurosurgeon) were highest (81%) for acute sciatica, compared with 52% for chronic low back pain, and 41% for acute nonsciatic low back pain. In conclusion, given that most cases of acute low back pain resolve with minimal intervention, diagnostic imaging, laboratory testing, and early specialist consultation favored by many emergency physicians would add little except expense to understanding its etiology. For treatment, emergency physician recommendations for bedrest were longer than necessary and, for physical therapy, of no proven benefit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775784 TI - Does the substitution of a resident for a flight nurse alter scene time? AB - The purpose of this study was to compare the performance of a nurse resident crew (N/R) to that of the usual nurse/nurse (N/N) crew in a helicopter transport service using scene time as a measure of overall teamwork. It was designed as a retrospective case control study carried out by a university-based helicopter emergency transport service. Emergency Medicine second-year residents who volunteered to be assigned to the helicopter transport service for 1 month rotations flew with an experienced flight nurse. This nurse/resident (N/R) team was compared to the usual nurse/nurse (N/N) team in scene trauma flights. The average ground time for the N/N crew (10.5 minutes, n = 43) was not significantly different from that of the N/R crew (10.3 minutes, n = 43). This study suggests that an emergency medicine resident can be incorporated into a flight crew without adversely affecting scene time. PMID- 7775785 TI - Prehospital needle aspiration and tube thoracostomy in trauma victims: a six-year experience with aeromedical crews. AB - The use of prehospital tube thoracostomy (TT) for the treatment of suspected tension pneumothorax (TPtx) in trauma patients is controversial. A study is presented that reviews a 6-year experience with the use of needle catheter aspiration (NA) and chest tubes performed in the field by air medical personnel. Prehospital flight charts and hospital records from 207 trauma patients who underwent one or both of these procedures in the field were retrospectively reviewed. The clinical indications used to determine treatment are presented for both procedures. Improvement in clinical status of patients observed by flight personnel were similar for both treatment groups (54% for NA, 61% for TT). Thirty two (38%) of the TT patients had failed NA attempts prior to chest tube placement. Average time on scene (T.O.S.) was significantly greater for the TT group (25.7 min versus 20.3 min for NA group). Fewer patients were pronounced dead on arrival (D.O.A.) with TT treatment compared to NA alone (7% versus 19%, respectively). Injury severity scores, number of hospital complications, length of stay (L.O.S.), and total hospital costs were not different between the two groups. There were no cases of lung damage or empyema formation associated with prehospital TT treatment. Overall mortality was similar for both groups. From these data, we conclude that NA is a relatively rapid intervention in the treatment of suspected TPtx in the prehospital setting; however, TT is an effective adjunct for definitive care without increasing morbidity or mortality. A better understanding of the physiology of intrapleural air masses is needed to determine the most effective decompression requirements prior to aeromedical transport. PMID- 7775786 TI - Traumatic retropharyngeal hematoma--a cause of acute airway obstruction. AB - Blunt trauma causing a retropharyngeal hematoma without an associated cervical fracture is a relatively rare occurrence. This article presents the case of a patient with airway compromise from a retropharyngeal hematoma, and discusses the diagnosis, airway management, and treatment of this condition. PMID- 7775787 TI - Traumatic bilateral carotid dissection. AB - Traumatic dissection of the carotid artery is an infrequent but serious complication of blunt cranial-cervical injury. The typical patient presents with deficits attributable to cerebral ischemia in the distribution of the affected vascular supply. Key considerations in the clinical picture are a delay in symptom presentation, normal initial computed tomography scans, and potential for concomitant cerebral or visceral injury. Because the initial clinical and diagnostic picture may be normal, it is crucial for emergency physicians to aggressively search for this injury in the presence of blunt cranial trauma. We present an unusual case of bilateral high extracranial carotid dissection secondary to blunt trauma. The pathophysiology of carotid artery trauma, treatment options, and key acute care issues are discussed. PMID- 7775788 TI - Missed slipped capital femoral epiphysis: illustrative cases and a review. AB - Slipped capital femoral epiphysis (SCFE) is a fairly common condition affecting older children and adolescents, and has the potential for long-term, crippling sequelae. Early recognition is the single most important controllable factor, but the diagnosis is often missed or delayed, resulting in progression of the slip. A SCFE should be suspected and promptly evaluated in any older child or adolescent presenting with a limp or complaints of hip, groin, thigh, or knee pain, especially if the patient is overweight. The diagnosis is usually made by anteroposterior and frog-leg lateral radiographs of the hips. Common errors at initial presentation include: not obtaining hip radiographs (due to either no hip pain or the lack of an impressive history and physical findings); misreading hip radiographs (the findings can be subtle); and lack of timely referral. Early involvement of and treatment by an orthopedic surgeon can greatly reduce the potential complications. We present three cases of SCFE that highlight common errors made at initial presentation, and a discussion that includes the differential diagnosis of an older child or adolescent with a painful limp. PMID- 7775789 TI - Magnetic resonance evaluation of brainstem dysfunction in eclampsia and the HELLP syndrome. AB - An unusual case of a 40-year-old woman with eclampsia and the HELLP syndrome associated with brainstem dysfunction is presented. The patient made a progressive neurological recovery. A follow-up magnetic resonance image (MRI) demonstrated complete resolution of the multiple foci. The MRI of the brainstem was found to correlate far more closely with neurological findings than with computed tomography (CT scan). PMID- 7775790 TI - Abdominal gestation. AB - Abdominal pregnancy is such an unusual form of ectopic gestation that the diagnosis is often missed or delayed. We report three cases, each with a different clinical presentation. A careful history and evaluation in the Emergency Department (ED), along with liberal and timely use of ultrasonography, are critical for prompt diagnosis and treatment. Features such as abdominal pain inconsistent with a previous presumptive diagnosis, or repeated ED visits, in a patient with a positive beta-HCG test, are suggestive of this diagnosis. PMID- 7775791 TI - Clozapine overdose, a case report. AB - Clozapine, an atypical antipsychotic agent with few of the extrapyramidal side effects of other antipsychotic agents, was approved for use in the United States in 1989. Because of drug-induced agranulocytosis, it is dispensed only under rigid guidelines. Overdose has been rare. Presented here is a case of clozapine overdose treated successfully with supportive care in which agranulocytosis did not develop. PMID- 7775793 TI - An introduction to disaster medicine in Europe. AB - Disaster medicine, which is based primarily on military and emergency medicine, is a young branch on the old tree of medicine. It touches on various disciplines within and outside the medical field. The subject is being taught on the academic and postacademic levels at many universities throughout Europe. The first chair in disaster medicine was established in Linkoping, Sweden; the second is now in Amsterdam, The Netherlands. Some aspects of disaster medicine specifically oriented toward Europe are presented. PMID- 7775792 TI - Comparison of three methods of gut decontamination in tricyclic antidepressant overdose. AB - The purpose of this study was to prospectively compare the effectiveness of three different gut decontamination methods in 51 patients presenting to an emergency department with tricyclic antidepressant overdose. Patients were randomized to three treatments; Group 1 received activated charcoal, Group 2 received saline lavage followed by activated charcoal, and Group 3 received activated charcoal followed by saline lavage followed by activated charcoal. Baseline characteristics of the three groups did not differ, including Glasgow Coma Scores, age, and mean tricyclic antidepressant levels. Average length of stay in admitted patients was 93.3 hours in Group 1, 107.2 hours in Group 2, and 66.7 hours in Group 3. Of those admitted to an ICU, average ICU time was 66.9 hours in Group 1, 54.1 hours in Group 2, and 34.4 hours in Group 3. Average duration of sinus tachycardia was 20.8 hours in Group 1, 30.8 hours in Group 2, and 32.2 hours in Group 3. Of those requiring mechanical ventilation, average ventilator time was 43.4 hours in Group 1, 24.1 hours in Group 2, and 17.8 hours in Group 3. No statistically significant difference could be shown with respect to the clinical endpoints noted. There were no deaths in any of the groups. All three methods of gut decontamination had similar clinical outcomes. PMID- 7775794 TI - Ligamentous injuries of the wrist. AB - Wrist injuries occur commonly. Significant wrist injuries such as perilunate dislocation and scapholunate dissociation may occur without carpal bone fracture. The emergency physician can recognize these ligamentous wrist injuries by noting abnormalities of the shapes, joint spaces, and alignments of the carpal bones. Early diagnosis allows for prompt referral and optimal outcome. PMID- 7775795 TI - Selection criteria utilized for hyperbaric oxygen treatment of carbon monoxide poisoning. AB - Medical directors of North American hyperbaric oxygen (HBO) facilities were surveyed to assess selection criteria applied for treatment of acute carbon monoxide (CO) poisoning within the hyperbaric medicine community. Responses were received from 85% of the 208 facilities in the United States and Canada. Among responders, 89 monoplace and 58 multiplace chamber facilities treat acute CO poisoning, managing a total of 2,636 patients in 1992. A significant majority of facilities treat CO-exposed patients with coma (98%), transient loss of consciousness (LOC) (77%), ischemic changes on electrocardiogram (91%), focal neurologic deficits (94%), or abnormal psychometric testing (91%), regardless of carboxyhemoglobin (COHb) level. Although 92% would use HBO for a patient presenting with headache, nausea, and COHb 40%, only 62% of facilities utilize a specified minimum COHb level as the sole criterion for HBO therapy of an asymptomatic patient. When COHb is used as an independent criterion to determine HBO treatment, the level utilized varies widely between institutions. Half of responding facilities place limits on the delay to treatment for patients with only transient LOC. Time limits are applied less often in cases with persistent neurologic deficits. While variability exists, majority opinions can be derived for many patient selection criteria regarding the use of HBO in acute CO poisoning. PMID- 7775796 TI - Retinal hemorrhage in the young child: a review of etiology, predisposed conditions, and clinical implications. AB - Retinal hemorrhage is a frequent finding in child abuse, but may also be associated with cardiopulmonary resuscitation, accidental trauma, and a variety of illnesses such as blood dyscrasias and infections. Although it is imperative that child abuse be considered in all children who present with retinal hemorrhages, whether retinal hemorrhages can be attributed to cardiopulmonary resuscitation in suspected cases of abuse poses a dilemma. The etiologies of retinal hemorrhage as well as the literature presently available to support or refute the various diagnoses are discussed. Guidelines for funduscopic examination in the Emergency Department as well as a clinical classification of retinal hemorrhage are provided. In addition, guidelines are suggested for the appropriate clinical investigations in children with retinal hemorrhages. PMID- 7775797 TI - A case of peri-lunate dislocation. PMID- 7775798 TI - Airway management for a retropharyngeal hematoma. PMID- 7775799 TI - Isolated bladder rupture after minor trauma in a patient with alcohol intoxication. PMID- 7775800 TI - "Impending death" and sertraline. PMID- 7775801 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: traumatology, Part 2. AB - This is the 31st article in a continuing series of objectives to direct emergency medicine resident experiences on off-service rotations. Neck and torso trauma accounts for a large portion of injuries, and its management is an essential part of training in emergency medicine. Due to the often life-threatening presentations of trauma victims, resident instruction may be conducted at the bedside in difficult and demanding situations. Therefore, it is essential for residents to have specific goals and objectives to guide their acquisition of knowledge required to make critical decisions for patients with major trauma. PMID- 7775802 TI - Correlation between urinalysis and intravenous pyelography in pediatric abdominal trauma. AB - Controversy exists surrounding the appropriate indications for intravenous pyelography (IVP) in assessing blunt renal injuries in children. Forty-one consecutive cases of suspected blunt renal injuries, who had an IVP performed between January 1988 and December 1990 at The Children's Hospital of Eastern Ontario, were examined by a retrospective chart review. Eighty percent of the IVPs were normal. Of the eight abnormal IVPs, four were contusions, two lacerations, and two nontraumatic abnormalities. There was no hemodynamic compromise, no requirement for surgical intervention, and no deaths in the study population. In the absence of significant hematuria (> or = 100 rbc/hpf), the probability of detecting a traumatic abnormality on IVP is low (4%). There was no correlation between the mechanism of injury and the IVP findings. We conclude that intravenous pyelography has a low yield in the absence of significant hematuria (> or = 100 rbc/hpf). PMID- 7775803 TI - Emergency department use and misuse. AB - We conducted a 14-day survey of the emergency department (ED) at a university tertiary care teaching hospital to examine appropriate and inappropriate use of the ED. The results are based on a convenience sample of 849 patients, selected to represent a 1-week period. Three categories (CAT) of patients were defined. CAT I: patients had a medical condition that could only be assessed in the ED. CAT II: patients had a medical condition that required evaluation either in the ED or elsewhere within 6 hours of triage. CAT III: patients could wait to be evaluated 6 or more hours from time of triage. Patients in CAT II were matched with outpatient facilities (OPF), based on the time of presentation, the presenting complaint, investigative tests, and treatments required. Overall, it was found that 69% of the patients were appropriate users and could have been seen only in the ED. Fifteen percent of the patients were classified as inappropriate users and should have been seen at an OPF. The remaining 15.8% represented "gray zone" cases. An interview conducted on a subset of ambulatory patients revealed the main reasons for choosing to visit the ED were lack of awareness of other facilities, perceived seriousness of condition, trust in the ED staff, or proximity of the ED. It was concluded that misusers represent a small portion of our ED caseload. PMID- 7775805 TI - Immunotherapeutic strategies targeting rheumatoid synovial T-cell receptors by DNA inoculation. AB - Immunotherapy against autoreactive T-cell receptors (TCRs) has been reported to have promise in several animal models of autoimmune diseases. Facilitated DNA inoculation has many potential advantages as a modality for development of specific immune responses. Specifically, this technology is able to deliver exogenous antigens for processing via both the endogenous pathway, with subsequent presentation by class-I major histocompatibility (MHC) antigens, and the exogenous pathway, with subsequent presentation by class-II MHC antigens. This allows for induction of both arms of the cellular immune system. These cellular immune responses may be particularly important in targeting and controlling pathogenic cell populations. The application of this technology to the treatment of human autoimmune diseases depends on the availability of readily manipulated systems for the evaluation of specific interventions. Here we report the full length cloning and expression of TCRs from rheumatoid arthritis synovial tissue. These were developed by recombinant polymerase chain reaction, cloning and retroviral transduction into a TCR-alpha/beta-negative murine T-cell hybridoma. Reconstitution of CD3 expression was confirmed by flow cytometry. Similar constructs have been developed for TCR-based immunotherapy by facilitated inoculation of DNA intramuscularly. Preliminary analysis of immune responses in mice indicates that these constructs elicit anti-TCR responses. These studies indicate the ability to reconstitute expression of potentially autoreactive human TCRs in a model system wherein specific immune responses elicited against these TCRs by various immunogens can be evaluated. PMID- 7775806 TI - DNA inoculation as a novel vaccination method against human retroviruses with rheumatic disease associations. AB - There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjogren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint. PMID- 7775804 TI - T-cell antigen receptors in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by chronic inflammation mainly in the joints. Several lines of evidence suggest that T cells are involved in the pathogenesis of the disease. RA is associated with certain HLA-DR alleles. Studies analyzing T-cell receptor transcripts in RA have found biased or preferential usage of certain V alpha and/or V beta gene segments by T cells infiltrating the synovial membrane or extravasating into the synovial fluid compared to peripheral blood. In certain patients few T-cell antigen receptor (TCR) clones dominated the infiltrating T cells, suggesting that T cells from the synovial membrane or the synovial fluid comprise oligoclonal populations of T cells. However, other studies have found a polyclonal population of T cells. In interpreting these results the phase of the disease (early vs. late RA), the source of T cells and the limitations of the methods used in these studies should be taken into consideration. However, it appears that synovial T cells comprise oligoclonal populations of T cells and that there is a bias towards particular TCR gene segments, although a specific TCR gene segment in RA has not emerged. PMID- 7775807 TI - Intracellular location of inapparently infecting Chlamydia in synovial tissue from patients with Reiter's syndrome. AB - Culture of Chlamydia trachomatis from synovial tissues/fluids from Reiter's syndrome (RS) patients frequently yields negative results. However, we have identified chlamydial RNA at that site in such patients, suggesting that viable organisms may be present. Here we define the cellular location of chlamydia within the synovium via in situ hybridization. Using a chlamydial ribosomal RNA directed probe, we show that synovial tissue from culture-negative RS patients gives strong hybridization which is often localized to a subsynovial cell layer, rather than to the synovial lining; in some cases, hybridizing cells are dispersed through the synovium. All hybridization signal is located within host cells, indicating that infectious extracellular elementary bodies are rare or absent. These data confirm the extensive intracellular presence of inapparent chlamydia in the synovia of RS patients and provide some insight into the usual culture negativity of synovial tissues for the organism. PMID- 7775808 TI - Structural properties of a subset of nephritogenic anti-DNA antibodies. AB - Structural analysis of lupus autoantibodies is beginning to provide clues to the molecular basis for antigenic specificity and pathogenicity. The present analysis indicates that multiple light and heavy chains contain residues which can facilitate DNA binding, reaffirming the notion that there are multiple ways that different amino acids combine to form an antigen-binding pocket with affinity for dsDNA and ssDNA. Furthermore, this analysis suggests that these conformations and contact residues are intrinsic to germline sequences, although amino acid changes at critical locations (somatically introduced) modulate antigen binding, and appear to influence the capacity of individual immunoglobulin to form immune deposits. Analysis of additional individual immunoglobulins with closely related V-region sequences and differing pathogenic properties will be required to resolve the contribution of specific motifs to pathogenecity. PMID- 7775810 TI - Molecular Aspects of the Rheumatic Diseases. Proceedings of the 2nd symposium. Philadelphia, Pennsylvania, June 9-10, 1994. PMID- 7775811 TI - Zyn-Linker delivery of antirheumatic agents. AB - Despite our increasing ability to manage rheumatoid arthritis through systemic medication, refractory joints require local administration of more aggressive therapy in a substantial number of patients. These studies tested whether a new class of molecules designated Zyn-Linkers could deliver and retain therapeutics in a joint. Zyn-Linkers are synthetic lipid-like molecules designed to insert into cell membranes and enhance drug delivery to cells. After intra-articular injection into the knee of NZW rabbits, Zyn-Linkers bound rapidly and homogenously to synovial lining cells. Chelating Zyn-Linkers which contained Re 186 or Y-90 were synthesized to evaluate localization and retention after intra articular injection. Initial studies using Re-186 Zyn-Linker gave excellent localization as evaluated by whole-body imaging: counts in the knee region represented > 90% of counts present in the whole body for at least 4-6 days postinjection. Similar results were obtained using a Y-90 Zyn-Linker and this agent was used for biodistribution studies due to its greater stability and ease of preparation. Efficacy and safety of Y-90 Zyn-Linker as a potential radiation synovectomy agent were estimated by extrapolation of biodistribution data to humans. A therapeutically effective dose of 8,000 cGy to synovium was calculated to require intra-articular injection of 3.4 mCi Y-90 Zyn-Linker, a value less than or equal to doses of particulate Y-90 agents used clinically in Europe. The predicted safety profile for Y-90 Zyn-Linker was excellent, with estimated doses to nontarget organs and tissues falling well within FDA-recommended safety levels for research-only radiopharmaceuticals. In addition to exhibiting desirable localization and retention properties, Zyn-Linkers may also be synthesized to release antirheumatic drugs such as methotrexate at controlled rates. This suggests substantial potential for these drug delivery molecules as chemical synovectomy agents which may be used concurrently with systemic chemotherapy to improve management of refractory joints. PMID- 7775809 TI - Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies. AB - To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig. PMID- 7775813 TI - [The relation between delivery method and prognosis for very low birth weight infants]. AB - To further understand the relationship between perinatal factors and prognosis (neonatal and infantile death and major handicaps), we retrospectively studied 128 singletons weighing less than 1,500g (very low birth weight; VLBW) infants, without maternal complications, IUGR or major congenital anomalies. The gestational age (mean +/- SD) at delivery and the birth weight (mean +/- SD) of subjects were 27.1 +/- 2.0 weeks and 1,041.1 +/- 264.1g, respectively. The results of the current study were as follows: 1) Malpresentation, low Apgar score (APS) and Respiratory distress syndrome (RDS) were observed more frequently in non-intact survivors than in intact survivors with statistical significance. Although the occurrence of fetal distress was correlated with low pH in the umbilical artery, no significant correlation was evident between the prognosis and either of the two above mentioned factors. The intact survivors had a significantly high frequency of PROM despite no correlation with signs of infection (WBC, CRP). 2) As to delivery methods in terms of prognosis, a cephalic vaginal group had the best prognosis and a breech-vaginal group had the worst, with statistical significance. A higher frequency of poor prognosis for infants was found in a malpresentation group with cesarean delivery and cervical dilation of more than 4cm. Thus, vaginal delivery is a possible option in case of cephalic VLBW infants. PMID- 7775814 TI - [Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor messenger RNA in human endometrium and endometrial carcinoma]. AB - To study the regulation of c-erbB, EFG and TGF-alpha in endometrium, we examined the expression of their mRNA in 5 normal endometrial and 5 endometrial carcinoma tissues by Northern blot and reverse transcription-polymerase chain reaction (RT PCR). By Northern blot with 10 micrograms of total RNA, c-erbB mRNA was not detected in the normal endometrium, but it was detected in 3 samples of endometrial carcinoma tissues. On the other hand RT-PCR identified c-erbB mRNA in all the normal endometrium and endometrial carcinoma tissues by amplifying cDNA derived from c-erbB mRNA. EGF mRNA was detected by RT-PCR in normal endometrium except in the early follicular phase. It was detected in all cases of endometrial carcinoma tissues. TGF-alpha mRNA was also detected in all the normal and endometrial carcinoma tissues by RT-PCR. Our study suggests that an autocrine/paracrine mechanism of EGF may regulate the endometrial cycle. Because some endometrial carcinoma tissues express the c-erbB mRNA much more than normal endometrium, disruption of the autocrine/paracrine mechanism may trigger subsequent endometrial carcinogenesis. PMID- 7775812 TI - [Changes in natural killer (NK) activity and fertility during the establishment of experimental endometriosis in the rat]. AB - We examined the effect of experimental endometriosis (EE) on natural killer (NK) activities and fertilizability in the rat. EE was induced by autotransplantation of an endometrial fragment to the peritoneal wall. As a sham, abdominal fat tissue was implanted in the same way. NK activities of spleen cells were measured by means of a 4-hr 51Cr-release assay. RESULTS: (1) NK activities were significantly lower in EE than those in the sham (p < 0.001). (2) NK activity was recovered by surgical excision of the endometrial implant, but not increased by the administration of Danazol (100 mg/kg/day) or Buserelin (25 micrograms/kg/day) for 4 weeks. (3) The supernatant of endometriotic tissue cultures markedly suppressed NK activity. (4) The number of pups with EE was significantly smaller than in the controls (p < 0.05), but no difference between the two groups was observed in the number of oocytes in the Fallopian tube. CONCLUSION: (1) Splenic NK activity decreases at the time of the establishment of EE. (2) NK activity recovers after the removal of the implanted tissue. (3) Danazol and Buserelin have no effect on the NK activity in EE. (4) EE reveals some adverse effects on the postovulatory phase of fertility. PMID- 7775815 TI - [Estramustine phosphate, estrogen conjugated with nitrogen mustard inhibits the growth of endometrial cancer cells in vitro]. AB - Estra-1,3,5 (10)-triene-3,17-diol (17 beta)-, 3-[bis(2-chloroethyl) carbamate] (Estramustine EM) was tested for its anticancer effect on human endometrial cancer cell lines: Ishikawa and its estrogen (E) independent sub-clone EIIL (Estrogen Independent Ishikawa Line). The results showed: (1) EM inhibited growth of both cell lines in a dose dependent manner giving ID50 for Ishikawa as 12 microM and for EIIL as 65 microM. (2) The addition of EM to the culture medium caused cell detachment and death associated with a breakdown of DNA to approximately 90 base pair fragments. (3) Reverse transcription-polymerase chain reaction to examine expressions of c-erbB-2, nidogen and fas showed that EM completely abolished fas expression and resulted in a 40% decrease in nidogen expression in Ishikawa but not in EIIL. No change was seen in c-erbB-2 expression. The present data indicate that the E component of EM does not stimulate the growth of Ishikawa or EIIL. Since the growth of both cell lines was inhibited but apparently in an E receptor (ER) dependent manner, EM may be of value in an adjuvant therapy for endometrial cancer, especially an ER positive one. PMID- 7775816 TI - [Usefulness of the combined transfusion of autologous blood as pre-deposited and preoperatively diluted in gynecological surgery]. AB - To eliminate the risks involved in homologous blood transfusion in gynecological surgery, we studied the effect of the combined transfusion of autologous blood as predeposited and preoperatively diluted. Thirty-nine cases were operated on and studied. In 27 cases, a total of 695 ml/person of autoblood was taken during the 15 preoperative days. In 39 cases, an average of 1,038 ml/person of autoblood was collected at the beginning of surgery. In 37 out of 39 cases, we were able to avoid homologous blood transfusion. In the remaining two cases with homologous blood transfusion, although more than 3,000 ml of operative blood loss was observed, only about 700 ml of homologous blood was needed. We did not find any serious side effect with autoblood transfusion. These results demonstrate the usefulness of the combined transfusion of autologous blood as predeposited and preoperatively diluted in gynecological surgery. PMID- 7775818 TI - [Association of pregnancy-induced hypertension with a molecular variant of angiotensinogen gene]. PMID- 7775817 TI - [Expression of MMP-3 and TIMP-1 in the endometriosis and the influence of danazol]. PMID- 7775820 TI - [A case of pregnancy complicated with virus-associated hemophagocytic syndrome]. PMID- 7775819 TI - [Uterine artery Doppler flow velocimetry in patients with recurrent intrauterine fetal death treated with anticoagulant heparin therapy]. PMID- 7775821 TI - [A case of hydatidiform mole with coexistent normal fetus probably in twin pregnancy]. PMID- 7775822 TI - [A case of ovarian mucinous cystadenocarcinoma in a young woman after treatment of dysgerminoma on opposite side]. PMID- 7775823 TI - [Efficacy of one week-treatment of antibiotics for Chlamydia trachomatis infection]. PMID- 7775824 TI - Repair of UV-induced pyrimidine(6-4)pyrimidone photoproducts is selectively inhibited in transcriptionally active genes after heat treatment of human fibroblasts. AB - In normal human fibroblasts, repair of (6-4)PP in the active adenosine deaminase (ADA) gene occurs with similar rate in the transcribed and non-transcribed strand of the ADA gene, and removal of (6-4)PP from the active ADA gene is faster than from the inactive X-chromosomal 754 locus. Heat shock decreased the rate of repair of the active ADA gene down to the level of inactive genes, whereas the rate of repair of the inactive 754 locus was not affected. PMID- 7775825 TI - DNA damage and repair after low doses of UV-C radiation; comparable rates of repair in rodent and human cells. AB - The UV endonuclease assay for cyclobutane pyrimidine dimers in the DNA of UV-C irradiated mammalian cells has been modified by replacing alkaline sucrose sedimentation with alkaline unwinding and hydroxylapatite chromatography to determine the number of DNA breaks introduced by the endonuclease. Dimers induced by doses as low as 0.25 Jm-2 can be detected and the assay has been used to examine the capacity of human, hamster and mouse cells to remove damage inflicted by sublethal doses of UV-C. In addition, incision activity has been measured by incubating cells with DNA synthesis inhibitors after irradiation with UV-C. In rodent and human cells, given a dose of UV-C of 1 Jm-2 about half of the endonuclease-sensitive sites are lost in 5-6 h. The incision capacity of these cells corresponds well with the extent of removal of dimers. Thus, although rodent cells are normally considered to be relatively deficient in nucleotide excision repair, we find that rodent and human cells have comparable capacities to deal with low levels of UV-C-induced damage. PMID- 7775826 TI - Dependence of fluorodeoxyuridine-mediated radiosensitization on S phase progression. AB - Recent evidence casts doubt on the hypotheses that fluoropyrimidine-mediated radiosensitization is related to cytotoxicity or to cell cycle redistribution into the G1/S boundary. We hypothesized that cells that are capable of progressing into S phase in the presence of fluorodeoxyuridine may also be more susceptible to radiation-induced damage. To test this hypothesis, fluorodeoxyuridine (FdUrd)-treated HT29 human colon cancer cells were separated by centrifugal elutriation into four fractions (1-4) containing a range of cells from those at the G1/S boundary (fraction 1) to those which had progressed approximately 11% into S phase (fraction 4). We found that fraction 4 cells showed significantly greater radiosensitization than fraction 1 cells. We also compared the effects of fluorodeoxyuridine on HT29 and SW620 human colon cancer cells. We found that, in contrast with HT29 cells, SW620 cells arrested at the G1/S boundary and were minimally radiosensitized. Finally, we found that an increase in sensitivity was correlated with a decrease in the rate of repair of DNA double-strand and single-strand breaks (assessed by asymmetric field inversion gel electrophoresis and alkaline elution respectively). These findings are consistent with the hypothesis that fluorodeoxyuridine-mediated radiosensitization depends on S phase progression and a decreased ability to repair radiation-induced DNA damage. PMID- 7775827 TI - Abnormal radiosensitivity of lymphocytes from breast cancer patients with excessive normal tissue damage after radiotherapy: chromosome aberrations after low dose-rate irradiation. AB - There is a need for a simple, rapid assay for predicting normal tissue reactions in radiotherapy patients to reduce morbidity in sensitive patients and to allow dose escalation in resistant cases. Towards this goal we have investigated the gamma-ray sensitivity of lymphocytes from 16 breast cancer patients who had shown an exaggerated acute or late radiation reaction ('overreaction') of normal tissues after radiotherapy, using chromosome damage (dicentrics) as the endpoint because of its close relationship with cell killing. The use of a low dose-rate (LDR; 0.31 cGy min-1) was found to be better than a high dose-rate (170 cGy min 1) in discriminating between over-reactors and controls, as predicted (and here confirmed) from previous studies on ataxia-telangiectasia (A-T) homozygotes and heterozygotes. Five of seven patients with excessive early skin reactions (e.g. erythema, moist desquamation) showed abnormal radiosensitivity, manifested either as aberration yields above the control range after LDR exposure or as less sparing than controls. The average LDR yield for early over-reactions was significantly higher than for controls (p = 0.009) and average sparing was less (p = 0.0002). Two of 10 patients with late complications (fibrosis, telangiectasia) had LDR yields above the control range, but the average yield for late over-reactors was not significantly above that of controls. Unexpectedly, two patients (one early, one late reaction) had LDR aberration yields below the control range. Quantitatively our results are consistent with the notion that over-reacting breast cancer patients are carriers of the A-T gene. Pilot studies on controls showed that the sparing effect of LDR irradiation was increased by lowering the dose-rate to 0.13 cGy min-1 and by using micronuclei rather than metaphase damage as the endpoint. These modifications to the protocol will be used in a large-scale prospective study. PMID- 7775828 TI - Micronucleus induction in peripheral blood lymphocytes of patients under radiotherapy treatment for cervical cancer or Hodgkin's disease. AB - The genetic damage present in peripheral blood lymphocytes of patients treated with fractionated partial-body radiation therapy for cervical cancer or Hodgkin's disease was followed during treatment by means of the cytokinesis-block micronucleus assay. For each patient a dose-response relationship with respect to the number of micronuclei after in vitro irradiation of blood samples pretreatment was also determined. Comparing the individual in vivo-in vitro data, the micronucleus yields after the equivalent whole-body dose during radiotherapy were found to differ substantially from the in vitro dose-response. Contrary to the linear-quadratic dose dependence after in vitro irradiation the initial increase in the micronucleus yield during radiotherapy levelled off at elevated doses. The observed differences cannot be attributed only to the effects of interphase death and the partial irradiation of the lymphocyte pool. The correlation between the micronucleus yield and the equivalent whole-body dose for values up to 2 Gy, observed for the pooled data of the first part of the radiotherapy treatment, demonstrates the suitability of the cytokinesis-block micronucleus assay as a biological dosemeter after accidents involving partial body irradiation. PMID- 7775829 TI - Quantifying intracellular radioresponse diversity in irradiated sandwich cultures via micronucleus expression. AB - Determining the degree of diversity in therapeutic sensitivity exhibited by a tumour population is of considerable clinical importance. In addition to being a contributor to radiation resistance, diversity is the basis for variation in sensitivity over the course of treatment. To study intrapopulation diversity in radiosensitivity following gamma-irradiation (2 Gy), distributions of the number of micronuclei/binucleate cell were obtained for human cervix carcinoma sandwich populations. Cell-to-cell diversity in radioresponse (micronucleus expression) was quantified using the overdispersion index ((variance/mean)--1). As measured by this index, the radioresponse diversity of sandwich cultures sharply increased after introduction of oxygen/nutrients to the cultures, mimicking tumour reperfusion. In addition, a strong correlation was found between this measure of diversity and the extent to which the fraction of cells without micronuclei exceeds that expected from a Poisson distribution. This correlation indicates that for a diverse population there can be a significant departure of the aggregate population sensitivity (determined, for instance, by log-survival in a clonogenic assay) from that inferable from simply averaging per-cell sensitivities (reflected, e.g. by mean number of chromosome aberrations/cell). Our experimental results suggest a model attributing diversity in a population to its being a mixture of distinct subpopulations, each biologically homogeneous with respect to micronucleus expression, and each contributing an individual Poisson-distributed micronucleus response. We demonstrate how such radiodiversity may be quantified and show that reoxygenation of a microenvironmentally heterogeneous population leads to an increase in its radiobiological diversity. PMID- 7775830 TI - X-ray-induced chromosomal aberrations and cell killing in somatic and germ cells of the scid mouse. AB - To characterize further the radiosensitivity of severe combined immunodeficiency (scid) mice, the induction of micronuclei (MN) in polychromatic erythrocytes as well as cell killing and translocation induction in stem cell spermatogonia was studied. Scid mice turned out to be clearly hypersensitive for X-ray-induced cell killing of both bonemarrow cells and spermatogonial stem cells. The frequencies of recorded micronuclei in polychromatic erythrocytes were comparable with that reported for the normal mouse, whereas the recovery of translocations was extremely low in the scid mouse. The dose-response relationship for induced translocations was bell shaped with a maximum of about 0.5% around doses of 0.5 1.5 Gy X-rays. PMID- 7775831 TI - Effect of gamma-irradiation on the effector function of T lymphocytes in microbial control. AB - A chlamydial-specific T cell clone, capable of inhibiting the growth of infectious Chlamydia in vivo and in vitro, was employed to investigate the effect of gamma-irradiation on the ability of effector T cells to control infections. Clone 2.14-0 (CD4+), specific for the Chlamydia trachomatis biovar agent of mouse pneumonitis (MoPn), was irradiated with varying doses (0, 2.5, 5.0, 10.0, 20.0 and 40.0 Gy) and its biological functions and ability to inhibit the intraepithelial growth of MoPn were assessed. The results revealed that although gamma-irradiation drastically reduced the proliferative response of the clone to antigen, it did not affect the phenotype and the effector function of inhibiting chlamydial growth. The preservation of anti-chlamydial function after gamma irradiation correlated with the retention of IFN-gamma and TNF-alpha secretion in response to antigenic stimulation. We conclude that the biologic functions of T cells requiring proliferation and differentiation are more likely to be adversely affected by gamma-irradiation on the short-term, but the effector functions, possibly associated with cytokines and cytolysis, may be preserved among persisting effector T cells in an irradiated individual. PMID- 7775832 TI - Time evolution of the number of functional murine eccrine sweat glands after irradiation: a quantitative analysis of experimental data using a model of proliferative and functional organization. AB - The function of eccrine sweat glands in the beta-pad of the mouse foot after irradiation was followed over time. Graded doses of X-rays were given to the foot, either as single doses or in two equal fractions separated by a 24-h interval. A quantitative, non-invasive, functional assay was used allowing repeated evaluation of the animals. Sweat gland function was assessed once a week for the first 6 weeks, and at 8, 10, 14, 18, 28, 38 and 45 weeks after irradiation. The beta-pad of the unirradiated foot was used as a control. The function dropped to a nadir within 8-10 weeks after irradiation, whereafter it gradually recovered, reaching a stable level 20-25 weeks after irradiation. These data were analyzed using a mathematical model of proliferative and functional organization of the sweat pore. The model provides a description of the time evolution of pore function, and its basic features were as follows. The functional subunit is a single sweat pore, which will be assayed as functional provided that it contains a number of functional cells above a critical threshold. The functional cells are capable of self renewal (a so-called 'flexible' tissue), and the proportion of proliferating cells is subject to homeostatic control. Irradiation is assumed to transfer a certain fraction of the cells into a state with a limited probability of successful division. This fraction is assumed to have a linear-quadratic dependence on dose. The values of all free model parameters were optimized by a maximum-likelihood fit to the experimental data. With optimized parameter values, the initial decrease, nadir, and long-term level of tissue function estimated from the model were in close agreement with the experimental observations for all the 28 dose groups. Some of the estimated model parameters are: growth fraction 4.2 +/- 0.2%; cell cycle time, 0.95 +/- 0.04 days; number of functional cells in a single pore in the unirradiated animal, 9.9 +/- 0.5; and alpha/beta ratio, 4.3 Gy (95% confidence interval 3.1-5.0 Gy). It is concluded that the present model, despite its relative mathematical simplicity, provides a close description of the postirradiation kinetics of functional cells in the mouse sweat gland. PMID- 7775833 TI - Effect of changing weekly dose on accelerated repopulation during fractionated irradiation of mouse tongue mucosa. AB - The effect on accelerated repopulation of fractionated radiotherapy with changing weekly dose was studied in mouse oral mucosa. The basic conventional treatment protocol comprised five daily fractions per week, 3 Gy per fraction, given over 3 weeks. In dynamic treatment schedules the same total dose was delivered by giving 5 x 2, 5 x 3 and 5 x 4 Gy, or the reverse sequence. In concomitant boost experiments five additional daily doses of 1 or 2 Gy respectively were applied either during the first or last week of the conventional treatment. Graded terminating test doses were given in order to establish dose-effect curves for complete mucosal denudation. Higher initial doses consistently resulted in longer latent times between top-up irradiation and complete epithelial denudation, corresponding to significantly higher cell densities at the time of test irradiation. The top-up ED50's served as a measure of repopulation efficacy. The difference in repopulated dose between schedules with initial or terminal dose concentration was 10% for dynamic fractionation (p = 0.02) and about 7% in the 2 Gy boost protocol (p = 0.13), and no difference was observed with boost doses of 5 x 1 Gy. In conclusion, a clear though moderate increase in both cell density and residual tissue tolerance can be achieved by protocols with substantially higher doses in the first treatment week. PMID- 7775834 TI - Amelioration of radiation nephropathy by acetylsalicylic acid. AB - This investigation was carried out to assess the amelioration by two antithrombotic drugs of radiation nephropathy in mice. Mouse kidneys were given split-dose irradiation to total doses between 17 and 22 Gy. A first group of animals was given acetylsalicylic acid (ASA) in drinking water, a second received daltroban, a thromboxane A2/prostaglandin H2 receptor antagonist, and a third received normal tap water, serving as a control. Both antithrombotic drugs were started 1 week prior to the irradiation and were given throughout the whole follow-up period. Renal function was assessed every 4 weeks from 18 weeks after the start of irradiation onwards by measuring the [51Cr] EDTA retention and haematocrit. The dose of ASA (600 mg/kg/day) caused an inhibition of thromboxane A2 and prostacyclin biosynthesis to 19 +/- 10 (mean +/- SEM) and 85 +/- 22%, respectively, as assessed by the excretion of their urinary metabolites. A significant sparing effect on the renal function after irradiation was observed in the ASA-treated animals. Using the latency time to reach 4% residual plasma activity of [51Cr] EDTA, a dose-modifying factor of 1.19 was calculated. No effect was seen with daltroban (10 mg/kg/day). Histopathological analysis of the kidneys at 12 months after irradiation demonstrated a substantially lower level of damage in the ASA-treated mice compared with daltroban-treated and radiation only animals. These data indicate that long-term treatment with ASA is effective in reducing renal functional impairment after irradiation. PMID- 7775835 TI - Tumour oxygenation, radiosensitivity, and necrosis before and/or after nicotinamide, carbogen and perflubron emulsion administration. AB - Hypoxia is one of the factors involved in tumour resistance to radiotherapy. One way to improve tumour oxygenation is to use oxygen carriers such as perflubron emulsion plus carbogen or vasoactive drugs such as nicotinamide. The perflubron emulsion and carbogen act mainly on hypoxia caused by limited diffusion of oxygen; nicotinamide acts mainly on acute hypoxia. The aim was to correlate radiosensitivity and pO2 measurements (computerized pO2 histograph) after nicotinamide, perflubron emulsion and carbogen administration, and to determine the role of necrosis in this correlation. Two human tumour xenografts (HRT18, Na11 +) and one rodent tumour (EMT6) were used. Clonogenic assays and pO2 measurements were performed under similar conditions. The radiosensitization and oxygenation levels increased with all treatments. The maximal effects were found with the combination of nicotinamide (1 g/kg), perflubron emulsion and carbogen. A correlation between the radiosensitization and the pO2 measurements was found for the three cell lines with a cut-off point of 10 mmHg. The presence of necrosis could explain the low pO2 (< 2 mmHg) found even when complete radiosensitization was observed. PMID- 7775836 TI - Investigation of lung tumour induction in BALB/cJ mice following paternal X irradiation. AB - Evidence of an enhanced incidence of lung tumours (benign adenomas and adenocarcinomas) was sought in the BALB/cJ mouse following paternal germ cell X irradiation. In a series of replicate studies spanning approximately 1 year, males were exposed to single, acute X-ray doses of 0, 250 and 500 cGy. In each of the 2 consecutive weeks immediately thereafter they were placed with two females to generate progeny that were derived from irradiated post-meiotic cells (spermatozoa to late spermatids). These animals were then examined at 8 or 12 months for lung tumours. While the proportion of fertile females and mean litter size was affected by the radiation, showing a dose-dependent, dominant lethal response, and while cases of mutant offspring were detected, the paternal radiation did not affect lung tumour incidence in the offspring. The incidence did not vary significantly between germ cell stages irradiated (week of mating), sex of offspring, or radiation dose. However, significant differences between lung tumour incidence (mostly representing benign adenomas) were found between different replicates, these being high at the start of the study, declining and then rising to yet higher levels at its close. The finding that lung tumour incidence in BALB/cJ mice is not affected by paternal germ cell irradiation does not accord with Nomura's reports using other strains of mice. This, in turn, weakens biological support for a causal association between the raised incidence of childhood leukaemia and non-Hodgkin lymphoma near Sellafield and the father's recorded radiation exposure during employment by the nuclear industry. PMID- 7775837 TI - ECG of The Month. Recycling problem. Atrial tachycardia. PMID- 7775839 TI - Gastric carcinoma: recent issues in prognostic factors. AB - The prognosis of gastric carcinoma remains unfavorable despite a greater understanding of its molecular pathology. This retrospective study of primary gastric carcinomas was collected from one of the highest risk regions of China and examined for the oncogenetic expression of p53, c-erbB-2, and PCNA using immunohistochemistry and DNA contents by flow cytometry and image analysis. These products are reported to influence the tumor behavior. The p53 nuclear and c-erbB 2 membrane-bound stainings were seen in 58% and 34% of cases, respectively. A high PCNA index was found in 90% of the tumors. The p53 expression did not correlate with the histological differentiation, gross morphology, and depth of tumor invasion. Additionally, p53 and c-erbB-2 reactivity did not correlate with the proliferative index (PI) or S-phase DNA content. However, the mutant p53 expression was detected in the dysplastic cells adjacent to the tumor, suggesting a possible role of the oncogene in tumor pathogenesis. Mutant p53 expression can also be helpful in early detection of cases with dysplasia in well-differentiated adenocarcinomas. PMID- 7775840 TI - Cancer. A potentially preventable disease. AB - Current epidemiologic and carcinogenesis data are lending credence to the hypothesis that individual cancers have specific causes. Because of this, most cancers are at least potentially preventable. Primary prevention, with removal of specific etiological agents, is the best means of prevention, such as elimination of tobacco smoke. Short of knowing the specific etiology, new chemo-prevention techniques are now being studied evaluating hormonal agents, anti-inflammatory drugs, and the structural analogs of vitamin A. PMID- 7775838 TI - Otoacoustic emissions: an emerging diagnostic tool. AB - Otoacoustic emissions are acoustic signals detectable in the external auditory canal that reflect the state of health of the cochlea. Transiently-evoked otoacoustic emissions and distortion-project otoacoustic emissions are two types of otoacoustic emissions currently under investigation as well as in limited clinical use. These objective tests of cochlear function add significantly to the armamentarium currently in place for the evaluation of hearing. The clinical use of these diagnostic tools will likely increase dramatically in the coming years. The following review provides a basis for understanding the nature and clinical utility of otoacoustic emissions. PMID- 7775841 TI - Women's health. Part II: Individual, environmental and economic factors affecting adherence to recommended screening practices for breast cancer. AB - In order for cancer mortality rates to be sufficiently reduced to meet the goals set by the National Cancer Institute, it is imperative that we broaden our understanding of the factors which affect participation in preventive health practices. Early detection and diagnosis of breast cancer are associated with participation in mammography, breast self-examination, and seeking medical care. A stratified random sample of women residing in Orleans Parish (40 to 65 years of age; annual family incomes < $40,000) were surveyed by telephone. Results of the survey were examined to determine the impact of individual, environmental, and economic factors on adherence to recommended screening practices for breast cancer. Results indicate a significant proportion of women are not adhering to recommended practices. Preventive health practices were positively related to physician recommendation of a mammogram and how the physician communicated with the patient; patient's income; belief in Powerful Others Locus of Control; and beliefs about the efficacy of early diagnosis and treatment. Fear of breast cancer was negatively related to preventive health practices. Findings highlight the utility of an ecological perspective in the development of secondary prevention strategies for breast cancer. PMID- 7775842 TI - Cancer information service. The National Cancer Institute's link to the community. PMID- 7775844 TI - The Orleans Parish Medical Society's "doctors in the schools" anti-tobacco education program. PMID- 7775843 TI - Historical profiles of toxic chemicals in urban and rural Louisiana lake sediments: epidemiological significance. AB - Sediment cores collected from lakes in rural and urban/industrial areas of Louisiana were dated using 137Cs, sectioned, and analyzed for a wide range of pollutant chemicals deposited during the period 1950 to 1991. Mutagenicity testing also was performed on extracts from the cores. Statistical and other comparisons of chemical data indicated that annual loadings of polycyclic aromatic hydrocarbons (PAHs), chlorinated chemicals, and toxic trace metals were not significantly different in the urban lake versus the rural lake over the historical period compared. Mutagenic activity was detected in both lakes, primarily in sediments deposited between 1955 and 1980, with minimal activity before and after that period. This was a time of widespread industrial and agricultural activity in Louisiana, before restrictions on chemical releases to the environment were instituted and enforced. PMID- 7775845 TI - From product to process in curriculum planning: a view from Britain. AB - I visited California in 1989 in order to meet Mary Poplin at the Claremont Graduate School. I had been deeply impressed by her two articles that had appeared the previous year in the Journal of Learning Disabilities (Poplin, 1988a, 1988b). It is always such a pleasure to meet someone of like mind. (The meeting seemed particularly poignant in light of the fact that at that time, back in Britain, the National Curriculum was rearing its ugly head.) The work of Lous Heshusius (1982, 1989, 1991, 1992) and Richard Iano (1986, 1989, 1990) has also given me much encouragement. All three writers rightly reject "reductionism" in special education and support an alternative world view: holism. I am very concerned about the way that Individualized Education Programs (IEPs) dominate special education in both North America and Britain. The purposes of this article are to sketch an account of the rise of IEPs in Britain, to expose some problems presented by the behavioral objectives model and its associated IEPs, to introduce an alternative model--the process model--and to show the shift from a product to a process approach in curriculum planning. PMID- 7775846 TI - Responsible inclusion for students with learning disabilities. AB - The purpose of this article is to contrast responsible with irresponsible inclusion practices for students with learning disabilities. Guidelines for responsible inclusion are that the student and family are considered first, teachers choose to participate in inclusion classrooms, adequate resources are provided for inclusion classrooms, models are developed and implemented at the school-based level, a continuum of services is maintained, the service delivery model is evaluated continuously, and ongoing professional development is provided. PMID- 7775848 TI - Homework practices of students with and without learning disabilities: a comparison. AB - This article describes a study examining the homework practices of 48 students with learning disabilities and a matched sample of 48 nondisabled students. Students ranged in age from 11 to 15 years and attended Grades 6 through 8. Students in both groups completed the Student Survey of Homework Practices, a 27 item, Likert-type questionnaire examining students' homework practices and attitudes toward homework. Results indicated that although there were some similarities in the homework practices of both groups, the students with learning disabilities engaged to a significantly greater extent in practices that interfered with homework completion. Suggestions for increasing the homework completion rates of students with learning disabilities are provided. PMID- 7775847 TI - Verbal and visual problems in reading disability. AB - Most individuals interested in reading disability favor the view that disordered language processing is the main cause of children's reading problems and that visual problems are seldom, if ever, responsible. Nevertheless, in a preliminary study (Eden, Stein, & Wood, 1993) we showed that visuospatial and oculomotor tests can be used to differentiate children with reading disabilities from nondisabled children. In the present study we investigated a larger sample of children to see if these findings held true. Using 93 children from the Bowman Gray Learning Disability Project (mean age = 11.3 years; 54 boys, 39 girls), we compared the phonological and visuospatial abilities of nondisabled children (children whose reading at fifth grade rated a Woodcock-Johnson reading standardized score between 85 and 115), and children with reading disability (whose reading standardized score was below 85 on the Woodcock-Johnson). In addition to performing poorly on verbal tests, the children with reading disability were significantly worse than nondisabled children at many visual and eye-movement tasks. A high proportion of the variance (68%) in reading ability of both the nondisabled children and those with reading disability could be predicted by combining visual and phonological scores in a multiple regression. These results provide further support for the hypothesis that reading disability may, to some extent, result from dysfunction of the visual and oculomotor systems. PMID- 7775849 TI - Impaired recognition of traffic signs in adults with dyslexia. AB - Ten adults with dyslexia (4 women and 6 men, mean age: 26.8 years, range: 19-43 years) and 11 controls (5 women and 6 men, mean age: 20.5 years, range: 18-29 years) were tested on their ability to differentiate between real and false traffic signs. The stimuli, computer-presented color pictures, were chosen to minimize the applicability of verbal or written linguistic skills to the task. The adults with dyslexia recognized the traffic signs significantly less well than did the controls. Furthermore, whereas for the controls there was a significant correlation between traffic sign recognition and driving experience, no such correlation was found for the adults with dyslexia. The results are interpreted in terms of a deficit in implicit learning. PMID- 7775851 TI - Subtle symptoms associated with self-reported mild head injury. AB - We conducted a survey on the relationship between mild head injury incidence and a variety of psychological and educational symptoms in a sample of 1,345 high school and 2,321 university students. Once figures were adjusted to represent a 50:50 gender ratio, 30% to 37% of subjects reported having experienced a head injury incident, with 12% to 15% of the total group of subjects reporting such an incident with loss of consciousness. We found significant relationships between the incidence of such mild head injury and gender, sleep difficulties, social difficulties, handedness pattern, and diagnoses of attention deficit, depression, and speech, language, and reading disorders. PMID- 7775850 TI - Fable comprehension by children with learning disabilities. AB - Seven fables were read to 14 average learners and 14 children with learning disabilities, all of whom ranged in age from 10 to 13 years. They were presented with four possible moral choices: one correct, one related, and two incorrect. They were instructed to select the correct moral choice and were asked to explain their choice. The average learners' ability to select the correct moral was significantly better than that of the children with learning disabilities. In addition, even when they chose correct morals, the children with learning disabilities were less capable of explaining their choice. PMID- 7775853 TI - Polarized secretion of apoA-I and apoA-II by transfected MDCK cells. AB - Apolipoproteins (apo) are secreted preferentially from the basolateral surface of hepatocytes and enterocytes. The polarized secretion of proteins is either mediated by a protein-dependent sorting signal or by a cell-dependent default pathway. In order to determine the mechanism for the polarized secretion of apolipoproteins, we examined the secretion of apoA-I and apoA-II in transfected Madin-Darby canine kidney (MDCK) cells. Transfected MDCK cells and Caco-2 cells were grown as a polarized monolayer on tissue culture inserts, which separate an upper apical compartment from the lower basolateral compartment, and the secretion of apoA-I and apoA-II into the apical and basolateral compartments was quantitated by immunoprecipitation. Caco-2 cells almost exclusively secreted apoA I and apoA-II basolaterally, with an apical to basolateral ratio of 18:82 for apoA-I, and 11:89 for apoA-II. In contrast, transfected MDCK cells secreted significant amounts of apoA-I and apoA-II into both compartments, but with a bias toward apical secretion and an apical to basolateral ratio of 66:34 and 68:32, respectively. The polarized secretion of MDCK cells was not due to transcytosis, diffusion, or differential recovery. As assessed by density gradient ultracentrifugation, apoA-I and apoA-II secreted from either the apical or basolateral surface were relatively lipid-poor. Overall, these results suggest that the polarized secretion of apoA-I and apoA-II does not occur by a protein dependent sorting signal, but by a cell-dependent default pathway that leads to preferential basolateral secretion by Caco-2 cells and both apical and basolateral secretion in MDCK cells, but with a bias toward apical secretion. PMID- 7775852 TI - Assembly of very low density lipoproteins in rat liver: a study of nascent particles recovered from the rough endoplasmic reticulum. AB - To investigate the assembly pathway for hepatic very low density lipoproteins (VLDL), nascent lipoproteins were recovered from a purified, intact rough endoplasmic reticulum (ER) fraction isolated from rat liver. Two fractions were recovered by ultracentrifugation. Particles isolated at d 1.006 g/ml were triglyceride-rich particles containing apolipoprotein (apo)B-100 or apoB-48, and apoE with very small amounts of apoA-I. Compared with VLDL recovered from the Golgi apparatus, the particles from the rough ER had less triglyceride, but more cholesteryl ester and phospholipid. The second class of particles isolated between d 1.006 and 1.210 g/ml were phospholipid-rich and contained apoB-48, apoE, and apoA-I. ApoB-100 was a minor component. Radioisotope incorporation studies utilizing [3H]leucine revealed differential rates of labeling of the apoproteins in these two lipoprotein fractions. ApoB-100 and apoE followed similar patterns in both fractions with peak incorporation occurring within 15 min of isotope injection. Incorporation of [3H]leucine into apoB-48 in the dense fraction peaked within 15 min of isotope administration, but peak incorporation in the d 1.006 g/ml fraction did not occur until approximately 30 min after injection. We propose that the two lipoprotein fractions recovered from the rough ER are intermediates in the assembly of VLDL by the liver. Comparison of the composition of these two particles with that of Golgi VLDL supports the sequential assembly of VLDL by the liver. Furthermore, we propose that the initial steps in the assembly of apoB-100- and apoB-48-containing lipoproteins are different with nascent apoB-100-containing particles being formed through the cotranslational association of this apoprotein with lipid while nascent apoB-48 containing VLDL are formed in the rough ER through a two-step process. PMID- 7775854 TI - Tissue-specific, developmental and nutritional regulation of the gene encoding the catalytic subunit of the rat apolipoprotein B mRNA editing enzyme: functional role in the modulation of apoB mRNA editing. AB - Apolipoprotein B (apoB) mRNA editing, a posttranscriptional site-specific cytidine deamination reaction, is mediated by a protein complex of which the catalytic component (REPR) has recently been cloned. REPR mRNA was demonstrated by RNase protection at highest abundance in small intestine and colon but the transcript was detectable in all tissues examined including kidney, spleen, lung, liver, and ovary. ApoB mRNA was found predominantly in the liver and small intestine but low levels were detected in all adult tissues examined and found to be variably (29-86% TAA) edited. In addition, S100 extracts prepared from spleen and kidney were competent to edit an apoB RNA template in vitro, suggesting that the entire apoB mRNA editing complex is present and functionally active in these tissues. In situ hybridization demonstrated REPR mRNA to be distributed along the entire villus-crypt axis, while apoB mRNA distribution did not extend into the crypts. In the liver, both apoB and REPR mRNA were detected in all cells of the hepatic lobule without an apparent gradient of expression. REPR mRNA was found in the red pulp of the spleen and in the superficial crypt cells of the colon. This distribution of REPR mRNA was recapitulated by immunocytochemical localization of the protein within these tissues. Finally, the developmental and nutritional modulation of REPR was examined in relation to endogenous apoB mRNA editing. Small intestinal apoB mRNA editing was found to undergo a developmentally regulated increase beginning at gestational day 20, preceding a developmental increase in REPR mRNA abundance. Additionally, hepatic and kidney apoB mRNA editing both revealed a temporal dissociation from alterations in REPR mRNA abundance. By contrast, adult rats subjected to fasting and refeeding a high carbohydrate diet, demonstrated concordant modulation of endogenous apoB mRNA editing and REPR mRNA abundance (r = 0.92, P < 0.001). Taken together, the data demonstrate that REPR and other components of the rat apoB mRNA editing complex are widely distributed and undergo distinct developmental and metabolic regulation that interact to regulate apoB mRNA editing in a tissue-specific manner. PMID- 7775855 TI - Structural basis of the phospholipid acyltransferase enzyme substrate specificity: a computer modeling study of the phospholipid acceptor molecule. AB - The activity of the 1-acyl-sn-glycero-3-phosphocholine acyltransferase enzyme (E.C. 2.3.1.??) was measured with three radically different acceptor substrates: 1-palmitoyl-sn-glycero-3-phosphocholine (P-sn-G3PC), 1-palmitoyl-sn-glycero-2 phosphocholine (P-sn-G2PC), and 1-hexadecyl-sn-glycero-3-phosphocholine (He-sn G3PC). It was found that the enzyme had similar activity with P-sn-G3PC, the natural acceptor substrate, and with P-sn-G2PC. The enzyme showed no detectable activity toward He-sn-G3PC. These results are much different than would be expected from simple examination of the structures. Computer-assisted molecular modeling was done to study the geometrical configurations and to focus upon the similarities and differences of the three substrate acceptor molecules. Three bond distances were selected as important for enzyme recognition: the distance between the oxygen of the acceptor hydroxyl group and 1) the phosphorus; 2) the nitrogen; and 3) the oxygen bridge to the hydrocarbon chain. There were striking similarities for the bond distances of two of the three acceptor substrates, P-sn G3PC and P-sn-G2PC. These were the two molecules that were shown to have activity with the enzyme. The bond distances found for the enzymically inactive acceptor substrate, He-sn-G3PC, differed significantly from P-sn-G3PC and P-sn-G2PC. Therefore, this latter molecule probably does not fit into the active site of the enzyme. The modeling data are also consistent with the experimental observation that He-sn-G3PC is not an inhibitor. PMID- 7775856 TI - Coenzyme A-dependent modification of fatty acyl chains of rat liver membrane phospholipids: possible involvement of ATP-independent acyl-CoA synthesis. AB - Certain species of fatty acyl chains of microsomal lipids from rat hepatocytes underwent desaturation when the microsomal fraction was incubated with CoA and NADH. For instance, 18:0, 18:2(n-6), and 20:3(n-6) incorporated into membrane lipids were gradually converted to 18:1(n-9), 18:3(n-6), and 20:4(n-6), respectively. Further, 20:5(n-3) and 18:3(n-6) were metabolized to 22:5(n-3) and 20:4(n-6) respectively, through chain elongation or chain elongation plus subsequent desaturation when malonyl-CoA was present. In contrast to esterified fatty acids, negligible change was observed for fre fatty acids under the same experimental conditions. It is apparent that ATP-independent acyl-CoA synthesis is implicated in such enzymatic modification of fatty acyl chains. The presence of either gel-filtered cytosol or bovine serum albumin markedly potentiated the reaction. However, the addition of ATP and Mg2+ did not accelerate the overall reaction induced in the presence of CoA alone. These results suggest that the pathway of CoA-dependent/ATP-independent modification of fatty acyl chains is sufficiently active to account for the desaturation and chain elongation of fatty acids esterified in membrane lipids, especially phospholipids, of living cells. PMID- 7775857 TI - Control of lipolysis in intra-abdominal fat cells of nonhuman primates: comparison with humans. AB - The mechanisms that control lipolysis in intra-abdominal fat cells from various primate species, the marmoset (Callithrix jacchus), the baboon (Papio papio), and the macaque (Macaca fascicularis), were compared to those of human intraabdominal fat cells. Selective beta 1- or beta 2-adrenoceptor agonists induced lipolysis in all species. Selective beta 3-agonists (BRL 37344, CL 316243, and SR 58611) acted as partial agonists in marmoset but were inefficient in other primates, including humans. alpha 2-Adrenoceptor number ([3H]RX 8210002 binding) equalized (baboon) or exceeded (other primates) beta 1/beta 2-adrenoceptors ([3H]CGP 12177 binding). Baboon fat cell membranes expressed similar amounts of coupled beta- and alpha 2 adrenoceptors. In all species, norepinephrine- or epinephrine-induced lipolysis did not reach the lipolytic effect of isoproterenol but their effects were enhanced after alpha 2-adrenoceptor blockade. N6-phenylisopropyladenosine (PIA) induced a full antilipolytic effect in baboon, macaque, and human adipocytes through adenosine receptors ([3H]DPCPX binding). Peptide YY (PYY) weakly inhibited lipolysis in baboon. Adrenocorticotropic hormone (ACTH) was inactive whereas parathyroid hormone (PTH) partially stimulated lipolysis in primates. Histamine was partially lipolytic in marmoset only. This study emphasizes the similarities of the mechanisms controlling the lipolysis in nonhuman primate and in human adipocytes and suggests that the baboon and the macaque should provide unique models for the study of the regulation of lipolysis. PMID- 7775858 TI - Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipoprotein subclasses. AB - To test whether lipoprotein lipase or hepatic lipase activities are associated with lipoprotein subclasses, and to assess the effects of dietary manipulations on these associations, enzyme activities were measured in postheparin plasma (75 U heparin/kg) from 43 healthy men who were randomly allocated to a low-fat (24% fat, 60% carbohydrate) and a high-fat (46% fat, 38% carbohydrate) diet for 6 weeks each in a cross-over design. The high-fat diet significantly increased both lipoprotein lipase (+20%, P = 0.02) and hepatic lipase (+8%, P = 0.007) activities. On both diets, hepatic lipase activity was significantly positively correlated (P < 0.01) with plasma apolipoprotein (apo)B concentrations, and with levels of small dense low density lipoprotein (LDL) III, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Sof) 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL III (P < 0.05). Despite the cross-sectional correlations, increased hepatic lipase activity was not significantly correlated with the reduction in LDL III mass observed on the high-fat diet. Rather, changes in hepatic lipase were correlated inversely with changes in small very low density lipoproteins (VLDL) of Sof 20 40, and small intermediate density lipoproteins (VLDL) of Sof 10-16. Moreover, changes in lipoprotein lipase activity were not significantly correlated with changes in small LDL, but were positively associated with changes in small IDL of Sof 10-14, and large LDL I of Sof 7-10. Thus, while increased levels of small dense LDL are associated with a metabolic state characterized by relatively increased hepatic lipase and decreased lipoprotein lipase activity, changes in these enzymes do not appear to be primary determinants of diet-induced changes in levels of this LDL subfraction. On the other hand, increased lipoprotein lipase activity induced by high-fat feeding may contribute to the accumulation in plasma of both large LDL I and small IDL, whereas increased hepatic lipase may promote catabolism or clearance of triglyceride-rich lipoprotein remnants. PMID- 7775859 TI - Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages. AB - The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive subjects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil. Fish oil significantly (-24%, P < 0.01) reduced plasma triglyceride, and increased LDL-cholesterol (+6%, P < 0.01 compared to corn oil). LDL particles were larger (P < 0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P < 0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P < 0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P < 0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P < 0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable. PMID- 7775861 TI - Characterization of stratum corneum structure in reconstructed epidermis by X-ray diffraction. AB - The intercellular lipid regions in the stratum corneum (SC), the outermost layer of the skin, form the major barrier for diffusion of substances through the skin. The barrier function of in vitro reconstructed epidermis is still impaired. With respect to further optimization of the model, it is necessary to characterize its stratum corneum lipid structure. In this study, small and wide angle X-ray diffraction were used to characterize the lipid organization in stratum corneum isolated from 14-day-old reconstructed epidermis. The measurements were carried out at room temperature, and subsequently as a function of temperature between 25 degrees C and 109 degrees C, followed by measurements after cooling to room temperature. The results of the X-ray diffraction measurements revealed the following in reconstructed epidermis. 1) The lamellar ordering of stratum corneum lipids was much lower than that observed in native stratum corneum. 2) Crystalline anhydrous cholesterol was present. 3) Orthorhombic packing was present, but the corresponding reflections were very weak. The orthorhombic packing disappeared between 30 degrees C and 45 degrees C. 4) A hexagonal packing was present and disappeared between 60 degrees C and 75 degrees C. 5) Soft keratin is present. 6) A higher extent of lamellar ordering could be achieved by heating to 109 degrees C and cooling down to room temperature. Analysis of SC lipids revealed the presence of high amounts of triglycerides, the level of which could be decreased by lowering the glucose content. However, modulation of culture medium composition did not significantly affect lipid lamellae structures or hydrocarbon chain packing. PMID- 7775860 TI - Plasma lipid transport in the hedgehog: partial characterization of structure and function of apolipoprotein A-I. AB - Apart from exhibiting the presence of lipoprotein [a] in its plasma, another interest of the European hedgehog in lipoprotein research lies in the quantitative prominence of a complex spectrum of high density lipoproteins (HDL) and very high density lipoproteins (VHDL) as cholesterol transporters in plasma (Laplaud, P. M. et al. 1989. Biochim. Biophys. Acta. 1005: 143-156). We, therefore, initiated studies in the field of reverse cholesterol transport in the hedgehog. As a first step, we characterized apolipoprotein A-I (apoA-I), the main protein component of hedgehog HDL and VHDL. Proteolytic cleavage of apoA-I (M(r) approx. 27 kDa) using two different enzymes resulted in two sets of peptides that were subsequently purified by high performance liquid chromatography, and that allowed us determination of the complete protein sequence. Hedgehog apoA-I thus consists of 241 amino acid residues and exhibits an overall 58% homology to its human counterpart, i.e., the lowest value observed to date among mammalian species. However, it retained the general organization common to all known apoA Is, i.e., a series of amphipathic helical segments punctuated by proline residues. Circular dichroism experiments indicated a helical content of approx. 45%, increasing to approx. 58% in the presence of lecithin unilamellar liposomes. Apart from other differences, amino acid composition analysis shows that hedgehog apoA-I contains four isoleucine residues, while this amino acid is totally absent from the corresponding protein in higher mammals. Polyclonal antibodies raised against hedgehog apoA-I failed to detect any cross-reactivity between the animal and human proteins, although comparative prediction of the respective antigenic structures using the Hopp-Woods algorithm indicated that several potentially antigenic sites may occur in similar regions of the protein. Finally, hedgehog apoA-I was shown to be able to activate lecithin:cholesterol acyl transferase, although it was 4 to 5 times less efficient in this respect than the human protein. PMID- 7775862 TI - Inhibition of cellular cholesterol efflux by 25-hydroxycholesterol. AB - The effect of oxysterols on efflux of cholesterol from mouse L-cell fibroblasts, rat Fu5AH hepatoma cells, J774 macrophages, and human EA.hy 926 endothelial cells was studied. Cells were preincubated with 25-hydroxycholesterol (25-OHC) either during labeling of the cells with [3H]cholesterol or during equilibration after labeling. Subsequently, the release of [3H]cholesterol into medium containing 0.2 mg HDL3/ml was measured and the fractional release of cellular [3H]cholesterol was calculated. Pretreatment with 25-OHC (1 microgram/ml) caused a 30% reduction in [3H]cholesterol efflux from L-cells during 8 h of incubation with HDL3. 25-OHC also inhibited cholesterol efflux from Fu5AH and J774 cells, but the effect was less marked. There was only a small, nonsignificant reduction of efflux from EA.hy 926 cells. The mechanisms of 25-OHC-induced inhibition of cellular cholesterol efflux was further studied in L-cells, because of their sensitivity to 25-OHC treatment. The effect of 25-OHC on cholesterol efflux was dose dependent, with significant effects seen at 25-OHC concentrations as low as 50 ng/ml. The half-time for cholesterol efflux from 25-OHC-treated cells (5 micrograms/ml) was 13.0 +/- 3.3 h compared to 5.7 +/- 1.0 in control cells, corresponding to a 55% reduction in the rate of cholesterol release. Other oxysterols, including 7-ketocholesterol, 7 alpha- and 7 beta-hydroxycholesterol, and 22(S)-hydroxycholesterol also inhibited [3H]cholesterol efflux from L-cells significantly, but to a lesser degree. 25-Hydroxycholesterol (5 micrograms/ml) reduced efflux from both normal and cholesterol-enriched cells by 31 and 14%, respectively. Inhibition of efflux was similar when reconstituted HDL3 apolipoprotein/phosphatidylcholine particles or small unilamellar phosphatidylcholine vesicles were used as cholesterol acceptors instead of HDL3. The content of phospholipids, cholesterol and the FC/PL ratio of intact cells and from isolated plasma membrane vesicles were the same for control and 25-OHC treated cells. Efflux of [3H]cholesterol from plasma membranes isolated from 25 OHC-treated cells was 20% less than efflux from membranes from control cells. The difference in efflux observed in intact cells is partially explained by the reduction in efflux from the plasma membrane. In conclusion, our studies suggest that oxysterols, especially 25-hydroxycholesterol, can reduce cellular cholesterol efflux in vitro. Therefore oxysterols, either endogenous or derived from the diet, may influence cellular cholesterol efflux in vivo, the first step in reverse cholesterol transport. PMID- 7775863 TI - Apolipoprotein E isoforms and rare mutations: parallel reduction in binding to cells and to heparin reflects severity of associated type III hyperlipoproteinemia. AB - The LDL receptor-independent binding of human apolipoprotein E isoforms and rare apoE mutations were studied on LDL receptor-deficient human fibroblasts using chemical cross-linking and cell binding studies. The cross-linking experiments demonstrated that all apoE variants bind to the low density lipoprotein receptor related protein, a potential receptor for remnant lipoproteins. In cell binding studies, the effect of the apoE variants on binding of beta-VLDL was investigated. Addition of normal apoE-3 to the binding assay resulted in a 12 fold increase of beta-VLDL particle binding, whereas this effect was reduced in the clinically defective variants: apoE-2, (Arg158-->Cys), 24.4% of apoE-3; apoE 1, (Gly127-->Asp, Arg158-->Cys), 49.2% of apoE-3; apoE-1(Lys146-->Glu), 18.2% of apoE-3. Heparin binding studies with the same variants showed a parallel reduction in proteoglycan binding (apoE-2(158), 58.2% of apoE-3; apoE-1(127,158), 37.9%; apoE-1(146), 20.6%). We conclude that LDL receptor-independent mechanisms contribute to remnant clearance. The functionally dominant mutation apoE-1(146) was most defective in heparin binding studies in vitro. In cell binding studies, apoE-1(146) did mediate lipoprotein binding only 18% compared to apoE-3. This indicates the important role of the apoE interaction with proteoglycans in vivo and could explain the development of type III hyperlipoproteinemia in patients with such apoE variants. PMID- 7775864 TI - Characterization of constitutive human serum amyloid A protein (SAA4) as an apolipoprotein. AB - Serum amyloid A proteins (SAAs), a family of homologous molecules, are apolipoproteins of high density lipoprotein (HDL). They can be divided into two groups. The first group comprises the well-characterized acute phase SAAs that associate with HDL during inflammation, thereby remodeling the HDL particle by displacing apolipoprotein (apo)A-I. The second group consists of the recently discovered constitutive SAAs, mouse SAA5 and human SAA4. They exist as minor apolipoproteins on HDL but constitute more than 90% of the total SAA during homeostasis. We have characterized human SAA4 as an apolipoprotein. During homeostasis, SAA4 is synthesized only in the liver. Purification of SAA4 has been described and its plasma concentration has been established at 55 +/- 13 micrograms/ml in 26 healthy individuals. It was present on all HDL density classes and very low density lipoprotein (VLDL) but was absent from low density lipoprotein (LDL). Using two-dimensional electrophoresis and phosphorimaging, SAA4 was found to be associated with a specific subpopulation of only three HDL particles, not involved in the initial cholesterol transfer from cells. PMID- 7775865 TI - Tetradecylthioacetic acid (a 3-thia fatty acid) decreases triacylglycerol secretion in CaCo-2 cells. AB - The effects of the hypolipidemic fatty acid analogue tetradecylthioacetic acid (TTA) on synthesis and secretion of lipoproteins in CaCo-2 cells were studied. Radiolabeled tetradecylthioacetic acid was absorbed and metabolized as efficiently as oleic acid, although a discrepancy in the metabolic fate was evident. Whereas tetradecylthioacetic acid was incorporated into cell-associated triacylglycerol to the same extent as normal fatty acids (e.g., oleic acid and palmitic acid), the amount of triacylglycerol secreted from cells incubated with tetradecylthioacetic acid was 8 to 10 times lower than the amount secreted from cells incubated with palmitic acid and oleic acid, respectively. On the other hand, there was an enhanced incorporation of tetradecylthioacetic acid into cell associated and secreted phospholipids. Despite incorporation of tetradecylthioacetic acid into cellular triacylglycerol, unlike oleic acid, tetradecylthioacetic acid did not stimulate production of triacylglycerol-rich particles. Ultracentrifugation of basolateral media from cells incubated with tetradecylthioacetic acid revealed low amounts of triacylglycerol in the triacylglycerol-rich fraction (p < 1.006 g/ml), suggesting secretion of lipoproteins with a higher density than chylomicrons. However, the present study shows that the stimulated triacylglycerol secretion caused by oleic acid was inhibited in the presence of TTA. The decreased rate of triacylglycerol secretion from these cells was not accompanied by a stimulation of fatty acid oxidation. Based on these findings, we therefore suggest that tetradecylthioacetic acid mainly affects secretion of lipoproteins in CaCo-2 cells. PMID- 7775866 TI - Progesterone blocks intracellular translocation of free cholesterol derived from cholesteryl ester in macrophages. AB - Macrophage foam cells must accommodate continuing fluxes of free cholesterol in spite of a greatly expanded store of cholesteryl ester. Though endogenous free cholesterol synthesis is suppressed, free cholesterol continues to enter the cell via endocytosis of oxidized/modified lipoproteins. It has been shown previously that this free cholesterol is released into the lysosomal compartment and rapidly transported to the plasma membrane prior to its esterification. A substantial amount of free cholesterol is also presented via the continuous hydrolysis of cholesteryl ester during the cholesteryl ester cycle. We addressed the question of whether the intracellular free cholesterol derived from the hydrolysis of cholesteryl ester formed a protected pool for rapid re-esterification. Incubation of macrophage foam cells with cyclic AMP to enhance cholesteryl ester hydrolysis, and with S58035 to inhibit acyl-CoA:cholesterol acyltransferase (ACAT) activity, led to conversion of cellular cholesteryl ester to free cholesterol and transport of this free cholesterol to the plasma membrane. Addition of progesterone, previously demonstrated to be an inhibitor of free cholesterol transport in other cell types, also led to conversion of cholesteryl ester to free cholesterol even though progesterone was only a weak inhibitor of ACAT activity. Free cholesterol in the plasma membrane was an important source of ACAT substrate to balance the constitutive hydrolysis of cholesteryl ester in cholesterol-loaded macrophages. Treatment of cells with progesterone, however, prevented free cholesterol derived from cholesteryl ester hydrolysis from moving to the plasma membrane. The sequestration of free cholesterol by progesterone could be reversed by incubation with human HDL3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775867 TI - Modulation in delta 9, delta 6, and delta 5 fatty acid desaturase activity in the human intestinal CaCo-2 cell line. AB - We report the influence of media lipids, growth in lipid-poor medium, and cell differentiation on delta 9, delta 6, and delta 5 desaturase activity in the human CaCo-2 enterocyte cell line. We also describe the level of incorporation of palmitic (16:0), linoleic (18:2n-6), and eicosapentaenoic (EPA) acids (20:5n-3) and their higher homologues into cytosolic and membrane lipids during long-term (10 days) medium supplementation in fully differentiated 16- to 18-day-old cultures. CaCo-2 monolayers reached confluency by day 6 with subsequent development of microvilli and maximal expression of microvillus membrane sucrose, alkaline phosphatase, and gamma-glutamyltransaminase occurring between days 16 and 23 after plating. There was evidence of the presence and modulation of delta 9, delta 6, and delta 5 desaturase activity (delta 9 > delta 6 > delta 5). delta 6 Desaturase activity decreased approximately 2-fold between days 6 and 24 of culture and when the fetal bovine serum concentration was increased from 0.5% to 25%; in contrast, when cells were starved for 72 h, activity increased 5.4-fold. When the media was supplemented with either linoleic acid and/or EPA, both delta 6 and delta 5 desaturase activities were inhibited, the greatest reduction of delta 5 desaturase activity occurring with EPA. Incorporation of media fatty acids plus their desaturase and elongase products was highly dependent on medium composition with the homologues of delta 9 > delta 6 > delta 5. Supplementation of cellular media with 100 microM EPA for 10 days decreased membrane phosphatidylethanolamine arachidonic acid level from 13.2 to 8.9%. From these results we conclude that enterocyte membrane fatty acid composition and desaturase enzyme activity are regulated by both dietary fat intake and cell maturation. The clinical relevance of these observations on lipid dietary modification for the management of chronic inflammatory bowel disease is still uncertain but these observations suggest that the beneficial effects of EPA supplements on human ulcerative colitis may be due to a reduction in enterocyte arachidonic acid content by down-regulation of delta 6 and delta 5 desaturase activity. PMID- 7775868 TI - Distribution of exogenously added gangliosides in serum proteins depends on the relative affinity of albumin and lipoproteins. AB - Gangliosides in normal serum are found only in lipoproteins and the relative content of the three major lipoprotein fractions is low density lipoprotein > high density lipoprotein > very low density lipoprotein (LDL > HDL > VLDL). Upon in vitro incubation of labeled gangliosides with human serum, about 15% of the exogenous gangliosides became associated with the albumin fraction and 85% were distributed on the lipoproteins in the order HDL > LDL > VLDL. To compare the relative affinities of serum proteins for gangliosides, the levels of exchange of exogenous gangliosides between preloaded serum proteins were determined. Although albumin had the highest binding capacity for gangliosides, 85% of the albumin loaded gangliosides were transferred to the total lipoprotein fraction and this exchange was reversible. The transfer rate from albumin to isolated lipoproteins was higher to LDL (90%) and HDL (85%) whereas only 55% of albumin-loaded gangliosides were transferred to VLDL. The study of exchanges of preloaded gangliosides between isolated lipoproteins showed that the extent of transfer of gangliosides from a given lipoprotein fraction onto other lipoproteins was inversely correlated with its endogenous ganglioside content. Moreover, in the absence of albumin from the incubation medium, the final lipoprotein distribution of remaining exogenous gangliosides was similar to the normal distribution of endogenous gangliosides in serum lipoproteins. The formation of unexchangeable complexes between albumin and micellar exogenous gangliosides could be a possible explanation for the observed differences in the distribution of exogenous and endogenous gangliosides in serum proteins. PMID- 7775869 TI - High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease. AB - High density lipoprotein (HDL) subfractions (2b, 2a, 3a, 3b, and 3c) separated by gradient gel electrophoresis (GGE) and defined by Gaussian summation analysis, and the compositions of HDL2 and HDL3, separated by preparative ultracentrifugation, were studied in four groups of men with or without non insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD): group 1 (DM+CAD+, n = 50); group 2 (DM-CAD+, n = 50); group 3 (DM+CAD-, n = 50); and group 4 (DM-CAD-, n = 31). HDL GGE subfraction distributions, available in 125 subjects, were not significantly different among the groups. In contrast, dividing the whole study population into quartiles of serum triglyceride (TG) concentration showed that high TG levels were significantly associated with low HDL2b and high HDL3b concentrations. In a multivariate linear regression model, postheparin plasma hepatic lipase (HL) activity, and fasting serum insulin and TG concentrations were all associated independently and inversely with low HDL2b, but lipoprotein lipase or cholesteryl ester transfer protein activities were not correlated with HDL2b concentrations. Group 1 tended to have the smallest mean particle sizes in the HDL subfractions, significantly (P < 0.03, CAD vs. non-CAD) for HDL2b and for HDL2a. These differences were independent of TG, insulin and HL, but lost their significance when adjusted for beta-blocker therapy. Both HDL2 and HDL3 particles in group 1 were significantly depleted of unesterified cholesterol, and their HDL2 was TG-enriched (P = 0.053). A high HL activity, hyperinsulinemia and hypertriglyceridemia are independently associated with low levels of HDL2b and generally small HDL particle size. HDL particles in subjects with NIDDM and CAD are small-sized and have a low free cholesterol content. Both these characteristics may be markers of impaired reverse cholesterol transport. PMID- 7775870 TI - Selective uptake of HDL cholesteryl esters is active in transgenic mice expressing human apolipoprotein A-I. AB - The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while selective uptake played a role in normal animals, it did not in transgenic mice which express predominantly human apoA-I (Chajek-Shaul et al., 1991. Proc. Natl. Acad. Sci. USA. 88: 6731-6735);thus human apoA-I was apparently unable to support selective uptake. These conclusions rested on plasma decay data that represent a composite of all tissue and which may obscure tissue-specific factors. Thus we reexamined the matter by measuring the rates of uptake of HDL components by individual tissues using intracellularly trapped tracers. Plasma decay data were much as reported in the referenced study. Nonetheless the fractional rate of uptake of HDL CE was greater than that of apoA-I in adrenal gland and liver, indicating selective uptake. Kidney took up apoA-I tracer at a greater fractional rate than CE tracer, apparently by filtration and reabsorption of free apoA-I, and this uptake was at a greater fractional rate in the transgenic mice than in normal mice. Thus, the lack of evidence for selective uptake in the plasma decay data of the transgenic mice was explained by a higher rate of renal uptake of apoA-I and not by a diminished rate of selective uptake in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775871 TI - Chicken yolk contains bona fide high density lipoprotein particles. AB - Lipoproteins, the major nutrient source for developing embryos in egg-laying species, are thought to be transported from the circulation of the hen to the yolk of growing oocytes. In order to fully understand the contribution of the different lipoprotein species to oocyte growth, yolk formation, and embryo development, we have started to elucidate the relationships between the high density lipoproteins (HDL) in serum with the hitherto uncharacterized yolk HDL fraction. Immunoblotting with antibodies against apolipoprotein (apo) A-I, the major protein moiety of circulating HDL, revealed, for the first time, significant amounts of this protein in yolk. Importantly, yolk apoA-I was an integral component of bona fide lipoprotein particles: i) the apoA-I-containing particles could be purified by ultracentrifugal flotation and immunoaffinity chromatography on immobilized anti-apoA-I IgG; ii) the particles resembled serum HDL in ultrastructural, chemical, and biochemical aspects; and iii) in particular, these particles contained another major apolipoprotein, apo II. To date, apo II has been assumed to be unique to the very low density lipoprotein (VLDL) and HDL fractions of laying hen serum. Its residence on yolk HDL particles, together with the other results, strongly implies that yolk HDL, at least to a large part, is derived from serum. This implication is supported by the presence of apoA-I in oocytic coated vesicles. However, an oocyte plasma membrane receptor for the transport of HDL could not be identified; furthermore, immunoelectron microscopy demonstrated that yolk HDL particles do not colocalize with VLDL, known to be endocytosed via a specific receptor. Thus, these studies have revealed that HDL particles are taken up into the oocyte from the serum of the laying hen, and are deposited into the yolk by a mechanism distinct from that involved in the uptake of other yolk lipoproteins. PMID- 7775872 TI - Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. AB - Analogs and homologs of PDMP were synthesized, based on its structure (D-threo-1 phenyl-2-decanoylamino-3-morpholino-1-propanol). This compound had previously been found to block the synthesis of GlcCer (glucosylceramide). Increasing the acyl chain length from 10 to 16 carbon atoms greatly enhanced the efficacy of the enzyme inhibitor, as did the use of a less polar cyclic amine, especially a pyrrolidine instead of a morpholine ring. Replacement of the phenyl ring by a chain corresponding to sphingosine also yielded a strongly inhibitory material. By using a chiral synthetic route, we showed that the isomers active against GlcCer synthase had the R,R-(D-threo)-configuration. However, strong inhibition of the growth of human cancer cells in plastico was produced by both the threo and erythro racemic compounds, showing involvement of an additional factor (beyond simple depletion of cell glycosphingolipids by blockage of GlcCer synthesis). The growth arresting effects could be correlated with increases in cellular ceramide and diglyceride levels. The aliphatic pyrrolidino compound was strongly inhibitory toward the glucosyltransferase and produced almost complete depletion of glycolipids, but did not inhibit growth or cause an accumulation of ceramide. Attempts were made to see whether the differences in growth effects could be attributed to the influence of the inhibitors on related enzymes (ceramide and sphingomyelin synthase and ceramidase and sphingomyelinase). While some stimulation of enzyme activity was noted, particularly at high inhibitor concentrations (50 microM), these findings did not explain the differing effects of the different inhibitors. The best inhibitors of GlcCer synthase compared favorably in efficacy with some cancer chemotherapeutic drugs in current use when tested with a battery of human cancer cells. PMID- 7775873 TI - A novel assay for cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase activity using reversed-phase ion-pair chromatography: demonstration that Lifibrol (K12.148) modulates the enzyme activity. AB - Cytosolic HMG-CoA synthase and microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase catalyze two sequential steps in the mevalonate pathway. Both enzymes are negatively regulated by cholesterol. Cytosolic HMG-CoA synthase is responsible for the generation of HMG-CoA from acetyl-CoA and acetoacetyl-CoA). We have developed a new method to determine HMG-CoA synthase activity. In this assay, HMG-CoA is formed from acetoacetyl-CoA and labeled acetyl-CoA. The HMG-CoA product is isolated from the reaction mixture by means of reversed-phase ion-pair chromatography. The recovery of the product was always greater than 90%. The average within-batch coefficient of variation for HMG-CoA synthase activity was 5.1%. Using the new assay, we demonstrate that Lifibrol (K12.148), a new hypolipidemic compound, inhibits HMG-CoA synthase. Because our assay is accurate and precise it may become useful in future studies on the regulation and the pharmacological modulation of cytosolic HMG-CoA synthase. PMID- 7775874 TI - Potential bile acid metabolites. 23. Syntheses of 3-glucosides of nonamidated and glycine- and taurine-amidated bile acids. AB - The 3-glucosides of nonamidated lithocholic, chenodeoxycholic, ursodeoxycholic, deoxycholic, and cholic acids, and their double conjugate forms with glycine and taurine were synthesized. The key reactions used were 1) beta-D- glucosidation at C-3 by the Koenigs-Knorr condensation reaction of 3 alpha-hydroxylated bile acid methyl (or p-nitrophenyl) esters with 1 alpha-bromo-1-deoxy-2, 3, 4, 6-tetra-O acetyl-D-glucopyranose in the presence of cadmium carbonate in refluxing benzene; 2) indirect and direct amidations at C-24 by the activated p-nitrophenyl ester and by the diethylphosphorylcyanide methods, respectively, using glycinate ester and taurine as coupling agents; and 3) simultaneous alkaline hydrolysis of the hydroxyl-protecting and ester groups in both the sugar and aglycone moieties. PMID- 7775875 TI - Evaluation of the efficacy of routine BCG vaccination: a case-control study. AB - A case-control study was conducted in a metropolitan region of Cairo, Egypt to determine the protective efficacy of routine BCG Vaccination of infants against childhood pulmonary tuberculosis. A total of 175 cases of children suffering from pulmonary tuberculosis were obtained over 8 months period from hospitals likely to admit such cases in Cairo. Each case was matched to two controls for the district of residence. Vaccination status of cases and controls was ascertained by asking the mothers and confirmed by examination of the left arm of the study children for the scar of BCG vaccination. The overall crude efficacy of BCG vaccination was found to be 53% (CL: 68%, 31%), dropping to 49% (CL: 57%, 25%) after controlling for the confounding effect of crowding index. Potential biases in the study design and their role in over or underestimation of the vaccine efficacy were discussed. PMID- 7775876 TI - Integration of hepatitis B immunization in the Expanded Program on Immunization of the Child Survival Project. AB - The Expanded Program on Immunization (EPI) is a component of the Child Survival Project (CSP) whose objectives are to reduce the incidence rates of six childhood diseases (Measles, Diphtheria, Pertussis, Tetanus, Tuberculosis, Poliomyelitis) and to reduce the number of infant deaths from those diseases by increasing effective vaccination coverage. In 1991, the CSP/EPI developed a national plan to introduce national immunization of infants against hepatitis B in an attempt to control the magnitude and seriousness of the damage which viral hepatitis causes in terms of morbidity, mortality and serious sequelae as hepatitis B is an endemic disease in Egypt causing an important public health problem which requires urgent control. This presentation will discuss the integrated effort undertaken to plan and implement the program, the different challenges it faces, control studies being performed as well as the proposed objectives of the hepatitis B vaccination program. PMID- 7775877 TI - Bacteriology of chronic secretory otitis media in children. AB - One hundred and four effusions from 66 children with CSOM were cultured for aerobic and anaerobic bacteria. Fifty percent of all effusions yielded bacterial growth and Gram negative organisms constituted 69.2% of those isolates. H. influenza was the most commonly isolated organism (36.5%) followed by B. catarrhalis and Str. pneumoniae. All B. catarrhalis, Staph. aureus and pseudomonas isolates were resistant to ampicillin while cefotaxime was active against all the isolated Gram positive and Gram negative bacteria. Considering B lactamase production, all the isolated Staph. aureus were BLPs while in case of Gram negative bacteria, not all the ampicillin resistant strains were BLPs. PMID- 7775878 TI - Study of workload of general medicine specialists working in the health insurance clinics. AB - This study was conducted at 4 of the H.I.O. polyclinics in Alex. with the objective of examining the change in visit rate per 1000 beneficiaries for general medicine specialty at H.I.O. clinics during a 4-year period (1985-1988) and to detect any trends that may have a bearing on the H.I.O. standards for supply of specialists. Data were collected from H.I.O. statistics department, H.I.O. regulations, and also through researcher's observation and specialists' interview. The collected data was used to describe the workload in terms of annual visit rate, actual number of working hours, the specialists' average production hours per day, the specialists' average idle time per day, the estimated number of required specialist working hours per day, and the specialists' recommended working hours per day. The results revealed a rising trend in the rate of use of general medicine specialist services and a definite shortage of supply of general medicine specialists was found in all clinics compared to H.I.O. standards. On the other hand, recommended supply based on specialist opinion was less than the H.I.O. standards but more than the current supply. Accordingly H.I.O. should re-estimate the specialist population standard and should seek the commitment of specialists to the revised standards. PMID- 7775879 TI - Effect of nickel sulfate alone and with ultraviolet light on micronuclei frequency in cultured human lymphocytes. AB - Comutagenic or cocarcinogenic activities have been reported between nickel compounds and UV light. The presence of micronuclei in a binucleated lymphocyte is regarded as an alternative to classical cytogenic methods for monitoring chromosomal damage. The present study aimed to detect this comutagenicity as regards micronuclei induction. Human peripheral lymphocytes were treated with different concentrations of nickel sulfate and/or with UV light at 200 and 1000 ergs/mm2. Cells have been cultured and 100 binucleated cells were counted and the micronuclei frequency recorded. The observed values for all concentrations of nickel sulfate combined with UV were less than expected for an additive response of two agents computed as the combined increase over the values of the control for the metal and UV alone. Caution is advised when interpreting cytogenic values in multiple exposures. PMID- 7775880 TI - Assessment of knowledge, attitudes and practices of expectant mothers in relation to antenatal care in Assiut governorate. AB - This study aims to assess knowledge, attitudes and practices of expectant mothers in relation to ante-natal care in Assiut and to find out factors affecting their knowledge. Attitudes and practices. The present study was carried out in the ante natal clinic at Assiut General Hospital and three Maternal and Child Health Centers in Assiut. Fifty women were selected from each of the previously mentioned settings. A specially designed interview sheet was used to collect the necessary data. It was consisted of four parts. The first part included questions related to individual features of women, the second part included questions related to their family features, the third part concerned with previous obstetrical history of women and their acceptance of pregnancy and the fourth part included questions related to knowledge, attitudes and practices of expectant mother in relation to ante-natal care. The findings of the present study revealed that one quarter of the study sample (25.5%) lacked basic and essential knowledge about ante-natal care, most of older women (88.2%) were more likely to have poor knowledge in relation to ante-natal care, the higher educated women (66.7%) were more likely to have good knowledge about ante-natal care compared to 33.5% of lower educated women. It was also observed that the majority of working women (90%) were more likely to have good ante-natal care knowledge compared to housewives (10%). Most of the primigravida women (88.2%) were more likely to have poor knowledge in relation to ante-natal care compared to 11.8% of women whose gravidity was less than 5. PMID- 7775881 TI - Knowledge and practices of pregnant women in relation to the intake of drugs during pregnancy. AB - The present study was done to assess Knowledge and practices of expectant women regarding drug intake during pregnancy. To achieve this aim, a simple random sample of 400 pregnant women during their last trimester of pregnancy were selected. A specially designed interview schedule was developed and used to collect the necessary data about the study subjects. The interview schedule consisted of four main parts to cover the following: 1. General characteristics of the sample. 2. Obstetrical characteristics of the sample 3. Knowledge about drug intake during pregnancy. 4. Practices of the study subjects in relation to drug intake during pregnancy. 5. Factors affecting their knowledge regarding drug intake during pregnancy. The main findings of the study were: 1. In general, the study sample lacked the essential knowledge regarding drug intake during pregnancy especially in relation to the risk time for taking drugs in which nearly one-fifth of the sample (19.5%) did not know that it is risky to take drugs during pregnancy without doctor's order. 2. Regarding the practices of the study subjects in relation to drug intake during pregnancy, it was observed that the majority of the sample (86%) took drugs without prescription such as vitamins and general tonics, antacids, analgesics, anti-emetics, sedatives and antibiotics to treat their minor or major complaints during pregnancy. 3. In this study, it was also found that certain factors seemed to affect women's knowledge regarding drug intake during pregnancy. It was more obvious to observe that nearly two thirds (60.8%) of women whose age was less than 30 years were more likely to have inadequate and poor knowledge in this respect. It was observed that the majority (81.9%) of illiterate women were more likely to have inadequate and poor knowledge about drug intake during pregnancy. It was also found that nearly three quarters (72.3%) of housewives were more likely to have poor and inadequate knowledge. It was also noticed that the majority (81.5%) of the primigravidae women were more likely to have poor and inadequate knowledge. It was also noted that the majority of women (87.1%) who had previous abortions were more likely to have poor and inadequate knowledge. PMID- 7775882 TI - Phosphorus-nitrogen loading and trend of fish catch as index of lake Mariut eutrophication. AB - Lake Mariut was considered in the past to represent an important source of fish production in Alexandria especially during the periods which were characterized by low catch from its marine fisheries. The growing population in Alexandria and the expanding industries around the lake were accompanied with increased quantities of domestic and industrial wastes discharged annually into the lake proper. These quantities were increased from 192 million cubic meters in 1974 to about 300 million cubic meters in 1992. Consequently, the water quality in this basin was highly deteriorated and changed to become markedly eutrophic. High input of nutrients through sewage and industrial wastes has considerably increased the phosphorus and nitrogen load in the lake proper. Phosphorus and nitrogen loading in this basin were estimated in 1992 to be 60.2 gm/m3 P/y and 79.8 gm/m3 N/y. According to the nutrient concept given by Vollenweider (1974), these two figures have provided an evidence that the lake proper was strongly changed from oligotrophic to polytrophic phase. The trend of its total fish catch as well as the trend of different fish categories catch during the period 1970 1992 also confirms its eutrophication. This is in addition to bad changes that took place with respect to environmental conditions due to the continuous inflow of domestic and industrial wastes from different sources into this part of Mariut lake. Marginal increments of the lake proper total catch were decreased from 20.6% in 1970 to -28.8% in 1992, while the marginal increments of Tilapia sp., Clarias sp, Anguilla sp. and Mugil sp. were decreased from 21.4%, 14.3%, 29.8%, and 28.9% respectively in 1970 to -29.1%, -25.3%, -43.0%, and -36.8% in 1992. Based on these two indices of the lake proper eutrophication, the expected improvement of its environmental conditions will take several years after treating all inland discharges flowing into the lake and/or diverting all relevant outfalls away from this basin. PMID- 7775884 TI - A prospective study of postoperative fever--a clinical epidemiologic study. AB - During a 12 months period 693 patients undergoing surgical procedures were prospectively studied to investigate the etiology of postoperative fever. The overall rate of fever was similar for the three categories of surgical procedures studied. No cause of fever was found in 5%, 2.7% and 1.7% of patients who underwent clean, clean contaminated and contaminated surgical procedures. PMID- 7775885 TI - Measurement of non-specific antibodies in renal transplant patients and the incidence of certain postoperative viral infections. AB - In this study we assess the level and incidence of panel reactive antibodies which are the main cause of hyperacute rejection in renal transplant. The patients sera were tested against the lymphocytes of standard individuals. The lymphocyte panel had adequate representation of most of known antigens. 11 out of 20 patients (55%) gave positive standard panel test utilizing the microlymphocytotoxic assay. The positivity was recorded at 20 degrees C suggesting that those patients were sensitized. When the recipient sera were treated with Dithiothreitol (DTT) 2 cases showed false cytotoxic antibodies as shown in the negative panel obtained after the DTT treatment. The other nine positive cases showed true cytotoxic by not reacting with DTT. 80% of active CMV infections occurred concomitantly to acute rejection episodes and/or its treatment, suggest a chronologic, possibly causal link between rejection and CMV infection. PMID- 7775883 TI - Epidemiological evaluation of oral polio vaccine efficacy in Cairo. AB - A case-control study was conducted between November 1992 and May, 1993 to assess the effectiveness of routine oral polio vaccine (OPV) immunization against paralytic poliomyelitis among children aged 1-5 years in Cairo city. Cases of paralytic poliomyelitis at Imbaba Institute of poliomyelitis and Ain-Shams Pediatric Hospital fulfilling the study criteria were obtained. The diagnosis of cases was based on clinical grounds. Age and sex-matched controls were recruited concurrently from patients admitted for reasons other than poliomyelitis. There were 55 cases of poliomyelitis. Vaccination status of cases and controls was ascertained by asking the mothers through interviewing using a questionnaire that had been developed for the purpose of the study. Vaccine efficacy (VE) was 86% (95% CI: 39-97%) and 92% (95% CI: 64-98%) for 3 and 4 doses of OPV respectively. For a vaccine like OPV with the potential of near 100% VE after 3 doses, the estimated level of protection (86%) is considered low especially when we realize the enormous efforts carried out by Ministry of Health and UNICEF in Egypt for upgrading the cold-chain. Higher figures of VE are supposed to be achieved if we are going to meet the challenge of poliomyelitis eradication by the year 1994. Potential biases in study design were also discussed. PMID- 7775886 TI - Study of behavioral pattern among preschoolers in Alexandria. AB - A cross sectional study was done on (178) preschooler selected in a cluster technique. Matthews Youth Test of Health was completed by teachers for measurement of (type A) behavior pattern. (BCL) was chosen to assess behavioral problems among preschoolers. (type A) children in the study constituted 43.82% and those having behavioral problems were 29.21%. Boys were significantly more of (type A) and had more behavioral problems than girls (X2 = 4.9012 and 6.1730 respectively). Professional parents had children significantly more of (type A). Single children were significantly more of (type B). Children tended to be significantly more (type A) when their both parents were (type A). PMID- 7775887 TI - Influence of different means of washing and processing on removing of Actellic residue from spinach and eggplant and its in-vivo action on mice hepatic biochemical targets. AB - This study was carried out to investigate the effect of different washing solutions on the removal of Actellic residue from fresh and processed vegetables, namely; spinach and eggplant. Also, to identify the effect of Actellic residue on the health status of mice when fed these contaminated vegetables. The amount of insecticide residue detected using GLC indicated that, tap water, sodium hydroxide solution and potassium permanganate solution gave high percent removal. However, processing did not remove more than 45% except for grilling of eggplant which removed 88.17%. Meanwhile, changes in some hepatic biological parameters were well recognized in the groups of mice fed contaminated- unwashed either processed or unprocessed vegetables. PMID- 7775888 TI - A method for adjusting the international growth curves for local use in the assessment of nutritional status of Saudi pre-school children. AB - The aim of this study is to illustrate a method for adjusting the internationally used National Center for Health Statistics (NCHS) growth curves for local use in the assessment of nutritional status of Saudi children. All children 1-60 months in three semiurban-rural communities in Asir region, Saudi Arabia (N = 1168) were subjected to weight and height (or length) measurements. These measurements were individually compared with those of the NCHS reference population. The distribution of the study population was found to be significantly shifted to the left of the normal distribution for reference population on the percentile growth curves (P < 0.001). This denoted the inappropriateness of the NCHS reference standards for local use. Accordingly, the lower limits for the expected normal on the growth curves has been shifted from the 3rd percentile line to -3 standard deviation line, to be suitable for the Saudi children. This led to 70% & 56% reductions in the estimation of undernutrition, based on wt/age and ht/age indicators respectively. It is recommended that this adjustment be supported by other studies locally and in other developing countries. PMID- 7775889 TI - Hearing impairment: is it a public health problem among primary school pupils in Alexandria? AB - A hearing screening survey was conducted among the primary school students in Alexandria. It aimed at measuring the prevalence of hearing impairment among students and studying the predisposing factors of hearing problems. The schools of the middle educational region were selected to carry out the study. Hearing tests; audiometry and tympanometry, were used to screen 196 students from different types of schools (113, 55 and 28 students from governmental, language and private schools respectively). A questionnaire was introduced to a subsample of those students (n = 141) including some predisposing factors of hearing problems and answered by parents. The physical environment of schools was studied including noise level, ventilation and crowding. The obtained results showed that the prevalence of failed students in audiometry and tympanometry was 24.49 % and 36.22 % respectively. Moreover, the prevalence of pupils who failed in both tests was 7.65 %. Boys were more likely to have hearing impairments than girls. Positive family history of deafness early in life and the continuous complaining of nasal obstruction were significantly related to hearing impairments among students. A very small percentage of parents (4.17 %) were aware of the presence of a hearing problem in their children. Furthermore, 48 % of failed students in audiometry were poor achievers in schools as stated by their teachers. The study of physical environment in schools revealed noise levels (inside and outside classes) above the acceptable but still within the permissible level. On the other hand, crowding at schools, as measured by the per capita space area, showed a significant association with the hearing problems in students. It is recommended to improve awareness of parents and teachers through health education programs. Screening questionnaire can develop an at risk concept for children, as the use of specialist otologists for screening is likely to be very expensive and they must be considered as first point of referral after screening. PMID- 7775892 TI - Prevalence of amblyopia among schoolboys in Abha city, Asir Region, Saudi Arabia. AB - The aim of this study is to estimate the prevalence of amblyopia among schoolboys in Abha City and to examine its relations with anisometropia and strabismus. A total of 971 male school children were selected randomly from the elementary schools for male in the city. Using the criterion of a visual acuity of 6/9 or worse, with no obvious structural disease of the eye, to define amblyopia, 18 cases have been found to have the condition, with a prevalence of 1.85%. Those cases consisted of 7(47%) with anisometropic amblyopia and strabismus, and 2(13%) with deprivation amblyopia. Amblyopia showed a prevalence equal to 27% and 31% among children with anisometropia and those with strabismus respectively. An effective screening program for early detection of amblyopia through the well baby clinics is recommended. PMID- 7775890 TI - An audit of caesarean section among Saudi females in Jeddah, Saudi Arabia. AB - In this study the case records of 1414 patients who delivered at Alshaty hospital within one year were examined and some important variables related to caesarean section cases and their outcome were discussed. The caesarean section rate was found to be 9.9%. The high number of grand multigravida and primigravida among these Saudi mothers have contributed to this high caesarean section rate. The high emergencies in these sections (73.6%) have resulted in higher incidence of maternal and fetal morbidity namely postoperative pyrexia (37%), maternal anemia (20%) and extensive neonatal resuscitation (34%). The main indications of caesarean section in this hospital were repeated caesarean section (34.3%), failure of progress (19.3%) and fetal distress 12.9%. The relation and interaction between the three groups were thoroughly discussed based on the mechanisms of these indications. It is concluded that the changing trend of indications of caesarean section was mostly related to the change in departmental management rather than change in the characteristics of the patients. PMID- 7775891 TI - Study of the knowledge, attitude of Egyptian health care workers towards occupational HIV infection. AB - Acquired immuno-deficiency syndrome (AIDS) was reported for the first time in Egypt in 1986. Up to March 1993, 60 cases were notified to the Ministry of Health and 359 were detected to be infected with human immunodeficiency virus (HIV). Most cases had acquired infection abroad through blood, blood products or sexual contact. The number of cases is continuously increasing. Fear and ignorance about HIV infection causes panic among health care workers (HCWs) whenever a case is discovered and needs medical care. We assessed the knowledge and attitude of 346 HCWs towards the probability of occupational HIV infection using a self administered questionnaire. The sample included physicians, surgeons, nurses, laboratory technicians and ambulance workers. 72.8% of HCWs believed that they are in "great" danger of acquiring AIDS through occupational exposure, whereas 0.6% thought that there was no danger. 67% of HCWs had wrong ideas about transmission of HIV (toilet seats, droplet infection, touching patients). 83.5% mentioned that AIDS patients should be isolated in quarantine. The main source of information about AIDS was the television, radio and ordinary press. 44.8% got their information from textbooks or scientific literature. 95.4% felt the need for more information about infection and disease. The results show an urgent need to start a program of education of HCWs concerning the risk of occupational HIV infection and the measures of its prevention. PMID- 7775893 TI - The evaluation of an Arabic version of Rose questionnaire. AB - An Arabic version of Rose questionnaire was tested to establish its credibility as an epidemiological tool for screening purposes. The study showed that the criteria used in defining CHD determinants were still applicable today and in Arabic. The Arabic version maintained similar, if not better, sensitivity and specificity results than its original counterpart. The study pointed out, however, to several limitations that should be kept in mind during the interpretation of the questionnaire results. PMID- 7775894 TI - Anticardiolipin antibodies in rheumatoid arthritis. AB - The presence of anticardiolipin antibodies (aCL IgM & IgG), rheumatoid factor (RF) C-reactive protein (CRP) and antinuclear antibodies (ANA) were evaluated in 26 patients with rheumatoid arthritis (RA) disease [12 patients with acute disease (gr 1), 14 patients with chronic disease (gr 2) and 10 normal subjects as control (gr 3)]. aCL IgM was significantly increased in gr 1 & gr 2 when compared with gr 3 (P < 0.001 & P < 0.010 respectively). aCL IgG was non significantly increased in gr 1 & gr 2 when compared with gr 3 (P < 0.076 & P < 0.022 respectively). In group 1 75% of the patients were positive for a CLIgM, 25% positive for a CLIgG, 75% for RF, 58.3% for CRP, 25% positive for ANA Shaggy pattern and 33.3% positive for ANA speckled pattern. In group 2, the percent of positive cases were 42.85% for a CLIgM, 14.28% for a CLIgG, 42.8% for RF, 57.14% for CRP, 14.25% for ANA shaggy pattern and 28.57% for ANA speckled pattern. In the control group, all antibodies proved to be negative in every case. There was positive correlation between a CL IgM & aCLIgG and duration of disease in gr 1 & gr 2. There was positive correlation between a CLIgM and ESR in gr 1. There was negative correlation between a CLIgG and ESR in gr 1. There was negative correlation between a CLILgM & ESR in gr 2. There was positive correlation between a CLIgG & ESR in gr 2. We conclude that the presence of a CL antibodies (IgM & IgG) correlate well with the activity of disease, so this draw our attention to the importance of a CL antibodies as a parameter for prognosis of the disease. PMID- 7775895 TI - Referral system in the Asir Region, Saudi Arabia: knowledge, attitude, and practice of physicians working in urban areas--a comparative study of governmental and private health sectors. AB - A comparative study of knowledge, attitude and practice regarding referral system was undertaken among all governmental primary health care and private dispensary physicians (56 and 50 respectively) in Abha and Kamis, Asir Region. Results show that knowledge about referral is adequate in both groups, but the attitudes and practice of both groups need to be positively modified specially among the private sector physicians. The paper recommends more orientation programs for both groups of physicians and urges the private sector physicians to be more involved in Ministry of Health training programs and activities. Cooperation in referral between the private sector and government hospitals is seen as one way of improving health care in Saudi Arabia. PMID- 7775896 TI - Prevalence of antibodies to Toxoplasma gondii among blood donors in Abha, Asir Region, south-western Saudi Arabia. AB - One thousand samples of sera from healthy blood donors in the Asir Central Hospital, a tertiary facility in the Southwestern part of Saudi Arabia, were screened for Toxoplasma gondii IgG antibodies by the Indirect Haemagglutination Antibody (IHA) test. A prevalence of 52.1% was found. Seropositivity increased with age. The Geometric Mean Titre (GMT) of IHA antibodies was 596.7. While the prevalence increased with age, the GMT declined in the higher age groups. Three hundred sixty six of these sera were also tested for specific IgM titres by micro ELISA technique and 4.1% were found positive, indicating possible acute or recent infection. These serological studies indicate a higher prevalence of toxoplasmosis among healthy blood donors in the Asir region compared to earlier seroprevalence studies in other areas of Saudi Arabia. The high frequency in antibody titres might be due to differences in climatic conditions, culinary habits and exposure to the sources of infection. In view of these findings, it is felt that when considering blood transfusion for a special group of patients (i.e. immunocompromised or immunosuppressed), it would be wise to exclude those with evidence of previous exposure to T. gondii. PMID- 7775897 TI - Study of referral process between general practitioners and specialists in health insurance clinics in Alexandria. AB - The present study was designed to investigate the reasons for which patients are referred by G.Ps to G.M. specialists, and to assess the extent to which referred cases need specialist care. The study sample included specialists of general medicine working at 4 of the H.I.O. polyclinics and all G.Ps who referred cases that were considered as inappropriate referrals by the study specialists, as well as 20% of Patients referred to G.M. specialists by G.Ps. were systematically randomly selected during a period of 10 consecutive days. The results indicated that the rate of inappropriate referral to G.M. specialists was high, the rate of discrepancy between G.P. and specialist diagnoses was generally high, there was a high discrepancy between G.Ps and specialists regarding the reason for inappropriate referral, and there was poor communication from the lower (G.P.) to the higher (specialists) levels in the referral process. Reasons for referral to specialists were not recorded by G.Ps in 100% of cases. To overcome these problems H.I.O. should place special emphasis on the professional training and continuing education of G.Ps, with special attention to the few common conditions that were responsible for the greater proportion of referral problems. At the same time, H.I.O. should strengthen the technical and administrative control over G.P. referral behavior. PMID- 7775898 TI - Alternative therapies. PMID- 7775899 TI - Screening flexible sigmoidoscopy and insurance reimbursement. PMID- 7775900 TI - Nebulized saline and bronchitis. PMID- 7775901 TI - Specialty choice by medical students. PMID- 7775902 TI - Revolution in the American medical system. PMID- 7775903 TI - Promotes diazepam as safe, effective. PMID- 7775906 TI - More medical malapropisms. PMID- 7775905 TI - Drug interaction induces hypoglycemia. PMID- 7775904 TI - Semen responsible for fishy vaginal odor. PMID- 7775907 TI - The complete annual physical examination refuses to die. PMID- 7775908 TI - Periodic health evaluation of adults: a survey of family physicians. AB - BACKGROUND: The routine periodic health evaluation (PHE) is a popular format in primary care practice for the delivery of clinical preventive services to adults, but knowledge of the current pattern of use and of the content of the PHE is limited. METHODS: We surveyed a random sample of 567 family physicians (response rate, 60.1%) in New England regarding their approach to and attitudes about the PHE of adults. RESULTS: Family physicians reported spending a mean of 35.2% (11.6 hours per week) of their total ambulatory care time on adult PHEs, which were usually scheduled for 20 to 30 minutes each. All respondents recommended a PHE to men > or = 50 years old and to women > or = 40 years old, and more than 90% recommended a PHE to younger patients. Most physicians (80.7%) reported that the PHE is their primary mechanism for delivering preventive services, and 90.6% believed that the PHE should include a comprehensive physical examination. The mean number of physical examination items performed during the PHE was 11.6 to 13.9, depending on patient age and sex. As part of the PHE, most physicians (71.6% to 90.7%, depending on patient age and sex) ordered one or more screening laboratory tests not recommended by the US Preventive Services Task Force. Utilization of fewer laboratory tests was associated with residency training, employment in a health maintenance organization (HMO), and limited concern about malpractice suits. CONCLUSIONS: Family physicians reported spending a substantial amount of time on the PHE of adults, performing extensive screening physical examinations and many screening laboratory tests of unknown effectiveness. Among family physicians, there is considerable unexplained variation in the form and content of the PHE. PMID- 7775909 TI - Including smoking status as a new vital sign: it works! AB - BACKGROUND: Despite the adverse health consequences of smoking, many physicians still neglect to counsel smokers to quit. This study evaluated the effect of including smoking status as a vital sign on the frequency of physician discussions with patients about smoking and physician advice to quit smoking. METHODS: A consecutive sample of adult ambulatory patients in our metropolitan family practice residency program completed exit surveys on physician and nurse counseling about smoking. Control group data were collected for 1 month before the change was made to include smoking status as a vital sign on patient charts. Charts were then marked with a stamp as a chart prompt in the vital signs section. Data were collected for 2 months after smoking status was added to the stamp. RESULTS: There were 637 individuals surveyed, of whom 179 were current smokers; 95 in the "prestamp" group and 84 in the "poststamp" group. The percentage of patient-physician encounters during which smoking was discussed increased from 47% to 86% (P < .001). Physician advice to quit increased from 50% to 80% (P < .001). Physician discussion of smoking with patients increased across all of the five stages of change but most dramatically (53% to 95%) in the "preparation" stage. Physicians were much less likely to counsel patients in the "precontemplation" stage to quit smoking. CONCLUSIONS: Including smoking as a new vital sign significantly increased the likelihood of smoking-related discussions between patients and their physicians. The stamp is inexpensive and easy to use, and because it is a one-time office system change, it is more likely to be implemented and maintained in busy practices. PMID- 7775910 TI - Counseling patients for smoking cessation. PMID- 7775911 TI - Effect of race on survival following in-hospital cardiopulmonary resuscitation. AB - BACKGROUND: Race has been shown to be a significant predictive factor in a number of treatment decisions and outcomes, including survival following out-of-hospital cardiopulmonary resuscitation (CPR). The goal of this study was to determine whether race is associated with the rate of survival to discharge following in hospital CPR. METHODS: Consecutive adult patients undergoing attempted CPR at three teaching hospitals were identified. Demographic, clinical, and laboratory data from the time of admission, information about the resuscitation attempt, and the outcome of CPR were recorded for each patient. The characteristics of black and non-black patients were compared. Logistic regression was used to determine whether race was a significant independent predictor of CPR outcome. RESULTS: A total of 656 patients were identified. Black patients had a higher mean severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) III score, were more likely to have an initial rhythm of electromechanical dissociation or asystole, were less likely to have an admitting diagnosis of myocardial infarction or a history of coronary artery disease, and had a higher serum creatinine level, lower serum albumin value, and lower 24-hour urine output for the first 24 hours. There was no difference between black and nonblack patients regarding the rate of survival of the resuscitative effort itself. However, black patients were significantly less likely than nonblack patients to survive to discharge following resuscitation (Mantel-Haenszel odds ratio, 0.31; 95% confidence interval, 0.15 to 0.68). This relationship persisted after adjusting for potential confounders such as age, sex, initial cardiac rhythm, diagnosis of pneumonia, serum creatinine level, hospital, and APACHE III score. CONCLUSIONS: Black race is significantly associated with a lower rate of survival to discharge following in-hospital CPR. Further work is needed to explore this association in other settings; to examine the effect of other possible confounding variables, such as tobacco use, socioeconomic status, and marital status; and to further study the determinants of physician decision making about resuscitation. PMID- 7775913 TI - Laparoscopic general surgery: state of the art. AB - The rapid acceptance of laparoscopic cholecystectomy into surgical practice has been followed by the extension of laparoscopic treatment to many other surgical problems. While the role of laparoscopic surgery for some conditions is now well established, its applicability in other situations requires further evaluation. This review summarizes our current understanding of the laparoscopic management of common surgical disorders involving the gallbladder and bile ducts, groin hernias, appendix, colon, stomach, and esophagus. PMID- 7775914 TI - A case report of disseminated blastomycosis and adult respiratory distress syndrome. AB - Blastomycosis is a fungal disease endemic to the midwestern and southeastern United States. This is a case report of a 29-year-old woman who presented with weight loss, fever, fatigue, and pneumonia. She developed disseminated blastomycosis, adult respiratory distress syndrome (ARDS), and ulcerative skin lesions, requiring mechanical ventilation, amphotericin B, and multiple surgeries. Blastomycosis is endemic to a large portion of the United States. Family physicians should consider fungal infection in the differential diagnosis of an unresolving pneumonia. PMID- 7775912 TI - Effect of terbutaline tocolysis on infant birthweight. AB - BACKGROUND: Previous research has suggested that terbutaline sulfate increases serum glucose in pregnant women. Increases in serum glucose in women who have gestational diabetes mellitus often lead to the birth of larger infants. This study examines the effect on infant birthweight of terbutaline used as a tocolytic agent in otherwise normal term pregnancies. METHODS: An historical cohort study was conducted of all births in a 12-month period at a US Army community hospital. There were 1376 deliveries of all types; 481 of the patients were excluded for variables that influence gestational duration or fetal weight, and 5 patients' records were lost. Birthweights relative to gestational age were compared. RESULTS: The two groups (women who were treated with terbutaline, n = 94; control group, n = 796) differed with respect to age (terbutaline group, 1.6 years younger, P = .002); pregravid weight (terbutaline group, 10.3 lb lighter, P < .001); and total weight gain (terbutaline group, 3.2 lb less, P = .001). The groups were comparable in all other variables studied (P > .05). Women receiving terbutaline therapy (average length of therapy, 4.7 weeks) gave birth an average of 1 week earlier than those not treated with terbutaline (39.09 weeks and 40.09 weeks, respectively, P < .001). The mean absolute birthweight of infants exposed to terbutaline in utero was less than that of infants from the control group (P < .001), but this difference (191.6 g) can be accounted for by the difference in average gestational age between the terbutaline group and the control group. There was no difference in birthweight (P > .05) when birthweight relative to gestational age was compared between the two groups. CONCLUSIONS: Women in this study who were treated with terbutaline did not give birth to larger infants. The previously noted hyperglycemia in women receiving terbutaline may not have been present in this study population or may not have been significant enough to affect birthweight. PMID- 7775915 TI - Urinalysis to diagnose UTI. PMID- 7775916 TI - Efficacy of screening mammography. PMID- 7775917 TI - Use of the periodic health evaluation by family physicians. PMID- 7775918 TI - A feel for the water. PMID- 7775919 TI - Competing in the managed care milieu. PMID- 7775920 TI - Above the law. PMID- 7775921 TI - The medical examiner. When to report and help with death certificates. AB - Medical examiners perform autopsies on victims of criminal violence and such deaths must be reported to the medical examiner. Because few medical personnel are cognizant of the full extent of the types of deaths which must be reported and of the substantial noncriminal aspects of medical examiner services, this description of the Florida Medical Examiner System emphasizes these areas and deaths due to late sequelae of violence. Proper death certification is one aspect of medical practice in which most physicians receive absolutely no training; therefore the essential elements are briefly outlined. PMID- 7775922 TI - Rupture of symphysis pubis caused by forceful and excessive abduction of the thighs with labor epidural anesthesia. AB - Only a few cases of rupture of the symphysis pubis have been reported but the condition could become more frequent with epidural anesthesia. Conservative management is emphasized. Rupture is caused by desensitization to the labor process due to epidural anesthesia and excessive abduction of the thighs to increase anterior-posterior diameter during the birth process. Greater use of labor epidural anesthesia could increase the frequency of this event. PMID- 7775923 TI - Physician issues and Florida health care reform. AB - Data are presented from a mail survey of Florida physicians one year after passage of the Florida Health Care Insurance and Reform Act. Respondents rated the importance of various issues and reported their perceptions of physician input, knowledge and support for health-care reform legislation. Issues considered important included tort reform, physician autonomy, consumer choice of providers, and freedom from insurance hassles along with reduced paperwork. Ratings were low for input and health-care reform support. Issues of importance to physicians were not addressed by previous legislation; therefore, they must take the lead in focusing new legislation in conjunction with their professional organizations. PMID- 7775924 TI - Cyber documentation. PMID- 7775925 TI - Power of negative thinking. PMID- 7775926 TI - Resisting the reality of the HIV/AIDS epidemic. PMID- 7775927 TI - The FMA's on-line system. PMID- 7775928 TI - Differentiation of vaccine and wild mumps viruses by polymerase chain reaction and nucleotide sequencing of the SH gene: brief report. AB - The nucleotide sequences of the SH gene and its F gene flanking region were determined over a range of 322 nucleotides for two live vaccines, two vaccine associated isolates, six wild mumps viruses, and an attenuated mumps virus and compared to other sequences already published. Comparison revealed that the vaccine strains were clearly different from each other and the postvaccination isolates were different from the vaccines used. The viruses were assigned to three known cocirculating viral lineages. The attenuated mumps virus possesses nucleotide sequences identical to those of its progenitor strain. PMID- 7775929 TI - Adenovirus genome types isolated from stools of children with gastroenteritis in Sao Paulo, Brazil. AB - In a prospective one-year study of acute gastroenteritis in hospitalized children less than 2 years of age, in Sao Paulo (Brazil), adenoviruses were detected by specific enzyme immunoassay (El-ARA) in 7 of 67 (10%) ill children and in 9 of 79 (11.4%) controls. They were the sole recognizable agent of diarrhea in 6 ill children. In another child these viruses were detected in a dual infection with astrovirus. Enteric adenoviruses (Ad40/41) were the most common serotypes detected in children with diarrhea (3/7) and Ad7 the serotype most detected in the controls (5/9), associated with lower respiratory tract infection. Thirteen adenovirus strains, isolated in HEp2 or HEK-293 cells, were characterized by seroneutralization and restriction enzyme analysis. The established adenoviruses were typed as AV-7-D5 (five associated to lower respiratory tract infection and one to diarrhea), AV-1-D10 (one diarrhea case), AV-31-D2 (two controls with respiratory infection), and two isolates as AV-12-D7, a new genome type. One subgenus D isolate, serotype 28, with restriction patterns different from those of the prototype, remained untyped. Only one enteric adenovirus could be typed. The restriction patterns of this isolated were similar to those of the prototype AV-41-D1. The genome type of the other three enteric adenoviruses could not be determined. PMID- 7775930 TI - Detection and characterisation of bisegmented double-stranded RNA viruses (picobirnaviruses) in human faecal specimens. AB - The prevalence of picobirnaviruses (PBVs) in human stools was investigated by polyacrylamide gel electrophoresis (PAGE) analysis of 832 faecal specimens collected between 1982 and 1993 from patients in various clinical groups. Similar prevalences (9-13%) were detected in patients with or without gastroenteritis and throughout the age range of 3 to > 65 years. Two methods for the extraction of nucleic acid, a phenol/chloroform method and a guanidinium thiocynate (GTC)/silica method, were compared. Detection of PBVs by PAGE was three times more sensitive following RNA extraction by the GTC/silica method. Characterisation of three strains was carried out. Segment sizes ranged from 1.625 to 1.95 kilo base pairs (Kbp) and 2.2 to 2.5 Kbp for the fast and slow migrating bands, respectively. The nuclic acid was shown to be double-stranded RNA (dsRNA) by nuclease digestion. PBV-like particles were detected by electron microscopy in two PAGE-positive stools. Virion diameters ranged from 35 to 41 nm and a buoyant density of 1.38-1.4 g/ml in caesium chloride (CsCl) was demonstrated. These findings suggest that PBVs are widespread in humans in the United Kingdom. However, no disease association could be demonstrated. PMID- 7775931 TI - Hepatitis C virus RNA in plasma and blood mononuclear cells in patients with chronic hepatitis C treated with alpha-interferon. AB - Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with alpha-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.8% of PBMC. After 3 months of treatment, HCV RNA was still present in 63.6% of plasma samples but in only 27.3% of PBMC. A good correlation was observed between serum alanine aminotransferase level normalisation and disappearance of the viral genome in plasma. Among the six responder patients, five relapsed shortly after IFN withdrawal; HCV RNA became detectable again, especially in PBMC. These results show the presence of HCV in PBMC from most patients infected chronically. IFN therapy had an inhibitory effect on viral replication in lymphoid cells, but frequent relapses observed after cessation of treatment with IFN suggested persistence of HCV in these cells. PMID- 7775932 TI - Comparison of the kinetics of Puumala virus specific IgM and IgG antibody responses in nephropathia epidemica as measured by a recombinant antigen-based enzyme-linked immunosorbent assay and an immunofluorescence test. AB - Immunoglobulin M and G (IgM and IgG) responses were followed up to 6 months in patients with nephropathia epidemica (NE) by an enzyme-linked immunosorbent assay (ELISA) using a recombinant Puumala virus (PUU) nucleocapsid protein as antigen and an immunofluorescence test (IF) using PUU infected, acetone-treated cells as antigen. The recombinant protein was produced by cloning and expressing the nucleocapsid encoding gene of PUU as a polyhistidine fusion protein in Escherichia coli. The product was purified over a metal chelating ion affinity column. On admission, all 17 patients had an IgM response by both methods. The IgM titers decreased significantly by both methods 3 months after onset (ELISA P < 0.05 and IF P < 0.05). Four of six still had detectable IgM, however at low levels, after 6 months. Presence of specific IgG differed significantly on admission between the two methods: by ELISA 8 of 17 had detectable specific IgG, whereas by IF 15 of 17 had specific IgG (P < 0.02). There were 10 significant titer rises between acute and convalescent serum samples in the same patients by both methods. It is concluded that the IgG antibody response differs in the early phase of NE as measured by a method using a recombinant PUU nucleocapsid protein and a method using PUU infected acetone-treated cells as antigens. Furthermore, the results suggest that it is of importance to rely on specific IgM for serodiagnosis of NE during the acute phase. PMID- 7775933 TI - Single-step nested polymerase chain reaction for detection of different genotypes of hepatitis C virus. AB - Hepatitis C virus (HCV) exhibits considerable sequence variability and circulates in the blood at extremely low levels. Current methods for detecting HCV RNA are based mostly on nested polymerase chain reaction (PCR), in which part of the first amplification product is reamplified in the second tube by an internal primer pair. A novel nested PCR method was developed in which the two successive amplification processes are carried out in the same tube with a single step of physical manipulation. Careful selection of highly conserved sequences of the 5' noncoding region as primers enabled successful detection of all three major genotypes circulating in France, including the one with variation in this region. Retaining high sensitivity of the conventional nested PCR, the novel method reduced greatly the risk of carry-over contaminations. It was also cost- and time saving. The one-step nested PCR method is especially suitable for routine diagnosis of HCV infection in clinical laboratories. PMID- 7775934 TI - Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue. AB - The serum of 88 chronic fatigue patients was screened for enteroviral specific sequences by polymerase chain reaction (PCR) assay. The PCR method used was "nested" PCR targetting the 5' nontranslated region of the enteroviral genome which yielded a final fragment length of 264 base pairs. Samples were obtained from patients during 1990-1991. In addition, buffy coat specimens and stool specimens were examined in some patients. Samples from two cohorts of comparison individuals were also obtained. The comparison groups were firstly, acutely ill individuals with symptoms consistent with a presumed enteroviral infection (matched by age, sex, and date of receipt of specimen) and secondly, healthy individuals (matched by age and date of receipt of specimen). Enteroviral specific sequences were detected in 36 of 88 serum samples from chronic fatigue patients, 22 of 82 acutely ill individuals, and 3 of 126 healthy individuals. The enteroviral PCR positivity did not correlate with any one particular feature of chronic fatigue nor did it reflect any history of illness at onset of fatigue, duration of fatigue, or age of patient. These results provide new evidence for the presence of enteroviral specific sequences in serum, buffy coat, and stool samples in many patients with chronic fatigue. This may reflect a persistent enterovirus infection in a proportion of chronic fatigue patients. PMID- 7775935 TI - Seroprevalence of hepatitis C virus infection and its genotype in Lanzhou, western China. AB - The seroprevalence of hepatitis C virus (HCV) infection in Lanzhou, Western China was studied. HCV genotypes in 20 patients with HCV infection was determined by genotype-specific primer for polymerase chain reaction (PCR) based on HCV core region and compared with the genotype assigned by sequence comparison and molecular evolutionary analysis based on the same region. Antibody to HCV (anti HCV) was present in 2.5% of volunteer blood donors and in 35.0% of paid blood donors (P < 0.01). HCV infection is uncommon in patients with liver disease who attended liver clinics in this locality; 4.0% with acute hepatitis and 4.0% with chronic hepatitis, 10.0% with liver cirrhosis, and none with hepatocellular carcinoma were seropositive for anti-HCV. Genotype 1b and 2a were both found to be prevalent. Together, they accounted for 19 of 20 (95%) patients with HCV infection. Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype-specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis. These data showed that HCV is present in Western China, HCV infection is more common in paid blood donors, and HCV genotypes 1b and 2a are both prevalent in Western China. PMID- 7775936 TI - Cytomegalovirus infection and viral shedding in the genital tract of infertile couples. AB - The prevalence of cytomegalovirus (CMV) infection and viral shedding in infertile couples in Taiwan and its role in infertility were studied. Two hundred fifty couples were enrolled in this study. Anti-CMV IgG was measured in serum samples from these infertile couples. Viral shedding examined by DNA hybridization was detected in semen from the husband and cervical mucus from the wife. Anti-CMV IgG was detected in 249 (99.6%) of the 250 male serum samples and in 247 (98.9%) of the 250 female serum samples. Viral shedding was detectable in 83 (33.5%) of 248 semen samples and 83 (33.7%) of 246 cervical mucus samples by dot-blot DNA hybridization assay. Semen quality was not apparently affected by the existence of viral shedding. The co-shedding rate in semen and cervical mucus was high (15.9%). It is concluded that the seroprevalence and genital tract viral shedding were relatively high in infertile couples in Taiwan. Viral shedding did not affect the semen quality. Nevertheless, screening of donor semen is recommended. PMID- 7775937 TI - Geographic sequence variation of latent membrane protein 1 gene of Epstein-Barr virus in Hodgkin's lymphomas. AB - To assess the role of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene in the development of Hodgkin's lymphoma (HL), the polymorphism of this gene in EBV isolates from different geographic locations was analyzed. A 497 bp fragment spanning LMP1 gene exons 1 and 2 was amplified by polymerase chain reaction (PCR), using a primer pair bracketing a Xhol restriction site. PCR products were subjected to Xhol digestion and to DNA sequencing analysis. Twenty five HL biopsy specimens from the United States and five HL and four non Hodgkin's lymphoma (NHL) biopsy specimens from Italy were examined. Eighty percent of LMP1-positive samples (12 of 15) from the United States maintained the Xhol restriction site and the remaining 20% partially lost the Xhol site. One of four EBV-positive HL and one of the three EBV-positive NHL specimens from Italy lost the restriction site. The other three EBV-positive HL DNAs were partially cut by Xhol. Direct DNA sequencing analysis revealed that those Italian samples not digested by Xhol were due to a G to C transversion at the first base of codon 18, resulting in the change of glycine to arginine. Those DNA samples partially cut by Xhol were due to a mixture of G/C at the same location. In contrast, those partially digested American HL DNAs had a mixture of G/T at the second base of codon 17.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775938 TI - Renal failure due to BK virus infection in an immunodeficient child. AB - We report a child with cartilage-hair hypoplasia and Hodgkin's disease who developed progressive renal failure and died following infection with a polyomavirus, BK virus. Renal biopsy showed interstitial inflammation, tubular atrophy, and intranuclear inclusions in tubular epithelium, with large numbers of papovavirus particles within the cells. BK virus infection was confirmed by polymerase chain reaction on renal biopsy material and in urine and the demonstration of a high titre of haemagglutination inhibition (HI) and IgM antibody to the virus in the patient's serum. This case emphasises the need to study in depth any unusual clinical manifestation in immunocompromised patients to delineate better the full clinical impact of less well-established pathogens such as BK virus. PMID- 7775939 TI - Polymerase chain reaction detection of small round-structured viruses from two related hospital outbreaks of gastroenteritis using inosine-containing primers. AB - Two outbreaks of gastroenteritis in the UK which occurred nine days apart at Lymington and Southampton hospitals were investigated. The clinical and epidemiological features of both outbreaks were characteristic of small round structured virus (SRSV) infection with rapid onset of diarrhoea and/or nausea and vomiting and propagation of the outbreaks by secondary spread. SRSV particles were observed by immune electron microscopy (EM) in 60% of faecal samples from both outbreaks and no other pathogens were detected. The index case for the second outbreak was a patient who was admitted with diarrhoea and vomiting after being discharged from Lymington hospital during the first outbreak. The possibility that the two outbreaks were caused by the same strain of SRSV was investigated by the polymerase chain reaction (PCR). New inosine-containing PCR primers were designed to amplify the RNA polymerase region of SRSV cDNA from genetic groups I and II. The PCR using the group II primers achieved a higher detection rate for SRSVs in faecal samples (68% of samples positive from both outbreaks) than immune EM. SRSVs were not detected using the group I primers or using conventional degenerate PCR primers. The nucleotide sequences of PCR amplicons from both outbreaks were identical providing molecular epidemiological evidence for the involvement of a single SRSV strain. Comparison of the RNA polymerase region of this virus with the equivalent regions of genetic group I (69.4-75.0% amino acid identify) and genetic group II (88.9-100% amino acid and 77.1-88.1% nucleotide identity) SRSVs revealed that the causative SRSV was a distinct member of genetic group II. PMID- 7775941 TI - Hepatitis C virus genotypes in Belgian hemophiliacs. AB - Hemophiliacs who have been exposed to unheated and/or dry heated pooled clotting factor concentrates are at a high risk of chronic hepatitis C. Serum HCV-RNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 58 hemophiliacs positive for anti-HCV antibodies, HCV-RNA was detected in 55 patients. Based on the results of PCR positivity, HCV genotyping was carried out using genotype specific probes and the dot blot hybridization assay: 2 patients were found to be infected with type 1a (3.6%), 31 patients with type 1b (56.4%), 8 patients with type 2 (14.6%), 6 patients with type 3 (10.9%), 1 patient with type 4, and 7 patients with double infection (12.7%). As compared to a control group of 105 nonhemophilia patients with chronic hepatitis C, HCV genotype 1b was found predominant in both groups. However, double infection with two HCV types as well as a relatively high prevalence of infection with type 2 and type 3 were found in hemophiliacs. PMID- 7775940 TI - Prognostic value of adenosine deaminase compared to other markers for progression to acquired immunodeficiency syndrome among intravenous drug users. AB - This study was designed to determine the prognostic value of erythrocyte adenosine deaminase (ADA) as a possible indicator of progression to AIDS, and compare this with other known cellular and serological markers. At the end of a 3 year study, a cohort of 114 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) from the five different Center for Disease Control (CDC) groups was examined in order to estimate the prognostic relevance with respect to the progression to acquired immunodeficiency syndrome (AIDS) of each of the following markers at baseline value: number and percentage of CD4+ T cells, number of CD8+ T cells, CD4+/CD8+ ratio, IgA and beta 2 microglobulin and ADA levels, and the presence of HIV antigens. Moreover, 57 IVDUs belonging to II and III CDC groups were analyzed in a follow-up study at 6-month intervals, in order to evaluate and compare the behavior of each marker over time. The prognostic significance of each marker was assessed by computing the survival distribution and the Cox analysis in a multivariate model providing the set of markers with greatest predictive value. The levels of ADA and the CD4+/CD8+ ratio showed a linear association with disease staging, whereas beta 2 microglobulin and CD4+/CD8+ ratio were the best predictors for AIDS progression. A highly significant increase in ADA and beta 2 microglobulin was observed during follow up. The results obtained among HIV-positive IVDUs clearly indicate that the erythrocyte ADA may be considered a reliable marker of the development of HIV infection from the intermediate stages of the disease onwards.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775943 TI - Detection of hepatitis C virus RNA in the cell fraction of saliva before and after oral surgery. AB - The presence of hepatitis C virus (HCV) RNA in serum, whole saliva, and saliva from the submaxillary glands was investigated before and after oral surgery. The presence of HCV RNA (positive and negative-strand RNA) was determined in serum and saliva by a nested polymerase chain reaction in 26 anti-HCV positive patients, of whom 11 were coinfected with human immunodeficiency virus-1. Oral surgery was carried out on five occasions on four of the patients. HCV RNA was detected in the sera of 23 of 26 (88%) patients, and in the saliva of 4 of the 23 (17%) of the viremic patients. In all four cases, HCV RNA was detected only in the cell fraction derived from centrifugation of whole saliva. Negative-stranded HCV RNA was not detected. At one of five occasions of oral surgery, HCV RNA was detected in saliva sampled immediately after surgery, but not before or 24 hours after surgery. The results suggest that HCV is present in saliva in less than 25% of HCV viremic persons. The presence of the virus in saliva is restricted to the cell fraction. Thus, saliva may serve as a possible, but low, nonparenteral transmission route of HCV. Contamination of saliva by blood during and after oral surgery may result in an increased risk of viral exposure. Except for trauma caused by sharp instruments during surgery, this might contribute to the higher HCV seropositivity found among dentists. PMID- 7775942 TI - Molecular characterization of a human calicivirus with sequence relationships closer to animal caliciviruses than other known human caliciviruses. AB - cDNA clones were produced from a morphologically typical human calicivirus (HuCV) in stool specimens collected in 1982 during an outbreak of gastroenteritis in Sapporo, Japan. The cDNA clones were generated separately in two laboratories by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers 35 and 36 derived from Norwalk virus. The RT-PCR product from six specimens was of the predicted size, had a continuous protein encoding frame on the positive strand, and contained GLPS and YGDD amino acid motifs at the predicted distance from the primers. RT-PCR amplification with primer 35 and a HuCV/Sapporo-specific primer 36 of four HuCV/Sapporo-positive stool specimens from a 1986 Houston day care center outbreak yielded products with 93% nucleotide and 99% predicted amino acid sequence identity with the HuCV/Sapporo strain from the 1982 outbreak. The HuCV/Sapporo strains are genetically distinct from previously characterized HuCVs and more closely related to known animal CVs than other known HuCVs. PMID- 7775944 TI - Measles antibodies in women and infants in the vaccine era. AB - The present investigation was done to determine whether measles enzyme immune assay (EIA) absorbency values were lower in women born in the vaccine era after 1963 and their infants in an upstate New York metropolitan area, an area of low measles incidence during the past 10 years compared with women born before the measles vaccine era who had natural measles. Aliquots of 202 sera from mother infant pairs collected for other purposes from November 1990 to June 1991 at Albany Medical Center Hospital were tested by EIA. The demographic data available for analysis were maternal age and infant gestational age. Measles mean absorbency values were analyzed according to maternal age. Of 202 mother-infant pairs, 30% of mothers and 17% of their infants were seronegative (EIA < 0.16). Mothers born before 1963 and their infants had significantly higher mean EIA absorbency values than mothers born after 1963 and their infants (P < 0.002). The percent seropositive for measles antibodies by EIA for mothers born before 1963 and their infants, 87% and 94%, respectively, was significantly higher than the percent seropositive for mothers born after 1963 and their infants, 61% and 69%, respectively (P = 0.0001). Since the mean measles antibodies as measured by EIA absorbency were significantly lower in the mothers born after 1963 and their infants compared with women born before the vaccine era, the strategy for measles control in the future may have to include lowering the age of infant immunization. PMID- 7775945 TI - Successful treatment of a squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. AB - Human papillomaviruses (HPV) are associated with benign lesions and show specificity towards the location or tissues that they infect. HPVs are responsible for warts. Among more than 60 different HPV types known to occur in humans, a strong association has been found between types 16 and 18 and cervical cancer, and such an association is also suspected for types 31, 33, 35, 45, 51, 52, and 56. We describe the effects of (S)-1-(3-hydroxy-2-phosphonyl methoxypropyl)cytosine (HPMPC), following local intratumoral injection, in a 69 year-old woman with hypopharyngeal and esophageal papillomatous lesions, polymerase chain reaction (PCR) positive for HPV types 16 and 18, that relapsed after surgery and that also failed to respond to Nd-Yag laser photocoagulation and alpha-interferon treatment (6 x 10(6) U five times a week for 4 weeks followed by three times a week for 2 months). HPMPC was given at 1.25 mg/kg, with a sclerosing needle, through the biopsy channel of a video-endoscope, directly into the tumor, from March until July 1993 at seven different occasions. The first four injections were given at an interval of 1 week at the level of the hypopharynx. The next three injections were given at an interval of 3 to 5 weeks. During the fourth to the seventh session, half of the dose was injected into the hypopharyngeal and the other half into the esophageal tumor. Three further injections of HPMPC were administered at the level of the esophageal tumor in September 1993 with 2-week intervals. After HPMPC treatment, the lesions became smaller and flat until they completely disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775946 TI - Complete nucleotide sequences and the characteristics of two hepatitis B virus mutants causing serologically negative acute or chronic hepatitis B. AB - Hepatitis B virus (HBV) DNA was amplified by the polymerase chain reaction from the sera of a patient with acute hepatitis and a patient with chronic hepatitis. Both patients were negative for serum hepatitis B surface antigen and hepatitis B core antibodies and had been previously diagnosed as non-A, non-B, non-C, non-D, non-E hepatitis. The nucleotide sequence revealed an 8-nucleotide deletion in the X-gene coding region creating a C-terminally truncated X protein, and probable mutation of the enhancer II/core promoter element. In addition, DR2 showed a T-to C mutation at the extreme 5'-terminus. These mutations within the X-gene coding region must suppress replication and expression of HBV DNA, and this seems to be responsible for absence of serological markers despite the presence of HBV infection. PMID- 7775947 TI - Analysis of genomic polymorphism among herpes simplex virus type 2 isolates from four areas of Japan and three other countries. AB - Genomic polymorphism of 307 epidemiologically unrelated strains of herpes simplex virus type 2 (HSV-2) from four areas of Japan and three other countries (Korea, Sweden and the U.S.A.) was analysed by using 16 variable markers selected from 97 restriction endonuclease (RE) sites with five REs. In addition to the 16 markers, 26 rare variable RE sites were found in 307 isolates. Five and four of 16 markers (RE sites) were found to differ in the frequency of isolates with the markers between isolates from Japan and Sweden and between those from Japan and the U.S.A., respectively, suggesting that they are genomically different from each other. In this manner, 307 HSV-2 isolates from four countries could be classified into 68 different genotypes (no. of isolates/no. of genotypes = 4.5). Some isolates from one country or more than two countries at times were classified into the same genotypes, which were referred to as predominant genotypes. The most predominant genotypes for isolates from Japan, Sweden and the U.S.A. were genotypes 30, 26 (32) and 3, respectively, indicating that they are different by the country. In genotypes 1 and 6, the frequency of isolates was found to be significantly different between Japan and Sweden and between Japan and the U.S.A., respectively. Nine out of 16 markers differed in the most genomically distant isolates, each of which was obtained in Sweden and Japan. In addition, high correlation coefficients (r) in the Japanese isolates were detected in different pairs of markers from those in the Swedish isolates, suggesting that isolates from these two countries are evolutionarily distant. PMID- 7775948 TI - Isolation of human herpesvirus 7 from an infant with febrile syndrome. AB - A viral isolate obtained from peripheral blood lymphocytes of an infant with a nonspecific febrile syndrome was identified as human herpesvirus 7 (HHV-7) on the basis of PCR analysis of its DNA with one set of primers specific for HHV-7. The correlation of HHV-7 with the febrile episode affecting the infant is suggested. PMID- 7775949 TI - Hepatitis C genotypes in haemophilic patients treated with alpha-interferon. AB - The effect of alpha-interferon on the hepatitis C genotypes was examined in 25 anti-HCV-positive haemophilic patients. The rate of multiple HCV genotypes in patients who are likely to have mixed infections was also studied. Pretreatment results showed that 3/25 (12%) patients had a change in genotypes, whereas posttreatment this rose to 10/25 (40%). Seven of 10 (70%) patients who showed a change in genotype had a clinical response to alpha-interferon. Six of 25 (24%) patients showed a complete clinical response to alpha-interferon, and the majority of these were either type 2 or 3. This study supports previous evidence that type 1 is less likely to respond to alpha-interferon, and that alpha interferon may alter the concentrations of the various circulating genotypes present in multiply-infected patients. There are many difficulties in studying hepatitis C in haemophilic patients due to the sequence heterogeneity within each individual, and this study has shown that no ideal method exists as yet for looking at HCV genotypes in multiply-infected individuals. PMID- 7775950 TI - Fulminant human herpesvirus six encephalitis in a human immunodeficiency virus infected infant. AB - Self-limited involvement of the central nervous system (CNS) is a relatively common complication of primary infection with human herpesvirus six (HHV-6) in normal children. We describe an HIV-infected infant who developed fulminant encephalitis as a complication of HHV-6 infection. Immunohistochemical staining of CNS tissue demonstrated productive infection of all CNS cell-types. Analysis of the infected brain tissue by the polymerase chain reaction (PCR) confirmed the presence of a dense HHV-6 infection in the tissue, and demonstrated that the virus present in the CNS tissue was predominantly the A variant of HHV-6. This is the first demonstration of invasive tissue disease caused by HHV-6 in an HIV infected infant. PMID- 7775951 TI - Detection and typing of human papillomaviruses by in situ hybridization with biotinylated oligonucleotide mixtures. AB - The value of biotinylated oligonucleotide probes for screening and typing by in situ hybridization of the most frequent genital human papillomavirus infections (HPVs 6, 11, 16, 18, 31, and 33) was assessed. Optimal hybridization conditions were defined on a panel of paraffin-embedded tissue sections previously characterized with HPV full genome probes. Mixtures of oligonucleotides rather than single oligonucleotides were used to improve sensitivity and specificity. All HPV-positive specimens were detected by the screening mixture with a sensitivity and specificity similar to that of full genome probes. Typing mixtures were highly specific for each HPV type. This study confirms the potential of oligonucleotide probes for detecting and typing HPV infections. PMID- 7775952 TI - Detection of acute measles infections by indirect and mu-capture enzyme immunoassays for immunoglobulin M antibodies and measles immunoglobulin G antibody avidity enzyme immunoassay. AB - An avidity test for measles IgG was developed and applied to the study of IgG immunoglobulin maturation kinetics in follow-up sera from 12 patients with known acute primary and convalescent measles and sera from blood donors. The avidity of the IgG anti-measles responses was measured using the 8 M urea elution technique, the results being expressed as the percentage ratio between the test readings for eluted and noneluted samples. The IgG avidity results were compared with those of indirect and mu-capture IgM enzyme immunoassays. This test was capable of detecting low-avidity antibodies at the acute phase of measles up to 7 weeks, and increasing avidity through immunosaturation during the convalescent phase. The avidity in these samples did not reach the level found in the samples of the blood donors under the follow-up time. Although a limited number of serum samples was examined, the results suggest that the measles IgG avidity test is a powerful tool for differentiating primary measles infection from the convalescent phase. PMID- 7775953 TI - Seroepidemiological study of hepatitis delta virus infection in Okinawa, Japan. AB - A seroepidemiological study on hepatitis delta virus (HDV) infection was conducted in the Okinawan islands, the area of Japan where hepatitis B virus infection is most prevalent. The subjects of this study included 116 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 48 patients with chronic hepatitis (CH), 19 with liver cirrhosis (LC), and 11 with hepatocellular carcinoma (HCC). Among the 194 serum samples examined, a total of 10 (5.2%) were anti-HDV seropositive. Anti-HDV was detected in 2 (1.7%) of the 116 asymptomatic HBsAg carriers, in 3 (6.3%) of the 48 patients with CH, and in 5 (26.3%) of the 19 with LC. However, none of the patients with HCC had detectable anti-HDV. Eight of the 10 were born in the Miyako island group and the remaining 2 on the main island of Okinawa. Since the subjects included 34 individuals who were living and/or born in the Miyako islands, the positive rate of anti-HDV in the islands was 23.5%. This study demonstrates the existence of an endemic area of HDV infection in Japan. PMID- 7775954 TI - Serological evidence for hepatitis E virus infection in Israel. AB - Israel is suspected to be endemic for hepatitis E virus (HEV) because of its geographic location and the large-scale immigration from endemic countries. Although no cases of local HEV infection have been diagnosed, a serological survey would provide indirect evidence for such infection. We examined sera from 1,416 healthy subjects, including 1,139 Jews from various regions of Israel and 277 Arabs, most of whom reside in the West Bank of the Jordan River. In addition, we tested 13 non-A, non-B, and non-C viral hepatitis patients. Sera were screened for antibody to hepatitis E virus (anti-HEV) by a newly developed enzyme immunoassay (EIA) and by immunoblots for both IgG and IgM anti-HEV activity. Positive samples were confirmed by neutralization. The seroprevalence found by EIA was 2.81% and 1.81% in the Jewish and Arab populations, respectively. More than a 2-fold higher prevalence in males compared to females and an increase with age were found in both populations. However, these differences were nonsignificant. The geographical distribution was even throughout the country, except for two clusters of 3 and 4 seropositive individuals possibly reflecting past foci of infection. Eight of 37 EIA-positive sera were positive for IgG, and 3 were positive for IgM by the immunoblot assay. Among hepatitis patients (9 acute and 4 chronic), one patient with chronic hepatitis was positive for both IgG and IgM. Our study provides indirect evidence that Israel is endemic for HEV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775955 TI - Precore and core mutations in HBV from individuals in India with chronic infection. AB - Ten hepatitis B surface antigen seropositive carriers (5 asymptomatic and 5 with chronic liver disease) were tested for HBeAg/anti-HBe and for HBV-DNA using the polymerase chain reaction. Five were DNA-positive, 2 with HBeAg and 3 with anti HBe. Nucleotide sequences were determined for these 5 cases. Hepatitis B virus DNA from one cirrhotic carrier with anti-HBe had a mutation in the precore region (nucleotide position 1862) which may affect signal peptide cleavage and HBeAg synthesis. In the other 2 anti-HBe- and DNA-positive cases, a cirrhotic carrier and an asymptomatic case, there was a mutation at nucleotide position 1896 leading to a termination codon in the precore region. In all 5 patients, except for one or two missense mutations, there was no significant variation in the core region. PMID- 7775956 TI - Seroepidemiology of hepatitis E in selected Australian populations. AB - The presence of hepatitis E virus-specific antibodies (anti-HEV) was determined in selected Australian groups. Anti-HEV was detected initially using a recombinant antigen-based enzyme immunoassay (EIA). It was found that 1 of 279 (0.4%) blood donors, 14 of 182 (7.7%) Indochinese refugees, 2 of 89 (2.2%) sera submitted for amoebic serology (generally people who had visited developing countries), 1 of 13 (7.7%) patients with non-A, non-B hepatitis, none of 7 (0%) patients with fulminant non-A, non-B hepatitis, and none of 33 (0%) control sera were repeatedly reactive by the HEV EIA. The positive sera were subjected to further testing using a supplemental immunoblot. Preliminary data suggest that while potentially large numbers of people infected with HEV are entering Australia, no compulsive evidence was found in these particular groups for endemic HEV infection in Australia. This is the first seroepidemiological survey of HEV in Australia. PMID- 7775957 TI - Local succession of adenovirus strains in pediatric gastroenteritis. AB - Assessment of the current incidence of different adenovirus types in local gastroenteritis involved the examination of over 1,000 stool specimens annually from 1988-1992. Adenoviruses were detected by electron microscopy and/or cell culture in 32% of the specimens in which a viral pathogen was detected. The identification of every adenovirus isolate to type by neutralization with specific antisera against the first 6 types and by restriction analysis of nonneutralized isolates was started in 1990. Samples from 1988 and 1989 were examined retrospectively. Adenovirus strains were compared to those isolated in a study between 1980-1983. Enumeration of individual adenovirus types revealed a number of trends, demonstrating that rapid changes in the local incidence of several strains were occurring in Manitoba. The incidence of adenovirus type 40 (Ad40) as a cause of gastroenteritis was found to have fallen dramatically in recent years. The predominant cause of gastroenteritis in Manitoba is a variant strain of Ad41, increasing in predominance each year and now responsible for over a third of the symptomatic cases examined since 1990. The majority of restriction site differences of the Ad41 variant strain from the prototype strain Tak were mapped to the hexon and fiber genes, both of which code for the neutralizable external viral epitopes. The probability of the observed pattern of mutations occurring by chance was calculated as P < 0.0005, indicating a strong pressure for selection of these immunologically significant alterations to the viral proteins responsible for cell attachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775960 TI - Analysis of clinical and virological factors associated with response to alpha interferon therapy in chronic hepatitis C. AB - Interferon alpha (IFN-alpha) therapy is currently the treatment of choice for chronic hepatitis C (HCV) infection, but it fails to achieve a sustained response in approximately 75% of those treated. The factors which determine whether or not an individual will respond to IFN-alpha are uncertain, although a number of potentially predictive factors have been proposed. In this study a wide range of clinical, demographic, and virological parameters were evaluated in relation to therapeutic outcome in a group of 30 Italian patients with chronic hepatitis C. All patients received 3 MU leukocyte-derived IFN-alpha three times a week for 6 months and were then followed prospectively for at least 12 months. 53% of patients responded initially, but a sustained response was observed in only 17%. Responders were found to be significantly younger than nonresponders (45.6 +/- 3.1 vs. 55.4 +/- 2.7), and less frequently cirrhotic (2/16 vs. 7/14). Sustained responders had a mean pretreatment HCV-RNA titer approximately tenfold lower than that of those who did not have a sustained response, but the difference was not statistically significant. HCV genotype was found to be significantly associated with both initial and sustained response. Patients infected with HCV-2a were more likely to respond (89%) than those who were infected with HCV-1b (37%), and they were also more likely to sustain that response (33% vs. 6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775959 TI - Follow-up of antibody responses to human papillomavirus type 16 E7 in patients treated for cervical carcinoma. AB - A synthetic peptide comprising amino acids 6-35 of HPV-16 E7 was used in an ELISA to screen sera taken from 31 cervical carcinoma patients. Sera obtained before and during treatment, and in follow-up, were tested for the presence of antibodies to this peptide. Sixteen patients with negative pretreatment serum determination remained negative during treatment and follow-up. Of the 15 patients with positive pretreatment sera, 12 showed a decrease in anti-E7 6-35 antibody level during treatment. During follow-up an increase in anti-E7/6-35 antibody level was observed in 6 out of 7 patients with progressive or recurrent disease, whereas all patients who remained in complete remission showed stable or further decreasing antibody levels. During the course of disease of the 15 seropositive patients, serum anti-E7/6-35 antibody levels were compared with serum squamous cell carcinoma antigen (SCC-Ag) profiles, a clinically useful tumor marker in the management of cervical cancer patients. Similar patterns were observed in 10 out of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7775958 TI - Hepatitis B vaccination in infants of mothers infected with human immunodeficiency virus. AB - A study was conducted to investigate the immunogenicity of a recombinant DNA hepatitis B vaccine in neonates and children of HIV-infected women. Immunization against hepatitis B consisted of three 10 micrograms doses of the vaccine administered on a 0-, 1- and 6-month schedule. The children were followed up for an average of 11 months. Of the 118 HIV-positive neonates who participated in the study, 95 lost their HIV antibodies during the follow-up period. Most (94.2%) of the latter who completed the study responded to the vaccine. Of the 23 who remained HIV-positive, 17 completed the study and 7 produced hepatitis B antibodies. PMID- 7775961 TI - Evaluation of the polymerase chain reaction for the detection of human papillomavirus from urine. AB - The ability to detect the presence of human papillomavirus (HPV)-DNA sequences in urine was evaluated using polymerase chain reaction (PCR). DNA was purified and extracted from urine samples, and subjected to 40 cycles of amplification using the consensus primer pair MY11 and MY09. Coamplification using the beta-globin primers, GH20 and PC04, was performed as an internal reaction control. Following assay optimization, urine samples from 22 women undergoing examination for cervical dysplasia were tested for the presence of HPV-DNA. PCR assay results were correlated with cytologic and histologic findings as well as ViraType assay results. Overall, HPV was detected by PCR in 16 (76%) of the interpretable samples. HPV sequences were detected in 13 (87%) of the 15 specimens from women showing evidence of condylomata, dysplasia, or invasive carcinoma. HPV was detected in 3 (50%) of the women whose cytologic or histologic results were either negative or showed benign atypia. Although the sample size in this study is small, our results show that HPV can be detected by PCR in a majority of individuals showing evidence of HPV infection. The method described provides a means for the clinical laboratory to detect a broad range of HPV types from using a sample obtained by noninvasive techniques. The ability to easily obtain urine would allow for increased numbers of individuals to be tested, and thus, aid in our understanding of HPV. PMID- 7775962 TI - Activity-Dependent Forms of Plasticity. Proceedings of a symposium. Paris, France, 1-3 February 1994. PMID- 7775963 TI - Activity-dependent forms of plasticity. PMID- 7775964 TI - The role of receptor/channel activity in neuronal cell migration. AB - Confocal laser microscopy, in conjunction with carbocyanine dyes and calcium sensitive fluorescent indicators, was used in slices and explant cultures of developing cerebellum to study cellular mechanisms underlying a motility of neuronal cell migration. The results indicate that a combination of voltage- and ligand-activated ion channels cooperatively regulates Ca2+ influx into the migrating cells. We suggest that molecules, present in the local cellular milieu, affect cell motility by activating specific ion channels and second messengers that influence polymerization of stiff and contractile cytoskeletal proteins. This early interaction between postmitotic neurons and surrounding cells controls the rate of their movements, sculpts their shapes, establishes their positions, and, therefore, indirectly determines their identities to prior formation of synaptic connections. PMID- 7775965 TI - Spontaneous calcium transients regulate neuronal plasticity in developing neurons. AB - Calcium ions play critical roles in neuronal differentiation. We have recorded transient, repeated elevations of calcium in embryonic Xenopus spinal neurons over periods of 1 h in vitro and in vivo, confocally imaging fluo 3-loaded cells at 5 s intervals. Calcium spikes and calcium waves are found both in neurons in culture and in the intact spinal cord. Spikes rise rapidly to approximately 400% of baseline fluorescence and have a double exponential decay, whereas waves rise slowly to approximately 200% of baseline fluorescence and decay slowly as well. Imaging of fura 2-loaded neurons indicates that intracellular calcium increases from 50 to 500 nM during spikes. Both spikes and waves are abolished by removal of extracellular calcium. Developmentally, the incidence and frequency of spikes decrease, whereas the incidence and frequency of waves are constant. Spikes are generated by spontaneous calcium-dependent action potentials and also utilize intracellular calcium stores. Waves are produced by a mechanism that does not involve classic voltage-dependent calcium channels. Spikes are required for expression of the transmitter GABA and for potassium channel modulation. Waves in growth cones are likely to regulate neurite extension. The results demonstrate the roles of a novel signaling system in regulating neuronal plasticity, that operates on a time scale 10(4) times slower than that of action potentials. PMID- 7775967 TI - Postnatal maturation of gamma-aminobutyric acidA and B-mediated inhibition in the CA3 hippocampal region of the rat. AB - In the adult central nervous system, GABAergic synaptic inhibition is known to play a crucial role in preventing the spread of excitatory glutamatergic activity. This inhibition is achieved by a membrane hyperpolarization through the activation of postsynaptic gamma-aminobutyric acidA (GABAA) and GABAB receptors. In addition, GABA also depress transmitter release acting through presynaptic GABAB receptors. Despite the wealth of data regarding the role of GABA in regulating the degree of synchronous activity in the adult, little is known about GABA transmission during early stages of development. In the following we report that GABA mediates most of the excitatory drive at early stages of development in the hippocampal CA3 region. Activation of GABAA receptors induces a depolarization and excitation of immature CA3 pyramidal neurons and increases intracellular Ca2+ ([Ca2+]i)] during the first postnatal week of life. During the same developmental period, the postsynaptic GABAB-mediated inhibition is poorly developed. In contrast, the presynaptic GABAB-mediated inhibition is well developed at birth and plays a crucial role in modulating the postsynaptic activity by depressing transmitter release at early postnatal stages. We have also shown that GABA plays a trophic role in the neuritic outgrowth of cultured hippocampal neurons. PMID- 7775966 TI - The Ca2+ influx induced by beta-amyloid peptide 25-35 in cultured hippocampal neurons results from network excitation. AB - Although a neurotoxic role has been postulated for the beta-amyloid protein (beta AP), which accumulates in brain tissues in Alzheimer's disease, a precise mechanism underlying this toxicity has not been identified. The peptide fragment consisting of amino acid residues 25 through 35 (beta AP25-35), in particular, has been reported to be toxic in cultured neurons. We report that beta AP25-35, applied to rat hippocampal neurons in culture, caused reversible and repeatable increases in the intracellular Ca2+ concentration ([Ca2+]i), as measured by fura 2 fluorimetry. Furthermore, beta AP25-35 induced bursts of excitatory potentials and action potential firing in individual neurons studied with whole cell current clamp recordings. The beta AP25-35-induced [Ca2+]i elevations and electrical activity were enhanced by removal of extracellular Mg2+, and they could be blocked by tetrodotoxin, by non-N-methyl-D-aspartate (NMDA) and NMDA glutamate receptor antagonists, and by the L-type Ca2+ channel antagonist nimodipine. Similar responses of bursts of action potentials and [Ca2+]i increases were evoked by beta AP1-40. Responses to beta AP25-35 were not prevented by pretreatment with pertussis toxin. Excitatory responses and [Ca2+]i elevations were not observed in cerebellar neuron cultures in which inhibitory synapses predominate. Although the effects of beta AP25-35 depended on the activation of glutamatergic synapses, there was no enhancement of kainate- or NMDA-induced currents by beta AP25-35 in voltage-clamp studies. We conclude that beta AP25-35 enhances excitatory activity in glutamatergic synaptic networks, causing excitatory potentials and Ca2+ influx. This property may explain the toxicity of beta AP25-35. PMID- 7775968 TI - Lamina-specific synaptic connections of hippocampal neurons in vitro. AB - By using slice cultures as a model, we demonstrate here that different target selectivities exist among the various afferent fibers to the hippocampus. As in intact animals, septohippocampal cholinergic fibers, provided by a slice culture of septum, innervate a co-cultured slice of hippocampus diffusely, that is, without forming distinct layers of termination. As in vivo, the septal cholinergic fibers establish synapses with a variety of target cells. Conversely, fibers from an entorhinal slice co-cultured to a hippocampal slice display their normal laminar specificity. They preferentially terminate in the outer molecular layer of the fascia dentata, thereby selectively contacting peripheral dendrites of the granule cells. This preferential termination on peripheral dendritic segments is remarkable, since these fibers do not have to compete with commissural fibers, hypothalamic fibers, and septal afferents for dendritic space under these culture conditions. Moreover, in triplet cultures in which first two hippocampal slices were co-cultured and then, with a delay of 5 days, an entorhinal slice was added, the fibers from the entorhinal slice and those from the hippocampal culture terminated in their appropriate layers in the hippocampal target culture. However, in this approach the normal sequence of ingrowth of these two afferents was reversed. In normal ontogenetic development, entorhinal afferents arrive in the hippocampus before the commissural fibers. The results show that there are different degrees of target selectivity of hippocampal afferents and that the characteristic lamination of certain afferent fibers in the hippocampus is not determined by their sequential ingrowth during development. PMID- 7775969 TI - Multiple forms of long-term potentiation and multiple regulatory sites of N methyl-D-aspartate receptors: role of the redox site. AB - Long-term potentiation (LTP) is a form of synaptic plasticity thought to be involved in learning and memory. Although extensively studied, mainly in the CA1 region of the hippocampus, the mechanisms underlying the induction and expression of LTP are poorly elucidated. This is probably due to the fact that LTP is not a unique process and indeed recent studies have shown that several forms of LTP could be generated depending on the experimental conditions. Furthermore, LTP is generally associated with a long-lasting increase of the synaptic efficacy of AMPA receptors but an increasing number of data also suggested that NMDA receptors could be potentiated as well. NMDA receptor responses are modulated by a large number of extracellular and intracellular events, providing additional possibilities for the generation of LTP. The role of these different modulatory sites of the NMDA receptor and their relation with LTP are reviewed with a particular attention to the redox site which seems to be a selective target to distinguish between AMPA and NMDA-LTP. PMID- 7775970 TI - Posttetanic potentiation and presynaptically induced long-term potentiation at the mossy fiber synapse in rat hippocampus. AB - A form of long-term potentiation (LTP) is induced at the mossy fiber (MF) synapse in the hippocampus by high-frequency presynaptic stimulation (HFS). It is generally accepted that induction of this form of LTP (MF LTP) does not depend on postsynaptic Ca2+ current gated by N-methyl-D-aspartate receptors, but it has remained controversial whether induction depends on postsynaptic depolarization and voltage-gated entry of Ca2+. There are also contradictory data on the time course of both LTP and post-tetanic potentiation (PTP), a shorter duration form of potentiation observed at MF synapses immediately following HFS. It has been proposed that some of these differences in results may have arisen because of difficulties in isolating monosynaptic responses to MF input. In the present study, whole cell recording was used to observe excitatory postsynaptic currents (EPSCs) elicited in CA3 pyramidal cells by input from MFs. Postsynaptic cells were dialyzed with 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and F- to inhibit postsynaptic mechanisms that required Ca2+, cells were under voltage clamp during HFS, and conditions were selected to minimize the likelihood of polysynaptic contamination. Under these conditions, HFS nevertheless induced robust LTP (mean magnitude, 62%). The possibility that EPSCs were contaminated by polysynaptic components was investigated by exposing the slices to a suppressing medium (one that partially blocked neurotransmission). EPSC waveforms did not change shape during suppression, indicating that contamination was absent. The LTP observed always was accompanied by prominent PTP that lasted through the first 5 to 15 min following HFS (mean decay time constant, 3.2 min). Induction of this LTP was not cooperative; there was no relationship between the size of responses and the magnitude of the LTP induced. LTP magnitude also was unrelated to the extent to which postsynaptic cells depolarized during HFS. These results show that high rates of presynaptic MF activity elicit robust LTP whether or not there is accompanying postsynaptic depolarization or increase in the concentration of postsynaptic Ca2+. High frequency MF activity also results in a PTP that is unusually large and long. PMID- 7775971 TI - Fast and slow excitation of inhibitory cells in the CA3 region of the hippocampus. AB - Pyramidal cells form excitatory synaptic connections with local inhibitory neurons in the hippocampus. This recurrent synapse plays a crucial stabilizing role in the control of hippocampal activity, since it transforms pyramidal cell activity into inhibition of the same pyramidal cell population. Using a combination of dual recording from presynaptic and postsynaptic cells and anatomical techniques, we show that these synaptic connections often comprise a single site for liberation of excitatory transmitter. The resulting excitatory postsynaptic potentials (EPSCs) have a fast time course and a similar amplitude to miniature EPSCs recorded in tetrodotoxin and cobalt. In contrast, activation of metabotropic glutamate receptors (mGluRs) by transmitter liberated during repetitive activation of these synapses produces an excitation with a much slower time course. In addition to somatodendritic mGluRs, which excite inhibitory cells, a different species of mGluR is present on inhibitory cell terminals. This mGluR is activated by higher concentrations of the agonist t-1-amino-cyclopentyl 1,3-decarboxylate and acts to reduce gamma-aminobutyric acid release. mGluRs, thus, have a dual action to enhance and to depress synaptic inhibition in the hippocampus. PMID- 7775972 TI - Possible strategies for finding the substrate for learning-induced changes in the hippocampal cortex. AB - For long-lasting memory traces, structural synaptic changes remain a probable mechanism. However, in higher animals it has proved difficult to provide positive evidence for this notion. The main reason may be that the changes are subtle and are to be found in a relatively small subset of synapses and in a distributed manner in the cellular network in question. Here, we discuss possible strategies for finding structural changes in the hippocampus associated with spatial learning, an activity for which this structure is important. Spatial learning may induce new excitatory synapses in a small subset of hippocampal CA1 neurons because we observe a higher spine density without alteration in dendritic length or branching. The dendritic synapses are regularly spaced, irrespective of spine density, suggesting the operation of an intersynaptic dispersing force. PMID- 7775973 TI - Fos: an immediate-early transcription factor in neurons. AB - In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c-fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus-transcription coupling. The c-fos gene can be viewed as an archetype of the set of cellular immediate-early genes encoding transcription factors. These genes are believed to function in coupling short term signals elicited by extracellular to long-term changes in cellular phenotype by orchestrating alterations in target gene expression. Several animal seizure models have been used to demonstrate the activation of gene expression in specific populations of neurons. Using a transgenic mouse approach, based on a foslacZ fusion gene, we now demonstrate an association between c-fos expression and cell death in the nervous system. A delayed and protracted induction was observed following surgical lesion and in response to neurotoxin exposure. This system allows us to determine, for the first time, the DNA regulatory sequences that are responsible for the induction of gene expression in neurons in vivo. Furthermore, foslacZ transgenic mice provide a unique resource for identifying cell populations that respond to specific stimuli or that are susceptible to particular toxins. PMID- 7775974 TI - Cell death, gliosis, and synaptic remodeling in the hippocampus of epileptic rats. AB - Seizures set in motion complex molecular and morphological changes in vulnerable structures, such as the hippocampal complex. A number of these changes are responsible for neuronal death of CA3 and hilar cells, which involves necrotic and apoptotic mechanisms. In surviving dentate granule cells seizures induce an increased expression of tubulin subunits and microtubule-associated proteins, suggesting that an overproduction of tubulin polymers would lead to a remodeling of mossy fibers (the axons of granule cells). In fact, these fibers sprout in the dentate gyrus to innervate granule cell dendrites, creating recurrent excitatory circuits. In contrast, terminal mossy fibers do not sprout in the CA3 field. Navigation of mossy fiber's growth cones may be facilitated by astrocytes, which would exert differential effects by producing and excreting cell adhesion and substrate molecules. In the light of the results discussed here, we suggest that in adult brain activated-resident astrocytes (nonproliferating, tenascin negative, neuronal cell-adhesion molecule-positive astrocytes) could contribute to the process of axonal outgrowth and synaptogenesis in the dentate gyrus, while proliferating astrocytes, tenascin-positive, could impede any axonal rearrangement in CA3. PMID- 7775975 TI - Molecular correlates between reactive and developmental plasticity in the rat hippocampus. AB - Area CA3 of the hippocampus is the most epileptogenic structure of the brain. Various studies have shown that kainate-induced experimental epilepsy in rats and human cases of epilepsy are associated with sprouting of the mossy fibers of the dentate granule neurons and selective loss of pyramidal neurons, notably in the CA3-CA4 areas of Ammon's horn. In experimental models of epilepsy, brief seizure activity initiates a cascade of molecular alterations that will contribute to changes in the expression of numerous genes, which can last several weeks. The products of some of these genes will contribute to the permanent state of enhanced synaptic efficiency, to the sprouting and formation of novel excitatory synapses, and possibly to neuronal cell loss. The expression of genes encoding transcription factors and numerous growth factors is rapidly altered following seizure episodes. Based on observations in vivo and in vitro in cultured hippocampal neurons, it is hypothesized that an interplay between transcription and growth factors, because of their pleiotropic effects on the regulation of effector genes, may be instrumental in coupling transient extracellular stimuli to irreversible cellular alterations. PMID- 7775977 TI - mRNA distribution within dendrites: relationship to afferent innervation. AB - The majority of neuronal mRNAs are confined to cell bodies, but a few mRNAs are present at high levels in dendrites. Here we report an initial analysis of the relationship between afferent innervation and the distribution of mRNA within dendritic fields. In situ hybridization techniques were used to compare the subcellular distribution of dendritic mRNAs in principal neurons of the hippocampal formation in vivo. The mRNA encoding the alpha subunit of calcium/calmodulin dependent protein kinase II (CAMII kinase) was present at high levels throughout the layers that contain the dendrites of hippocampal pyramidal cells and dentate granule cells. In contrast, the mRNA encoding the high molecular weight microtubule-associated protein MAP2 had a more limited distribution. In the dentate gyrus, labeling for MAP2 was present in a discrete band in the lamina containing proximal dendrites and decreased to low levels in laminae containing distal dendrites. This laminar pattern resembles the distinct terminations of the commissural/associational projection (high MAP2 labeling) and the entorhinal projection (lower MAP2 labeling) upon dendrites of granule cells. To determine if the differential distribution of dendritic mRNAs was regulated by either the presence or activity of afferents, we evaluated mRNA distribution in the dentate molecular layer following (1) removal of the entorhinal input by lesions of the entorhinal cortex or (2) prolonged delivery of potentiating stimulation to entorhinal afferents. Denervation led to modest decreases in the levels of mRNAs for both CAMII and MAP2 but did not lead to detectable alterations in mRNA distribution. Also, prolonged stimulation did not lead to detectable alterations in MAP2 or CAMII mRNA distribution although such stimulation clearly elevated the expression of mRNA for glial fibrillary acidic protein (GFAP). PMID- 7775978 TI - Cu(II) binding by angiotensin II fragments: Asp-Arg-Val-Tyr-Ile-His and Arg-Val Tyr-Ile-His. Competition between amino group and imidazole nitrogens in anchoring of metal ions. AB - Potentiometric and spectroscopic (absorption, circular dichroism and electron paramagnetic resonance) study on the coordination of two angiotensin II fragments (Asp-Arg-Val-Tyr-Ile-His and Arg-Val-Tyr-Ile-His) to Cu(II) ions has shown that competition between amino and imidazole nitrogens to anchor metal ions is a complicated process and may lead to formation of macrochelate rings. The important factor that influences this competition is the distance between competing His and N-terminal residues (number of spacer residues in a peptide sequence). PMID- 7775976 TI - The neural cell adhesion molecule and synaptic plasticity. AB - Highly stereotyped patterns of neuronal connections are laid down during the development of the nervous system via a range of activity independent and activity dependent mechanisms. Whereas the coarse hard-wiring of the nervous system appears to rely on molecular recognition events between the neuron, its pathway, and its target, the establishment of precisely patterned functional circuits is thought to be driven by neuronal activity. In this review we discuss the role that the neuronal cell adhesion molecule (NCAM) plays in morphological plasticity. Recent studies on NCAM and its probable species homologue in Aplysia (apCAM) suggests that an individual CAM can function to both promote synaptic plasticity and maintain the structure of the synapse. In the adult brain, changes between stability and plasticity are likely to underlie dynamic morphological changes in synaptic structures associated with learning and memory. In this review we use NCAM as an example to illustrate mechanisms that can change the function of an individual CAM from a molecule that promotes plasticity to one that does not. We also discuss evidence that NCAM promotes plasticity by activating a conventional signal transduction cascade, rather than by modulating adhesion per se. Finally, we consider the evidence that supports a role for NCAM in learning and memory. PMID- 7775979 TI - Photoaquation of cis-dichlorobis-(1,10-phenanthroline)chromium(III) and the photochemical and thermal reactions of this complex with native calf-thymus DNA. AB - The photoaquation of the title compound [cis-Cr(phen)2CL+2] has been studied using high performance liquid chromatography. Both monoaquo [cis Cr(phen)2Cl(OH2)2+2] and diaquo [cis-Cr(phen)2(OH2)3+2] products are formed, and the quantum efficiency for the loss of starting material in Tris buffer (pH 7) under argon and oxygen is 0.010 +/- 0.001 and 0.0026 +/- 0.0002, respectively. The presence of deoxyguanosine (dG) increases the rate of loss, as much as twofold under argon, but only the rate of diaquo product formation is enhanced by the nucleoside. The dG effect is attributed to reductive quenching of the cis Cr(phen)2Cl+2 excited state by the base. Equilibrium dialysis studies indicate that both cis-Cr(phen)2Cl+2 and cis-Cr(phen)2(OH2)3+2 minimally associate with calf-thymus DNA. However, photolyses of cis-Cr(phen)2Cl+2 with the nucleic acid yield a mixture of unidentified covalent adducts. The diaquo complex also forms covalent adducts with DNA in the absence of light. Photolyses of the cis Cr(phen)2Cl+2 with polyribonucleotides indicate a clear preference for covalent binding to the purines. PMID- 7775981 TI - Comparison of polysaccharide iron complexes used as iron supplements. AB - An oral hematinic marketed as "water soluble polysaccharide iron complex" (Vitaline Formulas) has been characterized using x-ray powder diffraction and Mossbauer spectroscopy. Another polysaccharide iron complex marketed as Niferex (Central Pharmaceuticals) has been previously studied by us and found to have a core similar to ferrihydrite, but with some long-range order of the mineral akaganeite, beta-FeOOH. The latter is seen in other ferric carbohydrate complexes synthesized by the hydrolysis of FeCl3. This commercial product, however, is very different and has a mixture of iron components including hematite (alpha-Fe2O3) magnetite (Fe3O4), goethite (alpha-FeOOH), iron metal, and a ferrous salt. PMID- 7775980 TI - Cobalt(III)-ligated peptides as acyl acceptors in peptide synthesis catalyzed by chymotrypsin. AB - The efficiency of cobalt(III)-ligated peptides as acceptor nucleophiles in acyl transfer reactions catalyzed by alpha-chymotrypsin was examined. A series of metallopeptides with the general formula [H-(Gly)n-OCo(NH3)5]2+ (1 < or = n < or = 4) was tested. The aminolysis rate of acyl-chymotrypsin was measured spectrophotometrically by monitoring the concentration of unreacted nucleophile. The rate of the competing hydrolysis of acyl-chymotrypsin was obtained by automatic titration with base, using a pH-stat. The main result was that the positively charged metallopeptides, in general, were more efficient nucleophiles than the corresponding amides and free peptides that were examined for comparison. A binding model that rationalizes the findings is given. PMID- 7775982 TI - Preferential interactions in the H2O/lysozyme/AlCl3 system. AB - The preferential interactions of lysozyme with solvent components is studied in aqueous solutions of AlCl3. The interaction parameter is negative at large salt concentrations, indicating that the interaction process of both salt and protein is thermodynamically favorable. The transfer free-energy parameter and the solubility data show that aluminum chloride is a salting-in agent for lysozyme. Moreover, these preferential interactions also are correlated with both protein solubility in the solvent medium and the influence of salt on the lysozyme structure. Viscometric and refractometric studies show that lysozyme can undergo a conformational change at 1 mM of salt, and spectrophotometric studies indicate a protein activity of approximately 75% at 10 mM of salt. Therefore, neither the interaction of AlCl3 with the lysozyme nor the conformational change undergone directly affect the catalytic amino acid residues of the active site. PMID- 7775983 TI - In vitro anticomplementary activity of constituents from Morinda morindoides. AB - In a screening program for complement classical pathway modulation, an 80% MeOH extract of the leaves of Morinda morindoides showed potent dose-dependent anticomplementary activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of ten flavonoids of which two were aglycones. The compounds were tested in vitro for their putative complement inhibiting properties on the classical (CP) and the alternative (AP) pathways of the complement system. The results indicated that quercetin [1], quercetin 3-O rhamnoside (quercitrin) [5], and quercetin 3-O-rutinoside (rutin) [7] showed similar anticomplementary activities (inhibition) on the CP of complement. A mixture of two kaempferol triglycosides isolated and denoted as M(015), also had a good inhibitory effect. The effects of these compounds were dose-dependent for this pathway. On the AP of complement, quercetin [1] and M(015) had, respectively, more pronounced inhibitory and activatory effects than the other tested flavonoids, but their effects were not dose-dependent for this pathway. The other isolated flavonoids showed weak effects or were inactive for both pathways. PMID- 7775984 TI - Anti-AIDS agents, 18. Sodium and potassium salts of caffeic acid tetramers from Arnebia euchroma as anti-HIV agents. AB - Monosodium and monopotassium salts [2-4] of isomeric caffeic acid tetramers were isolated from Arnebia euchroma as anti-HIV agents. Mixtures of dipotassium and disodium salts [1] of a caffeic acid tetramer and dipotassium and potassium sodium salts [5] of a caffeic acid tetramer glucoside were also isolated from the active fraction. The structures of 1-5 were characterized by chemical and spectral evidence. Compounds 2-4 demonstrated potent anti-HIV activity with EC50 values of 2.8, 4.0, and 1.5 micrograms/ml, respectively. Treatment of 1-4 with dilute HCl yielded known caffeic acid tetramers [8 and 9], which were found to be less active, indicating the importance of the sodium and potassium salts to the enhanced anti-HIV activity. PMID- 7775985 TI - New myrsinol-related polyfunctional pentacyclic diterpene esters from roots of Euphorbia prolifera. AB - Five Euphorbia substances, SPr1-SPr5, were isolated from the roots of Euphorbia prolifera. They were found to have similar structures but were inactive in a mouse ear inflammation assay. By nmr analysis and after single-crystal X-ray crystallography the structure of SPr5 was established as a hexaester (tetraacetate-benzoate-propionate) of a hitherto unknown polyfunctional pentacyclic diterpene parent alcohol, structurally related to myrsinol. As judged from its nmr spectra, SPr4 is an analogue of SPr5, carrying an isobutyrate substituent in place of a benzoate ester functionality. SPr1-SPr3 were partially characterized by their mass spectra as esters of diterpene parent alcohols possibly related to the myrsinol structure. SPr1-SPr5 may represent one of the product lines branching off the proposed main route of biogenesis of the oligocyclic diterpenoid skin irritants and tumor promoters occurring in many, but not all, of the species in the plant families Thymelaeaceae and Euphorbiaceae. PMID- 7775986 TI - Triterpenoid saponins from Ilex paraguariensis. AB - The leaves of Ilex paraguariensis have yielded three new saponins named matesaponins 2, 3, and 4 [1-3], which have been characterized by chemical and nmr methods as ursolic acid 3-O-[beta-D-glucopyranosyl-(1-->3)-[alpha-L rhamnopyranosyl- (1-->2)]]-alpha-L-arabinopyranosyl]-(28-->1)-beta-D glucopyranosyl ester, ursolic acid 3-O-[beta-D-glucopyranosyl-(1-->3)-alpha-L arabinopyranosyl]-(28-- >1)- [beta-D-glucopyranosyl-(1-->6)-beta-D glucopyranosyl]ester, and ursolic acid 3-O-[beta-D-glucopyranosyl-(1-->3)-[alpha L- rhamnopyranosyl-(1-->2)]]-alpha-L-arabinopyranosyl]-(28-->1)-[beta -D- glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]ester, respectively. PMID- 7775987 TI - Bipolal: anti-microalgal compound isolated as a candidate for marine antifouling produced by Bipolaris sp. F5206. AB - Bipolal [1], a new compound with marine antifouling potential, was isolated from the culture broth of Bipolaris sp. The structure was determined to be an eremophilane derivative on the basis of 2D nmr spectroscopy and chemical transformations. PMID- 7775988 TI - Measuring activities in clinical trials using random work sampling: implications for cost-effectiveness analysis and measurement of the intervention. AB - Determining research-related costs from intervention-related costs is important for both clinical and health services research. Often this task involves estimating what proportion of the workday personnel spend on a variety of activities. We used a portable random reminder beeper to measure the daily work activities and contacts of study nurses within the context of a multi-site randomized trial designed to assess the effectiveness of primary care. Nurses recorded 4920 work activities over 140 consecutive workdays. Research-related activities consumed the largest proportion of the workday, 42.5% (95% CI, 38.1 46.7) followed by patient care, 28.8% (24.1-33.2), personal time 16.4% (12.0 20.7), and time spent in transit 12.5% (9.1-15.9). Because this research-related time is spent performing tasks specific to the enrollment of patients and measurement of outcome variables, we will use an adjusted annual salary for these nurses (from $56,392-$32,425) when attributing costs of the intervention in cost effectiveness analyses and for future management projections. Work sampling is a flexible, inexpensive method that was well accepted by the nurses in this study. Our results provide important insights into the costs analysis of complex interventions involving health professionals and may allow us to explore why the intervention worked or did not work at individual sites. PMID- 7775989 TI - Selecting control groups for studies of familial aggregation of disease. AB - In genetic-epidemiologic studies to determine the association between the disease status of family members, this association is measured by comparing rates of the disease in relatives of probands (index cases) with the disease, with the rates of the disease among individuals in a control group. Either of two types of control groups are generally used: (1) a control group consisting of a random sample from the population or the entire population if available or (2) a control group consisting of relatives of individuals without the disease under study. We examine the advantages and disadvantages of using these different types of control groups. We show two major results for family studies: (1) when there are no other factors associated with the disease status of an individual other than the disease status of a family member, both types of control groups will give a valid test of the null hypothesis of no familial aggregation. However, tests using a population control group will always be less efficient statistically, than those performed with a control group of relatives of probands without the disease under study, the degree of efficiency decreasing with increasing population prevalence of the disease. (2) When factors other than the disease status of a family member are also associated with the disease status of an individual, if this factor is a proband characteristic (which is not shared by relatives) population control groups cannot be adjusted to eliminate possible bias due to the potential confounding effect of this factor (unlike control groups consisting of relatives of probands without the disorder). PMID- 7775990 TI - Autoperception and satisfaction with health: two medical care markers in elderly hospitalized patients. Quality of life as an outcome estimate of clinical practice. AB - This paper reports a prospective study, carried out in elderly patients hospitalized for acute illness, designed to evaluate the effectiveness of medical treatment from the point of view of quality of life (QoL). Patient's autoperception and satisfaction with health, the most relevant subjective estimates of QoL, were assessed on admission to hospital and at check-up after discharge. A comprehensive functional evaluation of the patients was made. The results indicated an improvement in health autoperception coherent with the professional view. However, health satisfaction was not modified in any way after medical treatment. This dissonance could be explained because the predictors of satisfaction, age, sex, functional status and comorbidity, are the factors least modified by treatment. Satisfaction with ones own health could be a crucial marker of QoL especially for chronic diseases, but not appropriate for monitoring treatment effectiveness of acute illness. Health autoperception seems to be more desirable as an outcome estimate for this purpose. PMID- 7775991 TI - Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection. AB - The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients. PMID- 7775992 TI - Validation of a French-language version of the MOS 36-Item Short Form Health Survey (SF-36) in young healthy adults. AB - The MOS 36-Item Short Form Health Survey (SF-36) is designed to measure 8 dimensions of health in clinical and general population settings. The main aim of this paper was to examine the reliability and validity of this instrument in young adults. A secondary aim was to document the results of a rapid translation procedure of the instrument, to be compared later to the more thorough official French adaptation. The translated survey was answered in 1992 by 1007 residents of Geneva, Switzerland, 18-44 years old, identified from health insurance rolls (82% response rate). Completion rate for all 8 dimensions of health was 95.5%. The instrument demonstrated excellent covergent (100%) and discriminant (98%) validity against pre-set criteria. Interval scaling of responses could be verified in some, but not all, items. Cronbach alpha (reliability) coefficients ranged from 0.76 to 0.92. Factorial analysis yielded 2 principal components, corresponding to mental and physical health. Thirteen of 16 correlations between health dimensions and principal components were within a pre-established range. Validation by independent clinical variables was also, with few exceptions, consistent with theory. Thus the SF-36 retained excellent psychometric properties even when used in a generally very healthy group. The careful but rapid translation procedure used in this study may be an effective alternative to full scale cultural adaptations when resources are limited. PMID- 7775993 TI - Can drug treatment be improved by feedback on prescribing profiles combined with therapeutic recommendations? A prospective, controlled trial in general practice. AB - We have carried out a prospective, controlled trial to ascertain whether mailed feedback on general practitioners' (GPs) own prescribing combined with relevant recommendations on drug treatment, can improve the prescribing. The GPs in the Norwegian county of More and Romsdal recorded all their contacts with patients and prescriptions during two periods. After the first period the GPs in Romsdal only (intervention group) received a mailed report giving their prescribing profiles as well as treatment recommendations for insomnia and acute cystitis. The total number of contacts with patients was 68,625 in which 55,747 items were prescribed. The GPs in the intervention group changed their prescribing in accordance with the intervention: they prescribed significantly less sleeping pills for each patient, preferred short- to long-acting benzodiazepine hypnotics and tranquilizers, and they chose trimethoprim as a first line treatment for acute cystitis. We conclude that it is possible to improve the GPs' prescribing through mailed feedback. PMID- 7775995 TI - Stability of blood (pro)vitamins during four years of storage at -20 degrees C: consequences for epidemiologic research. AB - We studied the effects of frozen storage on (pro)vitamin concentrations in EDTA plasma and whole blood. Aliquots from 55 samples were analyzed before storage and after 3, 6, 12, 24, 36 and 48 months at -20 degrees C. Dramatic decreases occurred for EDTA-plasma concentrations of vitamin E between 6 and 12 months, vitamin A, total carotenoids and beta-carotene after 1 year, and whole blood niacin. A smaller decrease was observed for folic acid at 1 year of storage, but the level remained constant thereafter. The vitamins D, B6, B12 (EDTA-plasma), B1 and B2 (whole blood) showed no decline during 4 years of storage. With the exception of folic acid, the observed decreases varied considerably among subjects. Therefore using EDTA-plasma stored longer than 1 year at -20 degrees C will result in highly attenuated odds ratios when assessing the relationship between vitamin A, carotenoids, or vitamin E with a given disease. Attenuation will also occur when using niacin concentrations in whole blood stored for 4 years at -20 degrees C. PMID- 7775994 TI - Population-based registries using multidisciplinary reporters: a method for the study of pediatric neurologic disorders. AB - Few registries are available for evaluating population differences for rare, newly, or ill-defined pediatric neurologic disorders. The purpose of this article is to present standard methodologies for establishing a population-based registry and evaluating the completeness of a registry's case ascertainment. The Texas Rett Syndrome Registry (TRSR) is used as a model. The combination of health care and education resources has identified approx. 89-100% of the Rett syndrome cases in Texas. Cases reported by non-physician sources, although older on average (10.7 vs 7.7 years of age), did not differ by other demographic characteristics from those reported by physicians. Non-physician health and education professionals participated with the TRSR at a significantly higher rate than physicians, 89 and 37% (p < 0.05), respectively. Capture-recapture techniques, both two-sample and log-linear modeling, were used to quantitatively evaluate case ascertainment. Standardized national and international population-based registries could be the basis of an initiative to identify the etiology and perhaps preventive measures for pediatric neurologic disorders. PMID- 7775996 TI - Competing mortality risks and differential survival. PMID- 7775997 TI - The etymology and pathogenesis of "wonk". PMID- 7775998 TI - Vulvo-vaginal candidiasis associated with acitretin. AB - The aim of this study was to estimate the risk of vulvo-vaginal candidiasis among the users of acitretin. The incidence rate ratio of vulvo-vaginal candidiasis was estimated in a cohort of acitretin users by using prescription sequence analysis. Study subjects were 196 women between 15 and 45 years of age, exposed to acitretin in 1990. Prescriptions of drugs for treatment of vulvo-vaginal candidiasis were used as proxy for the occurrence of vulvo-vaginal candidiasis. Validation of the proxy drug was performed by record linkage of pharmacy and medical records. In addition to the risk estimation by incidence rate ratios a case-crossover study with patient-stratified logistic regression analysis was performed to control for distortion due to individual differences in contribution of exposure time. The positive predictive value of the proxy drug for vulvo vaginal candidiasis ranged between 57 and 100%, the sensitivity was 87% and the specificity estimated 99%. The crude incidence rate ratio for vulvo-vaginal candidiasis following acitretin exposure was 2.8 (CI95%: 1.1-7.1). The pooled Mantel-Haenszel incidence rate ratio was 3.3 (CI95%: 1.1-9.6) after stratification for accumulated level of exposure. Patient-stratified analysis on the subgroup of cases (n = 15) revealed an odds ratio of 6.5 (CI95%: 2.3-18.2). This study strongly suggests that the higher occurrence of vulvo-vaginal candidiasis during acitretin exposure is attributable to the drug. PMID- 7776000 TI - The use of unlicensed assistive personnel. When to support, oppose, or be neutral. PMID- 7775999 TI - The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec. AB - Despite the potential benefits of using prescription claims databases for pharmacoepidemiological research, little work has been reported on the nature of available information or its accuracy. The purpose of this study was to describe information contained within the prescription claims database in Quebec, and to assess the accuracy of drug information that might be used to monitor drug exposure and physician prescribing. The comprehensiveness of the prescriptions claims database was assessed by examining 1,917,214 records of dispensed prescriptions for a regionally stratified random sample of 65,349 Quebec elderly in 1990. We found that values in key fields (individual identifiers, drug, quantity, date dispensed and duration) were missing or out of range in 0-0.4% of records. The accuracy of data were examined in 723 prescriptions filled by 306 elderly patients attending one internal medicine clinic. Of these prescriptions, 83% were filled by the patient and correctly identified the patient and drug and in 89% of these 599 records, the prescribing physician was correctly identified. The quantity and duration of the prescriptions were accurate in 69.1% and 72.1% of records, respectively. We conclude that the prescription claims database in Quebec may represent one of the most accurate means of determining drugs dispensed to individuals. There may be limitations in using this database for dosing information. PMID- 7776001 TI - The nurse entrepreneur. Legal aspects of owning a business. AB - For those nurse executives and managers with an innovative flair and a desire for increased personal and professional autonomy and flexibility, becoming an entrepreneur holds promise of potential financial and personal rewards. The freedom associated with flexible hours and job setting enables many nurses to balance work, family, or school commitments. Along with these rewards come the legal responsibilities of owning and managing a business--something many nurse entrepreneurs believe is well worth the investment. PMID- 7776002 TI - Healthcare in transition. Labor law impact on nurse-supervisor roles. AB - The United States Supreme Court has issued a new decision concerning the representation rights of nurses who exercise supervisory authority on behalf of their employers. However, the holding of the decision may reflect a view of labor management relations that is outdated, given the massive changes that healthcare is going through in the 1990s. PMID- 7776003 TI - The impact of a wireless telecommunication system on time efficiency. AB - With the increased acuity of patients and the resultant complexity of care required, effective and efficient communication among patients, nurses, and physicians is a critical variable in patient outcomes. In recognition of the need for rapid communication between health professionals, University Hospital in Denver, Colorado, instituted a wireless telecommunication system on two medical surgical nursing units. Evaluation research of this innovation in practice revealed a significant time savings by both nurses and clerical staff members. This time savings translates into improved patient care because skilled personnel have more time available for direct patient care. PMID- 7776004 TI - Expanding services through student placements: Strategies for the home health administrator. AB - As home healthcare becomes increasingly "high-tech," home health administrators struggle to provide nursing students with traditional community health nursing experiences. The gap between education and service widens as university faculty turn to other community health agencies, including academic nursing centers, for clinical placements. Strategies that administrators and faculty can use to modify current clinical experiences in ways that expand agency services while meeting the educational goals are presented. PMID- 7776005 TI - Home Care Steps protocols: Home care's answer to changes in reimbursement. AB - Home care agencies must plan for increasing demands from managed-care organizations; federal, state, and local governments; and consumers to provide appropriate, timely, high-quality, and cost-effective home healthcare services. Providers of home care services need a methodology to appropriately manage and control their service delivery. The Home Care Steps protocols discussed in this article provide such a methodology. PMID- 7776006 TI - The proactive management of rumor and gossip. AB - Gossip and rumor are common forms of communication in the workplace. Consequently, nursing administrators are challenged to find ways to manage these grapevine activities. The authors present an analysis of gossip and rumor and discuss strategies for their prevention and control. PMID- 7776007 TI - Pulling the plug. PMID- 7776008 TI - Supplemental staffing. Nurse manager views of costs, benefits, and quality of care. AB - The authors identified nurse managers' perceptions of supplemental staffing costs, benefits, and quality of care related to patient care delivery and knowledge of the setting. Qualitative responses related to perceptions of costs and benefits were analyzed. Perceptions of quality of care were more positive when related to actual patient care delivery, but relatively negative for items relating to knowledge of policies, procedures, and care delivery setting. PMID- 7776009 TI - Dealing with inappropriate behavior on a multidisciplinary level: A policy is formed. AB - Rapid changes due to healthcare reform have impacted the patient care setting, demanding that care is provided in an efficient manner--a team working in harmony to meet patient care needs. However, inappropriate behavior at the work site continues to rob healthcare providers of valuable time as they stop to regroup from its effects on staff and organizations. A search in the Dixie Regional Medical Center in St. George, Utah, to solve this age-old dilemma led to the formation of a policy to guide staff members in a positive direction when resolving conflict issues. This article addresses these efforts. PMID- 7776010 TI - Nurses' retirement preparation. AB - Nurses expect that professional achievement and dedication to society will reward them with economic security in their later years. Such rewards may not be theirs without deliberate and careful attention to early preparation. This study showed that although nurses expect an adequate income during retirement, their current pension, benefit, and savings status suggests otherwise. Nurses who do not actively manage personal finances or attend to details of employment benefit packages place themselves at distinct risk for economic crisis during their decades of retirement. PMID- 7776011 TI - Identifying the best in nurse executive leadership: Part 1, Questionnaire results. AB - Further analysis of a previously reported transformational leadership study indicated that the study's 81 excellent nurse executives can be further delineated into four groups based on the difference between the scores of nurse executives and staff for transformational and transactional leadership. Part 1 reports questionnaire results, indicating that staff identify two groups as more highly transformational. Part 2 will identify further characteristics of these groups based on interview data results. PMID- 7776012 TI - One fellow's perspective. Reflections on the J & J Wharton Fellows Program for nurse executives. PMID- 7776013 TI - Primary care for women. Comprehensive sexual health assessment. AB - This article discusses the fundamentals of sexual functioning and describes the elements of a comprehensive, developmentally relevant sexual health assessment. Personal barriers that may prevent clinicians from comfortably addressing sexual issues are discussed, and useful strategies for facilitating effective, reciprocal communication during a sexual health history are presented. A therapeutic intervention model for counseling, referral, and sexual health assessment of women in the primary care setting is also included. PMID- 7776014 TI - Primary care for women. Assessment of hematologic disorders. AB - This article reviews hematopoiesis, the pathophysiology of selected hematological disorders, and the components of the health history and physical exam that are needed to make a complete assessment of women with a variety of hematological disorders. The laboratory testing and interpretation of tests that augment the assessment of women with signs and symptoms of hematological disorders are also included. PMID- 7776015 TI - Primary care for women. Comprehensive cardiovascular assessment. AB - This article identifies the tools necessary for basic primary care assessment and evaluation of the cardiovascular system in women. Risk factors and abnormalities associated with cardiovascular problems are discussed. Guidelines are presented that will enable the primary care clinician to determine normal cardiovascular function in women, identify risk factors that indicate the need for preventive care, and discover abnormalities that may require referral and intervention. PMID- 7776016 TI - Primary care for women. Comprehensive assessment of the respiratory system. AB - This article reviews the anatomy and physiology of the respiratory system and provides techniques for the physical assessment and data collection for common respiratory complaints in women. The pertinent historical, physical examination, and laboratory data for asthma, pneumonia, bronchitis, cough, and tuberculosis are also presented. This article is the first of two articles on primary care for women with respiratory complaints; the subsequent article will address primary care management of common respiratory conditions. PMID- 7776017 TI - Primary care for women. Comprehensive assessment of the neurologic system. AB - This article reviews the essential neuroanatomy and neurophysiology, and summarizes the components of the health history, physical exam, and laboratory tests required for an assessment of the neurologic system within the primary care setting. Brief case studies illustrate the wide range of symptoms associated with neurologic disorders in women and the manner in which the pattern of symptoms can be used to locate the site of pathology and indicate the need for referral and follow-up. PMID- 7776018 TI - Primary care for women. Comprehensive dermatologic assessment. AB - This article identifies the components necessary for comprehensive dermatologic assessment, including the pertinent anatomy and physiology, appropriate health history, and physical examination strategies. An overview of common dermatologic conditions in women is presented, and the identification of and action needed for life-threatening dermatologic conditions are reviewed. This article is the first of two articles on primary care for women with dermatological complaints; the subsequent article will address primary care management of common dermatologic conditions. PMID- 7776019 TI - Primary care for women. Comprehensive assessment of the head and neck. AB - This article reviews the pertinent anatomy of each body system involved in the assessment of the head and neck (including the eyes, ears, nose, and throat) and describes the basic elements of the comprehensive health assessment. Frequently encountered chief complaints are discussed. Aspects of the health assessment that will assist the primary care provider in making a differential diagnosis and determining the need for referral are presented. This article is the first of two articles on this topic; the subsequent article will address primary care management of common conditions of the head and neck. PMID- 7776020 TI - Primary care for women. Comprehensive assessment of common musculoskeletal disorders. AB - This article reviews the common musculoskeletal disorders that are likely to be encountered in the women's primary care setting. Basic anatomy and physiology of the musculoskeletal system are reviewed, and the assessment and treatment of complaints of strains, sprains, low back pain, chest pain, carpal tunnel syndrome, musculoskeletal pain syndrome, fibromyalgia, osteoporosis, and osteoarthritis are discussed. Examples of low-technology treatment strategies are included. PMID- 7776021 TI - Primary care for women. Comprehensive assessment of gastrointestinal disorders. AB - This article summarizes the anatomy and physiology of the gastrointestinal system, reviews physiologic changes that occur with normal development, and discusses considerations for the primary care provider in gathering health history information and conducting the physical exam. The use of diagnostic testing during the evaluation of women with gastrointestinal complaints is reviewed. A case study is used to illustrate an integrated approach to diagnosis and management of gastrointestinal disorders of women in the primary care setting. PMID- 7776023 TI - Primary care for women. The nurse-midwifery legacy. PMID- 7776022 TI - Primary care for women. Assessment and management of genitourinary tract disorders. AB - This article reviews the basic anatomy and physiology of the genitourinary system and disorders commonly encountered in the primary care setting. The role of the nurse-midwife in the assessment and treatment or referral of complaints of dysuria, hematuria, and incontinence is discussed. The treatment of nonpregnant women with cystitis is addressed; symptoms associated with pelvic relaxation are discussed, and a management scheme for teaching effective pelvic floor exercises is presented. PMID- 7776024 TI - Primary care for women. An overview of the role of the nurse-midwife. AB - The nurse-midwife's past, present, and future roles in the primary care of women are explored using a recent Institute of Medicine report on primary care as a framework for discussion. Primary care, the scope of services, and the role of the primary care clinician are described, and specific strategies for a primary care emphasis in basic nurse-midwifery education are addressed. The nurse midwife's future roles in collaborative practice for the primary care of women and the need for continuing education opportunities in primary care are also discussed. PMID- 7776026 TI - Primary care for women. Environmental assessment of the home, community, and workplace. AB - This article presents the primary health care provider with an overview of basic environmental health issues, discusses symptoms related to environmental exposures, and provides a review of the steps involved in comprehensive environmental assessment. Guidelines for assessing women within the context of the home, community, and workplace are provided. PMID- 7776027 TI - Primary care for women. The art of interviewing. AB - This article focuses on the skills, attitudes, and goals required for effective history-taking during comprehensive health assessment in the primary care setting. The approach presented is characterized as "patient-centered" in that the woman is engaged in the problem-solving process. Specific communication skills are discussed, and attitudes and goals that enable primary care providers to adopt a patient-centered approach to relationship-centered care are included. PMID- 7776025 TI - Primary care for women. Screening tests and preventive services recommendations. AB - This article reviews public health prevention principles and screening test requirements and discusses current guidelines that underlie widely used preventive services recommendations. The reasons and rationales that govern the screening of healthy asymptomatic women for certain diseases are reviewed. This update will prepare nurse-midwives for enhanced roles in health promotion, an important aspect of the scope of primary care services for women. PMID- 7776028 TI - Internal fixation of calcaneus fractures: an anatomical study of structures at risk. AB - This study examines the risk of injury to medial soft-tissue structures during the fixation of calcaneal fractures performed through a lateral approach. An L shaped lateral incision was performed on 10 fresh cadaver feet. The calcaneus was divided into three zones for study. Ten K-wires were inserted in a standard configuration from a lateral starting point extending through the medial cortex. The feet were dissected medially to measure the distance from each exiting K-wire to the medial and lateral plantar vessels, the calcaneal branch of the posterior tibial nerve, and the tendons of the flexor hallucis longus, flexor digitorum longus, and posterior tibialis. The mean risk of injury to these medial structures was calculated for each lateral insertion site. Wires placed in the subchondral bone of the posterior facet or anterior to the critical angle of Gissane were determined to be at high risk of injury to the medial soft tissues. Structures at risk included the medial and lateral plantar nerves and vessels and the flexor hallucis longus tendon. Caution should be exercised when inserting K wires, drills, and screws into high-risk areas to avoid iatrogenic injury to the medial structures. PMID- 7776029 TI - Hematoma block for ankle fractures: a safe and efficacious technique for manipulations. AB - The purpose of this study was to examine the safety and efficacy of the hematoma block technique for closed ankle fracture manipulation. Twenty-three patients received a hematoma block with or without supplemental analgesia and/or sedation for the manipulative reduction of an ankle fracture, and 37 patients received parenteral agents alone. At an average of 12 months post-reduction, patients were administered a questionnaire concerning their level of discomfort surrounding the manipulation of their acute injury. Their experienced level of pain was recorded on a pain analog scale at the time of injury, at the time of reduction, and at the time of the questionnaire. Other queries were made regarding their recall of other aspects of their acute care treatment. The hematoma block group noted their pain differential to be 3.4 less during reduction compared with the time of injury. In the 17% subgroup of hematoma block patients who received no supplemental parenteral analgesia, the pain differential was noted to be 4.5 less during reduction. This was in contrast to the non-hematoma block group, which rated their pain differential to be 0.6 between injury and reduction. In addition, the hematoma block procedure resulted in no associated complications. The results of this study led us to conclude that the hematoma block with or without supplemental analgesia for the manipulation of ankle fractures was safe and effective and is a useful technique. This is particularly true in those patients in whom an adequate dosage of parenteral medication is contraindicated or unsafe. PMID- 7776030 TI - Management protocol for unreamed interlocking tibial nails for open tibial fractures. AB - Over a 15-month period, 41 open grade I-IIIA tibia fractures were treated with unreamed interlocking nails. A protocol previously established by the authors to enhance fracture union was followed. The purpose of the study was to determine if union rate for the comminuted statically locked fracture could be reduced through early dynamization, bone grafting, or a combination of both. Of the 41 patients, 15 had grade I wounds, 12 had grade II wounds, and 14 had grade IIIA wounds. Fracture classification using the Orthopaedic Trauma Association Classification showed 19 42A fractures, 15 42B fractures, and seven 42C fractures. Fifteen of the 41 fractures required dynamization for rotational and axial stabilization. Of these 15 patients, five subsequently underwent dynamization only, six underwent autogenous bone grafting, and three underwent both dynamization and bone grafting, one of which also underwent exchange rodding. One patient underwent bone grafting and exchange rodding. Comparing the fractures of these 15 patients to similar fractures previously reported, union rate was reduced from 37 to 24 weeks. This was statistically significant to 0.002. It is the authors' recommendation that statically locked unreamed tibial nails be dynamized and/or bone grafted at 6-8 weeks postinjury to enhance union and reduce the time of fracture healing. PMID- 7776031 TI - Osteomyelitis in grade II and III open tibia fractures with late debridement. AB - The purpose of this study was to compare the incidence of infection in grade II and III open tibia fractures with respect to early and late debridement. All grade II and III tibia fractures treated between January 1988 and January 1992 were reviewed. Forty-seven fractures (25 grade II and 22 grade III) in 46 patients were eligible for entry into the study. In all grade II and III fractures, one of 15 fractures (7%) debrided in < or = 5 h became infected. Twelve of 32 fractures (38%) debrided > 5 h after injury became infected (p < 0.03). Overt manifestations of infection did not appear until an average of 4.8 months from the time of injury, and the infecting organisms correlated with the initial cultures in only 25% of the cases. Negative postdebridement cultures did not preclude subsequent infection. The Injury Severity Score did not appear to correlate with increased risk of subsequent osteomyelitis. PMID- 7776033 TI - Open dislocation of the knee. AB - Traumatic open dislocation of the knee is an infrequent, severe injury associated with extensive ligamentous damage and a high incidence of vascular and neurologic involvement. Eighteen patients with 19 open knee dislocations were treated at the affiliated hospitals of the University of Pennsylvania and Louisiana State University Medical Center during an 18-year period. Final results included three above-knee amputations, one knee fusion, and one total knee arthroplasty. The 14 knees salvaged had only fair to poor function according to the Hospital for Special Surgery Knee Injury Score at an average follow-up of 36 months after the injury (average score = 29, range - 17 to 37). Nine patients (47%) had concomitant neurologic or vascular injury, and eight patients (42%) had wound healing difficulties. Five complete disruptions of the popliteal artery or posterior tibial artery underwent emergent revascularization, successful in three of the extremities, with the remaining two extremities requiring above-knee amputations. These massive injuries are often limb-threatening despite prompt surgical intervention and early antibiotic therapy. There is a very high incidence of infection and neurologic injury with a guarded prognosis for limb survival and satisfactory function. PMID- 7776032 TI - Intramedullary nailing of aseptic tibial nonunions without the use of the fracture table. AB - Twenty-seven patients with 28 aseptic nonunions were treated with reamed intramedullary (IM) nailing of the tibia and were followed for at least 1 year postoperatively. The management protocol called for a radiolucent operating room table with the limb draped free and manual manipulation of the nonunion with a preference for closed nailing. Nail interlocking was used when residual axial or rotational instability was observed after nail insertion. Iliac crest bone grafting was performed on all patients requiring open nailing. Closed nailing, using the described technique, was accomplished in 20 cases; open nailing was necessary in eight. Although operative time and total blood loss were significantly increased with open nailing, time to union was similar in the two groups. Twenty-seven nonunions healed. The lone persistent nonunion responded to bone grafting, leaving the nail in situ. One infection occurred, which responded to debridement, drainage, and long-term antibiotic therapy without requiring nail removal. Acceptable bony alignment was attained in all patients. Functional results were excellent. This method is recommended for all tibial nonunions amenable to IM nail stabilization. A history of prior acute infection and/or excessive shortening due to bone loss constitute the relative contraindications. PMID- 7776034 TI - Response of the lateral meniscus of the dog to wide incision and repair of the meniscotibial ligament. AB - The effects of extensive incision and reattachment of the coronary ligaments on meniscal healing in the canine were examined. Through an extensile exposure to the lateral tibial plateau, nine mongrel dogs underwent wide incision, reflection, and subsequent reattachment of their meniscotibial ligaments. At intervals of 3, 6, and 9 weeks, three dogs were killed and a gross and microscopic evaluation of their menisci and perimeniscal tissues was performed. At 3 weeks, a small region of the central meniscal periphery was found to be devoid of a vascular network. By 6 weeks, the entire peripheral vasculature had reconstituted. No specimen demonstrated histologic evidence of meniscal necrosis or degeneration. Healing occurred by fibrovascular scar. PMID- 7776035 TI - Distal femur as a donor site of autogenous cancellous bone graft. AB - We performed a prospective clinical study and a cadaveric study to evaluate the morbidity associated with harvesting cancellous bone from the distal femoral metaphysis for use in the lower extremity. Thirty patients underwent harvest of distal femoral cancellous bone: 13 for acute trauma and 17 for reconstructive procedures. The distal femoral condyle is approached through a 6-cm midlateral, longitudinal incision. A small cortical window is created, bone graft is harvested, and the cortical window is replaced. All patients were kept nonweight bearing on the extremity for a minimum of 6 weeks. Patients were followed for an average of 10 months (range 3-32 months) and no patient was lost to follow-up before allowing full weight bearing. There were no donor site would or neurovascular problems and no femur fractures. A cadaveric study was also performed in which bone was harvested from the distal femur, the bone was quantified, and the knees were tested in compression (axial loading). The bone harvested knees failed in the same load range as the contralateral control knees did. The distal femoral metaphysis has many advantages compared with the iliac crest in cases when cancellous bone is needed for the lower extremity. Harvesting distal femoral bone is associated with little morbidity if performed correctly, and if the patient remains nonweight bearing for 6 weeks. PMID- 7776036 TI - Mechanics of retrograde nail versus plate fixation for supracondylar femur fractures. AB - Two common types of internal fixations for the supracondylar femur fractures--the retrograde intramedullary nail and the 95 degrees sideplate and screw--were mechanically tested in synthetic composite femur bones to determine the quantitative differences in their inherent rigidity. The medial and lateral femoral condyles were separated by a sagittal osteotomy, and a standardized medial segmental shaft defect was created at the distal shaft. The osteotomized specimens were stabilized using one of the two implants and were tested in different modes of loading. The bending stiffness of both constructs were not significantly different in varus compression, medial bending (pure varus), and bending in flexion. The plate and screw implant was three times stiffer in lateral bending (pure valgus) and 1.2 times stiffer in valgus compression than the retrograde supracondylar nail (p < 0.01). The torsional stiffness of the plate and screw implant was significantly higher, 1.6 times that of the nail. Clinically, the most important and common cause of implant failure is varus loadings due to loss of medial cortical contact. Although the retrograde nail was less rigid in other physiologically less critical modes of loading, it had a rigidity comparable to that of the plate in varus loading. Therefore, a supracondylar nail may be considered a mechanically possible alternative to plate fixation. PMID- 7776037 TI - Sural nerve grafting for lower extremity nerve injuries. AB - Fourteen consecutive patients who had sural nerve grafts to reconstruct the sciatic or peroneal nerve were retrospectively evaluated to determine the functional return of reinnervation. A standardized functional evaluation to assess motor and sensory return of the injured compared with the contralateral side was employed as a means of normalizing the data. The dorsiflexion and plantar flexion strength were quantitatively measured to determine the recovery of muscle strength, and recorded as a percentage of the strength of the contralateral extremity as well as by assigning a motor grade. Sensory recovery was evaluated by sensory grade, two-point discrimination, and response to Semmes Weinstein monofilaments. The average age of these 14 patients was 20 years (range 8-63 years). All but one of the patients regained protective sensation and five patients regained useful motor function. Four of the five patients regaining useful function were pediatric patients. Improved functional outcome was correlated to the nerve injured, patient age, mechanism of injury, length of graft, and the delay to grafting. The return of lower extremity function, obviating the need for bracing, can occur in children but is a rare occurrence in the adult patient although protective sensation is routinely gained and disabling paresthesias from neuromas are avoided. PMID- 7776038 TI - Effects of supine positioning and fracture post placement on the perineal countertraction force in awake volunteers. AB - An instrumented traction post was used to determine the magnitude and direction of the countertraction force applied to the perineum of 15 awake volunteers for a series of 12 positions used in fracture surgery and compared with their corresponding neutral position controls. The results demonstrated that adduction of the affected limb and abduction of the contralateral limb applied the greatest force to the perineum with ipsilateral and contralateral placement of the fracture post. These two maneuvers increased the perineal countertraction force 80% above their respective neutral readings. Abduction of the affected limb reduced the traction force by 50% with ipsilateral and contralateral placement of the fracture post. Flexion-abduction-external rotation of the contralateral leg reduced the forces applied to the perineum by 60% when the fracture post was placed contralateral to the affected limb. Contralateral placement of the post decreased the perineal countertraction force 46% below the value for ipsilateral post placement for this maneuver. Internal and external rotation of the affected limb had no effect on the perineal countertraction force for either placement of the post. There was a significant decrease in the perineal forces for the neutral positions after adduction of the affected limb and abduction of the contralateral limb with ipsilateral placement of the post, indicating that the volunteers shifted on the fracture table in response to pain. There was no significant difference in the direction of the countertraction force for the various positions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776039 TI - Treatment of fracture blisters: a prospective study of 53 cases. AB - From June 1987 to January 1993, 53 fractures complicated by overlying blisters were identified and prospectively followed. Data concerning the mechanism of injury, time course in the development of the fracture blisters, clinical characteristics of the blister, fracture type and management, and soft-tissue treatment and outcome were collected. Clinically, two types of blisters were identified: clear fluid filled and blood filled. Methods used to treat the skin blister were: aspiration of the blister, deroofing of the blister with subsequent application of Silvadene cream or coverage with a nonadherent dressing, and leaving the blister intact and covered by a loose gauze or exposed to the air. No significant difference was found in the outcome of the skin injury treated with the various modalities. Nineteen patients underwent early open reduction and internal fixation in the presence of intact fracture blisters. In 17 cases the incision healed within 3 days, sealing off the deeper structures, and reepithelialization of the blister bed then occurred at a later date. Two of the patients who had incisions pass through blood-filled blisters developed wound healing complications. Although there was no significant difference in the outcome of the soft-tissue treatment techniques, our present practice is to leave all fracture blisters intact. If the blisters rupture spontaneously, they are deroofed and covered with a nonadherent dressing. Early surgery is contemplated in patients with intact blisters and without severe swelling. PMID- 7776040 TI - Marginal mandibular nerve palsy due to compression by a cervical hard collar. AB - A case history of a trauma patient who developed a palsy of the marginal mandibular nerve from compression by a cervical spine hard collar is presented. After clinical and radiographic screening found no evidence of occult cervical spine pathology, the collar was removed; the palsy resolved uneventfully during the next 2 days. PMID- 7776042 TI - The unstable shoulder girdle: early functional treatment utilizing open reduction and internal fixation. AB - The unstable shoulder girdle--a combination of a scapular neck fracture with a clavicular fracture, acromioclavicular dislocation, or sternoclavicular dislocation--represents a rare and often underestimated injury. Sufficient treatment to permit early function is necessary to avoid a frozen shoulder as well as to treat concomitant thoracic injuries. This is possible only by open reduction and internal fixation. In most cases this can be achieved by a sole osteosynthesis of the clavicular injury. We retrospectively analyzed 12 cases and classified the results according to the Constant Score. This analysis showed excellent functional results in nearly all cases. PMID- 7776043 TI - The use of sonography for evaluation of the integrity and healing process of the tibiofibular interosseous membrane in ankle fractures. AB - This study evaluates the value of sonography in the diagnosis of the rupture and healing process of the interosseous membrane in Weber type B and C ankle fractures. In 90 such fractures a rupture of the interosseous membrane was intraoperatively observed in 35 cases (38.8%). All Weber type C fractures showed a rupture of the interosseous membrane, whereas only 23% of the Weber type B fractures were associated with a rupture of the interosseous membrane (p < 0.001). In the vast majority of the cases (77%), particularly in all Weber type B fractures (p < 0.01), the rupture of the interosseous membrane extended above the proximal fracture line of the fibula. By means of sonography, in the acute posttrauma period a rupture of the interosseous membrane was found in 37.4% of the cases. Thus, in our series the results of sonography and the operative findings coincided in 88.6% of the cases concerning location, type, and extent. Sonography was performed by three unbiased observers, and the results were compared with the intraoperative findings. Thus, the sensitivity of the sonography in the diagnosis of the rupture of the interosseous membrane was 88.8%, the diagnostic value of the method 92.2%, and specificity 94.5%. The sonographic findings of the healing process of the interosseous membrane were in absolute (100%) agreement with the intraoperative observations at the time of removal of the osteosynthesis material. Complete healing occurred within 3-5 months after trauma in 70% of the cases of ruptured interosseous membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776044 TI - Profiting from managed care. PMID- 7776041 TI - Traumatic dislocation of the lateral sesamoid of the great toe: nonoperative management. AB - A case of traumatic dislocation of the lateral sesamoid of flexor hallucis brevis tendon associated with metatarsal neck fractures due to a crush injury is reported. This patient was treated nonoperatively by elevation, application of plaster, and then free mobilisation. The patient has now fully recovered and remains completely asymptomatic despite residual sesamoid dislocation 1 year after the injury. The nonoperative management of this injury has not, to our knowledge, been reported previously. PMID- 7776045 TI - Evaluation of osseointegration of endosseous implants in radiated, vascularized fibula flaps to the mandible: a pilot study. AB - PURPOSE: This study clinically evaluated the osseointegration of implants placed into vascularized fibula flaps used in mandibular reconstruction of cancer patients following radiation treatment and subsequent hyperbaric oxygen (HBO) therapy. MATERIALS AND METHODS: Five head and neck cancer patients had mandibular resection and immediate reconstruction with a vascularized fibula flap. Subsequent therapy included greater than 50 Gy of radiation to the fibula flap over a 6 to 8-week period. Two to 6 weeks following radiation therapy each patient received 20 90-minute daily sessions of HBO at 2.4 atmosphere pressure. Stage 1 implant surgery was performed placing two to six implants (15 mm in length and 3.75 to 4.0 mm in width) into each fibula flap. This was followed by 10 postoperative HBO sessions using the previously mentioned protocol. The stage 2 procedure was performed 6 months after the stage 1 procedure. Osseointegration was assessed clinically using manual force and an electronic device at the time the implants were uncovered and monthly over a 6-month period. RESULTS: All 20 implants placed in the fibula flaps were osseointegrated clinically at the time the implants were uncovered and during the 6-month follow-up. CONCLUSION: In this pilot study, mandibular reconstruction with a vascularized fibula flap and endosseous osseointegrated implants, following radiation of the fibula, was successful. It was concluded that factors such as the graft having its own blood supply and the use of HBO contributed to the successful osseointegration of these implants. PMID- 7776046 TI - Are mandibular third molars a risk factor for angle fractures? A retrospective cohort study. AB - PURPOSE: Anecodotal reports suggest that the presence of mandibular third molars predispose the mandible to angle fractures. The purpose of this study was to evaluate mandibular third molars as risk factors for angle fractures in a patient sample with fractured mandibles. MATERIALS AND METHODS: The medical records and panoramic radiographs of a patient cohort with mandible fractures was retrospectively reviewed. Data were collected for the following variables: age, sex, race, mechanism of injury, number and location of mandible fractures, and the presence and position of the mandibular third molars. RESULTS: Of the 73 patients with mandibular third molars, 30 (41.1%) had angle fractures. Of the 28 patients without mandibular third molars, 3 (10.7%) had angle fractures (P = .004). CONCLUSION: The results of this study demonstrate that patients with fractured mandibles and mandibular third molars are 3.8 times more likely to have an angle fracture than patients without mandibular third molars. PMID- 7776047 TI - An evaluation of velopharyngeal ring ligation in cleft palate repair. AB - PURPOSE: This article describes the details of the velopharyngeal ring ligation procedure (VPRL) and compares the results with those achieved with the von Langenbeck (VL) and pharyngeal flap procedures (PFP). PATIENTS AND METHODS: A random sample of 52 patients was evaluated postoperatively by phonation tests, measurement of oral pressure, pharyngeal fluoroscopy, and cineradiography. RESULTS: The results showed that the speech of the VPRL group was significantly better than that of the VL group. The velopharyngeal competence rate, the anteroposterior nasopharyngeal minimal diameter, the left-right nasopharyngeal minimal diameter (both in repose and on phonation), and the length of the soft palate were significantly different between VPRL and VL, and between VPRL and PFP. Differences in the velar angle were significant between VPRL and PFP and between PFP and VL, but there was no significant difference between VPRL and VL. CONCLUSIONS: VPRL is a better method for cleft palate repair than the VL or PFP procedures. It can reduce the nasopharyngeal space circumferentially, thus improving the patient's speech. PMID- 7776048 TI - Maxillary sinus aspergillosis: diagnosis and differentiation of the pathogenesis based on computed tomography densitometry of sinus concretions. AB - PURPOSE: The efficacy of preoperative computed tomography (CT) densitometry in evaluating the origin of sinus concretions (SC) in sinus aspergillosis (SA) and its value for differentiation between a dental (endodontic) and an aerogenic pathogenesis were examined. PATIENTS AND METHODS: Thirty-two patients who demonstrated radiodense maxillary sinus concretions in standard radiography underwent an additional preoperative CT examination of the maxillary sinus and the SC. The density of the SC and the root canal filling materials was assessed. The SC were subdivided into organic (< 1,500 HU) and inorganic (> 1,500 HU) masses; this classification was useful in the differentiation between a dental and an aerogenic pathogenesis of SA. RESULTS: SA was diagnosed in 22 patients (68.8%). The SC of SA patients had a density of 2,566.5 +/- 713.6 HU, whereas those of patients without SA had a density of 1,159.9 +/- 1,008.4 HU (P < .01). A correlation between the density of inorganic SC and that of root filling materials was found (r = .78, P < .01). CONCLUSION: CT densitometry allows a classification of SC into two subgroups. The correlation between the density of root filling materials and that of radiodense sinus concretions seems to point to a "dental" origin of some concretions in SA. However, "organic" masses found in CT densitomentric examinations represent endogenous fungal products, which indicate an aerogenic pathogenesis of SA. Additional CT examinations of radiodense sinus concretions may thus be of some value for diagnosing SA and differentiating their pathogenesis. PMID- 7776049 TI - Use of TiNiCo shape-memory clamps in the surgical treatment of mandibular fractures. AB - PURPOSE: This study tested the clinical application of shape-memory clamps for fixation of mandibular fractures using transoral access. MATERIALS AND METHODS: Clamps made of Ti50Ni48.7Co1.3 alloy were used to fix mandible fractures. These clamps automatically recovered their programmed shape at body temperature. The clamps were used to treat all types of fractures occurring between the mandibular angles. Postoperative maxillomandibular fixation was not required. Clamps were removed after a period of at least 6 weeks, and tissue samples were taken for microscopic examination. RESULTS: Seventy-seven patients with mandibular fractures were treated using the shape-memory clamps. There were 19 women and 58 men, from 17 to 74 years old. Altogether 93 fractures were treated, involving 124 clamps. There were 56 cases of single fractures and 21 cases of multiple fractures. In 72 patients the treatment progressed satisfactorily; in five cases infections occurred. Histologic examination of tissue taken from 58 patients after removal of the clamps did not indicate any atypical tissue reactions or signs of disturbed cell maturation. CONCLUSIONS: The application of shape-memory clamps for surgical treatment of mandible fractures facilitates treatment while ensuring stable fixation of the bone fragments. No pathologic tissue reactions to the implants were observed in either animals or humans. PMID- 7776051 TI - Intraoral defect coverage with muscle flaps. AB - PURPOSE: This study investigated whether wound healing after the use of purely muscular flaps for intraoral defect coverage is negatively influenced by insipient muscular atrophy and the absence of a covering layer. MATERIALS AND METHODS: In an experimental study, microsurgical transplantation of muscle flaps from the anterior abdominal wall was carried out in 18 Lewis rats. A nerve anastomosis for motor reinnervation was not performed. Atrophy of the muscle flaps was determined by measuring the reduction of their size and weight after 3, 8, and 20 weeks. In the clinical part of the study, free muscle transplants from different donor regions (vastus lateralis, pectoralis major, internal oblique, and temporalis muscles) were used for defect coverage in various areas of the oral cavity. To study epithelization, punch biopsy specimens from the muscle surface were taken at periods of 2 to 4 weeks up to 6 months for histologic evaluation. Final evaluation of reconstruction results with special regard to speech, tongue mobility, mouth opening, chewing, and swallowing took place after 6 months. RESULTS: In the experimental study, average weight loss of the muscle flaps was 67% after 20 weeks, and the remaining surface area was 71%. The number of myocytes was only about 30% compared with control muscles, and parts of the flap appeared as a thin fibrous membrane. Clinically, this atrophy led to restricted mobility in such areas as the floor of the mouth, the buccal plane, and the tongue. Muscle flaps covering solid structures such as bones or reconstruction plates adapted well to the transplant bed, and the atrophy of the muscle led to no constriction of the surrounding tissue. Atrophy also did not have a negative effect when muscle flaps were placed in the region of the pharyngeal wall. Epithelization started from the edges after 2 weeks and was concluded after 8 weeks in all transplants if no additional radiation was performed. The muscle tissue was sufficiently resistant so that infection, fistulization, and necrosis did not occur. CONCLUSIONS: Muscle flaps undergo considerable atrophy with a cicatricial transformation and reduction of flexibility. Despite these disadvantages they can be used in the hard palate, the alveolar crest, and in the pharyngeal wall without causing functional restriction. Because of constriction of the surrounding tissues, mobile areas such as the buccal plane, the floor of the mouth, and the tongue are not suitable as sites for muscle transplants. PMID- 7776050 TI - The effects of orthodontic treatment on isometric bite forces and mandibular motion in patients before orthognathic surgery. AB - PURPOSE: Little is known about the effects of orthodontic treatment on oral motor function. The objective of this report is to evaluate changes in mandibular motion and maximum bite force that occur between the initiation of presurgical orthodontics and its completion before surgery. PATIENTS AND METHODS: Fifteen patients (9 women, 6 men) with a variety of dentofacial deformities were examined before and after presurgical orthodontics. Mechanical advantage of the muscles and bite points, mandibular range of motion, maximum isometric bite force, and levels of electromyographic (EMG) activity in the anterior and posterior temporalis and masseter muscles during isometric bites were recorded on all subjects over time. Data obtained before and after completion of presurgical orthodontics were statistically compared. RESULTS: Presurgical orthodontics reduced mandibular mobility somewhat, but the amount was not significant. Statistically significant reductions in bite force were noted after orthodontics for incisor, canine, premolar, and molar bite positions. No significant difference in the EMG/bite force slopes was obtained, nor was there any difference in the moment arms of the bite points or the muscles of mastication from orthodontics. CONCLUSIONS: This study showed significant changes in measures of oral motor function resulting from orthodontic treatment. A larger study is needed to confirm that these results will be similar in all orthodontic patients. There is no indication that these changes are the result of physiologic alterations of the muscles of mastication. The best current explanation is that these changes result from the pain and discomfort of the orthodontic appliances and the induced malocclusion. PMID- 7776053 TI - Bilateral pseudogout of the temporomandibular joint: report of case and review of literature. PMID- 7776052 TI - Early carcinoma of the oral cavity: a conservative approach with radiation therapy. PMID- 7776054 TI - Giant peripheral ossifying fibroma of the maxilla: report of a case. PMID- 7776056 TI - Actinomycosis presenting as a midline palatal defect. PMID- 7776055 TI - Leiomyosarcoma of the tongue: a case report. PMID- 7776057 TI - Mandibular hemangiopericytoma: report of a case and review of the literature. PMID- 7776058 TI - Multiple granular cell tumors of the oral cavity: report of a case and review of the literature. PMID- 7776059 TI - Singultus: a distressing postsurgical complication. PMID- 7776060 TI - Adenomatoid odontogenic tumor: report of an unusually large lesion in the mandible. PMID- 7776061 TI - Use of pharyngoplasty to improve resonance in adult closed-head injury patients: report of cases. PMID- 7776062 TI - Severe cutaneous foreign body giant cell reaction after temporomandibular joint reconstruction with Proplast-Teflon. PMID- 7776063 TI - The use of an orthodontic appliance to stabilize a temporomandibular joint- continuous passive motion machine. PMID- 7776064 TI - Avoiding problems when switching an endotracheal tube. PMID- 7776065 TI - Untoward events associated with use of midterm i.v. devices. AB - The placement of a peripheral i.v. device causes increased stress for many individuals, sometimes causing temporary and self-limiting responses, described as vasovagal reactions. Report monitoring has identified adverse experiences that exceed anticipated reactions to stress and that may be life threatening. Untoward events have been reported during or immediately after insertion of midterm peripheral i.v. devices made of an elastomer/hydrogel polymer. Although the cause of these reactions remains unclear, it is a reminder that to identify and evaluate device-related issues, untoward events must be assessed, treated, evaluated, documented, and reported. PMID- 7776066 TI - Polyurethane and silicone: myths and misconceptions. AB - Silicone elastomer has been the standard by which other catheter materials have been judged. In the past ten years, technical advances in polymer research have provided the medical manufacturer with a wide variety of new materials for catheter manufacture. Thermoplastic polyurethane has shown great promise as an alternative to silicone for vascular catheters. This article examines the basic properties of the two materials and describes the findings in the literature that show comparable biocompatibility properties for both materials. PMID- 7776067 TI - Pulsatile i.v. insulin therapy for severely out of control diabetes. AB - A recently published National Institutes of Health study shows that tight blood glucose control is critical to averting diabetic complications. However, a small fraction of patients with diabetes cannot safely achieve tight blood glucose control even under the regimen employed in the study. Pulsatile i.v. insulin therapy (PIVIT) can help these severely ill patients gain control of their diabetes. After more than a decade of research, PIVIT is now in routine clinical use for severely out of control diabetes. PIVIT is performed on an outpatient basis at a number of hospitals and clinics around the United States. The clinical availability of PIVIT for severely out of control diabetes offers an important alternative for the approximately 1% of patients who are unable to attain the benefits of tight control through conventional means. PMID- 7776068 TI - The role of the i.v. specialist in health care reform. AB - IV nurses must have a better understanding of health care reform to understand why hospitals are decreasing nursing positions in general and why administrators always seem to cut i.v. nursing positions first. It is also important to learn strategies that i.v. teams can adopt to demonstrate their contribution to quality patient care so they are less likely to be eliminated. PMID- 7776069 TI - Abnormal tympanography after supine bottle feeding. AB - OBJECTIVE: To determine whether bottle feeding with the infant in the supine position is related to entry of milk into the middle ear, thereby predisposing the infant to otitis media. STUDY DESIGN: Ninety children, aged 7 to 24 months, who were free of respiratory infection and had normal tympanograms initially, were bottle fed in either the supine or the semiupright position, and tympanography was repeated immediately afterward. RESULTS: Thirty-four (59.6%) of the 57 infants fed in the supine position had abnormal postfeeding tympanographic results compared with only five (15%) of the 33 infants fed in the semiupright position (p < 0.005). In addition, when the infants with abnormal tympanograms were placed in semiupright or prone positions for 15 minutes after feeding, the majority of tympanograms returned to normal. CONCLUSION: These data suggest that supine bottle feeding has a significant effect on middle-ear pressure dynamics, probably caused by the aspiration of milk into the ear. The results also suggest that repositioning infants after feeding may mitigate the effects of supine feeding, at least in healthy children. Although this study did not demonstrate that tympanographic abnormality definitely predisposes to otitis media, it provides more evidence to encourage the practice of feeding infants in a semiupright position. PMID- 7776070 TI - The clinician's role in teaching proper infant feeding techniques. AB - The species-specific advantages and significant nutritional and health benefits of breast-feeding are widely acknowledged. Less recognized are the advantages of the process of breast-feeding itself. Adherence to the natural mechanics of breast-feeding will preclude many of the problems associated with improper bottle feeding. For example, the semiupright position of the infant during breast feeding helps eliminate the entry of milk into the middle ear and reduces choking and regurgitation. The action of suckling during breast-feeding minimizes the intake of air. In addition, the direct eye contact that is natural to breast feeding fosters bonding, and the close body contact promotes a sense of security in the child. These advantages, so natural to breast-feeding, are likely to be absent from bottle feeding unless some of the natural techniques associated with breast-feeding are adopted. This article describes various aspects of the breast feeding process with the goal of urging practitioners to instruct patients to transfer these techniques to bottle feeding. In so doing, clinicians may help their patients avoid the hazards of improper bottle feeding. PMID- 7776071 TI - Quantitative and qualitative video analysis of infants feeding: angled- and straight-bottle feeding systems. AB - OBJECTIVE: To determine whether an angled-bottle feeding system is more effective than a straight-bottle feeding system in facilitating the medically recommended semiupright infant posture and to determine whether an angled bottle promotes improved ergonomic alignment and comfort for the feeder. STUDY DESIGN: On two consecutive days, 23 pairs of parent-infant teams, seated in an ergonomic chair, were videotaped at the same time of day, during which infants were fed by their parents with either an angled or a straight bottle (presented in balanced order) fitted with the infants' regular nipple. Infants were given their regular type and amount of formula. RESULTS: The angled bottle provided a higher level of satisfaction compared with the straight bottle. Less gastric discomfort occurred with the angled bottle versus the straight bottle when each was compared with the bottle used at home. In addition, feeders assumed ergonomically sound positions. CONCLUSION: This study indicates that an angled bottle is preferable to a straight bottle because it encourages more physiologic positioning of the infant, improves the comfort level of the feeder, improves ergonomic feeding performance, and decreases the need for burping. PMID- 7776072 TI - Nipple confusion: toward a formal definition. AB - The purposes of this article are to introduce a formal definition of nipple confusion and to propose various hypotheses concerning its cause. The term nipple confusion refers to an infant's difficulty in achieving the correct oral configuration, latching technique, and suckling pattern necessary for successful breast-feeding after bottle feeding or other exposure to an artificial nipple. Many early breast-feeding failures are attributed to nipple confusion, although scientific data are lacking to document its prevalence, the mechanisms involved, or various factors that predispose an infant to this phenomenon. Two classifications of nipple confusion are recommended to distinguish the impact of artificial nipples during the newborn period from their influence after breast feeding is well established. Maternal and infant risk factors making an infant more susceptible to nipple confusion are discussed. Future studies are planned to help elucidate the nature of nipple confusion and identify the circumstances under which infants are most vulnerable to this phenomenon. Meanwhile, it would seem prudent for clinicians to identify newborns at risk for nipple confusion and to minimize the use of bottle feedings in such babies. Medically indicated supplements in the early days of life could be provided by alternative methods, such as cup, spoon, or dropper feeding, until breast-feeding can be established. PMID- 7776073 TI - Imaging evaluation of breast-feeding and bottle-feeding systems. AB - OBJECTIVE: To compare infant sucking and swallowing patterns during feeding with a new artificial nipple and during breast-feeding. METHODS: Fifteen healthy, term infants were fed successfully for 1 week with use of the new tricut nipple; then each infant's oral cavity was examined during feeding by using real-time ultrasonography. Measurements of nipple length and compression were made, together with observations concerning the integrity of the seal formed by the infant's mouth around the nipple. These data were compared with similar data from previous studies of 16 breast-fed infants. RESULTS: Although no artificial feeding system exactly simulates breast-feeding, the new tricut nipple was sucked in a manner similar to the way the human nipple is sucked and delivered milk posteriorly to the foramen cecum region of the tongue, just as the breast does. CONCLUSION: Although further studies are necessary, to evaluate other characteristics of the new tricut nipple, the measurements from this investigation are useful additions to the ultrasound data these investigators have accumulated on various artificial feeding systems. These data may also prove helpful in determining the most appropriate nipples for infants with various feeding disorders. PMID- 7776074 TI - Comparative safety and efficacy of two immune globulin products in Kawasaki disease. AB - OBJECTIVE: To compare the safety and efficacy of various intravenously administered immune globulin (IVGG) products in patients with Kawasaki disease. METHODS: We performed a retrospective matched-pair study of 45 pairs of patients, matched by age, gender, hospital, and illness day when IVGG therapy was initiated. All patients received aspirin, 80 to 100 mg/kg per day; one of each pair received Venoglobulin, 2 gm/kg (product A), and the other received Iveegam, 2 gm/kg (product B). Safety was assessed during and after IVGG infusion by recording rigors, pruritus, hypotension, urticaria, and nausea. Treatment efficacy was evaluated by posttreatment height and duration of fever, and subsequent echocardiographic changes. RESULTS: Untoward reactions during infusions occurred more often with product A (25%) than with product B (2%) (p < 0.025); most reactions were rigors (18% vs 2%) (p < 0.05). Therapy was completed in all patients. Height of fever and proportion of patients febrile each day after product A or B did not differ significantly. No differences were found in the frequency of coronary artery abnormalities 1 year after illness. CONCLUSIONS: No significant differences in efficacy appeared between the two IVGG products, but they differed significantly in non-life-threatening adverse reactions, especially infusion-related rigors. Other IVGG products should be evaluated in a similar fashion. PMID- 7776075 TI - A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. AB - This randomized, double-blind trial compared the efficacy of nebulized epinephrine with salbutamol in the treatment of infants with acute bronchiolitis. The mean percent oxygen saturation at 60 minutes was significantly higher in the epinephrine group. Thirty-three percent of the patients in epinephrine group were admitted to the hospital compared with 81% of the salbutamol group (p = 0.003). We conclude that nebulized epinephrine is more efficacious than salbutamol for infants with acute bronchiolitis seen in an emergency department. PMID- 7776076 TI - Antibiotic-associated hemorrhagic colitis without Clostridium difficile toxin in children. AB - We describe nine children with antibiotic-associated hemorrhagic colitis without Clostridium difficile toxin. The onset was usually sudden, with severe hematochezia and abdominal cramps. The illness quickly resolved and required no specific treatment except discontinuation of the implicated antibiotic. Early proctosigmoidoscopy was a useful diagnostic adjunct. It appears that antibiotic associated hemorrhagic colitis is a distinct entity rather than a variant of antibiotic-associated colitis in children. PMID- 7776078 TI - Discordance for hyperinsulinemic hypoglycemia in monozygotic twins. PMID- 7776079 TI - Comparison of fiberoptic and conventional phototherapy for neonatal hyperbilirubinemia. PMID- 7776077 TI - Abnormalities in control of ventilation in newborn infants with myelomeningocele. AB - OBJECTIVE: The objective of this study was to assess respiratory responses of newborn infants with myelomeningocele through pneumograms and carbon dioxide challenge, and to evaluate the possibility of predicting which patients with myelomeningocele acquired respiratory symptoms related to the Arnold-Chiari deformity and brain-stem dysfunction. METHODS: All surviving infants with spina bifida who were born at the University of Iowa Hospitals and Clinics (UIHC) or were transferred there on the first day of life between January 1987 and January 1991 were assessed with a pneumogram and CO2 challenge once they were medically stable, and were followed for a mean of 30 months (10 to 53 months). RESULTS: Thirty patients met the inclusion criteria for this study; four died before being studied. Of the 26 remaining patients, 12 were born at the UIHC and 14 were transferred to the UIHC on the first day of life. Of the 26 infants studied, 12 (46%) had abnormalities on the pneumogram, including 2 with significant periodic breathing and 10 with episodes of desaturation below 87%. Of the 26 infants studied, 4 had no detectable response to an increasing fraction of CO2 in inspired air on the CO2 challenge and 12 had an increase in exhaled minute ventilation per increase in the alveolar fraction of CO2 in exhaled air more than 2 SD below the mean. Only 10 patients (38.5%) had normal ventilatory responses to the increasing fraction of CO2 in inspired air. On follow-up, only one study patient had symptoms related to Arnold-Chiari deformity and brain-stem dysfunction (bilateral vocal cord paralysis). His neonatal CO2 challenge results and his pneumogram were normal. CONCLUSION: We conclude that these two tests are not useful in predicting which patients will have symptoms related to Arnold Chiari deformity. Specificity for the pneumogram and the CO2 challenge was 0.52 and 0.36, respectively. Sensitivity was zero for both tests, although this result is limited by the low incidence of symptomatic Arnold-Chiari deformity in this sample. As previous investigators have found, a significant number of patients with meningomyelocele had abnormal ventilatory patterns. These ventilatory abnormalities indicate that even in the absence of severe symptoms, the control of the ventilatory response is somewhat impaired in many patients with meningomyelocele. This alteration in ventilatory control is probably related to abnormalities in the development of the brain stem. PMID- 7776081 TI - Hemoglobin A1c levels in young patients with diabetes beyond the "honeymoon" period. PMID- 7776080 TI - Single-day therapy for rickets. PMID- 7776082 TI - Lactic acidosis in a patient with acute lymphoblastic leukemia. PMID- 7776083 TI - True hermaphroditism with 46,XY karyotype and a point mutation in the SRY gene. PMID- 7776084 TI - Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn. AB - Successful management of severe PPHN depends on the application of appropriate strategies to manage the cardiopulmonary interactions that characterize this syndrome. Manifestations of PPHN often involve dysfunctional pulmonary vasoregulation, with suprasystemic pulmonary vascular resistance causing extrapulmonary shunting, pulmonary parenchymal disease causing intrapulmonary shunting, and systemic hemodynamic deterioration. Inhaled NO can cause marked improvement in oxygenation when optimal lung inflation is achieved and systemic blood volume and vascular resistance are adequate. Although concern has been expressed regarding potential increases in costs associated with this new therapy, we have found that the successful application of inhaled NO in PPHN has reduced costs of hospitalization and duration of hospital stay by approximately 50% and 40%, respectively. However, inhaled NO alone is unlikely to cause sustained improvement in oxygenation in neonatal hypoxemic respiratory failure associated with severe parenchymal lung disease without extrapulmonary shunting. Inhaled NO may be an important tool in the management of severe PPHN when its application is limited to patients with severe extrapulmonary shunting and vigilant attention is given to changes in the clinical course. PMID- 7776085 TI - Vertical transmission of human immunodeficiency virus type 1: autologous neutralizing antibody, virus load, and virus phenotype. AB - OBJECTIVE: To evaluate immunologic and virologic correlates of vertical transmission of human immunodeficiency virus type 1 (HIV-1). DESIGN: Case-control study. PATIENTS: Women who were prospectively enrolled in a natural history study of HIV-1 infection in women and infants. Sixteen HIV-1-infected women whose infants became infected were matched by CD4+ cell percentage and use of zidovudine during pregnancy with women whose infants did not become infected. MEASUREMENTS: Maternal autologous neutralizing antibody, virus load determined by RNA-polymerase chain reaction (RNA-PCR), and virus phenotype. RESULTS: Most women in both groups had low titers of autologous neutralizing antibody, and no difference in neutralizing titers was observed (range, < 4 to 181 in both groups). The HIV-1 copy number in maternal plasma was not significantly different in the two groups but was inversely correlated with maternal CD4+ cell percentage (p < 0.005). Five women in the transmitting group and four in the non transmitting group had syncytium-inducing (SI) phenotype virus. Two infected infants had SI phenotype virus. The SI phenotype virus was associated with a greater HIV-1 copy number in maternal plasma (p < 0.05) and an increase in the mortality rate for the infants (p < 0.01). CONCLUSIONS: In women matched for CD4+ cell percentage, low titers of autologous neutralizing antibody, high virus load, and SI phenotype virus were not associated with an increased risk of transmission of HIV-1 to their infants. PMID- 7776086 TI - Cytokine elevations in infants with bacterial and aseptic meningitis. AB - We sought to determine whether the detection of cytokines, produced during the inflammatory response, would aid in the diagnosis of meningitis in young infants. We measured cerebrospinal fluid (CSF) and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) in 62 infants less than 6 months of age whose condition was evaluated for meningitis. Twenty infants had culture-proved meningitis, 22 had aseptic meningitis, and 20 control infants had no evidence of meningitis. The CSF IL-6 levels were elevated in all 20 infants with bacterial meningitis and in 9 of 22 infants with aseptic meningitis but were undetectable in all control subjects. Furthermore, CSF IL-6 levels were 10 times greater in infants with bacterial versus aseptic meningitis (p < 0.001). Levels of TNF in CSF were detected in 12 of 20 infants with bacterial meningitis and were undetectable in infants with aseptic meningitis and in control infants (p < 0.02). Plasma IL-6 and TNF levels were unreliable for the detection of meningitis in this patient population. We conclude that the presence of IL-6 in the CSF reliably identifies infants with meningitis and that the presence of CSF TNF is a highly specific indicator of bacterial meningeal inflammation. PMID- 7776087 TI - Efficacy of an observation scale in detecting bacteremia in febrile children three to thirty-six months of age, treated as outpatients. Occult Bacteremia Study Group. AB - OBJECTIVE: To assess the efficacy of the Yale Observation Scale (YOS) in detecting occult bacteremia in febrile, ambulatory pediatric patients with no apparent signs or symptoms of severe infection and with no focal infection. DESIGN: YOS scores were assigned as part of a prospective, multicenter, randomized, interventional trial of oral and intramuscular antibiotics in preventing the complications of occult bacteremia in febrile children. SETTING: Pediatric emergency departments at eight urban medical centers. PARTICIPANTS: Children, 3 to 36 months of age with a temperature at least 39.0 degrees C, a nonfocal, non-toxic-appearing illness (or uncomplicated otitis media), treated as outpatients. INTERVENTIONS: None. RESULTS: There were 6611 assessable patients, who had both a blood culture result and a YOS score assigned. The median YOS score for both patients with bacteremia (n = 192) and patients without bacteremia (n = 6419) was 6, but the mean rank among patients with bacteremia was significantly higher (p < 0.0001). The sensitivity, specificity, and positive and negative predictive values for a YOS score greater than 10 were 5.2%, 96.7%, 4.5%, and 97.1%, respectively. CONCLUSIONS: The YOS scores are higher among patients with bacteremia than among patients without bacteremia, but the difference is not clinically useful in detecting occult bacteremia in febrile children, with nonfocal, apparently nontoxic infection, treated as outpatients in this age group. PMID- 7776088 TI - Clinical characteristics and risk factors for Vibrio cholerae infection in children. AB - Surveillance was conducted during February and March 1991 in the pediatric emergency department of Cayetano Heredia Hospital, Lima, Peru, to contrast the characteristics of children with epidemic cholera with those of children with noncholera-associated diarrhea. Among 626 patients 14 years of age or younger, Vibrio cholerae O1 was isolated from stool specimens of 310 patients (49%), more commonly from children older than 24 months of age (66%; p < 0.0001) than from younger children. Cholera was clinically characterized by a more sudden onset; watery diarrhea; and associated abdominal pain, muscle cramps, and vomiting, which led to more severe dehydration and hospitalization more often than in noncholera cases. Only one patient with cholera died, for a case-fatality rate of 3.2 deaths per 1000 persons. Nonpotable water and uncooked foods were identified as probable vehicles for V. cholerae. The frequency of diarrhea among relatives of patients with cholera suggested intrafamily transmission. This study of epidemic cholera describes the clinical features and the risk factors for acquisition of the infection, and points out the low case-fatality rate with prompt and appropriate treatment. PMID- 7776089 TI - A reexamination of the risk factors for the sudden infant death syndrome. AB - OBJECTIVE: To determine which risk factors are specific for the sudden infant death syndrome (SIDS) rather than characteristic of postneonatal deaths in general. STUDY POPULATION: The live births and infant death cohorts of the 1988 National Maternal and Infant Health Survey. METHODS: Information on live births, deaths from SIDS, and postneonatal deaths from other causes was abstracted from the National Maternal and Infant Health Survey. To account for oversampling of certain populations, the data were weighted to reflect national counts. Risk factors were defined as black race, birth weight less than 1500 gm, birth weight less than 2500 gm, gestational age at birth less than 37 weeks, 5-minute Apgar score less than 7, male gender, more than two previous pregnancies, maternal age less than 20 years, maternal education level less than 12 years, multiple births, and maternal smoking during pregnancy. Odds ratios (ORs) and 95% confidence intervals (Cls) were calculated to compare the SIDS with the live births cohort, infants who died of other causes with the live births cohort, and SIDS with non SIDS deaths. The population-attributable risk percentage was computed for risk factors independently associated with SIDS when compared with other postneonatal deaths. RESULTS: For all characteristics other than a 5-minute Apgar score less than 7, the ORs comparing infants who died of SIDS with the live births cohort were significantly greater than 1.0. Similarly, ORs comparing infants who died of other causes with the live births cohort were also greater than 1.0, except for male gender. When the two infant death cohorts were compared, only maternal smoking during pregnancy and low maternal education level were significantly more common among the SIDS group. After we controlled for cigarette smoking, the adjusted OR for low maternal education level was not significantly greater than 1.0. However, even after control for low maternal education level, prenatal exposure to tobacco was significantly more common among the SIDS group than in infants dying of other causes (OR = 1.97; 95% Cl, 1.59 to 2.45). On the basis of an adjusted OR of 2.92 when the SIDS group was compared with the live births cohort, the population-attributable risk percentage for maternal smoking as a risk factor for SIDS was 30%. CONCLUSION: Among characteristics generally thought to be risk factors, only maternal smoking during pregnancy was independently associated with SIDS. Data from this nationally representative sample indicate that if women refrained from smoking while pregnant, up to 30% of SIDS might be prevented. PMID- 7776090 TI - Economic comparison of a tissue adhesive and suturing in the repair of pediatric facial lacerations. AB - OBJECTIVE: To determine, from the societal perspective, the most cost efficient of the three methods commonly used to repair pediatric facial lacerations: nondissolving sutures, dissolving sutures, or a tissue adhesive (Histoacryl blue). DESIGN: Cost-minimization analysis and willingness-to-pay survey. SETTING: Tertiary-care pediatric emergency department. METHODS: All differential costs relevant to equipment utilization, pharmaceutical use, health care worker time, and parental loss of income for follow-up visits were calculated for each method. On the basis of previous research, our model assumes equal cosmetic outcome for the three methods. In addition, a convenience sample of 30 parents were surveyed in the emergency department to rank their preferences and willingness to pay for the three methods of wound closure. RESULTS: The reduction in cost (in Canadian dollars) per patient of switching from the standard nondissolving sutures was $49.60 for switching to tissue adhesive and $37.90 for dissolving sutures. Sensitivity analyses performed on key variables did not significantly alter our conclusions. Of those parents surveyed; 90% (95% confidence interval, 74% to 98%) chose tissue adhesive and 10% (95% confidence interval, 2% to 26%) chose dissolving sutures as their first choice for wound closure. Nondissolving sutures were ranked third by 29 of 30 parents. Parents were willing to pay a median (25th to 75th percentile) of $40 ($25 to $100) for tissue adhesive and $25 ($10 to $56) for dissolving sutures if only nondissolving sutures provided by the health care system (p = 0.1). CONCLUSIONS: Tissue adhesive is the preferred method of closure of pediatric facial lacerations because it results in the most efficient use of resources and is preferred by the majority of parents. PMID- 7776092 TI - Coagulation factor deficiencies during initiation of extracorporeal membrane oxygenation. AB - OBJECTIVE: We examined the hypothesis that critically ill patients receiving extracorporeal membrane oxygenation (ECMO) have reduced clotting factor levels, which may contribute to the risk of hemorrhagic complications. METHODS: Blood samples were collected from 19 patients before and 1 hour after initiation of ECMO. Heparin present in samples was removed by ECTEOLA (epichlorohydrin triethanolamine) cellulose resin adsorption, and coagulation factors were assayed by automated techniques. Factor deficiency was defined as levels at least 2 SD less than published age-adjusted reference values. RESULTS: Thirteen patients (68%) had deficiencies of two or more factors before ECMO. Despite inclusion of factor-containing blood products in the ECMO priming solution, 10 patients (53%) had deficiencies of two or more factors after initiation of ECMO. Four patients had intracranial hemorrhages and were found to be deficient in five or more factors at the time of cannulation. CONCLUSIONS: Severe coagulation factor deficiencies are often present in patients requiring ECMO, and coagulation factors provided through the circuit prime are insufficient to ensure correction of these deficiencies. Deficiency of multiple coagulation factors may contribute to the risk of intracranial hemorrhage during ECMO; the practice of excluding factor-containing solutions from the circuit prime should be examined prospectively. PMID- 7776091 TI - Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. AB - OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke. PMID- 7776093 TI - Prediction of the outcome of growth hormone therapy in children with idiopathic short stature. A multivariate discriminant analysis. AB - OBJECTIVE: To identify, with the use of pretreatment clinical data, the children with idiopathic short stature responsive to treatment with growth hormone (GH). DESIGN: Open, prospective study in a university hospital. SUBJECTS: Patients admitted to the study met the following criteria: birth weight at least 2.5 kg, no sign of dysmorphic disease, stature less than the 3rd percentile for chronologic age (CA), linear growth velocity (GV) less than the 25th percentile for bone age (BA), no sign of puberty, maximal GH response to pharmacologic stimulation greater than 10 micrograms/L, no evidence of organic disease, treatment with daily subcutaneous administration of GH at a dose of 12 to 16 IU/m2 per week. MAIN OUTCOME MEASURES: Eight pretreatment growth variables and the increase of GV after 6 months of therapy were measured. Children with a change in GV that was greater than 2.5 cm/yr after 6 months of GH therapy were considered responders to GH. RESULTS: We studied 67 patients (44 boys). Forty patients (60%) were responders. With univariate analysis the variables found to have predictive value were GV (z score for gender and CA), bone age (z score for gender and CA), and percentage of ideal body weight. These variables were employed in a multivariate discriminant analysis. Growth velocity and BA showed the best independent discriminant analysis. Growth velocity and BA showed the best independent discriminant significance in predicting responsiveness to the initial 6 months of GH therapy. The obtained equation was as follows: Score = 0.40 + 0.92X1 - 0.87X2, where X1 is the GV z value for CA and X2 is the BA z value for CA). Using this scoring system, we obtained a specificity of 96.3% and a sensitivity of 92.5% in predicting responsiveness to GH (chi-square with Yates correction, 48.2; p < 0.001). CONCLUSIONS: Discriminant analysis may permit the pretreatment prediction of responsiveness to the initial 6 months of GH therapy in short children without GH deficiency. PMID- 7776094 TI - Clinical and biochemical characterization of short-chain acyl-coenzyme A dehydrogenase deficiency. AB - OBJECTIVE: We identified two additional patients with short-chain acyl-coenzyme A (CoA), further characterized the clinical and biochemical features of this defect, and compared it with other fatty acid oxidation defects. DESIGN: We have measured the in vitro short-chain acyl-coenzyme A dehydrogenase (SCAD) activity in six affected persons with the electron-transfer flavoprotein-linked assay in the presence and absence of anti-medium-chain acyl-CoA dehydrogenase antibody. Urine organic acids, acylglycines, acylcarnitines, and radiolabeled substrate catabolism by skin fibroblasts were also examined. RESULTS: All patients had some neurologic abnormalities, including hypotonia, hypertonia, or seizures. None of the patients had episodes of hypoglycemia; in the only patient tested, fasting ketogenesis was not impaired. Four patients were initially seen in the neonatal period, two with profound metabolic acidosis and two with mild acidemia; the other two cases were recognized in infancy. Enzymatic analysis of cultured skin fibroblasts demonstrated approximately 10% activity of SCAD when compared with control fibroblasts. Gas chromatography and mass spectrometry of urine revealed that ethylmalonic acid was present in all samples but not always at elevated concentrations; methylsuccinic acid and butyrylglycine were sporadically elevated. n-Butyrylcarnitine was often found in urine and plasma. Radiolabeled substrate metabolism was reduced to 40% to 60% of control values. CONCLUSIONS: Because affected persons do not consistently excrete characteristic metabolites, the diagnosis of this enzymatic deficiency is difficult. It is necessary to collect and analyze several urine and plasma specimens when the diagnosis is being considered in patients with neurologic abnormalities suggestive of this disorder. PMID- 7776095 TI - Prolonged dysphagia caused by congenital pharyngeal dysfunction. AB - We describe two patients with severe, isolated, congenital dysphagia caused by paralysis of the pharyngeal muscles, who recovered at the ages of 40 months and 20 months, respectively. No other evidence of neurologic or muscular dysfunction was present except for a transient paralysis of the adductors of the vocal cords in one child. Radiocinematographic studies showed paralysis of the pharyngeal stage of swallowing, with minimal involvement of the oral stage. One child refused oral feeding for several months after apparent radiologic recovery. Two other patients with a similar disorder died of tracheal aspiration at the ages of 8 months and 4 months, respectively. Autopsies showed no abnormality of the central nervous system, and the cranial nerves involved in swallowing were normal. Only five other well-studied cases of this syndrome have been reported. These observations demonstrate the existence of a type of severe, idiopathic, congenital dysphagia related to paralysis of the constrictor muscles of the pharynx, with a propensity to recover after several months or years if properly managed. The cause of the disorder is obscure, but it is probably related to a dysfunction of the central nervous system. PMID- 7776096 TI - Prevention of recurrent febrile seizures. PMID- 7776097 TI - Comparison of an optical immunoassay technique with two culture methods for the detection of group A streptococci in a pediatric office. AB - For detecting group A beta-hemolytic streptococci in an office setting, an optical immunoassay method was compared with two culture methods. The sensitivity and specificity of OIA as compared with 5% sheep blood agar cultures were 91.4% and 95.6%, and as compared with a Todd-Hewitt broth method were 90.4% and 94.1%, respectively. PMID- 7776098 TI - Diagnosis of group A streptococcal pharyngitis in a private clinic: comparative evaluation of an optical immunoassay method and culture. AB - We compared the sensitivity and specificity of the Strep A Optical ImmunoAssay (OIA) method with our routine trypticase soy agar with 5% sheep blood (TSA) culture technique and with a broth-enhanced culture in the diagnosis of group A beta-hemolytic streptococcal infection. Compared with broth-enhanced culture, the Strep A OIA had a sensitivity and specificity of 94.8% and 98.8%, respectively; TSA culture had a sensitivity and specificity of 92.5% and 99.4%, respectively. The Strep A OIA, which takes 10 minutes to perform, offered sensitivity and specificity equivalent to that of TSA culture in the diagnosis of group A beta hemolytic streptococcal pharyngitis. PMID- 7776099 TI - Relationship between parental occupation and children's oropharyngeal colonization with Neisseria meningitidis. AB - We explored, during an outbreak of meningococcal disease, whether children of parents with workplace exposure to children were at increased risk of oropharyngeal colonization with Neisseria meningitidis. In comparison with children of parents without workplace exposure to children, the risk of colonization was not increased (odds ratio = 1.62; 95% confidence interval, 0.56 to 4.72). Therefore a parent's occupation does not appear to increase the risk of their children's colonization with N. meningitidis. PMID- 7776100 TI - Consumption of soft drinks with phosphoric acid as a risk factor for the development of hypocalcemia in children: a case-control study. AB - A comparison of 57 cases (in children with serum calcium concentration < 2.2 mmol/L) and 171 controls (in children with serum calcium level > or = 2.2 mmol/L) was carried out to assess whether the intake of at least 1.5 L/wk of soft drinks containing phosphoric acid is a risk factor for the development of hypocalcemia. A significant association was found: odds ratio = 5.27; 95% confidence interval, 3.17 to 8.75; p < 0.001. The hypothesis of a causal relationship between intake of phosphoric acid-containing soft drinks and hypocalcemia warrants further investigation. PMID- 7776101 TI - Cerebral artery stenoses in Williams syndrome cause strokes in childhood. AB - Extensive narrowing of lumens of many cerebral arteries caused strokes with brain damage and chronic hemipareses in two children with Williams syndrome. Increased irritability, loss of consciousness, and seizures were initial signs. Arterial stenoses are not limited to the supravalvular aorta and pulmonary arteries in patients with Williams syndrome. PMID- 7776102 TI - Ischemic stroke and intracranial multifocal cerebral arteriopathy in Williams syndrome. AB - We describe an otherwise healthy 2-year-old patient with Williams syndrome who had a stroke as a result of intracranial multivessel focal and segmental stenotic disease. The diagnosis of Williams syndrome was confirmed by elastin gene deletion testing. Combined magnetic resonance imaging and magnetic resonance angiography, and transcranial Doppler flow studies, were used in diagnosing and monitoring the course of the disease. PMID- 7776103 TI - Pancreatic glucagon levels in infants and children with hyperinsulinemia. AB - Serum concentrations of pancreatic glucagon were measured in 40 patients with hyperinsulinemic hypoglycemia. In infants with severe disease the glucagon levels were markedly elevated; lower levels were observed in children with episodic hypoglycemia. During diazoxide treatment and after pancreatectomy, the glucagon levels decreased proportionally to suppression of the insulin secretion. Thus the secretion of glucagon seems to be retained in hyperinsulinism in proportion to the insulin hypersecretion, and an increased glucagon level indicates long during and severity of hyperinsulinemic hypoglycemia. PMID- 7776104 TI - Chronic pancreatitis in a patient with cystic fibrosis and clinical pancreatic insufficiency. AB - Pancreatitis occurs in up to 15% of patients with cystic fibrosis and pancreatic sufficiency, but the possibility of its occurrence in patients with pancreatic insufficiency has not been recognized. We describe a patient with homozygous delta F508 cystic fibrosis and typical symptoms of pancreatic insufficiency (greasy, fatty stools) in whom pancreatitis developed. PMID- 7776106 TI - Bayley-Pinneau method of height prediction in girls with central precocious puberty: correlation with adult height. AB - One of the sequelae of idiopathic central precocious puberty (ICPP) can be short adult stature. In this retrospective study adult height was normal in 90% of girls with untreated ICPP (mean, 161.4 +/- 7.7 cm). The height prediction made at the time of initial examination and the height age correlated with adult height. Therefore the initial height prediction can be useful in identifying those girls with ICPP at risk for short stature. PMID- 7776105 TI - Beneficial effect of growth hormone on atherogenic risk in children with growth hormone deficiency. AB - We studied changes in the atherogenic index (total cholesterol divided by high density lipoprotein cholesterol) in 12 prepubertal boys with growth hormone (GH) deficiency during 9 months of GH treatment. High-density lipoprotein cholesterol level increased until 5 months without significant changes in total cholesterol level; thus GH therapy may be beneficial in reducing the atherogenic index in boys with GH deficiency. PMID- 7776107 TI - Acquired platelet dysfunction with eosinophilia in white children. AB - Acquired platelet dysfunction associated with eosinophilia has been described mainly in indigenous Southeast Asian and East Indian children. We describe two white boys in whom this disorder developed after they had lived in Malaysia for 12 to 18 months. Acquired platelet dysfunction associated with eosinophilia should therefore be considered in children who, after a visit to this region, have easy bruising and esoinophilia. PMID- 7776108 TI - Effect of airway pressure on inferior vena cava pressure as a measure of central venous pressure in children. AB - We evaluated the effect of elevated airway pressure on the validity of intravascular pressure obtained in the distal inferior vena cava (IVC) as a measure of central venous pressure (CVP) in a group of children receiving mechanical ventilation. The IVC pressure correlated well with CVP in the patients without abdominal distention, but the disparity was wider in those with abdominal distention. Elevated mean airway pressure or positive end-expiratory pressure had no effect on the relationship of IVC to CVP. PMID- 7776109 TI - Peutz-Jeghers syndrome in a neonate. AB - A 15-day-old girl was found to have generalized gastrointestinal polyposis resulting from Peutz-Jeghers syndrome. Her manifestations included abdominal distention, hematemesis, bloody diarrhea, and edema. She died at 1 year of age of multiple complications of her disease. PMID- 7776110 TI - Double-blind, randomized trial of one versus three prophylactic doses of synthetic surfactant in 826 neonates weighing 700 to 1100 grams: effects on mortality rate. American Exosurf Neonatal Study Groups I and IIa. AB - At 33 hospitals in the United States, a double-blind, randomized clinical trial was performed to compare one versus three prophylactic doses of synthetic surfactant in 700 to 1100 gm inborn infants. All 826 infants received an initial prophylactic dose of surfactant within 30 minutes of birth. Subsequently 410 infants received two doses of placebo (air) 12 and 24 hours later, and 416 infants received two additional doses of surfactant. By the age of 28 days, 70 infants who received one dose of surfactant and 40 infants who received three doses were dead, a 43% relative reduction in the mortality rate (30 fewer deaths; p = 0.002). By the age of 1 year after term, 87 infants who received one dose and 62 infants who received three doses were dead: a 29% relative reduction in the mortality rate (25 fewer deaths; p = 0.027). Infants who received three doses of surfactant required significantly less oxygen and less mean airway pressure for the first week of life. Necrotizing enterocolitis (9 vs 25 infants; p = 0.005), and use of high-frequency ventilation (13 vs 26 infants; p = 0.037); pancuronium (43 vs 62 infants; p = 0.045); and leukocyte transfusions (0 vs 4 infants; p = 0.042) were less frequent in the three-dose group, but air leak, bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, and infections were not different. These results indicate that physiologic findings, mortality rates, and probably morbidity rates are improved by two additional prophylactic doses of synthetic surfactant. PMID- 7776111 TI - Effects of central apnea on cerebral blood flow velocity in healthy term infants. AB - We evaluated a new method of monitoring cerebral blood flow velocity (CBFV) and described changes in CBFV in relation to central apnea in 17 healthy term infants. The area under the velocity curve during apnea did not change, whereas area under the velocity curve per the waveform showed a significant difference, suggesting that stability is maintained through an increase in CBFV with each heartbeat. The maintenance of cerebral hemodynamics during isolated central apnea supports the assumption that these episodes are benign. PMID- 7776112 TI - Soluble interleukin-2 receptor as a predictor of neonatal sepsis. AB - We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results. PMID- 7776113 TI - Reference ranges for serum cortisol and 17-hydroxyprogesterone levels in preterm infants. PMID- 7776114 TI - Conjugated hyperbilirubinemia in a newborn infant after maternal (transplacental) treatment with flecainide acetate for fetal tachycardia and fetal hydrops. AB - An infant with intrauterine supraventricular tachycardia and fetal hydrops, successfully treated with administration of flecainide acetate to the mother had conjugated hyperbilirubinemia shortly after birth. An extensive evaluation failed to disclose a known cause. We believe that in utero exposure to flecainide acetate resulted in conjugated hyperbilirubinemia in this infant. PMID- 7776115 TI - Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures. AB - Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg/kg three times a day for the first 2 days if the fever stayed greater than 38.5 degrees C, or a placebo similarly during forthcoming febrile episodes. In addition, each febrile episode was randomly assigned to be treated with acetaminophen or the placebo. Thus four groups were examined for 2 years: patients receiving two kinds of placebo, patients receiving diazepam and a placebo, patients receiving acetaminophen and a placebo, and patients receiving both diazepam and acetaminophen. Of a total of 180 patients (102 boys), 161 were followed for the 2-year period and 157 were seen at the last outpatient examination: 80 in the diazepam group and 77 in the placebo group. The final analysis of the efficacy of the drugs was made on the basis of the data from 153 patients who had had at least one febrile episode during follow-up. There were 641 fever events during this period, and 38 children (21.1%) had 55 recurrences of febrile seizures. Acetaminophen had no effect on the recurrence rate. Seizures recurred at least once in 21 patients (28.4%) receiving diazepam and 17 (21.5%) receiving a placebo (p = 0.4138, log-rank test). The combination of antipyretic agents with anticonvulsant medication did not reduce the recurrence of febrile seizures. Our results show that low doses of acetaminophen or diazepam or both are ineffective for preventing febrile seizures. PMID- 7776116 TI - Benign intracranial hypertension in children with growth hormone deficiency treated with growth hormone. AB - We report 13 cases of benign intracranial hypertension (IH) in children with growth hormone (GH) deficiency treated with GH in the United States. The group consisted of eight boys and five girls, 3 to 16 years of age (median, 9 years). The interval from starting GH therapy to diagnosis of IH was 2 weeks or less in six patients, between 2 and 12 weeks in four, 8 months in one, 5 years in one, and unknown in one. Seven patients were not known to have previously described IH risk factors; the other six had at least one factor each. All patients but one had headache, nausea, vomiting, and visual changes. All had papilledema, and cerebrospinal fluid pressures were elevated (> 250 mm H2O) in all nine patients tested. The GH dosage range was 0.17 to 0.35 mg per kilogram body weight per week (median, 0.30 mg/kg per week) for the 11 patients with dosage data. After discontinuation of GH and treatment with lumbar punctures and/or medications, signs and symptoms resolved in eight children; in two of these children signs and symptoms reappeared when GH therapy was restarted. In four patients signs and symptoms resolved while GH therapy was continued; one child was treated with a ventriculoperitoneal shunt because of an arachnoid cyst, after which GH was restarted without subsequent IH. In the 12 patients with idiopathic GH deficiency the course of IH was benign, with complete resolution of all signs and symptoms. Because doses and scheduling of GH administration have changed since the introduction of recombinant GH, higher doses and increased frequency of administration may be contributing to the development of IH in some patients. We suggest beginning therapy at the lowest recommended dose, with gradual titration to higher doses, and the performance of routine funduscopic examinations during initiation of GH therapy and whenever signs or symptoms of IH develop. PMID- 7776118 TI - Acid phosphatase in midgut digestive cells in partially fed females of the cattle tick Boophilus microplus. AB - Enzyme cytochemistry was used to identify vesicles containing acid phosphatase in the midgut digestive cells of partially fed females of the cattle tick Boophilus microplus. The vesicles were elongated or tubular in shape and appeared to be involved with the digestion of host bloodmeal. In mature cells, they were sometimes in close contact with large endosomes, which contained host blood. The vesicles were identified as tubular lysosomes because their morphological and cytochemical characteristics were analogous to similar structures described in mammalian cells. This is the first report of such lysosomes in tick gut cells and suggests some parallels with the intracellular structures involved in the digestion process of mammalian cells. Acid phosphatase in tick gut was also assayed biochemically and was shown to be inhibited with 10 mM sodium fluoride. Cytochemistry showed that this inhibitor blocked activity within the cell and on the lumenal cell membrane. PMID- 7776117 TI - Glycerophosphorylcholine, a component of both Ascaris suum muscle and Caenorhabditis elegans. AB - Studies of the muscle phospholipid metabolism of Ascaris suum suggest an effect of cholinergic drugs on the turnover of phosphatidylcholine and the generation of glycerophosphorylcholine (GPC). 31P-nuclear magnetic resonance (NMR) studies of helminths revealed the presence of a major peak that was assigned to GPC. The primary effect of the cholinergic drugs on the parasites' phosphate profile appeared to be on the level of GPC. In in vivo studies, decreases in internal GPC concentrations occurred prior to any decrease in the concentration of ATP. The importance of these studies relies on the correct identity of this major 31P-NMR resonance. More recently, the identity of this resonance as GPC was questioned by experimental data obtained from C. elegans dauer larvae using the NMR technique. Because studies from our laboratory suggested that phospholipid metabolism may be intimately connected with the parasite's responses to drugs, the identity of the assigned resonance in the 31P-NMR spectrum as GPC in Ascaris suum was reexamined and found to be correct. Similar studies with C. elegans indicate the presence of both GPC and GPE. PMID- 7776120 TI - The effects of culture-site, depth, season, and stock source on the prevalence of Marteilia refringens in cultured mussels (Mytilus galloprovincialis Lmk.) from Galicia, Spain. AB - Samples of a marteiliad parasite in Mytilus galloprovincialis Lmk. from NW Spain were identified as Marteilia refringens, using light and electron microscopy. The most important lesions in the mussel tissues were found in the digestive tubules at the moment of the release of the sporangia, resulting in a breakage of the epithelial cells of the digestive tubules. The plasmodia of a Marteilia-like organism were also found in the gills, accompanied by a severe host reaction in 1 of the 4,200 examined mussels. The prevalence of the M. refringens parasite was monitored for 4 yr and correlation was found with prevalence, site, and depth of mussel culture. No correlation was found with geographical origin of the mussels. Mussels collected from the inner part of the Ria de Vigo were more frequently infected (38.5%) than those from the middle (29.0%) and outer parts (5.5%). Mussels from 2-m samples showed a higher mean prevalence of M. refringens than those from the 5-m samples (13.3 and 8.3%, respectively). PMID- 7776119 TI - Mitochondrial NADH-->NAD transhydrogenation in adult Hymenolepis diminuta. AB - Adult Hymenolepis diminuta mitochondria catalyze a transhydrogenation reaction between NADPH and NAD and between NADH and NAD. The NADPH-->NAD reaction is catalyzed by an inner membrane-associated pyridine nucleotide transhydrogenase, whereas the NADH-->NAD reaction is ostensibly catalyzed by another system(s). The source(s) of NADH-->NAD activity was evaluated by assessments of its intramitochondrial distribution and thermal lability and by comparisons with the distribution/thermal lability of NADH dehydrogenase, lipoamide dehydrogenase, and NADPH-->NAD transhydrogenase. The occurrence of NADH and lipoamide dehydrogenase components was readily demonstrable. Like NADPH-->NAD transhydrogenase, NADH dehydrogenase was essentially membrane bound. Lipoamide dehydrogenase and NADH- >NAD activities were, at different levels, in the membrane and soluble fractions. Based on thermal profiles, NADH and lipoamide dehydrogenase differed from each other and from NADPH-->NAD transhydrogenase. Although the NADH-->NAD profile closely paralleled that for lipoamide dehydrogenase, it also was similar to the NADH dehydrogenase profile. Collectively, these data are consistent with the supposition that the H. diminuta mitochondrial NADH-->NAD transhydrogenation reaction is catalyzed by lipoamide dehydrogenase and possibly by NADH dehydrogenase rather than by an independent transhydrogenase system. PMID- 7776121 TI - Secular and seasonal trends of Neospora abortion in California dairy cows. AB - This study was undertaken to determine if the proportion of dairy cow abortions attributable to Neospora sp. infection increased or occurred in a seasonal cycle during a 6-yr period. Abortions caused by Neospora sp. were tallied for all fetuses submitted to the Tulare branch of the California Veterinary Diagnostic Laboratory between January 1985 and December 1990. Regression analysis of 221 cases of Neospora among 762 fetuses submitted showed a weak increasing secular trend (P = 0.053, r2 = 0.05), with predicted monthly proportions at the beginning and end of the 6 yr of 0.16 and 0.33, respectively. Using a Kolmogorov-Smirnov type statistic, comparison of the 12-mo distribution of Neospora sp. cases and a hypothetical distribution of cows at risk of aborting found about 16% of variation in cases was attributable to season (P < 0.01). More cases were found in winter than in summer and early fall. Results indicate that Neospora sp. abortion in California dairy cows is not new or recently emerging and that seasonally related factors influence some of the risk of abortion. Results suggest that Neospora sp. has contributed to the high dairy cow abortion rate for many years, and that seasonally varying exposures may predispose to transmission or recrudescence of infection. PMID- 7776122 TI - Genetic characterization of isolates of Giardia duodenalis by enzyme electrophoresis: implications for reproductive biology, population structure, taxonomy, and epidemiology. AB - The nature and extent of genetic variation in Giardia was used to infer its mode of reproduction, population structure, taxonomy, and zoonotic potential. Ninety seven isolates of Giardia duodenalis, from a defined area in Western Australia and throughout Australia and overseas, were obtained from humans, cats, cattle, sheep, dogs, goat, beaver, and rats. Enzyme electrophoresis revealed extensive genetic variation with 47 different zymodemes. The widespread occurrence of certain zymodemes and the similarity of relationships among isolates inferred from independent genetic markers suggests a clonal population structure for G. duodenalis, although occasional bouts of genetic exchange may occur. The 47 zymodemes clustered similarly in phenetic (UPGMA) and phylogenetic (Fitch Margoliash) analyses. The level of genetic diversity in isolates from a defined geographical area in Western Australia was similar to the level of diversity in isolates from throughout Australia. These data suggest that clonal lineages within G. duodenalis are evolutionarily independent. Although there was a significant overall correlation between genetic distance separating zymodemes and occurrence in different host species, we found genetically identical isolates from humans and other animals and extensive genetic diversity between isolates from humans. We interpret this as evidence for zoonotic transmission of the parasite. PMID- 7776123 TI - Genetic structure of midwestern Ascaris suum populations: a comparison of isoenzyme and RAPD markers. AB - Isoenzyme and random amplified polymorphic DNA (RAPD) markers were used to characterize the genetics of geographic variation among population samples of Ascaris suum from midwestern localities. Independent estimates of fixation indices (FST) based on isoenzyme and RAPD markers showed the same general patterns of differentiation and substantial statistical correlation (r = 0.70). Of the total estimated gene diversity, 9.4% (isoenzyme) and 9.2% (RAPD) was distributed among infrapopulations. Geographic localities accounted for 7.8% (isoenzyme) and 6.2% (RAPD) of the total gene diversity. Only infrapopulations from a single farm were characterized by low fixation indices (isoenzyme and RAPD FST < 0.05). Isoenzyme and RAPD markers revealed moderate genetic differentiation among infrapopulations and localities, which indicates significant population subdivision among A. suum from farms within geographic regions. Departures from random mating were revealed by deficiencies of heterozygotes within infrapopulations and by high positive values of FIS among and between infrapopulations. The average inbreeding (FIS) coefficient among all infrapopulations was 0.22. Thus, the genetic composition of these A. suum infrapopulations, whether from a general geographic region of a single farm, was not consistent with a model of random recruitment from a larger panmictic pool of parasite life cycle stages. PMID- 7776124 TI - Microevolution and the genetic structure of parasite populations. AB - The development of polymerase chain reaction-based methods for assessing the genotypes of small individual organisms will promote groundbreaking investigations of the genetic architecture of parasite populations. Both quantitative genetic models and general knowledge of parasite natural history are useful for making general predictions about the distribution of genetic variation over geographic space. However, designing experimental studies to assess relationships between specific life history variables and patterns of genetic structure in natural populations will be challenging. Traditional biochemical genetic methods have already been used to study a limited number of parasite populations, and inferred patterns of genetic structure are distinctly different between certain species. Some of these differences in genetic architecture may be explained by parasite or host factors that either promote or retard the dissemination of life cycle stages over geographic space. Many additional empirical studies are needed to characterize basic features of parasite populations, including the spatial distribution and group size of random mating populations and levels of gene flow among parasite subpopulations. PMID- 7776125 TI - A new method for evaluating experimental cryptosporidial parasite loads using immunofluorescent flow cytometry. AB - A flow cytometric method for the quantification of Cryptosporidium parvum oocysts in stool specimens was developed to replace conventional microscopic immunofluorescent assays. Fecal pellets were collected from control (uninfected) severe combined immune-deficient mice, suspended in 2.5% potassium dichromate at a ratio of 400 microliter per pellet, and homogenized by vortexing. Purified oocytes were added to the samples (10(5), 10(4), 10(3), and 10(2)/ml). Aliquots (200 microliters) of the vortexed samples were centrifuged over microscale discontinuous sucrose gradients. The oocyst-containing fractions were collected, washed, and incubated with an oocyst-specific monoclonal antibody (labeled with fluorescein isothiocyanate) for 30 min at 37 degrees C. Sample volumes were adjusted to 600 microliters with phosphate-buffered saline and assayed by using logical gating of forward/side scatter and fluorescence signal on a flow cytometer. Seeded samples showed a linear correlation with the number of oocysts recovered from the gradients. Analyses of stool samples from chronically infected mice demonstrated that the flow cytometry method was approximately 10 times more sensitive than conventional immunofluorescent assays. PMID- 7776126 TI - Duration of immunity to shedding of Toxoplasma gondii oocysts by cats. AB - Cats that have shed Toxoplasma gondii oocysts are considered to be immune to reshedding of oocysts. To investigate if this immunity persists in cats for 6 yr, 12 4-6-mo-old cats without T. gondii antibodies were inoculated orally with tissue cysts of the ME-49 strain (6 cats) and the TS-2 strain (6 cats) of T. gondii. All of them shed > or = 20 million oocysts between 4 and 13 days after feeding tissue cysts. Two cats became ill between 11 and 13 days after primary infection; 1 died on the 13th day, and the other had to be killed on the 11th day because of generalized acute toxoplasmosis. Toxoplasma gondii oocysts were not found on the hair of 10 cats examined 7 days after cats had shed millions of oocysts. On day 39 after primary infection, 5 cats (2 infected with the ME-49 strain and 3 infected with the TS-2 strain) were challenged orally with tissue cysts of the ME-49 strain. None of the challenged cats shed oocysts. One cat died due to causes unrelated to toxoplasmosis. Seventy-seven months after primary infection, the remaining 9 cats were challenged orally with tissue cysts of the P89 strain of T. gondii. Four of these 9 cats re-shed T. gondii oocysts; 3 of them had been challenged also at 39 days after primary infection. Two control cats housed together with chronically infected cats for 6 yr remained seronegative for T. gondii; both of these shed oocysts after challenge with the P89 strain. PMID- 7776127 TI - Detection by ELISA of circulating anti-blood fluke (Carettacola, Hapalotrema, and Learedius) immunoglobulins in Hawaiian green turtles (Chelonia mydas). AB - An enzyme-linked immunosorbent assay (ELISA) is described utilizing the surface glycocalyx crude antigen of adult blood trematodes Learedius learedi, Hapalotrema dorsopora, and Carettacola hawaiiensis, for the detection of circulating antibodies (Ab) in Hawaiian green turtles (Chelonia mydas) naturally infected with the parasites and with or without green turtle fibropapillomatosis (GTFP). A concentration of 10.0 micrograms/ml of antigen was optimal in terms of test specificity and sensitivity. A direct ELISA with anti-reptilian/amphibian phosphatase-labeled IgG identified C. mydas Ab at a dilution of 1/12,800. Utilizing indirect ELISA, it was possible to detect Ab to blood flukes at a dilution of 1/3,200. The gross lesions and histopathology were typical for cardiovascular spirorchidiasis in C. mydas. No significant relationship was found between the size of turtles and the degree of GTFP severity. Forty-seven of 59 (80%) samples, from 5 sites, gave a positive ELISA reaction; 6 of the 47 (13%) specimens gave significantly (P < 0.001) higher absorbance values, with 5 from the same location. All 12 (20%) ELISA-negative turtles originated from 1 site, and the absorbance values of the 41 animals from this location were significantly lower (P < 0.015) when compared with the other 4 sites. The proposed assay is fast, has the feature of visual scoring, and can be used for determination of exposure of C. mydas to the spirorchid trematodes. PMID- 7776128 TI - A defined antigen for the serodiagnosis of Taenia ovis infections in dogs. AB - The evaginated scolex of Taenia ovis secretes an antigen complex into defined culture medium that has been used to develop a cestode-specific enzyme-linked immunosorbent assay (ELISA). We now describe an immunoblot test for antibodies to T. ovis based on the recognition of a 94-kDa antigen band in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile of T. ovis scolex secretions. The test was specific for cestode infections in dogs and was 82% sensitive for the recognition of T. ovis infections. Affinity-purified antibody uniquely recognizing this 94-kDa band was used to screen a cDNA expression library constructed utilizing mRNA from newly evaginated T. ovis scoleces. The cDNA from putative positive bacteriophage were subcloned into the plasmid pGEX and expressed as fusion proteins with schistosome glutathione-S-transferase (GST). The expressed fusion proteins were purified using glutathione-agarose beads. The recombinant parasite antigen was either eluted as a fusion protein with GST or cleaved from GST using a restriction protease. Some dog sera reacted with the GST molecule. However, the recombinant cleaved antigen from 1 clone, T. ovis 40, showed 42% sensitivity and 100% specificity for cestodes in an ELISA using test sera from dogs monospecifically infected with T. ovis and preabsorbed with bacteria. Some sera from dogs monospecifically infected with other cestode species (Taenia pisiformis, 30%; Taenia hydatigena, 30%; Echinococcus granulosus, 20%) reacted with the cloned antigen. PMID- 7776130 TI - High energy phosphate metabolites observed by NMR in infective larvae of Haemonchus contortus. AB - Phosphorus resonances consistent with phosphoarginine and ATP were observed in the in vivo 31P-nuclear magnetic resonance (NMR) spectra of infective larvae of Haemonchus contortus. The level of phosphoarginine quickly declined when nematode suspensions were purged with nitrogen and was restored upon return to aerobic conditions. Saturation transfer NMR demonstrated forward and reverse exchange of phosphorus between phosphoarginine and ATP. PMID- 7776129 TI - Effects of dehydroepiandrosterone in immunosuppressed adult mice infected with Cryptosporidium parvum. AB - Cryptosporidiosis is a diarrheal disease in humans and other animals caused by the coccidian parasite, Cryptosporidium parvum. This study was undertaken to determine the effectiveness of dehydroepiandrosterone (DHEA) in reducing C. parvum infections in immunosuppressed adult C57BL/6N mice and to identify the immunomodulatory effects of DHEA that result in increased resistance to cryptosporidiosis. Dexamethasone-immunosuppressed mice were readily infected with C. parvum following orogastric intubation with 10(6) oocysts/mouse. DHEA treatment of these mice significantly reduced (P < 0.01) both fecal oocyst shedding and parasite colonization of the ilea. Immunosuppressed mice treated with DHEA had more splenic total T cells, CD4+ T cells, and CD8+ T cells than immunosuppressed mice that were not treated, but the differences were not always significant. Moreover, nonimmunosuppressed mice treated with DHEA had significantly more (P < 0.05) splenic total T cells, CD4+ T cells, and total B cells than nonimmunosuppressed mice that did not receive DHEA. Of particular interest was the significantly larger (P < 0.05) number of CD8+ T cells in immunosuppressed, C. parvum-infected, DHEA-treated mice compared with the same mice that were not treated. Up-regulation of the immune system by exogenous DHEA may be useful in the treatment and palliation of cryptosporidiosis. PMID- 7776131 TI - Taxonomy of Heterocotyle dasyatis n. comb. (syn. Diploheterocotyla dasyatis) (Monogenea: Monocotylidae). AB - The monotypic genus Diploheteocotyla Yamaguti, 1965, parasitic on the gills of a dasyatidid ray collected off Hawaii, is synonymized with Heterocotyle Scott, 1904. Its type species, D. dasyatis Yamaguti, 1965, is redescribed, illustrated, and transferred to Heterocotyle as H. dasyatis (Yamaguti, 1965) n. comb. Heterocotyle dasyatis is distinguished from the 9 known species of the genus by the morphology of the male copulatory organ, by the accessory piece, which is composed of 10 sclerotized strands, and by the presence of a complex sclerite in the proximal portion of the vagina. The apparent presence of spermatophores is recorded for the first time in this genus. PMID- 7776133 TI - Myxobolus cultus n. sp. (Myxosporea: Myxobolidae) in the goldfish Carassius auratus transformed from the actinosporean stage in the oligochaete Branchiura sowerbyi. AB - A new myxosporean Myxobolus cultus n. sp. was found in experimentally infected goldfish Carassius auratus exposed to actinosporean spores from the oligochaete Branchiura sowerbyi (Tubificidae). At 2-4 mo following initial exposure, spores of M. cultus were observed in the cartilage of goldfish. A lymphocytic infiltrate surrounded the pseudocysts. Some pseudocysts were destroyed and spores had been engulfed by phagocytes. Phagocytized spores were also found in the epidermis of skin and within melanomacrophage centers in the kidney. PMID- 7776132 TI - Proterometra autraini n. sp. (Digenea: Azygiidae) from Michigan's upper peninsula and a key to species of Proterometra. AB - Life stages of Proterometra autraini n. sp. (Digenea: Azygiidae) from the Au Train River, Au Train, Michigan are described, with emphasis on the cercarial stage. Progenetic cercariae develop in rediae in the snail Elimia livescens and emerge seasonally from mid-summer to mid-autumn. Cercariae emerge naturally between 1000 and 2100 hr EDT. Adults were retrieved from several naturally infected fish species. Specimens of Cottus bairdi (n = 16) displayed the greatest prevalence (75%), mean intensity (7.1), and abundance (5.3) of infection. Experimental infections were successful in C. bairdi, Lepomis macrochirus, and Perca flavescens. The geographical range of this parasite is limited to the portion of the Au Train River between Au Train Lake and Lake Superior. PMID- 7776134 TI - Inhibitory activity of the anti-malarial atovaquone (566C80) against ookinetes, oocysts, and sporozoites of Plasmodium berghei. AB - Ookinete formation from mature Plasmodium berghei gametocytes in vitro was partially inhibited by 0.05-0.1 microM atovaquone and almost totally blocked at a concentration of 0.25 microM. Microgametocyte exflagellation was not affected by atovaquone at concentrations up to 300 microM. Ookinete formation was also inhibited in culture when addition of 0.20 microM atovaquone was delayed by 4 hr, by which time DNA replication was likely to have been completed. Inhibition of ookinete formation by atovaquone was not reversed by orotic acid. Plasmodium berghei-infected Anopheles stephensi mosquitoes were fed a second blood meal 4, 7, 14, and 20 days postinfection (p.i.) from mice that had been treated with atovaquone or control diluent 8 hr previously. Atovaquone blood feeds on day 4 reduced oocyst numbers on days 6-12, although sporozoite numbers in the thorax and abdomen on day 20 were not significantly reduced. Blood feeds on day 7 slowed oocyst growth, blood feeds on day 14 did not significantly reduce sporozoite numbers, and feeds to mosquitoes on day 20 p.i. had no effect on transmission to naive mice. Sporozoite invasion of human hepatoma cells was unaffected by the presence of atovaquone. PMID- 7776135 TI - Ultrastructural effects of diclazuril against Toxoplasma gondii and investigation of a diclazuril-resistant mutant. AB - Diclazuril is an anticoccidial that inhibits tachyzoite production of the RH strain of Toxoplasma gondii by > 97% at a concentration of 0.005 micrograms/ml. The effects of 1.0 microgram/ml diclazuril on the development of 3 strains (RH and 2 tissue cyst formers, GT-1, and WTD-3) of T. gondii in vitro was examined using transmission electron microscopy. The effects of diclazuril were not noted until 2 days after treatment. Treatment with diclazuril interfered with endodyogeny and resulted in the production of multinucleate (> 2 nuclei) meront stages. Up to 12 nuclei were observed in some meronts. Tachyzoites attempted to bud from the surfaces of these stages but division was apparently blocked by the action of diclazuril. The parasitophorous vacuole (PV) enclosing developing stages became hypertrophic. As the meront stages degenerated the PV became filled with membranous material and the cytoplasmic contents of lysed stages. Formation of tissue cysts by the GT-1 and WTD-3 strains of T. gondii was not prevented by treatment with diclazuril. A mutant of the RH strain that was resistant to 1.0 microgram/ml diclazuril was selected by progressive culture in permissive levels of the agent. This DicR-1 mutant produced significantly fewer tachyzoites (P < 0.05) in vitro than its parent strain. Resistance to diclazuril appears to be stable because reversion to sensitivity to the agent did not occur after 50 passages in the absence of drug pressure. The DicR-1 mutant was somewhat less pathogenic for mice (70% mortality) than its parent RH strain (100% mortality) and persisted as tissue cysts in the brains of mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776136 TI - Scanning electron microscopy of adult Wuchereria bancrofti (Nematoda: Filarioidea). AB - Despite the great importance of Wuchereria bancrofti in causing human lymphatic filariasis, only conventional morphological studies have been completed with adult forms of this filaria. No ultrastructural studies have been carried out, mainly due to the difficulty in obtaining viable parasites from human tissues and the lack of a suitable experimental model or in vitro cultivation. With the recent success in using ultrasound to localize adult worms in living tissues and their surgical recovery from human lymphatic vessels, we show in the present paper the first ultrastructural observations of this filarial form. The cuticle surface analyzed by scanning electron microscopy showed a transversal striated aspect with periodic annulations and many small protuberances irregularly distributed along the filaria. The adults present a specialized cephalic area, with the oral opening surrounded by a circular mouth, papillae, and amphidial opening. Other structures, for example the anal, vulvar, and cloacal opening and spicules, were also observed and are described herein. PMID- 7776137 TI - Comparative morphology of the scolices and microtriches among five species of Tetrabothrius (Eucestoda: Tetrabothriidae). AB - The structure of the scolex, neck, and adjacent strobila of 5 species of Tetrabothrius was evaluated using low to high magnification scanning electron microscopy. Species-specific patterns and morphotypes (spiniform, papilliform, and filiform) of microtriches were found on the scolices and strobilar tegument of Tetrabothrius (Oriana) affinis, Tetrabothrius (Oriana) filiformis, and Tetrabothrius (Culmenamniculus) laccocephalus; microtriches were absent in Tetrabothrius (Culmenamniculus) cylindraceus and Tetrabothrius (Tetrabothrius) sp. The presence, distribution, and form of microtriches may not be correlated with the subgeneric divisions of Tetrabothrius or the host taxon. Unique patterns do not appear to be shared with other groups of cestodes, particularly other tetraphyllideans. We suggest that the spiniform, filiform, and papilliform types of microtriches may be symplesiomorphic for the Eucestoda. PMID- 7776138 TI - Multiple heterogenous isolates of Cryptosporidium serpentis from captive snakes are not transmissible to neonatal BALB/c mice (Mus musculus). AB - Oral inoculations of 9 litter-groups of 3 5-day-old suckling BALB/c mouse pups (Mus musculus) with 6.7 x 10(3) to 1.2 x 10(5) per pup of viable, Cryptosporidium serpentis oocysts from snakes resulted in no transmission. Mice showed normal development; the litter-group weight gain was not altered significantly (P > 0.05) relative to the total number of C. serpentis oocysts inoculated or to the initial group weight (P > 0.05). Histological sections of stomach, duodenum, jejunum, ileum, cecum, and colon 4 days postinoculation did not contain life cycle stages of Cryptosporidium in any inoculated mice. Because these neonatal, C. parvum-susceptible BALB/c mice were resistant to infection it is unlikely that C. serpentis transmission to the snakes "via infected prey" results when captive snakes are maintained on a diet of BALB/c mice. PMID- 7776139 TI - New host records for Myxidium serotinum (Protozoa: Myxosporea) from North American amphibians. AB - Three hundred twenty-five amphibians (80 salamanders, 245 frogs and toads) from Arkansas and Texas, representing 28 species within 9 families (Ambystomatidae, Plethodontidae, Salamandridae, Sirenidae, Bufonidae, Hylidae, Leptodacytlidae, Microhylidae, Ranidae) were examined for gall bladder myxosporeans. Of these, 32 (10%) were found to harbor Myxidium serotinum Kudo and Sprague, 1940, including 3 (4%) of the salamanders and 29 (12%) of the frogs and toads. This report documents 6 new host records for M. serotinum in Ambystoma opacum, Bufo americanus charlesmithi, Bufo speciosus, Acris crepitans blanchardi, Gastrophryne olivacea, and Pseudacris streckeri illinoensis. In addition, the Great Plains narrowmouth toad G. olivacea represents the first microhylid host of Myxidium spp. worldwide. PMID- 7776140 TI - Rhabdochona cotti (Nematoda: Rhabdochonidae) in mottled sculpins, Cottus bairdi, from the Ford River, Michigan. AB - A total of 933 mottled sculpins, Cottus bairdi Girard (Cottidae), was examined for Rhabdochona cotti from April 1983 through November 1986 from 3 localities (up river, middle, down-river) in the Ford River in Michigan's Upper Peninsula. The prevalence and mean intensity of R. cotti were highest in sculpins from the middle (37%) and up-river localities (2.0), respectively. The intensity of R. cotti significantly increased with host length at the middle and down-river localities. Rhabdochona cotti did not exhibit consistent seasonal infection patterns at each location when the data were analyzed seasonally within and between years. Gravid R. cotti infected sculpins in most seasons of each year at the up-river and middle localities. The limited occurrence of R. cotti in sculpins in North America is summarized and discussed. PMID- 7776141 TI - B lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi. AB - Immunocompetent mice are resistant to the growth and development of human lymphatic filarial parasites, including the aperiodic strain of Brugia malayi. We have recently established that mice homozygous for the severe combined immunodeficiency (scid) mutation, and therefore deficient in both T and B lymphocytes, are permissive for infection. This observation suggests that components of the adaptive (antigen-specific) immune system are obligate requirements for murine resistance to B. malayi. In order to determine more precisely the component of the immune system that mediates murine resistance to B. malayi, we have used mouse strains in which individual genes involved in the maturation of specific components of the immune system have been disrupted by homologous recombination. In previous studies, we demonstrated that mice that lack either major histocompatibility (MHC) class I restricted, CD8+ T lymphocytes (beta 2-microglobulin knockout mice; beta 2M-/-) or CD4+ T lymphocytes (CD4 knockout mice; CD4-/-) are as resistant to B. malayi as intact mice. In the current study, we have used mice in which the membrane exon of the immunoglobulin (Ig) mu (heavy chain) constant region gene segment has been disrupted by homologous recombination. These mice cannot develop mature B lymphocytes and lack serum Ig. We demonstrate that such "B-less" mice are completely resistant to B. malayi. These data, taken in combination with the observation that T-cell deficient athymic mice homozygous for the nu (nude) mutation are fully permissive for infection, suggest that B lymphocytes and their products are neither required nor sufficient to mediate resistance to B. malayi. PMID- 7776142 TI - Intracapsular asexual proliferation of Mesocestoides sp. tetrathyridia in the gastrointestinal tract and mesenteries of the prairie rattlesnake (Crotalus viridis viridis). AB - Nonproliferous and proliferous tetrathyridia (Mesocestoides sp.) have been reported from natural and experimental infections in reptiles and rodents. Multiple tetrathyridia (1+) in individual capsules (host-derived) were observed for both types of tetrathyridia and in both types of animals. To determine whether proliferous tetrathyridia in this genus could replicate in host capsules of the prairie rattlesnake (Crotalus viridis viridis), 11 snakes were inoculated and maintained in 2 environmental chambers (25 C and 30 C). One snake at each temperature was removed at 4-wk intervals and killed. Sections of the gastrointestinal tract and adjacent mesenteries were histologically examined. The increase in the numbers of tetrathyridia per capsule was significant at both 25 C (P = 0.007) and 30 C (P < 0.001). Identification of 7 intracapsular tetrathyridia with binary scoleces served as collaborative evidence. This paper presents the first significant evidence for asexual replication of the proliferous tetrathyridia (Mesocestoides sp.) in a reptilian host. PMID- 7776143 TI - Andracantha tunitae (Acanthocephala) in the shag (Phalacrocorax aristotelis) from Shetland, Scotland. AB - Following the wreck of the oil tanker Braer on the coast of Shetland, Scotland, in January 1993, many shags (Phalacrocorax aristotelis) were killed. Sixty-nine per cent of these birds were found to harbor a sexually mature acanthocephalan (5 +/- 4.3 [SE] worms per infected bird) in their small intestines. The acanthocephalan has been identified as Andracantha tunitae (= Corynosoma tunitae) on the basis of its characteristic fields of trunk spines and their distribution in the region of the genital aperture. PMID- 7776144 TI - Distribution of Myxobolus scleroperca (Myxobolidae: Myxosporea) in yellow perch (Perca flavescens) in the Great Lakes. AB - Myxobolus scleroperca infected the sclerotic cartilage of 26 of 100 yellow perch (Perca flavescens) examined in August-September 1991 from the Indiana waters of southern Lake Michigan. The mean lengths of infected and uninfected fish were 171 mm and 148 mm, respectively. A significantly higher percentage of female fish were infected than male because more larger females were examined than males. Perch less than 94 mm were not infected, indicating that the parasite is not evenly distributed in the host population, preferring larger (older) fish. An alternative explanation that should be considered is that young fish die from this infection. Yellow perch collected from eastern Lake Michigan in 1990 and from Saginaw Bay, Lake Huron in 1991 were not infected with M. scleroperca, indicating that the parasite has a patchy distribution among perch populations of the Great Lakes. PMID- 7776145 TI - Family beliefs among adolescents at risk for substance abuse. AB - This study investigates the extent to which adolescents identified as at-risk for substance abuse express different beliefs about the importance of family, religiosity, education, and work in comparison to their own parents and to adolescents and parents in control group. It was hypothesized that the success of parents in communicating such values to their children could be a significant variable in risk of substance abuse. We found that parents of at-risk adolescents did not hold significantly different beliefs than parents in the control group. Beliefs of the at-risk adolescents were significantly different from other adolescents and both parent groups. We also found that the absolute difference in age between parent and adolescent significantly smaller in the at-risk group as compared to the control group. PMID- 7776146 TI - Impact of contextual variables on adolescent situational expectation of substance use. AB - The relationship between contextual variables and situational expectation of drug and alcohol use at the school level suggested by Interactive theory was investigated [1, 2]. A canonical correlation analysis supported a significant relationship between situational expectation of drug and alcohol use and several contextual variables including Students' Perceptions of What Teachers Expect of Them Academically, Percentage of White Students, and the Prosperity of the School. The results indicated that the more prosperous the school and the greater the students' perceptions of what teachers expect of them academically, the lower the situational expectation of smoking cigarettes or taking depressants and the higher the percentage of white students the higher the situational expectation of drinking beer and liquor. Implications for prevention programs and school environment are discussed. PMID- 7776147 TI - The relationship of self-perception and stress in adult children of alcoholics and their peers. AB - Woititz identified thirteen generalizations which she asserts characterize adult children of alcoholics (ACOAs) [1]. Her work, however, was based upon clinical populations and may not be generalizable to a non-clinical population. Using 442 undergraduate students, 2 x 3 multivariate analysis of variance (parental alcoholism by level of childhood stress) on students' perceptions of the applicability of Woititz's variables to them was conducted. No significant effects were found even though ACOAs experienced more childhood stress than their peers. Results do not support the generalization of Woitiz's model to a non clinical sample. PMID- 7776148 TI - Effects of normative feedback on consumption among heavy drinking college students. AB - College students, particularly those who drink heavily, tend to overestimate the prevalence of heavy drinking among their peers. A self-regulation model predicts that feedback of undesirable deviation from normative standards would result in correction of behavior toward perceived norms. From a screening of 568 college students, sixty-four heavy drinkers were identified and offered the opportunity to participate in a survey study of drinking. Of these, twenty-six accepted and returned questionnaires with detailed information regarding their drinking practices. These were randomized to receive or not receive, by return mail, personal feedback of their drinking relative to population norms. At an independent follow-up interview, feedback subjects showed greater reduction in weekly consumption and typical intoxication levels, relative to controls. This simple feedback intervention, requiring no personal contact, may be a cost effective strategy for reducing risky drinking. PMID- 7776149 TI - Adolescent drinking and driving: etiology and interpretation. AB - In the adolescent population, drinking and driving is an important cause of injury, disability and premature death. A literature review of the demographics and etiology of drinking and drinking/driving reveals: 1) which subgroups of the adolescent population are more likely to drink and drink/drive; 2) where and why adolescents drink and drink/drive; 3) peer and family issues associated with adolescent drinking and drinking/driving; and 4) adolescent expectancies and perceived efficacies associated with drinking and drinking/driving. A discussion of the role of theory and the use of etiologic data in intervention research precedes an overview of several types of school-based alcohol-prevention programs and recommendations for more theory based interventions. PMID- 7776150 TI - Patterns of drug use among white institutionalized delinquents in Georgia: evidence from a latent class analysis. AB - Previous research by Kandel [1] and others indicates that adolescent drug use follows a progression from legal drugs, through marijuana, to hard drugs. In this study of drug use patterns, institutionalized delinquents were found to follow a similar progression of drug use. Unlike previous studies which used "rule of thumb" methods of model assessment, this study uses probabilistic assessment of the models. Importantly, the present study supports a modified gate-way sequence, where cocaine use appears as an intermediate step between marijuana use and use of other hard drugs. It is suggested that widespread availability of cocaine in the late 1980's may have resulted in a new "step" in the drug use sequence. PMID- 7776151 TI - Reading abilities of drug users in Anchorage, Alaska. AB - Evaluated the reading abilities of 122 male and fifty-nine female intravenous and other drug users in Anchorage, Alaska. Reading abilities were assessed through the Reading subtest of the Wide Range Achievement Test-Revised and the short Form of the Woodcock Reading Mastery Test-Revised. Results indicated that men and Black subjects reported the highest levels of schooling completed. However, no differences were revealed across gender and ethnicity in actual reading levels. Among all subjects, the average reading ability was between 8.5 and 8.7 grade level. These scores place the average subject reading at a level lower than approximately 76 percent of the general population. Implications are provided for development of educational materials accessible for this population. PMID- 7776152 TI - Ultrastructural localization of glycosaminoglycans in human gingival connective tissue using cupromeronic blue. AB - Human gingiva was stained with cupromeronic blue according to Scott's critical electrolyte concentration technique in order to localize glycosaminoglycans (GAG) in the electron microscope. Identification was performed by digestion with chondroitinase AC, ABC and heparinase. The GAG were localized in three compartments of the connective tissue: the supra-alveolar fiber apparatus, the loose connective tissue and the basement membranes. In the supra-alveolar fiber apparatus, consisting mainly of densely packed parallel collagen fibrils, dermatan sulfate GAG are regularly attached to the d-band of the collagen fibrils. The precipitates (6-7 nm in diameter) aggregate to thicker precipitates (up to 16 nm), thus possibly providing stability to the fiber system. In the loose connective tissue with sparse collagen fibrils dermatan and chondroitin sulfate GAG form very large precipitates (up to 30 nm in diameter and 400 nm length) which interconnect the few collagen fibrils. The basement membranes of the epithelium and capillary endothelium contain heparan sulfate GAG as fine precipitates (4-6 nm in diameter) which form a meshwork. These findings are consistent with the Scott model (1) for the interactions among glycans and glycans and collagen fibrils in connective tissues. PMID- 7776153 TI - Bacterial steroidogenesis by periodontal pathogens and the effect of bacterial enzymes on steroid conversions by human gingival fibroblasts in culture. AB - Studies were performed to investigate the effect of microbial culture supernatants of periodontal pathogens on the metabolism of radiolabelled testosterone in the presence or absence of human gingival fibroblasts. Subgingival plaque samples were obtained on paper points from 3 sites with probing depth values of 6-8 mm. Samples were incubated with 14C-testosterone for 24 h in brain heart infusion (BHI) broth. Similar incubations were also carried out with strains of A. actinomycetemcomitans, P. Intermedius and P. gingivalis to study the metabolism of radiolabelled testosterone by these periodontal pathogens. At the end of a 24 h incubation period with fibroblasts and supernatants or sonicates, the radioactive metabolites were extracted with ethyl acetate, evaporated and subjected to thin layer chromatography. The separated metabolites were quantified by scanning the radioactive plates using a Berthold linear analyser. When three sub-gingival plaque samples were incubated with radiolabelled testosterone there were 50-fold, 10-12-fold and 15-17-fold increases in 5 alpha-dihydrotestosterone (DHT) synthesis over 4-androstenedione production in these mixed microbial cultures. The two strains of P. intermedius produced 3- and 20-fold increases in 4-androstenedione production and DHT synthesis respectively. Both strains of A. actinomycetemcomitans and P. gingivalis showed 3-4-fold and 12-28-fold increases respectively in 4 androstenedione synthesis over that of DHT. Culture supernatants of P. intermedius and P. gingivalis caused 3-fold and 2-fold increases in DHT synthesis by fibroblasts over controls. There was little change in the case of the third pathogen. Since DHT has implications on matrix synthesis by fibroblasts in the environment of plaque associated inflammatory periodontal disease, bacterial metabolism and the effect of bacterial supernatants on human gingival fibroblasts can influence the degree of inflammatory repair. PMID- 7776154 TI - Effect of Campylobacter rectus LPS on plasminogen activator-plasmin system in human gingival fibroblast cells. AB - The plasminogen activator (PA)-plasmin system is implicated in the degradation of the extracellular matrix in inflammation through activation of metalloproteases and prekallikrein. We examined the activation of the PA-plasmin system in human gingival fibroblast cells (Gin-1 cells) following treatment with lipopolysaccharide (LPS) from Campylobacter rectus, which is frequently detected at sites of periodontal disease. The C. rectus LPS stimulated the plasmin activity in the conditioned medium of Gin-1 cells in a time- and dose-dependent manner, and C. rectus LPS also stimulated the PA activity in the conditioned medium. The PA produced by Gin-1 cells was determined to be urokinase PA (uPA), as preincubation of Gin-1 conditioned medium with anti-uPA antiserum completely inhibited the PA activity while that with anti-tPA antiserum had no inhibitory effect. The concentration of PA inhibitor-1 (PAI-1) in the conditioned medium was decreased by the addition of C. rectus LPS. Therefore, the enhancement of plasmin activity in the conditioned medium was dependent on increased uPA activity via the decrease of the PAI-1 level of Gin-1 cells treated with C. rectus LPS. Furthermore, the conditioned medium of Gin-1 cells treated with C. rectus LPS showed significantly increased kallikrein activity, indicating the conversion of prekallikrein to kallikrein, which converts kininogen into kinin. These findings suggest that C. rectus LPS is a potent stimulator of inflammation of gingival tissue which acts through stimulation of the PA-plasmin system. PMID- 7776156 TI - Determination of small sample volumes in the analysis of drugs at specific sites in the oral cavity. AB - Two methods for the determination of sample volumes between 0.2 and 0.6 microliters were compared by preparing standard curves for volumes over this range. The first method used a Periotron and the second the sample mass. A linear model was fitted and 95% confidence limits for volumes estimated by each method were calculated. This showed that use of either the maximum Periotron reading or the sample mass allowed estimation of volumes to within +/- 0.056 microliter and +/- 0.047 microliter respectively. It is proposed that measurement of sample mass provides a simple and accurate method to determine sample volume when analysing drug concentrations at specific sites in the oral cavity. PMID- 7776155 TI - Cytotoxic effect of vesicles produced by Porphyromonas gingivalis on fibroblasts in culture. AB - It has been shown that the vesicles produced by Porphyromonas gingivalis under certain growth conditions contribute to its pathogenicity. In this study, we demonstrate the cytotoxic effect of the vesicles using two methods: one quantitative (the colorimetric cytotoxicity test using sulforhodamine B) and the other qualitative (flow cytometry). PMID- 7776157 TI - Detection of periodontal probing change by analysis of distribution mean and skew. AB - A problem associated with probing measurement is that important site-specific change may be obscured by measurement variability. Furthermore, if many sites are monitored there is an increasing likelihood that any particular "detected change" might be the result of this measurement error. Since error and multiplicity effects would tend to increase mouth-wise false positive rate, demanding decision thresholds are often set. However, imposition of difficult criteria, increases site-wise false negative rate and therefore reduces utility in the clinical setting. Evaluation of mean change might sometimes be a useful alternative, but also problematic as a few dramatic site-level losses can be inconsequential among many stable or improving sites. A strategy is proposed for evaluating probing changes in a single patient, which is based on the statistical evaluation of two attributes of the change distribution. (1) Disease progression is concluded when mean probing loss increases over time, and (2) a clinically relevant asymmetry is concluded when the distribution tail corresponding to loss is skewed. Computerized simulation was used to determine alpha-error for tests of mean and skew, for three different distributions of probing change. Actual alpha-error was shown to be near nominal levels. Power was estimated as a function of the number and magnitude of sites with probing loss and as a function of whether there was change in both mean and skew or in skew alone. Under most conditions studied, simultaneous tests for skew and mean provided enhanced power relative to a test for loss alone and would appear to offer the clinician an additional statistical context for appraising disease status. PMID- 7776158 TI - Succession of putative peri-implant pathogens after root-form and plate-form implant placement in partially dentate adult monkeys. AB - This report describes the succession of putative peri-implant pathogens in partially dentate monkeys after dental implantation and prosthetic reconstruction. Tooth and implant (6 root-end form, 4 blade-vent implants) sites in eight monkeys were monitored microbiologically and clinically during the pre implant stage, abutment connection stage, bridge placement stage, and three and six months after the bridge placement stage. Tooth and implant sites were cleaned monthly post-extraction. Microbiological studies included dark field microscopy, selective and non-selective culture, and primary phenotypic characterization of culture isolates. After implant surgery, the median proportion of several putative peri-implant pathogens studied were significantly elevated. Following fixture placement, P. intermedia replaced P. melaninogenica as the predominant Black Pigmented Anaerobic Bacilli (BPAB) in the mouth. After abutment connection stage, levels of P. intermedia, A. actinomycetemcomitans, F. nucleatun, Haemophilus sp. and spirochetes were significantly elevated at implant and tooth sites. Three months after bridge installations, P. intermedia and A. actinomycetemcomitans remained significantly elevated at implant sites. At six months after bridge installation, levels of P. intermedia, F. nucleatum and A. actinomycetemcomitans declined significantly relative to levels at three months. Porphyromonas sp. and spirochetes were not significantly elevated although their levels correlated with gingival redness. P. intermedia, Porphyromonas sp. and spirochetes levels correlated significantly with probing depth. Correlation was detected between P. gingivalis and spirochetes; and between A. actinomycetemcomitans and F. nucleatum. Our studies show a transitional increase in levels of several organisms resembling putative pathogens of human peri implant infection, associated with implant placements in partially edentulous mouths and supports early prophylactic interventions to control their levels. PMID- 7776159 TI - Assessment of periodontal tissues damping characteristics: current concepts and clinical trials. AB - The reproducibility of an electronic device for the assessment of periodontal tissues damping characteristics was judged by evaluating the inter-examiner, inter-device and day to day variations of the measurements (PTVs). Nine young periodontally healthy volunteers were examined by two examiners (EX-1 and EX-2) and two devices (D-1 and D-2) in the following sequence: EX-1 D-1, EX-2 D-1, EX-1 D-2, and EX-2 D-2. PTVs were obtained at 5 different occasions during the same day. In some instances examiner 2 measured higher scores than examiner 1 with both devices. This difference was statistically significant (P = 0.05), if the total of 900 measurements was considered. The measurements of device 2 were approximately 0.5 PTV units higher, also reaching a statistical significance (P = 0.05). This difference is of limited clinical significance. The day to day variation was evaluated by comparing the scores obtained at 8 a.m. with the ones at the four other periods. The lowest scores were measured at 8 a.m. Only the 11 a.m. and the 2 p.m. measurements differed significantly. The effect of hormonal changes during the menstrual cycle and of smoking habits on PTVs were also evaluated. Ten female periodontally healthy volunteers were examined three times a week, during a period of two menstrual cycles. No significant PTV changes were found during the menstrual cycle. The effect of the smoking habit on PTVs was tested on 23 periodontally healthy patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776160 TI - An evaluation of laser Doppler readings obtained from human gingival sulci. AB - A small laser doppler probe with an outside diameter comparable to a conventional periodontal probe (0.5 mm) was developed. The objectives of this investigation were to determine if intrasulcular laser doppler readings (LDR): 1) are reproducible; 2) can detect vascular changes associated with trauma from probe placement; 3) were reproducible when obtained with a stabilizing stent or without a stent; and 4) could detect vascular changes following the injection of a local anesthetic with vasoconstrictor. Nine adult volunteers with clinically healthy gingiva were evaluated for 30 second intervals at 5 sites. Baseline LDR were obtained twice at each site utilizing an acrylic stent to stabilize the probe and once without the stent (trial 1). All LDR were repeated at one month (trial 2) and again two months (trial 3) after baseline. One additional reading per subject was obtained following the administration of a local anesthetic with a vasoconstrictor during the second trial. Inter-trial comparisons found no significant difference in mean LDR between any of the three observation times. However, intra-trial comparison between the first and second LDR revealed an increase of approximately 50% in mean LDR. A 3-fold reduction in mean LDR (P < 0.001) was noted following the administration of a local anesthetic with vasoconstrictor. Intra-class correlation coefficients for stent stabilized LDR were 0.51 (P < 0.01) and 0.63 (P < 0.01) while intra-class correlation for hand held LDR was 0.40 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776161 TI - The effects of smokeless tobacco on clinical parameters of inflammation and gingival crevicular fluid prostaglandin E2, interleukin-1 alpha, and interleukin 1 beta. AB - The purpose of this study was to examine the effect of smokeless tobacco (ST) on gingival inflammation as assessed clinically and biochemically by gingival crevicular fluid (GCF) levels of PGE2, IL-1 alpha, and IL-1 beta. These parameters were compared in ST users (n = 12) and control, non-tobacco using subjects (n = 8) matched for plaque and probing depth levels. Both GI and GCF PGE2 concentration were significantly (P < 0.05) elevated at ST placement sites compared to sites in control subjects. A short-term longitudinal trial spanning 7 days also was undertaken within ST users (n = 18) to study the dynamics of gingival inflammation when ST is moved to a new site. At day 0 habitual ST placement sites exhibited a significantly (P < 0.05) higher GI compared to non tobacco placement sites. Following transfer of ST to a new placement site, 48 hour GI scores were increased (P < 0.05) at this region. Although GCF parameters were not significantly altered, over 80% of the subjects developed dramatic inflammatory reactions in the alveolar mucosa, ranging from erythema to ulceration, at the new site of placement. This observation of a more severe response in alveolar mucosa compared to gingiva may be related to the physical location of ST or differences in tissue characteristics. PMID- 7776162 TI - Histological location of a standardized periodontal probe in man. AB - The purpose of this study was to locate the position of the periodontal probe tip using a pressure of 126 N/cm2 (force of 0.30N using a round periodontal probe tip with a diameter of 0.55 mm). The influence of gingival inflammation on this position was also studied. Subjects with three levels of periodontal health and disease were entered into the study and each contributed one experimental tooth. At each site a standardized probing system was used to place a probe into a clinical pocket. The probe tip was luted to the test tooth surface. The tooth with its gingival tissue and probe tip was extracted, fixed, and processed for histological measurements. Distances in mm were obtained from the cemento-enamel junction (CEJ) to the probe tip, to the base of the crevice/pocket, and to the most coronal connective tissue attachment. Analysis of the data indicated that clinical inflammation was not a factor in the placement of the probe tip at crevice/pocket's landmarks relative to the CEJ; however variability of probing may have caused the non-significance. The probing system placed the probe tip 0.66 mm apical to the base of the crevice/pocket and 0.06 mm coronal to the most coronal connective tissue attachment. These conclusions corroborated the results of the previous study in dogs which predicted probe placement of 0.44 mm apical to the base of the crevice using the standardized pressure of this probing system. PMID- 7776163 TI - Removal of interproximal subgingival plaque by hand and automatic toothbrushes. AB - Subgingival plaque removal at interproximal sites by automatic and hand toothbrushes was compared with control sites at which cleansing was not performed. There were 58 patients, 35 to 63 years of age, each with one hopeless tooth requiring extraction. Each patient was randomly assigned to one of four test groups: hand brush; automatic toothbrush 1; automatic toothbrush 2; and no brushing. The brushing instructions as stated by the manufacturers were demonstrated and the patient brushed the sextant containing the test tooth for 20 seconds. The level of the gingival margin was marked at each interproximal test site. The teeth were extracted and processed for SEM, and subgingival plaque was viewed at X100 and X2000 magnifications. A montage of photomicrographs of the gingival groove to the occlusal margin of the bacterial plaque at X100 magnification was made and the distance from the groove to the margin was measured. An ANOVA was performed using P = 0.05 level for significance. Due to processing difficulties, only 33 specimens were available for analysis. The average distances from the groove to the subgingival plaque front for the four test groups were 0.514, 0.132, 0.163, and 0.111 mm respectively. The maximum distance (1.5 mm) of plaque removal was greatest for the hand toothbrush. Due to the large standard deviation (0.636 compared to 0.146, 0.250, and 0.124 respectively), the hand brushing group was excluded from ANOVA. There were no statistically significant differences among the automatic toothbrushes and the no brushing control (P = 0.8393). It was concluded that a single session of oral hygiene instruction with an automatic toothbrush did not result in subgingival interproximal plaque cleansing. PMID- 7776165 TI - Vascular changes following mucoperiosteal flap surgery: a fluorescein angiography study in dogs. AB - This study was undertaken to determine the vascular changes which occur following mucoperiosteal flap surgery where two different suturing techniques were employed. In four healthy adult mongrel dogs, buccal and lingual full-thickness envelope flaps were reflected in the mandibular quadrants following intravicular incisions from the first premolar to the first molar. The flaps were immediately readapted and primary closure was achieved by the horizontal mattress suturing technique in one quadrant and the direct interrupted suturing technique in the contralateral quadrant of each dog. A simple photographic system was developed for recording the in vivo gingival circulation depicted by fluorescein angiography just prior to surgery and then after surgery on days 1, 3, 7, 10, 14, and 21. The flaps were divided into three interproximal and two mid-buccal sites for analysis and the intracapillary and diffusion extent of dye fluorescence was accurately quantified by computerized planimetry. As healing progressed, longitudinal changes relative to presurgical baseline were analyzed by paired t test. Cross-sectional comparisons utilizing Student t-test allowed for evaluating differences between the two suturing techniques as well as differences between interproximal versus mid-buccal sites at each postsurgical day. It was found that the simple act of raising a mucoperiosteal envelope flap initiates significant vascular trauma. Statistically significant reductions in flap circulation relative to presurgical baseline lasted for at least 3 days but persisted for 7 days at the interproximal sites. Flap diffusion (extravascular leakage) recovered sooner and extended over a significantly greater area of the flap than did intracapillary flap circulation during the early period of healing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776164 TI - Use of the carbon dioxide laser in retarding epithelial migration: a pilot histological human study utilizing case reports. AB - Predictable regeneration of tooth-supporting tissues lost to periodontal disease is the aim of periodontal therapy. Often the result of conventional treatment is healing with a long junctional epithelium along the root surface and little regeneration of the complete attachment apparatus. The purpose of this pilot study was to evaluate whether de-epithelialization with a CO2 laser at the time of flap surgery and at 10-day intervals over the first 30 days of healing has the potential to enhance the formation of a connective tissue attachment. Six mandibular incisors in two patients were selected for the study. Each patient received oral hygiene instruction and initial therapy prior to surgery. The teeth were splinted together, open flap debridement was performed on all teeth, a notch was placed on the roots at the height of the crest of the alveolar bone, and the flaps were sutured in place. The test side received controlled de epithelialization of the outer (oral) gingiva with the carbon dioxide laser, and the inner gingival flap. The de-epithelialization was repeated on the test side at 10, 20, and 30 days postsurgically. Controls received open debridement only. Block sections were taken at 90 days and processed for histologic analysis. The results showed that for both patients, junctional epithelium (JE) was formed on both test and control teeth. In all control teeth, the JE extended the entire length of the root to the base of the reference notch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776166 TI - Alendronate treatment of naturally-occurring periodontitis in beagle dogs. AB - The treatment of periodontal disease has been largely directed at the microbiological etiology. The prevention of bone loss by modulating the host response to the bacteria may be a useful adjunctive method in the management of periodontitis. Alendronate, an amino bisphosphonate, may inhibit bone loss in osteolytic diseases by altering osteoclast activity. The objective of this double blind study was to evaluate alendronate inhibition of alveolar bone loss in the naturally occurring beagle dog model of periodontitis. Sixteen 7 to 9 year old beagles with moderate-to-severe periodontitis were studied for 6 months. The dogs were stratified into two groups based on initial periodontal severity. One group received 3.0 mg/kg alendronate weekly orally and the other group received a placebo. Silk ligatures were placed on the study teeth for the first 3 months of the study to exacerbate the periodontal destruction. Clinical data were collected for attachment level, gingival index, plaque index, and mobility at baseline and one-month intervals. Intraoral radiographs were made at baseline and at 3 and 6 months. The mandibles were processed for histology at month 6. The radiographs were analyzed by digital image analysis of the subtracted images. A statistically significant difference in bone mass (P < 0.001) was observed between the alendronate and placebo groups. The bisphosphonate had no effect on the clinical parameters of gingival inflammation or plaque. A trend toward decreased attachment loss and mobility was observed in favor of the alendronate group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776167 TI - The effectiveness of a disposable tooth cleansing device on plaque. AB - A disposable polyester foam sponge on a stick, impregnated with a non-foaming dentifrice, has been widely dispensed to hospitalized and nursing home patients for intraoral cleansing and refreshing. Since no information was found relative to tooth cleansing capabilities, we have evaluated its effectiveness in the removal of accumulated plaque and also in prevention of plaque accumulation. Removal of 72 hours of accumulated plaque was assessed in a cross-over design study comparing the device with a commercially-available toothbrush by two different groups of 13 and 29 adult, healthy subjects who used each instrument for 1 and 3 minutes respectively. No significant differences were found between mean scores assessed by Turesky's modification of the Quigley-Hein plaque index by either group using either instrument at either time period (P > 0.05). Prevention of plaque accumulation was assessed in a third group of 25 subjects who used each instrument an average of 3 times a day for 1 week in a cross-over study. While the toothbrush was found significantly more effective in retarding the accumulation of plaque from a plaque-free baseline on both facial and lingual surfaces (P < 0.02), the tooth cleansing device still retained plaque-preventive capabilities by maintaining plaque formation below 2 mm at the cervical margin of the tooth. Results of this study indicate the tooth cleansing device may be a viable alternative to conventional toothbrushes. PMID- 7776168 TI - Prostaglandin E2 regulates gingival mononuclear cell immunoglobulin production. AB - Histological studies have revealed elevated levels of T and B lymphocytes in inflamed gingival tissue. Functional analysis of these B cells has determined that they are spontaneously secreting large amounts of immunoglobulin. Several components of bacterial plaque which accumulate during the onset of periodontal disease induce polyclonal B cell activation, and are most likely responsible for the "hyperactive" state of these gingival B lymphocytes. In addition to this exaggerated humoral response, increased levels of inflammatory mediators, such as prostaglandin (PG) E2, have been implicated in the pathogenesis of disease. Therefore, the purpose of this study was to determine if PGE2 could regulate immunoglobulin production within inflamed gingival tissue. Specimens were harvested during routine surgery of patients with chronic adult periodontitis. Utilizing an ELISA, elevated levels of IgG were detected in the supernatant of cultured gingival mononuclear cells. Inclusion of indomethacin, which inhibits arachidonic acid metabolites such as PGE2, caused a decrease in IgG levels. PGE2 exerted a biphasic effect upon IgG production, with high doses diminishing and low doses increasing IgG levels. From a clinical perspective, these results suggest that elevated levels of PGE2 associated with inflammation will attenuate an IgG response and, as PGE2 production wanes, the local humoral response will rebound. Interestingly, the combination of low dose PGE2 and IL-4 induced a synergistic rise in IgG production. These findings support the theory that local PGE2 levels can regulate immunoglobulin production and potentiate cytokine induced class switching within gingival tissue. PMID- 7776169 TI - The effects of scaling procedures on epithelial cell growth on titanium surfaces. AB - This study examined in vitro epithelial cell growth on titanium surfaces which had been instrumented by 3 types of periodontal curets. Commercially pure titanium discs were uniformly scaled using plastic, stainless steel, or gold coated curets and then seeded with a microdot (50,000 cells per 10 microliters) of rat gingival epithelial cells. After 5 days of growth, epithelial cell surface area (mm2) coverage was measured on photographed specimens using a computer digitizing system. Scanning electron microscopic evaluation showed a denser central core of cellular growth on the stainless steel-treated surfaces as compared to the other surface treatments. Epithelial surface area coverage on the stainless steel, plastic, and control groups did not vary significantly among groups. However the gold-coated curet exposed surfaces supported significantly less epithelial growth than the stainless steel and control surfaces. A better understanding of in vitro epithelial cell responses to different titanium surface characteristics will assist in designing implant scaling procedures which allow maintenance of the implant perimucosal seal. PMID- 7776170 TI - Short-term effects of phase I therapy on crevicular cell populations. AB - The purpose of the present study was to use a novel intracrevicular lavage technique to evaluate short-term effects of phase I therapy on crevicular cell populations. Nineteen patients with untreated advanced adult periodontitis were selected for phase I therapy. One side of the dentition was treated with ultrasonic curets (U), the other side with manual curets (M). Nine months before (-9), immediately prior to (0), and 1 month after treatment (+1) gingival index (GI), plaque index (PI), bleeding index (BI), bleeding on probing (BOP), probing depth (PD), and probing attachment levels (PAL) were measured at all sites in the dentition. Crevicular lavages were obtained from 3 to 4 selected sites per patient at the same time points. Crevicular leukocytes were vital stained with ethydium bromide-fluorescein-diacetate (EB-FDA). The total number of cells and the percentage of vital cells (%) were calculated for each sample. Clinical and lavage parameters obtained from the selected sites were compared between U and M sites, and between pre- and post-treatment values. The results showed that without treatment PAL remained at the same level at both pretreatment time points -9 and -0 (control). At 1 month after treatment there were statistically significant reductions in GI, PI, BOP, and PD (P < 0.001 for each comparison), and a statistically significant gain in PAL from 4.9 to 4.1 mm (P = 0.014). The total number of leukocytes per sample was similar at both pretreatment time points, but numerically reduced at 1 month after treatment. The percent of vital leukocytes was above 74% at both pretreatment time points (control). After treatment these values were below 70%. This reduction was statistically significant (P < 0.002). These results suggest that periodontal phase I therapy leads to shifts in crevicular cell populations. PMID- 7776171 TI - Factitious injury of the oral mucosa: a case series. AB - Gingival and oral mucosal tissues can be the site of a number of mucocutaneous and ulcerative conditions. Generally, these are not difficult to identify on the basis of clinical characteristics, and diagnosis can be aided by the use of routine histopathological and immunopathological techniques as well as other laboratory investigations. Self-induced or factitious injury (FI) of the oral mucosal tissues may present a confusing clinical picture, and be diagnosed erroneously as a mucocutaneous disorder in spite of the absence of appropriate pathological and immunopathological findings, or a failure to respond to routine treatment. A case series is presented here outlining 4 cases of FI which presented initially as mucocutaneous disease. These cases were investigated to rule out systemic or local causes, in order to establish a diagnosis of FI. Treatment of these conditions was facilitated with placebo or sham procedures which were designed primarily to cover the lesions. In most cases, the self injurious behavior could be linked to secondary gain. PMID- 7776172 TI - Re: A 6-month multi-center evaluation of adjunctive tetracycline fiber therapy used in conjunction with scaling and root planing in maintenance patients (J Periodontal 1993;64:685-691) PMID- 7776173 TI - A review of the evidence supporting melatonin's role as an antioxidant. AB - This survey summarizes the findings, accumulated within the last 2 years, concerning melatonin's role in defending against toxic free radicals. Free radicals are chemical constituents that have an unpaired electron in their outer orbital and, because of this feature, are highly reactive. Inspired oxygen, which sustains life, also is harmful because up to 5% of the oxygen (O2) taken in is converted to oxygen-free radicals. The addition of a single electron to O2 produces the superoxide anion radical (O2-.); O2-. is catalytic-reduced by superoxide dismutase, to hydrogen peroxide (H2O2). Although H2O2 is not itself a free radical, it can be toxic at high concentrations and, more importantly, it can be reduced to the hydroxyl radical (.OH). The .OH is the most toxic of the oxygen-based radicals and it wreaks havoc within cells, particularly with macromolecules. In recent in vitro studies, melatonin was shown to be a very efficient neutralizer of the .OH; indeed, in the system used to test its free radical scavenging ability it was found to be significantly more effective than the well known antioxidant, glutathione (GSH), in doing so. Likewise, melatonin has been shown to stimulate glutathione peroxidase (GSH-Px) activity in neural tissue; GSH-PX metabolizes reduced glutathione to its oxidized form and in doing so it converts H2O2 to H2O, thereby reducing generation of the .OH by eliminating its precursor. More recent studies have shown that melatonin is also a more efficient scavenger of the peroxyl radical than is vitamin E. The peroxyl radical is generated during lipid peroxidation and propagates the chain reaction that leads to massive lipid destruction in cell membranes. In vivo studies have demonstrated that melatonin is remarkably potent in protecting against free radical damage induced by a variety of means. Thus, DNA damage resulting from either the exposure of animals to the chemical carcinogen safrole or to ionizing radiation is markedly reduced when melatonin is co-administered. Likewise, the induction of cataracts, generally accepted as being a consequence of free radical attack on lenticular macromolecules, in newborn rats injected with a GSH depleting drug are prevented when the animals are given daily melatonin injections. Also, paraquat-induced lipid peroxidation in the lungs of rats is overcome when they also receive melatonin during the exposure period. Paraquat is a highly toxic herbicide that inflicts at least part of its damage by generating free radicals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776174 TI - Age-related differences in the structure of human pineal calcium deposits: results of transmission electron microscopy and mineralographic microanalysis. AB - Pineal tissue calcifications (male, ages 14, 47, 62, 82), which were metallographically embedded and polished at controlled levels and studied by transmission electron microscopy and microanalytic spectroscopy, showed age related differences. Results show that concentrically arranged crescent-shaped lamellae increase in number and decrease in width with age. Calcium (Ca) and phosphorus (P) per point measurements in dark and light lamellae at various distances from the core show Ca/P molar ratios between 1.49-1.62 in the 82-year old specimen as compared to 1.26 to 1.41 in the younger specimens. The 62-year old specimens show a decrease in P and an increase in Ca from periphery to center. These data and other descriptive details suggest that the sum of these changes represent remodelling of the mineralogical structure within the same calcification throughout the life span. PMID- 7776175 TI - Effects of a one-hour light pulse on the timing of the circadian rhythm in melatonin secretion in rams. AB - The effects of a 1-hr light pulse on the timing of the circadian rhythm in the blood plasma concentration of melatonin were documented in Soay rams. Groups of 5 to 6 animals were transferred from short days (LD 8:16) to constant dim red light (DD) for 6 days, and were exposed to a 1-hr light pulse at one of 16 different times throughout 24 hr on day 3. Blood samples were collected hourly for 30 hr before (day 2-3) and after the light pulse (day 5-6), and the plasma concentrations of melatonin were measured by radioimmunoassay. The animals were allocated to experimental groups based on the circadian time (CT) when the light pulse was given using two hourly blocks through the circadian day; the onset of enhanced melatonin secretion (melatonin peak) was designated as CT 12. Under DD there was a clearly defined plasma melatonin rhythm in all animals. The mean duration of the melatonin peak was 13.24 +/- 0.16 hr (n = 91) and the mean period between the onset of successive melatonin peaks was 23.55 +/- 0.10 hr (n = 21). The effect of the 1-hr light pulse on the time of onset of the melatonin peak varied significantly with the circadian time when the light pulse was given (ANOVA, P = 0.031).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776176 TI - Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry. AB - Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage. PMID- 7776177 TI - The pineal gland of the aging rat: calcium localization and variation in the number of pinealocytes. AB - In the present study, we investigated the population of pinealocytes in the pineal gland of aging rats. Dark and light pinealocytes were analyzed as to their calcium content. Calcium localization was realized in dark and light cells by means of cytochemistry and X-ray microanalysis. Calcium was mainly localized in dark pinealocytes characterized by many ultrastructural signs of degeneration. The number of pinealocytes per square surface of aged rats (28 months) was compared to young ones (3-4 months). While there is a significant increase in the number of dark pinealocytes there is a decrease in the total number of pinealocytes in aged rats. This age-related loss of pinealocytes may explain the age-related functional decline of the pineal gland activity (e.g., the decrease of the nocturnal melatonin production). PMID- 7776178 TI - Circadian and ultradian variations of pituitary and pineal hormones in normal men: evidence for a link between melatonin, gonadotropin, and prolactin secretion. AB - The study was performed to investigate the physiological relationship between the pineal hormone melatonin and pituitary functions in normal men. Series of blood samples were obtained at 10-min intervals for 24-hr periods from 10 male volunteers (age 19-25 years). Samplings were repeated after 2 weeks and 3 months. Serum levels of melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone (T) were estimated by immunoassay methods (LH, PRL, every sample; melatonin, every 30 min; T, every 4 hrs; FSH once for each session). Diurnal characteristics of PRL and melatonin profiles were estimated by complex cosinor analysis, while short-term pulsatility of LH and PRL secretion was analyzed by the PULSAR algorithm. Data were correlated by linear regression analysis. The combined information of all three sampling sessions revealed significant negative correlations between the following parameters (N = 10): Amplitude (Ampl) melatonin and Ampl PRL: r = -0.727, P < 0.02; Ampl melatonin and maximal (Max) PRL values: r = -0.73, P < 0.02; Max melatonin and Max PRL: r = -0.725, P < 0.02; area under the curve (AUC) melatonin and Ampl PRL: r = -0.637, P < 0.05; AUC melatonin and Max PRL: r = -0.640; P < 0.05; duration (Dur) of melatonin synthesis and Ampl PRL: r = -0.685, P < 0.03; Dur melatonin and Max PRL: r = -0.676, P < 0.04; Dur melatonin and FSH levels: r = -0.663, P < 0.04; AUC melatonin and LH mean concentration: r = -0.732, P < 0.02; Max melatonin and LH mean concentration: r = -0.657, P < 0.04.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776179 TI - The enzymatic basis for the rat liver 6-hydroxymelatonin sulfotransferase activity. AB - Understanding 6-hydroxymelatonin (6HM) sulfation is deemed important to explaining normal and oncostatic actions of the pineal gland. Here we identify the enzymatic basis for this sulfation in rats. First, a quantitative assay was designed for measuring hepatic 6HM sulfotransferase (6HMST) activity. The assay was then used to identify a male dominant sexual dimorphism wherein liver from males contains double the 6HMST per g or per 100 g body weight seen in females. Examination of other rat tissues showed that most in vivo 6HM sulfation was likely to occur in liver. In addition, DEAE-Sephadex chromatography of liver cytosol indicated that 80-90% of the 6HMST activity in both sexes was due to an enzyme we named 6HMST II. A minor 6HM sulfotransferase (6HMST I) eluted from the columns prior to the main enzyme. 6HMST II, purified additionally, was shown to convert 6HM to a product that appeared to be 6HM sulfate (6-sulfa-toxymelatonin). The enzyme was inhibited by Na+, K+, Zn2+, and Cd2+. Its pH optimum was 7.80 +/- 0.30. Comparisons are made between 6HMST II, dopamine sulfotransferase II, and aryl sulfotransferase IV. PMID- 7776181 TI - Attractiveness of the underling: an automatic power --> sex association and its consequences for sexual harassment and aggression. AB - One characteristic of men who sexually harass is that they are not aware that their actions are inappropriate or a misuse of their power (L. F. Fitzgerald, 1993a). We investigated the existence and automaticity of a mental association between the concepts of power and sex, and its consequences for sexual harassment tendencies. Using a subliminal priming paradigm, Experiment 1 demonstrated an automatic link between power and sex, and only for men high in the likelihood to sexually harass or aggress. In Experiment 2, male participants were unobtrusively primed with either power-related or neutral stimuli. For men likely to sexually aggress, but not other participants, attraction ratings of a female confederate were significantly higher in the power priming than the neutral priming condition. PMID- 7776180 TI - When combining intrinsic motivations undermines interest: a test of activity engagement theory. AB - Three studies with elementary school children demonstrated that combining reading with coloring pictures can undermine children's later interest in reading, while also reducing their interest in coloring. Undermining is maximized when an activity is identified as secondary during the initial engagement, but other conditions must also be met as specified by activity engagement theory (Higgins & Trope, 1990): (a) the multiple input activities must be separately identified and considered simultaneously as alternatives, (b) the activity identified as primary during initial engagement must not be perceived as very attractive, and (c) the responses connected to an identified activity during the initial engagement must be activated subsequently. Conditions for enhancing interest in an activity are also considered. PMID- 7776182 TI - Fanning old flames: emotional and cognitive effects of suppressing thoughts of a past relationship. AB - Cognitive and electrodermal effects of suppressing thoughts of an old flame were examined in 2 experiments. Participants were asked to think aloud about an old flame--a past close relationship that either was or was not still desired--as their skin conductance level (SCL) was measured. Participants continued to think aloud as they were instructed either not to think about their old flame or to perform a comparison task. Participants were then asked to think about the old flame again. Participants who had suppressed thoughts of a no-longer-desired relationship were inclined to think aloud more about it afterward whereas those who suppressed thoughts of a still-desired relationship did not show such a rebound but evidenced increased SCL. PMID- 7776183 TI - Empathic accuracy in a clinically relevant setting. AB - This study addressed 3 questions regarding empathic accuracy in a clinically relevant setting. First, does the empathic accuracy of a perceiver improve with increased exposure to a target individual? Second, can empathic accuracy be enhanced by providing the perceiver with feedback about the target's actual thoughts and feelings? Third, are there stable individual differences in empathic accuracy that generalize across different targets? The results indicated that although absolute performance levels varied from 1 target to another, empathic accuracy generally improved with increased exposure to the target. In addition, feedback concerning the target's actual thoughts and feelings accelerated the rate at which the perceivers' empathic accuracy improved. Finally, cross-target consistency in responding (alpha = .86) revealed stable individual differences in the perceivers' empathic ability. Implications of these findings for clinical training and practice are discussed. PMID- 7776185 TI - Rigor, but not rigor mortis, in depression research. AB - With reference to the depression research methods review of H. Tennen, J.A. Hall, and G. Affleck (1995) and the earlier recommendations of P. C. Kendall, S. D. Hollon, A. T. Beck, C. L. Hammen, and R. E. Ingram (1987), the present discussion considers and then reaffirms selected methods. Discussion includes issues such as the use of analogue vs. clinical samples, single vs. multiple assessments, self report vs. structured diagnostic interviews, and the use of multiple gaiting and analyses of symptom clusters. PMID- 7776184 TI - Depression research methodologies in the Journal of Personality and Social Psychology: a review and critique. AB - Personality and social psychological studies of depression and depressive phenomena have become more methodologically sophisticated in recent years. In response to earlier problems in this literature, investigators have formulated sound suggestions for research designs. Studies of depression published in the Journal of Personality and Social Psychology (JPSP) between 1988 and 1993 were reviewed to evaluate how well these recommendations have been followed. Forty-one articles were examined for adherence to 3 suggestions appearing consistently in the literature: (a) multiple assessment periods, (b) multiple assessment methods, and (c) appropriate comparison groups. The studies published in JPSP have not adhered well to these standards. The authors recommend resetting minimum methodological criteria for studies of depression published in the premier journal in personality and social psychology. PMID- 7776186 TI - Activity and mood temperament as predictors of adolescent substance use: test of a self-regulation mediational model. AB - The authors tested a mediational model of temperament dimensions and substance use with a sample of 1,826 urban adolescents, M age 12.3 years. Five scales from the Revised Dimensions of Temperament Survey (DOTS-R) were administered together with measures of substance (tobacco, alcohol, marijuana) use and measures of related variables derived from a self-regulation model. Unique contributions to substance use were found for DOTS-R dimensions of high activity level (positively related) and positive mood (inversely related). High activity level and low positive mood were also related to lower levels of parental support. Analyses, including multiple regression and structural modeling, identified generalized self-control, maladaptive coping (anger and helplessness), novelty seeking, and affiliation with peer substance users as mediating the effect of temperament on substance use, with control for effects of parental support. Parental support was inversely related to substance use through several pathways. Implications for the theory of vulnerability are discussed. PMID- 7776187 TI - Attachment styles and repressive defensiveness: the accessibility and architecture of affective memories. AB - One hundred and twenty Israeli students were classified into secure, avoidant, and anxious-ambivalent attachment groups. They completed scales that tap the construct of repressive defensiveness and recalled early personal experiences of anger, anxiety, sadness, and happiness. Secure people reported moderate defensiveness and low anxiety and had easy access to negative memories without being overwhelmed by the spreading of the dominant emotional tone to nondominant emotions. Anxious-ambivalent people were unable to repress negative affects, reported high anxiety, had easy access to negative memories, and could not inhibit emotional spreading. Avoidant people reported high levels of defensiveness and anxiety and showed low accessibility to negative memories. The discussion emphasizes the parallel between a person's interaction with the social world and the makeup of his or her inner world. PMID- 7776188 TI - Resources, personal strivings, and subjective well-being: a nomothetic and idiographic approach. AB - The covariation of resources such as money, family support, social skills, and intelligence with subjective well-being (SWB) was assessed in 195 college students. Informant ratings provided an index of resources. Self-reports, daily experience sampling, and informant reports were used to measure SWB. The authors concluded that resources taken together are moderately strong predictors of SWB. This conclusion, however, was qualified by the fact that life satisfaction was more closely related to resources than was affective well-being and that social and personal resources were in general more strongly related to SWB than were material resources. The findings also supported the hypothesis that resources correlate more strongly with SWB when they are relevant to an individual's idiographic personal strivings. A tendency was found for people to choose personal strivings for which they have relevant resources, and the degree of congruence of individuals' goals with resources was predictive of SWB. PMID- 7776189 TI - Idiosyncratic trait definitions: implications for self-description and social judgment. AB - Descriptions of self (e.g., "I am dominant") may reflect not only a person's behavioral tendencies but also idiosyncratic definitions of the social concepts and categories being considered. Five studies revealed that participants who differed in their self-ratings along trait dimensions also tended to associate different behaviors and performances with those traits. For example, participants who described themselves as dominant tended to emphasize desirable over undesirable behaviors and characteristics in their definitions of the trait, whereas self-described nondominants highlighted the opposite. Participants' self ratings on dominance were also influenced by making positive or negative examples of dominant behavior salient to them. Moreover, when participants were induced to shift self-descriptions in self-serving ways, they tended to do so by revising their prototype of the trait in question. Discussion centers on the implications of these findings for the prediction of behavior and the interpretation of some social science results. PMID- 7776190 TI - Emotional conflict and well-being: relation to perceived availability, daily utilization, and observer reports of social support. AB - The link between emotional conflict and the perceived availability and use of social support was examined. One hundred and five undergraduate students completed measures of ambivalence over expressing emotion, repressive defensiveness, fear of intimacy, social support, and well-being. Self-reports, observer reports, and daily reports of social support during the previous month were collected. Both ambivalence and fear of intimacy were negatively related to self-report and daily measures of social support and to well-being. Repressive defensiveness was unrelated to the social support measures. Perceived social support mediated the relation between emotional conflict and well-being. Results suggest the presence of a negative bias toward the use of social resources by conflicted individuals. PMID- 7776191 TI - [Fatty acid metabolism in patients with idiopathic dilated cardiomyopathy: characteristics and prognostic implications]. AB - The characteristics of myocardial fatty acid metabolism in patients with idiopathic dilated cardiomyopathy (DCM) were investigated by myocardial imaging with beta-methyl-p-[123I]iodophenyl-pentadecanoic acid (BMIPP) in 16 patients with DCM, 8 patients with hypertensive heart failure (HHF), and 11 normal subjects. Rest myocardial imaging with BMIPP and 201Tl was performed on another day. The index of myocardial BMIPP uptake, or uptake ratio, was calculated from the percentage uptakes of BMIPP and 201Tl. The index of inhomogeneity of intramyocardial isotope distribution was calculated as the coefficient of variation of BMIPP and 201Tl. The uptake ratio was significantly lower in DCM and HHF patients than in normal subjects (p < 0.01). Uptake ratio correlated well with fractional shortening (r = 0.76, p < 0.01), and left ventricular ejection fraction (r = 0.58, p < 0.01). Although uptake ratio was not different between DCM and HHF patients, defects in BMIPP imaging appeared more frequently in DCM (69%) than in HHF (38%) patients. Furthermore, the extent of the defect in BMIPP imaging in DCM patients was larger than that in 201Tl imaging (p < 0.05), but in HHF patients the extent of the defects in both methods was similar. The coefficient of variation of BMIPP in DCM patients was greater than those in HHF patients and in normal subjects, but those of 201Tl were not different between the three groups. The coefficient of variation of BMIPP in DCM patients correlated well with serum norepinephrine level (r = 0.57, p < 0.01) and atrial natriuretic peptide (r = 0.77, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776192 TI - [Change in the treatment procedures for mitral valve disease]. AB - This study investigated the changes in treatment procedures for mitral stenosis (MS) and mitral regurgitation (MR) against the background of a decrease in the incidence of rheumatic valvular disease. The study included 3,955 patients with MS undergoing closed mitral commissurotomy (CMC), open mitral commissurotomy (OMC), mitral valve replacement (MVR), or percutaneous transvenous mitral commissurotomy (PTMC) between 1952 and 1991, and 478 patients with MR undergoing MVR or mitral valvuloplasty in the Heart Institute of Japan, Tokyo Women's Medical College. The number of patients with MS undergoing surgical or catheter interventions has decreased and is now about 80 per year, a half of that experienced in the 1960s. CMC and OMC have been replaced by PTMC since the 1990s. The most popular treatment procedure is now MVR. The number of patients with MR undergoing surgery has increased to about 30 per year. Eighty percent of operations for MR are MVR and the others are mitral valvoplasty. Survey of the etiology of MR shows decreased rheumatic disease and increased degenerative disease. The incidence of MR due to ischemic heart disease and hypertrophic obstructive cardiomyopathy has slightly increased. PMID- 7776193 TI - [Mitral valve repair for infectious endocarditis]. AB - Fourteen patients with mitral regurgitation resulting from infectious endocarditis underwent mitral valve repair between December 1988 and July 1994. There were nine males and five females aged from 14 to 70 years (mean 40.2 +/- 19.7 years). Three patients had active endocarditis. Time between the onset of endocarditis symptoms and surgery ranged from 1 to 24 months (mean 8.3 months). Bacterial findings were Streptococcus in eight patients, Staphylococcus in one, and unknown in five. All macroscopically infected tissue was excised in patients with active endocarditis. Carpentier's reconstructive techniques were mainly used. There were no hospital deaths. Mean follow-up was 29 months and complete. Thirteen patients were in New York Heart Association functional class I and one in class II. There were no late deaths, reoperations, recurrent endocarditis, thromboembolic events, or other valve-related morbidity. We conclude that mitral valve repair is an attractive procedure in patients with mitral regurgitation resulting from infectious endocarditis. PMID- 7776195 TI - [The influence of electrical time interval indices and aging on the left atrial systolic time intervals]. AB - The influence of aging and heart rate on left ventricular systolic time intervals is well known, but the effects on left atrial systolic time intervals, a new index of left atrial function, remain unknown. The influence of aging and heart rate on left atrial systolic time intervals was investigated in 43 normal subjects (13-72 years of age) by Doppler echocardiography. Atrial pre-ejection period, atrial ejection time, and corrected atrial pre-ejection period were obtained by transmitral Doppler echocardiography. Simple regression analysis showed atrial pre-ejection period significantly correlated with P wave duration (PP; r = 0.78), and PR interval (PR; r = 0.60), but not with RR interval (RR). However, multiple regression analysis showed atrial pre-ejection period significantly correlated only with PP. Simple regression analysis found atrial ejection time significantly correlated with PP (r = 0.38), and PR (r = 0.39), but not with RR. However, multiple regression analysis found atrial ejection time did not correlate with any factor significantly. Aging was significantly correlated with corrected atrial pre-ejection period (r = -0.37), but not with corrected atrial ejection time and atrial pre-ejection period. Atrial ejection time significantly correlated with corrected atrial pre-ejection period (r = -0.37), but not with atrial pre-ejection period. Corrected atrial pre-ejection period is a clinically useful index of left atrial systolic function. PMID- 7776194 TI - [Clinical evaluation of 123I-metaiodobenzylguanidine myocardial scintigram in patients with valvular heart disease]. AB - Myocardial sympathetic nerve function can be evaluated by 123I metaiodobenzylguanidine (MIBG) scintigraphy. Congestive heart failure is closely related to myocardial sympathetic nerve function. This study evaluated the severity of congestive heart failure in 30 patients with valvular heart disease [aortic regurgitation (AR): n = 20, mean age = 70 +/- 13 years; mitral regurgitation (MR): n = 10, mean age = 61 +/- 18 years], who had chronic heart failure by MIBG myocardial scintigraphy. Single photon emission computed tomography (SPECT) and anterior planar myocardial images were obtained 15 minutes (initial images) and 4 hours (delayed images) after injection of MIBG (111MBq). Defect score was determined by the delayed SPECT images visually as a semi quantitative index. Myocardial MIBG uptake was quantified by the heart to upper mediastinum uptake ratio on the delayed anterior planar images (H/M) and mean cardiac MIBG washout rate during 4 hours was calculated from the bull's eye display data (clearance). These indices were compared with the NYHA class and echocardiographic findings of the patients. MIBG regional defect in the delayed image was most frequently seen in the inferoposterior wall, and defect score and clearance were significantly higher and the H/M ratio was significantly lower in NYHA class III patients than in class II patients. In patients with AR, clearance significantly correlated with left ventricular end-systolic dimension. In patients with MR, both the H/M ratio and clearance significantly correlated with left atrial dimension. Defect score, H/M, and clearance were closely related to the severity of AR and MR. These results indicate that MIBG scan can be used to assess the severity of valvular heart disease. PMID- 7776196 TI - [Right-sided infectious endocarditis due to methicillin-resistant Staphylococcus aureus resulting in ruptured abscess of the ventricular septum and sinus of Valsalva]. AB - A 24-year-old woman presented with right-sided infectious endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA). This is the first report of right-sided infectious endocarditis caused by MRSA in Japan. The patient was admitted to the Jichi Medical School Hospital because of fever of unknown origin and disturbance of consciousness. Several months before, she had discontinued treatment for hyperthyroidism. Antibiotics effective against MRSA, vancomycin and flomoxef, were given intravenously, but a new heart murmur was detected. Echocardiographic study revealed vegetations attached to the tricuspid valve and abscess formation on the ventricular septum. The vancomycin dosage was increased and arbekacin sulfate was also given from the sixth hospital day. However, these antibiotics had very little effect and the abscess rapidly increased in size. Color flow mapping finally demonstrated intracardiac shunt flow through the ruptured abscess of the ventricular septum and sinus of Valsalva. She died suddenly, probably from heart failure. The prognosis of infectious endocarditis due to MRSA is poor and drug therapy often fails. Thus, surgery should be considered in the early stage. PMID- 7776197 TI - [Instrumental problems with the apex cardiogram]. PMID- 7776198 TI - Acronyms of clinical trials in cardiology--1995. PMID- 7776200 TI - "I did so!" But can you prove it? Avoiding claims through documentation. AB - The author explains the need to document medical records to provide protection in litigation and to enhance medical care. Practical tips to make documentation easier and more efficient are given. PMID- 7776199 TI - Podiatric malpractice litigation. What to do and what to expect. AB - Many podiatric physicians will never be sued during their careers, but if a suit happens, it can be one of the most stressful times in their lives. After contacting the insurance carrier, the podiatric physician must then wait as the case develops through the legal system. The deposition is when the podiatric physician will be asked questions about the case. It is important to remember to carefully answer the questions asked. Once in the trial stage, the appearance and testimony of the podiatric physician will be important in the jury's eyes. If a decision is not in your favor, you may be able to appeal the case to a higher court. Some cases may not go to trial as they could be settled or arbitrated along the way. By listening to your attorney and following the attorney's advice and recommendations, the legal process will be easier to manage and understand. PMID- 7776201 TI - Informed consent. Legal requirements for surgical procedures. PMID- 7776202 TI - Tips for testifying. AB - The author offers practical suggestions for the witness to help improve effectiveness without compromising truthfulness when testifying in depositions and trial. The guidelines are designed to reduce the podiatrist's apprehension when venturing into the legal arena and to serve as resource material. PMID- 7776203 TI - Problems with procedures. AB - The author evaluated over 2,000 nationwide claims in 14 years of podiatric malpractice suits. Surgical results are reviewed along with primary areas that generate claims. Suggestions are given on the impending claims and recommendations for abatement. PMID- 7776204 TI - Performing a workers' compensation medicolegal evaluation. AB - The purpose of this article is to familiarize the reader with the elements and parameters of a worker's compensation medicolegal evaluation. Physicians play a critical role in the determination of whether an alleged injury warrants compensation and vocational training. The author provides information that will assist the physician who is called on to make such a judgment. PMID- 7776206 TI - Fatal pontine hemorrhage after podiatric surgery. A case report. AB - The authors present a case of massive fatal pontine hemorrhage as a complication of hypertension in a patient treated for an infected diabetic ulcer. The podiatric physician must be aware of the risks associated with concomitant medical problems such as hypertension and ensure that proper therapeutic measures are taken to avoid the potential for catastrophic complications. PMID- 7776205 TI - Scope of practice in podiatric sports medicine. AB - The author discusses the issue of scope of practice in podiatric sports medicine and cases involving this area of practice, as well as the attendant ramifications. By gaining insight into this tissue, it is hoped the importance of practicing within the specific state scope of practice laws will be recognized. PMID- 7776207 TI - Scintigraphic detection of sequential symmetrical metatarsal stress fractures. AB - A patient with complaints of right foot pain and previous normal radiographs had an abnormal three-phase bone scan consistent with a second metatarsal stress fracture. Subsequent radiographs confirmed this diagnosis. Two months later, the patient developed pain in his left foot, and again initial radiographs were noncontributory. A later bone scan revealed a left second metatarsal stress fracture. The results in this case reemphasize the value of bone scintigraphy in patients with foot pain and no bone abnormalities on plain radiographs. PMID- 7776208 TI - Fracture of the fifth digit. An atypical presentation. AB - Digital fractures are a common injury in the forefoot. Most fractures, however, do not present relatively free of pain. When they present without pain or with few symptoms, they may be overlooked or misdiagnosed. The following is a case presentation of a patient who presented to Franklin Delano Roosevelt Hospital after trauma to the right fifth toe. The case was atypical in that the patient was asymptomatic despite the recent injury. Rapid conservative intervention by the patient at home, coupled with sensory neuropathy secondary to diabetes, can alter the clinical presentation as witnessed in this case. An appropriate history and physical examination combined with radiographs were essential to an otherwise ordinary clinical presentation. PMID- 7776209 TI - Bullosis diabeticorum. AB - The authors present a case of bullous dermatosis in a diabetic patient. The lesions were drained and deroofed, and at 1-year follow-up, the patient related no problems. Proper diagnosis and treatment of these lesions will avoid infection and ulceration. PMID- 7776210 TI - Total contact casting. AB - The treatment of diabetic foot ulcerations has been a difficult task for podiatrists. Numerous methods and materials have been used in an attempt to alleviate this frustrating and complex treatment dilemma. However, there is one treatment method that has been used successfully for decades on plantar ulcerations of the neuropathic foot. Total contact casting has been an easily applicable and effective treatment modality for neuropathic ulcerations of the diabetic foot. PMID- 7776211 TI - Patient education for diabetic patients. An integral part of quality health care. AB - The diabetic patient is at high risk for developing long-term medical complications including serious foot problems with potential loss of limb. With today's growing awareness of the importance of curtailing overall health care costs, the importance of comprehensive diabetic patient education programs is academic. It is demonstrated that a multidisciplinary approach to diabetic care management, with foot care assessment encompassing early preventive measures, can serve as a model for other Veterans Affairs Medical Centers to follow. Foot screenings can individualize specific foot problems and provide an understanding of risk factors to prevent complications. Patients with diabetes or peripheral vascular disease and, especially those individuals at risk of foot ulceration, are referred to the appropriate clinic for ongoing management to prevent amputation. Patient education is considered most effective when it is encouraged throughout a diabetic patient's medical care, and it becomes a part of lifestyle habits. PMID- 7776212 TI - Comparison of rearfoot motion in overground versus treadmill walking. AB - The purpose of this study was to determine whether walking on a treadmill is a valid simulator of overground walking with respect to rearfoot motion. The tibial, calcaneal, and rearfoot motions of 10 subjects (2 males, 8 females) were videotaped while they walked on a treadmill and overground. The results of a series of t-tests showed that there was no statistically significant difference between the two conditions on any of the variables measured. PMID- 7776213 TI - Shortening Z-osteotomy for the proximal phalanx of the hallux using axial guides. AB - The shortening Z-osteotomy of the proximal phalanx of the hallux has been presented as an alternative to the Regnauld enclavement procedure for patients with the appropriate indications. In addition to sharing the same positive characteristics as the Regnauld procedure, the Z-osteotomy has technical and physiologic advantages. The advantages of the Z-osteotomy over the Regnauld include maintenance of the intrinsic attachments at the base of the proximal phalanx, less risk of avascular necrosis, less technical difficulty, and absence of complications associated with an autogenous bone graft. Also, it does not affect the sesamoid apparatus. Research and extended follow-up studies will continue at Lakewood Regional Medical Center. In the last year, one author has completed approximately 13 of these procedures. The postoperative results have been encouraging and successful with one exception. In one case, the increase of the hallux interphalangeal angle was probably caused by excessive tightening of the distal screw compared with the proximal screw. PMID- 7776214 TI - Conservative podiatric medicine and disability in elderly people. AB - A survey was conducted of 248 noninstitutionalized people aged 75 years and older, residing in a designated geographical area. The effect of dependency and physical disability on the receipt of conservative podiatric medicine was examined, and, in addition, the prevalence of medical and podiatric conditions was determined. PMID- 7776215 TI - Chromoblastomycosis. A fungal infection primarily observed in the lower extremity. AB - Chromoblastomycosis is a cutaneous-subcutaneous fungal infection that is being seen more frequently in patients living in the US. The disease normally occurs in patients living in tropical and subtropical regions, but as the number of immigrants into the US increases, podiatrists must be able to recognize the manifestations of chromoblastomycosis. The most common sight involved is the lower extremity where it easily can be confused with other diseases such as tertiary syphilis, phaeohyphomycosis, and cutaneous tuberculosis, among others. Small lesions should be excised, while antifungal drugs, such as itraconazole, should be used when more tissue is involved. PMID- 7776216 TI - Elephantiasis nostras verrucosa. A case report. PMID- 7776217 TI - Chronic elephantiasis. A case report. AB - The authors presented a rare case study of a patient with chronic elephantiasis involving the lower extremities. The patient had contracted lymphatic filariasis while serving in the armed forces during World War II. The patient was followed regularly for local wound care by the Veterans Affairs podiatry department. However, he died from congestive heart failure and pneumonia in May of 1993. PMID- 7776218 TI - Verrucous carcinoma with a dorsal sinus tract. AB - A verrucous carcinoma of the right foot was presented. A unique finding, a dorsal sinus tract at the base of the fourth toe, was found on examination, which communicated with the tumor. Other reports of a sinus tract extending to the dorsal surface of the foot could not be found in the literature. PMID- 7776219 TI - Presentation of an intermetatarsal ganglion. AB - Ganglia have occurred in almost all areas of the foot, but most often associated with capsular or tendinous structures. They are fluid-filled masses which often present themselves radiographically as increases in soft tissue density. Ganglia exhibit high intensity magnetic resonance imaging and must be clinically and pathologically differentiated from other masses, such as, but not limited to, neuromas, granulomas, and neurilemomas. The authors present a rare occurrence of an intermetatarsal ganglionic cyst associated with the third dorsal interossei muscle, which was large enough to cause bony deformation of the adjacent metatarsals. It is unusual for ganglia to cause alterations in bone unless they are intraosseus in nature. Bone deformation and invasion are usually associated with aggressive tumors. PMID- 7776220 TI - Articular cartilage. Part I. The normal joint. AB - Articular hyaline cartilage is of interest to both the clinician and the basic scientist because of its unique physical and chemical properties which are a consequence of its biochemical composition. Although it is a tissue which is hypocellular, avascular, and also lacks nerves and lymphatics, it is active in synthesis and degradation. Articular cartilage responds to the forces to which it is subjected and, in this way, maintains its integrity as long as those forces do not exceed the tissue's capacity for repair or permanently change the biologic response of the cells. PMID- 7776221 TI - Articular cartilage. Part II. The osteoarthritic joint. AB - Articular hyaline cartilage, though a metabolically active tissue, has limited capacity for repair. Though the integrity of the cartilage is dependent upon a certain level of force placed upon it, excessive force leads to damage. It is when the breakdown of the cartilage exceeds the capacity of the cartilage for repair that osteoarthritis results. At present, pharmacologic treatment of osteoarthritis is focused toward the control of pain and stiffness. This treatment, however, masks the symptoms of the disease and effectively allows the patient to do further damage to the joint. PMID- 7776222 TI - Nonskid socks. AB - For children with normal anatomy, nonskid socks may be safe for indoor wear. However, they lack some protection capacity, and are not biomechanically helpful. Little scientific data exist to guide physicians on what children should wear on their feet. Dogma and prejudice may taint the advice physicians give. Perhaps this type of project will spur further investigation. PMID- 7776223 TI - Reversal of somatic neuropathy in a diabetic patient treated with pancreas-kidney transplantation. PMID- 7776224 TI - Who treats feet? PMID- 7776225 TI - A sustained inward current activated at the diastolic potential range in rabbit sino-atrial node cells. AB - 1. After blocking both the hyperpolarization-activated current and the membrane K+ conductance, depolarizations from -80 mV to between -70 and -50 mV induced a sustained current in sino-atrial node cells. We have tentatively designated this current Ist. 2. Ist was blocked by both organic and inorganic Ca2+ channel blockers, but was insensitive to tetrodotoxin (30 microM). Isoprenaline increased Ist. 3. The peak of Ist (at about -50 mV) was increased to 149 +/- 13% (n = 8, P < 0.01) by lowering the external Ca2+ concentration ([Ca2+]o) from 1.8 to 0.1 mM, in contrast to the marked depression of the L-type Ca2+ current. In 0.1 mM [Ca2+]o solution, the nicardipine-sensitive current-voltage relation showed the peak amplitude at about -50 mV and a reversal potential of +37.4 +/- 4.4 mV (n = 5). The isoprenaline-sensitive component also showed a reversal potential of about +30 mV. 4. Reducing [Na+]o from 140 to 70 mM in 0.1 mM [Ca2+]o decreased Ist to 53 +/- 5% (n = 7, P < 0.01). Increasing [Ca2+]o or [Mg2+]o decreased the amplitude of Ist. The half-maximum concentration of Mg2+ inhibition was 2.2 mM. 5. At 1.8 mM [Ca2+]o, Ist was inactivated by clamping for 5s at -10 mV, and gradually recovered after repolarization to -80 mV with a half-time of 1.36 +/- 0.4 s (n = 6). 6. The transitional sino-atrial node cell had minimal amplitude of Ist. 7. These characteristics of Ist are qualitatively comparable to those of the monovalent cation conductance of the L-type Ca2+ channel induced by depleting external divalent cations to the micromolar range. We conclude that Ist is generated by a novel subtype of L-type Ca2+ channel. PMID- 7776226 TI - Expression and distribution of sodium channels in short- and long-term denervated rodent skeletal muscles. AB - 1. Loose-patch voltage-clamp recordings were made from rat and mouse skeletal muscle fibres denervated for up to 6 weeks. Innervated muscles possessed a Na+ current density of 107 +/- 3.3 mA cm-2 in endplate membrane, and 6.3 +/- 0.6 mA cm-2 in extrajunctional membrane. This high concentration of Na+ channels at the endplate was gradually reduced following denervation. After 6 weeks of denervation, the endplate Na+ channel concentration was reduced by 40-50%, and the density of Na+ channels in extrajunctional membrane was increased by about 30%. 2. The tetrodotoxin (TTX)-resistant form of the Na+ channel appeared after 3 days of denervation and comprised approximately 43% of the endplate Na+ channels 5-6 days after denervation. Subsequently, TTX-resistant Na+ channels were reduced in density to approximately 25% of the postjunctional Na+ channels and remained at this level up to 6 weeks after denervation. 3. RNase protection analysis showed that mRNA encoding the TTX-resistant Na+ channel was virtually absent in innervated muscle, rose > 50-fold after 3 days of denervation, then decreased by 95% 6 weeks after denervation. The density of TTX-resistant Na+ channels correlated qualitatively with changes in mRNA levels. 4. These results suggest that the density of Na+ channels at neuromuscular junctions is maintained by two mechanisms, one influenced by the nerve terminal and the other independent of innervation. PMID- 7776228 TI - Effects of testosterone on synaptic efficacy at neuromuscular junctions in a sexually dimorphic muscle of male frogs. AB - 1. The effects of testosterone on synaptic efficacy were studied in the flexor carpi radialis, a sexually dimorphic forelimb muscle involved in frog clasping behaviour. Male Xenopus laevis frogs were castrated and then given either testosterone-filled implants (CT frogs) or empty implants (C frogs) for 2, 8 or 16 weeks. 2. Intracellular recordings were made from fibres in the shoulder region and in a region midway between the elbow and wrist. These regions are mainly innervated by spinal nerve 2 (SN2) and spinal nerve 3 (SN3), respectively. 3. In CT muscles, the percentage of fibres that failed to generate an action potential in response to a single nerve stimulus was greater than in C muscles. The percentage of such fibres was greater among SN2 fibres than among SN3 fibres. 4. The input resistance and membrane time constant were lower in CT muscles than in C muscles for SN2 fibres but not for SN3 fibres. The action potential threshold was lower in CT muscles than in C muscles. In SN2 fibres, the action potential threshold was higher than in SN3 fibres. 5. Quantal content with 1 Hz nerve stimulation and miniature endplate potential (MEPP) frequency did not differ between CT and C junctions. However, both parameters were lower at SN2 junctions than at SN3 junctions. The amplitude of MEPPs was lower in CT muscles than in C muscles only for SN2 junctions. 6. Facilitation of transmitter release with 70 or 10 Hz nerve stimulation was greater at CT junctions than at C junctions. Also, SN2 junctions showed greater facilitation than SN3 junctions. 7. We hypothesize that the more androgen-sensitive SN2 junctions, which have lower quantal content and greater facilitation, belong to motor units that are tonically active, fatigue resistant, and contract more slowly. The less androgen sensitive SN3 junctions, which have higher quantal content and less facilitation, may belong to motor units that are phasically active, fatigable and contract more rapidly. Testosterone enhances these differences such that flexor carpi radialis junctions are better adapted to the functional demands of clasping. PMID- 7776227 TI - Length dependence of Ca2+ sensitivity of tension in mouse cardiac myocytes expressing skeletal troponin C. AB - 1. Beat-to-beat performance of myocardium is highly dependent on sarcomere length. The physiological basis for this effect is not well understood but presumably includes alterations in the extent of overlap between thick and thin filaments. Sarcomere length dependence of activation also appears to be involved since length-tension relationships in cardiac muscle are usually steeper than those in skeletal muscle. 2. An explanation recently proposed to account for the difference between length-tension relationships is that the cardiac isoform of troponin C (cTnC) has intrinsic properties that confer greater length-dependent changes in the Ca2+ sensitivity of tension than does skeletal troponin C (sTnC), presumably due to greater length-dependent changes in the Ca(2+)-binding affinity of cTnC. To test this hypothesis, transgenic mice were developed in which fast sTnC was expressed ectopically in the heart. This allowed a comparison of the length dependence of the Ca2+ sensitivity of tension between myocytes having thin filaments that contained either endogenous cTnC or primarily sTnC. 3. In myocytes from both transgenic and normal mice, the Ca2+ sensitivity of tension increased similarly when mean sarcomere length was increased from approximately 1.83 to 2.23 microns. In both cases, the mid-point (pCa50) of the tension-pCa (i.e. log[Ca2+]) relationship shifted 0.12 +/- 0.01 pCa units (mean +/- S.E.M.) in the direction of lower Ca2+. 4. We conclude that the Ca2+ sensitivity of tension in myocytes changes as a function of sarcomere length but is independent of the isoform of troponin C present in the thin filaments. PMID- 7776230 TI - Cellular basis of temporal synaptic signalling: an in vitro electrophysiological study in rat auditory thalamus. AB - 1. The cellular mechanisms underlying temporal synaptic signalling of tectothalamic pathways were investigated in rat medial geniculate body (MGB) maintained in vitro. Stimulation of the brachium of the inferior colliculus elicited either a short latency, single- (or dual-) spike or a long latency (10 80 ms) burst in MGB neurones. The delayed burst response was found in most non lemniscal or caudodorsal MGB (MGd) neurones, whereas single-spike units were mainly seen in the lemniscal ventral MGB (MGv). Population latency analysis revealed that the overall relay time of tectothalamic transmission is approximately 50 ms, with at least two excitation peaks occurring around 8 and 15 ms, respectively. 2. Intracellular recordings showed that the delayed burst responses in MGd neurones were mediated by an EPSP-triggered low threshold spike (LTS). Small variations in either the membrane voltage or in EPSP amplitude induced significant shifts of LTS latency. 3. Compared with MGv cells, MGd neurones exhibited a more negative resting membrane potential and a prolonged EPSP; they lacked an apparent hyperpolarization-activated inward rectifier (Ih). These factors seem to lead collectively to a dominant occurrence of long latency burst response in the MGd. In the majority of single-spiking MGv cells that expressed a clear Ih, application of Cs+ consistently hyperpolarized the cell, which transformed a single-spike synaptic response into an EPSP-LTS burst or a subthreshold EPSP. 4. Taken together, these data suggest that the monosynaptic tectothalamic pathways are capable of introducing a ventrodorsal gradient in auditory response time. This synaptic activity pattern is probably dominantly regulated by a set of membrane conductances expressed endogenously in thalamocortical neurones. PMID- 7776229 TI - Effects of creatine phosphate and inorganic phosphate on the sarcoplasmic reticulum of saponin-treated rat heart. AB - 1. Ventricular trabeculae from rat heart were permeabilized by treatment with saponin. In the presence of 150 nM Ca2+, application of 20 mM caffeine released Ca2+ from the sarcoplasmic reticulum (SR), resulting in a transient contracture. Ca2+ released from the SR was detected using fura-2 fluorescence. The amplitudes of the caffeine-induced Ca2+ transients were used to assess SR Ca2+ content. 2. In the absence of creatine phosphate (CP), introduction of 5-30 mM inorganic phosphate (Pi) caused a net release of Ca2+ from the SR. Subsequent caffeine induced Ca2+ and tension transients were smaller in the presence of Pi. Under these conditions, 30 mM Pi decreased the caffeine-induced Ca2+ transients by 45 +/- 3.1% (mean +/- S.D., n = 14). On removal of Pi, the [Ca2+] transiently decreased and the caffeine-induced Ca2+ transients returned to control levels over 4-6 min. 3. In the presence of CP (5-15 mM), the Ca2+ transients were unaffected by the introduction of Pi (5-30 mM) or slightly increased in amplitude. Pi (30 mM) significantly increased the caffeine-induced Ca2+ transients by 7 +/- 8.8% (mean +/- S.D., n = 19, P < 0.05) in the presence of 15 mM CP. The release of Ca2+ on addition of Pi and decrease in [Ca2+] on Pi withdrawal was less pronounced or absent completely in the presence of CP. The inhibitory effects of Pi on caffeine-induced Ca2+ release became apparent as the [CP] was decreased from 5 to 0 mM. 4. In the presence of the creatine phosphokinase inhibitor dinitro-fluorobenzene (DNFB) the effects of Pi (in the presence of CP) were qualitatively similar to the results obtained in the absence of CP, although the decrease in caffeine-induced Ca2+ release was less pronounced. 5. These results suggest that the rise in [Pi]i during ischaemia or anoxia will have little effect on the regulation of Ca2+ by the SR while the [CP]i remains above 5 mM. However, as the [CP] decreases below 5 mM, the accumulation of Pi within the cytosol will progressively reduce the SR Ca2+ content. CP may act in conjunction with endogenous creatine phosphokinase to modify the response of the SR to Pi, and possible mechanisms are considered. PMID- 7776231 TI - Synaptic integration in layer IV of the ferret striate cortex. AB - 1. Whole-cell patch recording were made with dye-filled electrodes from layer IV in slices of the ferret striate cortex. Projections from the thalamus and layer VI provide most of the extralaminar input to layer IV. Interactions between these two pathways are thought to play a role in the generation of suppressive non linearities such as end-inhibition. Thus, synaptic responses evoked by stimulating each pathway individually were compared with those produced by activating both projections together. 2. Spiny stellate cells are the majority population in layer IV and were the most frequently patched neurons (n = 23); all fired adapting trains of large, fast action potentials. About half of those tested (n = 13) were progressively inhibited by strengthening the stimulus to layer VI, while the rest became more excited. For the former, the response evoked by stimulating both pathways in coincidence was often more hyperpolarizing than would have been predicted by summing the responses to either projection alone (n = 4). Hence, the inputs from the thalamus and layer VI are integrated by circuits that can produce strong and non-linear inhibition. 3. Recordings from various basket cells, which are inhibitory, have provided a first view of the suppressive circuits in layer IV (n = 5). Two cells were excited by stimulation of both pathways. The remaining three cells were mainly excited by activation of thalamic afferents but were largely inhibited by stimulation of layer VI. Thus, inhibition seen at the level of the spiny stellate cells could result from two mechanisms operating via presynaptic smooth cells: convergent excitation provided by both ascending pathways on the one hand, and a push-pull relationship between pathways on the other. PMID- 7776232 TI - Regulation of granule size in human and horse eosinophils by number of fusion events among unit granules. AB - 1. We have investigated the granule size distributions in human and horse eosinophils by time-resolved patch-clamp capacitance measurements. 2. During exocytosis of single granules the electrical capacitance of the plasma membrane increases in discrete steps. The steps in horse cells are about six times larger than those in human cells in accordance with the difference in granule size. 3. In both species a multimodal capacitance step size distribution is observed with a first peak at 6-7 fF corresponding to granules with a diameter of about 450-500 nm and a surface area of about 0.7 microns2, which we call the unit granule. The other peaks in the distributions correspond to multiples of the surface area of these units. 4. These results show that the larger granules are formed by fusion of several unit granules and the final size of mature granules is determined by the number of units allowed to fuse with each other. Whereas in human eosinophils most granules consist of one or two units, most granules of horse eosinophils are formed by fusion of seven to fifteen units. 5. The intracellular fusion events associated with vesicular traffic are believed to occur constitutively. In contrast, our results indicate that a cellular mechanism exists which regulates the size of the mature granules by determining the number of units allowed to fuse with each other. In view of our recent report that granule-granule fusion can be activated by GTP gamma S, this regulation may possibly involve GTP-binding proteins. PMID- 7776233 TI - Central inhibitory effects of muscimol and bicuculline on the milk ejection reflex in the anaesthetized rat. AB - 1. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central administration of a GABAA receptor agonist (muscimol) and antagonist (bicuculline) on the milk ejection reflex in the urethane-anaesthetized rat. 2. Intracerebroventricular (i.c.v.) injection of both muscimol (n = 17), at doses of 5, 10 and 20 ng, and bicuculline (n = 15), at doses of 0.01, 0.1 and 0.3 microgram, inhibited the milk ejection reflex in a dose-dependent manner. The bicuculline-induced inhibition was accompanied by desynchronization of the electroencephalogram and, at the highest dose, by alteration in the sensitivity of the mammary gland to oxytocin. No significant effect on the milk ejection reflex was seen with i.c.v. isotonic saline (n = 5). 3. Injection of 20 (n = 5) or 40 ng (n = 2) muscimol or 0.1 microgram bicuculline (n = 5) i.c.v. did not significantly alter the rise in intramammary pressure evoked by electrical stimulation of the neurohypophysis. 4. Bilateral 400 nl microinfusions directly into the supraoptic nuclei of either muscimol (20-100 ng microliter(-1); n = 10) or bicuculline (0.15 micrograms microliter(-1); n = 5) [corrected] resulted in an inhibition of the milk ejection reflex, which was not accompanied by desynchronization of the electroencephalogram. 5. The effects of i.c.v. injections of muscimol (15 and 20 ng) and bicuculline (0.01, 0.12 and 0.3 microgram) on the electrical activity of twenty-seven antidromically identified supraoptic magnocellular neurones were examined. Both compounds resulted in an inhibition of the background firing of oxytocinergic and vasopressinergic cells, and delayed the occurrence of high frequency bursts in oxytocin neurones. In five supraoptic neurones, bicuculline induced a transient activation before inhibition. 6. The powerful inhibitory action on the milk ejection reflex of both muscimol and bicuculline provides evidence for the importance of GABA neurones in maintaining the functional integrity of the mechanisms which allow the intermittent and pulsatile release of oxytocin during suckling. PMID- 7776235 TI - Inhibitory effect of sympathetic stimulation on activities of masseter muscle spindles and the jaw jerk reflex in rats. AB - 1. To evaluate sympathetic effects on jaw muscles, the discharges of masseter muscle spindle afferents, jaw muscle electromyographic (EMG) activities and blood flow changes were compared in anaesthetized decerebrate rats before and during electrical stimulation of the cervical sympathetic trunk. 2. To eliminate the possibility of efferent control from the trigeminal motoneurones, muscle spindle activity was recorded from the cut peripheral end of the masseter nerve. The absence of a sympathetic component in the masseter nerve was confirmed by the horseradish peroxidase method. 3. Electrical stimulation of the sympathetic nerve at frequencies within the physiological range reduced muscle spindle afferent discharges evoked by passive jaw opening. 4. Sympathetic stimulation also reduced the EMG activity evoked by the jaw jerk reflex, which may reflect a sympathetic effect on spindle afferents. After cessation of stimulation, a transient increase in EMG activity was observed, which may be due to efferent supply from the trigeminal motoneurones. During rhythmical jaw movements, no sympathetic effect on EMG activity was detected. 5. The above sympathetic effect on muscle spindle afferents and EMG activity was independent of blood flow changes. PMID- 7776234 TI - Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway. AB - 1. The effects of nitrosocysteine (cys-NO), L-N omega-nitroarginine (L-NNA) and L N omega-nitro-L-arginine methylester (L-NAME), oxyhaemoglobin and Methylene Blue were observed on the resting membrane potential, muscle tone and excitatory junction potentials (EJPs) of cat tracheal smooth muscle tissue. 2. Cys-NO (10( 9) to 10(-6) M) showed no effect on the resting membrane potential of smooth muscle cells of the cat trachea but it dose-dependently relaxed the tracheal tissue in the presence of 5-HT, atropine and guanethidine. 3. Electrical field stimulation (EFS) applied during contraction evoked by 5-HT in the presence of atropine and guanethidine evoked non-adrenergic, non-cholinergic (NANC) muscle relaxation. L-NNA (10(-4) M) and L-NAME (10(-4) M) completely suppressed the relaxation when single or short repetitive stimuli were applied, but suppression was incomplete with repetitive stimuli of 4 ms pulse duration applied at 20 Hz. A substantial part of the L-NNA- or L-NAME-insensitive relaxation was abolished by tetrodotoxin. 4. Cys-NO dose-dependently suppressed the EJPs without changing the resting membrane potential, and L-NNA, L-NAME, Methylene Blue and oxyhaemoglobin enhanced the amplitude of the EJP to 1.2-1.5 times the control value. 5. EJPs showed some summation when repetitive field stimulation was applied at 20 Hz. L NNA or L-NAME enhanced the summation, and the mean slopes were increased from 0.61 +/- 0.22 to 2.0 +/- 0.3, or 1.9 +/- 0.2 mV per stimulus. Vasoactive intestinal polypeptide (VIP) antiserum and VIP antagonists further enhanced the summation in the presence of L-NNA. 6. These results indicate that NANC relaxation can be classified into two different components according to the threshold for activation, and nitric oxide is involved in one. The present results also suggest that endogenous or exogenous nitric oxide has a prejunctional action in inhibiting excitatory neuroeffector transmission in addition to a direct action on the smooth muscle cells, presumably by suppressing transmitter release from the vagus nerve. PMID- 7776236 TI - Responses of human masseter motor units to stretch. AB - 1. The reflex responses to stretch were studied in single motor units and the surface electromyogram in human masseter. 2. Controlled stretches of the isometrically contracting jaw-closing muscles evoked short-latency (10-15 ms) and long-latency (35-70 ms) excitatory reflex responses in the masseter surface electromyogram. 3. The majority (65%) of tonically active masseter motor units were excited in both short- and long-latency phases of the reflex. The timing of the stimulus determined whether the unit discharged in the short- or long-latency phase. If a non-tonically active motor unit was recruited by the stimulus, it invariably discharged in the long-latency phase. 4. Although short-latency responses were strongly time-locked to the stimulus, there was very little shortening of interspike intervals (ISIs) in this phase of the reflex. The shortening of ISIs was more prominent and prolonged during the long-latency phase, which explains why this phase produces most of the reflex force changes following the stretch. 5. Within pairs of concurrently active motor units there was a tenfold range in the size of the short-latency response to the same stretch. 6. A substantial proportion (35%) of the twenty-two masseter motor units tested had no statistically significant short-latency reflex response. 7. In contrast to other human muscles, there was no functional connection between a population of Ia afferents and some masseter motoneurons. There are two possible explanations for this result. The short-latency, presumably monosynaptic, Ia afferent inputs may not be uniformly distributed to human masseter motoneurons. Alternatively, these inputs may be subject to tonic presynaptic inhibition that is not uniformly distributed throughout the masseter motoneuron pool. PMID- 7776237 TI - Glycogen resynthesis in human muscle fibre types following exercise-induced glycogen depletion. AB - 1. Studies investigating muscle glycogen resynthesis in man have usually examined mixed-fibred biopsies or have used histochemical methods to estimate single fibre resynthesis. Since the accuracy of the latter is open to debate, this study investigated glycogen resynthesis in type I and II fibres using biochemical methods of analysis. 2. Seven subjects performed one-legged cycling exercise to exhaustion. During the initial 2 h of recovery, subjects consumed 3 g of glucose (kg body mass (BM))-1, and a high carbohydrate diet thereafter. Muscle biopsy samples were obtained from both legs at exhaustion, and from the exercised leg after 3, 10 and 24 h of recovery. 3. In the initial 3 h of recovery, there was a 25 +/- 8% higher rate of resynthesis in type I compared with type II fibres (41 +/- 3 and 31 +/- 4 mmol glucosyl units (kg dry mass (DM))-1 h-1, respectively; P < 0.05). Between 3 and 10 h of recovery, resynthesis in type I fibres declined by 60 +/- 13% to 15 +/- 4 mmol glucosyl units (kg DM)-1 h-1 (P < 0.01), whilst the rate in type II fibres was maintained. Good agreement was found when relating the mixed-fibred muscle glycogen concentration to the mean concentration found in type I and type II fibres (r = 0.96). 4. A discrepancy was found to exist with histochemically derived data reported in the literature. The higher initial glycogen resynthesis rate in type I fibres may be attributable to fibre-type differences in glucose uptake and disposal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776238 TI - Respiratory phase resetting and airflow changes induced by swallowing in humans. AB - 1. Relationships between the timing of respiration and deglutition were studied in thirty awake healthy subjects at rest. Deglutition was monitored by submental electromyography, pharyngeal manometry and videofluoroscopy. Respiration was recorded by measurement of oronasal airflow and chest wall movement. Three types of deglutition were studied: injected bolus swallows, spontaneous swallows, and visually cued swallows of boluses previously placed in the mouth. 2. The effect of each swallow on respiratory rhythm was characterized by measurement of cophase, defined as the interval between the onset of deglutitive submental EMG activity to the onset of subsequent rescheduled inspirations. Cophase was determined for swallows initiated at different phases of the respiratory cycle. In all subjects deglutition caused phase resetting of respiratory rhythm. Cophase was largest for swallows initiated near the the inspiratory-expiratory (E-I) transition and smallest for swallows initiated near the expiratory-inspiratory (E I) transition. The pattern of respiratory resetting by deglutition was topologically classified as type 0. This pattern was shown for swallows induced by bolus injection or visual cue, and for spontaneous swallows. 3. The incidence of spontaneous deglutition was influenced by the position of the swallow in the respiratory cycle. Few spontaneous swallows were initiated near the E-I transition whereas most occurred from late inspiration to mid-expiration. 4. Deglutition caused an abrupt decrease in airflow leading to an interval of apnoea, followed by a period of expiration. The duration of deglutition apnoea for spontaneous swallows was shorter than that for 5 ml bolus swallows, and was unaffected by the respiratory phase of swallow initiation. The period of expiration after swallowing was longest for swallows initiated at the I-E transition, and shortest for E-I swallows. 5. The intervals between bolus injection and the onset of deglutition apnoea, and the timing of swallowing events, were not significantly altered by the phase in the respiratory cycle at which swallowing was exhibited. 6. To quantify the relationship between bolus flow and respiration, we determined the latencies between cessation of inspiratory airflow and arrival of the bolus at the larynx (alpha), and between laryngeal bolus departure and resumption of inspiratory airflow (delta). Both values were dependent upon the respiratory phase of swallowing. The lowest values for alpha and delta were found for early-inspiratory and late-expiratory swallows, respectively. 7. We conclude that swallowing causes respiratory phase resetting with a pattern that is characteristic of the strong perturbations of an attractor-cycle oscillator.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776239 TI - 'Non-hypotensive' hypovolaemia reduces ascending aortic dimensions in humans. AB - 1. The notion that small, 'non-hypotensive' reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R-R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross-sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5-20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R-R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means. PMID- 7776240 TI - Activation of P2-purinoreceptors triggered Ca2+ release from InsP3-sensitive internal stores in mammalian oligodendrocytes. AB - 1. The subcellular characteristics of an ATP-induced elevation of the cytoplasmic free calcium concentration ([Ca2+]i) were studied in cultured cells of the oligodendrocyte lineage obtained from mouse cortex and rabbit retina, as well as in oligodendrocytes from mouse corpus callosum slices, using laser scanning confocal microfluorometry. 2. With the stage- and lineage-specific antibodies O4 and O10, three developmental stages within the oligodendrocyte lineage were distinguished prior to Ca2+ recording. 3. Bath application of 1-100 microM ATP induced a transient increase of [Ca2+]i in late precursors and oligodendrocytes but not in early glial precursor cells from retinal and cortical cultures and from corpus callosum slices. This effect of ATP was observed in Ca(2+)-free extracellular solution, suggesting that the ATP-mediated elevation of [Ca2+]i is due to a Ca2+ liberation from intracellular stores. 4. In both late precursors and oligodendrocytes from retina, the amplitude of ATP-induced [Ca2+]i transients was significantly higher in processes as compared with the soma; in cortical cultures such an uneven response was only observed in oligodendrocytes, while in immature cells responses in soma and processes were of similar amplitude. 5. The rank order of potency for the purine and pyrimidine nucleotides was UTP > or = ATP > ADP >> AMP = adenosine = Me-ATP for retinal oligodendrocytes, and ADP > or = ATP >> UTP = AMP = adenosine = Me-ATP for cortical oligodendrocytes. The response to ATP and related nucleotides was blocked by suramin, indicating the involvement of a P2-purinoreceptor in the ATP-mediated [Ca2+]i response. 6. ATP induced elevation of the cytosolic Ca2+ concentration was inhibited by incubating cells with thapsigargin (10 microM) and by intracellular administration of heparin (1 microM). These findings indicate that ATP triggers a release of Ca2+ ions from InsP3-sensitive internal stores. 7. The ATP receptors may play a role in neuron-glial signal transfer; ATP is released as neurotransmitter, but also under pathological conditions from damaged cells. PMID- 7776242 TI - Activation of calcium current in voltage-clamped rat glomerulosa cells by potassium ions. AB - 1. We examined Ca2+ influx mechanisms using the whole-cell patch-clamp technique in primary cultures of rat glomerulosa cells. 2. Depolarization of the plasma membrane, as studied by a stepwise or ramp depolarization technique, activated low-threshold, transient (T-type) and high-threshold, long-lasting (L-type) voltage-dependent calcium channels (VDCCs). 3. Extracellular K+ activated an inward current (Ig1), even in voltage-clamped cells. This phenomenon was observed within the physiological concentration range, beginning at 4.6 mM K+o (as opposed to the control level of 3.6 mM K+o). Increased cell conductance and increased background noise indicated that Ig1 is evoked by enhanced channel activity. Potassium induced no outward current in the voltage range examined (-120 to +60 mV). 4. When non-permeable anions were present only in the pipette and Na+ and Mg2+ were omitted from the bath, K+ still activated the current. Ig1 was blocked by 100 microM cadmium but was insensitive to 2 microM nifedipine or to 300 microM Ni2+. 5. In fluorimetric studies elevation of the cytoplasmic Ca2+ concentration in response to K+ (5.6-13.6 mM) was reduced only partially when VDCCs were blocked with Ni2+ (200 microM) and nifedipine (2 microM). 6. Elevation of the K+ concentration shifted the threshold potential of the T-type calcium channel in the negative direction. 7. In summary, K+ as a ligand activates Ca(2+)-permeable channels in rat glomerulosa cells. This current may contribute to the development of Ca2+ signals in response to stimulation with K+ in the physiological range. The reduction of the activation threshold of the T-type current by K+ may also be of physiological significance. PMID- 7776241 TI - Immunoglobulin E receptor-activated calcium conductance in rat mast cells. AB - 1. The nystatin perforated-patch method was used to record macroscopic currents from anti-trinitrophenyl (TNP) immunoglobulin E (IgE)-sensitized rat basophilic leukaemia (RBL-2H3) cells at 37 degrees C. 2. An inwardly rectifying Ca2+ current (ICa) was activated upon stimulation with the multivalent antigen trinitrophenylated bovine serum albumin (TNP-BSA). Induction of ICa was not observed at room temperature. ICa was reversed and reinduced upon cyclical addition of the monovalent hapten dinitrophenyl (DNP)-lysine and multivalent antigen, indicating that a specific interaction of antigen with IgE was required to elicit ICa. 3. The antigen-induced current was also carried by Ba2+ or Sr2+, and to a lesser extent by Na+, in the nominal absence of Ca2+. ICa did not exhibit time-dependent opening (< or = 1 ms) in response to hyperpolarizing voltage steps to -100 mV, although it did accumulate steady-state inactivation of approximately 40-50% over 100 ms. 4. Two inorganic blockers of antigen-stimulated 45Ca2+ influx and secretion, La3+ and Zn2+, inhibited ICa by approximately 50% at concentrations known to produce 50% block of 45Ca2+ influx. In contrast, cromolyn sodium (0.5 mM) and the L-type Ca2+ channel antagonist nitrendipine (5 microM) had no effect on ICa. 5. ICa also was induced by the intracellular Ca2+ mobilizer thapsigargin. Because the actions of thapsigargin and antigen were not additive, IgE receptor cross-linkage appears to activate the recently described capacitative Ca2+ entry channels. PMID- 7776243 TI - Dopamine D1 receptor modulates the voltage-gated sodium current in rat striatal neurones through a protein kinase A. AB - 1. Whole-cell recordings were made from striatal neurones obtained from neonatal rats and maintained in primary cultures. The effects of dopamine D1 receptor activation were studied on the voltage-gated sodium current. 2. Bath application of a specific D1 agonist, SKF38393 (1 microM), reduced the neuronal excitability recorded in current-clamp by increasing the threshold for generation of action potentials. 3. In voltage-clamp recordings, SKF38393 (1 microM) reversibly reduced the peak amplitude of the sodium current by 37.8 +/- 4.95%. This effect was reversed by the D1 antagonist SCH23390 and was blocked by the intracellular loading of GDP-beta-S (2 mM) suggesting GTP-binding protein involvement. 4. The D1 agonist reduced the peak amplitude of the sodium current without significantly affecting (i) the voltage dependence of the current-voltage relationship, (ii) the voltage dependence of the steady-state activation and inactivation, (iii) the kinetics of the time-dependent inactivation, and (iv) the kinetics of recovery from inactivation. 5. The peak amplitude of the sodium current was progressively reduced by intracellular loading of cyclic AMP-dependent protein kinase (100 U ml 1). 6. Diffusion of a specific peptide inhibitor of the cyclic AMP-dependent protein kinase (PKI; 10 microM) into the cytosol of neurones blocked the effect of the D1 agonist on the sodium current amplitude. 7. These results demonstrate that dopamine acting at the D1 receptor reduces the amplitude of the sodium current without modifying its voltage- and time-dependent properties. This effect involves activation of the cyclic AMP-dependent protein kinase and results in a depression of the striatal neuronal excitability by increasing the threshold for generation of action potentials. PMID- 7776244 TI - Cation regulation of anion current activated by cell swelling in two types of human epithelial cancer cells. AB - 1. In epithelial cells, hyposmotic stress induces visible cell swelling and large Cl- currents, which deactivate on return to isotonic solutions and are abolished by 0.1-0.5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). During depolarizing voltage clamp pulses, the currents activate rapidly and show time dependent relaxation with associated tail currents on return to negative potentials. 2. We used whole-cell and outside-out patch recording to study volume activation of Cl- currents in the epithelial cancer cell lines H69AR and HeLa S5. In a 210 or 160 mosmol l-1 hyposmotic bathing solution containing 90 mM NaCl, 1 mM Ca2+ and 1 mM Mg2+, current relaxation was rapid, occurred positive to the Cl- reversal potential and reduced current to < 30% of its peak level at +100 mV. 3. Replacement of most bath inorganic cations by N-methyl-D-glucamine (NMDG) at constant Cl- concentration and osmolarity eliminated most of the current relaxation and caused an increase in steady-state current levels. Steady-state current was 85 +/- 6% of peak current at +100 mV in NMDG-Cl bath solution. This ratio fell to 55 +/- 2% (n = 5) when 1 mM Mg2+ was re-added to the bath. 4. Re addition of Mg2+ or other Group II metals (Ca2+, Sr2+, Ba2+) induced immediate changes in current relaxation in a dose- and species-dependent manner. Concentrations of Mg2+ as low as 0.1 mM were effective in causing Cl- current relaxation. The IC50 for steady-state current block by external Mg2+ was 1.75 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776245 TI - GABAA receptor activation and the excitability of nerve terminals in the rat posterior pituitary. AB - 1. The activation of GABAA receptors in nerve terminal membranes gates a Cl- channel. Experiments were conducted to determine how the activation of this receptor influences membrane potentials, action potentials and voltage-activated Na+ and K+ channels. 2. When activation of the GABAA receptor produced only conductance changes and no voltage changes, action potentials changed only slightly. The threshold for action potential generation increased by 15%. GABA reduced the broadening of action potentials caused by high frequency stimulation by only 7%. These results indicate that membrane shunting by GABA-gated Cl- channels plays a relatively minor role. 3. By recording changes in the current through K+ channels in cell-attached patches, the activation of GABAA receptors was shown to depolarize the nerve terminal membrane from rest by 14 mV. The GABAB receptor agonist baclofen produced no change in resting membrane potential as measured by this same technique. 4. In whole-terminal recordings under current clamp, with pipettes containing various Cl- concentrations, the GABA-induced depolarization increased with Ecl. The variation with Ecl provided a basis for evaluating the contributions of leak and K+ current in the balance of currents that determines the magnitude of the GABA-induced depolarization. 5. Based on the GABA-induced voltage change and an evaluation of the other currents of significance in the relevant voltage range, an estimate was obtained for ECl of 48 mV to give an estimate for the intracellular Cl- ion concentration of 20 mM. 6. Under conditions allowing both conductance and voltage to change during Cl- channel gating, GABA prevented action potential responses to current injection. Comparable depolarizations produced by adjusting a steady holding current also blocked action potential responses. 7. A depolarization from -60 to -45 mV under voltage clamp inactivated approximately 90% of the Na+ channels and activated a small amount of K+ current. This suggests that inactivation of Na+ channels makes a major contribution to the inhibition of action potentials by GABA. 8. These results are consistent with the hypothesis that GABA inhibits neurosecretion by retarding impulse propagation into the terminal arborization. These results support a depolarization block mechanism for the inhibition of secretion, in which depolarization inactivates Na+ channels sufficiently to block action potentials. PMID- 7776246 TI - Action potential propagation and propagation block by GABA in rat posterior pituitary nerve terminals. AB - 1. A theoretical model was developed to investigate action potential propagation in posterior pituitary nerve terminals. This model was then used to evaluate the efficacy of depolarizing and shunting GABA responses on action potential propagation. 2. Experimental data obtained from the posterior pituitary with patch clamp techniques were used to derive empirical expressions for the voltage and time dependence of the nerve terminal Na+ and K+ channels. The essential structure employed here was based on anatomical and cable data from the posterior pituitary, and consisted of a long cylindrical axon (diameter, 0.5 mm) with a large spherical swelling (diameter, 4-21 mm) in the middle. 3. In the absence of an inhibitory conductance, simulated action potentials propagated with high fidelity through the nerve terminal. Swellings could block propagation, but only when sizes exceeded those observed in the posterior pituitary. Adding axonal branches reduced the critical size only slightly. These results suggested that action potentials invade the entire posterior pituitary nerve terminal in the absence of inhibition or depression. 4. The addition of inhibitory conductance to a swelling caused simulated action potentials to fail at the swelling. Depolarizing inhibitory conductances were 1.6 times more effective than shunting inhibitory conductances in blocking propagation. 5. Inhibitory conductances within the range of experimentally observed magnitudes and localized to swellings in the observed range of sizes were too weak to block simulated action potentials. However, twofold enhancement of GABA responses by neurosteroid resulted in currents strong enough to block propagation in realistic swelling sizes. 6. GABA could block simulated propagation without neurosteroid enhancement provided that GABA was present throughout a region in the order of a few hundred micrometres. For this widespread inhibition depolarizing conductance was 2.2 times more effective than shunting conductance. 7. These results imply two modes of propagation block, one resulting from highly localized release of inhibitory transmitter under conditions potentiating GABA responses, and the other resulting from widespread release of GABA in the absence of receptor potentiation. 8. The Na+ channels of the posterior pituitary nerve terminal have a unique voltage dependence that allows small depolarizations to inactivate without causing activation. The voltage dependence of this Na+ channel may serve as a specialized adaptation that facilitates in allowing small depolarizing conductances to block action potential propagation. PMID- 7776247 TI - Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors. AB - 1. The effect of the divalent cation Zn2+ on inhibitory glycine receptor (GlyR) currents was investigated in rat embryonic spinal cord neurons and Xenopus oocytes expressing recombinant GlyRs. 2. In cultured spinal neurons, Zn2+ potentiated glycine-induced whole-cell currents about 3-fold when applied extracellularly at concentrations of 0.5-10 microM. In contrast, higher concentrations (> 100 microM) of Zn2+ decreased the glycine response. 3. A similar biphasic modulation of glycine-induced currents by Zn2+ was also found with recombinant homo- and hetero-oligomeric GlyRs generated in Xenopus oocytes. Dose-response analysis showed that both the potentiating and inhibitory effects of Zn2+ result from changes in apparent agonist affinity. 4. Analysis of chimeric constructs of the GlyR alpha 1- and beta-subunits revealed that the positive and negative modulatory effects of Zn2+ are mediated by different regions of the alpha 1-subunit. 5. Our data indicate the existence of distinct high- and low affinity Zn2+ binding sites on the ligand-binding alpha-subunits of the GlyR. These sites may be implicated in the regulation of synaptic efficacy within glycinergic pathways. PMID- 7776248 TI - Subthreshold oscillations and resonant frequency in guinea-pig cortical neurons: physiology and modelling. AB - 1. Intracellular recordings were made from neurons in slices from guinea-pig frontal cortex. In 50% of the cells, sustained subthreshold voltage oscillations were evoked by long (> 6 s) depolarizing pulses. The peak-to-peak amplitude of these oscillations was less than 5 mV and the frequency was voltage dependent, increasing with depolarization from 4 (near rest) to 20 Hz (at 30 mV depolarization). 2. The impedance-frequency relationship of both oscillating and non-oscillating cells was studied by intracellular injection of sinusoidal current with linearly changing frequency. In most cells, a peak in the impedance magnitude (resonant behaviour) was observed at depolarized levels. The frequency of the peak impedance (peak frequency) increased with depolarization from 3 (near rest) to 15 Hz (at 30 mV depolarization). 3. Application of TTX (10(-6) M) significantly decreased the impedance magnitude near the peak frequency. The subthreshold oscillations, however, as well as the action potentials, were fully blocked by TTX. On the other hand, TEA (15 mM) and Cs+ (5 mM) abolished both the subthreshold oscillations and the resonant behaviour. Replacing Ca2+ with Co2+ (5 mM) or Ni2+ (1 mM) did not abolish the subthreshold oscillations. The peak in the frequency-response curve was only slightly reduced. 4. An isopotential membrane model, consisting of a leak current, a fast persistent sodium current, a slow non inactivating potassium current (with the kinetics of the M-current) and membrane capacitance, is sufficient to produce both voltage oscillations and resonant behaviour. The kinetics of the K+ current by itself is sufficient to produce resonance behaviour. The Na+ current amplifies the peak impedance magnitude and is essential for the generation of subthreshold oscillation. The model correctly predicted the behaviour of the frequency response before and after TTX and TEA application, as well as the relation between the expected passive impedance and the experimental impedance. 5. We speculate that the tendency of the neurons to generate voltage signals at a certain frequency (as a result of the subthreshold oscillations) and to preferentially respond to inputs arriving at the same frequency (the resonance behaviour) promotes population activity at that preferred frequency. PMID- 7776249 TI - Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. AB - 1. The cellular basis for generation of spindle waves and a slower synchronized oscillation resembling absence seizures was investigated with extracellular and intracellular recording techniques in slices of ferret dorsal lateral geniculate nucleus (LGNd) maintained in vitro. 2. Intracellular recording from LGNd relay cells in vitro revealed that spindle waves occurred once every 3-30 s and were associated with barrages of inhibitory postsynaptic potentials (IPSPs) occurring at a frequency of 6-10 Hz. These IPSPs resulted in the generation of rebound low threshold Ca2+ spikes at 2-4 Hz, owing to the intrinsic propensity of LGNd relay cells to generate oscillatory burst firing in this frequency range. These rebound bursts of action potentials were highly synchronized with local multiunit and single unit activity. 3. The spindle wave-associated IPSPs in LGNd relay cells exhibited a mean reversal potential of -86 mV. This reversal potential was shifted to more depolarized membrane potentials with the intracellular injection of Cl- through the use of KCl-filled microelectrodes. Simultaneous recording from the perigeniculate nucleus (PGN) and LGNd revealed the IPSPs to be synchronous with the occurrence of burst firing in the PGN. Excitation of PGN neurons with local electrical stimulation after pharmacological block of excitatory amino acid transmission resulted in bicuculline-sensitive IPSPs in relay neurons similar in amplitude and time course to those occurring during spindle waves. 4. Application of (-)-bicuculline methiodide resulted in the abolition of spindle wave associated IPSPs or in the slowing of the rate of rise, an increase in amplitude and a prolongation of these IPSPs; this resulted in a synchronized 2-4 Hz oscillation, in which each relay cell strongly burst on nearly every cycle, thus forming a paroxysmal event. Bath application of the GABAB receptor antagonist 2 OH-saclofen blocked these slowed oscillations, indicating that they are mediated by the activation of GABAB receptors. In contrast, pharmacological antagonism of GABAB receptors did not block the generation of normal spindle waves. 5. These and other results indicate that spindle waves are generated in the ferret LGNd in vitro as a network phenomenon occurring through an interaction between the relay cells of the LGNd and the GABAergic neurons of the PGN. We propose that burst firing in PGN cells hyperpolarizes relay neurons through activation of GABAA receptors. These IPSPs result in rebound burst firing in LGNd cells, which then excite PGN neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776251 TI - Step phase-related excitability changes in spino-olivocerebellar paths to the c1 and c3 zones in cat cerebellum. AB - 1. Chronically implanted microwires were used to record extracellular field potentials generated in the c1 and c3 zones in the cortex of lobules V and VI of the cerebellum by non-noxious stimuli delivered to the superficial radial nerve in the ipsilateral forelimb. Responses due to input via climbing fibre afferents were studied; their latency and other characteristics identified them as mediated mainly via the dorsal funiculus spino-olivocerebellar path (DF-SOCP). 2. Responses at individual sites were studied repeatedly with a range of stimulus intensities and during two different behaviours: quiet rest and steady walking on an exercise belt. For responses during walking, step histograms were constructed showing response mean size during different tenths of the step cycle in the ipsilateral forelimb, both in absolute terms and relative to mean size during rest. 3. Step histograms for the same site on different days or different stimulus intensities varied appreciably in form but in both cases the timing of the largest response was usually the same or shifted by only one step tenth. 4. In both zones the largest responses during walking occurred overwhelmingly during the E1 step phase when the limb is extended forwards and down to establish footfall. Least responses were much less uniform in timing but were mostly during stance, particularly its early (E2) part. 5. In many histograms the smallest responses were smaller in mean size than the responses during rest while the largest were larger. These changes were not paralleled by changes in nerve volley size, so presumably reflect step-related central changes in pathway excitability. Facilitations and depressions were differently affected by stimulus intensity and sometimes occurred independently, suggesting generation by separate mechanisms. 6. In both zones there were differences between recording sites which suggests that different DF-SOCP subcomponents innervate different parts of the zones. However, no systematic differences could be firmly established between the medial and lateral subzones of the c1 zone. 7. The results are discussed in relation to the hypothesis that the DF-SOCP constitutes the afferent limb of a transcerebellar mechanism involved in adapting the evolving step. PMID- 7776250 TI - Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro. AB - 1. The cellular mechanisms by which neurons of the ferret perigeniculate nucleus (PGN) participate in the generation of spindle waves and slowed absence seizure like oscillations were investigated with intracellular and extracellular recording techniques in geniculate slices maintained in vitro. 2. During spindle wave generation, PGN neurons generated repetitive (2-9 Hz) high frequency (up to 500 Hz) burst discharges mediated by the activation of a low threshold Ca2+ spike by the arrival of barrages of excitatory postsynaptic potentials (EPSPs). In most PGN cells at resting membrane potentials (-60 to -70 mV) spindle waves were associated with a progressive hyperpolarization that persisted as a prolonged after-hyperpolarization. 3. The EPSPs occurring in PGN cells were highly synchronized with burst firing in the neighbouring portion of the dorsal lateral geniculate nucleus (LGNd) and were intermixed with short duration inhibitory postsynaptic potentials (IPSPs). After block of GABAergic receptors, the EPSPs occurring during the generation of spindle waves reversed polarity at around 0 mV. In addition, these EPSPs were completely blocked with the bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as was spindle wave generation in both the PGN and LGNd. 4. Slowing the intraspindle frequency to 2-4 Hz with pharmacological block of GABAA receptors resulted in a marked increase in the intensity of burst firing by PGN cells such that the number of action potentials per burst increased from a maximum of thirteen to a maximum of sixty. Block of GABAA receptors also resulted in a marked increase in the amplitude and duration of the EPSP barrages arriving from the relay laminae during generation of the slowed oscillation. 5. These findings indicate that spindle waves are generated in the ferret LGNd in vitro through an interaction between the GABAergic neurons of the PGN and relay neurons, such that burst firing in relay neurons activates a barrage of EPSPs and a subsequent low threshold Ca2+ spike in PGN cells. This activation of PGN neurons inhibits a substantial number of relay cells, a few of which rebound burst after this IPSP, thus starting the cycle again. Block of GABAA receptors results in a marked enhancement of activity in PGN cells through increased excitation from relay cells and disinhibition from neighbouring PGN cells. This increased activity in PGN neurons results in a markedly enhanced activation of GABAB receptors in relay neurons and the subsequent generation of paroxysmal activity that is similar to that associated with absence seizures. PMID- 7776252 TI - Pivotal role of phosphate chain length in vasoconstrictor versus vasodilator actions of adenine dinucleotides in rat mesenteric arteries. AB - 1. The isolated perfused rat mesenteric arterial bed was used to examine the activity of the adenine dinucleotides: beta-nicotinamide adenine dinucleotide (NAD); beta-nicotinamide adenine dinucleotide phosphate (NADP); flavin adenine dinucleotide (FAD); and of the alpha,omega-diadenosine polyphosphates: adenylyl adenosine (AP1A); P1,P2-diadenosine pyrophosphate (AP2A); P1,P3-diadenosine triphosphate (AP3A); P1,P4-diadenosine tetraphosphate (AP4A); P1,P5-diadenosine pentaphosphate (AP5A); P1,P6-diadenosine hexaphosphate (AP6A). Responses were compared with those of ADP, ATP, 2-methylthio-ATP (2-meSATP) and alpha,beta methylene ATP (alpha,beta-meATP). 2. In basal tone preparations mono- and dinucleotides elicited vasoconstriction with the order of potency: alpha,beta meATP > or = AP5A > or = AP6A > or = AP4A > or = 2-meSATP >> ATP >> ADP. The dinucleotides NAD, NADP, FAD, AP1A, AP2A and AP3A had no effect. 3. The P2X purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (30 microM) virtually abolished vasoconstrictor responses to AP4A, AP5A and AP6A. 4. Auto- and cross-desensitization of vasoconstrictor responses to AP4A, AP5A, AP6A, ATP and alpha,beta-meATP were observed. 5. In raised tone preparations nucleotides elicited endothelium-dependent vasodilatation with the order of potency: 2-meSATP = ADP > ATP > AP3A > AP2A > AP1A = NADP = FAD > NAD. The nucleotides AP4A, AP5A, AP6A and alpha,beta-meATP had no vasodilator effects. 6. It is concluded that the alpha,omega-adenine dinucleotides AP4A, AP5A and AP6A elicit vasoconstriction, but not vasodilatation, in the rat mesenteric arterial bed via P2x-purinoceptors. In contrast, the dinucleotides NADP, FAD, AP1A, AP2A and AP3A elicit vasodilatation, but not vasoconstriction, via endothelial P2Y purinoceptors. 7. It is suggested that there is a crucial relationship between the structure of the alpha,omega-diadenosine polyphosphates and their activity at P2X- and P2Y-purinoceptors with a pivotal role played by the polyphosphate chain. Molecules with four or more phosphates are vasoconstrictors, while those with three or less phosphates are vasodilators. PMID- 7776253 TI - Flow-dependent regulation of arteriolar diameter in rat skeletal muscle in situ: role of endothelium-derived relaxing factor and prostanoids. AB - 1. Arteriolar diameter in the resting rat spinotrapezius muscle was studied by intravital video microscopy before and after blockade of the L-arginine-EDRF (NG nitro-L-arginine, L-NNA) or the cyclo-oxygenase-prostacyclin (indomethacin) pathway. Blockade of either pathway leads to a decrease of arteriolar diameter of 25-40%, while the combined blockade of both results in vasoconstriction of 50 60%. 2. Alteration of blood flow velocity elicited by partial micropipette occlusion induces corresponding changes of vessel diameter. The flow-dependent diameter response is reduced by about 80% by L-NNA. By contrast, blockade of prostanoid production shows no significant influence on vessel response to blood flow alteration in the range tested. 3. Transient overshooting vasodilatation is seen for about 1 min following the sudden restoration of flow velocity subsequent to occlusion. In contrast to the initial phase of this response, the late phase is blocked by L-NNA. 4. The findings suggest that basal release of endothelium derived relaxing factor (EDRF) and prostanoids leads to additive and independent dilator effects, and that flow-dependent diameter changes are primarily mediated by EDRF. 5. If present data are compared with literature reports, it appears that arterial flow sensitivity is most pronounced in the smallest vessels. In such vessels, flow-dependent dilatation will amplify even small changes of volume flow by more than four times. PMID- 7776254 TI - Prevention of the excitatory actions of bradykinin by inhibition of PGI2 formation in nodose neurones of the guinea-pig. AB - 1. Intracellular recordings were made from neurones in intact guinea-pig nodose ganglia in vitro and from acutely isolated adult guinea-pig and rabbit nodose neurons to study a bradykinin (BK)-mediated block of a slow spike after hyperpolarization (AHPslow) that is prominent in 30-40% of these neurones. 2. BK (100 nM) reversibly blocked the AHPslow, resulting in an ablation of the spike accommodative properties of these neurones. The B1 BK receptor agonist [des-Arg9] BK did not mimic or prevent the actions of BK. In contrast, the B2 BK receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE 140) prevented BK-induced block of the AHPslow and the effect of BK on spike frequency adaptation. 3. The BK block of the AHPslow in acutely dissociated neurones was prevented by indomethacin, indicating that this BK effect was dependent upon a cyclo-oxygenase metabolite intrinsic to these neurones. 4. One to twenty femtomoles of the prostanoids PGE2, PGD2, 9 alpha, 11 beta-PGF2 (a metabolite of PGD2), PGF2 alpha, TxB2 and PGI2 were released spontaneously from a nodose ganglion in 15 min. BK (100 nM) selectively increased PGI2 release 2.8-fold without affecting the release of the other prostanoids. Treatment with 10 microM tranylcypromine (TCP), a putative PGI2 synthase inhibitor, completely prevented the BK-induced release of PGI2. 5. In the presence of 10 microM TCP, BK no longer produced significant effects on the AHPslow. In contrast, 10 microM TCP did not prevent PGI2 from blocking the AHPslow. 6. These results suggest that vagal afferents that exhibit AHPslow also possess the B2 type of BK receptor. Activation of these BK receptors results in the production of PGI2, which in turn controls spike frequency adaptation by affecting the amplitude of the AHPslow. PMID- 7776255 TI - Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. AB - 1. Mechano- and heat-sensitive A fibre nociceptors (AMHs) and C fibre nociceptors (CMHs) in hairy skin (forty-six AMHs and twenty-one CMHs) and in glabrous skin (fifty-nine AMHs and ten CMHs) of anaesthetized monkeys were tested with a 30 s, 53 degrees C heat stimulus, delivered by a laser thermal stimulator (0.1 s rise time, 7.5 mm diameter). 2. Two types of heat response were observed in hairy skin AMHs. Type I AMHs had a peak discharge towards the end of the stimulus, response latencies to heat of up to several seconds, a median heat threshold greater than 53 degrees C, and a mean conduction velocity of 25 m s-1 (n = 33). Type II AMHs had a peak discharge within 1-3 s, a mean response latency of 120 ms, a median heat threshold of 46 degrees C, and a mean conduction velocity of 15 m s-1 (n = 13). Type I AMH fibres were sensitized to heat, whereas heat responses of type II AMHs were suppressed following the intense heat stimulus. 3. In glabrous skin, only type I AMHs were found. The absence of type II AMHs is consistent with the absence of first pain to heat in glabrous skin. 4. C fibre nociceptors in hairy skin had a peak discharge near stimulus onset, a mean response latency of 100 ms and a median heat threshold of 41 degrees C. Heat responses of CMHs in glabrous skin were not significantly different from those in hairy skin. 5. Only type II AMHs had response latencies that were short enough to explain first pain to heat. Heat thresholds of type II AMHs were significantly higher than those of CMHs. 6. These results suggest two different heat transduction mechanisms in nociceptive afferents. For one, heat energy is quickly transduced into action potentials, and the peak discharge is reached soon after stimulus onset. For the other, the transduction of heat is distinctly slower, and the peak discharge occurs near the end of the stimulus. Chemically mediated sensitization may be involved in the second transduction mechanism. PMID- 7776256 TI - Functional classification of afferent phrenic nerve fibres and diaphragmatic receptors in cats. AB - 1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs, ergoceptors and nociceptors. The sensory diaphragmatic outflow to the spinal cord is somatotopically organized. PMID- 7776257 TI - Adenosinergic modulation of respiratory neurones and hypoxic responses in the anaesthetized cat. AB - 1. The modulatory effects of intracellularly injected adenosine on membrane potential, input resistance and spontaneous or evoked synaptic activity were determined in respiratory neurones of the ventral respiratory group. 2. The membrane potential hyperpolarized and sometimes reached values which were beyond the equilibrium potential of Cl(-)-dependent IPSPs. At the same time, neuronal input resistance decreased. 3. Spontaneous and stimulus-evoked postsynaptic activities were decreased, as were mean respiratory drive potentials. 4. Systemic injection of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine (DPCPX; 0.01-0.05 mg kg-1) resulted in an increase in mean peak phrenic nerve activity when arterial chemoreceptors were denervated. In contrast, phrenic nerve activity decreased when arterial chemoreceptors were left intact. 5. The depressant effect of adenosine on synaptic activity was abolished after systemic DPCPX administration. DPCPX caused an increase in respiratory drive potentials, increased the amplitude of stimulus-evoked IPSPs, and hyperpolarized membrane potential. 6. Administration of DPCPX blocked the early hypoxic depression of stimulus-evoked IPSPs, doubled the delay of onset of hypoxic apnoea and shortened the time necessary for recovery of the respiratory rhythm. 7. The data indicate that adenosine acts on pre- and postsynaptic A1 receptors resulting in postsynaptic membrane hyperpolarization and depression of synaptic transmission. Blockade of A1 receptors increases respiratory activity, indicating that adenosine A1 receptors are tonically activated under control conditions. Further activation contributes to the hypoxic depression of synaptic transmission in the respiratory network. PMID- 7776258 TI - Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects. AB - 1. Impulses in single nerve fibres from the lateral antebrachial cutaneous nerve were recorded using the microneurography technique in human subjects. 2. In a sample of fifty-five mechanoreceptive units with fast-conducting nerve fibres, five types were identified, i.e. SAI (slowly adapting type I, Merkel), SAII (slowly adapting type II, Ruffini), hair units, field units and Pacinian-type units. The latter three unit types were all rapidly adapting. 3. The detailed structure of thirty-five receptive fields of SAI, SAII, hair and field units was explored with a method which was objective and independent of the experimenter's skill and experience. A lightweight probe was used to scan the receptive field area in a series of tracks 0.23 mm apart while single-unit activity was recorded. 4. SAI fields were small and composed of two to four well-separated high sensitivity spots and often, in addition, one minor spot of lower sensitivity. SAII units typically fired spontaneously at a low and regular rate. Most fields consisted of one single spot of high sensitivity with diffuse borders. The hair units innervated ten to thirty-three (or more) hairs, which were evenly distributed over a large area. The field units were characterized by a number of small and closely packed high-sensitivity spots with diffuse borders. A conservative estimate indicated eleven spots per unit. 5. The findings indicate that the sheet of mechanoreceptors on the skin of the forearm is distinctly different from that on the dorsum of the hand and in the face. It seems reasonable to assume that the former is more representative for the hairy skin covering the main parts of the body. PMID- 7776259 TI - Human perceptual learning in identifying the oblique orientation: retinotopy, orientation specificity and monocularity. AB - 1. Human perceptual learning in discrimination of the oblique orientation was studied using psychophysical methods. Subjects were trained daily to improve their ability to identify the orientation of a circular 2.5 deg diameter unidimensional noise field. Dramatic improvements in sensitivity to contour orientation occurred over a period of 15-20 days. The improved performance persisted for several months. Improvement was more evident between daily sessions than within sessions. This was partly due to fatigue interfering with the learning effect. Moreover, a consolidation period seemed to be required. 2. Improvement was restricted to the position of the stimulus being trained. This position dependency of the learning effect proved very precise. After training at a specific stimulus position, merely displacing the stimulus to an adjacent position caused a marked increase in thresholds. 3. No transfer of the training effect was observed between orientations. Following a shift of 90 deg away from the trained orientation, performance fell, even below the initial level. 4. We observed complete to almost complete transfer between the two eyes. 5. Our results suggest plastic changes at a level of the visual processing stream where input from both eyes has come together, but where generalization for spatial localization and orientation has not yet occurred. PMID- 7776260 TI - Distribution of p21ras during primary palate formation of non-cleft and cleft strains of mice. AB - Cleft lip, with or without cleft palate, is one of the most common defects in craniofacial formation. The primary palatogenesis of mice is similar to that of humans and spontaneous cleft lip is associated with genotype in both mice and humans. To investigate the temporal and spatial expression of ras genes in cleft (A/WySn) and non-cleft strains of mice (BALB/cBy), a broad spectrum ras antibody was used. Positive staining was found in ectodermal, mesenchymal, and neuroepithelial cells of facial prominences before the primary palate formation stage (10 d 20 hr) in both strains. During the primary palate formation stage (11 d 20 hr), positive staining was found in the ectodermal and mesenchymal cells of the facial prominences of the non-cleft strain but not in those of the cleft strain. These results suggest ras genes may play a role in the primary palatogenesis of mice. Cleft lip could be associated with the deficiency of ras gene expression during primary palate formation of mice. PMID- 7776261 TI - Detection of Epstein-Barr virus DNA in tongue tissues from AIDS autopsies without clinical evidence of oral hairy leukoplakia. AB - Epstein-Barr virus (EBV) DNA was detected by in situ hybridization at 3 sites of 30 samples taken from clinically normal lateral border of tongue mucosa from 15 AIDS autopsies and in none of 20 samples from 10 controls. The first positive case showed a thin layer of parakeratosis correlated with positive signals for EBV in one area and an adjacent area without obvious parakeratosis was also positive for EBV. These findings were present on both sides of the tongue. The second case was unilaterally positive for EBV and parakeratosis was absent. The hybridization signals were localised to koilocyte-like cells in the stratum spinosum, as in oral hairy leukoplakia (OHL). These observations suggest that the in situ hybridization technique can detect very early or subclinical OHL, and supports the role of EBV in the pathogenesis of this lesion. PMID- 7776262 TI - Proteoglycan changes in carcinogen (4NQO)-treated rat tongue mucosa. AB - The purpose of this study was to undertake preliminary analyses of the extracellular proteoglycans in carcinogen [4-nitroquinoline N-oxide (4NQO)] treated rat tongue mucosa. Experimental rats were exposed to twice-weekly applications of 4NQO in propylene glycol for six months, after which the animals were killed. Control and 4NQO-treated tissues were subjected to sequential aqueous extractions of proteoglycans under associative and dissociative conditions, followed by alkaline cleavage of protein-glycosaminoglycan linkages to yield a glycosaminoglycan residue. Tissues subjected to 4NQO applications contained smaller proportions of proteoglycans which were readily soluble under associative and dissociative conditions. Proportionately more proteoglycan remained strongly associated with other intercellular tissue components, being released only by alkaline cleavage. These biochemical alterations in preinvasive 4NQO-treated epithelium and connective tissues, together with an observed associated change in water retention by the connective tissue, occurred prior to actual neoplastic invasion and suggest differences in macromolecular conformation and orderliness. We hypothesize that these changes are related to the phenomenon of neoplastic epithelial invasion. PMID- 7776263 TI - Induction of carcinomas and sarcomas by 9,10-dimethyl-1,2-benzanthracene administration into the hamster maxillary sinus. AB - To determine whether the local administration of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the hamster maxillary sinus induced carcinoma at the injected site, hamsters were injected with 30 microliters of 0.5% solution of DMBA in dimethyl sulfoxide (DMSO) through the infraorbital foramen into the maxillary sinus once weekly for 10 weeks (Group 2). Another group of hamsters (Group 1) received similar injections of 30 microliters of DMSO only. In a third group of animals (Group 3), a roll of oxycellulose was inserted into the maxillary sinus and 40 microliters of a 2% solution of DMBA in DMSO was injected once. Sinonasal carcinomas were demonstrated in 73% (8/11) of the hamsters in Group 2 and sarcomas were shown in 73% (8/11) of the hamsters in Group 3, as well as some carcinomas. No tumors were seen in the Group 1 hamsters. Histologic examination revealed squamous cell carcinomas arising from the surface epithelium and submucous glands of the nasal cavity and maxillary sinus. These findings indicate that the intrasinal administration of a 0.5% solution of DMBA in DMSO is a reliable method for inducing maxillary sinus cancer. PMID- 7776264 TI - Ultrastructural finding of vascular degeneration in fibrodysplasia ossificans progressiva (FOP). AB - The masseter and temporalis muscles were investigated ultrastructurally in 2 patients having fibrodysplasia ossificans progressiva (FOP). Results showed atrophy and necrosis of muscle fibres. Both cases contained cartilage which was calcified in the second case and was associated with degenerating chondrocytes. The blood vessels showed various changes, with haematoma formation and large fibrin deposits. Some of the fibrin deposits seen in the second case were surrounded with cartilage. This suggests that the cartilage probably forms as a reaction to an old haemorrhage. It is possible that the effect of the mutant gene found in FOP is on blood vessels rather than the normal regulatory mechanisms of the inducible osteogenic precursor cells. These degenerating blood vessels often result in haemorrhage and fibrin deposits; the fibrosis, cartilage or bone formation are probably secondary changes. Amianthoid fibres found in the tendon of the temporalis muscles of the second case, together with the other changes of fibrosis and cartilage formation, account for the severe restricted mouth opening suffered by these patients. PMID- 7776265 TI - Histochemical study of lectin binding in the human fetal minor salivary glands. AB - The emerging synthesis of glycoconjugates containing specific oligosaccharides in developing human fetal labial and lingual salivary glands has been investigated by lectin histochemistry. An avidin-biotin technique was used to study the binding of lectins from Ulex europeus I (UEA-I), Dolichos biflorus (DBA), Glycine maximus (SBA), Helix pomatia (HPA), Arachis hypogaea (PNA) and Triticum vulgare (WGA) to specific sugars on sections of tissue from labial glands, glands of Blandin and Nuhn, glands of von Ebner and the dorsoposterior lingual salivary glands. Incipient synthesis of glycoconjugates in early glands and their presence in the cells and ducts of the later glands was shown. The study also showed a time-related increase in both staining intensity and binding sites of serous acinar cells from all glands and for all lectins used. For mucous cells, peak intensity of staining was reached by the middle phase of development. During later gland development this intensity was maintained in dorsoposterior lingual glands but tended to decline in labial glands. The various lectins showed different degrees of binding but UEA-I lectin generally bound the L-fucose sugar group in all salivary glands at all gestational ages. The results showed that lectins appear to bind to the oligosaccharides on epithelial cell surfaces of fetal salivary glands at all stages of development. The degree of change depends upon the stage of differentiation and maturation of the glands. PMID- 7776266 TI - Oral manifestations in glycogen storage disease type 1b. AB - Glycogen storage disease type 1b is a rare metabolic disorder which affects the transport system of glucose-6-phosphatase metabolism. As a result, hepatomegaly, failure to thrive, renal dysfunction and recurrent infections occur in affected patients. In this paper, the oral complications in three children with glycogen storage disease type 1b are discussed. Oral ulcers were a common finding, probably due to severe neutropenia and impaired neutrophil migration which characterises the onset of this rare disorder. PMID- 7776267 TI - Parallel pathways coordinate crawling in the medicinal leech, Hirudo medicinalis. AB - Changes in the behavior of crawling leeches were investigated after various kinds of manipulations, including selective transection or inactivation of body parts, as well as partial or complete transection of the central nerve cord, using a frame-by-frame analysis of video tapes of the crawling animals. From these studies, we found that: 1. Leeches made rhythmic crawling cycles even after their suckers were prevented from contacting the substrate by covering them over with glue. Hence, engagement and disengagement of the suckers are not necessary links in the crawling cycle. 2. Cutting the small, medial connective (Faivre's nerve) had no influence on crawling, but contraction during the whole-body shortening reflex was interrupted. Thus two behaviors which use the same motor output (i.e., whole-body shortening and the contraction phase of crawling) are mediated by two different pathways. 3. Cutting all the connectives between two ganglia in the middle of the leech resulted in a loss of coordination between the parts of the animal on either side of the cut. Therefore, temporally coordinated sucker activity must be mediated through these connectives. 4. Pieces of leech bodies produced by complete transection produced rhythmic crawling cycles as long as the pieces included the head or tail plus 2-4 adjacent midbody segments. In all cases, the crawling movements progressed without delays as the movements reached the cut ends. Pieces of animals that included only midbody segments did not produce crawling movements. 5. These results can be explained by a model composed of intersegmental pathways for both elongation and contraction, circuits in the head and tail brains that switch between elongation and contraction, and both ascending and descending inhibitory influences that determine when the cycle switches from elongation to contraction and back again. PMID- 7776268 TI - Stiffness changes in chick hair bundles following in vitro overstimulation. AB - 1. The in vitro effect of intense stimulation on the micromechanical stiffness of hair cell sensory hair bundles was studied at three locations on the chick basilar papilla. Threshold levels of hair bundle motion, produced by a water jet stimulus, were examined before and after exposure to a 300 Hz water jet stimulus set at 25 dB above the pre-exposure threshold level. 2. Threshold levels of motion were systematically examined in 8 unexposed control cells. The level of water jet stimulus needed to achieve the detection threshold of motion remained constant in these cells when periodically tested over a 36.5-min interval. 3. Post-exposure changes in the motion detection threshold of hair bundles were examined in 82 hair bundles, and a number of effects were identified: 2.4% of the hair bundles showed no threshold changes; 31.7% of the hair bundles had threshold shifts which indicated an increase in stiffness; 18.3% exhibited a threshold shift that indicated a decrease in hair bundle stiffness, but with no recovery; and 47.6% had thresholds that indicated a decrease in hair bundle stiffness with recovery to pre-exposure levels within 16-18 min. 4. The results suggest that chick hair bundles exhibit complex and varied responses to overstimulation which are very different from that seen in the mammal. PMID- 7776269 TI - Acoustic response properties of single neurons in the central posterior nucleus of the thalamus of the goldfish, Carassius auratus. AB - Acoustic responses were recorded extracellularly from single neurons in the thalamic central posterior nucleus (CP). Spontaneous activity, best sensitivity, and sharpness of tuning (Q10dB) of CP neurons ranged from 0 to 36 spikes/s, -40 to 5 dB re: 1 dyne/cm2, and 0.18 to 1.80, respectively. The distribution of characteristic frequency (CF) was nonuniform with a mode at 195 Hz. Temporal response patterns of CP neurons (N = 60) were categorized into three groups: phasic (25%), tonic chopper-like (22%), and tonic nonchopper-like (53%) on the basis of peri-stimulus time and inter-spike interval histograms. Most CP neurons (90%) did not phase-lock to tones, and none phase-locked strongly. The properties of CP neurons are similar to those of the midbrain torus semicircularis neurons in spontaneous rates, best sensitivities, nonuniform CF distributions, and in exhibiting level-independent best frequencies. Both CP and toral neurons show a diversity of response patterns resembling those found in the mammalian central auditory system. However, CP neurons have broader tuning and less phase-locking than toral neurons, suggesting different roles in auditory processing. While peripheral frequency analysis is enhanced at the midbrain level, the integration of frequency-selective channels in the thalamus may function in the processing of wideband spectra characteristic of natural sound sources. PMID- 7776270 TI - Current blood transfusion practice in aortic aneurysm surgery in Scotland. The Scottish Vascular Audit Group. AB - A questionnaire on current practice in blood transfusion during aortic aneurysm repair was sent to all consultant surgeons with a vascular interest practising in Scotland. Replies were received from 31 surgeons. A blood ordering schedule was operated by 29 surgeons for elective operations and 26 surgeons for emergency operations. The mean number of units of red cell concentrate ordered was 4.7 units for elective operations (range 3-8 units) and 8 units for emergency operations (range 6-12 units). The time estimated to obtain red cell concentrate was 38.2 min (range 15-90 min) for a new request and 8.8 min (range 2-30 min) to obtain further blood in a patient already crossmatched. Blood conservation techniques employed included the use of low porosity or sealed grafts by 86% of surgeons. Autotransfusion was used by six surgeons, but only regularly by three surgeons. One surgeon used pre-deposit autologous transfusion and one used preoperative haemodilution. Intravenous heparin was used by 90% of surgeons during elective operations and by 16% of surgeons during emergency operations. Most surgeons used a standard dose of 5000 units of heparin. PMID- 7776271 TI - Non-specific abdominal pain: a safe diagnosis? AB - Non-specific abdominal pain (NSAP) is a benign condition with low morbidity. This follow-up study of 82 patients discharged from an emergency department after presenting with abdominal pain, during 1 calendar month, has shown that only 9.6% were diagnosed as having NSAP. It has been shown previously that 34.9% to 45.6% of patients presenting to an emergency department with abdominal pain will have NSAP. One large study showed that 88% of NSAP had improved or resolved at 2-3 weeks without specific treatment and few required subsequent hospitalization. In this study a number of patients were given diagnoses which could not be supported from the history or investigations. This is a potentially dangerous practice. NSAP is a diagnosis of exclusion and the patient may be reassured that the condition is most likely benign or self limiting and allowed home. PMID- 7776272 TI - Mesenteric ischaemia: prognostic factors and influence of delay upon outcome. AB - The case records of 43 patients with acute mesenteric ischaemia who presented to the Professorial Surgical Unit, Aberdeen Royal Infirmary between January 1982 and December 1992 were examined. Principal presenting clinical symptoms were acute abdominal pain (100%) with diarrhoea in 44% of patients. Abdominal examination revealed diffuse non-specific tenderness in 48%, with signs of peritonitis in 52% of patients. In 22 of the 43 (51%) patients there was a delay in diagnosis (greater than 12 h from the onset of pain). The overall mortality was 70%, and three significant prognostic factors were identified--surviving patients had a delay in diagnosis of less than 12 h, a normal chest radiograph and a higher arterial paO2, (10.0 +/- 1.0 vs 7.7 +/- 1.2, P < 0.05, vs non-survivors), on admission to the surgical unit. Twenty-five of the 29 non-surviving patients had extensive infarction of small and large intestine, compared with only 1 of the 14 surviving patients (P < 0.05). PMID- 7776273 TI - Open versus laparoscopic cholecystectomy: a comparison of postoperative temperature. AB - Laparoscopic cholecystectomy has been shown to allow better postoperative pulmonary function than open cholecystectomy, with less incidence of lung atelectasis. As atelectasis following abdominal surgery is responsible for most febrile episodes in the first 48 h, it was postulated that with minimally invasive surgery there may be a parallel improvement in the incidence of postoperative fever. This study was designed to evaluate this hypothesis. Seventy eight patients were randomly divided into two groups. Thirty-eight had an open cholecystectomy and 40 underwent the laparoscopic approach. Twenty-one of the 38 patients (55%) following open cholecystectomy had early febrile episodes compared with only 6 of the 40 (15%) in the laparoscopic cholecystectomy group. We concluded that there was a lower incidence of febrile episodes following laparoscopic cholecystectomy and suggest that this was related to improved pulmonary function and minimal surgical trauma. PMID- 7776274 TI - Large bowel herniation after laparoscopic cholecystectomy. PMID- 7776275 TI - Ergonomics, engineering and surgery of endosurgical dissection. AB - Ergonomic analysis of the tasks of endosurgery helps in the design of instruments and tasks, and in decreasing the mismatch between human capacities and technology. It requires the study of the constraints of working through narrow fixed ports and an understanding of how the processes of gripping and dividing tissue are determined by its mechanical properties. This formal approach may offer more than trial-and-error evolution and haphazard solutions to problems by quicker general answers, with shorter learning curves, greater productivity and fewer errors, and decreased operator frustration. The first and ultimate benefit is for patients undergoing endosurgery. PMID- 7776276 TI - Distal first metatarsal osteotomy and adductor release as a treatment of hallux valgus. AB - A combined bony and soft tissue procedure is reported as a treatment of hallux valgus. Satisfactory subjective and objective results were obtained at an average follow-up of 49.6 months. There was a 21% incidence of avascular necrosis of the first metatarsal head, four out of the 38 patients (10.5%) having developed a varus deformity at follow-up. PMID- 7776278 TI - The crushed foot. AB - Crush-type injuries are potentially serious, and the foot is particularly vulnerable. Despite this, they are often inappropriately dismissed as trivial when first seen. This tendency to underestimate the severity of the injury is reinforced by unimpressive radiographic findings. Poor initial management may have significant physical and medicolegal implications. Four recently treated cases illustrate the covert severity of crush injuries to the foot. PMID- 7776277 TI - A prospective audit of knee arthroscopy: a study of the accuracy of clinical diagnosis and therapeutic value of 325 knee arthroscopies. AB - A prospective audit of 321 patients (325 knees) placed on the waiting list for arthroscopy revealed an accuracy of the preoperative diagnosis of 57%. The accuracy of consultants was 71% and the other grades of staff was 49%. The operation treated a pathological lesion and was considered to be therapeutic in 154 knees (47%); an operation was more likely to be therapeutic when the preoperative diagnosis was correct (132 knees) than when the diagnosis was incorrect (22 knees). Attention to establishing an accurate preoperative diagnosis and close supervision of the waiting lists by consultants will reduce the number of non-therapeutic arthroscopies. PMID- 7776279 TI - Lap seat-belts: still trouble after all these years. AB - A series of three cases of severe injury caused by involvement in an accident while wearing lap seat-belts is presented. More than 30 years after the term 'seat-belt syndrome' was coined, attention still requires to be drawn to the likely combination of severe spinal and intra-abdominal injuries in such patients. PMID- 7776280 TI - Rembrandt and medicine. PMID- 7776281 TI - Neonatal surgery. AB - Advances in the sophistication of operative and anaesthetic techniques and progress in pre- and postoperative care have contributed to the improved survival of infants undergoing surgery in the neonatal period. Neonatal surgery must be concentrated in designated regional centres where expertise of the full range of paediatric specialties is available to promote research and development of the specialty and to train future generations of paediatric surgeons. PMID- 7776282 TI - Results of 3 cm excision margin for melanoma of the scalp. AB - Local recurrence and survival were evaluated in 19 patients with melanoma of the scalp after conservative local treatment using a standard protocol of 3 cm excision margins and split skin grafting. Sixteen men and three women had a mean age of 46 years. 12 presented with stage I disease, one with stage II, five with stage III, and one with stage IV disease. Nodular melanoma was present in 16 patients. 17 patients had either Clark level IV or V lesions and mean Breslow depth was 3.4 mm (range 0.9-25). Local recurrence occurred in only one patient who had an excision biopsy performed. Six of 12 patients with stage I disease developed regional adenopathy and only 2 are alive after therapeutic block dissection. All patients with stage III and stage IV disease have died. Excision using 3 cm margin is adequate to control local disease. Scalp melanoma is a specific anatomical subsite associated with a high incidence of regional disease and has a poor prognosis. This high risk group of patients may benefit from elective lymph node dissection. PMID- 7776283 TI - Assessment of a specimen mount for biopsy of impalpable breast lesions. AB - Biopsy of the impalpable breast lesion is an increasing part of the surgical workload as a result of the National Breast Cancer Screening Programme. A specimen mount card has been described to orientate such specimens in three dimensions prior to radiological and pathological examination. Experience with 243 biopsies in this unit has shown it to be a useful aid in determining completeness of excision. It may also be used as a guide to further surgery when excision is incomplete and breast conservation is the treatment option of choice. PMID- 7776284 TI - A multivariate analysis of childhood abdominal pain in Trinidad. AB - This is a multivariate analysis of the data recorded in assessing 1158 consecutive admissions presenting to a children's surgical ward with acute abdominal pain. There were 56 binary variables available for entry into the analysis. A statistical software package was used to perform a stepwise discriminant analysis on the data. The program selected 18 variables as having discriminating power in assigning patients to the six diagnostic groups. In order of discriminating power these were, mainly, a positive urine culture, the bowel history, the findings on rectal examination, the location of abdominal tenderness, the presence of a mass, and the white cell count. Lesser discriminating potential was assigned to the presence of dehydration; fluid levels on erect abdominal films, a rise in temperature, an increased pulse rate, the presence of urinary symptoms, and the general appearance of the child. Use of these data led to an overall correct classification of 80.7% of cases. It is concluded that these variables should be included in the assessment of children with acute abdominal pain. PMID- 7776285 TI - Preventive behaviors as correlates of periodontal health status. AB - OBJECTIVES: This investigation examined current practices of brushing, flossing, and periodic dental visits and their association with periodontal health status. METHODS: Data were collected using face-to-face interviews and 40-minute in-home dental examinations with a probability sample of adults 18 years of age or older, having at least one tooth, and living in housing units in the Detroit tricounty area. Complete examinations were performed on 319 individuals. RESULTS: On average, subjects reported brushing their teeth about twice a day. About one third of the population reported flossing at least once a day. Loss of periodontal attachment was related to frequency of brushing while subjects who exhibited acceptable flossing ability had less plaque and calculus, shallower pocket depths, and less attachment loss. Subjects reporting a periodic dental visit at least once a year had less plaque, gingivitis, and calculus than subjects reporting less frequent visits. In regression analyses, brushing thoroughness, flossing ability and frequency, and dental visit frequency were predictors of lower plaque, gingivitis, and calculus scores. In turn, these scores were predictors of shallower pocket depths and less attachment loss. CONCLUSIONS: Brushing, flossing, and periodic dental visits were correlated with better periodontal health. The behaviors appeared to be indirectly related to pocket depth and attachment loss through their associations with plaque, gingivitis, and calculus levels. PMID- 7776286 TI - Differences in judgments of persuasive argument quality by three population groups in Iowa. AB - OBJECTIVES: This study describes a method for studying the perceived persuasiveness of rationales for adopting preventive health behaviors. METHODS: Using the Elaboration Likelihood Model, we surveyed 156 individuals as to the level of persuasiveness that each of several categories of reason presented in adopting target "prevention" behaviors such as eliminating the use of smokeless tobacco or seeking regular dental care. RESULTS: Significant differences between what the public reported as persuasive reasons and those selected by future dental practitioners were found. Patients saw potential cost savings, elimination of future pain, and being told by an authority person to adopt a behavior as highly persuasive reasons to adopt a target behavior. Nonwhite patients gave significantly higher scores than did white patients to arguments centering on social/aesthetic appeal. On the negative side, episodic care seekers felt significantly more strongly than regular care seekers that their practicing dental prevention activities (e.g., regular checkups, brushing, and flossing) benefited someone other than themselves (dental profession and dental manufacturers). CONCLUSIONS: Results of this study suggest that one way to improve persuasive public health preventive messages is to consider whether the fundamental arguments on which preventive health campaigns are built have broad patient appeal. PMID- 7776287 TI - Relationships of personality traits and stress to gingival status or soft-tissue oral pathology: an exploratory study. AB - OBJECTIVES: The purpose of this study was to examine the relationships of personality traits and stress with gingival inflammation and with soft-tissue oral pathology. METHODS: Personality traits of psychoticism (P), extroversion and introversion (E), and neuroticism (N) were measured with Eysenck's personality questionnaire (EPQ). Stress was measured with a modified organizational and individual assessment survey (OIAS) developed by Hendrix. Military recruits from Ft. Leonard Wood, Missouri, were examined for soft-tissue oral pathology and gingival status at weeks one (n = 241) and six (n = 61) of basic combat training (BCT). The EPQ and OIAS were administered to 217 recruits during week six of BCT. A discriminant analysis was used to determine correlations among study variables. RESULTS: Significant correlations (P < .05) were found between personality traits and various measures of tolerance of stress. Little variance was found between groups originally presenting with or without disease. Only physical stress (P < .005) was shown to affect soft-tissue pathology, while gingival inflammation correlated significantly to E scores (P < .02), tolerance to change (P < .02), and anxiety (P < .05). CONCLUSIONS: Data support a possible relationship among certain personality traits, stress variables, and gingival inflammation or soft tissue pathology in recruits with extreme personality characteristics or perception of high physical stress levels in basic combat training. PMID- 7776288 TI - Considerations in establishing a dental program for the homeless. AB - The homeless are a diverse group who present the dental profession with a number of difficult challenges in the delivery of oral health services. Utilization of dental services by the homeless is low when provided in traditional settings and access is limited. The purpose of this case study is to review program planning issues focusing on the unique aspects of establishing dental programs for the shelter-based homeless. This paper is based on experiences in developing a dental program for homeless persons in Boston. The establishment of a portable dental program in 1988 for persons residing in shelters in the greater Boston area involved many administrative and clinical considerations. These factors included determination of needs and barriers to dental care, resource identification and development, program planning and implementation, evaluation, and the development of constituency support. The diversity of the homeless population in combination with the variation of space and medical resources at different shelter sites dictates flexibility in the development of programs to address the oral health needs of the homeless. PMID- 7776289 TI - A new era for community water fluoridation? Achievements after one-half century and challenges ahead. PMID- 7776290 TI - Dental caries in homeless adults in Boston. AB - OBJECTIVES: Information about the oral health status of the homeless is limited. The purpose of this study is to characterize the dental caries status among users of a dental treatment and referral program at homeless shelters in Boston, MA. METHODS: Persons attending the program during a one-year period were assessed for evidence of dental caries experience by a single examiner. DMFT counts were abstracted from patient records. RESULTS: The population examined (n = 73) was 66 percent male with a mean age of 36 years. The racial composition was 51 percent African-American, 34 percent Caucasian, and 14 percent Hispanic. The 70 dentate people examined had a mean DFT of 11.1 (SD = 6.1). The mean percent of DFT that was DT per person was 55.7 percent. Untreated caries was detected in 91.4 percent of those examined. CONCLUSIONS: These findings show evidence of previous dental services utilization by these homeless individuals, but demonstrate a high need for preventive and restorative dental therapy. PMID- 7776291 TI - Fluoride--how much of a good thing? Introduction to the symposium. AB - January 25, 1995, is the 50th anniversary of the first controlled addition of fluoride to a public water supply. Those 50 years have seen extraordinary advances in oral health and consequent quality of life, for which fluoride use is generally considered the primary reason. More extensive exposure to fluoride in the modern era, however, has led to both a continuing decline in caries experience and an increased prevalence of dental fluorosis in children. At the other end of life, fluoride's role in bone strength among older people is not well defined. This symposium examines several aspects of fluoride use in the United States today, and has the purpose of helping to define the balance between maximizing the benefits of fluoride while minimizing its undesirable side effects. PMID- 7776292 TI - Sources of fluoride intake in children. AB - Wide variations in fluoride intake among children make estimating fluoride intake difficult. This paper discusses the various sources of fluoride intake among children, beginning with a review of the fluoride concentrations of water and other beverages, foods, and therapeutic fluoride products. A review of previous studies' estimates of fluoride intake from diet, dentifrice, fluoride supplements, fluoride mouthrinses, and gels, as well as total fluoride intake also is presented. Then, estimates of fluoride intake among young children of different age groups are summarized, and examples demonstrating the high level of variability of fluoride intake, both from individual sources and in total, are presented. Lastly, this paper discusses the implications of our current level of knowledge of children's fluoride intake, and presents recommendations for the use of fluoride for children in light of this current knowledge. The major recommendations are that: (1) the fluoride content of foods and beverages, particularly infant formulas and water used in their reconstitution, should continue to be monitored closely in an effort to limit excessive fluoride intake; (2) ingestion of fluoride from dentifrice by young children should be controlled, and the use of only small quantities of dentifrice by young children should be emphasized; and (3) dietary fluoride supplements should be considered a targeted preventive regimen only for those children at higher risk for dental caries and with low levels of ingested fluoride from other sources. PMID- 7776294 TI - Commentary on and recommendations for the proper uses of fluoride. AB - Fluorosis has been associated with the fluoride concentration of drinking water, use of dietary fluoride supplements, early use of dentifrices, and prolonged use of infant formula. The literature, however, does not show associations between fluorosis and use of fluoride mouthrinses, professionally applied fluorides, bottled waters, carbonated beverages, and juices. It is unwise to issue laundry lists of items that may be implicated as problem-causing when, in fact, they may not be. Although usually classified without fluorosis, children in Dean's "questionable" category would be classified with the condition if the TFI or TSIF were used. Accordingly, Dean, in 1942, really reported only 52.8 percent of children without fluorosis in Kewanee, a community with 0.9 ppm fluoride in drinking water. Because the morbidity and sequelae of dental caries have declined, undue emphasis has been placed recently on the risks of using fluoride rather than on its profound beneficial effects. Although of paramount importance, conclusions cannot be drawn on whether fluoride protects against, contributes to, or has no effect on bone fractures or is valuable in treating osteoporosis. Careful thought is required before making recommendations that may reduce health benefits because of unfounded concerns about perceived risks. There should be greater regulation of extraneous fluoride sources, rather than reliance on educational efforts or recommendations to eliminate use of highly effective preventive regimens. PMID- 7776293 TI - Fluoride and bone health. AB - This paper reviews some of the studies related to the effect of fluoride on the skeletal system of humans and outlines the knowns and unknowns of fluoride and bone health. Current research indicates that, in large enough doses, fluoride stimulates bone formation by osteoblastic stimulation, increases bone formation earlier and to a larger extent in trabecular bone compared to cortical bone, and increases spinal bone density. There is controversy, however, concerning the efficacy of fluoride as a therapeutic agent in the treatment of osteoporosis. Some clinical studies have found a reduction in vertebral fracture rates while others have not. To date, only ecologic studies have been conducted on the association between water fluoridation and hip fractures. The inability of ecologic studies to control for confounding variables makes their interpretation difficult. Based on the literature presented, it is concluded that there are more unknowns than knowns in terms of fluoride's effect on bone, osteoporosis, and fractures. One of the major unknowns in the relationship between fluoride and bone health is dose and duration. Two studies are underway that attempt to describe the dose-response relationship between waterborne fluoride and osteoporosis. These studies will be completed in the near future and their results, while providing new insight into fluoride's effects on bone, will by no means answer all the questions raised on this issue. PMID- 7776295 TI - The weight of scientific evidence: introducing the brief communication for the JPHD. PMID- 7776297 TI - Colposcopically directed biopsy and loop excision of the transformation zone. Comparison of histologic findings. AB - We performed a retrospective comparison between the findings from colposcopically directed biopsies and those from loop excision of the transformation zone (LETZ) specimens. The correlation was satisfactory. When a low grade squamous intraepithelial lesion (SIL) was predicted on a cytologic smear and biopsy specimen, no cases of invasive carcinoma were found. In two (0.8%) cases in which a high grade SIL was predicted on the cervical smear and biopsy, microinvasive carcinoma was found in the LETZ specimen. PMID- 7776296 TI - Oral health: an essential service for the homeless. PMID- 7776298 TI - Development of wound infection or separation after cesarean delivery. Prospective evaluation of 2,431 cases. AB - Wound infections are a common surgical complication, often requiring a prolonged hospital stay and leading to increased costs. Over a one-year period, 2,431 patients were followed after cesarean delivery with prompt evaluation and culture of all suspicious wounds. Seventy subjects (2.8%) developed confirmed wound infection, and 42 (1.7%) developed noninfected open surgical wounds. Seven (0.3%) fascial dehiscences were diagnosed, requiring surgical repair. Forty of 63 (64%) infected wounds had positive bacterial cultures, with Staphylococcus epidermidis (29%), Enterococcus faecalis (17%), Staphylococcus aureus (17%), Escherichia coli (11%) and Proteus mirabilis (10%) the most frequent isolates. Only 7 of 42 (17%) noninfected wounds had positive cultures, with only S aureus, S epidermidis and Corynebacterium species isolated. Ninety-five percent of the noninfected wounds had blood or serous collections present. Rupture of membranes lasting longer than six hours, emergency cesarean delivery and morbid obesity were associated with a statistically increased likelihood of the development of infected wounds. Emergency cesarean delivery and morbid obesity, but not prolonged rupture of membranes, were associated with an increased likelihood of the development of noninfected wounds. Therefore, it appears that at least two mechanisms are responsible for the development of postcesarean open wounds: (1) increased amniotic fluid and wound colonization due to prolonged rupture of membranes, resulting in a wound infection containing one or more bacterial species derived from the cervicovaginal flora, and (2) increased exogenous bacterial contamination and flora consistent with skin species or breaks in sterile technique, often accompanying difficult or emergency surgery. PMID- 7776299 TI - Mass antimicrobial treatment in pregnancy. A randomized, placebo-controlled trial in a population with high rates of sexually transmitted diseases. AB - Sexually transmitted diseases (STDs) are highly prevalent in pregnant women in many developing countries and have been associated with poor obstetric outcomes. Case detection and treatment of STDs in women is problematic and expensive, underscoring the need for other strategies. To explore the potential benefits of routine antimicrobial therapy on pregnancy outcome, we carried out a randomized, double-blind, clinical trial in one of the antenatal clinics in Nairobi, Kenya. Four hundred pregnant women between 28 and 32 weeks' gestation were given a single dose of 250 mg ceftriaxone intramuscularly or a placebo. There was a significant difference between ceftriaxone and placebo-treated women in infant birth weight (3,209 versus 3,056 g, P = .01). In addition, there was a trend toward lower rates of birth weight < 2,500 g (4.0% versus 9.2%, P = .08) and postpartum endometritis (3.8% versus 10.4%, P = .05) in the intervention than in the placebo group. Neisseria gonorrhoeae was isolated from the cervixes of postpartum women in 1.8% of the intervention group as compared to 4.2% of the control group. These data suggest a beneficial effect of antimicrobial prophylaxis on pregnancy outcome. Larger studies should be carried out to examine the public health impact of this intervention. PMID- 7776300 TI - Transvestibular retropubic bladder neck suspension. A pilot study. AB - A pilot study was conducted assessing the operative feasibility, complications and results of a retropubic bladder neck suspension performed through a transvestibular approach. This study extended from July 1, 1990, to June 30, 1991, and included patients who planned to undergo primary surgical correction of stress urinary incontinence. Through a transvestibular incision, a bladder neck suspension was performed by suturing the adjacent area of the vagina to the back of the pubic symphysis or the puborectalis muscle near the pubic bone. Ten women were entered into the study. There was one notable complication, a hematoma in the space of Retzius. One patient described worsening of her incontinence and underwent a Marshall-Marchetti-Krantz procedure three months postoperatively. The mean follow-up for the remaining nine patients was 27 months (range, 13-31). At this writing, 6 patients were completely continent, 1 was improved, and 2 had some degree of bladder instability with associated incontinence. Overall, the transvestibular procedure was thought to be technically difficult. Based on very limited data, the results of the study have discouraged our continued use of this procedure. The transvestibular approach may be applicable occasionally on selected patients. PMID- 7776301 TI - Off-label drug prescribing on a state university obstetric service. AB - Off-label drug use occurs when physicians prescribe a drug recommended for indications other than those listed on the prescription labeling. The purpose of the present investigation was to describe patterns of off-label drug use during pregnancy, including the types of drugs and their timing of use. All study pregnancies had to receive prenatal care at our state university clinics before 14 weeks' gestation and deliver at our institution during a five-month period. Prenatal records were reviewed, and subjects were interviewed after delivery. A total of 165 (22.6%) of the 731 eligible subjects took > or = 1 (average 1.7, 95% confidence interval 1.3-3.8) drugs for off-label indications. Nearly all drugs were taken for a short term during the third trimester. The primary purposes were to avoid an obstetric complication (premature labor and delivery, preeclampsia/eclampsia) or improve the capacity for eventual postnatal adaptation. Despite discussions with patients, on no occasion was it recorded on the chart that the patient was informed that the drug was recommended for an off label indication. Results from this study should help drug manufacturers, insurance companies and federal regulatory agencies understand the common use of recommending certain drugs for off-label indications during pregnancy. PMID- 7776302 TI - Uterine artery ligation in the control of postcesarean hemorrhage. AB - The technique is described for devascularizing the post-cesarean section uterus with bilateral mass ligation of the ascending branches of the uterine arteries and veins. This 30-year clinical experience with 265 patients includes the results and complications. Ten patients required additional therapy. The effectiveness of this technique makes it a reasonable alternative to hypogastric artery ligation and reduces the need for hysterectomy. PMID- 7776303 TI - Palpable uterine artery pulsation as a clinical indicator of early pregnancy. AB - The objective of this study was to determine if palpable uterine artery pulsation is a reliable clinical indicator of pregnancy at less than six weeks' gestation. A preliminary, nonblind study involved 299 women. Of 31 women who were at less than six weeks' gestation, 24 had definite uterine artery pulsations, and 7 did not. Of 268 nonpregnant women, 256 did not have pulsation, while 12 did (P < .001). Because other clinical parameters could bias the interpretation of uterine artery pulsation, a second, blind study was undertaken. During it, 155 patients underwent bimanual examination only, and no other clinical information was available to the examiner. Of 25 women at less than six weeks' gestation, 19 had definite uterine artery pulsation, while 6 did not. Of 130 nonpregnant patients, 121 did not have uterine artery pulsation, while 9 did (P < .001). Palpable uterine artery pulsation seems to be associated with early pregnancy, and physicians should add evaluation of pulsation to their clinical armamentarium. PMID- 7776304 TI - Cocaine use in pregnancy and the risk of intraamniotic infection. AB - A retrospective, case-control study was performed to determine whether pregnant women using cocaine had an increase in maternal infectious morbidity. Seventy-six women with urine drug screens positive for cocaine on admission to the labor and delivery unit were compared to 134 women who had negative urine drug screens. Patients were matched for risk factors associated with the development of intraamniotic infection and endometritis, such as parity, length of labor and length of membrane rupture. There was no significant difference in the incidence of intraamniotic infection or endometritis between the two groups. Thus, cocaine does not appear to increase the risk of peripartum infectious morbidity after controlling for well-established risk factors. PMID- 7776305 TI - Ionized serum magnesium and potassium levels in pregnant women with preeclampsia and eclampsia. AB - A prospective, cross-sectional study was performed to determine whether patients with preeclampsia or eclampsia had difficult serum levels or fractions of the active, ionized form of magnesium (IMg2+) as compared to normal, pregnant women. Using a novel ion selective electrode, we determined the IMg2+ levels and fractions as well as ionized calcium, sodium and potassium (K) in venous serum drawn on admission from 33 normal, pregnant women; 12 women with preeclampsia; and 2 women with postpartum eclampsia. Levels in 42 nonpregnant, age-matched, healthy women were also measured. We found that in normal pregnancy, levels and fractions of IMg2+ were significantly decreased as compared to levels and fractions in nonpregnant women (0.48 +/- 0.01 [SE] versus 0.60 +/- 0.005 mmol/L, and 63.2 +/- 1.0% versus 71.6 +/- 0.6%; P < .001 for both), but the levels and fractions in preeclamptics (0.48 +/- 0.01 mmol/L and 64.2 +/- 1.7%) were not significantly different (P > .05) from those in normal, pregnant women. Similarly, the levels and fractions of IMg2+ in the two eclamptic patients were within the ranges of normal and preeclamptic pregnancies. When the other cations were analyzed, a highly significant elevation (P < .001) in the mean K+ level and the K+/IMg2+ ratio in the preeclamptic patients was noted. Thus, it appears that serum IMg2+ levels are maintained in preeclampsia and eclampsia, but disturbances in K homeostasis and in the interrelationships between K and IMg2+ may occur. PMID- 7776307 TI - Laparoscopic resection of a noncommunicating rudimentary uterine horn. A case report. AB - Patients who have a unicornuate uterus with a noncommunicating rudimentary horn that contains an endometrial cavity are at risk for endometriosis and obstetric complications. As in this case, resection of the rudimentary horn can be performed laparoscopically without increased risk to the patient and with some potential benefit. PMID- 7776306 TI - Serum parathyroid hormone-related protein levels during lactation. AB - We measured parathyroid hormone-related protein (PTHrP) in the serum of 15 healthy women within three days of beginning breast-feeding and within one hour of completing nursing. A sensitive immunoradiometric assay that measures N terminal PTHrP containing at least the first 74 amino acids was used. We found normal PTHrP values in all patients. Values one day before and two days after delivery in a hypoparathyroid woman who chose not to breast-feed were also normal. Since N-terminal PTHrP fragments of 1-36 amino acids or more are biologically active, we believe additional studies using sensitive PTHrP assays that measure smaller fragments and investigations performed under other conditions of breast-feeding are necessary before concluding that PTHrP does not have a role in calcium homeostasis in nursing mothers. Furthermore, additional studies in hypoparathyroid nursing mothers should be performed. PMID- 7776308 TI - Vesicouterine fistula after cesarean section. A case report. AB - A 27-year-old woman, gravida 3, para 2002, underwent repeat cesarean section and inadvertent cystotomy, with subsequent development of a vesicouterine fistula. The fistula did not resolve with prolonged bladder catheterization and required total abdominal hysterectomy with resection of the fistula tract and primary closure for definitive treatment. PMID- 7776309 TI - Tuboovarian abscess associated with Candida glabrata in a woman with an intrauterine device. A case report. AB - Candidal infection has been associated extensively with serious infections. Its role in genital tract infections has consisted largely of vulvovaginitis, with serious upper genital tract infection a rarity. A 47-year-old woman with an intrauterine device had Candida glabrata in a large tuboovarian abscess and recovered only after removal of the abscess and treatment with amphotericin B. PMID- 7776310 TI - Sciatic nerve endometriosis treated with a gonadotropin releasing hormone agonist. A case report. AB - Sciatic nerve endometriosis was previously treated primarily with surgery. Most commonly hysterectomy and bilateral salpingo-oophorectomy have been used; however, two reports also describe successful conservative surgery with resection of the endometriosis from the sciatic nerve. Only one case of sciatic nerve endometriosis has been reported to have responded to medical management. This report details the rapid and complete resolution of sciatica secondary to endometriosis after medical treatment with the gonadotropin releasing hormone analog leuprolide acetate for depot suspension. PMID- 7776311 TI - Leiomyoma of the female urethra. A report of two cases. AB - Leiomyoma of the female urethra is rare; only 34 cases have been reported in the medical literature in English. We report two additional cases in which hormonal factors appeared to play an important role. PMID- 7776312 TI - Extrapulmonary tuberculosis as a cause of unexplained postpartum fever. A case report. PMID- 7776313 TI - Garrulitas vulvae. A report of six cases. PMID- 7776314 TI - Pregnancy after endometrial ablation. A case report. AB - Pregnancy is a known but rare complication of endometrial ablation. In this case it ended in spontaneous abortion, but full-term pregnancy has been reported. PMID- 7776316 TI - Laparoscopic cholecystectomy in pregnancy. A case report. AB - Laparoscopic cholecystectomy was performed on a pregnant woman at 18 weeks of gestation without complications. Considering the risk/benefit ratio, laparoscopic cholecystectomy in pregnant women is preferable to conventional cholecystectomy. PMID- 7776315 TI - Pregnancy complicated by the Klippel-Trenaunay syndrome. A case report. AB - A primigravida with the Klippel-Trenaunay syndrome was admitted to the hospital at 34 weeks' gestation with a complaint of right calf pain. Superficial thrombophlebitis was diagnosed, and she was treated with compresses and analgesia. Speculum examination failed to reveal the presence of lower genitourinary tract arteriovenous malformations. Color flow mapping of the uterus did not identify any arteriovenous malformations. The patient delivered vaginally at term, and the postpartum course was unremarkable. Pregnancies complicated by the Klippel-Trenaunay syndrome are at increased risk of adverse perinatal outcomes, related primarily to the increased risk of hemorrhagic diathesis. The mode of delivery should be considered carefully in an attempt to minimize the risk to both mother and fetus. PMID- 7776317 TI - Conflict of interests: an introduction. AB - In earlier times, clinical researchers published the results of their studies as seemed most appropriate to them. In an increasingly computerized and communicative environment this is no longer satisfactory, since now there are a number of other groups whose interests need to be taken into account. These include patients, medical journals, the Stock Exchange, the media and the law. This supplement arises out of a meeting established to describe the methods used to communicate clinical research results, the timing and the needs of other groups in an attempt to improve understanding and to identify preferred practice. Avoidance by clinical investigators of conflict of interest and accusations of improper practice clearly merit discussion. PMID- 7776318 TI - Pressure on communication of results of clinical research: potential for improper practice. Proceedings of a meeting. London, October 13, 1993. AB - In earlier times, clinical researchers published the results of their studies as seemed most appropriate to them. In an increasingly computerized and communicative environment this is no longer satisfactory, since now there are a number of other groups whose interests need to be taken into account. These include patients, medical journals, the Stock Exchange, the media and the law. This supplement arises out of a meeting established to describe the methods used to communicate clinical research results, the timing and the needs of other groups in an attempt to improve understanding and to identify preferred practice. Avoidance by clinical investigators of conflict of interest and accusations of improper practice clearly merit discussion. PMID- 7776319 TI - Insider dealing rules: legal aspects. PMID- 7776320 TI - Publication of clinical trial results: a clinician's view. PMID- 7776321 TI - Publication of clinical trial results: a clinical investigator's view. PMID- 7776322 TI - Insider dealing rules: a financial analyst's view. PMID- 7776323 TI - Abdominal radiology in cystic fibrosis. PMID- 7776324 TI - Human recombinant DNase in cystic fibrosis. PMID- 7776325 TI - Colonic strictures in cystic fibrosis. PMID- 7776327 TI - Post heart/lung transplantation management. AB - Patients with cystic fibrosis present a challenge to management post transplantation but the results are comparable with those obtained in patients with other conditions. The increasing population of cystic fibrosis patients who have undergone transplantation will require joint management of such patients by cystic fibrosis specialists and pulmonary transplant specialists. The follow-up of patients with cystic fibrosis following pulmonary transplantation potentially affords us an exciting opportunity to study the natural history of this disease as it affects the extra pulmonary organs. PMID- 7776326 TI - Exercise and cystic fibrosis. PMID- 7776330 TI - Dermoid sinus in a Boerboel bitch. PMID- 7776331 TI - Equine viral arteritis in donkeys in South Africa. PMID- 7776329 TI - Abdominal pain in cystic fibrosis. PMID- 7776328 TI - Allergic and invasive aspergillosis. PMID- 7776333 TI - An assessment of the toxicity of parenteral treatment with copper EDTA and copper heptonate in sheep. AB - The toxicity of 2 parenteral copper (Cu) supplements was investigated. Di-sodium copper ethylene diamino tetra acetate (Cu EDTA) and Cu heptonate were administered to sheep (n = 9) by a single subcutaneous injection at a concentration of 0,2, 1 and 2 mg Cu/kg each (Trial 1.) Nine sheep were untreated and served as controls. The same treatments were applied to 2 sheep each (Trial 2) with the addition of 3 mg Cu/kg live body mass as Cu heptonate, and Cu heptonate administered intravenously at rates of 0,2, 0,4 and 0,6 mg Cu/kg live body mass. In Trial 1, 67% of the sheep treated with Cu EDTA at 2 mg Cu/kg live body mass died within 3 to 17 d after treatment, while no mortalities occurred in sheep where Cu heptonate was administered at the same dosage rate and even at 3 mg Cu/kg live body mass (P < or = 0,01). Post-mortem examination suggested acute Cu toxicity in all cases. Liver Cu concentrations were markedly increased (P < or = 0,05) by both supplements in groups of 3 treated sheep slaughtered over a 3 month period compared to control animals. The liver Cu concentrations of sheep that succumbed to Cu toxicity were within the normal range of 100 to 450 mg/kg DM. Results from Trial 2 suggested that the 2 sheep treated with 2 mg Cu/kg live body mass as Cu EDTA, experienced a haemolytic crisis between 5 and 11 d after treatment, resulting in the death of one of these sheep. The haemolytic crisis was characterised by a severe decrease in haemoglobin concentration and haematocrit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776334 TI - Production responses of sheep supplemented with copper, cobalt and selenium on kikuyu ryegrass pastures. AB - The copper (Cu) and selenium (Se) status of SA Mutton Merino ewes grazing kikuyu ryegrass pastures was investigated by analysing blood and liver samples. The response of ewes to oral supplementation with Cu, Cobalt (Co) and Se as single elements, or in 4 combinations were simultaneously assessed in a 2 x 2 x 2 factorial experiment. Pastures grazed were low in Cu (less than 5 mg Cu/kg DM) except for the summer months, while pasture Se concentrations remained at concentrations less than 0,03 mg Se/kg DM for almost the entire period. Plasma Cu concentrations remained in excess of 80 micrograms/dl until pasture Cu concentrations decreased below 5 mg/kg DM. Blood Se concentrations generally reflected liver Se concentrations. Supplementation of ewes with 5 g Cu oxide needles (Embamin Copper LA, Rhone Poulenc) markedly increased (P < or = 0,01) hepatic Cu and plasma Cu concentrations. The monthly drenching of ewes with 5 mg Se as sodium selenite elevated blood Se concentrations to normal levels in excess of 100 ng/ml while ewes not supplemented with Se had blood Se concentrations indicative of a deficiency (50-100 ng/ml). Supplementation of ewes with Cu and Se elevated (P < or = 0,05) concentrations of these trace elements in the plasma and blood of their progeny. Supplementation of ewes with Cu and Se resulted in respective improvements (P < or = 0,05) of 5,3 and 4,8% in live mass during lactation, compared to contemporaries which did not receive either Cu or Se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776332 TI - Factors which affect blood variables of slaughtered cattle. AB - Blood was obtained at an abattoir from 4 groups of cattle. The first group was slaughtered in a conventional way, the second and third were subjected to shechita slaughter with or without the application of the captive bolt immediately after the cutting of the throat, and the fourth group of cattle was subjected to a period of recumbency prior to conventional slaughter. Blood samples were analysed for concentrations of catecholamines, cortisol, glucose, lactate and total lipids. The haematocrit and osmolarity was also determined. There were no major differences in the blood variables of cattle subjected to conventional slaughter and those of cattle which had been subjected to a period of recumbency prior to conventional slaughter. Plasma catecholamine concentrations in cattle subjected to shechita slaughter without the application of a stun, were significantly elevated when compared to any of the other groups. It was concluded that postural changes have very little effect on the blood variables, but that the application of a stun after the throat has been cut in shechita slaughter abolishes the increases in blood variables associated with shechita in the absence of stunning. PMID- 7776335 TI - The effectiveness of using supplementary zinc and molybdenum to reduce the copper content in the liver of hypercuprotic sheep. AB - Two trials were conducted to evaluate the effectiveness of different methods of reducing the liver copper (Cu) concentration of sheep whose livers had been loaded with Cu, in order to protect the sheep from Cu toxicity, after dietary Cu had been withdrawn. In the first trial 0, 75, 150 and 300 mg zinc (Zn) kg-1 feed were added to a basic diet low in Cu and fed to hypercuprotic sheep (n = 32) for 88 d. At the end of the trial, liver Cu concentrations (c 800 mg Cu kg-1 DM) in all 4 treatments did not differ significantly from the Cu concentrations of the liver biopsy samples taken at the onset of the trial. From other measurements taken, none of the sheep appeared to be close to the haemolytic phase of chronic Cu toxicity. In the second trial, lasting 79 d, 40 hypercuprotic sheep were allocated to 4 treatments, viz. a control, a group receiving a parenteral treatment of Zn, amounting to approximately 7 mg Zn d-1 and 2 further groups receiving molybdenum (Mo) (15 and 30 mg Mo sheep-1 d-1), added to the basic diet high in sulphur (4,06 g kg-1 DM). The parenteral Zn treatment did not change liver Cu concentrations. The 15 mg and 30 mg Mo treatments reduced the Cu in the livers significantly by 24% and 42% respectively. It is suggested that both oral and parenteral Zn supplementation are ineffective in reducing liver Cu concentration once dietary Cu has been withdrawn from the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776336 TI - Serological relationship between a donkey alphaherpesvirus (isolate M7/91) and equid herpesvirus type 1 and 4. AB - Rabbit hyperimmune serum prepared against a donkey alphaherpesvirus isolate (M7/91), and against EHV-1 and EHV-4 was used to characterise the antigenic relationship between these 3 viruses. Serum from immunised rabbits was always more specific for homologous virus and showed different cross reactivity for heterologous virus. It was concluded that the immunologic relationship between the M7/91 isolate and EHV-1, was closer than that between this isolate and EHV-4. A serological survey of donkeys (n = 116) and horses (n = 57) revealed evidence of the presence of neutralising antibody to M7/91 in their sera. The titres of antibody to M7/91 in donkeys, ranged from 1:32-1 > or = 256 and was significantly higher than antibody titres to EHV-1 and EHV-4, while in horses, titres were lower but comparable to equine herpesvirus 1 and 4. PMID- 7776337 TI - Demographics of companion animals in South Africa. AB - A survey conducted in 1992, using a standardised, stratified sample was used to determine companion animal numbers in South Africa as a single geographical entity. The results indicated that there were 3.93 million dogs, 0.97 million cats, 0.98 million birds, 0.22 million other companion animals and 0.1 million horses in South African households. Thirty-seven per cent of households keeping companion animals, kept dogs; cats (13.4%); birds (4.8%); other companion animals (1.1%) and horses (2%). These results may provide information about possible markets in terms of numbers of species kept. PMID- 7776338 TI - Congenital skeletal malformations in Holstein calves associated with putative manganese deficiency. AB - Holstein calves (n = 47) with a dwarf-like appearance, joint laxity, superior brachygnathism and domed foreheads were born to heifers on natural grazing on the same farm. Six calves, between one week and 3 months of age, were euthanased. Marginally low concentrations of manganese were found in the livers, while high strontium concentrations were confirmed in soil, plants and grass specimens from the pasture, as well as in the bone ash of the ribs of 2 calves. Microscopical lesions in growth plates included irregularly aligned and shorter columns of chondrocytes and a reduction in width of the zone of hypertrophy when compared to a normal calf. This syndrome closely resembled a previously described chondrodystrophy in neonatal calves, attributed to a maternal manganese deficiency. Seepage from sea water evaporation pans on an adjacent farm was believed to have resulted in leaching of manganese from the soil and to be the source of the high levels of strontium. The cause of the skeletal defects is believed to be maternal manganese deficiency, complicated by an unknown factor. PMID- 7776339 TI - Advanced tuberculosis in an African buffalo (Syncerus caffer Sparrman). AB - A necropsy conducted on an emaciated 8-year-old female African buffalo (Syncerus caffer) in the Kruger National Park, revealed gross pathological changes compatible with generalised bovine tuberculosis. Macroscopic lesions in the lungs and associated lymph nodes were of a caseous necrotic nature with liquefied foci. Mycobacterium bovis was cultured from pulmonary lesions. The distribution and the characteristics of the lesions are described and the conclusion is made that the initial route of infection was aerogenous with secondary bacterial metastasis to the intestine. It would also appear that the spread of infection within the animal was extremely rapid. The conjecture is made that due to the cavernous state of the pulmonary lesions, the animal was probably highly infective at the time of death. Environmental factors that may have had an influence on the pathogenesis of the disease are seasonal rainfall fluctuations, extreme temperature variations and harsh ultra-violet exposure. PMID- 7776340 TI - Suspected chronic fluorosis in a sheep flock. AB - An estimated average daily intake of 107 g of a lick containing 3.4% of a commercial non-defluorinated rockphosphate, which has an average fluoride content of 2.5% m/m, caused an outbreak of suspected chronic fluorosis in a Dohne Merino sheep flock in the eastern Cape. Thirty seven per cent of the commercial 4-tooth animals were affected, whereas only 17% of the stud component of the same age group, which were in a better nutritional condition, showed clinical signs of fluorosis. Twenty per cent and 33.3% of the 6-tooth wethers and ewes respectively, were affected. Younger sheep and sheep in a relatively poor body condition, were more affected than older sheep and those in a relatively better condition. Non-defluorinated non-registered mineral sources should not be included in supplementary rations for sheep. PMID- 7776341 TI - A Dutch report on the ethics of neonatal care. AB - The Dutch Paediatric Association reports consensus among its members regarding the necessity to take the future quality of life into account when reaching decisions regarding the continuation or dis-continuation of life-prolonging treatment. The paramount importance of the discussion with the parents is stressed. Dissension exists regarding active euthanasia in the newborn, both opinions being respected. If dissension exists within the profession parents should be informed and if necessary referred to a doctor who shares their moral views. PMID- 7776343 TI - Ultimate justification: Wittgenstein and medical ethics. AB - Decisions must be justified. In medical ethics various grounds are given to justify decisions, but ultimate justification seems illusory and little considered. The philosopher Wittgenstein discusses the problem of ultimate justification in the context of general philosophy. His comments, nevertheless, are pertinent to ethics. From a discussion of Wittgensteinian notions, such as 'bedrock', the idea that 'ultimate' justification is grounded in human nature as such is derived. This discussion is relevant to medical ethics in at least five ways: it shows generally what type of certainty there is in practical ethics; it seems to imply some objective foundation to our ethical judgements; it squares with our experience of making ethical decisions; it shows something of the nature of moral arguments; and, finally, it has implications for teaching medicine and ethics. PMID- 7776342 TI - Can there be an ethics of care? AB - There is a growing body of writing, for instance from the nursing profession, espousing an approach to ethics based on care. I suggest that this approach is hopelessly vague and that the vagueness is due to an inadequate analysis of the concept of care. An analysis of 'care' and related terms suggests that care is morally neutral. Caring is not good in itself, but only when it is for the right things and expressed in the right way. 'Caring' ethics assumes wrongly that caring is good, thus it can tell us neither what constitutes those right things, nor what constitutes the right way. PMID- 7776344 TI - Twenty years of the JME--reflections. Journal of Medical Ethics. PMID- 7776345 TI - Enhancing humanistic skills: an experiential approach to learning about ethical issues in health care. AB - An outstanding feature of the study of nursing ethics is that it raises questions concerning moral virtue, conscience, consistency and character. A considerable section of the literature is devoted to ideas of how best to teach ethics to health professionals. It has been shown that when faced with ethical dilemmas nurses tended to rely on intuition and instinct to resolve them, with little systematic analysis to help the process. Nurses who have been in practice for a number of years may experience particular difficulties in resolving ethical dilemmas, for although they may be able easily to identify ethical problems they may feel powerless to behave appropriately through lack of theoretical background and/or confidence in participating in informed debate. An educational programme was designed to meet the needs of mature registered nurses who were undertaking a post-qualification part-time honours degree in nursing studies. A variety of teaching methods were employed in teaching the nurses. These included discussion, student-led seminars, structured debate and role play. A session which dealt with sudden death and organ donation is described in some detail. Because the topic involved communication between professionals and patients and/or relatives and was linked with ethics, role play was used to explore the dynamics in these areas. The participants were invited to act out the situation as they felt it might occur. Role play highlighted the stress and shock attached to such an experience. Before working through the dynamics of a situation the nurses were conscious of being part of decision-making 'in the cold' and 'in isolation'. As a result of the experiential learning they felt more able to reflect analytically and to participate in discussions in an informed and articulate way. PMID- 7776346 TI - Peter Singer and 'lives not worth living'--comments on a flawed argument from analogy. AB - The Australian bioethicist Peter Singer has presented an intriguing argument for the opinion that it is quite proper (morally) to deem the lives of certain individuals not worth living and so to kill them. The argument is based on the alleged analogy between the ordinary clinical judgement that a life with a broken leg is worse than a life with an intact leg (other things being equal), and that the broken leg therefore ought to be mended, on the one hand, and the judgement that the lives of some individuals, for example, severely disabled infants, are not worth living and therefore ought to be terminated, on the other. In the present article it is argued that Singer's argument is flawed, intellectually and/or ethically. PMID- 7776348 TI - What I actually said about medical ethics: a brief response to Toon. AB - It has been said that I am against medical philosophy. This is a misrepresentation of my position. I am against conventional medical ethics teaching as it has to be done in medical schools, but very much in favour of philosophy in medicine. PMID- 7776347 TI - Cardiopulmonary resuscitation in the elderly: patients' and relatives' views. AB - One hundred inpatients on an acute hospital elderly care unit and 43 of their relatives were interviewed shortly before hospital discharge. Eighty per cent of elderly patients and their relatives were aware of cardiopulmonary resuscitation (CPR). Television drama was their main source of information. Patients and relatives overestimated the effectiveness of CPR. Eighty-six per cent of patients were willing to be routinely consulted by doctors about their own CPR status, but relatives were less enthusiastic about routine consultation. Patients' and relatives' views about the appropriateness of CPR did not differ significantly. Seventeen percent of patients did not desire CPR. However, 64 per cent of patients were ultimately willing to follow their doctor's advice about the appropriateness of CPR. The conclusion reached is that mentally competent, elderly patients but not their relatives should be routinely consulted about their own desire for CPR in order to avoid resuscitating patients against their wishes. Further research is required to find out how patients would feel about resuscitation if they were terminally ill or chronically confused, and how carers would feel about resuscitating such patients. PMID- 7776349 TI - Professed religious affiliation and the practice of euthanasia. AB - Attitudes towards active voluntary euthanasia (AVE) and physician-assisted suicide (PAS) among 1,238 doctors on the medical register of New South Wales varied significantly with self-identified religious affiliation. More doctors without formal religious affiliation ('non-theists') were sympathetic to AVE, and acknowledged that they had practised AVE, than were doctors who gave any religious affiliation ('theists'). Of those identifying with a religion, those who reported a Protestant affiliation were intermediate in their attitudes and practices between the agnostic/atheist and the Catholic groups. Catholics recorded attitudes most opposed to AVE, but even so, 18 per cent of Catholic medical respondents who had been so requested, recorded that they had taken active steps to bring about the death of patients. PMID- 7776350 TI - Patients' rights--why the Australian courts have rejected 'Bolam'. AB - This point of view compares the issue of informed patient consent primarily as it operates in Australia and the United Kingdom. It affords an overview, also, of the applicable law in the United States and Canada. It particularly focuses on the legal test to be applied to patient consent as established in the Bolam case in the United Kingdom. The case, following its approval by the House of Lords, holds that the negligent standard in patient consent situations is to be determined, in cases of dispute, in accordance with standards as viewed by a proper body of competent medical practitioners. By contrast, the law in the United States is premised on the notion of the fundamental right of patients to determine what should or should not be done with their own bodies. In Australia the Bolam test has been rejected by the High Court of Australia following earlier decisions in the State Supreme Courts. The Australian courts did not accept that the setting of standards by the medical profession was an acceptable way of determining the entitlements of a patient who has suffered harm. The author places this discussion in the context of greater community awareness of medical procedures, the heightened accountability of professionals and the increasing practice of having a substantial patient input into medical decisions. He also suggests that the differing social and professional attitudes to authority and fundamental rights to be found between Australia and the United Kingdom have influenced the outcome of the cases in the higher courts of both countries. He suggests that the Bolam test is an illustration of the tendency of authority in the United Kingdom to believe that 'Nanny know best'. PMID- 7776351 TI - Nutrition, dehydration and the terminally ill. PMID- 7776352 TI - Developing countries: whose views? PMID- 7776353 TI - The ethics of ignorance. PMID- 7776354 TI - The Institute of Medical Ethics: working parties and medical groups. PMID- 7776356 TI - Continuous measurement of blood gases using a combined electrochemical and spectrophotometric sensor. AB - The use of a combined electrochemical and fibreoptic continuous intra-arterial blood gas sensor is described. The purpose of the study was to evaluate the performance of the sensor in 10 patients in the intensive therapy unit following insertion through a femoral arterial cannula. To our knowledge this is the first published study on the valuation of an intravascular blood gas sensor through a femoral arterial cannula. A total of 71 sets of data comparing the sensor with the blood gas analyser were obtained. The bias and precision for pH, PCO2 and PO2 were 0.006 and 0.07 pH units, 0.2 and 1.65 kPa (4.6% and 29%) and 0.8 and 2.7 kPa (5.1% and 14.3%) respectively. There was a degree of imprecision of the PCO2 sensor, the reasons for which are discussed. In summary, the intra-arterial sensor functioned well when inserted into the femoral artery in post cardiopulmonary bypass patients. There were no complications attributable to sensor placement. PMID- 7776355 TI - The investigation of life-threatening child abuse and Munchausen syndrome by proxy. AB - The use of covert video surveillance in the investigation of suspected life threatening child abuse and Munchausen syndrome by proxy raises important ethical questions. That the recently reported provision of this facility in North Staffordshire was not presented to a Local Research Ethics Committee (LREC) for approval as a research exercise raises important questions about the ethical review of research and practice. The case made for avoiding such review is first set out and then examined. The three main premisses which form the basis of the view that LREC approval is not required are identified and tested in turn. The conclusion is that there is an undeniable element of research involved in the procedure and that the welfare of all those subjected to the surveillance would be best protected by the submission of the protocol to an independent committee for ethical assessment. PMID- 7776357 TI - HYOMEX: a miniature universal testing machine for in vivo biomechanical studies. AB - A miniaturized universal testing machine, HYOMEX, designed for biomechanically testing spinal structures of an anaesthetized research animal, such as a pig, is presented. A variety of mechanical applications such as static and dynamic tests, creep and relaxation tests, and fatigue tests with frequencies up to 20 Hz are possible. The system permits force control as well as displacement control. Continuous surveillance is made possible through interfacing the system to a computer. An application is presented where the viscoelastic behaviour in a porcine lumbar spine was measured. PMID- 7776358 TI - Waveform generator for electrical impedance tomography (EIT) using linear interpolation with multiplying D/A converters. AB - This paper describes the implementation of a multiplying digital-to-analogue (D/A) converter as a programmable waveform generator to be used in an electrical impedance tomography (EIT) system. Different digital techniques of generation waveforms are considered and the advantages and disadvantages of the chosen slope plus-pedestal technique are presented. A wire-wrapped prototype system has been designed, and from measured frequency spectra the total harmonic distortion can be calculated to values between 1.1 and 2.9% depending on frequency. PMID- 7776360 TI - Case records of the Department of Medicine University of Mississippi Medical Center. Sarcoidosis. PMID- 7776359 TI - Comparison of oscillometric and intra-arterial blood pressure and pulse measurement. AB - Non-invasive oscillometric blood pressure and pulse measured by an Omron HEM 703CP monitor were compared with arterial values obtained from direct measurements of the radial artery. An excellent correlation and agreement was found between the two methods (systolic r = 0.99; diastolic r = 0.97; pulse r = 0.99), although there was some variability among individual subjects. The range of difference between them was 0 to 10 mmHg for systolic and -6 to +5 mmHg for diastolic pressures. When tested on the bench using the Metron QA-1280 non invasive blood pressure analyser the HEM-703CP monitor rarely exhibited errors exceeding 2-3 mmHg over a measurement range of 50-200 mmHg. PMID- 7776361 TI - An ethical dilemma. PMID- 7776362 TI - Researchers develop ceramic drug delivery system. PMID- 7776363 TI - Nutritional support of the hospitalized patient: a team approach. AB - Nutritional deficits have long been recognized as contributing factors to morbidity and mortality of hospitalized patients. A multi-disciplinary team approach to nutritional support has been shown to be superior to non-team approaches. A formal consultive nutritional support team has been active at St. Dominic Hospital since 1991. The benefits of our nutritional support team at St. Dominic Hospital are described. Acquisition of an Indirect calorimeter has improved measurements of caloric and substrate requirements. Individualized nutritional prescriptions more closely meet assessed patient needs. Utilization of less expensive, more physiologic enteral feeding routes have increased. Also, the number of total parenteral nutrition (TPN) bags admixed and wasted have decreased, despite an increase in the percent of patients with moderate to severe nutritional risk. The nutritional support service at St. Dominic Hospital has improved patient care while reducing cost to both the institutional and patient. PMID- 7776364 TI - Mapping important nucleotides in the peptidyl transferase centre of 23 S rRNA using a random mutagenesis approach. AB - Random mutations were generated in the lower half of the peptidyl transferase loop in domain V of 23 S rRNA from Escherichia coli using a polymerase chain reaction (PCR) approach, a rapid procedure for identifying mutants and a plasmid based expression system. The effects of 21 single-site mutations, at 18 different positions, on cell growth, mutant rRNA incorporation into ribosomes and peptidyl transferase activity of the mutant ribosomes were analysed. The general importance of the whole region for the peptidyl transferase centre was emphasized by the finding that 14 of the mutants were sick, or very sick, when ribosomes containing chromosomal-encoded 23 S rRNA were inhibited by erythromycin, and all except one of these exhibited low levels of peptidyl transferase activity in their mutated ribosomes. Two mutations, psi 2580-->C and U2584-->G that both yielded inactive ribosomes were assigned to the donor substrate binding site and a possible base-pairing interaction between the 3'-terminal sequence of the peptidyl-tRNA and the sequence psi/U-G-G2582, that is conserved in all the non mitochondrial 23 S-like rRNA sequences, is proposed. Three sites that have been implicated in aminoacyl-tRNA binding were mutated: mutant m6A2503G yielded inactive ribosomes, while ribosomes from mutants Um2552A/C and U2555C yielded low and normal activities, respectively. Three mutants, U2528C, G2550A and A2565U, provide evidence for conformational rearrangements occurring in the peptidyl transferase centre which may be affected by the subunit-subunit interaction. Other mutants which yielded ribosomes that were seriously defective in peptidyl transferase activity were U2493A, U2493C, A2497G, A2530G, G2557A and A2589G. PMID- 7776366 TI - Defects in the Drosophila myosin rod permit sarcomere assembly but cause flight muscle degeneration. AB - We have determined the molecular and ultrastructural defects associated with three homozygous-viable myosin heavy chain mutations of Drosophila melanogaster. These mutations cause a dominant flightless phenotype but allow relatively normal assembly of indirect flight muscle myofibrils. As adults age, the contents of the indirect flight muscle myofibers are pulled to one end of the thorax. This apparently results from myofibril "hyper-contraction", and leads to sarcomere rupture and random myofilament orientation. All three mutations cause single amino acid changes in the light meromyosin region of the myosin rod. Two change the same glutamic acid to a lysine residue and the third affects an amino acid five residues away, substituting histidine for arginine. Both affected residues are conserved in muscle myosins, cytoplasmic myosins and paramyosins. The mutations are associated with age-dependent, site-specific degradation of myosin heavy chain and failure to accumulate phosphorylated forms of flightin, an indirect flight muscle-specific protein previously localized to the thick filament. Given the repeating nature of the hydrophobic and charged amino acid residues of the myosin rod and the near-normal assembly of myofibrils in the indirect flight muscle of these mutants, it is remarkable that single amino acid changes in the rod cause such severe defects. It is also interesting that these severe defects are not apparent in other muscles. These phenomena likely arise from the highly organized nature and rigorous performance requirements of indirect flight muscle, and perhaps from the interaction of myosin with flightin, a protein specific to this muscle type. PMID- 7776365 TI - Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box containing protein into a transcriptional activator. AB - Human mitochondrial transcription factor A (h-mtTFA) is essential for initiation of transcription from the two promoters located in the displacement-loop region of human mitochondrial DNA. This 25 kDa protein contains two tandem, HMG box DNA binding domains separated by a 27 amino acid residue linker region and followed by a 25 residue carboxyl-terminal tail; both the linker and tail are rich in basic amino acid residues. Mutational analysis of h-mtTFA revealed that the tail region is important for specific DNA recognition and essential for transcriptional activation. The critical role of the human tail in transcription was confirmed by constructing chimeric proteins that exchanged similar regions between h-mtTFA and its Saccharomyces cerevisiae homolog, sc-mtTFA. Wild-type sc mtTFA is unable to activate transcription from the human mitochondrial light strand promoter (LSP). Addition of the human tail region to sc-mtTFA conferred LSP-specific promoter activation. In all of the different h-mtTFA mutations tested, transcriptional activation was correlated with specific DNA-binding activity, suggesting that these two functions may be inseparable, a situation entirely consistent with previous mutational analyses of human mitochondrial promoters. PMID- 7776367 TI - The role of ATP in the functional cycle of the DnaK chaperone system. AB - Hsp70 chaperons interact with protein substrates in an ATP-dependent manner to prevent aggregation and promote protein folding. For the Escherichia coli homolog DnaK, we have characterized the ATP hydrolysis cycle as well as the effects of the DnaJ and GrpE cofactors on substrate interaction to reach conclusions on the functional cycle. DnaK ATPase was stimulated by substrates (ninefold) and DnaJ (13-fold) through stimulation of the rate limiting step, gamma-phosphate cleavage (approximately tenfold slower than ADP release). Substrates stimulate ATPase after binding with high affinity (KA < 10 microM) to preformed DnaK-ATP complexes. The rapid binding kinetics lead to the conclusion that ATP-bound DnaK is the primary form initiating interaction with substrates for chaperone activity. The resulting DnaK-ATP-substrate complexes, however, are also characterized by rapid dissociation of bound substrate, but can be stabilized by hydrolysis of ATP (stimulated either by the substrate itself or DnaJ through their effects on the rate-limiting step). Stimulation of the gamma-phosphate cleavage reaction by DnaJ is much more efficient (complete conversion of bound ATP to ADP within five seconds) than that by substrates, indicating the special and important role for DnaJ in stabilization of DnaK-substrate interactions. PMID- 7776368 TI - The origins and consequences of asymmetry in the chaperonin reaction cycle. AB - The binding of nucleotides and chaperonin-10 (cpn10) to the Escherichia coli chaperonin-60 (cpn60) and their effect upon the molecular symmetry has been examined both kinetically and at equilibrium. ATP binds tightly and is hydrolysed on only one heptameric ring of the cpn60 tetradecamer at a time, thus inducing asymmetry in the cpn60 oligomer even in the absence of cpn10. In the absence of cpn10 these seven ATP molecules hydrolyse to form a cpn60:ADP7 complex in which ADP is tightly bound (Kd = 2-7 microM); further ADP binding to form a cpn60:ADP14 complex is weak (K1/2 = 2.3 mM). We conclude that symmetrical nucleotide complexes (with 14 ATP or 14 ADPs) are unstable, demonstrating negative co operativity between the rings. When cpn60 is mixed with cpn10 and ATP the resultant cpn60:ATP7:cpn10 complex is formed rapidly (the rate constant for cpn10 association is > 4 x 10(7) M-1 s-1) and before ATP is hydrolysed (k = 0.12 s-1 per active subunit) to produce an extremely stable cpn60:ADP7:cpn10 complex. This allows ATP association on the unoccupied ring and nucleotide asymmetry in the double toroid is preserved. In "trapping" experiments, where the cpn60:ADP7:cpn10 is challenged with ATP, cpn10 was observed to dissociate at a rate identical to that of steady-state ATP hydrolysis in the presence of cpn10 (k = 0.042 s-1 per active subunit). The spontaneous decay of cpn60:ADP7:cpn10 and any of the major steady-state complexes, under conditions where free nucleotides had been removed, occurred at a rate tenfold lower than ATP hydrolysis. Since the binding of the non-hydrolysable analogue AMP-PNP was unable to induce dissociation of the co chaperonin it was concluded that a transient state following ATP hydrolysis is necessary for the rapid dissociation of cpn10, which occurs once in every cycle. Trapping experiments using sub-stoichiometric concentrations of cpn10, relative to cpn60, show an unchanged rate of cpn10 exchange upon ATP hydrolysis, indicating that the formation of a symmetric, "football"-shaped complex in which two molecules of the co-chaperonin are bound to cpn60, is not an obligatory intermediate in the exchange process. PMID- 7776369 TI - Towards structure-based drug design: crystal structure of a multisubstrate adduct complex of glycinamide ribonucleotide transformylase at 1.96 A resolution. AB - An inhibitor complex structure of glycinamide ribonucleotide transformylase (GAR Tfase; EC 2.1.2.2) from Escherichia coli has been determined with a multisubstrate adduct BW1476U89 to an R-value of 19.1% at 1.96 A resolution. The structure was determined by a combination of molecular and single isomorphous replacement using data from two different monoclinic crystal lattices and collecting data from crystals soaked in 20% (w/v) methyl-pentanediol as cryoprotectant for shock-freezing at -150 degrees C. The multisubstrate adduct is bound in an extended crevice at the interface between the two functional domains of the enzyme. This inhibitor is positioned in the binding site by three sets of tight interactions with its phosphate, glutamate and pyrimidone ring moieties, while its interventing linker atoms are more flexible and adopt two distinct sets of conformations. The highly conserved Arg103, His108 and Gln170 residues that are key in ligand binding and catalysis (His108), have compensatory conformational variation that gives some clues as to their role in substrate specificity and in the formyl transfer. The molecular design of 1476U89 as a multisubstrate adduct inhibitor (Ki approximately 100 pM at pH 8.5), is confirmed as it closely mimics the shape, molecular interaction and combined binding constants of the natural 10-formyltetrahydrofolate (10-CHO-H4F; Km approximately 77.4 microM at pH 8.5) and glycinamide-ribonucleotide (GAR; Km approximately 8.1 microM at pH 8.5) substrates. The stereochemistry of this ligand complex suggests that His108 may act as an electrophile stabilizing the oxyanion of the tetrahedral intermediate that is formed as a result of the direct attack on the 10-CHO-H4F by the amino group of GAR. Structural comparison of the folate binding modes among GAR-Tfase, dihydrofolate reductase and thymidylate synthase reveals that folate derivates bound to GAR-Tfase differentially adopt the trans conformation for the dihedral angle between atoms C-6 and C-9 providing a handle for targeting specific folate-dependent enzymes. The structural information derived from two different discrete conformations of the ligand in the binding site also suggests several leads for the de novo design of inhibitors of GAR Tfase that may develop into useful chemotherapeutic agents. PMID- 7776370 TI - Headful packaging revisited: the packaging of more than one DNA molecule into a bacteriophage P1 head. AB - Like a variety of other bacteriophages, such as T4 and P22, bacteriophage P1 packages DNA by a "headful" mechanism in which the capacity of the viral capsid determines the size of the single DNA molecule that is packaged. Because of the long-standing and general acceptance of this packaging mechanism, we were surprised to discover that some of our observations, using the in vitro P1 packaging system, could be explained by the packaging of less than headful-sized (< 110 kb) DNA molecules into a P1 capsid. To account for these observations, we describe results that support a model of in vitro P1 packaging in which multiple less than headful-sized DNA molecules are taken into a P1 head until that head has been filled. The results further suggest that the phage so generated can occasionally inject more than one DNA molecule into a cell upon viral infection. The data that supports these conclusions are: (1) the DNAs of the circular P1 cloning vectors pAd10sacBII (32 kb) and pNS358 (14 kb) are packaged in vitro with an efficiency of about 6 to 12% of that of longer concatemers of these DNAs. (2) The in vitro packaging of two differentially marked, less than 18 kb plasmid DNAs in the same reaction results in the production of a phage that can occasionally inject both DNAs into the same cell upon infection. (3) Virus particles generated by the packaging of either pAd10sacBII plasmid DNA or the two differently marked plasmids have a density in CsCl equilibrium gradients that is the same as P1 plaque-forming phage, suggesting that the former phage contain a headful of DNA. These results cannot be explained by Cre-mediated site-specific recombination between plasmids in the P1 packaging extracts. Finally, we present in vivo experiments that are also consistent with the headful packaging of multiple DNAs into a P1 head. PMID- 7776371 TI - Mutations that stabilize folding intermediates of phage P22 tailspike protein: folding in vivo and in vitro, stability, and structural context. AB - The folding of the trimeric phage P22 tailspike protein is affected by single amino acid substitutions designated temperature-sensitive folding (tsf) mutations. Their phenotypes are alleviated by two repeatedly isolated global suppressor (su) mutations (su V331A and su A334V) and by two additional substitutions (su V331G and su A334I), accessible through site-directed mutagenesis. We investigated the influence of the suppressor mutations on tailspike refolding in vitro, on its maturation at high expression levels in vivo, and on the rates of thermal unfolding of the native protein. All su mutations improved the folding efficiency in vitro and in vivo, but the relative effects of substitutions at position 334 were more pronounced in vivo, whereas the 331 substitutions were more effective in vitro. V331G caused the strongest increase in refolding yields of any single mutation, and was as effective as the V331A/A334V double mutation, where the two single mutations exhibited an additive effect. Both V331A and V331G retarded thermal denaturation, while A334V did not affect, and A334I accelerated unfolding. A334I is the first mutation found to affect the folding of the tailspike and the thermal stability of the native protein in opposite directions. The observed effects can be rationalized on the basis of the recently determined crystal structure of an N-terminally shortened tailspike. As the backbone dihedral angles of Val331 (phi = -119 degrees, psi = 142 degrees) are unusual for non-glycine residues, V331G and V331A may remove steric strain and thereby stabilize folding intermediates and the native protein. The beta-branched side-chains of Val and Ile substituted for Ala334 in the interior of the protein may improve a hydrophobic stack of residues in the large parallel beta-helix. This is likely important in loosely structured early folding intermediates, but not in the very rigid native structure, where the side-chain of Ile can hardly be accommodated. PMID- 7776372 TI - Structural refinement of the non-fluorescent flavoprotein from Photobacterium leiognathi at 1.60 A resolution. AB - The crystallographically-determined structure of the non-fluorescent flavoprotein (NFP) from Photobacterium leiognathi, a homolog of the bacterial luciferase subunits, has been refined to a conventional R-factor [formula: see text] of 0.175 using synchrotron data between 10.0 and 1.60 A resolution. The molecular structure is a homodimer of beta/alpha domains, the monomer having structural similarities to (beta alpha)8 barrel proteins. However, one beta-strand and three alpha-helices of a typical (beta alpha)8 domain are not present in the NFP structure. The refined structure of NFP consists of the 228 amino acid polypeptide, 191 water molecules, a sulfate ion, and two flavin mononucleotides (FMNs) each with a covalently-attached myristate (C14 fatty acid). Both flavin adducts are well-ordered and have exceptional electron density for both the FMN and the myristate moieties. Each flavin mononucleotide-myristate adduct is characterized by a stereospecific linkage (the S enantiomer) between C-6 of the flavin isoalloxazine ring and the C-3' atom of the fatty acyl chain. The stereospecific nature of this flavin-fatty acid linkage suggests that it is the result of an enzyme-catalyzed reaction, most likely the bioluminescence reaction itself. The myristate chains are buried from solvent in hydrophobic pockets in the interior of the protein. Four amino acid side-chains of the NFP polypeptide have been modeled with alternate conformations. Five of the protein's seven alpha helices have classical C-capping boxes. NFP is dimeric and many of the extensive contacts at the dimer interface are mediated by hydrogen-bonded water molecules as well as by hydrophobic interactions. One of the myristate acyl chains sits between NFP monomers and contributes a significant portion of the hydrophobic interactions at the NFP dimer interface. PMID- 7776373 TI - Structural characterization of the molten globule and native states of apomyoglobin by solution X-ray scattering. AB - Compactness and shape are two of the critical properties that describe the degree of protein folding. Solution X-ray scattering is an effective technique for measuring these properties quantitatively. Structural characteristics of various conformational states of horse myoglobin were studied in terms of size and shape by solution X-ray scattering. The radius of gyration for native holomyoglobin was 17.5 A, while that of the apomyoglobin native state was 19.7 A. Corresponding to the increase in the radius of gyration, the largest dimension of the molecule also increased from 47.5 A to 62.5 A. Both states are globular in shape. The scattering profiles in the high angle region suggest that the apomyoglobin native state has a distinct tertiary structure, and that packing of alpha-helices in the apomyoglobin native state would be looser than that of holomyoglobin. These observations indicate that the native state of apomyoglobin is expanded from that of holomyoglobin, and that the conformations of the two are not identical. The radii of gyration for the acid-unfolded state and the denaturant-unfolded state were 30 A and 35 A, respectively. Both unfolded states have chain-like conformations without any tertiary structures. The radius of gyration and the largest dimension of the molten globule stabilized by trichloroacetate were 23.1 A and 72.5 A, respectively. The molten globule is expanded from the native state although it is globular, and is much more compact than the unfolded state. The bimodal distance distribution function and scattering profile at high-angle region suggest that the structure of the apomyoglobin molten globule contains a core comprising a cluster of multiple alpha-helices and flaring tail(s), which would be a common structural property of the compact denatured state appearing during the folding process. The compactness of each conformational state is highly correlated with the extent of formation of the alpha-helix. PMID- 7776374 TI - Functional characterization of the RNA-binding domain and motif of the double stranded RNA-dependent protein kinase DAI (PKR). AB - The double-stranded (ds) RNA-activated protein kinase, DAI (also known as PKR), contains an RNA-binding domain comprising two tandem repeats of a motif, the dsRBM, which is shared with a number of other proteins that interact with structured RNAs. We have expressed the entire domain and the first copy of the motif in Escherichia coli and purified the two proteins, p20 and p10, to apparent homogeneity in order to study their interactions with RNA and with the intact kinase enzyme. Both p20 and p10 bound preferentially to structured RNA molecules. Competition assays showed that in both cases the order of affinity is dsRNA > VA RNA > tRNA, but the isolated motif bound much less tightly than the entire domain. Measurement of the dissociation constants for dsRNA by quantitative gel mobility shift analysis gave apparent Kd values of 4 x 10(-9) M and 3.8 x 10(-7) M for p20 and p10, respectively. The binding of p20 molecules to dsRNA appeared to be cooperative. Multiple complexes were formed between the intact domain and dsRNA, saturating at a density of about one p20 molecule/11.25 base-pairs (or one turn) of duplex, whereas p10 achieved only about half of this packing density. The apparent Kd for the p20-VA RNA interaction was estimated as 3.5 x 10(-7) M and at least three complexes were detected, but no distinct complexes were visualized for the interaction between p10 and VA RNA. Both p20 and p10 inhibited autophosphorylation of intact DAI, probably by binding the dsRNA activator. Once activated, DAI could phosphorylate both p10 and p20, suggesting that intermolecular phosphorylation can occur. PMID- 7776375 TI - The presence of a D-stem but not a T-stem is essential for triggering aminoacylation upon anticodon binding in yeast methionine tRNA. AB - Dissection of the yeast cytoplasmic initiator tRNA(Met) into two helical domains, the T psi C acceptor and anticodon minihelices, failed to show anminoacylation and binding of the acceptor minihelix by the yeast methionyl-tRNA synthetase (MetRS) even in the presence of the anticodon minihelix. In contrast, based on the measure of the inhibition constant Ki, the anticodon minihelix carrying the methionine anticodon CAU is specifically bound to the synthetase and with an affinity comparable to that of the full-length tRNA. The yeast tRNA(Met) acceptor and anticodon minihelices were covalently linked using the central core sequences of either bovine mitochondrial tRNA(Ser) (AGY) lacking a D-stem or initiator tRNA(Met) from Caenorhabditis elegans lacking a T-stem. Based on modeling studies of analogous constructs performed by others, we assume that the folding and distance between the anticodon and acceptor ends of these hybrid tRNAs are identical to that of canonical tRNA. The three-quarter molecule, which includes the T-stem, has aminoacylation activity significantly more than an acceptor minihelix, while the acceptor stem/anticodon-D stem biloop has near wild-type aminoacylation activity. These results suggest that the high selectivity of the anticodon bases in tRNA(Met) depends upon the tRNA L-shape conformation and the presence of a D-arm. Protein contacts with the D-arm phosphate backbone are required for connecting anticodon recognition with the active site. These interactions probably contribute to fine tune the position of the acceptor end in the active site, allowing entry into the transition state of aminoacylation upon anticodon binding. The importance of an L structure for recognition of tRNA(Met) by yeast MetRS was also deduced from mutations of tertiary interactions known to play a general role in tRNA folding. PMID- 7776376 TI - Pseudoknot in domain II of 23 S rRNA is essential for ribosome function. AB - The structure of domain II in all 23 S (and 23 S-like) rRNAs is constrained by a pseudoknot formed between nucleotides 1005 and 1138, and between 1006 and 1137 (Escherichia coli numbering). These nucleotides are exclusively conserved as 1005C.1138G and 1006C.1137G pairs in all Bacteria, Archaea and chloroplasts, whereas 1005G.1138C and 1006U.1137A pairs occur in Eukarya. We have mutagenized nucleotides 1005C-->G, 1006C-->U, 1137G-->A and 1138G-->C, both individually and in combinations, in a 23 S rRNA gene from the bacterium E. coli. The ability of 23 S rRNA to support cell growth is reduced when either of these base-pairs is disrupted, and it is completely abolished upon disruption of both base-pairs. Each mutant 23 S rRNA is assembled into 50 S subunits, but the mutant subunits do not stably interact with 30 S to engage in protein synthesis. Enzymatic and chemical probing of ribosomal particles reveals increased accessibility in the rRNA structure close to the sites of the mutations. The degree to which the mutations increase rRNA accessibility correlates with the severity of their phenotypic effects. Nucleotide 1131G is extremely reactive to dimethyl sulphate modification in wild-type subunits and ribosomes, but is rendered unreactive when either the pseudoknot is broken or when the r-proteins are removed. The structure of the pseudoknot region is possibly influenced by interaction of an r-protein at or close to the pseudoknot. Re-establishing the pseudoknot Watson-Crick interactions with one "eukaryal" (1005G.1138C or 1006U.1137A) pair and one "bacterial" C.G pair largely restores the structure and function of the rRNA. Bacterial ribosomes containing both these eukaryal pairs also participate in protein synthesis, although at much reduced efficiency, and the structure of their pseudoknot region is partially open and accessible. PMID- 7776377 TI - The structure of the R-type straight flagellar filament of Salmonella at 9 A resolution by electron cryomicroscopy. AB - The supercoiled forms of the flagellar filaments are thought to be constructed from a mixture of two distinct subunit conformations arranged in a regular manner. We analyzed the structure of one of the two straight flagellar filaments, each of which is built up with all its subunits in one of the two conformations. The filament we studied was isolated from the strain SJW1655 of Salmonella typhimurium and had a right-handed helical symmetry. With recent advancements in electron cryomicroscopy, such as a liquid helium temperature stage for frozen hydrated specimens and a stable field emission source, and also by averaging high resolution data with a proper correction of the contrast transfer function, the density distribution map of this straight flagellar filament was generated in far more detail than before by including data up to 9 A resolution. The structure shows a densely packed core region from about 15 to 55 A in radius, where a pair of concentric tubular features of high density is present without well-defined subunit boundaries, and an outer part from 55 to 115 A, where the subunits are mostly well separated from each other. The outer tube in the core region, from 35 to 55 A in radius, contains many rod-like features with near-axial orientation and closest lateral distances of around 10 A, which are most likely to represent the alpha-helical bundles that were predicted in our previous report. In the inner tube, from 15 to 30 A in radius, the rod-like features are less clear. Between the inner and outer tubes are the short spoke-like densities, which are radially tilted and are connecting the two tubes. The outer part, from 55 to 115 A, contains an axially elongated column density and a slewed projection with a narrow neck region. When compared with the other straight filament having left handed helical symmetry, this outer part does not show any significant changes in orientation, suggesting that the switch in the subunit conformation and packing involved in the polymorphic transitions is quite subtle and only occurs within the core region. Reassignment of each structural domain to the amino acid sequence is suggested, based on the volume of each domain, which was determined rather precisely by a proper correction of the contrast transfer function for both amplitudes and phases. PMID- 7776379 TI - Preconditioning stimuli and inadvertent preconditioning. AB - There are several factors besides brief episodes of total coronary occlusion which can provide sufficient stress to result in a preconditioning-like effect on the size of a myocardial infarction. Partial coronary artery stenosis, hypoxia, stretch, catecholamines, rapid pacing, and certain pharmacologic therapies may provide preconditioning stimuli. These same factors as well as mechanical complications in which a coronary artery is briefly occluded or stenosed prior to a subsequent coronary occlusion may lead to inadvertent preconditioning and confound the results of experimental cardiology studies. PMID- 7776378 TI - Structure of bacterial flagellar filaments at 11 A resolution: packing of the alpha-helices. AB - Recent advances in the analysis of electron micrographs of frozen, hydrated bacterial filaments have allowed us to average data from more than 150 images and to reconstruct the bacterial flagellar filament of Salmonella typhimurium at a resolution of approximately 11 A. In addition to the outermost features seen in earlier lower resolution maps of the filament, we find a pair of concentric tubes which surround a approximately A diameter channel at the center of the structure. The walls of these tubes are composed of rod-like features which we have interpreted as columns of individual alpha-helices stacked end-to-end. Each column runs approximately parallel to the helix axis. The wall of the innermost tube, at a radius of approximately 20 A, is formed from 11 such columns. The wall of the second tube is formed from 22 columns which occur alternately at radii of approximately 43 and approximately 47 A. The two concentric tubes are held apart by spacers. These are short, rod-like features, which run approximately parallel to the helix axis. We have interpreted these as additional alpha-helices. By symmetry, each flagellin monomer contributes an alpha-helix to the inner tube, two alpha-helices to the outer tube and a fourth alpha-helix to the spacer. We have tentatively assigned one type of alpha-helix in the outer tube to the approximately 30 C-terminal residues of flagellin while the remaining three alpha helices are assigned to the approximately 70 N-terminal residues. This interpretation of the reconstruction is consistent with available biochemical, biophysical and amino acid sequence information. We also present details of improved methodology to extract and evaluate the original data and also to assess the statistical significance of features in the three-dimensional map. PMID- 7776380 TI - Organization and function of sarcolemmal phospholipids in control and ischemic/reperfused cardiomyocytes. AB - The topic of this review is the lipidic part of the sarcolemma, the plasma membrane of the myocardial cell, and its role in (dis)function of the cardiomyocyte. First the isolation of the sarcolemma and its lipid composition are discussed. These phospholipids are not randomly distributed over the two monolayers of the lipid bilayer and negatively charged phospholipids are exclusively present in the cytoplasmic leaflet of the sarcolemma, which also contains the majority of phosphatidylethanolamine. This distribution is most likely caused by an active transport of these lipids and by an interaction of the headgroup of these lipids with the cytoskeleton. Subsequently the physicochemical properties of sarcolemmal phospholipids are discussed, where it is shown that certain phospholipids prefer non-bilayer phases, and the effects of sarcolemmal phospholipids on trans-sarcolemmal ion fluxes and calcium compartmentation are discussed. In the second part the effect of ischemia on sarcolemmal phospholipids is discussed with regard to: transbilayer distribution, hydrolysis, lateral distribution and sarcolemmal bilayer stability. In our view, onset of ischemia initiates a sequence of events leading to a loss of normal sarcolemmal phospholipid distribution with an outward migration of phosphatidylethanolamine. There follows, as ischemia progresses, loss of sarcolemmal bilayer stability due to the expression of the non-bilayer behavior of phosphatidylethanolamine, leading to irreversible disruption of the sarcolemma and cell death. PMID- 7776382 TI - Pancreastatin stimulates secretion from neonatal rat atrial cells. AB - Atrial myocardial cells store atrial natriuretic factor and secrete the peptide in response to extracellular stimulation. Ventricular myocardial cells also exhibit stimulated secretion of atrial natriuretic factor but with little or no intracellular storage. The stimulated secretion of other proteins from these cells is poorly characterized. In the present study the secretion of sulfated macromolecules from Na2(35)SO4 labeled atrial and ventricular myocardial cells was quantitated. Both cell types secreted a chondroitin sulfate proteoglycan, as evidenced by glycanase digestion. Endothelin-1, a known stimulator of ANF secretion, stimulated secretion from atrial cells about 70% but had no effect on ventricular cell secretion. The differential stimulation of atrial and ventricular cell secretion was not due to the absence of a regulated secretory pathway in the latter cell type since phorbol ester stimulated secretion from both cell types. This result indicates that differences exist in the early steps of signal transduction between atrial and ventricular cells. Pancreastatin, a regulatory peptide derived from chromogranin A, stimulated atrial cell secretion 90%. This result suggests that chromogranin A, which has been identified in atrial secretory granules, may play an autoregulatory role in atrial secretion. PMID- 7776384 TI - Myocardial buffering capacity in ischemia preconditioned rat hearts. PMID- 7776383 TI - Ventricular myocytes isolated from rejecting cardiac allografts exhibit a reduced beta-adrenergic contractile response. AB - Previous experiments using multicellular preparations from rejecting transplanted animal hearts have indicated that a decrease in the contractile response to beta adrenergic stimulation accompanies acute rejection. The precise mechanism of this decreased beta-adrenergic response, which may limit the inotropic reserve in human transplant patients during rejection, is currently unknown. In order to determine whether the decreased beta-adrenergic response is an intrinsic property of the cardiac myocytes from rejecting hearts, we examined the effects of beta adrenergic stimulation (isoproterenol, 10(-8) and 10(-6) M) on the cell shortening of single myocytes isolated from native rat hearts (untransplanted Lewis strain), non-rejecting isografts (Lewis to Lewis heterotopic transplant), and rejecting allografts (Lewis to ACI transplant). The myocytes from isografts demonstrated a significantly increased contractile response to isoproterenol compared to native myocytes (presumably due to denervation supersensitivity), whereas the myocytes from allografts demonstrated a greatly decreased response to isoproterenol compared to both native and isograft myocytes. These results demonstrate that the decreased beta-adrenergic contractile response is an intrinsic property of the rejecting cardiac myocyte. PMID- 7776381 TI - Endothelin-1 contributes to ischemia/reperfusion injury in isolated rat heart attenuation of ischemic injury by the endothelin-1 antagonists BQ123 and BQ610. AB - A potential detrimental role of endothelin-1 in myocardial ischemia/reperfusion injury was studied by use of the endothelin-1 antagonists BQ123 and BQ610. Isolated isovolumetric rat hearts were perfused at constant pressure. BQ123 (7 micrograms/min) and BQ610 (1.75 micrograms/min) did not alter mechanical function or coronary flow and shifted dose-response curves for endothelin-1 significantly to the right. In rats subjected to 30 min of no-flow ischemia, the increase of left ventricular resting pressure was significantly delayed by BQ123 and BQ610 compared to control (BQ123: 20 +/- 2* mmHg, BQ610: 19 +/- 2* mmHg, control: 44 +/ 4 mmHg at 15 min of ischemia, respectively, *P < 0.05 v control). With reperfusion after 30 min of ischemia, recovery of left ventricular developed pressure was not significantly affected but tended to be better with endothelin-1 antagonist pretreatment (BQ123: 20 +/- 3 mmHg; BQ610: 19 +/- 3 mmHg, control 12 +/- 3 mmHg). However, in hearts subjected to 15 min of ischemia followed by reperfusion, recovery of left ventricular developed pressure was improved by BQ610 pretreatment (BQ610: 52 +/- 8* mmHg, control: 24 +/- 6 mmHg). We conclude: BQ123 and BQ610 effectively antagonize the coronary constrictive effect of endothelin-1. BQ123 and BQ610 delay the development of contracture during ischemia and may improve functional recovery during reperfusion. Our findings suggest that endogenous endothelin-1 may contribute to ischemia/reperfusion injury. PMID- 7776385 TI - Alterations of excitation-contraction coupling in stunned myocardium and in failing myocardium. AB - Although both myocardial stunning and chronic heart failure are characterized by contractile dysfunction, there are profound differences in their underlying mechanisms. Changes in cardiac contractile force can be effected by modulation of intracellular [Ca2+] or by alteration of the contractile protein response to intracellular Ca2+. New evidence suggests that the principal lesion in the stunned myocardium resides at the level of the contractile proteins, which may be injured by proteases activated early during reperfusion. In contrast, failing myocardium is known to display abnormal intracellular Ca2+ handling, indicative of dysfunction of the sarcoplasmic reticulum. Alterations of gene expression and isoform switching of the myofilaments also occur in failing myocardium, consistent with an observed shift of the kinetics of crossbridge cycling. In conclusion, changes in both intracellular Ca2+ homeostasis and myofilament function occur in failing myocardium, while stunned myocardium primarily reflects an uncoupling between Ca2+ and contractile force. PMID- 7776387 TI - Autoinduction of mRNA and protein expression for transforming growth factor-beta S in cultured cardiac cells. AB - Although transforming growth factor-beta s (TGF-beta s) are expressed widely in both adult and embryonic rat heart, both mRNA and protein expression increase following ischemic injury. Furthermore, exogenous administration of TGF-beta decreases cardiac damage following ischemia-reperfusion in rats. We have found that treatment of primary cultures of neonatal rat cardiomyocytes or cardiac fibroblasts with TGF-beta 1, 2, or 3 results in increased expression of TGF-beta 1, 2, and 3 mRNA. TGF-beta 2 was generally the least effective isoform in inducing TGF-beta expression. In cardiac fibroblasts mRNA expression of all TGF beta s increased 2-3-fold following 1 h of treatment and decreased to control levels by 8 h which was accompanied by a 2.5- and 2.3-fold increase in TGF-beta 1 and 2 protein secretion, respectively. By 48 h of treatment mRNA levels for TGF beta s 2 and 3 were less than 10% of control levels. In cardiomyocytes two-five fold increases in mRNA levels were observed following 1-24 h of TGF-beta 1 treatment, but TGF-beta 1 and 3 mRNA levels returned to control values by 48 h while TGF-beta 2 mRNA expression remained elevated. TGF-beta 1 and 2 protein secreted by the cardiac myocytes was increased 2.9- and 1.7-fold, respectively. Autoinduction of TGF-beta s may play a beneficial role in cardiac wound healing by sustaining transient increases in TGF-beta levels from either endogenous synthesis or exogenous application. PMID- 7776386 TI - Intracellular compartmentation of troponin T: release kinetics after global ischemia and calcium paradox in the isolated perfused rat heart. AB - The marked differences in troponin T serum concentrations observed in patients with reperfused and non-reperfused myocardial infarction may be due to a perfusion dependent wash-out of an unbound fraction of cardiac troponin T. To test the release kinetics of troponin T experimentally, the isolated rat heart (Langendorff preparation) was damaged either by the calcium paradox or by no-flow ischemia. Following membrane damage by the calcium paradox troponin T (TNT) showed the same release kinetics in the coronary effluent as the cytosolic markers creatine kinase (CK) or lactate dehydrogenase (LDH). Peak levels of troponin T (282 +/- 58 micrograms/l), CK (6754 +/- 1642 U/l), and LDH (5817 +/- 1730 U/l) occurred 5 min after onset of reperfusion with calcium containing buffers and returned to 9.9%, 1.3%, and 1% of their respective peak levels within 55 min of reperfusion. During reperfusion after no-flow ischemia different release kinetics were found for cytosolic enzymes and troponin T. After 60 min of ischemia, troponin T levels in the coronary effluent increased over the entire reperfusion period of 55 min, almost doubling the 5 min value (191%). In contrast, cardiac enzymes rapidly declined to 18% (CK) and 23% (LDH) of their respective 5 min values at the end of reperfusion. Light microscopy after reperfusion with carbon black revealed a complete and homogeneous reperfusion of Langendorff hearts after no-flow ischemia. Immunoblot analysis confirmed the release of an undegraded 39 kDa troponin T molecule, both after global ischemia and the calcium paradox. These data indicate that prolonged ischemia induces a continuous liberation of cardiac troponin T, most probably from disintegrating myofibres, whereas membrane damage leads almost exclusively to leakage of a functionally unbound troponin T pool. These findings may explain the biphasic serum concentration changes of cardiac troponin T in patients with reperfused myocardial infarction. PMID- 7776388 TI - Bradykinin receptor and tissue ACE binding in myocardial fibrosis: response to chronic angiotensin II or aldosterone administration in rats. AB - High density angiotensin converting enzyme (ACE) binding is present in the perivascular fibrosis involving intramyocardial coronary arteries and the microscopic scarring of the myocardium that accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought to determine whether bradykinin (BK) receptor binding was associated with ACE binding in each of these experimental models. BK receptor binding was localized and quantified by in vitro quantitative autoradiography, using [125I-Tyr8]BK. In serial sections of the same heart hematoxylin and eosin (H&E) and picrosirius red (PSR) staining were utilized to address cardiac myocyte injury and fibrosis, respectively. Four experimental groups were examined: unoperated, untreated, age/sex matched controls: age/sex matched uninephrectomized control rats receiving a high sodium diet; animals that received AngII (9 micrograms/h sc) for 2, 4 or 6 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 micrograms/h sc) for similar periods of time. We found: (a) myocardial fibrosis, including perivascular fibrosis and microscopic scarring, at week 2 of AngII, but not until week 4 or more of ALDO treatment; (b) low BK receptor binding in normal ventricles that was increased in scars and markedly increased in perivascular fibrosis at week 2 of AngII and each increased further at week 4 and 6 of AngII: (c) low BK receptor binding at week 2 and 4 weeks of ALDO treatment which became markedly increased at fibrous tissue sites at week 6. BK receptor and ACE binding were anatomically coincident and localized to each site of fibrosis in both models. The co-location of BK receptor and ACE binding in these models raises the prospect that fibrous tissue ACE may utilize BK as substrate and BK, in turn, may play a role in fibrous tissue formation. PMID- 7776389 TI - Stable expression and functional characterization of a human cardiac Na+ channel gene in mammalian cells. AB - In order to develop mammalian cell lines expressing a functional human heart Na+ channel gene (hH1), Chinese hamster ovary (CHO-K1) cells and HeLa cells were transfected with the hH1 gene and the bacterial neomycin (neo) resistance gene. In CHO-K1 cells, direct screening for hH1-positive, G418-resistant colonies by functional patch clamp analysis was complicated due to low-level endogenous expression of a brain-type Na+ channel. Therefore, we developed a stepwise strategy for isolation of cell lines expressing functional hH1 Na+ channels: G418 resistant colonies were sequentially analysed for (1) chromosomal integration of hH1 DNA by PCR, (2) specific hH1 mRNA expression by RT-PCR, (3) hH1 protein production by immunoprecipitation with hH1-specific antisera, and (4) hH1 Na+ channel function by patch-clamp analysis. Using this strategy we obtained two CHO K1 cell lines which express functional human heart Na+ channels. However, using the same strategy, we were unsuccessful in obtaining functional, hH1-positive HeLa cell lines, even though hH1 mRNA and protein was produced in these cells. The two CHO-K1 cell lines stably express human cardiac Na+ channels which retain normal electrophysiological characteristics with respect to activation and inactivation. In addition, the Na+ channels expressed in these cells are blocked by tetrodotoxin with an IC50 value of 2.5 microM; consistent with known cardiac Na+ channel pharmacology. The density of channels is high enough to permit recording of pseudomacroscopic currents in excised outside-out patches of membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776390 TI - An analysis of lidocaine block of sodium current in isolated human atrial and ventricular myocytes. AB - Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of the present study was to characterize lidocaine block of Na+ channels in human atrium and ventricle. We used the whole cell voltage clamp technique with low external and internal Na+ concentrations (5 mM) to study the Na+ current (INa) in single human atrial and ventricular cells isolated enzymatically from specimens obtained during surgery. We found that tonic block of peak INa by lidocaine (200 microM, holding potential = -140 mV, 0.1 Hz, at 17 degrees C) was not voltage dependent in either cell type. Reduction of maximal peak Na+ conductance in 41 atrial cells (19.8 +/- 2.7%) and nine ventricular cells (22.6 +/- 1.7%) was virtually identical. The rate of onset of block development was determined during depolarization to either -80 mV or -20 mV. The time course of onset of block was described by a single exponential at -80 mV and by a double exponential at -20 mV. When the rate of block onset during a single conditioning depolarization was compared to that which developed during conditioning by a train of brief pulses (3 ms, 30 Hz), onset was faster during the pulse train. The results were nearly identical for atrial and ventricular INa. The time constants of recovery from block following either single pulse or multiple-pulse conditioning did not differ. These data suggest that lidocaine binds to both the activated and inactivated states of the human cardiac Na+ channel. Using an analytical method based upon the Guarded Receptor Hypothesis, we calculated apparent rate constants describing lidocaine's interaction with the three primary states of the human Na+ channel (resting, activated and inactivated). Rate constants were similar to those reported for other mammalian species. Our results demonstrate that lidocaine block of INa is virtually identical for human atrial and ventricular cells; thus additional mechanisms must be invoked to explain the differential efficacy of lidocaine against ventricular as compared to atrial dysrhythmias. PMID- 7776391 TI - Caretaker compliance with different antibiotic formulations for treatment of childhood pneumonia. AB - To determine the effect of antibiotic formulations on compliance, 400 children, aged 2 months to 5 years, with a presumptive diagnosis of pneumonia, were randomly assigned to receive one of the following formulations of cotrimoxazole: 1. syrup accompanied by a 10-ml measuring cup; 2. syrup accompanied by a 5-ml measuring spoon; 3. tablets; 4. single-dose sachets of antibiotic powder. A research assistant visited the childs' home on the fourth day of therapy, asked the care-giver about compliance, and observed the care-giver prepare a dose of the medication. The remaining amount of medicine was measured, and when possible (n = 151), a urine specimen was tested for the presence of sulphamethoxazole. All of the care-givers reported giving at least one dose on the first day of therapy. By the fourth day, 82 per cent of those receiving syrup were still taking their medication compared to 71 and 55 per cent of those receiving sachets or tablets, respectively (P < 0.01). Of those who received syrup accompanied by a spoon, 38 per cent under-dosed the medicine by at least 30 per cent. Overall, compliance was highly correlated with the care-giver's report of difficulty in administering the medication. Additional research is needed to understand the obstacles encountered by care-givers in administering sachets and tablets. Meanwhile, the use of antibiotic syrup, accompanied by an appropriately sized measuring cup, appears to offer the greatest probability of medication compliance in the treatment of Egyptian children with pneumonia. PMID- 7776392 TI - Neonatal meningitis: a 3-year retrospective study at the Mount Hope Women's Hospital, Trinidad, West Indies. AB - The objective of this 3-year (1988-1990) retrospective study was to report the experience with neonatal meningitis at the Neonatal Intensive Care Unit, Mount Hope Women's Hospital, Trinidad, West Indies. Neonates were included in the study if organisms were cultured from the cerebrospinal fluid (CSF) and/or if there was a pleocytosis (> or = 100/mm3) in the CSF. There were 49 neonates with meningitis out of a total of 17,048 live born (LB) infants during the 3-year period to give an overall incidence of 2.87/1000 LB. This was five times higher than the incidence reported in the literature. There were an additional five who were outborns to give a total of 54 cases. There were 34 males (63 per cent) with a mean birth weight of 2389 g. Antenatal risk factors included preterm delivery (50 per cent), prolonged rupture of the amniotic membranes (37 per cent). Associated maternal conditions included hypertension and antepartum haemorrhage (9 per cent). In contrast to other reported studies, there was early onset of the condition (mean age at presentation was 4 days) and the commonest organism found was Group B streptococcus while the least common were the Gram-negative organisms. Also different in the present study was the high percentage (56 per cent) of meningitis associated with Group B septicaemia, the low mortality rate (13) and the low rate of neurological sequelae (40 per cent). PMID- 7776393 TI - Chronic malnutrition and Trypanosoma cruzi infection in children. AB - The distribution of T. cruzi infection overlaps regions with high prevalence of child malnutrition. We examined the possible association between T. cruzi infection and chronic malnutrition. In a cross-sectional survey conducted among 1900 7-12 year-old schoolchildren in 60 village schools in central Brazil, anthropometric measurements (NCHS) taken from 153 children with at least two positive serological tests for antibodies against T. cruzi (IIF, ELISA, IHA) were compared to two age and sex seronegative matched classmates. Information on children's medical history and socio-economic status (SES) were collected from parents of the participants. Seropositive children had a 2.4-fold risk (95% CI 1.4-4.0) of being stunted (z-score < 2.0 of height-for-age) when compared to uninfected children even after adjusting for confounding variables. Being underweight (z-score < -2.0 of weight-for-age) was also statistically associated with seropositivity to T. cruzi (OR = 2.8, 95% CI 1.4-5.6). No statistical evidence of multiplicative interaction between nutritional status and SES was detected. Further studies on nutrition and metabolism are required to look into a possible physiopathological mechanism for this association. PMID- 7776395 TI - Bejel in Malatya, Turkey. AB - Bejel is a form of endemic syphilis which is transmitted by non-venereal route. According to our knowledge, no cases of bejel have been reported from Turkey for more than 30 years. In this report, three children and their father who suffer from bejel are presented. The history, physical findings, laboratory investigations, treatment and results of the cases are reviewed, and the related literature is discussed. PMID- 7776394 TI - Loss of maternally-acquired measles antibody during infancy in Ilorin, Nigeria. AB - In a study of the prevalence of measles antibody in infants aged 1-9 months detectable antibody was present in 32 per cent. Prevalence was highest in the 4-7 week age group and dropped rapidly with increasing age. In infants 28-35 weeks old, only 7 per cent had detectable antibody. Logistic regression analysis showed that by the end of the seventh month of life only 10 per cent would carry antibody against measles. PMID- 7776396 TI - An investigation into feeding errors of 0-4-month-old infants. AB - This study was carried out on 206 infants seen consecutively at the Pediatric Clinic of our hospital. The feeding errors investigated were: the proportion of infants not exclusively breast-fed, incorrect dilution of formula milk, incorrect dilution of cow's milk, rice flour feed prepared with water, and the use of rice water as a feed. The feeding methods of the infants were compared with their weight for height. Of those infants exclusively breastfed 83 per cent were found to be above 100 per cent as regards weight-for-height. In those receiving supplementary feeds this ratio was significantly lower (P < 0.05). In 20 per cent of cases where the infant had received formula milk and in 14 per cent of cases where the infant had received cow's milk, the milk was found to be overdiluted by more than 40 per cent. PMID- 7776397 TI - Integrated Child Development Services Scheme and nutritional status of Indian children. AB - The Integrated Child Development Services (ICDS) Scheme is one of the major National Human Resource Development Programmes of the Government of India. The programme completed 18 years of its effective operational duration on 2 October 1993. During this period we have conducted various baseline surveys, multicentre longitudinal and periodic studies, and unicentre special study projects to determine the impact of the programme on the nutritional status of children aged 0 to < 6 years and evaluate the coverage of the scheme. The children with normal nutrition in ICDS blocks constituted 50 per cent of the surveyed population in 1976 in comparison to 75 per cent observed in baseline data of 1990 survey. There was a highly significant decrease in severely malnourished children from 21 per cent in 1976 to 7 per cent in 1990. The benefit of the programme was evident in all sections of the society including Scheduled Castes, Scheduled Tribes, Backward and Minority communities. The nutritional services (supplementary nutrition, Vit. A, Iron, and Folic Acid) coverage of the children increased from 25 per cent in 1976 to 53 per cent in 1985 in ICDS blocks in comparison to 42 per cent in non-ICDS blocks, while that for pregnant and lactating women increased from 17 per cent and 14 per cent in 1976 to 25 per cent and 26 per cent 1985, respectively. PMID- 7776398 TI - Applications of molecular biology in parasitic diseases. PMID- 7776399 TI - Cranial sonography in pyogenic meningitis in neonates and infants. AB - Cranial sonography was performed in 34 infants with proven meningitis and with clinical suspicion of its complications, utilizing the patent anterior fontanelle. Twenty-five patients showed various sonographic findings which included ventriculomegaly, echogenic sulci, subdural effusion, ventriculitis, infarction/cerebritis, cerebral oedema, porencephalic cyst, etc. Sonography is safe and cost-effective in diagnosis of complications, and management of pyogenic meningitis in infants. PMID- 7776400 TI - The echocardiographic findings in kwashiorkor. AB - Echocardiography (ECHO), electrocardiography (ECG), and chest radiography (CXR) were performed in 44 children with kwashiorkor, and 44 age- and sex-matched controls. In patients with kwashiorkor, mean values obtained for end diastolic dimension (29.2 +/- 3.8 mm), end systolic dimension (20.9 +/- 2.8 mm), posterior ventricular wall thickness (5.42 +/- 0.57 mm), and shortening fraction (28.2 +/- 4.3%) were significantly smaller than the corresponding values obtained in the controls -38.0 +/- 5.8 mm (P < 0.001), 27.6 +/- 4.5 mm (P < 0.001), 7.07 +/- 0.71 mm (P < 0.001) and 31.4 +/- 4.5% (P < 0.05), respectively. Similarly, mean cardiothoracic ratio (48.6 +/- 3.4%) and QRS amplitude (13.20 +/- 4.85 mm) were significantly (P < 0.001) smaller in subjects than controls, corresponding values being 54 +/- 3.2 per cent and 20.18 +/- 5.12 mm, respectively. In the subjects, there was very good correlation between posterior ventricular wall thickness and cardiothoracic ratio (r = 0.93; P < 0.001) and also between the estimated left ventricular mass and S1 + R6 amplitude (r = 0.89; P < 0.001). PMID- 7776401 TI - Cytogenetic analysis of children suspected of chromosomal abnormalities. AB - Karyotypes were examined in 122 Omani children suspected of having chromosomal abnormalities. A total of 50 (41 per cent) had an abnormal karyotype: 38 (31 per cent) were Down's syndrome whilst a further 12 (10 per cent) had other types of chromosomal abnormalities. These findings suggest that cytogenetic analysis is useful in the investigations of children with congenital anomalies of unknown origin; to confirm clinical diagnosis in children with known cytogenetic syndromes and for genetic counselling. PMID- 7776402 TI - A 4-year study of neonatal meningitis: clinical and microbiological findings. AB - The clinical and microbiological data of 60 neonates, 23 from the Neonatal Unit (Group I) and 37 (Group II) from the General Paediatric Wards with meningitis are presented. The overall prevalence/1000 was significantly lower in Group I (0.36) than in Group II (1.11; P < 0.0001). This low incidence follows the introduction of amikacin for the treatment of the ill neonate in 1986. Streptococcus agalactiae 21 (35 per cent), Klebsiella pneumoniae 17 (28 per cent) and E. coli 10 (17 per cent) were the commonest pathogens accounting for 80 per cent of the cases. Streptococcus agalactiae isolates were uniformly susceptible to penicillin and chloramphenicol. Gram negative isolates showed resistance to ampicillin, chloramphenicol and sulphamethoxazole-trimethoprim. In addition K. pneumoniae isolates showed resistance to gentamycin and amikacin. All isolates were fully susceptible to cefotaxime. Recently, four of six cases of K. pneumoniae in the Neonatal Unit were resistant to amikacin. Low birth weight, additional clinical problems, and ultrasound changes on cranial scanning carried a poor prognosis. Emphasis should be placed on close collaboration between clinicians and microbiologists in the choice of antimicrobial agents and aseptic techniques for the care of neonates. PMID- 7776403 TI - Mid-thigh circumference--role in assessing the nutritional status of children between 6 years and 12 years of age. AB - Children between 6 and 12 years form a group at risk for nutritional lag. It has been seen that their growth and nutritional status can be satisfactorily assessed by measuring the mid-thigh circumference, using a fibreglass measuring tape. PMID- 7776405 TI - Reasons for admission, causes of death and costs of admission to a tertiary referral neonatal unit in India. AB - The aim of this study was to determine the reasons for admission, charges made, and causes of death in a tertiary referral neonatal unit in India. Records of the Christian Medical College Hospital, Vellore, Tamil Nadu, India, were reviewed for the period 1 January-31 December 1992. The principal cause of death was ascertained with reference to predetermined diagnostic criteria. There were 5592 livebirths, 138 stillbirths and 1809 admissions to the nurseries (1603 inborn, 206 outborn). Suspected sepsis accounted for 24 per cent of admissions, 14 per cent required preterm care, 13 per cent phototherapy and 8 per cent were full term low birth weight babies admitted for observation. There were 87 early neonatal deaths, 4 per cent (49) of inborn admissions and 18 per cent (38) of outborn admissions. A further 11 babies were discharged to receive terminal care at home and nine were discharged, critically ill, against medical advice. Causes of death were respiratory problems of prematurity (49 per cent), lethal congenital malformations (22 per cent), complications of asphyxia (20 per cent) and sepsis (5 per cent). The median duration of nursery care was 2 days (range 1 21) and the median charge made Rs 714 (range 122-5036). Although the pattern of admissions and deaths still reflects the substantial problems of suspected sepsis, asphyxia, and congenital malformations, problems of immaturity may be on the increase. We caution against hospital-based statistics that fail to take account of babies who are discharged alive in the knowledge that death is imminent. Considered strategies for the provision or selective provision, of neonatal care in India, are called for. PMID- 7776404 TI - Determinants of nutritional status in south-west Uganda. AB - In a cross-sectional survey carried out of 4320 children 0-59 months old in South west Uganda various socio-economic and environmental factors were related to poor nutritional status. Diarrhoea was strongly associated with all the anthropometric parameters examined, suggesting a bidirectional influence of diarrhoea on malnutrition and of malnutrition on diarrhoea. The other most important variables independently associated with one or more anthropometric parameters were: distance from a health unit, living in a household not able to hire labour, and whose members worked on other people's land, religion, parental education, crowding conditions, sanitation, acreage, ownership of cow, father's occupation, birth order, ethnicity, and prolonged breastfeeding. This data indicates that a range of specific interventions are likely to be necessary for the improvement of nutrition in this community. PMID- 7776406 TI - Randomized double-blind study comparing the efficacy of terazosin versus placebo in women with prostatism-like symptoms. AB - PURPOSE: We attempt to determine whether terazosin is effective therapy for the treatment of prostatism-like symptoms in women. MATERIALS AND METHODS: A total of 29 women 47 to 79 years old with prostatism-like symptoms entered a randomized double-blind study comparing terazosin (14) versus placebo (15). The salient inclusion and exclusion criteria consisted of an American Urological Association (AUA) symptom score of 8 or more, post-void residual volume less than 300 ml. and absence of stress urinary incontinence. RESULTS: The baseline and final visit AUA symptom scores were 12.7 and 10.7 respectively, in the placebo group, and 16.4 and 13.6, respectively, in the terazosin group. The differences between the change in AUA symptom score in the placebo and terazosin groups were not clinically or statistically significant. CONCLUSIONS: Our study demonstrates that terazosin is not effective for the treatment of prostatism-like symptoms in aging women. PMID- 7776407 TI - Symptoms of the transurethral resection syndrome using glycine as the irrigant. AB - We evaluated signs and symptoms of the transurethral resection syndrome recorded during and after 273 transurethral prostatic resections performed at 2 hospitals between 1984 and 1993. Glycine solution was used as the irrigant and ethanol served as a tracer for fluid absorption. The incidence and severity of symptoms that could possibly be related to the syndrome increased progressively as more glycine solution was absorbed. Patients who absorbed 0 to 300 ml. of glycine solution had an average of 1.3 such symptoms. This number increased to 2.3 when 1,001 to 2,000 ml. were absorbed, 3.1 when 2,001 to 3,000 ml. were absorbed and 5.8 for volumes greater than 3,000 ml. Nausea and vomiting occurred significantly more often when 1,001 to 2,000 ml. were absorbed compared to no absorption. Confusion and arterial hypotension were other prominent signs of fluid absorption, whereas hypertension was not. The severity of symptoms was markedly aggravated when more than 3,000 ml. were absorbed. Extravasation resulted in higher risks of bradycardia, hypotension and failed spontaneous diuresis postoperatively than absorption by the intravascular route. PMID- 7776408 TI - Impact of physician awareness on hospital charges for radical retropubic prostatectomy. AB - PURPOSE: We determine if physician awareness of hospital costs for radical retropubic prostatectomy affects physician practice patterns. MATERIALS AND METHODS: We reviewed 256 consecutive radical retropubic prostatectomies performed by 14 urologists during 4 years at a community hospital. After 2 years the physicians were provided information on factors that may decrease charges. RESULTS: Charges decreased significantly following intervention, from +f417,134 within the initial 2 years to +f413,826 within the last 2 years (p < 0.005). Significant decreases were noted for length of stay, need for intensive care, operating time and blood loss. CONCLUSIONS: Traditional methods of physician education can impact practice patterns to decrease hospital charges for radical retropubic prostatectomy. PMID- 7776409 TI - Nerve sparing radical prostatectomy: a different view. AB - Erectile dysfunction was evaluated in 459 men with prostate cancer before and after radical prostatectomy. Potency was defined as the ability to achieve unassisted intercourse with vaginal penetration. Of the patients 51 were potent postoperatively, including 2 of 187 (1.1%) undergoing surgery without nerve sparing, and 27 of 203 (13.3%) undergoing unilateral and 22 of 69 (31.9%) undergoing bilateral nerve sparing prostatectomy. Less than half of the patients who were sexually active postoperatively were satisfied with the erections or achieved intercourse at least once a month. Postoperative potency was statistically related to the number of neurovascular bundles spared, frequency of intercourse preoperatively, absence of seminal vesicle or lymph node involvement with cancer, absence of postoperative incontinence or strictures, patient age and cancer volume. PMID- 7776410 TI - Radical retropubic prostatectomy: the influence of accessory pudendal arteries on the recovery of sexual function. AB - Arterial insufficiency is a major factor responsible for impotence in men following nerve sparing radical prostatectomy. Previously, accessory internal pudendal arteries have been identified traveling over the anterolateral surface of the prostate. Based on this observation, during the last 7 years we have consistently looked for the presence of these arteries and have developed a surgical technique for their preservation. Between 1987 and 1994, 835 potent men underwent radical prostatectomy and accessory pudendal arteries were identified in 33 (4%). Following the development of the surgical technique, it was possible to preserve arteries in 19 of 24 patients (79%). Followup evaluation of 1 year or longer was available for 22 men who did not undergo wide excision of a neurovascular bundle. Recovery of erection sufficient for unassisted intromission and orgasm occurred in 8 of 12 patients (67%) in whom the arteries were preserved and in 5 of 10 (50%) in whom the arteries were sacrificed. We conclude that 1) the presence of accessory internal pudendal arteries is rare (4%); 2) although these arteries were preserved in 79% of the patients, dissection of these arteries from the dorsal vein complex may be associated with excessive bleeding, and 3) because potency rates are similar in men with or without preservation of accessory arteries, routine preservation may not be productive. PMID- 7776411 TI - A worse prognosis for smokers with prostate cancer. AB - To identify phenomena that might explain a higher mortality-to-incidence ratio for prostate cancer among smokers, 359 patients with newly diagnosed tumors at a community hospital were analyzed by tumor stage and grade, host age, obesity, smoking habits and survival. Among the 235 men with nonstage A tumors, stage D disease was independently related to host smoking (odds ratio 2.1, 95% confidence interval 1.3 to 4.3, p = 0.015), as well as to higher tumor grade, younger host age and lack of obesity. Stage D disease was present in 69% of 16 heavy smokers, 41% of 44 other smokers and 31% of nonsmokers. The 5-year tumor-specific mortality rate was greater among smokers than nonsmokers with stage D2 disease (88% versus 63%, p < 0.05) or with nonstage A disease (39% versus 17%, p < 0.001). These observations are compatible with earlier metastasis and more aggressive subsequent tumor advancement in smokers, and indicate that smoking habits may contribute to differences in prostate cancer prognosis between populations. PMID- 7776412 TI - Prostate cancer--neurovascular preservation; smoking cessation may enhance prognosis? PMID- 7776413 TI - Incontinence after radical prostatectomy: detrusor or sphincter causes. AB - PURPOSE: Prospective studies have shown a high prevalence of decreased compliance immediately after radical prostatectomy, which may be a temporary phenomenon in men in whom incontinence persists for more than 1 year. We examined the video urodynamic records of 74 consecutive men referred to our urodynamic laboratory with incontinence as the predominant symptom following radical prostatectomy to evaluate voiding parameters and bladder function. MATERIALS AND METHODS: The urodynamic assessment was made an average of 3.8 years postoperatively. All men presented with persistent post-prostatectomy incontinence, and 64 underwent radical retropubic and 10 radical perineal prostatectomy. RESULTS: A total of 42 men (57%) had sphincter weakness alone, 29 (39%) had detrusor instability and/or decreased compliance combined with sphincter weakness and only 3 (4%) had detrusor instability alone. Of 29 men with a combination of factors 8 had decreased compliance, with 3 also having detrusor instability. Anastomotic strictures occurred in 24% of the patients. A total of 31 patients voided by straining without demonstrable detrusor contraction (42% overall). CONCLUSIONS: Decreased compliance is an infrequent finding after radical prostatectomy. Detrusor abnormalities in general are rarely the sole cause of incontinence, with sphincter weakness being present in the majority of patients. PMID- 7776414 TI - Predisposing factors of systemic fungal infections of the genitourinary tract. AB - We reviewed 50 patients with genitourinary fungal infections between 1982 and 1992. Infections were classified as simple--localized to the bladder and complex- demonstrated evidence of upper tract and/or systemic infection. Predisposing factors of fungal infections, including diabetes mellitus, prolonged Foley catheter drainage and corticosteroid use, were not significantly different. The incidence of obstructive uropathy (88% versus 20%), malnutrition (88% versus 48%), neoplasia (56% versus 16%), renal failure (24% versus 8%) and prolonged antibiotic use (60% versus 32%) were significantly greater in patients with complex infections. The incidence of fungemia in patients with complex infections was 81% with an associated mortality rate of 36%. Of the patients with complex infections 56% required urological intervention. Given the high incidence of obstructive uropathy with complex fungal infections, upper tract imaging is essential. PMID- 7776416 TI - Snail-headed catheter retriever: a simple way to remove catheters from female patients. AB - A snail-headed catheter retriever was designed to remove the Double-J* catheter from female patients. The catheter can be removed within a few minutes using topical anesthesia at the outpatient department without endoscopic instrumentation and lithotomy position. No infection or bleeding developed following the procedure and all patients tolerated it well. The cost-effective retriever can be used as a convenient alternative for Double-J catheter removal from female patients. PMID- 7776415 TI - Clinical effect of captopril on the formation and growth of cystine calculi. AB - We determined the clinical efficacy of captopril for the prevention of new or stone growth in patients with homozygous cystinuria. Nine patients with a history of multiple cystine stones despite standard fluid and alkalization therapy received 50 mg. captopril, 3 times daily in addition to the standard therapy. Before treatment the rate of new stone formation or stone growth ranged from 0.7 to 2.0 events (mean 1.2) per patient-year for 1 to 3 years of observation (mean 1.9). During treatment the rate ranged from 0 to 3.0 events (mean 1.03) per patient-year for 0.5 to 6 years (mean 2.9). Although statistical significance was not evident for the group as a whole (p = 0.35), our findings suggest that captopril may be clinically efficacious in at least some patients with difficult to control cystinuria. Recommendations regarding its indications in this setting are made. PMID- 7776417 TI - Simplified surgical approach to bladder outlet obstruction following pubovaginal sling. AB - We report a new technique of vaginal patch interposition to relieve bladder outlet obstruction after a suburethral sling procedure when the obstruction is caused by over correction of the urethrovesical angle. In this technique the sling is incised longitudinally in the midline and dissected laterally. A vaginal patch is obtained from the vaginal mucosa, then interposed and sutured between the 2 cut edges of the sling. This method is characterized by simplicity and low morbidity, while preserving the integrity of the suburethral sling to maintain continence. PMID- 7776418 TI - The urologist as a discriminating diagnostician and surgeon. PMID- 7776419 TI - Functional bladder neck obstruction: a rare cause of renal failure. AB - We studied 7 men and 6 women (average age 33 years) who presented in renal failure with obstructive voiding symptoms or retention. Of these patients 11 had a dilated upper tract and 2 had shrunken kidneys. Mean serum creatinine at presentation was 7.0 mg./dl. No abnormality was noted on cysto-panendoscopy, retrograde urethrography and voiding cystourethrography. The patients were initially treated with clean intermittent self-catheterization following 7 to 10 days of indwelling catheterization. The majority of patients had low pressure and low flow rate at initial presentation but high end filling pressure (mean 35.3 cm. water), high voiding pressure (mean 118.9 cm. water), high opening pressure (mean 95.3 cm. water) and low peak flow (mean 5.7 ml. per second) on video pressure flow electromyography. The external sphincter was relaxed during voiding but the bladder neck opened intermittently or inadequately. No proper funneling of the bladder neck was seen. Thus, functional bladder neck obstruction was considered to be responsible for obstructive voiding in these patients. Of the patients 3 void to completion with the help of alpha blockers alone, 5 underwent bladder neck incision and are voiding well, and 5 were practicing clean intermittent self-catheterization at last followup. Serum creatinine returned to near normal in 10 patients. End stage renal failure persisted in 2 patients, 1 of whom underwent renal transplantation and is voiding well but the other died without having undergone renal replacement therapy. In the remaining patient serum creatinine was stable at 3.2 mg./dl. Mean serum creatinine at 6 months of followup was 2.33 mg.%. Bladder neck obstruction is a rare cause of renal failure which can be corrected if treated appropriately. PMID- 7776420 TI - Rufloxacin once daily versus ciprofloxacin twice daily in the treatment of patients with acute uncomplicated pyelonephritis. AB - PURPOSE: We compare the bacteriological and clinical efficacy of rufloxacin and ciprofloxacin in patients with acute uncomplicated pyelonephritis. MATERIALS AND METHODS: A total of 110 outpatients was enrolled in a randomized, double-blind multicenter study and treated for 10 days with 200 mg. rufloxacin daily (after a loading dose of 400 mg. on day 1) or 500 mg. ciprofloxacin twice daily. Bacteriological and clinical efficacy was based on the accumulated outcomes assessed at the end of treatment, and at 2 and 4 to 6 weeks. RESULTS: The bacteriological and clinical success rates of rufloxacin and ciprofloxacin were comparable: 55.6% versus 58.8% and 74% versus 71%, respectively (95% confidence interval -28% to +22% and -20% to +25%, respectively). Both study medications were well tolerated. CONCLUSIONS: Rufloxacin once daily is a good alternative in the outpatient treatment of acute uncomplicated pyelonephritis. PMID- 7776421 TI - Dependence of male voiding efficiency on age, bladder contractility and urethral resistance: development of a voiding efficiency nomogram. AB - The influence of age, urethral resistance and bladder contractility on voiding efficiency was evaluated by pressure-flow studies in 138 men of a mean age of 60 years (range 18 to 86). From these studies the urethral resistance parameter was calculated and the maximum bladder contraction strength was determined. Premature fading of the bladder contraction was quantified by a bladder contraction strength decay factor. Voiding efficiency was expressed by the parameter of post void residual urine volume as a percentage of the initial bladder volume. Multiple regression analysis showed that voiding efficiency depended significantly in descending order of importance on urethral resistance, maximum bladder contraction strength and bladder contraction strength decay factor. Patient age was not an independent factor. Maximum bladder contraction strength and bladder contraction strength decay factor were not correlated, suggesting that maximum bladder contraction strength and its decay constitute different properties of bladder contractile function. A voiding efficiency nomogram is proposed, making use of the values for maximum bladder contraction strength and urethral resistance in individual patients. Such a nomogram may have predictive value for the occurrence of acute retention but it must be tested prospectively. PMID- 7776422 TI - Anuria due to intrarenal blood clots in solitary kidney after change of ureteral stent: resolution with minimally invasive evacuation. PMID- 7776423 TI - Ureterocystoplasty: importance of the proximal blood supply. PMID- 7776424 TI - Neuropathic bladder in setting of severe vitamin B12 deficiency: a case report. PMID- 7776425 TI - Commentary on ESWL and blood pressure. PMID- 7776426 TI - False aneurysm of the common iliac artery after pelvic lymphadenectomy: management of an unusual complication. PMID- 7776427 TI - Prostate cancer: unusual metastases 20 years after 125iodine brachytherapy. PMID- 7776429 TI - Re: A new use of ureteroscopy. PMID- 7776428 TI - New sexually transmitted diseases treatment guidelines. PMID- 7776430 TI - Re: Endo-ureteroplasty with a free urothelial graft. PMID- 7776431 TI - Re: Nitrofurantoin-induced pulmonary hemorrhage in a renal transplant recipient receiving immunosuppressive therapy: case report and review of the literature. PMID- 7776432 TI - Re: Eversion of the tunica vaginalis for prophylaxis of testicular torsion recurrence. PMID- 7776434 TI - Intraluminal wire retrieval of a proximally migrated pediatric Double-J ureteral stent. PMID- 7776433 TI - Pyeloplasty improves renal function and somatic growth in children with ureteropelvic junction obstruction. AB - We studied the systemic effects of pyeloplasty in 38 children with unilateral ureteropelvic junction obstruction. Mean patient age at surgery was 2.5 years and 22 patients were age 1 year or younger. Mean followup was 18 months. We recorded serum creatinine levels, glomerular filtration rate calculated by the Schwartz formula body growth, the degree of dilatation and the excretory curve of the diuresis renogram. Pyeloplasty was effective in decreasing the degree of ultrasonographic dilatation and the excretory curve of the renogram in 36 cases. Two patients required reoperation. Individual renal function improved significantly in children younger than 1 year with preoperative differential function less than 45% but not in older children. Serum creatinine level decreased significantly after pyeloplasty in all children. Likewise, glomerular filtration rate improved significantly in all children. Preoperatively, 72% of children younger than 1 year were below the 50th percentile in height. The distribution of heights became normal after surgery. Overall, percentile rank for height increased in a significant number of patients of all ages. We conclude that unilateral hydronephrosis systemically affects body growth and overall renal function, the salutary effect of pyeloplasty goes beyond the affected kidney and pyeloplasty may be of greater benefit when performed in infancy. These parameters must be considered in protocols designed to compare outcomes in children with hydronephrosis treated surgically with those who are simply observed. PMID- 7776435 TI - Intraoperative spermatic venography reconsidered. AB - We review our most recent experience with varicocelectomy and post-ligation venography in 58 adolescents as followup to our previously reported series. A single injection venogram confirmed the completeness of varicocele ligation in 82% of cases while 2 or more injections were required in the remainder. Venography was not performed in 8 cases because of technical difficulties in 5 or surgeon choice in 3. The recurrence rate was 8.6% and was not statistically significant whether or not venography was performed (p = 0.86). Although intraoperative spermatic venography is technically simple and safe, in our series its efficacy in diminishing the recurrence rate after varicocelectomy was unproved. PMID- 7776436 TI - Extracorporeal shock wave treatment raises blood pressure in borderline hypertensive rats. AB - The long-term sequelae on kidney function and blood pressure of renal shock wave treatment were studied in normotensive Wistar rats, contralaterally nephrectomized Wistar rats and borderline hypertensive F1-hybrids bred from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Renal shock wave treatment raised arterial blood pressure in borderline hypertensive, but not in normotensive, rats. A concomitant impairment of ipsilateral renal function or perfusion was not seen despite macroscopic and microscopic evidence of a loss of functioning parenchyma. We conclude that extracorporeal shock wave treatment, by way of its detrimental effects on the kidney, has the potential to provoke arterial hypertension in rats, provided that a genetic predisposition exists. PMID- 7776437 TI - An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas. AB - Cathepsin D is a widely expressed aspartyl lysosomal protease. Clinical studies in several tumor types have shown a strong correlation between cathepsin D expression and tumor progression. In breast carcinoma, its expression is an independent prognostic factor associated with an increased risk of death. However, there have been no studies evaluating cathepsin D in bladder tumors. Therefore, the aim of this study was to determine the pattern of expression of cathepsin D in a large series of bladder carcinomas and assess its role as a prognostic factor against established variables. The tumors from 105 patients (median age 73) (median follow-up 26 months) with transitional cell carcinoma of bladder were examined. Forty-nine patients had superficial tumors (16 pTa; 33 pT1), 56 had invasive tumors (14 pT2; 42 pT3); there were 35 grade 1/2 tumors and 70 grade 3 tumors. These were stained by a standard immunohistochemical technique with an anti-cathepsin D monoclonal antibody. All 4 normal bladder specimens were positive for cathepsin D. Fifty-four tumors (51%) were positive for cathepsin D and 51 (49%) were negative. Chi square analysis showed a significant positive relationship between negative cathepsin D expression and stage (p < 0.0005), grade (p < 0.0001) and tumor morphology (p = 0.001). There was no relationship between cathepsin D expression and tumor ploidy (p > 0.1) or patient age (p = 0.09). Univariate analysis of disease-free and overall survival showed that negative cathepsin D expression (p = 0.01 and p = 0.0003 respectively), stage (p = 0.004 and p < 0.005 respectively) and grade (p = 0.02 and p = 0.0007 respectively) were associated with significantly worse prognosis. However, in a multivariate analysis of age, stage, grade and cathepsin D expression, only stage remained significant for overall survival (p < 0.005). The observed result for cathepsin D in the univariate analysis is probably due to its strong association with grade and stage. Nevertheless, cathepsin D status was able to provide additional prognostic information for overall survival in invasive tumors when stratifying for grade (p = 0.047), which suggests that it might provide additional prognostic data within particular tumor stages. PMID- 7776438 TI - Expression of cell growth regulated genes in the fetal kidney: relevance to in utero obstruction. AB - Previous studies of fetal urinary tract obstruction (bladder outlet obstruction and ureteral obstruction) in lambs have shown that obstructions created relatively early in gestation (4/10 to 6/10 term) can significantly affect growth of the developing kidney. This suggests that urinary tract obstruction in utero can alter normal mechanisms of kidney growth. However, a mechanism for these effects has not yet been proposed. In this study we have used mRNA expression analysis to characterize the temporal sequence of expression of several growth regulated genes during normal ovine kidney development. The purpose of this study was to test the hypothesis that early obstructions, such as those believed to arise in congenital obstructive uropathy in humans, might have a disproportionate effect on hyperplastic growth if the cellular growth fraction (percent of cells in the organ undergoing DNA synthesis) was greater in the second trimester than in the last. Northern blot analysis of the cell cycle-dependent genes histone H3, c-myc and ornithine decarboxylase (ODC) indicated a progressive, gradual decline in cellular proliferation in the kidney from approximately 60 to 135 days (4/10 term to term) gestation, as evidenced by decreases in the respective mRNA levels. The greatest levels of cell proliferation occurred near the midpoint of gestation. This indirect measurement of decline in cellular growth fraction was reflected in direct measurements of change in relative kidney weight. To test whether this decline in mRNA levels occurs widely among genes expressed in the fetal kidney during this period, relative expression levels of more than 300 anonymous mRNA transcripts were evaluated by differential display analysis. This method showed that genes whose expression patterns resembled the growth-regulated genes constituted less than 5% of the expressed mRNAs identified. These data indicate that intrauterine urinary tract obstructions that arise at or near the midpoint of gestation coincide with the highest rates of cell proliferation occurring in the second and third trimesters and, therefore, might adversely affect mechanisms of cell proliferation. PMID- 7776439 TI - Growth-inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines. AB - Growth stimulation of a variety of cell types by the neurotransmitter serotonin has been reported. We have examined the effects of three serotonin-uptake inhibitors, 6-nitroquipazine, zimelidine and fluoxetine (Prozac, Eli Lilly Co., Indianapolis, Indiana) on human prostate carcinoma cell lines. In vitro, all 3 of these compounds inhibited the proliferation of PC-3, DU-145 and LNCaP cells in a dose-dependent manner. Also, all 3 compounds blocked the uptake of a radiolabeled analog of serotonin by the prostate carcinoma cell lines. The order of potency for inhibition of growth as well as for serotonin uptake was fluoxetine > zimelidine > 6-nitroquipazine. The growth of subcutaneous, PC-3 xenografts in athymic nude mice was significantly inhibited by fluoxetine. These results implicate biogenic amines such as serotonin in the growth of prostate carcinoma cells and indicate the potential use of serotonin-uptake inhibitors for the treatment of prostate cancer. PMID- 7776440 TI - Treatment of renal hydatid disease by pedicled omentoplasty. AB - Renal hydatid disease is uncommon and accounts for only 2 to 3% of all hydatid diseases. The treatment of choice is surgical. Medical therapy is not always satisfactory and radical cure depends mostly on removal of all affected tissue. There is controversy concerning the treatment of residual cavity after evacuation of the cyst. For this problem we performed the pedicled omentoplasty in 4 patients with renal hydatid disease. To our knowledge, this method has not been described previously for renal hydatid disease. Cystectomy with pedicled omentoplasty appears to be safe and effective in the management of renal hydatid disease. PMID- 7776441 TI - Three-dimensional arrangement of collagen and elastin fibers in the human urinary bladder: a scanning electron microscopic study. AB - To clarify the arrangements of collagen and elastin fibers of the urinary bladder, we examined 9 human (male, aged 42 to 72) urinary bladders by scanning electron microscopy with chemical digestion methods. The mucosal layer was divided into 3 portions according to the collagen arrangement: the superficial portion interwoven densely by collagen fibrils, the middle portion layered by flat bundles of collagen fibrils and the deep portion made of a loose network of twisted collagen bundles. In the muscular layer, the smooth muscle fascicles were firmly covered with collagen sheets, while each muscle cell in a fascicle was accommodated by a thin sheath of collagen fibrils. The serosal layer consists of wavy collagen bundles piled up in a sheet, which was intercalated by clusters of adipose cells. Elastic fibers were, on the other hand, sparse throughout the bladder wall, except for denser networks around the blood vessels and muscle fascicles and beneath the peritoneal mesothelium. The arrangements of these components were discussed in relation to the mechanical function and compliance of the urinary bladder. PMID- 7776442 TI - Regional differences in the innervation of the human ureterovesical junction by tyrosine hydroxylase-, vasoactive intestinal peptide- and neuropeptide Y-like immunoreactive nerves. AB - We have used double-label immunohistochemistry to examine the presence and pattern of colocalization of vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), tyrosine hydroxylase (TH) and protein gene product (PGP) in nerve fibers supplying the human ureterovesical junction (UVJ). Several populations of nerve fibers within the UVJ region were identified according to their expression of potential transmitter substances. Presumptive noradrenergic axons containing TH- and NPY-like immunoreactivity (LIR) and non-noradrenergic fibers containing VIP- and NPY-LIR accounted for most of the total (PGP-LIR) innervation and supplied all regions of the UVJ. The distal ureter, Waldeyer's sheath and the trigone were supplied by predominantly noradrenergic TH/NPY-LIR nerve fibers, whereas the majority of fibers supplying the detrusor muscle were non-noradrenergic VIP/NPY LIR axons. The similarity in innervation of Waldeyer's sheath, ureter and trigone is consistent with the notion that these structures are all derived from a common mesodermal origin. Regional differences in innervation were also noted within the musculature of the distal ureter: TH/NPY-LIR fibers were localized to the outer part of the ureter, while VIP/NPY-LIR fibers supplied the inner part. This finding suggests that the different layers of the ureter may be independently controlled by different populations of nerves. The findings of this study support the view that noradrenergic nerves are important in maintaining the tone of the UVJ, but indicate that other neurotransmitters or neuromodulators may also be involved in the control of this region. PMID- 7776443 TI - LAK cell mediated apoptosis of human bladder cancer cells involves a pH-dependent endonuclease system in the cancer cell: possible mechanism of BCG therapy. AB - Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder cancer. However, its mechanism has been only partially elucidated. We studied whether LAK cell killing of human bladder cancer cells occurs via apoptosis (programmed cell death) or necrosis. Fluorescent dye labeled T24 cells were observed to undergo morphologic changes associated with apoptosis in the presence of LAK cells when analyzed under a fluorescence microscope. Furthermore, analysis of the DNA isolated from the cytotoxic assay confirmed that the LAK cell induced death of the T24 cells occurred via apoptosis. By pretreating the LAK cells with antifibronectin antibodies, we were able to significantly inhibit the LAK cell killing of the T24 cells. The percentage of cytotoxicity was reduced from 50% to 13% (p = 0.001), and the apoptotic pattern seen on agarose gel electrophoresis was significantly diminished. There was no significant change in the viability of the LAK cells following treatment with the antibodies. Endonuclease isolation from human bladder cancer T24 cells demonstrated that these cells express a pH-dependent and not a Ca++/Mg++ dependent endonuclease. Significant degradation of a target DNA was observed only in pH 4 to pH 5.6 buffers containing endonuclease from T24 cells and not in pH 6 to pH 8 buffers containing endonuclease from T24 cells. The presence or absence of Ca++/Mg++ in the various pH buffers did not alter the endonuclease activity. Finally, we demonstrated that death of T24 cells can be induced by altering the intracellular pH of the cells to 5.6 or lower with the proton ionophore nigericin. We conclude that LAK cells induce T24 cells to undergo apoptosis and that this process involves the fibronectin molecule present on the LAK cell membrane. Furthermore, the cleavage postulate that, in vivo, LAK cells activated by IL-2 produced by BCG activated CD4+ cells may induce bladder cancer cells to undergo apoptosis. This may partially explain the mechanism whereby BCG achieves its therapeutic effect. PMID- 7776444 TI - Distinct glycoforms of a tumor specific glycoprotein, gp200, in human testis and testicular tumors. AB - We recently purified a 200 kD peanut agglutinin-binding glycoprotein from the embryonal carcinoma cell line HT-E (833K) that is expressed selectively in nonseminomatous germ cell tumors. We now further characterize gp200 using Western blot analysis to compare normal and malignant testicular germ cells for reactivity to peanut agglutinin, a plant lectin that recognizes terminal D galactosyl residues, and GCTM-2, a monoclonal antibody that recognizes a 200 kD keratan-sulfate proteoglycan on human embryonal carcinoma. The results indicate that normal germ cells express gp200 as a membrane-bound 230 kD glycoform that expresses terminal galactose residues. This 230 kD glycoprotein is absent on spermatozoa but present on seminomatous germ cell tumors and somatic tissue and does not express terminal galactose on its carbohydrate side chains. In contrast, nonseminomatous germ cell tumors express a heavily sialylated glycoform of gp200 that does express terminal galactose residues. These results describe a glycoprotein that exists in several glycoforms in normal and malignant testicular germ cells. The differential expression of these glycoforms may help in understanding the ontogeny of germ cell tumors. PMID- 7776445 TI - Expression of nm23 in cell lines derived from patients with metastatic renal cell carcinoma. AB - Reduced expression of nm23 has been associated with increased metastases and decreased survival in a variety of malignancies. In the present study, the expression of nm23 was examined by Northern and Western blot analyses in a series of cell lines derived from patients with metastatic renal cell carcinoma. Two of twelve (17%) informative cell lines derived from 9 patients had loss of heterozygosity at Nm23-H1. Twenty-two renal cancer cell lines derived from primary tumors, 5 cell lines derived from metastatic tumors and 4 short-term cultures of normal proximal renal tubular cells all expressed Nm23 mRNA in varying amounts. On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines. Twenty-eight cell lines derived from renal primary tumors and 8 cell lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins. High or low relative expression of nm23 at the mRNA or protein level did not correlate with survival. The absence of any anomalous pattern of expression of the nm23 genes and the lack of correlation of expression with survival suggests that nm23 does not play a central role in the progression of this tumor type. PMID- 7776446 TI - A new protocol for the followup of renal cell carcinoma based on pathological stage. AB - There is no consensus concerning which laboratory and imaging studies should be obtained to assess patients after radical nephrectomy for renal cell carcinoma. We retrospectively reviewed 158 patients who underwent radical nephrectomy with a final pathological diagnosis of renal cell carcinoma. Of the patients 21 had node positive or metastatic disease and 137 had no evidence of metastases at diagnosis. Of the latter group 19 had pathological stage T1N0M0, 82 stage T2N0M0 and 36 stage T3N0M0 (18 stage T3a, 10 stage T3b and 8 stages T3a and b) tumor. Disease recurred in 0%, 14.6% and 52.8% (50%, 44.4% and 75%) of the patients, respectively. The average interval to recurrence was 29.5 months (range 3.5 to 88.8) for patients with stage T2 carcinoma and 22 months (range 3 to 138) for those with stage T3 disease. Based upon our data, followup studies should include a symptom history, serum liver function studies and chest x-rays at defined intervals. Routine use of bone scans and computerized tomography does not appear to be necessary. PMID- 7776450 TI - Autoaugmentation gastrocystoplasty: early clinical results. PMID- 7776447 TI - The ontogeny of bladder function in the fetal calf. AB - Although numerous experimental studies have addressed urinary bladder physiology and pharmacology, little information is available concerning the ontogeny of bladder function. The present in vitro study describes the developmental aspects of bladder compliance, pressure generation and emptying in bovine fetuses from early second trimester to term (280 days). The results can be summarized as follows: 1) bladder compliance increased 3-fold between early second trimester and term; 2) sustained contractile response to bethanechol was present in all bladders; 3) field stimulation produced a submaximal, nonsustained contraction and an active relaxation when the field stimulus was turned off; 4) bladder emptying in response to bethanechol was nearly 100% in mid- and late-gestational bladders but was only 50% at early gestation; 5) bladder emptying in response to field stimulation was 20% to 40% for all gestational age groups; 6) field stimulated relaxation was observed only in the fetal bladder. These studies demonstrate that bladder physiology in utero is different from postnatal bladder function. The presence of a relaxant response during the fetal period may reflect a unique and significant role of the in utero bladder in protecting the upper urinary tracts from sustained increased pressure. PMID- 7776448 TI - Reactivities of mouse monoclonal antibody K2.7 to renal cancers in complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity. AB - Immunohistochemical analysis by indirect immunoperoxidase staining demonstrated that monoclonal antibody (mAb) K2.7, derived from a mouse immunized with a renal cell carcinoma (RCC) cell line OS-RC-2, reacted with 89 of 95 renal cancer tissues (94%). Only 1 gastric and uterine cancer tissue showed positive staining among 87 cancer specimens from 9 different organs. Among normal human tissues, the renal tubule, testis, epithelium of the uterine endometrial gland and Fallopian tube, grey matter of cerebrum and cerebellum, and foreskin showed positive staining. Serological analysis by protein A mixed hemadsorption (PA) assay demonstrated that mAb K2.7 reacted with 25 of 31 RCC cell lines (81%), but with only 2 of 50 other cell lines from different organs. The specific antitumor activities of mAb K2.7 against RCC cell lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) assays. In the CDC assay, all of the 9 RCC cell lines reactive serologically with mAb K2.7 were killed by mAb K2.7 with normal human serum, and the killing activity of mAb K2.7 correlated well with the reactivity of mAb K2.7 in the PA assay. mAb K2.7 showed the same killing activity against each of 3 RCC cell lines with sera from 9 patients with low and high stage renal cancers, as well as with normal human serum. In the ADCC assay, mAb K2.7 with peripheral blood leukocytes (PBLs) from 4 healthy donors showed cytotoxic activity against RCC cell lines. Peripheral blood leukocytes from the same 9 renal cancer patients also showed significant killing activity against the 3 RCC cell lines. These findings suggest the potential utility of mAb K2.7 for specific immunotherapy of renal cancer. PMID- 7776449 TI - Cytoreductive surgery for stage IV renal cell carcinoma. AB - To facilitate the regression of extra renal disease in response to systemic therapy, cytoreductive surgery has been advocated as step 1 in the treatment of stage IV renal cell carcinoma. To determine the effect of surgery on subsequent clinical course, we reviewed the treatment records of 30 patients with known stage IV carcinoma of the kidney who underwent nephrectomy or additional procedures in preparation for systemic therapy. Of 30 patients only 7 (23%) underwent systemic therapy postoperatively. Progression of the disease, surgical morbidity and mortality were the factors preventing 77% of our patients from continuing with treatment. Since regression of extra renal lesions is the goal of systemic therapy, our data suggest that nephrectomy and most other cytoreductive operations in preparation for systemic therapy are not efficient treatment strategies. PMID- 7776451 TI - Renin in Wilms' tumor: prorenin as an indicator. PMID- 7776452 TI - A perspective on renal cell carcinoma. PMID- 7776453 TI - Transurethral resection of the intramural ureter as the first step of nephroureterectomy. AB - Nephroureterectomy is the standard surgical approach for upper urinary tract carcinoma. In 1952 a modified technique was described based on a prior endoscopic disconnection of the intramural ureter as an initial step for subsequent nephroureterectomy via a single lumbar incision. Since October 1989 we performed 31 nephroureterectomies with this technique in 26 men and 5 women (average age 64.5 years). Of the patients 9 had prior bladder carcinoma. The predominant pathological diagnosis of the nephroureterectomy specimens was high grade infiltrating tumor. There were no intraoperative complications except for 1 case of intra-abdominal extravasation detected in the immediate postoperative period and treated conservatively. With an average followup of 20 months, tumor has not recurred at either the resected trigonal area or the retroperitoneum. We believe that our experience assesses the feasibility of this technique to improve and simplify nephroureterectomy, thus, decreasing the morbidity rate and operating time while maintaining the same oncological radicality. PMID- 7776454 TI - Further experience with the modified ileal ureter. AB - A total of 50 patients for whom an ileal ureter was indicated was prospectively randomized between 2 treatment groups according to the surgical technique used. In group 1 the standard ileal ureter procedure was performed, while in group 2 a tailored and valved (modified) ileal ureter was fashioned. Of the patients 19 in group 1 and 23 in group 2 were available for followup of 69 +/- 5.8 months (range 60 to 80). Among the 23 patients in group 2, 5 (22%) experienced reflux due to dessusception of the nipple valve and 4 (17%) had bladder stones. Metabolic acidosis was observed in 9 patients in group 1 (47%) and 4 in group 2 (17%). Urinary outflow obstruction occurred in 5 patients in group 1 and 1 in group 2. Although renal function was comparable among patients in both treatment groups, comparison between patients in group 1 and those without reflux in group 2 showed better renal function in the latter group. We conclude that reflux prevention is of central importance in preservation of renal function in patients with an ileal ureter. A distal nipple valve at the ileovesical anastomosis is associated with significant problems. These observations would urge urologists to search for a more suitable procedure that provides an efficient antireflux principle with minimal adverse sequelae. PMID- 7776455 TI - Experience in 100 patients with an ileal low pressure bladder substitute combined with an afferent tubular isoperistaltic segment. AB - Between April 1985 and April 1993, 100 consecutive men underwent lower urinary tract reconstruction after cystectomy. An ileal low pressure reservoir using the Goodwin cup-patch principle was combined with an afferent ileal tubular segment. The early complication rate was 11%, including 2 postoperative deaths due to septicemia. After a median followup of 27 months (range 3 to 96) 14 patients required surgery for late complications (intestinal obstruction, urethral stricture or tumor recurrence, hernia or ureteral stenosis). A total of 32 patients died of metastatic bladder cancer and 7 died of other causes. The functional capacity of the bladder substitute was increased to the desired 450 to 500 ml. after 3 to 12 months, which was paralleled by improving urinary continence. After 1 year 92% of the patients were continent by day and after 2 years 80% were continent at night. Upper tract surveillance with excretory urography, renal ultrasound and serum creatinine estimation has shown 4 left ureteral strictures but not significant upper tract deterioration or ureteral recurrence. Significant reflux was not observed during video urodynamics unless the reservoir was overfilled. During voiding, by outlet relaxation and straining if necessary, the intra-abdominal pressure increase with straining acted equally on the reservoir and ureters. Therefore, unlike voiding with a normal bladder, no isolated intravesical pressure increase occurred and, thus, there was no reflux from the reservoir. The combination of an ileal low pressure reservoir with an afferent isoperistaltic ileal segment and an open end-to-side ureteroileal anastomosis allows for radical cancer surgery with resection of the ureters where they cross the iliac vessels and minimizes the risk of ureteral stenosis. The unidirectional peristalsis of the ureters and the afferent tubular ileal segment seem to protect the upper urinary tract sufficiently. The surgical technique is straightforward and allows for later conversion to an ileal conduit if necessary. The functional results of the bladder substitute are comparable to other similar reservoir techniques, provided that the patients are carefully selected, well rehabilitated and meticulously followed. PMID- 7776457 TI - The vesical blood-urine barrier: a relevant and dynamic interface between renal function and nervous bladder control. PMID- 7776456 TI - Hematuria home screening: repeat testing results. AB - To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs. PMID- 7776458 TI - Intravesical recombinant tumor necrosis factor in the treatment of superficial bladder cancer: an Eastern Cooperative Oncology Group study. AB - We tested and proved the safety of recombinant human tumor necrosis factor given intravesically weekly for 11 weeks (dwell time 2 hours) for the treatment of superficial bladder cancer in 8 men and 1 woman 46 to 87 years old (mean age 69 years). Cohorts of 3 patients received 200, 400 and 1,000 micrograms. recombinant human tumor necrosis factor. The maximal tolerated dose was not achieved. There were 9 episodes of urological symptoms, 8 of flu-like symptoms, 4 of headache and 3 of chest tightness. Hematological and gastrointestinal toxicities were minor, and no renal toxicity was encountered. Recombinant human tumor necrosis factor was safe to administer at doses up to 1,000 micrograms. We hope that recombinant human tumor necrosis factor in conjunction with other antitumor agents will lead to a new, effective treatment for superficial bladder cancer. PMID- 7776459 TI - Sono-urethrography in the evaluation of anterior urethral strictures. AB - During a 7-year period 123 paired urethrographic and sono-urethrographic studies were performed on 101 patients with 110 urethral strictures. In all but 3 cases the urethra was subsequently evaluated either cystoscopically or at open operation. Sono-urethrography readily identified urethral calculi, diverticula and false passages. It correctly identified the stricture and its site in every case. There was a significant difference between stricture length as measured by urethrography compared to that measured by sono-urethrography (p < 0.003). However, if the strictures were grouped based on anatomical location, there was good correlation and no significant difference in the penile urethra (correlation coefficient = 0.94, p = 0.74) but poor correlation and the significant difference remained in the urethral bulb (correlation coefficient = 0.64, p < 0.007). Similarly, when urethrographic and sono-urethrographic stricture lengths were compared with operative lengths, in the penile urethra the correlation coefficients were close (correlation coefficient = 0.91 versus 0.98) but in the urethral bulb the poor correlation persisted (correlation coefficient = 0.69 versus 0.89). Although sono-urethrography certainly identifies periurethral tissue, it was unreliable in predicting the depth of spongiofibrosis when compared with full depth biopsies in 36 patients with histopathological correlation. Finally, in 16% of the patients sono-urethrography correctly indicated a reconstructive procedure different from that originally suggested by conventional urethrography. Sono-urethrography is a dynamic 3-dimensional study that accurately identifies stricture site, number and caliber. Compared with conventional urethrography, it more accurately measures stricture length and diameter, and identifies periurethral tissue, making it a valuable adjunct in the evaluation of patients with suspected anterior urethral strictures. PMID- 7776460 TI - Incidence of penile pain after injection of a new formulation of prostaglandin E1. AB - PURPOSE: We determined the incidence of pain with injection of a new formulation of prostaglandin E1. MATERIALS AND METHODS: A total of 63 subjects with erectile dysfunction underwent treatment with the new formulation of prostaglandin E1. Evidence of pain associated with injection was obtained by questionnaire and through questioning. RESULTS: A total of 451 injections was given to 63 subjects in the office, with 16 episodes (3.5%) of pain in 10 (15.9%). Then, 680 injections were performed by 38 subjects at home, with 15 episodes (2.2%) of pain in 8 (21%). Pain was not dose related. CONCLUSIONS: The new formulation of prostaglandin E1 is less likely to be associated with pain compared with alcohol based formulations. PMID- 7776461 TI - Penile prosthesis insertion with corporeal reconstruction with synthetic vascular graft material. AB - Difficulty with penile prosthesis insertion may be encountered in patients with severe cavernous scarring or tunica albuginea deficiencies. Eleven patients who underwent penile prosthesis implantation required simultaneous corporeal reconstruction due to prior prosthesis infection and/or erosion in 6, priapism in 2 and Peyronie's disease in 1. One patient underwent prior neophallus construction with a tubularized abdominal wall flap for gender reassignment and 1 had congenitally deficient corporeal bodies. In 4 patients previous additional attempts at prosthesis replacement were unsuccessful. The reconstruction techniques included exposure of the corpora usually through a ventral midline incision and repair with synthetic vascular graft material. Accessory sub-coronal incisions were used when the disease was localized to the distal corpora. Six patients required reconstruction of more than half of the corporeal lengths bilaterally and in 5 smaller portions were repaired. Two patients received a semirigid and 9 an inflatable implant. Mean followup was 46 months (range 5 to 81). One patient required early reexploration for separation of the graft from the tunica and 2 required late surgical revision for distal tip divergence. Healing has been excellent and prosthesis function satisfactory in all patients. Infection, erosion and mechanical failure have not occurred. Penile prosthesis insertion with corporeal reconstruction using synthetic graft material is possible in these cases with acceptable morbidity rates and satisfactory erectile function. PMID- 7776462 TI - Impotence. PMID- 7776463 TI - Optimum abstinence time for cryopreservation of semen in cancer patients. AB - Although an abstinence period of 48 to 72 hours is the most commonly prescribed interval for diagnostic semen analysis, to our knowledge the association between the abstinence period and sperm quality after cryopreservation has not been identified. Patients with a malignant disease who are consulting for semen banking most often require urgent therapy. Consequently, defining the shortest abstinence period that allows for frequent semen collection within a limited interval and the best post-thaw sperm quality is necessary. We investigated the relationship between abstinence period, and the pre-freeze and post-thaw motility variables in semen specimens obtained from cancer patients for sperm banking. Samples collected from 95 patients were divided according to abstinence period: group 1-15 patients at 24 to less than 48 hours, group 2-53 at 48 to less than 72 hours and group 3-27 at more than 72 hours. Pre-freeze and post-thaw motile sperm count and motion variables (motility, velocity, linearity, amplitude of lateral head movement and motility index), and percentage decrease in sperm variables after cryopreservation were analyzed. Semen volume, the pre-freeze and post-thaw motile sperm count, motion parameters and the percentage decrease in semen variables did not differ significantly among the groups. We conclude that semen collection for cryopreservation after 24 to less than 48 hours of abstinence results in post-thaw quality comparable to that after an abstinence of 48 to less than 72 hours or longer. Thus, an abstinence period of 24 to less than 48 hours can be recommended for sperm banking in cancer patients. PMID- 7776465 TI - Management of the epididymal tubule during an end-to-side vasoepididymostomy. AB - Microsurgical repairs of epididymal obstruction have improved because of specific tubule anastomoses. However, these techniques require considerable microsurgical skills and any modifications to organize and simplify these procedures seem desirable. Four modifications are described for the management of the epididymal tubule during end-to-side vasoepididymostomy, including closed tubule fixation, micro-tubulotomy, micro-suction and placement of double-armed sutures through the epididymal tubule before attachment of the vas. These procedures have been performed on 51 patients. "Mixed procedures," or a modified vasoepididymostomy on 1 side and a vasovasostomy on the other, were done in 32 cases and "pure procedures," which included bilateral modified end-to-side vasoepididymostomy (16) and unilateral procedures (3), were done in 19. The semen and pregnancy data for the 19 cases of pure procedures were patency rate 58% in 11 and pregnancy rate 42% in 8. These modifications appeared to be helpful to organize and simplify several aspects of the procedure, and the results were improved compared to other techniques. PMID- 7776464 TI - Outcome prediction in patients with Fournier's gangrene. AB - We treated 30 patients with Fournier's gangrene during a 15-year period. Data were collected on demographics, medical history, admission signs and symptoms, physical examination, admission laboratory studies and bacteriology. The timing and degree of surgical debridement as well as antibiotic therapy were also reviewed. The extent of disease was calculated from body surface area nomograms. Data were stratified according to the outcomes of death (13 patients) or survival (17). Patients who survived were significantly younger (53 years old, range 23 to 90) than those who died (71 years old, range 53 to 83, p = 0.004). Admission laboratory parameters that were statistically related to outcome included hematocrit, blood urea nitrogen, calcium, albumin, alkaline phosphatase and cholesterol levels. White blood count, platelets, potassium, bicarbonate, blood urea nitrogen, total protein, albumin and lactic dehydrogenase levels 1 week following hospitalization were also associated with outcome. The greater mean extent of body surface area involved among patients who died was not statistically different from that of those who lived (7.16 and 4.32%, respectively, p = 0.1). The number of surgical debridements did not seem to influence outcome. To assess better the physiological profile of the patients in both outcome categories, the acute physiology and chronic health evaluation II severity score was modified to create a Fournier's gangrene severity index. The mean Fournier's gangrene severity index for survivors was 6.9 +/- 0.9 compared to 13.5 +/- 1.5 for nonsurvivors. Regression analysis demonstrated a strong correlation between Fournier's gangrene severity index and death rate (correlation coefficient = 0.934, p = 0.005). Using a Fournier's gangrene severity index threshold value of 9, there was a 75% probability of death with a score greater than 9, while a score of 9 or less was associated with a 78% probability of survival (p = 0.008). In conclusion, Fournier's gangrene is an infectious disease affecting an ever aging population of patients. Deviation from homeostasis is the most important parameter predictive of outcome and not the extent of disease or performance of surgical debridement. The Fournier's gangrene severity index is an objective and simple method to quantify the extent of metabolic aberration that may be used to predict outcome. We recommend the use of the Fournier's gangrene severity index when evaluating therapeutic options and reporting results. PMID- 7776466 TI - Femorotibial bypass for claudication: do results justify an aggressive approach? AB - PURPOSE: The role of infrainguinal arterial reconstructive surgery for claudication is controversial. We reviewed the results of femorotibial bypass procedures performed in a select group of patients with disabling claudication in an attempt to define a role for this aggressive approach. METHODS: Data were retrieved from the vascular registry, and hospital records were obtained for all patients undergoing femorotibial reconstruction for disabling claudication during the past 16 years at Brigham and Women's Hospital. Follow-up interviews were obtained to assess overall health, walking impairment, functional status, and patient satisfaction. RESULTS: During a 16-year period a total of 57 tibial reconstructions were performed in 53 patients for claudication (5% of all infrainguinal vein reconstructions). Autogenous vein conduit was used in all cases, most of which (70%) involved the greater saphenous vein in situ. Distal anastamoses were to the tibioperoneal trunk (12%), anterior tibial (18%), posterior tibial (47%), and peroneal (23%) arteries. Major complications occurred in 9%, and no perioperative deaths occurred. Overall 5-year survival was 54% +/- 15%, and no major amputations were performed. Cumulative primary and secondary graft patency at 5 years were 81% +/- 6% and 86% +/- 5%, respectively. Patency rates were significantly better than those achieved in a concurrent series of tibial bypasses for limb salvage and were equivalent to those achieved with femoropopliteal bypass for claudication. Interviewed patients reported improved walking distance, reduced claudication, and a high degree of overall satisfaction with their operation. CONCLUSION: Results obtained with femorotibial bypass performed for claudication were superior to those obtained for limb salvage and were equivalent to those obtained with femoropopliteal bypass for claudication. The results obtained in this highly selected cohort suggest that patients at low risk with significant functional impairment from claudication, available autogenous vein, and suitable tibial outflow to the ischemic muscular bed can be offered revascularization with the expectation of durable long-term results. PMID- 7776468 TI - Magnetic resonance angiography in the preoperative evaluation of abdominal aortic aneurysms. AB - PURPOSE: Contrast arteriography (CA) is a useful but invasive technique for the preoperative evaluation of patients with abdominal aortic aneurysms (AAA). To evaluate the use of magnetic resonance arteriography (MRA) as a preoperative study we prospectively studied 38 patients undergoing AAA repair. METHODS: All patients underwent biplane CA and MRA with use of a gadolinium-enhanced technique. Radiographic studies were then independently evaluated by blinded radiologists for anatomic findings with CA used as the standard. Studies were then independently evaluated by blinded vascular surgeons, and a surgical plan was made. RESULTS: With CA and intraoperative findings as the standards, MRA proved highly accurate in the determination of multiple key anatomic elements. The proximal extent of aneurysmal disease was correctly predicted in 87% (33/38) patients. Significant iliofemoral occlusive disease was identified with a sensitivity of 83% (5/6). Iliac or femoral aneurysms were detected with a sensitivity of 79% (22/28) and specificity of 86% (41/48). Significant renal artery stenosis was detected with a sensitivity of 71% (12/17) and a specificity of 99% (72/73). Accessory renal arteries were correctly identified in 71% (12/17). Surgeon evaluators correctly predicted the proximal cross-clamp site in 87% (33/38) of patients with use of MRA as compared with the actual operative conduct. Proximal anastomotic sites were correctly predicted in 95% (36/38) with MRA and 97% (37/38) with CA. Renal revascularization was predicted by MRA with a sensitivity of 91% (10/11) and specificity of 100% (65/65). The use of bifurcated aortic prostheses was correctly predicted by MRA in 75% (12/16), which was similar to that predicted by CA (81%, 13/16). CONCLUSIONS: MRA can provide preoperative anatomic information that is equivalent to CA for surgical planning. Because of favorable cost and patient safety considerations MRA will assume increasing importance in the preoperative evaluation of AAA. PMID- 7776467 TI - Photodynamic therapy of vein grafts: suppression of intimal hyperplasia of the vein graft but not the anastomosis. AB - PURPOSE: There is no clinically useful therapy for the suppression of vein bypass graft intimal hyperplasia (IH). Photodynamic therapy (PDT), a technique that uses light to activate otherwise biologically inert photosensitizers to produce cytotoxic effects, has been demonstrated to successfully inhibit experimental IH in balloon-injured arteries. The purpose of this study was to investigate the efficacy of PDT as a method to reduce vein graft IH. METHODS: Reversed external jugular vein bypass grafts of the common carotid artery were performed in 28 male Sprague-Dawley rats. The animals received either chloroaluminum sulfonated phthalocyanine (2.5 mg/kg intravenously) 24 hours before the ex vivo irradiation of the vein grafts (VG) with 100 joule/cm2 at 675 nm (PDT VG) or saline solution as control (CON VG). Preharvest bromodeoxyuridine was administered to label proliferating cells. All vein grafts were perfusion fixed within 96 hours for a pilot study or at 2 and 4 weeks for the main study. Histology, immunohistochemistry, and morphometric analysis were performed. RESULTS: There was no acute thrombus formation in the hypocellular PDT VG with occasional platelets but no leukocytes adherent to the luminal surface. Intimal areas of the PDT VG were 18% at 2 weeks and 53% at 4 weeks of the CON VGs (p < 0.05). Medial areas and percent of stenoses were also significantly less in PDT than in CON VG. However, intimal hyperplasia noted in the longitudinal sections within 2 mm of the anastomoses did not demonstrate a difference between PDT and CON VG. Intimal hyperplasia of both PDT and CON VG consisted of smooth muscle cells, verified by immunohistochemistry. Bromodeoxyuridine-labeled cells were more abundant in 2 week than in 4-week specimens, were found most frequently in the intimal areas of the CON VG body, and were equivalent in the anastomoses of PDT VG and CON VG. CONCLUSIONS: These data suggest that PDT of vein grafts suppresses the development of IH in the body of the vein graft but does not affect IH adjacent to the anastomoses. The artery may be the source of proliferating smooth muscle cells that contribute to the anastomotic vein graft IH. PMID- 7776469 TI - Effect of intravenous glucagon on intestinal viability after segmental mesenteric ischemia. AB - PURPOSE: We have previously shown that intravenous glucagon significantly improves rat survival if given after release of superior mesenteric artery occlusion. The purpose of this study was to isolate the effects of glucagon on the intestine by creating a rat model of segmental mesenteric ischemia that avoids the systemic shock associated with total superior mesenteric artery occlusion and reperfusion. METHODS: In 18 anesthetized Sprague-Dawley rats, an 8 cm segment of midileum was made totally ischemic for 110 minutes by occluding its vascular arcades and the bowel ends with microvascular clamps. Control animals (n = 8) received normal saline solution (10 ml/kg/hr intravenously) during ischemia and for 2 hours after declamping. Ten animals also received glucagon (1 microgram/kg/min intravenously) during 2 hours after declamping. After a 24-hour recovery, the ischemic bowel segment, plus nonischemic proximal ileum, was examined histologically by computerized planimetry to measure wall thickness (muscularis, mucosa, and transmural), percent epithelial coverage, and villar surface ratio (villar surface length/bowel circumference). All observations were blinded. Comparisons were made by Student's t test. RESULTS: Compared with nonischemic ileum, the ischemic segment in control animals showed severe mucosal injury with a reduction in mucosal thickness to 25%, epithelial coverage to 23%, and villar surface ratio to 33% of that seen in nonischemic ileum (p < 0.01). Substantial preservation of ileal mucosal viability was seen in glucagon-treated animals. Mucosal thickness and epithelial coverage were twice as well preserved in glucagon-treated rats compared with control rats (p < 0.05), and villar surface ratio was also increased significantly (p < 0.05). The muscularis was not significantly injured in this model. CONCLUSIONS: By use of quantitative histologic measurements, we found that intravenous glucagon significantly improved ileal mucosal viability when given early during reperfusion after segmental ischemia. The mechanism of this effect and its potential clinical application merit further study. PMID- 7776470 TI - Should percutaneous transluminal renal artery angioplasty be applied to ostial renal artery atherosclerosis? AB - PURPOSE: The purpose of this study was to review the results of percutaneous transluminal renal artery angioplasty (PTRA) in patients with atherosclerosis to assess safety, anatomic and functional outcome, and differences in outcome between ostial and nonostial lesions. METHODS: We used retrospective review of 52 consecutive patients who had undergone attempted PTRA for renal artery atherosclerosis during the calendar years 1987 to 1992. RESULTS: Fifty-two patients had 60 renal arteries on whom PTRA was attempted. The mean age was 68 years. Atherosclerosis was generalized in 81% of the patients. The indication for angioplasty was salvage of functioning renal parenchyma in 81% of patients. Eight patients were undergoing dialysis at the time of attempted PTRA. Five arteries (8%) could not be dilated. There were one cardiac death and two arterial complications requiring surgery within 30 days. Thirty-five percent of patients with available angiograms had an anatomic improvement above a threshold of one stenotic group (30% to 40% diameter improvement), with residual stenosis of less than 50%. Half of patients treated for hypertension had improvement in their hypertension. Overall, there was no change in creatinine levels before and after the procedure. Four of eight patients undergoing dialysis at the time of PTRA were able to discontinue dialysis during follow-up. Four patients (11%) required surgical bypass and five patients (14%) required chronic dialysis during follow up. CONCLUSIONS: Modest success at low risk can be expected from PTRA in a group of patients with severe atherosclerosis. No significant difference in results between ostial and nonostial lesions was noted. PMID- 7776471 TI - Simultaneous aortic and renal artery reconstruction: evolution of an eighteen year experience. AB - PURPOSE: We reviewed an 18-year experience with combined abdominal aortic and renal artery reconstruction (AOR) with a particular focus on patients' clinical risk profile and surgical results in contemporary practice as compared with earlier experience. METHODS: One hundred seventy patients underwent AOR during the interval January 1, 1976 to June 30, 1994. To examine parameters representative of current practice, the cohort was divided into group I patients (n = 110) treated before 1990 and group II (n = 60) treated between 1990 and 1994. Median follow-up duration for the entire cohort was 8.4 +/- 0.6 years. Renal artery reconstruction patency and patient survival rates were calculated by life-table methods. Logistic and Cox regression analysis were used to determine predictors of perioperative and long-term morbidity/mortality rates. RESULTS: Although demographic features changed little over the review period, the detection (56% vs 73%, p = 0.03) and treatment with percutaneous transluminal coronary angioplasty/coronary artery bypass grafting (11% vs 40%, p = 0.0001) of associated coronary artery disease were more frequent in group I patients. The operative mortality rate for the entire cohort was 6.5% (group I = 9% vs group II = 2%, p = 0.06). Changing trends of surgical techniques over the review period included (group I vs II, respectively) increased use of bilateral simultaneous renal artery repair (12% vs 25%, p < 0.005) and transaortic endarterectomy as the renal artery reconstruction technique (3% vs 25%, p < 0.0001). Favorable response in blood pressure control was noted in 68% of group II patients. The cumulative 5 year survival rate for all patients was 75% with an initial serum creatinine of 2.0 mg/dl or greater being the only negative predictor of late survival after regression analysis. CONCLUSION: The current operative mortality rate for AOR is in the range anticipated for aortic surgery alone, and this appears to be related to improved detection and treatment of associated coronary artery disease and intervention before major deterioration in renal function. These findings coupled with currently available natural history data relative to renovascular disease justify an aggressive approach with AOR when significant renal artery stenosis is detected during evaluation of aortic disease. PMID- 7776472 TI - Safety and efficacy of transaortic renal endarterectomy as an adjunct to aortic surgery. AB - PURPOSE: A study was undertaken to assess the safety and efficacy of transaortic endarterectomy for orificial atherosclerotic renovascular disease (ASRD), particularly in conjunction with surgery for concomitant aortic disease. METHODS: Forty-three consecutive patients with ASRD treated with transaortic orificial eversion endarterectomy were studied retrospectively to identify surgical indications, technical features, operative morbidity and mortality rates, and efficacy. RESULTS: A total of 76 renal arteries underwent transaortic endarterectomy for hypertension (88% of patients) or serum creatinine of 1.5 mg/dl or greater (65% of patients), including two patients undergoing dialysis. Concomitant aortic surgery was performed in 39 patients for aneurysmal (n = 30) or occlusive (n = 9) disease. Two (2.6%) of 76 renal endarterectomies required intraoperative conversion to bypass because of poor flow, and three arteries (3.9%) were reimplanted or bypassed because of fragility of the renal orifice after endarterectomy. Thirty-day operative death occurred in two patients (4.7%), and major morbidity occurred in six (14.0%). Hypertension was cured or improved in 83% of patients with hypertension. Among patients with preoperative renal insufficiency, function was improved in 19%, with dialysis discontinued in one of two patients receiving dialysis, and function was worse in 23%, with one patient dependent on dialysis. CONCLUSION: Transaortic renal endarterectomy is an acceptably safe and effective adjunctive technique in selected patients with combined aortic disease and ASRD. PMID- 7776473 TI - Comparative early and late cardiac morbidity among patients requiring different vascular surgery procedures. AB - PURPOSE: The evaluation of coronary artery disease (CAD) in patients undergoing vascular surgery can provide information with respect to perioperative and long term risk for CAD-related events. However, the extent to which the required surgical procedure itself imparts additional risk beyond that dictated by the presence of CAD determinants remains in question. The purpose of this study was to quantify the relative contributions of specific vascular procedures and CAD markers on perioperative and long-term cardiac risk. METHODS: The study cohort comprised 547 patients undergoing vascular surgery from two medical centers who underwent clinical evaluation, dipyridamole thallium testing, and either aortic (n = 321), infrainguinal (n = 177), or carotid (n = 49) vascular surgery between 1984 and 1991. Perioperative and late cardiac risk of fatal or nonfatal myocardial infarction (MI) was compared for the three procedures before and after adjustment for the influence of comorbid factors. These adjusted estimates may be regarded as the component of risk because of type of surgery. RESULTS: Perioperative MI occurred in 6% of patients undergoing aortic and carotid artery surgery, and in 13% of patients undergoing infrainguinal procedures (p = 0.019). Significant (p < 0.05) predictors of MI were history of angina, fixed and reversible dipyridamole thallium defects, and ischemic ST depression during testing. Although patients undergoing infrainguinal procedures exhibited more than twice the risk for perioperative MI compared with patients undergoing aortic surgery (relative risk: 2.4[1.2 to 4.5, p = 0.008]), this value was reduced to insignificant levels (1.6[0.8 to 3.2, p = 0.189]) after adjustment for comorbid factors. There was little change in comparative risk between carotid artery and aortic procedures before (1.0[0.3 to 3.6, p = 0.95]) or after (0.6[0.2 to 2.3, p = 0.4]) covariate adjustment. The 4-year cumulative event-free survival rate was 90% +/- 2% for aortic, 74% +/- 5% for infrainguinal, and 78% +/- 7% for carotid artery procedures (p = 0.0001). Predictors of late MI included history of angina, congestive heart failure, diabetes, fixed dipyridamole thallium defects, and perioperative MI. Patients undergoing infrainguinal procedures exhibited a threefold greater risk for late events compared with patients undergoing aortic procedures (relative risk: 3.0[1.8 to 5.1, p = 0.005]), but this value was reduced to 1.3(0.8 to 2.3, p = 0.32) after adjustment. Long-term risk among patients undergoing carotid artery surgery was less dramatically altered by risk factor adjustment. CONCLUSION: In current practice, among patients referred for dipyridamole testing before operation, observed differences in cardiac risk of vascular surgery procedures may be primarily attributable to readily identifiable CAD risk factors rather than to the specific type of vascular surgery. Thus the cardiac and diabetic status of patients should be given careful consideration whenever possible, regardless of surgical procedure to be performed. PMID- 7776474 TI - Variability in measurement of abdominal aortic aneurysms. Abdominal Aortic Aneurysm Detection and Management Veterans Administration Cooperative Study Group. AB - PURPOSE: The purpose of this study was to report interobserver and intraobserver variability of computed tomography (CT) measurements of abdominal aortic aneurysm (AAA) diameter and agreement between CT and ultrasonography observed in the course of a large, multicenter, randomized trial on the management of small AAAs. METHODS: CT measurements of AAA diameter from participating centers were compared with measurements made from the same scan by a central laboratory. Blinded central remeasurement of a randomly selected subset of these CT scans was used to assess intraobserver variability. Agreement between AAA measurements by CT and ultrasonography done within 30 days of each other was also assessed. RESULTS: For interobserver pairs of local and central CT measurements of AAA diameter (n = 806), the difference was 0.2 cm or less in 65% of pairs, but 17% differed by at least 0.5 cm. For intraobserver pairs of central CT remeasurements (n = 70), 90% differed by 0.2 cm or less, 70% were within 0.1 cm, and only one differed by 0.5 cm. Of 258 ultrasound-measured and central CT pairs, the difference was 0.2 cm or less in 44% and at least 0.5 cm in 33%. Ultrasound measurements were smaller than central CT measurements by an average of 0.27 cm (p < 0.0001). Local CT and ultrasound measurements showed a marked preference for recording by half centimeter. CONCLUSIONS: A high degree of precision is possible in CT measurement of AAA diameter, but this precision may not be obtained in practice because of differences in measurement techniques. Differences between imaging modalities increase variability further. Variations in AAA measurement of 0.5 cm or more are not uncommon, and this should be taken into account in management decisions. Efforts to reduce variation in measurement are warranted and might include (1) seeking agreement between surgeons and radiologists on a precise definition of AAA diameter, (2) limiting the number of radiologists who measure AAAs, and (3) use of calipers and magnifying glass for CT measurements. PMID- 7776475 TI - Retroviral vector-mediated transfer and expression of human tissue plasminogen activator gene in human endothelial and vascular smooth muscle cells. AB - PURPOSE: Enhancement of the fibrinolytic activity of vascular cells by tissue plasminogen activator (tPA) gene transfer has considerable clinical potential. However, it is unknown whether greater constitutive expression of the tPA gene might increase plasminogen activator inhibitor-1 (PAI-1) secretion, which could negate expected increases in fibrinolytic activity that accompany greater tPA protein production. The objective of this investigation was to determine whether transduction of human endothelial cells (EC) and vascular smooth muscle cells (SMC) with a retroviral vector containing the human tPA gene would increase tPA production and what effect this would have on endogenous PAI-1 secretion and subsequent fibrinolytic activity. METHODS: Cultivated human EC and SMC either were transduced with a murine leukemia retroviral vector (MFG) containing the human tPA gene and, in the case of controls, the lacZ gene, or they were exposed to media alone. On days 14 and 28 after transduction, supernatent tPA antigen and PAI-1 antigen levels were measured by ELISA, and supernatent tPA activity was quantitated with a spectrolyse tPA/PAI assay. RESULTS: Southern and Northern blot analyses documented integration and transcription of the tPA gene in both EC and SMC. Greater tPA antigen production occurred in MFG-tPA-transduced EC and SMC compared with nontransduced or MFG-lac Z-transduced cells (p < 0.05). The tPA activity increased in transduced human saphenous vein EC (up to 5.1-fold) and human iliac artery EC (up to 4.7-fold), but no increased tPA activity occurred in transduced SMC, compared with nontransduced or MFG-lac Z-transduced cells (p < 0.05). PAI-1 antigen was unchanged in transduced SMC but decreased in MFG-tPA transduced EC (p < 0.05). PAI-1 mRNA was unchanged in the transduced EC and SMC compared with nontransduced cells, suggesting that posttranslational events may have caused the changes in EC PAI-1. CONCLUSIONS: This investigation demonstrated that MFG-mediated tPA gene transfer into human EC resulted in a significant increase in tPA activity. Enhancement of adult human EC fibrinolytic activity by transfer of the human tPA gene has not been previously reported and represents a necessary finding in the development of this gene therapy technology for the prevention of thrombotic complications of vascular disease. PMID- 7776476 TI - The significance of microemboli detection by means of transcranial Doppler ultrasonography monitoring in carotid endarterectomy. AB - PURPOSE: Carotid endarterectomy (CEA) performed with continuous transcranial Doppler monitoring provides a unique opportunity to determine the number of cerebral microemboli and to relate their occurrence to the surgical technique. The purpose of this study was to assess in CEA the impact of cerebral microembolism on clinical outcome and brain architecture. We also evaluated the influence of the audible transcranial Doppler signal on the surgeon and his or her technique. METHODS: In a prospective series of 301 patients, CEA was monitored with electroencephalography and transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. Preoperative and intraoperative risk factors were entered in a logistic regression analysis program to assess their correlation with cerebral outcome. To evaluate the impact of cerebral microembolism on brain architecture, we compared preoperative and postoperative computed tomography scans or magnetic resonance images of the brain in two subgroups of 58 and 40 patients, respectively. RESULTS: Seven (2.3%) patients had intraoperative transient ischemic symptoms, three (1%) had intraoperative strokes, 1 (0.3%) had transient ischemic symptoms after operation, and 10 (3.3%) had postoperative strokes. Four (1.3%) patients died. Microemboli (> 10) noticed during dissection were related to both intraoperative (p < 0.002) and postoperative (p < 0.02) cerebral complications. Microemboli that occurred during shunting were also related to intraoperative complications (p < 0.007). Microembolism never resulted in new morphologic changes on postoperative computed tomography scans. On the contrary, the phenomenon of more than 10 microemboli during dissection was significantly (p < 0.005) related to new hyperintense lesions on postoperative T2-weighted magnetic resonance images. CONCLUSIONS: During CEA the presence of microembolism (> 10 microemboli) during dissection shows a statistically significant relationship with perioperative cerebral complications and with new ischemic lesions on magnetic resonance images of the brain. Moreover, microembolism during shunting is also related to intraoperative complications. Surgeons can be guided by the audio Doppler and emboli signals by changing their technique. This change may result in a decrease of microembolism and consequently in a decline of the intraoperative stroke rate. PMID- 7776477 TI - Spinal cord protection during thoracoabdominal aortic aneurysm repair: results of selective reconstruction of the critical segmental arteries guided by evoked spinal cord potential monitoring. AB - PURPOSE: The purpose of this study is to evaluate the results of spinal cord protection based on selective reconstruction of the segmental arteries. METHODS: Twenty-one patients who underwent repair of aneurysms (nine descending thoracic and 12 thoracoabdominal: three type I, six type II, and three type III) were analyzed. Ten patients had postdissection aneurysms. Operative techniques consisted of evoked spinal cord potential (ESP-dsc) monitoring and femorofemoral bypass in all cases, segmental resection in 12, and mild systemic hypothermia in eight. Arteries critical for cord blood flow were selectively reconstructed; if ESP-dsc showed change after resection of an aortic segment, arteries originating from this segment were reconstructed. RESULTS: ESP-dsc change was observed in 12 patients. Arteries found to be critical were at the T8-L1 level in all but three cases. Selective reconstruction was performed in 10 of these 12 patients. ESP-dsc change could be reversed before reconstruction in four cases, three by control of back-bleeding critical arteries. Selective reconstruction resulted in return of ESP-dsc in seven other patients. Spinal cord injury occurred in five patients, two of whom did not undergo selective reconstruction. CONCLUSION: These results suggest that our current technique allows determination of critical arteries but does not completely prevent injury. PMID- 7776479 TI - Ruptured thoracic aortic aneurysms: a study of incidence and mortality rates. AB - PURPOSE: The purpose of this study was to determine the incidence and mortality rate of ruptured thoracic aortic aneurysm (TAA) in a well-defined population. METHODS: Retrospective analysis of complied data from multiple registries in Stockholm, Sweden was performed. RESULTS: Eighty-two and 76 cases were identified from 1980 and 1989, respectively, for an equal incidence of 5 per 100,000. Forty one percent of the patients were alive on arrival at an emergency hospital, but the overall mortality rate was 97% to 100%. CONCLUSIONS: The mortality rate of ruptured TAA is high. To decrease this high mortality rate, efficient screening methods for the diagnosis of TAA must be worked out, characteristics indicating high risk of rupture must be identified, and efforts should be made to increase the number of operations for ruptured TAA. PMID- 7776478 TI - Determining the acuteness and stability of deep venous thrombosis by ultrasonic tissue characterization. AB - PURPOSE: The intent of the study was to determine whether ultrasonic tissue characterization (UTC) could indicate acuteness and stability of deep venous thrombosis (DVT) of the lower extremities. METHODS: Thrombi presenting as filling defects on color Doppler imaging in the common or superficial femoral or popliteal veins in 50 extremities in 45 patients with DVT were studied. Acute DVT was less than 4 days duration, and chronic DVT was greater than 21 days duration. UTC analysis of parameters from the normalized power spectrum of backscattered ultrasound signals from venous filling defects was performed. This spectrum approaches a straight line, and its basic parameters, slope, and Y-intercept are related to scatterer size, concentration, and the square of the scatterer-to medium acoustic impedances. Ten of the DVT extremities were reexamined at 1 week to assess UTC changes that would indicate thrombus instability. RESULTS: Acute DVT (19 of the 50 extremities) could be distinguished from chronic DVT, mainly on the basis of significantly higher intercept values for the acute group, which were 11.6 relative decibels (dBr) higher than those of the chronic DVT group. Discriminant linear analysis of the two parameters indicated a sensitivity of 94.7% and specificity of 90.3% in correctly diagnosing acute DVT. In a small sample of 10 extremities reexamined at 1 week, acute DVT extremities showed a mean 9.4 dBr decrease in intercept values with no significant change in slope. CONCLUSIONS: UTC distinguished clinically defined acute from chronic DVT. In a small series of extremities, UTC revealed significant instability of acute thrombi in a selected patient population. PMID- 7776480 TI - Screening for asymptomatic internal carotid artery stenosis: duplex criteria for discriminating 60% to 99% stenosis. AB - PURPOSE: The Asymptomatic Carotid Atherosclerosis Study (ACAS) showed that carotid endarterectomy reduces stroke risk in symptom-free patients with 60% or greater internal carotid artery (ICA) stenosis. This will surely lead to the performance of an increased number of screening duplex examinations. Assuming that positive study results will lead to arteriography or endarterectomy and keeping in mind the modest benefit for prophylactic endarterectomy demonstrated by ACAS (absolute risk reduction for ipsilateral stroke of 5.8% at 5 years), duplex criteria for 60% or greater ICA stenosis must have high positive predictive values (PPV). Determining criteria for 60% or greater stenosis, which emphasized high accuracy and PPV, forms the basis for this study. METHODS: Stenoses detected by angiography in 352 ICAs were blindly compared with those detected by duplex scanning. Duplex criteria were determined for highest overall accuracy in detection of 60% or greater ICA stenosis and for 95% or greater PPV. RESULTS: Maximal accuracy for detection of 60% or greater stenosis was 90%. This was achieved by the combination of a peak systolic velocity of 260 cm/sec or greater and an end diastolic velocity of 70 cm/sec or greater (sensitivity 84%, specificity 94%, PPV 92%). The 95% PPV for 60% or greater stenosis results from combining peak systolic velocity of 290 cm/sec or greater and end diastolic velocity of 80 cm/sec or greater. CONCLUSIONS: With use of these criteria duplex scanning accurately detects with high PPVs the threshold level of ICA stenosis defined in ACAS as receiving stroke reduction benefit from prophylactic carotid endarterectomy. These criteria should be useful for carotid artery screening and minimizing unneeded intervention. PMID- 7776481 TI - Endovascular arterial intervention: expression of concern. PMID- 7776482 TI - Treatment options for phlegmasia cerulea dolens. PMID- 7776483 TI - A case report of inflammatory aneurysm of the thoracic aorta. PMID- 7776484 TI - A piece of my mind. A trial for my life. PMID- 7776485 TI - Terms of engraftment: umbilical cord blood transplants arouse enthusiasm. PMID- 7776486 TI - FDA pushes for prescription drug information. PMID- 7776487 TI - From the Veterans Health Administration. PMID- 7776488 TI - From the Centers for Disease Control and Prevention. Update: trends in AIDS among men who have sex with men--United States, 1989-1994. PMID- 7776489 TI - From the Centers for Disease Control and Prevention. Prevalence and impact of arthritis among women--United States, 1989-1991. PMID- 7776490 TI - From the Centers for Disease Control and Prevention. Cholera associated with food transported from El Salvador--Indiana, 1994. PMID- 7776491 TI - Diagnostic and therapeutic technology assessment. Transjugular intrahepatic portosystemic shunt (TIPS). AB - OBJECTIVE: To provide clinicians with a technology assessment of the safety and effectiveness of the use of a transjugular intrahepatic portosystemic shunt (TIPS) for reducing portal hypertension and its associated complications of esophageal varices and ascites. PARTICIPANTS: A literature review and a Diagnostic and Therapeutic Technology Assessment (DATTA) survey questionnaire were mailed to 72 physicians with expertise in gastrointestinal or abdominal surgery or interventional radiology and a special interest in liver disease or esophageal varices. These panelists had been nominated to the DATTA panel by appropriate specialty societies and medical schools. A total of 54 panelists (75%) responded. EVIDENCE: Assessment was based on the expert opinion of the panelists, as well as on published scientific literature (available as of January 2, 1995). Published studies were identified by a MEDLINE search using the terms transjugular intrahepatic portosystemic shunt, TIPS, and transjugular and by review of the references cited in these primary sources. CONSENSUS PROCESS: The respondents completed a DATTA survey questionnaire; the survey results were tabulated, analyzed, and interpreted by an American Medical Association staff physician. CONCLUSIONS: The safety of TIPS was considered to be established in the acute control of bleeding from esophageal varices in patients who had failed sclerotherapy. The safety of TIPS was considered to be promising for long-term control of bleeding from esophageal varices. In patients with end-stage liver disease and esophageal varices who are liver transplant candidates, the use of TIPS was considered to be an established therapy. The effectiveness of TIPS was considered to be (1) established in the acute control of bleeding in patients who failed sclerotherapy; (2) promising for long-term control of bleeding from esophageal varices; and (3) established in patients with end-stage liver disease and esophageal varices who are candidates for liver transplants. PMID- 7776492 TI - Captopril and diabetic nephropathy. PMID- 7776493 TI - HIV incidence among injection drug users enrolled in a Los Angeles methadone program. PMID- 7776494 TI - In the wake of Hurricane Andrew. PMID- 7776495 TI - Cost-effective treatment of depression. PMID- 7776496 TI - Dietary carotenoids, vitamins A, C, and E, and macular degeneration. PMID- 7776497 TI - Intramuscular vs intradermal hepatitis B vaccination: a 6-year follow-up. PMID- 7776498 TI - Lipoproteins, coagulation states, and risk of thrombotic events. PMID- 7776499 TI - Cost of patient follow-up after potentially curative colorectal cancer treatment. AB - OBJECTIVE: To estimate the cost of follow-up among colorectal cancer patients treated with curative intent based on the broad spectrum of surveillance strategies suggested in the literature. DESIGN: Economic analysis of the costs associated with 11 separate surveillance strategies. Charge data were obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Medicare-allowed charges and an actual-charge proxy for 5 years of follow-up after treatment for colorectal cancer patients on a nationwide basis. RESULTS: Medicare-allowed charges varied widely for the 5 years of posttreatment follow-up from a low of $561 to a high of $16,492. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $910 to $26,717, a 28 fold difference in charges. CONCLUSIONS: Charges vary extensively across follow up strategies, with no indication that higher-cost strategies increase survival or quality of life. PMID- 7776500 TI - Identification of comatose patients at high risk for death or severe disability. SUPPORT Investigators. Understand Prognoses and Preferences for Outcomes and Risks of Treatments. AB - OBJECTIVE: To develop and validate a simple prognostic scoring system to identify patients in nontraumatic coma at high risk for poor outcomes using data available early in the hospital course. DESIGN: Prospective cohort study. SETTING: Five geographically diverse academic medical centers. PATIENTS: A total of 596 patients in nontraumatic coma enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), including 247 in the model derivation set and 349 in the model validation set. MAIN OUTCOME MEASURES: Death and severe disability by 2 months. MAIN RESULTS: For the 596 patients studied (median age, 67 years; 52% female), the primary cause of coma was cardiac arrest in 31% and cerebral infarction or intracerebral hemorrhage in 36%. At 2 months 69% had died, 20% had survived with known severe disability, 8% were known to have survived without severe disability, and 3% survived with unknown functional status. Five clinical variables available on day 3 after enrollment were associated independently with 2-month mortality: abnormal brain stem response (adjusted odds ratio [OR] = 3.2; 95% confidence interval [CI], 1.3 to 8.1), absent verbal response (OR = 4.6; 95% CI, 1.8 to 11.7), absent withdrawal response to pain (OR = 4.3; 95% CI, 1.7 to 10.8), creatinine level greater than or equal to 132.6 mumol/L (1.5 mg/dL) (OR = 4.5; 95% CI, 1.8 to 11.0), and age of 70 years or older (OR = 5.1; 95% CI, 2.2 to 12.2). Mortality at 2 months for patients with four or five of these risk factors was 97% (58/60; 95% CI, 88% to 100%) in the validation set. Brain stem and motor responses best predicted death or severe disability by 2 months. For patients with either an abnormal brain stem response or absent motor response to pain, the rate of death or severe disability at 2 months was 96% (185/193; 95% CI, 92% to 98%) in the validation set. CONCLUSIONS: Five readily available clinical variables identify a large subgroup of patients in nontraumatic coma at high risk for poor outcomes. This risk stratification approach offers physicians, patients, and patients' families information that may prove useful in patient care decisions and resource allocation. PMID- 7776501 TI - Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. AB - OBJECTIVE: To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease. DESIGN: A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol niacin on coronary artery disease progression. SETTING: Community- and university based cardiac catheterization laboratories. SUBJECTS: A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION: Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized). OUTCOME: Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S). RESULTS: Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS: These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed. PMID- 7776503 TI - Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy. AB - OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) in an outbreak among patients receiving home intravenous infusion therapy. DESIGN: Case control and retrospective cohort studies. SETTING: Home health agency. PATIENTS: Patients receiving home intravenous infusion therapy from Rhode Island Home Therapeutics (RIHT) from January through December 1993. MAIN OUTCOME MEASURE: Development of primary BSI. METHODS: We compared patients with BSI (ie, case patients) with randomly selected noninfected RIHT patients receiving intravenous therapy, conducted a cohort study of all RIHT patients receiving intravenous therapy via a central venous catheter (CVC), and conducted a culture survey of injection cap luminal fluid. RESULTS: Case patients were more likely than controls to have had therapy via a CVC (11/11 vs 14/32; odds ratio [OR] undefined; P < .001) or total parenteral nutrition and intralipid therapy (TPN/IL) (9/11 vs 3/32; OR, 43.5; 95% confidence interval [CI], 4.9 to 510.0). Among RIHT patients with CVCs, risk factors for BSI were receipt of TPN/IL (9/35 vs 2/67; rate ratio [RR], 8.6; 95% CI, 2.0 to 37.7) or use of a needleless infusion system (10/41 vs 1/61; RR, 14.9; 95% CI, 2.0 to 111.8). Only the combination of both exposures was significantly associated with development of a BSI (P < .001). Luminal fluid from injection caps of needleless devices was significantly more likely to be culture positive than fluid from protected-needle devices (5/23 vs 0/18; RR undefined; P = .04). CONCLUSIONS: Our data suggest that a needleless device used for TPN/IL was associated with increased risk of BSI when injection caps were changed every 7 days. PMID- 7776504 TI - Recommendations for off-label use of intravenously administered immunoglobulin preparations. University Hospital Consortium Expert Panel for Off-Label Use of Polyvalent Intravenously Administered Immunoglobulin Preparations. AB - OBJECTIVE: To summarize consensus recommendations for off-label uses of standard intravenous immunoglobulin (IVIG), as developed by a University Hospital Consortium (UHC) Expert Panel. These findings are intended to help guide clinicians in the appropriate and efficient use of IVIG. PARTICIPANTS: The UHC sponsored panel included eight physicians (board certified in critical care, hematology, immunology, neurology, oncology, pediatrics, or rheumatology) and two hospital pharmacists. EVIDENCE: MEDLINE and EMBASE were searched to identify all English-language review articles (n = 201) and original reports (n = 1904) on IVIG (human use only, excluding editorials, letters, and comments) published between January 1982 and March 1994. Relevant original reports (250) and review articles (87) were evaluated by the first author (T.A.R.). Extracted data included laboratory and clinical findings, objective measures, or clinical impressions. The evidence quality was graded by study design according to the US Preventive Services Task Force. CONSENSUS PROCESS: Before the panel meeting, a draft literature review and recommendations were produced by one of the authors (T.A.R.). The recommendations herein represent consensus (100% agreement) based on the published evidence. CONCLUSIONS: The UHC Expert Panel made specific recommendations for 53 off-label indications and the following general recommendations: (1) Usually IVIG is indicated only if standard approaches have failed, become intolerable, or are contraindicated; (2) IVIG products should be considered therapeutically equivalent and interchangeable; (3) interproduct pharmaceutical differences should be considered with the patient's clinical and physiological status when selecting an IVIG product; and (4) currently, IVIG manufacturers cannot guarantee freedom from viral contamination in the finished product. PMID- 7776502 TI - Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. AB - OBJECTIVE: To test the hypothesis that insulin resistance precedes impaired insulin secretion in individuals genetically predisposed to non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: Case-control study. SETTING: Outpatient facility of clinical research center. PARTICIPANTS: One hundred volunteers of European ancestry having normal glucose tolerance, 50 with and 50 without a first degree NIDDM relative, matched for age, sex, and degree of obesity. MAIN OUTCOME MEASURES: Insulin secretion and insulin sensitivity assessed by hyperglycemic (N = 100) and euglycemic-hyperinsulinemic (N = 62) clamp experiments. RESULTS: The individuals with a first-degree NIDDM relative had reduced first- and second phase insulin responses (mean +/- SEM, 939 +/- 68 vs 1209 +/- 82 pmol/L, and 322 +/- 19 vs 407 +/- 24 pmol/L, respectively, P = .001 and .01), but their insulin sensitivity (148 +/- 6 and 92 +/- 6 nmol.kg-1.min-1/pmol.L-1 in hyperglycemic and euglycemic clamp studies) did not differ from that of the control group (126 +/- 5 and 81 +/- 7 nmol.kg-1.min-1/pmol.L-1, in hyperglycemic and euglycemic clamp studies, P = .07 and .24, respectively). In some individuals only first- or only second-phase insulin responses were reduced. CONCLUSION: In this study population, heterogeneous defects in insulin secretion were demonstrated, while defects in insulin sensitivity were not evident. We therefore conclude that since the earliest defects identified in a group genetically at high risk to develop NIDDM are those related to insulin secretion, defects in insulin secretion rather than insulin sensitivity are likely the major genetic factor predisposing to development of NIDDM. PMID- 7776505 TI - Attention-deficit disorder. Born to be hyperactive? PMID- 7776507 TI - Follow-up testing for curatively treated cancer survivors. What to do? PMID- 7776508 TI - Which comes first in non-insulin-dependent diabetes mellitus: insulin resistance or beta-cell failure? Both come first. PMID- 7776506 TI - Marihuana as medicine. A plea for reconsideration. PMID- 7776509 TI - [Is there a receptor for volatile anesthetics?]. AB - Because of the presence of inequality of the effect of volatile anesthetics on various neurotransmission systems, a specific receptor is proposed. Nonetheless, the differences are only of the magnitude, and almost all synapses are equally affected. The outstanding features of the action of volatile anesthetics are this wide range of the target, and the steep dose-response curve. The steep dose response curve indicates that various synapses respond to anesthetics with high cooperativity. When a string of amino acids folds into biologically meaningful structure by enclosing hydrophobic areas inside, some hydrophobic parts are left at the protein-water interface. These hydrophobic patches become the binding site for anesthetics. Because of the wide difference in the structures of anesthetics, it is difficult to assume a specific binding site of lock-and-key type for all anesthetics with all synaptic proteins. Presumably volatile anesthetics bind most hydrophobic patches nonselectively. The affinity to each patch may differ, and the relative specificity to each synapse may ensue. To define these areas as a receptor is a matter of opinion. PMID- 7776510 TI - [Continuous epidural buprenorphine for postoperative pain relief after thoracotomy]. AB - To evaluate postoperative analgesia and side effects of epidural buprenorphine, 60 patients after thoracotomy were divided into 6 groups. All patients received a bolus epidural administration of buprenorphine 0.1 mg in 8 ml of 0.25% bupivacaine. Following this epidural bolus, 10 patients in each group were given 0.25% bupivacaine alone (group A), buprenorphine 5 micrograms in 1 ml of 0.25% bupivacaine (group B), buprenorphine 8 micrograms in 1 ml of 0.25% bupivacaine (group C), buprenorphine 12 micrograms in 1 ml of 0.25% bupivacaine (group D), buprenorphine 15 micrograms in 1 ml of 0.25% bupivacaine (group E) or buprenorphine 18 micrograms in 1 ml of 0.25% bupivacaine (group F) with a portable disposable device at a rate of 1 ml.h-1 for 48 h. The percentages of patients who did not need additional narcotics for the first 24 hours postoperatively in group A, B, C, D, E, and F were 20%, 40%, 30%, 50%, 60%, and 70%, respectively. Those for the second 24 hours postoperatively in each group were 40%, 50%, 70%, 60%, 90%, and 90%, respectively. No significant difference in the incidence of side-effect was found among 6 groups. We concluded that optimal epidural doses of buprenorphine for post-thoracotomy pain relief are 15 and 18 micrograms.h-1 in the first and second 24 hours postoperatively, respectively. PMID- 7776511 TI - [Postoperative analgesia service by continuous epidural infusion with buprenorphine]. AB - We examined the analgesic efficacy and side effects of continuous epidural infusion with buprenorphine in 340 surgical patients. The patients received epidural injection of 0.1 mg of buprenorphine in 8 ml of 0.25% bupivacaine immediately after surgery. The patients who underwent thoracotomy or intraabdominal surgery were subsequently infused with buprenorphine 15 micrograms in 1 ml of 0.25% buprenorphine at a rate of 1 ml.h-1 for 48 h. In the other kinds of surgery, patients were infused with buprenorphine 8 micrograms in 1 ml of 0.25% buprenorphine at a rate of 1 ml.h-1 for 48 h. The patients who did not need additional narcotics were 68% and 83% on the postoperative day 1 and 2, respectively. Visual analogue scale (VAS) was 22 +/- 2 mm at rest and 43 +/- 2 mm at movement on the postoperative day 1. Corresponding values on the postoperative day 2 were 16 +/- 2 mm and 37 +/- 2 mm, respectively. Nausea and vomiting were found in 12.4% of the patients. PMID- 7776512 TI - [Neonatal apnea after general anesthesia--effects of intraoperative hyperventilation and serum ionized Ca concentration]. AB - The relationship between neonatal apnea following general anesthesia and serum ionized calcium (Ca2+) concentration was examined in 13 neonates who had received intraoperative hyperventilation. In all cases, preoperative serum Ca2+ concentration was within normal limits. The anesthesia was maintained by nitrous oxide and oxygen. At the end of anesthesia, the incidence of abnormal breathing such as apnea, periodic breathing or subcostal retraction and their activity were investigated. Five minutes after intravenous administration of 2% CaCl2 solution (16 mg.kg-1), the same parameters were compared with the values before CaCl2 administration. As we used only Ca2+ free solution for fluid therapy during operation, serum Ca2+ concentration decreased gradually under general anesthesia, but after CaCl2 administration, it increased and the incidence of abnormal breathing decreased. To determine the relationship between hyperventilation and the incidence of abnormal breathing, the data were analyzed by dividing the patients into two groups based on PaCO2 level, a lower PaCO2 group (intraoperative PaCO2 < 30 mmHg, n = 5) and a higher PaCO2 group (PaCO2 > or = 30 mmHg, n = 8). But there was no significant relationship between them. In conclusion, this study demonstrates that the Ca administration has a favorable effect on respiratory system and motor activity, but we cannot relate the incidence of postoperative abnormal breathing to the degree of hyperventilation. PMID- 7776513 TI - [Diltiazem potentiates the neuromuscular blockade by vecuronium in humans]. AB - We investigated interaction of diltiazem with vecuronium using constant infusion technique in 24 ASA class I or II elective surgical patients with no preoperative administration of Ca antagonists. Neuromuscular blockade was evaluated with accelerometry, which measured single twitch height of adductor pollicis muscle. After tracheal intubation under isoflurane anesthesia, patients received either no diltiazem (control group, n = 8)m, 5 mg (bolus) + 2 mcg.kg-1.min-1 constant infusion (2 mcg group, n = 8) or 5 mg (bolus) + 4 mcg.kg-1.min-1 constant infusion (4 mcg group, n = 8). When single twitch height returned to 10% of control value, infusion of vecuronium was started and the infusion rate was adjusted to maintain twitch height at 10% of the control value. After 30 minutes of stable twitch height, the vecuronium infusion rate and plasma diltiazem concentrations were measured. Diltiazem infusion of 4 mcg.kg-1.min-1 decreased the vecuronium infusion rate by 45% compared with 2 other groups. Plasma diltiazem concentrations in patients receiving 4 mcg.kg-1.min-1 were significantly higher than those receiving 2 mcg.kg-1.min-1. In conclusion diltiazem 4 mcg.kg-1.min-1 potentiates the neuromuscular blockade of vecuronium and it relates with the plasma diltiazem concentration. PMID- 7776515 TI - [Effects of trimetaphan on hemodynamics and pulmonary gas exchange--a comparison with those of nitroglycerin and prostaglandin E1]. AB - In recent studies, the changes in arterial and end-tidal carbon dioxide tensions have been shown to correlate linearly with changes in cardiac output during the constant minute ventilation. High and low ventilation to perfusion ratios can also be estimated from blood and expiratory gas analysis. In the present study, the effects of trimetaphan (29 +/- 3 micrograms.kg-1.min-1) on hemodynamics and pulmonary gas exchanges were studied by analyzing these gas tensions in nine sevoflurane/nitrous oxide anesthetized patients, and were compared with those of nitroglycerin (5 micrograms.kg-1.min-1) and prostaglandin E1 (100 ng.kg-1.min-1) which had been reported in the previous study. During trimetaphan administration, arterial pressure decreased. The decreases in both systolic and diastolic arterial pressures were greater than those during nitroglycerin or prostaglandin E1 administration. PaCO2 decreased significantly, whereas it did not change in fixed direction with nitroglycerin infusion and increased with prostaglandin E1 infusion. The magnification of both alveolar-arterial oxygen tension difference and arterial-end-tidal carbon dioxide tension difference during trimetaphan administration was equal to that during prostaglandin E1 administration and smaller than that during nitroglycerin administration. Therefore, it seems that trimetaphan as well as nitroglycerin decreases cardiac output but prostaglandin E1 increases or maintains it in patients under sevoflurane/nitrous oxide anesthesia, that trimetaphan reduces vascular resistance most weakly of the three (trimetaphan < nitroglycerin < prostaglandin E1), and that trimetaphan as well as prostaglandin E1 does not influence pulmonary blood distribution as strongly as nitroglycerin. PMID- 7776514 TI - [Estimation of respiratory functions by analysis of expired gas and blood gas during artificial ventilation and general anesthesia]. AB - One-hundred and seven patients undergoing elective surgery were studied to analyze the correlations between preoperative spirometric values and respiratory parameters during general anesthesia. They were grouped according to 3 criterions; preoperative %VC of less than 80%, FEV1.0% of less than 70%, V50/V25 exceeding 4.0. Following the induction of general anesthesia and of mechanical ventilation, expiratory flow (VE), FECO2, PaCO2 and PaO2 were measured to calculate respiratory parameters including VCO2-SR, VD/VT-Bohr, VD/VT physiological (phys), a-ETDCO2, Volume Pressure Index (VPI) and A-aDO2. Six respiratory parameters were compared between the groups, and correlations between preoperative spirometric values were studied. Those with lower %VC had higher values in VCO2-SR and in VPI, and those with lower FEV1.0% had higher values in VCO2-SR, in VD/VT-phys and in a-ETDCO2. Significant correlations were also observed between these parameters. Preoperative V50/V25 and A-aDO2 during general anesthesia did not correlate with any of the parameters studied. We conclude that VCO2-SR, VD/VT-phys, a-ETDCO2 and VPI during general anesthesia are useful to detect the patients with restrictive and/or obstructive lung dysfunction, although they are not sensitive enough to detect those with small airway disease. PMID- 7776516 TI - [The comparison of hypnotic potency of nitrous oxide with that of sevoflurane: evaluation by the middle latency auditory evoked response]. AB - In 10 consented patients (ASA I-II) we quantitated the hypnotic potencies of 0.7 MAC nitrous oxide and 0.7 MAC sevoflurane by measuring auditory evoked response (AER), and compared the hypnotic potency of nitrous oxide with that of sevoflurane at the same MAC. In each patient, measurements of AER waves were performed in the following three stages, 0.7 MAC nitrous oxide, 0.7 MAC sevoflurane and 0.7 MAC nitrous oxide after induction of anesthesia. Analysis of variance was used to compare the hypnotic potencies between two inhaled anesthetics. Pa and Nb latencies with sevoflurane were longer than those with nitrous oxide, and Pa and Nb amplitudes with sevoflurane were greater than those with nitrous oxide. However, we found that there were no statistical significances in our results. In conclusion, nitrous oxide exerts as much hypnotic effect as sevoflurane. PMID- 7776517 TI - [The evaluation of cuff-occluded rate of rise of peripheral venous pressure (CORRP) for monitoring blood volume status]. AB - Cuff-occluded rate of rise of peripheral venous pressure (CORRP) was evaluated for perioperative monitoring. We investigated the CORRP in 6 patients undergoing open laparotomy. These patients were given general anesthesia, and monitoring lines were inserted. Heart rate, blood pressure (BP), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP), cardiac output (CO) and CORRP were monitored. CORRP is defined as the average rate (in millimeters of mercury per minute) of rise of peripheral venous pressure after proximal occlusion of that vein by a tourniquet (select pressure: 50 mmHg). In the actual measurement of CORRP, only the first 90% of the curve after occlusion of the tourniquet is used. CORRP correlated with RAP (r = 0.69 +/ 0.10), and PCWP (r = 0.79 +/- 0.07). On the other hand, there was no significant correlation between CORRP and BP, or PAP and CO. Snyder et al. described that CORRP seems to be an excellent indicator of acute volume change in the hyper- and hypovolemic canine model. We conclude that in these laparotomy patients, CORRP appears to be a sensitive and minimally invasive method of assessing volume status. PMID- 7776518 TI - [Endocrine effects of nicardipine on intraoperative hypertension under droperidol fentanyl-ketamine (DFK) anesthesia]. AB - Effects of nicardipine on endocrine functions were evaluated in 10 surgical patients who received surgeries under total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Plasma levels of norepinephrine (NE), epinephrine (E), plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (hANP) were measured following nicardipine injection during 30 minutes of intraoperative hypertension. When the systemic blood pressure exceeded 160 mmHg systolic and 95 mmHg diastolic for five minutes, 0.5 mg approximately 10 mg of nicardipine was administered for 30 minutes to maintain the systolic blood pressure below 160 mmHg. Following the injection of nicardipine a significant reduction by 20% in the mean systolic and diastolic pressure was observed. Mean heart rate increased by 5%, but the increase was not significant. Plasma NE increased significantly 1.7 time from the control level at 15 minute following the injection. Plasma levels of E, PRA, aldosterone and hANP showed no significant changes. PMID- 7776519 TI - [The intrapulmonary metabolism of prostaglandin E1 in patients with pulmonary hypertension]. AB - We investigated the intrapulmonary metabolism of prostaglandin E1 (PGE1), hemodynamics, oxygenation indexes (OI) and intrapulmonary shunt ratios (QS/QT) in patients with pulmonary hypertension (PH group, n = 7) and those with normal pulmonary artery pressure (N group, n = 5). PGE1 at a concentration of 20 approximately 60 ng.kg-1.min-1 was continuously administered intravenously to the patients in both groups for treatment. The intrapulmonary metabolism of PGE1 was calculated as 100 x (1--the concentration ratio of PGE1 in radial/pulmonary artery) %. The concentrations of PGE1 were measured by radioimmunoassay (DCC method) with the specific anti-PGE1 antibodies supplied by Ono Pharmaceutical Co. Hemodynamics were measured using a Swan-Ganz catheter, and OI and QS/QT were calculated from blood gas analyses. In the PH group, the intrapulmonary metabolisms of PGE1 decreased significantly compared with the N group. In addition, mPAP/mSAP in the PH group increased significantly compared with the N group regardless of PGE1 administration. There were no significant differences in OI and QS/QT between the two groups in spite of PGE1 administration. We concluded that the intrapulmonary metabolisms of PGE1 in patients with pulmonary hypertension were significantly decreased compared to the patients with normal pulmonary artery pressure. For this reason, it is important to monitor hypotension more carefully whenever we administer PGE1 to patients for the treatment of pulmonary hypertension. PMID- 7776520 TI - [Effect of halothane on the energy metabolism of isolated perfused rat kidney as analysed by 31P-NMR]. AB - The effects of halothane on energy metabolism of isolated perfused rat kidney were studied by 31P-NMR spectroscopy. Rat kidney was perfused by physiological medium containing halothane. Perfusion was carried out continuously in addition to ischemic period of 30 or 10 minutes. In continuous perfusion study, halothane concentration below 4% did not affect renal ATP level but halothane above 6% decreased ATP level significantly. In ischemic study, changes of renal energy metabolism were not influenced by halothane below 4% throughout the experiment, but halothane above 6% decreased ATP levels significantly after reperfusion. From the viewpoint of energy metabolism, it can be said that a low concentration of halothane does not damage renal cells but a high concentration of halothane has possibility to damage them. During and after ischemic insult, halothane does not diminish renal damage, but on the contrary a high concentration of halothane reversely worsens it. PMID- 7776521 TI - [Pediatric anesthesia and stress response]. AB - The hyperglycemic and adrenocortical responses to upper and lower abdominal surgery were studied in four groups of children. In F group, lower abdominal surgery was performed under light general anesthesia (halothane 0.3-0.5% plus nitrous oxide and oxygen) combined with intravenous injections of fentanyl 10-13 micrograms.kg-1. In L-E group, lower abdominal surgery was performed under light general anesthesia combined with lumbar epidural anesthesia (intermittent injections of 1.0% lidocaine). In T-E group, upper abdominal surgery was performed under light general anesthesia combined with thoracic epidural anesthesia (intermittent injections of 1.0% lidocaine). In H group, lower abdominal surgery was performed under general anesthesia (halothane 1.0-1.5% plus nitrous oxide and oxygen). The hyperglycemic and adrenocortical responses were inhibited in F group, suggesting that intravenous injections of fentanyl 10-13 micrograms.kg-1 prevented the endocrine-metabolic response. On the other hand, in other three groups, those responses were not inhibited. Therefore we must consider the concentration and the volume of lidocaine in epidural groups. But general anesthesia combined with epidural anesthesia had a excellent effect on the postoperative pain management. PMID- 7776522 TI - [Anesthesia for a patient with Creutzfeldt-Jakob disease]. AB - We reported anesthetic as well as perioperative management for a patient with Creutzfeldt-Jakob disease, a very rare transmissible neuropathy. A 51 year-old woman was scheduled for extirpation of recurrence of acoustic neurinoma. Three months before the operation, she had complained vertigo. After admission to our hospital, she had become progressively dementiated and developed disturbed consciousness. Anesthesia was induced with thiamylal and maintained with 0.7-1.5% isoflurane, nitrous oxide and oxygen. The anesthetic course was uneventful and the recovery from anesthesia was smooth. Postoperatively dementia progressed and myoclonus of extremeties appeared sixth weeks after the operation. Two months after the operation, a diagnosis of Creutzfeldt-Jakob disease was established by characteristic EEG and clinical course. Anesthesia for a patient with dementia was discussed. PMID- 7776524 TI - [Spinal anesthesia for an emergency surgery in a patient with right sided heart failure]. AB - A 79-year-old female with a pace maker implanted because of complete A-V block associated with right sided heart failure was scheduled for the emergency repair of incarcerated abdominal wall hernia. Spinal anesthesia for the surgery and epidural catheterization for postoperative pain control were performed. Anesthesia and postoperative course were uneventful. The effects of spinal anesthesia on cardiovascular system are the result of preganglionic sympathetic block produced by the local anesthetic agent injected in the subarachnoid space. It is, therefore, desirable to consider the cardiovascular effects of spinal anesthesia (reduction of afterload and preload) on a patient who has right sided heart failure. Post operative pain control by PCA pump is also a basic method for a patient with right sided heart failure. PMID- 7776523 TI - [Spinal anesthesia for oophorectomy in a patient with pulmonary lymphangiomyomatosis accompanied by hypochondriasis]. AB - A 41-year-old woman with pulmonary lymphangiomyomatosis had been scheduled for bilateral oophorectomy which led to amelioration of the pulmonary pathology. The discrepancy between her dyspnea on exertion and lung function tests suggested that she had a marked tendency toward hypochondria. Therefore, we chose spinal anesthesia because of its technical simplicity, rapid onset, and effectiveness of some sedatives used perioperatively. Surgery was performed uneventfully. The anesthetic method mentioned above did not worsen respiratory function perioperatively. Spinal anesthesia is thought to be appropriate anesthesia for patients with pulmonary lymphangiomyomatosis, if feasible. PMID- 7776525 TI - [The support of postoperative renal function by ulinastatin in patients with preoperative renal dysfunction]. AB - The principal perioperative management of patients with renal dysfunction is to prevent postoperative acute renal failure. Therefore, it is crucial to do all possible therapies by which its occurrence is prevented. We experienced three cases in which ulinastatin may have been beneficial to maintain postoperative renal function. The patients had preoperative renal dysfunction with serum Cr between 1.5 and 2.0 mg.dl-1. During the operation and for the three postoperative days, 300,000 units.day-1 of ulinastatin were administered intravenously. After the operation, serum Cr level was not elevated. Urine output and creatinine clearance increased. These three clinical cases suggest that ulinastatin may prevent the deterioration of postoperative renal function in patient with preoperative renal dysfunction. PMID- 7776526 TI - [Anesthetic management using percutaneous cardiopulmonary support for cesarean section in a patient with severe pulmonary hypertension]. AB - A 27-year-old female with severe pulmonary hypertension was scheduled to undergo an elective cesarean section at the 32-week gestational age. Since the preoperative assessment revealed that the patient could not tolerate the hemodynamic changes during the operation under general anesthesia without any cardiopulmonary support, the percutaneous cardiopulmonary support (PCPS) with a centrifugal pump was applied for the anesthetic management of the patient during the operation. After the induction of anesthesia, percutaneous cannulation was performed via the femoral artery and vein, and the PCPS was started with an assisted flow ranged 1.5-2.0 l.min-1. Then, the operation was performed, during which the cardiopulmonary function of the patient was well maintained with the aid of the PCPS. The operation was finished uneventfully, and the patient could successfully emerge from the PCPS immediately after the operation. The PCPS is thought to be very useful for the anesthetic management of the patients with poor cardiopulmonary tolerance. PMID- 7776527 TI - [Lack of effect of i.v. lidocaine on cardiovascular responses to laryngoscopy and intubation]. AB - A randomized open study was carried out on 36, ASA I-II adult surgical patients to assess the effect of intravenous lidocaine and fentanyl on circulatory responses to laryngoscopy and intubation. The three treatment groups include: group L, intravenous lidocaine 1.5 mg.kg-1 2 minutes before laryngoscopy, group F, intravenous fentanyl 4 micrograms.kg-1, and group C, no treatment. Induction, preceded by preoxygenation was performed by intravenous vecuronium for precurarisation, followed by thiopental 4-5 micrograms.kg-1 and succinylcholine 1.5 mg.kg-1. Before induction of anesthesia, there were no significant differences among the three groups in mean arterial pressure (MAP), heart rate (HR) and rate pressure product (RPP). After laryngoscopy and intubation, the three hemodynamic variables increased significantly from control values in group L and group C. The maximum values attained after intubation did not differ significantly between the two groups for any of the variables. In group F, these hemodynamic variables showed no significant changes after laryngoscopy and intubation and were significantly less than those in group F and group C. Intubating conditions were better in the fentanyl group than in the lidocaine group. PMID- 7776528 TI - [Use of ketamine combined with local anesthetics in epidural anesthesia]. AB - Postoperative pain relief and sedation with epidural ketamine were studied. Twenty-four patients for elective upper abdominal surgery were divided into 4 groups. Epidural catheter was inserted into thoracic epidural space before induction of general anesthesia. In each group, either 0.25% bupivacaine 5 ml only, ketamine 0.1 mg.kg-1 + bupivacaine 5 ml, or ketamine 0.3 mg.kg-1 + bupivacaine 5 ml, or ketamine 0.5 mg.kg-1 + bupivacaine 5 ml was injected into epidural catheter for complaint of pain in recovery room. In ketamine injected groups, blood pressure and heart were unchanged, but respiration rate increased significantly. Patients in ketamine 0.3 or 0.5 mg.kg-1 injected groups, pain relief and sedation score were significantly intensified, but patients in ketamine 0.5 mg.kg-1 injected group, incidence of pain in the back during injection and headache was high. We conclude that epidural ketamine is useful for postoperative pain relief, and the superior dose of epidural ketamine is 0.3 mg.kg-1. PMID- 7776530 TI - [Clinical evaluation of prophylactic nitroglycerin infusion during coronary artery bypass grafting]. AB - We evaluated retrospectively the benefit of prophylactic nitroglycerin (TNG) infusions during elective coronary artery bypass grafting (CABG) in 73 patients. In all patients anesthesia was maintained with high dose fentanyl. Thirty-seven patients were infused TNG 0.3 microgram.kg-1.min-1 during surgery and 36 patients were not. The TNG-infused patients demonstrated lower perfusion pressure during cardiopulmonary bypass (CPB) and higher incidence of inotropic administrations than the uninfused patients. Serum myocardial creatine phosphokinase (CPK-MB) levels of TNG-infused patients were higher than those of TNG-uninfused patients on the first postoperative day. We speculate that inotropic administrations under low myocardial perfusion pressure at the time of weaning from CPB induces myocardial ischemia which in turn causes an increase in serum CPK-MB level. We conclude that prophylactic administration of TNG does not prevent perioperative ischemia during CABG. PMID- 7776531 TI - [Experience of the great earthquake of Kobe Osaka area--role of anesthesiologists]. PMID- 7776529 TI - [Perioperative management of dialysed patients for orthopedic surgery]. AB - Recently, renal osteodystrophy is a remarkable problem in patients on long-term hemodialysis (HD). In this retrospective study, we evaluated the perioperative management of 21 patients receiving orthopedic surgery between January 1990 and December 1992. These patients had been maintained on HD for an average of 8.6 years (range, 18 months-20 years). The primary causes of orthopedic surgery were amyloidosis, diabetic gangrene, rheumatoid arthritis and fractures. Laminectomy, replacement of arthropathy, osteosynthesis and amputation of the lower extremity were undertaken. General anesthesia was performed on six patients. Vecuronium was given to all of these patients. Isoflurane was used in 5 patients and sevoflurane in 1 patient. Regional anesthesia was used in 15 patients. During anesthesia, the average infusion rate of intravenous fluids was 2.7 ml.kg-1.h-1, and the intraoperative complications included hypertension in 16, hypotension in 12, arrhythmia in 4 and prolonged sedation in 2 patients. Postoperative complications included hyperkalemia in 2, pneumonia in 2, psychological disorder in 3, clotting fistula in 1 and delayed wound healing in 7 patients. One early death in a diabetic patient following amputation occurred on the 13th postoperative day. Preoperative HD was performed within 24 hours and postoperative HD within 72 hours of the operation. Nafamostat mesilate was used as an anticoagulant. Excessive removal of potassium must be avoided during preoperative HD to prevent arrhythmia. The well-managed elective patients gave a good result. However, extreme care in nutrition and infection control should be taken, especially in diabetic patients. PMID- 7776532 TI - [An analysis of 41 elderly patients with urosepsis]. AB - We performed a clinical evaluation in 41 patients with urosepsis at Tokyo Metropolitan Geriatric Hospital from July 1992 through March 1993. The most common organism isolated from the patients was Escherichia coli (46.3%), followed by Pseudomonas aeruginosa (9.8%), Methicillin-resistant staphylococcus aureus (7.3%), and mycetes (7.3%). The most frequent underlying disease was cerebrovascular disease (34.1%) and malignancies were observed 29.2% of all cases. Twenty-six patients (63.4%) had indwelling urethral catheters. Indwelling catheters were suspected to be related to the onset of urosepsis in 16 cases. Total mortality of urosepsis was 4.9% (2/41) in this study. We speculate that the main cause of urosepsis is a long-term use of urethral catheterization, especially in elderly patients with severe complications who are vulnerable to infections. It is important to assess and correct the conditions of dysuria of individual patients before placing indwelling urethral catheters. PMID- 7776533 TI - [Factors influencing users' destination upon discharge from a geriatric intermediate care facility in an urban area]. AB - Geriatric Intermediate Care Facilities (GICF) have been established to help the hospitalized elderly return home. Users of the GICF are elderly persons who do not need hospitalization, but are mentally or physically impaired. To determine what factors influence users' destinations upon discharge from GICF, we analyzed various characteristics such as age, sex, place of residence before admission, length of stay, intellectual impairment, ability to perform activities of daily living (ADL) among users (N = 389) in a GICF in Chiba City. Multiple logistic regression analyses revealed that, compared with the users who were hospitalized, users who were male, admitted for home, stayed for long periods, and had a high ability to perform ADL were more likely to return home. The analyses also revealed that, compared with the users who were institutionalized, users who came from home, stayed for short periods, and had a high ability to perform ADL were more likely to return home. Evaluating a user's physical, mental, and socioeconomical conditions at an early stage of admission to a GICF may allow us to predict whether the user can be successfully discharged to his or her home or will have to remain at the GICF for an extended period. PMID- 7776534 TI - [Familial Alzheimer's disease in Japanese population]. AB - We ascertained 56 related cases with early onset familial Alzheimer's disease (EOFAD; mean age of onset < 65 years) and 10 related cases with late onset familial Alzheimer's disease (LOFAD; mean age of onset > or = 65 years) through a questionnaire administered to neuro-psychiatric and medical school hospitals in Japan and through a review of cases in Japanese literature. Mean age of onset and death (+/- S.D.) of EOFAD were 43.4 +/- 8.6 years (n = 94) and 51.1 +/- 10.5 years (n = 85), respectively. Distributions of the age-onset were relatively constant within a family but significantly different between families. Our result may suggest that clinical differences between families represent genetic heterogeneity at the molecular level. Six out of 32 related cases of with EOFAD showed the 717 Val-->Ile mutation of beta/A4 amyloid precursor protein (APP) gene. This result suggests that the frequency of this mutation in Japanese population is higher than in Caucasian and allelic the existenced heterogeneity, in Japanese EOFAD. PMID- 7776535 TI - [An 80-year-old female with pneumopericardium due to gastric perforation]. AB - An 80-year-old woman was admitted to our hospital because of chest oppression and general malaise. On admission, auscultation of the heart revealed friction rub, so-called water-wheel like murmur. Chest X-ray film and computed tomography showed cardiomegaly and free air in the pericardium. Electrocardiogram showed low voltage with ST elevation in II, III, aVF and V1-V4. These findings suggested that the patient had pneumopericardium with pericarditis. Wenchebach type A-V block and atrial bradycardia appeared. Thus, the ventricular pacing was performed. However, patient died of multiple organ failure. The postmortempericardiography showed the gastro-pericardial fistula with hiatus hernia. PMID- 7776536 TI - [A case of angiosarcoma with renal failure caused by recombinant interleukin-2 (rIL-2) and non-steroid anti-inflammatory drug (NSAID)]. AB - A 77-year-old man was diagnosed to have diabetes. He was hospitalized for appetite loss, weight loss (6 kg/3 months) and right femoral pain. An abnormal shadow was noted on chest X-P. On admission, he was alert and there were no abnormal physical findings except limitation in the range of motion in the right lower extremity. His femoral pain was treated by a non-steroid anti-inflammatory drug (NSAID). Right femoral bone biopsy revealed angiosarcoma and staining for factor VIII, with negative staining for epithelial membrane antigen on enzyme assay. Therefore, he received systemic administration of recombinant interleukin 2 (rIL-2). rIL-2 was administered intravenously twice daily at a dose of 40 x 10(4) JRU. The total dosage of rIL-2 amounted to 1200 x 10(4) JRU, but renal failure deteriorated and he died on the 50th hospital day of his second admission. Combination of rIL-2 and NSAID may cause progression of nephropathy. PMID- 7776537 TI - [Apolipoprotein E allele of demented and non-demented centenarians: complete survey of centenarians in Yamanashi Prefecture]. PMID- 7776538 TI - [Home oxygen therapy in elderly patients]. PMID- 7776539 TI - [Management of methicillin resistant Staphylococcus aureus in the elderly]. PMID- 7776540 TI - [The reliability and validity of a new self-completed questionnaire (QUIK)]. AB - In order to evaluate the reliability and validity of a self-completed questionnaire (QUIK), devised to measured QOL, we examined the QUIK scores of elderly who visited the Kumamoto Health Administrative Center for a medical check up in March 1994. The QUIK questionnaire, which is a close-ended and disease non specific questionnaire, covered four domains such as physical functioning, emotional adjustment, interpersonal relationships, and attitudes toward life, interacting reciprocally. The mean and standard deviation on QUIK were much better in terms of total score (5.1 +/- 5.4), for each domain score in comparison with the patient group, and even in comparison with the non-patient group. The distribution of total scores on QUIK were as follows: excellent 15%, good 35%, fair 36%, poor 11%, very poor 2% and grossly impaired 0% according to a six tiered rating scale. The internal consistency in terms of total score was alpha = 0.86. Very close correlation were seen among score, each domain score and satisfaction, being healthy and present state of feeling. If the cut-off points of total score were set between 9 and 10, the sensitivity were 0.65, specificity was 0.65 for the age index, sensitivity 1.00, validity 0.29 for the satisfaction index, while, sensitivity was 0.85 and validity 0.48, for the feeling index. There was a very close reciprocal correlation among the four domains, except for the relation between physical functioning and interpersonal relationship using multiple regression analysis. Further, significant correlations were obtained between the score in each domain and the score based on subtracting each domain score from the total score. PMID- 7776541 TI - [Value of 123I-BMIPP scintigraphy in patients with ischemic heart disease: comparison with exercise 201Tl SPECT]. AB - To evaluate 123I labeled beta-methyl-branched fatty acid (BMIPP) myocardial uptake at rest in the segment with and without stress induced ischemia in patients with coronary artery disease, 123I-beta-methyl-branched fatty acid myocardial scintigraphy was performed at rest and was compared with the findings of stress-reinjection 201Tl myocardial scintigraphy in 31 patients with coronary artery disease. In 159 ischemic myocardial segments, equally decreased uptake on both reinjection 201Tl and fatty acid images was observed in 64 segments, more severely decreased uptake of fatty acid in 76 segments, and more severely decreased uptake of reinjection thallium in 19 segments. On the other hand, in 53 non-reversible defects, each patterns was observed in 41, 3, and 9 segments respectively. When comparing the ischemic segments with more reduced uptake of fatty acid than reinjection thallium (Group 1) and the ischemic segments with equally or less reduced fatty acid uptake than reinjection thallium (Group 2), wall motion was more severely impaired in Group 1 than in Group 2 (severe hypo- to dyskinesis was present in 32 of 54 segments in group 1 and in 21 of 75 segments in group 2, p < 0.005). In conclusion, in patients with coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress induced ischemia and wall motion was more impaired in these segments. BMIPP myocardial imaging may provide information on metabolic alterations at rest independent of perfusion abnormalities in patients with coronary artery disease. PMID- 7776542 TI - [Assessment of 201Tl myocardial SPECT reinjected at 24 hours after stress imaging]. AB - To improve the quality of 24 hours delayed images (24 DL) of stress thallium-201 myocardial SPECT, reinjection was performed at 24 hours later (24 RI), and the results were compared with those of 24 DL. A total of 45 patients were studied, including 18 patients in 24 DL, 27 patients in 24 RI. All of them showed persistent defect or incomplete redistribution on the routine stress and 3 hours delayed SPECT scans. In 24 RI, 37 MBq of thallium-201 was reinjected at 24 hours later. Myocardial count of 24 DL was about 1/4 of stress image, while 24 RI was about 1/2. Quality of 24 RI image was nearly equal to 3 hours delayed image. Of regions without redistribution at 3 hours delayed image, 5 (36%) regions showed new redistribution at 24 RI. Of regions incomplete redistribution, 6 (25%) regions showed further redistribution. Compared with 24 DL, the frequency of redistribution tended to be higher in this protocol than that of the 24 DL (11%, 17% respectively). In conclusion, the reinjection at 24 hours delayed imaging was considered to be useful to evaluate viability of myocardium in patient with CAD. PMID- 7776543 TI - [Identification of viable myocardium using 99mTc-tetrofosmin scintigraphy- comparison with 201Tl redistribution-reinjection images]. AB - The purpose of this study was to clarify the diagnostic value of identifying viable myocardium using 99mTc-Tetrofosmin scintigraphy. Twenty-one patients with chronic coronary artery disease were studied using 201Tl exercise myocardial scintigraphy with reinjection and 99mTc-Tetrofosmin exercise myocardial scintigraphy. All patients had a history of old myocardial infarction. For 99mTc Tetrofosmin scintigraphy, 222 MBq of 99mTc-Tetrofosmin was injected during exercise, and exercise images were obtained 20 min thereafter. There hours later, 666 MBq of 99mTc-Tetrofosmin was injected at rest, and images were obtained 40 min and 220 min later. Myocardial viability in the 99mTc-Tetrofosmin scintigraphy was estimated as fill-in findings (FF) or over 50% of %RI uptake (%TF) in the rest image. Myocardial viability in the 201Tl scintigraphy was estimated as redistribution (RD), fill-in findings in the reinjection image (FR) or over 50% of %RI uptake in the reinjection image (% TL). Sixteen of the 21 patients (76%) who underwent 201Tl scintigraphy (RD 10, FR 3, %TL 3 cases) and 15 of the 21 patients (71%) who underwent 99mTc-Tetrofosmin scintigraphy (FF 11, %TF 4 cases) had viable myocardium in the infarcted area. A comparison between the 99mTc Tetrofosmin rest images obtained 40 min after the injection and that of 220 min revealed no redistribution findings. The %RI uptake of the infarcted area in the resting 99mTc-Tetrofosmin image (47 +/- 16%) was slightly lower than that in the 201Tl reinjection image (52 +/- 16%). In conclusion, viable myocardium was as clearly identified by 99mTc-Tetrofosmin, as by 201Tl scintigraphy. PMID- 7776544 TI - [The characteristic feature of myocardial imaging with 123I-labeled 15-(p iodophenyl)-3R,S-methylpentadecanoic acid in hypertrophic cardiomyopathy with asymmetric septal hypertrophy]. AB - The aim of this study was to elucidate the characteristic feature of myocardial imaging with 123I-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid (BMIPP) in the patients with hypertrophic cardiomyopathy (HCM). In 26 patients with asymmetric septal hypertrophy (ASH), the imaging data were acquired for 15 minutes after the injection of 123I-BMIPP by the emission computed tomography (ECT). ECT image was divided into 17 segments to score the severity of the defect in each segment using a 5-point grading system from score 3 to score -1; score 3 = severely decreased tracer uptake, score 2 = moderately decreased tracer uptake, score 1 = mildly decreased tracer uptake, score 0 = normal and score -1 = increased tracer uptake. Reduced uptake (Defect Score > or = 2) was frequently observed in septal portion of anterior wall (65%), septal portion of posterior wall (62%) and apical wall (73%). Defect score was higher in septal portion of anterior wall (p < 0.001), septal portion of posterior wall (p < 0.01) and apical wall (p < 0.01) than in the ventricular septum. This result indicates that in hearts with ASH, 123I-BMIPP image reveals severely impaired fatty acid metabolism in these regions. With the reference of the previous report about histologic features in necropsy hearts with HCM, myocardial fatty acid metabolic disorder shown by reduced 123I-BMIPP uptake is closely related to the histological abnormalities in hearts with HCM. PMID- 7776546 TI - [Restoration filtering based on projection power spectrum for single-photon emission computed tomography]. AB - To improve the quality of single-photon emission computed tomographic (SPECT) images, a restoration filter has been developed. This filter was designed according to practical "least squares filter" theory. It is necessary to know the object power spectrum and the noise power spectrum. The power spectrum is estimated from the power spectrum of a projection, when the high-frequency power spectrum of a projection is adequately approximated as a polynomial exponential expression. A study of the restoration with the filter based on a projection power spectrum was conducted, and compared with that of the "Butterworth" filtering method (cut-off frequency of 0.15 cycles/pixel), and "Wiener" filtering (signal-to-noise power spectrum ratio was a constant). Normalized mean-squared errors (NMSE) of the phantom, two line sources located in a 99mTc filled cylinder, were used. NMSE of the "Butterworth" filter, "Wiener" filter, and filtering based on a power spectrum were 0.77, 0.83, and 0.76 respectively. Clinically, brain SPECT images utilizing this new restoration filter improved the contrast. Thus, this filter may be useful in diagnosis of SPECT images. PMID- 7776545 TI - [The role of gallium-67 citrate scintigraphy in Crohn's disease]. AB - We investigated the usefulness of gallium scintigraphy and its importance in the choice of a treatment method for Crohn's disease. The subjects for the study were 30 patients diagnosed as Crohn's disease. After intravenous injections of 67Ga citrate 111 MBq, planar and SPECT images were taken at 48 and 72 hrs. The overall positive rate was 42.1%, and among the positive cases, 78.6% required surgical treatment. On the other hand, surgical treatment was only performed in 18.8% of the negative cases, which was significantly low percentage. However, since 75% of the cases, in whom surgical treatment was performed, showed preoperative positive 67Ga results, positive cases detected by 67Ga scintigraphy were considered to be high-risk cases requiring surgical treatment. PMID- 7776548 TI - [Serial assessment of MIBG scintigraphy in a case of DCM with heart failure improved by beta-blocker therapy]. AB - We experienced a case of DCM (62-year-old man) improved by beta-blocker (Metoprolol) therapy and studied time course of MIBG scintigraphy. We measured cardiac functions by UCG and 99mTc cardiac pool imaging, and MIBG scintigraphy during 12 months of beta-blocker therapy. In planar images we measured washout rate (WR) in total myocardium and regional washout rate (rWR) in 6 segments of myocardium. Cardiac function improved after 3 months of therapy. The WR did not improve until 6 months, but improved after 9 months (Before: 35.1%, 3 months after: 34.6%, 6 months after: 33.6%, 9 months after: 27.6%, 12 months after: 25.4%). rWR in inferoapical segment first improved at 3 months (Before: 40.1%, 3 months after: 35.1%), whereas rWR in antero-apical segment improved after 6 months and that in anterior segment improved after 9 months. These results suggest that the improvement of cardiac sympathetic nerve function in DCM treated with beta-blocker was not identical in each myocardium region. PMID- 7776547 TI - [A study of rCBF measurement with autoradiography (ARG) method using N-isopropyl p-[123I]iodoamphetamine (IMP) and SPECT--comparison of rCBF values between look up table (TLU) and ARG methods, and evaluation of venous blood samplings as a substitute for arterial blood sampling]. AB - Regional cerebral blood flow (rCBF) values obtained by the TLU method with two 123I-IMP SPECT scans and one point arterial blood sampling and rCBF obtained by the ARG method with one 123I-IMP SPECT scan and fixed distribution volume (Vd) values were compared in 17 cases. A case with post ischemic hyperperfusion or luxury perfusion was not observed in our cases. The correlation coefficients between rCBF values and Vd values obtained by the TLU method were 0.49 (p < 0.001) in 184 ROI without hypoactive areas on the early image, and 0.61 (p < 0.001) in 207 ROI with hypoactive areas, respectively. A high rCBF value with a low Vd value was not observed in any region. Mean Vd value was 44.0 +/- 7.0 (mean +/- SD) in all regions. The correlation coefficients between rCBF values using the TLU method and those using the ARG method with Vd fixed at 44 and 50 were also 0.98. Error of the rCBF value was larger in the region of high rCBF, however, noticeable error of the rCBF value was not observed in the ARG method. The ARG method is more convenient for quantifying rCBF. Venous blood radioactivity at 10 min after 123I-IMP infusion was smaller than arterial blood radioactivity, and the blood activity in the distal vein was larger than that in the proximal vein. The ratio of venous blood activity to arterial blood activity was 0.92 +/- 0.04 (mean +/- SD) at the back of the hand, however, the ratio was a variant in each case. Arterial sampling was thought to be a reliable method to obtain more stable and precise rCBF. PMID- 7776549 TI - [Changes of liver function measured by 99mTc-GSA scintigraphy after hepatectomy]. AB - In 14 patients with hepatic tumors, liver volume and liver function indices were studied by 99mTc-GSA liver scintigraphy before and after hepatectomy. The liver volume measured by 99mTc-GSA SPECT was significantly decreased after surgery in all 14 patients (p < 0.001). Postsurgically, 7 patients showed an increase of greater than 10% in the LU15 value, while 3 showed a decrease of 10% in the LU15 value, while 3 showed a decrease of 10%. Two patients showed a decrease of greater than 10% in the HH15 value after surgery. The changes in LU15 after surgery were inversely correlated with those in HH15. The present findings clarified that in several cases of surgically treated hepatic tumors, 99mTc-GSA indices of liver function generally thought to indicate the size of the functioning liver cell mass were distinctly improved after surgery in comparison with those before surgery, despite the postoperative decrease in the liver volume. Furthermore, the results of a 99mTc-GSA SPECT study separately measuring the volume of the unilateral hepatic lobe and its radioactivity uptake, indicated that regeneration of the functioning liver cells often occurred in the entire liver. 99mTc-GSA scintigraphy appears to be a valuable method for evaluating changes in both the liver volume and the liver function indices after hepatectomy. PMID- 7776550 TI - [Quantitative analysis of individual renal function using 99mTc-DMSA scintigram- comparison with 131I-OIH renogram]. AB - 99mTc-2,3-di-mercapto-succinic acid (DMSA) is able to be used for the quantitative analysis of individual renal function by calculating the uptake ratio. The purpose of this study is to assess the clinical feasibility of DMSA uptake ratio as compared with 131I-ortho-iodo-hippuran (OIH) renogram pattern. Two hundred eleven cases (191 patients, 1 to 87 years old) with renal disorders and 4 normal volunteers (27.8 +/- 2.4 years old) were studied. Just prior to the DMSA study in the same day, OIH renogram was carried out. They were divided into 6 types by OIH renogram patterns. In 24 cases of normal renogram pattern and normal blood data who were defined as the normal group and 4 normal volunteers, DMSA uptake ratio showed negative correlation with increasing age (r = 0.61, p < 0.05). Patients of the severe impaired functioning and the non functioning patterns showed significantly decreased DMSA uptake ratios as compared with the normal pattern. There was also a significant difference in DMSA uptake between impaired functioning patterns. Compensative hemi-hypertrophy kidneys showed significantly higher DMSA uptake ratios than those of atrophic kidneys. The possibility of the quantitative analysis of the functional compensation was presumed. In conclusion, quantitative analysis of individual renal function using DMSA uptake ratio is considered to be useful to evaluate the renal functional reserve. PMID- 7776551 TI - [Renovascular hypertension and captopril-enhanced renal scintigraphy]. AB - Renovascular hypertension (RVH) is a secondary hypertension that is caused by the renal artery stenosis and is curable by surgical treatment. Sensitivity and specificity of CRS for RVH have been reported to be in exceed of 90%. Captopril enhanced renal scintigraphy (CRS) has become an important tool in the diagnosis of RVH. In addition, the recent reports indicate that CRS is a promising means of prognostic evaluation in re-vascularization of RVH. In this report, pathophysiological considerations, methods, diagnostic criteria, diagnostic efficacy and consideration for clinical application are reviewed. PMID- 7776552 TI - [Evaluation and management of children with neurogenic bladder]. PMID- 7776553 TI - [Usefulness of fine needle aspiration cytology in the diagnosis of prostate cancer]. AB - The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer. PMID- 7776554 TI - [Evaluation of renal graft function with radionuclide dynamic images--with special reference to the application of the modified Rutland's analytical method]. AB - In calculation of an uptake coefficient (UC), proportional to the glomerular filtration rate for renal dynamic images with 99mTc diethyl triamine pentaacetate (DTPA), by the graphic method proposed by Rutland. We developed a new method of estimating input and output functions, by applying a factor analysis method to the renal dynamic images. The purposes of this paper are to describe the results obtained through phantom experiments and its clinical application. In the phantom experiments, a hemofilter was used as a method for real kidney and the filtration rate was changed to estimate the reproducibility of UCs. the UCs were estimated by trying different input functions; abdominal aorta curve, renal artery curve and intrarenal artery curve. The UCs estimated by using the intrarenal artery curve as an input function showed the best correlation with the pre-determined filtration rate. In clinical applications 8 normal subjects, 3 patients with acute renal failure, 11 donors and 22 recipients were studied. The USs obtained were compared with clinical data of renal function. A group of subjects having with both kidneys in the normal body space were classified as Cluster 1, another group of transplant recipients were classified as Cluster 2. In Cluster 1 the UCs showed a good correlation with Ccr (r = 0.909), and effective renal plasma flow (r = 0.798), and an inverse correlation between UCs and serum creatinine values (r = 0.747). The median value of UCs in 11 donors at pretransplantation were 0.30, which increased to 0.46 at 3 weeks after transplantation. Cluster 2 has many risk factors (to be abnormal space, rejection, toxicity of Cyclosporin and immuno suppression) compared to Cluster 1, but in Cluster 2 the UCs showed a good correlation with Ccr (r = 0.955), and effective renal plasma flow (r = 0.653), and an inverse correlation between UCs and serum creatinine values (r = 0.857). Cluster 1 and Cluster 2 showed the same correlations with Ccr and UCs. But Cluster 1 is a different group from Cluster 2. The results of the study showed that the modified Rutland's analy analytical method can estimate the renal filtration rate accurately, evaluate the residual renal function in donors quantitatively and be a useful parameter for monitoring renal graft function. PMID- 7776556 TI - [Kinetic study of local relapse in prostatic cancer]. AB - The change of both prostatic volume and bone metastasis was observed from the period of castration to death in 23 cases of prostatic cancer. As for the change of prostatic volume, they were classified into two groups. One group was called "local progressive type". In this group, prostatic volume reduced exponentially after the treatment of castration, then increased exponentially after a transient period. Another group was called "metastatic progressive type". In this group, prostatic volume did not change after the treatment of castration although the degree of bone metastasis advanced severely. The regression speed after castration (tau) was faster in local progressive type than in metastatic progressive type. This tau had a close relationship to the prognosis of each case. In local progressive type, doubling time (DT) during relapsed period was calculated in 13 cases. An inverse correlation was found between tau and DT. This correlation might be able to lead the conclusion that the ratio between residual androgen sensitive cancerous tissue and residual androgen insensitive cancerous tissue related to the local progression in relapsed prostatic cancer. PMID- 7776555 TI - [A pathological comparison of primary and metastatic lesions as a prognostic indicator for renal cell carcinoma]. AB - The purpose of this study is clarify the changes in histological grade between primary and metastatic lesions in renal cell carcinoma. A tota of 100 cases of renal cell carcinoma and their metastases were compared respectively. In 31 (31%) of the cases observed, metastatic lesions were observed to have higher grade of malignancy when compared to primary lesions. In 59 (59%) of the cases, metastatic lesions had the same grade of malignancy and in 10 (10%) of the cases, metastatic lesions had a lower grade of malignancy when compared to primary lesions. The frequency of upgrading cases in young patients (i.e. less than 40 years old) occurred with less frequency when compared to elderly patients. Additionally, the frequency of upgrading cases involving female patients was lower when compared to male patients. The one year survival rates in patients, who received nephrectomy, having grade 1 to 4 lesions following metastases were 100%, 65%, 71%, and 27% respectively. From these percentages, a statistically significant difference exists in one year survival rates between patients with grade 2 and 4 metastatic lesions (p < 0.005), and grade 3 and 4 metastatic lesions (p < 0.01). Histological grade of metastatic lesions is an important prognostic indicator for determining the outcome of renal cell carcinoma following metastases. Thus it is important that the prognosis of renal cell carcinoma be based on the histological grade of metastatic lesions as well as primary lesions. PMID- 7776557 TI - [The efficacy of endopyeloureterotomy via a transpelvic extraureteral approach]. AB - To evaluate the efficacy of endopyeloureterotomy via a transpelvic extraureteral approach for the treatment of ureteropelvic junction obstruction or upper ureteric stenosis, we analysed the results of 85 patients treated with this procedure between Aug. 1988 and June 1993. Eighty-five patients underwent 87 procedures. Each patient has been followed-up more than 6 months postoperatively. Of 87 procedures, 71 were performed in patients with ureteropelvic junction obstruction and 16 were in patients with stenosis of the upper third ureter. Primary disease was 59 and secondary disease was 28. Twenty-one procedures were performed in patients with the stenotic segment over 2 cm. The operative procedure was performed by first incising with a 22 Fr. urethrotome (ACMI Co.); the dilated renal pelvic or ureteral wall posterolaterally as long as 1-1.5 cm junction from the stenotic segment toward ureteropelvic junction, then bringing the urethrotome out retroperitoneally through the incision and finally incising the stenotic segment with the cold knife under direct vision. A 12-16 Fr. PTCS tube (Sumitomo Behkuraito Co.) was left in place for 3 weeks as a stent. Mean operative time was 101 min and average length of incised segment was 3.7 cm. Complication included pneumothorax (1 case), pseudo ureter (1 case) and renal arterial anexryma (1 case). Followed-up period ranged from 6 to 64 months with the average being 26 months. Of 87 procedures, 80 (92%) achieved a disappearance or improvement of the obstructive change and 7 failed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776558 TI - [Effect of caffeine and pentoxifylline on human sperm motility after one week storage at 3 degrees C]. AB - The effect of caffeine (C) and pentoxifylline (P) on the sperm motility was examined after a 3 degrees C storage in a TEST yolk buffer for one week. Thus stored 24 semen samples from infertile patients were incubated with or without C or P at 37 degrees C. The motility was analysed for up to 240 minutes. The poststorage addition of C (1 mM) and P (1 mM) significantly increased the serum motility rate (p < 0.01). The stimulant effect of C and P was rather transient lasting no more than 2 hours. The prestorage addition of C and P in a preservant TEST yolk buffer was less effective than the poststorage administration. According to the time-related profiles of the sperm motility, 24 cases were divided into three groups. In group A (11 cases), the sperm motility rate increased from 30 to 90 minutes even without C or P. This group was responder of C and P. In group B (8 cases), the motility rate increased only in response to C and P and, in group C (5 cases), no such responses were observed. The prestorage semen qualities in terms of the sperm concentration, the motility rate, the velocity, the linearity, and the amplitude of the lateral head displacement were compared in these three groups. There was a significant difference between these 3 groups (p < 0.05) on the parameters in terms of the sperm concentration, motility rate and velocity. It was suggested that these prestorage parameters predict the sperm activity in response to C and P after a one week 3 degrees C storage. PMID- 7776559 TI - [Carcinoma of the renal pelvis and ureter following bladder carcinoma]. AB - We followed 135 primary bladder carcinoma patients for at least 3 years. Subsequent carcinomas of the upper urinary tract were found in 5 patients (3.7 per cent) an average of 67 months after an initial treatment of the bladder tumors. Two patients underwent radical cystectomy and the remaining 3 patients received transurethral resections or partial cystectomy five to seven times for bladder lesions. Primary bladder tumor was multiple in all and one of them was accompanied by carcinoma in situ in the bladder and urethra. Except for one patient who presented with gross hematuria, four patients had no symptoms referable to the upper urinary tract tumor. However two of them had high stage disease. Positive urinary cytology was observed in only one patient. All patients underwent nephroureterectomy and the four got well but one died of acute heart failure. Regular urinary cytology and IVP should be done for an extended period of time for early detection of renal pelvic and ureter cancers in patients who had multiple and recurrent bladder cancers. PMID- 7776560 TI - [Evaluation of the efficacy of recombinant human erythropoietin (rHuEPO) administration on penile erection in males undergoing hemodialysis and effect on pituitary-gonadal function]. AB - Recombinant human erythropoietin (rHuEPO) was administered to males undergoing hemodialysis, and its effects on penile erection and hypothalamus-pituitary gonadal hormone levels were studied. The subject consisted of 18 males undergoing hemodialysis ranging in age from 22 to 58 years (mean 45.3 years). Chronic glomerulonephritis was present in 16, and diabetic nephropathy in 2, as underlying disease. rHuEPO was administered intravenously at 1,500 U 3 times a week with a target to increase the Ht value to 25% or above. Penile erection was evaluated subjectively by a questionnaire based on a visual analogue scale and objectively by semi quantitative measurement of nocturnal penile tumescence (NPT) using an erectometer. Of the 18 patients, subjective improvements in penile erection were observed in 13 (72%), and objective improvements in NPT were observed in 10 (56%). The administration of rHuEPO may alleviate hyperprolactinemia but was found to have no effect on the FSH, LH, Zn, or HS-PTH level. rHuEPO was suggested to be fairly effective for the treatment of sexual disorders. PMID- 7776561 TI - [Pelvic lymph node involvement in primary bladder cancer. A clinicopathological study of radical cystectomies]. AB - Between 1984 and 1992, 131 patients with bladder cancer underwent radical cystectomy and pelvic lymph node dissection with urinary diversion. There were 110 male and 21 female patients, aged between 35 and 86 with a mean of 64 years. The follow-up period ranged from 1 month to 113 months, with a median of 34 months. The five-year survival estimated by the Kaplan-Meier method was 66.9% over all 131 patients. The five-year survival rates were 83.3% for stage pTis patients, 66.7% for stage pTa, 97.0% for pT1, 70.7% for pT2, 47.9% for pT3a, 26.2% for pT3b, and four-year survival was 25% for pT4 disease. Under the grading system, the five-year survival was 80.0% for cases of grade 2 disease and 63.6% for grade 3. There were two grade 1 patients who died of other diseases 15 and 16 months after surgery. Of all 131 patients, 22 (16.8%) had lymph node involvement. The five-year survival was 34.5% for patients with positive lymph nodes in comparison with 73.8% for those without lymph node involvement. The frequency of lymph node involvement was 26.1% in the non TCC group and 14.8% in the TCC group including 23.7% of the grade 3 and 4.3% of the grade 2 cases. Pathologically, the patients with higher stages had a higher frequency of lymph node involvement, and there was a significant difference in the frequency between pT3a (14.3%) and pT3b (47.8%) disease. The five-year survival of patients with positive lymph nodes was 40.0% for pN1, 32.1% for pN2 disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776562 TI - [The role of the vertebral veins in the dissemination of prostate carcinoma]. AB - A total of 75 prostate cancer and 67 lung cancer patients with positive bone scintigrams were studied. The patterns of spread of tumors to various bones were different between the 2 groups. The differences in the distribution of bony metastases between the prostate and lung are explained by the role of Batson's vertebral venous plexus. PMID- 7776563 TI - [Evaluation of advanced bladder tumor]. AB - Ninety-two cases of advanced bladder tumor treated at the University of Tokyo and branch hospital from January 1977 to December 1992 were analyzed. The advanced bladder tumor was defined as that of higher than pT2 (according to the General Rule for Clinical and Pathological Studies on Bladder Cancer) or that with distant metastases. The following variants were evaluated, the therapeutic methods, the histological type, grade, stage, type of infiltration. The evidence of lymphatic infiltration, vessel infiltration, and lymph node metastases were also reviewed. The survival rate was calculated using Kaplan-Meier's method. In the cases with lymph node metastases, the survival rate was significantly lower than in the cases without metastases (p < 0.01), while no other factors affected the survival rate. PMID- 7776564 TI - [A study on intratesticular aromatase activity in male infertility]. AB - We report here the influence of intratesticular aromatase activity and intratesticular estrogen concentration on spermatogenesis. In the present study, we measured the levels of aromatase activity and the concentrations of intratesticular testosterone (T) and estradiol (E2) in 21 testicular tissues from biopsy of 20 idiopathic male infertility patients, 5 testicular tissues from castration of 4 prostatic cancer patients and a testicular tissue from an autopsy. Serum T, Free T, E2, LH and FSH were also measured if possible. Aromatase activity in the testis were assayed by measuring the amount of 3H2O formed during the conversion of [1 beta-3H] androstenedione to estrogen. Histological evaluation of the testes were performed using the Johnsen's score count (JSC) method. The rate of aromatase activity was linear in regard to time and amount of tissue. The production of 3H2O was inhibited by 4 hydroxyandrostenedione. The apparent Km (Michaelis constant) of the reaction was 23.2 nM. The rate of aromatase activity increased linearly as JSC level decreased (r = 0.67). Also, it significantly correlated with intratesticular T (r = 0.69), E2 (r = 0.88) and T/E2 ratio (r = -0.85), whereas it was not correlated with serum T, free T, E2, T/E2 ratio and free T/E2 ratio. Therefore, our results suggest the possibility that the increase in the rate of aromatase activity and the concentration of E2 may influence spermatogenesis. PMID- 7776565 TI - [Uretero-aortic fistula: a case report of a serious complication of indwelling ureteral catheter]. AB - We present a case of a uretero-aortic fistula assumed to be caused by an indwelling ureteral catheter. A 65-year-old male who underwent cystectomy and ureterocutaneostomy with bilateral ureteral stents had been well until gross hematuria from the left catheter developed. In spite of a through radiological examination of the left kidney, no abnormal findings were noted. However, massive hemorrhage was encountered on catheter exchange, prompting us to suspect a formation of a uretero-arterial fistula. CT scan was performed again, demonstrating severe adhesion between the left ureter and the aorta at the crossing point. At exploration, a fistula of about 7 mm between the left ureter and anterior surface of the aorta was recognized. Left nephro-ureterectomy and closure of the aortic fistula with a rectus muscle fascia wrapping was successfully performed. His postoperative course was uneventful. Because the continued increase in the utilization of ureteral catheters could cause frequent occurrence of this condition, urologists should be aware of a uretero-arterial fistula as possible serious complication of indwelling ureteral catheters. PMID- 7776566 TI - [Extracorporeal shock wave lithotripsy for urinary calculi in an ileal reservoir following reconstruction of the urinary bladder]. AB - A new method for reconstruction of the urinary bladder was introduced by Taguchi in 1977. It consisted of two components; making of pseudo-urethra and the reconstruction of urinary reservoir in the pelvis. The latter was made of the ileum and the peritoneum with temporary use of Japanese paper. This operative method was applied to a 28-year-old female patient when she had cystectomy and bilateral ureterostomy. Thereafter she had has no trouble for 13 years. However, her recent rentogenogram showed urinary tract calculi in the reservoir. Endoscopic treatment was not indicated because of the deformed reservoir and the inflexible pseudourethra. Thus, extracorporeal shock wave lithotripsy (ESWL) was applied to the case with successful results. We herrin reported the case and discussed the usefulness of ESWL for urinali calculi in the ileal reservoir. PMID- 7776568 TI - President's message: the best of times ... the worst of times. PMID- 7776567 TI - [Deoxycorticosterone-producing adrenocortical carcinoma--a case report]. AB - A 39-year-old male presented with gross hematuria and left lower abdominal discomfort. Excretory urography showed a left ureteral stone and hydronephrosis. CT scans and magnetic resonance imaging showed a solid mass at the upper pole of the left kidney. Angiography revealed a hypervascular lesion at this area. The laboratory data showed a slightly decreased serum potassium level. In the endocrinological study, the serum deoxycorticosterone (DOC) level was markedly elevated. There was, however, no evidence of hypertension. The operation was performed on November 13, 1992. The tumor was almost separated from the left kidney, but an aberrant artery which divided from the renal artery and penetrated the renal parenchyma was found. Therefore, we had to carry out en bloc removal of the tumor together with the left kidney and the ureter which contained the ureteral stone. Pathological diagnosis was adrenocortical carcinoma. After the operation, hypokalemia and the serum concentration of DOC returned to normal range. Therefore, the tumor was diagnosed as DOC producing adrenocortical carcinoma. The patient was discharged 30 days after the operation with uneventful postoperative course. He received 2.5 g of op'-DDD a day. There was no evidence of distant metastasis or local recurrence 12 months after the operation. Nineteen cases of DOC producing adrenocortical tumor have been reported in the world literature. A case and a review of the literature are herein reported. PMID- 7776569 TI - Patterns of injury in pediatric patients in one Florida community and implications for prevention programs. AB - OBJECTIVES: To meet community needs, injury prevention programs for children should be based on an understanding of the patterns of different mechanisms of injury. This study was conducted by the staff of a level II pediatric trauma center to describe the patterns of injury in pediatric patients with traumatic injuries. METHODS: We conducted a retrospective review of medical records of all 184 pediatric "trauma alert" patients seen during a 1-year period. The trauma alert status is assigned to children with serious injuries or when the mechanism of injury is severe. Data analysis used descriptive statistics. RESULTS: Pedestrian-versus-automobile injuries were the most common and most severe injuries, followed in frequency by falls, motor vehicle occupant, and bicycle versus-automobile injuries. Younger children tended to have injuries as a result of falls; school-age children were involved more often in pedestrian and bicycle injuries, and adolescents had more motor vehicle occupant injuries. Failure to use safety devices, such as helmets and seat belts, was a common finding. DISCUSSION: Patterns of injury were similar to those described in national studies. An extensive helmet campaign directed at child bicyclists was developed as a result of the priorities generated from the study. Other community programs included bicycle rodeos and a mix-off of nonalcoholic beverages. PMID- 7776571 TI - Planning and moving to a new emergency department: one hospital's experience. PMID- 7776570 TI - Emergency department patient liaison volunteers: a cost containment and visitor satisfaction strategy. AB - We have saved a minimum of $17,064 in personnel salaries of a patient representative (based on minimum wage and no paid benefits) during the past year. Although our liaison program was initially started as a cost-saving measure, the benefits of the program cannot be measured in monetary terms. Although this venture was our first attempt with a program of this nature, and we are still developing the program, we believe the development of the ED liaison volunteer program has been a major accomplishment for the emergency department and has also increased community support. Many of the liaisons were totally unaware of the activities in an emergency department. They now have a greater appreciation for the process of emergency care, and can relate that understanding to patients and families. PMID- 7776572 TI - Adverse effects of epinephrine when given to patients taking propranolol (inderal). PMID- 7776573 TI - Case studies in work redesign: cost considerations in a work redesign project. AB - Regardless of the limitations and comprehensiveness of plans for redesign, at least one common consideration prevails. Decisions to redesign should be well planned with specific attention to the details of the costs involved. As the unique needs of the institution are incorporated into the plan, a thorough cost benefit analysis should be used to determine final decisions. Without specific attention to a number of factors, including those noted above, the restructuring project may fall short of the intended goals of reducing costs and may actually increase costs. PMID- 7776574 TI - The road from Goma to Kigali: caring for refugees in Rwanda. PMID- 7776575 TI - Infectious disease screening and isolation for pediatric patients in an emergency department. PMID- 7776576 TI - A look at our new emergency department: Memorial Hospital, Colorado Springs, Colorado. PMID- 7776577 TI - "It's not a testing station!". PMID- 7776578 TI - Assault support team. PMID- 7776579 TI - The daughter that was nurse. PMID- 7776580 TI - Intravenous magnesium sulfate for acute asthma. PMID- 7776581 TI - The evolving change in paradigm from quality assurance to continuous quality improvement in prehospital care. PMID- 7776582 TI - Violence against nurses: is it a felony or not? PMID- 7776583 TI - A "liberation management" (shared-governance) model for a flight program. PMID- 7776584 TI - ED chest pain triage, TPA, and streptokinase checklists. PMID- 7776585 TI - Self-scheduling in the emergency department. AB - The primary steps to accomplish successful self-scheduling programs are as follows: 1. An appropriate amount of time must be committed for a trial period; a minimum of 6 months is recommended. In the initial phases of the program, it is important that the manager refrain from intervening in conflict resolution or allowing the staff members to abdicate decision making to management when problems arise. Changes in staff attitudes to assume responsibility for unit coverage emerge, in part, as a result of observing the consequences when it is not done. 2. At least 1 year, and often almost 2 years, are required to achieve smooth-flowing systems. 3. Time is needed for the staff members to become proficient in negotiation. The key to mutual cooperation is that everyone eventually experiences a need for a change in his or her particular schedule. The staff may need assistance in learning how to perceive possible changes or how to approach others. 4. Problems are usually resolved by staff-suggested rule additions or modifications. Rules can be used to help enforce consideration and fairness, but a noncompliant person may need individual attention. PMID- 7776586 TI - On-line charging = increased revenue. AB - Although the new ED charge system is not perfect, it has resulted in improved charging for services delivered; this increase in correct charges has more than offset the resources to develop the entire tracking system project within 1 year. This is one example in which computerization paid for itself, which should help ED managers justify computerization of their departments. It is hoped that more effective charge systems will occur as a component of the computerized patient record in which the patient charge is calculated on the basis of preset formulas for the amount of resources utilized, thus eliminating subjectivity in charging. With the capture of all services rendered, evaluation of practice patterns and outcomes would allow the ED staff to identify effective treatment regimens. Hopefully, unnecessary tests or treatments can be eliminated to promote a decrease in resource utilization and costs without compromising quality patient care. PMID- 7776587 TI - Triage protocols. PMID- 7776589 TI - Trauma resource nurse orientation program. PMID- 7776588 TI - Human immunodeficiency virus and acquired immunodeficiency syndrome: updating the MMWR file. PMID- 7776590 TI - Mobitz I versus Mobitz II: learning through storytelling. PMID- 7776591 TI - Autoerotic asphyxia in adolescents. AB - The death of a child or young adult is always tragic, regardless of the cause. Cases of autoerotic asphyxia are often labeled as suicide, or are underreported because of embarrassment of relatives or misidentification of the initial clinical manifestations. It may be that autoerotic asphyxial death is far more common than realized. Many emergency nurses and physicians lack adequate knowledge about this phenomenon to make an accurate diagnosis. Family members are often reluctant or unwilling to provide enough data surrounding the circumstances in which the patient was found, and the cause of death is mislabeled as suicide. Autoerotic asphyxia is frequently labeled as a sexual aberrancy and an act that society would rather not acknowledge. But there are a number of implications for emergency nurses, such as prevention and sensitive support of family in the emergency department, that demand our attention. PMID- 7776592 TI - Automobile air bag-mediated injury: a case presentation. AB - Because of the growing number of automobiles equipped with air bags, it is virtually certain that patients will seek treatment in the emergency department for air bag-mediated injury. The emergency nurse must be aware of air bag mediated injury patterns and prepared for triage and management of any of the potential concurrent injuries caused by air-bag deployment. PMID- 7776593 TI - A 42-year-old woman with unexplained swelling of the hand and forearm. PMID- 7776594 TI - A tribute to Barb Fassbinder. PMID- 7776595 TI - Jeremy. PMID- 7776596 TI - Acute iron ingestion in a 2-year-old child. PMID- 7776597 TI - "Please keep his hands warm". PMID- 7776598 TI - "Triaging out" children with minor illnesses from an emergency department by a triage nurse: where do they go? AB - OBJECTIVE: To determine whether parents of children with minor illnesses actually seek care after they receive advice and are referred from an emergency department by an ED triage nurse. DESIGN: Descriptive study of 100 parents with children who were given advice and referred from an urban, pediatric tertiary care center by an ED triage nurse. METHODS: A 10-item telephone survey was designed to determine whether parents took their children to the primary health care provider to whom they were likely to be referred. Parental perceptions of the severity of the child's medical problem, of the nurse's understanding of the problem, and of the satisfaction with the referral process were analyzed with Fisher's exact test. RESULTS: Most (79%) of the subjects did not seek care with a primary health care provider per referral. However, 81% of parents believed the triage nurse understood the child's problem (rated 4 or 5 on a 5-point Likert scale in which 5 meant "completely understood" the child's problem) and 79% were satisfied with being referred from the emergency department (rated 4 or 5 on a 5-point Likert scale in which 5 meant "most satisfied" with being "triaged out"). CONCLUSION: Parental perceptions of the ED triage nurse's understanding of the child's complaint has a significant positive relationship on the parent's satisfaction with the advice and referral directives given by the nurse for the health care needs of the child. No children in this study experienced a worsening in their condition. Hence the ED triage nurse can be a valuable resource in educating and fostering primary health care practices within the community. PMID- 7776599 TI - Cocaine-induced myocardial infarction: treatment with thrombolytic therapy. AB - Patients with cocaine-induced AMI may be added to the expanding list of eligible candidates for thrombolytic therapy. ED nurses are in key positions to identify patients for thrombolysis, evaluate patients' responses, and minimize complications. With the rising use of cocaine, increased consideration should be given to any relatively young patient with unexplained cardiovascular symptoms and history of cocaine use. PMID- 7776600 TI - Markers of reperfusion after thrombolytic therapy for acute myocardial infarction. PMID- 7776602 TI - Syncope: categories and considerations for practice. AB - Cardiogenic and orthostatic syncope can be diagnosed in the majority of cases in the ED setting. Neurogenic causes of syncope may require more extensive testing and a longer in-hospital stay to determine the underlying cause. However, with the advent of more definitive laboratory tests such as CK determination, neurologic syncope may be more easily diagnosed in the emergency department. It is hoped that the morbidity and mortality rate related to syncope (falls, motor vehicle accidents) will decline with patient education, early diagnosis, and treatment. Cognizance of the various types and categories of syncope can assist the emergency nurse in triage, as well as enhance the differential diagnosis and treatment of the patient with syncope. PMID- 7776601 TI - Ketamine: the dissociative anesthetic and the development of a policy for its safe administration in the pediatric emergency department. PMID- 7776603 TI - Economical citywide tabletop disaster preparedness drill. PMID- 7776604 TI - Torsades de pointes: success equals recognition. PMID- 7776605 TI - The surprise gift. PMID- 7776606 TI - The evolution of air medical transport. PMID- 7776608 TI - Telephone consultation for a "managed care" population. PMID- 7776607 TI - Emergency care flow sheet. PMID- 7776610 TI - Nurses and the Internet. PMID- 7776609 TI - Providing educational information. PMID- 7776611 TI - Phone consultations with the ED physician: is there nursing liability? PMID- 7776612 TI - ACLS rapid rate conversion drugs. PMID- 7776613 TI - Pediatric quality improvement in the emergency department. PMID- 7776614 TI - ENA's new course in advanced trauma nursing: a conceptual approach. PMID- 7776615 TI - A 74-year-old woman with dizziness, lower extremity weakness, and slurred speech. PMID- 7776616 TI - The making of ENA's anniversary quilt. PMID- 7776618 TI - A look at our new emergency department: Waynesboro Hospital, Waynesboro, Pennsylvania. PMID- 7776617 TI - Emergency nurse encounters man with seizure at 20,000 feet. PMID- 7776619 TI - Pay and benefits of Canadian emergency nurses. PMID- 7776620 TI - President's message: archiving our organization. PMID- 7776621 TI - A research report card. PMID- 7776622 TI - Reuse of eye medication in the emergency department. PMID- 7776623 TI - Dopamine not effective for treatment of hypotension in chlorpromazine overdose: first case report. AB - Dopamine is a popular and effective vasopressor agent. However, in the event of overdose with a potent alpha 1-receptor blocker, dopamine may not be effective in treatment of hypotension. A vasopressor that stimulates only alpha-receptors, such as norepinephrine or phenylephrine, may be more appropriate. In our case, dopamine was clearly ineffective, whereas norepinephrine worked well. Our case also demonstrates the importance of carefully monitoring the effectiveness of any vasopressor therapy. PMID- 7776625 TI - Human ehrlichiosis: a case report from the South Carolina lowcountry. PMID- 7776624 TI - The MUSC lung transplantation program: the first year's experience. PMID- 7776626 TI - Selective spinal injections. PMID- 7776627 TI - Applications of small wire external fixation. PMID- 7776628 TI - Ehrlichiosis: more tick-borne terrorism? PMID- 7776629 TI - What is professionalism and can it be measured? PMID- 7776630 TI - 15 characteristics of personal maturity. PMID- 7776631 TI - The Nebraska "Network of Drug-Free Youth" program. AB - This paper describes Nebraska's six-year experience with a successful prevention program to form and maintain local drug-free youth groups. More than 4,500 youth were involved at the time of a six-year evaluation survey. Nearly 91% of group members who responded reported being alcohol-free in the previous 30 days and almost all (97%) reported being tobacco-free. Thirty-eight percent of members met one or more of the federal criteria for "high-risk" youth. Sixty-eight percent of responding high-risk youth who previously used alcohol credited group membership with helping them quit or reduce use. The program appears to assist in delaying onset of alcohol, tobacco, and other drug use for youth in the program, and to assist in decreasing or eliminating use of alcohol and tobacco by adolescents who used before participating. PMID- 7776633 TI - The Delaware School Health Advisory Committee. AB - For nearly 40 years, the Delaware School Health Advisory Committee (SHAC) has been improving school health education and school health services in the state. The SHAC has recommended policies to the Delaware Board of Education and the state legislature, conducted conferences and workshops, and published brochures, studies, resource guides, curricula, and pamphlets. The key to SHAC success has been its diverse membership and the cooperation it engendered in the state. PMID- 7776632 TI - A comprehensive approach to school health program needs assessments. AB - An assessment of health promotion needs represents a fundamental step for developing comprehensive school health programs. This project developed and tested an approach for school districts to use when conducting a district-wide needs assessment of school health programs. The approach assumes a needs assessment should be multidimensional and comprehensive. Seven priority health related behaviors were included as well as eight components of a school health program identified by Kolbe. This paper describes each aspect of the needs assessment, discusses the importance of perspectives provided by each component, and provides recommendations for districts interested in conducting an assessment. PMID- 7776635 TI - A letter to my principal: why is it always health education? PMID- 7776634 TI - School-level application of a social bonding model to adolescent risk-taking behavior. AB - Adolescent bonding--attachment to, commitment to, and involvement in conventional social activities-decreases the likelihood of engaging in some risk-taking behaviors. The extent to which bonding opportunities in the school environment affect individual's bonding and risk-taking behaviors is less explored. This study tested a model that includes individual and environmental indicators of bonding to predict cigarette smoking, drinking, drug use, and sexual activity among ninth grade students. Survey data representing students in 20 schools in seven western states are reported. Twelfth grade students' bonding and other demographic variables aggregated by school served as environmental indicators of bonding opportunities to predict ninth grade students' bonding and risk-taking behavior. Path analyses indicate the school environment has a direct influence on ninth grade students' bonding and, in turn, on the likelihood they will engage in risky behavior. Implications of these findings for future research directions and intervention design are discussed. PMID- 7776636 TI - Age preferences for same- and opposite-sex partners. AB - Preferences for age of partners of heterosexual and homosexual men and women were investigated. Personal advertisements were collected from newspapers in the United States and analyzed for the difference between the age of the advertiser and the age of the preferred partner. Heterosexual men tended to seek women younger than themselves, whereas women sought partners near their own age or older. The preferences of homosexual men and women were similar to those of heterosexuals, although more homosexuals stated a preference for a partner younger than themselves. PMID- 7776637 TI - Self-perception changes among sports camp participants. AB - The relationship between sports camp participation and changes in self-perception was assessed. The participants were 42 boys and 32 girls participating in a 5 week summer sports camp for economically disadvantaged children in the United States. Self-concept was measured at the beginning and end of the camp with Harter's (1985) Self-Perception Profile (SPP) for Children. At the beginning of the camp the girls scored higher than the boys on overall SPP scores and three of six subscales. After 5 weeks, the girls' scores were higher on only one subscale and on adult group leaders' ratings. The decline in the girls' scores was attributed to the stress of competition or to initial overly positive self perceptions. PMID- 7776638 TI - Gender differences in job satisfaction. AB - The competing hypotheses of socialization, structural, and social role theories were used to investigate the possible existence of gender differences in job satisfaction. The hypotheses were tested in a sample of over 13,000 U.S. employees from approximately 130 organizations and divisions across a variety of industries. The organizations were clients of a North American-based management consulting company. T tests and effect sizes were calculated to test for the possible existence of group differences in job satisfaction between women and men in both clerical and managerial positions. The results indicate support for structural theory, some support for social role theory, and a lack of support for socialization theory. An important finding is that U.S. women and men in management apparently did not differ from one another in their sources of satisfaction at work. PMID- 7776639 TI - The effect of physical attractiveness comparison on choice of partners. AB - The roles of several presumed factors in the choice of partners during a first group encounter were examined, when the only available information was a ranking of group members' physical attractiveness. After they had received bogus feedback about their own attractiveness rank in a newly formed group, 99 Japanese students were asked to choose a partner for a task. The results indicated that feedback about one's own attractiveness was the primary factor that determined choice of others and that susceptibility to this type of feedback was characterized by a notable gender difference. These findings suggest that when the only information available about others concerns their physical appearance, the choice of partner or competitor, even for appearance-irrelevant tasks, is partially dependent on others' rankings of one's own physical attractiveness. PMID- 7776640 TI - Perception of the combined effect of smoking and alcohol on health. AB - Because smoking is significantly associated with drinking, the consumption of alcohol can be associated with indirect consumption of tobacco (passive smoking), and alcohol and tobacco can have synergetic effects, the ways people perceive their combined effects were investigated. Information integration theory was applied, and the results showed that rather than representing the combined effects of tobacco consumption and alcohol consumption in a synergetic or summative way, the sample of 40 French adults apparently considered that indulging in only one of these two behaviors results almost unilaterally in maximal alteration of health. The two effects were seen to combine disjunctively, a way of perceiving the combined effects of the two substances that runs counter to current medical data on the subject. PMID- 7776641 TI - Coping and depressive symptoms among Iranian students. AB - Five hundred sixty-eight junior and senior high school students in Tehran, Iran, completed measures of depressive symptoms and coping styles with regard to a difficult academic event. On average, the Iranian students reported more depressive symptoms than the U.S. adolescents did. Consistent with the results of studies with U.S. samples, the students who had an active coping style reported fewer depressive symptoms than the students who had a passive coping style did. These findings suggest that the Western construct of personal control functioned somewhat similarly in this non-Western sample. PMID- 7776642 TI - Stoicism: its relation to gender, attitudes toward poverty, and reactions to emotive material. AB - A scale was developed to test the hypotheses that stoicism would be more prevalent in British men (n = 30) than in British women (n = 32) and that stoicism would be related to negative attitudes toward the poor. It was also hypothesized that stoics would exhibit a weaker emotional reaction to stories that had emotive content. All three hypotheses were supported. There was evidence that the Stoicism Scale had internal consistency and some external validity. PMID- 7776643 TI - Life events, social support, and depression among Taiwanese female homemakers. AB - Eighty-five female homemakers in a Taiwanese city were surveyed. Multiple regression analysis indicated that age, life events, and social support were related to depression symptomatology. Younger homemakers reported more depressive symptoms than their older counterparts did. Life events were related to depression, and social support acted as a buffer against depression. PMID- 7776644 TI - The relationship between team friendships and burnout among residential counselors. AB - The relationship between team friendships and burnout was investigated. The participants were counselors from 16 work teams in a short-term residential facility for emotionally disturbed children and adolescents that was located in the United States. The burnout dimensions were lack of personal accomplishment, emotional exhaustion, and depersonalization (Maslach & Jackson, 1986). Reciprocal nominations between team members were used as a measure of team friendships. Friendship between members of the same team was positively related to personal accomplishment and inversely related to emotional exhaustion. The frequency of three aspects of team friendships was also examined: personal discussions, work discussions, and having fun. Having fun with a team friend was positively related to personal accomplishment, and having work discussions with a team friend was inversely related to depersonalization. The women reported more frequent contact with team friends than the men did. PMID- 7776645 TI - Predicting retirement anxiety: the roles of parental socialization and personal planning. AB - It was proposed that anxiety about retirement begins long before retirement, and that perceptions on one's parents' socialization into retirement and one's own planning for retirement are associated with retirement anxiety. Data from 213 Canadian respondents (mean age = 44 years) were analyzed. Path analysis indicated that both parental socialization and own planfulness affect retirement anxiety. PMID- 7776646 TI - Gender role identity and perceptions of Ismaili Muslim men and women. AB - Gender roles in the Ismaili Muslim community were examined. Eighty-one Shia Imami Nizari Ismaili Muslims living in Ontario, Canada, provided demographic data and completed the Bem Sex-Role Inventory (BSRI; Bem, 1981) and the Attitudes Toward Women Scale (AWS; Spence, Helmreich, & Stapp, 1973). The results indicated that, although the Muslim women had more liberal views about gender roles than the Muslim men did, both the men and the women reported views that were liberal and comparable to those that have been reported by other Canadian samples. PMID- 7776647 TI - The effect of self-serving attribution on attraction in additive- and conjunctive task groups. AB - The prediction that the effect of self-serving attribution on personal attraction will vary according to task type was tested. Twenty-four groups of Turkish students, each consisting of 1 participant and 3 confederates, received success feedback after having performed either an additive or a conjunctive task. Two of the confederates made either self-serving or group-serving attributions, whereas the 3rd confederate attributed success to the collective efforts of all group members. Following these attributions, the participants filled out a form to indicate the degree to which they preferred each member as a friend and a work mate. Self-serving attributors in the conjunctive-task condition were less preferred as friends than the self-serving attributors in the additive-task condition. Also, the additive-task participants' ratings for other group members were systematically higher than those of the conjunctive-task participants. Thus, there was a main effect of task type for both friends and workmates. PMID- 7776648 TI - Perception of crowding among children and adolescents. AB - The effects of spatial orientation (closed vs. open) and furniture arrangement (side vs. central) on Indian children's (6 to 8 years) and adolescents' (16 to 18 years) perceptions of crowding were studied, using Desor's (1972) Crowding Perception Test. The results indicated that spatial orientation and furniture arrangement had different effects on children's and adolescents' perceptions of crowding. The children perceived less crowding than the adolescents did, and central furniture arrangement was perceived as more crowded than side furniture arrangement was. PMID- 7776649 TI - Flow cytometric analysis of the DNA content in primary and metastatic lesions of colorectal cancer. AB - We investigated and compared the DNA content between primary and metastatic lesions from 30 colorectal cancer cases. The findings were only diploid in 2 cases (6.7%) and only aneuploid in 18 cases (60.0%). On the whole, the DNA ploidy agreed in 20 cases (66.7%) between both lesions. In the 18 cases with only aneuploid tumors in both lesions, the DNA index tended to be larger in the metastatic lesions than in the primary lesions. In contrast, a variation in the DNA ploidy was observed in 10 cases (33.3%). These findings show that DNA ploidy tends to remain stable during metastasis in many cases of colorectal cancer, although the DNA index did tend to be larger in metastatic lesions than in primary lesions. The existence of intertumoral heterogeneity in the DNA ploidy also shows that specimens should be investigated from both lesions in order to obtain more accurate information on the tumor and its biological behavior. PMID- 7776650 TI - Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta. AB - In our previous study on liposome-mediated transfection of the human interferon beta (HuIFN-beta) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-beta was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-beta gene inserted into a vector (pSV2IFN-beta) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-beta or other additives were simultaneously injected into the brains of rats. HuIFN-beta was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prolonged in rats treated with liposomes containing pSV2IFN-beta. However, the survival time of the treated rats was not significantly increased. PMID- 7776651 TI - Pulmonary metastasectomy for soft tissue sarcomas: is it justified? AB - The role of pulmonary metastasectomy for metastatic soft tissue sarcomas is examined by reviewing the recent (1978-1994) English language literature. There are no prospective studies that contain an appropriate control group, and only one retrospective study contains a matched control group. In those few studies that provide greater than 5-year survival data, the survival curve still has a steep slope and few patients are alive at 7 years. In most studies only one or two patients are at risk at 5 years or more. Projected survival is therefore statistically questionable. It is currently impossible to know what is the impact of the surgical procedure over and above the natural history (biology) of the tumor. A randomized, prospective study, as suggested a decade ago, is still needed. While there may be some merit to pulmonary metastasectomy in highly selected patients, aggressive pulmonary metastasectomy does not seem justified by the available data. PMID- 7776654 TI - Lectin histochemical study of cholangiocarcinoma arising from stone-bearing intrahepatic bile duct. AB - With the purpose of studying changes in the expression of glycoconjugate structures in cholangiocarcinoma and the nonneoplastic epithelium of stone bearing intrahepatic bile ducts, a panel of 12 biotinylated lectins were used on formalin-fixed, paraffin-embedded tissue sections from 13 patients who had undergone surgical resection of cholangiocarcinoma and on nonneoplastic stone bearing intrahepatic bile ducts from 10 patients. Of the 13 patients with cholangiocarcinoma 10 had hepatolithiasis and 3 did not. Among the 12 lectins, only wheat germ agglutinin (WGA) stained the cholangiocarcinoma and nonneoplastic epithelium of the stone-bearing intrahepatic bile duct. All nonneoplastic epithelia of stone-bearing intrahepatic bile ducts were stained heavily and homogeneously by WGA, the GlcNAC-specific lectin. The high columnar epithelium of both intramural and extramural glands was stained in the supranuclear region, while the low columnar epithelium of serous acini was stained in the whole cytoplasm. cytoplasm. In the well-differentiated cholangiocarcinoma, the WGA weakly stained the neoplastic cells in the supranuclear region, while it stained the luminal cytoplasmic membrane heavily. In the poorly-differentiated cholangiocarcinoma, about 50% of cancer cells were stained with WGA. The carcinoma was moderately stained in the cytoplasm. Less reactivity and a lower percentage of cells stained with lectin were found in cholangiocarcinomas when compared to nonneoplastic epithelia. This led us to conclude that there is a dramatic decrease in lectin-binding carbohydrate structures associated with cholangiocarcinoma progression. PMID- 7776653 TI - Endoscopic injection sclerotherapy for esophageal varices associated with concomitant portal venous thrombus of hepatocellular carcinoma. AB - Between 1983 and 1994, we treated 51 patients with esophageal varices and portal trunk and main branch invasion of hepatocellular carcinoma, using endoscopic injection sclerotherapy. Variceal bleeding was controlled in 28 of 29 patients (96.6%), esophageal varices were completely eradicated in 28 (54.9%), and only 2 of 28 (7.1%) bled from small, dilated, venous vessels after eradication. The cumulative nonbleeding rate at 3 years was 87.5%. Death caused by hepatocellular carcinoma accounted for 89.4% of the patients, whereas the rate of bleeding from esophageal varices was 4.3%. Variables significantly associated with the duration of survival were Okuda's clinical stage, alpha-fetoprotein, eradication of esophageal varices by sclerotherapy, and treatment of hepatocellular carcinoma, as determined in a univariate analysis. Multivariate analysis showed that eradication of esophageal varices by sclerotherapy, Okuda's clinical stage, and age were independent factors which significantly influenced survival time. We propose that complete eradication of esophageal varices and close follow-up using endoscopy may lead to a reduction in bleeding from esophageal varices, and hence may reduce mortality rates related to this bleeding. PMID- 7776652 TI - Establishment and characterization of human gastric and colonic xenograft lines resistant to CPT-11 (a new derivative of camptothecin). AB - CPT-11-resistant human gastric and colonic xenograft lines were established by direct intratumoral injection of CPT-11 into subcutaneous SC-1-NU and CC-2-NU tumors in nude mice once a week for 10 months. The resistance of these xenograft lines to CPT-11 was confirmed by growth inhibition rate, to be 36.3% and 45.4%, respectively, compared to each parent cell line. DNA topoisomerase I activity of the nuclear extracts of SC-1-NU/CPT-11 and CC-2-NU/CPT-11, as assayed by relaxation of supercoiled DNA Col-E1, was significantly less than those of the parent lines. The cellular levels of topoisomerase I in those resistant lines measured by Western blot analysis were 0.57- and 0.79-fold lower than those of the parental lines, respectively. However, the activity of DNA topoisomerase II of those resistant cell lines assayed by decatenation of kinetoplast DNA was higher than that of the parental lines and the cellular levels of topoisomerase II in the resistant lines measured by Western blot analysis were 10.8- and 8.1 fold higher than those of the parent lines. Intracellular accumulation of CPT-11 in CPT-11-resistant tumors was not changed as compared to that of the parental lines, but hydrolysis of CPT-11 to more active SN-38 was reduced in the resistant tumors. PMID- 7776655 TI - Concomitant sclerosing mesenteritis and inflammatory pseudotumor simulating gastric lymphoma or linitis plastica. AB - Both inflammatory pseudotumors and sclerosing (retractile) mesenteritis are uncommon conditions of unknown origin. A number of authors have reported patients presenting with complaints that were attributed to one or the other of these entities. In our review of the literature, we were unable to find a single case report of mixed abdominal findings that could be explained by the presence of both conditions. We report a case of the patient presenting with abdominal mass that was identified as having features of both sclerosing mesenteritis and inflammatory pseudotumor on pathologic diagnosis. PMID- 7776656 TI - Spindle cell tumor of the portal vein. AB - The authors describe the first reported case of spindle cell tumor of the portal vein (SCTPV) surgically excised in a 28-year-old woman. The tumor had caused portal vein obstruction with extensive collaterals. A side-to-side mesocaval shunt was created to reduce portal hypertension. Six months later the SCTPV could be excised. Radiation therapy (4,500 cGY) was given 2 months later. Although the tumor recurred in the liver 4 years later, the patient is alive and free of symptoms 6 years after the initial diagnosis. PMID- 7776657 TI - Synchronous, bilateral mastectomy. AB - Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination. PMID- 7776658 TI - Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro. AB - The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60 95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines. PMID- 7776659 TI - Renal cell carcinoma extending to the renal vein and inferior vena cava: results of surgical treatment and prognostic factors. AB - Forty-seven patients with renal cell carcinoma with tumor thrombus extension to the renal vein or inferior vena cava (IVC) were treated surgically over a 10-year period. There were 41 males and 6 females with a mean age of 45.7 years. Thirty three patients had right-sided and 14 had left-sided tumors. Patients with renal vein or infrahepatic IVC thrombus were treated with radical nephrectomy with tumor thrombus excision after achieving conventional vascular control over the IVC and the opposite renal vein. Four patients with retrohepatic IVC thrombus were treated with venacavotomy and thrombectomy after achieving vascular control above the thrombus but below the hepatic veins while two other patients with retrohepatic and one with suprahepatic thrombus required a bifemoroatrial partial venous bypass prior to tumor thrombectomy. There was one postoperative death due to pulmonary embolism. The actuarial 5-year survival for all patients with venous extension was 50% and the median survival was 4.35 years. Perinephric spread and lymph node metastases were significant prognostic factors affecting survival. This suggests that it is the locoregional spread of renal cell carcinoma rather than the level of the thrombus which governs the prognosis of patients with tumor thrombus extension to the renal vein or IVC. PMID- 7776660 TI - The evaluation of hepatoprotective effects of Taiwan folk medicine 'teng-khia-u'. AB - 'Teng-khia-u' is a folk medicine of Taiwan, derived from the entire plants of Elephantopus scaber L., E. mollis H.B.K. and Pseudoelephantopus spicatus (Juss.) Rohr. The hepatoprotective effects of water extracts of these three plants against beta-D-galactosamine (D-GalN)- and acetaminophen (APAP)-induced acute hepatic damage were determined in rats. The results indicated that the serum glutamate-oxalate-transaminase (sGOT) and the serum glutamate-pyruvate transaminase (sGPT) levels caused by D-GalN and APAP decreased after treatment with crude extracts of 'teng-khia-u' (P < 0.005). The pathological changes of hepatic lesions, caused by D-GalN and APAP, improved following treatment with the drug extracts mentioned above. PMID- 7776661 TI - Analgesic effect of Irvingia gabonensis stem bark extract. AB - Irvingia gabonensis is used medicinally in most parts of tropical Africa for the treatment of a number of ailments. In West Africa the Mende tribe of Sierra Leone uses the stem bark to relieve pain. In order to establish a pharmacological rationale for the traditional use of this plant as a remedy for pain, the water and ethanol extracts of the powdered stem bark were screened for analgesic activity and compared with standard analgesic drugs. The water extract and morphine protected the mice from heat-induced pain. In contrast, the ethanol extract and metamizole sodium showed very low level of analgesic activity in this test. However, using tail pressure as a source of pain, the water and ethanol extracts, metamizole sodium and morphine offered protection to the mice against pain stimuli. Morphine and the water extract were more potent as analgesic agents in heat than non-heat pain test. The analgesic effects of the water extract and morphine were blocked by a non-selective opioid receptor antagonist, naloxone in both tests, whereas the analgesic effects of the ethanol extract and metamizole sodium were not antagonized by the same dose of the opioid antagonist. The data presented in this study suggest that the active principle(s) in the water extract has analgesic profile similar to that of the narcotic analgesic and the ethanol extract might contain compound(s) that behave like non-narcotic analgesic agent. These findings provide for the first time the pharmacological basis for the folkloric use of Irvingia gabonensis in the relief of pain. PMID- 7776662 TI - Effects of stilbenes isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes. AB - Studies were made on the effects of stilbene derivatives isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes (PMN-L). Resveratrol (3,4',5-trihydroxystilbene) isolated from the roots of Reynoutria japonica was found to inhibit the 5-lipoxygenase products 5 hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), 5,12-dihydroxy-6,8,10,14 eicosatetraenoic acid (5,12-diHETE) and leukotriene C4(LTC4); its concentrations for 50% inhibition (IC50) were 8.90 x 10(-6) M, 6.70 x 10(-6) M and 1.37 x 10(-6) M, respectively. The IC50 of 5-HETE, 5,12-diHETE and LTC4 formations of synthetic 3,3',4-trihydroxystilbene were 5.90 x 10(-6) M, 6.30 x 10(-7) M and 8.80 x 10(-7) M, respectively. Moreover, they inhibited the release of lysosomal enzyme such as lysozyme and beta-glucuronidase induced by calcium ionophore A 23187 from human PMN-L at 10(-3)-10(-4) M. PMID- 7776663 TI - Prophylactic therapy of Salmonella typhi septicemia in mice with a traditionally prescribed crude drug formulation. AB - A crude drug formulation comprised of eight medicinal herb extracts was studied for in vitro and in vivo effect against Salmonella typhi. The formulation displayed inhibitory action against the test organism in vitro. Subsequently mice were challenged with a virulent strain of Salmonella typhi (Ty2) and the protective effect of the formulation was evaluated with post-infective, pre infective, single and multiple dose schedules, administered either orally or subcutaneously. A schedule that included multiple divided doses prophylactically administered had a significant therapeutic effect. PMID- 7776664 TI - Medicinal plants from Riau province, Sumatra, Indonesia. Part 1: Uses. AB - One hundred and fourteen species of flowering plants, claimed to have medicinal uses, were recorded from a previously uninvestigated area of Sumatra. Of the specimens, which belonged to 51 families, 50% were used to combat fever, 33% for diarrhoea and 31% for other gastrointestinal problems. External applications were often used to treat internal conditions, particularly fever. Species new to the ethnomedical literature are Garcinia parvifolia, Scleria purpurescens, Galearia filiformis, Litsea elliptica, Litsea robusta, Barringtonia lanceolata, Sesbania aculeata, Mimosa pigra, Abelmoschus ficulneus, Hedyotis leucocarpa, Pavetta multiflora, Symplocos cochinchinensis and Trema tomentosa. Hanguana (as H. malayana) represents a new genus of medicinal plants. PMID- 7776666 TI - Tricuspid valve replacement. Fifteen years of experience with mechanical prostheses and bioprostheses. AB - Tricuspid valve replacement is not a common operation. The purpose of this study was to examine the early and late results in 60 patients who underwent 28 (47%) bioprosthetic and 32 (53%) mechanical tricuspid valve replacements. All operations took place between January 1978 and June 1993 during which period a total of 4741 patients underwent valve replacement operation. Mean patient age was 50 +/- 15 (18 to 75) years. Forty-one patients (68%) were female and 19 patients (32%) were male. Forty-nine patients (82%) were in New York Heart Association class III or IV before operation. Forty-five patients (75%) were undergoing repeat cardiac valve operation. Seventeen patients (28%) had complex congenital cardiac problems. Operation was urgent in 15 patients (25%). The hospital mortality rate was 27% (16 patients). All patients with hospital death were in New York Heart Association class III or IV, were having repeat operations, or had complex congenital disease. Low output syndrome was observed in 21 patients (35%). Reoperation because of bleeding was required in seven patients (12%). Thirteen patients (22%) required permanent (epicardial lead) pacemaker implantation. Mean follow-up is 75 +/- 45 months (maximum 173 months) and 100% complete for the 44 patients who left the hospital. There have been 14 deaths (32%). Nine of these patients (64%) had mechanical valves and five (36%) had bioprostheses. Of the 11 cardiac deaths, three were valve related (bioprostheses). Three patients (10%) required reoperation because of tricuspid valve prosthetic failure (1 thrombosed mechanical valve, 2 failed porcine valves). Of the remaining 30 patients, 20 (67%) are in New York Heart Association class I or II. Seventeen patients have mechanical valves and 13 have bioprostheses. Twenty-six patients (90%) are receiving warfarin. Thromboembolism (transient ischemic attack) has occurred in one patient with a mechanical valve who also had a previous cerebrovascular accident. In this group there has been no hemorrhage, endocarditis, or new pacemaker requirement. Actuarial survival for the whole series is 37% +/- 9% and for the hospital survivors is 50% +/- 12% at 15 years. Linearized rates of valve-related complications are not different between groups. Tricuspid valve replacement is a beneficial procedure for patients with structural tricuspid valve disease, many of whom have other valvular or congenital disease. Contemporary mechanical prostheses and bioprostheses are equally effective in the tricuspid position. Mechanical valves should be considered for tricuspid replacement in young patients and in patients with mechanical valves implanted in the left side of the heart. PMID- 7776665 TI - Medicinal plants from Riau province, Sumatra, Indonesia. Part 2: Antibacterial and antifungal activity. AB - Antibacterial assays of 114 species listed in Part 1 showed that 82% of the extracts tested were active against Staphylococcus aureus, while 35% were active against Escherichia coli. Antifungal activity was less dramatic: 19% of the extracts inhibited Saccharomyces cerevisiae, while 20% inhibited Fusarium oxysporum. Our survey of relevant literature indicates that less than 30% of these Angiosperm species have previously been assayed for any form of antimicrobial activity. PMID- 7776667 TI - Reimplantation of the right internal thoracic artery as a free graft into the left in situ internal thoracic artery (Y procedure). One-year angiographic results. AB - Reimplantation of the right internal thoracic artery, as a free graft, into the left in situ internal thoracic artery (Y procedure) has enabled us to bypass more distant marginal vessels, which was not possible by the bilateral technique alone. This prospective study was aimed at evaluating the clinical state of the patients and the degree of patency of grafts within 16 months of follow-up. All 80 patients who underwent the Y procedure between January 1988 and January 1992 were included. This group represented 10% of the 840 patients having coronary bypass during the same period. A total of 202 coronary anastomoses were performed in this series. Early postoperative (30 days) complications included three deaths (3.75%), eight myocardial infarctions (10%), one case of phrenic nerve paralysis (1.25%), two cases of respiratory failure (2.5%), and six wound infections (7.5%). At 3 months' follow-up, 96% of patients were free of symptoms. During the follow-up period, four patients died of noncardiac causes (lung, pancreatic, and brain cancer and rupture of an abdominal aortic aneurysm). At 1 year, 71 patients were free of symptoms (97%). Sixty-one patients underwent coronary angiography between 12 and 24 months. Six patients with peripheral arterial disease were not suitable for coronary angiography, and six refused to be tested. These 12 patients had normal thallium test results in the bypassed area (stress or dipyridamole test). The patency rate of the left internal thoracic artery was 98.3% (n = 60), occlusion rate 1.6% (n = 1), and incidence of threadlike arteries 4.9% (n = 3). Thus the rate of perfect patency was 93.4%. The patency rate of the right internal thoracic artery as a free graft was 93.4% (n = 57), occlusion rate 6.5% (n = 4), and the incidence of threadlike arteries 8% (n = 5). Thus the rate of perfect patency was 85.2%. A total of 169 anastomoses were studied. The rate of patency of the anastomoses to the left anterior descending coronary artery was 96% (n = 58) and the occlusion rate, 4% (n = 2). The patency rate of sequential anastomoses (side to side) to diagonal arteries was 100% (n = 16). Patency rate of anastomoses to obtuse marginal arteries was 95% (n = 58) and the rate of occlusion, 4.9% (n = 3). The patency rate of anastomoses to the posterior descending artery or distal branches of the right coronary artery was 80% (n = 4/5).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776668 TI - Modified conduit preparation creates a pseudosinus in an aortic valve-sparing procedure for aneurysm of the ascending aorta. AB - Mechanical valved conduit replacement of the aortic root is a durable and appropriate procedure for many diseases of the ascending aorta, but may sacrifice an anatomically salvageable aortic valve. For young active patients and for patients with "systemic" arterial disease (atherosclerosis, Marfan's syndrome) who may require future operations, life-long anticoagulation with its attendant thromboembolic versus hemorrhagic risks is not ideal. Several techniques have been suggested as aortic valve-sparing options. Recently, a procedure was described that combines the freehand homograft techniques with the standard Bentall techniques (David procedure). This innovative technique replaces the ascending aorta with a Dacron cylinder, spares the aortic valve, and restores competence and thus offers an excellent alternative. The durability of this procedure that places the aortic valve inside a cylindrical conduit without sinuses of Valsalva is unknown. In selected patients, we have used this technique to spare the aortic valve. On the basis of experimental data and preliminary computer modeling, with the hope of improving the durability, we have modified the conduit to create a "pseudosinus" in our most recent nine patients. We have done the David procedure in 10 patients. The pseudosinus modification was done in the most recent nine patients. Patients' ages ranged from 37 to 71 years (mean 49.9 years). There were five female and five male patients. Five patients had Marfan's syndrome and five patients had annuloaortic ectasia. There has been no mortality and all patients have had both early and late follow-up echocardiography. Five patients have zero to trace aortic insufficiency, four patients have trace to mild aortic insufficiency, and one patient has mild or "1+" aortic insufficiency. Aortic insufficiency has not progressed in any patient during the 18 months of follow-up. The patient with 1+ aortic insufficiency has no activity limits, good ventricular function, and no evidence of congestive symptoms. One patient who had extensive thoracoabdominal aneurysmal disease has undergone subsequent replacement of the descending aorta to the level of the renal arteries and has done well. Aortic valve-sparing replacement of the aortic root is an excellent procedure for any patient with an ascending aortic aneurysm and an anatomically salvageable valve. We believe that by modifying the proximal conduit and creating a "pseudosinus" into which the leaflets can retract without contact of the cylindrical conduit we may increase the longevity of the native aortic valve in this procedure. PMID- 7776669 TI - Growth and fibrinolytic parameters of human umbilical vein endothelial cells seeded onto cardiovascular grafts. AB - It was the aim of this study to investigate possible effects of biomaterials used to produce vascular grafts on the fibrinolytic system of endothelial cells. Therefore growth conditions for human umbilical vein endothelial cells on polytetrafluoroethylene and on polyurethane were optimized. Tissue culture polystyrene was used as a control material. We could demonstrate that precoating of the materials with fibronectin significantly increased the growth rate of human umbilical vein endothelial cells on these materials. Furthermore, we showed that human umbilical vein endothelial cells grown on polytetrafluoroethylene or polyurethane released more plasminogen activator inhibitor-1 and tissue type plasminogen activator into the conditioned media than did human umbilical vein endothelial cells grown on tissue culture polystyrene. Human umbilical vein endothelial cells cultured on polytetrafluoroethylene also deposited more plasminogen activator inhibitor-1 into the extracellular matrix than did control cells grown on tissue culture polystyrene. Our results give evidence that human umbilical vein endothelial cells grown on two biomaterials used to construct vascular grafts, namely polytetrafluoroethylene and polyurethane, produce tissue type plasminogen activator as well as plasminogen activator inhibitor-1, two major components of the fibrinolytic system also expressed by endothelial cells in vivo. In conclusion, our data suggest that endothelial cells grown on vascular grafts show functional integrity concerning their fibrinolytic system, which in turn might contribute to reduce the thrombogenic properties of the graft material. PMID- 7776670 TI - Transvenous versus transthoracic cardioverter-defibrillator implantation. A comparative analysis of morbidity, mortality, and survival. AB - The hypothesis that transvenous implantation of a cardioverter-defibrillator is associated with less morbidity than use of a transthoracic approach was investigated in a retrospective series of 146 patients. None of these patients had concomitant heart procedures, and the preoperative characteristics of the two groups were similar. When analyzed by actual technique used (transvenous, 57 patients; transthoracic, 89 patients) and by the intention-to-treat method (transvenous, 65 patients, 8 of whom actually underwent thoracotomy; thoracotomy, 81 patients), transvenous implantation was associated with a lower incidence of postoperative respiratory complications and atrial fibrillation. Total cardiac mortality and freedom from sudden cardiac death in the transvenous and transthoracic groups were comparable at 2 years. PMID- 7776671 TI - Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs. AB - Lung transplantation is limited by a shortage of suitable donors. To address this shortage, we have begun using donor lungs that do not meet all of our previous rigorous donor criteria. Of 133 consecutive lung transplants done between June 1991 and March 1994, 89 donors were considered ideal because they satisfied all of the following accepted donor criteria (group I): age younger than 55 years, smoking less than 20 pack-years, arterial oxygen tension greater than 300 mm Hg (using inspired oxygen fraction of 1.0 and positive end-expiratory pressure 5 cm H2O), and chest radiograph negative for infiltrate or trauma (contusion or pneumothorax). Thirty-seven donors failed to satisfy one of these criteria and seven donors failed to satisfy two of them, yielding 51 criteria denoting marginal status in the 44 donors in the marginal group (group II) as follows: age older than 55 years, 2; smoking history 20 or more pack-years, 9; unsatisfactory chest radiograph, 34; and arterial oxygen tension less than 300 mm Hg, 6. Sixty three single lung transplants were done (group I, 44 versus group II, 19) compared with 70 bilateral sequential transplants (group I, 45 versus group II, 25). In 24 cases in group II, at least one of the lungs actually being implanted contained contusion or infiltrate. Evaluation of recipients from the two groups showed no significant difference in median duration of postoperative mechanical ventilation (3 days in both group I and group II) nor in alveolar-arterial oxygen gradient immediately after transplantation (group I, 304 +/- 14 mm Hg versus group II, 275 +/- 22 mm Hg; p = 0.266) or at 24 hours (group I, 125 +/- 12 mm Hg versus group II, 122 +/- 18 mm Hg; p = 0.933) (all values represent mean plus or minus the standard error). However, cardiopulmonary bypass was required to facilitate second graft insertion in bilateral sequential transplants more often in the marginal group (5 of 25, 20%) than in group I (6 of 45, 13%). There were three deaths within 30 days in group I (operative mortality, 3.4%) and none in group II. Currently, 74 (83.2%) of 89 remain alive in group I compared with 38 (86.4%) of 44 in group II. On the basis of these data, we conclude that successful outcome of lung transplantation can be achieved with the use of marginal donor lungs. PMID- 7776672 TI - Cardiac transplant coronary artery disease. A multivariable analysis of pretransplantation risk factors for disease development and morbid events. AB - Coronary artery disease after cardiac transplantation is a major obstacle to long term survival. The development and progression of coronary artery disease after cardiac transplantation was analyzed in 217 consecutive patients undergoing transplantation. The actuarial freedom from any coronary artery disease (by angiography or autopsy) was 81% at 2 years and 20% at 8 years after transplantation. Coronary artery disease was more prevalent in male than female patients (30% versus 50% free of coronary artery disease at 5 years, p = 0.01). By multivariable analysis, pretransplantation risk factors identified for coronary artery disease included pretransplantation positive cytomegalovirus serologic status of the recipient (p = 0.002) and older donor age (p = 0.07). Progression of coronary artery disease was variable in both time of onset and rate. Earlier detection did not result in more rapid progression. Coronary events severe enough for retransplantation (n = 8) and/or death from coronary artery disease (n = 9) occurred in 15 patients, of whom four underwent retransplantation. The actuarial freedom from coronary events was 88% at 5 years and 79% at 8 years. By multivariable analysis, only male recipient (p = 0.05) was a risk factor for coronary events. Seven of the 15 patients (47%) with coronary events died suddenly of coronary artery disease without prior angiographic evidence of severe coronary disease. Coronary artery disease is progressive. Improved surveillance methods are required to detect the disease and institute timely intervention to prevent the occurrence of unanticipated death. PMID- 7776674 TI - Successful survival of primates receiving transplantation with "dead," nonbeating donor hearts. AB - A paucity of donor organs is the principal limitation in human heart transplantation. Prompted by our short-term studies of reanimating "dead" donor hearts in sheep, we applied the same reperfusion modifications in juvenile baboons to determine human applications in an anoxic arrest model (as occurs when non-brain-dead patients are extubated and allowed to die). Ten juvenile baboons (mean weight 3.6 kg) were studied. Five baboons were used as donors. After being anesthetized, donors were pretreated with methylprednisolone (Solu-Medrol), 50% dextrose, nifedipine, and prostaglandin E1 and then paralyzed and extubated. Donors became pulseless at 7 +/- 1 minutes and had electric arrest 9 to 18 minutes after paralysis. The five donors were left undisturbed and warm for 15, 22, 30, 30, and 31 minutes, respectively, after asystole. They were then given 250 ml of 4 degrees C Roe's crystalloid cardioplegic solution via the aortic root and the hearts were explanted into iced Euro-Collins solution. Five baboons served as recipients. After donor harvest, recipients were placed on cardiopulmonary bypass, given prostaglandin E1, and cooled to 18 degrees C; circulatory arrest was instituted and the recipient's heart excised. The donor heart was transplanted in an orthotopic position. Before reinstitution of bypass, 250 ml of terminal leukocyte-depleted blood cardioplegic solution was given, then bypass was restarted and the hearts were reperfused for 60 minutes. All animals were weaned from bypass without the use of inotropic agents. All animals were extubated within 2 to 4 hours after bypass and received standard immunosuppression. Peak creatine kinase MB/total creatine kinase ratio was 0.2% +/- 0.2%. Postoperative ejection fractions by echocardiography were 75% to 80% (mean 76%). Animals survived 1, 9, 13, 16, and 34 days, with three deaths caused by acute rejection and one each by stroke and diarrhea/dehydration. Pathologic findings showed no areas of fibrosis or ischemic damage. We conclude that successful reanimation and engraftment can be achieved with the use of the asystolic primate heart; this work suggests that human application is realistic and could greatly expand the donor pool. PMID- 7776673 TI - Impact of initial flush potassium concentration on the adequacy of lung preservation. AB - The effects of initial lung flushing with intracellular and extracellular fluid type solutions were studied in lungs stored with the University of Wisconsin solution. Excised Sprague-Dawley rat lungs (n = 39) were flushed first with one of the following solutions: (1) the University of Wisconsin solution (K+ = 140 mmol/L), (2) modified (low potassium) University of Wisconsin solution (K+ = 20 mmol/L), (3) phosphate buffered saline solution (K+ = 3.9 mmol/L), (4) modified low-potassium phosphate-buffered saline solution (K+ = 20 mmol/L), (5) modified high-potassium phosphate-buffered saline solution (K+ = 40 mmol/L), and (6) Euro Collins solution (K+ = 115 mmol/L) followed by secondary flush with storage solution and cold (4 degrees C) storage in University of Wisconsin solution for 24 hours. The lungs were then reperfused in the isolated, pulsatile, blood perfused working lung system for 2 hours or until lung failure. Blood gas analysis and shunt fraction, aerodynamic parameters (airway resistance, lung compliance, elastic work, and flow resistive work), and total pulmonary vascular resistance were measured throughout the perfusion period. The mean oxygen tensions (in millimeters of mercury) at 30 minutes after the onset of reperfusion for University of Wisconsin solution, modified University of Wisconsin solution, phosphate-buffered saline solution, modified phosphate-buffered saline solutions (20 and 40 mmol/L), and Euro-Collins solution were 56.1 +/- 4.2, 72.7 +/- 9.1, 87.7 +/- 6.9 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 86.0 +/- 9.6 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), 87.9 +/- 7.7 (p < 0.01 versus University of Wisconsin solution; p < 0.01 versus Euro-Collins solution), and 53.5 +/- 6.0, respectively. All aerodynamic parameters in the lungs flushed with extracellular fluid type solutions were superior to those flushed with intracellular fluid type solutions. We conclude that the efficacy of initial flushing was essential for successful lung preservation and that extracellular fluid type solutions were superior to intracellular fluid type solutions, at least for flushing the lung before storage with University of Wisconsin solution. Potassium concentration in flushing solution should be 20 mmol/L or less to obtain appropriate flushing and subsequent adequate distribution of the storage solution. PMID- 7776675 TI - Characteristics of patients surviving more than ten years after cardiac transplantation. AB - The clinical status and quality of life of 40 patients who lived or are still alive more than 10 years after transplantation at our institution were reviewed with the use of our transplant database, prospective patient examinations, cardiac catheterization, and exercise testing. Patient-perceived health status was determined with use of the Nottingham Health Profile and General Well Being examinations. Factors associated with longevity were determined by a Cox proportional hazards model. Twenty-six patients are alive and 14 have died. The mean age at transplant was 32.4 +/- 12 years and the current age (or age at death) is 46.1 +/- 12.8 years. Actuarial freedom from rejection was similar to that of patients surviving less than 10 years (p = 0.8), but freedom from all types of infection was less (p = 0.005). Immunosuppressive drugs include cyclosporine (11/26 patients), azathioprine (24/26), and prednisone (26/26, mean dose 12.7 mg/day). Catheterization hemodynamic data show well-preserved graft function at a mean follow-up of 11.7 +/- 3.3 years. Graft coronary artery disease prevalence is 51.0% +/- 8%. Exercise test results are as follows: duration 8.7 +/ 3.5 minutes (range 2 to 16 minutes), maximum heart rate/expected rate 77.3% +/- 11% (50% to 92%), maximum systolic blood pressure 171 +/- 23 mm Hg (140 to 208 mm Hg), and metabolic equivalents 9.2 +/- 2.3 units (5.5 to 12.9 units), or about 84% of predicted. Mean score on the General Well Being examination was 75.3 +/- 21.6 (normal). Nottingham Health Profile scores were nearly normal, except for in the 50- to 64-year-old age group in categories of mobility, pain, sleep quality, and energy level. Causes of death were coronary artery disease in 7 of 14, infection in 4 of 14, lymphoma in 1 of 14, and nonlymphoid cancer in 2 of 14. In the Cox regression, variables most associated with survival (t > 2.0, multivariate p = 0.0005) were age at transplantation (t = 3.26), preoperative duration of illness (t = 3.57), postoperative cytomegalovirus infection (t = 2.16), and ejection fraction at 12 months after operation (t = -2.62). We conclude that cardiac transplantation can provide patients with end-stage cardiac failure an acceptable general medical condition, functional status, and perceived quality of life well into the second decade after operation. PMID- 7776677 TI - The pumping and left ventricular unloading capabilities of the ventricular synchronous skeletal-muscle ventricle. AB - The pumping and left ventricular unloading capabilities of the left ventricular, ventricular synchronous skeletal-muscle ventricle were determined in nine anesthetized dogs ranging in weight from 20.7 to 31.8 kg. The ventricular synchronous skeletal-muscle ventricle consists of the left rectus abdominis muscle wrapped around a 4-mil-thick polyethylene pouch (wrapped volume 80 to 100 ml) connected to the left ventricular apex with no valve and to the aorta via a prosthetic heart valve. The rectus muscle is timed to contract tetanically and relax during left ventricular ejection. This arrangement provides a high precontraction pressure for the rectus muscle and a high muscle capillary blood flow during skeletal muscle relaxation. The timing signal for initiation of the train of stimulating pulses (40/sec) was derived from the ventricular electrogram. The delay for the stimulus train determines the preload for the rectus muscle and along with the stimulus train duration determines ventricular synchronous skeletal-muscle ventricle stroke volume, which was measured by electric impedance. With unconditioned rectus muscles (70 to 120 gm) and with a pumping ratio of 1:3, ventricular synchronous skeletal-muscle ventricle stroke volume average 26.1 ml, which provided an average output of 876 ml/min. The normalized ventricular synchronous skeletal-muscle ventricle output was 35.6 ml/min per kilogram of body weight. In a typical resting dog (and man), the normalized cardiac output is 70 ml/min per kilogram. Therefore the ventricular synchronous skeletal-muscle ventricle is capable of pumping 52% of the cardiac output (with a pumping ratio of 1:3). The optimum train delay from the apex of the ventricular electrogram ranged from 10 to 100 msec. The left ventricular ejection period averaged 309 msec, and this determines the time available for the rectus muscle to contract and relax. Evidence for unloading the left ventricle is shown by the reduced left ventricular diastolic pressure and stroke volume for the postassisted beats. PMID- 7776676 TI - Retrograde cardioplegia does not adequately perfuse the right ventricle. AB - Surgeons often rely primarily on retrograde cardioplegia for myocardial protection, because it provides adequate left ventricular perfusion even in the presence of coronary artery disease. Clinically, however, adequate right ventricular perfusion by retrograde delivery has not been demonstrated. Using intraoperative transesophageal echocardiography, we examined retrograde delivery of cardioplegic solutions by contrast echocardiography, which directly assesses myocardial perfusion. In 15 patients (seven having coronary bypass and eight having valve operations), 4 ml of sonicated Isovue medium was injected retrograde via a coronary sinus catheter. Myocardial perfusion was assessed quantitatively by visual inspection and back-ground-subtracted videodensitometric analysis. In five patients undergoing aortic valve replacement, right and left coronary ostial drainage was estimated during retrograde infusion. Before the aortic crossclamp was removed, myocardial oxygen extraction was calculated in all 15 patients by first delivering warm blood cardioplegic solution for 2 minutes in a retrograde fashion and then taking samples from the cardioplegia line and aortic root. This determined the oxygen extraction ratio across the myocardium at the end of retrograde delivery. Warm blood cardioplegic solution was next given antegrade, and 15 seconds later samples were taken from the cardioplegia line and a right ventricular (acute marginal) vein to determine the oxygen extraction ratio across the right ventricle. As assessed by contrast echocardiography, retrograde infusion resulted in almost four times more perfusion to the left ventricular free wall and septum than to the right ventricular free wall (74 +/- 2 versus 69 +/- 2 versus 20 +/- 2, p < 0.05). In those five patients with an aortotomy the right ostial drainage was less than 5 ml/min whereas left ostial drainage was estimated at 80 ml/min during retrograde administration. Oxygen extraction across the myocardium supplied by retrograde infusion was low after 2 minutes. Conversely, when antegrade cardioplegia was started, right ventricular oxygen extraction rose fourfold (42% +/- 5% versus 11% +/- 1%, p < 0.05), demonstrating that retrograde cardioplegia had not adequately perfused the right ventricular myocardium. CONCLUSIONS: 1. Retrograde cardioplegia provides poor right ventricular myocardial perfusion as assessed by contrast echocardiography and coronary ostial drainage. (2) This poor perfusion is inadequate to meet myocardial demands as demonstrated by the high right ventricular oxygen extraction after a prolonged retrograde infusion. (3) Therefore surgeons must not rely solely on retrograde cardioplegia for right ventricular myocardial protection. This concept is especially important if continuous warm blood cardioplegia is used, because myocardial requirements are then higher. PMID- 7776678 TI - The influence of leukocyte filtration during cardiopulmonary bypass on postoperative lung function. A clinical study. AB - The accumulation of activated leukocytes in the pulmonary circulation plays an important role in the pathogenesis of lung dysfunction associated with cardiopulmonary bypass. Animal studies have demonstrated that the elimination of leukocytes from the circulation reduces postoperative lung injury and improves postoperative pulmonary function. We conducted a prospective randomized clinical study to evaluate whether postoperative lung function could be improved by use of a leukocyte filter during cardiopulmonary bypass. Elective coronary artery bypass grafting was done with a leukocyte-depleting arterial blood filter incorporated in the extracorporeal circuit (14 patients, leukocyte filter group) or without the filter (18 patients, control group). Blood samples collected at intervals before, during, and after operation were used for analysis of blood cell counts, elastase concentrations, and arterial blood gases. The use of the leukocyte filter caused no significant reduction in leukocyte count (p = 0.86). There were no differences in postoperative lung function between the groups, as assessed through (1) oxygenation index (290 for leukocyte filter group compared with 329 for control group, 95% confidence interval, 286 to 372, p = 0.21), (2) pulmonary vascular resistance (p = 0.10), and (3) intubation time (16.6 hours for leukocyte filter group versus 15.7 hours for control group, 95% confidence interval, 12.1 to 19.1 hours, p = 0.72). The levels of neutrophil elastase were significantly higher at the end of cardiopulmonary bypass in the leukocyte filter group (460 microgram/L in leukocyte filter group versus 230 microgram/L in control group, 95% confidence interval, 101 to 359 microgram/L, p = 0.003). We conclude that the clinical use of the present form of leukocyte-depleting filter did not improve any of the postoperative lung function parameters analyzed in this study. PMID- 7776679 TI - Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. AB - This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4 degrees C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 mumol/L SPM-5185 (low-dose group; n = 6), or 10 mumol/L SPM-5185 (high-dose group; n = 6). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 60 minutes, first in the beating empty state for 30 minutes and then after discontinuation of bypass for 30 minutes. Baseline and postischemic left ventricular function was assessed by the slope of the end-systolic pressure volume (impedance catheter) relation. Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preischemic values in the vehicle group (from 8.2 +/- 1.0 to 3.8 +/- 0.3 mm Hg/ml) and by 33.7% (from 9.2 +/- 1.1 to 6.1 +/- 0.5 mm Hg/ml) in the low-dose group. In contrast, there was complete postischemic functional recovery in the high-dose group (from 7.6 +/- 1.1 to 7.2 +/- 1.2 mm Hg/ml). In coronary arteries isolated from these hearts, endothelium-dependent maximal relaxation to acetylcholine was impaired by 27% in the vehicle group and by 18% in the low-dose group, whereas the high-dose group showed complete endothelium-dependent relaxation. Myeloperoxidase activity, an index of neutrophil accumulation in postischemic myocardium, was elevated in the vehicle and low-dose groups (3.36 +/- 0.58 and 2.56 +/- 0.68 U/100 mg tissue) but was significantly reduced in the high-dose group to 1.27 +/- 0.45 U/100 mg tissue. We conclude that inclusion of 10 mumol/L nitric oxide donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly via inhibition of neutrophil mediated damage. PMID- 7776680 TI - A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia. AB - This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart. PMID- 7776681 TI - Pharmacologic intervention for ischemic brain edema after retrograde cerebral perfusion. AB - Retrograde cerebral perfusion has recently been the focus of interest as a simple new technique of brain protection during aortic arch operations. We undertook the experimental protocol of 120 minutes of retrograde cerebral perfusion followed by antegrade reperfusion. Eighteen mongrel dogs were used. Retrograde cerebral perfusion was maintained at a flow rate of 150 to 250 ml/min to keep the perfusion pressure from 15 to 25 mm Hg. Animals were divided into three groups as follows: in group I, no treatment was received during and after retrograde cerebral perfusion; in group II, mannitol (2 gm/kg) was administered before cardiopulmonary bypass was restarted; and in group III, antivasospastic substance (1,2-bis nicotinamido]-propane) was continuously injected during and after retrograde cerebral perfusion (1 mg/kg per minute). Cerebral blood flow decreased during retrograde cerebral perfusion in all three groups. Cerebrovascular resistance showed marked increases 30 and 60 minutes after cardiopulmonary bypass was restarted in group I compared with the values in groups II and III (group I: 3.35 +/- 0.73 and 5.00 +/- 1.57 mm Hg/ml per 100 gm per minute; group II: 1.30 +/ 0.33 and 1.03 +/- 0.17 mm Hg/ml per 100 gm per minute; group III: 1.24 +/- 0.41 and 0.98 +/- 0.24 mm Hg/ml per 100 gm per minute). The oxygen extraction level was reduced by cooling, but it rose to a higher level as a result of significant desaturation of returned blood even in deep hypothermia during retrograde cerebral perfusion. Both cerebral metabolic rate of oxygen and cerebral metabolic rate of glucose remained at low levels during retrograde cerebral perfusion. Ratios of cerebral blood flow to cerebral metabolic rate of oxygen and cerebral blood flow to cerebral metabolic rate of glucose were markedly reduced during retrograde cerebral perfusion. Intracranial pressure showed significant increases 30 and 60 minutes after cardiopulmonary bypass was restarted in group I compared with values in group II or group III (group I: 22.7 +/- 2.8 and 20.6 +/- 5.1 mm Hg; group II: 6.3 +/- 1.8 and 5.3 +/- 1.3 mm Hg; group III: 4.2 +/- 1.7 and 7.7 +/- 2.8 mm Hg). Water content of the brain tissue in group I (77.54% +/- 0.29%) was significantly higher than that in group II (74.71% +/- 0.76%) or group III (74.14% +/- 0.48%). These data suggest that the supply of oxygen or glucose by retrograde cerebral perfusion is not enough to maintain sufficient cerebral metabolism, which may cause brain edema during antegrade reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776682 TI - Pulmonary resection for invasive Aspergillus infections in immunocompromised patients. AB - Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear. PMID- 7776683 TI - Safety and efficacy of video-assisted thoracic surgical techniques for the treatment of spontaneous pneumothorax. AB - Video-assisted thoracic surgery has been widely used in the treatment of spontaneous pneumothorax despite a paucity of data regarding the relative safety and long-term efficacy for this procedure. We reviewed 113 consecutive patients (68 male and 45 female patients, aged 15 to 92 years, mean 35.1) who underwent 121 video-assisted thoracic surgical procedures during 119 hospitalizations from 1991 through 1993. Recurrent ipsilateral pneumothorax was the most frequent indication for surgery and occurred in 77 patients (65%). The most common method of management was stapling of an identified bleb in the lung, which was undertaken in 105 (87%) patients. No operative deaths occurred. Complications included an air leak lasting longer than 5 days in 10 (8%) patients, two of whom required second procedures for definitive management. No episodes of postoperative bleeding or empyema occurred. The postoperative stay ranged from 1 day to 39 days (median 3 days, average 4.3 days) and 99 patients (84%) were discharged within 5 days. Mean follow-up was 13.1 months and ranged from 1 to 34 months. Eleven patients (10%) were lost to follow-up. Ipsilateral pneumothorax recurred after five of 121 procedures (4.1%). Twelve perioperative parameters (age, gender, race, smoking history, site of pneumothorax, severity of pneumothorax, operative indications, number of blebs, site of blebs, bleb ablation, method of pleurodesis, and prolonged postoperative air leak) were entered into univariate and multivariate analysis to identify significant independent predictors of recurrence. The only independent predictor of recurrence was the failure to identify and ablate a bleb at operation, which resulted in a 23% recurrence rate versus a 1.8% rate in those with ablated blebs (p < 0.001). These data suggest that video-assisted thoracic surgery is a viable alternative to thoracotomy for the treatment of recurrent spontaneous pneumothorax. It results in a short hospital stay, low morbidity, high patient acceptance, and a low rate of recurrence. PMID- 7776684 TI - Immunohistochemical detection of P53 protein is not associated with a poor prognosis in non-small-cell lung cancer. AB - Immunohistochemical detection of the p53 gene product by monoclonal antibodies has been shown to be associated with a poor clinical outcome in carcinomas of the breast and stomach. Because the prognostic relevance of p53 immunostaining in lung cancer is still under debate, we studied the expression pattern and clinical significance of such staining in 73 patients with operable non-small-cell lung cancer. p53 expression was detected on frozen sections with the use of monoclonal antibody p1801, which recognizes both the wild-type and mutant gene product (alkaline phosphatase-anti-alkaline phosphatase method). A tumor was considered p53 positive if more than 1% of the tumor cells were stained. The p53 expression pattern was compared with clinicopathologic parameters, and analysis of follow up, based on the data of 65 patients, was done by a log rank test (median observation time, 780 days). Nuclear p53 staining was detected in 33 of 73 non small-cell lung cancers (45.2%). Comparison with clinicopathologic parameters demonstrated that the p53 protein was detected more frequently in younger patients (younger than 50 years, p = 0.014), whereas no correlation was found with sex, tumor differentiation, tumor histologic type, or TNM stage. Surprisingly, follow-up analysis revealed that p53 staining was associated with an increased rate of disease-free survival, especially in patients with early stage tumor disease (p = 0.004) and in male patients (p = 0.023). Counter to previous studies in other solid tumors, immunocytochemical detection of p53 expression does not predict a poor clinical outcome in non-small-cell lung cancer. In early-stage lung cancer it might be associated with an improved disease-free survival, which suggests that the majority of the detected protein inherits the wild-type tumor suppressor function. PMID- 7776685 TI - Immunotherapy with the use of tumor-infiltrating lymphocytes and interleukin-2 as adjuvant treatment in stage III non-small-cell lung cancer. A pilot study. AB - This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating does for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease. PMID- 7776686 TI - Pulmonary vascular resistance during exercise late after repair of large ventricular septal defects. Relation to age at the time of repair. AB - Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 +/- 3.6) in group 1 and 0.8 to 15.8 years (4.3 +/- 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 +/- 3.0) in group 1 and 9 to 22 years (13.5 +/- 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 +/- 2) and 10 to 26 mm Hg (20 +/- 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 +/- 3) and 14 to 39 mm Hg (27 +/- 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U.m2 (1.93 +/- 0.63) and 0.79 to 3.31 U.m2 (2.05 +/- 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U.m2 (1.36 +/- 0.57) and 0.81 to 3.85 U.m2 (2.18 +/- 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years. PMID- 7776687 TI - The relationship of the outlet septum to the aortic outflow tract in hearts with interruption of the aortic arch. AB - We examined 13 hearts with concordant atrioventricular and ventriculoarterial connections and interruption of the aortic arch to establish and describe the morphologic features of the outflow tracts in relation to axial deviation and malalignment of the outlet septum as opposed to overriding of the arterial valvular orifices. Interruption in all cases but one was between the left common carotid and left subclavian arteries; the other arch was interrupted at the isthmus. A patent arterial duct and ventricular septal defect were universally present. When its borders were viewed from the right ventricle, the ventricular septal defect was perimembranous in seven hearts, had exclusively muscular borders in four hearts, and was doubly committed and juxta-arterial in the remaining two hearts. Malalignment between the muscular ventricular septum and outlet septum, or a fibrous raphe, as judged when the heart was viewed in its short axis, was found in 12 of the hearts. Posterior and leftward axial deviation of the outlet septum in its long axis was found in 4 of the 12 hearts and also in one heart that did not have short-axis malalignment. Attachments of the leaflets of the pulmonary valve in both right and left ventricles, however, were present in only one of the specimens, this being a case with a doubly committed and juxta arterial defect. These separate features of the outflow tract in hearts with interruption of the aortic arch, therefore, require thorough assessment when surgical management is planned. All these variable features can be assessed preoperatively by cross-sectional echocardiography, which should be directed toward defining the degree of development and alignment of the outlet septum, as well as the length of the subpulmonary infundibulum. PMID- 7776689 TI - Spinal cord protection during thoracoabdominal aneurysm resection. PMID- 7776688 TI - The modified Fontan operation. An analysis of risk factors for early postoperative death or takedown in 702 consecutive patients from one institution. AB - To better understand risk factors associated with early postoperative death or failure, we reviewed our entire experience with 702 consecutive patients who had the modified Fontan operation at the Mayo Clinic between October 1973 and December 1989. The event rate for takedown of repair or death during the initial hospitalization or within 30 days of the operation was 14.8% (successful takedown of the repair, n = 6; death, n = 98). To identify variables associated with early death or Fontan takedown, we analyzed 33 clinical and hemodynamic variables in a univariate and multivariate manner. On the basis of a stepwise logistic discriminant analysis, patients who were younger and operated on before 1980 with a higher preoperative pulmonary artery mean pressure, asplenia, higher intraoperative (after Fontan operation) right atrial pressure, longer aortic crossclamp time, and pulmonary artery ligation were more likely to have the outcome event of interest (p values < 0.05). A new variable, corrected pulmonary artery pressure (that is, mean preoperative pulmonary artery pressure divided by the ratio of pulmonary to systemic flow if the ratio of pulmonary to systemic flow is greater than 1.0), was significantly associated with the outcome event univariately (p = 0.002), but was no more predictive than the preoperative pulmonary artery mean pressure. Variables less predictive of the outcome event in this analysis included multiple prior operations, polysplenia syndrome, complex anatomy other than asplenia syndrome, and systemic atrioventricular valve regurgitation. These results represent the largest single-institution review of the Fontan operation and suggest that some anatomic and hemodynamic variables previously predictive of poor early outcome have been nullified by current operative methods. PMID- 7776690 TI - Successful operation for solitary fibrous tumor of the epicardium. PMID- 7776691 TI - Right atrial myxoma originating from the tricuspid valve. PMID- 7776692 TI - The effects of the rate of reoxygenation on the recovery of hypoxemic hearts. PMID- 7776693 TI - Impact of nitric oxide inhalation on right ventricular failure after implantation of Novacor left ventricular assist system. PMID- 7776694 TI - Malfunctioning of vascular staple cutter during thoracoscopic lobectomy. PMID- 7776695 TI - Fibrous tissue ring: an uncommon cause of severe prosthetic valve stenosis. PMID- 7776696 TI - Polyradiculoneuritis as an initial manifestation of bronchial carcinoma. PMID- 7776697 TI - Minimizing chest wall trauma in video-assisted thoracic surgery. PMID- 7776698 TI - Solitary coronary ostium and aberrant coursing left coronary arteries: unfavorable anatomic anomaly in a case of aortic valve replacement. PMID- 7776699 TI - Primary elective open sternum with only Steri-Drape film coverage after cardiac operations in pediatric patients. PMID- 7776700 TI - Infections and pathologic factors in the donor lung. PMID- 7776701 TI - Modified Senning operation for cavopulmonary connection with autologous tissue. PMID- 7776702 TI - N-acetyl-beta-D-glucosaminidase activity within BAL from macaques exposed to generic coal dusts. AB - N-acetyl-beta(beta)-D-glucosaminidase is a lysosomal enzyme secreted by alveolar macrophages in response to phagocytosis of particulate material. Alveolar macrophages participate in the degradation and fibrosis of pulmonary tissue that results in pneumoconiosis. Known quantities of four characterized respirable dusts were bronchoscopically placed into the right caudal lung lobe of macaque monkeys. Bronchoalveolar lavage (BAL) samples were collected from dust-exposed right lung and unexposed left lung of the same individuals at 2-week intervals for 12 weeks after dust instillation. The samples were tested for N-acetyl-beta-D glucosaminidase activity to determine if the enzyme levels could serve as an indicator of pulmonary injury induced by generic coal dusts when compared to known fibrogenic and nuisance dusts. Installation of generic quartz, anthracite, or TiO2 dusts produced significant elevations of enzyme activity and increased numbers of macrophages in the dust-exposed lobes. Elevations in enzymatic activity and macrophage numbers were greatest in response to generic quartz dust. These results suggest that quantitative levels of N-acetyl-beta-D-glucosaminidase activity may be a useful indicator of acute and chronic lung injury following exposure to fibrogenic and nonfibrogenic dusts. PMID- 7776703 TI - Pulmonary neuroepithelial bodies in neonatal and adult dogs: histochemistry, ultrastructure, and effects of unilateral hilar lung denervation. AB - In neonatal dogs, neuroepithelial bodies (NEB) are located in the distal lung. They consist of closely packed and granulated epithelial cells showing a positive immune reaction to serotonin and carrying well-developed apical microvilli. They make close contact with capillaries and form morphologically afferent synaptic junctions with intracorpuscular nerve endings. Since most nerve endings degenerate after hilar lung denervation, they are carried by extrinsic, most likely vagal, sensory nerve fibers. We conclude that pulmonary NEB probably are receptor organs, sampling the inspired air and secreting bioactive substances. These might have a local vaso- or bronchoactive regulatory effect, or could be carried to other body parts via the blood vessels. In addition, NEB might induce integrative reflexes via the central nervous system. The NEB intracorpuscular nerve endings also show spontaneous degeneration. This, in addition to the scarcity of NEB in the distal lungs of adult dogs, strongly suggests that the pulmonary NEB are particularly important during the perinatal period of life. PMID- 7776704 TI - Differential cell count and lymphocyte subsets in bronchoalveolar lavage during pneumonia with and without peripheral neutropenia. AB - One hundred immunocompromised HIV negative patients with microbiologically positive pneumonia underwent bronchoalveolar lavage (BAL) studies. Thirty cases showed peripheral neutropenia (< 1000 neutrophils/microL), 70 did not. The total cell number in BAL, the differential cell counts, and the lymphocyte subsets (CD4, CD8, CD19, CD57) were measured. Patients with pneumonia and normal or elevated peripheral neutrophils had a significantly increased total number of cells in BAL compared to patients with peripheral neutropenia (3.2 +/- 2 vs 1.3 +/- 0.6 x 10(5) cells/ml2 lavage fluid, p < 0.01). Ninety percent of the BAL differential cell counts obtained in patients exceeding 1000 neutrophils/microL showed a lymphocytic and/or neutrophilic alveolitis, whereas only 54% of patients with peripheral neutropenia displayed abnormal counts (p < 0.01). Yet the typical pattern of neutrophilic alveolitis was found more often for peripheral neutrophil counts over 1000/microL with high significance (p < 0.0001). Abnormal BAL cell patterns for neutropenic patients uniformly showed a lymphocytic alveolitis, only 10% additionally conformed with the pattern of neutrophilic alveolitis. Patients with pneumonia with and without peripheral neutropenia had similar findings in BAL lymphocyte subsets and exhibited a reduced CD4/CD8 ratio compared to controls (p < 0.05). The high susceptibility of severe neutropenic patients to pulmonary, especially fungal infections may be explained by the local lack of neutrophils. PMID- 7776705 TI - Forced midexpiratory time: reference values and the effect of cigarette smoking. AB - BACKGROUND: Forced midexpiratory time (FET25-75%), the time required to exhale from 25 to 75% of forced vital capacity (FVC), has been advocated as a relatively volume-independent measure of obstruction. Previous estimates of normal FET25-75% have not systematically studied the effect of age, height, sex, and smoking history. METHODS: We analyzed flow-volume loops from 369 normal lifetime nonsmokers and smokers, a random sample of the population of Michigan. Linear models including age and/or height were considered, with and without logarithmic transformation. RESULTS: The best models used age, or age and height, and no transformation. Age and height contributed much less to the variability of FET25 75% than to spirometric flows previously investigated. The largest r2 was found in the male smokers, with the largest contribution from age, suggesting a smoking effect. CONCLUSIONS: As age was the major contributor to the value of FET25-75% and that contribution was small, we suggest the use of simplified age-stratified reference values derived from our data. PMID- 7776706 TI - Ozone exposure suppresses epithelium-dependent relaxation in feline airway. AB - We examined the effect of exposure to ozone on the epithelium-dependent relaxation (EpDR) of bronchioles evoked by electrical field stimulation (EFS) in a feline model with hyperresponsive airways induced by exposure to ozone. Airway responsiveness was assessed by measuring the increases in total pulmonary resistance (RL) produced by aerosolized acetylcholine (ACh) in vivo. Airway responsiveness was also measured in vitro in dissected bronchiolar ring preparations. Exposure to ozone (3 ppm, 2h) significantly increased the airway responsiveness in vivo. The concentration of ACh required increasing RL to 200% of the baseline value, decreased from 1.97 mg/ml (GSEM 1.94) to 0.12 mg/ml (GSEM 1.77, p < 0.01) after exposure to ozone. EFS evoked atropine-, guanethidine-, and tetrodotoxin-resistant relaxations in the control bronchiolar rings precontracted by 5-hydroxytryptamine. Such relaxation was significantly suppressed by the mechanical denudation of epithelium, confirming that it was epithelium dependent. The amplitude of the EpDR was significantly suppressed in the animals exposed to ozone. These results suggest that EpDR is present in cats, and that its inhibition may contribute to the development of airway hyperresponsiveness. PMID- 7776708 TI - Physiotherapy and physical therapy at Mayo. PMID- 7776707 TI - Cellular and mediator profile in bronchoalveolar lavage of guinea pigs after toluene diisocyanate (TDI) exposure. AB - Toluene diisocyanate (TDI) is a volatile, highly reactive chemical widely used as a polymerizing agent in the production of polyurethane foams, lacquers, adhesives, and other items. Repeated airway exposures in the workplace to TDI may cause a concentration-dependent risk of developing chronic airway disorders. Different pathomechanisms are involved. IgE-mediated sensitization and irritative effects were clearly demonstrated in exposed subjects as well as in animals. In this study we examined the cellular and mediator composition in bronchoalveolar lavage fluid (BALF) of guinea pigs (eight in each group) exposed to TDI (10, 20, or 30 ppb) on 5 consecutive days for 2 hours each. Increased numbers of eosinophils and significantly elevated levels of LTB4 and LTC4/LTD4/LTE4 were obtained in BALF of all exposed animals when compared to nonexposed control animals. PGD2 and TXB2 remained unaltered in BALF. Stimulation of BALF cells of exposed and control animals with Ca-ionophore A23187 and arachidonic acid induced an increased generation of LTB4. Furthermore, BALF cells of the exposed animal groups generated immunoreactive LTC4/LTD4/LTE4, whereas controls did not show peptido-leukotriene formation in the presence and absence of stimuli. Our data clearly demonstrate an influx of eosinophils into the airways associated with mediator release and higher cellular responsiveness after TDI exposure. PMID- 7776709 TI - Early and late survival after surgical treatment of culture-positive active endocarditis. AB - OBJECTIVE: To describe a 30-year experience with surgically treated culture positive active endocarditis. DESIGN: We retrospectively reviewed the microbiologic, clinical, and operative findings and the survival data in 151 patients with culture-positive active endocarditis encountered between 1961 and 1991. RESULTS: The mean age of the 110 male and 41 female patients was 49.8 years. Native valve endocarditis was present in 86 patients, and prosthetic valve endocarditis (PVE) was diagnosed in 65. The aortic valve was involved in 62% of patients, the mitral valve in 25%, and both valves in 10%. The operative mortality was 26%. The most important univariate determinants of mortality were an abscess at operation (P = 0.01) and renal failure (P = 0.03). A trend toward a higher mortality with PVE and staphylococcal infection was noted. For hospital survivors, the 5- and 10-year survival was 71% and 60%, respectively. Univariate determinants of an adverse long-term survival were annular abscess (P = 0.01), renal impairment (P = 0.01), heart failure (P = 0.02), and aortic valve involvement (P = 0.05). On multivariate analysis, the most important adverse determinants of long-term survival were heart failure (P = 0.02), renal impairment (P = 0.02), and PVE (P = 0.03). Thirty patients required a subsequent reoperation; of these, seven required a second and two a third operation. The most common reason for reoperation was periprosthetic regurgitation without infection (N = 19). Four operations were performed for recurrent endocarditis. At 5 and 10 years, the risk of reoperation was 23% and 36%, respectively. CONCLUSION: Although surgical treatment of culture-positive active endocarditis is still associated with substantial mortality, the long-term outcome of hospital survivors is excellent. Subsequent reoperations for periprosthetic leak are common, but recurrent infection is uncommon. PMID- 7776710 TI - Urinary tract anomalies detected by prenatal ultrasound examination at Mayo Clinic Rochester. AB - OBJECTIVE: To determine the frequency of fetal urinary tract anomalies and to characterize the types of such abnormalities detected on ultrasonography and the outcome of affected patients during a 15-year period at our institution. DESIGN: We retrospectively reviewed the findings on maternal prenatal ultrasound examinations and the postnatal medical records of 56 children with urinary tract abnormalities detected by prenatal ultrasound examination at Mayo Clinic Rochester from November 1979 to June 1994. RESULTS: Of the 56 children, 18 (32%) had severe urinary tract anomalies in conjunction with oligohydramnios, pulmonary hypoplasia, and perinatal death (Potter's syndrome). The other 38 infants had various urinary tract abnormalities--most commonly, isolated hydronephrosis and multicystic dysplasia of the kidney. Six of the 38 children had more than one renal abnormality detected prenatally. Reflux was noted in association with prenatally detected urinary tract abnormalities in 4 of 32 newborns (12%) who underwent voiding cystourethrography. In fetuses with normal amniotic fluid volume, the perinatal outcome was good. Children with lower urinary tract obstruction had evidence of more severe renal dysfunction than did those with involvement at more proximal levels. The presence or absence of urinary tract obstruction postnatally could not be determined reliably on the basis of prenatal ultrasound appearance. CONCLUSION: In this study, more than half of all prenatally detected urinary tract abnormalities were isolated hydronephrosis or multicystic dysplasia of the kidney. Postnatal renal function could not be reliably predicted on the basis of prenatal ultrasound findings. PMID- 7776711 TI - Treatment of stable chronic demyelinating polyneuropathy with 3,4 diaminopyridine. AB - OBJECTIVE: To determine whether 3,4-diaminopyridine (3,4-DAP) would improve clinical or electrophysiologic function in patients with stable chronic demyelinating polyneuropathy. DESIGN: We conducted a prospective, randomized, placebo-controlled, blinded, crossover study of 3,4-DAP in 34 patients with demyelinating polyneuropathy. MATERIAL AND METHODS: Of the 17 men and 17 women, who were 21 to 80 years of age, 27 had hereditary motor and sensory neuropathy type I and 7 had acquired demyelinating polyneuropathy. Treatment consisted of stepped doses of 3,4-DAP (increasing to 20 mg four times daily) or placebo for 4 days. Pretreatment and posttreatment determination of the Neurologic Disability Score (NDS); isometric muscle strength testing; median, ulnar, and peroneal nerve conduction studies; and measurement of serum 3,4-DAP were performed. Quantitative computer-assisted sensory examinations were done in five patients. RESULTS: The results for the final day of treatment with 3,4-DAP or placebo and the differences between pretreatment and posttreatment findings for total NDS, sensory NDS, isometric muscle strength testing, compound muscle action potential amplitude, sensory nerve action potential amplitude, motor and sensory conduction velocities, and vibration and cold detection thresholds did not vary significantly. A small improvement of 4 points in the motor NDS (P < 0.05) was found. Five patients with electrophysiologic conduction block had no significant reduction in the degree of block. CONCLUSION: Because no improvement was noted in most measurements of neurologic function, despite use of high doses of drug, 3,4 DAP is unlikely to be beneficial in the treatment of stable chronic demyelinating polyneuropathy. PMID- 7776712 TI - Hamilton Smith--Nobel Prize winner in medicine or physiology. PMID- 7776713 TI - Right ventricular dysplasia: the Mayo Clinic experience. AB - OBJECTIVE: To determine the initial clinical manifestations and echocardiographic features of right ventricular dysplasia as encountered in a major cardiovascular referral center in the United States. DESIGN: We conducted a retrospective study of cases of right ventricular dysplasia diagnosed at the Mayo Clinic between January 1978 and January 1993. MATERIAL AND METHODS: In an institutional data base search, we identified 20 patients with right ventricular dysplasia. Echocardiographic, electrophysiologic, Holter monitoring, cardiac catheterization, and endomyocardial biopsy results were analyzed. The mean duration of follow-up was 7 years. RESULTS: In the 12 female and 8 male patients (mean age, 30 years; range, 3 to 60), the initial manifestations of right ventricular dysplasia included ventricular arrhythmia (45%), congestive heart failure (25%), heart murmur (10%), asymptomatic (10%), complete heart block (5%), and sudden death (5%). First-order relatives were affected in 30% of the patients. Ventricular tachycardia with morphologic features of left bundle branch block was inducible in seven of nine patients. On Holter monitoring, all but 2 of 15 patients studied had frequent ventricular ectopic activity (Lown grade 2 or more). Characteristic fatty infiltration of the myocardium was present in 7 of 13 right ventricular biopsy specimens. Inordinate right ventricular enlargement was present in 60% of the patients at first echocardiographic assessment and in two other patients on follow-up assessment. Variable left ventricular involvement was noted in 50% of the cases. During the follow-up period, four patients died: two died suddenly, one died of congestive heart failure, and one died of respiratory failure after a coronary artery bypass operation. Of the 16 living patients, 8 are doing well, 3 have an implanted cardiac defibrillator, 3 are receiving antiarrhythmic agents, and 2 have undergone cardiac transplantation because of progressive biventricular failure. CONCLUSION: Patients with right ventricular dysplasia have varied initial manifestations and a high frequency of serious cardiovascular symptoms and complications. PMID- 7776714 TI - Medical coverage for multievent sports competition: a comprehensive analysis of injuries in the 1994 Star of the North Summer Games. AB - OBJECTIVE: To determine the incidence and type of requests for medical assistance and the treatment required in 21 sports at the 1994 Star of the North Summer Games and to develop a plan, based on these findings, for efficient allocation of medical supplies and staff. DESIGN: We reviewed our experience with a large multisport amateur athletic event and analyzed the pattern of injuries for participants in the various sports. MATERIAL AND METHODS: Injury evaluation forms and medical supply kits were given to the health-care volunteers, who received preliminary instructions on classifications and definitions of injuries and on appropriate completion of the forms. When a medical contact occurred, an evaluation form was completed. The data from these forms were subsequently compiled and analyzed. RESULTS: Of 6,243 athletes who participated in the 1994 Star of the North Summer Games, 55 (0.88%) received medical attention (2 officials also required medical assistance). The sports with the greatest number of medical contacts were soccer and track and field--31 and 16 contacts for medical assistance, respectively. The lower extremities were the anatomic site most frequently involved in injury (62% of the medical contacts). The most common types of injury were contusions, strains, and sprains. CONCLUSION: Because few injuries were sustained and most were of minor severity, basic medical supplies (such as ice bags and compression wraps) were sufficient. For locations with a scarcity of medical personnel, a triage system can be established in which athletic trainers or registered nurses manage the initial assessments and refer cases, as needed, to physicians for specialized care. An effective communication system can also considerably reduce volunteer hours. PMID- 7776715 TI - Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. AB - OBJECTIVE: To evaluate the effects of nicotinic acid on serum thyroid hormone levels in the absence of systemic illness or hepatic dysfunction. DESIGN: We determined the effect of treatment with nicotinic acid on serum thyroid hormone levels in one female and four male patients (mean age, 44.4 years) with hyperlipidemia. MATERIAL AND METHODS: In the five study patients, we measured serum lipids in conjunction with serum thyroxine (T4), triiodothyronine (T3) resin uptake, T3, free T4, thyroid-stimulating hormone (TSH), and thyroxine binding globulin before, during, and after treatment with nicotinic acid. RESULTS: Serum lipid levels responded appropriately to nicotinic acid treatment. Thyroid function studies done a mean of 1.3 years (range, 0.5 to 3.5) after initiation of nicotinic acid therapy (mean daily dose, 2.6 +/- 0.7 g) revealed significant decreases in serum levels of total T4 (21%), free T4 index (16%), T3 (13%), and thyroxine-binding globulin (23%) (P < 0.02), whereas no significant changes were noted in free T4, T3 resin uptake, and TSH levels. During the course of treatment, the patients, who were carefully questioned, had no symptoms of hypothyroidism. Hypothyroidism was further excluded in three patients who had a normal serum TSH response to administration of thyrotropin-releasing hormone. In two patients, measurements of thyroid function returned to pretreatment levels after discontinuation of nicotinic acid therapy. No patient had significant abnormalities in liver-associated enzymes or evidence of systemic illness during the course of treatment. CONCLUSION: These results suggest that nicotinic acid decreases serum thyroid hormone concentrations while maintaining a euthyroid state. This effect may be mediated through reduction in thyroxine-binding globulin, but other mechanisms may also be involved. PMID- 7776717 TI - Rheumatoid vasculitis manifesting as intra-abdominal hemorrhage. AB - Rheumatoid vasculitis, an extra-articular component of rheumatoid arthritis, causes a wide spectrum of manifestations that range from clinically insignificant to life-threatening disease. As a systemic necrotizing arteritis, rheumatoid vasculitis is usually characterized by end-organ ischemia. Herein we describe a patient with abdominal pain and syncope due to intra-abdominal hemorrhage from a ruptured aneurysm of the inferior pancreaticoduodenal artery in the setting of rheumatoid vasculitis. Although the intra-abdominal hemorrhage was the unusual manifestation of rheumatoid vasculitis in this patient, he had a history of prior extra-articular rheumatoid disease, including pulmonary fibrosis and Sjogren's syndrome with associated parotid lymphoproliferative disease. In patients with rheumatoid arthritis who have abdominal pain and an unexplained rapidly decreasing hemoglobin concentration, the diagnosis of intra-abdominal hemorrhage from a ruptured visceral aneurysm due to rheumatoid vasculitis should be considered, even in the absence of other indications of systemic vasculitis. PMID- 7776716 TI - Chronic hepatitis C and skin diseases: a review. AB - OBJECTIVE: To emphasize the ongoing role of chronic hepatitis C virus (HCV) infection in the cause or exacerbation of severe dermatologic disorders. DESIGN: We present two case reports to outline the pertinent findings in hepatitis C related cryoglobulinemia, leukocytoclastic vasculitis, and lichen planus and discuss the main disorders associated with chronic HCV infection. RESULTS: Chronic HCV infection has recently been recognized in association with various skin disorders. The most commonly reported association is the triad of leukocytoclastic vasculitis, cryoglobulinemia, and chronic HCV infection. Other cutaneous disorders associated with HCV infection include porphyria cutanea tarda, lichen planus, erythema nodosum, urticaria, erythema multiforme, and polyarteritis nodosa. CONCLUSION: Patients with onset or exacerbation of these disorders should undergo assessment for HCV infection. PMID- 7776718 TI - Schnitzler's syndrome: two case reports and review of the literature. AB - Schnitzler's syndrome is a combination of chronic urticaria, fever of unknown origin, disabling bone pain, hyperostosis, increased erythrocyte sedimentation rate, and macroglobulinemia. Since it was first described in 1974, only 26 cases have been published in the literature. In this report, we describe two additional cases and review the clinical features and pathogenesis of this uncommon syndrome. PMID- 7776719 TI - Commonly asked questions about thyroid function. AB - Thyroid function abnormalities in asymptomatic outpatients are common. When a patient is found to have an abnormality in thyrotropin (thyroid-stimulating hormone) or free or total thyroxine (T4), a review of the patient's medications and a careful neck examination will usually provide the explanation. Further diagnostic laboratory studies should include additional tests of T4 or thyrotropin. Determining the presence of antimicrosomal antibodies is useful for further assessment of "subclinical" hypothyroidism, and measures of protein binding (T4-binding capacity or T4-binding protein electrophoresis) help confirm a suspected congenital or acquired abnormality of T4 binding. Recognition of euthyroid hypothyroxinemia and hyperthyroxinemia is important in order to avoid intervention with inappropriate treatment. Management of subclinical hypothyroidism and hyperthyroidism necessitates clinical judgment about the patient's symptom profile and risks for long-standing or progressive thyroid dysfunction. PMID- 7776720 TI - Transcutaneous drug delivery: a practical review. AB - OBJECTIVE: To describe the advantages, disadvantages, practical considerations, and future developments of transcutaneous drug delivery. MATERIALS AND METHODS: The physiochemical properties of the drug preparation that are factors in the effectiveness of transcutaneous transport are drug stability or volatility, use of a solvent carrier or vehicle, use of a penetration enhancer, and type of delivery device. Because a drug should remain on the skin without evaporating or becoming otherwise inactive, it is suspended in a vehicle--any gel, lotion, or paste used to apply the drug to the skin. Penetration enhancers include several compounds that are mixed into vehicles to alter the molecular environment of the epidermis and facilitate absorption. The delivery system itself occasionally proves to be the ultimate determinant of transdermal drug flow. RESULTS: The advantages of transcutaneous drug delivery are avoidance of the gastrointestinal tract and hepatic first-pass biotransformation and metabolism, control of absorption, availability of multiple skin sites to avoid local irritation and toxicity, and improved patient compliance. The disadvantages include the potential for localized irritant and allergic cutaneous reactions, systemic toxicity, and difficulties associated with the time necessary for a drug to diffuse through the skin. CONCLUSION: Transdermal drug regimens are safe and effective. They provide clinicians the opportunity to offer more therapeutic options to their patients to optimize their care. PMID- 7776722 TI - New directions for pulse oximetry in sleep disorders. PMID- 7776721 TI - 39-Year-old man with fever, cough, and dyspnea. PMID- 7776723 TI - Assisted suicide and the savings clause. AB - In December 1994, the Michigan Supreme Court decided a group of cases comprising constitutional challenges to a Michigan statute against assisted suicide and prosecutions of Dr. Jack Kevorkian for his role in two incidents of suicide. The court rejected arguments that the statute infringed a right of "personal autonomy" under the Fourteenth Amendment to the US Constitution; it noted that, although US Supreme Court opinions indicate that decisions to withdraw or reject life-sustaining treatment are constitutionally protected, a legal difference exists between permitting death to occur by natural means and taking affirmative steps to end life. The Michigan court also decided that Kevorkian could not be charged with murder for supplying only the means by which suicide occurred, but he could be charged with a common law crime of assisting in suicide although the statute outlawing such actions became effective only after the suicides occurred. Because suicide was a crime under the prerevolutionary English Common Law, which forms the foundation of Michigan law, assisting in suicide is also a residual crime under the "savings clause" of the Michigan statutes, which incorporates common law crimes into the law of that state when no superseding statute exists. PMID- 7776724 TI - Ventilator care beyond the intensive-care unit. PMID- 7776725 TI - Surgical therapy for infective endocarditis. PMID- 7776728 TI - Kveim test. PMID- 7776727 TI - Management of fetal hydronephrosis. PMID- 7776726 TI - Fetal hydronephrosis. PMID- 7776729 TI - Technology and enlightenment philosophy. PMID- 7776730 TI - [Is medical care adequate in cases of the common cold? The result of an evaluation in 8 health centers]. AB - BACKGROUND: In this study the quality of health care provided in cases of the common cold and similar was studied. These diseases were selected to seek opportunities for improvement for health care professionals by the nominal group technique. METHODS: A retrospective study of the health care procedures was carried out in randomized sample of cases attended in one month in eight health care centers randomly selected from among the centers in the Autonomic Community of Murcia. A total of 400 cases (50 per center) were studied with the variability among centers with regard to the fulfillment of consensus criteria (physical examination, treatment registration, and appropriate prescription) and the relationship with certain characteristics of the center (university, urban) and the health care staff (general physicians, or pediatricians) being analyzed. RESULTS: Great variability was found from one center to another regarding the criteria of physical examination and prescription, the simultaneous low fulfillment of the three criteria of quality (from 2 to 60%), the positive association between physical examination and the correct prescription (p < 0.01) and a higher level of quality in urban centers (OR: 7.5, p < 0.00001). Antibiotics were prescribed in 89% (CI 95%: +/- 4.6) of the cases with inappropriate prescription in 47% of the total (CI 95%: +/- 4.9; range among centers: from 4.1 to 75.7%). CONCLUSIONS: The quality of health care towards the common cold may be markedly improved in most of the centers studied. The frequency of the use of antibiotics and the lack of physical examination are the basis of problematic and ineffective performance, being more frequently observed in rural and semirural centers. PMID- 7776731 TI - [Energy balance and caloric profile in the elderly obese or in those with overweight compared to those of normal weight]. AB - BACKGROUND: Elderly obese people have higher morbidity and mortality rates than those of normal weight and thus deeper knowledge of the problem of obesity is required in order to establish measures for prevention and correction. The aim of this study was to analyze the differences in the energetic ingestion and caloric profile in the diets of elderly patients based on their body mass index (BMI). METHODS: A collective of 127 elderly patients (44 institutionalized and 83 not) from 65 to 89 years of age were studied being grouped as: overweight-obese elderly (BMI > 25 kg/m2) and normal weight elderly patients (BMI < 25 kg/m2). The ingestion of energy and caloric profile of their diets was calculated in both groups by the "precise individual weight" method (in the institutionalized patients) and by the "register of food consumption" (in non institutionalized patients). The data of energetic ingestion were validated by comparison with the energy spent calculated on the basis of weight, age, and the daily activities of each patient. RESULTS: No significant differences were found between the energetic ingestion of overweight and obese elderly persons and those of normal weight, although the former had a more unbalanced caloric profile, with greater protein contribution and lesser carbohydrate contribution to total calories. It was also found that overweight and obese elderly patients underevaluate their energetic ingestion more than those of normal weight. CONCLUSIONS: The main difference observed between overweight-obese elderly patients with respect to those of normal weight was in the composition of their diets more than in the total energetic consumption. PMID- 7776732 TI - [The quantification of human immunodeficiency virus viremia in patients with rapid and slow progression of the disease]. AB - BACKGROUND: The natural course of the human immunodeficiency virus type 1 (HIV-1) infection is very variable. The factors which appear to determine the speed of immunodeficiency progression are multiple, although the virulence of the predominant viral strain seems to be one the main factors. The plasmatic viremia in individuals with rapid and slow HIV-1 progression was analyzed in an attempt to establish the degree of correlation between HIV-1 replication and the natural course of the disease. METHODS: Forty-two samples from 34 seropositive patients, 11 with rapid progression criteria (< 5 years from acute infection and CD4+ lymphocytes < 0.2 x 10(9)/l) and 23 with slow progression (> 7 years from demonstrated infection and > 0.5 x 10(9) CD4+ lymphocytes/l) were studied. The plasmatic viremia was quantified by a new method of plasma DNA genetic amplification, denominated the branched DNA (bDNA) technique. As a reference circulating p24 was determined and the presence of several proviral regions were studied in peripheral blood lymphocytes by polymerase chain reaction (PCR). RESULTS: The presence of RNA molecules was detected in plasma of 7 (58.3%) out of 12 samples of rapid progression (RP) patients by bDNA. To the contrary, this was negative in 30 samples from slow progression (SP) patients. Four of the 5 negative RP samples corresponded to patients who had taken antiretroviral drugs at the time of the study. The p24 antigenemia was positive in 5 (41.6%) from the RP patients and in none of the SP patients. The presence of gag, pol and env sequences was positive by PCR in all RP patients and in most of the SP patients. However, repeatedly negative results by PCR were observed in 5 SP samples for all or some of the genomic regions studied. CONCLUSIONS: Patients with rapid progression of HIV-1 have higher plasmatic viremia than subjects with slow disease progression. PMID- 7776733 TI - [Do we know how to treat the common cold?]. PMID- 7776734 TI - [The quality of medical care]. PMID- 7776735 TI - [Oligoamnios associated with the use of magnesium dipyrone]. AB - Oligohydramnios induced by indomethacin has been documented both clinically and experimentally. The same is not true for all the drugs inhibiting the synthesis of prostaglandins. The case of a full term pregnant woman diagnosed with renal cholic and treated with high doses of magnesium dipyrone who developed echographically diagnosed oligohydramnios at 60 h of initiation of the treatment is presented. Delivery was induced by the double intracervical application of 0.5 mg of prostaglandin E2 over an interval of 24 h. At 35 h of the discontinuation of magnesium dipyrone the patient was echographically reevaluated with the volume of the amniotic fluid being found to be normal. Although no reports have been found concerning oligohydramnios by magnesium dipyrone, the negative effect of this drug on urine flow in healthy individuals is known. In the absence of other hypotheses, the authors suggest that the use of high doses of this drug may significantly reduce fetal urine flow and be responsible for a drastic reduction in amniotic fluid. The adverse effect was determined as possible by evaluation of secondary effects by Naranjo's algorithm. PMID- 7776736 TI - [Alcohol consumption indicators in Spain]. PMID- 7776737 TI - [Stress and cardiovascular problems]. PMID- 7776738 TI - [Myoclonia and psoriasiform syphilids in a case of late syphilis]. PMID- 7776739 TI - [CD4+ lymphocytes in patients with a Leishmania-HIV coinfection]. PMID- 7776741 TI - [The characteristics of food poisoning due to clenbuterol]. PMID- 7776740 TI - [Cholestatic jaundice, an infrequent initial manifestation of primary amyloidosis]. PMID- 7776742 TI - [A cerebral infarct associated with a giant cerebral arteriovenous malformation]. PMID- 7776743 TI - [A pancreatic abscess due to Candida albicans]. PMID- 7776744 TI - [Anaphylactic shock following the ingestion of a laxative]. PMID- 7776745 TI - [Neologic smoke screens conceal depersonalization. What does "prioritization committees" mean?]. PMID- 7776746 TI - [Tissue expansion--a sufficient factual basis is missing]. PMID- 7776747 TI - ["Hjartsvikt" ("heart swing")--a mined field or virgin soil?]. PMID- 7776748 TI - [Inter-professional ethics]. PMID- 7776749 TI - [The first step towards a patient-originated medical record?]. PMID- 7776750 TI - [Antibiotics against appendicitis. A promising alternative to surgery?]. PMID- 7776751 TI - [Pollen registration--a social problem. Continuing increase of allergies]. PMID- 7776753 TI - [27,800 visitors at the annual meeting of the Swedish Medical Society 1994]. PMID- 7776752 TI - [Group living for individuals with chronic psychiatric disorders.A form of independent care that increases quality of life]. PMID- 7776754 TI - [Nerve growth factors in future therapies. Protein mutation broadens the range of therapeutic possibilities]. AB - The development and maintenance of the vertebrate nervous system requires a continuous supply of a number of polypeptide hormones known as neurotrophic factors. The ability of neurotrophic factors to promote the survival of peripheral and central neurons during development and after neuronal damage has aroused interest in these molecules as potential therapeutic agents for the treatment of nervous lesions and neurodegenerative diseases. Understanding of the molecular basis of the biological specificity of neurotrophic polypeptides has provided insight into their mechanisms of action and allowed strategies to be developed for the rational design of derivatives and analogues with specific pharmacological properties. PMID- 7776756 TI - [A new way of dealing with malpractice in the USA? Jail for physicians after medical mistakes]. PMID- 7776755 TI - [Risk of overdiagnosis of urine cultures]. PMID- 7776757 TI - [Estrogen treatment caused acute attacks of porphyria]. AB - Two female patients with acute intermittent porphyria, who received oestrogen skin pads as supplementary treatment for postmenopausal discomfort, developed severe psychiatric disorders with persistent confusion, aggression and paranoid reactions. Some decades earlier they had reacted with symptoms of acute porphyria following oral contraceptive usage. There is well documented evidence of the advisability of restrictiveness in the use of oestrogens in conjunction with acute porphyria, particularly in cases of patients with a history of hormone related symptoms of acute porphyria. The putative mechanisms by means of which oestrogens may exert effects on neurotransmitters and peptides are discussed in the article. The authors would be grateful to hear from colleagues abroad who have treated patients with similar symptoms following postmenopausal treatment with oestrogens. PMID- 7776759 TI - [Evaluation of process economics is not a sufficient basis for decision on health policy]. PMID- 7776758 TI - [Changed treatment of schizophrenic syndromes. More open care is not cheaper]. PMID- 7776760 TI - [From what--to what? Reflections on terminal care]. PMID- 7776761 TI - [New traumatology education will be introduced in Sweden in 1996]. PMID- 7776762 TI - [Recommendations on treatment of peripheral mycoses. The importance of diagnosis prior to treatment]. PMID- 7776763 TI - [No proof that hypersensitivity can be caused by electromagnetic fields. Patient's experience must be respected!]. PMID- 7776764 TI - [It is not enough to be kind. Many physicians lack professional assurance]. PMID- 7776765 TI - Humanitarian olympics: Solferino to Goma. PMID- 7776766 TI - Cryptococcosis, AIDS, and clinical trials. PMID- 7776768 TI - Birth of the midwife/obstetrician. PMID- 7776767 TI - Women as women with HIV. PMID- 7776769 TI - Interactions with selective MAOIs. PMID- 7776770 TI - Mental disorders and disability across cultures: a view from South Africa. PMID- 7776771 TI - Continuing increase in mesothelioma mortality in Britain. AB - Mesothelioma is closely related to exposure to asbestos, and mesothelioma mortality can be taken as an index of past exposure to asbestos in the population. We analysed mesothelioma mortality since 1968 to assess the current state of the mesothelioma epidemic, and to predict its future course. We found that rates of mesothelioma in men formed a clear pattern defined by age and date of birth. Rates rose steeply with age showing a very similar pattern in all five year birth cohorts. By date of birth, rates increased from mid-1893 to mid-1948, and then fell. Relative to the 1943-48 cohort, the risk for the 1948-53 cohort is 0.79 and for the 1953-58 cohort 0.48. Despite these falls, if the age profile of rates for these cohorts follows the pattern of past cohorts, their predicted lifetime mesothelioma risks will be 1.3%, 1.0%, and 0.6%. Combining projections for all cohorts results in a peak of annual male mesothelioma deaths in about the year 2020 of between 2700 and 3300 deaths. If diagnostic trend is responsible for a 20% growth in recorded cases every 5 years--an extreme but arguable case--and if this trend has now ceased, the peak of annual male deaths will be reduced to 1300, reached around the year 2010. Analysis of occupations recorded on death certificates indicate that building workers, especially plumbers and gas fitters, carpenters and electricians are the largest high-risk group. These data indicate that mesothelioma deaths will continue to increase for at least 15 and more likely 25 years. For the worst affected cohorts--men born in the 1940s- mesothelioma may account for around 1% of all deaths. Asbestos exposure at work in construction and building maintenance will account for a large proportion of these deaths, and it is important that such workers should be aware of the risks and take appropriate precautions. PMID- 7776772 TI - Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology. AB - The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential. PMID- 7776773 TI - Aminophylline for methotrexate-induced neurotoxicity. AB - Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5 hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a 1-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline. PMID- 7776776 TI - Cardiac chamber-specific beta-adrenoceptor regulation and sympathetic innervation. AB - We assessed by radioligand binding techniques the effect of cardiac failure on beta-adrenoceptor density in 5 hearts from patients undergoing repeat transplantation and 5 normal (unused donor) hearts. Right ventricular total and subtype beta-adrenoceptors in the denervated repeat-transplant hearts were down regulated compared with the normally innervated controls. Within the denervated hearts, beta 1-adrenoceptors were selectively down-regulated in the right ventricle compared with the left ventricle. Tissue noradrenaline content confirmed sympathetic denervation in the transplanted hearts. Thus, regional sympathetic innervation is not necessary for chamber-specific beta-adrenoceptor down-regulation; other mechanisms for this process should be sought. PMID- 7776774 TI - Primary prevention of cryptococcal meningitis by fluconazole in HIV-infected patients. AB - To evaluate whether oral fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV-infected patients, we conducted a case-control study of patients cared for in a university teaching hospital and two urban HIV outpatient clinics. Cases consisted of HIV-infected patients with CD4 cell counts less than 250/microL who developed a first episode of cryptococcal meningitis between July 1, 1990, and June 30, 1993. For each case (n = 18), 4 control subjects were chosen from HIV-infected patients (CD4 count < 250/microL) whose cerebrospinal fluid was negative for cryptococcal antigen and culture, and who were matched by age, sex, and time of lumbar puncture. There were no significant differences between cases and controls in age, sex, insurance status, mean CD4 count, history of oral candidosis, presence of a previous AIDS-defining illness, the number of visits to the HIV-outpatient clinic, or use of antiretroviral therapy. In the 6 months before lumbar puncture, 2 of 18 cases (11%) and 26 of 72 controls (36%) were exposed to fluconazole, a finding that gives a matched odds ratio (adjusted for race, route of HIV infection, and CD4 count) of 0.08 (95% CI 0.01-0.84; p = 0.035) and indicates a 92% protective efficacy. We conclude that fluconazole reduces the risk of a first episode of cryptococcal meningitis in HIV infected patients with a CD4 count less than 250/microL. Although the optimum dose and duration of fluconazole could not be determined, our results suggest that less than daily use was effective in the prevention of cryptococcal meningitis. PMID- 7776777 TI - Genetic diversity of hepatitis C virus: implications for pathogenesis, treatment, and prevention. Report of a meeting of Physicians and Scientists. PMID- 7776775 TI - Alpha-ketoglutarate for myocardial protection in heart surgery. AB - A low myocardial content of alpha-ketoglutarate during heart surgery might aggravate ischaemic injury. 24 men undergoing coronary surgery participated in a randomised controlled study. 28 g alpha-ketoglutarate was added to blood cardioplegia for intermittent antegrade intracoronary perfusion in 13 cases. alpha-ketoglutarate reduced the appearance in blood of the ischaemic markers creatine kinase MB and troponin T (at 4 h after release of aortic cross-clamp; median [95% CI] 49 [37-60] micrograms/L in controls vs 32 [27-37] micrograms/L for creatine kinase MB, 2.0 [1.2-2.8] vs 1.1 [0.8-1.4] micrograms/L for troponin T). These findings signify attenuated ischaemic injury, possibly secondary to enhanced myocardial oxidative capacity. PMID- 7776778 TI - Alarm over supervised discharge orders. PMID- 7776779 TI - Abolition of year-and-a-day rule in homicide recommended. PMID- 7776780 TI - Superspecialists and the Bolam test. PMID- 7776781 TI - Spotlight on inhibitors of HIV protease. PMID- 7776782 TI - Crisis in humanitarian action assessed. PMID- 7776783 TI - Trials of streptokinase in severe acute ischaemic stroke. PMID- 7776784 TI - Trials of streptokinase in severe acute ischaemic stroke. PMID- 7776786 TI - Does interferon beta cause initial exacerbation of multiple sclerosis? PMID- 7776785 TI - Nabilone in the treatment of multiple sclerosis. PMID- 7776787 TI - Oral rehydration solution as adjuvant for oral vaccination. PMID- 7776788 TI - Galactosaemia. PMID- 7776789 TI - Frequency of familial melanoma and MLM2 gene. PMID- 7776790 TI - Frequency of familial melanoma and MLM2 gene. PMID- 7776791 TI - Treatment of Indian kala-azar with pentavalent antimony. PMID- 7776792 TI - When to use fluconazole. PMID- 7776793 TI - Treatment of Indian Kala-azar with pentavalent antimony. PMID- 7776795 TI - Hormone replacement therapy and cardiovascular risk. PMID- 7776794 TI - Intestinal mycobacteria in African AIDS patients. PMID- 7776796 TI - Treatment of late Lyme borreliosis with cefoperazone and sulbactam. PMID- 7776797 TI - Abortion. PMID- 7776798 TI - Abortion. PMID- 7776800 TI - Abortion. PMID- 7776799 TI - Abortion. PMID- 7776801 TI - Is it possible to have an unconscious thought? PMID- 7776802 TI - Indirect drug-related costs. PMID- 7776803 TI - Essence of stress. PMID- 7776804 TI - Treatment of chlamydial infection in developing countries. PMID- 7776805 TI - Prenatal diagnosis in congenital muscular dystrophy. PMID- 7776806 TI - Cholesterol-lowering, simvastatin, and coronary heart disease. PMID- 7776807 TI - Laparoscopic hysterectomy. PMID- 7776808 TI - Laparoscopic hysterectomy. PMID- 7776809 TI - Laparoscopic hysterectomy. PMID- 7776810 TI - Laparoscopic hysterectomy. PMID- 7776811 TI - Enterococci and hospital laundry. PMID- 7776812 TI - Proteinase-resistant protein in human neuroblastoma cells infected with brain material from Creutzfeldt-Jakob patient. PMID- 7776813 TI - Apolipoprotein E in Creutzfeldt-Jakob disease. French Research Group on Epidemiology of Human Spongiform Encephalopathies. PMID- 7776815 TI - International Symposium on Cannabis and the Cannabinoids. Proceedings. Esterel, Quebec, Canada. July 21-23, 1994. PMID- 7776814 TI - Proctoclysis for hydration. PMID- 7776816 TI - A review of recent advances in cannabinoid research and the 1994 International Symposium on Cannabis and the Cannabinoids. PMID- 7776817 TI - Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist. AB - SR141716A is a selective, potent and orally active antagonist of the brain cannabinoid receptor with a long duration of action. This compound shows high affinity for the central cannabinoid receptor (Ki = 2 nM), displays low affinity for the peripheral cannabinoid receptor (Ki > 1000 nM). In vitro, SR141716A antagonizes the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and dopamine-stimulated adenylyl cyclase activities in rat brain membranes. After oral administration SR141716A totally inhibited the ex vivo [3H]-CP55,940 binding to cerebral membranes with a ED50 value of 3.5 mg/kg. Furthermore SR141716A antagonizes the classical pharmacological responses elicited by cannabinoid receptor agonists. In addition, SR141716A reverses the inhibitory effect of WIN55212-2 on isoniazid-induced elevation of cGMP in rat cerebellum. This compound will provide a powerful tool for studying the in vivo functions of the anandamide/cannabinoid system. PMID- 7776818 TI - AM630, a competitive cannabinoid receptor antagonist. AB - AM630 (iodopravadoline), a novel aminoalkylindole, has been found to attenuate the ability of a number of cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens. It did not block the inhibitory effects of morphine or clonidine on the twitch response. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1' hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists that were concentration-dependent, essentially parallel and not accompanied by any decrease in the size of maximal response. AM630 also produced concentration-dependent, parallel rightward shifts in the log concentration-response curve of delta 9-THC. However, these shifts were accompanied by a decrease in the maximal response. AM630 was markedly more potent as an antagonist of delta 9-THC and CP 55,940 (Kd = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (Kd = 36.5, 85.9 and 278.8 nM respectively). These differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor. The data also indicate that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors as the CB1 selective antagonist, SR141716A, is known to be equally potent in attenuating the inhibitory effects of CP 55,940 and anandamide on the twitch response of the mouse vas deferens. PMID- 7776819 TI - A novel electrophilic high affinity irreversible probe for the cannabinoid receptor. AB - In order to explore the structural requirements for cannabinoid activity we have been involved in the design and synthesis of stereochemically defined high affinity probes for the cannabinoid receptor. This effort has involved the development of irreversible ligands which will allow us to obtain detailed information on the cannabinoid receptor active site(s). The irreversible ligands, which incorporate highly reactive functional groups in a strategic position of the ligand, may form covalent bonds with amino acid residues at the receptor active site or in the neighborhood of this site. We shall discuss the biochemical properties of one of these probes, which incorporates the electrophilic isothiocyanate group into the structure of the highly potent cannabinoid agonist (-)-1',1'-dimethylheptyl-delta 8-THC. This ligand, (-)-7'-isothiocyanato-1',1' dimethylheptyl-delta 8-THC (7'-NCS-DMH-delta 8-THC), was evaluated for its affinity for cannabinoid binding sites using rat forebrain membrane preparations and found to have an apparent IC50 value of 660 pM. Incubation of the membrane preparation with a ligand concentration of five times the apparent IC50 resulted in the irreversible occupation of nearly all of the receptor specific binding sites. PMID- 7776820 TI - Common cannabimimetic pharmacophoric requirements between aminoalkyl indoles and classical cannabinoids. AB - Aminoalkylindoles (AAIs) are structurally dissimilar from the classical cannabinoids (CCs), however, both AAIs and CCs appear to bind at the same site on the cannabinoid receptor. To obtain better insights on the structural correlation between AAIs and CCs, we have studied the conformational properties of the potent cannabimimetic AAI WIN 55212-2 and its inactive analogs using high resolution 2D NMR spectroscopy in combination with computer-assisted molecular modeling. The pharmacophoric similarities between the AAIs and the CCs were then investigated using superimposition techniques. The absolute stereochemistries of the biologically active enantiomer (-)HHC were used as superimposition points and considered as internal controls in order to test the molecular principles guiding this experiment. Our results show that the model is congruent with a superimposition in which the naphthoyl, morpholino and 3-keto groups in the AAI, respectively correspond to the side chain, cyclohexanol OH and phenolic OH of HHC. A good fit is obtained when the two biologically active antipodes are superimposed. Conversely, the fit is poor if the inactive AAI enantiomer is superimposed on the active HHC enantiomer. It can also be seen that in such an orientation a certain deviation of the C-ring from the plane of the phenol ring of the tricyclic HHC component and of the morpholinyl portion from the plane of the indole ring of WIN 55212-2 is essential for cannabimimetic activity. The inactive enantiomer WIN 55212-3 has its respective components aligned in the opposite quadrant. By comparing the stereoelectronic features of representative AAIs and CCs, we have developed a model which may help to uncover the pharmacophoric requirements of the AAIs and serve as a basis for future SAR and drug design. PMID- 7776821 TI - Construction of a 3D model of the cannabinoid CB1 receptor: determination of helix ends and helix orientation. AB - The goal of this study was to determine the ends and orientations of the seven transmembrane helices of the cannabinoid (CB1) receptor, a G-protein coupled receptor (GPCR). After initial sequence alignment, Fourier transform methods were used with the nPRIFT hydrophobicity scale and with a variability profile to calculate the alpha-helical periodicity (AP) in the primary amino acid sequence of the human CB1 receptor and of its alignment. AP plots were used to identify the amino acids which comprise each of the seven CB1 transmembrane helices. An intracellular alpha helix extension of Helix 7 was characterized by analyzing the relative direction of variability and hydrophobic moment vectors. Variability moment vectors were then used to delineate the orientation of each helix in the membrane. Based upon these vector calculations, a tentative helix bundle arrangement was obtained. This arrangement is largely consistent with the proposed transmembrane helix bundle arrangement in rhodopsin, a GPCR. PMID- 7776822 TI - Rat brain cannabinoid receptors are N-linked glycosylated proteins. AB - To study the N-linked glycosylation properties of the CB1 receptor, rat brain membranes were treated with exo- and endoglycosidases. For visualizing CB1 receptors, an antipeptide antibody was raised against the N-terminal 14 amino acids and used to specifically detect the protein by Western blotting. We found that the apparent molecular weight of mature CB1 receptors was 64 kDa. Treatment of membranes with endoglycosidase F shifted the 64 kDa band to the 59 kDa and 53 kDa bands. The latter is consistent with the calculated molecular weight of deglycosylated CB1 receptors. Treatment of membranes with endoglycosidase H and alpha-mannosidase partially shifted the 64 kDa band to 53 kDa band, indicating a portion of the oligosaccharides was of the high mannose type. These data confirmed that the CB1 receptors in brain are N-linked glycoproteins with heterogeneous carbohydrate composition. Among three potential N-linked glycosylation sites on the N-terminus of the CB1 receptor, only two sites are actually glycosylated. PMID- 7776823 TI - Cannabinoid photolabelling of a G-protein gamma-subunit in mouse peritoneal cells. AB - Binding and photoactivation of a cannabinoid-derived ligand to intact mouse peritoneal cells has resulted in the labelling of a G-protein gamma-subunit. The assignment of structure is based on the product's physical characteristics and its ability to react with a polyclonal antiserum raised against the partial amino acid sequence for a gamma-subunit expressed in spleen cells. The binding characteristics of the ligand to the cells suggests that this gamma-subunit, and its associated alpha and beta subunits, are located in close proximity to one of the transmembrane cannabinoid receptors. Our findings further suggest a possible experimental approach to identifying receptor-G-protein complexes in intact cells. PMID- 7776824 TI - Arachidonoyl ethanolamide-[1,2-14C] as a substrate for anandamide amidase. AB - Arachidonoyl ethanolamide-[1,2-14C] was prepared and evaluated as a substrate for anandamide amidase in a radioenzymatic assay that does not require a thin layer chromatography separation step. Using this substrate the release of ethanolamine [1,2-14C] is linear for approximately thirty minutes. Anandamide amidase exhibits maximal activity between pH 8 and pH 9 with a steep decline in activity at pH values below 6 and above 10. Arachidonoyl ethanolamide-[1,2-14C] was used for the assay of anandamide amidase from 10 micrograms to 100 micrograms protein, from cow brain homogenate, in a 0.2 ml incubation mixture. When plotted as a rectangular hyperbola of the steady-state Michaelis-Menten equation, an approximate Km of 30 +/- 7 microM and a Vmax of 198 +/- 13 nmoles ethanolamine formed per hour per mg protein homogenate was obtained. PMID- 7776825 TI - Classical/non-classical cannabinoid hybrids; stereochemical requirements for the southern hydroxyalkyl chain. AB - We have synthesized a range of hybrid classical/non-classical cannabinoids (CC/NCCs) combining the hexahydrocannabinol dibenzopyran structure with the hydroxyalkyl chain found in CP-55940, in order to investigate the role of the hydroxyalkyl pharmacophore in cannabimimetic activity. This was achieved by synthesizing CC analogs in which the 6 alpha- and 6 beta-methyl groups were modified to the corresponding hydroxyethyl groups. Our binding data indicated that beta position was the preferred orientation for the hydroxyalkyl moiety, affinity for the CB1 receptor being 20-fold greater for the 6 beta-hydroxyethyl than the corresponding 6 alpha-analog. Further studies using 6 beta hydroxyalkyldibenzopyran analogs varying the southern aliphatic chain length from 6 beta-hydroxymethyl to 6 beta-hydroxyethyl to 6 beta-hydroxypropyl demonstrated little potency change with chain length. Therefore, we concluded that whilst the hydroxyalkyl pharmacophore was strongly affected by its configuration relative to the dibenzopyran ring, the chain length of the hydroxyalkyl moiety (up to the n = 3 homolog) was not critical. PMID- 7776827 TI - Variation of the alkyl side chain in delta 8-THC. AB - The synthesis of (2'RS)-2'-methyl-, (3'RS)-, (3'S)-3'-methyl-, and 4'-methyl delta 8-THC has been carried out, and the pharmacology of all four compounds has been investigated. All four compounds showed typical cannabinoid activity both in vitro and in vivo. The 2'-methyl compound is somewhat more active than delta 8 THC, while the 4'-methyl isomer is less active. The 3'-methyl-delta 8-THC has approximately the same activity as the parent cannabinoid. PMID- 7776826 TI - A novel class of potent tetrahydrocannabinols (THCS): 2'-yne-delta 8- and delta 9 THCS. AB - A series of 3-alkyl-2'-yne (side chain) acetylenic analogs of delta 9-THC were synthesized and evaluated for in vitro and in vivo activity. Analogs were evaluated for receptor affinity in a [3H]CP-55,940 displacement assay and for in vivo pharmacological activity in a mouse procedure utilizing a tetrad of measures. These compounds represent a preliminary exploration of the consequences of restricting the flexibility of the side chain regarding cannabimimetic activity. All analogs proved to have receptor affinities (4-11 nM) that were five to ten times greater than that observed for delta 9-THC. However, the in vivo activities of these compounds varied greatly. All analogs proved to possess the greatest potency for production of antinociception, with activity similar to or less than that observed for the production of hypomotility, hypothermia, and catalepsy. The most potent analog 11b exhibited an ED50 of 0.031 mg/kg in the tail-flick procedure, with values in other measures being between 0.5 and 1.0 mg/kg. The least active compound (11c), though still possessing a KI of 11 nM, exhibited ED50 values of 3.1 and 9.3 mg/kg for tail-flick and temperature procedures, as well as 41 and 48 mg/kg for ring-immobility and spontaneous locomotor activity, respectively. This profile (high receptor affinity but low in vivo potency) would normally be suggestive of a compound with antagonist properties (at least for immobility and activity measures). It is unclear why these acetylenic analogs were so potent in vitro, while only one (11b) exhibited the degree of in vivo potency anticipated based upon comparison to values for delta 9-THC. It is possible these side chain modifications do not interfere with receptor recognition, but limit receptor activation or second messenger signal transduction. Regardless, it is clear these novel analogs provide a basis for the further exploration of the cannabinoid receptor pharmacophore. PMID- 7776828 TI - The design, synthesis and testing of desoxy-CBD: further evidence for a region of steric interference at the cannabinoid receptor. AB - Cannabidiol CBD, a non-psychoactive constituent of marihuana, has been reported to possess essentially no affinity for cannabinoid CB1 receptor binding sites in the brain. Our hypothesis concerning CBD's lack of affinity for the cannabinoid CB1 receptor is that CBD is not capable of clearing a region of steric interference at the CB1 receptor and thereby not able to bind to this receptor. We have previously characterized this region of steric interference at the CB1 receptor [P.H. Reggio, A.M. Panu, S. Miles J. Med. Chem. 36, 1761-1771 (1993)] in three dimensions using the Active Analog Approach. We report here a conformational analysis of CBD which, in turn, led to the design of a new analog, desoxy-CBD. Modeling results for desoxy-CBD predict that this compound is capable of clearing the region of steric interference by expending 3.64 kcal/mol of energy in contrast to the 12.39 kcal/mol expenditure required by CBD. Desoxy-CBD was synthesized by condensation of 3-pentylphenol with p-mentha-2,8-dien-1-ol mediated by DMF-dineopental acetal. Desoxy-CBD was found to behave as a partial agonist in the mouse vas deferens assay, an assay which is reported to detect the presence of cannabinoid receptors. The compound produced a concentration related inhibition of electrically-evoked contractions of the mouse vas deferens, possessing an IC50 of 30.9 nM in this assay. Taken together, these results support the hypothesis of the existence of a region of steric interference at the CB1 receptor. While the energy expenditure to clear this region was too high for the parent compound, CBD, the removal of the C6' hydroxyl of CBD produced a molecule (desoxy-CBD) able to clear this region and produce activity, albeit at a reduced level. PMID- 7776829 TI - The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behavior: role of nigrostriatal dopaminergic neurons. AB - The present study has been designed to test whether the recently described endogenous ligand for the cannabinoid receptor, arachidonylethanolamide, termed anandamide, can mimic the effects produced by exogenous cannabinoids on motor behavior and to test possible neurochemical substrates for this potential effect. To this end, adult male rats were submitted to an acute i.p. injection of anandamide, delta 9-tetrahydrocannabinol (THC) or vehicle. Animals were behaviorally tested ten minutes after injection of the drug and, then, sacrificed and their brains used for dopaminergic analyses. Ambulation was not significantly affected by the treatment with either THC or anandamide, but a very pronounced increase was observed in the time spent in inactivity in rats treated with either THC or anandamide. This was accompanied by a marked decrease in the frequency of spontaneous non-ambulatory activities, such as grooming and rearing, although only the administration of THC decreased shaking behavior. The anandamide-induced decrease in grooming was dose-dependent, but the decrease in rearing was higher with the dose of 3 mg/kg than with the dose of 10 mg/kg. The administration of anandamide also caused a dose-dependent decrease in the activity of tyrosine hydroxylase and in the ratio between the number of D1 and D2 receptors in the striatum. Moreover, the administration of 3 mg/kg of anandamide significantly decreased the contents of dopamine and L-3,4-dihydroxyphenylacetic acid in the striatum although lesser and higher doses were less effective. THC only tended to decrease these parameters. No changes were seen in dopaminergic activity in the limbic forebrain after either cannabimimetics. In summary, anandamide, as well as THC, decreases motor behavior. This effect was paralleled by reduction in the activity of nigrostriatal dopaminergic neurons. However, subtle differences in the behavioral and neurochemical effects between anandamide and THC could be observed. PMID- 7776830 TI - Pharmacological and behavioral evaluation of alkylated anandamide analogs. AB - Anandamide (arachidonylethanolamide), isolated from porcine brain, has been shown to bind to the cannabinoid receptor and also to produce cannabimimetic activity in pharmacological assays. This study examined structure-activity relationships in alkylated anandamide analogs. The analogs were evaluated for their ability to displace [3H]CP-55,940 in a filtration binding assay using rat brain membranes in the presence and absence of the enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). Behavioral activity was assessed by the ability of the analogs to produce hypomotility and antinociception. Methylations at carbons 2 and 1 produced compounds stable in the absence of PMSF with similar affinities and behavioral activity as anandamide. Addition of larger alkyl groups at these positions or nitrogen methylation reduced receptor affinity and behavioral potency. These results indicate that methylations at specific carbons of anandamide confer stability in vitro. PMID- 7776831 TI - Evaluation of cAMP involvement in cannabinoid-induced antinociception. AB - It has been proposed that cannabinoids act at a Gi protein-coupled receptor to produce antinociception. One action of Gi-proteins is to decrease intracellular cAMP via inhibition of adenylyl cyclase activity. Although cannabinoid inhibition of forskolin-stimulated adenylyl cyclase is used as a confirmation of functional cannabinoid receptors, it is unknown whether this second messenger system specifically mediates cannabinoid-induced antinociception. This in vivo study was conducted using enantiomeric cAMP analogs, Rp-cAMPS (an antagonist) and Sp-cAMPS (an agonist), and the cAMP agonist Cl-cAMP to test the hypothesis that cannabinoid-induced antinociception is due to decreased adenylyl cyclase activity. None of the cAMP analogs, forskolin, or 1,9-dideoxy-forskolin affected delta 9-THC or CP-55,940-induced antinociception produced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injections in mice. Experiments were also conducted to investigate whether i.c.v. administration of Sp-cAMPS would block i.c.v. cannabinoid-induced antinociception in rats. Sp-cAMPS failed to block CP 55,940-induced antinociception. However, Sp-cAMPS produced hyper-excitability and reactive behavior indicating that it did elicit a pharmacological effect. Although, adenylyl cyclase may mediate other cannabinoid-induced actions, these results do not support the hypothesis that it is involved in cannabinoid-induced antinociception. Alternatively, other effector systems such as calcium or potassium channels coupled to cannabinoid receptors may mediate cannabinoid induced antinociception. PMID- 7776832 TI - Effects of anandamide (endogen cannabinoid) on anterior pituitary hormone secretion in adult ovariectomized rats. AB - It has been shown that the main psychoactive component of marihuana, delta 9 tetrahydrocannabinol (THC) has mainly inhibitory effects on pituitary luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) and has no or little effect on follicle stimulating hormone (FSH) secretion. Recently the purification and availability of the putative endogenous ligand for the cannabinoid receptor, anandamide (arachidonyl ethanol-amide, anandamide) (ANA) provided us the opportunity to compare the effects of THC and ANA on the female neuroendocrine system in ovariectomized (OVX) rats. OVX was performed three weeks prior to the experimental period to avoid cyclic differences. OVX rats were injected i.p. with either THC or ANA (0.02 mg/kg.b.w./day, respectively) or vehicle for two weeks. The results show that both ANA and THC decrease serum LH level although THC with a higher degree. No significant differences were observed in serum FSH level. Both drugs decreased serum PRL. Serum GH was increased after THC administration and significantly decreased after ANA. The results indicate that ANA and THC alter pituitary hormone secretion, mainly by inhibitory action. The site of action requires further investigations. PMID- 7776834 TI - Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. AB - The rewarding property of delta 9-tetrahydrocannabinol (THC), the psychoactive constituent of marijuana and hashish, was studied using the conditioned place preference paradigm, and compared to that of cocaine, morphine, and food reward. The results of Experiment 1 demonstrated that 2.0 and 4.0 mg/kg doses produced a reliable shift in preference for the THC-paired compartment. The THC place preference observed at 2.0 and 4.0 mg/kg was nearly equivalent to that produced by low doses of cocaine (5.0 mg/kg), morphine (4.0 mg/kg), and food in non food deprived animals. The second experiment used a different conditioning procedure that included a washout period for THC. The results of Experiment 2 demonstrated that a THC place preference could be obtained using a lower dose of THC (1.0 mg/kg), and that this THC place preference was equivalent to that produced by 10 mg/kg cocaine. At higher doses (2.0 and 4.0 mg/kg), THC produced a dose-dependent place aversion. These results suggest that THC's action on brain reward substrates, previously demonstrated by electrical brain stimulation reward, in vivo brain microdialysis, and in vivo brain electrochemistry studies, reflects itself behaviorally in increased appetitive motivational value for environmental stimuli associated with ingestion of marijuana and hashish. PMID- 7776833 TI - Anandamide inhibits macrophage-mediated killing of tumor necrosis factor sensitive cells. AB - Anandamide (arachidonoylethanolamide) was shown to inhibit macrophage-mediated killing of tumor necrosis factor-sensitive murine L929 fibroblasts. Scanning electron microscopy (SEM) demonstrated that L929 cells, co-cultured with Propionibacterium acnes (P. acnes)-activated peritoneal macrophages from mice treated with vehicle, were either disrupted or had surface abnormalities and numerous punctate lesions. In contrast, L929 cells co-cultured with macrophages from mice receiving P. acnes in concert with Anandamide (20 mg/kg-80 mg/kg) or the exogenous cannabinoid delta-9-tetrahydrocannabinol (THC; 80 mg/kg) did not exhibit ultrastructural abnormalities. Cytotoxicity assays were performed in parallel with SEM in order to determine whether ultrastructural observations correlated with target cell killing as measured by release of radiolabel from L929 target cells. P. acnes-activated macrophages from vehicle-treated mice elicited 41% specific release of radiolabel from [51Cr]-labeled L929 cells. In contrast, macrophages from animals treated with P. acnes and with 20, 40, or 80 mg/kg Anandamide exhibited 38%, 25%, or 28% specific release of radiolabel, respectively. Similarly, macrophages from animals treated with P. acnes and with 80 mg/kg THC exhibited 21% specific release of radiolabel. In vitro cytotoxicity studies using radiolabeled L929 target cells and conditioned medium from RAW264.7 murine macrophage-like cells allowed for determination of the time interval over which Anandamide exerted its inhibitory effect. Maximal inhibition of target cell killing occurred when conditioned medium was obtained from macrophages exposed to Anandamide for 1 hr prior to activation. In contrast, conditioned medium from THC treated macrophages exerted its maximal inhibition of target cell killing when obtained from RAW264.7 cells pretreated for 24hr-48hr prior to activation. These results indicate that Anandamide and THC exert a similar inhibition of killing of TNF-sensitive target cells. However, the time interval over which these two substances elicit their suppressive effect differs. PMID- 7776835 TI - Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium "A-current" in cultured rat hippocampal neurons. AB - Cannabinoid receptor agonists have been previously shown to enhance a potassium A current (IA) in cultured rat hippocampal neurons. This effect has been further demonstrated to be dependent on G-protein linkage to adenylyl cyclase and levels of intracellular cyclic AMP (cAMP). The present study extends this analysis to the involvement of cAMP-dependent protein kinase (PKA) in this cascade. Specific activators and inhibitors of PKA were shown to have differential effects on the voltage dependence of IA. Specific activators of PKA produced a negative shift in voltage dependence of IA, whereas PKA inhibitors produced a positive shift in IA voltage dependence, the latter similar to that effected by the cannabinoid agonist WIN 55,212-2. Although the negative shift in IA induced by PKA stimulation could be reversed by PKA inhibitors, the positive shift produced by the PKA inhibitors alone was only 50-60% of the cannabinoid-produced shift in IA voltage dependence. This partial effect of PKA inhibition was confirmed by biochemical assays in the same cultured neurons that showed a similar 50-60% decrement in in vitro protein phosphorylation produced by PKA inhibitors. Results are discussed in terms of a diffusible second messenger linkage of the cannabinoid receptor to the A-current channel via the role of protein phosphorylation in modulation of IA. PMID- 7776836 TI - Metabolism of delta 9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys. AB - The most abundant metabolite of delta 9-tetrahydrocannabinol (delta 9-THC) formed with hepatic microsomes of monkeys was 11-OH-delta 9-THC, followed by 8 alpha-OH , 8 beta-OH- and 3'-OH-delta 9-THCs. Two cytochrome P450 isozymes, P450RM-A and P450JM-C, were purified from monkey hepatic microsomes and found to have a molecular weight of 51,000. In the reconstituted system, the activities of P450RM A towards formation of 11-OH-, 8 alpha-OH-, 8 beta-OH- and 3'-OH-delta 9-THCs were 19-, 40-, 22- and 10-fold higher, respectively, than the corresponding activities of the hepatic microsomes. The activity of P450JM-C towards formation of 3'-OH-delta 9-THC was 10-fold higher than that of P450RM-A, while the activities of both isozymes for 11- and 8 alpha-hydroxylation were not so much different and the 8 beta-hydroxylation activity was 14-fold higher in P450RM-A than in P450JM-C. Antibodies against P450RM-A and P450JM-C markedly inhibited the microsomal formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9 THC, respectively. These results suggest that P450RM-A and P450JM-C are major isozymes responsible for the formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9-THC, respectively, in monkeys. PMID- 7776837 TI - An efficient new cannabinoid antiemetic in pediatric oncology. AB - Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9 THC), was administered (18 mg/m2 in edible oil, p.o.) to eight children, aged 3 13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible. PMID- 7776838 TI - An examination of the central sites of action of cannabinoid-induced antinociception in the rat. AB - Microinjections of low doses of the potent and selective cannabinoids WIN 55,212 2 and CP 55,940 into the lateral ventricle produce long-lasting reduction in sensitivity to noxious thermal stimuli (1). To determine the central distribution of ventricularly administered WIN 55,212-2, we microinjected an analgesic dose of the drug with [3H]WIN 55,212-2. At the peak time of antinociception, the radiolabeled drug was confined to periventricular sites throughout the brain. The contribution of particular periventricular structures to the antinociceptive effect was evaluated using intracerebral microinjection techniques and the tail flick test. Guide cannulae were implanted above the following periventricular structures: the medial septal area, lateral habenlua, perihypothalamic area, arcuate nucleus of the hypothalamus, dorsal raphe nucleus and the dorsolateral and ventrolateral aspects of the periaqueductal gray. Microinjections of WIN 55,212-2 (5 micrograms/0.5 microliter) into the medial septal area, lateral habenula, perihypothalamic area, arcuate nucleus, and ventrolateral periaqueductal gray did not significantly affect tail-flick latencies. By contrast, microinjections of WIN 55,212-2 into the dorsolateral periaqueductal gray and the dorsal raphe significantly elevated tail-flick latencies. The results of this study indicate that at least two periventricular structures within the brain are involved in cannabinoid antinociception. PMID- 7776839 TI - Inhibition of noxious stimulus-evoked activity of spinal cord dorsal horn neurons by the cannabinoid WIN 55,212-2. AB - The effects of a potent synthetic cannabinoid WIN 55,212-2 on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in anesthetized rats. WDR neurons were identified by their responses to innocuous brushing and to a range of pressure stimuli from innocuous to noxious. Noxious pressure was applied to regions of the ipsilateral hind paw corresponding to the receptive field of the neuron. WIN 55,212-2 (125 micrograms/kg and 250 micrograms/kg, i.v.) produced a profound inhibition of firing evoked by the noxious pressure stimulus. By contrast, the cannabinoid did not alter the evoked activity of non-nociceptive neurons in response to non noxious levels of stimulation. Treatment with either vehicle or the inactive enantiomer WIN 55,212-3 (250 micrograms/kg) failed to alter noxious stimulus evoked activity of WDR neurons. These data provide direct evidence for cannabinoid-mediated inhibition of pain neurotransmission in the spinal dorsal horn. The site of action for these effects remains to be determined. PMID- 7776840 TI - Do cognitive impairments recover following cessation of cannabis use? AB - Our previous research with long term cannabis users established an impaired ability to focus attention and filter out irrelevant information, which was progressive with the cumulative duration of exposure to cannabis. The current study examined these processes in a group of ex-cannabis users. The results suggested a partial recovery of function but the past duration of cannabis use continued to have an adverse effect on the ability to effectively reject complex irrelevant information. There was no indication of improvement with increasing length of abstinence. Whilst relatively subtle in nature, the consequences of such an enduring deficit associated with cannabis use are worthy of further investigation. PMID- 7776841 TI - Biopsychosocial changes associated with cessation of cannabis use: a single case study of acute and chronic cognitive effects, withdrawal and treatment. AB - A 35 year old male was cognitively assessed prior to cessation of 18 years of daily cannabis use and monitored for several weeks post cessation. Brain event related potential (ERP) measures of selective attention reflecting a difficulty in filtering out complex irrelevant information showed no indication of improvement over 6 weeks of abstinence. In contrast, when tested in the acutely intoxicated state prior to cessation of use, a dramatic normalisation of the ERP signature of this individual was observed. A treatment program based on supportive-expressive psychotherapy was administered and depression, anxiety and general psychological health were monitored over the course of withdrawal from cannabis. PMID- 7776842 TI - Auditory and visual P300 event related potentials are not altered in medically and psychiatrically normal chronic marihuana users. AB - Attempts to use Event Related Potentials, particularly the cognitive or P300 evoked potential, as measures of CNS effects of THC use have been infrequent and have produced inconsistent results. We published a pilot study in which psychiatric patient THC users had significantly prolonged auditory P300 latencies and reduced amplitudes as contrasted with non-users. Because psychiatric diagnoses and medication effects could not be controlled, we repeated the study with medically and psychiatrically normal subjects selected with extremely stringent exclusion criteria and screening procedures. P300 latency differences between THC users and controls were not detected. Using all subjects, THC users displayed reduced auditory and visual P300 amplitudes. However, when age differences between THC users and controls were removed, all significant P300 amplitude differences were removed as well. The contaminating effect of using psychiatric patients in THC research is discussed and the importance of using carefully screened normal subjects in studies of neurophysiological abuse drug effects is stressed. PMID- 7776843 TI - Specific thought patterns in chronic cannabis smokers observed during treatment. AB - Clinicians report that chronic cannabis users seem to have symptoms, such as mental confusion and memory problems when entering treatment. The present study systematizes observations that were made during treatment of cannabis users during and after cessation of cannabis use. Cognitive symptoms prior to cessation are described in the conceptual framework of cognitive categories in the I.Q. test. Normalization of these cognitive functions during therapy is discussed. PMID- 7776844 TI - Chronic cannabis use and the sense of coherence. AB - Chronic cannabis users undergoing therapy were tested using the Sense of Coherence scale to determine the extent to which patients showed improvements in perceived comprehensibility, manageability, and meaningfulness of life. Improvement was demonstrated between admission and the completion of therapy six weeks later. Post-treatment scores were in the range of control subjects. Users who had quit using cannabis for more than 40 days at admission, but who had not participated in therapy, had somewhat higher scores than those who had quit for 17 days or less at admission. Patients in a methadone treatment program had scores below norms and did not show improvement during treatment. Poly-drug abusers, who had undergone psychosocial treatment, had scores somewhat below normative scores. Improvement in chronic cannabis users is discussed in the context of cognitive and psychosocial problems associated with chronic cannabis use. PMID- 7776845 TI - Relationships between motivation and depression in chronic marijuana users. AB - The "amotivational syndrome" which has been associated with marijuana use has not been examined systematically in relation to marijuana use and mental health. Light and heavy users were solicited by personal contact. They were asked to complete anonymous questionnaires which measured marijuana, alcohol and cocaine use, perceived states during marijuana intoxication, depressive symptoms in the last year, the Orientation to Life Scale and a modified form of the Thematic Apperception Test, from which Need for Achievement, Affiliation and Power were assessed. Several group comparisons were made: Chronic heavy-users (medians: daily use for 6 years) with and without significant symptoms of depression within the last year were compared with Light users (medians: several times per month for 4.5 years) with and without significant symptoms of depression within the last year. Subjects in all groups reported similar ratings of intoxication (being stoned) during marijuana use. No differences were found in alcohol or cocaine use among the comparison groups. Scores on Need for Achievement were significantly lower in heavy users with depressive symptoms when compared with all other groups. No effects were found among groups in measures of the Need for Affiliation and the Need for Power. Both light and heavy users with symptoms of depression had significantly lower scores than those without depressive symptoms, on the overall Orientation to Life questionnaire and on each subscale measuring Meaningfulness, Manageability and Comprehensibility. These data suggest that amotivational symptoms observed in heavy marijuana users in treatment are due to depression. PMID- 7776846 TI - Long-term behavioral effects of perinatal exposure to delta 9 tetrahydrocannabinol in rats: possible role of pituitary-adrenal axis. AB - This work evaluated motor behaviors in adult male and female rats exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. The possibility that perinatal THC exposure induces sensitization to other drugs of abuse has also been addressed by evaluating morphine place preference conditioning (MPP) in the adult offspring. Maternal exposure to THC resulted in long-term effects on motor behaviors such as rearing, grooming and sniffing, in the adult offsprings of both sexes. Additionally, female offspring exposed to THC showed greater locomotor activity than controls, when measured using an actimeter. THC-exposed males exhibited an increased exploratory behavior in a plus-maze paradigm. When the adult animals were tested for MPP, THC-exposed offspring of both sexes exhibited an enhanced sensitivity to the rewarding effects of a moderate dose of morphine (350 micrograms/kg), an effect which was more marked in the males. These results showed that perinatal exposure to this psychoactive cannabinoid affected motor behaviors in the adult, suggesting a psychomotor activation very similar to that observed after gestational exposure to other drugs of abuse. A possible role of a THC-induced hypothalamus-pituitary adrenal (HPA) axis activation was also evaluated in the present study. THC exposed females exhibited higher levels of both corticotropin releasing factor (CRF-41) in the medial basal hypothalamus (MBH) and plasma corticosterone, whereas THC-exposed males showed the lower levels of both endocrine parameters. Since glucocorticoids are important modulators of both brain development, and adult brain function, these results indicate a possible role of HPA axis disturbances in the mediation of the behavioral effects described after perinatal THC exposure. PMID- 7776847 TI - The prenatal exposure to delta 9-tetrahydrocannabinol affects the gene expression and the activity of tyrosine hydroxylase during early brain development. AB - We have previously reported that the exposure of pregnant female rats to delta 9 tetrahydrocannabinol (THC) during the perinatal period affected the gene expression and the activity of tyrosine hydroxylase (TH) in the brain of their male offspring. Those studies were done in animals perinatally exposed to THC but tested at peripubertal and adult ages. In the present work, we explored whether these effects also appear during early fetal brain development, when TH expression plays an important role in neuronal development. To this end, TH-mRNA concentrations were measured by Northern blot analysis with a specific TH probe in the brain of fetuses at gestational days 14 and 16 which had been prenatally exposed to THC or vehicle from day 5 of gestation. In parallel, measurements of TH activity and catecholamine contents by HPLC were also done. The results obtained were as follows. The prenatal exposure to THC markedly affected the expression of the TH gene in the brain of fetuses at gestational day 14. Thus, the amounts of TH-mRNA at this age were higher (2-fold) in THC-exposed fetuses than in controls. This corresponded with a marked increase in the activity of this enzyme (3-fold) at this age. Normalization was found in both parameters at gestational day 16. In summary, the prenatal exposure to THC affected the expression of the TH gene and the activity of this enzyme in brain catecholaminergic neurons during early fetal brain development. These results support the notion that cannabinoids are able to act at the level of the gene expression of specific key proteins for brain development. PMID- 7776848 TI - The relationship of tobacco and marijuana smoking characteristics. AB - In an ongoing study of the pulmonary effects of heavy, habitual marijuana smoking, detailed marijuana and tobacco smoking histories were obtained from 467 adult regular smokers of marijuana and/or tobacco. Frequency and cumulative amounts of tobacco and marijuana smoking were similar for smokers and nonsmokers of tobacco, except that pack-years and cigarettes/day at the time of the interview were both significantly less for tobacco smokers who also smoked marijuana compared those who did not. For all subjects who smoked both substances at any time, changes in tobacco and marijuana smoking amounts after commencement of regular smoking of the other substance were similar for tobacco and marijuana; the existing smoking habit decreased in approximately one third of the subjects and remained the same in slightly more than one half of the subjects. Of the dual smokers, 49% began smoking tobacco before marijuana, while 33% began smoking marijuana first; 85% of marijuana smokers who quit tobacco smoking did so after beginning regular marijuana smoking. Self-reported depth of inhalation and breath holding time of marijuana smoke were similar for tobacco and non-tobacco smokers; smoking topography for tobacco was also comparable for smokers and non-smokers of marijuana. PMID- 7776849 TI - Acute and chronic effects of marijuana smoking on pulmonary alveolar permeability. AB - Pulmonary clearance of technetium (99mTc)-labeled diethylene triamine pentaacetate (DTPA), a sensitive test of alveolar epithelial permeability, was measured twice in 34 healthy subjects, including 10 control nonsmokers (NS), 10 habitual smokers of marijuana alone (MS) (> or = 10 joints/wk), 9 regular smokers of tobacco alone (TS) (> or = 15 cigarettes/day) and 4 habitual smokers of both marijuana and tobacco (MTS). In smokers, the first study was performed after > or = 12 hrs of abstinence from smoking to assess chronic effects of marijuana and/or tobacco smoking on alveolar permeability; the second study was performed within 15 min of smoking to assess possible acute effects. TS exhibited abnormally rapid 99mTc-DTPA clearance after > or = 12 hours of abstinence, indicating an increase in pulmonary epithelial permeability, consistent with chronic tobacco-induced lung injury. MS showed a more modest and less consistent chronic effect than TS on 99mTc-DTPA clearance, suggesting a more variable and smaller degree of marijuana-induced lung injury. No acute effect of tobacco or marijuana smoking on 99mTc-DTPA clearance was apparent. Concomitant habitual smoking of marijuana and tobacco had no additive effect on alveolar permeability. PMID- 7776851 TI - Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats. AB - Earlier data from experiments in rats have shown that administration of retinyl esters (vitamin A) strongly influences the effects of CCl4 on the liver. The accumulation of collagen was inhibited, but an increase in CCl4-toxicity with high mortality was observed. The present study was conducted to examine the effects of beta-carotene (provitamin A) on CCl4-related general and hepatic toxicity in rats. Oral administration of beta-carotene during CCl4-treatment resulted, biochemically, in a significantly lower increase in the hydroxyproline liver content and, histopathologically, in less severe liver fibrosis as compared with the liver of rats not treated with beta-carotene. The study also showed that beta-carotene administration could prevent the long-term loss of retinoids from the CCl4-injured liver. No significant toxic effects of beta-carotene, as previously found with retinyl esters (vitamin A), were observed. This experimental study suggests that beta-carotene has the therapeutic potential to decrease the severity of liver fibrosis without marked toxicity. PMID- 7776850 TI - Effects of smoking marijuana, tobacco or cocaine alone or in combination on DNA damage in human alveolar macrophages. AB - This study examined the role of marijuana smoking in the pathogenesis of human lung cancer by measuring DNA damage in alveolar macrophages (AM). The alkaline unwinding method was used to determine DNA single-strand breaks in AM lavaged from non-smokers [NS] and smokers of marijuana [MS], tobacco [TS] or cocaine [CS], either alone or in combination. DNA damage was related to superoxide anion (O2-) production by AM stimulated with phorbol myristate acetate (PMA) and to nitric oxide content of smoke using cellular nitrite (NO2-) concentrations. The percentage of double-stranded DNA present after alkaline unwinding was higher in AM of NS (41 +/- 5% [11]) and CS (41 +/- 4% [9]) versus that of MS (31 +/- 4% [8]), TS (35 +/- 3% [11]), MTS (26 +/- 4% [3]), and CTS (27 +/- 5%* [10]), mean +/- SEM [n], * = p < 0.1 vs. NS). PMA stimulated O2- production by AM from NS and CS was lower than that of other smokers, but the differences were not significant. O2- release, however, had an inverse correlation with DNA single strand breaks (r = -0.38, p = 0.009). Nitrite content of AM from NS and CS was less than that of other smokers' cells (p < 0.1 for TS & CTS vs. NS), but DNA damage had no relationship to NO2- concentration. We conclude that AM recovered from MS, either alone or in combination with tobacco smoking, show a trend towards DNA damage. Studies utilizing a larger population should verify our findings and further define its relationship to enhanced oxidant production by macrophages. PMID- 7776852 TI - Protective effect of diltiazem against acetaminophen hepatotoxicity in mice. AB - There is evidence that an increase in cytosolic Ca++ concentration is a terminal event in the progression to cell death in toxic liver injury. We have compared the hepatoprotective effects of N-acetylcysteine (1 g/kg) and the calcium channel blocking agent, diltiazem (24 mg/kg), when given at 30 min, 3 h and 6 h after single intraperitoneal overdoses of acetaminophen (500 mg/kg) in mice. Overall beneficial effects on mortality, liver necrosis score, and plasma alanine aminotransferase (ALT) activity were found in diltiazem-treated mice 24 h after acetaminophen overdose. However, the most marked effects were obtained when diltiazem was given 6 h after acetaminophen. N-acetylcysteine was more effective than diltiazem at 30 min and 3 h, although it was less effective at 6 h. Mean plasma concentrations of the mercapturate metabolite (hepatic oxidative metabolism) were not significantly different among animals receiving acetaminophen alone or in combination with diltiazem, which suggests that the hepatoprotective effects of diltiazem are not exerted by inhibition of drug metabolic enzymes. PMID- 7776854 TI - Severe hepatotoxicity related to benzarone: a report of three cases with two fatalities. AB - We report three cases of severe hepatotoxicity related to benzarone, a benzofuran derivative. Our cases include a 35-year-old woman with (sub)fulminant hepatitis, a 67-year-old woman with macronodular cirrhosis, and a 68-year-old man with severe chronic active hepatitis and cirrhosis, with positivity of anti-smooth muscle antibodies. Two patients died. We stress the potential of benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related to benzarone. PMID- 7776853 TI - Lymphoblastoid interferon therapy in chronic hepatitis C: biochemical, virological and histological evaluation of two different doses. AB - Sixty patients of both sexes with biopsy-proven chronic hepatitis C were randomized to receive lymphoblastoid interferon 3 MU or 6 MU three times weekly for 6 months. A follow-up period of 3 months at the end of the therapy was scheduled. Thirty-two patients (53.3%) normalized alanine aminotransferase at the end of the therapy. Of these, 17 received 3 MU (56.7%) and 15 (50%) received 6 MU. Eighteen of the 32 patients (56.2%) relapsed in the follow-up period after treatment. No significant difference in relapse rate was observed between the two groups. The overall percentage of the non-responder patients was 36.6%. The treatment was discontinued because of non-compliance and/or side effects in six patients (10%): three in the 3-MU group and three in the 6-MU group. An improvement in liver histology was observed in about a quarter of chronic active hepatitis patients whose overall diagnosis changed to chronic persistent hepatitis. Knodell's score system showed a significant improvement (p < 0.05) with regard to peripheral necrosis, fibrosis and total score. HCV-RNA was positive at the beginning in all patients and it became undetectable in almost all responder patients. In some cases there was no correlation between viraemia and biochemical signs of liver disease. Our study shows that 6 MU does not increase the response rate compared to 3 MU. Moreover, the lower dose is able to improve the liver histology and to abolish the HCV viraemia in responder patients. PMID- 7776855 TI - The role of the spleen in endotoxin-induced liver injury. AB - In these experiments, the role of the spleen in endotoxin-induced liver injury was evaluated, using rats which underwent splenectomy or splenic vein ligation with antecedent spleno-systemic shunt. Male Wistar rats were divided into three groups: a sham-operated group, a splenectomy group, and a splenic vein ligation group. In each animal, 48 h after surgery, 5 mg/kg lipopolysaccharide (LPS) were injected intravenously. Six rats from each group were sacrificed 6 or 12 h after LPS administration. Bronchoalveolar lavage fluid (BALF) and arterial blood were also collected. Splenectomy reduced the liver injury as indicated by the serum lactate dehydrogenase level. A decrease in liver tissue adenosine triphosphate and increase in lipid peroxide were induced by LPS administration and inhibited by splenectomy. Splenectomy also reduced alveolar protein release as indicated by the protein level in BALF. Splenic vein ligation provided similar protective effects on the liver, but did not affect lung injury. From these results, it appears that the spleen plays a significant role in endotoxin-induced liver injury, and a mediator derived from the spleen is likely associated with development of liver injury. This mediator may be cleared or inactivated by not only splenectomy but also splenic vein ligation. PMID- 7776856 TI - Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis. AB - Mannan-binding protein is synthesized by the liver and functions in first-line host defence by opsonizing mannose-rich microorganisms due to activation of the classical complement pathway independent of Clq, and by an intrinsic ability to opsonize and mediate phagocytosis. We have investigated whether the increased susceptibility to bacterial infections in patients with cirrhosis could be explained by low plasma concentrations of mannan-binding protein and impaired complement-dependent opsonization. We examined 51 patients with compensated alcoholic cirrhosis, 34 who were decompensated and 16 healthy controls. Irrespective of group, we found a significant correlation (p < 0.05) between plasma mannan-binding protein concentration and deposition of the complement opsonin C4 on mannan from baker's yeast. In contrast to what was expected, this kind of opsonization and plasma levels of mannan-binding protein were significantly increased in the patients with decompensated cirrhosis (p = 0.01 and p = 0.007, respectively). A significant correlation (0 < 0.05) was found between mannan-binding protein and erythrocyte sedimentation rate, fibrinogen and haptoglobin in these patients. Though the correlations were weak (rho = 0.49, rho = 0.48 and rho = 0.40, respectively), the elevated levels of mannan-binding protein in the patients with decompensated cirrhosis may reflect an acute phase reaction. It is concluded that plasma levels of mannan-binding protein are increased in patients with decompensated cirrhosis and that complement-dependent opsonization of mannan does not seem to be compromized in patients with alcoholic cirrhosis. PMID- 7776857 TI - The French experience of treatment of chronic type D hepatitis with a 12-month course of interferon alpha-2B. Results of a randomized controlled trial. AB - Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon-a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon-a2b subcutaneously three times weekly for 12 months (5 MU/m2 for 4 months and then 3 MU/m2 for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV-RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/or virological relapse over the 6-month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon-a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric side effects. PMID- 7776858 TI - Association of primary sclerosing cholangitis, thymoma and hypogammaglobulinemia. AB - A 64-year-old Japanese woman with thymoma has been suffering from diarrhea and increased alkaline phosphatase levels without jaundice. Her serum immunoglobulin levels of IgM and IgG were less than half of the normal levels, with an increase in CD8 (suppressor/cytotoxic) T cell percentage and a decrease in CD4 (helper) T cell percentage, resulting in a lower CD4/CD8 ratio of 0.31. These immunological features are in accordance with those of hypogammaglobulinemia complicating thymoma. Cholangiography and a liver biopsy specimen disclosed the presence of primary sclerosing cholangitis (PSC). PSC has been recognized in various immunodeficiency syndromes and this case shows that thymoma complicated by hypogammaglobulinemia is associated with PSC. PMID- 7776859 TI - The vulnerabilities of mentally disordered witnesses. PMID- 7776862 TI - Representing and analysing the interviewee's account. PMID- 7776860 TI - The influence of witness appearance and demeanour on witness credibility: a theoretical framework. PMID- 7776861 TI - Quality investigation? Police interviewing of witnesses. PMID- 7776863 TI - Recording and disclosing statements by witnesses--law and practice. PMID- 7776864 TI - The admissibility of expert psychiatric and psychological evidence. Judicial training. PMID- 7776865 TI - Violent incidents in an adolescent forensic unit. AB - Violent incidents in psychiatric institutions have been the focus of much study over the past few decades. But there has been little work looking at similar incidents in child and adolescent units. The authors set out to examine whether some of the patterns observed in adult populations are true of adolescent groups. The Gardener Unit was considered appropriate in light of reports of a higher frequency of assaultative behaviour among younger clients and because of the nature of problems presented by clients needing a secure environment. All violent incidents are automatically recorded. The violent incident register was examined between 1 June 1991 and 1 June 1992 and the information cross-checked with case notes and nursing reports. Demographic details, etc. were obtained from case notes. The results indicated a slightly higher daily incident rate than adult studies. At least half of the population were involved in some form of violent episode over the 12-month period. The majority of incidents were minor in nature. Nursing staff were the most frequent targets, although females showed an excess of inwardly directed aggression (self harm). A prior history of violent behaviour did not serve as a realistic predictor of frequency of violent incidents in this study. With increasing concern regarding the care of this disturbed group of young people, it was felt important to look closely at the nature of and handling of violent incidents on this unit. A second paper will consider in detail how these incidents were dealt with. PMID- 7776866 TI - Mentally incapacitated adults and decision-making: a psychological perspective. Comments on Law Commission consultation papers, numbers 128, 129 and 130. AB - The law commission is currently proposing new legislation to protect the rights of mentally incapacitated adults. This paper describes, briefly, the proposed legislation. The author notes that the proposed legislation relies on categories established for the purposes of the Mental Health Act, 1983, which is itself under revision, and that these categories fail to capture the full range of cases to which the proposed legislation is intended to apply. The author suggests the use of more established international classification schemes which may be more readily understood across the European Community. Further, the author draws attention to developments in psychological theory and methodology, and urges the adoption of scientific methods in the assessment of cognitive incapacity, and in the more general application of the proposed legislation. PMID- 7776867 TI - Routine use of ultraviolet light in medicolegal examinations to evaluate stains and skin trauma. AB - The use of ultraviolet light induced fluorescence as an aid in forensic medical examinations of rape victims was evaluated preliminarily in a retrospective, non consecutive study. In a four-month period, 17 cases were referred by the police for examinations at the Institute of Forensic Pathology. Ultraviolet light illumination (UVI) was used in seven cases, and in six cases fluorescent skin areas were observed. The fluorescence was due to lesions in four cases and stainings with saliva and semen in other two cases. In at least two cases, skin trauma detected with UVI were unobserved in ordinary light. It is concluded that UVI should be a routine part of forensic medical examinations. It may assist the forensic medical examiner in finding skin trauma and in locating stains, thus enabling retrieval of material for serological analyses. UVI is simple to carry out, requiring only a small, portable ultraviolet light source. PMID- 7776868 TI - Neuroleptic induced sudden death--a case report and critical review. AB - A case report illustrates possible pathophysiological mechanisms of sudden death in psychiatric patients. Difficulties with the tendency to implicate phenothiazines as the cause of death are discussed in light of evidence that the death investigation and autopsy are often incomplete. Some suggestions are made to reduce the risk of a fatal outcome following a violent incident. PMID- 7776869 TI - Suicide by self-strangulation whilst under observation. AB - Two cases are reported of individuals who committed suicide after they had been identified as being acutely at risk of killing themselves. Self-strangulation by a ligature fashioned from the subjects' clothes was the mechanism of suicide in both cases. One death occurred in a police station and the other on an acute psychiatric ward. These cases highlight the need for those formulating policies concerning the supervision of the suicidal individual to pay attention to the minutiae of detail. In particular, a case is made for those at risk of suicide to be prevented from sleeping with their head covered by blankets. PMID- 7776870 TI - Forensic investigations in an arson case. AB - A case of arson is presented from the State of Himachal Pradesh, India. The case was initially reported as an accidental fire due to electrical short circuiting but was suspected by the police to be arson as Government money worth 1.32 lakh rupees was also stated to have been burned in the fire. Forensic investigations proved the case to be arson but no currency notes had been burned in the fire. PMID- 7776872 TI - Eye-witness testimony and judicial studies. PMID- 7776871 TI - Successful suicide by insulin injection in a non-diabetic. PMID- 7776873 TI - Contamination of witness memory in theory and practice. PMID- 7776874 TI - 42nd Meeting of the American College of Sports Medicine. Minneapolis, Minnesota, May 31-June 3, 1995. Abstracts. PMID- 7776875 TI - Three-dimensional spectroscopic imaging with time-varying gradients. AB - A spectroscopic imaging sequence with a time-varying readout gradient in the slice selection direction is used to image multiple contiguous slices. For a given voxel size, the imaging time and signal-to-noise ratio of the three dimensional spectroscopic sequence are the same as for a single slice acquisition without the oscillating readout gradient. The data reconstruction employs a gridding algorithm in two dimensions to interpolate the nonuniformly sampled data onto a Cartesian grid, and a fast Fourier transform in four dimensions: three spatial dimensions and the spectral dimension. The method is demonstrated by in vivo imaging of NAA in human brain at 1.5 T with 10 slices of 16 x 16 pixels spectroscopic images acquired in a total scan time of 17 min. PMID- 7776876 TI - Interpretation of 31P MRS spectra in determining intracellular free magnesium and potassium ion concentrations. AB - The current paper develops a simple mathematical model for the determination of the concentration of ionic species using the chemical shifts of ATP from phosphorus magnetic resonance spectroscopy (31P MRS) spectra. An iterative method is used to evaluate the equilibrium constants for a range of Mg/ATP equilibria. Initially, an expression for free magnesium concentration is determined by consideration of four equilibria. We then demonstrate how any number of equilibria may be included using this simplified analysis, by incorporation of pseudo equilibrium constants. This approach may be applied to the interpretation of both ex vivo and, more importantly, in vivo MRS spectra. Furthermore, the authors suggest that the commonly used equation for determining free intracellular magnesium concentration as presented by Gupta and colleagues is an oversimplification, particularly under conditions of fluctuating pH. PMID- 7776877 TI - A model for magnetization transfer in tissues. AB - Magnetization transfer in several tissues is measured and successfully modeled using a two-pool model of exchange. The line shape for the semi-solid pool is characterized by a superLorentzian and the liquid pool by a Lorentzian. The tissues investigated were white and gray matter, optic nerve, muscle, and liver. All tissues the authors studied are characterized by the same model but differ in the parameter values of the model. Blood and cerebral spinal fluid (CSF) were also investigated. The two-pool model with a Lorentzian line shape for both the semi-solid and liquid pools modeled the magnetization transfer in blood. In CSF, as expected, there is no measurable exchange of magnetization. The T2B associated with the semi-solid pool was short (approximately 10 microseconds) for all tissues indicating a fairly rigid semi-solid pool. In addition characterization of the line shape as superLorentzian indicates molecules such as integral membrane proteins or lipids in membranes are likely molecules participating in the exchange. Conversely, in blood large globular proteins are indicated due to the Lorentzian nature of the semi-solid pool and a T2B approximately 300 microseconds. PMID- 7776878 TI - Action of compression and cations on the proton and deuterium relaxation in cartilage. AB - In this paper, investigations are described on the influence of osmotic pressures and of varying cation concentrations on water relaxation times in cartilage (pig articular cartilage and bovine nasal cartilage). Both water content and relaxation times decrease strongly with increasing osmotic pressure. This relaxation behavior can be explained in terms of a fast chemical exchange between unbound and bound water. Na+ does not influence water content or relaxation times, whereas Ca2+ causes a small reduction in these parameters. PMID- 7776879 TI - Magnetization transfer and T2 relaxation components in tissue. AB - T2 relaxation makes an important contribution to tissue contrast in magnetic resonance (MR) imaging. Many tissues are known to exhibit multicomponent T2 relaxation that suggests some compartmental segregation of mobile protons on a T2 timescale. Magnetization transfer (MT) is another relaxation mechanism that can be used to produce tissue contrast in MR imaging. The MT process depends strongly on water-macromolecular interactions. To investigate the relationship between multicomponent T2 relaxation and the MT process, multiecho T2 measurements have been combined with MT measurements for freshly excised samples of cardiac muscle, striated muscle, and white matter. For muscle, short T2 components show greater MT than long T2 components, consistent with the belief that they represent distinct water environments. For white matter, quantitative MT measurements were identical for the two major T2 components, apparently because of exchange between the T2 compartments on a time-scale characteristic of the MT experiment. Implications for accurate modeling of MT in tissue and the use of MT for MR image contrast are discussed. PMID- 7776880 TI - Phase constrained encoding (PACE): a technique for MRI in large static field inhomogeneities. AB - In spin echo imaging, magnetization is assigned to a location defined by its frequency of rotation. In the presence of a static magnetic field inhomogeneity, however, this location does not correspond to the true location of the magnetization. This paper describes a magnetic resonance imaging technique called phase constrained encoding (PACE) that assigns magnetization to its true location through the use of a spin echo train and alternating readout gradients. Small artifactual side-bands occur in the point spread function but can be minimized or eliminated using higher gradient strengths, more echoes, and/or additional acquisitions. Implementation of a simple version of this technique confirms simulations. PMID- 7776881 TI - Pharmacokinetic mapping of the breast: a new method for dynamic MR mammography. AB - A dynamic contrast-enhanced MRI technique for whole breast examinations is presented. The fast kinetics of tissue response during and after constant-rate intravenous infusion of gadolinium diethylenetriaminopentaacetic acid was resolved using a strongly T1-weighted saturation recovery TurboFLASH sequence that makes it possible to acquire signal-time courses sequentially from 15 adjacent slices with a temporal sampling rate of 21 s. On the basis of the mathematically established and experimentally verified linear relationship between the measured saturation recovery TurboFLASH signal variation and the gadolinium diethylenetriaminopentaacetic acid concentration in the tissue, the signal-time courses were analyzed within the framework of pharmacokinetic modeling. In our study, the tissue response was parameterized adequately using an open linear two-compartment model. With this approach, the tissue specific information contained in the signal-time course can be described using only two parameters: an amplitude A, reflecting the degree of MR signal enhancement, and an exchange parameter k21, characterizing vascular permeability and perfusion of the tissue. A clearly arranged representation of the large amount of data (480 saturation recovery TurboFLASH breast images/examination) was accomplished by means of color coding of the computed parameters, resulting in one color-coded pharmacokinetic parameter map/cross-section. PMID- 7776882 TI - Intracellular volume measurement and detection of edema: multinuclear NMR studies of intact rat hearts during normothermic ischemia. AB - The present study describes the cell volume dynamics in intact rat hearts, during ischemia and after reperfusion. Cell volumes were measured in isolated hearts by either 13C or 59Co NMR of mannitol or cobalticyanide, respectively, as extracellular markers and 1H NMR of water as the aqueous space marker. A constant volume chamber was built inside a 15-mm NMR tube; the contents of the chamber were measured with and without a heart. The intracellular volume of isolated rat hearts was estimated to be 2.45 +/- 0.13 ml/g dry weight. In the perfused heart, adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations were calculated to be 12.2 +/- 0.7 and 16.1 +/- 1.0 mM, respectively. Consecutive volume measurements showed cell swelling of 16% during 30 min of ischemia, which was reduced at reperfusion to 7%. After 30 min of reperfusion, ATP and PCr concentrations were 4.5 +/- 0.8 and 8.1 +/- 0.9 mM. It is concluded that: (1) cell swelling is an ischemic event, which is partially reversed by reperfusion; and (2) continuous measurement of cell volumes provides intracellular molar concentrations of metabolites, which are the physiologically significant parameters. PMID- 7776883 TI - Susceptibility magnetic resonance imaging using spectral decomposition. AB - Susceptibility differences of materials in magnetic resonance imaging (MRI) usually lead to the intravoxel spin phase variations. Subsequently, the phase variation in the voxel results in a reduction of the signal intensity. This signal intensity reduction is known as the susceptibility effect in MRI and has been studied extensively. In this paper, a new spectral decomposition technique is proposed with which the signal change due to the susceptibility effect can be analyzed. Further, an NMR pulse sequence for the spectral decomposition of the susceptibility was developed and applied to susceptibility imaging of venous blood possessing paramagnetic properties. The computer simulations of the spectral decomposition method and their corresponding experimental results obtained using both a phantom and human volunteers are reported. PMID- 7776884 TI - GRASE improves spatial resolution in single shot imaging. AB - In single shot echo train imaging all the data required for a two dimensional image is acquired from a series of echoes generated following a single RF excitation pulse. Spatial resolution is limited because all samples must be acquired before the signal decays. In this paper we show theoretically that more echoes and hence better spatial resolution can be obtained with single shot GRASE imaging than with either echo planar imaging or single shot RARE imaging. This conclusion holds for both conventional imaging hardware and specialized gradient hardware designed for EPI. High quality single shot GRASE images support the theoretical conclusions. PMID- 7776885 TI - An algorithm for MR angiography image enhancement. AB - This study describes a three-dimensional (3D) filtering algorithm for magnetic resonance angiography (MRA) image enhancement. Based on the properties of 3D MRA data, the algorithm uses the dispersion range of the 13 outputs of a 3D directional low-pass filter bank to identify the vessel structure and control the processing of MRA data. Vascular structures in the data are preserved while the components of static tissues and isolated noise impulses are reduced by the processing. As a result, the small vessels have been enhanced and visibility of vessels in the projected image has been improved. PMID- 7776887 TI - A velocity k-space analysis of flow effects in echo-planar and spiral imaging. AB - A velocity k-space formalism facilitates the analysis of flow effects for imaging sequences involving time-varying gradients such as echo-planar and spiral. For each sequence, the velocity k-space trajectory can be represented by kv(kr); that is, its velocity-frequency (kv) position as a function of spatial-frequency (kr) position. In an echo-planar sequence, kv is discontinuous and asymmetric. However, in a spiral sequence, kv is smoothly varying, circularly symmetric, and small near the kr origin. To compare the effects of these trajectory differences, simulated images were generated by computing the k-space values for an in-plane vessel with parabolic flow. Whereas the resulting echo-planar images demonstrate distortions and ghosting that depend on the vessel orientation, the spiral images exhibit minimal artifacts. PMID- 7776886 TI - Respiratory blur in 3D coronary MR imaging. AB - 3D MR imaging of coronary arteries has the potential to provide both high resolution and high signal-to-noise ratio, but it is very susceptible to respiratory artifacts, especially respiratory blurring. Resolution loss caused by respiratory blurring in 3D coronary imaging is analyzed theoretically and verified experimentally. Under normal respiration, the width for any Gaussian point spread function is increased to a new value that is at least several millimeters (about 3-4 mm). In vivo studies were performed to compare respiratory pseudo-gated 3D acquisition with breath-hold 2D acquisition. On average, the overall quality of a pseudo-gated 3D image is worse than that of the corresponding breath-hold 2D image (P = 0.005). In most cases, respiratory blur caused coronary arteries in pseudo-gated 3D data to have lower resolution than in breath-hold 2D data. PMID- 7776889 TI - Quantitative analysis of dynamic Gd-DTPA enhancement in breast tumors using a permeability model. AB - The MRI signal enhancement in a breast tumor, measured as a function of time after a bolus injection of Gd-DTPA, may contain enough information to differentiate malignant from benign tissue. We find a physiological model for measuring capillary permeability and leakage space (P. S. Tofts, A. G. Kermode, measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn. Reson. Med. 17, 357-367 (1991)) fits the data well. The enhancement curve is particularly sensitive to the preinjection T1 of the tumor, the dose, and the time of injection. This model may provide a means of characterizing the pathophysiology of breast tumors from the Gd-DTPA enhancement curve. PMID- 7776888 TI - Quantitative combined phosphorus and proton PRESS of the brains of newborn human infants. AB - Techniques for quantitative, combined phosphorus and proton, point-resolved spectroscopy (PRESS) studies of newborn-infant brain have been developed. Phosphorus PRESS advantages include: voxel-shimming; rapid transmitter-pulse setting; novel use of brain-water as a localized quantitation reference; and reduced broad components. Proton spectra from 1-ml voxels and phosphorus spectra can both be acquired quantitatively within acceptable time. Cerebral lactate was consistently detected by proton PRESS and the normal concentration (approximately 3 mmol/kg wet weight) may be higher than in adult brain. Phosphorus PRESS provided metabolite peak-area ratios and concentrations comparable with those obtained using ISIS. PMID- 7776890 TI - Deuterium magnetic resonance imaging of rabbit eye in vivo. AB - We used deuterium magnetic resonance imaging (2H MRI) to visualize water movement in the rabbit eye. Dynamic 2H MRI was obtained every 3.5 min at 2 tesla by FLASH pulse sequence (TR, 300 ms; TE, 10 ms; alpha = 90 degrees) with a slice thickness of 10 mm using a surface coil (4 cm in diameter). After topical administration (0.2 ml D2O), only the aqueous chamber was imaged, and the signals decreased mono exponentially. The flow rate was 0.113/min, in agreement with that already reported. After intravenous administration of deuterated saline (3 ml/kg), the aqueous chamber became visible first during imaging, then by the vitreous body. The signals around the lens were only faintly detected. Thus, deuterium MRI was determined to be useful for visualizing water movement in the eye. PMID- 7776891 TI - Echo-time-encoded burst imaging (EBI): a novel technique for spectroscopic imaging. AB - A new technique for rapid spectroscopic imaging is presented. The proposed experiment enables a complete mapping of the two-dimensional reciprocal space kx, k sigma, and thus the acquisition of a 1D spectroscopic image in a single scan. The properties of the pulse sequence, based on the use of a burst of low flip angle pulses, are analyzed in the framework of linear response theory, and it is shown that chemical shift information may be introduced into the spatially encoded echoes. First experimental results are presented demonstrating that 32 x 32 proton spectroscopic images may be acquired within less than 1 min with a conventional imaging system. PMID- 7776892 TI - Quantitative mapping of ocular oxygenation using magnetic resonance imaging. AB - Retinal hypoxia is hypothesized to initiate angiogenesis, a leading cause of blindness in developed countries. Attempts to test this hypothesis suffer from the need to use highly invasive oxygen electrodes. In this communication, noninvasive and quantitative mapping of ocular oxygenation using magnetic resonance imaging is demonstrated for the first time. PMID- 7776893 TI - Susceptibility artifact reduction in fat suppression. AB - Strong fat signal in regions where a large susceptibility difference exists, for instance at the interface between air and tissue near the maxillary sinus, may not be eliminated by currently available fat suppression techniques without sacrificing the overall quality of the images. In this article, we show that this fat signal, which appears as a susceptibility artifact, can be significantly reduced by using an optimized presaturation pulse with sharp edges and a broad bandwidth, while causing minimal disturbance of the water signal. Several optimized presaturation pulses can be reproduced by the Fourier coefficients provided in the Appendix. PMID- 7776894 TI - Cumulative subject index. Volumes 195-198, 200-227. PMID- 7776896 TI - Sunspots and the recency theory of schizophrenia. AB - Schizophrenia, a disorder with a high, fairly uniform, global distribution, can occur with or without an accompanying family history of mental disorder. Given the preponderance of sporadic cases and the low fertility of genetic cases, this combination suggests that the disorder might be caused by a globally active teratogen. It has recently been shown that some factor associated with high sunspot activity acts transgenerationally to reduce lifespan. The following article discusses the relevance of that finding to changes in the incidence of schizophrenia and suggests that schizophrenia is caused by some factor associated with sunspots. PMID- 7776895 TI - The solution to the seven mysteries of AIDS: the 'Trojan horse'. AB - It is concluded that the sperm is the cause of AIDS but that HIV may slightly alter the symptoms of this disease, as compared to idiopathic CD4+ T lymphocytopenia, or ICL, where the sperm, but not HIV, is assumed present. In the proposed mechanism, the sperm selectively accepts into its interior only macrophage-tropic HIV through its CD4+ antigens and carries this HIV into a person through four possible pathways: rectum (anal sex), genital ulcers, blood transfusions, and female circumcision. Then the sperm acts as a 'Trojan horse' by entering HLA-DR+ CD4+ T cells and releasing the HIV into these cells. The released HIV in turn mutates to a form capable of attacking CD4+ T cells. Thus the sperm by a 'Trojan horse' mechanism has changed the tropism of HIV. However, experimental evidence indicates that this mutated HIV is essentially non-toxic. In contrast, it is concluded that the sperm is extremely toxic since it is capable of inducing autoimmune reactions (by means of its CD4+ antigens) and is capable of entering and destroying HLA-DR+ CD8+ and HLA-DR+ CD4+ T cells in either the presence or absence of HIV (AIDS or ICL). Hence, the mysteries of AIDS can be explained by the presence of the toxic sperm and its complicated interactions with HIV (the 'Trojan horse' mechanism). PMID- 7776897 TI - Preliminary evidence for idiotype-antiidiotype immune complexes cross-reactive with lymphocyte antigens in AIDS and lupus. AB - Several investigators have proposed that autoimmunity may be induced by idiotype antiidiotype antibody networks. It is generally assumed that the antiidiotype is produced in response to the idiotype, and therefore that autoimmune diseases have single antigenic initiators. The theory of multiple-antigen-mediated autoimmunity (MAMA) proposes, on the other hand, that idiotype and antiidiotype result from two primary immune responses to two chemically complementary antigens. Because of the complementarity of the antigens, and the complementarity of the antibodies for the antigens, the antibodies will themselves be complementary. They will thus form circulating immune complexes, the self-nonself distinction diffusion (DAD) experiments (a modification of Ouchterlony immunodiffusion), in which 1800 pairs of antibodies were screened for their ability to form precipitating complexes. Four sets of antibodies associated with AIDS (HIV + Staphylococcus; HIV + Mycoplasma; CMV + Mycoplasma; and HBV + Mycoplasma) specifically precipitated each other, and one of the antibodies in each set also precipitated monoclonal antibodies against one or more lymphocyte protein markers. These results therefore demonstrate that idiotype-antiidiotype antibodies can be elicited by independent antigens and may induce AIDS-related forms of autoimmunity directed at lymphocytes. PMID- 7776898 TI - The 'LXCXE' hydropathic superfamily of ligands for retinoblastoma protein: a proposal. AB - The present study reports structural similarities between viral oncoproteins, growth factors belonging to the insulin family, members of the steroid/thyroid receptor superfamily, a D-type cyclin, the Elf-1 transcription factor and Bcl oncoproteins in regions that have been shown or proposed to mediate complex formation of these proteins with the tumor suppressor retinoblastoma protein (RB). This relationship predicts a common intracellular pathway for mitogenic signals and molecules promoting cell survival. Conversely, the structural evidence described here suggests that RB may play a central role both at the boundary between negative and positive cell growth regulation as well as in developmental decisions between cell death and cell survival. PMID- 7776899 TI - Synthetic inducible biological response amplifiers (SIBRAs): rational peptides at the crossroads between molecular evolution and structure-based drug design. AB - The present study proposes a novel type of synthetic chimaeric polypeptides potentially useful in the therapy of various diseases. The prototype peptide termed 'synthetic inducible biological response amplifier' (SIBRA) would comprise a ligand-binding site, a DNA-binding region, a trans-activating domain as well as strings of residues ensuring bioavailability and targeting to specific compartments such as the cell nucleus. These domains would be selected from cellular proteins, artificially tailored to a SIBRA and further modified towards a molecule with both in vivo and intracellular activity. Since proposed to resemble a host molecule with autoregulatory properties, a SIBRA would be activated upon exposure to a defined environmental stimulus and amplify host responses appropriate for this stimulus. Proteins would accumulate that share functional domains with the administered SIBRA and have a positive autoregulatory capacity. The latter may involve the interaction of the induced protein with the promoter of its gene resulting in a direct positive autoregulatory loop or require the induction of intermediary proteins that eventually upregulate the production of SIBRA-like host proteins. Since the ligand-binding site of a SIBRA is rationally designed to target a pathogenic protein, SIBRAs could be regarded as the product of an artificial acceleration and refinement of strategies intrinsic to the immune system. PMID- 7776901 TI - Antihistamines, a possible risk factor for Alzheimer's disease. AB - Antihistamines are frequently administered to psychiatric patients for a variety of purposes. Several large studies of schizophrenics have revealed an extremely high prevalence of Alzheimer's disease neuropathology compared with that in the general population. The neuroleptic treatment of schizophrenia appears to be implicated in this phenomenon. Many of the neuroleptics have anticholinergic effects, some being antihistamines as well, including chlorpromazine. It is proposed here that anticholinergics, including many antihistamines, either exacerbate the Alzheimer process or possibly contribute to its etiology/pathogenesis through their effects on cerebral cholinergic systems. Parsimony in the use of antihistamines thus appears to be warranted both for non patients and schizophrenics pending the resolution of this issue. PMID- 7776900 TI - Meditation, melatonin and breast/prostate cancer: hypothesis and preliminary data. AB - The objective of this study was to test the hypothesis that the regular practice of mindfulness meditation is associated with increased physiological levels of melatonin. Melatonin may be related to a variety of biologic functions important in maintaining health and preventing disease, including breast and prostate cancer. Previous studies have shown melatonin production is photosensitive and we suggest here that it also may be psychosensitive. A cross-sectional study of 12 hour (20:00-08:00) urinary 6-sulphatoxymelatonin was conducted from which we analyzed data from 8 women who regularly meditate (RM) and 8 women who do not meditate (NM). All samples were collected in the homes of study participants. Volunteers were recruited to provide 12-hour overnight samples of urine. All subjects collected the samples on one night during the same 1-week period. There was no explicit intervention. However, all RM were either graduates of, or teachers in, the University of Massachusetts Stress Reduction and Relaxation Program. The main outcome measure was the total excretion of urinary 6 sulphatoxymelatonin. Multiple linear regression (Proc GLM in SAS) was performed to test the effect of meditation (RM vs NM) on 6-sulphatoxymelatonin. The results of the study were that after controlling for the non-significant effect of menstrual period interval, we found an effect of meditation group (RM vs NM: b = 1.983; F = 6.78; p = 0.02) and age (for each integer year: b = 0.169; F = 8.41; p = 0.01). The conclusion is that study results are consistent with our hypothesis and indicate that melatonin might be a useful parameter in testing similar psycho social interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776902 TI - The biology of deception: emotion and morphine. AB - The biology of deception suggests that denial-like processes are at the core of the cognitive coping. In this regard, with cognitive ability, one associates or assumes that this process occurs by way of a 'rational' mind. Such a detailed cognitive process as being rational would also lead, counter intuitively, to inactivity and or major delays in conclusion reaching. Thus, our perceived rationality may also be a deceptive behavioral response. Of equal noteworthyness, man is also 'emotional'. We surmise that emotion represents the pre-cognitive short-cut to overcome this potential for excessive rationality. In this light, we may explain certain psychiatric disorders such as obsessive-compulsive behavior as emotional extremes dealing with cognitive habits used to bind anxiety operating most probably at the pre-cognitive level. Given recent discoveries in neuroimmunology and an understanding of naturally occurring morphine as both an immune and neurological down-regulatory substance we hypothesize that abnormalities associated with emotional extremes may be due, in part, to morphinergic imbalances. PMID- 7776903 TI - Cultured human keratinocytes as a model for studying the dopamine metabolism in schizophrenia. AB - The dopamine hypothesis is the major etiological hypothesis of schizophrenia which proposes that enhanced central nervous system dopaminergic activity is the causative factor for this disease. The hypothesis remains unproven despite decades of research. The major difficulty in studying the disease is due to the unavailability of a suitable animal model. Studies with human blood, cerebrospinal fluid or post-mortem brains lead only to inconclusive results, due to the effects of medication and other environmental factors. No extra-neuronal cells, with the exception of adrenal medulla, have been reported to contain a dopamine metabolic pathway. Literature evidence and our own study suggest that human keratinocytes express the enzymes to synthesize and degrade dopamine. We have compared the properties of tyrosine hydroxylase, the rate-limiting enzyme, from mouse striatum and from human skin keratinocytes cultured in vitro. Moreover we could also detect dopamine beta hydroxylase and catechol-o-methyl transferase in keratinocytes. We propose that human keratinocytes cultured in vitro can be used to study the relevance of dopamine metabolism to schizophrenia under controlled conditions avoiding the effects of medication and other environmental factors. PMID- 7776905 TI - The role of mast cells and diet in the onset and maintenance of multiple sclerosis: a hypothesis. AB - Mast cells may invade the brain as a consequence of a childhood infection or predisposition, and it is proposed that multiple sclerosis arises due to the effect of various mediators (histamine and protease) released from the perivascular mast cells after stimulation by some diet factor. PMID- 7776904 TI - Neutrophil-macrophage interaction: a paradigm for chronic inflammation. AB - Autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease are characterized by chronic inflammatory responses resulting in tissue damage. These diseases have a number of common denominators including: abnormal cytokine expression, aberrant antigen-antibody complexes, T cell anomalies, and increased numbers of neutrophils and macrophages. We propose that the interaction between neutrophils and macrophages induces a state of chronic inflammation which contributes to the disease state. One of the central players in this scenario is myeloperoxidase (MyPo). This enzyme functions in the 'cytotoxic triad' and is involved in cell killing. Studies done by the present investigators have known that MyPo, which is released from neutrophils, induces macrophages to secrete interleukin-1, interferon alpha beta and tumor necrosis factor alpha. Furthermore, our studies have suggested a major immunoregulatory role of this enzyme. We propose that the release of MyPo from neutrophils and subsequent binding to macrophages initiates a cascade of events which enhance the production of reactive oxygen intermediates and cytokine expression resulting in the chronic inflammatory state associated with autoimmune diseases. PMID- 7776906 TI - Computers and the clinical laboratory. AB - Quality control in the clinical laboratory has long been an important concern. The techniques used for several decades have relied heavily on aggregated data analysis of the data within the clinical laboratory itself, techniques which were feasible even in a system of manually maintained laboratory records. The development of increasingly sophisticated computerized hospital information systems presents an opportunity to significantly expand upon traditional quality control efforts. PMID- 7776907 TI - Adaptation and cross-resistance: an explanation for the existence of different radiosensitivities among malignant melanoma cells. AB - A hypothesis is presented to explain the apparent difference in the radioresponsiveness of melanoma lesions whether they are located on the skin or in other parts of the body. The hypothesis states that the radiosensitivity of a cell may change when the cell adapts to live and grow in a different environment. The most important environmental factor that affects the radiosensitivity of cutaneous melanoma cells appears to be the partial pressure of oxygen in their immediate environment. By virtue of adapting to grow in an environment having a high partial pressure of oxygen, the melanoma cells located on the skin may have developed a better antioxidant defense mechanism than cells that metastasize to, and grow in, other parts of the body having lower partial pressures of oxygen such as lymph nodes, brain and viscera. Because some of the cell-damaging effects of both oxygen and ionizing radiation are mediated through a similar mechanism, the melanoma cells on the skin become cross-resistant to ionizing radiation because of their higher tolerance to oxygen toxicity. PMID- 7776908 TI - Reducing the toll of diabetic complications. PMID- 7776909 TI - Enterohaemorrhagic Escherichia coli: an emerging food-borne pathogen with serious consequences. PMID- 7776910 TI - Isolation of HIV-1 from experimentally contaminated multidose local anaesthetic vials. AB - OBJECTIVE: To investigate the hypothesis that HIV can be transmitted via contamination of multidose vials of local anaesthetic solution through reuse of needles and syringes. DESIGN AND SETTING: Laboratory study. (1) By experiments with multidose vials and disposable needles and syringes, we identified a sequence of events in which HIV could contaminate the anaesthetic solution. (2) Three anaesthetic solutions were contaminated with a laboratory strain of HIV and tested by viral culture and p24 enzyme immunoassay one, two and four hours later to see how long the virus remained active. RESULTS: (1) Needles and syringes retained small volumes of fluid after use (mean, 25 microL; in syringe alone, mean 16 microL) which could be transferred to multidose vials of local anaesthetic. (2) 10 mL of anaesthetic solution contaminated with 8 microL of HIV infected solution (equivalent to 1% infected lymphocytes in vivo) contained active virus one hour later. In some settings, HIV could be isolated four hours after exposure. CONCLUSION: When inadvertently contaminated with HIV, multidose solutions represent a potential source of transmissible virus. PMID- 7776911 TI - Screening for diabetic retinopathy. AB - OBJECTIVES: To identify factors associated with a high risk of diabetic retinopathy in order to rank patients for urgency of examination by fundal photography. DESIGN: Retrospective case survey. PATIENTS: Eight hundred and eighty-eight consecutive diabetic patients who were routinely referred for mydriatic fundal photography to the Queen Elizabeth Hospital, Adelaide, between August 1987 and May 1992. OUTCOME MEASURES: The prevalence of non-proliferative and proliferative diabetic retinopathy and patient biochemical and demographic characteristics and urinary albumin excretion rate. RESULTS: The prevalences of nonproliferative and proliferative diabetic retinopathy were 18.1% and 2.4%, respectively. Multiple logistic regression analysis established that treatment with insulin or oral hypoglycaemic drugs was associated with the highest risk of diabetic retinopathy (odds ratio [OR], 14.7; 95% confidence interval [CI], 3.4 63.2), while duration of diabetes > or = 7 years (OR, 3.6; CI, 1.9-6.8), age 50 66 years (OR, 2.1; 95% CI, 1.1-4.0) and albumin excretion rate > or = 21 micrograms/min (OR, 2.2; 95% CI, 1.1-4.5) were also significant risk factors. Non significant variables were hypertension, obesity and sex. CONCLUSIONS: Diabetic patients may be ranked for urgency of retinal photographic screening based on mode of treatment and duration of diabetes, thereby facilitating examination of patients at highest risk of asymptomatic diabetic retinopathy and increasing the efficiency of the screening program. PMID- 7776912 TI - Trends in prostate cancer incidence and mortality rates in South Australia, 1977 1993. AB - OBJECTIVE: To investigate trends in recorded incidence and mortality rates for prostate cancer in South Australia. DESIGN: A multiple Poisson regression analysis of recorded incidence (by diagnostic period) and mortality (by year of death), after adjusting for age at diagnosis and residential location. SUBJECTS AND SETTING: 8073 patients with prostate cancer and 2659 who died of prostate cancer as notified to the South Australian Cancer Registry for 1977-1993. MAIN OUTCOME MEASURES: The relative risk of a recorded diagnosis of prostate cancer (by period of diagnosis), and of a death from prostate cancer (by year of death). RESULTS: During 1977-1989, the recorded age-standardised incidence of prostate cancer was stable, but it increased markedly thereafter. The relative risk (95% confidence limits) of diagnosed prostate cancer was 1.36 (1.29, 1.43) in 1990 1992, and 2.26 (2.12, 2.42) in 1993, when compared with 1977-1989. There was a smaller and less certain increase in prostate cancer mortality. CONCLUSIONS: The large increase in recorded incidence of prostate cancer in South Australia is thought to be due mostly to increased disclosure of latent cases from increased clinical investigations. Until there is experimental evidence of health benefits from screening and related investigations for prostate cancer in asymptomatic men, it will be difficult to reconcile benefits with costs. PMID- 7776913 TI - Diet modification in lowering plasma cholesterol levels. A randomised trial of three types of intervention. AB - OBJECTIVE: To compare the efficacy of three types of diet and lifestyle interventions for lowering plasma lipid levels. DESIGN: Randomised parallel-group trial. SUBJECTS AND SETTING: Adults with plasma cholesterol levels of 5.5-8.0 mmol/L attending two Sydney community health screening clinics were asked to participate: 179 agreed and 131 completed the study. INTERVENTIONS: A pamphlet with brief advice; group dietary counselling; or individual counselling. Counselling included three sessions with a dietitian/nutritionist over six months. MAIN OUTCOME MEASURES: Plasma total cholesterol levels measured by Reflotron analyser; fasting serum lipid levels measured by standard laboratory methods; and calculated low-density lipoprotein cholesterol levels. RESULTS: Significantly lower plasma total cholesterol levels (Reflotron) were observed at two months and at six months with each of the three interventions. Additionally, both types of dietitian-based counselling resulted in small but significant decreases in plasma low-density lipoprotein cholesterol levels at six months in a subset of subjects. CONCLUSION: Although there were no statistically significant differences in efficacy between the three types of intervention, dietitians have a role to play in setting up such counselling programs. PMID- 7776915 TI - Prevention of suicide in old age. AB - The prevention of suicide in old age has received little attention, despite suicide rates being highest in older men. About 90% of older people who attempt or complete suicide have a mental disorder, usually depression, which often has been inadequately treated. Other treatable contributing factors include pain, grief, loneliness, alcoholism and carer stress. Few suicides in older people occur in the context of terminal illness or can be regarded as "rational". Educational programs are required to improve the recognition and treatment of depression in primary care. PMID- 7776914 TI - Confusion, cortical blindness and fever. PMID- 7776916 TI - Early detection of diabetic retinopathy. AB - Diabetic retinopathy remains a leading cause of blindness in Australia. Most cases can be prevented by timely laser photocoagulation and this requires early detection of asymptomatic retinopathy. The Australian Diabetes Society recommends regular retinal examinations through dilated pupils, either at diagnosis of diabetes (onset over 30 years), or five years after diagnosis (onset under 30 years). Examination should be repeated at least every two years, or more frequently in the presence of visual symptoms, pregnancy or other risk factors. Diabetic patients and primary care physicians should be better informed about the effectiveness of timely treatment of diabetic retinopathy and the need for regular eye examinations, either by general practitioners or through referral to ophthalmologists. PMID- 7776917 TI - Drugs and the kidney in the elderly. AB - The high rates of drug-induced acute renal failure, worsening chronic renal dysfunction and systemic toxicity of renally excreted drugs in the elderly can be minimised by carefully assessing renal function, avoiding potentially nephrotoxic drugs as much as possible and closely monitoring drug concentrations and renal function when they must be used. The co-existence of impaired renal function, degenerative vascular disease or cardiac failure in the elderly substantially increases the risk of renal toxicity. When in doubt about potential nephrotoxicity or an increased risk of systemic toxicity from renally excreted drugs in the elderly, the practitioner should consult the numerous published guidelines. PMID- 7776919 TI - Health outcomes: of means and ends. PMID- 7776918 TI - Theophylline. PMID- 7776920 TI - Health outcomes: of means and ends. PMID- 7776921 TI - Stereotypes of aboriginal health. PMID- 7776922 TI - Invasive pneumococcal disease in central Australia. PMID- 7776923 TI - An improved workers' compensation and rehabilitation certificate. PMID- 7776925 TI - Peptic disease: can we afford current management? PMID- 7776924 TI - Possible serotonin syndrome with moclobemide and pethidine. PMID- 7776926 TI - Chronic intractable focal epilepsy: a case report. PMID- 7776927 TI - Fatal intracranial haematomas in two patients with brown snake envenomation. PMID- 7776929 TI - Malaria acquired in Bali. PMID- 7776928 TI - BreastScreen services. PMID- 7776930 TI - Ophthalmomyiasis: a shot in the eye. PMID- 7776931 TI - Surviving in the house of God. PMID- 7776932 TI - [Wiesbaden 1995: Medical orientation and priorities]. PMID- 7776933 TI - [Duration of the effect of inhaled corticosteroids on lung function and sensitivity of the respiratory tract in patients with bronchial asthma]. AB - AIM: The effects of cessation of therapy with inhaled steroids on symptoms, lung function, and airway responsiveness in stable bronchial asthma should be examined. PATIENTS AND METHODS: During a 4-week run-in period 24 patients inhaled beclomethasone dipropionate (BDP) 2000 micrograms/d and salbutamol 800 micrograms/d. This was followed by a 6-week treatment period during which the patients obtained either placebo plus 800 micrograms salbutamol or 2000 micrograms BDP plus 800 micrograms salbutamol in a randomized double-blind design. Symptoms, lung function, and airway responsiveness to histamine were measured before and after the run-in period and at the end of each week during the treatment period. RESULTS: Airway responsiveness was assessed as the concentration of inhaled histamine which caused a 20% fall in FEV1 compared to baseline (PC20). During the run-in period, 21 of the 24 patients showed an increase of PC20 (p = 0.0005). In the placebo group, 5 patients had to cease the protocol after 1 to 4 weeks of the treatment period because of intolerable symptoms and severe worsening of lung function; PC20 on entry was significantly smaller in these patients compared to those who completed the protocol (p = 0.01). After 6 weeks, FEV1 had decreased by 8.5% (p = 0.005) and PC20 by 1.71 doubling concentrations (p = 0.0003). In the BDP group, all patients completed the study and PC20 after the treatment period was significantly higher (p = 0.04) in the BDP than in the placebo group. CONCLUSION: Our data suggest that patients on long-term inhaled steroid therapy with a high degree of bronchial hyperresponsiveness are more likely to show early deterioration of their clinical state after cessation of inhaled steroids. PMID- 7776934 TI - [Socioeconomic evaluation of the effect of rhDNase on the cost of treating infections of the respiratory tract in patients with cystic fibrosis]. AB - BACKGROUND: Data from a multicenter, placebo-controlled, double-blind, parallel clinical trial on the use of aerosolized recombinant human DNase (rhDNase), known as Pulmozyme produced by Genentech, about the treating of respiratory-tract infections among patients with cystic fibrosis (CF), has been used to evaluate possible economic effects by identifying the direct medical costs. To calculate the cost an intention-to-treat approach has been used. PATIENTS AND METHOD: The patients were randomly placed in one of three treatment groups. The first group was treated with a 2.5 mg dose of rhDNase and one dose of placebo daily, the second group with placebo twice a day. The third patient group (treated with a 2.5 mg dose of rhDNase twice a day) was not included in this study. RESULTS: The main measurements of resource utilization of services for treatment of respiratory-tract infections were the number of hospitalizations in the follow-up period of 24 weeks (0.41 rhDNase once daily, 0.56 placebo), the number of total days in hospital (4.9 rhDNase, 6.4 placebo), the number of total days of outpatient intravenous antibiotic therapy (2.9 rhDNase, 4.4 placebo), the number of total days of inpatient intravenous antibiotic therapy (4.8 rhDNase, 6.2 placebo), the number of total days of outpatient oral antibiotic therapy (23.5 rhDNase, 25.2 placebo) and the number of total days of inpatient oral antibiotic therapy (0.59 rhDNase, 0.55 placebo). From a health insurance perspective the total direct cost based on a weighted per diem for German CF-centres was 5,879 DM (rhDNase) vs 7,849 DM (placebo) per patient respectively. Costs of antibiotics were estimated using all available information on the consumption of antibiotic drugs revealing 2,954 DM per patient in the rhDNase-group and 4,213 DM in the placebo-group. The large cost differences remain also true in a sensitivity analysis introducing minima and maxima as key factors. CONCLUSION: As a result of this study we conclude that the use of rhDNase in treatment of respiratory-tract infections in patients with cystic fibrosis is cost saving and less burdened for the patients. However, all cost estimates do not include the cost of rhDNase itself, which are DM 9,094 for the period of follow-up. PMID- 7776935 TI - [Traumatically-induced ischemia of the hands]. AB - BACKGROUND: The widely unknown hypothenar hammer syndrome (HHS) is caused by chronic mechanical trauma; in these cases the hypothenar is used as a tool. This may cause intimal lesions of the ulnar artery usually near the hamate bone resulting in thrombosis or aneurysms. PATIENTS: Six patients with HHS are presented. In four cases occupational activities were most probable cause for HHS, in two patients sport activities. DIAGNOSIS: Clinical examination already indicates insufficient blood supply in the supply area of the ulnar artery. Non invasive methods of examination are doppler measurements of hand arteries and occlusion plethysmography of finger arteries. For differential diagnosis capillaroscopy, laboratory tests and hand arteriography can be necessary. THERAPY: Avoiding the releasing cause is main part in therapy of HHS. Only in few patients special medical treatment is indicated. CONCLUSION: Positive evidence of causal relationship between occupational exposure and appearance of HHS has to be acknowledged as occupational disease. PMID- 7776936 TI - [Therapy of tuberculosis in the adult]. PMID- 7776937 TI - [Rheumatology update--1. Summary of clinically significant current knowledge and outlook perspective of relevant trends in etiopathogenetic research, diagnostic methods and therapeutic possibilities]. PMID- 7776938 TI - [Torsade de pointes and QT syndrome]. PMID- 7776940 TI - [God in the medical dialogue. Dialogue of the God-less?]. PMID- 7776939 TI - [Asthma is asthma, is asthma...]. PMID- 7776941 TI - [Meningoencephalitis caused by Listeria monocytogenes in excessive ultraviolet light irradiation in the whole-body solarium]. PMID- 7776942 TI - [Toxic hydrocarbon pneumonitis in a "fire eater"]. PMID- 7776943 TI - Reinventing the American hospital. AB - The American hospital is being reinvented to conform with the forces that are replacing the acute, inpatient-oriented illness model of health care with a disease-prevention, health-promotion, primary-care one. Although hospitals will no longer conduct the "core business" of American health care, they can play a key role by empowering others and facilitating the integration of health services across the continuum of care. New management and governance structures will be required, as will population-based health status needs assessments, new relations with physicians, re-engineering of the clinical processes, organization-wide commitment to improving quality, information systems that link patients and providers, and creation of an overall community care management system. Despite major barriers, there are examples of progress. PMID- 7776944 TI - Expanding the home care concept: blurring distinctions among home care, institutional care, and other long-term-care services. AB - Distinctions between home care and residentially based care are blurring because of two trends: home care providers are offering services, including personal assistance, outside of the private, self-contained family home or apartment; and a market-driven movement is underway to develop group residential settings where long-term-care (LTC) consumers with substantial disability receive personal care and nursing in their own, fully equipped, apartments where they largely control the schedule. For the customers, such boundary blurring can lead to experiences of greater power and normality in their everyday lives. State regulations will help determine the extent to which new, "residentially" oriented models of LTC are feasible. Home care providers are challenged to develop flexible and creative paradigms for service that are built on a recognition that older adults with disabilities have the right to choose risks. PMID- 7776945 TI - "Man, woman, and chore boy": transformations in the antagonistic demands of work and care on women in the nineteenth and twentieth centuries. AB - Because the population is aging when increasing numbers of women are entering the labor force, policy makers stress the problems of reconciling the conflict between work and care. This conflict has a long history, especially for poor women and women of color. During the nineteenth century, caregiving was more likely to clash with domestic work than with paid employment. The expansion of the health care delivery system between 1890 and 1940 removed some responsibilities from the home. But rather than disappearing, many caregiving obligations changed. The growth of women's labor force participation altered the relation between work and care. Some women quit jobs they desperately needed when family members fell ill. Others left serious sick or disabled family members unattended. PMID- 7776946 TI - Toward allocative efficiency in the prescription drug industry. AB - Traditionally, monopoly power in the pharmaceutical industry has been measured by profits. An alternative method estimates the deadweight loss of consumer surplus associated with the exercise of monopoly power. Although upper and lower bound estimates for this inefficiency are far apart, they at least suggest a dramatically greater welfare loss than measures of industry profitability would imply. A proposed system would have the U.S. government employing its power of eminent domain to "take" and distribute pharmaceutical patents, providing as "just compensation" the present value of the patent's expected future monopoly profits. Given the allocative inefficiency of raising taxes to pay for the program, the impact of the proposal on allocative efficiency would be at least as good at our lower bound estimate of monopoly costs while substantially improving efficiency at or near our upper bound estimate. PMID- 7776947 TI - Rare diseases, drug development, and AIDS: the impact of the Orphan Drug Act. AB - The Orphan Drug Act provides public subsidies and incentives to spur the development of drugs for rare diseases--drugs that the private sector might otherwise consider unprofitable to produce. Although the act has achieved numerous successes, the high prices and extraordinary sales generated by some orphan drugs lead to a pivotal policy question: how can the act be used to meet the legislative goal of stimulating drug development for small patient populations without resulting in prices that make drugs inaccessible? This question is explored using the example of AIDS drugs, many of which received subsidies under the act, to illustrate central points. The history of the act, its weaknesses, and strategies for reform are described as well. PMID- 7776948 TI - The illusion of failure: trends in the self-reported health of the U.S. elderly. AB - Data from the National Health Interview Survey showed a trend toward worsening self-reported health among older American men and women during the 1970s. This evidence--combined with the significant declines in age-specific mortality observed since the 1960s--led some researchers to suggest that the health of the older population is declining. An examination of recent trends in self-reported health indicates that the health declines observed during the 1970s generally reversed during the 1980s. This reversal not only belies the argument that lower adult mortality implies worse health, but also challenges the belief that trends in self-reported health during the 1970s reflected actual health declines. A more plausible explanation is that changes in the social and economic forces, combined with earlier diagnosis of preexisting conditions, influenced the options available for responding to health problems. PMID- 7776949 TI - Serious eye injuries associated with fireworks--United States, 1990-1994. AB - Eye injuries caused by fireworks are often severe and can cause permanently reduced visual acuity or blindness. Findings from the National Electronic Injury Surveillance System database maintained by the U.S. Consumer Product Safety Commission (CPSC) indicate that approximately 12,000 persons are treated each year in U.S. emergency departments because of fireworks-related injuries; of these, an estimated 20% are eye injuries. To improve characterization of fireworks-related eye injuries, data were analyzed from the United States Eye Injury Registry (USEIR) for July 1990-December 1994 and from the Eye Injury Registry of Alabama (EIRA) for August 1982-July 1989. This report summarizes the findings of these analyses. PMID- 7776950 TI - Achievement of dietary goals--Kansas, 1993. AB - Fat intake and other dietary factors are associated with increased risk for important chronic diseases, including cardiovascular disease and cancer (1-4). To characterize the nutritional behaviors of residents of Kansas, the Kansas Department of Health and Environment (KDHE) conducted a nutrition assessment survey in 1993 and has used the results as a baseline for monitoring progress toward attaining Healthy Kansans 2000 (HK2000) nutrition objectives. This report summarizes selected findings from the nutrition survey relative to three HK2000 objectives: 1) increase to 35% the proportion of adults who consume five or more daily servings of fruits and vegetables; 2) increase to 40% the proportion of adults whose dietary fat intake constitutes < 30% of their total food-energy intake (a lower fat diet); and 3) increase to 70% the proportion of adults who consume > or = 600 mg of calcium daily (75% of the Recommended Dietary Allowance for adults aged > or = 25 years [5]). PMID- 7776951 TI - Lyme disease--United States, 1994. AB - For surveillance purposes, Lyme disease (LD) is defined as the presence of an erythema migrans rash > or = 5 cm in diameter or laboratory confirmation of infection with Borrelia burgdorferi and at least one objective sign of musculoskeletal, neurologic, or cardiovascular disease (1). In 1982, CDC initiated surveillance for LD, and in 1990, the Council of State and Territorial Epidemiologists adopted a resolution that designated LD a nationally notifiable disease. This report summarizes surveillance data for LD in the United States during 1994. PMID- 7776952 TI - African pygmy hedgehog-associated salmonellosis--Washington, 1994. AB - During 1994, the Washington Department of Health Public Health Laboratory reported the isolation from a human of a rare Salmonella serotype, Salmonella serotype Tilene. This report summarizes the epidemiologic investigation of the case by the Seattle-King County Department of Public Health, which suggested the infection was related to exposure to African pygmy hedgehogs. PMID- 7776954 TI - Evidence for aestivation specific proteins in Otala lactea. AB - Changes in [35S]methionine protein labeling patterns were examined by following incorporation into the acid precipitate protein fraction of land snails, Otala lactea (Muller) (Pulmonata, Helicidae). Labeled proteins were analyzed by SDS polyacrylamide gel electrophoresis and isoelectric focusing columns. Snails in four different physiological states were compared: active controls, short term aestivating snails (injected and allowed to enter aestivation), long term aestivating snails (aestivated for 14 days, injected, and maintained in the aestivating state), and snails aroused after aestivation (aestivated, injected, and aroused). Protein associated radioactivity was measured over a 7 day time course post injection. Autoradiographic analysis of SDS-polyacrylamide gels showed increases in the radioactivity of four proteins: 91 kDa (hepatopancreas, day 1 in long term aestivating animals), 50 kDa (hepatopancreas, day 2 in short term aestivating snails), 70 kDa and 30 kDa (foot, day 2 in short term aestivating animals). Hepatopancreas and foot from day 1 long term aestivating and day 2 short term aestivating animals were also analyzed by isoelectric focusing columns. Several pH-specific differences were apparent when controls and aestivating animals were analyzed. In particular a peak of radioactivity was observed at pH 5.05 in 1 d long term aestivating hepatopancreas and at pH 4.30 in 2d short term aestivating animals. Several differences were noted in foot with no specific pattern emerging. SDS-polyacrylamide gel electrophoresis analysis of the hepatopancreas peaks showed the appearance of several bands with increased radioactivity, including the 91 kDa and 50 kDa proteins described above. These results suggest that O. lactea aestivation specific proteins may be involved in the transition to a depressed metabolic state. PMID- 7776953 TI - Cellular hypertrophy in cardiomyopathic patients is associated with lower creatine-stimulated mitochondrial respiration. AB - The mitochondrial respiration rate and morphometric indices in endomyocardial biopsy samples were measured in 43 patients with dilated cardiomyopathy selected in accordance to WHO criteria by endomyocardial biopsy studies after excluding of various forms of myocarditis, alcoholic cardiomyopathy and other specific diseases of the heart. A group of 13 patients with unusually high mean myocyte diameter, 30 +/- 4 microns, and nuclear size, 57 +/- 5 microns, was selected. The remainder of patients (n = 30) had significantly lower mean myocyte diameter and nuclear size, 23 +/- 3 and 42 +/- 6 microns, respectively, (p < 0.01). Creatine stimulated elevation in mitochondrial respiration rate as measured in saponin skinned fibers was found in the former group to be much lower (36 +/- 4%) as compared with the remainder (90 +/- 12%). Also, the former group of patients had higher left ventricular enddiastolic pressure and volume index with concomitantly decreased ejection fraction. The results indicate that marked nuclear and cellular hypertrophy is associated with lower creatine-stimulated mitochondrial respiration rate and more severe cardiac failure. They suggest that disorders in energy supply to myofibrils may be related to disturbances in cellular genetic apparatus. PMID- 7776955 TI - Ribosomal proteins of Thermomyces lanuginosus--characterisation by two dimensional gel electrophoresis and differential disassembly. AB - One- and two-dimensional gel electrophoresis were employed to characterise the proteins derived from the ribosomes of the thermophilic fungus Thermomyces lanuginosus. Approximately 32 (29 basic and 3 acidic) and 45 (43 basic and 2 acidic) protein spots were resolved from Th. lanuginosus small and large ribosomal subunits, respectively. The molecular weight of the small subunit proteins ranged from 9,800-36,000 Da with a number average molecular weight of 20,300 Da. The molecular weight range for the large subunit proteins was 12,000 48,500 Da with a number average molecular weight of 25,900 Da. Most proteins appeared to be present in unimolar amounts. These data are comparable with but not identical to those from other eukaryotic ribosomes. The sensitivities of the ribosomal proteins to increasing concentrations of NH4Cl were also evaluated by two-dimensional gel electrophoresis. Most ribosomal proteins were gradually released over a wide range of salt concentrations but some were preferentially enriched in one or two salt conditions. PMID- 7776956 TI - Damage to cultured lens epithelial cells of squirrels and rabbits by UV-A (99.9%) plus UV-B (0.1%) radiation and alpha tocopherol protection. AB - The purpose of this research is to observe the near-UV radiation induced damage to cultured rabbit and squirrel lens epithelial cells as related to destruction and alterations of specific biochemical targets in the cells and to determine protective effects on the cells and targets that are provided by alpha tocopherol. Confluent monolayers of cultured rabbit and squirrel lens epithelial cells were exposed to black light (BL) lamps, which emit predominantly UV-A radiation. These cells received a mixture 3 J/cm2 of UV-A and 4 mJ/cm2 of UV-B per h. This mixture is termed near UVA (i.e.: predominantly UV-A). Cells were exposed in Tyrode's or in MEM without or with alpha-tocopherol added at 2.5-10 micrograms/ml. Analyses of cell viability and survival, the physical state of cytoskeletal actin, and the activities of Na-K-ATPase and catalase were made. Exposure to near UVA damaged these cells as measured by vital staining and colony forming ability. Pretreatment with alpha-tocopherol decreased the magnitude of near UVA cytotoxicity. Near UVA exposure in MEM always produced more damage to the cells and biochemical targets than in Tyrode's. Cytoskeletal actin was degraded and the activities of Na-K-ATPase and catalase were markedly inhibited by UV-exposure. All of these targets were at least partially protected by alpha tocopherol in the medium. Without alpha-tocopherol added to the media, the viability and survival of the cells did not recover even after 25 h of incubation. Cell viability was better protected from near UVA by alpha-tocopherol than was the ability to grow into colonies. This indicates that alpha-tocopherol protects actin, catalase, and Na-K-ATPase from near UVA damage. PMID- 7776957 TI - Regulation of argininosuccinate synthetase level by corticosteroid and pancreatic hormones during perinatal period. AB - The urea cycle takes place in the hepatocyte of ureothelic animals. The conversion of ammonia into urea involves five reactions. The first 2 take place in the matrix of the mitochondria, the last 2 occur in the cytosol. Argininosuccinate synthetase (AS) is the third reaction of the urea cycle. It catalyses the condensation of citrulline and aspartate into argininosuccinate. We have previously reported that rat AS activity was present in the cytosol and the outer membrane of the mitochondria. We have shown that, at the activity level, the colocation of AS was changing during fetal and neonatal development and was under the control of corticosteroid and pancreatic hormones. However, an unresolved issue was whether both AS had the same specific activity and that their location was changing during ontogenesis or that the specific activities of mitochondrial and cytosolic enzymes were different and/or modified during this period. In the present report, we compared the compartmentalization of AS activity and protein level in the fetus, the new-born and the adult rat and the role of corticosteroid and pancreatic hormones. Specific activities of both AS remained unchanged during ontogenesis. Glucocorticoids induced an increase in mitochondrial AS while glucagon appeared to induce a concomitant decrease in the level of mitochondrial AS and an increase in cytosolic AS. PMID- 7776958 TI - Calcium administration increases calcium-binding protein regucalcin concentration in the liver of rats. AB - The alteration of regucalcin concentrations in the liver and serum of rats administered orally calcium is investigated. Rats received a single oral administration of calcium chloride solution (25, 50 and 75 mg Ca/100 g body weight). The administration of calcium (50 mg/100 g) produced a significant increase in liver regucalcin concentration between 30 and 180 min after the administration, while serum regucalcin concentration was not altered appreciably. The effect of calcium administration increasing liver regucalcin concentration was also seen with the dose of 25 mg/100 g. When liver cytosol prepared from normal rats was incubated for 6 h in the presence of 10 microM Ca2+, the cytosolic regucalcin concentration at 3 and 6 h of incubation was decreased about 20% (p < 0.05) as compared with the value at zero time point, indicating that the presence of Ca2+ does not inhibit the decomposition of liver cytosolic regucalcin. Moreover, serum regucalcin concentration was not significantly altered by the incubation for 6 h at 37 degrees C, indicating a stability of regucalcin in rat serum. This suggests that the calcium administration-induced in liver regucalcin concentration is not based on the inhibition of regucalcin release from liver to serum. The present study demonstrates that regucalcin in the liver is clearly increased by calcium administration, presumably due to stimulating the protein synthesis. PMID- 7776959 TI - Production of native creatine kinase B in insect cells using a baculovirus expression vector. AB - A full-length human creatine kinase B (B-CK) cDNA was used to produce a recombinant baculovirus (AcDZ1-BCK). Sf9 cells infected with this recombinant expressed a homodimeric protein composed of 43 kDa subunits which, under optimal conditions, formed up to 30% of the total soluble cellular protein. Upon analysis by PAGE, zymogram assay and gel filtration chromatography the recombinant protein behaved like authentic dimeric human BB-CK protein. Studies with a newly produced monoclonal antibody (CK-BYK/21E10) directed against an epitope in the N-terminus of the protein confirmed the identity of the product. The recombinant BB-CK protein was purified to over 99% homogeneity from the total protein extract of AcDZ1-CKB infected cells in one single step involving anion exchange column chromatography on MonoQ in FPLC. Dialysed protein had a specific activity of 239 U/mg protein. PMID- 7776960 TI - Specific species and tissue differences for the gene expression of calcium binding protein regucalcin. AB - The existence and expression of gene encoding the Ca(2+)-binding protein regucalcin in various species and tissues were investigated with Southern and Northern hybridization analyses using regucalcin cDNA (0.9 kb of open reading frame). Genomic Southern hybridization analysis demonstrated that regucalcin gene was widely conserved among higher animals including human, monkey, rat, mouse, dog, bovine, rabbit and chicken. The gene was not found in yeast. The Northern blot analysis of poly (A) +RNAs extracted from the liver of various species showed that regucalcin mRNA was predominantly expressed in rat and mouse, although the expression was also seen in human, bovine and chicken. Furthermore, the enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG indicated that hepatic regucalcin concentration was most pronounced in rat as compared with that of guinea pig, mouse and chicken. These observations show that the gene expression of regucalcin and its protein synthesis is unique in the liver of rats, suggesting the existence of a specific mechanism in demonstrating regucalcin synthesis from gene. PMID- 7776961 TI - Protein phosphorylation patterns during aestivation in the land snail Otala lactea. AB - Protein phosphorylation patterns were investigated in whole tissues and subcellular fractions of active and aestivating Otala lactea (Muller) (Pulmonata, Helicidae). Measurement of overall protein phosphorylation showed that incorporation of 32P increased until the second day after injection and remained constant for the remaining 4 days of the time course. Comparison of tissues from aestivating and active snails on day 3 showed a decreased protein phosphorylation in aestivating snails (44% of active). No differences in total and protein associated radioactivity for foot, mantle or haemolymph were observed. Subcellular fractionation of the hepatopancreas localized the changes to plasma membrane, microsomal, and cytosolic fractions: values for aestivating animals were reduced to 71, 37 and 58% of the corresponding active values. Separation of the individual subcellular fractions on isoelectric focusing columns revealed differences in the phosphate incorporation patterns. Plasma membrane from aestivating animal hepatopancreas had a lower overall level of incorporation and fewer radioactive peaks in the pH 7-10 region than did the plasma membrane fraction from active animals. SDS-PAGE analysis of plasma membrane fractions from active and aestivating snails showed a relative decrease in phosphorylation between 60-80 kDa and 30-40 kDa. IEF analysis of cytosolic proteins from aestivating snail hepatopancreas also showed peaks of radioactivity that were apparently shifted by 0.3 pH units toward higher pI values. Increased phosphate incorporation was observed at a peak that corresponded to the pI value for pyruvate kinase in aestivating snails but definite assignment of peaks was not possible. SDS-PAGE analysis of cytosolic proteins showed an aestivation-related decrease in relative protein phosphorylation between 30-35 kDa and 40-45 kDa. A relative increase in phosphorylation during aestivation was observed for proteins between 16-22 kDa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776963 TI - Basic fibroblast growth factor stimulates connexin-43 expression and intercellular communication of cardiac fibroblasts. AB - Gap junctions (GJ) are membrane specializations responsible for intercellular communication and for ensuring electrical and/or metabolic coupling between cells. They are composed of connexins, a family of related proteins. Connexin-43 (Cx43) is a major connexin of the rat heart, expressed by myocytes as well as non muscle cells. In this communication we have examined expression of Cx43 by cardiac fibroblasts and regulation of its expression by an endogenous mitogen, basic fibroblast growth factor (bFGF). Recombinant human bFGF, administered to cultured cells which had been maintained in 0.5% serum for 48 h, induced dose dependent and statistically significant increases in Cx43 mRNA as well as protein accumulation, at 6 h after addition. Intercellular communication was also increased at 6 h but not 30 min after bFGF treatment, as assessed using a scrape loading protocol. It is concluded that the bFGF-induced stimulation of Cx43 expression caused increased coupling between cardiac fibroblasts. This would be of importance in injured myocardium, the increased bFGF content of which might stimulate electrical coupling involving fibroblasts of the scar tissue. PMID- 7776962 TI - Glycated albumin modified by Amadori adducts modulates aortic endothelial cell biology. AB - Increased protein glycation has been mechanistically linked to accelerated vascular pathobiology in diabetes. To test the influence of protein modified by Amadori glucose adducts on vascular cell biology, we examined the effect of glycated albumin on replicative capacity and basement membrane collagen production by aortic endothelial cells in culture. Relative to carbohydrate-free albumin, which supported cell proliferation and Type IV collagen synthesis, glycated albumin significantly inhibited 3H-thymidine incorporation and Type IV collagen production. The glycated albumin-induced effects were prevented by monoclonal antibodies (A717) that specifically react with Amadori-modified albumin, but not by IgG that was unreactive with glycated albumin. A717 had no effect on thymidine incorporation or collagen synthesis by cells cultured in the presence of nonglycated albumin. The findings indicate that the interaction of glycated albumin with endothelial cells, which have been shown to display dose responsive, saturable receptors, limits cell replication and triggers maladaptive biosynthetic programs, which may contribute to degenerative macrovascular disease in diabetes. PMID- 7776964 TI - The lutropin/choriogonadotropin receptor is palmitoylated at intracellular cysteine residues. AB - Most members of the family of G protein-coupled receptors have one or more conserved cysteine residues in their carboxy-terminal cytoplasmic tails which are believed to be consensus sites for palmitoylation. Indeed, a growing number of G protein-coupled receptors (rhodopsin, beta 2-, and alpha 2-adrenergic receptors) have now been shown to have palmitic acid covalently attached to this position. In the case of the beta 2-adrenergic receptor, it was also reported that mutation of the palmitoylated cysteine to glycine greatly diminished the ability of this receptor to interact with and activate Gs. Mutation of this conserved cysteine appears to have little or no effect on the ability of other members of this receptor family (rhodopsin, alpha 2-adrenergic and M2 muscarinic) to activate their cognate G proteins, however. The studies presented here were designed to determine whether another Gs-coupled receptor, the LH/CG receptor, is palmitoylated, and whether this modification is important for receptor function. To facilitate biochemical analysis, we examined these issues using cell lines stably transfected with the wild type LH/CG receptor (LHR-wt) or with a mutant receptor in which the two conserved cysteins were mutated to alanines (designated LHR-C621,622A). Our results show that LHR-wt is palmitoylated but that LHR C621,622A is not. We also show that LHR-C621,622A is capable of binding human CG (hCG) and transducing the cAMP signal. The main difference that we detected between the wild type and mutant receptor is that the latter is trapped intracellularly and does not appear to mature into the 85 kilodalton protein previously identified as the mature cell surface LH/CG receptor. PMID- 7776965 TI - Human chorionic gonadotropin (CG)- and phorbol ester-stimulated phosphorylation of the luteinizing hormone/CG receptor maps to serines 635, 639, 649, and 652 in the C-terminal cytoplasmic tail. AB - In a number of instances, binding of a ligand to its receptor results in receptor phosphorylation that mediates receptor uncoupling from its effector. Recently, we showed that human CG (hCG)- or phorbol ester- [phorbol 12-myristate-13-acetate (PMA)] stimulation of cells transfected with the LH/CG receptor induced rapid LH/CG receptor phosphorylation and a reduced cAMP response upon reexposure to hCG. The fact that hCG and PMA both phosphorylate and uncouple the LH/CG receptor suggests a common mechanism of action, namely the activation of protein kinase C. The studies presented here were designed to investigate the role of the C kinase in LH/CG receptor phosphorylation and to locate the phosphorylation site(s) within the receptor protein. The experiments presented here show that although hCG activates the C kinase in these cells, phosphorylation of the LH/CG receptor in response to hCG is maintained in C kinase-deficient cells. This suggests that activation of protein kinase C is not required for hCG-induced phosphorylation of its receptor. As a first step in locating the phosphorylation sites within the receptor polypeptide, we performed phosphoamino acid analysis of the phosphorylated LH/CG receptor. Only phosphoserine residues were detected. Based on the assumption that the phosphoserine(s) must be located within the intracellular regions of the receptor, we isolated cell lines expressing the wild type LH/CG receptor or receptors with cytoplasmic tails truncated at residue 653 or 631.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776966 TI - Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function. AB - The FSH receptor (FSHR) contains a large extracellular domain in which exist three potential sites for N-linked glycosylation. A truncated form of the FSHR representing only the extracellular domain was created and expressed in mammalian cells. We show that this truncated receptor is glycosylated, through the carbohydrates are not as fully processed as those of the full-length receptor. This truncated receptor, which remains intracellular, binds FSH with an affinity comparable to that of the full-length FSHR. Therefore, although other regions of the FSHR may contribute to hormone binding, the extracellular domain alone can confer high affinity binding. The above results suggest that N-linked FSHR carbohydrates may, in some way, be required for FSH binding. Therefore, further experiments, done in the context of the full-length receptor, were performed to determine the actual sites of glycosylation in the FSHR as well as to elucidate their role in the functions of the FSHR. Site-directed mutagenesis was done to individually or collectively disrupt the potential sites for N-linked glycosylation. Western blot analyses of the wild type vs. mutant receptors demonstrate that, of the three potential sites for N-linked glycosylation, Asn's 174 and 276 are actually glycosylated. Binding assays demonstrate that these two N-linked FSHR carbohydrates are redundant in function since carbohydrate at either Asn174 or Asn276 allows the receptor to be expressed on the cell surface and to bind FSH with normal affinity. However, FSH binding activity is not observed with nonglycosylated mutant receptors where both sites have been collectively disrupted. Similarly, when cells expressing the wild type FSHR were treated with tunicamycin to prevent N-linked glycosylation, the resulting nonglycosylated FSHR was not able to bind FSH. In contrast, normal high affinity binding of FSH was maintained when N-linked carbohydrates were enzymatically removed from wild type receptors. Our results demonstrate that while N-linked carbohydrates on the FSH receptor are not required directly for the binding of hormone, a carbohydrate at either Asn174 or Asn276 is required for the efficient folding of the nascent receptor protein into a conformation that allows high affinity binding of hormone. PMID- 7776968 TI - E1a activation of insulin receptor gene expression is mediated by Sp1-binding sites. AB - E1a adenoviral oncoproteins have been known to modulate genes important for the growth and differentiation of cells. Our laboratory is interested in understanding how insulin promotes the growth and proliferation of cells. In this report, we have examined the ability of E1a to modulate the insulin receptor gene expression. In HepG2 cells, expression of the 243-amino acid E1a protein stimulated expression of the chloramphenicol acetyltransferase reporter under the control of the insulin receptor promoter. 5'-Deletion analysis of the insulin receptor promoter indicated that the region between -630 and -607 is important for regulation by E1a. This region contains two GA and four overlapping GC boxes that are putative Sp1-binding sites. A DNA fragment containing these sites was used as a probe in gel retardation assays. Three specific protein-DNA complexes were detected with HepG2 nuclear extract. These complexes could be competed partially by the DNA fragments with mutations in either the GA or GC boxes, but not by the DNA fragment with a mutation in both the GA and GC boxes. In addition, mutation of each of these sites lowered the basal activity of the promoter and partially reduced transactivation by E1a. Simultaneous mutation in both GA and GC boxes further reduced the basal activity and abrogated transactivation by E1a. Taken together, these results indicate that the loss of binding ability of Sp1 (or Sp1-like factors) is concomitant with reduction of the basal activity and the loss of E1a inducibility of the gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7776967 TI - In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3. AB - The mechanisms by which GH regulates gene expression to alter growth and metabolism are unknown. We have demonstrated previously that in vivo GH treatment rapidly stimulates the tyrosine phosphorylation of multiple nuclear proteins and have identified the inducible transcription factor Stat1 (formerly Stat91) as one of the major GH-activated nuclear phosphoproteins. We now show that Stat3, a new member of the STAT (signal transducer and activator of transcription) family of transcription factors, is also phosphorylated on tyrosine residues and rapidly appears in the nucleus in response to GH. Activated Stat3 interacts with the naturally occurring c-sis-inducible element of the c-fos gene after GH treatment, as demonstrated by gel mobility shift assay, and is a component of gel-shifted bands A and B when the high affinity sis-inducible element is used as a probe. Our results suggest that multiple STAT proteins may mediate some of the pleiotropic effects of GH on gene expression. PMID- 7776970 TI - Induction of interferon-beta gene expression by dexamethasone in murine L929 cells. AB - Glucocorticoids bind to their receptors and trigger the transcriptional activation or repression of target genes by binding to DNA sequences, the glucocorticoid responsive element (GRE). The murine interferon-beta (Mu-IFN beta) gene in L929 cells can be induced by dexamethasone to give both transcription and translation products specific to murine IFN beta. The 3'-noncoding region of the Mu-IFN beta gene was found to contain a GRE very similar to the consensus GRE sequence involved in glucocorticoid-regulated genes. Gel retardation assays showed that the oligonucleotide corresponding to that GRE competed with the MMTV GRE oligonucleotide for glucocorticoid receptor binding and was supershifted by human antiglucocorticoid receptor antibodies. Transiently transfected murine cells (L929) with the GRE-IFN beta 3' sequence inserted upstream of the thymidine kinase promoter and the chloramphenicol acetyl transferase gene treated with dexamethasone with or without the antiglucocorticoid RU486 and their chloramphenicol acetyl transferase activity assayed, show that this GRE is efficient. We conclude that the Mu-IFN beta gene in L929 murine cells can be induced by dexamethasone, and that the hormone effect may be mediated by the 3' GRE sequence. PMID- 7776969 TI - c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-beta in osteoblastic cells. AB - We investigated the contribution of c-fos protooncogene in the mitogenic effect of transforming growth factor-beta (TGF beta) in serum-deprived, confluent rat calvaria osteoblastic cells. The TGF beta-induced growth in these cells was associated with an immediate and transient c-fos mRNA accumulation, similar to the inductive effect of fetal calf serum. To assess the role of c-fos in the response to TGF beta, we used a c-fos antisense (AS) oligonucleotide displaying duplex formation with rat c-fos mRNA. Studies of AS and sense (S) uptake by osteoblastic cells demonstrated that incorporation of labeled oligomers was maximal at 2 h, and the incorporated AS oligonucleotide remained intact for 24 h. Immunofluorescence analysis of c-Fos-labeled cells demonstrated that AS, but not S, oligonucleotide reduced c-Fos protein expression, suggesting specific efficient inhibition of c-fos translation by the AS oligomer. Proliferation assays showed that cell growth induced by fetal calf serum was inhibited by the AS, but not by the S oligonucleotide, in both normal rat osteoblasts and ROS 17/2.8 osteosarcoma cells, demonstrating efficient and specific blockage of cell growth by the AS oligomer. The mitogenic effect of TGF-beta was abolished in cells cultured in the presence of AS, whereas S had no effect, showing that c-fos is required for TGF beta-induced osteoblast cell growth. The results show that the induction of c-fos is implicated in the mitogenic effect of TGF beta in osteoblastic cells and provide a cellular mechanism involved in the response of these cells to TGF beta. PMID- 7776971 TI - Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. AB - The molecular basis for the different physiological effects of testosterone (T) and dihydrotestosterone (DHT) was investigated using recombinantly expressed wild type and mutant androgen receptor (AR). Rates of androgen dissociation from nuclear and cytoplasmic AR were compared with hormone- and concentration dependent receptor degradation rates. T dissociates from AR 3 times faster than DHT or methyltrienolone (R1881) and is less effective in stabilizing the receptor. Analysis of AR deletion mutants and AR/glucocorticoid receptor chimeras indicates that the AR NH2-terminal domain has a specific role in stabilizing the receptor by slowing the rate of ligand dissociation and AR degradation. Amino acid mutations that abolish receptor dimerization, nuclear localization, or DNA binding activity have no significant effect on androgen dissociation or AR degradation. A naturally occurring steroid-binding domain mutation (Val889 to Met) that causes androgen insensitivity, but does not alter equilibrium androgen binding affinity, lowered the androgen-binding capacity as a result of increased rates of androgen dissociation and AR degradation. Thus, AR stabilization and function require prolonged receptor occupancy with androgen, with a similar extent of stabilization observed at higher concentrations of faster dissociating androgens and lower concentrations of slower dissociating androgens. Retention of receptor-bound androgen is enhanced by an interaction between the AR NH2-terminal and steroid-binding domains. The ligand specificity and concentration dependence of receptor stabilization provide an explanation for physiological differences in the actions of T and DHT. PMID- 7776972 TI - Functional interactions of peroxisome proliferator-activated receptor, retinoid-X receptor, and Sp1 in the transcriptional regulation of the acyl-coenzyme-A oxidase promoter. AB - Peroxisome proliferator-activated receptor (PPARs) are members of the nuclear receptor superfamily. For transcriptional activation of their target genes, PPARs heterodimerize with the retinoid-X receptor (RXR). The convergence of the PPAR and RXR signaling pathways has been shown to have an important function in lipid metabolism. The promoter of the gene encoding the acyl-coenzyme-A oxidase (ACO), the rate-limiting enzyme in peroxisomal beta-oxidation of fatty acids, is a target site of PPAR action. In this study, we examined the role and the contribution of both cis-and trans-acting factors in the transcriptional regulation of this gene using transient transfections in insect cells. We identified several functional cis-acting elements present in the promoter of the ACO gene and established that PPAR-dependent as well as PPAR-independent mechanisms can activate the ACO promoter in these cells. We show that the PPAR/RXR heterodimer exerts its effect through two response elements within the ACO promoter, in synergy with the transcription factor Sp1 via five Sp1-binding sites. Furthermore, this functional interaction also occurs when Sp1 is co expressed with PPAR or RXR alone, indicating that activation can occur independently of PPAR/RXR heterodimers. PMID- 7776973 TI - Ligand occupancy is not required for vitamin D receptor and retinoid receptor mediated transcriptional activation. AB - Although steroid hormone receptor activation has been known to be dependent on ligand binding, we report here ligand-independent transcriptional activation of the vitamin D receptor and retinoid receptors. In these studies, CV1 cells were transiently transfected with a human vitamin D receptor (VDR) expression vector and a reporter plasmid that contains multiple copies of the rat osteocalcin vitamin D response element up-stream of the bacterial chloramphenicol acetyltransferase (CAT) gene [osteocalcin (OC)VDREtkCAT]. Treatment of cells with 10(-8) M 1,25-dihydroxyvitamin D3 resulted in a 25-fold induction of CAT activity. When cells were treated with 5-50 nM okadaic acid (OA), an inhibitor of protein phosphatase-1 and -2A, significant inductions of CAT activity (18- to 57 fold) were observed. As VDR and dopamine receptors are colocalized in certain brain regions, we also examined whether VDR-mediated transcription can be activated by dopamine. VDR was found to activate CAT gene expression in cells treated with 200-500 microM dopamine (3- to 11-fold induction) or the selective D1 agonist SKF38393 (20-fold induction). Cells were also transfected with retinoic acid receptor (RAR) or retinoid-X receptor (RXR) expression vectors and reporter plasmids that contain either a retinoic acid response element or an RXR specific response element. OA alone induced chloramphenicol acetyltransferase (CAT) activity in cells transfected with RAR alpha, RAR beta, RXR alpha, RXR beta, or RXR gamma (3- to 18-fold induction). However, OA did not affect transcription by RAR gamma, suggesting specificity of activation by OA among the retinoid receptors. Although the retinoid receptors have been detected in brain, maximum stimulation of transcription was not greater than 1.6-fold in the presence of 100-500 microM dopamine or 100 microM SKF38393 treatment. These data suggest specificity for dopamine activation among steroid hormone receptors and that phosphorylation alone, in the absence of ligand, can activate VDR- and retinoid receptor-mediated transcription. PMID- 7776975 TI - Activating transcription factor-1 is a specific antagonist of the cyclic adenosine 3'.5'-monophosphate (cAMP) response element-binding protein-1-mediated response to cAMP. AB - We have investigated the molecular basis of the variability of the somatostatin cAMP response element (CRE) function in different cell lines. All cells tested contain detectable levels of the CRE-binding protein CREB-1, which mediates transactivation in response to the cAMP-dependent protein kinase (protein kinase A), in forms that can bind to a somatostatin CRE. Although both responsive and nonresponsive cells contain CREB-1 in heterodimers with activating transcription factor-1 (ATF-1), only cells that allow a cAMP response have a significant proportion of CREB-1 in a homodimeric form. Transfection experiments demonstrate that ATF-1 is capable of antagonizing CREB-1-dependent activation, suggesting that the ability of CREB-1 to mediate a cAMP response is down-regulated by heterodimer formation with ATF-1. PMID- 7776974 TI - Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. AB - The thyroid hormone (T3) receptors (TRs) are hormone-dependent transcription factors that regulate expression of a variety of specific target genes. To help elucidate the mechanisms that underlie this transcriptional regulation and other potential TR activities, we used the yeast interaction trap to isolate clones encoding proteins that specifically interact with the ligand binding domain of the rat TR beta. Several such proteins, called Trips (TR-interacting proteins), were isolated from independent selections carried out either in the presence or absence of T3. Surprisingly, all of the Trips were dependent on hormone for interaction with the TR, with some interacting only when T3 is present and others only when it is absent. Nearly all of the Trips also show similar ligand dependent interaction with the retinoid X receptor (RXR), but none interact with the glucocorticoid receptor under any conditions. The sequences of three of the Trips predict specific functional roles: one is an apparent human homolog of a yeast transcriptional coactivator, one is a new member of a class of nonhistone chromosomal proteins, and one contains a conserved domain associated with ubiquitination of specific target proteins. Consistent with the pleiotropic effects of TR and RXR, several other Trips show significant amino acid sequence similarity with proteins involved in various regulatory pathways. The inherent transcriptional activity of the Trips was tested in yeast, and a chimeric protein consisting of a fusion of Trip4 to the bacterial LexA repressor protein is a relatively strong transcriptional activator. Similar LexA fusions to Trip9 and Trip10 had no transcriptional activity on their own but, when coexpressed with both TR and RXR, conferred T3-dependent activation to a reporter gene controlled by LexA binding sites. We suggest that this indirect T3 response provides a novel mechanism for hormonal activation of gene expression, and that studies of the Trips will provide important insights into the specific mechanisms of action of TRs and other receptors. PMID- 7776976 TI - Trout and chicken proglucagon: alternative splicing generates mRNA transcripts encoding glucagon-like peptide 2. AB - In mammals, the proglucagon gene is transcribed into a single identical mRNA in pancreas, intestine, and brain. The proglucagon mRNA encodes glucagon and two glucagon-like peptides (GLP 1 and GLP 2), whose production is regulated by tissue specific proteolytic processing. Previously characterized pancreatic proglucagon cDNAs from birds and fish encode glucagon and only one glucagon-like peptide, GLP 1. The isolation of intestinal proglucagon cDNAs from the rainbow trout, Oncorhynchus mykiss, and chicken, Gallus gallus, shows that the proglucagon gene of fish and birds also contains the sequence of a second glucagon-like peptide, GLP 2. In contrast to the proglucagon mRNAs from mammals, fish and bird proglucagon mRNAs from pancreas and intestine have different 3'-ends that are due to alternative mRNA splicing. The intestinal mRNA was found to be spliced to one or more exons, which encode GLP 2, while the pancreatic mRNA terminates within the intron between the exons encoding GLP 1 and GLP 2. These results show that proglucagon gene expression is regulated at the level of mRNA splicing and serve to reemphasize the potential biological importance of GLP 2. PMID- 7776978 TI - Regulation by estrogen through the 5'-flanking region of the mouse calbindin-D28k gene. AB - Mouse calbindin-D28k expression is regulated in vivo by estradiol in ovaries, uterus, and oviduct. To determine whether estrogen can have an effect on the transcription of the calbindin-D28k gene, the human breast cancer cells T47D were transiently transfected with a plasmid containing a 1.1 kilobase (kb) PstI/SacII fragment (-1075/+34) of the mouse calbindin gene ligated to the chloramphenicol acetyltransferase (CAT) gene and cotransfected with human estrogen receptor expression vector. T47D cells, transfected and treated with estradiol (10(-11) - 10(-7) M for 64-65 h), exhibited a dose-dependent increase in CAT activity (up to 6.2-fold). Transfection of MCF-7 breast cancer cells with the chimeric gene construct alone also resulted in an estradiol-dependent induction in CAT activity. Deletion mutant analysis demonstrated that there are two regions of the mouse calbindin-D28k promoter (between -1075/-702 and between -175/-78) that contribute to the induction by estradiol. These fragments, when linked to the thymidine kinase promoter to construct a heterologous promoter chimera, were able to convert the thymidine kinase promoter to estrogen responsiveness. In these regions there are multiple imperfect half-palindromic estrogen-responsive elements. Gel retardation assays demonstrated weak protein-DNA interactions that were competed with cold oligonucleotide containing the vitellogenin estrogen response element. These findings indicate that the mouse calbindin-D28k promoter is capable of conferring estrogen responsiveness, which may be mediated by several imperfect half-palindromic estrogen-responsive elements, and suggest, in light of previous studies concerning 1,25-dihydroxyvitamin D regulation, multiple steroid regulation of the calbindin-D28k gene. PMID- 7776977 TI - Characterization of a prolactin-inducible gene, clone 15, in T cells. AB - To examine how PRL regulates lymphocyte proliferation, a number of PRL-activated genes were identified from a PRL-dependent rat T lymphoma cell line, Nb2. One of the downstream genes in the PRL signaling cascade was identified as clone 15 (c15). PRL stimulation of quiescent Nb2 T cells results in the expression of a 1.7-kilobase c15 mRNA, which reaches maximum levels between 8 and 10 h after stimulation. Corresponding [3H]thymidine incorporation experiments show that the maximum level of c15 mRNA expression correlates with the G1/S transition phase of the cell cycle. Sequencing of approximately 1.3-kilobase cDNA revealed one open reading frame that predicts a 332-amino acid protein. In vitro transcription/translation of c15 cDNA resulted in the production of a 45 kilodalton protein. Sequence analysis revealed that the c15 open reading frame contains a potential nuclear localization signal, a very acidic region, and a carboxy-terminal region of 94 amino acids which are 68% identical and 78% similar to the nuclear movement protein, NUDC, found in Aspergillus nidulans. Such a high degree of conservation suggests that the NUDC-like motif in c15 has been conserved through evolution for an important structure and/or function. PMID- 7776979 TI - Mutually exclusive interactions of two nuclear orphan receptors determine activity of a cyclic adenosine 3',5'-monophosphate-responsive sequence in the bovine CYP17 gene. AB - ACTH-dependent transcriptional activation of the bovine CYP17 gene (the gene encoding cytochrome P450 steroid 17 alpha-hydroxylase) involves two cAMP responsive sequences (CRS1 and CRS2) located in the promoter region. Here we demonstrate that two nuclear orphan receptors, chicken ovalbumin upstream promoter transcription factor (COUP-TF) and steroidogenic factor-1 (SF-1), bind to the part of the CRS2 element that contains the repeated sequences AAGTCA and AGGTCA spaced by six nucleotides (repCRS2). Overexpression of COUP-TF and SF-1 in both steroidogenic and nonsteroidogenic cells demonstrated that SF-1 is an activator of repCRS2-dependent transcription of reporter genes. Furthermore, the SF-1-dependent transcription could be further stimulated by activation of the cAMP-dependent protein kinase. In contrast, COUP-TF alone had no effect on repCRS2-dependent reporter gene activity. Mutations that interfere with the binding of SF-1 to repCRS2 in vitro abolished the cAMP-induced activities mediated by the element in transfected Y1 cells. The mutational analysis of repCRS2 further indicated that the binding sites for the two receptors overlap, and electrophoretic mobility shift assays demonstrated that the receptors bound in a mutually exclusive manner. Overexpression of both SF-1 and COUP-TFI simultaneously demonstrated that COUP-TFI inhibited SF-1-dependent activation of reporter genes. Transient transfection experiments with a construct containing a 100/+19 base pair fragment from the bovine CYP17 gene demonstrated that SF-1 and COUP-TF had similar effects on the intact promoter as on the repCRS2/reporter gene constructs. Our data suggest that the two orphan receptors bind in a mutually exclusive manner to repCRS2 and that SF-1 is involved in the activation and COUP-TF in the repression of repCRS2-dependent transcription. PMID- 7776980 TI - Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. AB - The biosynthesis of estrogens is catalyzed by aromatase P450 (P450arom), the product of the CYP19 gene. The tissue-specific expression of the CYP19 gene is regulated by means of tissue-specific promoters through the use of alternative splicing mechanisms. Thus, transcripts containing various 5'-untranslated termini are present in human placenta and other fetal tissues, ovary, brain, and adipose stromal cells. Sequence corresponding to untranslated exon 1.4 is present in 5' termini of transcripts expressed in adipose tissue and fetal liver, as well as adipose stromal cells in primary culture in the presence of dexamethasone and fetal calf serum (FCS). Identification of hormone-responsive, tissue-specific promoter regions, as well as growth factor-response elements upstream of exon 1.4, may provide insight into the regulation of estrogen biosynthesis in adipose tissue, which is implicated in the development of breast and endometrial cancer. The goals of the present study were to define the 1.4 promoter region with respect to the start of transcription and to characterize the region(s) responsible for conferring glucocorticoid responsiveness on aromatase expression. The transcription initiation site was identified by means of primer extension and S1 nuclease protection analyses. No TATA-like sequence was evident upstream of this site. Various deletion mutations of the upstream flanking region of exon 1.4 and including part of exon 1.4 were made using polymerase chain reaction or restriction enzyme digestion. The genomic fragments were fused upstream of the chloramphenicol acetyltransferase (CAT) reporter gene. These constructs were transfected into adipose stromal cells and fetal hepatocytes in primary culture in medium containing FCS with or without dexamethasone. The -560/+10 base pair (bp) construct expressed CAT activity after a putative silencer element was deleted, and expression was induced by dexamethasone about 3-fold. Transfection of the -330/+170 bp construct, which contains an upstream glucocorticoid response element (GRE) as well as an Sp1-like sequence in untranslated exon 1.4, resulted in an 8-fold stimulation of expression of CAT activity by dexamethasone. The upstream GRE as well as the Sp1-like sequence in untranslated exon 1.4 were mutated separately, and together, to further confirm whether the GRE or Sp1 binding site play a role in the regulation of promoter 1.4-driven transcription. Mutation of either the GRE or Sp1 binding site, or both, in the -330/+170 bp construct, resulted in loss of dexamethasone-induced CAT reporter gene expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7776981 TI - Interferon-gamma inhibits macrophage insulin-like growth factor-I synthesis at the transcriptional level. AB - Spontaneous production of insulin-like growth factor-I (IGF-I) by inflammatory macrophages contributes to aberrant wound healing, but little is known about regulation of IGF-I synthesis in myeloid cells. The T cell-derived cytokine interferon-gamma (IFN gamma) inhibits several fibrogenic and angiogenic components of the wound-healing response. We have used metabolic labeling of primary colony stimulating factor-1 (CSF-1)-derived macrophages and a transformed macrophage cell line (PU5-1R) followed by immunoprecipitation to demonstrate that synthesis of the 17 kilodalton (kDa) prepro-IGF-I protein by these cells is substantially inhibited by IFN gamma. An exon 4 IGF-I/beta-actin riboprobe expression cassette was used in RNase protection assays to show that IFN gamma also reduces steady state levels of IGF-I mRNA in three different populations of macrophages in a time- and dose-dependent manner. This effect is specific for IFN gamma because neither the IFNs-alpha/beta nor lipopolysaccharide (LPS) affects expression of steady state IGF-I transcripts. Down-regulation of IGF-I mRNA by IFN gamma is dependent on de novo protein synthesis and is abrogated by coculture with cycloheximide. Nuclear run-on assays revealed that elongation of IGF-I transcripts is absent in fresh bone marrow cells but is induced several-fold after cells are cultured for 6 days with CSF-1. Treatment of these CSF-1-derived macrophages with IFN gamma for 6 h substantially inhibits synthesis of IGF-I mRNA. Studies on the decay of IGF-I mRNA in PU5-1R macrophages treated with an RNA polymerase inhibitor confirmed that the decline in IGF-I steady state mRNA in IFN gamma-treated cultures arises from an inhibition of transcription rather than from a reduction in mRNA stability. Since a variety of inflammatory mediators can induce expression of IGF-I in macrophages, inhibition of macrophage IGF-I synthesis by IFN gamma provides a mechanism by which leukocytes regulate levels of this growth factor in their microenvironment. PMID- 7776982 TI - Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene. AB - Hepatocyte-nuclear factor 3 beta (HNF-3 beta), a member of the HNF-3 gene family, is expressed in glucagon-producing islet cells and represses glucagon gene expression. We show here that at least three different HNF-3 beta transcripts that encode HNF-3 beta protein variants are present in glucagon-producing cells, HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3. Compared with the HNF-3 beta 1 cDNA, HNF-3 beta 2 cDNA lacks sequences of exon 1 while exons 1 and 4 are absent from the HNF-3 beta 3 cDNA. The deduced amino-acid (aa) sequence of HNF-3 beta 2 and HNF-3 beta 3 proteins differs from HNF-3 beta 1 by a 6-aa amino-terminal extension and by the absence of the first 30 aa, respectively. HNF-3 beta 1, HNF 3 beta 2, and HNF-3 beta 3 bind to the major enhancer of the rat glucagon gene G2 with similar affinity. By contrast to HNF-3 beta 1, which represses glucagon gene expression when overexpressed in the glucagon-producing cell line InR1G9, HNF-3 beta 2 and HNF-3 beta 3 do not affect transcriptional activity. Furthermore, cotransfection of HNF-3 beta 2 or HNF-3 beta 3 along with HNF-3 beta 1 decreases the negative effects of HNF-3 beta 1. We conclude that glucagon gene expression may be regulated by the relative abundance of the three different HNF-3 beta variants in alpha-cells. PMID- 7776983 TI - Regulated specific protein binding to a conserved region of the 3'-untranslated region of thyrotropin beta-subunit mRNA. AB - Thyroid hormone (T3) regulates the expression of rat TSH beta-subunit (TSH beta) mRNA, in part, at the posttranscriptional level, by reducing the half-life of TSH beta mRNA. The mechanism(s) mediating this alteration in mRNA stability are unknown, but previous work indicates that labile protein(s) are involved. The majority of cis-acting elements identified to date that have been implicated in the regulated destabilization of mRNAs have been located in the 3'-untranslated region (3'-UTR) of the mRNA. The 3'-UTR of rat, murine, and human TSH beta mRNA is highly conserved, and within this region is a 12-nucleotide consensus sequence, which is shared by the 3'-UTR of several other genes with unstable mRNAs. We reasoned that this homologous region could represent a binding motif for specific trans-acting RNA-binding protein(s), and that identification and characterization of such trans-acting factor(s) may provide critical insight into the mechanisms underlying T3-induced changes in TSH beta mRNA stability. Utilizing the RNA electrophoretic mobility shift assay and analysis of UV cross linked RNA-protein complexes, a cytoplasmic trans-acting factor of approximately 80-85 kilodaltons was identified from rat pituitaries and several cell lines that binds in a sequence-specific manner to the 3'-UTR of rat TSH beta mRNA. Using competitive antisense oligonucleotides, the predominant binding site was mapped to the first 41 nucleotides of the 3'-UTR, which includes the consensus region. However, sequence upstream of the consensus was also shown to be important for binding. Using RNA electrophoretic mobility shift assay, two mRNAs containing sequence homology with the consensus region, c-erbA alpha-2 and a rat ferritin pseudogene, were shown to specifically compete with rat TSH beta mRNA for binding of this factor. Remarkably, the binding activity of this factor was regulated positively by T3 within 4 h, but only with rat pituitary extracts. These data suggest that in addition to binding rat TSH beta mRNA in a sequence-specific and T3-regulated manner, this novel trans-acting RNA-binding protein may also bind to other cytoplasmic mRNAs involved in diverse intracellular processes. PMID- 7776984 TI - Age-related variation in sister chromatid exchanges and cell cycle kinetics in peripheral blood lymphocytes of healthy individuals. AB - Sister chromatid exchanges (SCEs) and cell cycle kinetics were estimated in mitogen stimulated human lymphocytes from a selected group of healthy individuals. Data were examined to evaluate the relationship between SCE frequencies and cell cycle kinetics with donor's age, sex and smoking habit. No regular relationship was observed between the mean SCE frequencies and donor's age, although significant differences were observed between the age groups. Correlation of dispersion coefficient (H) of SCE with donor's age were significant in male and female populations. For cell cycle kinetics, a highly significant age-dependent depression in replicative index (RI) was observed. Female donors possessed a slightly higher SCE frequency and RI, although the variations between the two sexes were not significant. Smoking habit resulted in a significant enhancement of SCEs. PMID- 7776985 TI - Changes of the methylation pattern of the c-myc gene during in vitro aging of IMR90 human embryonic fibroblasts. AB - DNA modification by cytosine methylation has received considerable interest in the context of mammalian cell differentiation but is discussed controversially with respect to cellular aging. As the expression of c-myc affects strongly cellular aging and terminal differentiation, we have analysed the sequence specific methylation pattern of the c-myc gene during proliferative aging in vitro of human embryonic fibroblasts. In this study, both, 5-methylcytidine sensitive restriction enzymes as well as genomic sequencing were used. The overall methylation pattern was found essentially stable during proliferative aging. However, specific hypermethylation of exon II during aging was observed. Furthermore, one specific cytidine located in the consensus sequence of the DNA binding factor PEBP2 was found completely methylated during most of the course of proliferative aging of the cells but became demethylated as the cells reached the end of their proliferative life span. Our results indicate the importance of establishing the sequence-specific changes of the methylation pattern of the genome during in vitro aging. PMID- 7776986 TI - Effect of aging and interval between primary and secondary treatment in carcinogenesis induced by neonatal exposure to 5-bromodeoxyuridine and subsequent administration of N-nitrosomethylurea in rats. AB - LIO rats were exposed to s.c. injections (3.2 mg) of a synthetic analogue of thymidine, 5-bromo-2'-deoxyuridine (BrdUrd) on the 1st, 3rd, 7th and 21st days of life and at the age of 3 or 15 months they were i.v. injected with N nitrosomethylurea (NMU) at a single dose of 10 or 50 mg/kg or with solvent. It was shown that early neonatal exposure to BrdUrd was followed by the increase in the incidence of tumor development and by the decrease of their latency. The carcinogenic effect of NMU alone correlated with the dose of the carcinogen in 3 month-old rats total and malignant tumors and tumors of some localization was decreased in the elder ones, but survival of tumor-bearing rats was decreased in the elder group as compared to the younger one. These data suggests the age related decrease in both the carcinogenic effect of NMU and in the number of events which are necessary for a tumor development. The exposure to BrdUrd was followed by the increase in the susceptibility of rats to subsequent carcinogenic effect of NMU injected at the doses of 10 or 50 mg/kg into 3- and 15-month-old rats, mostly to the tissues being target to NMU. Our data have demonstrated that the exposure to BrdUrd in the early life was followed by the irreversible initiating effect which persists over a long time in a several tissues. PMID- 7776987 TI - A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. AB - BACKGROUND: Ingestion of a large dose of the milk sugar lactose--for example, the 50-g load in 1 liter of milk--causes symptoms such as abdominal pain, diarrhea, bloating, and flatulence in the majority of people with lactose malabsorption. It is uncertain whether the ingestion of more common doses of lactose, such as the amount in 240 ml (8 oz) of milk, causes symptoms. Some people insist that even smaller quantities of milk, such as the amount used with cereal or coffee, cause severe gastrointestinal distress. METHODS: In a randomized, double-blind, crossover trial, we evaluated gastrointestinal symptoms in 30 people (mean age, 29.4 years; range, 18 to 50) who reported severe lactose intolerance and said they consistently had symptoms after ingesting less than 240 ml of milk. The ability to digest lactose was assessed by measuring the subjects' end-alveolar hydrogen concentration after they ingested 15 g of lactose in 250 ml of water. Subjects then received either 240 ml of lactose-hydrolyzed milk containing 2 percent fat or 240 ml of milk containing 2 percent fat and sweetened with aspartame to approximate the taste of lactose-hydrolyzed milk; each type of milk was administered daily with breakfast for a one-week period. Using a standardized scale, subjects rated the occurrence and severity of bloating, abdominal pain, diarrhea, and flatus and recorded each passage of flatus. RESULTS: Twenty-one participants were classified as having lactose malabsorption and nine as being able to absorb lactose. During the study periods, gastrointestinal symptoms were minimal (mean symptom-severity scores for bloating, abdominal pain, diarrhea, and flatus between 0.1 and 1.2 [1 indicated trivial symptoms; and 2, mild symptoms]). When the periods were compared, there were no statistically significant differences in the severity of these four gastrointestinal symptoms. For the lactose-malabsorption group, the mean (+/- SEM) difference in episodes of flatus per day was 2.5 +/- 1.1 (95 percent confidence interval, 0.2 to 4.8). Daily dietary records indicated a high degree of compliance, with no additional sources of lactose reported. CONCLUSIONS: People who identify themselves as severely lactose-intolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance. When lactose intake is limited to the equivalent of 240 ml of milk or less a day, symptoms are likely to be negligible and the use of lactose-digestive aids unnecessary. PMID- 7776988 TI - Optimal oral anticoagulant therapy in patients with mechanical heart valves. AB - BACKGROUND: The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of anticoagulation. METHODS: Data were collected on all patients with mechanical heart valves who have been seen at four regional Dutch anticoagulation clinics since 1985. The primary outcome events were episodes of thromboembolism or major bleeding. The intensity-specific incidence of each type of event was calculated as the number of events that occurred at a certain intensity of anticoagulation (expressed in terms of the international normalized ratio [INR]) divided by the number of patient-years during which the INR was at this level in the total patient population. RESULTS: A total of 1608 patients were followed during 6475 patient-years. Cerebral embolism occurred in 43 patients (0.68 per 100 patient-years) and peripheral embolism in 2 (0.03 per 100 patient-years). Intracranial and spinal bleeding occurred in 36 patients (0.57 per 100 patient-years) and major extracranial bleeding in 128 (2.1 per 100 patient-years). The optimal intensity of anticoagulation, at which the incidence of both complications was lowest, was achieved when the INR was between 2.5 and 4.9. CONCLUSIONS: The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended. PMID- 7776989 TI - Apoptosis and loss of renal tissue in polycystic kidney diseases. AB - BACKGROUND: Polycystic kidney disease is characterized by the enlargement of renal cysts, interstitial fibrosis, and gradual loss of normal renal tissue in association with progressive deterioration of renal function. The process causing the progressive loss of renal tissue is unknown, but it could be the result of a form of programmed cell death known as apoptosis. METHODS: We assayed apoptotic DNA fragmentation in normal and polycystic kidneys biochemically by gel electrophoresis and histochemically by in situ end-labeling. A DNA-specific dye, Hoechst 33258, was used to detect morphologic apoptosis in renal samples from patients with normal kidneys, polycystic kidney disease, and other kidney diseases. RESULTS: Apoptotic DNA fragmentation was detected in polycystic kidneys from 5 patients without renal failure and 11 patients with renal failure but not in kidneys from 12 patients with no renal disease. In situ end-labeling revealed apoptotic cells in glomeruli, in cyst walls, and in both cystic and noncystic tubules of the polycystic kidneys. No tubular apoptosis was detected in renal biopsy specimens from five patients with IgA nephropathy, three patients with nephrosclerosis, two patients with focal glomerulosclerosis, one patient with diabetic nephropathy, six patients with acute tubular necrosis, or four patients with acute and four patients with chronic renal-transplant rejection. The capacity of polycystic kidney cells to undergo apoptosis was retained in vitro in the absence of uremia, ischemia, and other confounding pathologic conditions. CONCLUSIONS: Apoptotic loss of renal tissue may be associated with the progressive deterioration of renal function that occurs in patients with polycystic kidney disease. PMID- 7776990 TI - The treatment of scabies with ivermectin. AB - BACKGROUND: Ivermectin is an anthelmintic agent that has been a safe, effective treatment for onchocerciasis (river blindness) when given in a single oral dose of 150 to 200 micrograms per kilogram of body weight. Anecdotal reports of improvement in patients who suffered from infestation with the mite Sarcoptes scabiei suggest that the ectoparasitic disease scabies might be treated with ivermectin. METHODS: We conducted an open-label study in which ivermectin was administered in a single oral dose of 200 micrograms per kilogram to 11 otherwise healthy patients with scabies and to 11 patients with scabies who were also infected with the human immunodeficiency virus (HIV), 7 of whom had the acquired immunodeficiency syndrome. All patients received a full physical and dermatologic examination; scrapings from the skin of all patients tested positive for scabies. Patients were reexamined two and four weeks after treatment, when the scrapings for scabies were repeated. The patients used no other scabicides during the 30 days before ivermectin treatment or during the 4-week study period. RESULTS: None of the 11 otherwise healthy patients had evidence of scabies four weeks after a single dose of ivermectin. Of the 11 HIV-infected patients, 2 had < or = 10 scabies lesions before treatment, 3 had 11 to 49 lesions, 4 had > or = 50 lesions, and 2 had heavily crusted skin lesions. In eight of the patients the scabies was cured after a single dose of ivermectin. Two patients received a second dose two weeks after the first. Ten of the 11 patients with HIV infection (91 percent) had no evidence of scabies four weeks after their first treatment with ivermectin. CONCLUSIONS: The anthelmintic agent ivermectin, given in a single oral dose, is an effective treatment for scabies in otherwise healthy patients and in many patients with HIV infection. PMID- 7776991 TI - Images in clinical medicine. Polycystic liver and kidney disease. PMID- 7776992 TI - Gastric carcinoma. PMID- 7776993 TI - Jumping genes and the immunoglobulin V gene system. PMID- 7776994 TI - Clinical problem-solving. Diverted by the chief complaint. PMID- 7776995 TI - Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. AB - BACKGROUND: A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation. However, both the targeted and the actual levels of anticoagulation differed widely among the studies, and a number of studies failed to report standardized prothrombin-time ratios as international normalized ratios (INRs). We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications. METHODS: We calculated INR-specific incidence rates for both ischemic and major hemorrhagic events occurring in 214 patients who received anticoagulant therapy in the European Atrial Fibrillation Trial, a secondary-prevention trial in patients with nonrheumatic atrial fibrillation and a recent episode of minor cerebral ischemia. RESULTS: The optimal intensity of anticoagulation was found to lie between an INR of 2.0 and an INR of 3.9. No treatment effect was apparent with anticoagulation below an INR of 2.0. The rate of thromboembolic events was lowest at INRs from 2.0 to 3.9, and most major bleeding complications occurred with treatment at intensities with INRs of 5.0 or above. CONCLUSIONS: To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation and a recent episode of cerebral ischemia, the target value for the INR should be set at 3.0, and values below 2.0 and above 5.0 should be avoided. PMID- 7776997 TI - Lactose intolerance. PMID- 7776996 TI - Managed care and the morality of the marketplace. PMID- 7776998 TI - Aiming for safe anticoagulation. PMID- 7776999 TI - Polycystic kidney disease--there goes the neighborhood. PMID- 7777000 TI - Performance reports on quality--prototypes, problems, and prospects. PMID- 7777002 TI - Intramuscular injections and vaccine-associated poliomyelitis. PMID- 7777001 TI - Intramuscular injections and vaccine-associated poliomyelitis. PMID- 7777003 TI - Intramuscular injections and vaccine-associated poliomyelitis. PMID- 7777004 TI - Genetic predisposition to Hodgkin's disease. PMID- 7777005 TI - Hodgkin's disease and HIV infection. PMID- 7777006 TI - Pel-Ebstein fever. PMID- 7777007 TI - Transplantation of cord-blood cells. PMID- 7777009 TI - Transplantation of cord-blood cells. PMID- 7777008 TI - Transplantation of cord-blood cells. PMID- 7777011 TI - Abuse and neglect of elderly persons. PMID- 7777010 TI - Treatment of life-threatening infantile hemangiomas with vincristine. PMID- 7777012 TI - Abuse and neglect of elderly persons. PMID- 7777015 TI - Occupational asthma. PMID- 7777013 TI - Images in clinical medicine. Transverse leukonychia. PMID- 7777016 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 21-1995. A 33-year-old man with a sore throat followed by swelling and pain in the leg. PMID- 7777014 TI - A pregnancy-prevention program in women of childbearing age receiving isotretinoin. AB - BACKGROUND: Isotretinoin is effective in treating severe acne, but it is also teratogenic. To minimize pregnancies among exposed women, the manufacturer, together with the U.S. Food and Drug Administration, implemented a multicomponent Pregnancy Prevention Program in 1988. We report the results of an ongoing survey designed to assess compliance with this program. METHODS: Treated women enrolled in the survey through their physician, by filling out a form in the medication package, or by calling a toll-free telephone number. They were randomly assigned to be followed by telephone or by mail. Telephone interviews were conducted at the start of therapy, in the middle of it, and 6 months after it ended; mailed questionnaires were completed 6 months after therapy ended (median duration of therapy, 20 weeks). RESULTS: Between 1989 and 1993, 177,216 eligible women enrolled in the survey. Interviews with 24,503 women within one month of enrollment revealed that 99 percent had been told to avoid pregnancy. At that time, approximately 54 percent were not sexually active (of whom 37 percent used contraception) and 42 percent were sexually active (of whom 99 percent used contraception); 4 percent were infertile. Among 124,216 women with completed telephone or mail follow-up results, there were 402 pregnancies during therapy (3.4 per 1000 courses of isotretinoin); 72 percent of the pregnant women had elective abortions, 16 percent spontaneous abortions, 3 percent ectopic pregnancies, and 8 percent live births. CONCLUSIONS: The pregnancy rate among women receiving isotretinoin therapy was substantially lower than that in the general population and was compatible with the characteristics and behavior of the enrolled women. PMID- 7777017 TI - Amiodarone in patients with heart failure. PMID- 7777018 TI - What causes wasting in AIDS? PMID- 7777019 TI - Protecting the embryo from X-rated drugs. PMID- 7777020 TI - Povidone-iodine to prevent ophthalmia neonatorum. PMID- 7777021 TI - Povidone-iodine to prevent ophthalmia neonatorum. PMID- 7777023 TI - Clinical problem-solving: decision making by analogy. PMID- 7777022 TI - Clinical problem-solving: decision making by analogy. PMID- 7777024 TI - Clinical problem-solving: decision making by analogy. PMID- 7777025 TI - Clinical problem-solving: decision making by analogy. PMID- 7777026 TI - Clinical problem-solving: decision making by analogy. PMID- 7777027 TI - Clinical problem-solving: decision making by analogy. PMID- 7777028 TI - Gastrointestinal cancer and the cystic fibrosis gene. PMID- 7777029 TI - Images in clinical medicine: corticosteroid osteonecrosis. PMID- 7777030 TI - Images in clinical medicine: corticosteroid osteonecrosis. PMID- 7777031 TI - Medical aspects of the persistent vegetative state--a correction. The Multi Society Task Force on PVS. PMID- 7777032 TI - Trans fatty acids in margarine. PMID- 7777033 TI - Energy expenditure and wasting in human immunodeficiency virus infection. AB - BACKGROUND: Increased expenditure of energy at rest has been considered a contributing factor to the negative energy balance and weight loss that occur in patients with human immunodeficiency virus (HIV) infection. However, the true determinant of energy balance is not resting but total energy expenditure. We sought to determine the contribution of total energy expenditure to weight changes in patients with HIV-associated wasting. METHODS: We performed 51 assessments of energy metabolism in 27 men with HIV infection at different stages of disease, including periods of both rapid and slow weight loss. Resting energy expenditure was measured by indirect calorimetry, total energy expenditure by the doubly-labeled-water technique, and energy intake by recording the weight of food consumed. The results were compared with the rate of weight loss or gain. RESULTS: The mean (+/- SD) total energy expended by the HIV-infected men was 2750 +/- 670 kcal per day, no more than that expended by normal men. There was a significant positive relation between total energy expenditure and the rate of weight change (r = 0.61, P < 0.001); thus, during rapid weight loss, total energy expenditure was reduced to 2180 +/- 580 kcal per day (P = 0.009), primarily because of reduced physical activity. During rapid weight loss, the negative energy balance (-850 +/- 580 kcal per day) was primarily the result of the reduction in energy intake, to 1330 +/- 610 kcal per day; intake correlated strongly with the rate of weight change (r = 0.84, P < 0.001). CONCLUSIONS: In patients with HIV infection, total energy expenditure is reduced during episodes of weight loss. Reduced energy intake, not elevated energy expenditure, is the prime determinant of weight loss in HIV-associated wasting. PMID- 7777034 TI - Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. AB - BACKGROUND: There is little information on the incidence and natural history of neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: We studied patients with newly diagnosed NIDDM and control subjects both at base line and 5 and 10 years later. Polyneuropathy was diagnosed on the basis of clinical criteria (pain and paresthesias) and electrodiagnostic studies (nerve conduction velocity and response-amplitude values). We investigated the relation between metabolic variables (results of oral glucose-tolerance tests, serum lipid and insulin concentrations, and glycosylated hemoglobin values) and the development of polyneuropathy. RESULTS: In 10 years, 36 patients with NIDDM and 8 control subjects died; 86 patients and 121 control subjects completed the study. When the study ended, 18 percent of the patients were being treated only with diet, 59 percent with oral hypoglycemic drugs alone, 12 percent with insulin alone, and 11 percent with both insulin and oral hypoglycemic agents. At base line the prevalence of definite or probable polyneuropathy among the patients with NIDDM was 8.3 percent, as compared with 2.1 percent among the control subjects. These values 10 years later were 41.9 percent and 5.8 percent, respectively. The number of patients with NIDDM who had nerve-conduction abnormalities in the legs and feet increased from 8.3 percent at base line to 16.7 percent after 5 years and to 41.9 percent after 10 years. The decrease in sensory and motor amplitudes, indicating axonal destruction, was more pronounced than the slowing of the nerve conduction velocities, which indicates demyelination. Among the patients with NIDDM, those with polyneuropathy had poorer glycemic control than those without. Low serum insulin concentrations before and after the oral administration of glucose were associated with the development of polyneuropathy, regardless of the degree of glycemia. CONCLUSIONS: The prevalence of polyneuropathy among patients with NIDDM increases with time, and the increase may be greater in patients with hypoinsulinemia. PMID- 7777035 TI - Developmental effects of fumonisin B1-containing Fusarium moniliforme culture extract in CD1 mice. AB - Pregnant Charles River CD1 mice were treated with a semipurified extract of Fusarium moniliforme culture containing 0, 12.5, 25, 50 or 100 mg FB1/kg each day orally (diluted in distilled water) between gestational days (GD) 7 and 15 to evaluate the developmental toxicity of FB1. Following sacrifice of dams on GD 18, litters were examined for gross abnormalities and divided equally for skeletal or visceral examination by routine techniques. Significant maternal mortality was observed at doses of 50 and 100 mg FB1/kg. Dose-dependent decreases in maternal body weight gains, number of live offsprings per litter, and mean body weight of the offspring were produced at FB1 doses of 25 mg/kg or higher. The percentage of implants resorbed increased at all doses in a dose-dependant manner. A dose dependant increase, except at the lowest dose tested, in the incidence of ossification deficits involving digits and sternum, short and wavy ribs, and hydrocephalus of lateral and third ventricles was also evident. Cleft palate was seen only at the highest FB1 dose. Maternal intoxication manifested as a dose dependant increase in the severity of ascites associated mainly with increased histopathologic scores reflecting hepatocellular damage at day 18. Concommittant increases in serum alanine amino transferase (ALT) on GD 12, reflecting parenchymal liver cell damage, was also observed at all doses above 12.5 mg of FB1/kg. These results suggest that FB1-containing F. moniliforme culture extract is developmentally toxic in mice, and that this toxicity may be mediated by maternal hepatotoxicity. PMID- 7777036 TI - Experimental paracoccidioidomycosis of hamster inoculated in the cheek pouch. AB - We compared the granuloma morphology and immune response of hamsters inoculated with Paracoccidioides brasiliensis (Pb) into the cheek pouch, which lacks lymphatic drainage, and into the footpad, which is rich in lymphatics. Our objective was to better understand the modulation of Pb granuloma in an immunocompetent animal inoculated in an immunologically privileged site. The humoral immune response (ELISA) and cell mediated immunity (footpad test) became positive on days 7 and 14, respectively in animals inoculated into footpad and on days 35 and 60 in animals inoculated into the pouch. Typical epithelioid granulomas were observed at both sites on day 14. The number of fungi gradually decreased from the beginning of the experiment in footpad lesions, but only after day 35 in pouch granulomas, when cell mediated immunity was detectable. The results indicate that typical epithelioid paracoccidioidomycotic granulomas may develop in the absence of a detectable immune response; however, they are incapable of controlling fungal reproduction. Lack of lymphatic drainage delays the appearance of a detectable immune response, but with time fungi escape from the pouch, elicit an immune response and reach other organs. Our results further indicate the importance of the lymphatics in the pathogenesis of paracoccidioidomycosis. PMID- 7777037 TI - A case of chronic necrotizing pulmonary aspergillosis due to Aspergillus nidulans. AB - A 55-year old man without immunosuppression clinically showed a coin lesion in the right lower lung on the chest radiographs. Aspergillus nidulans was isolated and identified in both trans-bronchial lung biopsy specimen and resected tissue. The specimens revealed characteristics of chronic necrotizing pulmonary aspergillosis pathologically. Very few reports on cases of pulmonary aspergillosis due to A. nidulans exist, and we were not able to find any reports of similar cases. This case may be the first reported case of chronic necrotizing pulmonary aspergillosis due to A. nidulans. PMID- 7777038 TI - Effect of amphotericin B on the lipids of five different strains of Cryptococcus neoformans. AB - Cells of five strains of Cryptococcus neoformans were obtained for partial analysis of lipid composition. Quantitative analysis of lipids and sterols were completed, as well as qualitative analysis of sterols by thin-layer chromatography and by the ultraviolet spectra. Such determinations were made on cells cultured in the absence and presence of amphotericin B at sub-MIC (minimal inhibitory concentration) levels. Marked alterations of the lipid and sterol contents were observed in the amphotericin B-treated cells. Moreover, ergosterol disappeared in these antibiotic-exposed cells. It is concluded that amphotericin B altered the lipid profiles, especially sterols of C. neoformans. PMID- 7777040 TI - NIH panel to monitor peer review in action. PMID- 7777039 TI - SDS-PAGE separation of dermatophyte antigens, and western immunoblotting in feline dermatophytosis. AB - Water-soluble antigens liberated from the disrupted mycelium of nine dermatophytes (seven isolates of Microsporum canis, one each of Microsporum gypseum and Trichophyton mentagrophytes) were compared by analytical slab SDS PAGE. No substantial differences were observed between the protein bands of the M. Canis isolates, but certain distinctive bands were apparent in the other two species examined. Western immunoblotting using M. canis-derived antigens separated by SDS-PAGE was used to investigate the humoral immune response in 79 cats with naturally-occurring dermatophytosis (72 with M. canis, six with M. gypseum and one with T. mentagrophytes) and this information was compared to results of immunoblots from 46 control (non-dermatophyte exposed) cats. Seven dominant bands (bands which occurred frequently and stained heavily) were identified in immunoblots from the dermatophyte-infected cats with apparent molecular weights varying between 39 and 120 kD. None of these bands were totally specific markers for dermatophytosis as a variable proportion of the control cats showed reactivity to all these proteins. However, most (73%) of the dermatophyte infected cats showed reactivity to six or seven of the identified bands whereas most (80%) of the control cats showed reactivity to between zero and three of these bands (p < 0.005). Western immunoblotting could be used to select individual immunodominant antigens for further evaluation of protective (cell mediated) immunity. PMID- 7777041 TI - US cardiologist found guilty of theft. PMID- 7777042 TI - 'Science and reason' forum finds enemies all around. PMID- 7777043 TI - 'Euro-lab' scientists seek fairer deal on pay. PMID- 7777044 TI - Panel offers compromise on food labelling. PMID- 7777045 TI - French journalism defended. PMID- 7777046 TI - Necessary brain. PMID- 7777047 TI - Parents' rights. PMID- 7777049 TI - Biotechnology. Making selection work. PMID- 7777048 TI - Cognitive function. Acetylcholine revisited. PMID- 7777051 TI - Is thalidomide mutagenic? PMID- 7777050 TI - Neurotransmission. Keeping synapses up to speed. PMID- 7777052 TI - Sex of the last wild Spix's macaw. PMID- 7777053 TI - Delivery of a nematocyst toxin. PMID- 7777054 TI - Bacteriorhodopsin as a model for proton pumps. AB - According to a long-standing hypothesis, membrane pumps function by flip-flopping between two protein conformations that allow alternative access of the ion binding site to the two membrane surfaces. Site-specific mutagenesis, time resolved spectroscopy and X-ray diffraction confirm this mechanism for bacteriorhodopsin, and implicate change of electrostatic interaction at the active site as the trigger for the global protein conformation change during the proton transport cycle. PMID- 7777055 TI - Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. AB - Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex. PMID- 7777056 TI - Essential role of neocortical acetylcholine in spatial memory. AB - The cholinergic system plays a crucial role in learning and memory. Lesions of cholinergic nuclei, pharmacological manipulations of cholinergic systems, intracerebral transplantation of fetal tissue and anatomical changes in cholinergic pathways during ageing have all been correlated with altered cognitive behaviour. However, it has not been proved that regional acetylcholine is causally required for learning and memory. Here we describe how we achieved a permanent and selective impairment of learning and memory by damaging the nucleus basalis magnocellularis, a nucleus that provides the major cholinergic innervation of the neocortex, in adult rats. To test the hypothesis that acetylcholine is essential for restoration of cognitive function, we implanted genetically modified cells that produce acetylcholine into denervated neocortical target regions. After grafting, rats with increased neocortical acetylcholine levels showed a significant improvement in a spatial navigation task. Acetylcholine is thus not only necessary for learning and memory, as previously argued, but its presence within the neocortex is also sufficient to ameliorate learning deficits and restore memory following damage to the nucleus basalis. PMID- 7777057 TI - Essential functions of synapsins I and II in synaptic vesicle regulation. AB - Synaptic vesicles are coated by synapsins, phosphoproteins that account for 9% of the vesicle protein. To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both. Mice lacking synapsins are viable and fertile with no gross anatomical abnormalities, but experience seizures with a frequency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post-tetanic potentiation and severe synaptic depression upon repetitive stimulation. Intrinsic synaptic-vesicle membrane proteins, but not peripheral membrane proteins or other synaptic proteins, are slightly decreased in individual knockouts and more severely reduced in double knockouts, as is the number of synaptic vesicles. Thus synapsins are not required for neurite outgrowth, synaptogenesis or the basic mechanics of synaptic vesicle traffic, but are essential for accelerating this traffic during repetitive stimulation. The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles. PMID- 7777058 TI - Distinct pools of synaptic vesicles in neurotransmitter release. AB - Nerve terminals are unique among cellular secretory systems in that they can sustain vesicular release at a high rate. Although little is known about the mechanisms that account for the distinctive features of neurotransmitter release, it can be assumed that neuron-specific proteins are involved. One such protein family, the synapsins, are believed to regulate neurotransmitter release through phosphorylation-dependent interactions with synaptic vesicles and cytoskeletal elements. Here we show that clusters of vesicles at synaptic release sites are composed of two pools, a distal pool containing synapsin and a proximal pool devoid of synapsin and located adjacent to the presynaptic membrane. Presynaptic injection of synapsin antibodies resulted in the loss of the distal pool, without any apparent effect on the proximal pool. Depletion of this distal pool was associated with a marked depression of neurotransmitter release evoked by high frequency (18-20 Hz) but not by low-frequency (0.2 Hz) stimulation. Thus the availability of the synapsin-associated pool of vesicles seems to be required to sustain release of neurotransmitter in response to high-frequency bursts of impulses. PMID- 7777059 TI - Glucosylation of Rho proteins by Clostridium difficile toxin B. AB - Toxin A and B, the major virulence factors of Clostridium difficile, are the causative agents of antibiotic-associated pseudomembranous colitis. In cultured cell lines their potent cytotoxicity results from their ability to induce disaggregation of the microfilament cytoskeleton. Toxin B acts on the low molecular-mass GTPase RhoA, which is involved in the regulation of the actin cytoskeleton. We report here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid threonine at position 37. The modification was identified and localized by tandem electrospray mass spectrometry. UDP-glucose selectively serves as cosubstrate for the monoglucosylation reaction catalysed by toxin B. Microinjection of RhoA previously glucosylated by toxin B into monolayer cells caused disaggregation of actin filaments, indicating a dominant-negative activity of glucosylated RhoA. PMID- 7777060 TI - Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. AB - D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on human chromosome 9p21 (refs 12-14). The frequent deletion or mutation of CDKN2 in tumour cells suggests that p16 acts as a tumour suppressor. We show that wild-type p16 arrests normal diploid cells in late G1, whereas a tumour-associated mutant of p16 does not. Significantly, the ability of p16 to induce cell-cycle arrest is lost in cells lacking functional RB, including primary fibroblasts from Rb-/- mouse embryos. Thus, loss of p16, overexpression of D-cyclins and loss of RB have similar effects on G1 progression, and may represent a common pathway to tumorigenesis. PMID- 7777061 TI - Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. AB - The cyclin-dependent kinase inhibitor p16 is a candidate tumour-suppressor protein that maps to a genomic locus strongly associated with familial melanoma and other tumour types. Screening of primary tumours and linkage analysis of familial melanoma pedigrees have identified many potential mutations in p16, but the functional significance of these sequence variants has remained unclear. We report here that p16 can act as a potent and specific inhibitor of progression through the G1 phase of the cell cycle, and we demonstrate that several tumour derived alleles of p16 encode functionally compromised proteins. The ability of p16 to arrest cell-cycle progression generally correlates with inhibition of cyclin D1/Cdk4 kinase activity in vitro, with two exceptions among the alleles tested. In vivo, the presence of functional retinoblastoma protein appears to be necessary but may not be sufficient to confer full sensitivity to p16-mediated growth arrest. Our results provide support for the notion that p16 is an important cell-cycle regulator whose inactivation contributes to the outgrowth of human tumours. PMID- 7777062 TI - A two-step mechanism for 5' and 3' splice-site pairing. AB - A fundamental question in the splicing of precursor messenger RNA is how the 5' and 3' splice sites are recognized and paired during the splicing reaction. It has been proposed that spliceosome assembly in metazoan pre-mRNAs can be initiated through interaction between the 3' splice site and specific sequence elements on the downstream exon (an exonic enhancer or a 5' splice site). Pairing of the intronic 5' and 3' splice sites occurs subsequently. We report here that 5' and 3' splice sites located on separate synthetic pre-mRNA substrates can be efficiently trans-spliced if the 3' trans-splicing substrate contains these downstream sequence elements. Moreover, selection of the trans 5' splice site can occur after the second pre-spliceosomal complex A has assembled on the 3' trans splicing substrate. Thus our data demonstrate that 5' and 3' splice-site pairing in metazoans can occur in two distinct steps. PMID- 7777063 TI - Direct NMR evidence for an intermediate preceding the rate-limiting step in the unfolding of ribonuclease A. AB - It is commonly believed that there are no detectable intermediates in the kinetic unfolding reactions of small proteins. If such intermediates could be found, they would give important information about the nature of the transition state for unfolding, which is thought to occur close to the native state. We report here that one-dimensional proton magnetic resonance spectra recorded during the unfolding of ribonuclease A provide direct evidence for at least one unfolding intermediate in which side chains are free to rotate. This intermediate appears to be a 'dry molten globule' of the kind hypothesized by Shakhnovich and Finkelstein. PMID- 7777064 TI - 36th Spring meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology. Mainz, March 14-17, 1995. Abstracts. PMID- 7777065 TI - Cardiovascular risks for hemodialysis and peritoneal dialysis patients. PMID- 7777067 TI - Donor rule, DOT budget gives AOPO issues to consider at upcoming meeting. PMID- 7777068 TI - The future of nephrology nursing care: a preview of 1995-1996 ANNA activities. PMID- 7777066 TI - Transplanting the older patient: what are the risks--and successes? PMID- 7777070 TI - Smile. Smile. Smile. PMID- 7777069 TI - The new year's challenges for nursing. PMID- 7777071 TI - Seeking success: effective orientation programs for experienced faculty. AB - Experienced faculty who change academic positions must adjust quickly to a new academic and clinical setting. Although strategies to facilitate integration for faculty new to the role are available, integrating experienced faculty presents a different challenge, and these strategies are not available in the literature. This article presents relevant orientation strategies for both clinical and academic settings. PMID- 7777072 TI - Budget, costs, and health care reform. PMID- 7777073 TI - Interdisciplinary faculty and student practice in a nurse-managed campus wellness program. AB - The concept of nurse-managed care in centers for nursing is a growing phenomenon in this era of health care reform. Nursing faculty are utilizing nurse-managed centers as alternative sites for clinical experiences and faculty practice. In this paper the authors highlight interdisciplinary faculty and student practice for a Campus Wellness Program at a midwestern university. Empowering faculty and students, and offering needed health promotion services to the university community, are addressed. Historical background, administrative, practice and educational challenges, and triumphs will be presented. PMID- 7777074 TI - Ethical implications of the Human Genome Diversity Project. PMID- 7777075 TI - A collaborative effort for rural health. AB - Collaboration between the W.K. Kellogg Foundation and a school of nursing helped to meet health care and environmental needs of the residents in two rural counties burdened with poverty and illiteracy. This endeavor also affords the faculty and students in the school of nursing opportunities to work with underserved populations in rural areas. The project continues its community service through evolving programs. PMID- 7777076 TI - Action research: a method for practitioners. AB - Nursing research has frequently been criticized for its inability to shape or be shaped by clinical practice. One method that involves clinicians and researchers in the pursuit of research and change is action research. The purpose of this paper is to present action research as a technique that combines grounded methods with organizational change to enhance clinical practice, an approach widely used in Australia and England. The presentation includes the steps in action research. Examples of nursing research conducted are also examined. The discussion focuses on techniques that enhance, maintain, or increase the scientific rigor of the methods. PMID- 7777077 TI - Fetal well-being. III: Strategies to diminish liability and improve patient care in all trimesters. PMID- 7777078 TI - Hidden scars: posttraumatic stress disorder. AB - Memories of traumatic incidents or experiences can cause deep but invisible scars. Without intervention, the emotional pain associated with the incident can continue unabated. For the most part, painful memories are likely to be suppressed. However, when a memory is "triggered" for some reason, a variety of symptoms may occur which may be termed "posttraumatic stress disorder" (PTSD). A nurse can use an understanding of unhealed psychological scars to gain awareness of unresolved personal stress. In addition to personal reflection, as nurses assess and care for patients, it is important to be alert to indications of unresolved emotional pain. PMID- 7777079 TI - [Rehabilitation of the CVA patient in the nursing home]. PMID- 7777080 TI - [The preoperative examination; reconsideration]. PMID- 7777081 TI - [Who should carry out which preoperative examination when?]. PMID- 7777082 TI - [Preoperative internist consultation. I. General aspects and management in diabetes mellitus and obstructive lung disease]. PMID- 7777083 TI - [Preoperative internist consultation. II. Management in hypertension and cardiac disease]. PMID- 7777084 TI - [Outpatient preoperative examination by the anesthesiologist. I. Fewer procedures and preoperative hospital days]. AB - OBJECTIVE: To study the effect of the reorganisation of the preoperative screening on the volume of laboratory and function tests, and on preoperative hospital days. SETTING: General Hospital De Weezenlanden, Zwolle, The Netherlands. DESIGN: Retrospective study. METHOD: In The Netherlands the surgeon is responsible for the preoperative screening (anamnesis and general examination). In 1992 the preoperative screening was reorganised and it was carried out in the outpatient department under the responsibility of the anaesthesiologist. Laboratory and function tests were only performed if indicated. Data on 3122 patients, operated in 1991, were compared with the data on 3258 patients from 1992. Multiple regression analysis and chi-square test were used. RESULTS: The proportions of the patients subjected to laboratory tests, ECG or a chest X-ray decreased from 90%, 55%, and 50% respectively in 1991 to 53%, 43% and 10% in 1992 (p < 0.05). Admission on the day of surgery increased from 13% in 1991 to 21% in 1992 (p < 0.01). Clinical preoperative evaluation with admission more than 1 day before surgery, decreased from 5% in 1991 to 4% in 1992 (p = 0.02). The mean duration of the hospital stay before the operation decreased from 0.79 day per patient in 1991 to 0.65 in 1992 (p = 0.02). CONCLUSION: If the preoperative screening is carried out by the anaesthesiologist, all the patients have the opportunity to meet the anaesthesiologist before the operation. The number of preoperative hospital days can be reduced by outpatient preoperative screening. Laboratory and function testing on only if indicated reduces the volume of the laboratory tests, ECGs and chest X-rays. PMID- 7777085 TI - [Outpatient preoperative examination by the anesthesiologist. II. Patient satisfaction]. AB - OBJECTIVE: To determine patient satisfaction after the reorganisation of the preoperative screening. SETTING: General Hospital De Weezenlanden, Zwolle, The Netherlands. DESIGN: Retrospective patient interview. METHOD: Before the reorganisation, the preoperative screening was performed clinically under the responsibility of the consultant surgeon. Thereafter it was performed in the outpatient department by the anaesthesiologist. Patients who had had two similar operations within two and a half years, one before and one after the reorganisation, were interviewed at home regarding the different methods of preoperative screening (n = 94). RESULTS: The preoperative screening had a reassuring effect on patients. 72% considered preoperative anaesthesia information important. The number of hospital visits before the operation did not significantly increase after the screening was reorganised. There was little objection to attending the hospital for preoperative screening (12%). Most patients (60%) had no preference for the previous or the present method of screening. Patients who remembered the interview with the anaesthesiologist (56%) preferred the new method (score: 8.2 on a scale 0-10; score of the former method: 7.6; p < 0.01). A larger number of these had the opportunity to ask questions (p = 0.01) and more patients had received attention from the anaesthesiologist (p < 0.01). 75% of the patients had received sufficient preoperative anaesthesia information. 28% of the patients wanted to see the anaesthesiologist again after admission. CONCLUSIONS: Preoperative screening reassures and informs the patient. The patients who could remember the interview with the anaesthesiologist preferred the preoperative screening in the outpatient department. A considerable number of the patients wanted to see the anaesthesiologist again after admission. PMID- 7777086 TI - [Geriatric rehabilitation in a nursing home and the Barthel Index as a parameter]. AB - OBJECTIVE: To analyse patient characteristics and the results of rehabilitation among patients admitted for rehabilitation to a nursing-home. DESIGN: Retrospective study. SETTING: St. Jozefsheil in Bakel, part of the Stichting Verpleeghuizen Gewest Helmond Nursing Homes Foundation, District Helmond, SVGH). METHOD: On all 60 patients admitted to the SVGH homes in 1987, information was obtained from medical, paramedical and nursing records. The Barthel index was determined on admission and at discharge and the differences were tested statistically using a t-test. RESULTS: 37 female and 23 male patients were admitted, with a median age of 75.5 years. 62% had had a cerebrovascular accident and 90% were referred from the hospital, mainly by the neurologist. The median hospitalization time was 9 weeks and the waiting list for a nursing home 2.9 weeks. In 1990, 47% of the patients were discharged, after a median rehabilitation time of 15 weeks; 23% had died and 30% remained in the nursing home. Among the discharged patients the increase in mean Barthel index from admission to discharge was 17.9 points. The difference in mean Barthel index at admission compared with non-discharged patients was 35.4 points and that compared with the decreased patients 37.7 points. For the 23 patients discharged within one year compared with the 5 patients discharged after more then one year the difference was 13.6 points. The mean Barthel index at admission of the 14 discharged patients living alone was 21 points more then that of the 10 discharged patients living with a partner. At discharge this difference was 9.9 points. CONCLUSION: The Barthel index appears useful for evaluation and comparison of results of (geriatric) rehabilitation. PMID- 7777087 TI - [Balloon occlusion of the internal carotid artery in the treatment of inoperable aneurysms]. AB - Three patients, women of 46, 63 and 47 years old, with a large or giant aneurysm of the internal carotid artery were treated by endovascular balloon occlusion of the internal carotid artery. In all three patients the aneurysm thrombosed completely. One patient became hemiplegic 12 days after carotid occlusion owing to hypoperfusion infarction. PMID- 7777088 TI - [Preconception consultation: a good idea?]. PMID- 7777089 TI - [National education for residents in surgery: specialist course Surgery; a report. Advisory Commission Specialist Course Surgery]. PMID- 7777090 TI - [Entering of patients in clinical-oncological trials: why not exclusive exclusion when inclusion is out of the question]. PMID- 7777091 TI - [Entering of patients in clinical-oncological trials: why not exclusive exclusion when inclusion is out of the question?]. PMID- 7777092 TI - [Good results in periodic screening in women with increased risk of breast cancer; retrospective study]. PMID- 7777094 TI - Improving care through your cancer program. PMID- 7777093 TI - Play ball! PMID- 7777095 TI - Another 'alphabet' group to affect your practice. PMID- 7777096 TI - Coronary artery bypass graft surgery in patients with poor left ventricular performance: results in a community hospital. Lincoln Heart Failure Treatment Program. PMID- 7777097 TI - Dangerous sequelae of epidural anesthesia in geriatrics. AB - These three cases demonstrate: (1) an epidural hematoma (case three); (2) a probable anterior spinal artery occlusion (case two); and (3) a low cord damage of obscure nature (case one). Three serious neurological sequelae after epidural anesthesia among the operated patients of one physician seems alarming. The three occurred within two years. These are published to direct attention to potential risks from epidural anesthesia in older patients. PMID- 7777098 TI - Effect of 1,25-dihydroxyvitamin D on the immune activity of peritoneal macrophages in continuous ambulatory peritoneal dialysis patients. PMID- 7777099 TI - On the progression of chronic renal disease. PMID- 7777100 TI - C1Q complexes with beta-2-microglobulin and amyloid P-component in sera of patients with dialysis-associated amyloidosis. AB - We studied complexes composed of C1q and beta 2-microglobulin (C1q.beta 2M) or serum amyloid P-component (C1q.SAP) in the sera of 38 patients receiving hemodialysis (HD) and 20 healthy control subjects using an enzyme-linked immunoassay. We also compared complex levels in HD patients with and without symptoms of HD-associated amyloidosis (HA). Serum C1q-beta 2M levels were significantly higher in HD patients without HA than in healthy control subjects and significantly higher in HD patients with HA than in HD patients without HA. Serum C1q.SAP levels were significantly lower in patients with HA than in those without HA. These results suggest that C1q.beta 2M may contribute to HA. PMID- 7777101 TI - Changes in circulating immune complex and charge distribution with upper respiratory tract inflammation in IgA nephropathy. AB - The circulating IgA class immune complex (IgA-IC) and its charge distribution, at the appearance of macroscopic hematuria and after tonsillectomy in patients with IgA nephropathy, were investigated in the present study. 3.5% polyethylene glycol precipitate (3.5% PEG-IgA) was used for IgA-IC detection and isoelectric focusing for its charge distribution. The level of IgA in 3.5% PEG-IgA, principally IgA1, and the proportion of anionic 3.5% PEG-IgA (isoelectric point, pl, 4.8-5.6) were significantly elevated in episodes of macroscopic hematuria with upper respiratory tract inflammation and with the appearance of macroscopic hematuria 1 day after tonsillectomy. Therefore, an increase in anionic IgA-IC (pl 4.8-5.6), principally IgA1, and the tonsils were considered to be concerned with the mechanism involved in the appearance of macroscopic hematuria. PMID- 7777103 TI - Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis. AB - Immunofluorescent study of urine sediments was performed to detect glomerular epithelial cell injuries using specific monoclonal antibody against podocalyxin, a glycoprotein that is prominently expressed on glomerular epithelial cells. Three kinds of structures (casts, granules and cells) were stained in urine sediments from various glomerular diseases. The presence of podocalyxin in urines was confirmed by absorption test, immunoelectron microscopy and Western blotting. Podocalyxin was detected in the urinary sediments of patients with various forms of glomerulonephritis, particularly those with acute onset. The amount of their urinary excretion apparently indicates the degree of the glomerular epithelial cell injuries in glomerular diseases. PMID- 7777102 TI - Sodium-lithium countertransport kinetics in IgA nephropathy: relation to plasma lipids and renal impairment. AB - We have investigated the activity and kinetics of sodium-lithium countertransport (SLC) in patients with IgA nephropathy and their relationship to plasma lipids. Standard SLC activity, the Michaelis constant (Km) and maximum velocity (Vmax) were measured in patients who had IgA nephropathy with either normal serum creatinine (IgA-NRF), or raised serum creatinine (IgA-IRF), and normal subjects (NC). The standard SLC activity was raised in hypertensive patients with IgA-NRF due to a raised Vmax in association with hyperlipidaemia. The Km was significantly lower and Vmax also tended to be lower in IgA-IRF. Km and Vmax were not different in IgA-NRF compared with the NC. There was no difference in the mean standard SLC activity between all three groups. The low Km and low Vmax resulted in a normal standard SLC activity being observed in IgA-IRF which is similar to the situation we have observed in a proportion of diabetic patients with nephropathy. The low Km in patients with IgA nephropathy may be due to inheritance associated with familial essential hypertension or to an acquired change of the kinetics related to a change in the environment of the plasma membrane during the development of renal impairment. PMID- 7777104 TI - Evaluation of red blood cell lipoperoxidation in hemodialysed patients during erythropoietin therapy supplemented or not with iron. AB - To investigate the effects of erythropoietin (rHuEPO) therapy supplemented or not with iron on hemolysis in hemodialysed patients (HD) we evaluated lipoperoxidation (LPO) by assaying (i) the red blood cell (RBC) antioxidant enzymatic system including superoxide dismutase (SOD), glutathione peroxidase, and catalase (Cat), (ii) RBC polyunsaturated fatty acids (PUFA) and (iii) malondialdehyde (MDA). Group 1 included 12 HD patients, group 2 had 7 HD patients with iron supplementation, group 3 comprised 12 HD patients with rHuEPO therapy and group 4 included 9 HD patients with both iron and rHuEPO therapies. No LPO was found in group 1 as regards MDA and PUFA levels. However, SOD and Cat activities were significantly elevated as compared to controls (p < 0.001). In the second group, a significant decrease in PUFA percentage was observed, particularly in 20:4(n-6) and 22:4(n-6) (the main ones involved in LPO) as compared to the other groups, whereas total MDA level was higher than that of the other groups. Similarly a decreased SOD activity was observed as compared to group 1 (p < 0.001), indicating its inactivation subsequent to an hyperproduction of reactive oxygen species through iron injection. In groups 3 and 4 no change was observed in MDA levels or PUFA percentages indicating no LPO. However, marked differences were observed in the enzymatic defense system. Particularly in group 3, SOD and Cat activities decreased when compared to group 1 (p < 0.001) whereas the association of erythropoietin and iron (group 4) increased the three enzymatic activities (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777105 TI - Serum guanidino compound levels in uremic pediatric patients treated with hemodialysis or continuous cycle peritoneal dialysis. Correlations between nerve conduction velocities and altered guanidino compound concentrations. AB - Serum levels of twelve guanidino compounds (GCs) and nerve conduction velocities were determined in a dialyzed renal insufficient pediatric population. Two dialytic groups were considered: one subjected to hemodialysis (HD, 11 patients) and one subjected to continuous cycle peritoneal dialysis (CCPD, 13 patients). Before HD, marked increases were found for guanidino-succinic acid (207 times), methylguanidine (> or = 67 times), argininic acid (24 times), creatinine and alpha-N-acetylarginine (18 times) and guanidine (> or = 14 times) when compared to controls. Important significant increases were still present after an HD session for guanidinosuccinic acid (49 times), methylguanidine (34 times), creatinine (7 times) and alpha-N-acetylarginine and guanidine (6 times). After HD, creatine, arginine and homoarginine were lower than in controls. All GCs, with the exception of creatine, decreased significantly after a single HD session with percentage decrease ranging between 40% (for arginine) and 77% (for guanidinosuccinic acid). Creatine decreased in a statistically nonsignificant manner by 48%. Marked increases were found in the CCPD group for guanidinosuccinic acid (114 times), alpha-N-acetylarginine (12 times), argininic acid (15 times), creatinine (22 times), guanidine (> or = 11 times) and methylguanidine (> or = 48 times). Concentrations of guanidinosuccinic acid before and after HD and in CCPD were comparable to those reported to be toxic in vitro and in vivo. No clinical or electrophysiological indications of polyneuropathy were observed in our population. Sensory and motor nerve conduction studies showed few abnormalities apart from a significant correlation between argininic acid concentration or guanidine levels and the peroneal nerve conduction velocity in the CCPD-treated group. PMID- 7777106 TI - Hereditary interstitial nephritis without basement membrane changes. AB - Hereditary interstitial nephritides are a heterogeneous group of disorders comprising medullary cystic disease, several varieties of Alport's syndrome and also one familial disorder with a distinct clinical syndrome and without characteristic ultrastructural glomerular basement membrane changes. Our family consisted of 11 members, 5 of which presented with renal dysfunction of varying degrees. Clinically, the affected siblings presented with long-standing hypertension, minimal proteinuria and no hematuria. All known causes of a secondary diffuse interstitial nephritis, Alport's syndrome and medullary cystic disease have been excluded. An HLA association is suggested between the affected and unaffected members of the family. Renal biopsy subsequently showed the typical features of a chronic interstitial nephritis without basement membrane changes. PMID- 7777107 TI - Effect of glucose infusion on the renal transport of purine bases and oxypurinol. AB - The effect of glucose infusion on renal handling of purine bases and oxypurinol was examined in 6 normal subjects. Five hundred milliliters of 1.1 M glucose solution were administered intravenously in 1 h. Fractional clearances of uric acid, xanthine and oxypurinol were significantly increased during glucose infusion, but that of hypoxanthine was not changed, while a 1-hour infusion of 500 ml of 1.1 M mannitol had no effect on the fractional clearances of purine bases and oxypurinol. These data indicate that the effect of glucose infusion on the renal clearances of uric acid, xanthine and oxypurinol was not related to osmotic diuresis but induced by glycosuria and/or hyperglycemia. Accordingly, the glycosuria- and/or hyperglycemia-induced decrease in the biological half-life of oxypurinol must be considered in the administration of allopurinol to gouty patients with uncontrolled diabetes mellitus. PMID- 7777108 TI - Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. AB - Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected. PMID- 7777109 TI - Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. AB - Thirteen patients in the predialysis phase of chronic renal failure (CRF) were treated with calcitriol (0.25 micrograms/day) and 12 with placebo. After 1 year of study, an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group (p < 0.001 and p < 0.01, respectively). We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF. This may be partly due to suppression of secondary hyperparathyroidism. PMID- 7777110 TI - Elevated serum levels of 3-deoxyglucosone, a potent protein-cross-linking intermediate of the Maillard reaction, in uremic patients. AB - 3-Deoxyglucosone (3-DG) has been identified as an intermediate of the Maillard reaction in vitro. We measured serum 3-DG levels using gas chromatography/mass spectrometry and found a marked elevation in serum 3-DG levels in uremic patients compared with healthy subjects. The uremic patients with diabetes showed significantly higher serum concentrations of 3-DG than those without diabetes. 3 DG was demonstrated to be a potent protein-cross-linking agent in the reaction with lysozyme, leading to browning, fluorescence formation and polymerization of the protein by formation of advanced glycation end products (AGE). The increase in serum 3-DG levels in the uremic patients suggests that 3-DG may be responsible for the development of uremic complications by promoting the formation of AGE. PMID- 7777111 TI - Liposoluble vitamins E and A in human renal cortex and renal cell carcinomas. AB - Vitamin E was quantified in renal cell carcinomas (RCC) and in 'intact' renal cortex, obtained from 31 patients subjected either to unilateral nephrectomy or to partial resection of the only kidney. Histologically, 14 tumors consisted predominantly of clear cells (group 1) and 17 of other cell types (group 2). In both groups, a significant increase in vitamin E concentration, as compared to the 'intact' cortex, was observed: 167.8 +/- 27.9 and 68.2 +/- 15.2 micrograms/g wet tissue weight (mean +/- SEM) for groups 1 and 2, respectively, versus 10.1 +/ 0.53 micrograms/g wet tissue weight for the cortex. Although the total lipid content was also increased in tumors (especially in group 1), the vitamin E concentration in tumor tissue, calculated per milligram of total lipids, proved to be much higher in both groups than in 'intact' cortex. A significant positive correlation was observed between vitamin E and total lipid content in group 1 and 2 carcinomas. It was also found that vitamin E accumulation in RCC is unlikely to be attributed to an enhanced lipid deposit in the tumor cells. Thus, in 8 tumors of group 2 the vitamin E levels were markedly enhanced although these tumors did not differ from the cortex in total lipid concentrations. Vitamin A content determined in 17 carcinomas, when calculated per milligram of total lipids, was the same as in 'intact' cortex. PMID- 7777112 TI - Morphological changes of the venous system in uremic patients. A histopathologic study. AB - Because of the decreased venous compliance in hypertensive dialysis patients, it was investigated whether their venous system exhibited structural abnormalities. Venous samples were taken during transplantation from the common and external iliac vein in 12 hypertensive and 6 normotensive uremic patients and from the distal inferior caval vein and the common iliac vein in 7 kidney donors and 5 autopsy patients without history of cardiovascular disease. The thickness of the venous media was significantly increased in hypertensive uremic patients as compared to controls, but did not differ between normotensive patients and controls. The quantity of medial collagen did not differ among the various groups. The smooth muscle content of the media was increased in 5 uremic patients (2 normotensive and 3 hypertensive patients), whereas almost no smooth muscle was observed in the media of controls. Intimal thickening was observed neither in uremic patients nor in controls. IN CONCLUSION: increased medial thickness in hypertensive dialysis patients could be an explanation for the decreased venous compliance previously found in these patients. PMID- 7777113 TI - Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients. AB - The value of serum transaminases (ST) in evaluating hepatitis B (HBV) and C (HCV) infection was studied in 217 hemodialysis (HD) patients and 804 normal controls. Mean serum aspartate aminotransferase (AST) was 22.3 (22.0-22.7) and 22.6 (21.6 23.6) IU/l or 0.371 (0.366-0.378) and 0.376 (0.36-0.393) mu kat/l in controls and HD patients, respectively (nonsignificant), while mean serum alanine aminotransferase (ALT) was 20.3 (19.9-20.7) and 16.3 (15.3-17.3) IU/l or 0.338 (0.331-0.345) and 0.271 (0.255-0.288) mu kat/l in these two groups (p < 0.001). However, both AST and ALT became significantly depressed in HD patients after adjusting for age, gender, HBV surface antigen (HBsAg) and anti-HCV. The usual practice of regarding AST and ALT as being 'abnormal' in evaluating viral hepatitis when they exceeded the upper reference range (40 and 46 IU/l or 0.666 and 0.766 mu kat/l in our laboratory) was then critically assessed by the receiver operating characteristic (ROC) curve. ROC analysis showed that ST was useless in detecting HBsAg, while the best cutoff point for detecting the presence of anti-HCV was 18 IU/l (0.3 mu kat/l) for AST and 16 IU/l (0.266 mu kat/l) for ALT in HD patients, respectively. These are considerably lower than the conventional criteria for an 'abnormal' ST. We conclude that ST are decreased in HD patients and that the cutoff value of ST for detecting HCV should be set at lower levels to enhance their diagnostic yield. PMID- 7777114 TI - The cytochemical profile of visceral mesothelium under the influence of lactated hyperosmolar peritoneal dialysis solutions. AB - Male albino mice had one daily intraperitoneal injection of 4.25 g/100 ml glucose concentration fluid for peritoneal dialysis at pH 5.0-5.2, for a period of 30 days. At the end of the experimental periods, mesothelial cell imprints were taken from the peritoneal layer of the anterior liver surface. Histochemical staining of imprints obtained from mice exposed to the peritoneal dialysis fluid showed a consistently increased activity of: (a) enzymes associated with the cell membrane: Na-K-ATP-ase, alkaline phosphatase and 5-nucleotidase; (b) cytoplasmic enzymes: acid phosphatase and cytochrome oxidase, and (c) a modestly increased activity of glucose-6-phosphatase. These changes, which are not far from those observed in activated mesothelial cells, suggest that exposure of mesothelial cells to high glucose concentrations of PD fluid is associated with increased production and disposal of energy to be used for maintaining the constancy of the cellular environment and, probably, for fuelling the transcellular transport of solutes of large molecular size. PMID- 7777115 TI - Renal magnesium wasting with hypercalciuria, nephrocalcinosis and ocular disorders. AB - We report a case of congenital magnesium-losing kidney with associated hypercalciuria and ocular derangements consisting of myopia, bilateral macular colobomata and bilateral papillary dysversion and hypoplasia. Our patient provides further evidence of the existence of an oculorenal syndrome associating abnormalities in the renal handling of magnesium and calcium, and myopia and chorioretinal disease. PMID- 7777116 TI - A case of renal vein thrombosis with posterior nut cracker syndrome. PMID- 7777117 TI - Acute renal failure secondary to antifibrinolytic therapy. PMID- 7777119 TI - Interleukin-2 therapy and renal enzyme excretion in patients with metastatic colorectal cancer. PMID- 7777118 TI - Accidental substitution of acidic concentrate for acetate in dialysis fluid concentrate: a cause of severe metabolic acidosis. PMID- 7777120 TI - Nephrotic syndrome associated with liver metastasis of rectal cancer. PMID- 7777121 TI - Acute piperazine encephalopathy in a hemodialyzed patient. PMID- 7777122 TI - Long-term persistence of improvement of renal anaemia in spite of discontinued erythropoietin treatment. PMID- 7777123 TI - Spontaneous perirenal hematoma as a rare complication of polyarteritis nodosa. PMID- 7777124 TI - Education and occupation as risk factors for dementia: a population-based case control study. AB - To further investigate the putative associations between education and dementia and between occupation and dementia, we conducted a population-based case-control study. Cases were all subjects affected by dementia ascertained through a prevalence survey conducted in the municipality of Appignano, Macerata Province, Italy. For each case (n = 48), we randomly selected 2 population controls residing in the same municipality and matched for age and sex (n = 96). Information regarding exposures was collected by nonmedical personnel during the first contact for the prevalence survey. Although we found a striking trend toward decreasing prevalence with increasing education, this association was suggestive but not significant after age and sex adjustment at case-control analyses (odds ratio for illiterates = 1.4; 95% CI 0.6-3.1). In contrast, we found a significant association between manual principal lifetime occupation and dementia using both unadjusted and adjusted analyses (odds ratio = 2.9; 95% CI 1.2-7.4). Our findings suggest that, although education and occupation are related, occupation is a stronger indicator of risk than education. PMID- 7777125 TI - Methods for a prevalence survey of neurological disorders in Junin, Buenos Aires, Argentina. AB - A two-phase prevalence survey of major neurological disorders was conducted in the city of Junin, Buenos Aires, Argentina. In phase 1, a sample of households was screened to identify persons who possibly had a disorder of interest. In phase 2, persons screened as positive in phase 1 were clinically examined by neurologists. This article describes the survey methods used, discusses related methodologic issues (e.g., the problem of false negatives), and presents demographic findings and attrition tallies. A brief account of the pilot investigations is also included as an appendix. PMID- 7777126 TI - Case-control study on the epidemiology of cluster headache. I: Etiological factors and associated conditions. Italian Cooperative Study Group on the Epidemiology of Cluster Headache (ICECH). AB - The etiological and physiopathological mechanisms of cluster headache (CH) are still largely unknown. The majority of the studies published on the possible risk factors and conditions associated with CH rely on either anecdotal observations or generalizations and have not been supported by serious epidemiological investigations. The aim of this case-control study was to evaluate the real association of life habits and general risk factors with CH. CH was associated only with cigarette smoking, head trauma and a positive family history for headache. Further epidemiologic studies are probably necessary in order to find clues to CH etiology. PMID- 7777127 TI - Magnitudes of neurological disorders in a farming town in Kyushu, Japan: frequency of neurological symptoms and signs. AB - We examined 1,270 elderly residents aged 60 years and over in a cross-sectional study of a standardized clinical examination to determine the frequency of 'abnormal' neurological findings in 27 randomly selected communities in the town of Mifune, Japan. The survey showed one or more neurological symptoms in 89.1%, and one or more signs in 94.4% of the examined elderly. Most of the symptoms and signs increased with age, especially after 70 years, indicating the importance of neurological afflictions in the community health of the elderly. PMID- 7777128 TI - Epidemiology of primary intracranial tumors in the Valle d'Aosta (Italy) during the 6-year period 1986-1991. AB - A total of 285 new cases of primary intracranial tumors (PIT: 178 cases, 62%) and secondary forms (107 cases, 38%) were detected by CT scan and MRI during a population-based study of the incidence rates of these neoplasms in the Aosta Valley (N.W. Italy: 114,325 residents in 1988) during the period 1986-1991. The PIT are discussed in this paper. Histological confirmation was obtained in 60%. Age- and sex-adjusted mean annual incidence rate for all PIT was 28.3/100,000 (men 21.7; women 28.1). The incidence rates by types were 9.7 for meningiomas (men 5.3; women 13.9), 9.1 for tumors of the neuroepithelial group (men 10; women 8.1), 3.7 for adenomas (men 2.6; women 4.6), and 1.9 for neurinomas (men 2.9; women 0.9). Incidence rate increased with age. Meningiomas comprised 37% of the PIT, followed by tumors of the neuroepithelial group (35%), adenomas (14%, neurinomas (7.3%) and malignant lymphomas (2.3%). The remaining subtypes were 4.6%. Our data showed a clearly higher incidence rate than in previous population based surveys. The differences were most marked in the meningioma group. The extensive use of CT scan and the more intensive case-finding could explain the differences. PMID- 7777130 TI - Expression of tyrosine hydroxylase in the aging, rodent olfactory system. AB - Tyrosine hydroxylase (TH) mRNA, immunoreactivity, and activity were examined as a reflection of dopamine expression in juxtaglomerular neurons intrinsic to the olfactory bulbs of young (6-month-old), middle aged (18-month-old), and aged (25- to 29-month-old) rats and mice. TH expression was maintained at levels observed in young animals in the olfactory bulbs of aged animals from two mouse strains, C57Bl/6JNia and C57Bl/6NNia, and one rat strain, an F1 hybrid between F344 and Brown Norway strains. The parental F344 rat strain exhibited reductions in TH expression of about 20% in 26- to 29-month-old animals as compared to 6- and 18 month-old rats. However, there was significant inter-animal variability. Some aged F344 rats had TH levels that were similar and others had activity levels that were 50% of those in young and middle aged animals. Neither the general condition of the animals nor the presence of adrenal tumors predicted the individuals with reduced TH expression. Olfactory bulb size, estimated from protein content, did not differ between rats and mice of different ages. In addition, expression of olfactory marker protein, a protein found primarily in mature olfactory receptor neurons, also was unchanged indicating the maintenance of afferent innervation. These data suggest that, in contrast to other brain dopamine systems, the expression of the dopamine phenotype is maintained in the aging olfactory bulb. PMID- 7777129 TI - Levels of stigmatization of patients with previously untreated epilepsy in northern Ecuador. AB - As part of a population-based study of epilepsy in northern Ecuador, 215 patients with epilepsy and 125 controls were given a questionnaire designed to elicit the degree of stigma associated with epilepsy. Evidence for stigma was also sought from local medical personnel. 144 patients and 98 controls were questioned again 12 months later at study completion to see whether their perceptions had changed. Both intellectual and physical abilities of people with epilepsy were regarded as low by controls, and this opinion did not change over the study period. Observations by medical personnel also suggested stigmatizing attitudes in the community. The number of patients reporting problems with their marriage or childbearing as a result of their epilepsy did not alter over the 12-month period, unlike their estimates of their own intellectual and physical capacities which had significantly improved. Conversely, although their expectations of employment outside the home had diminished, the reasons stated for this related to continuing epilepsy and not to the objections of fellow workers and employers. PMID- 7777131 TI - Age-related cochlear degeneration in senescence-accelerated mouse. AB - Age-related hair cell loss and strial atrophy were investigated in an accelerated senescence-prone strain, SAMP1 mice, and an accelerated senescence-resistant strain, SAMR1 mice. The loss of inner and outer hair cells in SAMP1 progressed more rapidly than that in SAMR1 with age. In both strains, areas of the loss of inner and outer hair cells were located mainly in the apex and base. Atrophy of the stria vascularis was observed in both strains, but in SAMP1 it appeared to increase earlier than in SAMR1. These results reveal that age-related hair cell loss and atrophy of the stria vascularis comparable to that in the human cochlea occur earlier and progress more rapidly in SAMP1 than in SAMR1. Hearing impairment in SAM may be due to a combination of sensory and strial presbycusis as well as to neural presbycusis, as reported previously. The morphological changes in the cochlea observed in SAMP1 and SAMR1 make these strains suitable for the study of the mechanisms of presbycusis. PMID- 7777132 TI - Protein kinase C activity, translocation, and conventional isoforms in aging rat brain. AB - Protein kinase C was studied in various brain areas in aging Wistar rats. Histone directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease in in vitro phosphorylation was detected in the membrane fraction of the cortex but after this age values remained stable. In hippocampal membranes, B-50 phosphorylation was increased in aged rats. PKC translocation was impaired in aged rats in both the cortex and the hippocampus. PKC alpha and beta mRNA decreased in the cortex between 3 and 8 months with no further decline in aged animals. Hippocampal mRNA for calcium-dependent PKC isoforms was not modified during aging, as assessed by Northern and in situ hybridization. Western blot analysis revealed a change in PKC gamma protein only, which was increased in hippocampal membranes from aged rats. The data indicate that the key PKC function that is impaired in aged rats is enzyme translocation irrespective of the brain area investigated. PMID- 7777133 TI - Age-related spatial reference and working memory deficits assessed in the water maze. AB - Aged rats have spatial memory deficits relative to young rats. The extent of these deficits in intermediate-aged rats is not well established. The present study examined the pattern of age-related changes in spatial reference and working memory in four ages of Fischer-344 rats. Place discrimination (PD) in the Morris water maze measured spatial reference memory. Repeated acquisition (RA), a discrimination in which the escape platform location varied from session to session, measured spatial working memory. Fischer-344 rats, 4 months, 11 months, 17 months, and 24 months of age, were tested. Compared to 4-month-olds, 24-month olds were significantly impaired on all six PD measures of performance, 17 months were significantly impaired on five PD measures, and 11 months were significantly impaired on only one PD measure. Only 24-month-olds had a significant working memory impairment in RA relative to 4 months. Reference and working memory measures were distinct as assessed by a principal components analysis. The results indicate a nonlinear age-related spatial memory decline in Fischer-344 rats from 4 to 24 months of age. PMID- 7777134 TI - Cholinergic binding sites in rat brain: analysis by age and cognitive status. AB - Age-related alterations in the density of cholinergic receptor binding and reuptake sites were examined in discrete forebrain regions of behaviorally tested rats using quantitative autoradiography. Neurochemical changes associated with chronological age alone were distinguished from memory-dependent alterations by correlating density of binding sites with performance in the Morris water maze task. An initial analysis of tritium quenching indicated no reliable differential quenching in the study population. Modest age-related reductions in selected subtypes of cholinergic binding sites in basal forebrain, basal ganglia, and thalamus were observed. However, these reductions were not correlated with a spatial memory deficit. In contrast, no significant changes in the analysis by chronological age were detected for the density of [3H]hemicholinium binding to high affinity choline uptake sites or [3H]pirenzepine binding to M1 receptors in any brain region but strong correlations were found between behavioral performance of aged rats and density of these sites in dorsal hippocampal subfield CA3 and dentate gyrus. These findings indicate the value of combined neurobiological/behavioral assessment. PMID- 7777135 TI - Mesostriatal dopamine markers in aged Long-Evans rats with sensorimotor impairment. AB - Changes in the mesostriatal dopamine system associated with normal aging are observed in both human and laboratory animals, but the specific behavioral consequences of these nonpathological changes are largely unexplored. The present study (a) assessed the effects of normal aging on markers for the mesostriatal dopamine system, and (b) examined the relationship of age-related changes in this system to decline in reaction time performance. Decreased levels of midbrain dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were observed in the aged rats as compared to young, but there was no evidence for age-related changes in the density of D1 or D2 receptor binding or the density of dopamine uptake sites. Some differences were observed when the aged rats were grouped according to reaction time performance. Aged RT-unimpaired rats exhibited higher density of D1 binding in rostrodorsal striatal patch areas, but lower overall levels of DA. In caudal striatum, aged RT-unimpaired rats exhibited lower DA and higher DOPAC levels. PMID- 7777136 TI - Anticonvulsants attenuate amyloid beta-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology. AB - Increasing evidence supports the involvement of amyloid beta-peptide (A beta) and an excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. However, approaches aimed at preventing A beta toxicity and neurofibrillary degeneration are undeveloped. We now report that anticonvulsants (carbamazepine, phenytoin, and valproic acid) can protect cultured rat hippocampal neurons against A beta- and glutamate-induced injury. Each of the anticonvulsants attenuated the elevation of intracellular free calcium levels [(Ca2+)i] elicited by A beta or glutamate suggesting that their neuroprotective mechanism of action involved stabilization of [Ca2+]i. These compounds were effective at clinically relevant concentrations (carbamazepine, 100 nM-10 microM; phenytoin, 100 nM-1 microM; valproic acid, 100 nM-100 microM). The anticonvulsants suppressed glutamate-induced alterations in tau and buiquitin immunoreactivities. Compounds that stabilize [Ca2+]i may afford protection against the kinds of insults believed to underlie neuronal injury in Alzheimer's disease. PMID- 7777137 TI - Age-related levels of GABA/benzodiazepine binding sites in cerebrum of F-344 rats: effects of exercise. AB - We examined gamma-aminobutyric acid (GABA), benzodiazepine and convulsant sites of postsynaptic GABA/benzodiazepine receptors (GBZR) in cerebral membranes of inbred Fischer 344 male rats as a function of age. In aged rats (23 to 24 months), the benzodiazepine binding site as determined by [3H]flunitrazepam was 47% and 43% lower than corresponding values in young adult (3 to 4 months) and mature (10 to 12 months) rats, respectively. The decrease was due to the loss of binding density rather than a change in affinity. No statistically significant age-related changes in [3H]muscimol binding were observed when 5 nM or 40 nM labeled muscimol were used. GABA produced a dose-dependent stimulation of flunitrazepam binding in all age groups, but the maximum stimulation in aged animals was significantly higher (24%) than in young and mature animals. The [35S]TBPS binding site, the convulsant site of GABA/benzodiazepine receptors, was unaffected with age. We also studied the effects of exercise on GBZR binding sites of aged rats. The decline of flunitrazepam binding sites and the high sensitivity of flunitrazepam binding to regulation by GABA in aged animals were reversed by 8 to 10 weeks of endurance exercise. Endurance exercise did not have any significant effect on muscimol or TBPS binding sites. Results suggest that there are aged-related alterations of GBZR binding sites and that these modifications can be reversed by exercise. PMID- 7777138 TI - Hypothalamic-pituitary-adrenal system function in patients with Alzheimer's disease. AB - The neuropathologic hallmarks of Alzheimer's disease (AD) are very prominent in the hippocampus, a brain site which is pivotal for the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Thus, the combined dexamethasone suppression/CRH-stimulation-test outcome in patients with AD was compared to that of healthy elderly controls to assess--with a more refined neuroendocrine challenge procedure--HPA function in AD. Cortisol secretion after dexamethasone (DEX) pretreatment and before CRH was increased in Alzheimer's patients and 21% of this group were DST-nonsuppressors. None of the healthy control subjects escaped DEX-induced suppression of cortisol. However, after additional CRH administration, AD patients released significantly less cortisol and ACTH than the control subjects. No correlations were found between any of the endocrine parameters and degree of severity of dementia. It is concluded that the DST part of the DEX/CRH test better reflects glucocorticoid feedback disturbances, probably at a suprapituitary level. The CRH part of the DEX/CRH-test outcome might indicate the loss of endogenous CRH-Arginine-Vasopressin (AVP) synergism of the HPA system of these patients. PMID- 7777139 TI - Color image analysis in neuroanatomical research: application to senile plaque subtype quantification in Alzheimer's disease. AB - Many problems in neuroanatomy and neuropathology require the collection of large data sets and would benefit from a method that allows for rapid quantitative analysis to be carried out on a routine basis. An example is the quantification and subtype classification of the number of senile plaques in post-mortem Alzheimer's disease tissue. A method to reliably automate the analysis of plaques and their underlying subtypes would allow more rigorous and quantitative correlations to be investigated. Computer assisted image analysis of data typically utilizes gray scale images. These methods, however, are only applicable to quantification of objects labeled with a single marker. We sought to extend this type of analysis to double-labeled tissue sections so we could quantify dual labels separately based on their peroxidase color characteristics, analyze the resultant occurrence of overlap between the two labels, and classify senile plaques into discrete subtypes. We present a method for semi-automated color image analysis which allows one to identify separate labels based on histogram mapping of hue, saturation and value as well as apply overlapping feature detection algorithms. The technique is application driven, so that a trained observer can set threshold or object criteria and verify the desired results. These methods were able to yield total "amyloid load" and "dystrophic neurite load" values, generate plaque histograms based on total size, and subtype plaques into diffuse/primitive and neuritic/classical categories. By adjusting feature criteria, we were able to achieve promising agreement (Fisher's R to Z correlation of 0.94) between a human observer and the computer algorithm in the classification of plaque subtypes using three AD cases. PMID- 7777140 TI - Influence of norepinephrine, acetylcholine, and their blockers on the activity of cortical neurons in goal-directed behavior. AB - The neurochemical mechanisms of the central organization of sequential stages in the formation of a goal-directed behavioral act were investigated by means of the microiontophoretic application of biologically active substances to individual neurons of the cerebral cortex of cats. It was demonstrated that the dynamics of the discharge activity of the neurons at particular stages of the behavioral act exhibited a contradictory character when neuromediators and their antagonists were applied. At the same time, differences in the impulse activity were more pronounced against the background of the application of propranolol and atropine than of norepinephrine and acetylcholine. PMID- 7777141 TI - Long-term posttetantic changes in the reaction of neighboring neurons in microsegments of the cat motor cortex. AB - The long-term postsynaptic changes of mono- and polysynaptic reactions of neighboring neurons of the MC were investigated following conditioning tetanization of different afferent inputs. Modifiable synapses were found both in the cells investigated and in local neuronal circuits which included the cells, i.e., possibly in interneurons. Alternating and concurrent conditioning of thalamocortical and corticocortical input showed that, depending upon the modality of the conditioned input, the tetanization parameters, the character of the distribution of the afferents, as well as on the character of local circuits which include excitatory and inhibitory interneurons, the effectiveness of synaptic inputs to neighboring neurons varies diversely, as a result of which a specific pattern of interneuronal connections forms in a microsegment of cortex, a pattern which may be maintained over the course of tens of minutes. It was found that modifiable synapses of different types may function simultaneously in one and the same micronetwork. The investigation may be of interest in developing models of memory and learning. PMID- 7777143 TI - Spontaneous potentiation of focal potentials of the CA1 field in long-surviving hippocampal slices of the rat in the absence of electrical stimulation. AB - The changes in the efficiency of the synaptic transmission in the Schaffer collaterals-field CA1 neurons pathways following prolonged deprivation of afferentation, the cessation (up to four hours) of stimulation of the tested input with brief series of tests every hour (the control afferent inputs, were stimulated throughout the entire experiment at a frequency of 0.05/sec), were investigated in surviving slices of the hippocampus of rats. The evoked focal potentials, population spikes (PS) and population excitatory postsynaptic potentials (pEPSP) were recorded. The prolonged cessation of stimulation led to a significant (p < 0.001) increase in the amplitude of the PS (up to 208% in relation to the baseline level). This phenomenon of potentiation was specific in relation to input and exhibited the properties of "E-S potentiation". A hypothesis is advanced regarding the association of mechanisms responsible for the development of "deprivational" potentiation and of the late phase of long term posttetanic potentiation. PMID- 7777144 TI - Basal and luliberin-stimulated secretion of gonadotropins in ovariectomized rat females with streptozotocin-induced diabetes. PMID- 7777142 TI - Dynamics of the reactivity of cortical neurons to the repeating isolated action of L-glutamate and acetylcholine. AB - A comparative analysis of the probability, directionality, and intensity of the changes in the average frequency of the baseline (BIA) and L-glutamate-induced (GlIA) and acetylcholine-induced (AChIA) impulse activity of individual neurons of the sensorimotor cortex of unanesthetized rats showed that the reactions to Gl are most variable; this is expressed in a significantly higher percent of neurons with potentiation of responses to Gl as compared with the proportion of cells which manifested an increase in the AChIA in the course of 20 applications of the mediators. As a result of 100 applications, the GlIA decreases most frequently; also, the degree of decrease in GlIA over the entire duration of the testing exceeds the degree of decrease in AChIA. It is more characteristic of ACh than of Gl to increase the level of BIA in the periods between the reactions to ACh, while in the case of repeated application of Gl, dynamics of decrease in BIA are characteristic. The results are discussed from the perspective of a possibly different functional role of the glutamatergic and cholinergic neuromediator systems in the cerebral cortex in the process of formation of the dynamics of neuronal activity during learning. PMID- 7777145 TI - Analysis of hypothalamohypophyseogonadal interrelationships in female rats in experimentally-induced diabetes. PMID- 7777146 TI - Reflection of internal and external determinants of behavior in the neuronal activity of the neostriatum of monkeys. AB - It has been demonstrated that some neurons of the neostriatum of monkeys (Macaca nemestrina) participate in supporting the reaction of the animal to the appearance of standard situations in which a decision is made on the basis of already existing skills. Other neurons (primarily non-baseline active), by contrast, are activated in nonstandard situations, when the use of existing skills is ineffective. It is hypothesized that their activity is associated with the shift of the animal to a different activity which consists in the rejection of the use of existing skills for the formation of new skills. PMID- 7777147 TI - Influence of the blockade of D2 dopamine receptors of the cat neostriatum on the baseline activity and saccadic eye movement-associated reactions of neurons of the reticular portion of the substantia nigra. AB - The activity of neurons of the reticular portion of the substantia nigra before and after the microinjection of haloperidol (25 micrograms/5 microliters) into the head of the caudate nucleus on the ipsilateral side was investigated under chronic experimental conditions in cats, using the extracellular microelectrode pickup technique. A significant (p < 0.05) increase, from 34 to 61%, of neurons with the burst type of spontaneous activity was established after the injection of haloperidol. A significant increase in the ratio of the number of excitatory responses to inhibitory responses, from 0.04 to 0.4, was identified among the reactions associated with saccadic eye movements following the microinjection of haloperidol. The number of orienting saccades in response to the visual stimulus decreased against this background from 58 to 37%. The identified changes are regarded as a result of the disinhibition of GABAergic neurons of the reticular portion of the substantia nigra under the influence of the blockade of D2 dopamine receptors of the neostriatum. PMID- 7777148 TI - Structure of neuronal activity of the caudate nucleus of monkeys during decision making and the realization of the motor program in different variants of a delayed spatial choice task. AB - In this paper the results of investigations of the participation of caudate nucleus neurons in the decision-making process and the process of organization of the program of a future motor response during the performance by Macaca mulatta monkeys of a delayed spatial choice tasks of varying degrees of complexity are presented. The presence in the caudate nucleus of spatially selective neurons, which are subdivided into two groups, was established: the position of conditional signals is reflected in the activity of one of the groups, and the direction of the future motor response is reflected in the activity of the other. The decision-making process is reflected in the impulse activity of neurons of the head of the caudate nucleus in two of its aspects: as the formation or choice of a specific motor program (spatially selective activity) and as a transitional factor from the instructive to the executive phase of the behavior. PMID- 7777149 TI - Influence of dilantin on the reactions of neurons of the visual cortex and the behavior of rabbits during learning. AB - Changes in behavior in response to light flashes, the conditional stimulus of a defense reflex, were not observed following the administration of dilantin, a preparation which attenuates posttetanic potentiation, in rabbits with preliminarily developed defense and inhibitory conditioned reflexes; weak disinhibition of movements appeared in response to the action of flashes against the background of a conditional inhibitor. The similarity of the reactions of the neurons of the visual cortex to light flashes, the CS, with the responses to their joint action with the reinforcement, did not weaken in the majority of instances, while in several neurons, it intensified. The differences in the responses to reinforced and inhibitory light flashes did not disappear following the administration of dilantin, but they attenuated in some of the neurons due to filling of the inhibitory pause with impulses. The results obtained make it possible to draw the conclusion that posttetanic potentiation does not participate in the maintenance of developed conditioned reflexes. PMID- 7777150 TI - Afferent and efferent mechanisms of the intensification of neostriatal cholinergic activity. AB - Data have been obtained in chronic experiments on 34 dogs, based on an instrumental defense reflex model associated with the maintenance of a specific posture, which suggest that activation of the cholinergic system of the neostriatum leads to a large number of changes in both the sensory and the motor spheres. The influences on motor behavior, observed mainly through effects on the cholinergic system of the contralateral caudate nucleus, reside in the intensification of the tonic constituent of movement, in inhibition of the phasic component of movement, and restriction of locomotor activity, all the way up to complete shutdown. The influences on sensory mechanisms, observed both through ipsi- and contralateral effects on the cholinergic system of the neostriatum, reside in an improvement of the differentiation of significant signals and are evidently through inhibition of the nonspecific afferent stream. Data are presented on the important role of the cholinoreactive systems of the CM-Pf complex of the thalamus in the intensification of the cholinergic activity of the neostriatum. PMID- 7777151 TI - Disturbances in cognitive activity and its neuropharmacological correction in structural-functional insufficiency of the head of the caudate nucleus in cats. AB - The participation of the head of the caudate nucleus in the organization of praxis, perception, gnosis, and "ideational operations" has been demonstrated. The broad spectrum of dysfunctions observed in the presence of caudate insufficiency was eliminated by a specific set of psychotropic preparations acting on classical neuromediator systems of the brain of cats. PMID- 7777152 TI - Role of dopaminoreactive systems of the cortex and the neostriatum in the organization of situational conditioned reflexes. AB - The results of experiments on dogs with dysfunction of the dopaminoreactive system of the brain suggest the nonidenticality of its different divisions (cortical, striatal, mesencephalic) in the organization of situational conditioned reflexes. It was demonstrated that the nigrostriatal system is involved to a greater degree in the spatial analysis of signals, while the mesocortical system is more involved in the analysis of their biological significance. The dopaminoreactive system of the caudate nucleus is associated to a greater degree with the realization of cognitive, while that of the putamen is associated with the realization of motor programs of situational conditioned reflexes. The thesis of the necessity of the coordinated functioning of the DA reactive systems for the organization of goal-directed behavior is substantiated. PMID- 7777153 TI - A metabolic map of cytochrome oxidase in the rat brain: histochemical, densitometric and biochemical studies. AB - To examine brain patterns of metabolic and functional activity, the distribution of cytochrome oxidase, a mitochondrial enzyme marker for neuronal functional activity, was mapped throughout the rat brain. Mapping was done qualitatively by enzyme histochemistry of brain sections cut in three planes (coronal, sagittal and horizontal), and quantitatively by optical densitometry of stained sections and by biochemical assays of brain tissue homogenates. Activity of the enzyme was distributed in characteristic patterns and amounts that differed among various neural pathways, brain nuclei, cerebral cortical areas and layers, and neuron types. Gray matter essentially always had higher enzyme activity than did white matter, by a factor of eight- to 12-fold. Among different neural pathways, cytochrome oxidase activity was relatively high in special sensory, somatosensory and motor systems, and was relatively low in associative, limbic, autonomic and visceral regulatory systems (though exceptional areas were present). Among 11 different neuron types, nearly a two-fold range of histochemical staining intensities was observed, with the darkest staining in neurons of the mesencephalic trigeminal nucleus. The observed patterns of cytochrome oxidase activity were mostly similar to the patterns of 2-deoxyglucose uptake seen previously [Schwartz W. J. and Sharp F. R. (1978) J. comp. Neurol. 177, 335-360; Sokoloff L. et al. (1977) J. Neurochem. 28, 897-916] in conscious, "resting" animals, though some differences were found. For example, whereas 2-deoxyglucose uptake was about three-fold higher in gray matter than in white matter [Sokoloff L. et al. (1977) J. Neurochem. 28, 897-916], cytochrome oxidase activity was about eight- to 12-fold higher. This and other discrepancies probably reflect basic technical differences between these two methods. Compared to 2 deoxyglucose, cytochrome oxidase is more specific for oxidative rather than glycolytic metabolism, and more reflective of overall neuronal functional activity occurring over longer time periods lasting hours to weeks, rather than minutes. The anatomical resolution of cytochrome oxidase histochemistry is also finer than that of 2-deoxyglucose autoradiography, extending to the electron microscopic level. The metabolic map of cytochrome oxidase activity reveals patterns of normal brain function, and may be useful as a baseline for comparison in studies of brain disease, development, ageing and plasticity. PMID- 7777154 TI - Abdominal vagal stimulation excites bulbospinal barosensitive neurons in the rostral ventrolateral medulla. AB - We used extracellular recordings to examine the central pathway whereby electrical stimulation of abdominal vagal afferents elevates arterial pressure in the rabbit. Bulbospinal neurons in the rostral ventrolateral medulla were identified by antidromic activation from the dorsolateral funiculus of the thoracic spinal cord. Their barosensitivity was assessed by their response to intravenous phenylephrine and by their cardiac cycle-related rhythmicity. We used peristimulus histogram procedures to assess the effect of electrical stimulation of abdominal vagal afferents on the discharge rate of these neurons. Electrical stimulation (one to three pulses) activated 98 of 123 neurons tested (80%), had no effect on 22 neurons (18%) and inhibited the remaining three neurons. Latency to peak excitation was 228 +/- 3 ms, indicating that the conduction velocity of the vagal afferents was about 0.6 m/s, in the unmyelinated fibre range. Lower oesophageal distension with a balloon excited 22 of 48 neurons (46%), inhibited 12 neurons (25%) and had no effect on the remaining 14 cells (29%). Vagally induced excitation was reduced by aortic depressor nerve stimulation in nine of 13 neurons. Lightly touching the animal's back and legs had no effect on 56 of 60 neurons. Nociceptive stimuli failed to affect 47 of 60 neurons tested. No excitation was seen with electrical stimulation of the sciatic or central ear nerves. Our study identifies a robust excitatory input from the abdominal vagus to bulbospinal barosensitive neurons in the rostral ventrolateral medulla. Relevant physiological stimuli include lower oesophageal distension. The pathways may be relevant to cardiovascular changes which accompany upper gastrointestinal function. PMID- 7777155 TI - Dopamine and complex sensorimotor integration: further studies in a conditioned motor task in the rat. AB - Rats were trained to depress a lever and wait for the onset of a light stimulus, occurring after four equiprobable and variable intervals. At the stimulus onset, they had to release the lever within a reaction time limit for food reinforcement. This paradigm required time estimation of the various intervals and high attentional load for correct performance. Following activation of the dopaminergic transmission after systemic injection of d-amphetamine (0.6 and 0.8 mg/kg) or intrastriatal injection of dopamine (2.5 microgram/microliters), the rat's performance was impaired. Compared with control animals, the performance deficits were expressed as an increased number of premature lever releases before the conditional stimulus onset ("premature responses") and decreased reaction times. Indeed, the reaction times distribution was shifted to the left towards shortened reaction times. Although the number of premature responses was increased, the time estimation of the four different equiprobable intervals was not disturbed after stimulation of dopaminergic activity. A delay-dependent shortening of reaction times as a result of the conditional probability of the stimulus occurrence (i.e. reaction times are shorter as the duration of the delay increases) was found in control and drug sessions, indicating that the animals were still able to prepare their motor response (lever release) even after overstimulation of the dopaminergic transmission. In contrast, blocking dopamine receptors with the selective D2 antagonist raclopride was found to induce opposite effects on the reaction time performance. The number of delayed responses (i.e. occurring with a latency > 600 ms) was found to be significantly enhanced. Furthermore, the reaction times distribution showed a shift of the values to the right revealing a general tendency to lengthened reaction times. These results indicate that a "critical level" of dopamine activity (neither too low nor too high) in the striatum is necessary for a correct execution of the movement in a conditioned motor task with temporal constraint. Moreover, while delayed responses might reflect a motor impairment, anticipatory responses might reflect a "motor facilitation" revealed by a higher level of motor readiness, without disturbing time estimation nor attentional processes. PMID- 7777156 TI - Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine. AB - The repeated administration of amphetamine in rats produces behavioral sensitization which is characterized either by a progressive enhancement of the locomotor activity induced by the drug or by an enduring behavioral hypersensitivity to the drug after the cessation of the treatment. Some authors have suggested that the action of amphetamine at the level of the nucleus accumbens is responsible for the expression of behavioral sensitization, whereas the action of amphetamine at the level of the dopamine cell bodies in the ventral tegmental area induces some changes responsible for the initiation of the phenomenon. The present study fully tested this hypothesis. In two separate experiments, the effects of different doses of amphetamine repeatedly administered in the ventral tegmental area or in the nucleus accumbens were tested on the later behavioral reactivity to the administration of amphetamine in the nucleus accumbens. Independent groups of rats received five repeated administrations (one injection every other day) of different doses of amphetamine either in the ventral tegmental area (0, 1, 2.5, 5 micrograms/0.5 microliters per side) or in the nucleus accumbens (0, 1, 3, 10 micrograms/l microliters per side). Two days following the last intracerebral amphetamine injection, each group received a phosphate buffer solution challenge directly into the nucleus accumbens followed two days later by an amphetamine challenge (1 microgram/l microliters per side) in the nucleus accumbens and two days later by a peripheral challenge with amphetamine (0.5 mg/kg, s.c.). Locomotor responses were recorded following each injection. Results showed that injections of amphetamine into the nucleus accumbens induced a dose-dependent increase in locomotor activity which remained identical with the repetition of the injections. No difference between the different intra-accumbens pretreated groups was observed following the diverse phosphate-buffered saline solution and amphetamine challenges. In contrast, intra-ventral tegmental area administration of amphetamine did not produce any modification of locomotor activity. However, whereas no difference between the differently pretreated groups was observed following phosphate buffered saline administration into the nucleus accumbens, a potentiation of the locomotor response to a challenge dose of amphetamine into the nucleus accumbens was observed which was dependent on the dose of amphetamine pretreatment into the ventral tegmental area. Similar potentiation was observed following peripheral challenge with amphetamine. Finally, cross-sensitization was observed when a challenge dose of cocaine (10 micrograms/1 microliter per side) was injected into the nucleus accumbens, as well as when a peripheral challenge dose of morphine (2.5 mg/kg, s.c.) was administered to the ventral tegmental area-pretreated groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777158 TI - Distribution of preproenkephalin messenger RNA in the basal ganglia and limbic associated regions of the monkey telencephalon. AB - We studied the distribution of preproenkephalin messenger RNA in the monkey forebrain, using a free-floating method for in situ hybridization histochemistry. Autoradiographs reveal a high level of specific hybridization to preproenkephalin messenger RNA in the monkey striatum and forebrain regions. In the monkey striatum, the distribution of preproenkephalin messenger RNA is heterogeneous. There is variation in the general labeling pattern between regions of the striatum. For example, a particularly densely labeled area of preproenkephalin messenger RNA is observed in the ventral part of the caudal putamen. In addition, at the macroscopic level, there are patches of specific hybridization intermingled with areas containing less specific labeling. This forms a mosaic like pattern. At the microscopic level, densely labeled individual cells are found among those with little or no specific labeling. Adjacent sections, processed for in situ hybridization and immunohistochemistry, show some correlation between the perikarya containing preproenkephalin messenger RNA and enkephalin-positive fibers in the striatum. Specific hybridization to preproenkephalin messenger RNA is evident throughout the cortical mantle, primarily concentrated in layers 2 and 3. Particularly high levels of preproenkephalin messenger RNA are found in specific limbic-associated cortices, including the piriform allocortex, the agranular area of the orbitofrontal cortex, the agranular insular cortex and the caudal field of the entorhinal cortex. Specific labeling is also present in the granular cell layer of the dentate gyrus and in the amygdaloid complex. This study reveals heterogeneous distribution of dense preproenkephalin messenger RNA in the basal ganglia and high levels of preproenkephalin messenger RNA in specific limbic-associated regions of the monkey telencephalon. PMID- 7777157 TI - Quinolinic acid-induced increases in calbindin D28k immunoreactivity in rat striatal neurons in vivo and in vitro mimic the pattern seen in Huntington's disease. AB - In Huntington's disease striatal neurons undergo marked changes in dendritic morphology and coincidently exhibit an increase in immunoreactive calbindin D28k (calbindin), a cytosolic calcium-binding protein which is highly abundant in these neurons. Previous studies in the rat striatum have shown that excitotoxic injury, which is linked to a rise in intracellular Ca2+, mimics many of the neurochemical and neuropathological characteristics of Huntington's disease. We speculated, therefore, that the apparent increase in calbindin labeling in Huntington's disease spiny neurons may signal the response to an excitotoxic process. To investigate this possibility, we compared the cellular features of calbindin immunoreactivity in grade 1-4 Huntington's disease cases with those seen in rat striatal neurons in vivo and in vitro following treatment with N methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid. In human post mortem control cases calbindin immunoreactivity was seen primarily in the somata and proximal dendrites of striatal neurons. In the Huntington's disease cases, calbindin labeling was markedly increased throughout the second and third order dendrites and in spines, and this change was more prevalent in advanced cases (grades 3-4). In the rat brain, two weeks after intrastriatal injection of quinolinic acid (6-20 ng), surviving medium-spiny neurons in the transition zone around the lesion core exhibited a marked increase in calbindin immunoreactivity similar to that seen in Huntington's disease spiny neurons. In more peripheral areas away from the lesion and on the contralateral unlesioned side, calbindin immunostaining was confirmed to somata and proximal dendrites. In situ hybridization histochemistry with an 35S-labeled oligonucleotide probe showed no change or a decrease in calbindin mRNA levels in neurons within the transition zone, suggesting that the observed increase in calbindin staining was not the result of increased transcription. In 12 day old postnatal striatal cultures, 2-6 h exposures to quinolinic acid (0.5 mM) significantly increased the length of neurites exhibiting calbindin immunoreactivity when compared to untreated controls. This effect was blocked by the selective NMDA receptor blocker (+/-)-2 amino-5-phosphonopentanoic acid (AP-5), indicating that an NMDA receptor-mediated mechanism contributed to the change in staining pattern. Results in rats suggest that the subcellular redistribution of calbindin immunoreactivity observed in Huntington's disease spiny neurons may be related to an NMDA receptor-induced excitotoxic process. An increased availability of calbindin protein at dendrites and spines may reflect a greater demand for Ca2+ buffering precipitated by an abnormal rise in in intracellular Ca2+. PMID- 7777159 TI - D1- and D2 dopaminergic receptors in the developing cerebral cortex of macaque monkey: a film autoradiographic study. AB - Film autoradiography was used to study the distribution of D1- and D2 dopaminergic receptors in the prefrontal association, somatosensory, primary motor and visual regions in the developing cerebral cortex of macaque monkeys. D1 receptors were labeled with [125I]SCH23982, while D2 sites were visualized with [125I]epidepride. D1- and D2-dopaminergic sites are already present in all cortical areas at embryonic day 73, the earliest age observed in this study. In contrast to the adult cortex, where D1 and D2 receptors have different distributions, during development there are substantial similarities in the laminar patterns of these sites. In particular, both D1 and D2 receptors tend to concentrate in the marginal zone and layer V of the developing cortical plate. The autoradiograms also show a high density of D1-dopaminergic sites in the transient ventricular and subventricular zones, where cortical neurons are generated. Although there is a significant rearrangement of the early laminar patterns, the adult distribution of both dopaminergic receptors in most cortical areas is achieved prenatally, soon after all cortical neurons assume their final positions. An early presence in the cerebral wall, a high density in the proliferative zones and fast maturation of the laminar distribution suggests that dopaminergic receptors may be involved in the regulation of cortical development. PMID- 7777160 TI - Tyrosine hydroxylase- and dopamine-beta-hydroxylase-positive neurons and fibres in the developing human cerebellum--an immunohistochemical study. AB - Six human fetuses of gestational ages 16-28 weeks were employed. The immunocytochemical avidin-biotin-peroxidase complex method combined with the silver Bodian technique was used to evaluate the presence of tyrosine hydroxylase and dopamine-beta-hydroxylase neurons and afferent and efferent fibres in the cerebellum during development. Our results illustrated that by 16-18 weeks, immunoreactivity of the Purkinje cells and the granule cells was evident. By 23 weeks, the positive Purkinje cells were tightly packed together and the perinuclear granules began to extend into the processes. The positive cells next to Purkinje cells were the basket cells and stellate cells. By 26-28 weeks, all positive cells increased in number and size. Mossy and climbing fibres appeared early in development (16-18 weeks of gestation) and were seen synapsing with the positive granule cells. At the same time, some parallel fibres were observed. At later stages, the tyrosine hydroxylase- and dopamine-beta-hydroxylase-positive Purkinje cells were surrounded by abundant climbing fibres, while parallel fibres were also evident in the molecular layer. In the deep cerebellar nuclei, positive tyrosine hydroxylase and dopamine-beta-hydroxylase neurons were present by 16-18 weeks of development. Those in the dentate nucleus were more polymorphic but smaller in size. Some afferent fibres were also spotted around 16-18 weeks of gestation and their numbers increased later. Positive efferent fibres were present by 26 weeks. All these observations point to an early presence of tyrosine hydroxylase and dopamine-beta-hydroxylase components in cerebellar development. PMID- 7777161 TI - 192 immunoglobulin G-saporin produces graded behavioral and biochemical changes accompanying the loss of cholinergic neurons of the basal forebrain and cerebellar Purkinje cells. AB - Immunolesions of the cholinergic basal forebrain were produced in rats using various intraventricular doses of the immunotoxin 192 immunoglobulin G-saporin: 0.34, 1.34, 2.0, 2.7 and 4.0 micrograms/rat. A battery of behavioral tests, chosen on the basis of reported sensitivity to conventional medial septal or nucleus basalis lesions, was administered. Dose-dependent impairments were found in acquisition, spatial acuity and working memory in the water maze. Dose dependent hyperactivity in the open field and in swimming speed was observed. The highest dose group (4.0 micrograms) exhibited motoric disturbances which were particularly apparent in swimming and in clinging to an inclined screen. Response and habituation to acoustic startle were diminished in the three higher dose groups. Histological results from acetylcholinesterase and low-affinity nerve growth factor receptor staining showed that the lesion was selective for cholinergic neurons bearing p75 nerve growth factor receptors in the basal forebrain nuclei. However, some Purkinje cells in the superficial layers of the cerebellum were also destroyed at the higher doses of immunotoxin. The activity of choline acetyltransferase, used as a marker of cholinergic deafferentation in regions innervated by the basal forebrain nuclei, was decreased with increasing doses to a plateau level of about 90% (average depletion) for the two highest dose groups. These two groups were the only ones to exhibit consistent and severe behavioral impairments on all behavioral tests performed. Thus, for a relatively selective cholinergic basal forebrain lesion, almost a 90% reduction in choline acetyltransferase activity is needed to produce substantial behavioral deficits. It appears that either a considerable safety factor exists or robust compensatory mechanisms can ameliorate behavioral deficits from a major, but incomplete loss of cholinergic basal forebrain innervation. PMID- 7777163 TI - c-fos antisense oligodeoxynucleotide increases formalin-induced nociception and regulates preprodynorphin expression. AB - Rats, receiving an intrathecal pretreatment of oligodeoxynucleotide complementary to c-fos mRNA (antisense), showed no increases in Fos protein or preprodynorphin messenger RNA in the outer laminae of the lumbar spinal cord when challenged 4 h later with a 50 microliters intraplantar injection of 5% formalin. Animals pretreated with saline or sense oligodeoxynucleotide showed marked increases in Fos protein (2 h after formalin challenge) and preprodynorphin mRNA (20 h after formalin challenge) in the lumbar region of the cord ipsilateral to the side of the injection. The behavioural consequences of antisense pretreatment were an increase in the formalin-induced licking/biting responses during the tonic, but not the acute phase. These observations could be interpreted as representing a sequence of events beginning with the formalin-induced increase in the transcription factor Fos, which in turn increases the synthesis of preprodynorphin messenger RNA resulting in the production of the dynorphin opioid peptides which then exert a modulatory antinociceptive action. PMID- 7777162 TI - Interaction of convergent pathways that inhibit N-type calcium currents in sensory neurons. AB - Norepinephrine and GABA inhibit omega-conotoxin GVIA-sensitive (N-type) calcium current in embryonic sensory neurons by separate pathways. We have investigated the mechanisms that limit the modulation of N current by varying the level of activation for a single pathway or simultaneously activating multiple pathways. Calcium currents were measured with tight-seal, whole-cell recording methods. Simultaneous application of the two transmitters at saturating concentrations produced a larger inhibition of the current than either transmitter by itself, but the maximal inhibition was not linearly additive. Maximal, direct activation of GTP-binding proteins by intracellular application of guanosine 5'-(3-O-thio) triphosphate (GTP gamma S) resulted in a similar limit to the inhibition; furthermore, GTP gamma S did not enhance the maximal inhibition produced by co application of transmitters. Interventions downstream in the modulatory pathway (e.g. direct activation of protein kinase C or inhibition of protein phosphatases) were also unable to alter the maximal limit for inhibition. These results suggest that transmitter-mediated inhibition is not limited by receptor number, levels of G-protein or protein kinase C activation, or degree of phosphorylation; rather, the extent of inhibition may be limited by the structural properties of the N channels themselves. PMID- 7777164 TI - Protective effect of basic fibroblast growth factor-heparin and neurotoxic effect of platelet factor 4 on ischemic neuronal loss and learning disability in gerbils. AB - Platelet factor 4, which has a potent affinity for heparin, has been shown to inhibit the binding of basic fibroblast growth factor to the cell surface receptor and to counteract the biological activities of basic fibroblast growth factor in certain peripheral tissues. In the present in vitro [125I]basic fibroblast growth factor binding experiments, platelet factor 4 consistently inhibited the binding of iodinated basic fibroblast growth factor to cell membranes of the gerbil hippocampus. To investigate the in vivo function of endogenous basic fibroblast growth factor and/or basic fibroblast growth factor receptor possibly activated in the ischemic gerbil brain, we infused platelet factor 4 continuously into the left lateral ventricle with an osmotic minipump. When platelet factor 4 infusion was started within three days after a 3-min ischemic insult, it significantly enhanced ischemia-induced learning disability and ischemic neuronal loss in the CA1 region of the hippocampus, as demonstrated by the results of the step-down passive avoidance task and by subsequent histological examinations. Infusion of platelet factor 4 into the cerebral ventricle of intact gerbils did not affect learning ability or CA1 neuron number. Basic fibroblast growth factor-neutralizing antibody, when infused continuously in the cerebral ventricle, also exhibited a neurotoxic effect in ischemic but not intact gerbils. Basic fibroblast growth factor co-infused with heparin, but not basic fibroblast growth factor alone, rescued a significant number of ischemic neurons which were destined to degenerate without the infusion of heparinized basic fibroblast growth factor, and it prevented ischemia-induced learning disability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777165 TI - Peripheral lipopolysaccharide stimulation induces interleukin-1 beta messenger RNA in rat brain microglial cells. AB - The inflammatory cytokine interleukin-1 acts as an endogenous pyrogen in organisms affected by infectious diseases and has been shown to influence the activity of the central nervous system. Using in situ hybridization histochemistry, we have examined the cellular source of interleukin-1 beta in rat brain after peripheral stimulation with the bacterial lipopolysaccharide, a potent inducer of interleukin-1. Whereas no interleukin-1 beta messenger RNA could be detected in brains in unstimulated rats, lipopolysaccharide induced a transient, high and widespread expression of interleukin-1 beta messenger RNA in the entire brain. The highest levels of interleukin-1 beta messenger RNA were observed 6-8 h after stimulation with lipopolysaccharide. Using a combination of non-radioactive in situ hybridization and immunocytochemistry with the microglial specific antibody OX-42, interleukin-1 beta messenger RNA-positive cells could be identified as microglia. We conclude that brain microglial cells are the major source of interleukin-1 beta messenger RNA after peripheral administration of lipopolysaccharide. PMID- 7777167 TI - Previous stress alters corticotropin-releasing factor neurotransmission in the locus coeruleus. AB - Spontaneous and stress-evoked discharge of locus coeruleus neurons were characterized in rats with a history of stress. Rats exposed to one or five daily 30-min sessions of footshock were anesthetized with halothane and surgically prepared for locus coeruleus single-unit recording immediately following the last session. Locus coeruleus spontaneous discharge rate and discharge evoked by sciatic nerve stimulation were comparable between acutely and repeatedly stressed rats and controls. In contrast, locus coeruleus activation produced by intracerebroventricular administration of corticotropin-releasing factor (3 micrograms) or by hypotensive challenge (which requires endogenous corticotropin releasing factor release in the locus coeruleus) was greatly attenuated in acutely stressed rats. The corticotropin-releasing factor dose-response curve was shifted to the right in acutely stressed rats compared with controls. In repeatedly stressed rats, the effects of 3 micrograms corticotropin-releasing factor on locus coeruleus discharge were similarly diminished. Although the maximum effect produced by corticotropin-releasing factor was decreased in these rats, the dose-response curve was shifted to the left, indicative of sensitization. Hypotensive challenge, which was ineffective in acutely stressed rats, increased locus coeruleus discharge of repeatedly stressed rats by a similar magnitude as in matched controls. The return of locus coeruleus responsiveness to hypotension in repeatedly stressed rats may be related to the sensitization to corticotropin-releasing factor. Finally, the protocol of repeated stress did not alter the affinity or density of corticotropin-releasing factor receptors in either the frontal cortex or brainstem. Taken together, the results suggest that a history of stress alters corticotropin-releasing factor neurotransmission in the locus coeruleus at the postsynaptic level. However, these effects are not reflected by corticotropin-releasing factor binding kinetics in brainstem. Stress-induced changes in corticotropin-releasing factor neurotransmitter function in the locus coeruleus may play a role in certain symptoms of stress-related psychiatric disorders. PMID- 7777166 TI - Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. AB - We have investigated the mechanism of nitric oxide-induced damage in glial cells. Genomic DNA isolated from astrocytes and microglia, treated for 18 h with varying concentrations of a nitric oxide donor, was analysed by electrophoresis. No DNA damage was evident. Oligodendrocytes, treated with 2 mM nitric oxide for 3-48 h, showed single stranded breaks at 48 h but no laddering of nucleosomic fragments of DNA. When analysed by electron microscopy, ultrastructural changes in oligodendrocytes treated with 1 mM nitric oxide for 24 h showed intact nuclei but alterations in membranes and organelles characteristic of necrosis, including disrupted mitochondria with dissolution of their christae. Astrocytes, a glial cell type that we have previously shown to be much less sensitive to nitric oxide induced damage, did not show ultrastructural changes. DNA analysis by flow cytometry of glial cells treated with nitric oxide supported the apparent necrotic-type death in oligodendrocytes. Double staining of oligodendrocytes, using Hoechst 33342 and propidium iodide for the simultaneous assessment of both apoptotic and necrotic cells, demonstrated that, while the proportion of dead cells increased with time and increasing concentrations of nitric oxide, the death was due to necrosis and not apoptosis. In this study, we demonstrate that direct exposure to soluble nitric oxide, produced in vitro from a nitric oxide donor chemical, ultimately kills oligodendrocytes by necrosis. Microglia and astrocytes maintain DNA and organelle integrity when exposed to exogenous nitric oxide. PMID- 7777168 TI - Patterns of expression of SSTR1 and SSTR2 somatostatin receptor subtypes in the hypothalamus of the adult rat: relationship to neuroendocrine function. AB - The neuropeptide somatostatin is the major physiological inhibitor of growth hormone secretion. With the aim of identifying the receptor subtypes through which this neuropeptide may be exerting its neuroendocrine actions in the brain, we have examined by in situ hybridization the distribution of the messenger RNA for SSTR1 and SSTR2 isoforms in the hypothalamus of adult male and female rats. Both receptor subtypes were highly expressed in the medial preoptic area, suprachiasmatic nucleus and arcuate nucleus. High SSTR1, but low SSTR2, expression was evident in the para- and periventricular nuclei as well as in the ventral premammillary nucleus. Conversely, moderate to high SSTR2, but low SSTR1, messenger RNA levels were detected in the anterior hypothalamic nucleus, ventromedial and dorsomedial nuclei and medial tuberal nucleus. Taken together, these distributional patterns conform to those of somatostatin binding sites as visualized by in vitro autoradiography, suggesting that an important proportion of SSTR1 and SSTR2 receptors in the hypothalamus are associated with the perikarya and dendrites of intrinsic neurons. The distribution of SSTR1 expressing cells within the periventricular, paraventricular and suprachiasmatic nuclei was similar to that of neurons previously reported to contain and/or express somatostatin in the brain suggesting that some of the SSTR1 receptors may correspond to autoreceptors. Within the arcuate nucleus, the distribution of SSTR1 and SSTR2 messenger RNA-expressing cells was comparable to that of neurons previously found to selectively bind somatostatin-14 within this area. Given that over one third of these cells also contain and express growth hormone-releasing factor, the present findings suggest that both of these receptor subtypes are involved in the central regulation of growth hormone-releasing factor secretion by somatostatin. Taken together, the present results suggest that SSTR1 and SSTR2 somatostatin receptor messenger RNAs are heavily expressed in those neurons containing somatostatin and/or growth hormone-releasing factor and thereby imply a role for both SSTR1 and SSTR2 somatostatin receptor subtypes in neuroendocrine regulation of growth hormone secretion in both sexes of this species. PMID- 7777169 TI - The AMPA glutamate receptor GluR3 is enriched in oxytocinergic magnocellular neurons and is localized at synapses. AB - The cellular localization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor, GluR3, was identified using antibodies that recognize the N-terminus of the predicted polypeptide sequence of GluR3. Regional immunoblot analysis of monkey brain homogenates identified a protein of approximately 102,000 mol. wt that was enriched in hypothalamus. Immunocytochemistry demonstrated that GluR3 was enriched within the hypothalamic magnocellular neurosecretory nuclei and axons of the hypothalamo-neurohypophysial tract in rat and monkey. GluR3 immunoreactivity co-localized to oxytocin containing, but not vasopressin-containing, neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus and accessory magnocellular nuclei. Ultrastructurally, GluR3 immunoreactivity was enriched throughout cytoplasm of the somatodendritic compartment and was associated with postsynaptic and presynaptic structures. GluR3 immunoreactivity was frequently observed to be clustered at the plasma membrane of the somatodendritic compartment, consistent with the predicted localization of a membrane-bound ion channel. Additionally, GluR3-immunoreactive axon terminals in synaptic contact with unlabeled dendrites within the retrochiasmatic area and bed nucleus of the stria terminalis were observed, providing morphological evidence for a presynaptic alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionate receptor. By immunoblot analysis and immunocytochemistry using antibodies directed against a specific alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionate receptor in rat and monkey brain, our findings suggest a highly selective hypothalamic distribution of the GluR3 subunit that may have functional significance in the glutamatergic regulation of oxytocinergic neurons. PMID- 7777170 TI - Nasal and temporal retinal ganglion cells projecting to the midbrain: implications for "blindsight". AB - We placed pellets of horseradish peroxidase in the superior colliculus of four macaque monkeys and retrogradely labelled the retinal ganglion cells of both eyes. The ratio of labelled cells in the contralateral nasal retina and the ipsilateral temporal retina was no different from the ratio found after implants in the optic nerve, which label the entire afferent pathway. Our finding therefore invalidates the proposal that prominent differences in the properties of "blindsight" in monocular nasal and temporal visual fields arise from differences in the projection from the nasal and temporal retina to the midbrain. We also measured the size of the soma and dendritic field of the labelled ganglion cells (mostly gamma cells) and compared them with those of alpha and beta cells that project to the dorsal lateral geniculate nucleus. Soma size was very close to that of beta cells at all eccentricities but was much smaller than that of alpha cells. Dendritic field size was significantly larger than that of beta cells but was smaller than that of alpha cells. The number of primary dendrites was counted for cells labelled from the midbrain and in samples of alpha and beta cells labelled from the optic nerve. At eccentricities of 3-7 mm there was a consistent and prominent difference between beta and gamma cells. The results show that at intermediate eccentricities even ganglion cells whose distal dendrites are too poorly labelled to reveal their morphological class can never the less be categorized as alpha, beta or gamma by using a combination of soma size and number of primary dendrites. This is particularly useful when attempting to classify retinal ganglion cells following microinjections into selected target nuclei of optic axons. PMID- 7777171 TI - Behavioural and cellular responses to light of the circadian system of tau mutant and wild-type Syrian hamsters. AB - The tau mutation shortens the free-running circadian period of the activity rhythm of the Syrian hamster from around 24 h in the wild-type, to 20 h in the homozygous mutant. The aim of this study was to examine the effects of light pulses on the activity rhythms and expression of c-fos in the suprachiasmatic nuclei of wild-type and mutant hamsters. This would make it possible to determine the relative durations of subjective day and night, and thereby characterize further the effect of the mutation upon the circadian cycle. Presentation of light pulses (15 min) to animals kept in dim red light for seven to 10 days induced phase-dependent shifts in the onset of activity. During subjective day (inactive phase) there was no effect of light upon the activity rhythm of either normal or mutant animals. Early in subjective night (i.e. after the start of the active phase), light pulses induced phase delays of approximately one circadian hour in both phenotypes. However, later in subjective night light pulses induced phase advances in activity rhythms. The magnitude of the advance phase shifts differed considerably between the two phenotypes, with the wild-types typically showing shifts of about one circadian hour, while the mutants showed much larger advances of up to 12 circadian hours. In both strains, advances were observed following light at circadian time 22 but not after light at circadian time 24. The relative duration of subjective night was therefore comparable in the mutants and wild-types i.e. around 11 circadian hours. In order to examine the light induced expression of the immediate early gene c-fos at different circadian phases, animals received a second light pulse (15 min) or a control "dark pulse" at the same circadian time as they had received the first, but seven to 10 circadian days later. They were perfused 1 h after the start of the pulse and brains processed for the immunocytochemical detection of Fos, the protein product of c-fos. Animals receiving dark pulses showed minimal Fos immunoreactivity in the suprachiasmatic nucleus, regardless of the circadian time of presentation of the stimulus. During subjective day (circadian times 4-11), light induced very little Fos immunoreactivity. In contrast, light presented during subjective night (after circadian time 12) induced a dense pattern of Fos immunoreactivity in the ventrolateral, retino-recipient region of the suprachiasmatic nucleus of both wild-type and mutant animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777172 TI - Neuronal localization of pituitary adenylate cyclase-activating polypeptide 38 in the adrenal medulla and growth-inhibitory effect on chromaffin cells. AB - The chromaffin cells of the adult rat adrenal medulla are essentially growth arrested in situ, but can proliferate in vitro, suggesting the existence of growth inhibitory factors in the adrenal gland. We have investigated whether pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) could be involved in the growth arrest of adrenal chromaffin cells. In adult rat adrenal gland, PACAP38 was detected by radioimmunoassay and high-performance liquid chromatography and its concentration in the medulla was estimated as 24 nmol/kg wet tissue. Immunohistochemistry of the neonatal and adult rat adrenal medulla showed PACAP38 immunoreactivity in a widely distributed network of delicate nerve fibers surrounding the chromaffin cells. In a primary culture system, PACAP38 inhibited growth factor-stimulated DNA synthesis by 90% in neonatal and adult rat chromaffin cells with half-maximal inhibition at 4 and 0.5 nM, respectively, as demonstrated by bromodeoxyuridine pulse-labeling and immunocytochemical staining of cell nuclei. In comparison, corticosterone inhibited neonatal and adult chromaffin cell proliferation by 70% and 95%, respectively, with half-maximal effect at 100 nM. In neonatal chromaffin cells, 100 nM PACAP38 and 1 microM corticosterone added together abolished proliferation completely (99.8% inhibition). Finally, PACAP38 increased cell survival but showed little neurite promoting activity in the chromaffin cells. Our data suggest that neurally derived PACAP38, in conjunction with glucocorticoids, may override growth factor mitogenic signals, leading to the postmitotic state of chromaffin cells in the adult adrenal medulla. PMID- 7777174 TI - Unilateral grafting of fetal neocortex into a cortical cavity improves healing of a symmetric lesion in the contralateral cortex of adult rats. AB - Fetal neocortical tissue (ED 14) was grafted unilaterally into a cortical cavity made bilaterally in the sensorimotor cortex of adult rats. Transplantation was done immediately after the lesion (group TR0, n = 8) or with 14-day delay (group TR14, n = 8). Six rats served as lesion only controls (group LES). After long term survival (up to 15 months) the brains were photographed and surface areas of transplant and contralateral cavities were measured by means of a graphic tablet. The results show that (a) the presence of a transplant in one lesion cavity in the cortex decrease the size of a similar cavity in the contralateral cortex and that (b) the better host transplant integration there is, the greater the effect on the contralateral lesion. No correlation between the size of the transplant and the size of the symmetric traumatic lesion was found. The ameliorating effect of the transplant on the contralateral cortical lesion size is most likely related the long-term influence of growth of trophic factors released by transplanted cells which lead to the healing of the symmetric lesion. PMID- 7777175 TI - Cortical potentials during gap and non-gap paradigms using manual responses in humans. AB - An experiment was conducted on naive human subjects to measure the time benefits on finger reaction times produced by the offset of a central fixation point 200 ms before the appearance of a target stimulus in the periphery. Subjects produced a shift advancement of manual reaction times. Simultaneously, the event-related potentials were recorded. The gap paradigm induced offset visual evoked potentials and a frontal negativity, it also induced a higher P300 than the non gap condition. The results suggest that the gap promotes the speeding of the response by a cortical priming. PMID- 7777173 TI - Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. AB - The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function. PMID- 7777176 TI - Spinal distribution and brainstem projection of lamina I neurons in the pigeon. AB - Lamina I neurons of the spinal dorsal horn serve nociception both in mammals and in birds. The projection of these neurons to the brain is largely unknown in birds. Injections of retrogradely transported fluorescent tracers into various brainstem nuclei showed that these neurons, which are distributed throughout the spinal cord, heavily project to the nucleus of the solitary tract and the parabrachial area but not to the hypothalamus. Injections into the nucleus of the solitary tract revealed a group of neurons located in Lissauer's tract of thoracic segments. These results point to a functional role of spinal lamina I neurons in avian visceronociception. PMID- 7777177 TI - Two conformational states of amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. AB - Since the discovery of soluble amyloid-beta (sA beta), it became clear that the same amino acid sequence can have both a fibrillar or a soluble state. In this work, we describe the isolation of two different species derived from synthetic A beta(1-40) differing in their conformational and fibrillogenesis properties. The separation was performed taking advantage of the fact that only one species is sedimentable by centrifugation after 2 weeks of incubation at 1 mg/ml. One species is highly amyloidogenic (A beta ac) and has an antiparallel beta-sheet structure and the other one is poorly amyloidogenic (A beta nac) and contains mainly random coil or alpha-helix structure. Chemical changes were not detected in the primary structure of both species and the differences in the physical properties and very likely in biological behaviour are thought to have a conformational basis. We propose that the transformation of the non-amyloidogenic into the amyloidogenic conformation could be the fundamental event in the pathological polymerization of sA beta and in the development of Alzheimer's disease. PMID- 7777179 TI - Increased immunostaining for L-ornithine decarboxylase occurs in neocortical neurons of Alzheimer's disease patients. AB - We investigated the distribution of L-ornithine decarboxylase (ODC), an enzyme known to be involved in several developmental and restorative processes, in neocortical brain areas of Alzheimer's disease (AD) and normal patients by means of immunohistochemistry. While ODC immunoreactive material was only scarcely distributed in neocortical neurons of control brains, neocortical specimens from AD brains stood out by intense immunostaining for ODC. Dendrites and, to a lesser extent, axons of neurons from AD brains showed a strong immunoreaction to the enzyme, whereas neurons from non-affected brains displayed only a weak circumnuclear reaction pattern. Our results support the idea that neurorestorative processes take place in AD brains and that the ODC/polyamine system might be actively involved in this process. PMID- 7777178 TI - Pharmacological differentiation of the effects of co-activation of beta adrenergic and metabotropic glutamate receptors in rat hippocampus. AB - Activation of metabotropic glutamate receptors (mGluRs) can potentiate the cAMP response elicited by activation of beta-adrenergic receptors (beta ARs) in the hippocampus. We have shown that co-activation of mGluRs and beta ARs induces both an acute depression of excitatory synaptic transmission and a long-lasting excitation of CA1 pyramidal cells. However, these studies were performed using a non-selective mGluR agonist. We have now used subtype selective mGluR agonists, and report that while the acute depression of transmission exhibits a pharmacology consistent with mediation by this mGluR subtype, the lasting excitation of CA1 pyramidal cells may be mediated by an interaction between beta ARs and mGluRs that are coupled to phosphoinositide hydrolysis. PMID- 7777180 TI - Postcentral neurons of alert monkeys activated by the contact of the hand with objects other than the monkey's own body. AB - In the caudal postcentral finger region near or in the anterior bank of the intraparietal sulcus of alert monkeys, we found neurons that were activated selectively by the contact of the hand to certain common objects such as bottle brushes, acrylic plates, parts of the stabilized monkey's chair, etc. All of these neurons were not activated when the monkey's hand was contacted with the monkey's own body. We concluded that these neurons are concerned with the haptic discrimination of common objects with the selectivity to one of various material variables of objects, and that the process involves differentiation of the object from the animal's own body. PMID- 7777181 TI - Kappa opioid receptor agonists suppress absence seizures in WAG/Rij rats. AB - Involvement of the kappa opioid receptor in the regulation of epileptic activity was studied in WAG/Rij rats, a genetic model of absence epilepsy. I.c.v. administration of the kappa agonists U50,488H (trans-3,4-dichloro-N-methyl-N-[2 (1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), U69,593 (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl)benzeneacetamide) or PD117,302 ((+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzo[b]thiophene-4-acetamide), 50 and 150 micrograms/5 microliter each, dose-dependently decreased the number and mean duration of spike wave discharges (SWD). Peripheral administration of U50,488H (10 and 30 mg/kg s.c.) also attenuated the seizure activity in this model. The specific kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 micrograms/5 microliters i.c.v., 18 h before EEG registration) moderately increased the number of SWD, which suggests that endogenous opioids acting through kappa receptors may tonically inhibit the seizure activity in these rats. In addition, the enhancement of an absence-like seizure activity induced by the specific mu opioid receptor agonist D-Ala2-N-methyl-Phe4-Gly5-ol-enkephalin (DAMGO, 0.7 microgram/5 microliters i.c.v.) was also attenuated in rats pretreated with U50,488H, U69,593 or PD117,302. These data indicate that activation of the kappa opioid receptor exerts an inhibitory effect on absence-like seizure activity in WAG/Rij rats. PMID- 7777182 TI - Female rats are more susceptible to the development of neuropathic pain using the partial sciatic nerve ligation (PSNL) model. AB - A comparison study was conducted to determine if a gender difference could be detected using an animal model for causalgia. The sciatic nerve was tightly ligated so that 1/3 to 1/2 of the nerve thickness was trapped by the ligature, just distal to the point at which the posterior biceps semitendinosus nerve branches off the common sciatic nerve. By measuring paw withdrawal from innocuous stimulation with Von Frey filaments, the percent of rats displaying average mechanical sensitivity of the injured paw that was significantly elevated compared to sham or unoperated control animals (days 22-24) was 28.6% for the male group versus 63.6% for the female group. Our animals did not display a consistent response in withdrawal latency to heat applied to the plantar surface of the root (hyperpathia). The data suggests that female rats are significantly more susceptible to developing neuropathic pain than male rats using this experimental model for causalgia. PMID- 7777183 TI - Intracellular acidification is not a prerequisite for glutamate-triggered death of cultured hippocampal neurons. AB - Glutamate decreased intracellular pH (pHi) in cultured rat hippocampal neurons. The protonophore, FCCP (1 microM), produced an acidification comparable to that produced by glutamate. Application of glutamate to FCCP-treated cells, returned pHi to resting levels. This alkaline shift resulted from a glutamate-induced membrane depolarization that removed the driving force across the plasmalemma for H+ entry via FCCP. The endogenous protonophore, arachidonic acid (10 microM), produced pHi changes similar to those elicited by FCCP. Because application of glutamate and FCCP in combination did not change pHi, this treatment was used to determine the role of glutamate-induced acidification in neurotoxicity. FCCP (1 microM, 5 min) did not affect neuronal viability, either alone or in combination with various concentrations of glutamate, as indicated by the release of lactate dehydrogenase into the bathing medium. Thus, acidification was not the cause of glutamate-induced cell death although, it may be symptomatic of neurotoxic processes. PMID- 7777184 TI - Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors. AB - We compared some binding parameters of [3H]nemonapride and [3H]spiperone in human dopamine D4 (hD4) receptors with three different numbers of tandem repeat units. Although both of the radioligands showed similar affinity constants for each hD4 receptor variant, the maximal number of binding sites labeled by [3H]nemonapride was approximately 1.35-fold higher than that by [3H]-spiperone for all variants. Estimated Ki values for the inhibition of [3H]nemonapride binding by a series of dopaminergic ligands were highly correlated to respective values obtained for the inhibition of [3H]spiperone binding to each hD4 receptor. These results suggest that the hD4 receptor, as shown for the D2 receptor, may exist in multiple molecular forms as a monomer-dimer equilibria, and that [3H]spiperone may discriminate in the multiple molecular forms. PMID- 7777186 TI - Temporal pattern of internucleosomal DNA fragmentation in the striatum and hippocampus after transient forebrain ischemia. AB - Transient forebrain ischemia in rodents caused internucleosomal DNA fragmentation that appeared in the striatum 24 h after reperfusion, and in the hippocampus 72 h after reperfusion. Gel electrophoresis and an in situ technique to label 3' termini of endonuclease generated DNA fragments demonstrated similar temporal patterns. These data show that endonuclease activation accompanies the demise of selectively vulnerable neurons following transient forebrain ischemia. PMID- 7777185 TI - Enhanced glutamatergic neurotransmission facilitates classical conditioning in the freely moving rat. AB - Centrally active drugs that enhance alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-gated currents by increasing the amplitude and duration of fast, excitatory synaptic responses in the hippocampus have recently been described. The effects of the compound 1-(1,3-benzodioxol-5-ylcarbonyl) perperidine (BDP) on associative and non-associative aspects of the classically conditioned eyeblink response in the freely moving rat were examined. Rats injected with BDP blinked significantly more to an acoustic stimulus of 85 dB than did vehicle controls, indicating that the drug enhances alpha responding to discrete auditory cues. Using a less intense stimulus of 80 dB, rats injected with BDP did not exhibit alpha responding or pseudo-conditioning, yet learned the conditioned response at a facilitated rate. These results suggest that increasing excitatory neurotransmission enhances the processing of sensory information and may contribute to subsequent contingency detection. PMID- 7777187 TI - Chronically administered 3-nitropropionic acid induces striatal lesions attributed to dysfunction of the blood-brain barrier. AB - 3-Nitropropionic acid (3-NPA), an irreversible inhibitor of succinate dehydrogenase, was administered to rats and the characteristics of the neuronal damage were investigated. Injections of 3-NPA (15 mg/kg s.c.) every 2 or 3 days for 1-2 weeks induced a mild neuronal loss and neutrophil invasions in the striatum (STR). The same administration for 4 weeks induced specific symmetric lesions in the lateral STR although the size was variable in each animal. Inside the lesions, strong neutrophil invasions and a strong immunoreaction for IgG, C3 as well as complement factor C3b/C4b receptor (C3b/C4br) were detected. Lesioned sites lost the immunoreaction for GFAP while the marginal areas contained abundant GFAP-labeled astrocytes around the vessels. In intoxicated animals, there was a weak but stout immunoreaction for IgG and C3b/C4br localizing around vessels in the STR even when there were no lesions or neuronal loss. The data suggest that the blood-brain barrier dysfunction is responsible for the specific vulnerability of the STR for the toxin. PMID- 7777188 TI - The effect of post-ischemic hypothermia following repetitive cerebral ischemia in gerbils. AB - Repetitive ischemia may result in more severe damage than a single similar duration insult. Inter-ischemic hypothermia significantly decreases this damage. It is unclear if protection would be evident if cooling was delayed until after the repeated insults. In this study, we evaluated the effects of 3 h of mild cooling (34-35 degrees C) beginning immediately after the third insult of ischemia, 0.5 h after the third insult and 1 h after the third insult in a gerbil model of repetitive ischemia. Neuronal damage was assessed in the cerebral cortex (CTX), hippocampus (CA1, CA4), striatum (STR), thalamus (THL), medial geniculate nucleus (MGN), and the substantia nigra reticulata (SNr). A '4-point' damage scale was used and evaluation was done in a blinded way. Group comparisons were done using the Mann-Whitney U-test for significance between the control and hypothermic groups. Immediate hypothermia after the third ischemic insult produced a significant protection in the CTX (P < 0.05), hippocampus (CA1 and CA4, P < 0.01), STR (P < 0.001), SNr (P < 0.01), MGN (P < 0.01) and THL (P < 0.01). Cooling at 0.5 and 1 h after the third insult produced no protection when compared to ischemic controls. The window of opportunity with hypothermia is narrow in repetitive ischemia. To be effective, therapy must be initiated as soon as possible after ischemic insults. PMID- 7777189 TI - Expression of glutamate (AMPA type) and gamma-aminobutyric acid (GABA)A receptors in the rat caudal trigeminal spinal nucleus. AB - The localization of GABAA receptor gamma 1 and gamma 2 subunits and the AMPA-type glutamate receptor subunits GluR1 and GluR2/3 were identified in the caudal trigeminal spinal tract nucleus (TNC) by immunohistochemistry using specific antibodies. The receptor species on the projecting neurons to the thalamus in TNC were also examined. A retrograde tracer, Fluoro-gold (FG), was injected into the thalamus, and the sections were simultaneously labeled with the antibodies. Injection of FG into the ventral posteromedial nucleus of the thalamus resulted in labeling of scattered neurons contralaterally in the TNC. Most of the neurons labeled by retrograde tracing also showed gamma 1- and gamma 2-like immunoreactivity, while many of the neurons containing FG lacked GluR1- and GluR2/3-like immunoreactivity. These findings show that neurons projecting to the thalamus from the TNC receive GABAergic input via GABAA receptors containing gamma 1 and gamma 2 subunits, while many neurons expressing the AMPA-type receptor did not project to the thalamus. PMID- 7777190 TI - Presence of specific platelet-activating factor binding-sites in neuroblastoma N1E-115 cells. AB - In this study we reported evidence for the existence of specific binding sites for platelet-activating factor (PAF) in neuroblastoma N1E-115 cells. The specific [3H]PAF binding reached a steady state level within 60 min at 25 degrees C. Scatchard analysis of the specific [3H]PAF binding revealed the presence of two apparent populations of binding sites. The high-affinity binding site possessed a Kd1 of 2.5 +/- 0.6 pM and Bmax1 = 57.3 +/- 20.0 fmol/mg protein. The low-affinity binding site possessed a Kd2 = 3.2 +/- 1.0 nM and Bmax2 = 4.4 +/- 2.1 pmol/mg protein. Furthermore, the total [3H]PAF binding was partially displaced by unlabelled PAF, PAF antagonists BN 52021 and BN 50730 in a dose-dependent manner. This study confirms the presence of specific PAF receptors in neuronal cells. PMID- 7777191 TI - Antioxidant lazaroids enhance differentiation of C2 skeletal muscle cells. AB - We have examined the incidence of new antioxidant compounds, so-called lazaroids, on the morphological and biochemical aspects of differentiation of C2 mouse skeletal muscle cells. We show that three lazaroids (U-74006F, U-74389F and U 83836E) enhance fusion of myogenic cells when added at the day of fusion. A parallel increase in nicotinic acetylcholine receptor expression and skeletal muscle alpha-actin content was observed. This promoting effect of lazaroids on myogenesis could be related to inhibition of free radical-mediated muscle damage. Therefore, one could expect that lazaroids might be useful in the treatment of degenerating muscle diseases such as Duchenne muscular dystrophy. PMID- 7777192 TI - Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau. AB - Clinical diagnosis for Alzheimer's disease (AD) is provided by the criteria of DSMIV and clinical progress in addition to imaging analysis with MRI after negative screening. The final exclusive diagnosis is confirmed by the neuropathological findings of neurofibrillary tangles and senile plaques in autopsy brains. We developed a new ELISA system to measure the amount of tau in cerebrospinal fluids (CSF) using phosphorylation-independent and sequence specific antibodies. The present ELISA was sensitive enough to detect tau in CSF of normal subjects. The amount of tau was significantly elevated in CSF of AD subjects compared with those of normal subjects and subjects with dementia of cerebrovascular disease, suggesting that tau in CSF reflects the massive and continuous neuronal cell death in the AD brain. In conclusion, we established an ELISA system which enabled us to detect tau in CSF and demonstrated that tau was significantly and specifically elevated in CSF of AD subjects. This assay system can provide us with a potent diagnostic tool for clinical AD. PMID- 7777193 TI - Increased cerebrospinal fluid tau in patients with Alzheimer's disease. AB - One of the pathological features in Alzheimer's disease (AD) is neurofibrillary tangles in the brain. The main constituent of tangles is the microtubuli associated protein tau in a hyperphosphorylated state. Tau is also released into cerebrospinal fluid (CSF), and in this study we have used an enzyme linked immunosorbent assay to measure tau in CSF from AD and control cases. Our findings show that tau levels in AD cases are significantly elevated compared to healthy control individuals. We suggest that tau may serve as a biochemical marker of Alzheimer's disease. PMID- 7777195 TI - Neuronal pathways mediating head turning behavior in Aplysia. AB - Seaweed applied to the head of Aplysia elicits a head turning response in the direction of the stimulus. The major motor neurons involved in head turning appear to be located largely in the pedal ganglion. Using an autoradiographic technique, we obtained evidence that there are afferents in the skin of the head that project directly to the pedal ganglion by way of the cerebral-pleural connectives. Bilateral lesioning of the cerebral-pleural connectives, however, did not interfere with head turning, and unilateral lesions of either a cerebral pedal or cerebral-pleural connective did not differentially affect turns evoked by stimuli applied ipsilaterally or contralaterally to the lesion. However, a combined unilateral lesion of a cerebral-pedal and cerebral-pleural connective resulted in elimination or significant reduction of ipsilateral turns. The data suggest that head turns elicited by food, are mediated by the combined information travelling in both the pedal and pleural connectives. PMID- 7777194 TI - Neuroprotective effect of phenytoin against in utero hypoxic brain injury in fetal guinea pigs. AB - The present study tests the hypothesis that phenytoin, an antiepileptic agent known to block Na+ and Ca2+ channels, will prevent hypoxic brain injury in the fetus by preventing lipid peroxidation and preserving Na+,K(+)-ATPase activity. Studies were performed in 37 fetuses obtained from pregnant guinea pigs at 58-60 days gestation (term). The pregnant guinea pigs were divided into four groups: a normoxic group, a hypoxic group, a normoxic group treated with phenytoin, and a phenytoin treated hypoxic group. There were eight to ten fetal guinea pigs in each group. The treatment groups were given phenytoin 30 mg/kg (50 mg phenytoin/ml solvent) intraperitoneally. Hypoxia was induced by exposing the guinea pigs to 7% oxygen for 60 min. This level of hypoxia has been shown to decrease ATP and phosphocreatine levels by 90%. The fetal brains were harvested and the brain cell membranes were prepared from each group of fetuses. Na+,K(+) ATPase activity and lipid peroxidation products, measured as relative fluorescent intensity, were determined. The mean Na+,K(+)-ATPase activity in the control, hypoxic, phenytoin-normoxic and phenytoin-hypoxic groups was 56.4 +/- 9.7, 37.9 +/- 10.6, 47.0 +/- 8.4 and 52.0 +/- 9.7 mumol inorganic phosphate/mg protein per h, respectively. The hypoxic group had significantly less Na+,K(+)-ATPase activity than both the normoxic group (P < 0.01), and the phenytoin treated hypoxic group (P < 0.05). There was no significant difference between the normoxic group and either of the phenytoin-treated groups (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777196 TI - Norepinephrine and epinephrine levels in the brain of alloxan diabetic rats. AB - Thirty days after induction of experimental diabetes the brain catecholamines namely, norepinephrine (NE) and epinephrine (E) were studied in discrete brain regions (striatum, hippocampus, hypothalamus, midbrain, pons and medulla, cerebellum and cerebral cortex) in control, alloxan-diabetic untreated and insulin-treated diabetic rats. E showed significant increase in striatum, hippocampus and hypothalamus, whereas NE was increased in hypothalamus, and decreased in pons and medulla significantly in untreated diabetic rats. These effects were not seen in the insulin-treated diabetic rats. PMID- 7777197 TI - Acceleration of GABA-dependent desensitization by mutating threonine 266 to alanine of the alpha 6 subunit of rat GABAA receptors. AB - Various GABAA receptor subunits share four highly homologous putative transmembrane domains (M1 to M4) and have been proposed to form an ion channel of pentameric structure with M2 lining the pore. The carboxyl terminal side of M2 contains three amino acid residues containing a hydroxyl group, which are Thr 265, 266 and serine 268 in the alpha 6 subunit. In order to study their functional role, we generated mutants of the alpha 6 subunit carrying a single point mutation of threonine 265 or 266 to alanine, or serine 268 to glycine. Co expression of the mutants with beta 2 and gamma 2 subunits in human embryonic kidney cells produced functional receptors which are similar to the wild type in their sensitivity to a benzodiazepine agonist (U-92330), insensitivity to Zn, anion permeability, and GABA dose-response profiles as monitored with the whole cell patch clamp technique. Only in the alpha 6T266A beta 2 gamma 2 subtype, however, GABA-induced Cl- currents decayed much more rapidly than the wild type (about 10 times faster). Analysis of the GABA dependency of desensitization indicates that the T266A mutation enhanced the desensitization rate with little effect on the recovery rate from desensitization or on the half-maximal GABA concentration. We conclude that threonine 266 in the alpha 6 subunit plays a pivotal role in desensitization processes of GABAA receptors. PMID- 7777199 TI - Protective effects of probucol against glutamate-induced cytotoxicity in neuronal cell line PC12. AB - The sympathetic nerve cell line PC12 is reportedly destroyed by glutamate in a concentration-dependent manner. In this study, cytotoxicity induced by 10 mM glutamate was blocked in a dose-dependent manner by incubating or pre-incubating cells with the antioxidant probucol (1-50 microM). Probucol also inhibited the increase in cellular thiobarbituric acid-reacting substances induced by glutamate exposure. These results suggest that the propagation of cellular lipid peroxidation may be related to glutamate-induced toxicity in PC12 cells. PMID- 7777198 TI - Expression and complex formation of soluble N-ethyl-maleimide-sensitive factor attachment protein (SNAP) receptors in clonal rat endocrine cells. AB - Syntaxin, synaptosome-associated protein 25 (SNAP-25) and synaptobrevin are neuronal receptors of N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP), cytosolic proteins essential for membrane transport. The expression of these SNAP receptors was investigated by immunoblotting in clonal endocrine cells; catecholamine-secreting adrenal medullary cells (PC12), growth hormone-secreting pituitary cells (GH3), and insulin-secreting pancreatic beta-cells (RINr and RINm5F). All of these receptors as well as NSF and SNAP are expressed in these cells and, co-immunoprecipitation experiments indicate that syntaxin is associated with SNAP-25 and synaptobrevin after solubilization. These results suggest that syntaxin, SNAP-25, and synaptobrevin form a complex and are involved in the secretion of hormones from endocrine cells by exocytosis. PMID- 7777200 TI - The role of acetate as a potential mediator of the effects of ethanol in the brain. AB - Acetate is the primary product of ethanol catabolism and can accumulate in the blood at concentrations of up to 2 mM following ethanol consumption. It has been suggested that some of the pharmacological actions of ethanol are mediated via acetate, which can lead indirectly to the release of endogenous adenosine. In the present experiments this hypothesis was tested by examining the effects of exogenous sodium acetate on the physiology of hippocampal slices from rat brain. Acetate had no significant effect on intracellular responses recorded from CA1 pyramidal neurons or on extracellular field potentials evoked from the either the CA1 region or the dentate gyrus. There was also no significant difference in responses to the adenosine receptor antagonist theophylline in CA1 pyramidal neurons recorded using intracellular filling solutions containing potassium acetate, KCl, or potassium methylsulfate. These results suggest that the presence of acetate, either in the extracellular medium or within an intracellular electrode, does not induce a significant increase in adenosine receptor activation in the hippocampus. PMID- 7777201 TI - Decreased interleukin-6 level in the cerebrospinal fluid of patients with Alzheimer-type dementia. AB - We examined IL-6 levels in the cerebrospinal fluid (CSF) of patients clinically diagnosed with Alzheimer-type dementia (ATD) and with vascular dementia (VD) and of age-matched normal subjects. The IL-6 levels in the CSF of ATD, but not VD patients, were significantly decreased. In the early onset ATD patients (disease onset < 65 years), IL-6 levels were reduced to 21% of the control level. The IL-6 levels in the CSF were not associated with the severity of the dementia or the duration of the disease since the identification of the first symptoms. PMID- 7777202 TI - Human recombinant IGF-I induces the functional expression of AMPA/kainate receptors in cerebellar granule cells. AB - We have previously reported that an excitatory amino acid resistant phenotype (EAA-) of rat cerebellar granule cells becomes EAA sensitive (EAA+) when cultured in the presence of human recombinant IGF-I. In order to assess the mechanism through which this somatomedin upmodulates the functional expression of EAAs receptors, we have performed studies using the whole-cell configuration of the patch-clamp technique to study macroscopic currents evoked by the application in the bath of kainate to (EAA-) and (EAA+) neurons, and compared their properties to sister cultures grown in classical conditions employing whole foetal calf serum (FCS). Kainate elicited macroscopic, 6-cyano-7-nitroquinoxaline-2,3-dione sensitive, inward currents at a holding potential of -60 mV in almost all the patched cells but the mean amplitude of the current was consistently smaller in (EAA-) neurons compared to (EAA+) neurons although the amplitude was still smaller than that observed in FCS-cultured neurons. The amplitude of the responses induced by kainate was a linear function of the membrane potential in the three groups of cells and the reversal potential of the currents was about 0 mV, suggesting that the general property of each channel is identical in all three types of neurons while the different conductances observed are due either to a decreased expression, a different permeability or an altered affinity of the single receptor. PMID- 7777203 TI - Influence of intracisternal injection of somatostatin analog receptor subtypes 2, 3 and 5 on gastric acid secretion in conscious rats. AB - Somatostatin (SST) and its analogs injected into the CSF induce different gastric acid response patterns. Five SST receptors have been characterized (SSTR-1 to 5). We studied the influence of selective SSTR-2, -3 and -5 ligands on basal gastric acid secretion after intracisternal (i.c.) injection in conscious rats equipped with chronic gastric and i.c. cannulae. Compared with pre-injection level, the SSTR-3 agonist, BIM-23056 (1 microgram) increased acid secretion by 274 +/- 43% while the SSTR-2 agonist, DC 32-87 (1 microgram) inhibited acid secretion by 50.7 +/- 13.3%. SST-14 (1 microgram), the SSTR-5 agonist, BIM-23052, (0.5-1 microgram), SSTR-3 (0.5 micrograms) and -2 (0.5 microgram) or vehicle injected i.c. did not modify basal acid secretion. These results show that the activation of brainstem SSTR-3 receptors stimulate and SSTR-2 inhibit basal gastric acid secretion in conscious rats with chronic gastric fistulae. PMID- 7777204 TI - Developmental expression of the neural adhesion molecule F3 in the rat brain. AB - We cloned a cDNA encoding rat F3 and analyzed the nucleotide sequences. The results have shown that rat F3 is comprised of 1021 amino acid residues. It shared 99% and 76% identities with mouse and chicken homologs, respectively, at the amino acid sequence level. During postnatal development of the rat brain, cells expressing F3 mRNA appeared in the cortex, hippocampus, superior and inferior colliculi, anterior olfactory nucleus, olfactory bulb and cerebellum, whereas little was observed at postnatal day 1 (P1). Extraordinarily high expression of F3 mRNA was observed in the cerebral cortical neurons of layer 5 at P7. The number of cells with high expression of F3 mRNA expanded to the entire region of the cerebral cortex at P14. The whole cerebrum displayed expression at P90 in which the cortex still showed the highest expression level, although the overall signals were weak in comparison with those at P14. In the hippocampal formation, F3-expressing granule cells of the dentate gyrus were restricted to the outer aspect, then expanded to the inner aspect during development. Finally the granule cells in the entire region of the dentate gyrus transcribed F3 mRNA. We discuss the significance of the expression pattern of F3 mRNA during development. PMID- 7777205 TI - Axonal projections of utricular afferents to the vestibular nuclei and the abducens nucleus in cats. AB - Axonal projections of utricular (UT) afferents in cats were examined by three approaches: recordings of field potentials, labelling of UT nerve fibres by localized infusion of horseradish peroxidase (HRP) and intraaxonal infusion of HRP into a single UT afferent. UT afferents project principally into the rostral part of the descending nucleus and the ventral part of the lateral nucleus. Projection into the superior and the medial nuclei and the ipsilateral abducens nucleus were also observed. PMID- 7777207 TI - ATP release evoked by isoprenaline from adrenergic nerves of guinea pig atrium. AB - Mode and site of release of ATP evoked by isoprenaline were evaluated in the electrically driven left atrial segment of guinea pig. The peak release of ATP 5 min after 1 microM isoprenaline was inhibited by 1 microM propranolol and 1 microM butoxamine, but not by 1 microM atenolol, showing that the ATP release is due to stimulation of the presynaptic beta 2-adrenoceptor by isoprenaline. The maximum ATP release was markedly reduced by Ca2+/calmodulin antagonists, W-7 and trifluoperazine, and by a mitotic inhibitor, vinblastine. Further, the release was similarly inhibited by myosin light chain kinase inhibitors, ML-7 and wortmannin. Nifedipine, a Ca(2+)-channel blocker, decreased the release of ATP evoked by isoprenaline. By contrast, Bay K 8644, a Ca(2+)-channel opener, tended to enhance the ATP release. These findings suggest that isoprenaline produces ATP release from adrenergic nerve terminals of atrium, implying that ATP serves as a co-transmitter. PMID- 7777206 TI - Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. AB - The neuronal cannabinoid receptor clone was expressed of saturable [3H]WIN 55,212 2 binding sites. Co-expression of the cannabinoid receptor with cRNA coding for the G-protein-gated inwardly rectifying K+ channel (GIRK1) resulted in oocytes exhibiting large inward K+ currents in response to the cannabinoid agonist WIN 55,212-2. The activation of the potassium current by WIN 55,212-2 was dose dependent with an EC50 of 630 nM. These results suggest that activation of inwardly rectifying K+ channels may be an additional effector mechanism for brain cannabinoid receptors. PMID- 7777209 TI - Visionary, creative nurse executive leaders. PMID- 7777208 TI - Autoradiographic study of mitochondrial complex I and glutamate receptors in the basal ganglia of rats after unilateral subthalamic lesion. AB - A unilateral lesion of the subthalamic nucleus (STN) induced, in the short-term (< or = 1 week), an ipsilateral decrease in [3H]dihydrorotenone binding to complex I in entopeduncular nucleus and substantia nigra pars reticulata (SNr). A slight reduction of [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptors in the ipsilateral SNr was also found, whereas no changes in [3H]alpha-amino-3 hydroxy-5-methylisoxazole propionic acid binding were observed. The complex I decrease likely reflects a reduction in neuronal activity subsequent to the interruption of excitatory signaling from STN. The unexpected decrease in [3H]MK 801 binding in SNr may be related to presynaptic NMDA receptor modifications. PMID- 7777210 TI - Managed care and health care reform. PMID- 7777211 TI - Dollars and sense in health reform: interdisciplinary practice and community nursing centers. AB - Historically, community nursing centers (CNCs) provided care to underserved populations, and today they are reemerging to provide accessible, nurse-managed care in urban and rural settings. The quality and cost-effectiveness of care provided by advanced practice nurses in a managed-care environment is described using the Neuman Systems Model. Significant documentation from the literature underscores the value of nurse-managed care, but supports the need for interdisciplinary practice. CNC primary and preventive care in a "center without walls" is described and promoted for accessible, cost-effective and quality care in the context of health care reform. PMID- 7777212 TI - Beyond shared governance: restructuring care delivery for self-managing work teams. AB - Shared governance organizations have been highly successful in empowering nurses for professional practice. They have been more uneven in their effectiveness for solving day-to-day operational problems, however. This article discusses limitations of the traditional approaches and describes a process to develop self managing teams through patient care redesign. Milestones in the evolution of self managing teams are illustrated through a description of experiences at Presbyterian Hospital of Dallas over the past five years. Practical suggestions for the transition to self-managing work teams are outlined. PMID- 7777213 TI - Role restructuring: nurse, case manager, and educator. AB - A quality improvement team of nursing managers and staff nurses planned and implemented a new delivery system that combines a team nursing method of care delivery and a unit-based case manager. The new unit-based case manager role is unique because in addition to case management, the role is also responsible for the education of staff on an assigned unit and meeting the educational needs of patients/families. The role has proved to be cost effective and has improved patient outcomes. This model is an effective delivery system for hospitals with limited resources for bedside care. PMID- 7777214 TI - The Queen's Medical Center Honolulu, Hawaii. AB - The Queen's Medical Center created and almost fully realized a vision of professional nursing practice. This vision was mission-driven and philosophically oriented in that our Hawaiian heritage and commitment to a patient-centered focus dictated the direction taken. Utilizing the nursing process, we listened to our patients in identifying the nursing model to best meet their needs: primary nursing. In order to achieve that, the nurse at the bedside had to be empowered to make decisions directly impacting patient care. We further committed to treating the whole patient and considering complementary therapies. We have established an evaluation baseline and are committed to a process that will carry us into the year 2000. PMID- 7777215 TI - Differentiated practice: the new paradigm using a theoretical approach. AB - Differentiated practice is a term that has been identified in nursing for years. Nurses today, however, still practice under the old paradigm that disregards preparation and states that "a nurse is a nurse is a nurse." The idea of differentiated practice, which supports the restructuring of nursing roles based on education, experience, and competence, can again be found in recent literature. Current models for differentiated practice and rationales for implementation are reviewed. This article addresses the need to shift from the old paradigm and provides an analysis of the issues central to differentiated practice from two theoretical perspectives: role theory and nursing theory. PMID- 7777217 TI - Technology and managed care. PMID- 7777216 TI - Nursing care delivery models and nurse satisfaction. AB - The relative impact of various nursing care delivery models and management interventions on nurse satisfaction was assessed in 37 New Jersey hospitals. Nurses ranked pay as the most important factor, followed by autonomy and professional status. Changes in scores between pilot and comparison units were significantly different for satisfaction with interactions and task requirements. Change in satisfaction with interaction was significant for all initiatives in aggregate, as well as for each of the five types of initiatives separately. The change in satisfaction with task requirements was significant for all initiatives taken as a group and for those units that implemented reorganization, computer, and education initiatives. Even among nurses who eventually liked the new environment there was a period of initial dissatisfaction. PMID- 7777218 TI - Relationship among subjective mental workload, experience, and education of cardiovascular critical care RNs. PMID- 7777219 TI - Sharpening of frequency tuning by inhibition in the central auditory system: tribute to Yasuji Katsuki. AB - Frequency analysis is a fundamental function of the auditory system. Bekesy and Katsuki believed that sharpening of frequency tuning by lateral inhibition takes place in the central auditory system. However, most 'cat' auditory physiologists have believed that frequency tuning of neurons is not sharpened in the central auditory system, so that there is no lateral inhibition. Unlike quasi-triangular frequency-tuning curves of peripheral neurons, pencil- or spindle-shaped frequency-tuning curves have been found in the central auditory systems of many species of animals belonging in different classes. Inhibitory tuning curves are commonly associated with such 'level-tolerant' sharp excitatory tuning curves. It is that frequency-tuning curves of some central auditory neurons are sharpened by inhibition. Yasuji Katsuki (Professor, M.D., Ph.D.) passed away on 6 March 1994 at the age of 88. I have written this article as a tribute to him, focusing on his major contribution to auditory neurophysiology: the finding of the sharpening of frequency tuning in the cat's central auditory system. Neural sharpening of frequency tuning is an old yet still current topic, as you will read in this article dedicated to Professor Katsuki. PMID- 7777220 TI - Influences on the gamma-muscle-spindle system from contralateral muscle afferents stimulated by KCl and lactic acid. AB - The aim of the present study was to investigate whether increased concentrations of lactic acid and potassium chloride (KCl) in contralateral muscles can influence the sensitivity of primary and secondary muscle spindle afferents (MSAs) from ipsilateral extensor and flexor muscles. The experiments were performed on 7 cats anaesthetised with alpha-chloralose. Recordings were made simultaneously from 2-12 single MSAs from the triceps surae (GS) and/or the posterior biceps and semitendinosus muscles (PBSt). The mean rate of firing and the amplitude of a fitted sine curve of MSA responses to sinusoidal stretching of the receptor bearing muscles were determined. Responses of 42 primary MSAs (17 from PBSt and 25 from GS) were recorded. On 33 of these, clear-cut alterations in sinusoidal response were evoked by injection of 1 ml KCl (200-400 mM) or 1 ml lactic acid (20-50 mM) into the arterial supply of the contralateral GS or PBSt muscles. Six out of 8 secondary MSAs showed sizeable effects to increased intramuscular concentrations of KCl and/or lactic acid (3 from PBSt and 3 from GS). On both primary and secondary MSAs, from GS as well as from PBSt muscles, the large majority of effects were excitatory. All effects on secondary MSAs were compatible with reflex actions on static fusimotor neurones, whereas on primary MSAs different types of reflex responses were observed (i.e. pure static, pure dynamic and mixtures of static and dynamic fusimotor actions). Stimuli related alterations in MSA responses were completely abolished when the contralateral GS or PBSt nerves were anaesthetised.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777222 TI - Roles of GABAA, NMDA and muscarinic receptors in induction of long-term potentiation in the medial and lateral amygdala in vitro. AB - We have studied mechanisms underlying long-term potentiation (LTP) in the medial and lateral amygdala using in vitro slice preparations. In normal bathing medium, LTP was not induced by tetanic stimulation (100 pulses at 100 Hz). However, in the presence of a GABAA blocker, picrotoxin or bicuculline, LTP was reproducibly induced in both medial and lateral amygdala. In the medial amygdala, the LTP induced in the presence of picrotoxin was blocked by 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and was significantly reduced by scopolamine, a muscarinic receptor antagonist. On the other hand, the LTP in the lateral amygdala was not affected by APV, but was significantly reduced by scopolamine. These results suggest that both NMDA receptors and muscarinic receptors are involved in the induction of medial amygdala LTP, while muscarinic receptors, but not NMDA receptors, are involved in the induction of lateral amygdala LTP. PMID- 7777221 TI - Effects of long-term administration of phenelzine on reticular-elicited hippocampal rhythmical slow activity. AB - All anxiolytics so far tested show a common reduction in the frequency of reticular-elicited hippocampal rhythmical slow activity (RSA). Acute administration of the tricyclic antidepressant imipramine shares this effect with anxiolytics. The present experiment tested whether the MAO inhibitor antidepressant phenelzine shares this common effect of anxiolytics and imipramine on hippocampal RSA. Rats, implanted with reticular stimulating electrodes and subicular recording electrodes, received four acute doses (0.2, 2.0, 6.0 and 18 mg/kg) or one chronic dose (2 mg/kg/day for 35 days) of phenelzine. Acute administration of phenelzine failed to systematically affect RSA frequency. Chronic injections of phenelzine eventually produced a reduction in RSA frequency combined with a gradual increase in baseline RSA frequency. The absence of immediate action and the production of a chronic reduction in RSA frequency are distinct from the documented effects of anxiolytics and imipramine, whereas the increase in baseline RSA frequency is similar to imipramine. The different influence of phenelzine on RSA frequency compared with anxiolytics (including imipramine) is consistent with the different clinical profiles of these drugs. PMID- 7777223 TI - Noradrenaline inhibits preoptic sleep-active neurons through alpha 2-receptors in the rat. AB - Effects of noradrenaline (NA) on the activity of sleep-related neurons in the preoptic area (POA) and the neighboring basal forebrain were examined in the rat. Of 36 sleep-active neurons tested, 19 were inhibited and the other 17 were unaffected by NA applied through a multibarrel pipette. The alpha 2-agonist clonidine inhibited 11 of 14 sleep-active neurons and did not affect the other 3 neurons, whereas the alpha 1-agonist methoxamine (n = 13) and the beta-agonist isoproterenol (n = 11) had no effect on any of the sleep-active neurons tested. Thus, alpha 2-receptors mediated the NA-induced inhibition. Of 22 waking-active neurons tested, NA excited 10, inhibited 1, and had no effect on the remaining 11. Methoxamine excited 4 of 13 waking-active neurons tested, whereas isoproterenol (n = 9) and clonidine (n = 4) were without effect on any of the waking-active neurons tested. Accordingly, alpha 1-receptors probably mediated the NA-induced excitation. Seventy-seven state-indifferent neurons, which lacked activity related to the sleep-waking state, and 20 paradoxical sleep-active neurons were mostly (65%-70%) insensitive to NA. These results suggest that NA promotes wakefulness by inhibiting sleep-active neurons and by exciting waking active neurons. PMID- 7777224 TI - Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta. AB - Postsynaptic responses of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) to stimulation of the pedunculopontine tegmental nuclei (PPN) were studied in in vitro slice preparations in the rat. The recorded neurons were intracellularly injected with biocytin and also identified as DA neurons by an immunocytochemical technique. PPN stimulation induced in DA neurons monosynaptic excitatory postsynaptic potentials (EPSPs) that consisted of early transient and slow components. An application of anti-glutamatergic agents (1 mM kynurenic acid and/or 30 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) in the bathing media partially suppressed the EPSPs, indicating that PPN inputs to SNc DA neurons are glutamatergic and non-glutamatergic. Anti-glutamatergic resistant EPSPs were suppressed by applications of anti-cholinergic agents such as atropine, mecamylamine, and pirenzepine. These data indicate a convergence of glutamatergic and cholinergic excitatory inputs from the PPN to SNc DA neurons and that both nicotinic and muscarinic receptors are involved in the cholinergic transmission. PMID- 7777226 TI - Campaign sends wrong message. PMID- 7777225 TI - Projection of cardiovascular afferents to the lateral nodulus-uvula of the cerebellum in rabbits. AB - Vagal and aortic afferent projections to the nodulus and uvula of the cerebellar vermis were examined in anesthetized and paralysed rabbits. Electrical stimulations of vagal and aortic nerves at a frequency of 1/s produced field potentials in the lateral cortical region of the contralateral nodulus-uvula with a latency of 6.5-19 ms. These potentials were negative in the molecular layer and positive in the granular layer. At a higher stimulation rate (30/s), these potentials were reduced by 60-65% of the control value. These results indicate that the lateral cortical region of the nodulus-uvula receives contralateral vagal and aortic afferent signals via climbing fibers. Electrical stimulation of vagal nerves also produced field potentials in the lateral region of the ipsilateral nodulus-uvula with a latency of 6-10.5 ms. Their laminal profile was characteristic of mossy fiber responses. At a higher stimulation rate (30/s), the reduction of these potentials was only 35%. Thus the lateral nodulus-uvula also receives the ipsilateral vagal afferent signals via mossy fibers. Following injection of horseradish peroxidase into the small areas of the lateral nodulus, labeled cells were found in bilateral intercalatus nucleus, prepositus hypogrossal nucleus, Roller nucleus, medial fascicullus longitudinalis, and medial and lateral vestibular nuclei. These nuclei may contain precerebellar neurons in the pathway from the vagal nerve to the lateral nodulus-uvula via mossy fibers. PMID- 7777227 TI - A second opinion. PMID- 7777228 TI - Informed consent. What it is, why it is. PMID- 7777229 TI - Implications for the practice of dentistry. PMID- 7777232 TI - IOM report on dental education is standard for the future. PMID- 7777231 TI - The Columbia experience. PMID- 7777230 TI - Patient-centered education. The NYU experience. PMID- 7777233 TI - A teacher's guide to the future of dental education. PMID- 7777234 TI - Steps in the right direction. A private practitioner's perspective. PMID- 7777236 TI - Continuing education brings its own rewards. PMID- 7777235 TI - UB researchers study mouthwashes and osteoporosis/gum disease link. PMID- 7777238 TI - Prognostic significance of necrosis, elastosis, fibrosis and inflammatory cell reaction in operable breast cancer. AB - We analyzed retrospectively the relationships and the prognostic significance of four anatomopathological features (elastosis, fibrosis, necrosis, inflammatory cell reaction) of the primary tumor in a series of 1,457 cases of infiltrating ductal carcinoma observed at our institution from January 1978 to December 1991. Necrosis, elastosis, fibrosis and inflammatory cell reaction were strongly associated among themselves (all p < 0.0001), the only exception being necrosis and elastosis. Necrosis was significantly related to tumor size (odds ratio [OR] = 5.40, p < 0.0001) and tumor grade (OR = 2.22, p < 0.0001). Univariate analysis showed that the presence of necrosis and cell reaction were significantly related to worse survival (p < 0.0001 and p = 0.03, respectively). Multivariate analysis, including the four variables plus nodal status, tumor size, grading, adjuvant therapy, age and first order interactions, revealed that greater tumor size (p < 0.0001), positive nodal status (p < 0.0001), higher histologic grade (p < 0.0001) and presence of inflammatory cell reaction (p = 0.0007) independently worsened survival. On the other hand, adjuvant therapy had a significant independent role in preventing deaths (p = 0.03). The only first-order interaction retained in the model was that between grading and cell reaction (p = 0.002). Cell reaction had a different prognostic behaviour in the groups G1-G2 and G3: in the former group, survival was worse (p = 0.0001) when the inflammatory cell reaction was present. In conclusion, we demonstrate that cell reaction is an independent prognostic factor in the G1-G2 subgroup of patients, and propose a hypothesis as to the role of cell reaction in primary breast cancer. PMID- 7777237 TI - The role of fatty acids and eicosanoid synthesis inhibitors in breast carcinoma. AB - We have reviewed the literature concerning the role of fatty acids and eicosanoid synthesis inhibitors in breast carcinoma. The omega-6 polyunsaturated fatty acids (PUFAs), primarily linoleic acid, promote breast cancer tumorigenesis and tumor cell proliferation directly and indirectly via increased synthesis of cyclooxygenase- and lipoxygenase-catalyzed products. The omega-3 PUFAs, primarily docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), suppress breast carcinoma tumorigenesis and tumor cell proliferation, although the effect of DHA may be partly ascribed to increased amounts of EPA derived from DHA. Both cyclooxygenase and lipoxygenase inhibitors suppress tumorigenesis and/or tumor proliferation, with the latter being more active. Thus, arachidonic acid-derived eicosanoids play an important role in breast cancer, and the balance of the various eicosanoids may be a critical determinant of cell proliferation. However, the exact mechanism by which fatty acids and eicosanoid synthesis inhibitors exert stimulatory and inhibitory effects on breast carcinoma is still not well understood. PMID- 7777239 TI - Serial transplants of DMBA-induced mammary tumors in Fischer rats as model system for human breast cancer. IV. Parallel changes of biopterin and melatonin indicate interactions between the pineal gland and cellular immunity in malignancy. AB - Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer. PMID- 7777240 TI - Relapse of Hodgkin's disease after ten years. AB - We report four cases of Hodgkin's disease (HD) relapsing after complete remission for over a 10-year period after the initial therapy. Three of the patients had mixed-cellularity subtypes as a primary histological diagnosis, and the rebiopsies demonstrated mixed cellularity in all very late relapse cases. Two patients were initially treated with radiotherapy, while in the other two advanced cases polychemotherapy was administered. All patients had advanced disease at the time of the very late relapses, though the relapse was not identifiable in the previously involved regions. By rescue therapy, all patients achieved a second complete remission. However, two patients relapsed again with one of them dying during relapse. The three remaining patients are still in complete remission. Our report demonstrates the necessity of prolonged follow-up of patients with HD. PMID- 7777242 TI - Severe cardiotoxicity of high-dose 5-fluorouracil in combination with folinic acid, cisplatin and methotrexate in a 14-year-old boy with nasopharyngeal carcinoma (Schmincke tumor). AB - Cardiotoxicity by 5-fluorouracil has been reported as a rare complication in treatment protocols for adult patients with different malignant diseases. The combination with folinic acid as a biomodulatory substance and other cytotoxic drugs has been introduced to render protocols more effective and less toxic. We report severe but completely reversible cardiotoxicity of a treatment protocol for nasopharyngeal tumor (Schmincke tumor) of pediatric patients consisting of 5 fluorouracil, methotrexate, cisplatin and folinic acid in a 14-year-old boy who had no preexisting cardiac disease. The pathomechanism is briefly discussed. PMID- 7777243 TI - The efficacy of continuous local arterial infusion of 5-fluorouracil and cisplatin through an implanted reservoir for severe advanced hepatocellular carcinoma. AB - There is not yet an effective standard therapy for severe advanced hepatocellular carcinoma (HCC). We attempted continuous local arterial infusion chemotherapy using 5-fluorouracil (5-FU) and cisplatin (CDDP) with an implanted reservoir for these patients, and evaluated its efficacy. Twenty-one HCC patients received continuous arterial infusion of 5-FU and CDDP for 1 week, followed by a 1-week no infusion period; this regimen was repeated 1-32 times, and patients were observed for 36-549 days. The 1-year survival rate was 61.1%, and alpha fetoprotein levels decreased in 13 patients. All could continue as outpatients for 94.0% of the entire course of therapy. Because CDDP amplifies the effect of 5-FU as a biochemical modulator, and because continuous infusion strengthens the effect of 5-FU and reduces the side effects of CDDP, we consider this therapy to be effective for patients with severe advanced HCC, prolonging survival and improving the quality of life. PMID- 7777241 TI - Clinical evaluation of squamous cell carcinoma antigen in squamous cell carcinoma arising in mature cystic teratoma of the ovary. AB - We attempted to assess the clinical utility of squamous cell carcinoma antigen (SCC) for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. SCC in serum from 16 patients with this malignancy and from 56 patients with mature cystic teratoma without malignancy was measured using radioimmunoassay. Serum SCC levels exceeded the cut-off of 2.0 ng/ml in 9 (56%) of the 16 patients with malignancy. This rate was significantly higher than that in the patients with nonmalignant mature cystic teratoma (9 to 56, 16%; p < 0.01). The positive rate for SCC was as low as 30% for stage I cancer. All cases in which the tumor size was > 500 cm3 had a positive response for SCC, whereas all other cases had a negative response (p < 0.001). SCC is useful as a tumor marker for this malignancy. However, the serum SCC level depends on the tumor volume, so it may not be suitable for early detection of small tumors. PMID- 7777244 TI - Effect of adriamycin, 5-fluorouracil and mitomycin-C combination chemotherapy in advanced colorectal cancer. AB - One hundred and seventy-four patients with advanced colorectal cancer were treated with 5-fluorouracil (5-FU), mitomycin-C (MIT-C) and Adriamycin (ADR) (FAM). The total response rate was 26.4%. A higher response rate (37%) was observed in patients with liver metastases only, compared to other sites of metastases (p < 0.02). Complete remission were achieved only in patients with liver metastases (15%). Male patients with liver metastases had a higher response rate than females (p < 0.03). Twenty-five patients previously treated unsuccessfully with 5-FU and MIT-C showed a response rate of 28% when ADR was added to the regimen. The patients' median survival was 11 months (range: from 3 to > or = 60 months). The median survival of patients with liver metastases was 11 months and that of responders (20 months) was significantly longer than that of nonresponders (7 months; p < 0.0001). These results suggest that the FAM combination might be considered an eligible chemotherapy schedule for patients with liver metastatic disease from colorectal cancer. PMID- 7777245 TI - Vanadium: a modifier of drug-metabolizing enzyme patterns and its critical role in cellular proliferation in transplantable murine lymphoma. AB - Vanadium, as ammonium monovanadate, has been found to stimulate tumour cell proliferation in mice bearing a transplantable ascitic lymphoma. Markers including microsomal cytochrome P-450, UDP-glucuronyltransferase and cytosolic glutathione-S-transferase showed substantial alterations in a dose-responsive manner with vanadium administration when compared to the controls. Stimulation of tumour progression is also reflected by increased tumour cell count and decreased survival of the host. PMID- 7777247 TI - Total suppression of spontaneous endometrial carcinoma in BDII/Han rats by melengestrol acetate. AB - Female virgin BDII/Han rats develop spontaneous endometrial carcinoma (EC) in incidences up to 90%. Our objective was to determine whether lifelong administration of the progestin melengestrol acetate (MGA) would suppress those tumors. Four groups of 20 rats aged 24-28 days were employed Group I animals were untreated controls. Groups II, III, and IV were fed 0.1, 0.2, and 0.4 mg MGA/kg daily in their diet during their lifetimes. All treated groups were free from EC during their lifetimes with an increased lifespan up to 30%. The controls, in contrast, had an EC incidence of 85%. Histologically, with one exception all tumors were classified as adenocarcinoma. While most of the control rats died from EC, nearly all animals of groups II and III died from age-related diseases. Rats in group IV showed side effects due to the glucocorticoid properties of MGA. Besides alopecia and obesity an acceleration of chronic progressive nephrosis was observed. The study establishes the validity of the prophylactic approach to spontaneous hormone-dependent cancers in a rat tumor model. PMID- 7777246 TI - Efficacy of ondansetron treatment with different timing schedules: a randomized double-blind study. AB - The purpose of this study was to determine whether preloading administration of ondansetron given 12.5 h before cisplatin therapy, every 6 h, is better in controlling acute cisplatin-induced emesis than a standard dose every 8 h. All patients had previously received three cycles of CDDP-based chemotherapy in a dose of 100 mg/m2. Ondansetron was given according to two schedules: in group A (40 patients) at a dose of 8 mg in 100 ml normal saline over 10 min by intravenous infusion before the infusion of CDDP continued with 1 tablet of 8 mg after 8 and 16 h; in group B (40 patients) it was administered in six intravenous doses (every 6 h) starting 12.5 h before cisplatin administration. During the following 3 days, patients from both groups continued with tablets of 8 mg orally, every 8 h in group A and every 6 h in group B. The only difference in terms of the antiemetic response noticed between the two groups was in the number of patients that presented with nausea, which was increased in group A (32) in comparison to group B (25; p < 0.022). No difference was found in the number of vomiting episodes, retches or control of emesis, during the 3-day evaluation period after cisplatin infusion, and in secondary side effects. In conclusion the total dose of 24 mg ondansetron during the acute phase of emesis is as effective as preloading and increasing the total dose to 32 mg. PMID- 7777248 TI - Dose-finding study of 5'-deoxy-5-fluorouridine in combination with fixed doses of cisplatin and L-folinic acid for the treatment of advanced or recurrent squamous cell carcinoma of the head and neck. AB - In order to assess the maximum tolerated dose of 5'-deoxy-5-fluorouridine (5dFUR) combined with a cisplatin (20 mg/m2 i.v.) and L-folinic acid (100 mg/m2 i.v.), 5 day schedule 19 consecutive chemotherapy-naive patients affected by advanced or recurrent carcinoma of the head and neck were entered in this phase I trial. Doses of 5dFUR were escalated from a starting level of 2,000 mg/m2/day up to 3,000 and 5,000 mg/m2/day. At the latter step the dose-limiting acute toxicities were stomatitis and diarrhea, which were of WHO grade 3-4 and occurred in 3 and 1 out of 4 evaluated patients, respectively. Other grade 3 acute toxicities were leukopenia, anemia, renal impairment, and neurologic symptoms, observed in 1 patient each. Furthermore, one possibly treatment-related death was registered among patients entered in the highest dose level. Eleven out of 19 patients (58%; 95% CI:34-80%) showed a complete (2 cases) or partial (9 cases) response to this treatment, regardless of the 5dFUR dosage employed. From our results we may define the maximum tolerated dose of 5dFUR to be associated with cisplatin and L folin acid used in this trial as 3,000 mg/m2/day x 5 days. Assessment of the real activity of this combination chemotherapy deserves further studies. PMID- 7777249 TI - Mucinous adenocarcinoma arising in the renal pelvis of an ectopic pyelic kidney. AB - A case of mucinous adenocarcinoma probably originating in the renal pelvis of an ectopic pyelic kidney with infiltration of the adjacent urinary bladder is reported. Review of the literature shows that this is the 42nd case of such a tumor, the second one reported in the pelvis of an ectopic pyelic kidney, and the first infiltrating the urinary bladder. PMID- 7777250 TI - Histologic grade and cellular proliferation at the deepest invasive portion correlate with the high malignancy of submucosal invasive gastric carcinoma. AB - To establish appropriate indications for endoscopic treatment of submucosal invasive gastric carcinoma, we investigated clinicopathologic features and proliferating cell nuclear antigen (PCNA) expression at the deepest invasive portion of 192 differentiated submucosal invasive gastric carcinomas that had been surgically resected. Lymph node metastasis was demonstrated in 30 (15.6%) of 192 lesions. Histologic heterogeneity (based on differentiation at the deepest invasive portion) was demonstrated in 36 (18.8%) of the 192 lesions. In 159 lesions, excluding 33 undifferentiated lesions at the deepest invasive portion, the depth of invasion, histologic grade, lymph vessel involvement, infiltrative growth pattern (INF) and existence of an ulceration were all significantly correlated with the incidence of lymph node metastasis. The lesions with both well-differentiated adenocarcinoma (WELL) and minimal submucosal invasion (sm1) showed no lymph node metastasis. PCNA expression was estimated in 59 good stained lesions. The mean PCNA labeling index (LI) was 50.9 +/- 7.2% in lesions with lymph node metastasis and 43.7 +/- 9.3% in those without lymph node metastasis (p < 0.05). In addition, PCNA-LI also correlated significantly with the histologic grade, depth of invasion, INF and lymph vessel involvement. These results indicate that the submucosal invasive gastric carcinoma with both WELL and sm1, which shows no other risk factors, can be considered as the appropriate indication for curative endoscopic treatment. The PCNA-LI at the deepest invasive portion is useful in understanding the biology of lymph node metastasis in submucosal invasive gastric carcinoma. PMID- 7777251 TI - Association of immunohistochemical detection of urokinase-type plasminogen activator with metastasis and prognosis in colorectal cancer. AB - We evaluated urokinase-type plasminogen activator (uPA) expression with immunohistochemistry in 90 cases of colorectal cancer and compared it with the clinicopathological findings. Patients who had cancer cells which were stained intensively relative to the background were recognized as uPA-positive patients. The uPA-positive rate was 36.7% (33/90) in total cases. There was a significant correlation was also seen between uPA expression and liver metastasis. Prognosis was poorer in the uPA-positive patients than in the uPA-negative patients. Therefore, uPA may be a good predictor of metastasis and prognosis. PMID- 7777252 TI - [The effect of the duration of culturing on the pluripotency of mouse embryonic stem (ES) cells in vitro and in vivo]. AB - A comparative analysis of two clones of mouse embryonic stem cells (ES-D3) that underwent different number of passages was performed to determine their potencies for in vitro and in vivo development. Cells of both clones had similar morphology characteristic of undifferentiated ES cells and were capable of forming embryoid bodies in the suspension cultures. Specific alkaline phosphatase activity of ES cells was revealed by cytochemical staining. Karyotyping showed that the proportion of aneuploid ES cells increases with an increase in the number of passages. The results of experiments on chimera production using ES cells showed that the clone D3W (passage 17) is superior to the clone D3M (passage 42) in terms of both the proportion of chimeras produced and the degree of coat color chimerism in them. PMID- 7777254 TI - [An electron microscopic study of the structure of the indirect flight musculature at the pupal stage in the muscle mutant of Drosophila melanogaster]. AB - Ultrastructure of indirect flight muscles was analyzed in Drosophila pupae heterozygous for the mutation l(2)MhcM66, which is an allele of the locus Mhc (Myosin heavy chain). It is demonstrated that the initial stages of muscle fiber differentiation in mutants proceed normally. First visible changes (elimination of individual thick protofibrils) are observed when myofibrils attain a certain size. Disintegration of the contractile apparatus progresses with growth of myofibrils. Mechanisms responsible for onset and development of these destructive processes during ontogeny are discussed. PMID- 7777255 TI - [The functional characteristics of the beta 2-adrenoreceptors on the isolated membranes and intact erythrocytes of rats]. AB - The main parameters of [3H]-propranolol binding were determined for beta adrenoreceptors of membrane preparations and intact erythrocytes of white rats. It was shown that two molecules of [3H]-propranolol bind to one beta adrenoreceptor. Two pools of adrenoreceptors differing in their affinity to the ligand and their number on the erythrocyte membrane were identified. In experiments on ligand binding to intact erythrocytes, dissociation constants (Kd) of high-affinity and low-affinity pools differed by a factor of 17 (0.92 +/- 0.22 and 15.39 +/- 2.69 nM, respectively); the number of receptors per cell differed by a factor of 9 (28 +/- 6 and 258 +/- 58). The maximal number of adrenoreceptors per erythrocyte was 286 +/- 57. In experiments with erythrocyte membrane preparations, dissociation constants of high-affinity and low-affinity pools differed by a factor of 25 (0.74 +/- 0.04 and 18.47 +/- 0.71 nM, respectively). The number of binding sites for the ligand differed by a factor of 3 (15.88 +/- 7.53 and 71.55 +/- 43.68 fmoles/mg protein, respectively). The main parameters of the ligand-receptor interaction obtained using two methods gave similar quantitative characteristics of the functional activity of erythrocyte beta adrenoreceptors. PMID- 7777253 TI - [The cloning of fragments of homeobox genes expressed during planarian regeneration]. AB - The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WFQNRR) of the Antennapedia class homeodomain was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), were obtained. Their comparison with other homeobox genes using a "Genebee" software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily that includes mouse mesodermal homeobox genes Mox-1 and Mox-2 and rat homeobox gene Gax. PMID- 7777256 TI - [The activity of melanin-aggregating hormones in the blood and eyes in the early postnatal development of rats]. AB - The activity of melanin-aggregating hormones (MAH) in the blood serum and homogenates of the eyes in four strains of rats was determined using the method of bioassay on dermal melanophores of tadpoles (Rana temporaria). This test system is sensitive to melatonin at concentration of 25.1 mg/ml and higher. MAH is detected in the blood at 9th and in eye homogenates at 15th days after birth in grey Norway rats, while in albino Wistar and pale hooded Campbell rats with hereditary retinal degeneration MAH is observed at the 3rd and 4th postnatal days respectively. No increase of MAH activity is found in black hooded Hunter rats with inherent retinal degeneration during the first five days after birth. Thus, Wistar and Campbell rats differ significantly from grey and Hunter rats by MAH activity in the blood and eyes during early postnatal development. PMID- 7777257 TI - [The effect of para-aminobenzoic acid on the level of proliferative activity in the regenerating cornea of adult rats (a radioautographic study)]. AB - [3H]-Thymidine radioautography showed that 0.005% p-aminobensoic acid (PABA) solution applied three times per day on penetrating wounds in central part of the adult rat cornea selectively stimulates proliferative activity of corneal stroma keratoblasts. In control rats, a curve showing changes in index of labeled nuclei in corneal stroma had two peaks, on the second and sixth day after injury (about 5 and 3%, respectively), whereas in animals receiving PABA treatment it had a single peak on the second day (about 12%). On days 7-14, indices of labeled nuclei in corneal stroma of both experimental and control rats become similarly low. No difference between experimental and control animals was revealed in indices of labeled nuclei in corneal epithelium: in both groups, corresponding curves had two peaks (about 9%) on the first and fifths days, and proliferation still continued two weeks after injury. PMID- 7777258 TI - [The theory of germ layers: the debatable aspects]. AB - Data on early embryonic development of animals provided the basis for the following conclusions. In most (if not in all) species, germinal layers are not primitive structures recapitulating the initial organs of ancestral forms. The initial cell differentiation in the embryo is not directly associated with gastrulation, and the common concept of a fundamental relationship between germinal layer formation and cell differentiation is erroneous. Specification of cell types during early development and morphogenetic movements during gastrulation are relatively autonomous processes controlled by different genetic systems. The formation of germinal layers during individual development of different multicellular animals can be understood taking into account that segregation of cell layers is an essential element of epithelial morphogenesis. Movement of cells and cell layers during gastrulation is a specific manifestation of a general morphogenetic principle. PMID- 7777259 TI - [The nature of a nuclear growth-inhibiting factor]. PMID- 7777260 TI - [Enzymes of the antioxidant system in the postnatal ontogeny of mink]. AB - The activity of the key antioxidant enzymes, superoxide dismutase and catalase, was estimated in various organs of mink (Mustela vison Briss.) pups during postnatal ontogenesis. The organ-specific distribution of these enzymes was established and the levels of their activity were matched to certain periods of ontogenesis. This enzymatic system is already formed by the moment of birth, and further changes in it are related to the growth of organs and the effects of environmental factors. PMID- 7777261 TI - [Dimensionless criteria of the time for the development of Drosophila embryos, larvae and pupae and of bee embryos in tables of normal development]. AB - The work reported in this paper constitutes the first attempt to apply the method of the dimensionless characteristic of development duration (Dettlaff and Dettlaff, Arch. Biol. (Liege), 1961, vol. 72, pp. 1-16) to insects, specifically Drosophila melanogaster and Apis mellifera. PMID- 7777262 TI - [The role of chlorine ions in progesterone production and oocyte maturation induced by a pituitary suspension in the follicles of the common frog]. AB - Chloride channel blockers SITS (4-acetamido-4'-isothiocyanostilbene-2,2' disulphonic acid) and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) significantly suppressed progesterone production (0.01-10 microM) in Rana temporaria follicle-enclosed oocytes and oocyte maturation (0.1-10 microM) stimulated by the homologous pituitary suspension (0.00125-0.005 pit/ml). Inhibition was dose-dependent. SITS (1 and 10 microM) did not affect the production of progesterone stimulated by dibutyrylcyclic AMP (2 and 3 mM). The substitution of chloride salts for equimolar concentrations of corresponding gluconates or of sodium chloride for sodium methanesulfonate also significantly increased the production of progesterone stimulated by the pituitary suspension (0.00125-0.0025 pit/ml) and its production in the intact follicle-enclosed oocytes in four out of six females. The reduction of extracellular chloride concentration significantly potentiated the "spontaneous" maturation of oocytes of all females. PMID- 7777263 TI - [Sex differences in the consequences of the hormonal treatment of male rats for their progeny]. AB - The effects on male rats of single injections of androgens have been shown; this paper considers the responses of the immune and genital systems. The consequences for the progeny, with special reference to their sex and age, of androgenization of the father are considered in a comparative aspect. Deviations have been recorded in physical and sexual development, as well as in the genital system, in the progeny of both sexes. Furthermore, the male progeny is characterized by increased reactivity of the thymus. PMID- 7777265 TI - [The preservation of mammalian ova and embryos at positive near-zero temperatures. II. The general patterns and mechanisms of hypothermic exposure]. AB - General patterns of the sensitivity of embryos to hypothermia are described, such as its species-specific dependence, its relationship with the embryonic stage, etc. Data are provided on differences in the cold resistance of the inner cell mass and trophectoderm cells, as well as that of the nucleus and cytoplasm. The mechanisms underlying the effects of cold on mammalian eggs and embryos are considered, and ways of improving the method of hypothermic storage are discussed. The general technological principles of the storage of mammalian embryos at positive near-zero temperatures are formulated for the first time. Advantages and drawbacks of the method and its possible practical application are discussed. PMID- 7777264 TI - [The level of sex steroids in the blood of inbred-strain mice during a normal pregnancy and after zygote retransplantation]. AB - The effect of genotypes on the blood content of progesterone and estradiol was studied in female CBA, C57BL and BALB mice. We also studied progesterone content at the early stages of pregnancy after the effect of stress factors, such as narcosis and surgery, involved in the retransplantation of the embryo from the donor to the recipient. The levels of sex hormones increased during pregnancy with two peaks on the 6-8th and 14-18th days. The pattern of changes in the level of both hormones depends on the female genotype: at some stages, reliable interstrain changes in the blood content of both progesterone and estradiol were found. At the same time, narcosis and bilateral laparotomy did not affect the blood level of progesterone within 12 h after mating, despite marked activation of the adrenocortical system. The data obtained should be taken into account when selecting mother-fetus pairs for retransplantation of embryos in experimental and farm animals. PMID- 7777266 TI - Persisting temporal arteritis. PMID- 7777267 TI - Blood glucose control and vision outcome in diabetes. PMID- 7777268 TI - Endophthalmitis after pars plana vitrectomy. The Postvitrectomy Endophthalmitis Study Group. AB - PURPOSE: To describe the clinical course and incidence of culture-proven postvitrectomy endophthalmitis in 18 patients from five academic centers and three private practices. METHODS: Patients undergoing pars plana vitrectomy for recent trauma or endophthalmitis were excluded. The average age was 58 years (range, 21-85 year). Sixty-one percent of the patients (11/18) had diabetes mellitus. The indication for initial vitrectomy was vitreous hemorrhage (n = 10), macular epiretinal membrane (n = 3), recurrent retinal detachment with proliferative vitreoretinopathy (n = 2), retinal detachment with retinoschisis (n = 1), proliferative diabetic retinopathy with tractional retinal detachment (n = 1), and dislocated intraocular lens (n = 1). None of these eyes received prophylactic intraocular antibiotics during the vitrectomy. RESULTS: All eyes were treated with intraocular antibiotics after the diagnosis of postvitrectomy endophthalmitis was made. Final visual acuity ranged from 20/20 to no light perception and included five eyes with 20/50 or better visual acuity and 11 eyes with less than 5/200 visual acuity. Nine eyes had a final visual acuity of no light perception. Of the 16 eyes infected with a single organism, 71% (5/7) of eyes infected with coagulase-negative staphylococci retained 20/50 or better final visual acuity compared with no eyes (0/9) infected with other organisms (P = 0.005). Two eyes infected with both coagulase-negative Staphylococcus and Streptococcus had a final visual acuity of 20/400. Three eyes with a total hypopyon later had enucleation or evisceration. Based on the data from four medical centers, the incidence of endophthalmitis after pars plana vitrectomy performed over the last 10 years was 9/12,216 (0.07%). CONCLUSION: Endophthalmitis after vitrectomy is rare. Postvitrectomy bacterial endophthalmitis caused by organisms other than coagulase-negative staphylococci has a poor visual prognosis. PMID- 7777269 TI - Proptosis as the initial presentation of fungal sinusitis in immunocompetent patients. AB - BACKGROUND: Fungal sinusitis typically occurs in immunocompromised patients. The authors report four cases of fungal sinusitis in immunocompetent young adults, all of whom had proptosis. METHODS: The diagnosis in all four patients was determined after orbital imaging and sinus biopsies. RESULTS: All four patients required surgical removal of the fungal source and anti-fungal chemotherapy postoperatively. CONCLUSION: Patients with proptosis, ocular pain, or other symptoms suggestive of orbital cellulitis unresponsive to antibiotic treatment should undergo radiographic imaging. If sinus disease is present, biopsy and culture may lead to the diagnosis of fungal disease. Surgical debridement and the appropriate systemic antifungal therapy usually lead to cure. PMID- 7777270 TI - Therapy of nonnecrotizing anterior scleritis with subconjunctival corticosteroid injection. AB - OBJECTIVE: To determine the safety and efficacy of subconjunctival triamcinolone (Kenalog) in treating nonnecrotizing anterior scleritis. DESIGN: The authors conducted a retrospective review of all patients treated with depot subconjunctival corticosteroid injection for scleritis from January 1988 to May 1993. Response to therapy was determined by subjective improvement in pain and a decrease in clinical signs of ocular inflammation. All patients received subconjunctival injections of triamcinolone by the same technique, and the minimum observation period for complications was 6 weeks. RESULTS: Eighteen patients (90%) had relief of their symptoms with clinically observable improvement in inflammation, whereas two patients (10%) responded poorly. Nine patients (45%) required no further therapy. Average symptom-free interval was 18 weeks in patients with recurrent scleritis. No complications of scleral thinning, perforation, or glaucoma occurred in any patients. CONCLUSION: Subconjunctival triamcinolone injection is highly efficacious in treating nonnecrotizing anterior scleritis without unreasonable risk of thinning and/or perforation and should be considered as adjunctive therapy in localized disease. PMID- 7777272 TI - Condensation on the posterior surface of silicone intraocular lenses during fluid air exchange. AB - PURPOSE: Posterior chamber foldable silicone intraocular lenses (IOLs) are becoming increasingly prevalent in patients undergoing a pars plana vitrectomy with fluid-air exchange. The authors report an important limitation of foldable silicone IOLs during fluid-air exchanges in pars plana vitrectomies. METHODS: The charts of 18 pseudophakic patients with foldable silicone IOLs who underwent vitrectomy with fluid-air exchange by the authors were reviewed. RESULTS: There was a statistically significant difference in the occurrence of condensation during fluid-air exchange between the group of patients with a capsulotomy versus those that did not have a capsulotomy (P = 0.003). Condensation limiting the view of the retina occurred during fluid-air exchange in 11 of 11 of the patients with foldable silicone lenses and a capsulotomy. Attempts to remove the condensation with a soft-tipped aspiration cannula resulted in limited view of the retina for 1 to 2 minutes in 6 of 11 patients. Use of a thin film of silicone oil restored the view in one patient. In the presence of an intact posterior capsule, condensation did not occur on identical foldable silicone IOLs in seven of seven patients. CONCLUSION: Recognition of the presence of a foldable silicone lens is important when an air-fluid exchange is anticipated. If a capsulotomy is present, the surgeon must be aware that condensation may limit the view of the retina severely during and after surgery. Intraoperatively, the view of the retina usually can be restored in short surgeries by wiping the posterior lens surface with a soft-tipped cannula, and in more complex surgeries by applying a thin film of silicone oil on the posterior surface of the lens. PMID- 7777271 TI - IgE, IgE receptors, and other immunocytochemical markers in atopic and nonatopic patients with vernal keratoconjunctivitis. AB - BACKGROUND: Vernal keratoconjunctivitis (VKC) often is associated with atopy but a considerable part of the patients lack evidence of specific hypersensitivity. An immunocytochemical study was undertaken with the aim of detecting possible differences in the tissue inflammatory response between atopic and nonatopic subjects with VKC. METHODS: Conjunctival biopsy specimens from six atopic and three nonatopic subjects with VKC (age range, 7-17 years) and eight healthy control subjects (age range, 3-15 years) were analyzed with a panel of monoclonal and polyclonal antibodies. RESULTS: No distinct differences in cell counts between atopic and nonatopic subjects with VKC were observed. Vernal keratoconjunctivitis specimens as a whole showed higher counts than control specimens for CD3+, CD4+, HLA-DR+, CD38+, EG2+, CD68+, IgE+, FC epsilon RI+, IgA+, IgG+, and IgM+ cells in the substantia propria; and for CD1a+, IgE+, and EG2+ cells in the epithelium. CONCLUSIONS: Because the number of cells expressing CD4, EG2, IgE, and the high-affinity receptor for IgE, all of which are considered relevant in infiltrates of allergic conditions, were similar in atopic and nonatopic subjects, the authors conclude that the role of allergen-specific IgE sensitization in the pathogenesis of VKC remains unclear. PMID- 7777273 TI - Bilateral bullous exudative retinal detachment complicating idiopathic central serous chorioretinopathy during systemic corticosteroid therapy. AB - PURPOSE: To present evidence that systemic corticosteroid therapy may cause bilateral bullous serofibrinous exudative retinal detachment in some patients with idiopathic central serous chorioretinopathy. BACKGROUND: Idiopathic central serous chorioretinopathy usually causes mild, transient loss of central vision, usually in otherwise healthy men with a type A personality. A few patients have permanent visual loss because of chronic and recurrent retinal detachment. The clinical findings in these patients may lead to incorrect diagnoses and use of corticosteroid therapy. METHODS: The clinical and photographic records of three patients in whom bilateral bullous serofibrinous exudative retinal detachment associated with idiopathic central serous chorioretinopathy developed after treatment with systemic corticosteroids were reviewed. RESULTS: Systemic corticosteroid treatment was instituted (1) as a prophylaxis to prevent exacerbation of the disease while undergoing surgery in the fellow eye, and (2) as the result of misdiagnoses of multifocal choroiditis and retinal vasculitis (Eales disease). Two of the patients had a history of chronic recurrent retinal detachments before institution of corticosteroid treatment. In one of these patients, bilateral chronic inferior retinal detachment developed, causing peripheral retinal vascular nonperfusion, retinal neovascularization, and vitreous hemorrhage. All three patients had severe permanent visual loss in one or both eyes. CONCLUSION: The findings in these patients provide further evidence that systemic corticosteroid treatment may cause severe exacerbation of retinal detachment and lasting visual loss in some patients with idiopathic central serous retinopathy. Recognition of the atypical presentations of this disorder is important to avoid incorrect diagnoses and treatment. PMID- 7777274 TI - Optical coherence tomography of macular holes. AB - PURPOSE: To assess the potential of a new diagnostic technique called optical coherence tomography (OCT) for diagnosing and monitoring macular holes. This technique is a novel noninvasive, noncontact imaging modality that produces high longitudinal resolution (10-micron) cross-sectional tomographs of ocular tissue. METHODS: Optical coherence tomography is analogous to ultrasound except that optical rather than acoustic reflectivity is measured. Cross-sectional tomographs of the retina profiling optical reflectivity in a thin, optical slice of tissue are obtained with a longitudinal resolution of 10 microns. Optical coherence tomography was used to examine 49 patients with the clinical diagnosis of idiopathic full-thickness macular hole, impending macular hole, epimacular membrane with macular pseudohole, or partial-thickness hole. The resulting OCTs were correlated with contact lens and slit-lamp biomicroscopy, fundus photography, and fluorescein angiography. RESULTS: The cross-sectional view produced by OCT was effective in distinguishing full-thickness macular holes from partial-thickness holes, macular pseudoholes, and cysts. Optical coherence tomography was successful in staging macular holes and provided a quantitative measure of hole diameter and the amount of surrounding macular edema. Optical coherence tomography also was used to evaluate the vitreoretinal interface in patients' fellow eyes and was able to detect small separations of the posterior hyaloid from the retina. CONCLUSION: Optical coherence tomography appears potentially useful as a new, noninvasive, diagnostic technique for visualizing and quantitatively characterizing macular holes and assessing fellow eyes of patients with a macular hole. The tomographic information provided by OCT eventually may lead to a better understanding of the pathogenesis of macular hole formation. PMID- 7777275 TI - Treatment of idiopathic macular holes by induced posterior vitreous detachment. AB - PURPOSE: To determine if an expansile gas bubble can relieve vitreofoveal traction without vitrectomy by inducing a posterior vitreous detachment (PVD) in eyes with an idiopathic impending or full-thickness macular hole (stages 1-3). The status of the impending and full-thickness macular holes after gas injection and tamponade also was studied secondarily. METHODS: Eighteen patients participated in this pilot study. Eleven patients with an impending macular hole (stages 1A and 1B) and seven patients (8 eyes) with a full-thickness macular hole (stages 2 and 3) received gas injections and prospectively were followed for an average of 15.6 months (range, 3-42 months). RESULTS: A complete PVD was achieved in 18 of 19 eyes without a prior PVD within 2 to 9 weeks after gas injection. Ten of the 11 impending holes (all 7 had stage 1A holes; 3 of 4 had stage 1B holes) resolved after gas injection. After gas tamponade, three of six early full thickness (stage 2) macular holes closed. None of the stage 3 macular holes closed after gas injection. The mean best-corrected visual acuity of the successful eyes was 20/32. There were no major complications. CONCLUSION: An expansile gas bubble consistently can induce a PVD in aging eyes. The ability of an expansile gas bubble to induce a PVD with minimal morbidity and expense may have clinical applications for macular hole therapy. Impending macular holes may resolve and some early full-thickness (stage 2) macular holes may close after gas injection and tamponade without vitrectomy. The efficacy and safety of this procedure may be evaluated further in the context of a carefully designed prospective and randomized study for selected patients with an idiopathic impending or early macular hole. PMID- 7777276 TI - Fundus photographic and fluorescein angiographic characteristics of pseudoholes of the macula in eyes with epiretinal membranes. AB - BACKGROUND: The fluorescein angiographic characteristics in eyes with pseudoholes of the macula associated with epiretinal membranes have not been studied extensively. METHODS: Stereo photographs and fluorescein angiograms from 83 consecutive eyes of 80 patients with pseudoholes of the macula were evaluated by two independent graders for epiretinal membrane opacity, fluorescence in the base of the pseudohole, and late perifoveal pooling of dye. RESULTS: Hyperfluorescence in synchrony with choroidal fluorescence appeared within the base of the pseudohole in 52 (63%) of the 83 eyes studied. The hyperfluorescence was smaller than the pseudohole in 37 (45%) eyes. Diffuse hyperfluorescence filled the pseudohole in 15 (18%) eyes. No fluorescence was seen in 20 (24%) eyes. Eleven (13%) eyes could not be graded due to coexistent macular disease or media opacity. Fluorescence within the area of pseudohole was less common in eyes with opaque epiretinal membranes than in eyes with visible or transparent epiretinal membranes (P = 0.002). Fluorescence within the area of the pseudohole was also less common in eyes with evidence of macular edema on fluorescein angiography (P < 0.001). The mean visual acuity was better for eyes with hyperfluorescence within the area of the pseudohole than for eyes without hyperfluorescence (P < 0.01). CONCLUSION: A common fluorescein angiographic characteristic associated with pseudoholes of the macula is early hyperfluorescence within the area of the pseudohole. This hyperfluorescence coincides with choroidal filling and appears to be a form of transmission defect rather than a blocking of surrounding choroidal fluorescence by the epiretinal membrane. This central hyperfluorescence may result in misdiagnosis of the macular pseudohole as a full-thickness macular hole. PMID- 7777277 TI - Posterior segment complications after vitrectomy for macular hole. AB - PURPOSE: The purpose of this study is to assess the rate of posterior segment complications after vitreous surgery for macular holes and to evaluate the effect of such complications on final visual outcome. METHODS: The authors reviewed retrospectively all cases of vitreous surgery for macular holes performed between June 1990 and October 1993. Among 98 patients with a followup of 3 months or more, all patients with posterior segment complications during the postoperative course were identified. The rate of complications was compared with that seen after vitreous surgery for macular pucker performed by the same surgeons. RESULTS: Posterior segment complications were noted in 23 (23%) of 98 patients. These included peripheral retinal breaks (3%), rhegmatogenous retinal detachment from a peripheral retinal break (14%), enlargement of the hole (2%), late reopening of the hole (2%), retinal pigment epithelium loss under the hole (1%), photic toxicity (1%), and endophthalmitis (1%). In 40% of these eyes, the final visual acuity was two lines or more below preoperative visual acuity. When compared with the macular pucker group, the rate of posterior segment complications, in particular the rate of peripheral retinal tears and detachments, was significantly higher (P < or = 0.05). CONCLUSIONS: The authors conclude that visually significant posterior segment complications may occur after vitrectomy for macular hole, and the rate of these complications appears to be higher than expected. PMID- 7777278 TI - Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study. AB - BACKGROUND: The pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains obscure. The placoid lesions and characteristic findings on fluorescein angiography have been interpreted as representing either primary disease of the retinal pigment epithelium or disease of the choroidal vasculature. This study used indocyanine green (ICG) choroidal videoangiography to investigate this controversy. METHODS: Sequential choroidal videoangiography was performed with ICG and a scanning laser ophthalmoscope on patients with acute posterior multifocal placoid pigment epitheliopathy. Image analysis was used to differentiate between masking and ischemia as to the cause of hypofluorescence on the angiograms. RESULTS: Indocyanine green angiograms of acute posterior multifocal placoid pigment epitheliopathy showed areas of hypofluorescence in both the early and late pictures that correlated with the placoid lesions. Image analysis identified these as areas of choroidal hypoperfusion. Successive films showed partial or complete resolution of these hypofluorescent areas. CONCLUSIONS: Indocyanine green choroidal videoangiography has shown choroidal hypoperfusion to underlie the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy. PMID- 7777279 TI - Quantitative assessment of the blue-light hazard during indirect ophthalmoscopy and the increase in the "safe" operating period achieved using a yellow lens. AB - PURPOSE: The indirect ophthalmoscope presents a blue-light hazard with the potential for causing photochemical injury to the retina. In this study, this hazard was assessed with respect to the threshold limit values (TLVs) recently adopted by the American Conference of Governmental Industrial Hygienists. METHOD: Spectral radiometric measurements were made from a standard indirect ophthalmoscope headset used in conjunction with either a clear or a yellow lens. The results were weighted spectrally with the published blue-light hazard function. RESULTS: When the clear lens was used, the TLV was exceeded after approximately 2.5 minutes. The yellow lens filtered out the more hazardous blue wavelengths of light and this increased the "safe" operating period by a factor of approximately 20. CONCLUSION: In clinical practice, with a clear lens, the TLV could be exceeded easily if the patient is subjected to prolonged or repeated examination because the blue-light hazard is additive in a linear manner for periods as long as 3 hours with a potential for a cumulative effect over longer periods. Furthermore, some ophthalmic patients, such as those with aphakia, are less tolerant of blue-light than healthy subjects. In the interests of patient safety, it is recommended that yellow lenses are considered for use for routine indirect ophthalmoscopy. PMID- 7777280 TI - Histopathology of bone spicule pigmentation in retinitis pigmentosa. AB - PURPOSE: To evaluate bone spicule pigmentation, a fundus feature in retinitis pigmentosa (RP) formed by migration of pigment-containing cells to perivascular sites in the inner retina. METHODS: The authors performed light and electron microscopy, including immunocytochemistry, on the retinas from ten patients with RP and five normal donors. RESULTS: The pigment-containing cells in regions of bone spicule pigmentation were derived from the retinal pigment epithelium (RPE). The translocated cells were remarkably polarized with a number of specializations characteristic of RPE cells in situ, but they did not contain lipofuscin granules and were not immunoreactive for cellular retinaldehyde-binding protein. The cells were linked by junctional complexes and formed epithelial layers around retinal vessels and next to the inner limiting membrane. Adjacent Muller cell processes contained glial fibrillary acidic protein-positive filaments and formed microvilli and intermediate junctions, resembling those in the external limiting membrane. Vascular endothelial cells adjacent to the translocated RPE cells were thin and fenestrated, resembling the choriocapillaris, and were separated from the pigmented cells by a layer of extracellular matrix similar in organization to Bruch membrane. Thickening of the matrix layer caused narrowing and occlusion of the vascular lumina. CONCLUSIONS: The lack of lipofuscin granules and cellular retinaldehyde-binding protein immunoreactivity in the translocated RPE cells is probably related to the loss of photoreceptors. The development of fenestrations in the endothelial cells correlates with the leakiness of retinal vessels to fluorescein observed in some cases of RP. Narrowing and occlusion of vascular lumina by thickening of the surrounding layer of extracellular matrix may contribute to the loss of inner retinal neurons found in RP. These changes in the RPE, blood vessels, glia, and inner neurons warrant consideration in designing therapies to restore vision to degenerate retinas. PMID- 7777281 TI - Predictors of outcome in patients who underwent cataract surgery. AB - PURPOSE: To identify preoperative patient characteristics associated with a lack of improvement on one or more measures 4 months after cataract surgery. METHODS: The authors collected preoperative and 4-month postoperative information on 552 patients undergoing first-eye cataract surgery from the practices of 72 ophthalmologists in three cities. The principal outcomes assessed were (1) Snellen visual acuity, (2) a cataract-related symptom score (possible range: 0, 0 of 6 symptoms present or bothersome, to 18, all 6 symptoms very bothersome), and (3) a measure of functional impairment in patients with cataract--the VF-14 score (possible range: 0, inability to perform any of the applicable activities, to 100, no difficulty performing any of the applicable activities). Multiple logistic regression was used to assess the association between preoperative patient characteristics and failure to improve on one or more outcome measures. Multiple linear regression was used to estimate the adjusted rate of lack of improvement in one or more outcome measures for one group of patients compared with another. RESULTS: Although 91 patients (16.5%) failed to improve on one or more of the outcome measures assessed, only 2 (0.4%) failed to improve on all three measures. The 91 patients who did not improve on at least one measure were approximately one sixth as likely to be satisfied with their vision postoperatively as the 461 patients who improved on all three outcome measures. Preoperative age of 75 years of age or older, VF-14 score of 90 or higher, cataract symptom score of 3 or lower, and ocular comorbidity (glaucoma, diabetic retinopathy, or age-related macular degeneration) were associated independently with increased likelihood of not improving on one or more measure (odds ratio: 3.57, 2.10, 3.29, and 2.16, respectively). The mean adjusted rate of failure to improve on at least one of the outcome measures ranged from 20.5% to 26.5% for patients with these preoperative characteristics compared with 8.8% to 13.8% for those patients without them. The preoperative level of Snellen visual acuity was not associated with the likelihood of not improving on one or more of the outcomes assessed. CONCLUSIONS: The authors conclude that specific preoperative characteristics (age, comorbidity, cataract symptom score, and VF-14 score) are independent predictors of patient outcome after cataract surgery. PMID- 7777283 TI - Growth of the internal and external eye in term and preterm infants. AB - BACKGROUND: Better knowledge of the growth patterns of the external and internal eyes of neonates would permit more accurate diagnosis of disorders that affect ocular size such as infantile glaucoma and microphthalmos. Such disorders preferentially may affect certain parts of the internal eye but not other parts. No previous study statistically has evaluated internal ocular growth in preterm newborns. METHODS: A-scan ultrasonography was applied directly to the corneas of 101 healthy preterm and term newborns to determine axial length, anterior chamber depth, lens thickness, and vitreous chamber depth. The growth of these structures was evaluated by correlation and regression analyses. RESULTS: At term, the mean measurements were axial length, 16.2 mm; anterior chamber depth, 2.0 mm; lens thickness, 3.8 mm; and vitreous chamber depth, 10.5 mm. Postconceptional age correlated to axial length (P < 0.001), anterior chamber depth (P = 0.032), and vitreous chamber depth (P < 0.001), but not to lens thickness (P = 0.48). By regression analysis, the eyes of males grew faster than those of females (P < 0.001) mainly due to the vitreous chamber. CONCLUSION: In the last trimester and first 2 postnatal months, lens thickness remains constant, while the anterior chamber and, especially, the vitreous chamber deepen. PMID- 7777282 TI - The ultrasonic localization of retrobulbar needles during retrobulbar block. AB - PURPOSE: The tips of retrobulbar needles were visualized during retrobulbar block using ultrasound. The purpose of this study is to see how often the needle tip was located 5 mm behind the hind surface of the globe. METHODS: Twenty-five patients ranging in age from 22 to 84 years were studied after written informed consent was obtained. An ultrasonic photograph was taken before needle placement, with the needle in the proper position, and after local anesthetic had been injected. RESULTS: In none of the 25 patients studied was the needle tip at the 5 mm mark behind the eye. Placement ranged from 0.2 to 3.3 mm behind the globe. In 14 to 25 placements, the needle shaft was seen actually to indent the globe. The optic nerve was seen to be at least 9 mm from the needle tip in 6 of 25 patients. CONCLUSION: This study demonstrates that retrobulbar needle tips are closer to the globe than thought previously. A false sense of security may occur when performing retrobulbar blocks using only anatomic landmarks. PMID- 7777284 TI - A novel antibiofilm technology for contact lens solutions. AB - PURPOSE: Nonsteroidal anti-inflammatory drugs, including sodium salicylate, inhibit extracellular bacterial biofilm production. The authors studied the effect of the addition of sodium salicylate on bacterial adherence and biofilm formation on contact lenses and cases and commonly used medical polymers. METHODS: The study was done in vitro with bacterial adherence and biofilm measured on lenses and cases that were exposed to saline contaminated with Staphylococcus epidermidis and Pseudomonas aeruginosa with and without 1 and 3 mm sodium salicylate. Bacterial adherence to contact lenses was quantitated by a vortex assay and by scanning electron microscopy. Biofilm formation on contact lens cases and other polymers was measured by an optical density assay and a radiolabeling assay. RESULTS: Inhibition of biofilm formation was demonstrated on plastic contact lens cases in a dose-related manner with 1 and 3 mm sodium salicylate. A dose-related decrease in bacterial adherence also was noted. Assays with contact lenses also demonstrated less adherence in the presence of sodium salicylate. Electron micrographs of the contact lens showed less biofilm, most noticeable with 3 mm salicylate. Other studies demonstrated decreased adherence of S. epidermidis to polyethylene and polystyrene. Sodium salicylate also decreased biofilm on plastic tissue culture wells, but sorbic acid paradoxically increased deposition. CONCLUSION: The authors found that the addition of low-dose sodium salicylate to saline decreased the adherence of S. epidermidis and P. aeruginosa to contact lenses and lens cases. Biofilm production also was decreased on the lens cases and on medical polymers used to make plastic cases. These studies suggest that sodium salicylate deserves additional study to determine its use in contact lens solutions. PMID- 7777285 TI - Three-dimensional high-frequency ultrasonic parameter imaging of anterior segment pathology. AB - PURPOSE: High-frequency ultrasound allows high-resolution imaging of anterior segment anatomy and pathology. Acoustic echo data, however, contain information relating to the microanatomic structure of the interrogated tissue which is not evident in B-mode images. The aim of this study is to develop imaging techniques to demonstrate and quantify the distribution of acoustic scattering properties in ocular tissues in three dimensions. METHODS: A tumor of the iris and a hyphema were scanned using a 50-MHz ultrasound probe mounted on a computer-controlled two axis positioning system. Scan data from sequential parallel planes were used to make three-dimensional reconstructions. Digital signal processing and a mathematical model of acoustic backscatter then were used to represent the effective size and acoustic concentration of scattering elements using a false color representation superimposed on B-mode images. RESULTS: Three-dimensional reconstructions improved appreciation of the size and extent of pathology and allowed computation of tissue volumes. Parameter images demonstrated distinctive differences between diffuse and organized blood and allowed quantification of tumor scattering properties. CONCLUSIONS: Three-dimensional imaging of the anterior segment with high-frequency ultrasound allows construction of perspective images, which adds to the already significant clinical use of individual high-resolution B-mode images. Acoustic backscatter properties determined by tissue microstructure can be computed from echo data and represented in false color in three-dimensional reconstructions. PMID- 7777286 TI - Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas. AB - PURPOSE: To study the relation between vascular patterns and the biologically aggressive behavior of ciliary body melanomas. METHODS: The authors compared the frequency distribution of vascular patterns by location for 234 uveal melanomas (54 tumors involving the ciliary body, and 180 without ciliary body involvement). Stepwise Cox regressions (for the endpoint of time-to-death due to melanoma), performed separately for melanomas with and without ciliary body involvement, included the following variables: size, vascular patterns, cell type, mean of the largest nucleoli, mitoses, tumor infiltrating lymphocytes, age, and sex. A separate Cox regression procedure included the variable of tumor location. Kaplan Meier survival curves were generated for time to melanoma death with ciliary body involvement and melanomas without ciliary body involvement for tumors containing or lacking vascular networks. RESULTS: These vascular patterns appear more often in the ciliary body than in the choroid: parallel vessels (P = 0.022), arcs (P = 0.003), and parallel with cross-linking, arcs with branching, and loops and networks (all P = 0.0001). Stepwise regression for tumors confined to the choroid indicated that the presence of networks was the most significant variable (P = 0.0001); stepwise regression for tumors with ciliary body involvement suggested that only one variable, networks, was significant (P = 0.0066). Kaplan-Meier survival estimates indicated that the survival of patients with tumors containing networks in the ciliary body was comparable to those containing networks in the choroid. CONCLUSION: Regardless of location, ciliary body or choroid, the presence of vascular networks shortens survival. The tumor location does not enter a stepwise Cox regression model when vascular patterns are included as variables. Therefore, the aggressive behavior of ciliary body melanomas appears to be related to the tendency for vascular networks to develop in this location. PMID- 7777287 TI - Clinical use for AC IOLs. PMID- 7777288 TI - Laser iridotomy. PMID- 7777289 TI - Laser iridotomy. PMID- 7777290 TI - Past precedents, present pressures, future problems: ophthalmology in 2001. PMID- 7777291 TI - Glaucoma after congenital cataract surgery. AB - OBJECTIVES: To study eyes that manifested glaucoma after congenital cataract surgery and to identify factors that might lead to better diagnosis and treatment of such glaucoma. DESIGN: A retrospective review of patients treated for glaucoma that developed after congenital cataract surgery. RESULTS: Sixty-four eyes of 38 patients were studied. Open-angle glaucoma was the more frequent type of glaucoma (51 eyes, 79.7%). Glaucoma was diagnosed a mean interval of 12.2 years after cataract surgery, but it could occur at any time from months to decades after the cataract surgery. Medications alone were successful in intraocular pressure control in 21 (63.6%) of 33 eyes, and additional surgical procedures resulted in successful intraocular pressure control in 11 of 14 eyes in which they were performed. CONCLUSION: The authors cannot predict in which eyes glaucoma will develop after surgery for congenital cataracts. Once detected, the glaucoma can be treated successfully in the majority of cases. Careful follow-up, including examinations with the patient sedated or anesthetized as needed, is required. PMID- 7777292 TI - Treatment of postfiltration bleb leaks with autologous blood. AB - BACKGROUND: Managing filtration surgery bleb leaks can be difficult as well as frustrating. Treatment options traditionally have included aqueous suppressants, patching, and bleb compression devices. Previously, if conservative management failed, surgical revision was considered. METHODS: Six patients with thin avascular blebs and discrete leaking holes (2 had had full-thickness procedures, 4 had had trabeculectomy with mitomycin C) underwent subconjunctival injection of approximately 1 ml of whole autologous blood. Injections were made just lateral and just medial to the domed cystic elevation of the blebs. RESULTS: Five of six eyes were leak-free by the second day after the procedure. No complications occurred. After 4 to 12 months of follow-up, four eyes are currently leak-free. In these eyes, intraocular pressure is between 8 and 12 mmHg. CONCLUSION: Subconjunctival peribleb injection of autologous blood may be a safe and helpful adjunct in treating selected postfiltration surgery bleb leaks. PMID- 7777293 TI - Confrontation visual field loss as a function of decibel sensitivity loss on automated static perimetry. Implications on the accuracy of confrontation visual field testing. AB - PURPOSE: To evaluate the accuracy of confrontation visual field testing with regard to the density of the visual field defect and its location in the peripheral visual field. METHODS: A prospective comparison of confrontation visual field testing with full-threshold Humphrey automated static perimetry C24 2 or C30-2 was conducted at a university eye center over a 3-month period. Seventy-two patients with a variety of neurologic and ophthalmologic conditions underwent confrontation visual field testing and automated perimetry as a part of their evaluation. One visual field from each patient was analyzed for this study. RESULTS: Confrontation visual field testing yielded an overall sensitivity for detecting an abnormal visual field (full-field analysis) of 63%, when sensitivity of confrontation testing rested on the detection of just one abnormal quadrant. The sensitivity of confrontation testing varied depending on the type of visual field loss present: 51% for arcuate scotomas, 67% for visual field constriction, 78% for altitudinal scotomas, and 90% for hemianopias. The sensitivity of detecting abnormal visual field quadrants, rather than the full-field analysis, was, however, poor at 38%. The sensitivity of confrontation testing was lower for superior quadrant defects and higher for inferior quadrant defects. The estimated probability of detecting an abnormal visual field quadrant occurring at a -26 decibel sensitivity loss from age-matched healthy patients for superior quadrant defects and a -19-decibel sensitivity loss for inferior quadrant defects was 50%. The increased sensitivity noted for visual field defects and for inferior quadrant defects appears to be related, in part, to the density of the visual field loss present. CONCLUSION: Confrontation visual field testing is relatively insensitive unless a moderate to dense defect is present, and as such is a poor screening test. However, when visual field defects are identified with confrontation visual field testing, the defects often are real as per the high specificity (97%) and high positive predictive value (96%). PMID- 7777294 TI - Elastosis of the lamina cribrosa in pseudoexfoliation syndrome with glaucoma. AB - BACKGROUND: Pseudoexfoliation syndrome is characterized by the presence of glycoprotein fibers in ocular and extraocular tissues, and often is associated with glaucoma. Pseudoexfoliation material may be associated closely with elastic microfibrillar-associated glycoprotein as well as elastin. METHODS: Four optic nerve heads of two patients with pseudoexfoliation syndrome and glaucoma were examined using electron microscopy and immunogold detection of elastin. Optic nerve heads from healthy age-matched individuals and patients with primary open angle glaucoma were used for comparisons. RESULTS: In all eyes with pseudoexfoliation and glaucoma, there was marked and widespread elastosis in the connective tissue of the lamina cribrosa. Elastotic fibers appeared as large and irregular aggregates of electron-dense material labeled with anti-elastin antibody. Abundant microfibrils were interspersed in the elastotic aggregates, whereas no typical pseudoexfoliation fibers were observed. In contrast, there were less elastotic fibers in the lamina cribrosa from patients with primary open angle glaucoma compared with pseudoexfoliation glaucoma. Other changes of extracellular matrix were similar to those observed in primary open-angle glaucoma: decreases in collagen fiber density, presence of basement membranes not associated with cell surfaces, and abundant bundles of microfibrils not labeled with elastin antibody. The elastic fibers appeared normal in other locations within the optic nerves of patients with pseudoexfoliation glaucoma, including in the pial septa and blood vessels of the retrolaminar myelinated optic nerve. CONCLUSION: The authors' findings demonstrate marked and site-specific elastosis in the lamina cribrosa of patients with pseudoexfoliation syndrome with glaucoma, suggesting an abnormal regulation of elastin synthesis and/or degradation in the optic nerve of patients with this disease. PMID- 7777295 TI - 5-Fluorouracil filtering surgery and neovascular glaucoma. Long-term follow-up of the original pilot study. AB - BACKGROUND: The long-term efficacy and safety of filtering surgery with 5 fluorouracil (5-FU) in eyes with neovascular glaucoma are unknown. METHODS: Kaplan-Meier survival curve analysis of surgical outcome was performed on all 34 patients (34 eyes) enrolled from May 1982 through April 1986 in the original pilot study of filtering surgery with 5-FU. RESULTS: Success rates at the 1-, 2-, 3-, 4-, and 5-year intervals were 71%, 67%, 61%, 41%, and 28%, respectively. The median filter survival time was 38.7 months (95% confidence interval: 32-45 months). Twelve (35%) of 34 patients lost light perception vision, and phthisis bulbi developed in 8 (24%) of 34 patients. Age of 50 years or younger (P < 0.0001) and type 1 diabetes (P = 0.0004) were significant risk factors for surgical failure. The 1-year success rate for patients no older than 50 years of age was 23% compared with a 95% success rate in patients older than 50 years of age. After adjustment for age, type 1 diabetes was a borderline risk factor (P = 0.06). CONCLUSION: There is a high risk of long-term failure of filtering surgery with 5-FU in neovascular glaucoma. Patients 50 years of age or younger have an extremely poor prognosis. Patients older than 50 years of age have initial short term success with an accelerated failure rate after 3 years. PMID- 7777296 TI - In vitro and in vivo flow characteristics of glaucoma drainage implants. AB - PURPOSE: To determine pressure-flow characteristics at physiologic flow rates in vitro and in vivo in rabbits for Ahmed, Baerveldt, Krupin disk, and OptiMed glaucoma implants. The Molteno dual-chamber implant also was evaluated in vivo only. METHODS: Five samples of each glaucoma implant were studied. Baerveldt implants were ligated partially for in vitro testing. Opening and closing pressures in air or after immersion in balanced salt solution or plasma were evaluated for the valved devices (Ahmed and Krupin). Pressures were measured in vitro and in vivo in normal rabbits at flow rates preset at between 2 and 25 microliters/minute after the tubes were connected to a closed manometric system. In vivo measurements were made 24 hours after implantation. Resistance to flow was calculated using Poiseuille's equation after at least three separate flow rate readings. RESULTS: In air, the Ahmed and Krupin valves had opening pressures of 9.2 +/- 3.4 and 7.2 +/- 0.6 mmHg and closing pressures of 5.2 +/- 0.9 and 3.9 +/- 1 mmHg, respectively. Neither opening nor closing pressures could be determined when Ahmed and Krupin valves were immersed. In vitro, the Ahmed and OptiMed devices had higher pressures than did other devices at a 2 microliters/minute flow rate of balanced salt solution. During perfusion with plasma, only the OptiMed device maintained higher pressures than with balanced salt. With all devices, pressures fell rapidly to zero after flow was stopped. The OptiMed device demonstrated the highest resistance values. In vivo, the Ahmed device provided pressures of 7.5 +/- 0.8 mmHg and the OptiMed device gave pressures of 19.6 +/- 5.6 mmHg at a 2-microliters/minute flow rate. After 15 minutes of flow shutdown, the OptiMed implant maintained pressures of 7.1 +/- 1.1 mmHg. The Baerveldt (nonligatured), Krupin, and Molteno dual-chamber implants had similar resistances and pressures in vivo. Pressures with all devices in vivo fell rapidly to zero after conjunctival wound disruption. CONCLUSION: Neither the Ahmed nor Krupin devices had demonstrable opening or closing pressures when tested in vitro immersed in balanced salt solution or plasma. With all devices, pressures were higher in vivo than in vitro due to tissue-induced resistance around the explant. Both Ahmed and Krupin valves functioned as flow-restricting devices at the flow rates studied, but did not close after initial perfusion with fluid. PMID- 7777297 TI - Visual loss after neurosurgical repair of paraclinoid aneurysms. AB - OBJECTIVE: To describe three cases of unexplained visual loss after technically successful clipping of paraclinoid aneurysms. DESIGN: Three case reports are presented. RESULTS: Profound blindness occurred in all three patients. Only one patient had marked visual recovery. Two clinical patterns were observed. A fulminant orbital syndrome presumably from compromise of large draining veins of the orbit was observed in one patient. A retrobulbar optic neuropathy that might have resulted from either direct injury or damage to small dural vessels of the posterior optic nerve was observed in the other two patients. CONCLUSIONS: There is a risk of postoperative blindness after clipping of paraclinoid aneurysms. The frequency of this complication may increase because attempts to repair these aneurysms are becoming more common. Patients with paraclinoid aneurysms should receive preoperative and postoperative neuro-ophthalmologic examinations. PMID- 7777298 TI - The attenuation of blue-on-yellow perimetry by the macular pigment. AB - PURPOSE: To determine the influence of macular pigment absorption on blue-on yellow perimetry using a technique suitable for application with the Humphrey Field Analyzer. METHODS: The sample comprised one eye from each of 46 healthy subjects (age range, 20-80 years). Macular pigment absorption was assessed by measuring medium-wavelength sensitive cone sensitivity for 460- and 570-nm narrowband stimuli at the fovea, at 5.5 degrees and at 8 degrees eccentricity. The differences in sensitivities recorded between the fovea and 8 degrees eccentricity and between 5.5 degrees and 8 degrees eccentricity for the 460-nm stimulus relative to a value of zero at 570 nm were attributed to absorption by the macular pigment. Blue-on-yellow perimetry was undertaken using a 460-nm narrowband blue Goldmann size V stimulus and a yellow 330-cdm-2 background. RESULTS: Group macular pigment absorption (mean +/- standard error) was 0.40 +/- 0.03 log units foveally and 0.00 +/- 0.03 log units at 5.5 degrees eccentricity. The group mean foveal macular pigment absorption was significantly different from zero (P < 0.01). The coefficient of repeatability for the macular pigment absorption procedure (based on test-retest data for 16 subjects) was +/- 0.28 log units at the fovea and +/- 0.35 log units at 5.5 degrees eccentricity. CONCLUSION: The net effect of ocular media and macular pigment absorption relative to 460 nm was to attenuate the blue-on-yellow visual field at the fovea by approximately 0.80 log units and elsewhere by 0.40 log units. PMID- 7777299 TI - Ciliary body neurilemoma. Unusual clinical findings intimating the diagnosis. AB - BACKGROUND: Neurilemomas (schwannomas) rarely occur intraocularly. When present, they pose a diagnostic dilemma for the physician and often are mistaken as a malignant lesion, resulting in enucleation. METHODS: The authors report the clinical findings of a 46-year-old man with a slowly progressive growing mass of the anterior chamber, associated with glaucoma and the development of cataract. To further delineate the tumor's features, ancillary techniques, including ultrasonography, computed tomography, and magnetic resonance imaging, were conducted. A definitive anterior chamber biopsy of the tumor was performed with histologic examination and electron microscopy. RESULTS: Ultrasonography, high resolution computed tomography and magnetic resonance imaging showed a well delineated mass of the inferior ciliary body involving nearly 5 clock hours of the angle. Two clinical features that suggested a longstanding tumor were brilliant transillumination of the mass (leading to the impression of a "cystic mass," not corroborated by ultrasonography) and retrodisplacement of the involved iris root. The histology, and particularly the electron microscopic features, confirmed the diagnosis of a neurilemoma, a benign tumor of the anterior segment. CONCLUSION: Intraocular neurilemomas are extremely rare tumors. Few are well documented with modern ancillary techniques. Clinical findings in conjunction with radiographic and ultrasonic features may support the diagnosis of a benign tumor. For this patient, confirmation via biopsy permitted combined cataract and glaucoma surgery to rehabilitate the eye, which retains 20/20 visual acuity 3 years after the procedure. PMID- 7777300 TI - Acquired ptosis in the young and middle-aged adult population. AB - PURPOSE: The authors studied the etiology of acquired ptosis in the young to middle-aged adult population with specific attention to the role of rigid contact lens use. METHODS: The study consisted of all patients between the ages of 15 and 50 years with acquired ptosis who presented between April 1986 and May 1994. Potential factors responsible for acquired ptosis were investigated in all patients with specific attention directed to history and duration of contact lens wear. RESULTS: In the consecutive series of 91 young to middle-aged adults with acquired ptosis, we found contact lens wear to be the only identifiable cause in 47% of patients. This was the most common cause for acquired ptosis in this age group. Trauma was a distant second cause, accounting for 19% of patients. Of the contact lens-induced ptosis, 58% were unilateral and 42% were bilateral. Of the 25 patients who wore contact lenses and had unilateral ptosis on examination, manual elevation of the ptotic lid showed an unsuspected contralateral ptosis to be manifest in seven patients due to Hering's law. Ptosis was overwhelmingly associated with rigid contact lens wear, and levator aponeurosis disinsertion was found in the large majority at the time of surgical repair. CONCLUSION: This study suggests that contact lens-induced ptosis is a much more common cause of acquired ptosis in young and middle-aged adults than has been suspected previously. The ptosis is primarily due to levator aponeurotic disinsertion, presumably due to recurrent traction on the aponeurosis during rigid contact lens removal. PMID- 7777301 TI - Pneumatic retinopexy failures. Cause, prevention, timing, and management. AB - BACKGROUND: Pneumatic retinopexy is a procedure for reattaching the retina by injecting an expanding gas bubble and using either laser or cryopexy. The procedure is controversial because there may be a lower initial success rate, and intraocular gas may increase the risk of proliferative vitreoretinopathy. METHODS: The authors performed a retrospective review of 107 unpublished consecutive cases of pneumatic retinopexy together with a literature review of 25 statistical series with primary attention to failures. Univariate and multivariate analyses were carried out on the data set, and adjusted odds ratios for risk factors associated with failure were calculated using logistic regression. RESULTS: Initially, 74 (69%) of 107 patients had successful results, and with re-operations the success rate increased to 98%. Failure of the procedure to achieve retinal reattachment occurred soon after the initial procedure, with 86% of recorded failures occurring within the first month. The initial cause of failure was new or missed breaks in 14.9%, reopened initial breaks in 11.2%, and breaks never closed in 4.6%. Risk factors that showed a correlation with failure were patients being male (adjusted odds ratio = 2.65), eyes with preoperative visual acuity worse than 20/50 (adjusted odds ratio = 1.21), eyes with four quadrants of retinal detachment or total detachment (adjusted odds ratio = 2.03), aphakic or pseudophakic eyes (adjusted odds ratio = 1.91), and eyes with additional pathologic findings (adjusted odds ratio = 3.14). Poor visual outcome was associated with initial visual acuity less than 20/50 (adjusted odds ratio = 15.7) and eyes with four quadrants of retinal detachment or total detachment (adjusted odds ratio = 5.01). CONCLUSIONS: Failures of pneumatic retinopexy occur early in the postoperative course. Factors known to be associated with failure of retinal reattachment using scleral buckling also were associated with failure in pneumatic retinopexy. A higher success rate in females was noted, suggesting that educational efforts may need to be greater in males. Poorer visual results occurred in patients with poor initial vision and in eyes with four quadrants of retinal detachment or total detachments. PMID- 7777302 TI - Macular changes in pseudotumor cerebri before and after optic nerve sheath fenestration. AB - PURPOSES: Macular abnormalities such as chorioretinal striae, pigmentary disturbances, exudates, and subretinal hemorrhage or scar can occur in patients with pseudotumor cerebri. The purpose of this study is to determine the potential resolution of the macular abnormalities after optic nerve sheath fenestration, as well as the visual significance of these changes. METHODS: The authors retrospectively compared the preoperative and postoperative examinations of seven patients with pseudotumor cerebri-associated macular changes who underwent unilateral optic nerve sheath fenestration. RESULTS: Preoperatively, visual acuity was worse than 20/25 in two patients with macular exudates and in one with a subretinal scar. Chorioretinal striae and pigment mottling did not appear to decrease visual acuity. With a mean postoperative follow-up of 14 months, the patients with exudates had improvement in visual acuity and clearing of the exudates, unlike the patient with the subretinal scar. Chorioretinal striae, pigment mottling, and the subretinal scar did not resolve with surgery. CONCLUSIONS: This study suggests that chorioretinal striae and pigment mottling in the setting of pseudotumor cerebri, unlike exudates and subretinal scars, do not have a significant effect on visual acuity. After optic nerve sheath fenestration, only macular exudates decreased. Therefore, the persistence of striae, pigment mottling, and macular scars, in the face of resolved papilledema and improved visual fields, does not indicate failure of the optic nerve sheath fenestration. PMID- 7777304 TI - Penetrating keratoplasty after radial keratotomy. A report of six patients. AB - BACKGROUND: For more than 15 years, radial keratotomy has increased in popularity as an option for treating myopia in the United States. During this period of time, the procedure has been modified to improve results and decrease complications. Despite these changes, complications from radial keratotomy continue to occur. The authors report six cases of penetrating keratoplasty performed to correct significant loss of vision resulting from complications of radial keratotomy. METHODS: The surgical records of one author (WR) were reviewed retrospectively for penetrating keratoplasties performed for complications of radial keratotomy. RESULTS: Six cases of penetrating keratoplasty performed for complications of radial keratotomy were found. Severe loss of vision was the indication for surgery in each case, and was associated with aggressive and repeated incisional refractive attempts to correct astigmatism, hyperopic overcorrection, residual myopia, or refractive errors associated with keratoconus. Glare associated with subepithelial scarring and irregular astigmatism were the primary findings associated with loss of vision. CONCLUSIONS: Despite advances in technique and instrumentation, radial keratotomy is limited in the amount of myopia it can correct. The risk for loss of vision increases with increasing number of incisions, intersecting incisions, very small optical zones, and keratoconus. PMID- 7777303 TI - Vortex vein exit sites. Scleral coordinates. AB - PURPOSE: The authors determined the frequency and scleral coordinates of vortex vein exit sites in 46 autopsy eyes to provide topographic data that will enable surgeons to locate these vessels more precisely. METHODS: Forty-six autopsy eyes were examined under a dissecting microscope to measure the frequency of vortex veins and the cord lengths between the vortex vein scleral exit sites and the limbus, rectus muscle insertions, and oblique muscle insertions. RESULTS: Data from this study showed that 32 (70%) of the 46 individual eyes studied had more than four vortex veins. The number of second or third vortex veins found in the nasal quadrants was significantly higher than the number found in the temporal quadrants (P < 0.01). Statistical analyses of the measurements provided mean values for distances between vortex vein scleral exit sites and the three nearest extraocular muscle insertions; these positions among eyes were found to be relatively uniform (standard deviation, 0.7-2.5 mm). CONCLUSION: The authors suggest that the majority of adult eyes encountered by a surgeon will have more than four vortex vein exit sites and that more vortex veins may be expected in the nasal quadrants than in the temporal quadrants. This study delineates the locations of vortex vein exit sites so that surgeons can reliably predict their surface positions to avoid vessel laceration and its ensuing complications. PMID- 7777305 TI - Corneal topography of phase III excimer laser photorefractive keratectomy. Optical zone centration analysis. Summit Photorefractive Keratectomy Topography Study Group. AB - PURPOSE: To determine the amount of optical zone decentration in patients who have undergone excimer laser photorefractive keratectomy (PRK) and assess associations of both decentration and optical zone size with clinical outcomes. METHODS: Optical zone centration in 185 patients after PRK was analyzed using computer-assisted videokeratography. A comparison of decentration among the five study centers was performed. Associations of clinical outcomes with procedure decentration and optical zone size were assessed. RESULTS: Decentration from the pupil center ranged from 0.00 to 1.44 mm (mean, 0.46 mm): 21.8% were decentered 0.25 mm or less, 42.5% > 0.25 mm and < or = 0.50 mm, and 97.1% < or = 1.00 mm. In both eyes, the average decentration from the pupil center was located inferonasally. Decentrations among the five study centers were significantly different. Decentration was associated with attempted refractive correction, change in keratometric cylinder, and patient satisfaction. There was a trend toward worse postoperative uncorrected visual acuity with greater decentration but no association with best-corrected vision, predictability, or refractive astigmatism. No significant relation was found between decentration and glare/halo ranking; however, three of six patients with 1.00 mm or greater of decentration demonstrated a high glare/halo grade. Although optical zone size was not associated with glare or halo, subjective patient satisfaction was greater with a 5.0-mm optical zone than with a 4.5-mm optical zone. CONCLUSIONS: Centration is an important surgeon-controlled variable in excimer laser PRK. Decentration of excimer laser refractive procedures was found to be nonrandom and may be influenced by preoperative pupil management. Moreover, the amount of decentration may influence clinical outcomes. Improved techniques and centering procedures on nonmiotic pupils may improve future results. PMID- 7777306 TI - Corneal topography of phase III excimer laser photorefractive keratectomy. Characterization and clinical effects. Summit Photorefractive Keratectomy Topography Study Group. AB - PURPOSE: To define qualitative patterns of corneal topography after excimer laser photorefractive keratectomy (PRK), assess changes in patterns, associations with clinical outcomes, and the accuracy of videokeratography in predicting results, and define quantitatively the optical zone contour. METHODS: Computer-assisted videokeratography data obtained from 181 patients after PRK was analyzed. Topography patterns at two time points were characterized, and associations with clinical outcomes were tested. Power change predicted by topography was compared with refractive change, and cross-sectional power contours were analyzed. RESULTS: Seven topography patterns were defined. At 1 year, 58.6% of corneas showed a homogeneous topography, 17.7% showed a toric-with-axis configuration, 2.8% showed a toric-against-axis configuration, 13.8% showed an irregularly irregular topography, 2.8% showed a keyhole/semicircular pattern, and 4.4% showed focal topographic variants. No central island patterns were found. Of the maps, 41% changed over time. Uncorrected vision, predictability, and patient satisfaction were best in the homogeneous group. Astigmatism increased in the irregular and toric-against-axis groups and decreased in the toric-with-axis group. There was no relation of topography pattern to best-corrected vision or subjective glare/halo. Cross-sectional power profiles showed a homogeneous power change for the central 3 mm with a diminution in correction toward the periphery. The topography unit tended to overestimate refractive change for corrections of 5 diopters or less and underestimate the change for corrections greater than 5 diopters. CONCLUSIONS: Topography patterns after PRK are identifiable, time dependent, and may affect clinical outcomes. Understanding the actual corneal optical contour resulting from PRK may aid in improving both laser techniques and optical results in the future. PMID- 7777309 TI - Rabies in Southern and Eastern Africa. Proceedings of a workshop. Onderstepoort, South Africa, 3-5 May 1993. PMID- 7777308 TI - Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis. AB - BACKGROUND: Shield-shaped corneal ulcers and plaques are serious sight threatening corneal manifestations of vernal keratoconjunctivitis. There are few reports describing the management of these patients and their outcomes. METHODS: The clinical presentation, treatment, and outcome of 66 shield ulcers and/or plaques in 55 eyes of 41 patients with vernal keratoconjunctivitis were studied in this retrospective study of patients treated at King Khaled Eye Specialist Hospital during an 11-year period. RESULTS: Patients with shield ulcers where the base of the ulcer was transparent usually had rapid re-epithelialization and an excellent visual outcome with medical treatment alone. Patients with shield ulcers and visible plaque formation had delayed re-epithelialization when receiving only medical treatment. Complications of delayed re-epithelialization consisted of bacterial keratitis in five eyes, amblyopia in one eye, and strabismus in one patient. CONCLUSIONS: Patients with shield ulcers and/or plaques that do not re-epithelialize once active vernal keratoconjunctivitis has been controlled should have surgical intervention. In this series, a simple scraping of the base and margins of the ulcer with removal of the inflammatory material (i.e., the plaque) resulted in rapid re-epithelialization in 20 of 23 ulcers and plaques. An algorithm for treating shield ulcers and/or plaques is presented based on the experience at this institution. PMID- 7777307 TI - Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti inflammatory drug in treating traumatic corneal abrasions. AB - BACKGROUND: Treating traumatic corneal abrasions is a common problem for the ophthalmologist. Traditional management has been the use of a pressure patch. Three different therapeutic modalities were evaluated for their efficacy in treating traumatic corneal abrasions. METHODS: Forty-seven consecutive patients with traumatic corneal abrasions were randomized prospectively in a single masked, controlled clinical trial which compared the efficacy of (1) pressure patching, (2) a bandage contact lens, and (3) a bandage contact lens with a topical nonsteroidal anti-inflammatory drug (0.5% ketorolac tromethamine). RESULTS: There was no significant difference in the healing time of the three groups. However, psychometric analysis showed a significant decrease in pain in the group that received a bandage contact lens with a topical nonsteroidal anti inflammatory drug. There was a significant difference in the ability to return to normal activities in both contact lens groups compared with the pressure-patch group. There was no significant difference among the three groups with respect to photophobia, redness, ocular irritation, headache, or tearing. CONCLUSION: Use of a bandage contact lens significantly shortens the time required for a patient to return to normal activities. Moreover, addition of a nonsteroidal anti inflammatory drug to a treatment regimen significantly decreases the pain associated with traumatic corneal abrasions. Use of a bandage contact lens with a topical nonsteroidal anti-inflammatory may prove to be an effective adjunct in treating traumatic corneal abrasions. PMID- 7777310 TI - The rabies virus genome: an overview. AB - The replication strategy, genome organization and extent of variation within the genome of the genus Lyssavirus is briefly reviewed. Strategies used in the approach to genome studies are discussed. PMID- 7777311 TI - Taxonomy and evolutionary studies on lyssaviruses with special reference to Africa. AB - Currently, the Lyssavirus genus is composed of four serotypes and the ungrouped European bat lyssaviruses (EBL). Using previously described PCR amplification and direct sequencing methods, the N genes of 70 representative lyssaviruses collected from 40 different countries were examined. From the results, a phylogenetic tree with six branches (genotypes) was constructed: genotypes 1-4 correlated with the classification of serotypes 1-4 and in addition EBL 1 and EBL 2 were identified as two further genotypes (5 and 6). Analysis of the 51 rabies (genotype 1) viruses in the study identified nine distinct groups which could be correlated with their geographical origins. A comparison of the six genotypes with four principal Vesiculovirus serotypes showed that their relationship was closer than that of even the two most closely related Vesiculovirus serotypes. Antigenic site sequences of isolates from vaccine/treatment failures were similar to vaccine and field strains, suggesting that failures were not due to genetic variation at the N protein level. PMID- 7777314 TI - Canid and viverrid rabies viruses in South Africa. AB - Historical records suggest that in South Africa rabies was present in viverrids in the early 1800s. In the early 1950s a wave of canine rabies spread from Namibia through Botswana into the northern Transvaal and by 1961 a second front had penetrated south from Mozambique into Swaziland and northern Natal. Today, rabies is regularly confirmed in a number of canid and viverrid species in most regions of South Africa. A panel of anti-nucleoprotein monoclonal antibodies was used to examine 83 virus isolates from these species. Two major reaction patterns, one chiefly confined to viruses from canids and the other to viruses from viverrids, were obtained. In addition, some variation in the reaction patterns of viverrid viruses was observed and spill-over of viverrid virus into canids and vice versa was recorded. Rabies in South Africa appears to behave as two distinct disease entities. PMID- 7777313 TI - Molecular analysis of rabies-related viruses from Ethiopia. AB - From brain samples collected from domestic animals in Ethiopia, two rabies related viruses were isolated. According to their reactivity pattern with anti nucleocapsid monoclonal antibodies, they were characterized as Lagos bat virus (isolate Eth-58) and Mokola virus (isolate Eth-16). This classification was confirmed by neutralization experiments with Mokola and Lagos bat specific antisera. Two potent anti-rabies vaccines were unable to protect mice against the two rabies-related viruses. In order to investigate molecular relationships to classical rabies virus, cDNA cloning and sequencing was performed. The RNA genome of both viruses comprises 12 kilobases (kb) and has an organization similar to that of rabies virus with the gene order 3'-N-P-M-G-L-5'. Using virus-specific cDNA as probes in heterologous hybridization experiments, the RNAs of other members of lyssavirus serotypes 2 and 3 were detected. From hybridization experiments and sequence analysis of the 3' terminal 5,5 kb of the genomes, Eth 16 and Eth-58 viruses were shown to be equally genetically distant from rabies virus with 60% nucleotide identity; Eth-16 and Eth-58 had 68% homology. PMID- 7777312 TI - Monoclonal antibody studies on rabies-related viruses. AB - Rabies and rabies-related viruses are divided into four serotypes, although it has been suggested that the inclusion of European bat lyssaviruses results in six genotypes. Sixty-four rabies-related viruses were tested against a panel of 36 anti-nucleocapsid monoclonal antibodies prepared from the immunization of Balb/c mice with five prototypic rabies-related viruses. Reaction patterns obtained confirmed the original distinction between serotype 1-4 viruses and revealed multiple variants of Lagos bat and Mokola viruses. In addition, two biotypes of European bat lyssavirus were identified and a clear distinction was shown between these biotypes and Duvenhage virus of Africa. The origins and importance of the rabies-related viruses are discussed. PMID- 7777315 TI - Molecular epidemiology of rabies virus in South Africa. AB - Nucleic acid sequence analysis was used to determine the phylogenetic relationships amongst rabies viruses isolated from typical canid hosts such as bat-eared fox, jackal and dog in South Africa (SA). Geographical factors were taken into account in the selection of isolates and three different regions within the genomes of the isolates were compared for their use as phylogenetic indicators. The three genome regions, being the cytoplasmic domain of the G-gene, the G-L intergenic pseudogene and the antigenic domain II of the N-gene were found to differ in terms of the of nucleic acid conservation, but produced similar results when analyzed phylogenetically. The SA canid isolates were found to be closely related and could clearly be distinguished from all other rabies virus groups for which sequence data is available. In addition four SA mongoose rabies isolates were studied which were shown to be distant from the SA canid rabies virus group as well as from any other rabies viruses (or group) for which sequence data is available. Our results also indicate that spillover between the distinct canid and viverrid host reservoirs may occur. PMID- 7777316 TI - Rabies in wild and domestic carnivores of Africa: epidemiological and historical associations determined by limited sequence analysis. AB - Virus isolates from three important reservoirs for rabies in Africa (domestic dogs, jackals and yellow mongooses) were compared by their reaction with a panel of monoclonal antibodies directed to the nucleocapsid protein and by the nucleotide sequence of a 200 base pair segment of the nucleocapsid gene. Although antigenically dissimilar, the variants commonly transmitted in dogs and jackals were very closely related by genetic analysis. Phylogenetic analysis and historical accounts support a common lineage for these variants in both past and present reservoirs for rabies in Europe. Two additional variants, distinct from the dog or jackal variant, were found in yellow mongoose samples and nucleotide sequence from these animals showed more divergence than any other group of samples. These variants and a third variant for which no host species could be identified, were shown to form two additional genetic groups only distantly related to each other. These three variants and a previously identified variant in Nigeria may be indigenous to African carnivores. PMID- 7777317 TI - Rabies in southern Africa. AB - The first confirmed outbreak of rabies in Africa, believed to have followed the importation of an infected dog from England in 1892, occurred in the eastern Cape Province of South Africa, and was brought under control in 1894. An unconfirmed epidemic of rabies in dogs occurred in western Zambia in 1901. By the following year the disease had apparently spread along a major trade route, to cause an outbreak in Zimbabwe which engulfed most of the country before being eradicated in 1913. The existence of endemic rabies of viverrids (mongooses and genets) was confirmed in South Africa in 1928, and since then the viverrid disease has continued to occur widely on the interior plateau of the country with spill-over of infection to cattle and a variety of other animals. From about 1947 onwards, an invasive form of dog rabies spread from southern Zambia and/or Angola into Namibia, across northern and eastern Botswana into Zimbabwe and the northern Transvaal by 1950, entered Mozambique in 1952, and spread from there to Swaziland in 1954. Dog rabies extended from southern Mozambique into Natal in 1961 to cause a major epidemic which was brought under control in 1968. The disease re-entered northern Natal from Mozambique in 1976 and since then dog rabies has proved difficult to control in the peri-urban settlements of Natal-KwaZulu. The disease spread from Natal to Lesotho in 1982, and into the Transkei region of the eastern Cape Province in 1987, to reach the Ciskei by 1990. The spread of the disease in dogs was followed by the emergence of rabies of jackals and cattle in central Namibia, northern Botswana, Zimbabwe and the northern Transvaal. A unique outbreak of rabies in kudu antelope occurred in central Namibia from 1977 to 1985, apparently involving oral spread of infection between individuals. A few cases of rabies in the bat-eared fox were recognized each year in Namibia from 1967 onwards, and from the 1970s the occurrence of the disease in the fox has emerged as a distinct problem in the northern Cape Province and spread to the west coast. The rabies-related viruses, Lagos bat, Mokola and Duvenhage, associated with bats, shrews and rodents in Africa, are known to have caused isolated cases of disease in South Africa, and on one occasion a small outbreak involving six cats and a dog in Bulawayo, Zimbabwe.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777319 TI - Rabies and wildlife: a conservation problem? AB - Understanding the behavioural ecology of wild mammals in rabies epizootics is a prerequisite to scientifically sound management of the disease. The principal vectors of wildlife rabies in a region tend to be abundant representatives of the Carnivora. Although the population dynamics of these species may be radically affected by rabies, and by attempts to control it, they are generally not threatened with widespread extinction as a result. However, the cases of the Blanford's fox, Vulpes cana, the Ethiopian wolf, Canis simensis, and the African wild dog, Lycaon pictus, illustrate how rabies and its control can pose grave conservation problems for rare carnivores. Disease monitoring is therefore an important element of recovery plans for rare species which are potential victims of rabies and other epizootic pathogens, and the benefits and disbenefits of prophylactic vaccination merit serious evaluation. PMID- 7777320 TI - Current status of fox rabies in Europe. AB - There was a general decline in animal rabies in Europe in 1991 following the peak levels which occurred in 1989. This was ascribed, in France at least, to the normal decline in cases usually experienced following peak occurrence and also to oral immunization of foxes against rabies. European countries in which rabies occurs may be infected by fox, insectivorous bat or dog rabies. This paper makes a general summary of the rabies situation in Europe in 1991 and presents data obtained in 1991 from 15 European countries using oral vaccination against fox rabies. PMID- 7777318 TI - Wildlife rabies in perspective. AB - Populations of a number of species of the orders Carnivora and Chiroptera maintain independent rabies epidemics in different parts of the world. However, in large parts of Africa, Asia, and Latin America, rabid dogs outnumber diagnosed wildlife cases. Rabies virus variants circulating in different host populations can be distinguished by the use of monoclonal antibodies and by genomic analysis. Rabies virus strains and their hosts have to be co-adapted in order to allow their prolonged co-existence. PMID- 7777321 TI - Jackal rabies in Zimbabwe. PMID- 7777322 TI - Biology of the black-backed jackal Canis mesomelas with reference to rabies. AB - The black-backed jackal is represented in rabies records from southern Africa and is suspected of playing an important role in the disease in this region. The basic biology of the species suggests that it does have certain characteristics that could make it an ideal rabies vector. However, the engimatically low incidence of rabies in undisturbed jackal populations suggests that more subtle processes may be involved. It is suggested that jackal society is arranged in the form of cryptic packs and that disruption of the hierachy through persecution may increase agonistic encounters and thence the incidence of rabies. Suggestions are made for the incorporation of the jackal in rabies control programmes without resorting to extermination. PMID- 7777323 TI - The role of the yellow mongoose (Cynictis penicillata) in the epidemiology of rabies in South Africa--preliminary results. AB - Ninety-seven yellow mongooses were captured in six different localities in South Africa and blood specimens for rabies antibody determination as well as brain and salivary glands for virus isolation were collected. No rabies virus or antibody to it was detected in any of the specimens. Parallel to the field study, two experimental infections were undertaken in which yellow mongooses were artificially infected with serial dilutions of two different rabies isolates (one from a dog and the other of mongoose origin) in order to determine the minimal lethal dose (MLD50), clinical signs, duration of illness, course of the disease, presence of virus in the saliva and salivary glands and development of antibodies to rabies virus. A significantly higher proportion of mongooses inoculated with mongoose virus died than did those inoculated with the dog isolate. However, the clinical signs, incubation period, duration of illness and development of antibodies were independent of the dose of the inoculum. The levels of rabies virus in the saliva and salivary glands were high in all clinically affected animals infected with the mongoose isolate but only one of the two mongooses which died following inoculation of the dog isolate contained detectable levels of virus in the salivary glands. Antibodies to rabies were detected only in the terminal stages of clinical disease. PMID- 7777324 TI - A systematic and population genetic approach to the rabies problem in the yellow mongoose (Cynictis penicillata). AB - This paper reviews recent studies on the biology, systematics and population genetics of yellow mongoose populations in terms of possible implications for the epidemiology of rabies. Based on parallel studies, the existence of three distinct subspecies of yellow mongoose may have a direct bearing on rabies epidemiology; at least subspecific affiliation should be considered as a factor to be controlled for in rabies studies of the species. A direct correlation was found to exist between population genetics, social structure (and vagility) and aspects of the epidemiology of rabies in the yellow mongoose. The high frequency of enzyme polymorphisms restricted to single populations can be understood in terms of the well developed social structure and low vagility of yellow mongooses, which in turn explains the phenomenon of rabies outbreaks being restricted to highly localized foci which may flare up over a period of several years. Further research is required to establish whether predictable population genetic differences exist between high and low rabies-prone populations. PMID- 7777326 TI - The bat-eared fox: a prime candidate for rabies vector? AB - Bat-eared foxes, Otocyon megalotis, are small (3-5 kg), primarily insectivorous carnivores widespread in the more arid areas of southern and East Africa. For many months of the year they live in nuclear family groups, members of which frequently indulge in affiliative behaviour such as play, allogrooming, and huddling. Physical contact between individuals in any particular group is thus common. In addition, groups are non-territorial and intermingle freely at times when exploiting food-rich patches of clumped prey, e.g. individuals foraging for harvester termites, Hodotermes mossambicus. PMID- 7777325 TI - Bat-eared fox behavioural ecology and the incidence of rabies in the Serengeti National Park. AB - This paper provides a brief introduction into some aspects of bat-eared fox biology and social organization that is important to understanding rabies transmission and disease management in susceptible wildlife species (Macdonald 1980; 1993). A detailed description of the effects of two rabies outbreaks on a population of known individuals in the Serengeti National Park is given, Inter- and intrasexual differences in adult mortality rates are reported and discussed. PMID- 7777327 TI - Rabies in bat-eared foxes in South Africa. AB - Rabies in bat-eared foxes was first recognized in South Africa in 1955 and is likely to have been derived from canine rabies introduced to South Africa in 1950. Since then it has become established in this species in the drier western half of the country and the south-western Cape so that rabies now occurs in bat eared foxes adjacent to the peri-urban canine population of Cape Town. Peak incidence was recorded in the early 1980s and the incidence is seasonal with most cases occurring in winter. PMID- 7777328 TI - Social systems and behaviour of the African wild dog Lycaon pictus and the spotted hyaena Crocuta crocuta with special reference to rabies. AB - Differences in the social systems and behaviour of two potentially important hosts of rabies, the African wild dog and the spotted hyaena, may lead to differences in the epizootiology of the disease in the two species. Wild dogs are highly social animals in which pack members are in constant physical contact with each other, but in which inter-pack interactions are rare. Spotted hyaenas are more flexible in their social systems and behaviour. Clan members interact less frequently than do wild dogs, but inter-clan contact rates may be high in high density populations. Rabies transmission within wild dog packs should be rapid, but rare between packs. In spotted hyaenas rabies transmission between clan members may partially depend on the social status of the animals involved and between packs on the density of hyaenas in the area. PMID- 7777329 TI - Rabies in the Masai Mara, Kenya: preliminary report. AB - A serosurvey of rabies antibodies among domestic dogs (Canis familiaris, n = 178), spotted hyaenas (Crocuta crocuta, n = 72) and African wild dogs (Lycaon pictus, n = 18) of the Masai Mara, Kenya, was carried out. Rabies antibodies were found in 9.6% of the domestic dog sera, but all wild dog and hyaena sera were negative. Rabies has been confirmed in this region among the above species as well as in a domestic cat (Felis catus) and a cow (Bos indicus) by fluorescent antibody tests (FAT) and/or histopathology. The disease was confirmed in three wild dogs in 1989 and in a fourth dog in early 1991. In 1992, a spotted hyaena attacked six people, one of whom died; the hyaena brain was positive for rabies. To date, rabies has been confirmed in one domestic cow (n = 22; 4.5%), one domestic cat (n = 9; 11.1%) and five domestic dogs (n = 32; 15.6%). The wild dog cases exhibited paralytic rabies whereas in the hyaena, domestic cat and domestic dogs furious rabies was observed. The dynamics of rabies in this ecosystem is not yet fully understood, but based on these preliminary data it is suspected that domestic dogs play a primary role in its maintenance. PMID- 7777331 TI - Canine rabies. AB - Dog rabies is still epizootic in most countries of Africa, Asia and South America and in these countries dogs are responsible for most human deaths from the disease. The incubation period in dogs may vary from one week to several months and may be influenced by the site of infection and the virus dose and strain. Diagnosis by clinical signs alone is inadequate since many rabid dogs develop dumb rabies which can easily be overlooked and others die without showing signs of rabies. Rabies virus may be excreted in the saliva before clinical signs appear and may lead to infection of an unsuspecting and untreated bite victim. Dogs may recover from clinical rabies and may then intermittently excrete virus in the saliva. Prevention of human rabies depends on the control of canine rabies which can only be achieved by mass-immunization and control of stray dog populations. PMID- 7777330 TI - Aspects of rabies infection and control in the conservation of the African wild dog (Lycaon pictus) in the Serengeti region, Tanzania. AB - Lycaon pictus is amongst the most endangered wildlife species in Africa. In 1990 rabies virus was isolated from the brain of an adult Lycaon found dead in the Serengeti region of Tanzania. One adult and six pups of the same pack feeding on the carcass showed clinical signs and rabies was suspected; within two days they had disappeared and are presumed to have died. Subsequently, two Lycaon packs in the Serengeti National Park were given inactivated rabies vaccine either by dart or by parenteral inoculation following anaesthesia. Lycaon sera which had been collected over the previous two years and sera collected pre- and post vaccination were examined for the presence of rabies virus neutralizing antibody. Three of 12 unvaccinated Lycaon had antibody levels > 0.5 IU/ml; post-vaccination samples from two Lycaon showed increased antibody levels. Between four and ten months post-vaccination, at least four of the vaccinated animals had died from unknown causes. Issues relating to wildlife vaccination and veterinary intervention in conservation are discussed. PMID- 7777333 TI - A dog ecology study in an urban and a semi-rural area of Zambia. AB - Characteristics of dog populations and their accessibility for rabies vaccination were compared in an urban and a semi-rural area in Zambia. A total of 1,190 households were interviewed. In the urban study area (Mutendere, a low income suburb of Lusaka) only 11% of the households kept dogs with a dog:human ratio of 1:45. In the semi-rural area (Palabana) dogs were kept by 42% of households with a dog:human ratio of 1:6,7. In conjuction with the study of the dog populations in these two areas, immunization of dogs against rabies was provided by door-to door visits in both study areas and also through central point vaccination in the urban area. The attitude of the public towards free rabies vaccinations was positive, although some misconceptions regarding indications and modalities of treatment following exposure to suspect dogs were found. Approximately 50% of the dog removals were as a result of disease and the demand for dogs was higher than the supply. Although only information on the owned segment of the dog population was obtained during the study, the proportion of ownerless dogs appeared to be very low. Generally, there is a need for better co-ordination between the different services involved in rabies control in Zambia to enhance the sustainability of vaccination programmes and improve the treatment of persons bitten by dogs. PMID- 7777332 TI - Dog ecology in eastern and southern Africa: implications for rabies control. AB - With an apparent decline in rabies vaccination coverage in dog populations in many parts of eastern and southern Africa, consideration should be given to more effective targeting of rabies vaccination to protect those sectors of the dog population with the greatest capacity to transmit rabies. This paper discusses the potential contributions that dog ecology studies may make to the improved delivery of rabies control measures and the targeting of vaccination programmes in the region. Data requirements on dog population size and structure are discussed, methods for collection of such data are summarized, and the studies on dog ecology carried out to date within the region are reviewed. PMID- 7777334 TI - Features of dog ecology relevant to rabies spread in Machakos District, Kenya. AB - A random sample of households in Machakos District of Kenya was surveyed using personal interviews to determine features of dog ecology relevant to the spread of rabies. A mean of 1.35 dogs/household, a dog to person ratio of 1:9.6 and a mean of 10.4 dogs/km2 were estimated. The male to female ratio was 1:0.67 with 26% of the dog population being less than three months old. The dogs had a mean age of 1.8 years. The proportion of the dogs which fed on household leftovers and waste was 94.7%. Dogs were restricted in 19.4% of the households, while 69% of the dogs spent all of their time free outdoors. One-third of the dog population over three months old had been vaccinated against rabies. Considering the endemic status of rabies in Machakos District, methods which could be devised to control the disease are discussed. PMID- 7777335 TI - The delivery of oral rabies vaccines to dogs: an African perspective. AB - Dog rabies control relies principally on the mass immunization of dogs in order to achieve population immunity levels sufficient to inhibit rabies transmission. In Africa, such high levels of population immunity are rarely achieved due to a number of reasons. Oral immunization has been shown to be an effective means of inducing high levels of immunity in fox populations in several European countries, and this technique has been mooted as a means of overcoming the logistical problems of delivering injectable rabies vaccines to dogs. This paper discusses the requirements for oral rabies vaccines for dogs in Africa and reviews the trials performed to date on baits and baiting systems suitable for the delivery of such vaccines. Issues affecting possible rabies vaccine distribution in the future are discussed and the major research issues still to be tackled are summarized. PMID- 7777336 TI - SAG-2 oral rabies vaccine. AB - The live modified rabies virus vaccine strain SAG-2 was selected from SADBerne in a two step process employing anti-rabies glycoprotein monoclonal antibodies. The first two nucleotides coding for the amino acid in position 333 of the rabies glycoprotein are mutated. Arginine at position 333, which is associated with rabies pathogenicity, was substituted first by lysine and then by glutamic acid. The two nucleotide differences at position 333 in SAG-2 to any of six possible arginine triplets translated into excellent genetic stability and apathogenicity for adult mice, foxes, cats and dogs. The vaccination of foxes and dogs by the oral route provided protection against a lethal challenge with rabies virus. PMID- 7777337 TI - Recombinant rabies vaccines: efficacy assessment in free-ranging animals. AB - With the advancement of recombinant DNA techniques, a number of potent biologicals are available for the oral vaccination of free-ranging animals. Once oral immunogenicity and vaccine safety have been demonstrated, efficacy then becomes of paramount importance. Classical assessment of efficacy is conducted under carefully controlled laboratory conditions, whereas efficacy of oral wildlife rabies vaccination programs, to date, have been assessed by the lack (or occurrence) of field cases of rabies in a vaccinated area. This communication describes an intermediate vaccine efficacy strategy in which self-vaccinated, free-ranging animals from a study site were captured seven months after vaccine laden bait distribution for laboratory rabies challenge. This technique is specifically reviewed in the context of available recombinant products for the consideration of extension towards dog rabies control. PMID- 7777338 TI - Rabies eradication in Belgium by fox vaccination using vaccinia-rabies recombinant virus. AB - Oral immunization of foxes against rabies, by distributing vaccine-baits in the field, has been in progress since 1993 in the whole of the infected area of Belgium (10,000 km2). A vaccinia-rabies recombinant virus (VR-G) was used as vaccine because of its efficacy, safety and heat-stability. The successive campaigns of fox vaccination have induced a drastic decrease in rabies incidence and in 1993 there were no cases of rabies detected in the fox population. A marked decrease of human post-exposure treatments and the elimination of the disease in domestic animals have been the consequence of fox rabies control. PMID- 7777339 TI - Oral rabies vaccination of jackals: progress in Zimbabwe. PMID- 7777341 TI - [Automated gonarthrosis diagnosis]. PMID- 7777340 TI - Bait formulation and distribution for oral rabies vaccination of domestic dogs: an overview. AB - Current efforts to develop oral rabies vaccine baits for domestic dogs are reviewed and new materials (bait matrices, additives, vaccine containers, vaccine modification) for improving bait acceptance and vaccine delivery are suggested. Methods that have been used to evaluate the food or bait preferences of confined and free-ranging animals are summarized, as are the guidelines for bait distribution compiled by the World Health Organization. PMID- 7777342 TI - [The therapeutic principle of hyaluronic acid is very promising]. PMID- 7777343 TI - [What is hyaluronic acid and how does it work?]. PMID- 7777345 TI - Is it safe for pregnant nurses to be exposed to chemotherapy agents? PMID- 7777344 TI - [Effect of hyaluronic acid is examined in clinical studies]. PMID- 7777346 TI - Fundamental immune mechanisms of the brain and inner ear. AB - Because of the blood-brain and blood-labyrinthine barriers, the brain and inner ear were once thought to be immunoprivileged sites. Although these barriers provide protection from inflammatory damage to the delicate structures of the organs, both sites have since been shown to be capable of active immune responses when appropriately stimulated. In the inner ear, perisacular tissue around the endolymphatic sac hosts resident lymphocytes and serves as a site of immunosurveillance. Lymphocytes also enter the inner ear from the circulation, and in the cochlea this occurs via the spiral modiolar vein. Immune responses can protect the labyrinth from infection, but they can also cause bystander injury. Moreover, the cochlea can itself become the target of immune responses that damage hearing. Such autoimmune sensorineural hearing loss can be site specific, with the primary manifestation of the disorder being hearing loss and dysequilibrium. Some of these cases can be diagnosed by antibody or lymphocyte responses to inner ear antigens. Alternately, systemic autoimmune disorders can result in inner ear dysfunction as part of a broader spectrum of disease. Both forms of immune-mediated inner ear dysfunction may respond to immunosuppressive therapies, including steroids, cytotoxic agents, and plasmapheresis. PMID- 7777347 TI - Cerebrospinal fluid leak after translabyrinthine acoustic neuroma surgery. AB - Cerebrospinal fluid leakage is the most common complication of translabyrinthine acoustic neuroma surgery. This retrospective study reviews patients who had translabyrinthine acoustic neuroma surgery at the Gruppo Otologico, Piacenza, Italy, and ENT Department of Bergamo General Hospital, Bergamo, Italy, during the last 6 years. The incidence of postoperative cerebrospinal fluid leakage was 6.2%, and 75% of these patients underwent another surgery to control the cerebrospinal fluid leakage. A modification of translabyrinthine approach was used in patients with highly pneumatized temporal bones to prevent cerebrospinal fluid leakage in these high-risk patients. PMID- 7777348 TI - Detection of Epstein-Barr virus genome in sinonasal undifferentiated carcinoma by use of in situ hybridization. AB - Associations between Epstein-Barr virus and undifferentiated carcinomas of nasopharynx, parotid gland, and thymus have recently been reported. Epstein-Barr virus has also been associated with malignant lymphoma of the nose and paranasal sinuses. These findings raise the possibility that Epstein-Barr virus may additionally be linked to undifferentiated carcinoma of the nose and paranasal sinuses (SNUC), an uncommon but distinctive and highly aggressive neoplasm. Histologically, SNUC consists of small and medium cells, the precise characterization of which often requires immunocytochemical analysis. This study investigates the presence of DNA sequences of Epstein-Barr virus in biopsy specimens of 13 cases of SNUC that were defined immunocytochemically by use of previously reported criteria. In situ hybridization was used to detect Epstein Barr virus genome in different cell types in routinely processed, paraffin embedded tissues. Epstein-Barr virus-specific DNA sequences were detected in tumor cells of SNUC specimens from 5 of the 13 cases examined. No correlation was found between positive hybridization and primary tumor site, morphologic subtype, or disease course. Epstein-Barr virus DNA was detected in 38% (5 of 13) of the SNUC samples analyzed. This finding suggests that this virus may play a role in the pathogenesis of this rare neoplasm. PMID- 7777349 TI - Comparison of modified PhadezymRAST, ImmunoCAP, and serial dilution titration skin testing by receiver operating curve analysis. AB - Improved technology in in vitro tests for allergen-specific immunoglobulin E has led to increased efficiency and faster turnaround times. ImmunoCAP (Pharmacia Diagnostics, Clayton, N.C.) is an in vitro-specific immunoglobulin E test that uses a three-dimensional cellulose solid allergen phase, which allows quick results in 6 hours. In comparison, modified Phadezym-RAST (Pharmacia Diagnostics) uses a two-dimensional solid phase, and results take 3 days to obtain. This study compares the sensitivity and specificity of CAP with that of modified RAST in the detection of specific immunoglobulin E, and it assesses the correlation of the individual class scores of CAP and modified RAST with end points obtained from skin-dilutional end-point titration. The reproducibility of CAP was also assessed. Patients evaluated at the University of Chicago Allergy Clinic who had a history and physical examination consistent with immunoglobulin E-mediated allergy and in whom skin testing was clinically indicated as part of their allergy management, were asked to donate some blood for simultaneous in vitro testing by PhadezymRAST and ImmunoCAP. Testing was performed in batches. Random samples from the CAP batches were chosen for duplicate runs under conditions blinded to the technician. Receiver operating curve analysis was used for comparison of the sensitivity and specificity of RAST vs. that of CAP. We used Pearson product-moment correlation coefficients to compare the correlation of RAST and CAP classes with the end points from skin testing. Our results indicate that the sensitivity and specificity of RAST and CAP are similar, that the classes of these two tests correlate well with the end points from skin testing, and that duplicate samples of CAP also correlate well. PMID- 7777350 TI - Mastoid oscillation: a critical factor for success in canalith repositioning procedure. AB - The canalith repositioning procedure has recently gained controversial recognition as a treatment for benign paroxysmal positional vertigo. Some authors contend that the canalith repositioning maneuver is no more effective than no treatment at all. Unfortunately, its technique has not been uniformly applied and its outcomes have not been uniformly assessed. I have found the use of mastoid oscillation to be critical in the success of this procedure. Another important factor is the time interval between diagnosis and relief of symptoms. Because it is well known that benign paroxysmal positional vertigo can spontaneously resolve after many months, the time frame for comparison should be short. A 1-week time interval was chosen for study purposes. Sixty patients were randomly assigned to three initial groups. The control group (n = 23) was not given any treatment. A second group (n = 27) was given treatment with the canalith repositioning maneuver with mastoid vibration. A third group (n = 10) was assigned to receive the canalith repositioning maneuver without mastoid vibration. Resolution was defined as no symptoms and negative Dix-Hallpike test results. The results showed that none of the control group's symptoms resolved completely in 1 week. Although 60% of those who received the canalith repositioning maneuver without mastoid vibration felt improved, none was free of nystagmus. An overwhelming 92% of those who received the canalith repositioning maneuver with mastoid vibration felt improved, and 70% were free of rotatory nystagmus after only one treatment. A review of all patients diagnosed with benign paroxysmal positional vertigo and treated with the canalith repositioning maneuver with mastoid vibration was also undertaken. In a series of 67 patients with a minimum of four weeks of follow-up, only two have not responded to the canalith repositioning maneuver, yielding a 97% rate of symptom control. PMID- 7777352 TI - Reduced mastoidectomy complications with an open meatoplasty stent. AB - Open-tube stents were compared with standard petroleum gauze packs in meatoplasties after canal-wall-down mastoid surgery to determine whether any difference existed in postoperative complications. Tube stents were associated with much lower incidences of postoperative meatoplasty stenosis and postauricular wound complications in this series. PMID- 7777351 TI - Aphysiologic performance on dynamic posturography. AB - The remarkable ability of the body to maintain balance is the result of central nervous system integration of sophisticated inputs from the vestibular, visual, and somatosensory systems. Strategies by patients with balance dysfunction are aphysiologic when their performance is relatively better on more difficult conditions of sensory conflict than on easier ones. Twenty-two aphysiologic patterns on computerized dynamic posturography were compared with age-matched normal and vestibular patterns. The aphysiologic group performed significantly better than the patients in the vestibular dysfunction group on the most difficult subtests of computerized dynamic posturography, conditions 5 and 6, yet significantly poorer on the easier subtests, conditions 1 through 4. In addition, patients in the aphysiologic group tended to show greater intertrial variability compared with patients in both normal and vestibular system dysfunction groups. A stepwise linear discriminant analysis was used to determine a set of conditions that had significant value in discriminating between the three patient groups. Case studies are presented to further illustrate the clinical usefulness of computerized dynamic posturography testing in the evaluation of patients suspected of having a functional component to their on-feet balance problems. PMID- 7777353 TI - Superiority of the T and N integer score (TANIS) staging system for squamous cell carcinoma of the oral cavity. AB - An alternative to the TNM classification system has been proposed for patients with head and neck cancer. The T and N integer score (TANIS) system adds the integer values of T and N classifications. The TNM and TANIS staging systems were retrospectively evaluated for 186 patients with squamous cell carcinoma of the oral cavity (tongue and floor of mouth). The TANIS system was found to better separate the patients into prognostic groups and allowed a more accurate prediction of disease-free survival. PMID- 7777354 TI - Day care and the incidence of otitis media in young children. AB - OBJECTIVE: This study assesses whether day care is a significant risk variable for otitis media in children younger than 2 years in the United States after controlling for the number of children in the day care group. DESIGN: The computerized data source used is the 1988 Child Health Supplement (N = 17,110) of the National Health Interview Survey (NHIS-CH). SETTING: The NHIS-CH data is a multistage probability sample with clustering and stratification. It represents the civilian, noninstitutionalized population of the United States. PARTICIPANTS: The NHIS-CH sample consists of one randomly selected child from each NHIS household containing a child younger than 18 years. The overall response rate for the NHIS-CH was approximately 90%. For this analysis the focus is on children younger than 2 years (N = 2294). MAIN OUTCOME MEASURES: The NHIS-CH includes a direct questioning of an adult member of the household, usually the mother, about whether the child has ever had frequent or repeated ear infections. RESULTS: After controlling for the total size of the day care group for children younger than 12 months, the previously established relationship between attending a day care center and frequent ear infections is reduced from an odds ratio of 3.17 (95% confidence interval, 1.50 to 6.71) to an odds ratio of 1.34 (not significant; p = 0.60). CONCLUSION: The total size of the day care group is an important intervening variable in the relationship between attending day care and frequent ear infections for children younger than 12 months. The size of the day care group rather than the day care per se is the primary "modifiable risk variable" for many working parents. PMID- 7777355 TI - Clinical and pathologic distinction between primary and metastatic mucosal melanoma of the head and neck. AB - Metastatic mucosal melanoma is extremely rare. Only 0.6% to 9.3% of patients with cutaneous malignant melanoma will have metastases to the mucosa of the upper aerodigestive tract. The records of all patients with mucosal melanoma of the head and neck at the University of California, Los Angeles Medical Center during the past 30 years were reviewed. Patients with primary tumors were separated form those with metastatic involvement from a cutaneous primary site. These two groups were compared for differences in clinical symptoms, histopathologic findings, treatment, and survival characteristics. Frequent sites of metastatic involvement included the base of tongue and nasal cavity. These arose from a variety of cutaneous sites including the trunk and extremities and, in most instances, did not arise until 2 to 7 years after the initial cutaneous lesion. Most of those with metastases to the head and neck mucosa had disseminated disease. The histopathologic distinction between the two groups is described with photomicrographs. Junctional activity in the overlying or adjacent mucosa distinguishes primary mucosal melanoma from metastatic disease, in which the overlying mucosa is usually intact. This difference is useful in determining workup and treatment options. Aggressive surgical resection is suggested in treatment of primary melanomas, whereas surgery is at best palliative in those with metastatic disease. PMID- 7777356 TI - Calvarial bone repair with porous D,L-polylactide. AB - Bone is a storehouse of biologic factors enabling it to regenerate without scar formation. Recombinant technology has made many of these factors available in significant quantity for therapeutic applications. However, a system to deliver recombinant bone-regenerating factors is needed. Biodegradable, biocompatible polymers have shown promise for delivering bone regenerative factors, such as bone morphogenetic protein. The polymer we selected to investigate was racemic D,L-polylactide. Our immediate objective was to engineer porous D,L-polylactide to promote bone ingrowth (osteoconduction). We tested the hypothesis that porous D,L-polylactide implanted in a standard intraosseous calvarial wound would not hinder but would support bone regeneration. Therefore porous polylactide disks (65% void volume) were manufactured with pores < or = 100 microns, < or = 200 microns, and < or = 350 microns; implanted in rabbits' calvariae, and retrieved 1, 2, 4, and 6 months after insertion. Quantitative histomorphometry revealed a possible relationship in the amount of bone ingrowth with increasing pore size over time. The D,L-polylactide disks < or = 350 microns had the greatest quantity of bone ingrowth (< or = 0.05). However, a disturbing finding was the multinucleated giant cell response associated with all implanted disks. We speculate these cells may have produced an inhospitable environment stifling osteoconduction. Consequently, postsynthesis engineering refinements of D,L polylactide to eliminate the giant cell response are crucial before loading with bone morphogenetic protein. PMID- 7777357 TI - Effects of halothane on mucociliary activity in vivo. AB - The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% +/- 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% +/- 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% +/- 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% +/- 2.7% (p < 0.05, n = 5). There was also an initial increase in respiratory rate from 62 +/- 7.3 to 89 +/- 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probably due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity. PMID- 7777358 TI - Use of the guinea pig flank flap in skin flap research. AB - A variety of flaps in laboratory animals have been designed that propose to parallel the behavior of human skin under different experimental conditions. In the search for a readily available and affordable island skin flap model that combines reliable anatomy with a pedicle of substantial size, we have designed in the guinea pig a cutaneous flap based on the superficial circumflex iliac artery and vein. In 22 adult female Hartley guinea pigs, an 8 x 4 cm flank flap based on the superficial circumflex iliac pedicle was raised, and its characteristics were evaluated for applications to skin flap research. Dermofluorometric studies were performed that confirm the vascularity of this flap, and 100% survival of the flap was seen 5 days after surgery in all animals. Of particular benefit was the demonstration that both afferent and efferent blood samples can be taken from the pedicle directly, which allows for the direct quantification of plasma markers after physiologic insults to the skin flap, such as burn or ischemia. This anatomically reliable and easily dissected flap lends itself well to preliminary skin flap research and may contribute to standardization of a model for further studies examining the behavior of skin microcirculation under adverse physiologic conditions. PMID- 7777360 TI - Hemangioendothelioma of the maxillary sinus. PMID- 7777359 TI - Inhibition of head and neck squamous cell carcinoma cell lines by transforming growth factor-beta. AB - Transforming growth factor-beta is known to be a potent autocrine growth inhibitor produced by a wide variety of cells, including cells of the immune system. Other investigators have noted that the growth of nontransformed keratinocytes is inhibited by transforming growth factor-beta, whereas various carcinoma cell lines are resistant to these effects. Head and neck squamous cell carcinoma cells are known to have surface receptors for this cytokine. We thus assessed the effect of transforming growth factor-beta on the growth of head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines were incubated with varying concentrations of transforming growth factor-beta, and cytotoxicity was evaluated with a methylene blue colorimetric assay. After culturing in transforming growth factor-beta for 4 days, inhibition of growth was detected in CAL-27 (maximal inhibition at 5.0 ng/ml), UMSCC-1, and UMSCC-19 (maximal inhibition at 50 ng/ml) cell lines. One other cell line, UMSCC-8 was found resistant to the inhibitory effects of transforming growth factor-beta. Kinetics analysis experiments revealed minimal inhibition before day 2 of incubation, at which time inhibition increased linearly to day 4. Assessment of double-stranded DNA fragmentation suggested that DNA fragmentation occurs before significant cytotoxicity. Electron microscopic analysis and gel electrophoresis of extracted DNA revealed morphologic features consistent with apoptotic cell death. Our findings indicate that transforming growth factor-beta significantly inhibits the growth of head and neck squamous cell carcinoma cell lines by inducing apoptotic cell death. PMID- 7777361 TI - Atypical vestibular neuritis: a case report. PMID- 7777362 TI - Reversible blindness secondary to acute sphenoid sinusitis. AB - Sphenoid sinusitis is an elusive diagnosis with significant morbidity if not diagnosed and treated promptly. We have reported an unusual case of acute sphenoiditis mimicking Gradenigo's syndrome. This resulted in virtual bilateral blindness that entirely resolved with aggressive surgical and medical treatment. It is recommended that sphenoid sinusitis be strongly considered in patients with acute headache and fever. A detailed cranial nerve examination should be performed, and CT scans of the skull base and paranasal sinuses should be obtained. Immediate surgery is strongly recommended for acute sphenoid sinusitis at the first suggestion of a complication and in those patients not promptly responding to medical therapy. It is apparent that irreversible damage to the optic nerve can occur before the development of gross intraorbital pathology. Therefore we believe that delaying surgery until the visual acuity is worse than 20/60, as advocated by some authors, may not be in the patient's best interest. Surgery should be directed at removing the purulent material, obtaining cultures, removing irreversibly diseased mucosa, and maintaining drainage of the sphenoid sinus. PMID- 7777364 TI - Cytomegalovirus sinusitis in a patient with acquired immunodeficiency syndrome. PMID- 7777363 TI - Odynophagia caused by inadvertent blister pack ingestion: a case report. PMID- 7777365 TI - Solitary extramedullary plasmacytoma of the epiglottis: a case report and review of the literature. PMID- 7777366 TI - Wegener's granulomatosis presenting as ophthalmoplegia and optic neuropathy. PMID- 7777367 TI - Subcutaneous bronchogenic cysts and sinuses. PMID- 7777368 TI - Lemierre's syndrome: two cases of postanginal sepsis. AB - Lemierre's disease consists of suppurative thrombophlebitis of the IJV in the presence of oropharyngeal infection and can be complicated by septic pulmonary emboli. If a patient has an oropharyngeal or deep neck infection and neck pain suspicious for IJV thrombosis, a CT or MRI is warranted to establish the diagnosis. Blood cultures should be obtained to establish the responsible organism. In most cases F. necrophorum, an anaerobic bacterium, is responsible for the sepsis. Once the diagnosis of Lemierre's disease is made, long-term, high dose intravenous antibiotics with beta-lactamase anaerobic activity should be initiated. In cases with persistent sepsis and emboli despite appropriate medical management, ligation or excision of the IJV should be performed. Finally, if there is clinical or radiologic evidence of retrograde cavernous sinus thrombosis, the use of anticoagulants should be considered. PMID- 7777369 TI - Acquired laryngomalacia: resolution after neurologic recovery. PMID- 7777370 TI - Intrinsic infiltrating intramuscular laryngeal lipoma. PMID- 7777371 TI - Parotid hemangioma in infancy: diagnosis with technetium 99m-labeled red blood cell pool imaging. PMID- 7777373 TI - Eurocancer 1994. Paris, France, 26-29 April 1994. Abstracts. PMID- 7777372 TI - Lingual necrosis as the initial symptom of small cell carcinoma. PMID- 7777374 TI - [Epidemiology of Creutzfeldt-Jakob disease]. AB - Creutzfeldt-Jakob disease is a rare disease (incidence < 1 case per million inhabitants), reported in all continents. Certain characteristics are constant from one country to another: mean age of onset: 65 years, duration of the disease: about 6 months, sex ratio close to 1 and approximately 10% of familial cases. The geographical sites of this disease identified in Chile, Israel and Czechoslovakia suggest certain genetic and/or environmental risk factors. The principal environmental factor implicated is scrapie in sheep, especially in these regions. Genetic studies have demonstrated the presence of apparently causal mutations of the PrP gene and a high risk of CJD associated with certain normal polymorphisms of this gene (codon 129). Certain grafts (dura mater, cornea) and treatment by extracted growth hormone are responsible for iatrogenic transmission. Multicentre epidemiological studies recruiting a large number of cases are needed to define the risk factors of this disease. PMID- 7777375 TI - [Electrophysiology of transmissible encephalopathies]. AB - The purpose of electrophysiological studies during the evolution of spongiform encephalopathies or prion diseases is to describe the changes of spontaneous or evoked electroencephalographic activity in natural and experimental diseases (natural and experimental scrapie, Kuru and Creutzfeldt-Jakob (CJ) disease in man and in different animal models) and to establish or to propose an action mechanism of the infectious agents. In the aim, the changes of electroencephalogram (EEG) and evoked potentials are described. Generally these modifications constitute an excellent and early marker of the initial phases of pathological mechanisms, replication of the agent and the cell membranes alterations. The changes of the sleep organisation occur generally later with the beginning of the clinical phase, just at the end of incubation period. The typical changes of EEG during the human CJ disease are rare in the experimental diseases. However, with animal models, it is possible to demonstrate the very univocal character of these diseases, creating pathophysiological modifications whose nature, origin and evolution are very comparable, with characteristic triade (loss of neurons, gliosis and spongiosis) and specific alterations of gabaergic, dopaminergic and inhibitory processes. PMID- 7777376 TI - [A funny story]. PMID- 7777377 TI - [Neuropathology of non conventional infectious agents or prions]. AB - The neuropathological diagnosis of infections by non conventional agents relies on four lesions: astrocytic gliosis (cell hypertrophy and proliferation) usually contrasting with absent mononuclear cell infiltrates (lymphocytes, monocytes macrophages, and/or microglia) revealed by conventional techniques, and neuronal loss in the most affected areas are little specific findings. Amyloid plaques that are inconstantly found, and spongiosis of gray matter, a characteristic and very frequent finding, are most specific. PrP immunohistochemistry brings additional data. The main diagnostic difficulties are emphasized, and guidelines for Pathological studies are recalled. PMID- 7777378 TI - [Human spongiform encephalopathies]. AB - Clinical descriptions of Creutzfeldt-Jakob disease by the classical authors are compared with 209 transmitted cases at NIH between 1968-1992. Clinical comparison between Kuru, Gertsmann-Straussler-Sheinker Syndrome and Creutzfeldt-Jakob disease. Fatal Familial Insomnia is included into the latter. Familial forms: new acquisitions. PMID- 7777379 TI - [Prion protein: structure, functions and polymorphisms associated with human spongiform encephalopathies]. AB - Transmissible subacute spongiform encephalopathies (TSSE), also known as prion diseases, are rare neurodegenerative disorders of both humans and animals. The biochemical hallmark of these diseases is an accumulation in the brain of an abnormal form of the host-encoded prion protein (PrP). This pathological accumulation could result from a protein conformational change under the influence of unknown factors. The normal function of PrP is unknown. The abnormal form is thought to induce neurodegeneration when experimentally or accidentally introduced in recipient hosts. Such a possibility would explain the transmissible character of these diseases illustrated in humans by iatrogenic contamination. Considerable attention has been focused on the host PrP gene and its relation with the genetic susceptibility of humans and animals. Mutations in PRNP, the gene which encodes PrP in humans, are present in 16% of the patients and might be causative. In patients without any PRNP mutation, a coding polymorphism (129 Met/Val) defines a predisposing factor. Since few years, important progress in the molecular genetics of TSSE in both humans and animals have been performed and point out that the development of different forms of these diseases, experimental, iatrogenic or spontaneous, are strongly dependent on the primary structure of the host PrP. PMID- 7777381 TI - [Manipulation of prion in laboratory: precautions and possible methods of disinfection]. PMID- 7777382 TI - [Nature and physicochemical and biological properties of non conventional transmissible agents or prions: consequences for public health]. AB - Transmissible spongiform encephalopathies (TSE) are rare lethal diseases induced in humans and animals by unconventional agents (TSA) named also prions or virinos. TSA/prions have unconventional properties; in particular, they resist to almost all the chemical and physical processes which inactivate conventional viruses. Natural history of TSE indicates that organs are infectious a long time before the appearance of the clinical symptoms. The only specific marker of the TSA infections is the post-translational accumulation of the host encoded protein PrP (Prion Protein). Iatrogenic Creutzfeldt-Jakob disease (CJD) cases have been described after neurosurgery, treatment with pituitary derived hormones, and cornea and dura mater grafting. TSA associated infectivity is depending upon the nature of the organ in a given infected individual: central nervous system has the highest infectivity, spleen and lymph nodes a medium infectivity, and organs like bone or skin do not harbor any detectable infectious particle. Therefore, donors with neurologic history must be excluded and treatment with pituitary derived hormones should be considered as potentially infected with TSA, and excluded. PMID- 7777380 TI - [Prion, from crazy cows to iatrogenic Creutzfeldt-Jakob disease. Which risk in laboratory or in hospital?]. AB - The long latency time, without any characteristic clinical sign, of transmissible degenerative encephalopathies, the transmissibility of the called "prion" infectious agent, associated with its exceptional resistance to normal inactivation methods, are resulting in accidental transmissions, both human (Creutzfeldt-Jakob disease), and animal (bovine spongiform encephalopathy). Among data about physical and chemical inactivation methods tested, we retain, to avoid professional or iatrogenic transmissions in the laboratory or in hospital, steam autoclaving and sodium hypochlorite or hydroxide treatment. But inactivation shall not be performed using the current processes as regarding parameters such as temperature, concentration and duration of exposure. PMID- 7777383 TI - [Bovine spongiform encephalopathy]. AB - A new Transmissible Sub-acute Spongiform Encephalopathy (TSSE) appeared in 1986 in the bovine species, mainly concerning Great Britain where more than 100,000 cases have now been identified. This review describes the features of the disease that showed it belonged to this particular group of diseases. The currently available hypothesis about the origin of the disease, in Great Britain as well as in other countries where it has also been recognized, are presented. Lastly, the potential risks for the future, in the bovine species but also for other animal species or man, are discussed, in light of the known experimental data. PMID- 7777384 TI - [Scrapie in sheep and transmissible encephalopathy of the mink]. AB - Scrapie in sheep and goat is the prototype of the group of the transmissible spongiform encephalopathies which affect man and some animal species, notably other ruminants with bovine spongiform encephalopathy (BSE) and chronic wasting disease of wild ruminants. Transmissible mink encephalopathy (TME) is a rare disease of ranch-raised mink caused by exposure to a contaminated food ingredient in the ration scrapie, unrecognised BSE-like disease...). There is clinical and pathological similarities between TME and scrapie. These diseases share the following characteristics: a prolonged incubation period; a progressive, debilitating, neurological illness (always fatal); pathological changes confined to the central nervous system (vacuolisation, neurological loss, astrocytosis); the presence of scrapie-associated-fibrils (SAF) in brain tissue; and absence of detectable inflammatory or immune responses. The genetic origin of scrapie in sheep and the natural transmission of these spongiform encephalopathies are discussed. PMID- 7777385 TI - [Juvenile form of Creutzfeldt-Jakob disease. Clinical and neuropathological aspects]. AB - Creutzfeldt-Jakob disease in young people is frequently iatrogenic due to growth hormone cadaveric treatment. Ataxia and diplopia are the main symptoms at onset, and the absence of dementia and of neuroradiological and biological abnormalities is striking. The proof of the disease is given by histological examination (spongiosis, neuronal loss, astroglial proliferation, no inflammatory signs). Amyloid plaques are frequent in these iatrogenic cases. PrP storage in brain is recognised by immunohistochemistry and western-blot. Transmission to animals proves the power of the disease to be transmitted. The transmission by inoculation of a buffy coat from one patient and the recorded cases after blood transfusion justify it is necessary to exclude extractive growth hormone recipients from blood and organ donors. PMID- 7777386 TI - [Biological aspects of Creutzfeldt-Jakob disease related to the extractive growth hormone]. AB - Today 34 young patients have been infected by the Creutzfeldt-Jakob Disease (CJD) agent in France after treatment with pituitary derived growth hormone. 974 individuals received potentially contaminated batches of hormone. The authors then investigated the genetic structure of the prion protein (PrP) gene at the codon 129 in 32 of the 34 CJD patients. Their results show that all are homozygous, 50% of the individuals of the control group being heterozygous. These data strongly suggest that it may exist a genetic susceptibility to the early development of CJD in infected individuals. PMID- 7777387 TI - [Child kidnapping and organ trafficking]. PMID- 7777388 TI - [Acute manifestation of constitutional hypoketotic organic aciduria]. PMID- 7777389 TI - [Multiple acyl-CoA dehydrogenase deficiency. Report of 2 siblings]. AB - The authors report on two siblings with a multiple acyl-CoA dehydrogenase deficiency. The first child died from a Reye's syndrome when he was 9 month-old. The diagnosis was made in the neonatal period in his brother. Early treatment with glucose and carnitine should prevent acute attacks. PMID- 7777391 TI - [Severe visceral leishmaniasis with hepatic involvement. Diagnostic value of the immunoblotting serologic technic]. AB - The case of a 13 year old boy with a severe form of visceral leishmaniasis (VL) mimicking portal hypertension and of unfavorable outcome is presented. The authors stress the usefulness of investigating humoral immune response by using Western Blot assay in order to confirm the diagnosis when the parasite cannot be isolated. Since VL may be responsible for death if the treatment is delayed, screening of the disease in children presenting with chronic liver disease is important in endemic area. PMID- 7777390 TI - [Total thyroidectomy in a young girl presenting C cell hyperplasia at the time of a family screening for medullary carcinoma of the thyroid gland]. AB - The authors report on the case of a 5,8 year-old girl whose father died of medullary thyroid carcinoma. When she was 4,5 year-old, her physical examination was normal but plasma calcitonin and katacalcin (PDN-21) levels were abnormally high in response to pentagastrin infusion. Total thyroidectomy was performed and immunohistochemical staining showed confluent C-cell hyperplasia. No recurrence occurred in this patient over four years on follow-up. PMID- 7777392 TI - [Recurrent cutaneous herpes in the newborn and acyclovir]. AB - The authors report two cases of cutaneous recurrent herpes occurring after a neonatal herpes simplex virus type 2 (HSV2) infection and comment on the role of acute or suppressive therapy by aciclovir (ACV). The two infants were not treated by ACV after the neonatal period. None of the recurrent cutaneous herpes episodes was followed by viral widespread. One case reported by Bergstrom et al on a relapse of HSV2 encephalitis occurring after a cutaneous herpes in a child argues for the use of ACV in recurrent herpes. However, ACV might alter host defense response to HSV2 infection in neonates and children. Thus, it seems not yet recommended to use ACV either as acute or suppressive therapy in recurrent cutaneous herpes unless a progression of the viral disease is noted. PMID- 7777393 TI - [Hydroxy-methyl-glutaryl-coenzyme A lyase deficiency manifesting as Reye's syndrome in a 3-year-old girl]. AB - The authors report on one case of 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HMG-Co A lyase) deficiency in a 3 year-old girl, presenting as Reye's syndrome. Urinary organic profile suggested this inherited metabolic disease; decreased activity of HMG-Co A lyase was demonstrated in cultured fibroblasts. The metabolic etiologies of Reye's syndrome are summarized; clinical, biological, and therapeutic assessment of HMG Co A lyase deficiency are developed. The pattern of organic aciduria must be studied in all patients presenting with Reye's syndrome. PMID- 7777394 TI - [Cranio-cerebral gunshot wounds in civilian practice in children]. AB - The circumstances and the prognosis of six gunshot craniocerebral wounds in civilian children are presented. The cause is a suicide in two cases and an accident in four cases. In three out of these four cases, another person is responsible for this accident, an adult two times, a child in one case. When the accident is due to a child, it is always by play and one time the accident is the autofact of a 2-year-old boy. In all cases, the fire arm was loaded and an adult's imprudence is present. The mortality is important (4/6). More than the initial clinical state, the seriousness of which is not a pejorative indice, the prognosis is subordinated to the CT scan aspect about the missile tract, and to the initial value of the intracranial pressure. PMID- 7777396 TI - [Does the time change affect school children?]. AB - The aim of the study was to determine in young pupil the physiological effect of a 1 hour earlier awakening (summer time) by measuring: the salivary cortisol level. Results showed that the cortisol circadian rhythm synchronized with summer clock time after remaining synchronized with winter time (previous rhythm) for 15 days at least. PMID- 7777395 TI - [Effectiveness of and tolerance to human recombinant erythropoietin in the treatment of kidney failure anemia in children undergoing continuous peritoneal dialysis. Multicenter study]. AB - Eight young children with renal failure, undergoing continuous peritoneal dialysis (CDP) and presenting an anemia (hemoglobin level [Hb] 57 to 89 g/l) were treated by subcutaneous recombinant human erythropoietin (rHu EPO) twice weekly. The initial dose of 75 U/kg was adjusted to induce progressive increase of Hb with a target level of 100-120 g/l. Treatment duration was 24 weeks in five of these children and 10 to 13 weeks in the three others. In seven cases out of eight, anemia was corrected. The target Hb level was reached in 3 to 21 weeks with rHu EPO doses of 150 to 300 U/kg/w (mean: 200 U/kg/w) for four children without recent transfusion; then the median maintenance dose was 135 U/kg/w (range: 50-300 U/kg/w). In only one patient, Hb never reached a level higher than 77 g/l despite weekly dose of 350 U/kg, a reticulocytosis of 5.6%, rHu EPO treatment lasting up to 24 weeks and the absence of iron deficiency. In any case, no transfusion was necessary after the first day of rHu EPO treatment. In three patients, the increase of a preexisting hypertension required the adaptation of antihypertensive treatments. One patient presented a marked thrombocytosis. In conclusion, twice-a-week subcutaneous injections of 75 to 150 U/kg of rHu EPO appear to be well tolerated and effective in the treatment of anemia of CPD children. PMID- 7777397 TI - [Two-stage repair of microtia]. AB - Modifications of the total ear reconstruction technique allowing a two-stage procedure is described. However this is only possible if the soft tissue has not yet been damaged by previous plastic surgery or tympanoplasties. The framework sculpture is improved in order to obtain a posterior conchal wall at the first stage without using a skin graft. A tissue expander is used during the operative time in order to improve the framework coverage. A bone anchored hearing aid is preferred to tympanoplasty when necessary, for bilateral microtia. This method is effective and does not compromise the skin qualities. The osteointergrated implant is put in place during the second external ear reconstruction stage. The total hospitalisation period is no longer than 8 days. PMID- 7777398 TI - [Family violence and adolescence]. AB - Intrafamilial violence represents a vast topic, even if one limits the subject to the nuclear family. Indeed it includes violence from parents to the child, violence between brothers and sisters, conjugal violence and violence exercised by the child to his parents. Although one can differentiate the types of violence (physical, sexual, and psychological), they often coexist within the same family. Adolescence favors the onset or the reactivation of familial violence; this violence often has repercussion on the psychological equilibrium of the adolescent. Very little is written about parents abused by one of their children (usually an adolescent). This phenomenon is relatively unrecognized and its frequency probably under-estimated. It points to a distortion in parent to child relationship. Therapeutic and/or socio-educational approach must be directed toward both the victim and the aggressor. PMID- 7777399 TI - [Cachectic diencephalic tumor]. PMID- 7777400 TI - Transformation of the cardiovascular program. Leadership and organization. AB - The development of this organizational innovation continues to provide many challenges and opportunities for all involved. The authors emphasize that although cost containment is perhaps the most noticeable effect thus far, it is not the central goal of this endeavor. Obviously, it is important to be conscious of reducing costs in this very competitive health-care environment where quality of care is in danger of being substituted for lower-priced care. The challenge before all of us is to maintain excellence and efficiency less expensively within a collegial and risk-willing environment, as external forces seem to be countercurrent to these efforts. We hope that this new model for providing cardiovascular services within the institution will allow us to continue to improve our tradition of excellence in clinical care and will help us in retaining an environment and spirit conducive to the generation of new knowledge. The more long-lasting result achieved to date is the level of creativity and commitment demonstrated by all staff toward our common vision. The other articles in this issue of Nursing Clinics exemplify the collaborative spirit of our CVP and offer some initial evidence about the early effects of these changes. PMID- 7777401 TI - Restructuring. An integrated approach to patient care. AB - As scientific advances in biochemistry shaped the health-care system since World War II, the projected advances in molecular biology will drive the system of the future. With each scientific advancement or new technology there will continue to be the need for efficient organizations to provide acute care to the patients who will benefit most. Despite numerous projections about the viability of the acute care hospital as we know it and vigorous redirection of services to the patient at home in ambulatory settings or in their community, it is crucial for nurses to take a leadership role in developing long-term approaches to patient care delivery systems for the acute care hospital of the future. PMID- 7777402 TI - Clinical practice guidelines for quality patient outcomes. AB - In response to environmental changes brought about by the debate over health-care reform, hospitals are seeking means to decrease costs while improving quality. By examining the process of health-care delivery, problems in the system can be highlighted for further investigation. Development of clinical practice guidelines by an interdisciplinary team can be an effective approach to decrease undesirable practice variation, standardize appropriate resource use, and measure the effectiveness of care through defined expected-patient outcomes. By ensuring the appropriate, efficient, and effective delivery of health care, savings in cost can be realized by the elimination of duplication, rework, and waste. PMID- 7777403 TI - Peer review. AB - Peer review is a major component of a professional practice and shared governance model in which professional staff nurses are given responsibility for practice and patient outcomes. Careful planning is necessary for the development of a peer review program. Components include definition of roles, responsibilities, and performance standards, as well as the development of an evaluation tool and process. Peer review affords nurses many opportunities for growth and development and allows them to develop communication, evaluation, and presentation skills. The concept of peer review may expand to meet the needs of changing health-care delivery models. PMID- 7777405 TI - Facilitating continuity of care. The role of the patient care coordinator. AB - Continuity of care is essential for children with cardiac disease. The PCC works to ensure that these children continue to receive necessary care postdischarge. By collaborating with members of the health-care team, the PCC is able to coordinate appropriate services for patients in the Cardiovascular Program. The PCC acts as a resource for the interdisciplinary team by identifying postdischarge care options within the community. The PCC also furnishes information to community providers about individual patient care needs. Educating payers in regard to assessed postdischarge needs is another facet of the PCC role. In essence, the PCC provides a link among patients, families, interdisciplinary team members, community providers, and payers. This link facilitates continuity of care for patients in the Cardiovascular Program. PMID- 7777404 TI - The role of the cardiovascular social worker. AB - The clinical social worker is an integral component of the Integrated Care Model used in the Cardiovascular Program at Children's Hospital (Boston). This article provides the reader with an understanding of the social worker's role with families and as part of the interdisciplinary team. Case examples are used to illustrate the key components of clinical social work practice, including crisis intervention, solution-focused treatment, and grief counseling. The importance of maintaining sensitivity to cultural differences in working with families is discussed. PMID- 7777406 TI - Parent participation. AB - Ultimate care of the critically ill child is contingent on a parent-professional partnership that acknowledges both the needs and the strengths of families. In providing pediatric care, parent participation maintains and empowers parents to care for their child. Models of care must include programs that support reempowerment rather than dependence of families. The challenge of including parents as partners in care is one of the most rewarding privileges and responsibilities of pediatric nurses. PMID- 7777407 TI - Dyslipidemias in childhood. An overview. AB - This article reviews the current screening and treatment guidelines for dyslipidemias in the pediatric and adolescent populations. In addition, the components of a comprehensive lipid program are reviewed. PMID- 7777409 TI - Cardiovascular manifestations of pediatric HIV infection. AB - Infection with human immunodeficiency virus (HIV) has become a major pediatric health concern in the United States and around the world. Pediatric HIV infection is a multisystem illness that presents an ongoing challenge to practicing nurses. Most clinical cardiovascular diseases in children with HIV have been underreported, and often are clinically occult. The preclinical detection of cardiovascular abnormalities results in early therapeutic interventions and reduces cardiovascular morbidity and mortality. Cardiovascular involvement is important in the natural history and prognosis of HIV infection. PMID- 7777408 TI - Current management of congestive heart failure in infants and children. AB - Although the general goals of therapy for the medical and nursing management of CHF in children have not changed in the last decade, advances have been made in understanding the unique characteristics of the neonatal heart and tailoring therapy to best support cardiac function (Table 6). In addition, strides have been made in manipulating the loading conditions of the ventricle to enhance cardiac output, which has fostered the development of new therapeutic agents and more aggressive treatment of these patients with improved outcomes. In situations in which the infant is unresponsive to therapy, surgical intervention is now done at an earlier age with good results. When surgery is not an option and the patient continues to deteriorate despite maximum medical management, mechanical support can be instituted as a bridge to transplantation. PMID- 7777410 TI - Advances in the treatment of aortic stenosis across the lifespan. AB - With these results, the pulmonary autograft constitutes the valve of choice for the left ventricular outflow tract in children of all ages, as well as adolescents and adults. Because there is a growth potential, permanent relief from LVOT obstruction might become possible at any age, especially in the number of infants with critical aortic stenosis who survive a valvotomy or repair of interrupted aortic arch during infancy, but return with multiple level outflow tract obstructions early in childhood. If, however, a child is at risk for developing endocarditis or has a history of cardiac infections, it may be a wise choice to use a homograft initially and replace it later with an autograft when the homograft degenerates. PMID- 7777412 TI - Overview of pediatric arrhythmias. AB - Cardiac arrhythmias are being depressed with increased frequency in the pediatric population. Causes of pediatric arrhythmias in the general population include severe metabolic or electrolyte disturbances, drug toxicity, and chest trauma. Repairs of complex congenital heart disease have frequently left this population with persistent or recurrent postoperative arrhythmias. The diagnosis, evaluation, and management of pediatric arrhythmias requires nurses to be skilled in hemodynamic assessment and arrhythmia detection. The registered nurse's grasp of developmental issues and family education is vital in providing quality care to families dealing with these diagnoses. PMID- 7777411 TI - Patient care for interventional cardiac catheterization. AB - This article describes the current management of patients undergoing an interventional cardiac catheterization. New catheters, monitoring equipment, and standards for skilled personnel have allowed for more aggressive and definitive treatments for improving the life of a fragile patient. PMID- 7777414 TI - Implantable cardioverter defibrillator therapy: 15 years experience and future expectations. Proceedings of an international symposium. Paris, October 21-22, 1994. PMID- 7777413 TI - Inhalation of nitric oxide. An innovative therapy for treatment of increased pulmonary vascular resistance. AB - Critical care of patients during pulmonary hypertensive crises is difficult and treatment is hazardous. Conventional therapy has relied on hyperventilation with oxygen and the use of nonselective intravenous vasodilators. The limitations of this approach have prompted clinical investigations of new therapeutic modalities based on recent advances in vascular biology. Inhaled nitric oxide can be used selectively to manipulate the pulmonary vasculature and treat a variety of pulmonary hypertensive disorders. Preliminary studies appear promising as results of properly conducted trials to evaluate efficacy and toxicity are awaited. PMID- 7777415 TI - Implantable cardioverter defibrillator therapy: 15 years experience and future expectations. In the beginning: from dogs to humans. PMID- 7777417 TI - Optimizing defibrillation through improved waveforms. AB - Defibrillation of the heart is achieved if an electrical current depolarizes the majority of the unsynchronized fibrillating myocardial cells. The applied current or the corresponding voltage described as a function of time is called the waveform. In pacing, to stimulate myocardial cells close to the electrode, a relatively low voltage is needed for a relatively brief duration. However, in defibrillation, approximately a 100-fold higher voltage is needed and achieved by the use of capacitors. The exponential voltage decay of a capacitor during its discharge determines the basic waveform for defibrillation. In an attempt to lower the energy needed for defibrillation, the steepness of the decay (different capacitances), the duration (fixed duration waveforms) or tilt (fixed tilt waveforms), or the initial polarity can be changed. Additionally, the polarity of the electrodes can be reversed during the discharge of the capacitor once (biphasic waveform) or twice (triphasic waveform). If two capacitors and defibrillation pathways are available, bidirectional defibrillation pulses can be delivered sequentially. In humans, the original standard waveform used with endocardial leads was a single monophasic pulse delivered by a 125-microF capacitor using the endocardial right ventricular electrode as cathode. It is now known that a reversal of the initial polarity and a reversal of polarity during capacitor discharge may significantly lower the energy needed for defibrillation, thereby preventing formerly frequent failures of defibrillation with endocardial lead systems. The use of sequential pulses showed no or only slight reductions of energy requirements and was abandoned due to the additional electrode needed. The use of a smaller capacitance (60-90 microF reduced maximum energy output but generally did not reduce energy requirements for defibrillation. However, with more efficient electrodes, smaller capacitances that will help to reduce the size of the defibrillator might be used. Thus, today defibrillation is optimized with respect to energy, capacitor size, and ease of implantation if an approximately 90-microF capacitor is used to deliver a biphasic pulse via a bipolar lead system using the right ventricular electrode as anode. PMID- 7777416 TI - Correlation among fibrillation, defibrillation, and cardiac pacing. AB - An electrical stimulus must create an electric field of approximately 1 V/cm in the extracellular space to stimulate myocardium during diastole. To initiate fibrillation by premature stimulation during the vulnerable period or to defibrillate, an extracellular electric field of approximately 6 V/cm is required, a value approximately six times greater than that necessary for diastolic pacing. Yet, the current strength of the pulse given to the stimulating electrode to initiate fibrillation or to defibrillate is much greater than six times the diastolic pacing threshold. The ventricular fibrillation threshold is typically 40 times greater than the diastolic pacing threshold expressed in terms of current. The defibrillation threshold in terms of current is typically thousands of times greater than the diastolic pacing threshold. The reason that these thresholds vary so much more in terms of stimulus current than in terms of extracellular potential gradient is that each of the three thresholds requires creation of the required potential gradient at different distances from the stimulating electrode. Pacing requires a potential gradient of approximately 1 V/cm only in a small liminal volume of tissue immediately adjacent to the electrode. Initiation of ventricular fibrillation by premature stimulation during the vulnerable period requires a potential gradient of approximately 6 V/cm about 1 cm away from the stimulating electrode to allow sufficient space for the central common pathway of a figure-eight reentrant circuit to form. Since the potential gradient falls off rapidly with distance from the stimulating electrode, a stimulating current about 40 times greater than the diastolic pacing threshold is required to generate an electric field of 6 V/cm approximately 1 cm away from the stimulating electrode. Defibrillation requires an electric field of approximately 6 V/cm throughout all or almost all of the ventricular myocardium. Since some portions of the ventricles can be more than 10 cm away from the defibrillation electrodes, a shock of several amps is required to create this field, a current thousands of times greater than the pacing threshold. PMID- 7777418 TI - Programmable VT detection enhancements in implantable cardioverter defibrillator therapy. AB - This report describes the distribution of automatically measured values of enhanced arrhythmia detection parameters such as "rate stability" and "rate onset" in various forms of spontaneous arrhythmia episodes in patients treated with a new, third-generation, tiered therapy implantable cardioverter defibrillator (ICD). The study population consisted of 27 patients who received the Ventak PRxII cardioverter defibrillator, which provides extensive diagnostic options such as electrogram storage capabilities, and the ability to store measured values of additional arrhythmia detection parameters such as rate stability and rate onset during spontaneous arrhythmia episodes. During a follow up period of 11.1 +/- 5.2 months, this device detected 264 arrhythmia episodes. The analysis of stored electrograms revealed 13 episodes of sinus tachycardia, 52 episodes of atrial tachyarrhythmias, and 201 episodes of monomorphic ventricular tachycardias (VTs). The mean measured values of rate stability and rate onset were: 2.2 +/- 0.9 msec, 0% in sinus tachycardias; 41.0 +/- 24.1 msec, 8.5% +/- 9.5% in atrial tachyarrhythmias; and 7.8 +/- 6.0 msec, 30.6% +/- 12.1% in monomorphic VTs. There was a wide zone of overlapping measured values for rate stability and rate onset in ventricular and nonventricular rhythms. No episode of VT showed a measured rate stability criterion > 35 msec. The subanalysis of arrhythmia episodes presenting with a heart rate < 160 beats/min revealed no episode of VT with a rate stability value > 24 msec. The calculated, rate dependent specificities for these programmed rate stability parameters in detecting VTs were 46.2% and 81.8%, respectively. The analysis of the rate onset algorithm revealed no comparable relationship between sensitivity and specificity in the detection of VTs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777419 TI - Implantable cardioverter defibrillator lead technology: improved performance and lower defibrillation thresholds. AB - The performance of an ICD system depends, in part, on the effectiveness with which the lead system functions. Engineering trade-offs are made during the design of a lead to optimize one or more performance characteristics: e.g., lead handling, fatigue life, size, and optimized therapy delivery. To assure low defibrillation thresholds, careful attention must be taken during the design process to prevent these trade-offs from hampering the lead's therapy effectiveness. Four basic design rules are described that capture many of the engineering concepts that will enhance a lead's efficacy: (1) minimize electrode pullback, (2) deliver current to the apex, (3) minimize energy loss in the lead, and (4) use large, efficient electrodes. These rules speak to optimizing delivery of current to the heart and efficiency of the lead and electrode interface. When the lead performs its function well, the complete ICD system of the heart, lead, and implantable pulse generator will provide optimal safety margins for device implant and an increased number of patients that can be implanted with a single lead system. PMID- 7777420 TI - Holter functions of the implantable cardioverter defibrillator: what is still missing? AB - The technology of the implantable cardioverter defibrillator (ICD) offers the opportunity to overcome the present limits of the invasive and noninvasive approaches of clinical electrophysiology. The invasive approach enables us to reproduce severe arrhythmias if they are inducible, but does not give information concerning the way they spontaneously arise. The noninvasive approach (Holter) gives this information, but it usually concerns only trivial arrhythmias with different therapeutic targets. One hopes in the future, by means of an important extension to ICD technology, which is not technically possible for the time being, to have access to pertinent information and to a better understanding of the circumstances leading to severe spontaneous arrhythmias, potentially lethal. For the moment, we only have the diagnostic certainty leading to the therapeutic intervention. It is based on an ECG and on the sequence of cardiac cycles preceding the rhythmic controlled accident. These data allow verification of but not explanation of the events. To have a chance to be understood and explained, these "events" must be replaced in the context of the "nonevents." Ideally, one should have all the gross information concerning the last 24 hours and subsequently analyze them. It is already a big step, thanks to the defibrillators the right to therapeutic error has been gained, a unique and fatal accident has been transformed into a repeatable event, and therefore, access is gained to the evolution of the responsible disease. PMID- 7777423 TI - Pacing techniques to terminate ventricular tachycardia. PMID- 7777422 TI - Antiarrhythmic drugs in patients with an automatic implantable defibrillator. PMID- 7777421 TI - Implantable cardioverter defibrillator: effect on survival. PMID- 7777424 TI - Italian multicenter clinical experience with endocardial defibrillation: acute and long-term results in 307 patients. The Italian Endotak Investigator Group. AB - This study presents the acute and long-term results of 307 patients (267 men, mean age 57.5 years, 205 suffering from coronary artery disease, mean left ventricular ejection fraction 33.3%) with malignant ventricular tachyarrhythmias who underwent attempted transvenous ICD implantation with the CPI Endotak lead system in 37 Italian centers. Transvenous ICD implantation was ultimately accomplished in 306 (99.7%) patients. These included 19 subjects with high (< 10 J below output energy of implanted device) defibrillation threshold (DFT) at implant. One hundred sixty-four patients (53%) were implanted with the endocardial lead alone, while 142 also received an SQ patch or SQ array. The mean DFT (not always step-down DFT) at implant was 16.9 +/- 5.7 joules; 15.3 +/- 5.2 joules with biphasic shock and 19.6 +/- 5.4 joules with monophasic shock; P < 0.0001. A significantly higher percentage of patients tested with a biphasic shock could be implanted with adequate safety margin and without an additional SQ patch or SQ array (98% and 81%, respectively). No perioperative deaths occurred. During the mean follow-up of 14.5 +/- 10.2 months, 140 patients (52%) received at least one appropriate shock. An inappropriate shock was observed in 26% of episodes. The 1- and 3-year actuarial incidence of sudden death was 2% and 4%, respectively, and that of total death was 10% and 20%, respectively. A pocket infection requiring ICD explantation occurred in 4 patients (1.4%) and an endocardial lead dislodgment in 11 patients (3.6%). Two patients (0.3%) showed a sensing pin disconnection and six patients (2.3%) had a lead insulation break. The results of this Italian multicenter trial indicate that the CPI Endotak lead system is a simple, safe, and reliable system for endocardial defibrillation. When compared to epicardial leads, it clearly reduces the perioperative mortality and morbidity, while maintaining a similar efficacy in preventing sudden death and terminating ventricular arrhythmias. PMID- 7777425 TI - Future expectations of implantable cardioverter defibrillator therapy. PMID- 7777426 TI - Atrial defibrillator: is it needed? Would society pay for it? PMID- 7777427 TI - Cardioverter defibrillator therapy as a bridge to heart transplantation. AB - The prognosis of patients with severely impaired left ventricular function is poor, with an annual mortality rate of about 50%, and the majority die from sudden cardiac death. Heart transplantation is an accepted therapy for patients with end-stage heart disease; however, about 30% of candidates for transplantation die from sudden cardiac death while on the waiting list. It has been shown that implantable cardioverter defibrillator (ICD) therapy has a low surgical mortality and is highly effective in the prevention of sudden death. Therefore, prophylactic ICD implantation may prevent sudden death in patients with end-stage heart disease while on the waiting list, and it is highly probable that patients with an ICD have a greater chance of survival until a donor heart becomes available. However, this hypothesis still has to be proven by prospective studies. PMID- 7777428 TI - 7th European Symposium on Cardiac Pacing. The official meeting of the Working Groups on Cardiac Pacing and Arrhythmias, European Society of Cardiology. Istanbul, Turkey, June 4-7, 1995. Abstracts. PMID- 7777429 TI - [Repeats of DNA]. PMID- 7777430 TI - [Guanosine tetraphosphate, ppGpp, as a factor of stringent control of DNA replication]. PMID- 7777431 TI - [Nobel prize 1994 -- G proteins]. PMID- 7777432 TI - [Molecular basis of steroid 21-hydroxylase deficiency]. PMID- 7777434 TI - [Neurosteroids--synthesis and metabolism]. PMID- 7777433 TI - [Pioneers in molecular biology: Emil Fischer, Erwin Schrodinger and Oswald T. Avery]. PMID- 7777435 TI - [Prenylation of proteins]. PMID- 7777436 TI - [Cytochrome c conformation and its interactions with cytochrome c oxidase]. PMID- 7777437 TI - [The role of inositol cycle in signal transduction in the cell nucleus]. PMID- 7777438 TI - [Cancer as a disease of the genes]. PMID- 7777439 TI - Peripheral arterial disease. When to consider percutaneous revascularization. AB - Currently, percutaneous revascularization techniques are recommended for peripheral arterial disease only when limiting or disabling symptoms are present. However, the cost of these procedures is less than that of surgery and the risk is much lower. Additional prospective, randomized studies are needed for better definition of the role of percutaneous techniques in clinical practice. In the future, as techniques evolve and outcomes become better defined, this role may be expanded. PMID- 7777440 TI - Adolescent sexual intercourse. Strategies for promoting abstinence in teens. AB - As sex, drugs, and rock 'n' roll have given way to STDs, HIV, and AIDS, adolescent sex has become an increasingly high-risk behavior. Dr Kay strongly believes that primary care physicians can have a prominent role in educating teens and their parents about the consequences of premature sexual activity and in promoting healthy living. In this article, he presents the case against adolescent sexual intercourse and outlines a concrete approach to dealing with adolescent patients at risk and their families. PMID- 7777441 TI - Trichinosis. Still a public health threat. AB - Trichinosis remains a worldwide public health problem, although most US physicians have little or no experience with the disease. A history of exposure to raw or undercooked pork and findings of myopathy, eosinophilia, and periorbital edema are characteristic. The diagnosis can be confirmed with tissue biopsy or serodiagnostic testing. Mild infections respond to limited bed rest and use of analgesics and antipyretics. More severe cases can be treated effectively with corticosteroids and anthelminthics. PMID- 7777442 TI - Vertebral osteomyelitis. How to differentiate it from other causes of back and neck pain. AB - Vertebral osteomyelitis, an uncommon infection, usually presents with the very common symptom of neck or back pain. Awareness of this disorder and its distinctive features aids physicians in prompt ordering of appropriate imaging studies, which usually lead to the diagnosis. Early diagnosis, identification of the infecting microbe, and appropriate antimicrobial therapy are the keys to preventing complications and reducing the need for surgical intervention. PMID- 7777443 TI - Free dinners for seniors who listen to HMO spiel. PMID- 7777445 TI - Borderline personality disorder. Interpersonal and behavioral problems that sabotage treatment success. AB - Patients with borderline personality disorder may be the most psychologically challenging patients a primary care physician ever encounters. Early diagnosis is important to avoid interpersonal enmeshment and personalization in dealings with these patients, who often appear intact initially. The acronym PISIA is useful in recalling the major characteristics of the disorder: psychotic episodes, impulsivity, superficially intact social adaptation, interpersonal-relationship problems, and affective disorders. Specific techniques (eg, setting limits, separating medical and psychological issues, consulting a psychiatrist to determine a psychotropic drug regimen) promote effective treatment of these difficult patients. PMID- 7777444 TI - Myocardial infarction in the 1990s. Complications, prognosis, and changing patterns of management. AB - Arrhythmias are the most common complications of acute myocardial infarction. However, other complications, such as ventricular free-wall rupture, thrombosis in locations other than the primary site of infarction, and thromboembolic strokes, also may occur. In addition, thrombolytic therapy given after infarction may cause intracranial hemorrhage, allergic reactions, and hypotension. To reduce the 1-year mortality rate in patients who survive hospitalization, an effort should be made to detect and treat residual ischemia, ventricular dysfunction, and electrical instability. Follow-up rehabilitation and prevention are essential. In this endeavor, primary care physicians, emergency personnel, specialists, nursing staff, and technicians form an integral team. PMID- 7777446 TI - Physiologic evaluation of bronchial asthma. Why objective testing is essential. AB - Physiologic evaluation of bronchial asthma is extremely valuable. Simple objective measurements of expiratory airflow and lung volume help physicians determine disease status and monitor patient response to therapy. More elaborate measurements of pulmonary function are not commonly needed in primary care practice. The three case studies described in this article show that objective assessment of lung function is critical in effective treatment of asthma. PMID- 7777447 TI - Acute severe asthma. How to recognize and respond to a life-threatening attack. AB - A disturbing increase in mortality from asthma has occurred over the past decade. Asthmatic patients who are over age 55 and have coexisting cardiac or pulmonary disease, those who have a history of mechanical ventilation, and those who require continuous outpatient use of corticosteroids to control symptoms have an increased risk of severe or fatal exacerbations of their disease. Patients hospitalized for severe asthma should receive inhaled beta 2-adrenergic agonists for bronchodilation and intravenous corticosteroids. Patients requiring mechanical ventilation have about a 20% incidence of pneumothorax and an enhanced risk of nosocomial pneumonia, and their mortality rate approaches 20%. Once severe asthma improves, patients must have their outpatient regimen strengthened by the use of oral corticosteroids, inhaled corticosteroids, and/or inhaled cromolyn sodium (Intal). PMID- 7777448 TI - Nocturnal asthma and exercise-induced bronchospasm. Why they occur and how they can be managed. AB - Asthma is increasing in prevalence and morbidity worldwide. Worsening of asthma symptoms during sleep and following exercise is an important component of this morbidity. Better recognition and management of nocturnal asthma and exercise induced broncho-constriction should lead to improved outcomes. Measures to alleviate nocturnal asthma include elimination of exposure to allergens, use of measures to control contributing factors (rhinitis, sinusitis, gastroesophageal reflux, sleep apnea), maximization of the dosage of daytime asthma medications, and appropriately timed use of medications such as a long-acting inhaled beta 2 agonist, a once-daily sustained-release theophylline product, and an oral corticosteroid. Bronchoconstriction after exercise can be decreased by physical conditioning, warm-up exercises, wearing of a face mask in cold weather, postponement of exercise until at least 2 hours after a meal, and pretreatment with an inhaled beta agonist. Pretreatment with inhaled cromolyn sodium (Intal), nedocromil sodium (Tilade), or ipratropium bromide (Atrovent) may be added if necessary. PMID- 7777449 TI - Occupational asthma. Serious consequences for workers and employers. AB - Patients affected by occupational asthma have respiratory symptoms that may persist for months, years, or even life. Hundreds of substances have been implicated in the disease, and the list is expected to grow. The authors discuss management of this sometimes life-threatening condition and emphasize the importance of environmental controls to prevent future cases. PMID- 7777450 TI - XXXVIII Nordic Meeting of Pharmacology and XIII Helsinki University Course in Drug Research. Helsinki, Finland, May 18-20, 1995. Abstracts. PMID- 7777451 TI - [Laser therapy in renal tuberculosis: mechanism of action]. AB - Etiotropic therapy in urinary tuberculosis fails to provide adequate repair. Normalization of renal function requires additional pathogenetic measures, laser treatment, in particular. Experience with laser treatment is now available for respiratory tuberculosis only. Mechanism of action of low-intensity laser radiation in nephrotuberculosis and rationale for its use are described. PMID- 7777452 TI - [Combined use of the Koch tuberculin provocation test and immunological tests in patients with urinary tuberculosis]. AB - The use of provocative Koch test proved most effective in enhancing sensitivity of serological diagnostic tests EIA and IHA with PHA. This contributed to more accurate assessment of the tuberculous process activity in patients with advanced destruction of the kidneys. Quantitation of antituberculous antibodies may serve an additional criterium in evaluation of effectiveness of urological tuberculosis chemotherapy. PMID- 7777453 TI - [Distribution of histocompatibility antigens in patients with pulmonary tuberculosis depending on disease course and immune response pattern]. AB - Genetic relationships with tuberculous process and immunity were investigated within immunogenetic study of 178 patients with active pulmonary tuberculosis. Tuberculosis occurrence seemed to be associated with phenotypical antigen Cw2. Unfavorable outcome of the disease was observed in the presence of HLA A9, A11, B14, B40, B41 antigens. A pronounced specific humoral and cellular responses more frequently arise in carriers of antigens Cw2 and B13, while high proliferative activity of T-cells in carriers of A10, B7 and Cw2. Production of IgA, IgG and IgM is determined by different genetic factors. The results obtained are essential for prognosis of tuberculosis course and choice of individual therapy. PMID- 7777454 TI - [Teaching phthisio-pulmonology in medical college]. PMID- 7777455 TI - [Generation of platelet activating factor by neutrophils in patients with pulmonary tuberculosis]. AB - PAF levels in native blood neutrophils before and after 1-hour incubation with killed BCG culture and in relevant incubation medium were measured in 44 patients with active pulmonary tuberculosis according to rabbit platelet aggregation. A control group consisted of 12 healthy volunteers. Neutrophil PAF concentrations in the patients were 6 times higher than those in the controls and caused a rise in plasma PAF levels. Intracellular PAF content was related to the process characteristics (new-onset tuberculosis, exacerbation, recurrence), intoxication, hemogram shifts and immune status of the patient. In vitro experiments showed that in response to a specific phagocytosis object, generation of PAF in neutrophils and its release into the intercellular space depend on initial PAF levels in native cells. In normal and moderately elevated PAF in native neutrophils contact with killed BCG culture entailed its intracellular content increase, while in initially high intracellular PAF additional stimulation induced primarily its release. PMID- 7777457 TI - [Antibodies to Bacillus megaterium H glycoprotein in patients with lung diseases]. AB - Enzyme immunoassay performed in patients with malignant and benign affections of the lungs determined antibodies (Abs) to glycoprotein isolated from saprophyte microorganism Bacilus megaterium H. In pulmonary tuberculosis and nonspecific pulmonary inflammation the above Abs occurred in patients with fibrous proliferative changes and associated neoplastic conditions. In lung cancer the Abs were detected in well and moderately differentiated tumors. Nondifferentiated and poorly differentiated variants did not exhibit any rise in Abs to glycoprotein. PMID- 7777456 TI - [Development of protective antituberculosis immunity after BCG vaccination in mice with silicon deficiency in water and feed]. AB - An experimental mouse model of normal and deficient content of silicon in the diet in CBA strain has been developed. It is shown that after BCG vaccination silicon deficiency brought about a dramatic decrease of in vitro proliferation of splenic lymphocytes in the presence of mycobacterial antigens, ConA or in the absence of the stimuli. DTH response to tuberculin in silicon deficient mice was also reduced. The level of specific serum IgG did not depend upon silicon content in the diet. The addition of silicon into the diet of silicon-deficient mice beginning from BCG vaccination restored the level of immune reactions. PMID- 7777458 TI - [Basic principles of the diagnosis in pulmonary tuberculosis (lecture)]. PMID- 7777459 TI - [Biological characteristics of M. tuberculosis and difficulties in microbiological diagnosis of tuberculosis]. AB - The paper outlines difficulties in tuberculosis diagnosis and effectiveness of various methods of mycobacteria identification. The latter along with direct and indirect determination of mycobacterial drug resistance require perfection. There is a need in investigation of diagnostic samples from tuberculous and respiratory sarcoidosis patients for mycobacterial granular forms. A multimodality diagnostic approach to examination of clinical material from tuberculous patients is advocated. PMID- 7777461 TI - [Prognostic significance of seroepidemiological check-up in leprosy]. PMID- 7777460 TI - [Cytokines in immunopathogenesis of pulmonary tuberculosis]. AB - Production of IL-1, IL-2, gamma-interferon and PNO was measured in 46 patients with various forms of pulmonary tuberculosis. Cytokins quantitation was conducted biologically, using radioimmunoassay and enzyme immunoassay in supernatants of cellular structures (blood lymphocytes). There were high levels of IL-1 and PNO, reduced production of IL-2 and gamma-IFN by stimulated blood mononuclears. In effective chemotherapy (3-4 months) production of IL-1 tented to a decline, while that of IL-2 and gamma-IFN went up. PMID- 7777462 TI - [Immunomodulating role of endogenous thyroid hormones in mycobacterioses]. AB - Radionuclide tracing in peripheral blood of patients with mycobacterial infections varying in activity (lepromatous lepra, n = 98; pulmonary tuberculosis, n = 51) provided information on lymphocyte proliferative response to PHA, tuberculin, sensitin from lepra mycobacteria, on thyroid hormones concentrations. Endogenic thyroid hormones are shown to have immunomodulating properties closely related to the disease activity. PMID- 7777463 TI - [Affinity isolation of mycobacterial antigens on monoclonal antibodies]. AB - Affinity chromatography on monoclonal antibodies specific to tuberculous mycobacteria was used to isolate mycobacterial antigens from ultrasonic disintegrate M. tuberculosis H37Rv. Disk-electrophoresis on polyacrylamide gel showed purified antigens to consist of polypeptides with molecular mass 16, 19, 32, 60, 27, 70 and 55 kD. The antigens were tested for enzyme immunoassay of antibodies in the sera from patients with infiltrative pulmonary tuberculosis. PMID- 7777464 TI - [Phenotypic and functional analysis of blood lymphocytes and pathological focus in patients with pulmonary tuberculosis]. AB - A subpopulation study of lymphocytes concentrating in cavernous, lymph node tissues and blood from patients with fibrous-cavernous tuberculosis of the lungs showed that in spite of high CD3+ and CD4+ cell levels in the cavern, the response of these cells to mitogens may be weaker than blood lymphocyte response. IL-2 production by cavern lymphocytes varied and was unrelated to proliferative response of these cells to M. tuberculosis antigens. PMID- 7777465 TI - [Protective properties of M. lufu in experimental leprosy]. AB - A protective potential of M. lufu against experimental lepra was studied in mice infected with M. leprae according to Shepard. 5 and 9 months after the inoculation quantitation of the causative agent in the animals' paws indicated a protective action of M. lufu which exceeded that of BCG, M. vaccae and M. leprae. High protective activity of M. lufu is due both to its antigenic composition similarity with M. leprae and influence on immune response regulation. It is suggested to use M. lufu for design of highly effective antilepra vaccine. PMID- 7777466 TI - [Effects of endogenous cortisol on the function of nonspecific T-suppressors and quantitative characteristics of main subpopulations of circulating T-lymphocytes in leprosy]. AB - Serum hydrocortisone levels, cellular immunity and their correlation were studied in 38 patients with lepromatous lepra in regression. 12 of them had exacerbation of specific polyneuritis. The latter condition is accompanied by a rise in hydrocortisone concentrations. Relative number of blood CD8+ lymphocytes correlated positively with hydrocortisone content, whereas the quantity of CD4+ cells correlated negatively. In patients without neurological complications in negative correlation between blood hydrocortisone and lymphocyte glucocorticoid sensitivity there was a positive relationship between nonspecific T-suppressor activity and hydrocortisone levels. The involvement of endogenic hydrocortisone in T-suppressor activity regulation in regressive lepra can help understand the role of endocrine dysfunction and stress in pathogenesis of lepra relapses. PMID- 7777467 TI - [Effectiveness of isoniazid in tuberculosis chemoprophylaxis in children with rising tuberculin sensitivity]. AB - 70 children aged 4-15 with growing tuberculin sensitivity received preventive treatment with isoniazid in children's sanatorium. The drug was taken for 2 or 3 months in a dose 10 mg/kg daily (19 and 51 children, respectively). Preventive isoniazid course proved effective as none of the children treated developed tuberculosis within 3 years. The 3-month course is preferable as it is more potent in relation to tuberculin sensitivity immediately after the treatment termination and 1, 2 years after it. PMID- 7777468 TI - [Effects of diaminodiphenylsulfone and rifampicin on biorhythms of lymphocyte level in intact mice]. AB - Administration of DDS and R alone as well as in combination to CBA mice was studied for effects on blood lymphocyte biorhythms. These drugs were found to affect circadian rhythms of lymphocyte number. The changes depended on the season and time of administration. Allowances for the above changes help correct asynchronism thus improving the response rate. PMID- 7777469 TI - [Broncholytic activity of dose-adjusted aerosols in active respiratory tuberculosis]. PMID- 7777471 TI - Noncalcific cusp thickening in Ionescu-Shiley cardiac valvular bioprostheses. AB - This study was undertaken to examine the morphological basis for noncalcific cusp thickening in 20 standard-profile Ionescu-Shiley bovine pericardial cardiac valvular bioprostheses (16 aortic, four mitral) with primary valve failure due to cusp tears. The patients included 17 males and three females, with a mean age of 52.0 years; their valves had been implanted for a mean of 105.8 months. All cases had variable degrees of "plasma insudation" without correlation to identifiable patient parameters. This was accentuated in individual valves in the cusp with the most extensive tears. In addition, the three valves with the thickest cusps were grossly distorted by massive deposits of amyloid (identified as AL-amyloid in two index cases studied). Two other valves had incidental amyloid deposits, identifiable only by electron microscopy. Amyloid involvement of pericardial bioprostheses has not been previously reported. The literature pertaining to amyloid involvement and plasma insudation of bioprostheses is reviewed. PMID- 7777472 TI - Fine needle aspiration biopsy of proliferative breast disease. AB - Proliferative breast disease (PBD) is a well-recognized histologic entity that has received increasing attention in the cytologic literature. We have attempted to prospectively identify and subclassify PBD by fine needle aspiration biopsy since 1987 using criteria we developed through our experience. Over 2800 breast FNABs were performed on breast lesions from 1987 to mid-1992; 257 were cytologically diagnosed as PBD with or without atypia. Eighty-four were significantly worrisome clinically to warrant surgical excision. Forty of these were designated PBD without atypia by cytology; 23 (58%) were in agreement with histology; three (8%) were PBD with atypia by histology; five (13%) were cancers; and nine (22%) were nonproliferative. Forty-four cases were designated PBD with atypia; 24 (55%) were in agreement with the histologic diagnosis; 12 (27%) proved to be PBD without atypia; six (13%) were carcinoma; and two (5%) were nonproliferative. After 1991 we employed stricter criteria for PBD, improving on the results from 1991-1992. During this period, there were 53 diagnoses of PBD with or without atypia and 34 were excised. Nine of the 10 (90%) aspirates designated as PBD without atypia were in agreement with histologic findings. The other case was nonproliferative. Fifteen of the 24 cases diagnosed as PBD with atypia were in concordance with histologic findings (63%), one was nonproliferative, seven were PBD without atypia (29%), and one (4%) proved to be carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777470 TI - [Clinical aspects and course of extrapulmonary sarcoidosis]. AB - Follow-up results (3-15 years) are available for 95 patients with extrapulmonary sarcoidosis. The disease presented with multiple lesions and recurrent course. Peripheral lymph nodes were the most frequent location. Severe course was more typical for sarcoidosis of the nervous system, liver, and the kidneys. Combined treatment (corticosteroids, antioxidants, immunocorrection) proved an effective modality. PMID- 7777473 TI - Diagnosis of chronic lung transplant rejection by transbronchial biopsy. AB - Chronic rejection in the form of obliterative bronchiolitis (OB) associated with chronic inflammation and fibrosis of bronchi (CIB) is a significant cause of morbidity and mortality in long-term heart-lung and single-lung transplant recipients. To determine the utility of transbronchial biopsy in diagnosing chronic rejection, we reviewed 24 transbronchial biopsies (TBBs) performed at the time of, or subsequent to, a clinical diagnosis of OB of chronic rejection in eight heart-lung and single-lung transplant recipients at the Methodist Hospital, Houston, Texas. These were compared with 36 randomly selected control TBBs from 14 patients without a clinical or histopathologic diagnosis of OB of chronic rejection at any time in their course. In the former group of TBBs, nine (38%) were diagnostic of OB and seven (29%) showed CIB suspicious for chronic rejection. TBBs diagnosed as negative had significantly fewer samples of tissue (1.0 versus > 3) and significantly smaller size of tissue (1.44 mm versus > 4.5 mm) than did TBBs in the OB or CIB categories. When strict criteria were used, no false diagnoses of OB of chronic rejection were made on control TBBs. However, OB associated with bronchiolitis obliterans organizing pneumonia of viral pneumonitis was present in three (8%) and CIB in 15 (42%) of control TBB associated with acute rejection and infection. This finding emphasizes the nonspecificity of CIB. We conclude that TBB is potentially useful in diagnosing OB of chronic rejection in some cases and in suggesting chronic rejection in other cases. Inadequate sampling by the bronchoscopist was the major reason for a negative biopsy. PMID- 7777474 TI - AgNORs predictive value of prognosis in non-Hodgkin's lymphoma according to the Kiel classification. AB - Application of the colloidal silver method for demonstration of argyrophilic proteins of nucleolar organizer regions (AgNORs) in histological sections of non Hodgkin's lymphomas (NHLs) has been shown to be a helpful method for the discrimination of high- and low-grade NHL. In this study correlation between the mean number of AgNORs and other morphological and clinical parameters with survival in 58 patients with NHL, classified according to the Kiel classification, was investigated. It was shown that the mean number of AgNORs differed between the low- and high-grade group of NHLs (P < 0.001), as did survival (P < 0.0001). The mean number of AgNORs was also highly significant when describing actuarial survival. The value of 2.9 NORs per nuclei was the cut-point for separating the whole group into two subgroups, which differed the most when related to survival of patients with NHL. PMID- 7777475 TI - bcl-2 protein expression in melanocytic neoplasms of the skin. AB - Since the discovery of bcl-2 proto-oncogene in follicular lymphomas, the protein product has been detected in a variety of normal tissues including skin, where it is expressed in basal keratinocytes. Recent studies indicate that bcl-2 protein is detected in nonlymphoid malignancies such as neuroblastoma and carcinomas of the lung and prostate. This study investigates the presence of bcl-2 protein in benign and malignant melanocytic neoplasms of the skin. Immunohistochemical analysis of bcl-2 protein expression was performed on 39 nevi and 60 malignant melanomas, including 21 metastases. There was diffuse strong immunopositivity for bcl-2 protein in 100% of nevi and 65% (43/60) of primary and metastatic melanomas. bcl-2 protein was diffusely expressed in 67% (30/39) of primary melanomas and 54% (11/21) of metastases. Although bcl-2 immunoreactivity was observed in all levels of primary cutaneous malignant melanomas, in 43% (9/21) of deep melanomas (Clark level > or = III), and 100% (7/7) of thick tumors (thickness > or = 4.00 mm), there was focal loss of immunoreactivity. Metastatic melanomas showed focal loss of bcl-2 expression in 10% (2/21) of cases and total loss of bcl-2 protein in 39% (8/21). We conclude from our results that bcl-2 protein is expressed by benign and malignant melanocytic tumors of the skin, but there is loss of bcl-2 protein expression with increasing tumor progression. PMID- 7777476 TI - Fibroma and giant cell tumor of tendon sheath: a comparative histological and immunohistological study. AB - Giant cell tumor of tendon sheath (GCTTS; "nodular tenosynovitis") and fibroma of tendon sheath (FTS) have traditionally been considered to be two points in a single neoplastic continuum. However, no systematic studies have addressed this concept directly to date. To more clearly define their relationship to one another, we studied five FTSs and seven typical GCTTSs by light microscopy and paraffin section immunohistochemistry. Tissue samples were stained for vimentin, desmin, smooth muscle actin (SMA), S100 protein, leukocyte common antigen (CD45), CD68 antigen (KP1), HAM56 antigen, alpha-1-antichymotrypsin (AACT), and MAC387 antigen. These reagents were chosen to address proposed "fibrohistiocytic" and myofibroblastic lineages for the two lesions. All tumors had a lobular appearance. GCTTS was more cellular than FTS; it contained conspicuous numbers of osteoclast-like cells, and the stroma was not extensively hyalinized. In contrast, FTS was matrix-rich, often with extensive stromal sclerosis, and contained only rare giant cells. Immunophenotyping of GCTTS showed that both the spindle cell and giant cell components were positive for vimentin, LCA, CD68, HAM56, AACT, and MAC387, suggesting monocyte-macrophage-like features. Limited reactivity for desmin and SMA also implied conjoint myofibroblastic differentiation. On the other hand, FTS showed focal staining with HAM56 (all cases) and for CD68 (one case); staining for vimentin and SMA was uniformly intense and diffuse. Based on these results, we conclude that GCTTS and FTS both exhibit varying degrees of monocyte-macrophage-like and myofibroblastic differentiation. The predominance of macrophage-related determinants in GCTTS and myofibroblastic markers in FTS supports the premise that these lesions represent phenotypic extremes of a single clinicopathologic entity. PMID- 7777477 TI - Biologic markers of invasive pituitary adenomas involving the sphenoid sinus. AB - The biologic behavior of invasive pituitary adenomas is poorly understood and appears to be intermediate between intrasellar adenomas and pituitary carcinoma. Utilizing immunohistochemistry on tissue sections, we examined 10 invasive pituitary adenomas involving the sphenoid sinus with a panel of cellular and molecular markers and compared the results with 10 noninvasive pituitary adenomas and five normal pituitary glands. The panel included Ki-67 and PCNA (proliferation cell nuclear antigen), cell proliferation indicators; interleukin 6 (IL-6), a multifunctional cytokine; heat shock protein 27 (HSP 27), a stress response protein; and p53, a tumor suppressor gene product. We found strong expression of IL-6 in normal pituitary glands, 20% of noninvasive and 50% of invasive adenomas. HSP 27 was absent in normal glands and present in 10% of noninvasive and 50% of invasive adenomas. The Ki-67 and PCNA proliferation index was above normal but was essentially the same in the two groups. p53 was not detected in any specimens. We propose that both IL-6 and HSP 27 may be markers of biologic aggression in pituitary adenomas. PMID- 7777478 TI - Alveolar cell hyperplasia in association with adenocarcinoma of lung. AB - We studied 41 patients, 22 men and 19 women, with surgically resected adenocarcinoma (AD) of the lung, to determine the frequencies of associated alveolar cell hyperplasia (ACH) and atypical alveolar cell hyperplasia (AACH), and to define the immunohistochemical profiles (IHP) of the AD, ACH, and AACH. The criteria used to look for ACH included a single row of cuboidal cells along alveolar walls, cell morphology distinct from bronchiolar epithelium, and the absence of chronic inflammation. AACH was considered whenever nuclear size was double the size of neighboring ACH and/or in cases with marked nuclear irregularity or hyperchromatism. ACH was identified in 24 of the 41 cases of AD. AACH was further demonstrated in six of the 24 cases of ACH. Twenty-three of the 24 cases of ACH were suitable for IHP. The tumors yielded positive results in 23/23, 22/23, 17/23, 22/23, and 18/23 cases when stained with Cam 5.2, AE1/AE3, Leu M-1, CEA, and B72.3, respectively. ACH reacted positively in 17/23, 17/23, 0/23, 4/22, and 1/23 cases stained with Cam 5.2, AE1/AE3, Leu M-1, CEA, and B72.3, respectively. AACH reacted positively in 6/6, 6/6, 0/6, 1/6, and 0/6 cases stained with Cam 5.2, AE1/AE3, Leu M-1, CEA, and B72.3, respectively. These findings suggest that ACH and AACH are common features found in 24 and six of the 41 cases of AD, respectively. The significance of this finding is not known, but it is possible that ACH/AACH may represent precursor changes similar to the bronchial epithelial dysplasia described in squamous cell carcinoma of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777479 TI - p53 gene mutations in human urothelial carcinomas: analysis by immunohistochemistry and single-strand conformation polymorphism. AB - We examined 60 cases of human urothelial carcinomas (27 superficial and 33 deeply invasive) for the frequency of p53 gene mutations. Forty-two cases were analyzed by both the immunohistochemical and the single-strand conformation polymorphism (SSCP) methods, and the remaining 18 cases were assayed by SSCP alone. For the latter assay, exons 4 to 8 were amplified by polymerase chain reaction, and the amplified nucleotides were analyzed for the evidence of mutations by gel electrophoresis. When mobility shift was observed, direct nucleotide sequencing was performed to determine mutation sequence. Three superficial and eight deeply invasive carcinomas demonstrated evidence of mutations. Mutations involved various codons randomly. The fact that all tumors with mutations of the p53 gene except for one were of high nuclear grade (grade III) suggests that p53 mutation is associated with the progression of bladder cancers. Our results indicate that SSCP is a sensitive screening assay for detecting gene mutations. Immunohistochemical analysis is also a sensitive method but may yield false positive as well as false negative results. PMID- 7777480 TI - Influence of formalin fixation time and tissue processing method on immunoreactivity of monoclonal antibody PC10 for proliferating cell nuclear antigen. AB - Proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase delta, has recently been proposed as a marker of proliferation that is detectable in formalin-fixed paraffin-embedded tissue. Fixation time has been known to influence protein immunoreactivity and therefore can significantly influence the results of a quantitative immunohistochemical assay. In this study, we investigate the relationship between formalin fixation time and immunoreactivity for PCNA in paraffin-embedded sections and examine the effect of postfixation tissue treatment with modified Bouin's solution. Samples of small and large intestine from two freshly sacrificed rats were fixed in 10% buffered formalin for 6, 30, 54, 174, 340, and 508 h. Standard histological processing was performed on paired specimens whose treatment differed only by predehydration immersion in a picric acid and mercuric chloride-containing solution. Paraffin sections were reacted with monoclonal antibody PC10 in a standard immunoperoxidase assay. Staining intensity for PCNA was scored on a scale of 0 to 10, and the mean number of PCNA-positive cells per crypt (10 crypts counted) was determined. No difference between animals was found. PCNA immunoreactivity was maximal in specimens fixed for 6 to 30 h, exponentially declining with longer fixation time. The rate of decline was mitigated in the treated sections. Fixation-time dependence of PCNA immunoreactivity has immediate implications for intra- and interlaboratory comparisons, especially in experimental studies in which specimens can be stored in formalin for variable times followed by batch processing. With regard to surgical pathology specimens, this study suggests that sample comparisons are valid, since routine fixation time is within the optimal rage for PCNA immunodetection. PMID- 7777481 TI - Interphase cytogenetic analysis of single cell suspensions prepared from previously formalin-fixed and paraffin-embedded tissues. AB - Fluorescence in situ hybridization (FISH) provides a rapid and accurate method for the detection of chromosomal aneuploidy. We have developed a technique for the use of FISH on single cell suspensions produced from either formalin-fixed or paraffin-embedded tissues. Preparation of such tissues involves sequential rehydration, enzymatic digestion to release single nuclei, and hybridization with a fluorescently labeled chromosome-specific centromeric probe. In a clinical setting formalin-fixed tissue from many tissue types is readily available for additional retrospective study. FISH on formalin-fixed tissues is especially beneficial in follow-up studies of cases involving termination after prenatal diagnosis or patients with a malignant disease where previous routine cytogenetics established the chromosomal aneuploidy. The use of this technique eliminates the biases of cytogenetic analysis due to clonal selection in tissue culture, the low number of cells analyzed, and the restriction to only dividing cell populations. We have demonstrated that this application of interphase cytogenetics to the study of various formalin-fixed tissues is amenable to the detection of chromosomal aneuploidies and has specific advantages over cytogenetic analysis. PMID- 7777482 TI - Nuclear morphometry in breast cancer: the influence of sampling rules and freezing of samples. AB - We studied nuclear morphometry of human breast cancer with special emphasis on two sources of variation: freezing prior to fixation and selection of measured objects on the basis of different sampling rules. Samples of 147 histologically verified invasive breast cancer cases were examined with a computer-based image overlay drawing system. Thirty-eight of the 147 samples of tissue frozen before embedding in paraffin were analyzed separately. Among the latter we found shrinkage of 35% and 46% (depending on the sampling rule) of the nuclear profile area as compared with samples not frozen before the standard tissue processing. These findings confirm that nuclear morphometry results from frozen and unfrozen tissue are not comparable. Frozen tissue later embedded in paraffin should not be used with prognostication models based on traditionally fixed tissue. In morphometry we applied two sampling rules that differed in the criteria used for selecting nuclei for measurement. We registered a significant difference in nuclear size and in the variation of nuclear size between the two sampling methods. Of the morphometric features studied, nuclear area was affected most. Finally, we examined the two sampling rules in light of the established prognosticators in breast cancer: tumor size, axillary lymph node status, and the Multivariate Prognostic Index (MPI). The two sampling rules resulted in different distributions of morphometric results in the prognostic groups. Our findings emphasize the significance of the sources of variation in nuclear morphometry. They also stress the need for well-standardized morphometric methods in predicting the outcome of breast cancer. PMID- 7777483 TI - Gastrointestinal stromal tumor: evidence for a smooth-muscle origin. AB - A gastrointestinal stromal tumor, arising from the rectal ampulla of a 63-yr-old man, was investigated using conventional techniques as well as Western blot analysis of its cytoskeleton proteins. The expression of desmin, muscle-specific actins, vimentin, S-100 protein, chromogranin, neuron-specific enolase, and keratins was studied using the avidin-biotin technique. The tumor cells showed a positive reaction only to antivimentin antibody. Ultrastructural analysis failed to provide conclusive evidence for neural or muscular origin of the tumor. Western blot analysis of the tumor whole-protein extract allowed identification of the presence of gamma-smooth-muscle actin, thus suggesting an enteric smooth muscle origin of the tumor. This result seems partially to support a parenchymal smooth-muscle origin for S-100 protein and desmin-negative gastrointestinal tumors. PMID- 7777484 TI - The pathology of AIDS. PMID- 7777485 TI - Crystallization, molecular replacement solution, and refinement of tetrameric beta-amylase from sweet potato. AB - Sweet potato beta-amylase is a tetramer of identical subunits, which are arranged to exhibit 222 molecular symmetry. Its subunit consists of 498 amino acid residues (Mr 55,880). It has been crystallized at room temperature using polyethylene glycol 1500 as precipitant. The crystals, growing to dimensions of 0.4 mm x 0.4 mm x 1.0 mm within 2 weeks, belong to the tetragonal space group P4(2)2(1)2 with unit cell dimensions of a = b = 129.63 A and c = 68.42 A. The asymmetric unit contains 1 subunit of beta-amylase, with a crystal volume per protein mass (VM) of 2.57 A3/Da and a solvent content of 52% by volume. The three dimensional structure of the tetrameric beta-amylase from sweet potato has been determined by molecular replacement methods using the monomeric structure of soybean enzyme as the starting model. The refined subunit model contains 3,863 nonhydrogen protein atoms (488 amino acid residues) and 319 water oxygen atoms. The current R-value is 20.3% for data in the resolution range of 8-2.3 A (with 2 sigma cut-off) with good stereochemistry. The subunit structure of sweet potato beta-amylase (crystallized in the absence of alpha-cyclodextrin) is very similar to that of soybean beta-amylase (complexed with alpha-cyclodextrin). The root mean-square (RMS) difference for 487 equivalent C alpha atoms of the two beta amylases is 0.96 A. Each subunit of sweet potato beta-amylase is composed of a large (alpha/beta)8 core domain, a small one made up of three long loops [L3 (residues 91-150), L4 (residues 183-258), and L5 (residues 300-327)], and a long C-terminal loop formed by residues 445-493. Conserved Glu 187, believed to play an important role in catalysis, is located at the cleft between the (alpha/beta)8 barrel core and a small domain made up of three long loops (L3, L4, and L5). Conserved Cys 96, important in the inactivation of enzyme activity by sulfhydryl reagents, is located at the entrance of the (alpha/beta)8 barrel. PMID- 7777487 TI - A new protein folding recognition potential function. AB - On the study of protein inverse folding problem, one goal is to find simple and efficient potential to evaluate the compatibility between structure and a given sequence. We present here a novo empirical mean force potential to address the importance of electrostatic interactions in protein inverse folding study. It is based on protein main chain polar fraction and constructed in a way similar with Sippl's from a database of 64 known independent three-dimensional protein structures. This potential was applied to recognize the protein native conformations among a conformation pool. Calculated results show that this potential is powerful in picking out native conformations, in addition it can also find structure similarity between proteins with low sequence similarity. The success of this new potential clearly shows the importance of electrostatic factors in protein inverse folding studies. PMID- 7777486 TI - A vector projection method for predicting the specificity of GalNAc-transferase. AB - The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminytransferase (GalNAc-transferase) is consistent with the existence of an extended site composed of nine subsites, denoted by P4, P3, P2, P1, P0, P1', P2', P3', P4', where the acceptor at P0 is being either Ser or Thr. To predict whether a peptide will react with the enzyme to form a Ser- or Thr-conjugated glycopeptide, a vector projection method is proposed which uses a training set of amino acid sequences surrounding 90 Ser and 106 Thr O-glycosylation sites extracted from the National Biomedical Research Foundation Protein Database. The model postulates independent interactions of the 9 amino acid moieties with their respective binding sites. The high ratio of correct predictions vs. total predictions for the data in both the training and the testing sets indicates that the method is self-consistent and efficient. It provides a rapid means for predicting O glycosylation and designing effective inhibitors of GalNAc-transferase. PMID- 7777488 TI - Affinities of phosphorylated substrates for the E. coli tryptophan synthase alpha subunit: roles of Ser-235 and helix-8' dipole. AB - The roles of Ser-235 and helix-8' (residues 235-242) in the functional binding and turnover of phosphorylated substrates by the alpha-subunit of the E. coli tryptophan synthase (TSase) alpha 2 beta 2-holoenzyme complex are examined. Previous crystallographic analyses indicated that this region was one of several near the phosphate moiety of the physiological substrate, indole-3-glycerol phosphate (IGP). The peptidyl amido group of Ser-235 was suggested to H-bond to the phosphate group; a helix macrodipole binding role was suggested for helix-8'. The activities and substrate Kms of mutant alpha-subunits altered in this region by site-specific mutagenesis are reported here. Substitutions at Ser-235 by an acidic (glutamic acid, mutant SE235), basic (lysine, mutant SK235), or a non peptidyl amido-containing residue (proline, mutant SP235) exhibit 40- to 180-fold Km increases for IGP and D-glyceraldehyde-3-phosphate; no Km defects for indole were observed. kcat values for SP235, SE235, and SK235 are 100, 70, and 40%, respectively, of the wild-type value. Steric considerations may explain the results with the SE235 and SK235 mutant alpha-subunits; however, the SP235 results are consistent with the suggested phosphate binding role for the Ser-235 peptidyl amido group during catalysis, A helix-8' dipole role was explored following proline substitutions separately at the first six (of eight) residues. Proline substitutions at positions-1 through -4 in helix-8' have normal indole Kms and catalytic activities in all four TSase reactions, suggesting no major global structural changes in these proteins. By these criteria, substitutions at positions-5 and -6 lead to significant structural alterations. Km increases for phosphorylated substrates are substantial (up to 40-fold) and are dependent upon the presence of L-serine at the beta-subunit active site. In the absence of L serine, substitution only at the first position results in binding defects; in the presence of L-serine, substitutions at the first, second and third positions, show binding defects of decreasing magnitude, sequentially. Substitutions at the fourth and fifth position have no effect on substrate binding. It is suggested that during catalysis a helix dipole effect on binding may be exerted but only via intersubunit-induced conformational changes due to ligand (L-serine) binding to the beta-subunit. PMID- 7777489 TI - A model of the complex between interleukin-4 and its receptors. AB - A three-dimensional model of interleukin-4 (IL-4) bound to one molecule each of the high- and low-affinity receptors (IL-4R and IL-2R gamma) was built, using the crystal structure of the complex of human growth hormone (HGH) with its receptor (HGHR) as a starting model. The modeling of IL-4 with its receptors was based on the conservation of the sequences and on the predicted structural organization for cytokine receptors, and assuming that the binding mode of the ligands would be similar. Analysis of the interface between IL-4 and both receptor molecules was carried out to reveal which residues are important for complex formation. The modeling procedures showed that there were no major problems in maintaining a reasonable fit of IL-4 with the two receptor molecules, in a manner analogous to the complex of HGH-HGHR. Many of the residues that appear by modeling to be important for binding between IL-4 and the receptors have been previously implicated in that role by different methods. A striking motif of aromatic and positively charged residues on the surface of the C-terminal domains of the receptors is highly conserved in the structure of HGH-HGHR and in the models of IL-4 complexed with its receptors. PMID- 7777490 TI - Structural studies of a synthetic peptide derived from the carboxyl-terminal domain of RNA polymerase II. AB - The conformation of the repeating heptapeptide unit of the carboxyl-terminal domain of RNA Polymerase II, Y1S2P3T4S5P6S7 has been examined using nuclear magnetic resonance spectroscopy and circular dichroism. Nuclear Overhauser effects and CD spectra for the synthetic 56-residue peptide H2N-(S2P3T4S5P6S7Y1)8 COOH in water indicate that the peptide is largely unordered. A small population of folded molecules is observed to contain beta-turns located at Ser2-Pro3-Thr4 Ser5 (SPTS) and Ser5-Pro6-Ser7-Tyr1 (SPSY). CD and NMR results in 90% TFE also indicate an equilibrium population of structures, but the fraction of turns is higher. Similarities of nuclear Overhauser effects in water and in 90% TFE suggest that the structures in TFE are biologically relevant. Based on these observations, the average structure of a single conformer of the heptapeptide repeat in 90% TFE was obtained by a distance geometry-simulated annealing method, using distance restraints extracted from nuclear Overhauser data. NMR spectra of the 56-mer show signals corresponding to only one repeat indicating that each repeat is in an identical environment. Thus it is possible to obtain an average structure of the heptapeptide repeat from NOE data on the 56-mer. Twenty-seven final structures were calculated and the root mean square deviations between the 27 structures and the mean coordinates was 1.52 A for the backbone and 2.2 A for all nonhydrogen atoms. The heptapeptide repeat consists of two overlapping beta turns which are potentially stabilized by hydrogen bonds. The hydroxyl side chains of Ser2, Ser5, Thr4, and Ser7 all appear to be equally exposed for potential phosphorylation. The tyrosyl side chain of each repeat is folded inwards to the backbone and can potentially hydrogen bond to the carbonyl oxygen of the tyrosine in the preceding repeat. Interation of the average structure of the heptapeptide repeat results in a model of the carboxyl-terminal domain with a regular but unusual secondary structure consisting of a series of staggered beta turns. PMID- 7777491 TI - Crystallization and preliminary X-ray diffraction studies of an a1/alpha 2/DNA ternary complex. AB - Crystals have been obtained of a ternary complex containing the yeast a1/alpha 2 homeodomain heterodimer bound to a 21-base pair DNA site containing two 5' overhanging bases at each end. The crystals are grown from cobaltic hexamine and form in space group P6(1) or P6(5) with a = b = 133 A, c = 45.4 A. Crystals that are flash-frozen at -179 degrees C diffract to 2.7 A along the c-axis and to 2.4 A in perpendicular directions. The crystals contain one protein-DNA complex in the crystallographic asymmetric unit. PMID- 7777492 TI - Three-dimensional structure prediction of the NAD binding site of proton-pumping transhydrogenase from Escherichia coli. AB - A three-dimensional structure of the NAD site of Escherichia coli transhydrogenase has been predicted. The model is based on analysis of conserved residues among the transhydrogenases from five different sources, homologies with enzymes using NAD as cofactors or substrates, hydrophilicity profiles, and secondary structure predictions. The present model supports the hypothesis that there is one binding site, located relatively close to the N-terminus of the alpha-subunit. The proposed structure spans residues alpha 145 to alpha 287, and it includes five beta-strands and five alpha-helices oriented in a typical open twisted alpha/beta conformation. The amino acid sequence following the GXGXXG dinucleotide binding consensus sequence (residues alpha 172 to alpha 177) correlates exactly to a typical fingerprint region for ADP binding beta alpha beta folds in dinucleotide binding enzymes. In the model, aspartic acid alpha 195 forms hydrogen bonds to one or both hydroxyl groups on the adenosine ribose sugar moiety. Threonine alpha 196 and alanine alpha 256, located at the end of beta B and beta D, respectively, create a hydrophobic sandwich with the adenine part of NAD buried inside. The nicotinamide part is located in a hydrophobic cleft between alpha A and beta E. Mutagenesis work has been carried out in order to test the predicted model and to determine whether residues within this domain are important for proton pumping directly. All data support the predicted structure, and no residue crucial for proton pumping was detected. Since no three dimensional structure of transhydrogenase has been solved, a well based tertiary structure prediction is of great value for further experimental design in trying to elucidate the mechanism of the energy-linked proton pump. PMID- 7777493 TI - Rethinking cell structure. AB - Cell structure, emerging from behind the veil of conventional electron microscopy, appears far more complex than formerly realized. The standard plastic embedded, ultrathin section can image only what is on the section surface and masks the elaborate networks of the cytoplasm and nucleus. Embedment-free electron microscopy gives clear, high-contrast micrographs of cell structure when combined with removal of obscuring material such as soluble proteins. The resinless ultrathin section is the technique of choice; it is simple and inexpensive, and it uses ordinary electron microscopes. The resulting pictures reveal a world of complex cell structure and function. These images necessarily change our conception of the cytoskeleton, nuclear matrix, mitosis, and the relation of membranes to cytostructure. PMID- 7777495 TI - Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension. AB - Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These diseases are primarily determined by defects in single genes, and their modes of inheritance are well understood. When the disease under study has a complex etiology with multiple genetic and environmental components, the generation of animal models becomes more difficult but no less valuable. The problems associated with dissecting out the individual genetic factors also increases substantially and the distinction between causation and correlation is often difficult. To prove causation in a complex system requires rigorous adherence to the principle that the experiments must allow detection of the effects of changing only a single variable at one time. Gene targeting experiments, when properly designed, can test the effects of a precise genetic change completely free from the effects of differences in any other genes (linked or unlinked to the test gene). They therefore allow proofs of causation. PMID- 7777494 TI - The causes and prevention of cancer. AB - Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer. Other factors include avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. A substantial reduction in breast cancer is likely to require modification of sex hormone levels, and development of practical methods for doing so is a high research priority. Resolution of the potential protective roles of specific antioxidants and other constituents of fruits and vegetables deserves major attention. Mechanistic studies of carcinogenesis indicate an important role of endogenous oxidative damage to DNA that is balanced by elaborate defense and repair processes. Also key is the rate of cell division, which is influenced by hormones, growth, cytotoxicity, and inflammation, as this determines the probability of converting DNA lesions to mutations. These mechanisms may underlie many epidemiologic observations. PMID- 7777496 TI - Symbiotic induction of a MADS-box gene during development of alfalfa root nodules. AB - In response to infection by Rhizobium, highly differentiated organs called nodules form on legume roots. Within these organs, the symbiotic association between the host plant and bacteria is established. A putative plant transcription factor, NMH7, has been identified in alfalfa root nodules. nmh7 contains a MADS-box DNA-binding region and shows homology to flower homeotic genes. This gene is a member of a multigene family in alfalfa and was identified on the basis of nucleic acid homology to plant regulatory protein genes (MADS-box containing genes) from Antirrhinum and Arabidopsis. RNA analysis and in situ hybridization showed that expression of this class of regulatory genes is limited to the infected cells of alfalfa root nodules and is likely to be involved in the signal transduction pathway initiated by the bacterial symbiont, Rhizobium meliloti. The expression of nmh7 in a root-derived organ is unusual for this class of regulatory genes. PMID- 7777497 TI - Emergence of a new epidemic/epizootic Venezuelan equine encephalitis virus in South America. AB - One of the most important questions in arbovirology concerns the origin of epidemic Venezuelan equine encephalitis (VEE) viruses; these viruses caused periodic, extensive epidemics/epizootics in the Americas from 1938-1973 (reaching the United States in 1971) but had recently been presumed extinct. We have documented the 1992 emergence of a new epidemic/epizootic VEE virus in Venezuela. Phylogenetic analysis of strains isolated during two outbreaks indicated that the new epidemic/epizootic virus(es) evolved recently from an enzootic VEE virus in northern South America. These results suggest continued emergence of epizootic VEE viruses; surveillance of enzootic viruses and routine vaccination of equines should therefore be resumed. PMID- 7777498 TI - Structural variety of arginine-rich RNA-binding peptides. AB - Arginine-rich domains are used by a variety of RNA-binding proteins to recognize specific RNA hairpins. It has been shown previously that a 17-aa arginine-rich peptide from the human immunodeficiency virus Rev protein binds specifically to its RNA site when the peptide is in an alpha-helical conformation. Here we show that related peptides from splicing factors, viral coat proteins, and bacteriophage antiterminators (the N proteins) also have propensities to form alpha-helices and that the N peptides require helical conformations to bind to their cognate RNAs. In contrast, introducing proline mutations into the arginine rich domain of the human immunodeficiency virus Tat protein abolishes its potential to form an alpha-helix but does not affect RNA-binding affinity in vitro or in vivo. Based on results from several peptide-RNA model systems, we suggest that helical peptides may be used to recognize RNA structures having particularly wide major grooves, such as those found near loops or large bulges, and that nonhelical or extended peptides may be used to recognize less accessible grooves. PMID- 7777499 TI - Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2. AB - BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210BCR-ABL and p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively. Their role in the etiology of human leukemia remains to be defined. Transformed murine hematopoietic cells can be used as a model of BCR ABL function since these cells can be made growth factor independent and tumorigenic by the action of the BCR-ABL oncogene. We show that the BCR-ABL oncogenes prevent apoptotic death in these cells by inducing a Bcl-2 expression pathway. Furthermore, BCR-ABL-expressing cells revert to factor dependence and nontumorigenicity after Bcl-2 expression is suppressed. These results help to explain the ability of BCR-ABL oncogenes to synergize with c-myc in cell transformation. PMID- 7777501 TI - Direct measurement of hydrogen bonding in DNA nucleotide bases by atomic force microscopy. AB - We have used self-assembled purines and pyrimidines on planar gold surfaces and on gold-coated atomic force microscope (AFM) tips to directly probe intermolecular hydrogen bonds. Electron spectroscopy for chemical analysis (ESCA) and thermal programmed desorption (TPD) measurements of the molecular layers suggested monolayer coverage and a desorption energy of about 25 kcal/mol. Experiments were performed under water, with all four DNA bases immobilized on AFM tips and flat surfaces. Directional hydrogen-bonding interaction between the tip molecules and the surface molecules could be measured only when opposite base pair coatings were used. The directional interactions were inhibited by excess nucleotide base in solution. Nondirectional van der Waals forces were present in all other cases. Forces as low as two interacting base pairs have been measured. With coated AFM tips, surface chemistry-sensitive recognition atomic force microscopy can be performed. PMID- 7777502 TI - Efficient high-resolution genetic mapping of mouse interspersed repetitive sequence PCR products, toward integrated genetic and physical mapping of the mouse genome. AB - The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped > 450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries. PMID- 7777500 TI - Distinct regions of c-Mpl cytoplasmic domain are coupled to the JAK-STAT signal transduction pathway and Shc phosphorylation. AB - c-Mpl, a member of the hematopoietic cytokine receptor family, is the receptor for thrombopoietin. To investigate signal transduction by c-Mpl, a chimeric receptor, composed of the extracellular domain of human growth hormone receptor and the intracellular domain of c-Mpl, was introduced into the interleukin 3 dependent cell line Ba/F3. In response to growth hormone, this chimeric receptor induced growth in the absence of interleukin 3. Deletion analysis of the 123 amino acid intracellular domain indicated that the elements responsible for this effect are present within the 63 amino acids proximal to the transmembrane domain. Mutation of the recently described box 1 motif abrogated the proliferative response. Tyrosine phosphorylation of the tyrosine kinase JAK-2 and activation of STAT proteins were dependent on box 1 and sequences within 63 amino acids of the plasma membrane. STAT proteins activated by thrombopoietin in a megakaryocytic cell line were purified and shown to be STAT1 and STAT3. A separate region located at the C terminus of the c-Mpl intracellular domain was found to be required for induction of Shc phosphorylation and c-fos mRNA accumulation, suggesting involvement of the Ras signal transduction pathway. Thus, at least two distinct regions are involved in signal transduction by the c Mpl. PMID- 7777503 TI - DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans. AB - Intramuscular injection of plasmid DNA expression vectors encoding the three envelope proteins of the hepatitis B virus (HBV) induced humoral responses in C57BL/6 mice specific to several antigenic determinants of the viral envelope. The first antibodies appeared within 1-2 weeks after injection of DNA and included antibodies of the IgM isotype. Over the next few weeks, an IgM to IgG class switch occurred, indicating helper T-lymphocyte activity. Peak IgG titers were reached by 4-8 weeks after a single DNA injection and were maintained for at least 6 months without further DNA injections. The antibodies to the envelope proteins reacted with group- and subtype-specific antigenic determinants of the HBV surface antigen (HBsAg). Expression vectors encoding the major (S) and middle (preS2 plus S) envelope proteins induced antibodies specific to the S protein and preS2 domain, and preS2 antibodies were prominent at early time points. In general, the expression vectors induced humoral responses in mice that mimic those observed in humans during the course of natural HBV infection. PMID- 7777504 TI - A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone sensitive pools of inositolphospholipids. AB - The synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], the immediate precursor of intracellular signals generated by calcium-mobilizing hormones and growth factors, is initiated by the conversion of phosphatidylinositol to phosphatidylinositol 4-phosphate [PtdIns(4)P] by phosphatidylinositol 4-kinase (PtdIns 4-kinase). Although cells contain several PtdIns 4-kinases, the enzyme responsible for regulating the synthesis of hormone sensitive PtdIns(4,5)P2 pools has not been identified. In this report we describe the inhibitory effect of micromolar concentrations of wortmannin (WT) on the synthesis of hormone-sensitive PtdIns(4)P and PtdIns(4,5)P2 pools in intact adrenal glomerulosa cells, and the presence of a WT-sensitive PtdIns 4-kinase in adrenocortical extracts. In addition to its sensitivity to the PtdIns 3-kinase inhibitor WT, this enzyme is distinguished from the recognized membrane-bound PtdIns 4-kinases by its molecular size and weak membrane association. Inhibition of this PtdIns 4-kinase by WT results in rapid loss of the hormone-sensitive PtdIns(4,5)P2 pool in angiotensin II-stimulated glomerulosa cells. Consequently, WT treatment inhibits the sustained but not the initial increases in inositol 1,4,5-trisphosphate and cytoplasmic [Ca2+] in a variety of agonist-stimulated cells, including adrenal glomerulosa cells, NIH 3T3 fibroblasts, and Jurkat lymphoblasts. These results indicate that a specific WT-sensitive PtdIns 4-kinase is critical for the maintenance of the agonist-sensitive polyphosphoinositide pool in several cell types. PMID- 7777505 TI - Dynamics of active lamellae in cultured epithelial cells: effects of expression of exogenous N-ras oncogene. AB - We examined the functional consequences of cellular transformation of rat IAR-2 epithelial cells, by a mutant N-ras oncogene, on the dynamics of active lamellae, structures that play an important role in cell motility, adhesion, and surface receptor capping. Lamellar activity was assessed by measuring the rate of outer edge pseudopodial activity and by analyzing the motility of Con A-coated beads placed on lamellar surfaces with optical tweezers. Although transformation dramatically affected the shape and size of active cellular lamellae, there was little detectable effect on either pseudopodial activity or bead movement. To investigate the potential relationship between functional lamellar activity and the microtubule cytoskeleton, lamellar activity was examined in nontransformed and transformed cells treated with the microtubule-disrupting drug nocodazole. In the absence of microtubules, transformed cells were less polarized and possessed decreased rates of pseudopodial and bead motility. On the basis of these observations, it is suggested that ras-induced transformation of epithelial cells consists of two cytoskeletal modifications: overall diminished actin cytoskeletal dynamics in lamellae and reorganization of the microtubule cytoskeleton that directs pseudopodial activity to smaller polarized lamellae. PMID- 7777506 TI - The folding of GroEL-bound barnase as a model for chaperonin-mediated protein folding. AB - We have analyzed the pathway of folding of barnase bound to GroEL to resolve the controversy of whether proteins can fold while bound to chaperonins (GroEL or Cpn60) or fold only after their release into solution. Four phases in the folding were detected by rapid-reaction kinetic measurements of the intrinsic fluorescence of both wild type and barnase mutants. The phases were assigned from their rate laws, sensitivity to mutations, and correspondence to regain of catalytic activity. At high ratios of denatured barnase to GroEL, 4 mol of barnase rapidly bind per 14-mer of GroEL. At high ratios of GroEL to barnase, 1 mol of barnase binds with a rate constant of 3.5 x 10(7) s-1.M-1. This molecule then refolds with a low rate constant that changes on mutation in parallel with the rate constant for the folding in solution. This rate constant corresponds to the regain of the overall catalytic activity of barnase and increases 15-fold on the addition of ATP to a physiologically relevant value of approximately 0.4 s-1. The multiply bound molecules of barnase that are present at high ratios of GroEL to barnase fold with a rate constant that is also sensitive to mutation but is 10 times higher. If the 110-residue barnase can fold when bound to GroEL and many moles can bind simultaneously, then smaller parts of large proteins should be able to fold while bound. PMID- 7777507 TI - Restriction fragment length polymorphism-coupled domain-directed differential display: a highly efficient technique for expression analysis of multigene families. AB - In this paper, a reverse-transcriptase PCR-based protocol suitable for efficient expression analysis of multigene families is presented. The method combines restriction fragment length polymorphism (RFLP) technology with a gene family specific version of mRNA differential display and hence is called "RFLP-coupled domain-directed differential display. "With this method, expression of all members of a multigene family at many different developmental stages, in diverse tissues and even in different organisms, can be displayed on one gel. Moreover, bands of interest, representing gene family members, are directly accessible to sequence analysis, without the need for subcloning. The method thus enables a detailed, high-resolution expression analysis of known gene family members as well as the identification and characterization of new ones. Here the technique was used to analyze differential expression of MADS-box genes in male and female inflorescences of maize (Zea mays ssp. mays). Six different MADS-box genes could be identified, being either specifically expressed in the female sex or preferentially expressed in male or female inflorescences, respectively. Other possible applications of the method are discussed. PMID- 7777508 TI - Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. AB - The Pax5 transcription factor BSAP (B-cell-specific activator protein) is known to bind to and repress the activity of the immunoglobulin heavy chain 3' alpha enhancer. We have detected an element--designated alpha P--that lies approximately 50 bp downstream of the BSAP binding site 1 and is required for maximal enhancer activity. In vitro binding experiments suggest that the 40-kDa protein that binds to this element (NF-alpha P) is a member of the Ets family present in both B-cell and plasma-cell nuclei. However, in vivo footprint analysis suggests that the alpha P site is occupied only in plasma cells, whereas the BSAP site is occupied in B cells but not in plasma cells. When Pax5 binding to the enhancer in B cells was blocked in vivo by transfection with a triple helix-forming oligonucleotide an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased. The triple-helix-forming oligonucleotide also increased enhancer activity of a transfected construct in B cells, but only when the alpha P site was intact. Pax5 thus regulates the 3' alpha enhancer and immunoglobulin gene transcription by blocking activation by NF alpha P. PMID- 7777509 TI - Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein. AB - The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that beta APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments. PMID- 7777510 TI - Purification and identification of pituitary cytotropic factor. AB - It has been shown that the pituitary contains a cytotropic factor (CTF) that stimulates the secretion of catecholamines by dopaminergic neurons of the hypothalamus. In the present study, CTF was purified from rat pituitaries and found by means of mass spectrometric analysis to be adenosine. This finding was corroborated by the observations that CTF behaves identically to adenosine when subjected to liquid chromatography, is inactivated and converted to inosine by adenosine deaminase, and is qualitatively and quantitatively indistinguishable from adenosine in its biological activity. It is concluded that pituitary adenosine is a trophic factor for hypothalamic dopaminergic neurons. PMID- 7777511 TI - DNA polymerase beta bypasses in vitro a single d(GpG)-cisplatin adduct placed on codon 13 of the HRAS gene. AB - We have examined the capacity of calf thymus DNA polymerases alpha, beta, delta, and epsilon to perform in vitro translesion synthesis on a substrate containing a single d(GpG)-cisplatin adduct placed on codon 13 of the human HRAS gene. We found that DNA synthesis catalyzed by DNA polymerases alpha, delta, and epsilon was blocked at the base preceding the lesion. Addition of proliferating cell nuclear antigen to DNA polymerase delta and replication protein A to DNA polymerase alpha did not restore their capacity to elongate past the adduct. On the other hand, DNA polymerase beta efficiently bypassed the cisplatin adduct. Furthermore, we observed that DNA polymerase beta was the only polymerase capable of primer extension of a 3'-OH located opposite the base preceding the lesion. Likewise, DNA polymerase beta was able to elongate the arrested replication products of the other three DNA polymerases, thus showing its capacity to successfully compete with polymerases alpha, delta, and epsilon in the stalled replication complex. Our data suggest (i) a possible mechanism enabling DNA polymerase beta to bypass a d(GpG)-cisplatin adduct in vitro and (ii) a role for this enzyme in processing DNA damage in vivo. PMID- 7777512 TI - Phosphorylation of the human leukemia inhibitory factor (LIF) receptor by mitogen activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation. AB - We used a bacterially expressed fusion protein containing the entire cytoplasmic domain of the human leukemia inhibitory factor (LIF) receptor to study its phosphorylation in response to LIF stimulation. The dose- and time-dependent relationships for phosphorylation of this construct in extracts of LIF-stimulated 3T3-L1 cells were superimposable with those for the stimulation of mitogen activated protein kinase (MAPK). Indeed, phosphorylation of the cytoplasmic domain of the low-affinity LIF receptor alpha-subunit (LIFR) in Mono Q fractionated, LIF-stimulated 3T3-L1 extracts occurred only in those fractions containing activated MAPK; Ser-1044 served as the major phosphorylation site in the human LIFR for MAPK both in agonist-stimulated 3T3-L1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro. Expression in rat H 35 hepatoma cells of LIFR or chimeric granulocyte-colony-stimulating factor receptor (G-CSFR)-LIFR mutants lacking Ser-1044 failed to affect cytokine stimulated expression of a reporter gene under the control of the beta-fibrinogen gene promoter but eliminated the insulin-induced attenuation of cytokine stimulated gene expression. Thus, our results identify the human LIFR as a substrate for MAPK and suggest a mechanism of heterologous receptor regulation of LIFR signaling occurring at Ser-1044. PMID- 7777513 TI - Full-length myotonin protein kinase (72 kDa) displays serine kinase activity. AB - We describe the full-length (72 kDa) myotonin protein kinase (Mt-PK) and demonstrate its kinase activity. The 72-kDa protein corresponds to the translation product from the first in-frame AUG codon. This protein was found in the cytoplasmic fraction, whereas the previously reported 55-kDa protein was observed in nuclear extracts. Only the 72-kDa protein was phosphorylated by [32P]phosphate in normal human fibroblasts. To investigate the putative kinase activity of Mt-PK, a construct containing the full-length open reading frame of Mt-PK was expressed in bacterial cells. The recombinant Mt-PK autophosphorylates a Ser residue and phosphorylates the synthetic peptide Gly-Arg-Gly-Leu-Ser-Leu Ser-Arg, which contains a Ser residue in the phosphorylation site. We examined phosphorylation of the voltage-dependent Ca(2+)-release channel, or dihydropyridine receptor (DHPR), by recombinant Mt-PK. We observed that the beta subunit of DHPR was phosphorylated in vitro by Mt-PK. A beta-subunit DHPR peptide containing some of the Ser residues predicted to be phosphorylated was synthesized and found to be a substrate for Mt-PK in vitro. We conclude that the 72-kDa Mt-PK has a protein kinase activity specific for Ser residues. PMID- 7777514 TI - Position-dependent variegation of globin transgene expression in mice. AB - Expression of genes in eukaryotes has commonly been analyzed in a whole tissue, and levels of expression have been interpreted as the result of equivalent rates of transcription in every cell. We have produced transgenic mouse lines that express beta-galactosidase under the control of globin promoters linked to the major tissue-specific regulatory element of the alpha-globin locus, which permits the analysis of transgene expression in individual red blood cells. We find that expression of the transgene within all mouse lines is heterocellular. Individual cells either do not express the transgene at all or express it at a level characteristic of that line. The number of beta-galactosidase-expressing cells varies greatly between different lines of transgenic mice at any defined stage of development, but within a transgenic line, individual mice have strikingly similar numbers of expressing cells. This suggests that the degree of heterocellular expression is determined by the site of integration, as is seen in position-effect variegation. PMID- 7777515 TI - Chimeric tumor necrosis factor receptors with constitutive signaling activity. AB - Many hormone and cytokine receptors are crosslinked by their specific ligands, and multimerization is an essential step leading to the generation of a signal. In the case of the tumor necrosis factor (TNF) receptors (TNF-Rs), antibody induced crosslinking is sufficient to trigger a cytolytic effect. However, the quaternary structural requirements for signaling--i.e., the formation of dimers, trimers, or higher-order multimers--have remained obscure. Moreover, it has not been clear whether the 55-kDa or 75-kDa TNF-R is responsible for initiation of cytolysis. We reasoned that an obligate receptor dimer, targeted to the plasma membrane, might continuously signal the presence of TNF despite the actual absence of the ligand. Such a molecule, inserted into an appropriate vector, could be used to project receptor-specific "TNF-like" activity to specific cells and tissues in vivo. Accordingly, we constructed sequences encoding chimeric receptors in which the extracellular domain of the mouse erythropoietin receptor (Epo-R) was fused to the "stem," transmembrane domain, and cytoplasmic domain of the two mouse TNF-Rs. Thus, the Epo-R group was used to drive dimerization of the TNF-R cytoplasmic domain. These chimeric proteins were well expressed in a variety of cell lines and bound erythropoietin at the cell surface. Both the 55 kDa and the 75-kDa Epo/TNF-R chimeras exerted a constitutive cytotoxic effect detected by cotransfection or clonogenic assay. Thus, despite the lack of structural homology between the cytoplasmic domains of the two TNF-Rs, a similar signaling endpoint was observed. Moreover, dimerization (rather than trimerization or higher-order multimerization) was sufficient for elicitation of a biological response. PMID- 7777516 TI - Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A. AB - Analogs of the immunosuppressive cyclic undecapeptide cyclosporin A (CsA) with substitutions in positions 1, 4, 6, and/or 11 were rationally designed to possess substantially diminished or no immunosuppressive activity. When these compounds were assayed for their capacity to interfere with the replication of human immunodeficiency virus, some displayed a potent antiviral activity in newly infected cells. However, only CsA could interfere with virus replication in persistently infected cells. One CsA analog with antiviral activity costimulated the phytohemagglutinin-induced production of interleukin 2 by human lymphocytes. Human immunodeficiency virus particles from drug-exposed cells showed lower infectivity than virions from untreated cells. Thus, these nonimmunosuppressive analogs of CsA constitute a promising class of lead compounds to develop drugs for effective treatment of the acquired immunodeficiency syndrome. PMID- 7777517 TI - Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions. AB - Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression. PMID- 7777518 TI - Two Drosophila nervous system antigens, Nervana 1 and 2, are homologous to the beta subunit of Na+,K(+)-ATPase. AB - A nervous system-specific glycoprotein antigen from adult Drosophila heads, designated Nervana (Nrv), has been purified on the basis of reactivity of its carbohydrate epitope(s) with anti-horseradish peroxidase (HRP) antibodies that are specific markers for Drosophila neurons. Anti-Nrv monoclonal antibodies (mAbs), specific for the protein moiety of Nrv, were used to screen a Drosophila embryo cDNA expression library. Three cDNA clones (designated Nrv1, Nrv2.1, and Nrv2.2) were isolated that code for proteins recognized by anti-Nrv mAbs on Western blots. DNA sequencing and Southern blot analyses established that the cDNA clones are derived from two different genes. In situ hybridization to Drosophila polytene chromosomes showed that the cDNA clones map to the third chromosome near 92C-D. Nrv1 and Nrv2.1/2.2 have open reading frames of 309 and 322/323 amino acids, respectively, and they are 43.4% identical at the amino acid level. The proteins deduced from these clones exhibit significant homology in both primary sequence and predicted topology to the beta subunit of Na+,K(+) ATPase. Immunoaffinity-purified Nrv is associated with a protein (M(r) 100,000) recognized on Western blots by anti-ATPase alpha-subunit mAb. Our results suggest that the Drosophila nervous system-specific antigens Nrv1 and -2 are neuronal forms of the beta subunit of Na+,K(+)-ATPase. PMID- 7777520 TI - Complex flexibility of the transforming growth factor beta superfamily. AB - The transforming growth factors beta (TGF-beta s) are important modulators of growth and differentiation. They are intermolecular disulfide-bonded homodimeric molecules. The monomer fold has a conserved cystine knot and lacks a hydrophobic core. The biological specificity of a given member of the family is believed to be determined by the conformational flexibility of the variable loop regions of the monomer. The monomer subunit assembly in the dimer is stabilized mainly by hydrophobic contacts and a few hydrogen bonds. Since these interactions are nondirectional, we examined subunit assemblies of TGF-beta by using conformational analysis. The different subunit assemblies in TGF-beta 2 dimer were characterized in terms of the intersubunit disulfide torsion. Our analyses show that the subunit assemblies fall into two states: the crystallographically observed gauche+conformation and the previously not reported gauche- conformation, both having almost identical interaction energies. Furthermore, there is significant flexibility in the subunit assembly within the gauche+ and the gauche- states of the disulfide bond. The monomer subunit assembly is independent of the variations about the loop regions. The variations in the loop regions, coupled with flexibility in the monomer assembly, lead to a complex flexibility in the dimer of the TGF-beta superfamily. For the TGF-beta superfamily, the cystine knot acts as a scaffold and complex flexibility provides for biological selectivity. Complex flexibility might provide an explanation for the diverse range of biological activities that these important molecules display. PMID- 7777519 TI - Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain. AB - Signaling by interferon gamma (IFN-gamma) requires two structurally related cell surface proteins: a ligand-binding polypeptide, known as the IFN-gamma receptor (IFN-gamma R), and an accessory factor. However, it is not known whether IFN gamma forms a ternary complex with the IFN-gamma R and accessory factor to initiate signaling. Here we demonstrate complex formation between IFN-gamma and the two proteins, both in solution and at the cell surface. We observe complexes containing ligand, two molecules of IFN-gamma R (designated the IFN-gamma R alpha chain), and one or two molecules of accessory factor (designated the IFN-gamma R beta chain). Transfected cells expressing both IFN-gamma R chains bind IFN-gamma with higher affinity than do cells expressing alpha chain alone. Anti-beta-chain antibodies prevent the beta chain from participating in the ligand-receptor complex, reduce the affinity for IFN-gamma, and block signaling. Soluble alpha- or beta-chain extracellular domains also inhibit function. These results demonstrate that IFN-gamma signals via a high-affinity multisubunit complex that contains two types of receptor chain and suggest a potential approach to inhibiting specific actions of IFN-gamma by blocking the association of receptor subunits. PMID- 7777521 TI - Nascent polypeptide-associated complex protein prevents mistargeting of nascent chains to the endoplasmic reticulum. AB - We show that, after removal of the nascent polypeptide-associated complex (NAC) from ribosome-associated nascent chains, ribosomes synthesizing proteins lacking signal peptides are efficiently targeted to the endoplasmic reticulum (ER) membrane. After this mistargeting, translocation across the ER membrane occurs, albeit less efficiently than for a nascent secretory polypeptide, perhaps because the signal peptide is needed to catalyze the opening of the translocation pore. The mistargeting was prevented by the addition of purified NAC and was shown not to be mediated by the signal recognition particle and its receptor. Instead, it appears to be a consequence of the intrinsic affinity of ribosomes for membrane binding sites, since it can be blocked by competing ribosomes that lack associated nascent polypeptides. We propose that, when bound to a signalless ribosome-associated nascent polypeptide, NAC sterically blocks the site in the ribosome for membrane binding. PMID- 7777522 TI - Identification of functionally important helical faces in transmembrane segments by scanning mutagenesis. AB - We applied mutational analysis to a protein domain that functions in neither catalysis nor binding but, rather, in transmembrane signaling. The domain is part of chemoreceptor Trg from Escherichia coli. It contains four transmembrane segments, two from each subunit of the homodimer. We used cysteine scanning to investigate the functional importance of each of 54 residues in the two transmembrane segments. Cysteines at some positions resulted in subtle but significant reductions in tactic response. Those positions defined a specific helical face on each segment, implying that the segments function as helices. The functionally important faces corresponded to structural, helical packing faces identified independently by biochemical studies. All functionally impaired receptors exhibited altered signaling properties, either reduced signaling upon stimulation or induced signaling in the absence of stimulation. The distribution of substitutions creating these two phenotypes implied that conformational signaling involves movement between the two transmembrane helices within a subunit and that signaling is optimal when stable interactions are maintained across the interface between subunits. PMID- 7777523 TI - Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins. AB - Secretion of anionic endo- and xenobiotics is essential for the survival of animal and plant cells; however, the underlying molecular mechanisms remain uncertain. To better understand one such model system--i.e., secretion of bile acids by the liver--we utilized a strategy analogous to that employed to identify the multidrug resistance (mdr) genes. We synthesized the methyl ester of glycocholic acid (GCE), which readily enters cells, where it is hydrolyzed to yield glycocholic acid, a naturally occurring bile acid. The rat hepatoma-derived HTC cell line gradually acquired resistance to GCE concentrations 20-fold higher than those which inhibited growth of naive cells, yet intracellular accumulation of radiolabel in resistant cells exposed to [14C]GCE averaged approximately 25% of that in nonresistant cells. As compared with nonresistant cells, resistant cells also exhibited (i) cross-resistance to colchicine, a known mdr substrate, but not to other noxious substances transported by hepatocytes; (ii) increased abundance on Northern blot of mRNA species up to 7-10 kb recognized by a probe for highly conserved nucleotide-binding domain (NBD) sequences of ATP-binding cassette (ABC) proteins; (iii) increased abundance, as measured by RNase protection assay, of mRNA fragments homologous to a NBD cRNA probe; and (iv) dramatic overexpression, as measured by Western blotting and immunofluorescence, of a group of 150- to 200-kDa plasma membrane proteins recognized by a monoclonal antibody against a region flanking the highly conserved NBD of mdr/P glycoproteins. Finally, Xenopus laevis oocytes injected with mRNA from resistant cells and incubated with [14C]GCE secreted radiolabel more rapidly than did control oocytes. Enhanced secretion of glycocholic acid in this cell line is associated with overexpression of ABC/mdr-related proteins, some of which are apparently novel and are likely to include a bile acid transport protein. PMID- 7777524 TI - Library of libraries: approach to synthetic combinatorial library design and screening of "pharmacophore" motifs. AB - Construction of synthetic combinatorial libraries is described that allows for the generation of a library of motifs rather than a library of compounds. Peptide libraries based on this strategy were synthesized and screened with model targets streptavidin and anti-beta-endorphin antibody. The screens resulted in observation of expected motifs providing evidence of the effectiveness of the suggested approach. PMID- 7777525 TI - Translational termination efficiency in mammals is influenced by the base following the stop codon. AB - The base following stop codons in mammalian genes is strongly biased, suggesting that it might be important for the termination event. This proposal has been tested experimentally both in vivo by using the human type I iodothyronine deiodinase mRNA and the recoding event at the internal UGA codon and in vitro by measuring the ability of each of the 12 possible 4-base stop signals to direct the eukaryotic polypeptide release factor to release a model peptide, formylmethionine, from the ribosome. The internal UGA in the deiodinase mRNA is used as a codon for incorporation of selenocysteine into the protein. Changing the base following this UGA codon affected the ratio of termination to selenocysteine incorporation in vivo at this codon: 1:3 (C or U) and 3:1 (A or G). These UGAN sequences have the same order of efficiency of termination as was found with the in vitro termination assay (4th base: A approximately G >> C approximately U). The efficiency of in vitro termination varied in the same manner over a 70-fold range for the UAAN series and over an 8-fold range for the UGAN and UAGN series. There is a correlation between the strength of the signals and how frequently they occur at natural termination sites. Together these data suggest that the base following the stop codon influences translational termination efficiency as part of a larger termination signal in the expression of mammalian genes. PMID- 7777526 TI - Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis. AB - The retinoblastoma susceptibility gene (Rb) participates in controlling the G1/S phase transition, presumably by binding and inactivating E2F transcription activator family members. Mouse embryonic fibroblasts (MEFs) with no, one, or two inactivated Rb genes were used to determine the specific contributions of Rb protein to cell cycle progression and gene expression. MEFs lacking both Rb alleles (Rb-/-) entered S phase in the presence of the dihydrofolate reductase inhibitor methotrexate. Two E2F target genes, dihydrofolate reductase and thymidylate synthase, displayed elevated mRNA and protein levels in Rb- MEFs. Since absence of functional Rb protein in MEFs is sufficient for S-phase entry under growth-limiting conditions, these data indicate that the E2F complexes containing Rb protein, and not the Rb-related proteins p107 and p130, may be rate limiting for the G1/S transition. Antineoplastic drugs caused accumulation of p53 in the nuclei of both Rb+/+ and Rb-/- MEFs. While p53 induction led to apoptosis in Rb-/- MEFs, Rb+/- and Rb+/+ MEFs underwent cell cycle arrest without apoptosis. These results reveal that diverse growth signals work through Rb to regulate entry into S phase, and they indicate that absence of Rb protein produces a constitutive DNA replication signal capable of activating a p53 associated apoptotic response. PMID- 7777527 TI - Drosophila 5-HT2 serotonin receptor: coexpression with fushi-tarazu during segmentation. AB - Serotonin, first described as a neurotransmitter in invertebrates, has been investigated mostly for its functions in the mature central nervous system of higher vertebrates. Serotonin receptor diversity has been described in the mammalian brain and in insects. We report the isolation of a cDNA coding for a Drosophila melanogaster serotonin receptor that displays a sequence, a gene organization, and pharmacological properties typical of the mammalian 5-HT2 serotonin receptor subtype. Its mRNA can be detected in the adult fly; moreover, a high level of expression occurs at 3 hr of Drosophila embryogenesis. This early embryonic expression is surprisingly organized in a seven-stripe pattern that appears at the cellular blastoderm stage. In addition, this pattern is in phase with that of the even-parasegment-expressed pair-rule gene fushi-tarazu and is similarly modified by mutations affecting segmentation genes. Simultaneously with this pair-rule expression, the complete machinery of serotonin synthesis is present and leads to a peak of ligand concomitant with a peak of 5-HT2-specific receptor sites in blastoderm embryos. PMID- 7777528 TI - Structure and stability of a second molten globule intermediate in the apomyoglobin folding pathway. AB - Apomyoglobin folding proceeds through a molten globule intermediate (low-salt form; I1) that has been characterized by equilibrium (pH 4) and kinetic (pH 6) folding experiments. Of the eight alpha-helices in myoglobin, three (A, G, and H) are structured in I1, while the rest appear to be unfolded. Here we report on the structure and stability of a second intermediate, the trichloroacetate form of the molten globule intermediate (I2), which is induced either from the acid unfolded protein or from I1 by > or = 5 mM sodium trichloroacetate. Circular dichroism measurements monitoring urea- and acid-induced unfolding indicate that I2 is more highly structured and more stable than I1. Although I2 exhibits properties closer to those of the native protein, one-dimensional NMR spectra show that it maintains the lack of fixed side-chain structure that is the hallmark of a molten globule. Amide proton exchange and 1H-15N two-dimensional NMR experiments are used to identify the source of the extra helicity observed in I2. The results reveal that the existing A, G, and H helices present in I1 have become more stable in I2 and that a fourth helix--the B helix--has been incorporated into the molten globule. Available evidence is consistent with I2 being an on-pathway intermediate. The data support the view that apomyoglobin folds in a sequential fashion through a single pathway populated by intermediates of increasing structure and stability. PMID- 7777529 TI - Involvement of the cell-cycle inhibitor Cip1/WAF1 and the E1A-associated p300 protein in terminal differentiation. AB - The mechanism of cell cycle withdrawal during terminal differentiation is poorly understood. We report here that the cyclin-dependent kinase (CDK) inhibitor p21Cip1/WAF1 is induced at early times of both keratinocyte and myoblast differentiation. p21Cip1/WAF1 induction is accompanied by a drastic inhibition of total Cdk2, as well as p21Cip1/WAF1-associated CDK kinase activities. p21Cip1/WAF1 has been implicated in p53-mediated G1 arrest and apoptosis. In keratinocyte differentiation, Cip1/WAF1 induction is observed even in cells derived from p53-null mice. Similarly, keratinocyte differentiation is associated with induction of Cip1/WAF1 promoter activity in both wild-type and p53-negative keratinocytes. Induction of the Cip1/WAF1 promoter upon differentiation is abolished by expression of an adenovirus E1A oncoprotein (d1922/947), which is unable to bind p105-Rb, p107, or cyclin A but which still binds the nuclear phosphoprotein p300. Overexpression of p300 can suppress the E1A effect, independent of its direct binding to E1A. Thus, terminal differentiation-induced growth arrest in both keratinocyte and myoblast systems is associated with induction of Cip1/WAF1 expression. During keratinocyte differentiation, Cip1/WAF1 induction does not require p53 but depends on the transcriptional modulator p300. PMID- 7777530 TI - Binding of purified multiple antibiotic-resistance repressor protein (MarR) to mar operator sequences. AB - Elevated expression of the marORAB multiple antibiotic-resistance operon enhances the resistance of Escherichia coli to various medically significant antibiotics. Transcription of the operon is repressed in vivo by the marR-encoded protein, MarR, and derepressed by salicylate and certain antibiotics. The possibility that repression results from MarR interacting with the marO operator-promoter region was studied in vitro using purified MarR and a DNA fragment containing marO. MarR formed at least two complexes with marO DNA, bound > 30-fold more tightly to it than to salmon sperm DNA, and protected two separate 21-bp sites within marO from digestion by DNase I. Site I abuts the downstream side of the putative -35 transcription-start signal and includes 4 bp of the -10 signal. Site II begins 13 bp downstream of site I, ending immediately before the first base pair of marR. Site II, approximately 80% homologous to site I, is not required for repression since a site II-deleted mutant (marO133) was repressed in trans by wild-type MarR. The absence of site II did not prevent MarR from complexing with the site I of marO133. Salicylate bound to MarR (Kd approximately 0.5 mM) and weakened the interaction of MarR with sites I and II. Thus, repression of the mar operon, which curbs the antibiotic resistance of E. coli, correlates with the formation of MarR-site I complexes. Salicylate appears to induce the mar operon by binding to MarR and inhibiting complex formation, whereas tetracycline and chloramphenicol, which neither bind MarR nor inhibit complex formation, must induce by an indirect mechanism. PMID- 7777532 TI - Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. AB - Myotonic dystrophy is caused by an expansion of a CTG triplet repeat sequence in the 3' noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. This report demonstrates that a DNase I hypersensitive site is positioned 3' of the triplet repeat in the wild-type allele in both fibroblasts and skeletal muscle cells. In three unrelated individuals with myotonic dystrophy that have large expansions of the triplet repeat, the allele with the triplet repeat expansion exhibited both overall DNase I resistance and inaccessibility of nucleases to the adjacent hypersensitive site. These results indicate that the triplet repeat expansion alters the adjacent chromatin structure, establishing a region of condensed chromatin, and suggests a molecular mechanism for myotonic dystrophy. PMID- 7777531 TI - Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1. AB - Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies. PMID- 7777533 TI - The dietary adaptations of European Miocene catarrhines. AB - European Miocene "apes" have been known for nearly a century and a half but their phylogenetic significance is only now becoming apparent with the recent discovery of many relatively complete remains. Some appear to be close in time and morphology to the last common ancestor of modern great apes and humans. The current study is an attempt to reconstruct the diets of these fossils on the basis of quantitative data. Results suggest that these primates varied more greatly in their diets than modern apes, with adaptations ranging from hard object feeding to soft-object frugivory to folivory. PMID- 7777535 TI - Adaptive reversion of an episomal frameshift mutation in Escherichia coli requires conjugal functions but not actual conjugation. AB - Adaptive reversion of a lac- frameshift mutation in Escherichia coli appears to be due to DNA polymerase errors, implying that DNA is being synthesized although the cells are not dividing. Here we report that the production of adaptive lac+ revertants (i) is much higher when the mutational target is on the F' episome than when it is on the bacterial chromosome; (ii) is enhanced by functions required for conjugation; but (iii) does not require conjugation per se. These results suggest that, in static cells, DNA synthesis is initiated from the conjugal origin of transfer. Mutations may arise as polymerase errors during this synthesis or during synthesis stimulated by recombination among the multiple gene copies. PMID- 7777534 TI - Activation of Stat5 by interleukin 2 requires a carboxyl-terminal region of the interleukin 2 receptor beta chain but is not essential for the proliferative signal transmission. AB - The high-affinity interleukin 2 (IL-2) receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta c, and IL-2R gamma c chains. Two members of the Janus kinase family, Jak1 and Jak3, are associated with IL-2R beta c and IL 2R gamma c, respectively, and they are activated upon IL-2 stimulation. The cytokine-mediated Jak kinase activation usually results in the activation of a family of latent transcription factors termed Stat (signal transducer and activator of transcription) proteins. Recently, the IL-2-induced Stat protein was purified from human lymphocytes and found to be the homologue of sheep Stat5/mammary gland factor. We demonstrate that the human Stat5 is activated by IL-2 and that Jak3 is required for the efficient activation. The cytoplasmic region of the IL-2R beta c chain required for activation of Stat5 is mapped within the carboxyl-terminal 147 amino acids. On the other hand, this region is not essential for IL-2-induced cell proliferation. PMID- 7777536 TI - Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division. AB - Growth factors have been defined by their ability to promote the proliferative expansion of receptor-bearing cells. For example, antigen-activated T cells expressing the alpha beta gamma form of the interleukin 2 (IL-2) receptor will proliferate in response to IL-2. In contrast, resting T cells, which express the IL-2 receptor beta and gamma chains, do not proliferate in response to IL-2. We demonstrate that the survival of resting T cells following gamma irradiation is greatly enhanced by pretreatment with IL-2. The radioprotective effect of IL-2 is dose dependent, does not result from the induction of cell proliferation, and does not require expression of the IL-2 receptor alpha chain. Thus, the beta gamma IL-2 receptor expressed on resting T cells can transduce signals that promote cell survival without committing the T cell to undergo cell division. IL 4 and IL-7, but not IL-1, IL-3, or IL-6, were also found to enhance the survival of quiescent T cells following gamma irradiation. Thus, certain growth factor receptor interactions can serve to maintain cell viability in a manner that is independent of their ability to initiate or maintain cell proliferation. These data may have important implications for the use of growth factors in patients being treated with radiation and/or chemotherapy. PMID- 7777537 TI - The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver. AB - Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues. PMID- 7777538 TI - Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sezary patients. AB - Sezary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease. PMID- 7777539 TI - A simple test of the vicarious trial-and-error hypothesis of hippocampal function. AB - Vicarious trial-and-error (VTE) is a term that Muenzinger and Tolman used to describe the rat's conflict-like behavior before responding to choice. Recently, VTE was proposed as a mechanism alternative to the concept of "cognitive map" in accounts of hippocampal function. That is, many phenomena of impaired learning and memory related to hippocampal interventions may be explained by behavioral first principles: reduced conflicting, incipient, pre-choice tendencies to approach and avoid. The nonspatial black-white discrimination learning and VTE behavior of the rat were investigated. Hippocampal-lesioned and sham-lesioned animals were trained for 25 days (20 trials per day) starting at 60 days of age. Each movement of the head from one discriminative stimulus to the other was counted as a VTE instance. Lesioned rats had fewer VTEs than sham controls, and the former learned much more slowly or never learned. After learning, VTE frequency declined. Male and female rats showed no significant differences in VTE behavior or discrimination learning. PMID- 7777540 TI - Chromosomal insertion of foreign (adenovirus type 12, plasmid, or bacteriophage lambda) DNA is associated with enhanced methylation of cellular DNA segments. AB - Insertion of foreign DNA into an established mammalian genome can extensively alter the patterns of cellular DNA methylation. Adenovirus type 12 (Ad12) transformed hamster cells, Ad12-induced hamster tumor cells, or hamster cells carrying integrated DNA of bacteriophage lambda were used as model systems. DNA methylation levels were examined by cleaving cellular DNA with Hpa II, Msp I, or Hha I, followed by Southern blot hybridization with 32P-labeled, randomly selected cellular DNA probes. For several, but not all, cellular DNA segments investigated, extensive increases in DNA methylation were found in comparison with the methylation patterns in BHK21 or primary Syrian hamster cells. In eight different Ad12-induced hamster tumors, moderate increases in DNA methylation were seen. Increased methylation of cellular genes was also documented in two hamster cell lines with integrated Ad12 DNA without the Ad12-transformed phenotype, in one cloned BHK21 cell line with integrated plasmid DNA, and in at least three cloned BHK21 cell lines with integrated lambda DNA. By fluorescent in situ hybridization, the cellular hybridization probes were located to different hamster chromosomes. The endogenous intracisternal A particle genomes showed a striking distribution on many hamster chromosomes, frequently on their short arms. When BHK21 hamster cells were abortively infected with Ad12, increases in cellular DNA methylation were not seen. Thus, Ad12 early gene products were not directly involved in increasing cellular DNA methylation. We attribute the alterations in cellular DNA methylation, at least in part, to the insertion of foreign DNA. Can alterations in the methylation profiles of hamster cellular DNA contribute to the generation of the oncogenic phenotype? PMID- 7777541 TI - A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3. AB - Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome 1p polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by D1Z2 and proximally by D1S228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of 1p36, and from a neuroblastoma cell line with a small 1p36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of 1p36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes--DAN, ID3 (heir 1), CDC2L1 (p58), and TNFR2--were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within 1p36.2-36.3, eliminating 33 centimorgans of proximal 1p36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with 1p36 LOH. PMID- 7777542 TI - Misexpression of the white (w) gene triggers male-male courtship in Drosophila. AB - We report here that the general ectopic expression of a tryptophan/guanine transmembrane transporter gene, white (w), induces male-male courtship in Drosophila. Activation of a hsp-70/miniwhite (mini-w) transgene in mature males results in a marked change in their sexual behavior such that they begin to vigorously court other mature males. In transformant populations containing equal numbers of both sexes, most males participate, thus forming male-male courtship chains, circles, and lariats. Mutations that ablate the w transgene function also abolish this inducible behavior. Female sexual behavior does not appear to be altered by ectopic w expression. By contrast, when exposed to an active homosexual courtship environment, non-transformant males alter their behavior and actively participate in the male-male chaining. These findings demonstrate that, in Drosophila, both genetic and environmental factors play a role in male sexual behavior. PMID- 7777543 TI - Neural-network-based classification of cognitively normal, demented, Alzheimer disease and vascular dementia from single photon emission with computed tomography image data from brain. AB - Single photon emission with computed tomography (SPECT) hexamethylphenylethyleneamineoxime technetium-99 images were analyzed by an optimal interpolative neural network (OINN) algorithm to determine whether the network could discriminate among clinically diagnosed groups of elderly normal, Alzheimer disease (AD), and vascular dementia (VD) subjects. After initial image preprocessing and registration, image features were obtained that were representative of the mean regional tissue uptake. These features were extracted from a given image by averaging the intensities over various regions defined by suitable masks. After training, the network classified independent trials of patients whose clinical diagnoses conformed to published criteria for probable AD or probable/possible VD. For the SPECT data used in the current tests, the OINN agreement was 80 and 86% for probable AD and probable/possible VD, respectively. These results suggest that artificial neural network methods offer potential in diagnoses from brain images and possibly in other areas of scientific research where complex patterns of data may have scientifically meaningful groupings that are not easily identifiable by the researcher. PMID- 7777544 TI - Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. AB - One of the membrane guanylyl cyclases (GCs), RetGC, is expressed predominantly in photoreceptors. No extracellular ligand has been described for RetGC, but it is sensitive to activation by a soluble 24-kDa protein (p24) and is inhibited by Ca2+. This enzyme is, therefore, thought to play a role in resynthesizing cGMP for photoreceptor recovery or adaptation. By screening a human retinal cDNA library at low stringency with the cytoplasmic domains from four cyclases, we cloned cDNAs encoding a membrane CG that is most closely related to RetGC. We have named this GC RetGC-2, and now term the initially described RetGC RetGC-1. By in situ hybridization, mRNA encoding RetGC-2 is found only in the outer nuclear layer and inner segments of photoreceptor cells. By using synthetic peptide antiserum specific for each RetGC subtype, RetGC-2 can be distinguished from RetGC-1 as a slightly smaller protein in immunoblots of bovine rod outer segments. Membrane GC activity of recombinant RetGC-2 expressed in human embryonic kidney 293 cells is stimulated by the activator p24 and is inhibited by Ca2+ with an EC50 value of 50-100 nM. Our data reveal a previously unappreciated diversity of photoreceptor GCs. PMID- 7777545 TI - Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination. AB - Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2) transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2 secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction. PMID- 7777546 TI - Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. AB - The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors which inhibit cell cycle progression in many cell types. The TGF beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and the activities of the G1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of small proteins, p21 (WAF1, Cip1), p27Kip1, p16, and p15INK4B, that physically associate with cyclins, cyclin-dependent kinases, or cyclin-Cdk complexes. p21 has been previously shown to be transcriptionally induced by DNA damage through p53 as a mediator. We demonstrate that TGF-beta also causes a rapid transcriptional induction of p21, suggesting that p21 can respond to both intracellular and extracellular signals for cell cycle arrest. In contrast to DNA damage, however, induction of p21 by TGF-beta is not dependent on wild-type p53. The cell line studied in these experiments, HaCaT, contains two mutant alleles of p53, which are unable to activate transcription from the p21 promoter when overexpressed. In addition, TGF-beta and p53 act through distinct elements in the p21 promoter. Taken together, these findings suggest that TGF-beta can induce p21 through a p53-independent pathway. Previous findings have implicated p27Kip1 and p15INK2B as effectors mediating the TGF-beta growth inhibitory effect. These results demonstrate that a single extracellular antiproliferative signal, TGF beta, can act through multiple signaling pathways to elicit a growth arrest response. PMID- 7777547 TI - A class of single-stranded telomeric DNA-binding proteins required for Rap1p localization in yeast nuclei. AB - We have identified a class of proteins that bind single-stranded telomeric DNA and are required for the nuclear organization of telomeres and/or telomere associated proteins. Rlf6p was identified by its sequence similarity to Gbp1p, a single-stranded telomeric DNA-binding protein from Chlamydomonas reinhardtii. Rlf6p and Gbp1p bind yeast single-stranded G-strand telomeric DNA. Both proteins include at least two RNA recognition motifs, which are found in many proteins that interact with single-stranded nucleic acids. Disruption of RLF6 alters the distribution of repressor/activator protein 1 (Rap1p), a telomere-associated protein. In wild-type yeast cells, Rap1p localizes to a small number of perinuclear spots, while in rlf6 cells Rap1p appears diffuse and nuclear. Interestingly, telomere position effect and telomere length control, which require RAP1, are unaffected by rlf6 mutations, demonstrating that Rap1p localization can be uncoupled from other Rap1p-dependent telomere functions. In addition, expression of Chlamydomonas GBP1 restores perinuclear, punctate Rap1p localization in rlf6 mutant cells. The functional complementation of a fungal gene by an algal gene suggests that Rlf6p and Gbp1p are members of a conserved class of single-stranded telomeric DNA-binding proteins that influence nuclear organization. Furthermore, it demonstrates that, despite their unusual codon bias, C. reinhardtii genes can be efficiently translated in Saccharomyces cerevisiae cells. PMID- 7777550 TI - Genomic DNA fingerprinting by restriction fragment end labeling. AB - A typing method for bacteria was developed and applied to several species, including Escherichia coli and Actinobacillus actinomycetemcomitans. Total genomic DNA was digested with a restriction endonuclease, and fragments were enabled with [alpha-32P]dATP by using the Klenow fragment of DNA polymerase and separated by electrophoresis in 6% polyacrylamide/8 M urea (sequencing gel). Depending on the restriction endonuclease and the bacterium, the method produced approximately 30-50 well-separated fragments in the size range of 100-400 nucleotides. For A. actinomycetemcomitans, all strains had bands in common. Nevertheless, many polymorphisms could be observed, and the 31 strains tested could be classified into 29 distinct types. Furthermore, serotype-specific fragments could be assigned for the three serotypes investigated. The method described is very sensitive, allowing more distinct types to be distinguished than other commonly used typing methods. When the method was applied to 10 other clinically relevant bacterial species, both species-specific bands and strain specific bands were found. Isolates from different locations of one patient showed indistinguishable patterns. Computer-assisted analysis of the DNA fingerprints allowed the determination of similarity coefficients. It is concluded that genomic fingerprinting by restriction fragment end labeling (RFEL) is a powerful and generally applicable technique to type bacterial species. PMID- 7777549 TI - Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections. AB - A synthetic heptadecapeptide, CKS-17, represents the highly conserved amino acid sequences occurring within the transmembrane envelope protein of many animal and human retroviruses. CKS-17 has been demonstrated to exhibit suppressive properties for numerous immune functions. We have recently shown that CKS-17 acts as an immunomodulatory epitope causing an imbalance of human type 1 and type 2 cytokine production and suppression of cell-mediated immunities. cAMP, an intracellular second messenger, plays an important role in regulation of cytokine biosynthesis--i.e., elevation of intracellular cAMP levels selectively inhibits type 1 cytokine production but has no effect or enhances type 2 cytokine production. Here, we demonstrate that CKS-17 induces dramatic rises in the intracellular cAMP levels of a human monocyte cell line and of human peripheral blood mononuclear cells in a time- and dose-dependent manner. A peptide corresponding to the reverse sequence of CKS-17, used as control, has no effect on intracellular cAMP levels. The cAMP-inducing ability of CKS-17 is significantly blocked by SQ-22536, an inhibitor of adenylate cyclase. These results indicate that CKS-17, a highly conserved component of the transmembrane proteins of immunosuppressive retroviruses, induces increased intracellular levels of cAMP via activation of adenylate cyclase and suggest that this retroviral envelope peptide may differentially modulate type 1 and type 2 cytokine production through elevation of intracellular cAMP levels. PMID- 7777548 TI - Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain V beta subsets. AB - The human immunodeficiency virus 1 (HIV-1) replicates more efficiently in T-cell lines expressing T-cell receptors derived from certain V beta genes, V beta 12 in particular, suggesting the effects of a superantigen. The targeted V beta 12 subset was not deleted in HIV-1-infected patients. It was therefore possible that it might represent an in vivo viral reservoir. Viral load was assessed by quantitative PCR with gag primers and with an infectivity assay to measure competent virus. It was shown that the tiny V beta 12 subset (1-2% of T cells) often has a higher viral load than other V beta subsets in infected patients. Selective HIV-1 replication in V beta 12 cells was also observed 6-8 days after in vitro infection of peripheral blood lymphocytes from normal, HIV-1 negative donors. Viral replication in targeted V beta subsets may serve to promote a biologically relevant viral reservoir. PMID- 7777551 TI - Emergent spindle oscillations and intermittent burst firing in a thalamic model: specific neuronal mechanisms. AB - The rhythmogenesis of 10-Hz sleep spindles is studied in a large-scale thalamic network model with two cell populations: the excitatory thalamocortical (TC) relay neurons and the inhibitory nucleus reticularis thalami (RE) neurons. Spindle-like bursting oscillations emerge naturally from reciprocal interactions between TC and RE neurons. We find that the network oscillations can be synchronized coherently, even though the RE-TC connections are random and sparse, and even though individual neurons fire rebound bursts intermittently in time. When the fast gamma-aminobutyrate type A synaptic inhibition is blocked, synchronous slow oscillations resembling absence seizures are observed. Near maximal network synchrony is established with even modest convergence in the RE to-TC projection (as few as 5-10 RE inputs per TC cell suffice). The hyperpolarization-activated cation current (Ih) is found to provide a cellular basis for the intermittency of rebound bursting that is commonly observed in TC neurons during spindles. Such synchronous oscillations with intermittency can be maintained only with a significant degree of convergence for the TC-to-RE projection. PMID- 7777552 TI - Mechanisms underlying the sensitivity of songbird forebrain neurons to temporal order. AB - Neurons in the songbird forebrain area HVc (hyperstriatum ventrale pars caudale or high vocal center) are sensitive to the temporal structure of the bird's own song and are capable of integrating auditory information over a period of several hundred milliseconds. Extracellular studies have shown that the responses of some HVc neurons depend on the combination and temporal order of syllables from the bird's own song, but little is known about the mechanisms underlying these response properties. To investigate these mechanisms, we recorded intracellular responses to a set of auditory stimuli designed to assess the degree of dependence of the responses on temporal context. This report provides evidence that HVc neurons encode information about temporal structure by using a variety of mechanisms including syllable-specific inhibition, excitatory postsynaptic potentials with a range of different time courses, and burst-firing nonlinearity. The data suggest that the sensitivity of HVc neurons to temporal combinations of syllables results from the interactions of several cells and does not arise in a single step from afferent inputs alone. PMID- 7777553 TI - Cortical correlate of pattern backward masking. AB - The perception of a briefly presented shape is strongly impaired when it is followed by another pattern, a phenomenon called backward masking. We found that the vast majority of a sample of shape-selective neurons in the macaque inferior temporal cortex respond selectively to backward-masked shapes, although these shapes could not be discriminated by human and monkey subjects. However, this selective response was brief, since it was either interrupted by the mask or overridden by a response to the mask itself. We show that reliable discrimination of briefly presented shapes by single neurons depends on the temporal integration of the response. Presentation of the mask, however, reduces the number of spikes available for integration, explaining backward masking. These results also provide direct neurophysiological evidence for the "interruption theory" of backward masking. PMID- 7777555 TI - Significant discrepancies between van't Hoff and calorimetric enthalpies. AB - In this paper we show that the usual assumption in studies of the temperature variation of equilibrium constants for equilibria of the form A+B <-->AB that a plot of ln K vs. 1/T (K = equilibrium constant, T = temperature in degrees kelvin) is a straight line with slope equal to -delta HvH/R (delta HvH = van't Hoff or apparent enthalpy, R = gas constant) is not valid in many cases. In all the cases considered here, delta HvH is temperature dependent and is significantly different from the true or calorimetrically measured enthalpy, and the respective values for delta Cp are also significantly different. PMID- 7777554 TI - Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo. AB - Polyamide ("peptide") nucleic acids (PNAs) are molecules with antigene and antisense effects that may prove to be effective neuropharmaceuticals if these molecules are enabled to undergo transport through the brain capillary endothelial wall, which makes up the blood-brain barrier in vivo. The model PNA used in the present studies is an 18-mer that is antisense to the rev gene of human immunodeficiency virus type 1 and is biotinylated at the amino terminus and iodinated at a tyrosine residue near the carboxyl terminus. The biotinylated PNA was linked to a conjugate of streptavidin (SA) and the OX26 murine monoclonal antibody to the rat transferrin receptor. The blood-brain barrier is endowed with high transferrin receptor concentrations, enabling the OX26-SA conjugate to deliver the biotinylated PNA to the brain. Although the brain uptake of the free PNA was negligible following intravenous administration, the brain uptake of the PNA was increased at least 28-fold when the PNA was bound to the OX26-SA vector. The brain uptake of the PNA bound to the OX26-SA vector was 0.1% of the injected dose per gram of brain at 60 min after an intravenous injection, approximating the brain uptake of intravenously injected morphine. The PNA bound to the OX26-SA vector retained the ability to bind to synthetic rev mRNA as shown by RNase protection assays. In summary, the present studies show that while the transport of PNAs across the blood-brain barrier is negligible, delivery of these potential neuropharmaceutical drugs to the brain may be achieved by coupling them to vector mediated peptide-drug delivery systems. PMID- 7777556 TI - Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes. AB - The nucleotide sequences of four genes encoding Trimeresurus gramineus (green habu snake, crotalinae) venom gland phospholipase A2 (PLA2; phosphatidylcholine 2 acylhydrolase, EC 3.1.1.4) isozymes were compared internally and externally with those of six genes encoding Trimeresurus flavoviridis (habu snake, crotalinae) venom gland PLA2 isozymes. The numbers of nucleotide substitutions per site (KN) for the noncoding regions including introns were one-third to one-eighth of the numbers of nucleotide substitutions per synonymous site (KS) for the protein coding regions of exons, indicating that the noncoding regions are much more conserved than the protein-coding regions. The KN values for the introns were found to be nearly equivalent to those of introns of T. gramineus and T. flavoviridis TATA box-binding protein genes, which are assumed to be a general (nonvenomous) gene. Thus, it is evident that the introns of venom gland PLA2 isozyme genes have evolved at a similar rate to those of nonvenomous genes. The numbers of nucleotide substitutions per nonsynonymous site (KA) were close to or larger than the KS values for the protein-coding regions in venom gland PLA2 isozyme genes. All of the data combined reveal that Darwinian-type accelerated evolution has universally occurred only in the protein-coding regions of crotalinae snake venom PLA2 isozyme genes. PMID- 7777557 TI - Direct detection and isolation of restriction landmark genomic scanning (RLGS) spot DNA markers tightly linked to a specific trait by using the RLGS spot bombing method. AB - We have developed a technique for isolating DNA markers tightly linked to a target region that is based on RLGS, named RLGS spot-bombing (RLGS-SB). RLGS-SB allows us to scan the genome of higher organisms quickly and efficiently to identify loci that are linked to either a target region or gene of interest. The method was initially tested by analyzing a C57BL/6-GusS mouse congenic strain. We identified 33 variant markers out of 10,565 total loci in a 4.2-centimorgan (cM) interval surrounding the Gus locus in 4 days of laboratory work. The validity of RLGS-SB to find DNA markers linked to a target locus was also tested on pooled DNA from segregating backcross progeny by analyzing the spot intensity of already mapped RLGS loci. Finally, we used RLGS-SB to identify DNA markers closely linked to the mouse reeler (rl) locus on chromosome 5 by phenotypic pooling. A total of 31 RLGS loci were identified and mapped to the target region after screening 8856 loci. These 31 loci were mapped within 11.7 cM surrounding rl. The average density of RLGS loci located in the rl region was 0.38 cM. Three loci were closely linked to rl showing a recombination frequency of 0/340, which is < 1 cM from rl. Thus, RLGS-SB provides an efficient and rapid method for the detection and isolation of polymorphic DNA markers linked to a trait or gene of interest. PMID- 7777558 TI - Transient transfection and expression of firefly luciferase in Giardia lamblia. AB - We have developed a gene transfer system for the protozoan parasite Giardia lamblia. This organism is responsible for many cases of diarrhea worldwide and is considered to be one of the most primitive eukaryotes. Expression of a heterologous gene was detected in this parasite after electroporation with appropriate DNA constructs. We constructed a series of transfection plasmids using flanking sequences of the Giardia glutamate dehydrogenase (GDH) gene to drive expression of the firefly luciferase reporter gene. The optimal construct consisted of a GDH/luciferase fusion gene in which the first 18 codons of the GDH gene immediately preceded the luciferase gene; this fusion gene was flanked by the upstream and downstream sequences of the GDH gene. Electroporation of this construct into Giardia yielded luciferase activity that was 3000- to 50,000-fold above background. Removal of either the 5' or 3' GDH flanking sequences from this construct resulted in significantly reduced luciferase activity, and removal of both flanking sequences reduced luciferase activity to background levels. Luciferase activity was proportional to the amount of DNA electroporated and was maximal at 6 hr after electroporation. PMID- 7777559 TI - Evidence for five divergent thioredoxin h sequences in Arabidopsis thaliana. AB - Five different clones encoding thioredoxin homologues were isolated from Arabidopsis thaliana cDNA libraries. On the basis of the sequences they encode divergent proteins, but all belong to the cytoplasmic thioredoxins h previously described in higher plants. The five proteins obtained by overexpressing the coding sequences in Escherichia coli present typical thioredoxin activities (NADP(+)-malate dehydrogenase activation and reduction by Arabidopsis thioredoxin reductase) despite the presence of a variant active site, Trp-Cys-Pro-Pro-Cys, in three proteins in place of the canonical Trp-Cys-Gly-Pro-Cys sequence described for thioredoxins in prokaryotes and eukaryotes. Southern blots show that each cDNA is encoded by a single gene but suggest the presence of additional related sequences in the Arabidopsis genome. This very complex diversity of thioredoxins h is probably common to all higher plants, since the Arabidopsis sequences appear to have diverged very early, at the beginning of plant speciation. This diversity allows the transduction of a redox signal into multiple pathways. PMID- 7777560 TI - Strand specificity in the transcriptional targeting of recombination at immunoglobulin switch sequences. AB - B-lymphocyte-specific class switch recombination is known to occur between pairs of 2- to 10-kb switch regions located immediately upstream of the immunoglobulin constant heavy-chain genes. Others have shown that the recombination is temporally correlated with the induction of transcription at the targeted switch regions. To determine whether this temporal correlation is due to a mechanistic linkage, we have developed an extrachromosomal recombination assay that closely recapitulates DNA deletional class switch recombination. In this assay, the rate of recombination is measured between 24 and 48 hr posttransfection. We find that recombinants are generated in a switch sequence-dependent manner. Recombination occurs with a predominance within B-cell lines representative of the mature B cell stage and within a subset of pre-B-cell lines. Transcription stimulates the switch sequence-dependent recombination. Importantly, transcription activates recombination only when directed in the physiologic orientation but has no effect when directed in the nonphysiologic orientation. PMID- 7777561 TI - Identification of a plastid protein involved in vesicle fusion and/or membrane protein translocation. AB - Structural evidence has accumulated suggesting that fusion and/or translocation factors are involved in plastid membrane biogenesis. To test this hypothesis, we have developed an in vitro system in which the extent of fusion and/or translocation is monitored by the conversion of the xanthophyll epoxide (antheraxanthin) into the red ketocarotenoid (capsanthin). Only chromoplast membrane vesicles from red pepper fruits (Capsicum annuum) contain the required enzyme. Vesicles prepared from the mutant yellow cultivar are devoid of this enzyme and accumulate antheraxanthin. The fusion and/or translocation activity is characterized by complementation due to the synthesis of capsanthin and the parallel decrease of antheraxanthin when the two types of vesicles are incubated together in the presence of plastid stroma. We show that the extent of conversion is dependent upon an ATP-requiring protein that is sensitive to N-ethylmaleimide. Further purification and immunological analysis have revealed that the active factor, designated plastid fusion and/or translocation factor (Pftf), resides in a protein of 72 kDa. cDNA cloning revealed that mature Pftf has significant homology to yeast and animal (NSF) or bacterial (Ftsh) proteins involved in vesicle fusion or membrane protein translocation. PMID- 7777562 TI - RuvC protein resolves Holliday junctions via cleavage of the continuous (noncrossover) strands. AB - The RuvC protein of Escherichia coli resolves Holliday junctions during genetic recombination and the postreplicational repair of DNA damage. Using synthetic Holliday junctions that are constrained to adopt defined isomeric configurations, we show that resolution occurs by symmetric cleavage of the continuous (noncrossing) pair of DNA strands. This result contrasts with that observed with phage T4 endonuclease VII, which cleaves the pair of crossing strands. In the presence of RuvC, the pair of continuous strands (i.e., the target strands for cleavage) exhibit a hypersensitivity to hydroxyl radicals. These results indicate that the continuous strands are distorted within the RuvC/Holliday junction complex and that RuvC-mediated resolution events require protein-directed structural changes to the four-way junction. PMID- 7777564 TI - Low concentrations of diacylglycerol promote the binding of apolipophorin III to a phospholipid bilayer: a surface plasmon resonance spectroscopy study. AB - The binding of the exchangeable apolipoprotein apolipophorin III (apoLp-III) to an egg phosphatidylcholine bilayer as a function of the concentration of diacylglycerol (DG) in the bilayer was studied by surface plasmon resonance spectroscopy. At a DG concentration of 2 mol % in the bilayer, the binding of apoLp-III reached saturation. Under saturating conditions, apoLp-III forms a closely packed monolayer approximately 55 A thick, in which each molecule of protein occupies approximately 500 A2 at the membrane surface. These dimensions are consistent with the molecular size of the apoLp-III molecule determined by x ray crystallography, if apoLp-III binds to the bilayer with the long axis of the apoLp-III normal to the membrane surface. In the absence of protein, the overall structure of the lipid bilayer was not significantly changed up to 2.5 mol% DG. However, at 4 and 6 mol % DG, the presence of nonbilayer structures was observed. The addition of apoLp-III to a membrane containing 6 mol % DG promoted the formation of large lipid-protein complexes. These data support a two-step sequential binding mechanism for binding of apoLp-III to a lipid surface. The first step is a recognition process, consisting of the adsorption of apoLp-III to a nascent hydrophobic defect in the phospholipid bilayer caused by the presence of DG. This recognition process might depend on the presence of a hydrophobic sensor located at one of the ends of the long axis of the apoLp-III molecule but would be consolidated through H-bond and electrostatic interactions. Once primary binding is achieved, subsequent enlargement of the hydrophobic defect in the lipid surface would trigger the unfolding of the apolipoprotein and binding via the amphipathic alpha-helices. This two-step sequential binding mechanism could be a general mechanism for all exchangeable apolipoproteins. A possible physiological role of the ability of apoLp-III to bind to lipid structures in two orientations is also proposed. PMID- 7777565 TI - Mitochondrial DNA replication but no nuclear DNA replication during development of Dictyostelium. AB - Dictyostelium discoideum cells initiate development when nutrients are depleted. DNA synthesis decreases rapidly thereafter but resumes during late aggregation, only in prespore cells. This observation has been previously interpreted as indicating progression of prespore cells through the cell cycle during development. We show that developmental DNA replication occurs only in mitochondria and not in nuclei. We also show that the prestalk morphogen known as differentiation-inducing factor 1 can inhibit mitochondrial respiration. A model is proposed for cell type divergence, based on competition to become prespores, that involves mitochondrial replication in prespore cells and reduction of mitochondrial activity in prestalk cells. PMID- 7777563 TI - Rep protein of tomato yellow leaf curl geminivirus has an ATPase activity required for viral DNA replication. AB - The Rep protein of geminiviruses is the sole viral protein required for their DNA replication. The amino acid sequence of Rep protein contains an NTP binding consensus motif (P-loop). Here we show that purified Rep protein of tomato yellow leaf curl virus expressed in Escherichia coli exhibits an ATPase activity in vitro. Amino acid exchanges in the P-loop sequence of Rep causes a substantial decrease or loss of the ATPase activity. In vivo, mutant viruses carrying these Rep mutations do not replicate in plant cells. These results show that ATP binding by the Rep protein of geminiviruses is required for its function in viral DNA replication. PMID- 7777567 TI - Adaptive mutations in Escherichia coli as a model for the multiple mutational origins of tumors. AB - The cells in most tumors are found to carry multiple mutations; however, based upon mutation rates determined by fluctuation tests, the frequency of such multiple mutations should be so low that tumors are never detected within human populations. Fluctuation tests, which determine the cell-division-dependent mutation rate per cell generation in growing cells, may not be appropriate for estimating mutation rates in nondividing or very slowly dividing cells. Recent studies of time-dependent, "adaptive" mutations in nondividing populations of microorganisms suggest that similar measurements may be more appropriate to understanding the mutation origins of tumors. Here I use the ebgR and ebgA genes of Escherichia coli to measure adaptive mutation rates where multiple mutations are required for rapid growth. Mutations in either ebgA or ebgR allow very slow growth on lactulose (4-O-beta-D-galactosyl-D-fructose), with doubling times of 3.2 and 17.3 days, respectively. However, when both mutations are present, cells can grow rapidly with doubling times of 2.7 hr. I show that during prolonged (28 day) selection for growth on lactulose, the number of lactulose-utilizing mutants that accumulate is 40,000 times greater than can be accounted for on the basis of mutation rates measured by fluctuation tests, but is entirely consistent with the time-dependent adaptive mutation rates measured under the same conditions of prolonged selection. PMID- 7777566 TI - Yeast histone H3 and H4 N termini function through different GAL1 regulatory elements to repress and activate transcription. AB - Previous work has shown that N-terminal deletions of yeast histone H3 cause a 2- to 4-fold increase in the induction of GAL1 and a number of other genes involved in galactose metabolism. In contrast, deletions at the H4 N terminus cause a 10- to 20-fold decrease in the induction of these same GAL genes. However, H3 and H4 N-terminal deletions each decrease PHO5 induction only 2- to 4-fold. To define the GAL1 gene regulatory elements through which the histone N termini activate or repress transcription, fusions were made between GAL1 and PHO5 promoter elements attached to a beta-galactosidase reporter gene. We show here that GAL1 hyperactivation caused by the H3 N-terminal deletion delta 4-15 is linked to the upstream activation sequence. Conversely, the relative decrease in GAL1 induction caused by the H4N-terminal deletion delta 4-28 is linked to the downstream promoter which contains the TATA element. These data indicate that the H3 N terminus is required for the repression of the GAL1 upstream element, whereas the H4N terminus is required for the activation of the GAL1 downstream promoter element. PMID- 7777569 TI - Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells. AB - Granzyme (Gzm) B-deficient mice obtained by gene targeting were used to assess the role of Gzm B in the mechanisms used by natural killer (NK) and lymphokine activated killer (LAK) cells to destroy target cells. Gzm B-/- NK cells, LAK cells, and cytotoxic T lymphocytes (CTL) all are defective in their ability to rapidly induce DNA fragmentation/apoptosis in susceptible target cells. This defect can be partially corrected with long incubation times of effector and target cells. Moreover, Gzm B-/- NK cells (but not CTL or LAK cells) exhibit a defect in 51Cr release from susceptible target cells. This 51Cr release defect in Gzm B-deficient NK cells is also not overcome by prolonged incubation times or high effector-to-target cell ratios. We conclude that Gzm B plays a critical and nonredundant role in the rapid induction of DNA fragmentation/apoptosis by NK cells, LAK cells, and CTL. Gzm B may have an additional role in NK cells (but not in CTL or LAK cells) for mediating 51Cr release. PMID- 7777568 TI - Cytotoxic T-lymphocyte clones from different patients display limited T-cell receptor variable-region gene usage in HLA-A2-restricted recognition of the melanoma antigen Melan-A/MART-1. AB - To determine whether T-cell-receptor (TCR) usage by T cells recognizing a defined human tumor antigen in the context of the same HLA molecule is conserved, we analyzed the TCR diversity of autologous HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones derived from five patients with metastatic melanoma and specific for the common melanoma antigen Melan-A/MART-1. These clones were first identified among HLA-A2-restricted anti-melanoma CTL clones by their ability to specifically release tumor necrosis factor in response to HLA-A2.1+ COS-7 cells expressing this tumor antigen. A PCR with variable (V)-region gene subfamily-specific primers was performed on cDNA from each clone followed by DNA sequencing. TCRAV2S1 was the predominant alpha-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. beta-chain V-region usage was also restricted, with either TCRBV14 or TCRBV7 expressed by all but one clone. In addition, a conserved TCRAV2S1/TCRBV14 combination was expressed in four CTL clones from three patients. None of these V-region genes was found in a group of four HLA-A2-restricted CTL clones recognizing different antigens (e.g., tyrosinase) on the autologous tumor. TCR joining regions were heterogeneous, although conserved structural features were observed in the complementarity-determining region 3 sequences. These results indicate that a selective repertoire of TCR genes is used in anti-melanoma responses when the response is narrowed to major histocompatibility complex-restricted antigen specific interactions. PMID- 7777570 TI - Multiple loci govern the bone marrow-derived immunoregulatory mechanism controlling dominant resistance to autoimmune orchitis. AB - The existence of immunoregulatory genes conferring dominant resistance to autoimmunity is well documented. In an effort to better understand the nature and mechanisms of action of these genes, we utilized the murine model of autoimmune orchitis as a prototype. When the orchitis-resistant strain DBA/2J is crossed with the orchitis-susceptible strain BALB/cByJ, the F1 hybrid is completely resistant to the disease. By using reciprocal radiation bone marrow chimeras, the functional component mediating this resistance was mapped to the bone marrow derived compartment. Resistance is not a function of either low-dose irradiation- or cyclophosphamide (20 mg/kg)-sensitive immunoregulatory cells, but can be adoptively transferred by primed splenocytes. Genome exclusion mapping identified three loci controlling the resistant phenotype. Orch3 maps to chromosome 11, whereas Orch4 and Orch5 map to the telomeric and centromeric regions of chromosome 1, respectively. All three genes are linked to a number of immunologically relevant candidate loci. Most significant, however, is the linkage of Orch3 to Idd4 and Orch5 to Idd5, two susceptibility genes which play a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse. PMID- 7777571 TI - Blockade of T- and B-lymphocyte development by antibody to the gamma c subunit of the receptors for interleukins 2, 4, and 7. AB - Cytokines are important regulators of hematopoesis. Mutations in gamma c, which is a subunit shared by the receptors for interleukin (IL) 2, IL-4, and IL-7, have been causally associated with human X chromosome-linked severe combined immunodeficiency disease. This finding indicates a mandatory role for cytokine receptor signaling at one or more stages of lymphocyte development. To evaluate the cellular level at which gamma c is critical for lymphopoiesis, the effect of monoclonal antibodies to gamma c on the capacity of syngeneic bone marrow cells to reconstitute the hematopoietic compartment of lethally irradiated recipient mice was examined. We show that monoclonal antibody to gamma c blocked lymphocyte development at or before the appearance of pro-B cells and prior to or at the seeding of the thymus by precursor cells while erythromyeloid cell development was normal. These results suggest that one level of lymphocyte development that requires gamma c is a point in hematopoietic cell differentiation near the divergence of lymphopoiesis and erythromyelopoesis. PMID- 7777572 TI - A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system. AB - We have studied the functional consequences of a mutation in the epithelial Na+ channel that causes a heritable form of salt-sensitive hypertension, Liddle disease. This mutation, identified in the original kindred described by Liddle, introduces a premature stop codon in the channel beta subunit, resulting in a deletion of almost all of the C terminus of the encoded protein. Coexpression of the mutant beta subunit with wild-type alpha and gamma subunits in Xenopus laevis oocytes resulted in an approximately 3-fold increase in the macroscopic amiloride sensitive Na+ current (INa) compared with the wild-type channel. This change in INa reflected an increase in the overall channel activity characterized by a higher number of active channels in membrane patches. The truncation mutation in the beta subunit of epithelial Na+ channel did not alter the biophysical and pharmacological properties of the channel--including unitary conductance, ion selectivity, or sensitivity to amiloride block. These results provide direct physiological evidence that Liddle disease is related to constitutive channel hyperactivity in the cell membrane. Deletions of the C-terminal end of the beta and gamma subunits of rat epithelial Na+ channel were functionally equivalent in increasing INa, suggesting that the cytoplasmic domain of the gamma subunit might be another molecular target for mutations responsible for salt-sensitive forms of hypertension. PMID- 7777573 TI - Construction and characterization of a highly complex retroviral library for lineage analysis. AB - Replication-incompetent retroviral vectors encoding histochemical reporter genes have been used for studying lineal relationships in a variety of species. A crucial element in the interpretation of data generated by this method is the identification of sibling relationships, or clonal boundaries. The use of a library of viruses in which each member is unique can greatly facilitate this aspect of the analysis. A previously reported murine retroviral library containing about 80 members demonstrated the utility of the library approach. However, the relatively low number of tags in the murine library necessitated using low infection rates in order to give confidence in clonal assignments. To obviate the need for low infection rates, a far more complex library was created and characterized. The CHAPOL library was constructed such that each member encodes a histochemical reporter gene and has a DNA tag derived from a degenerate oligonucleotide pool synthesized to have a complexity of > 1 x 10(7). The library was tested after infection of cells in vitro or in vivo. The DNA tag from each histochemically labeled cell or clone of cells was recovered by PCR and sequenced for unambiguous identification. Three hundred and twenty tags have been identified after infection, and so far no tag has been seen to result from more than one independent infection. Thus, an equal distribution of inserts is suggested, and Monte Carlo analysis predicts a complexity of > 10(4) members. PMID- 7777574 TI - Deregulated expression of PAX5 in medulloblastoma. AB - Medulloblatoma is a pediatric brain tumor originating in the human cerebellum. A collection of 23 medulloblastomas was analyzed for expression of the developmental control genes of the PAX and EN gene families by RNase protection and in situ hybridization. Of all nine PAX genes investigated, only PAX5 and PAX6 were consistently expressed in most medulloblastomas (70 and 78% of all cases, respectively), as were the genes EN1 (57%) and EN2 (78%). EN1, EN2, and PAX6 genes were also expressed in normal cerebellar tissue, and their expression in medulloblastoma is consistent with the hypothesis that this tumor originates in the external granular layer of the developing cerebellum. PAX5 transcripts were, however, not detected in the neonatal cerebellum, indicating that this gene is deregulated in medulloblastoma. In the desmoplastic variant of medulloblastoma, PAX5 expression was restricted to the reticulin-producing proliferating tumor areas containing undifferentiated cells; PAX5 was not expressed in the reticulin free nonproliferating islands undergoing neuronal differentiation. These data suggest that deregulated expression of PAX5 correlates positively with cell proliferation and inversely with neuronal differentiation in desmoplastic medulloblastoma. PMID- 7777575 TI - DNA synthesis and topoisomerase inhibitors increase transduction by adeno associated virus vectors. AB - Viral vectors based on adeno-associated virus (AAV) preferentially transduce cells in S phase of the cell cycle. We recently found that DNA-damaging agents increased the transduction of nondividing cells. However, the optimal concentrations were toxic to cells. Here we show that the transduction of normal human fibroblasts by AAV vectors is increased by prior exposure to DNA synthesis inhibitors, such as aphidicolin or hydroxyurea, and topoisomerase inhibitors, such as etoposide or camptothecin. Transduction efficiencies could be increased > 300-fold in stationary cultures at concentrations that did not affect cell viability or proliferative potential. Both S-phase and non-S-phase cells were affected, suggesting that cellular functions other than replicative DNA synthesis may be involved. Applying these methods to gene transfer protocols should improve prospects for gene therapy by AAV vectors. PMID- 7777576 TI - The carboxyl-terminal domain of the p53 protein regulates sequence-specific DNA binding through its nonspecific nucleic acid-binding activity. AB - The murine p53 protein contains two nucleic acid-binding sites, a sequence specific DNA-binding region localized between amino acid residues 102-290 and a nucleic acid-binding site without sequence specificity that has been localized to residues 364-390. Alternative splicing of mRNA generates two forms of this p53 protein. The normal, or majority, splice form (NSp53) retains its carboxyl terminal sequence-nonspecific nucleic acid-binding site, which can negatively regulate the sequence-specific DNA-binding site. The alternative splice form of p53 (ASp53) replaces amino acid residues 364-390 with 17 different amino acids. This protein fails to bind nucleic acids nonspecifically and is constitutive for sequence-specific DNA binding. Thus, the binding of nucleic acids at the carboxyl terminus regulates sequence-specific DNA binding by p53. The implications of these findings for the activation of p53 transcriptional activity following DNA damage are discussed. PMID- 7777577 TI - Somatodendritic expression of an immediate early gene is regulated by synaptic activity. AB - Trans-synaptic activation of gene expression is linked to long-term plastic adaptations in the nervous system. To examine the molecular program induced by synaptic activity, we have employed molecular cloning techniques to identify an immediate early gene that is rapidly induced in the brain. We here report the entire nucleotide sequence of the cDNA, which encodes an open reading frame of 396 amino acids. Within the hippocampus, constitutive expression was low. Basal levels of expression in the cortex were high but can be markedly reduced by blockade of N-methyl-D-aspartate receptors. By contrast, synaptic activity induced by convulsive seizures increased mRNA levels in neurons of the cortex and hippocampus. High-frequency stimulation of the perforant path resulted in long term potentiation and a spatially confined dramatic increase in the level of mRNA in the granule cells of the ipsilateral dentate gyrus. Transcripts were localized to the soma and to the dendrites of the granule cells. The dendritic localization of the transcripts offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events. PMID- 7777578 TI - Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila. AB - From an extract of Drosophila melanogaster head homogenates, a membrane fraction can be isolated that has the same sedimentation properties as vertebrate synaptic vesicles and contains Drosophila synaptotagmin. The fraction disappears from homogenates of temperature-sensitive (ts) mutant shibire(ts1) (shi(ts1)) flies paralyzed by exposure to non-permissive temperatures, and reappears on return to permissive temperatures. Since reversible, temperature-dependent depletion of synaptic vesicles is known to occur in shibire(ts1) flies, we conclude that the fraction we have identified contains synaptic vesicles. We have examined the fate of synaptic vesicle membrane proteins in shibire flies at nonpermissive temperatures and found that all of these vesicle antigens are transferred to rapidly sedimenting membranes and codistribute with a plasma membrane marker by both glycerol velocity and metrizamide density sedimentation and by confocal microscopy. Three criteria were used to establish that other neuron-specific antigens--neuronal synaptobrevin and cysteine-string proteins--are legitimate components of synaptic vesicles: cosedimentation with Drosophila synaptotagmin, immunoadsorption, and disappearance of these antigens from the vesicle fractions in paralyzed shibire flies. PMID- 7777579 TI - Phosphatidylinositol 3-kinase signals activation of p70 S6 kinase in situ through site-specific p70 phosphorylation. AB - The p70 S6 kinase is activated by insulin and mitogens through multisite phosphorylation of the enzyme. One set of activating phosphorylations occurs in a putative autoinhibitory domain in the noncatalytic carboxyl-terminal tail. Deletion of this tail yields a variant (p70 delta CT104) that nevertheless continues to be mitogen regulated. Coexpression with a recombinant constitutively active phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) gives substantial activation of both full-length p70 and p70 delta CT104 but not Rsk. Activation of p70 delta CT104 by PI 3-kinase and inhibition by wortmannin are each accompanied by parallel and selective changes in the phosphorylation of p70 Thr-252. A Thr or Ser at this site, in subdomain VIII of the catalytic domain just amino-terminal to the APE motif, is necessary for p70 40S kinase activity. The inactive ATP binding site mutant K123M p70 delta CT104 undergoes phosphorylation of Thr-252 in situ but does not undergo direct phosphorylation by the active PI 3-kinase in vitro. PI 3-kinase provides a signal necessary for the mitogen activation of the p70 S6 kinase, which directs the site-specific phosphorylation of Thr-252 in the p70 catalytic domain, through a distinctive signal transduction pathway. PMID- 7777580 TI - Insertional mutagenesis and marker rescue in a protozoan parasite: cloning of the uracil phosphoribosyltransferase locus from Toxoplasma gondii. AB - Nonhomologous integration vectors have been used to demonstrate the feasibility of insertional mutagenesis in haploid tachyzoites of the protozoan parasite Toxoplasma gondii. Mutant clones resistant to 5-fluorouracil were identified at a frequency of approximately 10(-6) (approximately 2 x 10(-5) of the stable transformants). Four independent mutants were isolated, all of which were shown to lack uracil phosphoribosyl-transferase (UPRT) activity and harbor transgenes integrated at closely linked loci, suggesting inactivation of the UPRT-encoding gene. Genomic DNA flanking the insertion point (along with the integrated vector) was readily recovered by bacterial transformation with restriction-digested, self ligated total genomic DNA. Screening of genomic libraries with the recovered fragment identified sequences exhibiting high homology to known UPRT-encoding genes from other species, and cDNA clones were isolated that contain a single open reading frame predicted to encode the 244-amino acid enzyme. Homologous recombination vectors were exploited to create genetic knock-outs at the UPRT locus, which are deficient in enzyme activity but can be complemented by transient transformation with wild-type sequences--formally confirming identification of the functional UPRT gene. Mapping of transgene insertion points indicates that multiple independent mutants arose from integration at distinct sites within the UPRT gene, suggesting that nonhomologous integration is sufficiently random to permit tagging of the entire parasite genome in a single transformation. PMID- 7777582 TI - delta 9-Tetrahydrocannabinol, cytokines, and immunity to Legionella pneumophila. AB - The major psychoactive component of marijuana, delta 9-tetrahydrocannabinol (THC), has been shown to suppress the functions of various immune cells. However, the relationship of these findings to THC-induced suppression of host resistance to infection has not been firmly established. In this report, we review the literature concerning THC's effects on cytokine production and resistance to infection with Legionella pneumophila (Lp). Recent reports have linked THC induced immunomodulation with drug-induced modulation of the cytokine network. Specifically, THC in vivo suppresses interferon (IFN) production while in vitro modulates the production of tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-2 receptor (IL-2R). These results suggested that THC treatment might alter host immunity by disrupting the cytokine network. Immunity and resistance to infection with Lp depends upon the activation of killer cells and the stimulation of the cytokine network. THC injection into rodents was observed to augment acute phase cytokine mobilization in response to a primary Lp infection; on the other hand, the drug suppressed the development of protective immunity and resistance to secondary Lp infection by causing a change in the profile of T helper cell cytokines produced by Th1 and Th2 cells. Thus, it appears that THC injection suppresses resistance to Lp infection by disrupting the cytokine network. Regarding the molecular mechanisms of these effects of THC, data is reviewed concerning the role of cannabinoid receptors (CR) in cells of the immune system. In summary, the literature to date supports the role of THC as an immunomodulator capable of suppressing resistance to infection through mechanisms involving alteration of the cytokine network. The role of CR receptors in these events has yet to be determined. PMID- 7777583 TI - Diet, autoimmunity, and insulin-dependent diabetes mellitus: a controversy. AB - Insulin-dependent diabetes mellitus (IDDM) is a serious disorder comprising approximately 10% of the total diabetic population. The majority of the genetic mutations that result in the phenotypic expression of the IDDM genotype are in the immune system. In some, the disease arises as a consequence of a viral infection. While some viruses target the islet beta cell and destroy it, other viruses induce changes in the antigen recognition system such that the affected individual appears to have autoimmune disease. Autoimmune-IDDM results from one or more mutations in the immune system that result in a failure to distinguish self antigens from foreign antigens. As a result, the beta cells of the endocrine pancreas are destroyed. This review addresses the issue of whether dietary factors, in particular, milk protein, can initiate the autoimmune process. Based on the population studies available in the literature, the conclusion is reached that, while antibodies to milk proteins can be found in the patient with autoimmune diabetes mellitus, these antibodies were probably elicited by a closely related protein (antigen mimicry). Because one of the features of autoimmune disease is a loss of antibody specificity, cross-reactivity occurs and appears to identify milk protein(s) as the antigen. PMID- 7777581 TI - Endogenous mutagenesis by an insertion sequence element identifies Aeromonas salmonicida AbcA as an ATP-binding cassette transport protein required for biogenesis of smooth lipopolysaccharide. AB - Analysis of an Aeromonas salmonicida A layer-deficient/O polysaccharide-deficient mutant carrying a Tn5 insertion in the structural gene for A protein (vapA) showed that the abcA gene immediately downstream of vapA had been interrupted by the endogenous insertion sequence element ISAS1. Immunoelectron microscopy showed that O polysaccharides did not accumulate at the inner membrane-cytoplasm interface of this mutant. abcA encodes an unusual protein; it carries both an amino-terminal ATP-binding cassette (ABC) domain showing high sequence similarity to ABC proteins implicated in the transport of certain capsular and O polysaccharides and a carboxyl-terminal potential DNA-binding domain, which distinguishes AbcA from other polysaccharide transport proteins in structural and evolutionary terms. The smooth lipopolysaccharide phenotype was restored by complementation with abcA but not by abcA carrying site-directed mutations in the sequence encoding the ATP-binding site of the protein. The genetic organization of the A. salmonicida ABC polysaccharide system differs from other bacteria. abcA also differs in apparently being required for both O-polysaccharide synthesis and in energizing the transport of O polysaccharides to the cell surface. PMID- 7777584 TI - Chronic energy restriction versus energy cycling and mammary tumor promotion. AB - Chronic energy restriction significantly inhibits mammary tumor promotion in rodents. The present work studied the effect of short-term, intermittent energy restriction or energy cycling on mammary tumor promotion since this feeding paradigm mimics the dieting habits of humans. Female Sprague-Dawley rats were given 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age (5 mg ig). One week later, rats were randomly divided into three dietary groups. One group was fed ad libitum throughout the study (AL), another (ER) was fed 40% fewer calories than the AL group, and a third, energy-cycled group (EC) was fed in repeated cycles of 2 days of feeding at a level comparable to that of AL rats followed by 2 days of 40% energy restriction. At 10 weeks post-DMBA, the mammary tumor incidences in the AL and EC groups were the same, but incidence in the ER group was significantly lower. A second experiment examined serum levels of three hormones thought to play a role in mammary tumorigenesis. After 12 or 24 days on diet, ER rats had lower insulin levels compared with the other groups. Serum insulin levels in AL and EC rats were the same. After 24 days on diet, estradiol levels were significantly lower and corticosterone levels higher in the ER and EC groups compared with the AL group. Although energy cycling is a type of energy restriction that lowers overall weight gain and energy intake, it does not inhibit mammary tumor promotion as does chronic energy restriction. These data also suggest that feed efficiency and serum insulin levels correlate with susceptibility to mammary tumor promotion. PMID- 7777585 TI - Luteinizing hormone response to N-methyl-D, L-aspartic acid in the presence of physiological estradiol concentrations: influence of age and the ovary. AB - We have previously reported that the pituitary of intra-atrially cannulated old female C57BL/6J mice is as capable of responding to a GnRH challenge as is that of young females (10). We have observed elevated luteinizing hormone (LH) levels in ovariectomized (OVX) intra-atrially cannulated mice. Sustained physiologic levels of estradiol (E2) for 6 days suppressed circulating LH to intact levels. However, in that model, a bolus of E2 following E2 priming was unable to elicit an LH surge (Joshi et al., unpublished findings). The present studies were designed to examine: first, whether GnRH neurons are competent to release GnRH in the presence of tonic physiologic levels of E2 and, second, whether either age or the ovary can influence GnRH neuronal responsiveness. The N-methyl-D, L-aspartic acid (NMA)-evoked GnRH response was assessed indirectly by measuring LH in two groups of OVX C57BL/6J mice: short-term OVX (S-OVX) (1 week) mice were either prepubertal (5 weeks), postpubertal (10 weeks), young (5 months), middle aged (12 months), or old (24 months). Long-term OVX (L-OVX) mice were either young (5 months), or old (24 months) and OVX at puberty; middle-aged L-OVX mice were OVX at 8 months and examined at 12 months of age. Animals were administered physiologic levels of E2 by subcutaneous silastic capsule for 1 week before testing. LH secretion was inhibited by E2 in S-OVX mice of all ages. In no case did NMA overcome this inhibition in E2 primed S-OVX females. E2 also inhibited LH secretion in L-OVX mice of all ages, but NMA was able to overcome the E2 inhibition of LH secretion in L-OVX mice (young: 0.5 +/- 0.1, 0.84 +/- 0.19 ng/ml, first and second challenge, respectively; middle-aged: 0.46 +/- 0.1, 1.08 +/- 0.16 ng/ml; and old: 1.44 +/- 0.19, 0.99 +/- 0.27 ng/ml). This last effect was independent of animal maturity at the time of OVX or animal age at the time of experiment. These findings suggest that although the ovaries in the 24-month old S-OVX mice had not produced enough E2 to alter the vaginal cytology for 2 +/- 0.5 months before the experiment, the ovarian modulation of the inhibitory effect of E2 on NMA-induced LH secretion was still present. The nature of the ovarian factor(s) modulating this effect is unknown.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777586 TI - Immunoreactive insulin in rat salivary glands and its dependence on age and serum insulin levels. AB - The major salivary glands of adult rodents contain immunoreactive insulin (IRI). To determine if the concentration of IRI in salivary glands is modulated by the level of serum insulin, insulin immunoreactivity in the parotid and submandibular glands of male rats at different ages (sucklings, pubescent, mature, and elderly) was assayed and compared with corresponding serum insulin concentrations. Salivary glands from suckling rats contained 94 ng/g (wet weight) insulin, which is 1.6 times higher than the level in pubescent rats, and about 10 times higher than levels in mature and elderly rats. No direct relationship between salivary gland content and serum IRI levels was indicated by the data. In an attempt to increase insulin levels in serum, insulin-secreting pancreatic islet adenomas were induced in young male rats by injecting streptozotocin (an islet tumor inducing drug) with nicotinamide (which reduces the drug's beta-cell cytotoxicity). The mean insulin content of salivary glands from drug-treated rats that had not yet expressed tumors was no higher than controls. After the development of visible tumors of pancreatic islet tissue, however, salivary gland IRI was markedly elevated, reaching 40 times control levels, whereas serum insulin, and the immunoreactive insulin content of two insulin-sensitive tissues (vis. hepatic, adipose), were elevated only 2-fold. Examination of histologic sections of the parotid and submandibular glands from drug-treated animals revealed no evidence for the formation of salivary tumors. The data indicate that salivary gland insulin content (i) is age-related, being highest in neonates and declining thereafter, (ii) is generally identical in parotid and submandibular glands at a given age, and (iii) is not modulated solely by the animal's serum insulin concentration. These results are discussed in regard to the possible sources of insulin detected in the major salivary glands. PMID- 7777587 TI - Establishment and characterization of human fetal liver epithelial cell line transfected with SV40 T antigen. AB - The aim of the present study was to establish a stable cell line useful for the study of growth and differentiation of human fetal liver cells. We have established an immortalized human fetal liver cell line (designated NFL/T) by transfection with simian virus 40 (SV40) large T antigen, without any culture crisis. The cells showed growth properties similar to normal cells, including density-dependent cell growth. Electron microscopy demonstrated liver-specific differentiated morphological properties. Moreover, positive albumin and cytokeratin 7 production was detected immunologically. Thus, the NFL/T cell line is less transformed than the other fetal liver cell lines established by this method, and might be useful to study the growth and differentiation of human fetal liver cells. PMID- 7777588 TI - Investigation of intracellular signals mediating the anti-apoptotic action of prolactin in Nb2 lymphoma cells. AB - Studies were undertaken to identify intracellular mediators of prolactin inhibition of glucocorticoid-induced apoptosis in Nb2 lymphoma cells. A short term assay was implemented that quantitates fragmented DNA released from the genome by reaction with diphenylamine. Induction and inhibition of internucleosomal DNA cleavage (indicative of apoptosis) was verified by agarose gel electrophoresis of extracted cellular DNA. Synchronized Nb2 cells (G0/G1) exhibited increased DNA fragmentation after 4-hr incubation with dexamethasone (DEX) (25-100 nM) which was inhibited by ovine prolactin (oPRL) (0.1-1 ng/ml), the glucocorticoid receptor antagonist, RU486 (500 nM), and the nuclease inhibitor, aurintricarboxylic acid (100 microM). Signals previously implicated in prolactin induction of mitogenesis in Nb2 cells were investigated for their role in prolactin inhibition of apoptosis including: protein kinase C activation, arachidonic acid metabolism, polyamine production, tyrosine phosphorylation, and extracellular calcium. Protein kinase C agonists, phorbol-12-myristate-13 acetate, and 1,2-dioctanoyl-sn-glycerol, +/- the calcium ionophore, A23187 (200 nM), did not mimic oPRL inhibition of DEX-induced DNA fragmentation. Protein kinase C inhibitors, gossypol and quercetin, did not block prolactin action. Arachidonic acid did not mimic prolactin protection against DEX-induced DNA fragmentation. Inhibitors of arachidonic acid metabolism, 5,8,11,14 eicosatetraynoic acid, nordihydroguaiaretic acid, and indomethacin did not block prolactin action. The polyamine, spermine, inhibited DEX-induced DNA fragmentation at 1.5 to 2.5 mM. However, inhibition of polyamine synthesis with alpha-difluoromethyl ornithine or methylglyoxal bis(guanylhydrazone) did not inhibit prolactin action. Prolactin action was not blocked by inhibitors of tyrosine kinase activation, genistein and tyrphostin-47. On the other hand, pervanadate, a potent tyrosine phosphatase inhibitor, consistently inhibited DEX induced DNA fragmentation. Prolactin action and DEX-induced apoptosis both occurred in calcium-free PBS. In summary, protein kinase C activation and eicosanoid production do not appear to mediate this prolactin action. Although spermine could block DNA fragmentation, blockade of the polyamine cascade did not inhibit prolactin action, suggesting that polyamines do not mediate this prolactin effect. While inhibitors of tyrosine kinase activation did not block prolactin action, tyrosine phosphatase inhibition in the presence of basal tyrosine kinase activity mimicked prolactin action, suggesting tyrosine phosphorylation participation in the anti-apoptotic effect. Extra-cellular calcium was not required for prolactin or DEX action. PMID- 7777590 TI - Transferrin reduces the production of soluble transferrin receptor. AB - The effect of homologous diferric transferrin from which contaminating transferrin receptor has been removed by monoclonal antibody affinity chromatography on soluble transferrin receptor concentrations was studied in K562 cells and HL60 cells in culture. Diferric transferrin in K562 cells caused a dose dependent decrease in cellular receptor expression, a dose-dependent increase in cellular ferritin content, and a reduction in soluble receptor concentration which was of greater proportional magnitude than the reduction in cell receptor content. In HL60 cells, while there was a dose-dependent increase in cellular ferritin, cellular receptor content was relatively unaffected, while there was a consistent reduction in soluble receptor concentration. In both cells, the inhibitory effect of diferric transferrin on soluble receptor concentration was evident as early as 3 hr into the incubation. Apotransferrin, by contrast, did not reduce soluble receptor concentration. While elemental iron was capable of producing similar changes in cellular receptor and ferritin content, it had no inhibitory effect on proportional soluble receptor content. Studies employing other proteins, including human and bovine serum albumin, human lactoferrin, and rat ferritin, had no inhibitory effect on soluble receptors concentration, thus confirming the specificity of the findings. Control studies excluded an assay artifact as the explanation for the current findings. Prior contrary reports appear completely explained by the combination of soluble transferrin receptor contaminating the transferrin employed for study and a systematic difference in the assays employed between free and transferrin-bound receptor. PMID- 7777589 TI - Gastrointestinal vasculitis in autoimmune-prone (NZW X BXSB)F1 mice: association with anticardiolipin autoantibodies. AB - Gastrointestinal vasculitis is a fatal aspect of systemic lupus erythematosus. Whether lupus-prone strains of mice develop gastrointestinal vasculitis, and whether it is accompanied by elevated titres of anticardiolipin autoantibody is not known. Lupus-prone (NZW X BXSB)F1 (W/BF1) mice, and other strains were examined immunohistologically. Levels of anticardiolipin autoantibody and circulating immune complexes were determined by microELISA. Reciprocal haploidentical marrow transplantations between W/BF1 and autoimmune-resistent B6C3F1 mice were made. Young adult W/BF1 mice had the highest incidence of gastrointestinal vasculitis (61%), and the highest mean titre of anticardiolipin autoantibody. Lesions consisted of subintimal fibrinoid degeneration in arterioles of the duodenum, jejunum and ileum, and were prevented, or alternatively induced by reciprocal marrow transplantations between W/BF1 and B6C3F1 mice. Mice engrafted with W/BF1 marrow which developed vasculitis had higher titres of anticardiolipin autoantibodies than engrafted mice free of vasculitis (P < 0.005). This represents the first report of gastrointestinal vasculitis as an aspect of systemic autoimmunity in lupus-prone mice. The concurrent elevation of anticardiolipin autoantibody and development of vasculitis suggests that anticardiolipin autoantibodies, and their proposed thrombogenic and vascular injury consequences, contribute to development of microvasculitis in lupus-prone mice. PMID- 7777591 TI - Leg design and jumping technique for humans, other vertebrates and insects. AB - Humans, bushbabies, frogs, locusts, fleas and other animals jump by rapidly extending a pair of legs. Mathematical models are used to investigate the effect muscle properties, leg design and jumping technique have on jump height. Jump height increases with increased isometric force exerted by leg muscles, their maximum shortening speeds and their series compliances. When ground forces are small multiples of body mass (as for humans), countermovement and catapult jumps are about equally high, and both are much better than squat jumps. Vertebrates have not evolved catapult mechanisms and use countermovement jumps instead. When ground forces are large multiples of body mass, catapult jumps (as used by locusts and fleas) are much higher than the other styles of jump could be. Increasing leg mass reduces jump height, but the proximal-to-distal distribution of leg mass has only a minor effect. Longer legs make higher jumps possible and additional leg segments, such as the elongated tarsi of bushbabies and frogs, increase jump height even if overall leg length remains unchanged. The effects of muscle moment arms that change as the leg extends, and of legs designed to work over different ranges of joint angle, are investigated. PMID- 7777593 TI - 23rd Annual Meeting of the American Society for Photobiology. Washington, D.C., June 17-22, 1995. Abstracts. PMID- 7777594 TI - Mating in the monogamous male: behavioral consequences. AB - In monogamous mammals, males typically show selective affiliation with a single mate, high levels of paternal care, and aggression towards conspecifics to protect male and offspring. We have previously described how selective aggression and affiliation increase after mating in the male prairie vole, Microtus ochrogaster. The current studies further explored the behavioral changes that follow mating in the male of this species. The first set of experiments tested males on several behavioral measures after 24 h of either mating, social (but not sexual) exposure, or no social contact. After 24 h of mating, but not after the other two conditions, aggression and affiliation (partner preference) increased as previously reported. In addition, mated animals showed increased exploration of the open arms of a plus maze, consistent with decreased fearfulness. There were no group differences in paternal behavior (which was high in all three conditions) or analgesia (assessed by tail flick latency). To determine the minimum amount of mating necessary for the induction of aggression, males were tested in a resident-intruder paradigm after 1,6, or 24 h of mating. Although 1 h of mating was associated with a transient increase in the frequency of threats and attacks, the full spectrum of enduring aggression was observed only in the males given 24 h of mating. In a final experiment, the behavioral consequences of mating were studied in males of the closely related montane vole (Microtus montanus) which does not pair bond. Males of this nonmonogamous vole species did not show increased aggression, partner preference, or alterations in plus maze exploration following 24 h of mating. These results demonstrate the importance of prolonged mating for the induction of pair bonding in the monogamous male and they suggest that increases in aggression and affiliation are associated with decreased fearfulness in pair bonded males. PMID- 7777592 TI - Molecular genetic variation and individual survival during population crashes of an unmanaged ungulate population. AB - Theoretical models of the effect of population bottlenecks on genetic variation assume that individuals are removed at random from the population. We investigated this assumption in a naturally regulated, unstable population of Soay sheep (Ovis aries). During rapid population declines or 'crashes', individuals were not removed at random with respect to genotype: we found associations between individual survival and certain genotypes at five polymorphic protein or microsatellite DNA loci (Ada, Got, Tf, MAF18 and OPACAP). Some loci appeared to show simple associations with survival whereas others had more complex interactions with crash year or age: all displayed different patterns of association between the sexes. Simple overdominance was not a general feature of our data; it seems likely that fluctuating selecting, countervailing selection in different fitness components or frequency-dependent selection may explain the pattern and complexity of the associations shown at different loci. Our study cannot distinguish between selection acting at these loci or at other, closely linked loci. However, our empirical study implies that the molecular genetic outcome of population bottlenecks in natural populations does not always follow theoretical expectations based on the random removal of genotypes. Bottlenecks in which individuals are removed at random are distinct from bottlenecks in which there is scope for selection via non-random survival of individuals. PMID- 7777595 TI - Ontogenetic development and pentylenetetrazol seizure thresholds in rats. AB - Ontogenetic differences in seizure thresholds to pentylenetetrazol (PTZ) were examined in young, developing rats (ages: 10, 18, 28, and 60 days). A subconvulsive dose of PTZ (15 mg/kg IP) was administered every 10 min and the occurrence of partial and full (clonic tonic) seizures was noted. Ten day old pups displayed complete seizures more rapidly than any of the other groups (p < .01) without any behavioral indication of going through the partial stages. Among 18 day old pups the development of early seizure stages was followed rapidly by the full seizure, while in the weaned groups the early seizure stages tended to persist much longer before the appearance of the full generalized convulsion. The preweanling rat's immature brain seems less able to suppress PTZ induced generalized convulsions compared to the brain of the older rats. PMID- 7777596 TI - Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning. AB - Basal and stress-induced pituitary-adrenocortical (PA) and sympathetic adrenomedullary (SAM) function was investigated in rats exposed to chronic intermittent cold stress (4 degrees C for 4 h a day for 21 days; CHR). We found that basal plasma levels of corticosterone (B), corticosteroid-binding-globulin, ACTH, epinephrine (E) and norepinephrine (NE) were similar in CHR and control (CTL) animals. In contrast, activity of the adrenal catecholamine-synthesizing enzyme tyrosine hydroxylase, but not phenylethanolamine-N-methyl transferase, was significantly elevated in CHR compared to CTL. Following exposure to a heterotypic stressor (20 min restraint), plasma levels of B were significantly higher in CHR than CTL, but the stress-induced levels of E and NE were not different between groups. These data suggest that, although basal PA function is not altered by exposure to chronic intermittent cold stress, components of the SAM system are affected by this paradigm, and that co-ordinate facilitation of both PA and SAM responses to a novel stressor is not a necessary consequence of exposure to chronic intermittent stress. PMID- 7777597 TI - Priming of locomotor initiation by electrical stimulation in the hypothalamus and preoptic region in the anesthetized rat. AB - Electrical stimulation at a locomotor site can prime (i.e., shorten the latency to initiate) stepping elicited by subsequent stimulation of the same or a different site. We tested for the priming effect in representative sites along the medial forebrain bundle, and determined if its magnitude showed regional differences. Rats (n = 20) were anesthetized with Nembutal and held in a stereotaxic apparatus over a wheel. Stepping was detected by accelerometers attached to the hindlimbs. Priming and test trains of stimulation (0.5-ms cathodal pulses, 50 Hz, 25-75 microA, 7-9-s train duration) separated by 20 s were delivered every 90 s. When the priming and test stimulations were applied to the same site, the priming effects were similar along the entire extent of the medial forebrain bundle. When the priming and test sites were different, the priming effect depended on their relative positions. Anterior stimulation primed posterior sites at magnitude comparable to those produced by stimulating the same posterior site. Posterior stimulation primed anterior sites at a level half of that produced by stimulation of the same anterior site. This pattern was found for priming and test sites that were ipsilateral and contralateral. Priming is a general and robust phenomenon with properties that may be useful for studying locomotor initiation pathways. PMID- 7777598 TI - Impact of differential housing on humoral immunity following exposure to an acute stressor in rats. AB - The purpose of this study was to examine the effect of differential housing on humoral immunity following exposure to an acute stressor. Forty male Sprague Dawley adult rats were randomly assigned to either a singly housed or group housed (five rats/cage) condition. Approximately 2 weeks after the start of the study, all animals were immunized with 1 ml of a 10% suspension of sheep red blood cells (SRBC) in saline. After the injections, half of the animals from each housing condition were subjected to an acute stressor (forced swim, 60 min/day for 3-5 days). Animals exposed to the acute stressor displayed adrenal gland hypertrophy and reduced thymus and spleen weights compared to the unstressed (control) animals. Both behavioral stimuli (housing and forced swim) demonstrated no effect on antibody production to SRBC. However, singly housed animals showed an increase in lymphocyte percentage, and corticosterone and glucose levels regardless of subsequent exposure to acute stress. Within a treatment condition, there were no significant correlations between the immune and endocrine measures. It was concluded that reduced social contact (i.e., individual housing) with subsequent exposure to an acute stressor does not appear to inhibit immunological responsiveness to an antigen. PMID- 7777599 TI - Effects of naloxone on oxygen consumption and ventilation in awake golden Syrian hamsters. AB - Endogenous opioids are known to inhibit chemoreception and ventilatory control. The opioid antagonist naloxone stimulates ventilation by removing this inhibition. To study whether the effects of opiate receptor antagonism are mediated by a central or a peripheral mechanism, we administered equal doses of naloxone hydrochloride (NHCl, an agent that crosses the blood-brain barrier) and naloxone methiodide (NM, an agent that does not cross the blood-brain barrier) to awake golden Syrian hamsters. Both naloxone preparations significantly increased the oxygen consumption (46% for NHCl and 90% for NM) in these animals relative to saline. Naloxone hydrochloride, but not NM, stimulated ventilation (30%) and tidal volume (34%) when the animal was subjected to a hypercapnic challenge, predominantly sensed in the brain. In contrast, both naloxones stimulated ventilation by 52% compared to saline treatment when the hamsters were exposed to a hypoxic challenge, predominantly sensed peripherally. These results suggest that endogenous opioids modulate both central and peripheral chemoreception in the hamster. PMID- 7777600 TI - Mineral content of the diet alters sucrose-induced obesity in rats. AB - The effects of dietary mineral levels on caloric intake, nutrient choice, body weight, adipose tissue weight, interscapular brown adipose tissue (IBAT) weight, and thermogenic capacity, and plasma insulin and glucose levels were examined in adult male Sprague-Dawley rats. In Experiments 1 and 2, rats were fed a purified diet with zinc (Zn), chromium (Cr), and selenium (Se) added, or the same diet without the addition of these minerals. In Experiment 3, the effects of Zn and Cr were examined separately. In all experiments, half of the rats in each diet group were given a 32% sucrose solution in addition to their standard diet and water. Rats given sucrose consumed more calories and gained more weight than rats not given sucrose. However, mineral levels altered the effects of sucrose on these measures. Added minerals increased percent sucrose intake, reduced weight gain and feed efficiency, increased GDP binding in IBAT mitochondria, improved glucose tolerance, and reduced plasma insulin levels. The reduction in weight gain and increased feed efficiency found when Zn alone was added to the diet was independent of sucrose condition. In comparison, the alterations observed in these measures when Cr alone was added to the diet varied as a function of sucrose availability. PMID- 7777601 TI - Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory. AB - Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4 month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels. PMID- 7777603 TI - High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. AB - This study was designed to examine the interaction of pregnancy and dietary fat on pregnancy outcome and offspring metabolism in rats. Wistar rats were divided into four groups: HF (40% fat by weight) feeding and pregnant (HFP, n = 15); HF nonpregnant control (HFNP, n = 10); control diet (4.5% fat) and pregnant (CHP, n = 12); and control diet nonpregnant (CHNP, n = 10). Rats were fed the same diets throughout gestation and lactation and were sacrificed at weaning. Litter size was kept at six pups with extra pups killed at birth. HF-fed dams had significantly less caloric intake than control counterparts. HFP had similar body weight changes as CHP during gestation and lactation, whereas HFNP had significantly higher weight and fat content than CHNP. There was no difference in pup's birth weight. However, significantly more HF dams cannibalized their pups. Newborns delivered to HF-fed dams had higher insulin/glucose ratios than CH pups. HFP weanlings weighed more, had more body fat (%), higher liver weight, liver lipid content, and higher blood glucose and triglyceride levels than CHP weanlings. The long-term effects of these metabolic abnormalities need to be further examined. PMID- 7777602 TI - Gender, dietary restraint, and smoking's influence on hunger and the reinforcing value of food. AB - Smoking may enhance satiety following meal consumption, thereby reducing subsequent eating (i.e., between-meal snacks), especially in women high in dietary restraint. Female smokers (n = 20, 10 high and 10 low restraint) and male smokers (n = 10) participated in two sessions, involving overnight abstinence from food and smoking (smoking abstinence day) or from food only (smoking day), in a within-subjects design. The reinforcing value of food was determined by the number of responses made to obtain food reinforcers (100-kcal snack portions) vs. money using a concurrent schedules computer task. Subjects were given a small caloric load on each day followed by access to food vs. money. On the smoking day, subjects were allowed to smoke every 30 min during the session as well as ad lib before the session. Self-reported hunger was also assessed upon arrival (after fasting) and following the caloric load during each session. Results indicated no effect of smoking on initial hunger rating, after fasting, but hunger ratings following the caloric load declined significantly more during smoking vs. abstinence days for all subjects, consistent with an enhancement of postmeal satiety due to smoking. There was no overall main effect of smoking on food-reinforced responding. However, responding for food was significantly less during the smoking vs. abstinence days for high-restraint females only and not for low-restraint females or for males. These findings indicate that smoking's acute influence on reducing food intake does not reflect a broad gender difference but may be specific to dietary restraint. PMID- 7777605 TI - Is nest building an important component of thermoregulatory behaviour in the pouched mouse (Saccostomus campestris)? AB - The thermoregulatory significance of nest building in Saccostomus campestris was investigated by examining the effect of temperature and photoperiod on the size and thermal conductance of nests built within artificial burrows by pouched mice from four localities in southern Africa that experience contrasting thermal conditions. There was no correlation between the amount of nesting material used and the thermal conductance of nests, which indicates that nest size was not a reliable measure of nest quality. For this reason, the significant interactive effect of sex and locality on the quantity of nesting material used, and the significantly larger nests built by wild-caught animals, appear to be unrelated to differences in nesting ability, particularly as there were no similar differences in the thermal conductance of nests between these groups. Several animals blocked the entrance to their artificial burrows and caused a significant reduction in the rate of heat loss from nests therein. However, heat conservation may not have been the primary function of plugging burrow entrances because this did not occur more frequently at lower temperatures and was not more common among animals from cooler localities. Instead, animals that sealed the entrance to their burrows were found to hoard significantly more food than animals that left the entrance open, which suggests that burrows may have been blocked to prevent the potential theft of stored food. Despite substantial variability in both the size and thermal conductance of nests built throughout the present study, there was no significant effect of temperature, photoperiod, or locality on these characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777604 TI - Stimulation of fluid intake by maltodextrins and starch. AB - Maltodextrin solutions are more potent stimulators of fluid intake than are starch suspensions, even though these two substances are both glucose polymers. When rats were offered a choice of two fluids, one containing maltodextrin and the other containing the same concentration of starch, rats preferred maltodextrin; this preference increased over successive days for rats given 7.4% or 10% carbohydrate but not for rats given 1% carbohydrate. Rats offered fluids containing artificial flavors mixed with maltodextrin and starch acquired preferences for flavors paired with 10% or 7.4% maltodextrin but not for flavors paired with 1% maltodextrin. In an attempt to determine whether this greater preference for maltodextrin is due to an innate flavor preference, rats were given a choice of maltodextrin containing sucrose octaacetate vs. plain starch; these rats initially preferred starch but subsequently ingested more maltodextrin flavored with sucrose octaacetate than plain starch. Direct evidence for a postingestive factor was obtained by giving rats intragastric infusions of either maltodextrin, starch, or vehicle whenever they drank a dilute saccharin solution. Both carbohydrates stimulated fluid intake, but maltodextrin did so more rapidly (within 1 day rather than the 2 days of training required with starch infusions). These results indicate that some difference in the postingestive effects of maltodextrin and starch contributes to the greater intake-stimulating effect of maltodextrin. The postingestive factor responsible for the difference between maltodextrin and starch has not been identified, but it is not the amount of utilizable energy because rats prefer maltodextrin over starch even when the starch suspension contains more calories than does the maltodextrin solution. It is proposed that the postingestive factor differentiating these substances is rate of digestion. PMID- 7777606 TI - Effects of illumination and handling upon rat open field activity. AB - Eighty male rats (Crj:CD, 4 weeks old), were randomly assigned to four groups in a 2 x 2 (brightness x handling) factorial design. Ambulation and three types of defecations [pre-open-field defecation (PRD), post-open-field defecation (POD), and testing defecation (TD)] were examined for 3 consecutive days, for 3 min per day. In this study, the effects of handling treatment were illumination dependent. The changes in TD and POD were opposite in relation to the trial day, whereas the changes during the trial, the sum of the TD and POD, were invariable. Considering the invariable changes of the sum of TD and POD, time per trial may be an important factor to measure emotional activity. The TD-POD inversion may reflect the strength of the stress response against a novel placement in open field, because of the change of the time for evoking defecation behavior. PMID- 7777607 TI - Acute intraventricular CRF lowers the hoarding threshold in male rats. AB - The influence of intracerebroventricular rat-CRF on the food-hoarding behavior of rats has been studied in relation to the animals' body weights. A group of six male rats was trained to feed every day from 1000 to 1200 h. Then their threshold for the onset of food hoarding was measured from the intercept of regression line of food hoarded during meal time vs. body weight with the x-axis. Thirty minutes before the hoarding session, the rats received 4 micrograms CRF, or saline control, in the lateral ventricle. The mean threshold for food hoarding was significantly lowered to 299 +/- 61 g after CRF, from control 418 +/- 68 g. Mean food intake during the hoarding sessions was also diminished to 6.0 +/- 0.6 g after CRF, from control 14.5 +/- 0.5 g. These results suggest that the set-point for body weight regulation is acutely lowered by intracerebral CRF. PMID- 7777608 TI - Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat. AB - Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777609 TI - Pancreatic beta-cell function and islet-cell proliferation: effect of hyperinsulinaemia. AB - Pancreatic beta-cell function was studied in adult female rats, in which endogenous insulin demand was fully met by SC infusion of human insulin (4.8 IU/24 h) for 6 days, resulting in hyperinsulinaemia and severe hypoglycaemia. The amount of pancreatic endocrine tissue declined by 40%, (pro)insulin mRNA, as determined by in situ hybridisation by 95%, and the amount of stored insulin by 90%. Islet-cell proliferation as determined by 24 h of BrdU infusion declined by 60%. Basal glucose levels normalized within 2 days after the insulin treatment was ended, whereas about 1 week was needed to restore the amount of pancreatic insulin, glucose-induced insulin release, and glucose tolerance to normal values. The amount of endocrine tissue recovered within 48 h and mRNA abundance within 96 h after discontinuation of the insulin infusion, whereas at that time islet-cell proliferation still showed a sixfold increase, before returning to control levels after 1 week. These results show that after a period of suppression of beta-cell function, recovery of insulin synthetic capacity does not immediately result in normalization of insulin stores and insulin release. Under these conditions, episodes of hyperglycaemia may occur, which may act as a stimulus for islet-cell proliferation. PMID- 7777610 TI - Modification of body temperature and sleep state using behavioral conditioning. AB - Previous research has demonstrated the conditionability of events within the acute-phase response. This study examined whether two such responses, fever and sleep alterations, were conditionable in the rat during the dark photoperiod. The experimental animals were administered a novel saccharin solution as the conditioned stimulus (CS) in conjunction with lipopolysaccharide as the unconditioned stimulus (UCS). This group displayed significantly higher body temperatures than controls upon saccharin representation, 7 days after the original CS-UCS pairing. The experimental animals additionally displayed a conditioned increase in slow wave sleep (SWS); however, the LPS-induced reduction in rapid eye movement (REM) sleep was unable to be reenlisted. Similar to the acute-response, the conditioned alteration in SWS appeared to be due to an increase in episode frequency, rather than duration. These results suggest that the multiple acute-phase events may be simultaneously conditionable, producing an optimum environment for pathogen elimination. PMID- 7777611 TI - Daily cycles in body temperature, metabolic rate, and substrate utilization in pigeons: influence of amount and timing of food consumption. AB - Pigeons lived in individual chambers where instantaneous metabolic rate (MR; indirect calorimetry), body temperature (Tb), and substrate utilization (RQ) were measured 24 times each hour throughout the 12h:12h light:dark cycle. The amount of food consumed influenced the amplitude of the MR and Tb cycles, primarily by affecting the dark-phase segment of the cycle: when food was consumed ad lib, low amplitude daily cycles in MR and Tb occurred in which levels in the dark phase were lower than in the light; during reduced food intake in restricted feeding or in fasting, high-amplitude cycles occurred primarily because nocturnal hypometabolism and hypothermia developed; in restricted feeding, the level of MR and Tb during the dark-phase segment of the cycle was directly related to short term variation in amount consumed. The timing of food consumption primarily affected the light-phase segment of the MR and Tb cycles: when feeding was restricted to a time late in the light phase, these measures became depressed early in the light phase, and then greatly elevated near the scheduled time of feeding. This distinctive light-phase pattern developed quickly after the restricted feeding schedule began and may reflect the influence of a circadian food-entrainable oscillator. RQ indicated carbohydrate utilization for most of the 24-h cycle during ad lib feeding and in restricted feeding. However, approximately 2 h before the first feeding bout of the day, the RQ cycle indicated a sizable shift towards lipid utilization, which terminated after the bout was completed. There was a smaller, more transient, decrease in RQ near the time of the light-dark transition, which may imply cessation of digestive activity in preparation for the nocturnal decrease in Tb. During fasting, RQ indicated lipid utilization throughout the entire cycle. Whole-day energy expenditure by pigeons in these laboratory circumstances was shown to be closely related to the changes in within-day cycles associated with variations in the amount and timing of food intake. PMID- 7777612 TI - Central action of basic fibroblast growth factor on ingestive behaviour in mice. AB - Intracerebroventricular (ICV) infusion of basic fibroblast growth factor (FGF-2) at 50 ng/h for 5 days in male BALB/c mice suppressed the daily intakes of water and food (n = 4). Intakes were reduced on the second day, and were suppressed until the second day after stopping the infusion. The same infusion for 4 days had little effect on the high intakes of 0.3 M NaCl solution and water induced by prolonged ICV infusion of angiotensin II, or the daily food intake in these experiments (n = 7). However, the same infusion for 3-4 days reduced the increased intake of NaCl solution in Na-depleted mice (n = 8), reduced the increased water intake of water-restricted mice (n = 6 or n = 7), and reduced daily food intake in both experiments. Ventricular enlargement was noted in mice at the end of these experiments but, for reasons advanced, did not appear to account for the responses. The results indicate that FGF-2 may have an inhibitory role in these ingestive behaviours. PMID- 7777613 TI - Preference for NaCl solutions in sham drinking Sprague-Dawley rats: water deprivation, sodium depletion, and angiotensin II. AB - Male Sprague-Dawley rats were fitted with closable gastric fistulas and were then tested under closed fistula (real intake) and open fistula (sham intake--fluids drain from the stomach without appreciable absorption) conditions in one of three states: fluid deprivation, sodium depletion, and infusion of angiotensin (Ang) II. Water and various concentrations of NaCl were offered to drink in 1-h one- or two-bottle intake tests. In Experiment 1, water-deprived rats with closed fistulas drank more 0.15 M NaCl than either water or 0.3 M NaCl, offered in one bottle tests. In sham drinking tests, the intake decreased monotonically as NaCl concentration increased. In two-bottle tests, water was greatly preferred over NaCl solutions. In Experiment 2, sodium-depleted rats preferred NaCl over water, again demonstrating a peak intake at 0.15 M in closed fistula conditions. However, with the fistula open the intakes of 0.05 and 0.15 M were similar, and 0.45 M considerably lower. In Experiment 3, Ang II-infused rats consumed both water and NaCl in two-bottle tests in both open and closed fistula trials. The quantity ingested on sham trials was only modestly elevated over real intake trials with Ang II compared with sham tests in Experiments 1 and 2. PMID- 7777614 TI - Glucose homeostasis and sympathoadrenal activity in mercaptoacetate-treated rats. AB - The effect of the fatty acid oxidation inhibitor, sodium mercaptoacetate (MA, 600 mumol/kg) on peripheral energy substrate metabolism was investigated in rats with permanent heart catheters. Rats were either fed, 48-h food deprived, or exercising for 30 min. Before and after intravenous MA injection, stress-free blood samples were taken for measurement of blood glucose, plasma free fatty acids (FFA), insulin, epinephrine (E), and norepinephrine (NE) concentrations. In fed animals, MA increased blood glucose, plasma FFA, and NE and decreased insulin concentrations. Plasma E levels did not change. In 48-h-deprived animals, MA elevated low baseline glucose concentrations to levels observed in MA-treated fed animals. Plasma insulin concentrations decreased to almost undetectable levels. Plasma catecholamines and FFA were increased compared to fed rats. In exercising rats, MA caused an exaggerated increase of blood glucose and a pronounced reduction of plasma insulin without affecting exercise-induced FFA and catecholamine responses. The data revealed that the mechanisms that regulate blood glucose concentrations during MA treatment are dependent on the nutritional state and ambient energy expenditure. PMID- 7777615 TI - An evaluation of the use of total body electrical conductivity for the estimation of body composition in adult rats: effect of dietary obesity and adrenalectomy. AB - Total body electrical conductance (TOBEC) has been recommended for serial measurements of body composition in animals and humans. This study examined the accuracy of the TOBEC technique in predicting body composition of a population of adult male rats that had undergone seven different treatments, including adrenalectomy and blocking of glucocorticoid receptors, in the study of the etiology of obesity. The predicted body composition values of the animals (n = 57, body weight 550 +/- 8 g) obtained by using the manufacturer's and Baer's equations were compared to the actual body composition obtained by direct carcass analysis. Both equations underestimated lean body mass and reciprocally overestimated body fat (manufacturer's 103 +/- 4 g, Baer's 55 +/- 3 g). A new prediction equation was developed based on the conductivity index and the actual lean body mass. This revised equation was able to accurately estimate the lean body mass of the animals used in the same experiment but over-estimated lean body mass of larger animals (n = 10, wt. 647 +/- 13 g). Conclusions based on multiple comparisons (Duncan's) of predicted and actual values resulted in different effects of treatments on body composition. To improve accuracy and reliability of the TOBEC technique, a prediction equation should be developed from the same population as the studied population, and experimental group sizes used for examining treatment effects should be relatively large. PMID- 7777616 TI - Amiloride suppression of the taste intensity of sodium chloride: evidence from direct magnitude scaling. AB - The transduction of Na+ salts has been shown in many species to be mediated in part by an epithelial ion channel on the apical surface of the taste receptor cell membrane, which is blockable by the diuretic amiloride. In addition to this apical ion channel, Na+ is also transduced via a paracellular pathway, which is not sensitive to amiloride. There are significant species differences in the contribution of the amiloride-sensitive pathway to Na+ transduction. Previous human psychophysical studies have reported conflicting results on the effects of amiloride in suppressing the intensity of NaCl. In general, these studies used amiloride doses that were much higher than those showing clear suppressive effects in electrophysiological studies in other species. In the present experiment, we used direct magnitude scaling of the intensities of five NaCl concentrations flowed over the anterior portion of the tongue to determine the effects of amiloride treatment at lower doses. NaCl was presented after adaptation of the tongue to water or mixed with and presented after adaptation to 10, 50, or 100 microM amiloride-HCl. Subjects estimated the intensity of NaCl and of these concentrations of amiloride in each treatment condition using magnitude estimation with a 0.1 M NaCl modulus presented following a water rinse prior to each session. Results showed that amiloride had a significant suppressive effect on the perceived intensity of NaCl, with a similar effect seen at all three amiloride doses. The psychophysical function after amiloride showed a parallel shift to the right. The average suppression over all NaCl concentrations was 21%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777617 TI - A reevaluation of dimethyl disulfide as a sex attractant in golden hamsters. AB - Dimethyl disulfide (DMDS) is present in hamster vaginal secretion and has been reported to be responsible for a sizable proportion of a male hamster's attraction to vaginal secretion. We evaluated this claim by testing two predictions that follow from its purported pheromonal role: (a) male hamsters should spend more time than females investigating DMDS; and (b) attraction to DMDS by males should be dependent on testosterone. In the first experiment, males investigated vaginal secretions more than females, but no sex difference was apparent in investigation of DMDS or a control odor. In the second experiment, gonadectomized males with testosterone implants investigated vaginal secretion more than castrates without testosterone; however, these hormone manipulations did not affect the attraction of males to DMDS or the control odor. We conclude that DMDS does not elicit sex differences in attraction and that in males the attraction to DMDS is not dependent on gonadal hormones. These results suggest that DMDS is not a sex attractant by itself nor is it a major component of an attractant mixture. PMID- 7777618 TI - Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory. AB - The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777619 TI - Saccharin-induced increase in daily fluid intake as a predictor of voluntary alcohol intake in alcohol-preferring rats. AB - This study examined the relationship between saccharin intake and ethanol consumption in alcohol preferring (P) rats and Fawn Hooded (FH) rats before and after exposure to forced ethanol (10%, v/v) solution. Both groups exhibited large increases (> 2X) in daily fluid intake (DFI) when saccharin (0.1%, w/v) was present and exhibited moderate levels of ethanol intake. Only the P rats significantly increased their ethanol consumption after exposure to ethanol as the sole drinking fluid. Correlational analyses revealed that the absolute intakes of saccharin and ethanol were not significantly correlated in either group, but the increase in DFI in the presence of saccharin was highly correlated with ethanol intake after forced ethanol exposure (r > +0.8; p < 0.05). Similarly, when correlations were conducted for these variables over both the P and FH groups, the correlation between increase in DFI in the presence of saccharin and alcohol intake was significantly higher than that between saccharin and alcohol intakes. Reexamination of previous data from 6 different rat strains also revealed a significant correlation between increase in DFI in the presence of saccharin and ethanol intake. These findings suggest that the dramatic increase in of DFI in the presence of saccharin may be an animal analog of the clinical phenomenon known as a loss of control. PMID- 7777620 TI - Effect of inhibition of gluconeogenesis on arginine-induced insulin secretion. AB - It is well known that several amino acids, such as arginine, are potent stimuli for insulin and glucagon secretion from the pancreas. Recently, vagal arginine sensors, which modulate arginine-induced pancreatic hormone secretion, have been reported to exist in the liver. The present investigation was designed to evaluate the role played by gluconeogenesis in this hepatic influence. To this end, we studied the effects of an intraperitoneal injection of 3 mercaptopicolinic acid (3-MPA), a gluconeogenic inhibitor, on the pancreatic hormonal response induced by intraperitoneal administration of arginine (1 g/kg body mass) to hepatic vagotomized and sham vagotomized rats. Fifteen min following the injection of arginine, the increases in glucose and insulin concentrations were significantly lower in rats with an inhibited gluconeogenesis than in rats with an intact capacity for gluconeogenesis. There were no effects of the hepatic vagotomy on the arginine-induced hormonal responses either with or without the 3-MPA injection. The results suggest that gluconeogenesis is implicated in the hepatic modulation of arginine-induced pancreatic hormone secretion. PMID- 7777621 TI - Active immunization against insulin affects sleep and feeding in rats. AB - The effects of active immunization against peripheral insulin on different sleep parameters and food consumption were studied in rats. Insulin coupled to thyroglobulin was used as immunogen and rats immunized with thyroglobulin alone served as controls. Active immunization against insulin is summarized as follows: (a) the number of arousals was reduced; (b) waking time decreased by about 20%; (c) slow wave sleep was increased; (d) The amount of sleep increased during the light and dark period; (e) feeding was decreased; (f) body weight was reduced; and (g) the blood glucose level rised. These results are compatible with previous studies showing positive correlation between decrease of insulin secretion, sleep disturbances and decrease of feeding. A possible association between peripheral insulin and brain noradrenergic system, sleep and feeding is suggested. PMID- 7777622 TI - Repeated blood glucose measures using a novel portable glucose meter. AB - We describe the use of a novel portable blood glucose meter to repetitively and rapidly measure blood glucose levels in mice. We used this apparatus to replicate in the mouse, an insulin tolerance test (ITT) developed for humans. This test involves repeated glucose sampling (0, 1, 3, 5, 7, 10, 15, and 20 min) after an IV bolus of 0.4 IU/Kg of insulin. We first ran comparative tests with a conventional automated glucose analyser to assess the precision and reliability of the blood glucose meter for use in the mouse. High correlation were found between the two measures using either capillary or trunk whole blood. The variability of measurement over five consecutive determinations was about 3%. It was possible to take repetitive measures at about 70 s intervals. PMID- 7777623 TI - Surgical reconstruction of patients with Crouzon's syndrome: a lifetime of needs. AB - Crouzon's Syndrome is an inherited craniofacial deformity. Unfortunately, like with many other complex disorders, there is no quick fix. Treatment consists of numerous surgeries over a long period of time. Nurses are crucial team members as they are best educated to balance the physical, psychosocial, and developmental needs of patients and families. PMID- 7777624 TI - Malignant hyperthermia: a review. AB - Malignant hyperthermia (MH) was first identified as an anesthetic-related patient syndrome with familial tendencies in 1960. It is defined as a chain reaction of abnormalities triggered in susceptible individuals by commonly used anesthetic agents, and is classified as a hypermetabolic disorder of skeletal muscle. It is believed that susceptible patients possess a genetic predisposition for the development of the disease. In an acute episode of MH, the anesthetic triggering agent appears to interfere with the calcium ion reentry into the sarcoplasmic reticulum after muscle contraction. This process involving the calcium ion is the basis for all the clinical symptoms observed. PMID- 7777625 TI - Is it quality assurance or quality improvement; and what is it? AB - The term quality has a different meaning for everyone. Persons seeking health care have predetermined expectations that the care they receive is efficient, effective, and meets their needs. Through nursing quality improvement programs, nurses themselves can evaluate the efficiency of the care they provide. Through the use of patient surveys, nurses become aware of the patient's needs and degree of satisfaction. Monitor tools based on nursing standards and policies are used to assess the components of care. A successful nursing quality improvement program requires a climate that educates, supports, and encourages staff involvement. PMID- 7777626 TI - Paradigms for successful management in 1995. PMID- 7777627 TI - Patient education materials for facelifts and blepharoplasty. PMID- 7777628 TI - Guidelines for surgical decontamination. PMID- 7777629 TI - Interpretation: what do the study results mean? PMID- 7777630 TI - Ethical codes and policy standards affecting health care practice and research: a bibliography. PMID- 7777631 TI - Arteriovenous malformations: a team approach to management. PMID- 7777633 TI - President's message: promoting excellence in nursing care begins with students! PMID- 7777632 TI - Heck, it could be worse. PMID- 7777634 TI - Common injuries in the child or adolescent athlete. AB - As more primary care physicians enter the field of Sports Medicine, they will inevitably encounter more injured young athletes than what they may have experienced in their private practices. Recognizing the differences that exist between the young athlete and adult is essential in properly diagnosing and rehabilitating these athletes. As mentioned in our previous article (Caring for the School-Aged Athlete, Primary Care, December 1994), comprehensive care of the young athlete can be quite involved and somewhat different from care of the adult population. This article focuses on some specific injuries unique to younger, skeletally immature athletes, while mentioning the differential diagnosis of some of the other common sports injuries shared by both younger and older athletes. PMID- 7777635 TI - Contraception in the adolescent patient. AB - Having presented an overview of the available methods of contraception, the authors present one approach to prescribing contraceptives based on their experience. First, adolescent patients in our practice are discouraged from engaging in sexual intercourse. Abstinence is the only fail-safe method of contraception and provides benefits both emotionally and physically (i.e., prevention from sexually transmitted diseases and unwanted pregnancies). If the adolescent plans to be sexually active, however, she is encouraged to select some form of hormonal contraception, namely Norplant, Depo-Provera, or oral contraceptives, in conjunction with condoms. The authors have had little success recommending barrier methods alone. Condoms are used sporadically and the diaphragm is very awkward for adolescents who are still uncomfortable with their bodies and with touching themselves. Of the three hormonal methods, Depo-Provera seems to be well-accepted by our patients. It offers several advantages that we believe make it attractive. First, it does not require any forethought by the patient other than coming in for the injection every 3 months. There is an effective grace period, so the patient is afforded good contraception even if she is up to a month late for her injection. The frequent visits for injections actually can be looked upon as positive, frequent contacts with the patient and can provide opportunities for counseling. In addition, some patients become amenorrheic, which teens view as an advantage, increasing compliance. If it is not likely that a patient will be compliant with every-3-month injections, Norplant is recommended. Studies have shown good acceptance of Norplant by adolescents and that has been the experience of the authors. With appropriate counseling prior to insertion and a counseling session with patients who request removal, the number of actual Norplant removals has been limited. If Depo-Provera and Norplant are not acceptable to the patient, then oral contraceptives are recommended. Of the three methods, more opportunities for failure exist with oral contraceptives. Pills are missed for a variety of reasons, including going away for the weekend; not having a regular schedule, which can interrupt pill-taking; and even ambivalence about becoming pregnant. One recent study demonstrated certain patient characteristics that were associated with good compliance with oral contraceptives, including white race, higher education level, suburban residence, and older age of both the patient and her mate. Keeping these characteristics in mind may be helpful when prescribing oral contraceptives. Of course, it is the patient's prerogative to choose the type of contraception she feels will be best suited for her.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777636 TI - Managing the child infected with HIV. AB - Care of the HIV-infected/exposed infant and child is both routine and challenging. Routine well child care and immunizations are an important part of maintaining and monitoring health status. Challenges arise in the management of acute illnesses and the numerous crises that are experienced by the family caring for that child. Therapy guidelines now provide a logical way in which to initiate antiretroviral treatment and PCP prophylaxis. In HIV-infected children with early disease, common pathogens initially predominate, and only in advanced immune suppression does care become complicated enough to require expert consultation. With increasing numbers of HIV-infected women, perinatally acquired infections in infants will become more common. Early testing and identification will increasingly be important as a way to impact on the significant morbidity and mortality seen in infants less than 6 months old. A caring, compassionate, and comprehensive approach to the care of HIV-infected infants and children results in increased survival and lengthening of disease-free time. Providing this vitally needed care is both satisfying and stimulating. PMID- 7777637 TI - Assisting with school placement and intervention for children with special needs- from disabled to gifted. AB - Collaboration of physicians, parents, and teachers is essential in obtaining the best education for children. The spectrum of interaction ranges from acute and chronic medical care, routine exams, and sports evaluations to learning disabilities and attention-deficit hyperactivity disorder to giftedness. PMID- 7777638 TI - Children and environmental toxins. AB - Environmental toxins have been shown to produce harmful effects in children, who may be exposed in the home, in public spaces, and by passive contact with adults. This review discusses common toxic substances, including lead, radon, tobacco smoke, asbestos, pesticides, mercury, carbon monoxide, and electric/magnetic fields. The focus is on identification, environmental abatement, and parent education. Practical suggestions for the primary care clinician in a community setting are emphasized. PMID- 7777639 TI - Common behavioral problems in infants and children. AB - Primary care physicians can serve as important sources of behavioral information to patients of infants, toddlers, school-aged children, and adolescents. Behavior results from a blend of biologic qualities, such as gender and temperament, and social experiences, such as attachment and family experiences. Common problems include disorders of sleep, crying, feeding and diet, discipline and sexuality, aggression and biting, toilet training, and school avoidance. Family physicians should be aware of the management of behavioral problems and provide anticipatory or responsive guidance or reference information. PMID- 7777640 TI - Common skin problems of infancy, childhood, and adolescence. AB - Common dermatological problems as a frequent presenting complaint are stratified by infancy, childhood, and adolescence. The common manifestations and questions asked by parents are discussed. Both infectious and noninfectious rashes are included. Convenient treatment modalities are listed. PMID- 7777641 TI - [Changes in biological rhythm and sleep structure during the menstrual cycle in healthy women]. AB - It is well known that clinical symptoms such as psychosis, epileptic seizures and sleep disturbances aggravate around the time of menstruation. In some healthy women, subjective sleep feelings or moods have been reported to change throughout the menstrual cycle, which suggests that sleep structure and sleep-wake rhythm may change during the menstrual cycle. We investigated a circadian pattern of plasma melatonin, sleep-wake rhythm and sleep characteristics in the different phases of the menstrual cycle in young healthy women under controlled environmental conditions. The subjects were seven healthy women, aged 18 to 19, with regular menstrual cycles. They stayed in an experimental facility, where temperature and humidity were kept within a narrow range, for three days in successive five weeks. They got up and went to bed at their preferable time. Polysomnography was performed using ambulatory cassette EEG system on the first and second night. Sleep stages were scored according to Rechtshaffen and Kales' criteria. Plasma melatonin was measured at 1-hour intervals for 24 hours on the third day. The menstrual cycle was divided into four phases (menstruation, follicular, early luteal and late luteal). Although the plasma melatonin level in the late luteal phase tended to be higher than in other phases, no significant difference was observed across four phases. The phase in plasma melatonin level did not change. As for sleep-wake rhythm, the time of getting up on the first day was significantly late in the late luteal phase (p < 0.05), although it showed no significant change on the second day. The time of going to bed did not change. Sleep characteristics changed during the menstrual cycle. There was a significant difference in the amount of stage 3 + 4, slow wave sleep (p < 0.05), which was more abundant in the follicular phase than in the luteal phase. TIB (time in bed), SPT (sleep period time), TST (total sleep time) seemed to increase in the menstrual and follicular phases, while stage W increased in the early and late luteal phases. However, there were no significant differences in these parameters. The other parameters did not show any changes. The changes in amount of stage 3 + 4 throughout the menstrual cycle seem to be due to endogenous factors, because environmental factors were controlled in this experiment. It is possible that the menstrual cycle also affect the plasma melatonin level and sleep-wake rhythm. PMID- 7777642 TI - [Case report of a schizophrenic patient who exhibited amnesia of personal history for 15 years]. PMID- 7777643 TI - [Care for patients with Pick's disease--by using their preserved procedural memory]. AB - Pick's disease are more often complicated than Alzheimer's disease by behavioral disturbances such as social misconduct and stereotypy, that are troublesome and clinically difficult to manage. The purpose of this study was to investigate the possibility of improvement in care for patients with Pick's disease by using their presumably preserved procedural memory. Four inpatients and two outpatients with Pick's disease were studied. Case 1: A 54-year-old right-handed retired clerk presented with a 3-year history of increasing restlessness, word-finding difficulty and impaired comprehension of nominal terms. He was forced to retire from his work because of his social misconduct and incommunicability. On admission he wandered about the ward irritably, did not enter into any conversation, and destroyed all keys in the ward by putting a pencil into keyholes. Neuroradiological examination revealed circumscribed bilateral frontotemporal atrophy which was more marked on the left side. However, he has become more adaptive to the life in the ward and his expression has become peaceful since he began to play othello games with other patients and his doctors. Case 2: A 71-year-old right-handed housewife had progressively altered in her personality and behavior over 4 years. She was restless and showed striking palilalia with marked right frontotemporal atrophy when initially evaluated 2 years after her initial symptoms. Subsequently, her verbal output decreased. She ate large amounts of food and her overweight became a serious problem in her care at home. On admission she wandered about the ward irritably, ate meals of other patients, and put on a quilt on their head. However, these troublesome behavior disappeared when she was bent on knitting that was her former hobby. Case 3: A 63-year-old right handed physician presented with a 5 year history of increasing word-finding difficulty and impaired comprehension of nominal terms. His conversation was limited to continuous repetition of a few phrases. He wandered into several hospitals around his house in fixed order every day. On examination, he was mildly disinhibited and distractible with circumscribed bilateral frontotemporal atrophy which was more marked on the left side. Wandering away from home overnight necessitated admission to the hospital. In the ward he wandered about and tried to open each door restlessly and irritably. However, he has become calm and his expression has become peaceful since he was conducted to measure blood pressures of his nurses. Case 4: A 65 year-old right-handed retired office worker.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777644 TI - Assessment of the Rescorla-Wagner model. AB - The Rescorla-Wagner model has been the most influential theory of associative learning to emerge from the study of animal behavior over the last 25 years. Recently, equivalence to this model has become a benchmark in assessing connectionist models, with such equivalence often achieved by incorporating the Widrow-Hoff delta rule. This article presents the Rescorla-Wagner model's basic assumptions, reviews some of the model's predictive successes and failures, relates the failures to the model's assumptions, and discusses the model's heuristic value. It is concluded that the model has had a positive influence on the study of simple associative learning by stimulating research and contributing to new model development. However, this benefit should neither lead to the model being regarded as inherently "correct" nor imply that its predictions can be profitably used to assess other models. PMID- 7777645 TI - Adult attachment representations, parental responsiveness, and infant attachment: a meta-analysis on the predictive validity of the Adult Attachment Interview. AB - About a decade ago, the Adult Attachment Interview (AAI; C. George, N. Kaplan, & M. Main, 1985) was developed to explore parents' mental representations of attachment as manifested in language during discourse of childhood experiences. The AAI was intended to predict the quality of the infant-parent attachment relationship, as observed in the Ainsworth Strange Situation, and to predict parents' responsiveness to their infants' attachment signals. The current meta analysis examined the available evidence with respect to these predictive validity issues. In regard to the 1st issue, the 18 available samples (N = 854) showed a combined effect size of 1.06 in the expected direction for the secure vs. insecure split. For a portion of the studies, the percentage of correspondence between parents' mental representation of attachment and infants' attachment security could be computed (the resulting percentage was 75%; kappa = .49, n = 661). Concerning the 2nd issue, the 10 samples (N = 389) that were retrieved showed a combined effect size of .72 in the expected direction. According to conventional criteria, the effect sizes are large. It was concluded that although the predictive validity of the AAI is a replicated fact, there is only partial knowledge of how attachment representations are transmitted (the transmission gap). PMID- 7777647 TI - Vocational rehabilitation of drug abusers. AB - Employment has been identified as an important element in the rehabilitation of drug abusers and, together with abstinence from illicit drugs and criminal involvement, is frequently used as a criterion of treatment outcome. The research literature for the last 20 years on variables affecting employment and the vocational rehabilitation of drug abusers is reviewed with an emphasis on (a) the identification of variables influencing the employment of drug abusers and (b) the evaluation results of interventions that have been developed for this purpose. It is concluded that a number of programs have been demonstrated to have had some success in the vocational rehabilitation of drug abusers. Specific recommendations are made concerning both the direction of further research in this area and the application of existing knowledge in current practice. PMID- 7777646 TI - Of the way we were: adult memories about attachment experiences and their role in determining infant-parent relationships: a commentary on van IJzendoorn (1995). AB - In his meta-analysis of studies demonstrating the predictive validity of the Adult Attachment Interview (AAI), van IJzendoorn (1995) relies on current thinking in attachment theory. Although the data he presents are forceful, there are alternate explanations for the relations he finds that are ignored. Narrative about personal memories may be a function of personal theories about developmental processes as well as current psychological state (e.g., personal self-esteem). There is currently no evidence that the coherency of discourse about early childhood experiences is a function of either actual early experience or reworkings of that experience. In the absence of such evidence, the data indicating that maternal personality influences infant behavior are not theoretically surprising. PMID- 7777648 TI - Life events and bipolar disorder: implications from biological theories. AB - Although a number of studies suggest that stressful life events play a role in bipolar disorder, methodological flaws impose serious limitations on this literature. Nonetheless, better designed studies indicate that life events influence the course of bipolar disorder. Little is known, however, about the nature of events that are of particular importance to this disorder. Given the strong biological vulnerability and the unique clinical aspects of bipolar disorder, certain forms of stress may have stronger interactions with vulnerability characteristics. Three major biological theories of bipolar disorder are discussed, with particular attention to their implications for investigations of life events. Although tenuous, these models suggest that greater attention needs to be paid to particular dimensions of life events and the course of disorder. PMID- 7777649 TI - Effects of psychotherapy with children and adolescents revisited: a meta-analysis of treatment outcome studies. AB - A meta-analysis of child and adolescent psychotherapy outcome research tested previous findings using a new sample of 150 outcome studies and weighted least squares methods. The overall mean effect of therapy was positive and highly significant. Effects were more positive for behavioral than for nonbehavioral treatments, and samples of adolescent girls showed better outcomes than other Age x Gender groups. Paraprofessionals produced larger overall treatment effects than professional therapists or students, but professionals produced larger effects than paraprofessionals in treating overcontrolled problems (e.g., anxiety and depression). Results supported the specificity of treatment effects: Outcomes were stronger for the particular problems targeted in treatment than for problems not targeted. The findings shed new light on previous results and raise significant issues for future study. PMID- 7777650 TI - Sexual fantasy. AB - This article reviews the research literature on sexual fantasy, a central aspect of human sexual behavior. Topics include (a) gender similarities and differences in the incidence, frequency, and content of sexual fantasies and how they relate to sociocultural and sociobiological theories of sexual behavior; (b) the association between frequency or content of sexual fantasies and variables such as age, sexual adjustment and satisfaction, guilt, sexual orientation, personality, and sexual experience; and (c) "deviant" sexual fantasies (i.e., what they are, whether they play a role in the commission of sexual crimes, and whether they can be modified). The article ends with a summary of major findings and suggestions for future research. PMID- 7777651 TI - The need to belong: desire for interpersonal attachments as a fundamental human motivation. AB - A hypothesized need to form and maintain strong, stable interpersonal relationships is evaluated in light of the empirical literature. The need is for frequent, nonaversive interactions within an ongoing relational bond. Consistent with the belongingness hypothesis, people form social attachments readily under most conditions and resist the dissolution of existing bonds. Belongingness appears to have multiple and strong effects on emotional patterns and on cognitive processes. Lack of attachments is linked to a variety of ill effects on health, adjustment, and well-being. Other evidence, such as that concerning satiation, substitution, and behavioral consequences, is likewise consistent with the hypothesized motivation. Several seeming counterexamples turned out not to disconfirm the hypothesis. Existing evidence supports the hypothesis that the need to belong is a powerful, fundamental, and extremely pervasive motivation. PMID- 7777652 TI - Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion. AB - Besides sleep-promoting properties, delta-sleep-inducing peptide (DSIP) has been reported to act as a corticotropin-releasing inhibiting factor in vitro and in vivo. We examined, first, the influence of DSIP on ACTH and cortisol release following stimulation with human corticotropin-releasing hormone (h-CRH; 1.0 microgram/kg body weight, and 0.5 microgram/kg body weight, respectively) in healthy young men (n = 5 in each condition). DSIP (total doses of 3 and 4 mg, respectively, vs. placebo) was infused intravenously between 30 min prior to and 90 min after CRH injections. Responses of ACTH and cortisol were almost identical during and after infusion of DSIP and placebo. In a second experiment, the influence of DSIP (4 mg, also administered as intravenous infusion) on meal related ACTH and cortisol secretion was studied in another 10 men. Meal-related midday surge of ACTH and cortisol was also not affected by DSIP. Our data do not support an inhibitory role of DSIP on ACTH and cortisol secretion in man. PMID- 7777653 TI - Differential inhibition of stress-induced adrenocortical responses by 5-HT1A agonists and by 5-HT2 and 5-HT3 antagonists. AB - The present studies were designed to determine the effects of 5-HT1A receptor agonists and 5-HT2A/2C and 5-HT3 antagonists on adrenocortical responses to a variety of stress paradigms in conscious male rats. The following stressors were examined: acoustic stress (105 dB for 2 min); foot shock (0.2 mA, five shocks over 5 min); conditioned fear (animals placed in the foot shock chamber for 5 min, 24 h after foot shock); restraint (Plexiglas restrainer for 5 min); injection of recombinant human interleukin-1 alpha (IL-1, 20 micrograms/kg, IP); injection of cocaine hydrochloride (20 mg/kg, IP). Drug treatments consisted of intracerebroventricular (ICV) or intraperitoneal (IP) injections of the 5-HT1A agonists, 8-OH-DPAT and ipsapirone (0.1 pmol, ICV), the 5-HT2A/2C antagonist, ketanserin (2 mumol/kg, IP), and the 5-HT3 antagonist, MDL-72222 (20 nmol, ICV). The plasma corticosterone (CS) responses to foot shock and restraint stress were not affected by any of the serotonergic drugs tested. The 5-HT1A agonist, 8-OH DPAT, was able to attenuate the adrenocortical responses to acoustic stimulation, conditioned fear, IL-1 alpha, and cocaine administration, with ipsapirone also being effective in reducing the responses to acoustic stimulation and cocaine injection. The 5-HT2 antagonist, ketanserin was able to reduce the adrenocortical response in the conditioned fear paradigm and the response to IL-1 alpha injection. The 5-HT3 antagonist, MDL-72222 was only effective in reducing the response to acoustic stimulation. Thus, adrenocortical responses to each of the applied stressors were differentially affected by the 5-HT receptor ligands tested. The results of this study indicate that 5-HT1A agonists may be efficient stress response-reducing agents. However, their efficacy depends on the lack of a somatosensory component to the applied stressor and their agonist properties suggest that their action may not involve direct effects on serotonergic pathways mediating the observed responses. In contrast, the specificity of the 5-HT2 and 5 HT3 antagonists in blocking adrenocortical responses to certain stressors suggests that these drugs exert their effects by blocking serotonergic neurotransmission in pathways mediating the adrenocortical responses to specific stimuli. PMID- 7777654 TI - Daily plasma estradiol and progesterone levels over the menstrual cycle and their relation to premenstrual symptoms. AB - The present study extends a previous report of lower plasma ACTH levels in women with premenstrual syndrome (PMS) compared with asymptomatic controls. Plasma levels of estradiol and progesterone were measured daily in 10 women with confirmed PMS and 8 asymptomatic women. Daily symptom reports were maintained during the same menstrual cycle. Both estradiol and progesterone levels were consistently, but not significantly, higher throughout the cycle in PMS subjects compared with controls. From the follicular to the early luteal phase, estradiol levels were significantly higher in a previously defined PMS subgroup 2 with more severe symptoms throughout the cycle compared with both the less severe PMS subgroup 1 and controls. Progesterone levels were significantly and positively correlated with PMS symptoms along the entire menstrual cycle, preceding the symptoms by 5-7 days. These preliminary results provide support for the hypothesis that the presence of progesterone at early luteal phase levels is required for PMS symptoms to occur. PMID- 7777655 TI - The glucocorticoid sensitivity of lymphocytes changes according to the activity of the hypothalamic-pituitary-adrenocortical system. AB - Cortisol inhibition of phytohemagglutinin (PHA)-induced lymphocyte activation was studied in vitro in peripheral blood mononuclear cells (PBMC) of patients with pathologies of the hypothalamic-pituitary-adrenocortical (HPA) system (n = 18) as well as in students under and out of academic stress. In patients with HPA pathologies, cortisol-induced inhibition of lymphocyte interleukin-2 (IL-2) secretion in vitro positively correlated (p < .005) with IL-2 synthesis, such that lymphocytes secreting less IL-2 were less cortisol sensitive. Similarly, in stressed students there was a positive correlation (p < .02) between lymphocyte DNA synthesis and cortisol inhibition in vitro. Academic stress also resulted in a decrease (p < .01) of lymphocyte cortisol sensitivity. The same tendency was observed in patients with Cushing's syndrome when compared with hypocortisolemic patients. Normal controls whose lymphocytes were glucocorticoid resistant showed higher lymphocyte activation than glucocorticoid sensitive subjects. This pattern of glucocorticoid sensitivity was reversed in individuals with abnormal glucocorticoid secretion due to HPA pathology or stress. PMID- 7777656 TI - Natural killer cell activity is reduced in association with oral contraceptive use. AB - Oral contraceptive (OC) use has been associated with increased incidence of a number of infections, but the mechanisms behind these changes is unclear. The present study compared OC users and nonusers in natural killer (NK) cell activity, NK phenotype, and illness frequency. Subjects were 55 female medical students (19 OC users, 36 nonusers). Three blood samples were obtained, 1 mo apart. Natural cytotoxicity was tested with a 51Cr assay. Self reports of illness symptoms during the previous week were collected at each blood sampling. NK phenotype number was assessed by flow cytometry. Oral contraceptive users had lower natural cytotoxicity and increased frequency of sneezing, gastrointestinal distress, runny nose, sore throat, coughing, and total illness symptoms, relative to nonusers. No differences were found between OC users and nonusers in NK phenotype number. These findings support the hypothesis that differences between users and nonusers in infection rates might be due to alterations in NK activity. PMID- 7777657 TI - Menstrual cycle and social behavior in vervet monkeys. AB - We assessed the relationship between social behavior and the menstrual cycle in 11 adult female vervet monkeys (Cercopithecus aethiops sabaeus) living in an established, stable social group. The findings indicated that fluctuations in ovarian steroids are accompanied by behavioral changes in vervet monkeys. A significant increase in aggressive action, avoidance of social overtures, and retreats from threat occurred during the late luteal phase. However, the social environment can greatly affect behavior independent of the phase of the menstrual cycle. The 10 nondominant (or subordinate) individuals not only exhibited behavioral changes across their own menstrual cycles, but also were responsive to the dominant female's cycle. During the dominant female's late luteal phase, subordinate females significantly increased aggression and decreased social activity. Some of behavioral patterns in female vervet monkeys are therefore relatively independent of direct hormonal modulation and support the contention of the dominant female as the driving force for behavioral changes related to aggression and social interaction. The differential effect of hormones and social status and other environmental factors on behavior has not been critically evaluated in human studies of the premenstrual syndrome. The present study suggests that it is important to assess which behavioral patterns in women are hormonally mediated and which are dependent on the environment. PMID- 7777658 TI - Postweaning housing conditions and partner preference and sexual behavior of neonatally ATD-treated male rats. AB - Male rats were neonatally treated with cholesterol or a substance that blocks the aromatization of testosterone to estradiol (1,4,6-androstatriene-3,17-dione: ATD). At weaning (21 days) they were either housed alone or in small groups (2-3 animals) and tested for partner preference behavior (PPB) in adulthood. Choice was between an estrous female and an active male (Part I) and between an estrous female and an ATD-male (Part II). Tests were carried out in a 3-compartment box. Social isolation did not have major effects on PPB except when sexual interaction with the stimulus animals was prevented (Part I). In this case, isolates (ATD and control) showed higher preference scores (PS) for the estrous female and spent less time in the empty middle compartment. When the choice was between an estrous female and an ATD-male, partner PS decreased in all males, most clearly in ATD males. The latter animals spent more time with the stimulus ATD-male than they had done in previous PPB tests with the normal stimulus male. In contrast to partner preference behaviors, sexual behavior was clearly affected by social isolation. Isolates (ATD and control) displayed lower frequencies of mounts and intromissions. These effects persisted over consecutive tests. Ejaculation was not affected. In conclusion, the present results confirm earlier findings about the significance of neonatal endocrine conditions for the organization of adult PPB in male rats. The presence or absence of social conspecifics after weaning appears to have little influence on adult PPB. PMID- 7777662 TI - Regional differences in fat cell lipolytic mechanisms: a critical review. PMID- 7777659 TI - Gonadotropin (LH and FSH) response after submaximal GnRH stimulation in depressed premenopausal women and healthy controls. AB - Although hormonal response abnormalities in depression have been demonstrated in several hypothalamic-pituitary-target organ axes after a variety of neuroendocrine challenge tests, studies of hypothalamic-pituitary-gonadal (HPG) axis function have been inconsistent in their findings. The use of maximal or supramaximal doses of gonadotropin-releasing hormone (GnRH) in early studies (150 600 micrograms) may have masked the presence of more subtle disturbances in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsiveness in depression. We hypothesized that submaximal doses of GnRH might reveal a more subtle dysregulation in gonadotropin responsiveness in depression, and therefore measured LH and FSH responses after GnRH 10 micrograms and 90 micrograms doses in nine premenopausal depressed women and six healthy controls. There were no statistically significant differences between subject groups for mean basal LH, FSH, and estradiol concentrations, nor for any of the LH and FSH response values after either GnRH stimulation dose. The present observations of an intact HPG axis in depression contrast with findings of disturbances in most other hypothalamic-pituitary axes, and suggest that neuroendocrine dysregulation in depression might not represent a generalized limbic system-hypothalamic-pituitary abnormality, but rather a more restricted lesion sparing the medial preoptic and/or arcuate region of the hypothalamus which regulates gonadotropin secretion. PMID- 7777660 TI - Stress, serotonergic function, and mood in users of oral contraceptives. AB - The relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other large neutral amino acids (LNAAs), mood, and food intake was investigated in women taking monophasic oral contraceptives containing progestagens. Subjects experiencing high levels of stress displayed significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during the pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives. PMID- 7777661 TI - Circadian variations in antigen-specific proliferation of human T lymphocytes and correlation to cortisol production. AB - Cortisol is a well-known immunosuppressant when used therapeutically. The present investigation was set out to study if diurnal variations in endogenous cortisol production are reflected by changes in proliferative responses of human lymphocytes to either a mitogen (phytohemagglutinin-A, PHA) or an antigen (tetanus toxoid, TT) stimulus. The study included eight healthy volunteers. Blood was withdrawn at 0200, 0600, 1000, and 1800h for preparation of lymphocytes and determination of cortisol in plasma. Isolated cells were incubated without (baseline activity) or with inclusion of either 1 micrograms PHA or 10 micrograms TT. Proliferation was measured by labelling with 3H-thymidine for 16 h of culture. The cortisol plasma levels exhibited the well known diurnal variations with highest concentrations at 1000h and lowest levels at 0200h. Baseline activity or PHA stimulated cell proliferation did not show significant diurnal fluctuations. The response to TT, however, decreased by 38% between 0600 and 1000h (p = .01). Correlation analyses revealed that the reduction of the proliferative responses to TT correlated significantly (p < .05) with increases in cortisol plasma levels. It was concluded that diurnal fluctuations in the production of endogenous cortisol might be relevant for daytime dependent variations in immune responsiveness. PMID- 7777663 TI - Pulmonary dirofilariasis: first reported case in Puerto Rico. AB - The first case of human pulmonary dirofilariasis in our country is reported. The etiopathogenesis and pathological findings of the zoonosis are discussed. PMID- 7777664 TI - Acquired nevus flammeus. AB - This is the case of a 55-year-old male with cirrhosis who required a LeVeen shunt for relief of refractory ascites. After eight months he developed recurrence of the ascites and a erythematous patch around the surgical scar. Skin biopsy revealed a proliferation of small and medium-sized vessels throughout the dermis. The acquired form of nevus flammeus is rare an is usually preceded by trauma. This is the report of a patient with an acquired nevus flammeus associated to an obstructed peritoneovenous shunt. PMID- 7777665 TI - RCMI International AIDS Symposium. AIDS in Hispanic and Other Minority Populations. San Juan, Puerto Rico, November 3-4, 1994. Abstracts. PMID- 7777666 TI - Readmission in unstable angina. AB - To determine the characteristics of patients re-admitted after unstable angina (UA) pectoris, 120 consecutive patients hospitalized due to primary UA pectoris were prospectively studied 22 +/- 3 months after discharge. The patients were grouped based on the readmission rate. Those in group A (50) had recurrent admissions (mean 2.6, range 2 to 5). Seventy patients (group B) did not have readmissions during the follow-up period. All patients underwent coronary angiogram and symptoms-limited exercise stress test before discharge. The univariate characteristics for readmission were: age over 70 years (p = 0.02), nondiagnostic exercise stress testing (p = 0.03), angiographically diffuse coronary artery disease (p = 0.004), and non-interventional management (P < 0.001). Patients readmitted had increased incidence of myocardial infarction (p = 0.004) but similar survival at 2 years. By regression analysis, important variables for readmission were non-interventional management (Chi-Square = 7.6, p = 0.01), non diagnostic treadmill test (Chi-Square = 6.9, p = 0.03) and diffuse coronary artery disease (Chi-Square = 6.2, p = 0.04). It is concluded that in the interventional era the most important factor for readmission after primary UA pectoris is non-interventional management. Coronary revascularization should not be denied solely on the basis of age. PMID- 7777667 TI - Pulmonary factors limiting exercise capacity in patients with heart failure. AB - Patients with heart failure are frequently limited by exertional dyspnea. The mechanisms underlying dyspnea in these patients remain unclear. In this review, the pathologic changes that occur in the lung as a consequence of chronic pulmonary venous hypertension, pulmonary function test abnormalities, and potential mechanisms for dyspnea including airflow obstruction and/or respiratory muscle dysfunction are discussed. PMID- 7777668 TI - Cellular adaptations of the myocardium to chronic exercise. AB - The heart responds positively to programs of chronic dynamic exercise. Hallmark adaptations of the heart include a training bradycardia, increases in end diastolic dimension and maximal stroke volume, and a general improvement in ventricular performance and contractile function. Of considerable clinical significance are the general observations that chronic exercise renders the myocardium less susceptible to the deleterious effects of acute ischemic episodes and can effectively prevent and/or reverse many of the cardiac functional deficits that are known to occur in settings of chronic hypertension, advanced age, and myocardial infarction. In the text that follows, information gathered over the last 25 to 30 years has been reviewed in an attempt to identify cellular myocardial adaptations, both known and hypothetical, that are responsible for the observed effects of chronic dynamic exercise on the function and morphology of the heart in both normal and selected pathophysiologic settings. Finally, a variety of unresolved issues regarding the ability of chronic exercise to elicit adaptive cardiocyte responses has been identified. In so doing, it is hoped that creative thought and future work in the area will be stimulated. PMID- 7777671 TI - Sotalol: a new beta-adrenergic blocker for ventricular arrhythmias. AB - Sotalol is a water-soluble, nonselective, beta-adrenergic blocker that was recently approved in oral form in the United States for the treatment of ventricular arrhythmias that are judged to be life-threatening. As a beta blocker, sotalol is unique in having additional class-III antiarrhythmic activity. It is still not resolved whether sotalol is more effective than other beta-blockers in managing arrhythmias, but there are suggestions that it might possess greater antiarrhythmic and life-protecting activities than other types of antiarrhythmic drugs. The drug is well tolerated, but, because of its electrophysiologic activity, there is a small risk of proarrhythmia, specifically the development of polymorphic ventricular tachycardia and torsade de pointes. PMID- 7777669 TI - Neural regulation of sympathetic nerve activity in heart failure. AB - One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. A correlation between plasma norepinephrine and the severity of the heart failure state has been demonstrated. One mechanism that has been proposed to account for this sympathoexcitation is a depression in the baroreflex and, perhaps, cardiac reflex control of sympathetic nerve activity. This review summarizes work from several laboratories, including our own, that documents a depressed baroreflex control of heart rate and sympathetic nerve activity in both animals and humans with heart failure. The mechanism of the depressed baroreflex most likely is caused by reduced baroreceptor sensitivity as well as enhanced input to the central nervous system from cardiac receptors that are chemosensitive. Although sympathetic tone and arterial baroreflex sensitivity are altered in heart failure, there have been no studies showing a cause-and-effect relationship. Increases in plasma norepinephrine are similar in baroreceptor-denervated and intact dogs paced into heart failure. This latter observation cells into question the traditional concept of baroreceptor-mediated increases in sympathetic tone in heart failure. PMID- 7777670 TI - Optimal use of coronary care units: a review. AB - Patients at a low probability of acute cardiac pathology constitute a considerable proportion in many coronary care units (CCUs), such that physicians should consider more effective alternatives than CCU admission "to rule out myocardial infarction." In this article, strategies to increase the efficiency of managing patients with acute chest pain are reviewed. Algorithms aiming to improve the diagnostic accuracy of the general practitioner have been developed but require an electrocardiogram recorded at the home of the patient. Another method of triage encompasses the identification in the emergency room of the hospital of patients at a low probability of acute cardiac pathology by using predictive models that include laboratory assessments. A third strategy includes alternatives to CCUs for patients at a low risk of acute cardiac pathology, such as the creation of a simple observation unit. Finally, some investigators have sought to identify patients with good prognosis for early transfer from the CCU to lower levels of care. It is concluded that a combination of these approaches will be most efficient, and that the most appropriate choice will be determined by local circumstances. PMID- 7777672 TI - Teeth and tooth nerves. AB - (1) Although our knowledge on teeth and tooth nerves has increased substantially during the past 25 years, several important issues remain to be fully elucidated. As a result of the work now going on at many laboratories over the world, we can expect exciting new findings and major break-throughs in these and other areas in a near future. (2) Dentin-like and enamel-like hard tissues evolved as components of the exoskeletal bony armor of early vertebrates, 500 million years ago, long before the first appearance of teeth. It is possible that teeth developed from tubercles (odontodes) in the bony armor. The presence of a canal system in the bony plates, of tubular dentin, of external pores in the enamel layer and of a link to the lateral line system promoted hypotheses that the bony plates and tooth precursors may have had a sensory function. The evolution of an efficient brain, of a head with paired sense organs and of toothed jaws concurred with a shift from a sessile filter-feeding life to active prey hunting. (3) The wide spectrum of feeding behaviors exhibited by modern vertebrates is reflected by a variety of dentition types. While the teeth are continuously renewed in toothed non-mammalian vertebrates, tooth turnover is highly restricted in mammals. As a rule, one set of primary teeth is replaced by one set of permanent teeth. Since teeth are richly innervated, the turnover necessitates a local neural plasticity. Another factor calling for a local plasticity is the relatively frequent occurrence of age-related and pathological dental changes. (4) Tooth development is initiated through interactions between the oral epithelium and underlying neural crest-derived mesenchymal cells. The interactions are mediated by cell surface molecules, extracellular matrix molecules and soluble molecules. The possibility that the initiating events might involve a neural component has been much discussed. With respect to mammals, the experimental evidence available does not support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777674 TI - Spatially selective firing properties of hippocampal formation neurons in rodents and primates. PMID- 7777673 TI - Hippocampal markers of age-related memory dysfunction: behavioral, electrophysiological and morphological perspectives. PMID- 7777675 TI - [Roles of phospholipase D in cell functions and its regulatory mechanisms]. PMID- 7777676 TI - [Biological significance of lipid modifications of G-proteins]. PMID- 7777678 TI - [Biochemical studies of magnetotactic bacteria]. PMID- 7777677 TI - [Areal specification of the cerebral cortex]. PMID- 7777679 TI - [The current view of molecular biology of DNA tumor virus]. PMID- 7777680 TI - [Postoperative lesions of the peripheral nerves. 8 years' analysis]. AB - Damage to a plexus or peripheral nerve is a rare and avoidable complication of surgical anesthesia. We reviewed 2,750 case histories of patients who underwent surgery between 1985 and 1992, finding 6 cases of nerve lesions presenting postoperatively. Sequelae involved 1 abdomino-genital neuralgia, 1 case of post epidural radicular pain, 2 cases of peroneal nerve palsies and 2 of cubital paresis. Three of these cases were related to position during surgery, 1 to position during a prolonged period in bed in the intensive care unit, 1 to the anesthetic technique and 1 to surgical manipulation. Our data are important given the difficulty of studying the incidence of such cases due to patient dispersion and the loss of records of possible occurrences. The mechanisms by which lesions are produced are sometimes difficult to pinpoint but all are generally preventable. PMID- 7777682 TI - [Accidental perforation of the dural sac with a spinal needle introducer]. PMID- 7777681 TI - [Level of information on prices in an anesthesia department]. AB - The rationalization of health care spending has high priority in these times of economic difficulty. Anesthesiologists can contribute to more efficient use of resources and therefore must be well aware of the cost of the products they use. This study aims to evaluate their knowledge of the cost of commonly used products. Seventy-eight anesthesiologists with varying levels of experience and from different levels in the hierarchy were questioned about the cost of 20 products, drugs and disposable items commonly used in their work. The physicians were within 50% of the real price of 4 of the 11 drugs studied and were 100% right about 3 drugs. The respondents were 100% correct about 2 of the disposable items studied but did not give estimates within 50% of real cost for any of the remaining 7 items. Neither position in the hierarchy nor years of experience was related to degree of correctness in pricing the products studied. Awareness of the prices of commonly used products, particularly of disposable material, was low in the population of anesthesiologists studied. PMID- 7777683 TI - [Anesthesia from the patient's point of view]. PMID- 7777684 TI - [Severe hypophosphatemia and coma in a critically ill patient]. PMID- 7777685 TI - [Subarachnoid block for ovariectomy in a patient with pulmonary lymphangioleiomyomatosis]. PMID- 7777686 TI - [Quality of health care in anesthesiology and resuscitation]. PMID- 7777688 TI - [Quality control in anesthesiology]. AB - The process of quality control and auditing of anesthesiology allows us to evaluate care given by a service and solve problems that are detected. Quality control is a basic element of care giving and is only secondarily an area of academic research; it is therefore a meaningless effort if the information does not serve to improve departmental procedures. Quality assurance procedures assume certain infrastructural requirements and an initial period of implementation and adjustment. The main objectives of quality control are the reduction of morbidity and mortality due to anesthesia, assurance of the availability and proper management of resources and, finally, the well-being and safety of the patient. PMID- 7777687 TI - [Postoperative infection and anesthesia: analysis of various risk factors]. AB - OBJECTIVES: To study the possible relation between anesthetic techniques and other perioperative circumstances and factors and the presentation of infections after surgery. PATIENTS AND METHODS: We studied 22 patients who suffered infections after surgery and 54 who did not, analyzing the anesthetic technique used as well as other data on age, sex, concomitant disease, toxic habits, practice of invasive procedures, duration and nature of the surgical procedure and the use of antibiotic prophylaxis. Multivariate analysis (logistical regression) was performed in order to identify independent risk factors. RESULTS: None of the anesthetic techniques studied was associated with greater frequency of postoperative infection. Infected patients were significantly older than uninfected patients (75 +/- 9 years versus 61 +/- 18 years). Likewise the number of infections was higher among ASA III and IV (n = 20) patients than among ASA I and II (n = 2). The duration of surgery for infected patients was 4.15 +/- 2.12 hours whereas it was 2.87 +/- 1.86 hours (p < 0.001) for uninfected patients. Placement of a urinary catheter, repeated surgery, diabetes and blood transfusion all signified greater risk of infection, as did prophylaxis with second and third generation cephalosporins (OR = 12.5; 95% CI = 1.8-85.6) or tobramycin (OR = 66.4; 95% CI = 3.5-1,270). CONCLUSION: The risk of postoperative infection increases with age and poor physical status of patients (ASA III and IV), with diabetes, repeated surgery, transfusion of blood products and prophylaxis with third generation cephalosporins and tobramycin. PMID- 7777690 TI - [Pneumology Society of French Language. List of members 1995]. PMID- 7777689 TI - [Failure of the central oxygen supply to a surgical area. Analysis of a critical incident]. AB - An incident involving central oxygen supply failure affecting 4 anesthetized patients in the operating theatre was analyzed by way of interviews with the anesthesiologists and a review of graphic records of anesthesia. The 4 ventilators involved had been checked by each anesthesiologist according to his own method. The oxygen supply failure alarm warned of the supply cutoff in 2 cases and the oxygen analyzer detected the other 2 within approximately 1 minute. After the failure, 2 patients were ventilated with ambient air through the ventilator, 1 was given medicinal air with the resuscitator. None suffered damage or recalled having awakened as a result of the incident. The cause of the failure in oxygen supply has not been determined but its duration has been estimated to be between 4 and 7 minutes. Our investigation shows that: 1) the operating rooms are not equipped with an alarm that warns of a drop in pressure within the tubes that supply central oxygen and in 2 cases the alarm warning of a cutoff in oxygen supply to the respirator did not sound correctly; 2) the ventilator equipment check did not follow a standard method and did not cover the possibility of oxygen supply failure, and 3) no alternative oxygen supply is available inside the operating theatre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777691 TI - Editor's viewpoint: do you know the way to San Jose? PMID- 7777692 TI - A comparison of grip strength and selected psychomotor performance measures in healthy and frail elderly females. AB - Researchers have examined the relationships between strength and psychomotor skills among healthy male subjects far more thoroughly than among female subjects, especially elderly females. The purpose of the present investigation was to compare healthy and frail elderly females on grip strength and psychomotor performance measures. Nineteen healthy elderly females (M = 75.7 years of age) and 20 frail elderly females (M = 80.5 years of age) performed simple aiming movements in order for the investigators to obtain psychomotor measures (e.g., reaction time, movement time, kinematic movement characteristics). In addition, strength measures were obtained in the dominant and nondominant hands. Significant differences were found between elderly females on grip strength and psychomotor performance measures. In general, healthy subjects were stronger and exhibited superior control of movements (e.g., greater impulse, fewer movement adjustments). PMID- 7777693 TI - Imaging goal-directed movement. AB - The main purpose of the present investigation was to determine how Shepard's (1968) second-order isomorphic principle relates to imaging goal-directed movement. Reports of movement times for actual and imaged movements were obtained using Fitts-type tapping tasks. Displays consisted of two different (referential) or two identical (nonreferential) stimulus pairs. In Experiments 1a and 1b, target width and amplitude were manipulated to produce two indexes of difficulty. In Experiments 2a and 2b, the index of difficulty was constant, and biases were created by indicating that movement time increased with decreases in target width or increases in amplitude. In all four experiments, reported movement time reflected Fitts' (1954) law for actual tapping and during early trials for referential imagery. In Experiments 1a and 1b, reported movement times for the two indexes of difficulty were similar for nonreferential imagery and at later trials for referential imagery. In Experiments 2a and 2b, reported movement times reflected the biases for nonreferential imagery and at later trials for referential imagery. The results suggest that propositional knowledge and information processing interact to control movement imagery. PMID- 7777694 TI - Skill-related task structures, explicitness, and accountability: relationships with student achievement. AB - The purpose of this study was to determine relationships of task structures, explicitness, and accountability with student achievement in physical education. The subjects were teachers of 10 physical education classes and their 202 students. Each class participated in instruction that was videotaped, and the students were pre- and posttested. Videotapes were coded to collect data on each skill-related task including the task presentation time, skill being taught, explicitness of the task presentation, primary and secondary accountability systems used, level of student participation, and total task time. Among the many results, for the volleyball forearm pass, significant relationships were found for the total number of tasks and time spent in tasks when expectations included outcome, situation, and criteria-product. For the volleyball underhand serve, significant relationships were found for the total number of tasks and time spent in tasks when accountability included teacher feedback with follow-up and monitoring of off-task behavior. PMID- 7777695 TI - Teachers' value orientations in urban and rural school settings. AB - The purpose of this research was to describe physical educators' value orientations for curricular decision making in urban and rural teaching settings. The revised Value Orientation Inventory (Ennis & Chen, 1993) was used to collect data from 495 physical educators in urban and rural districts. Data were analyzed descriptively using a full-design and a nested MANOVA model. Results indicated that teachers in urban school districts placed a higher priority on self actualization and social responsibility than did teachers in rural school districts. Conversely, teachers in rural school districts placed a higher priority on disciplinary mastery and learning process than did their colleagues in urban schools. The discussion focused on differences in school contexts in urban and rural schools. Teachers appeared to shape their curriculum to reflect the opportunities and constraints within their school settings. PMID- 7777696 TI - Effects of goal-setting interventions on selected basketball skills: a single subject design. AB - The purpose of this investigation was to examine the effects of a goal-setting intervention program on selected components of basketball performance over the course of a competitive season. A multiple-baseline, single-subject design was used with baseline observations on various performance components (e.g., turnovers, rebounds), collected for four elite college basketball players during their first eight games of the season. At the midseason break, these players selected one aspect of their play that they felt would benefit from improvement. A goal-setting program was designed based on the goal attainment scaling procedure recommended by Smith (1988), whereby subjects generated numerical targets for their chosen components. Performance components were then assessed for the next eight games as they had been in the preintervention phase. Following the intervention, 3 of the 4 subjects showed consistent improvements in their targeted areas of performance. Also, there were no outcome changes in the performance components that weren't targeted by the subjects. The findings suggest that future studies may benefit from achieving greater ecological validity and utilizing alternative designs to the traditional nomothetic approaches which may tend to mask positive intervention effects on certain individuals. PMID- 7777697 TI - Brain slow potentials reflecting successful shooting performance. AB - Preparatory brain activity from frontal, centro-lateral, and occipital areas were recorded from top-level rifle shooters during shooting performance. The aim of the study was to examine the relation of brain slow potentials to qualitative (rifle holding) and quantitative (hit) aspects of superior shooting performance. For this purpose, a typology of slow potentials (SPs) was developed. The resulting SP types were used for unraveling the associations between the electrocortical activity and behavioral output. The main finding was that frontal positivity was associated with successful performance, but only if the central right SP was more negative than the central-left one. This finding was explained as showing that, in the case of superior performance, a shooter is able to refrain from irrelevant motor activity (frontal positivity) and concomitantly concentrate on the visual-spatial processing (right-sided negativity). In all, the present experiment suggests that the SPs are consistently related to the covert aspects of shooting performance, which lack an overt manifestation. At the practical level, this means that the SPs provide a tool for accessing information concerning the optimal balance between visual-spatial targeting and motor activity which can make a valuable contribution to the understanding of superior shooting performance. PMID- 7777698 TI - The paradox of the contented working woman in intercollegiate athletics administration. AB - We investigated the paradox of the contented working woman among middle and first line intercollegiate athletics administrators. In this paradox, women report lower salaries than men but express comparable job satisfaction. The sample comprised 143 women and 371 men in 106 National Collegiate Athletic Association (NCAA) Division I-A institutions. Job satisfaction was measured with the Job Descriptive Index (Smith, Kendall & Hulin, 1969) and Job in General (Ironson, Smith, Brannick, Gibson & Paul, 1989) scales. Analyses revealed the existence of the paradox: Women were paid significantly less, but were equally satisfied with their jobs. Neither gender was satisfied with promotion opportunities or pay, but both were highly satisfied with their jobs in general--another apparent paradox. The disproportionate number of male respondents raised questions about gender equity in athletics administration. PMID- 7777699 TI - Allometric scaling of grip strength by body mass in college-age men and women. PMID- 7777700 TI - The effects of a physical fitness program on low-fit children. PMID- 7777702 TI - Persistent increased lung response to methacholine after normobaric hyperoxia in rabbits. AB - This study was performed to determine the occurrence and time course of airway hyperreactivity following exposure to normobaric hyperoxia. Twenty-six rabbits were studied. Twelve served as control (group 1), and 14 were exposed to normobaric hyperoxia (FiO2 > or = 95%) for 48 h: 9 rabbits (group 2) were studied after 1 day of recovery in room air and 5 (group 3) after 7 days. The rabbits were anesthetized, curarized and artificially ventilated. Respiratory resistance (Rrs) and elastance (Ers) and their respective changes induced by cumulative doses of aerosolized methacholine were assessed by the multiple linear regression analysis of airway pressure, tidal flow and volume. Weight-specific Rrs and Ers were significantly higher in group 2 (respectively, 87.7 +/- 6.5 cmH2O.L-1.sec.kg and 1100.2 +/- 87.1 cmH2O.L-1.kg, mean +/- SEM) than in group 1 (respectively, 65.2 +/- 3.2 cmH2O.L-1.sec.kg and 904.4 +/- 49.7 cmH2O.L-1.kg (P < 0.05)), but were not different from group 3 (79.4 +/- 7.9 cmH2O.L-1.sec.kg and 952.3 +/- 125.0 cmH2O.L-1.kg, respectively). The dose of methacholine required to increase Rrs by 50% (PDRrs50) was significantly lower in both treated groups: 0.37 +/- 0.11 mg in group 2 and 0.51 +/- 0.19 mg in group 3 vs 2.07 +/- 0.51 mg in group 1 (P < 0.05)). PDErs50 was significantly lower in group 2 (0.45 +/- 0.15 mg) and 3 (0.75 +/- 0.43 mg) compared with controls (1.11 +/- 0.26 mg (P < 0.05)). These results show that hyperoxia induces an increase in Rrs and Ers, and airway hyperreactivity in the rabbit. The latter is prolonged beyond the immediate post exposure period. PMID- 7777703 TI - Ventilatory sensitivity to single breaths of CO2 around the control point in man. AB - We used single inspiratory capacity breaths of 5, 6 or 8% CO2 in air to obtain ventilatory responses in normal subjects, with ensemble averaging of repeated runs to define stimulus and response (Protocol 1). We also compared the effect of an inspiratory capacity (IC) breath of 8% CO2 with that of two tidal volumes (TV) at the same concentration (Protocol 2). The ventilatory response was defined first as the ratio of peak changes in ventilation and end-tidal PCO2, and secondly by the ratio of their integrals. We obtained group mean values of 0.21 L min-1 mmHg-1 for the peak method and 0.80 L min-1 mmHg-1 for integrals (Protocol 1). There was no significant difference between IC and TV response values (Protocol 2) either by the peak method (0.17 vs 0.19 L min-1 mmHg-1) or by integrals (0.47 vs 0.53 L min-1 mmHg-1). A significant decrease in ventilation was seen in the second tidal volume 8% CO2 breath, even though the stimulus was unperceived by four out of five subjects. CO2 responses can be obtained from these techniques, but the necessary analysis is too cumbersome for general use. Taking a deep breath had no detectable separate effect, but CO2 in the airway may depress ventilation even at concentrations which the subject cannot detect. PMID- 7777701 TI - Cellular mechanisms of hypoxia-induced contraction in human and rat pulmonary arteries. AB - The effect of hypoxia was investigated in human (HPA) and rat (RPA) pulmonary arteries. Hypoxia-induced contraction was 95 +/- 8.7% and 9.3 +/- 4.8% of the control response to K(+)-rich (80 mM) solution in HPA and RPA, respectively (n = 10). When RPA strips were precontracted with phorbol 12,13 dibutyrate (0.2 microM), hypoxia elicited a larger contraction (105 +/- 13.4% of the control response, n = 8). In both types of artery, hypoxia-induced contraction was dependent on the extracellular calcium concentration (66 +/- 8.4% and 40 +/- 14.4%, reduction for 1.25 mM Ca2+ in HPA and RPA, respectively, n = 6) and was inhibited by verapamil (0.05-10 microM) and nifedipine (0.05-1 microM). Glibenclamide (5-10 microM) increased the amplitude of hypoxia-induced contraction (+42 +/- 5.3%, n = 5). Hypoxia-induced contraction was blocked by cromakalim (1 microM) and this effect was reversed by glibenclamide (5 microM). This contraction was also inhibited by iodoacetic acid (250 microM). In beta escin skinned pulmonary arterial strips, hypoxia had no effect on the calcium concentration-tension relationship. These results suggest that the O2 sensor in the pulmonary artery is located on the vascular smooth muscle plasmalemma. Hypoxia-induced contraction is dependent on calcium influx through voltage sensitive calcium channels. Its amplitude is modulated by the functioning of potassium channels. PMID- 7777704 TI - Effects of carotid body sympathetic denervation on ventilatory acclimatization to hypoxia in the goat. AB - Our objective was to test the hypothesis that diminishing sympathetic input to the carotid body (CB) during prolonged exposure to hypoxia results in increased CB afferent activity and increased ventilatory drive. Six awake goats were studied prior to and following sectioning of the efferent sympathetic input to the CB from the superior cervical ganglion. Ventilatory responses to acute and prolonged isocapnic hypoxia (PaO2 40 Torr) and drugs (norepinephrine and dopamine, 0.5, 1.0 and 5.0 micrograms.kg-1 min-1) were collected prior to the denervation. One week and 3-4 weeks following the sympathetic denervation, the animals were restudied following the above protocol. Ventilation was significantly lower following sympathetic denervation in normoxia and during the hypoxic exposure. However, the response to acute hypoxia and the time-course of ventilatory acclimatization to hypoxia was not altered by sympathetic denervation. All doses of norepinephrine and dopamine significantly inhibited VE in a dose-dependent manner. Sympathetic denervation did not significantly alter the response to the drug infusions. The sympathetic innervation to the CB does not appear to play a role in either the acute or prolonged ventilatory responses to hypoxia in the awake goat, but may affect overall ventilation. PMID- 7777705 TI - Oxygen enrichment of room air to relieve the hypoxia of high altitude. AB - Recently there has been increasing commercial activity at altitudes of 3500-6000 m. Examples include new mines in northern Chile at altitudes of about 4500 m. Because the workers come from sea level, intolerance of the high altitude is a major problem. This degree of hypoxia reduces work capacity, mental efficiency and sleep quality. One novel solution is to raise the PO2 of the room air by adding oxygen to the room ventilation. This is remarkably effective. For example, at altitudes of 4000-5000 m, increasing the O2 concentration by 1% (e.g. from 21 to 22%) reduces the equivalent altitude by about 300 m. Thus raising the O2 concentration by 5% at the new mines reduces the equivalent altitude to 3000 m which is easily tolerated. The introduction of oxygen concentrators (molecular sieve) which require only electrical power makes O2 enrichment feasible. The fire hazard is less than in air at sea level. Everybody now expects that the ventilation of a room will provide a comfortable temperature and humidity. Control of the oxygen concentration can be regarded as a further logical step in man's control of his environment. PMID- 7777706 TI - Hemoglobin function in a skin-breathing aquatic salamander, Desmognathus quadramaculatus. AB - Adult black-bellied salamanders (Desmognathus quadramaculatus) were maintained in humidified gas at 12 degrees C. Hypoxic salamanders were exposed to 8.1-9.6% O2 for 10-11 days; normoxic animals were maintained in air (20.9% O2). Hypoxia acclimation had no effect on blood O2 affinity, O2 equilibrium curve shape or CO2 Bohr effect. At pH 7.7, P50 values for hypoxic and normoxic salamanders were 28.2 +/- 0.4 and 28.6 +/- 0.8 Torr, respectively. Hill plots were curvilinear for both treatments; Hill's n increased from values of 2.1-2.2 below 40% saturation (S) to 2.6 above 50% S. CO2 Bohr slopes (delta log P50/delta pH) were -0.19 +/- 0.01 and -0.23 +/- 0.02 for hypoxic and normoxic animals, respectively. Resting MO2 for a separate group of normoxic salamanders fell into two categories; low MO2 (1.46 +/ 0.16 mumol.g-1.h-1) and high MO2 (3.51 +/- 0.52) animals. Exposures to 5 and 25% CO had no effect on MO2 of low metabolism Desmognathus, but reduced MO2 of high metabolism animals to levels similar to the low MO2 group. Hb-O2 binding results suggest that D. quadramaculatus blood is ideally suited for respiratory O2 exchange during normoxic activity. While submerged and inactive, hypoxic boundary layers surround the skin-breather. Contributions of Hb during hypoxic inactivity may be to augment O2 content and increase blood buffering capacity. PMID- 7777707 TI - Effects of carbonic anhydrase inhibition on the acid base status in lamprey and trout. AB - Inhibition of red cell carbonic anhydrase (CA) activity resulted in the rapid development of a respiratory acidosis (0.25 pH depression within 15 min post injection) in the blood of trout. In the lamprey, however, the onset of the respiratory acidosis was delayed and its magnitude was less (0.18 pH depression at 6 h post-injection). Erythrocyte pH of both species decreased by about 0.12 units by 1 h after CA inhibition. These data, combined with the lack of rapid anion (Cl-/HCO3-) exchange in the red cells of agnathans but not in other lower vertebrates, support the hypotheses that (1) the majority of total CO2 in lamprey is transported within the erythrocyte, and (2) the limiting step in the evolution of a functioning Jacobs-Stewart cycle, and thus the evolution of the common mechanism of systemic CO2 transport in vertebrate blood, was the incorporation of the band-3 anion exchange protein into the membrane of the red cell. PMID- 7777709 TI - Factors limiting maximal O2 consumption: effects of acute changes in ventilation. AB - The response of the O2 transport system to acute changes in alveolar ventilation (VA) was analysed. The fractional limitations to maximal O2 consumption (VO2max) imposed by the lungs (ventilation, FV, and lung-blood transfer, FL), the cardiovascular system (FQ), and peripheral O2 diffusion (Fp) were calculated according to a multifactorial model. A reference set of data, describing the status of O2 transport at maximal exercise in normoxia was used. The effects of VA on VO2max were assessed on the assumption of a constant reference O2 flow in mixed venous blood (QVO2). The changes in reference data after given independent changes in VA were calculated by an iterative procedure, until the VO2max value compatible with the constant reference QVO2 was found, at PIO2 values of 150 (normoxia), 130, 110 and 90 Torr. The VO2max changes in normoxia were less than expected assuming a linear O2 transport system, because of the flatness of the O2 dissociation curve around normoxic PO2. This affected the cardiovascular resistance to O2 flow, and its changes counterbalanced the effects on VO2max of induced changes in VA. This phenomenon was reversed in hypoxia, as the steep part of the O2 dissociation curve was approached. The fractional limitations to VO2max in normoxia resulted as follows: FV and FL provided between 5 and 12%, FQ between 59 and 78%, and Fp between 13 and 19% of the overall VO2max limitation. In hypoxia, FV and FL increased and FQ decreased. At PIO2 = 90 Torr, when VA was halved, FV, FL, FQ and Fp amounted to 0.35, 0.31, 0.20 and 0.14, respectively. PMID- 7777708 TI - Effect of phorbol myristate acetate-induced lung injury on airway blood flow. AB - The effects of phorbol myristate acetate (PMA) induced lung injury on the pulmonary and systemic blood flow contributions to the trachea and main bronchi (upper airways) were assessed in anesthetized dogs by injecting 15 microns radiolabeled microspheres into the right and left heart, respectively. Upper airway blood flow was studied in lungs given the following treatments: (1) PMA; (2) PMA in lungs pretreated with the thromboxane synthetase inhibitor OKY-046, and (3) PMA in lungs pretreated with the antioxidant catalase. After microsphere injections, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The results of this study indicate that under normal conditions, tracheal mucosa [33-52 ml.min-1.(100 g)-1] and tracheal cartilage [18-27 ml.min 1.(100 g)-1] blood flow is primarily systemic while both the systemic [12-18 ml.min-1.(100 g)-1] and pulmonary [6-12 ml.min-1.(100 g)-1] circulations contribute substantial amounts of blood flow to the main bronchi. PMA significantly decreased the systemic blood flow contribution to the tracheal cartilage and muscle-mucosa, and both the systemic and pulmonary blood flow contributions to the main bronchi to less than 50% of control values, an effect that was inhibited by catalase, but not by OKY-046. These results suggest that the effect of PMA-induced lung injury on the pulmonary and systemic blood flow contributions to the upper airways is at least partially mediated by oxygen radical production, probably hydrogen peroxide (H2O2), but not by the production of the arachidonic acid metabolite thromboxane. PMID- 7777710 TI - Gas conductance and metabolism of shorebird eggs: variation within and between species. AB - Fresh egg mass (M0; g), water vapor conductance of the egg shell (GH2O; mg.[Torr.d]-1), and neonate mass (Mn; g) were measured in the ruff (Philomachus pugnax), common redshank (Tringa totanus), northern lapwing (Vanellus vanellus), black-tailed godwit (Limosa limosa), and Eurasian curlew (Numenius arquata). In addition, the development of embryonic O2 consumption (MO2; ml.d-1) and CO2 production (MCO2; ml.d-1) were measured in these species, except the ruff. In northern lapwing and black-tailed godwit eggs the coefficients of variation for GH2O were 3.8 and 2.3 times higher, respectively, than those for M0. In these two species only about 10% of the variation for GH2O was attributable to M0, and about 77% to differences between clutches, suggesting a strong maternal component. In the northern lapwing, embryonic MO2 plateaued prior to internal pipping, but not in the common redshank and black-tailed godwit. The latter result is in contrast to embryonic patterns previously described for other precocial species. In shorebirds the occurrence of an embryonic MO2 plateau is not related to the neonatal level of cold-induced thermogenesis. PMID- 7777711 TI - [Trends in thyroid surgery at the Instituto Nacional de la Nutricion Salvador Zubiran]. AB - The diagnosis and treatment of thyroid disease has significantly changed with time. With the aim of analysing changes in thyroid surgery in our institution, a representative sample of patients from the first three years in four decades (1960-1992) were comparatively analysed. In the sixties, the diagnosis of thyroid cancer was made during surgery; by contrast, this diagnosis was correctly done by fine needle aspiration (FNA) in most patients of the last decade. Thyroid lobectomy, infrequently used in the treatment of differentiated thyroid carcinoma in earlier times, has now been abandoned and currently most patients undergo total or near-total thyroidectomy. Complications such as hypoparathyroidism and recurrent laryngeal nerve paralysis have importantly decreased with time and were not seen in the last decade. A trend toward an earlier diagnosis of thyroid carcinoma was also observed. In summary, the number of thyroidectomies for benign diseases has been importantly reduced by the use of FNA with the proportional increment of surgery for malignant disease. PMID- 7777712 TI - [Response of insulin and C-peptide to a mixed meal in non-insulin-dependent diabetics treated with insulin and chlorpropamide]. AB - Glucose control in NIDDM is prone to progressive deterioration due to secondary failure to oral hypoglycemic therapy. Insulin may subsequently be required for optimal control in spite of peripheral hyperinsulinemia. In Mexico, diabetes associated with obesity is common. We therefore designed a prospective study combining insulin and chloropropamide in order to evaluate any improvement in insulin response to a standardized meal load and a consequent amelioration of glucose control. METHODS. Twenty diabetic patients with secondary failure to full doses of hypoglycemic drugs and moderate hyperglycemia were recruited. Therapy was initiated with human insulin 20 IU/day and 500 mg cholopropamide, titrating insulin dosage in order to achieve euglycemia. Before treatment and at the end of the study period, a glucose/insulin/C peptide response curve to a mixed standardized meal was performed. Blood glucose, serum lipids fructosamine and glycosylated hemoglobin levels were also determined. All patients were followed by capillary glucose measurements three times a week and glucose and fructosamine concentrations every two weeks during the study period. RESULTS. All patients required less insulin, and glucose control improved significantly. Glucose, fructosamine and glycosylated hemoglobin levels decreased from 262 mg/dL, 369 mmol/L and 14% to 111 mg/dL, 252 mmol/L, and 8% respectively; all differences were statistically significant. Insulin and C peptide levels increased significantly from 22.2 mU/mL and 1.65 ng/mL to 29.8 mU/mL and 1.97 ng/mL, respectively. When we measured the area under the curve, total values improved from 110 and 7.69 to 127 and 9.37, respectively; this was also statistically significant. Lipids levels decreased significantly, including triglicerides, total and LDL cholesterol whereas HDL cholesterol levels increased. CONCLUSIONS. Glucose control improved in our patient cohort the pancreatic insulin response probably due to a more adequate glycemic microenvironment and a possible enhanced exogenous and endogenous insulin function. PMID- 7777713 TI - [Productivity before and after installing a computerized system in a clinical laboratory]. AB - A laboratory information system was installed on January 1991 in the clinical laboratory of the Instituto Nacional de Cancerologia. Our main objective was to speed up the administrative work and integrate its operations under one management. We evaluated the productivity before (1990) and after installing the system (1992), using the parameters proposed by the College of American Pathologists. In 1990 there were 30,764 patients who underwent 191,070 laboratory studies, resulting in 131 tests/clerk/day and 21 patients/clerk/day. In 1992 these figures were 43,679 patients, 245,280 tests, 168 tests/clerk/day and 30 patients/clerk/day. The productivity indexes showed a 41% increase in the number of patients and of 28% in the number of tests. In addition, the laboratory personnel started activities in teaching and research which had been non existent before, i.e. in 1992 they started three research projects and participated in three national or international scientific meetings. In summary, no additional personnel was required even though there was an increase in the workload, basically due to a more efficient organization of the work when using a computerized system. PMID- 7777715 TI - [Cystic neoplasms of the pancreas: report of 3 cases presenting diagnostic difficulties]. AB - Cystic tumors of the pancreas are rare, although their detection has become more frequent with the advent of imaging techniques. In most cases, surgical exploration and often resection of the cystic neoplasm is necessary for establishing a definitive diagnosis; resection remains the treatment of choice. This paper describes three patients who underwent surgery because of cystic tumors of the pancreas. Abdominal pain was the main clinical manifestation; abdominal CT showed the cystic tumor in all three cases. Surgical exploration and resection was successfully accomplished in all. The definitive histological diagnoses were serous cystadenoma, multicystic hamartoma, and choriocarcinoma metastatic to the head of the pancreas. To our knowledge, the last two are the first ones with such diseases reported in the literature. PMID- 7777714 TI - [Lymph node biopsy using fine-needle aspiration. Clinical and cytohistological correlation in 179 cases]. AB - We reviewed the institutional experience with fine needle aspiration biopsy (FNAB) of peripheral lymph nodes in the Instituto Nacional de la Nutricion Salvador Zubiran from January 1988 to December 1992. A total of 298 FNAB had been performed in 288 patients. Aspirates with just blood, few stromal cells or with desiccation changes were excluded (63 cases), as well as those in whom it was not possible to establish a clinical or morphologic correlation (56 cases). In the 179 cases included, the FNAB diagnosis was histologically confirmed in 137 and in 42 cases the correlation was established by clinical follow-up and response to treatment. According to the diagnosis, aspirates were divided in benign and malignant in the analysis. We observed 70 aspirates (39%) with benign lesions and 109 (61%) with primary or metastatic neoplastic cells. The most frequent benign diagnosis was hyperplasia followed by epithelial metastatic neoplasms. In 25 aspirates there was a discrepant cyto-histologic diagnosis but only six were false negatives. No false positive or complications were identified. The FNAB in our cases showed: sensitivity 95%, specificity 100%, positive predictive value 100% and negative predictive value 91.4%. Our data support the value of FNAB as a reliable, safe, inexpensive and easy to perform method in the diagnosis of lymph node enlargements. Thus, we believe this method should be recommended as the initial approach in the study of lymphadenopathies. PMID- 7777716 TI - [Hormone replacement therapy in the climacteric]. AB - Menopause is the physiologic state that is a consequence of the cessation of ovarian function. A large number of vasomotor, psychological and gynecological symptoms have been associated with menopause. Hormonal replacement therapy is effective in treating these conditions. The use of estrogens and progestins including dosages, routes of administration and their advantages and disadvantages are reviewed in this article. In addition, hormonal replacement therapy may reduce the risk of atherosclerosis and prevent the osteoporosis of climateric women. Hormonal therapy is associated with side effects but they do not contraindicate its use. PMID- 7777717 TI - [Medical attitude and legal concepts about some patient rights]. AB - OBJECTIVE: To explore medical attitudes toward some patient rights and some legal aspects involving medical practice in Mexico. DESIGN: Prospective, transversal and nonrandomized study using a multiple choice survey of 12 questions. SETTING: An urban general hospital in the city of Aguascalientes, Mexico. SUBJECTS: Seventy five physicians at the beginning of a specialty medical residency. MAIN MEASUREMENTS: They covered four areas: the patient's right to decide, the medical attitude of benefit to the patient above all considerations, the patient's capacity to make decisions, and some legal aspects of medical practice. RESULTS: 34% of the physicians gave the patient the right to decide, 34% were opposed, and 32% referred it to a third person; 26% showed a benevolent attitude to the patient, 69% did not and 5% referred it; 73% recognized the patient's capacity of decision and 27% did not; only 40% knew about legal aspects of medical practice. CONCLUSIONS: This study suggests an important lack of knowledge of the Mexican physicians in regard to patient rights and to legal aspects in medical practice. PMID- 7777718 TI - [Renal and extra-renal mechanisms of sodium and water retention in cirrhosis with ascites]. AB - In this work we analyze the renal and systemic factors involved in the sodium retention in two conditions: in extracellular volume depletion and in edema forming states, particularly liver cirrhosis with ascitis. In this paper we accept that the volume loss of body fluids stimulates the "effective arterial blood volume" (VAE). This term results from a decrease in the arterial blood volume secondary to a fall in cardiac output or a peripheral arterial vasodilatation. The reduction in the VAE stimulates: the high pressure baroreceptors (carotid sinus and aortic arch); the intrarrenal mechanisms, such as the yuxtaglomerular apparatus and the renin angiotensin aldosterone system; the sympathetic adrenergic system; the non osmotic release of antidiuretic hormone; prostaglandins (PGE1, Tromboxane) and endothelin; and inhibits the atrial natriuretic peptide. We also describe the sodium transport mechanisms along the nephron during physiological conditions and after volume depletion, and in edema formation states, specially hepatic cirrhosis with ascitis. We speculate that the intrarenal mechanisms are more important and persistent than the systemic mechanisms. It is possible that the sodium retention of these states might be the result of direct stimuli of the tubular sodium transport mechanisms in the different segments of the nephron, mediated by the co and counter transports, ATPase activity or by the second messengers cyclic AMP and cyclic GMP. The clonation and structural characterization of the different sodium transports may help us to establish, more precisely, the intracellular tubular mechanisms responsible for the tendency of the body to retain sodium. The amount of information generated in the future may help us to demonstrate, with more precision, the mechanisms responsible for the sodium retention and excretion in normal and pathological conditions, particularly the edema forming states such as cardiac failure, nephrotic syndrome and hepatic cirrhosis with ascitis. PMID- 7777719 TI - [Smoking and the "protective effect "]. PMID- 7777720 TI - [Essential thrombocythemia]. PMID- 7777721 TI - Endocrine causes of hypertension. AB - Hypertension is a prominent feature of various endocrine diseases including primary aldosteronism, pheochromocytoma (considered separately in this issue), Cushing's syndrome, adrenal enzymatic deficiencies like 11 beta-hydroxylase, 17 alpha-hydroxylase deficiencies, and congenital or acquired 11 beta-hydroxysteroid dehydrogenase deficiencies. Patients with 11 beta-hydroxylase deficiency cannot convert 11-deoxycortisol or deoxycorticosterone into the active glucocorticoids cortisol and corticosterone, respectively. The increase in the powerful mineralocorticoid deoxycorticosterone, resulting from the enzymatic block, promotes sodium retention, hypertension, and hypokalemia. Females who have the deficiency also show signs of virilization due to the shunting of the precursors to the synthesis of adrenal androgens. Patients with 17 alpha-hydroxylase deficiency present with hypertension and/or hypokalemia, and male members exhibit pseudohermaphroditism with no development of male sexual characteristics. The defect is due to the lack of 17-hydroxylated steroids, which are necessary precursors in the synthesis of androgens and estrogens. The hypertension is due to the accumulation of the mineralocorticoid deoxycorticosterone. The mineralocorticoid receptor derives its specificity from the co-expression of the 11 beta-hydroxysteroid dehydrogenase, which converts the active steroids corticosterone and cortisol to the inactive 11-dehydrocorticosterone and cortisone, preventing their interaction with the receptor. Congenital absence of the 11 beta-hydroxysteroid dehydrogenase or acquired deficiency induced by consuming licorice or its derivatives result in occupancy of the mineralocorticoid receptor by cortisol and corticosterone, and production of mineralocorticoid-type hypertension. PMID- 7777722 TI - Primary aldosteronism. AB - Primary aldosteronism occurs much more commonly than generally appreciated. Diagnosis is facilitated by measuring urinary aldosterone excretion in conjunction with determination of the level of plasma aldosterone suppression after infusion of 2,000 mL of normal saline over 4 hours. Multiple diagnostic procedures are required to determine the specific type of primary aldosteronism. Patients with aldosterone-producing tumors, unilateral adrenal hyperplasia, and primary adrenal hyperplasia are treated surgically, whereas those with bilateral zone glomerulosa hyperplasia and glucocorticoid-remediable aldosteronism are treated medically. PMID- 7777723 TI - Pheochromocytoma. AB - Although a rare cause of secondary hypertension, timely recognition and management of pheochromocytoma are crucial to prevent serious complications that can result from this tumor. The cause of pheochromocytoma is unknown. It may be a component of a polyglandular endocrine disturbance or associated with other neuroectodermal tumors, but usually it is recognized as an isolated finding. Because of the variable clinical manifestations, proper diagnostic quest for pheochromocytoma depends on a high index of suspicion. Availability of biochemical assays for catecholamines and their metabolites has improved our ability to establish or exclude the diagnosis of pheochromocytoma in a suspected patient. However, before ordering the biochemical tests, it is important to be certain that the patient has not taken any drugs or substances that can lead to a spurious value. Confirmatory localization of pheochromocytoma has become a straightforward exercise owing to current radiological techniques. Blockade of the effects of catecholamines provides the pharmacological basis for medical treatment of pheochromocytoma. Surgical removal of the tumor is the treatment of choice for most patients with pheochromocytoma. PMID- 7777725 TI - Renovascular hypertension. AB - Renovascular hypertension is one of the more common causes of secondary hypertension. The true prevalence of this condition is not known, because only a selected few with hypertension are considered for thorough diagnostic work-up. The higher incidence figures come from centers with a special interest in this disease. The ability of a clinician to detect renovascular hypertension has improved substantially, thanks to the advances in radiology. The predominant mechanism of blood pressure elevation from renal ischemia is activation of the renin-angiotensin system. Clinically, the pathological lesions that cause renal artery stenosis are atherosclerosis and fibromuscular dysplasia; the former is typically seen in older men, and the latter is typically found in young women. Suspicion of the presence of renovascular disease should prompt the physician to obtain appropriate screening and confirmatory tests. Once diagnosed, the management of patients with renovascular hypertension requires a carefully planned multidisciplinary approach to offer the patient a best possible therapeutic option, with surgical revascularization or balloon angioplasty, or chronic medical therapy. However, these options are not mutually exclusive. The best long-term results are obtained with surgical therapy. Although balloon angioplasty is being increasingly used perhaps as the preferred initial therapeutic procedure for many patients with renal artery stenosis, long-term results comparable with surgery are not yet available. The ideal rational therapy for patients with renal artery stenosis is reperfusion of the ischemic kidney either by surgical correction or by balloon dilation. The aim is not only to improve the blood pressure control, but also to prevent and at times to reverse renal failure. Although effective antihypertensive drugs have become available, the role of medical management of renovascular hypertension is shrinking and should be limited to patients who have contraindications to or unwilling to undergo corrective procedures to relieve renal ischemia. PMID- 7777724 TI - Renal parenchymal disease and hypertension. AB - Renal parenchymal disease is the most common cause of secondary hypertension, accounting for 2.5% to 5.0% of all cases. Hypertension associated with renal parenchymal disease occurs as a complication of a wide variety of glomerular and interstitial renal diseases and may accelerate the decline in renal function if inadequately controlled. Renal parenchymal hypertension most probably represents the combined interactions of multiple independent mechanisms: potential factors include impaired sodium handling leading to volume expansion, perturbations of the renin-angiotensin system, alterations in endogenous vasodepressor compounds, and possibly increased activity of vasoactive substances. The past several years have witnessed newer insights into both the pathophysiology and the therapeutics of this disorder. The characterization of endothelin and the nitric oxide (NO) arginine pathway and their roles in biology and medicine has provided additional new insights with regard to the pathogenesis of hypertension in renal parenchymal disease. For example, methylated L-arginine derivatives that possess NO synthase inhibitor capabilities including NG-N-dimethylarginine and N-monomethyl-L arginine are found in human plasma and in urine. Patients with chronic uremia have impaired elimination of these compounds, and circulating concentrations of these compounds may increase sufficiently to result in inhibition of NO production. Thus, accumulation of endogenous NO synthase inhibitors might contribute to the hypertension of advanced renal failure. Similarly, it has been proposed that increased endothelium-derived endothelin that results from hypertensive injury to vascular endothelium could lead to further vasoconstriction and worsening of hypertension. Additional insight into this fascinating problem must await further biochemical characterization of some of the mediators and a more precise delineation of their pathophysiological role. PMID- 7777726 TI - Hypertension induced by drugs and other substances. AB - The purpose of this article is to review and summarize the literature regarding the effects of medications and other substances on blood pressure. Many substances are known to cause or exacerbate hypertension, including sodium chloride, substances of abuse, nonprescription sympathomimetics, nonsteroidal anti-inflammatory drugs, sex steroids, immunosuppressive therapies, erythopoietin, antidepressants, ergot alkaloids, anesthetic agents, and other substances. With the population aging, the increasing incidence of polypharmacy, and the growth of over-the-counter pharmacological agents, including those which were previously available only by prescription, drug-induced hypertension is assuming heightened importance. Furthermore, these agents represent an important modifiable cause of secondary hypertension, and it is imperative that clinicians recognize this causal relationship. PMID- 7777727 TI - Coarctation of the aorta. AB - Coarctation of the aorta is an important and treatable cause of secondary hypertension. The prevalence of aortic coarctation varies from 5% to 8% of all congenital heart defects. Neonates and infants, especially when they have other associated cardiac defects, may present with signs and symptoms of heart failure. Children beyond infancy are usually asymptomatic and are most often diagnosed because of a murmur or hypertension on a routine examination. Palpation of the brachial and femoral pulses simultaneously will show decreased and delayed or absent femoral pulses. On measurement of blood pressure from arms and legs, a pressure difference of more than 20 mm Hg in favor of the arms may be considered as evidence for coarctation of the aorta. The coarctation can be demonstrated on suprasternal notch two-dimensional echocardiographic views along with increased Doppler flow velocity across the coarctation site. Cardiac catheterization shows significant peak-to-peak systolic pressure gradient across the coarcted segment, and aortography demonstrates the degree and nature of the aortic narrowing. Aortic coarctation may be relieved by surgery or by balloon angioplasty; in asymptomatic patients, therapy during the ages of 2 and 5 years is suggested. Surgical relief of coarctation may be achieved by resection and end-to-end anastomosis or by subclavian flap or prosthetic path angioplasty. Although results of surgery are generally good, there are some problems with the procedure, namely, mortality, morbidity and recoarctation, particularly in neonates and young infants and development of aneurysm, paraplegia, and paradoxical hypertension. Balloon angioplasty has been used by some cardiologists with resultant relief of obstruction, but concern for development of aneurysms and arterial complications remain. Although the immediate results for surgical or balloon therapy for isolated coarctation are good, long-term prognosis is largely undetermined. Limited long-term follow-up studies suggest significantly lower survival rates compared with normal population; age at intervention and the degree and duration of hypertension before intervention may affect long-term survival. PMID- 7777728 TI - Evidence based practice. PMID- 7777729 TI - Compliance, clinical effects, and factors predicting weight reduction during a very low calorie diet regime. AB - OBJECTIVE: To study compliance, clinical effects, and factors predicting weight reduction in obese patients treated with a very low calorie diet (VLCD) regime. SETTING: A general practice in Oslo, Norway. SUBJECTS: 253 obese volunteers, aged 15-72, with a mean body mass index (BMI) of 33.4 (25-51) kg/m2. DESIGN: Open, non comparative trial. Patients used a VLCD for eight consecutive weeks to achieve weight loss. The following were recorded every second week: weight, blood pressure, anthropometric measurements, compliance, side-effects, and patient acceptability. Blood parameters were tested before and after the trial. RESULTS: VAS-measurements showed that patients found it easy to comply with treatment, and 87.0% completed the study. Mean weight loss was 13.2 (2-33) kg. Blood pressure, serum lipids, and anthropometric measurements were significantly reduced. Side effects were few and occurred mainly during the first two weeks of the trial. Main factors predicting weight reduction were gender, initial weight, initial BMI, and age. There was no correlation between weight loss and duration of obesity or reported number of weight reduction attempts. By VAS-measurements good acceptability of satiety and taste was recorded, and patients reported improved physical fitness and better quality of life after weight reduction. PMID- 7777730 TI - Current health as a general health indicator. II: Evaluation of reliability and validity. AB - OBJECTIVE: To examine whether a Current Health scale produces reliable and valid measures of self perceived health status. DESIGN: Examination of reliability, based on internal consistency (Cronbach's alpha coefficient). Examination of validity focusing on convergent and discriminant validity. SUBJECTS: 2263 male and female heads of households who participated in The Danish Health Study 1982 83. The survey used items pertaining to health status from Rand's Health Insurance Study. RESULTS: The scale has acceptable properties and is preferable to a single item measure of general health status. It can be used in general practice. PMID- 7777731 TI - Characteristics of attenders and non-attenders at health examinations for ischaemic heart disease in general practice. AB - OBJECTIVE: To clarify the importance of health beliefs and some socio-demographic data for accepting an invitation to take part in a health examination by comparing attenders and non-attenders with respect to health beliefs and social status. DESIGN: Multipractice study including questionnaires for men. SETTINGS: 65 GPs in two areas in the county of Aarhus, Denmark, invited 2452 40-49 year old men to a health examination for ischaemic heart disease. The examination was free in one area, whereas there was a fee in the other. All 1272 attenders and 423/1180 non-attenders completed the questionnaire. RESULTS: The attendance rate was 66% in the area with free examination and 37% in the fee-paying area. The attendance was significantly higher for cohabitants than for single men in both areas. There was a slightly higher attendance of men with an occupational training in both areas, but the difference was not significant. In general, all agreed that IHD is a serious disease, and that it can be prevented by a personal effort. There were only minor differences in the attenders' and non-attenders' health beliefs. CONCLUSION: The main conclusion is that 40-49 year old men are in general concerned about IHD. Whether they want to have a health examination for IHD depends mainly on its availability (exemplified here as fee versus free), since the differences were small with respect to health beliefs between attenders and non-attenders. PMID- 7777732 TI - To prescribe--or not to prescribe--antibiotics. District physicians' habits vary greatly, and are difficult to change. AB - OBJECTIVE: To study how different doctors at a primary health care centre prescribe antibiotics for respiratory tract infections, and, if possible, to identify reasons for differences in prescribing habits. DESIGN: All medical visits to the health centre because of respiratory tract infections during January and February were studied in four consecutive years (1990-1993). The principles for prescribing antibiotics were discussed continuously to obtain more uniform routines. SETTING: The health centre of Teleborg serves a suburban district with about 10,000 inhabitants, and rural surroundings with another 2,000 inhabitants. SUBJECTS: All 2150 visits because of respiratory tract infections (except acute otitis media) made during the studied eight months. All physicians employed at the health centre (five physicians were employed for the whole study period). MAIN OUTCOME MEASURES: Percentage of visits resulting in prescription of antibiotics, and diagnoses given. RESULTS: Antibiotics were prescribed for 76% of the patients by the most generous doctor, but only for 21% by the most restrictive one. The use of diagnoses suggesting bacterial infection varied in a similar way. Otherwise, the patients of the various doctors looked very much the same, and the return visits for the same complaint during the study months were about 5% for all doctors. In spite of the on-going policy discussions, the doctors kept their positions as generous or restrictive prescribers throughout the study period. CONCLUSION: Doctors have an individual and very constant pattern of prescribing antibiotics, and it seems that the diagnoses are often given to justify the treatment, rather than the other way round. PMID- 7777733 TI - Are frequent attenders of primary health care distressed? AB - OBJECTIVE: To measure the level of distress among frequent attenders of primary health care. DESIGN: A cross-sectional study. SETTING: Two public primary health care stations in Turku, south-western Finland PARTICIPANTS: 96 frequent attenders (eleven or more visits to a physician during the previous 12 months) and 466 control patients. MAIN OUTCOME MEASURE: SCL-25, GP evaluations, self-reported symptoms and self-experienced need for care. RESULTS: Frequent attenders were significantly more distressed than other patients in primary care. However, their self-experienced need for psychiatric care was very low and it did not differ from other patients self-experienced need. The GPs estimated that over 1/3 of frequent attenders suffered from mixed (physical and psychiatric) illnesses and over 1/2 from subclinical or clinical psychiatric symptoms. The corresponding proportions for other patients were significantly lower. PMID- 7777734 TI - Measurement of C-reactive protein and the erythrocyte sedimentation rate in general practice. AB - OBJECTIVE: To evaluate the NycoCard:::CRP test (Nycomed A/S, Oslo, Norway) in relation to ESR in consecutive patients in general practice. NycoCard:::CRP test was also compared with a reference method for CRP quantitation. DESIGN: C reactive protein and ESR were simultaneously measured in 607 consecutive patients at four community health centres. SETTING: Four community health centres in southern Sweden. RESULTS: We obtained consistent results in 71% of the cases. In 20% CRP was increased more than ESR, while ESR was increased more than CRP in 9%. CRP was increased in 16% while ESR was below the upper reference limit for age and sex. On the other hand ESR was increased while CRP was below 10 mg/l in five % of the patients. In most of the cases where there was a discrepancy- for example, in infectious diseases-the CRP results were more clear-cut. Using the NycoCard test the CRP concentration can be measured directly in a whole blood sample with the result available within minutes. Comparison of the NycoCard:::CRP test with the reference method for CRP quantitation showed good agreement. CONCLUSION: In clinical situations with suspected inflammatory diseases, the CRP test appears often to yield more useful results than the ESR. The NycoCard:::CRP test is suitable for use in general practice. PMID- 7777735 TI - Do out-of-office laboratory tests affect diagnoses in general practice? AB - OBJECTIVE: To find out whether the GP diagnosis changed by out-of-office laboratory test results and whether his diagnosis became more certain. DESIGN: Descriptive study. SETTING: Dutch survey of morbidity and interventions in general practice: stratified random sample of 161 GPs with a total list of 335,000 patients. SUBJECTS: 2,081 episodes of illness with at least one consultation with clinical chemistry, haematology, or serology tests and at least one follow-up consultation. MAIN OUTCOME MEASUREMENTS: Change in ICPC component or chapter between the consultation in which a laboratory test was ordered and the follow up contact; change in exact ICPC code in cases with important diseases (infectious diseases, haematological disorders, endocrine abnormalities, auto immune processes and malignancies (n = 330)); change in certainty of a diagnosis and change in somatic/psychosocial orientation. RESULTS: After laboratory tests done in the first consultation the ICPC component changed in 46% of the diagnoses. Of the diagnoses made in first consultations without laboratory tests 41% changed in the follow up consultation. The diagnosis after laboratory tests was the same as before in 51% of the consultations with important diseases. Certainty about a diagnosis increased significantly after laboratory tests (p < 0.001). An abnormal laboratory result did not affect the clinical certainty of the general practitioner or the percentage of altered diagnoses. CONCLUSION: The usefulness of tests should be assessed not only in terms of the number of diagnoses changed or of the percentage of abnormal results, but also in terms of the changed certainty concerning a diagnosis. PMID- 7777736 TI - Physical examinations and laboratory tests in antenatal care visits in Denmark. Do reported practice and current official guidelines concord with results of literature reviews? A nationwide study of the public scheme of shared antenatal care in general practice, centres of midwifery and hospital outpatients' clinics. AB - OBJECTIVE: To analyse physical examinations and laboratory tests reported in antenatal care visits in relation to official guidelines and reviews of appropriateness. DESIGN: A nationwide cross sectional study based on questionnaires completed by general practitioners (GPs), midwives, and hospital doctors. Physical examinations and laboratory tests in connection with one specific visit were reported. SUBJECTS: The questionnaires were completed by 722 GPs (61% of eligible from a random sample), 584 midwives (86% of eligible), 250 hospital doctors who made health examinations in pregnancy, week 16-18 (63% of eligible), and 181 hospital doctors who saw women with at-risk pregnancies (55% of eligible). RESULTS: General practice: weight, blood pressure (BP) measurement, and test for proteinuria were reported in more than 90% of visits. Urine culture was reported in 46%, and cervical smear in 41% of first visits. Rubella antibody test at the first visit was only reported in 23% of nulliparae. Vaginal examination was reported in 95% of first visits. Fewer were reported in second (27%) and third (48%) routine visits during pregnancy. Midwives: checks of BP, oedema, and proteinuria were reported in more than 95% of visits irrespective of week of gestation. Vaginal examination was reported in about a third of checkups. Hospitals: vaginal examination was reported in 66% of checkups in at-risk pregnancies. CONCLUSIONS: A surplus of resources were spent on (repeat) examinations and tests with little or no documented benefit. Cervical cytology was grossly overused. Urine culture and rubella serology were not sufficiently applied. PMID- 7777737 TI - Patients' stories: science, clinical facts or fairy tales? AB - OBJECTIVE: To explore potentials and attributes of the qualitative research interview as a tool for acquiring knowledge about illness. DESIGN: A qualitative approach, comparing knowledge about consultations originating from 1) data from interviews with immigrant female patients, and 2) evaluative data from registration forms from the doctors. SETTING AND SUBJECTS: 24 Pakistani female patients, recruited from the appointment list at a primary health care centre in central Oslo were interviewed in their homes. Evaluation forms were filled in by the ten physicians consulted. MAIN OUTCOME MEASURES: Illness knowledge derived from different communicative contexts. Contextual prerequisites suggest potential roads to the inquiry of illness applicable in the clinical context. CASE STORIES: Patients' illness perspectives and resources were probably encouraged in the interview by means of discourse underlining the women's resources. This position may have emerged because the women were actually consulted by the interviewer. Dialogues actively seeking out the other person's illness perspective, as recommended in the qualitative interview, seem to encourage adequate exchange of medical information. CONCLUSION/IMPLICATIONS: Pursuing and modifying strategies from the qualitative interview for exploration of illness may contribute to clinical facts as well as scientific knowledge concerning illness. PMID- 7777738 TI - Day-of-the-week effect on doctors' response to a postal questionnaire. AB - OBJECTIVE: To test a possible day-of-the-week effect on doctors' response rate to a postal questionnaire. DESIGN: Dispatch of postal questionnaire randomized to Thursday or Saturday. SETTING: A nationwide survey on doctors' attitudes. SUBJECTS: 200 general practitioners and 260 practising specialists/consultants. MAIN OUTCOME MEASURES: Response rate and Kaplan-Meier survival curve for no response. RESULTS: The probability of response was not influenced by receiving the questionnaire just before or just after a week-end. CONCLUSION: Response rates in postal surveys sent to doctors cannot be improved by their receiving the questionnaire just before a week-end. PMID- 7777740 TI - The public view on cardiovascular risk factors and changes in lifestyle. AB - OBJECTIVE: To investigate the public knowledge of cardiovascular risk factors including hyperlipidaemia, and attitudes to changes in lifestyle and to the role of the primary health care in preventive work. DESIGN: Postal questionnaire. SETTING: A physically defined area in south-western Stockholm. SUBJECTS: 1000 randomly selected individuals of both sexes 40 to 64 years, stratified into 5 year groups. MAIN OUTCOME MEASURES: Knowledge of and attitudes to cardiovascular risk factors. Contact with the primary health care and expectancy of physicians' interest in patients' lifestyles. RESULTS: Response rate was 75%. The awareness of cardiovascular risk factors was high, but only 51% knew what constitutes healthy food, and two thirds doubted that they could change their eating habits. Forty-eight percent had visited the primary health care during the previous year. Eighty-four percent thought that the physicians should know about their patients' smoking, 83% about drinking habits, and 75% about eating habits. Physicians were expected to spend 40% of their time on preventive work. Only 26% believed that press information about hyperlipidaemia and heart disease did more good than harm. CONCLUSION: Knowledge was good about causative cardiovascular risk factors, but poor about healthy eating. Physicians were expected to have an interest in patients' lifestyle and in prevention. This type of knowledge is important for preventive work. PMID- 7777739 TI - Meeting cancer patients. Interviews with Swedish district nurses. AB - OBJECTIVE: To illuminate district nurses' experiences in the home care of cancer patients. DESIGN: A qualitative approach. SETTING: Primary health care in the south-east of Sweden. PARTICIPANTS: 39 district nurses employed in the eastern part of the county council area. MAIN OUTCOME MEASURE: Interpretation of tape recorded interviews concerning positive and negative experiences of caring for cancer patients. FINDINGS: In the meeting with cancer patients nurses reported some satisfaction, but mainly dissatisfaction and strong feelings of mental strain. Situations identified as especially trying were connected with dressing of ulcerous cancer wounds, managing physical pain, being too close to the patient, not being allowed to communicate openly, not being allowed to help, and patient's trust in alternative medicine. Positive experiences were described when nurses were accepted as helpers. District nurses felt like cowards, and also experienced meaninglessness, uncertainty, shame, irresolution, and insufficiency in the trying situations. The overall emotional tone in the interviews was, however, positive. The deep human contacts were described as a source of both strain and enrichment. CONCLUSION: It seems important to develop support systems to provide district nurses with an opportunity to discuss and handle emotions evoked in the care, thereby improving their possibilities of caring for terminally ill cancer patients. PMID- 7777741 TI - Acute bronchitis: course of symptoms and restrictions in patients' daily activities. AB - OBJECTIVE: To obtain information on the course of complaints and restrictions in daily activities of patients with acute bronchitis. DESIGN: Prospective study. SETTING: General practice. SUBJECTS: Otherwise healthy persons over 16, who visited their GP with an acute cough with purulent sputum and/or auscultatory abnormalities. MAIN OUTCOME MEASUREMENTS: Recordings by patients on reasons for encounter, symptoms and restrictions in daily activities at entry, and one and two weeks after entry. RESULTS: 99 Patients were included, of whom 79 were suitable for further analysis. Discomfort caused by coughing and concern in the patient and his/her social environment were the main reasons why patients visited their general practitioner. Counting from the onset of the disease it took three to four weeks before most patients were well and able to perform all their usual daily activities again. CONCLUSION: In most cases acute bronchitis has considerable impact on patients' well-being and daily activities for some weeks. PMID- 7777742 TI - Adult uncertainty in illness: a critical review of research. AB - Nursing interest in the uncertainty associated with life-threatening illnesses and their treatment technology is growing. Nurse investigators have begun to study variables that precede and influence this uncertainty, as well as how persons appraise, cope with, and adapt to uncertainty. This paper reviews and examines data from both quantitative and qualitative nursing studies of adult illness-related uncertainty published after 1980. Findings demonstrate that uncertainty is a pervasive stressful accompaniment of illness and its treatment that influences persons' coping and adaptive responses. Implications for nursing practice and future research are explored. PMID- 7777743 TI - Health-promoting behaviors and quality of life among individuals with multiple sclerosis. AB - Chronic conditions have profound and pervasive effects on the quality of life of millions of Americans (USDHHS, 1991). The estimated one-quarter million Americans with MS face a unique set of stressors and challenges as they seek to adapt to a chronic illness with an unknown cause, few medical therapies, and an uncertain prognosis that almost always includes some degree of functional disability (Wasserman, 1988). The purpose of this study was to explore factors related to performance of health-promoting behaviors and to examine the relationship between the practice of health-promoting behaviors and perceived quality of life for individuals with MS. A general conceptual model was used as a framework for exploring the relationships among antecedent variables (demographic/disease factors, barriers, resources, perceptual factors), health-promoting behaviors, and perceived quality of life with a convenience sample of 61 individuals with MS. Analyses supported a hypothesized relationship between health-promoting behaviors and quality of life. Subsequent research with larger samples is needed to clearly address the relative strength and path of variables in the proposed model. PMID- 7777744 TI - An analysis of some dimensions of the concept of moral sensing exemplified in psychiatric care. AB - There are few studies that focus on the interpersonal aspect of everyday ethical conflicts. Conceptual frameworks for research into ethical decision making in the health care system are mainly based on an ethic in which objectivity and principle-based thinking is emphasized, leaving the experience of concrete moral conflicts relatively unexplored. The aim of this paper is to analyze the dimensions of "moral sensing," a concept identified in an earlier grounded theory study of psychiatric nursing. Four dimensions of the concept of moral sensing, i.e., feeling, intuition, benevolence and genuineness, were synthesized by reviewing the works of past and contemporary philosophers. The analysis of moral sensing and its dimensions is exemplified by actual nurse-patient encounters in psychiatric nursing practice. PMID- 7777745 TI - In-home communication intervention training for parents of multiply handicapped children. AB - Two major questions derived from social-interactional theory were addressed: What are the effects of an in-home communication training program for parents on (1) the acquisition of child-training skills (imitating/animating and expectant waiting) by parents of developmentally delayed children who have severe language impairments and autistic features and (2) the acquisition of communication behaviors in the children themselves? Questions regarding the social value of the intervention and effects on parent-child interactions were also addressed. Four mothers were taught two parent-training skills (imitating/animating and expectant waiting) during two in-home training sessions. Following the parent training, the mothers conducted training sessions in their homes with their children for 10 minutes, three times per week for 8-12 weeks. All sessions were videotaped and frequency counts taken of the target parent skills and child target behaviors. A single subject experimental research design was used incorporating a multiple baseline across two parental child-training skills (i.e., imitating/animating, expectant waiting). Data were analyzed visually as is customary in single subject experimentation, and direct behavioral counts showed that all four mothers demonstrated increases in the frequency with which they used the child-training skills following treatment. Increases in four child behavior frequencies (i.e., vocal utterances, social responding, social initiating, and intelligible words spoken) were also noted. The ECO Scales Interaction Profile results supported direct behavioral count data, showing significantly improved parent-child interactions for the subject dyads over three conditions (p < .034). Additionally, Parental Consumer Satisfaction Questionnaire results indicated that the intervention was positively perceived by the parents. Furthermore, the utility of single subject experimentation procedures in clinical nursing practice was clearly demonstrated in this research, and the findings support nurse conducted, in-home parent training as a practical and socially valid means of addressing the complex needs of chronically disabled children and their families. PMID- 7777746 TI - Clarity in the caring sciences. PMID- 7777747 TI - Acceptance of ostomy surgery--a Swedish pilot study. AB - The main purpose of this pilot study was instrument development, focused on personal adjustment following ostomy surgery. Two instruments were used: a translated and revised version of the Acceptance of Disability Scale, Modified (ADM), and Antonovsky's Sense of Coherence (SOC) questionnaire. A sample of 26 patients enrolled consecutively at the Ostomy Care Centre at a Swedish hospital were included in the study. A Cronbach's coefficient alpha of 0.95 was obtained for the ADM Scale, Swedish version, which is consistent with the results of similar studies. A significant difference between the ADM scores and type of ostomy surgery indicated that persons with a continent ostomy had a greater acceptance of ostomy surgery than had subjects with conventional ostomy surgery. A close correlation between ADM and SOC was obtained, indicating that persons who accept ostomy surgery will also have a good sense of coherence. The result of this pilot study indicates that further research using both measures may be useful in order to identify which factors are of relevance for nursing practice. PMID- 7777748 TI - District nurses' stories of difficult care episodes narrated during systematic clinical supervision sessions. AB - In systematic clinical supervision sessions 23 Swedish district nurses narrated 147 difficult care situations. The aim of the study was to illuminate their lived experiences of those situations. The following themes emerged in the analysis of the stories: coming too close to the patient; keeping and restoring patient's hope; conflicting opinions; feeling powerless; meeting unrealistic demands; patients' trust in alternative medicine; feeling disgust, shame and guilt; relations to patients' families; and communication gaps. The findings strongly emphasize that district nurses experienced problems in the home care of seriously ill patients. They must not only serve as containers for patients' emotional strain, but they also have to support relatives in their anxiety. However, findings also showed that there was often a balance between negative and positive dimensions in these meetings with dying patients and their families. It seems important to form support groups to help district nurses deal with demanding care situations and to relieve them of feelings and thoughts aroused in the provision of care. Support in the form of clinical supervision may impact the quality of care in a positive way. PMID- 7777750 TI - Some aspects of colour perception among patients with Alzheimer's disease. AB - The proportion of elderly people in western societies is on the increase. At the same time, demands are being heard for improvements in the quality of health care, including the design of the physical environment. The aim of this study was to call attention to some aspects of colour and the possibilities of using it as an orientational aid for institutionalized demented patients and thereby enhance the quality of their care. A pilot study was carried out to establish whether patients with Alzheimer's disease are different from non-demented patients regarding certain aspects of colour perception. Twelve hospitalized patients with Alzheimer's disease were compared with a matched control group of non-demented patients regarding colour naming, colour discrimination and colour preference. No significant differences were found between the groups. In an additional experiment to test short-term memory it was found that the patients with Alzheimer's disease gained substantial help from colour cues. It is concluded that colour should be taken into account in the designing of the health care environment, particularly geriatric wards. PMID- 7777749 TI - The trustworthiness of the stories of elder abuse narrated by district nurses. AB - The aim of the present study was to assess the trustworthiness of previously reported stories about elder abuse narrated by 21 district nurses (DNs) regarded as witnesses. Firstly, the stories were coded as to whether they were based on direct observation, hearsay or a mixture, and whether there were whole stories or story fragments. Secondly, they were coded and classified regarding a modification of the characteristics of reality developed from statement reality analysis. The DNs' single stories matched most of the characteristics. The results indicate that the DNs' stories are a reliable account of a personally experienced real event. Witnesses' stories are important sources in revealing phenomena, such as elder abuse. It also seems important to develop usable methods further. PMID- 7777751 TI - Activities of daily living ratings of elderly people using Katz' ADL Index and the GBS-M scale. AB - Instruments for measuring activities of daily living (ADL) are useful in estimating institutionalized elderly ill people's need of care. The aim of the present study was to investigate to what extent the GBS-M scale measures ADL status, as determined by Katz' ADL Index. Forty-two elderly patients in long-term care in a psychiatric hospital were rated independently using each of the two scales. The correlation coefficient between results of the ratings was r = 0.93, i.e., high scores on one of the scales gave high scores on the other scale. Fifty per cent of severely demented patients had maximal scores on measures of ADL. PMID- 7777752 TI - The helping encounter--occupational therapists' perception of therapeutic relationships. AB - The present paper deals with the art of occupational therapy in terms of therapeutic, helping relationships. The aim was to get a picture of how occupational therapists perceive the therapeutic encounter with their patients. Sixteen qualified occupational therapists, from various occupational areas, were interviewed and a qualitative approach was employed to analyze their description of therapeutic encounters in clinical settings. The qualitative analyses were performed with sensitization as the principle objective and a tentative theoretical model was formed, developed by three content categories; 1) Basic Professional-Oriented Helping; 2) Understanding-Oriented Helping; and 3) Action Oriented Helping. The relationships between these categories constitute a dynamic complex pattern. One conclusion drawn from this model was that the therapists might have problems finding a balance between their aspiration for becoming professionalized and their belief in egalitarian patient-therapist relationships in the rehabilitation treatment sessions. PMID- 7777754 TI - [The hypoxic patient. Introduction]. PMID- 7777753 TI - Improvement after surgery in patients with osteoarthrosis of the knee. AB - To ascertain both physical and psychosocial effects of knee surgery in patients with moderate gonarthrosis, clinical examination of patients has been supplemented with a questionnaire SIP (Sickness Impact Profile) to describe the functional health status. Sixty patients, 35 women and 25 men, mean age 63 years, with moderate medial osteoarthrosis of the knee were included in the study. Sixteen patients had bilateral symptoms of gonarthrosis. Patients considered that their knee ostheoarthrosis had great influence physically as well as psychosocially. All patients graded pain during walking. Thirty-five patients were treated with a medial unicompartmental knee endoprosthesis and 25 patients were treated with a valgus osteotomy. After surgery the mean values for all measured variables were improved. Superior results were found among patients with unilateral disease compared to patients with bilateral disease. No differences in results were found between patients given different surgical treatments. The physical and psychosocial influence of osteoarthrosis of the knee were more pronounced in women. It is concluded that the SIP appears to be a measure with sufficient sensitivity to detect physical and psychosocial changes in patients with moderate osteoarthrosis of the knee. PMID- 7777755 TI - [Diurnal and nocturnal hypoxia]. PMID- 7777756 TI - [Adaptation to chronic hypoxia]. PMID- 7777758 TI - [Continuous home oxygen therapy: benefits, indications, methods]. PMID- 7777757 TI - [The traveling patient with hypoxia]. PMID- 7777759 TI - [Monitoring of continuous home oxygen therapy]. PMID- 7777760 TI - [Exertional hypoxia and portable oxygen therapy]. PMID- 7777761 TI - [Uronephrological and urogenital tumors: the urologist's viewpoint]. PMID- 7777762 TI - [Cancer of the kidney]. PMID- 7777763 TI - [Superficial bladder tumors. Pathological and clinical review and presentation of a new diagnostic method: fluorescence photodetection of transitional epithelial carcinomas based on protoporphyrin IX induction with delta-aminolevulinic acid (5 ALA)]. PMID- 7777764 TI - [Spontaneous development and treatment of localized cancer of the prostate]. PMID- 7777765 TI - [Metastatic cancer of the prostate: course, diagnosis and therapeutic management]. PMID- 7777766 TI - [Efficacy of Rhinomer Force 3 in the postoperative course of endonasal surgery]. PMID- 7777767 TI - [Ultrasonic lipolysis. Liposculpture with ultrasound]. PMID- 7777768 TI - [Andropause, male climacteric and crisis of the fifties: should androgens be administered?]. PMID- 7777769 TI - [Discussion apropos of a case of ulcerative colitis]. PMID- 7777770 TI - [Certificate of continuous education in public health: a Swiss first at the University of Geneva]. PMID- 7777771 TI - [Which psychotherapy by which physician?]. PMID- 7777772 TI - [Homage to a grand lady]. PMID- 7777773 TI - [The content of nitrates and nitrites in fruits, vegetables and other foodstuffs]. AB - There are presented the results of the investigation of many popular fresh and frozen vegetables as well as in fresh and frozen fruits, such as different kind of apples, strawberries, currants, raspberries and many other tender fruits mainly from market and few from own allotment-cottages performed in the year 1989 1992. The nitrate and nitrite was determined according to the Griess reaction. High levels of nitrate was encountered in lettuce, frozen spinach, fennel, radishes, parsley. Many of this samples contained more than 1000 mg of KNO3/kg of fresh product, but the highest level, over the 3500 mg/kg was found in lettuce. The remaining vegetables like carrots, celery, leeks and frozen French bean contained from several dozen to more than 800 mg KNO3/kg. The level of nitrite in all samples of the investigated vegetables and fruits was very low from zero to decimal part of milligram per kg. Very low level of nitrate was found in 7 species of investigated apples (from 1.3 to 9.7 mg KNO3/kg). A little higher level of this compound was ascertained in currants, gooseberries, raspberries, cherries (from 0.0 to 36.0 mg KNO3/kg product). The highest levels of nitrate occurred in samples of strawberries (maximum to 322.3 mg KNO3/kg) but mean level amounted 58.7 mg KNO3/kg. The encountered levels of nitrate in frozen vegetables and fruits as well as in jams and stewed fruits was only little less than in fresh products. Very high level (from 355.30 to 584.53 mg KNO3/kg) was ascertained in the fruit-vegetable juice named "Rinberen" and "Malberen" to which red beet extract was used for their production. It should be pointed out that when the containers of these juice was opened and stored at the room temperature (+20 degrees C) during 30 days, no changes was observed in the level of nitrate and nitrite. In the juice prepared from blanched carrot, the rate of the reduction of nitrate to nitrite has not been lowered, when this product was storage of this juice at room temperature, the mean level of nitrite increased significantly (from 0.14 to 82.89 mg NaNO2/kg) and the level of nitrate lowered from 261.0 to 46.4 mg KNO3/kg. It should be strongly recommended for consumption the juices from carrot only fresh prepared. There are also presented the results of investigation of nitrate in fermented cheeses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7777774 TI - [Occurrence of aluminum in some foodstuffs]. AB - Results of aluminium determinations in breads and biscuits as well as in fish preserves, vegetables, strawberries and teas including fruit-herb teas are presented. Also the percent of extraction of aluminium of various kind of tea leaves into the infusions was determined. The commercially available sample of foods was used for investigation. Aluminium was determined by using two methods: a spectrophotometric extraction method with-hydroxyquinoline and less sensitive AAS method with nitrous oxide-acethylene flame on PU 9100X Philips Spectrometer could with IBM compatible Computer (Hundai) provided with 9178/9X Flame Program Unicam Limited--1991. The sample was at first digested with mixture of concentrated acids (H2SO4 + HNO3 + HClO4) in teflon vessels and then finished in platinum dishes. Solutions of the destroyed samples was kept in polethylene bottles. The methods was checked by recovery tests. In the 8-hydroxyguinoline extraction-method about 88.5% to 106.5% of the added aluminium was determined and in the AAS method it was of 75% to 100%. The highest level of aluminium was found in the eas: from 445 to 1522 mg/kg (mean 879 mg/kg) and then in herb-fruit teas (consisting of dried herbs and fruits of sloe plum, briar-rose juneberry Aronia etc.) from 45 to 379 mg Al/kg of dry matter. About 29% of the metal was extracted from teas into the infusion. Lower levels was found in breads (0.0-92.0 mg mean 29.95 mg/kg) and in the fish preserves (0.0-57.0 mg mean 18.1 mg AL/kg). Similar levels were also found in 7 kinds of popular vegetables (0.0-100 mg mean 33.3 mg Al/kg). The lowest levels was found in strawberries (0.50-3.0 mg Al/kg). It was calculated that drinking three glasses of tea daily may supply about 2.6 to 3.7% of the provisional tolerable weekly intake dose set by the Joint FAO/WHO Expert Committee. It is concluded that the obtained results are similar to those published by other authors and represents a levels normally encountered in foods, and do not create any risk for human consumption. PMID- 7777775 TI - [Comparative analysis of certain nutritional parameters of fat in food rations of various population groups. II. Composition of fatty acids]. AB - Daily food rations showed a high content of saturated fatty acids, especially in males and females employed in white collar work. The content of monounsaturated acids was lower, and the per cent of energy from these acids complied with the present nutritional suggestions. The per cent of energy from polyunsaturated acids was below these suggestions. The studied food rations contained high amounts of fatty acids with properties favouring hyper-cholesterolaemia and platelet aggregation, while those causing hypocholesterolemia (unsaturated acids) were present in insufficient amounts. This was noted particularly in the food rations of working people and retired workers. The variance analysis showed statistical. Significance of the differences between the mean values of the studied parameters of fats of various population groups. PMID- 7777776 TI - [Comparative analysis of certain nutritional parameters of fat in food rations of various population groups. III. Use of correlation and regression analysis for assessment of the nutritional quality of fat]. AB - Correlation and regression analysis demonstrated a high degree of correlation between saturated and monounsaturated fats, on the one hand, and the absolute fat content, and lower correlation with polyunsaturated fats. The increase of fat content raised the saturated fat content in the daily food rations of mental and physical workers with the lowest rise of polyunsaturated fatty acids. The rise of the per cent share of saturated fatty acids was always at the expense of monosaturated fatty acids whose content decreased. A similar change was observed in polyunsaturated fatty acids. From the standpoint of nutrition another unfavourable finding was the demonstrated negative correlation between monosaturated and polyunsaturated fatty acids. PMID- 7777777 TI - [Codex foodstuffs committee FAO/WHO on methods of analysis and sampling]. AB - The topics of the XIX Session of the Codex Alimentarius Committee held in Budapest are reviewed. In the report on the Session the main stress was laid on the matters connected with guidelines on sampling, endorsement of methods of analysis for codex standards and the matters concerning quality assurance systems in laboratories. PMID- 7777778 TI - [Formaldehyde determination using the colorimetric method with acetylacetone. II. Formaldehyde determination in cosmetic emulsions and certain household products]. AB - Total formaldehyde content was determined by the colorimetric method with acetylacetone in cosmetic emulsions and household products. The commercial products not containing formaldehyde were fortified with 150 micrograms of the investigated compound. Recovery in this method was 93.3-102.6%. The method was found useful in routine determinations of formaldehyde in cosmetics and household products and can be used by the State Sanitary Inspections. PMID- 7777779 TI - [Formaldehyde determination in packing paper for food products by the colorimetric method with acetylacetone]. AB - Papers used for food packing were studied for formaldehyde migration from them by the colorimetric method with acetylacetone. The studied material comprised 14 samples of paper of Polish or foreign production: pergamenous paper, offset and sulphite papers and one sample from waste paper imported from Germany. Formaldehyde migration from these samples differed but never exceeded 1 mg/dm2, with the exception of the recycled paper from which it was 1.77 mg/dm2. PMID- 7777781 TI - [Bacterial age and their susceptibility to disinfectants]. AB - The comparative tests were carried out on 4 standard test microorganisms grown 24 h, 48 h, 72 h, with regard to their susceptibility to 6 disinfectants. The activity of disinfectants was examined by Berry and Bean method--mean single survival time (MSST). The results indicate that 24 h grown bacteria have the lowest susceptibility to phenol, Septyl, formalin, glutaraldehyde, chloramine and Sterinol. The MSST of these short time grown bacteria was 2-3 times longer than that of 72 h grown. PMID- 7777780 TI - [Studies on the chronic toxicity of a mixture of lead, cadmium and iron given to white rats with drinking water]. AB - The experiment was carried out on male white rats of own breed which were receiving for 8 months lead acetate 200 mg/l, cadmium acetate 50 mg/l and ferrous chloride 100 mg/l with drinking water. The experimental groups received lead, cadmium, lead with cadmium, and the last group received every other day alternatingly iron or lead with cadmium. The activity of selected blood enzymes, haematological indices was determined and the memory test was carried out. In all experimental groups a decrease was noted of haemoglobin level and haematocrit value, with an increase of choline esterase and reduced learning effectiveness- most pronounced in the group treated with cadmium, less evident in groups drinking water with lead or cadmium and lead, and not significant in the group receiving iron with lead and cadmium. PMID- 7777782 TI - [The effect of temperature on bactericidal activity of certain disinfectants]. AB - Increase of the temperature by 10 degrees C (on the temperature range 22-32 degrees C) grows up the bactericidal activity of the disinfectants like Laurosept, Chloramine, Sterinol and Jodoseptan against E. coli and S. aureus. It has not observed the influence on the bactericidal activity of Septyl against S. aureus. Surface-active agents are more effective at higher temperature against S. aureus, phenolic disinfectants and Chloramine against E. coli. PMID- 7777784 TI - [Noise in vocational schools. Causes of occurrence and assessment of exposure to schoolchildren]. AB - Acoustic conditions in the classrooms of vocational schools are comparable with those in high schools. However, much worse acoustic conditions are observed in vocational school workshop. The evaluation of acoustic conditions in 712 school shops showed, that noise exposure of schoolchildren is very various and depends upon type of workshop and tasks performed by schoolchildren. The major source of noise exposure is machinery in mechanic workshops (plastic working--up to 105 dB, machine noise-from 80 to 90 dB), in textile workshops--from 90 to 100 dB and woodworking machines-from 92 to 102 dB. It should be noted that in such acoustic conditions schoolchildren stay for a relatively long time. Average exposure time of schoolchildren in mechanic or textile workshops was about 4.5 hours. At another training subjects i.e. electric, building, welding craft or gastronomy- noise exposure is usually below recommended standards (80 dB). The critical values accepted for hearing protection for occupational exposure (85 dB) were exceeded at 10% investigated training places of schoolchildren. This mostly occurred in mechanic workshops. Taking into account increased sensitivity of young people it would be worthwhile to work out separate criteria in this range for school workshops. Tentatively, problem should be solved by shortening exposure time depending on actual noise level. PMID- 7777783 TI - [The stability of biological indicators used for monitoring ethylene oxide gas sterilization]. AB - It was found the correlation between the storage time of biological indicators and their usefulness for monitoring of gas sterilization with ethylene oxide (EO). Bacillus subtilis var niger ATTC 9372 was used as a test organism. Two kinds of investigations were done: observation of bacterial growing or lack of growing after 1 hour exposition of storage tests in EO (EO concentration- 750 mg/l, temperature +/- 50 degrees C, (humidity-40%) and examination of drop in number of spores on strip tests after storage time. The results show that sterilization efficacy may be monitored using such spore strip tests up to six months of storage. PMID- 7777785 TI - [Noise level in Szczecin schools and selected health indicators of students]. AB - There was an examination made in thirty schools chosen at random in Szczecin as for the level of indoor and outdoor noise. In two-thirds of the schools noise was found out to exceed the accepted limit. There was larger number of children with hearing deficiencies and/or psychic disturbances in those schools. The conclusion of the investigation can be drawn that one of the causes of transgression of indoor noise limit in newly built schools is the use of building materials of low insulating power. Additionally green areas should be set up and acoustic screens in order to separate schools in the centre of the city which are exposed to a high level of outdoor noise. PMID- 7777786 TI - [Competence of families for providing sex education of children]. AB - This investigation explores the conditions under which children's sex education in families takes place. In particular, types of parents activities are examined, the parents attitude toward sexual concerns of children is assessed, as well as, moderating social ties are identified. The study population includes 1239 primary school students of the 7th grade, randomly selected from Warsaw primary schools. The findings show insufficient proficiency of families in sex education of their children. Although parents are the most desired source of sex related information, the range of their info-educational activities is found to be limited. This is particularly true when sons are considered; more attention is being paid to daughters. The results also indicates that mothers are more engaged in sex education than fathers. The findings show positive correlation between proficiency of parents in this field and their social status. This competence is also higher in families with better communication between members and families in which child freedom is not essentially limited. PMID- 7777788 TI - 3rd Current Topics in Gastroenterology Symposium. Sandpiper, Florida, October 31 November 2, 1993. Proceedings. PMID- 7777789 TI - Transplantation of isolated hepatocytes and their role in extrahepatic life support systems. AB - Transplantation of isolated hepatocytes for the replacement of liver function and the use of isolated hepatocytes as a bridge-to-transplantation in extrahepatic bioartificial liver support devices offer important therapeutic advances for treating severe liver disease. Progress in cell biology, tissue culture techniques and biotechnology have led the way for the potential therapeutic use of isolated hepatocytes in a wide array of liver disorders. Transplanted hepatocytes show considerable promise of performing the full range of liver functions in several animal models of liver disease, ranging from fulminant hepatic failure to congenital metabolic liver disease. Recently, several interesting designs for extrahepatic liver support systems have been proposed. Although there is no current consensus on its eventual design configuration, the hollow fiber hepatocyte bioreactor design has the greatest potential for therapeutic benefit. PMID- 7777787 TI - [Remembrance of Professor Bruno Nowakowski]. PMID- 7777791 TI - Small bowel transplantation. AB - The small bowel, the largest lymphoid organ in the body and host to a myriad of foreign antigens has presented a formidable challenge for transplantation. In the past 5 years, small bowel transplantation has become a viable clinical entity. Successful transplantation of the small bowel has been achieved as part of multivisceral grafting, combined small bowel and liver grafts and even as isolated small bowel grafts. Allograft rejection remains an important post transplantation problem, although graft versus host disease has been less of a clinical problem than initially feared. Markers that may serve to predict early rejection have been identified and include: assessment of endoscopic biopsies for enterocyte Class II antigen expression and for mucosal T cell and macrophage infiltration, bowel permeability studies, and measurement of changes in transepithelial potential difference. Earlier detection of rejection and more potent therapy for rejection episodes will be necessary to further improve outcomes. PMID- 7777790 TI - Early clinical experience with a hybrid bioartificial liver. AB - BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation. PMID- 7777792 TI - Transplantation of islets of Langerhans in patients with insulin-dependent diabetes mellitus. AB - From 1974 to December, 1992, as reported by the International Islet Transplant Registry, there have been 175 adult islet allografts worldwide. Ninety-eight of these transplants have been performed since 1989. Eleven patients with Type I diabetes mellitus who have received islet allografts since 1989 have achieved insulin-independence for variable periods of time. As of June, 1993, four patients remain insulin-independent (from > 127 to > 326 days). Insulin independence after human islet cell transplantation is not yet a consistent achievement. Several key issues in pancreas procurement, islet cell isolation, islet preservation, islet engraftment and the prevention of islet allograft rejection still need to be addressed. The expansion of current clinical trials should be limited to patients who are taking or who require immunosuppressive drugs for other reasons (kidney or liver transplant recipient) since the risks of chronic immunosuppression probably outweight the risks from chronic diabetes, although as we are able to induce a more specific state of immunosuppression this rationale may become debatable. PMID- 7777793 TI - Aspects of quality of life in gastrointestinal disease: some methodological issues. AB - Quality of Life assessments have many applications in clinical trials. In the evaluation of gastrointestinal disease for example. Quality of Life outcomes provide a useful tool for assessing treatment response. There are a number of standard measures currently available that may be utilized to determine Quality of Life. In clinical trials the use of questionnaires allows the clinician to assess the impact of disease and its subsequent treatment upon the patient's daily life. In order to facilitate comparison of data between studies, it is important that the measures selected are well validated. Patients with gastrointestinal problems do not only experience symptoms. The symptoms have an adverse impact on well-being and ability to enjoy day-to-day activities. It is important to provide appropriate treatment for the large and heterogeneous population with gastrointestinal complaints who have a poor Quality of Life. PMID- 7777794 TI - Quality of Life assessments in the evaluation of gastroesophageal reflux and peptic ulcer disease before, during and after treatment. AB - BACKGROUND: It has recently been suggested that Quality of Life (QOL) be used in the evaluation of new medical treatment regimens together with cost-benefit, efficacy and safety. In this overview we point out some aspects of use of the Psychological General Well-Being Index (PGWB) in patients with peptic ulcer and reflux disease gained from our own investigations in later years. METHODS: QOL was assessed using questionnaires before diagnosis, during medical healing treatment and at a 1-year follow-up in peptic ulcer disease or before and after surgery in reflux disease. RESULTS: Untreated patients with unknown diagnosis had low QOL scores. With treatment, scores increased rapidly to supernormal values and fell off to normal values during the follow-up year. CONCLUSION: QOL evaluations seem sensitive and reflect the patient's subjective feeling of disease. They add another new aspect of treatment effect not earlier included in treatment evaluations. PMID- 7777795 TI - Quality of Life in inflammatory bowel disease: biases and other factors affecting scores. AB - Health-Related Quality of Life (HRQOL) measurement has become a key element in the assessment of chronic diseases during the execution of clinical research and in the delivery of health care. Poor HRQOL is clearly recognized in patients with inflammatory bowel disease (IBD) and relates to the type of disease (Crohn's disease or ulcerative colitis) and disease severity. It is also linked to non disease elements e.g., gender, age, personality, cultural factors and coping skills. The dynamic properties of HRQOL may be depicted using different measurement tools and the portrayal may well differ when using a generic- or a disease-specific instrument. HRQOL status also changes with time, as do disease and non-disease parameters. Several examples of population selection bias are demonstrated using the Sickness Impact Profile (SIP), the time trade-off and the McMaster Inflammatory Bowel Disease Questionnaire (IBDQ). While HRQOL is generally good in IBD patients, mean HRQOL scores are still significantly depressed compared to normal controls. The IBDQ, a disease-specific HRQOL instrument, has yielded consistent results in both cross-sectional studies and prospective clinical trials. Such HRQOL instruments can be used to identify the types of new therapies that are needed, subgroups of patients which might benefit from specific treatments, patient satisfaction, treatment efficacy and efficiency. These applications must always be undertaken with careful attention to rigorous research methodology. PMID- 7777797 TI - Quality of Life: a critical assessment. AB - There is increased recognition that Health-Related Quality of Life (HRQOL) or Health Status (HS) is important and, together with other outcome measures, highly relevant to evaluating both the impact of diseases, and the individual and societal benefits/costs of different interventions, management strategies and health policies: yet many problems remain. While the methodology of HS assessment has been extensively studied and greatly improved, implementation has lagged in practice and in clinical research. Resources have been forthcoming for studies which promise increased profit (e.g., marketing advantage) or cost-containment, but funding has been scarce when the focus is on quality of care, patient utility, or health issues such as screening, monitoring or disease prevention. There are well-defined limitations associated with various assessment instruments, with interpretation of scores, and with the lack of relationship between disease activity and overall HRQOL. For these reasons, to date, HS assessment has not been clearly shown to be useful to physicians or to benefit patient outcomes to a degree sufficient to justify the burden of widespread use. Physicians remain cautious of the processes, especially with those aspects that relate to values, autonomy, equity, legal liability and potential for abuse. PMID- 7777796 TI - Gastric blood flow in ulcer diseases. AB - BACKGROUND: Gastric blood circulation maintains the structure and functions of the stomach, and thereby is closely associated with the pathogenesis and the healing of gastrointestinal lesions. Gastric mucosal blood flow, regulated by systemic neural and humoral factors, is also modified by local metabolic factors such as prostaglandins, leukotrienes. PAF and other endogenous chemical mediators in mucosa. Endothelium-derived factors that are produced by vascular endothelial cells, inducing relaxation or contraction of the blood vessels, are also recognized as basic mediators that regulate the circulation in the stomach. RESULTS: The regionally disturbed gastric circulation in combination with the presence of acid is closely associated with the pathogenesis of NSAIDs and ethanol-induced gastric lesions. Blood flow and oxygenation in the surface mucosa surrounding the peptic ulcer change during healing, depending on the quality of the ulcer healing process: an increased blood circulation with increased oxygen supply to the ulcer margin is important for rapid ulcer healing shown by reflectance spectrophotometry. Factors altering the blood flow during the ulcer healing are discussed. PMID- 7777798 TI - Hepatitis C in 1994. AB - Since the discovery of hepatitis C in 1989 its role in the development of acute and chronic liver disease has been carefully evaluated. Hepatitis C has a mean incubation period of between 6 and 8 weeks. It is often indolent and asymptomatic. Interferon may be helpful in chronically infected patients. After 6 months of therapy approximately 40-50% enter remission. Relapses are common however, up to 80% within 6 months. Effective long-term treatment has not yet been established. PMID- 7777799 TI - Influence of initial therapy on outcome of peptic ulcer. AB - Histamine 2 (H2) receptor antagonists, proton pump inhibitors, prostaglandin analogues, colloidal bismuth and sucralfate have all proved safe and effective in the initial treatment of peptic ulcer. Yet, most ulcers will recur when treatment is stopped. Continuous maintenance with H2 antagonists results in low symptomatic relapse, complications occur rarely, and such treatment is safe. An alternative is Symptomatic Self Care (on-demand therapy), which provides an economic option for patients with no concomitant disease or previous complications. Meta-analyses suggest a higher relapse rate after H2 antagonist therapy than that following sucralfate or bismuth. Whilst improved morphology and/or functional status of the gastro-duodenal mucosa ('quality of healing') has been claimed, the difference has not been explained. Successful prolonged eradication of Helicobacter pylori leads to a very low relapse rate, but more effective, predictable and safer eradication regimens are needed. PMID- 7777800 TI - Mechanisms of mucosal injury and healing: the role of non-steroidal anti inflammatory drugs. AB - Biological insights into injurious effects of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), on mucosal protection and repair, are largely from studies of acute injury. That chronic ulceration is similar is not established. NSAIDs directly injure tissues, including endothelia, and at the same time impair the operation of many of the processes that normally contribute to mucosal protection, whatever the injurious agent. Many protective processes are mediated through prostaglandins, whose synthesis is abolished by inhibition of the constitutive isoenzyme, cyclooxygenase I (COX I) or Prostaglandin H Synthase1 (PGHS1). The aims of therapy are aimed at inhibiting the inducible isozyme cyclooxygenase II (COX II) or prostaglandin-H Synthase2 (PGHS2), which contributes to prostanoid synthesis at sites of inflammation. Newer NSAIDs, selectively inhibiting COX II, promise to revolutionize the treatment of inflammatory disease while reducing mucosal injury. Meanwhile, there is increasing evidence that direct injury to both mucosae and endothelia is mediated by free-radical species, exacerbated by reduced blood flow, and by the local release of inflammatory and other mediators, which accentuate vascular leakage and hemorrhage, and cause intravascular aggregation of blood elements, stasis, hypoxia, and additional free-radical injury. The NSAIDs also inhibit epithelial cell division and the angiogenesis critical to healing and repair. PMID- 7777801 TI - Molecular and cellular basis of ulcer healing. AB - BACKGROUND: The high ulcer recurrence rates after treatment with antacids or antisecretory drugs illustrate the need for direct treatment of GI ulcers by stimulating repair and healing mechanisms. The molecular regulators of ulcer healing include polyamines and growth factors such as EGF, TGF-beta, bFGF and PDGF. METHODS AND RESULTS: Oral treatment of rats with bFGF or PDGF accelerated the healing of chronic cysteamine-induced duodenal ulcers without decreasing gastric secretion. We found that sucralfate binds bFGF in vitro and in vivo, and the elevated local concentration of this growth factor may contribute to the ulcer healing properties of sucralfate. Parallel treatment with bFGF + sucralfate resulted in synergistic healing of chronic duodenal ulcers and chronic gastritis. CONCLUSIONS: Rapid changes in mucosal concentration of bFGF and EGF receptors during ulceration suggest that these peptides play a role in the natural history of GI ulcers. Thus, treatment based on molecular and cellular mechanisms of ulcer healing allows a direct and efficient ulcer therapy. PMID- 7777803 TI - Helicobacter pylori. AB - Helicobacter pylori is an important cause of chronic active gastritis and is strongly associated with peptic ulcer disease and gastric cancer. H. pylori colonizes the surface of the gastric epithelium with production of a number of factors, resulting in inflammation and an altered mucosa. H. pylori infection occurs world-wide and the mode of transmission most likely is from human to human via the fecal-oral and/or the oral-oral route. Treatment and, in the future, prevention of this infection may result in a marked diminution of upper gastrointestinal tract disease. PMID- 7777802 TI - Mucosal immune response to Helicobacter pylori and cytotoxic mechanism. AB - BACKGROUND: Helicobacter pylori is widely accepted as a major pathogen in gastritis. The histologic features of H. pylori gastritis are the numerous infiltrating mononuclear cells (MNCs) and neutrophils. It is not clear what role the infiltrating MNCs and neutrophils play in H. pylori gastritis. METHODS: In this study, we have established enzyme-linked immunospot (ELISPOT) assay for the measurement of H. pylori antibody-producing cells in gastric mucosa. RESULTS: Using ELISPOT assay, we found that H. pylori-specific IgA-producing cells as well as IgG-producing cells were distributed in gastric mucosa. These H. pylori specific antibodies in gastric mucosa and neutrophils are responsible for the induction of cytotoxic effect to cultured Vero cells. CONCLUSIONS: These observations suggest that a mucosal immune response specific to H. pylori is closely associated with the pathogenesis of gastritis. PMID- 7777804 TI - The current role of Helicobacter pylori eradication in clinical practice. AB - Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis. It is increasingly accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 100%. More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those whose ulcers have been healed but in whom the infection persists. There is increasing evidence that what is now clear for duodenal ulcers may also hold true for patients with a gastric ulcer who are infected with H. pylori. Moreover, evidence is accumulating that the risk of a duodenal ulcer complication, such as, bleeding, is reduced following successful eradication of H. pylori. The treatment of duodenal ulcer patients with H. pylori eradication treatment has been advocated by an international working party who met first in Sydney at the 1990 World Congress and subsequently in Athens during the First European Gastroenterology Week. The most recent recommendation suggests that the infection should be treated in any duodenal ulcer patient after the first recurrence, and that a triple therapy regimen or a proton pump inhibitor combined with either amoxicillin or clarithromycin may be prescribed. The combination of a proton pump inhibitor and an antibiotic can eradicate H. pylori in over 80% of cases and simultaneously offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777805 TI - Malnutrition in the developing and developed world: is small intestinal bacterial colonization important? AB - Malnutrition is a major problem on a global basis and will continue if current world population trends persist. Small intestinal bacterial colonization may contribute to malnutrition in populations whose dietary intake is marginal, such as those in developing countries and many elderly in the developed world. This review focuses on the evidence for small intestinal bacterial colonization in these subjects and briefly revises current thinking on the pathogenesis and diagnosis of this condition. PMID- 7777807 TI - Laparoscopy for abdominal emergencies. AB - The role of laparoscopy has been reviewed for these conditions: abdominal trauma, acute abdomen, abdominal pain of uncertain etiology, appendicitis and the acute abdomen in the intensive care unit patient. Laparoscopy should only be performed in trauma patients who are hemodynamically stable and who have some evidence for abdominal injury, such as a positive peritoneal lavage or a positive CT scan. Laparoscopy is an excellent procedure for determining whether a knife or missile has penetrated the peritoneum. For penetrating wounds in the chest and upper abdomen, laparoscopy also allows excellent evaluation of the diaphragm. In blunt trauma, laparoscopy identifies the majority of injuries, but there has been a 5 15% incidence of missed injuries to the small bowel and colon. The acute abdomen is generally caused by perforation, acute inflammation or intestinal obstruction. Of the various types of perforation, diagnostic and therapeutic laparoscopy is most applicable for duodenal perforation. Acute perforation of the stomach and colon should probably be treated by standard open techniques. For acute inflammatory disorders, laparoscopy is an excellent diagnostic tool and can also provide definitive treatment in the form of drainage of an abscess or appendectomy. The role of laparoscopy for ileus and bowel obstruction is controversial; some surgeons advocate diagnostic laparoscopy and treatment, while many others still consider bowel obstruction and abdominal distention to be contra-indications. Finally, there are the intensive care unit patients in whom an acute intraabdominal process is suspected. Laparoscopy in such patients alters the clinical management in about 50% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777808 TI - Totally preperitoneal laparoscopic inguinal herniorrhaphy using balloon distention. AB - BACKGROUND: After having performed over 200 transabdominal preperitoneal (TAPP) laparoscopic hernia repairs with no recurrences and no neuropathies, we recently changed to a totally preperitoneal repair due to the development of a balloon trocar that easily 'creates' the preperitoneal space. METHODS: The totally preperitoneal operation is similar to our TAPP procedure in that it involves detailed delineation of Cooper's ligament, spermatic cord and transversus abdominis arch with fixation of mesh to Cooper's ligament and arch for an anatomic tension-free hernia repair. RESULTS: Our early experience consists of 60 hernia repairs in 50 patients (46 male, 4 female). There were 32 direct, 26 indirect and two femoral hernias. Eight hernias were recurrent. The operation takes approximately 1 h. There has been no morbidity. As with the TAPP procedure, minimal postoperative discomfort and return to regular activity within 2 to 3 days is the norm. CONCLUSIONS: We believe that the avoidance of the peritoneal incision and the attendant risks of intraabdominal adhesions associated with the TAPP procedure make the totally preperitoneal technique the preferred method of laparoscopic hernia repair. PMID- 7777806 TI - Laparoscopic Rosetti fundoplication. AB - BACKGROUND: Early experiences with laparoscopic fundoplication using the Rosetti technique are presented and compared with retrospective results from conventional fundoplication procedures. METHODS AND RESULTS: We have performed 70 consecutive laparoscopic procedures. Conversion to open surgery was done in seven cases because of anatomical reasons and in two because of peroperative progressive subcutaneous emphysema and CO2-retention. The complication rate was low. The range of postoperative hospital stay is 1-4 days for non-converted patients. Symptomatic follow-up has hitherto been performed in 41 patients with a follow-up time of 3-9 months. The follow-up results do not differ from those achieved in patients operated upon with the conventional open Nissen (n = 41) and Rosetti (n = 36) techniques. Pre- and postoperative control of 24 h pH and lower esophageal sphincter pressure (LESP) in 19 laparoscopically treated patients showed normalization of LESP in all cases and postoperative 24 h pH < 4 ranging between 0 and 3%. CONCLUSIONS: Laparoscopic and reflux surgery is effective for the treatment of reflux esophagitis. Follow-up results compare well with open surgery. PMID- 7777809 TI - Medical management of chronic pancreatitis. AB - Chronic pancreatitis should be considered in all patients with unexplained abdominal pain. The importance of small duct disease without obvious radiographic abnormalities is an important new concept. Diagnostic evaluation should begin with simple, non-invasive, inexpensive tests (serum trypsinogen) to be followed by more complicated testing (hormone stimulation test) if needed. Enteric-coated pancreatic enzymes are the drugs of choice for treating steatorrhea, while conventional non-enteric coated enzymes are preferred for managing pain. The somatostatin analogue octreotide may become an important therapy for treating abdominal pain unresponsive to pancreatic enzyme therapy. Endoscopic approaches to the treatment of chronic pancreatitis are experimental and may cause damage to the pancreas. Surgical ductal decompression is appropriate in selected patients. PMID- 7777810 TI - Endoscopic management of recurrent and chronic pancreatitis. AB - Endoscopic therapy is now being utilized in the setting of recurrent acute and chronic pancreatitis. This review analyzes the current state of the art of these new applications of endoscopy. Selection of appropriate candidates for the various treatment modalities appears important for optimal results of therapy. Patients with gallstone pancreatitis, pancreas divisum, obstructing main pancreatic duct stones, and bulging pseudocysts appear to be the best candidates for endoscopic therapy. PMID- 7777811 TI - Quality of gastric ulcer healing. Is it influenced by antiulcer drugs? AB - BACKGROUND: Chronic administration of sucralfate (SCR), a non-systemic ulcer healing drug, exerts a trophic action on the gastric mucosa and prevents or reduces ulcer recurrence. The aim of this study was to determine whether SCR and/or the acid inhibiting drug omeprazole (OME) may affect the quality of ulcer healing, i.e., restoration of mucosal architecture. METHODS: Gastric ulcers were produced in male rats by serosal application of acetic acid. Rats were gavaged twice daily for 14 days with 2 ml of: (a) Placebo (PLA), (b) SCR 500 mg/kg, or (c) OME, 50 mg/kg starting 48 h after ulcer induction. We determined ulcer size under a dissecting microscope, and performed quantitative histologic assessment of quality of healing score (QS) on a scale from 0 (normal) to 5 (most abnormal). RESULTS: Ulcer size was 1.4 +/- 0.15 mm in the PLA group, 0.61 +/- 0.1 mm in the SCR group and 0.86 +/- 0.13 mm in the OME group (both OME and SCR p < 0.01 versus PLA). In the PLA group, histology showed (in rats with ulcers) a well-developed ulcer margin with cystically dilated glands. The QS of the ulcer scar in the PLA group was 3.3 +/- 0.22. IN the SCR-treated group, within the scar gastric glands were less dilated, more vertically oriented and the healing zone and granulation tissue were well developed and organized. The QS was 1.6 +/- 0.2, p < 0.001 versus PLA and OME. In the OME group, the ulcer margin and the scar were thinner reduction of mucosal thickness by 43 +/- 2% (p < 0.005) and 18 +/- 1%, respectively, versus SCR and PLA groups. The number of dilated glands and connective tissue components in the scar was increased by 60%. The QS was 3.6 +/- 0.3. CONCLUSIONS: (1) Both SCR and OME significantly reduced the size of the experimental gastric ulcer. (2) Restoration of mucosal architecture, assessed quantitatively, was much better in the SCR than in the OME and PLA-treated groups. (3) a trophic action of SCR on the gastric mucosa may be the basis of better quality of ulcer healing with SCR. PMID- 7777812 TI - Sexual and physical abuse and gastrointestinal illness. AB - BACKGROUND: Clinicians are becoming aware of the increased attention paid to the occurrence of sexual and physical abuse in our society and its consequences. However, only recently has attention been paid to their association with medical and particularly gastrointestinal illnesses. METHODS AND RESULTS: Recently, we investigated the frequency of sexual or physical abuse among female patients in our gastroenterology clinic, and their association with health status. Of 206 women, 89 (44%) reported some type of sexual or physical abuse in their lifetime. We also found that patients diagnosed with functional GI disorders when compared with those with organic diagnoses reported a significantly greater frequency of sexual (53% versus 37%) and physical abuse (13% versus 2%). Of these, 59% had never discussed the abuse experience outside their families, a third had never told anyone, and only 17% of their GI physicians were aware of this history. We also found that abuse history led to a poorer health outcome: more severe GI pain and a higher frequency of pelvic pain (16% versus 6%), more non-GI symptoms (7.1 versus 5.8), more physician visits in the previous six months (4.2 versus 3.3) and more lifetime operations (2.8 versus 2.0). CONCLUSIONS: In a GI referral practice, abuse history is a hidden factor that is associated with poorer adjustment to illness, greater symptom severity and higher health care use rates. Since the publication of these data, several groups have supported our findings and obtained additional new data on associating factors and possible mechanisms of symptom generation. This paper will: (i) review this epidemiologic data, (ii) propose hypotheses about their association, (iii) offer suggestions to identify this information in a sensitive and supportive manner, and (iv) discuss how to initiate referral for ancillary psychosocial care. PMID- 7777813 TI - New techniques for liver transplantation: reduced-size, split-liver, living related and auxiliary liver transplantation. AB - Mortality among patients on a waiting list for orthotopic liver transplantation continues to be 10-15%; this is of particular concern in the pediatric population and may become more problematic in adult patients as longer waiting lists for cadaveric transplantation accrue. The longer cold ischemia times afforded by use of University of Wisconsin (UW) solution and improved hepatic surgery techniques have allowed the development of reduced-size liver transplantation (RSLT), split liver transplantation (SLT), and living-related liver transplantation (LRLT). These new surgical techniques have been predominantly employed in children, up to 40% of whom may be candidates for one of these modified procedures. With the exception of SLT, these approaches have been associated with comparable rates of biliary tract and vascular complications, rejection episodes and graft and patient survival when compared to whole organ transplantation. Right hepatic lobe graft recipients have approximately 15% decreased graft survival rates, limiting the acceptance of SLT as a standard approach to decrease waiting list times. Application of LRLT to the adult population, where 5-10% of recipients are potential candidates, is expected to increase. Over 100 LRLTs have been performed worldwide and while recipient survival with LRLT is excellent, concerns about donor morbidity and mortality, psychosocial factors and reimbursement issues remain obstacles. Living-unrelated liver transplantation and auxiliary orthotopic partial liver transplantation are developing approaches to be considered only in highly selected cases. PMID- 7777814 TI - [From risk assessment to risk communication]. PMID- 7777815 TI - [Retrospective overview of contributions to the radioactivity studies specialty]. PMID- 7777816 TI - [Nordenham--memories lead poisoning]. PMID- 7777817 TI - [Formaldehyde--toxicologic aspects]. PMID- 7777819 TI - [Maximum exposure values for substances in the environment as an measurement of environmental health]. PMID- 7777820 TI - [Prevention of water pollution of the Rhine river--from the thiodan accident until today]. PMID- 7777818 TI - [Formaldehyde--public health related aspects of building construction regarding toxicology]. PMID- 7777821 TI - [The effect of night time airplane noise on excretion of stress hormones in residents living near airports]. PMID- 7777822 TI - Osteoporosis: a matter of concern to rheumatology! PMID- 7777823 TI - Pelvic pain and low back pain in pregnant women--an epidemiological study. AB - BACKGROUND: Pelvic Pain in Pregnancy (PPP) has been diagnosed increasingly often in Norway. The relation to Low Back Pain (LBP) is unclear. METHODS: The answers to 5,400 questionnaires were collected from Norwegian women shortly after delivery, and the occurrence of PPP and LBP in relation to various characteristics was studied. RESULTS: 21% of primipara had had both PPP and LBP, whereas 51% had had neither. The figures in multipara were 31% and 33%. After stratification by parity the frequency of both types of pain decreased with increasing age. The largest occupational risk factor of PPP and/or LBP was having to twist or bend several times an hour. This may be preventable. Partial regression coefficients for parity, smoking, and weight of newborn were significantly larger with PPP than with LBP. CONCLUSION: The association of PPP and LBP to occupational exposure was similar. The statistical explanatory pattern, and thus possibly the etiology, is different in the two conditions. PMID- 7777824 TI - Mental health status in systemic lupus erythematosus. AB - Mental health status was assessed in 43 SLE patients and 32 healthy controls applying the GHQ-30 version of The General Health Questionnaire. A 46.5% prevalence of non-psychotic psychiatric disturbance was found in SLE patients compared to 15.6% in the control group (p = 0.01). Factor analysis displayed that SLE patients reported far more depression and difficulty in coping compared to controls. In SLE patients, impaired mental health showed significant associations to several disease associated neurological manifestations, as well as to disease activity. The results indicate that the disease itself influences the psychological well being in a substantial number of patients with SLE. PMID- 7777825 TI - IgM, IgA, and IgG rheumatoid factors in early rheumatoid arthritis predictive of radiological progression? AB - The significance of IgM, IgA and IgG rheumatoid factors (RF) for the prediction of radiological progression, and as process variables during follow-up, was evaluated in a three-year prospective study of 149 patients with early rheumatoid arthritis (symptoms < 1 year at study entry). The occurrence of IgA-RF and IgG-RF at study entry without simultaneous occurrence of IgM-RF, and the seroconversion from RF-negative at entry to RF-positive during follow-up appeared to be unusual. A significant correlation was found between each of the RF-isotype levels at entry and radiological progression after three years. However, no significant prognostic value of IgA-RF and IgG-RF could be demonstrated if analysed in combination with IgM-RF, initial disease activity (as measured by C-reactive protein level), initial radiologic score, HLA-DR4 and HLA-DR2. Although IgM-RF levels generally reflected the course of disease activity and did so better than IgA-RF and IgG-RF levels, their clinical significance as process variables appeared to be limited compared to C-reactive protein. PMID- 7777826 TI - Rheumatoid factor and HLA antigens in wrist tenosynovitis and humeral epicondylitis. AB - A matched case-referent study was undertaken to assess whether rheumatoid factor (RF) is associated with repeating tenosynovitis or peritendinitis and whether HLA B27 predisposes to epicondylitis. The study subjects consisted of 25 workers in manually strenuous jobs with a history of at least two episodes of tenosynovitis or peritendinitis in the wrist or forearm, or humeral epicondylitis, and their matched referents. The latex agglutination test was positive in seven of the 23 cases with tenosynovitis and in one of the referents (p = 0.03). The corresponding figures for IgM-RF by enzyme immunoassay were ten and two, respectively (p = 0.008). HLA-B27 antigen was found in five of the 13 workers with epicondylitis and in one worker with no such history (p = 0.13). It is possible that RF-positive repeating tenosynovitis represents an incomplete form of rheumatoid disease. PMID- 7777827 TI - The risk of cancer in rheumatoid patients in Japan. AB - In order to clarify the risk of cancer development in patients with rheumatoid arthritis (RA), the incidence of malignant tumors during a follow-up period was investigated in RA patients at the Center for Adult Diseases, Osaka, Japan. Six hundred and fifty-five eligible rheumatoid patients (131 males, 524 females) who were admitted to our institute between 1980 and 1989 were matched against the files of the Osaka Cancer Registry. Among them, a total of 26 patients (5 males, 21 females) were noted to have developed some kinds of cancer. The female RA patients demonstrated a significantly higher incidence of all cancers than the general population, with an observed/expected (O/E) ratio of 1.71 (95% confidence interval = 1.06-2.62). Cancer of the buccal cavity/pharynx and thyroid cancer also showed a higher incidence in female RA patients, with O/E ratios of 12.93 and 2.74, respectively. PMID- 7777828 TI - Comparative evaluation of anti-heat shock protein antibodies in SLE and healthy controls. AB - Presence of anti-heat shock protein (anti-hsp) antibodies have earlier been demonstrated in children as well as adult patients with systemic lupus erythmatosus (SLE). Since hsp share homology across several species, it is presumed that anti-E. coli antibodies could in fact be autoantibodies. Surface expression of hsps has also been shown to play a role in the generation of antibodies. In the present study antibodies to a recombinant hsp70 of Leishmania dnonvani origin have been investigated in patients with SLE and data compared with the incidence in control sera. One clone from the cDNA library of Leishmania donovani confirmed previously to be expressing hsp70, cloned in pBluescript and antibodies to the expressed protein were checked by ELISA and western blot assays. The results indicate the presence of anti-hsp70 antibodies in 22/26 (85%) SLE patients and 12/20 (60%) control sera. Our observations reconfirm the presence of antibodies to hsp in normal controls and therefore they may not bear any direct relation to the pathogenesis of SLE. PMID- 7777829 TI - Increased frequency of the C4A*6 rare allele in rheumatic heart disease. AB - The aim of the present investigation was to determine whether the alleles of the MHC class III complement proteins BF, C2 and C4 (C4A and C4B) could be markers for RHD in the Brazilian population. Forty-nine patients with chronic RHD were studied. The controls included 65 healthy unrelated individuals, matched with the patients according to sex, age and ethnical background. BF, C2, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variants with monoclonal and policlonal antibodies. The results showed a significantly elevated presence of the C4A*6 rare allele (p = 0.003 RR = 11.85) and a decrease of C4A*3 in the patients. In addition, C4 null and BF and C4 rare alleles were more frequent in patients than in the controls. Considering that in this investigation only RHD patients were included, further studies are necessary in order to clarify whether C4A6 is a marker for the cardiac form or for the disease itself. PMID- 7777830 TI - Correlations between PAF-acether and tumor necrosis factor in rheumatoid arthritis. Influence of parenteral corticosteroids. AB - The aim of this study was to evaluate the presence of PAF-acether (PAF), its specific degrading enzyme acetylhydrolase, and tumor necrosis factor (TNF) concentrations in blood and synovial fluid (SF) from patients with active RA. The variations of the mediators were also evaluated after corticosteroid perfusions in 7 patients. Lipo-PAF (PAF complexed to lipoproteins) was the main form of PAF detected both in blood and in SF, whereas unbound PAF was uncommon. Acetylhydrolase activity was also present in SF, with a strong correlation between serum and SF levels. TNF was detected in most of the samples, and TNF and acetylhydrolase levels were strongly correlated both in blood and in SF. Despite dramatic clinical improvement, corticosteroid treatment was not accompanied by a significant reduction of the concentration of blood mediators, suggesting that these molecules should not be considered as markers of disease activity. PMID- 7777831 TI - The variable clinical picture of arthritis induced by human parvovirus B19. Report of seven adult cases and review of the literature. AB - Seven patients with arthritis due to infection with human parvovirus B19 are reported, and the literature association reviewed. B19 virus arthritis most frequently affects young to middle aged women and occurs predominantly during the first six months of the year. The majority of cases have oligoarthritis or polyarthritis, and the joints most often involved are the proximal interphalangeal joints and knees. Of the seven patients reported, one case developed systemic lupus erythematosus, one case evolved into erosive, seropositive rheumatoid arthritis while one case was subsequently diagnosed as undifferentiated connective tissue disease. PMID- 7777832 TI - A prospective evaluation of antithyroid antibody prevalence in 100 patients with rheumatoid arthritis. AB - The prevalence of thyroid antibodies in 100 patients with rheumatoid arthritis in Northern Norway was studied. The serological data were compared with those from a major population survey in the same area. Compared to the prevalence in the normal population, the present study demonstrates that patients with rheumatoid arthritis have a higher prevalence of antibodies to both thyroid microsomal antigen and thyroglobulin. PMID- 7777833 TI - Sepsis and tumor emboli mimic vasculitis. AB - An unequivocal diagnosis of vasculitis typical of polyarteritis was made in a sixty one year old male. At post mortem no vasculitis was found, but there were widespread microabscesses and tumour emboli from an occult adenocarcinoma of the caecum. The importance of considering other pathologies which may mimic vasculitis is emphasised. PMID- 7777834 TI - Pseudoporphyria due to naproxen. A cluster of 3 cases. AB - Pseudoporphyria is a photo-induced blistering disorder with increased skin fragility, caused among others by nonsteroidal antiinflammatory drugs. Lesions heal with scarring and milia. Porphyrin screen studies are normal in this disease. Histology and immunofluorescence resembles porphyria cutanea tarda. In this report we describe a cluster of three cases of naproxen-induced pseudoporphyria, and review briefly previously reported cases induced by naproxen. The majority of reported cases involve children. Physicians should be aware of this reversible skin disorder. PMID- 7777835 TI - [Ethology and good health in pets]. AB - Ethology, or the comparative study of behaviour and its biological roots, has made significant contributions to our understanding of companion animal behaviour and thereby, the welfare of these animals. Ethological questions, concepts and methods can be readily applied to companion animal studies and the interpretation of results. In particular, comparison of behaviour shown in a 'reference system' with that exhibited in more restricted environments has proven very useful. Although emphasis has been placed on farm animals in the past, more and more animal protection laws require that regulations and guidelines, including those concerning companion animals, be based upon sound ethological studies. It is only through such observations that we can objectively determine what 'species typical' behaviour is and what the animal's 'needs' are. Based upon these, recommendations for proper housing conditions can be made, which in turn reduce the number of cases where behavioural disturbances tarnish the relationship between humans and their companion animals. Using past research on the domestic cat and human-cat interactions, the author illustrates these points and makes suggestions for future research. PMID- 7777836 TI - [Malignant melanoma in two cats]. AB - Malignant melanomas with extensive metastasis in various organs were diagnosed in a 8-year-old European shorthair cat and a 10-year-old Persian cat. The primary tumor in the European shorthair cat was located within the eye. The clinical progress, gross pathology and histology are outlined. The possibility of an increase of melanomas in combination with FIV- or FeLV-infections is discussed. PMID- 7777837 TI - [Lung tumor with unusual metastasis in a cat--a case report]. AB - Metastasis of an adenocarcinoma was diagnosed histologically in a foot pad biopsy of a cat exhibiting progressive locomotion problems, foot pad swelling and nail loosing. A bronchial gland adenocarcinoma was identified as primary tumour at necropsy. Metastases were found in all foot pads, the kidneys and various lymph nodes. A review of the literature and of the own necropsy reports an affinity of bronchial gland carcinoma metastases to skeletal muscles and bones, especially digital bones. Non-respiratory signs as lameness, foot pad swelling and nail loss appear to predominate clinically whereas respiratory signs are observed only in about one third of all cases. PMID- 7777838 TI - [Multiple congenital heart abnormalities in a boxer: a case report]. PMID- 7777839 TI - Neuronal vacuoles in the canine brain. AB - Intraneuronal vacuoles have been observed in the motor trigeminal nucleus of the medulla oblongata of two dogs which showed neurological deficits. Its significance and possible relation with the same lesions observed in other animal species are discussed. PMID- 7777840 TI - [What is your diagnosis? Hypoadrenocorticism in a domestic cat]. PMID- 7777841 TI - Spinal cord injury and pregnancy: the stories of two women. AB - This article describes some of the experiences encountered by two women with spinal cord injuries (SCI) during pregnancy. Pregnant women, with or without a SCI, encounter some common experiences. Common complaints of pregnancy for both include urinary tract infections, sleep problems, and constipation. Complaints specific to those women with a SCI centered around issues such as increased urinary incontinence, autonomic dysreflexia and delayed wound healing. The women with SCI neither developed pressure areas nor experienced premature deliveries, major complications predicted by literature. Women with SCI have felt that they were victims of inadequate environmental designs that hindered their mobility and inhibited their independence. Many of the psychosocial aspects studied proved to be common to pregnant women in general and not specific to individuals with spinal cord injury. PMID- 7777842 TI - Comparison of seat pressures on three bowel care/shower chairs in spinal cord injury. AB - Pressure, positioning, and postural support are critical aspects in the design of a new bowel care/shower chair for persons with spinal cord injuries (SCI). The purpose of this evaluation was to evaluate seating pressures on three existing bowel care/shower chairs commonly used by persons with spinal cord injuries. A pressure mapping device, the Force Sensing Array, was used to measure seat pressure, position and postural support. Three seated subjects with spinal cord injuries were evaluated on each of the following three bowel care/shower chairs: Lumex, TRAUM-AID and E&J. The results of this evaluation will be briefly presented. This study is part of a larger study to design a bowel care/shower chair that uniquely meets the needs of persons with spinal cord injury. PMID- 7777843 TI - Basing practice on nursing research. PMID- 7777844 TI - Presidential address: instead of resisting change, we accepted it. PMID- 7777845 TI - Endourethral prosthesis for treatment of detrusor sphincter dyssynergia: impact on quality of life for persons with spinal cord injury. AB - Neurogenic bladders with detrusor sphincter dyssynergia (DSD) are common in persons with spinal cord injury and with multiple sclerosis. Treatment options such as sphincterotomy, urethral foley and suprapubic catheters are not without complications or failure; however, they are recommended for patients who are unable to do intermittent catheterization. An endourethral prosthesis for DSD has been developed for experimental use in the United States. We report one year results of the clinical trials with endourethral prostheses implanted in ten patients. Initial subjective and objective results show an 80% success rate. At present, preliminary data show that an endourethral prosthesis, which is simple to insert and has few complications, appears to offer an alternative to conventional treatment. A key to success is to prepare for changes in life style that impact the patient's quality of life. Both patient and staff education are necessary pre-operatively to achieve successful outcomes post-operatively. PMID- 7777846 TI - Genetic chimerism. PMID- 7777847 TI - Quantitative trait locus for reading disability: correction. AB - In the news article "Can risky mergers save hospital-based research?" by Wade Roush (19 May, p. 968), the statement that University Hospitals of Cleveland rose from 20th in the rankings of teaching hospitals funded by the National Institutes of Health (NIH) in 1991 to 12th at present was incorrect. In fact, it was Case Western Reserve University (CWRU), with which University Hospitals of Cleveland is affiliated, that received $69 million in NIH grants in 1993, making it the 20th largest recipient of such grants among medical centers; the university then received $97 million in 1994, raising its rank to 12th. About $15 million of the increase, or 53%, was attributable to CWRU's 1992 affiliation with Henry Ford Hospital in Detroit. Other hospitals affiliated with Case Western include MetroHealth Medical Center, Mount Sinai Medical Center, St. Luke's Medical Center, and Cleveland Veterans' Affairs Medical Center. PMID- 7777848 TI - Germany warily maps genome project. PMID- 7777850 TI - Closing in on the complete yeast genome sequence. PMID- 7777849 TI - Russia readies its first gene law. PMID- 7777852 TI - Gathering airs schemes for averting asteroid doom. PMID- 7777851 TI - Imanishi-Kari case. Marathon hearing gets under way. PMID- 7777853 TI - France. AIDS expert charged in HIV-blood case. PMID- 7777854 TI - Mapping the cell's nucleus. PMID- 7777855 TI - Can one type of HIV protect against another type? PMID- 7777856 TI - Linked regularities in the development and evolution of mammalian brains. AB - Analysis of data collected on 131 species of primates, bats, and insectivores showed that the sizes of brain components, from medulla to forebrain, are highly predictable from absolute brain size by a nonlinear function. The order of neurogenesis was found to be highly conserved across a wide range of mammals and to correlate with the relative enlargement of structures as brain size increases, with disproportionately large growth occurring in late-generated structures. Because the order of neurogenesis is conserved, the most likely brain alteration resulting from selection for any behavioral ability may be a coordinated enlargement of the entire nonolfactory brain. PMID- 7777857 TI - Extreme discordant sib pairs for mapping quantitative trait loci in humans. AB - Analysis of differences between siblings (sib pair analysis) is a standard method of genetic linkage analysis for mapping quantitative trait loci, such as those contributing to hypertension and obesity, in humans. In traditional designs, pairs are selected at random or with one sib having an extreme trait value. The majority of such pairs provide little power to detect linkage; only pairs that are concordant for high values, low values, or extremely discordant pairs (for example, one in the top 10 percent and the other in the bottom 10 percent of the distribution) provide substantial power. Focus on discordant pairs can reduce the amount of genotyping necessary over conventional designs by 10- to 40-fold. PMID- 7777858 TI - Identification of a stimulator of steroid hormone synthesis isolated from testis. AB - Gonadal steroidogenesis is regulated by pituitary gonadotropins and a locally produced, unidentified factor. A 70-kilodalton (kD) protein complex secreted from rat Sertoli cells was isolated. The complex, composed of 28- and 38-kD proteins, stimulated steroidogenesis by Leydig cells and ovarian granulosa cells in a dose dependent and adenosine 3',5'-monophosphate-independent manner. The follicle stimulating hormone-induced 28-kD protein appeared to be responsible for the bioactivity, but the 38-kD protein was indispensable for maximal activity. The 28 and 38-kD proteins were shown to be identical to the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the proenzyme form of cathepsin L, respectively. Thus, a TIMP-1-procathepsin L complex is a potent activator of steroidogenesis and may regulate steroid concentrations and, thus, germ cell development in both males and females. PMID- 7777859 TI - Association of increased spontaneous mutation rates with high levels of transcription in yeast. AB - Complex processes such as transcription, replication, repair, and recombination require changes in chromatin structure and the interactions of numerous trans acting factors with DNA sequences, raising the possibility that these processes may be interrelated. Here the effect of transcription on the rate of spontaneous mutation in the yeast Saccharomyces cerevisiae was examined. With the use of a lys2 frameshift allele under the control of a highly inducible promoter, the rate of spontaneous reversion was shown to increase when the mutant gene was highly transcribed. Thus, transcriptionally active DNA and enhanced spontaneous mutation rates are associated in yeast. PMID- 7777860 TI - Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. AB - Cells from patients with ataxia telangiectasia (AT) are hypersensitive to ionizing radiation and are defective in the regulation of DNA synthesis. A complementary DNA that corrects the radiation sensitivity and DNA synthesis defects in fibroblasts from an AT group D patient was isolated by expression cloning and shown to encode a truncated form of I kappa B-alpha, an inhibitor of the nuclear factor kappa B (NF-kappa B) transcriptional activator. The parental AT fibroblasts expressed large amounts of the I kappa B-alpha transcript and showed constitutive activation of NF-kappa B. The AT fibroblasts transfected with the truncated I kappa B-alpha expressed normal amounts of the I kappa B-alpha transcript and showed regulated activation of NF-kappa B. These results suggest that aberrant regulation of NF-kappa B and I kappa B-alpha contribute to the cellular defect in AT. PMID- 7777861 TI - A nuclear-encoded form II RuBisCO in dinoflagellates. AB - The chloroplasts of most dinoflagellates are unusual in that they are surrounded by three membranes and contain the carotenoid peridinin. The ribulose-1,5 bisphosphate carboxylase-oxygenase (RuBisCO) in dinoflagellate chloroplasts was found here to also be unusual. Unlike other eukaryotes, dinoflagellates containing peridinin use a form of RuBisCO (form II) previously found only in some species of proteobacteria. Furthermore, this RuBisCO is not encoded in the chloroplast DNA, as is the case in other organisms, but is encoded by the nuclear DNA. The unusual nature of this enzyme and location of its gene support the idea that dinoflagellate chloroplasts may have had a distinctive evolutionary origin. PMID- 7777862 TI - Presynaptic component of long-term potentiation visualized at individual hippocampal synapses. AB - Long-term potentiation has previously been studied with electrophysiological techniques that do not readily separate presynaptic and postsynaptic contributions. Changes in exocytotic-endocytotic cycling have now been monitored at synapses between cultured rat hippocampal neurons by measuring the differential uptake of antibodies that recognize the intraluminal domain of the synaptic vesicle protein synaptotagmin. Vesicular cycling increased markedly during glutamate-induced long-term potentiation. The degree of potentiation was heterogeneous, appearing greater at synapses at which the initial extent of vesicular turnover was low. Thus, changes in presynaptic activity were visualized directly and the spatial distribution of potentiation could be determined at the level of single synaptic boutons. PMID- 7777863 TI - Integration of visual and linguistic information in spoken language comprehension. AB - Psycholinguists have commonly assumed that as a spoken linguistic message unfolds over time, it is initially structured by a syntactic processing module that is encapsulated from information provided by other perceptual and cognitive systems. To test the effects of relevant visual context on the rapid mental processes that accompany spoken language comprehension, eye movements were recorded with a head mounted eye-tracking system while subjects followed instructions to manipulate real objects. Visual context influenced spoken word recognition and mediated syntactic processing, even during the earliest moments of language processing. PMID- 7777864 TI - Dukes C2 colon cancer: what is appropriate follow-up? PMID- 7777865 TI - The biology of hematopoietic stem cells. PMID- 7777866 TI - High-dose therapy with stem cell infusion in lymphoma. PMID- 7777867 TI - Transplantation in multiple myeloma. PMID- 7777868 TI - Peripheral blood stem cell transplant in breast cancer. PMID- 7777869 TI - High-dose chemotherapy and hematopoietic progenitor cell support for patients with epithelial ovarian cancer. PMID- 7777870 TI - Complications of peripheral blood stem cell transplantation. PMID- 7777871 TI - Peripheral blood stem cell transplant: future directions. PMID- 7777872 TI - Peripheral blood progenitor cell generation and harvesting. PMID- 7777873 TI - Lessons learned from Hurricane Andrew: recommendations for care of the elderly in long-term care facilities. AB - We report on the experience of a 500-bed, long-term care facility in Miami, Fla, which provides housing and nursing care units for patients--ranging from those who are independently ambulatory to those who are acutely ill and feeble--in preparing for, during, and in the immediate aftermath of Hurricane Andrew, which struck on August 24, 1992. The problems encountered included a massive influx of evacuated elderly to the facility, facility isolation, loss of electrical power, loss of running water, special dietary needs, and limited professional staffing due to personal property losses or loss of transportation. Overwhelmed county emergency medical services, limited access to hospitals and patient care, and difficulty in procuring supplies exacerbated the already complicated situation resulting from the storm. As a result of these catastrophic conditions, a number of challenges specific to the care of the elderly were identified. In conjunction with the Florida Department of Elder Affairs, we drafted a comprehensive blueprint that could serve as a disaster plan for other long-term care facilities facing a similar threat during the hurricane season. PMID- 7777874 TI - Understanding federal medical device statutes and their application to various penile prostheses. AB - Medical devices have become an important component of our professional armamentarium. This paper exposes the practitioner to the Food and Drug Administration and its control over medical devices. Specifically, the 1976 amendment to the Food and Drug Administration Acts is described, along with the subsequent federal laws. Because of all the new technology available, physicians should be aware of the applicable laws and regulations. In addition, a review of the penile prosthesis includes its history and evolution, as well as the entire product line available for use. Attention is directed to the problems that have arisen from malfunctioning components. PMID- 7777875 TI - Hurricane Andrew-related injuries and illnesses, Louisiana, 1992. AB - To determine the extent and types of injuries and illnesses in Louisiana associated with or related to Hurricane Andrew, we gathered data from hospital emergency departments and coroner's offices on demographic variables, institution, nature and cause of the injury or illness, body part affected, location, and date and time of the event. A hurricane-related injury or illness was defined as one that occurred from noon on August 24, 1992, through midnight on September 21, 1992, as a direct or indirect result of the preparation for (preimpact), the impact of, or the clean-up after the hurricane (postimpact). Nineteen parishes in south-central Louisiana that were most affected by Hurricane Andrew provided data from patients seen in emergency departments and reports from coroner's offices. Active, advance surveillance of this type promotes and facilitates the reporting of disaster-related health outcomes. Future planning for hurricanes should take into account the high rate of cuts, lacerations, and puncture wounds, particularly during the postimpact phase. PMID- 7777876 TI - Epilepsy surgery: removing the thorn from the lion's paw. AB - In the United States, 10,000 to 20,000 patients have epilepsy uncontrolled by medication. The addition of a second-line drug to the primary regimen has a 2% to 11% chance of controlling the seizures. We present a series of 35 patients with intractable epilepsy who had surgical resection of their seizure focus. Seventy five percent of the patients with temporal lobe epilepsy were made seizure free, with an additional 14% sustaining a greater than 90% reduction in seizures (decrease in number and frequency). Seventy-one percent of the patients with extratemporal lobe epilepsy (seizures originating outside the temporal lobe) had a worthwhile reduction (> 90%) in their seizures. Two patients sustained permanent clinically significant deficits as a result of their presurgical evaluation or resection. There were no deaths. Epilepsy surgery offers a cure for the "incurable" patient with a morbidity of 5% to 6%. PMID- 7777877 TI - Significance of solitary and multiple esophageal ulcers in patients with AIDS. AB - We endoscopically evaluated odynophagia and/or dysphagia in 23 patients with acquired immunodeficiency syndrome (AIDS). Eleven patients (48%) were found to have esophageal ulcers. Seven of them had deep, sharply demarcated, well circumscribed ulcer craters with raised edges; in two the ulcer extended to the muscularis propria. Ulcers were single in four patients, multiple in six, and unspecified in one. Biopsies were nondiagnostic. In eight patients, mycobacterial, viral, and fungal cultures were negative. Specific infections diagnosed in three patients were treated with appropriate agents. Ulcers were treated symptomatically, and seven patients received therapy for suspected viral etiology. Symptoms remained unchanged in five patients, improved in three, and resolved in two. Fifty-five percent of patients died within 3.6 months (mean) of diagnosis. Large solitary and multiple esophageal ulcers are common in AIDS patients with odynophagia and dysphagia. PMID- 7777878 TI - Alfentanil for conscious sedation during colonoscopy. AB - This investigation was designed to determine whether the narcotic alfentanil, a relatively new fentanyl derivative with rapid onset of action and offset of activity, alone or in combination with midazolam has advantages over the traditional meperidine and midazolam regimen for conscious sedation. Thirty-five subjects were randomized to receive an initial dose of narcotic and sedative with additional narcotics or sedatives administered as needed. Subjects receiving no midazolam sedative (alfentanil and placebo group, n = 13) had less desaturation and had the need for supplemental oxygen less often than those receiving alfentanil and midazolam (n = 11) or meperidine and midazolam (n = 11). There were no differences as assessed by patient and colonoscopist for tolerance and discomfort, procedure ease, recovery time, complications, electrocardiogram, and blood pressure. Baseline evaluation did not predict the need for supplemental oxygen. We concluded that alfentanil, with or without a sedative, has no advantage over the commonly used meperidine and midazolam regimen. PMID- 7777879 TI - Myelolipoma of the adrenal gland: a case report. AB - Adrenal myelolipomas are rare benign neoplasms composed of mature fat and bone marrow elements. Most are asymptomatic tumors found incidentally at postmortem examinations. We report the natural history of an adrenal myelolipoma in a middle aged man over a 6-year interval. PMID- 7777880 TI - Extra-adrenal myelolipoma: report of two cases. AB - Myelolipomas are benign tumors composed of an admixture of mature adipose tissue and normal hematopoietic cells. The vast majority occur within the adrenal glands, but several extra-adrenal myelolipomas (EAMLs) have been reported. The typical EAML is a solitary, well-defined mass within the abdomen, most commonly in the retroperitoneal presacral area. EAMLs may produce symptoms related to their mass effect, but they are occasionally incidental findings. Most commonly, the patient is older than 40 years and has no hematologic abnormalities. It is important to distinguish EAMLs from other soft tissue tumors, in particular liposarcomas, myxoid malignant fibrous histiocytomas, and extramedullary hematopoietic tumors. We discuss two cases of EAML. The first was in the retroperitoneum of a 76-year-old woman. It is the largest EAML ever reported, measuring 26 cm x 15 cm x 11 cm. The second, a presacral mass in a 68-year-old man, was diagnosed preoperatively by percutaneous computed tomography-guided fine needle aspiration biopsy. Preoperative diagnosis facilitated surgical management in this case. We discuss the clinical, radiologic, and pathologic characteristics and the differential diagnosis of this rare entity. PMID- 7777881 TI - Gold pulmonary toxicity in a patient with a normal chest radiograph. AB - We report a case of gold pulmonary toxicity in a patient with adult-onset Still's disease with dyspnea on exertion and a normal chest radiograph. Withdrawal of gold therapy resulted in complete resolution of pulmonary toxicity in our patient without the need for additional steroid therapy. PMID- 7777883 TI - Disseminated histoplasmosis in a patient from a nonendemic area who has acquired immunodeficiency syndrome. AB - Disseminated histoplasmosis is a serious opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS), often seen as the first manifestation of the syndrome. However, cases are reported almost exclusively from patients who live in or have traveled to endemic areas. We describe a case of disseminated histoplasmosis in a black woman with a 50-lb weight loss and marked weakness that occurred over a 6-month period. This case is one of the few in which disseminated histoplasmosis occurred as the first manifestation of AIDS in a patient in a nonendemic area. We believe it to be the first case reported in Michigan in which the patient has no history of prior residence in an endemic area. Disseminated histoplasmosis should be suspected in patients with AIDS and unexplained febrile illness, even in nonendemic areas. PMID- 7777882 TI - Intramural gastric actinomycosis. AB - We report a case of intramural gastric actinomycosis and review the features of the additional 16 cases of this uncommon infection reported in the literature. The patient had gastrointestinal symptoms, weight loss, and fever after gastric operation. At laparotomy, an infiltrating gastric tumor-like lesion was found. Histology revealed actinomycosis, and the patient was successfully treated with oral penicillin. Because of its rarity, intramural actinomycosis is an entity overlooked by most surgeons. Reporting of such cases may help increase the awareness of this important and curable disease. PMID- 7777884 TI - Hepatic iron overload associated with self-medication. AB - A patient with the incidental finding of an elevated serum ferritin level was found to have hepatic iron overload associated with iron injections. Liver disease is an example of one of the potential complications of folk remedies or patient self-medication that physicians may encounter, especially along the US Mexican border. PMID- 7777886 TI - Perforation of a Meckel's diverticulum during laparoscopic cholecystectomy. AB - Laparoscopic procedures incur risks and complications that differ from their "open" counterparts. Although rare, injury to asymptomatic umbilical remnants (eg, Meckel's diverticulum) is one of these unique complications. PMID- 7777885 TI - Progressive pulmonary cryptococcosis in a patient who is immunocompetent. AB - Pulmonary cryptococcal disease can have variable clinical and roentgenographic presentations. Symptoms and radiographic abnormalities can resolve prior to therapy, even in a patient who is immunocompromised. Antifungal therapy is generally not recommended for a patient who is immunocompetent with nonprogressive, nondisseminated pulmonary cryptococcosis. We present a case of pulmonary cryptococcosis that progressed despite fluconazole therapy in a patient who was immunocompetent. This appears to be the second reported case of a discrete endobronchial cryptococcoma. PMID- 7777887 TI - Torsion, necrosis, and inflammation of an epiploic appendix of the large bowel: a diagnostic and therapeutic dilemma. AB - We present the case of a young patient with abdominal pain of 3 weeks' duration and a preoperative presumptive diagnosis of acute appendicitis, diverticulitis, colon perforation, or possibly neoplasm. Even after resection of a large mass involving the right colon, the diagnosis was not confirmed until surgical pathology identified torsion, partial necrosis, and inflammation of an epiploic appendix of the right colon. PMID- 7777888 TI - Tracheoesophageal fistula as the initial presentation of Hodgkin's disease. PMID- 7777889 TI - Training room evaluation of chest pain in the adolescent athlete. AB - A physician or athletic trainer will often be faced with an athlete complaining of chest pain during or after an event. Chest pain in children and adolescents is usually of a noncardiac origin; only 5% of cases are due to cardiac problems. With a properly documented history and physical evaluation, one can usually identify the etiology of the chest discomfort or at least rule out any serious difficulties. The various diagnostic possibilities include cardiac, musculoskeletal, pulmonary, gastrointestinal, and psychiatric causes of pain. We discuss several specific conditions, as well as the signs, symptoms, and basic management. PMID- 7777890 TI - Association of systemic lupus erythematosus and gluten enteropathy. AB - Systemic lupus erythematosus presents various clinical manifestations. The coexistence of systemic lupus erythematosus and celiac sprue has been rarely reported. We present a patient who had systemic lupus erythematosus with malabsorption demonstrating characteristic clinical and pathologic findings of celiac sprue (gluten enteropathy). PMID- 7777891 TI - Primary lymphoma of the liver mimicking metastatic liver disease. AB - Primary lymphoma of the liver is rare. In the 50 previously reported cases in the literature, computed tomography usually showed a solitary, bulky hypodense area in the liver. We report a case of primary lymphoma of the liver presenting multiple lesions in the liver and clinical and biochemical evidence suggestive of metastatic adenocarcinoma of the liver. PMID- 7777892 TI - Multiple symmetrical lipomatosis: computed tomographic appearance. AB - In a case of localized multiple symmetrical lipomatosis (Madelung's disease), we examined the cervical fat accumulation by computed tomography. We describe the radiographic features of this process and briefly review the pathophysiology of this rare disorder. PMID- 7777894 TI - To care for health. PMID- 7777893 TI - Microangiopathic hemolytic anemia as an initial presentation of metastatic cancer of unknown primary origin. AB - Microangiopathic hemolytic anemia (MAHA) is a well-documented but rare complication of disseminated cancer; it usually occurs in the late or terminal stage of cancer. We describe a case of metastatic carcinoma of unknown origin in which MAHA was the initial presentation. A 36-year-old woman came to our hospital with lower back pain and progressive exertional dyspnea for 8 weeks. Hemolytic anemia, thrombocytopenia, and leukoerythroblastosis were found on admission. The peripheral blood smear revealed polychromasia, poikilocytosis, and many schistocytes. Bone marrow biopsy disclosed metastatic carcinoma. After careful workup, we failed to find the primary site of cancer. The anemia and thrombocytopenia responded dramatically to combination chemotherapy with 5 fluorouracil, mitomycin C, and cisplatin. This case indicates that metastatic carcinoma should be included in the differential diagnosis in previously healthy patients with MAHA. PMID- 7777895 TI - Health system reform: whither the academic medical center? PMID- 7777896 TI - Overheating of drugs during shipping and storage. PMID- 7777897 TI - Altered responses to medications exposed to excessive temperatures during shipping. PMID- 7777899 TI - Tuberculous mastitis. PMID- 7777898 TI - Fingerstick glucose determination and CPR. PMID- 7777900 TI - Human genetic disease in Asia. PMID- 7777901 TI - Perspectives of using Euphorbia splendens as a molluscicide in schistosomiasis control programs. AB - A total of 1,426 species of plants had been tested in order to find out a vegetal derived molluscicide against the vectors of Schistosoma mansoni. Euphorbia splendens is one of the most promising molluscicides. In this article we briefly present the main aspects that have to be considered to use this plant as a molluscicide, which include some agricultural aspects and operational methods for application. This can be done by the extraction of the active principles (millaminas) present in the latex or in the raw juice obtained through total maceration of plants. The culture of E. splendens, which spreads out by vegetative sprouts, showed an annual average growth of 30 cm. After 1.5 years the average productivity of crude latex with a DL90 of 12 ppm concentration, was 1 liter by 8m2 by cultivated area. This amount is enough to treat a volume of water of 97,200 liters. A comparative analysis between the cost of snail control through synthetic molluscicides was carried out based upon the data presented by Jobim (1979) for six controlling methods in several countries, and some cost aspects for E. splendens. This analysis was done considering a geographic parameter expressed by the index cubic meters of treated habitat per square kilometer, from which we can obtain an estimate dimension of the geographic area to be cultivated with E. splendens necessary to treat the same volume of water treated by synthetic molluscicides. PMID- 7777902 TI - Epidemiological studies of malaria at Pong Nam Ron, eastern Thailand. AB - Malaria is still a serious health problem in Thailand. Present attempts at controlling the disease by drug treatment and other means remain unsatisfactory. Thus, development of vaccination against malaria is a major research goal of malaria immunology. The objective of this study was to acquire epidemiological base line data for subsequent vaccine trials. A cross-sectional descriptive survey was conducted among 451 local inhabitants during the beginning of the transmission season in June 1989 at Pong Nam Ron District, Chanthaburi Province, Eastern Thailand where malaria transmission was likely to be high. Following the cross-sectional survey weekly morbidity surveillance was started to detect new cases of malaria by using active and passive case detection at the district hospital, local health centers and at neighboring malaria clinics. Entomological observations were made monthly to determine inoculation rates. Forty-six percent of the population were male and 54% female; one third were under the age of 15 and 14% under the age of 5 years. Eighty percent of the adults were married. Sixty percent of the subjects interviewed gave a history of malarial illness in the past. Malaria, malnutrition, abnormal hemoglobin diseases and parasitic infestation were the main health problems in the study area. The annual parasite incidence of malaria was 149.6/1,000 population and two-thirds of them were asymptomatic indicating a semi-immune condition among these subjects. It was difficult to interpret the results of entomological studies due to low density of the malaria vector. PMID- 7777903 TI - Field evaluation of simplified radioactive and nonradioactive DNA probe methods for the diagnosis of falciparum malaria. AB - Specific DNA probe hybridization technique is one method of choice for detection of malaria infection. It provides an obvious advantage over conventional microscopy when large numbers of samples are simultaneously monitored. The method was simplified so that preparation and processing of blood specimens were all performed on membrane filters. Background signals generated from blood components were removed by treating samples spotted on the membrane with a series of buffer washes without the necessity of a protease digestion step. Hybridization was monitored using either 32P-or digoxigenin-labeled DNA probe. 849 field samples collected from various malaria endemic areas in Thailand have been evaluated by this protocol and compared with microscopic examination. Sensitivity obtained by this procedure was comparable to that of microscopy at a malaria clinic. The specificities of both types of DNA probes were better than 93%, but digoxigenin labeled probe performed better than 32P-labeled one when the numbers of parasites were less than 25 per 200 white blood cells. PMID- 7777905 TI - Significance of blood coagulation and platelet profiles in relation to pulmonary thrombosis in beta-thalassemia/Hb E. AB - In beta-Thalassemia hemoglobin E (beta-thal Hb E), hypoxemia with abnormal lung function was described and postmortem examination in these patients showed organized pulmonary trombi with thickened arterial wall, particularly in post splenectomized cases. Coagulation and platelet profiles were studied in 58 beta thal Hb E patients. In 35 cases with intact spleen, the fibrinolytic activity was significantly decreased with high antithrombin III activity, while coagulation tests revealed mild abnormality. The platelet aggregation to ADP, adrenaline, collagen and ristocretin were defective and platelet 5-hydroxytryptamine content was lower than normal. Twenty-three patients who had been splenectomized for 5-18 years, decreased fibrinolytic activity and high antithrombin III activity were also observed. The coagulation profiles and platelet aggregation in response to ADP, adrenaline and collagen showed better results. Fourteen cases exhibited thrombocytosis and their thrombin generation was in the hypercoagulable range. Platelet aggregation in response to ristocetin remained defective and platelet 5 hydroxytryptamine content was lower than in cases with intact spleens. Defective aggregation to ristocetin would indicate abnormal von Willebrand's factor (vWF). Decreased fibrinolysis should very likely have a role in the occurrence of thrombosis and the better hemostatic profiles in post-splenectomized cases would contribute to the more frequent thrombotic incidence in these cases. PMID- 7777904 TI - Exotoxin profiles of Campylobacters isolated in Malaysia. AB - Approximately 57% of clinical and 33% of poultry isolates examined produced a cytotoxin. Cytotoxic activity was detected in 25 (50%) isolates of Campylobacter of which 12 were isolated from bloody diarrhea and 9 from watery stools. The cytotoxin titers were low, ranging from 2 to 16. The crude filtrates from 50 Campylobacter isolates showed no cytotoxic effect in Vero cells, no fluid accumulation in suckling mice and no hemolytic activity. PMID- 7777906 TI - The increasing importance of vitamin B12 deficiency as a contributing factor to anemia in Malaysia. AB - A comparative study was done to determine the profile of vitamin B12 and folate status in Malaysians during two different periods. For the period of 1987/88, we analysed a total of 9,162 cases (inpatients) referred for vitamin B12 estimation and 10,290 cases for folate estimation. We found that 2.6% were vitamin B12 deficient and 31.2% were folate deficient. For the period of 1992/93, of the 9,962 cases assayed, 8.2% were found to be vitamin B12 deficient whereas 7.6% of the 10,355 cases referred were folate deficient. Vitamin B12 and folate were assayed either using microbiological or radioassays. These findings indicate that there appears to be a change in the status of both vitamin B12 and folate over the five year interval. PMID- 7777907 TI - Hookworm anemia in the adult population of Jagapati village, Bali, Indonesia. AB - A cross sectional study was conducted in Jagapati Village, Bali to assess some characteristics of hookworm anemia among the adult population. Hookworm anemia was defined as an iron deficiency anemia in heavily infected individuals (EPG > 2,000). WHO criteria for anemia and criteria of Hercberg for iron deficiency were used. In this study, 15 cases of hookworm anemia were found among 454 total samples (3.3%), or among 123 cases of iron deficiency anemia (12.2%). The age varied between 16-69 years with male to female ratio of 1:2.8. Twelve cases were found with symptoms and signs of anemia, 1 case with full blown hookworm anemia, and 2 cases were asymptomatic. The hemoglobin level was found to be 4.5-12.9 g/dl, with 12 cases (80.0%) being classified as mild anemia, 2 cases (13.3%) as moderate anemia, and 1 case as severe anemia. The mean serum iron level was 39.6 mg/dl, mean transferrin saturation was 11.1%, and mean serum ferritin level was 9.6 ng/dl. Hypoalbuminemia was found in 9 cases (60.0%), eosinophilia in 8 cases (53.3%), and low serum folic acid level in 5 cases (38.5%). High total serum IgE level was found in all but one case, with mean total serum IgE level of 3,739 U/ml. The intensity of hookworm infection was moderate in 11 cases (73.3%) and severe in 4 cases (26.7%). It could be concluded that hookworm anemia was characterized by iron deficiency anemia with eosinophilia, high serum total IgE level, hypoalbuminemia and moderate to severe hookworm infection. PMID- 7777908 TI - Detection by immunoblot assay of antibodies to Taenia solium cysticerci in sera from residents of rural communities and from epileptic patients in Bali, Indonesia. AB - Several studies from Bali have indicated the presence of Taenia solium. Relatively little has been reported, however, implicating human exposure to this parasite on Bali based upon the prevalence of anti-T. solium antibodies in asymptomatic and epileptic individuals. This study was conducted to determine by immunoblot assay and ELISA the frequency of anti-cysticercus antibodies in two groups of Balinese. Among 746 residents of four ecologic zones, 94 (13%) were positive by immunoblot. Of 74 epileptic patients from throughout the island, 10 (14%) were positive by immunoblot and 8 (11%) by ELISA; however, only 4 (22%) of the 18 sera positive in either test were positive in both assays. The previously defined high specificity and sensitivity of immunoblot indicates that T. solium cysticercosis is well established in Bali and that a significant amount of epilepsy may be due to neurocysticercosis. PMID- 7777909 TI - Intestinal parasitoses in the Kandy area, Sri Lanka. AB - The prevalence of intestinal protozoa and geohelminths was assessed among two diverse populations in the Kandy area: adults attending medical outpatients clinics at the Teaching Hospital Peradeniya, and pre-school children in low-cost housing areas within the Kandy Municipality. In addition to a brief history and examination, a fresh stool sample was obtained and examined by direct smears in saline and iodine, and by formol-ether concentration. The children's stool samples were also examined for Cryptosporidium by cold Ziehl-Neelsen staining. A total of 192 stool samples from the adult outpatients (101 males, age range 15-82 years, mean 51.4 years) and 354 samples from the pre-school children (age range 1 72 months, mean 30 months) were examined. Entamoeba histolytica was not seen in any of the samples; Giardia cysts and Cryptosporidium oocysts were seen in three and one sample respectively from the pre-school children. The overall prevalence of geohelminth infections was 21.3% among the adults and 24.5% among the children. Ascaris lumbricoides was the predominant species in both populations. Comparison of the rate of intestinal parasite infection among 37 adult patients patients with non-specific abdominal complaints, with the rate among 37 matched controls with no abdominal complaints showed no significant difference (16% and 19% respectively). This suggests that the presence of abdominal pain or diarrhea was unrelated to the presence of intestinal parasites in the adult study population. Although the techniques used were not highly sensitive, the absence of E. histolytic probably reflects a true decline in the prevalence of this parasite in Sri Lanka.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7777910 TI - Quetelet index, hemoglobin and parasitic infection of rural women in northeast Thailand. AB - The Quetelet index, hemoglobin and parasitic infection rates of adolescent and young women from 21 villages in Northeast Thailand were assessed. Data were collected in the hot, rainy and cold seasons of the year. The proportion of undernourished females varied between 10 and 15% when a cut-off point of 18.7 of the Quetelet index was chosen. 23 to 33% of the women had hemoglobin levels below 12 g%. Parasitic infection rates with various intestinal helminths were high but not related to the nutritional status or anemia. PMID- 7777911 TI - Seroepidemiological study of toxoplasmosis in two different geographical areas in Nepal. AB - A total of 302 serum samples collected from Chitawan (159) and Mustang (143) districts of Nepal were included in this study. Anti-toxoplasma antibody was detected using micro-latex agglutination (MLA) and ELISA methods. An overall positive rate was found to be 57.9%. The positive rate in Chitawan was significantly higher (64.1%) (less than 1,000 m altitude) compared to that in Mustang (51.0%) (more than 3,000 m altitude) (p < 0.05). Females in Chitawan showed significantly higher positive rate (71.2%) compared to males (56.9%) (p < 0.05). On the contrary, though insignificantly, males showed higher positive rate (57.9%) compared to that of females (43.3%) in Mustang. Almost equal positive rate was observed among males in both study area. Females in Chitawan showed significantly higher (71.2%) positive rate compared to their counterparts in Mustang (43.3%) (p < 0.001). A slight increase in positive rate with age was observed in Chitawan while in Mustang a decreasing trend was noticed. Ethnically though statistically not significant, Indo-Aryans showed a higher positive rate (69.2%) compared to the positive rate shown by Tibeto-Burmans (63.1%) in Chitawan while the reverse was true in Mustang (Tibeto-Burmans: 53.8% and Indo-Aryans: 38.4%). Interestingly, 2.9% and 1.3% of MLA positive samples showed toxoplasma IgM antibody. None of the IgM positive samples were positive for toxoplasmic antigens. PMID- 7777913 TI - Blastocystis hominis infection, a cause of human diarrhea. AB - Blastocystis hominis has long been described as a non pathogenic protozoan parasite until recently when claims have been made that it can result in pathogenic conditions. Of the 729 stool samples (614 from survey and 115 from pediatric wards) examined, 18.1% of them were found to be positive for one or more intestinal protozoan cyst. The commonest was Giardia intestinalis (8.4%) Followed by Entamoeba coli (7.1%) and Entamoeba histolytica (5.1%) in the normal children without symptoms of diarrhea. When diarrheic stools were examined, the commonest parasite encountered was Giardia (20.4%), followed by E. coli (15.9%) and E. histolytica (9.7%). Blastocystis was observed in 4.4% of the children who had diarrhea and 1.1% among the children taken from the normal population in the rural areas. PMID- 7777912 TI - Distribution of anti-Toxoplasma gondii antibodies among Orang Asli (aborigines) in Peninsular Malaysia. AB - The distribution of anti-toxoplasma antibodies among the aborigines in Malaysia and its association with other soil transmitted infections and eosinophilia were studied. A total of 415 serum samples were collected and tested by IFA test. Overall prevalence was 10.6%, lower than previously reported. The antibody titers showed a unimodal distribution peaking at 1:8 dilution. There was a higher proportion of high antibody titer (> 1:128) in the adult compared to the children with no significant difference in prevalence rate by sex. The pattern of infection does not differ from other soil transmitted infections and there was no association between raised Toxoplasma antibodies with eosinophilia. PMID- 7777914 TI - Enterobius vermicularis infection among children aged 1-8 years in a rural area in Malaysia. AB - The infection rate and relationship of enterobiasis with socio-economic status were determined in children aged 1-8 years, living in a rural area in Malaysia. Of the 178 subjects 40.4% were infected with Enterobius vermicularis. The distribution of enterobiasis among these children were analyzed in relation to age groups and sex. The rate of infection was significantly higher in older children (5-7 years). The association of enterobiasis with other factors studied such as number of persons per house, household income per months and mother's employment status were not significant. The sensitivity of three successive days anal swabs compared to a single swab was found to be statistically significant. PMID- 7777915 TI - Occurrence of the infective stage of Angiostrongylus cantonensis in the yellow tree monitor (Varanus bengalensis) in five Provinces of Thailand. AB - Twenty-two yellow tree monitors (Varanus bengalensis) were trapped and transported from 5 provinces, namely Lampang, Phitsanulok, Kamphaeng Phet, Tak and Prachin Buri to look for the infective larvae stage of Angiostrongylus cantonensis. In 4 provinces all of the yellow tree monitors were infected with the infective stage larvae of A. cantonensis altogether. Twenty-one of the 22 yellow tree monitors (95.5%) in the five provinces were infected. Our results of this study extend our knowledge of natural prevalence of A. cantonensis in yellow tree monitors. The snail eating habit of the yellow tree monitor might possibly be the source of the larvae. PMID- 7777916 TI - Ultrastructural observations on cercaria of Schistosoma japonicum. AB - The present paper describes the ultrastructure of the surface topography, head organ, tegument, musculature, glandular system, primary alimentary tract and flame cells of the Chinese mainland strain of Schistosoma japonicum cercaria, as visualized with both scanning and transmission electron microscopes. The results not only illustrate the morphological features of the cercarial surface and its internal structure reflecting an adaptation to the aqueous habitat but also reveal the correlation between the morphological structure and physiological function. PMID- 7777917 TI - Studies on host-parasite relationship between the Puerto Rican strain of Schistosoma mansoni and Biomphalaria snails. AB - Immunoelectrophoretic studies on common antigenicities were carried out by using rabbits sera immunized with the Puerto Rican strain of Schistosoma mansoni adult worms or eggs and antigens of several adult Biomphalaria snails and vice versa. As the result, S. mansoni adult worm extracts produced 8 bands both with extracts of Biomphalaria glabrata pigmentation and B. glabrata pigmentado, 3 to 4 bands with those of B. glabrata albino and 1 to 2 bands with those of B. straminea. On the other hand, S. mansoni egg extracts produced 5 bands with extracts of B. glabrata pigmentation, 4 bands with those of B. glabrata pigmentado, 2 bands with those of B. glabrata albino and 1 band with those of B. straminea. In the experimental infection of adult Biomphalaria snails with five S. mansoni miracidia, the infection rate in B. glabrata pigmentation was 78.8%, and 71.2% in B. glabrata pigmentado, whereas the infection rate in B. glabrata albino was 10.3%, and B. straminea was not susceptible to S. mansoni. The infectivity of each snail corresponded with the number of bands representing common antigenicities between host and parasite. Crude antigens of Biomphalaria snails were fractionated by Sephadex G-100 column, and each antigen fraction was tested with anti-S. mansoni adult worm and egg sera by immunoelectrophoresis. The common antigenicities between fractionated antigens of Biomphalaria snails and of ani-S. mansoni adult worm or egg sera mostly existed in the first fraction 1 with Mr > 45 kDa. PMID- 7777918 TI - Cumulative exposure and its relationship with chronic filarial disease in bancroftian filariasis. AB - Several hypotheses have been put forth about the factors influencing the dynamics of infection and disease in lymphatic filariasis. However, appropriate validation of these hypotheses by real situation analyses of epidemiological data is lacking. The present analyses examine the relationship between cumulative exposure to infection and prevalence of disease by utilizing the existing entomological and clinical data collected between 1981 and 1986 in Pondicherry, South India, endemic for bancroftian filariasis. While there was a significant negative association when the cumulative exposure was correlated with total prevalence of disease (r = 0.70, p = 0.024) as well as hydrocele alone (r = 0.74, p = 0.014), a significant positive association was found with prevalence of lymphedema (r = 0.72, p = 0.018). These results suggest that hydrocele development follows early after exposure, but prolonged exposure could result either in development of lymphedema or immune tolerance resulting in microfilaremia. These could also suggest that the pathomechanisms in development of hydrocele and lymphedema could follow different pathways. Implications of the present findings are discussed in light of the various hypotheses put forward by earlier studies. PMID- 7777919 TI - Composite fish culture for mosquito control in rice fields in southern India. AB - Composite culture of edible fishes (common carp, Cryprinus carpio; silver carp, Hypopthalmithys molitrix, grass carp, Ctenopharyngodon idella; catla, Catla catla; rohu, Labeo rohita; and mrigal, Cirrhinus mrigala) in rice fields in the Cauvery delta of Tamil Nadu, southern India, resulted in 81.0% reduction in the immature mosquito population of anophelines and 83.5% of culicines. Analysis of fish feces for mosquito larval head capsules showed that common carp and silver carp are effective larvivores. The selective feeding of common carp on culicines and silver carp on anophelines is correlated to their trophic niches. Net profit in the fish-cum-rice fields was 2.5 times greater than fields in which rice alone was cultured. Hence, rice-cum-fish culture can be recommended to the farming community in this area. PMID- 7777920 TI - Comparative susceptibility of Periplaneta americana (L) to five pyrethroid insecticides. AB - Five pyrethroids namely, lambda-cyhalothrin, permethrin, deltamethrin, cyfluthrin and alpha-cypermethrin were evaluated using adult male and female cockroaches, Periplaneta americana (L). The American cockroaches were exposed for 10 minutes to glass jars treated with different concentrations of the five pyrethroids. The cockroaches were susceptible to all five pyrethroids and the susceptibility based on LC50 and LC50 were observed to be in the following order: lambda-cyhalothrin > permethrin > deltamethrin > cyfluthrin > alpha-cypermethrin The results showed that lambda-cyhalothrin was the most effective and alpha-cypermethrin was the least effective against Periplaneta americana (L). PMID- 7777921 TI - Adult population differences in response to six insecticides in Culex fuscocephala Theobald. AB - Adult bioassay was conducted in the laboratory on two populations of Culex fuscocephala, a vector of Japanese encephalitis (JE) in India, against two organochloride compounds (DDT and dieldrin), an organophosphate compound (malathion), a carbamate pesticide (propoxur) and two synthetic pyrethroids (deltamethrin and cyfluthrin) using WHO techniques. The adult populations from Mandya an irrigated agricultural area, and Mysore, a non-agricultural place in Karnataka, India, have been employed for the experiments. JE outbreaks were reported from these places at different times. Among the insecticides used malathion in 5% concentration was found to be the most effective while, cyfluthrin (0.05%) and deltamethrin (0.025%) were very effective in much lesser concentration. For both propoxur (0.1%) and DDT (4.0%) the two populations of Cx. fuscocephala expressed least susceptibility in terms of the LT50. Against dieldrin (0.4%), cyfluthrin, DDT and malathion Mysore population showed relatively more susceptibility than Mandya population. However for deltamethrin and propoxur the Mandya population registered less tolerance than the Mysore population. Thus adult population responses to different insecticides are variable in the present study. PMID- 7777922 TI - Effect of sublethal dosages of insecticides on chikungunya virus susceptible and refractory strains of Aedes aegypti. AB - Three strains of Aedes aegypti mosquitos viz (i) CRS, refractory to Chikungunya (CHIK) virus by oral route of infection but susceptible to DDT (2) CSS, susceptible to CHIK virus and also susceptible to DDT (3) CSS-DDTR, susceptible to CHIK virus but resistant to DDT, were examined for the effect of sublethal dosages of DDT and deltamethrin on their fecundity. Biochemical analysis showed that there was an increase in glutathione s-transferase activity in the CSS-DDTR strain which was associated with DDT resistance. There was an increase in acetylcholinesterase activity in the CRS strain, however it was not associated with resistance to all the three insecticides tested. No significant differences in the fecundity of these three strains were observed, though there was some increase in the number of non layers in CSS-DDTR strain after the treatment of DDT and mean number of eggs laid by CSS and CRS strains was slightly reduced (0.5 > p < 0.1) after the treatment with deltamethrin. PMID- 7777923 TI - Breeding of Aedes aegypti (L.) and Aedes albopictus (Skuse) in urban housing of Sibu town, Sarawak. AB - An Aedes survey using various larval survey methods was conducted in 12 urban housing areas and 29 vacant lands in Sibu town proper. Aedes albopictus larvae were found in all areas surveyed while Aedes aegypti larvae were present in 10 localities and 4 vacant lands. There were no significant difference in the house index, breteau and larval density index of these two Aedes (Stegomyia) species from the survey areas. The proportion of containers positive with Ae. aegypti and Ae. albopictus in area outside the house compound and near the house fencing were 3.2 times higher than outdoor compound. The indoor/outdoor breeding ratio for Ae. aegypti alone is 1.6:1. The most preferred breeding habitats outdoor were plastic cups and used tires while indoor habitats were ant traps and flower vases. In the vacant lands, the average number of larvae per containers was significantly higher than in houses and over 51% of the containers inspected were positive. Shared breeding between Ae. aegypti and Ae. albopictus larvae accounted for 9% in house surveys and 4.5% in vacant land survey. The use of various methods in Aedes larval survey may provide essential information in the study of vector epidemiology in dengue and dengue hemorrhagic fever transmission. PMID- 7777925 TI - Dengue-3 (16562) PGMK 33 vaccine: neurovirulence, viremia and immune responses in Macaca fascicularis. AB - Investigation of monkey neurovirulence of dengue-3 viruses (DEN-3, 16562) was undertaken to provide an evaluation of the relative safety of virus strain attenuated for potential use of live virus vaccine. Ten flavivirus-negative, cynomolgus monkeys (Macacafascicularis) were used in the test. The animals were inoculated intrathalamically, intraspinally and intramuscularly with DEN-3 PGMK 33 attenuated live virus vaccine (6 monkeys): parent virus (2) and control cell culture fluid (2). Blood samples were collected on days 0, 1, 2, 4, 6, 8, 10, 12 and 21 for virus isolation and days 0 and 21 or 22 for serologic testing. One monkey with DEN-3 (16562) PGMK 33 candidate vaccine had detectable viremia on day 10. By day 21, all recipients of PGMK 33 and both monkeys with DEN-3 parent virus developed serum neutralizing antibodies to DEN-3 titers ranged from 56-320. The monkeys showed no evidence of illness and none died of dengue infection. Histopathological examination of tissue collected on day 21 or 22 revealed only minimal neurovirulence lesions as scored by the routine grading system. No differences were observed between the DEN-3 parent and vaccine viruses and it is concluded that neither virus is neurovirulent for cynomolgus monkeys. PMID- 7777924 TI - Early mental and neurological sequelae after Japanese B encephalitis. AB - Japanese B encephalitis is a disease with high mortality and many of those surviving suffer from serious sequelae. During the 1992 epidemic in northern Vietnam 50 patients treated at the Institute for Protection of Children's Health in Hanoi were studied concerning the type of sequelae and the development of the symptoms during the first two months of the disease. The age span was 1 to 15 years. 29 of the patients (58%) did not recover fully during the observation period. Fifteen (30%) showed signs of both neurological and mental disturbances. Nine (18%) only had mental symptoms while 5 (20%) suffered from isolated neurological sequelae. EEG was pathological in 9 out of 30 tested cases (30%); 9 of 23 patients (39%) performed subnormal IQ tests. Deep coma, bronchopneumonia with cyanosis, apnea attacks, prolonged fever and coma were all correlated (without statistical significance) to a higher risk for subsequent sequelae. PMID- 7777928 TI - Vaccine-preventable disease susceptibility in a young adult Micronesian population. AB - Current US military recruit vaccination policy presumes that recruits have had a complete childhood immunization series. This assumption may not be appropriate for recruits from Micronesia, who may have had limited access to modern health care, including immunization programs. During 1988 and 1990, a cross-sectional serosurvey was conducted among 66 US military recruits, 56 from the Federated States of Micronesia and 10 from the Republic of the Marshall Islands, collectively referred to as Micronesia. Antibody seronegativity levels for 12 vaccine-preventable (or potentially so) diseases were: measles (52%), mumps (14%), rubella (21%), varicella (38%), diphtheria (39%) tetanus (0%), polio type 1 (4%), polio type 2 (0%), polio type 3 (14%), hepatitis A (9%), hepatitis B (17%), and hepatitis C (98%). Compared with Army recruits in general, Micronesian recruits were significantly more likely to be seronegative for measles and varicella and seropositive for hepatitis types A and B. Personal histories of disease were felt to be inadequate in predicting antibody status. PMID- 7777927 TI - Poliomyelitis and measles serosurvey in northern Malaysia. AB - In 1990 the Institute for Medical Research carried out a serosurvey in the state of Kelantan to study the age stratified immune prevalence rates for measles and poliomyelitis. Our findings indicate that 981 out of 1,097 (89%) of the population screened had measles antibodies and more than 90% (366 out of 400) had antibodies to all three serotypes of poliovirus. The susceptible group for measles was infants below one year of age, of whom 53.3% (8/15) did not have measles antibody. Of 400 subjects, 125 (31.3%) who were either incompletely vaccinated or had not been vaccinated against poliomyelitis, had polio neutralizing antibodies to all three poliovirus serotypes, suggesting herd immunity in the population. No high risk age group could be identified for poliomyelitis. PMID- 7777929 TI - Endemic goiter in the Lemanak and Ai river villages of Sarawak. AB - In a survey of 974 villagers (408 males, 566 females; ages = 11-82 years) of the Ai (n = 496; 212 males, 284 females) and Lemanak (n = 478; 196 males, 282 females) rivers in the district of Lubuk Antu in Sarawak's Sri Aman Division during July 1993, goiter was found in 31.8% of the subjects. The goiter prevalence was higher in the more interior Ai river area than in the Lemanak river area (36.9% vs 26.5%). In females aged 15 years and above, the goiter prevalence was 75.4% and 49.1%, respectively, in the Ai and Lemanak river areas. The difference in goiter prevalence between the two areas was related to the degree of iodine deficiency in the two areas. The median urinary iodine excretion in the Ai river villagers was 22.1 micrograms/l compared to 72.9 micrograms/l in the Lemanak river villagers (p < 0.0001). Goitrous subjects tended to have lower urinary iodine concentration than non-goitrous subjects. In the males, smoking of tobacco was associated with a two-fold increase in goiter frequency. Despite on going distribution of iodized salt by the medical and health services in the State, only 23% of the 135 salt samples obtained from the households in the areas contained detectable iodine. PMID- 7777926 TI - Storage stability of dengue IgM and IgG antibodies in whole blood and serum dried on filter paper strips detected by ELISA. AB - Blood specimens from 133 patients clinically diagnosed as dengue virus infection by physicians in Nakhon Phanom Hospital, Thailand, were examined to detect anti dengue IgM and IgG antibodies by antibody capture ELISA. The blood specimens were divided into 3 types of storage; (1) frozen serum aliquots, (2) whole blood dried on filter paper strips, and (3) sera dried on filter paper strips. These specimens were stored for the periods of 1, 3, 4, and 5 months, at -20 degrees C in the case of frozen serum aliquots, or at room temperature in the case of specimens dried on filter paper strips, before examined in paralleled by the ELISA. Anti-dengue IgG antibodies were stable for at least 5 months of storage as dried whole blood or serum on filter paper strips. So were the anti-dengue IgM antibodies in the dried whole blood from secondary dengue cases. Anti-dengue IgM antibodies from primary dengue cases declined slowly in whole blood and more rapidly in serum, both dried on filter paper strips. In the serum dried on filter paper strips, even anti-dengue IgM antibodies from secondary cases decreased significantly on storage. We suggest that diagnosis on dengue infections by IgM capture ELISA should be performed within 1 month after the test specimens are collected as whole blood, not as serum, when the filter paper method is used for sample collection. PMID- 7777930 TI - Hospital admissions due to acute poisoning in the New Territories, Hong Kong. AB - To study the pattern of acute poisoning in the New Territories East of Hong Kong, 291 adult cases admitted to the Prince of Wales Hospital in 1989 were reviewed. The female-to-male ratio was 2.3 to 1 and the majority of patients (83%) were below the age of 40. The main poisons involved were hypnotics and sedatives (44.3%), household products (14.8%) and analgesics (10%). The poisoning was intentional in the majority of cases (98.6%). A specific antidote was necessary in 5.2% of cases. Four patients died after admission giving an overall mortality of 1.4%. When compared to the findings from other western countries, important variations in the pattern of acute poisoning were seen in Hong Kong. Firstly, a substantial proportion of drugs ingested were not dispensed labeled although their nature could usually be determined. Secondly, "Dettol", a household antiseptic, was commonly used in self-poisoning episodes. The lack of drug identification labeling on dispensed medicines outside hospitals is of great concern to all physicians in Hong Kong. PMID- 7777931 TI - Socio-demographic characteristics and health status of urban Thai elderly. AB - Socio-demographic and health status of 205 elderly aged 60-90 years who attended a special clinic for the elderly at Rajvithi Hospital were investigated. All of the subjects had no major complaints and seemed to be apparently healthy. Socio economic situation, life-style pattern and other health related information was assessed. Nearly all of the elderly lived with their relatives. Quite a high number of the females had never attended school. Almost 60% of the elderly had no regular income. The health situation of the individuals under investigation seemed to be satisfactory. The majority did not smoke and did not drink alcohol. There are indications that in the future more of the elderly population will stay alone and will face economical problems because of the absence of general social security scheme for Thailand. PMID- 7777932 TI - Knowledge, attitudes and practices of mothers on childhood acute respiratory infections (ARI). AB - A total of three hundred mothers in both rural and urban areas were interviewed and their knowledge, attitude and practice (KAP) on acute respiratory infections (ARI) were compared. It was observed that KAP on ARI of mothers in both categories was almost the same with the exception of their health care seeking practice. Most had traditional beliefs as to the cause of ARI with only a minority knowing the causes. Only one third of mothers knew signs and symptoms of pneumonia; the majority had not experienced the fatal danger sign, chest indrawing and could not recognize it. As regards health care seeking practices, private general practitioners were identified as favorite health providers in urban areas. Utilization of government health facilities was higher among rural mothers. Self medication was found to be common in both categories of mothers, with western medicine being the top of the list. PMID- 7777934 TI - Capillariasis with chronic intestinal pseudo-obstruction. PMID- 7777933 TI - Meningoencephalomyelitis and neuritis clinically diagnosed as multiple sclerosis. PMID- 7777935 TI - Melioidotic spondylitis mimicking tuberculous spondylitis. PMID- 7777936 TI - Control of intractable gastric hemorrhage by monosodium glutamate. PMID- 7777937 TI - Evaluation of neem oil as sandfly, Phlebotomus papatasi (Scopoli) repellent in an Oriental sore endemic area in Rajasthan. PMID- 7777938 TI - [Forensic expert relevance of imaging examinations in diagnosis of degenerative and occupational diseases of the lumbar spine]. PMID- 7777939 TI - [Pulsating tinnitus in aberrant internal carotid artery combined with abnormal position of the jugular vein bulb. Case report]. PMID- 7777940 TI - [Paravertebral extramedullary hematopoiesis in congenital dyserythropoietic anemia type II (CDA II)]. PMID- 7777941 TI - [Radiotherapy and survival in CNS involvement in non-Hodgkin's lymphoma]. PMID- 7777942 TI - [Area-wide supply of advanced radiologic devices in Bavaria]. PMID- 7777943 TI - [What is the prognosis for patients with recurrent gastric carcinoma?]. AB - The authors discuss the problem of relapses of gastric cancer, the conditions of its development and its possible treatment. As a basis they use experience with the treatment of 167 patients operated on account of this condition at the First Surgical Clinic in Olomouc in 1986-1993. In these patients 77 radical operations were performed, 25 developed a relapse of the tumor. Only in two patients it was possible to perform another resection--total gastrectomy. In these two re resected patients the mean survival period was 9 months, in the remainder only two months. The authors conclude that in relapses of gastric cancer even several months' survival are a success. PMID- 7777944 TI - [Variations in extrahepatic bile ducts, their arteries and pancreatic ducts]. AB - The author presents a brief account of congenital varieties of extrahepatic biliary pathways, a cystica and pancreatic ducts and explains their development. Good knowledge of these varieties is of great importance for detailed preparation in laparoscopic cholecystectomy and during fibroscopic examination of duodenal papillae. PMID- 7777945 TI - [Inguinal hernia surgery in 1993 in Slovakia]. AB - The authors present an account of a survey (by questionnaires) focused on surgery of inguinal hernias. The recovery rate of questionnaires was 84%. The standard techniques in surgery of child hernias are Gross (29%) and Girard (29%). In primary hernias more than 50% are made by Bassini's and Girard's plastic operation. So far the worldwide accepted plastic operation of Shouldice is rarely used 14%. In the techniques of relapsing hernias also inadequate plastic operations are used; the ratio of Lichtenstein's plastic operation which has the lowest relapse rate is only 4.5%. PMID- 7777946 TI - Infected late false aneurysm of the superficial femoral artery. Case-report. AB - A 24-year-old Croatian soldier sustained a comminuted fracture of the femur and after stabilization with AO external fixation an infected late false aneurysm of the superficial femoral artery developed. The aneurysm was extirpated and the artery reconstructed using the saphenous vein. PMID- 7777947 TI - [Right-sided pneumothorax--a complication of laparoscopic cholecystectomy]. AB - In a 49-years old woman cholecystolithiasis was confirmed by sonography and she was admitted for laparoscopic cholecystectomy. During the operation right-sided pneumothorax developed as a result of the injury of diaphragma by monopolar electrocautery. Operation was converted and the injury was treated by continuous suture. Carbon dioxide was spontaneously resorbed from thoracic cavity during the 5 days following the operation without tube thoracostomy. The operating wound was healed per primam and the patient was discharged on the 14th postoperative day. PMID- 7777948 TI - [Modern dressings. Hydrogels]. AB - Hydrogels are occlusive types of dressings. They are three-dimensional nets made up of hydrophil polymers. They can be produced from synthetic or semisynthetic materials or a combination of the two. Hydrogels retain different percentages of water but are themselves insoluble in water. This is why they maintain on the wound surface their structure and do not dissolve. They are suited for the dressing of wounds with low secretion such as grade I and II burns, grade I and II bedsores and above all epithelial defects, major skin abrasions and areas after collection of epithelial grafts. Their use is contraindicated in infected wounds, in wounds with a massive secretion and ulcers of arterial origin. Although the domain of their clinical use are clean granulating or already epithelizing wounds, they are very well suited also for rehydration of dry and black skin necroses. Their advantages include minimal pain in the wound as well as the fact that they can be left on the wound without redressing till complete healing. This is made possible also by the fact that they are translucent. PMID- 7777949 TI - [Personal experience with administration of Zinacef in the form of a "protected coagulum" in patients after heart surgery]. AB - Antibiotic prophylaxis in the form of a so-called protected coagulum is an important part of prevention of postoperative infections in cardiosurgery. The selection of a suitable antibiotic depends on many factors--its effectiveness against the most frequent pathogens, the tissue penetration, undesirable effects. The authors compared two groups of patients operated on account of IHD using prophylaxis with cefalotine (491 patients) and cefuroxime (241 patients). The groups are comparable as to baseline parameters. In the cefuroxime-treated group was a significantly lower incidence of infections of the surgical wound (12.6 % vs. 5.8 %). The number of serious infectious complications (mediastinitis, osteomyelitis) and the incidence of other infections did not differ in the two groups. PMID- 7777951 TI - Academic health service complexes. PMID- 7777950 TI - The use of volatile agents in southern Africa. PMID- 7777952 TI - Practical application of data obtained from a Perinatal Problem Identification Programme. PMID- 7777953 TI - Private sector health care expenditure in South Africa. PMID- 7777954 TI - Putting the records straight--a plea for improved abortion data. PMID- 7777955 TI - Toxaemia--a question of balance. PMID- 7777956 TI - Abortion--a debate. PMID- 7777957 TI - Abortion reform--imperative or outrageous? PMID- 7777958 TI - Confidentiality concerning HIV/AIDS status--the implications of the Appeal Court decision. AB - The Appellate Division recently overturned a Supreme Court judgement concerning the disclosure of a patient's HIV status by his general practitioner to another general practitioner and a dentist. This article examines the content of both judgements with particular reference to its implication for the medical profession, and considers the arguments that may be raised for and against disclosure of a patient's HIV seropositivity. PMID- 7777959 TI - The value of incorporating avoidable factors into perinatal audits. AB - OBJECTIVE: To assess whether incorporating a system of identifying, classifying and grading avoidable factors into a perinatal audit can be useful in identifying problem areas. DESIGN: Descriptive study. SETTING: Black urban population, Pretoria, South Africa. SUBJECTS: All perinatal deaths of infants weighing more than 1,000 g from urban areas served by Kalafong Hospital between August 1991 and July 1992. METHODS: All perinatal deaths were classified according to the primary obstetric cause of death and neonatal cause of death, and whether any avoidable factors were present which could have contributed to the death. RESULTS: The perinatal mortality rate was 26/1,000 deliveries. Avoidable factors occurred in 58% of perinatal deaths. Our problem areas which were immediately remedial were identified as labour management-related problems, administrative problems in obtaining syphilis results, and estimation of fetal weight. Other problem areas which need to be solved are patient education, early attendance at clinics, improved documentation and continuing education of medical personnel. CONCLUSION: The use of this classification of avoidable factors has enabled the detection of problem areas that can be improved immediately at very little cost. PMID- 7777960 TI - Audit incorporating avoidability and appropriate intervention can significantly decrease perinatal mortality. AB - OBJECTIVE: To evaluate the role of the ICA (Identification, Cause, Avoidable factor) Solution method of perinatal audit in reducing perinatal mortality. DESIGN: Retrospective audit of 1,060 perinatal deaths between 1 January 1991 and 31 December 1992. SETTING: Livingstone Hospital Maternity Service. SUBJECTS: One thousand and sixty perinatal deaths, where the gestational age exceeded 28 weeks or, when gestational age was unknown, the birth weight was equal to or exceeded 1,000 g. MAIN OUTCOME MEASURES: All perinatal deaths were identified and classified by primary obstetric cause for perinatal loss. In the second year of the study avoidable factors were sought and, if found, graded and categorised. RESULTS: The major primary obstetric causes of perinatal loss identified and amenable to intervention were intrapartum trauma, intrapartum asphyxia and infection. In the second year of study potentially avoidable factors were sought and identified in almost 50% of perinatal deaths. Appropriate intervention lowered the perinatal mortality rate by 23% (P < 0.05; odds ratio 0.76; 95% confidence interval 0.67-0.86). CONCLUSION: The ICA Solution method of perinatal audit identified problems in overall obstetric care, facilitating a significant fall in perinatal mortality. PMID- 7777961 TI - The impact of the Perinatal Education Programme on cognitive knowledge in midwives. AB - OBJECTIVE: To determine whether the Maternal Care and Newborn Care manuals from the Perinatal Education Programme significantly improves the cognitive knowledge of midwives. DESIGN: Assessment of cognitive knowledge by means of multiple choice testing. These tests were conducted before and after each of the 30 units of the Programme. In addition, a multiple-choice examination was arranged on completion of each of the two manuals. SETTING: Level I, II and III hospitals and level I clinics in urban and rural areas of South Africa. PARTICIPANTS: One hundred and fourteen midwives from hospitals and clinics. INTERVENTION: Maternal and Newborn Care manuals of the Perinatal Education Programme, studied at home and later discussed by the participants in groups every few weeks. MAIN OUTCOMES MEASURED: Number of participants who completed a manual, mean results of the pretests and post-tests, mean results of the final examination, and percentage of participants achieving 80% or more in the pretests, post-tests and final examination. RESULTS: Mean pretest and post-test results for the Maternal Care manual were 65% and 85% respectively. Mean pretest and post-test results for the Newborn Care manual were 72% and 93% respectively. The mean result for the final examination for the Maternal Care manual was 90%, while the mean result for the Newborn Care manual was 95%. There was a significant improvement in cognitive knowledge when either manual was used. CONCLUSION: The cognitive knowledge of both maternal and newborn care can be significantly improved when midwives use the Perinatal Education Programme in an outreach, co-operative learning course. PMID- 7777962 TI - Reregistration of gynaecologists in South Africa--the profession's opinion. AB - OBJECTIVE: Testing of the profession's opinions and attitudes with regard to a possible reregistration system. METHODS: A questionnaire was sent to all the gynaecologists in South Africa to test their opinions and attitudes with regard to reregistration. RESULTS: After two mailings, 62.4% of the 603 gynaecologists had responded. Seventy per cent of the respondents were in private practice while 19% were in full-time academic positions. More than two-thirds (68%) of the respondents resided in a city, close to a medical school. Although 74% were in favour of the implementation of a reregistration system, only 56% were enthusiastic about it. Congress attendance and self-study programmes were the categories in which more than 85% of the respondents would be able to earn points. The general feeling was that such a system should be governed by the profession. CONCLUSIONS: The profession was in favour of a system of reregistration, but great concern was expressed at the contents of such a programme and the manner in which it would be governed. PMID- 7777963 TI - Use of saliva as an alternative to serum for HIV screening in Africa. AB - Saliva has been recommended as a safe and effective alternative to serum for enzyme-linked immunosorbent assay (ELISA) for HIV antibodies in surveillance programmes in developing countries. We evaluated the use of saliva specimens for detection of HIV antibodies using three different commercially available ELISAs. Saliva specimens from 107 patients selected at random from HIV high-risk (38), medium-risk (27) and low-risk (42) areas of the hospital were screened with the Wellcozyme HIV1 + 2 GACELISA VK61 (recommended for use with saliva), Wellcozyme HIV1 + 2 VK54/55 and Wellcozyme HIV-1 recombinant VK56/57. Of the 107 patients, 50 were positive and 57 negative for antibodies to HIV on confirmatory Western blot testing. For detection of antibodies to HIV in saliva, the Wellcozyme HIV1 + 2 GACELISA VK61 had a sensitivity and a specificity of 98%, the Wellcozyme HIV-1 recombinant VK56/57 a sensitivity and specificity of 96%, and the Wellcozyme HIV1 + 2 VK54/55 a sensitivity of 94% and a specificity of 95%. For detection of antibodies to HIV in serum, the Wellcozyme HIV-1 recombinant VK56/57 had a sensitivity and a specificity of 100%, the Wellcozyme HIV1 + 2 GACELISA VK61 a sensitivity and a specificity of 98%, and the Wellcozyme HIV1 + 2 VK54/55 a sensitivity and a specificity of 96%. This study illustrates that saliva can be used as an alternative to serum for screening for anti-HIV antibodies in African patients. PMID- 7777965 TI - Drug policy. PMID- 7777964 TI - Retinal detachment in black South Africans. AB - Rhegmatogenous retinal detachments seen in black patients attending King Edward VIII Hospital Ophthalmology Clinic over a 5-year period from January 1987 to December 1991 were reviewed. Penetrating trauma and diabetic retinopathy were excluded. There were 114 detachments in 112 patients, which gave incidence of 0.46/100,000 of the population served per annum. This confirms the low incidence of this disorder found in black patients in other series. Patients were comparatively young (37.5% less than 30 years of age), men outnumbered women 2:1, and the incidence of blunt trauma was high (29.8%). Over one-third (36.6%) presented with a blind or poorly sighted opposite eye. Late presentation was common. Large posterior breaks occurred in 15.7% of detachments with severe proliferative vitreoretinopathy in 33.3%. These last characteristics accounted for the use of vitrectomy with tamponade as a primary surgical procedure in 32.5% of cases and contributed to the relatively low success rate of reattachment (72.8%). Some of the findings may be influenced by social disadvantage, but the reason for the low incidence of retinal detachment in black patients is not known. A stronger adherence of the retina to the retinal pigment epithelium in black patients is postulated. PMID- 7777966 TI - Pulmonary complications in 110 consecutive renal transplant recipients. AB - The pulmonary complications in 110 consecutive renal transplant recipients on cyclosporin and low-dose steroid immunosuppression were studied retrospectively. The pulmonary complications were: acute pulmonary oedema in 19 patients, pneumonia in 18, tuberculosis in 9, acute pulmonary embolism in 5, and lung abscess in 1. Sixty-nine patients (62.7%) had no pulmonary complications; 69% of the complications occurred in the first 4 months after the transplant. Pulmonary tuberculosis became evident later. The mean age, period of follow-up, human leucocyte antigen (HLA) B/DR mismatches, mean serum urea and serum creatinine concentrations, systolic and diastolic blood pressures, and cyclosporin dosage did not differ between the groups with no complications, infectious complications and non-infectious complications. The number of rejection episodes treated with bolus steroids was significantly higher in the infectious and non-infectious complications groups compared with the group with no complications. The incidence of pulmonary complications after renal transplantation, especially pneumonia and tuberculosis, was still high despite the use of low-dose steroids and cyclosporin. Pulmonary complications were the commonest cause of death in the first 3 years after the transplant. A high index of suspicion for pulmonary tuberculosis and pulmonary embolism in these patients is necessary. PMID- 7777967 TI - [Chronic osteomyelitis - a diagnostic dilemma]. AB - Infective skeletal lesions can mimic bony tumours. Bony lesions without periosteal reactions in adult patients with normal leucocyte counts will have a different differential diagnosis from that of children with bony lesions and a periosteal reaction. In the latter, osteomyelitis should be distinguished from Ewing's sarcoma and osteogenic sarcoma. Due to the difficult preoperative diagnosis a retrospective study was undertaken which included 14 patients with the histological diagnosis of chronic osteomyelitis but normal leucocyte count and no periosteal reaction. Radiographs showed cavities in 82%, infiltration in 12% and sclerosis in 6% of cases. All patients who underwent skeletal scintigraphy studies showed increased uptake in the lesions. Magnetic resonance showed increased signal intensity in T2 images. Ordinary radiographs are still the most valuable primary investigation for skeletal lesions. PMID- 7777968 TI - BCG vaccination status of children with tuberculous meningitis and the use of unsupervised isoniazid prophylaxis. AB - From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with local authority clinic staff. In a further 18 children a BCG scar was visible. Therefore at least 161 of the children (83%) had received BCG vaccination. As the Western Cape has also been shown to have the highest incidence of TBM in South Africa, there is concern that BCG as currently used does not have a significant protective effect against disseminated tuberculosis. Seventy-seven children (40%) were also reported to have a close household contact who had been treated for pulmonary tuberculosis within the previous 24 months. Only 17 of these children (22%), however, were prescribed prophylactic isoniazid and only 7 of these completed 3 months or more prophylaxis. PMID- 7777969 TI - Human resources for health. PMID- 7777970 TI - A prospective study of iron status in white and black pregnant women in an urban hospital. AB - Evaluation of the iron status (haemoglobin and ferritin concentrations, and percentage transferrin saturation) in a prospective study of 65 pregnant women (55 white and 10 black) revealed that adequate maternal iron stores during pregnancy cannot be maintained with prevailing dietary patterns. Although 80.6% of the patients had normal indices in the first trimester, only 12.3% were normal in the third. Significant depletion of iron stores occurred in the second trimester, but significant iron-deficient erythropoiesis only occurred in the third trimester. Despite the decline in iron status, iron deficiency anaemia was only seen in 7-8% of the patients. Even after correction for the haemodilution and increased transferrin concentrations in pregnancy, over 70% of women had depleted iron stores in the third trimester. No beneficial effect on fetal birth weights was found on withholding of maternal iron supplementation. This study clearly demonstrated that white and urban black pregnant women require iron prophylaxis to maintain iron stores. PMID- 7777971 TI - Hyperosmolar non-ketotic diabetic coma as a cause of emergency hyperglycaemic admission to Baragwanath Hospital. AB - There were 136 emergency hyperglycaemic admissions to Baragwanath Hospital over a 6-month period during 1992-1993, representing 1.2% of the total number of medical admissions; 24 (18%) patients died. Diabetic keto-acidosis (DKA) accounted for 88 (65%) admissions (mortality rate 9%) while 16 admissions (12%) were as a result of hyperosmolar non-ketotic coma (HNKC), defined as hyperglycaemia, dehydration and an altered level of consciousness with a plasma osmolality > or = 330 and an arterial pH > or = 7.30, with absent or minimal ketonuria. Of these 16 patients, 9 (56%) were known to have diabetes mellitus. Patients with HNKC were significantly older than those with DKA (P < 0.001) and other patients with nonketotic hyperglycaemia (P < 0.05). The overall mortality rate was 44%; prophylactic low-molecular-weight heparin appeared of benefit (P < 0.05). PMID- 7777972 TI - Brucellosis in childhood in the Western Cape. AB - Human brucellosis, a multisystem disease which may mimic other conditions, has a low incidence in childhood and the diagnosis may easily be missed. Over a 7-month period 9 children with brucellosis presented to the Department of Paediatrics and Child Health, Tygerberg Hospital. Six of the children had consumed unpasteurized milk. The main presenting symptoms were fever, fatigue, headache, myalgia and haematuria. Clinical signs included lymphadenopathy (3), nasopharyngitis (2), features of lower respiratory tract infection (2), splenomegaly (2) and pyrexia (1). The diagnosis was made on the basis of a positive serological titre (> 1:160) for Brucella abortus. The prozone phenomenon was encountered in 6 cases; however, the Coombs test confirmed the diagnosis in these cases. Children under 7 years were treated with co-trimoxazole and rifampicin and those over 7 years with tetracycline and rifampicin, for at least 6 weeks. No relapses were detected on follow-up. PMID- 7777974 TI - Implications of cost-cutting in the academic health complexes. PMID- 7777973 TI - MEDUNSA out of the woods. Interview by Ina van der Linde. PMID- 7777975 TI - Perinatal mortality rates. PMID- 7777976 TI - Some issues in screening, staging and treatment of oesophageal cancer. PMID- 7777977 TI - Antidepressants in patients with porphyria. PMID- 7777979 TI - Screening for cervical neoplasia. PMID- 7777980 TI - Weight reduction--what is a "good" diet? PMID- 7777981 TI - Problems caused by incorrect referrals to tuberculosis clinics. PMID- 7777982 TI - Abdominal pregnancy ending in a live birth. PMID- 7777978 TI - Abortion--some practical and ethical considerations. PMID- 7777983 TI - Familial spread of HTLV-I in KwaZulu/Natal. PMID- 7777984 TI - Misdiagnosis of Gilles de la Tourette syndrome. PMID- 7777985 TI - Fetal fibronectin in vaginal secretions--a predictor of preterm delivery? PMID- 7777986 TI - Measles--traditional Indian beliefs and practices. PMID- 7777987 TI - 'Happy feet'--a lighter side to pathology. PMID- 7777988 TI - Registering TB. PMID- 7777989 TI - Breakthrough imminent into brain damage. PMID- 7777990 TI - Doctors on abortion. PMID- 7777991 TI - Gossiping about an HIV patient can be costly. PMID- 7777992 TI - Are our health goals realistic or idealistic? PMID- 7777993 TI - Mental health and the RDP. PMID- 7777994 TI - The problems and promises of decentralisation of health services--a commentary. PMID- 7777995 TI - Towards national health insurance. PMID- 7777996 TI - Breast-milk substitutes--a South African perspective urgently needed. PMID- 7777997 TI - An integrated analysis of health facilities in the nine provinces of South Africa. AB - The development of a comprehensive national health plan must take into account an analysis of the provision and distribution of health facilities. This study collected and verified data from a number of different sources, on the number and types of hospital beds, the number of fixed clinics, and the population sizes in each of the nine new provinces of South Africa. A comprehensive database of these figures was compiled for the years 1988 and 1993. Integrated analyses were made of the distribution and types of health facilities in South Africa by using population/facility ratios. Notable disparities were found to exist between provinces in the total (public and private) distribution of hospital beds per 1,000 population, but the distribution of acute hospital beds between provinces is more even. In provinces where there is more than one medical school, there is a marked imbalance between the levels of care, with greater emphasis placed on tertiary care, at the expense of the secondary level. Given the World Health Organisation recommendation of 10,000 people per clinic, there is a shortfall in most provinces. Recommendations are made with regard to the rationalisation of academic and referral beds, and the factors to be considered in the addressing of shortages of clinic facilities. However, the limitations of a resource-based planning approach must be recognised, and it is recommended that comprehensive analyses be carried out at regional and sub-regional levels to determine the appropriate delivery of health care. PMID- 7777998 TI - Red kidney beans--to eat or not to eat? AB - The importation of dry red kidney beans (a variety of the species Phaseolus vulgaris) for cultivation or consumption in South Africa is prohibited because of their potential toxicity to humans. It has been established that the haemagglutinating lectins (e.g. phytohaemagglutinin (PHA)) in kidney beans are responsible for this toxicity. Dry bean varieties available on the South African market for human consumption as well as locally produced (for this study) and imported dry red kidney beans and imported canned red kidney beans were compared. The PHA activity and the effect of heat thereon were measured, before and after overnight soaking. The PHA activity in extracts of uncooked and incompletely cooked red kidney beans was not higher than the levels measured in 50% of the other bean varieties included in the study. These findings indicate that the toxic potentials and health risks associated with red kidney beans are similar to those of other dry beans already commercially available to South Africans. PMID- 7777999 TI - Dietary cholesterol--the role of eggs in the prudent diet. AB - The recommendation that not more than 300 mg cholesterol be consumed daily to prevent high serum cholesterol levels and coronary heart disease is often used to justify a restriction of egg intake to three or four per week. One egg contains about 200 mg of cholesterol, but eggs are also excellent and relatively inexpensive sources of essential amino acids and certain vitamins. In this paper, the place of eggs in a prudent, cholesterol-lowering diet as a substitute for other animal products, is scrutinised. The extra cholesterol, where considered as the only variable, will increase serum cholesterol levels, but the effect is relatively small. The exclusion of eggs from the diet should be weighed against deprivation of essential nutrients especially in vulnerable groups. While restriction of egg intake in westernised populations seems justifiable, the upper limit of three or four per week may not always be applicable, depending on the overall diet and lipid profile of the individual. PMID- 7778000 TI - The changing medical student population at the University of Cape Town. AB - OBJECTIVE: Since 1981, the composition of applicants and students admitted to the medical school of the University of Cape Town has changed gradually. The objective of this paper is to quantify these changes and explore possible reasons for them. DESIGN: A retrospective analysis of the actual data accumulated at each annual intake was performed and the trends determined. SETTING: Only data for the University of Cape Town medical school were evaluated. Data published by similar institutions were used for comparative purposes. RESULTS: The number of applicants has risen steadily from 1,229 in 1981 to 2,330 in 1994, so that the applicant/admission ratio now stands at 12,1:1. During this same period, the percentage of women in the class has increased, with women outnumbering men in both 1992 and 1993. In 1994, black African students comprised 24% of those admitted to the M.B. Ch.B. programme, and of these 30.4% were women. By comparison, their white colleagues constituted 45.3% of the class, 57.5% of this cohort being women. CONCLUSIONS: The composition of the 1st-year M.B. Ch.B. class at the University of Cape Town has become multiracial in character, a factor achieved partly through academic support and affirmative action. The heterogeneity of the class, particularly in respect of gender, language and socio economic factors, while appropriate and necessary, will have an impact on the university and the profession. PMID- 7778001 TI - A.R.P. Walker Lecture. Food and the gut. AB - A.R.P. Walker pioneered the research into the association between food, gut function and disease patterns in southern Africa. His attention to ways in which dietary differences can explain geographical differences in disease patterns has led to the realisation that civilisation and modern food technology can exert a strong influence on dietary practices, gut function and disease tendencies. Recognition that South African blacks have a very low incidence of colonic problems such as diverticulitis, adenomatous polyps and carcinoma drew attention to the possibility that the traditional African diet, with a high fibre content, may maintain colonic health and prevent disease in old age. This review explores some of the mechanisms that may account for these differences and also examines ways in which malnutrition alters gut function. To quote Walker's conclusions: 'There is a need, indeed a duty, for writers on nutrition to devote a portion of their space to the nutritional lessons to be learned from the past, from war-time experiences and from present day Third-World populations.' PMID- 7778002 TI - The use of DNA markers in the pre-clinical diagnosis of familial adenomatous polyposis in families in South Africa. AB - Haplotype association studies were performed in 10 unrelated South African families and 1 German immigrant family with familial adenomatous polyposis (FAP). Three DNA probes, recognising five restriction fragment length polymorphisms (RFLPs) around the gene locus for FAP on chromosome 5q, were used. The RFLP analysis was informative or partially informative in all the families studied. Five haplotypes were found to segregate with the disease locus. The predominant association of two of these haplotypes with FAP in the South African families suggests that two mutations may cause the disease in about 70% of families in this population. Meiotic recombination events were detected between the FAP gene and probe M4 (D5S6), but not probes Pi227 (D5S37) and C11p11 (D5S71). Haplotype analysis allowed the preclinical diagnosis of FAP in 5 subjects. PMID- 7778003 TI - The outcome of familial adenomatous polyposis in the absence of a polyposis registry. AB - From 1964 to 1990, 70 patients with familial adenomatous polyposis were diagnosed at an institution without a polyposis registry. Those with symptoms at diagnosis were older (mean 34 v. 24 years) and more often had large-bowel cancer (7/30 v. 1/30, 23% v. 3%). The introduction of systematic screening significantly increased the number of cases diagnosed annually, from 2,3 to 5 per year, reduced the median age at diagnosis from 29 to 21 years and increased the proportion of cases diagnosed without symptoms from 52% to 90%. A colectomy with an ileorectal anastomosis achieved a low incidence of rectal cancer at 20 years (1/15, 7%) despite imperfect follow-up and annual sigmoidoscopy in only 40%. However, bowel cancer caused at least 35% of all deaths and 62% of deaths due to a known cause. A registry which maintained a screening programme should therefore prevent most large-bowel cancers and improve the life expectancy of patients with familial adenomatous polyposis who are managed at this institution. It might also refine the current method of screening by sigmoidoscopy alone, by facilitating the use of ophthalmoscopy and blood tests for DNA markers. PMID- 7778004 TI - Non-invasive management of organic impotence. AB - OBJECTIVE: To establish the efficacy of a vacuum device (ErecAid) in the management of organic impotence. DESIGN: Cohort study; questionnaire before and after a 6-month study period. SETTING: Groote Schuur Hospital, Cape Town. PARTICIPANTS: A total of 19 men with organic impotence, 8 diabetic and 11 with previous pelvic surgery or radiotherapy. INTERVENTION: Vacuum device (ErecAid, Osbon Medical Systems). OUTCOME MEASURE: Efficacy of ErecAid. RESULTS: Six of 8 diabetics and 6 of 11 non-diabetics reported successful intercourse, while 16 of the participants would recommend the device to others. Some difficulty with the device was experienced by 11 and only 9 described an increase in self-esteem. CONCLUSION: Although some difficulties may be experienced in the use of the ErecAid, it clearly has a role to play in the management of patients with organic impotence, who ideally should be able to select their preferred form of therapy. PMID- 7778005 TI - A lumbar body support (KBS 2000) alters lumbar muscle recruitment patterns in patients with acute-upon-chronic lower back pain. AB - OBJECTIVE: To determine the effects of a locally designed lumbar body support (LBS) on integrated electromyographic (IEMG) activity of the lumbar erector spinae muscles, on heart rate and on ratings of discomfort in patients with low back pain. DESIGN: Non-randomised controlled trial. SETTING: Patients referred from general practitioners and back pain rehabilitation programmes in Cape Town. PATIENTS AND OTHER PARTICIPANTS: Ten patients with low back pain of diverse causes. Values were compared with those in 10 control subjects without low back pain. INTERVENTION: Patients and controls lay supine on (in random order) either a flat conventional mattress or a LBS placed on top of the flat mattress, for a 30-minute period (acute exposure), and every night for 2 weeks (chronic exposure). MAIN OUTCOME MEASURES: IEMG activity of the lumbar erector spinae muscles, heart rate, and perception of comfort. RESULTS: IEMG activity of the lumbar erector spinae muscles did not differ between controls and patients when lying on the LBS on top of the CM after either acute or chronic exposure. However, it was significantly greater (P < 0.05) in patients than in controls when lying on the flat mattress. Subjective ratings of discomfort and heart rates mirrored these changes and were higher in patients only when lying on the flat mattress (P < 0.05). Patients with low back pain also reported that sleeping overnight on the LBS on top of their own mattress significantly reduced discomfort ratings. CONCLUSIONS: When lying on a mattress with a flat surface, patients with chronic low back pain have higher IEMG activity of the erector spinae muscles, higher heart rates and higher subjective ratings of discomfort than do control subjects. These differences disappear when both groups use a specially designed lumbar body support placed on top of the flat surface. These preliminary studies suggest that a lumbar body support should be evaluated in the chronic management of low back pain. PMID- 7778006 TI - Hepatitis B vaccine failure in medical students. PMID- 7778007 TI - Antibody decline after hepatitis B vaccination and the effects of boosters. PMID- 7778009 TI - Retrospective analysis of a snakebite at a rural hospital in Zululand. PMID- 7778008 TI - Retrospective analysis of snakebite at a rural hospital in Zululand. PMID- 7778010 TI - Cisapride labelling change. PMID- 7778011 TI - Pseudoephedrine and imipramine for depression--grounds for caution? PMID- 7778013 TI - Traditional healers and psychiatric health care. PMID- 7778012 TI - Anabolic steroids--a contemporary perspective. PMID- 7778014 TI - Asthma 1995. PMID- 7778015 TI - [Surgical techniques in dislocations, cartilage and tendon injuries: refresher course]. PMID- 7778016 TI - [Dynamic stability of the glenohumeral joint. A biomechanical study]. AB - Stability of the glenohumeral joint with an anterior, posterior and inferior displacement force of 50 Newton was measured in a dynamic shoulder model. Controlled hydrodynamic actuator forces were applied to the deltoid muscle and to the rotator cuff in seven anatomic specimens. During elevation of the arm, the position of the humerus was measured with a six-degree-of-freedom ultrasonic sensor device. The rotational center of the humeral head was used as reference point for translation. A displacement force of 50N led to significant humeral head displacement anteriorly and posteriorly, but not inferiorly. A 50% reduction of rotator cuff forces increased anterior displacement by 46% and posterior displacement by 31%. Venting of the glenohumeral joint space and of the subacromial bursa resulted in a 50% increase of anterior displacement, a 19% increase of posterior displacement and in significant inferior displacement. This study demonstrates that, in addition to passive stabilizers and negative intraarticular pressure, rotator cuff force significantly contributes to stabilization of the glenohumeral joint during arm motion. Muscle strength and coordination should gain more emphasis in the diagnosis and treatment of shoulder instability. PMID- 7778017 TI - [Possibilities of ultrasound diagnosis in Tossy type III acromioclavicular joint injuries in comparison with loaded roentgen images]. AB - We inform about 20 patients (19 men, 1 woman) with acute acromioclavicular striking, type Tossy III, which were operated. By usual preoperative diagnostic and physical examination, x-ray standard pictures of the shoulder in two planes and x-ray panoramic picture (loaded with 10 kp and unloaded) in ap-axis we made an additional sonographic examination of the hurt shoulder. This is practiced in the commendable standardised pattern of DEGUM (German Society of Ultrasound in Medicine). After the standardised sonographic examination we focussed the acromioclavicular joint sonographically in a modified lateral vertical axis. All of the 20 examined shoulder joints belong to the stage Tossy III. In the preoperative diagnosis the difference in elevation between the lateral portion of the clavicula and the medial portion of the acromion amounts in comparison to the two shoulders (loaded versus unloaded shoulder joints) sonographically 6.2 +/- 2.6 mm (max. difference of the sides 10 mm), by the radiological examination 6.5 +/- 3.7 mm (max. difference of the sides 14 mm). The sonographical examination of the shoulder joint makes it possible to get more information about the acromioclavicular lesion, especially by an AC examination according to Tossy degree III. At present there is no possibility of substituting the standardised x ray pictures in two axes to diagnose or exclude fractures. PMID- 7778018 TI - [Results of treatment after traumatic shoulder dislocation. Thoracic abduction plaster case or Desault dressing]. AB - In 80 patients with primary traumatic shoulder dislocation treated at the Heidelberg Orthopaedic University Hospital we had a follow-up examination. We wanted to know about age and sex of the patients, the number of redislocations in correlation to time and way of fixation. We had 70% male and 30% female patients with 97.5% of anterior dislocation. The minimum age was 16 and the maximum 87 years with an average of 44 years. 48 patients had a Desault bandage for 2 weeks and 32 had a shoulder-arm plaster cast for 3 weeks. There was no difference between both ways of fixation. We also could not see any better results after more than a 3 weeks' fixation. The most important fact for redislocation is the age and activity of the patients. A young man has a very high risk of redislocation within the first year. PMID- 7778019 TI - [Fatal soccer injury as an unfortunate sequela of collision]. AB - The tragic death of a 26-year old hobby soccer player is described, who had a collision with the opposing goalie and suffered from a fracture of the left lateral process of the atlas, an extensive subarachnoid haemorrhage, tamponade of the third and fourth cerebral ventricles, bleeding into both lateral cerebral ventricles, infratentorial and supratentorial cerebral oedema. Furthermore, a survey of the literature concerning acute death in soccer is presented. PMID- 7778020 TI - [Unilateral, paramedian spinal contusion after athletic injury with complete recovery]. AB - The acute injury of the spinal column and the spinal cord asks for immediate diagnostic techniques and adequate therapeutical intensive care in order to secure the possibility of a maximum of neurologic recovery. An impact trauma of the spinal cord in sports accidents can cause an incomplete paraplegia. In some cases, morphologic lesions of the myelon cannot be detected. We present an exceptional and striking case of a 15-year old young woman who suffered from a contusio spinalis after high jump with the clinical signs of an incomplete, sensomotoric paraplegia which showed a strictly unilateral and paramedian border at the right side of her body for about two weeks. Additionally, the diagnostic possibilities of physical examination, magnetic resonance imaging, computed tomography and neurophysiologic diagnostic techniques in detecting spinal cord injuries are demonstrated. PMID- 7778021 TI - [Injuries in athletic mountain climbers in ambulatory sports medicine]. PMID- 7778022 TI - [Double-contrast arthro-CT in diagnosis of shoulder instability]. AB - Timeless and lesion-related treatment are important in the different shoulder instabilities in order to get a good functional result. Within the step-by-step programme of diagnostic possibilities the double contrast computerised arthrotomography is particularly indicated in recurrent posttraumatic and habitual dislocations, in subluxations as well as for clarification of causes of postoperative recurrence. Besides the documentation of skeletal changes (Hill Sachs-lesion, Bankart defect), double-contrast arthro-CT offers the possibility to identify detachments of the joint capsule or labral tears. Between 11/90 and 9/93 we performed 38 double contrast arthro-CTs for recurrent shoulder instabilities. 35 men and 3 women were examined. The mean age of the sportive patients were 29 years. Preoperatively we diagnosed in 21 cases a recurrent posttraumatic, in 7 cases a habitual shoulder instability. Apart from one multidirectional and three posterior instabilities we found two cases of subluxation. In the meantime 24 patients were treated with an open stabilising operation of the shoulder. The operative findings were compared with the results of double contrast arthro-CT. In a total of 38 performed arthro-CTs we found labral tears in 4 cases, 14 labral dissections, and 10 times a complete labral discontinuity. 8 of 9 labrum dissections found intraoperatively were correctly identified on CT. One dissection was not even seen retrospectively on arthro-CT. Six of nine complete labrum discontinuities were seen on arthro-CT, three described as a dissection. All capsular detachments and bony Bankart lesions found on CT were confirmed intraoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778024 TI - Colorectal carcinomas: diagnosis and preoperative staging by hydrocolonic sonography. AB - BACKGROUND: The aim of this study was to determine the sensitivity, specificity, and predictive value of hydrocolonic sonography (HS) in the detection and preoperative staging of colonic carcinomas. METHODS: One hundred four patients referred to our department for colorectal disease were examined in a prospective study with conventional transabdominal sonography followed by HS and other well established means for detection of colorectal cancer. In all diagnosed colorectal carcinomas, surgical resection and histologic examination were carried out, and the histologically confirmed tumor stage was then compared with the stage predicted by HS. RESULTS: HS staged and made a correct diagnosis of carcinoma in 39 of 40 patients, with a sensitivity of 97.5% and a specificity of 98%. Positive predictability was 97.5% and negative predictability 98%. In the evaluation of cancer depth invasion, HS staging was correct in all but one case, in which a T3 tumor was incorrectly judged to be T2. In the assessment of the presence or absence of peritumor metastatic lymph nodes, HS had a sensitivity of 50% and a specificity of 100%. CONCLUSIONS: HS allows the diagnosis and preoperative staging of colorectal carcinomas with high sensitivity, specificity, and predictive value. We highly recommend its preoperative use because of its definitive influence on surgical approach. PMID- 7778023 TI - Prognostic significance of three novel biologic factors in a clinical trial of adjuvant therapy for node-negative breast cancer. AB - BACKGROUND: Five products of human breast carcinoma cells, including membrane associated phospholipase A2 (M-PLA2), polymorphonuclear leukocyte elastase (PMN E), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and endothelin-1 (ET-1), have been implicated in the processes of tumor cell invasion and metastasis in human breast carcinoma. However, the prognostic significance of these factors has not been assessed previously in node negative breast carcinoma, in which adjuvant treatment is dependent on risk stratification. METHODS: The five products of breast carcinoma cells were measured in 184 patients with node-negative breast carcinoma who were enrolled in the Kumamoto Adjuvant Chemo-Endocrine Therapy for Breast Cancer prospective randomized trial, and the predictive values of these factors for relapse-free and overall survival were evaluated. RESULTS: M-PLA2, PMN-E, and t-PA were found to be significant independent predictors of relapse-free and overall survival, whereas u-PA and ET-1 were not independently predictive. Further statistical analyses showed that the predictive powers of M-PLA2, PMN-E, and t-PA were additive. A combination of these three factors identified a group of patients (approximately 50% of those who manifested node-negative breast carcinoma) with a favorable prognosis, regardless of the administration of adjuvant therapy. CONCLUSIONS: This study identified three biologic factors that are valuable predictors of survival in node-negative breast carcinoma. A combination of these biologic factors may allow identification of low-risk patients who could be spared adjuvant therapy. PMID- 7778025 TI - Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion. AB - BACKGROUND: The pattern of tumor spread, vis-a-vis nodal involvement and invasion of the extrapancreatic plexus (Plx), has not been thoroughly described for carcinoma of the pancreatic head area. METHODS: From 1973 to 1991, 110 patients (49 with carcinoma of the pancreatic head [Ph], 29 with distal bile duct cancer [Bi], and 32 with carcinoma of the papilla of Vater [Pv]) underwent pancreatectomy at Kanazawa University Hospital. Nodal involvement and Plx invasion were precisely evaluated by histopathologic examination. RESULTS: Thirty seven (76%) of the 49 patients with Ph, 20 (69%) of the 29 with Bi, and 14 (44%) of the 32 with Pv had nodal involvement. The lymph nodes most commonly involved for Ph were the posterior pancreaticoduodenal lymph nodes (numbers 13a [superior] and 13b [inferior]), the superior mesenteric lymph nodes (number 14), the paraaortic lymph nodes (number 16), and the anterior pancreaticoduodenal lymph nodes (number 17) (13a, 51%; 13b, 47%; 14, 36.7%; 16, 18.4%; 17a, 33%; 17b, 22%). In patients with Bi, lymph nodes around the hepatoduodenal ligament (number 12) and lymph nodes numbers 13a and 14 were most commonly involved (12, 27.6%; 13a, 51.7%; 14, 34.5%). In patients with Pv, lymph node numbers 13b and 14 were most frequently involved (13b, 34.4%; 14, 15.6%). No significant correlation was noted between the tumor size and nodal involvement in these three lesions. Nodal involvement was an important prognostic factor for carcinoma of the pancreatic head area. Plx invasion in these three carcinomas was observed in 61% of patients with Ph, 29% of patients with Bi, and 3% of patients with Pv. CONCLUSIONS: Nodal involvement and Plx invasion differed significantly among carcinomas of the pancreatic head area. We believe that nodal dissection of at least group number 14 is needed for Ph, Bi, and Pv cancers. In addition, dissection of lymph nodes of number 16 and the Plx around the superior mesenteric artery and celiac axis are needed in Ph cancer. Plx dissection of the first portion of plexus pancreaticus capitalis is needed in Bi cancer. PMID- 7778026 TI - Continuous hepatic arterial infusion of 5-fluorouracil for unresectable colorectal liver metastases: phase II study. AB - BACKGROUND: Although hepatic arterial infusion therapy (HAIT) with 5-fluoro-2' deoxyuridine for colorectal liver metastases yielded a good response, the treatment may be limited by hepatic toxicities. This study was designed to evaluate HAIT by using 5-fluorouracil (5-FU), with the expectation of a good response with little hepatic toxicities. METHODS: HAIT was begun at a dose of 360 mg/m2 of 5-FU for 7 days by using an extracorporeal infusion pump, followed by 180 mg/m2 of 5-FU for 21 days. After a 7-day interval, 180 mg/m2 of 5-FU was infused for 7 days; this 7-day infusion/7-day no infusion cycle was repeated. RESULTS: Fifty-three of the 68 patients who were referred to this study were evaluable. Complete response was observed in two patients and partial response in 25 (response rate of 50.9%), with a median survival time of 11 months: 18 months for 27 responders and 7 months for 26 nonresponders. Gastrointestinal complications were observed in 18 patients: abdominal pain in nine, vomiting in five, and bleeding in four. No hepatobiliary or hematologic toxicities occurred. Infusion-related complications occurred in 20 patients. CONCLUSIONS: HAIT with 5 FU may provide an effect similar to HAIT with fluoro-2' deoxyuridine but without hepatobiliary complications. PMID- 7778027 TI - Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. AB - BACKGROUND: Preoperative localization of gastrinomas by current imaging techniques such as computed tomography (CT) scan and angiography is still difficult because of the small size of tumor(s) in most patients undergoing operation. This study evaluated the diagnostic value of endoscopic ultrasonography. METHODS: Twenty-two patients presenting with Zollinger-Ellison syndrome underwent exploratory laparotomy after preoperative attempts to identify the gastrinoma(s) by CT scan, upper gastrointestinal endoscopy, and endoscopic ultrasonography. Surgery included intraoperative ultrasonography and duodenal transillumination in all cases. The sensitivity and specificity of imaging techniques were then evaluated. RESULTS: At least one tumor was found in 19 patients (four had two tumors and one had multiple tumors). Duodenal, lymph node, and pancreatic gastrinomas were found in 42%, 38%, and 17% of the patients, respectively. Sensitivity of endoscopic ultrasonography was 50% for duodenal wall tumors (conventional endoscopy, 40%), 75% for pancreatic tumors (CT scan, 25%), and 62.5% for tumoral lymph nodes (CT scan, 0%). The specificity of all techniques was excellent. Correct diagnosis was made by endoscopic ultrasonography alone in 41% of the patients. The combination of conventional endoscopy and endoscopic ultrasonography provided correct diagnosis in 60% of the patients. CONCLUSIONS: Endoscopic ultrasonography should be considered as a first choice imaging technique for preoperative detection of gastrinomas. Although small duodenal gastrinomas are still obviously difficult to detect, an accurate exploration of the pancreatic area was provided by this technique. PMID- 7778028 TI - Tube jejunostomy in liver transplant recipients. AB - BACKGROUND: Nutritional support after liver transplantation most often uses intravenous hyperalimentation followed by nasoduodenal tubes until adequate intake is achieved. Because of difficulties with nasoduodenal tubes, we place jejunostomy tubes (j-tube) at the time of the transplantation, allowing immediate postoperative enteral nutrition. This review analyzes the complications of this procedure in transplant recipients. METHODS: J-tubes were placed in 108 of 119 adults who underwent liver transplantation between October 1989 and June 6, 1994. These patients were retrospectively reviewed for the type and frequency of j-tube related complications. J-tube feeds with a semielemental formula were started within 24 to 48 hours after transplantation. RESULTS: Eighteen complications occurred in 16 patients. Six were mechanical obstructions of the j-tube because of kinking by the fascia. Six exploratory laparotomies were required, two each for infection, small bowel obstruction, or catheter displacement. Four other infections were treated by local incision and drainage or percutaneous drainage. One tube required surgical removal in the operating room. CONCLUSIONS: Tube jejunostomies can be safely placed at the time of liver transplantation with a low risk of serious complications. We recommend the routine use of j-tubes in patients receiving a liver transplant for the immediate posttransplantation institution of enteral nutrition. PMID- 7778029 TI - Protective effects of a novel 32-amino acid C-terminal fragment of CAP18 in endotoxemic pigs. AB - BACKGROUND: Cationic antimicrobial protein of 18 kd (CAP18) is a neutrophil derived peptide that binds lipopolysaccharide (LPS) with high affinity. We hypothesized that CAP18(106-137), a novel synthetic 32-amino acid C-terminal fragment of CAP18, would neutralize the physiologic derangements induced by LPS in anesthetized swine. METHODS: Pigs were randomly allocated into three groups. Those in the LPS group (n = 6) were infused with LPS (3 micrograms/kg/hr for 4 hours). Pigs in the LPS/CAP18 group (n = 6) were challenged with LPS (3 micrograms/kg/hr for 4 hours) and also treated with CAP18(106-137) (4 mg/kg/hr for 4 hours). Pigs in the RL group (n = 4) received neither LPS nor CAP18(106 137). RESULTS: Treatment with CAP18(106-137) blocked LPS-induced increases in plasma levels of 6-keto-prostaglandin F1 alpha and tumor necrosis factor-alpha and prevented LPS-induced changes in cardiac output, arterial PO2, phagocyte activation, and peripheral leukocyte count. Changes in circulating concentrations of thromboxane B2, mean pulmonary artery pressure, and dynamic pulmonary compliance were attenuated in the LPS/CAP18 group. CONCLUSIONS: Treatment with CAP18(106-137) neutralizes many of the deleterious effects of LPS in pigs. PMID- 7778030 TI - Effects of perfluorocarbon exchange transfusion on reducing myocardial infarct size in a primate model of ischemia-reperfusion injury: a prospective, randomized study. AB - BACKGROUND: This study was undertaken to test the hypothesis that perfluorocarbons were able to reduce myocardial infarct size in a baboon model of ischemia-reperfusion injury. Exchange transfusion of perfluorocarbons has been shown to reduce myocardial infarct size in the dog, who, unlike the baboon, has an extensive collateral circulation. METHODS: After 15 minutes of occlusion of the left anterior descending coronary artery, 14 baboons were bled to attain a hematocrit of 24% to 26% and were simultaneously transfused, six with Fluosol-DA 20% emulsion and eight with FC-43 emulsion. After 2 hours of ligation, the coronary arteries were reperfused. Baboons were killed 24 hours after ligation, and the hearts were excised. Microvascular dye was infused into the coronary artery to delineate its perfusion bed. Ratios of the mean volume of infarct to the mean volume of perfusion bed were calculated and compared by use of planimetry. A similar protocol was followed in two other groups of baboons except that lactated Ringer's solution was infused into six of them, whereas eight had no exchange transfusions. RESULTS: The ratios of the mean volume of infarct to the mean volume of perfusion bed of the four groups were as follows: Fluosol-DA, 38.1% +/- 7.5%; FC-43, 37.7% +/- 8.3%; lactated Ringer's, 46.9% +/- 10.5%; controls, 65.6% +/- 6.9%. Statistical significance was reached when comparing both perfluorocarbon-treated groups with the controls (p < 0.05 for both groups) but not significant when comparing them with the Ringer's lactate-treated group. CONCLUSIONS: Results suggest that the beneficial effects of exchange transfusion with the perfluorocarbons may be primarily due to hemodilution. PMID- 7778032 TI - Three-dimensional pressure image and muscular structure of the human lower esophageal sphincter. AB - BACKGROUND: The structural equivalent to the manometric high pressure zone separating the stomach from the esophagus is still a matter of dispute. We compared the three-dimensional (3D) manometric pressure image with muscular thickness and architecture at the human gastroesophageal junction. METHODS: Three dimensional manometric images were obtained in 25 volunteers by using a stepwise pullback technique of a catheter with eight radially oriented pressure transducers. Muscle thickness was measured in four radial directions at 10 levels between the midesophagus and stomach in 37 specimens obtained from organ donors. Muscular architecture was assessed in specimens from 10 organ donors and 12 human cadavers and was related to muscle thickness. RESULTS: Manometric 3D images of the lower esophageal high pressure zone showed a marked radial and longitudinal asymmetry. Radial pressures peaked at the respiratory inversion point and were highest toward the left posterior direction. Anatomic evaluation showed an asymmetric thickening of the muscular layer at the gastroesophageal junction that mirrored the manometric image. Muscle thickness was highest toward the greater curvature side corresponding to the gastric "sling" fibers and toward the lesser curvature corresponding to the semicircular "clasp" fibers. CONCLUSIONS: The human lower esophageal sphincter is not a muscular ring. Rather, the perfect match between the manometric pressures and the arrangement of muscular structures at the gastroesophageal junction indicates that the gastric sling fibers and the semicircular clasps are the anatomic correlate of the manometric lower esophageal sphincter in human beings. PMID- 7778031 TI - Right or left trisegment portal vein embolization before hepatic trisegmentectomy for hilar bile duct carcinoma. AB - BACKGROUND: Percutaneous transhepatic embolization of the right portal vein plus the left medial portal branch (R3-PE) and the left portal vein plus the right anterior portal branch (L3-PE) is not well described. METHODS: Four patients with far advanced carcinoma of the hepatic hilus underwent R3-PE (n = 1) or L3-PE (n = 3) as preoperative management for right hepatic trisegmentectomy or left hepatic trisegmentectomy. The portal vein embolization was performed with the ipsilateral approach through the right anterior portal branch. RESULTS: In all patients the embolizations were successful without complications. Volumetric study with computed tomography showed sufficient hypertrophy of the nonembolized hepatic segments. Three of the four patients eventually underwent trisegmentectomy. The postoperative courses in two of the patients were uneventful. The remaining patient suffered from posthepatectomy liver failure but recovered. CONCLUSIONS: R3-PE or L3-PE is advisable as preoperative management for trisegmentectomy and appears effective for increasing the safety of the operation. This embolization is achievable only through the ipsilateral approach. PMID- 7778033 TI - Synergism of acid and duodenogastroesophageal reflux in complicated Barrett's esophagus. AB - BACKGROUND: The role of acid and duodenogastroesophageal reflux (DGER) in the development of complications in Barrett's esophagus is controversial. We characterized the esophageal reflux constituents in patients with and without complications of Barrett's esophagus. METHODS: Using a new fiber-optic system we studied 12 normal subjects (six male; mean age, 46 years) and 20 patients with Barrett's esophagus (17 male; mean age, 58 years), nine with uncomplicated (seven male; mean age, 55 years) and 11 with complicated Barrett's esophagus (seven with stricture, two with ulcer, and two with dysplasia; 10 male; mean age, 61 years). Fasting gastric bile acid concentrations were measured. Twenty-four-hour ambulatory acid and bilirubin measurements were obtained with the fiber-optic system by using a glass electrode and fiber-optic sensor. The data were then analyzed for percent total time pH < 4 and > 7 and bilirubin absorbance > 0.14%. RESULTS: Percent times pH < 4, bilirubin absorbance > 0.14%, and fasting gastric bile acid concentrations were significantly greater in patients with complicated Barrett's esophagus compared with patients with uncomplicated Barrett's esophagus with both being higher than the controls. Acid reflux paralleled bile reflux in the two Barrett's esophagus groups (r = 0.44, p < 0.05), but percent time pH > 7 did not differentiate between the two groups. CONCLUSIONS: (1) Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus. (2) Complications in Barrett's esophagus may be due to synergism between acid and bile rather than either constituent alone. PMID- 7778034 TI - Plasma cholecystokinin levels and gallbladder volumes after proctocolectomy with ileal pouch-anal anastomosis. AB - BACKGROUND: The colon and rectum contain regulatory peptides in mucosal endocrine cells, which suggests a hormonal role. In animal studies colectomy leads to increased plasma levels of cholecystokinin. Little is known about the effects of proctocolectomy with ileal pouch-anal anastomosis on the release of cholecystokinin in human beings. Therefore we studied the effects of this procedure on fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels and gallbladder volumes. METHODS: Ten patients who had undergone proctocolectomy with ileal pouch-anal anastomosis and 12 healthy volunteers participated in the study. Fasting and postprandial plasma cholecystokinin levels and gallbladder volumes were studied for 3 hours at 15 minute intervals. In a second experiment plasma cholecystokinin levels were measured before and during intravenous administration of bombesin in six patients with ileal pouch and five healthy volunteers. RESULTS: Fasting plasma cholecystokinin levels were higher (p < 0.05) in patients with ileal pouch-anal anastomosis (2.6 +/- 0.3 pmol/L) compared with controls (1.7 +/- 0.2 pmol/L). Integrated postprandial plasma cholecystokinin levels were also distinctly higher (p < 0.01) in patients (978 +/- 126 pmol/L.180 min) than in controls (588 +/- 60 pmol/L.180 min). Mean fasting gallbladder volume was significantly (p < 0.01) decreased in patients with ileal pouch-anal anastomosis (18 +/- 2 ml) compared with controls (28 +/- 2 ml). Postprandial gallbladder emptying as measured by percentage change was similar in both groups. After infusion of bombesin, integrated plasma cholecystokinin responses were higher (p < 0.05) in patients (161 +/- 20 pmol/L.20 min) than in controls (90 +/- 12 pmol/L.20 min). CONCLUSIONS: Fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels are elevated in patients with ileal pouch-anal anastomosis compared with controls. Fasting gallbladder volume is decreased after ileal pouch anal anastomosis. These findings suggest that the colon contains a factor that inhibits the release of cholecystokinin. PMID- 7778035 TI - Successful intraarterial fragmentation and urokinase therapy in superior mesenteric artery embolisms. PMID- 7778036 TI - Extended left hepatic trisegmentectomy with resection of main right hepatic vein and preservation of middle and inferior right hepatic veins. PMID- 7778037 TI - Young adults with hernias. PMID- 7778038 TI - Treatment of liver cancers with complete hepatic venous isolation and extracorporeal chemofiltration. PMID- 7778040 TI - 34th Annual meeting of the Japanese Teratology Society. Kochi, Japan, July 14-16, 1994. Abstracts. PMID- 7778041 TI - Hypothesis: the pathogenesis of the birth defects reported in cvs-exposed infants. PMID- 7778039 TI - Wound and port site recurrence. PMID- 7778042 TI - Early events following maternal exposure to 5-fluorouracil lead to dysmorphology in cultured embryonic tissues. AB - The chemotherapeutic agent 5-fluorouracil (5-FU) is teratogenic in a number of species, yet the mechanism(s) of its developmental toxicity are not fully understood. Administration of 5-FU to the pregnant CD rat on day 14 of gestation results in dose-dependent growth retardation and numerous malformations in near term fetuses, including hindlimb defects and cleft palate. Following treatment, a number of rapid biochemical and cellular alterations are detectable in embryonic hindlimbs, craniofacial and other tissues, which include thymidylate synthetase (TS) inhibition and altered cell cycle progression. In order to assess the importance of these early events in 5-FU-induced dysmorphogenesis, embryonic mid facial tissues and hindlimbs were dissected 3 or 6 hr after administration of 5 FU to the dam and placed in explant culture. After 5 days in culture, craniofacial explants were evaluated morphologically for palatal closure and growth was assessed by measuring total protein and DNA content. Hindlimb explants were stained for cartilage using alcian blue to evaluate development of the digits. Craniofacial explants cultured at either 3 or 6 hr after exposure exhibited dose-dependent growth retardation and defects of palatal fusion at the end of the culture period. Deficits in protein and DNA content were similar to those in craniofacial tissues that continued to develop in utero after treatment, although morphological defects in cultured explants did not correlate well with the incidence of cleft palate in vivo. Dose-dependent deficits in metatarsal and phalanx development were observed in hindlimb explants dissected either 3 or 6 hr after maternal treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778043 TI - Developmental toxicity of the HMG-CoA reductase inhibitor, atorvastatin, in rats and rabbits. AB - The developmental toxicity of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, was investigated in pregnant rats and rabbits given daily oral doses during organogenesis. Rats received 0, 10, 100, or 300 mg/kg on days 6-15 of gestation, and rabbits received 0, 10, 50, or 100 mg/kg on days 6-18 of gestation. Maternal and fetal parameters were evaluated on day 20 (rats) or 29 (rabbits) of gestation. Live fetuses were examined for external, visceral, and skeletal malformations and variations. At 300 mg/kg in rats, 1 treatment-related death occurred on day 12 of gestation, and maternal body weight gain and food consumption were decreased during treatment (43% and 23%, respectively). In addition, 1 animal at 300 mg/kg had total litter resorption. Increased postimplantation loss (not statistically significant) and slightly decreased fetal body weight (statistically significant only in males) were also observed at 300 mg/kg. There were no significant differences between treated and control groups in the incidence of fetal malformations or variations. No maternal or developmental toxicity was observed in rats at 10 or 100 mg/kg. In rabbits, marked maternal toxicity (7 deaths, body weight loss during and after treatment, and decreased food consumption) and abortion occurred at 100 mg/kg. At 50 mg/kg, maternal toxicity (2 deaths and 72% body weight gain suppression) and abortion also occurred. There were no treatment-related effects on live litter size or sex ratio. At 50 and 100 mg/kg, nonstatistically significant increases in postimplantation loss and decreases in gravid uterine weight were observed, and at 100 mg/kg, decreases in fetal body weight were observed relative to controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778045 TI - Teratogen update: angiotensin-converting enzyme inhibitors. AB - Occasionally there is a drug whose record in pregnancy is so frequently associated with adverse outcome of so specific a pattern that it becomes clear that its use must be restricted before scientific proof from epidemiological studies is obtained. I believe this to be the case with the drug class of ACEIs. There are mammalian models suggesting substantial fetotoxicity in a dose-related fashion. There is a strong and consistent pattern to the reported cases of ACEI related adverse outcomes: the syndrome of oligohydramnios-anuria, neonatal hypotension, renal dysplasia, and hypocalvaria is too specific in association with the use of these drugs to be ignored. There is a very plausible biologic mechanism to explain the relationship. The features of ACEI fetopathy suggest that the underlying pathogenetic mechanism is fetal hypotension, which may also result from other exposures. Thus, while the fetopathy may not be truly specific to ACEIs, they are particularly liable to produce adverse fetal renal effects with their sequels (anuria-oligohydramnios, pulmonary hypoplasia, growth restriction) and hypocalvaria. PMID- 7778046 TI - Board trouble. What activities attract the attention of the Texas State Board of Medical Examiners. AB - Every year about 45,000 Texas physicians dutifully get out their checkbooks and send off a few hundred dollars to this state institution. Besides taking the test for their licenses in the first place, mailing that yearly check marks the extent to which most Texas physicians ever come into contact with the Texas State Board of Medical Examiners (TSBME). But for a number of physicians each year, a brush with TSBME is akin to facing a medical malpractice lawsuit, only the board has the power to take away their licenses. And under the Medical Practice Act of Texas, there is no statute of limitations for bringing accusations against a physician for possible violations. PMID- 7778044 TI - Growth profiles of human autosomal trisomies at midgestation. AB - Somatic and visceral growth profiles of midgestation human fetuses with trisomy 21, 18, or 13 demonstrate that each disorder has a characteristic pattern of growth aberration. The most striking deviations are short limbs in trisomy 21, subnormal adrenal and lung weights in trisomy 18, and supranormal spleen and kidney weights in trisomy 13. PMID- 7778047 TI - 'I fell down the stairs.' Physicians can help by learning to recognize the signs of domestic violence. AB - The baby lay on the examining table, his elbow swollen to grotesque proportions like some jumbo orange had sprouted from his tiny arm. And Diana Fite, MD, remembers wondering how the 1-year-old child could have sustained such an awful fracture from just falling out of bed. In 2 years as an emergency physician, she'd seen her share of injuries from out-of-bed falls--usually split lips, minor head lacerations, or, at worst, fractured clavicles. But nothing like what this baby had. PMID- 7778048 TI - Survival tactics. 75 strategies for success in the changing medical marketplace. PMID- 7778049 TI - Why Johnny hates science. Poor student performance worries physicians, educators. AB - Imagine medical schools faced with applicants who know or care little about science because they are the products of an educational system that did not motivate them to take an interest in the subject. Now imagine what kind of physicians they would be if they managed to get into medical school and graduate. John Burnside, MD, has imagined it, and it scares him. PMID- 7778050 TI - Prevention is key to combating stroke. PMID- 7778051 TI - What's new in stroke? AB - More than 30,000 strokes occur each year in Texas, even though most strokes can be prevented by currently available and well-tolerated therapies. Antiplatelet therapy with aspirin or ticlopidine reduces stroke by about 25% in many patients with transient ischemic attack or initial stroke. Warfarin should not be used routinely for primary cerebrovascular disease but is useful to prevent cardioembolic stroke. Carotid endarterectomy is highly beneficial for patients with symptomatic, high-grade carotid stenosis, but its value for lesser degrees of symptomatic carotid plaque and for asymptomatic stenosis is less clear. Patients with nonvalvular atrial fibrillation have a substantial risk for stroke; most should be treated with warfarin. Risk-factor management (eg, control of hypertension, cessation of smoking, and treatment of hyperlipidemia) is as important as antithrombotic or surgical therapies for most patients with threatened stroke. Treating isolated systolic hypertension in elderly patients reduces stroke risk. Determining the cause of threatened stroke strongly influences preventive management. The tools are at hand to prevent most strokes; the challenge remains to apply them optimally. PMID- 7778052 TI - An overview of tick-borne relapsing fever with emphasis on outbreaks in Texas. AB - Tick-borne relapsing fever (TBRF), a disease of humans and other animals, has been recognized in North America since early in this century. Caused by Borrelia spirochetes, TBRF is transmitted by softshelled Ornithodoros ticks, which may also act as reservoirs for the etiologic agents. Initial symptoms include sudden onset of fever, chills, headache, arthralgias, and myalgias. Persons with TBRF may suffer several febrile episodes or relapses unless they are diagnosed and treated promptly because TBRF spirochetes are able to alter their outer surface proteins and, thus, escape the infected host's immune response. Laboratory diagnosis is made by detecting spirochetes in peripheral blood specimens or by inoculating laboratory mice with blood collected during febrile episodes. In the 1930s and '40s, TBRF was reported commonly in Texas. More recently, fewer cases have been reported, although 13 cases were confirmed between 1990 and the first half of 1994. PMID- 7778053 TI - Pulling in the reins. TMA-backed legislation seeks to halt managed care free-for all. PMID- 7778054 TI - A memorial to Gwendolyn J. Stewart, Ph.D. (November 12, 1926--August 22, 1994). PMID- 7778055 TI - Studies on in vitro effect of picotamide on human platelet aggregation in platelet-rich plasma and whole blood. AB - Picotamide is a new antiaggregating agent influencing the platelet prostaglandin pathway through an inhibition of thromboxane A2 (TXA2) synthesis and a competitive antagonism of platelet TXA2 receptors. In the present study, we investigated the in vitro effect of this drug on human platelet aggregation induced by different agents (adenosine 5'-diphosphate [ADP], collagen, Na arachidonate) both in platelet-rich plasma (PRP; Born's method) and whole blood (WB; impedance method). For each aggregating agent, ED50 value (agonist concentration necessary to induce a maximal aggregation of 50%) was determined in control samples and following addition of different picotamide concentrations on the basis of dose-response curves. Picotamide decreased the response to each aggregating agent in both WB and PRP samples. In WB, 25 microM picotamide was able to induce a highly significant enhancement of ED50 values for ADP (from 6.6 +/- 1 microM to 12.7 +/- 1.7 microM, p < 0.01), Na arachidonate (from 740 +/- 240 microM to 1,080 +/- 280 microM, p < 0.01) and collagen (from 2.4 +/- 0.3 micrograms/ml to 3.8 +/- 0.15 micrograms/ml, p < 0.01). In PRP, the same picotamide concentration significantly enhanced ED50 for each aggregating agent (from 2.0 +/- 0.1 microM to 3.1 +/- 0.3 microM for ADP, p < 0.01; from 960 +/- 80 microM to 1,850 +/- 260 microM for Na arachidonate, p < 0.001; from 3.0 +/- 0.3 microgram/ml to 5.0 +/- 0.8 micrograms/ml for collagen, p < 0.01). Present results show that picotamide effect on platelet response is present also in WB. Data might support the use of picotamide as antiaggregating agent in vascular diseases. PMID- 7778057 TI - Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor. AB - Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6-150 micrograms/min) and 60 age- and sex matched controls with normoalbuminuria (UAER < 6.6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors: plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2-8.3) vs. 7.2 (6.9-7.5) mumol/l; p < 0.1). Neither did any of the haemostatic factors correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease. PMID- 7778056 TI - Effects of thromboxane A2 synthase inhibitors (CV-4151 and ozagrel), aspirin, and ticlopidine on the thrombosis caused by endothelial cell injury. AB - The antiplatelet and antithrombotic effects of CV-4151 (isbogrel), a potent selective thromboxane A2 (TXA2) synthase inhibitor, were compared with those of ozagrel (OKY-046), aspirin, and ticlopidine in rats. Two hours after oral administration, CV-4151, ozagrel and aspirin inhibited blood TXA2 generation with ID50 values of 0.04, 0.3 and 6.4 mg/kg, respectively. These values were similar to the oral ID50 values of CV-4151 (0.06 mg/kg), ozagrel (0.92 mg/kg) and aspirin (7.0 mg/kg) for arachidonic acid (AA)-induced platelet aggregation ex vivo. Two hours after p.o. administration, CV-4151 and ozagrel inhibited femoral vein platelet-rich thrombosis caused by endothelial injury with ID50 values of 2.46 and 13.7 mg/kg, respectively. However, aspirin (100 mg/kg, p.o.) only slightly inhibited the thrombosis. Ticlopidine (300 mg/kg, p.o.) slightly but significantly inhibited AA-induced and ADP-induced platelet aggregation, however, it potently inhibited the thrombosis. CV-4151 and ozagrel given by i.v. injection showed therapeutic effects on the thrombosis with ED50 values of 0.026 and 0.066 mg/kg, respectively. These values were similar to the i.v. ED50 values of CV-4151 (0.0056 mg/kg) and ozagrel (0.042 mg/kg) for blood TXA2 generation. However, aspirin (30 mg/kg, i.v.) only moderately reduced the thrombosis. CV-4151 (> 0.3 mg/kg, p.o.), ozagrel (> 3 mg/kg, p.o.) and ticlopidine (300 mg/kg, p.o.) all significantly prolonged tail bleeding time. Aspirin (100 mg/kg, p.o.) tended to prolong the bleeding time. The antiplatelet and antithrombotic effects of CV-4151 are more potent than those of ozagrel, aspirin and ticlopidine in rats. CV-4151 may therefore be a useful drug for the treatment of thrombotic diseases. PMID- 7778058 TI - Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells. AB - The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF alpha) have been demonstrated to modulate the expression of fibrinolytic factors in cultured endothelial cells. In the present study the expression of tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) antigen in conditioned medium from cultured human umbilical vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was investigated under basal conditions and after stimulation with LPS, TNF alpha, interferon gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF alpha increased the expression of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA response differed between the two cell types. The effects of TNF alpha were modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF alpha was reduced by IFN-gamma. In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma. These effects of IFN-gamma represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction. PMID- 7778059 TI - LPS induced procoagulant activity and plasminogen activator activity in mononuclear cells from persons with high or low levels of HDL lipoprotein. AB - We have examined spontaneous and lipopolysaccharide (LPS) induced procoagulant activity (PCA) and plasminogen activator activity (PA) in peripheral blood mononuclear cells (PBMC) from ten persons with high, and ten persons with low levels of serum high-density lipoprotein (HDL). PBMC were incubated +/- 100 ng LPS/ml up to 160 h. Additionally, we have measured the release of urokinase (uPA), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI 1) and plasminogen activator inhibitor 2 (PAI-2) into the cell culture media. Spontaneous PA was significantly higher in PBMC from persons with low HDL, combined with lower release of uPA to the media and higher uPA-receptor (uPA-R) bound uPA on PBMC. Upon stimulation with LPS, PCA and released PAI-2 increased sharply, while PA and released uPA declined. These changes were not significantly different between the two groups. tPA and PAI-1 were not detected in cell lysates or in cell culture media. CONCLUSIONS: 1) LPS sharply stimulated PBMC PCA (similar in both groups). 2) PBMC from persons with low HDL showed higher spontaneous PA, due to higher uPA-R bound uPA, probably of importance in cell migration during the early events of atherosclerosis. PMID- 7778060 TI - Platelet aggregation monitored in a 96 well microplate reader is useful for evaluation of platelet agonists and antagonists. AB - Optimal conditions for a method to simultaneously measure aggregation in 96 samples using a microplate reader were developed. The temperature of the assay was set at 25 degrees C, the optimal platelet concentration range was determined to be from 1-3 x 10(8) per mL, the assay volume was determined to be best at 100 microL and an agitation rate of setting #5 on the vortex was found to yield the most reliable aggregation response. After these initial assay parameters were established, EC50 values for standard platelet agonists including ADP, thrombin, collagen and thrombin receptor activating peptides were determined using the plate assay and compared to those obtained by measuring light transmittance in an aggregometer. The results were quantitatively similar, and qualitatively the shapes of the aggregations as monitored by both methods were characteristic of those expected for each agonist. The use of this assay was then extended to quantitate the inhibition of aggregation by antagonists of the fibrinogen receptor as well as by an inactive thrombin receptor peptide and by antibodies against the thrombin receptor. This method provided useful data for characterization of both platelet agonists and antagonists and should be useful for future platelet aggregation studies. PMID- 7778061 TI - Evaluation of plasma 11-dehydro-thromboxane B2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals. AB - Since thromboxane (TX) B2 is not a reliable indicator of TXA2 generation in vivo, because of artifactual TXA2 generation during blood collection, we tested the feasibility of replacing TXB2 with 11-dehydro (dh)-TXB2 as the indicator. Plasma levels of TXB2 and 11-dh-TXB2 were measured after i.v. administration of TXB2 to rabbits, guinea pigs, rats, dogs and a monkey, and after i.v. infusion of collagen in rabbits. In the rabbits and dogs, 2,3-dinor-TXB2 levels were also measured. After intravenous injection of TXB2 (10 micrograms/kg) in rabbits, the ratio of the area under the curve (AUC) of 11-dh-TXB2 to that of TXB2 (1.94) was far higher than the AUC ratio between 2,3-dinor-TXB2 and TXB2 (0.42). When endogenous TXA2 was generated by infusion of collagen (2 mg/kg/5 min), the plasma level of 11-dh-TXB2 was significantly increased, and had a longer half-life than TXB2. In the guinea pigs, rats and monkey, the peak plasma levels of 11-dh-TXB2 were significantly increased after injection of TXB2 (10 micrograms/kg, i.v.), whereas the AUC ratios of 11-dh-TXB2/TXB2 were less than one fourth of that in rabbits. No significant increase in 11-dh-TXB2 was observed after TXB2 injection (10 micrograms/kg) in dogs, but the 2,3-dinor-TXB2 level rose significantly, its AUC ratio to TXB2 being 0.29, comparable with that in rabbits. The order of the 11-dh-TXB2/TXB2 AUC ratios was: rabbits > guinea pigs > monkey > rats >> dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778062 TI - Thrombolysis with tissue plasminogen activator (tPA) is temperature dependent. AB - Thrombolysis with tissue plasminogen activator (tPA) and hypothermia are two potential treatment modalities for acute ischemic stroke. Many investigators are studying these modalities both in the laboratory and in clinical trials. Because these modalities each appear to show benefit in animal models, there is considerable interest in studying combined therapy with both thrombolysis and hypothermia. However, it is known that alterations in the coagulation system can occur with decreased body temperature. Clinicians have frequently observed bleeding problems when patients are subjected to hypothermia for a variety of reasons. Hypothermia induced coagulopathy has been attributed to a variety of factors. Hypothermia can cause platelet dysfunction, inhibition of clotting factors, increased fibrinolysis and endogenous production of a heparin-like factor. Groups who studied fibrinolysis and temperature, however, found the opposite to be the case. Clot lysis studies with streptokinase showed increased fibrinolysis at higher temperatures. Data by Mumme suggested that the peak fibrinolytic activity of streptokinase was at 40 degrees C, but at 43 degrees C fibrinolytic activity was decreased. Rijken et al studied plasminogen activation with tissue plasminogen activator (tPA), urokinase and streptokinase at extremely low temperatures. They found less plasminogen activation and fibrinogen degradation at 25 degrees C compared to 37 degrees C, but negligible differences at 10 degrees C, 0 degrees C and -8 degrees C. To our knowledge, there is no data studying the fibrinolytic activity of tissue plasminogen activator (tPA) at temperature ranges between 25-37 degrees C which is the range of temperatures used clinically for therapeutic purposes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778063 TI - Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. PMID- 7778064 TI - Mechanisms of the platelet aggregation induced by activated neutrophils and inhibitory effect of specific PAF receptor antagonists. AB - The supernatant of polymorphonuclear neutrophils after their activation by opsonized zymosan induces the aggregation of washed platelets in human. It potentiates platelet aggregation induced by agonists in platelet rich plasma as well as in whole blood. This activation involves the phosphoinositide metabolism. Specific PAF receptor antagonists gingkolides (BN 50726, BN 52021, BN 54068, BN 54062, BN 50730, BN 50749, BN 50744) and benzodiazepine Web2086 antagonize this neutrophil-induced platelet aggregation. BN 50,730, BN 50,749 and Web 2086 can fully inhibit this aggregation at the final concentration of 10(-6) M. Preincubation of platelets with synthetic PAF also inhibits this activation through a desensitization of the receptor. These data suggest the major involvement in our model of PAF acether in the platelet-neutrophil interactions. PMID- 7778065 TI - Zinc (II) selectively enhances the inhibition of coagulation factor XIa by protease nexin-2/amyloid beta-protein precursor. AB - Protease nexin-2 (PN-2) is the secreted isoform of the Alzheimer's Amyloid beta Protein Precursor (A beta PP) that contains the Kunitz-type protease inhibitor (KPI) domain. PN-2/A beta PP is a potent inhibitor of coagulation factor XIa (FXIa) and is secreted in large quantities by activated platelets suggesting a normal function in regulating this protease at sites of vascular injury. In the present study, the effect of Zn2+ on the protease inhibitory properties of PN-2/A beta PP was quantitatively investigated. Zn2+ (1 microM to 1 mM) had no effect on the inhibition of trypsin or chymotrypsin by PN-2/A beta PP. In contrast, Zn2+ at concentrations > 1 microM increased the inhibition of FXIa by PN-2/A beta PP. Enhancement of FXIa inhibition was virtually saturated at approximately 100 microM Zn2+ resulting in a final Ki approximately 6.0 x 10(-11) M. Zn2+ had no effect on the inhibition of FXIa by a purified, recombinant KPI domain of PN-2/A beta PP indicating that the native protein is required for the potentiation of FXIa inhibition. Heparin and Zn2+ were found to further augment each other's ability to stimulate the inhibition of FXIa by PN-2/A beta PP. Together, these findings suggest that the interaction of Zn2+ with PN-2/A beta PP may be important for optimal inhibition of FXIa. PMID- 7778066 TI - Endothelin influences pHi of human platelets through protein kinase C mediated pathways. AB - Stimulation of human platelets with endothelin raises cytosolic pH (pHi). In order to determine whether this effect is mediated via protein kinase C and Na(+) H+ linked pathways, the effects of staurosporine and calphostin C (protein kinase C inhibitors) and 5-(N,N-hexamethylene) amiloride (Na(+)-H+ exchange blocker) on endothelin-induced pHi responses in human platelets were assessed. In addition, platelet endothelin receptor subtypes were determined pharmacologically using the selective ETA receptor antagonist BQ-123 and the ETB receptor agonist sarafotoxin S6c. pHi was measured spectrofluorometrically using the fluorescent probe BCECF AM in platelets obtained from 15 healthy subjects. Endothelin-1 at a fixed concentration of 10(-9) M significantly increased pHi from 7.11 +/- 0.01 ([H+]i = 77 +/- 0.9 nM) to 7.19 +/- 0.04 ([H+]i = 64 +/- 0.9 nM) (p < 0.01). The pHi stimulating effect of endothelin-1 was inhibited by 10(-7) M staurosporine, calphostin C and 5-(N,N-hexamethylene) amiloride. BQ-123 (10(-7) M) abolished the pHi responses to endothelin-1, whereas sarafotoxin S6c had no effect on platelet pHi. These data suggest that in vitro effects of endothelin-1 on platelet pHi are receptor-mediated via a pathway involving protein kinase C. Platelet endothelin receptors appear to be of the ETA subtype. PMID- 7778068 TI - Bioavailability and pharmacokinetics of a new low molecular weight heparin (RO 11)--a three way cross-over study in healthy volunteers. AB - This study reports on the bioavailability and pharmaco kinetics of a new low molecular weight heparin (RO-11), with a mean molecular weight of 3,600-3,800 daltons. It was administered to 12 healthy individuals in an open, cross-over study. Each subject was randomly assigned to three experimental treatments: a) 30 mg by subcutaneous route, b) 60 mg subcutaneously and c) 60 mg intravenously, leaving a wash-out period of one week between treatments. The pharmacokinetic profile was calculated by means of the anti-FXa effect, measured on serial samples taken before and during the 24 h period after each treatment. The effects of the drug on global coagulation tests, Antithrombin-III levels, tissue-factor pathway inhibitor activity and anti-FIIa activity were also assessed. After the intravenous injection, a maximal anti-FXa effect of 1.30 +/- 0.18 IU/ml was measured at 0.05 h and was not measurable after 12 h. After the subcutaneous injection of 30 and 60 mg, the maximal anti-FXa effect (0.34 +/- 0.08 IU/ml and 0.54 +/- 0.06 IU/ml) was reached after 2-4 h, and was not measurable after 12-18 h. The magnitude of this effect was dose-dependent and the absorption and elimination processes followed a first-order pattern for every dose and route. RO 11 showed a biological half-life of about 5 h and a high subcutaneous bioavailability (96%). PMID- 7778067 TI - Activation of factors XII and VII induced in citrated plasma in the presence of contact surface. AB - Activated factor XII (XIIa), activated factor VII (VIIa) and factor VII coagulant activity (VIIc) were determined in non-treated and in treated (cold-incubated) citrated plasmas from women in late pregnancy and from norma volunteers. All three activities were higher in the non-treated plasmas from women in late pregnancy than from normal subjects. The incubation of citrated plasmas from women in late pregnancy, on ice for 24 hours, resulted in a many-fold increase of factor XIIa activity, factor VIIa levels and VIIc. The dilution of these plasmas resulted in a sharp decrease of all three activities in the post-incubation mixture, so that in the plasmas diluted 2:1 with buffer all three activities were similar to those in fresh plasmas. Similar incubations of diluted plasmas (1:1) from normal volunteers resulted in no increase of factor XIIa activity, factor VIIa levels and VIIc. However, the presence in the incubation mixture of micellar stearate resulted in a stearate concentration-dependent increase of all three activities in treated plasmas. Levels of factor XIIa activity and factor VIIa in the treated plasmas from both groups of subjects were highly correlated (r = 0.987; p < 0.001). There was also a highly significant correlation between VIIc and factor VIIa levels (0.989; p < 0.001). These results demonstrate that the in vitro increase in factor VIIa levels is due to the activation of the contact system of coagulation and is dependent on the potency of the contact surface. Moreover, VIIc over a wide range of values, observed in the present experiments, can provide an accurate measure of factor VIIa concentration. PMID- 7778069 TI - Thrombin treatment of endothelial cells stimulates adhesion of oncogene transformed but not parent rat liver epithelial cells. PMID- 7778070 TI - [Vaccine against Haemophilus influenzae type b. A new great achievement in the research on vaccines]. PMID- 7778071 TI - [Treatment of acute head injuries in Norway]. PMID- 7778072 TI - [Minor head injuries. May early CT-scanning replace in-hospital observation?]. AB - A one-year prospective study was undertaken to judge whether in-hospital observation after minor head injury could be partly replaced by early computerized tomography (CT), and if such a practice would save hospital resources. All 146 patients had a Glasgow Coma Score (GCS) > or = 14 and no neurological deficits. 128 had suffered loss of consciousness. CT of 97 (67%) patients revealed intracranial lesions in eight (contusions six, oedema one and epidural haematoma in one). Mean duration of hospitalization was 9.4 days in patients with intracranial lesions and 1.6 days in patients without such lesions. We observed no complications to the head injury in patients with normal CT. There is no need for hospitalization after minor head injury in patients with GCS > or = 14 with no neurological deficits and normal CT. We advocated wide use of early CT in cases of minor head injury, to allow early detection of intracranial haematomas, diagnoses of brain contusions and avoidance of unnecessary hospitalization. PMID- 7778073 TI - [Vaccine against Haemophilus influenzae type b--antibody response and adverse effects]. AB - In 1992 it was decided to implement vaccination against Haemophilus influenzae type b (Hib) in the Norwegian vaccination programme. The chosen vaccine consists of Hib-polysaccharide conjugated to tetanus toxoid. To suit the Norwegian vaccination schedule, Hib-vaccine was given together with vaccine against diphtheria, tetanus and pertussis (DTP) at three, five and ten months of age. Since all earlier studies with the Hib-vaccine have used other time schedules, a pilot study was conducted to test antibody response and side effects when using the Norwegian schedule. 44 infants were vaccinated with Hib-vaccine and DTP at three, five and ten months of age. Blood samples showed that 95% had protective antibody titer against Hib after two doses, 100% after three. The response to the other antigens was adequate. There were only minor side effects. After introduction of the Hib-vaccine the incidence of invasive Hib-infection in children below three years of age has decreased considerably. PMID- 7778074 TI - [Relation between erythrocyte sedimentation and C-reactive protein in serum of adults with lower respiratory tract infections. Significance of microbiological agents]. AB - Correlation between erythrocyte sedimentation rate and C-reactive protein was determined in 239 adult patients in general practice who were suspected of having an infection of the lower respiratory tract. A correlation coefficient of 0.62 (95% CI 0.54-0.69) was found, but there was no association between the results of the two tests when the illness had lasted less than four days. With such a short duration of illness a test for C-reactive protein is to be preferred before erythrocyte sedimentation rate when evaluating lower respiratory tract infections. PMID- 7778075 TI - [The value of C-reactive protein testing in suspected lower respiratory tract infections. A study from general practice on the effect of a rapid test on antibiotic research and course of the disease in adults]. AB - We wanted to assess whether routine use of a rapid test for C-reactive protein (CRP) could reduce prescription of antibiotics for adults with possible lower respiratory tract infection. 239 patients were randomized into a CRP group, tested with the rapid test (n = 108) and a control group (n = 121). Before knowing to which group the patient belonged the doctors made a preliminary decision about antibacterial treatment. The C-reactive protein value was then released if the patient belonged to the CRP group, and the therapy could be adjusted in light of the result. Antibacterial courses prescribed during the consultations and in the following three weeks were registered. The clinical course was evaluated by interview after one week and again after three weeks. Antibiotics were prescribed for altogether 56% of the patients in the CRP group and 60% in the control group. The difference was not statistically significant. Prescription of antibiotics was strongly associated with the finding of crackles and wheezes, but not with cough, dyspnoea or chest pain. Slow recovery was associated with high age, absence of fever and a normal value of C-reactive protein. No significant benefit of the CRP test was demonstrated. We discuss whether the doctors made full practical use of the information provided by the test. Bronchial obstruction should probably be considered to be the problem more often in coughing patients with a normal CRP value. PMID- 7778076 TI - [The effect of an antidepressive agent on premature ejaculation]. AB - Premature ejaculation is a common male sexual dysfunction. Many kinds of medication have been used without great success. The start-stop technique is usually preferred. However, some patients and couples do not want to learn this kind of sexual therapy. One common adverse effect of the new selective serotonin re-uptake inhibitors is delayed ejaculation. This article discusses a patient with a premature ejaculation problem combined with minor depression and anxiety, who was successfully treated with paroxetine. PMID- 7778077 TI - [How to monitor the development of a population of specialists? A method for prognostic estimation of needs in anesthesiology]. AB - The Norwegian Medical Association has been delegated responsibility for suggesting guidelines to monitor the quality and capacity of postgraduate specialist training. In every specialty, a committee for specialist training has to monitor the availability of specialists in their field on behalf of the Association. The authors describe a systematic approach to monitoring, in which available information was carefully matched with selected survey data, to enable prognostications. The method was then applied to anaesthesia, and revealed a need for higher production of specialists in this field. More than 10% of the 309 consultant anaesthetist positions were vacant, owing to lack of applicants, and another 36 consultants are needed to ascertain a minimum of three specialists in every hospital providing emergency services. 15% of the certified specialists did not work as anaesthesiologists. It was estimated that ten persons would leave annually, either to do research or take up another specialty, and that 15 would retire. Based on the findings, it is suggested that the present specialist production of about 20 per year should be increased to secure the nation's future need of anaesthesiologists. PMID- 7778078 TI - [Surgical treatment of acute head injuries, especially epidural hematomas. Current and future practice in Norway]. AB - A survey among the 13 general county hospitals and the five regional neurosurgical units in Norway showed that 263 patients were operated on for acute head injuries in 1993. More than 80% of these operations took place in a neurosurgical unit, and most county hospitals had only 1-2 such surgical procedures each year. Most county hospitals also limited their surgical activities to extradural conditions. Data from 68 patients operated on for epidural haematomas in our neurosurgical department were therefore analysed. The outcome of these operations was good in 83.8%, and only 5.9% showed a poor result. One patient died. It is concluded that these good results probably reflect the standard of handling, diagnostic work and transport of the patient prior to surgery, rather than the surgery itself. It seems unreasonable to continue the infrequent practice of treating these conditions surgically in local hospitals. PMID- 7778079 TI - [Diagnosis and treatment of headache]. AB - In the recent last decades, important advances have been made in the understanding of the mechanisms behind headache. This has resulted in more efficient treatment. New forms of headache have been described where a specific treatment can be used. Therefore, in order to give rational therapy to headache patients, the physician must be able to distinguish between the most important primary headaches. He should also be aware of the warning signals that should prompt further investigations or admission to hospital in search of underlying causes. The article describes the most important primary headaches and the current treatment, and discusses the problem of unclassifiable and untreatable headaches. PMID- 7778080 TI - [C-reactive protein and biological defense]. AB - This article reviews recent findings suggesting a specific tumouricidal effect of C-reactive protein (CRP). A peptidic fragment of CRP, called RS 83277, has shown a significant anti-tumour effect in laboratory animals. The mechanism is not fully understood, but is possibly mediated via the macrophages. Both macrophages and monocytes show increased tumoricidal activity after stimulation with RS 83277. The article also reviews the regulation of CRP synthesis and secretion, as well as the structure, binding capacities, and important biological properties of CRP. PMID- 7778082 TI - [Steady homosexual relationship and HIV infection]. AB - In order to study the relative impact of a steady homosexual relationship on the presence of HIV antibodies, a cross-sectional study was undertaken of 719 homosexual men in Oslo during the period of 1983-1987. 74/719 (10%) were HIV positive. 37/74 (50%) of the HIV positives and 185/645 (29%) of the HIV negatives were having a steady homosexual relationship that had lasted six months or more (chi-square test, p < 0.05). In a multivariate logistic regression analysis the adjusted odds ratio of being HIV positive was 2.3 (1.3-4.3, 95% confidence interval (CI)) for homosexual relationship lasting 1/2-4 years and 3.1 (1.5-6.6, 95% CI) for homosexual relationship lasting 5 years or more as compared with not being in a homosexual relationship. The number of male partners and frequent anal intercourse were also significantly associated with presence of HIV antibodies. The results suggest that situational variables associated with a steady partnership may be barriers to HIV-preventive measures. PMID- 7778081 TI - [The migraine remedy sumatriptan (Imigran) and coronary heart disease]. AB - The new drug, sumatriptan, used to treat migraine, causes substernal tightness and severe angina-like pain in 3-21% of patients. Several reports have described sumatriptan-induced death, ventricular fibrillation, myocardial infarction, ischaemia and coronary vasospasm. We describe the case of a woman aged 40 years who suffered from bronchial asthma but was without known coronary heart disease. She experienced chest pain after intake of 100 mg sumatriptan orally. ECG was normal and there was no increase in coronary enzymes. Sumatriptan has a weak coronary constrictor effect. Endothelial dysfunction, with reduced release of vasodilating nitric oxide, may potentiate vasoconstriction induced by sumatriptan in the presence of thromboxane A2. PMID- 7778083 TI - [Current medical education in Sweden]. PMID- 7778084 TI - [From the richness in knowledge to economic poverty--quo vadis, health and social occupations?]. PMID- 7778085 TI - [Fat-soluble vitamins in clinical practice]. PMID- 7778086 TI - [The Norwegian Society for Stroke]. PMID- 7778088 TI - [The world of concepts in social medicine]. PMID- 7778087 TI - [With Rudolf Ludwig Virchow as a guide into the new social medicine]. PMID- 7778089 TI - [Medical emergency service]. PMID- 7778090 TI - [An agreement on insurance in medical practice]. PMID- 7778091 TI - Building a testis. AB - Specific cellular, subcellular and acellular components of the rat testis including the capsule, the peritubular tissue (tunica propria) and the lymphatic endothelium were analyzed using morphometric techniques at cellular and subcellular levels to yield volume and surface area data. These data were integrated with previously published data for other cellular components of the rat testis to provide information about the volumetric composition for virtually every component of this organ. For major cell types (Leydig, Sertoli, myoid cells and germ cells) the data are expressed to the subcellular level in terms of volume and, in some instances, surface area. Graphic portrayals of testis constituents are used for rapid visual understanding of testis structure. The data presented herein are useful in conjunction with biochemical data to describe physiological properties of cells and cell components and also for understanding how structure differs under experimental and in pathological situations. PMID- 7778092 TI - Ultrastructural changes of female Syrian hamster cystic duct epithelium as a result of sex steroid treatment. AB - In view of the lack of sufficient data regarding the morphology of the cystic duct and the extensive focus on the gallbladder, a preliminary examination of the cystic duct response to female sex steroid treatment was conducted to follow up a detailed ultrastructural study of the gallbladder epithelial response to a similar treatment. As observed in the gallbladder epithelium, the cystic duct epithelial cells of nulliparous Syrian hamsters demonstrate morphologic changes in response to female sex steroid treatment. Control (C) cystic duct epithelial cells are covered by short microvilli and each cell appears to exhibit a single vestigial cilium. Estrogen (E)- and estrogen + medroxyprogesterone (E + MP) treatments induce differential duct cell morphologic changes. These changes are the result of steroid treatments in the significant decreasing sequence E > E + MP > C for nuclear volume, indentations and perinuclear lysosomal/lipofuscin bodies. Moreover E + MP-treatment results in larger cytoplasmic volume and more sloughing of apical cell excrescences than following E treatment. It is suggested that, similar to that in the gallbladder, the action of progestin is paramount in favoring cytoplasmic morphological changes in the cystic duct which, along with the alteration of mucus, cell sloughing, decreased bile acids and motility could also participate in the gallstone nucleation process as they are brought into the gallbladder with the incoming bile flow. PMID- 7778093 TI - Cystatin S in secretory granules fractions isolated from submandibular gland of infected rats by Trypanosoma cruzi. AB - We have measured the relative concentrations of cysteine proteinase in the granular fractions of submandibular glands of control and Trypanosoma cruzi infected rats by using a sensitive solid phase ELISA. Gland samples were homogenized in 0.34 M sucrose and 0.5 mM EDTA in 10 mM HEPES buffer at a pH of 7.4. The extract was centrifuged and filtered through Millipore filters to prepare a purer granular fraction. Immunochemical studies using antibody against cystatin S and electrophoretic analysis showed higher cystatin S levels in infected rats than in control. The role of this inhibitor during acute phase of Chagas disease is discussed. PMID- 7778094 TI - Adaptive cellular response to osmotic stress in pig articular chondrocytes. AB - The authors studied the effects of a wide range of medium osmolarities (from 0.28 osM (physiological osmolarity of plasma and synovial fluid) to 0.58 osM) by altering Na+ concentration in high density cultures of pig articular chondrocytes in order to analyze the behaviour of some functional and structural parameters during cell adaptation to these imposed changes in the ionic environment. Biochemical and morphological results indicated that, even if isolated from the tissue matrix and cultured in vitro, chondrocytes maintained active osmoregulation systems which are present in living conditions. They showed a similar biochemical and morphological behavior when cultured at 0.28 osM and 0.38 osM but they were able, with regard to protein synthesis, aminoacid transport and proliferation rates, to respond quickly and to adapt to 0.48 osM medium as well. On the contrary, the treatment at the highest osmolarity (0.58 osM) early altered these biochemical parameters and was detrimental or even gave rise to lethal damage during long-term treatment. Furthermore, while chondrocytes cultured in 0.28-0.38 osM medium maintained phenotypic characteristics in culture, the higher osmolarities (0.48-0.58 osM) caused morphological changes in cell populations resulting in loss of phenotypic cell stability as demonstrated by their taking on a fibroblast-like shape as well as a lack of ability to assembly matrix proteoglycans. PMID- 7778095 TI - Estrous cycle-related alterations in the expression of glycoconjugates and lectins in the mouse endometrium shown histochemically. AB - Alterations of the hormonal status may influence diverse cell features relevant to intra- and intercellular communication. We studied histochemically the expression of glycans and endogenous sugar-binding proteins (endolectins) in the mouse endometrium during the estrous cycle. The avidin-biotin-peroxidase complex (ABC) technique was used on paraffin sections with a panel of biotinylated lectins and neoglycoproteins. Stage-specific changes were observed with Galanthus nivalis agglutinin (GNA), Ulex europaeus-I agglutinin (UEA-1), Sambucus nigra agglutinin (SNA), Ricinus communis agglutinin (RCA-I) and Glycine max agglutinin (SBA) in both the luminal and the glandular epithelium, but to a lesser extent in the latter. The stromal constituents also exhibited modifications in lectin binding profiles in cyclic mice. In addition to the analysis of cell glycans endogenous carbohydrate-binding sites were studied using synthetic probes, biotinylated neoglycoproteins. These tools made it possible to conclude that hormonal status can affect the expression of endolectins. We have attempted to correlate the glycohistochemical findings with recently published data obtained biochemically. The results indicate that phase-specific alterations in lectin binding glycoproteins and endolectins occur in the endometrium of mice associated with their short reproductive cycle. PMID- 7778096 TI - Correcting cell density measurements for tissue hydration changes in scanning electron microscopy--application to the rabbit corneal endothelium. AB - Chemical fixation with glutaraldehyde (followed by osmium tetroxide treatment, methanol dehydration and critical point drying) of biological tissue can result in a reduction in tissue size. As a result, cell density estimates can be much higher than in the original tissue. For rabbit corneal endothelium (cell density of 3300 cells/mm2); preparation of fresh tissue (73% hydrated) results in a net 2 fold increase in apparent endothelial cell density unless the dimensions of the tissue before and after processing for scanning electron microscopy (SEM) are taken into consideration. The increase in endothelial cell density (ECD) is the same regardless of whether the fresh tissue is subjected to primary fixation for 1-14 days or if the fixed (and osmium tetroxide treated) tissue is stored in methanol for up to 80 weeks. However, if the tissue hydration is acutely altered during ex vivo perfusion techniques, the cell density, as assessed by SEM, is found to increase proportionately to the tissue hydration (as measured by corneal thickness); the increase was 600 cells/mm2 for each 100 microns increase in corneal thickness. The latter phenomenon does not appear to be the result of a differential reduction of tissue size associated with either primary fixation or secondary processing. For some tissues, therefore, a change in the tissue hydration level prior to fixation, may produce secondary effects in measures of cell densities. PMID- 7778097 TI - Response of guanylate cyclase to atrial natriuretic factor in epithelial cells of the frog choroid plexus. AB - This study shows that the choroid plexus of Rana esculenta contains a guanylate cyclase particulate (GCp), similar to that identified in Mammalia, that is quite sensitive to the atrial natriuretic factor (ANF). The cytochemical tests for GCp show that ANF increases the enzymatic reaction products. Deposits are observed on the apical portion, at the basal level and along the lateral edges of the epithelial cells, with the exclusion of some intercalary epithelial cells with reaction-lacking microvilli. In particular, ANF seems to intensely stimulate the GCp activity along the lateral membranes of the epithelial cells delimiting enlarged intercellular spaces, which are probably dilated for the transport of water and solutes. These data confirm the osmoregulatory role of the hormone and its control of cephalorachidian liquid composition. PMID- 7778098 TI - Proceedings of the Conference on Low-Level Exposure to Chemicals and Neurobiologic Sensitivity. Baltimore, Maryland, 6-7 April 1994. PMID- 7778099 TI - White paper: Chemical sensitivity: history and phenomenology. AB - Nearly everyone has heard something about chemical sensitivity, either from personal experience with someone who has the condition or from the media. The television series Northern Exposure recently featured a chemically sensitive attorney who lived in a geodesic dome in Alaska, and L.A. Law depicted the struggles of a Persian Gulf veteran with chemical sensitivities who lost his case against the Veterans Administration, but may appeal later in the season. Television news programs and the printed media have showcased patients living spartan existences in remote areas or in aluminum foil-lined rooms. Our views of the illness no doubt are colored by our own personal experiences of it. While some discount or make jokes about chemical sensitivity or these patients, physicians who have seen a number of them are discovering that many appear to be credible individuals with prior good work records who say they became ill following an identifiable exposure to chemicals. PMID- 7778100 TI - White paper: Neuropsychiatric aspects of sensitivity to low-level chemicals: a neural sensitization model. AB - The present paper summarizes the proposed time-dependent sensitization (TDS) and partial limbic kindling model for illness from low-level chemicals; reviews and critiques prior studies on CNS aspects of multiple chemical sensitivity (MCS); and outlines possible experimental approaches to future studies. TDS is the progressive and persistent amplification of behavioral, neurochemical, endocrine, and/or immunological responses to repeated intermittent stimuli over time. Partial limbic kindling is a progressive and persistent lowering of the threshold for eliciting electrical afterdischarges, but not motor seizures, in certain brain structures such as amygdala and hippocampus; behavioral consequences include increased avoidant behaviors. The focus of the paper is the controversial claim of altered sense of smell and illness from low levels of environmental chemicals (i.e., "cacosmia"), levels that should not have any biologically harmful effects by the rules of classical neurotoxicology. A major perspective of this paper is that the phenomenology of MCS is similar to that of time-dependent sensitization (reverse tolerance) and tolerance as studied in the substance abuse literature. The TDS model for MCS proposes that neurobiological amplification underlies the symptoms and phenomenology of these patients, including their behavioral features of heightened affective and somatic distress. It is hypothesized that MCS patients, who are mostly women, may be individuals who sensitize to substances rapidly and to the extreme, to the point of aversive symptomatology with less complete capacity for development of tolerance. Possible parallels between MCS and TDS include: (a) initiation by single or multiple intermittent stimuli; (b) lasting changes in subsequent reactivity to low levels of chemically unrelated substances; (c) cross-sensitization between the stressors and pharmacological agents; (d) greater vulnerability of individuals who are female, who have certain genetic characteristics, and/or who may be hyperreactive to novelty (cf. trait shyness); (e) lack of obvious differences between sensitized and unsensitized individuals at baseline without eliciting exposures; (f) bidirectionality (bipolarity) of sensitized responses; (g) both context dependent (conditioned) and context-independent (unconditioned) amplification of responses. To minimize variability between studies, research in this area needs (a) consensus on a working case definition of MCS or at least of cacosmia as a specific symptom in a subset of well-defined medical and psychiatric disorders; and (b) proper design of chemical challenge studies in MCS, controlling for individual differences in sensitizability and for the properties of sensitization (e.g., repeated intermittent exposure tests) and tolerance (e.g., removal from customary ambient air exposures prior to testing). PMID- 7778101 TI - Patient statement: chemically sensitive. AB - There are three areas of my experience with chemical sensitivity that may interest you. The first is the onset of this condition and what happened to me over time as I became chemically sensitive in my work place. The second is my experience with the "medical community." The third is the effect chemical sensitivity has had on my career. PMID- 7778103 TI - Time-dependent sensitization in animals: a possible model of multiple chemical sensitivity in humans. AB - It often happens in science that clues to the nature of a problem under study come from a completely different, seemingly unrelated, line of investigation. This may be the case with MCS and Time-Dependent Sensitization (TDS), a phenomenon we discovered in rats in the late 1970s and later named. TDS refers to the ability of mild stressors--whether pharmacological or environmental--to induce physiological and behavioral effects which then progress, i.e., get stronger, entirely as a function of the passage of time since stressor presentation. This strengthening is revealed when the organism is later exposed to either the original or another stressor. The characteristics of TDS bear a remarkable resemblance to the features of MCS and that similarity is the subject of this manuscript. PMID- 7778102 TI - Patient statement: chemical sensitivity--one victim's perspective. AB - Not a day goes by that I don't miss my old life and the old me. To illustrate how my life has changed, I have two brief stories. In 1982, I developed a lending procedure in conjunction with Banker's Life Insurance Company that enabled commercial real estate developers to secure permanent financing for property that had not yet been developed--in essence using a permanent loan in place of a construction loan. It fixed the interest rate, at a time when new construction rates were bankrupting many projects and it allowed the developer to invest the excess funds to offset interest expenses. I received national recognition for this loan. In 1989, the police found me wandering around in 15 inches of snow, in below zero weather with no shoes or coat. The officer took me to the hospital because I was obviously disoriented. I didn't even know my name or where I lived. These stories show the disparity between my life as a successful, independent business woman and my life as someone who is chemically disabled. PMID- 7778104 TI - Neuroanatomy and neurochemical mechanisms of time-dependent sensitization. AB - Time-dependent sensitization (TDS) is a phenomenon described in rodents as an enhancement in the behavioral and neurochemical responses to intermittent exposure to psychostimulant drugs. Time-dependent sensitization also occurs after repeated encounters with environmental stress. Several features of TDS parallel those of multiple chemical sensitivity (MCS) in humans, and these similarities have led to the hypothesis that MCS may be explained in part by a similar sensitization process that occurs in rodents. In the studies presented here, we discuss some of the critical features of TDS following repeated exposure to cocaine and environmental stress, including the anatomical and neurochemical pathways utilized in expressing TDS. In addition, we discuss the possible neurochemical basis for individual differences in responsiveness to stimuli, including novelty and cocaine. The striking similarities between TDS and MCS suggest it may be possible to develop an animal model of MCS, using TDS in rodents as its basis. PMID- 7778106 TI - Caveats in the use of the kindling model of affective disorders. PMID- 7778105 TI - Modelling anxiety disorders following chemical exposures. AB - The effects of kindling and inverse benzodiazepine receptor agonist beta carbolines on animal models of anxiety are briefly reviewed in relation to affective disorder associated with chemical exposure. Recent experimental results are described. In the present study, cats were given the inverse benzodiazepine receptor agonist, FG-7142, a powerful anxiogenic compound in humans and animals. Neural transmission in pathways involved in defensive behavior in the cat was monitored using evoked potential techniques. Change in these pathways was related to behavioral changes induced by the drug. It was found that a single dose of FG 7142 lastingly increased defensive response to rodents for at least 40 days after drug administration. Behavioral change was specific to defensive response, since approach-attack behavior remained unchanged, replicating previous studies. The benzodiazepine receptor antagonist, Flumazenil, reversed the increase in defensiveness in a drug-dependent manner, replicating previous findings. Increased defensiveness was paralleled by a delayed onset potentiation of neural transmission between the amygdala and the medial hypothalamus of the left hemisphere. Potentiation in the left hemisphere was transient, decaying between 6 and 12 days after the drug. There was a longer lasting potentiation (LTP) of activity evoked in the left and right amygdalo-periacqueductal gray pathways and in the right amygdalo-medial hypothalamic pathway. Potentiation in these pathways appeared at the time of behavioral change. Potentiation of the right amygdalo periacqueductal gray and right amygdalo-medial hypothalamic pathways persisted until the end of the experiment. In contrast, potentiation of the left amygdalo periacqueductal gray pathway faded by 40 days after the drug. Flumazenil decreased potentiation ony in the right amygdalo-periacqueductal gray pathway. These data strongly suggest that lasting affective change is mediated by lasting changes in particular efferents of the amygdala of the right hemisphere. Behavioral and physiological effects of FG-7142 were blocked by the N-methyl-D Aspartate (NMDA) receptor blocker, AP7. The data suggest that failure of neural inhibition induced by FG-7142 engages NMDA receptor processes to produce lasting potentiation of transmission in neural circuits that mediate defensive response with behavioral consequences. Since FG-7142 interferes with GABA mediated neural inhibition and is proconvulsant, its action might mimic the action of other environmental chemicals with similar properties, such as chlorinated hydrocarbon insecticides. The relationship of the present data to the literature on the neural and behavioral effects of insecticide exposure is discussed. The significance of these findings for multiple chemical sensitivity disorder is also briefly discussed. PMID- 7778107 TI - Neurobiological sensitization models of post-traumatic stress disorder: their possible relevance to multiple chemical sensitivity syndrome. AB - Neurological sensitization has been proposed as a model for post-traumatic stress disorder (PTSD) (Lipper et al., 1986; van der Kolk, 1987; Friedman, 1988; Post et al., 1988, 1994; Charney et al., 1993). Laboratory paradigms in which repeated exposure to a discrete stimulus is associated with progressive intensification of a neurophysiologic, behavioral, or pharmacologic response has many parallels with the sequence of events that precipitates PTSD. Investigators with other clinical interests have also been attracted to sensitization models. Specifically, Bell and associates (1992) have proposed that olfactory-limbic kindling is a very good model for understanding the etiology of multiple chemical sensitivity (MCS) syndrome. A number of articles in this volume have addressed the goodness-of-fit between this model and MCS. My major assignment is to review laboratory data and clinical observations pertinent to sensitization models of PTSD. I will show that although there are intriguing parallels between the two phenomena, one must have great respect for the complexity and polymorphism of both sensitization and PTSD before grasping for simplistic theoretical conclusions. Secondly, I will address the following question; if both PTSD and MCS can be understood as sensitization phenomena, are PTSD patients at greater risk to develop MCS and vice versa? This article is divided into four sections: a) a description of three distinct sensitization phenomena; b) a description of the symptoms of PTSD; c) a review of the applicability of sensitization models to the clinical phenomenology of PTSD; and d) a review of the hypothesis that PTSD patients might be more vulnerable to MCS. PMID- 7778108 TI - Drug sensitization, substance abuse, and chemical sensitivity. AB - Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. Much has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper. PMID- 7778110 TI - Psychological bases of symptom reporting: perceptual and emotional aspects of chemical sensitivity. AB - The reporting of physical symptoms is influenced to a large degree by psychological processes. Individuals are more likely to notice subtle sensations in environments lacking in stimulation than those demanding external attention. The beliefs or schemas that people hold dictate where and how they attend to their bodies as well. These normal perceptual processes help explain why people are often poor at accurately detecting internal physiological activity. Several individual differences are also related to the symptom reporting process. Females are more likely to base their symptom reports on external situational cues than are males. In addition, individuals with chronic anxiety--those high in Negative Affectivity (NA)--report more symptoms than those low in NA. Finally, individuals, who have had traumatic experiences, either in childhood or within 1 6 months prior to a major symptom reporting episode, tend to be high symptom reporters. Several recommendations are made to help researchers and clinicians distinguish between psychological or perceptual factors with presumed biological effects. One implication of this work is that MCS and allied syndromes should be viewed as both a mental and a physical health problem. PMID- 7778109 TI - Psychiatric symptoms in multiple chemical sensitivity. AB - Neuropsychiatric symptoms are among the most prominent manifestations of generalized chemical sensitivity. Patients, clinicians, and researchers are in agreement that symptoms such as depression, irritability, and mood instability are prominent among the distressing and disabling symptoms occurring in response to low-level chemical exposure. Beyond that point, however, agreement is difficult. The pathophysiology and clinical management of these symptoms remain quite controversial. This paper will review available data on the prevalence and form of psychiatric symptoms among those suffering from multiple chemical sensitivity. Various models explaining the relationship of psychiatric symptoms to chemical sensitivity will be discussed. Finally, the implications of these models for clinical management and future research will be reviewed. PMID- 7778111 TI - Neuropsychiatric status of patients with chronic fatigue syndrome: an overview. AB - Chronic fatigue syndrome (CFS) is an illness that results in debilitating fatigue as well as rheumatological, infectious, and neuropsychiatric symptoms. The present paper is a brief overview of the neuropsychological and psychiatric research on CFS. Studies from our laboratory contrasting CFS with patients with multiple sclerosis, depression, and healthy controls are detailed. Our hypothesis of neuropsychological impairments in CFS is discussed. PMID- 7778112 TI - The utility of psychophysiological measures in assessing the correlates and consequences of organic solvent exposure. PMID- 7778113 TI - Neuropsychology and psychology of MCS. AB - Neurological symptoms are frequently reported by patients with multiple chemical sensitivities (MCS). Methods to compare the psychiatric, personality, and neuropsychological function of patients with MCS, chronic fatigue syndrome (CFS), and normal controls are described. Increased rates of Axis I psychiatric diagnoses are observed in the literature for MCS and CFS subjects relative to controls. Findings on the MMPI-2 and the Toronto Alexithymia Scale reveal profiles consistent with the tendency to report somatic rather than emotional symptoms in response to stress. However, many of the reported somatic symptoms also coincide with those found in neurologic disorders. The overall neuropsychological profile for MCS subjects does not reflect cognitive impairment. Relative to normal controls, the only difference in neuropsychological performance observed is reduced recognition of nontarget designs on a visual memory task. More fruitful areas for future psychological research will include measurement of the interaction between behavioral response styles and attentional processes in cognition, as well as observations under controlled challenge conditions. PMID- 7778116 TI - EEG and ERP studies of low-level odor exposure in normal subjects. AB - Evidence from four EEG/ERP experiments is presented. Findings of these experiments consistently demonstrate the ability of low-level and undetected odors to alter neurophysiology. Behavioral and cognitive effects are also described. These data may have applicability to theories of MCS since they illustrate the possibility that low-level or undetected odors affect central nervous system activity and may precipitate or cue MCS symptoms. PMID- 7778114 TI - NeuroSPECT findings in patients exposed to neurotoxic chemicals. AB - Exposures to neurotoxic chemicals such as pesticides, glues, solvents, etc. are known to induce neurologic and psychiatric symptomatology. We report on 41 patients--16 young patients (6 males, 10 females, age 34 +/- 8 yrs.) and 25 elderly patients (9 males, 16 females, age 55 +/- 7 yrs). Fifteen of them were exposed to pesticides, and 29 to solvents. They were studied with quantitative and qualitative analysis of regional cerebral blood flow (rCBF), performed with 30 mCi of Xe-133 by inhalation, followed by 30 mCi of Tc-HMPAO given intravenously. Imaging was performed with a brain dedicated system, distribution of rCBF was assessed with automatic ROI definition, and HMPAO was normalized to maximal pixel activity in the brain. Results of Xe rCBF are expressed as mean and S.D. in ml/min/100g, and HMPAO as mean and S.D. uptake per ROI, and compared with age-matched controls--10 young and 20 elderly individuals. table: see text] We conclude that patients exposed to chemicals present with diminished CBF, worse in the right hemisphere, with random presentation of areas of hypoperfusion, more prevalent in the dorsal frontal and parietal lobes. These findings are significantly different from observations in patients with chronic fatigue and depression, suggesting primary cortical effect, possibly due to a vasculitis process. PMID- 7778115 TI - Single photon emission computed tomography of the brain in patients with chemical sensitivities. AB - Chemical sensitivities display a recurrent pattern on scintigraphic examinations of the brain. The pattern can include mismatching between early and late imaging, multiple hot and cold foci distributed throughout the cortex without regard to lobar distribution (salt and pepper pattern), temporal asymmetries, and sometimes increased activity in the basal ganglia. This study used Desert Shield/Desert Storm veterans who present with abnormal neurological and psychological symptoms as a model to exhibit abnormalities by brain scintigraphy. These are typical of those seen in patients with documented exposure to neurotoxic compounds who develop a clinical syndrome that has been termed "chemical sensitivity." Exposure to cocaine, alcohol, and other substances of abuse can result in abnormal scintigrams of the brain using tracers such as [technetium 99m]hexamethylpropyleneoxime. This study used techniques combining regional cerebral blood flow data with delayed distributional data after the intracellular conversion of the tracer into a hydrophilic molecule. In addition to delayed image abnormalities, a mismatch occurs in the regional activity between the two image sets of the veterans. This degree of mismatch was not seen in control subjects who were screened for avoidance of neurotoxic agents. Patterns identified from examinations performed on patients with known exposure to petroleum distillates, pesticides and other materials linked with neurotoxicity were identified in some veterans of the Desert Shield/Desert Storm operation. A single case of repeated examinations on a veteran showed a reversion of these patterns toward normal after therapy. This reversion followed independent assessments of clinical improvement. PMID- 7778117 TI - Olfactory (chemosensory) event-related potentials. AB - Chemosensory event-related potentials (CSERPs) have found their way into a number of fields of research where they help to determine the function of both the trigeminal and the olfactory system. The investigation of chemosensory deficits in patients with Parkinson's or Alzheimer's disease is only one of the typical applications. It can be assumed that scientists involved in research on patients with multiple chemical sensitivities will also benefit from having access to objective data covering different aspects of the sense of smell. PMID- 7778118 TI - Low-level chemical sensitivity: a perspective from behavioral toxicology. AB - Low-level chemical sensitivity is hardly a new issue in environmental toxicology. It is, in fact, the focus of risk assessment. The risk assessment process is designed explicitly to estimate the health threats posed by low exposure levels, typically by extrapolating from high experimental or environmental levels. The conventional risk assessment structure, however, was designed primarily around cancer. It is only awkwardly applicable to neurobehavioral toxicants because of the multiplicity of endpoints that have to be considered in evaluating neurotoxicity. At the same time, neurotoxic risk assessment maintains certain advantages over cancer risk assessment because of diminished uncertainties over dose extrapolation. It does not have to depart as far from the range of observable data. The main problem with extending the risk assessment model to issues such as Multiple Chemical Sensitivity (MCS) and Sick Building Syndrome (SBS) is the absence of a specific chemical whose concentration can be measured and then manipulated. A prototypical agent, however, such as a volatile organic solvent, might be selected and studied. Beyond the choice of agent, however, is the question of which behavioral criteria are likely to yield the most useful information. Although neuropsychological test batteries provide one source of data, they typically are administered in a setting other than the one allegedly provoking the syndrome. A different approach invokes what might be called a miniature work situation. Here, a test subject is evaluated in a setting that emphasizes sustained performance testing in the presence of target chemicals. Experimental design is another factor to be considered. Two features are especially critical. The most sensitive design, at least for the current stage of knowledge, would probably emphasize consistency of response, and would choose as subjects individuals who claim to be afflicted with low-level sensitivity. Consistency in a single individual may be more informative than significance tests in a large sample. In addition, consistency as a criterion helps overcome the problem that, in any such sample, only a minor proportion of the subjects may truly exhibit such sensitivity. At a later stage, a broader range of subjects might be targeted. Research on behavioral disorders evoked by food additives illustrates the importance of such questions. It also demonstrates that the methods currently used to assess the potential toxicity of many substances, including food additives, typically ignore subtle, and often sensitive, neurobehavioral measures. PMID- 7778119 TI - Multiple chemical sensitivity: lessons from seasonal affective disorder. PMID- 7778120 TI - EEG responses to low-level chemicals in normals and cacosmics. AB - Recent studies from the University of Arizona indicate that normal subjects, both college students and the elderly, can register the presence of low-intensity odors in the electroencephalogram (EEG) in the absence of conscious awareness of the odors. The experimental paradigm involves subjects sniffing pairs of bottles, one containing an odorant (e.g. isoamyl acetate) dissolved in an odorless solvent (water or liquid silicone), the other containing just the solvent, while 19 channels of EEG are continuously recorded. For the low-intensity odor conditions, concentrations are adjusted downward (decreased) until subjects correctly identify the odor bottle at chance (50%). The order of odorants, concentrations, and hand holding the control bottle, are counterbalanced within and across subjects. Three previous experiments found that alpha activity (8-12 hz) decreased in midline and posterior regions when subjects sniffed the low intensity odors. The most recent study suggests that decreased theta activity (4 8 hz) may reflect sensory registration and decreased alpha activity may reflect perceptual registration. In a just completed experiment involving college students who were selected based on combinations of high and low scores on a scale measuring cacosmia (chemical odor intolerance) and high and low scores on a scale measuring depression, cacosmic subjects (independent of depression) showed greater decreases in low-frequency alpha (8-10 hz) and greater increases in low frequency beta (12-16 hz) to the solvent propylene glycol compared to an empty bottle. Topographic EEG mapping to low-intensity odorants may provide a useful tool for investigating possible increased sensitivity to specific chemicals in chemically sensitive individuals. PMID- 7778121 TI - Critique: SPECT studies of multiple chemical sensitivity. PMID- 7778122 TI - Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan. AB - A molecular investigation was conducted on the production of type II ribotoxin of the species Aspergillus and related fungi in Taiwan. Species that carried ribotoxin were confirmed by (1) cross-reactivity to anti-alpha-sarcin serum; (2) Southern dot hybridization; (3) PCR amplification of genomic DNA with specific primers; and (4) analysis of ribotoxic activity. Five new strains, A. clavatus, A. oryzae var. effusus, A. ostianus, A. tamarii, and Neosartorya fischeri var. spinosa, were identified to contain an alpha-sarcin-like ribotoxin. These positive strains exhibit ribotoxic activity by cleaving ribosomes and generating an alpha-fragment. PMID- 7778123 TI - Binding of muscarinic toxins MTx1 and MTx2 from the venom of the green mamba Dendroaspis angusticeps to cloned human muscarinic cholinoceptors. AB - Muscarinic toxins MTx1 and MTx2 are 7500 mol. wt polypeptides isolated from the venom of the green mamba snake Dendroaspis angusticeps. Previous competition binding studies indicate that the MTxs may be selective for the M1 subtype of muscarinic acetylcholine receptors. The present work was undertaken in order to clarify the muscarinic subtype specificity and functional effects of MTx1 and MTx2. Binding interactions were determined using 3H-N-methyl scopolamine (NMS) and cloned human muscarinic receptor subtypes m1, m2, m3 and m4. Some preliminary functional studies were performed on rabbit vas deferens preparations, which contain M1 cholinoceptors. MTx1 and MTx2 inhibited 3H-NMS binding to m1 and m3 receptors, with little effect on binding to m2 and m4 receptors. Affinity was higher for m1 receptors: Ki for MTx1 were 48 nM at m1 receptors and 72 nM at m3 receptors, and Ki for MTx2 were 364 nM at m1 and 1.2 microM at m3 receptors. At m1 receptors, about 90% of the binding of MTx1 and MTx2 appears to be irreversible. On rabbit vas deferens preparations, MTx1 and MTx2 at concentrations above 50 nM behaved in a similar way to the relatively selective M1-agonists McN-A-343 and CPCP (4-[N-(chlorophenyl)carbamoyloxy]-4-20-ynyl trimethylammoniu m iodide) by reducing responses to nerve stimulation. The results confirm that MTx1 and MTx2 bind to m1 receptors rather than to m2 or m4 receptors, but they also reveal a slightly weaker effect at m3 receptors. The interaction at m1 receptors appears to be essentially irreversible, implying that the toxins could be useful tools in studies of the functional role of m1 muscarinic receptors. PMID- 7778124 TI - A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri. AB - Waglerin-I, a lethal toxin isolated from the venom of Trimeresurus wagleri, consists of 22 amino acid residues with a proline-rich sequence. In the present study, we investigated the cause of death and the possible site of action of this toxin. In anesthetized mice, i.v. administration of waglerin-I at 0.5 microgram/g produced respiratory failure within 5 min. The blood pressure could be maintained by the application of artificial respiration immediately after respiratory arrest. Waglerin-I at 4 microM reversibly blocked the indirect twitch of the mouse phrenic nerve-hemidiaphragm preparation, but had no effect on the direct twitch. It is concluded that respiratory failure, resulting from neuromuscular block, is the primary cause of death due to waglerin-I in mice. In contrast to the results obtained in mice, in anesthetized rats no toxic effects on respiration and blood pressure were observed except for a transient hypotension up to 10 micrograms/g (i.v.). In accordance with the in vivo experiments, waglerin-I at concentrations up to 40 microM did not block the indirect twitch of the rat diaphragm. It thus appears that rats are resistant to the toxic effects of waglerin-I. PMID- 7778125 TI - Bibliography of toxinology. PMID- 7778126 TI - Isolation and characterization of a metalloproteinase with weak hemorrhagic activity from the venom of the snake Bothrops asper (terciopelo). AB - A metalloproteinase, named BaP1, was purified to homogeneity from the venom of Bothrops asper (Pacific region) of Costa Rica by ion-exchange chromatography on CM-Sephadex and gel filtration on Sephacryl S-200. The enzyme has a mol. wt of 24,000 and contains few Cys and high numbers of Asp, Leu, Ser and Glu. BaP1 hydrolyzes casein, hide powder azure and fibrinogen, having an optimal pH of 8.0. It rapidly digests the A alpha-chain of fibrinogen and, later on, the B beta chain, leaving the gamma-chain unaffected. Chelating agents (EDTA and 1,10 phenanthroline) inhibited proteolytic activity, whereas 2-mercaptoethanol and soybean trypsin inhibitor did not affect this activity. BaP1 has a weak hemorrhagic activity, with a minimum hemorrhagic dose of 20 micrograms; this activity was inhibited by EDTA and was abolished after incubation at 60 degrees C. In addition, BaP1 induces edema and a mild myotoxic effect, lacking coagulant, defibrinating and lethal effects. PMID- 7778127 TI - Pharmacological study of edema induced by venom of the snake Bothrops asper (terciopelo) in mice. AB - The effect of several drugs on the edema-forming activity of Bothrops asper venom was studied plethysmographically using the mouse foot pad assay. Bothrops asper venom induced a dose-dependent edema which developed rapidly and peaked 1 hr after envenomation. Incubation of venom with EDTA before injection resulted in a significant reduction of edema. In addition, pretreatment with prazosin, indomethacin, dexamethasone, yohimbine and mepacrine resulted in a significant reduction in edema-forming activity. However, no inhibitory effect was observed when mice were pretreated with verapamil, nordihydroguaiaretic acid, pyrilamine, cimetidine and propranolol. When drugs were administered after venom injection, only prazosin and indomethacin were effective in reducing edema. These results suggest that B. asper venom-induced edema in the mouse foot pad model is mediated, at least partially, by metalloproteinases, phospholipase A2, eicosanoid products and activation of alpha 1 and alpha 2 adrenergic receptors. PMID- 7778128 TI - Medium molecular weight factor X activating enzyme from Vipera berus berus venom. AB - Vipera berus berus venom contains several factor X activating enzymes. One of them (VBFXAE) was separated by gel-filtration on Sephadex G-100 superfine and on a bacitracin-agarose column. The enzyme is a single-chain glycoprotein with mol. wt 38,000. The enzyme has several molecular forms with pI 3.5-4.5. After neuraminidase treatment the enzyme has pI 4.5. VBFXAE contains 2 Ca per mole. The activator is inactive on synthetic substrates, on casein, prothrombin, and fibrinogen, and appears to act specifically on factor X. The activator also weakly hydrolyses the insulin B-chain at the positions Ala14-Leu15 and Tyr16 Leu17. The cleavage of the insulin B-chain is inhibited by EDTA, suggesting the metalloproteinase nature of the enzyme. PMID- 7778129 TI - The effect of cleavage by a Crotalus atrox alpha-proteinase fraction on the properties of C1-inhibitor. AB - The effect of cleavage of C1-inhibitor at Pro36 by a Crotalus atrox alpha proteinase fraction on the properties of this serpin was studied. This truncated C1-inhibitor (des 1-36) was fully active as an inhibitor of kallikrein, beta factor XIIa, and C1s, and modulated the functions of C1 in a normal manner. Also, the half-life of the truncated protein in the circulation of rabbits, both alone and in complex with C1, was not altered. These results show that shock-like symptoms caused by C. atrox envenomation are not attributable to a deficiency in C1-inhibitor caused by the action of the metalloproteinase in the alpha proteinase fraction. PMID- 7778130 TI - A major lethal factor of the venom of Burmese Russell's viper (Daboia russelli siamensis): isolation, N-terminal sequencing and biological activities of daboiatoxin. AB - A major lethal factor, daboiatoxin (DbTx), showing strong PLA2 activity (specific activity 91.7 nmoles/min/mg), was purified to homogeneity from the venom of Burmese Russell's viper (Daboia r. siamensis) by a combination of gel filtration on Sephadex G-75 and ion-exchange chromatography on CM-Sephadex C-25, followed by purification on high-performance gel filtration Shim-pack Diol-150 column. DbTx is a single-chain PLA2 toxin with approximate mol. wt 15,000 as determined by HPLC gel filtration and SDS-PAGE. It constitutes 12% of total venom protein and is the main lethal component of Burmese Russell's viper venom with an LD50 i.p. (0.05 mg/kg) 12-fold greater than that of the whole venom (LD50 i.p. 0.6 mg/kg). DbTx produces neurotoxic symptoms in mice and exhibits potent oedema-inducing activity (minimum oedema dose 0.05 microgram), indirect haemolytic activity and a strong myonecrotic activity, but no haemorrhagic activity. DbTx is cytotoxic to HeLa cells causing cytolysis of the cells 24 hr post-exposure to toxin (50 micrograms/ml). The first 20 N-terminal amino acid sequence (NFFQF AEMIV KMTGK EAVHS) shows a significant resemblance to those of the PLA2s from the venoms of Bulgarian viper (V. a. ammodytes) and Taiwan Russell's viper (V. r. formosensis). PMID- 7778131 TI - Therapeutic effects of antivenom supplemented by antithrombin III in rats experimentally envenomated with Russell's viper (Daboia russelli siamensis) venom. AB - The effects of equine antivenom and antithrombin III (AT-III) on the coagulopathy induced by Russell's viper venom (RVV, Daboia russelli siamensis) were investigated in the rat. After taking blood samples from the femoral vein for determination of simple blood clotting time and AT-III activity, all anaesthetized rats received an intramuscular injection of venom (2 micrograms/g). Treatment (antivenom or AT-III or both) was given intravenously through another femoral vein 30 min after venom injection. All untreated rats (n = 7) developed AT-III depletion (< 70%) [mean (S.D.)] 70 (36) min, and incoagulable blood 85 (53) min after venom injection. Supplementation with AT-III (either 0.25 U/g or 0.5 U/g) had no effect on the RVV induced coagulopathy (n = 20). Treatment with antivenom alone (10 micrograms/g) reduced the incidence of abnormal clotting significantly (8/15, 53%) (P = 0.03). When antivenom was given in combination with AT-III (0.5 U/g), abnormal clotting was prevented in all but one animal (1/15, 7%) (P = 0.007). AT-III activity declined progressively in all rats which developed non-clotting blood. These results suggest that coagulopathy in Russell's viper envenoming is associated with activation of coagulation and consumption of AT-III. Antivenom can prevent coagulopathy, but its neutralizing activity is augmented significantly by AT-III supplementation. PMID- 7778133 TI - Antivenom activity of opossum (Didelphis marsupialis) serum fraction. AB - We have found an opossum serum fraction of approximately 97,000 mol. wt to be highly proficient in inactivating the haemorrhagic and proteolytic fractions of Bothrops lanceolatus venom. This antivenom substance, isolated from opossum serum or a synthetic peptide based on the aforementioned protein, would probably be useful in the medical management of Bothrops accidents. PMID- 7778132 TI - Purification and amino acid sequence of the insecticidal neurotoxin Tx4(6-1) from the venom of the 'armed' spider Phoneutria nigriventer (Keys). AB - An insecticidal peptide referred to as Tx4(6-1) was purified from the venom of the spider Phoneutria nigriventer by a combination of gel filtration, reverse phase fast liquid chromatography on Pep-RPC, reverse-phase high performance liquid chromatography (HPLC) on Vydac C18 and ion-exchange HPLC on cationic columns. Tx4(6-1) is highly toxic to house flies. At levels of 0.5 ng/house fly it caused excitatory symptoms immediately after intrathoracical injection. However, in mice injections of 0.03 mg of the toxin intracerebroventricularly resulted in no apparent symptoms of intoxication. These results demonstrate that Tx4(6-1) of P. nigriventer has no toxicity for mice, and suggest that it is a specific anti-insect toxin. The mol. wt (5244.6) and purity of the toxin were determined by desorption mass spectroscopy. The complete amino acid sequence of this toxin was established by direct automated Edman degradation and manual 4 N,N'-dimethylaminoazobenzene-4'isothiocyanate/phenyl-isothiocyanate microsequence analyses of peptides obtained from digests with various proteases. The protein contains 48 amino acids including 10 Cys and 6 Lys. The N-terminal and C-terminal residues were Cys. The Tx4(6-1) sequence differs from that of previously characterized neurotoxins found in the same and other venom spiders, but exhibited sequence similarities in the location of the Cys residues. PMID- 7778134 TI - The antibody response in seabather's eruption. AB - Thirty-six of 44 patients with seabather's eruption had specific IgG antibodies against Linuche unguilata (thimble jelly) medusae antigen. ELISA detected antibodies in serum stored for 10 years. The extent of the cutaneous eruption or sting severity was correlated with antibody titer. Antibodies were detected in patients acquiring the eruption in Florida, the Bahamas and Aruba, reflecting the habitat of these jellyfish. This serological assay can be useful to confirm the clinical diagnosis. PMID- 7778135 TI - A small scale field trial with expanded polystyrene beads for mosquito control in septic tanks. AB - A field trial of the use of expanded polystyrene beads (EPSB) to control the breeding of mosquito larvae in household septic tanks was conducted in Sarawak. One week after treatment, the breeding of Culex quinquefasciatus and Aedes albopictus was reduced by 100% and 68.7% respectively. For both species combined, a 57.25% reduction in the adult emergence rate was achieved. No adult was caught in the emergence trap one month after treatment. A reduction in mosquito biting rates was reported by 87.3% of respondents. All households regarded the EPSB treatment as effective. This study has reduced the relatively high infestation rate of A. albopictus in the septic tanks to 16-20%. The EPSB treatment is feasible and practical. Post-treatment assessment using adult emergence traps and the implications for the vector control programme of the local authority are discussed. PMID- 7778137 TI - Socio-economic risk factors for malaria in a peri-urban area of The Gambia. AB - Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value. PMID- 7778136 TI - An epidemic of Plasmodium falciparum malaria in Balcad, Somalia, and its causation. AB - The causative factors of an epidemic of falciparum malaria were investigated in Balcad, Somalia, a town with previously low malaria transmission, where malaria incidence rose more than twenty-fold between 1986 and 1988. The emergence of chloroquine resistance, accelerated by high drug pressure, low herd immunity and favourable meteorological conditions were identified as major causes of the epidemic. Chloroquine resistance of grades RII and RIII was first observed in Balcad in 1987 and rapidly increased to 72% of the Plasmodium falciparum infections in 1988. In the absence of alternative treatment, resistance resulted in the accumulation of a massive infective reservoir and therefore increased malaria transmission, associated with intensive clinical symptomatology. The advent of chloroquine resistance was less violent in the area of Malable, where malaria is stable and communal immunity higher than in Balcad. PMID- 7778138 TI - Socio-economic determinants are not major risk factors for severe malaria in Gambian children. AB - Only a small proportion of subjects infected with Plasmodium falciparum develop severe disease. Why this should be is not fully understood. To investigate the possible importance of socio-economic variables on the severity of malaria in Gambian children we undertook a case-control study of 384 children with severe or mild malaria. Few differences were found between the 2 groups. Children with severe malaria had a longer duration of symptoms when recruited than mild cases but this difference was largely accounted for by the fact the most children with severe disease were recruited at a referral hospital, whilst mild cases were recruited at a primary health care facility nearer their home. There was no difference between groups in the time before mothers sought some form of health care. Mothers of children with severe disease were less ready to take their child to hospital than mothers of mild cases, suggesting that education on the importance of taking a child with features of malaria to a health centre as soon as possible might have some effect on the development of severe disease. However, overall, the results of this study suggested that socio-economic and behavioural factors are not the major determinants for severe malaria in African children. PMID- 7778140 TI - Visceral leishmaniasis and HIV-1 co-infection in southern France. AB - Between 1986 and 1993 visceral leishmaniasis (VL) was diagnosed in 50 adult patients with human immunodeficiency virus type 1 (HIV-1) infection (8 females, 42 males: 31 intravenous drug users, 11 homosexual or bisexual men, 6 heterosexual individuals, 2 blood recipients) from 5 hospital centres in southern France. Diagnosis of VL was by demonstration of Leishmania and isolation of promastigotes by culture in Novy-McNeal-Nicolle medium. Leishmania isolates were identified by their isoenzyme profile in 28 patients. All the patients were immunocompromised when VL was diagnosed. Their median CD4 cell count was 25 x 10(6) (0-200). However, only 21 patients (42%) fulfilled the 1987 CDC criteria for the acquired immune deficiency syndrome before VL developed. Fever (84%), splenomegaly (56%), hepatomegaly (34%), and pancytopenia (62%) were the most common presenting features. Clinical signs were lacking in 10% of patients. Anti leishmanial antibodies were detected by indirect immunofluorescence or enzyme linked immunosorbent assay in 26/47 cases (55%). Combining these techniques with Western blotting (WB) gave a positivity rate of 95%. Amastigotes were demonstrated in bone marrow aspirates in 47 cases (94%). Unusual sites for parasites were found in 17 patients (34%), mainly in the digestive tract but also skin and lung. Viscerotropic L. infantum zymodeme MON-1 was characterized in 86% of cases. Dermotropic zymodemes MON-24, MON-29, MON-33, and a previously undescribed zymodeme MON-183, were isolated from 4 patients. The response rate to pentavalent antimony was 50% and to amphotericin B 100%, but clinical relapses were noted in both groups. In endemic areas, VL should be considered as a possible opportunistic infection in HIV-infected patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778139 TI - Visceral leishmaniasis in a new ecological niche near a major metropolitan area of Brazil. AB - In 1991, a community cross-sectional study was conducted in a village situated near the beach and close to Salvador, the capital city of Bahia, in Brazil, to determine the prevalence of visceral leishmaniasis since 1989. A serological survey was made of human and canine reservoirs and an intradermal skin test for leishmaniasis was used to assess cellular immune responses. Nearly 30% of the 243 individuals in the study area had positive skin tests and 14% had positive serology, the latter being compatible with recent infection; 29 of 460 dogs examined were seropositive. A possible association was observed between human infection and the presence of dogs in or near residences, but not between human infection and malnutrition. This report describes the evolution of a new focus of visceral leishmaniasis, its expansion toward a metropolitan area, and current measures taken to control the epidemic. PMID- 7778141 TI - Epidemiology of subperiodic Wuchereria bancrofti infection in the Nicobar Islands, India. AB - Diurnally subperiodic filariasis due to Wuchereria bancrofti has been reported from tribal populations in the Nancowry group of islands in the Andaman and Nicobar Islands, India. This was confirmed in a survey carried out during the monsoon season in 1993. Microfilariae were detected in the peripheral blood throughout a 24 h period with a peak at 18:00. The microfilaria (mf) rate ranged from 1.2% to 18.7%, with a low disease rate (mean = 1.9%). Incidence of mf was low in children less than 10 years old (3.5%), but increased with increasing age. Culex (Culex) quinquefasciatus was present at a very low density. Aedes (Finlaya) niveus and Aedes (Stegomyia) malayensis were the only species commonly biting man. The former was incriminated as a vector, and found naturally infected with W. bancrofti (infection and infectivity rates 1.1% and 0.9% respectively). After experimental feeding on donors, W. bancrofti developed to L3 stage larvae in A. niveus but failed to develop in A. malayensis and A. aegypti. PMID- 7778142 TI - Effect of iron and pH on the survival of Vibrio cholerae in water. AB - Many physicochemical factors affect the survival of Vibrio cholerae in the aquatic environment. An attempt was made to study the combined effect of pH and iron on the survival of V. cholerae in water in a laboratory environment. None of the 6 strains of V. cholerae used survived at pH 5.0; survival of all strains increased with increasing pH. The effect of ferric oxide on survival was significant for V. cholerae O1 only, not for non O1 strains. The longest survival of V. cholerae non O1 was 82 d, of El Tor V. cholerae 68 d, and of classical V. cholerae 56 d. PMID- 7778143 TI - The epidemiology of snake bite in Central Province and National Capital District, Papua New Guinea. AB - Snake bite is an important medical problem in some areas of Papua New Guinea and appears to be most common in the Central Province and National Capital District. The overall incidence for Central Province is 215.5 per 100,000 population, but Kairuku subprovince has an incidence of 526 per 100,000, which is amongst the highest in the world. The clinical pattern of envenoming also varies within the Province, suggesting that different species of snake may be responsible for bites in different areas. Most envenomed patients are bitten during daylight on the lower limb and are rarely able to describe the snake. The mortality rate in Central Province is 7.9 per 100,000; most patients die from ventilatory failure due to severe neurotoxicity. Mortality might be reduced by increased use of compression bandaging as a first aid measure, earlier treatment with antivenom and earlier referral to hospital. PMID- 7778144 TI - Visceral leishmaniasis in Bangladesh: the value of DAT as a diagnostic tool. AB - The direct agglutination test (DAT) was performed on 480 serum samples from suspected cases of visceral leishmaniasis (VL) in different parts of Bangladesh. Significant titres (> or = 1:3200) were found in 257 sera (53.5%). All patients with positive bone-marrow aspirates also had significant DAT titres. The male:female seroprevalence ratio was 2:1 and the age-group 0-20 years was the most affected. The DAT proved a simple, economical and reliable diagnostic test for VL. PMID- 7778145 TI - Polymerase chain reaction-solution hybridization enzyme-linked immunoassay (PCR SHELA) for the differential diagnosis of pathogenic and non-pathogenic Entamoeba histolytica. PMID- 7778146 TI - Detection of dengue virus from mosquito cell cultures inoculated with human serum in the presence of actinomycin D. AB - We report the use of cultures of mosquito cells (TRA-284) to detect dengue virus in serum from cases of dengue fever in the state of Puebla, Mexico. Using the conventional procedure 56 of 171 samples (32.7%) were positive. The negative sera (67.3%) were passaged 'blind' in mosquito cell cultures but no virus was detected. However, when these sera were incubated in the presence of actinomycin D (an inhibitor of deoxyribonucleic acid transcription) 20 of the 115 samples (17.4%) became positive. This procedure increased the virus detection rate from 32.7% to 44.4%. Serotypes 1 and 4 were identified for the first time in the state of Puebla, where the transmission of dengue virus is increasing. The addition of actinomycin D to mosquito cell cultures may improve the detection of dengue virus and could be a useful tool for virological surveillance in endemic countries. PMID- 7778147 TI - Massive splenomegaly responsive to proguanil and with features of hairy cell leukaemia. AB - A recent Ethiopian immigrant to Israel presented with pneumococcal sepsis, massive splenomegaly and lymph-adenopathy. Investigations revealed many features of both hairy cell leukaemia (HCL) and hyperreactive malarious splenomegaly (HMS). Proguanil therapy for HMS was followed by rapid, marked decrease in spleen size, disappearance of the tartrate-resistant acid phosphatase-positive cells characteristic of HCL, and increasing eosinophilia, but unchanged lymphadenopathy. PMID- 7778148 TI - Fever in uncomplicated Plasmodium falciparum infection: effects of quinine and paracetamol. AB - The effects of quinine and paracetamol on fever were studied in 21 adult patients with acute uncomplicated falciparum malaria. Quinine alone (n = 7) had no significant effect on fever, whereas paracetamol given 2 h after quinine (n = 7) or 2 h before quinine (n = 7) reduced temperature by a mean of 2.1 degrees C (standard deviation [SD] 0.95) and 2.1 degrees C (SD 0.79) respectively. A temperature reduction of 1 degree C was associated with a mean decrement of 9.7 beats/min (SD 3.3) in the pulse rate. Quinine does not possess useful antipyretic activity. PMID- 7778149 TI - Intraleucocytic malaria pigment and prognosis in severe malaria. AB - The quantity of malaria pigment liberated into the circulation at schizogony reflects the pathogenic sequestered parasite burden in Plasmodium falciparum malaria, and may therefore be a measure of disease severity. Among 300 consecutive adult patients with severe falciparum malaria, the 40 who died had significantly higher proportions of malaria pigment-containing neutrophils on admission (mean = 7.7%, standard deviation (SD) = 5.9%) and pigment-containing monocytes (mean = 8.6%, SD = 5.9%) than did survivors (mean 3.2%, SD = 4.1% and mean 4.8%, SD = 4.6%, respectively) (P < 0.0001). This proved a better indicator of prognosis than the peripheral parasite count. A count of peripheral neutrophils containing visible pigment > or = 5% predicted a fatal outcome with 73% sensitivity and 77% specificity (relative risk 6.2, 95% confidence interval (CI) 3.2-11.8) compared to 60% sensitivity and 57% specificity for parasitaemia > 100,000/microL (relative risk 1.8, 95% CI 1.0-3.3). The peripheral blood count of pigment-containing neutrophils in severe malaria is a rapid, simple, and practical prognostic test. PMID- 7778150 TI - Ethiopian visceral leishmaniasis patients co-infected with human immunodeficiency virus. AB - This communication reports 7 Ethiopian visceral leishmaniasis (VL) patients co infected with human immunodeficiency virus (HIV). The clinical and laboratory findings in 6 patients did not differ from classical VL. All patients had highly elevated anti-leishmanial antibody titres, determined by immunoglobulin G-based enzyme-linked immunosorbent assay; they most probably acquired the Leishmania infection before HIV. Amastigotes were identified in the splenic aspirates of 6 patients and in the lymph node aspirate of the 2 patients whose lymph nodes were examined. The CD4:CD8 lymphocyte ratio was depressed in those patients whose ratio was determined. Most patients showed some initial response to pentavalent antimonial therapy. PMID- 7778151 TI - Ultrasonographical assessment of morbidity in schistosomiasis mansoni in Madagascar: a community-based study in a rural population. AB - Between June and November 1993, a parasitological, clinical and ultrasonographical survey was carried out in the mid west of Madagascar, among the whole population of a village where Schistosoma mansoni was endemic. S. mansoni eggs were found in the stools of 61.8% of the 544 individuals examined; the highest prevalence of infection (85.7%) was observed in the 15-19 years old age group. The most intense infections were recorded in the 10-14 years age group, in which the geometric mean egg count was 265 eggs/g of faeces and 34.3% of the individuals excreted more than 400 eggs/g. The egg count decreased steadily from the age of 15 years. Ultrasonographical examination was performed in 482 inhabitants older than 2 years: 29% of them presented definite schistosome associated liver alterations according to the proposals for staging S. mansoni infection made by the World Health Organization Cairo working group. Stage 3 was never observed in subjects under 30 years old. This is consistent with the need for a long-standing infection before serious lesions occur. A significant relationship between egg count and degree of liver alterations was found only in the 20-29 years age group. PMID- 7778152 TI - Artemether-mefloquine combination in multidrug resistant falciparum malaria. AB - Plasmodium falciparum in Thailand is highly resistant to chloroquine and sulfadoxine/pyrimethamine and there is increasing resistance to the alternative antimalarials, quinine and mefloquine. In eastern Thailand, the cure rates of mefloquine at 750 and 1250 mg were 30% and 55%, respectively. The use of drug combinations may be necessary in areas where drug-resistant parasites exist. 159 male Thai patients in Chantaburi, eastern Thailand, were allocated at random to receive either oral artemether at a single dose of 300 mg on the first day followed by mefloquine 750 mg at 24 h and 500 mg at 30 h (group A), or oral artemether at a single dose of 300 mg on the first day, mefloquine 750 mg at 24 h and placebo at 30 h (group B). The follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42. Most patients in both groups had a rapid initial response to treatment, parasitaemia being cleared within 24 h and fever cleared within 48 h in both groups. The cure rates were 97% and 90%, respectively, for groups A and B. No serious adverse effect was seen in either group; mild and transient nausea, vomiting and loss of appetite were noted. The adverse effects did not differ between the 2 groups. The results suggested that a single oral dose of artemether (300 mg) can markedly improve the cure rate of mefloquine at a dose of 750 or 1250 mg in multiple drug-resistant falciparum malaria. PMID- 7778153 TI - Inhibition of tumour necrosis factor (TNF) production by antimalarial drugs used in cerebral malaria. PMID- 7778154 TI - Antimalarial activity in vitro of Cochlospermum tinctorium tubercle extracts. AB - Resistance of Plasmodium falciparum to current antimalarial compounds has drastically increased during the last few years and is now a major public health problem. We have studied plants traditionally used in Africa against malaria. Extracts of the tubercles of Cochlospermum tinctorium A. Rich, commonly used in Burkina Faso, were tested in vitro on 2 strains of P. falciparum, one (FcB1 Colombia) chloroquine resistant and the other (F32-Tanzania) chloroquine sensitive. Extracts were obtained by infusion and decoction. The 50% inhibitory concentrations (IC50) were determined by measuring [3H]hypoxanthine incorporation and also by microscopical examination which permitted the determination of parasite stages. We obtained similar results with fresh extracts, frozen extracts, and lyophilized extracts of C. tinctorum. IC50 values were of the order of 1-2 micrograms/mL, about one-tenth of those reported for extracts of neem leaves (Azadirachta indica) and about half the values reported for Artemisia annua extracts. PMID- 7778156 TI - Criterion for inclusion in onchocerciasis control programmes based on ivermectin distribution. AB - Data on onchocercal lymphatic and skin lesions from 45 communities located in the West African savanna were analysed to determine if the criterion for inclusion in ivermectin mass treatment based on risk of onchocercal blindness needs to be modified. Only 16 cases of elephantiasis were reported among 10,108 people examined. Other lymphatic lesions were almost exclusively found in people older than 30 years living in villages at risk of onchocercal blindness. Permanent skin lesions also affected older people and were 3 times more frequent in villages at risk of onchocercal blindness. Papular rash and pruritus affected younger people. No evidence was, therefore, found to change the criterion based on risk of onchocercal blindness presently in use in savanna areas. PMID- 7778155 TI - Aminosidine plus sodium stibogluconate for the treatment of Indian kala-azar: a randomized dose-finding clinical trial. AB - This randomized, open sequential design trial was set up to assess the efficacy, tolerability and toxicity of 20 d courses of combined intramuscular aminosidine and sodium stibogluconate at various dosages in patients with newly-diagnosed kala-azar in Bihar, India. Three successive studies of 96 patients each were originally planned with aminosidine administered at 12, 6 and 3 mg/kg/d, respectively. For each aminosidine dosage, patients were randomly assigned to receive sodium stibogluconate at 20, 10 or 5 mg/kg/d of antimony. Ninety-six patients were enrolled and assigned aminosidine 12 mg/kg/d as scheduled. In the subsequent study with aminosidine at 6 mg/kg/d, the trial was interrupted after 40 patients had entered owing to inadequacy of the treatment. With aminosidine 12 mg/kg/d the success rates with sodium stibogluconate at 20, 10 and 5 mg/kg/d were 88%, 71% and 72%, respectively and did not differ significantly. With aminosidine 6 mg/kg/d, 69%, 50% and 46% of patients were cured with the same sodium stibogluconate doses, respectively; again, there was no significant difference between the subgroups. The overall success rate with aminosidine at 12 mg/kg/d (76%) was significantly higher than that with 6 mg/kg/d (55%) (odds ratio = 2.69; 95% confidence interval, 1.11-6.4). Patients improved clinically and the treatments were equally well tolerated. The combination of aminosidine 12 mg/kg/d and sodium stibogluconate 20 mg/kg/d for 20 d appears to be an effective and safe replacement in Bihar for sodium stibogluconate alone for > or = 40 d. PMID- 7778157 TI - A new tool to assess the adulticidal efficacy in vivo of antifilarial drugs for bancroftian filariasis. PMID- 7778158 TI - Antiepileptic drugs and teratogenicity in Nigerians. PMID- 7778159 TI - Serological responses to brucellosis in HIV-seropositive patients. AB - Serial sera from 2 patients infected with the human immunodeficiency virus (HIV) type 1 attending a clinic in Nairobi, Kenya, and with blood cultures yielding Brucella melitensis, were tested by enzyme-linked immunosorbent assay for their serological response (Brucella-specific immunoglobulin (Ig) M and IgG) to Brucella infection. Antibody responses were comparable to those of immunocompetent individuals, one patient showing serology typical of acute brucellosis, the other of chronic brucellosis. Sera from 100 other patients, 65 of whom were HIV-positive, attending the same clinic but whose routine microbiological cultures were negative for Brucella, were tested retrospectively for Brucella-specific antibody. Eight had Brucella-specific IgM and IgG, 6 had IgM only and 21 had IgG only, suggesting relatively high levels of exposure to Brucella in the study cohort. There was no association between Brucella antibody status and HIV status. Brucellosis is probably underdiagnosed in Kenya. Brucella serology may be helpful in the diagnosis of patients with non-specific symptoms in East Africa, regardless of HIV status. PMID- 7778160 TI - Leishmania (Viannia) lainsoni occupies a unique niche within the subgenus Viannia. AB - Leishmania lainsoni has recently been recognized as a new peripylarian species belonging to the subgenus Viannia and the L. braziliensis complex. It has been isolated from its sandfly vector, reservoir host and cutaneous lesions of human patients. Microscopical examination has shown characteristics which are different from those of other members of the L. braziliensis complex. Nuclear deoxyribonucleic acid (DNA) hybridization patterns with a beta tubulin probe and kinetoplast DNA buoyant density measurements show close similarities with other species of the L. braziliensis complex. However, kinetoplast DNA restriction enzyme fragment patterns of L. (V.) lainsoni isolates show similarities to L. mexicana complex species as well as weak cross hybridization. L. (V.) lainsoni is also amplified with L. braziliensis complex specific polymerase chain reaction (PCR) primers but it requires a lower annealing temperature and gives a 300 base pair PCR product. A possible model for the binding of PCR primers to the L. (V.) lainsoni kinetoplast DNA minicircle is proposed. PMID- 7778161 TI - Female genital schistosomiasis: a neglected risk factor for the transmission of HIV? PMID- 7778162 TI - The prognostic value of finding schizonts of Plasmodium falciparum in the peripheral blood. PMID- 7778163 TI - Abdominal tuberculosis. PMID- 7778164 TI - A novel and rapid assay to detect anti-idiotypic anti-OKT3 antibodies. PMID- 7778165 TI - Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation. AB - Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY- >F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day 140. There were no signs of CR in these animals. In the F344-->WKY model, the AR progressed up to stage III-IV (day 21) and maintained for several weeks at stage III. Thereafter, pictures of the lungs showed CR on days 49, 70, and 98. There were significant differences between the two models during the chronic phase, such as interstitial fibrosis (0 +/- 0 vs. 1.8 +/- 1.3, P < 0.005), peribronchiolar fibrosis (0 +/- 0 vs. 3.6 +/- 0.55, P < 0.01), vasculitis (0.2 +/- 0.45 vs. 2.0 +/- 0, P < 0.008), and intimal hyperplasia (0.2 +/- 0.45 vs. 2.6 +/- 0.9, P < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778167 TI - Simultaneous occurrence of rejection and graft-versus-host reaction after allogeneic small bowel transplantation. AB - Small bowel transplantation may be complicated not only by rejection but also by graft-versus-host reaction (GVHR). So far, little is known about the association between these two immunological reactions, partly because of the lack of standardized, reproducible experimental models for such studies. In this work, a rat model in which GVHR and rejection occur simultaneously was established. When transplanting small bowel grafts from BN donors to Lewis recipients and thereafter treating the grafts locally with the immunomodulating substance LS 2616, a clinically visible GVHR occurred on day 6, at the same time the first signs of rejection became visible. The GVHR was confirmed by immunohistochemical staining for MHC class II-positive cells in liver and ear skin biopsy specimens. An obvious quantitative difference in the number of positive cells in both organs was observed when local treatment was compared with oral LS-2616 treatment or with findings in organs from untreated animals. We conclude that GVHR and rejection are not mutually exclusive and thus may occur simultaneously, and that this pharmacological model might facilitate further studies of the impact of GVHR on graft rejection and recipient survival. PMID- 7778166 TI - Inhibition of transplant arteriosclerosis in rat aortic grafts by low molecular weight heparin derivatives. AB - The effects of low molecular weight heparin derivatives with a low anticoagulant activity on transplant arteriosclerosis (TA) in a rat aortic transplant model were investigated. TA was induced by ischemia in the syngeneic transplants and primarily by immunological mechanisms in the allogeneic transplants. Treatment with the heparin derivatives, OAM 71262 or LA-heparin, was administered in a dosage of 250 micrograms/kg/hr by mini-osmotic pumps during 8 weeks. No immunosuppressive regimen was given to the recipient rats in either model. All rats were killed 8 weeks after aortic grafting. The grafts were examined for intimal and medial changes using an image analysis system. Heparin derivatives had a beneficial effect on both the intimal thickening and the medial injury in the syngeneic transplants, but not in the allogeneic grafts. In the syngeneic LA heparin treated grafts, the thickness of the intima was less than that in the syngeneic control grafts (P < 0.05). In the syngeneic transplants, a significant increase was observed in the media after treatment with OAM 71262 (P < 0.01) as well as those with LA-heparin (P < 0.001). In the syngeneic grafts treated with both heparin derivatives, a significant reduction in the antigen expression of alpha-actin-containing smooth muscle cells in the intima, transforming growth factor-beta 1 both in the media and adventitia, and platelet-derived growth factor-beta receptors in the adventitia was observed immunohistochemically. In summary, low molecular weight heparin derivatives with low anticoagulant activity partially inhibited ischemia-induced syngeneic TA, whereas no such effect could be demonstrated in nonimmunosuppressed recipients with allogeneic grafts. PMID- 7778168 TI - Protection by pentoxifylline against normothermic liver ischemia/reperfusion in rats. AB - Previously, pentoxifylline treatment of graft recipients was shown to protect against liver graft failure from storage/reperfusion injury after orthotopic rat liver transplantation. To determine whether pentoxifylline also protects against normothermic ischemia/reperfusion injury to liver, we induced lobar ischemia in rats followed by reflow and partial hepatectomy of the noninvolved liver. In rats receiving pentoxifylline 2 hr before surgery and then twice daily for 5 days, the 1-week survival rate more than doubled from 25% to 67% (P < 0.05). Liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) in the serum and liver necrosis evaluated histologically were also significantly reduced in the pentoxifylline-treated rats (P < 0.01). Hepatic ischemia/reperfusion increased leukocyte infiltration into the lungs, and pentoxifylline tended to reduce this lung injury (P = 0.06). These results show that pentoxifylline treatment reduces hepatic injury and improves survival after normothermic ischemia and reperfusion. PMID- 7778169 TI - Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. AB - Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft. PMID- 7778171 TI - Cyclosporine (Sandimmun) in cadaveric renal transplantation. Ten-year follow-up of a multicenter trial. European Multicentre Trial Group. PMID- 7778170 TI - Randomized clinical trial of antithymocyte globulin induction in renal transplantation comparing a fixed daily dose with dose adjustment according to T cell monitoring. AB - Antithymocyte globulin (ATG) has been used successfully for induction therapy as well as for treatment of established allograft rejection. However, this therapy has often been associated with problems of overimmunosuppression and increased costs. In a randomized clinical trial, we compared the immunosuppressive benefits, complication rates, and treatment costs when ATG is given as a fixed daily dose or when the dose is adjusted daily according to its biologic effects on T cells. Forty-five recipients of cadaver renal allografts were randomized into two groups. In group 1 (n = 23), ATG (ATGAM) was administered in variable doses to maintain the absolute number of peripheral CD3 T cells at 50 100/microliters. In group 2 (n = 22), ATG was given at a fixed dose of 15 mg/kg/day. All patients received azathioprine and prednisone. ATG was discontinued at 7-14 days when cyclosporine was introduced. In both groups, CD2, CD3, CD4, CD8, and CD19 cells were measured by flow cytometry and the levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM 1, IL-6, Il-7, and IL-10 were measured by ELISA. In group 2, the levels of all T cell subsets were profoundly suppressed. In group 1, the number of CD3 and other T cells was maintained at about 100 cells/microliters, while the CD19 T cells remained unsuppressed. Cytokine levels were greatly suppressed in group 2 compared with group 1, except for IL-10 levels, which remained elevated in the latter group. Patient survival, graft function, and the incidence of acute and recurrent rejections were similar in the two groups. Bone marrow suppression and infective complications were greater in group 2 than in group 1. The mean daily dose and the total quantity of ATG used in group 1 were significantly smaller than in group 2, resulting in a savings of $2,398.00 per patient per treatment. It is concluded that monitoring of ATG by its biologic effects on T cells is a rational and safe method of regulating the dose of this important agent; in this way, it is possible to reduce the total amount of the drug given to patients with consequent reduction in undesirable complications as well as in the cost of treatment without loss of immunosuppressive benefits. PMID- 7778172 TI - Critical role of interleukin 4 in the induction of neonatal transplantation tolerance. AB - Neonatal injection of semiallogeneic cells is known to promote differentiation of donor-specific CD4+ T cells into TH2-like cells in the peripheral lymphoid organs. We reasoned that the propensity of neonatal T cells to synthesize high levels of IL-4 might be involved in this polarization of the alloreactive response and thereby in the development of neonatal transplantation tolerance. First, analysis of cytokine gene expression in lymph nodes after neonatal injection of 10(7) (A/J x BALB/c)F1 cells in BALB/c mice indicated that IL-4 but not IL-2 is rapidly produced by CD4+ cells after allogeneic challenge in vivo. To determine whether the early production of IL-4 was involved in the establishment of allotolerance, BALB/c mice neonatally injected with (A/J x BALB/c)F1 spleen cells received on days 1 and 3 after birth 1 mg of anti-IL-4 mAb (11B11) or the same amount of control mAb. When grafted with A/J skin at 4 weeks, 88% of mice treated with control mAb retained their graft for more than 50 days, whereas rejection occurred within 30 days in 93% of mice treated with anti-IL-4 mAb. Analysis of T cell functions after in vitro restimulation with A/J spleen cells indicated that early IL-4 neutralization did not prevent donor-specific CTL unresponsiveness but allowed the emergence of alloreactive T cells secreting increased levels of IL-2 and IFN-gamma. We conclude that early production of IL-4 is critical for the establishment of neonatal transplantation tolerance in this strain combination, which has disparities across the entire H-2 region. PMID- 7778173 TI - Prevention of bone marrow and cardiac graft rejection in an H-2 haplotype disparate mouse combination by an anti-LFA-1 antibody. AB - The aim of the present study was to compare the preventive effect of a nondepleting monoclonal antibody specific for the LFA-1 alpha chain (CD11a) on the rejection of bone marrow, vascularized cardiac, and nonvascularized skin grafts in the same haplotype-disparate mouse strain combination. A 7-day treatment with a total dose of 0.5 mg of anti-LFA-1 antibody (H-129) had no effect on the rejection of BDF1(H-2b/d) skin grafts by CDF1 (H-2k/d)-treated mice. In contrast, the same treatment regimen significantly prolonged the survival of BDF1 cardiac allografts in CDF1 mice: 7 out of 10 mice had a functional graft after 70 days, whereas all control mice had rejected their graft by 11 days. Nevertheless, cardiac allografts were ultimately rejected. In contrast, infusion of anti-LFA-1 antibody was able to promote definitive engraftment of T-depleted BDF1 marrow in 9 gray-irradiated CDF1 recipients: in surviving mice, engraftment increased from 10% in controls to 78% in antibody treated recipients. In mice that tolerated their cardiac graft for more than 70 days, there was a slight delay in the rejection of donor skin graft but no in vitro evidence of tolerance. In contrast, mice with successful marrow engraftment did not reject donor skin graft and failed to mount proliferative and cytotoxic responses against donor alloantigens, whatever the percentage of engrafted donor leukocytes. These results indicate that a nondepleting anti-LFA-1 antibody can efficiently protect against rejection of MHC-incompatible heart and bone marrow. The protective effect of anti-LFA-1 antibody was associated with the induction of T cell tolerance toward donor antigens after bone marrow transplantation. PMID- 7778175 TI - Variation in the level of xenoantigen expression in porcine organs. AB - Hyperacute rejection of vascularized porcine to primate xenografts is initiated by the binding of xenoreactive natural antibodies to donor endothelium. We tested the hypothesis that the level of xenoantigen expression varies in the population of potential porcine donors and may determine the amount of binding of xenoreactive natural antibodies to a porcine organ perfused by xenogeneic blood. Two hundred ninety pigs were studied using an inhibition ELISA that quantitated the xenoantigen level on porcine platelets. Based on this assay, the levels of xenoantigen expression in the population adhered to a normal distribution. Kidneys from pigs found to express high antigen levels and kidneys from pigs found to express low antigen levels were perfused with baboon blood using an extracorporeal circuit. In multiple experiments, a significant difference was observed in the amount of xenoreactive natural antibody adsorbed by high antigen versus low antigen organs. Normalizing for the weight of the perfused organs and for levels of natural antibody in individual baboons, high antigen organs adsorbed 3.6 +/- 1.3 U of xenoreactive natural antibody/g and low antigen organs adsorbed -0.8 +/- 1.0 U of xenoreactive natural antibody/g (P < 0.002). Immunopathology of tissues from the perfused organs demonstrated more deposition of IgM and C4 in high than in low xenoantigen organs. The quantitative relationship between binding of xenoreactive natural antibodies to platelets and to whole organs suggests that platelets are a valid representation of endothelial cell antigen expression in vivo. Despite the probable importance of Gal alpha(1 3)Gal as an epitope recognized by xenoreactive natural antibodies, differences in the binding to platelets or to organs of the GS-I-B4 lectin that recognizes that sugar had no correlation with the differences in binding of IgM to these tissues. Variation in expression of xenoantigen may be exploited to selectively breed donors for xenotransplantation that are less susceptible to attack by xenoreactive natural antibodies. PMID- 7778174 TI - Inadequate antibody response against respiratory viral infection in long surviving rat lung allografts. AB - Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants. Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impaired in 3 groups of rats with: (1) BN-to-LEW allogeneic lung transplants, (2) LEW-to-LEW syngeneic lung transplants, and (3) nontransplanted LEW lungs. All rats (including those with nontransplanted, normal lungs) were treated with cyclosporine on days 2 and 3 after operation; this treatment is adequate to induce permanent graft acceptance of the allografts. Six months after transplantation, viral infections with Sendai virus (parainfluenza type I) were induced intratracheally. At day 0, immediately before infection, and at days 4, 7, 21, and 56 after infection, 4 rats in each group were killed for histological evaluation of the lungs. The number of antibody-positive cells in the bronchus-associated lymphoid tissue (BALT) in the lungs and in the spleen, and presence of the virus in the lungs were determined by immunohistology. Serum antibody titers were followed for 56 days after infection. The allogeneically transplanted lungs failed to respond adequately against the virus: the number of antibody-positive cells in the BALT did not increase after infection, serum antibody titers were hardly detectable, and virus was present in the airways of the lungs up to day 21 after infection. In contrast, in the syngeneically and nontransplanted lungs, the number of antibody-forming cells in the BALT increased steeply until day 7, serum antibody titers rose until day 14, and virus could be detected only on day 4 after infection. This study shows that in rat lung allografts, both the local antibody production in the BALT and the systemic antibody response against a respiratory viral infection are inadequate. As a consequence, the virus is present longer in these allografted lungs and can exert its damaging effect over a longer period of time. These results may explain why lung transplants are so susceptible to viral infections. PMID- 7778176 TI - X-irradiation of the thymus is not required for the induction of cyclosporine induced autoimmunity. AB - The thymus-dependent model of cyclosporine-induced autoimmunity (CsA-AI) in the Lewis rat requires a lethal total body X-irradiation and rescue with syngeneic or autologous bone marrow and cyclosporine (CsA) administration for at least 4 weeks; two to three weeks after cessation of CsA, the animals develop a graft versus-host-like disease. The obligatory role of the thymus in the etiology of CsA-AI has been established unequivocally, but the way in which disease is thymus dependent is a topic of debate. In the present study we demonstrate that the model of CsA-AI requires the presence of a thymus for at least 2 weeks after total body irradiation and CsA administration, but that X-irradiation of the thymus itself is not necessary to bring about disease. Transplantation of neonatal thymus shows in addition that in the absence of X-irradiation of the thymus, CsA therapy is required to generate autoreactive cells, but that disease occurs only if peripheral autoregulatory cells are eliminated by X-irradiation. PMID- 7778177 TI - Human lymphocytotoxic monoclonal autoantibodies from a highly sensitized renal dialysis patient. AB - A panel of 5 human monoclonal autolymphocytotoxic antibodies (IRM-3, IRM-4, IRM 7, IRM-8, and IRM-10) of the IgM class was established from a highly sensitized renal dialysis patient (IRM), by the generation of mouse-human heterohybridomas. This panel was screened for reactivity against foreign and autoantigens by ELISA, and for reactivity against different tissue sections and HEp-2 slide preparations by indirect immunofluorescence. Cytotoxicity screening of heterohybridoma supernatants gave broad panel reactivity profiles, being cytotoxic against B cells from patient IRM and also against most B cells tested and less reactive with chronic lymphocytic leukemia B cells; T cells were the least sensitive target. Immunoblotting showed that monoclonal IRM displayed some heterogeneity in their binding profiles, although all of them recognized a cellular structure of 26 kDa. None of the heterohybridoma cell lines exhibited cytoplasmic nor surface staining with an anti-CD5 mAb. Results obtained showed that all the autolymphocytotoxic mAbs generated were also able to react against certain nuclear and cytoplasmic self-structures as well as foreign compounds. Monoclonal antibody IRM-7 and, to a lesser degree, IRM-10 exhibited multispecific properties similar to those observed for polyreactive or natural antibodies. PMID- 7778178 TI - Immunological fate of Schwann cell-populated acellular basal lamina nerve allografts. AB - Acellular basal lamina allografts are known to exhibit reduced immunogenicity, but the extent of host axonal regeneration through such grafts is reduced in comparison to the cellular isografts. The present study was designed to determine both the ability of cultured Schwann cells to populate acellular allografts, and the effects of Schwann cells on immunogenicity and regenerative potential. Isogeneic and allogeneic Schwann cell-populated acellular allografts of 2.0 cm length were used to repair a surgically created gap in the host rat peroneal nerve. Transplanted nerves were analyzed at 1, 2, 4, and 8 weeks later to determine their fate and ability to support axonal regeneration. Acellular allografts cocultured with isogeneic Schwann cells survived and supported axonal regeneration through them. In contrast, acellular allografts cocultured with allogeneic Schwann cells underwent rejection and were unsuccessful. The results show that cultured Schwann cells continue to exhibit immunogenicity and are a critical factor in allograft survival. It is thus important to use host-matched (isogeneic or autologous) Schwann cells to populate acellular basal lamina grafts in order to enhance their axonal growth-supporting function. PMID- 7778179 TI - Comparison of the effects of enalapril and theophylline on polycythemia after renal transplantation. AB - Posttransplant erythrocytosis (PTE) is a potentially serious complication for which (apart from phlebotomy) two alternative treatments have been proposed: theophylline (Theo) and angiotensin-converting enzyme inhibitors. We investigated 28 patients with PTE, who were assigned to 3 matched groups. Group 1 (10 patients) received 10 mg of Enalapril (Ena)/day. After 2 months, mean hematocrit (Ht) had dropped from 0.57 (range 0.52-0.62) to 0.45 (0.34-0.49). Ena was stopped and, after a period of 3.8 +/- 0.3 months, Ht had risen again to baseline values (0.56, range 0.52-0.61) in 8 of them. These 8 patients were then given 5 mg/day Ena. Ht decreased more slowly, and after 3 months reached a mean of 0.49 (0.44 0.54). Group 2 (9 patients) received 600 mg/day Theo in 2 doses. After 2 months, Ht had decreased from 0.56 (0.52-0.61) to 0.52 (0.46-0.63), but in 5 patients, Ht remained above 0.51. After 1 month discontinuation of treatment, PTE persisted in 7 patients. These patients were given 10 mg/day Ena, whereupon Ht decreased from 0.55 (0.52-0.64) to 0.46 (0.40-0.53) after 2 months and to 0.41 (0.33-0.47) after 3 months. Group 3 did not receive medical treatment. After 3 months, PTE persisted in 8 out of the 9 patients and remained unchanged during the following 3 months. Mean values for Ht were: baseline, 0.55 (0.52-0.58); after 3 months, 0.56 (0.53-0.59); and after 6 months, 0.55 (0.52-0.60). We conclude that Ena is superior to Theo in the treatment of PTE. There were no resistant patients, but individual sensitivity differs. Its effect is dose dependent, reversible, and reproducible. Excessive Ht decrease may occur; thus, doses should be titrated individually. PMID- 7778180 TI - alpha-Interferon-induced rejection of a hepatitis C virus-infected liver allograft tolerated with a low dosage immunosuppressive regimen. PMID- 7778181 TI - Lack of sustained efficacy of combination ganciclovir and foscarnet for hepatitis B virus recurrence after liver transplantation. PMID- 7778182 TI - Renal transplantation without chronic immunosuppression after T cell-depleted, HLA-mismatched bone marrow transplantation. PMID- 7778183 TI - American Society of Histocompatibility and Immunogenetics Crossmatch study. PMID- 7778184 TI - Antigen-dependent activation of T helper cell subsets by endothelium. PMID- 7778185 TI - Effects of interleukin 2 on leukemia development after bone marrow transplantation in AKR/J mice. PMID- 7778186 TI - Inositol 1,4,5-trisphosphate receptors, secretory granules and secretion in endocrine and neuroendocrine cells. AB - Recent studies have revealed the presence of inositol 1,4,5-trisphosphate receptors in the secretory granules of endocrine and neuroendocrine cells. This distribution suggests that inositol 1,4,5-trisphosphate-regulated release of granule stores of Ca2+ might facilitate the secretory process. In addition, inositol 1,4,5-trisphosphate receptors might participate directly in the biogenesis of secretory granules. The presence of inositol 1,4,5-trisphosphate receptors in synaptic nerve terminals raises the possibility that they might also be involved in the control of neurotransmitter release. PMID- 7778187 TI - Mutations in the cell adhesion molecule L1 cause mental retardation. AB - Recently, studies in the usually disparate fields of human genetics and developmental neurobiology have converged to reveal that some types of human mental retardation and brain malformations are due to mutations that affect the neural cell adhesion molecule L1. L1 has a very complex biology, interacting with a variety of ligands, and functioning in migration of neurons and growth of axons. Over the past few years, it has also become clear that L1 is able to influence intracellular second messengers. The identification of a number of different mutations in L1, some of which alter the extracellular portion of the molecule, and others that change only the cytoplasmic tail, confirm that L1 is a crucial player in normal brain development. The information gained from genetic analysis of human L1 is giving new insights into how L1 functions in the formation of major axon pathways, but it also raises unanticipated questions about how L1 participates in the development of cortical and ventricular systems. PMID- 7778188 TI - Radical AGEing in Alzheimer's disease. AB - The pathological presentation of Alzheimer's disease, the leading cause of senile dementia, involves regionalized neuronal death and an accumulation of intracellular and extracellular filamentous protein aggregates that form lesions termed neurofibrillary tangles and senile plaques, respectively. Several independent parameters have been suggested as the primary factor that is responsible for this pathogenesis, including apolipoprotein epsilon genotype, hyperphosphorylation of cytoskeletal proteins, or metabolism of amyloid beta. However, at present, no one theory explains adequately the host of complex biochemical and pathological facets of the disease. Recent findings suggest that age-related increases in oxidative stress and protein glycation either individually, or more probably in a synergistic manner, could, exclusive of the other theories or in concert with them, account for all aspects of Alzheimer's disease. PMID- 7778189 TI - Synaptotagmin controls and modulates synaptic-vesicle fusion in a Ca(2+) dependent manner. AB - Although numerous electrophysiological and biochemical studies have defined many of the properties of the putative Ca2+ receptor for exocytosis at the synapse, the molecular mechanisms that couple influx of Ca2+ and release of neurotransmitter have remained elusive. Several proteins have emerged recently as putative Ca2+ sensors. Interestingly, one of these proteins, synaptotagmin, shares many properties with the putative Ca2+ receptor. Recent genetic experiments in Caenorhabditis elegans, Drosophila and mouse have provided important insights about synaptotagmin's role in neurotransmitter release. These experiments, combined with electrophysiological and biochemical studies, suggest that synaptotagmin is a key Ca2+ sensor, converting the ubiquitously used cellular secretory pathway into a Ca(2+)-regulated exocytotic pathway. PMID- 7778190 TI - Ca2+ and secretory-vesicle dynamics. AB - Exocytosis in neurones and neuroendocrine cells is triggered by an increase in the cytosolic concentration of Ca2+, and is followed by endocytotic membrane retrieval. Electrophysiological studies have characterized the nature of the Ca2+ signal that is required for exocytosis, and have defined the Ca(2+)-dependent steps in exocytotic and endocytotic vesicle cycling. In parallel, biochemical approaches have led to the discovery of a range of proteins that appears to function in synaptic- and secretory-vesicle dynamics. The nature of the Ca(2+) binding proteins, and how they interact with the identified components of the exocytotic and endocytotic machinery, remain key unresolved issues. However, it is apparent that exocytosis involves multiple Ca(2+)-binding proteins with different affinities, and that the Ca2+ sensor involved in the final membrane fusion step has different affinities for Ca2+ in synapses and neuroendocrine cells. PMID- 7778191 TI - From contact to connection: early events during synaptogenesis. AB - When neuronal processes first come into contact, chemical synapses can form rapidly. Many neurons synthesize synaptic machinery through intrinsic programs before cell-cell interactions. During the formation of chemical synapses, contact with appropriate targets has been found to trigger intracellular signals that induce the assembly of pre-existing synaptic machinery. We propose that 'promiscuous' neurons secrete transmitter before contacting their targets, and form over-abundant synapses, which undergo additional activity-dependent refinement; 'selective' neurons, which retain their original connectivity, require concerted retrograde and anterograde signaling to ensure their correct matching. PMID- 7778192 TI - Helicobacter pylori infection. PMID- 7778193 TI - Integrated health programmes. PMID- 7778194 TI - Evaluation of performance of reused HIVCHEK 1 + 2 test blocks which have shown negative result: a reliable method for rural hospital? AB - The performance of the reusing of test membranes which have been used previously for negative tests for the detection of antibody to HIV (HIVCHEK 1 + 2 of Ortho Diagnostic Systems, Paris, France) was evaluated under field conditions. The sensitivity and specificity of the reusing strategy compared with a HIV determination obtained by using new HIVCHECK 1 + 2 tests were 89.1% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 91.5%. The authors conclude that the reduction in sensitivity of the reusing strategy in comparison with the use of new tests makes this strategy ethically unacceptable for the detection of HIV infection in blood donors. On the other hand, the reusing strategy could be very useful for diagnostic purpose and for epidemiological HIV surveillance in resource-poor countries. PMID- 7778195 TI - The partograph in community obstetrics. PMID- 7778196 TI - Hypokalaemic paralysis precipitated by working in hot weather. AB - Twenty-two cases of hypokalaemic paralysis seen over the past 7 years, are presented here. They included five Chinese, five Bangladeshis, six Arabs, four Philippinos and two Indians. The number of cases related to the population of each nationality in our area showed that the Chinese had the biggest number of cases in relation to their population in our area, followed by Philippinos then Bangladeshis. All patients were men admitted in the hot season, dehydrated and not able to walk. It seems that dehydration was an important precipitating factor in our cases. Although family history was positive in one patient, apart from four thyrotoxic patients, the others were apparently healthy. Patients improved dramatically with i.v. potassium and rehydration. Four patients were readmitted with the same picture. PMID- 7778197 TI - Incidence of duodenal ulcer and its surgical management in a teaching hospital in Bangladesh. AB - Duodenal ulcer patients with or without complications admitted in the surgical departments of Rajshahi Medical College Hospital (RMCH) during the period of 13 years from 1980-1992 were studied retrospectively. Duodenal ulcer accounted for 10/1000 admission and five operations per week. Of the 1623 patients with uncomplicated ulcer, only 623 needed surgical treatment. However, all of the 1599 who presented with pyloric stenosis, 1047 with peritonitis due to perforation, and 13 with hematemesis were operated upon. This study confirms previously published reports of high incidence of duodenal ulcer admissions in the hospital but shows a diminishing number in the uncomplicated cases requiring surgery. PMID- 7778198 TI - Case management quality assessment in rural areas of Papua New Guinea. AB - A study was carried out to assess the quality of case management of malaria, malnutrition, diarrhoea and acute respiratory tract infections in children in rural primary health services in Papua New Guinea. In particular, the study focused on the knowledge and skills of different categories of rural health workers (HW) in history taking, examination, diagnosis, treatment and patient education. Quality criteria were defined and health centre (HCW) and aidpost workers' (APWs) knowledge and practices were assessed. Primary health workers' (PHW) knowledge of case management was weak, but in all cases better than their actual practice. History taking and examination practices were rudimentary. HWs tended not to make or record diagnoses. Treatment knowledge was often incorrect, with inappropriate or insufficient drugs prescribed, being worst at aidpost level. These findings raise serious questions about the effectiveness of providing health services through small, isolated health units. Far greater attention must now be directed to focus on the institutionalization of problem based training, continuous supportive supervision and maintenance of clinical skills and provision of essential drugs, supplies and equipment to ensure that rural health workers (RHW) can provide sound care. PMID- 7778199 TI - Health management and action research: bringing them together for the district medical officer. PMID- 7778200 TI - Successful treatment of antimony-resistant visceral leishmaniasis with liposomal amphotericin B (L-AmpB-LRC) in a child. PMID- 7778201 TI - Sheehan's syndrome presenting as a psychosis. PMID- 7778202 TI - Pulmonary blastomycosis. PMID- 7778203 TI - Perforation in acute acalculus Salmonella cholecystitis. PMID- 7778204 TI - Human bite injuries to the nose. PMID- 7778205 TI - New diagnostic tools to improve tropical primary health care: the Jabric multipurpose manual centrifuge. PMID- 7778206 TI - Perinatal health--a hospital staff survey in Nepal. PMID- 7778207 TI - Dyspepsia and Helicobacter pylori infection in rural south west Cameroon. PMID- 7778208 TI - Herniation of ureter in inguinal hernia. PMID- 7778209 TI - A simple method for the removal of retained urinary balloon catheters. PMID- 7778210 TI - Transport and referral of medical inpatients in Blantyre, Malawi. PMID- 7778211 TI - Neuroparalytic complications after anti-rabies vaccine (inactivated nervous tissue vaccine) PMID- 7778212 TI - The feasibility of repetitive courses of high-dose continuous intravenous infusion interleukin-2 and subcutaneous alpha-interferon with polychemotherapy in advanced malignant melanoma. AB - AIMS AND BACKGROUND: A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rIL-2) and subcutaneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficacious way to sequence this kind of treatment for advanced malignant melanoma. STUDY DESIGN: Patients who had measurable metastatic melanoma, a Karnofsky performance status > or = 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m2 i.v. day 1 in alternating cycles; DTIC, 220 mg/m2 i.v. days 1, 2 and 3; CDDP, 25 mg/m2 i.v. days 1, 2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18 x 10(6) IU/m2/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha interferon (IFN) s.c. 3 x 10(6) U day 12, 6 x 10(6) U day 14, 9 x 10(6) U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9 x 10(6) U days 2, 5, 7, 9, 12, 14, 16, 19, 21, 23, 26, and 28). Two consecutive cycles were planned until response evaluation. RESULTS: Three patients were treated according with the protocol; none of them was able to respect the planned dose-intensity schedule. The given dose intensity/planned dose intensity ratios were as follows: DTIC, 0.74 (range, 0.70-0.80); CDDP, 0.77 (0.72-0.80); BCNU, 0.77 (0.72-0.80); rIL-2, 0.65 (0.36 0.80); alpha-IFN, 0.01 (0-0.03); tamoxifen, 1.0. Systemic side effects of rIL-2 and myelotoxicity were the main reasons for treatment delay and/or dose reduction, and for the long period of hospital care. CONCLUSIONS: We conclude that the treatment schedule is not feasible. However, since we believe that combined chemo-immunotherapy is a potentially active treatment in metastatic malignant melanoma, we have modified it in order to make it more feasible and consequently efficacious. PMID- 7778213 TI - Combination of epirubicin and lonidamine for treatment of advanced breast cancer. AB - AIMS AND BACKGROUND: In vitro and in vivo studies have shown that lonidamine potentiates the cytotoxic effect of anthracyclines in simultaneous and sequential combination. On the basis of such evidence, we evaluated the activity and toxicity of a combination of epirubicin plus lonidamine in advanced breast cancer. METHODS: Between January 1991 and November 1993, 33 patients with advanced breast cancer, age < 75 years and PS < 2, were treated with epirubicin (75 mg/m2 i.v. on day 1, every 3 weeks), plus lonidamine (450 mg/day orally from day 1 continuously until disease progression). RESULTS: Thirty patients were evaluable for response: 4 achieved complete response (13%) and 8 partial response (27%) (total response rate = 40%), 6 (20%) had stabilization of disease, and 12 (40%) progression of disease. The median duration of response was 10 months (range, 4-24+ months). This scheme was tolerated, with a mild additional toxicity related to lonidamine: only WHO grade III myalgia in 1 patient (3%) and epigastralgia in 3 patients (9%). CONCLUSIONS: Although some patients seem to have benefited from the combination at the dose levels of the drug used in the study, the therapeutic advantages of addition of lonidamine remain unclear. PMID- 7778214 TI - Indium-111-DTPA-octreotide scintigraphy modulation by treatment with unlabelled somatostatin analogue in small-cell lung cancer. AB - AIMS AND BACKGROUND: Small-cell lung cancer (SCLC) tissue expresses somatostatin receptors and can be visualized by means of the indium-111-labelled somatostatin analogue DTPA-D-Pheoctreotide. The aim of the study was to investigate whether treatment with a cold somatostatin analogue can affect the imaging of somatostatin receptor scintigraphy. METHODS: Three patients with SCLC were treated with 200 micrograms of cold octreotide three times a day subcutaneously for 7 days. Whole body and planar scintigraphy was performed before and after the treatment. RESULTS: 111In-DTPA-octreotide uptake was increased in cancer lesions, whereas fixation in normal tissues (liver, spleen, kidneys) decreased. CONCLUSIONS: This is the first demonstration of an enhancement of SCLC imaging following unlabelled somatostatin analogue administration. Similar results have been described by other authors in a limited number of carcinoid tumors. PMID- 7778215 TI - Immunoglobulin heavy chain gene rearrangement in B-cell non-Hodgkin's lymphomas detected by the polymerase chain reaction. AB - AIMS AND BACKGROUND: Immunoglobulin heavy chain gene rearrangement serves as a marker of clonality and cell lineage in B-cell lymphoproliferative disorders. In this study we used the polymerase chain reaction (PCR) to detect clonal rearrangements of the immunoglobulin heavy chain gene in a group of patients with B-cell lymphomas. METHODS: DNA was extracted from frozen tissue of 40 B-cell non Hodgkin's lymphomas and subjected to PCR amplification using primers that recognize conserved sequences of the variable and joining regions of the immunoglobulin heavy chain gene. RESULTS: Monoclonal rearrangements were detected in 23 of 40 malignant B-cell lymphomas. No clonal rearrangements were detected in the 10 control cases. CONCLUSIONS: We conclude that this PCR-based technique may provide a simplified and rapid approach for the detection of clonal immunoglobulin heavy chain gene rearrangements in B-cell lymphomas without recourse to Southern blotting, which can be reserved for cases in which PCR is negative. PMID- 7778216 TI - Differences in blood glutathione levels of patients with advanced or localized carcinoma. AB - AIMS AND BACKGROUND: The increased level of blood glutathione (GSH) is an important biochemical feature in animal epithelial tumor. The aim of this study was to investigate the blood GSH concentrations in well characterized cancer patients and healthy volunteers. METHODS: Two different groups of carcinoma cases were used. The first group consisted of 15 blood samples drawn from disseminated gastric adenocarcinoma patients, and the second group comprised 15 samples obtained from localized or locally advanced skin carcinoma cases without lymph node metastasis. GSH and hemoglobin concentrations were measured by using the method of Beutler et al. RESULTS: The mean blood GSH in patients who had advanced malignant disease was 129.13 +/- 7.49 mg/dl and in patients who had localized cancer was 96.24 +/- 3.90 mg/dl. These results indicate that the blood GSH level is 31% higher in localized carcinoma cases and 78% higher in metastatic disease than those of controls. Blood GSH concentrations were expressed on the basis of blood volume and also on hemoglobin content. Similar results were calculated with either mode of expression. CONCLUSION: By comparing the two groups of patients, we found that higher blood GSH concentration was correlated with metastatic growth. PMID- 7778217 TI - Breast carcinoma with osteoclast-like giant cells: immunohistochemical and ultrastructural study of a case and review of the literature. AB - We describe an unusual case of infiltrating ductal carcinoma, not otherwise specified, containing numerous benign stromal osteoclast giant cells (OGCs). Macroscopically, the tumor appeared as a well-outlined dark brown mass and was initially interpreted as a benign lesion on the mammograms. OGCs were uniformly distributed in the tumor and were found in vascularized, hemorrhagic stroma often abutted on the nests of tumor cells. Electron microscopy supported a histiocytic origin of the OGCs, but immunohistochemistry failed to confirm the observation. The patient was alive and well 30 months following the operation. A review of the literature concerning breast carcinoma with OGCs is also presented. PMID- 7778218 TI - Solitary brain metastases from thyroid carcinoma: study of 6 cases. AB - AIMS AND BACKGROUND: Although systemic metastases from thyroid cancer are relatively frequent, they rarely affect the nervous system and only exceptionally originate from well-differentiated carcinoma. METHODS: The authors describe 6 cases of solitary brain metastases from thyroid carcinoma, well-differentiated in 3 cases and anaplastic in the other 3 cases. RESULTS: Four patients were females and 2 males (M:F ratio, 1:2); average age was 51 yrs (range 48-56). On average, the interval between diagnosis of the thyroid tumor and appearance of the metastasis was 2.8 years (range 1-12 years) and was shorter in the anaplastic forms (1.2 versus 4.4 years). Average survival was 15 months (range 6-48 months); in particular, average survival was longer in patients with well-differentiated carcinoma (9 vs 21 months) as also in those who did not present other metastatic sites (6 vs 24 months). Death was due to systemic progression of the disease in 4 cases and to brain-relapse in the other 2 cases. CONCLUSIONS: Surgery, radioactive iodine (where uptake is demonstrable), and radiotherapy are the main therapies available for metastases from thyroid carcinoma. However, survival of patients appears to be modified by the type of treatment performed. PMID- 7778219 TI - Lymphoepithelioma-like carcinoma of the lung. Two cases diagnosed in Caucasian patients. AB - Lymphoepithelioma-like carcinoma is a non-nasopharyngeal undifferentiated carcinoma with prominent lymphoid infiltration. Ten cases arising in the lung have been reported so far; seven cases were diagnosed in Orientals, with the Epstein-Barr virus (EBV) genome demonstrated in neoplastic cells by in situ hybridization; the remaining three cases affected Caucasian patients and showed no evidence of hybridized viral genome. The present study describes two additional cases of lymphoepithelioma-like carcinoma of the lung in Caucasians, with reference to the differential diagnosis versus other thoracomediastinal malignancies. The neoplastic nuclei, blast-like in appearance, together with the immunohistochemical profile of the neoplastic cells (positivity for cytokeratins, and negativity for CD antigens, S100 protein, placental alkaline phosphatase, and neuroendocrine markers) represent the basic pathologic features of a lymphoepithelioma-like carcinoma and allow its recognition even on small bioptic fragments, in which the typical biphasic, Regaud-like morphology might be inapparent. In accordance with the previously reported cases of pulmonary lymphoepithelioma-like carcinoma in Caucasian patients, the present study found no evidence of the Epstein-Barr virus genome in neoplastic cells with in situ hybridization. PMID- 7778220 TI - Neuroendocrine carcinoma of the skin: a case report of "multiple neuroendocrine carcinoma" onset and long-term remission after chemotherapy. AB - We herein report a case of "multiple neuroendocrine carcinoma" onset, with a torpid course, metastasis in the left breast, and an initial considerable sensitivity to the chemotherapy. We conclude that a re-evaluation of the studies on this neoplasia carried out to date is needed, in order to identify new regimens, which increase the complete response rates and their duration. PMID- 7778221 TI - Inflammatory pseudotumor of the liver. A report of two cases with unusual histologic picture. AB - Two cases of inflammatory pseudotumor (IPT) of the liver are reported. Clinical presentation was vague and aspecific. Laboratory tests and data from imaging techniques provided no specific information on the actual nature of the lesions and were misleading, suggesting a malignant lesion in one patient and a complicated hydatid cyst in the other. On gross examination, the tumors appeared yellowish ore grey-yellow in color, with a firm cut surface and well circumscribed from the surrounding parenchyma, although a true capsule was not evident. Variability in the histological pattern was also observed, even though the major finding was in both cases an admixture of lymphocytes, plasmacells, granulocytes and monocytes. Lymphocytes were immunohistochemically heterogeneous; monocytes showed in one case large hyperchromic atypical nuclei, confirming the previously, reported possibility that some cases of IPT may be mistaken for sarcomas. Further evidence is added in support of the hypothesis that some liver IPT may result from the evolution of cholangitic abscesses. PMID- 7778224 TI - Diagnostic accuracy of primary liver cancer: implications for cancer registration. AB - AIMS AND BACKGROUND: We evaluated some standardized criteria for classifying incident cases of liver cancer into either primary liver cancer (PLC) or unspecified liver cancer (ULC) on the basis of the diagnostic examinations performed and their results. METHODS: A pilot hospital-based study (98 cases) was carried out in Verona, northern Italy, with the main aim of assessing the feasibility of the method. The same procedures were subsequently applied in a population-based study (349 cases) in Brescia, northern Italy. RESULTS: Diagnosis was made on histologic data in 38.7% and 41.8% of the hospital based and population-based studies, respectively, with a wide variation among different hospitals. The percentage of cases classified as PLC was 78.6% in the hospital based study and 78.8% in the population-based study. No differences in the proportion of cases attributed to PLC were found according to patients' age and sex or hospital of admission. The repeatibility of the procedure was assessed by a cross-panel review of 198 cases, and concordance was found in 91.9% of them. CONCLUSIONS: An operational method for case definition of PLC based on the results of the diagnostic examinations currently performed and some suggestions for cancer registration are proposed. PMID- 7778222 TI - Second-generation aromatase inhibitors. PMID- 7778223 TI - Prostate cancer: population-based survival rates in central Italy. AB - AIMS: To evaluate survival in prostate cancer patients in the Province of Florence where the Tuscany Cancer Registry is active. METHODS: The survival of 777 patients with prostate cancer diagnosed in the period 1985-87 was evaluated. The observed and relative survival rates 1, 3 and 5 years after diagnosis were computed. Also the prognostic effect of age, disease extension, tumor grade, histological verification, place of residence and year of diagnosis were evaluated using univariate and multivariate analysis. RESULTS: The observed survival was 73.4% 1 year, 42.5% 3 years and 29.2% 5 years after diagnosis. The relative survival was respectively 78.7%, 53.0% and 43.0%. Significant independent risks were evident when the disease was extended out of the prostate, for patients older than 80 years, for high grade tumors and for patients without histological verification. CONCLUSION: The 5-year relative survival rate in the province of Florence is similar to those from other European Registries and the Latina Registry, but much lower than the one reported by the SEER program in the US. Data on histological verification percentage, availability of information on disease extension, and tumor grade are discussed as indicators of the quality of the diagnostic approach in comparison with other registries. PMID- 7778226 TI - [Laparoscopic surgery of the digestive system: present and future]. PMID- 7778225 TI - Feasibility of intraportal chemotherapy with fluorouracil and folinic acid immediately after hepatic resection for colorectal metastases. AB - BACKGROUND: About 50% of recurrence after resection of hepatic metastases from colorectal cancer remain confined to the liver. Adjuvant locoregional treatments could reduce the failure rate, but these treatments have been scantily investigated. Experimental models have shown that both intra-arterial chemotherapy (IAC) and intraportal chemotherapy (IPC) in adjuvant setting were able to reduce metastatic growth, but IPC should be initiated in the immediate postoperative period. AIMS: To evaluate the feasibility of immediate postoperative IPC of fluorouracil (5-FU) plus folinic acid (FA) in a consecutive series of patients undergoing hepatic resection for metastatic colorectal cancer. METHODS: Forty-three consecutive patients underwent hepatic resection. The first 25 (Control Group = CG) received only surgery; the latter 18 (Treated Group = TG) were candidate to postoperative IPC of 5-FU 750 mg/m2 plus FA 20 mg/m2/day continuous infusion for 8 days. One patient was not treated owing to bleeding, thus only 17 received the treatment. RESULTS: Postoperative morbidity was 14%, equally distributed in both groups. Biochemical hepatic parameters of TG were not statistically different from those of CG. Five patients (29%) developed systemic toxicity: one hematologic grade 4; 3 mucositis grade 3 and one allergic erythema. Three of these patients had been treated by systemic chemotherapy less than one year before. DISCUSSION: IPC of 5-FU plus FA in the immediate postoperative period has not yet been tested. The schedule we have investigated neither affected the postoperative outcome, nor influenced hepatic function and regeneration. Systemic toxicity was evident and severe mainly in patients already pretreated by systemic chemotherapy. In these patients, however, toxicity did not affect further outcome. This study confirms the feasibility of immediate intraportal chemotherapy after hepatic resection. PMID- 7778228 TI - [Surgical treatment of poliomyelitis sequelae in the legs. 118 cases in Togo]. PMID- 7778227 TI - [Allergic rhinitis]. PMID- 7778229 TI - [Blunt kidney traumas. 51 cases]. PMID- 7778230 TI - [Evaluation in neonates of infectious risk during premature rupture of membranes. (Prospective study of 100 cases)]. PMID- 7778231 TI - [Contraception and unwanted pregnancies. 139 cases]. PMID- 7778232 TI - [Treatment of divergent intermittent strabismus]. PMID- 7778233 TI - [A rare cause of liver abscess]. PMID- 7778234 TI - [Management of undesirable side effects of medications]. PMID- 7778236 TI - [Alternative physical treatment--a real offer?]. PMID- 7778235 TI - [New medical treatments in Great Britain]. PMID- 7778237 TI - [Alternative treatment of athletic injuries]. AB - A questionnaire was carried out in a Danish sports clinic to find out how many sports-injured patients seek alternative medical treatment. One hundred and fifty persons (81%) answered the questionnaire. Forty-seven percent of the women and 35% of the men had at some time tried alternative medicine. These high numbers might be explained by dissatisfaction with the official medical treatment of sports injuries in Denmark. No age or income difference was found between the persons who had tried alternative medicine compared to the patients who had never tried it. Fifty-nine percent of those who had sought alternative medicine did not find it effective. There is a need for clinically controlled trials to find out if some alternative medical treatments do have effects on some specified injuries. PMID- 7778238 TI - [Intracoronary ultrasonography--a supplement to coronary arteriography]. AB - Intracoronary ultrasound is a new technique, by means of which it is possible for the first time to visualise coronary artery wall structures in vivo. Compared to conventional coronary angiography the advances of this new modality appear to be: 1) Improved diagnosis of minimal and non-obstructive atherosclerosis; 2) Characterisation of plaque morphology, thereby being an aid in decision on interventional procedures (PTCA, atherectomy, stent placement); 3) Better delineation of coronary artery lumen area, which improves the accuracy of stenosis graduation both before and after interventional procedures. The examination can be performed in up to 95% of cases. The procedure appears to be safe with a reported complication rate of myocardial infarction and bypass surgery of 0.16% in 1837 cases; transient coronary artery spasms occurred in about 3%. Complications are predominantly associated with interventional procedures. Although intracoronary ultrasound has mainly been used for research purposes, results of ongoing trials assessing its clinical utility, as well as technological improvement providing more consistent image quality, suggest that the procedure will evolve into an important adjunct to coronary angiography. PMID- 7778239 TI - [Non-invasive transcranial brain stimulation in man]. AB - Magnetic stimulation of the brain in awake human subjects was introduced ten years ago and has since then been used extensively both in the clinic and for research purposes. So far the method has been shown to be of importance as a supplement to other methods in the diagnosis and monitoring of multiple sclerosis. It may also achieve importance as a prognostic tool in early cerebral haemorrhage. It is yet unclear whether the method will achieve any importance in the diagnosis of other diseases such as Parkinsons disease, migraine and epilepsy. The method has caused a major breakthrough in the investigation of the central control of voluntary movement in man. The method thus provides a possibility of monitoring the activity of defined corticospinal pathways during voluntary movements. PMID- 7778240 TI - [Prognosis for patients admitted to intensive care units with acute renal failure requiring dialysis]. AB - The mortality of critically ill patients who develop acute renal failure (ARF) is persistingly high. We reviewed all patients who developed ARF that required dialysis in a single intensive care unit (n = 167) during the period 1977 to 1989, in order to identify variables with possible influence on outcome. Overall mortality within hospital was 75%. Age above 60 (p < 0.02), requirement for mechanical ventilation (p < 0.0005), requirement for inotropic drugs (p < 0.0005) and increased levels of P-bilirubin (p < 0.005) had negative impacts on survival. Mortality increased significantly from 63% in the early period (1977-1985) to 84% in the late period (1986-1989) (p < 0.001), a rise that could not be explained by a single variable. The patients in the later period were, though, characterized by a higher morbidity with a higher frequency of additional organ failure. PMID- 7778241 TI - [Optimization of radiotherapy of cervical cancer. Introduction of an extern radiotherapy based on CT and low-dosage afterload technique at the Rikshospitalet]. AB - In September, 1987 remote controlled afterloaded caesium in treatment of carcinoma was introduced at the Department of Oncology, Copenhagen University Hospital. All patient data, treatment, complications and deaths were registered prospectively. This study describes treatment results of the first 178 consecutively treated patients. The four year survival rates for patients stage I, II and III were 70%, 68% and 43%, respectively. The stage I patients were all considered unfit for surgery due to age or other medical conditions. During the observation period 13 patients developed severe complications requiring surgery, and three of these patients died. It was concluded that treatment with afterloaded caesium for carcinoma of the cervix has reduced radiation of the medical personnel to an almost unmeasurable dose, that the treatment results were comparable to those of the larger centres in the world and that the new treatment technique suggests further improvement in the treatment of cervical carcinoma. PMID- 7778242 TI - [Upper dyspepsia in persons aged 50 to 60 years. Results from a 5-year follow-up population study in Glostrup]. AB - A five year follow-up study of a large random cohort was carried out with the aim of finding prevalence, incidence, prognosis and risk factors for upper dyspepsia according to different definitions. Fifty-four percent of the men and 47% of the women had experienced symptoms of upper dyspepsia within the past 12 months, while the prevalence of frequently occurring symptoms was 13% among men and 15% among women. Similarly the incidence was 22% among men and 25% among women, declining to 5% and 6% respectively when only frequent symptoms were considered. At five years follow-up approximately one quarter of the subjects with upper dyspepsia had recovered from all symptoms, while two thirds of the subjects who had experienced frequent symptoms did not do so any more. Psychological vulnerability increased the risk of having upper dyspepsia by 3.8, and risk of developing upper dyspepsia within five years 2.3. Different definitions identified different subjects as suffering from upper dyspepsia, and less than one quarter of the subjects fitted all the definitions. PMID- 7778243 TI - [Quality assurance of scintigraphic examinations of cerebral circulation. Presentation of a method]. PMID- 7778244 TI - [Femoral pseudoaneurysms in drug addicts]. AB - Four cases of femoral pseudoaneurysms from substance abuse are presented. One patient, a 32 year-old women needed amputation (by disarticulation of the hip) after failed revascularization. Another patient had symptoms of claudication after triple ligation and resection without bypass grafting. The last two had an uneventful recovery: one after saphenous vein bypass, the other after simple resection and repair with a vein patch. PMID- 7778245 TI - [Breast cancer]. PMID- 7778246 TI - [Endoscopy for treatment with H2 blockaders?]. PMID- 7778247 TI - [Infertility]. PMID- 7778248 TI - Vascular supply of the tendon of the equine deep digital flexor muscle within the digital sheath. AB - The vascular and microvascular anatomy of the equine deep digital flexor tendon (DDFT) within the digital sheath was studied by injecting the vasculature with either colored latex or barium sulphate for radiographic, microangiographic, histologic, and computed tomographic (CT) evaluation. Consecutive 4-mm thick two dimensional CT slice data were reconstructed to 3-dimensional volumetric images to enhance spatial evaluation of the blood supply. Gross dissection and angiographic studies identified three major vascular sources. Above the fetlock, the DDFT was supplied by either a branch of the medial palmar artery (Arteriae digitalis palmaris communis II) or a branch of the medial palmar digital artery (A. digitalis [palmaris propria III] medialis). Below the fetlock, the DDFT was supplied by branches from the lateral and medial palmar branches to the proximal phalanx (Ramus palmaris phalangis proximalis). The most distal aspect of the tendon received small branches from the medial and lateral palmar digital arteries. Using histology and microangigraphy we observed an extensive and uniform intratendinous vascular network above and below the fetlock, with a relatively avascular region of tendon palmar to the fetlock. The most distal 2.0 to 2.5 cm of the tendon within the sheath was heavily infiltrated with fibrocartilage along its dorsal aspect. PMID- 7778250 TI - An evaluation of fiberglass cast application techniques. AB - Cylindrical casts constructed from 2, 3, 4, and 5 inch widths of fiberglass casting material were evaluated for strength in bending using an unstable fracture model. Five-inch casting material produced the strongest casts. The effect of longitudinal splinting with 2-inch fiberglass tape was evaluated in cylindrical casts constructed from 4-inch tape. Casts with splints on the compression side or with splints on both the tension and compression sides were stronger in bending than casts with a single splint on the tension side or casts without splints. PMID- 7778249 TI - Intraperitoneal use of sodium carboxymethylcellulose in horses undergoing exploratory celiotomy. AB - The effect of intraperitoneal sodium carboxymethylcellulose (SCMC) administration on clinical outcome and survival was evaluated in horses undergoing exploratory celiotomy for acute gastrointestinal disease. Comparison of variables was made retrospectively between 44 horses that had SCMC and 92 horses (controls) not treated with SCMC. Mean age, body weight, heart rate, packed cell volume and plasma total protein of horses at admission, and convalescent period were not significantly different between control and SCMC groups. No significant differences were noted between control horses and SCMC horses with respect to incisional infection, hernia formation, recurrent episodes of colic, clinical outcome, and long-term survival (> 6 months). Seventy-six (83%) control horses and 34 (77%) SCMC horses survived long-term. Seventy (76%) control horses and 30 (68%) SCMC horses survived without complications and returned to their previous use. These results suggest that intraperitoneal use of SCMC does not adversely affect abdominal incisional wound healing, clinical outcome or long-term survival, however, the efficacy of SCMC in prevention of postoperative intestinal adhesions in horses requires further investigation. PMID- 7778251 TI - Clinical effects of longitudinal division of the corpus callosum in normal dogs. AB - Longitudinal division of the corpus callosum was performed in six normal beagles to determine surgical morbidity. The corpus callosum was divided sagittally on the midline and the effect on neurological function was determined. Five of six dogs were clinically normal within 14 days or less after surgery. One dog had persistent but improving clinical signs consistent with a forebrain disturbance at 30 days after surgery. Overall, minimal morbidity and no mortality was associated with this surgical procedure. Further study is indicated to determine the efficacy of this surgical treatment for seizure control in dogs with idiopathic epilepsy. PMID- 7778252 TI - Clinicopathologic effects of a 21-aminosteroid compound (U74389G) and high-dose methylprednisolone on spinal cord function after simulated spinal cord trauma. AB - A model simulating acute-compressive spinal cord trauma at the second lumbar spinal cord segment (100 g, 300 seconds) was used to evaluate the efficacy of a vehicle control, methylprednisolone sodium succinate (MPSS), and a 21 aminosteroid compound (U74389G). Dogs were allocated into one of five treatment groups (A to E) using ultrasonographic determination of spinal cord diameters to ensure even distribution of spinal cord diameters among the treatment groups. Initial dosages of the vehicle control (A), methylprednisolone (30 mg/kg of body weight) (B), or U74389G (30 mg/kg, 3 mg/kg, or 10 mg/kg of body weight) (C, D, or E, respectively) were administered intravenously 30 minutes after trauma. Dosages were reduced by one-half for 2 and 6 hour treatments. Then every 4 hours for 42 hours, dosages were reduced one-third and one-sixth from the original dose of methylprednisolone and U74389G, respectively. Neurological examinations were performed daily for 21 days. Histopathological examination of the traumatized spinal cord showed malacic and degenerative lesions. Although significant differences in some portions of the neurological and histopathologic examinations were observed, clinical efficacy for MPSS and U74389G could not be established in this model. PMID- 7778253 TI - Treatment of perianal fistulas with ND:YAG laser--results in twenty cases. AB - Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs. PMID- 7778254 TI - The intercondylar fossa of the normal canine stifle an anatomic and radiographic study. AB - The intercondylar fossa (ICF) in dogs consists of a cranial outlet, intercondylar shelf, caudal arch, caudal outlet, a medial wall, and a lateral wall. The normal cranial outlet is bell-shape and, in mixed-breed dogs (mean body weight 19.2 kg, N = 21), measured 5.8 mm cranially, 8.1 mm centrally, and 10.3 mm caudally. The ICF is oriented 12 degrees from the dorsal plane of the femoral diaphysis and obliqued 7 degrees, proximolateral to distomedial, in the sagittal plane. To adjust for dog size, a fossa width index (FWI) was calculated by dividing the cranial outlet width by the distance between epicondyles. The normal FWI as determined in this study was 0.18 cranially, 0.25 centrally, and 0.32 caudally. The fossa height index 0.31. Contact between the ICF and the cranial cruciate ligament began at about 115 degrees of extension. The contact area moved cranially in the intercondylar fossa as the stifle was extended. Evaluation of the ICF can be performed radiographically but positioning is critical. PMID- 7778256 TI - Ovariohysterectomy in six mares. AB - Six mares had ovariohysterectomy performed for chronic pyometra associated with cervical abnormalities, uterine neoplasia, or removal of a macerated fetus. Ovariohysterectomy was performed through a ventral midline incision with access to the ovarian and uterine vessels aided by traction on the uterus and retraction of abdominal viscera. Abdominal pain, the most common complication after surgery, occurred in four mares but resolved within 36 hours. Peritonitis occurred in two mares; one mare was subsequently euthanatized. Other complications that resolved with treatment included infection of the uterine stump (two mares), abdominal hemorrhage (one mare), diarrhea (one mare), and incisional infection (one mare). Complications after surgery can be reduced by removing as much of the uterus as possible, minimizing peritoneal contamination with uterine contents, and providing a secure closure of the caudal reproductive tract. PMID- 7778255 TI - The effect of intercondylar notchplasty on the normal canine stifle. AB - This study evaluated the effect of notchplasty (enlargement of the intercondylar fossa) in stable and unstable canine stifles. Bilateral notchplasty and unilateral cranial cruciate ligament (CrCL) transection were performed in 6 dogs. Exercise, consisting of walking 1.5 miles three times a week, began 1 month after surgery and continued until euthanasia 6 months after surgery. Evaluation methods included orthopedic examination, serial radiographs, thin section radiography, histopathology, and gross pathology. Notchplasty in the stable stifle did not cause lameness beyond 3 weeks, joint instability, or degenerative joint disease. In the stable stifle, smooth resurfacing of the notchplasty site with fibrous and osseous tissue occurred. Stifles with notchplasty and CrCL transection exhibited persistent lameness, instability, and degenerative joint disease. In CrCL deficient stifles osteophytes formed within the notchplasty site, resulting in a rough surface. Our observations indicated significant refilling in notchplasties of both stable and unstable stifles (P < .05). However, the intercondylar fossa (ICF) width 6 months after notchplasty was significantly smaller in unstable stifles compared with stable stifles (P < .05) indicating that greater refilling of the notchplasties occurred in the unstable stifles. In clinical cases, notchplasty should be larger than the desired final result to accomodate the partial refilling that occurs even in stable stifles. PMID- 7778257 TI - Skin fold advancement flaps for closing large sternal and inguinal wounds in cats and dogs. AB - Skin fold advancement flaps can be created from the elbow and flank folds to close large wounds in the pectoral and inguinal regions of cats and dogs, respectively. The attachments of the laterally facing (outer) and medially facing (inner) layers of the skin fold to the adjacent limb are divided to produce a U shaped pedicle graft attached to the trunk. This mobilizes skin that can be advanced over large wounds involving the ventral chest or abdomen, or both. The use of skin fold advancement flaps enables direct closure of large skin defects without undue tension and without compromising the mobility of the adjacent limb. PMID- 7778258 TI - Demineralized bone matrix (DBM) PMID- 7778259 TI - Incomplete ossification of the humeral condyle in spaniels. PMID- 7778260 TI - Evaluation of the hemodynamic effects of interpleural bupivacaine in dogs. AB - The hemodynamic effects of interpleural (IP) bupivacaine were studied in six halothane-anesthetized dogs. On four separate occasions, each dog received IP saline (S), or bupivacaine at a low dosage of 1.5 mg/kg (L), high dosage of 3.0 mg/kg (H), or high dosage of 3.0 mg/kg with epinephrine 5 micrograms/mL (HE). Heart rate, systolic and mean arterial pressures, and base excess were significantly lower in the H dosage group than in the other treatment groups. Cardiac output, expressed as a percentage of change from baseline, was significantly higher in the L group than in the H and S groups. Pulmonary arterial pressure and respiratory rate were significantly higher in the HE group than in the other three groups. Mean plasma concentrations of bupivacaine peaked between 5 and 15 minutes after IP injection. Maximum plasma concentrations in individual dogs were variable; however, mean maximum plasma concentrations in the H and HE groups were not significantly different. Clinically significant hypotension occurred in one dog in the H group and in one dog in the HE group. No pulmonary complications were detected. PMID- 7778261 TI - Evaluation of propofol as a general anesthetic for horses. AB - This study provides baseline information on the potential use of propofol as a general anesthetic for horses. Using a Latin square design, propofol (2, 4, and 8 mg/kg) was administered intravenously on three separate occasions to six mature horses. Information about anesthetic induction, duration, and recovery was recorded along with results of rectal temperature, heart rate, respiratory rate, pHa, PaCO2 and PaO2. Statistical analysis included a mixed model analysis of variance, a general linear model analysis and least square means test for post hoc comparisons. A P < .05 was considered significant. The quality of induction of anesthesia varied from poor to good. Two horses were not recumbent following the lowest dose of propofol. Brief paddling limb movements occurred occasionally and unpredictably after recumbency induced by all three doses. During recovery, horses were uniformly calm and coordinated in their moves to stand. Duration of recumbency (minutes) was dose related; 15.05 +/- 1.58 (mean +/- SD) following 2 mg/kg, 31.06 +/- 5.56 following 4 mg/kg, and 47.85 +/- 13.63 following 8 mg/kg. During recumbency at all doses, heart rate significantly increased from a predrug value of 40 +/- 6 beats per minute. Substantial respiratory depression, characterized by a significant decrease in respiratory rate (from 11.7 +/- 2.9 to 3.7 +/- 1.6 breaths per minute) and increased PaCO2 (from 44.5 +/- 2.5 to 52.7 +/ 8.0 mm Hg) was seen only after 8 mg/kg. A significant decrease in PaO2 was observed throughout the recumbency induced by 8 mg/kg, and also at 3 and 5 minutes following induction of anesthesia with 4 mg/kg propofol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778262 TI - Alterations of endothelium-dependent digital vascular responses in horses given low-dose endotoxin. AB - Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 microgram/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Cumulative concentration response curves to acetylcholine, bradykinin, nitroprusside, norepinephrine, 5-hydroxytryptamine (serotonin), and endothelin were determined. Maximal relaxation or contraction and the concentrations needed to produce 50% maximal relaxation or contraction were determined. Palmar digital arteries from endotoxin-treated horses relaxed significantly less in response to acetylcholine and bradykinin (endothelium-dependent), but not to nitroprusside (endothelium independent) when compared with arteries from control horses. Digital arteries from endotoxin-treated horses also contracted significantly more with norepinephrine but less with serotonin. Digital veins responded less than digital arteries. In another study, vascular reactivity experiments documented that acetylcholine and bradykinin were endothelium-dependent vasodilators (endothelium denuded vessels relaxed less than control vessels) in palmar digital vessels. Additionally, maximal relaxations for both vasodilators were significantly inhibited by N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist, suggesting that acetylcholine and bradykinin cause relaxation through the nitric oxide pathway. The data from these studies indicate that low dose endotoxin impairs endothelium-dependent relaxation and augments adrenergic contraction of palmar digital arteries in horses. PMID- 7778263 TI - Development of a colic severity score for predicting the outcome of equine colic. AB - Thirty-two physical examination and laboratory variables were recorded during examination of 165 horses admitted for acute abdominal disease. Univariate analyses were performed to determine which of the variables were significantly different between horses that lived or died. Stepwise logistic regression was performed to identify variables with the best predictive value. Four variables (heart rate, peritoneal fluid total protein concentration, blood lactate concentration, and abnormal mucous membrane) remained significant when entered into the model. Histograms for each significant variable were used to set "cutting-points," establishing categories that were made into a table of assigned values from which a Colic Severity Score (CSS) for each horse was calculated. Seventy-one horses in a second group were used to validate the scoring chart. Case mortality rate was similar in both groups (20.6% in development group versus 21.1% in validation group). All horses with a CSS > 7 died, whereas 75% of those with a score of < or = 7 lived. For the validation group, use of the scoring table yielded a positive predictive value of 100%, negative predictive value of 91.8%, sensitivity of 66.7%, and specificity of 100%. The overall accuracy of the CSS was 93%. The CSS is a rapid and accurate method for predicting survival in cases of equine acute abdominal disease. PMID- 7778266 TI - Intragenomic complementation of a 3AB mutant in dicistronic polioviruses. AB - We report the construction of a poliovirus genome [pPVM-VPg(3F4A)] harboring a double mutation in VPg. This mutant, in which the tyrosine and the threonine at residues 3 and 4 of the VPg region were replaced by phenylalanine and alanine, respectively, is lethal, that is, all RNA synthesis was abolished and no revertants could be isolated. Using the properties of dicistronic polioviruses (with the general genotype PV 5'NTR-3AB-EMCV IRES-PV ORF-3'NTR), we have observed that the defect in RNA synthesis of the VPg(3F4A) mutant could be rescued by providing wild-type protein 3AB from the first open reading frame in trans. We conclude that the 3AB provided by the first cistron of the dicistronic construct was capable of "intragenomic complementation." Intragenomic complementation, however, was inefficient. Thus, the dicistronic RNAs were only quasi-infectious, and even first-passage viruses were found to have reverted to a functioning VPg in the polyprotein. This phenomenon underlines the role of polypeptide 3AB in multiple functions of viral proliferation. First-passage viruses, all of which expressed a small-plaque phenotype, had retained the original dicistronic genotype. At the fourth passage, however, all isolates were monocistronic, and they displayed complex genetic rearrangements revealing interesting information regarding IRES function. PMID- 7778265 TI - Generation of thymidine kinase-deficient mutants of infectious laryngotracheitis virus. AB - Current vaccines for the avian respiratory disease infectious laryngotrachetitis consist of naturally attenuated strains of the causative agent--the herpesvirus infectious laryngotracheitis virus (ILTV). Due to the dissemination of these viruses from vaccinated chickens as well as their possible reversion to more pathogenic forms, the use of genetically engineered viral vaccines lacking virulence factors while retaining antigenicity is being considered. Since the thymidine kinase (TK) activity of herpesviruses has been associated with virulence, inactivation of the encoding gene in the ILTV genome should attenuate the virus. Moreover, by analogy to other TK- herpesviruses, the ability of such ILTV mutants to induce a protective response in chickens should not be compromised. Therefore, the deliberate genetic alteration of ILTV was attempted. In order to prevent reversion and also to enable identification of the modified virus, a "marker" transcriptional unit (Escherichia coli lacZ gene fused to a SV 40 3'-polyadenylation signal sequence and regulated by the pseudorabies virus gX gene promoter) was inserted via homologous recombination at one of two loci within the ILTV TK gene. Recombinant viruses were identified and plaque-purified on the basis of their ability to produce beta-galactosidase. Retention of the foreign DNA at the predicted sites in the genomes of the recombinant ILTV was verified by Southern hybridization. Since their replication was unaffected by the thymine analog 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-methyluracil, the recombinants appeared to have a TK- phenotype. Despite this apparent deficiency, prior inoculation of either recombinant virus into chickens afforded the birds protection against a lethal challenge of virulent ILTV. Moreover, the degree of respiratory distress in the chickens vaccinated with the recombinants was relatively mild compared to the severe reaction in birds receiving the parental virus. Thus, ILTV can be genetically attenuated without an accompanying loss of immunogenicity. PMID- 7778264 TI - Erratic G-->A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus. AB - The complete nucleotide sequence of an integrated provirus of caprine arthritis encephalitis virus (CAEV) has been determined. The provirus was defective due to extensive G-->A hypermutation. Rather than being a smooth phenomenon distributed throughout the genome it was highly erratic with hypermutated and normal regions being juxtaposed, probably reflecting local fluctuations in the intracellular dCTP pool during reverse transcription of the CAEV genome. The pattern of sequence variation within the surface glycoproteins differs subtly from that of the primate lentiviruses. PMID- 7778267 TI - Isolation of high-affinity RNA ligands to HIV-1 integrase from a random pool. AB - We were able to isolate high-affinity RNAs from a random pool that binds to integrase protein from the human immunodeficiency virus-type 1 using the procedure now known as SELEX. Generally, the RNAs fell into three different classes in binding buffer containing 250 mM NaCl: group I class of molecules binds integrase with a dissociation constant (Kd) on the order of 10 nM, group II molecules had a Kd of about 80 nM, and group III about 800 nM. The RNA with the highest affinity from the group I class of molecules, designated P5, was characterized using computer modeling, chemical and enzymatic probing, and deletion analysis. Our secondary structure model for this RNA suggests interactions between looped-out fixed nucleotides and nucleotides from the randomized region; a GNRA tetraloop is also in the structure. We showed that our integrase was able to process a U5 mimic in vitro. P5 competes effectively for binding with the double-stranded DNA mimic of U5 at 180 mM NaCl concentration. PMID- 7778268 TI - Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA. AB - Coronavirus infection of mice has been used extensively as a model for the study of acute encephalitis and chronic demyelination. To examine the evolution of coronavirus RNA during chronic demyelinating infection, we isolated RNA from intracerebrally inoculated mice at 4, 6, 8, 13, 20, and 42 days postinfection and used reverse transcription-polymerase chain reaction amplification methods (RT PCR) to detect viral sequences. RNA sequences from two viral structural genes, the spike gene and the nucleocapsid gene, were detected throughout the chronic infection. In contrast, infectious virus was not detectable from brain homongenates beyond 13 days postinfection. These results indicate that coronavirus RNA persists in the brain at times when infectious virus is not detected. To determine if genetic changes were occurring during viral replication in the host, we cloned and sequenced the RT-PCR products from the spike and nucleocapsid regions and analyzed the sequences for mutations. Sequencing of the cloned products revealed that a variety of mutant forms of viral RNA persisted in the CNS, including point mutants, deletion mutants, and termination mutants. The mutations accumulated during persistent infection in both the spike and the nucleocapsid sequences, with greater than 65% of the mutations encoding amino acid changes. These results show that a diverse population or quasispecies consisting of mutant and deletion variant viral RNAs (which may not be capable of producing infectious virus particles) persists in the central nervous system of mice during chronic demyelinating infection. The implications of these results for the role of persistent viral genetic information in the pathogenesis of chronic demyelination are discussed. PMID- 7778269 TI - Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins. AB - Transcriptional activation of HIV-1 gene expression by the viral Tat protein requires the interaction of a cellular cofactor with the Tat activation domain. This domain has been shown to consist of the cysteine-rich and core motifs of HIV 1 Tat and is functionally conserved in the distantly related Tat proteins of HIV 2 and EIAV. Using the yeast two-hybrid system, we have identified a novel human gene product, termed HT2A, that specifically and precisely binds to the activation domain of HIV-1 Tat and that can also interact with the HIV-2 and EIAV Tat proteins in vivo. We present data further demonstrating that the interaction between the activation domain of HIV-1 Tat and the HT2A protein can be readily detected in the mammalian cell nucleus. Sequence analysis demonstrates that HT2A is a novel member of the C3HC4 or ring finger family of zinc finger proteins that includes several known oncogenes and transcription factors. Overall, these data suggest that HT2A may play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. PMID- 7778270 TI - Altered dinucleotide content within the latently transcribed regions of the DNA of alpha herpes viruses--implications for latent RNA expression and DNA structure. AB - The alphaherpesviruses establish latent infections in sensory neuronal cells, during which a number of latency-associated RNA transcripts (LATs) are produced. The reasons for the production of the LATs, however, and the mechanism by which the LAT region of the genome remains active during latency are unknown. Here we have analysed alphaherpesvirus sequences in an attempt to assess any differences between latently active regions of the genomes and the genomes as a whole which might be necessary for this differential expression pattern or for the LAT function, whatever that might be. We show that the LAT regions of all of the four alphaerpesviruses examined exhibit a previously unidentified and marked increase in CC + GG dinucleotides within the region and that three of the four viruses examined also show a marked decrease in CG + GC dinucleotides. The CC + GG increase was shown to occur throughout the LAT regions of these viruses, but the GC + CG decrease was shown to be confined only to LATs which are thought to be expressed as introns, and also to the intron sequences of the IE1 genes (at least for herpes simplex viruses 1 and 2), which overlap the LAT region. Bovine herpesvirus, the virus which did not show the GC + CG reduction in its LAT region but did show the GG + CC increase, is thought not to express LATs by a mechanism involving splicing, again indicating that the CG + GC reduction may be an intron related phenomenon and also further suggesting that the two effects of CG + GC decrease and GG + CC increase may be independent of one another. Possible reasons for these unusual dinucleotide frequencies within the latently active regions of the alphaherpesviruses relating to DNA and RNA structure and to LAT function are discussed. PMID- 7778271 TI - Genetic stability and mutant selection in Sabin 2 strain of oral poliovirus vaccine grown under different cell culture conditions. AB - Mutations that consistently accumulated in the attenuated Sabin 2 strain of poliovirus during propagation in cell cultures were identified by sequence heterogeneity assay and quantified by mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Eight additional sites previously identified in stool isolates were also examined by MAPREC in the virus passages. The pattern of selectable mutations and the rate of their accumulation depended on the type and confluence of the cell culture and the temperature of virus growth. Five unstable genomic sites were identified in Sabin 2 virus passaged 10 times at 34 degrees in African green monkey kidney (AGMK) cells, with the mutations accumulating in the range 1 to 24%. Accumulation of these mutations did not appear to result in a loss of attenuated phenotype since the virus passaged under these conditions passed the monkey neurovirulence test (MNVT). The content of the 481-G revertant known to be related to neurovirulence in monkeys did not increase. Thus, our results suggest that upon growth of Sabin 2 virus in AGMK cells at 34 degrees, the key determinant(s) of attenuation remained stable, and the mutations that occurred did not affect monkey neurovirulence. In virus passaged 10 times at 37 degrees in AGMK cells, 4 unstable genomic sites were identified, in some of them accumulating up to 12% of the mutants. This virus sample severely failed the MNVT. Virus passaged in Vero cells at 34 and 37 degrees accumulated mutants at 7 and 14 genomic sites, respectively, including 481-G in both cases, with almost complete substitution of the original nucleotides at some of the sites. We tested 44 commercial monopools of Type 2 OPV and found out that all of them contained 481-G revertants in the range 0.4-1.1%. An increase in the 481-G revertants in passaged viruses to the level of 4% and above correlated with failure of these samples by the MNVT. Since the pattern of selectable mutations differed in viruses grown in the two cell cultures used in this study, specific mutation profiles should be determined for each cell substrate used for vaccine production to assess manufacturing consistency. PMID- 7778273 TI - Developmental resistance in fourth instar Trichoplusia ni orally inoculated with Autographa californica M nuclear polyhedrosis virus. AB - Larvae of lepidopteran insects commonly become increasingly resistant to baculovirus infections as they age. The mechanism responsible for this development resistance is not known, but the phenomenon does not occur if the viral inoculum is administered intrahemocoelically instead of orally, which is the natural route of infection. This observation indicates that the factors mediating developmental resistance are operative during infection of the primary target tissue, the larval midgut, and not during subsequent systemic infection. To learn more about the mechanism of developmental resistance, we orally inoculated four cohorts of fourth instar Trichoplusia ni larvae with a recombinant of Autographa californica M nuclear polyhedrosis virus expressing a reporter gene. While these cohorts differed only by a few hours in age, we found increasing resistance to infection in successively older cohorts. By assessing the presence and location of infected cells at intervals during the first 48 hr after inoculation, we identified two key factors relevant to the resistance pattern among the developmental cohorts. These factors were: (i) an age-dependent rate of establishing and/or sloughing infected midgut cells and (ii) the ability of fourth instar T. ni to completely clear infection of the midgut epithelium by ecdysis to the fifth instar. PMID- 7778272 TI - Transmissible retrovirus in Epstein-Barr virus-producer B95-8 cells. AB - Epstein-Barr virus (EBV) released from the B95-8 marmoset cell line has served as a prototype for biologic and biochemical studies of EBV. Here we identify and characterize a retrovirus carried by many cultures of B95-8 cells. The experiments were stimulated by the isolation of a cDNA clone from B95-8 cells in which sequences from the EBV large internal repeat were linked to gag sequences similar to those of squirrel monkey retrovirus, human isolate, SMRV-H. However, among 413 amino acids predicted from the nucleotide sequence of the gag region of the B95-8 SMRV isolate there were 48 amino acid changes that distinguished this virus from SMRV-H originally isolated from a human lymphoid cell line by Oda et al. (1988, Virology 167, 468-476). Nucleic acid and antibody probes were developed for the B95-8 isolate of SMRV. Using such probes, we found that SMRV B95-8 was readily transmissible, independent of EBV, as an infectious virus to human B and T cell lines. SMRV-B95-8 was highly fusogenic in the presence or absence of EBV. The ultrastructural appearance of the B95-8 retrovirus was characteristic of a type D retrovirus. Cells dually infected with EBV and SMRV B95-8 did not demonstrate increased levels of lytic EB viral replication. SMRV B95-8 did not by itself cause lymphocyte immortalization or enhance immortalization by EBV. Thus SMRV-B95-8 does not contribute to the major biologic properties of the B95-8 strain of EBV. PMID- 7778274 TI - Feline immunodeficiency virus (FIV)-specific cytotoxic T lymphocytes from chronically infected cats are induced in vitro by retroviral vector-transduced feline T cells expressing the FIV capsid protein. AB - We have previously reported the presence of feline immunodeficiency virus (FIV) specific, major histocompatibility complex (MHC)-restricted cytolytic T lymphocytes (CTL) in experimentally FIV-infected cats. However, the fine specificity of the CTL and the role of individual FIV proteins in inducing FIV specific CTL responses remain unknown. In this study, we examined the in vitro induction and activity of FIV p24 capsid-specific CTL obtained from cats that had been experimentally infected with FIV Petaluma for 30 to 56 months. An amphotropic murine retroviral vector was used to generate transgenic primary feline T lymphoblasts that expressed the FIV capsid protein. When the autologous capsid-transduced T cells were used in vitro to stimulate CTL responses from peripheral blood mononuclear cells of chronically infected cats, MHC-restricted lysis of virus-infected target cells was observed. The majority of the CTL expressed CD8, and depletion of this population, but not CD4+ cells, effectively diminished the CTL activity. When the autologous capsid-transduced T cells were used as target cells, lysis by capsid-induced effectors was not observed. Analysis of capsid-transduced T cell clones revealed a variable and low level of capsid expression among the clones. This study demonstrates the potential for using retroviral vectors as a means of inducing CTL effector cells that will specifically kill lentivirus-infected cells during lentiviral infection. PMID- 7778275 TI - Sequence of ovine adenovirus homologs for 100K hexon assembly, 33K, pVIII, and fiber genes: early region E3 is not in the expected location. AB - Ovine adenovirus OAV287 was previously isolated from sheep in Western Australia. As a first step in characterizing the genome of this virus we have determined the sequence of its genome between map units 65 and 81. This region was expected to contain the nonessential E3 region which, in other adenoviruses, lies between the genes encoding the pVIII and fiber proteins, although its size and complexity varies. OAV287 genes coding for the hexon assembly, 33K, pVIII, and fiber proteins were identified by their homologies with human Ad2. These genes lie in the same relative positions in the OAV287 genome, but the intergenic region between the pVIII and the fiber genes is only 197 nucleotides and these appear to be incapable of coding for any protein. Thus, the ovine adenovirus E3 region is not present in the expected location. In addition, using cDNA synthesis, PCR amplification, and nucleotide sequencing we determined the location of splice junctions and transcription termination signals in mRNA species encoding these proteins. This showed that a family of variably spliced L4 RNAs is produced and that the region between the pVIII and the fiber genes contains several signals for RNA synthesis and processing. As the E3 region in human adenoviruses is nonessential for replication, in many instances it has been replaced with foreign DNA during the construction of recombinants. Because of this unexpected difference in the organization of the OAV287 genome further experimentation will be required to determine whether potential vaccine recombinants can be constructed for this adenovirus by making insertions into the pVIII/fiber intergenic region. PMID- 7778276 TI - Identification and analysis of a putative origin of DNA replication in the Choristoneura fumiferana multinucleocapsid nuclear polyhedrosis virus genome. AB - A recombinant plasmid containing the Choristoneura fumiferana multinucleocapsid nuclear polyhedrosis virus (CfMNPV) HindIII R fragment (m.u. 2.2-3.9) was shown to undergo CfMNPV infection-dependent DNA replication in Cf-124T cells. Replication of this DNA sequence was detectable by 24 hr p.i. and did not appear to have resulted as a consequence of recombination with the virus genome. Replication was inhibited by mimosine, an inhibitor of eukaryotic DNA replication. These data suggest that HindIII R of CfMNPV DNA contains an origin of DNA replication which we call ori1. HindIII R contains five GC-rich and three AT-rich regions and a 0.9-kb homologous repeat region 1 (hr1). Two short 440- and 740-bp contiguous sequences at the right end of the HindIII R fragment separately exhibited limited ori function. HindIII R subfragments with optimal ori activity contained a cluster of repeated and inverted sequences including nine copies of a 50-bp homologous repeat sequence (hr1a to hr1i) within hr1. The CfMNPV hr1 sequence was somewhat homologous with the homologous repeat (hr) of the putative Autographa californica MNPV (AcMNPV) replication origins. HindIII Y, another CfMNPV DNA fragment containing an hr sequence, hr3, also supported infection dependent DNA replication, suggesting that it too contains an ori. Although replication of a putative AcMNPV origin (HindIII Q) was detectable in CfMNPV infected Cf-124T cells, replication of CfMNPV HindIII R was not detectable in AcMNPV-infected Spodoptera frugiperda cells. PMID- 7778277 TI - Characterisation and mutational analysis of an ORF 1a-encoding proteinase domain responsible for proteolytic processing of the infectious bronchitis virus 1a/1b polyprotein. AB - Coronavirus gene expression involves proteolytic processing of the mRNA 1-encoded polyproteins by viral and cellular proteinases. Recently, we have demonstrated that an ORF 1b-encoded 100-kDa protein is proteolytically cleaved from the 1a/1b fusion polyprotein by a viral-specific proteinase of the picornavirus 3C proteinase group (3C-like proteinase). In this report, the 3C-like proteinase has been further analysed by internal deletion of a 2.3-kb fragment between the 3C like proteinase-encoding region and ORF 1b and by substitution mutations of its catalytic centre as well as the two predicted cleavage sites flanking the 100-kDa protein. The results show that internal deletion of ORF 1a sequences from nucleotide 9911 to 12227 does not influence the catalytic activity of the proteinase in processing of the 1a/1b polyprotein to the 100-kDa protein species. Site-directed mutagenesis studies have confirmed that the predicted nucleophilic cysteine residue (Cys2922) and a histidine residue encoded by ORF 1a from nucleotide 8985 to 8987 (His2820) are essential for the catalytic activity of the proteinase, and that the QS(G) dipeptide bonds are its target cleavage sites. Substitution mutations of the third component of the putative catalytic triad, the glutamic acid 2843 (Glu2843) residue, however, do not affect the processing to the 100-kDa protein. In addition, cotransfection experiment shows that the 3C like proteinase is capable of trans-cleavage of the 1a/1b polyprotein. These studies have confirmed the involvement of the 3C-like proteinase domain in processing of the 1a/1b polyprotein, the predicted catalytic centre of the proteinase, and its cleavage sites. PMID- 7778278 TI - A cis-acting viral protein is not required for the replication of a coronavirus defective-interfering RNA. AB - Mouse hepatitis virus (MHV), a coronavirus, generates defective-interfering (DI) RNAs of different sizes during passages at high multiplicities of infection. All MHV DI RNAs characterized so far contain an open reading frame (ORF) encoding a fused viral protein; in addition, DI RNAs with a long ORF have a competitive advantage over those with a shorter ORF. These findings suggest that DI RNA replication may require an ORF encoding a cis-acting viral protein. In this study, we used a naturally occurring DI RNA and inserted a 12-nucleotide (nt) amber-mutation linker at various positions to truncate the ORF. Most of the mutants replicated as well as the wild-type DI RNA, irrespective of the presence or absence and the length of the ORF in the RNA. Sequence analysis showed that all of the mutants retained the insertional mutations even after two viral passages in tissue culture, establishing that the mutant DI RNAs replicated. We have further introduced two 3-nucleotide substitutions of the first two AUG codons of the ORF, thus completely closing the ORF. This DI RNA replicated as well as the wild-type DI, but, after a single passage, the majority of the mutant RNAs was replaced by recombinant RNAs which contain a restored functional ORF. However, an additional insertion of a 12-nt amber-mutation linker downstream of the AUG substitutions prevented recombination, and the DI RNA still replicated. These data indicate that DI RNA replication does not require a DI-specific ORF encoding cis-acting viral proteins and that a 12-nucleotide insertion could prevent or delay the occurrence of RNA recombination, suggesting the importance of direct or indirect RNA alignment in homologous RNA recombination. PMID- 7778279 TI - Theiler's virus growth in murine macrophage cell lines depends on the state of differentiation. AB - Theiler's murine encephalomyelitic virus (TMEV) preferentially replicates in macrophages in the central nervous system of mice during the persistent phase of infection. Macrophages accumulate in demyelinating lesions and are evidently the primary cell to harbor virus. To investigate TMEV-macrophage interactions, we studied GDVII infection of three cell lines, M1, P388D1, and RAW264.7, representing various stages of macrophage differentiation/activation. GDVII virus was bound and internalized by RAW264.7 and P388D1 cells, but not by the precursor cell line M1. While infection of P388D1 cells produced a typical lytic cytopathology with marked loss of cellular activity to 10-20% of the uninfected control cells, RAW264.7 cells showed little cytopathology despite a decrease in cellular activity of 50-60%. Morphologic changes in infected RAW264.7 cells were similar to those occurring after cell activation. Although an infectious center assay showed that all P388D1 and RAW264.7 cells were infected, synthesis of viral RNA and proteins was markedly reduced and virus titers were restricted compared to permissive BHK-21 cells. Infected RAW264.7, but not infected P388D1, cells secreted tumor necrosis factor-alpha and nitric oxide. Therefore, depending on the differentiation and/or activation state, murine macrophages may be resistant to TMEV infection (M1), semipermissive and activated to secrete cytokines (RAW264.7), or semipermissive and not activated to secrete cytokines (P388D1). PMID- 7778280 TI - Localization of a domain on the paramyxovirus attachment protein required for the promotion of cellular fusion by its homologous fusion protein spike. AB - The promotion of membrane fusion by the paramyxovirus hemagglutinin-neuraminidase (HN) and fusion (F) proteins requires that they be derived from homologous viruses, suggesting the possibility that the promotion of fusion requires a virus specific communication between the two glycoprotein spikes. We have evaluated the ability of chimeric HN proteins, composed of domains from the HN proteins of two heterologous members of the group, human parainfluenza virus 3 (hPIV3) and Newcastle disease virus (NDV), to complement the F protein of each virus in the promotion of fusion. Specificity for the F protein of hPIV3 segregates with a segment composed of the transmembrane anchor and the first 82 residues of the ectodomain of its HN protein. Specificity of NDV HN for its homologous F protein is determined by a similar domain. These findings suggest that determinants specific to this segment of the attachment protein spike may be involved in the triggering of the fusion process. PMID- 7778281 TI - Gene organization of chicken anemia virus. AB - The genomic DNA of chicken anemia virus (CAV) was cloned and sequenced from a Japanese isolate CAA82-2. The nucleotide sequence of CAA82-2 isolate was 98% identical with that of the European Cuxhaven-1 strain (Noteborn et al., J. Virol. 65, 3131-3139, 1991). Nine open reading frames (ORFs) consisting of more than 100 nucleotides were found, i.e., four ORFs (CA1-CA4) on the plus strand and five ORFs (CA1R-CA5R) on the minus strand. These ORFs with the exception of CA4 are conserved between the two CAV isolates. All of these ORFs were expressed in Escherichia coli as fusion proteins with beta-galactosidase. By Western blot analysis, the CA2 and CA3 fusion proteins were found to react with CAV-infected chicken sera. Rabbit hyperimmune sera against the CA1, CA2, and CA3 fusion proteins were produced and tested their reactivity to CAV-infected cells. Two viral proteins with the apparent size of 54 and 16 kDa reacted with the antibodies against CA1 and CA3 fusion proteins, respectively. The 16-kDa protein, CA3, was suggested to be a major immunogen on CAV infection. PMID- 7778282 TI - The Capsicum L3 gene-mediated resistance against the tobamoviruses is elicited by the coat protein. AB - The L3 gene is responsible for the hypersensitive response in Capsicum plants against infection by tobamoviruses. The resistance conferred by this gene is one of the most effective so far described against tobamoviruses. Certain isolates of pepper mild mottle virus (PMMV) are the only tobamoviruses able to overcome the L3 resistance. Chimeric viral genomes between PMMV-S (to which L3 plants are hypersensitive) and PMMV-I (an L3 resistance-breaking isolate) led us to conclude that sequence variation within the coat protein gene of both isolates determines their different virulence in L3L3 plants. Furthermore, the results indicate that a single amino acid substitution, Asn to Met, at position 138 of the PMMV-I coat protein is sufficient to induce the hypersensitive response and localization of viral infection in C. chinense plants. Finally, the use of a mutant coding for a truncated coat protein (maintaining the Met138 coding sequence at the RNA level) demonstrates that a functional coat protein is required for elicitation of the L3 gene-mediated resistance. PMID- 7778283 TI - Sequence determination of human papillomavirus type 6a and assembly of virus-like particles in Saccharomyces cerevisiae. AB - Human papillomavirus 6a (HPV6a), the most abundant HPV6 subtype, was detected in a vulvar condyloma acuminatum. The complete genome of HPV6a was cloned, and its DNA sequence was shown to be over 97% identical to the HPV6b sequence. Of the eight open reading frames (ORFs) of HPV6a, only the imputed amino acid sequence of the major capsid protein L1 was identical to the corresponding HPV6b sequence; all other HPV6a ORFs showed amino acid changes compared to the HPV6b ORFs. The HPV6a L1 or the L1 + L2 ORFs were expressed in the yeast Saccharomyces cerevisiae. Self-assembly of the L1 capsid protein into virus-like particles (VLPs) was demonstrated both in the L1 as well as L1 + L2 coexpressing yeast strains. Copurification of the L1 and L2 proteins showed complex formation of the L1 and L2 proteins in the yeast-derived VLPs of coexpressing strains. PMID- 7778284 TI - The wild-type Autographa californica nuclear polyhedrosis virus induces apoptosis of Spodoptera littoralis cells. AB - Spodoptera littoralis cells infected with the Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) yielded significantly lower budded virus titers than Spodoptera frugiperda-infected cells and produced very low levels of polyhedrin. Relative to AcMNPV-infected S. frugiperda SF9 cells viral DNA replication was severely reduced in Spodoptera littoralis SL2 cells. Microscopic examination of SL2-infected cells revealed progressive cell blebbing starting at 6-8 hr postinfection and culminating in total cell destruction at 24 hr postinfection. The data suggested that AcMNPV-infected SL2 cells undergo apoptosis. The occurrence of an active apoptotic process in the infected cells was confirmed by: (1) observation of fragmentation of the cell nuclei stained with the specific fluorescent dye DAPI (4',6'-diamidino-2-phenylindole) and (2) the presence of low-molecular-weight DNA oligomers. Neither SL2 cells infected with S. littoralis nuclear polyhedrosis virus (SINPV) nor SF9 cells infected with AcMNPV, respectively, showed nuclear fragmentation or oligonucleosomal ladder formation. PMID- 7778286 TI - Identification, localization, transcription, and sequence analysis of the Choristoneura fumiferana nuclear polyhedrosis virus DNA polymerase gene. AB - The location of the Choristoneura fumiferana baculovirus DNA polymerase gene was determined by hybridization analysis using a probe prepared from the previously identified polymerase gene from the Autographa californica multiple nuclear polyhedrosis virus. DNA sequence analysis revealed that the Choristoneura fumiferana baculovirus DNA polymerase gene consists of 2970 base pairs encoding 990 amino acids (114.2 kDa). Transcriptional analysis demonstrated that overlapping transcripts of 3.2 and 4.6 kb, first detected at 6 hr postinfection, potentially coded for the DNA polymerase gene. The major transcription starts sites, identified at 6 hr postinfection, mapped to baculovirus consensus early start sites CGTGCTCA and CAGT. The relatively low level and late initiation of the DNA polymerase gene coupled with our previous data on the temporal control of DNA replication and late gene synthesis (Liu and Carstens, 1993) suggests that the low virulence of the spruce budworm baculovirus may be related to the regulation of its gene expression at the transcriptional level. PMID- 7778285 TI - Genetic polymorphism in the rabies virus nucleoprotein gene. AB - In an attempt to compare intrinsic and extrinsic genetic diversity of the lyssavirus genotypes, 69 rabies virus isolates from various part of the world were partially sequenced and compared to 13 representative isolates of the 6 lyssavirus genotypes. The analysis of their phylogenetic relationships, performed on the complete nucleoprotein (N) coding gene (1350 bases), established that the rabies virus isolates all belonged to genotype 1 and that at least 11 phylogenetic lineages could be identified in accordance with their geographical localization and species of origin. These lineages diverged mostly by the accumulation of synonymous mutations. Stabilizing selection, possibly related to host specificity, limits amino acid sequence and antigenic drift. Analyses were also performed either on the highly variable 400-base region coding for the amino terminus of the N protein or on the 93-base noncoding region corresponding to the 3' end of the N mRNA, the intergenic N-phosphoprotein (M1) region, and the 5' end of the M1 mRNA. These shorter nucleotide sequences were shown to provide phylogenetic data suitable for the completion of large epidemiological studies, but with less robustness. This latter noncoding sequence, despite a 3.1 times higher mutation rate than its adjacent coding N gene, followed a parallel evolutionary pattern. PMID- 7778287 TI - Identification of S71-related human endogenous retroviral sequences with full length pol genes. AB - The human genome contains sequences related to the simian sarcoma-associated virus SSAV. One of these endogenous retroviral elements, S71, is truncated in the pol gene and carries an insertion of a solitary HERV-K LTR. Using a PCR approach we have now identified further S71-related retroviral elements that lack the HERV K LTR insertion and contain a full-length retroviral reverse transcriptase. Two of these sequences, pCRTK1 and pCRTK6, were cloned and further characterized. Clones pCRTK1 and pCRTK6 showed between 85 and 90% nucleotide homology to each other and to S71 within the "tether" region of the pol gene, indicating that pCRTK1 and pCRTK6 clearly belong to the S71 subgroup of C-type-related human endogenous retroviral elements. Some point mutations inactivating the reverse transcriptase are located at the same positions in pCRTK1 and pCRTK6. Therefore, we assume that these S71-related elements were dispersed in the human genome by reintegration as defective proviruses, probably using enzymes for retrotransposition provided in trans by other retrotransposons or by cellular genes. Examination of the presence of S71-related elements in apes and Old World monkeys revealed that the deletion of reverse transcriptase sequences in S71 has occurred in the lineage of primates prior to the insertion of the HERV-K LTR. PMID- 7778288 TI - Comparative pathogenesis of Autographa californica M nuclear polyhedrosis virus in larvae of Trichoplusia ni and Heliothis virescens. AB - We compared early viral pathogenesis and dose-mortality relationships for larvae of two highly susceptible hosts, Trichoplusia ni and Heliothis virescens, using a construct of AcMNPV containing the lacZ reporter gene. Larvae were inoculated either as newly molted fourth instars (4(0)) or 15 hr after the molt (4(15)). In 4(0)-inoculated larvae, first lacZ expression was detected in the midgut epithelium of T. ni at 4 hr postinoculation (hpi) compared to 18 hpi in H. virescens, and systemic infections were initiated from tracheole cells servicing the midgut epithelia beginning at 12 and 20 hpi, respectively. The longer viral tenure within the midgut and the slower progression of systemic infections within H. virescens ultimately contributed to its longer time to death. For 4(0) inoculated H. virescens, proportions of lacZ-expressing larvae increased from 18 hpi until the onset of the molt to the fifth instar at 36 hpi; at this time point, the proportion of signaling insects equaled the final larval mortality. Viral infections within the midgut epithelium of H. virescens were lost during the molt to the fifth instar. Dose-mortality relationships suggested that the peritrophic membrane provided little protection from AcMNPV infections for either species. PMID- 7778289 TI - Immune responses to nucleic acid vaccines to rabies virus. AB - A plasmid vector expressing the full-length rabies virus glycoprotein (G protein) under the control of the simian virus 40 (SV40) promoter has previously been shown to induce upon intramuscular (i.m.) inoculation into mice a specific B- and T-cell-mediated immune response and protection against challenge with a virulent strain of the virus. Here we tested two parameters that might affect the efficacy of this DNA vaccine. First, we replaced the SV40 promoter of the original vector with the early promoter derived from cytomegalovirus leaving all other parameters of the plasmid intact. Although upon transfection in vitro the two vectors showed a striking difference in their ability to cause stable expression of the rabies virus G protein, upon i.m. inoculation into mice both constructs induced comparable immune responses. Second, we constructed a vector that induces expression of a secreted form of rabies G protein by inserting a stop codon just upstream of the transmembrane domain of the rabies G protein gene. The immune responses to the DNA vaccines expressing the two different forms of the G protein, secreted and membrane bound, were compared and found to be similar in magnitude. The long-term effect of DNA vaccination was also investigated especially with regard to adverse immunological reactions such as the induction of unresponsiveness against rabies virus and the development of antibodies to DNA. DNA vaccination was found to induce long-lasting immunity to rabies virus without apparent negative side effects such as development of T cell tolerance or generation of anti-DNA antibodies. PMID- 7778290 TI - Mutated forms of human cytomegalovirus glycoprotein B are impaired in inducing syncytium formation. AB - Human cytomegalovirus (HCMV) glycoprotein B (gB) promotes virion entry into cells by fusing the virion envelope with the cellular membrane. We recently reported that UB cells (U373 glioblastoma cells constructed to produce HCMV gB constitutively) form multinucleate syncytia that are dependent on the density of gB in the plasma membrane. In this report, we describe the properties of a clonal cell line, UB31-B3, that expressed a spontaneously mutated form of gB which lacked the fusion-inducing function of the wild-type molecule, and three UB cell lines that were constructed to investigate the effect of specific mutations in gB on syncytium formation. Flow cytometry analysis with a pool of monoclonal antibodies (mAbs) showed that the UB cells contained a high density of gB, which was associated with the cell surface. Immune precipitation experiments with UB31 B3 cells showed that the mutant gB reacted with all of the mAbs to the ectodomain of gB but with none of those to the cytoplasmic carboxy terminus, and that it was 35 kDa smaller than wild-type gB. Nucleotide sequence analysis showed that a termination codon had been introduced after amino acid lysine at position 669 in the ectodomain of UB31-B3 gB, generating a truncated glycoprotein. UB31-B3 gB was not secreted into the medium and was stably anchored in the plasma membrane, which suggested that a hydrophobic stretch of amino acids from 629 to 652 in the ectodomain may serve as a membrane anchor for this truncated form. Analysis of the UB cell lines expressing deleted forms of gB showed that deletion of all or part of the cytoplasmic and transmembrane domains reduced or abolished syncytium formation. In contrast, deletion of a major neutralizing region in the ectodomain of gB did not alter syncytium formation. Results of these studies indicate that different regions of the gB molecule participate in syncytium formation. PMID- 7778291 TI - The baculovirus GP64 envelope fusion protein: synthesis, oligomerization, and processing. AB - The baculovirus GP64 envelope fusion protein (GP64 EFP) is a class I integral membrane protein that enters the secretory pathway and is oligomerized and extensively processed during transport to the plasma membrane. The kinetics of GP64 EFP biosynthesis, oligomerization, and processing in Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV)-infected Lymantria dispar cells were examined by pulse label, pulse-chase, and immunoprecipitation experiments. Relative rates of GP64 EFP synthesis in OpMNPV-infected L. dispar cells were examined at various times throughout the infection cycle. Using pulse labeling and immunoprecipitation, GP64 EFP synthesis was detected within 2 hr p.i., and the maximal rate of synthesis was observed in the period of 24-26 hr p.i., a time coincident with the onset of high level production of budded virus in OpMNPV infected L. dispar cells. To determine the oligomeric structure of GP64 EFP, a soluble form of OpMNPV GP64 EFP was produced and examined by a combination of gel filtration chromatography, nonreducing SDS-PAGE, and mass spectrometry. Oligomeric GP64 EFP was identified as a trimeric molecule, that migrates as two discrete bands on nonreducing SDS-PAGE. Pulse-chase studies, performed at both early (12 hr p.i.) and late (36 hr p.i.) stages of the infection cycle, showed that GP64 EFP oligomerization is complete within 15 min after synthesis. Efficiency of oligomerization however was relatively low, with less than 33% of the synthesized GP64 EFP converted to trimers. The majority of monomeric GP64 EFP remaining in the cell appeared to be degraded within 30 to 45 min after synthesis. Analysis of the kinetics of carbohydrate processing at early (12 hr p.i.) and late (36 hr p.i.) times postinfection showed that for both early and late phases of infection, carbohydrate was rapidly added, and processing began between 10 and 20 min after GP64 EFP synthesis. Although carbohydrate processing was completed within approximately 90 min after synthesis during the early phase, the same process required approximately 150 min during the late phase. Thus, carbohydrate processing appeared to become less efficient as infection progressed. These studies thus show that GP64 EFP undergoes a rapid but inefficient oligomerization step that results in a homotrimeric structure for GP64 EFP. While carbohydrate addition is rapid, carbohydrate processing requires prolonged periods of time (with half-times of 45 to 75 min) and appears to become less efficient during the late phase of the infection. PMID- 7778292 TI - cis-acting regulatory elements in the bovine immunodeficiency virus long terminal repeat. AB - Functional cis-acting regulatory elements in the bovine immunodeficiency virus (BIV) long terminal repeat (LTR) were identified by deletion mapping and nuclear protein gel shift analysis using three BIV-infectible cell lines, Cf2Th, BLAC-20, and EREp. Deletion mapping studies indicated that putative NF-kappa B, GRE, AP-4, AP-1, CAAT, and ATF/CRE transcription factor elements positively contribute to LTR-directed gene expression in each cell line both in the presence and absence of the viral transactivator Tat. Sp1 and overlapping AP-3 and retroviral core enhancer elements had variable effects on LTR-directed gene expression depending on cell type and presence or absence of Tat. In addition, a sequence spanning the LTR U5 region and the untranslated viral leader was strongly repressive in all cell lines. Tat transactivated the LTR 25-fold over basal levels in a TAR dependent manner in Cf2Th cells. In contrast, Tat transactivated the LTR only 2.5 fold over basal levels in EREp and BLAC-20 cells in a TAR-independent manner. Probes for putative NF-kappa B, GRE, Sp1, AP-4, AP-1, overlapping AP-3 and retroviral core enhancer, and juxtaposed CAAT and ATF-CRE elements specifically bound nuclear proteins from these three cell lines and HeLa cells, with the stoichiometry of binding being cell-type dependent. Probes for AP-4, AP-1, and juxtaposed CAAT and ATF/CRE elements exhibited greater protein binding with extracts from virally infected cells than with extracts from uninfected cells, suggesting that viral infection can modulate nuclear factor binding. The present studies indicate that several transcription factor elements in the BIV LTR have functional roles and that cell type can strongly determine the role they play in gene expression. PMID- 7778294 TI - Comparison of the response to T-cell activation by integrated HIV-1 and HTLV-1 LTR-lacZ vectors. AB - Human Jurkat T-cell clones containing stably integrated HIV-1 LTR or HTLV-1 LTR/lacZ vectors were studied to compare the responses of integrated LTRs to T cell activation. Responses were compared also with those obtained in parallel with Jurkat cells stably expressing lacZ under the control of the cellular enhancer element NF-AT of the IL-2 promoter. Activation induced via the cell surface TCR/CD3 complex or the CD28 receptor elicited responses from the LTR of HIV-1; however, HTLV-1 LTR-directed expression was not observed following triggering of these cell surface pathways. Mitogenic activation by elevation of intracellular calcium (Ca2+) levels along with protein kinase C (PKC) signals was required for optimal expression of the HIV-1 LTR and the NF-AT element; however, increased intracellular Ca2+ was inhibitory to PKC-mediated expression from the HTLV-1 LTR. Time course experiments revealed a sustained PKC-mediated response by the HTLV-1 LTR, which was detectable in the absence of Ca2+ as early as 6 hr following stimulation. In contrast to the HTLV-1 LTR, in time course experiments the HIV-1 LTR responded to stimulation by mitogenic activation of PKC in the absence and presence of Ca2+ and by antiCD3 with lacZ expression beginning as early as 3 hr poststimulation. These results suggest that the HTLV-1 LTR appears to be refractory to several cellular pathways which are upregulatory to the HIV-1 LTR. PMID- 7778293 TI - Degradation of CD4 induced by human immunodeficiency virus type 1 Vpu protein: a predicted alpha-helix structure in the proximal cytoplasmic region of CD4 contributes to Vpu sensitivity. AB - The HIV-1-encoded Vpu protein induces a rapid and specific degradation of CD4 molecules in the endoplasmic reticulum (ER). In this study, Vpu-induced degradation of CD4 in the ER was investigated by quantitative immunoprecipitation of CD4 following cotransfection of COS-7 cells with CD4 and Vpu expressors in the presence of brefeldin A, a drug that blocks protein transport from the ER to the Golgi complex. In order to precisely define the sequence(s) or structural element(s) in the CD4 cytoplasmic domain necessary for Vpu-induced degradation, a panel of deletion and substitution mutants in the cytoplasmic domain of CD4 was generated and analyzed. In agreement with previous reports, our deletion analysis indicates that a region encompassing amino acids 411 to 419 (KRLLSEKKT) in the cytoplasmic domain of CD4 was required to confer Vpu sensitivity. However, six specific substitution mutations within this region did not confer CD4 resistance to Vpu, suggesting that neither the amino acid sequence nor the charge of the amino acids in this region was critical to Vpu-induced CD4 degradation. A dileucine motif that is important for internalization of CD4 and Nef-induced CD4 down-regulation was also not required for Vpu-induced CD4 degradation. Interestingly, two substitution mutants (CD4EMKL and CD4MK407,11PP) located in a more proximal cytoplasmic region of CD4 abolished Vpu-induced CD4 degradation. Computer-assisted analysis of the substitution and deletion mutants conferring CD4 resistance to Vpu-induced degradation indicated that these mutations disrupted a putative alpha-helix formed in the proximal cytoplasmic region of CD4. Taken together, these studies strongly suggest that a structural element in the proximal cytoplasmic region of CD4 contributes to Vpu sensitivity. PMID- 7778295 TI - Sequence of the genome of lactate dehydrogenase-elevating virus: heterogenicity between strains P and C. AB - The complete nucleotide sequence of genomic RNA (14104 nt) of one strain of lactate dehydrogenase-elevating virus (LDV), LDV-P, is reported. It exhibits only about 80% nucleotide identity with the sequence reported for another LDV strain, LDV-C (Godeny et al., Virology 194, 585-596 (1993), and is 68 nucleotides shorter than the reported LDV-C sequence. The difference in length is largely due to the lack of a 59-nucleotide-long direct repeat in ORF 1a of the reported LDV-C sequence. Sequence analysis of a total of 1.4 kb of ORF 1a of LDV-C via reverse transcription/polymerase chain reaction (RT/PCR) technology failed to confirm the presence of this repeat in the LDV-C genome as well as of 24 deletions/insertions of single nucleotides that give rise to apparent transient reading frame differences between the LDV-P and LDV-C genomes and might have represented frameshift mutations. An additional 35 nucleotides in ORF 1a of the RT/PCR LDV-C products were the same as in the LDV-P rather than the reported LDV-C genome. The nucleotide sequences of the 5' leader and the 3' noncoding ends of the two genomes and the heptanucleotides involved in joining the 5' leader to the bodies of the subgenomic mRNAs were highly conserved or identical. The predicted LDV-P proteins, however, differed from those predicted for the LDV-C proteins between 25% for the ORF 2 protein and 1% for the ORF 7 nucleocapsid protein. All functional motifs of the ORF 1a and ORF 1b proteins were conserved. The ORF 1a protein possesses 11 potential transmembrane segments that flank the serine protease domain. PMID- 7778296 TI - Lack of pseudotype formation between human immunodeficiency virus type 1 and Epstein-Barr virus in productively coinfected B lymphoblastoid cell lines. AB - Human immunodeficiency virus (HIV) can form pseudotypes with other enveloped viruses, including herpes simplex virus, when the two viruses coinfect the same cell. Pseudotypes between HIV and Epstein-Barr virus (EBV) have not been described. We observed unusually high levels of HIV-1 replication in SCID mice transplanted with human peripheral blood mononuclear cells (hu-PBL-SCID mice) when the mice developed EBV-associated human B cell lymphoproliferative disease. If this enhancement of HIV-1 replication were due to pseudotype formation rather than direct infection of B lymphoblastic cells by HIV-1, the pseudotypes could pose a novel biohazard to laboratory workers. To assess whether HIV-1 and EBV can form such pseudotypes, we established and characterized CD4-positive B lymphoblastoid cell lines (LCL) that contained cells infected with both EBV and HIV-1. A high-titered virus pool from these LCL could induce HIV infection in the Burkitt's lymphoma (BL) line BJA-B, but not in the BL line Ramos. Infection of BJA-B was blocked by neutralizing antibody to HIV gp120 but not by neutralizing anti-EBV gp350. These experiments provide no evidence for pseudotype formation, suggesting a low risk for EBV:HIV pseudotypes in natural infection of humans or in human cells transplanted to SCID mice. PMID- 7778297 TI - Fusogenic determinants of highly cytopathic subtype D Zairian isolate HIV-1 NDK. AB - Phenotypic characterization of subtype B strains of human immunodeficiency virus type 1 (HIV-1) indicates that the major determinants of their cytopathogenicity and tropism are contained in the gene coding for the envelope glycoprotein gp120, namely in its variable regions V1, V2, and V3. Recombinant viruses derived from HIV-1 LAV, the subtype B prototype virus, and HIV-1 NDK, the Zairian subtype D virus highly cytopathic for CD4-positive lymphocytes, were used to elucidate genetic control of fusogenic functions in subtype D viruses. Our data demonstrate that multigenic determination of fusogenic properties is more complex in the subtype D than in clade B viruses. Variability in three regions of HIV-1 NDK genome correlated with formation of large syncytia. These regions consisted of the matrix protein, the C-terminal portion of vpr up to the C1 region of gp120, and the V1-V3 regions of gp120. Variability in the envelope glycoprotein but not in other regions of the HIV-1 genome was related to enhanced resistance of HIV-1 NDK to treatment of target cells with OKT4-A anti-CD4 MAb. Therefore, a different genetic control affects two aspects of HIV-1 fusogenicity: (i) variability in the envelope glycoprotein itself is sufficient to influence a virus-to-cell fusion at the virus/cell entry, and (ii) a more complex genetic function including genes of matrix protein and envelope glycoprotein is related to variability of cell-to cell fusion during formation of syncytium. PMID- 7778298 TI - A single amino acid changes enhances the fusion promotion activity of human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein. AB - Clinical isolates of human parainfluenza virus type 1 in our laboratory were found to induce significantly different degrees of syncytium formation in CV-1 cells. Sequence analysis of high- and low-fusion strains suggested that the hemagglutinin-neuraminidase (HN) protein was responsible for the differences in fusion activity. We exploited the strain differences to define the specific amino acid residues of the HN protein which were responsible for the low and high fusion activities. The HN proteins of the two low-fusogenic strains 8389 and 45785, and the highly fusogenic strain C35, were expressed in HeLa T4+ cells and their fusion promotion activities were compared. When coexpressed with C35 F, HNs from the low-fusogenic viruses were associated with much lower fusion activity than was C35 HN, suggesting that the HN proteins modified the fusogenicity of the viruses. To identify the region of the HN protein responsible for this difference, we constructed a series of chimeric HN cDNAs combining 8389 and C35 sequences. All chimeric HNs that contained C35 sequence in the central 36% of the protein exhibited high fusion promotion activity. Further analysis by site directed mutagenesis showed that a single Asn-to-Lys substitution at position 242 converted 8389 HN to a highly fusion-promoting molecule. Thus, the globular head of the HN molecule is involved in fusion promotion activity. PMID- 7778300 TI - Do hemagglutinin genes of highly pathogenic avian influenza viruses constitute unique phylogenetic lineages? AB - Avian influenza A viruses of the H5 and H7 subtypes periodically cause severe outbreaks of disease in poultry. The question we wished to address in this study is whether these highly pathogenic strains constitute unique lineages or whether they and related nonpathogenic viruses are derived from common ancestors in the wild bird reservoir. We therefore compared the nucleotide and amino acid sequences of the hemagglutinin (HA) genes of 15 H5 and 26 H7 influenza A viruses isolated over 91 years from a variety of host species in Eurasia, Africa, Australia, and North America. Phylogenetic analysis indicated that the HA genes of H5 and H7 viruses that cause severe disease in domestic birds do not form unique lineages but share common ancestors with nonpathogenic H5 and H7 viruses. These findings predict that highly pathogenic avian H5 and H7 influenza A viruses will continue to emerge from wild bird reservoirs. Another important question is whether H7 influenza viruses found in mammalian species are derived from avian strains. We included eight equine influenza viruses and one seal isolate in the phylogenetic analysis of H7 HA genes. We could show that the HA genes of both, the equine and the seal viruses, shared ancestors with avian H7 HA genes. This indicates that currently circulating H7 viruses with an avian HA gene may have the potential to adapt to mammalian species and to cause an influenza outbreak in the new host. PMID- 7778299 TI - Deletion of thymidine kinase gene attenuates channel catfish herpesvirus while maintaining infectivity. AB - A recombinant thymidine kinase (TK) gene deletion mutant of channel catfish herpesvirus (CCV) was constructed and compared to the parent virus for replicative ability in cell culture, for the ability to infect, replicate, and cause lethal disease in the channel catfish host, and for the ability to induce protective immunity in channel catfish fingerlings. There was no difference between parent CCV and the TK-negative mutant (CCVTK-) in viral production in cell culture. However, in immersion challenge trials, 100-fold more CCVTK- than parent CCV was required to kill similar numbers of channel catfish fingerlings. The attenuation was confirmed as a TK-associated characteristic in marker rescue; the revertant regained the pathogenic characteristic of the parent virus. When catfish were immersion challenged with equal amounts of CCVTK- or CCV, the levels of virus isolated from the posterior kidney were similar through the peak production period which occurred 4 days postinfection. Subsequently, CCVTK- levels decreased dramatically when compared to CCV levels. Exposure to CCVTK- induced protective immunity against challenge with a lethal dose of wild-type CCV. The degree of protection provided by CCVTK- was related to the dose of CCVTK given. This study demonstrates that the genetically distant CCV retains recombination properties and TK-associated attenuation properties of herpesviruses of higher vertebrates. Additionally, the unique characteristic of CCV containing two copies of the TK gene did not prevent the use of this gene as a selectable site of homologous recombination. PMID- 7778301 TI - Analysis of ALV-based packaging cell lines for production of contaminant defective viruses. AB - We have previously described avian leukosis virus-based packaging cell lines that express gag, pol, and env proteins from two transcomplementing genomes and produce helper-free stocks of retroviral vectors with different host ranges. In this report, we demonstrated that (i) despite the deletion of the psi packaging sequence, the packaging-defective transcomplementing retroviral transcripts were packaged into virions at a level that could reach 2.3% of a wild-type virus packaging level and (ii) despite deletion of the 3' LTR, these genomes were transferred along with the vector to target cells. As these genomes were also bearing a selectable gene, titers of the resulting contaminant particles could be estimated, depending on the cell line to be between 0 and 6 infectious particles/ml of supernatant. PMID- 7778302 TI - Mutations in the p53 tumor-suppressor gene are frequently associated with bovine leukemia virus-induced leukemogenesis in cattle but not in sheep. AB - To investigate the mechanisms of bovine leukemia virus (BLV)-induced leukemogenesis, we have examined the alterations of the p53 tumor-suppressor gene in sheep and in cattle. The sequences of the open reading frames as well as the intron/exon junctions of the ovine and bovine p53 genes were determined. Pathological samples were screened for the presence of p53 mutations using a single-strand conformational polymorphism assay. Five of ten BLV-induced bovine tumors harbored p53 mutations. In contrast, only one of seven samples corresponding to circulating leukocytes from cattle in persistent lymphocytosis showed an alteration of the p53 gene. Surprisingly, no p53 mutation was found among the 10 BLV-induced sheep tumors analyzed. Altogether, these data indicate that p53 mutations are linked to BLV-induced leukemogenesis in cattle at the transition to the lymphomic stage. These results also enlighten different molecular mechanisms involved in sheep and in cattle during BLV-induced pathogenesis. PMID- 7778303 TI - Fidelity of homologous recombination in vaccinia virus DNA. AB - The fidelity of homologous recombination in vaccinia virus (VV) DNA was examined by constructing a viral recombinant whose genome contained a copy of the Escherichia coli lac z gene in which the central third of the gene was repeated on either side of the VV thymidine kinase (tk) gene. In this virus, homologous DNA recombination and consequent excision of the tk gene were necessary to restore the open reading frame for beta-galactosidase and thereby to confer a lac z+ phenotype. Imprecise recombination was predicted to increase the frequency of lac z- virus. However, after several passages during which almost every viral genome underwent homologous recombination, the frequency of lac z- plaques was indistinguishable from that of a control virus that could express beta galactosidase without prior recombination. We conclude that homologous recombination in VV DNA occurs with perfect fidelity at least 99% of the time. PMID- 7778304 TI - Minimum origin requirements for linear duplex AAV DNA replication in vitro. AB - We have investigated the minimal requirements for a functional origin of DNA replication in an in vitro assay which requires the adeno-associated virus (AAV) Rep 68/78 protein. When a linear duplex template was used, initiation of one round of DNA replication was achieved when nucleotides 1-56 of the AAV inverted terminal repeat (in the flop orientation) were present at the terminus of the template. A terminal resolution site was not required. Deletion of an additional 11 nucleotides from the terminal repeat blocked the reaction. PMID- 7778305 TI - Cell-to-cell fusion, but not virus entry in macrophages by T-cell line tropic HIV 1 strains: a V3 loop-determined restriction. AB - T-cell lines chronically infected with laboratory adapted, T-cell tropic HIV-1 strains (RF, LAI, CBL-4, and NY5) induced syncytia after cocultivation with primary macrophages. Such fusion-competent strains, however, replicated inefficiently after cell-free infection of macrophage cultures. Evidence based on proviral DNA synthesis, pseudotype penetration, and a V3 loop mutation revealed that cell-free infection was restricted at a prepenetration stage in entry and controlled by envelope sequences. Our results suggest that primary macrophages are sensitive to cell-to-cell but not to virion-to-cell fusion induced by the envelope glycoproteins of several T-cell tropic HIV-1 strains. PMID- 7778307 TI - The value of individualism. PMID- 7778306 TI - Interaction of Sendai viral F, HN, and M proteins with host cytoskeletal and lipid components in Sendai virus-infected BHK cells. AB - We have studied the interaction of Sendai viral fusion (F), hemagglutinin/neuraminidase (H/N), and matrix (M) proteins with host cytoskeletal and lipid components in Sendai virus-infected BHK cells using two nonionic detergents Triton X-100 (TX-100) and octyl glucoside (OG). Our results show that while M protein acquired resistance to both TX-100 and OG extraction, F and HN exhibited insolubility only to TX-100 but not to OG. Furthermore, in the presence of high salt (1 M NaCl), M, but not F or HN, became TX-100 soluble. Both type I (F) and type II (HN) viral glycoproteins acquired TX-100 insolubility at a late stage during exocytic transport as they acquired endo H resistance. In addition, TX-100 insoluble F and HN exhibited a lighter density compared to TX-100 resistant M by flotation analysis. Using recombinant vaccinia viruses that express Sendai virus HN, F, or M protein individually, we observed that each viral protein (F, HN, or M) was independently capable of acquiring TX-100 insolubility in the absence of other viral components. These results would indicate that while Sendai viral F and HN became bound to TX-100 insoluble lipids, M protein bound ionically to TX-100 insoluble cytoskeletal components and not to TX-100 insoluble lipids. PMID- 7778308 TI - Emotions, coping, and psychological well-being in elderly people with arthritis. AB - Rheumatoid arthritis, the most destructive and crippling of all forms of arthritis, poses a number of stressful demands on individuals. In a sample of elderly women (N = 59) and men (N = 19) with rheumatoid arthritis, the relationship between social economic status, severity of impairment, sex, stress emotions, type of coping strategy, and psychological well-being was explored. Path analysis results indicated that higher social economic status was directly related to greater use of confrontive types of coping strategies. Severity of impairment had a direct, negative influence on psychological well-being, but sex was not an important factor. Optimistic coping strategies were used most often and emotive coping strategies the least. PMID- 7778309 TI - Christian patients' views of spiritual care. AB - The purpose of this qualitative study was to discover the essential structure of spiritual care by obtaining detailed descriptions of the phenomenon from those who have received such care. Data were generated through open-ended interviews with 10 Christian volunteers and analyzed using Colaizzi's phenomenological approach. Findings revealed that spiritual care was given and received in a context in which the recipient was vulnerable and receptive to spiritual care. Three theme clusters included enabling transcendence of the present situations for higher meaning and purpose, enabling hope, and establishing connectedness. Implications for nurse clinicians, educators, and researchers are discussed. PMID- 7778311 TI - Risking involvement with cancer patients. AB - The helping relationship has been identified by Brammer (1988) as central to the practice of nursing. This study explored the process of developing special relationships with cancer patients. Interviews were conducted with 32 nursing personnel. The grounded theory method of constant comparative analysis was selected for this investigation. An open-ended interview guide explored the difference between the usual relationships nurses had and the special relationships they formed with selected patients. A basic psychosocial process, "risking involvement" in special relationships with cancer patients, was identified. The willingness to risk involvement took the forms of resisting involvement or practicing involvement. PMID- 7778310 TI - Moral reasoning among professional caregivers in nursing homes. AB - This article examines the responses from a sample of Swedish nursing home staff workers to a hypothetical ethical conflict highlighting the issue of restraint. The responses were analyzed in two ways: first, Piaget's theory of moral development was used to differentiate between "autonomous" and "heteronomous" awareness, and second, the responses were analyzed from the perspective of ethical principles, that is, autonomy, beneficence, nonmaleficence, and justice. The findings indicate that autonomous ethical awareness took precedence over heteronomous ethical awareness. The dominant moral values were the principle of beneficence, followed by the principle of autonomy. PMID- 7778312 TI - Characteristics of intuitive nurses. AB - A description is provided of the process used to verify characteristics of intuitive nurses that had been reported in the literature. These characteristics supplied the framework for construction of the Miller Intuitiveness Instrument (MII) reported earlier (Miller, 1993). Evidence for validity of the MII was provided in the Miller (1993) study by examining factor analyses and correlations with the intuitive component of the Myers-Briggs Type Indicator (MBTI). The following characteristics were subsequently verified: Intuitive nurses are willing to act on their intuitions, are skilled clinicians, and incorporate a spiritual component in their practices. In addition, intuitive nurses express an interest in the abstract nature of things and are risk takers. Intuitive nurses prefer intuition to sensing (as reflected by the MBTI) as a way to take in information. They are extroverted and express confidence in their intuitions. Likewise, nurses who delay making decisions until all the information is in are more intuitive than those who make decisions abruptly. PMID- 7778313 TI - Structure and faculty perception of climate in schools of nursing. AB - The purpose of this descriptive study was to explore the relationship between dimensions of structure (i.e., centralization, formalization, and complexity) and climate in schools of nursing, using the framework of contingency theory. Data were collected from 111 full-time faculty from 11 baccalaureate and 7 associate degree schools of nursing in Minnesota accredited by the National League for Nursing. The findings indicated a significant relationship between structure and climate in the schools of nursing. Dispersion of influence throughout the school was associated with a more favorable climate. A higher degree of supervision by superiors was related to a less favorable climate. PMID- 7778314 TI - Comparison of subjects who fully versus minimally participated in a breast feeding study. AB - Sampling bias occurs in research when a large percentage of subjects who are eligible for the study refuse to participate. During Phase I of a two-phase multisite Mother-Baby Feeding Project, approximately 50% of the 235 potential participants at four of five sites declined to enter the study. This report compares subjects who fully participated with those who minimally participated and explores factors related to subjects' refusal to participate. Data regarding sociodemographic data, breast-feeding experience, and reason for refusal were collected from 92 subjects who declined to enter but agreed to minimally participate. The fully participating subjects had more education than those who participated minimally. However, the breast-feeding outcomes studied were similar for both groups. This provides support for generalizing additional study findings beyond the group of fully participating subjects when considering breast-feeding outcomes. Findings lend insight into the problem of subject recruitment that is not well-addressed in the nursing literature. PMID- 7778315 TI - Computer networks as a source of research subjects. AB - Acquiring access to subjects for research is a problem that confronts many nurse researchers. Methods commonly used for subject recruitment may provide an inadequate subject pool for successful study completion. Computer networks can be a viable alternative for subject recruitment through the use of on-line bulletin boards and support groups for many health-related issues. The use of an on-line network to augment the subject pool in one study is briefly described. Nurses are encouraged to use this technology as one creative way to recruit and access subjects in order to continue to be successful in the clinical research arena. PMID- 7778316 TI - [Prostaglandins and prostaglandin analogs: experimental studies on their effect of tumor metastasis]. AB - Metastatic tumor spread is regarded as the highest degree of malignancy of tumors and generally determines the prognosis. Before clinically detectable metastases are evident in distant organs, tumor cells interact with cellular and non cellular components of the host as they complete the multistep process referred to as the metastatic cascade. Many investigational drugs acting at different levels of the metastatic process were tested for beneficial effects on metastasis. Because of the influence of prostaglandins on host components essential for tumor metastasis, this group of a compounds was tested in model of tumor growth and metastasis. Prostaglandins of the E, D and J series inhibit growth of variety of tumor cells and cause a reduction of primary tumor growth in vivo. The antiproliferative action of prostaglandins of the E series seems to be related to an induction of differentiation, whereas prostaglandins of the D and J series mediate growth inhibition by a blockade of the cell cycle and an inhibition of RNA and DNA synthesis. There is no conclusive evidence that prostaglandins of the E, D and J series may specifically interfere with mechanisms of tumor metastasis. In contrast to the prostaglandins of the E, D and J series, prostacyclin has been shown to inhibit several processes involved in tumor metastasis, but without exerting a direct cytotoxic effect on tumor cells. Our own studies have shown that Cicaprost, a stable prostacyclin analogue, prevents metastasis if given continuously from the day of tumor implantation, and is also effective in reducing metastasis if treatment is begun following surgical removal of the primary tumor, when micrometastases are already present. PMID- 7778317 TI - [Stimulation of platelet mitogen-induced prostaglandin I2 synthesis in periodontal tissue of cyclosporin A treated patients]. AB - Cyclosporine A (CsA) is a highly potent immunosuppressive agent that has proven to be particularly useful in organ transplantation. Like phenytoin and the calcium antagonists, this drug may be associated with gingival hyperplasia. This study examined the interaction of platelet derived growth factor (PDGF) with prostaglandin I2 (PGI2)--a potent mediator in inflammation and bone resorption. PGI2 synthesis was examined by bioassay in gingival tissue from rats, rabbits and humans. Gingival tissue from CsA-treated patients generates less PGI2. PDGF causes a dose-dependent increase in PGI2 release in both CsA-treated and control subjects. The actual and percentage increase in PGI2 synthesis, however, was significantly higher in control tissue. While PDGF on the other hand modulated cellular proliferation, it causes on the other hand liberation of PGI2 from gingival tissue, thus interfering with its own action and further synthesis. If the PGI2 response is insufficient as after CsA therapy, the proliferative action might dominate. These findings therefore suggest an important pathogenetic role of PDGF and possibly other growth factors in CsA-induced gingival hyperplasia. "CsA gingivitis" seems to be a predominantly proliferative process, whereby inflammatory reactions appear only as a secondary phenomenon. PMID- 7778319 TI - [Counseling in smoking--therapy for smoking--help for the smoker]. PMID- 7778318 TI - The mechanism of anti-thrombotic, thrombolytic and fibrinolytic actions of camonagrel--a new thromboxane synthase inhibitor. AB - So far pharmacological consequences of inhibition of thromboxane A2 (TXA2) synthase by imidazole derivatives (e.g., camonagrel or dazoxiben) were linked to suppression of platelet activity. Here we report that in patients with peripheral atherosclerosis or in cats with extracorporeal thrombogenesis treatment with camonagrel is associated with activation of fibrinolysis or thrombolysis. These phenomena seem to be related to the camonagrel-induced shift in metabolism of prostaglandin endoperoxides from TXA2 to prostacyclin (PGI2), although in an in vitro model the involvement of the L-arginine/nitric oxide pathway cannot be excluded. In cats camonagrel (10 mg/kg i.v.) produced not only a fall in TXB2 but also a rise in 6-keto-PGF1 alpha and no change in cyclic-GMP plasma levels. This points to PGI2 rather than to nitric oxide as an in vivo mediator of camonagrel induced thrombolysis. The crucial role of endogenous PGI2 in the thrombolytic response to camonagrel in cats was evidenced by its blockade following pretreatment of animals with a megadose of aspirin (50 mg/kg i.v.) and lack of any effect on pretreatment with L-NAME (100 micrograms/kg/min, i.v.). Obviously TXA2 synthase inhibitors (e.g., camonagrel) and cyclo-oxygenase inhibitors (e.g., aspirin) antagonize each other in their anti-thrombotic actions and must not be administered at the same time. Furthermore, in patients camonagrel (800 mg orally) suppressed TXA2 generation by 99.5% and doubled the plasma level of 6 keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778320 TI - [Therapy for smoking: a challenge for the physician]. AB - Smoking cessation is an outstanding and absolute necessity. But there is less possibility of permanent cessation by the first treatment. Combined therapy (e. g. psychological and drugs etc) will reduce relapses. Frequent information of the public via the media is most important and improves the changes of lasting smoking cessation. No doubt smoking cessation has great relevance in health policy and should be supported by all institutions concerned. PMID- 7778321 TI - [Psychological and physiological dependence in smokers and there effect on motivation for smoking cessation]. AB - The typical onset of cigarette smoking is determined on various psychological and social factors. The period of experimental smoking may be followed by habituation. Habituation involves development of skill in inhalation and regulation of nicotine dose, becoming accustomed to the mood-altering and other pharmacologic effects of nicotine, and development of a pattern of conditioned reinforcement from smoking. Many smokers continue to smoke because nicotine helps them to regulate mood. The nicotine intake leads promptly and noticeable to pleasant, desired psychotropic effects. In the event of physical dependence, the occurrence of withdrawal symptoms results in renewed nicotine intake. Psychological and physiological dependence could be very different among smokers and this has important implications on the motivation for smoking cessation. Using the Fagerstrom Test for Nicotine Dependence (FTND) to assess nicotine dependence in a population 6.000 randomly selected Austrians were interviewed. 42% of men and 27% of women were found to be smokers. 3 groups of smokers differing in dependence can be described: 36.5% are nicotine addicted; 30.2% must be psychosocial dependent because they show nearly no sign of nicotine dependence; and there is a group between, difficult to classify them as more psychological or more nicotine addicted. PMID- 7778322 TI - [Women and smoking]. AB - Of the 300,000 deaths attributable to smoking among women in developed countries in 1985, 21% were coded to lung cancer, for example, 41% to cardiovascular diseases, primarily coronary heart disease and stroke, and 18% to chronic obstructive pulmonary disease. Overall, female deaths rates from lung cancer in developed countries increased by almost 200% between 1957 and 1987. Smoking and tobacco consumption is a health risk for women at all ages. All women, regardless whether they are pregnant, performing oral contraception or estrogen replacement should not smoke; if they are not able to stop on their own, appropriate counselling and therapy should be provided according to the state of the art. Women who smoke typically go through the menopause 2 or 3 years earlier than non smokers. Cigarette smoking to increase the risk of estrogen-deficiency diseases, as cardiovascular risk and postmenopausal osteoporosis. Many women want to give up smoking for a number of reasons, such as health, freedom from smoking dependence, financial worries and of course pregnancy. Women find it more difficult to quit than men because of lack of social support, more reliance on cigarette to cope with stress and anxiety and fear of weight gain. Although many women manage to refrain from smoking for a long, they may relapse in situations involving negative emotions, such as conflicts, stress, loss. Men however, tend to relapse in positive situations, such as social events. Smoking cessation programmes have to cover specifically women's need including basic health education, discussion of withdrawal symptoms, strategies to maintain non-smoking and prevent relapse, continuing group support, stress management, advice on weight management, nutrition, fitness and exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778323 TI - Nicotine chewing gum and nicotine patch. AB - The nicotine gum is a flexible dosing form that allows for self-titration of nicotine. In order to secure adequate use instructions and guidance are necessary. The patches are fixed dose systems with no possibility to adjust dose, generally or momentarily. Because of its convenience to use, patch may be the first choice in a general practice setting while gum may prove more effective in a cessation clinic setting where more time and experience is available. Using both patch and gum in combination a certain base level of nicotine is established with patch, often insufficient in itself, but with adding of gum the desire for smoking will be better controlled. PMID- 7778324 TI - [Smoking cessation in a rehabilitation center]. AB - Diseases related to smoking are of enormous social and medical importance and thereby justify great efforts in all areas of prevention. Apart from the general practitioner, the hospital probably provides the ideal setting to motivate smokers to give up smoking. In the past 5 years 656 patients participated in such a programme in our rehabilitation centre. After an average of 1 year 265 of these patients were interviewed about their smoking habits. 40% of them had completely given up smoking. As we can see, the long-term results are good. Programmes to help smokers to give up their habit are certainly necessary and have successfully been tested. PMID- 7778325 TI - [Smoking cessation in the hospital]. AB - The paper surveys methods, experiences and problems in our smoking cessation ambulance we run in our hospital since 1980. In smokers lung function tests showed more restrictive then obstructive ventilation problems. This is in opposite to international literature. Therapy was successful in 48%. PMID- 7778326 TI - [Smoking cessation at work exemplified by "action blanca casa", a project for smoking cessation in the D. Swarovski & Co., Wattens, firm]. AB - Recent studies about the efficacy of smoking cessation programs in the workplace have brought up to common difficulties. Only long-term-programs show remarkable effects on smoking habits of the workers. Presenting ongoing long-term strategies for open discussion can improve the design of more powerful cessation programs in the future. Our program as an important part of modern "human resources management" is demonstrated and the results after 18 months are discussed. PMID- 7778327 TI - [Smoking and prevention at the work site]. AB - Risk factors for smoking are seduction of apprentices, but also work monotony, stress and indolence. Model prevention programs for workers proved to be effective in combining individual (smoking, nutrition, blood pressure) and occupational risk reduction. A smoking cessation program at the workplace is a group dynamic process and has to include the protection of nonsmokers from ETS. With a new workers protection law Austria has started to improve the protection of nonsmokers at the workplace according to the EEA treaty. PMID- 7778328 TI - A better way to reduce AFDC costs. PMID- 7778329 TI - Do seatbelts save lives? PMID- 7778330 TI - Conjoint screening questionnaires for alcohol and other drug abuse: criterion validity in a primary care practice. AB - The US Preventive Services Task Force recommended that physicians use the CAGE questions to screen patients for alcohol abuse. A similarly brief screening instrument for abuse of other drugs is needed. Two conjoint screening questionnaires for alcohol and other drug abuse were adapted from the CAGE questions and the Short Michigan Alcoholism Screening Test (SMAST). For 124 patients of an academic, community family practice, the conjoint questionnaires and their forerunners were compared with DSM-III-R diagnoses of substance use disorders as measured by the Diagnostic Interview Schedule-Revised (DIS-R). The SMAST and its conjoint analog exhibited low sensitivity. The CAGE Adapted to Include Drugs (CAGE-AID) was more sensitive but less specific for substance abuse than the CAGE, especially when a reduced criterion score was employed. The CAGE AID was more sensitive than the CAGE for subjects of varying sex, income, and level of education, as well as most patterns of substance use disorders. The diminished specificity of the CAGE-AID may have been, at least in part, artifactual. The CAGE-AID holds promise for identifying primary care patients with alcohol and drug disorders. PMID- 7778331 TI - Necrotizing granulomatous cervical lymphadenitis associated with B lymphocyte abnormalities and a positive PPD reaction. AB - Sarcoidosis is a diagnosis often made by exclusion. We present a case of what we believe is sarcoidosis presenting as cervical lymphadenopathy. Complicating issues in this patient included B lymphocyte abnormalities, and a positive PPD reaction. The patient continues to be steroid dependent. This case illustrates the difficulties in diagnosis and management of sarcoidosis. PMID- 7778332 TI - Hypernatremic dehydration in breast-fed infants. AB - Three cases highlight the association between elevated breast milk sodium and hypernatremic dehydration in the infant. All three mothers, breast-feeding exclusively, had sodium levels in breast milk elevated significantly above normal. Severe hypernatremic dehydration in otherwise normal infants who are exclusively breast fed can be due to elevated sodium levels in breast milk. PMID- 7778334 TI - Working women and insurance. PMID- 7778333 TI - The costs of traumatic spinal cord and brain injuries in Wisconsin. PMID- 7778335 TI - The objectives approach to assessing quality care. PMID- 7778336 TI - [Chronic pancreatitis as an interdisciplinary concept]. PMID- 7778337 TI - [Biological effect of shock waves--more than "just" lithotripsy?]. AB - After their introduction into medicine for kidney stone lithotripsy, extracorporeal shock waves have gained an established or promising role in the treatment of bileduct, pancreatic and salivary stones during the last years. Treatment of gallbladder stones is possible in a large proportion of patients, yet is cumbersome. Beyond lithotripsy, treatment of pseudarthrosis by shock waves reveals positive results. The role of shock waves in the treatment of soft tissue pain is at present unknown. There is a potential for further therapeutic applications of shock waves since shock waves exert a strong biological effect on tissue which is mediated by cavitation. Experiments using shock waves for tumor therapy have shown some promising results, yet devices which generate other waveforms than lithotripters are probably better suited. Shock waves cause a transient increase in the permeability of the cell membrane, and this might lead to further applications of shock waves. PMID- 7778338 TI - [Development of chronic pancreatitis from acute pancreatitis: a pathogenetic concept]. AB - Clinically, alcohol-induced chronic pancreatitis is commonly indistinguishable from acute pancreatitis. A relationship between these two forms of pancreatitis has therefore been suggested. This article presents a pathogenetic model which views the development and course of chronic pancreatitis as a consequence of severe acute pancreatitis. PMID- 7778339 TI - [The natural course of chronic pancreatitis--pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease]. AB - The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a longterm observation of > 10 years, and severe exocrine and/or endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of the observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths. PMID- 7778341 TI - [Chronic pancreatitis with inflammatory enlargement of the pancreatic head]. AB - A number of patients with chronic pancreatitis develop an inflammatory enlargement of the head of the pancreas leading to complications such as common bile duct, duodenal, pancreatic duct, and/or vascular obstruction. The duodenum preserving pancreatic head resection has been developed to treat these lesions and to avoid a Whipple procedure in chronic pancreatitis. Between 1972 and 1992 280 patients (231 male, 49 female, mean age 44, range 22-76 years) underwent a duodenum preserving pancreatic head resection for chronic pancreatitis. The indication to operate was a cholestases syndrome in 50% of the patients, a duodenal compression in 36% and an obstruction of the portal vein in 16% of the patients. 94% suffered from pain, 53% had recurrent severe pain attacks and 72% had daily pain. Hospital mortality was 1.1% (3/280). Pancreatic fistula, leakage of pancreatic anastomosis and postoperative bleeding occurred in 4.6%, 1.8% and 3.2% of the patients, respectively. A relaparotomy needed 16 patients (5.7%). With respect to glucose tolerance in the early postoperative period 88% of the patients, showed no change in comparison with the preoperative glucose tolerance analysis. In a long-term follow-up (mean follow-up time was 3.7 years (3 months to 18 years)) 219 patients were included. The late mortality within the follow-up period was 5.0% (11/219). 90% of the patients had no or rare pain in the long term follow-up. 63% of the patients were full rehabilitated professionally. The duodenum preserving pancreatic head resection represents a new standard procedure which solves most surgical problems in chronic pancreatitis. It does not lead to diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778340 TI - [The Whipple partial duodenopancreatectomy--its value in the treatment of chronic pancreatitis]. AB - The surgical treatment of chronic pancreatitis is indicated only in the complicated disease. The aim is mainly the treatment of pain, of mechanical obstacles and to exclude suspicion of cancer. Between October 1972 and January 1993 713 patients with chronic pancreatitis were treated at the Surgical University Hospital in Mannheim. In 40% of the patients conservative treatment was continued or intensified. Only in 123 patients a Whipple operation was performed. The leading symptom was pain in these patients. We saw postoperative surgical complications in 14 patients (11.4%). One of them died due to an operative leak (0.8%). Late results are based on a median follow up of 4.8 years and showed a complete or substantial pain relief in 94%. 66% went back to work. 77% gained weight with an average of more than 10 kg. The rate of postoperative endocrine insufficiency was 10% (total 40%), of exocrine insufficiency 26 (total 51%). Late mortality was 11% and mostly caused by continued alcoholic abuse. Based on these results, the Whipple operation seems to be the best standardized method for surgery of the complicated chronic pancreatitis within the head of the pancreas. PMID- 7778342 TI - [The status of duodenum-preserving resection of the head of the pancreas in therapy of chronic pancreatitis]. AB - AIM OF THE STUDY: To evaluate the efficacy of duodenum-preserving resections of the head of the pancreas in the treatment of chronic pancreatitis this study was devised. So far studies on the natural course and the different therapeutic approaches have primarily focused on pain measurement in rough categories and hard data as mortality and morbidity. In this study the improvement of the quality of life was assessed to determine the therapeutic success of both procedures. PATIENTS AND METHODS: In a prospective randomized study 24 patients underwent either Beger's (n = 11) or Frey's procedure (n = 13) so far. 15 patients suffered from distal common bile duct stenosis, 2 from segmental duodenal stenosis, 4 from segmental portal hypertension, and one from pancreato pleural fistula. The quality of life questionnaire of the European Organization for Research and Treatment of Cancer was assessed before surgery and during follow-up. The multidimensional questionnaire incorporates functional scales (physical, cognitive, emotional, and social), symptom scales (fatigue, pain, dyspnea, loss of appetite, sleep disturbance, obstipation, diarrhea, nausea, and vomiting), and a global quality of life scale. Follow-up was 12 months in all patients. RESULTS: There was no postoperative mortality in neither group. Postoperative morbidity was 17% (n = 2 in either group). This included one transitory common bile duct stenosis, one bronchopneumonia, and two postoperative bleedings which were treated conservatively. The pain index was reduced by 94% in the Beger- and 90% in the Frey group. The physical status, working ability, emotional and social functioning, and global quality of life score had significantly improved by 46%, 50%, 69%, 60%, and 67% in the Beger group and by 38%, 50%, 64%, 80%, and 67% in the Frey group. CONCLUSION: The duodenum preserving resections of the head of the pancreas according to Beger and Frey are equivalently safe and effective. Both techniques result in a significant improvement of the patients' quality of life. PMID- 7778343 TI - [Intraoperative risks and early postoperative complications in surgery of chronic pancreatitis]. AB - 69 patients (1986-1991) who underwent conventional surgery for chronic pancreatitis (n = 42) or related pseudocysts (n = 27) were analyzed retrospectively. 17 patients underwent partial duodenopancreatectomy (pDPE), 13 pancreaticojejunostomy (PJ), 20 cystojejunostomy (CJ), 9 resection of the left pancreas and 10 other procedures. We evaluated especially time spent in hospital (pDPE:28,5d (mean), PJ:29d, CJ:22,3d, others:28,8d), duration of operation (pDPE:6h, PJ:4,6h, CJ:2,6h, others:2,6h), requirement for blood substitution (pDPE:3,2 units, PJ:3, CJ:0,8, others:1,9), postoperative surgical (pDPE:6%, PJ:15%, CJ:5%, others:29%) and nonsurgical (pDPE:0, PJ:0, CJ:15%, others:14%) complications, and operative mortality (0 in all groups). Conventional surgery for chronic pancreatitis and pseudocysts carries a very low mortality risk but may cause prolonged morbidity in a minority of cases. PMID- 7778344 TI - [Endoscopic therapy in chronic pancreatitis]. AB - In chronic pancreatitis obstruction of the pancreatic ductal system by strictures, stones or pseudocysts seems to play an important part in pathogenesis. Therefore, therapeutic efforts are directed mainly towards reestablishing a free flow of pancreatic secretion. Endoscopic techniques allow decompression of the organ by stenting or stone extraction, as well as evacuation and drainage of pseudocysts. Thus, interventional endoscopy offers safe and long lasting therapy for many patients suffering from chronic pancreatitis. This paper gives a review of the literature and reports on own clinical data. PMID- 7778345 TI - [Results of surgical therapy of acute pancreatitis]. AB - Operative treatment of acute pancreatitis was carried out in 143 patients. The disease was caused by bilestones in 68%, by alcohol in 23%, idiopathic in 8%, and by different reasons (postoperative, helminthic disease) in 1% of the patients. The severity of the disease was classified into the grades I to III according to Kummerle. The lowest rate of complications and lowest mortality rates were observed in operations performed within the first hours or after two weeks after the beginning of the disease. The alcoholic pancreatitis showed the lowest mortality rate (16%), despite of 81% of these patients suffering from the severe grades II and III. This may result from the decision in favour of early second look operations in these patients. PMID- 7778346 TI - [How urgent is an operation in enterothorax?]. AB - The emergency treatment of the enterothorax is problematic due to weak lung functions and unstable hemodynamics, and because it does not influence the stage of maturity of the lungs. By delayed operation children with a critical starting position have a greater chance to survive, after their condition has been stabilised by intensive care treatment. During the stabilising period we managed to decrease the FiO2 level below 50% and to decrease the pCO2 level to 43 +/- 13 mm Hg in our patients (n = 10). Furthermore we succeeded to raise the O2 degree of saturation from 72 +/- 13 to 89 +/- 9%. The pH level went up from 7,238 +/- 0,181 to 7,394 +/- 0,060. If the condition of the patients worsens during the stabilising period--in our patients the stabilising period was between 12 and 24 hours--immediate operation is indicated. We have no experience so far in using ECMO in such situations. PMID- 7778347 TI - [Necrosis of the ligamentum teres hepatis and the anterior abdominal wall in acute pancreatitis]. AB - The varying sites of extrapancreatic tissue necrosis in acute pancreatitis seldom include the anterior abdominal wall. In cases of liver enlargement causing a high portal pressure, the umbilical vein serves as a vent, shunting the portal blood through the teretic hepatic ligament to the anterior abdominal wall. Corticosteroids make the tissues even more susceptible to the activated pancreatic enzymes and are thus a contributing factor to the tissue necrosis. We describe a case of necrosis of the teretic hepatic ligament and the anterior rectus abdominis muscle following acute biliary pancreatitis. PMID- 7778348 TI - [Congenital diaphragmatic hernia with symptoms in adulthood]. AB - A left-sided diaphragmatic defect in the centrum tendineum of a 27-year-old female patient, who complained about dyspnea and hemoptysis, will be reported concerning symptoms, diagnostic procedure and operative therapy. This presumably congenital diaphragmatic defect caused an organ prolapse into the pleural cavity probably enhanced by an increased intraabdominal pressure during pregnancy and delivery. The defect was primarily closed after laparotomy. No plastic surgical reconstruction with autologous or homologous materials was necessary. PMID- 7778349 TI - [Bacterial clearance of the terminal ileum in relation to the ileocolic connection]. AB - The ecology of the (neo-)terminal ileum was investigated in three groups of mongrel dogs (group 1 to 3; 6 animals per each group) depending on the ileocolic connection and the resection of the terminal ileum. The efficacy of a stabilized nipple-valve-anastomosis (SNVA) was evaluated comparing the physiological ileocecal valve and the conventional end-end-anastomosis. The relations of the aerobic and anaerobic bacterial counts of all 18 dogs (group 0) preoperatively served as reference-values. Under this physiological condition the median counts were found to be lower in the ileum than in the colon, two logs for the aerobic bacteria and three logs for the anaerobic bacteria, confirming statistical significance (p < or = 0.05). The resection of the terminal ileum conserving the ileocecal valve (group 1) had no influence on the bacterial flora of the neoterminal ileum, whereas the limited resection of the ileocecal valve with ileocolic end-end-anastomosis (group 2) induced a bacterial colonisation of the terminal ileum. In contrast, following wide ileocoecal resection and replacement of the ileocecal valve by the SNVA (group 3) the bacterial counts were lower in the terminal ileum than in the colon: five logs for aerobic and seven logs for anaerobic bacteria. This difference was statistically significant within this group between ileum and colon and between ileum preoperatively and postoperatively (p < or = 0.05). In conclusion, the bacterial clearance of the (neo-)terminal ileum depends more on the retrograde barrier-function of the ileocecal valve or an appropriate mechanical substitute than on the propulsive motility of the ileum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778350 TI - [10 years quality assurance in perinatology]. PMID- 7778351 TI - [100 years radical abdominal operation of cervix carcinoma: in memory of Wertheim's predecessors]. AB - 1895 was a crucial year in the course of the development of abdominal radical surgery for effective treatment of cervical cancer. In March of 1895, Ries presented the rationale of modern radical hysterectomy and was the first to call for systematic removal of pelvic lymph nodes. Independently, Clark in Baltimore, Rumpf in Berlin, and Latzko in Vienna performed the first radical hysterectomies. This article is dedicated to the memory of the contributions by these four pioneers of surgical gynecology presented in 1895. PMID- 7778352 TI - [Causes of perinatal brain damage]. AB - The incidence of cerebral palsy has remained constant at 2 per 1000 life births in western countries through cesarean section and electronic fetal monitoring have been applied increasingly often since the last decades. There has been a shift towards prenatal causes and consequences of early prematurity. High risk deliveries (3% of all) should be performed only in specialized centers for perinatal medicine. For low risk deliveries local hospitals are more convenient and are traditionally well accepted in Germany. Perinatal hypoxia as a cause of perinatal brain damage is rare. Documentation of clinical symptoms of hypoxic ischemic encephalopathy is mandatory in these cases. To investigate regional risk factors of perinatal brain damage we propose to connect the data of the perinatal inquiries and of the examinations of preschool children directed by german law. PMID- 7778353 TI - [Interventional therapy of inferior vena cava thrombosis in pregnancy--use of a new kind of temporary vena cava filter]. AB - Several changes occur during pregnancy that cause hypercoagulability such as venous stasis, increased levels of clotting factors, and decreased fibrinolytic activity. Nearly half of all maternal mortality can be attributed to thromboembolic disease. Recurrent embolism from venous thrombosis in pregnancy constitutes a major diagnostic and management problem. Treatment of deep venous thrombosis by anticoagulation alone may not be sufficient to prevent fatal pulmonary embolism. Because pulmonary embolism is a potential preventable and treatable condition, early and accurate diagnosis and treatment are mandatory. Prevention can be obtained by the implantation of clips, umbrellas or vena cava filters. There are only a few reports of the use of permanent inferior vena cava filters in the prevention of pulmonary embolisation in pregnancy mostly using the Greenfield-Filter. We present the indication and efficacy of a new retrievable vena-cava filter (FCP 2002) inserted through the internal jugular veins in pregnancy in two patients, which enables them to continue pregnancy, resulting in a vaginal delivery of healthy infants near term. The safety and effectiveness of this filter-system suggests that the indication for its use might be liberalized to include prophylactic insertion of this device in patients at risk known for thromboembolic disorders. PMID- 7778355 TI - [Experimental microendoscopy of the milk duct system (ductoscopy)]. AB - According to recent reports, the microendoscopic lactiferous duct investigation (ductoscopy) could improve diagnosis in case of pathological nipple discharge. However, the description of a reproducible and reliable methodology, suitable for thorough evaluation of the lactiferous duct is missing so far. Therefore, the pressure study developed a procedure, that may serve now as an experimental basis for further clinical evaluation. Access to the mamillary duct is primarily gained using atraumatic flexible teflon catheters. Corresponding to the diameter of the duct, either a semirigid 0.87 mm fiberendoscope can be successfully introduced via a 1.2 mm catheter, or a flexible 0.50 mm fiberendoscope via a 1.0 mm catheter. A controlled distension using few milliliters of ringer's lactate is the prerequisite for clear visualization of the intraductal space and protection against iatrogenic wall lesions. Metal microtocars are available as prototypes. They carry a somewhat higher risk to perforate, but are advantageous when pointing at an intraductal structure and using the microtrocar as a mark for microdochectomy. PMID- 7778356 TI - [Tubal sterilization in the new unified Germany--results of a survey]. AB - A total of 4 statistical reviews of pelviscopic surgery had been issued in the Federal Republic of Germany until 1988. The five new federal states started such reviewing first in 1989 by quoting the number of tubal sterilization at 800. Our study, covering the period from May 31, 1991 to June 01, 1992 reveals an increase in pelviscopic surgery up to 20,000 with upward tendency. All 198 hospitals of the five new states were included in the inquiry and 133 of them took part in the survey. Out of 20,915 sterilization reported, 18,873 (90.3%) were performed by endoscopic surgery. Coagulation techniques such as monopolar and bipolar HF methods, the endocoagulation according to Semm, and Laser techniques were available for endoscopic tubal sterilization. Mechanical methods such as a clip or Yoon's ring were used in less than 10% and were therefore of limited practical importance. Severe complications were reported in 32 cases. PMID- 7778354 TI - [Effectiveness of beta-hydroxyethylrutoside in patients with varicose veins in pregnancy]. AB - Pregnancy is a critical risk for development of varicosis, therefore early detection and treatment are strongly recommended. In our study we examined 51 patients subdivided into three groups. One group underwent physical therapy (cold foot-baths in the morning an in the evening), the other group was administered beta-hydroxyethyl rutosides, and the patients of the third group had appeared only once for examination. Leg circumference and diameter of vein (by sonography) were measured, and the subjective criteria evaluated. In the group of patients who were additionally given drugs, a significant reduction of all parameters was found: leg circumference was reduced by 3% and diameters of veins were reduced by 15% on average, the reduction of the subjective criteria was by 34%. Provided the veins were prevented from further extension through progressive varicosis, apparent beneficial clinical effects can be achieved by administration of beta hydroxyethyl rutosides. PMID- 7778357 TI - Curative treatment of clinical stage II endometrial carcinoma. AB - In a retrospective study of 54 patients we compared three treatment policies of clinical stage II endometrial carcinoma: One group of patients (n = 29) was surgically staged with histological examination made at surgery and treated by abdominal total hysterectomy with bilateral salpingo-oophorectomy. In case of cervical infiltration by tumour, a pelvic node sampling was added. The second group was treated by radical hysterectomy (n = 9) and the third group of patients (n = 16) was treated by abdominal total hysterectomy with bilateral oophorectomy only. The median follow-up time was 68 months. The overall five year-survival was 64%. The overall five year-survival rates according to surgical procedure were not significantly different. The survival curves were significantly different from each other as were those according to surgical stage and age. In a multivariant analysis stage, grading and age proved to have an independent relation with the survival rate whereas type of surgical procedure, depth of myometrial infiltration and type of radiotherapy had no influence on survival. Intraoperative histological staging allows adaption of treatment to the true stage, thus minimising treatment-related morbidity. PMID- 7778358 TI - [Examination by image analysis for determining quantitative DNA parameters of serous papillary adenocarcinoma of the endometrium--a single case analysis]. AB - Serous-papillary adenocarcinoma of the endometrium are rare tumors. We describe DNA-parameters of such a tumor. Imprint-cytologies were taken from 6 different tumor sites (myometrial invasion and 5 additional tumor localizations) and subjected to image-cytophotometry in order to determine their DNA-parameters. All histograms showed an aneuploid DNA-pattern. The DNA-malignancy grade (DNA-MG) was 2.21 +/- 0.11 on median and the 5c exceeding rate (5c ER) was 15.37 +/- 4.17 on median. These results and the slight variability of DNA-pattern at the reported serous-papillary adenocarcinoma support the hypothesis of an own entity of this tumor. Additionally, the high values of DNA-MG and 5c ER confirm the well known aggressive behavior of this tumor entity. PMID- 7778359 TI - [Cystosarcoma phylloides of the breast--2 case reports]. AB - Two cases of Cystosarcomata phylloides (C. ph.) in the breast were reported. In the first one after excision of the palpaple tumour mass the histological examination revealed a fibroadenoma with signs of C. ph. in the excision margins. The reported high rate of local recurrence also in cases of benign tumour type and/or in situ remained tumour structures (stromal hyperplasia) gave the reason for a second operation procedure, an enlarged quadrantectomy. In the second case sarcomatic degenerated areas and a high rate of atypical mitotic figures were found (> 20 mitosis/10 HPF). Therefore an ablative surgery was recommended. PMID- 7778360 TI - [Therapy of extensive lymphangioma of the vulva]. AB - The lymphangioma of the vulva offers difficulties in differential diagnosis because of its wart-like appearance [7]. Is the diagnosis histologically confirmed, there often arise uncertainties about an adequate therapy [7, 2, 15]. By this case report these problems will be explained. Vaporisation with the CO2 Laser showed to be the predominant therapeutical procedure. PMID- 7778361 TI - [The cellular fatty acid composition of bacteria in the family Vibrionaceae]. AB - Vibrio cholerae strains, serovar O1, biovar eltor, subtype Ogawa, isolated from different sources, V. cholerae classica and NAG vibrios have identical cell fatty acid composition with the prevalence of hexadecenoic, hexadecanoic and octadecenoic acids. V. parahaemolyticus and V. alginolyticus fatty acid profiles, being identical, are similar to V. cholerae profile, differing from it mainly by a higher content of dodecanoic acid. The similarity of the fatty acid profiles of Aeromonas sp. and Vibrio strains is indicative of their phylogenetic relationship. The fatty acid composition of Plesiomonas shigelloides characterized by the presence of methylenehexadecanoic acid and at the same time by its similarity to that of Vibrio and Aeromonas in the content of the majority of fatty acids, confirms the position on the intermediate status of the genus Plesiomonas between the families Enterobacteriaceae and Vibrionaceae. PMID- 7778362 TI - [Bacterial, viral and fungal infections of the lungs in AIDS]. PMID- 7778363 TI - [The mechanisms of infection transmission in the light of new data]. PMID- 7778364 TI - [The problems of preventing the most important helminthiases in Russia]. PMID- 7778365 TI - [Clonality and the phase variability of bacterial species and their relationship to the manifestations of an epidemic process]. PMID- 7778366 TI - [Phages of halophilic vibrios]. AB - The morphology and antigenic properties of 34 phages of Vibrio parahaemolyticus and V. alginolyticus strains isolated from Black Sea water, as well as their range of lytic activity and specificity of action, have been studied. Most of these phages have been found to lyze both V. parahaemolyticus and V. alginolyticus strains. In addition, highly specific phages capable of lyzing only V. parahaemolyticus serotype O5:K15, have been detected. The latter fact is a precedent indicating the possibility of search for other typing phages and the development of the scheme for the phage typing of V. parahaemolyticus in future. PMID- 7778367 TI - [Natural killer cells in middle-aged and elderly tuberculosis patients]. AB - The immunological study of 76 patients belonging to two age groups (group 1 consisting of 46 patients aged 60-85 years and group 2 consisting of 30 patients aged 20-40 years) was made. For control, healthy persons aged 60 years and older (30 subjects) and 20-40 years (28 subjects) were examined. The study revealed that, in contrast to the tuberculosis patients of the younger age group, the old age patients exhibited a decrease in the activity of natural killer (NK) cells. The greatest decrease in the activity of NK cells was observed in patients with chronic fibrocavernous forms of tuberculosis (in comparison with other forms of tuberculosis). PMID- 7778368 TI - [The epidemiology and epizootiology of rabies on the territory of the former USSR]. AB - On the territory of the former USSR rabies is as infection with natural foci in the western and central regions. In the republics of Central Asia and Transcaucasia, in the North Caucasus the presence of natural foci of infection is combined with appearance of the foci of rabies, mainly among dogs, due to human activities. The existence of natural epizootic cycles of three years has been established, and the natural foci of rabies have been found to prevail in certain landscape zones: steppes, forest-steppes, tundra, forest tundra. A vast zone of northern taiga remained free from this disease. About half a million persons asked for medical assistance in connection with rabies annually, and about 50% of them received urgent antirabies treatment. Of the total number of persons asking for antirabies assistance, the proportion of rural dwellers was about 30%, while the majority of rabies patients were from rural areas (about 70%). During the period under study the incidence of this disease among humans did not show any tendency towards a decrease and constituted 0.01-0.02 cases per 1,000 persons. Of the total number of persons contacting this disease, only 30% went to a clinic for medical assistance. PMID- 7778369 TI - [The complex study of the epidemic situation and of the immunological structure of the population in brucellosis foci]. AB - As the result of the complex clinico-laboratory examination of 265 cattle breeders working on 5 farms where cases of brucellosis among agricultural animals had been detected, 62 persons (21.8%) were found to have the positive reaction to brucellosis. A strikingly high proportion (38.3%) of infected persons was found among the workers of a cattle-feeding complex. Out of 62 persons with the positive reaction to brucellosis, 32 had different clinical manifestations of the disease. Treatment for all persons who needed it was organized, the rest were placed under dispensary observation. Regular complex clinico-laboratory examinations of cattle breeders to brucellosis were recommended. PMID- 7778370 TI - [The interrelationship of the capacity for the expression of different serovariants of the Yersinia pestis capsular antigen with the degree of reduction of the lipopolysaccharide of the bacterial cells]. AB - The immunochemical study of the expression of different serovariants of Y. pestis capsular antigen in Escherichia coli HB 101, Salmonella minnesota R595 and Y. pestis EV recipient strains with different degrees of LPS reduction was made. Plasmids pFS1, pFBK7 and pFBK10 coding initial and serologically atypical variants of the capsular antigen were introduced into microbiol cells. Altered LPS structures were shown to have no influence on the serological specificity of the capsular antigen. Immunochemical activity was determined in the diffuse precipitation test, the passive hemagglutination test and the antibody neutralization test. Changes in the structure of LPS were shown to produce no effect on the serological activity of the capsular antigen coded by intact fra operon (plasmid pFS1). The transfer of hybrid plasmids pFBK7 and pFBK10 to recipient microorganisms led to the synthesis of serovariant Fl1 in recombinant strains with O-LPS, which was immunochemically different from serovariant Fl2 synthesized in strains with R-LPS. PMID- 7778372 TI - [The role of the outer membrane proteins, determined by the Shigella flexneri invasiveness plasmid, in inducing cellular immune reactions]. AB - Fractions of S.flexneri 2a 516 outer membrane proteins determined by plasmid pSF140 have been shown to possess immunomodulating activity and to be capable of influencing the intensity of hematopoiesis, manifested by the stimulation of endocolony formation, the increase of the amount of splenic colony-forming units in the marrow, the increase of the pool of proliferating splenic colony-forming units of the marrow and their intensive migration into the blood. Outer membrane proteins have been shown to produce an immunostimulating effect on the functional activity of effector B-lymphocytes shortly after their injection. On the contrary, S.flexneri 2a 516/4 pSF140- outer membrane proteins produce a less pronounced effect on hematopoietic stem cells and reproduce unspecific immunostimulating effect on the formation of B-cells, synthesizing antibodies to heterologous antigen. PMID- 7778371 TI - [Q fever in the western region of Ukraine]. AB - Multiple natural and mixed foci of Q fever have been revealed at the territory of six administrative regions of the western part of the Ukraine. Coxiella burnetii strains have been isolated from small animals and ticks, the specific features of their ecology in Poles'e and forest-steppe zones have been determined. The necessity of the study of natural foci of Q fever at not yet surveyed territories for at least 3-4 years has been substantiated. PMID- 7778373 TI - [The induction of an immune response to influenza virus antigens by anti idiotypic antibodies]. AB - The present investigation indicate that homologous polyclonal anti-idiotypic antibodies induce both humoral and cell-mediated immune response. Experiments on the exhaustion of immune sera with vaccine have revealed that anti-idiotypic antibodies induce not only specific antibodies to influenza virus antigens, but also antibodies to other epitopes of the globulin molecule of the anti-idiotype. Anti-idiotypic antibodies, when reintroduced into animals, induce the production of anti-influenza antibodies of the anamnestic type, but do not induce the formation of antihemagglutinins. The injection of influenza vaccine to animals, previously immunized with anti-idiotypic antibodies, induces the production of antihemagglutinins; an increase in the level of immune complexes and antibodies to anti-idiotype, i.e. anti-idiotypic antibodies, induces the development of immunological memory with respect to influenza virus antigens, including antihemagglutinins. PMID- 7778374 TI - [The adsorbed-DTP-m vaccination of children with allergically altered reactivity]. AB - Immunization and booster immunization with adsorbed DPT-m vaccine was carried out, respectively, in 45 and 15 children with different severity of the course of an allergic disease, each child receiving simultaneously individually prescribed complex drug therapy. The postvaccinal period took a relatively favorable course. General and allergic reactions and complications observed after the injection of the preparation did not hinder the continuation of the course of immunization, while the appearance of neurological reactions provoked doubts on the expediency of the repeated injection of this preparation. A decrease in the content of diphtheria and tetanus toxoids in one immunization dose did not lead to the decreased synthesis of specific antibodies. The present investigation showed the possibility of using adsorbed DPT-m vaccine with reduced antigen content in cases of both the remission of an allergic disease and the subacute course of such disease. PMID- 7778375 TI - [The immunological activity of Neisseria meningitidis lipo-oligosaccharide incorporated into liposomes]. AB - Immune response to lipooligosaccharide (LOS), isolated from group B N. meningitidis cell wall, was studied after its incorporation into liposomes. The adjuvant effect produced by liposomal LOS, more pronounced in comparison with that produced by native LOS, was observed after the injection of the preparation by different routes (intravenous, intraperitoneal and subcutaneous injections), but the highest level of response was achieved after the intravenous and intraperitoneal injections of the preparation. Experiments aimed at the study of the dynamics of plaque-forming cells and the level of antibodies after intraperitoneal immunization of CBA mice with LOS revealed that immune response to liposomal LOS was more intense and prolonged than that to the free antigen. Liposomal LOS induced genetically nonrestricted and T-independent immune response. This fact was confirmed in experiments on mice having different haplotypes, such as CBA (k), C57BL/6 (b), BALB/c (d) and in nude mice with congenital thymic aplasia. In addition, liposomal LOS induced mainly the accumulation of IgM and IgG and did not produce the effect of immunological memory. PMID- 7778376 TI - [The effect of substances produced by a strain of Streptococcus sp. Thom-1606 on phagocytic activity]. AB - Among the substances produced by Streptococcus sp. strain TOM-1606 two fractions having the opposite influence on the phagocytic activity of peritoneal macrophages of white mice were detected. The fraction corresponding to peptides with a molecular weight not exceeding 10 kD activated natural phagocytosis. As shown in our earlier works, this fraction also had the maximum antimicrobial activity. The fraction with a molecular weight of 70-100 kD inhibited natural phagocytosis, acting as an immunosuppressive agent. PMID- 7778377 TI - [The immunosuppressive activity of Streptococcus aureus peptidoglycan]. AB - The immunosuppressive activity of peptidoglycan, obtained from S. aureus was studied in mouse experiments on the model of delayed hypersensitivity (DH) to guinea pig antigens. The study revealed that PG suppressed DH, this action being linked with its insoluble fraction. The soluble part of PG did not suppress DH. Experiments with the use of immunosorbent demonstrated the existence of serological similarity between the active factor of the soluble part of PG and its insoluble part. PMID- 7778378 TI - [The determination of specific Pseudomonas aeruginosa antitoxins in commercial preparations of human immunoglobulin]. AB - The comparative study of the activity of P. aeruginosa specific antitoxins in 134 lots of commercial preparations of human immunoglobulin in parallel mouse experiments on the neutralization of the lethal effect of exotoxin and in ELISA made it possible to establish a high degree of correlation between their results and the possibility of using immunochemical assays instead of biological tests in the large-scale production of anti-P. aeruginosa immunoglobulin. PMID- 7778379 TI - [The effect of the level of lipid peroxidation and the pH value of a liposomal suspension on its antibacterial activity]. AB - Multilamellar phosphatidylcholine liposomes have been shown to possess antibacterial activity with respect to Pseudomonas aeruginosa and Staphylococcus aureus. An increase in the level of lipid peroxidation products in liposomal suspension as the consequence of the earlier oxidation of liposomal lipid leads to a considerable increase in the antibacterial activity of liposomes. The pH of the liposomal suspension has also an essential influence on its activity. If the pH of the suspension has acidic values, its antibacterial activity increases. The bactericidal action of liposomal suspension is more pronounced with respect to S. aureus, than to P. aeruginosa. PMID- 7778380 TI - [Anti-Escherichia antibodies in the blood sera from nonimmunized donors and in preparations of human immunoglobulin]. AB - The anti-Escherichia activity of 188 serum samples obtained from nonimmunized blood donors and 157 batches of the preparation of commercial normal human immunoglobulin were evaluated in the passive hemagglutination test with diagnostica containing E. coli antigens (serovars O2, O14, O26) and Kunin antigen, as well as Re-glycolipid Salmonella minnesota strain R595, used as sensitins. The study demonstrated that from sera of nonimmunized blood donors and from normal human immunoglobulin preparations 5-8% of batches containing anti Escherichia antibodies to E. coli lipopolysaccharide (serovar O2) in titers of 1:640 and more could be selected. The study revealed that certain anti Escherichia antibodies of commercial normal human immunoglobulin, to IgG. PMID- 7778382 TI - [The demonstration of the genes controlling enterotoxigenicity in Staphylococcus aureus strains by using the polymerase chain reaction]. AB - The selection and subsequent synthesis, according to the nucleotide sequences of S. aureus genes responsible for the expression of enterotoxins A and B, of highly specific primers for polymerase chain reaction Pcr were carried out with the use of the program "Primer". The optimum temperature conditions of polymerase chain reaction for all pairs of primers were selected. The method for the rapid determination of the enterotoxigenic properties of S. aureus strains by means of Pcr was proposed. The enterotoxigenic properties of several S. aureus strains were determined, which revealed that 3 clinical isolates had the gene of enterotoxin A in their genome, while laboratory strain FRI-722(H) carried the genes of enterotoxins A and B. PMID- 7778381 TI - [The lymphocyte proliferative response to Staphylococcus aureus antigen in mice with an opposite susceptibility to staphylococcal infection]. AB - The difference between the proliferative response of spleen cells to S. aureus cytoplasmic antigen on days 5 and 9 of the infectious process was shown in experiments of CBA and C3HA mice, opposite in their susceptibility to systemic staphylococcal infection. Hybrid mice F1 (CBA x C3HA) inherited a high level of proliferative response on day 5 (as in resistant CBA mice) and its low level on day 9 (as in susceptible C3HA mice). These data on genetic differences in proliferative response to S. aureus cytoplasmic antigen were confirmed in the test of the proliferation of lymph node lymphocytes taken from mice of these lines immunized with the above-mentioned antigen in Freund incomplete adjuvant into the pad of their paws 14 days before the test. PMID- 7778383 TI - [New methodological approaches to the use of the PHA reaction in determining anti Shigella antibodies]. AB - Pronounced correlation between the titers of hemagglutinating antibodies to different types of shigellae and other bacteria in healthy persons and in sick persons of control groups has been established. On the basis of this regularity a new approach to the use of the passive hemagglutination test in shigellosis, taking into account the ratio of antibody titers to different Shigella types, has been developed. This essentially increases the sensitivity and specificity of the test, thus making it possible to standardize its evaluation and permitting the effective diagnosis of shigellosis from the onset of the disease. PMID- 7778384 TI - [The effect of oral rehydration therapy on pancreatic function in patients with acute intestinal infections]. AB - The results of the study of the level of pancreatic hormones (insulin, glucagon, C-peptide and trypsin), carried out with the aim of finding out the character of relationship between hormonal disturbances and the state of carbohydrate metabolism, as well as the influence of oral rehydration therapy (ORT) with glucose-salt solutions on the function of the pancreas, are summarized. All subjects to be examined were divided into two groups receiving different kinds of ORT. The patients in group 1 (153 subjects) were treated with glucosolan and in group 2 (73 subjects), with sodium citrate in an amount of 2.5-5 lit. over the 6 hour period of treatment. The determination of the content of immunoreactive insulin, glucagon C-peptide and trypsin in the blood as the characteristics of the hormonal activity of the pancreas has made it possible to find out disturbances in the incretory and excretory activity of the pancreas in patients with acute enteric infections of different etiology. ORT with glucosolan and sodium citrate facilitates the restoration of pancreatic function in 65-70% of in patients with acute enteric infections of different etiology. PMID- 7778386 TI - [The theoretical problems of forensic psychiatric expertise in a civil trial]. PMID- 7778385 TI - [The Amben regulation of the intestinal microflora and macrophage functional activity in an experiment]. AB - The possibility of the correction of intestinal microflora disorders and the functional activity of macrophages in dysbiosis, caused by the intragastric administration of ampiox, with the use of amben (PAMBA), an inhibitor of proteolytic enzymes, was studied. Quantitative and qualitative changes in the main representatives of automicroflora, the functional activity of macrophages in the phagocytosis of 51Cr-labeled sheep red blood cells, the intensity of protein synthesis, the content of cathepsin D, acidic phosphatase and nitro blue tetrazolium activity were determined. The combined administration of ampiox and amben normalized quantitative and qualitative ratios of the main representatives of intestinal microflora, as well as the characteristics of macrophage functional activity, studied in this investigation. The administration of amben to intact animals was found to stimulate bifido- and lactoflora. PMID- 7778387 TI - [A comprehensive clinico-neurophysiological study of the efficacy of the pharmaceutical preparation glycine in acute ischemic stroke]. AB - In intensive care unit 226 patients underwent step-by-step clinical and neurophysiological investigation of glycin chemotherapy efficiency in the acute period of ischaemic stroke. Investigation included double-blind placebo controlled method, monitoring (by means of EEG, toposelective mapping of EEG, SSEP, transcutaneous cortical electric stimulation, ENMG) of changes of brain functional state after the first drug dose and course of treatment, analysis of dose-dependent action of the drug, posticchemic follow-up. It was found out, that usage of the drug glycin (daily dose 1-2 grams) in the combined intensive treatment of stroke provided for significant acceleration of regress of disorders of consciousness and other general and focal signs (in comparison with severity matched control group), and more complete and stable restoration of function to the end of acute period of the disease. PMID- 7778388 TI - [The amyotrophic lateral sclerosis syndrome--frontal-type dementia]. AB - The article presents analysis of clinical case of and review of literature on "ALS-dementia complex", a combination of ALS syndrome and dementia predominantly of frontal lobe type. The review of literature contains discussion on the problem of lobe dementia, analysis of relation of ALS-dementia syndrome and the following diseases: Alzheimer, Pick, Creutzfeldt-Jakob, Lewy bodies, Charcot (classic type), multisystem degeneration. Polymorphism of ALS-dementia complex and the possibilities of its differential diagnosis are considered. PMID- 7778390 TI - [The angioarchitectonics in the areas of greatest brain atrophy in Alzheimer's and Pick's diseases]. AB - Atrophic brain diseases (Alzheimer's disease, senile dementia, Pick disease, etc.) associated with grave dementia have clinical and neuroanatomical differences. The differences in angioarchitectonics concerned to the degree of vessel arborization, twisting, their direction, as well as congenital anomalies. These changed were more expressed in Alzheimer disease. In Pick disease predominated atrophic changes. PMID- 7778391 TI - [Synaptic plasticity and the glio-synaptic relationships of the rat hippocampus in age-related memory dysfunction]. AB - Qualitative and quantitative studies of structural changes of synaptic contacts and processes were performed in aged memory-non-impaired an aged memory-impaired rats compared to young rats in the stratum lucidum of the hippocampus. Aged memory-impaired rats (compared with young adults) showed alteration in the ultrastructure of mossy fiber expansions and the loss of axospinous synapses formed by them. These changes were more pronounced than in memory-non-impaired rats. There were no significant differences between aged memory impaired and aged memory non-impaired rats except for a significant decrease in volume density of postsynaptic density in axodendritic synapses formed by mossy fiber expansions in memory impaired animals. PMID- 7778389 TI - [Changes in the immunological parameters in Alzheimer's disease: their relation to disease severity]. AB - The peculiarities of the immune system in patients with Alzheimer's dementia (AD) and their relations with some clinical parameters were investigated. 21 patients with AD aged 51-70 and 16 age-matched healthy subjects were included in this study. The following parameters were examined: 1) total lymphocyte numbers, 2) the functional activity of T- and B-lymphocytes under conditions of stimulation by nonspecific mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM) and 3) the production of interleukin-1 (IL-1) and interleukin-2 (IL-2). A statistically significant decrease (p < 0.01) in lymphocyte number and significant increase of proliferative activity of T-lymphocytes, stimulated by PHA (when the small mitogen doses in the range of 1.25-2.5 mg/ml were used) were found in patients with moderate and severe dementia (p < 0.05, p < 0.01). No significant changes of lymphocyte proliferative activity were detected in patients with mild dementia. Some tendency for higher IL-1 production was found in AD patients, but it was not statistically significant. No changes of functional activity of B-cells and of production of IL-2 in AD patients were found in comparison with the control group. PMID- 7778392 TI - [The basic factors affecting outcomes in strokes]. AB - Outcomes in 1102 patients with 3 main types of stroke have been analysed to determine the significance of basic stroke outcome predictors. They are: type of the stroke, location of the focus, gravity of the patient's condition when the first aid is performed, spectrum of hospital facilities, diseases of the patient before and besides the stroke. A decrease of the mortality rate and optimal level of ADL score after stroke can be provided in cases when intensive care units general hospitals are the first step of treatment. PMID- 7778394 TI - [The topographic EEG mapping of patients with an organic brain lesion]. AB - Brain mapping was carried out in 50 patients with organic brain lesions (tumors, disturbances of vascular circulation, multiple sclerosis, consequences of brain trauma ets.) The parallelism between the severity of the organic brain lesion and the degree of bioelectrical activity disturbances has been discovered. In patients with brain tumors, consequences of the stroke, severe trauma and multiple sclerosis the focuses of pathological activity corresponded to location of the brain lesion. PMID- 7778393 TI - [Mossy fibers of the hippocampus in Alzheimer's disease]. AB - An ultrastructural study of changes in synaptic contacts and astrocytic processes of postmortem hippocampus was performed in 5 cases of Alzheimer's disease. Mossy fibres in the stratum lucidum were examined. Pronounced alterations included clustering of synaptic vesicles, membranous damage and multilamellar profiles in synaptic terminals. There were many hypertrophic astrocytic processes around synapses. The findings suggest that the ultrastructural alterations in mossy fibers expansion, and the disturbance of glio-synaptic relationships might contribute to memory impairment in Alzheimer's disease. PMID- 7778395 TI - [Triplet expansion analysis--a new molecular genetic method for studying the mechanism of mutations in neurogenetics (exemplified by Huntington chorea)]. PMID- 7778396 TI - [The Gerstmann-Straussler syndrome: new diagnostic possibilities]. AB - On the basis of clinical picture of the disease, data of CT, MRT, psychological study, original laboratory investigation aimed at indication of changes in transposed neuroglia cells induced by the causal agent of subacute spongious transmissible encephalopathies, the diagnosis of patient K., 49 years old, was considered to be: syndrome of Gertsmann-Straussler [correction of Herstmann Streussler]. Duration of the disease was 2 years. The case was sporadic. The history of the problem, modern views on etiology, pathogenesis of preventive measures are presented. PMID- 7778397 TI - [The characteristics of the cognitive defect in patients with different variants of late paranoia]. AB - Evoked cortical activity in response to acoustic stimuli (oddball paradigm) was studied in patients with different paranoid disorders. The analysis covered the N150 negative wave and positive complex P300. In patients with paranoid schizophrenia and paranoid form of involutional psychosis cortical responses to the stimuli and cortex effects were not recorded. Such cognitive deficiency is believed to be typical for schizophrenia. PMID- 7778398 TI - [The psychological and psychiatric study of children living in Kaluga and Bryansk provinces, Russia (the aftermath of the Chernobyl accident)]. AB - According to WHO project "Brain Damage in Utero" in the framework of the screening phase of the programme, 1025 children (725 in experimental group Novozybkov and Klintsy towns of Bryansk region; 300 in control group--Obninsk town of Kaluga region) and 600 parents (300 in experimental group and 300 in control group) were studied using standardized methods of psychological psychiatric assessment (Draw-a-man test, British picture vocabulary test, Raven coloured matrices, Parental and teacher Rutter Scales, CHQ-28, Verbal subtest of Wechsler test) for potential psychological and psychiatric effects of Chernobyl accident on child's intelligence, behavioural and emotional state, mental health of parents and parental intellectual level. The following results were obtained: comparison of verbal IQ scores in children revealed a 6-fold increase of these values in experiment group. Comparison of nonverbal IQ scores in children revealed that these values are 4 times higher in experimental group. Comparison of scores according to Rutter parental and teacher scales revealed that emotional and behavioural disorders are 1.5 times more prevalent in children of experimental group. All the above differences were statistically significant. Comparison of CHQ-28 scores was indicative of relative prevalence of these values in parents of experimental group, but there was no statistically significant difference between such score in experimental and control groups. Comparison of scores of parental IQ showed relative prevalence of these values in experimental group. The results obtained can not be completely estimated without thorough identification of individual doses received by mothers and their children. Only after obtaining these data it will be possible to solve the problem of dose effect. PMID- 7778399 TI - [Electroencephalographic markers and the computerized evaluation of the severity of depression]. AB - In 24 patients with moderate, pronounced and extremely pronounced (according to Hamilton Scale) sings of depression EEG of frontal, temporal, parietal and occipital areas of brain hemispheres were investigated. Control group consisted of 24 normals, being under supervision for a year. 4 types of EEG patterns (matrices) probabilities of changes were selected; those parameters correlated with severity of depression and stage of depressive phase. A cyclic character of transformation of organization of bioelectric processes during the disease has been demonstrated: orders of matrices changes in cases with reduction and aggravation of depressive signs were opposite. Linear discriminant functions or EEG markers, significantly different for groups of patients with different severity of depression, have been obtained. It allowed to create the computer based system of evaluation of depression severity with high diagnostic accuracy. PMID- 7778400 TI - [The catamnesis of patients with stenosis of the internal carotid artery who have undergone carotid endarterectomy and of unoperated patients]. AB - Investigation of catamnesis of 100 patients with atherosclerotic carotid artery stenosis (50 were operated and 50--non-operated) revealed, that in some cases carotid endarterectomy prevented repeated cerebrovascular disorders and had prophylactic significance. The frequency of repeated stroke in the group of non operated patients was 3 times higher than in the group of operated patients. In operated cases no more TIAS were observed, but they persisted in non-operated cases. PMID- 7778401 TI - [The economic aspects of the activities of a mental health service]. AB - Integral economic loss of the society, connected with mental disease, were calculated by the author and presented. The author determined "direct" and "connected" state costs for psychiatric patients, and the volume of non produced national income (indirect costs) because psychiatric patients with temporal or constant disability are excluded from producing process. Financial state of psychiatric hospitals in Moscow was analysed and reserves for improvement of money spending were found out. Calculations of expenses of admission of patients with different diseases to Psychiatric Hospital N 1 by P.P. Kashenko in 1988 were performed. Principles of financing of psychiatric hospitals on the basis of clinical-statistic groups are discussed. The method of determination of prices for medical and diagnostic services to patients is presented. PMID- 7778402 TI - [The clinico-social structure of the geriatric patient contingent of a psychiatric hospital]. AB - In order to study the problem of setting down of mental patients in geriatric units of a mental hospital, a clinico-epidemiological one-day overall study was conducted. It appeared that among 600 patients of a provincial mental hospital 124 (20.6%) were residents of such units. Long-term stayers (over 5 years) comprised a group of 25 patients (20.2%). Most of them were those in whom the onset of schizophrenia took place at young age. The second (according to the number) group consisted of patients with mental disturbances due to organic brain disorders. This group was characterized by an unfavourable previous social status. 80% of them had no place to live in, no close relatives. The authors think it necessary to set up special units of a hostel type for rehabilitation of "precipitated" patients within the framework of a mental hospital. PMID- 7778403 TI - [The diagnosis and treatment of neurosarcoidosis]. AB - In 14% of patients with respiratory tract sarcoidosis granulomatous lesions were found in the central nervous system. Clinical classification of neurosarcoidosis was developed which included specific granulomatous forms: CNS arachnoiditis and perivasculitis, sarcoid myositis, as well as nonspecific forms (vasoautonomic dystonic syndrome, angiotrophoneurosis). Diagnostic and therapeutic techniques are presented. PMID- 7778404 TI - [Familial paroxysmal ataxia]. AB - The paper provides clinical and paraclinical findings on 3 patients from one family (two brothers and father) suffering from familial paroxysmal ataxia. The authors observed psychosensory disturbances not typical, according to the literature for attacks of ataxia, dysarthria and nystagmus. The evidence obtained on cerebral and spinal evoked potentials made it possible to diagnose multilevel impairment of nervous impulse conduction in the somatosensory system which may be due to metabolic disturbances underlying the disease. PMID- 7778405 TI - [Binswanger's disease and the problem of vascular dementia: on the centenary of its first description]. PMID- 7778406 TI - Electrophysiological evidence of Ranvier node clustering in human sensory nerve fascicles. AB - Thin concentric needle electrodes were used to explore intact median nerve fascicles in human subjects. In particular, the presence of single units, probably recorded from nodes of Ranvier, was studied in different parts of a fascicle. Single-unit activity in myelinated fibers was rarely found at numerous sites. In many other intrafascicular areas, a substantial number of single units could be discriminated in the same or nearby recording sites with the same technique. To account for the neurophysiological results, stochastic models and statistical tests were developed to test various hypotheses concerning intrafascicular nerve fiber arrangements. The acquired data suggested both an intrafascicular modality grouping of nerve fibers and a simultaneous clustering of the Ranvier nodes of these fibers within very restricted areas of a fascicle. It was further concluded that the yield when searching for units in different types of nerve preparations may depend upon the ultrastructure of the explored nerve segments. PMID- 7778407 TI - The influence of spatial summation on human tactile directional sensibility. AB - Spatial summation is known to influence the magnitude of sensation for stationary cutaneous stimuli. Yet analysis of moving stimuli may also be pertinent, since most stimuli that attract our attention involve movements over the skin surface. The present investigation dealt with the importance of spatial summation for the appreciation of the direction of motion for moving stimuli. The ability to detect the direction of motion was tested on the radial surface of the forearm with the two-alternative forced-choice method. Stimulation was performed with a rolling wheel, in order to exclude friction-generated activation of stretch receptors. Each subject was tested with two wheels with the same radius but different widths, 1 mm and 15 mm. On average, the subjects performed better with the wide wheel than with the narrow one for stimulation distances > or = 16 mm. This value also probably exceeds the threshold distance for directional discrimination for the narrow wheel, which indicates that spatial summation improves suprathreshold performance. PMID- 7778408 TI - Thresholds for the perception of pressure, sharpness, and mechanically evoked cutaneous pain: effects of laterality and repeated testing. AB - Twenty-four healthy human subjects provided thresholds for their perception of pressure, sharpness, and pain. Mechanical forces were applied to the dorsal surface of the digits with flat-tipped probes of various sizes. Thresholds (expressed as force) increased with increasing probe size, as previously described. There was no evidence of a laterality difference for any of the thresholds. There was a trend for increasing thresholds with repeated testing, but this trend was not statistically significant for the group as a whole. Examination of individual subjects' thresholds over time revealed that 27% showed significant increases in pain threshold over the 15 days of testing. In contrast, only 6% of subjects showed significant increases in sharpness or pressure thresholds over the same period. Thus, whereas most subjects exhibited stable pain thresholds, approximately one-fourth showed significant increases in pain threshold over time. We conclude that for evaluating regional dysesthesia or hemidysesthesia, a right-left difference in pain thresholds will provide a more sensitive and reliable measure than absolute pain threshold. PMID- 7778409 TI - Activation of the c-fos proto-oncogene in the spinal cord following noxious stimulation of the urinary bladder. AB - Activation of the c-fos proto-oncogene following mechanical or chemical noxious stimulation of the urinary bladder was studied at T12-L2 and L5-S1, the spinal cord segments of projection of the hypogastric nerve (HGN) and pelvic nerve (PN) fibers, respectively. In intact adult rats, c-fos expression was found at T12-L2 only in lamina I. At L5-S1, Fos cells occurred in lamina I, the intermediolateral gray matter (ILG), and the dorsal commissure (DCM). These two areas contained the highest number of immunoreactive cells. Although more Fos cells were induced by mechanical than by chemical stimulation, the distribution of the reactive neurons was similar after both types of stimuli. In adult rats that had been treated neonatally with capsaicin, there was a marked fall in c-fos activation by mechanical or chemical noxious stimuli in all immunoreactive areas. The loss of Fos cells was more pronounced in ILG and DCM at L5-S1 (95%) than in lamina I at the two spinal domains (70%). The confinement of c-fos activation to lamina I at T12-L2, the spinal cord domain of the HGN, suggests that the input carried from the bladder by this nerve is preferentially used for pain perception. The same function is expected for noxious input reaching lamina I at L5-S1, the spinal cord territory of termination of the PN. However, the striking number of Fos cells in ILG and DCM supports the important role played by this nerve in the control of the micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778410 TI - Response of monkey glabrous skin mechanoreceptors to random-noise sequences: I. Temporal response characteristics. AB - The response of slowly adapting (SA, Merkel cell), rapidly adapting (RA, Meissner), and Pacinian corpuscle (PC) mechanoreceptors in monkey glabrous skin were recorded while being activated with a vibrotactile indenting stimulus. For one set of experiments, the stimulator was driven by an 800-point (400-msec) pseudorandom-noise (PRN) sequence, repeated 40 times. For a second set of experiments, a non-repeating-noise (NRN) sequence was used. SA impulse patterns generated with the PRN sequence were highly regular and similar for all afferents tested. RA and PC response patterns were more varied, but exhibited basic intraclass similarities. SA and RA PRN stimulus impulse patterns were often nearly indistinguishable at low to medium discharge rates. At higher discharge rates, RA and SA discharge patterns differed, primarily because of the unambiguous suprathreshold velocity sensitivity and shorter recovery periods of RA afferents. PC impulse patterns were substantially different from SA and RA patterns, being clearly dependent on the stimulus velocity at all stimulus intensities. Input-output correlation analysis, coupled with PRN stimulus response analysis, provided a basis for hypothesizing the basic dynamic encoder function of each type of mechanoreceptor. PMID- 7778411 TI - The effects of aging on information-processing channels in the sense of touch: I. Absolute sensitivity. AB - Thresholds for detecting vibrotactile signals of variable frequency applied to the thenar eminence of the hand by small and large contactors were measured in subjects ranging in age from 10 to 89 years. Thresholds were found to increase as a function of age, but the rate of increase was greater after than before the age of 65 years. The rate of loss of vibrotactile sensitivity was substantially greater in the P channel (mediated by Pacinian corpuscles) than in the NP I channel (mediated by rapidly adapting fibers), the NP II channel (mediated by slowly adapting type II fibers), or the NP III channel (mediated by slowly adapting type I fibers). Women were frequently found to have greater sensitivity than men. PMID- 7778412 TI - The effects of aging on information-processing channels in the sense of touch: II. Temporal summation in the P channel. AB - Thresholds for detecting 250-Hz vibrotactile signals of variable duration applied to the thenar eminence of the hand were measured in 16 subjects ranging in age from 19 to 81 years. Detection thresholds were higher in older than in younger subjects. Correlation coefficients for the relation between threshold and age ranged from 0.94 to 0.96, depending on signal duration. In addition, the amount of temporal summation was negatively correlated with age. Both the elevated detection thresholds and the reduced amount of temporal summation in elderly subjects may be partially due to the decrease in the number of Pacinian corpuscles in the hand that occurs with aging. Another factor that could be responsible for reduced temporal summation in older as compared to younger subjects is impairment of the temporal integrator. PMID- 7778413 TI - Classification systems for health information: nursing components. Part 1: Client status. PMID- 7778414 TI - Betadine cleansing: central venous catheter sites. Interview by Eve Henderson. PMID- 7778415 TI - Nursing research support services: Foothills Hospital. PMID- 7778416 TI - Nurses' perceptions of informed consent. PMID- 7778417 TI - To incorporate or not? PMID- 7778418 TI - Community health nursing ready to meet the challenges of health reform. PMID- 7778420 TI - You called. PMID- 7778419 TI - A rural experience for nursing students. PMID- 7778421 TI - African strategy. How to fight the human immunodeficiency virus. PMID- 7778422 TI - Effects of single and combined application of anti-cancer drugs on cervical adenocarcinoma. I. Antitumor activity in vitro. AB - BACKGROUND: Establishment of effective combination chemotherapy regimen for patients with an adenocarcinoma of the uterine cervix has been long-awaited because there has been no documentation concerning chemosensitivity of this tumor against conventional antitumor agents. METHODS: To search for an effective combination regimen, 15 conventional antitumor drugs were tested for growth inhibitory effects on five different cervical adenocarcinoma cell lines. RESULTS: Etoposide, mitomycin C, adriamycin, epirubicin, and vinblastine, were singularly effective. Effects of combination chemotherapy were also tested using the above five antitumor agents plus interferon-gamma. Etoposide, mitomycin C, and interferon-gamma were the most effective when given in combination. CONCLUSIONS: Combined treatment with the above three drugs seems worthy of consideration for clinical application. PMID- 7778424 TI - Placenta previa, maternal smoking and recurrence risk. AB - In order to assess the risk of placenta previa among women who smoked during pregnancy and to study the recurrence risk of placenta previa, we analyzed data from the Swedish Medical Birth Registry. Among 1,825,998 infants of women delivered in 1973-1990, 5,683 had placenta previa registered. The overall incidence of placenta previa was 0.3%, the incidence in twin deliveries was also 0.3%. The recurrence rate of placenta previa was 2.4%, which is an eightfold increase compared with the rate of a placenta previa among all births. Maternal smoking was studied for births in 1983-1990 and appeared as an independent risk factor for placenta previa. A dose-response between the number of cigarettes smoked during pregnancy and the risk of having a placenta previa was indicated. PMID- 7778423 TI - Hemodynamic, hematological and hemorrheological evaluation of post-term pregnancy. AB - OBJECTIVE: To evaluate the hemorrheological modifications in post-term pregnant women. METHODS: Pregnant women (n = 48) at > 280 days' gestation, were tested on alternate days by nonstress test; ultrasound assessment of amniotic fluid volume, placental grading, hourly measurement of fetal urine production, and maternal fetal Doppler analysis. We further recorded maternal: plasma viscosimetry, red blood cells, hemoglobin, hematocrit, platelet count, mean platelet volume, fibrinogen, antithrombin III, creatinine, uric acid, plasma calcium, hPL, and estriol. We analyzed the last values obtained within 48 hours prior to delivery. RESULTS: The subjects were divided into Group I (40 wks to 40 wks+3 days; n = 16); Group II (40 wks+4 days to 41 wks; n = 16); Group III (> 41 wks; n = 16). The time-averaged maximum velocity of the fetal descending thoracic aorta was lower at Doppler analysis in Group III (29.0 +/- 3.5 cm/s) than in Group I (34.0 +/- 4.3 cm/s; p < 0.05). A decrease of the middle cerebral/umbilical pulsatility index ratio (1.75 in the Group I vs 1.52 in the Group III; p < 0.05) was shown. Furthermore, the incidence of oligohydramnios; Grannum placental grade III; plasma viscosity and coagulation parameters were significantly higher in Group III patients. The plasma viscosity resulted positively correlated with uric acid, and inversely correlated with fibrinogen, antithrombin III and platelet number values. CONCLUSIONS: From the present data we conclude that post-term pregnancy may mimic a mild 'fetal growth restriction'. PMID- 7778425 TI - Symphysis-fundus height: construction of a new Swedish reference curve, based on ultrasonically dated pregnancies. AB - Repeated measurements of the symphysis-fundus (SF) distance is generally regarded as an acceptable screening instrument for antenatal detection of intrauterine growth retardation (IUGR). In the present investigation an SF curve is constructed, based on measurements from 1650 Swedish women with ultrasound dated pregnancies. The SF measurements were included in a cross-sectional stratified manner; only one measurement from each woman was used and the same number of measurements (n = 75) was used for each gestational week from 20 through 41. A regression analysis by a polynomial equation of third degree was applied on the means and standard deviations of the SF measurements in each week respectively to construct a graph of fundal height. This SF curve was compared with the SF curve in common use in Sweden (constructed by Westin); in the new curve the mean measurement was about one cm higher up to 37 gestational weeks, after which time the curves almost coincided. Neither did the mean SF height differ between smokers and non-smokers nor between nulliparous and parous women. The mean SF difference between the heaviest women (> or = 79 kg) and the lightest (> or = 53 kg) was about two cm throughout pregnancy. The validity of the constructed SF curve as a screening instrument for IUGR needs to be investigated in a different study. PMID- 7778426 TI - Umbilical artery Doppler ultrasound predicts low birth weight and fetal death in hypertensive pregnancies. AB - BACKGROUND: Doppler ultrasound is nowadays common in the management of pregnancies complicated with hypertension, as an indirect assessment of fetal well-being. However, the value of abnormal umbilical artery Doppler results in predicting poor fetal outcome in hypertensive pregnancies has been studied in only a small number of patients. We designed a study to investigate the relation between abnormal umbilical artery Doppler velocimetry and fetal outcome in hypertensive pregnancies. DESIGN: A prospective observational study over a 2-year period was performed at the Hospital Clinic, University of Barcelona. Pulsed Doppler examinations of the umbilical artery were performed in one hundred and seventy-two hypertensive pregnant women. The physicians managing the case were not aware of the Doppler results. The incidence of low birth weight and fetal death were considered as the main outcome measures. RESULTS: When low birth weight was used as an end-point, abnormal resistance index showed a high specificity (95.16%), positive predictive value (83.33%), and negative predictive value (86.76%). Sensitivity was 62.5%. The absence of end-diastolic velocity predicted low birth weight in 100% of pregnancies and fetal death in 66.66%. All stillbirths had absence of end-diastolic velocity (sensitivity 100%). CONCLUSION: This study demonstrates that umbilical artery Doppler velocimetry is a useful tool to assess fetal well being in hypertensive pregnancies. PMID- 7778427 TI - Microalbuminuria following gestational diabetes. AB - BACKGROUND: Microalbuminuria (MA) precedes clinical nephropathy in patients with insulin-dependent diabetes mellitus, and is associated with an increased mortality, mostly due to cardiovascular disease in patients with non-insulin dependent diabetes mellitus. Microalbuminuria is rarely detected in patients with diabetes of less than five years' duration. Our study was designed to determine whether MA and its sequelae also appear 5-8 years after pregnancy complicated by gestational diabetes mellitus (GDM). METHODS: We examined the presence of MA in 72 women who had not conceived since a previous GDM-pregnancy 5-8 years ago and compared them to a control group of 35 women who had no GDM history, and who were matched for age, parity and time since last pregnancy. Microalbuminuria was determined in all subjects using an overnight 8 hours urine collection. Mann Whitney rank-sum test was used to compare data between the study and the control groups. Student's t test was used to compare data within the study group. RESULTS: Median value of the urinary albumin excretion rate (AER) in the study group was significantly higher than median value of urinary AER of the control group (p < 0.0001), but only 30.5% of the subjects of the study group were found to be microalbuminuria-positive, defined as urinary AER value of more than 21 mg/24 h. No correlation between MA and blood pressure, fasting blood glucose, serum creatinine, blood urea nitrogen and parity was found. CONCLUSIONS: MA was found to be more frequent after GDM and no predisposing factors for its appearance were elucidated. Hence, we suggest that it may well be a sign of early renal disease and that long-term follow-up of all GDM patients for MA and other markers of renal disease is strongly indicated. PMID- 7778428 TI - Laparoscopic surgical procedures for early ovarian cancer. AB - Early stage la ovarian cancer diagnosed at the time of laparoscopic procedure was managed by laparoscopy accordingly. The procedures included oophorectomy, contralateral ovarian biopsy, total omentectomy, paraaortic lymphadenectomy and appendectomy. The patient tolerated the procedures smoothly and resumed work in two days. PMID- 7778429 TI - Persistent episiotomy granulation polyps; a polysymptomatic clinical entity. AB - We describe a number of patients with persistent symptoms of vaginal discharge and discomfort, dyspareunia and postcoital bleeding. They presented 2-4 months following delivery with episiotomy. In these patients, the symptoms were associated with localised granulation tissue polyps, on the episiotomy site. Simple ablation resulted in rapid and effective relief of the symptoms. These lesions may be more common in clinical practice than is suggested by the lack of published reports. They should be looked for in women who may suffer from symptoms for several months after delivery. PMID- 7778430 TI - A quality of life perspective on who benefits from estradiol replacement therapy. AB - STUDY OBJECTIVE: To examine who may benefit from estrogen replacement therapy from a quality of life (QoL) perspective, taking both disease-specific and general aspects at baseline into account. DESIGN: A double-blind multi-center randomized placebo-controlled prospective study. The subjects were randomized to receive either transdermal estradiol or placebo for 12 weeks. QoL measures were disease-specific and generic. LOCATION: University hospital, teaching hospital and private practice. MATERIAL: Post-menopausal volunteering Swedish women (n = 223) with mild to severe climacteric symptoms, as clinically evaluated by the Kupperman's Index. RESULTS: All QoL assessments showed highly significant improvement in the estradiol group in comparison with the placebo group. The women receiving placebo treatment also improved, but their improvement reached a peak at six weeks of treatment and then declined. In the estradiol group the improvement continued throughout the 12 weeks. After 12 weeks of treatment the change in the placebo-treated group was smaller on the disease-specific scales than on the generic scales and the Kupperman's Index. A high correlation was seen between the baseline score for a certain QoL assessment and the change in this score during treatment. The most striking result was that the mean change in QoL for the two groups was statistically significant for almost any pre-treatment QoL status. CONCLUSIONS: Women with slightly, moderately or severely diminished QoL status would benefit from estrogen treatment during the climacteric period. A similar tendency was seen in women with mild symptoms at baseline. PMID- 7778432 TI - Computerized colposcopy and conservative management of cervical intraepithelial neoplasia in pregnancy. AB - BACKGROUND: Computerized colposcopy is the noninvasive digital processing of colposcopic images acquired using a charge-coupled device camera. The purpose of this study was to evaluate the clinical applications of computerized colposcopy, and to record the colposcopic changes associated with progression or regression of cervical intraepithelial neoplasia in pregnancy. METHODS: Forty-one pregnant patients, with abnormal Papanicolaou smears and a fully visualized squamo columnar junction, were serially monitored throughout their pregnancies using computerized colposcopy. All patients had baseline computer-assisted measurements of their cervical lesions and a repeat measurement at monthly intervals and at 3 months postpartum. RESULTS: During the period of gestation, 17.1% of lesions increased in size, 21.9% remained unchanged, 41.5% decreased in size and 19.5% disappeared completely. In patients with an increase in lesion size, a colposcopically directed punch biopsy was performed which revealed CIN III but no microinvasion. Cervical biopsy during pregnancy was unnecessary in 82.9% of cases. CONCLUSION: The ability to sequentially monitor and quantify colposcopically visualized lesions, using computerized colposcopy, provides a noninvasive objective mode to evaluate progression, stability, or regression of CIN lesions during pregnancy. PMID- 7778431 TI - Management of uterine perforations in connection with legal abortions. AB - The incidence of uterine perforation while performing legal abortions was evaluated in the Stockholm area. Among 84,850 legal abortions performed during 1982-1992 there were 145 cases of uterine perforation, 0.17%. In about half of these cases an immediate exploration of the abdomen was decided upon and in 18 patients there were significant bleeding and/or lacerations to organs situated in the pelvis. No case of intestinal perforation was encountered. It is likely that many of these injuries would have healed just as well unattended. Based on this study, the authors advocate a conservative approach in dealing with uterine perforation in connection with vacuum aspiration for legal abortion. PMID- 7778433 TI - Therapeutic and prognostic considerations in primary carcinoma of the vagina. AB - We analyzed 46 patients with primary carcinoma of the vagina treated between 1969 and 1990. Median age of the patients was 67 years (range 33-89 years). Most (52%) of them were obese and 35% were nulliparous. Four (9%) had suffered from other gynecologic carcinoma and had been operated six to 23 years before the current carcinoma. Forty (87%) patients had squamous cell carcinoma. Stage 0 (carcinoma in situ) was found in three (7%) cases and stage I-IV in 21 (54%), 10 (22%), four (9%) and eight (17%) cases, respectively. Most (81%) of the patients were treated with radiotherapy (alone or in combination with other treatments): combination of brachytherapy and external radiotherapy were used in 45% of the cases. Surgery was used in all stage 0 cases and in 52% of stage I cases. Recurrence of the disease was found in 20 (43%) cases during the follow-up of 10 years. Most often (40%) site of the recurrence was the vagina. Both 5- and 10-year survival were 38%. Stage and extent of the tumor were independent prognostic factors in stepwise multivariate analysis. PMID- 7778435 TI - Pregnancy complicated by malignant melanoma. PMID- 7778434 TI - Malignant germ cell tumors of the ovary: Hacettepe hospital experience. AB - BACKGROUND: To determine the most important prognostic factors in patients with malignant germ cell tumors of the ovary. METHODS: Age, histologic type, tumor size, stage, treatment mode, type of surgery of 67 patients with malignant germ cell tumors managed consecutively were evaluated retrospectively using multivariate analysis. RESULTS: The overall survival rate was 60.6%. This figure was 78.5% for dysgerminoma, 53.3% for immature teratoma, 12.0% for endodermal sinus tumor, 33.3% for mixed germ cell tumor and 100.0% for others. The patients with endodermal sinus tumor had significantly poorer survival than other groups. Among the factors analyzed for survival histologic type was found to be the most significant predictor for survival. CONCLUSIONS: Finding of histologic type as the strongest independent risk factor may be evaluated in correlation with the literature that these tumors have historically been investigated as dysgerminomatous and nondysgerminomatous tumors. Furthermore, endodermal sinus tumors had long been known for poor survival. Based on this data, despite advent of staging and effective chemotherapy, prognosis still is basically related to histologic type and histology of tumor should be taken into account while comparing results. PMID- 7778436 TI - Postpartum systemic capillary leak syndrome: a possible etiology. PMID- 7778437 TI - Twin transfusion syndrome associated with placental venous calcification. PMID- 7778438 TI - Dorsoposterior fetal position near term--a sonographic finding worth noting? PMID- 7778439 TI - Flow characteristics in infants with hypoplastic left heart syndrome: an echocardiographic study. AB - From July 1992 to January 1993, a total of 5 cases of hypoplastic left heart syndrome were diagnosed by echocardiograms and confirmed by available angiographic, surgical or autopsy results. The flow dynamics disclosed by spectrum display in the aortic root and patent ductus arteriosus (PDA), in systole, were: (1) antegrade in the ascending aorta and descending aorta (below PDA), and retrograde in the transverse aorta, and (2) right-to-left shunt in the PDA. While in diastole, there were (1) antegrade in the transverse aorta, and retrograde in the ascending aorta and descending aorta (below PDA), and (2) left to-right shunt in the PDA. No ventriculocoronary fistulas were identified. With both the characteristic flow pattern and the extremely narrow diameters of the ascending aorta in hypoplastic left heart syndrome, we can differentiate it from those heart diseases associated with secondary hypoplastic left heart due to total anomalous pulmonary venous connection or congenital pulmonary venous stenosis. Both help us understand better the hemodynamics and pathophysiology of hypoplastic left heart syndrome in these patients. PMID- 7778440 TI - Sinusitis and bronchial asthma in children. AB - Sinus disease has been assumed to exist in children with respiratory tract allergies. We consecutively evaluated 375 patients (245 male, 130 female) with childhood onset asthma, between 5 and 15 years of age (mean 7.8 years of age). Abnormal Waters radiographs were found in 205 patients (54.7%) which included mucosal wall thickening greater than 6 mm (67.3%), complete opacification (22.9%) and air-fluid levels (9.8%). The level of immunoglobulin (Ig) E was found to be much higher in non-sinusitis asthmatic children than in asthmatic children with sinusitis (1207 IU/mL vs. 644 IU/mL). The IgG, IgA, IgM and erythrocyte sedimentation rate (ESR) values were not significantly different in the two groups. All patients were treated with antibiotics for 3 to 6 weeks. Five patients required surgical intervention after antibiotic treatment had little success. Streptococcus viridans was isolated from 4 patients following surgical aspirates and Peptostreptococcus anaerobius was isolated in only one patient. In conclusion, sinusitis in children may be an aggravating factor for chronic reactive lower airway disease. Optimal treatment may decrease the need of asthmatic medication. PMID- 7778441 TI - Non-hyperventilation respiratory therapy of persistent pulmonary hypertension of the newborn. AB - Persistent pulmonary hypertension of the newborn (PPHN) is one of the most challenging situations in the neonatal intensive care nursery and it is associated with a high mortality rate. Hyperventilation therapy has been recommended as the primary ventilator management during recent decades. The associations of pulmonary barotrauma, chronic lung disease and hearing impairment raised the questions of significant pulmonary and neurological complications with this therapeutic modality. From July 1990 to April 1993, 14 cases of neonatal persistent pulmonary hypertension were treated with nonhyperventilation respiratory therapy at the Chang Gung Memorial Hospital. The goals of this therapy were to attain a pH level between 7.40 and 7.50, a PaO2 level between 60 and 90 mmHg and a PaCO2 level between 30 and 50 mmHg. High peak inflating pressure (> 35 cmH2O) and high ventilator rates (> 60/min) were avoided. The average duration on a ventilator was 6.8 +/- 2.9 days. Four patients had pulmonary barotrauma (29%); three of which were pulmonary interstitial emphysema and one pneumothorax. Three patients died (21%). Only one patient had neurological sequelae. No one had developed chronic lung disease. The non hyperventilation approach for PPHN may be considered as an alternative ventilator management before starting a more aggressive hyperventilation therapy. PMID- 7778443 TI - The VATER association: analysis of forty six cases without karyotyping. AB - Forty-six patients with two or more features of the VATER association admitted to the Mackay Memorial Hospital from May, 1983 to Mar, 1992 were retrospectively enrolled in this study. We compared the incidence of major features with that reported in the literature. Imperforate anus, congenital heart disease, and renal anomalies were the three most common major features in our study. Thirteen patients died. Heart failure was the major cause of mortality. We noted many patients associated minor features, and among them there was a relatively high ratio of cleft lip, cleft palate, and hypospadius. The overall outcome and development were good among the survivals. We suggest that children who have any congenital anomaly included in the VATER association should get a careful examination and evaluation of their heart, genitourinary tract, limbs and vertebrae. Early correction if possible is indicated in such patients. PMID- 7778442 TI - Characterization of Albright hereditary osteodystrophy and related disorders. AB - Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder with characteristic skeletal and developmental defects and reduced expression or activity of the alpha chain of the G protein that stimulates adenylyl cyclase (Gs alpha). Most patients with AHO exhibit target tissue resistance to multiple hormones whose actions are mediated by cyclic AMP (cAMP) as a second messenger, such as the parathyroid hormone (PTH). This form of the disorder is known as pseudohypoparathyroidism (PHP) type Ia. Patients with PHP type Ia usually have relatives with AHO who do not exhibit hormone resistance despite having the same defect in Gs alpha. This variant, yet unexplained, is known as pseudopseudohypoparathyroidism (PPHP). PHP type Ib is manifested by a limited hormone resistance to PTH and is believed to be caused by defects in the PTH receptor. Patients with PHP type Ic have normal Gs alpha activity and show morphologic defects similar to those in AHO as well as resistance to multiple hormones. PHP type II, a much rarer disease, is probably caused by vitamin D deficiency. PMID- 7778444 TI - Self-management and attributes of juveniles with insulin-dependent diabetes mellitus. AB - The purpose of this study was to investigate the self-reported self-management of juveniles with IDDM and the factors influencing self-management. Sixty-eight subjects, ranging from the fourth grade of primary school to the third year of junior high school, were recruited from the enrollment list of the Taipei IDDM Registry and from the list of the Kang-Tai IDDM Association. Results illustrated that patient's age, educational level, knowledge about IDDM, self-concept, and family rearing behaviors had significant associations with some aspects of self management. Intensive health education or counselling for patients and their parents is highly recommended in order to improve their knowledge, self management practice and psychosocial adjustment. PMID- 7778446 TI - Chylous ascites: report of one case. AB - Chylous ascites is rare if found in the pediatric age group, and is usually of unknown etiology or comes from congenital anomalies of the lymphatic system. A 3.2 kg male newborn was born at 36-week gestation by Cesarean section prompted by fetal distress. Distended abdomen was noted after birth and abdominal ultrasound revealed significant ascites. Repeated paracenteses were done to relieve the respiratory distress, and a milky ascitic fluid with specific gravity of 1.031, WBC 1.32 x 10(4)/mm3 (lymphocytes predominant), and triglycerides 812 mg/dl was noted at the third tapping after feeding with normal infant formula. The lipoprotein electrophoresis of the ascites showed great increase in proportion of chylomicron to 19.05%. Pregestimil was given, and the ascites gradually subsided. The patient was discharged on the 13th day after birth. His growth was normal at one-month follow up without recurrence of ascites. PMID- 7778445 TI - The study of pollen and Der p mite-specific IgE antibodies in children with allergic rhinitis. AB - The role of pollens and house dust mites in perennial chronic rhinitis has been investigated for the Taipei area. Fifty-four serum specimens were collected from children with chronic rhinitis. EIA kits (Phadezyme RAST) were used to detect specific IgE antibody of nine allergens, including house dust mite (Der p) and eight common pollens. The children were divided into allergic (AR) and nonallergic (NAR) groups, based on the results of skin tests, inhalant allergen specific IgE screen (Phadiatop), physical examination, past history and family history. The results showed: (1) 41 (76%) patients were defined as allergic rhinitis; (2) Der p specific IgE was detected in 41 (100%) AR patients and 7 (54%) NAR patients (P < 0.005), a strong positive reaction (> 2+) in 83% AR and none NAR patients (P < 0.005); (3) one, or more than one, pollen-specific IgE were found in 13 (32%) AR and 4 (31%) NAR patients. No strong positive reaction was detected in either group. THE CONCLUSION: (1) three-fourths of the children with chronic rhinitis are allergic by nature; (2) house dust mite is the major allergen of allergic rhinitis; (3) in the Taipei area, pollen does not play an important role for children with allergic rhinitis. PMID- 7778447 TI - Common atrium with Ebstein's anomaly in a neonate with Ellis-van Creveld syndrome. AB - A female newborn with characteristic multiple anomalies of Ellis-van Creveld syndrome is reported. Common atrium with Ebstein's malformation of the tricuspid valve was diagnosed by serial echocardiographic examinations. Such a combination of cardiac anomalies have not previously been reported in this syndrome. PMID- 7778448 TI - Experience of intravenous immunoglobulin and acyclovir in neonates at risk for severe varicella infection--report of five cases. AB - Five cases of at-risk neonates for severe varicella infection were reported. Intravenous immunoglobulin (IVIG) was given soon after birth in different ways to four of them (Case 1 received 400 mg/kg/day for the first three days of life; Case 2 received a single dose of 200 mg/kg on day 2, and another dose of 160 mg/kg on day 7; Cases 3 and 4 received 400 mg/kg on day 2). All five patients were given acyclovir therapy, 40 to 45 mg/kg/day for five to nine days. (Case 1 for prophylaxis, Cases 2, 3, 4, 5 for treatment). Case 2, 3, 4, 5 developed vesicular rash, mild to moderate in degree, with rapid resolution without any constitutional symptoms. Case 1, who received both IVIG and acyclovir for prophylaxis, had no vesicle occurrence. IVIG, in combination with acyclovir, is a safe and probably effective regimen for preventing severe varicella in at-risk neonates. A multi-centered, collaborative study is mandatory to study the efficacy of prophylactic acyclovir with IVIG in these neonates. PMID- 7778449 TI - Intestinal volvulus caused by a persistent omphalomesenteric band: report of one case. AB - Persistent omphalomesenteric band is a rare cause of volvulus or intestinal obstruction. A 7-month-old male infant was brought to this Emergency Room after having shown poor appetite for three days, frequent bilious vomiting, and fever for half a day. Physical examination revealed the infant was dehydrated and had slight abdominal distension as well as hypoactive bowel sounds with a tender, ill defined mass over right lower quadrant. Radiography and sonography were consistent with distal small bowel obstruction. Emergent laparotomy was done and a fibrous band found extending from the anti-mesenteric border of the ileum to the posterior wall of the umbilicus. Small bowel volvulus had occurred around the band and dilated small bowel was noted. An understanding of the embryologic development of these structures and their normal disappearance may assist pediatricians and surgeons to make the correct diagnosis and select the right pathoanatomic approach in surgery. PMID- 7778451 TI - Characterization of sports by the VO2 dynamics of athletes in response to sinusoidal work load. AB - The purpose of this study was to evaluate the specificity of maximal oxygen uptake (VO2max) and the dynamic response of oxygen uptake (VO2) to sinusoidal work load in distance runners and in American-football players. Sinusoidal work load during ergometer cycling was carried from 30 W to 60% to VO2max (60% VO2max) for a 2 min period. VO2 was measured by the breath-by-breath method. The subjects were 10 distance runners (DRs), 10 American-football players (AFPs), and 11 untrained men (UTM). Mean VO2max was 64.4 mL kg-1 min-1 in the DRs, 53.1 mL kg-1 min-1 in the AFPs and 47.3 mL kg-1 min-1 in the UTM. The fundamental amplitudes of the VO2 response, normalized by dividing by steady state VO2 at 60% VO2max, were similar in the AFPs (20.3%) and the UTM (19.5%), and both were significantly less than in the DRs (25.5%). Phase shift to work load expressed in degrees was similar in the AFPs (87.7 degrees) and UTM (88.0 degrees), but significantly greater than in the DRs (80.4 degrees). HR dynamics in all three groups were similar to a dynamic VO2 response. These findings suggest that development of the dynamic VO2 response and higher VO2max is achieved in the DRs. They also suggest that despite the higher VO2max in the AFPs there is no improvement in the dynamic VO2 response. The results of the present study demonstrate that athletes participating in different sports have characteristic dynamic VO2 responses during cycling exercise. PMID- 7778450 TI - Thyroid hormone regulation of myosin heavy chain isoform composition in young and old rats, with special reference to IIX myosin. AB - The effects of 4 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3) treatment on the myosin heavy chain (MHC) composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscles from young (3 6 months) and old (20-24 months) male albino rats. Four MHC isoforms were separated on silver-stained 6% sodium dodecyl sulphate polyacrylamide gel electrophoresis. According to immunoblotting experiments with specific MHC monoclonal antibodies, the four MHCs corresponded to types I, IIB, IIX and IIA. In the soleus, the type I MHC content was higher in the old than in the young animals, and the type IIA content lower. Type IIX myosin was observed in some young control soleus, but not in old ones. After T3 treatment, the content of type I MHC decreased substantially in both young and old animals and that of type IIA increased. After T3 treatment, type IIX myosin was observed in both young and old animals, with a slightly higher IIX myosin content in old age, but the age related difference in the contents of types I and IIA was diminished. In EDL, the type IIX MHC content was significantly higher in the old animals, at the expense of a lower content of type IIB MHC. MHC composition was not affected significantly by T3 treatment in EDL, either in young or old animals. In conclusion, an age-related motor unit transformation is observed in both the slow twitch soleus and the fast-twitch EDL and the capacity for MHC isoform switching in response to T3 treatment is not impaired in old age. PMID- 7778452 TI - Pitfalls in the interpretation of spectral analysis of the heart rate variability during exercise in humans. AB - The recent use of spectral analysis of the R-R interval variability to assess the autonomic drive during exercise has produced inconsistent results. The purpose of this study was to assess whether the spectral components of the R-R interval variability reflect different mechanisms at rest and during exercise. Autoregressive spectral analysis of the electrocardiographic and breathing signals was performed in 11 healthy young men at rest and during incremental cycle ergometry. The amplitude of respiratory sinus arrhythmia, i.e. the absolute power of the high frequency spectral component, fell at the onset of exercise, consistent with a reduction in cardiac vagal activity. Conversely, the normalized power of the high frequency component, (i.e. the percentage of R-R interval variance due to the respiratory sinus arrhythmia) increased with increasing work rates. The low frequency spectral component of the R-R interval variability, which when expressed in normalized units is believed to reflect cardiac sympathetic activity, was no longer detectable in severe exercise when the adrenergic drive is known to be elevated. In conclusion, autoregressive spectral analysis of the R-R interval variability does not adequately reflect the autonomic changes that occur during incremental exercise. In particular, the evidence indicates that as the cardiac vagal tone falls with increasing levels of exercise, a greater percentage of the residual power of the high frequency component may be due to non-neural mechanisms. PMID- 7778453 TI - Excitation and contraction in atrial and ventricular myocardium of the guinea pig. AB - Several parameters of excitation-contraction coupling were compared in two types of muscle, using thin strips from the left atria and papillary muscles from the right ventricles of guinea-pigs. (1) The duration of the action potential and twitch is much longer in ventricular than in atrial muscle. (2) Mechanical restitution can usually be described by a monoexponential function in ventricular and biexponential function in atrial muscle. (3) Post-extrasystolic potentiation, when related to the steady state force, is greater in ventricular muscle. (4) When priming with paired-pulse stimulation, mechanical restitution can be studied after the short interval and after the long interval. In atrial muscle, mechanical restitution is very similar after the short and long intervals but in ventricular muscle they are different in size. (5) Ryanodine (10(-6) M) can decrease the steady state force to about 10% of control in atrial but only to about 35% in ventricular muscle. Ryanodine (10(-8) M) causes the slow phase of restitution in atrial muscle to disappear but in ventricular muscle only increases the rate of mechanical restitution. (6) Ca-antagonists (Cd2+ 0.2 mM) can decrease the steady state force to zero in atrial and ventricular muscle. Ca antagonists, in low concentrations (Cd2+ 0.01 mM), mainly affected the fast phase of mechanical restitution. (7) The recirculation fraction of calcium was about 0.64 in atrial and 0.27 in ventricular muscle. The findings are discussed in the light of known ultrastructural differences between atrial and ventricular myocardium. PMID- 7778454 TI - Myocardial inositoltrisphosphate is depressed by dibutyryl cAMP. An experimental study in the isolated working rat heart. AB - A possible interrelation between IP3 and cAMP was studied in rat myocardium through circumvention of the receptor mediated stimulatory step of adenylyl cyclase by the administration of dibutyryl cAMP (db-cAMP). Changes in IP3 and cyclic nucleotide contents were correlated to changes in contractility after 40 min of beta- and alpha-adrenergic stimulation. Rat hearts (n = 23) were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were allocated to perfusion as control (n = 6); or with phenylephrine (10(-6) mol L-1, n = 6); (-)-isoproterenol (10(-6) mol L-1, n = 6); db-cAMP (2 x 10(-4) mol L-1, n = 5). All hearts were freeze-clamped after 40 min of perfusion. Phenylephrine produced a slow increase in maxdP/dt reaching a maximal value after 10 min (P < 0.05); thereafter it decreased, reaching the control level at 30 min. Isoproterenol perfusion resulted in an early (20 s) increase in maxdP/dt (P < 0.05). Over the next 10s maxdP/dt decreased markedly reaching an inflection point at 30 s. Thereafter only a slow increase during the rest of the perfusion was seen. Dibutyryl cAMP increased maxdP/dt slowly during the whole perfusion period reaching maximum after 40 min. Cyclic-AMP was increased by 21% after 40 min of phenylephrine perfusion while the corresponding increases by isoproterenol and db-cAMP were 131 and 105%, respectively (P < 0.05). Phenylephrine increased IP3 content to the same extent as isoproterenol perfusion (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778455 TI - Carbachol-induced increase in inositol trisphosphate (IP3) content is attenuated by adrenergic stimulation in the isolated working rat heart. AB - The interrelated responses of concomitant adrenergic and muscarinic receptor stimulation on second messengers and mechanical activity in the isolated perfused working rat heart were studied. The hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus. The hearts were perfused with noradrenaline (10(-6) mol L-1, n = 20), with carbachol (3 x 10(-7) mol L-1, n = 11) or with noradrenaline plus carbachol (n = 20) in the above-mentioned concentrations. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and noradrenaline plus carbachol and at 20 s and 40 min after addition of carbachol. Five hearts were freeze-clamped directly after preperfusion and another five hearts after 40 min of perfusion and used as controls. Myocardial cAMP increased at 20 s and 40 min after noradrenaline perfusion. In contrast to this cAMP was unchanged at 20 s and decreased at 40 min after perfusion with noradrenaline plus carbachol. IP3 content increased after 20 s of carbachol- and after 40 min of noradrenaline perfusion (P < 0.05). However, noradrenaline plus carbachol did not induced any significant increase in IP3 content after 20 s and 30 s, but after 40 min a decrease below basal level was found (P < 0.05). Noradrenaline stimulation attenuated muscarinic agonist induced IP3 formation. A reciprocity existed in that noradrenaline induced IP3 formation was attenuated by carbachol. No direct relationship was observed between the IP3 response and contractility, also valid for cAMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778456 TI - Intravenous lipid infusion results in myocardial lipid droplet accumulation combined with reduced myocardial performance in heparinized rabbits. AB - The question addressed in this study was whether a relation between myocardial lipid droplet accumulation and depressed myocardial function existed following intralipid infusion for 45 min in open chest, anaesthetized rabbits. One group of rabbits (n = 8) received intralipid infusion whereas a control group (n = 8) received sodium chloride. Local myocardial performance was obtained by sonomicrometry and the fractional volume of myocardial lipid droplets was measured by morphometric methods. The fractional volume of lipid droplets was 0.667 +/- 0.116% in the intralipid group compared with 0.318 +/- 0.080% in the control group (P < 0.03). Cardiac output and stroke volume fell 26% (P < 0.0001) and 34% (P < 0.0001), respectively, as a result of intralipid infusion. However, myocardial blood flow obtained by radiolabelled microspheres remained unchanged. Local myocardial function was reduced for both segments after intralipid infusion; maximal systolic shortening was reduced from 15.63 +/- 1.45 to 12.07 +/ 1.55% (P < 0.002) in the circumferential segment and from 9.46 +/- 1.17 to 7.40 +/- 0.53% (P < 0.05) in the longitudinal segment. The end-diastolic length of the circumferential segment was reduced by 3% (P < 0.05) after intralipid infusion. The reduced end-diastolic length of circumferential segments together with unchanged left ventricular end-diastolic pressure might indicate reduced left ventricular end-diastolic compliance. We conclude that acute intralipid infusion in rabbits results in myocardial lipid droplet accumulation and depressed local myocardial function. PMID- 7778457 TI - Renal sodium excretion after oral or intravenous sodium loading in sodium deprived normotensive and spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY. PMID- 7778458 TI - The effects of hypothermia on renal function and haemodynamics in the rat. AB - The effects of 1-2 h of hypothermia at 28 degrees C and rewarming on renal function were investigated in anaesthetized rats, using conventional clearance methods and the micropuncture technique. Renal blood flow (RBF) decreased from 7.3 +/- 0.51 mL min-1 at 37.5 degrees C (control) to 4.0 +/- 0.47 at 28 degrees C, with almost complete restoration to 6.9 +/- 0.59 mL min-1 after rewarming. Systemic blood pressure remained essentially unaltered. The RBF reduction seen during hypothermia was due to a 75% increase in vascular resistance, mainly attributable to constriction of the afferent arteriole and increased blood viscosity. This was accompanied by a decline in glomerular capillary pressure from 56.7 +/- 0.6 to 46.4 +/- 1.3 mmHg, overshooting to 59.0 +/- 0.7 mmHg. The glomerular filtration rate (GFR) decreased from 1.1 +/- 0.08 to 0.6 +/- 0.04 mL min-1, returning to 1.0 +/- 0.07 after rewarming, a pattern also observed for single nephron GFR. This resulted from a decrease in net driving force for glomerular filtration, whereas the filtration coefficient was not affected. Both proximal and distal tubular fluid flow decreased, but fractional reabsorption remained unchanged. In contrast, urine flow increased from 1.8 +/- 0.16 to 5.7 +/ 1.08 microL min-1, returning to 2.1 +/- 0.18, the increase during hypothermia mainly resulting from a disproportionately reduced fluid reabsorption beyond the mid-distal tubule. PMID- 7778459 TI - Fat content affects heat capacity: a study in mice. AB - The specific heat capacity of the human body is a widely used number in calculations related to studies in energy metabolism and temperature regulation. A value of 3.47 kJ kg-1 K-1 has been used during the last century, but there have been no direct studies on the dependence of this value on the body fat content. We present here results of measurements of the specific heat capacity of lean and obese mice. The mice were killed and heated to 40.6 degrees C, transferred to a calorimeter and the specific heat capacity was determined from body mass of the mice and temperature rise of water in the calorimeter. We measured the fat fraction of body mass (mf), fat free body mass and water content of the mice and found a marked dependency of the specific heat capacity (Cp) on body fat. In obese mice (fat content 52.76% body wt) the heat capacity was 2.65 kJ kg-1 K-1 and in lean mice (fat content 7.55% body wt) the heat capacity was 3.66 kJ kg-1 K 1. PMID- 7778461 TI - Haem oxygenase activity in blood vessel homogenates as measured by carbon monoxide production. PMID- 7778460 TI - Sympathetic regulation of fructose secretion in the seminal vesicle of the guinea pig. AB - Fructose secretion of everted guinea-pig seminal vesicles was studied in vitro. Carbachol produced dose dependent increase in fructose secretion. The effect was blocked by scopolamine but not by hexamethonium, mecamylamine, tetrodotoxin or previous denervation. High concentrations of acetylcholine also increased fructose secretion. This response was not augmented by physostigmine. Methoxamine reduced secretion. Methoxamine, terbutaline, clonidine and vasoactive intestinal peptide counteracted carbachol. Field stimulation produced increased secretion that was not blocked by autonomic drugs, tetrodotoxin or previous denervation. Stimulation of the hypogastric nerve produced frequency dependent increase in fructose secretion. The effect was blocked by tetrodotoxin and scopolamine but not enhanced by physostigmine. If the hypogastric nerve was stimulated close to the seminal vesicle the response was unaffected by hexamethonium but proximal stimulation was blocked. After chronic proximal denervation of the hypogastric nerve, stimulation close to the seminal vesicle produced enhanced response. Destruction of the peripheral ganglia at the base of the seminal vesicle abolished the response. Sections showed that most secretory nerves enter the organ at its base. Phentolamine or yohimbine but not prazosine or propranolol or guanethidine enhanced the secretory response to distal hypogastric nerve stimulation. Tyramine counteracted the response but after reserpinization it was enhanced by tyramine. It is concluded that the secretory cells of the guinea-pig seminal vesicle have a sympathetic secretomotor innervation by short cholinergic neurones with a preganglionic supply via the hypogastric nerve. Inhibitory alpha 1 and beta 2-adrenoreceptors are present on the cells but neurogenic adrenergic inhibition of the secretion is essentially prejunctional and due to activation of inhibitory alpha 2-receptors on the secretomotor nerves. PMID- 7778463 TI - The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. PMID- 7778462 TI - Insulinotropic action of truncated glucagon-like peptide-1 in mice. PMID- 7778464 TI - Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects. AB - Five male endurance-trained subjects performed exhaustive exercise on a cycle ergometer at a work rate corresponding to 75% of their VO2max after reduction of their muscle glycogen stores. During exercise the subjects were given in random order a 6% carbohydrate solution continuing 7 g L-1 of branched-chain amino acids (BCAA), a 6% CHO solution and flavoured water. The physical performance was lowered in four of the five subjects when they were given flavoured water during exercise as compared with the two conditions when CHO was supplied. No difference in performance was found when the subjects were given CHO + BCAA or only CHO during exercise. When CHO + BCAA was supplied the plasma and muscle (vastus lateralis) concentrations of BCAA increased during exercise by 120 and 35%, respectively. In the other conditions there was no change or a slight decrease in the plasma concentrations of BCAA, but the muscle concentrations of BCAA were decreased after exercise. The plasma concentration of glutamine over the whole exercise period and 5 min after exercise was higher when CHO + BCAA were supplied during exercise compared with a supply of CHO alone or water. However, exercise caused no change in the muscle concentration of glutamine, whereas that of glutamate decreased in all three conditions. A supply of CHO + BCAA or CHO alone did not affect the exercise-induced increase in the plasma and muscle concentration of aromatic amino acids, indicating that neither BCAA nor CHO influenced the net protein degradation during exercise. PMID- 7778465 TI - Phosphate metabolism of prior eccentrically loaded vastus medialis muscle during exercise in humans. AB - The possible alteration of metabolism of the m. vastus medialis was investigated during exercise after eccentric loading. Twelve male subjects performed stepping exercise for 25-60 min. One week before and 24 h after stepping they performed concentric leg exercise at stepwise increasing intensity, while power output was measured. During this concentric exercise and recovery therefrom, phosphorous metabolites were also measured in the m. vastus medialis with magnetic resonance spectroscopy. Creatine kinase and myoglobin in blood were measured before and 72 h after stepping. T1 and T2 1H-relaxation times for water were calculated from magnetic resonance images collected 72 h after stepping, and used as measures for oedema. The subjects perceived substantial soreness from 24 to 72 h after stepping. The ratio of inorganic phosphate over phosphocreatine at rest increased from 0.12 +/- 0.02 (before) to 0.19 +/- 0.04 (24 h after stepping) (P < 0.05). Creatine kinase activity was slightly elevated 72 h after stepping (71 [49-812] U L-1 [median, range]; P < 0.05) compared with baseline values (58 [26-409] U L-1), whereas myoglobin concentration was not significantly elevated (15 [8-120] micrograms L-1 compared with 8 [8-41] micrograms L-1). In the eccentrically exercised muscles, T1 and T2 values were not or only slightly higher than in the concentrically exercised contralateral muscles. The relation between power and the ratio of inorganic phosphate over phosphocreatine during concentric exercise, and the recovery data for inorganic phosphate, phosphocreatine and pH did not alter after stepping. These data suggest that quadriceps metabolism during concentric exercise and recovery therefrom is not affected by prior eccentric overload, but it cannot be excluded that metabolism will alter during exercise after more strenuous prior eccentric overload. PMID- 7778466 TI - Personality dimensions of opiate addicts. AB - A survey of 80 opiate addicts included in a detoxification program was conducted at the Institute on Addictions in Belgrade. In addition to a dependence diagnosis and mental disorders based on DSM-III-R, we applied a Tridimensional Personality Questionnaire (TPQ) that measures the 3 major personality dimensions: novelty seeking (NS), harm avoidance (HA) and reward dependence (RD). When compared with a control group (a sample of Yugoslav undergraduate students), the opiate addicts demonstrate significantly high NS dimension as well as significant divergences of HA and RD subscales. The surveyed opiate addicts demonstrate a high percentage of personality disorders specifically in cluster B. The personality dimensions of opiate addicts showed certain temperament traits, such as: impulsiveness, shyness with strangers, fear of uncertainty and dependence. NS, HA and RD determined by temperament specifics may be an etiological factor in forming of a personality disorder, an affective disorder as well as of a drug choice. PMID- 7778467 TI - Clinical recovery from panic disorder is associated with evidence of changes in cardiovascular regulation. AB - Cardiovascular measures (spectral derivatives of heart rate variability, the blood pressure response to standing and plasma noradrenaline levels) have been shown to change as clinical recovery follows the treatment of panic disorder patients with either imipramine or cognitive therapy. These findings can be interpreted as evidence of changes in baroreflex modulation, an important feature of the cardiovascular expression of arousal. This offers further evidence of a dysregulation of arousal in this disorder. PMID- 7778468 TI - The predictive value of depression in anorexia nervosa. Results of a seven-year follow-up study. AB - This study investigated the predictive value of depression in patients with adolescent anorexia nervosa. Thirty-four anorectic inpatients were assessed for DSM-III-R comorbid major depression at admission and at 3-year and 7-year follow ups. Two standardized instruments, the Zung Self-rating Depression Scale and the Hamilton Depression Rating Scale, were applied to improve objective rating of depression. The findings suggest that severity of depressive symptoms at admission does not correlate with the severity of depression at follow-up, initial depressive psychopathology is not a valid prognostic indicator for the outcome of the eating disorder and at follow-up there is a highly significant relationship between depression and the outcome of anorexia nervosa. Patients with persisting eating disorder are also very likely to suffer from comorbid depression. PMID- 7778469 TI - Schizophrenics with small P300: a subgroup with a neurodevelopmental disturbance and a high risk for tardive dyskinesia? AB - Schizophrenics with a neurodevelopmental disturbance resulting in micro- and macroanatomical cortical abnormalities are supposed to form a subgroup clinically characterized by low premorbid adjustment, early onset, incomplete remission, poor outcome, male predominance and high risk for tardive dyskinesia. A small amplitude of the event-related P3 (P300) potential could be a marker of this subgroup, because the cortical neurons and their orderly laminar arrangement are crucial for the electrogenesis of P3. In a 2-year follow-up study, auditory evoked P3 was recorded in 89 stabilized schizophrenic outpatients. Patients who developed tardive dyskinesia during the follow-up had smaller P3 than matched controls. Furthermore, a small P3 was associated with low premorbid adjustment, pronounced residual symptoms, low relapse rate, and male predominance. These findings indicate that schizophrenic patients with a reduced P3 have a higher risk of developing tardive dyskinesia and correspond clinically to a schizophrenic subgroup with a supposedly neurodevelopmental disturbance. PMID- 7778471 TI - Definite and undetermined forensic diagnoses of suicide among immigrants in Sweden. AB - A total of 707 cases of violent death (suicide, undetermined mode or accident) occurring in 1990 were investigated at the Department of Forensic Medicine in Stockholm. The catchment area of the Department includes about 1.9 million people. Fourteen percent of the population in the area are immigrants. The largest single immigrant group was the 91,015 Finnish-born inhabitants, who represented 33% of the overall immigrant population. Thirty percent of all undetermined deaths and 20% of the suicides were among people born outside Sweden. A significant overrepresentation of the largest immigrant group (Finnish born) was found in both the definite and undetermined suicide categories. There was also an overall overrepresentation of immigrants among the undetermined cases and a trend towards overrepresentation among definite suicides. Also, there was a significant overall overrepresentation of immigrants in the total cases of undetermined and definite suicide. Some psychosocial factors found predominant among the immigrant sample were social isolation, low social class and poor social network. The findings in this study indicates that immigrant status should be considered as a risk factor for suicide in Sweden. Previous reports on the high suicide rates among immigrants in Australia, Canada, Great Britain and the United States suggest that the overrepresentation of immigrants found in our study could represent a worldwide epidemiological trend related to voluntary and forced migration. Possible hypotheses that could explain this phenomenon are discussed. PMID- 7778470 TI - Blood pressure as a risk factor for depression in elderly people: a prospective study. AB - A total of 1070 men and women aged 65 years and over living in the community in Liverpool were interviewed using the Geriatric Mental State. Diagnoses of depression at case and subcase level were made using the GMS-AGECAT package from an initial interview and at follow-up three years later. Data relating to blood pressure at year 0 was available on 748 subjects. Men not taking anti hypertensives or antidepressants with diastolic blood pressure greater than 85 mmHg were significantly less likely to be subcases than men with low or normal diastolic pressure. People in this group were also significantly less likely to be cases 3 years later. There were no other significant findings. These results do not support an association between low blood pressure and coincidental or future subcase- or case-level depressive illness. PMID- 7778472 TI - Dhat syndrome: is it a distinct clinical entity? A study of illness behaviour characteristics. AB - Dhat syndrome is a culture-bound neurotic disorder seen in the Indian subcontinent. The disorder has recently been included in ICD-10. In the present study, illness behaviour of 50 dhat syndrome patients was studied using a Hindi version of Illness Behaviour Questionnaire (IBQ) and was compared with 50 controls. Sixty-six percent of dhat syndrome patients received unspecified diagnoses on DSM-III-R. Patients with dhat syndrome showed a distinct illness behaviour profile consisting of higher scores on IBQ factors of general hypochondriasis and affective discomfort and lower scores on denial compared with controls, suggesting that the disorder may be a distinct entity. PMID- 7778473 TI - Season of birth: comparison of patients with schizophrenia, affective disorders and alcoholism. AB - The distribution of patients suffering from schizophrenia, affective disorders and alcoholism by months of their birth was studied, all patients having been reliably diagnosed using Research Diagnostic Criteria. Significant differences were found between the three groups. The winter-spring birth rate excess in schizophrenia was confirmed, a spring-summer birth rate excess in alcoholics was demonstrated. Different distributions are due to different reasons: for schizophrenic patients the harmful effects hypothesis and for alcoholics the procreational hypothesis seem to be appropriate explanations. PMID- 7778474 TI - Relationships between mental disorders in childhood and adulthood. AB - Research findings on continuities and discontinuities in psychopathology between childhood and adult life are reviewed with respect to major depressive disorders, anxiety states, obsessional conditions, anorexia nervosa, conduct disorders, hyperkinetic disorders, autism, specific developmental disorders of language and schizophrenia. The findings are used to consider both the conceptual issues and possible mediating mechanisms. PMID- 7778475 TI - Cerebral dysfunction in fibromyalgia: evidence from regional cerebral blood flow measurements, otoneurological tests and cerebrospinal fluid analysis. AB - Measurements of regional cerebral blood flow (rCBF), analysis of cerebrospinal fluid, auditory brain stem responses (ABR) and oculomotor tests were performed in 19 patients with fibromyalgia. The results from the rCBF measurements showed a normal flow level with slight but significant focal flow decreases in dorsolateral frontal cortical areas of both hemispheres. The ABR results showed signs of dysfunction at least at the brain stem level and the oculomotor tests showed high frequency of pathology. The cerebrospinal fluid analysis showed discrete changes in the cell differential count. Possible explanations for the involvement of the central nervous system in fibromyalgia are discussed. PMID- 7778476 TI - Individual coping style and psychological attitudes during pregnancy and predict depression levels during pregnancy and during postpartum. AB - Fifty primigravidae were investigated from 30 weeks of gestation until 6 months after delivery to assess the predictive value of individual coping style, conception time and specific psychological changes during pregnancy for the depression levels assessed during the third trimester of pregnancy and 5 days, 6 weeks and 6 months after delivery. The individual coping style is an effective predictor of depression levels during the third trimester of pregnancy and 6 months after delivery, but not for the depression levels 5 days and 6 weeks after delivery. A path analysis revealed that high depressive coping and low social support-seeking predict a longer conception time, which all predict a more important lack of spousal support during pregnancy. Higher depressive coping, a longer conception time and a more important lack of spousal support during pregnancy all predict high depression levels 6 months after delivery. The present findings thus suggest helpful predictors for the psychological adaptation during the transition to parenthood. PMID- 7778477 TI - Hyperthyroidism in adults: variable clinical presentations and approaches to diagnosis. AB - BACKGROUND: Hyperthyroidism is a disease that has various symptoms and can present in many ways. In the elderly patient hyperthyroidism often is not expressed in the classical manner. A case report of a middle-aged man who had hyperthyroidism with only one symptom is detailed. METHODS: A literature review utilizing MEDLINE files from 1988 to the present, as well as current textbooks of medicine and endocrinology, was used to prepare this report. Keywords for the search were "hyperthyroidism," "symptoms," "unintentional weight loss," and "differential diagnosis." RESULTS AND CONCLUSIONS: The clinical presentation of hyperthyroidism can vary from almost asymptomatic to apathetic in appearance to a marked hyperdynamic physiologic response. Family physicians must be well informed of this variation in disease expression. Overlooking the diagnosis of this relatively easily treated condition can be detrimental to patient care and expensive. PMID- 7778478 TI - Management of infants and children 0 to 36 months of age with fever without source. PMID- 7778479 TI - Obstetric privileges for family physicians: a national study. AB - BACKGROUND: We surveyed family physicians in the US to determine how many include obstetric services in their practices and to compare trends over time. METHODS: In the 1993 Practice Profile Survey, the American Academy of Family Physicians (AAFP) surveyed a random sample of active members whose mailing address was in one of the 50 states or the District of Columbia. The sample was stratified by nine census divisions; after two mailings 2460 responses were received from the 4400 physicians in the sample (56 percent response). RESULTS: Eighty-seven percent of active members had hospital admission privileges. Although there were regional disparities in the proportion of family physicians with various hospital privileges, overall 94 percent perceived that the privileges afforded them were appropriate. Approximately 26 percent of AAFP active members in 1993, compared with 29 percent in 1988, included routine obstetric care in their hospital practices. A higher proportion of family physicians in the West North Central census division had privileges at various levels of obstetric care than did family physicians in other census divisions; for example, while 57 percent of family physicians in the West North Central census division had privileges in routine obstetric care, only 9 percent of family physicians in the East South Central division had these privileges. For those family physicians who did not have privileges for any obstetric care, most indicated that they chose not to include obstetric care in their hospital practices. Family physicians most likely to have had obstetric privileges included those who practiced in nonmetropolitan areas (39 percent of family physicians had privileges in routine obstetric care compared with 21 percent in an urban setting) and those who completed a family practice residency program (33 percent with routine obstetric privileges compared with 13 percent who did not complete a 3-year residency in family practice. PMID- 7778480 TI - Acute bacterial thyroiditis secondary to urosepsis. PMID- 7778481 TI - Severe co-trimoxazole reaction in a man with AIDS. AB - Although other drugs can be used in the prophylaxis and treatment of HIV-infected persons, family physicians will prescribe co-trimoxazole frequently. These providers need to recognize the overall increased frequency of adverse reactions to this drug in this population and the potential for severe hypersensitivity effects requiring intensive hospital care. While the exact importance re-exposure has in causing this reaction remains unclear, certainly providers must pay particular attention to patients who have had any earlier sensitivity to the drug before treatment is resumed. Desensitization therapy has been used successfully in some HIV-positive individuals, even after severe reactions; however, this case again teaches the need for prudence in the use of all pharmacological agents. PMID- 7778483 TI - Clonidine as a drug of abuse. PMID- 7778482 TI - Ectopic gastric mucosa of the common bile duct. PMID- 7778485 TI - Cesarean section competence, maternity care training, and community need. PMID- 7778484 TI - Treatment of AIDS and HIV-related conditions--1995. PMID- 7778486 TI - Obstetric privileges in family practice. PMID- 7778487 TI - Family practice maternity care. PMID- 7778488 TI - Family practice maternity care. PMID- 7778489 TI - Family practice maternity care. PMID- 7778490 TI - Family practice maternity care. PMID- 7778491 TI - Canadian health care system. PMID- 7778492 TI - Children's health. PMID- 7778494 TI - Vaccine storage in the physician's office: a community study. AB - BACKGROUND: A survey was conducted of 26 physician offices and the County Health Department to determine the quality of vaccine storage. METHODS: All refrigerators were examined for secure electrical supply, firmly shut door, storage of inappropriate items, and expired vaccines. A maximum-minimum thermometer was then placed in the middle of the storage area for 24 hours, and temperatures were recorded. RESULTS: Of the 27 sites, only two had refrigerator temperatures in which both maximum and minimum temperatures fell within the acceptable range of 2 degrees to 8 degrees C. Sixty-three percent fell below minimum, 59 percent were above maximum, and 93 percent fell either below or above or both. Eight of the offices had a designated cold chain monitor, but there was no correlation with appropriate monitoring and storage of vaccines. Nine of the offices had permanent thermometers, but no correlation could be found between these sites and appropriate storage temperatures. CONCLUSIONS: A majority of vaccines in the community have been exposed to conditions that could reduce or destroy their potency. Physicians must educate their personnel in proper storage techniques of vaccines to ensure the potency of these vaccines. PMID- 7778495 TI - Relation between passive tobacco smoke exposure and the development of bacterial meningitis in children. AB - BACKGROUND: The adverse effects of passive smoking have received wide attention in recent years. Although a number of childhood illnesses are known to be affected by exposure to tobacco smoke, to date the medical literature is silent about the effect of tobacco smoke on the development of bacterial meningitis in children. The purpose of this study was to learn whether any such association exists. METHODS: Parents of 93 children admitted for bacterial meningitis were surveyed to ascertain which of the children were exposed to passive tobacco smoke. A similar survey was conducted of an age- and sex-matched control group. RESULTS: Children admitted for bacterial meningitis were significantly more likely to have been exposed to tobacco smoke than was a control group of children admitted for abdominal surgery. (P = 0.017; odds ratio 2.63, 95 percent confidence interval 1.15, 4.87). CONCLUSIONS: The results of this study indicate that bacterial meningitis in children should be added to the growing list of illnesses associated with passive exposure to cigarette smoke. PMID- 7778493 TI - Outcomes of cesarean sections performed by family physicians and the training they received: a 15-year retrospective study. AB - BACKGROUND: Family physicians are the major or sole providers of Cesarean section services in many communities. Approximately 2800 family physicians provide Cesarean section services in communities of all sizes across the country. METHODS: The outcomes of all Cesarean sections performed at two rural hospitals during a 10- to 15-year period were examined and compared with standard quality outcome criteria published in the medical literature. Outcome criteria included rates of various surgical complications, use of blood transfusion, infant Apgar scores, and length of postoperative hospital stay. Other descriptive data were examined including patient demographics, operating time, anesthesia type, and choice of incision. Statistical analysis consisted of chi-squares, odds ratios, and stepwise multiple regression. RESULTS: Five hundred sixty-three Cesarean sections were performed by 12 residency-trained family physicians, 68 by general practitioners, 70 by general surgeons, and 9 by obstetrician-gynecologists. Family physicians met or surpassed the referenced standards in all measures examined. The number of Cesarean sections each physician performed while in residency training was also examined. The average number of in-training Cesarean sections was 46, ranging from 25 to 100. CONCLUSIONS: The results of this study support the ability of family physicians to provide Cesarean section services based on a wide range of training backgrounds and variable numbers of procedures done in training. PMID- 7778497 TI - Morphological and colour mutants of Aspergillus fumigatus. AB - By using the scanning electron microscope the morphological deviations of 17 colour mutants of Aspergillus fumigatus were characterized. These mutants originated by genetic blocks in various stages of conidiophores and conidia differentiation. The complementation test was carried out with the light pigmented mutants. The group of allelic strains was found and 4 diploid strains were isolated. PMID- 7778496 TI - Obesity: a move from traditional to more patient-oriented management. AB - BACKGROUND: Family physicians have been encouraged to be aggressive in their treatment of obesity in their overweight patients. This article examines our traditional management of obesity and presents a management approach that is relatively safe, healthy, and patient-oriented. METHODS: A review of the literature on obesity and its treatment was performed by searching MEDLINE, PsychINFO, ERIC, and SOCA data bases from 1980 to 1993. Additional references were accessed by cross-referencing the bibliographies of the articles obtained through this search. RESULTS AND CONCLUSIONS: Both physicians and society in general tend to be biased against obese individuals, and this bias has negative consequences in that it reinforces patients' negative stereotypes about their fatness and could contribute to their avoidance of physicians. To circumvent this tendency, physicians should make a conscious effort to treat their obese patients with understanding and respect and to offer treatment that optimizes their risk benefit profile. Regardless of weight, all patients should be asked about their diet and exercise history, and a brief mental status evaluation should be performed to screen for eating disorders and other psychosocial disorders. In addition, all patients should be encouraged to follow a healthy lifestyle, which includes regular, moderate exercise and a balanced, low-fat diet. Repeated dieting should be avoided, because it can produce more harm than benefit by contributing to binge eating, loss of self-esteem, and increased risk of sudden death and cardiovascular disease. Thus, only obese patients who have never attempted comprehensive weight reduction programs should be encouraged to try such a program. Patients who have severe obesity that interferes with their lives or who have moderate obesity and a comorbid condition can be offered a gastroplasty or gastric bypass procedure, coupled with an explanation and discussion of the success and failure rates involved. Regardless of whether patients are able to lose weight, the family physician can still provide long term support and care and encourage a healthy lifestyle in these patients. PMID- 7778498 TI - Mutants of dermatophytes resistant to ketoconazole. AB - Authors describe the frequency and properties of mutants resistant to ketoconazole, obtained from the dermatophytes Microsporum gypseum and Trichophyton mentagrophytes. Spontaneous mutants occurred with the frequency of 10(-9) to spore and nucleus. Ultraviolet radiation increased the frequency of mutants by two numeric orders. The resistance level was relatively small in both types of mutants (RL within the range of 2-5). PMID- 7778499 TI - Effect of ketoconazole on potassium pool, c-AMP-release and ergosterol synthesis in resistant mutants of Microsporum gypseum. AB - The effect of ketoconazole (KK) on chosen biochemical indexes was studied in three mutants of dermatophyte Microsporum gypseum (MG-155 wild strain) resistant to KK. Fungistatic concentration of KK added to liquid cultivate medium increases significantly ergosterol pool and nonsignificantly demethylation activity, potassium content, cAMP release in three days old mycelium of mutants when compared to the cultivation without KK. On the contrary, there is a significant suppression of ergosterol level and demethylation activity followed by highly significant increasing of potassium content and cAMP release in the case of wild strain MG-155. PMID- 7778500 TI - Enzymatic equipment of the nasal mucosa in the developing human nasal cavity. AB - The activities of some enzymes were described in the developing human nasal cavity in relatively early stages. In cryostat sections of the 8-14-week-old fetuses processed by standard Lojda methods, activities of the following enzymes were found in the respiratory and olfactory regions: ALP, ACP, ATP, TPP, alpha GPDH, G6PDH, SDH and ANE. The positive reaction for DPP IV failed to be proved in this localization, it was not detected even in the capillary bed of the nasal cavity. PMID- 7778501 TI - [Differentiation in the human heart. I. Ultrastructural findings]. PMID- 7778503 TI - Unsaturated fatty acids incorporated in HDL in hypo- and hyperalphalipoproteinemia--relation to the HDL-cholesterol level. AB - Proportions of unsaturated fatty acids of high density lipoprotein (HDL) lipids and their relationships to the HDL-cholesterol level were compared in hypo- and hyperalphalipoproteinemic subjects. Both groups did not differ in the level of serum cholesterol. However, hypoalphalipoproteinemia was associated with hypertriglyceridemia, higher HDL-triacylglycerol level, and higher proportion of HDL-18:1 (oleic acid) and lower proportions of HDL-18:2 (linoleic acid) and 20:4 (arachidonic acid) than hyperalphalipoproteinemia. The HDL-20:4 was the only fatty acid correlating (negatively) with HDL-cholesterol. However, HDL-18:1 correlated positively and HDL-18:2 negatively with HDL-triacylglycerols, lipids related to the fall of HDL-cholesterol. These results suggest 1) an antagonism of 20:4 and 18:2 as structural components of HDL lipids in relation to the HDL cholesterol level, and 2) an association of replacement of HDL 18:2 by 18:1 with the disorder of plasma triacylglycerol metabolism. PMID- 7778502 TI - Ultrastructure of mice Leydig cells at chronic lead intoxication. AB - In the present paper we report on the study of the ultrastructure of Leydig cells of male mice after application of various doses of Pb(NO3)2 in drinking water for 2, 3, 4, 5, 7, 9 and 11 weeks. The increasing dose and time interval lead to formation of numerous concentric lamellar systems, accumulation of fatty vacuoles, vacuolization of mitochondria, pronounced surface differentiation, and changed shape of the nucleus of Leydig cells. The ultrastructural picture corresponded with an enhanced metabolic activity in some cells; in other cells dystrophic changes were observed in other. In addition to that, some cells were found that are considered by us to be an intermediary stage between the nondifferentiated mesenchymal cells and the fully functional Leydig cells. PMID- 7778505 TI - Descriptive epidemiology of tetanus in the Czech Republic in the period of 1960 1993. AB - Tetanus represented a serious health problem in the Czech Republic until 1974 with a substantial number of deaths. In the period of 1974 to 1976 a mass vaccination campaign was implemented, covering almost all adult population in both sexes. Since that time the incidence of tetanus has sharply decreased and during recent years only sporadic cases of tetanus were reported. There are some important problems pending, which are to be solved as a part of tetanus surveillance in the country. One of the most important is the occurrence of tetanus cases in fully vaccinated subjects. PMID- 7778504 TI - Some biochemical characteristics of the early phase of immunomodulation. AB - The study estimates some biochemical changes of chosen immunological and biochemical parameters after intraperitoneal application of a) immunomodulators of microbial origin--Propionibacterium acnes and Geotrichum candidum, b) chemical substances--indomethacin and phenobarbital. The estimation was concentrated above all to the changes of chemiluminiscence, phagocytic activities, the amount of cAMP in peritoneal macrophages, the amount of liver cytochrome P-450 and cAMP in the liver, spleen and thymus. The experiments also included histological examination of the spleen, thymus, lungs and diaphragm. The effect of Propionibacterium acnes was evident as soon as 24 hrs after application. In the frame of studied parameters, there was manifested the nonspecific activation of the immune system by the mechanisms independent to oxygen. The early changes were accompanied by the increase of cAMP in macrophages. In contrary, the intraperitoneal application of Geotrichum candidum activated the release of oxygen radicals from peritoneal macrophages. The amount of the cytochrome P-450 correlated to the intensity of immunomodulation. On the other hand, the induction of cytochrome P-450 by phenobarbital decreased the value of several immunity indices. PMID- 7778506 TI - Epidemiology of cryptogenic fibrosing alveolitis in Moravia and Silesia. AB - Cryptogenic fibrosing alveolitis in Moravia and Silesia (4 million inhabitants) was evaluated using standard epidemiological and clinical parameters. During 1981 1990 the incidence of cryptogenic fibrosing alveolitis ranged from 0.74 to 1.28/100,000. The trend of incidence was increasing slightly. The prevalence rose from 6.5 to 12.1/100,000. The male/female ratio was 1:1.2; 54% of patients were less than 40 years old. Biopsy (mostly open lung biopsy) supported the diagnosis in 38% of cases. During 1981-1990 years 379 new cases were detected, 488 cases altogether were registered up to 1990. The death rate calculated by incidence and prevalence was 13% and 10% resp. The mean regional incidences varied from 0.34 to 2.69/100,000, regional prevalences varied from 4.1 to 27.6/100,000. No correlation with the regional incidences of sarcoidosis and tuberculosis was found. No significant differences in coal mining areas with a high occurrence of pneumoconiosis or in areas with developed agriculture were detected. Significantly higher values were found in the regions of the four major diagnostic centres: a mean incidence of 1.58/100,000 and a mean prevalence of 20.8/100,000 (p < 0.05). The results suggest that the level of diagnostic possibilities and efforts dominates over ecological and environmental factors in the detecting of cryptogenic fibrosing alveolitis. PMID- 7778507 TI - [The so-called "complicated AV-fistula" for hemodialysis. Contribution to preoperative examinations]. PMID- 7778508 TI - [Erythrocytosis after kidney transplantation]. PMID- 7778509 TI - Possibilities of the surgery therapy of chronic pancreatitis. AB - A group of 16 patients with chronic pancreatitis was studied in this paper. All patients were treated for a long time by drug therapy on medical departments. Because of severe pain they were indicated to surgery therapy. Eleven of them were treated by derivation procedure and five by resection one. If a good indication for surgery is done the results are very satisfactory. PMID- 7778510 TI - Epileptic seizures following subarachnoideal haemorrhage. AB - An origin of epileptic seizures on the sample of 100 patients with SAH, treated at the Neurological Clinic from 1981-1993, was followed. The haemorrhage was shown by CT and/or cerebrospinal fluid. The sample consisted of 45 men and 55 women. Among the patients under 30 years of age men and over 30 women were predominant. Arterial hypertension was present in 17 cases. A positive angiographical finding of cerebrovascular malformation or aneurysm was ascertained in 38 cases. In 5 cases an early epileptic seizures with generalized convulsions occurred. Three women i.e. 3% of the sample, had late epileptic seizures occurring from 1 month to 5 years after SAH. The percentage of epileptic seizures described elsewhere is higher. PMID- 7778511 TI - EMS induced morphological and thermo-sensitive mutants of Aspergillus fumigatus. AB - The sensibility of the strain As-F2 Aspergillus fumigatus to EMS was determined by using the scale of doses. Seventeen thermo-sensitive or thermotolerant morphological mutants with decreased sporulation and growth rate as compared with a wild strain was isolated. Their more detailed characteristic will be a contents of our further paper. PMID- 7778512 TI - Encouraging faculty to use writing as a tool to foster learning in the disciplines through writing across the curriculum. AB - Writing Across the Curriculum (WAC), the national movement to infuse writing activities into the academic disciplines, promises eventually to enhance student writing competence, although its immediate goal is to foster mastery of course learning objectives. Those faculty who use WAC solely to improve writing skills assume the role of an English instructor and obligate themselves to take on an enormous amount of additional work perhaps without advancing their primary instructional missions. A limited return on this investment of effort will have the likely effect of prompting a faculty member to discard WAC. Over the long run, doing so will diminish opportunities for students to engage in productive writing experiences. Presented in this article are five strategies used in a faculty- development seminar that are designed to encourage the use of writing as an instructional tool. Individual teachers may use these strategies as justification for initiating WAC; just as important, program supervisors may use them to sustain a WAC program once it has begun. PMID- 7778513 TI - Efficiency of screening procedures for assigning levels of the Stanford Achievement Test (eighth edition) to students who are deaf or hard of hearing. AB - Assignment to an appropriate test level is crucial to the validity of standardized test scores. The present study examined the efficiency of the Reading Screening Tests and Mathematics Screening Tests developed by the Center for Assessment and Demographic Studies (CADS) of Gallaudet University for assigning levels of the Stanford Achievement Test, 8th edition (SAT-8), to deaf and hard-of-hearing students. Data were collected from programs participating in the 1990 test standardization with this population. It was found that while the screening procedures provide a credible means of assigning test levels, they are more effective for the SAT-8's Reading Comprehension, Total Language, Mathematics Computation, and Mathematics Applications subtests than for the Spelling and Concepts of Number subtests. This article concludes with recommendations in regard to individual subtest assignments. PMID- 7778514 TI - Cooperative conversations. The effect of cooperative learning on conversational interaction. AB - An ongoing challenge for educators of deaf and hard-of-hearing students is to find opportunities for students to use their language skills in a functional way, that is, through conversation. This study was initiated to determine whether cooperative learning is a viable means of encouraging mainstreamed hard-of hearing students to engage in conversational interaction with their hearing peers and teachers. A single-subject design utilizing three mainstreamed hard-of hearing subjects attending middle school was used to examine this question. Results of the study indicated that cooperative learning positively influenced the conversational turns, initiations, moves, and mean length of turn in these hard-of-hearing subjects. PMID- 7778515 TI - Partially funded mandates. PMID- 7778516 TI - In-service trends. General education teachers working with educational interpreters. AB - The "inclusion" movement has resulted in a shift of placement for children who are deaf or hard of hearing. Over 50% of students who are deaf or hard of hearing are now attending academic classes with hearing students in public school settings (Schildroth & Hotto, 1993). As the enrollment of deaf and hard of hearing students in public schools continues to increase, so does the need for qualified educational interpreters. The present study was designed to investigate nationwide the in-service training that general-education teachers receive with regard to the roles and responsibilities of educational interpreters. One hundred elementary and secondary general education teachers were surveyed, yielding a 59% return rate. Less than 33% of those teachers who returned surveys had attended in services on the topic of educational interpreters. Neither the academic level (i.e., elementary and secondary) of the teachers who participated or the number of students who were deaf or hard of hearing and in attendance at a school influenced the number of in-services provided on the topic of interpreting. PMID- 7778517 TI - Robarts revisited. PMID- 7778518 TI - On deciding to implant. PMID- 7778520 TI - Cochlear fallout. PMID- 7778521 TI - Preschool teachers' theoretical and pedagogical stances on the language and literacy development of deaf and hard-of-hearing children. Implications for teacher preparation and in-service programs. AB - This study was an investigation into three preschool teachers' theoretical and pedagogical stances on the language and literacy development of deaf and hard-of hearing children. Transcripts from formal, audiotaped interviews provided the primary data source for the investigation of the teachers' theoretical orientations toward language and literacy learning. The primary data sources used in examining the teachers' instructional practices were videotape recordings, handwritten field notes, and photographs of the teachers and their students participating in classroom language and literacy events over a six-month period. Data were analyzed inductively using the procedures and techniques related to grounded theory analysis. Results of the study indicated that the teachers held differing theories and that these theories influenced the teachers' instruction in significant ways. The study highlights the growth in one teacher's perspectives and the resulting changes in her classroom practice. PMID- 7778519 TI - Language preference and communication development of a hearing and deaf twin pair. AB - This observational study examined the development and use of communication in a pair of deaf and hearing monozygotic twins from 13 months of age until 36 months of age. One twin contracted meningitis at 7 months, leaving her profoundly deaf but without other measurable sequelae. The other twin is normal in all respects. The prelingual twins were enrolled in a total communication preschool program where, with their parents, they participated in activities designed to enhance the language skills of deaf children. The twins were videotaped monthly, first at their preschool program and later at home. All forms of communication were recorded, including signs, vocalizations, and hand and body gestures. Additionally, eye gaze direction and body positions during communication were noted. Comparisons between the deaf and hearing twins showed that although both children were able to learn language and communicate successfully, the hearing twin preferred a vocal form of language, whereas the deaf twin used mostly sign language. Moreover, the hearing twin's communication was usually responsive, while the deaf twin's communication was comprised mostly of imitative signs and gestures. Methods of teaching a profoundly deaf child to communicate are discussed. PMID- 7778522 TI - Technical report: service provision under the Individuals with Disabilities Education Act-Part H, as Amended (IDEA-Part H) to children who are deaf and hard of hearing ages birth to 36 months. Joint Committee of American Speech-Language Hearing Association and the Council on Education of the Deaf. AB - At the request of the Council on Education of the Deaf (CED) and the American Speech-Language-Hearing Association (ASHA), the Annals is publishing in its entirety and verbatim the report of a joint CED/ASHA committee designed to provide information to professionals about the services to deaf and hard of hearing children below three years of age and their families mandated by the Individuals with Disabilities Education Act-Part H, as Amended. This information should be of benefit to all professionals providing services through an individual family service plan. The report has also been published in the August, 1994 issue of the ASHA Journal. PMID- 7778523 TI - The effectiveness of an interactive instructional context. Principles from the parent-child interaction literature. AB - In the present study, the effectiveness of embedding a targeted linguistic structure within an interactive instructional context is examined. Ten subjects participated in a communication-games intervention which contained seven interactive elements drawn from the parent-child interaction literature. Ten subjects were assigned to a control group. A comparison of student performance before and after intervention supports the effectiveness of adopting instructional strategies that are consistent with a social-interaction perspective on language development. Qualitative results are presented that illustrate each of the interactional characteristics of the intervention. Implications for practice are discussed. PMID- 7778526 TI - Use of ozone generating devices to improve indoor air quality. AB - Room ozonization has been in widespread use to "freshen" indoor air for more than 100 years. This use is sometimes promoted with the claim that ozone can oxidize airborne gases, and even particulates, to simple carbon dioxide and water vapor. Aside from whether ozone can improve indoor air quality, the potentially deleterious consequences to public health of overexposure to ozone are of concern. The literature on both allegations is reviewed. It indicates that ozone is not a practical and effective means of improving indoor air quality, especially in light of its potentially serious risk to health. PMID- 7778525 TI - Hand skin temperature variations for work in moderately cold environments and the effectiveness of periodic rewarming. AB - An investigation of skin surface temperature variations under actual work conditions for four locations on the hand studied the utility of hot water immersion sinks for restoring heat to the hands during exposure to moderately cold temperatures in a food processing plant. Hand skin temperature was recorded for 15 subjects in 2 jobs with an ambient temperature of 13.3 degrees C (56 degrees F) and 1 job with an ambient temperature of 23.9 degrees C (75 degrees F). Averaged over all jobs, the mean temperature for the dorsal and palmar third finger was 17.7 degrees C (63.9 degrees F), which was significantly (p < 0.01) cooler than the mean dorsal and palmar hand temperature of 28.9 degrees C (84.0 degrees F). There was no significant difference between dorsal and palmar temperatures for either the finger or the hand (p > 0.05). In the warm environment there were no significant differences in skin temperature for any of the four hand locations (p > 0.05). An exponential model of digital warming and cooling was empirically derived using 12 subjects for predicting finger skin temperature when periodically rewarming the hands using a hot water immersion sink. The dorsal and palmar finger had a mean time constant of 151 sec for warming during immersion, 640 sec for initial cooling after a 15- to 30-min rest break at room temperature, and 198 sec for cooling after rewarming in the hot sink. The sink did not appreciably raise minimum finger skin temperature after subjects rewarmed the hands for as long as 2 min and then worked for more than 10 min without a rewarming session. PMID- 7778524 TI - Experimental considerations for the study of contaminant dispersion near the body. AB - Experimental considerations are discussed for conducting controlled studies of the dispersion of contaminants released near a mannequin. A 183 cm x 183 cm cross section wind tunnel was modified to study the low velocity range of 10 to 100 cm/sec (20 to 200 ft/min). Installation of a removable biplanar slat grid produced turbulent intensities up to 15%. The results of validation testing for selected experimental components are reported, including (1) a minimum, unambiguous velocity measurement capability of 2.0 cm/sec (4.0 ft/min); (2) a minimum required integration interval for velocity and contaminant measurements of at least 3 min; (3) a determination that smoke streamline plume settling may be a problem at velocities < or = approximately 15 cm/sec (approximately 30 ft/min); (4) a determination that a 14% tunnel blockage by the mannequin was not of consequence for frontal measurements; and (5) a finding that the biplanar grid produced turbulence spectra representative of low velocity indoor settings. A deceleration zone was noted that extended 50 cm upstream from the mannequin, with freestream velocities reduced 50 to 60%, 2.5 cm from the chest. A contaminant tracer released as a point source 60 cm upstream typically dispersed laterally only 10 to 15 cm and diluted by a factor of 10(4) before reaching the chest. PMID- 7778527 TI - Development of an ISO 9000 compatible occupational health standard: defining the issues. AB - Corporate ISO 9000 registration is gaining international acceptance as the hallmark of quality system achievement. The International Organization for Standardization (ISO) is currently drafting environmental standards that will complement ISO 9000. Should the international community also consider development of an ISO 9000-compatible occupational safety and health management standard (OSHMS)? To determine the advantages and disadvantages of this issue, the investigators conducted interviews with government and private sector experts, reviewed publicly accessible ISO documents, and evaluated published literature germane to the subject. Major advantages of an ISO OSHMS were the harmonization of national standards, maximizing Occupational Safety and Health Administration (OSHA) efficiency through third-party registration audits, and increased emphasis on employee-driven health and safety programs. Major disadvantages were the single vote of the American National Standards Institute at international proceedings, direct and indirect program development costs, potential unethical or incompetent conduct of registrars, and the logistics of developing an acceptable standard to all stakeholders. Some unresolved issues were the inevitability of an ISO OSHMS, auditor indemnification, and the scope of OSHA participation. Industrial health and safety professionals should initiate formal discussion on this issue to elaborate on findings presented here and to establish a consensus on future activities. PMID- 7778528 TI - Pharmacologic data reveal the heterogeneity of angiotensin-converting enzyme according to its source (lung versus heart). AB - Angiotensin-converting enzyme (ACE) has 2 different active sites: a C-site (in the carboxy terminal region) and an N-site (in the amino terminal part). Some ACE inhibitors have a relatively greater affinity for the C-sites, whereas others bind to the 2 sites with equal affinity. The different ontogenesis of lung and heart endothelial cells can be related to binding differences to the C- and N sites. We labeled Ro31-8472, a clizapril derivative, which has the same affinity for the 2 ACE sites. Binding of 125I-Ro31-8472 to human left ventricle and lung plasma membranes was saturable, inhibited by ethylene diaminetetraacetic acid and displayed affinities of 360 +/- 41 pM in heart and 320 +/- 51 pM in lung. For captopril the Hill slope was 0.57 +/- 0.03 for heart and 0.48 +/- 0.05 for lung; for delaprilat, a nonsulfhydryl analogue of captopril, the slope was 0.43 +/- 0.05 for heart and 0.55 +/- 0.05 for lung. These drugs were characterized by biphasic competition isotherms. The Hill slope of enalaprilat was 1.01 +/- 0.06 for heart and 0.93 +/- 0.06 for lung, and Ro31-8472 had a slope of 0.97 +/- 0.04 for heart and 0.93 +/- 0.03 for lung. The affinity of ACE inhibitors with Hill slope different from unity varied according to the source of ACE; in fact, delaprilat had greater affinity for the high-affinity sites of heart than lung (pKi, 9.89 and 9.47, respectively), whereas captopril had greater affinity for the high-affinity sites of lung than heart (9.40 and 8.85, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778529 TI - Multicenter, randomized, placebo-controlled, double-blind study of the safety and efficacy of oral delapril in patients with congestive heart failure. AB - A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. If such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. There was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily and those finishing on 15 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778530 TI - Comparison of the safety and efficacy of delapril with enalapril in patients with congestive heart failure. AB - To evaluate the safety and efficacy of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) class II and III, 198 patients were enrolled in a study in 13 centers involving a double-blind parallel group design. After completing a 2-week run-in period on placebo, patients were randomized to receive delapril 7.5 mg twice daily or enalapril 2.5 mg twice daily for 2 weeks. The dose was then doubled for the remaining 6 weeks. In this phase, 1 patient in each group experienced orthostatic hypotension; the dose was then reduced to the initial dose for study completion. A total of 195 patients received active treatment (96 delapril, 99 enalapril). After 8 weeks' treatment, bicycle ergometry demonstrated a significant increase in exercise duration (p < 0.01) and workload (p < 0.01). Echo Doppler investigations showed a significant reduction (p < 0.01) in left ventricular end-systolic volume associated with a significant increase (p < 0.01) in ejection fraction and cardiac output. No clinically significant changes in blood pressure, heart rate, electrocardiogram, or biochemical and hematologic tests were found. There were no significant differences between treatment groups. Three patients in each group experienced adverse reactions requiring withdrawal of 1 patient in each group. Delapril 15 mg twice daily, like enalapril 5 mg twice daily, was effective in improving signs and symptoms of CHF and was well tolerated. PMID- 7778531 TI - Comparison of the safety and efficacy of delapril with captopril in outpatients with congestive heart failure. AB - In this study delapril and captopril were compared in outpatients with congestive heart failure (CHF), New York Heart Association (NYHA) classes III and IV, in a double-blind study of efficacy and safety. Efficacy was evaluated by monitoring changes in the NYHA classification, exercise work, hemodynamic parameters, Kostuk's classification, and clinical signs and symptoms. Safety was monitored by a variety of laboratory tests, including renal and hepatic function, urinalysis, routine hematology testing, and the reporting of adverse events. Analysis of the data obtained revealed that delapril and captopril exhibit equal efficacy over the dosage ranges studied. There was a greater improvement of NYHA classification in terms of CHF signs and symptoms and ergometric workload in the delapril group; however, this did not reach statistical significance. The safety of the 2 drugs was also comparable, with no significant differences in any of the parameters measured at the start and end of the study. There was no statistically significant difference in the reporting of adverse events between the 2 drugs, although the sample size studied was small. There were no significant differences between the 2 drugs in terms of their effects on arterial blood pressure and no difference between prestudy and post-treatment arterial blood pressure measurements. PMID- 7778532 TI - Fundamental role of angiotensin-converting enzyme inhibitors in the management of congestive heart failure. AB - Angiotensin-converting enzyme (ACE) inhibition therapy has now become firmly ensconced in the modern therapeutic approach to all stages of congestive heart failure (CHF), including the early presymptomatic phase. Although its benefit is abundantly proven as add-on therapy in established CHF, after digitalis and diuretics, smaller and shorter studies have shown that, as second-line therapy and combined with diuretics, it may be preferable to digoxin with an undoubted benefit in postinfarction failure. As first-line therapy in early presymptomatic CHF, the evidence is also good, based on the prevention arm of the Studies of Left Ventricular Dysfunction (SOLVD), albeit in predominantly postinfarction patients, and on the Survival and Ventricular Enlargement (SAVE) study on postinfarction patients. ACE inhibitors given prophylactically or therapeutically helped to prevent clinical heart failure in the SOLVD and SAVE studies. These data suggest a role for ACE inhibitors as effective first-line monotherapy in early heart failure, acting on left ventricular function to avoid or lessen unfavorable remodeling. There are some contraindications or cautions for the use of ACE inhibitors in CHF, such as preexisting hypotension, high-renin states such as bilateral renal artery stenosis with hypertensive heart failure, aortic stenosis combined with CHF, overdiuresis with excess sodium depletion, and significant preexisting renal failure. ACE inhibition therapy may have deleterious effects on renal function in heart failure, for example, by decreasing the glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778534 TI - Safety and efficacy study of delapril versus enalapril in patients with congestive heart failure. AB - The results after the first 6 months of the 1-year treatment of this multicenter, randomized, open, parallel-group design study of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) classes II and III, are presented. The initial dose of delapril (7.5 mg twice daily) and enalapril (2.5 mg twice daily) could be doubled on a 2-weekly basis (from the beginning of the study) to a maximum of 30 mg twice daily and 10 mg twice daily, respectively. The evaluation of the efficacy was based on the changes of NYHA class, results of exercise testing involving bicycle ergometry (duration of exercise, workload, work performed, double product) performed before and after 3 months' treatment, echocardiography (left ventricular end-diastolic volume and end-systolic volume, ejection fraction, and left ventricular wall stress) at baseline and after 3 and 6 months of treatment and changes in cardiothoracic ratio, electrocardiography, and NYHA class, and patient's opinion of efficacy. Safety was evaluated by monitoring the adverse reactions, laboratory tests, and blood pressure. At 3 months, both treatments had produced a significant improvement compared with baseline in the duration of exercise, workload, and work performed in the bicycle ergometry test as well as in the ejection fraction and in left ventricular wall stress after 6 months of treatment. In addition, after 3 and 6 months of treatment, delapril produced a significant decrease in left ventricular end-systolic volume. Improvement of at least one NYHA class was observed in 20% of delapril patients and 14% of enalapril patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778533 TI - Congestive heart failure in elderly patients: controlled study of delapril versus captopril. AB - In this controlled trial, 30 elderly patients with congestive heart failure, New York Heart Association (NYHA) classes II and III, were randomly assigned to treatment with captopril 25 mg three times daily or delapril 15 mg twice daily. At the end of an 8-week treatment period, clinical symptoms of heart failure were significantly relieved by both drugs, with a consistent and statistically significant improvement in patients' quality of life evaluated using a symptoms/activity scale (p < 0.001). None of the patients was judged NYHA class III at the end of the trial and 40% were assigned to class I (p < 0.01). There was a relevant, but not statistically significant, increase in exercise duration in both treatment groups (10% captopril group, 14% delapril group), but the number of patients discontinuing the exercise test for dyspnea was 50% less in the delapril group. Neither drug had evident effects on echocardiographic left ventricular parameters. Two patients treated with captopril and 3 with delapril complained of mild-to-moderate adverse reactions. The safety of both drugs was confirmed by laboratory tests. PMID- 7778535 TI - Angiotensin-converting enzyme inhibitors in the clinical setting of chronic congestive heart failure. AB - The addition of an angiotensin-converting enzyme (ACE) inhibitor to digitalis and diuretics in chronic congestive heart failure (CHF) prolongs survival and improves the clinical condition of patients. These actions depend on the inhibition of ACE and are, therefore, common to all ACE inhibitors. Thus, the inclusion of an ACE inhibitor in the therapeutic regimen of chronic CHF is mandatory, whenever feasible. The use of ACE inhibitors in chronic CHF should avoid symptomatic hypotension and inordinate decreases in renal function. To this end, ACE inhibitor therapy should progress by gradually increasing doses, and sodium intake and dosages of diuretics and ACE inhibitors should be adjusted in the light of changing circumstances. ACE inhibitors with short elimination half lives should be preferred in chronic CHF, since they allow quicker dose adjustment than their longer-acting congeners, and given that compliance with once and twice daily dosing would be similar. PMID- 7778536 TI - Pharmacokinetic and pharmacologic properties of delapril, a lipophilic nonsulfhydryl angiotensin-converting enzyme inhibitor. AB - Delapril is a carboxy-alkyl-dipeptide mainly converted in animals and humans to an active diacid derivative (M-I), which in turn is converted to an active 5 hydroxy-indane diacid (M-III). In humans these metabolites are excreted in the urine. The presence of the indanyl-glycine moiety gives delapril a high lipophilicity, greater than several other angiotensin-converting enzyme (ACE) inhibitors, such as captopril and enalapril. Due to its greater lipophilicity, delapril has been shown to exert a more effective inhibition of vascular ACE than captopril and enalapril, both in vitro and in vivo. The activity of delapril on tissue ACE also lasts longer than on the circulating enzyme. At doses ranging from 1-10 mg/kg orally, delapril exerts a marked and long-lasting antihypertensive action in various experimental models of hypertension. The blood pressure reduction has been shown to be accompanied by suppression of angiotensin II release from the vascular wall. In stroke-prone spontaneously hypertensive rats (SHR-SP) and in SHR with chronic renal failure, besides reducing hypertension, delapril significantly improves survival rate and prevents the development of stroke, cardiac hypertrophy, and renal sclerosis. The ability of delapril to reduce hypertrophy in vascular and cardiac tissue has been demonstrated in both in vitro and in vivo experiments. PMID- 7778537 TI - Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective results from the Quebec Cardiovascular Study) AB - In 1985, plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and plasma apoprotein (apo) B levels were measured in 2,103 men (aged 45 to 76 years) without ischemic heart disease from the Quebec city suburbs. Occurrence of a first ischemic event (i.e., angina pectoris, acute myocardial infarction, or coronary-related death) was recorded in 114 men between 1985 and 1990. Men with and without ischemic heart disease were classified as normal or in various dyslipidemic groups according to an established algorithm. Of the 1,989 men who remained free of ischemic events, 50% had a normal lipid profile compared with 32% in men with ischemic heart disease. Although the prevalence of type IIb and IV dyslipidemias was similar in men with and without ischemic heart disease, type IIa (16% vs 10%), hyperapo B-hypertriglyceridemia (12% vs 6%), hyperapo B normotriglyceridemia (11% vs 7%), and hypoalphalipoproteinemia (18% vs 13%) were more prevalent in men with than without ischemic heart disease. Adjusted odds ratios (ORs) were not increased in type IIb and IV phenotypes, whereas men with type IIa (OR 2.8), with the 2 hyperapo B phenotypes (hyperapo B normotriglyceridemia, OR 2.7; hyperapo B-hypertriglyceridemia, OR 3.1) or with isolated hypoalphalipoproteinemia (OR 2.2), were at higher risk. The results of this prospective study confirm the importance of both elevated plasma cholesterol and decreased high-density lipoprotein cholesterol levels as risk factors for ischemic heart disease. They also emphasize the high prevalence of an elevated apo B dyslipidemic state in ischemic heart disease. PMID- 7778539 TI - Trends in acute myocardial infarction prognosis and treatment in southwestern France between 1985 and 1990 (the MONICA Project-Toulouse). AB - Since 1984, the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA project) has studied progress in acute coronary artery disease (CAD) in defined geographic areas. This study, based in a French MONICA center in Southwestern France, assessed acute myocardial infarction (AMI) frequency, prognosis, and treatment between 1985 and 1990. The age-standardized AMI attack rate showed a slight decrease in men (218.3 of 100,000 in 1985 and 200.1 of 100,000 in 1990, p < 0.05). In men, the AMI age-standardized 28-day case fatality rate decreased from 38% in 1985 to 27% in 1990 (p < 0.001), with a dramatic reduction in the age-standardized in-hospital case fatality rate (21% in 1985 and 11% in 1990, p < 0.001). Furthermore, the in-hospital 28-day case fatality decreased exclusively in male patients with a history of CAD (33% in 1986 and 19% in 1990, p < 0.01). AMI treatment improved between 1986 and 1990 with increased use of antiplatelets (40.7% in 1986, 73.6% in 1989, and 84.8% in 1990, p < 0.001), beta-blockers (29.5% in 1986, 45.7% in 1989, and 57.7% in 1990, p < 0.001), and thrombolytic therapy (23.6% in 1986, 45.3% in 1989, and 39.5% in 1990, p < 0.001). Invasive cardiology technique utilization increased dramatically between 1986 and 1990 with the generalized use of coronary angiography (68.2% in 1986, 89.3% in 1989, and 87.3% in 1990, p < 0.001) and percutaneous transluminal coronary angioplasty (17.7% in 1986, 49.6% in 1989, and 55.3% in 1990, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778538 TI - Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group. AB - In the present study we measured fasting lipid profiles in over 8,500 community living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol. PMID- 7778540 TI - Electrocardiographic diagnosis of reperfusion during thrombolytic therapy in acute myocardial infarction. AB - Continuous 12-lead electrocardiographic monitoring was performed in 61 patients receiving thrombolytic therapy for an acute myocardial infarction. Coronary angiography within 90 minutes revealed a patent vessel (Thrombolysis in Myocardial Infarction [TIMI] trial 2 or 3) in 44 patients. Early signs of reperfusion were ST-segment normalization (likelihood ratio 16.0), development of terminal T-wave inversion (likelihood ratio 10.6), accelerated idioventricular rhythm (likelihood ratio 6.0), and a twofold increase in ventricular premature complexes (likelihood ratio 2.5). Relief of chest pain after 60 minutes was reported by 96%. During reperfusion of the infarct-related vessel, an increase in ST-segment deviation was recorded in 61% of the patients, whereas 69% had an increase in chest pain preceding the eventual decline. PMID- 7778541 TI - Psychosocial factors related to unrecognized acute myocardial infarction. AB - Acute myocardial infarction (AMI) often is unrecognized (i.e., a patient fails to notice or report the event to the physician, or the physician fails to diagnose it). Psychosocial differences between patients with recognized and unrecognized AMI have not been examined. We compared 40 patients who sought treatment for a documented AMI with 30 patients who were found on routine electrocardiogram to have had an AMI for which they did not seek medical care. Patients with unrecognized AMI showed greater "alexithymia," or deficient psychologic awareness (p = 0.04; Alexithymia Provoked Response Interview), and a greater belief that chance factors determine their health (p = 0.004; Multidimensional Health Locus of Control Scale). Patients with unrecognized AMI were less likely to have angina, yet did not differ from those with recognized AMI with regard to demographics, smoking, systemic hypertension, diabetes mellitus, AMI location, depression, or hypochondriasis. We hypothesize that deficient psychologic awareness may impede AMI symptom perception or recognition, and that the belief in chance or fate as determining health may inhibit treatment-seeking. PMID- 7778542 TI - Comparison of sestamibi single-photon emission computed tomography with positron emission tomography for estimating left ventricular myocardial viability. AB - Technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi [MIBI]) is distributed in the myocardium according to blood flow. Reports comparing stress rest sestamibi protocols with reinjection thallium or resting fluorodeoxyglucose (FDG), or both, in patients with coronary artery disease have shown appreciable discordance regarding myocardial viability in these settings. We performed this analysis with regard to regional comparisons within discordant segments and made comparisons in a subset of patients who underwent revascularization. Thirty-seven patients with coronary artery disease had single-photon emission computed tomography MIBI, N-13 ammonia/18FDG positron emission tomography (PET), and radionuclide ventriculography performed at rest. One hundred two segments were viable and 29 were nonviable by both MIBI and FDG. The concordance was 71%. In MIBI nonviable/FDG viable segments, most of the discordance was in the inferior wall. In MIBI nonviable discordant segments, FDG accurately predicted an increase in percent regional ejection fraction (preoperative 36% [+/- 5 SE] to postoperative 48% [+/- 5.5 SE][p < 0.0006]). MIBI underestimates myocardial viability as assessed by PET. Seventy-one percent of myocardial segments were concordant by both quantitative sestamibi single-photon emission computed tomography and FDG PET. Discordance in MIBI nonviable segments was predominantly in the inferior wall. PET can be helpful in detecting myocardial viability in patients suspected of having had MIBI nonviability in the inferior wall. PMID- 7778543 TI - Design of the Beta-Blocker Evaluation Survival Trial (BEST). The BEST Steering Committee. AB - Central to our current understanding of heart failure is the concept that compensatory mechanisms that maintain blood pressure and perfusion ultimately contribute to worsening of ventricular function. Studies of the effect of angiotensin-converting enzyme inhibitors in patients with heart failure are consistent with this paradigm. This manuscript describes a 2,800-patient randomized trial that will definitively determine whether sympathetic nervous system antagonism with a beta blocker prolongs the life of patients with moderate to severe heart failure. PMID- 7778544 TI - Lipoprotein(a) distribution in a French Canadian population and its relation to intermittent claudication (the Quebec Cardiovascular Study) AB - This study was undertaken to evaluate the distribution and the relation of lipoprotein(a) (Lp[a]) concentration with intermittent claudication in a cohort of men aged 35 to 64 years, randomly selected in 1974 and followed until 1990. In 1985, blood samples for a complete fasting lipid profile and Lp(a) were obtained in 2,424 men representing 62% of the living cohort. The diagnosis of intermittent claudication was made by trained nurses using a standardized questionnaire and confirmed by a cardiologist. Lp(a) distribution did not change with age and was similar to that of other Caucasian populations. Because Lp(a) concentration did not vary with age, its relation to the incidence of intermittent claudication was assessed for the years 1974 to 1990. The incidence of intermittent claudication was 42 of 10,000 person-years. The 113 men with intermittent claudication, in contrast to men without this symptomatology, were older at entry (49 +/- 7 vs 45 +/- 7 years), and had higher systolic pressure (144 +/- 20 vs 136 +/- 16 mmHg) and Lp(a) levels (46 +/- 45 vs 33 +/- 35 mg/dl) (all p < 0.05). There was also a significantly greater prevalence of smoking and diabetes among men with intermittent claudication. The risk of intermittent claudication was doubled in men in the second and third tertiles of Lp(a) concentration (p < 0.001). Thus, high Lp(a) levels constitute a significant risk for intermittent claudication in this population. PMID- 7778545 TI - Long-term outcomes and modes of death of patients treated with nonthoracotomy implantable defibrillators. AB - Long-term outcomes of all patients who underwent nonthoracotomy implantable cardioverter-defibrillator (ICD) implantation at our institution from April 1991 to October 1994 were studied using the intention-to-treat analysis. Of 94 consecutive patients, 81 underwent nonthoracotomy ICD implantation and 13 underwent thoracotomy (for concomitant surgery in 11 and unavailability of nonthoracotomy leads in 2). Six of 81 patients had a high defibrillation threshold, 4 subsequently underwent thoracotomy, and 2 were treated with amiodarone. Surgical mortality was 0%. The duration of follow-up was 20 +/- 13 months, and was > 12 months in 74% of 67 living patients. Actuarial survival rates at 1 and 2 years were, respectively, 98% and 94% for sudden death and 91% and 83% for total mortality. Deaths during long-term follow-up were mostly due to nonsudden cardiac or noncardiac deaths. Two-year mortality rates were 12% and 25% in patients with ejection fraction > or = 30% and < 30%, respectively. Thus, instances of sudden death and surgical mortality are very few in patients with nonthoracotomy ICDs. Deaths during long-term follow-up are mostly due to nonsudden cardiac and noncardiac deaths. Therefore, ICD therapy may have greater impact on survival in patients with lower risks of nonsudden cardiac and cardiac death (e.g., younger patients with minimal heart disease) than in patients with severe cardiac or noncardiac disease. Prospective studies are needed to address this question. PMID- 7778546 TI - Relation between electrocardiography and echocardiography for left ventricular mass in mild systemic hypertension (results from Treatment of Mild Hypertension Study). AB - Clinical recognition of hypertensive cardiac involvement depends primarily on use of noninvasive methods. The performance of 8 electrocardiographic (ECG) criteria sets were compared with an echocardiographic standard in the treatment of Mild Hypertension Study. Electrocardiograms were computer processed to define the following ECG criteria sets: (1) Casale/Devereux, (2) Cornell product, (3) Cornell voltage, (4) 12-lead voltage product, (5) sum of 12-lead voltage, (6) Rautaharju, (7) Sokolow-Lyon, and (8) Romhilt-Estes. Echocardiographic left ventricular (LV) mass index was calculated by using the Penn convention on a biracial population of 834 men and women. Correlations between ECG and echocardiographic LV mass index were modest (<0.40). ECG-LV hypertrophy sensitivity at 95% specificity was < 34%. The Casale/Devereux ECG criteria showed the highest average sensitivity (17%) at 95% specificity for all race-sex groups. Whites had significantly higher correlation values than blacks. ECG correlations with LV mass index were consistently improved by including systolic blood pressure and body mass index. ECG criteria sets appear to be optimized for white men. The study findings confirm the poor ECG sensitivity and correlation with echocardiographic LV mass and suggest: (1) further refinement of ECG criteria alone in white men is unlikely to improve its relationship with LV mass; and (2) combining the electrocardiogram with other non-ECG variables or noninvasive measurements offers the best strategy for improving ECG sensitivity and its prognostic value. PMID- 7778547 TI - Relation between diurnal variation of blood pressure and left ventricular mass in a Chinese population. AB - In western populations, patients with hypertension who have a nocturnal decrease in blood pressure (BP) may have less left ventricular (LV) hypertrophy and cardiovascular morbidity than those without a diurnal variation in BP. To further examine this association between nocturnal BP reduction and LV mass index, we studied 720 normotensives (< 140/90 mm Hg), 380 borderline hypertensives (140 to 159/90 to 94 mm Hg), and 582 hypertensives (> or = 160/95 mm Hg) from Taiwan and Quemoy island by using 24-hour ambulatory BP monitoring and 2-dimensional echocardiography to obtain LV mass index during a community-based cardiovascular survey. After controlling for age, sex, height, weight, daytime BP, and daytime heart rate, the nocturnal reduction of systolic BP was found to associate weakly with LV mass index, for the whole population (partial correlation coefficient = 0.06, p < 0.05), as well as for the patients with hypertension (partial correlation coefficient = -0.09, p < 0.05), but these associations were eliminated when 24-hour BP and heart rate were accounted for. The average and percent nocturnal decrease of systolic BP (mean +/- SD; mm Hg, [%]) of 3.2 +/- 5.9 (2.7 +/- 4.8%); 3.3 +/- 7.3 (2.4 +/- 5.4%); and 4.6 +/- 9.0 (3.0 +/- 6.1%) in normotensives, borderline hypertensives, and hypertensives, respectively, was smaller than that found in previous studies. Hence, in this large Chinese population, a small nocturnal BP drop was found and it was only weakly associated with LV mass index. These results emphasize the general need for ambulatory BP reference values based on internal controls. PMID- 7778549 TI - Quantitation of cardiac output with velocity-encoded, phase-difference magnetic resonance imaging. AB - Velocity-encoded, phase-difference magnetic resonance imaging (MRI) previously has been used to measure flow in the aorta, as well as in the pulmonary, carotid, and renal arteries, but these measurements have not been validated against currently accepted invasive techniques. To determine the accuracy of velocity encoded, phase-difference MRI measurements of cardiac output, 23 subjects (11 men and 12 women, aged 15 to 72 years) underwent velocity-encoded, phase-difference MRI measurements of cardiac output in the proximal aorta, followed immediately by cardiac catheterization, with measurement of cardiac output by the Fick principle and by thermodilution. For MRI, Fick, and thermodilution measurements, stroke volume was calculated by dividing cardiac output by heart rate. The magnetic resonance images were acquired in 1 to 3 minutes. For all patients, the agreement between measurements of stroke volume was 3 +/- 9 ml for MRI and Fick, -3 +/- 11 ml for MRI and thermodilution, and 0 +/- 8 ml for MRI and the average of Fick and thermodilution. Compared with standard invasive measurements, velocity-encoded, phase-difference MRI can accurately and rapidly determine cardiac output. PMID- 7778548 TI - Lack of long-term ventricular arrhythmia reduction by enalapril in heart failure. SOLVD Investigators. AB - Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction < or = 35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 +/- 13 vs 84 +/- 13/hour), 4 months (100 +/- 15 vs 85 +/- 12/hour), or 12 months (80 +/- 12 vs 90 +/- 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 +/- 4.1 vs 1.9 +/- 0.4 runs/day), 4 months (16 +/- 12 vs 7.2 +/- 4.1 runs/day), or after 12 months of blinded therapy (11 +/- 7.0 vs 6.1 +/- 4.4 runs/day).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778550 TI - Feasibility and accuracy of Doppler echocardiographic estimation of pulmonary artery occlusive pressure in the intensive care unit. AB - Mitral inflow and pulmonary vein inflow variables have been shown to relate to left ventricular filling pressures. However, the feasibility and accuracy of Doppler estimation of pulmonary artery (PA) occlusive pressure in the intensive care unit have not been previously assessed. Accordingly, 67 consecutive patients in intensive care units who had PA catheters underwent Doppler recordings of mitral inflow, pulmonary vein flow, and isovolumic relaxation time (IVRT). Thirty six patients met Doppler inclusion criteria. Most exclusions were due to atrial fibrillation, merging of peak velocity during early diastole (E) and atrial contraction (A) mitral flow velocities, and inadequate recordings. Mean age (+/- SD) was 65 +/- 12 years, ejection fraction varied between 19% and 80%, and 45% of patients were on mechanical ventilation. Doppler-derived variables were related to occlusive pressure (mean 16 +/- 6 mm Hg, range 6 to 40), and the most significant variables were entered into a multiple linear regression analysis. The derived relation was tested in 30 repeat studies after a variety of hemodynamic interventions and in a prospective group of 32 additional patients (mean age 63 +/- 11.6 years, pressure range 7 to 28 mm Hg). The highest correlations with occlusive pressure were observed with the E/A ratio (r = 0.75), IVRT (r = -0.55), atrial filling fraction (r = -0.65), and deceleration time (r = -0.50). Pulmonary venous recording could be obtained in only 16% of patients. The best model was with E/A and IVRT: PA occlusive pressure = 17 + (5.3 E/A)-(0.11 IVRT), r = 0.79.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778551 TI - Is there anything to add to our lipid risk factors for coronary heart disease? PMID- 7778552 TI - Increased susceptibility of angiographically smooth left anterior descending coronary artery to an impairment of vasoresponse to acetylcholine, and the relation between impaired vasoresponse and low-density lipoprotein cholesterol level. AB - In the present study, we demonstrated that the angiographically smooth LAD is more susceptible than the LC to an impairment of vasoresponse to acetylcholine, suggesting the more severe endothelial dysfunction in the LAD. We also showed that levels of LDL play a partial but important role on endothelial dysfunction. PMID- 7778553 TI - Reproducibility of the intravascular ultrasound assessment of stent implantation in saphenous vein grafts. AB - IVUS measurements of stent and reference lumen dimensions and cross-sectional areas are highly reproducible. Furthermore, paramedical personnel can be trained to perform these measurements accurately. Thus, IVUS measurements may become the gold standard for the acute, chronic, and serial assessment of stent implantation procedures. PMID- 7778555 TI - Serial changes in left ventricular diastolic indexes derived from Doppler echocardiography after anterior wall acute myocardial infarction. AB - Restrictive ventricular filling pattern derived from Doppler echocardiography after anterior wall AMI may serve as an indicator of diastolic dysfunction due to initial myocardial stiffness and complications such as extension of the infarction, Dressler syndrome, septal rupture, or myocardial failure. Later changes, such as prolongation of deceleration time, may indicate remodeling process, healing of the complications of AMI, or improved revascularization. PMID- 7778554 TI - Usefulness of mitral regurgitation in protecting against left ventricular thrombus after acute myocardial infarction. AB - In conclusion, we documented an increased incidence of LV thrombus in patients with MR after AMI. PMID- 7778556 TI - Usefulness of an abnormal signal-averaged electrocardiogram for predicting cardiac death in elderly persons without heart disease. AB - We found an abnormal signal-averaged ECG in 7 of 51 elderly patients (14%) (mean age 83 years) without clinical evidence of heart disease, and in 1 of 25 volunteers (4%) (mean age 31 years range [17 to 47]) without clinical evidence of heart disease. The data from our prospective study indicate that at 43-month mean follow-up, elderly patients with an abnormal signal-averaged ECG but no clinical evidence of heart disease do not have an increased incidence of sudden cardiac death, total cardiac death, or total death. PMID- 7778557 TI - Effect of combined 17 beta-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. AB - In conclusion, combined administration of 17beta-estradiol and vitamin E protects LDL in postmenopausal women from oxidation with no synergism noted compared with either therapy given alone. PMID- 7778558 TI - Are gender differences in QTc present at birth? MISNES Investigators. Multicenter Italian Study on Neonatal Electrocardiography and Sudden Infant Death Syndrome. AB - The analysis of 9,725 electrocardiograms recorded on the fourth day of life has shown that gender-related differences in QTc observed in the adult population are not present at birth. PMID- 7778559 TI - Use of adenosine-sensitive nondecremental accessory pathways in assessing the results of radiofrequency catheter ablation. AB - Adenosine can cause conduction block in about 20% of nondecremental accessory pathways. Along with atrial activation mapping, adenosine may help differentiate retrograde AV node conduction versus residual accessory pathway conduction after radiofrequency catheter ablation; however, it is important to test the accessory pathway response to adenosine before ablation, particularly with a concealed accessory pathway. PMID- 7778560 TI - Role of endothelin in the exercise intolerance of chronic heart failure. AB - In conclusion, plasma levels of the endothelial-derived vasoconstrictor endothelin-1 (but not those of other neurohormonal vasoconstrictor factors), measured during exercise correlated closely with objective variables of exercise capacity in patients with heart failure. These findings suggest that endothelin-1 may contribute to exercise intolerance in patients with heart failure, perhaps by limiting the ability of the peripheral vasculature to dilate during exercise. PMID- 7778562 TI - Pulmonary and systemic venous flow patterns assessed by transesophageal Doppler echocardiography in congenital absence of the pericardium. AB - In conclusion, alterations in venous return are more marked in the right side of the heart than in the left side of the heart in patients with complete absence of the left pericardium. PMID- 7778561 TI - Comparison of thallium-201 myocardial single-photon emission computed tomography and cine magnetic resonance imaging in Duchenne's muscular dystrophy. AB - In conclusion, thallium-201 myocardial SPECT is useful not only in detecting myocardial degeneration and estimating cardiac functions, but also in predicting the prognosis of cardiomyopathy in patients with Duchenne's muscular dystrophy. PMID- 7778563 TI - Initial experience with percutaneous transhepatic cardiac catheterization in infants and children. AB - Percutaneous transhepatic cardiac catheterization is a straightforward procedure that can be performed by experienced pediatric interventionalists with little additional training. We believe that this technique can be a valuable tool in the treatment of selected patients with complex congenital heart defects. PMID- 7778564 TI - An experimental model examining the role of magnesium in the therapy of acute myocardial infarction. AB - In conclusion, considering the results from our model, magnesium infusion is effective as adjunct therapy to enhance myocardial salvage in the setting of acute myocardial infarction. However, its effectiveness may be limited to a subset of patients whose magnesium therapy can be started early and combined with early reperfusion therapy. PMID- 7778565 TI - Anomalous origin of the left main pulmonary artery from the ascending aorta associated with DiGeorge syndrome. AB - We place on record 2 infants with the DiGeorge syndrome and anomalous origin of the left pulmonary artery from the ascending aorta. We postulate that: (1) embryogenesis of anomalous origin of the left pulmonary artery from the ascending aorta might be due to the persistent fifth aortic arch connecting both arterial systems; (2) an anomalous pulmonary artery arising from the ascending aorta is part of the aortic arch abnormality accompanied by normal conotruncal septation; and (3) in the DiGeorge syndrome, cardiac anomalies that originate from the conotruncus or aortic arch, or both, may have the same embryologic mechanisms. PMID- 7778566 TI - ACP Community-Based Teaching Project. PMID- 7778567 TI - ASIM: building ties between medical practice and academia. PMID- 7778568 TI - The revision of government-sponsored health care. PMID- 7778569 TI - Capitated Medicaid and the process of care of elderly hypertensives and diabetics: results from a randomized trial. AB - PURPOSE: To measure the quality of care for hypertensive and diabetic elderly Medicaid beneficiaries enrolled in managed care versus fee-for-service (FFS) plans. METHODS: Individuals enrolled in the Medicaid Demonstration Project in Hennepin County, Minnesota, were randomly assigned to receive their care either in one of seven managed care health plans in which the Medicaid payment for their care was capitated or in an FFS plan. Two hundred ninety-one hypertensives and 96 diabetics who were aged 65 years or over at the beginning of the evaluation were interviewed at baseline and followed for 1 year. Drug and nondrug therapy, monitoring, monthly medication costs, and access to medications were assessed. RESULTS: The prepaid and FFS did not differ in drug or nondrug therapy, with the exception that slightly more FFS enrollees were on human insulin after 1 year. Mean monthly medication costs and access to medications were similar for both groups. CONCLUSIONS: In this randomized trial, we were unable to detect differences in the process of care for hypertensive and diabetic Medicaid enrollees. PMID- 7778570 TI - Methodologic sources of inconsistent prognoses for post-acute myocardial infarction. AB - PURPOSE: To investigate basic methodologic problems that could explain inconsistent and contradictory results for predictor variables in studies of prognosis after myocardial infarction (MI). MATERIALS AND METHODS: Studies on postinfarct prognosis published in English between 1979 and 1991 were identified with a MEDLINE literature search. The key words used for the computer search were: "prognosis" and "myocardial infarction" in the title and "mortality" or "survival" or "outcome" in the title or abstract. Reference lists in the reports captured by the search were examined for pertinent articles, and additional articles were sought in the index pages of two prominent journals. To be included in the analysis, a study had to fulfill the following eligibility criteria: a cohort study or randomized, controlled trial; sample size > or = 50 patients; a clear identification of the time when follow-up began, after the acute phase of MI and either before or at hospital discharge; follow-up for a minimum of 6 months or median/mean of 1 year; and multivariable analysis for intervals no longer than 2 years after the MI. Eight methodologic standards addressing sources of major problems were established and applied to each study. RESULTS: Of 766 reports identified, 111 fulfilled the eligibility criteria. The median number of standards fulfilled was 3, the highest 6. The proportions of studies complying with each of the 8 methodologic standards were: (1) inception cohort, 60%; (2) total death as an unequivocal outcome, 54%; (3) verification of cause-specific deaths (in 62 studies analyzing cardiac death), 37%; (4) analysis of crucial variables describing baseline severity, 13%; (5) indication of quantitative scope of the spectrum of baseline severity, 20%; (6) reproducible classification of candidate predictor variables, 40%; (7) adequate identification of quantitative importance of and boundaries for statistically significant predictor variables, 39%; and (8) evaluation of impact of treatment on predictor variables, 13%. CONCLUSIONS: The results show that studies on postinfarct prognosis have frequently disregarded basic methodologic principles. Suitable adherence to these principles in future research will allow improved interpretation of results and can reduce inconsistent findings, while improving the applicability of the identified predictors. PMID- 7778571 TI - Accuracy of anticardiolipin antibodies in identifying a history of thrombosis among patients with systemic lupus erythematosus. AB - OBJECTIVE: To measure the accuracy of anticardiolipin antibodies (aCL) in identifying a history of thrombosis among patients with systemic lupus erythematosus (SLE) or the primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS: Patients with SLE or PAPS who attended our rheumatology clinic between April 1992 and March 1994 were included in a retrospective analysis of the relationship between thrombotic events and aCL. All aCL measurements were performed in the same laboratory by enzyme-linked immunosorbent assay, blinded as to the presence or absence of thrombosis. The diagnostic accuracy of IgG, IgM, and IgA aCL was quantified by means of the receiver operating characteristic area under the curve (ROC AUC) for each isotype. Stratum-specific likelihood ratios and their 95% confidence intervals were calculated to define strata with optimal discriminant power. RESULTS: During the period of study, aCL was measured in 117 patients (113 SLE and 4 PAPS), of whom 24 (20.5%) had experienced thrombotic events. The ROC AUC +/- the standard error for IgG aCL was 0.81 +/- 0.05, signifying an 81% accuracy in the identification of a history of thrombosis. In contrast, the accuracy of the IgM and IgA aCL was significantly lower (0.60 +/- 0.08 and 0.54 +/- 0.07, respectively, P < 0.05). Using stratum-specific likelihood ratios, we defined three strata in the IgG aCL scale that discriminate between patients with low, indeterminate, and high probabilities of thrombosis. For IgG aCL levels below 21.4 IgG phospholipid (GPL) U/mL, the posttest probability of thrombosis was 0.07, whereas for IgG aCL levels > or = 65.1 GPL U/mL, the posttest probability of thrombosis was 0.75. For IgG aCL values between 21.4 and 65.0 GPL U/mL, the probability of thrombosis was 0.20, equivalent to the entire cohort. CONCLUSIONS: The IgG aCL determinations perform well in the identification of thrombosis in SLE or PAPS, while the IgM and IgA aCL have poor diagnostic accuracy. These findings may have implications for management of these patients. PMID- 7778573 TI - Extensive bone marrow necrosis associated with antiphospholipid antibodies. AB - Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis. PMID- 7778572 TI - Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance. AB - PURPOSE: To establish the frequency with which serum ferritin levels > or = 1,000 ng/mL occur in a general hospital population, and to determine the clinical significance of this finding. PATIENTS AND METHODS: All serum ferritin determinations performed between June 1992 and July 1993 at the University of Cincinnati Medical Center were reviewed and patients with serum ferritin levels > or = 1,000 ng/mL identified. The medical records of these patients were then reviewed. RESULTS: Of 1,826 serum ferritin determinations performed during the study period, 122 (6.7%) were > or = 1,000 ng/mL. Associated clinical syndromes found in the 95 patients with serum ferritin > or = 1,000 ng/mL included liver disease (20.0%), renal disease (17.9%), malignant disease (17.9%), human immunodeficiency virus (HIV) infection (16.8%), non-HIV systemic infections (15.8%), chronic transfusions (10.5%), and sickle cell syndromes (10.5%). No syndrome usually associated with extreme serum ferritin elevations was identified in 8.4% of patients, and 16.8% of the patients fell into more than one category. The highest mean serum ferritin levels occurred in the chronically transfused and sickle cell groups. Concomitant serum transferrin saturation values were determined with 82 (86.3%) of the elevated serum ferritin levels and did not correlate well with them. The highest mean transferrin saturation levels occurred in the liver disease group. Transferrin saturation > or = 50%, suggestive of iron overload, was significantly more frequent in the liver disease group (P = 0.002); and saturation < or = 15%, suggestive of iron-deficient erythropoiesis, was significantly more frequent in the HIV group (P = 0.001). CONCLUSION: Outside the setting of clinical syndromes associated with iron overload (liver disease, transfusions, sickle cell syndromes), serum ferritin levels > or = 1,000 ng/mL serve as a nonspecific marker for a variety of significant disorders, including infectious and neoplastic diseases. Further study of the regulation of ferritin production may provide insight into the pathogenesis of disorders associated with extreme serum ferritin elevations. PMID- 7778574 TI - Heparin-induced aldosterone suppression and hyperkalemia. AB - PURPOSE: To review the effects of heparin and heparinoid compounds on aldosterone physiology and associated induction of hyperkalemia. MATERIALS AND METHODS: A comprehensive literature search (of human and animal data) was carried out by computer and by using reference citations from primary sources. RESULTS: Heparin and its congeners are predictable, potent inhibitors of aldosterone production. This inhibitory effect is specific for the zona glomerulosa; other corticosteroids are not affected. Aldosterone suppression occurs within a few days of initiation of therapy, is reversible, and is independent of either anticoagulant effect or route of administration. Decreases in aldosterone levels may occur with heparin dosages as low as 5,000 U BID. The most important, but probably not the only mechanism of aldosterone inhibition appears to involve reduction in both the number and affinity of the angiotensin-II receptors in the zona glomerulosa. Prolonged use of heparin causes marked reduction in the width of the adrenal zona glomerulosa. CONCLUSIONS: Aldosterone suppression results in natriuresis and less predictably in decreased excretion of potassium. Greater than normal serum potassium levels occur in about 7% of patients, but marked hyperkalemia generally requires the presence of additional factors perturbing potassium balance (in particular, renal insufficiency, diabetes mellitus, or the use of certain medications). Heparin-induced increases in serum potassium need to be better anticipated by clinicians. Serum potassium levels should be monitored periodically in patients being given heparin for 3 or more days, and in patients at relatively high risk for hyperkalemia, the monitoring interval should probably be no greater than 4 days. PMID- 7778575 TI - Doctor talk: technology and modern conversation. PMID- 7778576 TI - Sustained response in Felty's syndrome to prolonged administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). PMID- 7778577 TI - A case of severe cytolysis after hepatitis B vaccination. PMID- 7778578 TI - Measuring HIV-1 infection among needle/syringe exchange attenders. PMID- 7778579 TI - Gender: measuring its influence on senior medical students' "professional personality" and career choice. PMID- 7778580 TI - Methicillin-resistant Staphylococcus aureus. PMID- 7778581 TI - Liver damage in patients with CSF-producing tumors. PMID- 7778582 TI - Case report of dapsone-related thrombocytosis in an AIDS patient. PMID- 7778583 TI - Prenatal diagnosis and fetopathological findings in five fetuses with trisomy 9. AB - Five male fetuses with trisomy 9 are discussed. Three were detected prenatally and terminated, 1 aborted spontaneously, and the fifth delivered prematurely and died soon after. Multiple congenital abnormalities characteristic of trisomy 9 were detected in all 5 cases and are compared to those of previous reports. PMID- 7778584 TI - Trisomy 9: review and report of two new cases. AB - Trisomy 9 is a relatively uncommon chromosome abnormality that may sometimes be seen in the nonmosaic state. We reviewed 23 mosaic and 15 nonmosaic cases of trisomy 9, including 2 new cases, in order to better define the prognosis and phenotype of this disorder. A recognizable trisomy 9 phenotype was identified and included a "bulbous" nose, microphthalmia, and dislocated limbs. Other nonspecific anomalies involving various organ systems were also common. With one exception, all survivors had severe mental impairment. Mosaicism for trisomy 9 predicted longer survival, but the degree of mosaicism in lymphocytes or fibroblasts did not predict survival or degree of impairment. Parental chromosome variations were not uncommon. In contrast to prior reports, no specific prognostic finding was identified. A meiotic origin with loss of a trisomic cell line in mosaic cases is suggested. PMID- 7778586 TI - Unusual case of Smith-Lemli-Opitz syndrome "type II". AB - We describe a fetus with abnormalities suggestive, but not typical, of severe Smith-Lemli-Opitz syndrome (SLO). Biochemical studies demonstrated that there was a defect of cholesterol biosynthesis similar to that recently discovered in children with SLO. The findings in this fetus extend even further the wide spectrum of abnormalities of the SLO phenotype, and emphasize that a genetic pathological examination and biochemical studies should always be undertaken on atypical cases, especially fetuses. PMID- 7778585 TI - Trisomy 9 syndrome: report of a case with Crohn disease and review of the literature. AB - We report on a 6-year-old boy with mosaic trisomy 9. The patient was born at 42 weeks of gestation to a 27-year-old G1 white woman. Birth weight was 2,820 g, length 52 cm, and Apgar scores were 4 and 6 at 1 and 5 min, respectively. The infant presented with apparently low-set ears, overfolded helices, epicanthal folds, prominent nasal bridge, high-arched palate, micrognathia, bilateral dislocated hips, left genu recurvatum, and cryptorchidism. Chromosome analysis showed an unusual karyotype: 47,XY,+inv(9qh+)/47,XY,+mar. The marker chromosome was thought to be a remnant of the inv(9qh+) chromosome. The mother's karyotype was 46,XX,inv(9qh+), while the father's was 46,XY. At age 5 months, the patient developed seizures and gastroesophageal reflux. Crohn disease was diagnosed at age 2 years, although symptoms began at age 1 year. Recurrent bouts of pneumonia have occurred since the patient's birth. Severe psychomotor retardation was also noted. Trisomy 9 syndrome was first reported in 1973. Over 30 cases have been reported since then. Of these cases reports, only 5 patients were older than 1 year. Inflammatory bowel disease has been reported in association with other chromosome abnormalities, but to our knowledge, has not been reported in trisomy 9 syndrome. PMID- 7778587 TI - Prenatal diagnosis of Smith-Lemli-Opitz syndrome. AB - An abnormality in cholesterol synthesis was described recently in the Smith-Lemli Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis. We also discuss the possible use of this test in detecting heterozygotes. PMID- 7778588 TI - Smith-Lemli-Opitz syndrome: prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid. AB - Until recently, the diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was made on the basis of clinical criteria alone. As a result, prenatal diagnosis has been possible only if sonography disclosed distinct fetal malformations in a subsequent pregnancy. However, the recent description of increased levels of 7-dehydrocholesterol (cholesta-5,7-dien-3 beta-ol) in patients with SLOS, most likely caused by a deficiency of 3 beta-hydroxysteroid-delta 7-reductase, has provided an apparently reliable biochemical marker for diagnosis of SLOS. To determine if this abnormality of sterol metabolism has utility for prenatal diagnosis of SLOS, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLOS was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7 dehydrocholesterol in plasma. Quantitative analysis by gas chromatography of sterols extracted from the amniotic fluid of both pregnancies revealed similar, markedly increased levels of 7-dehydrocholesterol and its precursor, lathosterol (cholest-7-en-3 beta-ol), both of which were undetectable in reference amniotic fluids. These findings suggest that abnormalities of cholesterol biosynthesis in SLOS may be sufficiently expressed in fetal life to permit prenatal diagnosis of this disorder by measurement of 7-dehydrocholesterol in amniotic fluid. PMID- 7778589 TI - Severe Smith-Lemli-Opitz syndrome with prolonged survival and lipid abnormalities. AB - We have studied a girl with multiple congenital anomalies, growth and mental deficiency, characteristic facial anomalies, cataracts, cerebellar atrophy, and severe hypocholesterolemia. Death occurred at age 7 years. After excluding several syndromes, i.e., peroxisomal disorders, mevalonic acidaemia, and Marinesco-Sjogren syndrome, it is concluded that this girl had severe Smith-Lemli Opitz Syndrome (SLOS) with exceptionally long survival. This diagnosis was confirmed through assay of 7-dehydrocholesterol in cultured fibroblasts. PMID- 7778590 TI - Prenatal detection of the cholesterol biosynthetic defect in the Smith-Lemli Opitz syndrome by the analysis of amniotic fluid sterols. AB - The Smith-Lemli-Opitz (SLO or RSH) syndrome is an autosomal recessive disorder characterized by a recognizable pattern of minor facial anomalies, congenital anomalies of many organs, failure to thrive, and mental retardation. Its cause is a defect in cholesterol biosynthesis characterized by abnormally low plasma cholesterol levels and concentrations of the cholesterol precursor 7 dehydrocholesterol (7DHC) elevated up to several thousand-fold above normal. We used capillary column gas-chromatography to quantify sterols in amniotic fluid, amniotic cells, plasma, placenta, and breast milk from a heterozygous mother who had previously given birth to an affected son and in cord blood and plasma from her affected newborn daughter. The cholesterol concentration in amniotic fluid at 16 weeks gestation was normal, but 7DHC, normally undetectable, was greatly elevated. In cultured amniocytes, the level of 7DHC was 11% of total cholesterol, similar to cultured fibroblasts from patients with SLO syndrome. At 38 weeks, a girl with phenotype consistent with the syndrome was born. Cholesterol concentrations were abnormally low in cord blood and in the baby's plasma at 12 weeks, while levels of 7DHC were grossly elevated, confirming the prenatal diagnosis. The mother's plasma cholesterol increased steadily during gestation but remained below the lower 95% limit reported for normal control women. We conclude that it is now possible to detect the SLO syndrome at 16 weeks gestation by analyzing amniotic fluid sterols. PMID- 7778591 TI - Prenatal diagnosis of Smith-Lemli-Opitz syndrome. PMID- 7778592 TI - Concerning "Agamanolis disease". PMID- 7778593 TI - Inconsistencies in pedigree symbols in human genetics publications: a need for standardization. AB - To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree's basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations. PMID- 7778594 TI - De novo tandem duplication of chromosome segment 22q11-q12: clinical, cytogenetic, and molecular characterization. AB - We report on a case of duplication of the segment 22q11-q12 due to a de novo duplication. Molecular cytogenetics studies demonstrated this to be a tandem duplication, flanked proximally by the marker D22Z4, a centromeric alpha satellite DNA repeat, and distally by D22S260, an anonymous DNA marker proximal to the Ewing sarcoma breakpoint. The segment includes the regions responsible for the "cat-eye," Di George, and velo-cardio-facial syndromes and extends distal to the breakpoint cluster region (BCR). The clinical picture is dominated by the cardiac defects and includes findings reminiscent of "cat-eye" syndrome. These findings reinforce the hypothesis that the proximal 22q region contains dosage sensitive genes involved in development. PMID- 7778595 TI - Histopathology of fetal diastrophic dysplasia. AB - We report on three cases of diastrophic dysplasia in second trimester fetuses and discuss the differential diagnosis and clinical, radiologic, and histopathologic findings. Manifestations of typical diastrophic dysplasia in infants and older patients include abnormal pinnae, scoliosis, and joint contractures; these were absent in the fetuses, in keeping with the tendency for the clinical and radiologic aspects of this disease to become more severe with age. The histopathologic characteristics of the cartilage appear to be similar in the fetus and older patient, and therefore may be useful in differentiating diastrophic dysplasia from other osteochondrodysplasias in the second trimester. PMID- 7778596 TI - Web neck anomaly and its association with congenital heart disease. AB - To investigate the relationship between congenital heart disease and jugular lymphatic obstruction as manifested in web neck anomaly, we used the Iowa Birth Defects Registry to determine the incidence of congenital heart defects (CHD) in infants with and without web neck. Sixty percent of infants with web neck had CHD, with a high incidence of flow-related defects such as hypoplastic left heart, coarctation, and secundum atrial septal defect. Sixty-eight percent of infants with web neck had a genetic syndrome (37% Down syndrome, 13% Ullrich Turner syndrome, and 5% Noonan syndrome), and 24% had dysmorphic features consistent with lymphatic obstruction sequence. When infants with Down, Ullrich Turner, and Noonan syndrome and web neck were compared to infants with the same syndrome but without web neck, those with web neck were significantly more likely to have flow-related heart defects. Infants with Ullrich-Turner syndrome and web neck had an 11-fold higher incidence of coarctation, compared to those with a normal neck. Our data suggests web neck is associated with both flow and nonflow related heart defects. This association implies a pathogenetic relationship and appears to be independent of causal factors. The finding of web neck or nuchal cystic hygroma on a prenatal ultrasound or newborn examination should prompt a search for CHD. PMID- 7778597 TI - Further study of genetic interactions: loss of short arm material in patients with ring chromosome 4 changes developmental pattern of del(4)(q33). AB - Segment 4q33 is not considered a probable location of a gene related with limb deficiency by Roberts and Tabin [Am J Hum Genet 55:1-6, 1994]; however, the occurrence of ectrodactyly or its equivalents in at least 9 published cases of monosomy 4q33 suggests probable location of one of these genes in that region. Ulnar ray defects and/or ectrodactyly were the prevailing forms. An additional loss of the tip of 4p in patients with ring chromosome 4 leads to a change of limb deficiency type: 8 of 9 patients with r(4) and limb deficiency had radial ray defects. Therefore, interactions between a proposed 1/2 dose "ectrodactyly" gene on 4q33 and some 1/2 dosage genes on distal 4p (or disturbed cellular homeostasis due to a ring chromosome 4) can change the developmental pattern of limb deficiency. Possible mechanisms and significance of the phenomenon are discussed. PMID- 7778598 TI - Autosomal recessive Melnick-Needles syndrome or ter Haar syndrome? Report of a patient and reappraisal of an earlier report. AB - We report on a patient with congenital glaucoma, brachycephaly with flat occiput, large anterior fontanel, hypertelorism, anteverted nostrils, thoracolumbar kyphosis, prominent coccyx with skin fold, short hands and feet, flexion deformity of fingers, and clubfeet. He had a double-outlet right ventricle with ventricular septal defect, and severe tricuspid insufficiency. Mild skeletal changes included short tubular bones, absence of distal phalanges of toes, caliber variation of ribs, and scalloping of the anterior surface of vertebrae. The patient died at age 21 months. He belongs to the same extended family as 3 similarly affected patients, previously described by ter Haar et al. [1982: Am J Med Genet 13:469-477] as representing an autosomal recessive form of Melnick Needles syndrome. We believe this diagnosis is no longer tenable. After having reviewed the relevant literature, we conclude that most probably we are dealing with a new autosomal recessive syndrome. We propose to name this entity ter Haar syndrome. PMID- 7778599 TI - Multiple congenital malformations in two sibs reminiscent of hydrolethalus and pseudotrisomy 13 syndromes. AB - We report on two sibs, born to consanguineous parents, with defects of the midline including cleft lip and palate, flat nose, hypotelorism, and dysgenesis of corpus callosum, in addition to short limbs, radiolucent tibial notch, digital anomalies, ambiguous genitalia, and hypopituitarism. In spite of the similarities between this condition and the hydrolethalus and pseudotrisomy 13 syndromes, our patients had neither preaxial nor postaxial polydactyly, but had previously undescribed bilateral radiolucent tibial notch, which is not known to be part of those two syndromes. The cases presented here may very well represent a new autosomal recessive syndrome. PMID- 7778600 TI - Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome. AB - We report on a macrosomic newborn girl with albinism, a black lock at the right temporo-occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory-evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine, and total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the 14th child of consanguineous Kurdish parents. Four sibs of our patient had the same syndrome and died a few days after birth. The other 9 sibs are well, with an unremarkable phenotype. A syndrome of albinism, black lock, deafness, and a total lack of intestinal neural innervation has not yet been reported. It represents a new neural crest syndrome with autosomal-recessive inheritance. PMID- 7778601 TI - Brief clinical report on a deletion 5q35.3. PMID- 7778603 TI - Asperger syndrome in a boy with a balanced de novo translocation: t(17;19)(p13.3;p11) PMID- 7778602 TI - Further patient with Angelman syndrome due to paternal disomy of chromosome 15 and a milder phenotype. PMID- 7778604 TI - Lipomatosis and partial lipohypoplasia in Proteus syndrome: a clinical clue for twin spotting? PMID- 7778605 TI - Craniosynostoses: phenotypic/molecular correlations. PMID- 7778606 TI - Sound-alike cephalosporins. How drugs with similar spellings and sounds can lead to serious errors. PMID- 7778607 TI - Managing pain from pressure ulcers. PMID- 7778608 TI - Insights into conscious sedation. PMID- 7778609 TI - Branching out into home care. PMID- 7778610 TI - Back to basics. Would you hang these i.v. solutions? PMID- 7778611 TI - Using imagery to help your patient heal. PMID- 7778612 TI - Clinical snapshot: deep vein thrombosis. PMID- 7778613 TI - The revolution in health care. What's your readiness quotient? PMID- 7778615 TI - Choosing a life insurance policy. PMID- 7778617 TI - Seeing forever. PMID- 7778614 TI - Emergency: autonomic dysreflexia. PMID- 7778616 TI - Leverage, exploitation, and intellectual capital. PMID- 7778618 TI - Shoes. PMID- 7778619 TI - Trial of labor after cesarean delivery with a lower-segment, vertical uterine incision: is it safe? AB - OBJECTIVE: Our purpose was to assess maternal and perinatal outcomes associated with a trial of labor and attempted vaginal birth after prior low-segment vertical cesarean delivery. STUDY DESIGN: During a 10-year period in a single tertiary hospital, all patients with a prior low-segment uterine incision (whether vertical or transverse) were considered candidates for a trial of labor in the absence of other contraindications or patient refusal. Among the 1137 women who underwent low-segment vertical cesarean delivery, 262 were subsequently delivered of 322 live-born infants, and 174 (54%) of them were identified retrospectively as having attempted vaginal birth. The maternal and perinatal outcomes of patients who did or did not undergo a trial of labor were analyzed and compared. RESULTS: No significant differences between the two patient groups were observed regarding demographic characteristics, antepartum complications, gestational age at delivery (mean 37.4 weeks), birth weight, and cord pH at delivery. Vaginal delivery was accomplished successfully in 144 of 174 (83%) patients who underwent a trial of labor. Abdominal delivery was necessary for 17 mothers with labor disorders and 13 with suspected fetal distress. Postpartum hemorrhage occurred more often in the trial of labor group (7/174 [4.0%] vs 2/148 [1.4%], p not significant), but endometritis developed significantly more often in patients with elective repeat cesarean delivery (16.9% vs 6.3%, p = 0.006). Rupture of the low-segment vertical cesarean scar occurred in 2 patients during a trial of labor (1.1%) versus none in the elective repeat cesarean group. Neither mother experienced fetal extrusion or adverse maternal or fetal sequelae. Frequency of serious neonatal complications (8.1% vs 10%) and neonatal mortality (1.7% vs 2.0%) were similar between groups. All neonatal deaths were a result of extreme prematurity or congenital anomalies. CONCLUSIONS: Our experience indicates that a mother with a prior low-segment vertical cesarean delivery can undertake a trial of labor with relative maternal-perinatal safety. The likelihood of successful outcome and the incidence of complications are comparable to those of published experience with a trial of labor after a previous low-segment transverse incision. PMID- 7778620 TI - Uterine prolapse complicated by endometrial cancer. AB - OBJECTIVE: An infrequent clinical dilemma arises when a patient with uterine prolapse that is best treated vaginally is discovered to have coexisting endometrial cancer. Often the underlying cancer is only discovered intraoperatively or postoperatively. We have reviewed our experience in this situation in an effort to evaluate efficacy of treatment, strategies to avoid late postoperative discovery of cancer, and general guidelines for optimal treatment. STUDY DESIGN: At the Mayo Clinic from 1950 to 1993, 54 patients with coexisting endometrial carcinoma underwent vaginal hysterectomy with repairs for uterine prolapse. RESULTS: We have retrospectively reviewed these cases for relevant data and survival analysis. Complete follow-up is available for 53 patients, and there were four recurrences. In 19 patients bilateral oophorectomy was not performed for multiple reasons, and one of these patients had a recurrence. Twenty-five percent of all patients had disease confined to the endometrium, and 80% overall had low-grade lesions with superficial or no myometrial invasion. Of the four recurrences, three would have been considered low risk of extrauterine spread, and it is doubtful that an abdominal approach would have yielded additional useful information. No patient required reoperation for recurrent pelvic relaxation. CONCLUSION: We believe that for certain selected patients vaginal surgery for uterine prolapse is adequate treatment in the presence of endometrial cancer. We discuss the selection strategies, exclusion criteria, and general guidelines to optimize care for these challenging patients. PMID- 7778621 TI - Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious. AB - OBJECTIVE: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases. STUDY DESIGN: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp excited dye laser photothermolysis. RESULTS: Dye laser response rates were independent of whether patients manifested macroscopic foci of painful erythema ("vestibular adenitis") or just colposcopically apparent hyperemia-ectasia of the individual blood vessels ("pruritic papillomatosis") (56% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the "surface only" group and 80.3% in the "surface-plus-deep" group (chi 2 = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery. CONCLUSION: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. PMID- 7778623 TI - The medical and economic impact of laparoscopically assisted vaginal hysterectomy in a large, metropolitan, not-for-profit hospital. AB - OBJECTIVE: Our purpose was to evaluate the medical and economic impact of of operative laparoscopy on the surgical approach to hysterectomy for benign disease in a large, metropolitan, not-for-profit hospital. STUDY DESIGN: Retrospective analyses were performed on 2563 hysterectomies (without vaginal or bladder repair) for benign disease, performed by 37 gynecologists between January 1991 and December 1993. Disposable laparoscopic instruments and stapling devices were not used at any time during the study period. Electrosurgery and sutures were used for hemostasis. Parameters analyzed included surgical approach (total abdominal hysterectomy, vaginal hysterectomy, laparoscopically assisted vaginal hysterectomy, and failed laparoscopically assisted vaginal hysterectomy), operative time, postoperative diagnosis, operative blood loss, length of stay, complications, uterine weight, and hospital changes. Charges in each of these parameters were analyzed and compared in 6-month increments. RESULTS: During the study period the percent of hysterectomies performed abdominally declined from 65% to 36%. Laparoscopically assisted vaginal hysterectomy increased from 12% to 45%, and vaginal hysterectomy varied from 23% to 19%. Average operative time was 82 minutes (+/- 2 minutes) for total abdominal hysterectomy, 102 minutes (+/- 2.3 minutes) for laparoscopically assisted vaginal hysterectomy, and 63 minutes (+/- 2 minutes) for vaginal hysterectomy. Hospital stay was 68 hours (+/- 1.5 hours) for total abdominal hysterectomy, 44 hours (+/- 1.2 hours) for laparoscopically assisted vaginal hysterectomy, and 43 hours (+/- 4.1 hours) for vaginal hysterectomy. The average hospital charge was $6552 (+/- $108) for total abdominal hysterectomy, $6431 (+/- $100) for laparoscopically assisted vaginal hysterectomy, and $5869 (+/- $116) for vaginal hysterectomy. CONCLUSIONS: Contrary to previously published studies, our study demonstrates (1) laparoscopically assisted vaginal hysterectomy is a cost-effective procedure when performed with reusable instruments, (2) laparoscopically assisted vaginal hysterectomy is a safe procedure, even when performed by a variety of gynecologists with different skill levels, and (3) the number of hysterectomies performed abdominally was decreased by 29% without incurring more complications or reducing the number of vaginal cases. PMID- 7778622 TI - Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin. AB - OBJECTIVE: Our purpose was to evaluate the effectiveness of oxytocin, prostaglandin E2 intracervical gel, and estradiol cream for ripening the very unfavorable cervix in patients requiring induction of labor at term. STUDY DESIGN: This prospective, randomized study was conducted in a population of women with a very unfavorable cervix (Bishop score < 4) requiring induction of labor. The patients received prostaglandin E2 gel (0.5 mg) intracervically (three doses 6 hours apart), 4 mg estradiol cream in the anterior fornix of the vagina (three doses 6 hours apart), or oxytocin at induction per protocol with an infusion pump. RESULTS: Ninety-nine women were recruited into this trial and evenly distributed among the three groups. The demographics of maternal age, race, parity, gestational age, initial Bishop score, and indication for induction were similar among the groups. The incidence of cesarean deliveries was similar in the three groups with approximately 59% of pregnancies delivered abdominally. For patients undergoing abdominal delivery the maximum cervical dilatation among the oxytocin, estradiol, and prostaglandin E2 groups was similar (3.90 +/- 3.02 cm, 3.63 +/- 2.79 cm, and 4.65 +/- 2.78 cm, respectively; p > 0.05). For all patients birth weight and Apgar scores at 1 and 5 minutes were comparable across all regimens (p > 0.05). In the subset of patients delivered vaginally patients receiving oxytocin for cervical ripening had the greatest improvement in Bishop score over baseline (p = 0.023) with an improvement of 7.08 +/- 2.42. CONCLUSION: No differences were detected among prostaglandin E2 gel, estrogen, and oxytocin in relation to cervical ripening in patients with an unfavorable cervix at term who require an induction of labor. Patients with a very unfavorable cervix at term who require delivery may benefit from serial ripening and inductions. PMID- 7778624 TI - Primary and preventive care in a university obstetrics and gynecology group practice. AB - OBJECTIVE: Our purpose was to determine whether primary and preventive care is practiced by a university obstetrician-gynecologist group practice. STUDY DESIGN: A retrospective chart review spanning 2 years of four academic physicians' private practices was performed. A total of 335 patients were reviewed with 739 patient encounters and 1032 patient problems identified. The definition of a primary care physician according to The American College of Obstetricians and Gynecologists was used to standardize data collection and evaluation. RESULTS: Obstetric complaints accounted for 27.7% of all visits, whereas 65.4% were for gynecologic problems. Almost 7% of all complaints were neither obstetric nor gynecologic, and of those 74.6% were primary care problems completely managed by the obstetrician-gynecologist. Only 19.7% of these were referred for management. More than 89% of all encounters (659/739) involved some element of primary care. CONCLUSION: This study provides evidence that the majority of health care provided by the obstetrician-gynecologist is primary care. PMID- 7778625 TI - Incisional bowel herniations after operative laparoscopy: a series of nineteen cases and review of the literature. AB - OBJECTIVES: The objectives of this report were (1) to identify all cases of incisional bowel herniations noted after operative laparoscopy in 11 participating institutions and (2) to report the clinical details of such patients. STUDY DESIGN: A retrospective case review was performed. RESULTS: Nineteen cases of incisional bowel herniation were identified. The average age of the patients was 50.5 years. Initial laparoscopic procedures varied and included laparoscopically assisted vaginal hysterectomy (six patients), laparoscopically assisted vaginal hysterectomy with lymphadenectomy (five patients), oophorectomy (two patients), adhesiolysis (two patients), myomectomy (two patients), lymphadenectomy alone (one patient), and ovarian cystectomy (one patient). The average time to reoperation was 8.5 days. CONCLUSIONS: Incisional bowel herniation is a serious complication of operative laparoscopy. Herniations occur through ports > or = mm in size at both umbilical and extraumbilical sites. New techniques are needed to avoid this serious complication. PMID- 7778627 TI - The accuracy of antenatal fetal echocardiography screening in high- and low-risk patients. AB - OBJECTIVE: The purpose of this study was to evaluate the accuracy of four-chamber and left ventricular outflow tract views in low-risk patients and comprehensive fetal echocardiographic examinations in high-risk patients to diagnose structural heart disease or thoracic anomalies. STUDY DESIGN: A prospective outcome study of two cohorts was performed; 1136 low-risk patients and 886 high-risk patients were evaluated during a 2-year period. Low-risk patients underwent routine four chamber and left ventricular outflow tract evaluation whereas high-risk patients had detailed fetal echocardiographic examinations. Accuracy of the ultrasonographic diagnosis was evaluated from neonatal discharge data. RESULTS: Only 2 of 14 patients with congenital heart disease in the low-risk group were correctly identified (sensitivity 14.3%) whereas 10 of 16 patients with congenital heart disease or thoracic anomalies were correctly identified in the high-risk group (sensitivity 62.5%). CONCLUSION: The current study showed poor diagnostic accuracy of the standard four-chamber and left ventricular outflow tract views in low-risk patients for the diagnosis of structural cardiac anomalies. Patients with risk factors for congenital heart disease should be referred for comprehensive fetal echocardiographic examination. PMID- 7778626 TI - Preterm external cephalic version in an outpatient environment. AB - OBJECTIVE: Our purpose was to study the safety and efficacy of external cephalic version before term (37 weeks' gestation). STUDY DESIGN: We retrospectively reviewed 114 pregnancies in 110 women at 30 to 41 weeks' gestation who had a total of 133 attempts at external cephalic version. RESULTS: Seventy-nine percent of the versions performed before the thirty-seventh week and 53% performed during or after the thirty-seventh week were successful. After adjustment parity and body mass index, a version performed before the thirty-seventh week was 27 times more likely to be successful than if performed during or after the thirty-seventh week. Ninety-nine percent of the successful versions were delivered with a vertex presentation, and of these only 16% required cesarean delivery. CONCLUSION: External cephalic version is safe and successful if performed before 37 weeks' gestation, hence substantially reducing the rate of cesarean section among nonvertex presentations and reducing the risks associated with breech delivery. PMID- 7778629 TI - Time-quantified fetal movement detection with two-transducer data fusion. AB - OBJECTIVE: Our purpose was to develop an automated ultrasound-based fetal movement detection system to better define fetal movements. STUDY DESIGN: One hundred one patients had fetal movements recorded over a 20-minute period. Results of movement detection by a single-transducer system (Russell 1) and a two transducer fusion system (Russell 2) were compared with those of Hewlett-Packard (HP-M-1350-A), maternal perception, and expert ultrasonography review. RESULTS: A total of 86,592 seconds of videotape was scored for fetal movement. Russell 2 had a second-per-second sensitivity of 57.21% compared with Russell 1 at 40.95%, the HP-M-1350-A at 31.44%, and maternal perception at 30.80%. Russell 2 detected 67.57% of discrete movements compared with 57.52%, 41.98%, and 37.92%, respectively, in other systems. CONCLUSION: Russell 2 represents a significant improvement over existing systems in detection of fetal movements on a second-per second basis. PMID- 7778628 TI - Evolving patterns of iatrogenic multifetal pregnancy generation: implications for aggressiveness of infertility treatments. AB - OBJECTIVE: Our purpose was to assess the changes in multifetal pregnancy generation as a function of utilization of ovulation stimulation and assisted reproductive techniques and to document the relative control of hyperstimulation between the methods. STUDY DESIGN: The methods of infertility treatment, number of fetuses, and outcomes of 220 patients referred for multifetal pregnancy reduction were compared over three time periods (1986 to 1989, 1991 to 1992, and 1992 to 1993). Clomiphene, human menopausal gonadotropin, and ovulation stimulation with urofollitropin were compared against gamete intrafallopian transfer, zygote intrafallopian transfer, and in vitro fertilization (assisted reproductive techniques). RESULTS: The proportion of multifetal pregnancies generated by assisted reproductive techniques has steadily risen from 26% in the first two time periods to nearly half in the last 2 years. However, the number and proportion of quintuplet and greater pregnancies from assisted reproductive techniques have steadily fallen while for ovulation stimulation the proportion has remained about one third. CONCLUSION: Despite considerably increased use and proportionate generation of triplet and quadruplet pregnancies, the incidence of quintuplets has fallen for assisted reproductive techniques while there has been no improvement for ovulation stimulation. Continued, greater vigilance, particularly in the use of human menopausal gonadotropin and urofollitropin, must be emphasized. PMID- 7778630 TI - Underappreciated risks of the elderly multipara. AB - OBJECTIVE: Our purpose was to identify the age-related increased risks of the elderly gravida by clarifying the effects of age and parity, their combination, and their interaction. STUDY DESIGN: We studied 9556 singleton pregnancies in women aged 20 to 29 years or > or = 35 years delivered over an 8-year period. Data were analyzed by stepwise multiway contingency table analysis, with p < 0.002 considered significant. RESULTS: Many of the previously reported risks of the elderly gravida are expected on the basis of age and parity. Significant associations (primarily related to advanced age) included higher frequencies of obesity, chronic hypertension, gestational diabetes, and large-for-gestational age and macrosomic infants. These elderly gravidas, on the other hand, had fewer postdates pregnancies. Although often overlooked, the greatest age-related increases in risk for induction (1.8 times), preeclampsia (2.7 times), gestational diabetes (4.5 times), clinical diabetes (3.2 times), oxytocin use (1.7 times), and macrosomia (1.6 times) occur in multiparas, not nulliparas. The risk for preeclampsia in the elderly multipara is significantly higher than expected on the basis of age and parity. CONCLUSION: The increased risks of the elderly multipara may have been overshadowed by the previous focus on the elderly nullipara. It is important to recognize the increases in age-related risks of the elderly multipara to appropriately counsel and manage this group of patients. PMID- 7778631 TI - The effect of tocolytic use in the management of symptomatic placenta previa. AB - OBJECTIVE: The null hypothesis is that tocolysis has no effect on pregnancy prolongation in the aggressive expectant management of symptomatic preterm placenta previa. STUDY DESIGN: One hundred twelve preterm pregnancies with confirmed placenta previa and an initial episode of acute vaginal bleeding were selected for this retrospective analysis. Exclusion criteria included gestational age > or = 35 weeks, delivery within 24 hours of admission, prior treatment for bleeding or preterm labor, and contraindications to tocolytic use. Tocolysis was prescribed, at the discretion of the treating clinical staff, in selected pregnancies with significant uterine contractions after admission of the patient. The majority of treated patients (85%) received intravenous magnesium sulfate and/or oral or subcutaneous beta-sympathomimetics within 24 hours of admission. Most patients remained hospitalized until delivery under this aggressive expectant management protocol. Both treated and untreated control study groups were similar at inclusion with regard to parity, gestational age, contraction frequency, and degree of initial bleeding. Outcome variables for each treatment group were obtained from final chart review. Continuous and categoric variables were compared with Student t test or chi 2 analysis-Fisher's exact test, respectively. RESULTS: The clinical use of tocolysis in symptomatic placenta previa was associated with a clinically significant delay of preterm delivery. Significant improvement in clinical parameters such as interval from admission to delivery (39.2 vs 26.9 days, p < 0.02) and birth weight (2520 vs 2124 gm, p < 0.03) was observed in the tocolysis group. There was no observed statistical difference between the two treatment groups with regard to incidence of recurrent bleeding, interval from admission to first recurrent bleeding, and need for transfusion. There was a trend for patients with multiple bleeding episodes to have been receiving tocolytic therapy (p < 0.10). A trend for requiring a postpartum transfusion was also noted in the tocolysis group (p < 0.09). Treated pregnancies receiving long-term maintenance tocolysis with oral or subcutaneous terbutaline exhibited a greater degree of pregnancy prolongation than those treated with short-term intravenous magnesium alone (43.7 vs 15.3 days, p < 0.02). CONCLUSIONS: This retrospective analysis suggests that tocolytic intervention in cases of symptomatic preterm previa may be associated with clinically significant prolongation of pregnancy and increased birth weight. Tocolytic therapy in these cases does not appear to have an impact on frequency or severity of recurrent vaginal bleeding. Further prospective analysis may delineate the role of tocolysis in the aggressive expectant management of symptomatic placenta previa. PMID- 7778632 TI - Magnetic resonance imaging of defects in DeLancey's vaginal support levels I, II, and III. AB - OBJECTIVE: The aim was to demonstrate paravaginal defects at DeLancey's levels I, II, and III by pelvic magnetic resonance imaging scanning in patients with symptomatic pelvic relaxation preoperatively and to demonstrate the disappearance of such defects after surgical repair. STUDY DESIGN: Magnetic resonance imaging scans of the pelvis were performed in 12 patients exhibiting cystourethroceles and symptomatic urinary stress incontinence. RESULTS: Magnetic resonance imaging scans of bilateral fascial defects at the upper third of the vagina (level I) were unremarkable except for the constant "chevron sign," whereas the middle third of the vagina (level II) displayed the "saddlebags sign," and the lower third of the vagina (level III) displayed the "mustache sign." These defects disappeared postoperatively. CONCLUSIONS: Bilateral defects in the paracolpium at vaginal support levels I, II, and III may be found by magnetic resonance imaging scans before surgery in certain patients with symptomatic pelvic relaxation. Postoperative scans after paravaginal repair demonstrate the disappearance of these defects. PMID- 7778633 TI - Neonatal outcome after preterm delivery for preeclampsia. AB - OBJECTIVE: Our purpose was to determine whether maternal preeclampsia per se has a beneficial effect on neonatal outcome after delivery before 35 weeks. STUDY DESIGN: A matched cohort study design was used. Two hundred twenty-three infants of strictly defined preeclamptic women were matched for gestational age, race, gender, and mode of delivery with infants of normotensive women with preterm labor and delivery. Pregnancies with multiple gestation, premature rupture of membranes, known fetal anomalies, diabetes, or maternal medical disease were excluded. Information was obtained by review of maternal and neonatal charts. Paired categoric and continuous data were compared by McNemar's test and the Wilcoxon signed-rank test, respectively. RESULTS: There was no difference in the incidence of neonatal death (4.5% vs 4.5%, p = 0.82), respiratory distress syndrome (22.0% vs 22.0%, p = 0.88), grades 3 and 4 intraventricular hemorrhage (2.2% vs 2.2%, p = 0.72), grades 2 and 3 necrotizing enterocolitis (5.8% vs 4.0%, p = 0.48), and culture-proved sepsis (9.0% vs 9.0%, p = 0.85). Results were similar when analysis was limited to infants born at < or = 32 weeks, infants born to mothers with severe preeclampsia, and infants with intrauterine growth restriction. CONCLUSION: Maternal preeclampsia per se does not have a beneficial effect on the postnatal course of infants born at 24 to 35 weeks' gestation. PMID- 7778634 TI - The expert witness: real issues and suggestions. AB - Medical malpractice lawsuits generally require expert testimony. Defendants and plaintiffs deserve expert testimony that is exacting, accurate, and consistent. A study of four frequently testifying experts was undertaken with review of depositions, reports, and trial transcripts of those experts. Contradictions in claimed medical principles from one case to the next were found and examples were cited for each expert. The review suggested that expert testimony regarding the standard of care may be neither reliable nor accurate for the purposes of judging physician conduct is lawsuits. Presently, no peer review or sanction process has been implemented to ensure accuracy and reliability of expert testimony used in medical malpractice lawsuits. We recommend changes that would include independent court-appointed experts, central filing of opinion letters by experts with authoritative text citations, and a sanction process by courts and/or authorized boards for testimony that is deemed inaccurate, false, or contradictory to the standard of care. PMID- 7778635 TI - Tolerance, patience, forbearance, and charity. PMID- 7778636 TI - A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction. AB - OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 (dinoprostone) gel for preinduction cervical ripening and induction of labor. STUDY DESIGN: One hundred thirty-five patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Fifty microgram tablets of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum of six doses. Prostaglandin E2 in gel form, 0.5 mg, was placed into the endocervix every 6 hours for a maximum of three doses. Medication was not given after either spontaneous rupture of membranes or beginning of active labor. RESULTS: Among 135 patients enrolled, 68 received misoprostol and 67 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (903.3 +/- 482.1 minutes) than in the dinoprostone group (1410.9 +/- 869.1 minutes) (p < 0.001). Oxytocin augmentation of labor occurred more often in the dinoprostone group (65.7%) than in the misoprostol group (33.8%) (p < 0.001). There were no significant differences between routes of delivery. Ten of the misoprostol-treated patients (14.7%) and 13 of the dinoprostone-treated patients (19.4%) had cesarean deliveries. There was a higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (36.7%) than in the dinoprostone group (11.9%) (p < 0.001). However, there were no significant differences in frequency of uterine hyperstimulation or hypertonus. There was a higher prevalence of meconium passage in the misoprostol group (27.9%) than in the dinoprostone group (10.5%) (p < 0.05). There was no significant difference in frequency of abnormal fetal heart rate tracings, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups. CONCLUSIONS: Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor; however when given at this dosage, it is associated with a higher prevalence of tachysystole and meconium passage than is dinoprostone. Further studies to compare the safety of misoprostol to that of dinoprostone and to delineate an optimal dosing regimen for misoprostol are needed. PMID- 7778637 TI - Misoprostol: an effective agent for cervical ripening and labor induction. AB - OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 gel (dinoprostone) for preinduction cervical ripening and induction of labor. STUDY DESIGN: Two hundred seventy-six patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Twenty-five micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours, with a potential maximum of eight doses. Prostaglandin E2 in gel form, 0.5 mg, was placed in the endocervix every 6 hours, with a maximum of three doses. Further medication was withheld with the occurrence of spontaneous rupture of membranes, entry into active phase of labor, or a "prolonged contraction response." RESULTS: Among those evaluated, 138 received misoprostol and 137 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (1323.0 +/- 844.4 minutes) than in the dinoprostone group (1532.4 +/- 706.5 minutes) (p < 0.05). Need for oxytocin augmentation of labor occurred more commonly in the dinoprostone group (72.6%) than in the misoprostol group (45.7%) (p < 0.0001). There were no significant differences in the routes of delivery. Twenty-eight of the misoprostol-treated patients (20.3%) and thirty-eight of the dinoprostone-treated patients (27.7%) required abdominal delivery. Complications such as uterine tachysystole and thick meconium passage occurred with similar frequency in the two treatment groups. CONCLUSIONS: Intravaginal administration of misoprostol appears to be as effective as intracervical dinoprostone for cervical ripening and labor induction. Complications associated with prostaglandin administration were not statistically different between the two treatment groups. The cost of misoprostol ($0.36/100 micrograms) is much less than that of dinoprostone ($75/0.5 mg). PMID- 7778638 TI - Ureteral injury in gynecologic surgery: a ten-year review in a community hospital. AB - OBJECTIVE: Our purpose was to review and analyze ureteral injuries incidental to gynecologic surgery in a community hospital. STUDY DESIGN: During the study period from Jan. 1, 1983, through Dec. 31, 1992, all patient records in which ureteral injury resulted from gynecologic surgery were reviewed. The operative procedure, pathologic result, location of injury, and type of repair were studied. Additionally, the time of recognition and diagnostic methods in these ureteral injuries were analyzed. RESULTS: Nineteen ureteral injuries were incurred during the performance of 4665 gynecologic surgical procedures, an incidence of 0.4%. Patients ranged in age from 23 to 70 years. Recognition of the ureteral injury occurred intraoperatively in 10 patients and was delayed from 1 to 16 days in 9 patients. Six of the ureteral injuries were repaired by end-to end anastomosis, 3 by deligation, and 10 by ureteroneocystostomy. Immediate postoperative urinary integrity was found in all patients. CONCLUSION: Gynecologic surgical procedures in this study resulted in a 0.4% incidence of ureteral injury, and repair of these injuries was successful in all cases for the short term. PMID- 7778639 TI - Satellite in vitro fertilization: the Oregon experience. AB - OBJECTIVE: This study was designed to compare the results of preliminary evaluation, ovarian hyperstimulation, and monitoring of patients at a distant in vitro fertilization satellite center with those treated at the main campus of the program. STUDY DESIGN: Fifty-four patients completing oocyte retrieval cycles at the Eugene satellite Oregon Health Sciences University in vitro fertilization program for the period Jan. 1, 1991, through Dec. 31, 1993, were compared with 222 patients at the main campus for age, peak estradiol level, number of oocytes retrieved, number of embryos, clinical pregnancy rate, and pregnancy outcome. RESULTS: There were no statistically significant differences between the Eugene in vitro fertilization satellite center and the main campus for any of the factors analyzed with the exception of clinical pregnancy rate. The clinical pregnancy rate per cycle at the Eugene satellite center was 39% while the Portland main campus rate was 23% (p = 0.027), presumably because of a larger number of couples with severe male factor infertility at the central site. CONCLUSION: A distant in vitro fertilization satellite program was highly successful in the Oregon experience. In addition to greater convenience to the patients, the program was highly comparable to the main campus program in measured parameter of ovarian hyperstimulation, oocyte retrieval, number of embryos, and pregnancy rate. PMID- 7778640 TI - Do concepts of causes and prevention of cerebral palsy require revision? AB - OBJECTIVE: My purpose was to explore the criteria of The American College of Obstetricians and Gynecologists (Technical Bulletin No. 163) for perinatal asphyxia to be linked to subsequent cerebral palsy. STUDY DESIGN: Analysis of four cases of intrapartum fetal insults with subsequent cerebral palsy and a literature review are presented. RESULTS: All of the four cerebral palsy cases had sufficient intrapartum causes of cerebral palsy, yet none fulfilled The American College of Obstetricians and Gynecologists' linkage criteria. Complications in the cerebral palsy cases were as follows: maternal intrapartum cardiac arrest, fetal skull fracture with brain infarct, intrapartum fetal stroke, and a newborn delivered after uterine rupture with only central nervous system defects. There are no well-done laboratory or clinical studies that unequivocally support the "criteria" that umbilical artery pH must be < 7.00 or the requirements of Apgar score < 3, hypoxic-ischemic encephalopathy, and multiple organ dysfunction. Apparent exceptions to these criteria occur. CONCLUSIONS: The American College of Obstetricians and Gynecologists Technical Bulletin's criteria for cerebral palsy linkage and the role of parturition in cerebral palsy should be reevaluated. A rebirth of obstetric enthusiasm for cerebral palsy research, teaching, and treatment needs to occur. PMID- 7778641 TI - Insulin-like growth factor I promotes leiomyoma cell growth in vitro. AB - OBJECTIVE: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture. STUDY DESIGN: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture. RESULTS: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin like growth factors I but not with insulin-like growth factors II. Neither factor exerted a stimulatory effect on myometrial cells. CONCLUSION: Insulin-like growth factors I preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracrine role in vivo for this factor in conjunction with gonadal steroids in promoting leiomyoma growth. PMID- 7778642 TI - A simplified method of timing frozen embryo transfers. AB - OBJECTIVE: Our purpose was to compare a simple artificial hormone replacement regimen with two other protocols incorporating pituitary down-regulation with gonadotropin-releasing hormone agonist for frozen embryo transfers. STUDY DESIGN: We performed a retrospective analysis of pregnancy outcomes after 366 frozen embryo transfers timed by one of three hormone replacement regimens. The three regimens used were regimen A, leuprolide acetate and transdermal estradiol patches; regimen B, leuprolide acetate and oral micronized estradiol; regimen C, only oral micronized estradiol. RESULTS: The outcomes of 366 consecutive frozen embryo transfers according to one of the three regimens were compared and analyzed. The clinical pregnancy rates were 13.7%, 11.4% and 13.5% in regimens A, B and C, respectively. No statistical differences were found among the three regimens. The mean age of the patients in the three groups was comparable. The mean number of frozen embryos transferred with regimen B was slightly higher, but it did not have a positive impact on the pregnancy rate in this group. CONCLUSION: Controlled sequential hormone replacement results in an endometrium suitable for frozen embryo transfers. Pituitary down-regulation is not necessary. Therefore this regimen is not only more simple to use but also more economical. PMID- 7778643 TI - Spontaneous rupture of the unscarred uterus. AB - OBJECTIVE: By presentation of cases of spontaneous (nontraumatic) ruptures of previously intact uteri, we sought to emphasize important aspects of this rare and dangerous event. STUDY DESIGN: Two case presentations of oxytocin-associated unscarred uterine rupture and review of pertinent literature are used to study risk factors and accompanying clinical characteristics. RESULTS: Both spontaneous ruptures of previous unscarred uteri were associated with low-dose oxytocin augmentation, bradycardia, and uterine hyperstimulation monitor patterns and occurred at the onset of the second stage of labor. CONCLUSION: Because of its rarity, further investigation of spontaneous uterine rupture will depend on case presentations where the associated events listed are noted and uterine hyperstimulation, fetal bradycardia, and second-stage onset are proved or disproved as valid clinical associations. PMID- 7778644 TI - Pulsatile pelvic masses: options for evaluation and management of pelvic arteriovenous malformations. AB - Three recent and previously unreported cases of pelvic arteriovenous malformation are presented. Two were surgically resected in conjunction with elective gynecologic surgery, and the third was embolized by retrograde femoral superselective coaxial catheterization. The causal significance of birth or surgical trauma is discussed, and guidelines for diagnostic angiographic imaging and therapeutic embolization are presented. PMID- 7778645 TI - Comparison of obstetric outcome of a primary-care access clinic staffed by certified nurse-midwives and a private practice group of obstetricians in the same community. AB - OBJECTIVE: The purpose of this study was to compare the obstetric outcome of a primary-care access clinic staffed by certified nurse-midwives, supervised by a private practice group of four obstetricians, with the obstetric outcome of that group's private practice patients. STUDY DESIGN: A retrospective cohort study was performed. Obstetric outcome of 496 clinic patients was compared with that of 611 private patients in the same community from Aug. 1, 1991, to March 31, 1994. RESULTS: Obstetric outcomes as measured by (1) perinatal morbidity and mortality, (2) Apgar score, (3) birth weights, and (4) prematurity rates were comparable between the two groups. Significant was the cesarean section rate of 13.1% (10.5% primary) for the clinic patients and 26.4% (18.5% primary) for the private patients and the high percentage (81.8%) of private patients who elected to have repeat cesarean sections. CONCLUSIONS: (1) Low-income, uninsured, and underinsured women who have access to excellent prenatal care with supervised certified nurse-midwives can have obstetric outcomes similar to women having prenatal care with private obstetricians. (2) Prenatal care with supervised certified nurse-midwives can reduce the cesarean section rate without compromising infant outcome. (3) Utilization of certified nurse-midwives supervised by obstetricians may provide the optimum model for perinatal care, particularly for those women who are at high risk because of social and economic factors and who are currently underserved. PMID- 7778646 TI - Validity of indications for transabdominal cervicoisthmic cerclage for cervical incompetence. AB - OBJECTIVE: Our purpose was to review the indications for transabdominal cervicoisthmic cerclage to determine whether it is a valid alternative to transvaginal cerclage. STUDY DESIGN: A retrospective review of transabdominal cerclage patients at one institution from 1978 to 1994, analysis of the indications for the transabdominal rather than the vaginal approach, and evaluation of fetal outcomes was performed. RESULTS: Twenty-three patients underwent 24 transabdominal cerclages. The primary indication for transabdominal cervicoisthmic cerclage was failed transvaginal cerclage in 14 patients and anatomic unsuitability for transvaginal cerclage in nine. Of the latter, five were a result of diethylstilbestrol exposure and four a result of cervical surgery. All patients were successfully delivered of one or more live babies (total 28, including two sets of twins). Two losses occurred, one after rupture of membranes at 21 weeks on the second pregnancy after cerclage placement and one intraoperative loss with herniation of the membranes. The live birth rate was 93%, compared with 18% salvage of pregnancies beyond the first trimester before the transabdominal cervicoisthmic cerclage procedure. Complications included blood loss requiring transfusion (four patients), although none of these occurred in the last 12 patients. CONCLUSION: We conclude that all the patients had a history compatible with incompetent cervix requiring a cerclage, and none were suitable candidates for a vaginal cerclage. We further conclude that with strict indications transabdominal cervicoisthmic cerclage offers a high rate of fetal salvage with a minimum of complications in patients with extremely poor obstetric histories because of cervical incompetence. PMID- 7778647 TI - HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) presenting as generalized malaise. AB - The syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP) was first described by Weinstein in 1982 and is generally thought to represent a variant of the preeclampsia-eclampsia syndrome. As with other severe manifestations of preeclampsia-eclampsia, epigastric pain and liver tenderness are commonly recognized presenting symptoms of this syndrome, but an underappreciated presenting symptom is generalized malaise or symptoms similar to a flulike syndrome. Two case examples, a review of one private hospital's recent cases, and data contained in the literature are presented to stress the importance of malaise as a presenting complaint during late pregnancy, with recommendations for screening these patients. PMID- 7778648 TI - The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: outcome and toxicity. AB - OBJECTIVE: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer. STUDY DESIGN: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins. RESULTS: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved. CONCLUSION: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall. PMID- 7778649 TI - Endocervical sampling by Kevorkian curette or Pipelle aspiration device: a randomized comparison. AB - OBJECTIVE: Our purpose was to compare two means of endocervical sampling-the Kevorkian curette and the Pipelle aspiration device (Unimar Co., Wilton, Conn.) with respect to patient discomfort, tissue volume, and specimen adequacy for diagnosis. STUDY DESIGN: Fifty-two women undergoing investigation of abnormal cervical cytologic results were assigned randomly to endocervical sampling by Kevorkian or Pipelle instruments. Pain associated with the procedure was assessed by having each subject indicate her pain level on a visual analog scale. Tissue volume was graded by examination of the microscopic slides by two investigators blinded to assignment. Adequacy for diagnosis was evaluated by reviewing pathology reports. RESULTS: Subjects having Pipelle endocervical aspiration (n = 24) had significantly lower mean (+/- SEM) pain scores (27 +/- 5 vs 48.5 +/- 7, p = 0.02) than those in whom the Kevorkian instrument was used (n = 28). However, there were no significant differences in tissue volume obtained or in proportions considered adequate for diagnosis. CONCLUSIONS: Use of the Pipelle instrument was associated with less patient discomfort than Kevorkian curettage for endocervical sampling while providing similar tissue volume and adequacy for diagnosis. PMID- 7778650 TI - Fixation of the vaginal apex to the coccygeus fascia during repair of vaginal vault eversion with enterocele. AB - OBJECTIVE: This study was undertaken to compare the effectiveness of fixation of the vaginal apex to the coccygeus fascia with fixation to the sacrospinous ligament during surgical repair of vaginal vault eversion with enterocele. STUDY DESIGN: The records of 121 patients with posthysterectomy vaginal vault eversion with enterocele treated by the author between 1983 and 1994 were reviewed. Preoperative and postoperative symptoms and findings on pelvic examination and postoperative recovery were compared in patients undergoing sacrospinous ligament suspension and coccygeus fascial suspension. Statistical analysis was performed with chi 2 analysis and Kaplan-Meier life tables. RESULTS: Eighty-one patients underwent fixation to the coccygeus fascia and 30 underwent sacrospinous ligament suspension. The two groups are similar for clinical history, symptoms, and findings on pelvic examination. Ten patients underwent an abdominal sacral colpopexy for specific indications and are not comparable. The incidence of postoperative complications and length of hospital stay were similar for the two vaginal procedures. Patients with coccygeus fascial suspension have a projected 96% cure rate at 2 years compared with an 80% cure rate for patients with a sacrospinous ligament suspension. CONCLUSION: Bilateral vaginal vault suspension to the coccygeus fascia is a safe, simple, and effective technique in the management of vaginal vault eversion with enterocele. PMID- 7778651 TI - Cesarean birth: how to reduce the rate. AB - The cesarean section rate, which approached 25%, has stabilized and started a modest decline. A stated United States national goal by the year 2000 is a rate of 15%. Suggested rates are 12% for primary and 3% for repeat cesarean sections. The major indications for cesarean section are prior cesarean delivery (8%), dystocia (7%), breech presentation (4%), fetal distress (2% to 3%), and others. The major areas of reduction must occur in the categories of prior cesarean delivery and dystocia. An expanded use of trial of labor and vaginal birth after a prior cesarean section will produce further reductions. Countries in Europe achieve > 50% vaginal birth after a prior cesarean section compared with 25% in the United States. A heightened awareness must occur regarding the decision to perform the first cesarean section. The residual impact, a scarred uterus, affects 12% to 14% of women seen for delivery. Even if 50% achieve a vaginal birth after a prior cesarean section, the national goals are unachievable. The obstetrician must consciously consider the impact of "once a cesarean, always a scar." PMID- 7778652 TI - Virilizing adrenal carcinoma in a woman of reproductive age: a case presentation and literature review. AB - Virilizing adrenal carcinoma is a rare disease, especially in women of reproductive age. A young woman who was seen with hirsutism, virilization, and infertility had a well-differentiated adrenal cortical carcinoma. After treatment she conceived twice and currently is disease free 8 years after treatment. This case illustrates that adrenal carcinoma and its treatment need not eliminate a woman's reproductive potential. PMID- 7778653 TI - Management of term breech presentation: a protocol of external cephalic version and selective trial of labor. AB - OBJECTIVE: The results of a program of external version and selective trial of labor for term breech presentation are reviewed. This is a follow-up to our 1987 report describing management of singleton, term breech presentations and expands our 16-year experience to 1180 cases. STUDY DESIGN: All term breech presentations cared for in 1985 through 1992 are reviewed and outcome contrasted with those predicted in our earlier report. During these 8 years a trial of external version was offered if a breech presentation was identified after 36 completed weeks' gestation and before active labor. The criteria for allowing a trial of labor are detailed. RESULTS: Four hundred sixty-four breech presentations were identified for review. Three hundred eighty-two (82%) were diagnosed before active labor. Of these, 344 (90%) underwent an attempt at external version, of which 174 (51%) were successful. The 290 breech presentations where version either was not attempted or was unsuccessful were stratified into three groups: cesarean section without labor (147), trial of labor with cesarean section (90), and trial of labor with vaginal delivery (53). The 174 cases where version was successful were stratified into two additional groups on the basis of the eventual route of delivery. Careful review of maternal and fetal variables indicates that a trial of labor in selected patients resulted in vaginal delivery in only 37% but was achieved without an increase in fetal or maternal mortality or morbidity. Surprisingly, 54 of the 174 cases where version was successful were ultimately delivered by cesarean section. This 31% rate of cesarean delivery is significantly higher than the 15% rate observed for all cases of term, singleton vertex presentation. A higher prevalence of cases complicated by failed progress in labor and failed induction contributed to the excess. CONCLUSION: External version is successful in 51% of cases of term breech presentation. With careful selection, cases where version has failed can be allowed to labor and be delivered vaginally. The incidence of cesarean section (31%) for those cases where version had been successful was surprisingly high, largely because of an increase in labor abnormalities and failed labor inductions. PMID- 7778654 TI - Endovaginal ultrasonographically guided transvaginal drainage for treatment of pelvic abscesses. AB - OBJECTIVE: This study assessed the ability of endovaginal ultrasonographically directed transvaginal drainage of pelvic abscesses to treat patients who failed intravenous antibiotic therapies and whose abscesses were not amenable to percutaneous or colpotomy drainage. STUDY DESIGN: Thirty-one women who would otherwise have required surgery to treat their pelvic abscesses underwent the procedure. Immediate clinical response and longer-term follow-up results were collected retrospectively. RESULTS: Thirty-four procedures were performed on 31 women. Purulent material (10 to 350 ml) was aspirated in every case. Twenty-six of the 31 women (84%) were successfully treated by drainage. In the 6- to 21 month follow-up period, 10 women remained without problems, eight had sequelae related to pelvic infection, and eight were lost to follow-up. CONCLUSION: Endovaginal ultrasonographically guided transvaginal drainage is a safe, effective procedure for treatment of pelvic abscesses and should be considered the route of choice for draining collections not amenable to percutaneous or colpotomy drainage. PMID- 7778655 TI - On the treatment of vesico-vaginal fistula. PMID- 7778656 TI - Pregnancy in an anephric woman. PMID- 7778658 TI - Cerebral arterial-umbilical cord arterial systolic/diastolic ratios: an independent predictor of poor neonatal outcome. PMID- 7778657 TI - Effects of maternal inhalation of 40% oxygen on fetal oxygen saturation. PMID- 7778659 TI - Vascular anatomy of the anterior abdominal wall in gynecology and obstetrics. PMID- 7778660 TI - A vasoactive drug as a risk to pregnancy outcome. PMID- 7778661 TI - Evaluation of stress during labor and parturition. PMID- 7778662 TI - Are low-dose oral contraceptives safer and better? PMID- 7778663 TI - Low-dose oral contraceptives are safer than high-dose pills. PMID- 7778664 TI - Rectal bleeding complicating radiofrequency-induced thermal destruction of the endometrium. PMID- 7778665 TI - Preventing mother-to-child transmission of human immunodeficiency virus infection. PMID- 7778666 TI - Ultrasonographic diagnosis of "cervical incompetence". PMID- 7778667 TI - The role of patient mobilization after embryo transfer in in vitro fertilization programs. PMID- 7778668 TI - The American Board of Obstetrics and Gynecology, Inc. PMID- 7778670 TI - Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. AB - The mcl-1 gene encodes an approximately 37-kd protein that has significant homology with Bcl-2, an inhibitor of programmed cell death that is expressed in many types of long-lived cells. In this study we determined the in vivo patterns of Mcl-1 protein production in normal human tissues by immunohistochemical means, using specific polyclonal antisera, and made comparisons with Bcl-2. Like Bcl-2, Mcl-1 immunostaining was observed in epithelial cells in a variety of tissues, including prostate, breast, endometrium, epidermis, stomach, intestine, colon, and respiratory tract. However, often the expression of mcl-1 and bcl-2 in complex epithelia occurred in gradients with opposing directions, such that Bcl-2 immunostaining tended to be higher in the less differentiated cells lining the basement membrane, whereas Mcl-1 immunostaining was more intense in the differentiated cells located in the upper layers of these epithelia. The in vivo patterns of mcl-1 and bcl-2 expression were also strikingly different in several other tissues as well. Within the secondary follicles of lymph nodes and tonsils, for example, germinal center lymphocytes were Mcl-1 positive but mostly lacked Bcl-2; whereas mantle zone lymphocytes expressed bcl-2 but not mcl-1. Intense Mcl 1 immunoreactivity was also detected in several types of neuroendocrine cells, including the adrenal cortical cells that are Bcl-2 negative, sympathetic neurons that also contain Bcl-2, a subpopulation of cells in the pancreatic islets, Leydig cells of the testis, and granulosa lutein cells of the ovarian corpus luteum but not in thyroid epithelium, which is strongly Bcl-2 positive. Little or no Mcl-1 was detected in neurons in the brain and spinal cord, in contrast to Bcl 2, which is present in several types of central nervous system neurons. Conversely, strong Mcl-1 immunostaining was found in cardiac and skeletal muscle, which contain comparatively less Bcl-2. Additional types of cells that are Bcl-2 negative but that expressed mcl-1 include chondrocytes and hepatocytes. These findings demonstrate that mcl-1 expression is widespread in vivo and imply that the Mcl-1 and Bcl-2 proteins fulfill different roles in the overall physiology of cell death regulation. PMID- 7778671 TI - Acetylcholine receptor alpha-subunit and myogenin mRNAs in thymus and thymomas. AB - Myasthenia gravis is an autoimmune disorder characterized in most cases by serological antibody against the acetylcholine receptor (AChR). Evidence for intrathymic localization of AChR suggests that the thymus has an important role in the pathogenesis of this disorder. Using reverse transcription followed by the polymerase chain reaction, we have demonstrated AChR alpha-subunit mRNA in thymuses and thymomas from patients with and without myasthenia gravis. We have also studied the expression of myogenin which is known to be involved in the regulation of AChR expression. By using the reverse transcription polymerase chain reaction, we found myogenin mRNAs in all of the thymuses and thymomas. Thus, both AChR alpha-subunit and myogenin mRNA are present in all of these specimens. By immunohistochemistry myoid cells (desmin and myoglobin positive) were present in all (four of four) thymuses studied and in two of five thymomas. Thus, in thymomas, nonmyoid cells might express both AChR and myogenin. These results indicate that cells within the thymus and thymoma express AChR and its regulatory protein myogenin and that such cells, under certain conditions, might play a role in the triggering of myasthenia gravis. PMID- 7778672 TI - DNA fragmentation of human infarcted myocardial cells demonstrated by the nick end labeling method and DNA agarose gel electrophoresis. AB - Myocardial tissue taken from 19 autopsy cases of myocardial infarction were examined both by the nick and labeling method (NELM) and by DNA agarose gel electrophoresis in order to demonstrate the localization of cells with fragmented DNA and to confirm the internucleosomal cleavage of DNA biochemically. The nuclei corresponding to those with the histological features of acute myocardial infarction in hematoxylin and eosin (H&E)-stained sections were stained strongly positive with the nick end labeling method. Myocardial cells corresponding to those with nick end labeling method-stained nuclei, on the other hand, had mostly pyknotic and karyolytic nuclei and some unremarkable nuclei, even nuclear ghosts, and showed degenerated cytoplasm, including contraction band necrosis in H&E stained preparations. The agarose gel electrophoresis of DNA extracted from the corresponding areas mentioned above showed the ladder pattern of internucleosomal cleavage characteristic of apoptosis. The present study revealed that infarcted myocardial cells with nuclear outlines, even nuclear ghosts, showed a distinct DNA fragmentation with the ladder pattern of internucleosomal cleavage. It is concluded from this study that the damaged myocardial cells of acute myocardial infarction represent a coagulation necrosis having the biochemical nature of apoptosis. PMID- 7778673 TI - Correlation of microscopic phenotype with genotype in a formalin-fixed, paraffin embedded testicular germ cell tumor with universal DNA amplification, comparative genomic hybridization, and interphase cytogenetics. AB - We present a strategy for the evaluation of numerical copy number changes of DNA segments within a solid tumor genome that allows the correlation of microscopic phenotype with genotype in formalin-fixed, paraffin-embedded tumor material. Cells from a human testicular germ cell tumor and adjacent tissue areas with normal seminiferous tubules were selected separately from microscopically analyzed histological tissue sections, and DNA was extracted from the selected areas. After universal DNA amplification, the amplification products were subjected to comparative genomic hybridization. The results confirmed balanced chromosome copy numbers for the normal tissue area, although the analysis of the tumor tissue area revealed numerous gains and losses of chromosome segments. The comparative genomic hybridization results were used to select DNA probes for interphase cytogenetics on serial sections. We conclude that this technique allows the screening of selected tissue areas for numerical DNA alterations, thus enabling a direct phenotype-genotype comparison. PMID- 7778669 TI - Chemokines and tissue injury. AB - Accumulation of leukocytes at sites of inflammation is essential for host defense, yet secretory products of the white cells may augment injury by damaging surrounding healthy tissues. Members of the chemokine family of chemotactic cytokines play a fundamental role in this process by attracting and stimulating specific subsets of leukocytes. In vitro studies suggest that chemokines participate in at least three phases of leukocyte recruitment. First, they foster tight adhesion of circulating leukocytes to the vascular endothelium by activating leukocytic integrins. Second, because of their chemoattractant properties, chemokines guide leukocytes through the endothelial junctions and underlying tissue to the inflammatory focus. Finally, chemokines activate effector functions of leukocytes, including production of reactive oxygen intermediates and exocytosis of degradative enzymes. Animal studies in which antibodies are used to neutralize the activity of individual members of the chemokine family confirm that these mediators contribute to the development of both acute and chronic inflammatory conditions. A number of mechanisms may operate in vivo to limit the proinflammatory properties of chemokines. Therapies that target chemokines directly or enhance the body's mechanisms for controlling their activity may prove to be reasonable approaches for treatment of inflammatory diseases. PMID- 7778674 TI - Detection of chromosomal imbalances in transitional cell carcinoma of the bladder by comparative genomic hybridization. AB - Comparative genomic hybridization (CGH) was applied for a comprehensive screening of chromosomal aberrations in 14 transitional cell carcinomas of the bladder of different grade and stage. The results were compared in a number of selected cases with those obtained by restriction fragment length polymorphism analyses and targeted fluorescence in situ hybridization. Distinct amplifications, found with CGH, were located on 3p22-24, 10p13-14, 12q13-15, 17q22-23, 18p11, and 22q11 13. These high copy number amplifications and the frequency of imbalances involving chromosome 5, occurring in 4 of 14 cases, have not yet been identified in transitional cell carcinomas. Apart from these new aberrations, imbalances were detected in 3 or more cases for chromosomes 9 and 11, as already described previously in the literature. In four tumors, the copy number of specific chromosomal regions was also analyzed by interphase cytogenetics. Although in most instances the CGH data were confirmed, in one tumor, distinct differences were observed, possibly a result of heterogeneity of the tumor cell population. Furthermore, the CGH data were compared with loss of heterozygosity as revealed by restriction fragment length polymorphism analysis in the same tumors. In 80% of informative cases, no loss was detected by restriction fragment length polymorphism or by CGH. Of the 15 cases of loss of heterozygosity, 7 showed a loss also with CGH, whereas in 8 cases no loss was observed. In summary, CGH is a fast method to obtain a comprehensive picture of chromosomal imbalances in transitional cell carcinomas, including a number of previously unknown genomic alterations such as high level amplifications. PMID- 7778675 TI - Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia. AB - Nasopharyngeal carcinoma (NPC) samples of distinct histological types, including squamous cell carcinoma (WHO type 1), nonkeratinizing carcinoma (WHO type 2), and undifferentiated carcinoma (WHO type 3), were analyzed for Epstein-Barr virus (EBV) infection and gene expression by using in situ and biochemical techniques. The EBV-encoded RNAs (EBER) were detected in situ in most tumor cells of all three WHO types of NPC. In foci of squamous differentiation and keratinization within less differentiated NPC and throughout the expanse of well differentiated squamous cell carcinoma, EBER expression was less abundant. Latent membrane protein, an EBV-encoded membrane protein, was detected in 72% (36/50) of all NPC and 67% (6/9) of the cases of squamous cell carcinoma. The EBV genomes were present as clonal episomal forms, without detectable linear viral DNA, in all cases of squamous cell carcinoma analyzed. Polymerase chain reaction amplification of cDNA detected EBV transcription for Epstein-Barr nuclear antigen 1, latent membrane proteins 1 and 2, and BamHI A in all samples, indicating that all forms of NPC express the same EBV genes. These results reveal that EBER expression is significantly decreased in areas with squamous differentiation and confirm that all types of NPC, regardless of histological type or differentiation contain clonal episomal EBV genomes, express specific EBV genes and are a clonal expansion of EBV-infected cells. PMID- 7778676 TI - Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors. AB - Major differences in the long-term clinical response to castration therapy of prostatic carcinoma suggests intertumoral differences in cellular response and defines a need for identification of patients with an eventually positive outcome as well as those in need of additional treatment. Using morphometry, monoclonal antibodies against Bcl-2, c-myc, Ki-67, and p53 proteins, and an in situ method to visualize apoptotic cells, we examined the short-term response of prostatic tumors to castration in core biopsies from 18 prostatic cancer patients taken the day before and 7 days after castration. At the histological level, 3 tumors seemed practically unaffected by castration. In 15 tumors, castration induced vacuolization of tumor cell cytoplasm and decreases in nuclear area and Ki-67 index. In these 15 tumors, apoptotic index was significantly increased in 6, principally unaffected in 6, and decreased in 3. The 6 tumors responding with an increase in apoptotic index were WHO grade 1 or 2 and negative for p53, c-myc, and Bcl-2 or contained only few Bcl-2- or c-myc-positive tumor cells before therapy. The 12 tumors in which apoptotic index was unaffected or decreased were WHO grade 2 or 3 and immunopositive for one or more of p53, Bcl-2, and c-myc proteins before therapy. The Bcl-2 index was significantly increased in 10 patients. Prostatic tumors may respond in a variety of possibly predictable ways to castration therapy including a decrease in apoptotic index. The magnitude of these responses are not correlated in individual tumors, suggesting that the common classification of prostatic tumors as either androgen dependent (dying after castration) or independent (not responding at all to castration) may be an oversimplification. PMID- 7778677 TI - Dynamics of cell proliferation and cell death during the emergence of primitive neuroectodermal tumors of the immature central nervous system in transgenic mice. AB - Cell proliferation and cell death play critical roles in embryonic development, postnatal tissue maintenance, and tumor formation. To understand the interplay between cell proliferation and death in tumor formation, we studied these two processes in nascent primitive neuroectodermal tumors that arose postnatally from neuroepithelial cells ventral to the median eminence of transgenic mice (designated rTH-Tag mice) carrying a Simian virus 40 large T antigen transgene driven by a rat tyrosine hydroxylase promoter. Cell proliferation continued in the neuroepithelium of the ventral median eminence in wild-type and transgenic animals for the first 2 weeks of postnatal life but subsided completely in the wild-type mice after 2 weeks of age. In contrast, mitotic activity persisted in these progenitor cells of the rTH-Tag mice, and there was a dramatic increase in mitotic activity after 10 weeks leading to the formation of primitive neuroectodermal tumors despite sustained cell death activity. We conclude that primitive neuroectodermal tumors originate from progenitor cells in the ventral median eminence of rTH-Tag mice in early postnatal life when progenitors fail to respond to signals to exit the cell cycle. Thus, the disruption of mechanisms that regulate cell proliferation and cell death in the developing brain may underlie the emergence of primitive neuroectodermal tumors in the rTH-Tag mice. PMID- 7778679 TI - Expression of cell adhesion molecules on liver-associated lymphocytes and their ligands on sinusoidal lining cells in patients with benign or malignant liver disease. AB - Liver sinusoids, in contrast with the capillaries of other tissues, contain large numbers of sequestered lymphocytes. These blood-borne cells preferentially home in the liver. The mechanism regulating the recruitment of these cells and molecular regulation of the recognition of endothelial cells is as yet unclear. The present study sought to evaluate the cell adhesion molecules on human liver associated lymphocytes and their ligands on sinusoidal lining cells in 29 patients undergoing partial hepatectomy for liver tumors. Liver-associated lymphocytes and peripheral blood lymphocytes were analyzed by flow cytometry using monoclonal antibodies. Frozen sections of liver tissue were stained according to alkaline phosphatase anti-alkaline phosphatase method. Cytometric analysis showed that virtually all liver-associated lymphocytes expressed on their surface the cell adhesion molecules LFA-1 and VLA-4. This liver-associated lymphocyte population also presented a significantly higher percentage of Mac 1, ICAM-1, and LFA-3 and an increased surface expression of LFA-1, LFA-2, and NCAM in comparison with peripheral blood lymphocytes. It was likewise shown that sinusoidal cells express ICAM-1, ICAM-2, ICAM-3, VCAM-1 and LFA-3 ligands. Liver associated lymphocytes thus strongly express a number of different adhesion molecules. The corresponding ligands were also detected on sinusoidal lining cells. LFA-1 and VLA-4 would seem to be important pathways of temporary lymphocyte-endothelial adhesion in liver sinusoids. PMID- 7778678 TI - Widespread cytoskeletal pathology characterizes corticobasal degeneration. AB - Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized to Leu 7-expressing oligodendrocytes. In addition, a wide array of neuronal pathology is defined with tau-positive inclusions in multiple domains of a variety of cortical neurons. CBD thus exhibits widespread glial and neuronal cytoskeletal pathology, including a novel structure, the astrocytic plaque. CBD is a disease of generalized cytoskeletal disruption affecting several cell types and multiple domains of these cells. The further definition of CBD pathology refines the diagnosis and pathophysiological understanding of this unique disease and has important implications for other neurodegenerative diseases, like Alzheimer's disease, characterized by abnormal tau deposition. PMID- 7778680 TI - Abnormal morphology of fibrillin microfibrils in fibroblast cultures from patients with neonatal Marfan syndrome. AB - The Marfan syndrome (MFS) is a connective tissue disorder manifested by variable and pleiotropic features in the skeletal, ocular, and cardiovascular systems. The average life span in MFS is about 35 years. A group with much more severe cardiovascular disease and a mean life span of approximately 1 year also exists. We refer to this latter group as "neonatal Marfan syndrome" (nMFS). Fibrillin defects are now known to be the cause of MFS and nMFS. Immunofluorescence studies were the first to demonstrate this association. Here we describe immunofluorescence studies in a series of 10 neonates and summarize their salient clinical features. In vitro accumulation of fibrillin reactive fibers was assayed using monoclonal antibodies to fibrillin in hyperconfluent fibroblast cultures. As was previously observed in MFS, fibroblast cultures from nMFS patients showed an apparent decrease in accumulation of immunostainable fibrillin. Significantly, however, the morphology of the immunostained fibrils in the nMFS cultures were abnormal and differed not only from control cultures, but also from those seen in cultures of MFS fibroblasts. The nMFS fibrils appeared short, fragmented, and frayed, characteristics that are not seen in MFS. Both the clinical and fibrillin morphology data provide evidence to suggest a useful subclassification of nMFS in the spectrum of MFS. PMID- 7778681 TI - Anion exchanger immunoreactivity in human salivary glands in health and Sjogren's syndrome. AB - Salivary gland ducts play a relevant role in saliva secretion through transport processes. Na(+)-independent chloride-bicarbonate anion exchangers (AE) may be involved in these processes by generating ion fluxes into the salivary secretion. In Sjogren's syndrome, a disorder with gland dysfunction, there might be an impaired expression of AE proteins. Here we study AE immunoreactivities in human salivary glands, both in health and in Sjogren's syndrome. Immunohistochemistry was carried out on salivary glands from normal subjects and patients with Sjogren's syndrome, using two monoclonal antibodies against AE1 and AE2. Normal salivary glands showed AE2 immunoreactivity, which was restricted to the epithelium of the ducts, with no staining at the acini. A strong positivity was seen in the basolateral portion of the striated ducts, while interlobular duct cells showed a discrete positivity at their apical pole. In salivary glands from most of the patients with Sjogren's syndrome, AE2 immunoreactivity was absent in the ducts as well as in the acini. In both normal and diseased salivary glands, AE1 immunoreactivity was only located at the erythrocyte membrane. The recently reported AE0 was discarded because no AE0 message was found in salivary glands by reverse transcription polymerase chain reaction. In conclusion, AE2 immunoreactivity is observed in the ducts of normal salivary glands, particularly in the striated ducts. AE2 immunoreactivity is virtually absent in salivary glands from patients with Sjogren's syndrome, which may reflect either a loss of AE2 after inflammatory atrophy, or a primary defect occurring in the disease. PMID- 7778682 TI - Immunopathology of chronic lentivirus-induced arthritis. AB - This study evaluated histopathology and mononuclear cell phenotypes in synovial lesions of chronic arthritis induced by experimental infection of Saanen goats with caprine arthritis-encephalitis lentivirus. Histological examination of carpal joint synovium of three infected goats with clinical arthritis revealed progressive lesions consisting of membrane villus hypertrophy with extensive angiogenesis and mononuclear cell infiltration and degenerative changes of membrane villus necrosis associated with loss of vasculature and infiltrates. Changes in synovial tissue of five age-matched infected goats without clinical arthritis were limited to moderate synovial membrane hyperplasia also noted in an age-matched uninfected goat. Immunohistochemistry identified CD45R+ CD5- B lymphocytes as the principal component of most perivascular infiltrates in arthritic synovium. Other mononuclear cells included perivascular CD4+ and CD8+ T lymphocytes and macrophages with a prominent accumulation of CD8+ T lymphocytes at the lining surface of inflamed villi. T lymphocytes and macrophages as well as synovial lining cells were activated with respect to MHC class II but not for interleukin-2 receptors. Inflamed villi also contained lymphoid aggregates comprised of B cell germinal centers and activated T-cell mantles. B cells expressing immunoglobulin occurred around follicles and throughout inflamed villi. These findings indicate that memory immune responses that favor expansion and maturation of B cells and immunoglobulin production contribute to the immunopathology of chronic arthritis. PMID- 7778684 TI - Early and persistent up-regulated expression of renal cortical osteopontin in experimental hydronephrosis. AB - The mechanical disturbance after unilateral ureteral obstruction (UUO) is a nonimmune stimulus that is capable of eliciting a florid macrophage infiltration of the kidney and subsequent post-inflammatory renal scarring. Osteopontin has potential chemoattractant activity and, for this reason, we delineated the kinetics of its expression in the renal cortex of rats with UUO. Whole body X irradiation and reversal of UUO were utilized as interventional maneuvers to give additional pathobiological insight into this protein's role in the response of the kidneys to ureteral obstruction. Increased osteopontin mRNA levels in obstructed kidneys versus contralateral unobstructed specimens were evident as early as 4 hours after UUO and steadily increased at 12, 24, 48, and 96 hours after UUO. Both X-irradiation and reversal of UUO failed to significantly modulate renal cortical osteopontin mRNA expression at all of the above time points. Paralleling the increments in renal cortical osteopontin mRNA levels were significant elevations in the cortical renal interstitial macrophage number, which was significantly diminished by previous X-irradiation but not reversal of UUO. Focal labeling of osteopontin was noted in both tubular and Bowman's capsular epithelium in obstructed kidneys as early as 4 hours after UUO, whereas, in the contralateral unobstructed specimens, there was only faint staining in Bowman's capsule. By 96 hours after UUO, obstructed kidneys exhibited intense, diffuse staining for osteopontin in both tubules and Bowman's capsule. Osteopontin's immunolocalization was not modulated by X-irradiation or reversal of UUO. These data support the contention that osteopontin is involved in the accumulation of macrophages within the peritubular and periglomerular interstitium in the obstructed renal cortex. PMID- 7778683 TI - Tumor necrosis factor-alpha is expressed by glomerular visceral epithelial cells in human membranous nephropathy. AB - The role of tumor necrosis factor alpha (TNF-alpha) was examined in biopsy-proven glomerulonephritis by immunohistochemistry, in situ hybridization, immunogold electron microscopy, immunoassay in serum and urine, and urinary immunoblot. Striking glomerular capillary wall and visceral glomerular epithelial cell TNF alpha protein staining was observed in all cases of membranous nephropathy and membranous lupus nephropathy. Staining was less frequently observed in crescentic glomerulonephritis and in isolated cases of other histological subtypes of glomerulonephritis, usually in association with glomerular macrophages. By immunogold electron microscopy TNF-alpha was localized in membranous nephropathy within the visceral glomerular epithelial cells, and also in the glomerular basement membrane, especially in relation to immune deposits. In situ hybridization localized TNF-alpha mRNA exclusively to glomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations of TNF-alpha were significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulonephritis. The expression of TNF-alpha by glomerular epithelial cells exclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of membranous nephropathy. PMID- 7778685 TI - Autoantibodies to the laminin P1 fragment in HgCl2-induced membranous glomerulopathy. AB - Exposure to mercuric chloride induces the development of a membranous glomerulopathy with high proteinuria in DZB rats, in which immunoglobulin (Ig)G1 and IgG2a bound in the glomeruli were previously found to react with laminin of the EHS tumor and several unidentified glomerular basement membrane components. Monoclonal antibodies were prepared by fusing cervical and mandibular lymph node cells from a HgCl2-treated DZB rat with a nonsecreting mouse myeloma. Monoclonal antibodies were screened for reactivity with collagenase-digested glomerular basement membrane and kidney sections; upon subcloning, eight stable hybridomas were obtained, named MEC1 to MEC8. MEC2 (IgG1, kappa), MEC3 (IgM, kappa), and MEC5 (IgG1, kappa), as well as the polyclonal glomerular eluate, reacted preferentially with the P1 fragment of the laminin-1 (alpha 1 beta 1 gamma 1) isoform. MEC8 (IgM, kappa) reacted with the P1 and the E4 fragment of laminin. Both MEC6 (IgM, kappa) and MEC8 bound to actin and to various other, unidentified cellular antigens, indicating that MEC6 and MEC8 are polyreactive antibodies. MEC7 (IgM, kappa) bound to a cytoskeleton-linked cell membrane antigen, present on various epithelial cells and between heart muscle fibers and associated with small peripheral, intramuscular nerves. Several of the MEC monoclonal antibodies bound in vivo along the glomerular capillary wall. Although discrete electron dense subepithelial immune aggregates were not detected and proteinuria was not induced, MEC3 localization changed from a continuous pattern into a fine granular pattern along the glomerular basement membrane, and focally along the TBM, upon passive transfer into naive DZB rats. These findings suggest a pathogenetic role for the P1 fragment of laminin either in the induction phase of HgCl2-induced membranous glomerulopathy as an immunogen or in the effector phase as a target antigen. PMID- 7778686 TI - Transcription and translation of gp600 and receptor-associated protein (RAP) in active Heymann nephritis. AB - Active Heymann nephritis (HN) of rat, an autoimmune glomerular disease, is a model for human membranous glomerulonephropathy. The autoantigen of HN is a glycoprotein of approximately 600 kd that is present in both rat and human kidneys. Another kidney protein of 39-45 kd called receptor-associated protein (RAP) is associated with gp600. In normal kidney very little gp600 and RAP can be detected in glomeruli. This study was undertaken to determine whether the synthesis of gp600 and RAP would increase after development of active HN. Kidneys from normal (n = 5) and active (n = 11) HN rats were studied for expression of gp600 and RAP and their mRNAs by immunofluorescence and in situ hybridization. In all HN kidneys in contrast to normal kidneys both the transcription and translation of gp600 were markedly increased in glomeruli and proximal tubules. Transcription and translation of RAP were also increased but less so than gp600. The site of increased transcription of gp600 and RAP in glomeruli was clearly localized to the visceral glomerular epithelial cells. CONCLUSIONS: This is the first study to show increased transcription of gp600 and RAP in active HN and the first study to identify the visceral glomerular epithelial cell as the cell for the increased transcription. PMID- 7778687 TI - Platelet-derived growth factor ligand and receptor expression by large vessel endothelium in vivo. AB - Using an injury model of the rat carotid artery and aorta, we have determined the time course of expression for PDGF ligands and receptors in endothelium by in situ hybridization and immunostaining. Platelet-derived growth factor (PDGF)-A and -B chains-were expressed in endothelial cells at the wound edge, but no expression was detectable in uninjured endothelium. PDGF-alpha receptor was expressed in a similar pattern as PDGF-A chain whereas expression of PDGF-beta receptor was not detected at any time. Expression of PDGF-B chain did not correlate with endothelial cell replication and a neutralizing antibody against PDGF-B had no effect on endothelial regrowth in the denuded aorta. Intimal smooth muscle cells are known to express PDGF-beta receptors and could thus be stimulated to migrate in response to PDGF-B from endothelial cells. PMID- 7778688 TI - Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue. AB - The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. PMID- 7778690 TI - Inhibition of parathyroid hormone-related protein release by extracellular calcium in dispersed cells from human parathyroid hyperplasia secondary to chronic renal failure and adenoma. AB - The relationship between parathyroid hormone-related protein (PTHrP) release from parathyroid cells and extracellular calcium ion concentration was investigated in three cases of parathyroid hyperplasia secondary to chronic renal failure and in four cases of parathyroid adenoma. Amounts of PTHrP released from individual parathyroid cells dispersed from surgical specimens were estimated by cell immunoblot assay. Parathyroid cells from both hyperplasias and adenomas showed significant suppression in the release of PTHrP with increase in extracellular calcium ions, but the amounts of PTHrP released from adenoma cells were significantly larger than from hyperplasia cells. The maximal value for PTHrP released within 120 minutes from adenoma cells was 2.91 +/- 2.11 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 1.32 +/- 0.35 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). On the other hand, the maximal value for PTHrP released from hyperplasia cells was 1.79 +/- 1.56 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 0.32 +/- 0.19 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). These results demonstrate actual release of PTHrP from abnormal parathyroid tissues into the extracellular space with the response to extracellular calcium ions depending on the cell status. Given the lack of definite histological criteria to differentiate between hyperplasias and adenomas in the parathyroid gland, the presently demonstrated significant difference in the ability to release PTHrP is important in pointing to parathyroid hyperplasia secondary to chronic renal failure as a distinct pathological entity separate from parathyroid adenoma. PMID- 7778691 TI - Mammalian tyrosinase-related protein-1 is recognized by autoantibodies from vitiliginous Smyth chickens. An avian model for human vitiligo. AB - The Smyth line (SL) chicken is an animal model for the human acquired depigmentary disorder vitiligo. Affected birds from this line express a postnatal loss of melanocytes in feather and ocular tissues. This vitiligo-like depigmentation is considered to be a disorder with two interacting components: melanocyte dysfunctions and autoimmune reactions. Previously, SL chicks were shown to express high levels of circulating autoantibodies that bind to chicken melanocyte proteins with molecular masses between 65 and 80 kd. Three mammalian melanocyte proteins known to have isoforms in this molecular mass range are tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2. Of these, only tyrosinase is reported to be expressed in chicken melanocytes. The results presented in this study indicate that, of these three candidate proteins, TRP-1 is the primary antigen recognized by the SL autoantibodies. SL autoantibodies recognize a chicken melanocyte protein that is different from that of tyrosinase or the candidate chicken TRP-2. In addition, several types of experiments incriminate TRP-1 as the primary mammalian melanocyte antigen recognized by SL autoantibodies. We further verified that chicken melanocytes expressed messages for TRP-1 by finding positive signals on Northern blots of chicken melanocyte RNA probed with mammalian TRP-1 cDNA fragments. Therefore, we conclude from these results that the SL autoantibodies primarily recognize TRP-1 in mammalian melanocytes and suggest that chicken melanocytes express a homologue of TRP-1 (the human gp75 and the murine brown/b locus protein). PMID- 7778694 TI - In pursuit of excellence. PMID- 7778689 TI - Characterization and functional studies on rat liver fat-storing cell line and freshly isolated hepatocyte coculture system. AB - We developed and characterized a coculture system composed of a fat-storing cell clone (CFSC-2G) and freshly isolated hepatocytes that can reproduce in vitro some of the physical and functional relationships observed in vivo. Hepatocytes in the coculture are polarized, are smaller in size than hepatocytes plated on plastic, maintain a cuboidal shape, and have a tendency to form cords. Fat-storing cells, which are initially extended, retract and leave spaces that resemble liver sinusoids. Both cell types in the coculture system are functional for at least two weeks as determined by the expression of high levels of liver-specific protein mRNAs as well as by the production and secretion of liver-specific proteins into the culture medium. The hepatocytes maintain relatively high levels of asialoglycoprotein receptor on their cell surface and form functional gap junctional complexes with fat-storing cells. Hence, this coculture system retains a number of differentiated functions of hepatocytes, making it a useful model to study cell-cell interactions in culture and to analyze regulation of hepatocyte functions. PMID- 7778693 TI - Rodent model of reproductive tract leiomyomata. Clinical and pathological features. AB - Mesenchymal tumors of the lower reproductive tract of women are poorly understood at the molecular level as a result in part of the lack of relevant animal models. The present study describes a novel model of gynecological smooth muscle tumors in which these neoplasms arise in Eker rats as part of a familial cancer syndrome. The tumors develop as a result of a germline mutation in the tuberous sclerosis 2 (TSC2) gene, and predisposition to tumor development is inherited in an autosomal dominant fashion. Uterine and/or cervical tumors arise spontaneously as single or multicentric neoplasms and increase in incidence with increasing age. The tumors were classified into three phenotypic variants of leiomyoma/leiomyosarcoma and into stromal cervicovaginal tumors on the basis of cytological and histological features and immunostaining patterns for smooth muscle actin and desmin. Tumors histologically identical to the typical human myometrial leiomyoma arose, as did a subset of atypical leiomyomas having an epithelioid phenotype. Eker rats were found to develop both benign and malignant smooth muscle tumors. The high spontaneous incidence of smooth muscle tumors of uterus and cervix in this rodent model provides a unique opportunity to study the molecular mechanisms underlying the development of these clinically important gynecological neoplasms. PMID- 7778692 TI - Presence of CD3+CD8+Bcl-2(low) lymphocytes undergoing apoptosis and activated macrophages in lymph nodes of HIV-1+ patients. AB - Infection with human immunodeficiency virus 1 causes profound changes in the lymph nodes of infected patients. In particular, large numbers of CD8+CD45RO+ T cells infiltrate both the paracortex and the germinal centers. These cells contained the cytotoxic granule-associated protein TIA-1 but showed no detectable levels of perforin and shared the same characteristics of the expanded, activated, short-lived CD8+ population found during acute viral infections. These cells expressed low levels of Bcl-2 and are likely to be short-lived in vivo as evidenced by the direct observation of CD8+ apoptotic cells in the paracortical areas of the infected nodes. Changes in the paracortical nonlymphoid populations were also seen. There were reactive changes in the blood vessels, and the macrophage population was expanded and activated. Furthermore, apoptotic bodies were seen in the cytoplasm of the activated CD68+RFD-7+RFD-1+ macrophages pointing to the phagocytic capacity of these cells and their role in the clearance of the apoptotic cells from the tissues. These observations suggest that the persistance of CD8+ population in human immunodeficiency virus 1 infection is not a result of the presence of an abnormal CD8+ population but rather a result of an inappropriate over-stimulation of the CD8+ cells. PMID- 7778695 TI - Magnetic resonance imaging evaluation of the rotator cuff tendons in the asymptomatic shoulder. AB - Thirty shoulders in 20 volunteers (average age, 29 years; range, 17 to 49) with no shoulder symptoms or known abnormalities were scanned using magnetic resonance imaging. All scans were interpreted by one radiologist who was blinded to clinical data. Appearance of rotator cuff tendons on the images was graded. Grade 0 was normal, homogeneous low signal intensity structure. Grade 1 lesion was focal, linear, or diffuse intermediate signal through the tendon. Grade 2 lesion was high signal intensity within the tendon and less than full thickness. Grade 3 was high signal intensity through full thickness of the tendon. No supraspinatus or infraspinatus tendons were grade 0 (normal); all supraspinatus and infraspinatus tendons had grade 1 changes through the tendons; and 7 of 30 (23%) of the tendons had grade 2 changes. None of the 30 shoulders had grade 3 changes in the rotator cuff tendons. There is a wide array of abnormal magnetic resonance imaging signals in shoulders of young asymptomatic individuals, but they do not have full-thickness rotator cuff tears (grade 3 lesion). Nonenhanced magnetic resonance imaging may be of limited value in defining rotator cuff injury in a patient with shoulder pain unless a full-thickness rotator cuff tear is suspected clinically. PMID- 7778696 TI - Articular hypermobility and chondral injury in patients with acute patellar dislocation. AB - Thirty adolescents with acute, primary patellar dislocation were assessed for a relationship between articular hypermobility and chondral injury. The 15 patients without articular hypermobility had a 2.5 times increased frequency of articular lesions when compared with 15 patients with hypermobility. Assessment of articular hypermobility should be part of the examination in patients with patellar dislocation. PMID- 7778697 TI - A biomechanical comparison of lateral retinacular releases. AB - A lateral patellar retinacular release that transects the tendon of the vastus lateralis muscle may result in significant complications. To avoid such complications, the superior extent must be limited, and maximizing the inferior extent may be important in achieving an adequate release. The effective release of the patella from its lateral retinaculum was examined for 2 incision lengths using 10 fresh-frozen human cadaveric knees and comparing the medial displacement of the patella relative to the femur for 3 study groups (control, intact retinacula; Group A, retinacula cut from the inferior third of the vastus lateralis tendon down to the anterolateral arthroscopic portal; and Group B, retinacula cut from the inferior third of the vastus lateralis tendon down to the tibial tubercle) when a 22-N medially directed force was applied to the patella with the knee at 30 degrees and 60 degrees of flexion. The extended release (Group B) resulted in a significantly more effective release when compared with the standard release (Group A) or control group. This technique may allow an adequate release of the patella while preserving the function of the vastus lateralis muscle. PMID- 7778698 TI - "Aggressive" nontreatment of lateral meniscal tears seen during anterior cruciate ligament reconstruction. AB - Based on our experience, we hypothesized that certain lateral meniscal tears identified at the time of anterior cruciate ligament reconstruction can be left without removal or repair and that they will remain asymptomatic. We looked at 189 lateral meniscal tears that were left in situ at the time of anterior cruciate ligament reconstruction. At an average clinical followup of 2.6 years (range, 1 to 9 years) we found that 1) posterior horn avulsion tears, if left alone, do not cause clinical symptoms after anterior cruciate ligament reconstruction; 2) vertical tears totally posterior to the popliteus tendon are asymptomatic before and after reconstruction; and 3) other complete and incomplete lateral meniscal tears (vertical longitudinal, radial, or anterior vertical), if stable at the time of anterior cruciate ligament reconstruction, can be left in situ without becoming clinically symptomatic. All patients in the study population returned to their desired level of sporting activities by the time of follow-up evaluation. Our high clinical success rate in leaving selected lateral meniscal tears in situ is an "aggressive" attempt at meniscal salvage without increased morbidity from repair or resection. During the time we observed the patients (1 to 9 years), the lateral menisci remained asymptomatic. PMID- 7778699 TI - Nonoperative treatment of acute anterior cruciate ligament injuries in a selected group of patients. AB - Conservative treatment of acute anterior cruciate ligament injuries was recommended to selected patients, including those with sedentary occupations, low athletic demands, or ages greater than 30 years. Patients with generalized hyperligamentous laxity were excluded. Fifty-five of 61 patients were available at an average followup of 46 months from the time of initial injury. At followup, giving-way symptoms had not occurred in 23 patients (42%); in 22 (40%) giving way occurred occasionally. Of the 44 patients involved in high- or moderate-demand athletics, 33 (70%) were able to continue with moderate-demand sports. Presence of a medial collateral ligament sprain did not affect the longterm function. Forty-eight percent of the patients scored excellent or good (9 and 18 patients, respectively) on the Hospital for Special Surgery ligament scoring system; 8 (15%) later chose surgical reconstruction. The remaining 47 patients did not believe that their symptoms were severe enough to warrant any further intervention. In a group of individuals who are older and relatively inactive, nonoperative management of anterior cruciate ligament injuries can yield satisfactory results, provided the patients are willing to accept a modest amount of instability and a slight risk of meniscal injury. PMID- 7778700 TI - Correlation of joint line tenderness and meniscal lesions in patients with acute anterior cruciate ligament tears. AB - We sought to evaluate the accuracy with which joint line tenderness is associated with meniscal lesions in knees with acute anterior cruciate ligament tears. The physical assessment of joint line tenderness was performed at a mean of 8 days after the initial injury in 173 patients who subsequently underwent anterior cruciate ligament reconstruction. Identification of meniscal lesions was documented at the time of anterior cruciate ligament reconstruction. Eighty-nine patients (51%) had medial joint line tenderness; of this subgroup, 40 (45%) had a medial meniscal tear. Eighty-four patients (49%) had no medial joint line tenderness; of this subgroup, 29 (35%) had a medial meniscal tear. Fifty-nine patients (34%) had lateral joint line tenderness; of this subgroup, 34 (58%) had a lateral meniscal tear. One hundred fourteen patients (66%) had no lateral joint line tenderness; of this subgroup, 56 (49%) had a lateral meniscal tear. Medical joint line tenderness was 44.9% sensitive and 34.5% specific predicting medial meniscal injury. Lateral joint line tenderness was 57.6% sensitive and 49.1% specific in predicting lateral meniscal injuries. Therefore, we determined that the presence or absence of joint line tenderness in patients with an acute anterior cruciate ligament tear is not a reliable criterion to predict the likelihood of an associated meniscal tear. PMID- 7778701 TI - Meniscal injuries associated with acute anterior cruciate ligament tears in alpine skiers. AB - We reviewed the records of 315 patients receiving an arthroscopically assisted stabilizing procedure for an acute anterior cruciate ligament injury incurred while alpine skiing to evaluate associated meniscal injuries. Meniscal injuries were classified by type, location, and treatment of the tear. Of the 317 knees operated on, all demonstrated an anterior cruciate ligament tear at arthroscopy. Ninety-eight percent of the injuries (310) were diagnosed within 3 days of injury, and 97% (307) were reconstructed within 28 days of injury. All tears occurred in the intrasubstance of the ligament; 32% were isolated injuries and 68% were combined with other injuries. In 159 patients with 170 meniscal tears 141 of the tears (83%) were lateral and 29 (17%) were medial. The injury triad of anterior cruciate ligament-medial collateral ligament-lateral meniscus was seen nine times as often as the anterior cruciate ligament-medial collateral ligament medial mensicus combination. PMID- 7778702 TI - Allograft failure in cruciate ligament reconstruction. Follow-up evaluation of eighteen patients. AB - Previous authors have reported the efficacy of cruciate ligament allograft reconstruction of the knee suggesting that allograft strength is not significantly different than that of autografts. The purpose of this study was to elicit the cause of a higher-than-expected failure rate in cruciate ligament allograft reconstructions. After clinical diagnoses, 12 male and 6 female patients with cruciate ligament instability underwent intraarticular allograft reconstruction followed by an aggressive rehabilitation program. Deep-frozen, freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts were rehydrated, prestressed, and implanted by an open or arthroscopically assisted technique. Results revealed 6 of 18 failures. Knee instability, postoperative complications, and roentgenographic changes were evident. Evaluation of procurement technique showed that graft failure was significantly correlated with time to implantation. A significant difference in mean time from procurement and deep freezing to freeze-drying and sterilization between failed versus-successful grafts was 265.5 +/- 61.9 versus 66.8 +/- 43.8 days, respectively. Total mean time of failed grafts from procurement to implantation was significantly greater (528.3 +/- 75.1 versus 207.3 +/- 53.1 days) than for successful grafts. All graft failures came from the same batch number. These findings indicate that cruciate ligament allograft reconstruction can be successful; however, longer shelf life negatively affects graft integrity. PMID- 7778703 TI - Arthrometric results of arthroscopically assisted anterior cruciate ligament reconstruction using autograft patellar tendon substitution. AB - Sixty-two patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction with the middle-third patellar tendon autograft without extraarticular augmentation were retrospectively reviewed at a minimum 2-year (mean, 37-month) followup. A postoperative KT-1000 arthrometric evaluation revealed a mean maximum manual difference of 0.3 mm (range, -6 to +16). Ninety percent of the patients had a mean maximum difference of < or = 3 mm. Three patients had a > or = 5 mm mean maximum difference; positive pivot shifts were noted in two of these patients. Despite an early range of motion, early weightbearing protocol without an extraarticular backup, the pivot shift (92% negative) was reliably eliminated at postoperative followup. Arthrometric parameters were statistically reduced (P < 0.0001) from preoperative status and were consistent with the diagnostic criteria established for normal knees. There was no relationship established in the "tighter" knees (those with negative side to-side arthrometric differences) and the incidence of knee flexion contractures, patellar pain symptoms, Cybex extension deficit (> 20%), functional indices, or postoperative rating scales. PMID- 7778704 TI - Iliotibial band tenodesis: a new strategy for attachment. AB - We investigated the changes in distance between Gerdy's tubercle on the tibia and points on the posterior two thirds of the lateral surface of the lateral femoral condyle and adjacent lateral femoral shaft in 15 cadaveric knees. A three dimensional digitizer was used to quantify motion of the knee during flexion ranging from full extension to 120 degrees of flexion. Four load states were applied: internal, external, and neutral rotation, and quadriceps muscles loads based on one third of values in the literature for maximal isometric quadriceps muscles moments. The femoral location most isometric to Gerdy's tubercle was found to be strongly influenced by the load state. A 1.0 cm wide iliotibial band tenodesis was modelled by five straight lines arising from Gerdy's tubercle and attaching to a simulated washer at the junction of the lateral femoral condyle and shaft. Using this model and the motion data obtained from the cadavers, we investigated the effects of quadriceps muscles loading and external rotation of the knee on changes in the distances between these tibial and femoral attachments for each of the five lines. A 180 degrees twist modelled into the tenodesis significantly reduced the range of changes in distance (difference between the largest and smallest changes in distance among the lines for a given angle of flexion) for both of these load states. Therefore, a 180 degrees twist in the tenodesis can enhance isometry among the fibers of the tenodesis. This implies that a 180 degrees twist can enhance load sharing among the fibers of the tenodesis and, therefore, enhance the overall strength of the tenodesis. PMID- 7778705 TI - Collagen fibril organization in the patellar tendon autograft after posterior cruciate ligament reconstruction. A quantitative evaluation in a sheep model. AB - We replaced the posterior cruciate ligament in 30 skeletally mature sheep with a patellar tendon autograft using the central third of the ipsilateral patellar tendon. The healing autograft was compared with the contralateral posterior cruciate ligament and the patellar tendons and posterior cruciate ligaments of nonoperated animals. The collagen fibril diameters were analyzed using transmission electron photomicrographs of fibril cross sections taken at six periods during the 2 years after surgery. The patellar tendon and posterior cruciate ligament were characterized by a broad, nongaussian distribution of collagen fibril diameters. The autografts shifted to a unimodal distribution by an increase of small-diameter collagen fibrils. The frequency of small-diameter fibrils measuring up to 100 nm was 99% after 2 years. At that time, these small diameter fibrils represented 91.6% of the area covered by collagen fibrils. The mean diameter of the collagen fibrils in the autografts significantly decreased to 45% of the controls at Week 26 and remained at this level until the end of this study. The percentage of area covered by collagen fibrils per 1 micron 2 was 78% of the controls 2 years post-operatively. This study suggests that the patellar tendon autograft could not reproduce the collagen fibril organization of the posterior cruciate ligament. This may be a biologic factor responsible for inconsistent results in posterior cruciate ligament replacement. PMID- 7778706 TI - Collagen fibril populations in human anterior cruciate ligament allografts. Electron microscopic analysis. AB - We studied human anterior cruciate ligament allograft specimens by quantitative electron microscopy to analyze their collagen fibril populations. The specimens were procured at the time of second-look arthroscopy from the superficial region of the midzone of the anterior cruciate ligament grafts after synovial clearage. The grafts used for the anterior cruciate ligament reconstructions were from fresh-frozen allogenic Achilles, tibialis anterior or posterior, or peroneus longus or brevis tendons and had been implanted 3 to 96 months previously. By 12 months after surgery, the anterior cruciate ligament allografts consisted predominantly of small-diameter collagen fibrils (30 to 80 nm), which resulted in a unimodal pattern in the collagen fibril profile. The number of large-diameter fibrils (90 to 140 nm) within the allogenic tendon grafts had decreased. This predominance of small-diameter collagen fibrils persisted in almost all specimens older than 12 months. The anterior cruciate ligament allografts had collagen fibril profiles that did not resemble normal tendon grafts or normal anterior cruciate ligaments, even several years after surgery. PMID- 7778707 TI - Anatomic reconstruction of the lateral ankle ligaments using a split peroneus brevis tendon graft. AB - Fifteen patients with recurrent inversion ankle sprains and documented lateral ankle instability were treated with an anatomically oriented ligament reconstruction using a split peroneus brevis tendon graft. This reconstruction is designed to augment repair of the anterior talofibular and calcaneofibular ligaments without restricting subtalar motion. Of the 12 patients available for long-term followup, all were functionally improved, with no recurrences of instability. Stress radiographic examination at followup confirmed that mechanical stability had been restored in all ankles. Eversion strength and subtalar joint motion were maintained after surgery. We recommend this procedure in patients who require augmented reconstruction of the lateral ankle ligaments. PMID- 7778708 TI - Resection and repair for medial tennis elbow. A prospective analysis. AB - Fifty cases in 48 patients of intractable medial tennis elbow tendinosis (medial humeral epicondylitis) were treated surgically from 1985 to 1990 with identification and excision of the injured tendon, while retaining and closing the resection defect. All patients had symptoms that were aggravated by repetitive upper extremity activities and had failed to improve with nonoperative therapy. At surgery, the flexor carpi radialis-pronator teres interval was involved in 28 cases. Histologic examination revealed angiofibroblastic tendinosis and fibrillary degeneration of collagen. Postoperative followup averaged 37 months. An analog scale was used to analyze pain intensity, and pain occurrence was evaluated by a pain phase scale. All patients reported partial or complete pain relief postoperatively (improvement in their pain phase and pain intensity scales). Preoperatively, 14 patients had pain at rest; all 14 had relief of this pain postoperatively. Ten patients did not return to their sporting or occupational activities. Objective dynamometer strength testing revealed a significant improvement postoperatively in all patients; no major complications were seen in this series. A large percentage of patients who fail conservative treatment for medial humeral epicondylitis (tendinosis) can obtain pain relief and return to activities with the described operative technique. PMID- 7778709 TI - Acute gamekeeper's thumb. Quantitative outcome of surgical repair. AB - Ten consecutive patients with 11 complete ulnar collateral ligament tears who had early surgical repair were evaluated at an average of 42 months' followup. The mean arc of motion at the metacarpophalangeal joint at 50.9 degrees was less than the 73.7 degrees seen in the uninjured thumbs. At the interphalangeal joint, the mean arc of motion in the injured thumb was 101.6 degrees compared with 112.6 degrees on the uninjured side. Ulnar laxity was decreased slightly compared with the contralateral thumb (14.0 degrees versus 15.3 degrees) and radial laxity was 10.3 degrees on both sides. The mean grip strength and key pinch were similar between the injured and uninjured sides: grip strength was 32.3 kg in the injured thumbs and 34.0 kg in the uninjured; key pinch was 8.1 kg in the injured thumbs and 8.8 kg in the uninjured. Good stability with slight decrease in motion was obtained in our patients. PMID- 7778710 TI - The effects of anabolic steroids on rat tendon. An ultrastructural, biomechanical, and biochemical analysis. AB - Forty-eight male rats were randomly separated into four groups: a control group, a group treated with anabolic steroids, a group treated with daily exercise, and a group treated with both steroids and exercise. At 6 weeks, biomechanical, ultrastructural, and biochemical testing was performed on the Achilles tendons of half of the rats in each group. The remaining rats continued in the experimental protocol, but steroid administration was discontinued. Similar testing was then performed on the remaining rats at 12 weeks. Testing showed anabolic steroids produced a stiffer tendon that absorbs less energy and fails with less elongation; tendon strength was unaffected. Effects were entirely reversible on discontinuation of the steroids. Light microscopic analysis revealed no changes in the appearance of the fibrils. No change in fibril diameter or shape was noted on electron microscopic analysis. Biochemical testing revealed no change in qualitative immunofluorescence staining with Type III collagen or fibronectin. Abuse of anabolic steroids is a widespread problem among competitive athletes; consequently, complications after their use are seen with increasing frequency. Knowledge of the effects of these drugs on tendon and the musculotendinous unit may prove helpful in counseling athletes who use anabolic steroids. PMID- 7778711 TI - Kinetics of baseball pitching with implications about injury mechanisms. AB - Elbow and shoulder kinetics for 26 highly skilled, healthy adult pitchers were calculated using high-speed motion analysis. Two critical instants were 1) shortly before the arm reached maximum external rotation, when 67 N-m of shoulder internal rotation torque and 64 N-m of elbow varus torque were generated, and 2) shortly after ball release, when 1090 N of shoulder compressive force was produced. Inability to generate sufficient elbow varus torque may result in medial tension, lateral compression, or posteromedial impingement injury. At the glenohumeral joint, compressive force, joint laxity, and 380 N of anterior force during arm cocking can lead to anterior glenoid labral tear. Rapid internal rotation in combination with these forces can produce a grinding injury factor on the labrum. After ball release, 400 N of posterior force, 1090 N of compressive force, and 97 N-m of horizontal abduction torque are generated at the shoulder; contribution of rotator cuff muscles in generating these loads may result in cuff tensile failure. Horizontal adduction, internal rotation, and superior translation of the abducted humerus may cause subacromial impingement. Tension in the biceps tendon, due to muscle contraction for both elbow flexion torque and shoulder compressive force, may tear the anterosuperior labrum. PMID- 7778713 TI - Functional anatomy of the flexor pronator muscle group in relation to the medial collateral ligament of the elbow. AB - To describe the relationship of the pronator teres, flexor carpi radialis, flexor digitorum superficialis, and flexor carpi ulnaris muscles to the medial collateral ligament at 30 degrees, 90 degrees, and 120 degrees of elbow flexion, we dissected 11 cadaveric specimens. The flexor carpi ulnaris muscle is the predominant musculotendinous unit overlying the medial collateral ligament in the majority of cases and is the only one at 120 degrees of elbow flexion. The flexor digitorum superficialis muscle is the only other significant contributor. The medial collateral ligament is the primary stabilizer of the medial elbow with elbow flexion greater than 30 degrees, as in throwing. The flexor carpi ulnaris muscle, because of its position directly over the medial collateral ligament, and the flexor digitorum superficialis muscle, with its near proximity and relatively large bulk, are the specific muscles best suited to provide medial elbow support. This is especially relevant to overhand throwing athletes who encounter extreme valgus force across the elbow during the cocking and acceleration phases of the throwing motion. Exercise and conditioning of the medial elbow musculature, specifically the flexor digitorum superficialis muscle and the flexor carpi ulnaris muscle, may prevent injury or assist in rehabilitation of medial elbow instability, especially in overhand throwing athletes. PMID- 7778712 TI - Osteoarthritis after arthroscopic partial meniscectomy. AB - The purpose of this study was radiologic assessment of osteoarthritis after arthroscopic partial meniscectomy. At an average followup of 53.5 months, 284 consecutive patients were retrospectively evaluated clinically and radiologically. Two hundred forty-seven patients had been treated for medial (Group I) and 37 for lateral meniscal tears (Group II). Preoperative radiographs were compared with those at followup and were classified. The results were analyzed statistically. Osteoarthritic changes were classified as being worse in 38% of the patients after medial and in 24% of the patients after lateral arthroscopic partial meniscectomy. Further subclassification and comparison of patients with or without already existing articular surface damage at the time of arthroscopy were not found to have significant impact on the prevention of osteoarthritic changes. Patients who were older than 40 years of age and who had undergone arthroscopic partial medial meniscectomy were radiologically classified with a significantly higher rate of osteoarthritis than patients who were younger than 40 years. Partial medial or lateral meniscectomy leads to a significant increase of osteoarthritic changes, even when this intervention is performed arthroscopically. PMID- 7778715 TI - [Morphological and morphometric study of the tympanic and mastoid portions of the fallopian aqueduct]. AB - In surgery of the temporal bone the best way to avoid injuries to the facial nerve is to be acquainted with its location in all the surgical steps of the procedure scheduled. That is to say: an exact knowledge of its normal intratemporal run, having always in mind some characteristic landmarks, is absolutely essential. This work has been done through drilling 92 human temporal bones, measuring the length of both the tympanic and mastoidal segments and also considering the bending of the 2nd knee of the nerve. In the issue the mastoidal portion resulted the most straight (by half of the cases) whereas the tympanic one was slightly sloping downwards between the lateral semicircular canal upwards and the oval window below. Topographically has not been possible to establish neither a strict correlation between the location of the pyramide and the 2nd knee nor this knee was found by uns (in contrast to other AA's findings) at higher angle than 90 degrees in our specimen. PMID- 7778714 TI - The effect of elastic bandages on human knee proprioception in the uninjured population. AB - Elastic bandages are often used to treat musculoskeletal disorders, even though there is little scientific evidence currently to support this generalized practice. We tested the hypothesis that elastic bandages improve proprioception of the bandaged joint during their use, and that this benefit was more than temporary. The uninjured human knee was used as a model. Fifty-four volunteers (54 knees), aged 22 to 40 years, were asked to identify a prior set joint angle as their knee was passively extended. Each knee was tested without the elastic bandage, immediately after bandage application, after 1 hour of bandage wear, and finally after removal of the bandage. Results showed that elastic bandages significantly improved knee joint proprioception in the uninjured knee during the entire interval of their use (mean decrease in inaccuracy of 1.0 degree, equivalent to 25% improvement, P < 0.05), and that this benefit was lost when the bandage was removed. The magnitude of the improvement, or the potential beneficial effect of the bandage, was inversely related to the participant's inherent knee proprioceptive ability, which was demonstrated in the test group before the initial application of the bandage. PMID- 7778716 TI - [Descriptive analysis of evoked laryngeal potentials of the brainstem in rabbits]. AB - The present study evaluated comparatively the laryngeal brainstem responses (LBR) evoked, through electrical stimulation of the superior laryngeal nerve, in 2 groups of mature rabbits, using a far field technique. Each group is formed according to the shifting of the stimulation parameters followed for the research, namely: intensity (from 0.5 to 3 mA), stimulus frequency (from 2 stimuli/second to 5 stimuli/second) and total stimulation time (between 200 microseconds to 500 microseconds). Afterwards the values attained are compared with those supplied for the control-group (having 2 mA intensity, 4 stimuli per second and 100 microseconds as time). We got significative statistical differences regarding the stimulus intensity and the outcome is a shortening in latency wawe of LBR when using 3 mA. PMID- 7778717 TI - [Leishmaniasis and ENT]. AB - Three cases of the infrequent mucocutaneous Leishmaniasis, with nasal involvement in two of them and affection of the hypophrarynx and larynx in the other one are presented. We remark, in the case with laryngeal disease, that it was the onset of an AIDS in a patient unknown to be HIV+. Leishmaniasis of the larynx has not been described before as the onset of an AIDS. Symptomatology, evolution and treatment of this disease are revised, pointing out the increasing association, in our country, between leishmaniasis and AIDS, and considering the possibility of including the leishmania infection as an AIDS criteria in HIV+ patients, and to rule out an IVH infection in a patient with an atypical leishmaniasis either for the site involved or the evolutive course of the disease. PMID- 7778718 TI - [Approach to the laryngeal reflex through the study of laryngeal evoked potentials from the brainstem in rabbits]. AB - The present study evaluated the laryngeal brainstem response evoked by electrical stimulation of the superior laryngeal nerve in rabbits, using a far-field technique with an intensity of 2 mA, 100 microseconds duration and frequency of 4/second. Five reproducible positive and four negative waves, both reproducible, were obtained and they may represent the laryngeal brainstem activity. PMID- 7778719 TI - [Pilomatrixoma of the auricle. Differential diagnosis with carcinoma pilomatrixoma]. AB - A 34 year-old man, with a two centimeter diameter quickly growing nodule on the auricular pavillion is presented. After mass excision the histologic diagnosis of pilomatrixoma was made. Pilomatrixoma is a rare benign tumor arising on the hair matrix. The differential diagnosis include pilomatrix carcinoma, a locally and recurrent aggressive tumor capable to make pulmonary metastasis. A review of the literature is included, with emphasis on the clinical and histopathological aspects and the therapeutic attitude. PMID- 7778720 TI - [Adjuvant chemotherapy in the treatment of pharyngolaryngeal cancers in advanced stages]. AB - Since 1980 we use adjuvant chemotherapy in advanced laryngopharyngeal carcinomas. These cases were resectable and unresectable lesions with tumoral extent to the pharynx as a common characteristic. We analyze the survival of the first 50 cases treated with chemotherapy followed by: A) surgery and radiotherapy (36 cases) and B) radiotherapy alone (14 cases). Results of this not randomized study are compared with a historic group of advanced laryngopharyngeal carcinomas (T4/N+) treated with conventional therapy (surgery +/- radiotherapy). Response to chemotherapy was complete or partial (> 50% reduction) in 56 percent of the patients. There was improvement in overall survival and five-years disease-free survival in the latter group compared with those who did show any response (p < 0.01). We would point out that disease-free survival of the group A was better than historic group (60% vs 36%, p < 0.05), although these result should be carefully interpreted. Laryngeal preservation was achieved in 47 percent in the group A by modification of the initially scheduled radical surgery, in selected cases. PMID- 7778721 TI - [Oncogenic activity of head and neck tumors]. AB - Some types of malignant neoplasms are consequence of genetic changes. The starting of oncogenesis begins when some genetic alterations arises, or the genome acquires some peculiar and pathological traits owing to the action of physical, chemical or viral agents. These alterations set in motion an activatory phenomenon upon the proto-oncogene which is turned into an oncogene. The oncogene is responsible for fixed alterations of the genome inducing to an anomalous cellular growth. In squamous carcinomata of the head and neck has been observed mutations of the p-53 tumour-suppressor gene, alike amplifications of the ras gene, of the C-myc proto-oncogene and also of the epidermal growth factor gene (EGFG). The viruses induce mutations on the genome. That would be the explanatory reason for the association carcinoma of the rhinopharynx-Epstein-Barr virus. PMID- 7778722 TI - Australia and New Zealand Intensive Care Society Statement and Guidelines on Brain Death and Model Policy on Organ Donation. PMID- 7778723 TI - Successful anaesthetic management of a patient with thyrotoxic hypokalaemic periodic paralysis for coincidental appendicitis. PMID- 7778725 TI - Brain death and organ donation. PMID- 7778724 TI - Brain death and organ donation. PMID- 7778726 TI - Spinal subdural haematoma following combined spinal-epidural anaesthesia. PMID- 7778727 TI - Anaesthesia and undiagnosed myasthenia gravis. PMID- 7778728 TI - Difficult intubation following bilateral subtemporal decompression. PMID- 7778729 TI - Respiratory arrest with patient-controlled analgesia. PMID- 7778730 TI - Preventing epidural overdose. PMID- 7778731 TI - Intramuscular ketorolac for analgesia after laparoscopic sterilization. PMID- 7778732 TI - Ondansetron for the prevention of nausea and vomiting. PMID- 7778733 TI - Foley catheter and post-nasal bleeding. PMID- 7778735 TI - Topical anaesthesia for cataract surgery. PMID- 7778734 TI - Dilating veins, a simple approach. PMID- 7778736 TI - Circle absorption system hazard. PMID- 7778737 TI - HME plus heated humidifier danger. PMID- 7778738 TI - Predicting outcome in anaesthesia. PMID- 7778739 TI - Chlorhexidine catheter lubricant anaphylaxis. PMID- 7778740 TI - A personal comment: whole brain death versus cortical death. PMID- 7778741 TI - Brain death and organ donation--a point of view. PMID- 7778742 TI - Further thoughts on brainstem death. PMID- 7778743 TI - Brain death: an update on the North American viewpoint. PMID- 7778744 TI - The physiological changes associated with brain death--current concepts and implications for treatment of the brain dead organ donor. AB - The profound physiological disturbances associated with severe intracerebral pathology have long been recognized. These changes have also been described in the brain dead potential organ donor but have only been studied since the early 1980s. Physiological disturbances in the brain dead organ donor result in a diffuse vascular regulatory injury and a diffuse metabolic cellular injury. The net result of these changes is an inexorable deterioration of all organs and eventual "cardiovascular death" of the patient. This paper reviews these physiological changes and the effect they may have on solid transplantable tissues, and discusses the management of brain dead organ donor with regard to these changes. Current concepts of brain death and how they may affect the interpretation of the observed physiological changes are also reviewed. PMID- 7778745 TI - Skinner's chloroform mask. PMID- 7778746 TI - Clinical confirmation of brain death. PMID- 7778747 TI - The imaging of brain death. PMID- 7778748 TI - Medical management of the (potential) organ donor. PMID- 7778749 TI - An overview of transplantation in Australia. AB - Organ donation in Australia has permitted transplantation of the kidneys, heart, lung, pancreas, liver and cornea. Each of these programs has successfully provided life and rehabilitation to Australians with end-stage failure of one or more organs. The programs are supported by an infrastructure of donor coordinators, matching and allocation procedures and national co-operative registries, which record and publish the outcome of each form of transplant. Four national organizations work to promote transplantation: the Transplantation Society of Australia and New Zealand; the Australasian Transplant Coordinators' Association; the Australian Kidney Foundation; and the Australian Co-ordinating Committee for Organ Registries and Donation. Australian donation rates are lower than in many, but not all, comparable developed democracies, however utilization of those donor offers is high, leading to 698 organ transplants being performed in 1993. PMID- 7778750 TI - Organ donation in Australia: an historical overview, current directions and future principles. PMID- 7778751 TI - A survey of personal and professional attitudes of intensivists to organ donation and transplantation. AB - A questionnaire survey was carried out to examine the attitudes and practices of Australian and New Zealand intensivists with regard to brain death and organ donation. A return rate of 82.5% was achieved. Fifty-eight per cent had written evidence of their own wishes to donate organs and 94% would agree to donation from a dependent. At least one intensivist is involved in certifying brain death on 95% of occasions. Intensivists are involved in the request for organ donation over 90% of the time although one-third do not believe that it is their role to request organ donation. Although two-thirds believe that the family should always be approached for organ donation, another 52 out of 254 indicated that it was their (the intensivist's) role to decide if families should be asked for organ donation. Possible reasons for not requesting are language or other communication problems, perceptions of cultural differences and degrees of family distress. Twenty per cent of respondents do not provide haemodynamic support before brain death confirmation. Australian and New Zealand intensivists overwhelmingly support the concept of brain death, current methods of confirmation of brain death, organ donation and transplantation. Possible reasons behind loss of potential donors include decisions not to resuscitate both before and after brain death is confirmed. Perceptions of family grief and cultural differences clearly inhibit requests for organ donation. A very few units have an effective policy on approaching families about organ donation. Intensivists have almost exclusive control over requests for organ donation and thus bear a full professional responsibility for this element of hospital practice. PMID- 7778752 TI - The identification of potential cadaveric organ donors. AB - Most Australian transplantation programs are severely restricted in their activities by a limited availability of cadaveric donor organs. To investigate possible reasons for this problem, an audit was undertaken over three 12-month periods of all deaths in 13 hospitals in New South Wales and the Australian Capital Territory. From 7406 deaths, 271 patients were classified as having been realistic, medically suitable potential donors. Of these, only 60 (22%) became actual donors. In the other 211 patients, donation did not occur because of unsuccessful resuscitation (30%), permission refusal by relatives (34%), and failure to identify or support the potential donors (36%). If the impediments to organ donation which were identified in this study could be overcome, allowing a greater number of potential donors to become actual donors, the chronic shortage of cadaveric donor organs for transplantation could be at least partly relieved. PMID- 7778753 TI - Obtaining consent for organ donation in nine NSW metropolitan hospitals. AB - Organ donation rates vary markedly around the world. In an attempt to analyse why some patients' families are not asked about organ donation, the case notes of 6080 patients who died over a twelve-month period from April 1991 to March 1992 in nine hospitals in Sydney, NSW, were studied. Irreversible coma occurred in 515 patients. Of these, 177 were considered to be potentially brain dead donors, 126 of whom had a formal diagnosis of brain death. The clinicians caring for the patients at the time of death were asked at follow-up about the reasons for not considering donation, or the reasons for family refusal. Consent to proceed to organ donation was requested in 112 cases (49 donated and 63 refused) and not requested in 65. Analysis of the proportions asked and consenting in each hospital revealed no correlation. Half of the families refusing gave no reason (24/50) while eleven gave religious or cultural reasons, and six expressed a desire to prevent mutilation of the body as their primary reason for not consenting. There was universal failure to gain consent from families when the patient was not in an Intensive Care Unit. Analysis of those patients of whom consent was not sought showed that they died more quickly after admission, were older and died from causes other than trauma or intracranial haemorrhage. The odds of the family being asked dropped by about half as the age increased from one group to the next.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778755 TI - Donor families' experience of organ donation. AB - This retrospective study surveyed families who consented to organ donation in the State of Queensland, Australia, from January 1991 to December 1992 inclusive, and evaluated their experience of the organ donation process. The survey questioned families in relation to the preparation they received, their understanding of brain death, the request process, influencing factors, and post donation follow up. One hundred and eight families consented to organ donation over this 24-month period. Twelve families of paediatric donors under the age of twelve years were excluded, and twelve families were not able to be contacted. Of the remaining 84 families, 42 participated in this study. Overall the study results indicated a positive attitude towards the organ donation process. The majority of families did not find the process stressful and indicated that they were provided with sufficient information and preparation, and that the request was made in a sensitive manner. A few important issues and areas for improvement were highlighted: in particular, the need for families to have an opportunity to view the body after procurement, and the importance of counselling throughout and after the donation process. PMID- 7778754 TI - A survey of families of brain dead patients: their experiences, attitudes to organ donation and transplantation. AB - A questionnaire survey of 69 families of brain dead patients is reported. The study population included those who had been asked about organ donation as well as those who had not, those who had agreed to organ donation and those who had declined. Their experiences and their perceptions of treatment and explanations of underlying disease, brain death and organ donation were examined. Their own knowledge of and attitudes towards organ donation as well as the prior knowledge and wishes of their deceased relative were also explored. Statistical analysis did not show any differences between the three groups of families with regard to their experiences, their perceptions of the treatment they received, or in the resolution of their grief. Family members who had agreed to organ donation were significantly more likely to donate their own organs and to be more resolved in their grief. There was a strong correspondence between the attitudes of respondents and their agreement or otherwise to donate their relatives' organs. One quarter, however, made the opposite choice for their relative, where their relative's wishes were known. There was a highly significant relationship between those who had previously discussed organ donation to have expected to be asked or to raise the subject themselves. Hospital treatment in general did not appear to have any effect on the decision to donate. Involvement in organ donation was felt by most of the donor families to have been helpful to the grieving process. PMID- 7778756 TI - Can cadaveric organ donation rates be improved? AB - There are many reasons why potential cadaveric organ donors may fail to become actual donors. These include permission refusal by the next of kin, incorrect assumptions about medical suitability and, occasionally, an excessive workload in the intensive care unit. Some potential donors currently regarded in Australia as "unrealistic" might become actual donors if attitudes were to change towards ventilation of patients with a clearly hopeless prognosis who have expressed a wish to be organ donors. "Required request" legislation ignores the wishes of the potential donor and "presumed consent" laws also present some ethical difficulties, but a suggested "required response" process could ensure that an individual's wishes concerning organ donation would be known and able to be carried out after death. For the present, however, it is clear that operating within existing Australian legislation and abiding by currently accepted codes of practice, we can still find considerable scope for improving cadaveric organ donation rates. PMID- 7778757 TI - Quantitation of red blood cell folates by stable isotope dilution gas chromatography-mass spectrometry utilizing a folate internal standard. AB - We report a new gas chromatography-mass spectrometry (GC-MS) method of measurement of red blood cell folates utilizing a stable isotope-labeled bacterial synthesized folate internal standard. The GC-MS method exploits the fact that the common feature of all folate molecules is a p-aminobenzoic acid moiety sandwiched between a pteridine ring and a polyglutamate chain of varying length. In this method, red blood cell folates together with a folate internal standard are specifically purified using bovine folate binding protein and the folates are subsequently chemically cleaved to p-aminobenzoic acid, pteridines, and glutamic acids. Since all six carbon atoms of the benzene ring in the p aminobenzoic acid moiety of the folate internal standard are labeled with [13C], it is possible to use selected ion monitoring and stable isotope dilution GC-MS to quantitate folates. The method appears to be sensitive, specific, and accurate. The method has been applied to generate a reference range of red blood cell folates based on assay of 25 normal individuals. PMID- 7778758 TI - A novel and simple method to assay the activity of individual protein kinases in a crude tissue extract. AB - Protein kinases and phosphatases play an important role in a variety of cellular functions. Thus, it is of interest to develop an assay system that can be used to quantify the activity of individual enzymes specifically in a crude cellular extract, is simple to perform, and is amenable to automation. Here we report on the development of a protein kinase assay that addresses these points and circumvents the pitfalls of existing methodologies. The assay is based on the high affinity and strong binding of streptavidin toward biotin-linked peptide substrates. The biotinylated peptide substrate is phosphorylated by the cognate protein kinase using [gamma-32P]ATP under optimal enzyme condition, and the phosphorylated peptide product is then captured by a streptavidin-linked disk. After removal of free [gamma-32P]ATP, the 32P incorporated into the peptide substrate can be used as an expression of enzyme activity. In contrast to the commonly used phosphocellulose method, only the phospho-, biotinylated peptide (and not other phosphorylated proteins present in the extract) will bind to the disks, thus giving a true estimate of enzymatic activity. In addition to specificity, this assay does not require the peptide substrate to contain basic amino acids or to be modified by the addition of basic amino acid residues as required for the phosphocellulose method which may result in altered specificity of the substrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778759 TI - Isotope dilution gas chromatographic-mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces, with preliminary results in omnivorous and vegetarian women. AB - We describe an isotope dilution gas chromatographic-mass spectrometric (GC/MS) method for the identification and quantitative determination of the lignans enterolactone, enterodiol, and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin, and genistein in feces. Following the addition of deuterated internal standards for all compounds, the feces samples are extracted and purified in several ion exchange chromatographic steps. Following formation of trimethylsilyl ethers, the samples are analyzed by combined capillary column GC/MS in the selective ion monitoring mode and corrected for all losses during the procedure using the deuterated internal standards. Results on the reliability of the method and values for nine Finnish omnivorous and nine vegetarian women are presented. PMID- 7778760 TI - A fluorometric assay for pyridoxal kinase applicable to crude cell extracts. AB - We have developed an assay for pyridoxal kinase which takes advantage of the intense fluorescence yield of the oxime of pyridoxal or pyridoxal-5'-phosphate and the substantial difference in the rates of formation of these two oximes. Evidence is presented which demonstrates that the assay is linear with respect to time and amount of protein and is applicable to the activity in crude cell extracts as well as purified enzyme. PMID- 7778761 TI - A novel method for analysis of viral proteinase activity encoded by hepatitis C virus in cultured cells. AB - We developed a novel method for analysis of hepatitis C viral proteinase activity in cultured cells, in which the proteinase activity was measured as the enhancement of reporter gene expression. In this system, plasmids encoding a reporter gene, the enzyme gene, and the substrate gene were simultaneously transfected into COS-1 cells. The reporter plasmid contains chloramphenicol acetyltransferase (CAT) gene downstream of an enhancer/promoter sequence derived from the human T-cell leukemia virus type-1 (HTLV-I) long-terminal repeat (LTR). The substrate expression plasmid was a triple chimera; HCV nonstructural protein 2 (NS2) and the Tax1 protein of HTLV-I sandwiched the substrate polypeptide, which was inserted upstream of Tax1. This method assumes that since the HCV NS2 appears to be located in the lipid bilayer of endoplasmic reticulum (ER) membranes, the Tax1 of the chimeric substrate was trapped on the surface of the ER in the absence of HCV proteinase activity. After release from the chimera by HCV proteinase-dependent cleavage, Tax1 could transactivate the expression of the CAT gene through the enhancer sequence of HTLV-I LTR. This system should enable us to simply and safely screen the potential antiviral activity of proteinase inhibitors in vivo, although this system may be limited to proteinase inhibitors that are permeable to the plasma membrane. PMID- 7778762 TI - A capillary zone electrophoresis assay for the nucleoside transfer enzyme adenosine diphosphate-glucose pyrophosphorylase. AB - Conditions are described for a capillary zone electrophoresis-based assay of ADP glucose pyrophosphorylase, the first enzyme in the de novo synthesis for alpha glucan synthesis in plants and bacteria. ATP, ADP-glucose, and other adenine derivatives are effectively resolved and quantified in 12 min of electrophoresis. The method requires minimal sample manipulations and no postincubation hydrolyses, is effective over a wide range of enzyme and substrate concentrations, has a sensitivity comparable to radioisotope assays, and yields reproducible results in either the forward and reverse directions. Moreover, the assay is applicable to other enzymes that utilize nucleosides or their bases as substrates or products. PMID- 7778764 TI - Characterization of glycopeptides from recombinant coagulation factor VIIa by high-performance liquid chromatography and capillary zone electrophoresis using ultraviolet and pulsed electrochemical detection. AB - Four glycopeptide (GP) fractions containing glycosylated Asn 322 were isolated from a tryptic digest of recombinant coagulation factor VII by reversed-phase HPLC (RP-HPLC). Characterization of the GPs by enzymatic desialylation and RP HPLC as well as by enzymatic deglycosylation, RP-HPLC, and high-pH anion-exchange chromatography indicated that the four GPs consisted of the same decapeptide but with 0, 1, 2, or 4 residues of sialic acid. In comparison to HPLC, capillary zone electrophoresis (CZE) using uv and pulsed electrochemical detection (PED) afforded improved separation of GPs from each other and from contaminants. CZE-uv and CZE-PED of the desialylated GPs and deglycosylated GPs corroborated the results obtained with the chromatographic methods. PMID- 7778763 TI - A homogeneous immunofluorescence assay based on dye-sensitized photobleaching. AB - A novel homogeneous immunoassay requiring only one incubation step, and applicable in principle to the determination of low- as well as high-molecular weight substances, has been developed. The method is based on (a) photooxidation by singlet oxygen (1O2) of a fluorescent substrate (1,3-diphenylisobenzofuran, DPBF) embedded in unilamellar vesicles on the surface of which antibody to the analyte antigen is covalently attached (DPBF-immunoliposomes); (b) generation of singlet oxygen, upon illumination, by a chromophore (erythrosine) covalently attached to an antibody (Ab*) or antigen (Ag*); (c) formation of a "sandwich"- or "competition"-type complex whereupon the singlet oxygen-generating chromophore conjugate (Ab* or Ag*) and immunoliposome-embedded DPBF are brought into close proximity. Competition- and sandwich-type model assay systems for the detection of protein antigens and viruses were investigated. The detection range with protein antigens in competition- and sandwich-type assays was three (10(-10) - 10(-7) M) and two (10(-10) - 10(-8) M) orders of magnitude, respectively. With poliovirus using a sandwich-type assay, the detection range was 10(2) - 10(6) plaque-forming units per milliliter (pfu/ml). PMID- 7778765 TI - Electrochemical determination for enzymic production of ultimate carcinogen from tryptophan pyrolysate by rat hepatic microsomes. AB - This study established a rapid and sensitive method of determining the level of the ultimate carcinogen from 3-amino-1-methyl-5H-prido[4,3-b]indole (Trp-P-2) produced by rat hepatic microsomes. An electrochemical detector (ECD) used with high-performance liquid chromatography (HPLC) gave a linear calibration curve for synthetic N-hydroxy-Trp-P-2 (the ultimate carcinogenic form) at concentrations ranging between 0.3 and 340 pmol. The enzymic production of N-hydroxy-Trp-P-2 from Trp-P-2 was also determined by the ECD with HPLC. Hepatic microsomes (0.2 mg as protein) from rats treated with methylcholanthrene (MC) and phenobarbital (PB) were incubated with Trp-P-2 for 5 min. The mixture was centrifuged with acetonitrile and the supernatant was then analyzed using HPLC. The ECD determined the level of N-hydroxy-Trp-P-2 to levels nearing 1 pmol, and the preparation before submission to the HPLC took such a short time (5 min) that N-hydroxy-Tr-P 2 did not have sufficient time to decompose. Then, the microsomal N-hydroxylation activity on Trp-P-2 was compared with five different sources of microsomes. The microsomes from rats treated with MC plus PB, MC, PB, or polychlorinated biphenyl showed an activity level (mol/min/mol P450 enzymes) of 2.41 +/- 0.19, 1.92 +/- 0.21, 0.048 +/- 0.017, and 1.79 +/- 0.15, respectively, and those from untreated rats showed no activity. This method was useful for evaluating the N hydroxylation activity of P450 enzymes. PMID- 7778766 TI - Two-color double in situ hybridization using enzymatically hydrolyzed nonradioactive riboprobes. PMID- 7778767 TI - Amplification of the entire mitochondrial DNA by polymerase chain reaction in two large overlapping segments. PMID- 7778768 TI - Quick preparation of mitochondrial DNA fractions free from nuclear DNA for polymerase chain reaction amplification. PMID- 7778770 TI - Separation of two proline-containing peptides by capillary electrophoresis. PMID- 7778769 TI - A spectrophotometric method for quantitative determination of allicin and total garlic thiosulfinates. PMID- 7778771 TI - Extraction and determination of ascorbate and dehydroascorbate from plant tissue. PMID- 7778772 TI - Determination of S-adenosyl-L-methionine: L-methionine S-methyltransferase activity by selective adsorption of [methyl-3H]S-adenosylmethionine onto activated charcoal. PMID- 7778774 TI - Transformation of Escherichia coli increases 260-fold upon inactivation of T4 DNA ligase. AB - It was possible to obtain high-efficiency transformation of E. coli MC1061 by the following modifications of the standard procedure: cells were harvested at A600 of 550-650, washed with 1, 1/2, and 1/40, and were resuspended in 1/500 culture vol of 1 mM Hepes, pH 7.0, to a cell concentration of 6 x 10(10)-6 x 10(11) cells/ml. Electrocompetent cells were used immediately for electroporation to yield 1.3 +/- 0.5 x 10(9) (mean +/- SD) transformants micrograms of plasmid DNA, which is comparable to the efficiency of bacteriophage lambda infection. Alternatively, cells can be stored frozen in 10% glycerol, although glycerol reduced transformation efficiency to approximately 30% (data not shown). Freezing and thawing of glycerol-treated cells did not result in any further loss of transformation efficiency (data not shown). This study showed that it is crucial to inactivate the T4 DNA ligase prior to electrotransformation of ligated DNA, which can be ensured by the introduction of a simple heat inactivation step, increasing the number of transformants by 260-fold. Although this paper focuses on the use of E. coli MC1061/p3, the experiments were repeated with a different plasmid in the parental strain E. coli MC1061 and showed the same result (data not shown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778773 TI - Overcoming polymerase chain reaction inhibition in old animal tissue samples using ethidium bromide. PMID- 7778775 TI - Dibromobimane as a fluorescent crosslinking reagent. PMID- 7778776 TI - Fluorometric assay of GTPase activity: application to the couple elongation factor eEF-2-ribosome. PMID- 7778777 TI - Enzymatic synthesis of guanine nucleotides labeled with 15N at the 2-amino group of the purine ring. AB - GMP and dGMP labeled with 15N at the 2-amino group of the purine ring was obtained enzymatically from NH4Cl (> 99 at.% 15N) and from IMP or dIMP, respectively, by several reactions involving IMP-dehydrogenase, GMP-synthetase, adenylate kinase, and creatine kinase. The first three enzymes were obtained by overexpression in Escherichia coli of the corresponding genes. The isotope content of the primary amino group of guanine determined by mass spectrometry after acid hydrolysis of nucleotides was found higher than 98 at.% 15N. The proton NMR spectrum of [15N]GMP in solution in the absence of nitrogen decoupling showed a doublet with a coupling constant of 92 Hz. When nitrogen decoupling was used during the acquisition time, the doublet was replaced by a single peak at 6.47 ppm, indicating that the corresponding proton is bound to 15N. PMID- 7778778 TI - Inhibition of human spleen protein tyrosine kinases by phenolic compounds. PMID- 7778779 TI - Desalting inositolpolyphosphates by dialysis. PMID- 7778781 TI - A procedure for the rapid preparation of guanosine tetraphosphate (ppGpp) from Escherichia coli ribosomes. PMID- 7778782 TI - A nonradioactive method to determine levels of in vitro transcription in nuclear extracts. PMID- 7778780 TI - A low-pH reverse-phase high-performance liquid chromatography system for analysis of the phenylthiohydantoins of S-carboxymethylcysteine and S carboxyamidomethylcysteine. PMID- 7778783 TI - Direct mass spectrometric analysis of glycosphingolipid transferred to a polyvinylidene difluoride membrane by thin-layer chromatography blotting. AB - A simple, rapid method for the analysis of glycosphingolipid that combines "thin layer chromatography (TLC) blotting" and mass spectrometry is reported. Glycosphingolipids developed by TLC were transferred to a polyvinylidene difluoride membrane by TLC blotting, after which the glycosphingolipid band on the membrane was excised and placed on a mass spectrometer probe tip, and a few microliters of triethanolamine was added as the matrix. The sample was analyzed by secondary ion mass spectrometry. About 1 microgram of glycosphingolipid subjected to TLC can be analyzed. The major advantage of this method is that glycosphingolipid can be analyzed structurally without purification by repeated column chromatography. PMID- 7778784 TI - Effect of beta-mercaptoethanol on the detection of biotinylated proteins. AB - Biotinylated proteins were visualized by enhanced chemiluminescence (ECL) or conventional autoradiography following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and protein transfer onto nitrocellulose. Soaking polyacrylamide gels run under nonreducing conditions in beta-mercaptoethanol (2-ME) prior to protein transfer onto nitrocellulose resulted in a 2- to 10-fold augmentation of the resultant signal. This enhancement was observed for both disulfide- and nondisulfide-bonded proteins. Furthermore, 2-ME had no effect on either the activity of the extravidin-horse-radish peroxidase conjugate, used to detect biotin moieties, or the net protein transfer onto nitrocellulose. Thus, we propose that amplification of either ECL or gamma emission following 2-ME treatment is due to its ability to modify protein conformation, which in turn provides greater access of avidin to biotin. PMID- 7778785 TI - Prediction of protein secondary structure from circular dichroism spectra: an attempt to solve the problem of the best-fitting reference protein subsets. AB - In least-squares fitting of protein circular dichroism (CD) spectra using basis CD spectra for the respective secondary structure components, as given by reference proteins of known structural composition, good fits of the CD spectrum do not necessarily correspond to appropriate fits of the underlying structural composition of a test protein. In an attempt to overcome this problem, CD similarity measures were used to construct a subset of five reference CD spectra which permitted three-component fitting of the CD and prediction of the relative magnitude of total beta-sheet (antiparallel + parallel) and total other structure (beta-turn + remainder), relative to helix, in the test protein. A backpropagation neural network (BPN) was also trained to make this prediction. In subsequent five-component fitting of the CD spectrum, using a Monte Carlo method to generate subsets of reference proteins from the working data set, only those secondary structure fits which conformed to the consensus prediction of the CD similarity measures and the BPN were accepted. The method enhanced the fitting of antiparallel beta-sheet and beta-turn for 16 proteins, compared to the variable selection method of P. Manavalan and W. C. Johnson (1987, Anal. Biochem. 167, 76 85). Some other proteins were less well fitted. Improvement in results is expected with a larger representation of feasible basis CD spectra in the working reference proteins. PMID- 7778786 TI - Simple and efficient method for isolation and measurement of cyanobacterial hepatotoxins by plant tests (Sinapis alba L.). AB - A simple and cost-effective method for isolating and assaying microcystins, cyanobacterial toxins, by C-18 cartridges, DEAE-cellulose (DE-52) chromatography, and a mustard (Sinapis alba L.) plant seedling test is described. The procedure results in a purity of up to 95-97% microcystin without the need for an HPLC system and justifies the use of the S. alba L. seedling test in the quantitative assessment of the toxin with an IC50 of 3 micrograms ml-1 instead of the mouse intraperitoneal test. PMID- 7778787 TI - A fluorescence assay for geranylgeranyl transferase type I. AB - A new fluorescence assay for measuring the activity of geranylgeranyl transferase (type I) is described. It does not require the use of either radiolabeled geranylgeranyl diphosphate or the purified recombinant Ras protein substrate with the carboxy terminal sequence of CVLL. Dansyl GCVLL and unlabeled geranylgeranyl diphosphate are used as substrates. The Km for Dansyl GCVLL and for geranylgeranyl diphosphate is 5 microM and 800 nM, respectively. At equimolar concentrations, enzymatic activity is higher when Dansyl GCVLL is used as a substrate compared to Dansyl GCVII. Dansyl GCVLS, a substrate for farnesyl transferase, is inactive in this assay. CVFL is a competitive inhibitor of geranylgeranyl transferase and exhibits a Ki of 200 nM. PMID- 7778788 TI - A microtiter plate assay using cascade amplification for detection of nonisotopically labeled DNA. AB - We describe a microtiter-plate-based, colorimetric assay for DNA, the enzyme linked DNA-enzyme-linked coagulation assay (EDNA-ELCA). The EDNA-ELCA uses amplification of the common pathway of coagulation for the ultrasensitive detection of DNA which is tagged by incorporation of functional groups such as biotin and fluorescein. The EDNA-ELCA enables detection of attomole amounts of DNA (< 1 pg per microtiter well), with a sensitivity 200-1000 times higher than other colorimetric techniques. The assay has been applied as an adjunct to PCR for quantitative determination of methicillin-resistant Staphylococcus aureus DNA at levels corresponding to 1-10(5) organisms. The EDNA-ELCA can also be used to assay DNA by hybridization; < 50 amol of an unlabeled DNA template is detected by hybridization to biotin- and fluorescein-labeled probes. PMID- 7778789 TI - Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. AB - A method based on isotope dilution-mass spectrometry was developed for the determination of nine cholesterol oxidation products in human plasma. The cholesterol oxidation products determined were cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol (7 alpha- and 7 beta-hydroxycholesterol, respectively), 3 beta-hydroxycholest-5-en-7-one(7-oxocholesterol),5,6 alpha-epoxy 5 alpha- cholestan-3 beta-ol (cholesterol-5 alpha,6 alpha-epoxide),5,6 beta-epoxy 5 beta-cholestan-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), (cholesterol-5 beta,6 beta-epoxide), cholestane-3 beta,5 alpha,6 beta-triol, cholest-5-ene-3 beta,24-diol (24-hydroxycholesterol), cholest-5-ene-3 beta,25-diol (25 hydroxycholesterol), and cholest-5-ene-3 beta,27-diol (27-hydroxycholesterol). A corresponding deuterium-labeled internal standard, containing 3 to 6 deuterium atoms, was synthesized for each cholesterol oxidation product except 5 beta,6 beta-epoxycholesterol which was determined using the internal standard for 5 alpha,6 alpha-epoxycholesterol. Plasma from 31 healthy volunteers was analyzed by the new method and 27-, 24-, and 7 alpha-hydroxycholesterol were the most abundant cholesterol oxidation products (mean values 154, 64, and 43 ng/ml, respectively). The other oxysterols determined were present in concentrations lower than 30 ng/ml. Males had higher 27-hydroxycholesterol concentrations in plasma than females. The 5,6-oxygenated products were present mainly unesterified while the other oxidation products were mostly in esterified form. PMID- 7778791 TI - Alternative methods of preparing whole-cell DNA from fungi for dot-blot, restriction analysis, and colony filter hybridization. AB - There is a large and increasing number of methods for preparing whole-cell DNA from fungi. Modifications have evolved for two reasons. This first is to simplify the protocol as much as possible to allow processing of large sample numbers, in some cases for very specific uses, e.g., dot-blots. The second is to increase the quality of the DNA. Most preparations are contaminated with varying amounts of polysaccharides and unknown wall contaminants that can inhibit subsequent restriction or ligation. The extent of contamination varies with the species, the individual isolate, and at least in Neurospora, with the method or extent of growth. This paper offers three new methods. The first is a simplified procedure for isolating denatured DNAs from filamentous fungi for dot-blot analysis. The second is a rapid method for isolating DNAs from large numbers of small- to medium-scale cultures of filamentous fungi. These preparations are sufficiently pure for a variety of enzymatic reactions. The third is a nonenzymatic method for yeast colony filter hybridization that is simple, inexpensive, and efficient and results in uniform signals for a variety of species. PMID- 7778790 TI - Codelivery to mammalian cells of a transcriptional factor with cis-acting element using cationic liposomes. AB - The human immunodeficiency virus-1 transactivator protein (tat) was codelivered efficiently with a reporter gene under the control of a tat-responsive DNA element using different formulations of cationic liposomes. Expression of a tat responsive reporter gene was induced by incubating cells with a mixture of purified recombinant tat protein, reporter DNA, and liposomes. Different cell lines were tested successfully as targets for the codelivery. Tat was shown to trans-activate the codelivered virus promoter specifically in the cells tested. Codelivery of tat with DNA is a useful model for studying the function of trans acting factors and their cis-acting DNA elements. The currently available methods such as foot-printing only reveal the binding, but not the functional consequence of the binding, of the factor with the element. In addition, this system may prove useful as a model for high level and regulated transgene expression in target cells. PMID- 7778793 TI - [Antibiotic prophylaxis in a surgical setting]. PMID- 7778792 TI - [Antibiotic prophylaxis in the surgical setting. Consensus development conference. Paris, 11-12 December 1992]. PMID- 7778794 TI - [General principles of choice of antibiotics for antibiotic prophylaxis in surgery]. AB - A large amount of knowledge has been obtained in the field of prophylactic antibiotics over the past few years. Only procedures with a reasonable risk (incidence or severity) ought to be covered. Antibiotics must be present not only in plasma but also in the tissues during the surgical procedure. In most cases a very short prophylaxis, usually using a single bolus, is convenient. The best cost/benefit ratio has to be obtained. Several points remain unclear and require further investigations: what is the best dosage? What is the adequate timing for reinjections according to the duration of surgical procedure, and to the risk of postoperative infection using a "risk index"? Must we modulate the type of prophylaxis according to the duration of hospital stay before surgery? What is the value of selective decontamination of the digestive tract? PMID- 7778795 TI - [Antibiotic prophylaxis in ORL surgery and oral medicine]. AB - Postsurgical infection has always been a cause for major concern in ENT surgery. Papers on the topic allowed to identify indications for antibiotic prophylaxis. In ear surgery, in the absence of prior infection (stapes surgery, medium dry ear surgery), studies' results are not in favour of antibiotic prophylaxis. On the other hand, however, when the ear is inflamed or infected, the use of antibiotics is indicated, if possible after having first taken a sample. For nose and sinus surgery, antibiotic prophylaxis seems to be worthless in the absence of a prolonged packing. If a packing has to be maintained or if a transplant is used, an antibiotic administration has to be considered; the most appropriate antibiotic and its mode of use still have to be specified. In case of facial trauma, antibiotic prophylaxis using cefazolin reduces the risk of infection of paraymphysis fractures and angle fractures. The postoperative course after tonsillectomy is simplified by a prolonged antibiotic administration based on ampicillin. In clean cervico-facial surgery, without buccopharyngeal opening, the antibiotic prophylaxis seems to be worthless. In the opposite, antibiotherapy is required in case of buccopharyngeal opening. Indeed the presence of potential pathogenic bacteria in the buccopharyngeal cavity, the difficulties of mucosa closing, the importance of the tumoral extension, the length of the procedure, radiotherapy and use of myocutaneous flaps may all be the cause of a high infection rate (80%) in the absence of antibiotic prophylaxis. Two types of antibiotics seem to be suitable, cefazolin and clindamycin. Antibiotics active against Gram negative bacteria seem to be useless. There is a disagreement concerning the duration of antibiotic administration. The populations studied are too small to obtain significant results. Both points of view (prolonged antibiotic administration or true antibiotic prophylaxis) can be considered. Only large scale prospective studies with an adequate methodology will provide credible data for this debate. PMID- 7778796 TI - [Antibiotic prophylaxis in urology. Surgical and endoscopic surgery. Lithotripsy. Transplantation]. AB - The opening of the urinary tract switches surgical and endoscopic urology to the clean contaminated category and therefore for each of them antibiotic prophylaxis has to be considered. Prophylactic antibiotics are only recommended before surgery in patients with sterile urine. Those with infected urine should have curative antibiotics. Prophylactic antibiotics are commonly recommended for transurethral resection of the prostate, transrectal biopsy of the prostate, renal transplant and radical cystectomy with ileal or colonic pouch for urinary diversion. It is worthless in diagnostic cystoscopy. ESWL and scrotal surgery. For other procedures more data are required to conclude. PMID- 7778797 TI - [Antibiotic prophylaxis in gynecologic surgery]. AB - Hysterectomies are contaminated procedures; surgical wound related sepsis ranges from 10 to 25%. Several randomised controlled studies demonstrated a significant benefit with prophylactic antibiotics. The study results were more controversial for abdominal hysterectomies. Ureidopenicillins, cephamycins and other antibacterial agents active on Gram negative rods and anaerobes can be recommended as a preoperative flash at anaesthesia induction, followed by a second injection whenever the procedure duration exceeds 3 hours. In case of extended hysterectomy for cancer, broad spectrum antibiotic prophylaxis is usual; some recent studies demonstrated the efficacy of a short duration antibacterial agent use. Mastectomies are at low risk for postoperative infection. Antibacterial prophylaxis is common, especially in plastic surgery. PMID- 7778798 TI - [Antibiotic prophylaxis in cesarean section and voluntary termination in pregnancy]. AB - Infection is the main complication after voluntary termination of pregnancy through vacuum aspiration, with an infection rate of 3.6% in the subsequent three weeks. This rate is comparable to that observed in the so-called clean surgical procedures. However the consequences on fertility remain unknown. Studies using systematic antibiotic administration in all vacuum aspirations (voluntary termination of pregnancy and spontaneous abortion) demonstrated the value of such a preventive measure. Factors of risk are difficult to identify and systematic bacteriological specimen collection in all patients undergoing a termination of pregnancy is quite impossible to do. Therefore, the best strategy consists in the oral administration of 200 mg of doxycycline before the aspiration and 200 mg 12 hours later. The incidence of operative-site infection and endometritis after Caesarean section without perioperative antimicrobial prophylaxis varies from 5 to 85%. A variety of risk factors have been identified such as low social category, rupture of membranes, the number of vaginal examinations, labour, and emergency sections. Most clinical trials have shown no significant difference in the efficacy of various antibiotic regimens. However, prophylactic antibiotics decrease significantly the rate of infections. We recommend one or three doses of intravenous prophylactic antibiotic, after clamping and section of the umbilical cord in high risk patients. Cephalosporin of 1st or 2nd generation or ampicillin associated with an inhibitor of beta-lactamases are recommended. PMID- 7778799 TI - [Antibiotic prophylaxis in gastroduodenal surgery]. AB - The incidence of postoperative wound infections is increased up to 35% after gastroduodenal surgery, when gastric motility and acidity are decreased, as in case of gastric ulcer or cancer, obstruction, bleeding, antacid therapy. The endogenous flora contaminating the operative-site consists of organisms of the oropharynx and the jejunum and includes anaerobes like bacteroides, aerobes like streptococci, staphylococci, E. coli. Antimicrobial prophylaxis is therefore indicated in these high risk patients. All groups of antibiotics have been used, however 1st and 2nd generation cephalosporins are the most effective. A single dose given intravenously just before anaesthesia is recommended, a second dose is advisable intraoperatively when surgery is prolonged or massive blood loss occurs. Antibiotic prophylaxis is also recommended in gastric bypass surgery for obesity, but remains controversial for percutaneous endoscopic gastrotomy. PMID- 7778800 TI - [Antibiotic prophylaxis in hepatobiliary surgery]. AB - Today, hepatic and biliary surgery includes conventional biliary surgery, laparoscopic surgery, interventional radiology, endoscopy and hepatic resection surgery. In conventional biliary surgery, the benefit of antibiotic prophylaxis has been demonstrated. Among the risk factors, some are specific (age > 65 years, gallstones in the common bile duct with or without jaundice, history of acute cholecystitis or of biliary surgery) and the others are non specific such as the CDC new index risk (for scoring from 0 to 3, wound infection rates are respectively 1.36, 2.01, 7.11, 11.54%). The targets for antibiotics used in conventional biliary surgery are E. coli, Klebsiella and Streptococcus. In biliary laparoscopic surgery, the rate of infectious complications and results of antibiotic prophylaxis have not been assessed. However, in laparoscopic surgery, the use of an antibiotic prophylaxis similar to that employed in conventional biliary surgery seems logical. In interventional radiology and endoscopy, the modalities and the benefit of antibiotic prophylaxis have not yet been assessed. Infections (angio-cholecystitis) secondary to these procedures are frequent and severe. They are due to multiresistant hospital microorganisms. Antibiotic prophylaxis regimens for hepatic resections have not yet been assessed and are the same as for conventional biliary surgery. PMID- 7778801 TI - [Criteria of validity of studies on antibiotic prophylaxis]. PMID- 7778802 TI - [Antibiotic prophylaxis in colorectal surgery]. AB - In elective colorectal surgery, the benefit of preoperative antibiotic prophylaxis is well established, with a reduction in wound infection rate to less than 10%. The antimicrobial agent used has to be active against aerobic and anaerobic pathogens such as Escheria coli and Bacteriodes fragilis. The efficacy of three schemes of administration: oral and/or parenteral prophylaxis associated with a mechanical preparation, has been demonstrated. Oral antibiotic administration is current practice in USA; the most widely used oral regimen is the combination of erythromycin and neomycin given the day before surgery. Parenteral prophylaxis with a cephalosporin active against Bacteriodes fragilis such as cefoxitin and cefotetan, is preferred in Europe. The issue of whether a systemic prophylaxis should be added to the oral regimen or not has not yet been resolved. However it seems that the association should be proposed in various situations: patients with a high risk factors score (rectal resection and operations lasting more than three hours), patients with incomplete mechanical preparation, delay of the onset of surgery after the last oral dose. PMID- 7778803 TI - [Antibiotic prophylaxis and appendectomy]. AB - Analysis of clinical studies shows that a single preoperative systematic administration of antibiotics may reduce postoperative sepsis rate after appendicectomy. If the appendix is gangrenous or perforated, this therapy must last for a longer time and is not considered as a prophylaxis. In clinical practice, there are obvious advantages in the use of a single agent efficient against both aerobes and anaerobes. According to the literature, cefotetan or cefoxitin (2 g in adults, 40 mg.kg-1 in children) can be proposed. PMID- 7778804 TI - [Antibiotic prophylaxis of penetrating injuries of the abdomen]. AB - Antibiotic prophylaxis for a penetrating injury of the abdomen has a distinctive feature as contamination occurs before administration of antibiotics and because important blood loss can modify the pharmacokinetics of antibiotics. Due to the rate and severity of infectious complications, no controlled study has been undertaken. All authors agree to use prophylactic antibiotics in patients with penetrating injury of the abdomen. Various antibiotic regimens have been administered, but it seems that those using an antibiotic active against anaerobes are more efficient to prevent postoperative infectious complications than without them. There is no benefit to administer antibiotics for more than 24 hours. PMID- 7778805 TI - [Antibiotic prophylaxis in surgery of the esophagus]. AB - Surgery of oesophagus carcinoma is a long and major procedure. Perioperative radiochemotherapy is often required. Therefore many factors favour the occurrence of local and general postoperative infection, justifying an antibiotic prophylaxis directed against oesophageal and gastric flora. In case of oesophageal stenosis, the oesophageal floral often switches to the fecal type. Antimicrobial agents diffuse to the surgical site and reach there high concentrations for the time of surgery. We recommend, just prior the induction of anaesthesia the intravenous administration of a single dose of a third generation cephalosporin (ceftriaxone 2 g) and nitroimidazole (ornidazole 1 g). The long half-life of these agents allows sufficient concentrations at surgical site to be obtained and the efficacy of this regimen has been demonstrated. Selective decontamination of the digestive tract with systemic antibiotherapy is another approach for the prevention of postoperative complications of surgery of oesophagus carcinoma. PMID- 7778806 TI - [Antibiotic prophylaxis in digestive endoscopy]. AB - The increasing use of endoscopy in diseases of the digestive tract has been associated with an increase in complications related to is technique. Because of this, various authors have recommended the administration of prophylactic antibiotics in an attempt to avoid infectious complications. This attitude has however been largely empirical, without a real assessment of the benefits and disadvantages. Although no prospective study has shown any clear benefit, it is generally accepted that prophylactic antibiotics should be given systematically whenever a digestive endoscopy is to be performed in a patient with a cardiac valvular disease or a history of bacterial endocarditis. Apart from these situations, prophylactic antibiotics may be indicated for sclerotherapy of actively bleeding oesophageal varices and prior to colonoscopy in immunodepressed patients or in those with an inflammatory disease of the colon. PMID- 7778807 TI - [The role of new molecules in surgical antibiotic prophylaxis]. AB - The preoperative administration of a new antibiotic for antimicrobial prophylaxis is questionable because of the methodological difficulties to demonstrate its efficiency and benefits in decreasing the postoperative infectious complications. As their rate is very low, especially in clean surgery, the number of patients to be included in a comparative trial is very high. Most studies assessed only small groups and therefore any extrapolation for clinical practice is of limited value. Because of their therapeutic efficiency the fluoroquinolones are often recommended for antimicrobial prophylaxis. However, the rapid occurrence of resistances, directly related to their prescription should invite the prescribers to be cautions. They should be contra-indicated as long as an alternative of similar efficiency is existing, in case of bacteraemia, when an administration of more than 48 hours in required or when the intra-hospital resistance rate exceeds 10 p. 100. PMID- 7778808 TI - [Surgical antibiotic prophylaxis in a patient undergoing immunosuppressive treatment]. PMID- 7778809 TI - [Economic aspects of surgical antibiotic prophylaxis]. AB - The cost of an antibiotic is easily evaluated in the case of antimicrobial prophylaxis. The other expenses, either direct or indirect costs, are much more difficult to assess. Studies evaluating the economical impact of the prophylactic antibiotics are rather rare. Antibiotic prescription for prophylaxis is evaluated to represent about 20 to 30% of the total antibiotic administration in French hospitals. The most significant studies evaluate the cost/benefit ratio and demonstrate the advantage of prophylaxis in orthopaedic, vascular and gynaecologic surgery. PMID- 7778810 TI - [Microbiologic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery]. AB - The choice of an antibiotic for antimicrobial prophylaxis is based on microbiological, pharmacokinetic, chemical and pharmacodynamic parameters. The knowledge of the bacterial flora allows the identification of bacteria which could be responsible for postsurgical infections. These floras are complex and their equilibrium can be modified by various factors, such as hospitalization, co existing disease, medico-surgical procedure, administration of antibiotics, which cause the selection of the so-called hospital-bacteria feared by therapists. The infection will develop according to the quantity of bacteria that have been introduced and to their virulence, which is often altered by local factors, especially the biomaterials. The knowledge of pharmacodynamic parameters such as bactericidal activity, postantibiotic effect, activity on virulence factors (bacterial adhesion), allows the refinement of the choice of the antibiotic and the optimization of its posology. PMID- 7778811 TI - [Pharmacokinetic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery]. AB - The prevention of surgical infections with perioperative prophylactic antibiotics is experimentally and clinically well founded in both principle and practice. The evaluation of the role of antimicrobial agents in the success of failure of infection prophylaxis in surgery involves a discussion of both the pharmacokinetic and the pharmacodynamic properties of particular agents. A main concern in surgical prophylaxis is the relation between the respective time course of antibiotic concentrations in serum and in the tissue (wound). Several problems arise in both the measurement and the interpretation of drug concentrations in tissues and the results of this approach are still controversial. However, the knowledge of the numerous factors influencing the penetration into a tissue and the characteristics of the relative distribution of the antibiotic between the compartments inside the tissue, i.e. the vascular, interstitial and intracellular spaces, could allow a valuable approach to this problem. The concentrations of free drugs in serum are valuable predictors of the time course of unbound drug in interstitial fluid, where the bacteria are generally located. An increase in protein binding does not reduce the area under the curve (AUC) of free drug for beta lactam agents eliminated predominantly by glomerular filtration, but prolongs their elimination half life. Timing and route of administration are also important factors to consider in relation with the pharmacokinetic profile of the drug. Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period during which the free drug concentration exceeds the MIC is an important parameter of the efficacy of beta lactam antibiotics. In the opposite, the Cmax and/or the AUC are the major parameters of the efficacy of aminoglycosides and quinolones against Gram negative bacteria. Thus, the goal of prophylaxis with beta lactams could be to provide levels of free drug above the MIC for the whole surgical period, while the obtention of a high Cmax with a one-day therapy should be required for aminoglycosides. Further clinical trials are warranted to assess this approach. PMID- 7778812 TI - [Impact of antibiotic prophylaxis on microbial ecology]. AB - This review of the literature analysed the impact of prophylactic antibiotics on patients, nurses, the ecosystem of the wards, the hospital and the general environment. After prophylactic antibiotics a qualitative and quantitative modification of the cutaneous and digestive flora of the patient can occur, as well as modification of susceptibility to antibiotics. Several factors may modulate their action on the bacterial flora: the breadth of the spectrum, the administered dose, the duration of treatment, the form of development of resistance and the type of antibiotics. Numerous studies have demonstrated the role of the nursing staff as a reservoir of multi-resistant micro-organisms. Staff of intensive care units is apparently the most affected. Prophylactic antibiotics can also induce changes in the quantitative and qualitative features both in the ward and hospital flora. An increase in the bacterial resistance to antibiotics in the general environment can occur; a long duration of oral prophylactic antibiotic administration is undoubtedly associated with this phenomenon. Thus, the benefit associated with prophylactic antibiotic in the prevention of postoperative infections, unquestionable in some indications, must be balanced with the possible selection of resistant micro-organisms and their consequences on the environment. PMID- 7778813 TI - [Antibiotic prophylaxis in orthopedic surgery]. AB - The efficiency of prophylactic antibiotics in total hip replacement has been demonstrated by several studies. The rate of infection decreased approximatively from 3% to 1% with a cephalosporine 1 protocol. The rate of infection was not different after a five-day administration of cephalosporine 1 and a 2-day treatment of cephalosporine 2. In open fractures, the value of prophylactic antibiotics has to take in account the usual organisms of peroperative contamination as well as the anaerobes. Short administration can be used, however no randomized studies have proven their efficiency. For clean, planned surgery (grade II in the classification of Health National Research Council), prophylactic antibiotics seem to be of value. However, the prescription should not be systematic, but correlated with the local conditions of surgery and the infection rate of the type of the planned procedure. PMID- 7778814 TI - [Antibiotic prophylaxis in multiple trauma patients]. AB - Infection prophylaxis in multiple trauma patients includes prophylaxis of infections due to surgery, which is the true one as well as the prophylaxis of secondary acquired infections which are more frequent, especially in case of co existing shock. The association an aminopenicillin with a beta-lactamase inhibitor is recommended for prophylaxis of surgical infections. These antibiotics need to be administered early and in high doses, as the pharmacokinetic parameters are modified in trauma patients, with an increased volume of distribution and a shortened half-life of elimination. Prevention of secondary infection relies on a medico-surgical treatment of haemorrhagic shock. Other preventive measures, such as early enteral nutrition, selective decontamination of the digestive tract and immunotherapy, still need to prove their efficacy. PMID- 7778815 TI - [Prevention of infectious endocarditis]. AB - An antibiotic prophylaxis of infective endocarditis is recommended in patients at high risk for infective endocarditis (patients with valvular prosthesis, or cyanogen congenital or obstructive cardiac defect) or those with aortic, mitral or tricuspid valvulopathy, a non-cyanogen congenital or obstructive cardiac defect. Dental procedures (except treatment for superficial decay and preparation for the fitting of prostheses to teeth with intact pulp) are to be carried out under local antisepsis and a prophylactic antibiotics, such as 3 g of oral amoxicillin or in case of allergy to penicillin, 600 mg of clindamycin or 1g of pristinamycin, administered one hour prior to the procedure. A similar prophylaxis is recommended for the procedures on the upper respiratory tract. Amoxicillin, or vancomycin or teicoplanin are recommended for procedures under general anaesthesia. For surgery on the intestinal or urogenital tract, regimens combine amoxicillin with gentamicin, or in case of allergy to penicillin, vancomycin or teicoplanin with gentamicin. PMID- 7778816 TI - [Antibiotic prophylaxis in thoracic surgery, pulmonary endoscopy, thoracic injuries and lung transplantation]. AB - Effectiveness of prophylactic antibiotics is at present time well documented for many surgical procedures. In lung surgery, numerous randomized double-blinded studies have demonstrated the effectiveness of 1st or 2nd generation cephalosporins, administered over a short period of time, not exceeding 24 h. In the opposite, thoracic injuries do not seem to require prophylactic antibiotics, except penetrating injuries of the chest, which could benefit from a single antibiotic injection. In case of lung transplantation, infectious complications result from many factors, among which immunosuppression plays an important role. A prolonged antibiotherapy is routinely used by many transplantation teams, despite the lack of studies proving the effectiveness of this practice. PMID- 7778817 TI - [Antibiotic prophylaxis in heart surgery]. AB - Cardiac surgery enters mainly into the class I of Altemeier ("clean surgery"). However, many factors may explain an intraoperative contamination: surgery of long duration, extra-corporeal circulation, aspiration of blood and air, immunodepression...). In fact, the infectious risk decreases from about 25% with placebo to 5% with prophylactic antibiotics. The staphylococcal infections are the most frequent (mediastinitis, endocarditis, parietal infections...). Cephalosporins, particularly of second-generation type (cefamandole, cefuroxime), perform better than antistaphylococcal penicillins. The combination with an amino side may be used when Gram negative bacilli infection prevalence is high. Vancomycin is efficient but hypotension and renal impairment have been reported. Therefore, vancomycin is used in patients allergic to cephalosporins, when a high prevalence of methicillin-resistant Staphylococcus or enterococci infections is reported, or when the patient has recently received broad-spectrum antimicrobial therapy. The antibiotic doses must take into account the haemodilution due to extracorporeal circulation and the necessity to obtain sufficient serum concentrations throughout surgery. A prophylaxis of more than 48 hours is not associated with an improved outcome. In cardiac transplantation a prophylaxis is essential, but is still questioned during the insertion of pace-markers. In any case, the antibiotic prophylaxis must take into account the bacterial prevalence of each institution. PMID- 7778819 TI - [Antibiotic prophylaxis in neurosurgery]. AB - Postoperative wound infections are a serious complication in neurosurgery. The average infection rate without antibiotics ranges between 5-11% in CSF shunts, between 2-5% in craniotomies and spinal surgery in clean and clean contaminated patients, and 11-38% in CSF fistulas. In CSF shunt procedures as well as in craniotomies, common skin commensals, mainly coagulase negative and positive staphylococci are responsible for most postoperative infections. Contradictory results of the studies evaluating the efficacy of prophylactic antibiotics (PA) make it impossible to conclude whether antibiotics have any impact on the incidence of infections or not. Nevertheless the decision to use PA must be left to each surgeon and based on own experience (the mean rate of infection decreased from 5-11% to 1% with PA in France). In clean and clean contaminated surgery, the weight of evidence based on some large, prospective, randomized studies, suggests that PA exerts a protective effect, for which an antistaphylococci antibiotic would be appropriate. In case of methi-R organisms, a second generation cephalosporin is an alternative. Association of vancomycin-gentamicin is not recommended routinely because of the risk of development of resistance. PMID- 7778818 TI - [Antibiotic prophylaxis in vascular surgery]. AB - Vascular surgery includes various surgical procedures and sites. Infectious risk is low but with a high functional risk and a high mortality rate. Infection risk factors are numerous. Among them the incision in the Scarpa's triangle is at the first place. Antimicrobial prophylaxis in vascular surgery has shown its efficacy whatever the agent. The second generation cephalosporins are the most logical, with a duration of administration of less than 24 hours. In case of re-operation glycopeptides have shown their efficacy. PMID- 7778820 TI - [Prophylactic antibiotic therapy in ocular surgery]. AB - Prophylactic antibiotics have been used by ophthalmic surgeons routinely before and after surgery. However, the optimal type of antibiotics and route of administration have not yet been clearly established. In this article, ocular surgery patterns, bacteriology and pharmacokinetics of antibiotics within the eye are reviewed, to try to provide rationale for antimicrobial prophylaxis. PMID- 7778822 TI - Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis. AB - OBJECTIVE: To determine if nitric oxide output in exhaled air is increased in patients with liver cirrhosis. DESIGN: Cross-sectional study. SETTING: A university hospital. PATIENTS: 50 patients with liver cirrhosis, 6 patients with chronic hepatitis, and 15 healthy controls. MEASUREMENTS: Nitric oxide in exhaled air was measured using a chemiluminescence analyzer. Cardiac index was determined using echocardiography. RESULTS: Patients with decompensated liver cirrhosis had higher levels of exhaled nitric oxide output (Child C patients, 190 +/- 11 nL/min per m2 body surface area) than controls (97 +/- 8 nL/min per m2 body surface area; P < 0.001), whereas patients with compensated liver cirrhosis or chronic hepatitis had levels of nitric oxide output similar to those found in controls. Cardiac index was greater in patients with liver cirrhosis (Child C patients, 4.3 +/- 0.3 L/min per m2 body surface area) than in controls (2.9 +/- 0.2 L/min per m2 body surface area; P < 0.001). Cardiac index correlated with nitric oxide levels (r = 0.621; P < 0.001). CONCLUSIONS: Increased nitric oxide output in exhaled air is associated with systemic circulatory disturbances in patients with liver cirrhosis. PMID- 7778821 TI - Plasma metanephrines in the diagnosis of pheochromocytoma. AB - OBJECTIVE: To examine whether tests for plasma metanephrines, the o-methylated metabolites of catecholamines, offer advantages for diagnosis of a pheochromocytoma over standard tests for plasma catecholamines or urinary metanephrines. DESIGN: Cross-sectional study. SETTING: 3 clinical specialist centers. PATIENTS: 52 patients with a pheochromocytoma; 67 normotensive persons and 51 patients with essential hypertension who provided reference values; and 23 patients with secondary hypertension and 50 patients with either heart failure or angina pectoris who served as comparison groups. MEASUREMENTS: Plasma concentrations of catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrine and metanephrine) were measured in all patients. The 24-hour urinary excretion of metanephrines was measured in 46 patients with pheochromocytoma. RESULTS: Pheochromocytomas were associated with increases in plasma concentrations of metanephrines that were greater and more consistent than those in plasma catecholamine concentrations. No patient with a pheochromocytoma had normal plasma concentrations of both normetanephrine and metanephrine. The sensitivity of these tests was 100% (52 of 52 patients [95% CI, 94% to 100%]), and the negative predictive value of normal plasma concentrations of metanephrines was 100% (162 of 162 patients). Tests for plasma catecholamines yielded eight false-negative results and a sensitivity of 85% (44 of 52 patients [CI, 72% to 93%]). The negative predictive value of normal plasma concentrations of catecholamines was 95% (156 of 164 patients). Tests for urinary metanephrines yielded five false-negative results and a sensitivity of 89% (41 of 46 patients [CI, 76% to 96%]). Because no statistical difference was noted in the number of false-positive results between tests for plasma metanephrines (15%) and tests for plasma catecholamines (18%), the specificities of the two tests did not differ. CONCLUSIONS: Normal plasma concentrations of metanephrines exclude the diagnosis of pheochromocytoma, whereas normal plasma concentrations of catecholamines and normal urinary excretion of metanephrines do not. Tests for plasma metanephrines are more sensitive than tests for plasma catecholamines or urinary metanephrines for the diagnosis of pheochromocytoma. PMID- 7778823 TI - Hemodynamically significant extrinsic left atrial compression by gastric structures in the mediastinum. PMID- 7778824 TI - Cardiovascular problems in pregnant women with the Marfan syndrome. AB - PURPOSE: To review the available information on the diagnostic, prognostic, and therapeutic aspects of cardiac complications in women with the Marfan syndrome during the peripartum period and to develop guidelines for the approach to these patients on the basis of this information. DATA SOURCES: A MEDLINE search and a manual search of bibliographies from reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Articles that reported on pregnancy in patients with the Marfan syndrome or that discussed potentially relevant aspects of the syndrome. RESULTS: Pregnancy in the Marfan syndrome is associated with two primary problems: potential catastrophic aortic dissection and the risk for having a child with the syndrome. The risk for peripartum aortic dissection is especially high in women in whom aortic root dilatation is diagnosed before pregnancy. Gestation seems to be safer in women without preexisting cardiovascular disease; however, an event free pregnancy cannot be guaranteed. The Marfan syndrome is inherited in an autosomal dominant manner, and the fetus has a 50% risk for inheriting the mutant gene. CONCLUSIONS: Women with the syndrome should be counseled before conception about the risks of pregnancy to both mother and fetus. Because preconceptual dilatation of the ascending aorta seems to be an important predictor for aortic dissection, it should be excluded before pregnancy. Transesophageal echocardiography seems to be preferable for noninvasive assessment of aortic dilatation before and during pregnancy. Prophylactic use of beta-blockers may be useful in preventing aortic dilatation. Surgery should be considered during gestation in patients with progressive aortic dilatation when or before the aortic root reaches 5.5 cm. Because of the potential risk of ionizing radiation to the fetus, noninvasive methods such as transesophageal echocardiography and magnetic resonance imaging are preferred to contrast aortography for the diagnosis of aortic dissection during pregnancy. Vaginal delivery can be done in patients with the Marfan syndrome who do not have cardiovascular system abnormalities. In patients with aortic dilatation, aortic dissection, or other important cardiac abnormalities, cesarean section should be the preferred method of delivery. PMID- 7778825 TI - Medical resources on the Internet. AB - Advances in telecommunications technology in the last decade have fostered the development of computer networks that allow access to vast amounts of information and services. Of the many computer networks that have been developed, the most prominent is the Internet. Originally intended to be a way to share computing resources among academic and research institutions in the United States, the Internet has gradually evolved into a worldwide network of computers that provides various services reflecting the eclectic nature of its component networks. The recent upsurge in interest in the Internet is due to several mutually reinforcing factors: increased ease and availability of access to the Internet, lower access charges, faster communications, and more organizations offering commercial and noncommercial services over the Internet. Of particular interest to the medical community is the large and increasing number of technical, scientific, and biomedical resources that can be accessed through the Internet. Most large medical centers have publicly accessible information, and some large organizations, such as the National Institutes of Health, have extensive databases and services that can be used by medical researchers, clinicians, and educators. In addition, many medical organizations and some medical journals are advertising their services over the Internet and can be contacted through electronic mail. As the cost of telecommunications decreases and the speed of telecommunications increases, new forms of computer communication, such as long-distance, real-time audio, and video services will become available. Computer networks in general and the Internet in particular are likely to play more important roles in many aspects of medicine in the future. PMID- 7778826 TI - Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. AB - PURPOSE: To assess the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn disease and the effectiveness of azathioprine in maintaining remission of quiescent disease. DATA SOURCES: Pertinent studies were selected from the MEDLINE database (1966 to May 1994), abstracts from major gastrointestinal meetings, and references from published articles and reviews. STUDY SELECTION: Nine randomized, placebo-controlled trials of azathioprine or 6 mercaptopurine therapy were identified: Four addressed active disease, two addressed quiescent disease, and three had multiple therapeutic arms. DATA EXTRACTION: Data were extracted by three independent observers on the basis of the intention-to-treat principle and were analyzed with logistic regression. Each study was given a quality score on the basis of predetermined criteria. DATA SYNTHESIS: Compared with placebo, azathioprine or 6-mercaptopurine therapy had an odds ratio of response of 3.09 (95% CI, 2.45 to 3.91) in patients with active Crohn disease. When the single trial that used 6-mercaptopurine in active disease was excluded from the analysis, the odds ratio of response was 1.45 (CI, 1.12 to 1.87). No trials of quiescent disease used 6-mercaptopurine; the odds ratio of response in these trials of quiescent disease was 2.27 (CI, 1.76 to 2.93). For active disease, continuation of therapy for at least 17 weeks improved response (P = 0.03). For quiescent disease, a higher dose improved response (P = 0.008). Increased cumulative dose improved response in both groups (P < 0.001 for active disease and P = 0.01 for quiescent disease). A steroid-sparing effect was seen in active disease (odds ratio, 3.69 (CI, 2.12 to 6.42) and in quiescent disease (odds ratio, 4.64 [CI, 1.00 to 21.54]). Fistulae improved with therapy (odds ratio, 4.44 [CI, 1.50 to 13.20]). Adverse events requiring withdrawal from a trial, primarily allergy, leukopenia, pancreatitis, and nausea, were increased with therapy (odds ratio, 5.26 [CI, 2.20 to 12.60]). CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective in treating active Crohn disease and in maintaining remission. Cumulative dose was an important factor in predicting response. Adverse effects were more common among patients receiving therapy. PMID- 7778827 TI - Esophageal ulceration in human immunodeficiency virus infection. Causes, response to therapy, and long-term outcome. AB - OBJECTIVE: To determine the causes of esophageal ulceration, the response rate to currently available therapies, and the long-term outcome in patients with human immunodeficiency virus (HIV) infection. DESIGN: Prospective cohort study. SETTING: An urban county hospital. PATIENTS: Consecutive patients with HIV infection and endoscopically detected esophageal ulceration during a 4-year period. INTERVENTION: Causes of ulcers were determined from clinical, endoscopic, and pathologic findings. Standard medical therapies for the identified causes were instituted, and ulcer healing was endoscopically confirmed when possible. MEASUREMENTS: Symptomatic and endoscopic response to therapy and long-term outcome, including survival. RESULTS: 100 patients with esophageal ulcer were identified. Ulcers caused by cytomegalovirus alone were the most common (n = 45); idiopathic ulcers were almost as frequent (n = 40). Herpes simplex virus esophagitis alone was identified as a cause in only 5 patients. Several potential causes of ulcer were found in 5 patients, including Candida esophagitis in 27 patients. Ten patients developed more than one cause of ulceration during long term follow-up. Eighty-five patients had specific medical therapy for their identified disorders and had an overall response rate of 98%. Median survival from time of diagnosis was 8.9 months (range, 2 days to > 42 months). A difference in median survival was found between patients with cytomegalovirus esophagitis and those with idiopathic esophageal ulcer (7.6 months compared with 13.1 months; P = 0.03). CONCLUSIONS: Given 1) the broad spectrum of causes of esophageal ulceration, 2) that each of these causes requires specific therapy, and 3) the apparent high response rate, it is important to do endoscopic evaluation with mucosal biopsy in patients with HIV infection so that a diagnosis can be established and appropriate therapy instituted. Despite effective therapy, long-term survival is poor; however, long-term remission and survival may occur in some patients. PMID- 7778828 TI - Searching for pheochromocytoma: a new and better test? PMID- 7778829 TI - Internet-based medical information: time to take charge. PMID- 7778831 TI - Clarithromycin therapy for Mycobacterium avium complex bacteremia. PMID- 7778830 TI - Clarithromycin therapy for Mycobacterium avium complex bacteremia. PMID- 7778832 TI - Treatment of the hypereosinophilic syndrome with interferon-alpha. PMID- 7778833 TI - The future general internist. PMID- 7778835 TI - The future general internist. PMID- 7778834 TI - The future general internist. PMID- 7778836 TI - The future general internist. PMID- 7778837 TI - The future general internist. PMID- 7778838 TI - Revised formula for study meal. PMID- 7778839 TI - Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. AB - OBJECTIVES: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls. DESIGN: Prospective cohort study. SETTING: A health maintenance organization in Seattle, Washington. PARTICIPANTS: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue. MEASUREMENTS: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment. RESULTS: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue. CONCLUSIONS: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100,000 persons. PMID- 7778841 TI - Stool composition in factitial diarrhea: a 6-year experience with stool analysis. AB - OBJECTIVE: To evaluate the utility of stool water analysis in the management of patients with chronic diarrhea. DESIGN: Retrospective analysis of 6 years of experience. SETTING: A specialized laboratory in a major referral center. PATIENTS: 325 patients with diarrhea who were referred for stool chemistry analysis. Fecal analysis was requested by many internists and gastroenterologists. Patient records were reviewed to establish the final and most likely cause of diarrhea. RESULTS: One third of patients provided samples that were inappropriate for analysis, but data from 202 persons were available. The usefulness of the general separation of cases of chronic diarrhea into those in which patients had predominantly osmotic pathophysiologies and those in which patients had predominantly secretory pathophysiologies was confirmed, but overlap and intra-individual variability limited the usefulness of this approach in individual patients. Thirty-five patients (17%) had a diagnosis of factitial diarrhea (30 because of laxative use and 5 because of fluid added to stools). CONCLUSIONS: Among selected subpopulations, the chemical analysis of fresh stools has a role in the evaluation of obscure examples of chronic diarrhea. It is especially useful in identifying factitial diarrhea. PMID- 7778840 TI - Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. AB - OBJECTIVE: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia. DESIGN: A randomized, double-blind, placebo-controlled, multicenter trial. SETTING: 36 centers in the United States, Canada, and Australia. PATIENTS: 419 immunocompetent adults with uncomplicated herpes zoster. INTERVENTION: Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days. MEASUREMENTS: Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study. RESULTS: Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750 mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months. CONCLUSIONS: Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia. PMID- 7778842 TI - Lyme neuroborreliosis. AB - Neuroborreliosis, an infection of the nervous system caused by spirochetes of the genus Borrelia, has achieved worldwide attention in the last decade as part of the clinical spectrum of Lyme disease. This disorder, caused by Borrelia burgdorferi, has increased in incidence to become the most frequent arthropod borne infection in North America and Europe. As a result of this rapid rise in incidence and of its protean neurological manifestations, this disease has created an important challenge to modern neurology. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. This review takes a chronological approach to clinical neuroborreliosis to summarize its most important aspects. The limitations as well as the benefits of laboratory diagnosis are also considered, with the aim of providing assistance in this area. Recent advances in neuroimmunology regarding the pathogenesis of neuroborreliosis that may elucidate its protean clinical spectrum are summarized. PMID- 7778843 TI - Magnetic stimulation over the cerebellum in humans. AB - Magnetic stimulation performed with a double-cone coil placed over appropriate positions on the back of the head reduced the size of electromyographic responses evoked by magnetic cortical stimulation in the first dorsal interosseous muscle when it preceded the cortical stimulus by 5, 6, and 7 msec. No suppression of responses to electrical cortical stimulation occurred. Greater suppression was evoked by stronger cerebellar stimuli; lesser suppression was elicited by stronger cortical stimuli. These physiological findings correspond to those obtained with electrical cerebellar stimulation. The most effective position for magnetic stimulation over the back of the head was slightly rostral to the foramen magnum level on the ipsilateral side of the muscle studied. This indicates that the conditioning stimulus activates certain structures at the back of the head on the ipsilateral side of the muscle, consistent with the cerebellum, because the part of the cerebellum regulating limb muscles is positioned about there on the ipsilateral side. In 2 patients with only cerebellar dysfunction, this suppression effect was not elicited, which also supports that the suppression is caused by activity in cerebellar structures. We conclude that magnetic stimulation over the cerebellum with a double-cone coil elicits the same suppressive effect on the motor cortex as electrical stimulation, but with less discomfort; moreover, we believe that this effect is produced by activation of certain cerebellar structures. PMID- 7778845 TI - Recovery from Wernicke's aphasia: a positron emission tomographic study. AB - Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke. PMID- 7778844 TI - Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson's disease. AB - Following the discovery of inhibition of electron transport complex 1 by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a parkinsonian syndrome in humans, monkeys, and mice, several laboratories have reported abnormalities of complex I and other electron transport complexes (ETCs) in various tissues from patients with Parkinson's disease (PD). Criticism of the significance of these findings in the etiology of PD has centered on whether drug treatments or the debilitation of the disease process itself produced the low ETC activities. We present results from a blinded study of platelet mitochondrial ETC activities in 18 early untreated PD patients and 18 age- and sex-matched controls and in 13 spousal controls. Lower complex I activity in platelet mitochondria of PD patients was seen in early untreated disease and thus cannot be due to debilitation or drug therapy. Home environmental factors seem an unlikely explanation for the reduced complex I activity in PD patients but have not been excluded. Complex II/III activity was also reduced by 20% in PD compared with age /sex-matched controls. The low complex I and II/III activities in platelet mitochondria appear to be related to the etiology of PD. PMID- 7778846 TI - First seizures associated with playing electronic screen games: a community-based study in Great Britain. AB - Active surveillance by virtually all electroencephalographic departments throughout Great Britain identified 118 patients who had a first seizure while playing an electronic screen game during two 3-month periods. Patients were divided into Group A (46 patients)--those for whom there was thought to be a definite causal relationship (type 4 photoparoxysmal response); Group B (25 patients)--those for whom there was a probable causal relationship (types 1-3 photoparoxysmal response, clinical evidence of photosensitivity, subsequent recurrent seizures on repeat exposure to electronic screen games, and/or occipital spikes in the resting electroencephalogram); and Group C (47 patients)- those for whom there was no apparent causal relationship. The number of patients in Group C did not exceed that expected by the chance occurrence of two common events (playing electronic screen games and incidence of epilepsy). Most (103/118) of the patients were in the age range of 7 to 19 years. Within this age group the annual incidence of first seizures triggered by playing electronic screen games (Groups A and B combined) was estimated to be 1.5/100,000. PMID- 7778847 TI - Comparison of ictal SPECT and interictal PET in the presurgical evaluation of temporal lobe epilepsy. AB - We retrospectively compared ictal technetium 99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) and interictal 18F fluorodeoxyglucose positron emission tomography (PET) in 35 patients with well lateralized temporal lobe epilepsy (TLE). Based on SPECT scans the two observers correctly lateralized seizure foci with certainty in 89% of patients; interobserver agreement was excellent. Both observers incorrectly lateralized the seizure focus on two SPECT scans; one error was explained by rapid electroencephalographic spread to the contralateral side and for the other patient, isotope was injected during a brief aura. Based on PET scans, observers correctly lateralized the foci with certainty in 63% and with lesser confidence in 83%; four incorrect lateralizations were made by one observer and none by the other. PET interobserver disagreement was explained by differences between observers in weighting the relative hypometabolism in medial and lateral temporal regions. The detection rate for PET was lower in the absence of structural imaging abnormalities (60 vs 87%). PET yielded correct lateralizations in the 2 patients for whom SPECT interpretation was difficult. We conclude that both ictal SPECT and interictal PET are sensitive methods for the lateralization of TLE, but SPECT can be interpreted with greater certainty and is more sensitive when magnetic resonance imaging findings are negative. False lateralization is rare with ictal SPECT and can be explained when interpreted in conjunction with electroclinical data. Both investigations have complementary roles when localization is difficult. PMID- 7778848 TI - Motor reorganization in acquired hemidystonia. AB - Regional cerebral blood flow (rCBF) was measured with H2(15)O positron emission tomography in 5 patients with acquired hemidystonia (AHD) due to structural lesions of the basal ganglia or posterior thalamus contralateral to the dystonic limb. Patients were scanned at rest and when performing paced joystick movements in freely chosen directions with the dystonic and then the unaffected arm. Findings were compared with those of 5 age-matched controls performing joystick movements with the right arm. At rest, there was decreased activity in ventroanterior thalamus, posterior thalamus, angular gyrus ipsilateral to the lesion, and bilateral frontoorbital cortex. At a similar level of significance, increased resting activity was found in lentiform nucleus, hippocampus, and anterior insula contralateral to the lesion. Using the affected arm, AHD cases showed significant overactivity of contralateral prefrontal, lateral premotor cortex, rostral supplementary motor area, anterior cingulate area 32, bilateral sensorimotor cortex (SMC) and insula, mesial parietal cortex, and ipsilateral cerebellum. There was similar frontal overactivity when the unaffected arm performed the joystick movements, though SMC and insula overactivity was contralateral rather than bilateral. The associated frontal overactivity on movement is consistent with acquired dystonia being a syndrome of thalamofrontal disinhibition due to structural disruption of basal ganglia inhibitory control. Our findings also suggest that cortical activation during movement of the unaffected limb is abnormal in acquired hemidystonia. PMID- 7778849 TI - Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. AB - Heme oxygenase-1 is a cellular stress protein expressed in brain and other tissues in response to oxidative challenge and other noxious stimuli. Using immunohistochemistry and immunofluorescent labeling in conjunction with laser scanning confocal microscopy, we observed intense immunoreactivity of heme oxygenase-1 in neurons of the hippocampus and temporal cortex of Alzheimer diseased (AD) brain relative to age-matched control specimens. Furthermore, we demonstrated consistent colocalization of heme oxygenase-1 to glial fibrillary acidic protein-positive astrocytes, neurofibrillary tangles, and senile plaques in the AD specimens. In AD hippocampus, approximately 86% of glial fibrillary acidic protein-positive astrocytes expressed heme oxygenase-1, whereas only 6.8% of hippocampal astrocytes in normal senescent control specimens were immunopositive for heme oxygenase-1 (p < 0.0001). In regions other than the hippocampus and neocortex, such as the substantia nigra, the proportion of astrocytes expressing heme oxygenase-1 in the experimental group (12.8%) was not significantly different from that in the controls (6.4%, p > 0.05). Robust 32-kd bands corresponding to heme oxygenase-1 were observed by Western blotting of protein extracts derived from AD temporal cortex and hippocampus after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heme oxygenase-1 bands were very faint or absent in protein extracts prepared from control specimens. These results indicate that heme oxygenase-1 is significantly overexpressed in neurons and astrocytes of AD hippocampus and cerebral cortex relative to control brains. Upregulation of heme oxygenase-1 in AD brain supports the contention that the affected tissues are experiencing chronic oxidative stress. In addition, the excessive generation of carbon monoxide, a metabolite of heme degradation, may participate in the pathogenesis of AD. PMID- 7778850 TI - Dentatorubral-pallidoluysian atrophy: clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. AB - Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat effects the clinical manifestations of dentatorubral-pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = -0.696, p < 0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62-79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non-progressive myoclonus epilepsy phenotype showed smaller expansions (54-67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral-pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems. PMID- 7778851 TI - Pallidotomy increases activity of motor association cortex in Parkinson's disease: a positron emission tomographic study. AB - Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas. PMID- 7778852 TI - The vasculopathy of varicella-zoster virus encephalitis. AB - Varicella-zoster virus (VZV) encephalitis has become more prevalent in the era of acquired immunodeficiency syndrome and other immunosuppressive diseases and poses diagnostic and therapeutic challenges for clinicians, radiologists, and pathologists. Six cases studied at our institutions shed light on the patterns and pathogenesis of the disease. VZV encephalitis is predominantly a vasculopathy, involving small and large vessels, that generates seizures, mental changes, and focal deficits. Brain imaging reveals large and small ischemic or hemorrhagic infarcts, often both, of cortex and subcortical gray and white matter. Deep-seated white matter lesions often predominate and are ischemic and/or demyelinative, depending on the size of blood vessels involved and the amount of additional demyelination caused by infection of oligodendrocytes. The demyelinative lesions are smaller and less coalescent than those seen in progressive multifocal leukoencephalopathy. PMID- 7778853 TI - Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease. AB - The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues. PMID- 7778855 TI - Common variable immunodeficiency and inclusion body myositis: a distinct myopathy mediated by natural killer cells. AB - Inclusion body myositis developed in two men, 36 and 48 years old with long standing common variable immunodeficiency. Immunophenotypic analysis of the endomysial cells showed an increased number of natural killer (NK) cells (defined as CD57+, CD56+, CD3-, CD8-, CD68-) accounting for 8.5 to 9.5% of the total cells, compared with a mean of 1% in sporadic inclusion body myositis. The remaining cells were CD8+, macrophages, and CD4+ T cells. NK cells were positive for intercellular cell adhesion molecule-1 and invaded muscle fibers negative for major histocompatibility complex (MHC) class I. In contrast to ubiquitous endomysial expression of MHC class I antigen in sporadic inclusion body myositis, the MHC class I in common variable immunodeficiency and inclusion body myositis was absent or weakly expressed in only some of the muscle fibers surrounded by CD8+ cells. Enteroviral or retroviral RNA sequences were not amplified. Treatment with intravenous immunoglobulin improved strength in 1 patient whose repeated muscle biopsy specimen showed normal NK cells. We conclude that inclusion body myositis can develop in patients with common variable immunodeficiency. Common variable immunodeficiency with inclusion body myositis is an immune myopathy mediated by NK cells in a non-MHC class I-restricted cytotoxicity, and by CD8+ cells in an MHC class I-restricted process. This is the first description of an inflammatory myopathy in which NK cells participate in the myocytotoxic process. PMID- 7778854 TI - Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. AB - Elevated plasma levels of interleukin-6 (IL-6), a key regulator of the acute phase response that includes increased fibrinogen synthesis, have recently been detected in patients with acute stroke. Nevertheless, the role of the acute phase response in stroke has been controversial, with some studies suggesting that preexisting infection accounts for most of the acute phase response. Increased IL 6 could signal the involvement of antiinflammatory activity, since IL-6 stimulates the production of endogenous antiinflammatory mediators such as interleukin-1 receptor antagonist (IL-1RA). To better understand the interaction of pro- and antiinflammatory acute phase processes in brain infarction, plasma levels of IL-1RA, IL-6, and acute phase proteins including fibrinogen and c reactive protein (CRP) were measured within 4 +/- 2 days of onset in 50 patients with acute ischemic stroke and in 20 age-matched healthy controls. After excluding patients with evidence of infection, both IL-1RA and IL-6 were significantly elevated in stoke patients compared with controls (p < 0.0001). IL 1RA and IL-6 were both significantly correlated with levels of CRP, p < 0.05 and p < 0.001, respectively, but not with each other. Levels of IL-6 and IL-1RA, together with fibrinogen and CRP were higher in patients with infarcts of greater than 3 cm and lowest in patients with lacunar syndromes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778856 TI - Encephalopathy with parkinsonian features in children following bone marrow transplantations and high-dose amphotericin B. AB - Encephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high-dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high-dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non-central nervous system Epstein-Barr virus-lymphoproliferative disease and had autopsy-confirmed leukoenephalopathy. PMID- 7778857 TI - Cephalosporin-induced recurrent aseptic meningitis. AB - A 66-year-old woman had several episodes of aseptic meningitis associated with exposure to cephalexin, cefazolin, and ceftazidime. The cerebrospinal fluid IgG index was elevated, specific IgG-ceftazidime binding was shown, and skin allergy testing with cefazolin provoked a recurrence of meningitis. We postulate an acute hypersensitivity reaction involving an antigen-specific humoral immune response. PMID- 7778858 TI - Studies of the coding region of the neuronal glutamate transporter gene in amyotrophic lateral sclerosis. AB - Studies of the coding region of the neuronal glutamate transporter of 6 amyotrophic lateral sclerosis (ALS) patients and 10 controls show an identical pattern of four reported amino acid variations. No mutations and polymorphisms were detected in 5 sporadic ALS patients and a single patient with the familial form of the disease. PMID- 7778859 TI - Amarcord. PMID- 7778861 TI - Extracellular metabolism of pulmonary surfactant: the role of a new serine protease. PMID- 7778860 TI - Regulation of pulmonary vascular tone in the perinatal period. PMID- 7778862 TI - Chemical regulation of pulmonary airway tone. AB - Over the past three years, substantial progress has been made in dissecting out the role of each of these individual effector systems, namely, the leukotrienes, neuropeptides, and nitrogen oxides. The next major challenge is to understand how they function in an integrated fashion. PMID- 7778864 TI - Thermal adaptation in biological membranes: is homeoviscous adaptation the explanation? PMID- 7778863 TI - Endothelium as an endocrine organ. PMID- 7778865 TI - Regulation of glucose fluxes during exercise in the postabsorptive state. AB - The increase in glucose utilization by the working muscle would lead to hypoglycemia were it not accompanied by an increase in hepatic glucose production. Although the increase in glucose uptake is normally driven by mechanisms that are primarily independent of the action of insulin and other hormones, the response of the liver appears to be closely controlled by the endocrine system. Although considerable progress has been made in understanding the bases for the increases in glucose utilization and production, the means by which these two processes are coordinated to form the exercise response are unclear (e.g. feedback or central feedforward control). Work intensity affects the mechanisms by which glucose fluxes are regulated. For example, during moderate-intensity exercise, the glucoregulatory response resembles glucoregulation in the basal state in that under both conditions, glucose release from the liver is controlled by glucagon and insulin, and blood glucose levels are tightly controlled. The response to high-intensity exercise, on the other hand, takes on characteristics of the stress response, as described by Cannon (13). That is, the catecholamine response increases disproportionately for a given increment in work intensity, and glucose levels are no longer closely regulated, but increase. The specific factors that turn exercise into stress at higher work intensities are not well defined. Determining factors involved in the regulation of glucose fluxes are limited in some respects because the body is more sensitive than are experimental detection methods to various stimuli (glucose, hormones, neurotransmitter release). More complete delineation of mechanisms involved in the regulation of glucose fluxes will require the development of improved techniques and unique experimental models. The trend in the physiological sciences is for more study at the level of the gene. Technical limitations will be overcome or circumvented as knowledge of gene regulation and the development of genetically engineered animal models provide new avenues with which to address basic questions regarding the control of glucose fluxes during exercise. PMID- 7778866 TI - Inhibin, activin and the female reproductive axis. PMID- 7778867 TI - The role of reactive oxygen metabolites in glomerular disease. PMID- 7778868 TI - Progression of renal disease and renal hypertrophy. PMID- 7778869 TI - Transforming growth factor-beta and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis? AB - Both angiotensin II and TGF-beta are key mediators of glomerular and tubulointerstitial injury and fibrosis in progressive kidney diseases. It was thought that angiotensin II damages the kidney by increasing glomerular filtration pressure, whereas autocrine TGF-beta overexpression occurs from unidentified mechanisms. Recent studies reveal that angiotensin II is a potent inducer of TGF-beta synthesis in a variety of cells and that this mechanism exerts important biological effects including extracellular matrix accumulation, cell proliferation, and hypertrophy. Because these studies were performed in vitro, there is clear evidence that the biological effects were observed independently of the vasoconstrictive properties of angiotensin II. Although it is difficult to study angiotensin II-mediated effects in vivo without influencing systemic and glomerular blood pressure, further studies are needed to evaluate the ability of ACE-inhibitors and angiotensin II receptor blockers to suppress TGF-beta overexpression in selected models of chronic progressive kidney disease. PMID- 7778870 TI - Role of platelet-derived growth factor in renal injury. AB - Evidence indicates that PDGF is a major cytokine that impacts on the biology of renal cells and the pathogenesis of renal disease. The biologic effects of PDGF on cells and tissue, whether contraction, proliferation, matrix expansion, or cell migration, can result in beneficial or injurious consequences depending on the particular setting. Although expression of PDGF and PDGF receptors is required for glomerular development, their overexpression can be detrimental in renal disease. The chemotactic and mitogenic effects of PDGF are beneficial in recruitment and repopulation by mesangial cells in focal or diffuse necrotizing diseases. On the other hand, a sustained proliferative response can be detrimental to renal function. There is much to understand about PDGF's role in the cytokine network during renal development and renal injury. Understanding the mechanism of action of PDGF and, specifically, the signaling molecules transduced by the PDGF receptor may lead to the development of new therapeutic strategies to offset the detrimental effect of PDGF. Methods of targeting PDGF to hypocellular or necrotic areas to effect tissue remodeling and repair are a desirable goal (28). On the other hand, promotion of fibroblast proliferation and smooth muscle cell proliferation is a detrimental effect of PDGF that contributes to interstitial and perhaps periglomerular fibrosis as well as atherosclerosis. Ultimately, understanding the role of PDGF and other cytokines in renal development and organogenesis will provide the means to treat glomerular pathology without residual scarring. PMID- 7778871 TI - Physiologic mechanisms of postischemic tissue injury. PMID- 7778872 TI - Molecular pathology of the skeletal muscle sodium channel. PMID- 7778873 TI - The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. PMID- 7778874 TI - Proteins and temperature. PMID- 7778875 TI - Mechanisms of activation of glutamate receptors and the time course of excitatory synaptic currents. PMID- 7778876 TI - Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. PMID- 7778877 TI - In defense of the oral cavity: structure, biosynthesis, and function of salivary mucins. PMID- 7778878 TI - The hydrophobic barrier properties of gastrointestinal mucus. AB - Impressive evidence has accumulated over the past 12 years indicating that one of the potentially important biophysical characteristics of mucus relates to its hydrophobic character. This surface property is region specific and reaches high values in the stomach and colon, where barrier properties against noxious agents in the lumen are most important. The hydrophobic properties of mucus appear to be related to its lipidic constituents and specifically to the presence of phospholipid surfactants that are synthesized, stored, and secreted by GI mucus cells in a regulated fashion. PMID- 7778879 TI - Signal transduction, packaging and secretion of mucins. PMID- 7778880 TI - Epithelial mucin genes. AB - The last seven years have been exciting in the world of mucin biology. Molecular analyses of mucin genes and deduced protein structures have provided insight into structural features of mucins and tools with which to examine expression, secretion, and glycosylation, thereby enabling a better understanding of the role of mucins in normal physiological processes and in disease. Functional studies are in progress both in vitro using cDNAs and cell lines and in vivo utilizing mutant mice in which a particular mucin gene has been inactivated or overexpressed. These studies should help determine whether the functions of mucins are restricted to protection and lubrication, or if they are involved in the adhesion of tumor cells to other cells or tissue components or in modulation of the immune system. PMID- 7778881 TI - Mucin biophysics. PMID- 7778882 TI - The evolution of endothermy in mammals and birds: from physiology to fossils. PMID- 7778883 TI - Cell biology of atherosclerosis. AB - The process of atherosclerosis is a life-threatening disease that affects critical organs including the heart and brain. It results from the influence of noxious agents associated with hyperlipidemia, hypertension, diabetes, cigarette smoking, homocysteinemia, and other agents that may, in altering the homeostatic condition of the artery wall, injure the endothelium and smooth muscle. The result is a protective, inflammatory, fibroproliferative response that becomes excessive and in its excess results in the disease process we call atherosclerosis. PMID- 7778884 TI - Angiotensin-converting enzyme inhibition and ventricular remodeling after myocardial infarction. PMID- 7778885 TI - Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. PMID- 7778886 TI - Leukocyte traffic in the lung. PMID- 7778887 TI - Collaborative development of middle-range nursing theories: toward a theory of unpleasant symptoms. AB - One promising approach to strengthening theory-research and theory-practice linkages is to place greater emphasis on developing and using theories of the middle range to underpin nursing research and practice. In this article, a postpositivistic definition of middle-range theory is advanced, an argument is made for shifting nursing's theory development activities from discipline defining grand theories to middle-range theories, and a collaborative and incremental approach to middle-range theory development is described and illustrated. A sustained substantive example is provided by the beginning development of a theory of unpleasant symptoms. PMID- 7778888 TI - Evolution of a grounded theory: conflict resolution through culture brokering. AB - This article describes the evolution of the middle-range substantive theory of culture brokering. The theory was generated by first conducting a concept analysis that yielded 12 attributes of the concept of culture brokering. The concept analysis was accomplished using the anthropology, health-related, and business literature. In addition, data from an interpretive ethnographic study were used to further develop the concept of culture brokering. The theory was then generated from four grounded theory studies. Each study was used to frame the grounded theory model and to strengthen and refine the categories and links between categories within the basic social process of culture brokering. The culture brokering theory can guide the practice of nurses in situations where conflict is present in the health care interaction. The theory is grounded in the experiences of nurses attempting conflict resolution in the context of health care interactions. PMID- 7778889 TI - Exploring the theoretical basis of nursing using advanced techniques of concept analysis. AB - In this article, the traditional methods of concept development are critiqued, and alternative methods that use qualitative methods of inquiry are presented. Variations of concept development techniques appropriate to the maturity of the concept being explored are then described, including methods for concept delineation, concept comparison, concept clarification, concept correction, and concept identification. To illustrate the application of concept development methods to nursing theory, a research program to delineate the construct of comfort is described. PMID- 7778890 TI - Casuistry, care, compassion, and ethics data analysis. AB - Traditional approaches to descriptive ethics data analysis do not explicate the nature of ethical dilemmas in critical care and emergency nursing. Using sensitizing concepts of causes of nurse compassion, 168 stories of ethical dilemmas were categorized. They were analyzed from the theoretical perspective of an ethic of care using casuistry. Paradigm cases for each sensitizing concept were constructed. The nature of ethical dilemmas is in the disparity between actual and ideal nursing practice. PMID- 7778892 TI - A treatise on nursing knowledge development for the 21st century: beyond postmodernism. AB - This article explicates a framework for nursing knowledge development that incorporates both modernist and postmodernist philosophies. The framework derives from an "open philosophy" of science, which links science, philosophy, and practice in development of nursing knowledge. A neomodernist perspective is proposed that upholds modernist values for unified conceptualizations of nursing reality while recognizing the dynamic and value-laden nature of all levels of theory and metatheory. It is proposed that scientific inquiry extend beyond the postmodern critique to identify nursing metanarratives of nursing philosophy and nursing practice that serve as external correctives in the critique process. Philosophic positions related to the science, philosophy, and practice domains are put forth for continued dialogue about future directions for knowledge development in nursing. PMID- 7778891 TI - Consciousness raising in participatory research: method and methodology for emancipatory nursing inquiry. AB - Nursing practice and research that are grounded in emancipatory inquiry challenge the inequalities and injustices that affect health in this society. Increasing numbers of nurse scholars have explored the use of emancipatory inquiries (particularly feminist theory and critical theory) as philosophic bases for nursing practice and as theoretical or methodologic perspectives for nursing research. This article presents participatory research as a methodology and consciousness raising as a method for nursing research that addresses the emancipatory goals of feminist and critical theories. An example of consciousness raising in a participatory nursing research project is offered. It is argued that participatory research can produce a revolutionary emancipatory knowledge for the future of nursing and health care. PMID- 7778894 TI - Expression of the pCloDF13 encoded bacteriocin release protein or its stable signal peptide causes early effects on protein biosynthesis and Mg2+ transport. AB - The effect of the pCloDF13 encoded bacteriocin release protein (BRP) on Escherichia coli cell lethality was studied. Induction of the BRP resulted in a strong inhibition of the incorporation of radioactive labeled amino acids and affected the transport of Mg2+ ions. Similar effects were obtained when the BRP stable signal peptide was expressed as a separate entity. Kinetic studies revealed that these effects occurred prior to quasi-lysis and release of cloacin DF13. The results indicated that the BRP induced cell lethality is caused by early effects on protein synthesis and Mg2+ transport, due to the accumulation of stable BRP signal peptides in the cytoplasmic membrane. PMID- 7778893 TI - Effects of growth conditions on mitochondrial morphology in Saccharomyces cerevisiae. AB - Effects of growth conditions on mitochondrial morphology were studied in living Saccharomyces cerevisiae cells by vital staining with the fluorescent dye dimethyl-aminostyryl-methylpyridinium iodine (DASPMI), fluorescence microscopy, and confocal-scanning laser microscopy. Cells from respiratory, ethanol-grown batch cultures contained a large number of small mitochondria. Conversely, cells from glucose-grown batch cultures, in which metabolism was respiro-fermentative, contained small numbers of large, branched mitochondria. These changes did not significantly affect the fraction of the cellular volume occupied by the mitochondria. Similar differences in mitochondrial morphology were observed in glucose-limited chemostat cultures. In aerobic chemostat cultures, glucose metabolism was strictly respiratory and cells contained a large number of small mitochondria. Anaerobic, fermentative chemostat cultivation resulted in the large, branched mitochondrial structures also seen in glucose-grown batch cultures. Upon aeration of a previously anaerobic chemostat culture, the maximum respiratory capacity increased from 10 to 70 mumole.min-1.g dry weight-1 within 10 h. This transition resulted in drastic changes of mitochondrial number, morphology and, consequently, mitochondrial surface area. These changes continued for several hours after the respiratory capacity had reached its maximum. Cyanide insensitive oxygen consumption contributed ca. 50% of the total respiratory capacity in anaerobic cultures, but was virtually absent in aerobic cultures. The response of aerobic cultures to oxygen deprivation was qualitatively the reverse of the response of anaerobic cultures to aeration. The results indicate that mitochondrial morphology in S. cerevisiae is closely linked to the metabolic activity of this yeast: conditions that result in repression of respiratory enzymes generally lead to the mitochondrial morphology observed in anaerobically grown, fermenting cells. PMID- 7778896 TI - Kinetics of conversion of Neisseria gonorrhoeae to resistance to complement by cytidine 5'-monophospho-N-acetyl neuraminic acid. AB - Freshly isolated gonococci upon subculture are readily lysed by normal human serum although a few strains remain inherently resistant to the complement activity. The sensitive gonococci can be converted to serum resistance by incubation with a host derived factor referred to as cytidine 5'-monophospho-N acetylneuraminic acid (CMP-NANA). These gonococci resist complement mediated killing due to their sialylation of an epitope structure on a component of lipo oligosaccharide (LOS). In the present study, the kinetics of conversion to serum resistance by the action of sialyltransferase (STase) in Neisseria gonorrhoeae was followed with very low concentrations of CMP-NANA. This conversion could not be perceived at 2 x 10(-3) nmol.ml-1 but was fully attainable from 8 x 10(-3) to 2 x 10(-2) nmol.ml-1 CMP-NANA. When pretreated up to 100 min in presence of the very low concentration of 2 x 10(-3) nmol.ml-1, a potentiating effect on the conversion of gonococci by 2 x 10(-2) nmol.ml-1 was observed in relation to the time of preincubation. This action was abolished after exposure to a subinhibitory concentration of chloramphenicol (0.5 microgram.ml-1). The gonococci recovered their ability to convert to serum resistance following adequate washing. The potential for increase in STase activity should be of interest for understanding the conversion from a serum sensitive to a serum resistance state. PMID- 7778895 TI - Physiological and technological aspects of large-scale heterologous-protein production with yeasts. AB - Commercial production of heterologous proteins by yeasts has gained considerable interest. Expression systems have been developed for Saccharomyces cerevisiae and a number of other yeasts. Generally, much attention is paid to the molecular aspects of heterologous-gene expression. The success of this approach is indicated by the high expression levels that have been obtained in shake-flask cultures. For large-scale production however, possibilities and restrictions related to host-strain physiology and fermentation technology also have to be considered. In this review, these physiological and technological aspects have been evaluated with the aid of numerical simulations. Factors that affect the choice of a carbon substrate for large-scale production involve price, purity and solubility. Since oxygen demand and heat production (which are closely linked) limit the attainable growth rate in large-scale processes, the biomass yield on oxygen is also a key parameter. Large-scale processes impose restrictions on the expression system. Many promoter systems that work well in small-scale systems cannot be implemented in industrial environments. Furthermore, large-scale fed batch fermentations involve a substantial number of generations. Therefore, even low expression-cassette instability has a profound effect on the overall productivity of the system. Multicopy-integration systems may provide highly stable expression systems for industrial processes. Large-scale fed-batch processes are typically performed at a low growth rate. Therefore, effects of a low growth rate on the physiology and product formation rates of yeasts are of key importance. Due to the low growth rates in the industrial process, a substantial part of the substrate carbon is expended to meet maintenance-energy requirements. Factors that reduce maintenance-energy requirements will therefore have a positive effect on product yield. The relationship between specific growth rate and specific product formation rate (kg product.[kg biomass]-1.h-1) is the main factor influencing production levels in large-scale production processes. Expression systems characterized by a high specific rate of product formation at low specific growth rates are highly favourable for large-scale heterologous protein production. PMID- 7778899 TI - Children, chronic illness, and surgery--an inoperable combination without caring perioperative nurse champions. PMID- 7778900 TI - AORN urges members to share expertise with Congressional representatives. PMID- 7778898 TI - The diversity of Malassezia yeasts confirmed by rRNA sequence and nuclear DNA comparisons. AB - One hundred and four Malassezia strains (52 isolated from humans and 52 from animals) were compared using large subunit (LSU) ribosomal RNA sequence similarity and nuclear DNA complementarity. Eight groups of strains were recognized as genetically distinct species. Each taxon was confirmed by a homogeneous mole % GC and percentages of DNA/DNA reassociations higher than 85%. The non-lipid-dependent Malassezia yeasts were maintained as the unique taxon M. pachydermatis. In contrast, lipid-dependent strains were shown to be distributed among seven species: M. furfur, M. sympodialis and M. species 1-5. These taxa matched remarkably well with morphological and serological differences documented by previous investigators. The LSU rRNA sequences allowed a further intraspecific resolution with most of genomic taxa represented by several closely related sequences: M. pachydermatis counted up to seven sequences, M. furfur four sequences, M. species 1 comprised three sequences and M. species 2 and M. species 5 two sequences. Three species, M. sympodialis, M. species 3 and M. species 4, displayed a unique type of sequence. Thus, the present report demonstrates the usefulness of sequencing for both taxonomic and epidemiological purposes. PMID- 7778897 TI - Secretion of an antibacterial factor during resuscitation of dormant cells in Micrococcus luteus cultures held in an extended stationary phase. AB - A high proportion of Micrococcus luteus cells in cultures starved for 3-6 months in spent medium following growth to stationary phase in batch culture lost the ability to grow and form colonies on agar plates, but could be resuscitated from dormancy by incubation in liquid medium containing supernatant taken from the late log phase of viable cultures of the same organism (Kaprelyants et al. 1994). In the present work, we found that during the first 50-70 h of such resuscitation the dormant cells actually divide for 10-17 generations in lactate minimal medium containing yeast extract whilst remaining nonculturable on agar plates. Further incubation results in a decrease in the total cell number in liquid medium. The addition of viable (culturable) Micrococcus luteus cells in concentrations of up to 10(4) ml-1 to test tubes containing either resuscitating cells or supernatant from these cultures revealed the excretion of a factor or factors which inhibited the proliferation of otherwise viable cells. The maximum production of this factor took place after some 96 h of incubation of starved cells in resuscitation medium. Supernatant from late logarithmic phase batch cultures of M. luteus abolished the antibacterial effect of starved cultures incubated in resuscitation medium. It is concluded that the stimulating effect of viable cells, and of supernatant taken from batch cultures, on the resuscitation of dormant cells might be connected in part with overcoming the activity of an antibacterial factor causing self-poisoning of dormant cells during their resuscitation. PMID- 7778901 TI - AORN recommended education standards for RN first assistant programs. PMID- 7778902 TI - Laparoscopic Nissen fundoplication to treat gastroesophageal reflux. AB - Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux. The procedure involves wrapping the gastric fundus around the lower end of the esophagus to augment the lower esophageal sphincter. The procedure offers several advantages over open laparotomy, including smaller abdominal incisions, reduced postoperative discomfort, and shortened postoperative recovery and hospital stays. The laparoscopic approach also reduces the length of time a patient has an ileus. PMID- 7778903 TI - Congenital idiopathic clubfoot deformities. AB - Clubfoot is a birth defect that is marked primarily by a deformed talus (ie, ankle) and calcaneous (ie, heel) that give the foot a characteristic "club-like" appearance. In congenital idiopathic clubfoot (ie, talipes equinovarus), the infant's foot points downward (ie, equinus) and turns inward (ie, varus), while the forefoot curls toward the heel (ie, adduction). This congenital disorder has an incidence of 1 in 400 live births, with boys affected twice as often as girls. Unilateral clubfoot is somewhat more common than bilateral clubfoot and may occur as an isolated defect or in association with other disorders (eg, chromosomal aberrations, cerebral palsy, spina bifida, arthrogryposis). Infantile clubfoot deformity is painless and is correctable with early diagnosis and prompt treatment. PMID- 7778904 TI - Selective dorsal rhizotomy to decrease spasticity in cerebral palsy. AB - Until recently, treatment of muscle spasticity in children with cerebral palsy has consisted of physical therapy, bracing, and surgery to release and lengthen tight tendons of contracted muscles and correct muscle contractures. Selective dorsal rhizotomy is a surgical intervention that selectively cuts the spinal sensory nerve rootlets carrying the most abnormal signals, thereby reducing spasticity in all muscle groups of the affected extremities. It is not a cure for spastic cerebral palsy. Children who have this procedure can gain significant increases in knee and thigh ranges of motion and increased strength and muscle control if they have good family support and follow through with intensive postoperative physical therapy. PMID- 7778905 TI - Implementing a parent-present induction program. AB - One of the greatest fears of children undergoing surgery is separation from their parents. Children for whom preoperative sedation is contraindicated often endure the distress of this separation and the beginning of anesthesia surrounded by masked strangers. Those who receive sedation often experience the invasiveness of a medication administered rectally or intramuscularly or the insertion of an IV line. Until recently, the doors to the operating room remained closed to family members. Like other hospitals throughout the country, however, Children's Hospital in Boston has responded to the concerns of parents and staff members by implementing a parent-present anesthesia induction program. As a result, the surgical experience for many children and families has changed significantly for the better. PMID- 7778906 TI - Laser ablation of recurrent laryngeal papillomas in children. AB - Papillomas are the most common laryngeal tumors in childhood, and their etiology is thought to be viral. Papillomatosis (ie, widespread, multiple papillomas) may involve a child's airway from the epiglottis to the bronchi. Hoarseness is an early sign of juvenile laryngeal papillomas (JLP), and airway obstruction is a later, life-threatening sign. The recurrence and spread of JLP is common. An otorhinolaryngologist may perform a tracheostomy on a child with JLP; however, this procedure is avoided if possible, because a tracheostomy predisposes the trachea to papilloma seeding. Laser ablation of papillomas through the use of rigid endoscopic equipment and a carbon dioxide laser is the mainstay of therapy. PMID- 7778907 TI - Development of a perioperative nursing diagnoses flow sheet. AB - Traditionally, health care professionals in the preoperative, intraoperative, and postoperative phases of care have used perioperative records that focus on the technical aspects of the care provided (eg, blood pressure, pulse measurements; equipment used) and leave room for only short narratives to document nursing care. Such formats often do not document the multitude of activities or interventions perioperative nurses provide. The question raised at the DePaul Health Center, St Louis, was: "Where do we document our nursing diagnoses and plan of care?" The response was to create a nursing diagnosis task force that investigated the feasibility of a form professional nurses could use in all phases of patient care. This investigation led to the development, implementation, and universal use of a perioperative nursing diagnoses flow sheet within the surgical services department. PMID- 7778908 TI - Implementation of a regional pediatric trauma center. AB - Today's hospitals face unique challenges in the treatment of pediatric trauma patients. With the advent of more sophisticated regional trauma systems, there is a growing awareness that children are not "little adults," but are a special component of the trauma patient population. As few communities can provide pediatric health care facilities committed to trauma care, regional pediatric trauma centers need to be developed and implemented so hospitals can provide pediatric trauma patients with comprehensive and age-appropriate care. This article describes the steps taken by the Children's Hospital Medical Center, Cincinnati, to develop a regional pediatric trauma center according to the guidelines set forth by the American College of Surgeons committee on trauma. PMID- 7778910 TI - Physicians are my coworkers, not my clients. PMID- 7778909 TI - Hepatic artery chemoembolization therapy for hepatic tumors. AB - Patients with hepatocellular carcinomas who undergo chemoembolization therapies require skilled perioperative nursing care that addresses their knowledge deficits about chemoembolization techniques, their anxieties related to chemoembolization procedures and adverse effects, and their impaired mobility resulting from the presence of arterial lines and the progression of the cancer. Perioperative nursing participation in chemoembolization procedures is an example of the expanded role of today's OR nurse. PMID- 7778912 TI - Alcohol abuse and nurses. PMID- 7778911 TI - Debate about "any willing provider" laws continues in 1995. PMID- 7778913 TI - Proposed recommended practices for selection and use of packaging systems. PMID- 7778914 TI - Proposed recommended practices for documentation of patient care in the perioperative practice setting. PMID- 7778915 TI - Addition of rifampin to conventional therapy for recurrent furunculosis. PMID- 7778916 TI - Bart's syndrome. Ultrastructure and genetic linkage. AB - BACKGROUND AND DESIGN: Bart's syndrome, originally described in a large family in 1966, consists of congenital localized absence of skin, blistering, and associated nail abnormalities. Since then, several descriptions of patients with similar clinical findings have suggested that this syndrome may represent any of the three subtypes of epidermolysis bullosa: epidermal, junctional, or dermal. Because no histologic or ultrastructural studies were done in Bart's kindred, and neither immunohistologic nor genetic linkage technology was available at that time, classification of the syndrome has been unclear. We report the findings of clinical, ultrastructural, immunohistologic, and genetic linkage studies of the original kindred and their descendants. We contacted original family members and their descendants by telephone and questionnaire. Skin biopsy specimens adjacent to blisters were obtained for ultrastructural and immunochemical analysis. Blood samples were drawn from affected members and their spouses and children for genetic linkage studies. RESULTS: The clinical findings seen in the descendants of the original family with Bart's syndrome were similar to those described in 1966. We did, however, detect persistence of blistering into adult life and mild atrophic scarring and milia formation at sites of blistering in some family members, a finding not noted in the original study. Hypertrophic scarring and albopapuloid lesions were not detected. Ultrastructural analysis of skin from affected family members showed poorly formed anchoring fibrils and cleavage below the lamina densa. Immunohistochemical staining localized type IV collagen at the roof of blistered skin. Staining for type VII collagen was found to have a normal distribution in nonblistered skin. Genetic linkage studies mapped the gene for the disease in this family to chromosome 3p at or near the site of the gene encoding type VII collagen. CONCLUSION: Bart's syndrome is a subtype of dominantly inherited dystrophic epidermolysis bullosa. PMID- 7778917 TI - Characteristics of toxic epidermal necrolysis in patients undergoing long-term glucocorticoid therapy. AB - BACKGROUND AND DESIGN: The usefulness of steroid therapy in toxic epidermal necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur in patients who undergo long-term steroid therapy. We, thus, looked for the potential effect of long-term glucocorticosteroid therapy before the onset of TEN on altering the progression of the disease. The records of 179 patients were reviewed. The characteristics of the 13 patients who were undergoing long-term glucocorticosteroid therapy were compared with those of 166 other patients with TEN. The following parameters were studied: age, mortality, delay between the introduction of the suspect drug and the onset of TEN, length of hospital stay, body surface area involved, time elapsed between the first symptom of TEN and hospital admission, number of medications taken by the patients before the onset of TEN, lymphocyte count, granulocyte count, platelet count, glycemia, serum aspartate aminotransferase level, and total disease duration. RESULTS: Patients who were undergoing long-term glucocorticosteroid therapy differed from other patients with TEN in the administration of more drugs, longer delay between the introduction of the suspect drug and the onset of TEN, and a longer time elapsed between the first symptom of TEN and hospital admission. We observed no differences for the other parameters that were studied. CONCLUSION: Our study shows that long-term steroid therapy may delay the onset of TEN, but it does not halt its progression. PMID- 7778918 TI - Lymphoproliferative responses to Borrelia burgdorferi in patients with erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis benigna cutis, and morphea. AB - BACKGROUND AND DESIGN: Specific humoral and cell-mediated immune responses play an important role in the pathogenesis of Lyme borreliosis. Several previous studies demonstrated that a specific cellular immune response to Borrelia burgdorferi can occur independently of a diagnostic humoral response. Little is known about T-cell reactivities against B burgdorferi in early and late cutaneous manifestations of Lyme borreliosis. We studied the lymphoproliferative response of peripheral blood mononuclear cells to B burgdorferi antigen from 99 patients (25 with erythema migrans, 16 with acrodermatitis chronica atrophicans, 13 with lymphadenosis benigna cutis, and 45 with localized scleroderma) and 21 control subjects. The results are expressed as a stimulation index (SI) (mean count per minute of triplicate cultures with stimulant divided by mean count per minute without stimulant). The serum samples from all patients and control subjects were tested for antibodies to B burgdorferi by indirect immunofluorescence assay. RESULTS: The 21 healthy seronegative controls had an SI of 3.3 +/- 2.0 (mean +/- SD). Compared with that of control subjects, the SIs were significantly elevated in patients with erythema migrans (9.8 +/- 9.1), acrodermatitis chronica atrophicans (11.8 +/- 8.2), and lymphadenosis benigna cutis (7.2 +/- 6.2). The 45 patients with localized scleroderma had elevated proliferative responses, with an SI of 6.5 +/- 7.3, but these responses did not significantly differ from those of controls. Elevated titers of antibodies to B burgdorferi were present in six (24%) of 25 patients with erythema migrans, five (38%) of 13 patients with lymphadenosis benigna cutis, and 13 (29%) of 45 patients with localized scleroderma. All 16 patients with acrodermatitis chronica atrophicans had markedly elevated antibody titers. CONCLUSIONS: Our findings show that a significant lymphoproliferative response to B burgdorferi occurs in the majority of patients with cutaneous manifestations of Lyme borreliosis. The lymphocyte proliferation assay may be of diagnostic value in patients in whom Lyme borreliosis is strongly clinically suspected and who have nondiagnostic levels of antibodies against B burgdorferi. PMID- 7778919 TI - No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment. AB - BACKGROUND AND DESIGN: Early treatment of erythema migrans is important to prevent late complications. Minocycline possesses several attributes, making it potentially useful in the treatment of borrelial infections. In our study, minocycline was administered to 14 patients with erythema migrans. Punch biopsy specimens were obtained from the (affected) skin of all patients before and after therapy. The formalin-fixed, paraffin-embedded specimens were analyzed by polymerase chain reaction for the presence of Borrelia burgdorferi-specific DNA. RESULTS: Polymerase chain reaction assay succeeded in amplifying B burgdorferi specific DNA from the first biopsy specimen, obtained from the border of erythema migrans before initiating treatment, in eight (57%) of 14 patients. At the end of minocycline therapy, however, polymerase chain reaction analysis disclosed no B burgdorferi-specific DNA in any of the 14 patients. The good clinical response of our patients with erythema migrans substantiates our molecular findings. CONCLUSIONS: The presented polymerase chain reaction data, together with the clinical outcome, indicate that minocycline may be useful for treatment of early Lyme borreliosis. PMID- 7778920 TI - Transforming growth factor alpha gene expression in cultured human keratinocytes is unaffected by cellular aging. AB - BACKGROUND: Cultured human keratinocyte grafts have been shown to stimulate endogenous reepithelialization of both chronic nonhealing and acute partial thickness wounds. This effect is most likely mediated by cytokines that stimulate keratinocyte growth, such as transforming growth factor alpha. The effect of cellular age on cytokine expression by cultured grafts used for this purpose is presently undefined. In this study, transforming growth factor alpha gene expression in cultured foreskin keratinocytes from donors varying in age from 2 to 82 years was analyzed semiquantitatively by two separate methods, ie, Northern hybridization and competitive polymerase chain reaction. RESULTS: No pattern of decline in transforming growth factor alpha messenger RNA expression with increasing cellular age was observed by either analysis. CONCLUSION: The results indicate that expression of transforming growth factor alpha by cultured grafts may not be significantly affected by increasing cellular age and suggest that, even in the elderly, cultured autografts may be effective as pharmacologic agents for wound treatment. PMID- 7778922 TI - Dynamic epidermal cooling during pulsed laser treatment of port-wine stain. A new methodology with preliminary clinical evaluation. AB - BACKGROUND AND DESIGN: The clinical objective in the treatment of a patient with port-wine stain (PWS) undergoing laser therapy is to maximize thermal damage to the PWS, while at the same time minimizing nonspecific injury to the normal overlying epidermis. With dynamic cooling, the epidermis can be cooled selectively. When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the cooling remains localized in the epidermis, while leaving the temperature of the deeper PWS vessels unchanged. RESULTS: Comparative measurements obtained by a fast infrared imaging detector demonstrated that the surface temperature prior to laser exposure could be reduced by as much as 40 degrees C using the dynamic cooling technique. No skin surface textural changes were noted on PWS test sites cooled with a 20- to 80-millisecond cryogen spurt after flashlamp-pumped pulsed dye laser (FLPPDL) exposure (lambda = 585 nm; tau p = 450 microseconds) at the maximum light dosage possible (10 J/cm2). In contrast, epidermal necrosis occurred on the uncooled sites after such exposure. Six months after laser exposure, clinically significant blanching on the cooled sites indicates laser photothermolysis of PWS blood vessels did occur. CONCLUSIONS: Our preliminary experiments demonstrate the feasibility of selectively cooling the normal overlying epidermis without affecting the temperature of the deeper PWS vessels. Furthermore, protection of the epidermis from thermal injury, produced by melanin light absorption at clinically relevant wavelengths, can be achieved effectively. An additional advantage of dynamic epidermal cooling is reduction of patient discomfort associated with FLPPDL therapy. Further studies are under way to determine an optimum strategy for applying this dynamic cooling technique during pulsed laser treatment of patients with PWS and others with selected dermatoses (dermal melanocytic lesions and tattoos). PMID- 7778921 TI - Full-thickness skin grafts. Clinical observations on the impact of using epinephrine in local anesthesia of the donor site. AB - BACKGROUND AND DESIGN: A recent animal study indicated that epinephrine in local anesthesia adversely affects the survival of full-thickness skin grafts. Because animal models do not always correlate to humans, we performed a prospective observational study to elucidate the clinical outcome of using epinephrine in local anesthesia of the donor site. Seventy-two patients had cutaneous tumors excised by the Mohs micrographic technique. The resultant surgical defects were repaired using full-thickness skin grafts. Patients were randomly divided into two groups based on the local anesthetic used at the donor site: (1) 1% lidocaine (Xylocaine) (n = 33) or (2) 1% lidocaine with 1:100,000 epinephrine (n = 39). RESULTS: Assessment of the skin grafts at 1 week revealed a significantly increased risk of developing graft complications in the lidocaine with epinephrine group compared with the plain lidocaine group. The overall cosmetic outcome of the grafted site at 6 weeks revealed no significant difference between the two groups. CONCLUSIONS: Because there was only a minimal clinical effect of epinephrine on graft survival observed at 1 week and there was no effect on the 6 week cosmetic outcome, we do not recommend harvesting all full-thickness skin grafts with plain lidocaine. In certain clinical circumstances with compromised vascular supply or poor oxygenation, the use of plain lidocaine may be advantageous. PMID- 7778923 TI - Human papillomavirus and widespread cutaneous carcinoma after PUVA photochemotherapy. AB - BACKGROUND: Oral psoralen with UV-A (PUVA) photochemotherapy is known to cause cutaneous malignancies and has been associated with cutaneous immunosuppression. Human papillomavirus infection has also been associated with cutaneous malignancies and with immunosuppressed individuals. We therefore sought evidence of human papillomavirus infection in a patient with a long history of PUVA therapy and multiple cutaneous malignancies. OBSERVATIONS: During a 15-year period, an otherwise healthy patient with psoriasis who had undergone a 10-year course of PUVA photochemotherapy developed 13 squamous cell carcinomas, eight lesions diagnosed as "squamous cell carcinoma vs keratoacanthoma," 14 other keratoacanthomas, six basal cell carcinomas, one melanoma in situ, and 18 other keratinocytic dysplasias. Twenty-two of the 30 lesions tested for human papillomavirus DNA by polymerase chain reaction were positive for type 16/18, including six of the seven basal or squamous cell carcinomas tested. CONCLUSION: We hypothesize that PUVA therapy-induced immunosuppression may play an important role in PUVA-related carcinogenesis by affecting the extent and pathogenicity of human papillomavirus infection. PMID- 7778924 TI - Leukocytoclastic vasculitis following staphylococcal protein A column immunoadsorption therapy. Two cases and a review of the literature. AB - BACKGROUND: Protein A immunoadsorption is a novel therapy for the treatment of diseases mediated by pathogenic autoantibodies. This procedure consists of circulating patients' plasma through a column containing staphylococcal protein A, which binds to the Fc portion of IgG, enabling removal of IgG. Presently, protein A immunoadsorption is used in the treatment of idiopathic thrombocytopenic purpura, but may be more widely used as an immunomodulator in human immunodeficiency virus infection and metastatic carcinoma. OBSERVATIONS: We present two histologically documented cases of leukocytoclastic vasculitis in the setting of protein A immunoadsorption. This potentially severe adverse effect is probably more common than the literature reflects and should be recognized by physicians who are treating patients with protein A column pheresis. CONCLUSIONS: The pathogenesis of protein A therapy-associated leukocytoclastic vasculitis remains unclear. Further study of vasculitis in the setting of protein A column pheresis may lead to modifications of this therapy, resulting in fewer adverse effects. Protein A-associated leukocytoclastic vasculitis may serve as a useful model of the relation of immune complexes and vasculitis. PMID- 7778926 TI - A young adult with a recalcitrant scalp folliculitis. Langerhans' cell histiocytosis (LCDH) presenting as scalp folliculitis in an adult. PMID- 7778925 TI - Fibroblastic rheumatism. AB - BACKGROUND: Fibroblastic rheumatism was first described in the French literature in 1980. Since that time, 11 other patients with this disorder have been identified in the literature, mostly from France. This is a unique syndrome characterized by the sudden onset of symmetric polyarthritis and cutaneous nodules ranging from 5 to 20 mm in diameter, with predilection for the upper and lower extremities. While the cutaneous findings resolve spontaneously after several months, permanent joint sequelae are common. OBSERVATIONS: We present the first two patients with fibroblastic rheumatism reported in the United States. The clinical features and histologic findings were identical to those of patients described in the European literature. CONCLUSIONS: Fibroblastic rheumatism is a relatively rare syndrome characterized by the association of multiple cutaneous nodules with polyarthritis. The clustering of cases in France may, in part, be attributable to increased recognition by clinicians owing to prevalence of reports in the European literature. Perhaps, as clinicians in the United States become familiar with this disorder, further cases will be diagnosed, and the pathogenesis of the disorder will be elucidated. PMID- 7778927 TI - Scalp mass. Giant molluscum contagiosum. PMID- 7778928 TI - Chronic alopecia. Trichotillomania. PMID- 7778929 TI - Enlarging scalp nodule. Proliferating trichilemmal cyst (PTC). PMID- 7778930 TI - Erythema multiforme. Should anyone care about the standards of care? PMID- 7778932 TI - Flashless office macro photography. PMID- 7778931 TI - Cutaneous heterotopic meningeal nodules. PMID- 7778933 TI - Combined features of pemphigus foliaceus and bullous pemphigoid: immunoblot and immunoelectron microscopic studies. PMID- 7778934 TI - Cutaneous malignancies in patients treated with psoralen photochemotherapy (PUVA) for vitiligo. PMID- 7778935 TI - Treatment of lentigo maligna with the carbon dioxide laser. PMID- 7778936 TI - Photodynamic therapy of nonmelanoma skin cancer with topical aminolevulinic acid: a clinical and histologic study. PMID- 7778937 TI - Olmsted syndrome in twins. PMID- 7778938 TI - Sezary's syndrome and human immunodeficiency virus infection. PMID- 7778939 TI - Traditional treatment of Buruli ulcer in Benin. PMID- 7778940 TI - Allergic reaction to intralesional triamcinolone acetonide: a case report. PMID- 7778941 TI - Herpetic whitlow in an infant without defined risks. PMID- 7778942 TI - Acute generalized livedo reticularis with myasthenialike syndrome revealing parvovirus B19 primary infection. PMID- 7778943 TI - [Cysticercosis in Madagascar: consensus research. Research group on cysticercosis]. PMID- 7778945 TI - [Workshop on cysticercosis. Antananarivo, 4 December 1993. Proceedings and abstracts]. PMID- 7778944 TI - [Relations between pathology and immunity in cysticercosis]. AB - Human Taenia solium cysticercosis is identified as a main Public Health problem in many developing countries, such as Mexico, India or Madagascar. In this paper are presented the complex relationships between the anatomical position of the cysts, the associated pathology and the immune reactions observed in the laboratory. Detecting specific antibodies, or circulating antigens in a near future, in serum or cerebrospinal fluid is not enough for a reliable diagnosis. A crucial aspect remains concentrated on the use of computed tomography in a first step. PMID- 7778946 TI - [Value of immunodiagnosis by ELISA and Western blotting for the diagnostic and therapeutic management of neurocysticercosis]. AB - The humoral immune response in neurocysticercosis was studied in seventy patients from the Reunion Island (Indian Ocean). In the serum and the cerebrospinal fluid, specific antibodies were quantified using an enzyme-linked (ELISA) and Western blot (EITB) technique. It was found that two antigenic fractions, of 13 and 14kd molecular weight, are highly specific of an active disease, for which the treatment is recommended. This new result, established in the quite simple epidemiologic environment of the Reunion island, is under validation in Madagascar. PMID- 7778948 TI - [History of a hepatic lesion: Schistosoma mansoni bilharziasis]. AB - Schistosomiasis mansoni is a widespread tropical disease affecting about 200 million people in the world (data from the World Health Organization). The adult worms, settled in the mesenteric venous plexus, can survive in the host during 5 to 20 years. They evade the immune response and are not, by themselves, the main cause of the pathological events. Most eggs are swept into the portal circulation and trapped in different systemic organs, including the liver. The continuous egg deposition results in a T cell-mediated granulomatous response that is responsible for the disease syndrome (chronic hepatitis associated with a dense fibrosis and a concurrent portal hypertension). Current immunological and molecular concepts on the modulation of the granuloma, and the associated fibrosis, lead to a better understanding of the pathogenesis of human schistosomiasis. Chemotherapy with praziquantel is presently the main approach of morbidity control, before using in conjunction a human vaccine still in development. PMID- 7778947 TI - [Clinical immunology of hepato-splenic bilharziasis]. AB - Field studies on immunity in human schistosomiasis gave evidence for a slow development with age of an acquired resistance to reinfection. Recent results support the idea of a progressive build-up of high levels of protective IgE, and probably IgA, overcoming the initial influence of blocking Ig G4 antibodies. Chemotherapy does not apparently modify the susceptibility to infection. A. Capron's candidate vaccine is now ready for human trials, and represents a promising tool in controlling schistosomiasis morbidity while diminishing the parasite transmission efficiency. PMID- 7778949 TI - [Why compare hepatosplenic bilharziasis in six African countries with the help of ultrasonography? Presentation of a WHO project including Madagascar]. AB - During a morbidity survey in two endemic foci of hepatosplenic schistosomiasis in the malagasy Hauts Plateaux (Tetikanana, 80 km East of Ambositra and Lohanosy, in the vicinity of Antananarivo), the objectives of a comparative pathology WHO project are presented. The survey in Madagascar was concurrently organized by the Ministry of Health (Bilharziasis central laboratory, DLMT), the Parasitology Unit of the local Pasteur Institute and the Medical Parasitology Institute of Bonn University, in Germany. This was the fourth part of this investigation of the morbidity variation due to Schistosoma mansoni infection in six african countries, a project sponsored by the WHO within its TDR programme. This comparison was based on the standardized description of morbidity as visualized by echography, following the "Cairo-1990" and the "Hannover-Managil-1989" classifications, and on coprology. One of the main objectives of this study was to demonstrate a morbidity variation at the scale of the African region (due to different S. mansoni strains or to a variable genetic background within the studied human populations), while participating to an international standardization effort for field echography. The project was conducted since July 1991 by a constant medical staff from Bonn and Hannover german universities. Eight foci in four african countries (Senegal, Mali, Uganda and Madagascar) are still analyzed and we are presenting here the first results. The data of an independent ultrasonographic investigation, organized by the Blair Institute and the Danish Bilharziasis Laboratory in Zimbabwe, was kindly proposed for this comparison. This project will end with the study of two supplementary foci in Tanzania and Burundi. PMID- 7778950 TI - [Schistosomiasis mansoni infection in a hyperendemic region of midwestern Madagascar: epidemiology, morbidity and secondary effects of praziquantel treatment]. AB - The examination of 544 inhabitants (93.2% of the whole population) of a village in the middle west of Madagascar, where Schistosoma mansoni is hyperendemic and where no previous antischistosomal treatment had been delivered at a community level, showed a prevalence rate of 61.8%. The highest prevalences and the most intense infections were observed in the 10-24 age group. The egg count decreases dramatically from the age of 25. A highly significant relationship was found between recent histories of bloody diarrhoea and S. mansoni eggs excretion. Clinical examination showed a high frequency of splenomegalies (62.2% > or = stade 2 Hackett), with two modes: one in the 10-14 age group and the other in the 35-39 age group. The respective liability of S. mansoni and malaria remain to be clarified. Side effects after treatment of the entire population with praziquantel were observed in 27.2% of treated individuals. Side effects occurred mainly in infected people. A highly significant relationship was found between intensity of infection and frequency of these side effects which are essentially mild and disappear in the 24 hours. PMID- 7778951 TI - [Evolution of Schistosoma mansoni bilharziasis in Ampefy (Lake Itasy) from 1986 to 1993]. AB - In 1976, 1983, 1986 to 1989 and 1993, the population of Ampefy, on the shores of lake Itasy, was invited to participate in an active detection programme of Schistosoma mansoni infection. An increase in the global prevalence was observed from 1976 (17.0%) to 1983 (40.0%). This prevalence level was then stabilized during the four years annual selective treatment (1986 to 1989) and the mean intensity of infection for positive patients fell from 393 eggs/g to 271 eggs/g and the proportion of severe infections, with a high risk of developing "hepatosplenic disease", fell from 8% to 4.2%. Selective treatment was interrupted from 1989 to 1993, during which time the global prevalence rose to 70.6% and mean intensity of infection to 594 eggs/g, with 22% of those examined classified as severely infested. This local control programme, associating active detection with annual treatment, seems effective in stabilizing prevalence and intensity of infection in spite of a regular arrival of infested, and never treated, immigrants. However, its impact throughout time is limited. PMID- 7778952 TI - [Experimental study of a Malagasy strain of Schistosoma haematobium: compatibility with different Bulinus snails, potential intermediate hosts]. AB - Experimental investigation on a malagasy strain of S. haematobium: compatibility with different Bulinus snails, potential intermediate hosts. A comparative experimental study of the infectivity of different Bulinus snails by a reference S. haematobium strain was made under laboratory conditions. The results support the role of Bulinus obtusispira as an intermediate host in Madagascar but some other Bulinus species could exist and play a role in the fields far away from the experimental criteria here described. PMID- 7778953 TI - [ Reflections on the national program for bilharziasis control in Madagascar]. PMID- 7778954 TI - 'You promised me I wouldn't die like this!' A bad death as a medical emergency. PMID- 7778955 TI - What do apple pie and motherhood have to do with feeding tubes and caring for the patient? PMID- 7778956 TI - Treating the dying patient. The challenge for medical education. PMID- 7778957 TI - Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia. AB - BACKGROUND: Switch therapy is defined as the early transition from intravenous to oral antibiotics during treatment of infection. This study was designed to evaluate the clinical outcome and length of stay of hospitalized patients with community-acquired pneumonia treated with an early switch from intravenous to oral third-generation cephalosporins. METHODS: Patients with a new roentgenographic pulmonary infiltrate and at least two symptoms (cough, fever, or leukocytosis) were enrolled in this study and treated with intravenous ceftizoxime sodium (1 g every 12 hours) or ceftriaxone sodium (1 g every 24 hours). Patients were switched to oral cefixime (400 mg every 24 hours) as soon as they met the following criteria: (1) resolution of fever; (2) improvement of cough and respiratory distress; (3) improvement of leukocytosis; and (4) presence of normal gastrointestinal tract absorption. RESULTS: Of the 120 patients enrolled, 75 (62%) had clinical data evaluated. Long-term follow-up showed that 74 patients (99%) were cured; one patient required readmission for further intravenous therapy. Mean duration of hospital stay was 4 days. CONCLUSIONS: This investigation demonstrated that an early switch to oral cefixime may be reasonable in hospitalized patients with community-acquired pneumonia who have already shown a good clinical and laboratory response to therapy with intravenous third-generation cephalosporins. This approach is clinically effective and minimizes hospital stay. PMID- 7778958 TI - Cardiopulmonary resuscitation in intensive care unit and non-intensive care unit patients. Immediate and long-term survival. AB - OBJECTIVE: To determine the effect of location within the hospital and preexisting electrocardiographic rhythm on the outcome of cardiopulmonary resuscitation, the cardiopulmonary resuscitation records for a 3-year period, including 668 hospitalized patients, were retrospectively reviewed. RESULTS: Resuscitation was successful in only 12 patients in the intensive care unit (3.3%) and 43 patients not in the intensive care unit (14.0%), 20 of whom were on a telemetry unit. Patients who survived to discharge had similar 1-year survival rates regardless of initial hospital location, although intensive care unit patients had the best 3-year survival rate, and there were no survivors at 3 years in the group that received cardiopulmonary resuscitation in the nonmonitored hospital bed. Survival was best with an initial cardiac rhythm of ventricular tachycardia or fibrillation, but all non-ventricular tachyarrhythmias were associated with survival. Age was not an apparent factor, while survival to hospital discharge favored whites over blacks. CONCLUSIONS: Futile resuscitative efforts are routinely performed in part because physicians and patients are unaware of outcome results and factors that influence survival. A wider recognition of the limitations of cardiopulmonary resuscitation should lead to advanced directives that reflect this awareness, with substantially more patients choosing not to have cardiopulmonary resuscitation. PMID- 7778959 TI - National trends in the concurrence of tuberculosis and acquired immunodeficiency syndrome. AB - BACKGROUND: Elucidation of the relationship between tuberculosis (TB) and the acquired immunodeficiency syndrome (AIDS) is needed to help predict the future course of these two epidemics. We examined nationwide trends in TB and AIDS occurring in the same individual. METHODS: Health departments in the 50 states, District of Columbia, Puerto Rico, and Guam matched their TB and AIDS case registries to determine the number of persons diagnosed with both TB and AIDS. The number of AIDS cases, TB cases, AIDS cases that matched with a TB case on the TB registry, and TB cases that matched with an AIDS case on the AIDS registry were reported to the Centers for Disease Control and Prevention, Atlanta, Ga. Data were analyzed for the period from 1981 through 1991. The number of matched TB-AIDS cases was compared with a modeled estimate of excess TB cases during the period from 1985 through 1990. RESULTS: From 1981 through 1991 there were 11,299 AIDS cases that matched with a TB case on the TB registry, representing 5.1% (geographic variation, 0% to 9.3%) of AIDS cases. The TB cases that matched with an AIDS case on the AIDS registry represent 4.3% (geographic variation, 0% to 15.1%) of TB cases from 1981 through 1991. Since 1981, matched TB and AIDS cases increased yearly through 1990. When examined by year of AIDS report, the percentage of AIDS cases that matched with a TB case increased from 1981 to 1982 (1.9% to 5.1%), remained fairly constant from 1983 through 1987 (range, 4.0% to 4.7%), increased in 1988 (5.4%) after extrapulmonary TB was added to the AIDS case definition, and increased slightly through 1990 (5.8%). When examined by year of TB report, the percentage of TB cases that matched with an AIDS case increased steadily from 1981 through 1990 (0.1% to 9.5%). The calculated fraction of excess TB cases during the period from 1985 through 1990 that could be accounted for by identified TB-AIDS cases was 30%. CONCLUSION: The risk of TB or AIDS among persons already diagnosed with one disease is much higher than among the general population. The percentage of persons with TB who are also diagnosed with AIDS has been increasing rapidly. Human immunodeficiency virus-induced immunosuppression is an important contributor to the TB epidemic and probably accounts for a minimum of 30% of excess TB cases during the period from 1985 through 1990. PMID- 7778960 TI - Physicians as patients. Choices regarding their own resuscitation. AB - BACKGROUND: Attitudes toward cardiopulmonary resuscitation have changed considerably during the last 30 years. Although physicians are routinely involved in the decision making about cardiopulmonary resuscitation for their patients, little is known about their collective preferences regarding it for themselves. METHODS: A questionnaire was distributed at an internal medicine primary care review course at an urban community hospital. Of the 111 physicians registered at the meeting, 72 (65%) completed the questionnaire and serve as the basis for the results. Physicians were asked if they would want cardiopulmonary resuscitation for themselves in the presence of an acute myocardial infarction, Alzheimer's disease, and nine other advanced chronic diseases at the projected ages of 40, 60, and 80 years. RESULTS: At all projected ages, physicians' desire for cardiopulmonary resuscitation with any advanced chronic disease was significantly less than with an acute myocardial infarction (P < or = .000001 except for rheumatoid arthritis). Fewer physicians wanted cardiopulmonary resuscitation at age 80 years than at 40 years for any disease (P < or = .002). The results did not differ when analyzed by respondents' age, gender, or primary care specialty, or the size of the community in which they practiced. CONCLUSIONS: The results of this initial survey indicate that most physicians would not want cardiopulmonary resuscitation with a variety of underlying chronic diseases and corresponding functional impairments--particularly with advancing age. Conversely, with an acute myocardial infarction, all physicians surveyed would desire cardiopulmonary resuscitation at age 40 years, and many would continue to desire it with advancing age. PMID- 7778961 TI - Nocturnal dyspnea and atrial fibrillation predict Cheyne-Stokes respirations in patients with congestive heart failure. AB - BACKGROUND: Cheyne-Stokes respirations have frequently been noted in highly selected groups of patients with congestive heart failure, but their prevalence in an unselected population with congestive heart failure is undefined. METHODS: One hundred consecutive unselected outpatients or stable inpatients with clinical congestive heart failure encountered by three clinical cardiologists during a 6 month period were screened for Cheyne-Stokes respirations with overnight oximetry. RESULTS: The mean age (+/- SD) of the patients was 70 +/- 8.6 years. Of the 100 patients, 33% had had previous coronary bypass surgery, 77% were men, 57% had hypertension, and 32% had atrial fibrillation. The mean ejection fraction (+/ SD) was 34% +/- 13%. Periodic breathing was assessed qualitatively as Cheyne Stokes respirations in 27% of patients, nonspecific sleep-disordered breathing (apneas and/or hypopneas) in 43%, and normal in 30%. For patients with Cheyne Stokes respirations, patients with nonspecific sleep-disordered breathing, and normal subjects, the mean numbers of oxyhemoglobin desaturation events per hour were 24, 10, and 2, and the total numbers of desaturations of 4% or more that lasted less than 3 minutes were 172, 74, and 13. Independent predictors of Cheyne Stokes respirations vs non-Cheyne-Stokes respirations included a history of nocturnal dyspnea (odds ratio, 4.00; 95% confidence interval, 1.33 to 12.04; P = .01) and atrial fibrillation (odds ratio, 3.24; 95% confidence interval, 1.21 to 8.48; P = .02). CONCLUSIONS: Cheyne-Stokes respirations and nonspecific sleep disordered breathing are common in unselected patients with congestive heart failure, and Cheyne-Stokes respirations are predicted by a history of nocturnal dyspnea and the presence of atrial fibrillation. Techniques designed to modify the nocturnal breathing pattern of patients with congestive heart failure may be applicable to a large portion of the congestive heart failure population. PMID- 7778962 TI - Temporal trends of incident human immunodeficiency virus infection in a cohort of injecting drug users in Baltimore, Md. AB - OBJECTIVE: To measure the temporal trends in the incidence of infection with human immunodeficiency virus in a cohort of injecting drug users in Baltimore, Md, between 1988 and 1992. DESIGN: Study subjects were screened for antibodies to human immunodeficiency virus by enzyme-linked immunosorbent assay and confirmed with Western blot. They were followed up at 6-month intervals with repeated serologic screening and comprehensive interviews for human immunodeficiency virus risk factors. SETTING: Special study clinic. PARTICIPANTS: A cohort of 2960 participants were recruited and screened between February 1988 and March 1989. Recruitment criteria included an age of 18 years or older, a history of illicit drug injection since 1978, and the absence of the acquired immunodeficiency syndrome; subjects were subsequently tested for human immunodeficiency virus antibodies. Most subjects (85%) were not receiving methadone treatment at baseline and were recruited by word of mouth. MAIN OUTCOME MEASURE: Human immunodeficiency virus seroconversion. RESULTS: Of the 2247 seronegative participants at baseline, 1532 were followed up, and 188 (12.3%) had seroconverted by December 1992. The incidence of human immunodeficiency virus infection over time among users declined somewhat, especially among women; the overall incidence was 1.90 per 100 person-semesters, or 3.80% annually. The incidence, adjusted for gender, was higher in younger (< 35 years) than older (> or = 35 years) subjects (relative incidence, 1.75; 95% confidence interval, 1.29 to 2.38) and in women compared with men, adjusted for age (relative incidence, 1.29; 95% confidence interval, 0.95 to 1.80). The relative incidence among active compared with inactive drug users adjusted for age and gender was 1.58 (95% confidence interval, 1.06 to 2.35). CONCLUSIONS: Although the incidence of human immunodeficiency virus infection in this cohort of injecting drug users in Baltimore declined somewhat during the 4 years of follow-up, especially among women, the persistent annual incidence of nearly 4% during 3 1/2 to 4 1/2 years of observation suggests the need for additional strategies for prevention of infection, especially among those who continue injecting drugs. Newer methods of prevention, such as provision of sterile injection equipment, an effective human immunodeficiency virus vaccine, and wider availability of effective treatment or prevention of drug addiction, are urgently needed in these high-risk populations. PMID- 7778963 TI - Impact of continued geriatric outpatient management on health outcomes of older veterans. AB - BACKGROUND: Although previous trials have proved inpatient-based geriatric assessment to be beneficial, to our knowledge, the effectiveness of outpatient geriatric assessment has not been established. We examined the effectiveness of an outpatient geriatric evaluation and management (GEM) clinic. METHODS: Hospitalized veterans aged 65 years or older with impairment of activities of daily living, chronic disease, polypharmacy, or two or more hospitalizations in the previous year were randomized to an outpatient GEM team clinic (n = 60) or usual care (n = 68). After an initial comprehensive assessment, they received long-term management in the geriatric clinic. Principal outcomes included health status (mortality, hospitalizations, health perception, and medications), function (activities of daily living, instrumental ADL, and social activity), affect (Center for Epidemiologic Studies-Depression test score and life satisfaction), and cognition (Mini-Mental State examination score). RESULTS: At randomization, no significant differences were noted between the groups. The average age of the patients was 71 years (range, 65 to 93 years). At 1 year following randomization, GEM clinic patients compared with subjects receiving usual care had significantly improved health perception, took fewer medications despite increased number of diagnoses, reported greater social activity, had improved Center for Epidemiologic Studies-Depression scale scores, and had higher life satisfaction scores. There was a trend toward improved performance of activities of daily living for GEM clinic patients. The GEM clinic patients had a 54% lower mortality (6.8% vs 14.9%). Overall, no differences were observed in the total number of hospitalizations between the groups. CONCLUSIONS: The combination of long-term management following comprehensive outpatient assessment significantly improved aspects of health status (including health perception and medications), function (including social activity), and affect (including depression and life satisfaction) for older veterans and may influence mortality and function. PMID- 7778964 TI - Determinants of black-white differences in the risk of cerebral infarction. The National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. AB - OBJECTIVE: To determine whether blacks in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study remained at increased risk for cerebral infarction after adjusting for stroke risk factors and sociodemographic factors. METHODS: A cohort study involving 8203 whites and 1362 blacks who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. During the 13-year follow-up, 538 and 122 cerebral infarctions occurred in whites and blacks, respectively. RESULTS: The black-white risk for cerebral infarction varied by age (P = .007 for race-age interaction). Compared with whites of the same age, blacks aged 35 to 44 years were at significantly increased risk for cerebral infarction (relative risk, 2.62; 95% confidence interval, 1.23 to 5.57), while older blacks, those older than 64 years, were not at increased risk (relative risk, 1.14; 95% confidence interval, 0.90 to 1.46). The relative risk for cerebral infarction decreased to 2.07 (95% confidence interval, 0.97 to 4.42) in younger blacks and 0.82 (95% confidence interval, 0.29 to 2.33) in older blacks after adjustment for age, sex, education, history of heart disease, diabetes, systolic blood pressure, treatment for hypertension, Quetelet index, and serum hemoglobin and magnesium levels. CONCLUSIONS: These results indicate that much of the increased risk for cerebral infarction experienced by blacks can be explained by their higher prevalence of stroke risk factors, especially diabetes, hypertension, and lower educational attainment. Younger blacks, however, may still be at increased risk after adjusting for stroke risk factors. PMID- 7778965 TI - Sweet taste (dysgeusia). The first symptom of hyponatremia in small cell carcinoma of the lung. AB - Three patients with small cell carcinoma of the lung presented with a persistent unpleasant sweet taste as their initial and only symptom. On further evaluation, they were found to have hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone. In each case, resolution of the sweet taste paralleled an increase in serum sodium concentration after water restriction alone. Linkage of the sweet taste with a low serum sodium concentration strongly implicates hyponatremia--rather than tumor, antidiuretic factor, medications, or chemotherapy--as the central mechanism responsible for this previously unreported (to our knowledge) sentinel symptom of small cell carcinoma of the lung. PMID- 7778966 TI - Calculating gains in life expectancy with risk factor reduction. PMID- 7778967 TI - Clinical laboratory test findings in patients with chronic fatigue syndrome. PMID- 7778968 TI - [Myxoma of the left atrium as the cause of sudden death? An unusual fatality]. AB - Case report of a 67-year-old woman who was found under mysterious circumstances 3 weeks after she had died. Main result of the autopsy was a myxoma of considerable size in the left atrium. Epidemiology, pathology and clinical aspects are presented. The myxoma's possible meaning as cause of death is examined in a fatality where the inquiry was restricted because of the corpse being putrefied and partly eaten away by maggots. PMID- 7778969 TI - [Suicide in the Geneva canton (1971-1990). An analysis of the forensic medicine autopsy sample]. AB - During the twenty-year period from 1971 to 1990, 1654 cases of suicide were examined at the Institute of Forensic Medicine of Geneva University. The suicide rate for the entire population averaged 22,75 per 100,000 population per annum. The male to female ratio was 1.5:1. The average age was 47. The highest suicide rate lay between ages 27 and 32 for men and between ages 45 and 50 for women. The most common means of suicide chosen by men were the use of firearms (28%) and hanging (21%) whilst women preferentially chose falling from a height (26%), poisoning (24%) or drowning (22%). Carbon monoxide poisoning, the major means of suicide before 1971 (20%), has greatly decreased whereas firearms, formerly representing only 13% of all suicides before 1971, have become the principal means (19%). May, January and September have, respectively, the highest rate of suicide. PMID- 7778971 TI - [Recoil-induced rifle butt mark on the ceiling in suicidal gunshot injury]. AB - In a suicide case the butt of the weapon (double-barrelled shotgun) produced a characteristically shaped mark at the ceiling, which could be physically explained by the recoil effect and was a clue that the victim had fired the shot himself. The ammunition used was a cartridge with a rifled shotgun slug (Brenneke type). The contact shot into the temple resulted in the rupture of the skull with exenteration of the brain. As the weapon remained lying on the body of the suicide after the shot, brownish traces of rust could form at the places of contact with steel parts. PMID- 7778970 TI - [6 cases of premeditated murder of adults by drowning]. AB - Premeditated murder of adults by drowning is rare and hard to investigate. Six cases are reported. If the aim of the killer is homicide by drowning to begin with (primary drowning), it is usually difficult to prove as morphological findings are missing of may be insignificant and ambiguous. If, on the other hand, the killer opts for drowning only as a conclusion to a primarily differently planned assault (e.g. strangling), the finding patterns are different, and their interpretation is usually easier (secondary drowning). PMID- 7778972 TI - [Fatal gunshot wound injuries with so-called shooting ball-point pens]. AB - Report on two suicides using shooting ball-point pens (with .22 lr and .22 lr Hv cartridges respectively). Both cases were contact shots (in the first case in the area of the right ear, in the second case in the left temple). Corresponding to the configuration of the barrel end, the muzzle imprints were uncharacteristic (ring-shaped and narrow). The other morphological findings of the wounds did not differ from the injuries inflicted by conventional small-bore weapons. PMID- 7778973 TI - Isolation and characterisation of a strain of Pseudomonas putida that can express a periplasmic nitrate reductase. AB - A strain of Pseudomonas putida that can express a nitrate reductase that is located in the periplasmic compartment was isolated from freshwater. The enzyme was active in vivo during arginine fermentation and at the onset of oxygen limitation in batch cultures. The activity of the enzyme increased the yield of bacteria following fermentative growth under anoxic conditions with arginine, but nitrate reduction did not support growth on non-fermentable carbon substrates under anoxic conditions. Cells expressing the periplasmic nitrate reductase were capable of reducing nitrate in the presence of oxygen. Nitrate reduction under oxic conditions was clearly coupled to a respiratory electron transport chain because: (1) the process was sensitive to the respiratory inhibitors rote-none and 2-n-heptyl-4-hydroxyquinoline N-oxide, and (2) membrane-bound and periplasmic cytochromes were involved. This is the first report of the presence of a periplasmic nitrate reductase in a member of the gamma proteobacteria. PMID- 7778974 TI - Evidence of two pathways for the metabolism of phenol by Aspergillus fumigatus. AB - Aspergillus fumigatus (ATCC 28282), a thermotolerant fungus, has been shown to be capable of growth on phenol as the sole carbon and energy source. During growth of the organism on phenol, catechol and hydroquinone accumulated transiently in the medium; cells grown on phenol oxidised these compounds without a lag period. Two different routes operating simultaneously, leading to different ring-fission substrates, are proposed for the metabolism of phenol. In one route, phenol undergoes ortho-hydroxylation to give catechol, which is then cleaved by an intradiol mechanism leading to 3-oxoadipate. In the other route, phenol is hydroxylated in the para-position to produce hydroquinone, which is then converted into 1,2,4-trihydroxybenzene for ring fission by ortho-cleavage to give maleylacetate. Cell-free extracts of phenol-grown mycelia were found to contain enzymic activities for the proposed steps. Two ring-fission dioxygenases, one active towards 1,2,4-trihydroxybenzene, but not catechol, and one active towards both ring-fission substrates, were separated by FPLC. Succinate-grown mycelia did not oxidise any of the intermediates until a clear lag period had elapsed and did not contain any of the enzymic activities for phenol metabolism. PMID- 7778975 TI - Metabolic pathways and energetics of the acetone-oxidizing, sulfate-reducing bacterium, Desulfobacterium cetonicum. AB - Acetone degradation by cell suspensions of Desulfobacterium cetonicum was CO2 dependent, indicating initiation by a carboxylation reaction. Degradation of butyrate was not CO2-dependent, and acetate accumulated at a ratio of 1 mol acetate per mol butyrate degraded. In cultures grown on acetone, no CoA transfer apparently occurred, and no acetate accumulated in the medium. No CoA-ligase activities were detected in cell-free crude extracts. This suggested that the carboxylation of acetone to acetoacetate, and its activation to acetoacetyl-CoA may occur without the formation of free acetoacetate. Acetoacetyl-CoA was thiolytically cleaved to two acetyl-CoA, which were oxidized to CO2 via the acetyl-CoA/carbon monoxide dehydrogenase pathway. The measured intracellular acyl CoA ester concentrations allowed the calculation of the free energy changes involved in the conversion of acetone to acetyl-CoA. At in vivo concentrations of reactants and products, the initial steps (carboxylation and activation) must be energy-driven, either by direct coupling to ATP, or coupling to transmembrane gradients. The delta G' of acetone conversion to two acetyl-CoA at the expense of the energetic equivalent of one ATP was calculated to lie very close to 0 kJ (mol acetone)-1. Assimilatory metabolism was by an incomplete citric acid cycle, lacking an activity oxidatively decarboxylating 2-oxoglutarate. The low specific activities of this cycle suggested its probable function in anabolic metabolism. Succinate and glyoxylate were formed from isocitrate by isocitrate lyase. Glyoxylate thus formed was condensed with acetyl-CoA to form malate, functioning as an anaplerotic sequence. A glyoxylate cycle thus operates in this strictly anaerobic bacterium. Phosphoenolpyruvate (PEP) carboxykinase formed PEP from oxaloacetate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778976 TI - Molecular cloning and characterization of the extracellular sucrase gene (sacC) of Zymomonas mobilis. AB - The Zymomonas mobilis gene sacC that encodes the extracellular sucrase (protein B46) was cloned and expressed in Escherichia coli. The gene was found to be present downstream to the already described levansucrase gene sacB in the cloned chromosomal fragment of Z. mobilis. The expression product was different from SacB and exhibited sucrase but not levansucrase activity; therefore, SacC behaves like a true sucrase. Expression of sacC in E. coli JM109 and XL1 was very low; overexpression was observed in E. coli BL21 after induction of the T7 polymerase expression system with IPTG. Subcellular fractionation of the E. coli clone carrying plasmid pLSS2811 showed that more than 70% of the sucrase activity could be detected in the cytoplasmic fraction, suggesting that the enzyme was soluble and not secreted in E. coli. The nucleotide sequence analysis of sacC revealed an open reading frame 1239bp long coding for a 413 amino acid protein with a molecular mass of 46 kDa. The first 30 deduced amino acids from this ORF were identical with those from the N-terminal sequence of the extracellular sucrase (protein B46) purified from Z. mobilis ZM4. No leader peptide sequence could be identified in the sacC gene. The amino acid sequence of SacC showed very little similarity to those of other known sucrases, but was very similar to the levansucrases of Z. mobilis (61.5%), Erwinia amylovora (40.2%) and Bacillus subtilis (25.6%). PMID- 7778977 TI - Fatty acid profiles of "Pasteurella" piscicida: comparison with other fish pathogenic gram-negative bacteria. AB - The fatty acid methyl ester (FAME) profiles of "Pasteurella" piscicida were determined by gas chromatography and subjected to numerical analysis in comparison with those obtained for Vibrio anguillarum, Aeromonas salmonicida and Pasteurella species of clinical origin. The bacterial species studied shared important characteristics with respect to their FAME content: in all of them the saturated and unsaturated fatty acids of 16 carbon atoms were the predominant fatty acids. However, distinguishing features could be detected for each pathogen. Using either single linkage or complete linkage algorithms, strains were divided into four phena that corresponded to the different species, but showed a high degree of correlation among them. Although single linkage discriminated strains better within each phenum, complete linkage was more useful to establish the relationships among clusters. The results obtained support the idea that "Pasteurella" piscicida is related to members of the genera Vibrio and Aeromonas and indicate the need for exhaustive genetic studies to clarify the taxonomic position of this fish pathogen. PMID- 7778978 TI - Growth-phase-dependent alginate synthesis, activity of biosynthetic enzymes and transcription of alginate genes in Pseudomonas aeruginosa. AB - Alginate synthesis by the highly mucoid Pseudomonas aeruginosa 8821 M is growth phase-dependent, and the alginate produced per unit of biomass reaches maximum values in the deceleration phase of growth. However, the degree of polymerization increases as batch growth proceeds, reaching maximum values at the stationary phase of growth. The activity of the four enzymes leading to GDP-mannuronic acid formation, phosphomannose isomerase, phosphomannomutase, GDP-mannose pyrophosphorylase and GDP-mannose dehydrogenase peaked earlier at the late exponential phase. Growth-phase-dependent activity of alginate biosynthetic enzymes correlates with the level of transcription of the encoding alginate genes algA, algC and algD during growth, as indicated by Northern blot hybridization experiments. The pattern of coordinate transcriptional growth-phase regulation of these alginate structural genes concurs with the growth-dependent transcription of the regulatory gene algR1. PMID- 7778979 TI - [The effect of a different protein and fiber intake on the ileal flow of endogenous protein in 15N-labeled swine]. AB - The endogenous N in ileal digesta of pigs was estimated in two experimental variants. In variant 1 the crud protein content of a wheat-maize-fish meal diet was 18% and the crude fibre content was 1.9% (diet 1) and 2.7% resp. (diet 2). In variant 2 the crude protein content was 12.5% (wheat-maize-diet) and the crude fibre content was 4.1% (diet 3) and 5.5% resp. (diet 4). The higher crude fibre content of the diets 2-4 was provided by means of a supplementation with partially hydroyzed straw meal plus pectin (2:1 w/w). Four miniature pigs with an average initial body weight of 29 kg, were fitted with a ileocaecal re-entrant cannula and received each one of the four different diets. 15NH4Cl, added to the diets, was given for 5 days (150 mg 15N-excess/kg0.75 BW*d) to label the animals with 15N. Ileal digesta, urine and faeces were collected over 24 hours on 8th, 10th and 12th day after the first intake of 15N. The 15N-excess of urine N was used as the comparative measure of 15N-excess of endogenous protein. The amount of nitrogen collected in ileal digesta was in order of the diets 1-4 = 258, 299, 200 and 224 mg/kg0.75 BW*d and of these amounts were 50.1, 52.1, 56.1 and 50.4% of endogenous origin. This were corresponding, after conversion into crude protein to 9.1, 11.2, 10.8 and 11.0 g/100 g crude protein intake or 16.9, 19.7, 13.8 and 13.4 g/kg dry matter intake, respectively. The bacterial N-flow were in order the diets 1-4 = 94.0; 72.7; 55.8 and 52.6 mg/kg0.75 BW*d and 73, 46, 50 and 47% resp. of the endogenous N or 36, 24, 28 and 24% of the ileal total N. The results show, that the absolute amounts of endogenous and bacterial N at the terminal ileum were significantly increased by a higher crude protein content of the diet. The percentage of endogenous and bacterial N on the total N of the ileal digesta was not affected neither by the crude protein content of the diets nor by the fibre supplements. PMID- 7778980 TI - [The effect of avilamycin and tylosin on the apparent digestibility of iron, zinc, copper, manganese and selenium in the beginning and ending performance of swine]. AB - In two metabolism trials with growing and finishing pigs the effect of the antibiotic feed additives Avilamycin and Tylosin on the apparent digestibility of Fe, Zn, Cu, Mn and Se was investigated. The feed additives were supplied to the diet in levels of 40 ppm (growing pigs) and 20 ppm (finishing pigs) each. Dietary contents of Fe, Zn, Cu, Mn and Se covered the requirements of all treatment groups. Avilamycin and Tylosin increased the apparent digestibility by 4 (Fe), 4 (Zn), 5 (Cu), 2 (Mn) and 2 (Se) percentage units on an average. PMID- 7778981 TI - [Age and sex dependent variation in the content of Fe, Zn, Cu and Mn in different body parts and their retention in fattening pigs]. AB - The concentrations of Fe, Zn, Cu and Mn were determined in meat, inner organs, blood and residual carcass in a total of 24 barrows and gilts of 60 kg and 100 kg of live weight, respectively. the finisher diet contained 192 ppm Fe, 113 ppm Zn, 18 ppm Cu and 65 ppm Mn with, as calculated, a great proportion originating from the mineral supplement. During growth, the contents of Fe, Cu and Mn were significantly reduced. No sex differences occurred. In the lean meat of the 100 kg pigs, common values accounting for 1.1 mg Fe, 2.8 mg Zn and 0.05 mg Cu per 100 g were analyzed. The manganese concentration of 0.01 mg per 100 g, however, was considerably lower as the corresponding figure from nutrient tables. In the finishing period, the animals retained per animal and day about 18 mg Fe, 15 mg Zn and 0.2 mg Cu. Mn retention was not significantly different from zero. The low utilization rates calculated from these data can be partly explained by the moderately excessive supply in this fattening period. In order to reduce the trace element load of the soils, a considerably lower tolerance of excessive trace element contents in finisher diets has to be developed. PMID- 7778982 TI - Effect of raising dietary protein, amino acids and/or energy levels as an attempt to alleviate severity of the chronic aflatoxicosis by broiler chicks. 1. Performance and toxicity symptoms. AB - In an attempt to alleviate the aflatoxicosis symptoms by broiler chicks fed on low (50 ppb) aflatoxin-contaminated diet; the dietary nutrients were elevated by 2.6% for protein, 0.54 MJ ME/kg for energy or 0.5% for each of methionine and lysine. These supplements were mixed altogether and applied as well. All the experimental diets were offered for a 6-week period followed by a 2-week period on aflatoxin--free diet without supplements as a withdrawal period. It was proved after the treatment period that the raising of energy concentration was beneficial to overcome the aflatoxin effects on the body weight, feed conversion rate, and dressing (eviscerated weight) percentage and stability of relative weights of liver and kidneys. Additionally, the supplements' mixture improved the body weight and the relative weight of the liver comparing with the chicks fed on the aflatoxin diet without additives. All of the contaminated diets, except that of the high energy, caused apparently toxic symptoms besides the internal gross pathology. The high energy diet reflected the lowest mortality rate, whereas the highest was with the amino acids supplemented one. The withdrawal period resulted in lower differences among treatments in the body weight. It improved also the dressing percentage (significantly) and to some extent the results of the post mortem examination. PMID- 7778984 TI - The adherence of three Streptococcus bovis strains to cells of rumen epithelium primoculture under various conditions. AB - Three Streptococcus bovis strains were tested in biotype assay and examined for the adherence to cells of rumen epithelium primoculture. The adherence pattern of ruminal streptococci in phosphate buffered saline at pH values ranging from 4.1 to 8.5 was determined. Our isolates of Streptococcus bovis strains adhered best at pH 7.0-7.3. To characterize the adhesive determinants, the bacterial cells were exposed to various treatments. Protease treatment dramatically decreased the adherence of all Streptococcus bovis strains, thus suggesting that the determinants responsible for the adherence are largely proteinaceous. Carbohydrates could be also significantly involved in the active sites of bacterial surface because metaperiodate-treated cells adhered much more poorly than control, sodium iodate-treated cells. Addition of carbohydrates (lactose, maltose and saccharose) had no significant effect on the adherence of Streptococcus bovis strains although a slight decrease in the adhesion was detected. PMID- 7778983 TI - Effect of raising dietary protein, amino acids and/or energy levels as an attempt to alleviate severity of the chronic aflatoxicosis by broiler chicks. 2. Biochemical characteristics. AB - Aflatoxin caused some reduction in moisture contents of chest and liver, lipids of thigh and blood, blood glucose, muscular protein and GOT in liver. It led also to increase of moisture contents of thigh and kidneys; chest lipids; blood cholesterol; protein of liver, kidneys and blood and blood creatinine. The different supplements used herein led to increasing moisture of muscles, liver and kidneys (except on oil addition); lipids of muscles (except of chest on high energy diet) and blood (except on amino acids-supplemented diet); blood cholesterol (except on high energy one); protein of thigh (except on high protein one) and blood (except on high energy or amino acids diets) and liver GPT (except on high energy diet). The additives led also to low blood glucose; protein of chest (except on high energy), liver, and kidneys; blood creatinine; liver GOT (particularly with high energy or amino acids); plasma GOT (on high amino acids) and plasma GPT. The 2-week withdrawal period led to low moisture contents of muscles and kidneys of most treatments, although they continued higher than in the control for chest, liver and kidneys. It increased blood glucose and cholesterol with continuous higher lipid content of muscles and blood and blood cholesterol than in the control. It led to elevated protein content of muscles, liver (except on the control or supplements mixture), kidneys (on the aflatoxin alone or with the amino acids) and blood (except on the control or aflatoxin alone or with high protein) and blood creatinine (except on the control or on the high energy or the supplements mixture).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7778985 TI - [15N-flow after in sacco incubation and feeding of sheep and goats with untreated wheat straw or straw treated with 15N horse urine]. AB - Chopped wheat straw was homogeneously mixed with urine of horses (5.75 gN per 1, 16.88 atom-% 15N-excess) and airtightly stored in plastic containers for 6 months. Three rumen fistulated sheep and goats each were fed with untreated or urine treated straw. Concentrate was added to straw. Untreated and urine treated straw were given in nylon bags and incubated in the rumen of sheep and goats for 1, 3, 6, 12, 24, 48 and 72 hours. A three compartment exponential function was used to fit the measurements of 15N-excess and 15N-amount of bag content. The curves and the calculated partial Y-values of the three compartments show the inflow and outflow of 15N into or from the bags and allow conclusions about the binding of urine N. Most N of urine was not compactly bound by straw during storage. Primarily microbial N was attached to the straw in the rumen. About 6% of urine N were bound more compact to the straw. Similar curves were calculated for 15N-excess and 15N-amount of nylon bags. The curves allow conclusions about tracer flows without quantitative knowledge. There were no significant differences between animal species. PMID- 7778986 TI - [Delirium after open-heart surgery. Prevalence, risk factors and therapeutic approach]. PMID- 7778987 TI - [Infective endocarditis in children and adolescents]. AB - PURPOSE: To assess infective endocarditis (IE) predisposing factors, etiologic agents and hospital course in infants and adolescents. METHODS: We Studied 222 patients admitted under compatible IE diagnosis, from 1985 to 1990. The population of this study is fifty patients (23%) under 16 years of age. RESULTS: Rheumatic valvular disease, as predisposing cardiopathy was proeminent within 9 to 16 years of age, markedly Statistical difference when compared to age range of 0 to 8 years (p < 0.05). Among congenital cardiopathies, the most frequent were: interventricular septal defect (26.0%) and tetralogy of Fallot (21.7%). Blood cultures, surgical material or emboli cultures were positive in 35 (70.0%) assessed patients. Streptococcus viridans (45.7%) and Staphylococcus aureus (42.8%) were the etiologic agents most often isolated. It was found that endocarditis by Staphylococcus aureus had mortality rate of 53.3% [(clinical (66.6%) and surgical (44.4%)], (p < 0.05) when compared to those by Streptococcus viridans; with total mortality of 6.2% (no clinical death and 16.6% in the surgical group). Total in-hospital mortality (clinical and surgical) was 26.0% (13 deaths). CONCLUSION: IE in infants and adolescents in this studied population presented Streptococcus viridans responsible for 46.7% of patients with endocarditis and the Staphylococcus aureus for 42.8% were the etiologic agents most often found. Total, clinical and surgical mortality was greater in patients with endocarditis by Staphylococcus aureus when compared with those by Streptococcus viridans. Among the congenital cardiopathies, whether operated on or not, ventricular septal defect and of Fallot's tetralogy were the most involved ones; rheumatic cardiopathy Still remains a significant predisposing factor to infective IE in our country. PMID- 7778988 TI - [Comparative study of transthoracic Doppler echocardiogram, computed tomography and aortography in the diagnosis of thoracic aortic dissection]. AB - PURPOSE: Comparative and prospective evaluation of three methods (transthoracic echo-Doppler (TTE), computerized tomography (CT) and aortography (AORT) utilized for aortic dissection diagnosis. METHODS: The 39 patients with confirmed aortic dissection (surgery or autopsy) underwent, within a few hours of each other, all three methods scrutinized. There were 19 cases of type A and 20 of type B dissection. RESULTS: In type A dissection the methods were equivalent (TTE = 73.7%, CT = 84.2%, AORT = 73.7% p = NS) but for type B, TTE was significantly inferior to the other two methods (TTE = 60%, TC 90%, AORT = 80%, p < 0.05 for TTE, for TC and AORT p = NS). In three occasions, even though all three methods were performed, the diagnosis was not obtained. CONCLUSION: The methods which were evaluated make the diagnosis in the majority of cases. In type A all methods are similar, however, in type B, TC and AORT are superior to TTE. Even performing all three methods in each patient, in three instances the diagnosis was not made. PMID- 7778990 TI - [Radiofrequency catheter ablation of type I atrial flutter]. AB - PURPOSE: To verify the efficacy and safety of the creation of a barrier with radiofrequency (RF) in the tricuspid annulus and the vena cava ostium (TA-IVC). METHODS: Nine consecutive patients, 7 males, with age ranging from 36 to 76 years, with paroxysmal (7 patients) or permanent (2) type I atrial flutter (negative P wave in lead II, III and F) were submitted to RF ablation of TA-IVC istmo. One deflectable catheter with 4mm size tip was introduced into the right ventricle apex and pulled back to the inferior vena cava. When the atrial electrogram was detected the RF application was started. The RF was applied (20 watts during 60s) up to the proximity of inferior vena cava ostium. The end point was to stop atrial flutter. Then a vigorous atrial stimulation protocol, including isoproterenol infusion was used. In the next day, patients were submitted to transesophageal stimulation with the same protocol. RESULTS: Atrial flutter was interrupted in all patients (100%) with 4 to 28 (mean 16.7 +/- 7.7) applications. Eight patients (88.8%) with one session and 1 (11.1%) with two sessions. The mean time spent to stop the atrial flutter with one application was 30.5 +/- 18.5s. There were no complications. After a mean follow up of 3 +/- 1.6 month all patients (100%) are asymptomatic. Two of them are taking propranolol to control symptomatic atrial and ventricular ectopic beats. CONCLUSION: RF ablation of the TA-IVC istmo is efficient and safe in a short term follow up to interrupt and prevent re-induction and recurrence of type I atrial flutter. PMID- 7778989 TI - [Comparative study of the extension of coronary arteriosclerosis with risk factors and changes in the retinal artery]. AB - PURPOSE: To identify a possible relationship of the extent of coronary artery disease, with risk factors for coronary artery disease and the retinal arteriolar changes (evaluated by fundoscopic examination). METHODS: We studied 96 patients (66 males), 36 to 72 years of age. All patients were studied by selective cinecoronaryarteriography, fundoscopic examination, as well as evaluated for the common risk factors, cigarette smoking diabetes, dislipidemia, systemic hypertension, age, alcoholism, male sex, family history and obesity. RESULTS: Male (p < 0.001) and smoking (p < 0.01) were the statistically significant associations with the extent of coronary artery disease. No significant relationship with the extent of coronary artery disease was present for the other risk factor nor for changes in retinal arteriolar branches. CONCLUSION: A relationship between extent of coronary artery disease with male sex and a cigarette smoker is occurred. No relationship with other risk factors, nor with retinal arteriolar changes were present. PMID- 7778991 TI - [Evaluation of QRS voltage in 12 derivations and Cornell criteria in the diagnosis of left ventricular hypertrophy]. AB - PURPOSE: To search for the existence and degree of correlation between total 12 lead ECG amplitude and the sum of RaVL + SV3 > 28 mm (for men) or > 20mm (for women) and left ventricular hypertrophy (LV mass calculated by echocardiography > 215g for both sexes). METHODS: ECG and echocardiograms of 227 consecutive patients were examined and submitted to statistical analysis searching for correlation between total 12 lead ECG amplitude and Cornell criteria and LV mass (ASE formula modified by Devereux). RESULTS: Patients had ischemic heart disease, hypertension, valvular disease, cardiomyopathy or other less common heart diseases, or had no cardiac illness at all. There was statistically significant association of total 12 lead amplitude > 120mm and Cornell criteria with LV mass > 215g (p = 0.02 and p = 0.01 respectively). Total ECG amplitude showed 74.3% sensitivity, 42.6% specificity, and 52.4% accuracy. Cornell criteria showed values of 37.8%, 82.7% and 68.7% respectively. CONCLUSION: Total 12-lead amplitude presented limited diagnostic performance for detecting LV hypertrophy, as well as did ECG Cornell criteria, although the latter was more specific and more accurate. PMID- 7778992 TI - [Acquired ventricular septal defect during infective endocarditis]. AB - We studied five patients with acquired ventricular septal defect during the course of an infective endocarditis. All patients were male and had a previous aortic valve disease associated with an aortic ring abscess. Clinical examination was useful for the diagnosis of 4 cases, emphasizing the following findings: systolic murmur and/or left paraesternal thrill and right-heart failure. Incidence of congestive heart failure was 60%, while 40% of all patients died during the in-hospital course. No specific etiologic agent was detected. Therefore, acquired ventricular septal defect should be suspected in patients with infective endocarditis of the aortic valve that evolve with a systolic murmur and/or paraesternal thrill and right-heart failure. Immediate surgical treatment is mandatory in these cases. PMID- 7778993 TI - [Congenital cerebral arteriovenous fistula. Diagnostic peculiarity and surgical repair in an infant with heart failure]. AB - A case of 3 month-old-boy with Down's syndrome and heart failure due to a localized arteriovenous fistula of the cranial vessels is reported. Clinical diagnosis was made after cranial bruit detection based on a retroauricular thrill incidentally felt by the mother. The diagnosis was confirmed by digital subtraction angiography and a good result was achieved by means of embolization and surgical ligation of the fistula. Three years after the operation the patient is asymptomatic, on no medication and with normal magnetic resonance image of the cranial vessels. PMID- 7778994 TI - [Beta-hemolytic streptococcus endocarditis in an adolescent with hypertrophic cardiomyopathy]. AB - A 15 year-old male adolescent was hospitalized in a severe septic condition, due to infectious endocarditis which abided for 20 days. The admittance echocardiogram displayed a mitral valve vegetation in conjunction to a hypertrophic cardiomyopathy. In spite of applied antibiotics the patient expired. The authors emphasize the diagnostic difficulties of this compound entity and stress the need of antibiotic prophylaxis for patients who bear a hypertrophic cardiomyopathy, even in those with a non-obstructive disposition. PMID- 7778995 TI - [Percutaneous balloon aortic valvuloplasty in the newborn]. AB - Two cases of aortic valvar stenosis are presented, each of them submitted to balloon valvoplasty in the newborn period, with instant relief of the obstruction and clinical improvement. Studies about the aortic balloon valvuloplasty are being accomplished, showing results similar to the surgical approach, but with lower risks. PMID- 7778996 TI - [Rupture of sinus of Valsalva aneurysm]. AB - A 35 year-old man with aneurysm of the noncoronary sinus of Valsalva ruptured into the right atrium, detected by echodopplercardiogram and submitted to surgical correction is reported. The authors discuss peculiar aspects of this disease, with emphasis to the echodopplercardiographic diagnosis. PMID- 7778997 TI - [Case 5/94 (Instituto Dante Pazzanese de Cardiologia)]. PMID- 7778998 TI - [Cardiomyoplasty. A new Biotronik generator]. PMID- 7778999 TI - [Design, manufacturing, and testing of a pulsatile ventricular assist device]. AB - PURPOSE: To describe the design of a ventricular assist device (VAD), its manufacturing and testing. METHODS: The VAD is pulsatile, with a free floating membrane, smooth internal surfaces, and pericardium valves. It comprises also a pneumatic driving unit capable of operating in the "full to empty", EKG synchronized or asynchronous modes. The system was tested "in vitro" to assess its mechanical durability, hydrodynamic performance and hemolysis. "In vivo" tests were performed in 22 sheep and 8 calves aiming at optimizing cannulas and implant techniques. In these experiments, hemolysis and the device's capacity of restoring to normal hemodynamic parameters during induced cardiac failure were evaluated. RESULTS: The device was worked 4,000 hours without failure in a mock circulatory loop. Hydrodynamic performance was satisfactory for adult circulatory support. In "full to empty" mode it displayed a frequency mediated "Starling like" performance. Optimum output was achieved with a systole duration of 40% of the cycle. "In vitro" hemolysis index was 6.7 +/- 2.1. Hemolysis in animal experiments was clinically non significant. In calves under induced cardiac failure the VAD was able to normalize hemodynamic parameters within 120 minutes. CONCLUSION: This VAD is capable to circulatory assist for cardiogenic shock in conditions needed for an adult patient and the average time span anticipated for bridge to transplantation or post cardiotomy cardiogenic shock. PMID- 7779001 TI - [Mechanical assistance in cardiogenic shock after cardiac surgery]. PMID- 7779000 TI - [Human heart transplantation in Brazil]. AB - PURPOSE: To analyze patients operated on in Brazil from May 1968 until June 1993. METHODS: Three patients were transplanted in the historical period of 1968 and 1969. In the modern period from 1984-1993, 380 transplants were performed in 379 patients. These patients were transplanted in 23 services in 20 hospitals. These services are in 12 cities of 11 states. The state with the larger number of patients was Sao Paulo with 239 transplants followed by Minas Gerais with 58. RESULTS: In this casuistry, the patients were predominantly male (81%) with age between 31 and 40 years (30%). The most frequent indication was idiopathic dilated cardiomyopathy (53.4%) followed by ischemic (26.8%) and with a special reference for the Chagas' etiology (11%). The results in 297 patients showed 48 immediate and 49 late deaths. The actuarial survival curve showed 64.7% and 47.4% respectively after one and five years. CONCLUSION: Important differences were observed in relation to the international casuistry but even so benefits were present when compared with medical treatment. PMID- 7779002 TI - [Mechanical circulatory support as a bridge to cardiac transplantation]. PMID- 7779003 TI - [Cardiomyoplasty perspectives in the treatment of heart failure]. PMID- 7779004 TI - CAD/CAM/CAE in the medical engineering lab. PMID- 7779005 TI - Cardiomyoplasty: a summing up. PMID- 7779006 TI - 5th WAA Congress therapeutic artificial organs, 10 years after. AB - In 1983, more than 10 years ago, the concept of therapeutic artificial organs was proposed by this author. Currently developments of various types of immunomodulation technologies are well established, and therapeutic artificial organs for the treatment of autoimmunodiseases have become a well-accepted concept. It is this author's opinion that if we utilize apheresis technologies properly we should be able to prevent the aging process of mankind. Physical youth, and perhaps mental youth, can be achieved by apheresis technologies. However, in order to maintain youth and enjoy a high quality of life, it is essential to maintain a strong will to live. In this paper a new type of an artificial organ is proposed. This antiaging artificial organ is named "Juzo," the organ for a longer life, in Japanese, by this author. PMID- 7779007 TI - Present trends in clinical experience with dynamic cardiomyoplasty. AB - Dynamic cardiomyoplasty has been performed to reinforce the myocardium in the treatment of patients with severe cardiomyopathies. At the Heart Institute of Sao Paulo University Medical School, 36 patients were submitted to cardiomyoplasty between May 1988 and December 1993. The indications were idiopathic dilated cardiomyopathy in 31, ischemic cardiomyopathy in 3, and Chagas' disease cardiomyopathy in 2 patients. Twenty-eight patients were categorized in New York Heart Association (NYHA) Class III and 8 in Class IV despite the use of maximal medical therapy. There were no hospital deaths, and patients were followed up from 2 to 70 months (mean, 24 months). Besides the improvement of NYHA functional class from 3.2 +/- 0.6 to 1.6 +/- 0.9 at 6 months of follow-up, patients also presented significant changes in the left ventricular systolic and diastolic functions. Nevertheless, 16 patients died, and 2 patients were submitted to heart transplantation during late follow-up. Actuarial survival rates were 82.3% at 1 year, 61.5% at 2 years, and 38.8% at 5 years of follow-up. Otherwise, the analysis of factors influencing the outcome showed that long-term survival was significantly affected by preoperative functional class and by pulmonary vascular resistance. The 26 patients operated in NYHA functional Class III and with pulmonary vascular resistance below 4 Wood units presented survival rates of 72.7% at 2 years and of 63% at 5 years of follow-up. In conclusion dynamic cardiomyoplasty improves functional class and left ventricular function in patients with severe cardiomyopathies. However, the long-term survival after this surgical procedure may be limited by the patients' condition before the operation. PMID- 7779008 TI - Effects of muscle length, frequency of stimulation, and fatigue on the isometric tension in canine latissimus dorsi. AB - An experimental protocol was designed to study the mechanical response of the canine latissimus dorsi muscle stimulated to contract isometrically. Active and passive tensions were measured with the muscle's initial length varying within 10% of its physiologic length in situ. The force-frequency relationship was obtained at frequencies of stimulation of 1, 10, 15, 30, and 60 Hz. Muscle fatigability was assessed during 3 min of successive contractions. Tests were performed in pedicled muscles of anesthetized mongrel dogs (n = 10). Force-length characteristics were found to affect evoked tension markedly. Maximal active tension was generated near the muscle length in situ. Specific isometric tension measured with unit pulse stimulation was 2 +/- 0.4 N/cm2, and the time to peak twitch was 92.8 +/- 2.67 ms. With 60 Hz of stimulation frequency, the tension was 9.31 +/- 0.32 N/cm2, and the time to peak tension was 216.05 +/- 16.28 ms. After the fatigue test, the tension generated decreased to 62.5% of its initial value, and this decline was paralleled by the rate of tension development and tension relaxation. PMID- 7779009 TI - A feasibility study on a new artificial sphincter for colostomy. AB - Although many efforts have been put forth, fecal incontinence of colostomates is still an unsolved problem. Among the techniques available to improve continence, the use of electromagnetic/mechanical power has not been explored. Our work looks at the characteristics needed by the components of an artificial sphincter where the power of sphincteric muscles is substituted with electromagnetic/mechanical power, and the mechanical absence of muscles is replaced by a plastic band. Experimental work was done with isolated colon of 26 mongrel dogs, and all of them became continent by an intraluminal gas pressure over 80 mm Hg when a final perimeter between 3.7 and 4.7 cm was reached. No macroscopic lesions were noted on the guts' surface beneath the plastic band. The largest band displacement was 4.2 cm, and the traction force was under 50 N. PMID- 7779010 TI - Electrotactile stimulator for artificial proprioception. AB - With the goal of investigating artificial proprioception elicited by electrical stimulation, we have developed a tactile phi phenomenon-based stimulator. This two-channel microprocessed pulse amplitude modulation system generates two different envelope waveforms (triangular and elliptical) and allows programming and visualizing of its main parameters: pulse with (0.1-10 ms), pulse frequency (0.1-10 kHz), modulation frequency (0.3-10 Hz), current intensity (up to 20 mA), and the amplitude modulation index (0-100%). In vivo experiments with 5 normal persons have shown that it is possible to elicit a moving fused phantom image with good resolution. A triangular envelope is good for straight line sensations while the elliptical one is more comfortable and has better resolution for all kinds of moving images. PMID- 7779011 TI - An artificial neural system for closed loop control of locomotion produced via neuromuscular electrical stimulation. AB - The use of neuromuscular electrical stimulation for restoration of gait in spinal cord injured subjects has been seriously pursued by many investigators for the past 15 years. By and large, however, systems to date require the intervention of a person, be it the patient or an observer, and are restricted to control of stimulation onset and termination. Further, existing systems are not adaptable to environmental and patient variations. This work proposes a system that relies on neural computing to determine proper muscle activation patterns from biomechanical signals. The intelligent system is trained to perform gait under supervision, after which it can be used to control muscle stimulation in an unknown environment. Computer simulations suggest that the best neural architecture for control of gait is a neural network including units corresponding to movement history. Separate networks for the stance and swing phases, respectively, were found to work better than a single neural network trained on the entire gait cycle. The artificial neural device proposed here also includes a voice recognition system that will allow for voluntary locomotion. A safety circuit has been designed to preclude acceptance of unwanted vocal commands in the latter system. PMID- 7779012 TI - Effects of electronic autodefense devices on cardiac pacemakers. AB - The problem of interference on pacemakers as a result of extraneous electric current and electromagnetic fields is important since more than 1.5 million people worldwide have pacemakers implanted. Each year at least 100,000 people have cardiac pacemakers implanted. This article reports several effects of two electronic autodefense devices on some cardiac pacemakers. The results show that the interference affects severely the behavior of the cardiac pacemakers, but if the duration is no more than 5 s, the effects are not permanent, and the pacemakers return to the correct action as soon as the interference ceases. PMID- 7779013 TI - Hemodialysis versus continuous ambulatory peritoneal dialysis: effects on the heart. AB - In this study we compared the influence of 2 different modalities of treatment, CAPD and hemodialysis, on the prevalence and severity of left ventricular hypertrophy and cardiac arrhythmias of chronic renal failure patients. We compared 27 patients on the CAPD program with 27 patients on the chronic hemodialysis matched for sex, age, and duration of dialysis treatment. The prevalence of hypertension was significantly lower in CAPD than in hemodialysis patient (41% vs. 81%, p = 0.0023). Blood pressure levels were also lower in CAPD than in hemodialysis patients (systolic pressure 124.9 +/- 4.7 vs. 154.8 +/- 4.6 mm Hg, p < 0.0001; diastolic pressure 77.5 +/- 2.9 vs. 93.3 +/- 2.8 mm Hg, p = 0.0001). Left ventricular hypertrophy (LVH) was present in 52% of CAPD and in 93% of hemodialysis patients (p = 0.0008). Severe cardiac arrhythmias (Lown 3-4) occurred in only 4% of CAPD and in 33% of the hemodialysis group (p = 0.0149). The lower frequency of LVH in CAPD might explain the lower incidence of severe arrhythmias. PMID- 7779014 TI - Comparison of echocardiographic changes associated with hemodialysis and renal transplantation. AB - Long-term hemodialysis has been reported to cause progression of left ventricular (LV) hypertrophy with a tendency toward asymmetric septal hypertrophy. Renal transplantation is believed to reverse some of these changes. The aim of this prospective study was to compare the effects of long-term hemodialysis and of successful renal transplantation on cardiac structure and function assessed by echocardiography. Fifty-three patients were submitted to two echocardiographic evaluations separated by a 30 +/- 8 month interval. At the first control, all patients were on hemodialysis; at the second, 36 patients remained on dialysis while 17 had been submitted to renal transplantation. Age (44 +/- 13 vs. 40 +/- 10 years), gender (male, 50% vs 53%), and duration of dialysis at the initiation of the study (43 +/- 34 vs. 47 +/- 32 months) were comparable in the 2 groups. The prevalence of LV hypertrophy were 83% (first control) and 69% (second control) in the dialysis group and 82% and 71% in the transplant group. Comparisons between the two periods within each group showed that hemodialysis was associated with a significant reduction of the E/A ratio (1.25 +/- 0.4 vs. 1.02 +/- 0.4, p < 0.001) and systolic (155 +/- 28 vs. 137 +/- 26 mm Hg, p < 0.001) and diastolic (94 +/- 21 vs. 84 +/- 16 mm Hg, p < 0.05) blood pressure, and no change in LV mass index (171 +/- 51 vs. 156 +/- 43 g/m2, NS). In the transplanted group, there were reductions in the E/A ratio (1.42 +/- 0.6 vs 1.10 +/- 0.4, p < 0.05) and in LV diastolic dimension (50 +/- 7 vs. 46 +/- 5 mm, p < 0.05), but not in systolic (155 +/- 27 vs. 152 +/- 31 mm Hg, NS) or diastolic (97 +/- 11 vs. 97 +/- 20 mm Hg, NS) blood pressure. The LV mass index also did not change significantly (157 +/- 51 vs. 133 +/- 31 g/m2, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779015 TI - Mathematical model for a new mode of artificial ventilation: volume assisted pressure supported ventilation: a comparative study. AB - The patient submitted to artificial ventilation generally is connected to a high impedance flow source with controlled respiratory cycles to assure volume requirements or to a low impedance pressure source with spontaneous cycles to allow synchronization between his effort and system flow delivery. These two types of cycles represent the initial and final stages of artificial ventilation. The patient who needs a volume guarantee and at the same time presents unstable or insufficient inspiratory effort is difficult to manage with assisted cycles which are analogous to the controlled presence of a high impedance flow source. This paper presents a new approach where the respiratory cycles are obtained by the combination of flow and pressure sources using mathematical modeling. These cycles, named volume assisted pressure supported (VAPS) cycles, are compared with conventional assisted cycles showing a decrease in the patient work of breathing (WOB) during assisted ventilation. The theoretical results have been confirmed by clinical trials. PMID- 7779017 TI - Computational prediction of hemolysis in a centrifugal ventricular assist device. AB - This paper describes the use of computational fluid dynamics (CFD) to predict numerically the hemolysis in centrifugal pumps. A numerical hydrodynamical model, based on the full Navier-Stokes equation, was used to obtain the flow in a vaneless centrifugal pump (of corotating disks type). After proper postprocessing, critical zones in the channel were identified by means of two dimensional color-coded maps of %Hb release. Simulation of different conditions revealed that flow behavior at the entrance region of the channel is the main cause of blood trauma in such devices. A useful feature resulting from the CFD simulation is the visualization of critical flow zones that are impossible to determine experimentally with in vitro hemolysis tests. PMID- 7779018 TI - Design, manufacturing, and testing of a paracorporeal pulsatile ventricular assist device: Sao Paulo Heart Institute VAD. AB - This paper describes the design of a ventricular assist device (VAD), its manufacturing, and testing. The VAD presented is pulsatile, with a free-floating membrane, smooth internal surfaces, and pericardial valves. It comprehends also a pneumatic driving unit capable of operating in the "full to empty," EKG synchronized or asynchronous modes. In vitro tests were performed to assess its mechanical durability, hydrodynamic performance, and hemolysis. To optimize cannulas and implant techniques, we performed in vivo tests in 22 sheep and 8 calves. In these tests, we also evaluated hemolysis and the device's capacity to normalize hemodynamic parameters during induced cardiac failure. The VAD worked for 4,000 h without failure in a mock circulatory loop. In full to empty mode, it displayed a rate-mediated "Starling-like" performance. Optimum output was achieved with a systole duration of 40% of the cycle. The in vitro hemolysis index (IH) was 6.7 +/- 2.1. Hemolysis in animal experiments was clinically nonsignificant. In calves with induced cardiac failure, the VAD was able to normalize hemodynamic parameters within 120 min. PMID- 7779016 TI - Clinical comparison of blood oxygenators: a retrospective study. AB - The results for platelet count (PC), activated clotting time (ACT), postoperative bleeding, and hemoderivatives usage in cardiac surgeries were crossed against the type of oxygenator used. These were two bubble and one membrane type. A sample of the surgery population for each type was selected at random. Thus, the patients in this study were divided into 3 groups: BA: 87 patients, bubble oxygenator; BB: 87 patients, bubble oxygenator; M: 73 patients, membrane oxygenator. The groups were statistically similar (p > 0.05) for age, body surface area, cardiopulmonary bypass (CPB) time, and prevalence of cardiac disease. The rate of PC 15 min after CPB end and before its beginning was BA, 0.48 +/- 0.02; BB, 0.49 +/- 0.02; M, 0.55 +/- 0.03. The rate of ACT after protamine administration and before CPB was BA, 1.22 +/- 0.03; BB, 1.16 +/- 0.03; M, 1.16 +/- 0.03. Volume (ml) of total postoperative bleeding (POB) was BA, 904 +/- 72; BB, 963 +/- 73; M, 867 +/- 83. Patient percentage that used hemoderivatives (HD) was BA, 86.3%; BB, 88.5%; M, 90.0%. No statistical difference was found between groups (p > 0.05). This study indicates that although membrane oxygenators have better theoretic and experimental biocompatibility, no significant difference in PC, ACT, POB, and HD usage was observed in the clinical setting. All values are expressed as the mean +/- standard error of the mean. PMID- 7779019 TI - A paradigm for design of closed loop neuromuscular electrical stimulator control systems. AB - The use of neuromuscular electrical stimulation (NMES) for rehabilitation of gait in spinal patients is widely known. The best results can be obtained with the use of biomechanical sensors and a closed loop NMES system. One of the biggest problems faced in the design of control systems for closed-loop operation, in gait rehabilitation, is the variation of the mechanical conditions during the phases of gait. This work presents a new approach to ease the design of rule based closed loop systems for operation in conditions such as gait rehabilitation. PMID- 7779020 TI - Neural responses to electrical stimulation of the cochlea in guinea pigs. AB - A special bridge circuit was constructed to compensate stimulus artifact to determine the effects of an alternating current (AC) in the range of 3 to 20 kHz and direct current (DC) stimulation on the activity of cochlear nerve fibers. When AC and DC stimulation of the same fiber were compared, a greater current intensity was required to change the spike rate with AC stimulation than DC stimulation. While positive DC stimulation reduced activity, negative DC stimulation increased the spike rate. AC stimuli excited fibers in a manner similar to that observed with negative DC stimulation. Thresholds increased with stimulus frequency, suggesting that the effects of AC stimulation on the discharge rate are independent of the CF (characteristic frequency) of a fiber. The effects of short-time AC and DC stimulation on cochlear fiber activity lasted only during the stimulation, and the spontaneous activity did not significantly differ before and after electrical stimulation. PMID- 7779021 TI - Motile responses of isolated vestibular hair cells. AB - Vestibular sensory cells were isolated from the utricular macula or crista ampullaris of the guinea pig by enzymatic and mechanical dissociation. Isolated vestibular hair cells, especially type I hair cells, showed an active motile capacity. After exposure to a medium containing high concentration of potassium, or to a hypoosmotic medium, the type I hair cells showed tilting of their hair bundle to about 15 degrees. Given the tight and dense structure of the vestibular epithelium, the changes in shape of the isolated vestibular hair cells may in vivo lead to an influence of the mechano-sensitive stereocilia and modulate stiffness and compliance of the receptor structure as a whole including its cupular or macular relationship. This active mechanical events could be closely related to an active adaptation process. PMID- 7779022 TI - Atrophy of the tongue with persistent articulation disorder in myasthenia gravis: report of 10 patients. AB - Ten patients with atrophy of the tongue, from a group of 752 with generalized acquired myasthenia gravis (MG), were studied. Tongue atrophy developed late in the majority of patients and was accompanied by tongue paresis (70% of the cases) and eventually associated to atrophy of other muscles of the palate, especially the uvula. All the patients exhibited severe forms of MG with bulbar involvement, mainly persistent dysphonia and dysphagia, almost always refractory to treatment. There is no correlation among atrophy of the tongue, sex, and thymus pathology. There is correlation between severeness of symptoms and early, persistent and treatment refractory dysphonia and dysphagia. PMID- 7779023 TI - Mucociliary function of chronic inflammation in upper and lower airways. AB - Mucociliary function was examined to investigate the association of chronic inflammation in the upper and lower airways in four groups of subjects. They were composed of: 1) non-inflammatory subjects (control group), 2) patients with chronic sinusitis (S group), 3) patients with chronic bronchitis (B group), and 4) patients with chronic sinusitis and bronchitis (SB group). Mucociliary clearance (MCC), ciliary beat frequency (CBF) in the nose and left main bronchus and dynamic viscoelasticity (DVE) of these airway fluids were examined. Significant prolongation of nasal MCC in the S and SB groups were observed compared with the control group. CBF in the nose of the S, B, and SB groups were not different from that of the control group. DVE of nasal mucus in the S, B, and SB groups were higher than that in the control group. Significantly diminished bronchial MCC in the B and SB groups were observed compared with the control group. CBF of the bronchus was within normal range in all examined subjects. DVE of tracheobronchial mucus in the S, B, and SB groups were higher than that in the control group. It was suggested that high viscoelasticity of the tracheobronchial mucus in patients with chronic sinusitis and of the nasal mucus in patients with chronic bronchitis may be one of the causes of sinobronchitis. PMID- 7779024 TI - The contact Nd-YAG laser for oral and oropharyngeal malignant tumors. AB - Nine oral and oropharyngeal squamous cell carcinomas were removed with a contact Nd-YAG laser. Clinical and morphological studies on wound healing and effects of the Nd-YAG laser were performed. The wounds were not sutured and patients did not complain of any severe symptoms. The wound healing was prolonged to 3-6 weeks. Cells and glands degenerated at a depth of 2-3 mm by the direct effects of the laser. The epithelium exhibited acantholysis 5 mm from the site of laser injury. Scanning electron microscopy showed no coagulation or other coated material in the wound created by a surgical knife, while the wound surface by laser consisted of carbonization, well-coated and non-coated areas. These findings varied with the laser power. The coagulation and thermal effects of the Nd-YAG laser resulted in autolysis of tumor cells at least within 5 mm of the cutting surface. The contact Nd-YAG laser was useful for the removal of the malignant tumor in the oral cavity and oropharynx where it is difficult to maintain a generous safety margin. PMID- 7779025 TI - Tissue transmigration of CZON (Cosmosin) to middle ear mucosa, maxillary sinus mucosa, and palatine tonsils. AB - The concentration of CZON was determined by HPLC in surgical patients with chronic otitis media, sinusitis, and tonsillitis. One gram of CZON was injected intravenously prior to surgery. The time course of the mean tissue CZON level was as follows: In the middle ear mucosa, 3.7 micrograms/g at 15 min, 7.2 micrograms/g at 30 min, and 2.9 micrograms/g at 1 hr (the half life: 21.3 min). In the maxillary sinus mucosa, 10.5 micrograms/g at 15 min, 11.8 micrograms/g at 30 min, and 2.8 micrograms/g at 1 hr (the half life: 17.5 min). In the tonsils, 14.9 micrograms/g at 15 min, 9.3 micrograms/g at 30 min, and 2.0 micrograms/g at 1 hr (the half life: 13.2 min). The concentration was high in the maxillary sinus mucosa and the tonsils, but was low in the middle ear mucosa. In the formers the transfer ratio reached its peak 15 to 30 min after administration, but in the latter the peak was reached 30 to 60 min after administration. The order of the transfer ratio at each region was above 25%. The tissue concentration exceeded the MIC80s of frequent isolates from these infections. CZON is considered to be a highly useful drug in the treatment of these infections. PMID- 7779026 TI - Thyroid allograft after total thyroidectomy in a rat model. AB - The fact that in vitro culture of murine organ allografts prior to transplantation enhances graft survival is commonly accepted. In this study, we examined the possibility of thyroid allotransplantation for the therapy of total thyroidectomy in the rat model. Transplanted thyroid function was determined by 125I uptake ratio and evaluated by immunohistochemical and microautoradiographical assessments. Fully allogeneic thyroid glands cultured for 8-24 hr in Hank's balanced salt solution (HBSS) at pH 6.3 or 7.2 were transplanted to rats under the kidney capsule. Five weeks after allotransplantation, thyroid glands cultured for 16 hr in HBSS at pH 6.3 presented prolonged survival. This procedure could be used as an initial therapy not only for total thyroidectomized patients but also for patients with primary hypothyroidism. PMID- 7779028 TI - Malignant melanoma of the nasal cavity. AB - We report a case of amelanotic melanoma arising in the nasal cavity and paranasal sinuses, that could not be positively diagnosed as malignant melanoma before the patient's death in spite of repeated biopsies both from primary and metastatic lesions, including ultrastructural examination and immunohistochemical staining for S-100 protein with usual polyclonal antibody. The patient died of rapid wide spread dissemination of the tumor. In autopsy specimens, melanin pigment was detected, for the first time, by the Fontana's silver stain. The posthumous diagnosis of malignant melanoma was immunohistochemically confirmed for the specific antibodies, anti alpha-subunit of S-100 protein antibody and SK-46 (original antibody for melanoma made at the Department of Pathology, University of Gunma School of Medicine) from specimens obtained while alive. The application of a specific antibody for S-100 protein is recommended as useful for the diagnosis of malignant melanoma even when routine immunohistochemical procedures fail to demonstrate S-100 protein. PMID- 7779027 TI - Acute simultaneous bilateral vestibulocochlear impairment in neuro-Behcet's disease: a case report. AB - The central nervous system (CNS) is often a preferential target of Behcet's disease and diverse neurological manifestations have been described. Isolated hearing impairment or disequilibrium is also known to occur, but the simultaneous bilateral impairment of both vestibular and cochlear functions has been only rarely documented in Behcet's disease. A 52-year-old Japanese woman with neuro Behcet's disease had meningoencephalitis, a profound thrombocytopenia, and bilateral vestibulocochlear impairment during the acute exacerbation. Although the CNS involvement was apparent, the clinical history and neuro-otological findings pointed to bilateral inner ear involvement rather than the brainstem or the 8th nerve lesions. She has made an excellent clinical response to pulse-dose methylprednisolone therapy with improvement in her neurological symptoms and in arresting the acute deterioration of hearing loss, but repeated audiograms failed to maintain the improvement with a modest dose of oral prednisolone. Since the bilateral vestibulocochleopathy can be as incapacitating as oculopathy in Behcet's disease, an early detection and prompt instillation of adequate corticosteroid therapy may be mandatory, although not curative. PMID- 7779029 TI - Cervical neurofibroma in a patient with von Recklinghausen's disease. AB - A case of a huge cervical neurofibroma associated with von Recklinghausen's disease is reported. The patient with von Recklinghausen's disease was a 48-year old woman complaining of a rapidly growing mass around the neck for the last 6 months. In von Recklinghausen's disease, which corresponds to neurofibromatosis I, gigantic tumors around the neck often occur. The present case was classified as a plexiform neurofibroma which is derived from the peripheral nervous system, and this type frequently shows malignant change in contrast to other types of neurofibroma. In general, it is difficult to determine the origin of the nerve in cervical neurofibromas. A total extirpation of the tumor was done in our case, and revealed the nerve of origin to be the vagal nerve. Pathologically, H-E stained specimens showed that the tumor was a benign neurofibroma. However, immunostaining of the majority of the tumor cells were positive for PCNA. These results suggest that the tumor of our case possessed a low malignant potential. To date, neither local recurrence nor distant metastasis has been found on subsequent examinations. PMID- 7779030 TI - Primary papillary carcinoma of the thyroglossal duct: case report and review of the literature. AB - Primary malignancies of the thyroglossal duct are rare. Around 150 cases are described in the world literature, most of them being papillary thyroid carcinomas. Other types of tumors are squamous cell carcinomas, mixed follicular papillary carcinomas, or adenocarcinomas. Women are affected more often than men, the ratio being 2:1. Preoperative diagnosis of primary malignancies of the thyroglossal duct is uncommon. Initial treatment of primary malignancies of the thyroglossal duct is usually sufficiently done operatively by the so-called Sistrunk's procedure which, however, was first described in 1893 by Schlange. Some patients may need further treatment such as wider excision, thyroidectomy, radioiodine therapy, or neck dissection. In this report the case of a papillary carcinoma of the thyroglossal duct in a 63-year-old man is presented. It is intended to remind the reader of this pathology which is often forgotten because of its rarity. The problems that occur during the process of evaluation regarding ideal treatment of the individual case are discussed. The literature is reviewed. PMID- 7779032 TI - Inflammation and increased numbers of bacteria in the lower respiratory tract of horses within 6 to 12 hours of confinement with the head elevated. AB - Confinement of horses with their heads elevated for periods up to 24 hours was used to evaluate the extent and the effects of bacterial contamination of the equine lower respiratory tract. Significant (P < 0.05) increases in bacterial numbers (up to 10(9) colony forming units/mL in transtracheal aspirate derived samples) occurred within 6 or 12 hours in most horses. Pasteurella/Actinobacillus spp and Streptococcus spp were most commonly isolated. Lowering of the head for 30 minutes every 6 hours to facilitate postural drainage did not prevent multiplication of organisms to levels equivalent to those achieved by horses where the head was elevated for 24 hours. When horses were released from confinement and heads were no longer maintained in an elevated position, clearance of accumulated secretions and bacteria occurred within 8 to 12 hours. Thus, confinement with the head elevated resulted in significant bacterial contamination and multiplication within the lower respiratory tract during a period often encountered in routine management procedures, such as transportation. The clearance of accumulated secretions occurred over a prolonged period after release from such confinement. PMID- 7779031 TI - Acute febrile diarrhoea in horses: 86 cases (1986-1991). AB - Eighty-six horses presented for examination at the Rural Veterinary Centre between January 1986 to December 1991 with acute diarrhoea. The average age of affected horses was 3.2 +/- 0.2 years (mean +/- SE), with 69% three years or younger. Sixty-one horses were male (36 stallions, 25 geldings) and 83 horses were Thoroughbreds (47) or Standardbreds (36). Sixty-six horses were undergoing routine training at the time of onset of diarrhoea. Eight horses were afflicted with a non-specific illness within one to five days before the onset of diarrhoea, whereas eight horses developed diarrhoea during or within 48 h of discontinuation of antimicrobial therapy. Three horses developed the diarrhoea within 24 h of road transportation. Clinically, the disorder was characterised by a fever, sudden onset of profuse diarrhoea, clinical evidence of dehydration (estimated to be 5 to 12% of body weight at the time of admission) and shock. Degenerative leucopaenia, hyponatraemia, hypochloraemia, hyperkalaemia, hyperglycaemia and azotaemia were characteristic laboratory findings. Laminitis was a sequel in about 30% of cases. The cause of diarrhoea remained undetermined in most cases. Salmonellas were isolated from faecal or tissue samples in only two cases. Similarly, there was no evidence of seroconversion to Erhlichia risticii in 17 cases. Sixty-two of the horses survived the acute phase of the disease in response to supportive care. In horses that did not survive, necropsies were performed and revealed sanguineous or turbid peritoneal fluid. The colonic and caecal walls were oedematous and thickened with serosal congestion and discolouration of these organs evident grossly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779033 TI - Chronic vascular catheterisation of the koala and the rabbit. AB - Vascular access ports were surgically placed, first in rabbits maintained under laboratory conditions, and then in koalas maintained in a wildlife park. The ports remained patent for 9 months in rabbits and for up to 13 months in the koalas and were removed successfully. They allowed collection of blood samples without assistance or disturbance in koalas, and without stress as reflected by plasma cortisol concentration. The use of retention rings on the cannula tubing is recommended. PMID- 7779034 TI - Last occurrence and survival during winter of the arbovirus vector Culicoides brevitarsis at the southern limits of its distribution. AB - Linear regression analysis was used to describe the decline in numbers of Culicoides brevitarsis Kieffer into winter with monthly maximum, average and minimum temperatures at the southern limits to its distribution in New South Wales. From this, low temperature thresholds were derived when C brevitarsis would be absent from the field. The low minimum threshold +/- 2 SE (95% Confidence Interval) of 8.1 +/- 0.3 degree C was used with historical temperature data to estimate the last month that the species should occur (March to June) and the mean number of months (2 to 6.5) below the threshold at 17 selected sites. Probability for survival during winter at these sites was estimated from years when the number of consecutive months below the threshold was < or = 2 months. This varied from zero to 51% depending on the location of the site. Last occurrence was 0.7 months later on average and absolute probabilities for survival ranged from zero to 100% when the temperatures were increased by an arbitrary 2 degrees C. PMID- 7779035 TI - Bluetongue and Douglas virus activity in New South Wales in 1989: further evidence for long-distance dispersal of the biting midge Culicoides brevitarsis. AB - Infection of cattle with bluetongue and Douglas viruses was detected on the central and southern coast of New South Wales from January to April 1989. Bluetongue virus infection was found well south of areas of expected occurrence. Evidence is presented to support wind-borne dispersal of infected vectors, Culicoides brevitarsis, southwards from the Hunter Valley. PMID- 7779037 TI - Eimeria leuckarti infections in three foals. PMID- 7779036 TI - Production losses in Merino ewes and financial penalties caused by trichostrongylid infections during winter and spring. AB - The productivity of Merino ewes treated with ivermectin and a controlled-release capsule containing albendazole was compared with untreated ewes grazing the same pastures on each of 3 farms. Treated breeding ewes had significantly increased greasy fleece weights (GFW, 6.5% and 7.1%) compared with untreated breeding ewes, on 2 of 3 farms but treatment caused no significant increase in the GFW of non breeding ewes. Other benefits of treatment on all farms were a significant increase in body weight gain (from 1.7 to 3.7 kg) and a significant decrease in the weight of dag removed at crutching (from 42 to 622 g). These benefits occurred despite the presence on each farm of worms resistant to benzimidazoles. One disadvantage of treatment was an increase in mean fibre diameter of wool from treated ewes of from 0.12 to 0.41 microns. This increase reduces the value of the wool. Partial budgets indicated a net loss of from 8 to 62 cents per ewe for treatment. However, potential benefits such as increased growth rate and wool production from lambs of treated ewes were not included in the analysis. On one farm ewes were classified as 'susceptible' to severe dag if they had a dag score > or = 4 at the time of capsule treatment. Ewes classified as 'susceptible' were about 7 times more likely to develop severe dag than were other ewes. There was no significant difference between the GFW of untreated 'susceptible' ewes and untreated ewes not classified as 'susceptible'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779038 TI - Testing the concept of virally vectored immunosterilisation for the control of wild rabbit and fox populations in Australia. AB - Virally vectored immunosterilisation is a concept whereby a gene encoding an antigen from an animal's reproductive system is inserted into a virus and, during infection, stimulates the formation of antibodies to that antigen such that the animal is rendered infertile. There is good evidence that certain proteins from sperm or egg when introduced parenterally will induce infertility. This paper summarises the work of the Cooperative Research Centre for the Biological Control of Vertebrate Pest Populations and reviews progress toward the isolation of the genes for gamete antigens from rabbits and foxes and their introduction into suitable viral vectors as a means of control of these pests in Australia. PMID- 7779039 TI - Equine herpesvirus 1 HVS25A isolated from an aborted foetus produces disease in balb/C mice. PMID- 7779040 TI - Relationship between vitamin B12 and cobalt concentrations in bovine liver. PMID- 7779041 TI - Serological studies of bovine leukaemia virus infection in Queensland beef cattle. PMID- 7779042 TI - An encrusted cystitis caused by Corynebacterium urealyticum in a dog. PMID- 7779043 TI - Suspected traumatic rupture of the urinary bladder in an alpaca. PMID- 7779044 TI - Diarrhoea in Merino ewes during winter: association with trichostrongylid larvae. PMID- 7779045 TI - Neospora caninum--request for specimens for research. PMID- 7779046 TI - Treatment of superficial tumours on horses with dimethyl sulfoxide and cisplatin. PMID- 7779047 TI - Myocardial hibernation in terms of the flow-function relationship. PMID- 7779048 TI - Contractile pattern in acutely hibernating myocardium. PMID- 7779049 TI - Excitation-contraction coupling in hibernating myocardium. PMID- 7779050 TI - Critical role of energy supply and glycolysis during short-term hibernation. PMID- 7779052 TI - Myocardial hibernation. AB - From available results, the following schematic can be drawn: Reductions in perfusion pressure are not associated with impaired ventricular function as long as they take place within the autoregulatory range. Additional reductions in perfusion pressure that moderately diminish coronary blood flow will result in a particular ischemia with decreased but stable function: perfusion and contraction match, the myocardium hibernates. The process responsible for this new equilibrium could be termed down regulation of function. The trigger inducing hibernation is so far unknown. The strategy, however, is similar to that used by hibernating animals. Likewise, myocardial hibernation is a protective mechanism. As hibernators recover initial function after unfavourable periods are terminated, hibernating myocardium recovers after institution of physiologic perfusion. It is under debate, whether function quickly recovers or remains temporarily depressed. As hibernating animals might finally even die, if unfavourable periods last too long, myocardium might become irreversibly injured due to ischemia lasting too long. Additional reductions in perfusion pressure and oxygen supply below the hibernating range produce ischemia in the more classical sense, because oxygen supply and demand no longer match. Damage will become irreversible in case the situation persists longer than about 20 min. After onset of reperfusion, the myocardial function would remain depressed, however, for a considerable period: myocardial stunning. Considering the regional heterogeneities of myocardial blood flow, distinct differentiation between moderate and severe ischemia is difficult. Ischemia will induce more articulate damage in subendocardial than in subepicardial layers. Similarly, damage in the ischemic core will be more pronounced than in the border zone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779051 TI - Hibernating myocardium: a hypometabolic state for energy conservation. PMID- 7779053 TI - Acute adaptation to ischemia: short-term hibernating myocardium. PMID- 7779054 TI - Myocardial hibernation: unresolved physiological and clinical issues. PMID- 7779055 TI - Hibernating myocardium. PMID- 7779056 TI - Hibernating myocardium: a brief article. PMID- 7779057 TI - Myocardial hibernation, stunning, or both? PMID- 7779058 TI - Structural aspects of the chronic hibernating myocardium in man. PMID- 7779059 TI - Hibernating myocardium: adaptation or degeneration? PMID- 7779060 TI - The hibernating myocardium: identification of viable myocardium in patients with coronary artery disease and chronic left ventricular dysfunction. PMID- 7779061 TI - Hibernating myocardium represents a primary downregulation of regional myocardial oxygen consumption distal to a critical coronary stenosis. PMID- 7779062 TI - Commentary on hibernating myocardium and its clinical relevance. PMID- 7779063 TI - Hibernating myocardium, a clinical entity. PMID- 7779064 TI - Identification of "hibernating myocardium" by imaging approaches. PMID- 7779065 TI - alpha-adrenergic responses of isolated canine coronary microvessels. AB - Although alpha-adrenergic activation is known to increase coronary microvascular resistance in vivo, the magnitude of its segmental microvascular consequences is not well understood. Quantification of these effects in vivo is hindered by escape mechanisms that minimize the influences of constrictors, and alterations in flow and pressure, which effect microvascular tone by shear stress-dependent and myogenic mechanisms, respectively. To eliminate these confounding influences, we have studied responses in vitro under conditions with these variables controlled. We evaluated the diameter changes of isolated canine coronary arterioles (110 +/- 12 microns, n = 35) response to alpha-adrenergic activation by norepinephrine (10(-10) to 10(-4) M) in the presence of beta-adrenergic blockade by alprenolol (10(-6) M). In contrast to the situation in vivo, alpha adrenergic activation did not constrict isolated coronary arterioles, but constricted isolated coronary venules in a dose-dependent manner over a range of 10(-10) to 10(-4) M (-27 +/- 3% maximum diameter change). Coronary arteriolar alpha-adrenergic constriction was not promoted by 1) subthreshold or vasoactive doses of the vasoconstrictors KCl, angiotensin II, U46619, endothelin-1, neuropeptide Y or arginine vasopressin, 2) inhibition of the presynaptic uptake of norepinephrine by imipramine (10(-6) M), 3) inhibition of EDRF synthesis by NG monomethyl-L-arginine (10(-5) M) or 4) inhibition of prostaglandin synthesis by indomethacin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779066 TI - No adrenergic constriction in isolated coronary arterioles? PMID- 7779068 TI - Myocardial hibernation: relationship to a model for segmental dyskinesis. PMID- 7779070 TI - Prevention of bovine ketosis with glucogenic substance and its effect on fertility in Finnish dairy cows. AB - To avoid a harmful peak of negative energy balance, 200 ml of a 50% propylene glycol and 1% nicotinic amide solution were given twice a day to dairy cattle for ten days starting at day 14 post partum (p.p). Acetone content in milk was used as an indicator of energy balance and fertility was used as an indicator of the efficiency of the treatment. In addition, other factors affecting fertility were evaluated. During the prevention period, the acetone level in the prevention group (N = 31) decreased from 0.40 +/- 0.1 O mmol/l to 0.23 +/- 0.06 mmol/l (p = 0.09), but in the control group (N = 35) it increased from 0.23 +/- 0.04 mmol/l to 0.43 +/- 0.29 mmol/l acetone from the beginning to the end of the trial (p > 0.10). At day 50 p.p., however, the acetone levels in the two groups were the same. The treatment did not prevent clinical ketosis. Clinical ketosis tended to be associated with impaired fertility; in contrast, cows in the prevention group treated for ketosis had high fertility. A high daily milk yield at the first monthly recording test as well as high annual milk, fat and protein yields were correlated with the interval from calving to conception, r = 0.33, r = 0.50, r = 0.37 and r = 0.47, respectively. A low percentage of annual milk protein and at test 1 was significantly correlated with a long interval from calving to conception, r=-0.31 and r=-0.45, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779067 TI - Alpha 1-adrenergic tone does not influence the transmural distribution of myocardial blood flow during exercise in dogs with pressure overload left ventricular hypertrophy. AB - This study was carried out to test the hypothesis that alpha 1-adrenergic activation during exercise causes preferential vasoconstriction of subepicardial coronary resistance vessels, thereby augmenting blood flow to the subendocardium. Studies were performed in 7 dogs in which left ventricular hypertrophy was produced by banding the ascending aorta at 6-9 weeks of age. Animals were studied at approximately 1 year of age when the left ventricular/body weight ratio was 7.7 +/- 0.3 g/kg (mean +/- SE). Left anterior descending (LAD) coronary artery flow was measured with a Doppler velocity flow probe at rest and during a three stage graded treadmill exercise protocol. The transmural distribution of myocardial blood flow was assessed with radioactive microspheres. Coronary blood flow increased progressively as a function of heart rate and rate-pressure product in response to exercise. In contrast to normal dogs which maintain preferential blood flow to the subendocardium (ENDO) relative to the subepicardium (EPI) during exercise, the ENDO/EPI flow ratio in the hypertrophied left ventricles was 0.88 +/- 0.10 during exercise. Selective alpha 1-adrenergic blockade by infusion of prazosin (10 micrograms/kg) into the LAD decreased mean aortic pressure during exercise from 86 +/- 6 to 76 +/- 4 mmHg (p < 0.05), but did not change coronary pressure, heart rate, left ventricular systolic or enddiastolic pressures, or LVdP/dtmax. Coronary blood flow was not significantly altered by prazosin at rest, but was progressively increased during increasing levels of exercise levels. During the heaviest level of exercise prazosin caused a 22 +/- 3% increase in mean myocardial blood flow which was similar in all transmural layers, with no change in the transmural distribution of perfusion (ENDO/EPI = 0.85 +/- 0.09). These findings demonstrate that alpha 1-adrenergic vasoconstrictor tone limits blood flow during exercise in the hypertrophied left ventricle, but do not support the concept that alpha 1-adrenergic activation augments perfusion of the subendocardium during exercise. PMID- 7779069 TI - [Physiologic parameters and locomotor activity in Fleckvieh and Schwarzbund cattle during an alpine summer]. AB - The investigation on an alpine pasture was performed on 15 heifers of the breeds Fleckvieh and Friesians from different farms. Some physiological parameters and locomotor activities in dependence of breed, farm of origin and weather conditions were studied. Animals of one farm were pastured in spring, the animals of the other farm were brought directly from the barn to the mountain area. Physiological parameters were influenced by farm, but not by breed. The activities of GOT and CK increased in unprepared heifers only (due to the release from skeletal muscles) as did levels of free fatty acids and beta-hydroxybutyrate obviously due to adaptation-difficulties linked with energy-deficiency. Pre pastured animals showed higher blood-urea concentrations, due to their ability to locate always fresh grass with high protein content. The breed influence on the daily number of steps and on the distance covered was statistically not significant. Animals already pastured in spring showed more movement than unprepared ones. Among weather conditions thunderstorm showed a striking increase in activity which resulted from the search for shelter. On rainy days without wind the animals showed least movement. Cloudy, dry weather as well as sunshine was associated with average activity. These reactions to meteorological conditions were manifested more clearly in prepared heifers. The other animals obviously had to learn first how to minimize untoward effects by suitable behaviour. PMID- 7779072 TI - [The occurrence of Listeria monocytogenes in fecal samples of pigeons]. AB - Listeria spp. were isolated from faeces samples from 12 (3.4%) of 350 pigeons examined. Three isolates were identified as L. monocytogenes (1x serovar 1/2a, 1/2b, and 4ab), eight isolates were L. innocua (2x serovar 6a, 6x serovar 6b), and two isolates L. seeligeri (serovar 6b). One fecal sample yielded a mixed culture of L. monocytogenes and L. innocua. The results indicate that pigeons are not important in the epidemiology of listeriosis in man and animals. PMID- 7779071 TI - Assessment of safety and protective value of a cell culture modified strain "C" vaccine of hog cholera/classical swine fever virus. AB - The protective value of a commercial strain "C" vaccine of classical swine fever (CSF) was tested in weaner pigs. Vaccinated animals were challenged intranasally with the virulent hog cholera virus (HCV) strain ALFORT/187 in groups of four pigs each at one to four weeks post vaccination, respectively. Non-vaccinated control animals were challenged in the same manner. Some vaccinated pigs seroconverted as early as one week post vaccination with all pigs yielding neutralizing antibodies (nAb) against the vaccine virus at two weeks post vaccination. After challenge no clinical signs were observed in any of the vaccinated animals whereas non-vaccinated control animals developed fever starting in general on the fourth day post challenge. In vaccinated pigs no challenge virus could be isolated from leucocyte samples taken on days 3 to 7 post challenge while HCV was isolated from buffy coat leucocytes of all non vaccinated animals. Six out of eight control animals were sacrificed and viral antigen was detected in tonsils, mandibular lymph node and spleen in four animals, exclusively in tonsils in one animal and none in another animal. Two non vaccinated animals that survived the experiment seroconverted after challenge and developed nAb against the HCV strain ALFORT/187. PMID- 7779073 TI - [The specificity of antibodies reacting with Salmonella antigens in ELISA]. AB - Among cattle sera from herds without a history of salmonellosis and without vaccination against salmonellas, we sometimes found samples which reacted positively in the ELISA with salmonella antigen. Contrary to antibodies caused by a proved salmonella infection, these antibodies could be eliminated by a whole cell lysate of E. coli. In the colostra of cows which had received a salmonella live vaccine orally in the first days of life but were raised and kept without known exposition to salmonellas, we also found antibodies which reacted in the salmonella ELISA. They could not be eliminated by E. coli lysate. PMID- 7779074 TI - [The peripartal disease complex of the sow in the industrial swine breeding facility. 4. The effect of prophylactic oral medication on the occurrence of the peripartal disease complex of the sow with the symptoms of urinary tract infection and vaginal-vulvar discharge]. AB - In an industrial pig production unit 20 sows were selected at random. All the sows had a puerperal disease in their anamnesis. The sows were divided in two groups consisting of ten sows each. Group 1 received Ampicillin per os (3 g per sow and day) four days a.p. and four days p.p. The majority of the sows showed a significant E. coli bacteriuria and non of the sows showed a significant Enterococcus bacteriuria prior to treatment. The development of puerperal disease was registered. The treated group showed less occurrence of disease compared to the control. Group 1 revealed significant (p < 0.05) less early postnatal losses than the untreated control. Group 1 showed better four weeks weaning weights as well. It is the authors opinion that sows having significant bacteriuria a.p. should be treated a.p. and p.p. before periparturient disease occurs. PMID- 7779075 TI - A regulatory element in the 5'UTR directs cell-specific expression of the mouse alpha 4 gene. AB - Transfection experiments showed that the mouse alpha 4 promoter contains a downstream element in its 5'UTR which is essential for efficient promoter activity. DNaseI footprinting and electrophoretic mobility shift assays (EMSA) demonstrated that the region from nt +113 to +148 can bind a cell type-specific factor (MIII-3) present in the alpha 4m expressing cell line L1210 but not in the non-expressing cell lines A9 and LMTK. Two consensus SP1 sites in this 5'UTR were recognised in L1210, A9 and LMTK, and with extracts from A9 and LMTK, an AP2-like protein was shown to bind a downstream AP2 site. Thus both ubiquitous and cell type-specific factors regulate the expression of alpha 4m. PMID- 7779076 TI - A chicken Wnt gene, Wnt-11, is involved in dermal development. AB - We have isolated a new member of the Wnt gene family, Wnt-11, from chick embryo cDNA library and examined the expression pattern during embryogenesis by in situ hybridization. The Wnt-11 gene encodes Cys-rich secretory protein distantly related to Wnt-1 through Wnt-8 from the mouse and Xenopus. Expression of the Wnt 11 gene became evident at stage 14 in the dorsolateral region of somites and gradually restricted to the dermatome at stage 19 and later. In contrast to the other Wnt genes, Wnt-11 was not expressed in the neuroepithelium throughout stages 14-26. At stage 24 and later, Wnt-11 was expressed in the subectodermal mesenchyme of the limb and feather buds. The unique expression pattern of Wnt-11 in the paraxial mesoderm and dermatome suggests that Wnt-11 may play an important role in dermal development. PMID- 7779077 TI - HIV-1 gp120 produces DNA fragmentation in the cerebral cortex of rat. AB - In the present experiments we have used morphological techniques to study the neuropathological profile of the brain of rats after intracerebroventricular (i.c.v.) injection of recombinant HIV-1 gp 120. Using brain cryostat sections (10 microns) from rats treated with a single, daily dose of gp120 (100 ng/rat) given for 7 and 14 consecutive days, in situ DNA fragmentation was revealed in the neocortex but not in the hippocampus by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL). In these rats, dark degenerating neurones were observed in the neocortex but not in the hippocampus. Treatment with bovine serum albumin (300 ng/rat, i.c.v.) for up to 14 days did not produce DNA fragmentation nor did it yield neuropathological lesions of the neocortex or hippocampus. In conclusion, the present data demonstrate that gp 120 given i.c.v. produced DNA fragmentation in the neocortex, thus suggesting that apoptosis is the mechanism through which neurones of the neocortex are killed. PMID- 7779078 TI - Leukemia inhibitory factor (LIF) enhances trophoblast differentiation mediated by human chorionic gonadotropin (hCG). AB - We investigated the effect of LIF on the differentiation of trophoblasts. Isolated cytotrophoblasts were cultured with and without LIF and cell smears were immunocytochemically analyzed, using anti-hCG antibody. The percentage of differentiated trophoblasts stimulated by 10ng/ml of LIF was about 2.5-fold that in the control culture. The effect of LIF in inducing the differentiation of cytotrophoblasts to syncytiotrophoblasts was dose-dependent. The same effect was shown when hCG was added to the medium. This enhancing effect of LIF on trophoblast differentiation was blocked by adding anti-hCG antibody to the culture system. These results indicate that LIF enhanced trophoblast differentiation by stimulating hCG production in trophoblasts, and not by exerting a direct effect on the trophoblasts. PMID- 7779079 TI - Sequence and structural homologies between M. tuberculosis chaperonin 10 and the MHC class I/II peptide binding cleft. AB - The peptide corresponding to the C-terminal half of M.tuberculosis hsp10 was synthesised based on the prediction that it might represent an independent structural region of the protein. This hypothesis was confirmed by aggregation and CD studies using this peptide and longer sequences of the protein. The peptide shares about 40-50% sequence homology with alpha 2 and beta 1 chains of MHC class I and II antigens. This and the CD results which indicated that the peptide at acidic pHs folds into an anti-parallel beta-sheet were used to generate a 3D model which has the same "W" fold contained in the MHC peptide binding groove. These data suggest that the hypothesis of molecular mimicry proposed to be one of the mechanisms which triggers autoimmune diseases may be extended to hsp10 proteins. Furthermore the suggested evolutionary relationship between hsp's and MHC antigens may find support from these data. PMID- 7779080 TI - The novel aldehyde dehydrogenase gene, ALDH5, encodes an active aldehyde dehydrogenase enzyme. AB - The mRNA for the novel aldehyde dehydrogenase 5 (ALDH5) gene was detected in HuH7 hepatoma cells. The cells also expressed cytosolic aldehyde dehydrogenase (ALDH1) mRNA, but no mitochondrial aldehyde dehydrogenase (ALDH2) mRNA. Extracts of the hepatoma cells contained an enzymatic activity with an isoelectric point similar to that of ALDH1. This enzyme activity was insensitive to inhibition by disulfiram, a potent inhibitor of ALDH1. The enzyme was active with short chain aldehydes (acetaldehyde and propionaldehyde) and NAD+, but not with NADP+, and the activity was higher in the mitochondrial pellet than other cell fractions. These studies demonstrate the expression of ALDH5 mRNA in a human hepatoma and suggest that the gene product is enzymatically active and probably resides in the mitochondria. PMID- 7779081 TI - Activation of mitogen-activated protein kinase by the human prostaglandin EP3A receptor. AB - Mitogen-activated protein (MAP) kinases are involved with cellular proliferation, and while the traditional activators of these kinases have been the growth factor receptors, recent data indicate that G-protein coupled receptors which inhibit adenylyl cyclase can activate MAP kinases as well. We have recently cloned an alternative splice variant of a human receptor for prostaglandin E2 (PGE2) which inhibits adenylyl cyclase and as been defined as the EP3A (Brit. J. Pharmacol. 112:377, 1994). In the present study the ability of this receptor to activate MAP kinase was examined. In crude lysates of COS-7 cells transfected with the human EP3A, 1 microM PGE2 stimulated MAP kinase activity approximately 1.3-fold with an EC50 of approximately 6 nM. Ion exchange chromatography followed by immunoblot analysis showed that the stimulation of MAP kinase activity co-fractionated with immunoreactive MAP-2 kinase (ERK1). This activation of MAP kinase activity by the EP3A receptor may explain the proliferative actions of PGE2 in some tissues. PMID- 7779082 TI - Potent inhibitors of the HIV-1 protease with good oral bioavailabilities. AB - A series of novel pseudo-symmetrical and unsymmetrical inhibitors based on the backbone modification of a peptidomimetic were synthesized and found to be highly potent inhibitors of the HIV-1 protease (IC50 = 2.9 to < 0.5 nM). These compounds also possess good antiviral activity in vitro as measured by inhibition of the cytopathic effect of HIV-1(3B) in MT-4 lymphocytes. Importantly, some of these compounds also have good oral bioavailabilities in rats (F = 30.6% to 100%). One of these compounds 4C, also has good oral bioavailability in beagle dogs and cynomolgus monkeys. PMID- 7779084 TI - Telomere repeat fragment sizes do not limit the growth potential of uterine leiomyomas. AB - We have compared the length of telomere repeat fragments (TRF's) in 19 uterine leiomyomas from 6 patients with the corresponding myometrium. The advantage of this study of TRF length is that cells from uterine leiymyoma and cells from corresponding myometrium do not contain any considerable proportions of other cells as revealed by analysis of clonality. In all tumor samples a loss of TRF length ranging from 1120 to 4690 bp was noted. There was no correlation between tumor volume or size of tumor population as revealed by histological examination and loss of TRF length. From the obtained TRF length data (an average myometrial TFR length of 13 kb and an average loss of TRF length in myoma cells of 83 bp per cell division) we concluded that TRF length reduction does not limit the growth potential of uterine leiomyomas. PMID- 7779083 TI - ATP induces dissociation of the 90 kDa heat shock protein (hsp90) from F-actin: interference with the binding of heavy meromyosin. AB - The 90 kDa heat shock protein (hsp90) is a major cytoplasmic molecular chaperone associating with various other proteins such as steroid receptors, protein kinases and filamentous actin. hsp90 has also been shown to bind ATP, which causes a conformational change of the protein. The physiological role and significance of ATP binding by hsp90, however, has remained unclear. Here we show through direct, microscopic observations, that ATP induces the dissociation of actin filaments from immobilized molecules of hsp90 as well as the dissociation of F-actin from heavy meromyosin in the presence of hsp90. PMID- 7779085 TI - EPR and redox characterization of ferredoxins I and II from Desulfovibrio vulgaris Miyazaki. AB - Detailed redox titrations monitored by EPR and UV-visible spectroscopies have been carried out on the dimeric ferredoxins I and II from Desulfovibrio vulgaris Miyazaki. Ferredoxin II contains a unique [4Fe-4S] cluster per subunit characterized by a midpoint potential of -417 mV at 24 degrees C. The enthalpic and entropic contributions to the redox free energy variation of this cluster have been determined from the temperature dependence of the midpoint potential and compared to the data reported for other iron-sulfur proteins. The molecular arrangement of the two subunits is such that two [4Fe-4S]i+ clusters are magnetically coupled in the fully reduced state of the protein. Ferredoxin I contains one [3Fe-4S] and one [4Fe-4S] cluster per subunit, whose spectral and redox properties are very similar to those of the same clusters in ferredoxin III from Desulfovibrio africanus. The strong heterogeneity in the redox properties of the [3Fe-4S] center supports a bridging position between the N-terminal and C terminal parts of the protein. PMID- 7779086 TI - Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain. AB - Mutations involving the transmembrane domain of the thyrotropin receptor (TSHR) confer constitutive activation of the receptor and can cause human diseases. Naturally occurring activating mutations identified to date are located only in the transmembrane domain of the receptor. We now report a mutant involving the extracellular domain of the TSHR which also shows constitutive activation. This mutation is missing residues 339-367 located in the C-terminal portion of the extracellular domain. When expressed in COS-7 cells, the mutated TSHR (M3B) retained similar TSH binding ability to that of the wild-type receptor. However, the basal cAMP production without TSH stimulation in COS-7 cells transfected with M3B cDNA was significantly higher than that of COS-7 cells with wild-type receptor, indicating that the mutant receptor is constitutively activated. Our results provide new insight into the mechanism of receptor activation. PMID- 7779087 TI - Cloning of rat and mouse P2Y purinoceptors. AB - The cellular responses to ATP are mediated by specific high-affinity receptors designated as P2 purinoceptors, five subclasses of which have been defined pharmacologically-P2X, P2Y, P2U, P2T, and P2Z. A cDNA clone encoding a rat P2Y purinoceptor was isolated from an insulinoma cDNA library. The 373-amino acid rat P2Y purinoceptor sequence has 85.7% and 37.8% identity with chicken P2Y and rat P2U purinoceptors, respectively. The sequence of the mouse P2Y purinoceptor was also determined and there was 97.1% amino acid identity with the corresponding rat sequence. RNA blotting studies showed that rat P2Y purinoceptor mRNA was expressed at variable levels in many tissues including heart, brain, spleen, lung, liver, skeletal muscle and kidney, although it was not detected in testis. The cloned rat P2Y purinoceptor was expressed in Xenopus laevis oocytes and possessed the properties expected for this receptor subtype. PMID- 7779088 TI - Direct measurement for elasticity of myosin head. AB - During muscle contraction, chemical energy from ATP hydrolysis is converted to the relative sliding movement of actin and myosin filaments. In order to elucidate the molecular mechanism of sliding-force generation, it is a crucial clue to know an elastic modulus of myosin. Here, we report direct measurements of Young's modulus of myosin head (myosin subfragment-1) isolated from rabbit skeletal muscle, using a surface forces apparatus. Our results show that the elasticity of myosin subfragment-1 has direction and is about 0.3 GPa along the long axis during ATP hydrolysis. When the bow-shaped subfragment-1 is modelled as an elastic rod, the stiffness and the bending fluctuations of subfragment-1 are calculated to be 3-7 pN/nm and about 1 nm, respectively. These results strongly support a model of multiple power strokes rather than the conventional tilting crossbridge model. PMID- 7779089 TI - The human bradykinin B2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region. AB - Hybridization of Northern blots with a probe corresponding to the coding region of the bradykinin B2 receptor revealed a single transcript of approximately 4.0 kb. Using the same probe, we detected a 2.6 kb human cDNA clone that overlapped 103 bp with the 3' end of the known coding region and contained a classical polyadenylation site and a polyA tail. The gene for the human B2 receptor was isolated from a human placenta genomic library. Analysis of several genomic lambda clones indicated that the B2 receptor gene is organized in three exons. Genomic Southern analysis revealed the B2 receptor to be encoded by a single copy gene. In situ hybridization showed that the gene is located on chromosome 14q32. By testing different putative regulatory fragments in a luciferase reporter assay, a gene activating function of the 5' upstream region of exon 1 was demonstrated. PMID- 7779090 TI - Identification of polymorphic sites of the human bradykinin B2 receptor gene. AB - The characterization of the genomic organization of the B2 bradykinin receptor gene enabled us to systematically search for polymorphic markers in this gene in a South German cohort (N = 179). We identified at least three polymorphic sites in each of the three exons existing: (i) in exon 1 next to the promoter region, a tandem repeat polymorphism consists of three common alleles, (ii) in exon 2 at nucleotide position 181 of the cDNA a C to T transition leads to an aminoacid substitution from arginine to cysteine in the receptor protein at position 14 (R14C), and (iii) a more complex repeat polymorphism, located in the 3' not translated region of exon 3, comprises at least two common alleles and two rare variants. These new genetic markers provide valuable tools to elucidate a potential role of a hereditary dysfunction of the B2 bradykinin receptor gene in disorders such as hypertension or ischemic heart disease. PMID- 7779091 TI - Angiotensinogen gene expression is induced by cyclical mechanical stretch in cultured rat cardiomyocytes. AB - The effect of cyclical mechanical stretch on angiotensinogen gene expression was examined using a neonatal rat cardiocyte culture system. Cultured cardiocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. The angiotensinogen gene was activated 2 to 5 fold after stretch for 3 to 24 hr, as shown by quantitative reverse transcription polymerase chain reaction. The 5'-flanking region of the angiotensinogen promoter was activated after stretch for 24 hr. This gene expression could be completely suppressed by losartan, a specific antagonist of angiotensin II receptor. These results indicate that (1) cyclical mechanical stretching of cardiocytes is a good model for the study of cardiac hypertrophy-related gene expression; (2) cyclical stretch up-regulates expression of the angiotensinogen gene and (3) the increase in promoter activity may contribute to the induction of angiotensinogen mRNA by cyclical stretch. PMID- 7779092 TI - Expression of the endothelin-converting enzyme gene in human tissues. AB - Based on the cDNA sequence of the human and bovine endothelin converting enzyme (ECE-1) we have developed a novel reverse transcription polymerase chain reaction to investigate the tissue expression of this gene. We were able to specifically detect the gene mRNA starting from very limited amount of tissue in all human as well as bovine tissues examined. Thus, our results confirm a widespread expression of the ECE-1 gene in human tissues, in keeping with the findings in other species, and suggest a major biological role of ECE-1. PMID- 7779093 TI - Transcription initiation is localized to a TATAless region in the ovine beta 1 adrenergic receptor gene. AB - We cloned and sequenced the ovine beta 1 adrenergic receptor (beta 1AR) gene and promoter region. The transcription start site was localized by RNase protection and primer extension to a GC-rich region. The predominant initiation sequence did not resemble an initiator element and there was no upstream TATA box. Sequence analysis revealed several potential thyroid hormone and glucocorticoid regulatory elements. Identification of the promoter structure of this important gene will help define its novel regulation during development. PMID- 7779095 TI - Elucidation of the region responsible for EDTA tolerance in PQQ glucose dehydrogenases by constructing Escherichia coli and Acinetobacter calcoaceticus chimeric enzymes. AB - We constructed various chimeric PQQ glucose dehydrogenases (PQQGDHs) from an EDTA sensitive PQQGDH from Escherichia coli and an EDTA-tolerant PQQGDH from Acinetobacter calcoaceticus by homologous recombination of their structural genes. The EDTA tolerance of the resulting chimeric enzymes was investigated. Our results demonstrated that EDTA tolerance of PQQGDHs can be completely altered by substituting each corresponding region. The EDTA tolerance of A. calcoaceticus PQQGDH is mostly within a region composed of about 90 amino acid residues located between 45 and 56% of the distance from the N-terminal region. PMID- 7779094 TI - Formation of heparan sulfate or chondroitin/dermatan sulfate on recombinant domain I of mouse perlecan expressed in Chinese hamster ovary cells. AB - Recombinant domain I of mouse perlecan was expressed in Chinese hamster ovary (CHO K1) cells and affinity purified on Ni-agarose. Gel chromatography followed by characterization of glycosaminoglycans by the use of glycosaminoglycan lyases showed that the recombinant proteoglycans contained, on average, three glycosaminoglycan chains of heparan sulfate or chondroitin/dermatan sulfate of approximately 12 kDa median size. These data demonstrate that domain I has functional sites for attachment of glycosaminoglycans and indicate that the glycosaminoglycan chains of native perlecan are grouped at its N-terminal end. This, in turn, suggests that the likely function of domain I in perlecan would be to provide for the addition of glycosaminoglycan chains to the core protein. PMID- 7779096 TI - Dopamine transporter gene polymorphism and alcoholism. AB - In this search for a possible association between the dopamine transporter gene (DAT1) polymorphism and alcoholism, 655 Japanese alcoholics were grouped according to their aldehyde dehydrogenase-2 (ALDH2) genotypes. Because inactive ALDH2 is an established negative risk factor for alcoholism, alcoholics with the mutant allele, ALDH2*2, were considered a relatively homogeneous group. The frequency of the 7-repeat allele of the DAT1 variable number of tandem repeat was significantly higher in alcoholics with ALDH2*2 than in control subjects. These results are consistent with the hypothesis that alteration in the dopaminergic system plays some role in the development of alcoholism. PMID- 7779097 TI - Not Ca2+ but CAMP is the second messenger for morphological changes in rat megakaryocyte. AB - ATP and thrombin both induced Ca2+ mobilization from intracellular Ca2+ store site of megakaryocyte, the progenitor cell of platelet (Uneyama C., Uneyama H. and Akaike N. (1993) J. Physiol. (Lond.), 470, 73-749). Since in platelet, thrombin is known as a strong agonist and ADP is known as a weak agonist, we further investigated the effect of these agonists on megakaryocyte. Thrombin induced Ca2+ mobilization, 5-hydroxy tryptamine (5-HT) release and aggregatory morphological changes in megakaryocyte, but ATP induced only Ca2+ mobilization. Thrombin-induced 5-HT release was inhibited by adenylate cyclase-activating drugs, and the morphological changes could be induced by H-8, an inhibitor of cAMP-dependent protein kinase. These results suggest that the Ca2+ mobilization is not sufficient to induce morphological changes, and the signal to cause morphological changes in megakaryocyte may be cAMP. PMID- 7779098 TI - Molecular cloning and posttranscriptional regulation of macrophage inflammatory protein-1 alpha in alveolar macrophages. AB - Macrophage inflammatory protein-1 alpha (MIP-1 alpha) belongs to the "chemokine" superfamily of chemoattractant pro-inflammatory cytokines. MIP-1 alpha is chemotactic for monocytes and neutrophils and thus, plays an important role in initiation and control of inflammation. We have isolated and sequenced a cDNA clone encoding rat MIP-1 alpha. This 0.75 kb cDNA includes a single open reading frame of 92 amino acids. Expression of MIP-1 alpha mRNA was characterized in NR8383, a rat alveolar macrophage cell line (RAM). In resting RAM cells, MIP-1 alpha mRNA decayed rapidly, with a half life of less than 2 hours. Lipopolysaccharide (LPS) treatment of RAM cells resulted in a dose-dependent increase in MIP-1 alpha steady state mRNA expression. The induction of MIP-1 alpha mRNA by LPS was partially the result of mRNA stabilization, as half life increased to over 6 hours. PMID- 7779099 TI - Purification and characterization of Rab GDI beta from rat brain. AB - A new Rab GDI was purified from the synaptic soluble fraction of rat brain by several column chromatographies as a protein that inhibited the dissociation of [3H]GDP from Rab3A but was not recognized by an anti-Rab GDI alpha antibody. The partial amino acid sequence analysis revealed that it was identical with rat Rab GDI beta. Purified Rab GDI beta showed the kinetic properties similar to those of Rab GDI alpha, including the inhibitory effect on the dissociation of GDP from Rab3A, the substrate specificity, the requirement of the post-translational lipid modifications of Rab3A, the stoichiometric interaction with the GDP-bound form of Rab3A, the inhibitory effect on the binding of Rab3A to erythrocyte ghosts, and the stimulatory effect on the dissociation of Rab3A from the membrane. PMID- 7779101 TI - The influence of sterols on the sensitivity of lipid bilayers to melittin. AB - The sensitivity of planar lipid bilayers to the permeabalizing effect of melittin was evaluated when sterols of varying structure were incorporated into the membrane. The addition of increasing amount of cholesterol (0-50 mole %) decreased the sensitivity of membranes formed from negatively charged phospholipids to melittin but did not (in amount of up to 66 mole %) change the sensitivity of membranes formed from zwitterionic lipids. 7-Dehydrocholesterol, stigmasterol and ergosterol had the same ability as that of cholesterol to decrease the membrane sensitivity to melittin, while lanosterol had no effect on the sensitivity of membranes to melittin. The results suggest that the effect of sterols is complex and cannot be explained only by a direct interaction of melittin with cholesterol, by a decrease of membrane fluidity, or by changes in distribution of surface charge. PMID- 7779100 TI - Activation of membrane-bound phospholipase D by protein kinase C in HL60 cells: synergistic action of a small GTP-binding protein RhoA. AB - Regulation of phospholipase D (PLD) activation by protein kinase C (PKC) was studied in membranes isolated from human promyelocytic leukemia HL60 cells. The activation of membrane-bound PLD by PKC partially purified from rat brain was most effectively induced with phorbol 12-myristate 13-acetate (PMA) and Ca2+ (1 microM) which caused translocation of PKC to membranes. Ro31-8425, a potent inhibitor of PKC, suppressed the catalytic activity of PKC in a concentration dependent manner, with complete inhibition at 5 microM. However, the PKC-mediated PLD activation was not affected by Ro31-8425. It was thus suggested that membrane bound PLD of HL60 cells was activated by PKC translocation but probably via a phosphorylation-independent mechanism. Furthermore, addition by guanosine 5'-3-O (thio)trisphosphate (GTP gamma S) potentiated the PKC-mediated PLD activation and this potentiating effect was abolished by Rho GTPase dissociation inhibitor (RhoGDI). The suppressed PLD activation by RhoGDI was completely restored by addition of recombinant RhoA. These results indicate that the PKC-mediated PLD activation can be synergistically potentiated by RhoA in HL60 membranes. PMID- 7779102 TI - An extracellular inositol phospholipid-specific phospholipase C is released by cultured Swiss 3T3 cells. AB - A phosphatidylinositol-cleaving phospholipase C (PI-PLC) activity is released into the extracellular environment by intact Swiss 3T3 cell cultures. The activity is found in both serum-containing and serum-free defined culture medium. The cells remain attached and intact by Trypan Blue exclusion and lactate dehydrogenase assays. The activity is specific for phosphoinositides as no cleavage of phosphatidylcholine is observed. The activity is a phospholipase C rather than D since the water soluble products formed from cleavage of [3H]phosphatidylinositol were inositol phosphates and not inositol. Analysis of the inositol phosphate products showed a variation in composition with the pH of the assay, the ratio of noncyclic:cyclic forms being 60:40 at pH 7.5 and 40:60 at pH 5.5. This external phospholipase C resembles the well-characterized intracellular isozymes in that it is calcium-dependent and has a pH optimum between 5 and 6. From membrane filter assays the molecular weight of the native enzyme is estimated to be between 50 and 100 kDa. PMID- 7779103 TI - Telomere shortening in chronic liver diseases. AB - We measured the telomere length in patients with chronic hepatitis or liver cirrhosis and found a significant telomere shortening in the liver with chronic liver disease compared to that in the normal liver. The telomere length tended to decrease with the progression of chronic liver disease. PMID- 7779104 TI - Identification of brush border myosin-I in liver and testis. AB - Brush border myosin-I, or BBMI, constitutes the lateral links that connect in intestinal microvilli the core bundle of actin filaments to the membrane. Although related molecules have been identified in other higher eukaryotic tissues, northern blot analysis has indicated that the distribution of this particular myosin-I isoform is restricted essentially to intestine. Using reverse transcriptase polymerase chain reaction we have identified BBMI in a wide range of tissues including liver and testis. Our results also indicate that in testis the BBMI gene might be alternatively spliced. PMID- 7779105 TI - Acute endotoxin tolerance is accompanied by stimulated glucose use in macrophage rich tissues. AB - A single injection of E. coli LPS at a dose of 10 mg/kg b.w. ("high dose") is lethal in Sprague Dawley rats. However, animals given a sublethal dose of LPS (0.5 mg/kg bw; "low dose") at time zero, followed by a second high dose injection at 48 h, display endotoxin tolerance with 100% survival. The aim of the present study was to assess the relationship between this observed endotoxin tolerance and the endotoxin-induced glucose metabolic response in selected tissues and nonparenchymal hepatic cells. In each experimental group two injections, the first at time zero, the second at 48 h were given in vivo. Four experimental groups constituted these studies: A) saline followed by saline, B) low dose LPS followed by saline, C) saline followed by high dose LPS, and D) low dose LPS followed by high dose LPS. In vivo glucose use in tissues and cells was measured 3h after the last treatments employing the 2-deoxy-glucose tracer technique. Glucose use by liver, lung, spleen and intestine was not different between saline/saline (group A) and low dose LPS/saline injected (group B) animals. Saline/high dose LPS injection (group C) doubled glucose uptake, while the sequential LPS injections (group D) caused an additional, 2-3 fold increase in the glucose use by these tissues. Hepatic endothelial cells showed a similarly elevated glucose use in vivo in both group C and D. Kupffer cells from group D animals, however, displayed markedly elevated glucose use in vivo as compared to cells from group C. Our data indicate that high dose LPS in endotoxin tolerant animals is accompanied by a more markedly stimulated tissue glucose use than found following lethal LPS treatment alone. This increased peripheral glucose use may support cellular functions responsible for the protection of the host. PMID- 7779106 TI - Genomic cloning of the human histo-blood group ABO locus. PMID- 7779107 TI - Analysis of translational termination of recombinant human methionyl-neurotrophin 3 in Escherichia coli. AB - A highly efficient UGA stop codon readthrough event during the synthesis of human neurotrophin 3 in E. coli is described. The incorporation of a Trp residue at the UGA stop codon is confirmed combining both the chemical analyses and the molecular and genetic data in this report. The 3' adjacent nuleotide to the UGA stop codon plays a crucial role in determining the readthrough efficiency in the order of A > G > C > U. The replacement of UGA with UAA or UAG totally abolished this readthrough phenomenon and the use of StpR host cells also prevented the occurrence of UGA readthrough. Gene dosage (or plasmid copy number) effect was not indicated in this event; however, the titration of RF-2 by mRNA transcripts under over-expression conditions might explain why tRNAtrp competes so well with RF-2 for UGA. Another apparently less produced readthrough product resulting from a transcript with no stop codon is also recorded, and the addition of a second in frame stop codon increased the amount of the observed readthrough product. PMID- 7779108 TI - cis-splicing and polyadenylation of actin RNA can precede 5' trans-splicing in nematodes. AB - In nematodes many precursor RNAs undergo both cis-splicing (intron removal) and trans-splicing (spliced leader addition) via molecular mechanisms thought to be very similar. We examined the temporal order of trans- and cis-splicing by analyzing cDNAs of partially processed transcripts from an actin gene of the parasitic nematode, Onchocerca volvulus, which has five short introns. We found that in this model gene system trans-splicing can follow cis-splicing and polyadenylation, and we obtained no evidence for alternative pathways of splicing. This result is in contrast to the tubulin genes of African trypanosomes where trans-splicing precedes polyadenylation (1). PMID- 7779109 TI - Calreticulin is the major Ca2+ storage protein in the endoplasmic reticulum of the pea plant (Pisum sativum). AB - A 56kDa protein with high similarity in its N-terminal amino acid sequence to animal calreticulin and 100% homology with the N-terminal amino acids of spinach calreticulin has been identified in seeds of the pea plant (Pisum sativum). A new purification procedure is described by which the calreticulin-like protein was selectively solubilized by incubation with deoxycholate and HgCl2 from microsomes enriched for endoplasmic reticulum. Following Mono Q ion exchange chromatography of the deoxycholate extract by fast protein liquid chromatography, the calreticulin-like protein was obtained in nearly pure form. This purified protein is similar to animal calreticulin in apparent mass, characteristic blue staining with Stains-all dye and calcium-binding ability. In addition, this protein is recognized only by affinity purified antibodies against rabbit calreticulin and is not recognized by anti-calsequestrin antibodies. Our data suggested that calreticulin rather than calsequestrin functions as the Ca(2+)-storage protein in the endoplasmic reticulum of pea plants. PMID- 7779110 TI - Cyclodextrins as protein folding aids. AB - Aggregation of proteins is a frequent occurrence during their transition from random coil to native structure. The influence of cyclodextrins in the refolding of carbonic anhydrase under aggregating conditions was studied. Cyclodextrin prevented formation of protein aggregates during renaturation of carbonic anhydrase. In addition, over 90% of active enzyme was recovered even at protein concentrations as high as 67 microM. The enhanced protein reactivation by cyclodextrins may be due to their ability to bind to hydrophobic sites in protein folding intermediate(s) followed by their subsequent removal as the protein refolds. PMID- 7779111 TI - Antibodies to ICAM-1 protect kidneys in severe ischemic reperfusion injury. AB - ICAM-1 has been implicated in the pathophysiology of ischemic-reperfusion injury in a number of organs, but its role in mediating severe ischemic-reperfusion injury in the kidney has not been extensively studied. Uninephrectomized Sprague Dawley rats were pretreated with either control monoclonal antibody (mAb) or mAb to ICAM-1 and subjected to 60 min of renal artery occlusion. The serum creatinine, complete blood count and kidney histo-pathological damage scores (PDS) (Scale:0-4) were assessed prior to and 24 hours after ischemia. Mean serum creatinine (mg/dl) 24 hours after ischemia was significantly decreased in the anti-ICAM-1 group (1.38 +/- 0.23, p < 0.001) compared to control (2.87 +/- 0.34). PDS was also reduced in anti-ICAM-1 (2.55 +/- 0.20, p < 0.05) group compared to control (3.35 +/- 0.30). These data demonstrate that blocking ICAM-1 significantly mitigates severe ischemic acute renal failure, findings which may lead to improved therapy for this condition. PMID- 7779112 TI - Formation of an extremely stable polyalanine beta-sheet macromolecule. AB - We have designed a 16-mer peptide composed of a stretch of alanine residues (Ac KA14K-NH2) which is an effective, simple model for the study of beta-sheet formation in the hydrophobic cores of proteins. This peptide adopts an aqueous soluble "bundling" macromolecular beta-sheet structure, which is extremely stable to a wide range of pHs, temperatures and/or denaturants. Its unusual stability appears to be due to tight hydrophobic packing of the alanine residues in multilayer sheets or micellar forms with the multimeric lysine array being directed outward at the aqueous environment, allowing aqueous solubility. PMID- 7779114 TI - American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. AB - OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials. PMID- 7779115 TI - Joint and connective tissue ultrasonography--a rheumatologic bedside procedure? A German experience. PMID- 7779113 TI - The orphan receptor TAK1 acts as a repressor of RAR-, RXR- and T3R-mediated signaling pathways. AB - Recently, we reported the cloning and characterization of the novel orphan receptor TAK1. In this study, we analyze the interaction of TAK1 with a variety of response elements (RE's) and demonstrate that TAK1 binds effectively to RE's composed of the core motif PuGGTCA configured in direct repeats spaced by one or more nucleotides. TAK1 bound poorly to palindromic or inverted palindromic motifs and was unable to bind to a single core motif, suggesting that a dimeric site is required for binding. Transfection experiments with CV-1 cells revealed that TAK1 is able to repress retinoid- and thyroid-hormone-induced transactivation through a subset of retinoid and thyroid hormone RE's. Our studies indicate that the antagonism of RAR-mediated transactivation does not involve the formation of heterodimers between TAK1 and RAR or RXR but is due to the competition of TAK1 homodimers with RAR-RXR heterodimers and RXR homodimers for binding to RARE and RXRE, respectively. Our results suggest that the orphan receptor TAK1 can be a negative modulator of the regulation of gene expression mediated by retinoid and thyroid hormone signaling pathways. PMID- 7779116 TI - Distinct oligosaccharide content of rheumatoid arthritis-derived immune complexes. AB - OBJECTIVE: To investigate the association between glycosylation and immune complex formation in various disease groups. METHODS: Immune complexes and IgG were isolated from serum and their carbohydrate content evaluated in a dot-blot assay using specifically binding lectins. RESULTS: Significantly more N acetylglucosamine was detected in complexes from patients with rheumatoid arthritis (RA) than in those from patients with systemic lupus erythematosus, Crohn's disease, or infectious endocarditis, or from normal controls (P < 0.001). The immune complex concentration in the circulation was strongly associated with N-acetylglucosamine levels (P < 0.001 by chi-square analysis). CONCLUSION: The composition of immune complexes from RA patients is distinct in carbohydrate content from those found in other disease groups. PMID- 7779118 TI - Serum hyaluronic acid level as a predictor of disease progression in osteoarthritis of the knee. AB - OBJECTIVE: To investigate the prognostic value of serum hyaluronic acid (HA) and keratan sulfate (KS) levels in relation to tibiofemoral osteoarthritis (OA) of the knee. METHODS: Clinical and demographic data were collected on 94 patients. Radiographs were obtained at study entry and at 5-year followup. Disease progression was defined as 2 mm of joint space narrowing of any tibiofemoral compartment, and/or knee joint surgery during the study period. Serum HA and KS were measured and levels were correlated with entry data and disease progression. RESULTS: At entry, HA levels were significantly related to disease duration (P = 0.036), minimum joint space (P = 0.049), and previous surgery (P = 0.001). After these variables were taken into account, patients whose disease had progressed were shown to have had significantly higher levels of HA at baseline compared with those whose disease had not progressed (P = 0.019). However, there were no significant differences in levels of serum KS between those with and those without disease progression, at entry (P = 0.779) or at subsequent visits. CONCLUSION: These results suggest that serum HA levels predict disease outcome in OA of the knee and confirm that a single measurement of the serum level of KS is not useful as a prognostic marker in OA. PMID- 7779117 TI - Correlation between gold-induced enterocolitis and the presence of the HLA DRB1*0404 allele. AB - OBJECTIVE: In recent years we have treated 4 rheumatoid arthritis (RA) patients who developed gold-induced enterocolitis, a well-recognized, although rare, complication of chrysotherapy. The aim of the present study was to seek any genetic predisposition for this complication. METHODS: HLA DNA typing was done on fresh white blood cells from the 4 patients. RESULTS: Three of the 4 patients (75%) exhibited the DRB1*0404 allele, whereas the prevalence of this allele among the Ashkenazi Jewish population of RA patients without colitis was 9.2% and 10.2% in 2 different studies. CONCLUSION: The results indicate that the DRB1*0404 may be associated with risk for the development of gold-induced enterocolitis in this population and suggest that HLA DNA typing should be considered in Jews who may be undergoing chrysotherapy. PMID- 7779119 TI - The role of nitric oxide in lipoxin A4-induced polymorphonuclear neutrophil dependent cytotoxicity to human vascular endothelium in vitro. AB - OBJECTIVE: To assess the mechanism for the cytotoxicity of human polymorphonuclear neutrophils (PMN) to human umbilical vein endothelial cells (HUVEC) induced by the 5- and 15-lipoxygenase product of arachidonate, lipoxin A4 (LXA4), and the phorbol ester, phorbol myristate acetate (PMA). METHODS: HUVEC were grown to confluence and labeled with 51Cr. PMN and stimuli were added, and the release of 51Cr into supernatants was assessed after 4 hours. RESULTS: Both LXA4 and PMA conferred highly significant PMN-dependent cytolysis. The cytotoxicity activated by LXA4 was inhibited by NG-monomethyl-L-arginine (L-NMA) and by nitro-L-arginine methyl ester, specific inhibitors of the nitric oxide (NO)-producing enzyme NO synthase. Also, the scavenger of extracellular NO, oxyhemoglobin (HbO2), prevented LXA4-induced cytolysis in a dose-dependent manner. In sharp contrast, L-NMA did not significantly affect the cytolysis induced by PMA, whereas HbO2 showed a modest inhibitory action. In experiments without PMN, addition of the NO donor S-nitroso-N-acetyl-penicillamine to HUVEC induced marked cytolysis, which was inhibited by HbO2, but not by L-NMA. Addition of L-arginine or arginine analogs did not affect superoxide anion production in a cell-free hypoxanthine/xanthine oxidase system. Both LXA4 and PMA induced the production of superoxide anion from PMN and of NO from HUVEC: CONCLUSION: NO produced by HUVEC, interacting with PMN which produce superoxide anions, is of marked significance for the endothelial cell damage in this in vitro model of vasculitis. This is probably due to the subsequent formation, via a radical radical interaction between NO and .O2-, of cytotoxic products, such as peroxynitrite and its metabolites. Furthermore, although LXA4 and PMA induced comparable cytolysis at optimal concentrations, the relative importance of NO compared with other mechanisms mediating cytotoxicity was stimulus dependent, and NO was relatively more important for LXA4-induced PMN-dependent endothelial injury. PMID- 7779120 TI - Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus. AB - OBJECTIVE: To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. METHODS: Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution. RESULTS: Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. CONCLUSION: Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs. PMID- 7779121 TI - Finger tendon involvement in rheumatoid arthritis. Evaluation with high-frequency sonography. AB - OBJECTIVE: To characterize finger tendon involvement in patients with rheumatoid arthritis (RA). METHODS: The finger tendons of 20 RA patients were studied by ultrasonography using a high-frequency (13-MHz) transducer. RESULTS: Eighteen patients (90%) showed finger tendon abnormalities: widening of the flexor tendon sheath (80%), loss of the normal fibrillar echotexture (60%), irregularity of the extensor (30%) and flexor (50%) tendon margins, tendon tear (10%), synovial cyst (20%). CONCLUSION: High-frequency sonography is helpful in assessing even minimal finger tendon lesions in RA patients. PMID- 7779122 TI - A self-administered rheumatoid arthritis disease activity index (RADAI) for epidemiologic research. Psychometric properties and correlation with parameters of disease activity. AB - OBJECTIVE: To examine the psychometric properties and construct validity of a self-administered Rheumatoid Arthritis Disease Activity Index (RADAI). METHODS: Five items of the Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire were aggregated into the RADAI and assessed for their factor loading, internal consistency, and construct validity. RESULTS: In 55 patients with RA, the RADAI had a high internal consistency (Cronbach's alpha = 0.91) and correlated with physician's assessment of disease activity (r = 0.54, P < 0.01), the swollen joint count (r = 0.54, P < 0.01), and the C-reactive protein value (r = 0.43, P < 0.01). CONCLUSION: The RADAI is a highly reliable and valid self administered measure of disease activity for clinical, health services, and epidemiologic research. Its sensitivity to change in longitudinal studies needs further study. PMID- 7779123 TI - Cardiovascular fitness and health in patients with end-stage osteoarthritis. AB - OBJECTIVE: To evaluate the cardiovascular fitness of a group of patients with severe osteoarthritis (OA). METHODS: Thirty-seven patients with end-stage OA were evaluated just before hip or knee replacement surgery. Severity of arthritis was evaluated using standardized techniques. Patients and age- and sex-matched controls underwent a single, maximal, symptom-limited, cardiopulmonary exercise test using arm or leg ergometry and a metabolic cart to measure expired respiratory gases. RESULTS: Severe musculoskeletal disability and deformity was confirmed in the OA patient group. During exercise testing, OA patients were able to perform physiologically maximal cardiopulmonary exercise. Arthritis patients were noted to be severely deconditioned, with reduced peak oxygen consumption (OA hips mean +/- SD 14.9 +/- 4.2 versus control hips 19.0 +/- 4.6, P < 0.0001; OA knees 12.8 +/- 3.7 versus control knees 17.6 +/- 5.2 ml/kg/minute, P < 0.0005). A trend for more frequent manifestations of coronary heart disease in OA patients than in controls (27% versus 13%; P > 0.05) was also noted. CONCLUSION: Patients with end-stage lower extremity OA are severely deconditioned. This may place them at incremental risk for the development of coronary heart disease. PMID- 7779124 TI - Osteoporosis in rheumatoid arthritis. A monozygotic co-twin control study. AB - OBJECTIVE: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study. RESULTS: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites. CONCLUSION: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease. PMID- 7779125 TI - Spin-spin relaxation of brain tissues in systemic lupus erythematosus. A method for increasing the sensitivity of magnetic resonance imaging for neuropsychiatric lupus. AB - OBJECTIVE: To correlate the spin-spin relaxation time (T2) of brain tissue in neuropsychiatric systemic lupus erythematosus (NPSLE) with the patient's clinical condition. METHODS: T2 values were determined in 54 SLE patients and 45 non-SLE controls at 1.5 Tesla, using intensity from multi-echo magnetic resonance (MR) images fitted to an exponential decay curve with rate-constant T2. RESULTS: The T2 of white matter was increased in SLE patients compared with controls (P = 0.01) and was increased in those patients who had previously experienced major NPSLE: Patients with acute diffuse neurologic manifestations (seizures, psychosis, coma) demonstrated a longer T2 of the gray matter (mean +/- SD 92.75 +/- 6.35 ms, n = 10) than did other SLE patients (mean +/- SD 79.61 +/- 5.04 ms, n = 44) (P = 0.02 by t-test), which suggests acute cerebral edema. The mean T2 values of reversible and nonreversible focal lesions were significantly different (P < 0.02), indicating different microenvironments and micropathology. CONCLUSION: Quantitative T2 measurement extends the utility and sensitivity of conventional MR imaging for evaluating NPSLE: PMID- 7779127 TI - The contributions of disease activity, sleep patterns, and depression to fatigue in systemic lupus erythematosus. A proposed model. AB - OBJECTIVE: This study describes lupus fatigue multidimensionally and introduces a multivariate model: Sleep problems and depression, through reciprocal effects on each other, act as mediators through which lupus disease activity increases fatigue. METHODS: Self-reported sleep patterns, depression, and fatigue were assessed in 48 women with systemic lupus erythematosus (SLE) and 27 women from the general population. Rheumatologists rated current lupus disease activity. RESULTS: The SLE group reported greater overall fatigue than did the controls. Temporal and affective dimensions of fatigue were more differentiating than sensory or severity dimensions. The SLE group also reported longer sleep latency and total sleep time, but not higher depression. Using 2-stage regression, a form of structural equation modeling, the proposed lupus fatigue model was supported. CONCLUSION: These preliminary results describe fatigue as a multidimensional phenomenon arising out of several contributing factors. They suggest that fatigue treatment strategies should address mediating processes such as sleep and depression, in addition to disease activity. PMID- 7779128 TI - The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis. AB - OBJECTIVE: To determine which early clinical data differentiate juvenile-onset ankylosing spondylitis (AS) from juvenile rheumatoid arthritis (JRA). METHODS: Medical records of 35 patients with juvenile-onset AS and 75 with JRA (excluding type II pauciarticular JRA), all of whom had disease onset at age < or = 16 years, disease duration of < or = 2 1/2 years at the initial visit to the rheumatology clinic, and followup of > or = 10 years, were analyzed retrospectively with regard to features of disease found 6 months, 12 months, and 10 years after onset. RESULTS: At 6 months, various features appeared more frequently in the juvenile-onset AS group than in the JRA group, i.e., pauciarthritis (54.3% versus 30.7%; P = 0.03, odds ratio [OR] = 2.7), enthesopathy (82.9% versus 0%; P < 0.0001, OR = 321.4), tarsal disease (71.4% versus 1.3%; P < 0.0001, OR = 185.0), and lumbar/sacroiliac symptoms (11.4% versus 0%; P = 0.02, OR = 11.9). At 12 months, the features found more frequently among juvenile-onset AS patients than JRA patients were enthesopathy (88.6% versus 4.0%; P < 0.0001, OR = 186.0), tarsal disease (85.7% versus 10.7%; P < 0.0001, OR = 50.3), and knee disease (100.0% versus 82.7%; P = 0.04, OR = 8.0). Involvement of the upper extremities (especially the hands) was found in significantly fewer juvenile-onset AS patients compared with the JRA group. Definite involvement of the spine and sacroiliitis in juvenile-onset AS occurred after a mean +/- SD of 7.3 +/- 2.0 years. CONCLUSION: Regardless of axial disease, enthesopathy and tarsal disease in children who have arthritis of the lower, but not of the upper extremities differentiate juvenile-onset AS from JRA within 1 year of symptoms. The discriminative value of these parameters approaches that of axial disease (the gold standard) throughout the followup period. PMID- 7779126 TI - Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. AB - OBJECTIVE: To measure the anatomic and physiologic changes in the synovium of patients with active rheumatoid arthritis (RA) before and after the initiation of treatment with low-dose systemic glucocorticoids and methotrexate (MTX). METHODS: Two patients with RA with active synovitis involving the carpus were evaluated by imaging parameters at baseline and again after 14 weeks (of treatment with low dose prednisone and MTX). Standard clinical parameters, laboratory measurements, and contrast-enhanced magnetic resonance imaging (MRI) (synovial volume estimate) and positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (18-FDG) (synovial metabolism estimate) were performed. RESULTS: Compared with baseline, standard clinical parameters (i.e., joint count, joint index, morning stiffness, global assessments of arthritis activity, and erythrocyte sedimentation rate) improved dramatically in both patients after treatment with low-dose prednisone and MTX. In concert with this trend, the synovial volume of the affected wrist was reduced by 60%, and 76% and the metabolism of 18-FDG was reduced by 66% and 69% in the 2 patients. CONCLUSION: These preliminary observations indicate that a volumetric estimate of inflamed synovium (using contrast-enhanced MRI) and quantification of synovial deoxyglucose metabolism (using PET) are technically feasible and, in the 2 reported cases, correlate well with standard outcome measures. These imaging modalities may provide new objective parameters to determine RA disease activity and effectiveness of antirheumatic medications; however, the potential clinical utility of these measures remains to be defined. PMID- 7779129 TI - The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Multivariate relative risk model. AB - OBJECTIVE: To identify HLA markers for the development of severe disease in psoriatic arthritis (PsA). METHODS: Patients with PsA who were followed up prospectively over a 14-year period were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6 month intervals according to a standard protocol, which also included serologic HLA typing for class I and II antigens. Progression of damage was defined as transition into higher damage states, defined by the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. RESULTS: Univariate analysis revealed that the HLA antigens B27, B39, and DQw3 were associated with disease progression, while HLA DR7 was "protective." The best multivariate model identified the HLA antigens B27, when DR7 was present, and DQw3, when DR7 was not present, as predicting disease progression across all transitions, while HLA-B39 was associated with progression in early disease. The addition of these HLA indicators to a model containing clinical variables resulted in a significant improvement in fit. CONCLUSION: The HLA antigens associated with PsA, B27 and B39, are risk factors for disease progression, as is the HLA class II antigen DQw3. In combination with clinical measures of disease, these HLA variables are the dominant predictors of progression. PMID- 7779130 TI - Comparative prospective, double-blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget's disease of bone. AB - OBJECTIVE: To compare the efficacy and safety of tiludronate and etidronate at the same dosage (400 mg/day) for the treatment of active Paget's disease of bone. METHODS: We studied 234 patients with radiologic lesions characteristic of Paget's disease of bone and serum alkaline phosphatase (AP) concentrations at least twice the upper limit of normal, in a prospective, randomized, double blind, multicenter clinical trial lasting 6 months. Patients were randomly allocated into 1 of 3 treatment groups: tiludronate for 3 months followed by placebo for 3 months, tiludronate for 6 months, or etidronate for 6 months. Serum AP levels and urinary hydroxyproline excretion were measured at baseline and after 3 months and 6 months. Patients with a reduction of at least 50% in the serum AP concentration were considered to be responders. RESULTS: After 3 months, the proportion of responders was higher in the tiludronate group (57.4%) than in the etidronate group (13.9%) (P < 0.0001). In the etidronate group, this percentage was lower among patients who had received previous treatment with a bisphosphonate (2.3%) than among those who had not (28.6%) (P < 0.01). Previous bisphosphonate treatment was not associated with response in the tiludronate group. After 6 months, the proportion of responders did not differ between the 2 tiludronate groups (60.3% and 70.1%), but was lower in the etidronate group (25.3%) (P < 0.0001). There was a higher proportion of patients with treatment resistant disease (< 25% reduction of serum AP) in the etidronate group (51.9%) than in the tiludronate 3-month group (17.9%) or the tiludronate 6-month group (19.5%) (P < 0.0001). Gastrointestinal disturbances were more common, and occurred earlier, with tiludronate, but they were mostly mild, requiring no treatment. CONCLUSION: Tiludronate at 400 mg/day for 3 months or 6 months is more effective than the same dosage of etidronate for 6 months in the treatment of Paget's disease. PMID- 7779132 TI - Gottron's papules? Acanthosis nigricans. PMID- 7779131 TI - Diagnostic use of office-based ultrasound. Baker's cyst of the right knee joint. PMID- 7779133 TI - Epstein-Barr virus-associated Hodgkin's lymphoma in a rheumatoid arthritis patient treated with methotrexate and cyclosporin A. PMID- 7779135 TI - Fibromyalgia prevalence in patients with systemic lupus erythematosus: comment on the article by Middleton et al. PMID- 7779134 TI - On focal lymphocytic sialadenitis as a gold standard for the diagnosis of Sjogren's syndrome: comment on the article by Daniels and Whitcher. PMID- 7779136 TI - Prevalence of fibromyalgia in systemic lupus erythematosus patients: comment on the article by Middleton et al. PMID- 7779137 TI - Western blot analysis by image processing: comment on the article by Kowal and Weinstein. PMID- 7779138 TI - Use of genetic typing versus other markers for predicting outcome in patients with inflammatory arthritis: comment on the article by Gough et al. PMID- 7779139 TI - Improved methotrexate patient information. PMID- 7779140 TI - Aliphatic and heterocyclic analogues of arecaidine propargyl ester. Structure activity relationships of mono- and bivalent ligands at muscarinic M1 (M4), M2 and M3 receptor subtypes. AB - The pharmacological profiles of tertiary and quaternary monovalent (1b-6b) and bivalent ligands (7a-12b), closely related to arecaidine propargyl ester (CAS 35516-99-5, APE, 1a), were evaluated at muscarinic receptors in rat superior cervical ganglia (M1), rabbit was deferens (M1/M4-like), guinea-pig atria (M2) and guinea-pig ileum (M3). In the monovalent ligand series (1a-6b) APE (1a) displayed the highest potency at all three muscarinic receptors [M2 (-log EC50 = 8.12) > or = M3 (-log EC50 = 7.77) = M1/M4 (-log EC50/vas deferens = 7.72)], whereas in the bivalent ligand series (7a-12b) arecaidine 2-butyne-1,4-diyl bisester (bisABE, 7a) was the most potent agonist with functional selectivity for M1/M4 (-log EC50/vas deferens = 6.94) and M2 receptors (-log EC50 = 7.10) over M3 receptors (-log EC50 = 6.27). On ganglia bisABE elicited M2 receptor-mediated hyperpolarisations, which were followed by long-lasting pirenzepine-sensitive depolarisations. However, the potency at M1 receptors in ganglia of APE (-log EC50 = 6.96) and bisABE (-log EC50 = 5.69) was lower than that in rabbit vas deferens. All bivalent molecules exhibited decreased potencies when compared with their monovalent analogues. However, a change in potency profiles was often obtained. The quaternary isonicotinic acid 2-butyne-1,4-diyl bisester (10b) displayed some functional selectivity for M2 receptors (-log EC50 = 5.78) [6- to 9-fold over M1/M4 (-log EC50/vas deferens = 5.03) and M3 receptors (-log EC50 = 4.83)] without showing nicotinic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779141 TI - General pharmacology of the putative cognition enhancer linopirdine. AB - The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1 phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses. PMID- 7779142 TI - Steady-state pharmacokinetics of nimodipine during chronic administration of indometacin in elderly healthy volunteers. AB - The possible influence of chronic indometacin (CAS 53-86-1) medication on nimodipine (CAS 66085-59-4) pharmacokinetics was investigated in 24 elderly healthy subjects. Both drugs were orally administered in a non-blinded, randomized, twofold crossover design. The study periods with a 5-day treatment each were separated by a 2-week washout period. The Css,max of nimodipine was increased after the combined administration of nimodipine (30 mg t.i.d.) and indometacin (25 mg b.i.d.) as compared with those after nimodipine monotherapy: 24.2 +/- 14.7 micrograms/l vs. 19.7 +/- 10.3 micrograms/l. This increase, however, was not of an order to become clinically relevant. Nimodipine AUCss slightly increased under indometacin co-medication from 57.9 +/- 27.5 micrograms.h.l-1 to 62.8 +/- 26.6 micrograms.h.l-1, resulting in a mean relative bioavailability of nimodipine of 111% with a 90%-confidence interval of 96-128% for the combined medication. There was no evidence of any clinically relevant difference in hemodynamics and other findings between both treatments. The overall frequency of side effects was low after both medication regimens. The findings of this study indicate that a combined treatment with both compounds should not be associated with a clinically relevant interaction. PMID- 7779143 TI - [Effects of intravenous anaesthetics on excitation, conduction, and refractory parameters of the heart. Experimental study in the dog]. AB - Cardiac excitation, conduction, and refractory parameters of the heart were investigated in 59 beagle dogs to obtain basic values under the influence of the following 11 intravenous anaesthetic regimes using HIS-bundle electrography and programmed stimulation: 1. Alfentanil/midazolam/succinylcholine; 2. alfentanil/midazolam/succinylcholine/atropine; 3. fentanyl/midazolam/pancuronium bromide; 4. fentanyl-droperidol/chloralose/urethane; 5. ketamine/xylazine; 6. ketamine/xylazine/atropine; 7. propionylpromazine/pentobarbital; 8. propionylpromazine/levomethadon; 9. propofol; 10. propofol/alfentanil; 11. Tiletamine-zolazepam. It could be shown, that some intravenous anaesthetics under laboratory conditions have a strong influence on the observed cardiac parameters that must be considered in experiments with other substances or in cardiovascular results. PMID- 7779144 TI - Mechanisms of the potent and long-lasting antihypertensive action of the new calcium channel blocker pranidipine. Evidence for strong affinity to the calcium channels or membranes. AB - To elucidate the mechanisms of the potent and long-lasting antihypertensive action of pranidipine (CAS 99522-79-9, OPC-13340), a wash-out experiment in isolated rat aorta preparations and a displacement binding experiment of (+)[3H]PN200-110 (isradipine) with pranidipine and other dihydropyridines to porcine skeletal T-tubules was conducted. It was revealed that the inhibition of KCl-induced contraction by pranidipine remained complete even after washing out the drug 9 times. Also, pranidipine had the lowest Ki value for (+)[3H]PN200-110 binding in skeletal T-tubules. The lipophilicity of pranidipine measured by octanol-buffer partition coefficient was the highest among the tested compounds, and the order of lipophilicity coincided with the order of potency in the displacement binding experiments. These results suggest that pranidipine has a very high affinity to Ca channels or to T-tubule membranes, and strongly support the "membrane-bilayer pathway hypothesis" which assumes the partitioning of the drug into the lipid bilayer before drug binding to Ca channels as an explanation of the potent and long-lasting action of pranidipine compared with other dihydropyridines. PMID- 7779145 TI - Protection of myocardial tissue against deleterious effects of oxygen free radicals by ceruloplasmin. AB - This study describes the carioprotective effect of ceruloplasmin (CAS 9031-37-2) against oxygen free radical injury, as indicated by several biochemical indicators and some cardiodynamic variables. Isolated rat hearts (n = 4-8, p < 0.05, for each experimental point) in Langendorff preparation were exposed to oxygen free radicals generated by electrolysis (10 mA) in the absence and the presence of 0.25 mumol/l purified ceruloplasmin and denaturated ceruloplasmin, in Krebs-Henseleit perfusion solutions. Biochemical indicators (noradrenaline, malondialdehyde, creatine-kinase, lactate dehydrogenase, aspartate aminotransferase, Ca2+ and Mg2+) as well as the electrocardiogram and the left ventricular pressure (LVP), were altered by oxygen free radicals formation, denoting major cellular and tissular damages in the nontreated hearts. Ceruloplasmin exhibited a cardioprotective effect and prevented the oxygen free radical-induced release of noradrenaline, indicating that it can also protect the sympathetic nerve endings from oxygen free-radical injury. Purified ceruloplasmin, a circulating extracellular antioxidant and oxygen free radical scavenger, seems to be an effective heart protective agent against myocardial and neuronal injuries generated by oxygen free radicals. PMID- 7779146 TI - Effects of the natural flavonoid delphinidin on diabetic microangiopathy. AB - The purpose of the present study was to investigate the effects of the flavonoid delphinidin chloride (CAS 528-53-0, IdB 1056) on diabetic microangiopathy. Hamsters were injected with alloxan and cheek pouch microcirculation was observed by a fluorescent microscopy technique 90 days from alloxan. The increase in permeability, the number of adhering leukocytes to venular vessel wall and vasodilatory responses to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. In diabetic group microvascular permeability and the number of sticking leukocytes to the venular endothelium were increased. Vasoconstriction by Ach was observed while the vasodilation by SNP was significantly attenuated in diabetic animals. These results are consistent for a decreased relaxation and suggest also an impairment in the smooth muscle cell function in diabetic arterioles. IdB 1056 exhibited an inhibitory effect on increased microvascular permeability and on leukocytes adhering to the venular vessels. Indeed, the treatment with IdB 1056 in diabetic hamsters pretreated or not with indometacin, a cyclooxygenase inhibitor, restored the relaxant responses to Ach and SNP. In conclusion, the effects of IdB 1056 observed in vivo at the microcirculatory level prevent the injury to endothelial cell function associated with diabetes and/or oxidative stress. PMID- 7779147 TI - Studies on the in vitro and in vivo genotoxicity of [2,2-dimethyl-6- (4 chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid. AB - [2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl] acetic acid (CAS 156897-06-2, ML 3000) was examined for genotoxic activity in bacteria and mammalian cells in vitro as well as in vivo. The substance did not increase gene mutation frequencies either in a bacterial system or in a cultured V79 cell line of the Chinese hamster. Both in vitro tests were conducted in the presence and absence of S9-mix. In the unscheduled DNA synthesis assay in vitro with primary rat hepatocytes, negative results were also obtained. A cytogenetic analysis of the bone marrow of male and female Wistar rats was performed. After oral application ML 3000 did not increase the number of cells with structural chromosomal aberrations. The results suggest that ML 3000 has no genotoxic potential in vitro and in vivo. PMID- 7779148 TI - Gastrointestinal blood loss induced by three different non-steroidal anti inflammatory drugs. AB - A clinical study was performed on 18 healthy volunteers to compare the gastrointestinal daily blood loss induced by oral intake of three different non steroidal anti-inflammatory drugs, lysine clonixinate (CAS 55837-30-4), ibuprofen (CAS 15687-27-1) and acetylsalicylic acid (CAS 50-78-2 ASA). For quantitative determination of gastrointestinal blood loss, autologous erythrocytes were radiolabelled in vitro with 51Cr and reinfused at study start. The amount of radioactivity excreted in faeces was measured during a placebo baseline phase of three days, a treatment phase of five days with thrice daily dosing of ASA, ibuprofen or lysine clonixinate and a subsequent wash-out phase of five days. The highest increase of mean daily blood loss over baseline was observed after treatment with ASA (+ 1.66 ml/d versus baseline). Treatment with ibuprofen led to an increase of mean daily blood loss by + 0.52 ml/d. During treatment with lysine clonixinate the mean increase of daily blood loss was +0.32 ml/d versus baseline. In the ibuprofen and lysine clonixinate treatment groups the values of mean daily blood loss decreased during the wash-out phase with respect to the verum phase, whereas the mean daily blood loss during the wash-out phase after treatment with ASA even increased in comparison to the verum phase (mean daily blood loss: +2.07 ml/d versus baseline. PMID- 7779150 TI - [Symptomatic therapy with famotidine in non-erosive gastro-esophageal reflux. Results of an open multicenter study]. AB - 180 patients suffering from frequent heartburn and endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis entered an open, multicentre study to evaluate the 6-week safety profile and efficacy on symptom relief of famotidine (CAS 76824-35-6, Pepdul mite), a potent and long-acting H2-receptor antagonist. By week 6 the cumulative percentage of patients with defined response, that is complete relief of heartburn in 5 days and only mild discomfort in the remaining 2 days of a week, reached 68.9%, whereas the cumulative percentage of patients with complete relief of heartburn within a week reached 52.7%. Throughout the evaluation period famotidine relieved nighttime heartburn better than daytime heartburn. More than 75% of the responders remained without recurrence. Even the non-responders experienced a 60-70% reduction of heartburn severity assessed using scores. Antacid consumption was reduced from 18 tablets (median) in week 0 to 5 tablets in week 6. 90% of the patients reported at week 6 excellent (67.2%) or moderate (22.8%) symptomatic improvement. No serious adverse events attributable to famotidine occurred. It is concluded that in patients with non-erosive gastro-oesophageal reflux disease famotidine therapy, 20 mg twice daily, is highly effective in reducing reflux disease symptoms. PMID- 7779149 TI - Study on the possible interaction between tenoxicam and atenolol in hypertensive patients. AB - Sixteen hypertensive male out-patients (33-54 y), whose blood pressure (BP) had been normalized (diastolic BP < 90 mmHg) by treatment with a daily dose of 50 mg atenolol (CAS 29122-68-7), participated in this double-blind, placebo-controlled, parallel group study, which investigated the possible influence of the non steroidal anti-inflammatory drug tenoxicam (CAS 59804-37-4) on the control of BP by atenolol. After a run-in of 10 days, to assess the stability of BP control by atenolol, and to determine baseline parameters, 8 patients in group A received 20 mg tenoxicam (2 x 20 mg on days 1 and 2), and 8 patients in group B received placebo, daily over 15 days (days 0-14), concomitantly with their atenolol regimen. BP was measured under standardized conditions on several days. Heart rate (EHR) after 5 min of exercise by bicycle ergometry (constant 75W), and parameters of renal function were assessed before (baseline) and during concomitant dosing of atenolol and tenoxicam. On day 14 the mean changes (delta A, delta B) from baseline of pre-dose BP (mmHg) and EHR (beats/min) in groups A and B, and the one-sided 95% confidence regions (R) for delta A, respectively, were (delta A, delta B, R): 4.4, 1.6, < 9.5 for sitting systolic BP, 2.8, -0.3, < 4.5 for sitting diastolic BP, -0.3, -0.6, < 5.5 for standing systolic BP, -0.6, 1.9, < 3.0 for standing diastolic BP, 0.4, -7.5, < 0.4 for EHR at pre-dose, 3.1, 0.6, < 7.8 for EHR at 3.5 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779152 TI - Pharmacokinetics and bioavailability of different formulations of aciclovir. AB - The pharmacokinetics and bioavailability of aciclovir (CAS 59277-89-3) were examined after administration of newly developed 200 mg and 400 mg tablets. Two studies, each with 24 subjects of either sex, were performed. In the three-way study I, two different tablets containing 200 mg of aciclovir (test and reference products) and a short infusion of 250 mg aciclovir were compared. In the two-way study II, the bioequivalence of a newly developed 400 mg aciclovir tablet was tested against a standard product. Irrespective of dose, the peak plasma aciclovir levels were obtained 1.5 h after administration of the tablets. In the case of the 200 mg tablets, the mean Cmax-values were 454 ng/ml (pilot test formulation, T) and 525 ng/ml (reference formulation, R), whereas the mean Cmax values after administration of the 400 mg tablets were 779 (T) and 800 (R) ng/ml for test and reference formulation, respectively. The mean AUC calculated to the time of the last measurement in each instance was in the order of 2290 (T) and 2275 (R) ng/ml x h (200 mg tablets) or 3726 (T) and 3855 (R) ng/ml x h (400 mg tablets). The amount of the dose renally excreted as unchanged aciclovir was measured at 20.8 (T) - 21.8 (R)% with the 200 mg tablets and 14.3 (T) - 15.1% (R) with the 400 mg tablets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779151 TI - [Immunoactive effects of various mistletoe lectin-1 dosages in mammary carcinoma patients]. AB - Cellular aspects of the immunomodulating activity of a proprietary mistletoe extract (Eurixor) standardized for mistletoe lectin-1 (ML-1) were investigated in patients suffering from mammary carcinoma (n = 20). Regular subcutaneous injections of the different dosages (0.5 and 1.0 ng ML-1/kg body weight, twice a week, for 5 weeks) yielded statistically significant increases of defined peripheral blood lymphocyte subsets (helper T-cells, natural killer (NK)-cells) which are generally believed to be involved in antitumor activity. Moreover, administration of either ML-1 concentration resulted in enhanced expression of activation markers such as interleukin-2 receptors and HLA/DR-antigens on peripheral blood T-lymphocytes. This study suggests that regular subcutaneous administration of both ML-1 concentrations (0.5 and 1.0 ng/kg body weight) can efficiently stimulate the cellular immune system of cancer patients. PMID- 7779154 TI - Efficacy of a combination of metrifonate and praziquantel in the treatment of Schistosoma mansoni infection in albino mice. AB - This study aimed to test the therapeutic effect of two antischistosomal drugs metrifonate (CAS 52-68-6) and praziquantel (CAS 55268-74-1), either alone or in combination, on mice infected with schistosoma mansoni. Both drugs were given in half of their therapeutic doses 8 weeks post infection. Animals were sacrificed two weeks after the last dose. The efficacy of the drugs was evaluated using the number of ova/g tissue, the distribution and the number of Schistosoma worms. Praziquantel and metrifonate alone produced about 91% and 22% reduction in total worm burden. The reduction in ova count in intestine and liver was 96% and 85%, respectively, using praziquantel alone while it was only 6 and 12%, respectively, after metrifonate treatment. After treatment with both drugs given in combination the number of ova count was not changed as compared with praziquantel alone; also there was no change in the worm load as compared with praziquantel. It is concluded that a combination of a low dose of praziquantel with metrifonate failed to produce any significantly better effect. PMID- 7779153 TI - Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel. AB - The effects of cimetidine, bicarbonate and glucose on the bioavailability of the two brands of praziquantel (CAS 55268-74-1) available in Egypt were studied in normal healthy volunteers. Brand 1 when coadministered with cimetidine showed elevated concentration of the drug at all time intervals. The difference was statistically significant at 3, 4, 6 and 8 h following treatment. On the other hand coadministration of cimetidine with brand 2 (Distocide) showed elevated concentration of the drug 1 h post treatment. Analysis of the pharmacokinetic parameters revealed insignificant difference comparing brand 1 versus brand 1 plus cimetidine. Significant differences were observed between the elimination rate constant Ke (h-1) for brand 2 (0.017 +/- 0.004) alone versus brand 2 plus cimetidine (0.006 +/- 0.001). Coadministration of bicarbonate or glucose with either brand 2 or brand 1 tended to depress the serum concentration of praziquantel. Possible explanations of these findings are discussed. PMID- 7779157 TI - Families facing choices. PMID- 7779155 TI - Immunogenicity of biosynthetic human LysPro insulin compared to native-sequence human and purified porcine insulins in rhesus monkeys immunized over a 6-week period. AB - Development of insulin antibodies in rhesus monkeys was investigated after immunization with 3 forms of insulin in Freund's adjuvant. Insulins examined included: 1. biosynthetic LysPro insulin (LY275585), a new human insulin analog, 2. biosynthetic native-sequence human insulin, and 3. purified porcine insulin. Male monkeys, 4/insulin type, were immunized weekly over a 6-week period with increasing doses of insulin, ranging from 10 to 100 micrograms/monkey. An ELISA assay was used to measure IgG insulin antibodies in sera collected prior to immunization and 5, 10, and 16 days after final immunization. One monkey had detectable pretreatment levels of antibody. This monkey, which had been assigned to the LysPro insulin treatment group, responded to immunization with a peak antibody level of 20 micrograms/ml. IgG insulin antibody responses were not detected in any of the other monkeys. A passive cutaneous anaphylaxis (PCA) assay was used to measure IgE insulin antibodies in sera collected prior to immunization and 10 days after final immunization. No IgE antibodies were detected in any of the monkeys pre- or post-immunization. Considering that 1. an immunological adjuvant was used, 2. eleven of twelve monkeys failed to develop an antibody response, and 3. the IgG insulin antibody level observed in the single responding monkey was low, it was concluded that these insulins have an extremely weak immunogenic potential in rhesus monkeys. It is suggested that immunization of non-human primates with new therapeutic proteins in adjuvant may be a useful primary screen to determine their immunogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779158 TI - Showing sensitivity to deaf culture. PMID- 7779156 TI - Seize the day. PMID- 7779159 TI - The challenge of literacy. PMID- 7779160 TI - Where are dysphagia courses? PMID- 7779161 TI - AuD should do more. PMID- 7779162 TI - Look who's laughing. PMID- 7779163 TI - [New clinical tests in diagnosis of collagen diseases and allergic diseases]. PMID- 7779164 TI - Activin enhances osteoclast-like cell formation in vitro. AB - The effect of activin (activin A/EDF) on osteoclast formation was investigated. In mouse bone marrow cell cultures, activin enhanced the formation of tartrate resistant acid phosphatase (TRACP)-positive multinucleated cells (MNC) in a dose dependent manner, either in the presence or absence of 1,25-(OH)2D3 or PTH. In organ cultures of neonatal mouse calvaria, activin also enhanced the generation of TRACP-positive giant cells in the endosteal periosteum and increased the TRACP staining of whole calvaria, but did not exhibit bone resorbing activity. These results indicate that activin stimulates the formation of osteoclasts, but not osteoclast activation. Activin is produced by bone marrow cells and might be involved in the local process of osteoclast differentiation. PMID- 7779165 TI - Involvement of adhesion molecules LFA-1 and ICAM-1 in osteoclast development. AB - We report here that leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) are involved in osteoclast development. Osteoclast development was observed on co-culture of mouse spleen cells and mouse bone marrow derived clonal stromal cells, TMS-14, in the presence of 1 alpha, 25-dihydroxyvitamin D-3 (1 alpha, 25-(OH)2D3) for 8 days, and quantified with respect to tartrate-resistant acid phosphatase (TRACP) activity. When either one of the monoclonal antibodies (MAbs) to mouse LFA-1 and mouse ICAM 1 was added to the co-culture system, the TRACP activity was significantly inhibited. The experiment in which one-day treatment with each of these MAbs was performed during the 8 days of cultivation showed that the inhibitory effects of both MAbs on the TRACP activity at 8 days were observed from an early stage of the culture, but were more notable at a later stage (days 4-6). As the expression of ICAM-1 was observed on both spleen cells and TMS-14, we next examined whether the interaction between stromal cells and osteoclast progenitors or among osteoclast progenitors was more important for osteoclast development. To determine this, rat spleen cells and a MAb to rat ICAM-1 were used instead of those of mouse. When MAb to rat ICAM-1 or mouse ICAM-1 was added to the co culture system of rat spleen cells and TMS-14, the inhibitory effect of the MAb to rat ICAM-1 was mainly observed at a later stage of the culture period and that of anti-mouse ICAM-1 antibody was only observed at an earlier stage. These results indicate that adhesion molecules LFA-1 and ICAM-1 may play a role in osteoclast development via interaction between stromal cells and osteoclast progenitors as well as among osteoclast progenitors. PMID- 7779166 TI - [Does no Helicobacter pylori mean no duodenal ulcer?]. PMID- 7779167 TI - Beyond Moore: issues of law and policy impacting human cell and genetic research in the age of biotechnology. PMID- 7779168 TI - [Assessment of selective intestinal permeability using a novel, simple carbohydrate absorption test]. PMID- 7779169 TI - [Large differences in phototherapy policy for neonatal jaundice in Dutch centers]. PMID- 7779170 TI - [Ointments or tweezers?]. PMID- 7779171 TI - [Leukemia, cytostatic therapy and pregnancy]. PMID- 7779172 TI - [Infant nutrition]. PMID- 7779173 TI - [Annual test for occult blood in stool and intestinal cancer mortality]. PMID- 7779174 TI - [Bovine heterologous bone graft in orbital surgery]. AB - Lubboc (T650) is a bovine heterologous bone implant obtained by specific preparation of trabecular of bone. In vitro and in vivo biocompatibility studies have revealed the absence of any cytotoxicity or systemic toxicity. Lubboc has many fields of application, including all bone graft surgical indications. We report our first results concerning the use of this product in orbital surgery either as a filling or contention material or as an apposition material. On all 20 operated patients we did not encounter any intolerance, inflammation or infection. The follow-up is still too short to appreciate the long term integration of this material which has the advantage of being a substitute for autologous bone, avoiding bone graft harvesting. PMID- 7779175 TI - Access to specialty care. PMID- 7779176 TI - A B-cell coactivator of octamer-binding transcription factors. AB - The octamer motif (ATGCAAAT) paradoxically plays a central role in mediating the activity of both B-cell specific and ubiquitous promoters. It has been widely assumed that the predominantly lymphoid-restricted octamer-binding factor Oct-2 mediates tissue-specific promoter activity, whereas the ubiquitously expressed Oct-1 mediates general promoter activity, but this view has been challenged. Here we use a modified yeast one-hybrid assay to isolate a B-cell factor, Bob1, which associates with either Oct-2 or Oct-1. In transfection experiments, this factor boosts Oct-1-mediated promoter activity and to a lesser extent, that of Oct-2. This coactivation is strictly dependent on the specific interaction with Oct-1 or Oct-2 because deletion of the octamer motif abolishes coactivation. We conclude that Bob1 could represent a new tissue-specific transcriptional coactivator which may convert a ubiquitously expressed transcription factor to a cell-type-specific activator. PMID- 7779177 TI - Isolation and studies of the mutagenic activity of saponins in the Ames test. AB - Mutagenic activity of medicagenic acid, medicagenic acid 3-0-glucopyranoside and soyasaponin I was tested by the Ames method with S. typhimurium strains TA97, TA98, TA100, TA102 in the absence and the presence of metabolic activation (S9 mix). These saponins have been isolated and identified from alfalfa roots and clover Trifolium incarnatum seeds. All of them were found to be non-toxic and non mutagenic for testing doses. PMID- 7779178 TI - Measurement of specific and nonspecific IgG4 levels as diagnostic and prognostic tests for clinical allergy. AAAI Board of Directors. PMID- 7779180 TI - Variants of liposarcoma. PMID- 7779181 TI - Negotiating a successful return to work program. AB - This article has examined selected reasons why companies resist implementation of return to work programs. The reasons include many fears that companies can readily justify. Nearly all the fears can be eliminated when the occupational health nurse applies both nursing and management principles. As a specialized line manager in the company, with a specialty in people and systems management, the occupational health nurse is the most likely person to plan and implement a successful program. To design, implement, and manage the plan to a successful end, the occupational health nurse must enhance skills in language, salesmanship, and quantifying results. Success must be measured in both people and dollar terms to have relevance to the company, its bottom line, and its employees. People results, the harder of the two to measure, have value in helping to establish positive attitudes of program participants toward the company. People results also help prevent the development of disability syndrome by ill or injured employees by keeping them connected to work and productivity. People results also can be measured by the change in culture the return to work program is likely to produce among managers and employees. The resulting culture will reflect a sense of caring by the company about employees, and expectation that manipulation of the company by opportunists will be reduced, as scarce company resources will be conserved. The early return to work program is managed within employee capabilities in a therapeutic environment during the recovery process. In the long term, financial success of the return to work program can be measured by reduced costs per claim annually. Using the nursing, management, financial, and marketing principles discussed in this article, the occupational health nurse can improve chances of negotiating implementation of a successful early return to work program. PMID- 7779179 TI - X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction. AB - To clarify the extensibility of thin actin and thick myosin filaments in muscle, we examined the spacings of actin and myosin filament-based reflections in x-ray diffraction patterns at high resolution during isometric contraction of frog skeletal muscles and steady lengthening of the active muscles using synchrotron radiation as an intense x-ray source and a storage phosphor plate as a high sensitivity, high resolution area detector. Spacing of the actin meridional reflection at approximately 1/2.7 nm-1, which corresponds to the axial rise per actin subunit in the thin filament, increased about 0.25% during isometric contraction of muscles at full overlap length of thick and thin filaments. The changes in muscles stretched to approximately half overlap of the filaments, when they were scaled linearly up to the full isometric tension, gave an increase of approximately 0.3%. Conversely, the spacing decreased by approximately 0.1% upon activation of muscles at nonoverlap length. Slow stretching of a contracting muscle increased tension and increased this spacing over the isometric contraction value. Scaled up to a 100% tension increase, this corresponds to a approximately 0.26% additional change, consistent with that of the initial isometric contraction. Taken together, the extensibility of the actin filament amounts to 3-4 nm of elongation when a muscle switches from relaxation to maximum isometric contraction. Axial spacings of the layer-line reflections at approximately 1/5.1 nm-1 and approximately 1/5.9 nm-1 corresponding to the pitches of the right- and left-handed genetic helices of the actin filament, showed similar changes to that of the meridional reflection during isometric contraction of muscles at full overlap. The spacing changes of these reflections, which also depend on the mechanical load on the muscle, indicate that elongation is accompanied by slight changes of the actin helical structure possibly because of the axial force exerted by the actomyosin cross-bridges. Additional small spacing changes of the myosin meridional reflections during length changes applied to contracting muscles represented an increase of approximately 0.26% (scaled up to a 100% tension increase) in the myosin periodicity, suggesting that such spacing changes correspond to a tension-related extension of the myosin filaments. Elongation of the myosin filament backbone amounts to approximately 2.1 nm per half sarcomere. The results indicate that a large part (approximately 70%) of the sarcomere compliance of an active muscle is caused by the extensibility of the actin and myosin filaments; 42% of the compliance resides in the actin filaments, and 27% of it is in the myosin filaments. PMID- 7779182 TI - Serving the community. AB - Occupational health nurse managers have been known to deliver Meals on Wheels, volunteer as Girl Scout leaders, consultants, and trainers, teach first aid and CPR classes to the public, as well as company employees, and work with community leaders and health science students to develop company and community health fairs. The positive image created by such activity for the company, the nurse, and the profession is far reaching and ultimately cost effective. Community service is important now more than ever. It is evident that government cannot solve our problems. Fortunately, the answer to many of our current health and social concerns is in our own backyard our communities. Occupational health managers have a unique opportunity to garner the support of business and industry and contribute to the grassroots movement to improve the health of all Americans. PMID- 7779183 TI - Putting prevention into clinical practice: a program for occupational health nurses. AB - 1. Preventive services are delivered much less frequently than recommended by primary care providers. Many barriers exist. 2. Occupational health nurses can access the valuable, inexpensive resource--"Put Prevention Into Practice" program -to incorporate prevention into illness care, screening, and other visits to their worksite clinics. 3. Use of the "Guide to Clinical Preventive Services," the tools in a kit of materials, and the passport size, client held minirecords can improve the delivery of clinical preventive services. PMID- 7779184 TI - Adherence to worksite exercise programs: an integrative review of recent research. AB - 1. Improving worker physical fitness through worksite exercise programs offers many benefits to the employee and the employer. Unfortunately, a small percentage of workers who begin an exercise program adhere to it. 2. It is essential to design program strategies to promote exercise adherence among persons who do not currently exercise at levels that achieve health benefits. 3. The results of this review of worksite research suggest a number of strategies that were successful in increasing at least short term exercise adherence. 4. Carefully controlled studies are needed to identify specific worksite exercise interventions or combination of interventions that maximize the initiation of exercise as well as short and long term adherence. A combination of strategies improves exercise adherence for at least 6 months, but more research is needed to determine long term maintenance of an exercise program. PMID- 7779185 TI - Occupational low back disability: effective strategies for reducing lost work time. AB - 1. The important variables related to lost work time in this study are: back diagnosis (lumbar disc displacement), history of back surgery, job satisfaction, and employee reluctance to report low back pain to supervisor. 2. The findings support the complexity of low back disability. Lost work time related to low back pain must be managed using a "holistic" approach by addressing all dimensions of a person (physical, emotional, and environmental). 3. To minimize low back disability, occupational health providers should be part of a community task force with representatives from other disciplines who can plan and develop low back disability guidelines and standards of care. PMID- 7779186 TI - Emotional aftermath of a major earthquake: lessons for business. PMID- 7779187 TI - Intraperitoneal foreign body as a cause of acute abdomen in pregnancy. AB - Although surgical textbooks commonly include foreign bodies in the differential diagnosis of acute abdomen, this cause of abdominal pain has not been reported in the obstetric literature. A 35-year-old woman presented at 24 weeks' gestation with right lower quadrant pain and peritoneal signs. The only abnormal finding at exploratory laparotomy was a free-floating intraperitoneal foreign body, presumably left inadvertently during prior surgery. The differential diagnosis of acute abdomen in pregnancy should include intraperitoneal foreign body in any woman with a history of previous abdominal surgery. PMID- 7779188 TI - Decreased platelet counts in infants of diabetic mothers. AB - Infants of diabetic mothers (IDMs) have hematologic indices consistent with increased fetal erythropoiesis, presumably in response to chronic intrauterine hypoxemia. We hypothesized that increased erythropoiesis, as is evident from increased nucleated erythrocyte counts, would be accompanied by interrelated changes in thrombopoiesis and would correlate with maternal glycemic control during pregnancy. We compared absolute nucleated erythrocyte counts and platelet counts obtained in the first 24 hours of life in 32 term, nonasphyxiated IDMs with 47 controls. The IDM group had higher absolute nucleated erythrocyte counts (1.0 +/- 1.3 x 10(9)/L versus 0.4 +/- 0.7 x 10(9)/L; p < 0.05), and lower platelet counts (235 +/- 77 x 10(9)/L versus 348 +/- 79 x 10(9)/L; p < 0.001) than controls. Absolute nucleated erythrocyte counts correlated inversely with platelet counts (r = -0.28; p < 0.02). These neonatal hematologic measurements did not correlate with various parameters of maternal glycemic control. We conclude that in IDMs, increased erythropoiesis is accompanied by decreased platelet counts. These data are consistent with the theory of an erythropoietin induced shift of fetal multipotent stem cell differentiation toward erythropoiesis at the expense of thrombopoiesis. PMID- 7779189 TI - The very low birthweight infant: maternal complications leading to preterm birth, placental lesions, and intrauterine growth. AB - The placental lesions of the very low birthweight (VLBW) infant were investigated in relation to clinical complications leading to preterm birth and evidence of growth impairment. The 249 singleton gestations yielding infants less than 1500 g were grouped according to the clinical complications leading to preterm birth as premature membrane rupture (116/249, 47%) preterm labor (55/249, 22%), pregnancy induced hypertension (PIH, 54/249, 22%), and normotensive abruption (ABR, 24/249, 10%). Specifically excluded from this data set were cases with greater than 2 weeks discordance, fetal congenital anomalies, placenta previa, and maternal medical or gestational diseases such as chronic hypertension and diabetes mellitus, and intrauterine growth retardation (IUGR) as a primary indication for delivery. Placental weight and lesions including decidual vasculopathy and related villous lesions, chronic villitis/intervillositis, and decidual plasmacytosis were considered as variables in analyses in which raw birthweight was the dependent variable and gestational age a confounder. Of the 195 VLBW, 79 (41%) infants from normotensive mothers had lesions of decidual vasculopathy or chronic inflammation. In the VLBW infants from hypertensive mothers, growth restriction was related to markers of decidual vasculopathy. In the absence of maternal hypertension the growth restriction was independently associated with chronic villitis. Decidual vasculopathy (characteristic of PIH) and chronic intrauterine inflammation underlie the complications of many normotensive VLBW infants. The placental lesions in VLBW-IUGR depend on the presence or absence of maternal hypertension. In the absence of maternal hypertension, VLBW-IUGR is associated with chronic inflammation and is independent of decidual vasculopathy. In the presence of maternal hypertension, VLBW-IUGR is directly related to decidual vasculopathy. PMID- 7779190 TI - Labor and delivery complicated by acute mitral regurgitation due to ruptured chordae tendineae. AB - Acute mitral regurgitation due to ruptured chordae tendineae is a dramatic and life-threatening clinical situation. Rarely does this complication occur during pregnancy. We present a case of a 30-year-old woman in week 31 of her pregnancy who developed acute mitral regurgitation, secondary to bacterial endocarditis and ruptured chordae tendineae. This acute event resulted in preterm labor a few hours later. Delivery was uneventful and successful and was followed by open heart surgery 5 days later. A review of the literature on chordae tendineae rupture and resulting mitral regurgitation during pregnancy is presented. PMID- 7779191 TI - Plasma immunoreactive endothelin-1 concentration in cord blood of normal term neonates. AB - Plasma immunoreactive endothelin-1 (ir-ET-1) concentrations in cord blood of 20 term infants were measured by radioimmunoassay. The mean (+/- SEM) ir-ET-1 concentration was 1.04 +/- 0.29 pg/mL. There was no relationship between ir-ET-1 concentrations and race, sex, mode of delivery, and prenatal characteristics, such as cocaine exposure. The current methodologies were reviewed in an effort to explain the differences in ET-1 concentrations reported in various studies. PMID- 7779192 TI - Nonlinearity of heart rate in the neonate. AB - The relationship between heart rate variability and level of illness was examined. Fifteen patients (10 male and 5 female), gestational ages 25 to 42 weeks, postnatal ages 1 to 42 days, birthweights 545 to 4375 g receiving care in the neonatal intensive care nursery were randomly selected. Data from each infant was transferred from the bedside physiologic monitor to a microcomputer for analysis. A severity of illness index (the Children's Hospital Illness Score [CHILLS]) correlated with heart rate variability. Four patterns of heart rate variability were identified: (1) infants whose CHILLS score indicated that they were cardiovascularly normal demonstrated a modest amount of variability; (2) infants with a CHILLS score indicating a moderate amount of illness had heart rates and heart rate variability greater than the normal infants; (3) three infants exhibited bimodality (period doubling) in their heart rates; each of these infants had a CHILLS score that indicated that they were less ill than the most critically ill patients, but sicker than those moderately ill infants without period doubling; and (4) heart rate decreased in the most critically ill infants identified by the CHILLS, but it remained above the heart rate of a healthy newborn; heart rate variability collapsed below that of a healthy newborn. Our data suggest that the variability of heart rate may increase as an infant becomes sicker. When the infant becomes critically ill and unstable, heart rate variability is less than the normal infant. Nonlinear dynamics theory may be a potential model for fitting the data. PMID- 7779193 TI - Sonographic assessment of amniotic fluid in normal twin pregnancy. AB - A sonographic standard for assessment of amniotic fluid volume in normal twin pregnancy is provided. In 210 uncomplicated twin pregnancies, amniotic fluid volume was assessed sonographically, by measuring the total amniotic fluid index (AFI), as well as the deepest single vertical pocket in each sac. The mean AFI was greater than values found in singleton gestations; the AFI increased up to 27 weeks' gestation, and decreased thereafter. It correlated well with measurement of the deepest vertical pocket in each sac (r = 0.71; p < 0.0001). In twin pregnancy at 26 to 32 weeks' gestation a fluid pocket of at least 8 cm was found in 9.8% of cases and did not indicate pathologic states. Either AFI or measurement of the deepest fluid pocket in each sac can be used to assess fluid volume in twin pregnancy. A table specific to twin pregnancy should be used when evaluating twin gestations sonographically. PMID- 7779194 TI - Electromyography with acrylic plug surface electrodes after delivery. AB - Pelvic floor neuromuscular function was evaluated with surface electromyography using acrylic plug electrodes and interactions between neuromuscular function and factors pertinent to the delivery process were explored. Fifty-two women who were primiparas participated in this prospective cohort study. Circumvaginal and circumrectal muscles were assessed. Corrected vaginal-rectal flicks and holds were calculated. The results were compared by delivery route, birthweight, race, lactational status, and delivery anesthetic and to a group of nulliparous subjects. The mean interval from delivery was 46.3 days. Birthweight, race, lactational status, and anesthetic technique were not associated with statistically significant changes in electrical activity, although our ability to detect such differences was low due to the small number of subjects. Women who delivered vaginally had lower vaginal flick voltage than those delivering abdominally. Women who delivered vaginally had lower vaginal flick and hold voltages and rectal flick voltage when compared with nulliparous women studied earlier. Abdominally delivered women had values similar to the nulliparous group. Women delivering vaginally had less surface electromyographic activity in the circumvaginal muscles, implying that vaginal delivery impairs the neuromuscular function of the pelvic floor. PMID- 7779195 TI - Metatropic dysplasia: a case report. AB - A case of metatropic dysplasia is presented, stressing the utility of prenatal diagnosis. PMID- 7779196 TI - Intrauterine diagnosis and management of transient myeloproliferative disorder. AB - Transient myeloproliferative disorders can be associated with hydrops in Down syndrome fetuses. No cases of prenatal management of such a condition have been reported in the literature. We report a case of myeloproliferative disorder diagnosed by cordocentesis at 31 weeks in a Down syndrome fetus with pericardial effusion. A pericardiocentesis was performed at the first signs of hydrops and successfully improved fetal cardiac function, allowing for continuation of pregnancy. PMID- 7779198 TI - Mathematical modeling of fetal organ growth using the Rossavik growth model: IV. Lung. AB - Growth of the fetal lung has been monitored by left lung area (LLA), right lung area (RLA), and total lung area (TLA) from 14 to 41 weeks menstrual age in 116 normal Japanese fetuses. Growth of the fetal heart and chest has also been monitored by heart area (HA) and chest area (CA), respectively. Growth curves for these parameters have been determined by using a Rossavik growth model [p = c(t)k+s(t)]. R2 values of 95.3%, 90.3%, 89.0%, 88.7%, and 92.1% were obtained for CA, HA, LLA, RLA, and TLA, respectively. Variability analysis indicated a progressive increase in variability with fetal age for these five 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 lung growth in the fetus and for identifying pulmonary hypoplasia in utero. PMID- 7779197 TI - Effect of dehydroepiandrosterone sulfate on ophthalmic artery flow velocity waveforms in full-term pregnant women. AB - The possible effects of dehydroepiandrosterone sulfate on orbital circulation in 14 term pregnant women were examined by color Doppler flow mapping and pulsed Doppler ultrasound assessments of ophthalmic artery blood flow velocities before and 3 minutes after the intravenous drug injection. Blood pressure, heart rate, peak systolic velocity, end-diastolic velocity, time-averaged mean peak velocity, and pulsatility index were studied. Dehydroepiandrosterone sulfate injected intravenously had little effect on blood pressure, heart rate, and peak systolic velocity, increasing (p < 0.02) the mean end-diastolic velocity from 3.7 +/- 1.7 to 4.9 +/- 2.0 cm/s (mean +/- SD) and the mean time-averaged mean peak velocity (p < 0.02) from 9.8 +/- 3.2 to 12.1 +/- 3.9 cm/s (mean +/- SD). The mean pulsatility index decreased simultaneously (p < 0.02) from 2.75 +/- 0.79 to 2.29 +/- 0.58 (mean +/- SD). Dehydroepiandrosterone sulfate vasodilates the ophthalmic artery, increasing blood flows in term pregnant women, and similar changes might occur in other cerebral vessels. It seems that this vasodilative effect of dehydroepiandrosterone sulfate is expected for treatment of preeclampsia. PMID- 7779199 TI - Herpes simplex type II infection in monozygotic twins. AB - The unusual occurrence of herpes simplex virus (HSV) type II infection in a set of monozygotic premature twins is described. The cases highlight the difficulty of early diagnosis of HSV disease in the absence of a positive maternal history and cutaneous lesions. Risk factors for mortality and morbidity are discussed. PMID- 7779200 TI - Intrauterine coxsackie virus, group B type 1, infection: viral cultivation from amniotic fluid in the third trimester. AB - We report a case that presents clear evidence of an intrauterine infection of twin fetuses with an enterovirus. The mother had signs and symptoms of chorioamniotitis at 34 weeks' gestation. Coxsackie virus, group B type 1 (CVB1), was cultured from amniotic fluid obtained by transabdominal amniocentesis when the membranes of both fetuses were still intact. Delivery occurred vaginally approximately 24 hours later, following spontaneous rupture of membranes. At birth, both twins showed signs of sepsis. Postpartum, CVB1 was recovered from the mother's cervix, and the newborns' cerebrospinal fluid, nasopharyngeal, and rectal swabs. The present significance of this case is discussed. PMID- 7779201 TI - Changes in blood velocities of fetal circulation in association with fetal heart rate abnormalities: effect of sublingual administration of nifedipine. AB - Nifedipine has been used to treat hypertension in pregnancy, and does not influence fetal or uteroplacental circulations in patients with preeclampsia. A 29-year-old multi-gravid woman presented at 32 weeks' gestation with significant elevation of her blood pressure. After sublingual administration of nifedipine, the blood pressure decreased from 208/122 to 136/96 mm Hg at 30 minutes. In her growth-retarded fetus with abnormal flow velocity waveforms, pulsatility index values for middle cerebral artery and umbilical artery did not change; however, peak systolic velocities, end-diastolic velocities, and time-averaged mean peak velocities for these arteries became significantly elevated. Simultaneously, severe variable decelerations and late decelerations occurred. The adverse effect of nifedipine on fetal circulation might occur in a growth-retarded fetus with abnormal flow velocity waveforms. PMID- 7779202 TI - Successful radiofrequency ablation in a 3-month-old baby with permanent junctional reciprocating tachycardia: a new era in the treatment of incessant life-threatening arrhythmias in infants. AB - We report our experience in treating a 3-month-old baby with accessory atrioventricular pathway by radiofrequency (RF) ablation. The baby was discovered to have incessant supraventricular tachycardia at 4 weeks of age. At that time, two-dimensional echocardiography showed dilated cardiomyopathy. Multiple direct current shocks and multipharmaceutical treatment failed to restore sinus rhythm. Electrophysiology study showed the presence of posteroseptal accessory pathway. Immediately after delivery of two RF pulses, successful ablation of the accessory pathway and complete atrioventricular (AV) block with good junctional escape rhythm were observed. Normal rhythm and AV conduction subsequently returned and all medical treatment was discontinued. To our best knowledge, this is the first case of successful treatment with RF ablation in early infancy. PMID- 7779203 TI - Renal cell carcinoma presenting as hemolytic anemia in pregnancy. AB - A patient presented at 29 weeks' gestation with severe hemolytic anemia. She was subsequently diagnosed as having renal cell carcinoma and had a radical nephrectomy at 31 weeks' gestation, which demonstrated stage I disease. This was followed by a normal vaginal delivery of a healthy infant at term and complete resolution of her anemia. This unusual presentation of renal cell carcinoma in pregnancy is discussed. PMID- 7779204 TI - Benign fetal bradycardias diagnosed by echocardiography. AB - Five cases of benign fetal arrhythmias presented with dramatic pictures of sustained irregular bradycardias. These cases were not associated with structural heart disease, the development of hydrops fetalis, or maternal autoantibodies. In all but one case, the arrhythmias resolved before delivery. Two fetuses had 2:1 atrioventricular block and the other three showed group beating due to blocked atrial trigeminy. With regular intermittent reevaluation, and if no signs of hydrops occur, watchful waiting is the suggested therapeutic modality. PMID- 7779205 TI - Fetal urine production and micturition and fetal behavioral state. AB - The rate of fetal urine production and the incidence of fetal micturition was compared in periods of fetal sleep and awakeness. Sonography and fetal heart rate monitoring were concomitantly performed on 12 normal term pregnancies. Fetal bladder volumes were serially calculated, and the rate of urine production and micturition were compared between the periods of fetal sleep and awakeness. Fetal micturition occurred almost exclusively during periods of fetal awakeness (p = 0.001). There were no demonstrable differences in the rates of urine production during periods of fetal sleep and awakeness. Fetal micturition is behavioral state dependent. Nevertheless, the fetal behavioral state is not a necessary consideration when applying urine production measurements as a test of fetal well being. PMID- 7779206 TI - Antacid bezoar in a premature infant. AB - A premature infant with severe enteroviral infection was treated with Maalox for gastric bleeding. Bezoars formed, which were shown to contain high concentrations of magnesium. An association between antacid administration and bezoar formation in neonates has been previously suggested but has not until now been clearly documented. PMID- 7779207 TI - Cerebral blood flow and EEG changes in preterm infants with patent ductus arteriosus. AB - It is unknown whether the decreased cerebral blood flow seen in infants with a large patent ductus arteriosus is associated with cerebral dysfunction. Decreased cerebral blood flow in adult human and animal models has been associated with altered electroencephalography (EEG), spectral-analyzed EEG, and EEG response to photic stimulation. Cerebral blood flow velocity, EEG, spectral analysis of EEG, and photic alteration of EEG spectra were evaluated in 8 infants before and after closure of a significant patent ductus arteriosus and in 10 control infants without a patent ductus arteriosus. All infants with patent ductus arteriosus had moderate or large shunts associated with a 25% mean reduction in cerebral blood flow velocity. There were no differences, however, in EEG, spectral analysis of EEG, or photic alteration of the spectral analysis for these infants before and after patent ductus arteriosus closure as compared to controls. It is concluded that the degree of decreased cerebral blood flow in infants with a significant patent ductus arteriosus is not sufficient to cause measurable alteration in electrocortical activity. PMID- 7779208 TI - Diagnostic value of pediatric outpatient video-EEG. AB - Outpatient video-electroencephalography (OVEEG) was performed in 100 infants, children, and adolescents with diagnosed (group I, n = 64) or suspected (group II, n = 36) epilepsy. Median monitoring duration was 4 hours. Indications for OVEEG in group I were classification of seizures, reported seizure exacerbation, or onset of new signs. OVEEG indications in group II were repetitive paroxysmal and stereotyped signs of myoclonic movements, fixed gaze, abnormal behavior, or nonmyoclonic motor activity. In group I patients, symptomatic events were recorded in 89%, half of which were seizures. Among group II patients, events were recorded in 67% and were seizures in 22%. Overall, OVEEG was successful in 83% of patients. Compared to a 24-hour inpatient admission for video-EEG monitoring, OVEEG represented cost reductions of 55-80% per patient. We conclude that OVEEG is a cost-effective, useful alternative to continuous inpatient video EEG monitoring in the investigation of selected infants, children, and adolescents with diagnosed or suspected epilepsy. PMID- 7779209 TI - Acute confusional migraine: variant of transient global amnesia. AB - Acute confusional migraine in children and transient global amnesia in adults share a number of similar clinical manifestations. Acute confusional migraine in 6 children (mean age: 11.7 years; range: 7.5-17 years) was characterized by transient episodes of amnesia and acute confusion lasting 1-12 hours. Episodes were preceded by headache and vomiting in 4 patients. In 2 patients acute confusional migraine was the initial symptom. A history of preceding trivial head injury was reported in 3 patients and migraine in 4. Urine and serum drug screens were negative. Cerebral imaging studies and interictal electroencephalograms were normal. Ictal electroencephalograms in 3 patients revealed diffuse or bioccipital delta wave slowing. Recurrent episodes of acute confusional migraine occurred in 2 children during 1-3 years of follow-up. The clinical manifestations of acute confusional migraine in this series of children are similar to those reported in transient global amnesia. The similarity of the clinical manifestations of acute confusional migraine in children and transient global amnesia in adults suggests that these disorders may share a common pathophysiology. PMID- 7779210 TI - Changes of P300 latency with age in childhood epilepsy. AB - Auditory event-related potentials (P300 latency; odd-ball paradigm) were examined in 129 patients with childhood epilepsies and 53 controls. The P300 latency in the patients with epilepsies (373 +/- 39.4 ms) was significantly longer than in controls (356 +/- 38.4), and the prolongation was greatest in the patients with symptomatic partial epilepsies (390 +/- 40.5), mild in those with idiopathic generalized epilepsies (370 +/- 24.3), and minimum in those with idiopathic partial epilepsies (363 +/- 28.9). Abnormal P300 latency occurred at all ages during childhood in patients with symptomatic partial epilepsies, and at older ages in patients with idiopathic generalized epilepsies. The shortening of latency with age was relatively small in patients with epilepsies compared with controls. These results suggest that the prolongation of P300 latency (i.e., existence of cognitive disturbance) displays characteristic changes with age in each epileptic syndrome. PMID- 7779211 TI - Seizures associated with stroke in childhood. AB - Seventy-three consecutive children younger than 17 years of age seen from 1978 to 1992 with acute hemiplegia from stroke, were retrospectively reviewed to evaluate the incidence of seizures and the risks of recurrent seizures after stroke. The population consisted of 56 children with cerebral infarction, 12 with intracranial hemorrhage, and 5 with transient ischemic attack. Children whose strokes occurred in the neonatal period and those secondary to trauma, malignancy, or infection were excluded. Mean follow-up time was 43.5 months (range: 12-156 months). At least 1 seizure occurred in 36 patients (49.3%) and recurrent seizures occurred in 21 patients (28.8%). Recurrent seizures developed more often among patients who had initial seizures with delayed onset (P < .05). In 56 patients with cerebral infarction, 16 of 31 patients (51.6%) with cortical involvement documented by neuroradiologic studies and 1 of 25 patients (4%) without cortical involvement developed recurrent seizures (P < .01). In 12 patients with intracranial hemorrhage, 3 of 10 patients with cortical involvement and none of 2 patients without cortical involvement developed recurrent seizures. It is concluded that seizures commonly occur in childhood stroke. Risk factors for recurrent seizures include later onset of initial seizures and presence of cortical involvement. PMID- 7779212 TI - Stroke in purine nucleoside phosphorylase deficiency. AB - The first documented case of cerebrovascular disease occurring in a 13-year-old girl with purine nucleoside phosphorylase deficiency is reported. This patient, the oldest known survivor with purine nucleoside phosphorylase deficiency, had previously experienced multiple sequential neurologic problems. She presented with episodes of transient left hemiparesis, followed shortly thereafter by dense left hemiplegia. Magnetic resonance imaging revealed a right internal capsule infarct; cerebral angiography revealed vasculopathy of the proximal vessels. Proposed mechanisms for neurologic dysfunction and cerebrovascular disease in purine nucleoside phosphorylase deficiency are discussed. PMID- 7779213 TI - Complete heart block in nonfamilial hyperekplexia. AB - An infant with nonfamilial hyperekplexia had multiple episodes of tonic spasms that mimicked tonic seizures. They were accompanied by complete heart block and apnea. These episodes did not correlate with electroencephalographic epileptiform changes and were partially responsive to clonazepam, valproic acid, and cardiac pacemaker. Sudden death in hyperekplexia may be related to complete heart block and apnea during seizurelike episodes. PMID- 7779214 TI - Optic neuritis with silent cerebral lesions: availability of FLAIR sequences. AB - A 10-year-old male suffering from acute optic neuritis is reported with multiple silent cerebral lesions, which remained visible only with fluid-attenuated inversion recovery sequences at 3-week intervals. Conventional sequences with magnetic resonance imaging did not visualize the lesions. Fluid-attenuated inversion recovery sequences are highly sensitive for the detection of silent lesions in acute optic neuritis. PMID- 7779215 TI - Hemolytic uremic syndrome with particular involvement of basal ganglia and favorable outcome. AB - Two children with hemolytic uremic syndrome and extrapyramidal complications are presented. Neuroimaging studies demonstrated bilateral basal ganglia (striatal) involvement with favorable recovery in both patients. The pathophysiology of the neurologic complications in hemolytic uremic syndrome are probably multifactorial. Our patients suggest a reversible process because both patients recovered clinically and radiographically. Neurologic complications do not always portend a poor prognosis and, in general, involvement of the basal ganglia is associated with favorable outcome. PMID- 7779216 TI - Severe cerebellar atrophy following acute cerebellitis. AB - The clinical course and serial magnetic resonance imaging findings of a 4-year old girl with acute cerebellar ataxia due to acute cerebellitis are described. Multifocal white matter lesions visualized by magnetic resonance imaging in both cerebellar hemispheres in the acute phase disappeared in the convalescent phase. Cerebellar signs became less prominent within 2 weeks, but mild ataxic gait remained. During the follow-up period of 32 months, there was a gradual development of cerebellar atrophy along with a recurrence of cerebellar ataxia. PMID- 7779218 TI - Pre-eruptive neurologic manifestations associated with multiple cerebral infarcts in varicella. AB - A boy, 4 years, 9 months of age, presented with acute hemiplegia, lethargy, ataxia, and dysarthria 24 hours prior to the eruption of typical varicella exanthem. Magnetic resonance imaging findings were typical of multiple cerebral ischemic infarcts. It is suggested that during the period of secondary viremia varicella zoster virus invaded the cerebral blood vessels causing vasculopathy and cerebrovascular infarcts. PMID- 7779217 TI - Vertebral artery compression due to head rotation in thalamic stroke. AB - Vertebral artery compression from head turning has been described in adults, especially in those who have spondylosis of the spine and osteophytes. There are no reports that demonstrate vertebral artery compression due to head turning in children without vertebral abnormalities. A child is reported with thalamic stroke in whom cerebral arteriography revealed vertebral artery compression on head turning. Blood flow in the vertebral artery, however, could be demonstrated by Doppler ultrasonography with the head in the midline. It is concluded that the vertebral artery is vulnerable to mechanical compression in the neck even in the absence of bony abnormalities. PMID- 7779219 TI - Acute transverse myelitis and brainstem encephalitis associated with hepatitis A infection. AB - A 4-year-old boy became paraplegic during the course of hepatitis A infection. There were significant magnetic resonance imaging changes in the cervical spinal cord and brainstem. The patient's cervical myelopathy resolved entirely after 10 weeks. PMID- 7779220 TI - Primary malignant melanoma of meninges: atypical presentation of subacute meningitis. AB - Primary malignant melanoma of the meninges is described in a 5-year-old boy who presented with a 3-month history suggestive of subacute meningitis. Clinically the diagnosis of tuberculous meningitis was made and antituberculous treatment was begun. Despite this treatment, the patient's condition continued to deteriorate. Through cytologic examination of the cerebrospinal fluid malignant melanoma cells were identified, emphasizing the importance of this investigation in children with atypical meningitis. The diagnosis of malignant melanoma of the meninges was confirmed on brain biopsy. PMID- 7779221 TI - Visual system electrodiagnosis in neurologic disease of childhood. AB - Electrodiagnostic examination of the visual system includes visual evoked potentials and electroretinography. These tests can be applied to all ages. Pitfalls in the clinical ophthalmologic examination of children, such as optic nerve pallor and pigmentary retinopathy, can be clarified by these tests. Investigation of neurodegenerative disease may be directed to the most likely defect by results of visual evoked potential testing and electroretinography. The child who is unable to meaningfully communicate sensory experience can be objectively evaluated by these studies. Familiarity with the applications and limitations of these tests will allow the examiner to choose the appropriate setting and time to apply each of them. PMID- 7779222 TI - Effective care in pregnancy and childbirth: a synopsis. AB - Evidence about the effects of care practices is not a sufficient guide to the most appropriate care. Those who provide care, who receive care, who advocate care, or who pay for care must choose on the basis of many factors: personal experience, personal preference, personal values, availability of resources and facilities, and a myriad of other considerations, among which knowledge of the effects of care is certainly important. This knowledge is essential for choices to be properly informed. The most reliable evidence about the effects of care is provided by randomized controlled trials. Unfortunately, this evidence is not readily accessible. It is scattered through a large number of journals throughout the world, and is hidden among a mass of weak, inadequate, and sometimes frankly misleading studies. Those who wish to use all the valid evidence must rely on properly prepared, up-to-date, systematic reviews. The Cochrane Collaboration has taken on the task of preparing, maintaining, and disseminating reviews of randomized trials of health care, published electronically as the Cochrane Database of Systematic Reviews. The reviews are provided by a number of Collaborative Review Groups, and the Cochrane Pregnancy and Childbirth Database is the first specialty database to appear. It is regularly updated to incorporate data that have become available since the previous issue. PMID- 7779223 TI - Baby-Friendly Expert Work Group in the United States: blowing the whistle. PMID- 7779224 TI - Changes in cesarean delivery in the United States, 1988 and 1993. AB - The rate of cesarean delivery in the United States (22.8% in 1993) has remained stable since the mid-1980s after dramatic increases during the 1970s and early 1980s. The primary cesarean rate (16.3 cesareans in 1993 per 100 women with no history of previous cesarean delivery) was also stable from 1988 to 1993. During this same period, the rate of vaginal birth after previous cesarean (VBAC) doubled, from 12.6 to 25.4 percent. In both 1988 and 1993, rates of cesarean delivery were higher in the South than in other regions, for mothers 35 years or older than for younger women, for proprietary than for nonprofit or state and local government hospitals, and for women with private insurance than for women with Medicaid or self-pay as the expected source of payment. Even if VBAC rates continue to increase at the same rate as in the past, the Year 2000 goal of an overall cesarean rate of 15 percent cannot be met without reducing the primary cesarean rate by 50 percent. PMID- 7779225 TI - Midwifery care and medical complications: the role of risk screening. AB - This study analyzed the 147,293 births attended by midwives in the United States in 1989. It used the revised and expanded standard national certificate of a live birth, which for the first time systematically records prenatal medical risk, intrapartum complications, obstetric procedures, and birth outcomes. It builds on earlier findings of positive outcomes for midwife-attended births to examine the prenatal medical risk profile of mothers served by midwives, the performance of obstetric procedures by midwives in different birth settings, more specific measures of outcomes, and possible explanations for these findings. Although midwives attending births in birth centers and homes generally serve mothers who are at much less than average medical risk, and in cases of intrapartum complications risk screening appears to occur, nurse-midwife-attended births in hospitals involve mothers whose risk profiles compare with, and in some cases are worse than, the national average. Nonetheless, the outcomes of these births are better than the national average. Mothers attended by midwives in birth centers and homes also have a different pattern of prenatal care, which begins later and includes fewer visits, but gives more apparent attention to self-care, and results in less smoking and alcohol use and greater weight gain. PMID- 7779226 TI - What predicts breastfeeding intention in Mexican-American and non-Hispanic white women? Evidence from a national survey. AB - We examined the effects of a series of predictors on the prepartum intention to breastfeed in both Mexican-American and non-Hispanic white women. A national sample included 430 Mexican-American women and 3659 non-Hispanic white women who had a pregnancy in 1988. Prenatal behavioral, sociodemographic, and biomedical information was obtained through the 1988 National Maternal and Infant Health Survey. Two dependent variables were constructed to identify significant predictors of breastfeeding intention: exclusive versus partial and bottle feeding, and exclusive and partial versus bottle-feeding. Results from the multiple logistic regression models indicated that advice to breastfeed at prenatal care was the strongest predictor of intentions in both Mexican-American (OR = 2.15, OR = 1.86) and non-Hispanic white mothers (OR = 2.29, OR = 3.61). In Mexican-Americans the father's being Hispanic was negatively associated with breastfeeding intention (OR = 0.63). In non-Hispanic whites the advice to formula feed at the Women, Infants, and Children's nutrition program was a significant negative predictor of breastfeeding intention (OR = 0.33, for exclusive and partial breastfeeding vs exclusive bottle-feeding). These results have important implications for public health policy and practice. PMID- 7779227 TI - Women's reasons for not seeking prenatal care: racial and ethnic factors. AB - Our objective was to determine if there were differences in the reasons for not seeking early prenatal care among low-income black, Hispanic, and white women who had four or fewer prenatal care visits or care only in the third trimester, and who gave birth at Denver General Hospital in Colorado. Data were gathered from 606 women (48% Hispanic, 26% black, 26% white) after delivery, using a 188-item questionnaire and abstracted medical charts. The most important reasons for not seeking early prenatal care were attitudinal (47%), financial (26%), and structural and system problems (8.5%). Financial reasons were more important to white than to black or Hispanic women, and attitudinal reasons were more important to black and Hispanic than to white women. The analysis showed that education and marital status were sometimes confounding variables. Clear differences in reasons for not seeking prenatal care were reported by women of dissimilar racial and ethnic groups in this public hospital. Cultural variations in women's views should be taken into account in developing programs intended to improve prenatal care and pregnancy outcome in Denver. PMID- 7779228 TI - Anemia and insufficient milk in first-time mothers. AB - Insufficient milk is a poorly understood problem that is often identified as a major reason for early discontinuation of breastfeeding. This study explored the relationship between anemia and insufficient milk in 630 first-time mothers. The frequency of anemia (postpartum hemoglobin < 10 g/dL) was 22 percent. Anemic mothers reported a higher level of symptomatology associated with insufficient milk and were more frequently classified as having insufficient milk syndrome. Mothers with the syndrome reported a shorter period of full breastfeeding, and weaned at an earlier age. They identified not having enough milk, baby nursing too often, and baby not gaining enough weight as the main reasons for discontinuing breastfeeding, compared with baby's disinterest and conflicts with school or work as main reasons among mothers not reporting symptoms related to insufficient milk syndrome. The study results suggest that anemia is associated with the development of insufficient milk, which in turn, is related to duration of full breastfeeding and to age at weaning. PMID- 7779229 TI - Variables related to nausea and vomiting during pregnancy. AB - Seventy to 90 percent of all pregnant women experience nausea, and 50 percent have at least one episode of vomiting or retching. A continuous measure was used to quantify symptoms of nausea with or without vomiting or retching during pregnancy in 126 women. Relationships between symptoms and selected variables were evaluated. Nausea with or without vomiting or retching was associated with maternal age, occupation, parity, cigarette smoking, infant gender, and the personality trait of independence. Significant associations were entered into multiple regression equations. Fourteen percent of the variation in symptoms overall, 25.1 percent of the variation in nausea symptoms, and 16.6 percent of the variation in vomiting or retching symptoms were explained by a combination of these selected independent variables. Although this study found associations, independent variables contributed little to predicting or explaining the presence and severity of nausea and vomiting during pregnancy. More sensitive measures and evaluation are required to understand and treat this perplexing phenomenon. PMID- 7779230 TI - Research & writing basics: elements of the case study. PMID- 7779231 TI - Minimizing factors that impair wound healing: a nursing approach. AB - Chronic wounds present tremendous challenges to the healthcare team. Unlike acute wounds that usually progress neatly in a timely manner through the inflammation, proliferation and maturation phases of the healing process, chronic wounds deviate from the predictable sequence of regeneration and repair. To aid the healing process, there are five questions a nurse should ask when assessing a wound: "What is it?" "At what stage in the wound healing process is this wound?" "Is this wound healing at the expected rate?" "What local factors exist that may be delaying the healing process of this wound?" and "What systemic factors exist that may be delaying the healing process of this wound?" At various points in the process, specific concerns then need to be targeted. Initially, prevent or control infection. Then optimize exudate control and remove foreign bodies. Finally, prevent premature wound closure or contracture, especially in infected or undermining wounds. When the five assessment questions are answered and specific concerns have been addressed, the wound should proceed through the normal phases of the wound healing process. Throughout the process, attention to factors such as nutrition, systemic conditions, and perfusion is essential if healing is to be optimized. PMID- 7779232 TI - Standardizing performance-based criteria for support surfaces. AB - Due to the sparsity of prospective, controlled, clinical studies on the efficacy of and the lack of standardized information about support surfaces, current literature does not clearly define how these surfaces address patient needs. Standardization would help healthcare professionals make better informed decisions about the use of support surfaces. Standardization would also help researchers design and implement controlled, clinical studies by defining characteristics of surface evaluation, making it possible to replicate research activities. The first step toward standardization is to develop a performance based set of criteria for classifying these surfaces. With respect to the three purposes identified: comfort, postural control and pressure management, only parameters that can be measured noninvasively, have been considered. The nine parameters are life expectancy of the surface, skin moisture control, skin temperature control, redistribution of pressure, product service requirements, fail safety, infection, flammability, and patient/product friction. Specific guidelines for each of these nine parameters are discussed in depth. With testing and evaluation of support surfaces standardized, clinicians will be able to choose a surface to meet the needs of patients the same way they make other treatment decisions: based on outcomes and the results of controlled, clinical studies. PMID- 7779234 TI - Pressure reduction with a hospitalized population using a mattress overlay. AB - Billions of dollars are spent each year on treating pressure ulcers. With healthcare costs climbing and reform the order of the day, it is essential for researchers to identify a device which reduces pressure, is easy to use and is cost effective. This study used a Mini-Tipe pressure sensor to measure pressure readings over the sacral and trochanter areas of 17 subjects identified as being at risk for skin breakdown. Pressures were compared on a standard hospital mattress and an anatomically contoured mattress overlay. There was a 48 percent reduction in mean pressures over the sacral area and a 23 percent reduction over the trochanter. No correlations between pressures and demographic data were identified. Further research is warranted to determine the effects of variables found in an "at risk" population on pressure reduction with various products. PMID- 7779233 TI - Case study: a modified topical treatment regimen for sodium warfarin-induced necrotizing fasciitis. AB - This case study describes an atypical case of refractory, sodium warfarin-induced necrotizing fasciitis and myonecrosis. This patient did not initially receive surgical debridement and systemic antibiotics, the standard treatment for necrotizing fasciitis of bacterial origin. This patient's wound care regimen began with silver sulfadiazine and wet-to-dry dressings, modified to initial cleansing with a zinc-saline solution, followed with application of a zinc-saline wet dressing, impregnated with an aluminum hydroxide ointment. The patient experienced pain relief after the first application. After 4 weeks, the necrotic tissue sloughed off, the early signs of healing appeared making surgical debridement possible. Therapy with the zinc-saline dressings was continued and restoration of all tissues was documented within 225 days. If aggressive surgical therapy is not an option, the prevention of secondary complications such as infection becomes the goal of treatment until the necrotic process stops and healing begins. For this goal, a moist environment may be the optimal choice for topical therapy. PMID- 7779235 TI - Important information to consider regarding previously published tissue interface pressures. PMID- 7779236 TI - Comparing healing rates across studies is the vision, but first, a correct equation please! PMID- 7779237 TI - Using the nursing process to solve a problem: post-op tape blisters. AB - ET nursing consultation was requested for the treatment of ten cases of tape blisters within six months, the majority of which were post-op following hip surgery. When the ET nursing staff was asked to develop a standard treatment protocol for these blisters, they used the nursing process. They identified the problem, assessed the situation, planned and implemented a response, and evaluated the results in an ongoing manner. It was then theorized that lack of "stretch" in the tape might be causing the tape blisters. After five stretch tapes were assessed for ease of removing the paper backing, handling, application, flexibility, and adhesion, one tape was preferred by the operating room and nursing unit staffs and was put into routine use in October 1992. No further blisters have been noted since this change was made. By using the nursing process, the authors ultimately eliminated post-op tape blisters in the facility. PMID- 7779238 TI - The nurse's role in sexual counseling. AB - Sexual concerns can result from many common illnesses or treatments. If problems or potential problems are left unresolved, the patient's self-concept is decreased and adjustment to altered body image or altered bodily functions are difficult. Sexuality should be a part of the plan of care for patients as are nutrition, elimination and mobility. If sexuality and sexual activity are part of a patient's normal life, they must be considered with other components of daily living. Jack Annon developed a model for sexual counseling called PLISSIT: Permission, Limited Information, Specific Suggestions, and Intensive Therapy. This short-term supportive counseling during hospitalization can enhance self esteem and assist with adaptation. In providing this support, nurses can help patients to know and understand their own abilities and disabilities brought on by their illness or surgery, allowing them to adjust accordingly. PMID- 7779239 TI - Chronic imipramine administration alters the activity and phosphorylation state of tyrosine hydroxylase in dopaminergic regions of rat brain. AB - In the present study the influence of imipramine, a tricyclic antidepressant, on the expression and function of tyrosine hydroxylase (TH) in dopaminergic rat brain regions was examined. Chronic administration of imipramine (18 days) decreased levels of TH enzyme activity in ventral tegmental area (VTA) and substantia nigra (SN), dopaminergic cell body regions, as well as in caudate putamen (CP), nucleus accumbens (ACB), prefrontal cortex (PFC), and olfactory tubercle (OT), dopaminergic terminal fields. These effects were dependent on chronic drug treatment, as imipramine administration for 1 or 7 days did not significantly influence levels of TH activity in either SN or VTA. In contrast to drug regulation of enzyme activity, chronic imipramine treatment did not decrease levels of TH immunoreactivity in any of the dopaminergic cell body or terminal field regions studied, although levels of TH immunoreactivity were decreased in locus coeruleus (LC) as previously reported. However, imipramine treatment increased levels of TH back phosphorylation in VTA, suggesting that the antidepressant-induced decrease in levels of TH activity is a result of decreased phosphorylation of the enzyme. These results demonstrate that imipramine treatment regulates levels of TH enzyme activity in dopaminergic brain regions, and may account for some of the previously observed effects of these drugs on dopaminergic function. Finally, imipramine regulation of TH enzyme activity in VTA and immunoreactivity in LC was observed in Sprague Dawley, but not Wistar rats, demonstrating that different rat strains exhibit different biochemical responses to antidepressant treatment. PMID- 7779240 TI - Depression of thalamic metabolism by lorazepam is associated with sleepiness. AB - Though it is well recognized that the pharmacological actions of benzodiazepines are mediated by facilitation of GABAergic neurotransmission, the consequences of these changes in regional brain function are not well understood. This study measured regional brain glucose metabolism using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in normal controls (n = 21) investigated with and without lorazepam (30 micrograms/kg IV) and with flumazenil given after lorazepam (n = 9). Lorazepam markedly decreased metabolism in thalamus (23 +/- 8%) and occipital cortex (19 +/- 8%), and flumazenil partially reversed these changes. Changes in metabolic activity in thalamus were significantly correlated with lorazepam-induced sleepiness (r = .69, df 20, p < .0005) and there was a trend of an association between the reversal by flumazenil of lorazepam-induced change in thalamus and in sleepiness (r = .63, df 8, p = .07). Benzodiazepine-induced changes in thalamic activity may account for their sedative properties. PMID- 7779241 TI - Treatment of polydipsia and hyponatremia in psychiatric patients. Can clozapine be a new option? AB - Polydipsia occurs frequently in chronic schizophrenic patients, some of whom develop intermittent hyponatremia. Most therapeutic efforts have tried to control the hyponatremia. Four schizophrenic patients, followed for more than one year, showed improvement on clozapine. Case 1 was an outpatient without history of hyponatremia who improved from polydipsia and psychosis. The last three were inpatients with polydipsia, intermittent hyponatremia, and psychosis who showed minimal improvement of psychosis but significant decrease in polydipsia and water intoxication. Case 2 relapsed to polydipsia when clozapine was discontinued on two occasions. Case 3 demonstrated polyuria during 39% of days before clozapine and in 0% of days after two weeks of clozapine. In case 4, most baseline sodium levels were abnormal, but all became normal after clozapine. A time-series analysis for intervention effects showed a significant effect of clozapine (p = .017). The limited information provided by these case reports suggest the need for controlled studies of the clozapine effect on polydipsic patients. PMID- 7779242 TI - Effects of D3/D2 dopamine receptor agonists and antagonists on prepulse inhibition of acoustic startle in the rat. AB - Prepulse inhibition (PPI) is the normal reduction in a startle response that occurs when a weak stimulus ("prepulse") precedes the startling stimulus by 30 to 500 msec. Schizophrenic patients are deficient in this operational measure of sensorimotor gating; therefore, animal models of deficient PPI may provide information useful in the understanding and treatment of schizophrenia. Prepulse inhibition is disrupted in rats by systemic administration of direct dopamine agonists having affinity for the D2 subtype family (D2, D3, and D4) of dopamine receptors. This study tested the hypothesis that dopamine agonists and antagonists with different affinities for D3 and D2 receptors differ in their relative potencies to modulate PPI. The dopamine agonists quinpirole, 7-hydroxy N,-N-di-n-propyl-2-aminotetralin (7-OH-DPAT) and apomorphine were approximately equipotent in decreasing PPI. Pretreatment with haloperidol (13 to 130 nmol/kg sc), but not equimolar doses of UH 232, prevented the disruption of PPI produced by the highest dose (0.6 mumol/kg sc) of each agonist. Given the 100-fold higher affinity of haloperidol relative to UH 232 for D2 receptors, and equal relative affinities of these antagonists for D3 receptors, these data are consistent with previous studies suggesting that dopamine agonists may modulate PPI in the rat through the D2 subtype of dopamine receptors. PMID- 7779244 TI - Fluoxetine and oculomotor activity during sleep in depressed patients. AB - The effects of fluoxetine on automated measures of electrooculographic (EOG) and electromyographic (EMG) activity were evaluated in 41 patients with nonpsychotic, major depressive disorder. Sleep EEG evaluations were conducted at baseline, while patients were symptomatic and unmedicated, and following four to five weeks of treatment with fluoxetine (20 mg). The number of eye movements (> 75 microV) and the amplitude of EOG and EMG activity increased significantly on treatment in REM, stages 1, 2, and slow-wave sleep. All patients showed EOG and EMG abnormalities in at least one stage of sleep. Thirty-four percent of patients showed increased EOG and EMG activity on treatment in every sleep stage. It is suggested that fluoxetine-induced oculomotor abnormalities are likely to be the result of increased availability of serotonin and secondary dopaminergic effects. PMID- 7779243 TI - Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment. AB - The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment. PMID- 7779246 TI - Psychopharmacology: finding one's way. AB - The paper recalls the experiences of the author over the past forty-eight years in a field which later became known as psychopharmacology. The author began in physical chemistry and traditional pharmacology. His interest in the nervous system stemmed from X-ray diffraction studies on the structure of living myelin, and led, by way of studies on the distribution of cholinesterases and the effects of atropine, to the study of the effects of drugs on the electrical activity of the brain in the conscious animal. At the clinical level it included studies of the effects of drugs on catatonic schizophrenic stupor. These studies took place before the discovery of chlorpromazine. They led to the creation, in 1951, of the Department of Experimental Psychiatry in Birmingham, England, the first department of its kind in the world. The department included neurochemical, electrophysiological, and animal behavior laboratories and a strong clinical facility (the Uffculme Clinic). The first blind trial of chlorpromazine was carried out in that department in 1953 and 1954. The existence of families of neuroregulatory compounds, having uneven distribution in the brain, and exerting regional chemical field effects in relation to function was postulated on the basis of experimental and clinical findings. The work of colleagues and participants in the various studies is gratefully acknowledged in the text. In 1954 the author served as convening executive secretary of the first International Symposium on Neurochemistry at Oxford, England, the first meeting of its kind. He came to the United States in 1957 and founded, and served as first director of, the new Clinical Neuropharmacology Research Center, now the Center for Neuroscience at St. Elizabeth's Hospital, Washington, DC. He directed this program from 1957 to 1963. Subsequent activities at Johns Hopkins, the World Health Organization, and the International Brain Research Organization (IBRO) are recalled. In 1961 he was elected first president of the American College of Neuropsychopharmacology. In looking back, he notes the sparse and personal nature of the field in the late 1940s and early 1950s, its explosive growth in the wake of the major clinical discoveries, and above all, the emergence of a new science through the interaction of neurochemistry, electrophysiology, studies of animal behavior, and the refinement of the clinical trial. He regards the emergence of concepts of regional chemistry of the brain as particularly significant, and feels that psychopharmacology is ideally positioned to act as an intermediary between classical pharmacology and quantrum biology. The transdisciplinary nature of psychopharmacology provides a template for a comprehensive psychiatry of the future--a discipline which is now positioned to lead.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7779245 TI - The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome. AB - Recent studies indicate that antidepressant drugs with potent serotonin reuptake inhibiting properties are effective in reducing the symptoms of premenstrual syndrome (PMS). In order to elucidate whether all antidepressant drugs are equally effective in the treatment of PMS or whether potent serotonin reuptake inhibition is a prerequisite for reducing premenstrual complaints, women suffering from severe PMS were treated daily for three menstrual cycles with a selective serotonin reuptake inhibitor, paroxetine (n = 22), or with a selective noradrenaline reuptake inhibitor, maprotiline (n = 21); in addition, a placebo group was included (n = 22). Six symptoms (irritability, depressed mood, tension/anxiety, increased appetite/craving for carbohydrates, bloating, and breast tenderness) were rated by the participants daily throughout the study. With respect to all outcome measurements, the symptom reduction obtained with paroxetine was significantly superior to that obtained with placebo; with respect to irritability, increased appetite/carbohydrate craving, bloating, and breast tenderness, as well as global self-rating, paroxetine was significantly superior also to maprotiline. The clear-cut superiority of paroxetine over maprotiline indicates that not all antidepressant drugs are equally effective in the treatment of PMS; rather, like panic disorder and obsessive compulsive disorder, but in contrast to depression, PMS apparently responds better to serotonin reuptake inhibitors than to antidepressants with a noradrenergic profile. PMID- 7779247 TI - Disease susceptibility, transplantation and the MHC. PMID- 7779248 TI - A new era for carnitine? PMID- 7779249 TI - 3rd Jenner International Glycoimmunology Meeting. PMID- 7779250 TI - Cytokine-binding proteins: stimulating antagonists. AB - Cytokine-binding proteins (CBPs) block the ability of cytokines to interact with their receptors. These agents can potentially provide a means of treating pathological conditions that have a significant cytokine involvement. However, a major drawback of such approaches relates to the fact that CBPs stabilize the cytokine in the form of a cytokine-CBP complex in vivo. Here, Bernard Klein and Herve Brailly discuss the possibility that CBPs behave either as agonists or antagonists according to their pharmacokinetic characteristics in vivo, and suggest a mechanism by which stable complexes might be cleared from the system. PMID- 7779251 TI - Polarization of Th-cell responses: a phylogenetic consequence of nonspecific immune defence? AB - CD4+ T helper (Th)-cell responses are polarized into Th1 and Th2 types. Here, Paul Garside and Allan McI. Mowat propose that this is an evolutionary consequence of the relationship between specific adaptive immunity, individual components of the nonspecific inflammatory response and different types of infection. This concept has important implications both for understanding protective immunity and for vaccine design and delivery. PMID- 7779252 TI - Ligands for the T-cell receptor: hard times for avidity models. AB - T-cell activation occurs when the T-cell receptor (TCR) binds to a self major histocompatibility complex (MHC) molecule carrying a specific peptide. Small changes in peptide structure can alter or inhibit this response. Although this phenomenon is normally attributed to a lowering of the avidity of the ligand for its receptor, recent data suggest that conformational changes in the receptor itself may be playing a critical role, as discussed here by Charles Janeway. PMID- 7779253 TI - An important role for intestinally derived T cells in respiratory defence. AB - Margaret Dunkley, Reinhard Pabst and Allan Cripps discuss the role of intestinally derived T cells in protecting the lung against Gram-negative bacterial infection. They describe the factors directing T-cell migration from gut-associated lymphoid tissue to lung, and focus on the role of T cells and T cell-derived cytokines in bacterial clearance from the lung. PMID- 7779254 TI - The human immunoglobulin VH repertoire. AB - A complete map of the human immunoglobulin VH locus on chromosome 14 has recently been constructed. The locus is 1100kb in length and contains 51 functional VH segments interspersed amongst a similar number of pseudogenes. Here, Graham Cook and Ian Tomlinson review the organization of the locus, its polymorphism and the repertoire it encodes. PMID- 7779255 TI - Molecular chaperones and the biosynthesis of antigen receptors. AB - Oligomeric antigen receptors must fold and assemble in the endoplasmic reticulum (ER) before they can be expressed on the surface of lymphocytes. It is increasingly evident that these processes are facilitated by molecular chaperones. Here, Jeffrey Melnick and Yair Argon review the known ER chaperones, summarize their roles in the maturation of antigen receptors, and discuss how they may affect lymphocyte differentiation and function. PMID- 7779256 TI - Combination therapies for HIV infection. PMID- 7779257 TI - Circulating adhesion molecules in inflammatory and atherosclerotic vascular disease. PMID- 7779258 TI - Sarcoidosis and malaria. PMID- 7779259 TI - Conserved nonplanar heme distortions in cytochromes c. AB - A nonplanar distortion of the heme of c-type cytochromes is conserved in the proteins isolated from diverse species based upon a comprehensive analysis of available high-resolution X-ray crystal structures. This distortion is induced through the cysteine thioether linkages between the porphyrin pyrrole groups and the polypeptide and results in an asymmetric pyrrole distortion. This asymmetry in the heme distortion is also conserved. For other heme proteins which lack these covalent bonds, nearly planar porphyrins are observed. Resonance Raman evidence indicates that nonplanar distortion of porphyrins containing metals, like iron, with large core sizes (> or = 2.00 A) is energetically unfavorable and can occur only in the presence of significant environmental perturbations. Further, energy minimization and dynamics calculations on the ferric form of yeast iso-1-cytochrome c, starting from the crystallographic coordinates and using a molecular mechanics force field which accurately reproduces nonplanar distortions in metalloporphyrins, suggest that this distortion is indeed maintained by the protein tertiary structure. It is proposed that this protein linked heme distortion modulates electron transfer function through modification of redox potentials of the porphyrin ring and the protein binding properties of c type cytochromes. PMID- 7779260 TI - Unfolding of tertiary structure of Halobacterium halobium flagellins does not result in flagella destruction. AB - The structure of Halobacterium halobium R1M1 flagella is investigated by the methods of scanning microcalorimetry, circular dichroism, and electron microscopy. It is shown that melting curves of flagella in solutions with a different concentration of NaCl display only one peak of heat capacity that corresponds to one cooperatively melting domain. It is found that flagella do not dissociate after melting. The possible structural organization of archaebacterial flagella is discussed. PMID- 7779261 TI - Conformation of the transmembrane domain of the c-erbB-2 oncogene-encoded protein in its monomeric and dimeric states. AB - The human c-erbB-2 oncogene is homologous to the rat neu oncogene, both encoding transmembrane growth factor receptors. Overexpression and point mutations in the transmembrane domain of the encoded proteins in both cases have been implicated in cell transformation and carcinogenesis. In the case of the neu protein, it has been proposed that these effects are mediated by conformational preferences for an alpha-helix in the transmembrane domain, which facilitates receptor dimerization, an important step in the signal transduction process. To examine whether this is the case for c-erbB-2 as well, we have used conformational energy analysis to determine the preferred three-dimensional structures for the transmembrane domain of the c-erbB-2 protein from residues 650 to 668 with Val (nontransforming) and Glu (transforming) at position 659. The global minimum energy conformation for the Val-659 peptide from the normal, nontransforming protein was found to contain several bends, whereas the global minimum energy conformation for Glu-659 peptide from the mutant, transforming protein was found to be alpha-helical. Thus, the difference in conformational preferences for these transmembrane domains may explain the difference in transforming ability of these proteins. The presence of higher-energy alpha-helical conformations for the transmembrane domain from the normal Val-659 protein may provide an explanation for the presence of a transforming effect from overexpression of c-erbB-2. In addition, docking of the oncogenic sequences in their alpha-helical and bend conformations shows that the all-alpha-helical dimer is clearly favored energetically over the bend dimer. PMID- 7779262 TI - Isolation and partial characterization of basic proteinases from stem bromelain. AB - Crude bromelain extracts from pineapple stems (Ananas comosus) were fractionated by two-step FPLC-cation-exchange chromatography. At least eight basic proteolytically active components were detected. The two main components F4 and F5 together with the most active proteinase fraction F9 were characterized by SDS PAGE, mass spectroscopy, multizonal cathodal electrophoresis, partial amino acid sequence, and monosaccharide composition analysis. F9 amounts to about 2% of the total protein and has a 15 times higher specific activity against the substrate L pyroglutamyl-l-phenylanalyl-l-leucine-p-nitroanilide (PFLNA) than the main component F4. The molecular masses of F4, F5, and F9 were determined to 24,397, 24,472, and 23,427, respectively, by mass spectroscopy. Partial N-terminal amino acid sequence analysis (20 amino acids) revealed that F9 differs from the determined sequence of F4 and F5 by an exchange at position 10 (tyrosine- >serine) and position 20 (asparagine-->glycine). F4 and F5 contained fucose, N acetylglucosamine, xylose, and mannose in ratio of 1.0:2.0:1.0:2.0, but only 50% of the proteins seem to be glycosylated, whereas F9 was found to be unglycosylated. Polyclonal antibodies (IgG) against F9 detected F4 and F5 with tenfold reduced reactivity. The pH optimum of F4 and F5 was between pH 4.0 and 4.5 and for F9 close to neutral pH. The kinetic parameters for PFLNA hydrolysis were similar for F4 (Km 2.30 mM, kcat 0.87 sec-1 and F5 (Km 2.42 mM, kcat 0.68 sec-1), and differed greatly from F9 (Km 0.40 mM, kcat 3.94 sec-1). PMID- 7779264 TI - A collaborative approach to using new technologies for the management of heart disease at the University of Ottawa Heart Institute. AB - Nursing in the Cardiac Operating Rooms and Catheterization Laboratories at the University of Ottawa Heart Institute has played a collaborative role in advancing and promoting the use of new technologies for treating heart disease. This has been demonstrated in the Catheterization Laboratories with the introduction of such procedures as angioplasties, atherectomies, stents and rotablators and in the Cardiac Operating Rooms with heart transplants and total artificial heart implants. Currently, nurses in the Operating Rooms are actively involved in research on the electrohydraulic totally implantable ventricular assist device (EVAD) which is an internal pump to assist the left ventricle to eject blood into the systemic circulation. Clinical and research professionals work together so that any problems related to using new technologies are identified and solved during both the planning and implementation stages. This article will focus on the collaborative process as it was used for the Artificial Heart Program and on new technologies related to the implant of the electrohydraulic ventricular assist device. PMID- 7779263 TI - Physicochemical and immunological characterization of the type E botulinum neurotoxin binding protein purified from Clostridium botulinum. AB - Type E botulinum neurotoxin is produced by Clostridium botulinum along with a neurotoxin binding protein which helps protect the neurotoxin from adverse pH, temperature, and proteolytic conditions. The neurotoxin binding protein has been purified as a 118-kDa protein. Secondary structure content of the neurotoxin binding protein as revealed by far-UV circular dichroism spectroscopy was 19% alpha-helix, 50% beta-sheets, 28% random coils, and 3% beta-turns. This compared to 22% alpha-helix, 44% beta-sheets, 34% random coils, and no beta-turns of the type E botulinum neurotoxin. The complex of the two proteins revealed 25% alpha helix, 45% beta-sheets, 27% random coils, and 3% beta-turns, suggesting a significant alteration at least in the alpha-helical folding of the two proteins upon their interaction. Tyrosine topography is altered considerably (28%) when the neurotoxin and its binding protein are separated, indicating strong interaction between the two proteins. Gel filtration results suggested that type E neurotoxin binding protein clearly complexes with type E neurotoxin. The interaction is favored at low pH as indicated by an initial binding rate of 8.4 min-1 at pH 5.7 compared to 4.0 min-1 at pH 7.5 as determined using a fiber optic based biosensor. The neurotoxin and its binding protein apparently are of equivalent antigenicity, as both reacted equally on enzyme-linked immunosorbent assay to polyclonal antibodies raised against the toxoid of their complex. PMID- 7779265 TI - A family systems nursing approach to hypertension. AB - This article focuses on a family systems nursing approach for essential hypertension. A case example is presented that describes the approach with a hypertensive woman with agoraphobia symptoms. A clinically significant decrease in the client's blood pressure occurred following the family sessions. Clinical observations of improved family relationships and symptom reduction corroborate research findings on the variables of perceived stress, anxiety levels and family coping resources. Interventions such as split-opinions, reframing, and rituals are described. PMID- 7779266 TI - PTCA: the role of the angioplasty program nurse. AB - Developing a program to provide continuity of care for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA) for coronary artery disease was the major task of the Angioplasty Program Nurse at the Sunnybrook Health Science Centre. To assist the patient and their family throughout the course of treatment and to offer strategies and resources for risk factor reduction required development of a patient assessment tool with clearly defined goals and objectives for documentation. Helping patients set realistic expectations in terms of procedural outcome and lifestyle modification is an important part of patient education and health promotion. Short hospital stays require good planning and comprehensive educational strategies in order to meet patient teaching outcomes. Evaluation is an important component of any program and having well defined goals and objectives with measurable outcomes aids the process. PMID- 7779267 TI - Patient outcomes research: Part II. PMID- 7779268 TI - Patient perceptions of the experience of electrophysiologic studies. AB - This descriptive study explored perceptions, feelings and attitudes related to electrophysiologic studies (EPS). Structured one hour taped interviews were conducted with 11 participants and data was subjected to qualitative analysis. Powerlessness, anticipation and total exhaustion were the categories identified from the data. Overall, participants generally perceived their EPS as a negative experience and illustrated this with words like invasion, horrible, uncomfortable, etc. Anxiety was predominant throughout the entire experience. Nurses are in an ideal position to impact these negative perceptions by helping patients incorporate the threatening nature of EPS into a cognitive plan, thus reducing anxiety. Strategies and interventions to help patients cope with this aversive event are offered as well as suggestions for future research. PMID- 7779269 TI - [Biologically active lignins from Magnolia biondii Pamp]. AB - Guided by PAF induced platelet aggregation, six active lignins were isolated from the flower buds of Magnolia biondii and identified as fargesin, demethoxyaschantin, aschantin, pinoresinol dimethyl ether, magnolin, lirioresinol B dimethyl ether. The 13CNMR and CD data were reported and the configurations were determined. PMID- 7779270 TI - [Chemical compositions of Podocarpus imbricatus]. AB - Twelve components were isolated from Podocar pus imbricatus, of which ten were identified as imbricatafiavone A (1), imbricataflavone B (2), robustaflavone (3), robustaflavone-7"-methyl ether (4), podocarpusflavone A (5), sandaracopimaric acid (6), beta-sitosterol (7), p-hydroxybenzoic acid (8), n-C34H69OH (9) and 10 nonacosanone (10). 4, 5, 8, 9 and 10 are obtained from the species for the first time. PMID- 7779271 TI - [Pharmacological studies of Polygonum capitatum Buch-Ham. ex D. Don]. AB - The pharmacological effect of aqueous extract of Polygonum capitatum has been studied. The experimental results show that Polygonum capitatum markedly decreases WBC and RBC in urine of pyelonephritis mode in rats, the death rate of Escherichia coli infected mice, and the temperature of feverish rabbits. It has also been found that after oral administration of Polygonum capitatum the animal urine markedly inhibits the growth of Escherichia coli, but diuretic action of the herb has not been observed. PMID- 7779272 TI - [A comparative study on the effect of absorbable components of several drugs on the growth and population doublings of rat diploid fibroblast]. AB - Embryonic skin fibroblast of Sprague-Dawley rats cultivated in vitro was used in this experiment. The cultural medium was added with absorbable components of several drugs. The result reveals that Yan Shou recipe, vitamin E and Huan Jing Jian have conspicuous promotive effect on the growth of diploid fibroblast and also help to increase population doublings. The experiment suggests that all these drugs possess anti-aging effect on the skin diploid fibroblast of rats. PMID- 7779273 TI - [Effects of isorhynchophylline on physiological characteristics of isolated guinea pig atrium]. AB - Isorhynchophylline (Iso) inhibits the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner, 30 mumol/L markedly depresses adrenaline-induced automaticity, 10 mumol/L prolongs functional refractory period and decreases excitability. Furthermore, 10 mumol/L of Iso reduces the effect of ouabain on contractile force in left atrium and 0.3 mmol/L markedly inhibits the response to paired stimulation. PMID- 7779274 TI - [Preliminary study on the anti-tubercular effect of Ottelia alismoides (L.) Pers]. AB - In clinical trials, the extract of Ottelia alismoides cured two cases of bilateral tuberculosis of cervical lymph gland within 3 months. The result of drug sensitive test showed that water extract of this herb could kill or inhibit human tubercular bacteria effectively, which suggests that Ottelia alismoides is a promising medicinal herb with anti-tubercular effect. PMID- 7779275 TI - [Review of constituents in fruits of Psoralea corylifolia L]. AB - Thirty-five constituents in the fruits of Psoralea corylifolia (identified since 1933) and their main physiological activities and clinical uses have been reviewed. PMID- 7779276 TI - [Identification on the botanical origin of xueshangyizhihao produced in Shaanxi, Gansu, Sichuan Provinces and Ningxia Hui Autonomous Region]. AB - The botanical origin of Xueshangyizhihao should be Aconitum brachypodum var. laxiflorum produced in Dongchuan, Huize and Xundian districts in Yunnan Province. Recently, this herb has been found coming from Shaanxi, Gansu, Sichuan Provinces and Ningxia Hui Autonomous Region. Botanical identification show that except the one from Sichuan being of the same origin as that from Yunnan, this herb consists essentially of the species of genus Aconitum, mainly A. flavum, A. pendulum, and others such as A. sungpanense, A. polyschistum and A. iudlowii. PMID- 7779277 TI - [High yield techniques for bupleurum falcatum L]. AB - The growth of plants may be controlled by clipping the aerial part. This may increase the yield of Bupleurum falcatum. Different methods of cultivation may result in different outputs of crude drugs. Compared with land plotting, deep ploughing and high ridging may increase the root weight of one-year-old plant by 28% and 50% respectively. PMID- 7779278 TI - [Influence of different processing methods of four alkaloid contents in Strychnos nux-vomica L]. AB - The contents of four alkaloids in different processed products of Strychnos nux vomica hamely, vomicine, icajine, strychnine N-oxide and brucine N-oxide, were determined by TLC-densitometry. The relationship between alkaloid contents and processing methods was studied. PMID- 7779279 TI - [Rectal administration of ash bark]. AB - A TLC-densitometric method was applied to determine aesculin in rabbit blood. The best way for ash bark rectal administration was found by orthogonal design [L4(2(3))]. The two routes of administration (per rectal, P.O.) were compared by bioavailabilities and the result indicated that per rectal was better than P.O. Modified isolated rectum-bag method was applied successfully to finding the best way for rectal administration of ash bark. PMID- 7779281 TI - [Stability of angesin solution]. AB - Chemical kinetics of ethyl acetate extract from the roots of Angelica sinensis in aguerus solution (angesin solution) was studied by isothermal acceleration test. The useful life (t0.9) calculated for angesin solution is one year. PMID- 7779280 TI - [Preparation method for compound Hirudo oral liquid]. AB - The extraction efficiency of alcohol, water and alcohol followed by water for Hirudo and the principal constituents of compound Hirudo oral liquid were compared with the extraction rate of nitric substances and pharmacological activity as the evaluation marker. Based on results of the above experiments, a new preparation method for the oral liquid was established. PMID- 7779282 TI - [Determination of psoralen and isopsoralen in tincture of fructus Psoraleae by HPLC]. AB - A reversed-phase HPLC method was described for the determination of psoralen and isopsoralen in tincture of Fructus Psoraleae. After adding the internal standard and diluting the sample to a definite volume, the sample was injected and analysed. The RSDs were within 2% and the minimum working concentrations below 1 microgram/ml; the average recoveries of psoralen and isopsoralen 102.8% and 99.5% respectively and the linear ranges of psoralen and isopsoralen 12-200 micrograms/ml and 13-210 micrograms/ml (r = 0.999) respectively. PMID- 7779283 TI - [Humoral immune response to the proteins of an antimeningococcal BC vaccine in a trial carried out in Antioquia, Colombia]. AB - This study evaluated the humoral response to protein components of the Cuban produced vaccine against serogroups B and C meningococcus, VA-MENGOC-BC, in adults and children 1 to 5 years old. The trial was conducted in an area of the Department of Antioquia, Colombia, in which an elevated incidence of meningococcal disease had been recorded. The serum anti-vaccine-protein response was studied before (T0) and after (T1) vaccination by means of enzyme-linked immunosorbent assay (ELISA), and lytic capacity was evaluated through the bactericidal antibodies test (BAT). The ELISA was performed before and after vaccination on the sera of 407 adults and 213 children. Lytic capacity against Cuban meningococcal strain B:4:P1.15 was studied with BAT in paired sera from 90 adults and 114 children. The two techniques showed a statistically significant response (P < 0.01) to the vaccine, in both adults and children. Of the total number of subjects tested with ELISA, 81% showed an immune response to the vaccine (T1/T0 > or = 2) (95% confidence interval, CI95%: 78% to 84%); among children, immune response was 91% (CI95%: 87% to 94%). All the children 1 year of age (n = 7) responded. Seroconversion (T1/T0 > or = 4), as shown by ELISA, was 80% among adults (CI95%: 73% to 86%) and 90% among children (CI95%: 83% to 100%). BAT demonstrated seroconversion in 85% (CI95%: 78% to 92%) of subjects who had been seronegative before vaccination, 85% of the adults (CI95%: 76% to 95%) and 84% of the children (CI95%: 72% to 96%). Seroconversion among children 3 and 4 years of age was 80%. The group of sera from children 1, 2, and 5 years old available for study with BAT was too small for meaningful statistical analysis; all of them seroconverted. In 20 sera chosen randomly for study of their bactericidal activity against all the strains isolated from patients in Colombia (B:4:P1.15, B:8:P1.nt, and two strains of serogroup C), seroconversion was found in all 20 cases. These results give reason to think that vaccination in this group produced an effective immune response, as measured serologically, and this belief is corroborated in practice by the lack of any cases of meningococcal disease through September 1994 among the people vaccinated. PMID- 7779284 TI - [Humoral immune response to the capsular polysaccharide of Neisseria meningitidis serogroup C in an antimeningococcal BC vaccination trial in Antioquia, Colombia]. AB - As a complement to studying humoral immune response to the proteins of an antimeningococcal vaccine (VA-MENGOC-BC) against serogroups B and C, the humoral immune response to polysaccharide C of the vaccine was also evaluated in 142 children from 1 to 5 years of age in an area of the Department of Antioquia, Colombia. Paired pre-(T0) and post-vaccination (T1) sera were tested for IgG response by means of ELISA and for serum lytic capacity against a strain of serogroup C by means of the bactericidal antibodies test (BAT). Response to the vaccine was statistically significant (P < 0.01) by both techniques. PAB demonstrated seroconversion (T1/T0 > or = 4) in 88% (95% confidence interval, CI95%: 80% to 95%) of all those who were seronegative before vaccination. The proportion of seroconversion in children 2, 3, and 4 years of age was 86% or more. Of all the sera tested with ELISA, 93% (CI95%: 89% to 97%) showed response to the vaccine (T1/T0 > or = 2), and 98% (CI95%: 94% to 100%) of the subjects with T0 < or = 500 U/mL seroconverted. In this sample, the vaccine stimulated a specific and protective response as measured by ELISA and BAT, the latter test being utilized to evaluate protection status. PMID- 7779285 TI - [Bactericidal effect of hydrated lime in aqueous solution]. AB - This study determined the bactericidal effect of the supernatants of saturated solutions of common lime and of micronized calcium hydroxide (Ca(OH)2) (1500 mg/L), which was used as a control, compared with disinfectants made of solutions of 0.33% colloidal silver (0.0016 mg/L), toluene sulfachloramine (41 mg/L) with sodium bicarbonate (9 mg/L), and sodium hypochlorite (5 mg/L). The test involved four strains of Vibrio cholerae 01, V. parahaemolyticus, Escherichia coli, Salmonella typhimurium, Shigella flexneri, Sh. sonnei, and Sa. enterititidis. These bacteria were inoculated into the bactericidal substances listed above and, after different incubation times, the number of surviving bacteria was determined in vitro by using a counting plate. The results were expressed in colony-forming units (CFU). An in situ estimate was made of the amount of V. cholerae on 35 strawberries and 35 radishes (having a weight of about 10 g per unit) after they were washed under a flow of potable water, submerged in the supernatant of the saturated lime solution (1.5 g/L), or both. The greatest bactericidal effect was obtained against V. cholerae 01 and was observed in 3 minutes. Other enterobacteria were resistant to the effect for up to 30 minutes. PMID- 7779286 TI - Kinetics: our window into the goals and strategies of the central nervous system. AB - The goal of this chapter is to demonstrate the role of integrated biomechanical analyses in complex movements such as gait in alerting researchers of the goals and synergies of the CNS. Because of the large number of segments involved and the potential for the CNS to take advantage of inter-limb coupling it is only through appropriate biomechanical analyses that such collaboration can be identified. Examples from normal, perturbed, elderly and pathological gait are presented to demonstrate the principles of total limb and total body analysis to pinpoint the goals of the CNS and to identify total limb or body synergies and adaptations in the elderly and in gait pathologies. Such findings reinforce the generalizations made many years ago by Bernstein [2] when he postulated several simplifying principles of CNS control. Also, evident from these analyses are the precision and accuracy of biomechanical variables that make these measures particularly sensitive to small changes within an individual or across a population group. PMID- 7779287 TI - Electrically evoked behaviors: axons and synapses mapped with collision tests. AB - The properties of many axon bundles mediating electrically evoked responses have been described using double-pulse methods in behaving animals. The directly stimulated axons whose activation leads to the behavior are defined by their refractory periods, conduction velocities and trajectories in those studies. In this review, new collision effects (asymmetric collision) are described that locate synapses mediating turning and startle responses. The direction, time and reliability of transmission are determined by the direction, time and strength of the asymmetry. In systems mediating turning, five axon bundles have been localized with symmetric collision effects and evidence for two synapses has been provided with asymmetric collision effects. In systems mediating startle responses, three fast, reliable synapses have been located with asymmetric collision. Asymmetric collision effects between a loud acoustic stimulus and a single electrical pulse in hindbrain sites define the timing and location of the acoustic volley that produces acoustic startle. Therefore, when synapses are strong, circuit diagrams can be constructed by use of collision tests in behaving animals. PMID- 7779288 TI - Stress-induced behavioral responses and multiple opioid systems in the brain. AB - Various stressor produce a wide range of behavioral responses such as analgesia, catalepsy and motor suppression, which are sensitive to opioid receptor antagonists. These behavioral responses in stress are accompanied by changes in the contents of opioid peptides, the mRNAs encoding their precursors and opioid receptor binding in the brain. In the present article, experimental data concerning stress-induced analgesia and motor suppression is reviewed and discussed in relation to a possible involvement of different opioid systems in the various observed behavioral responses in stress. Pharmacological studies with subtype-selective antagonists have demonstrated that not only mu- but also delta- and/or kappa-opioid receptors are involved in opioid-mediated stress-induced analgesia. There are two types of stress-induced analgesia referred to as opioid mediated and non-opioid mediated forms. It has been proposed that the intensity and temporal pattern of stressor may be a critical factor determining the nature of stress-induced analgesia. Accumulated evidence demonstrate that these two forms of pain inhibitory systems interact each other according to a collateral inhibition model. Recent studies show that parallel activation of multiple opioid receptors mediates non-opioid froms of stress-induced analgesia. Dynorphins, by acting at kappa-opioid receptors, may play a pivotal role in the expression of stress-induced motor suppression, whereas enkephalins may act to attenuate this response. PMID- 7779289 TI - The dorsomedial frontal cortex: eye and forelimb fields. AB - This review yields three conclusions: first, the eye field as described using unit recording and electrical stimulation on behaving monkeys trained to fixate visual targets is much larger than the 4 mm2 area originally described. Second, the eye field and forelimb field share a similar neural space within the dorsomedial frontal cortex (DMFC); thus the electrophysiogical studies that have been conducted on visually guided and sensory-triggered forelimb movements must be re-evaluated, since none of these studies controlled eye movement and eye position independently. Third, a topographic map representing eye position in orbit has been discovered in the DMFC; it is proposed that this topographic map records the order of positions of the eyes and forelimbs during the acquisition of visually guided movement sequences. PMID- 7779290 TI - The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour. AB - Cholinergic systems have been linked to cognitive processes such as attention, learning and mnemonic function. However, other neurotransmitter systems, such as the serotonergic one, which may have only minor effects on cognitive function on their own, interact with cholinergic function and their combined effects may have marked behavioural actions. Some studies have dealt with serotonergic-cholinergic interactions, but it is unclear whether both systems affect cognition directly or whether interactions at a behavioural level result from additional alterations in non-cognitive factors. This distinction is difficult, since it is possible that the diverse cholinergic and serotonergic systems serve different roles in the mediation of cognitive processes, both at the neuroanatomical and neurochemical level. Nevertheless, it is possible that cholinergic systems primarily alter accuracy in cognitive tasks, whereas serotonergic neurotransmission modulates behaviour by altering bias (motivation, motor processes). Whether serotonin alters accuracy or bias, however, may also depend on the cognitive process under investigation: it is suggested that attention, stimulus processing and/or arousal can be influenced by both cholinergic and serotonergic systems independently from each other. Cholinergic and serotonergic projections to cortex and thalamus may be of importance in the mediation of these cognitive processes. Serotonergic cholinergic interactions could also be of importance in the mediation of learning processes and trial-by-trial working memory. The data available do not allow an unambiguous conclusion about the role of these interactive processes in the mediation of long-term reference memory. These processes may rely on serotonergic cholinergic interactions at the hippocampal level. It is concluded that serotonergic-cholinergic interactions play an important role in the mediation of behavioural, including cognitive, performance, but that further studies are necessary in order to elucidate the exact nature of these interactions. PMID- 7779291 TI - Cerebellar contributions to cognition. AB - This review summarises the present evidence for the contribution of the cerebellum to cognition. While a data base from both animal and human clinical research supports the hypothesis of an important cerebellar role in motor adaptation, motor learning and timing, the evidence for the implication of the cerebellum in psychopathology and non-motor cognitive functions is incomplete and does not allow unequivocal conclusions. Methodological shortcomings and the lack of theoretical models on the nature of the cerebellar contribution to cognition limit the interpretation of the empirical studies available so far. PMID- 7779292 TI - Effects of short-term transcutaneous electrical nerve stimulation on memory and affective behaviour in patients with probable Alzheimer's disease. AB - The present study investigated whether a 30-minute-a-day transcutaneous electrical nerve stimulation (short-term TENS) might improve disturbances in memory and affective behaviour in patients with probable Alzheimer's disease. The hypothesis was derived from former studies in which beneficial effects on memory and affective behaviour of Alzheimer patients were found after a daily application of 6-h TENS and a 30-min tactile stimulation. The present data reveal that short-term TENS improved some aspects of verbal and visual short-term and long-term memory. Moreover, patients who had undergone this treatment felt, e.g., less dejected, less gloomy, less irritable, more cheerful, more active, and more alert. They were also more interested in social contacts and participated more in daily activities. After a period of 6 weeks following treatment, the effects on memory as well as the improvements in affective behaviour partially remained. PMID- 7779293 TI - Influence of prefeeding and scopolamine upon performance in a delayed matching-to position task. AB - The present study compared the influence of prefeeding (0, 10, 20 g or an unlimited amount of food pellets for a 90 min period prior to testing) with the effects of scopolamine (0, 0.03, 0.075 or 0.1 mg/kg s.c.) and scopolamine methylbromide (0.1 mg/kg s.c.) upon performance in the food reinforced delayed matching-to-position (DMTP) task. In preliminary studies using separate groups of rats, both scopolamine (but not scopolamine methylbromide) and prefeeding impaired choice accuracy in a seemingly delay-independent manner. Both treatments also increased omissions. However, while prefeeding increased all task latencies, scopolamine only increased sample latency. In a subsequent experiment, an intermediate dose of scopolamine (0.075 mg/kg s.c.) was directly compared with prefeeding in the same animals. Both treatments impaired choice accuracy, however, the effects of scopolamine were significantly larger than prefeeding. Conversely, prefeeding caused significantly greater omissions and larger increases in task latencies compared with scopolamine. These findings demonstrate some dissociation between the effects of scopolamine and prefeeding in the DMTP task, suggesting that the actions of scopolamine are not entirely due to reduction in motivation. Furthermore, the effects of scopolamine are likely to be centrally mediated. PMID- 7779294 TI - Distractibility and locomotor activity in rat following intra-collicular injection of a serotonin 1B-1D agonist. AB - The superior colliculus (SC) is thought to be the decision center for reactions to novel and/or moving stimuli in the peripheral visual field. Serotonin 1B (5 HT1B) receptors were previously demonstrated to be located on collicular axon terminals of retinal ganglion cells and their activation might depress afferent inputs from the retina. The effects of intra-collicular injections of 5-HT1 drugs on distractibility were studied in hooded rats trained to run toward illuminated targets for a food reward in a 2-choice runway. 8-hydroxy-2-(di-n propylamino)tetraline (8-OH-DPAT), a 5-HT1A receptor agonist, RU 24969, a mixed 5 HT1A and 5-HT1B agonist, serotonin-O-carboxymethylglycyltyrosinamide (S-CM GTNH2), a mixed 5-HT1B and 5-HT1D receptor agonist and saline (control) were alternately injected. Following the S-CM-GTNH2 treatment alone, animals exhibited an erratic running style, involving side-to-side movements of the head, without change in the overall accuracy of their locomotor trajectories, but with substantial decrease in their running speed. When distracting peripheral lights were introduced at the mid-points of the animals' run, in the weaker distracting condition (unilateral distractor) only, distraction indexes were found lower following the S-CM-GTNH2 treatment than following the other drug or saline treatments. It is concluded that serotonin, via 5-HT1B-1D receptors, may induce an elevation of the visual distractibility threshold by modulating directly the transmission of the primary visual signal. PMID- 7779295 TI - Attention and memory trials during neuronal recording from the primate pulvinar and posterior parietal cortex (area PG). AB - Cynomolgus monkeys were trained on a delayed match-to-sample (DMS) task. Several controls were performed for the separation of memory effects from other factors such as attention, stimulus attributes and eye movements. One of the controls employed a standardised sequence of events ('window trial') during which a window in a black screen was opened and a face, an object or a picture was presented. Unit cell activity was recorded from 209 sites in the posterior parietal cortex (area PG) and 186 sites in the pulvinar. Some units responded during the presentation of the DMS stimuli, mostly those in that part of area PG located in the superior temporal sulcus. They often appeared to be related to the task related state of attention. There was no indication of pure memory-related changes in activity such as sustained responses during the inter-stimulus interval or specific responses to the second stimulus that would indicate a dependence on the kind of the preceding stimulus. In the window trial, some parietal units, mostly in that part of area PG located in the intraparietal sulcus (a region termed area LIP), responded in a relatively specific manner during and sometimes even after, the presentation of a human face. The responses often seemed to be related to the animal's state of attention. Almost no pulvinar unit responded in this paradigm. It is concluded that area PG and, to a lesser extent, the pulvinar are involved in the modulation of attention in relation to behaviourally relevant changes in the environment. If these structures have a role in memory function, it must be secondary to a role in controlling or regulating attention. PMID- 7779297 TI - Molecular dynamics simulation of anesthetic-phospholipid bilayer interactions. AB - To probe the hypothesis of a lipid-mediated mechanism of general anesthetic action on a molecular level, and to help elucidate the nature of the interactions of bioactive compounds with membranes, the effects of trichloroethylene (TCE), an inhalational general anesthetic, on a dioleoylphosphatidylcholine (DOPC) lipid bilayer have been investigated by molecular dynamics (MD) simulations at 37 degrees C and 1 atm and the results compared with 31P and 2H NMR experimental studies (Ref 1). The model used included a single TCE molecule embedded in a lipid bilayer consisting of 24 DOPC molecules and an 8 A layer of explicit water of solvation in each polar head group region of the bilayer, together with constant-pressure periodic boundary conditions in three dimensions. A comparison of the bilayer properties calculated in the presence and absence of the anesthetic led to the detection of three major perturbations of the bilayer caused by the anesthetic at 1 atm: i) an increase in the ratio of the effective areas of hydrocarbon tails and the head group per lipid, predicting the tendency of lipids near the anesthetic site of action to form a hexagonal phase (HII); ii) a slight increase in the frequency of chain dihedral angles found in the gauche conformation; and iii) a significant increase in the lateral mean-square displacement of lipid molecules, an indication of increased lipid lateral diffusion and membrane fluidity. The pressure antagonism of these effects was also studied by MD simulations at pressures of 200 and 400 atm. The study of the pressure reversibility of these effects at 200 and 400 atm indicated that they were partially prevented at 200 atm and essentially blocked at 400 atm, suggesting their probable relevance to the pressure reversal effect seen with general anesthesia. These results may thus provide insights into the interaction between general anesthetics and similar small organic molecules with membranes. PMID- 7779296 TI - Low-dose challenge by the NMDA receptor antagonist dizocilpine exacerbates the spatial learning deficit in entorhinal cortex-lesioned rats. AB - We investigated the effects of a bilateral quinolinic acid lesion of the medial entorhinal cortex (EC) on acquisition of a spatial learning task. During reversal of the same task, we challenged the animals by the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801). Training took postoperatively place in an eight-arm radial maze in which four of eight arms were baited. In the acquisition phase (ten blocks of five trials) of the test, EC-lesioned animals showed a working (WM) and a reference memory (RM) deficit. The WM deficit was prominent at the beginning and fully compensated at the end of the acquisition phase. The RM deficit became more evident during the course of the experiment. In the reversal learning phase (seven blocks of five trials), the formerly unbaited arms were baited and half of the control and lesioned animals were challenged by a low dose of dizocilpine (0.04 mg/kg i.p.) before training. Only lesioned and additionally dizocilpine-treated animals showed a WM deficit that was again compensated and a RM deficit that was stronger at the end of the test. In summary, quinolinic acid lesion of the medial EC induces both WM and RM deficits in rats. The WM deficit is rapidly compensated. Enhancement of these deficits by challenge with dizocilpine in the reversal learning phase suggests that the NMDA receptor system was rendered more sensitive by this type of lesion. PMID- 7779298 TI - Conformational properties of the Arg-Leu-Gly tripeptide--DMSO--water clusters with the combined use of molecular dynamics and energy minimization studies. AB - The Arg-Leu-Gly tripeptide is the repeating fragment of sequential arginine-rich polypeptides capable of interacting with DNA. The conformational influence of solvent molecules (DMSO/H2O) were investigated with the combined use of molecular dynamics and energy minimization. It was found that water molecules greatly contribute to the peptide structure by solvating all its hydrophylic sites even in the presence of DMSO excess, whereas one water molecule links the ammonium and carboxylic ends of the Arg-Leu-Gly. The persistence of residual water, which was confirmed by varying the computer simulation parameters, indicates that pretreatment of peptide segments in aqueous solutions should greatly affect their conformational properties in organic media. A satisfactory agreement between experimental data (1H-NMR and IR spectroscopy) and the presented computational study deserves also to be noted. PMID- 7779299 TI - Mathematical modelling of electrostatic fluctuations in subtilisin active site. AB - The intensities of electrostatic fluctuations in subtilisin active site generated by conformational motion of charged side chains, polar side chains and peptide bonds of the main chain are calculated. The comparative analysis of all these fragments reveals that there are few of them which make the main contribution to the total value of the intensity, which has been found to be approximately 10(7) g.cm-1.s-2. These are Ser 125, Thr 220 and peptide bonds of aminoacids 125-126, 218-219. Our present analysis enables us to compare the relative contribution of different fragments but we do not pretend to obtain precise absolute values. The reason for this is the lack of the detailed selective information on the mean square amplitudes and correlation times of conformational motion of the fragments and on the values of local dielectric constants in the interior of subtilisin. The possibility for electrostatic fluctuations in enzyme active site to be an efficient nonspecific source of substrate activation is discussed. PMID- 7779300 TI - A statistical analytical approach to decipher information from biological sequences: application to murine splice-site analysis and prediction. AB - A simple statistical approach for the analysis of biological sequences, such as splice-sites, promoter regions, helices and extended structure forming regions or any other sequence dependent functional entities in proteins, is presented. The approach has been proved useful to develop a method for prediction of such entities in newly available sequences. We first search for invariant sequence features of each functional entity from the experimentally available sequences and identify a set of 'like' sequences with similar sequence features. In the next step, concrete features of sequence entities in terms of occurrences of smaller subsequences are identified at various positions which are used as a knowledge base to select potential functional entities from the identified 'like' sequences. The third step consists of refinement of this pattern learning, statistical improvements of the knowledge base weight matrices, and finally its application to predict functional entities in newly available sequences. Such an analysis is operationally described for murine splice-site predictions. Regions comprising -30 to +30 nucleotides from the splice-junction at the murine splice sites (donors and acceptors), reported earlier, were analyzed. Invariant sequence specific features in terms of monomer frequency average were used to identify splice-site-like sequences in the EMBL murine DNA sequence data base. The frequencies of occurrence of mono-, di-, tri- and tetranucleotides in the known splice-sites were studied in comparison with the splice-site-like sequences; the significant differences in their occurrences were extracted as statistical knowledge coded in weight matrices for computer to identify potential splice sites. The algorithm was refined and a method was developed to predict potential splice-sites in a given murine DNA; the analysis was also extended to human DNA. The success rate of the method to predict correct splice-sites in these species is found to be 80% and 85%, respectively. The major strength of this method lies in reducing significantly the number of false positives which are normally picked up in such analysis. PMID- 7779301 TI - Solution structure of a selectively 13C-labeled intramolecular DNA triplex. AB - The three-dimensional structure of an intramolecular triple helix whose three strands have been linked by a hexaethylene glycol chain, and selectively 13C enriched in position C1' on the third strand was investigated by NMR spectroscopy and constrained molecular mechanics calculations. Starting from different initial conformations, we show that the NOE constraints determined by the complete relaxation matrix calculation and iterative back-calculations allowed us to reach the same final restrained triple helix, taking into account implicitly the solvent effect. We conclude that this triplex adopted a B-type conformation rather than a A-type. The sugar pucker was found predominantly in the S-type conformation, in the range of C2'-endo geometry. PMID- 7779302 TI - Chirality and surface twist of DNA wrapped on protein surfaces. AB - The surface twist, STw, is a measure of the component of duplex twist associated with the trajectory of the DNA axis wrapped on a protein surface. We calculate STw for various surfaces of revolution, including the cylinder and truncated paraboloid, ellipsoid, and hyperboloid of revolution. We show that the sign of STw cannot be stated unequivocally from knowledge of the chirality of the wrapping but depends also upon the nature of the wrapping (protein) surface. We define and discuss three geometric classes. Class (1) includes the cylinder, certain types of convex paraboloids, all concave paraboloids, the prolate ellipsoid, and the hyperboloid; here STw > 0 for right-handed wrapping and STw < 0 for left-handed wrapping. Class (2) is the sphere, for which STw = 0 for both types of handedness. Case (3) includes oblate ellipsoids and some regions of convex paraboloids; here STw < 0 for right handed wrapping and STw > 0 for left handed wrapping. PMID- 7779303 TI - Interaction with DNA of photoactive viologens based on the 6-(2- pyridinium)phenanthridinium structure. AB - A new type of DNA-interacting violgens derived from the N,N'-dialkyl 6-(2 pyridinium)-phenanthridinium structure (in which dialkyl is -CH2CH2-,-CH2CH2CH2-, or (-CH3)2) have been synthesized. Electronic spectroscopy, steady-state and time resolved fluorescence, cyclic voltammetry, binding isotherms, viscosity titrations, and molecular modeling techniques were employed to characterize the structural, photophysical and redox properties of the novel drugs as well as the corresponding drug-DNA complexes. The viologens display significant visible absorption (up to ca. 490 nm), and a rather intense luminescence (phi cm from 0.06 to 0.20 at 491-565 nm wavelength maxima) which is efficiently quenched by DNA. The calculated redox potentials of these drugs in their singlet excited state (+2.1 V vs. SHE) predict a large driving force for a photoelectron transfer reaction from the nucleobases to the drugs. Photochemical measurements of the viologens in the presence of mononucleotides, nucleosides, and deoxyribose indicate that the observed fluorescence quenching occurs indeed by electron transfer from the DNA bases rather than the sugar phosphate backbone. Large association constants to double helical DNA (in the order of 10(5) M-1) have been evaluated from the absorbance-based binding isotherms. Viscosimetry supports intercalation of the drugs into the DNA helix. Computer simulations (molecular mechanics of d(CGCGCG)2-drug complexes) confirm the intercalative nature of the binding and provide finer details about the geometry of the different viologen DNA complexes. Molecular modeling has also revealed a stereoselective interaction of the enantiomeric drug conformers with the chiral DNA helix. A DNA-targeted drug design of future generations of these ligands in order to improve and/or modulate their photochemical, redox, and nucleic acid binding properties appears to be possible by a careful selection of the N,N'-dialkylating chain and/or the substituents on the azaheterocyclic moieties. PMID- 7779304 TI - DNA interaction of the imidazole-containing lexitropsin ImPy: titration viscometric study in comparison to netropsin. AB - The imidazole (Im) containing lexitropsin ImPy related to netropsin (Nt) is a sequence reading DNA ligand which, in contrast to Nt, permits binding to a GC base pair. The ImPy induced DNA conformational changes differ significantly from those induced by Nt as monitored by titration viscometry, although interaction modes have also been resolved with boundaries at the same ligand to DNA phosphate ratio, r. Evidently ImPy covers similar binding sites (in the same sequence) as Nt for natural calf thymus DNA at r < 0.023. This result suggests that the preferred binding sites of ImPy are A tracts (cf. K.E.R. JBSD 9(1993) 973), in agreement with previous data. The respective DNA coil expansion, most probably caused by unbending (l.c.), is similar but smaller compared to the Nt-DNA interaction. These results again suggest that, at low r values, the van der Waals interaction in the narrowed minor groove of AT clusters provides a dominating energy contribution to ImPy binding. At r > 0.03 the DNA coil expansion increases to extremely high values in that r range where Nt binding (to mixed AT/GC sequences) induces no effect at all owing to steric hindrance with the amino group of guanine. On the basis of many quantitative results for the Nt-DNA systems these effects can be understood in terms of an unbending of intrinsic helix bends (l.c.). They are of considerable interest in connection with the ability of such compounds to influence the direction of the local regulatory relevant DNA curvature. PMID- 7779305 TI - Comparison of different footprinting methodologies for detecting binding sites for a small ligand on DNA. AB - In order to assess the utility of different methods of footprinting applied to the study of sequence-selective small molecule-DNA interaction we have performed a homologous series of experiments on the binding of echinomycin, a bis intercalator, to a 133 base pair DNA restriction fragment containing a small number of discrete binding sites. Two of those sites each contained a pair of closely clustered CpG steps, the cognate dinucleotide sequence which is the common denominator of sites recognised by echinomycin. DNAse I was found to be much the best enzyme for footprinting in terms of sensitivity, accuracy, and ease of handling. DNAase II and micrococcal nuclease were of limited value. Excellent results were recorded with methidiumpropyl-EDTA.FeII which picked up strong binding sites and yielded sharp footprints from which a parsimonious estimate of site size could be determined. Orthophenanthroline.CuI proved to be a very suitable, sensitive chemical nuclease but hydroxyl radical footprinting with EDTA.FeII was only partially successful. Positive footprinting with conformation sensitive probes diethylpyrocarbonate, osmium tetroxide and potassium permanganate yielded information to complement that afforded by the enzymic and chemical nucleases. Evidence of binding to both CpG steps in the clustered pair was obtained, with indications of possible cooperativity. PMID- 7779306 TI - Distortion after monofunctional alkylation by mitomycin C of a dodecamer containing its major binding site. AB - The structural distortions of the duplex dodecamer d(ATTAACGTTAAT)2 monofunctionally alkylated by mitomycin C have been studied by the use of chemical probes reactivity and resonance Raman spectroscopy. This sequence contains the 5'-ACGT sequence for which mitomycin C was determined to present the best affinity (S. Kumar, R. Lipman, and M. Tomasz, Biochemistry 31, 1399 (1992)). Raman spectroscopy as well as osmium tetroxyde reactivity indicate that the distortion of the double helix structure is located around the central CG bases. Mitomycin C reacts exclusively with the 2-amino group of guanine and this binding does not disrupt the inter bases H-bonds, as indicated by chloroacetaldehyde reactivity. Although resonance Raman spectroscopy does not allow the handedness of the monoalkylated CG/GC sequence to be determined, it indicates a similarity between the base stacking and that which would be observed for alternating purine/pyrimidine sequences at high salt concentration. PMID- 7779307 TI - Molecular dynamics simulations of chlorambucil/DNA adducts. A structural basis for the 5'-GNC interstrand DNA crosslink formed by nitrogen mustards. AB - The alkylation of DNA by chlorambucil has been studied using a computational approach. Molecular dynamics simulations were performed on the fully solvated non covalent complex, two monoadducts and a crosslinked diadduct of chlorambucil with the d(CGG3G2CGC).-d(GCG1CCCG) duplex, in which the N7 atoms of G1, G2 and G3 are potential alkylation sites. The results provide a structural basis for the preference of nitrogen mustards to crosslink DNA duplexes at a 5'-GNC site (a 1,3 crosslink, G1-G3) rather than at a 5'-GC sites (a 1,2 crosslink, G1-G2). In the non-covalent complex simulation the drug reoriented from a non-interstrand crosslinking location to a position favorable for G1-G3 diadduct formation. It proved possible to construct a G1-G3 diadduct from a structure from the non covalent simulation, and continue the molecular dynamics calculation without further disruption of the DNA structure. A crosslinked diadduct developed with four BII conformations on the 3' side of each alkylated guanine and of their respective complementary cytosine. In the first monoadduct simulation the starting point was the same DNA conformation used in the crosslinked diadduct simulation with alkylation at G1. In this simulation the DNA deformation was reduced, with the helix returning to a more canonical form. A second monoadduct simulation was started from a canonical DNA conformation alkylated at G3. Here, no significant motion towards a potential crosslinking conformation occurred. Collectively, the results suggest that crosslink formation is dependent upon the drug orientation prior to alkylation and the required deformation of the DNA to permit 1,3 crosslinking can largely be achieved in the non-covalent complex. PMID- 7779308 TI - Predictors of fear of falling in dizzy and nondizzy elderly. AB - Fear of falling may constitute an independent risk factor for disability, leading older people to unnecessarily restrict their activity. Sixty older adults with chronic dizziness and 66 healthy controls were studied to help clarify the interrelationships among demographic factors, psychological status, physical health, and fear of falling. Chronic dizziness was strongly associated with fear of falling; among dizzy patients, nearly half (47%) expressed fear of falling, in comparison with 3% of controls. In participants with dizziness, 3 factors predicted fear of falling: an activity of daily living score, the revised Symptom Checklist 90 Depression (Derogatis, 1983) score, and stability when standing with feet together. These results support the concept that fear of falling is multiply determined and that psychological factors play a major role in influencing the symptoms and responses in many older patients with dizziness. PMID- 7779309 TI - Age differences in conversational source monitoring. AB - The present investigation simulated a group conversation in which participants asked (inquirer) and answered (responder) questions, as well as listened to others exchange information. Source (inquirer; responder) identification accuracy was evaluated immediately or after 1 week. Older adults were less adept at source identification, although this difference was reduced with personal (Experiment 2) rather than categorical (Experiment 1) topics. The age difference was independent of explicit memory (cued recall and recognition), suggesting that memory for source and information are separable. Older adults were comparable to younger adults in responder identification but worse at inquirer identification. Responder identification was better than inquirer identification, with the latter dropping to chance at 1 week. Source identification was most accurate when participants were in the responder role; there was little difference between the inquirer and listener roles. PMID- 7779310 TI - Adult life span changes in immediate visual memory and verbal intelligence. AB - A sample of 558 women and 1,163 men 17 to 102 years old, screened for neurodegenerative and neuropsychiatric disease, was administered tests of immediate visual memory (Benton Visual Retention Test) and crystallized intelligence (Wechsler Adult Intelligence Scale Vocabulary subtest) from 1 to 5 times over 27.7 years. Cross-sectional and longitudinal evidence led to the conclusion that the 65-74-year decade was a watershed for decremental changes in immediate visual memory and verbal intelligence. Age accounted for considerably less variance in vocabulary than in immediate memory. The proportion of individuals whose longitudinal trajectories were contrary to group trends decreased substantially with increased age; observed age changes remained when analyses were restricted to individuals who had perfect or near-perfect mental status scores. Selected neuronal loss and slower reproduction times were considered as possible causes. PMID- 7779311 TI - Emotional behavior in long-term marriage. AB - In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages. PMID- 7779312 TI - Realization of generativity in two samples of women at midlife. AB - On the basis of E. H. Erikson's (1950/1963) theory of midlife development, a measure of generativity realization was constructed with items from J. Block's (1961/1978) California Adult Q-Set (CAQ). Convergent and discriminant validity for the new CAQ measure were established through a survey of 2 samples of educated women at about 43 years of age (N = 208). These 2 samples, 1 from a study of Mills College graduates and the other from a study of Radcliffe College graduates, were also used to examine the personality, attitudinal, and life outcome correlates of generativity at midlife. Results indicated that generative women have prosocial personality characteristics, express generative attitudes through their work, are invested in the parenting process, and exhibit an expanded radius of care. In general, results conceptually replicated in the Mills and Radcliffe samples. PMID- 7779313 TI - Playing with pets and longevity among older people. AB - Models of the relations between contact with pets and better health are examined in an archival prospective study using data derived from the longitudinal study initiated by Terman in 1921 (current N = 343 men, 300 women). In survival analyses of documented longevity, playing with pets in 1977 (M age = 67 years) was not associated with mortality risk through 1991 for the total sample nor for those who were unmarried or those who were less satisfied with their human relationships. Playing with pets was not associated with health-prone attributes or healthy behaviors such as personality, social ties, education, and smoking. PMID- 7779314 TI - Cognition and depression in a cohort of aging men: results from the Western Collaborative Group Study. AB - Relationships between cognitive performance and self-ratings of depression on the Center for Epidemiologic Studies Depression scale (CES-D; L.S. Radloff, 1977) were examined for 1,217 older men. After controlling for demographic variables and both objective and subjective measures of health, significant associations were observed between several CES-D variables and measures of cognitive mental status, memory, and psychomotor speed. The Well-Being factor of the CES-D was the most robust predictor of cognitive scores. Therefore, for older adults with generally favorable health and socioeconomic resources, there may be a link between positive affect and maintenance of cognitive effectiveness. PMID- 7779315 TI - Aging and negative priming in a location suppression task: the long and the short of it. AB - The role of temporal parameters in aging and inhibitory function was examined using negative priming (NP) and repetition priming (RP) in a task involving a series of visually presented prime-probe sets; responses were made on the basis of the location of a target stimulus. Preparatory intervals (PI) preceding prime probe sets were 3,000 ms or 1,500 ms. The longer PI resulted in less NP in older adults than did the shorter PI. Further analysis suggest that older adults may be less prepared to inhibit the distractor following the longer PI. The longer PI also produced more RP than did the shorter PI for both age groups, indicating a greater emphasis on facilitatory processes in this condition. In addition, evidence was obtained to suggest that an inverse relationship between NP and RP exists for both young and old adults. These data suggest that individuals or task conditions may emphasize either facilitation or inhibition in selection. PMID- 7779317 TI - Sleep compression and sleep education for older insomniacs: self-help versus therapist guidance. AB - A treatment package consisting of a bed-time restriction strategy and education was administered to 50 insomniacs and 50 noninsomniacs 60 years or older. Half of the insomniacs and noninsomniacs received treatment through a self-help video only, whereas the remaining treated participants received therapist guidance to supplement the video. A waiting-list control group of 25 senior insomniacs was also included. Sleep knowledge was equivalent for senior insomniacs and noninsomniacs. The self-help insomniac group exhibited improvement on multiple sleep variables, but the addition of therapist guidance appeared to enhance treatment outcome for sleep latency, wake time after sleep onset, and sleep satisfaction. Control participants also improved across time but were generally outperformed by treated insomniacs. PMID- 7779318 TI - A comparison of coping strategies of aging mothers of adults with mental illness or mental retardation. AB - Differences in coping by 105 aging mothers of adults with mental illness and 389 similar mothers of adults with mental retardation were investigated. Although no differences in problem-focused coping were found, mothers of adults with mental illness used more emotion-focused coping, which predicted greater maternal depression. For mothers of adults with retardation, depressive symptoms were a function of their child's behavior problems, although this source of stress was buffered by coping. For mothers of adults with mental illness, depression was a function of caregiving demands, but coping did not buffer the effects of stress. Explanations for findings include maternal perceptions of the context of care, of her control over the disability, and her caregiving efficacy. PMID- 7779319 TI - Predictors of planned retirement age: an application of Beehr's model. AB - Given the aging workforce, understanding the retirement process is an area of increasing interest to organizations. T. A. Beehr's (1986) model of retirement behavior was used in this study as a basis for selecting personal, psychological, and organizational predictors of subsequent planned retirement age. In addition, potential differences in predictors of the planned retirement age of retirement eligible and retirement-ineligible respondents were explored. Two hundred sixty four respondents working for a large multinational firm completed 2 surveys on their attitudes toward work and retirement. Results showed that chronological age, employee health, and self-perceptions of the ability to adjust to retirement predicted subsequent planned retirement age. Interactions of the predictors with retirement eligibility are reported along with implications for retirement planning programs. PMID- 7779316 TI - Genetic mediation in the relationship of education to cognitive function in older people. AB - We used data from 136 monozygotic and 125 dizygotic human, male twin pairs (M age = 64 years, range = 59 to 70 years) to test whether the previously observed association (r = .30, p < .01) between cognitive performance and education in this sample is genetically mediated. Biometric genetic modeling found that a common genetic latent variable accounted for 44% of the total variance in the Mini-Mental State Exam (MMSE: M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975), 40% of the variance in the Iowa Screening Battery for Mental Decline (P. J. Eslinger, A. R. Damasio, & A. L. Benton, 1984), and 21% of the variance in educational attainment. In addition, specific genetic and environmental variables contributed significantly to individual differences in education and cognitive performance of the participants. PMID- 7779320 TI - Generalized slowing in sinusoidal tracking by older adults. AB - Older and younger adults manually tracked sinusoidal input signals. Older adults exhibited 2 forms of slowing. First, they lagged behind the target somewhat more than younger adults. Second, they made considerably smaller movements than the younger adults. Because the velocity of a sinusoidal pattern is proportional to its amplitude, these smaller movements were also slower. Both older and younger adults made smaller movements with a compensatory display and with higher frequency inputs. The high degree of proportionality among these effects was taken as evidence for generalized slowing by the older adults. This slowing may prevent older adults from successfully adjusting an internal pattern generator to match their motions to the sinusoidal input signal. PMID- 7779321 TI - Discourse comprehension and problem solving: decisions about the treatment of breast cancer by women across the life span. AB - The 1st study examined the decision making and prose comprehension of 94 women interacting with an authentic, unfolding health scenario about breast cancer. The 2nd study involved questionnaire data focusing on the decisions made by 75 women who had been diagnosed with breast cancer. Two major findings emerged from this laboratory and survey research. First, older women sought less information when making treatment decisions about breast cancer. However, the outcome of those decisions were equivalent to those of younger women. Second, older women made these decisions faster than younger women. In addition, treatment decisions were related to prose processing, the type of information underlined as important while reading as well as the type of information remembered about various treatment options. PMID- 7779322 TI - Bis(acetato)amminedichloro(cyclohexylamine)platinum(IV), an orally active anticancer drug. AB - The structure of the anticancer drug bis(acetato) amminedichloro(cyclohexylamine)platinum(IV), [PtCl2-(C2H3O2)2(C6H13N)(NH3)], is reported. The acetato groups are axial to the square plane composed of the chlorine and amine substituents. The cyclohexane ring may sterically hinder one of the acetato groups for metabolic attack. The amine groups are hydrogen bonded to the carbonyl O atoms of the acetato groups. PMID- 7779323 TI - (2,3,7,8,12,13,17,18-Octaethylporphinato)perchloratomanganese(III). AB - The crystal structure of [Mn(OEP)(OClO3)] (where OEP = C36H44N4) has been determined. The axial Mn-O bond length is 2.183 (2) A and the equatorial Mn-Np bond lengths have an average value of 2.000 (5) A. The molecules form weak dimers in the solid state with interring distances of 3.49 A and a lateral shift of 3.27 A. The compound is found to be isomorphous with the iron derivative [Fe(OEP)(OClO3)]. A brief comparison of the structural parameters for the two molecules is given. PMID- 7779324 TI - KR-25003, a potent analgesic capsaicinoid. AB - The crystal structure of N-[3-(3,4-dimethylphenyl)propyl] (4-hydroxy-3 methoxyphenyl)acetamide, C20H25NO3, was determined to a final R value of 0.047. The vanilloid, amide and dimethylphenyl groups of the compound are nearly perpendicular with respect to one another. The overall conformation in the crystalline state is somewhat different from that of other capsaicinoids. The molecules are stabilized by intermolecular hydrogen bonds. PMID- 7779325 TI - 8-Acid derivative of the antitumour agent mitozolomide. AB - The crystal structure of 3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1 d][1,2,3,5]tetra zine-8- carboxylic acid, C7H6CIN5O3, a derivative of the novel bicyclic antitumour agent mitozolomide, 3-(2-chloroethyl)-3,4-dihydro-4 oxoimidazo[5,1-d][1,2,3,5]tetra zine-8- carboxamide, has been determined at 293 K. The expected dimer, hydrogen bonded via the two carboxyl groups, does not occur. In preference, the two molecules in the asymmetric unit utilize hydrogen bonding between the carboxyl group of one and the N atom and CH in the imidazo ring of the other. These two then further interact via the same scheme with their centrosymmetrically related pair to produce a fully hydrogen-bonded planar tetramer. PMID- 7779326 TI - Methyl (2S,6S:2R,6R)-6-(2-cyanoethyl)-4,6-dimethyl-2-morpholineacetate. AB - The morpholine ring of the title compound, C12H20N2O3, adopts a chair conformation with an equatorial (methoxycarbonyl)methyl group. The cyanoethyl and (methoxycarbonyl)methyl groups are trans with respect to each other. The global minimum conformation, as computed by PCMODEL [Gajewski & Gilbert (1992). Molecular Modeling Package. Version 4.0], of the title compound agrees with that observed in the crystal. In the crystal, the torsion angles (N identical to)C-CH2 CH2-C(O), (N identical to C)CH2-CH2-C-O, O-CH-CH2-C(OOCH3) and (O)CH-CH2-C(O) O(CH3) have values -170.0 (1), -45.9 (2), -71.6 (2) and 142.8 (1) degrees, respectively. PMID- 7779327 TI - X-ray microscopy. AB - The subject of X-ray microscopy (high-resolution X-ray imaging of general nonperiodic structures), an area in which much progress has been made in recent years, is reviewed. The main techniques are briefly described. Achievable performance levels, which for many years were highly speculative, can now be understood with fair accuracy in terms of basic X-ray and specimen properties, and techniques have progressed to the point where actual results are nearing those levels. In terms of specimen size and imaging resolution, X-ray microscopies lie between electron and light microscopy, and are thus suited to imaging extremely large and complex structures; in addition, they demand little or no specimen preparation, and can be used to observe local composition and chemical state as well as structure. Thus X-rays, which have played the leading role in imaging crystallizable materials, may also prove to be highly valuable in the imaging of very large non-crystalline structures. Throughout the treatment, attention is paid to the relationships connecting the subject with X-ray crystallography. PMID- 7779328 TI - Physiatry as a primary care specialty. AB - The ongoing changes in health care seek to create an affordable, accessible, and high-quality health care delivery system for all Americans. In response to this, Physical Medicine and Rehabilitation (PM&R) is re-examining its role in the provision of health care to the disabled, particularly the severely affected. We surveyed 100 physiatrists and 100 PM&R residents across the country regarding their opinions on the competence, qualifications, and desire of physiatrists to provide primary care for the disabled. Fifty-five physiatrists and 51 residents responded (55% overall). Thirty-nine percent of all respondents agreed that PM&R should be designated as a primary care specialty, and 53% believed that physiatrists should provide primary care to the severely disabled (e.g., spinal cord and head injury). Overall, 53% felt that physiatrists are competent in general medical care, but 38% are convinced that the current 4-yr PM&R residency training sufficiently prepares physiatrists to assume the role of a primary care provider. Of the patient populations considered, the respondents thought that physiatrists should manage the care of spinal cord injury (60%) and head injury (51%), but only 40% were willing to assume primary care responsibilities. PMID- 7779329 TI - Postoperative transcutaneous oxygen measurement in the prediction of delayed wound healing and prosthetic fitting among amputees during rehabilitation. A pilot study. AB - Postoperative assessment of amputation wound healing remains largely subjective in nature, being based on the physician's clinical judgement. These considerations significantly impact on the rehabilitation course, as premature prosthetic fitting may result in wound breakdown. Alternatively, delayed healing may result in prolonged hospital length of stay. Few attempts have been made to correlate objective parameters of limb perfusion with amputation wound healing or prosthetic fitting outcome during the rehabilitation phase of treatment. A pilot study was conducted, in which the transcutaneous oxygen monitor, a noninvasive device measuring transcutaneous partial pressure of oxygen (tcpO2), was applied to the stumps of 11 consecutive above-or below-knee amputees admitted for rehabilitation after amputation. All patients were tested within 1 wk of admission and 45 days of amputation. The treatment team was blinded as to the test results. A direct correlation was observed between wound healing outcome and tcpO2 results (Fisher's exact test [FET], P = 0.03), and no patient with a tcpO2 of < or 15 mm Hg healed during their rehabilitation stay (FET, P = 0.006). TcpO2 of < or = 15 mm Hg was significantly correlated with prolonged length of stay (Point Biserial Correlation Coefficient [rpbi], = -0.835; P = 0.01), delayed prosthetic fitting (rpbi = 0.742; p = 0.01), and poorer wound healing at admission (rpbi = 0.932; P = 0.001). Postoperative tcpO2 measurement may have use in objectively identifying patients at greater risk of delayed wound healing and prosthetic fitting, although further study is warranted. PMID- 7779330 TI - Transcutaneous electrical nerve stimulation. Relevance of stimulation parameters to neurophysiological and hypoalgesic effects. AB - Although Transcutaneous Electrical Nerve Stimulation (TENS) has become a popular modality in pain management over the past 20 yr, there is still debate over its mechanisms of action and the precise relevance of stimulation parameters to its hypoalgesic effects. Thus, confusion still surrounds the selection of optimal stimulation parameters. Two separate studies (total n = 88) were carried out to investigate the effect of four combinations of TENS pulse durations (50 microseconds & 200 microseconds) and frequencies (4 Hz and 110 Hz) on nerve conduction in the human superficial radial nerve and on Mechanical Pain Threshold (MPT) within the associated sensory distribution of the nerve over the dorsum of the hand. Results showed that application of one combination of TENS parameters (110 Hz, 200 microseconds) directly over the course of the nerve produced a significant increase in both peripheral nerve conduction latency (P < or = 0.05; analysis of variance (ANOVA)) and MPT (P < or = 0.01). In addition, there was a high correlation (r = 0.9) between shifts in MPT and negative peak latency for the groups treated with this combination of TENS parameters. The results of this study thus illustrate that combinations of TENS parameters are important to the peripheral neurophysiological effects of this modality and, further, its associated hypoalgesic effects, at least on the model of pain used here. PMID- 7779331 TI - Facilitatory effect of thinking about movement on motor-evoked potentials to transcranial magnetic stimulation of the brain. AB - Two experiments using transcranial magnetic stimulation (TMS) were undertaken to investigate facilitatory effects of thinking about a specific movement without voluntary discharges on motor-evoked potentials (MEP). First, surface electromyographic (EMG) responses from the abductor pollicis brevis were recorded with maximal stimulator output in the three conditions: the muscle being at rest, contracting with 10% of maximal muscle activity, and with the subject "only thinking" about thumb abduction (nine subjects). Median value of MEP amplitudes during "only thinking" was twice that at rest (P = 0.008) and one-half that during voluntary contraction (P = 0.008). Second, needle EMG responses from the first dorsal interosseus were compared at rest, during thinking about index finger abduction, and during TMS at threshold intensity. Four normal subjects were tested with stimulation of each cerebral hemisphere for a total of eight tests. The number of detectable MEP responses of 20 stimuli to one hemisphere was counted for each condition of rest or thinking. The mean MEP response rate during thinking (58%) was higher than that at rest (12%) (P < 0.005). These results demonstrate that thinking about a specific movement has facilitatory effects on MEP and that the degree of facilitation in thinking is smaller than in voluntary contraction. PMID- 7779332 TI - Prevalence of depression and outcome on the geriatric rehabilitation unit. AB - Although numerous studies have examined the prevalence of depression after stroke and its relationship to functional outcome, minimal research attention has been focused on depression in the acute inpatient rehabilitation setting. Fifty-one consecutive admissions to a geriatric rehabilitation unit were screened for depression using the Geriatric Depression Scale at both admission and discharge. Depressed v nondepressed patients were compared on the following variables: age, length of stay (days), admission Functional Independence Measure (FIM) score, discharge FIM score, change in FIM score, Mini-Mental State Exam score, and discharge to nursing home v home. Depression was prevalent in 29.4% at admission. Depression at admission was not associated with any significant differences in the above variables, but patients classified as depressed at discharge had lower FIM scores at both admission and discharge. Clinical implications and recommendations for future research are discussed. PMID- 7779333 TI - Admission motor impairment as a predictor of physical disability after stroke rehabilitation. AB - The purpose of this study is to investigate the Fugl-Meyer Motor Impairment Scale and physical disability as measured by the Functional Independence Measure (FIM) as predictors of physical independence after stroke inpatient rehabilitation. Forty-eight patients admitted to a rehabilitation hospital within 6 wk of their first unifocal stroke were prospectively studied. Upper and lower extremity Fugl Meyer scores were obtained near rehabilitation admission. FIMs were obtained on admission and discharge. Discharge FIM self-care was predicted best by admission FIM total (rs = 0.75; P < 0.0001), although admission FIM self-care, other FIM components, and upper- and lower-extremity Fugl-Meyer scores were also good predictors. Discharge FIM mobility and locomotion correlated well with their admission counterparts (rs = 0.54 and 0.45; P < 0.001 and < 0.01, respectively) but were even more strongly related to admission Fugl-Meyer scores (rs = 0.63 and 0.74, respectively; P < 0.0001). As expected, cognitive and psychosocial components of the FIM at discharge correlated poorly with admission Fugl-Meyer. These data confirm the strong motor impairment basis for the physical disability subdimensions of the FIM and suggest that dependency in physical activities of daily living after stroke is primarily determined by degree of motor impairment. PMID- 7779334 TI - Journal clubs. Prevalence, format, and efficacy in PM&R. AB - Journal clubs can play an integral part in graduate medical education. They promote critical thinking, dissemination of information, and research and impact clinical practice. Little has been written, however, about how to organize a journal club or improve its efficacy. Although numerous articles discuss how journal clubs can be used to evaluate medical literature, only a few have examined what physicians are actually doing. We surveyed all accredited PM&R program chief/residents to ascertain the prevalence, format, and efficacy of PM&R residency journal clubs. All programs that responded (89%) reported having a journal club, with most stating its purpose was to disseminate information from the current literature. Review of classic articles and specialty topics (e.g., electromyography, sports medicine) was fairly uncommon. Eighty-four percent of journal clubs were department-sponsored, and most met monthly for 1 hr during the workday. Typically, four or more articles were presented under the guidance of the chief or other resident. Impacting clinical practice and teaching critical analysis were other important goals of the journal clubs, yet most (76%) lacked an organized method for critical review. This, in addition to poor faculty attendance, was a chief concern of those surveyed. Surprisingly, journal club participation was not felt to significantly alter the amount of reading residents did. Although most felt their journal clubs were successful, improving faculty participation, strengthening critical analysis skills, identifying and incorporating classic articles, improving clinical relevance, and providing a mechanism for feedback may further improve journal club efficacy and participant satisfaction. PMID- 7779336 TI - Need for academic physiatry in the era of health care reform. PMID- 7779335 TI - Guillain-Barre syndrome leading to a conversion reaction in a teenage girl. Case report. AB - Conversion disorder can sometimes simulate Guillain-Barre Syndrome (GBS). This often involves the mimicry of organic symptoms similar to those experienced by a relative or acquaintance. The patient with the conversion unconsciously adopts these symptoms to convert their psychologic stress to a physical phenomenon. This case is of 15-yr-old girl who had a documented case of GBS and who subsequently had recurrent episodes of a conversion disorder that simulated her original GBS presentation. The methods for diagnostically separating recurrent GBS from conversion reaction are noted. PMID- 7779338 TI - Failure to diagnose osteoporosis. PMID- 7779337 TI - Epidemiology of walker-related injuries and deaths in the United States. PMID- 7779339 TI - Conference report: an agenda for medical rehabilitation outcomes research. AB - On August 29 to 31, 1994, a conference was conducted to develop recommendations for needed initiatives in medical rehabilitation outcomes research. Organized by the National Center for Medical Rehabilitation Research and cosponsored with the Agency for Health Care Policy and Research, the conference was entitled "An Agenda for Medical Rehabilitation Outcome Research." The resulting recommendations are presented in four areas: philosophic issues; strategy and design issues; measurement of disability and handicap; and measurement of quality of-life and of health status. PMID- 7779340 TI - Four well documented cases of adventitious bursae on the distal anterior stumps of below-knee amputees. PMID- 7779341 TI - How many muscles should be studied (via needle electromyography (EMG)) to identify a lumbosacral radiculopathy. PMID- 7779342 TI - Parent perspectives of peer relationships and friendships in integrated and specialized programs. AB - In-depth interviews of a large community-based sample of mothers of preschool-age children with established disabilities and those classified as at-risk were conducted focusing on issues of children's peer relations and friendships. Results revealed that mothers of children enrolled in both integrated and specialized programs perceived their respective settings as valuable for the development of their child's peer relations and friendships. Mothers of children in integrated settings reported that their child played better and was more social due to the participation of children without special needs. A similar pattern was obtained for mothers of children enrolled in specialized programs in response to a hypothetical situation. Nevertheless, both groups of mothers were clearly concerned about peer rejection and noted the importance of having other children with special needs in the program available as a means of promoting tolerance and acceptance. PMID- 7779343 TI - Emotion specificity in mental retardation. AB - The emotion-specificity hypothesis states that mental retardation is associated with deficits in decoding facially expressed emotions that cannot be fully accounted for by MA. Research has demonstrated repeatedly that subjects with mental retardation do not perform as well on emotion recognition tasks as do control subjects but not whether those performance deficits are specific to affective cues. The emotion-specificity hypothesis was tested further with three groups of 16 subjects: adults with mild to moderate mental retardation, similar age adults without mental retardation, and children without mental retardation matched for mental age (MA). Subjects completed the Facial Discrimination Task, which has two subtasks consisting of 40 monochrome facial photographs, and rated stimuli on scales ranging from happy to sad or from young to old. Results supported the emotion-specificity hypothesis: The retarded group was significantly less accurate on the emotion task than were both control groups. On the age task the retarded adult group and nonretarded child group were less accurate than the adult control group. PMID- 7779344 TI - Elderly mothers caring at home for offspring with mental retardation: a model of permanency planning. AB - A theoretical model of permanency planning based on the double ABCX model of family stress and adaptation (McCubbin & Patterson, 1982) was tested using structural equation modeling. We interviewed 235 mothers, ages 58 to 96, who cared for adult offspring with mental retardation at home. Four variables were confirmed to directly influence their stage of planning: use of services for offspring, non-use of avoidance coping, the self-perception of being adversely affected by age-related changes, and help from offspring without mental retardation. Variables found to affect planning indirectly were perceived need for services, mothers' subjective burden, extent of caregiving tasks, offsprings' disability, and mothers' disability. PMID- 7779346 TI - Effect of object and movement cues on receptive communication by preschool children with mental retardation. AB - Preschool children with mental retardation typically have delays in language comprehension that may result in difficulty understanding spoken messages. The effect of the systematic application of object and movement cues was investigated to determine whether either or both cues would facilitate children's comprehension of a partner's intended referent during play and snack activities. Children were presented with stimulus items that the communication partner referred to under three conditions: object cue and speech, movement cue and speech, or speech alone. All children identified the intended referents with fewer trials to criterion when object or movement cues were used with speech than when speech alone was employed. PMID- 7779345 TI - Psychotropic drugs in group homes: prevalence and relation to demographic/psychiatric variables. AB - All 1,101 clients residing in over 120 group homes of a residential services agency were surveyed on one date for presence of psychotropic medication. In all, 27% received one or more psychotropic drugs for behavioral or emotional disorders. Disorders and target behaviors listed for each drug group were examined and the relations between drug groups and diagnostic/demographic variables analyzed. In addition, logistic regression analyses were used to examine subject variable/drug relations further and the likelihood of receiving a specific class of medication given the presence of a subject variable. Certain physical and sensory handicaps were associated with less medication use. Generally speaking, the existence of DSM diagnoses (especially psychosis and mood disorder) and certain target behaviors were associated with greater medication use. In the main, medication use was consistent with known or presumptive indications for the respective drug groups, although unestablished applications were also observed. PMID- 7779347 TI - Measuring behavioral phenotypes: provocations from the "new genetics". AB - Recent revolutionary advances in genetics bring a renewed importance to the behavioral phenotypes of mental retardation syndromes. Although the so-called "new genetics" calls for improved research on syndromic behavior, this work has not been a priority in the larger mental retardation field. Further, the work has suffered from inconsistent definitions and methodologies. In this paper key properties of behavioral phenotypes were clarified, including within-syndrome variability and between-syndrome similarities and qualitative differences. Three strategies were offered that improve the traditional focus on easily observed syndromic traits: a psychiatric approach, psychometric methods, and syndrome specific observations. The need to combine these approaches was discussed as were complications of the work due to developmental and environmental issues. PMID- 7779348 TI - Benefit-cost analysis of community residential versus institutional services for adults with severe mental retardation and challenging behaviors. AB - A benefit-cost analysis was conducted to compare services in community residences versus an institution for 11 individuals with severe mental retardation and challenging behaviors who had been moved from an institution to a community setting. Effects that were not readily quantifiable in economic terms also were examined. Overall, the community-based program costs represented slight public savings over costs of the state institution. However, community living netted significant increases in variables such as resident's social networks, opportunities for integrated activities, and income. PMID- 7779350 TI - Relations of scores on the Stanford Binet Fourth Edition and form L-M: concurrent validation study with children who have mental retardation. PMID- 7779349 TI - Early intervention for low birthweight, premature infants: participation and intellectual development. AB - The Infant Health and Development Program was an eight-site randomized controlled trial of comprehensive early intervention for low birthweight, premature infants during the first 3 years of life in which intellectual development was an outcome of major importance. At 24 and 36 months, but not at 12 months, higher Mental Development Index and IQ were associated with higher levels of participation in the intervention. In a longitudinal analysis of these data, we found that the intellectual development of children in the intervention group was associated with each of the three intervention modalities (the number of home visits received, days attended at child centers, and the number of parent meetings attended) but not with children's background characteristics (i.e., maternal education, birthweight). We suggest that these findings represent a dose-response relation between intervention and outcome. PMID- 7779351 TI - Conditional discrimination by adults with mental retardation: establishing relations between physically identical stimuli. PMID- 7779352 TI - 2nd European Conference on Vaccinology: Combined Vaccines for Europe; Pharmaceutical, Regulatory and Policy-Making Aspects. Proceedings. Brussels, Belgium, 18-20 May 1994. PMID- 7779353 TI - Regulatory framework of immunologicals in the European Union. PMID- 7779354 TI - Immunisation policies and programmes in Europe. PMID- 7779355 TI - Development of combined vaccines: manufacturers' viewpoint. AB - Rapid and exciting research breakthroughs in the fields of immunology and molecular biology in recent years have greatly enhanced the potential for developing new vaccines or improving existing ones. The resulting rising number of diseases that can be prevented by vaccination, coupled with the growing trend of preferring cost-effective preventive medical interventions over expensive therapeutic modalities, has increased the complexity of administering to all those who need them, the many different vaccines that will soon be available. Hence attention in the field of vaccinology is now focusing on the development of combined vaccines that, in a few inoculations, can elicit protection against as many diseases as possible. Some of the recent achievements, future objectives and difficulties of vaccine manufacturers in the development of combined vaccines are surveyed. PMID- 7779356 TI - Epidemiological views into possible components of paediatric combined vaccines in 2015. AB - Efforts to develop combined vaccines for childhood immunization schedules will during the next years focus on combined administration of the existing vaccines which have already shown their impact. First candidate components for more wide spectrum combinations could be the new antigens against severe invasive infections caused by encapsulated bacteria. Multivalent pneumococcal and meningococcal group A and C conjugate vaccines are already in clinical trials, and the same is true of the first candidates for the meningococcal group B vaccine. Pneumococcal conjugate vaccines are also important in prevention of a large variety of respiratory infections. Since viruses are important causative agents of bronchiolitis and pneumonia, components of the paediatric combined vaccine should include at least respiratory syncytial virus, and possibly also other respiratory viruses like parainfluenza and adenoviruses. The third group of diseases to be considered from the preventive point of view are congenital infections, and vaccines against herpes simplex viruses, cytomegalovirus, or group B streptococci might be included in a combined vaccine to be administered to adolescents in order to afford protection to their future children. PMID- 7779357 TI - Combination vaccines: present practices and future possibilities. PMID- 7779358 TI - Role of the European Commission in pharmaceuticals research. PMID- 7779359 TI - Pharmaceutical aspects of combined vaccines: a manufacturer's perspective. PMID- 7779360 TI - Combination of DTP and Haemophilus influenzae type b conjugate vaccines can affect laboratory evaluation of potency and immunogenicity. AB - A commonly used Diphtheria-Tetanus-Pertussis (whole-cell) vaccine was combined with each of three different Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines. Each Hib vaccine incorporated one of three different protein conjugates: tetanus toxoid, diphtheria CRM197 toxoid or group B Neisseria meningitidis outer membrane vesicles. The effects of these combinations on the subsequent laboratory control testing were examined. The addition of the Hib vaccines had no significant effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid had dramatic effects on tetanus potency and immunogenicity when assayed in mice. This combination resulted in a five-fold potentiation of the tetanus potency and a similarly large increase in the antibody responses to tetanus toxin and toxoid. The level of the antibody response to the Hib polysaccharide in this vaccine was also elevated, more than 20-fold, as a result of the combination. Such phenomena were not evident with combinations involving the other two Hib vaccines. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide tetanus protein conjugate vaccine. PMID- 7779361 TI - Combined vaccines--the European contribution. AB - Efforts to develop new vaccine combining as many immunogens as possible have stimulated researchers of most European vaccine manufacturers to contribute with new vaccine designs. Besides the conventional combinations the following approaches are under development: new carrier systems for inactivated antigens; new adjuvants for subunit antigens; live attenuated combined vaccines; vector combined vaccines; synthetic polypeptide combined vaccines. The availability of new combined vaccines will greatly facilitate immunization programmes for the control of many diseases around the world. The whole of modern society in general is moving towards prevention--for example on safety issues--as well as in medicine, where prophylactic approaches are medically, scientifically, ethically, and mortally more justifiable as well as being more cost-effective. Besides improving the health and overall quality of life of the world's population, the use of combined vaccines will further reduce already overstretched health care budgets. PMID- 7779363 TI - Stability testing on vaccines--results of activities of the International Conference on Harmonization (ICH) of technical requirements for registration of pharmaceuticals for human use. PMID- 7779362 TI - Control testing of combined vaccines: a consideration of potential problems and approaches. AB - Vaccines comprising combinations of diphtheria, tetanus and pertussis (DTP) components with Haemophilus influenzae b polysaccharide--protein conjugates (DTP Hib) are now available. Combinations of DTP-Hib with additional components such as inactivated poliomyelitis vaccine, hepatitis B vaccine, meningococcal and pneumococcal polysaccharide-protein conjugates are under development. Other combinations, such as Hib vaccine with meningococcal A, B and C components and possibly pneumococcal conjugates, or non-capsulated Haemophilus components combined with pneumococcal conjugates, developed against bacterial meningitis and otitis media respectively, are of potential interest. Combination vaccines against enteric infections and including potentially cholera, typhoid, ETEC, Shigella, rotavirus and possibly Campylobacter and Helicobacter components, may become available in the longer term. The control of these combinations is likely to be based on pharmacopoeial requirements for the individual components. However, the evaluation of combinations may not be straightforward and the interaction of the components with each other may influence reactogenicity, immunogenicity and stability and will complicate laboratory control tests. Indications of this have already arisen with some DTP-Hib combinations but are likely to increase as additional components are added. For example, the use of diphtheria and tetanus proteins as carriers for multiple polysaccharide conjugates may lead to excessive antitoxin production and epitope suppression of anti-polysaccharide responses. Other problems may result from competition for binding sites on adjuvant molecules. The requirements for new vaccine combinations need to be considered carefully and should not be made solely on assumptions based on the properties of individual components. PMID- 7779364 TI - The system of mutual recognition of batch release in the EU--implications for combined vaccines. PMID- 7779365 TI - Combined vaccines: policy and practice in the European Pharmacopoeia. PMID- 7779366 TI - Definition of minimum standards for immunogenicity--potential problems of serological correlates--possible interference. Serological correlates for diphtheria-tetanus-whole cell pertussis vaccines. PMID- 7779368 TI - Difficulties in establishing a serological correlate of protection after immunization with Haemophilus influenzae conjugate vaccines. AB - In several studies the protective concentration of anti-Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) antibodies has been concluded to be around 0.04 to 0.20 microgram/ml. After the Finnish Hib polysaccharide vaccine trial it was estimated that 1 microgram/ml has to be achieved to predict long term protection after vaccination. These estimates of protective anti-Hib PS antibody concentrations were based on the assumption that protection from invasive Hib disease is mediated by antibodies and the role of cell-mediated immunity is negligible. This assumption was justified since the Hib PS is a T cell-independent antigen. The matter becomes quite different when the character of the PS vaccine is altered by conjugating it to a protein carrier, so that it acquires the ability to stimulate T cells, and the immunological memory plays a role in the protection. The immunized infants are thought to be able to respond with a rapid and high antibody response after exposure to the organism. After immunization with conjugate vaccines, protection can be seen at a lower serum antibody concentration than after polysaccharide vaccine. In addition, higher avidity of anti-Hib PS antibodies is associated with the response to conjugate than PS vaccine, and there are differences between the conjugates. This might have an influence on the functional activity of the antibodies. Hib conjugate vaccines are also able to reduce the carriage rate of Hib. This should be kept in mind when estimating what is needed from protective immune response after immunization with Hib conjugate vaccines. PMID- 7779369 TI - Clinical evaluation of HB vaccine as a component of combination vaccines. PMID- 7779367 TI - Immunogenicity of acellular pertussis vaccines. PMID- 7779370 TI - Definition of acceptable levels for safety and potential problems. PMID- 7779371 TI - Problems in the choice of combined vaccines for Europe. PMID- 7779373 TI - American experience in harmonizing national policy. PMID- 7779374 TI - Pertussis in combined vaccines. PMID- 7779372 TI - Cost benefit of combining antigens. PMID- 7779375 TI - Are different combined vaccines needed in different parts of Europe? A point of view from a northern-European country. PMID- 7779377 TI - Inclusion of IPV in combined vaccines. PMID- 7779376 TI - Integration of hepatitis B and Hib vaccine in national vaccination programmes in southern Europe. PMID- 7779378 TI - Booster doses and combined vaccines. PMID- 7779379 TI - Uracil-USE, an improved method for site-directed mutagenesis on double-stranded plasmid DNA. PMID- 7779380 TI - Gene assembly-aided mutagenesis (GAAM). PMID- 7779381 TI - Improved recombinant PCR mutagenesis procedure that uses alkaline-denatured plasmid template. PMID- 7779382 TI - Visual detection method for identifying recombinant bacterial colonies. PMID- 7779384 TI - DNA sequencing with delta Taq DNA polymerase. PMID- 7779383 TI - Direct cloning of mutant alleles from the bacterial chromosome into plasmid vectors in vivo. PMID- 7779385 TI - Efficient creation of sequencing libraries from blunt-ended restriction enzyme fragments. PMID- 7779386 TI - Nonradioactive method for restriction mapping of lambda phage DNA. PMID- 7779388 TI - DIG-labeled RNA in situ hybridization without coverslipping. PMID- 7779387 TI - Method identifying hybridizing regions of DNA within an insert. PMID- 7779389 TI - Efficient isolation of whole genomic DNA from cell cultures and blood samples. PMID- 7779390 TI - Extraction of genomic DNA from extracellular polysaccharide-synthesizing gram negative bacteria. PMID- 7779391 TI - 33P and beta-Imager: application for genotyping of microsatellite markers. PMID- 7779392 TI - Heat-treated bovine serum albumin is a better blocking reagent for adhesion studies. PMID- 7779393 TI - Detection of wild-type contamination in a recombinant adenoviral preparation by PCR. AB - A rapid and sensitive method of detecting wild-type virus contamination is needed for the preparation of recombinant adenoviruses for adenoviral vector applications in which purified vectors free of wild-type virus are required for preclinical studies and clinical trials. In response to this demand, we developed a PCR assay that uses two pairs of primers in the same reaction to detect adenoviral E1 DNA with co-amplification of E2B DNA as an internal control. Template DNA preparation was simplified and required only 365 microL of culture medium of 293 cells that displayed a cytopathic effect following adenovirus infection. Evaluation of the sensitivity of the assay demonstrated that it detected the E1 DNA in a reconstruction of one plaque-forming unit (pfu) of wild type virus in 10(9) pfu of recombinant viruses. This method may be useful for quality control in the production of adenoviral vectors free of wild-type virus for gene therapy applications. PMID- 7779394 TI - Direct sequencing of DNA isolated from mRNA differential display. AB - A recently developed mRNA differential display technique has a potential power for identifying genes that are differentially expressed in a variety of in vitro and in vivo systems. One critical feature of this technique is to display most of the mRNA population on a sequencing gel after polymerase chain reaction using a 5' decamer and a 3' T12MN anchored primer. However, these primers are too small to be successfully used as a sequencing primer using the classical sequencing protocol. In the present report we described the application of an extended primer set for the re-amplification after mRNA differential display, which renders the amplified DNA suitable for direct sequencing using either of these extended oligonucleotides as a primer without further subcloning. This improved technique will greatly save the time, cost and labor-intensive work for the discovery of genes using mRNA differential display. PMID- 7779395 TI - Improved strategy for large-scale DNA sequencing using DNaseI cleavage for generating random subclones. AB - Large-scale DNA sequencing projects require the use of specific and reliable strategies. Here, we describe an improved strategy using DNaseI cleavage and sequencing strategy using DNaseI cleavage and sequencing from both ends of the plasmid inserts. This strategy yields better results than those obtained using partial digestion with restriction enzymes and cloning in single-stranded vectors. PMID- 7779397 TI - Determination of the poly(A) tail lengths of a single mRNA species in total hepatic RNA. AB - Poly(A) tail length is important in the stability and translation of mRNA. We describe procedures for the rapid and reproducible analysis of poly(A) tail length of a single mRNA species contained in a sample of total hepatic RNA. A short 3' fragment of a specific mRNA is prepared by RNase H digestion of the targeted mRNA region annealed to a short DNA oligonucleotide. The length of the poly(A) tail of the 3' fragment is then determined by running the sample on a polyacrylamide gel, by electrophoretic transfer, by probing with a radiolabeled cDNA and by comparing the size of the detected region with a specific RNA ladder or a DNA ladder. PMID- 7779396 TI - Multisite oligonucleotide-mediated mutagenesis: application to the conversion of a mitochondrial gene to universal genetic code. AB - Using multisite oligonucleotide-mediated mutagenesis in conjunction with a mutagenesis selection procedure and rapid screening by allele-specific oligonucleotide hybridization has allowed us to develop a reliable protocol that enables a large number of base changes to be introduced rapidly into a piece of DNA, with the minimum number of manipulations. We have applied this protocol to generate synthetic versions of four mouse mitochondrial genes capable of being expressed in the nucleus/cytosol. PMID- 7779399 TI - Identification of ABO alleles on forensic-type specimens using rapid-ABO genotyping. AB - Historically, forensic and clinical laboratories utilize serological techniques to identify ABO blood types. These techniques rely on the detection of ABO associated proteins and are sensitive with very accurate results. This laboratory has simplified the identification of ABO types by taking advantage of previously reported ABO DNA sequence differences. The Rapid-ABO technique involves a two step process: (i) amplification of DNA samples using primer sets specific for the ABO alleles and (ii) electrophoresis and visualization of amplified ABO fragments on a 3% MetaPhor agarose gel. The major advantage of the Rapid-ABO technique is the identification of ABO genotypes compared to serological tests for ABO phenotypes. This two-step process identifies six possible ABO genotypes including AB, AA, BB, AO, BO and OO. The Rapid-ABO protocol works well with DNA extracted organically or using Chelex 100. Results can be obtained in less than a day utilizing 2 ng of DNA in the amplification reaction. Analysis of 23 animal species shows the Rapid-ABO primers amplify ABO alleles from only human, chimpanzee and gorilla DNA. PMID- 7779398 TI - Restriction endonuclease fingerprinting (REF): a sensitive method for screening mutations in long, contiguous segments of DNA. AB - Restriction endonuclease fingerprinting (REF) is a modification of single-strand confirmation polymorphism (SSCP) that was developed to detect the presence of essentially all mutations in a 1-kb segment. To test REF, a 1-kb segment of the human factor IX gene was amplified with PCR and digested with each of five groups of restriction endonucleases. The endonucleases in each group were chosen so that the average size of the fragments was about 150 bp. After separate digestions, the products were mixed, 5' end-labeled with T4 polynucleotide kinase, denatured and electrophoresed under nondenaturing conditions. Each lane screened 1 kb and typically contained 68 segments (6.8 fragments per average digestion x 5 digestions x 2 strands). REF was performed with 5.6% polyacrylamide and 7.5% GeneAmp at temperatures of either 23 degrees or 8 degrees C. Point mutations resulted in the gain or loss of a restriction site in 21% of 24 test mutations (informative restriction component). In cases in which the restriction component was not informative, mutations were detected if any of the five mutation containing restriction fragments (producing 10 single-stranded segments) displayed abnormal mobility (SSCP component). The average efficiency per single stranded segment of the SSCP component for the 24 point mutations ranged from 49% for polyacrylamide at 23 degrees C to 68% with GeneAmp at 8 degrees C. REF detected 96% of the mutations with polyacrylamide at 23 degrees C and 100% with GeneAmp at 23 degrees or 8 degrees C. GeneAmp at 23 degrees and 8 degrees C also detected 100% of a subsequent blinded sample that contained normal controls and 27 different point mutations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779400 TI - Generation of high-titer retroviral vectors following receptor-mediated, adenovirus-augmented transfection. AB - A new procedure is described for the generation of high-titer, helper-free retrovirus vectors employing receptor-mediated, adenovirus-augmented transfection into a standard packaging cell line. Viral titers are increased 30-fold to 100 fold in transiently (> 10(5) infectious units per mL) and stable (> 10(7) infectious units per mL) transfected cells as compared with either CaPO4-mediated transfection or retroviral infection of a packaging cell line. Further, expression of the transduced genes was drastically increased in the transfected cells, but, as expected, there was no difference in transduction efficiency and gene expression in the infected target cells. The increases in viral titers were most likely due to the high number of stable, integrated copies of the vector plasmid DNA in the resulting packaging lines following G418 selection. In addition, experiments generating recombinant retroviruses from non-packaging cell lines are presented. The results suggest that this procedure may be of use to generate high-titer retrovirus vectors in packaging cell lines as well as in primary cells, thus providing a technical basis for in vivo gene transfer upon transplantation of these cells into various organs. PMID- 7779401 TI - A pre-loading method of evaluating gap junctional communication by fluorescent dye transfer. AB - We describe a simple method for evaluating gap junctional communication (GJC) between cells in culture. The procedure involves pre-loading cells with two fluorescent dyes: calcein and DiI. Calcein is able to pass through gap junctions, while DiI is not. These pre-loaded cells are then plated with unlabeled cells. The number of cells receiving calcein from each pre-loaded cell can then be quantified after the cells settle on the plate. Potent and reversible inhibitors of GJC can be used in this system to evaluate dye transfer within a given period of time. PMID- 7779402 TI - Fast hybridization solution for the detection of immobilized nucleic acids. AB - We have developed a fast hybridization solution, termed ExpressHyb, for the rapid and sensitive detection of nucleic acids immobilized on membrane supports. This solution reduces typical hybridization times of 12-24 h to as little as 1 h while simultaneously increasing the sensitivity of detection in many applications. Using ExpressHyb, human beta-actin mRNA was detected on a human multiple tissue Northern (MTN) blot following a 30-min hybridization, with optimal detection occurring with a 1-h hybridization interval. The moderately abundant human glyceraldehyde-3-phosphate dehydrogenase (G3PDH) mRNA was detected using similar hybridization conditions and yielded improved signal-to-background characteristics relative to overnight hybridizations in conventional solutions. ExpressHyb can be used with either 32P- or digoxigenin-labeled probes and works effectively with both cDNA and oligonucleotide probes. For non-isotopic detection in particular, ExpressHyb reduces the nonspecific background commonly encountered with this technique. In cDNA library screening, ExpressHyb was found to both reduce the time required for effective hybridizations and to increase the number of positive colonies obtained relative to conventional overnight procedures. Taken together, these results illustrate the broad capability of ExpressHyb Hybridization Solution to improve nucleic acid detection in a variety of important techniques. PMID- 7779403 TI - Quantitation of cellular receptors by a new immunocytochemical flow cytometry technique. AB - Flow cytometry provides a rapid qualitative method for analyzing the binding of a fluorescent probe to a cell. To quantitate the binding of a probe using flow cytometry, one must be able to first calibrate the fluorescent signal with some known standard. We have compared a new one-step method with a previous two-step method for determining the number of binding sites (receptors) on the surface of cells using immunofluorescent staining of the cells and analysis by flow cytometry. Experimentally, recombinant chinese hamster ovary cells, expressing cell surface glycoprotein receptors, IIb/IIIa or Mac-1, were assayed using specific mouse monoclonal antibodies against these receptors. The two methods yielded comparable results and, depending on the cell type, detected anywhere from 100,000 to 300,000 antibody-binding sites per cell, respectively. PMID- 7779404 TI - Structure-function relationships for the EGF/TGF-alpha family of mitogens. AB - Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) are ligands for the EGF-receptor and act as mitogens for a variety of tissues. TGF-alpha, in particular, has been implicated as an autocrine growth factor for several cancer cell lines. Over the last 10 years many groups have examined the structure-function relationships in EGF/TGF-alpha in attempts to develop antagonists or agonists. In this review the results of these studies are summarised and related to the three-dimensional structure of EGF/TGF-alpha. The difficulties associated with the purification and characterisation of analogues of EGF/TGF-alpha and with the biological assays are discussed. It is clear that these difficulties have, in some cases, led to apparently contradicting results. The available binding data indicate that the receptor interaction surface for EGF/TGF-alpha might encompass one complete side of the molecule with a few strong binding determinants, in particular Arg41 and Leu47. The arginine at position 41 is the most critical residue and its full hydrogen-bonding capacity is needed for strong binding of EGF/TGF-alpha to the EGF-receptor. As this side of the molecule consists of residues from both the N- and C-terminal domain, it seems unlikely that agonists or antagonists can be developed on the basis of short peptides taken from the primary sequence. This concept is supported by the available binding and activity data. PMID- 7779405 TI - Triplex-forming oligonucleotide binding represses transcription of the human c erbB gene in glioma. AB - Mixed purine-pyrimidine oligodeoxynucleotides were designed to form collinear DNA triplexes with pyrimidine-rich elements in the EGFR gene promoter. Their effects as mediators of human epidermal growth factor receptor (EGFR) gene transcription and subsequent gene expression were evaluated using human squamous cell carcinoma (A431) and human glioma cell line (U251MG and U87MG). Gel shift analysis indicated that the oligonucleotide forms a collinear triplex within the duplex Sp 1 binding site. An in vitro assay system revealed a correlation between triplex formation and the repression of EGFR transcription. We postulate that guanine residues are not always optimum in apposition to G-C pairs to form triple helices in the target. Site-specific oligodeoxynucleotides binding to a DNA duplex may serve as the basis for an alternative program of gene control in vitro. PMID- 7779407 TI - Immunolocalisation of vascular endothelial growth factor in human endometrium. AB - Angiogenesis is an essential component of endometrial regeneration after menses in preparation for implantation. Vascular endothelial growth factor (VEGF) is a secreted angiogenic peptide with mitogenic activity specific for endothelial and trophoblast cells. VEGF-immunoreactivity was detected in glandular epithelium throughout the menstrual cycle by immunohistochemistry, but, showed cyclic variation in the stroma and the blood vessels. During the early proliferative phase, strong staining was seen in the glandular epithelial cells while staining in the stroma was confined to a subpopulation of stromal cells and endometrial blood vessels appeared negative. In contrast, very intense staining of the endometrial stromal cells was seen in the mid proliferative endometrium possibly due to increased synthesis of VEGF by oestrogen. In the late proliferative endometrium, staining was seen in the endothelial cells and the perivascular stromal cells around the endometrial blood vessels. The greatest degree of immunostaining of stromal cells was observed in the mid to late proliferative endometrium. Throughout the secretory phase no staining was seen around the endometrial blood vessels and staining of endometrial stromal cells was confined to early secretory endometrium. In the late secretory endometrium only the glands were positive to VEGF antibody. The observed increase in the immunostaining of stroma suggests increased production of VEGF from early to mid and late proliferative endometrium which parallels the increase in the oestradiol levels in the proliferative phase of the menstrual cycle. It is proposed that VEGF may serve as a paracrine mediator of the effects of ovarian steroids on endometrial vascular development. PMID- 7779406 TI - NMR studies of a murine-human chimera of leukaemia inhibitory factor (LIF). Comparison with human LIF. AB - Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine active on many cell types. We present here 1H NMR studies on the solution properties and stability of MH35, a chimera of murine and human LIF which can be expressed at high levels in Escherichia coli, thus enabling efficient labelling of the protein with the stable isotopes 13C and 15N. MH35 has 85% sequence identity with human LIF and similar activity in biological assays. The 1H chemical shifts of the 12 conserved aromatic residues and the pKa values of the five conserved histidine residues in MH35 and human LIF are very similar. Temperature dependence studies indicate that both proteins are stable, with significant conformational changes occurring only above 70 degrees C. These results show that these proteins have a similar overall structure and stability and that MH35 is therefore a suitable analogue of human LIF for structural studies in solution. PMID- 7779408 TI - Effects of transforming growth factor beta 1 on the adenylyl cyclase-cAMP pathway in prostate cancer. AB - We reported previously that MATLyLu rat prostate cancer cells engineered to overproduce transforming growth factor beta 1 (TGF beta 1) produce larger, more metastatic tumors in vivo. We recognized that this ability of TGF beta 1 to act as a positive modulator of prostate tumor behavior might be due to effects of TGF beta 1 on the host and/or on the tumor cells. In this study we demonstrated that the cells themselves respond to endogenously produced TGF beta 1, and that the adenylyl cyclase (AC)-cAMP pathway is affected. TGF beta 1-overproducing cells had lower membrane AC activity, lower intracellular cAMP content, and a lower Gs alpha protein level than did control cells. Prostate cancer cells were growth inhibited by 8-bromo-cAMP or forskolin, agents that elevate intracellular cAMP. Thus, TGF beta 1 overproduction affects the phenotype of the tumor cells, deliberate activation of endogenously produced latent TGF beta 1 is not required (indicating that the cells themselves are capable of activating latent TGF beta 1), and TGF beta 1 overproduction lowers the cellular concentration of the growth inhibitor cAMP. Therefore, TGF beta 1 overproduction could affect tumor behavior in vivo in part via a direct effect on the tumor cells. PMID- 7779410 TI - The Tumor Microenvironment--Its Characterization, Modification and Clinical Implications. Proceedings of an international workshop. Granada, Spain, September 23-25, 1994. PMID- 7779409 TI - Des (1-3) IGF-I potently enhances differentiated cell growth in olfactory bulb organ culture. AB - We recently provided evidence that newborn rat olfactory bulb (OB) could be maintained in serum-free organ culture with combinations of insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF), both of which are locally synthesized. Des (1-3), or truncated, IGF-I is a potent analog of IGF-I isolated from rat and human brain. We proposed in this study to examine the effects of des (1-3) IGF-I on cell function, morphology and on neuronal and glial cell differentiation in our cultured OB model, using cell-specific immunostains for neurons (150 kDa neurofilament) and glial cells (glial fibrillary associated protein--GFAP). OB were cultured in Iscove's serum-free medium containing IGF-I or des (1-3) IGF-I both alone or in combination with bFGF. Dose dependent responses of 14C amino acid uptake showed des (1-3) IGF-I to be 3-5 fold more potent than IGF-I with a half maximal response at about 20 ng/ml in comparison to 100 ng/ml of IGF-I. The maximum response to IGF-I +/- bFGF was seen at 150 ng/ml; a ten-fold higher dose of insulin +/- bFGF was required to achieve the same response. While morphology was close to fresh 6 day OB following culture with IGF I (150 ng/ml) and bFGF (25 ng/ml), the substitution of des (1-3) IGF-I at 50 ng/ml markedly improved morphology. Neurons were identified following culture in IGF-I or bFGF alone, but showed greater organisation in the mitral layer following combined IGF-I/bFGF culture. However, in contrast to IGF-I (150 ng/ml), des (1-3) IGF-I (50 ng/ml) supported marked neuronal expression. Furthermore, when des (1-3) IGF-I (50 ng/ml) was substituted for IGF-I, in combination with bFGF, the pattern of enhanced neuronal expression in the mitral layer was very close to that seen in the fresh 6 day bulb, with dendrites projecting to the glomerular layer. In OBs treated with no growth factors, or either IGF-I, des (1 3) IGF-I or bFGF alone, glial expression was widespread and poorly organised, suggesting an injury response. In contrast, following treatment with combinations of bFGF with IGF-I or des (1-3) IGF-I, a more ordered, though enhanced glial response was seen in glomerular and granule cell layers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7779411 TI - Modulation of spatial O2 tension distribution in experimental tumors by increasing arterial O2 supply. AB - Tumor oxygenation has been measured polarographically in s.c. implanted DS sarcomas on the dorsum of the hind foot of male Sprague-Dawley rats. pO2 was determined in all 3 spatial dimensions and 3-dimensional pO2 distributions as well as the mean extent of confluent areas with pO2 < 5 mmHg were calculated. Finally, the effect of elevating arterial pO2 (by carbogen breathing) as well as of increasing tumor blood flow (by angiotensin infusion) on the spatial pO2 distribution was analyzed. Depending on the tumor volume, the spatial pO2 distribution is more or less anisotropic. In smaller tumors, areas with physiological pO2 values are found adjacent to large hypoxic areas whereas larger tumors are almost completely hypoxic/anoxic. With carbogen breathing, the mean tissue pO2 is elevated although hypoxia is not eradicated in larger tumors. In small tumors, angiotensin leads to a vasoconstriction of tumor vessels followed by a worsening of tumor oxygenation whereas in large tumors the increased systemic perfusion pressure resulted in an improvement of oxygenation. Thus, carbogen predominantly affects pO2 diffusion by increasing the arterial pO2 whereas angiotensin influences tumor perfusion and leads to an increased oxygen supply to the tumor tissue. PMID- 7779412 TI - The importance of determining necrotic fraction when studying the effect of tumour volume on tissue oxygenation. AB - The relationship between tumour tissue oxygenation and necrosis at different tumour sizes was investigated in a C3H mammary carcinoma implanted in the feet of female CDF1 mice. Experiments were performed using tumours that ranged in size from 80 to 800 mm3. Necrosis was estimated histologically. Tumour tissue oxygenation (pO2) was estimated with an Eppendorf electrode. Our results showed that as tumour volume increased there was a corresponding increase in necrotic fraction ranging from 1% in small tumours up to 51% in large tumours. The percentage of pO2 values < or = 5 mmHg increased from 2% up to 79%, in small and large tumours respectively. After correcting for necrosis, the apparent, significant increase in the % of pO2 values < or = 5 mmHg was lost. We conclude that correcting for necrotic fraction in this tumour model is necessary when attempting to measure tumour oxygenation using electrodes. PMID- 7779413 TI - Use of the comet assay to detect hypoxic cells in murine tumours and normal tissues exposed to bioreductive drugs. AB - The alkaline comet assay was applied to individual cells from mice exposed to two bioreductive drugs, tirapazamine and RSU 1069, with the goal of comparing DNA damage to tumours and normal tissues. More DNA single-strand breaks (SSBs) and a greater heterogeneity in DNA damage were observed in tumour cells than in spleen and marrow cells of mice exposed to 10-100 mg/kg tirapazamine, consistent with the presence of hypoxic cells and the greater bioreductive capacity of tumours. In mice injected with 25-200 mg/kg RSU 1069, aerobic cells exhibited large numbers of SSBs while toxic DNA interstrand crosslinks were produced only in hypoxic cells. Cells from bone marrow and spleen showed extensive numbers of SSBs, but minimal crosslinking compared to tumours where 10-20% of cells were heavily crosslinked. DNA damage produced by these two bioreductive drugs may be useful in estimating the range of individual cell oxygen contents within tumours and normal tissues. PMID- 7779414 TI - Are direct measures of tumor oxygenation reflective of changes in tumor radiosensitivity following oxygen manipulation? AB - The present study investigates the correlation between tumor oxygen availability and radiosensitivity following oxygen manipulation. Previous work has shown that tumors may contain both diffusion- and perfusion-limited hypoxic cells. Recently, the combination of nicotinamide (NIC) administration plus carbogen breathing has been proposed as a means of targeting both hypoxic cell subpopulations. Intravascular HbO2 saturations were measured for KHT murine sarcomas following either NIC, carbogen breathing, or the combination, and compared with determinations of tumor cell survival under matched conditions. The percentage of vessels > or = 25% HbO2 increased significantly for both the carbogen and NIC carbogen combination, while remaining unchanged from controls following NIC. These findings contrast with the survival data, where all treatments showed identical cell survival. A possible explanation is that different proportions of clonogenic versus nonclonogenic cells may be oxygenated by the alternative treatments. Thus direct determinations of alterations in tumor oxygenation may not reflect corresponding changes in radiosensitivity. PMID- 7779415 TI - Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors. AB - The extent of hypoxic regions in a tumor tissue depends on the arrangement, blood flow rate and blood oxygen content of microvessels, and on the tissue's oxygen consumption rate. Here, the effects of blood flow rate, blood oxygen content and oxygen consumption on hypoxic fraction are simulated theoretically, for a region whose microvascular geometry was derived from observations of a transplanted mammary andenocarcinoma (R3230AC) in a rat dorsal skin flap preparation. In the control state, arterial PO2 is 100 mmHg, consumption rate is 2.4 cm3 O2/100 g/min, and hypoxic fraction (tissue with PO2 < 3 mmHg) is 30%. Hypoxia is abolished by a reduction in consumption rate of at least 30%, relative to control, or an increase in flow rate by a factor of 4 or more, or an increase in arterial PO2 by a factor of 11 or more. These results suggest that reducing oxygen consumption rate may be more effective than elevating blood flow or oxygen content as a method to reduce tumor hypoxia. PMID- 7779416 TI - Contribution of transient blood flow to tumour hypoxia in mice. AB - Tumours grown in mice typically exhibit regions of hypoxia believed to result from two different processes: chronic oxygen deprivation due to consumption/diffusion limitations, and periodic deprivation resulting from transient reductions in tumour blood flow. The relative contribution of each is, however, not generally known. We have addressed this issue in transplanted SCCVII squamous cell carcinomas in C3H mice, using a quantitative extension of the fluorescence 'mismatch' technique coupled with cell sorting from irradiated tumours. At least half of the vessels in these tumours exhibit transient perfusion changes. Additionally, a majority of the 15-20% of cells that are sufficiently hypoxic to be resistant to radiation in the SCCVII tumours appear to result from cyclic, not continuous (diffusion-limited) hypoxia. Since different strategies may be necessary to counteract cyclic hypoxia in tumours, the possibility of transient blood flow changes should not be ignored when planning cancer therapy for humans. PMID- 7779417 TI - Reoxygenation in a C3H mouse mammary carcinoma. The importance of chronic rather than acute hypoxia. AB - The role that chronic and acute hypoxia play in tumour reoxygenation after irradiation was investigated in a C3H mouse mammary carcinoma grown in the feet of female CDF1 mice. Tumours at 200 mm3 in size were locally irradiated with a priming dose of 20 Gy and then at various times after given a range of radiation doses under normal or clamped conditions. Local tumour control was determined 90 days later from which the tumour hypoxic fractions were calculated. Untreated tumours contained 23% hypoxic cells. Immediately after 20 Gy this increased to 52% and by 24 h had fallen to 10%. These reoxygenation experiments were repeated, giving either nicotinamide (1000 mg/kg; i.p. injected 30 min before each irradiation) to remove acute hypoxia, or carbogen breathing (for 5 min before and during irradiation) to decrease chronic hypoxia. With nicotinamide the normal hypoxic fraction was reduced to 7%, but after irradiation it had risen to 46% and by 24 h there was full reoxygenation with a value of 5% being observed. Carbogen breathing also decreased the normal hypoxic fraction to 6%, and immediately after irradiation this was increased to 38%. However, by 24 h it was still elevated at around 23%. These results suggest that chronic rather than acute hypoxia is necessary for reoxygenation in this tumour. PMID- 7779418 TI - Relationship between tumour oxygenation, bioenergetic status and radiobiological hypoxia in an experimental model. AB - Tumour oxygenation and bioenergetic status were measured in the same tumour and these results related to radiobiological hypoxia. A C3H mouse mammary carcinoma grown in the feet of CDF1 mice was used. Bioenergetic status was assessed by 31P MRS using a SISCO 7 Tesla magnet, oxygen measurements were done by a polarographic electrode and the hypoxic fraction was determined from direct analysis of the radiation dose-response data. During all examinations restrained, non-anaesthetized mice were allowed to breathe either 100% oxygen, carbogen, normal air, carbon monoxide (CO) at 75, 220, or 660 ppm or had blood flow occluded by clamping. Results showed a significant correlation between the radiobiological hypoxic fraction and % pO2 < or = 5 mmHg under the different treatment conditions, whereas no correlation was found between beta nucleosidetriphosphate/inorganic phosphate (beta-NTP/Pi) ratio and either the hypoxic fraction or the % of pO2 values < or = 5 mmHg under the different treatment conditions. In conclusion, oxygen electrode measurements were sensitive to changes in tumour hypoxia whereas the bioenergetic status alone seemed to be a less precise measure of hypoxia in this tumour model. Furthermore, the present study demonstrated that tumour cells in vivo can actually maintain the bioenergetic status during a period of severe hypoxia. PMID- 7779419 TI - Energy status parameters, hypoxia fraction and radiocurability across tumor types. AB - Under full nutrient in vitro conditions, the cellular adenylate energy charge of six different rodent and human tumor cell types was identical, i.e., 0.94 +/- 0.01, suggesting the potential utility of this parameter as a cell (and tissue) independent marker of nutrient deprivation and hypoxia, across tumor types. The adenylate energy charge values of tumors, arising from these cells, was reduced and variable ranging from 0.72 to 0.91 for the various tumor types. However, neither the tumor adenylate energy charge, NTP/Pi, nor PCr/Pi ratios correlated with the radiobiologic hypoxic cell fractions across tumor types. The reduced adenylate energy charge in vivo suggests varying degrees of nutrient deprivation in the different tumor types, however, factors other than or in addition to hypoxia likely contribute to tumor energy status. PMID- 7779420 TI - Spin-lattice relaxation time of inorganic phosphate in human tumor xenografts measured in vivo by 31P-magnetic resonance spectroscopy. Influence of oxygen tension. AB - Previous 31P-magnetic resonance spectroscopy (31P-MRS) studies have suggested that the spin-lattice relaxation time (T1) of the inorganic phosphate (Pi) resonance is shorter in well-oxygenated than in poorly oxygenated tumors. Amelanotic human melanoma xenografts were therefore subjected to 31P-MRS to investigate whether the T1 of the Pi resonance might be a useful parameter for assessment of tumor oxygenation status. It was searched for possible correlations between the T1 of the Pi resonance and oxygen tension or parameters closely related to oxygen tension, including 31P-MRS tumor energy status and blood supply per viable tumor cell. Oxygen tension, tumor energy status, and blood supply per viable tumor cell decreased with increasing tumor volume. In contrast to previous suggestions, the T1 of the Pi resonance decreased with increasing tumor volume and decreasing oxygen tension, tumor energy status, and blood supply per viable tumor cell, possibly because the tumors developed necrotic regions concomitantly with the decrease in oxygenation status, resulting in increased concentrations of freely dissolved para-magnetic ions in the tissue. Consequently, the T1 of the Pi resonance can probably not be utilized to estimate the oxygenation status of tumors, at least not in tumors with necrotic regions. PMID- 7779421 TI - Distribution of hypoxia and proliferation associated markers in spontaneous canine tumors. AB - The therapeutic response of malignant tumors depends on a number of factors associated with tumor microenvironments including the possibility that these microenvironments change during treatment. Two factors, tumor hypoxia and cell proliferation, have been examined in spontaneous canine tumors undergoing multifraction radiation therapy. The approach utilizes immunohistochemical analyses of hypoxia (CCI-103F) and proliferation associated (PCNA) antigens in biopsy samples taken before and after 5 daily fractions of 3 Gy (total dose 15 Gy). The tissue samples were formalin-fixed and paraffin-embedded for the immunohistochemical study. Immunostaining of the sections for PCNA and hypoxia marker reveals little or no overlap when the analysis is made prior to irradiation. An increased degree of overlap seems to occur after 15 Gy but the situation is complicated by a change towards more diffuse PCNA immunostaining in the cells of the irradiated tissues. PMID- 7779422 TI - Development of bioreductive markers for tumour hypoxia. AB - Hypoxic cells in tumours can be identified by exposing them to an immunologically identifiable 2-nitroimidazole (NITP) with a theophylline substituent which becomes bioreductively metabolised and binds to cellular macromolecules in the absence of oxygen. A range of monoclonal and polyclonal antibodies raised against theophylline or caffeine can identify cells containing bound adducts of NITP, in some cases with higher specificity than the standard product used. An alternative approach utilizes the very high specificity of FITC-avidin as a reagent to detect metabolic binding of a 2-nitroimidazole with a biotinylated side-chain (NIB), with the advantage of a single-step staining protocol. Both proliferating and hypoxic cell populations within tumours can be identified by simultaneous staining for incorporation of NITP and BrdUrd and this has shown that some cells incorporate both markers, suggesting that there is some overlap between the proliferating and hypoxic cell compartments. PMID- 7779423 TI - Characterisation of the vasculature within a murine adenocarcinoma growing in different sites to evaluate the potential of vascular therapies. AB - Numerous vaso-active agents can affect vasculature in experimental solid tumours growing subcutaneously (s.c.), but these models are unlikely to reflect the vasculature of metastatic disease in man. The present study describes a murine orthotopic colon tumour which metastasises to the liver. Morphology and vascular pattern of caecal tumours is similar to s.c. tumours. Vascular occlusion caused by intravenous (i.v.) noradrenaline (NA) (160 micrograms kg-1) and hydralazine (HDZ) (10 mgkg-1) was 32% and 59% respectively for the caecal tumours compared with 35% and 78% for s.c. tumours. Significant morphological differences were seen between liver metastases and systemic deposits produced by i.v. inoculation of tumour cells. Liver metastases following orthotopic transplantation contained functional vasculature but no significant occlusion was seen with NA or HDZ. The vascular development and morphological appearance of secondary disease resulting from orthotopic implantation suggests that this would be a useful model for the study of agents that act either by vascular or anti-angiogenic mechanism. PMID- 7779424 TI - Interstitial fluid pressure in human melanoma xenografts. Relationship to fractional tumor water content, tumor size, and tumor volume-doubling time. AB - The interstitial fluid pressure (IFP) has been shown to be elevated in malignant tissue, but the possibility that IFP might be related to other pathophysiological parameters of the tissue has not been fully explored. The purpose of the study here reported was to measure the IFP in human melanoma xenografts and to search for possible correlations between tumor IFP and fractional tumor water content, tumor wet weight, or tumor volume-doubling time. Tumors of four melanoma lines (A 07, D-12, R-18, U-25), grown orthotopically in BALB/c-nu/nu mice, were included in the study. Tumor IFP, measured by using the wick-in-needle technique, ranged from 2 to 10 mm Hg (D-12), from 2 to 15 mm Hg (A-07 and U-25), and from 2 to 30 mm Hg (R-18). Statistically significant correlations between tumor IFP on the one hand and fractional tumor water content, tumor wet weight, or tumor volume doubling time on the other were not found, whether the tumor lines were analyzed individually or together. These observations suggest that simple general relationships between the IFP and the other pathophysiological parameters measured here, might not exist in tumors. PMID- 7779425 TI - Effect of vasoactive drugs on tumour blood flow as determined by 2H nuclear magnetic resonance spectroscopy. AB - A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half life. PMID- 7779427 TI - Pentoxifylline increases RIF-1 tumour pO2 in a manner compatible with its ability to increase relative tumour perfusion. AB - The time course and dose response of 600 mm3 subcutaneous RIF-1 tumours to pentoxifylline was measured in terms of relative tumour perfusion, assayed by 86Rb extraction, and pO2 distribution measured by the Eppendorf histograph. Both perfusion and pO2 distribution were maximally increased by 20 mg/kg pentoxifylline 15 min after administration, perfusion to 141 +/- 15% (2 SE) of control, and median pO2 from 3 to 15 mmHg, with the percentage of values < 2.5 mmHg falling from 44 +/- 8% to 22 +/- 7%. Fifteen minutes after administration the pO2 increases were linearly dose-dependent up to 20 mg/kg. Correlation coefficients for perfusion data with the percentages of low values were, for time course and dose response data respectively, 0.76 and 0.84 for median pO2, 0.84 and 0.97 for percentage < 2.5 mmHg and 0.81 and 0.87 for percentage < 10 mmHg. The data show good correlation between changes in perfusion and pO2 distribution parameters, with better correlation for percentage of low values than for median pO2. PMID- 7779426 TI - Tumor oxygenation in anemic rats: effects of erythropoietin treatment versus red blood cell transfusion. AB - Anemia was induced in rats by the development of a hemorrhagic ascites. These animals also bore solid tumors (DS-sarcomas) on the hind foot dorsum. The effects of two methods for anemia correction on oxygenation in the solid tumors were compared in this study. Anemia was corrected either chronically by erythropoietin administration (1000 IU/kg) over 14 days (EPO) or acutely by transfusion with red blood cells (TR). Non-anemic and untreated anemic animals served as controls. Tumor oxygenation was determined in anesthetized animals using polarographic needle electrodes and pO2 histography. The reduction in hematocrit and hemoglobin content found in anemic animals could successfully be corrected either by EPO or by TR. Anemia resulted in a worsening of tumor oxygenation which could partially be reversed by EPO or TR in small tumors (< 1.4 ml). In larger tumors (> or = 1.4 ml), neither method of anemia correction resulted in significant changes in tumor oxygenation. PMID- 7779428 TI - Effect of nicotinamide and pentoxifylline on normal tissue and FSA tumor oxygenation. AB - Nicotinamide (NA) and pentoxifylline (PTX) sensitize experimental murine tumors to radiation without sensitizing normal tissues. They are presumed to exert this effect by reducing hypoxia in tumors. The present study evaluated the individual and combined effects of NA and PTX on oxygen levels in subcutaneous normal tissue and subcutaneous FSa fibrosarcoma tumors in the hind foot dorsum of C3H mice. Oxygen measurements were made using a polarographic needle electrode inserted into the tissue immediately before and/or 15-60 min after intraperitoneal administration of 500 mg/kg of NA, 50 mg/kg of PTX, or saline. The median tumor pO2 increased from a mean +/- S.E.M. of 4.1 +/- 1.1 mm Hg in saline-treated control mice to 6.8 +/- 1.9 mm Hg 15 min after NA, 7.6 +/- 1.4 mm Hg 60 min after PTX, and 6.7 +/- 1.1 mm Hg after NA and PTX in combination. PTX raised the median tumor pO2 level from 21% to 39% of the median subcutaneous normal tissue pO2 (p < 0.01). PTX also significantly reduced the proportion of tumor pO2 values < or = 2 mm Hg from 41 +/- 10% to 8 +/- 7% (p = 0.02). Although NA did increase the proportion of tumor that was well oxygenated, it did not significantly reduce the proportion of tumor pO2 values < or = 2 mm Hg (p = 0.34). The combination of NA and PTX did not add to the tumor oxygenation enhancement achieved by PTX alone. NA increased the median subcutaneous normal tissue pO2 by an average of 5.1 +/- 2.2 mm Hg from a baseline of 17.1 +/- 2.2 mm Hg (p = 0.04). PTX had no effect on the median normal tissue pO2 (p = 0.93). PTX showed greater therapeutic potential in this model system than did NA. PMID- 7779429 TI - The modification of blood flow in tumours and their supplying arteries by nicotinamide. AB - We have studied the ability of the radiosensitizer nicotinamide (NA) to alter the contractility of normal and tumour blood vessels using an ex vivo isolated artery perfusion system. NA at a concentration of 8.2 mM reduced the constrictions produced by phenylephrine (PE) by 2-fold in both normal epigastric arteries and those that had been supplying p22 tumours in BD9 rats. At that same concentration NA also attenuated the spontaneous, rhythmic contractions that were seen in many tumour arteries. When the tumour arteries were perfused together with the tumour they supplied NA had little effect on the flow resistance of the tumour vascular network but reduced the resistance by up to 30% when the arteries were preconstricted with phenylephrine. These direct effects on vascular resistance together with the reduction of interstitial fluid pressure could combined to improve the homogeneity of tumour perfusion. PMID- 7779430 TI - The effect of nicotinamide on microregional blood flow within tumours assessed using laser Doppler probes. AB - Laser Doppler probes have been used to provide real-time spatial flow mapping of microregional erythrocyte flux within the murine Sarcoma F (SaF). The results demonstrate that fluctuations in microregional red blood cell flux are a common feature of SaF tumours, with approximately 50% of regions demonstrating a change of at least a factor of 2 over a one-hour sampling period and 16% of regions showing a greater than 5-fold change. Administration of 250 mg/kg nicotinamide induced a small reduction in the number of microregions showing fluctuations, 9% of regions demonstrated large fluctuations (i.e., > or = 5) relative to 16% in control tumours. At a dose of 500 mg/kg, the number of changes in microregional erythrocyte flux was increased. However, unlike either untreated or nicotinamide 250 mg/kg pretreated animals, these changes were mostly increases in microregional flow. Indeed, 12 of the 13 changes by a factor of 5 or greater, observed following nicotinamide at 500 mg/kg, were increases. This effect on microregional flow translated into only a 25% increase in macroregional flow determined by averaging all the regions sampled. PMID- 7779431 TI - The role of tumor volume in 'reoxygenation' upon cyclophosphamide treatment. AB - The effect of cyclophosphamide (CP) injection (60 mg/kg i.p., single dose) on volume growth and tissue oxygenation (pO2 distribution) was investigated in rat DS-sarcomas. CP was administered 4 days after subcutaneous (s.c.) tumor implantation (volume approximately 0.35 ml). Polarographic pO2 measurements were performed in the subcutis at the hind foot dorsum and in tumors 72 h after CP administration. The oxygenation status of these tissues was compared with that of saline-treated controls. CP-injection caused a mean growth delay of 11 days in DS sarcomas and had no impact on the oxygenation status of the subcutis. In contrast, in s.c. growing DS-sarcomas the pO2 distribution improved significantly when treated tumors (0.59 ml volume) were compared with their untreated counterparts (1.15 ml volume). Comparison of the oxygenation data of CP-treated tumors with size-matched controls revealed an identical oxygenation status in the experimental tumors used. Thus, when 'reoxygenation' is discussed, one should consider whether it is solely the result of tumor shrinkage or a volume independent phenomenon. PMID- 7779432 TI - Tumor reoxygenation as a mechanism of taxol-induced enhancement of tumor radioresponse. AB - Paclitaxel is a novel chemotherapeutic agent that arrests cells in the radiosensitive G2 and M phases of the cell cycle and as such may act as a specific cell cycle radiosensitizer. We recently reported that paclitexel induces mitotic arrest in the MCA-4 murine mammary carcinoma and enhances radio-response of this tumor. However, the greatest enhancement was observed not when radiation was given at the time of peak mitotic arrest, which was 9 h after paclitaxel administration, but when it was given 24 h after paclitaxel. This implied the involvement of other mechanisms in radiosensitization; we hypothesized that tumor reoxygenation was a likely mechanism based on the observed massive loss of mitotically arrested cells at 24 h. The present study shows that paclitaxel greatly enhanced MCA-4 tumor radioresponse when radiation was given under air breathing conditions (DMF = 1.74), but not when it was performed under hypoxic conditions. This observation supports the hypothesis of tumor reoxygenation as a mechanism of enhancement of tumor radioresponse. That reoxygenation occurred in tumors treated with paclitaxel 24 h earlier was confirmed by direct measurements of pO2 values, using the Eppendorf pO2 histograph. Median pO2 values increased from 6.2 mmHg in untreated tumors to 10.0 mmHg in tumors treated with paclitaxel. These observations emphasize the importance of timing of paclitaxel administration in relation to radiation treatment. PMID- 7779433 TI - Interaction between ionizing radiation, estrogens and antiestrogens in the modification of tumor microenvironment in estrogen dependent multicellular spheroids. AB - MCF7 human breast cancer cells growing as multicellular spheroids were examined as a model of three-dimensional cellular organization. Estrogen-free medium inhibited spheroid formation. In medium containing estrogens, the antiestrogen hydroxytamoxifen decreased the spheroid growth rate. Analyses with the recursion formula after Gompertz fitting showed that the rate of exponential decrease in growth rate (alpha) was alpha 0.099 +/- 0.013 d-1, and the decrease in alpha' was 0.061 +/- 0.015 d-1 for 0.1 microM hydroxytamoxifen and control spheroids respectively. MCF7 cells which had been growth arrested in an estrogen-free medium showed a significant decrease in radiosensitivity (surviving fraction at 2 Gy, SF2 = 63%) when compared with 0.1 nM 17 beta-estradiol-treated cells (SF2 = 38%). No differences in radiosensitivity were seen in MCF7 spheroids in estrogen supplemented medium (radiation dose necessary to control 50% of spheroids (SCD50) was 5.51 Gy; derived alpha, beta and SF2 were 0.301 +/- 0.110 Gy-1, 0.018 +/- 0.005 Gy-2, and 51% respectively) when compared with monolayer cultures in the same medium (alpha = 0.316 +/- 0.059 Gy-1, beta = 0.023 +/- 0.006 Gy-2 and SF2 = 50%). In the spheroid model, manipulating the cellular environment, i.e., with estrogen treatment, modulates sensitivity to ionizing radiation. PMID- 7779434 TI - Effect of intraperitoneal ATP on tumor growth and bone marrow radiation tolerance. AB - Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal ATP were studied in vitro, and in both C3H and nu/nu mice. Daily ATP treatment prolonged tumor volume doubling time in vivo and in vitro. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH or the PCr/Pi, or beta ATP/Pi ratios (measured by MRS). In contrast to the reduced tumor growth rate, there was no change in bone marrow recovery after whole body irradiation. ATP is minimally toxic to animals at active dose levels. It slows tumor growth rate without adversely affecting bone marrow radiation tolerance. ATP might therefore be useful as a biological modifier of chemotherapy or radiation therapy. PMID- 7779435 TI - Cytotoxic effect of tumour necrosis factor -alpha on sarcoma F cells at tumour relevant oxygen tensions. AB - We have investigated the response of a murine tumour cell line, the sarcoma F (SaF), to tumour necrosis factor-alpha (TNF) at oxygen tensions known to occur in vivo. Using the Eppendorf pO2 histograph, the oxygen status of SaF tumours grown in situ was assessed. The median pO2 of the SaF is less than 1% oxygen with over 90% of values at or below 15 mmHg (< 2% O2). SaF cells primed in vitro for 24 h at tumour relevant oxygen tensions required at least four times more TNF to reduce cell number to 50% of controls following a 24 h incubation period in 21% oxygen. Chronic exposure of SaF cells to hypoxia during several passages increased resistance to TNF more than 60-fold. The oxygen sensitizing effect is transient as the resistance of hypoxic cells to TNF was reversed after 24 h incubation in air. These data clearly show that oxygen tension is a key modulator of the cytotoxic action of this important cytokine. PMID- 7779436 TI - Modification of tumour glucose metabolism for therapeutic benefit. AB - Tumours have a much greater dependence than normal tissues on anaerobic glycolysis for energy generation. We have studied the effects of glycolysis inhibition on tumour cells in vitro. Cellular ATP fell during exposure of cells in air to 2-deoxy glucose or to the lactate dehydrogenase inhibitor oxamate. Glycolysis inhibition alone did not alter clonogenic cell survival over 6 h, but a 6-h exposure to oxamate combined with doxorubicin (Dox) gave greater than additive cell killing. This effect was greatest when oxamate was dosed after Dox, suggesting that oxamate inhibited repair of Dox-induced damage. Oxamate also gave greater than additive cell killing in multicellular spheroids when combined with Dox and there was a greater than additive growth delay in spheroids dosed with Dox plus oxamate. These data demonstrate that inhibition of anaerobic glycolysis might be used to obtain a significant therapeutic gain in combination treatments with cytotoxic drugs or radiotherapy. PMID- 7779437 TI - Basic fibroblast growth factor radioprotects bone marrow and not RIF1 tumor. AB - We examined the potential of bFGF to function as a radioprotector of bone marrow (BM). Total intravenous doses of bFGF ranged from 1 to 24 micrograms/mouse, in 2 divided doses. Whole body radiation (WBI) was given in a single fraction to C3H mice. Histologic observations were performed on femur BM at various times after bFGF (or placebo) treatment. Thigh radiation in thigh-tumor bearing mice was delivered in a single fraction. bFGF increased the LD50/30 of mice in a dose dependent fashion, with an apparent maximum protection obtained with > or = 6 micrograms given half 24 h and half 4 h before irradiation. BM histology shows prominent recovery of megakaryocytes and all cell lineages along with less loss in cellularity compared to control irradiated animals. No radioprotection of RIF1 tumors after bFGF was detected. These results indicate that bFGF may be a selective radioprotector of normal tissue. PMID- 7779438 TI - Modification of tumor microenvironment by cytokine gene transfer. AB - The tumor microenvironment is determined by the interactions between host and tumor cells, a process in which cytokines play a major role. We have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells that infiltrate tumors. This frequently caused changes in tumor cell phenotype through autocrine/intracrine pathways. We reasoned that cytokine-induced alterations in tumor cell phenotype and/or in infiltrating host cells might alter the in vitro and in vivo cellular response to irradiation. In the present paper we document some of the effects of expression of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this regard. The studies support the hypothesis that cytokines may play a role in determining both intrinsic tumor radioresponsiveness and the tumor microenvironment and in these ways may influence in vivo tumor irradiation responses. Possible cytokine gene-mediated approaches to radiotherapy cancer are discussed. PMID- 7779439 TI - Protection against inhalation toxicity of ricin and abrin by immunisation. AB - 1. Abrin and ricin are highly toxic plant proteins which are very similar in structure and function and inhibit protein synthesis in eukaryotes. 2. Rats have been immunised against either toxin using formaldehyde-toxoids by three subcutaneous injections at intervals of 3 weeks. For abrin, serum titres in 14 out of 15 rats were raised to between 1:12800 and 1:51200 after two injections, 6 weeks from the start of the experiment. Titres of between 1:256 and 1:1024 were also measured in lung washes after challenge with active abrin toxin. 3. The three major antibody classes, IgG, IgM and IgA were present in the immune sera but IgG and IgA only were detected in lung washes. The proportion of IgA to IgG was higher in the lung fluid than in sera. Rats immunised by abrin toxoid were protected against 5 LCt50's of abrin by inhalation but others exposed to ricin were not. 4. For ricin, serum titres ranged from 1:800 to 1:25600 after two injections and after a third injection the titre range was the same but population samples were weighted towards the higher titres. All rats immunised with ricin toxoid survived the challenge of 5 LCt50's of ricin toxin by inhalation over the observation period of 28 days post-challenge. 5. Representative immunised rats (abrin toxoid) were taken at various times post exposure, humanely killed and tissues were examined for pathological changes. It was concluded that an apparently severe lung lesion occurred at a later time than in non-immunised, toxin challenged rats. This damage was not lethal over the experimental observation periods. 6. Immunisation by the sub-cutaneous route therefore protects against lethality from challenge by inhalation of ricin or abrin toxins but does not prevent significant lung damage. PMID- 7779440 TI - Decorporation of thorium-228 from the rat by 3,4,3-LIHOPO and DTPA after simulated wound contamination. AB - 1. With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treatment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2. In all cases 3,4,3-LIHOPO was appreciably more effective than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3. Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body content of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The corresponding values using repeated DTPA administration were 80% and 54%. 4. It is concluded that 3,4,3-LIHOPO represents, potentially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contaminated by 228Th. PMID- 7779441 TI - Prevention of drug absorption in simulated theophylline overdose. AB - 1. The effects of emesis, gastric lavage and oral activated charcoal on theophylline absorption were compared in healthy volunteers. 2. One of four regimes (ipecacuanha-induced emesis, gastric lavage, oral activated charcoal and no treatment) was randomly chosen one hour after a simulated overdose with sustained-release theophylline on four separate occasions in twelve healthy volunteers. 3. Syrup of ipecacuanha produced emesis in all twelve volunteers but only seven vomited any tablets. Gastric lavage yielded tablets in only one volunteer. 4. The mean systemic availabilities (areas under the concentration time curves relative to control) of theophylline for ipecacuanha-induced emesis, gastric lavage and charcoal, were 107.1%, 101.1% and 16.9%, respectively. 5. Oral activated charcoal was thus highly effective, while gastric lavage and emesis were ineffective in preventing theophylline absorption. Activated charcoal is potentially the most effective first-line treatment for acute overdosage with sustained-release theophylline tablets. PMID- 7779442 TI - Setting air quality standards for carcinogens: an alternative to mathematical quantitative risk assessment--discussion paper. AB - 1. It has been accepted in many countries that the regulation of ambient air quality should involve the use of health-based air quality standards. 2. Setting standards for air pollutants which are genotoxic carcinogens presents difficult problems to the regulator, in that the prediction of the effects on health of low levels of exposure is suspected to be inaccurate, and is not presently amenable to either experimental or epidemiological verification. 3. In some countries, techniques of Mathematical Quantitative Risk Assessment (MQRA) have been adopted to calculate acceptable levels of exposure to, or the unit risk factors for, genotoxic carcinogens. We regard these approaches as unsatisfactory. 4. An alternative approach, based upon a number of argued premises, a strategy which identifies decision points and the cautious application of uncertainty factors, is described. PMID- 7779443 TI - The clinical value of screening for paracetamol in patients with acute poisoning. AB - In this retrospective study, we determined the clinical value of screening for paracetamol in 294 Chinese patients with acute poisoning presenting to the general medical wards at the Prince of Wales Hospital between January 1992 and June 1993. Of the 86 patients suspected of having ingested paracetamol, eight had levels above the recommended 'treatment line'. Of the 208 patients with no suspected paracetamol ingestion, four were found to have elevated but non-toxic plasma levels. The incidence of missed, potentially serious paracetamol poisoning in our patients with no suspected paracetamol ingestion is extremely uncommon. Routine screening of all patients with acute poisoning for toxic plasma paracetamol concentrations is therefore not indicated and should never be a substitute for thorough history taking and physical examination. PMID- 7779444 TI - The risk of aspiration in Dettol poisoning: a retrospective cohort study. AB - 1. To determine if the risk of aspiration is increased in 'Dettol' (4.8% chloroxylenol, pine oil and isopropyl alcohol) poisoning and the factors that may be responsible, a study was made of 89 patients and 89 matched control subjects with other forms of poisoning admitted to the Prince of Wales Hospital, Hong Kong. 2. Aspiration was more common in patients with Dettol poisoning (8% vs 3%, P = 0.16). There were more control subjects with drowsiness at presentation (54% vs 24%, P < 0.0001), but the use of gastric lavage (88% vs 64%, P < 0.001) and the occurrence of vomiting (62% vs 17%, P < 0.0001) were more common in patients with Dettol poisoning. 3. Our findings suggest that Dettol poisoning may be associated with an increased risk of aspiration. This increase in risk may be related to the use of gastric lavage and the common occurrence of vomiting in patients with Dettol poisoning. PMID- 7779445 TI - Continuous intravenous infusion in the unrestrained rat--procedures and results. AB - 1. A method of continuous infusion in the unrestrained rat is described, which provides a scientifically acceptable and easily maintained rodent model for use in toxicological investigations. 2. Sprague Dawley SPF rats had cannulas implanted into the vena cava via the femoral vein, and were continuously infused with physiological saline for a total of 28 or 90 days. 3. The results indicate that there was no change in body weight, food consumption, clinical observations or clinical biochemistry of infused rats when compared to non-infused rats. There were small changes in haematological parameters, however none were toxicologically significant. Urinary volume was increased and urinary specific gravity and osmolality were decreased. At macroscopic and microscopic examination there were findings of scar formation associated with the area of surgery and minimal irritation in the area of the vena cava which accommodated the cannula. 4. These results indicate that implantation of a cannula into the vena cava of a rat and subsequent continuous intravenous infusion of physiological saline produces no toxicological adverse effects over a period of 90 days. Consequently, this model can be recommended for the continuous intravenous administration of test substances to rats. PMID- 7779447 TI - A stepwise procedure for evaluating irritant materials in normal volunteer subjects. AB - 1. The cutaneous response to a known irritant has been assessed in human volunteer subjects using both clinical scoring and two non-invasive instrumental methods; erythema measurement using an erythema meter and capillary blood flow using a laser Doppler device. 2. Aqueous solutions (0.5% and 1%) of sodium hydroxide were applied to back skin for 3, 15 and 60 min with assessments immediately after removal and at 1, 24 and 48 hours. 3. Increased erythema was seen with increasing duration of exposure and an increase was also seen at 1 h, 24 h and 48 h after removal of the patch. The results obtained with the erythema meter paralleled the clinical erythema scores. However, the laser Doppler device showed the greatest changes immediately after removal of the patch with subsequent readings showing a gradual decrease. 4. Statistical analysis of the data has been carried out to determine the accuracy and precision of the assessment procedures and to determine the minimum test panel size for detecting irritant reactions. 5. Comparison between back and forearm skin indicated a greater sensitivity to sodium hydroxide on the back. 6. The results of this study define an ethical approach to testing irritant materials in human subjects and provide the basis for the development of a classification system for cutaneous irritants. PMID- 7779450 TI - Old enzymes in new roles. PMID- 7779448 TI - Persistence of sodium monofluoroacetate in rabbits and risk to non-target species. AB - 1. Sodium monofluoroacetate (1080), a vertebrate pesticide used in New Zealand, was administered orally to rabbits at two dose levels (sub-lethal and lethal) to determine how long 1080 would persist in plasma, liver, kidney, and muscle so that the risk of consumption of meat from lethally or sub-lethally poisoned rabbits by non-target species could be assessed. 2. The plasma elimination half life in rabbits receiving a sub-lethal dose was 1.1 h. Retention of 1080 in tissue was greater in rabbits dosed with a lethal dose than in those that received a sub-lethal dose. Irrespective of the dose level, concentration of 1080 in muscle, kidney, and liver was substantially lower than in the plasma. 3. Poisoning of dogs is possible because of their extreme susceptibility to 1080. Poisoning of birds is less likely. The risk of secondary poisoning is reduced as the concentration of 1080 declines in putrefying carcasses. PMID- 7779451 TI - To pop or not to pop: p53 as a critical modulator of tumour responsiveness to therapy in vivo? PMID- 7779449 TI - A comparison of the acute pathology induced by 3-phenylamino-1,2-propanediol (PAP) and its mono-oleoyl ester in rodents with the toxic oil syndrome in man. AB - Phenylamino-1,2 propanediol (PAP) and its mono-oleoyl ester have been identified in samples of the cooking oil thought to be responsible for the Toxic Oil Syndrome (TOS) which occurred in Spain in 1981. The acute toxicity of PAP and its mono-oleoyl ester have been examined in rats and mice, after daily administration for periods of up to 14 days to determine whether these compounds could produce any of the pathologies of TOS. Even at the highest dose, the 1-mono-oleoyl ester of 3-phenylamino-1,2 propanediol did not cause any toxicity in rats or mice when given intraperitoneally. 3-Phenylamino-1,2 propanediol, however, was toxic when administered to rats by this route. After 6-10 consecutive daily doses of PAP, at the highest dose administered (350 mg kg-1), all of the rats became unwell. Postmortem examination showed that the major pathology present was massive pulmonary thromboembolism. Further investigations of the toxicity of PAP after intravenous administration showed that it was not directly vasotoxic. The pulmonary thromboembolism seen with intraperitoneally administered PAP was due to the toxic effect of PAP on the mesenteric tissue and blood vessels, causing thrombosis which subsequently embolised the blood vessels in the lung. Intra gastric administration of PAP caused no toxicity in rats. Comparatively, the pathology seen after intraperitoneal administration of PAP was not thought to be representative of the pathology of the toxic oil syndrome in man. PMID- 7779446 TI - Effects of variation in detoxification rate on dose monitoring through adducts. AB - 1. Fost et al. (Human & Experimental Toxicology 1991; 10: 25) have shown that ethylene oxide (EO) added to human blood gave rise to a higher level of adducts to haemoglobin (Hb) when the donors were deficient in an erythrocytic glutathione S-transferase (GST, later found to be GST-theta) than in blood from persons possessing this enzyme, and drew the conclusion that this polymorphism in detoxification rendered Hb adducts less suitable for biological monitoring. 2. By fitting a kinetic model to the data, the present study shows that the Hb adduct level gives a correct measure of the dose (concentration integrated over time) relevant to risk estimation. 3. It does illustrate, however, the importance of knowing an individual's detoxification efficiency, when Hb adduct measurements are used to assess environmental exposure, for example in occupational surveillance. PMID- 7779452 TI - The ying-yang of RAR and AP-1: cancer treatment without overt toxicity. PMID- 7779453 TI - Apoptosis: regulation and relevance to toxicology. AB - 1. Apoptosis is a remarkably stereotyped morphological event across all tissues in response to a vast array of damaging agents. 2. Our very existence depends upon a willing exchange of old life for new: apoptotic cell death is our guardian and saviour from genetic damage. 3. There is a close link between cell proliferation and apoptosis: When a cell picks up the machinery to proliferate it also acquires an abort pathway--'better dead than wrong'. 4. A wide variety of highly conserved genes have been implicated in triggering apoptosis. 5. The release of DNA loops from the nuclear scaffold is a more crucial intracellular event than DNA 'laddering' in apoptotic cells. 6. The manipulation of apoptotic rates in many of the common diseases in man will be a major therapeutic strategy in the future. PMID- 7779455 TI - Sarin-induced neuropathology in rats. AB - Sarin, a highly toxic cholinesterase (ChE) inhibitor, administered at near 1 LD50 dose causes severe signs of toxic cholinergic hyperactivity in both the peripheral and central nervous systems (CNS). The present study evaluated acute and long-term neuropathology following exposure to a single LD50 dose of sarin and compared it to lesions caused by equipotent doses of soman described previously. Rats surviving 1 LD50 dose of sarin (95 micrograms/kg; IM), were sacrificed at different time intervals post exposure (4 h-90 days) and their brains were taken for histological and morphometric study. Lesions of varying degrees of severity were found in about 70% of the animals, mainly in the hippocampus, piriform cortex, and thalamus. The damage was exacerbated with time and at three months post exposure, it extended to regions which were not initially affected. Morphometric analysis revealed a significant decline in the area of CA1 and CA3 hippocampal cells as well as in the number of CA1 cells. The neuropathological findings, although generally similar to those described following 1 LD50 soman, differed in some features, unique to each compound, for example, frontal cortex damage was specific to soman poisoning. It is concluded that sarin has a potent acute and long-term central neurotoxicity, which must be considered in the design of therapeutic regimes. PMID- 7779454 TI - Superoxide radical and toxicity of environmental nickel exposure. AB - Three nickel compounds were tested for pancreatic, hepatic and osteogenic damage in rats by a single i.m. injection Ni++ (7 mg kg-1). The nickel induced biochemical alterations included significantly increased levels of serum alkaline phosphatase in rats with NiS (75%) and NiO (50%). Amylase and aspartate transaminase were also increased, and lipoperoxide was increased in rats with NiO (5.6-fold) and NiS (3.4-fold). No serum changes were observed with NiCl2. Daily injection of Cu-Zn superoxide dismutase (SOD) conjugated with polyethylene glycol prevented the serum level changes, indicating that superoxide radical is an important intermediate in toxicity of nickel insoluble compounds. PMID- 7779456 TI - In vitro and in vivo percutaneous absorption of 14C-chloroform in humans. AB - Chloroform has been found in potable water and there is concern that significant dermal absorption may arise from daily bathing and other activities. The present study examines percutaneous absorption of 14C-chloroform in vivo using human volunteers and in vitro using fresh, excised human skin in a flow-through diffusion cell system. Fifty microlitre doses of either 1000 micrograms ml-1 chloroform in distilled water, (16.1 micrograms cm-2) or 5000 micrograms ml-1 of chloroform in ethanol, (80.6 micrograms cm-1) were applied to the forearm of volunteers with exhaled air and urine being collected for analysis. Single doses of either 0.4 microgram ml-1 chloroform in distilled water (low dose, 0.62 microgram cm-2, 1.0 ml dosed) or 900 micrograms ml-1 chloroform in distilled water (high dose, 70.3 micrograms cm-2, 50 microliters dosed) were applied to discs of the excised abdominal skin placed in flow-through diffusion cells and perfused with Hepes buffered Hank's balanced salt solution, with a wash at 4 h. In vivo absorption was 7.8 +/- 1.4% (water as vehicle) and 1.6 +/- 0.3% (ethanol as vehicle). Of the dose absorbed in vivo, more than 95% was excreted via the lungs (over 88% of which was CO2), and the maximum pulmonary excretion occurred between 15 min and 2 h after dosing. The percentage of dose absorbed in vitro (skin+perfusate) was 5.6 +/- 2.7% (low dose) and 7.1 +/- 1.4% (high dose). The above data demonstrate that a significant amount of the dissolved chloroform penetrates through the human skin, and that a higher percentage of the applied dose was absorbed using water as vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779457 TI - Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leukocytes by particulate stimuli. AB - 1. A new specific protein kinase C (PKC) inhibitor, Ro 31-7549, was used to explore the mechanisms by which particulate stimuli, quartz and chrysotile, stimulate human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM). Also soluble stimuli, formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and phorbol myristate acetate (PMA) were used. 2. Ro 31-7549 inhibited chrysotile-induced free intracellular calcium ([Ca2+]i) elevations but did not have an effect on quartz-induced elevations of [Ca2+]i. Both quartz and chrysotile induced production of ROM were partially inhibited by Ro 31-7549. fMLP induced elevation of [Ca2+]i was inhibited by Ro 31-7549 whereas PMA did not affect [Ca2+]i. Ro 31-7549 strongly inhibited fMLP-induced ROM production, and completely abolished that induced by PMA. 3. These result suggest that PKC may have an important role in the activation of PMNL to produce ROM by particulate and soluble stimuli. However, the inhibition of chrysotile-, but not of quartz induced [Ca2+]i elevations by Ro 31-7549 provides evidence that both PKC dependent and -independent mechanisms may play a role in the activation of human leukocytes to produce ROM. PMID- 7779458 TI - A biologically-based algorithm for predicting human tissue: blood partition coefficients of organic chemicals. AB - A biologically-based algorithm for predicting the tissue: blood partition coefficients (PCs) of organic chemicals has been developed. The approach consisted of (i) describing tissues and blood in terms of their neutral lipid, phospholipid, and water contents, (ii) obtaining data on the solubility of chemicals in n-octanol and water, and (iii) calculating the tissue: blood PCs by assuming that the solubility of a chemical in n-octanol corresponds to its solubility in neutral lipids, the solubility in water corresponds to the solubility in tissue/blood water fraction, and the solubility in phospholipids is a function of solubility in water and n-octanol. The adequacy of this approach was verified by comparing the predicted values with previously published experimental data on human tissue (liver, lung, muscle, kidney, brain, adipose tissue): blood PCs for 23 organic chemicals. In the case of liver, lung, and muscle, the predicted PC values were in close agreement with the higher-end of the range of experimental PC values found in the literature. The predicted brain: and kidney: blood PCs were greater than the experimental PCs in most cases by approximately a factor of two. Whereas the adipose tissue: blood PCs of relatively less hydrophilic chemicals were adequately predicted, the predicted PCs for relatively more hydrophilic chemicals were much greater than the experimentally-determined values. There was a good agreement between the predicted and experimentally-determined blood solubility of the 23 chemicals chosen for this study, indicating that the over-estimation of tissue:blood PCs by the present method is not due to under-estimation of blood solubility of chemicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779459 TI - Measurement of the respiratory burst and chemotaxis in polymorphonuclear leukocytes from mercury-exposed workers. AB - The chemotactic and nitroblue tetrazolium reducing activities of neutrophils from 48 mercury-exposed workers were examined and compared with those of non-exposed, age- and sex-matched individuals. At the time of testing, the exposed population had a mean (+/- s.d.) urinary mercury concentration of 24.0 +/- 20.1 micrograms g 1 creatinine and in 44 of these workers urinary mercury levels were below the accepted threshold level (TLV) of 50 micrograms g-1 creatinine. The two neutrophil functions were significantly reduced in the mercury-exposed workers compared with the controls. In 28 of these workers, chemotaxis was re-evaluated 6 months later. During the intervening 6 months, the level of hygiene was improved throughout the plant and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, neutrophil migration did not return to within the normal range. These results suggest that 'safe' level mercury exposure may lead to impairment of neutrophil function. PMID- 7779460 TI - Human metabolism of aluminium-26 and gallium-67 injected as citrates. AB - 1. 26Al and 67Ga were given as citrates to a healthy male volunteer by intravenous injection. The retention of both tracers was studied by body radioactivity measurement. Levels in blood and excreta were determined by gamma ray spectrometry and/or accelerator mass spectrometry. 2. More than half of the 26Al had left the blood after 15 min and the decline continued, leaving < 1% in blood after 2 d; the losses occurred both to renal excretion and through uptake by other compartments. Estimated excretion up to 13 d was 83% (urine) and 1.8% (faeces). Whole-body retention of 15% at 13 d declined to approximately 4% at 1178 d, when the daily reduction corresponded to a biological half-life of 7 y, suggesting that sustained intake of dietary aluminium may lead to a progressively increasing internal deposit. 3. The metabolism of 67Ga differed markedly from that of 26Al in all aspects studied. PMID- 7779461 TI - Amisulpride poisoning: a report on two cases. AB - The first two observations of human poisoning involving the recently developed neuroleptic amisulpride are described. In both cases drug determination was performed using reversed-phase HPLC coupled with diode array detection. Case 1 was a nonfatal overdosage in which the ingestion of 3.0 g amisulpride induced an attack of seizures, then light coma with agitation, hyperthermia, mydriasis, minimal extrapyramidal features, tachycardia and slight prolongation of the QT interval; the blood concentration of amisulpride was 9.63 micrograms ml-1. Case 2 was a fatality attributed to amisulpride in which the measured blood concentration was 41.70 micrograms ml-1. Our results are discussed in the light of data previously reported on the toxicity of substituted benzamides. PMID- 7779462 TI - Cimetidine as adjunctive treatment for acetaminophen overdose. AB - The aim of this study was to determine if cimetidine in addition to N acetylcysteine and standard supportive care provide additional hepatoprotection following acute acetaminophen poisoning. It was designed as a prospective study with alternate month treatment protocol, and the work was carried out at a regional certified poison information centre. For a 2-year period, consultations received by the Rocky Mountain Poison Center involving acute acetaminophen overdose patients with a serum level above the nomogram line, but who would not receive N-acetylcystine therapy until at least 8 h postingestion, were prospectively evaluated for adjunctive treatment with cimetidine. All patients received standard supportive therapy and N-acetylcysteine treatment. During odd numbered months, cimetidine 300 mg was administered intravenously every 6 h for the duration of N-acetylcysteine therapy. Forty-one cimetidine treated patients were compared to 66 patients in the control group. The peak measured AST levels (+/- s.e.) were 1259+/-330 and 1301+/-451 for the control and cimetidine treatment groups, respectively (P = 0.94). Fourteen of 64 patients (21%) in the control group and 8/41 patients (20%) in the cimetidine group developed an AST > 1000 IUL-1. There were no statistical differences between the cimetidine-treated and control groups when classified by AST < 100 IUL-1, 100-1000 IUL-1, or > 1000 IUL-1. The addition of cimetidine therapy to standard N-acetylcysteine treatment did not provide additional hepatoprotection in acutely acetaminophen poisoned patients when treatment was started later than 8 h post overdose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779463 TI - Guideline limit volumes for dosing animals in the preclinical stage of safety evaluation. Toxicology Subcommittee of the Association of the British Pharmaceutical Industry. AB - Guideline limit volumes for dosing laboratory animals by oral and parenteral routes in the preclinical stage of safety evaluation were agreed following discussions by the Toxicology Subcommittee of the Association of the British Pharmaceutical Industry. The guideline values represent common practice rather than absolute maxima. Whilst the guideline values are expected to be of value to scientists and technical staff involved in study design and applicable to the majority of routine safety evaluation studies, scope remains to make the case for special investigations. The need to carefully consider animal welfare and physiology, current legislation, the use of appropriate dosing technology and formulations, and other practical aspects of study conduct, is emphasised. PMID- 7779464 TI - NO wonder paraquat is toxic. PMID- 7779465 TI - The good, the bad and the ugly of T-cell selection in the thymus. PMID- 7779466 TI - Arty-crafty fact of life? PMID- 7779467 TI - Isolation of renal multidrug transporter. PMID- 7779468 TI - General practitioners' tacit and stated policies in the prescription of lipid lowering agents. AB - BACKGROUND: Research into general practitioners' prescribing behaviour with regard to lipid lowering agents has relied on survey methods which presume that doctors have insight into their prescribing behaviour and can describe it accurately. AIM: This study set out to measure the tacit policies used by general practitioners in prescribing lipid lowering agents and to compare these with their stated policies. METHOD: Effects of 13 separate cues on decisions to prescribe were examined. The cues included cholesterol levels and a number of associated risk factors for coronary heart disease. Doctors rated 130 imaginary cases presented by a computer. Thirty five general practitioners in the Plymouth area participated in the study. Their ages ranged from 31 to 55 years and all but four were men. The raw data in each case was a rating of the likelihood that the doctor would prescribe for the patient described. These were converted into statistical weightings by use of multiple linear regression. The pattern of (standardized) weights constituted the tacit policy for each doctor. Stated policies were measured in a subsequent interview by asking doctors to rate the influence of each cue. RESULTS: Both tacit and stated policies diverged widely between different doctors. Most doctors overestimated the number of cues that had actually influenced their decisions, and many believed that they had taken into account associated factors for coronary heart disease when they had not. On lifestyle related risks doctors were generally less likely to treat overweight people and most stated this as their policy. Most were also less likely to treat smokers but some had the opposite policy. Those less likely to treat smokers were also less likely to treat obese patients. There was also considerable variation in the extent to which the doctors took account of the attitude of the patient to receiving treatment. CONCLUSION: Doctors' policies are highly variable and particularly inconsistent in the treatment of smokers. Relevant risk factors may be ignored--even though they are understood--because the risk assessment involved is too psychologically complex a task to be performed intuitively. Decision aids and clear protocols are needed in this area. PMID- 7779469 TI - Should medical students learn more about management? PMID- 7779470 TI - Use of blood tests in general practice: a collaborative study in eight European countries. Eurosentinel Study Group. AB - BACKGROUND: Laboratory tests are routine examinations in general practice and are associated with increasing costs in industrialized countries. AIM: The objective of this collaborative study was to determine the differences in general practitioners' use of blood tests in different European countries and to evaluate the relationship between these differences and organizational aspects of the health care system and also characteristics of the participating general practices. METHOD: A descriptive study was conducted by eight European sentinel networks. Voluntary participating general practitioners registered all blood tests requested for four weeks, specifying the type of test, and age group and sex of patients. Details of all face-to-face encounters with patients by age group and sex were collected for the same period. Information on the participating practices and general practitioners was collected by questionnaire. RESULTS: The request rate for blood tests varied considerably between countries. The characteristics of general practitioners and practice were only slightly or were not associated with the use of blood tests while dummy 'country' variables were strongly associated. The number of general practitioners per 1000 inhabitants was the most positively associated variable partly explaining the intercountry variation. CONCLUSION: This European study suggests that some national characteristics of the health system could determine the use of blood tests in general practice and underlines the need for further investigation in order to develop successful strategies for promoting the optimal use of diagnostic technology. PMID- 7779471 TI - Health care sought and received by men with urinary symptoms, and their views on prostatectomy. AB - BACKGROUND: Urinary symptoms are common among middle aged and elderly men. AIM: A study was undertaken to describe the health care sought by men aged 55 years and over with urinary symptoms, the action taken by general practitioners and urologists, and the men's views on prostatectomy. METHOD: A postal questionnaire was sent to 516 men aged 55 years and over in the North West Thames Regional Health Authority, with previously identified mild, moderate or severe urinary symptoms. RESULTS: The response rate among eligible subjects was 83%. Of 420 respondents 45% had seen their general practitioner for their symptoms. General practitioners had referred 62% of these men to a urologist, reassured 21% and prescribed medication to 17%. The probability of a man seeking medical advice increased with increasing symptom severity. In contrast, the decision to refer was independent of symptom severity. Of the men referred to a urologist, the majority (71%) were offered and accepted surgery. The remainder were reassured (17%), or received a prescription (4%). Eight per cent were offered surgery but declined. When presented with details and information on the risks and benefits of prostatectomy, 22% of men with symptoms would probably or definitely refuse treatment, while a further 47% of men were unsure. CONCLUSION: There are many men who do not seek treatment for urinary symptoms and, of those who do, subsequent referral is not associated with symptom severity. There is scope for improving the referral process through the shared development of guidelines between general practitioners, hospitals and commissioning agencies. PMID- 7779472 TI - Living up to expectations? PMID- 7779473 TI - One counsellor, two practices: report of a pilot scheme in Cambridgeshire. AB - BACKGROUND: Despite limited evidence of their effectiveness, counsellors are increasingly being employed as part of the primary health care team. Evaluation of counsellor services is therefore important. AIM: In 1990 the Cambridgeshire Family Health Services Authority initiated a pilot scheme to evaluate the role of counsellors in general practice and to help the authority determine its policy towards claims by general practitioners for reimbursement through the ancillary staff scheme. METHOD: Two group practices were identified and an external evaluator appointed. The evaluator and the general practitioners developed their aims and objectives for counselling in the general practice context, the number of counsellor hours per week and the type and process of referral. An experienced counsellor was appointed to work in both practices. Information was gathered over two years about doctors' reasons for referral, counsellor's initial assessment, patient outcome at the end of treatment, the patients' and practice teams' opinions about the counselling service, and patient outcome a year after counselling. RESULTS: A total of 293 patients were referred in the first two years of the scheme, of whom 75% were women. The main reasons for referral were that the general practitioners considered the patients to be suffering from anxiety/stress (33%), interpersonal difficulties (33%) and depression (20%). Almost all referrals (98%) were considered by the counsellor to be appropriate. The counsellor was able to provide an assessment for the 248 patients who attended and either take on the case for short-term counselling (69%) or suggest referral to a more appropriate service (25%) (6% withdrew). The expected maximum of six sessions of 45 minutes duration per referral was achieved in 87% of cases. The service was valued by patients and doctors. It coped effectively with a high proportion of patients with problems who did not reappear as demand elsewhere in the practice, and achieved a reduction in dose of psychotropic drugs among those seen. CONCLUSION: This study has shown the value of clarifying referral criteria and the intended role of the counsellor prior to the counsellor's introduction. This ensures effective use of a scarce resource and a high level of satisfaction among doctors and patients. PMID- 7779474 TI - Practice nurse workload before and after the introduction of the 1990 contract for general practitioners. AB - BACKGROUND: A study of practice nurse workload in 1989 by the East Anglian reporting system revealed that nurses were undertaking a wide range of activities, with 12% of nursing time being spent on administration. The 1990 contract for general practitioners emphasized the role of general practice in health promotion. AIM: The 1989 study was repeated by the East Anglian reporting system in 1992 to investigate changes in practice nurse workload. METHOD: Nurses in 22 practices recorded all the procedures they performed and their duration, over a two week period. RESULTS: The number of practice nurses in each practice had increased from 0.7 full time equivalents in 1989 to 1.2 in 1992. The proportion of time spent on administration had increased to 19%. The number of different procedures performed by practice nurses had risen from 36 in 1989 to 54 in 1992, with most new activity in well person and new patient clinics. CONCLUSION: Changes have taken place in the volume and range of work undertaken by practice nurses. There is potential for practice nurses to use the results both for negotiation and for education. PMID- 7779476 TI - Audit as part of summative assessment of vocational training. AB - Written evidence of the ability to carry out audit and performance review looks likely to be one of the four components of a summative assessment package for the end of vocational training. This paper seeks to raise the issues involved in this process. The features of audit which lend themselves to assessment of the attributes of a general practitioner are discussed. The criteria which might be used to assess a written submission are presented. A possible mechanism for marking and grading is suggested, and strategies for optimizing the validity and reliability of that assessment discussed. A timescale for implementation is also suggested. These issues need to be discussed and a process piloted if a credible mechanism is to be in place by August 1996. PMID- 7779475 TI - Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials. AB - Although a number of randomized controlled trials of treatment for herpes zoster have been performed, there is no consensus on how it should be managed in general practice. A systematic review of existing trials, including meta-analysis, was performed to determine the efficacy of available therapies in reducing the incidence of postherpetic neuralgia. The treatments studied included antiviral agents, corticosteroids and other drugs which had been studied in randomized trials. Trials were included if the subjects were immunocompetent adults and the intervention was feasible in general practice. The main outcome measure was prevalence of pain at one, three and six months after onset of the acute herpetic rash. Data for each time point were not available for all trials. The quality of studies was also assessed. Pooled analyses of trials with acyclovir failed to detect a significant reduction of pain in the treatment group at one or six months, but found a 35% reduction at three months. Confidence limits were wide, and a modest benefit of treatment cannot be ruled out at one and six months. Pooled analyses were not possible for other treatments, either because too few trials had been performed, or because completed trials demonstrated significant heterogeneity. Many clinical trials in this area have been too small to give reliable results. Variations in the definition and reporting of postherpetic neuralgia create difficulties in combining data from different studies. Firm recommendations for clinical practice are not possible because existing evidence neither confirms nor refutes the hypothesis that treatment during the acute phase of herpes zoster reduces pain later. PMID- 7779478 TI - Patients in fundholding and non-fundholding practices. PMID- 7779477 TI - Readiness for lifestyle advice: self-assessments of coronary risk prior to screening in the British family heart study. Family Heart Study Group. AB - BACKGROUND: Where health professionals and patients hold similar views of a problem, health outcomes may be better. AIM: The aims of this paper were to document how attenders at primary care cardiovascular screening clinics perceived their risks of coronary heart disease prior to screening; the degree of similarity between perceived level of risk and an epidemiologically derived risk score; and the relative importance assigned to individual risk factors by subjects compared with those assigned by the risk score. METHOD: These issues were investigated in 3725 middle aged men and women who accepted an invitation to attend health screening as part of the British family heart study. RESULTS: Overall, there was a tendency for subjects to be optimistic (37%) rather than pessimistic (21%) when judging their risk of coronary heart disease. Nevertheless, there were strong significant associations between perceived risk and the levels of individual risk factors, particularly personal and family medical history and body mass index. There was also a strong association with the overall risk score though a large minority (31%) held views of their risk of coronary heart disease that were quite different from those based upon the epidemiologically derived index of risk. Respondents accorded greater importance to smoking and parental death from coronary heart disease and less importance to cholesterol level and blood pressure than did the risk score. CONCLUSION: Possible explanations for the observed disagreement are over-optimism or the relative importance given to individual risk factors. The relationships between patients' perceptions of risk and the epidemiological indices likely to be espoused by health professionals are important in understanding the difficulties in communication that might arise in offering lifestyle advice after screening for cardiovascular risk. PMID- 7779479 TI - Surveys of GPs: methodological considerations. PMID- 7779480 TI - Leicester assessment package. PMID- 7779481 TI - Identifying the agenda in the consultation. PMID- 7779482 TI - Quality of minor surgery in general practice. PMID- 7779483 TI - Quality of minor surgery in general practice. PMID- 7779484 TI - Rural general practice. PMID- 7779485 TI - Paperless medical records--approval still awaited. PMID- 7779487 TI - Marfan's syndrome. PMID- 7779488 TI - Diagnosis and treatment of Helicobacter pylori infection in peptic ulcer disease. PMID- 7779486 TI - A family care approach for managing childhood asthma. AB - Asthma is the most common chronic illness in childhood, affecting more than 2 million children annually. Although families have always been responsible for daily maintenance care, management of acute exacerbations of asthma are now coming within the province of home care management. The comprehensive family care approach discussed in this article incorporates environmental therapy, psychoeducational therapy, and medication therapy in a three-pronged approach to promote successful management of asthma episodes while working to reduce their incidence. PMID- 7779490 TI - A College for Europe? PMID- 7779489 TI - Psoriasis. AB - Psoriasis is a chronic skin disease that has multiple presentations. Patients frequently present with concerns about the cosmetic changes that psoriasis produces. While psoriasis is rarely life-threatening, it can be very devastating to the affected individual. Consequently, the various presentations of psoriasis need to be known by the health care provider. In addition, other dermatological conditions that may be confused with psoriasis need to be identified as part of the differential diagnosis so that the appropriate treatment may be instituted and potential effects of psoriasis, both physical and emotional, may be minimized. PMID- 7779491 TI - Newcastle Dental School and Hospital celebrates its centenary. PMID- 7779492 TI - A misplaced molar. PMID- 7779493 TI - Inadequately trained dental surgeons. PMID- 7779494 TI - Broken dental forceps. PMID- 7779495 TI - HIV awareness. PMID- 7779496 TI - Traumatised teeth. PMID- 7779497 TI - Weekend orthodontists. PMID- 7779498 TI - April fool. PMID- 7779499 TI - April fool. PMID- 7779500 TI - Clinically essential. PMID- 7779501 TI - The status of the LDS qualification. PMID- 7779502 TI - Cross-infection control in general dental practice: dentists' behaviour compared with their knowledge and opinions. AB - This study aimed to establish how dentists' knowledge, opinion and behaviour about cross-infection control were related and how they were affected by their ages, gender and the sizes of the practices in which they worked. In 1990/91 all general dental practitioners in the North Western Health Region of England were asked to complete a questionnaire about cross-infection control; 917 (75%) did so. Responses from all single-handed and one dentist selected randomly from each group practice were analysed (n = 546). The score to measure behaviour was based on guidelines on cross-infection control issued by the British Dental Association and this was correlated with scores for knowledge and opinion. The more knowledgeable not only tended to hold favourable opinions about the guidelines but also to practise them. Younger dentists were more knowledgeable about cross infection control measures than older and more likely to wear gloves. Irrespective of age, all female dentists were more likely to wear gloves than their male colleagues. Single-handed dentists were less willing to treat carriers of HIV and HBV. Although 65% thought that recommended control procedures are feasible, 43% considered them prohibitively expensive. PMID- 7779503 TI - The relationship between the index of orthodontic treatment need and consensus opinion of a panel of 74 dentists. AB - This study looked at the aesthetic and dental health components of the index of orthodontic treatment need in relation to peer assessment of dental health and aesthetic need (panel of 74 dentists). The dental health component had a Spearmans correlation coefficient of +0.64 and the aesthetic component +0.86 when compared with the mean subjective opinion of 74 dentists. It has been proposed to have three categories for both the dental health and aesthetic components in accordance with consensus opinion. The panel of 74 examiners were more likely to regard aesthetics as a greater need for treatment than dental health. PMID- 7779504 TI - Palatal root hemisections and subsequent tooth restoration: a simple procedure? AB - This article describes a simple procedure for palatal root hemisection in maxillary molars and their subsequent restoration. Hemisection has several advantages over resection at all stages and allows for simple prosthetic restoration, especially when treating the palatal root. PMID- 7779505 TI - Periodontology: a clinical approach. 6. Reconstructive periodontal treatment. PMID- 7779506 TI - The first triennium of the Commonwealth Dental Association. AB - Formed in 1991 to address the increasing prevalence of oral diseases and shortage of resources in many of the Commonwealth countries, the Commonwealth Dental Association (CDA) is celebrating its first triennium. Having achieved a successful and productive 3 years, the CDA is now looking to the next three with further goals in mind. PMID- 7779507 TI - Letters from California--the safety police. AB - I am sure many people imagine the United States of America as the land of the free, where people can do what they want unfettered by unnecessary rules, regulations and taxation. Unfortunately, the truth is very different and there are as many rules and regulations in the USA as almost anywhere else, and in some cases they are more complex since regulations come from both the federal government and the state government. Both may pass similar laws which differ in small degrees so there may be considerable areas of overlap but also considerable differences between the federal and state regulations. For dentists, a particular area of concern in recent years has been the agency known as OSHA, the Office of Safety and Health Administration. PMID- 7779508 TI - Seeing patients. AB - Seeing patients is something that we do most days. Indeed patients seeing us is something that happens most days too. Both situations are fine in the practice setting, but what happens outside? PMID- 7779509 TI - The molecular biology of nucleotide excision repair and double-strand break repair in eukaryotes. PMID- 7779510 TI - Uses for GAL4 expression in mammalian cells. PMID- 7779511 TI - The genetics of nuclear migration in fungi. PMID- 7779512 TI - Structure and function of the platelet-derived growth factor family and their receptors. PMID- 7779513 TI - Recombination between prokaryotic and eukaryotic DNA: integration of Agrobacterium tumefaciens T-DNA into the plant genome. PMID- 7779514 TI - Manipulating and mapping DNA with RecA-assisted restriction endonuclease (RARE) cleavage. PMID- 7779515 TI - Molecular studies on the virulence of Listeria monocytogenes. PMID- 7779516 TI - Role of molecular chaperones in the initiation of plasmid DNA replication. PMID- 7779518 TI - President's message: successful office practice management summit. PMID- 7779519 TI - Patient-focused care: been there, done that. PMID- 7779517 TI - Structure, function and engineering of Bacillus thuringiensis toxins. AB - Nature has provided potent insecticidal toxins as fermentation products of many Bacillus thuringiensis strains. Elucidation of structure-function relationships for this class of natural toxins is in its early stages. Both direct experimentation and application of theoretical structure-function principles emerging from the rapidly growing field of protein structure are accelerating understanding of these toxins. Coupled with the increasing demand for biologically sound pesticides, the benefits from engineering nature's toxins for improved performance set the stage for exciting, fast growth in discovery, characterization and commercialization of new active ingredients for biopesticides and transgenic plants. PMID- 7779520 TI - Review of ectodermal dysplasias for nurses. AB - The purpose of this continuing education feature is to introduce nurses to a group of disorders called ectodermal dysplasias. The ectodermal dysplasias are genetic disorders that affect individuals from all ethnic groups. Most of the features of ectodermal dysplasias can be evaluated easily and useful information can be given to affected individuals and their families about the disorder and readily available treatment. PMID- 7779521 TI - The role of home health nursing: a dermatologic case study. AB - The role of home health nursing is described in managing a postoperative wound infection. An 87-year-old woman underwent Mohs' cutaneous micrographic excision of an extensive basal cell carcinoma of the nose, with immediate reconstruction using a bilobed transposition flap. Her postoperative course was notable for an extensive wound infection characterized by cellulitis and local abscess formation. Inpatient admission was averted by using extensive home health nursing resources. PMID- 7779522 TI - What's your assessment? PMID- 7779523 TI - Dermatological management of Kaposi sarcoma. AB - Kaposi sarcoma (KS) is a chronic wound care problem for health care providers. Management of KS includes topical, intralesional, and systemic treatment modalities. The type of treatment used for KS depends on the classification of the disease which can be classical KS, African or endemic KS, iatrogenic immunosuppression KS, and epidemic or AIDS KS. PMID- 7779524 TI - Differential mechanism of retention of Cu-pyruvaldehyde-bis(N4 methylthiosemicarbazone) (Cu-PTSM) by brain and tumor: a novel radiopharmaceutical for positron emission tomography imaging. AB - The reductive retention of 62Cu-PTSM was comparatively studied in the brain and Ehrlich ascites tumor cells by electron spin resonance spectrometry and nonradioactive Cu-PTSM. In the brain, only the mitochondrial fraction showed the ability to reduce Cu-PTSM, and the other subcellular fractions did not. In contrast, the cytosolic fraction of Ehrlich ascites tumor cells was the specific site of Cu-PTSM reduction. It was therefore considered that the retention of Cu PTSM in the brain is closely related to mitochondrial reduction, most probably involving the mitochondrial electron transport system. PMID- 7779525 TI - Regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method. AB - By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO2) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear unplugged resting condition. Regional CBF was measured by the autoradiographic method after intravenous administration of H2(15)O. Regional OEF and rCMRO2 were measured by the single inhalation of 15O2. With MR T1-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO2 images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO2 values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO2 values among the cortical gyri. Regional OEF for the pontine nuclei (0.34 +/- 0.04), the midbrain (0.35 +/- 0.05), the parahippocampal gyri (0.35 +/- 0.04 for the right and 0.37 +/- 0.05 for the left), and the thalami (0.37 +/- 0.05 for the right and 0.36 +/- 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 +/- 0.04) (p < 0.05 or less). The global CBF and CMRO2 were consistent with those obtained by the Kety-Schmidt method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779526 TI - Qualitative and quantitative evaluation of renal parenchymal damage by 99mTc-DMSA planar and SPECT scintigraphy. AB - The initial 99mTc-DMSA studies carried out over a four year period in 229 patients with various heterogenic causes of lower urinary tract abnormalities were reviewed. Anatomical damage to the renal parenchyma was graded by means of planar and SPECT studies into a six group classification proposed by Monsour et al.: grade 0 (normal), I (equivocal), II (single defect), III (more than 2 defects), IV (contracted or small) and V (no visualization). Parenchymal uptake of 99mTc-DMSA was quantitated from planar images at 2 hours postinjection by a computer assisted gamma camera method. SPECT studies could enhance the pick-up rate for parenchymal uptake defects by a factor of 1.5 in comparison with planar imaging. The incidence of anatomical damage to the renal parenchyma increased with a high radiological grade for VUR, and renal uptake per injection dose of 99mTc-DMSA by the individual kidney significantly decreased in grades III and IV of the anatomical classification. These data revealed that 99mTc-DMSA planar is still useful for evaluating gross structural damage and for quantitative evaluation of the kidney with computer assistance. SPECT scintigraphy is more effective in disclosing anatomical damage to the renal parenchyma than planar, although it needs further discussion as to whether SPECT may increase sensitivity with minimal or no adverse affect on specificity. PMID- 7779527 TI - Postgastrectomy osteomalacia with pseudofractures assessed by repeated bone scintigraphy. AB - A patient with osteomalacia secondary to vitamin D deficiency after gastrectomy for gastric cancer is presented. Initial bone scintigrams showed both asymmetric and symmetric focal areas of intense uptake due to pseudofractures reminiscent of bone metastases. Radiographs only confirmed the presence of pseudofractures at some, but not all, of the abnormal sites demonstrated by bone scintigraphy. At first, metastatic bone disease was suspected. However, the appearance of repeated bone scintigram was normalized after treatment with vitamin D. A diagnosis of osteomalacia was established. The present case serves to illustrate that symmetric focal lesions are important features of pseudofractures secondary to osteomalacia, and comparison with radiographs and repeated bone scintigraphy are necessary in distinguishing between bone metastases and pseudofractures. PMID- 7779528 TI - Indium-111 antimyosin monoclonal antibody Fab imaging in patients with cardiomyopathy. AB - Six patients with cardiomyopathy were imaged following intravenous injection of an indium-111 labeled monoclonal antibody directed against the heavy chain of cardiac myosin. Two patients had hypertrophic non-obstructive cardiomyopathy (HNCM), two patients had dilated cardiomyopathy (DCM), and two patients had specific heart muscle disease. One of 2 patients with HNCM and one of 2 patients with DCM had a positive antimyosin scan. The 2 patients with specific heart muscle disease manifested persistent blood pool activity of the antibody, thereby precluding interpretation of the images. The present report demonstrates that antimyosin antibody imaging may provide evidence of myocardial injury, or necrosis in some patients with cardiomyopathy. PMID- 7779529 TI - A case of an intra-atrial tumor thrombus from hepatocellular carcinoma (HCC), first indicated by 67Ga-citrate scintigraphy. AB - We encountered a very rare case of an intra-atrial tumor thrombus from hepatocellular carcinoma (HCC). Conventional XCT and US gave evidence of HCC. In nuclear medicine studies performed incidentally, the first study with 99mTc phytate liver scintigraphy showed 2 SOLs and evidence of chronic liver disease, and the second study with 67Ga-citrate scintigraphy demonstrated 2 hot lesions within the liver parenchyma, and also another unexpected hot area just above the left lobe of the liver, seemingly beyond the diaphragm. When echocardiography was performed, in addition to ECG, because the patient began to complain of dyspnea, an oblong mass lesion was detected within the right atrium. Reexamination with XCT and angiography clearly proved the existence of an intraatrial tumor thrombus. These results indicate the need for routine examination by echocardiography for HCC patients complaining of dyspnea. PMID- 7779530 TI - Luxury perfusion phenomenon in acute herpes simplex virus encephalitis. AB - In a patient with acute herpes simplex virus (HSV) encephalitis, positron emission tomography (PET) demonstrated increased cerebral blood flow in the affected temporal lobe accompanied by reduction in the cerebral oxygen extraction fraction and the cerebral metabolic rate of oxygen, i.e., luxury perfusion. Follow-up PET studies showed reduction in cerebral perfusion until it was more closely coupled with oxygen metabolism after the resolution of the acute inflammation. These findings support previous single photon emission computed tomographic data and provide a pathophysiological background for the occurrence of hyperperfusion in HSV encephalitis. This is an interesting example of the luxury perfusion phenomenon occurring in a disease other than cerebral ischemia. PMID- 7779531 TI - Canine SPECT studies for cerebral amino acid transport by means of 123I-3-iodo alpha-methyl-L-tyrosine and preliminary kinetic analysis. AB - We have already reported that 123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) is superior as a single-photon emitter labeled radiopharmaceutical reflecting cerebral amino acid transport. In this study, we investigated the distribution of 123I-L-AMT in the canine head by means of SPECT and kinetically analyzed the data in the brain. As a result, clear SPECT images of the canine brain were obtained. Kinetic analysis with a 2-compartment model, including or expressing membrane transport of the amino acid, was performed with time-activity curves in the arterial blood and in the cerebral region. The results of the analysis coincided closely with the experimental data and the relevance of the model was strongly suggested. Therefore 123I-L-AMT is considered to be useful as a single photon radiopharmaceutical which enables us to measure the cerebral amino acid transport rate. PMID- 7779532 TI - Synthesis and preliminary evaluation of [1-11C]hexanoate as a PET tracer of fatty acid metabolism. AB - The potential of [1-11C]hexanoate (11C-HA) as a radiopharmaceutical assessing fatty acid metabolism of the myocardium and brain tissues by PET studies was evaluated. 11C-HA was synthesized by the Grignard reaction of pentylmagnesium bromide and 11CO2. 11C-HA, [1-14C]acetate and [3H]deoxyglucose were simultaneously injected i.v. into mice, and the tissue distribution of the three radionuclides was measured. In the heart, high uptake and rapid clearance of 11C and 14C was found. The brain uptake of 11C was twice as high as that of 14C, and both 11C and 14C decreased slowly compared to the heart. The level of 3H increased with time in both the heart and brain. In fasting conditions, the uptake of 11C by the heart was enhanced and the level of 3H decreased with time. The brain uptake of 11C and 3H was also enhanced. The fasting conditions did not affect the distribution of 14C. The radiation absorbed dose of 11C-HA was also estimated. PMID- 7779533 TI - Concentration and distribution of tumor associated antigens TAG-72 and CEA in stomach cancer. AB - We measured the concentration and distribution of tumor associated antigens, TAG 72 and CEA, in stomach cancer by in vitro quantitative autoradiography (IV-QAR). Frozen sections of 33 specimens were incubated with varying concentrations of 125I-labeled CEA-79.1 and B72.3 antibodies specific for carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72), respectively. Computer analysis of specific antibody binding gave maximal binding values which were equal to the concentrations of the antigen or epitope. TAG-72 was detected in 25 specimens, at a concentration ranging from 8.4 to 562.9 pmol/g. CEA was detected in 32 of the 33 specimens and its concentration ranged from 8.8 to 525.3 pmol/g. The distribution of TAG-72 by IV-QAR coincided with that of the tumor cells in 41.4% of the pathologic lesions. The distribution of CEA coincided with the tumor cells in 80.5% of pathologic lesions, nearly twice the TAG-72. The concentration of TAG-72 was significantly higher in mucinous adenocarcinoma and mucin containing adenocarcinomas than other types of adenocarcinomas. There was no significant difference in the concentration of CEA among the pathologic types of stomach cancer. In summary, stomach cancer exhibited wide variations in TAG-72 and CEA expression. CEA expression was more frequent and homogeneous than TAG-72. PMID- 7779534 TI - Trace Elements and Free Radicals in Oxidative Diseases. Proceedings of the 4th International Congress on Trace Elements in Medicine and Biology. Chamonix, France, April 5-9, 1993. PMID- 7779535 TI - Antioxidant status and lipid peroxidation in athymic mice xenografted with two types of human tumors. AB - Antioxidants and reactive oxygen species are considered to play an important role in experimental in vivo carcinogenesis studies. We attempted in this study to evaluate the repercussions on the antioxidant and lipid peroxide status of the growth of human malignant tumors xenografted into athymic mice. We selected three tumor models: two urothelial carcinomas (bladder tumors stage 3) and one brain tumor (glioblastoma stage 4). All these tumors exhibited a fast growth pattern when xenografted into athymic mice. Tumoral tissue was implanted subcutaneously. After growth establishment each tumor size was measured at regular intervals: every 2 d for bladder tumor and twice a week for glioblastoma. The period of observation was 3 wk for bladder tumors and 5 wk for glioblastoma. At the end of the observation period, all mice were sacrificed; tumoral tissue was taken and blood collected. Superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px), zinc (Zn), selenium (Se), and thiobarbituric acid reactive substances (TBARS) were measured in blood. TBARS alone were measured into tumoral tissue. A modification of the antioxidant blood status was observed in mice xenografted with bladder tumors with decrease in Se status and GSH-Px activities, and increase in TBARS. Such an effect was absent in mice xenografted with glioblastoma. It would appear that an oxygen-mediated stress exists in the animal bearing an implanted tumor compared with the control group, and that tumoral tissue itself is able to induce an oxidative stress into its host. All this leads to a disturbance of the antioxidant defense system. PMID- 7779536 TI - Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation. AB - Adriamycin (25 microM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron. PMID- 7779537 TI - Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy, including adriamycin. A preliminary study. AB - Adriamycin is a potent chemotherapeutic agent used in the treatment of human neoplastic diseases. A major side effect limiting the use of this drug is its toxic effect on the heart. Several hypotheses have been proposed to explain the cardiotoxicity of Adriamycin. However, the most plausible hypothesis seems to be the reduction of Adriamycin and free radical production, which induces lipid peroxidation and oxidative damages in the heart. We have thus undertaken this preliminary study to investigate Adriamycin-induced lipid peroxidation by the measurement of plasma thiobarbituric acid reactant materials and antioxidant systems, namely glutathione content, glutathione peroxidase activity, and vitamin and trace element status, in patients with cancer before and after chemotherapy, including Adriamycin. The concentration of thiobarbituric acid reactant materials in plasma of patients with cancer was higher than in controls and was further increased after chemotherapy. Blood glutathione and plasma glutathione peroxidase activity, as well as plasma zinc and selenium in patients with cancer, were decreased, but not further modified by chemotherapy. However, only zinc and selenium levels reached a significant level. In contrast, plasma vitamin E and beta-carotene levels were not significantly increased in patients with cancer. Finally, plasma vitamin A and copper levels were not modified either in patients with cancer or by chemotherapy. PMID- 7779539 TI - Relationship of trace element, immunological markers, and HIV1 infection progression. AB - Trace elements (selenium, zinc, copper), beta 2 microglobulin levels, CD4, and CD8 cell counts have been determined in 80 HIV1 seropositive patients. The study group consisted of 19 females and 61 males with age mean of 35 +/- 10 yr, at stage IV of infection (CDC--Atlanta classification) and treated by AZT. No severe renal or liver diseases or hypoalbuminemia were observed in this group. Se values were significantly lower than in normal adults, 48.3 +/- 17 micrograms/L vs 71 +/ 12 micrograms/L; Zn was moderately diminished, 1 +/- 0.2 mg/L vs 1.2 +/- 0.2 mg/L, whereas copper values were in the normal range, 1.2 +/- 0.3 mg/L vs 1.1 +/- 0.5 mg/L. Se or Zn deficiency was found in 60 and 30 subjects, respectively. Blood Se and Zn decreases were associated in 23 patients. Moreover, all patients showed higher beta 2 microglobulin values than the upper normal limit of 2.4 mg/L. Negative correlations were found between Zn and beta 2 microglobulin (p < 0.005) and between Se and beta 2 microglobulin (p < 0.05). Moreover, there was a positive correlation between Se and Zn values (p < 0.05). Nineteen subjects died 1 yr later (group I), and 61 remained alive (group II). With respect to the clinical evolution, a significant difference between both groups was found in Se and beta 2 microglobulin levels as well as in CD4 cell counts. The correlations previously observed persisted in group II, whereas no correlation was noted in group I. In addition, the patients of group one had significantly lower Se values, which were below 30 micrograms/L in 10 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779538 TI - Lipoperoxides as an index of free radical activity in bone marrow transplant recipients. Preliminary observations. AB - It has been previously demonstrated that the conditioning therapy given to bone marrow transplant (BMT) recipients creates a high oxidant stress, resulting in a measured reduction in antioxidants, such as glutathione peroxidase (GSH-Px), vitamin E, and cell peroxide fragilities. As part of a current intervention trial of antioxidant therapy in BMT recipients, plasma thiobarbituric acid reactive substances (TBARS) were measured to assess peroxidation and free radical activity. Measurements were performed before and after conditioning therapy, and then at weekly intervals for a period of 6 wk after transplantation in 20 patients (10 controls and 10 antioxidant therapy [AOT] recipients). The TBARS results were compared with concurrent measurements of more specific elements of the antioxidant pathways, such as red blood cell glutathione peroxidase (RBC-GSH Px), plasma vitamin C, and serum vitamin E. In all cases, TBARS concentration was significantly increased after conditioning compared with baseline levels (p < 0.001), an increase that correlated inversely with RBC-GSH-Px (r = -0.81; p < 0.01). The TBARS concentration fell gradually after conditioning in all patients. The fall in the AOT group was more rapid than in the control group, and it paralleled the gradual return toward normal levels of the other antioxidants. The change in TBARS concentration occurred faster than changes in other indices, suggesting that TBARS might be a better index of overall free radical activity. Although the patient numbers are small, there is some evidence to suggest that MDA may act as a prognostic marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779540 TI - Evaluation of zinc content in children's hair. AB - The zinc content in the hair of 654 children living in various rural and industrial areas in southern Poland was assayed by means of the atomic absorption spectrometry, following the dry digestion procedure. The hair of girls exhibited statistically significant higher level of Zn than the boys' hair, although in the site of extremal Zn contamination, the inverse relation was found. PMID- 7779541 TI - Lipid peroxidation assessed by serum thiobarbituric acid reactive substances in healthy subjects and in patients with pathologies known to affect trace element status. AB - Serum thiobarbituric acid reactive substances (TBARS), Zn, Cu, and Se concentrations were determined in 47 healthy adults and in patients with diseases, such as renal insufficiency, insulin-dependent diabetes mellitus, chronic pancreatitis, liver cirrhosis, or cancer, in order to clarify the relationship between this indicator of lipid peroxidation and antioxidative trace element status. TBARS levels were higher than control values in all pathological cases, except in cancer patients. Cu levels in patients highly correlated with ferroxidase ceruloplasmin activity (r = 0.86), but were only statistically different from controls in diabetics. Zn levels were lower than normal in dialysis, liver cirrhosis, and cancer patients. Se levels were significantly decreased in all pathological cases. Half of the subjects with liver cirrhosis or renal insufficiency and 3/4 of chronic pancreatitis or cancer patients had an active inflammatory process. Despite intense modifications in determined indicators, no clear correlation could be demonstrated between the different parameters. Basic antioxidative trace element status and inflammation are therefore not major determinants of TBARS levels in normal and in pathological conditions, despite of the frequent association of low serum Zn and mainly low serum Se with high TBARS levels. PMID- 7779543 TI - The relevance of malondialdehyde as a biochemical index of lipid peroxidation of postischemic tissues in the rat and human beings. AB - By using a recently developed ion-pairing high-performance liquid chromatographic method for the direct determination of malondialdehyde (MDA) and several other acid-soluble low-mol-wt compounds (ascorbate, oxypurines, nucleosides, nicotinic coenzymes, high-energy phosphates), the variations of tissue and plasma MDA as a function of ischemia and reperfusion were determined in the rat (isolated Langendorff-perfused hearts and short-term incomplete cerebral ischemia) and in human beings (patients suffering from acute myocardial infarction subjected to fibrinolysis). In the rat, the data obtained indicate that, contrary to what had been previously reported in literature, MDA is not present either in control heart or in control brain. Oxygen deprivation induces the production of a low, but detectable amount of MDA in both heart and brain, whereas reperfusion causes a marked increase of MDA in both tissues. In human beings, plasma MDA was deeply affected only in patients suffering from acute myocardial infarction with successful thrombolysis, thus indicating the occurrence of oxygen radical mediated tissue injury also in humans. On the whole, these results suggest that MDA is a valid biochemical marker of lipid peroxidation of postischemic tissues, which however needs a reliable analytical technique for its determination. PMID- 7779542 TI - Selenium, oxygen-derived free radicals, and ischemia-reperfusion injury. An experimental study in the rat. AB - Circulatory shock and its treatment have been compared to a whole-body ischemia and reperfusion with activation of oxygen-derived free radicals. A pilot study had suggested a selenium redistribution in this context. To verify this hypothesis, an experimental study was designed. Temporary occlusion of the superior mesenteric artery was performed in 18 male adult Wistar rats using clamping for 0, 10, and 20 min. Hemodynamic and biochemical data were assessed before clamping and 20 min after release of the mesenteric blood flow. After release, mean arterial pressure decreased, plasma lactate increased, and erythrocyte glutathione peroxidase decreased. Plasma and erythrocyte selenium did not change; however, a slight decrease in plasma selenium was observed when related to hematocrit (to take into account the fluid balance). Erythrocyte reduced glutathione did not change. In contrast, liver and kidney selenium increased, whereas reduced glutathione decreased in kidney, but not in liver after 20 min of clamping as compared to the sham-operated group. These results suggest that, after temporary intestinal ischemia, the changes in selenium and reduced glutathione observed in blood and tissues, like liver or kidney, could be related to a redistribution pattern in selenium metabolism during shock injury. PMID- 7779544 TI - Immunological approach to investigating membrane cell damages induced by lipoperoxidative stress. Application to far UV-irradiated erythrocytes. AB - Oxygen-reactive species are being described as agents responsible for cell degeneration mechanisms resulting from membrane, enzyme, and nuclear alterations. Lipid peroxidation on its own is considered to be one of the consequences of the free radicals attack, and among the different reactive aldehydes that can be formed from the decomposition of lipid peroxides, the most extensively assayed have been malondialdehyde (MDA). However, the different techniques currently used for MDA assay (HPLC, GLC) are barely sensitive enough to follow its production at the cellular level. In order to develop an immunofluorescent technique able to detect cellular damages provoked by lipoperoxidation, polyclonal antibodies against lysozyme modified by MDA treatment have been raised in rabbits. We show that this immunserum recognizes specifically all the MDA-treated proteins tested, but not the intact proteins or the proteins treated by other aldehydes. Moreover, we demonstrate using an ELISA technique that the amount of immunoreactive proteins in MDA-treated membrane erythrocytes is proportional to the concentration of MDA applied, suggesting that this assay may represent a quantitative method of determination of lipoperoxidative alterations. In addition, when coupled to an indirect fluorophore antibody (FITC), the immunserum allows a precise location of these modified proteins within the membranes of erythrocytes in which lipid peroxidation was initiated by far UV irradiation. In summary, the interest of this work is to provide an immunological probe that can precociously detect membrane damages induced by MDA, regardless of the cell type and pro-oxidant (physiological or pathological) conditions. PMID- 7779546 TI - Increase in cellular pool of low-molecular-weight iron during ethanol metabolism in rat hepatocyte cultures. Relationship with lipid peroxidation. AB - Ethanol-induced lipid peroxidation was studied in primary rat hepatocyte cultures supplemented with ethanol at the concentration of 50 mM. Lipid peroxidation was assessed by two indices: (1) conjugated dienes by second-derivative UV spectroscopy in lipid extract of hepatocytes (intracellular content), and (2) free malondialdehyde (MDA) by HPLC-UV detection and quantitation for the incubation medium (extracellular content). In cultures supplemented with ethanol, free MDA increased significantly in culture media, whereas no elevation of conjugated diene level was observed in the corresponding hepatocytes. The cellular pool of low-mol-wt (LMW) iron was also evaluated in the hepatocytes using an electron spin resonance procedure. An early increase of intracellular LMW iron (< or = 1 hr) was observed in ethanol-supplemented cultures; it was inhibited by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, whereas alpha-tocopherol, which prevented lipid peroxidation, did not inhibit the increase of LMW iron. Therefore, the LMW iron elevation was the result of ethanol metabolism and was not secondarily induced by lipid hydroperoxides. Thus, ethanol caused lipid peroxidation in rat hepatocytes as shown by the increase of free MDA, although no conjugated diene elevation was detected. During ethanol metabolism, an increase in cellular LMW iron was observed that could enhance conjugated diene degradation. PMID- 7779545 TI - Time-course of changes in plasma levels of trace elements after thrombolysis during the acute phase of myocardial infarction in humans. AB - It has been suggested that the injury induced by reperfusion of the ischemic myocardium could result, in part, from the cytotoxic effects of oxygen free radicals. Since various trace elements are involved in several of the reactions leading to free radical production, we have measured plasma levels of copper, zinc, selenium, and iron: 1. In 18 patients (mean age 60 yr old) subjected to thrombolytic therapy within 6 h after the onset of a myocardial infarction (G1); 2. In 16 patients with coronary artery disease, but without a history of a previous myocardial infarction (MI) (mean age 50 yr old, G2); and 3. In 50 healthy volunteers divided into two subgroups according to age (mean age 33 yr old, G3 and 55 yr old, G4). Plasma myosin levels were used to estimate quantitatively the extent of the infarcted mass. Plasma trace element levels were measured in blood samples following centrifugation and storage at -80 degrees C. The main results were as followed: In G1 patients who have been subjected to thrombolysis, an important release of myosin was measured in plasma, with a peak at D6 (1678 vs 95 microU/L at H0). In those G1 patients after MI: 1. A significant increase in plasma copper levels was observed from day 4 to day 10 postinfarction (x1.15 in reference to the baseline data at H0); 2. A decrease in plasma zinc levels was observed and was maximum 12 h after the onset of the thrombolytic treatment; 3. A decrease in selenium concentration was observed in G1, as well as in G2 patients, compared to the control groups (80% of G3 and G4 values); and 4. A significant decrease in plasma iron levels was observed in G1 (67.8% of G3 and G4 control values) and was significant from H0 to day 7 (p < 0.01). In conclusion, this study underlined the time-course evolution of plasma trace element levels in the followup of patients who have been subjected to thrombolysis following a MI and the potential prognostic implication of such variations. PMID- 7779547 TI - Zinc, iron, and peroxidation in liver tissue. Cumulative effects of alcohol consumption and virus-mediated damage--a preliminary report. AB - In an attempt to elucidate further the mechanisms involved in alcohol-mediated liver damage and the correlation between alcohol and viruses in chronic liver lesions, we determined the levels of liver glutathione (GSH), thiobarbituric acid reactive substances (TBARS), iron (Fe), and zinc (Zn) in 31 patients with chronic viral hepatitis (CAH), 6 with alcohol-related chronic hepatitis (CALD), 6 with alcoholic cirrhosis (AC), 8 with primary biliary cirrhosis (PBC), and 10 healthy controls (C). Liver GSH was significantly lower in CALD and AC patients (p < 0.005). TBARS levels were significantly higher in CAH, CALD, and PBC patients (p < 0.001, < 0.02, and < 0.001, respectively). In CAH patients, alcohol consumption correlated inversely with GSH and directly with TBARS (p < 0.05). Patients with both CAH and alcohol abuse had a further reduction in liver GSH levels (p < 0.005). Tissue levels of Fe were significantly increased in CALD and AC patients with respect to controls and CAH patients, whereas no significant difference was observed in Zn. These data confirm that patients with chronic ethanol exposure reveal a depletion in liver GSH content clearly correlated with an increase in lipid peroxidation and Fe liver storage. On the other hand, these findings appear to suggest no significant change in Zn levels in chronic hepatitis. PMID- 7779549 TI - Trace element status and inflammation parameters during chronic indomethacin treatment in adjuvant arthritic rats. AB - Oral indomethacin administration (2 mg/kg/d) was investigated in rats with adjuvant arthritis up to a period of 5 wk. Baseline low serum zinc levels in arthritic rats increased rapidly from the first week of indomethacin treatment (started 1 or 2 wk after disease induction), whereas baseline high serum copper decreased after 1-2 wk. After 3-4 wk of treatment, serum zinc levels returned to control values, but serum copper was somewhat higher in arthritic animals having received indomethacin 2 wk after disease induction than in controls. Clinical indices of inflammation simultaneously improved to reach control values at the end of the trial. Biological indicators of inflammation also improved, but did not reach control levels. Serum zinc correlated negatively with plasma fibrinogen (r = -0.69, p < 0.0005) and serum copper correlated positively with serum ceruloplasmin (r = 0.92, p < 0.0005) both in indomethacin-treated and untreated arthritic rats. Contrary to long-term glucocorticoid administration that was previously reported to maintain or aggravate hypozincemia, indomethacin treatment normalized perturbed zinc and copper status in arthritic animals. PMID- 7779550 TI - The susceptibility to stress-induced gastric injury of rats exposed to cadmium. AB - In this experimental study, the effect of cadmium on cold and restraint stress induced gastric lesions has been studied. Rats received 15 micrograms/mL cadmium containing water for 30 d, and at the end of this period, they were subjected to cold and restraint stress. Cadmium accumulation in gastric mucosa was associated with increased mucosal lesions, as well as decreased mucin and PGE2 levels in rats exposed to cadmium. Stress-induced mucosal injury was more pronounced, and the hemoglobin leakage into gastric lumen owing to breakdown in the barrier was 17.30 +/- 3.45 micrograms/mL in control and 35.71 +/- 6.18 micrograms/mL in treated rats. Our data suggest that high cadmium intake facilitates the occurrence of stress-induced mucosal lesions by diminishing the mucin content and PGE2 generation in gastric mucosa. PMID- 7779548 TI - Low selenium status in alcoholic cirrhosis is correlated with aminopyrine breath test. Preliminary effects of selenium supplementation. AB - The relationship among impaired selenium status, lipid peroxidation, and liver function was examined in 19 hospitalized patients with severe alcoholic cirrhosis. Plasma selenium was found to be significantly lower (mean +/- SD: 54 +/- 13 micrograms/L) than in healthy controls (83 +/- 11 micrograms/L) and plasma malondialdehyde, assessed as thiobarbituric acid reactants, which reflects lipid peroxidation, was increased (2.0 +/- 1.2 mumol/L vs < 1.2 mumol/L in controls). The mean 14C aminopyrine breath test, an indicator of liver function, was lower than normal (2.7 +/- 1.9 vs 6.3 +/- 0.9% in controls) and found to be significantly correlated with plasma selenium (r = 0.59, p < 0.05). A prospective, randomized selenium supplementation trial was conducted in a group of 16 patients who received either daily 100 micrograms selenium as enriched yeast during 4 mo or a placebo. Among the 10 patients who completed the study, plasma selenium significantly increased in the supplemented group (n = 4; before: 58 +/- 10 micrograms/L, and after 101 +/- 12 micrograms/L, p < 0.01) contrary to the placebo group (n = 6, before: 47 +/- 10 micrograms/L, after: 57 +/- 9 micrograms/L, n.s.). 14C aminopyrine breath test improved in three out of four selenium-supplemented patients and in three out of six placebo patients, but the small number of patients did not allow statistical evaluation. These results demonstrate that low selenium status in alcoholic cirrhosis is correlated to liver function and could be improved by supplementation. PMID- 7779551 TI - Modification of the blood-brain barrier through chronic intoxication by aluminum glutamate. Possible role in the etiology of Alzheimer's disease. AB - The authors have used an experimental rat model of chronic aluminum (Al) intoxication to reproduce pathological signs analogous to those observed in humans for Alzheimer's disease or dialysis encephalopathy. Preliminary chronic intoxication was achieved during 5 wk by daily subcutaneous injection of a suspension of glutamate and Al prior to intravenous (i.v.) administration of sodium L-glutamate and Al chloride. A significant increase in Al content was observed in different areas of the brain, such as the hippocampus, the occipito parietal cortex, the cerebellum, and the striatum. Moreover, half of the animals subcutaneously treated with Al glutamate had neurological disturbances, such as trembling, equilibrium difficulties, and convulsions leading to death about 1 h after i.v. administration. A significant increase in glutamic acid at the level of the occipito-parietal cortex was found in comparison with controls, which received only sodium L-glutamate or saline solution. These results show that the Al-L-glutamate complex may well induce a modification of the blood-brain barrier. PMID- 7779552 TI - Serum aluminum levels in Alzheimer's disease and other senile dementias. AB - The exact cause of Alzheimer's disease and the part played in it by aluminum is still speculative. We have studied serum aluminum in 356 healthy people, and we have observed that serum aluminum concentration is increased in aging people in relation to age. We suggest that this could be associated with an enhanced gastric permeability or by an increase in metal accumulation proportional to age. We have measured serum aluminum levels in patients with probable Alzheimer's disease, patients with other senile dementias, and age-matched group. Patients with probable Alzheimer's disease have statistically significant higher serum aluminum levels than patients with other types of senile dementias (alcoholic, vascular, multi-infart) and an age-matched control group. When we compare serum aluminum of patients with senile dementias from other causes with the age-matched control group, we do not find significant differences. PMID- 7779553 TI - Incomplete cerebral ischemia in the rat provokes increase of tissue and plasma malondialdehyde. AB - Short-term incomplete cerebral ischemia was induced in the rat by bilaterally clamping for 5 min the common carotid arteries; subsequent reperfusion of 10 min was obtained by removing carotid occlusion. At the end of ischemia or reperfusion, animals were sacrificed by decapitation. A control group was represented by sham-operated rats. Peripheral venous blood samples were withdrawn from the femoral vein from rats subjected to cerebral reperfusion 5 min before ischemia, at the end of ischemia, and 10 min after reperfusion. A highly sensitive HPLC method for the direct determination of malondialdehyde, oxypurines, and nucleosides was used on 200 microL of brain tissue and plasma extracts. Incomplete cerebral ischemia induced the appearance of a significant amount of tissue malondialdehyde (undetectable in control animals) and a decrease of ascorbic acid. A further 6.6-fold increase of malondialdehyde and a 18.5% decrease of ascorbic acid occurred after 10 min of reperfusion. Plasma malondialdehyde, which was present in minimal amount before ischemia, significantly increased after 5 min of ischemia, being strikingly augmented after 10 min of reperfusion. A similar trend was observed for oxypurines and nucleosides. From these data, it can be affirmed that tissue concentrations of malondialdehyde and ascorbic acid, and plasma levels of malondialdehyde, oxypurines, and nucleotides, reflect both the oxygen radical-mediated tissue injury and the depression of energy metabolism, thus representing early biochemical markers of short-term incomplete brain ischemia and reperfusion in the rat. PMID- 7779554 TI - In vitro influence of zinc and magnesium on the deformability of red blood cells artificially hardened by heating. AB - Trace elements have been shown to improve red blood cell (RBC) deformability: zinc in sickle cell disease and magnesium in an in vitro model of chemically rigidified erythrocytes. In this study, we investigated the effect and the influence of incubation time of zinc or magnesium on an in vitro model of rigidified RBCs by heating. Erythrocyte rigidity was determined by viscosimetry at high shear rate by a falling ball viscosimeter MT 90. In the first part of the study, six normal volunteers participated. Viscosimetry was performed on native blood before and after heating the sample for 10 min at 50 degrees C. Therefore, increasing concentrations of zinc gluconate (final concentration: 0.5-4 g/L) or isotonic NaCl as control medium were added to the sample. Heating induced a twofold increase in all indices of RBC rigidity (p < 0.05). At all these concentrations of zinc, a highly significant, dose-related fluidifying effect was observed (40-70%): this effect was immediately obtained and did not change over 60 min. Even at the highest concentration, recovery was not complete. In the second part of the study, we studied magnesium's effects on blood. In a first protocol, whole blood was rigidified by heating at 56 degrees C for 10 min, and the correcting effect of 5 min of incubation at 37 degrees C of RBCs in 150 mmol/L NaCl, MgSO4, magnesium acetate, and magnesium gluconate was investigated. In a second protocol, the same incubation with NaCl and magnesium salts was made on blood that had not been previously heated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779555 TI - The effect of age and selenium on some biochemical parameters in rat liver. AB - Two age groups, 3 and 15 mo, were used to investigate whether age-associated changes in some parameters related to lipid peroxidation occur in the liver of male Wistar rats and to observe possible effects of dietary selenium supplementation (0.25 and 0.50 ppm) for 12 mo on the same parameters. At these experimental conditions, the most important observation was that peroxidation did not change by aging, at least until 15 mo of age. In addition, the activity of Se dependent glutathione peroxidase (GSH-Px, EC 1.11.1.9) was higher in the liver of the older animals. It is suggested that the enzyme could have a role in the unchanged hepatic peroxidation observed in aged male rats. On the other hand, an effect of dietary selenium supplementation on those parameters was not observed, probably because the selenium levels were still at an adequate plateau. PMID- 7779556 TI - Free radicals production and estimation of oxidative stress related to gamma irradiation. AB - The effectiveness of chemiluminescence (ChL) in vitro to measure free radicals generated as a result of metabolic disorganization caused by radiation sickness is evaluated. The results are correlated with those obtained by measuring superoxide dismutase (SOD) activity and lipid peroxide as levels of thiobarbituric acid reacting substances (TBARS). To this aim, livers from irradiated Wistar rats were removed immediately (day 0) after irradiation and also 7 and 14 d later. ChL results, expressed in arbitrary units (AU)/min/mg protein, were analyzed for irradiated samples and controls, for different doses at different times. Increased levels of ChL emission were observed not only on day 0, but also on days 7 and 14. On the other hand, SOD activity showed a decrease on the 7th d, and significantly higher lipid peroxide levels were observed in the assays performed on the 14th d, at all exposure doses. The correlation between temporal changes in the SOD activity, ChL emission, and higher TBARS levels a week later were evident from the data. These results indicate that the ChL technique proved to be useful in combination with other techniques currently used for evaluating radiation oxidative injury. PMID- 7779557 TI - Serum zinc in highly trained adolescent gymnasts. AB - Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12-15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599 +/- 0.026 mg/L) when compared to matched control sedentary children (n = 118 mean 0.81 +/- 0.014 p < 0.001). Girls had lower zinc than boys (0.557 +/- 0.023 vs 0.651 +/- 0.044 p < 0.001). Zinc was correlated to isometric adductor strength (r = 0.468 p < 0.05). Children with serum zinc < 0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326 +/- 0.264 vs 2.699 +/- 0.12 p < 0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance. PMID- 7779558 TI - Muscle GSH-Px activity after prolonged exercise, training, and selenium supplementation. AB - A double-blind study of the effects of supplementing with selenium vs. placebo on the physiological responses to acute and chronic exercise was conducted in 24 healthy, nonsmoking males, mean age 22.9 +/- 2.1 yr, randomly divided into two groups of 12 (Pla/Sel). After a controlled period in the absence of training, all subjects were put on an individualized endurance training program with the same rules of progression and overload (3 sessions/wk x 10 wk). Supplementation, either real (240 micrograms of organic selenium/d in Sel group) or imaginary (Pla group) was administered during the same period. In each of the conditions Pre- and Post- (training +/- sel supplementation), muscle, plasma, and systemic parameters were determined before (BF) and after (AF) acute exercise, involving the repetition of muscle work cycles separated by 5-min recovery periods, combining 20 min at 65% and a maximal duration of 100% VO2 max of running on a treadmill, leading the subjects to exhaustion between 2 h 40 min and 3 h 30 min. Changes in parameters as a function of three independent variables: 1. Acute exercise (E); 2. Chronic exercise (T); and 3. Selenium supplementing (S) were tested with ANOVA and the Student's t-test on paired series. Among the variables examined, muscle glutathione peroxidase (GPx) presented a remarkable behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779559 TI - Environmental effects of nationwide selenium fertilization in Finland. AB - To study the possible pollution of natural waters by selenium added to agricultural fertilizers, water selenium concentrations were determined in lakes and ground water pools during the year 1992, when the enrichment of fertilizers by selenium had continued for 8 yr. Water samples were preconcentrated by evaporating, and selenium concentrations were analyzed fluorometrically using the dye 2,3-diaminonaphthalene after wet digestion. In lake water samples from 13 lakes, no significant correlations were found between selenium and pH, chlorophyll A, total nitrogen, or phosphorus. Agriculturally affected and nonaffected lakes had no differences in their selenium concentrations. In the lakes that were surrounded by cultivated fields mean water selenium was 83.4 ng/L (range: 75.2-93.4 ng/L, n = 9). Correspondingly, in lakes situated in forests without agricultural surroundings, mean water selenium concentration was 76.5 ng/L (range: 51.2-110 ng/L, n = 3). Only one lake in the close vicinity of a coal power plant had a high water selenium concentration (mean 272 ng/L). In ground water samples, there was a big variation in selenium levels between different pools, the levels varying between 33 and 260 ng/L. This variation may partly be explained by different selenium concentrations of the bedrock and sediments. However, simultaneous increase of total nitrogen, phosphorus, and selenium levels in consecutive samples from some ground water pools indicates leaching of selenium from the fertilizers into the ground water in certain areas. PMID- 7779560 TI - A comparison of four assays detecting oxidizing species. Correlated reactivity of Fe(III)-quin2, but not Fe(III)-EDTA, with hydrogen peroxide. AB - Quin2, a fluorescent calcium probe, has a low affinity for calcium in comparison to its affinities for transition metal ions. Chelation of ferric ion with quin2 strongly enhanced the formation of oxidizing species in the presence of bolus H2O2 as detected with four assays, electron spin resonance with the spin-trap DMPO, the deoxyribose assay, the DMSO assay, and plasmid DNA strand breakage. In comparison, Fe(III)-EDTA reacted with bolus H2O2 only as detected with electron spin resonance and deoxyribose assay, but not as detected with the two latter assays. The addition of reductants, like ascorbate or superoxide generated by hypoxanthine/xanthine oxidase, to Fe(III)-EDTA in the presence of H2O2 produced plasmid DNA strand breakage and strong reactivity in both the DMSO and the deoxyribose assays. Our findings suggest that the main oxidizing species produced in Fenton-type reactions is hydroxyl radical. However, the reaction between Fe(III)-EDTA and bolus H2O2 appears to be exceptional and dominated by a nonhydroxyl radical species. PMID- 7779561 TI - In vitro anti- and pro-oxidative effects of natural polyphenols. AB - The anti- and pro-oxidative effects of phenolic compounds and antioxidants were studied in two different in vitro model systems utilizing ethyl linoleate and 2' deoxyguanosine (2'-dG) as oxidative substrates, and a Fenton reaction (H2O2, Fe2+) to initiate oxidation. Oxidation of the biomolecules in both model systems exhibited dose dependency. In the 2'-dG assay, oxidation was closely related to H2O2 generation, which occurred during autoxidation of the phenolics. Hydroxylating activity was greatly enhanced by Mn2+ and Cu2+, but not by Zn2+ or Co2+. Ethyl linoleate peroxidation was inhibited by low concentrations of catechol, quercitin, and instant coffee. However, peroxidation was promoted by high concentrations of the same compounds, probably by recycling of chelated inactive Fe3+ to the active Fe2+ state. PMID- 7779562 TI - Lack of correlation between TBARS production and PUFA degradation during incubation of membrane erythrocytes in an OH. (Fe2+/H2O2) generator system. AB - We investigated the effects of an OH. (Fe2+/H2O2) generator system on erythrocyte membrane, particularly the time-course of lipid peroxidation as estimated by measurement of conjugated dienes, thiobarbituric reactive substances (TBARS), lipofuscin-like pigments, and alpha-tocopherol. Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (20:4 omega 6) and docosahexenoic acid (22:6 omega 3), were also measured. Erythrocyte membranes were suspended in phosphate buffer containing Fe2+ (200 microM) and H2O2 (1.42 mM), and incubated in a shaking water bath at 37 degrees C. Initially, there was an increase in TBARS and lipofuscin-like pigments, two well-known end products of PUFA oxidative degradation, whereas PUFAs remained unchanged (incubation time: 1 h). After two or more hours of incubation, marked lipid peroxidation was noted, with the appearance of conjugated dienes and a decrease of PUFAs, indicating that lipid peroxidation had occurred after a lag phase during which TBARS were not produced from PUFAs. This suggests that another OH. target was involved. PMID- 7779563 TI - Pentoxifylline. A hydroxyl radical scavenger. AB - Pentoxifylline (PTX), a tri-substituted purine and xanthine derivative, has been used for several years to improve microcirculation because of its hemorheological properties. PTX has also antifibrotic and anti-inflammatory effects. We studied the reaction of PTX with the hydroxyl radical and superoxide anion. Hydroxyl radical was generated by a mixture of ascorbic acid, H2O2 and Fe(III)-EDTA. We evaluated the iron-dependent degradation of deoxyribose, mediated by hydroxyl radical, in the presence of different concentrations of PTX (from 0.05 to 3 mM), measuring the degradation products of deoxyribose that react with 2 thiobarbituric acid (TBA). The reaction of PTX with hydroxyl radical occurred with a rate constant of (1.1 +/- 0.2) x 10(10) M-1/s. These results support the properties of PTX as a hydroxyl radical scavenger. Some authors verified that PTX decreases the release of superoxide anion from activated neutrophils. We studied the effect of PTX as a scavenger of superoxide generated in vitro by a hypoxanthine-xanthine oxidase system. PTX was not a superoxide anion scavenger in this system. PMID- 7779565 TI - Induction of lipid peroxidation and alteration of glutathione redox status by endosulfan. AB - The oxidant stress-inducing effects of endosulfan, a chlorinated hydrocarbon insecticide of the cyclodiene group, have been examined following ig administration of single and repeated doses. A single dose of 30 mg/kg (approximately 30% LD50) endosulfan significantly (p < 0.001) increased the TBARS and, hence, the lipid peroxidation in cerebral and hepatic tissues of rats. Administration of endosulfan with doses of 10 or 15 mg/kg/d for 5 d has also induced lipid peroxidation significantly (p < 0.05). The same doses caused a significant alteration in glutathione redox status of cerebral and hepatic tissues, where total glutathione and oxidized glutathione were measured by an enzymatic cycling procedure. Selenium levels were also determined and compared with controls. With repeated doses, oxidant stress was more pronounced in cerebral tissue, where endosulfan shows a GABA-antagonistic activity. The possible relationship between the neurotoxicity of endosulfan and its oxidant stress-inducing effect was discussed. PMID- 7779564 TI - Catechin protection of 3T3 Swiss fibroblasts in culture under oxidative stress. AB - The effects of catechin, a well-known in vitro antioxidant, on 3T3 Swiss fibroblasts are studied under different conditions of oxidative stress leading to cell proliferation or cytotoxicity. Various levels of reactive oxygen species (ROS), generated extracellularly by the xanthine-xanthine oxidase (X-XO) system, are at the origin of the biphasic effect on DNA synthesis by 3T3 Swiss fibroblasts. The addition of 10(-2) U XO/mL, in the absence of exogenous X, catalyzes the production of low levels of O2-. and H2O2 in the extracellular medium, which stimulate DNA synthesis and cell division. The increase in the level of ROS, by addition of increasing X concentrations, did not enhance this effect proportionally. On the contrary, high levels of ROS inhibit DNA synthesis, the cytotoxicity induced being proportional to the level of H2O2 generated by the enzyme system. Catechin does not significantly modify DNA synthesis induced by low levels of ROS, but protects in a dose-dependent manner against the cytoxicity of high levels of ROS. PMID- 7779566 TI - Structure-activity relationship of flavonoids with superoxide scavenging activity. AB - The superoxide scavenging activities of 12 flavonoids were measured. The superoxide anions were generated by a hypoxanthine-xanthine oxidase system and measured by the nitrite method. The results showed that the scavenging ability enhanced with an increasing number of hydroxyl groups in ring B. Substitution at C3 position with a hydroxyl group increased the activity. Compared to a methoxyl group or a glycoside in this position, a free hydroxyl group showed the highest activity. A saturated C2-C3 bond showed a higher activity than a unsaturated bond. The absence of a carbonyl group at C4 position increased the activity. PMID- 7779567 TI - Effect of selenium supplementation on polyunsaturated fatty acids in rats. AB - The purpose of this work was to study plasma, adipose tissue, and liver fatty acids percentages of Wistar rats that drank water supplemented with several levels of sodium selenite for 1, 3, and 6 mo. In a general way, percentages of saturated, monounsaturated, and polyunsaturated fatty acids of supplemented groups were not different from those obtained with nontreated animals in the analyzed tissues. However, in rats supplemented with 0.5 ppm Se, mainly in adipose tissue, a polyunsaturated fatty acids increase (p < 0.005) was observed for all times of treatment. This could suggest that 0.5 ppm Se supplement probably exercises a protective role on polyunsaturated fatty acids in that tissue. Supplements of 6.0, 15.0, and 54.0 ppm Se did not change unsaturation levels of fatty acids in the analyzed tissues. PMID- 7779568 TI - Effect of selenium supplementation on some blood biochemical parameters in male rats. AB - The long-term effect of selenium supplementation on blood glutathione peroxidase (GSH-Px) activity and plasma TBARS' production (as an index of peroxidation) was evaluated in 15-mo-old male rats fed a diet supplemented with 0.25 or 0.50 ppm selenium, for 12 mo. A group of nonsupplemented age-matched rats was the control. In addition, triglycerides, phospholipids, total and free cholesterol, HDL cholesterol, and HDL-phospholipids levels were measured in plasma. Plasma testosterone levels were also determined in order to control the aging process in these animals. The GSH-Px activity and the peroxidation level were unchanged in all the groups. However, concerning the lipid parameters, a decrease in triglycerides concentration was observed in both treated groups (p < 0.05). Therefore, in these experimental conditions, despite no observed changes in parameters related to lipid peroxidation, selenium seems to be involved with triglycerides metabolism, eventually improving the triglycerides status of aged animals. PMID- 7779569 TI - Effects of selenium supplementation on thyroid hormone metabolism in phenylketonuria subjects on a phenylalanine restricted diet. AB - Type I 5'-deiodinase was recently characterized as a selenocysteine-containing enzyme in humans and other mammals. Up to now, the effect of selenium (Se) supplementation on thyroid hormone metabolism in humans has only been reported in the very peculiar nutritional environment of Central Africa, where combined severe iodine and Se deficiency occurs. In this study, a group of phenylketonuria subjects with a low selenium status, but a normal iodine intake were supplemented with selenium to investigate changes in their thyroid hormone metabolism. After 3 wk of selenium supplementation (1 microgram/kg/d), both the concentrations of the prohormone thyroxine (T4) and the metabolic inactive reverse triiodothyronine (rT3) decreased significantly. Clinically, the phenylketonuria subjects remained euthyroid before and after selenium supplementation. The individual changes of plasma Se and glutathione peroxidase activity were closely associated with individual changes of plasma T4 and rT3. PMID- 7779570 TI - Serum selenium levels in diabetic children. A followup study during selenium enriched agricultural fertilization in Finland. AB - The effect of increased selenium uptake on serum selenium in diabetic children was investigated during the first 9 yr of the Finnish nationwide selenium fertilization program, which started in 1984. Serum selenium concentrations were followed in 237 diabetic children (mean age 8.1 yr) and 214 controls from 1984 to 1992. The control group consisted of 107 siblings of the diabetics and of 107 other healthy children of corresponding age groups. Selenium was determined by direct electrothermal atomic absorption spectrophotometry. The effect of the increased uptake was seen in both diabetic and in control persons. Before the autumn of 1985, diabetic patients had significantly higher serum selenium levels than their siblings or the other healthy controls. Toward the end of year 1987, this difference had disappeared. After that, serum selenium levels continued to increase until the year 1990. In 1990 the mean selenium serum level of diabetic patients was 1.36 mumol/L and that of controls 1.33 mumol/L. The duration of diabetes did not have any effect on selenium serum levels. Slightly higher serum selenium in new diabetic patients before the start of therapy was explained by the dehydration state. The patients who were younger than 3 yr had slightly lower selenium serum levels when compared with older age groups. This difference was observed, however, only during the first 3 yr of the study. After that, when the selenium intake increased in general, no age-dependent differences were found anymore. There were no significant differences in serum selenium levels between males and females in either diabetic patients or in controls. PMID- 7779571 TI - Evaluation of selenium supply and status of inhabitants in three selected rural and urban regions of the Czech Republic. AB - Blood serum selenium of 65 men and hair selenium of 77 men from three regions of the Czech Republic (CR) were analyzed by neutron activation analysis, and 202 samples of urine from the same populations were analyzed for Se by the fluorimetric method to assess selenium status of these regions. Low status (53 micrograms Se/L of serum and 0.29 micrograms Se/g lyophilized hair as means) and very low urine selenium (8.7 micrograms/L urine) were detected. By these data, the CR is among the countries with the lowest Se intake. A comparison of studied regions is presented. Moreover, values of serum zinc were within the reference range, but mild to moderate deficiency in the supply of iodine was detected. PMID- 7779572 TI - Effect of iron and phagocytosis on murine macrophage activation in vitro. AB - Iron-exposed murine macrophages have a modified bactericidal activity as shown by previous observations. In order to assess the role of iron in macrophage activation, as measured by free radical production and by intracellular bacterial killing, murine peritoneal macrophages were cultivated in the presence of various sources of iron, human iron-saturated transferrin and ammonium ferric citrate, or iron chelators, Desferal, and human Apo-transferrin, and were infected with an enteropathogenic strain of E. coli. The release of nitrite (NO2-), and the production of superoxide anion (O2-) and hydrogen peroxide (H2O2) by the phagocytes were measured and compared to the production by uninfected macrophages. The synergistic action with murine r.IFN-gamma was also studied in the radical production reaction and for the bactericidal activity of macrophages. Our results show that in vitro phagocytosis of E. coli induced elevated production of NO2- and H2O2 by macrophages, and that oxygen derivatives were released independently of the presence of added iron or chelator. Despite a phagocytosis-related enhancement of NO2- release, reactive nitrogen intermediates (RNI) are not directly involved in the bactericidal mechanism, as revealed by increased intracellular killing owing to RNI inhibitors. Moreover, bacterial killing may depend on oxygen derivatives, as suggested by the effect of the antioxidant sodium ascorbate leading to both a diminished H2O2 production and a decreased bactericidal activity of macrophages. PMID- 7779573 TI - Seleno-lactobacillus. An organic selenium source. AB - Lactic acid bacteria are nonpathogenic bacteria commonly used in food processing. An evaluation was made of the capacity to concentrate selenium in species of Lactobacillus. A selenium concentration of 1 microgram/mL in the culture medium yielded in a bacterial content of 400 micrograms/g dry biomass. Dialysis and TCA precipitation experiments of a native intracellular extract proved that at least 80% of the total selenium is associated with organic molecules. Seleno-cysteine was identified as the only seleno-amino acid present in the intracellular selenoproteins. This study shows that species of the lactic acid bacteria are able to concentrate selenium intracellular as seleno-cysteine, which could be applied in supplementation studies. PMID- 7779574 TI - Effects of oral zinc gluconate on glucose effectiveness and insulin sensitivity in humans. AB - Zinc improves both insulin secretion and insulin sensitivity, and exerts insulin like effects. We investigated its acute effects on the parameters of glucose assimilation determined with the minimal model technique from frequent sampling intravenous glucose tolerance test (FSIVGTT) in seven healthy volunteers. FSIVGTTs (0.5 g/kg of glucose, followed by 2 U insulin i.v. injection at 19 min) were performed after the subjects had taken 20 mg zinc gluconate twice (the evening before and 30 min before the beginning of the test) or placebo pills (simple blind randomized protocol). Glucose assimilation was analyzed by calculating Kg (slope of the exponential decrease in glycemia), glucose effectiveness Sg (i.e., ability of glucose itself to increase its own disposal independent of insulin response), and SI (insulin sensitivity, i.e. the effect of increases in insulinemia on glucose disposal). The two latter parameters were calculated by fitting the experimental data with the two equations of Bergman's "minimal model." Zinc increased Kg (p < 0.05) and Sg (p < 0.05), whereas SI and insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, as evidenced by the increase in Kg, and that this improvement results mainly from an increase in glucose effectiveness (insulin-like effect), rather than an action on insulin response or insulin sensitivity. PMID- 7779575 TI - Effects of zinc on copper-induced and spontaneous lipid peroxidation. AB - Zinc (Zn) is an essential nonredox metal that has been regarded as having antioxidant properties. Some epidemiological indications and therapeutic results point to a role of Zn in restricting the development and the progression of some diseases. Redox-active metals like iron and copper are involved in oxidative injury mechanisms, and a decrease in the Zn:Cu ratio may be associated with certain pathologies. We studied the effect of Zn on the copper-induced lipid peroxidation in diluted human plasma. Lipid peroxidation was evaluated by measuring the formation of conjugated dienes and of thiobarbituric acid reactive products. We found that 20 microM Zn reduced the 125-microM copper-dependent formation of conjugated dienes by 27% and of thiobarbituric acid reactive products by 49%, during a 3-h incubation period. The inhibition of lipid peroxidation by 125 microM Zn is almost total in the same conditions. The time course study of the inhibitory effect of 125 microM Zn showed that it lasted for 7 h, which was the maximum incubation period tested. We also found that Zn had an inhibitory effect on the spontaneous lipid peroxidation in rat brain whole homogenates. Our results support the antioxidant properties of Zn, which may be potentially relevant to the protection of human plasma constituents, competing with the transition metals for redox reactions. PMID- 7779576 TI - Effect of aluminum and lead salts on lipid peroxidation and cell survival in human skin fibroblasts. AB - The aim of this study was to see whether aluminum (Al) and lead (Pb) salts are toxic for cultured human fibroblasts under different experimental conditions, in the controllable situation offered by cell cultures. Cell survival and membrane lipid peroxidation served as markers of Al and Pb toxicity. Evaluation of the living cells was carried out using a colorimetric method, the mitochondrial reduction of 1-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Lipoperoxidation assay was performed on whole cell homogenates by measuring thiobarbituric acid-reactive substances (TBARS) produced after incubation with ascorbic acid-ferrous sulfate. Al(III) and Pb(II) salts (300 microM) produce a considerable decrease in cell survival after an exposure period of 4d, evident with the three fetal calf serum concentrations in the culture media: 2, 5, and 10%. Taking into account in vitro cell aging, the cytotoxic effects of Al(III) and Pb(II) are greater in senescent fibroblasts than in young cells. Lead-induced cytotoxicity is higher than Al-induced cytotoxicity. A mechanism that contributes to cellular toxicity is membrane lipid peroxidation; our results demonstrate that Al(III) and Pb(II) ions, 400 microM, exert an antioxidant-like effect or a pro oxidant action on cell membranes depending on exposure time. We describe significant increases in TBARS formation associated with the presence of 400 microM Al(III) or Pb(II) salts in the culture media. Our study also revealed that these heavy metals induce a cell age-dependent action on membrane lipoperoxidation that is greater in senescent fibroblasts and this could have severe consequences for maintenance of cellular integrity. PMID- 7779577 TI - Antioxidant effect of vitamin E and glutathione on lipid peroxidation in boar semen plasma. AB - The protective effect of vitamin E and reduced glutathione (GSH) against lipid peroxidation in boar semen plasma was studied. The lipid peroxidation, measured by the test for thiobarbituric acid reactive substances (TBARS), doubled in the presence of the lipid peroxidation Fe(2+)-sodium ascorbate-inducing system. The ascorbate-induced TBARS were inhibited by about 62% through the water-soluble vitamin E analog (TROLOX) and about 57% by GSH. In the in vivo experiments, 7 wk of oral DL-alpha-tocopherol acetate (1000 IU/d/animal) administration caused a significant fall in the level of the semen plasma TBARS, from 2.2 +/- 0.09 to 1.2 +/- 0.13 nmol MDA/mL. The semen plasma superoxide dismutase (SOD) and GSSG tended to increase with the time of vitamin E administration, but the increment did not reach a significant level by the seventh week. The vitamin E supplementation significantly increased the number of spermatozoa per 1 cm3 of ejaculate. The protective role of vitamin E and GSH with respect to boar semen against fatty acid peroxidation and a positive influence of vitamin E supplementation on semen quality have been evidenced. PMID- 7779578 TI - Zinc deficiency does not enhance LDL uptake by P 388 D1 macrophages in vitro. AB - The aim of the study was to investigate the effect of zinc depletion on the susceptibility of Wistar rat low-density lipoproteins (LDL) to peroxidation and their uptake by macrophages, before and after in vitro oxidation. The rats were fed for 7 wk a Zn-adequate diet (100 ppm) ad libitum (AL), a Zn-deficient diet (0.2 ppm) ad libitum (ZD), or a Zn-adequate diet according to the pair-feeding method (PF). Zinc status was determined and, for each group, blood was pooled, and LDS were isolated and labeled with 125Iodine. An aliquot of each LDL sample was oxidized using FeII 10 microM/ascorbate 250 microM. Oxidized and nonoxidized (native) LDL were incubated with P 388 D1 macrophages, and their rates of uptake and degradation by macrophages were measured. Before oxidation, LDL uptake and degradation were not modified by the diet, suggesting that Zn deficiency did not modify rat LDL in vivo. After oxidation, both LDL uptake and degradation were significantly enhanced in the three groups. Nevertheless, we did not observe a significant effect of Zn deficiency. This observation suggests that, in our experimental conditions, Zn deficiency did not modify LDL catabolism. PMID- 7779579 TI - alpha-Tocopherol, ascorbic acid, and rutin inhibit synergistically the copper promoted LDL oxidation and the cytotoxicity of oxidized LDL to cultured endothelial cells. AB - Low-density lipoproteins (LDL) mildly oxidized by copper ions or UV radiations exhibit a cytotoxic effect to cultured endothelial cells. Rutin, a polyphenolic flavonoid, ascorbic acid, and alpha-tocopherol were able to inhibit the peroxidation of LDL and their subsequent cytotoxicity. The mixture of the three compounds (rutin/ascorbic acid/alpha-tocopherol, 4/4/1) exhibited a supra additive antioxidant effect. The inhibition of the cytotoxic effect was well correlated with that of TBARS formation. Another important conclusion is that these antioxidants were able to prevent directly at the cellular level the cytotoxic effect of oxidized LDL, since cells preincubated with them were protected against the cytotoxic effect of previously oxidized LDL. The protective effect of antioxidants was limited because of their own toxicity. The antioxidant mixture permitted a maximal cytoprotective effect with relatively lower concentrations to be obtained and the cytotoxicity of high concentrations to be avoided. In conclusion, rutin, ascorbic acid, and alpha-tocopherol constitute two lines of defense in protecting cells against injury owing to oxidation of LDL (1) at the LDL level, by inhibiting the LDL oxidation and the subsequent cytotoxicity, and (2) at the cellular level, by protecting the cells directly, i.e., by increasing their resistance against the cytotoxic effect of oxidized LDL. PMID- 7779580 TI - Microsomal membrane peroxidation by an Fe3+/paraquat system. Consequences of phenobarbital induction. AB - Descriptions of the effects of paraquat (P2+) on the peroxidation of liver microsomes are very divergent. Therefore, the presence of ferric iron in the medium and the activity of microsomal mixed-function oxidase system are two factors that we have taken into consideration to explain the discrepancies. The results showed that 100 microM P2+ potentializes the slight production of MDA induced by low concentrations of Fe3+ (< or = 15 microM). In these conditions, P+., arising from the one-step reduction of P2+ by NADPH-cytochrome C reductase, could reduce Fe3+ and cause the formation of species that initiate peroxidation. However, unlike the results obtained with CBrCl3, for animals induced by phenobarbital (Ph), the production of MDA in the presence of FeCl3 and of P2+ was weaker than for the controls. The establishment of a new Fe3+/Fe2+ equilibrium owing to increased production of P+. could be responsible. PMID- 7779581 TI - A site-directed mutant of Cu,Zn-superoxide dismutase modeled after native extracellular superoxide dismutase. AB - The well-studied cytosolic Cu,Zn-superoxide dismutase (SOD) protects against reperfusion injury, although its short (6 min) plasma half-life and negative charge create undesirable pharmacokinetics. We have designed, cloned, and expressed a genetic variant of SOD with altered pharmacological properties. A fusion gene consisting of the entire coding region of human SOD followed by a positively charged carboxy-terminal (C-terminal) "tail" of eight glycine and six arginine residues was constructed. The tail was modeled after the extracellular SOD (EC-SOD) C-terminal 26-amino acid basic peptide. This EC-SOD tail binds to heparin-like proteoglycans on cell surfaces and contributes to the enzyme's very long (30 h) plasma clearance time. After expression in Escherichia coli, the mutant enzyme was purified and characterized. No differences in specific activity or UV absorption spectrum between the mutant and the native enzyme were found. The thermal stability of the fusion protein was greater than that of native SOD. Although native SOD has no affinity for heparin, the modified enzyme bound to a heparin-agarose column. A "designer" SOD able to bind to cell surfaces may aid in the prevention of superoxide-mediated endothelial damage. PMID- 7779582 TI - Antimetabolites. PMID- 7779583 TI - New anticancer agents. PMID- 7779584 TI - Monoclonal antibody therapy of cancer. PMID- 7779585 TI - Gene therapy of cancer. PMID- 7779587 TI - Adoptive immunotherapy. PMID- 7779586 TI - Biological response modifiers. PMID- 7779588 TI - Alkylating agents. PMID- 7779589 TI - Differentiation agents in cancer therapy. PMID- 7779590 TI - Leukemias and myeloma. PMID- 7779591 TI - Lymphomas. PMID- 7779592 TI - Head and neck cancer. PMID- 7779593 TI - Lung cancer. AB - In SCLC, combination chemotherapy including agents such as etoposide, teniposide, cisplatin, carboplatin, doxorubicin, vincristine and cyclophosphamide continues to be the backbone of therapy. Epipodophyllotoxin derivatives, together with cisplatin or carboplatin are being increasingly used as part of the initial therapy. Complete plus partial responses to combination chemotherapy occur in 80 90% of all patients with a median duration of 9-11 months. Median survival in these studies is at present 11-16 months, depending on the initial tumour stage. At this point, 5-year survival is around 5% and includes a small fraction of patients (1%) initially presenting with extensive disease. The optimum duration of treatment is still uncertain, but the tendency is to shorten the duration of treatment to 6-9 months. The results of intensifying the treatment with the use of hematopoietic growth factors have hitherto been disappointing. The results of several phase II studies stress the importance of dose scheduling of etoposide in SCLC, with continuous treatment of 5 days' duration or more being superior. The therapeutic results for squamous cell carcinoma, adenocarcinoma, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these types of lung cancer should continue to be considered experimental, since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. PMID- 7779594 TI - Upper gastrointestinal tumors. PMID- 7779595 TI - Cancers of the large bowel and hepatobiliary tract. PMID- 7779596 TI - Mitomycin C. PMID- 7779597 TI - Endocrine tumors. PMID- 7779598 TI - Genitourinary malignancy. PMID- 7779599 TI - Gynecologic malignancies. PMID- 7779600 TI - Mitotic inhibitors. PMID- 7779601 TI - Breast cancer. PMID- 7779602 TI - Malignant melanoma. PMID- 7779603 TI - Soft tissue and bone sarcomas. PMID- 7779604 TI - Brain tumor chemotherapy. PMID- 7779605 TI - Malignant tumors of children and adolescents. PMID- 7779606 TI - Supportive care. PMID- 7779607 TI - DNA topoisomerase inhibitors. PMID- 7779608 TI - Cisplatin. PMID- 7779609 TI - Multidrug resistance. PMID- 7779610 TI - Role of human papillomaviruses in benign and malignant lesions. PMID- 7779611 TI - Mechanisms of invasion by head and neck cancers. PMID- 7779612 TI - Cellular and molecular mechanisms of radioresistance. PMID- 7779613 TI - Early detection and screening for head and neck cancer. PMID- 7779614 TI - Photodynamic therapy for cancer of the head and neck. PMID- 7779615 TI - Molecular phenotyping of head and neck cancer. PMID- 7779616 TI - Timing and sequencing of chemoradiotherapy. PMID- 7779617 TI - Organ preservation in advanced head and neck cancer. PMID- 7779618 TI - Elective modified neck dissection for treatment of the clinically negative (N0) neck. PMID- 7779619 TI - Distant metastases from head and neck squamous cancer: the role of adjuvant chemotherapy. PMID- 7779620 TI - Experimental therapeutic approaches for recurrent head and neck cancer. PMID- 7779621 TI - Head and neck cancer: the year 2000. PMID- 7779622 TI - Squamous differentiation and retinoids. PMID- 7779623 TI - Risk factors and genetic susceptibility. AB - Tobacco use is such a major determinant of head and neck cancer risk that classical epidemiologic techniques were more than adequate to document and characterize the etiologic association. However, the new emphasis in epidemiologic research is multidisciplinary, centering on the role of interindividual differences in susceptibility to carcinogenic exposures and particularly on the interaction of genetic susceptibility and environmental forces, that is, ecogenetics. For upper aerodigestive tract cancers, measurements of carcinogen metabolic activation and DNA repair capability are especially relevant. These susceptibility markers will enable the identification of high risk population subgroups who can be targeted for the most intensive primary and secondary preventive strategies. PMID- 7779624 TI - Biology and reversal of aerodigestive tract carcinogenesis. PMID- 7779625 TI - [The prognostic significance of the measurement of Ca 15-3 in the fluid of large breast cysts]. AB - Ca 15-3 was assayed in serum and in breast cysts fluid of 78 non neoplastic patients presenting Gross Cysts (GCD). In apocrine cysts and in the mixed type (serous and apocrine, class III) relapse was indicated by high serum and intracystic levels of the marker. Ca 15-3, therefore, may discriminate in a group of cysts a higher cellular resistance as well as an increased cell proliferation. Results suggest an important role of the marker in the follow up of patients with GCD and for the early detection of cyst relapse. PMID- 7779626 TI - [Diagnostic findings and the surgical treatment of liver metastases: our experience]. AB - The authors report their 10 year experience of 32 consecutive hepatic resections for metastases. All patients were preoperatively evaluated with US and CT, however, in 9 cases the diagnosis was obtained at laparotomy. In the first years there were no codified criteria for indications to surgery, while recently these were restricted, because of more favourable prognostic evaluations, to the metastases from colorectal carcinoma, endocrine or carcinoid tumours, digestive system neoplasms invading adjacent liver (in this case usually with palliative goal). The low mortality and morbidity registered explain the safety and efficacy of this procedure, also taking into account the fact that currently surgery is the only effective procedure with curative purpose. Criteria for patients selection, particularly in case of colorectal cancer, are referred and discussed and consequently prognostic factors are proposed: hepatic involvement extent, stage of primary tumour, absence of extrahepatic metastases, disease free interval between resection of primary tumour and hepatic resection for metachronous metastases. PMID- 7779627 TI - [Abdominal aortic aneurysm and rectal cancer: what surgical strategy?]. AB - The incidence of abdominal aortic aneurysm and colorectal cancer association is 0.5-1%. This concomitance of two potentially lethal diseases creates a decision making problem regarding priority of treatment. The Authors report a case in which colorectal cancer and abdominal aortic aneurysm were present. This patient first underwent surgery for colorectal cancer, then for aortic aneurysm. Moreover, the Authors review the Literature and discuss their decisional principles about treatment priorities. PMID- 7779628 TI - [The large hiatal stomach hernia and its surgical correction: the authors' personal experience]. AB - The authors report their experience with hiatus hernia surgery (9 cases of large hernia with severe gastroesophageal reflux). The fundamental role of instrumental diagnostics in establishing both a clear indication for surgical correction and the quality of the results obtained is emphasized. Technical details of the surgical treatment are report as well. On the basis of their experience and in accordance with other authors the Nissen fundoplication is considered a valid antireflux procedure. Furthermore, the abdominal approach used for this procedure allows to treat other abdominal pathologies often associated with hiatal hernia. PMID- 7779629 TI - [Primary acute acalculous cholecystitis]. AB - Acute acalculous cholecystitis (AAC) is a life-threatening condition whose incidence is steadily increasing although still lower than the corresponding lithiasic forms: AAC represents around 5-10% of all cases of acute cholecystitis. The severity of the disease is due to the rapid evolution towards gallbladder necrosis and biliary peritonitis. AAC is more frequently a disease of the critically ill patient arising in postoperative courses or in stressing conditions. Not rarely, however, it may occur with no evident predisposing factors and it seems related, in such cases, to elderly ages and to atheromatous vascular conditions. The authors report two cases of idiopathic AAC in elderly patients: pathogenic and clinical features as well as therapeutic options are analyzed and discussed. PMID- 7779630 TI - [The diagnostic-therapeutic picture in liver injuries: a review of the literature and clinical cases]. AB - Approximately 80% of liver trauma cases have a good prognosis and do not create decision-making problems for the surgeon, while in the remaining 20% the correct choice still represents a problem. Recently there has been a trend toward more conservative surgical management with emphasis on hemostasis and debridement, as well as a move toward a non-surgical alternative (surgical abstention) where feasible, relying in such cases on first-line CT scans for trauma evaluation. We report 51 cases of liver trauma observed in the period 1985-1993 graded according to the AAST Liver Injury Scale as follows: 12 grade I lesions (23.5%), 7 grade II lesions (13.7%), 19 grade III lesions (37.3%), 7 grade IV lesions (13.7%), and 6 grade V lesions (11.8%). In managing these cases we relied on two first-line diagnostic procedures: diagnostic peritoneal lavage (DPL) and CT scans. DPL, performed on 10 blunt trauma victims with unstable vital signs, was positive in 7 who thus underwent immediate surgery, and negative in 3 who subsequently underwent CT scan. Another 14 blunt trauma victims with stable vital signs underwent first-line CT scanning. In the event of a CT grade III or IV lesion patients underwent surgery, while patients with a CT grade I or II lesion were followed expectantly. Deaths (14) occurred only among patients with grade III or IV lesions (including 9 multiple trauma victims) who underwent surgery. PMID- 7779631 TI - [The physiopathology of carcinoids: current findings]. PMID- 7779632 TI - [Duplication of the gastrointestinal tract: a report of a rare case of mediastinal cyst]. AB - An unusual case of alimentary tract duplication located in the left anterior mediastinum and observed in a 37-year-old woman is reported. Resection of the lesion through a left thoracotomy approach was resolutive and followed by an excellent long term outcome. Etiology, diagnosis and therapeutic problems as well as differential diagnosis with benign and malignant chest lesions of adult population are briefly discussed. PMID- 7779633 TI - [Peroperative endoscopic papillotomy in a patient with an abdominal aortic aneurysm and biliary calculi]. AB - The authors report a case of abdominal aortic aneurysm associated with biliary tract lithiasis. The need to simultaneously treat both diseases is stressed. A technique which involves endoscopy during open surgery in order to prevent contamination is illustrated. The technique used together with other manoeuvres is part of a methodology aiming to broaden indications to the treatment of abdominal diseases associated with vascular diseases, limiting at the same time the risks of prosthetic infection. PMID- 7779634 TI - [The biological effects of the CO2 laser studied in experimental intestinal resections]. AB - An histological and E.M. study has been performed on rat's intestinal tract resection to evaluate CO2 laser effects. Necrotic effect of laser is evident up to 120 micron. While the intestinal tissue results normal at 480 micron from resection line. Muscular and fibrous components appear more resistant to damage while E.M. presents a new organization of its components forming a new compact and continue tissue. This new organization may be involved in the protection of the subepithelial spaces, and may have an important role in intestinal anastomosis scar process. PMID- 7779635 TI - [The current controversies over video laparoscopic cholecystectomy as the treatment of choice for cholelithiasis]. AB - Recently, the widespread use of laparoscopic cholecystectomy allowed to reach several goals such as a minimal invasive approach, a minimal operative trauma, the absence of aesthetic or functional damage of the abdominal wall, and a quick return to full activities. On the other hand, as all innovations, laparoscopic cholecystectomy is matter of debate and a number of controversies have recently appeared in the Scientific Literature. On the basis of their experience and through a critical review of the Literature, the Authors have therefore analyzed possible solutions to such controversies. Particularly, current indications and contraindications of this approach, surgical technique and relative sites of insertion of the trocars, the need to drain or not, the pre- and intra-operative study of the bile duct and the approach in case of bile duct stones pre- or intra operatively demonstrated, have been evaluated as possible answers. The Authors conclude that indications to laparoscopic cholecystectomy are the same of those for laparotomy, contraindications are represented by coagulopathies, liver cirrhosis and plastic peritonitis. At present it is still impossible to affirm which is the best surgical technique, the best position for the surgeon, and the best site for the insertion of the trocars, while drainage must be used only in those cases in which further manoeuvres on the bile duct are required. At last the Authors underline there is no need for a routine intraoperative cholangiography during laparoscopic cholecystectomy, however such technique must be known by laparoscopic surgeons since it may be mandatory in some selected cases. ERCP, on the contrary, is a valid support to laparoscopic cholecystectomy in the treatment of gallbladder stones associated with bile duct stones. PMID- 7779636 TI - Deliberate self-harm using yew leaves (Taxus baccata). PMID- 7779637 TI - Pseudotumour of the orbit: bilateral metachronous presentation. AB - A case is presented of a pseudotumour that developed in the left orbit 4 years after surgery and histological confirmation of a pseudotumour in the right orbit. There was no evidence of any thyroid pathology. PMID- 7779638 TI - Recurrent cerebral abscesses 20 years before recognition of multiple pulmonary arteriovenous malformations. PMID- 7779639 TI - Cutaneous SCC: metastases with a predilection for lungs 6 years after excision of the primary tumour. AB - An 80-year-old woman developed an ulcerated, moderately differentiated squamous cell carcinoma (SCC) on the lower leg. Despite local excision and radiotherapy, the patient presented 6 years later with multiple lung metastases which were histologically indistinguishable from the original skin tumour. There was no evidence of metastases to lymph nodes or other viscera. PMID- 7779640 TI - Candida albicans infection complicating percutaneous gastrostomy in cystic fibrosis. PMID- 7779641 TI - Dual-energy X-ray absorptiometry in rheumatoid arthritis: comparison between axial and appendicular skeleton findings. AB - Bone mineral density was measured by dual-energy x-ray absorptiometry (DXA) at the lumbar spine, both hips and distal radius in 10 postmenopausal patients with rheumatoid arthritis (RA). DXA values at the lumbar spine and distal radius were compatible with osteoporosis in all but 1 patient. Only 4 patients had osteoporosis of the hip, and 3 of these were over 65. Preliminary results over this small population suggest that in RA a correlation may be expected between DXA values in lumbar spine and distal radius, but not between either of these and the hip. PMID- 7779642 TI - HRT: another piece of the coronary jigsaw. PMID- 7779643 TI - HRT: a view from primary care. PMID- 7779644 TI - Do clinicians prescribe HRT for hypertensive postmenopausal women? AB - Despite the benefits of hormone replacement therapy (HRT) in relieving menopausal symptoms, there continues to be anxiety about its use in women who also have hypertension. To examine clinical practice in relation to HRT, especially in patients with hypertension, and to canvass opinions on potential or perceived side-effects, the authors conducted a postal survey of HRT prescribing habits among 285 GPs, physicians and obstetricians in the West Midlands. The overall response rate to the questionnaire was 191 (66.3%): 61 clinicians reported that they would not prescribe HRT in women whose hypertension was difficult to control, but only 3 would withhold treatment if blood pressure was well controlled; 9% of physicians and 13% of gynaecologists did not routinely measure blood pressure before starting HRT or monitor BP at follow-up (24% and 10% respectively). A proportion of GPs (20%), physicians (21%) and gynaecologists (9%) reported that in their opinion HRT raised blood pressure, and a minority in each group considered that HRT increased the risk of venous thrombosis, stroke and myocardial infarction. This study demonstrates differences among GPs, physicians and gynaecologists in the use of HRT in menopausal women with hypertension, the authors suggest that, in view of data from studies of the effects of HRT on blood pressure and the possible reduction of cardiovascular disease, these clinicians can be reassured and hypertensive women need not be denied the benefits of HRT, as long as there is careful monitoring. PMID- 7779645 TI - Comparison of clotrimazole, fluconazole and itraconazole in vaginal candidiasis. AB - Women attending a genitourinary medicine clinic (n = 229) with mycologically confirmed acute vulvovaginal candidiasis were randomised to receive either clotrimazole (500 mg pessary and 1% cream), fluconazole (150 mg single oral dose) or itraconazole (200 mg bd oral dose for 1 day). Mycological cure rates were 96% in the itraconazole group, 95% in the clotrimazole group, and 83% in the fluconazole group (P = 0.008). The proportion of patients who were clinically cured showed a similar pattern (itraconazole 80%, clotrimazole 80%, fluconazole 62%). This suggests that itraconazole or clotrimazole are more effective than fluconazole in the treatment of acute vaginal candidiasis. PMID- 7779646 TI - Gastrointestinal side-effects of NSAIDs in the community. AB - The prevalence of a range of gastrointestinal symptoms was compared in 1014 cases, identified in general practice, receiving chronic non-steroidal anti inflammatory drug (NSAID) treatment and 975 matched community controls. The NSAIDs being taken included aspirin (33%), ibuprofen (17%), naproxen (11%), piroxicam (9%), indomethacin (8%), and diclofenac (7%). The 12-month prevalence of dyspepsia in cases was 46% and in controls 43%, with no differences in symptoms prevalence between those taking aspirin and other NSAIDs or between individual NSAIDs. About one-third of the cases had consulted a GP about their symptoms and 7% had a co-prescription for an H2-receptor antagonist. Lower-bowel symptoms were more common in the NSAID-taking cases, particularly constipation and straining, and constipation was a more common reason for stopping medication than dyspepsia. PMID- 7779647 TI - Use of solvents to disperse ear wax. PMID- 7779648 TI - The effect of ranitidine on symptom relief and quality of life of patients with gastro-oesophageal reflux disease. AB - A 4-week study involving 354 patients with the symptoms of gastro-oesophageal reflux disease was conducted to assess the effect of ranitidine (as effervescent tablets) on their relief and quality of life. All patients received 150 mg bd for 2 weeks, with those responding to treatment continuing on the same dosage for a further 2-week period and 'non-responders' having the dosage increased to 150 mg qds for a further 2 weeks. Quality of life and symptom assessments were carried out at 0, 2 and 4 weeks. Two weeks' treatment with ranitidine 150 mg bd was effective at controlling the GORD symptoms in 78% of patients. A 4-week treatment with either 150 mg bd or qds controlled the symptoms in 85% of patients. All patients had significant improvements in all dimensions of their quality of life over the study period. PMID- 7779649 TI - Hyperventilation and dizziness: case reports and management. AB - Dizziness is a common symptom in patients presenting to an otorhinolaryngologist. Hyperventilation accounts for up to 5% of cases with dizziness and is a contributory factor in a further 20% of cases. Six cases of dizziness due to hyperventilation are presented to illustrate the author's simple management policy. A high index of suspicion in the absence of an organic cause of dizziness and a simple provocation test will identify these cases. Management is aimed at demonstrating resting hypocapnia, investigations to exclude organic causes of hyperventilation and rehabilitation in collaboration with a clinical psychologist ensures the appropriate treatment for the dizziness and can avoid the development of chronic somatisation behaviours. PMID- 7779650 TI - Screening and treatment for hyperlipidaemia in non-insulin-dependent diabetes: a prospective assessment of 350 patients. AB - This report presents experiences in screening 350 non-insulin-dependent diabetics for hypercholesterolaemia and results of 1 year's treatment. Mean serum total cholesterol was 6.4 mmol/l at screening; 46 patients whose initial total serum cholesterol was above 7.0 mmol/l attended for detailed assessment and treatment. Mean total cholesterol concentrations fell between screening and review (7.8 vs 7.1 mmol/l, P < 0.01). Levels fell below 7.0 mmol/l in 13 patients with diet alone. After excluding patients with secondary dyslipidaemia (including poor diabetic control), 10 patients received lipid-lowering drug treatment. Total cholesterol and triglyceride concentrations fell significantly and the HDL/non- HDL cholesterol ratio improved on treatment. Screening diabetic patients identifies a small group of hyperlipidaemic patients, whose lipoprotein profiles improve with drug treatment. Many of those screened, however, do not ultimately require drug treatment using a cut-off of 7.0 mmol/l. PMID- 7779651 TI - The metabolic and cardiovascular consequences of HRT. AB - Hormone replacement therapy comprises natural oestrogen and, when appropriate, progestogen given to postmenopausal women. Population studies have shown that postmenopausal oestrogen administration results in a marked reduction in cardiovascular disease, particularly coronary heart disease, an effect that does not appear to be lost when cyclical progestogen is also included. The way in which the hormones confer this protection has not been fully elucidated, but it includes effects on metabolic processes that contribute to atheroma formation as well as direct effects on the arteries themselves. Oestrogens and progestogens can produce beneficial changes in lipids and lipoproteins, glucose and insulin metabolism, body fat distribution, and coagulation and fibrinolysis. Oestrogen acts directly on blood vessels through both endothelium-dependent and calcium dependent mechanisms to improve arterial function. More widespread use of HRT could result in a major beneficial impact on cardiovascular disease, the leading cause of death in women. PMID- 7779652 TI - Selecting patients for HRT: positive indications. AB - As our understanding of the nature of modern postmenopausal hormone replacement therapy (HRT) has improved, the number of true contraindications to its use has declined. As a result, the question of whether or not to take HRT has become determined more by patient choice and less by medical factors, a trend that is likely to continue. Thus, women (as well as their doctors) need to be told of the indications for HRT so that they can make an informed choice. PMID- 7779654 TI - Polycythaemia rubra vera presenting with depression: recognising the syndrome abulia. AB - A patient with polycythaemia rubra vera is described, presenting primarily with symptoms attributed to depression. While in the ward she developed a stroke, confirmed on CT scan of the head. Venesection alone produced marked improvement in her neurological and psychiatric symptoms. The clinical picture corresponds most accurately to the neurological syndrome of abulia, which is an important differential diagnosis of depression with psychomotor retardation. The pathophysiology of impaired cerebral blood flow causing neuropsychiatric symptoms in polycythaemia is discussed. PMID- 7779653 TI - Miller Fisher syndrome and anti-GQ1b antibodies. AB - A case is presented of Miller Fisher syndrome in a 77-year-old woman. The diagnosis was confirmed by the presence of serum IgG antibody to ganglioside GQ1b. Miller Fisher syndrome, although uncommon, enters the differential diagnosis of brainstem stroke. PMID- 7779655 TI - Dieulafoy haemorrhage in association with polycythaemia rubra vera. PMID- 7779656 TI - The betrayers. PMID- 7779657 TI - Management of erectile disorder. PMID- 7779658 TI - The use of long-term acid-suppression therapy. AB - Drug therapy to suppress gastric acid secretion is commonly used in the management of dyspepsia, many patients taking such therapy over long periods of time. An audit of patients on long-term (> 12 months) acid-suppression therapy was carried out in the two practices providing primary healthcare to a town in Northeast England. Patients on continuous therapy (> 10 months' supply in the previous year) and intermittent therapy (6-10 months' supply in the previous year) were identified through computerised prescribing records. Their written and computer records were scrutinised to determine diagnosis, duration of therapy, use of NSAIDs and other features. A total of 365 patients were identified (208 men, 157 women): 132 were on intermittent and 233 on continuous therapy. Of the total, 83% were over 45 years and one-fifth were taking NSAIDs. Of the 310 patients investigated for their dyspepsia, only 250 had a positive diagnosis, of which duodenal ulcer (154) was the most common. PMID- 7779659 TI - Surgical patients with surprising laboratory data. AB - Preoperative laboratory tests were performed on elective ambulant orthopaedic patients (n = 26) on the afternoon after their arrival in hospital and on the next morning before the operation. Significantly lower concentrations of leukocytes, albumin, total protein, platelets, and total calcium were observed in samples taken in the morning. Posture and chronobiological rhythms may be responsible for these changes. An overnight change in laboratory values may lead to unnecessary further investigations and postponement of surgery. The clinician should be aware of the effects of preanalytical factors on laboratory data. PMID- 7779660 TI - Atrial fibrillation in the elderly: physicians' attitudes to anticoagulation. AB - The use of warfarin and aspirin for the primary prevention of stroke in elderly patients with atrial fibrillation (AF) is controversial. To establish current practice we circulated a questionnaire to 300 geriatricians (G) and 300 cardiologists (C). The response rates were 47% G and 51% C. Most physicians prescribed warfarin in AF associated with mitral stenosis (G vs C, 86% vs 89%, NS). Cardiologists were more likely to prescribe warfarin in AF associated with dilated cardiomyopathy (G vs C, 52% vs 86%, P < 0.01). A minority would prescribe warfarin in aortic valve disease and AF (G vs C, 37% vs 24%, P < 0.05) and lone AF (G vs C, 10% vs 26%, P < 0.01). Aspirin was favoured in aortic valve disease and lone AF. The cardiologists were less reluctant to use warfarin in the young and more likely to electrically cardiovert the young with chronic AF. PMID- 7779661 TI - Training and supervision of temporary transvenous pacemaker insertion. AB - To assess the current training and practice of central venous cannulation and temporary transvenous pacemaker insertion, a telephone survey of senior house officers (n = 60) and registrars (n = 20) was carried out in 80 acute hospitals in England and Wales. A median of one central line and two pacings were performed under supervision before the respondents were left unsupervised. The procedures were almost invariably taught at the bedside and usually by a fellow SHO or registrar. Virtually all the doctors surveyed were familiar with subclavian puncture, but experience with other routes was limited; 39/80 doctors questioned were unhappy about the training they had received, and 47 felt that formal training, such as tutorials or videos, would have helped. Training in central vein cannulation and temporary pacing needs to be more structured. This could be done by the use of videos or mannequins, and should include the use of routes other than the subclavian. PMID- 7779662 TI - Season of birth in Down's syndrome. AB - Previous studies have found a summer peak in the birth of individuals with Down's syndrome but have not tended to examine them into adulthood. The aims of this study were to look for evidence of a seasonal effect in birth and to uncover any differences in adulthood between those born in different seasons. The casenotes of all adults with Down's syndrome from the catchment area of a hospital for people with learning disability were examined. A summer peak in births was confirmed. Only 6% of births took place during January and February compared with the 17% expected (P = 0.019); birth during these 2 months was associated with female sex (P = 0.047). There was a trend for those born in December to March not to develop epilepsy (P = 0.053). PMID- 7779663 TI - Fluticasone propionate in the treatment of inflammatory dermatoses. AB - Fluticasone propionate is a new, topically active glucocorticoid which shows high specificity for the glucocorticoid receptor. After topical application systemic absorption is low. The small amount that is absorbed is rapidly and completely inactivated by esterase-catalysed hydrolysis in the liver. Even when applied in large doses under occlusion, there is no evidence of hypothalamic/pituitary/adrenal (HPA) axis suppression. Studies on skin thinning have shown no significant effect on skin thickness after once-daily application of fluticasone propionate 0.05% cream for 8 weeks. This cream has been shown to be highly effective in the treatment of eczema, and once-daily application shows no significant difference in efficacy compared with twice-daily treatment. Limited studies using 0.005% ointment in moderate to severe psoriasis showed similar efficacy to 0.1% betamethasone-17-valerate ointment. Fluticasone propionate 0.05% thus represents a major advance in topical corticosteroids. It has a high safety profile and the cream formulation is effective in a single daily application. PMID- 7779664 TI - New therapies for rheumatoid arthritis. AB - There are two major thrusts in the development of effective treatments in RA: the use and development of entirely new drugs; and the more effective usage of the currently available drugs. This represents a comprehensive review of the pharmacological agents that have been recently developed or will be available in the near future. PMID- 7779665 TI - Holistic approach to the management of erectile disorders in a male sexual health clinic. AB - A holistic view is given of the management of erectile disorders in a male sexual health clinic. Responsibility for the choice of treatment programme is shared with the patient, who makes informed consent. Involvement of the patient's partner is encouraged throughout. The increasing importance of good management for erectile dysfunction is indicated by the prevalence of the condition and the fact that, with a growing proportion of the population over the age of 65, it is age-related. PMID- 7779666 TI - Individualisation of HIV therapy: the clinician's perspective. AB - Assessment of clinical and laboratory markers of HIV infection may be used to individualise antiretroviral therapy. Data suggest that measures of viral load may be of considerable value as both a baseline and dynamic therapy marker, making these tools particularly useful in driving therapeutic decisions. Similarly, in-vitro data regarding intracellular pharmacokinetics and activity, resistance patterns and potential synergy of antiretroviral agents may be used to guide selection of optimal treatment regimens in clinical practice. PMID- 7779667 TI - Strategies for intractable ascites after hepatic resection: analysis of two cases. AB - Intractable ascites after hepatic resection is one of the gravest complications pertaining to deterioration in a patient's quality of life. Two cases are presented with intractable ascites that did not respond to ordinary conservative treatment after hepatic resection but were eventually successfully treated. The authors propose the following strategies: the conducting of aggressive and extensive examinations including angiography; and a peritoneovenous shunt for patients demonstrating no definite cause, to improve their quality of life. PMID- 7779668 TI - Volvulus of the stomach associated with colon in the chest. PMID- 7779669 TI - Primary peritonitis in a paraplegic patient. PMID- 7779670 TI - Non-convulsive status epilepticus as a complication of Mycoplasma pneumoniae infection. AB - Described is a confirmed case of non-convulsive status epilepticus, an unusual presentation of M. pneumoniae infection. The postulated pathological mechanisms in this infection are reviewed. PMID- 7779671 TI - Colonoscope incarceration within an inguinal hernia: a cautionary tale. AB - Incarceration of the colonoscope, within an undetected left-sided inguinal hernia, is a rarely reported event. The literature is reviewed, a possible mechanism described, and the technique used to remove the colonoscope outlined. PMID- 7779672 TI - Transection of the pancreatic head following blunt abdominal trauma. AB - Pancreatic trauma is rare, with a reported incidence of 0.4 per 100,000. Transection of the pancreas is extremely rare and usually involves the body region. An unusual case of pancreatic trauma, with complete transection through the pancreatic head, is described. PMID- 7779673 TI - Infected hydrocele complicating acute appendicitis. PMID- 7779674 TI - Severe hyperkalaemia due to mefenamic acid-induced hyporeninaemic hypoaldosteronism. AB - Described is a case of severe hyperkalaemia and hyporeninaemic hypoaldosteronism due to the inappropriate use of mefenamic acid. The causes of hyporeninaemic hypoaldosteronism are discussed and the importance of a detailed drug history emphasised. PMID- 7779676 TI - A complex true knot of the umbilical cord. PMID- 7779675 TI - Partial hypopituitarism in Klinefelter's syndrome. AB - A patient with Klinefelter's syndrome, secondary hypothyroidism and absent growth hormone and prolactin reserves is described. This combination of pituitary hormone deficiency has not been reported previously in association with Klinefelter's syndrome. PMID- 7779677 TI - Cor triatriatum: unusual cause of transient ischaemic attacks in a 67-year-old man. AB - Cor triatriatum is a rare congenital cardiac malformation, and in its most common form is characterised by a membrane that separates the left atrium into a proximal and distal chamber. First manifestation in adulthood has been reported previously, but at 67 years of age this patient is one of the oldest to present for the first time. It was diagnosed after a probable TIA, episodic vertigo and central retinal artery occlusion. The value of echocardiography in patients with neurological disease of presumed embolic origin is demonstrated here. PMID- 7779678 TI - Disability among older people: United States and Canada. AB - Data from two national surveys of community-dwelling people 55 years of age and over are the basis of tables presenting 25 measures of disability for each country. The report includes discussions of similarity and differences between the countries, methods used to make the data comparable, and limitations on interpretation of the data. PMID- 7779679 TI - The puzzle of Hox genes. AB - During the last few years, the regionalization of the rostral-caudal axis has been extensively studied through treatments with RA and genetic manipulations of Hox-C genes. RA shifts several Hox expression boundaries rostrally, deletes anterior rhombomeres but expands the caudal ones, and induces homeotic transformations in the vertebral column. These phenotypes indicate that retinoids may act in a graded fashion in the A-P axis, with maximum activity caudally. This excludes forebrain and midbrain, which apparently depend on neither Hox-C genes nor RA modulations, at least during early development. The phenotypes resulting from ectopic overexpression and loss of function of Hox genes described so far show homeotic transformations in paraxial mesoderm derivatives but not in the neurectoderm. An explanation for this discrepancy implies that the paraxial mesoderm may be already segmented in molecular terms at the time of Hox activation. Conversely, the activation of a distinct Hox-code without a previous "molecular segmentation" may specify rhombomeres with their own boundaries. This would explain why RA expands but does not duplicate the postotic rhombomeres. Finally, the atavistic transformations obtained by overexpressing Hox genes in the wrong place suggest that evolution might be introducing modifications within Hox regulatory regions. Thus, changes in their expression domains could sustain phylogenetic requirements. PMID- 7779680 TI - Tumor suppressor and overgrowth suppressor genes of Drosophila melanogaster: developmental aspects. AB - In Drosophila about 27 developmental genes have been identified which suppress tumorous growth and about as many genes are known to suppress overgrowth. Recessive lethal mutations in tumor suppressor genes block in one step the differentiation of specific target cells, leaving unaffected their capacity to divide in an autonomous, malignant and lethal fashion. The structural analysis of eight tumor suppressor genes predicts putative functions in differentiation events, such as cell-cell communication, protein transport and protein synthesis, signal transduction, sex determination splicing and cytokinesis. Their predicted products function as effectors of the differentiated state being vital components of cell junctions, the cytoskeleton, the protein synthetic apparatus, the splicing machinery and signal transduction. In contrast to the tumor suppressor genes, which are instrumental in the establishment and maintenance of the differentiated state, overgrowth suppressor genes seem to control cell-specific division rates while leaving unaffected the capacity of the cells to differentiate. The Drosophila tumor suppressor and overgrowth suppressor genes show clearly the mutual exclusion of the genetic programs controlling cell division and cell differentiation. Some of the genes exhibit homologies to mammalian genes. Their functional homology, however, is still an open question. PMID- 7779681 TI - Control of skeletal muscle-specific transcription: involvement of paired homeodomain and MADS domain transcription factors. AB - In the last few years, many aspects of skeletal muscle-specific gene regulation have been explained by the activity of the helix-loop helix (HLH) myogenic regulatory factors of the MyoD family, which are sequentially expressed during skeletal muscle formation. However, evidence is accumulating that muscle specific transcription requires functional interactions of these muscle-specific HLH factors with other regulatory proteins whose expression is not only restricted to skeletal muscle. These regulators include the SRF and MEF2 MADS domain and the MHox paired homeodomain transcription factors. Together with the aforementioned HLH factors, they build an increasingly complex network of regulatory factors. Two members of the Pax multigenic family of developmental control transcription factors, Pax-3 and 7, have been shown to be expressed not only in nervous tissue but also in skeletal muscle precursor cells. Their possible involvement in the control of muscle-specific transcription is discussed in light of known molecular properties of Pax gene products described in other biological systems. PMID- 7779682 TI - Expression of mesoderm markers in Xenopus laevis Keller explants. AB - In an attempt to document at the molecular level the behavior of mesodermal cells in Keller explant preparation, we have analyzed the time course of expression of four molecular markers of mesoderm gsc, Xbra, Xnot and XLIM-1. Our findings demonstrate that, (i) all mesodermal markers tested were expressed in the explants, but patterning of the mesoderm appeared incomplete; (ii) during convergence and extension of the explants, mesodermal cells did not invade the ectodermal tissue at any time tested, supporting the view that mesoderm establishes exclusively planar contacts with the ectoderm in this preparation; (iii) planar contacts were not sufficient to promote the neural expression of XLIM-1 protein in these explants. PMID- 7779683 TI - Widespread expression of the Xenopus homeobox gene Xhox3 in zebrafish eggs causes a disruption of the anterior-posterior axis. AB - The widespread expression of the Xenopus homeobox gene Xhox3 in zebrafish was performed by microinjection of synthetic Xhox3 mRNA into uncleaved fertilized eggs and resulted in embryos displaying varying degrees of anterior-posterior (A P) axis disruption. The phenotype observed was dose-dependent and showed anomalies, mainly in neural keel development, from microphthalmia to acephaly. Injection of 5 pg to 10 pg of mRNA caused a range of phenotypes in prim 5 stage embryos from normal to acephalic. Anomalies have been categorized according to an index of axis deficiency (Zf-IAD). We further characterized the axis disturbance by analyzing the expression of two genes implicated in axis formation: engrailed (eng) and brachyury (ntl). eng could not be detected in the muscle pioneer cells of embryos injected with Xhox3. The pattern distribution of brachyury (Ntl) protein is abnormal in Xhox3 injected embryos. Evidence for the conservation of the NH2 terminal region of the Xhox3 protein in frogs and fish is provided by the detection of a nuclear Xhox3-like protein in 24 h zebrafish embryos located in posterior mesoderm tissue. Previous results in Xenopus embryo research and the data presented here support the conservation of an A-P patterning mechanism involving the Xhox3 gene. PMID- 7779684 TI - Comparative analysis of Engrailed-1 and Wnt-1 expression in the developing central nervous system of Xenopus laevis. AB - Expression of the Engrailed-1 (XEn-1) gene was studied in Xenopus embryogenesis by Northern blot analysis and whole-mount in situ hybridization. One transcript of 2.2 kb was detected from stage 17 (midneurula) onwards, until stage 47 (swimming tadpole). The expression pattern of the XEn-1 gene as revealed by in situ hybridization can be divided in three regions. The first domain of transient expression appears at the midneurula stage (st. 17) in the anterior part of the neural fold, forming a complete ring of positive cells at the mid/hindbrain border after neural tube closure. A second region of transient expression is detected as groups of ventro-lateral cells in the spinal cord and the hindbrain from late-neurula till tadpole stages. A third area of transient expression of XEn-1 is formed by the anterior part of the developing pronephros. Comparison of XEn-1 expression at the mid/hindbrain border with that of the Xenopus wnt-1 and engrailed-2 genes reveals that XEn-1 and Xwnt-1, in contrast to XEn-2, are both detected in a narrow stripe of positive cells in this region. Analysis in exogastrulated embryos reveals that expression of XEn-1 and Xwnt-1, but not XEn 2, is induced by planar signaling in the presumptive midbrain. Of the three genes only XEn-1 is expressed in the floorplate at the mid/hindbrain border, while Xwnt 1 is expressed in adjacent cells in the neural ectoderm. The results suggest that in vertebrates at the interface between cells in the floorplate and in the paraxial neuroectoderm, at the limited region of the mid/hindbrain border, En-1 interacts with wnt-1 in a signaling pathway analogous to the engrailed/wingless signaling in the parasegments of the Drosophila embryo. PMID- 7779686 TI - Expression of Hox A11 in the limb and the regeneration blastema of adult newt. AB - Homeoproteins are functionally involved in pattern formation of developing systems and are potentially good candidates to regulate positional information during limb regeneration in the newt. Here we report the molecular structure of Hox A11 and its pattern of expression during the regeneration of adult newt appendages. The transcriptional unit of the gene is composed of two exons separated by an intron. Northern blots revealed two major transcripts; a size difference would result from using two different polyadenylation signals. Therefore, the gene would encode a single protein that is very homologous to other vertebrate counterparts. The pattern of expression of Hox A11 in the adult newt shows interesting findings in relation to limb regeneration. First, expression is found in both intact limb and tail, showing maintenance of expression of an important regulator of development in the appendages of the adult newt. Second, Hox A11 is expressed mainly in the muscle and the bone of intact limbs, two tissue fractions known to participate in blastemal fate determination. Third, the level of Hox A11 expression increases drastically in both limb and tail regeneration blastemas, suggesting that the population of expressing cells is preferentially recruited during blastemal formation. Finally, proximal blastemas (mid-humerus) significantly express higher levels of transcript compared with distal ones (mid-radius and ulna). These features of expression suggest that Hox A11 may participate in limb pattern formation by specifying positional information to the progenitor cells of the regenerate. PMID- 7779685 TI - Differential expression of two different homeobox gene families during mouse tegument morphogenesis. AB - The expression of six genes belonging to two different homeobox gene families was studied during the embryonic and postnatal morphogenesis of head and body regions of the mouse integument. The first family included the Otx1 and Otx2 genes, both related to the orthodenticle Drosophila gene and the second was represented by four members of the Antennapedia class HOX genes: Hoxc8 and three Hoxd genes, d9, d11 and d13. In situ hybridizations with 35S labeled antisense RNA probes were performed on head serial frontonasal sections, as well as entire embryo and postnatal tail longitudinal sections. The expression of these genes shows a differential spatiotemporal pattern along the cephalo-caudal axis. In 12.5-day and 15.5-day embryos, the Otx2 gene expression is restricted to the nasal epithelium and its associated glands, while the Otx1 transcripts are present in both nasal and facial integuments, including nasal glands and hair vibrissa follicles. The Hoxc8 expression first appears in skin at 14.5 days of gestation in the sternal region and is extended at 16.5 days to the thoracic ventral and lumbar dorsal regions. The Hoxd9 and Hoxd11 genes are only expressed in the caudal skin from 14.5 days of gestation. The Hoxd13 transcripts are the last to appear, 2 days after birth, and are limited to the last epidermal cells to differentiate, i.e. those of the hair matrix of the caudal pelage hair follicles. Taken together, these observations strengthen the hypothesis that different homeobox gene families specify the regional identity of the skin in the cephalic and body regions. PMID- 7779687 TI - Association of p34cdc2 kinase and MAP kinase with microtubules during the meiotic maturation of Xenopus oocytes. AB - p34cdc2 protein is found in prophase, metaphase and activated Xenopus oocytes at a similar level whereas its kinase activity oscillates within meiosis. Using an anti-PSTAIRE antibody that recognizes Xenopus p34cdc2, it was demonstrated that the major part of p34cdc2 was associated with microtubules isolated in vitro from Xenopus oocytes. Conversely, tubulin was recovered in association with p34cdc2 in p13-Sepharose pellets. The abundance of the fraction of p34cdc2 which was associated with microtubules did not oscillate during the meiotic maturation and the activation process. By contrast, the histone H1 kinase activity of p34cdc2 estimated in microtubular oocyte pellets was much higher in metaphase than in prophase oocytes. Cyclin B, which is associated in vivo with p34cdc2 in prophase and metaphase oocytes, was also present in the microtubular fractions. However, cyclin was not necessary for the binding of p34cdc2 to microtubules since p34cdc2 from activated eggs, where cyclin was missing, still copurified with microtubules. Purified MAP2, but not tubulin, was able to bind to p34cdc2, demonstrating that the association between p34cdc2 and microtubules was mediated by microtubule-associated proteins. During the meiotic maturation of Xenopus oocytes, several protein kinases were activated, among them MAP kinase. MAP kinase also associated with microtubules. It was demonstrated that both p34cdc2 kinase and MAP kinase purified from Xenopus oocytes were able to phosphorylate in vitro rat brain MAP2. However both protein kinases phosphorylated different domains of MAP2, suggesting that they might regulate microtubules in different ways. PMID- 7779688 TI - Distribution of TNF alpha-like proteins correlates with some regions of programmed cell death in the chick embryo. AB - Early chick embryos have previously been shown to express tumor necrosis factor alpha-cross-reactive proteins (TNF alpha-CRPs) in a developmentally regulated manner, thus implicating these proteins in programmed cell death and in tissue remodeling. In this study, cells undergoing DNA fragmentation have been identified, using terminal deoxynucleotide transferase (TdT) mediated dUTP-biotin nick-end-labeling (TUNEL), during the embryonic development of the chick, between stages 18 and 29. DNA fragmentation is indicative of cells undergoing programmed cell death. TUNEL-positive cells were identified in several well documented areas of programmed cell death, including the limb buds, the heart, spinal motoneurons, dorsal root ganglia, and the ventral horn of the neural tube. In addition, other areas of cell death were identified including the floor plate and the mesonephros. In several locations, a close correlation was noted between the presence of TUNEL-positive cells and regions of TNF alpha-immunoreactivity. These regions included the ventral horn and marginal zone of the neural tube, spinal motoneurons, paravertebral ganglia, parts of the myotome, mesenchyme of the body wall, and the mesonephros. In addition, using the TNF alpha-sensitive L929-8 bioassay it was shown that homogenate of stage 18 chick embryos is cytotoxic to L929-8 cells and that this toxicity can be reduced using neutralizing antibodies to mouse TNF alpha. This bioassay allowed us to estimate the mean concentration of TNF alpha-like activity in embryo homogenate, which is within the range of physiological (pg/ml) levels of TNF alpha found in other systems. These results suggest that proteins with TNF alpha-like activity may have a role in programmed cell death in some tissues during early chick embryo development. PMID- 7779689 TI - Hypertrophy is not a prerequisite for type X collagen expression or mineralization of chondrocytes derived from cultured chick mandibular ectomesenchyme. AB - Meckel's cartilage in the avian mandible is a neural crest-derived permanent cartilage. To investigate whether chondrocytes that form Meckel's cartilage can be induced to undergo maturation and mineralization by manipulating the environment, we used in vitro micromass culture in which young embryonic mandibular ectomesenchymal cells were maintained at a high cell density (2 x 10(7) cells/ml) and treated with ascorbic acid (AA) or with dexamethasone and ascorbic acid (DEX + AA). Chondrogenesis and chondrocyte maturation were analyzed by histological, immunohistochemical and SDS/PAGE techniques. Chick mandibular ectomesenchymal cells from Hamburger and Hamilton (J. Morphol. 88:49-92, 1951) stage 21 (HH stage 21) chick embryos undergo chondrogenesis forming cartilage nodules when maintained under micromass culture conditions. These chondrocytes undergo maturation in response to AA but not DEX. Addition of AA to culture medium induced type X collagen expression by these chondrocytes. With prolonged culture, chondrocytes began to mineralize turning cartilage nodules into completely mineralized structures. There was no correlation between chondrocyte size and type X collagen expression. Small chondrocytes as well as large (hypertrophic) chondrocytes expressed type X collagen and then underwent mineralization. Co-treatment of cultures with DEX + AA caused reduction of chondrogenesis and inhibited chondrocyte maturation and mineralization seen with AA alone. PMID- 7779690 TI - Immunofluorescent confocal analysis of tropomyosin in developing hearts of normal and cardiac mutant axolotls, Ambystoma mexicanum. AB - Tropomyosin is a major component of the thin filaments in organized myofibrils of cardiac muscle cells. A purported role for this protein is to prevent myosin thick filaments from interacting with actin thin filaments until the cell contracts. Recently, tropomyosin has been implicated in actin filament formation/stabilization as well. In the cardiac mutant axolotl, Ambystoma mexicanum, heart development is arrested. Mutant embryos form hearts that fail to beat due to a lack of organized sarcomeric myofibrils. There is also a concomitant reduction in the amount of tropomyosin in mutant heart cells. Previous studies have suggested that the addition of purified tropomyosin to glycerinated homogenates of mutant hearts causes amorphous actin to polymerize (or stabilize) into thin filaments. The current study was undertaken to examine the three-dimensional distribution of tropomyosin during myofibrillogenesis in normal hearts over the course of development from the heart-beat stage (35) through the advanced embryonic stage (41) and to investigate whether myofibrils form and/or significant quantities of tropomyosin accumulate in developing mutant hearts of comparable ages. PMID- 7779691 TI - Guidance of filopodial extension by fibronectin-rich extracellular matrix fibrils during avian gastrulation. A study using confocal microscopy. AB - We have used double-label confocal microscopy to examine the relationships between the orientation of filopodial extension in mesoderm cells and the orientation of fibronectin-rich extracellular matrix fibrils during chick embryo gastrulation. We fluorescently labeled mesoderm tissue dissected from donor embryos by immersion in carboxyfluorescein and then grafted it into unlabeled host embryos at the same stage of gastrulation. After further incubation, the host embryos were fixed, the endoderm removed, and the extracellular matrix was immunostained with antibodies to fibronectin conjugated to Texas Red. We found that both the general shape of the mesoderm cells and the orientation of filopodial extension were influenced by the surrounding matrix fibrils. Elongated shape was associated with individual fibrils which impinge on only one side of the cell. Similarly, filopodial extension followed a single fibronectin-rich fibril, although filopodia were also observed to be channeled between pairs of parallel fibrils. Cells attached to non-aligned regions of substratum showed no polarity. The mesoderm cells themselves apparently synthesize their own fibronectin, and deposit this on the cell surface not attached to the substratum. We conclude that individual fibronectin-rich substratum fibrils, in the size range 0.7-2.8 microns, are able to exert contact guidance on the mesoderm cells, despite the production of endogenous fibronectin by the cells themselves. These results support the contention that contact guidance is a physiological mechanism influencing the orientation and directionality of cells during the morphogenetic movements of embryogenesis. PMID- 7779692 TI - The emergence of an adult muscle phenotype in urodelan amphibians: an immunohistochemical study. AB - Electrophoretic techniques adapted for the analysis of muscles of lower invertebrates reveal four myosin heavy chain isoforms in the dorsalis trunci of Pleurodeles waltlii: two fast (MHC-IIA, MHC-IIB), and one slow (MHC-I) in the adult and one isoform (MHC-La) in the larvae. Polyclonal antibodies were prepared against the larval (anti-MHC-La) and one of the fast myosin (MHC-IIA) isoforms and their specificity was confirmed by western blot analysis. An immunohistochemical analysis was then carried out on frozen sections of the dorsalis trunci of P. waltlii at different stages of development. From stage 44 it was possible to demonstrate the presence of MHC-IIA in the small diameter fibers at the periphery of the muscle; the number and diameter of these fibers increased from stage 44 to stage 56 when anatomical metamorphosis had finished. By stage 56 these fibers could also be readily identified using standard histochemical techniques as type IIA fibers. We conclude that fast IIA myosin is expressed well before the final adult muscle phenotype has been established and its expression is therefore independent of thyroid hormone. PMID- 7779693 TI - Effects of age and genetic growth rate on the crystallin composition of the chick lens. AB - This two part study continues and extends our examination of the effects of age and of genetically determined intrinsic growth rate on the overall protein composition of chick lens epithelia, lens fiber masses and whole lenses. Water soluble proteins were analyzed by SDS-polyacrylamide and 2-dimensional gel electrophoresis. First, detailed age-related changes in protein expression between day 4 of embryonic development and the 8-week adult stage are described for one normal chick strain. Secondly, comparisons are made between day-old post hatch chicks of four different genotypes: two genetically unrelated chick strains with a high growth rate and propensity for hyperplasia of the lens epithelium and two unrelated slow-growing strains, both with normal lens morphology. We find that the beta/delta-crystallin ratio in lens epithelia and fiber masses is higher in both the slow- than in both the fast-growing strains. The data emphasizes the importance of quantitative and non-coordinate changes in crystallin polypeptide expression during lens growth and development, and implicates growth rate as a modifier of the pattern of crystallin expression. PMID- 7779694 TI - Preimplantation development of manipulated mouse zygotes fused with the second polar bodies: a cytogenetic study. AB - Immediately after fertilization one chromatid of each maternally-derived chromosome is extruded into the second polar body (2PB). We tested the ability of these "extra" chromosomes to support preimplantation development. Micromanipulation and electrofusion techniques were used to fuse 2PBs with diploid, haploid, or enucleated mouse zygotes. Androgenetic haploids, intact embryos, and digynic triploids served as the controls for the reconstructed embryos. Androgenetic haploid zygotes developed to the blastocyst stage only when fused with the 2PBs. This result demonstrates that even when extruded into the 2PB, chromosomes retain their ability to support normal preimplantation development. However, 2PB fusion with diploid zygote impaired preimplantation development. Normal development of experimentally produced digynic triploids (zygotes with one extra maternal pronucleus) indicated that developmental arrests, caused by the 2PB fusion, were not the result of triploidy or micromanipulation procedures. Cytogenetic studies showed that developmental failures of the reconstructed embryos were caused by premature chromosome condensation of the polar body chromosomes. This result indicates that 2PB must be removed from the zygotes' perivitelline space during animal cloning experiments. In addition, we showed that 2PB fusion with enucleated zygote is a reliable method for 2PB karyotyping and may be used in the studies of mammalian meiosis. PMID- 7779696 TI - Mononuclear leukocytes in the newt limb blastema: in vitro behavior. AB - Since the precise interactions of the various newt limb blastema cell types (pleiomorphic, bipolar, signet and multinucleated cells) with one another are difficult to ascertain in vivo, in this study we describe the in vitro behavior and interactions of these cell types with one another. The data show that the mononuclear signet cells interact (fuse) with other signet cells or fuse directly with the multinucleated cells. Further, they indicate that the signet cells are in fact mononuclear leukocytes and the giant cells are osteoclasts. Therefore, we conclude that these two cell types are not formed by dedifferentiation but are of hematopoietic origin and may play minor roles in blastema production. PMID- 7779695 TI - A reversible block at the G1/S border during cell cycle progression of mouse embryos. AB - Late 2-cell stage mouse embryos were cultured in M-199 plus 100 micrograms/ml Na pyruvate 25 micrograms/ml gentamycin and 0.3% BSA with or without mimosine (200 microM, 150 microM, 100 microM and 50 microM) for a short (4-5 h) or long (18-20 h) culture period; after drug removal subsequent embryo development was evaluated. Late 2-cell stage mouse embryos treated with mimosine were blocked at the 4-cell stage. Autoradiographic studies show that mimosine inhibits cell cycle progression in mouse embryos at the G1/S boundary. The onset of DNA replication occurs within 15 min of releasing the embryos from mimosine block. Embryos pretreated with mimosine at 200 microM and 150 microM for 4-5 h progress after 3 4 days in culture to hatched blastocyst (71% and 79%, respectively) compared with control (90%). However a longer pretreatment (18-20 h) with mimosine at 200 microM was significantly detrimental to the subsequent developmental progression to hatched blastocyst (2% vs 81%, p < or = 0.05); the proportion of degenerated embryos was significantly increased with mimosine at 200 microM and 150 microM compared with control (57% and 28% vs 4%, p < or = 0.05) after 3-4 days in culture. Preliminary studies with mimosine treatment at 100 microM and 50 microM for 18-20 h show that 70% and 37% of the embryos were blocked at 4-cell stage, respectively. These results indicate that mimosine inhibits cell cycle progress in mouse embryos at the G1/S border and thus induces a reversible arrest in a dose- and time-dependent manner. PMID- 7779697 TI - Virofection: a new procedure to achieve stable expression of genes transferred into early embryos. AB - A new procedure, virofection, designed to stabilize the expression of transfected DNA has been developed. It exploits the capacity of retroviruses to integrate their genome into the chromosomes of host cells. The co-transfection of two plasmids, one carrying the genome of a defective retrovirus vector, the other one encoding all the retroviral proteins, results in a transient production of infectious virus particles. These particles can infect the neighboring cells and this leads to the stable integration of the vector genome. This procedure is time saving and appears to be quite efficient. When applied to chicken embryonic fibroblasts cultured in vitro, it resulted in the stable expression of the lacZ gene in more than 30% of the cells, and did not induce chronic viremia. Stable lacZ expression was also achieved in chicken embryos in ovo. Virofection appears to be a promising and generally applicable method for implementing stable, safe and efficient gene transfer in vitro and in vivo. PMID- 7779699 TI - Can we improve the professional and personal fulfillment of doctors in cancer medicine? PMID- 7779700 TI - The recruitment of patients into clinical trials. PMID- 7779698 TI - Is neuroblastoma screening evaluation needed and feasible? AB - Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity. PMID- 7779701 TI - Does autocrine growth factor secretion form part of a mechanism which paradoxically protects against tumour development? AB - Autocrine growth factor secretion has classically been considered as a mechanism by which tumour cells achieve autonomous growth. However, there is now considerable evidence that autocrine circuits operate in the growth regulation of normal adult tissues. Here we consider the possible advantages to the normal epithelial cell of utilising such an external growth factor circuit and suggest that autocrine growth factor secretion, when viewed in a multicellular context, could paradoxically form part of a mechanism for preventing tumour development. PMID- 7779702 TI - Adjuvant therapy for operable breast cancer; more answers, new questions. PMID- 7779703 TI - The effect of dose and interval between 5-fluorouracil and leucovorin on the formation of thymidylate synthase ternary complex in human cancer cells. AB - We examined the importance of dosing interval between leucovorin (LCV) and 5 fluorouracil (5-FU) on intracellular thymidylate synthase (TS) ternary complex, free TS and total TS protein levels in human MCF-7 breast and NCI H630 colon cancer cell lines. A 2- to 3-fold increase in total TS was noted when either cell line was exposed to 5-FU 10 microM plus LCV (0.01-10 microM) compared with a 1.4- to 1.6-fold increase in total TS due to 5-FU 10 microM alone. The amount of TS ternary complex formed was 2- to 3-fold higher in both cell lines treated with the combination of 5-FU and LCV compared with 5-FU alone. TS complex formation and total TS protein increased with LCV dose (0.1-10 microM). In MCF-7 cells, the maximal increase in total TS protein and TS ternary complex formation was observed when 5-FU was delayed for 4 h after the start of LCV exposure. In NCI H630 cells, maximal total TS protein and ternary complex formation occurred when 5-FU was delayed for 18 h after the start of LCV exposure. The amount of free TS did not change in either cell line whether 5-FU was given concurrently with LCV or delayed for up to 24 h. The accumulation rate of intracellular folates in the form of higher glutamates Glu3-Glu5 was rapid in MCF-7 cells (maximal formation after 4 h), whereas in H630 cells accumulation of higher polyglutamates continued to increase up to 18 h. The time of peak folate polyglutamate (Glu3-Glu5) formation coincided with the time of peak TS complex formation and total TS protein in each cell line. In these human carcinoma cell lines, the LCV dose and interval between 5-FU and LCV play a role in increased TS total protein and TS ternary complex; however, the amount of free TS is independent of the interval between 5-FU and LCV. The time-and dose-dependent increases in TS ternary complex and TS total protein are associated with differences in the accumulation of folate polyglutamates in these cell lines. PMID- 7779705 TI - Thermal enhancement of both tumour necrosis factor alpha-induced systemic toxicity and tumour cure in rats. AB - In vitro and in vivo studies have suggested synergistic anti-tumour activity of combined hyperthermia and tumour necrosis factor alpha (TNF-alpha). However, some studies indicated an increased systemic toxicity of TNF by additional hyperthermia. The aim of this study was to obtain starting dosages for a clinical phase I study on the application of deep local hyperthermia and systemic TNF. We investigated the effect of local hyperthermia on the toxicity and efficacy of systemic TNF. Rats (Wag/Rij) carrying a subcutaneously transplanted osteosarcoma in the hind leg received a single intravenous dose of recombinant human (rh) TNF alpha, either at normothermia or at hyperthermia, by positioning the tumour bearing hind leg in a water bath of 43 degrees C. Dose-effect curves for lethality and tumour cure were established and LD50 and TCD50 values were calculated. Systemic toxicity was increased by local hyperthermia. The LD50 values (+/- s.e.) were 1088 (+/- 61) micrograms kg-1 at normothermia and 205 (+/- 23) micrograms kg-1 at hyperthermia, resulting in a thermal enhancement ratio (TER) of 5.3. Following normothermia, tumour cures were observed at TNF concentrations of 1000-1300 micrograms kg-1, while this was observed at doses of 50-300 micrograms kg-1 when combined with hyperthermia (TCD50 values of 1211 and 188 micrograms kg-1 respectively), resulting in a TER of 6.4. Systemic toxicity and anti-tumour activity of TNF are both increased by local hyperthermia. A safe starting dose for the combined clinical treatment would be 10% of the dose of TNF alpha that has been recommended for phase II studies on intravenous bolus administration of TNF-alpha at normothermia. In view of the large variability in tumour sensitivity for TNF-alpha, the clinical usefulness of this combined treatment modality has to be determined. PMID- 7779704 TI - Increased thymidylate synthase protein levels are principally associated with proliferation but not cell cycle phase in asynchronous human cancer cells. AB - We have analysed cell cycle variations in thymidylate synthase (TS) protein in asynchronously growing NCl H630 and HT 29 colon cancer and MCF-7 breast cancer cell lines. Western immunoblot analysis using the TS 106 monoclonal antibody revealed a 14- to 24-fold variation in TS levels between the peak exponential and confluent growth phase in the three cell lines. Similar variations in TS levels and TS activity were detected using the 5-fluorodeoxyuridine monophosphate and deoxyuridine monophosphate biochemical assays. The percentage of cells in S phase, which paralleled changes in TS levels, reached a maximum of 38-60% in asynchronous exponentially growing cells compared with 5-10% in confluent cells. In asynchronous exponential cells, analysis of TS levels in each cell cycle phase using two-parameter flow cytometric analysis revealed that TS protein levels were 1.3- to 1.5-fold higher in S than in G0/G1 phase cells, and 1.5- to 1.8-fold higher in G2/M than G0/G1 cells. Similar differences of 1.1- to 1.5-fold between G0/G1 and S-phase and 1.6- to 1.9-fold between G0/G1 and G2/M-phase were detected by Western immunoblot and biochemical assays. TS protein was not detectable by Western blot analysis, flow cytometry or biochemical analysis in the G0/G1 population of confluent cells. Twenty-six per cent of cells in this population were G0 cells compared with 2% in exponentially growing cells. In contrast to TS, a 4-fold difference in thymidine kinase (TK) was detected between G0/G1 and S phase cells in exponentially growing MCF-7 cells. The level of TS enzyme is associated with cellular proliferation and the percentage of cells in S-phase; however, TS protein is not exclusively associated with S-phase in asynchronously growing cells. The variation in TS levels between exponentially growing and confluent cell population appears to be due to differences in TS levels between G0 and G1 cells. PMID- 7779706 TI - Variation of growth rate of a rat tumour during a light-dark cycle: correlation with circadian fluctuations in tumour blood flow. AB - To determine whether tumour growth is influenced by circadian variations in tumour tissue blood flow, we measured changes in area doubling time of tumours (Sato lung carcinoma) within transparent chambers and changes in tissue blood flow of rat subcutaneous tumour during a light-dark cycle. Rats were subjected to an artificial light-dark cycle with light from 7 a.m. to 7 p.m. Tumour doubling times (TDTs) during the dark and the light spans were 33.5 +/- 11.9 h (n = 38, 20 rats) and 70.6 +/- 36.9 h (n = 39, 20 rats) respectively. The former was significantly shorter than the latter (P < 0.001). In addition, the larger the tumour became, the longer was the TDT during the light span (P < 0.05). Tumour tissue blood flow during the night (10 p.m.-4 a.m.) was approximately 1.5 times greater than that during the day (10 a.m.-4 p.m.). The time during which tumours actively grow and that during which tissue blood flow in tumours increases coincided. These results strongly suggest that tumour tissue blood flow is a determining influence on tumour proliferative activity and that tumour growth is influenced by circadian variations in tumour tissue blood flow. PMID- 7779707 TI - Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined. AB - The strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow rates of 50 to 200 ml min-1, but the effect was lost at 300 ml min-1. All flow rates also produced similar increases in relative perfusion of lung, of between 36% and 58%, and smaller increases in skin, of between 20% and 34%. The minimum breathing time at 150 ml min-1 to produce a significant increase in relative tumour perfusion was 4.5 min, and the effect was maintained up to 9 min. Nicotinamide alone at 1000 mg kg-1 60 min before assay did not alter relative tumour perfusion. Comparing the combination of nicotinamide with 6 min carbogen breathing at 150 ml min-1 with carbogen breathing alone showed no difference in relative tumour perfusion; increases were of 36% and 42% respectively. Nicotinamide-induced alterations in microcirculation associated with reduction of acute hypoxia have therefore not been detected by 86Rb extraction. The perfusion-enhancing effect of carbogen in this tumour is probably an important component of its radiosensitising ability, in addition to its known ability to increase the oxygen-carrying capacity of the blood, and should be taken into consideration in clinical studies. PMID- 7779708 TI - Flunarizine enhancement of melphalan activity against drug-sensitive/resistant rhabdomyosarcoma. AB - Flunarizine, a diphenylpiperazine calcium channel blocker, is known to increase tumor blood flow. It also interferes with calmodulin function, repair of DNA damage and drug resistance associated with P-glycoprotein. Flunarizine was tested for its ability to modulate either cyclophosphamide- or melphalan-induced growth delay for a drug-resistant rhabdomyosarcoma xenograft (TE-671 MR) and the drug sensitive parent line (TE-671), in which P-glycoprotein is not involved in the mechanism of drug resistance. Tumour blood flow was increased by 30% after a flunarizine dose of 4 mg kg-1, but no modification in growth delay was induced by melphalan (12 mg kg-1). In contrast, a 60 mg kg-1 dose of flunarizine had no effect on tumour blood flow, but the same dose created significant enhancement in melphalan-induced tumour regrowth delay in both tumour lines. The dose-modifying factor for flunarizine as an adjuvant to melphalan was approximately 2 for both tumour lines. Although blood flow measurements were not performed with the combination of flunarizine and melphalan, the results from flunarizine alone suggested that augmentation of melphalan cytotoxicity is not mediated by changes in blood flow. In contrast, flunarizine did not affect drug sensitivity to cyclophosphamide in groups of animals bearing the drug-sensitive parent tumour line. These results suggest that the mechanism of drug sensitivity modification by flunarizine is not related to modification of tumour blood flow, but may be mediated by modification of transport mechanisms that are differentially responsible for cellular uptake and retention of melphalan as compared with cyclophosphamide. PMID- 7779709 TI - In vitro anthracycline cross-resistance pattern in childhood acute lymphoblastic leukaemia. AB - Daunorubicin (DNR) is a major front-line drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Previously, we showed that in vitro resistance to DNR at diagnosis is related to a poor long-term clinical outcome in childhood ALL and that relapsed ALL samples are more resistant to DNR than untreated ALL samples. In cell line studies, idarubicin (IDR), aclarubicin (ACR) and mitoxantrone (MIT) showed a (partial) lack of cross-resistance to the conventional anthracyclines DNR and doxorubicin (DOX), but clinical studies in childhood ALL have been inconclusive about the suggested lack of cross resistance. In the present study we determined the in vitro cross-resistance pattern between DNR, DOX, IDR, ACR and MIT in 48 untreated and 39 relapsed samples from children with ALL using the MTT assay. The relapsed ALL group was about twice as resistant to DNR, DOX, IDR, ACR and MTT as the untreated ALL group. Thus, resistance developed to all five drugs. We found a significant cross resistance between DNR, DOX, IDR, ACR and MIT, although in some individual cases in vitro anthracycline cross-resistance was less pronounced. We conclude that IDR, ACR and MIT cannot circumvent in vitro resistance to DNR in childhood ALL. Clinical studies may still prove whether IDR, ACR or MIT has a more favourable toxicity profile than DNR. PMID- 7779710 TI - S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells. AB - Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel, cytotoxicity increased with progression through S and G2, peaked at the time of mitosis, and decreased thereafter. Maximum resistance to paclitaxel was in early S. Although lethal, brief exposure to docetaxel in S-phase did not delay progression through S and G2. Gross damage was detectable immediately after mitosis, with dysfunction in cytokinesis and accumulation of multinucleated, non-viable cells. Arrest of cells at prometaphase required continuous contact with lethal amounts of docetaxel or reintroduction of drug shortly before mitosis following pulse-chase treatment in mid-S-phase. Paclitaxel at moderate doses presumably acts mostly via damage to the mitotic spindle. In contrast, the available data suggest that docetaxel primarily targets centrosome organisation, leading to abortive mitosis and cell death. PMID- 7779711 TI - EO9: relationship between DT-diaphorase levels and response in vitro and in vivo. AB - EO9 [3-hydroxy-5-aziridinyl-1-methyl-2(1H-indole-4,7-dione)-prop-beta-en- alpha ol] was selected for clinical trial in Europe because of its preclinical profile but also because of its distinct mechanism of bioactivation. Several studies have shown that cells rich in DT-diaphorase may be particularly sensitive to EO9. The present study examined the relationship between DT-diaphorase activity and sensitivity to EO9 in a panel of cell lines largely derived from human and rodent leukaemias/lymphoma and solid tumours. A possible relationship between chemosensitivity and enzyme activity was demonstrated (correlation coefficient 0.796). A number of the human cell lines were established as xenografts in nude mice but, with the exception of HT29, DT-diaphorase specific activity was greatly reduced compared with the corresponding cell lines. These data suggest that in vitro studies of bioactivation of drugs by specific enzymes is unlikely to be relevant for the same tumour in vivo. Except for HCLO, all xenografts failed to respond to EO9 as a single dose. HT29 tumours in vivo had similar DT-diaphorase activity [359 nmol of 2,6-dichlorophenol-indophenol (DCPIP) reduced per min per mg of protein] to the cell line (337) but failed to respond to a single dose or daily dose schedule. A preliminary attempt to investigate an hourly dose schedule demonstrated a modest anti-tumour effect accompanied by enhanced toxicity. Attempts to optimise EO9 exposure parameters to potentiate activity in tumours with high DT-diaphorase activity are under way, but as yet the relevance of this particular enzyme for in vivo EO9 activity requires further investigation. PMID- 7779712 TI - Preclinical in vitro and in vivo activity of 5,6-dimethylxanthenone-4-acetic acid. AB - 5,6-Dimethylxanthenone-4-acetic acid (5,6-MeXAA) is a fused tricyclic analogue of flavone acetic acid (FAA) which was developed in an attempt to improve on the activity of FAA. Previous studies have shown 5,6-MeXAA to be curative in 80% of mice bearing colon 38 tumours and 12 times more dose potent than FAA. This investigation has demonstrated that a murine colon tumour cell line (MAC15A) is approximately 60 times more sensitive to 5,6-MeXAA than to FAA, although these differences were not seen in three human cell lines tested. 5,6-MeXAA caused significant blood flow shutdown and haemorrhagic necrosis in subcutaneous MAC15A tumours in syngeneic and nude hosts, but measurable changes in tumour volume were seen only in syngeneic hosts. 5,6-MeXAA was inactive against intraperitoneal MAC15A but produced significant anti-tumour effects against the same cell line inoculated via an intravenous route. FAA has been shown previously to be inactive in this model. Interestingly, the effects against lung colonies were not accompanied by obvious necrotic changes, suggesting that they may be the result of increased direct cytotoxicity rather than an indirect host mechanism. Further studies to investigate the effects against systemic tumour deposits are under way. PMID- 7779713 TI - Temporal heterogeneity in microregional erythrocyte flux in experimental solid tumours. AB - Using a multichannel laser Doppler system equipped with custom-developed microprobes, we have evaluated real-time fluctuations in microregional blood flow in two experimental murine tumour systems. The results show that in both the sarcoma F and the carcinoma NT over 50% of the microregions evaluated show a fluctuation in red blood cell flux by at least a factor of 2 over a 60 min time period. Approximately 20% of the regions monitored demonstrated a change in flow by a factor of 5 or more. Within the 1 h monitoring period, approximately 20% of the changes were reversed (SaF, 21%; CaNT, 19%). The duration of change for these regions ranged from 6 to 45 min. Similar temporal fluctuations in flow were seen in anaesthetised and unanaesthetised animals, indicating that artifacts due to probe movement were minimal. These findings clearly demonstrate that fluctuations in microregional erythrocyte flux are a common feature of the experimental tumours studied. PMID- 7779714 TI - Inhibitory effect of vanadium on rat liver carcinogenesis initiated with diethylnitrosamine and promoted by phenobarbital. AB - The chemoprotective effect of vanadium, a dietary micronutrient, against chemically induced hepatocarcinogenesis in rats was investigated. Initiation was performed by a single intraperitoneal injection of diethylnitrosamine (DENA; 200 mg kg-1) followed by promotion with phenobarbital (0.05%) in the diet. Supplementary vanadium (0.5 p.p.m.) in the drinking water was provided ad libitum throughout the experiment, before the initiation or during the promotion period. At the end of the study (20 weeks), vanadium supplementation throughout the experiment reduced the incidence (P < 0.01), total number and multiplicity (P < 0.001) and altered the size distribution of visible persistent nodules (PNs) as compared with DENA control animals. Mean nodular volume (P < 0.05) and nodular volume as a percentage of liver volume (P < 0.01) were also attenuated following long-term vanadium treatment. It also caused a large decrease in the number (P < 0.001) and surface area (P < 0.01) of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci and in the labelling index (P < 0.001) of focal cells, coupled with increased (P < 0.01) remodelling. The activity of GGT, measured quantitatively, was found to be significantly less in the PNs (P < 0.001) and non nodular surrounding parenchyma (P < 0.01) of vanadium-supplemented rats. The anticarcinogenic effect of vanadium was also reflected in the histopathological analysis of liver sections that showed a well-maintained hepatocellular architecture as compared with DENA control. Similar results were observed when vanadium was given only before the initiation. However, supplementation of vanadium during the promotion period did not result in significant alterations of these parameters. Our results, thus, strongly suggest that vanadium may have a unique anti-tumour potential which is primarily exerted on the initiation phase and only secondarily on the promotion stage. PMID- 7779715 TI - Abnormal pattern of post-gamma-ray DNA replication in radioresistant fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome. AB - Non-malignant dermal fibroblast strains, cultured from affected members of a Li Fraumeni syndrome (LFS) family with diverse neoplasms associated with radiation exposure, display a unique increased resistance to the lethal effects of gamma radiation. In the studies reported here, this radioresistance (RR) trait has been found to correlate strongly with an abnormal pattern of post-gamma-ray DNA replicative synthesis, as monitored by radiolabelled thymidine incorporation and S-phase cell autoradiography. In particular, the time interval between the gamma ray-induced shutdown of DNA synthesis and its subsequent recovery was greater in all four RR strains examined and the post-recovery replication rate was much higher and was maintained longer than in normal and spousal controls. Alkaline sucrose sedimentation profiles of pulse-labelled cellular DNA indicated that the unusual pattern of DNA replication in irradiated RR strains may be ascribed to anomalies in both replicon initiation and DNA chain elongation processes. Moreover, the RR strain which had previously displayed the highest post-gamma-ray clonogenic survival was found to harbour a somatic (codon 234) mutation (presumably acquired during culture in vitro) in the same conserved region of the p53 tumour-suppressor gene as the germline (codon 245) mutation in the remaining three RR strains from other family members, thus coupling the RR phenotype and abnormal post-gamma-ray DNA synthesis pattern with faulty p53 expression. Significantly, these two aberrant radioresponse end points, along with documented anomalies in c-myc and c-raf-1 proto-oncogenes, are unprecedented among other LFS families carrying p53 germline mutations. We thus speculate that this peculiar cancer-prone family may possess in its germ line a second, as yet unidentified, genetic defect in addition to the p53 mutation. PMID- 7779716 TI - Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer. AB - The retinoblastoma gene (Rb gene) is a tumour-suppressor gene and its product (pRB) is known to act as a negative regulator of the cell cycle. Although lack of pRB expression resulting from gene alterations is considered to be responsible for the genesis of several human malignancies, increased expression of pRB has been demonstrated in a majority of colorectal cancer cases. In the present study, we investigated the expression of pRB as well as that of its related kinases, cdk2 and cdc2, in colorectal cancer, since these kinases have been reported to phosphorylate and inactivate pRB. Western blot analysis revealed that colorectal cancer expressed higher levels of cdk2 and cdc2 than did normal mucosa and that the ratio of the hyperphosphorylated form of pRB was higher in colorectal cancer. Furthermore, immunohistochemical studies showed that cdk2/cdc2 was expressed exclusively in the cancer cells positive for pRB. These results suggest that an increase in the expression of cdk2/cdc2 in colorectal cancer may have prevented pRB from braking the cell cycle through phosphorylation. PMID- 7779717 TI - Immunohistochemical assay for epidermal growth factor receptor on paraffin embedded sections: validation against ligand-binding assay and clinical relevance in breast cancer. AB - Epidermal growth factor receptor (EGFR) has been the subject of much research since it was first described as a prognostic factor in breast cancer. The assay methods used and results obtained vary widely between studies. In this study 88 primary breast cancers were assayed for EGFR using a novel immunohistochemical assay performed on paraffin-embedded sections. The monoclonal antibody used was raised against purified, denatured EGFR, reacts with an epitope on the external domain and does not interfere with ligand binding. Twenty-two per cent of the tumours were EGFR positive using this assay. The results obtained were significantly correlated with those obtained by ligand-binding assay (r = 0.621, P = 0.011). The concordance rate was 82% (P < 0.001). The majority of discordant results could be explained by the presence of benign breast tissue and other non malignant elements which could be seen to express EGFR on the immunohistochemical assay and were excluded from the score for this, but would be incorporated into ligand-binding assay results. The well-established inverse relationship between EGFR (as measured by this assay) and oestrogen receptor (ER) was seen (chi 2 = 24.9, P < 0.0001). In addition, in this exploratory study on a limited tumour set, EGFR was a significant adverse prognostic factor (on univariate but not multivariate analysis) for both relapse-free survival (P = 0.02) and overall survival (P = 0.03) when measured by this immunohistochemical assay, but was not significant when measured by ligand-binding assay. PMID- 7779719 TI - p53 status of head and neck cancer: relation to biological characteristics and outcome of radiotherapy. AB - p53 status was investigated in 99 patients with squamous cell carcinoma of the head and neck region uniformly treated with accelerated radiotherapy and in whom tumour cell proliferation and DNA aneuploidy were assessed using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Seventy-six percent of tumours were immunohistochemically positive for p53 protein, but heterogeneity was noticed both in the percentage of cells positive for p53 and in their level of expression. However, tumours which were either essentially all positive or all negative or showed sporadic positivity for p53 protein showed no differences in their level of aneuploidy, proliferation rate, tissue organisation or outcome with radiotherapy. There was a trend for those p53-positive tumours with the strongest expression to have more DNA aneuploidy and deregulation of proliferation organisation than weaker expressors; but there were no differences in proliferation rate or outcome of radiotherapy. These studies suggest that p53 protein stabilisation as assessed by immunohistochemistry does not have any major relationship with the biological characteristics and outcome of squamous cell cancer treated by accelerated radiotherapy. PMID- 7779718 TI - Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions. AB - In vitro studies have demonstrated that fibronectin (FN) can deliver a mitogenic signal to quiescent human melanoma cells and that the alpha 5/beta 1-integrin receptor mediates this stimulus. In view of this finding we have analysed the in vivo expression of FN, and of ED-A and ED-B FN isoforms, in benign and malignant lesions of melanocyte origin. In the same specimens the expression of fibronectin integrin receptors was evaluated. The results demonstrate that, while detection of FN does not correlate with transformation and tumour progression, the expression of the two isoforms is associated with transformation and that only the ED-A variant is found in metastases. Integrin phenotyping disclosed that alpha 3/beta 1 expression is associated with tumour progression, alpha v/beta 3 is a marker of transformation, alpha 4 is rarely expressed and alpha 5 is expressed by about 50% and 30% of the primary and metastatic lesions respectively. Taken together, the results of this study demonstrate that transformation and tumour progression of the melanocyte lineage are associated with modulation of expression of FN isoforms and FN integrin receptors. Furthermore, the expression of alpha 5-integrin in a considerable percentage of primary and metastatic lesions indicates that FN may deliver a proliferative stimulus to melanoma cells in vivo. PMID- 7779720 TI - Absence of p53 autoantibodies in a significant proportion of breast cancer patients. AB - We analysed antibodies specific for human p53 in sera from primary breast cancer patients using three different immunoassays and we related these results to the p53 level in tumour tissue detected by immunohistochemistry. Only 44% (11/25) of apparently enzyme-linked immunosorbent assay (ELISA)-positive sera were from patients with a high level of p53 protein in more than 50% of their tumour cells. Surprisingly, 36% (9/25) of the sera originated from patients with no detectable p53 protein at all. Immunoprecipitation data suggested that the reason for this discrepancy is that at least some of the antibodies detected as positive in the ELISA in these sera from patients with clinical stage I and stage II breast cancers may be induced by immunogens other than p53 protein. Many of these reactions give apparently positive signals in a variety of p53 assays, and very stringent analysis is required to avoid possible misinterpretation of these responses as a p53-specific B-cell response in human cancer patients. PMID- 7779722 TI - Volunteers or victims: patients' views of randomised cancer clinical trials. AB - Randomised clinical trials are essential for the objective evaluation of different treatment strategies in cancer. However, in the field of oncology, very few of the eligible patients are entered into trials, and most treatments have only been tested on a small percentage of patients. For doctors, a major deterrent to participating in trials is the lack of resources--particularly time, but often also the local facilities. This report suggests that patients themselves are willing to take part in clinical research, and are attracted by being treated by a doctor with a specialist interest in the disease and encouraged by the possibility that their progress will be monitored closely. With the recent NHS changes, it is timely for the Department of Health and other national health departments to consider carefully what can be done to ensure that no new treatments are adopted without effective evaluation. This will require departments of health to identify and implement ways to facilitate accrual of appropriate numbers of patients onto research protocols (whether non-randomised phase I or phase II studies or large, multicentre phase III trials) over short time periods. PMID- 7779721 TI - Evaluation of p53 protein expression as a marker for long-term prognosis in colorectal carcinoma. AB - Mutation of the p53 gene is reported to be of prognostic importance in colorectal carcinomas. Immunohistochemical staining of the accumulated p53 gene product may be a simple alternative for p53 mutation analysis. Previous studies addressing the prognostic importance of p53 expression, however, yielded contradictory results. Therefore, we evaluated the importance of p53 expression as a marker for long-term prognosis in a well-characterised study population of 109 colorectal carcinomas. After antigen retrieval with target unmasking fluid (TUF), immunostaining of p53 was performed with both monoclonal antibody DO7 and polyclonal antibody CM1. Objective quantification of the p53 signal was assessed by a computerised image analyser. p53 expression was higher in non-mucinous tumours than in mucinous tumours (p53 labelling index = 30% and 17% respectively, P = 0.05), and in metastatic tumours compared with non-metastatic tumours (p53 labelling index = 37% and 22% respectively, P = 0.05). Other histopathological features were not related to p53 expression. In multivariate analysis, Dukes' stage (P = 0.02) and histological grade (P = 0.05) stood out as independent markers for prognosis. p53 expression was not an independent marker for prognosis. At present, p53 expression is not a useful marker for long-term prognosis. Further insight into the relationship between p53 mutations and p53 expression is needed to elucidate more precisely the clinical relevance of p53 alterations. PMID- 7779723 TI - Does it matter where you live? Treatment variation for breast cancer in Yorkshire. The Yorkshire Breast Cancer Group. AB - Over 27,000 patients with breast cancer were identified from cancer registry data from 1978 to 1992 and differences in treatment practice across the 16 districts of Yorkshire studied. A total of 50 surgeons treated more than an average of ten cases a year. Surgeons who expressed an interest in breast cancer were more likely to treat a greater number of patients than those who had no special interest in the disease and offered patients chemotherapy, hormone therapy and radiotherapy more often. The average regional mastectomy rate fell from 70% to 44% over this period, but the rate varied between districts from 13% to 87%, with those at the extremes occupying these positions year on year. The rate of uptake of radiotherapy varied between districts from 13% to 58% over the period 1978-92. The use of adjuvant chemotherapy increased from 5% to 19% and hormone therapy from 19% to 80% over this time period. An audit of the facilities available within each district carried out in early 1994 also showed considerable variation, although all districts now have access to a nurse specialist. There were wide variations in treatment offered to patients with breast cancer. Patients in some districts were denied access to chemo- and and radiotherapy despite published guidelines showing these modalities to be useful. It is recommended that patients are referred to units with an interest in breast cancer rather than to general surgical out-patients. PMID- 7779724 TI - CMF vs alternating CMF/EV in the adjuvant treatment of operable breast cancer. A single centre randomised clinical trial (Naples GUN-3 study). AB - The aim of this study was to test the hypothesis of Goldie and Coldman that the use of non-cross-resistant regimens of chemotherapy could lead to maximal anti tumour effect. We compared standard CMF (cyclophosphamide, methotrexate, fluorouracil) with alternating CMF/EV (epirubicin, vincristine) in the adjuvant therapy of early breast cancer. Stage II premenopausal node-positive or post menopausal node-positive oestrogen receptor-negative and stage III breast cancer patients were eligible for the study. From January 1985 to December 1990, 220 patients were randomised (115 to CMF and 105 to CMF/EV). Toxicity was mild; neurotoxicity, vomiting and hair loss were more frequent in the CMF/EV group, while permanent amenorrhoea, diarrhoea, stomach ache and minor infections occurred more often in the CMF arm. At a follow-up of 48 months, 113 patients (51.4%) had had recurrence (62 on CMF and 51 on CMF/EV) and 54 (24.5%) had died (30 on CMF and 24 on CMF/EV). There was no significant difference in disease-free and overall survival between the two arms. After adjusting for menopausal status and stage, the relative risk (RR) of recurrence for CMF/EV patients was 0.93 (95% CL 0.64-1.35), while the RR of death was 0.85 (95% CL 0.49-1.47). In conclusion, the Goldie-Coldman model of alternating therapy is not confirmed in this trial of adjuvant therapy of early breast cancer, although in view of its design a difference of less than 20% in 3 year disease-free survival could not be excluded. PMID- 7779725 TI - An evaluation of preoperative CA 15-3 measurement in primary breast carcinoma. AB - In this study of 500 patients with breast carcinoma, we have prospectively assessed the role of preoperative CA 15-3 as a marker of disease burden over a 7 year period. CA 15-3 levels at presentation correlate with stage of disease, tumour size, lymph node status, the presence of metastases and lymphocyte infiltration into the tumour. CA 15-3 alone is not an independent prognostic indicator, although a serum level of > 40 U ml-1 has a positive predictive value of 83% for the presence of advanced disease. We recommend the routine use of this marker in the preoperative assessment of primary breast carcinoma. PMID- 7779726 TI - Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study. AB - Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease. PMID- 7779727 TI - Microvessel quantitation in invasive breast cancer by staining for factor VIII related antigen. AB - The clinical importance of microvessel quantitation as a prognostic indicator in invasive breast cancer was examined. This study included 155 patients with invasive breast cancer, with a median follow-up of 82 months. Microvessels were identified by immunohistochemical staining for factor VIII-related antigen in formalin-fixed, paraffin-embedded primary tumours. For each tumour, microvessels were counted within a 200 x magnification field in the area of highest microvessel density. Microvessel counts (MVCs) had no correlation with tumour size, lymph node status or histological grade. When patients were classified by MVC, higher counts were associated with shorter disease-free survival and overall survival (P < 0.025 and P < 0.01 respectively). Multivariate analysis showed that MCV is an independent prognostic factor. Microvessel quantitation may be a useful predictor for identifying breast cancer patients at high risk for relapse and death. PMID- 7779729 TI - Platinum-Taxol non-cross resistance in epithelial ovarian cancer. AB - The aim of this study was to assess the clinical evidence for platinum-Taxol non cross-resistance in patients with epithelial ovarian cancer. Unlike other studies, only patients who had demonstrably progressive disease on platinum therapy were analysed. Patients received 135-200 mg m-2 of Taxol over 3 or 24 h and all patients were assessed for response by computerised axial tomography. The overall response rate was 22.2% (8/36 patients, 95% CI 10-39%). Only patients who received > or = 175 mg m-2 of Taxol responded (26.7%; 8/30 patients, 95% CI 12 46%). No complete responses were seen and the duration of response was short, median 7 months (range 5-9+). Response was associated with a short treatment-free interval (P = 0.02); only those who were treated immediately after they had progressed on their previous platinum therapy responded. Response duration was associated with a good performance status (P < 0.05). Platinum and Taxol are non cross-resistant in a proportion of patients and therefore patients who are resistant to platinum compounds may benefit from Taxol although the duration of any response is short. These data support current strategies that involve combining Taxol with platinum compounds as first-line therapy in advanced epithelial ovarian cancer. PMID- 7779728 TI - Phase II and pharmacokinetic study of lobaplatin in patients with relapsed ovarian cancer. AB - In phase I studies, lobaplatin showed activity in ovarian cancer patients pretreated with platinum. A phase II trial with lobaplatin was performed in patients with refractory or relapsed ovarian cancer to define activity and pharmacokinetics. Twenty-two patients were treated with lobaplatin administered as an intravenous bolus every 4 weeks. Dependent on creatinine clearance (CRCL) patients received 30 or 50 mg m-2 lobaplatin as the starting dose. Twenty-two patients received 78 courses (median 3, range 1-6). In eight patients total platinum (TPt) in plasma and urine, free platinum (FPt) in plasma ultrafiltrate (both measured by atomic absorption spectrometry) and lobaplatin in plasma ultrafiltrate measured (by high-performance liquid chromatography) were measured. Toxicity was confined to mild nausea and vomiting, mild leucocytopenia (WHO grade 3 in 18% of the courses), and renal function-related thrombocytopenia (WHO grade 3/4 in 53% of the courses). A correlation was found between CRCL and reduction in platelet count (r = -0.77; P < 0.01). No renal toxicity was encountered. Five of 21 evaluable patients (24%) achieved a response (four complete remissions and one partial remission). Remissions occurred mainly in patients who relapsed more than 6 months after primary treatment. The median survival from start of lobaplatin treatment was 8 months. The mean areas under the curve (AUCs) were 4.2 +/- 0.5, 3.0 +/- 0.6, and 3.2 +/- 1.1 h mgl-1 for TPt, FPt and lobaplatin respectively. The free platinum fraction (FPt/TPt) was initially very high, indicating low protein binding. FPt was essentially present as intact lobaplatin. Four hours after infusion 54 +/- 5% and 24 h after infusion 74 +/- 3% of the lobaplatin dose was excreted in the urine. In conclusion, lobaplatin is a platinum compound with anti-tumour activity in patients with relapsed ovarian cancer, especially in those who have platinum-sensitive tumours. The main toxicity of lobaplatin is thrombocytopenia and its dose should be corrected according to renal function. PMID- 7779730 TI - A pilot study of mitomycin, cisplatin and continuous infusion 5-fluorouracil (MCF) in advanced non-small-cell lung cancer. AB - A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non small-cell lung cancer (NSCLC). Of 31 patients assessable for response, one attained a complete remission and eight a partial remission, an overall response rate of 29%. Haematological toxicity was minimal, with only 3% of patients developing WHO grade III/IV neutropenia and 13% grade III/IV thrombocytopenia. Significant side-effects included moderate to severe emesis (41%), mucositis (34%), diarrhoea (31%) and palmar-plantar syndrome (14%). Seven patients (23%) had Hickman line complications requiring line removal. Continuous infusional chemotherapy with this regimen is active in advanced non-small-cell lung cancer, but its complexity and associated treatment toxicity offer little advantage over equally active but simpler and less toxic cisplatin-based regimens. PMID- 7779731 TI - Final report of a phase II study of interleukin 2 and interferon alpha in patients with metastatic melanoma. AB - Fifty-seven patients with metastatic melanoma were treated with interleukin 2 (IL 2) 7.8 MIU m-2 day-1 as a continuous infusion for 4 days combined with interferon alpha (IFN-alpha) 6 MIU m-2 day-1 subcutaneously on days 1 and 4. The cycle was repeated every 2 weeks for a maximum number of 13 cycles. Of the 51 evaluable patients, one (2%) achieved a complete and seven (14%) a partial response (total response rate 16%; CI 7-29%). Median time to progression and median survival were 2.5 and 11.3 months respectively. This regimen of IL-2 and IFN-alpha appeared to be only moderately active. PMID- 7779733 TI - Improving the acceptability of high-dose radiotherapy by reducing the duration of treatment: accelerated radiotherapy in high-grade glioma. AB - Radiotherapy, although clearly beneficial in patients with high-grade glioma, is largely palliative, and a protracted course of treatment may not be the most appropriate approach in the context of limited survival. We therefore assessed the feasibility, toxicity and survival results of a short accelerated radiotherapy regimen given twice daily over a period of 3 weeks. A total of 116 patients with high-grade glioma were treated with radiotherapy in a prospective study using an accelerated fractionation regimen. The total dose of 55 Gy was given in 32-36 fractions of 1.72-1.53 Gy, twice daily 5 days a week, with a minimum 6 h interval between fractions. Toxicity was assessed using Karnofsky performance status scale and in the later part of the study with the Barthel index. Survival data were compared with a control group treated with 60 Gy in 30 daily fractions in a previous MRC study, matched for known prognostic factors. The median survival of 116 patients treated with accelerated radiotherapy was 10 months. Survival comparison of accelerated patients with matched controls treated with conventional fractionation demonstrated a hazard ratio of 1.13 (95% confidence interval 0.85-1.51; P = 0.39). Early treatment toxicity was acceptable, with only seven patients developing transient decrease in performance status. The accelerated radiotherapy regimen was logistically feasible and acceptable to patients, carers and staff. Treatment time was reduced without apparent increase in early toxicity and there was no loss of survival benefit. The effectiveness and convenience of a short accelerated regimen makes this a suitable alternative to a 6 week course of radiotherapy in patients with high grade glioma. However, a full randomised trial comparing conventional and accelerated radiotherapy may be required as proof of equivalence. PMID- 7779732 TI - Quality of life following bone marrow transplantation: findings from a multicentre study. AB - Questionnaires assessing a range of quality of life (QOL) outcomes were completed by 200 adult bone marrow transplant (BMT) recipients from five BMT treatment centres. Respondents had undergone allogeneic (46%) or autologous BMT (54%) for a haematological malignancy and were disease free and at least 12 months post BMT (mean 43 months). Variability in post-BMT QOL was reported with deficits in physical, sexual and occupational functioning particularly likely. Allogeneic recipients reported poorer QOL than autologous recipients. Greater age at BMT, lower level of education and more advanced disease at BMT were consistent risk factors for poorer QOL. Contrary to previous research, evidence for improved functional status with the passage of time post BMT was obtained. Factors generally not associated with post-BMT QOL included disease diagnosis, dose of total body irradiation, presence of chronic graft-versus-host disease (GVHD), type of GVHD prophylaxis and extent of marrow graft match. In conclusion, while many BMT recipients reported normal QOL, the majority indicated that their QOL was compromised relative to premorbid status. Prospective, longitudinal research will be necessary to further identify risk factors for poor post-BMT QOL and identify the temporal trajectory of post-BMT QOL. PMID- 7779734 TI - Cancer in the offspring of survivors of childhood leukaemia and non-Hodgkin lymphomas. AB - Understanding the extent to which childhood leukaemia and non-Hodgkin lymphomas are heritable is important to the survivors of these diseases, their families and clinicians who provide genetic counselling. Such understanding is also relevant to the possibility raised by Gardner et al. (1990, Br. Med. J., 300, 423-429) that paternal preconception irradiation may be an aetiological factor in these diseases. No malignant neoplasm was diagnosed among 382 offspring of survivors of childhood leukaemia and non-Hodgkin lymphoma followed up for a median period of 5.8 years, the largest available cohort of such offspring. These data indicate that it is unlikely that the risk of a malignant neoplasm occurring in the offspring exceeds eight times that expected in the general population. Similarly, the risk of leukaemia and non-Hodgkin lymphoma among offspring is unlikely to exceed 21 times that expected. The proportion of survivors of childhood leukaemia and non-Hodgkin lymphoma with the heritable form of these diseases is unlikely to exceed 5%, assuming an autosomal dominant pattern of transmission, with penetrance of at least 70% and that all heritable cases develop by age 15 years. The best (i.e. at present most likely) estimates of these risks are of course much lower. There was no evidence of an excess of congenital abnormalities among the offspring and the sex ratio was similar to that expected from the general population. PMID- 7779735 TI - Endometrial and ovarian cancer and oral contraceptives--findings in a large cohort study. AB - Many case-control studies have shown that oral contraceptives protect against endometrial cancer and epithelial ovarian cancer, but little information is available from cohort studies. The findings from the Oxford Family Planning Association contraceptive study are reported here; the relative risks for ever users of oral contraceptives in comparison with never users were 0.1 (95% confidence interval 0.0-0.7) for endometrial cancer and 0.4 (95% confidence interval 0.2-0.8) for ovarian cancer. There was a strong negative relationship between duration of oral contraceptive use and ovarian cancer risk. Thus, in comparison with never users of oral contraceptives, the relative risk for users of up to 48 months' duration was 1.0 (95% confidence interval 0.4-2.5), while the relative risk for users of 97 months' duration or more was only 0.3 (95% confidence interval 0.1-0.7). PMID- 7779736 TI - Widowhood and divorce in relation to overall survival among middle-aged Norwegian women with cancer. AB - The aim of the study was to examine the relations between widowhood and divorce and overall survival among women with cancer. All Norwegian women born between 1935 and 1954, and diagnosed with cancer between 1966 and 1990, were followed up until 1991. In all, 14,231 cases were followed up for a median length of approximately 4.5 years (mean = 6 years), and 4311 women died during follow-up. In addition to overall cancer, separate analyses have been made for cancer at specific sites. Widows had a risk of dying which was nearly identical to that of married women for all sites except colorectal cancer, for which widows had a 2 fold increased death rate compared with married women. Divorced women had an overall increased hazard ratio of 1.17 (95% CI 1.07-1.27), which was confined to cancer of the breast, lung and cervix. With few clear exceptions women with children had a better survival than nulliparous women (overall hazard ratio = 0.80, 95% CI 0.74-0.87). PMID- 7779738 TI - Diet and breast cancer in Shanghai and Tianjin, China. AB - Various aspects of adult diet have been linked to breast cancer development. These include intake of fat (risk factor), and intake of fibre, soy protein and vitamins A, C and E (protective factors). Results of previous studies have been inconsistent. We examined the possible associations between breast cancer and various indices of nutrient and food intake in two Chinese populations who are at relatively low risk for breast cancer (one-fifth the rate in US white women). Two case-control studies of breast cancer were conducted in the cities of Shanghai and Tianjin, China. In Shanghai, 534 women aged 20-69 years with histologically confirmed breast cancer were recruited, whereas in Tianjin 300 women aged 20-55 years with histologically confirmed breast cancer were interviewed. All controls were community controls who were individually matched to the cases by sex and age (case-control ratio = 1:1). All interviews were conducted in person. Findings from the two studies were similar, although the diets in Shanghai and Tianjin were different in many respects. Cases and controls were similar in their consumption of soy protein, measured either in absolute levels or as percentages of total protein. Overall, all components of dietary fat (saturated fat, monounsaturated fat, polyunsaturated fat) showed a modest, non-significant association with breast cancer after adjustment for energy intake and other non dietary risk factors for breast cancer. Intake of crude fibre, carotene and vitamin C, on the other hand, exhibited strong, statistically significant inverse associations with breast cancer risk. The last three indices were highly correlated, rendering it impossible to disentangle their individual effects; they were closely associated with intake of green vegetables in the two study populations. Vitamin E intake was unrelated to breast cancer risk in Shanghai and Tianjin. In the multivariate logistic regression model which included all non dietary risk factors for breast cancer and energy intake, Shanghai women in the lowest tertile of crude fibre intake and highest tertile of fat intake had a 2.9 fold increased risk for breast cancer relative to those in the highest tertile of crude fibre intake and lowest tertile of fat intake. The comparable relative risk in Tianjin women was 2.4. Our data indicate a strong protective effect against breast cancer development with intake of foods rich in fibre, vitamin C and carotene. Our results are also compatible with dietary fat having a modest, positive effect on breast cancer risk within the range of exposure experienced by women in China.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779737 TI - Incidence, mortality and survival in cancer of the cervix in Bangalore, India. AB - Cancer of the cervix is the most common cancer among women in India, constituting between one-sixth to one-half of all female cancers with an age-adjusted incidence rate ranging from 19.4 to 43.5 per 100,000 in the registries under the National Cancer Registry Programme (NCRP) (Annual Reports, NCRP, ICMR). It has been estimated that 100,000 new cases of cancer of the cervix occur in India every year, and 70% or more of these are Stage III or higher at diagnosis. However, the incidence of cancer of the cervix as suggested in this report appears to be on the decline in Bangalore. Besides incidence and clinical stage at presentation knowledge of survival is essential to complete the picture of establishing baseline indicators to monitor and evaluate cancer control programmes. Survival analysis was carried out in 2121 patients diagnosed during 1982-89 in the population of Bangalore, India. The observed 5 year survival was 34.4% and the relative survival 38.3%. Clinical stage at presentation was the single most important variable in predicting survival. The 5 year observed survival for stage I disease was 63.3%, for stage II 44.0%, for stage III 30.3% and for stage IV 5.7%. PMID- 7779739 TI - Risk factors for male breast cancer. AB - Risk factors for male breast cancer were investigated in a case-control study of 21 cases and 82 controls admitted to hospital for acute, non-neoplastic, non hormone-related diseases in the Greater Milan area between 1988 and 1994. More educated men tended to be at higher risk of breast cancer, with a multivariate odds ratio (OR) of 2.6 [95% confidence interval (CI) 0.7-9.4]. The OR was 3.2 (95% CI 1.1-9.6) for those in the higher social class. Men with no offspring were at higher risk than fathers, with an OR of 5.5 (95% CI 1.8-16.7). A history of breast cancer in female relatives was reported by two cases and one control, giving an OR of 8.5 (95% CI 1.1-69.0). Cases were somewhat heavier than controls, and significantly taller, with an OR of 5.7 (95% CI 1.6-19.9) for subjects taller than 170 cm vs shorter ones. The association with weight, however, decreased after allowance for height, and no difference was observed for body mass index. Socioeconomic correlates and family history are similar to well-assessed risk factors for female breast cancer. The associations with anthropometric measures and childlessness may find an explanation in chromosomal abnormalities, such as Klinefelter's syndrome, or other hormone-related disorders. PMID- 7779741 TI - An overview of clinical and psychological research findings in anorexia nervosa. PMID- 7779740 TI - Cognitive and motor retardation in depression. AB - The study analysed the profile of psychomotor retardation in depression by clinically and psychometrically assessing its motor, speech and cognitive components. Psychomotor performance level of a group of 100 moderately depressed patients was significantly lower than that of controls on most psychometric tests. The interrelations among the variables evaluating various aspects of the depressive psychomotor retardation were examined and factor analyses were performed. Clinical ratings of motor, speech and mental retardation were strongly intercorrelated and a general factor emerged. When psychometric evaluations of depressive psychomotor retardation were factor analysed only separate factors characterizing cognitive and motor slowing were identified. Few and weak correlations were recorded between clinical and psychometric evaluations of depressive psychomotor retardation. Factors responsible for psychomotor slowing in depression were discussed. PMID- 7779742 TI - Neurosurgical stress and immune function. AB - The present study was carried out in 31 neurosurgical patients with unaffected consciousness and concerned by the severity of their condition. The severity of stress was established by the comparison between the pre- and postoperative peripheral blood lymphocyte populations and subpopulations (B, T, Th lymphocytes, serum complement and circulating immune complexes). The peripheral blood lymphocyte populations and subpopulations were determined by the technique of sheep red blood cell rosette. Circulating immune complexes were determined by precipitation of polyethylene glycol (PEG, M = 6000) whereas the serum complement by the usual 50% hemolytic method. Our data show that the decrease in Th cells and the consecutive diminution of antibody production is a cause of lower resistance against cancer and infections. PMID- 7779743 TI - Postoperative outcome of intracranial meningiomas; long-term prognosis. AB - A retro- and prospective study was carried out in 150 patients who underwent surgery for benign (grade I) intracranial meningiomas (ICM). The mean duration of the follow-up was of 4 years. The subjects were divided into 4 groups according to the intervals of follow-up examination. The following variables were analysed: preoperative (clinical and paraclinical diagnosis), operative (macroscopic investigation) and postoperative (complications, sequelae, recurrences). The data were statistically processed. Conclusions are drawn concerning early results as well as predictors of long-term prognosis. Immediate improvement of the neurological and mental status was noted in 51% of patients. Late favourable outcome was found in only 35% of patients, demonstrating a tendency of late worsening. Postoperative morbidity includes complications (21%), sequelae (32%) and recurrence (22%). Predictor criteria in operated ICM patients are: onset type of illness, preoperative score, tumor location, edema and excessive vascularization of the brain as inspected at operation, early and late sequelae. Histological predictors for recurrence are: nuclear pleiomorphism, cellular mitoses, cell agglomerations. The frequency of recurrence, regardless of the operative technique, demonstrates the tendency toward malignancy of many of these tumors. PMID- 7779744 TI - Acute hemiplegia in one infant. AB - A previously healthy 9-month-old girl, obese (12,500 gm) with sudden onset of hyperthermia (40 degrees C), generalized tonic-clonic seizures, followed by focal seizures, drowsiness, left facial nerve palsy, left lagophthalmos and mydriasis is presented. CT-scan and MRI suggested temporal-parietal infarction due to Sylvian artery occlusion in a 9-month-old infant with familial hypercholesterolemia (type 2 A dyslipidemia). The possibility of a cerebral abscess or herpetic encephalitis was considered. Negative clinic and serologic results excluded this diagnosis. The management of the symptomatology was made with parenteral antibiotics, anticonvulsive and antioedematous cerebral therapy. Favourable evolution with residual left hemiparesis after 30 days, when the child was discharged. CT-scan reevaluation (after 5 months of evolution) showed a hypodense temporal-parietal area abnormality due to a right ischemic infarction. PMID- 7779745 TI - The biology of nitric oxide. PMID- 7779746 TI - Option for surgical management of cerebral haematoma: case report. AB - A 48-year-old male patient, a surgeon, displayed a right temporo-occipital cerebral haematoma (5 x 7 cm). He had a history of chronic left occipital migraine-like cephalalgia from the age of 16 and hypertension was diagnosed when he was 42 years old. As therapy, he used ACE inhibitors, nifedipine and clonidine for hypertension and for cephalalgia a combination of aspirin, phenacetin and caffeine. During the last 2-3 months before the detection of cerebral haematoma, injections with piritramide were made when severe headaches were unbearable. The patient was operated on the 7th day since the onset of cerebral haematoma after a "wait and see" period of repeated clinical and CT-scan assessment. The initial option of the patient was surgical. We consider that the patient's profession (medical/surgical profile) may have played a positive motivation for the surgical option. PMID- 7779747 TI - Symptom distress, anxiety, depression, and discharge information needs after peripheral arterial bypass. AB - The purpose of this study was to describe the symptom distress, anxiety, depression, and discharge information needs of patients after peripheral arterial bypass surgery. Patients (n = 38) were interviewed before and after hospital discharge. The symptoms of incisional pain and broken sleep, as measured by Visual Analogue Scales, were the most distressing symptoms experienced before and after discharge. Patients reported low levels of anxiety and depression as measured by the Profile of Mood States. A moderate amount of information, assessed by the Patient Learning Need Scale, was perceived by patients to be important to help manage their care after discharge. The most important information related to the recognition, prevention, and management of complications. The findings contribute to an understanding of discharge information needs after peripheral arterial bypass and emphasizes the importance of patient education to facilitate transition to the home. PMID- 7779748 TI - The inclusion of women in clinical trials of antihypertensive medications: a review of twenty-four trials in one pharmacology journal. AB - Historically the inclusion of women in clinical trials of medications has been limited. To ascertain the inclusion of women in clinical trials of antihypertensive medications, an integrative review of 24 articles was undertaken. The articles were chosen from a representative journal of pharmacology from the years 1992 to 1993. Pharmacology journals frequently are the journal in which clinical trials of medications are published. All trials of antihypertensive medications in this journal from the years 1992 and 1993 were included. Analysis is made of inclusion and exclusion criteria, inclusion rates of women (22.4%), and the inclusion of the elderly and minority groups. Based on this review and others it is difficult to recommend generalization of antihypertensive medication guidelines to women on the basis of clinical trials that include few women. PMID- 7779749 TI - Clinical path coordinator: pulling it all together. AB - Institutions across the country are using different approaches to restructuring health care delivery systems. At Lehigh Valley Hospital collaborative practice was instituted to ensure the achievement of patient outcomes within appropriate time frames and with efficient use of resources. The role of the clinical path coordinator emerged from the collaborative practice model developed to manage the care of the patient with an abdominal aortic aneurysm. The step-by-step process for selecting, orienting, and implementing the role of the coordinator is discussed. Since the implementation of the coordinator role, patient satisfaction has been positive, length of stay and cost have decreased, and quality of care has improved for these patients. PMID- 7779750 TI - One vascular nurse's perspective on nursing roles in clinical research. PMID- 7779751 TI - A review: bedside nursing research. PMID- 7779752 TI - Splenic artery aneurysm. PMID- 7779753 TI - Carotid artery aneurysm. PMID- 7779754 TI - Tissue distribution, hormone regulation and evidence for a human homologue of the estrogen-inducible Xenopus laevis vitellogenin mRNA binding protein. AB - 17 beta-estradiol induces the synthesis of massive amounts of the hepatic mRNA encoding the Xenopus laevis egg yolk precursor protein, vitellogenin. Vitellogenin mRNA exhibits a half life of approx. 500 h when 17 beta-estradiol is present, and 16 h after removal of 17 beta-estradiol from the culture medium. We recently reported that Xenopus liver contains a protein, which is induced by 17 beta-estradiol and binds with a high degree of specificity to a binding site in a segment of the 3'-untranslated region (3'-UTR) of vitellogenin mRNA implicated in 17 beta-estradiol stabilization of vitellogenin mRNA. To determine if this mRNA binding protein was specific to this system, or if it was present elsewhere, and regulated by other steroids, we examined the tissue distribution and androgen regulation of this protein. Substantial amounts of the vitellogenin 3'-UTR binding protein were found in several Xenopus tissues including testis, ovary and muscle. In the absence of hormone treatment, lung and intestine contained minimal levels of the mRNA binding protein. Testosterone administration induced the vitellogenin 3'-UTR RNA binding protein in several tissues. Additionally, we found a homologous mRNA binding protein in MCF-7, human breast cancer cells. Although the MCF-7 cell protein was not induced by 17 beta-estradiol, the MCF-7 cell mRNA binding protein appears to be closely related to the Xenopus protein since: (i) the human and Xenopus proteins elicit gel shifted bands with the same electrophoretic mobility using the vitellogenin mRNA 3'-UTR binding site; (ii) The human and Xenopus proteins exhibit similar binding specificity for the vitellogenin 3'-UTR RNA binding site; and (iii) RNA from MCF-7 cells is at least as effective as RNA from control male Xenopus liver in blocking the binding of the Xenopus and human proteins to the vitellogenin mRNA 3'-UTR binding site. Its broad tissue distribution and regulation by both 17 beta-estradiol and testosterone suggests that this mRNA binding protein may play a significant role in steroid hormone regulation of mRNA metabolism in many vertebrate cells. PMID- 7779755 TI - Expression of sex hormone-binding globulin mRNA in human endometrial cancers. AB - To more fully understand the role of sex hormone-binding globulin (SHBG) on the intracellular steroidal action in endometrial cancers, we investigated the expression of SHBG mRNA as the substitute of SHBG expression in human endometrial cancers. In the present study, the levels of SHBG mRNA were analyzed using competitive reverse transcription-polymerase chain reaction (RT-PCR)-Southern blot analysis. The higher level of SHBG mRNA tended to be expressed in the normal secretory and late proliferative phase endometrium > early proliferative phase endometrium > well differentiated adenocarcinoma of the endometrium (G1) > moderately differentiated adenocarcinoma (G2) > poorly differentiated adenocarcinoma (G3), in the order shown. These studies indicate that endometrial cancer cells might synthesize intracellular SHBG to conserve their estrogen dependent properties. Further, it indicates that endometrial cancer cell synthesis of SHBG mRNA is lost as these cells undergo de-differentiation. PMID- 7779756 TI - Stable expression of rat cytochrome P450 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in MA-10 cells. AB - Glucocorticoids and mineralocorticoids are synthesized in the adrenal cortex through the action of two different cytochrome 11 beta-hydroxylases, CYP11B1 (11 beta-hydroxylase) and CYP11B2 (aldosterone synthase) which are distributed in the zona fasciculata and glomerulosa, respectively. We have created stably transfected cell lines using the Leydig tumor cell line MA-10 with CYP11B1 and CYP11B2 cDNA-containing plasmids which have a selectable gene to confer resistance to geneticin. The expression of the transfected cDNA in the cells was characterized by Northern-blot and measurement of enzymatic activity. The cell lines express the enzymes stably for many generations. CYP11B1 transfected cells converted DOC into corticosterone, 18-OH-DOC and small amounts of 18-OH corticosterone, in a time and concentration dependent manner. Incubation of the cells with corticosterone generated 18-OH-corticosterone especially at concentrations of 30 and 100 microM. The production of 18-OH-corticosterone from corticosterone at these doses was significantly higher than incubations with similar concentrations of DOC. CYP11B2 transfected cells converted DOC into corticosterone, 18-OH-corticosterone, aldosterone and small amounts of 18-OH-DOC in a time and concentration dependent manner. They converted corticosterone into 18-OH-corticosterone and aldosterone in a time and concentration dependent manner. The absolute and relative production of aldosterone from DOC was significantly higher than when cells were incubated with corticosterone, and the ratio of aldosterone to 18-OH-corticosterone was higher at all concentrations of DOC compared to corticosterone. CYP11B2 transfected cells (but not the CYP11B1 transfected cells) transform 18-OH-DOC into 18-OH-corticosterone, but can not convert 18-OH-DOC into aldosterone. In conclusion, stably transfected MA-10 cells with the cDNAs for the CYP11B1 and CYP11B2 enzymes were prepared and their enzymatic activity studied. These cells are useful in the study of inhibitors of the specific enzymes, as well as determining the roles that each enzyme plays in zone-specific steroidogenesis in the adrenal cortex. PMID- 7779757 TI - Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase. AB - A distinct human estrogen sulfotransferase (hEST-1) cDNA has been isolated from a human liver lambda Zap cDNA library using a PCR procedure. The enzymatically active protein has been expressed in two bacterial expression systems and the kinetic and immunologic properties of the enzyme have been characterized. The full-length cDNA for hEST-1 is 994 base pairs in length and encodes a 294 amino acid protein with a calculated molecular mass of 35,123 Da. Purified hEST-1 migrated with an apparent molecular mass of 35,000 Da during SDS-polyacrylamide gel electrophoresis. Immunoblot analysis of hEST-1 expressed in E. coli with a rabbit anti-hEST-1 antibody yields a band of approximately 35,000 Da. The anti hEST-1 antibody also detects a single band in human liver and jejunum cytosol which migrates with the same molecular mass as expressed hEST-1. There was also no cross-reactivity of hEST-1 with rabbit anti-hP-PST or rabbit anti-hDHEA-ST antibodies upon immunoblot analysis. hEST-1 was expressed in bacteria and purified to homogeneity. Expressed hEST-1 activity has a significantly greater affinity for estrogen sulfation than that found for the other human STs which conjugate estrogens. hEST-1 maximally sulfates beta-estradiol and estrone at concentrations of 20 nM. hEST-1 also sulfates dehydroepiandrosterone, pregnenolone, ethinylestradiol, and 1-naphthol, at significantly higher concentrations; however, cortisol, testosterone and dopamine are not sulfated. The results presented in this paper describe the expression and characterization of a human EST distinct from other human STs which sulfate estrogens. The high affinity of hEST-1 for estrogens indicates that this ST may be important in both the metabolism of estrogens and in the regulation of their activities. PMID- 7779758 TI - Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues. AB - The ability of breast tumours to synthesize hormones is well recognized, and local production of sex steroids is thought to play a role in breast cancer growth. We measured the intratumour and circulating levels of testosterone, dihydrotestosterone (DHT) and oestradiol in 35 histologically confirmed carcinomatous mammary tissues obtained at breast surgery from 34 postmenopausal patients, age 50-85 years. Intra-tissue steroids were extracted with ethanol:acetone (1:1; v/v), defatted with 70% methanol in water, and extracted with ether. Steroids, from tissue and serum, were separated by partition chromatography on celite columns and were measured by RIA. Intratumour testosterone and DHT concentrations were significantly correlated, after the exclusion of an outlier (rs = 0.71; P = 0.0001). No association was found between oestradiol and either of the two androgens. Mean oestradiol and DHT concentrations were significantly higher in tissue than in blood (P = 0.0001). Mean testosterone levels in tissues did not significantly differ from those measured in blood. Our data suggest that at least a part of intratissue DHT is produced locally from testosterone. The meaning of high oestradiol and DHT levels in cancer tissue still needs to be defined. PMID- 7779759 TI - Synthesis and biological activities of thioether derivatives related to the antiestrogens tamoxifen and ICI 164384. AB - The catalyzed coupling reaction of activated alcohol and mercaptan was used for the short and efficient synthesis of 14 thioether compounds. Two types of side chains, the methyl butyl alkylamide related to the pure steroidal antiestrogen ICI 164384 and the dimethylamino ethyloxy phenyl related to the clinically used nonsteroidal antiestrogen tamoxifen, were introduced by a thioether link on two types of nuclei (triphenylethane or estradiol). The new thioether derivatives were tested to assess their relative binding affinity for the estrogen receptor and their estrogenic or antiestrogenic activity in the ZR-75-1 (ER+) cell line. The results indicate that of the three types of compounds studied, only the nonsteroidal derivatives with an alkylamide side chain possess antiestrogenic activity. In the steroidal series, displacement of the alkylamide side chain from the 7 to the 6 position produced compounds with chemical characteristics similar to ICI 164384 or EM-139 but without antiestrogenic activity. In the nonsteroidal series of compounds with an aryl side chain, compounds with estrogenic activity were obtained. One compound, a nonsteroidal derivative with a methyl butyl alkylamide side chain 20, possesses a relative binding affinity for the estrogen receptor identical to EM-139 (1.1 and 1.2%, respectively) and a relatively good antiestrogenic activity that is 10-fold lower than EM-139 (IC50 values of 250 and 25 nM, respectively). This nonsteroidal thioether with an alkylamide side chain is free of estrogenic activity. PMID- 7779760 TI - Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats. AB - The effect of the synthetic antiprogestin RU486 on luteal function in late pregnant rats was studied by evaluating the activities of the enzymes 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). RU486 (2 mg/kg) administered to rats on day 18 of pregnancy at 10.00 h induced preterm delivery 26.4 +/- 0.35 h (n = 8) after treatment. Luteal 3 beta-HSD activity increased 24 and 34 h after RU486 injection, but a significant and progressive decrease started at 48 h with the maximal reduction 72 h after RU486 treatment, when compared with controls. Serum progesterone concentration decreased at the time of 3 beta-HSD activity reduction. Interestingly, 20 alpha-HSD activity started to increase 58 h after RU486 injection. The administration of the cyclooxygenase inhibitor, diclofenac (1.3 mg/kg), on days 17-19 of pregnancy to RU486-treated rats, delayed abortion and the duration of delivery, and prevented the decrease in 3 beta-HSD and the increase in 20 alpha-HSD activities observed 58 h after antiprogesterone treatment. RU486 administered intrabursally (1 microgram per ovary) on day 20 (14.00-15.00 h) increased 3 beta-HSD and decreased 20 alpha-HSD luteal activities at 18.00 h on day 21 of pregnancy, without modifying serum progesterone concentration, when compared with normal pregnant rats. In conclusion, the luteolytic process after preterm delivery induced by RU486 administration in late pregnant rats is characterized by a decrease in luteal 3 beta-HSD activity and circulating progesterone, which may trigger the increase in luteal 20 alpha-HSD activity. Prostaglandins seems to be involved in the increase of 20 alpha-HSD activity and therefore, in the demise of corpora lutea. PMID- 7779762 TI - Aldosterone synthase activity in the Y-1 adrenal cell line. AB - The Y-1 adrenal cell line was shown to produce 20 alpha-dihydroaldosterone from deoxycorticosterone. This compound was identified by GC-MS by comparison with the previously synthesized reference compound. Two other 18-hydroxylated metabolites were identified as 11 beta,18-dihydroxy-20 alpha-dihydroprogesterone from endogenous cholesterol and 18-hydroxy-20 alpha-dihydro-11-dehydrocorticosterone from DOC. The conditions necessary for the synthesis of these compounds are culturing in 20% serum-supplemented medium and repeated incubations with the substrate. The production of 11 beta-hydroxylated steroids and that of 18 oxygenated steroids is stimulated differently by ACTH and angiotensin II suggesting the expression of two different enzymes, cytochrome P-450(11)beta and cytochrome P-450aldo. The Y-1 cell line can secrete either 11 beta-hydroxylated steroids characteristic of the glucocorticoid pathway or 18-oxygenated steroids characteristic of the mineralocorticoid pathway, which in vivo are generally produced in two different zones of the adrenal cortex. This cell line should be an interesting model for the study of the molecular mechanisms regulating the expression of these two enzymes involved in the final steps of the steroidogenic pathways. PMID- 7779761 TI - Sex hormone changes induced by the parasite lead to feminization of the male host in murine Taenia crassiceps cysticercosis. AB - Female mice are more susceptible to Taenia crassiceps (TC) infection than males. However, after a month parasite load increases massively in both genders reaching thousands of parasites per host. The possibility of hormonal changes in the infected mice was envisaged. Sex hormones levels were assayed after different periods of infection, the parasites present in the peritoneal cavity were collected and gonads, uterus and seminal vesicles were weighed. In male mice, serum estradiol increased to levels 200 times their normal values whilst those of testosterone decreased 90% relative to controls. The weight of seminal vesicles was significantly diminished. Infected female mice also showed a slight increase in estrogen blood levels after 8 weeks of infection and the weight of the uterus was significantly increased relative to controls. Serum estradiol and testosterone were almost undetectable after gonadectomy. Cytokines such as IL-6 are capable of stimulating aromatase activity and we found that splenocytes from infected mice produced amounts of IL-6 higher than control as measured by ELISA. In conclusion T. crassiceps infection triggers a feminization process in the infected hosts. The gonads are required for the parasite to induce higher estrogen synthesis. IL-6 could be involved in the immunoendocrine mechanism used by the parasite to maintain a highly permissive environment for its rapid growth. PMID- 7779763 TI - 31P NMR study of phosphorus containing metabolites in the uterus of hamster: changes during the estrous cycle and the effect of hormonal manipulation. AB - Changes in the concentrations of phosphorus containing metabolites were monitored by 31P NMR in the uteri of hamsters during the estrous cycle. Concentrations of phosphocreatine (PCr) and ATP were significantly increased in estrus animals compared to diestrus animals. Concentrations of these metabolites were also increased in immature female hamsters and ovariectomized (OVX) adult hamsters treated with estradiol indicating that estradiol was responsible for this effect. However, the steroid hormones progesterone and testosterone did not increase the concentrations of the phosphorus containing metabolites. Further, immature female hamsters also following treatment with estradiol showed an initial decline in phosphomonoester (PME), PCr, ATP and inorganic phosphate but by 24 h of treatment the concentrations returned to control levels. The NMR study also revealed that the intracellular pH of the hamster uterus was around 7.4 all through the estrous cycle. PMID- 7779764 TI - Effect of PCBs on androgen production by suspension of adult rat Leydig cells in vitro. AB - The effects of PCBs (mixture of 2, 3, 4, 5-tetra; 2, 2', 4, 5, 5'-penta; 2, 2', 3, 3', 6, 6'-hexa and 2, 2', 3, 3', 4, 4', 5, 5'-octa congeners) on androgen production were investigated by suspension of Leydig cells from adult rat testis. hCG-stimulated androgen production was significantly inhibited by PCBs while progesterone level was not affected. Progesterone supported testosterone production was also decreased by PCBs, while conversion of androstenedione to testosterone was unchanged. These results suggest that the activity of microsomal enzyme C21 side-chain cleavage P450 was decreased by PCB treatment of Leydig cells in vitro. PMID- 7779765 TI - Therapist contributions to psychotherapeutic assimilation: an alternative to the drug metaphor. AB - A psychotherapist's verbal interventions may be understood as promoting a client's eventual improvement by facilitating developmental change processes within the client. This approach is an alternative to the traditional search for statistical links between aggregates of therapist interventions and global outcome measures. Our approach employs models of clients' assimilation of problematic experiences within problem domains and therapists' implementation of theoretically specified aims. In an empirical illustration, one client's change within a particular problem domain and its links with therapist interventions were assessed qualitatively across the course of brief psychodynamic interpersonal treatment. PMID- 7779768 TI - Psychopathology and personal agency: modernity, culture change and eating disorders in south Asian societies. AB - The cultural contribution to psychopathology may become more salient in situations of social change, but it remains difficult to distinguish individual agency among wider social and economic transitions, such as 'modernization' or simply 'culture change', which carry the potential for recourse to new patterns. Eating disorders, a biosocial pattern once identified exclusively with European societies, do occur among South Asian women including those living in the West. This seems not just a simple appropriation of contemporary Western ideals of female morphology--the 'fear of fatness'-but a reassertion of an instrumental strategy of self-renunciation in situations of experienced constraint. PMID- 7779767 TI - Post-adoption incest and phenotypic matching: experience, personal meanings and biosocial implications. AB - Recent changes in British law have enabled adults who were adopted when young to trace their biological relatives. The reported frequency of incestuous sentiments and relationships in these reunions, together with the individual experiences and the meanings which are attached to them, challenge fundamental assumptions of both Westermarck's and Freud's theories. Post-adoption incest is characterized experientially by a romantic search for attachment followed by a recognition of oneself in the other. The question of incest has been fundamental to biosocial theories of individual and cultural development. Some revisions are proposed, principally that adult sexual interests remain constrained both by early attachments and later phenotypic matching, reinforced by personal contingencies and cultural rules. PMID- 7779766 TI - Pornography and the paedophile: is it criminogenic? AB - There are few case-study-based reports of the role of pornography in the lives of sex offenders in contrast with numerous studies of a survey and statistical nature. Very little is known about the ways in which offenders process pornographic and other erotic materials as part of their offending patterns. The research reported in this study was based on case studies of fixated paedophiles in a private clinic for sex offenders. The men were interviewed about a range of matters including their offending, their psychosexual histories, pornography, fantasy, and sexual abuse in childhood. Commercial pornography was rarely a significant aspect of their use of erotica although some experience of such materials was typical of the men. Most common was 'soft-core' heterosexually oriented pornography. Explicit child pornography was uncommon. However, offenders also generated their own 'erotic' materials from relatively innocuous sources such as television advertisements, clothing catalogues featuring children modelling underwear, and similar sources. In no case did exposure to pornography precede offending-related behaviour in childhood. All of the offenders had experienced childhood sexual abuse by adults or older peers. The relationship of these findings to previous research and implications for legislation are noted. PMID- 7779769 TI - The ideas and experiences of pregnancy and childbirth of Asian and non-Asian women in east London. AB - This study examined differences between the ideas and experiences of pregnancy and childbirth of Asian and non-Asian women giving birth in East London, and sources of variability in Asian women's accounts. In line with the findings of previous research, Asian women's ideas about diet in pregnancy, the gender of their children and postnatal care (e.g. the need for rest and recovery, and restrictions on their activities) were influenced by cultural beliefs and practices. However, in other ways Asian women demonstrated a strong commitment to Western maternity care. In contrast to some other studies Asian women wanted their husbands or partners present at delivery, indicating the extent to which traditional ideas are being modified. Qualitative analysis of Asian women's fuller accounts indicated that women subscribed to traditional practice as well as Western maternity care. Acculturation or familiarity with Western ideas about maternity care was associated with variability in Asian women's ideas and experiences, in line with previous research. However, in spite of frequent assumptions about its significance, religion was not associated with variability in Asian women's ideas and experiences. Parity, however, was a major variable, for Asian and for non-Asian women, suggesting that the first birth has different significance for parents than subsequent births. The implications for the provision of maternity care are discussed, especially the need to go beyond stereotypical views based on women's ethnicity or religion to consider the beliefs and preferences of women as individuals and their personal circumstances. PMID- 7779770 TI - The process of coping with a gross anatomy exam during the first year of medical school. AB - A total of 42 freshman medical students were evaluated before a major exam, after the exam and before grades were announced and after grades were announced. They completed measures relating to mood, emotions, coping, social support and stakes. Significant time and academic performance differences were found in many domains. PMID- 7779772 TI - Phase polymorphism, molecular interactions, and miscibility of binary mixtures of dimyristoyl-N-biotinylphosphatidylethanolamine with dimyristoylphosphatidylcholine. AB - The phase diagram of hydrated binary mixtures of dimyristoyl-N biotinylphosphatidylethanolamine with dimyristoylphosphatidylcholine in 1 M NaCl has been established by differential scanning calorimetry. Identification of the structures of the phases involved has been made by using X-ray diffraction, spin label ESR spectroscopy, and 31P NMR spectroscopy. On the composition axis, the phase diagram is divided into three regions corresponding to formation of compounds in the gel phase with biotinyl lipid to phosphatidylcholine stoichiometries of approximately 1:1 and 1:3 mol/mol. For the first two regions (up to 75 mol % phosphatidylcholine), the lipids in the gel phase have interdigitated chains (L beta i), whereas in the third region the gel phase is not interdigitated (L beta' or L beta). For the first region (up to 50 mol % phosphatidylcholine), the fluid phase is of the novel isotropic type (IMI) composed of aggregated normal micelles that is characteristic of shorter chainlength biotinylated lipids [Swamy, M.J., Wurz, U., & Marsh, D. (1993) Biochemistry 32, 9960-9967], whereas for the other two regions a normal fluid lamellar (L alpha) phase obtains. The equimolar mixture, which lies at a stoichiometric phase boundary, melts isothermally and then undergoes a transition from the isotropic IMI structure to the lamellar L alpha structure with increasing temperature in the fluid phase. PMID- 7779771 TI - Immobilized proteoliposome affinity chromatography for quantitative analysis of specific interactions between solutes and membrane proteins. Interaction of cytochalasin B and D-glucose with the glucose transporter Glut1. AB - An affinity gel bed was prepared by reconstitution of a transmembrane protein, the human red cell glucose transporter (Glut1), followed by steric immobilization of the proteoliposomes in small and rigid gel beads by freeze-thawing. The specific interactions between the reconstituted Glut1, the transport inhibitor cytochalasin B (CB), and the transported solute D-glucose were analyzed by isocratic chromatography of CB on the Glut1-proteoliposome gel bed. Specific retardation of CB which decreased upon inclusion of the competitor D-glucose in the eluent was observed on-line. The equilibrium constants for CB and D-glucose interaction with Glut1 (Kd 1.5 x 10(-7) M and 67 mM, respectively) obtained by use of equations derived for the affinity chromatographic analysis were consistent with values obtained by others by conventional methods. Effects of liposome composition, pH, and time on the CB binding activity of Glut1 were studied. Reconstitution of a membrane protein into a lipid environment and steric immobilization of the proteoliposomes favor retention of the protein activity. Immobilized proteoliposome affinity chromatography (IPAC) is a novel, powerful method for analysis of interactions between membrane proteins and solutes. PMID- 7779773 TI - Purification and reconstitution of murine mitochondrial glycerol-3-phosphate acyltransferase. Functional expression in baculovirus-infected insect cells. AB - Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial step in glycerolipid biosynthesis. We recently cloned a cDNA to a 6.8-kb mRNA, a message that can be induced dramatically by feeding a high-carbohydrate diet [Paulauskis & Sul (1988) J. Biol. Chem. 263, 7049-7054; Shin et al. (1991) J. Biol. Chem. 266, 23834-23839], and identified the open reading frame, p90, as mitochondrial GPAT [Yet et al. (1993) Biochemistry 32, 9486-9491]. To initiate characterization of mitochondrial GPAT, we purified and reconstituted the GPAT activity using phospholipids after expressing functional enzyme in Sf9 insect cells. Infection with recombinant virus containing p90 sequence resulted in high levels of GPAT expression in mitochondria, compared to noninfected cells or cells infected with the reverse orientation insertion baculovirus. There was a dramatic increase in N ethylmaleimide-resistant mitochondrial GPAT activity. The GPAT protein was not detectable by Western blot in noninfected Sf9 cells or in cells infected with the GPAT sequence in the reverse orientation. However, in cells infected with GPAT in the correct orientation, there was a dramatic increase in the GPAT protein that was readily detectable by Coomassie staining both in total extracts and in the mitochondrial fraction. To ease the purification, we next expressed GPAT as a polyhistidine fusion protein in insect cells. The polyhistidine tag did not interfere with targeting to mitochondria or with the catalytic activity of GPAT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779774 TI - Structure of the catalytic region of human complement protease C1s: study by chemical cross-linking and three-dimensional homology modeling. AB - C1s is a multidomain serine protease that is responsible for the enzymatic activity of C1, the first component of the classical pathway of complement. Its catalytic region (gamma-B) comprises two contiguous complement control protein (CCP) modules, IV and V (about 60 residues each), a 15-residue intermediary segment, and the B chain (251 residues), which is the serine protease domain. With a view to identify domain-domain interactions within this region, the gamma B fragment of C1s, obtained by limited proteolysis with plasmin, was chemically cross-linked with the water-soluble carbodiimide 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide; then cross-linked peptides were isolated after CNBr cleavage and thermolytic digestion. N-Terminal sequence and mass spectrometry analyses allowed us to identify two cross-links between Lys 405 of module V and Glu 672 of the B chain and between Glu 418 of the intermediary segment and Lys 608 of the B chain. Three-dimensional modeling of the CCP modules IV and V and of the catalytic B chain was also carried out on the basis of their respective homology with the 16th and 5th CCP modules of complement factor H and type I serine proteases. The information provided by both the chemical cross linking studies and the homology modeling enabled us to construct a three dimensional model for the assembly of the C-terminal part of the gamma-B region, comprising module V, the intermediary segment, and the B chain. This model shows that module V interacts with the serine protease B chain on the side opposite to both the activation site and the catalytic site. Functional implications of this interaction are discussed in terms of the possible role of module V in the specific recognition and positioning of C4, one of the two substrates of C1s. PMID- 7779775 TI - Phospholipase A2 engineering. Probing the structural and functional roles of N terminal residues with site-directed mutagenesis, X-ray, and NMR. AB - The N-terminal residues of phospholipase A2 (PLA2) are believed to be involved in the hydrogen-bonding network, the interfacial binding site, or the hydrophobic channel. Site-directed mutants of bovine pancreatic PLA2 with substitutions at positions 2, 3, 4, 5, 6, and 9 were constructed to test the roles of these residues in the structure and function of PLA2. Nonconservative mutations of Phe 5 and Ile-9, which are located inside the hydrophobic channel, led to significant perturbations in the conformation and conformational stability. Kinetic studies also indicated that mutations at Ile-9 and Phe-5 caused significant decreases in the rate of hydrolysis toward micellar and vesicle substrates. Scooting mode kinetic analysis showed that the binding step of the mutant enzymes to the DC14PM (1,2-dimyristoyl-sn-glycero-3-phosphomethanol) vesicle interface is not significantly affected and that the perturbations in catalysis occur mainly in kcat at the interface. The results taken together suggest that the residues Ile-9 and Phe-5 are important for both structure and catalysis. The mutant W3A (Trp-3 to Ala) also showed decreased rates of hydrolysis but to a lesser extent than Ile 9 and Phe-5 mutants. In addition, the binding affinity of W3A to the surface of the vesicles (i.e., the E to E* step) has been perturbed to the extent that hopping between anionic vesicles has been observed. On the other hand, the mutants of Gln-4 and Asn-6, which are located at or near the surface, displayed structural and kinetic properties similar to those of the wild-type PLA2 with the exception of the highly hydrophilic lysine mutant. The X-ray structure of the Q4E mutant indicates that the overall structure, the catalytic triad, and the link between residue 4 and Asp-99 via hydrogen bonding through Ala-1 and the structural water remain the same as in the WT. Substitutions for Leu at position 2 showed an acyl chain length discrimination toward different substrates, which may reflect the contacting position(s) of the substrate acyl chain with Leu-2. PMID- 7779776 TI - Electron tunneling and ab initio calculations related to the one-electron oxidation of NAD(P)H bound to catalase. AB - Models for NAD(P)H le- oxidation in bovine catalase were studied using Hartree Fock ab initio calculations, along with information taken from the published X ray structure of the enzyme. Geometries and energies of ground states and transition states were calculated at the 6-31G* level for N-methyl-1,4 dihydropyridine and N-methyl-1,4-dihydronicotinamide undergoing the pathway (i) le- oxidation to yield the radical cation, (ii) general-base-catalyzed (hydroxide and/or imidazole) deprotonation of the radical cation to yield the neutral radical, and (iii) le- oxidation of the neutral radical to the N-methylpyridinium or N-methylnicotinamide cation. Barrier heights for deprotonation of the radical cation intermediates were calculated to be 7-11 kcal/mol. Kinetic isotope effects were calculated for general-base-catalyzed deprotonation of the N-methyl-1,4 dihydropyridine radical cation and the 4,4-dideuterio species and found to be kH/kD2 = 5.38 (hydroxide) or 3.64 (imidazole), in qualitative agreement with published experimental isotope effects for the analogous deprotonation of N methyl-1,10-dihydroacridan or the N-methyl-1,10-dideuterioacridan radical cation. In the calculated transition state for imidazole deprotonation of the N-methyl 1,4-dihydronicotinamide radical cation, an unusual short contact was calculated and interpreted as a hydrogen bond (2.35 A) between the amide oxygen and the hydrogen attached to C2 of imidazole. Similar hydrogen bonds were also observed and calculated at the 3-21G and 6-31G* levels between His234 of catalase and the amide oxygen of bound NAD(P)H and complexes of N,N'-dimethyl-1,4 dihydronicotinamide or cis-N-methylformamide with N-methylimidazole. Comparison of these results to the X-ray structure of bovine catalase allows for further interpretation of the possible roles of the imidazole bases His234 and His304 and the hydrogen-bonded contacts in the NAD(P)H binding site. Electron tunneling pathways between NAD(P)H and the iron protoporphyrin IX (PP-IX) axial tyrosinate ligand Tyr357 in molecular dynamics and X-ray crystal structures of bovine catalase were calculated using PATHWAYS II (version 2.01). The pathways which were calculated included those involving the amino acid residue Tyr214, which is near the NAD(P)H binding site. Coupling involving Tyr357 was not particularly efficient; however, strong coupling between Tyr214 and iron-protoporphyrin IX was observed. These pathways may be important if electron transfer is stepwise; i.e., Tyr214 oxidized first, followed by NAD(P)H. PMID- 7779777 TI - Functional role of arginine-11 in the N-terminal helix of skeletal troponin C: combined mutagenesis and molecular dynamics investigation. AB - The two main structural differences between calmodulin (CaM) and skeletal troponin C (sTnC) are the absence in CaM of (i) the short N-terminal helix in TnC and (ii) the triplet KGK (residues 91-93; numbering according to chicken sTnC). It was recently shown that deletion of both structural groups from sTnC imparted to the resulting construct the CaM-like ability to activate phosphodiesterase (PDE) and to regulate force development in smooth muscle. To continue probing of the structural basis of the differential behavior of sTnC and CaM, residue Arg-11 in rabbit sTnC was mutated to Ala because the interactions of Arg-11 with distal residues in the N-terminal domain seem to link the N-terminal helix to the rest of the structure. The mutant exhibits CaM-like function in its ability to activate PDE (about 50% of CaM at 5 microM concentration). If, in addition, the KGK triplet is also deleted, PDE activation increases to about 80%. Both constructs retain their TnC function to nearly 100%. To explore the mechanistic basis of this remarkable observation, computational simulations of the molecular dynamics (MD) were carried out for both wild-type 4Ca2+.sTnC and the 4Ca2+.R11A mutant, and the results were compared to those from earlier simulations of 4Ca2+.CaM. Two types of structural changes observed from such simulations of the molecular dynamics of CaM had been considered to have a functional role: (i) a compaction to a more globular form and (ii) a reorientation of the Ca-binding domains around the central tether helix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779778 TI - Calcium-induced dimerization of troponin C: mode of interaction and use of trifluoroethanol as a denaturant of quaternary structure. AB - Protein aggregation can be a problem, especially as a large number of proteins become available for structural studies at fairly high concentrations using solution techniques such as NMR spectroscopy. The muscle regulatory protein troponin C (TnC) undergoes a calcium-induced dimerization at neutral pH with a dissociation constant for the dimerization of 0.4 mM at 20 degrees C. The present study indicates that the mode of dimerization involves the N-domain of one monomer interacting with the N-domain of another monomer. Addition of the solvent trifluoroethanol (TFE) to a concentration of 15%, v/v, results in a 10-fold increase in the dimer dissociation constant of calcium-saturated TnC (4 mM at 20 degrees C), making TnC predominantly a monomer for spectroscopic studies. Further, TFE, at the concentrations used herein, acts to perturb the quaternary structure of TnC without adversely affecting the secondary or tertiary structure as evidenced by minimal changes to its CD spectra and 1H, 13C, and 15N NMR chemical shifts. PMID- 7779779 TI - Neurofilament-associated protein phosphatase 2A: its possible role in preserving neurofilaments in filamentous states. AB - Neurofilament phosphatase (NF-phosphatase) activity, which dephosphorylates NF proteins phosphorylated by cyclic AMP-dependent protein kinase (A-kinase), was detected in NF fractions prepared from bovine spinal cords. This phosphatase was suggested to be associated with NFs by gel filtration and sedimentation analysis and was further demonstrated by dephosphorylation-dependent binding assay of NFs to microtubules. The NF-associated NF-phosphatase was identified as a type of protein phosphatase 2A (PP2A) by (i) its complete inhibition with 100 nM okadaic acid, at which concentration the purified type 1 protein phosphatase (PP1) was inhibited only 25%; (ii) the absence of effect of inhibitor-2, a specific inhibitor of PP1, on the NF-phosphatase activity; and (iii) the detection of 38 kDa catalytic and 65-kDa regulatory subunits of PP2A by immunoblotting. The NF associated PP2A was partially solubilized from NFs by a high concentration of MgSO4, and the solubilized PP2A was suggested by gel filtration to be a dimeric holoenzyme consisting of a 38-kDa catalytic and a 65-kDa regulatory subunit. Phosphorylated NF-L, which is assembly incompetent, was induced to assemble into filaments by dephosphorylation with PP2A. These results suggest a role of NF associated PP2A in preserving filamentous forms of NF in neurons. PMID- 7779781 TI - Insect immunity. The inducible antibacterial peptide diptericin carries two O glycans necessary for biological activity. AB - A bacterial challenge of larvae of the dipteran insect Phormia terranovae induces the rapid synthesis of diptericin, an antibacterial polypeptide, previously characterized at the amino acid level and indirectly by cDNA cloning studies. This 82-residue polypeptide consists of an N-terminal proline-rich domain and a central and C-terminal glycine-rich domain. Using liquid chromatography coupled to electrospray ionization-mass spectrometry, we demonstrate here that this molecule is more complex than anticipated and carries two O-substitutions on threonine residues, one in the proline-rich domain (residue 10) and one in the glycine-rich domain (residue 54). These substitutions consist of identical trisaccharides: glucose-->galactose-->N-acetylgalactosamine-->(threonine). Treatment of diptericin with O-glycosidase, which selectively removes the substitutions without altering the polypeptide proper, abolishes the antibacterial activity, indicating that this posttranslational modification is essential for biological activity of the polypeptide. We also show that diptericin is posttranslationally modified by a C-terminal amidation. PMID- 7779780 TI - Characterization of the N-terminal and C-terminal domains of human apolipoprotein(a): relevance to fibrin binding. AB - The structural domains of human apolipoprotein(a) (apo(a)) in the lipoprotein(a) (Lp(a)) particle have been recently investigated by limited proteolysis [Huby, T., Doucet, C., Dieplinger, H., Chapman, J., & Thillet, J. (1994) Biochemistry 33, 3335-3341]. We have shown that apo(a) can be cleaved into two structural domains: one was of constant size (170 kDa) and corresponded to the C-terminal (Cter) domain of apo(a). This domain was linked by a disulfide bond to apo B100. By contrast, the N-terminal (Nter) domain, whose size varied according to the digested apo(a) isoform, was not linked to apo B100. We now describe the purification of these apo(a) domains and their interaction with fibrin surfaces in an in vitro binding assay. The Nter domain of apo(a) was purified as a soluble protein in a two-step procedure which involved sequential use of a heparin Sepharose column and a lysine-Sepharose column. The Cter domain of apo(a), which remained in disulfide linkage with apo B100 of Lp(a), was isolated as a lipoprotein particle by a combination of chromatographic steps on heparin Sepharose and Q-Sepharose columns. This particle, termed "mini-Lp(a)", appeared homogeneous in nondenaturing polyacrylamide gels and exhibited a particle size (285 A) which was intermediate between that of Lp(a) (300 A) and LDL (265 A). The cleavage site between the respective apo(a) domains was determined by N-terminal sequencing of the purified Cter domain. Such cleavage occurred between residues 3532 and 3533, which are located in the interkringle region between apo(a) kringles 4(4) and 4(5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779782 TI - Conformation of two peptides corresponding to human apolipoprotein C-I residues 7 24 and 35-53 in the presence of sodium dodecyl sulfate by CD and NMR spectroscopy. AB - Peptides corresponding to the proposed lipid-binding domains of human apolipoprotein C-I, residues 7-24 (ALDKLKEFGNTLEDKARE) and 35-53 (SAKMREWFSETFQKVKEKL), were studied by CD and two-dimensional 1H NMR spectroscopy. Sodium dodecyl sulfate (SDS) was used to model the lipoprotein environment. Analysis of the CD data shows that both peptides lack well-defined structure in aqueous solution but adopt helical, ordered structures upon the addition of SDS. The helical nature of the peptides in the presence of SDS was confirmed by H alpha secondary shifts. A total of 199 (apoC-I(7-24)) and 266 (apoC-I(35-53)) distance restraints were used in distance geometry and simulated annealing calculations to generate average structures for both peptides in aqueous solutions containing SDS. The backbone (N, C alpha, C = O) RMSD from the average structure of an ensemble of 20 structures was 0.73 +/- 0.22 and 0.48 +/- 0.14 A for apoC-I(7-24) and apoC-I(35-53), respectively. In the presence of SDS, the distance geometry and simulated annealing calculations show that both peptides adopt well-defined amphipathic helices with distinct hydrophobic and hydrophilic faces. The calculated structures are discussed relative to predicted structures. Comparing our CD and NMR results for the apoC-I fragments in SDS with CD results of others obtained in the presence of dimyristoylphosphatidylcholine indicates that SDS may be a better model of the lipoprotein environment. PMID- 7779784 TI - The conformations of a functional spin-labeled derivative of gastric H/K-ATPase investigated by EPR spectroscopy. AB - A spin-labeled derivative of porcine gastric H/K-ATPase with high ATP hydrolyzing activity (77 mumol of Pi/(mg.h)) has been prepared. Over 65% of initial ATPase activity (115 mumol of Pi/(mg.h)) was preserved after complete reaction of the enzyme with the lysine reactive nitroxide spin-labeled TEMPO isothiocyanate (TITC). In contrast, rapid and complete loss of ATPase activity occurred after reaction of the enzyme with the lysine directed fluorescent probe FITC. Conventional EPR spectra of TITC labeled H/K-ATPase reflected mainly the slow rotational diffusion of the enzyme in the membrane. An upper limit enzyme intramembranous radius of 108 A was calculated on the basis of rotational correlation times estimated from saturation transfer (ST) EPR spectral lineshapes. Conventional EPR spectra exhibited two major components corresponding to at least two populations of strongly constrained spin-labels. Difference spectroscopy revealed that the proportion of these two components changed markedly with temperature. Moreover, the proportion of the components was sensitive to the presence of the activating ionic ligands Mg2+ and ATP, which induce enzyme conformational transitions, and to the reversible inhibitor SCH 28080, which binds to the K+ sensitive form of the enzyme. These findings show that EPR spectroscopy is able to report functionally coupled conformational changes of gastric H/K-ATPase and imply that the spin-labels are attached to lysines within functionally important regions of the enzyme. PMID- 7779783 TI - Site-directed mutagenesis of putative GTP-binding sites of yeast beta-tubulin: evidence that alpha-, beta-, and gamma-tubulins are atypical GTPases. AB - The exchangeable GTP-binding site on beta-tubulin has been extensively studied, but the primary sequence elements which form the binding site on beta-tubulin remain unknown. We have used site-directed mutagenesis of the single beta-tubulin gene of Saccharomyces cerevisiae to test a model for the GTP-binding site on beta tubulin, which was based on sequence comparisons with members of the GTPase superfamily [Sternlicht, H., Yaffe, M.B., & Farr, G. W. (1987) FEBS Lett. 214, 226-235]. We analyzed the effects of D295N, N298K, and N298Q mutations in a proposed base-binding motif, 295DAKN298, on tubulin-GTP binding and on nucleotide binding specificity. We also examined the effects of a D203S mutation in a putative phosphate-binding region, 203DNEA206, on nucleotide binding affinity, on the assembly-dependent tubulin GTPase activity in vitro, and on the dynamic properties of individual "mutant" microtubules in vitro. The effects of the mutations on cell phenotype and on microtubule polymerization in cells were also measured. The results do not support the proposal that the 203DNEA206 and 295DAKN298 [corrected] motifs are cognate to motifs found in GTPase superfamily members. Instead, the data argue that the primary sequence elements of beta tubulins that interact with bound nucleotide, and presumably also those of the alpha- and gamma-tubulin family members, are different from those of "typical" GTPase superfamily members, such as p21ras. The GTPase superfamily should thus be broadened to include not just the typical GTPases that show strong conservation of primary sequence consensus motifs (GxxxxGK, T, DxxG, NKxD) [corrected] but also "atypical" GTPases, exemplified by the tubulins and other recently identified GTPases, that do not show the consensus motifs of typical GTPases and which also show no obvious primary sequence relationships between themselves. The tubulins and other atypical GTPases thus appear to represent convergent solutions to the GTP-binding and hydrolysis problem. PMID- 7779785 TI - Secretion of yeast aspartic protease 3 is regulated by its carboxy-terminal tail: characterization of secreted YAP3p. AB - Yeast aspartic protease 3 (YAP3p), a basic-residue specific proprotein processing enzyme, was shown to be a membrane-associated protease. The membrane association of YAP3p was demonstrated to be through a glycophosphatidylinositol anchor situated in the carboxy terminus of the enzyme. Carboxy-terminal truncation of YAP3p by 37 amino acids resulted in secretion of YAP3p into the growth medium. Western blot analysis after sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed two secreted forms of YAP3p with apparent molecular masses of approximately 180 and approximately 90 kDa. YAP3p has an isoelectric point of approximately 4.5 as determined by isoelectric focusing gel electrophoresis. Treatment of YAP3p with endoglycosidase H reduced the size of both forms of the protein to approximately 65 kDa, consistent with the presence of 10 potential N linked glycosylation sites in the deduced amino acid sequence of this protein. Removal of the N-linked sugars did not affect the enzymatic activity of YAP3p. Analysis of the effect of temperature on the stability and the rate of enzymatic activity of YAP3p showed that the enzyme retained 100% of its activity when incubated for 1 h at 37 degrees C, while incubation at 50 degrees C for 1 h resulted in approximately 80% loss of activity. The dependence of activity on temperature demonstrated a calculated Q10 of 1.95. PMID- 7779786 TI - Incision at diaminopurine: thymine base pairs but not at guanine:O4-methylthymine base pairs in DNA by extracts of human cells. AB - Cell-free extract from the A1235 human malignant glioma cell line was employed to study the possibility of incision at 2,6-diaminopurine:T (DiAP:T), 2-amino-6 methylaminopurine:T (AMAP:T), and G:O4-methylthymine (G:m4T) mismatches, each placed in a 45 bp DNA at a defined site. The incision of a 45 bp DNA containing a G:T mispair at the same site was followed to determine the relationship between base pair structure and repair activity (ies) in the extract. The cell-free extract incised DNAs containing DiAP:T, AMAP:T, and G:T pairs similarly. Reminiscent of the known pattern of incision at G:T mismatches, products from each substrate were consistent with two incisions, one immediately 5' and one immediately 3' to the mismatched T, and only in the strand containing the mismatched T. While DNA with an O6-methylguanine:T (m6G:T) pair was also incised, DNA containing the G:m4T pair was not, but was rendered inciseable by pretreatment with O6-methylguanine-DNA methyltransferase. Incision of DiAP:T containing DNA by the extract was less in the presence of unlabeled DNA containing G:T mispairs than in the presence of A:T- or G:A-containing DNA or in the absence of competing DNA. We suggest that the mechanism operating on DiAP:T and/or AMAP:T pairs may be the same as the human G:T repair pathway, possibly initiated by the action of a glycosylase as described by Wiebauer and Jiricny [Wiebauer, K., & Jiricny, J. (1989) Nature 339, 234-236; Wiebauer, K., & Jiricny, J. (1990) Proc. Natl. Acad. Sci, U.S.A. 87, 5842-5845].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779787 TI - Photoincorporation of 4,4'-bis(1-anilino-8-naphthalenesulfonic acid) into the apical domain of GroEL: specific information from a nonspecific probe. AB - The use of noncovalent hydrophobic probes such as bis-ANS has become increasingly popular in gaining structural information about protein structure and conformation. While these probes have provided rich information about protein conformation, specific information has been limited. In this report, we extend the usefulness of the probe bis-ANS by showing that it can be covalently photoincorporated into various proteins. Using the chaperonin GroEL, we have shown that it is possible to locate important hydrophobic surfaces through photoincorporation and peptide sequencing. It has been proposed that hydrophobic surfaces on the chaperonin may be responsible for the binding of unfolded polypeptides. We show here that photoincorporation of bis-ANS is able to locate a distinct hydrophobic surface on GroEL. Incorporation of the bis-ANS occurs within a 45 residue fragment of the monomer near the middle of the primary sequence. Interestingly, photoincorporation occurs within this fragment in both tetradecamers and assembly-competent monomers. From the three-dimensional structure of GroEL, this region maps to the apical domain (residues 191-376), which has been implicated in polypeptide binding [Fenton, W. A., Kashi, Y., Furtak, K., & Horwich, A. L. (1994) Nature 371, 614-619]. In addition, the fluorescent properties of the probe are retained including the excitation and emission maxima and the sensitivity to the polarity of its environment. These results suggest that photoincorporated bis-ANS may be a useful probe for protein structure and dynamics. PMID- 7779788 TI - Characterization of tyrocidine synthetase 1 (TY1): requirement of posttranslational modification for peptide biosynthesis. AB - Tyrocidine synthetase 1 (TY1), produced by Bacillus brevis ATCC 8185, consists of a single multifunctional polypeptide chain catalyzing the activation, thioesterification, and epimerization of phenylalanine. Because we were concerned about possible posttranslational issues, a comparative study between the wild type isolate and the in Escherichia coli overexpressed protein was performed. Analysis by matrix assisted laser desorption mass spectrometry (MALDI) provided a molecular mass of 122,516 +/- 120 Da for the recombinant protein, which is in agreement with the value of 122,590 Da calculated from the gene sequence. MALDI analysis of the tryptic fragments revealed that in the recombinant TY1 the putative 4'-phosphopantetheine binding site (562Ser) is not modified by the cofactor. The substrate specificity profiles of the amino acid dependent ATP[32P]PPi exchange reactions were identical, including activation of L phenylserine, L-tyrosine, and L-methionine. However, the rates of the reverse adenylation reaction for the recombinant protein were only 22% relative to those of the wild-type enzyme. The aminoacylation levels of about 60% for TY1 from Bacillus brevis reduced to 1.4% in the overexpressed protein. A similar distribution of the D- and the L-isomer was detected at the thioester attachment site. The pI values of the wild-type and expressed TY1 are 4.9 and 5.0, respectively. In conclusion, it could be established that apo- and holo-TY1 differ in their amino acid activating properties. Posttranslational modification by 4'-phosphopantetheine is an essential requirement for aminoacylation, epimerization, and thus the functioning of the multienzyme in peptide synthesis. PMID- 7779790 TI - Conversion of cytochrome f to a soluble form in vivo in Chlamydomonas reinhardtii. AB - We introduced a stop codon in place of the ATT codon encoding Ile283 (numbered from the Met initiation codon) in the petA gene from Chlamydomonas reinhardtii. The resulting protein was expected to be truncated on its carboxy-terminus end, lacking the last 35 amino acids. This region of the polypeptide sequence encompasses a hydrophobic stretch assumed to anchor the protein in the thylakoid membrane. Once introduced in whole cells of C. reinhardtii by chloroplast transformation, the modified petA gene expressed a truncated apoprotein which was efficiently converted to a truncated holocytochrome f. This protein accumulated in the lumen of the thylakoids in a soluble form. Thus the conversion of preapocytochrome f to holocytochrome f does not require an interaction with the membrane through its C-terminus anchor. We show that the rest of the cytochrome b6f complex failed to accumulate in the transformants, most probably because of a lack of interaction between soluble cytochrome f and the other cytochrome b6f subunits. However, soluble cytochrome f was still able to donate electrons to photosystem I, which is indicative of its ability to maintain interactions with plastocyanin. The control of the rate of synthesis of cytochrome f by the neighboring subunit, suIV (Kuras & Wollman (1994) EMBO J. 13, 1019-1027), was not observed with the truncated cytochrome f. This observation suggests that either the transmembrane anchor of cytochrome f contains a target for the regulation of cytochrome f translation by suIV or there is a transient form of membrane-bound cytochrome f which is highly sensitive to proteolysis at an early post translational stage. PMID- 7779789 TI - Characterization and sequential localization of the metal clusters in sea urchin metallothionein. AB - The mode of metal binding in sea urchin metallothionein (MT) was explored by electronic absorption, chiroptical, NMR, and mass spectroscopic methods. Recombinant sea urchin MT containing 7 equiv of the natural mixture of Cd isotopes was stripped of the metal by exposure to low pH and reconstituted with 113Cd (> 95% enriched). Comparison of the electronic spectroscopic and chiroptical features and the 113Cd NMR spectra of the reconstituted material with those of the native recombinant material indicated that the reconstituted material had regained the native conformation. The shoulder at 250 nm in the electronic absorption spectrum, the biphasic circular dichroism profile centered at 250 nm, and the chemical shift positions (605-695 ppm) of the seven 113Cd NMR resonances all strongly suggested that sea urchin MT like all other well characterized MTs contains clusters made up of tetrahedral Cd-thiolate units. The 113Cd chemical shift correlation spectrum of the reconstituted protein proved the existence of such metal clusters and allowed the unambiguous assignment of some of the metal connectivities. Homonuclear decoupling experiments in which Cd resonances were selectively saturated indicated moreover a partitioning of the metal complement into two separate clusters containing three and four Cd ions. The same proposition was supported by the selective reduction of three 113Cd resonances upon partial metal depletion following exposure of the protein to EDTA. Thus, the three-metal cluster is energetically less stable than the four metal cluster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779791 TI - Topographical organization of cytochrome b in the yeast mitochondrial membrane determined by fluorescence studies with N-cyclohexyl-N'-[4 (dimethylamino)naphthyl]carbodiimide. AB - In previous studies, we reported that dicyclohexylcarbodiimide (DCCD) inhibited proton translocation in the cytochrome bc1 complex from yeast mitochondria and was bound selectively to cytochrome b. Extensive trypsin digestion of [14C]DCCD labeled cytochrome b isolated from a cytochrome bc1 complex treated with DCCD yielded a single radiolabeled 7.0 kDa peptide with the N-terminus VTLWNVG, indicating that trypsin cleavage had occurred at arginines-110 and -178. This segment of cytochrome b contains one acidic residue, aspartate-160, localized in amphiphilic, non-membrane-spanning, helix cd. To explore the environment of amphiphilic helix cd, we employed a fluorescent derivative of DCCD, N-cyclohexyl N'-[4-(dimethylamino)naphthyl]carbodiimide (NCD-4). After incubation of NCD-4 with a cytochrome bc1 complex isolated from yeast mitochondria, a fluorescent compound was formed with a 340 nm excitation peak and a 441 nm emission peak. NCD 4 was selectively bound to cytochrome b and inhibited proton translocation with only a minimal inhibitory effect on electron transfer in the cytochrome bc1 complex reconstituted into proteoliposomes. Competition experiments and trypsin digestion of NCD-4-labeled cytochrome b indicated that NCD-4 and DCCD were bound to the same site on cytochrome b. The fluorescence of NCD-4 bound to the cytochrome bc1 complex was quenched equally by CAT-16, an amphiphilic spin-label that intercalates at the membrane surface, and 5-doxylstearic acid, a nitroxide derivative of stearic acid, and to a lesser extent by 7-doxylstearic and 12 doxylstearic acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779792 TI - Control of electron delivery to the oxygen reduction site of cytochrome c oxidase: a role for protons. AB - We have studied the reaction of oxidized "pulsed" cytochrome c oxidase with reduced cytochrome c and with ruthenium(II) hexaammine using stopped-flow mixing. The rate of reduction of Fea3 (the oxygen-binding heme) is not a linear function of the population of reduced Fea (the low-spin heme), as would be expected if electron transfer between these sites is rate-limiting. Instead, the rate can be increased significantly by increasing the driving force of the reductant (lowering of Eh) even after Fea is almost completely reduced. Reduction of Fea3 becomes slower as the pH is raised, and consumption of protons can be seen simultaneously with electron entry into Fea3. Both the reduction of Fea3 and the proton uptake are biphasic. To explain these findings, we propose a model in which (1) intramolecular heme-heme electron transfer is fast, and has an essentially constant rate; (2) when reduction begins, the midpoint potentials of Fea3 and CuB are initially low, and only a small fraction of these centers become reduced; and (3) this reduced population is then stabilized by the uptake of protons. Thus, net reduction of Fea3 and CuB is controlled by the amount of the low-potential population which becomes reduced together with the rate of proton uptake by this reduced low-potential species. Important consequences of this mechanism for the function of the enzyme and for the respiratory chain as a whole are discussed. PMID- 7779793 TI - Interaction of the 33-kDa extrinsic protein with photosystem II: identification of domains on the 33-kDa protein that are shielded from NHS-biotinylation by photosystem II. AB - The structural association of the spinach 33-kDa extrinsic protein of photosystem II with the membrane-bound components of the photosystem was investigated by labeling the 33-kDa extrinsic protein with the amino group-specific reagent N hydroxysuccinimidobiotin both on NaCl-washed photosystem II membranes and free in solution. After quenching of the labeling reagent and isolation of the biotinylated molecules, the biotinylation sites were identified by Staphylococcus V8 protease digestion and analysis of the resultant peptide fragment mixture by matrix-assisted laser desorption/ionization mass spectrometry. When the 33-kDa extrinsic protein was modified on PS II membranes, three domains were biotinylated: 14K, 41K-76K, and 190K-236K. When the 33-kDa extrinsic protein was modified in solution, four additional domains were biotinylated: 1E-4K, 20K, 101K 105K, and 159K-186K. These additional modified domains reside in portions of the 33-kDa protein that are not accessible to the bulk solvent when the protein is associated with PS II and may define regions of interaction with the photosystem. PMID- 7779794 TI - Trypsin treatment of reaction centers from Rhodobacter sphaeroides in the dark and under illumination: protein structural changes follow charge separation. AB - Reaction centers from Rhodobacter sphaeroides R-26 were treated with trypsin in the dark and during illumination (in the charge-separated state). Trypsination resulted in a time-dependent modification of the reaction centers, reflected in changes in the charge recombination rate, in the inhibition of QA- to QB electron transfer, and eventually to inhibition of charge separation. Comparisons of centers with ubiquinone or anthraquinone in the QA site, in which the charge recombination pathways are different, indicate that trypsination affects charges close to the QA(-)-binding site. Studies of light-induced voltage changes from moving charges in reaction centers incorporated in lipid layers on a Teflon film, a technique which allows the discrimination of effects on donor and acceptor sides, indicate that the acceptor side is preferentially degraded by trypsin in the dark. Tryptic digestion during illumination generally resulted in a marked strengthening and acceleration of the effects seen already during dark treatment, but new effects were also detected in gel electrophoretic peptide patterns, in optical spectra, and in the kinetic measurements. Optical kinetic measurements revealed that the donor side of the reaction centers became susceptible to modification by trypsin during illumination as seen in the value of the binding constant for soluble cytochrome c2 which increased by a factor of 2, whereas it was much less affected after trypsination of reaction centers in the dark. The influence of illumination on the rate and mode by which trypsin acts on reaction centers indicates that changes in the protein conformation follow charge separation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779795 TI - Resonance Raman studies of the heme active site of the homodimeric myoglobin from Nassa mutabilis: a peculiar case. AB - A spectroscopic investigation by resonance Raman has been carried out at pH 7.0 in 0.1 M phosphate buffer on the cooperative homodimeric myoglobin from Nassa mutabilis. The study has been performed on the unligated ferrous form, as well as on the ligated species MbO2 and MbC, and on the ferric form met-Mb. Two v(C = C) vinyl stretching modes have been observed in all the investigated forms, reflecting different degrees of vinyl conjugation with the porphyrin ring, as a consequence of a strongly asymmetric environment for the two side groups of the heme. Furthermore, the ferric form displays a hexacoordinate low-spin heme, which suggests the presence of an endogenous ligand bound to the Fe atom. The frequency of the v(Fe-Im) stretching mode of Mb from Nassa mutabilis shifts down by 4 cm-1 as compared with that of horse heart myoglobin, reflecting a protein-induced proximal strain as a result of heme-heme interaction due to the close proximity of the two hemes in the dimer. The lower frequency of the v(Fe-Im) stretching mode agrees well with the lower affinity for oxygen binding found for Nassa mutabilis Mb and with the slight heme core expansion with respect to horse heart Mb, suggesting a critical role for the Fe-His bond on the heme's function and structure. PMID- 7779796 TI - Substrate determinants of the course of tartrate dehydrogenase-catalyzed reactions. AB - The substrate specificity of tartrate dehydrogenase has been probed using a series of alternative substrates to identify the molecular interactions which determine whether a particular substrate undergoes enzyme-catalyzed decarboxylation or not. A series of 3-substituted malate analogs, in which F, Cl, Br, I, SH, or NH2 substituents were placed at the 3R- or 3S-position, was prepared, and the product resulting from the action of tartrate dehydrogenase on each compound was identified. All of the halomalates and both diastereomers of aminomalate underwent oxidative decarboxylation; both diastereomers of 3 thiomalate underwent net nonoxidative decarboxylation. The results were interpreted in terms of a model in which decarboxylation is conformationally controlled. The data are not consistent with a model which suggests that substrates assume the conformation that is necessary to avoid steric crowding between the enzyme and the substituent at the 3-position of the substrate. These data are consistent with a model in which the course of the reaction with (+) tartrate and meso-tartrate is dictated by the coordination of the substrate hydroxyls to the active site Mn2+. However, the observed reactivities of the 3 methyltartrate diastereomers are not consistent with this model, either: (2R,3R) 3-methyltartrate undergoes oxidative decarboxylation, and (2R,3S)-3 methyltartrate undergoes simple oxidation. These results suggest that for these compounds the conformation is dictated by the positioning of the hydrophobic substituent in a specific binding pocket.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779797 TI - Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. AB - Phenylalanine hydroxylase converts phenylalanine to tyrosine utilizing a tetrahydrobiopterin cofactor. Several key mechanistic questions have yet to be resolved, specifically the identity of the hydroxylating species and the role of the non-heme iron which is present in all of the mammalian PAHs. Recently, we have demonstrated that a bacterial PAH from Chromobacterium violaceum does not require any redox active metal for activity [Carr, R. T., & Benkovic, S. J. (1993) Biochemistry 32, 14132-14138]. To identify the function of iron in the mammalian PAH's, we have undertaken a series of experiments to compare the mechanisms of this metal-independent PAH with the iron-dependent PAH from rat liver. Using [4-2H]phenylalanine as a substrate gave a kinetic isotope effect on hydroxylation of unity for CVPAH which is in agreement with previous values reported for RLPAH. The [4-2H]phenylalanine underwent an NIH shift upon hydroxylation by CVPAH. The extent of deuterium retention at the 3-position of the tyrosine product was identical within experimental error for both RLPAH and CVPAH using [4-2H]phenylalanine and [2,3,5,6-2H]phenylalanine as substrates. This suggests that PAH from either source probably does not directly mediate the NIH shift mechanism. No uncoupled pterin turnover was observed for CVPAH with either L-tyrosine or p-chloro-L-phenylalanine as substrate or tetrahydropterin as cofactor, each of which causes uncoupled turnover with RLPAH. CVPAH readily accepts 4-methylphenylalanine as a substrate giving 4 (hydroxymethyl)phenylalanine as the major product and 3-methyltyrosine as the only other minor product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779798 TI - Determination of subunit dissociation constants in native and inactivated CTP synthetase by sedimentation equilibrium. AB - Sedimentation equilibrium was used to correlate changes in aggregation state with active site modification of Escherichia coli CTP synthetase. The native enzyme equilibrated between monomers, dimers, and tetramers in the absence of substrates. At enzyme concentrations above 5 microM, tetramers represented 40% of the species in solution. Inactivation by 6-diazo-5-oxonorleucine (DON) or thiourea dioxide reduced the amount of tetramer to below detectable limits. However, inactivated enzyme still equilibrated between monomers and dimers. Simultaneous analysis of multispeed data at three protein concentrations yielded estimates of the dissociation constants for the monomer-dimer and dimer-tetramer equilibria. For multiple data sets of native enzyme, K1,2 was between 1 and 2 microM, and K2,4 was between 1 and 18 microM. For DON inactivated enzyme, K1,2 was 3-4 microM, and for thiourea dioxide inactivated enzyme, K1,2 was approximately 1 microM. The values for K1,2 are consistent with previously published studies by gel filtration, demonstrating that the enzyme dissociates to monomers in very dilute solution (Anderson, 1983). However, the sedimentation equilibrium experiments are the first to show that the enzyme forms tetramers in the absence of nucleotides. This result implies the presence of stable conformations in the native enzyme capable of dynamic equilibrium between monomers, dimers, and tetramers. The results presented here illustrate the sensitivity of sedimentation equilibrium for measuring the aggregation state of equilibrating enzyme species and demonstrate that active site modifications disrupt the quaternary structure of CTP synthetase. PMID- 7779799 TI - Tritium isotope effects in adenosylcobalamin-dependent glutamate mutase: implications for the mechanism. AB - The transfer of tritium between adenosylcobalamin and substrate in the reaction catalyzed by glutamate mutase was examined to investigate the possibility of a protein-based radical intermediate. There was no evidence that tritium was transferred to the protein during the reaction, as tritium neither became stably bound to the protein nor exchanged with water. The kinetics of tritium transfer from adenosylcobalamin to 3-methylaspartate was investigated. Both the transfer of tritium to product and the exchange of enzyme-bound and free coenzyme contribute to the kinetics of tritium loss from adenosylcobalamin. By varying the experimental conditions, the rates of both coenzyme exchange and tritium transfer could be measured. Exchange of adenosylcobalamin with enzyme is very slow, k off = 0.01 s-1, which may reflect a conformational change in the coenzyme and/or protein involved in forming active holo enzyme. The rate constants for the loss of tritium from adenosylcobalamin and the appearance of tritium in 3 methylaspartate are much faster and very similar, k = 0.67 +/- 0.05 s-1 and k = 0.50 +/- 0.05 s-1, respectively, consistent with the transfer of tritium occurring directly between coenzyme and substrate. The isotope effect, calculated from the rate constants for tritium transfer, and kcat, determined for the overall reaction under the same conditions, are between 13.5 and 18. These values are typical of primary isotope effects seen for enzymes in which hydrogen transfer is substantially rate limiting. A protein radical, therefore, appears unlikely to feature in the mechanism of this enzyme. PMID- 7779801 TI - Nucleoplasmin-mediated decondensation of Mytilus sperm chromatin. Identification and partial characterization of a nucleoplasmin-like protein with sperm-nuclei decondensing activity in Mytilus californianus. AB - We have been able to induce sperm nuclear decondensation in the mussel Mytilus californianus (mollusc) using either egg extracts or pure nucleoplasmin from Xenopus (amphibian). The nuclear decondensation involves removal of the sperm nuclear basic proteins (SNBPs) which bind to nucleoplasmin. An attempt has been made to isolate an ooplasmic factor from Mytilus with a similar sperm-chromatin decondensing activity. An acidic, thermostable protein with a molecular mass of 58,000 has been purified and partially characterized. PMID- 7779800 TI - A heuristic approach to the analysis of enzymic catalysis: reaction of delta-(L alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate and delta-(L-alpha aminoadipoyl)-L-cysteinyl-D-allylglycine catalyzed by isopenicillin N synthase isozymes. AB - Isopenicillin N synthase (IPNS) catalyzes the oxidative cyclization of delta-(L alpha-aminoadipoyl)-L-cysteinyl-D-valine to isopenicillin N. It is proposed that the multiple products produced from certain substrate analogues result from pathway branching after formation of a ferryl oxene intermediate. We have been interested in ascertaining the reasons for multiple product formation. One possibility is that the products are predisposed toward formation once the beta lactam ring and the ferryl oxene are produced. Alternately, the products may be persuaded into being by the enzyme restricting conformations such that otherwise less favorable chemistry can take place. With the existing description of the IPNS catalytic cycle, this fundamental question has not been answerable. We describe here the application of a heuristic method to resolve this key issue. It was reasoned that by comparing the ratios of products formed by a set of perturbed IPNS variants it might be possible to generate qualitative information about the relative magnitude of certain activation parameters. If certain product ratios are affected but others are not, then it should be possible to say which steps in the reaction are dictated merely by chemical fundamentals and which steps are directly effected by the enzyme. In this paper we report the high-level expression, purification, and characterization of four IPNS isozymes. Comparison of the product ratios obtained on incubation of unnatural substrate analogues with four IPNS isozymes corresponding to perturbed active site variants shows substantial variation in some cases and little in others. Interpretation of the results obtained with delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha aminobutyrate (ACAB) allows conclusions to be drawn regarding the role of the enzyme in restricting available conformations of the natural substrate to disfavor certain otherwise chemically favorable pathways and hence products. The results obtained with delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-allylglycine, while rather more complex, substantiate the conclusions drawn from the ACAB data. A major conclusion is that, in the oxidation of ACV, IPNS is a negative catalyst of cepham formation but a positive catalyst of penam formation. PMID- 7779802 TI - The crystal structure of r(CCCCGGGG) in two distinct lattices. AB - The structure of the RNA octamer r(C4G4) has been determined in two different crystal forms. The conformations of the RNA duplex in the rhombohedral and hexagonal lattices display only minimal deviations, demonstrating that the RNA double helix is considerably less deformable than the DNA double helix. For the first time the crystal structures of an A-RNA and an A-DNA with identical sequence can now be compared. The large number of ordered water molecules observed in the minor groove of the RNA duplex suggests that an important contribution to its higher rigidity derives from the improved hydration due to the presence of the 2'-hydroxyl groups. Our finding that the conformation of the RNA double helix is virtually unaffected by different crystal packing modes provides evidence that proteins may not alter the conformation of RNA stem regions in a significant way. PMID- 7779803 TI - Cyanide and carbon monoxide binding to the reduced form of cytochrome bo from Escherichia coli. AB - Cyanide binds to fully reduced cytochrome bo and induces a blue shift of the Soret absorption band of the high-spin heme o and a change in the visible region spectrum consistent with the expected conversion to a low-spin state. The dissociation constant, determined by titration of the extent of the binding spectrum, is 7.0 +/- 0.6 mM at pH 7.0. In contrast, cyanide does not bind significantly in this concentration range to the reduced form of cytochrome bd. The reduced cyanide compound of cytochrome bo can be laser photolyzed. Typically, less than 20% photolysis was attained with conditions that give essentially full photolysis of the carbon monoxide compound. The subsequent monophasic kinetics of recombination of cyanide at varying cyanide concentrations were used to determine kon, koff, and dissociation constant values at pH 7.0 of 572 +/- 43 M-1 s-1, 4.2 +/- 0.7 s-1, and 7.3 +/- 1.3 mM, respectively. The dissociation constant changes very little in the pH range 6-8, indicating that a proton is bound together with the cyanide anion, as predicted by our recent proposal of a requirement for electroneutrality in the binuclear center [Mitchell, R., & Rich, P. R. (1994) Biochim. Biophys. Acta 1186, 19-26]. Competition studies confirm that cyanide and carbon monoxide cannot bind simultaneously, so that their binding sites must overlap. A small fraction of the reduced unliganded enzyme appears to have a distinct photolysis spectrum in the absence of added ligands, and this is transformed into a typical ferrous cyanide compound only at very high cyanide concentrations. Cyanide binding and photolysis were also examined in a number of mutant forms of cytochrome bo, and in a wild-type form which was partially depleted in CuB. Dramatic changes in rate constants and binding constants were found in several cases. Data from several mutants were compared with analogous data on the binding and photolysis of carbon monoxide, and the effects of mutation were quite different with the two ligands. A model is developed to explain the observed effects of point mutations on the recombination kinetics of both carbon monoxide and cyanide. Overall, the results indicate that the CuB site is required for binding of cyanide, but not carbon monoxide, to the reduced enzyme, possibly by providing the site for binding of the associated proton. PMID- 7779804 TI - Analysis of site-directed mutants locates a non-redox-active metal near the active site of cytochrome c oxidase of Rhodobacter sphaeroides. AB - Substoichiometric amounts of Mn are bound by the aa3-type cytochrome c oxidase of Rhodobacter sphaeroides and appear in the EPR spectrum of the purified enzyme as signals that overlay those of CuA in the g = 2.0 region. The Mn is tightly bound and not removed by a high degree of purification or by washing with 50 mM EDTA. The amount of bound Mn varies with the ratio of Mg to Mn in the growth medium. Oxidase containing no EPR-detectable Mn can be prepared from cells grown in low Mn/Mg, while high Mn/Mg in the growth medium gives rise to near stoichiometric levels (0.7 mol/mol of aa3). Incubation of purified Mn-deficient oxidase with 1 mM Mn does not allow incorporation into the tight binding site, indicating that this site is not accessible in the assembled protein. When bound Mn is depleted by growth in high Mg, there is no change in electron transfer activity, suggesting that Mg may substituted for Mn and maintain protein structure. Analysis of site-directed mutants in an extramembrane loop close to the active site of cytochrome oxidase identifies His-411 and Asp-412 of subunit I as probable ligands of the Mn. Mutation of either residue leads to lower activity and loss of Mn binding, even in cells grown in elevated concentrations of Mn. Since Mn binding correlates with the [Mn] to [Mg] ratio in the culture medium, we propose that Mn competes for the site that normally binds a stoichiometric Mg ion in aa3-type cytochrome c oxidases. PMID- 7779805 TI - A continuous wave and pulsed EPR characterization of the Mn2+ binding site in Rhodobacter sphaeroides cytochrome c oxidase. AB - The ligation environment of the tightly bound Mn2+ in cytochrome c oxidase from Rhodobacter sphaeroides has been characterized by electron paramagnetic resonance (EPR) and electron spin echo envelope modulation (ESEEM). The EPR data show that the Mn2+ is six-coordinate and located in a highly symmetric binding site. Analyses of X- and Q-band EPR spectra show that the zero field splitting parameter D is 115 +/- 25 G (0.0107 +/- 0.0023 cm-1) in the fully oxidized enzyme and 125 +/- 15 G (0.0117 +/- 0.0014 cm-1) in the fully reduced enzyme. For both redox forms of the enzyme the value of E is < or = 25 G (0.0023 cm-1). By comparison with crystal structures of Mn2+ binding proteins, the structural changes at the Mn2+ binding site upon redox state change of the enzyme are estimated to be < or = 0.2 A in ligand bond lengths and < or = 10 degrees in bond angle. This analysis indicates that little modification occurs at the Mn2+ site upon redox change at the other metal centers. Considering the proximity of the Mn2+ site to heme a and heme a3-CuB [Hosler, J. P., Espe, M. P., Zhen, Y., Babcock, G. T., & Ferguson-Miller, S. (1995) Biochemistry 34, 7586-7592], we interpret these results to imply also that there is no large protein conformational change near the heme a and heme a3-CuB sites upon a change in their redox states. Multifrequency 3-pulse ESEEM results provide direct evidence for a nitrogen ligand to the Mn2+, which is assigned to a histidine by comparison with ESEEM studies of Mn(2+)-bound lectins [McCracken, J., Peisach, J., Bhattacharyya, L., & Brewer, F. (1991) Biochemistry 30, 4486-4491] and specifically to His-411 in subunit 1 on the basis of mutagenesis studies (Hosler et al., 1995). From these results a partial model of the Mn2+ binding site has been constructed. PMID- 7779807 TI - Molecular dynamics simulations of isolated helices of myoglobin. AB - The apo form of myoglobin has two non-native stable states that have been experimentally characterized. Investigation of these states has suggested possible folding pathways for myoglobin. We have performed molecular dynamics simulations on solvated isolated helices of myoglobin to investigate the relationship between the intrinsic stabilities of the isolated helices and the structure and folding pathway of apomyoglobin. Analyses of hydrogen bonding and fluctuations from simulations at 298 and 368 K are used to explore the relative stabilities of the helices of myoglobin. The ordering observed is A approximately G approximately H > B > E > F, which mirrors both the experimental equilibrium and kinetic data available for apomyoglobin. The experimental observation that a subdomain comprising helices A, G, and H is an important early intermediate and our result that these helices are the most stable suggest that the intrinsically more stable helices form early in the folding process and that this significantly influences the folding pathway. PMID- 7779806 TI - Solution structure of the cytoplasmic domain of phopholamban: phosphorylation leads to a local perturbation in secondary structure. AB - Peptides representing the N-terminal domain (Ia) of the cardiac sarcoplasmic reticulum protein phospholamban (residues 1-25 [PLB(1-25)] and a phosphorylated form [pPLB(1-25)]) were synthesized and their conformations examined using circular dichroism and nuclear magnetic resonance spectroscopy. In aqueous solution, both PLB(1-25) and pPLB(1-25) adopt a primarily disordered conformation. In 30% trifluoroethanol/10 mM phosphate, PLB(1-25) exhibits a CD spectrum consistent with 60% helical structure. This value decreases to 27% for the phosphorylated peptide. CD spectra in 2% SDS indicate 40% alpha-helix for PLB(1-25) and 20% for pPLB(1-25). Full chemical shift assignments were obtained by conventional homonuclear NMR methodologies for both PLB(1-25) and pPLB(1-25) in 30% trifluoroethanol/water and 300 mM SDS. The solution structure of PLB(1-25) in 30% TFE/water was determined from distance geometry calculations using 54 NOE distance constraints and 17 torsion angle constraints. In the family of 20 calculated conformers, the root mean square deviation from the mean structure is 0.79 A for backbone heavy atoms of residues 1-17. The structure comprises a regular alpha-helix extending from M1 to S16 with the remaining C-terminal residues disordered. The calculated structure is supported by analysis of C alpha H secondary shifts which are significantly negative for residues 1-16. Chemical shift degeneracy is substantially more extensive in the phospho form and precludes a direct comparison of calculated structures. However, the magnitudes of upfield secondary shifts are decreased by 20% in residues 1-11 and are not significantly helical for residues 12-16 according to the criteria of Wishart et al. [(1992) Biochemistry 31, 1647-1651]. 3JHN alpha coupling constants measured for I12, R13, A15, and S16 also suggest that residues 12-16 undergo a local unwinding of the helix upon phosphorylation. Similar results are obtained for PLB(1-25) and pPLB(1-25) in 300 mM perdeuterated sodium dodecyl sulfate except that differences in backbone dynamics for the helical and nonhelical regions of the peptide are evident in the DQF-COSY line shapes for fingerprint cross-peaks. This disruption of structure at the C-terminus of the helix suggests a model for phosphorylation-induced dissociation of the PLB/Ca(2+)-ATPase complex. PMID- 7779808 TI - Solution structure of the C-terminal single-stranded DNA-binding domain of Escherichia coli topoisomerase I. AB - Escherichia coli DNA topoisomerase I catalyzes the interconversion of different topological forms of DNA. In this paper we describe NMR studies of a 14K C terminal fragment of this enzyme that binds preferentially to single-stranded DNA and enhances the enzyme's ability to relax negatively supercoiled DNA under high salt conditions. The 1H, 13C, and 15N resonances of the protein were assigned from a number of heteronuclear multidimensional NMR experiments, and the three dimensional structure of the protein was determined from a total of 2188 NMR derived restraints. The root-mean-square deviation about the mean coordinate positions for residues 13-120 is 0.68 +/- 0.11 A for the backbone atoms and 1.09 +/- 0.09 A for all heavy atoms. The overall fold, which consists of two four stranded beta-sheets separated by two helices, differs from other DNA- and RNA binding proteins such as gene 5, cold shock protein, and hnRNP C. From an analysis of the changes in chemical shift upon the addition of single-stranded DNA, the location of the oligonucleotide binding site was determined. The binding site consists of a beta-sheet containing positively charged and aromatic amino acids and, in spite of its different structure, is similar to that found in other proteins that bind single-stranded oligonucleotides. PMID- 7779809 TI - pH-dependent conformations of the amyloid beta(1-28) peptide fragment explored using molecular dynamics. AB - Molecular dynamics simulations were used to successfully reproduce the experimentally observed pH-dependent conformational behavior of a monomeric peptide in aqueous solution. Simulations were conducted at 298 K on a peptide corresponding to residues 1-28 of the amyloid beta-peptide [referred to as beta(1 28)], which is the primary component of the plaques associated with Alzheimer's disease. beta(1-28) was found to be entirely alpha-helical at low pH. Upon deprotonation of acidic residues at medium pH, helical structure was lost in the N-terminal region. At high pH, some secondary structure was recovered to yield two helices joined by a kink. These results are in good agreement with the NMR solution structure at low pH [Zagorski and Barrow (1992) Biochemistry 31, 5621 5631; Talafous et al. (1994) Biochemistry 33, 7788-7796] and CD and NMR evidence of an alpha-helix to beta-sheet transition at mid-range pH [Barrow et al. (1992) J. Mol. Biol. 225, 1075-1093]. Additional simulations were also able to regenerate folded species from partially unfolded conformers. A mechanism for the pH-dependent structural rearrangements is proposed that involves the creation of a hydrogen-bonded pair between Ser 8 and Glu 11. The evidence for the existence of a multiconformational equilibrium of folded and unfolded species of the peptide is discussed. PMID- 7779810 TI - Sequence effects on the conformational properties of the amyloid beta (1-28) peptide: testing a proposed mechanism for the alpha-->beta transition. AB - Molecular dynamics simulations have been used to successfully reproduce the observed pH-dependent conformational properties of the amyloid beta(1-28) peptide [Kirshenbaum and Daggett (1995) Biochemistry, 34, 7629-7639]. On the basis of these simulations a mechanism was proposed for the unfolding of the N-terminal portion of the peptide at neutral pH when beginning from the helical conformation. It was proposed that interactions between the side chains of Ser 8 and Glu 11 are important in determining the pH dependence of the helix content. Here we further investigate this proposed mechanism and the residues involved in the conformational transition by performing computational "mutagenesis" studies. On the basis of simulations of the mutant peptides, the importance of the Ser 8 Glu 11 interaction is substantiated, and further details of the conformational transition are elucidated. PMID- 7779811 TI - Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene. AB - The promoter of the cell cycle regulated histone FO108 H4 gene is mediated by two in vivo protein/DNA interaction domains, sites I and II. We have shown previously that site II mediates the cell cycle controlled enhancement of H4 gene transcription at the G1/S phase boundary. Here we show that site I, an element containing both G-rich and ATF-like consensus sequences, confers maximal levels of transcription in proliferating cells. By the combined application of gel shift assays with site-directed mutagenesis, DNase I footprinting, oligonucleotide competition, in vitro expression of recombinant proteins, and specific antibody supershift studies, we demonstrate that the proximal G-rich sequence within site I interacts with the transcription factor Sp1, while the distal portion of site I interacts with members of the ATF family of proteins, including ATF-1. In vitro transcription studies as well as expression assays of transiently and stably transfected genes in HeLa cells reveal that the deletion of site I causes a dramatic decrease in expression. Mutation of the Sp1 element, which abolishes Sp1 binding, results in a 6-10-fold reduction in reporter activity. In addition, overexpression of Sp1 in Sp1-deficient cells results in the dramatic activation of the histone promoter. In contrast, mutation of the asymmetric ATF binding site, located distally within site I, has a more limited effect upon expression. Interestingly, the contribution of the Sp1 site to maximal transcription was cell type dependent. Thus, we demonstrate that the Sp1 binding site of the site I histone H4 promoter in particular is critical for maximal expression in living cells and postulate that this site may act to amplify the cell cycle response. PMID- 7779812 TI - Inhibition of nuclear protein binding to two sites in the murine c-myc promoter by intermolecular triplex formation. AB - The c-myc gene is overexpressed in a variety of tumor types and appears to play an important role in the abnormal growth of a number of cell types. In an effort to determine the ability of sequence- and species-specific triplex-forming oligonucleotides to inhibit expression of a targeted gene in animals, we have identified two novel triplex-forming sites in the murine c-myc promoter. One is homologous to the triplex-forming human PuF binding element located upstream of the P1 transcription start site. The other triplex-forming site is found in a region between P1 and P2 that encompasses the ME1a1 binding site and part of the E2F binding site and is highly homologous to the human sequence. Synthetic oligodeoxyribonucleotides designed to target these essential regulatory elements form sequence-specific triple helices as demonstrated by gel mobility shift analysis and DNase I footprinting. Polypurine: polypyrimidine regions in the P1 and P2 promoters form specific protein-DNA complexes upon incubation with a murine YC8 nuclear extract. Preincubation of each of the promoter fragments with its respective triplex-forming oligonucleotide results in the inhibition of nuclear protein binding. Non-triplex-forming oligonucleotides do not significantly affect protein binding. The data presented are a preliminary step toward generating an animal model for the phenotypic effects of triplex formation within the c-myc promoter. PMID- 7779814 TI - Stereoelectronic activation of methylenetetrahydrofolate by thymidylate synthase: resonance Raman spectroscopic evidence. AB - Resonance Raman (RR) spectra are reported for the ternary complex of Escherichia coli thymidylate synthase with the cofactor 5,10-methylenetetrahydrofolate (CH2 H4-folate) and the inhibitor 5-fluoro-2'-deoxyuridylate, excited at 337 or 356 nm, in resonance with perturbed absorption bands of the p-aminobenzoylglutamate (PABA-Glu) portion of the cofactor. For comparison, RR spectra were obtained with 260 nm excitation for PABA-Glu in various solvents, and for CH2H4-folate and H4 folate in aqueous solution. These reference spectra are assigned to modes of PABA Glu in its benzenoid form. The ternary complex RR spectra are very different, however, and are assigned, with the aid of isotopic data, to the PABA-Glu in a predominantly quinoid form. Similar spectra were obtained for the ternary complexes of the E58Q and K48Q mutants, indicating that neither Glu58 nor Lys48 are essential for maintaining the quinoid structure, even though their side chains complement the dipolar charge distribution of the quinoid form of PABA Glu. Since these are the only charged residues in the PABA-Glu vicinity, electrostatic stabilization is not essential to maintenance of the quinoid structure. It is proposed that quinoid formation results from steric forces, probably resulting from the protein conformation change known to accompany cofactor binding, which enforce coplanarity of the PABA-Glu ring and substituents. This stereoelectronic change activates the cofactor by opening the methylene bridge. A second RR spectrum of the ternary complex, previously proposed to reflect an alternate structure, is shown to result instead from irreversible formation of a laser-induced photoproduct. PMID- 7779813 TI - Heteronuclear NMR studies of the interactions of 15N-labeled methionine-specific transfer RNAs with methionyl-tRNA transformylase. AB - In Escherichia coli the methionylated initiator methionyl-tRNA (tRNAfMet) is formylated on the aminoacyl moiety by the enzyme methionyl-tRNA transformylase. The methionylated elongator methionyl-tRNA (tRNAmMet) is not modified in this way. In order to gain structural information about this specific recognition, solution NMR studies were carried out. To be able to identify changes that were occurring in the tRNA molecule on interaction with the methionyl-tRNA transformylase, the imino protons involved in secondary and tertiary base pairing in the tRNAfMet and tRNAmMet molecules first had to be assigned to specific resonances in the NMR spectra. A combination of 2D NOESY, 2D HMQC, and 3D NOESY- HMQC spectra were used on uniformly 15N-labeled samples. After assignment of the base pairs of the tRNA, the two forms of tRNA were separately mixed with transformylase in a 1:1 molar ratio. The HMQC spectra of both the tRNAmMet and the tRNAfMet showed general broadening, but in the tRNAfMet HMQC spectra a decrease in the intensity of several resonances was also observed. These resonances had been assigned to the acceptor stem of the tRNA, confirming site directed mutagenesis experiments that it is the acceptor stem of the tRNA which is important in conferring the specificity for the transformylase. The loss of intensity of the acceptor stem resonances suggests that this part of tRNAfMet melts upon binding to the enzyme. PMID- 7779815 TI - Resonance Raman characterization of the binary and ternary complexes of thymidylate synthase with 5-nitrodeoxyuridylate. AB - Resonance Raman (RR) spectra are reported for the binary complex of Escherichia coli thymidylate synthase (TS) with the substrate analog inhibitor 5 nitrodeoxyuridylate (NDU). The TS/NDU binary complex RR spectrum shows many similarities to the RR spectra of thiol adducts of NDU or of 5-nitro-1 methyluracil formed in solution, providing strong evidence in support of the formation of a covalent link between Cys146 of TS and C6 of NDU. Spectral differences between the model compounds and the binary complex reflect the consequences of fixing the conformations of the uracil and ribose rings at the enzyme active site. The RR spectra of the ternary complexes of TS/NDU with either tetrahydrofolate (H4-folate) or the cofactor 5,10-methylenetetrahydrofolate (CH2H4-folate) show that a covalent link is not formed between C11 of CH2H4 folate and C5 of NDU. Neither does the methylene bridge of CH2H4-folate remain intact in the ternary complex; either CH2H4-folate is present as the N5 iminium cation species or the methylene group is lost as formaldehyde. A shift in the NO2 symmetric stretching frequency in the ternary complex indicates expulsion of water molecules from the region of the NO2 group by the cofactor. PMID- 7779816 TI - Involvement of histidine-91 of the beta subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli. AB - The pyridine nucleotide transhydrogenase (EC 1.6.1.1) carries out transmembrane proton translocation coupled to transfer of a hydride equivalent between NAD+ and NADP+. Mutations were made in histidine-91 of the beta subunit of the pyridine nucleotide transhydrogenase of Escherichia coli. This amino acid is the only conserved charged residue in the transmembrane domains of this enzyme and thus potentially is involved in proton translocation by the transhydrogenase. The mutant beta H91N retained 80% of the hydride transfer activity while proton translocation was reduced to 7%. This behavior is consistent with a role for beta His91 in the proton translocation pathway. Other mutations at this residue affected the conformation of the enzyme. Thus, the enzyme in mutants beta H91C, beta H91T, and beta H91S was unable to undergo the conformational change that occurred on binding of the substrates NADP+ or NADPH. By contrast, the enzyme in the beta H91K mutant was present in the NADP(H)-induced conformation even in the absence of these substrates. Further evidence for the linkage between beta His91 and the conformation of the beta subunit was obtained by labeling the transmembrane domain of the beta subunit with [14C]N,N'-dicyclohexylcarbodiimide (DCCD). Labeling occurred most readily with the enzyme of beta H91K. It is concluded that beta His91 is a component of the proton translocation pathway of the transhydrogenase and that its state of protonation is probably linked to conformational changes induced by binding/debinding of substrates during the catalytic cycle of the enzyme. PMID- 7779817 TI - Effect of lipid packing on the conformational states of purified GLUT-1 hexose transporter. AB - The purpose of this study was to determine the effect of increased lipid packing on the conformational states of the GLUT-1 hexose transporter purified in endogenous lipids. The binding of glucose results in a conformational change that can be followed by a decrease in fluorescence intensity. Lipid packing was increased by subjecting the samples to hydrostatic pressure. We have found that in the absence of ligand, the fluorescence intensity decreased approximately 20% in the 600 bar range studied. In the presence of either saturating or half saturating amounts of D-glucose, a substantial loss in intensity (approximately 80%) was observed. Similar decreases were also seen the presence of a glucose analog, maltose, or a noncompetitive inhibitor, cytochalasin B. Changes in the accessibility of aqueous soluble quenchers (I- and acrylamide) to GLUT-1 Trp and Tyr residues suggested that ligand binding causes interfacial fluorophores to move closer to ionic groups in the lipid head group region of the membrane. This idea was substantiated by (1) increased static quenching of the GLUT-1 fluorophores in the presence of ligand, (2) increased energy transfer efficiency between GLUT-1 fluorophores and a fluorescent membrane probe located close to the head group region, and (3) reduced change in rotational motion with temperature in the presence of ligand. Since the application of pressure results in an increase in bilayer thickness, and ligand binding causes a population of fluorophores to move closer to the membrane surface, then these interfacial interactions can be more stabilized under pressure. Studies monitoring the change in quenching of membrane probes by GLUT-1 tryptophans and energy transfer of GLUT 1 tryptophans to membrane probes support this idea. PMID- 7779818 TI - Synthetic peptides corresponding to the four P regions of Electrophorus electricus Na+ channel: interaction with and organization in model phospholipid membranes. AB - The hydropathy plot of the alpha subunit of the voltage-gated Na+ channel reveals four homologous repeats, each of which is homologous to Shaker type K+ channel monomer and contains six putative transmembrane segments and a hydrophobic segment within the loop connecting transmembrane segments S5 and S6. Current models predict that the four homologous segments [designated H5 or P regions (PR)] from the S5-S6 loop of each repeat lie in the aqueous pore. Peptides corresponding to the P regions of the four domains of the Electrophorus electricus (eel) Na+ channel (25-36 aa long, designated as PR-I, PR-II, PR-III, and PR-IV) and a 23-mer preceding PR-II (designated pre-PR-II) were synthesized and fluorescently labeled. The segments were then structurally and functionally characterized for their interaction with phospholipid membranes. Although the sequences of the four P regions are significantly different, they all bind to zwitterionic phospholipid membranes with similar partition coefficients (approximately 10(4) M-1). The pre-PR-II does not bind membranes at all. Resonance energy transfer measurements, between donor/acceptor-labeled pairs of peptides, revealed that besides the PR-I/PR-III pair, all other pairs form heteroaggregates but do not coassemble with unrelated membrane-bound peptide. Circular dichroism (CD) spectroscopy revealed that PR-I, PR-II, and PR-III adopt similar partial alpha-helical structures (approximately 30%) in 40% trifluoroethanol and in solutions of 1% sodium dodecylsulfate (SDS). The PR-IV (36 aa) adopts approximately 18% alpha-helical structure, and pre-PR-II gives a low CD signal. These findings are in line with proposed models in which the P regions are packed in close proximity in the lumen of the hydrophobic core of the channel. Furthermore, the finding that the PRs adopt similar partial alpha helical structures in two different hydrophobic environments might suggest that partial alpha-helical structures also exist in the native channel as proposed by recent models. The results are discussed in terms of proposals that various regions of membrane proteins participate in driving folding or oligomerization of the parent molecules. PMID- 7779819 TI - Functional significance of beta gamma-subunit carboxymethylation for the activation of phospholipase C and phosphoinositide 3-kinase. AB - The gamma subunits of heterotrimeric G proteins are isoprenylated and methylated at their carboxyl-terminal cysteine residues. Since methylation is the only reversible reaction in the isoprenylation pathway, it could be a site of regulation of G protein activity. beta gamma subunits have been shown to activate a number of effectors involved in signal transduction pathways. The methyl group of retinal transducin (T) can be hydrolyzed by an immobilized form of pig liver esterase, allowing for a direct determination of the activities of methylated and demethylated T beta gamma. The abilities of methylated and demethylated T beta gamma to stimulate G protein regulated phosphatidylinositol-specific phospholipase C (PIPLC) and phosphoinositide 3-kinase (PI3K) were determined. It is reported here that there is a strong dependence on methylation for activating both PIPLC and PI3K. Demethylated T beta gamma is at least 10-fold less active than its methylated counterpart. Therefore, methylation may play an important role in the regulation of these effectors and of signal transduction processes in general. PMID- 7779820 TI - An improved version of the hairpin ribozyme functions as a ribonucleoprotein complex. AB - Most RNA molecules that are endowed with catalytic activity function in the form of ribonucleoproteins within cells. These complexes are frequently large, poorly defined, and difficult to study. As a model system to study biological catalysis by ribonucleoproteins, we have modified the hairpin ribozyme by inserting an RNA structure that serves as a binding site for bacteriophage R17 coat protein in the form of an extension to ribozyme helix 4, which lies at the periphery of the catalytic domain. In the absence of protein, we find that incorporation of the protein-binding domain increases the catalytic efficiency of the hairpin ribozyme by 2-fold for the cleavage reaction and 16-fold for the ligation reaction. This increase in activity correlates with an increase in the proportion of molecules which fold into the active tertiary structure, as measured by a UV cross-linking assay. Mobility-shift and filter-binding assays of complex formation show that R17 coat protein binds to the chimeric ribozyme with a dissociation constant essentially identical to that of the isolated protein-binding domain; no binding of the protein to the unmodified ribozyme could be detected. The kinetics of cleavage and ligation reactions are not altered by the presence of saturating concentrations of coat protein, and competition studies demonstrate that the protein remains bound to the ribozyme throughout the catalytic cycle. These studies establish that the hairpin ribozyme can be engineered to function efficiently in the form of a ribonucleoprotein in vitro and will serve as the basis for future experimentation to understand mechanisms of protein modulation of catalytic RNA activity, and to introduce other protein-binding domains, for example, HIV-1 rev-binding and tar elements, which may be useful for influencing subcellular localization, regulating intracellular activity, or generating ribozymes that also function as "decoys" in antiviral applications. PMID- 7779821 TI - Nature of the inactivation of elastase by N-peptidyl-O-aroyl hydroxylamine as a function of pH. AB - The mechanism of inactivation of porcine pancreatic elastase (PPE) by N-peptidyl O-aroylhydroxylamine was studied by X-ray crystallography. The inactivator forms a stable complex with the enzyme by means of a covalent attachment to the active site Ser 203(195) O gamma. The nature of the complex is, however, different depending on the pH at which the inactivation reaction occurs. At pH 5, the complex formed is a hydroxylamine derivative of Ser 203(195) in which the O gamma of serine is the oxygen of the hydroxylamine derivative. At pH 7.5, the complex formed is a carbamate derivative at Ser 203(195) O gamma. In both types of complexes, the inactivator binds in the S' subsites of the enzyme instead of forming the usual antiparallel beta-sheet with the S subsites. The implication for the mechanism of inactivation at different pHs is discussed. PMID- 7779822 TI - Role of asparagine 152 in catalysis of beta-lactam hydrolysis by Escherichia coli AmpC beta-lactamase studied by site-directed mutagenesis. AB - The role of asparagine 152 in the catalytic mechanism of Escherichia coli AmpC beta-lactamase has been investigated by site-directed mutagenesis. The residue has been replaced by aspartic acid, glutamic acid, histidine, and leucine. All the substitutions had similar effects on the activity toward substrates and inhibitors. The rate of substrate hydrolysis decreased by factors of 500-5000. The rates of both acylation (2-50-fold decrease) and deacylation (50-500-fold decrease) were affected, indicating a role for Asn152 in both processes. The wild type AmpC beta-lactamase appears to exist as an equilibrium mixture of two forms, identified by their different kinetic properties. The Asn152 mutations affected the activity of the slow-reacting form much more than that of the fast-reacting form, but they did not appear to affect the interconversion of these two kinetic forms. Comparison of these observations with results obtained with mutation of the equivalent residues in other classes of penicillin-sensitive enzyme indicates that there are quite profound differences between the catalytic mechanisms of these enzymes despite a high degree of conservation of amino acids in the active center, and of the overall three-dimensional structure. PMID- 7779823 TI - Lignin peroxidase-catalyzed oxidation of sulfonated azo dyes generates novel sulfophenyl hydroperoxides. AB - Lignin peroxidase (LiP) is an extracellular enzyme produced by the lignin degrading fungus Phanerochaete chrysosporium and is involved in azo dye degradation by this organism. In this study, LiP oxidation of the sulfonated azo dyes 4-(4'-sulfophenylazo)-2,6- dimethylphenol (I), Orange II [1-(4' sulfophenylazo)-2-naphthol] (II), a dimethyl analog of Orange II [1-(2',6' dimethyl-4'-sulfophenylazo)-2-naphthol] (III), and 4-(4'-sulfonamidophenylazo) 2,6-dimehtylphenol (IV) was examined. Azo dye I was oxidized to 2,6-dimethyl-1,4 benzoquinone and 4-sulfophenyl hydroperoxide. Orange II (II) was oxidized to 1,2 naphthoquinone and 4-sulfophenyl hydroperoxide. The dimethyl analog of Orange II (III) was oxidized to 1,2-naphthoquinone and 2,6-dimethyl-4-sulfophenyl hydroperoxide. Azo dye IV was oxidized predominantly to 2,6-dimethyl-1,4 benzoquinone and another product, tentatively characterized as 4 sulfonamidophenyl hydroperoxide. In the 18O-labeling studies with 18O2, oxygen incorporation into the phenyl hydroperoxides from the oxidation of I and III was observed. A mechanism for azo dye degradation consistent with product identification and the 18O-labeling studies is proposed. Two successive one electron oxidations of the phenolic ring of an azo dye by the H2O2-oxidized forms of LiP produces a carbonium ion. Then water attacks the phenolic carbon bearing the azo linkage, producing an unstable hydroxy intermediate which breaks down to yield a quinone and a sulfo- or sulfonamidophenyldiazene. The phenyldiazene is oxidized by O2 to generate the corresponding phenyldiazene radical, which eliminates N2 to yield a sulfo- or sulfonamidophenyl radical. O2 scavenges the latter to yield the corresponding hydroperoxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779824 TI - Lignin peroxidases can also oxidize manganese. AB - The peroxidase isozymes secreted by the white rot fungus Phanerochaete chrysosporium include lignin peroxidases and manganese-dependent peroxidases. The major isozymes, called lignin peroxidases, are thought to oxidize chemicals directly. The manganese-dependent peroxidases (H3, H4, H5, and H9) are relatively minor, making up only a fraction of the total peroxidase protein. However, we have found that lignin peroxidases will also catalyze the H2O2-dependent oxidation of Mn2+ to Mn3+. We have used lignin peroxidase isozyme H2 (LiPH2) to characterize the manganese peroxidase activity of lignin peroxidases. Transient state kinetic studies were used to obtain a second-order rate constant of 4.2 x 10(4) M-1 S-1 for the reaction of LiPH2-compound I with free or chelated Mn2+ at pH 6.0. This reaction was too fast to monitor at pH 4.5. Only chelated Mn2+ could reduce LiPH2-compound II to ferric enzyme. The Mn(2+)-chelate (oxalate) first bound LiPH2-compound II with a Kd of (1.5 +/- 0.3) x 10(-5) M and then reduced LiPH2-compound II to ferric enzyme with a first order rate constant of 215 +/- 6 S-1. Steady-state kinetic studies on LiPH2 were performed by directly monitoring the formation of Mn(3+)-oxalate. These results show that oxidation of Mn2+ by a lignin peroxidase does not occur through free radical mediation as proposed previously [Popp et al. (1990) Biochemistry 29, 10475-10480). Electron spin resonance and oxygen evolution studies also indicate that Mn2+ is directly oxidized by LiPH2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779825 TI - Abortion services for adolescents: who will provide them? PMID- 7779826 TI - Attention deficit disorder during adolescence: a review. AB - Attention deficit disorder (ADD) in adolescents has received scant attention when compared with that given to children. With or without hyperactivity, ADD does not disappear at puberty and is an important factor in scholastic and social failure in adolescents. As a condition associated with decreased metabolism in the premotor and prefrontal superior cerebral cortex, ADD in adolescents responds well to treatment with stimulants, tricyclic antidepressants and monoamine oxidase inhibitors. Nonpharmacologic modalities such as behavior modification, individual and family therapy, and cognitive therapy are useful adjuncts to psychopharmacologic management. Without effective treatment, ADD often results in increased risk of trauma, substance abuse and conduct and affective disorders during adolescence, and marital disharmony, family dysfunction, divorce, and incarceration in adulthood. Properly treated with medication and counseling, adolescents with ADD succeed as well as their peers. PMID- 7779827 TI - Informed consent in children and adolescents: age, maturation and psychological state. AB - PURPOSE: The purpose of this investigation was to examine the relationship of understanding of research participation to anxiety, control, and stage of cognitive development. METHODS: Participants included 44 boys and girls ages 7 to 20 years. All were inpatients for the first time in pediatric units of a research hospital. Twenty participants were admitted for experimental treatment of pediatric cancers and 24 were admitted for a 3-week treatment of extreme obesity. An interview was conducted to assess 12 elements of knowledge of research participation of a medical protocol. The interview was coded for: 1) knowledge of research participation score, 2) weighted knowledge of participation in research score (based on physician ratings of what was most-to-least important for children and adolescents to know), and 3) global control (perceived control over life, illness and treatment). A measure of anxiety and one Piagetian task to measure stage of cognitive development also were administered. RESULTS: Pearson correlations, significant at p < or = .05, were as follows: knowledge of participation in research and global control, (r = .40) and weighted knowledge of participation in research score and global control (r = .38). Hierarchical regression showed that the best predictors of knowledge of research participation or the weighted knowledge of research participation score was global control alone or an interaction of global control with anxiety. CONCLUSIONS: Emotional factors were more frequently related to understanding of research participation than age or cognitive development. Providing medical environments that decrease anxiety and increase control may enhance children's and adolescent's understanding of the research process. PMID- 7779828 TI - Relationship of alcohol expectancies to problem drinking among college women. AB - PURPOSE: To evaluate the stability of expectancies about alcohol and their ability to prospectively explain drinking patterns and the occurrence of alcohol related problems among college freshman women. METHODS: College women (n = 120) completed a standardized measure of expectations and subjective evaluations of positive and negative outcomes associated with drinking and a questionnaire assessing drinking patterns and common alcohol-related problems at both the beginning and end of the school year. Ninety percent of the students were Caucasian with a mean age of 17.9 years (SD = 0.5). RESULTS: Students' positive and negative outcome expectations and their subjective evaluations at the beginning of the year were significantly correlated with drinking patterns at the end of the year (p's < .05). During the year, students at low risk for problem drinking developed stronger positive attitudes toward the effects of alcohol upon courage, became less concerned about potential behavioral impairment, and perceived less negative effects upon self-perception. High risk students showed a significant decline in their positive attitudes toward the effects of alcohol upon their sociability. Expectancies about alcohol at the beginning of the school year explained 33% of variance in subsequent drinking (F = 6.17; p < .0004) and 20% of the variance in alcohol-related problems occurring during the year (F = 3.26; p < .02). Outcome evaluation scales at the beginning of the year explained more variance in subsequent drinking and alcohol-related problems than did outcome expectation scales. CONCLUSIONS: Alcohol outcome expectations and their subjective evaluations were relatively stable across the freshman year for these college women. Alcohol expectancies on entry into college explained significant amounts of variability in drinking behavior and the occurrence of alcohol-related problems during the subsequent freshman year. Students' attitudes toward perceived outcomes may be more important than the perceived likelihood of the outcomes themselves. PMID- 7779829 TI - Family and peer influences on smoking behavior among American adolescents: an age trend. AB - PURPOSE: To study the age trend of family and peer influence on adolescent smoking behavior using a national sample. METHODS: Adolescents (N = 6,900), ages 14 through 18 years, from the 1988-89 Teenage Attitudes and Practices Survey, were selected for analyses. Data collected included measures for smoking status of the adolescent and their family and peers. RESULTS: Peer influence, such as the smoking status of best male/female friends, proved to be the most significant and consistent predictor across all ages, while parental influence had little effect on adolescent smoking status. Gender-specific effects were noted in the peer influence of adolescent smoking. CONCLUSIONS: The peer influence on adolescent smoking, across ages 14 through 18 years, confirmed previous literature. However, no differential effect of family and peer influence on adolescent smoking was evident. PMID- 7779830 TI - The self-image of adolescents with cystic fibrosis. AB - PURPOSE: The changing expectations, therapies and outcomes for young people with cystic fibrosis (CF) necessitate a re-evaluation of the impact of this chronic illness on adolescent development. The aim of this study was to assess the psychological well-being and adjustment of contemporary adolescents with CF. METHODS: Forty-nine adolescents with CF (24 males, 25 females) aged 14-18 years were enrolled from the Royal Children's Hospital CF Clinic, Melbourne, Australia. The Offer Self-Image Questionnaire was administered to participating subjects whose growth and pubertal developmental and pulmonary function was assessed. RESULTS: The mean (SD) FEV1% was 82 (21), and mean (SD) National Institute of Health clinical score was 81 (12). There were no significant differences between males and females in pulmonary function or clinical scores, but growth and pubertal development were delayed in both sexes. Females, but not males, with CF were less well-adjusted than their healthy peers. Two-way analysis of variance was performed and showed significant sex differences in sub-scales of the Offer questionnaire numbers I, II, III, VI, VIII, IX, as well as in the total score. Age was significant only for scales II and VIII, and only scale II displayed an interaction between sex and age. CONCLUSIONS: This study suggests that adjustment and self-esteem are less than ideal in young people with CF, especially females. PMID- 7779831 TI - Fighting as a marker for multiple problem behaviors in adolescents. AB - PURPOSE: Behaviors that put adolescents at risk frequently occur together. To help identify high-risk adolescents, we analyzed a national, self-reported behavior survey of high school students to assess the suitability of fighting as a marker for students with multiple problem behaviors. METHODS: A cross-sectional cluster survey of 11,631 U.S. high school students in 1990 was used to compare the prevalence of recent problem behaviors among all students and those who fight. RESULTS: One (8%) of every 12 students was in a fight during the 30 days before the survey. Reported problem behaviors were prevalent among fighters: during the previous 12 months, 24% attempted suicide; during the previous 30 days, 26% carried a firearm, 13% used cocaine, and 39% drove a motor vehicle while intoxicated; during the previous 3 months 41% had two or more sex partners; and 45% had sexual intercourse and did not use a condom the last time they had sex. Of all students, fighters accounted for 22% of those who reported attempting suicide, 49% carrying a firearm, 46% using cocaine, 18% driving while intoxicated, 25% having sex with multiple partners, and 11% not using condoms. Three or more of these six problem behaviors were reported by 26% of the fighters. The problem behaviors were all positively correlated, and the first principal component accounted for 35% of the total variation among the individual variables. PMID- 7779832 TI - The co-morbidity of violence-related behaviors with health-risk behaviors in a population of high school students. AB - PURPOSE: To describe the frequency of violence-related behaviors and their association with other health behaviors among high school students. METHODS: The Youth Risk Behavior Survey was administered to all ninth and eleventh graders (n = 2075) of a school district in Texas. It provided information regarding violence related behaviors and other health behaviors. Students were classified into four mutually exclusive, violence-related categories according to whether they were involved in a physical fight and/or carried a weapon. RESULTS: Overall, 20% of the students were involved in a physical fight but had not carried a weapon, 10% carried a weapon but had not been involved in a physical fight, and 17% had been involved in a physical fight and had carried a weapon. Prevalence of weapon carrying and fighting were higher among males than females, and among ninth graders than eleventh graders. Among males, 48% had carried a weapon the month prior to the survey. Students who both fought and carried a weapon were 19 times more likely to drink alcohol six or more days than students who did not fight nor carried a weapon. Logistic regression analyses showed that drinking alcohol, number of sexual partners, and being in ninth grade were predictors of fighting. These three variables plus having a low self-perception of academic performance and suicidal thoughts were predictors of fighting and carrying a weapon. CONCLUSIONS: The data indicate that violence-related behaviors are frequent among high school students and that they are positively associated with certain health behaviors. Interventions designed to reduce violence should also address coexisting health-risk behaviors and target high-risk groups. PMID- 7779834 TI - Effects of long term treatment with sertraline (Zoloft) simulating hypothyroidism in an adolescent. AB - A 16-year-old depressed adolescent, who had received sertraline treatment for the previous 18 months, developed insomnia, daytime somnolence and lack of energy. His thyroid function tests revealed low levels of total T4 with normal levels of free T4 and TSH, and a normal thyrotropin-releasing hormone (TRH) stimulation test. Discontinuing sertraline resulted in improved sleep and disappearance of daytime somnolence. Although daytime somnolence and low levels of total T4 can mimic hypothyroidism, in this case sertraline only displaced the bound-fraction of total T4 and was not associated with true hypothyroidism. PMID- 7779833 TI - Self-reported health problems and physical symptomatology in adolescent alcohol abusers. AB - PURPOSE: Few studies have examined the impact of alcohol abuse on the health status of adolescents. The purpose of this investigation was to determine whether adolescents with a diagnosis of alcohol abuse differed from controls on the frequency of self-reported health problems, clinical signs and symptoms detected upon clinical examination, and liver injury test results. METHODS: Cases were ascertained from in-patient drug and alcohol treatment centers. Age- and sex matched controls were recruited from community sources. The Health Problems Checklist (HPC) was used to measure self-reported problems; the clinical examination was performed by a physician or a physician's assistant. RESULTS: Alcohol-abusing adolescents reported significantly more physical symptoms than did controls as measured by the HPC. The results of the clinical examination revealed a low prevalence of overt abnormalities in both groups, however, alcohol abusing adolescents reported a higher frequency of appetite changes, weight loss, eczema, headaches and episodes of loss of consciousness than did controls. As expected, alcohol-abusing adolescents had significantly higher levels of ALT, AST and GGTP as compared to controls. CONCLUSIONS: The findings of this study are generalizable only to in-patient adolescent alcohol abusers. In this study, alcohol abuse was also associated frequently with psychiatric disorders, drug abuse, cigarette smoking, and low parental education. Future studies using larger sample sizes should address the importance of social environmental and behavioral variables in moderating the relationship between alcohol abuse and decreased health status in adolescents. PMID- 7779835 TI - Sexual histories of adolescent girls: comparison between interview and chart. AB - PURPOSE: The purpose of this study is to determine the reliability of sexual histories obtained from adolescents and the adequacy of chart documentation by providers of adolescent health care. METHODS: Responses to an interview by a female research assistant about sexual activity were compared to chart-documented sexual histories taken by physicians and nurse practitioners. The setting was an urban, hospital-based adolescent clinic. The subjects were 106 females, 15-18 years old; 82% were African-American and 18% Caucasian. RESULTS: Significant correlations between interview and chart were seen for information about menarche, age at first intercourse, number of sexually transmitted diseases (STDs), and number of sexual partners. Accuracy of reporting sexually transmitted infections varied according to the organism; HPV infection was underreported more than other infections. Chart documentation of sexual histories was inadequate. CONCLUSIONS: Adolescents generally provide reliable sexual histories, but health care providers may not be documenting these histories adequately. PMID- 7779836 TI - Identifying adolescent drug users: results of a national survey on adolescent health in Switzerland. AB - OBJECTIVE: To explore the proportion and characteristics of adolescents who use illicit drugs and contrast them with adolescents who do not use such drugs in Switzerland. To facilitate the detection of adolescents with drug related difficulties. METHODS: We used data from a national survey on adolescent health in Switzerland (N = 9,273) conducted in 1992 and 1993. The survey is based on self-administered questionnaires among a representative sample of adolescents enrolled in schools and apprenticeship programs. We used exploratory analysis for identifying characteristics which set the drug user apart from non-users and performed confirmatory multivariate logistic regression analysis to examine which variables remain independently associated with heroin or cocaine use. RESULTS: In Switzerland, 3.1% of adolescents have taken heroin or cocaine at least once in their life, and 27.7% have already used cannabis. Analysis of lifestyles and health of adolescents show that young drug users present difficulties in integrating in society, have health problems and difficulties in relationships, situations which tend to be less common among other adolescents. Yet, they also display marked similarities, most notably in that over 70% had seen a physician in the past year. However, while 40% of the drug users expressed a need for help with drug related problems, only 6% had actually talked about them with a physician. Characteristics that remained independently associated with heroin and cocaine use after controlling for confounding factors were age, sex, nationality, type of education, feelings of suicide, past and present smoking, and use of cannabis. CONCLUSION: The level of illicit drug use among Swiss adolescents is high compared to other European countries but lower than the United States. Drug using adolescents display a constellation of characteristics which should make it possible to identify them and offer help. Yet, even though they may have frequent contact with the health services, their drug problems are generally not recognized by the gatekeepers of the health services and no specific aid is available to them. Drug prevention must be intensified and medical doctors sensitized to the drug problems which adolescents may face. PMID- 7779837 TI - Induction of adhesion molecules on the endothelia of rejecting cardiac allografts. AB - BACKGROUND: Adhesion of leukocytes to vascular endothelium and their migration from the circulation into underlying tissue is regulated by an array of inducible cell adhesion molecules. We determined the kinetics and expression patterns of adhesion molecules expressed by the endothelia of rat cardiac allografts including the following: major histocompatibility complex class II (OX6), intercellular adhesion molecule-1 (1A29), vascular cell adhesion molecule-1 (5F10), leukocyte function-associated antigen-1 alpha-chain (WT.1), the common beta-chain of beta 2 integrins (WT.3), and very late activation antigen-4 (HP2.1) on inflammatory cells. METHODS: Intraabdominal heterotopic cardiac allografts (n = 12) were transplanted from the dark agouti (DA) rats (AG-B4, RT1a) to the Wistar-Furth (WF) rats (AG-B2, RT1v) strain and syngeneic controls (n = 12) were transplanted from dark agouti rat donors to dark agouti rat recipients. The grafts were removed 1, 3, and 5 days after transplantation, and cryostat sections were prepared for indirect immunoperoxidase staining with monoclonal antibodies. The intensity of adhesion molecule expression was scored from 0 to 3 in a blind review. RESULTS: In nontransplanted dark agouti rat hearts, intercellular adhesion molecule-1 was constitutively expressed at a low level on capillary (0.5 +/- 0.5) and postcapillary venular (0.5 +/- 0.2) endothelia. In syngeneic controls, the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was also faint and not induced, but a clear induction of class II expression was found on capillary endothelia. Large vessels stained negative for adhesion molecules. In allografts, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, but not class II, were significantly upregulated on capillary endothelia (p < 0.05). On postcapillary venular endothelia, a distinct induction (p < 0.05) of all three molecules was observed during acute rejection 5 days after transplantation. Concomitantly, the inflammatory leukocytes expressed high levels of leukocyte function-associated antigen-1 alpha-chain and beta-chain in the perivascular space. The expression of very late activation antigen-4 by lymphocytes was, however, nonexistent. In allograft arteries and arterioles, class II and vascular cell adhesion molecule 1, but not intercellular adhesion molecule-1, were weakly expressed during acute rejection. CONCLUSIONS: Our results suggest that postcapillary venular endothelia may be the major site for leukocyte extravasation during acute cardiac allograft rejection in the rat model. PMID- 7779838 TI - Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations. AB - BACKGROUND: The relative importance and interrelationship of risk factors for posttransplantation lymphoproliferative disorder are poorly understood. METHODS: The prospective pretransplantation serologic testing for Epstein-Barr virus of all nonrenal solid organ transplant recipients at our institution made it possible to assess the relative risk for posttransplantation lymphoproliferative disorder in seropositive and seronegative recipients. RESULTS: Fourteen cases of lymphoproliferative disorder were identified in the first 389 consecutive transplant recipients (288 liver, 44 heart, 20 lung, 37 kidney-pancreas) undergoing transplantation from 1985 to 1992 (mean follow-up 33 months). The incidence rates of lymphoproliferative disorder (per 100 person-years) during the first 2 years after transplantation (a period in which all cases occurred) were 1.4 for liver, 2.0 for heart, 6.2 for lung, and 5.2 for kidney-pancreas transplant recipients and were significantly different between liver and lung (p = 0.005) and liver and kidney-pancreas (p = 0.002) groups. Of 367 seropositive patients, lymphoproliferative disorder developed in only three. The incidence rate ratios between seronegative and seropositive recipients were as follows: 76 ([95% confidence interval; 46, 144], p = 0.0000) for any form of lymphoproliferative disorder and 145 ([60, 347], p = 0.0000) for fatal or brain forms. The incidence rate of lymphoproliferative disorder was significantly higher for seronegative recipients who required antilymphocyte antibody therapy for rejection than for those who received none. CONCLUSIONS: The high intrinsic risk for lymphoproliferative disorder in the Epstein-Barr virus seronegative patient, which is amplified by higher levels of immunosuppression, may, in some instances, preclude transplantation. PMID- 7779839 TI - Use of exercise electrocardiography, technetium-99m-MIBI perfusion tomography, and two-dimensional echocardiography for coronary disease surveillance in a low prevalence population of heart transplant recipients. AB - BACKGROUND: Coronary artery disease has been reported to be a significant cause of long-term morbidity and mortality after heart transplantation. However, the diagnosis of coronary disease by means of noninvasive procedures has shown disappointing accuracy, and many centers currently recommend an annual surveillance coronary angiogram. METHODS: We prospectively studied the accuracy and feasibility of a symptom-limited upright bicycle exercise, combined with computerized electrocardiogram analysis, echocardiography, and perfusion scintigraphy in 37 consecutive heart transplant recipients at 2.8 +/- 1.4 years after transplantation for routine follow-up coronary angiography. RESULTS: No patient had any hemodynamically significant (> 50% diameter) coronary stenosis, but luminal irregularities were detectable in four patients. The exercise electrocardiogram was interpretable in only 22 patients (59%), and two of the remaining patients (9%) had false-positive results. The feasibility of perfusion tomography (100%) and two-dimensional echocardiography (97%) were greater than for stress electrocardiogram (p < 0.001 and p < 0.01 respectively). False positive results were obtained at stress echocardiography in one patient (3%), and at scintigraphy in six patients (16%, p = not significant). None of these methods detected coronary artery stenoses of less than 50% diameter. CONCLUSIONS: Both exercise perfusion tomography and two-dimensional echocardiography are feasible and can be used with adequate specificity for the noninvasive diagnosis of coronary artery disease in heart transplant recipients. However further studies are needed to determine their respective sensitivity. PMID- 7779841 TI - Heart transplantation in the United Kingdom: who waits longest and why. AB - BACKGROUND: This study aims to identify characteristics that increase the chance of death of potential cardiac transplant recipients before donor organs become available. METHODS: Between June 1, 1988, and May 31, 1993, 332 patients were accepted for heart transplantation; 235 underwent surgery. Ninety-seven patients had not received transplants; of these, 71 died, 13 were transferred to other lists, and 13 were awaiting organs at the close of the study. Median waiting time for those patients who received organs was 109 days, whereas patients who did not receive organs spent a median of 94 days on the list. Recipients are matched to donor organs according to blood group, size (height), and, recently, preoperative transpulmonary pressure gradient. Recently cytomegalovirus antibody mismatches (positive donor to negative recipient) have been avoided where possible. These factors, together with age, gender, underlying diagnosis, previous heart surgery, and Toxoplasma antibody status were studied to assess their influence on waiting time and survival. RESULTS: No characteristics were found significantly to influence survival after acceptance, so that the chance of death while the patient was waiting for heart transplantation is mainly affected by the severity of disease and the length of time a patient waits. In multivariate analyses the following were independently significantly associated with shorter waiting times: small patients (< 1.7 m tall; p = 0.005), patients with blood types B and AB (p = 0.003), and patients with cardiomyopathy (p < 0.001). CONCLUSIONS: These results can be used by cardiologists to help assess the time at which a patient should be referred for transplantation. PMID- 7779842 TI - Assessment of forced expiratory volume in one second-fraction of the engrafted lung with 133-Xe radiospirometry improves the diagnosis of bronchiolitis obliterans syndrome in single lung transplant recipients. AB - BACKGROUND: Staging of bronchiolitis obliterans syndrome is based on the decline of forced expiratory volume in 1 second, a measure of overall ventilatory capacity. A single staging system is applied to all lung recipients, regardless of the bias which can be caused by the native lung after single lung transplantation. METHODS: We determined the decline of graft function in single lung recipients by a combination of two methods: 133-Xe radiospirometry and dynamic spirometry. The forced expiratory volume in 1 second fraction of the transplant (FEV1tx) was calculated from the proportion of ventilation of the transplant (Vtx) and forced expiratory volume in 1 second. Eight single lung recipients were followed up for a median observation period of 17 months; bronchiolitis obliterans syndrome developed in four of them. RESULTS: The fractional decline of forced expiratory volume in 1 second of the transplant was significantly greater than the decline of forced expiratory volume in 1 second (p = 0.016) in all patients during the follow-up. In the patients with bronchiolitis obliterans syndrome, the mean decline in forced expiratory volume in 1 second was 1.1 L (39.5%), and in forced expiratory volume in 1 second of the transplant it was 0.9 L (55.8%). The measurement of forced expiratory volume in 1 second of the transplant suggested stage 2a and 3a dysfunction in two grafts in which the assessment of forced expiratory volume in 1 second indicated stage 1a bronchiolitis obliterans syndrome. In one patient, decrease of forced expiratory volume in 1 second of the transplant was suggestive of chronic dysfunction 4 months before it was diagnosed by biopsy and declined lung function. CONCLUSIONS: The assessment of forced expiratory volume in 1 second seems to underestimate the severity of chronic dysfunction in single lung grafts. Instead, the determination of forced expiratory volume in 1 second of the transplant with radioactive tracers provides selective information of the graft function, which could be used for clinical evaluation of bronchiolitis obliterans syndrome in single lung recipients. PMID- 7779840 TI - Transcoronary and pulmonary vascular dynamics of endothelin-1 in heart transplant recipients. AB - BACKGROUND: Endothelin-1, a potent endothelium-derived vasoconstrictor peptide, has recently been shown to be elevated in heart transplant recipients and may be a participant in posttransplantation vasculopathy. METHODS: We measured peripheral venous endothelin-1 concentrations in eight heart transplant recipients and eight age- and gender-matched healthy controls. Subsequently, in 21 transplant recipients, right atrial, aortic, and coronary sinus plasma was obtained and endothelin-1 levels were measured. Potential correlations to donor and recipient age, cyclosporine levels, hemodynamic parameters, donor heart ischemic time, time from transplantation, and serum creatinine were examined. In eight more patients, right atrial levels of endothelin-1 were measured before and after endomyocardial biopsy to examine the effect of this procedure on endothelin 1 concentrations. RESULTS: Peripheral endothelin-1 concentrations were significantly higher in heart transplant recipients (45.6 +/- 1.8 versus 25.8 +/- 2.3, p < 0.001). Multiple regression analysis showed a significant correlation between right atrial endothelin-1 and pulmonary artery systolic pressure (r = 0.48), as well as serum creatinine (r = 0.52). No relation to blood pressure, right atrial pressure, pulmonary vascular resistance, recipient age, cyclosporine levels, or donor heart ischemic time was observed. In 11 patients, a 38% +/- 7% fall in endothelin-1 levels across the pulmonary bed was observed, suggesting extraction across the lung in these subjects. Nine patients had net release of endothelin-1 (95% +/- 26% rise) across the coronary vascular bed, whereas 12 patients showed net extraction (24% +/- 4% fall). Endomyocardial biopsy had no influence on endothelin-1 levels (prebiopsy: 48.3 +/- 1.7; postbiopsy: 42.3 +/- 2.34; p = Not significant). CONCLUSION: These findings suggest that endothelin-1 levels in transplant recipients may be influenced by renal function and may contribute to pulmonary hypertension. The significance of transcardiac release of endothelin in some patients is unclear: further studies are needed to determine the pathophysiologic significance of endothelin-1 in heart transplant recipients. PMID- 7779843 TI - Dobutamine thallium 201 perfusion imaging in candidates for lung transplantation. AB - BACKGROUND: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined. METHODS: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization. RESULTS: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload. CONCLUSIONS: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach. PMID- 7779844 TI - Evaluation of ischemic heart disease in potential lung transplant recipients. AB - BACKGROUND: The prevalence of coronary artery disease in potential lung transplant recipients has not been extensively studied. Given the limited donor supply, a high degree of sensitivity for detecting occult disease is essential. METHODS: This retrospective study examined both the clinical indications for coronary angiography and the extent of coronary arteriosclerotic disease in 105 consecutive potential lung transplant candidates. RESULTS: Fifty-one patients (49%) underwent angiography to either exclude asymptomatic atherosclerosis (n = 46) or define the extent of known symptomatic ischemic heart disease (n = 5). The perceived risk of occult disease according to a semiquantitative coronary risk assessment score that included hypertension, hyperlipidemia, diabetes, smoking, a family history of coronary artery disease, and electrocardiographic or echocardiographic abnormalities influenced the decision to perform angiography: 4 of 44 patients (9%) with two or fewer risk factors underwent angiography versus 42 of 56 patients (75%) with more than two risk factors (p < or = 0.05). A higher risk factor score also correlated with angiographic evidence of coronary artery disease. In the 46 patients without symptoms who were studied, two hemodynamically significant but unsuspected coronary lesions were identified. Six other patients without symptoms had noncritical (< 50%) lesions. Among the five patients with angina or a prior myocardial infarction, coronary angiography showed either minimal atherosclerosis (n = 2) or non-life threatening anatomy (n = 3). Angiographic findings did not exclude any patient from transplant listing. CONCLUSION: Coronary angiography appears most useful in patients without symptoms with multiple coronary risk factors and in a subset of patients who might otherwise be excluded from lung transplantation because of a history of symptomatic cardiovascular disease. PMID- 7779845 TI - Acute lung injury in lung allografts. AB - BACKGROUND: Acute alveolar injury is a pathologic description of a nonspecific response of the lung to an acute injury. It has been our experience that acute alveolar injury may be seen in transbronchial biopsy and open lung biopsy specimens from patients who have successfully undergone lung transplantation. Because no studies of the clinical significance of acute alveolar injury in lung transplant recipients are available in the literature, we reviewed the impact of this pathologic finding in patients who underwent transplantation in the Toronto Lung Transplant Program. METHODS: From November 1983 through December 1992, we retrospectively reviewed all transbronchial biopsies and open lung biopsies performed in lung transplant recipients. RESULTS: Of the 137 transplantations performed (53 single and 84 double) acute alveolar injury was observed in 21 single (34 of 173 transbronchial biopsy and 3 of 11 open lung biopsy) lung biopsy) and 22 double (38 of 415 transbronchial biopsy and 3 of 11 open lung biopsy) lung transplantations. We sought to explain this finding on the basis of the concurrent clinical scenario. Acute alveolar injury occurred most commonly in association with infection (52%) followed by postoperative period (19%) and acute (16%) rejection. Acute alveolar injury occurred as an isolated finding in 7% of patients. It occurred within the first 4 months after transplantation in 80% of cases. In 10 of 21 single lung transplantations and 12 of 22 double lung transplantations, acute alveolar injury was seen at least twice. However, no difference was found in mortality between such patients (6 of 10 single and 6 of 12 double lung transplantations) and patients with only one episode of acute alveolar injury. CONCLUSION: Acute alveolar injury is a relatively common finding in histologic specimens from patients with lung transplantation and is most commonly associated with infection. PMID- 7779846 TI - Improved outcome of rat lung transplantation with modification of the nonsuture external cuff technique. AB - BACKGROUND: The development of lung transplantation in inbred rats has simplified immunologic studies concerning lung allografts. Unfortunately, up to now, such models have been limited by the high level of surgical expertise required. METHODS: In this study 92 rats underwent left lung transplantation with a simplified cuff technique. The feasibility and reliability of this technique was determined by examining graft patency through the use of gross and histologic examination, angiography, and bronchography. RESULTS: On gross examination, grafts looked well perfused and ventilated. Histologic examination showed little evidence of foreign body reaction against the Teflon cuff devices, and angiography showed no abnormalities; however, bronchography did show signs of airway stricture at the site of the anastomosis. CONCLUSION: We conclude that the nonsuture external cuff technique with Teflon devices represents a reliable, safe, and fast method for performing orthotopic left lung transplantation in the rat. PMID- 7779847 TI - Pulmonary vasodilatory properties of prostaglandin E1 are blunted after experimental single lung transplantation. AB - BACKGROUND: Pulmonary dysfunction and right heart failure are still a common clinical problem after single lung transplantation. METHODS: In this study we investigated the pulmonary vasodilatory properties of prostaglandin E1 in pigs during the first 4 hours after left lung allotransplantation. With the use of extracorporeal circulation and total right heart bypass, the right and left pulmonary arteries could be individually perfused and the drug effect in each lung separately analyzed either at equal blood pressures or at equal blood flows in the pulmonary arteries. Twelve animals received in a randomized double-blind fashion either saline solution or an increasing prostaglandin E1 infusion (10, 25, 50, and 100 ng/kg/min; 15 minutes each). After a drug-free period of 75 minutes, the infusion schedule with 25, 50, and 100 ng/kg/min was repeated. RESULTS: During the first part of the study the highest dose of prostaglandin E1 decreased the mean systemic arterial pressure by 25%, but an almost similar decrease occurred in the control animals. During the second infusion period a 28% decrease was observed only in the animals treated with prostaglandin E1. None of the infusions was able to decrease pulmonary vascular resistance. Instead prostaglandin E1 diverted two thirds of the pulmonary blood flow toward the native lung, and this diversion manifested itself as an earlier improvement of the arterial oxygen tension in the drug-treated animals. The end-tidal carbon dioxide values measured from each lung corresponded to those from the common expiratory limb of the system, but there was a distinct gradient in the range of 14 to 20 mm Hg between the arterial and end-tidal carbon dioxide values. CONCLUSIONS: We conclude that prostaglandin E1, in doses tolerated by the systemic circulation, is ineffective in the treatment of the increased pulmonary vascular resistance after single lung transplantation. PMID- 7779849 TI - Heterotopic heart transplantation for elevated pulmonary vascular resistance in pediatric patients. AB - BACKGROUND: The presence of significant elevation of pulmonary vascular resistance is a major risk factor for death after orthotopic heart transplantation. The choice of procedure for the pediatric patient remains contentious. METHODS: We report three pediatric patients with pulmonary hypertension and raised pulmonary resistance, including two infants, in whom heterotopic transplantation was performed with smaller donor hearts. The hearts were anastomosed to provide left ventricular support alone because predominant left ventricular failure was present, the pulmonary resistance was expected to fall gradually after surgery, and we wished to avoid the potential problems of a pulmonary conduit associated with growth and possible reoperation. RESULTS: The clinical results have been satisfactory in all three patients, who were well and without symptoms. No pulmonary compromise was observed in the smaller thoracic cavity of the two infants. The transpulmonary gradient fell in all three patients, although this reduction was not immediate. CONCLUSIONS: This technique in carefully selected recipients can allow safer transplantation in pediatric patients with elevated pulmonary resistance, can increase the donor pool by allowing use of smaller hearts and nonideal donors, and may reduce the mortality on the transplant waiting list by providing earlier transplantation. PMID- 7779848 TI - A new flush solution for extended lung preservation. AB - BACKGROUND: The aim of this study was to compare the effect of the most frequently used clinical preservation solution (Euro-Collins, group I) with a newly composed low potassium, glucose- and insulin-containing preservation solution (141 mmol/L sodium, 6.4 mmol/L potassium, 119 mmol/L chloride, 5 mmol/L magnesium, 10 gm/L glucose, 10 gm/L dextrane and 20 U/L insulin) (group II) on postischemic lung function. METHODS: We studied 12 isolated New Zealand White rabbit lungs in a closed circuit model during the first 4 hours of reperfusion after 24 hours of ischemic hypothermic storage. RESULTS: Oxygenation capacity, defined by the difference between the arterial and venous oxygen tension was significantly higher in group II compared with group I after 10 (58.7 +/- 5.8 versus 34.9 +/- 7.5 mm Hg), 30 (63.5 +/- 7.8 versus 27.3 +/- 10.4 mm Hg) and 180 minutes (77.7 +/- 7.2 versus 8.8 +/- 5.6 mm Hg). Ventilatory pressure was significantly lower in group II after 1 minute (11.3 +/- 1.3 mm Hg versus 13.7 +/ 0.5 mm Hg, p < 0.05), with no significant difference thereafter. No significant difference was found in pulmonary vascular resistance except after 20 minutes (30.8 +/- 1.2 dyns/cm5 [group I] versus 27.1 +/- 1.1 dyns/cm5 [group II], p < 0.05). CONCLUSION: These data suggest that this new solution provides superior lung function after 24 hours ischemic time compared with Euro-Collins solution. PMID- 7779850 TI - A valid experimental brain death organ donor model. AB - BACKGROUND: This study was designed to establish a validated canine brain death model. Ten consecutive dogs were studied to investigate the effects of brain death on hemodynamic, metabolic, and hormonal function. METHODS: Brain death was induced by inflation of a subdurally placed balloon and was validated neuropathologically. Functional data and blood samples were collected before and 15, 45, 90, 240, 360, and 420 minutes after the induction of brain death. No inotropic or vasoactive support was given. The results are expressed as mean +/- standard error of the mean. RESULTS: The Cushing reflex occurred in all animals and lasted 13.3 +/- 1.5 minutes. Raised catecholamine levels were documented at 15 minutes, whereas the pituitary gland hormones vasopressin and adrenocorticotrophic hormone decreased significantly after 15 and 45 minutes, respectively. Triiodothyronine, thyroxine, and glucagon decreased significantly from 0.58 +/- 0.05 ng/ml, 2.20 +/- 0.15 micrograms/dl, and 49.7 +/- 9.1 pg/ml to 0.34 +/- 0.03 ng/ml (p < 0.05 versus baseline; paired two-tailed t-test), 1.14 +/ 1.14 micrograms/dl (p < 0.05), and 6.9 +/- 1.4 pg/ml (p < 0.05). Insulin and lactate dehydrogenase showed a moderate increase after brain death. Diabetes insipidus occurred after 45 minutes in nine animals (urine output 13.5 +/- 1.8 ml/kg/hour). Left and right ventricular end-diastolic pressure increased significantly toward the end of all experiments. Cardiac output increased and systemic and pulmonary vascular resistance decreased, but heart rate remained unchanged. CONCLUSION: This simple, reproducible, moderately invasive, and reliable model of brain death in animals assesses donor organ function and preservation. Cushing reflex, hyperdynamic state, catecholamine storm, vasopressin and adrenocorticotropic hormone cessation, total cerebral necrosis, and diabetes insipidus were consistent findings. PMID- 7779851 TI - Does the mode of donor death influence the early outcome of lung transplantation? A review of lung transplantation from donors involved in major trauma. AB - BACKGROUND: Pulmonary dysfunction, often delayed in presentation, is among the sequelae of major trauma. Transplantation of lungs from donors involved in major trauma therefore carries a risk of early graft dysfunction. This study was conducted to assess this risk. METHODS: A retrospective comparison of the outcome from 123 donors (57 donors resulting from major trauma, group T, and 66 donors with nontraumatic origin, group NT) in 125 consecutive technically successful lung or heart-lung transplantations. Variables analyzed included the following: clinical and bacteriologic details of donors and indexes of early graft dysfunction in the recipients. RESULTS: Group T donors were more likely to be younger and male (p < 0.05) and more likely to have had lung ventilation for over 48 hours (p < 0.05) than group NT donors. Microbial contamination of routine donor bronchial lavage (72 of 122, 61%) was no higher in group T (34 of 57, 60%), but, in this group, enteric gram-negative bacilli were more common (30% versus 7%; p < 0.05). Male patients were more likely to receive lungs from group T donors (35 male, 23 female), and female patients were more likely to receive lungs from group NT donors (27 male, 40 female). Mode of donor death did not affect the following indexes of early graft function: length of postoperative ventilation, ratio of arterial oxygen tension to fractional concentration of inspired oxygen at 1 or 24 hours after transplantation, or the incidence of diffuse alveolar damage in lung biopsy specimens at 7 days. Thirty-day mortality (28%) was no higher among recipients of group T lungs, but six recipient deaths were donor-related (donor-transmitted pneumonia in five and donor acquired fat embolism in one case). CONCLUSION: The use of donors involved in major trauma does not increase the risk of early complications after lung transplantation providing their specific characteristics are recognized. PMID- 7779852 TI - Lack of successful reanimation of pig hearts harvested more than 10 minutes after death. AB - BACKGROUND: The aim of this study was to evaluate the viability of arrested pig hearts harvested after animal death. METHODS: Hearts (n = 25) were preserved for 2 hours by cold storage (4 degrees C) with St. Thomas' cardioplegic solution no warm ischemia (0 minutes; control) or 10, 20, 30, or 60 minutes of in situ warm ischemia (animal exsanguination). Hearts were then reperfused for 1 hour with whole blood with an in vitro functional testing system. Left ventricular developed pressure and coronary flow were measured during reperfusion. Energetic compound measurements and histologic analysis were performed on tissue biopsy specimens. RESULTS: After 10- and 20-minute warm ischemia, hearts showed a significant decrease in energetic compounds, a 51% and 73% decreases of left ventricular developed pressure, and 38% and 65% decreases in coronary flow, respectively. After 30 minutes hearts showed irreversible ischemic injury with ultrastructural tissue damage, a large decrease in energetic adenine nucleotide compounds, and an inability to beat more than 15 minutes after reperfusion. CONCLUSION: We conclude that in contrast with other species, pig hearts harvested 10 minutes or more after animal exsanguination fail to be successfully reanimated. PMID- 7779853 TI - Heat shock protein-induced T-lymphocyte propagation from endomyocardial biopsies in heart transplantation. AB - BACKGROUND: Recent studies have shown that heat shock proteins can be recognized by T cells during various immunologically mediated inflammatory processes. Injurious stimuli to cells induce an increased production of heat shock proteins which could lead to their cell surface expression and subsequent recognition by the immune system. We have postulated that allograft infiltrating cells may recognize heat shock proteins, especially during rejection. METHODS: This hypothesis was tested by incubating heart transplant biopsy specimens from 89 heart transplant recipients with soluble Mycobacterium tuberculosis extracts, a source of heat shock proteins or recombinant mycobacterial heat shock protein 65. T cell phenotypes were determined by flow cytometry. RESULTS: Mycobacterium tuberculosis extract can induce lymphocyte propagation from heart transplant biopsy specimens especially during rejection. A highly significant correlation was seen between Mycobacterium tuberculosis extract and interleukin-2-induced lymphocyte growth and an accelerated growth was seen for cultures incubated with Mycobacterium tuberculosis extract + interleukin-2. A second series of experiments has also shown the propagation of lymphocytes induced by recombinant mycobacterial heat shock protein-65. T-cell phenotype analysis of biopsy propagated lymphocytes has shown higher frequencies of CD8 cells in Mycobacterium tuberculosis extract and heat shock protein-65 propagated lymphocytes from early posttransplantation biopsy specimens, whereas, later on, most cultures showed a predominance of CD4 cells. T-cell receptor gamma delta cells were more frequently found in biopsy-derived lymphocyte cultures from long-term survivors, especially after propagation with Mycobacterium tuberculosis extract and heat shock protein 65. These gamma delta cells expressed primarily the delta 1 rather than the gamma 9 phenotype. CONCLUSIONS: These observations provide first evidence for the presence of heat shock protein-reactive lymphocytes in cellular infiltrates of transplants undergoing rejection. PMID- 7779854 TI - Activation of intravascular macrophages within myocardial small vessels is a feature of acute vascular rejection in human heart transplants. AB - BACKGROUND: We investigated the pathogenesis of acute vascular rejection by performing immunofluorescent screening on frozen sections for C1q, C3c, and immunoglobulin M in endomyocardial biopsy specimens from all new heart transplants. METHODS: Immunofluorescence for C4c, C5, immunoglobulin G, and immunoglobulin A was performed on all positive endomyocardial biopsy specimens. Twenty-eight positive endomyocardial biopsy specimens from six patients were identified, and 22 of those were studied with transmission electron microscopy. RESULTS: Endothelial hyperplasia and myocyte necrosis were prominent in the five female patients with positive immunofluorescence. In addition, macrophages with ultrastructural cytologic features of activation were seen filling capillaries and venules in intimate contact with endothelium and exiting those vessels. Activated macrophages were large cells with abundant cytoplasm and ruffled borders and contained numerous lysosomes, rough endoplasmic reticulum, and mitochondria. Intravascular activated macrophages were identified in five of six patients with positive immunofluorescence but were not seen in any of the endomyocardial biopsy specimens with negative immunofluorescence, including multiple examples of moderate (grades 2 to 3B) and severe (grade 4) acute cellular rejection. In the five female patients with activated macrophages, acute vascular rejection recurred multiple times with one fatality. Review of the files showed three additional, similar cases. The one male patient with positive immunofluorescence but without activated macrophages had only a single episode of acute vascular rejection. CONCLUSIONS: Complement and antibodies can activate macrophages, so this finding is not surprising. To the best of our knowledge, this is the first report of the intravascular activation of macrophages, and the first association of this process with acute vascular rejection. Activated macrophages may contribute to myocyte necrosis in acute vascular rejection by compromising blood flow in small vessels. PMID- 7779856 TI - Comparison of myocardial cell injury in acute cellular rejection versus acute vascular rejection in cyclosporine-treated heart transplants. AB - BACKGROUND: Myocyte necrosis has been cited as a key feature in the diagnosis and classification of both moderate and severe acute cellular rejection (International Society for Heart and Lung Transplantation grades 3A to 4). However, our previous work suggests that myocyte necrosis is not a typical feature of cellular rejection. METHODS: To clarify this point and to elucidate differences between cellular rejection and acute vascular rejection, we compared the light and electron microscopic features of 35 consecutive endomyocardial biopsy specimens from six patients with acute vascular rejection diagnosed with positive immunofluorescence, 12 consecutive endomyocardial biopsy specimens from three patients with mixed acute vascular rejection and cellular rejection, and 435 endomyocardial biopsy specimens of International Society for Heart and Lung Transplantation grades 2 to 4 cellular rejection. RESULTS: Endomyocardial biopsy specimens from eight of nine patients with acute vascular rejection and mixed acute vascular rejection/cellular rejection exhibited classic myocyte necrosis as the typical form of myocardial cell injury. Myocyte necrosis was characterized by lysis of the sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cell injury in cellular rejection was reversible. Reversible cellular rejection was characterized by extensive loss of myosin filaments and Z-lines with subsarcolemmal and intracytoplasmic accumulation of Z-band material. Cell swelling, mitochondrial swelling, intramitochondrial densities, and lysis of sarcolemma were not observed. CONCLUSIONS: We conclude that myocyte necrosis is a characteristic feature of acute vascular rejection, whereas reversible myocardial cell injury is characteristic of cellular rejection, including grade 4. Myocyte necrosis is not a feature of cellular rejection. The presence of true myocyte necrosis in endomyocardial biopsy specimens from cyclosporine-treated heart transplants implicates some process other than cellular rejection. Processes producing myocyte necrosis include acute vascular rejection, peritransplantation ischemia, and accelerated atherosclerosis. PMID- 7779855 TI - Intragraft monitoring of rejection after prophylactic treatment with monoclonal anti-interleukin-2 receptor antibody (BT563) in heart transplant recipients. AB - BACKGROUND: Anti-interleukin-2 receptor monoclonal antibodies have been used successfully in the prevention of rejection in cardiac allografts in several animal models. METHODS: In an open randomized study murine monoclonal CD3 antibody and BT563, a murine anti-interleukin-2 receptor monoclonal antibody, were given as rejection prophylaxis during the first week after heart transplantation. Cyclosporine therapy was initiated at the third postoperative day. RESULTS: In half the BT563-treated patients an early rejection was histologically shown at week 1, whereas heart transplant recipients treated with murine monoclonal CD3 antibody had a rejection incidence at week 1 of only 9%. During BT563 treatment CD25-positive cells (i.e., cells bearing the interleukin-2 receptor) were not detectable in peripheral blood. However, immunohistologic studies of endomyocardial biopsy specimens taken 1 week after transplantation showed the presence of CD25-positive cells within these specimens in 8 of 10 (80%) of patients with rejection. In patients without rejection CD25-positive cells were present in the biopsy specimens of only two of nine patients (22%). Reverse-transcriptase polymerase chain reaction studies on biopsy material showed the presence of messenger RNA for the interleukin-2 receptor in all and for interleukin-2 in three of five (60%) of biopsy specimens of rejecting grafts. CONCLUSIONS: Although CD25-positive cells were not detectable in peripheral blood during BT563 treatment, these cells were at the same time found to be present within 80% of the endomyocardial biopsy specimens from the rejecting grafts. By initiating cyclosporine treatment at day 0, the synergistic effect of combining cyclosporine and anti-interleukin-2 receptor monoclonal antibodies may result in a lower rejection incidence. PMID- 7779857 TI - Factors affecting the integrity of latissimus dorsi muscle grafts: implications for cardiac assistance from skeletal muscle. AB - BACKGROUND: Severe latissimus dorsi muscle damage may compromise cardiomyoplasty performance. We analyzed factors underlying the damage produced in 20 sheep latissimus dorsi muscles by isolating the influences of electrical stimulation, mobilization (with some loss of vascular supply), loss of normal resting tension, or a combination of these. METHODS: In group I (n = 3), the muscle was mobilized except for its neurovascular pedicle and reattached at normal resting length. In group II (n = 3), the muscle was mobilized and reattached at about 80% of resting length. Groups III (n = 6) and IV (n = 4) were as groups I and II except that continuous indirect stimulation at 2 Hz was added after 2 weeks. In group V (n = 4), the undisturbed muscle received stimulation alone. After 10 to 12 weeks, muscle samples were taken for morphometric analysis. RESULTS: Loss of resting muscle tension appeared to be the single most damaging intervention, though mobilization and stimulation had further deleterious effects. The worst damage was seen when all three factors were combined, when 60% of the muscle cross section was occupied by connective tissue and fat. The changes were significantly more severe in the distal than in the proximal part of the muscle, implicating ischemia as a contributory factor. CONCLUSIONS: Fiber damage reduces the effectiveness of muscle grafts used for cardiac assistance and merits further systematic investigation. PMID- 7779859 TI - Changes in health-related quality of life and depression in heart transplant recipients. AB - BACKGROUND: The intent of this study was to measure health-related quality of life and depression in 94 heart transplant recipients. METHODS: Changes in health related quality of life and depression were examined by administering the Sickness Impact Profile and the Beck Depression Inventory before heart transplantation, as well as 4, 8, 12, 24, 36, 48, and 60 months after surgery. RESULTS: Sickness Impact Profile scores obtained before heart transplantation highlighted the greatest health-related quality of life dysfunction in work, sleep and rest, home management, and recreation and pastimes. Posttransplantation measures suggested improvement (p < 0.05) in emotional behavior, home management, mobility, ambulation, depression, eating behavior, social interaction, body care and movement, sleep and rest, recreation and pastimes, depression, and physical, overall, and psychosocial functioning. Continued improvement was noted up to 5 years after transplantation although patients continued to have marked work related dysfunction. Age, medication regimen, rejection episodes, and a variety of preoperative medical variables were not related to health-related quality of life. Actuarial survival rates at 1, 2, 3, 4, and 5 years were 89%, 87%, 80%, 79%, and 79%, respectively. CONCLUSIONS: Our results suggest that as early as 4 months after heart transplantation, patients show excellent functioning in most health-related quality of life areas. Survival rates are encouraging. Patients did not generally experience problems with depression within the first 4 months after heart transplantation. Notable problems remain after transplantation in rate of return to work where only 53% returned to work by 5 years after heart transplantation. PMID- 7779858 TI - Heart transplantation charges: status 1 versus status 2 patients. AB - BACKGROUND: The current health care environment mandates closer scrutiny of health care dollar allocation. To better understand the distribution of heart transplantation costs, we reviewed hospital and physician billing of patients who underwent orthotopic heart transplantation between August 1988 and September 1993. METHODS: This study is a retrospective review of 107 consecutive cases. Charges and clinical results of United Network for Organ Sharing status 1 patients (n = 46), including 17 bridge to transplantation patients, were compared with those of United Network for Organ Sharing status 2 patients (n = 57). Charges were converted to 1992 dollars. RESULTS: During the first 12 months of the study, 77% of heart transplantations were performed in United Network for Organ Sharing status 2 patients, whereas over the last 12-month period, 25% of the transplantations were performed in status 2 patients. No significant differences were found in age, gender, type of cardiomyopathy, or survival between the status 1 and status 2 groups. The length of hospitalization for the status 1 group ranged from 8 to 138 days (mean 49 days) as opposed to 5 to 82 days (mean 17.5 days) for the status 2 group (p < 0.0001). Pretransplantation hospital charges were significantly higher for the status 1 group ($47,917 to $341,215, mean $109,116) when compared with status 2 ($0 to $10,035, mean $250) (p < 0.0001). No significant difference was found in posttransplantation hospital charges between status 1 ($47,917 to $210,027, mean $95,379) and status 2 patients ($48,093 to $380,745, mean $102,265). Total charges were significantly higher (p < 0.0001) for the status 1 group ($89,910 to $512,331, mean $239,375) when compared with the status 2 group ($63,885 to $455,680, mean $128,594). Total transplantation charges for the study period were $18,341,108. This amount could have paid for 77 status 1 transplantations or 143 status 2 transplantations. CONCLUSIONS: If current trends continue and the donor pool remains the same, most transplant recipients will be status 1, resulting in a comparable number of transplantations performed at twice the charges. PMID- 7779860 TI - Experience with heart transplantation for cardiac tumors. AB - BACKGROUND: Primary cardiac tumors are rare clinical entities. Benign tumors are often amenable to surgical excision, whereas malignant tumors are seldom resectable. Five patients have been reported to undergo orthotopic heart transplantation for inoperable primary cardiac tumors. We review the clinical course of these five patients and present our institutional experience with three patients who underwent orthotopic heart transplantation as primary therapy for unresectable cardiac tumors. METHODS: Retrospective chart review and telephone interview, when possible, were used to gather historical and clinical course data. RESULTS: Of the eight patients who underwent orthotopic heart transplantation for primary cardiac neoplasms, four had malignant tumors (three sarcomas, one lymphoma) and four had locally invasive neoplasms (three fibromas, one pheochromocytoma). For those patients in whom cardiectomy resulted in surgical margins free of tumor (six of eight), orthotopic heart transplantation provided long-term survival (range 14 to 78 months) without tumor recurrence despite therapeutic immunosuppression. The only death in this group, at 6.2 years after operation, was unrelated to tumor recurrence. The patients with tumor identified at the surgical margins died of metastatic disease at 14 and 15 months after the operation in spite of adjuvant chemotherapy. CONCLUSIONS: An awareness by clinicians of the presenting clinical picture of these tumors is warranted in view of the potential for cure by resection or transplantation. Patients with benign primary cardiac tumors appear to benefit from the complete resection afforded by cardiectomy and transplantation. The role of transplantation for patients with malignant tumors remains unclear. Additional studies and continued follow-up with serial echocardiography is necessary to further ascertain the role of heart transplantation in the management of patients with primary cardiac tumors. PMID- 7779861 TI - Potential mechanism of vasomotor dysregulation after lung transplantation for primary pulmonary hypertension. AB - BACKGROUND: Vasomotor regulation in the lung is controlled by a dynamic balance between humoral factors and autonomic innervation. Lung transplantation is a unique clinical situation in which vasoregulation is dependent on humoral factors alone. METHODS: We illustrate the problem of vasomotor dysregulation with a lung transplant recipient in whom life-threatening hypoxemia was dramatically reversed with the administration of organic nitrates. The potential mechanism for this dysregulation was explored by exposing human endothelial cells to hypoxic conditions in vitro and analyzing the cells for the expression of pulmonary vasoconstrictor gene transcripts. RESULTS: The hypoxic microenvironment induced a tenfold increase in the transcription of the pulmonary vasoconstrictor genes endothelin-1 and platelet-derived growth factor within 24 hours. The addition of organic nitrates had a dramatic effect on decreasing the levels of vasoconstrictor transcripts within 30 minutes of exposure. CONCLUSION: These findings suggest that a potential mechanism for the clinical effect of organic nitrates is the inhibition of vasoconstrictor synthesis by hypoxic endothelium. PMID- 7779862 TI - Giant cell myocarditis. AB - BACKGROUND: Giant cell myocarditis is a rare and frequently fatal disorder of unknown origin that is defined histopathologically as diffuse myocardial necrosis with multinucleated giant cells in the absence of sarcoidlike granulomata. The clinical and pathologic features of lymphocytic myocarditis have been described in several recent publications, but the features of idiopathic giant cell myocarditis have not been adequately addressed. METHODS AND RESULTS: We describe five patients with idiopathic giant cell myocarditis who were seen at Stanford University over the past 10 years. In each case the onset was subacute congestive heart failure. After diagnosis each patient received immunosuppressive therapy and was evaluated for heart transplantation. Progressive heart failure and ventricular arrhythmias developed in all. Three died rapidly, two of progressive heart failure and one of sudden cause. Two patients underwent orthotopic heart transplantation and are currently alive, one with disease recurrence. Pathologic studies, including endomyocardial biopsy and evaluation of postmortem or explanted material at transplantation were reviewed. The pathologic studies provided additional support that the giant cells derive from a monocytic/histiocytic lineage. Segmental wall motion abnormalities suggest giant cell myocarditis can be a focal, as well as diffuse process at certain stages of its course. This experience is compared with published cases and implications for diagnosis and treatment are discussed. CONCLUSIONS: In view of the uniformly fatal nature of the disease, heart transplantation should be a serious consideration, and the patients evaluated once the diagnosis is established. Triple-drug immunosuppressive therapy should be considered at the time of diagnosis. PMID- 7779863 TI - Pulmonary amyloidosis occurring after heart transplantation for amyloid heart disease. PMID- 7779864 TI - Modulation by GM1 ganglioside of beta 1-adrenergic receptor-induced cyclic AMP formation in Sf9 cells. AB - The effect of ganglioside GM1 on isoproterenol-induced cAMP accumulation was studied in insect Sf9 cells expressing the human beta 1-adrenergic receptor by infection with recombinant baculovirus. When such Sf9 cells were treated with isoproterenol plus IBMX, intracellular cAMP formation increased approximately 10 fold over the basal level. Preincubation of the baculovirus-infected cells with GM1 for 1 h caused a concentration-dependent inhibition of the isoproterenol induced cAMP accumulation. Phosphatidylserine, GM3, GT1b and a bovine brain ganglioside preparation lacking GM1 did not cause significant inhibition. Forskolin-induced cAMP accumulation was not affected by the GM1 treatment. Inhibition of isoproterenol-induced cAMP formation by GM1 was not observed in Sf9 cells expressing beta 2-adrenergic receptor instead of the beta 1-adrenergic receptor. Binding studies with (-)-[3H]CGP12177 showed that preincubation with GM1 significantly reduced the affinity of antagonist binding to the beta 1 adrenergic receptor. These results suggest that GM1 or related ganglioside structure(s) may function as natural modulator(s) of the beta 1-adrenergic receptor. PMID- 7779866 TI - Selenoperoxidase-dependent glutathione cycle activity in peroxide-challenged leukemia cells. AB - Murine leukemia L1210 cells rendered deficient in glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) by Se deprivation (L.Se(-) cells) were found to be more sensitive to tert-butyl hydroperoxide (t BuOOH) cytotoxicity than Se-replete controls (L.Se(+) cells). Human K562 cells, which express PHGPX, but not GPX, were also more sensitive to t-BuOOH in the Se deficient (K.Se(-)) than Se-satisfied (K.Se(+)) condition. In examining the metabolic basis for selenoperoxidase-dependent resistance, we found that glucose replete Se(-) cells reduce t-BuOOH to t-butanol far more slowly than Se(+) cells, the ratio of the first-order rate constants approximating that of the GPX activities (L1210 cells) or PHGPX activities (K562 cells). Monitoring peroxide induced changes in GSH and GSSG gave consistent results; e.g., glucose-depleted L.Se(+) cells exhibited a first order loss of GSH that was substantially faster than that of glucose-depleted L.Se(-) cells. Under the conditions used, peroxide induced conversion of GSH to GSSG could be stoichiometrically reversed by resupplying D-glucose, indicating that no significant lysis or GSSG efflux and/or interchange had taken place. The apparent first-order rate constant for GSH decay increased progressively for L1210 cells expressing a range of GPX activities from approximately 5% to 100%, demonstrating that peroxide detoxification is strictly dependent on enzyme content. The initial rate of 14CO2 release from D-[1 14C]glucose supplied in the medium was much greater for L.Se(+) or K.Se(+) cells than for their respective Se(-) counterparts, consistent with greater hexose monophosphate shunt activity in the former. These results highlight the importance of selenoperoxidase action in the glutathione cycle as a means by which tumor cells cope with hydroperoxide stress. PMID- 7779865 TI - The effects of terbium on the accumulation of cisplatin in human ovarian cancer cells. AB - In this investigation, we report a relationship between the terbium (Tb3+) binding protein and the accumulation of cisplatin in human ovarian cancer cells. The number of Tb3+ binding sites in cisplatin-resistant C13+ cells is significantly greater by 79% than those in cisplatin-sensitive 2008 cells. Exposure to Tb3+ also increased the cellular accumulation of cisplatin. The accumulation of cisplatin as a function of the Tb3+ concentration in the C13+ cells (0.85%/microM Tb3+) was significantly greater than the accumulation of cisplatin in 2008 cells with respect to Tb3+ (0.46%/microM Tb3+). The number of Tb3+ binding sites in revertant RH4 cells was similar to that in 2008 cells. The RH4 cells were less sensitive to the stimulatory effects of Tb3+ than the C13+ cells. Our results show that the Tb3+ binding protein correlates with cisplatin resistance, and the receptor binding of Tb3+ increases the accumulation of cisplatin in cisplatin-resistant cells. PMID- 7779867 TI - Reaction of nitric oxide and its derivatives with sulfites: a possible role in sulfite toxicity. AB - The reaction between sulfites and nitric oxide or proposed carriers of nitric oxide (nitrosylated bovine serum albumin and S-nitrosoglutathione) was investigated as a potential source of the adverse effects of sulfites on biological systems. Rapid reaction occurred between sulfites and all of these reagents. Also, the ability of nitric oxide and these carriers of nitric oxide to inhibit platelet aggregation was reversed by low concentrations of sulfites. Counteraction of nitric oxide's ability to function in cell signaling processes may be a major cause of sulfite toxicity. PMID- 7779868 TI - Protein kinase C isoforms in muscle cells and their regulation by phorbol ester and calpain. AB - Objectives were to identify the PKC isoforms in cultured muscle cells, to examine roles of Ca(2+)-dependent proteinases (calpains) in processing of various muscle PKC isozymes and to obtain a mechanistic description of the processing of PKCs by examining the temporal relationships between phorbol ester-dependent translocation of muscle PKCs and calpains between cytosolic and membrane compartments. Using six isoform (alpha, beta, gamma, delta, epsilon, zeta) specific polyclonal antibodies, PKC alpha, delta and zeta were detected in rat skeletal muscle and in L8 myoblasts and myotubes. PKC alpha and zeta were primarily localized in the cytosolic fraction of L8 myotubes whereas PKC delta was more abundant in the membrane fraction. Phorbol ester (TPA) caused rapid depletion of myotube PKC alpha and PKC alpha and PKC delta isoforms from the cytosolic compartment and rapid appearance of these isoforms in the membrane fraction. However, long-term exposure of myotubes to TPA eventually caused down regulation of PKCs in the membrane compartment. Down-regulation of PKCs in the membrane fraction was partially blocked by calpain inhibitor II. However, the rapid TPA-dependent cytosolic depletion of PKCs was unaffected by calpain inhibitor. This suggests that calpains may be responsible for membrane-associated down-regulation of PKCs but not for cytosolic depletion. In the final study we assessed the effects of phorbol ester on compartmentation of m-calpain with PKCs in muscle cells. Like the PKCs, TPA caused rapid association of m-calpain with the membrane fraction followed by down-regulation. This demonstrates that phorbol esters cause translocation of both PKCs and calpains to membranes where processing of PKCs may occur via the limited proteolysis exerted by calpains. PMID- 7779869 TI - Modulated glycosylation of proteoglycans during differentiation of human B lymphocytes. AB - Proteoglycans are mediators of cellular adhesion and regulate growth factor activities. Proteoglycans of B lymphocytes undergo structural changes during B cell ontogeny which may correspond to the specific requirements of the respective microenvironment of the maturing cell. We analyzed three human B cell lines representing pre-B cells (Nalm-6), activated B cells (Jok-1) and plasma cells (U266) for their cellular proteoglycans. Gel filtration of the 35S-labeled macromolecules of the three cell lines revealed an increase in size in the order Nalm-6 < Jok-1 < U266. In Jok-1 and U266 cells the major pool of proteoglycans consisted of proteochondroitin sulfates of 50 to 90 kDa. These proteolglycans carried a protein core of approx. 30 kDa to which 1 to 3 glycosaminoglycan chains in the range of 28 to 32 kDa were attached. In Nalm-6 cells only free chondroitin sulfate chains of 23 kDa, but no intact proteoglycans, were detected. Chondroitin sulfate chains were predominantly composed of chondroitin-4-sulfate, those of Nalm-6 and U266 cells additionally contained 10-20% of unsulfated disaccharides. In U266 cells 30% of glycosaminoglycans consisted of heparan sulfate either bound to pure proteoheparan sulfate or to chondroitin sulfate/heparan sulfate hybrid proteoglycans. Earlier, syndecan-1 was described as a hybrid proteoglycan containing heparan sulfate/chondroitin sulfate chains which is transcribed by murine B cells at early and late maturation stages. In order to see whether syndecan is transcribed by the human B cell lines used here, we measured expression of syndecan mRNA by the reverse transcriptase polymerase chain reaction. Similar to murine lymphocytes, syndecan-specific mRNA was detected in Nalm-6 and U266 cells, equivalent to early and late B cells, but not in lymphoblastoid Jok-1 cells. However, Nalm-6 cells do not produce proteoheparan sulfate. In these cells, syndecan synthesis may be blocked at the translational level. Also, the proteoglycans of U266 are different from syndecan-1 in their composition of glycosaminoglycans and in size of protein cores. Together, these results indicate that the major pool of proteoglycans produced by human B cells consists of proteochondroitin sulfate and additionally in later stages of a smaller proportion of proteoheparan sulfate which is not identical to syndecan-1. During distinct phases of B cell differentiation, modulations in the glycosaminoglycan moiety concerning size and sulfation of glycosaminoglycan chains were also found. PMID- 7779870 TI - [Louis Pasteur at the 100th anniversary of his death]. PMID- 7779871 TI - [Puerperal endometritis: study of 52 clinically and microbiologically diagnosed cases]. AB - BACKGROUND: To know the epidemiologic features, clinical manifestations and etiology of puerperal endometritis in our environment in addition to the use of endometrial cultures in the microbiologic diagnosis of this infection. METHODS: A retrospective study of 52 cases of puerperal endometritis, clinically and microbiologically diagnosed over a 4-year period. RESULTS: Fifty percent of patients had undergone a cesarean, 36.5% presented puerperal anemia and 23% presented upper amniorrhexis at 12 hours. All the patients presented puerperal fever greater than 38 degrees C, 46% uterine subinvolution and 24% fetid lochia. The most frequently isolated microorganisms in the endometrial aspirate were Escherichia coli, Streptococcus agalactiae and Bacteroides spp. The association of ampicillin plus cefoxitine and clindamycin plus tobramycin presented in vitro efficacy in more than 85% of the isolates. CONCLUSIONS: The practice of endometrial aspirate and blood cultures in patients suspected of having puerperal endometritis effectively contributes to the diagnosis and treatment of this infection. PMID- 7779872 TI - [Assessment of the sensitivity to antifungal agents of clinical isolates of Candida albicans serotype A and B by the ATB Fungus method]. AB - BACKGROUND: Candida albicans is the most frequently species isolated in patients with candidiasis. This species may be antigenically divided in serotypes A and B, which have a different pathogenic behavior and antifungal susceptibility pattern. METHODS: The antifungal susceptibility of 443 clinical isolates from both serotypes of C. albicans to 5-fluorocytosine (5FC), amphotericin B, nystatin, econazole, miconazole and ketoconazole has been tested by means of the ATB Fungus method. RESULTS: Both serotypes showed a similar in vitro susceptibility to amphotericin B, nystatin, econazole, miconazole and ketoconazole. All the isolates were susceptible to amphotericin B and nystatin. A small number of in vitro resistant isolates were observed to azole compounds. However, serotype B was significantly more resistant than serotype A (p = 0.0001) to 5FC. CONCLUSIONS: C. albicans serotype B shows a lower susceptibility than serotype A to 5FC, an antifungal product not marketed in Spain. Serotyping of C. albicans does not offer additional information on antifungal susceptibility of clinical isolates from this species. PMID- 7779873 TI - [Use of+Rambach agar for the detection of Salmonella in feces using broth enrichment. Comparison with our methodology]. AB - BACKGROUND: A comparative study between Rambach agar and our previously published methodology (Salmonella-Shigella agar + C8-esterase test) was carried out to isolate Salmonella from 815 stools samples after enrichment in selenite broth. METHODS: On Rambach agar all pink and colourless colonies which were oxidase negative and red colonies were also identified. On SS agar, black colonies and colourless colonies which were oxidase negative and C8-esterase test positive were identified biochemically. RESULTS: One hundred and twenty-three colourless, 81 pink and 112 red colonies grown in Rambach agar, and they were subcultured in Kliger agar yielding 7, 2 and 109 Salmonella, respectively. From SS agar, the 113 black and 10 colourless colonies which had previously been positive in the C8 esterase test and oxidase-negative, yielded 113 Salmonella strains (111 and 2, respectively). CONCLUSIONS: Rambach agar is an excellent media for isolating Salmonella after enrichment in selenite broth. If all colourless and pink colonies are further investigated the number of isolates will increase although the workload will increase, too. Therefore, it would be interesting to study a combination of C8-esterase and Rambach agar since it could reduce the workload. PMID- 7779874 TI - [Rickettsia slovaca: an agent of the group of exanthematous fevers, in Portugal]. AB - BACKGROUND: Identification of Rickettsia isolated from Dermacentor marginatus ticks from Portugal. METHODS: Using recently developed techniques (shell-vial isolation, PCR/RFLP genetical methods, SDS-PAGE), serological studies and animal induced pathology to isolate and characterize tick-borne rickettsiae. RESULTS: A total of 632 adults D. marginatus ticks were captured. From the collected ticks, we isolated 18 Rickettsia strains and the results confirm that the isolates from the haemolymph were identical to R. slovaca reference strain. CONCLUSIONS: Dermacentor marginatus ticks infected with Rickettsia slovaca were found in Portugal. This occurrence extended the known, geographical area for this microorganism. It is also a factor that could alter the seroprevalence rates of butonneuse fever. The pathogenicity of this Rickettsia should be evaluated to determine its responsibility for diseases other than butonneuse fever. PMID- 7779875 TI - [Spontaneous mononucleosis caused by cytomegalovirus in the immunocompetent adult]. AB - BACKGROUND: The first Spanish series of spontaneous infectious mononucleosis (IM) by cytomegalovirus (CMV) in immunocompetent adults is reported. METHODS: Patients whose clinical manifestations, physical exam, analysis and serology were compatible with acute CMV infection from 1984 to 1993 were retrospectively reviewed. RESULTS: Thirty patients with a mean age of 36 years fulfilled the diagnostic criteria. All presented fever, alone or associated with other symptoms, with a mean duration of 18 days, which persisted over 3 weeks in 36%. Physical exam showed lymph node enlargement (50%), hepatomegaly (33%), splenomegaly (20%) and was normal in 8 patients (26%). Mean leukocyte count was 9.75 x 10(9) (+/- 4.63 x 10(9) with more than 50% lymphomonocytic cells in 22 patients (76%) and reactive lymphocytes, principally from the outset, although this was observed on days 2 and 60 in 11 cases (36%). LDH, ASAT and ALAT were moderately elevated and ESR was normal. Serologic diagnosis was established from IgM (13%) seroconversion or positive IgM in the two samples with IgG four-fold increase (23%), as well as the presence of positive IgM and invariable high IgG in both determinations (26%) or all IgM positive titers in a single sample (36%). CONCLUSIONS: Infectious mononucleosis by cytomegalovirus is an infrequently diagnosed disease which should be considered in any young patient with fever despite a little demonstrative initial physical exam absence of atypical lymphocytes or a lack of diagnostic serology. PMID- 7779876 TI - [Comparative study of 2 technics for the diagnosis of invasive candidiasis]. AB - BACKGROUND: We evaluate test for the detection of antibodies against-Candida albicans by indirect immunofluorescence (Candida Spot-IF, BioMerieux, Lyon, France and a test developed in our laboratory to detect anti-germ tube antibodies) comparatively for the serodiagnosis of invasive candidiasis. METHODS: A total of 121 sera from 62 patients were studied retrospectively. They were divided into two groups: group I included 71 sera from 28 patients with invasive candidiasis and group II, used as control, included 50 sera from 34 patients with non-invasive candidiasis or without evidence of infection by Candida. RESULTS: Eighty-two percent of group I samples presented anti-germ tube antibodies and 57% of the patients in this group were positive by the Candida Spot-IF test. Both techniques were negative in 5 patients. Five patients in group II showed false positive results by Candida Spot-IF and two of them presented anti-germ tube antibodies also. Both techniques presented a poor correlation (R2 = 0.159; p < 0.001). Detection of anti-germ tube antibodies showed a sensitivity of 82% and a specificity of 94% and Candida Spot-IF showed a sensitivity of 57% and a specificity of 85%. Detection of anti-germ tube antibodies in immunocompetent patients showed a sensitivity of 90% but it decreased to 62% in immunocompromised patients. With the Candida Spot-IF test the sensitivity was 70 and 25%, respectively. CONCLUSIONS: The detection of anti-germ tube antibodies was more sensitive and specific than detection of antibodies by the Candida Spot-IF test and it can be used for the serodiagnosis and follow up of patients with invasive candidiasis. PMID- 7779877 TI - [Virulence factors and 0 serogroups of Escherichia coli as a cause of community acquired urinary infections]. AB - BACKGROUND: The aim of this study was to determine the virulence factors and 0 serogroups of E. coli strains that cause community acquired urinary tract infections (UTI). METHODS: We examined 103 E. coli strains isolated from the urine of patients with UTI. The following virulence factors were investigated using phenotypic techniques: the alpha-haemolysin (Hly), the cytotoxic necrotizing factor type 1 (CNF-1) and the mannose-resistant haemagglutination (MRHA) types III, IVa and IVb expressed by P fimbriated E. coli. Serotyping of 0 antigen was carried out by means of a microtechnique using 163 antisera. RESULTS: Fifty-five (53%) of the 103 E. coli strains examined showed some of the virulence factors investigated in this study; 41% of the strains were Hly+, 28% were CNF-1+ and 48% expressed MRHA types III, IVa or IVb. The uropathogenic strains characterized belonged to 27 different 0 serogroups. However, 68% were from one of 10 serogroups (01, 02, 04, 06, 09, 018, 027, 073, 075 and 077) and 36% were from one of only 3 serogroups (02, 04 and 06). Furthermore, the virulence factors were concentrated in strains belonging to the 3 serogroups most frequently detected. Thus, 36 (97%) of the 37 strains of these 3 serogroups showed virulence factors, versus only 19 (29%) of 66 belonging to other serogroups (p < 0.001). CONCLUSIONS: Our results support the special pathogenicity theory and suggest that many cases of community acquired UTI may be caused by a limited number of uropathogenic E. coli strains that produce toxins (Hly+ and/or CNF-1+) and possess P fimbriae or P-related adhesins (with MRHA types III, IVa or IVb), and that usually belong to 02, 04 and 06 serogroups. PMID- 7779878 TI - [Ocular toxocariasis or retinoblastoma?]. AB - BACKGROUND: Seroprevalence studies in Spain have shown that a high number of the population has been in contact with Toxocara canis although no cases of ocular involvement by this helminth have been described. The clinical and age of presentation makes differential diagnosis with retinoblastoma necessary, which is at time difficult, although essential since the treatment and prognosis are very different. METHODS: One case of ocular toxocariosis and the diagnostic keys based on the following are described: ophthalmologic exploration, imaging techniques (ECHO, TC, NMR), aqueous humor cytology, LDH quotient of aqueous/serum humor, and determination of specific anti-Toxocara antibodies by ELISA in serum and aqueous humor. CONCLUSIONS: Correct differential diagnosis between ocular toxocariosis and retinoblastoma is required. PMID- 7779879 TI - [The 8th cholera pandemic: Vibrio cholerae serogroup 0139 (Bengala strain)]. PMID- 7779880 TI - [Criteria for antibacterial susceptibility in vitro. Ampicillin as an example]. PMID- 7779881 TI - [Axillary suppurative adenitis in an HIV-positive patient]. PMID- 7779882 TI - [Ungual dystrophy, erythemo-desquamative and nodular lesions in the legs of a patient with trisomy 21]. PMID- 7779884 TI - [Ceftibuten]. PMID- 7779883 TI - [Which of the 2 patients has osteomyelitis?]. PMID- 7779885 TI - [Endocarditis and renal abscess caused by Gemella morbillorum]. PMID- 7779886 TI - [Conjunctivitis caused by Capnocytophaga ochracea in a 2-year-old girl]. PMID- 7779887 TI - [Human ehrlichiosis in Spain. Various epidemiologic considerations]. PMID- 7779888 TI - [Nosocomial pneumonia caused by Neisseria meningitidis. Diagnosis by aspiration transthoracic puncture]. PMID- 7779889 TI - [Acute bronchiolitis and oral vaccination with attenuated poliovirus]. PMID- 7779890 TI - [Visceral leishmaniasis and AIDS: detection of Leishmania infantum antibodies with western blot]. PMID- 7779891 TI - [Streptococcus group A: new faces of an old know]. PMID- 7779893 TI - [Evaluation of the E test method in the antimicrobial sensitivity of Neisseria meningitidis to penicillin]. AB - BACKGROUND: The E test (AB Biodisk, Solna, Sweden) is a rather new method for performing antimicrobial susceptibility test--their results are generated directly as MICs. Due to its simplicity, is available in nearly all laboratories. The present study evaluates the effectiveness of the E test for susceptibility studies of Neisseria meningitidis to penicilline. METHODS: The MICs of penicilline of 55 strains of Neisseria meningitidis, studied by E test and by microdilution method, were compared to those obtained by agar dilution using both Mueller-Hinton (MH) and Mueller-Hinton with a 5% of sheep blood (MH+S) as test culture bases. RESULTS: The concordance rate (+/- 1 log2 of dilutions) was 100% in all cases, except for the E test on MH+S which yielded a 98.2% value. The Pearson's correlation coefficients were 0.95 and 0.84 for the E test and 0.88 and 0.85 for microdilution, using MH and MH+S. Roughly 70% of strains were considered susceptible to penicillin using MH for the in vitro tests, whereas only 40% of them were so considered using MH+S. CONCLUSIONS: The E test can be considered a good alternative to agar dilution method when testing susceptibility of N. meningitidis to penicilline, and MH is the best culture base for these assays. PMID- 7779892 TI - [Resistance to imipenem in Enterobacter aerogenes]. AB - BACKGROUND: In June, 1993, an Enterobacter aerogenes strain was isolated in the Hospital de la Creu Roja from Hospitalet de Llobregat (Barcelona), which was resistant against all beta-lactams, including imipenem. Since is unusual in Enterobacter sp. to isolate imipenem resistant strains, we decided to study its resistance mechanism. METHODS: To study the E. aerogenes 174004/H resistance mechanism beta-lactamase isoelectrofocalization was performed together with the determination of kinetic constants in order to characterize the beta-lactamase, and a polyacrylamide gel electrophoresis in order to observe the profile. RESULTS: The strain of E. aerogenes 174004/H exhibits a chromosomic beta lactamase with a pI higher than 9.2 and a decrease in an outer membrane protein of 42 kDa, probably a porine. CONCLUSIONS: E. aerogenes 174004/H resistance against imipenem is due to an hyperproduction of a chromosomic beta-lactamase with a pI higher than 9.2 and to a 42 kDa decrease of an outer membrane protein expression. PMID- 7779894 TI - [Evaluation of specificity of pneumococcal antigen detection in clinical samples by using the polymerase chain reaction as reference method]. AB - BACKGROUND: Sensitivity and specificity of latex agglutination test on samples obtained by transthoracic needle aspiration was evaluated for diagnosis of pneumococcal pneumonia by using the polymerase chain reaction as reference method. METHODS: Samples from 29 patients with community acquired pneumonia were processed for culture, antigen detection and polymerase chain reaction. The latex agglutination test was performed with a reagents kit (Slidex meningite kit, BioMerieux, France) using the procedure recommended by the manufacturer. The polymerase chain reaction was carried out by using two primers: Pn2x up and Pn2x down that amplify the PBP2x gene of Streptococcus pneumoniae. RESULTS: Culture was positive in 5 patients, antigen detection in 15 and polymerase chain reaction in 14 patients. The specificity of latex agglutination test was 93% compared with polymerase chain reaction as reference method. CONCLUSION: The pneumococcal antigen detection by latex agglutination test is as sensitive as the polymerase chain reaction, it seems to be highly specific, and it is rapid and easy to perform. PMID- 7779895 TI - [Evaluation of Mycobacterium fortuitum acyltrehaloses in the serologic diagnosis of pulmonary tuberculosis]. AB - BACKGROUND: Several glycolipids of Mycobacterium tuberculosis are antigenic and their use in the serodiagnosis of pulmonary tuberculosis has been postulated. Acyltrehaloses (SL-IV) are among the strongest antigenic glycolipids of M. tuberculosis; similar compounds have been found in M. fortuitum. The aim of the present study was to evaluate the usefulness of the acyltrehaloses of M. fortuitum in the serodiagnosis of pulmonary tuberculosis. METHODS: Two glycolipids, identified as triacyl- (TAT-MF) and diacyl- (DAT-MF) trehaloses, were studied by an ELISA method. Two independent analyses were carried out. In the first one, IgG and IgM were determined in sera from patients with pulmonary tuberculosis (84-24 bacteriologically not confirmed--), healthy individuals (46) and patients with respiratory pathologies other than pulmonary tuberculosis (38), using TAT-MF. In the second one, IgG was determined in sera from pulmonary tuberculosis patients (34) and from healthy individuals (20), using DAT-MF. RESULTS: The sensitivity of the IgG ELISA using TAT-MF varied, according to the cut-off point, between 79.8 and 39.3%; the specificity values ranged between 83.3 and 98.8%. In sera from bacteriologically not confirmed pulmonary tuberculosis patients the sensitivity was 87.5-45.8%. The sensitivity for IgM was very low using TAM-MF (10.7-2.3%), with specificity values ranging from 77.4 to 100%. The sensitivity and specificity values of IgG using DAT-MF were, respectively, 34.3 9.3% and 90-100%. CONCLUSIONS: The IgG ELISA using TAT-MF has similar values of sensitivity and specificity to those reported for the acyltrehaloses of M. tuberculosis, although this antigen, by itself, can not be used in the serodiagnosis of pulmonary tuberculosis. DAT-MF has no value in the serodiagnosis of pulmonary tuberculosis. PMID- 7779896 TI - [Tuberculosis presenting as diffuse pulmonary infiltrates in AIDS patients: diagnostic performance of clinical samples]. AB - BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, tuberculosis is frequently presented with diffuse pulmonary infiltrates which are indistinguishable from those caused by other respiratory pathogens. It is therefore useful to know the diagnostic performance of different clinical samples. METHODS: We have retrospectively analyzed the clinical histories of 56 patients seen over a 3-year period. All the patients had HIV infection, Mycobacterium tuberculosis isolated in at least one clinical sample and presented with diffuse bilateral infiltrates in thorax radiography. The results of all the clinical samples submitted to the microbiology laboratory. RESULTS: The highest performance in both stainings and cultures were obtained from the biopsy (or aspirate) of adenopathies (93 and 100%, respectively), sputum (57 and 88%) and urine (31 and 64%). A lower than expected sensitivity was obtained in the fibrobronchoscopy samples (bronchoalveolar lavage and transbronchial biopsy). The staining had low sensitivity for predicting positive cultures in all the samples except in the adenopathies. Visualization of granulomas in transbronchial biopsies and bone marrow was more sensitive for diagnosis than the demonstration of resistant acid-alcohol bacilli in the same samples. Globally, rapid diagnosis was obtained in 43 patients (76%). The remaining 13 (24%) patients were not diagnosed until the culture results had been received despite the adequate use of diagnostic procedures. CONCLUSIONS: These findings support the use of empiric treatment when tuberculosis is suspected despite initial negativity of the microbiologic and pathologic examinations following the discarding of other potential causes. PMID- 7779898 TI - [Adnexitis in a woman of fertile age]. PMID- 7779897 TI - [Invasive disease by Haemophilus influenzae type b: current state of prevention by vaccination]. PMID- 7779899 TI - [Depigmented cutaneous lesions in a Equatorial-Guinean woman]. PMID- 7779900 TI - [Foscarnet related vulvar ulcers. Description of 2 AIDS patients]. PMID- 7779901 TI - [Terminal ileum involvement by cytomegalovirus in an immunocompetent patient]. PMID- 7779902 TI - [Infection by Clostridium septicum as a presenting form of colonic neoplasia]. PMID- 7779903 TI - [Cryptococcus neoformans pleuritis in an HIV infected patient]. PMID- 7779904 TI - [Community acquired pneumonia due to Enterococcus. An entity for consideration?]. PMID- 7779905 TI - [Evaluation of a commercial ELISA technique for the diagnosis of respiratory infections by Mycoplasma pneumoniae]. PMID- 7779906 TI - [Demonstration of a cross contamination in the 460TB Bactec system by molecular typing of the strains with IS6110]. PMID- 7779907 TI - [Streptococcus agalactiae infections and toxoplasmosis in pregnancy]. PMID- 7779909 TI - [Edemas as a form of presentation of spotted Mediterranean fever]. PMID- 7779908 TI - [Macroscopic hematuria secondary to the administration of intravenous pentamidine]. PMID- 7779910 TI - FDA reform: arguments on both sides. PMID- 7779911 TI - In vitro and in vivo transfer and expression of human surfactant SP-A- and SP-B associated protein cDNAs mediated by replication-deficient, recombinant adenoviral vectors. AB - Congenital pulmonary alveolar proteinosis (CPAP) is a fatal disease of full-term infants that is unresponsive to current medical therapy. It is now recognized that at least some forms of this disorder are associated with a deficiency of SP B, one of the surfactant-associated proteins, as well as probable aberrations in the surfactant-associated proteins SP-A and SP-C. Given these developments, it is logical to hypothesize that CPAP may be amenable to gene therapy, in which the human SP-B cDNA, and possibly the cDNAs of the other surfactant associated proteins, are transferred to the epithelium of the lower respiratory tract. We constructed replication-deficient, recombinant adenovirus vectors in which a constitutive viral promoter drives the expression of the DNAs for the surfactant associated proteins, SP-B (AdCMV.SP-B) and SP-A (AdCMV.SP-A). Following infection of the human lung A549 epithelial cell line with these vectors in vitro, the appropriately sized mRNAs for these cDNAs were detected, whereas cells infected with a control virus or uninfected cells produced none. Western blots demonstrated expression of these proteins, including appropriate processing of the hydrophobic protein, SP-B. Following in vivo intratracheal infection of rats with these vectors, Northern analysis of the lungs revealed appropriately sized mRNAs for these cDNAs whereas rats infected with control virus or uninfected rats show no hybridization with the human surfactant-associated protein probes. In the AdCM-V.SP-A-infected rats, Western blots confirmed the overproduction of the human SP-A protein in both the bronchoalveolar lavage and lung homogenates compared to controls. Thus, it is feasible to utilize adenovirus vectors to transfer and express the human surfactant associated protein cDNAs in vitro and in vivo, presenting a possible mode of therapy for CPAP, as well as other surfactant deficiency states such as the neonatal respiratory distress syndrome and possibly the adult respiratory distress syndrome. PMID- 7779912 TI - The effect of selection for high-level vector expression on the genetic and functional stability of a single transcript vector derived from a low leukemogenic murine retrovirus. AB - Single-gene murine leukemia virus-based retroviral vectors carrying the G418 resistance gene (neo) under transcriptional control of the long terminal repeat were used to study the effect of selection on long-term vector expression in a murine lymphoid cell line, L691. We used two isogenic vectors carrying either a strong or a weak transcriptional enhancer from low-leukemogenic Akv and high leukemogenic SL3-3 murine leukemia virus, respectively. Effects of G418 selection were studied at the level of vector-transduced cell populations and at the level of single-vector-transduced cell clones obtained without selection for vector expression. Selection for vector expression prior to isolation of cell clones changed the range of vector expression for the two populations of cell clones. Cell clones harboring the Akv enhancer, isolated without selection and then subjected to prolonged growth under selective conditions, exhibited no mutations in the enhancer region or major vector rearrangements although showing increased vector expression in some cases. Our results are discussed in terms of retrovirus mediated gene transfer strategies employing selection for expression of a selective marker in single-gene or bicistronic vectors with a low- or nonleukemogenic virus-derived backbone. PMID- 7779913 TI - Polyoma virus pseudocapsids as efficient carriers of heterologous DNA into mammalian cells. AB - Polyoma virus VP1 pseudocapsids, generated from a recombinant baculovirus, have been successfully used to transfer exogenous DNA stably into rodent (rat-2) cells. To evaluate the efficiency and biological usefulness of this route for introducing heterologous DNA into cells, the gene for a transforming deletion mutant of the middle T antigen of polyoma virus, dl8 MT, was used initially. Whereas the amount of DNA packaged together with pseudocapsids was found to be variable (2-30%), even at low efficiency its transfer as biologically functional information was high. The dl8 MT gene was stably transferred and integrated in low copy numbers into the host chromosome. Transformed cell lines (derived from single foci) were shown to produce high levels of the corresponding mutant protein, which was active in an in vitro protein kinase assay. In comparisons with the calcium phosphate DNA coprecipitation procedure (or lipofectin route), the VP1 pseudocapsid approach was shown to have many advantages in terms of maintenance of DNA fidelity and increased efficiency of gene expression. This system was also assessed for its ability to transfer into and express the chloramphenicol acetyl transferase (CAT) gene in a human liver cell line. Here again, the assay for functional CAT expression showed the pseudocapsid transfer procedure to compare favorably with lipofectin transfer. In another transient assay, a low-level endogenously expressed gene, p43, was complexed with pseudocapsids and transferred into human embryo lung fibroblasts, thereby increasing the expression levels. The ease of production of VP1 pseudocapsids, coupled with their efficient transfer of biologically useful information, should make this route of gene delivery an attractive proposition for further exploration with regard to gene therapy. PMID- 7779914 TI - Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector. AB - In this report, we present data showing that a recombinant adenoviral vector (Ad.RSVIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist protein (IL-1ra) can genetically modify synoviocytes both in vitro and in vivo. Human synoviocytes infected with Ad.RSVIL-1ra in vitro expressed and secreted high levels of human IL-1ra that were detected by ELISA of tissue culture supernatants. New Zealand White rabbits that received intra-articular injections of Ad.RSVIL-1ra expressed transgenic IL-1ra in synoviocytes, and secretion was detected for at least 4 weeks post-infection. Further, biological activity of the transgenic IL-1ra was demonstrated by its ability to inhibit IL-1-induced prostaglandin E2 (PGE2) synthesis in vitro and IL-1-induced glycosaminoglycan (GAG) degradation in vivo. These data demonstrate that recombinant adenoviral vectors can mediate the intra-articular expression of anti-inflammatory proteins and may be a reasonable method to deliver therapeutically relevant proteins for the regional treatment of synovial inflammation. PMID- 7779915 TI - Bacterial lipopolysaccharide copurifies with plasmid DNA: implications for animal models and human gene therapy. AB - During the course of gene therapy experiments in rodents, using intramuscular injections of plasmid DNA derived from Escherichia coli, we noted dose-related toxicity. This observation prompted a search for possible contaminants of DNA samples. We used the highly specific and sensitive limulus amoebocyte lysate assay (LAL), to monitor endotoxin bioactivity in DNA samples, and found plasmid DNA derived from standard E. coli bacterial strains, using traditional DNA isolation protocols, to be heavily contaminated with endotoxin, or lipopolysaccharide (LPA). Standard DNA isolation procedures resulted in the copurification of up to 500 micrograms/ml of LPS. LPS is a potent inducer of cytokines and other inflammatory mediators, and may complicate the use of naked DNA in gene therapy. The copurification of endotoxin with plasmid DNA also has important implications for in vitro transfection studies and microinjection of DNA into embryos. A simple and efficient protocol to reduce LPS contamination of plasmid DNA was developed. The conversion of intact bacteria to spheroplasts prior to the isolation of plasmid DNA, incubation with lysozyme, treatment with the detergent n-octyl-beta-D-thioglucopyranoside (OSPG) and polymyxin-B (PMB) chromatography, allowed the isolation of plasmid DNA containing less than 50 ng/ml LPS. This represents a 10,000-fold reduction in LPS contamination, compared to conventional methods of plasmid DNA purification, avoids potentially toxic reagents such as ethidium bromide, and produces a higher yield of plasmid DNA. PMID- 7779917 TI - Guidance on making proposals to conduct gene therapy research on human subjects. Report of the United Kingdom Health Ministers' Gene Therapy Advisory Committee. PMID- 7779916 TI - Construction of a novel bovine papillomavirus vector without detectable transforming activity suitable for gene transfer. AB - Bovine papillomavirus type 1 (BPV-1)-derived vectors may be useful for gene therapy because of their episomal maintenance at intermediate to high copy number and stable, high-level expression of gene products. To increase the safety of BPV 1 for human trials, the transforming early genes E5, E6, and E7 were deleted and a new vector, B45-Neo, was established and its transforming potential, episomal maintenance, and cDNA expression determined. Deletion of E5, E6, and E7, caused a decrease of the copy number to 80 in 3T3 fibroblasts when B45-Neo was compared to the parent vector that supported more than 1,000 copies per cell. No significant difference in the copy number, which ranged between 13 and 30 per cell, was detected in other cell lines of murine or human origin. The episomal maintenance of B45 and its ability to express cDNA was retained. B45-Neo, in contrast to BMG Neo, however, was unable to transform NIH-3T3 and C1271 cells in soft agar colony assays. Unlike BMG-Neo, B45-Neo did not cause morphological changes in 3T3 and C1271 cells characteristic for transformation. It is concluded that B45-Neo is an efficient expression vector without detectable transforming activity and may be useful and safe for human gene therapy trials. PMID- 7779918 TI - Phase I study of non-replicating autologous tumor cell injections using cells prepared with or without GM-CSF gene transduction in patients with metastatic renal cell carcinoma. PMID- 7779919 TI - Phase I study of transfected cancer cells expressing the interleukin-2 gene product in limited stage small cell lung cancer. PMID- 7779920 TI - Markers of past syphilis in HIV infection comparing Captia Syphilis G anti treponemal IgG enzyme immunoassay with other treponemal antigen tests. AB - The sensitivity of the Captia Syphilis G anti-treponemal IgG enzyme immunoassay (EIA-IgG) was compared with the Treponema pallidum haemagglutination assay (TPHA) and the Fluorescent Treponemal Antibody Absorbed (FTA-Abs) test as a marker for past syphilis in 28 HIV-infected and 31 HIV-negative patients with a past history of syphilis. The specificity of EIA-IgG was compared in 89 patients without a history of syphilis who were known to be HIV antibody positive with a control group of 89 patients who had tested HIV negative. In patients with a past history of syphilis each treponemal test (EIA-IgG, TPHA and FTA-Abs) gave a lower sensitivity (82%, 86%, 79%) in the HIV-positive group than in the HIV-negative group (97%) but the difference was significant only in the case of the FTA-Abs test (P < 0.05). In the HIV-positive patients 11% (3/28) were negative in all 3 treponemal tests while 25% (7/28) were negative in at least one treponemal test. In patients without a past history of syphilis the EIA-IgG antibody index in the HIV-positive group (0.436) was significantly higher than in the HIV-negative group (0.378): the specificity, however, was similar in the HIV-positive (100%) and HIV-negative group (99%). We conclude that the Captia Syphilis G anti treponemal IgG enzyme immunoassay is of similar specificity in HIV-positive and HIV-negative patients and is of similar sensitivity to the TPHA and FTA-Abs as a marker of past syphilis in HIV-infected patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779921 TI - Impact of counselling on safer sex and STD occurrence among STD patients in Malawi. AB - In developing countries where professional manpower and basic supplies are lacking for STD control, low-cost prevention strategies must be explored. This study assesses the impact of counselling on STD treatment and prevention in Malawi. Increases in safer sex practices are used as indicators of prevention behaviour. A pre-test post-test control group design over a 4-month interval was conducted in 1991 in 2 comparable hospitals approximately 100 km apart. STD was diagnosed symptomatically and Knowledge Attitude Practice and Behaviour (KAPB) data collected using a structured questionnaire. In one group, trained counsellors discussed modes of transmission and prevention of STD/AIDS including a condom demonstration; symptoms and treatment of STDs; partner notification; risk taking and reasons for doing so; and motivations for behaviour change. The results show that counselling reduces the occurrence of STDs; increases concern for sexual partners; increases knowledge about and use of condoms; reduces mean number of partners; and reduces health costs due to fewer hospital visits. Although the observed behaviour change was short term, these outcomes argue in favour of counselling as a low-cost effective strategy for STD control. PMID- 7779922 TI - Temporal changes in the sensitivity of Neisseria gonorrhoeae to penicillin in Edinburgh, Scotland. AB - Increased resistance of Neisseria gonorrhoeae to penicillin has been reported from many centres around the world since the introduction of antibiotic therapy in the 1940s. This study reports the temporal changes in gonococcal penicillin sensitivity over a 3-year period. All patients with a diagnosis of gonorrhoea in the city of Edinburgh, Scotland between 1990 and 1992 were included in the study. Penicillin sensitivity of isolates was analysed in relation to the sex and sexual orientation of the patient and the antibiotic therapy given. Four hundred and twenty-seven new patient episodes of infection occurred of which penicillin sensitivities were available in 426. Eleven episodes of PPNG infection occurred. Chromosomally mediated penicillin resistance did not increase over the study period. No differences were evident in the sensitivity of isolates from homosexual and heterosexual patients. Unlike many other areas the relative resistance of N. gonorrhoeae is not increasing in Edinburgh at present. This may relate to local antibiotic policies combined with intrinsic characteristics of N. gonorrhoeae itself. Unlike previous reports there did not appear to be any increased resistance to penicillin in isolates from gay men. PMID- 7779923 TI - Response to podophyllotoxin treatment of genital warts in relation to HIV-1 infection among patients in Dar es Salaam, Tanzania. AB - Forty-two Tanzanian patients with genital warts were treated with 0.5% podophyllotoxin solution (Wartec) for 3 days. Thirteen patients (30.9%) were cured and a further 7 patients (16.7%) had more than 50% of lesions cleared at 6 weeks, while 19 patients were resistant to treatment. Three patients had a recurrence of lesions after an initial response. Thirty-three patients were tested for serological evidence of infection with human immunodeficiency virus (HIV) and 15 (45.5%) patients were shown to be HIV-1 antibody positive. The response to treatment was analysed in relation to HIV antibody status. The cure rate was significantly higher in HIV seronegative patients (8/18 = 44.4%) compared to HIV seropositive patients (1/15 = 6.7%) (P = 0.018). We conclude that podophyllotoxin treatment provides a useful non-hospital based treatment for genital warts, but HIV infection appears to contribute to the failure of treatment for genital warts. PMID- 7779925 TI - HIV infection in a long-term renal transplant recipient. PMID- 7779926 TI - Successful prevention of recurrent pneumonia caused by Pseudomonas aeruginosa in a patient with AIDS. PMID- 7779924 TI - HIV-1 variants in South and South-East Asia. AB - HIV spread in South and South-East Asia is most alarming, and genetic variability of HIV-1 is an important consideration in vaccine development. In this study, we examined the third variable (V3) region of env gene of HIV-1 variants prevalent in Thailand, Malaysia, India, and the Philippines. By phylogenetic tree analyses, an HIV-1 variant from an injecting drug user (IDU) in Thailand belonged to subtype B, and HIV-1 variants from 2 IDUs in Malaysia were classified into 2 subtypes, B and E. One HIV-1 variant from a male homosexual in the Philippines belonged to subtype B. Out of 8 HIV-1 variants from sexually transmitted disease patients in India, 7 belonged to subtype C, and one to subtype A. Although the total number of individuals examined in this study was limited, 4 HIV-1 subtypes were found in South and South-East Asia and large international movements of HIV 1-infected individuals in this region could induce global dissemination of these HIV-1 variants. PMID- 7779927 TI - Disseminated cutaneous leishmaniasis in an HIV-infected patient. PMID- 7779928 TI - Multiple tropical pathology in an HIV-positive man. PMID- 7779929 TI - Investigation and management guide for sexually transmitted diseases (excluding HIV). PMID- 7779930 TI - High prevalence of herpes simplex virus type 1 in female anogenital herpes simplex. PMID- 7779931 TI - Mycoplasma genitalium in non-gonococcal urethritis. PMID- 7779933 TI - Is there a risk of human immunodeficiency virus (HIV) transmission in dialysis centres? PMID- 7779932 TI - Unilateral vulval hypertrophy and Crohn's disease. PMID- 7779935 TI - Balanitis xerotica obliterans. PMID- 7779934 TI - Epidemiological characteristics of human immunodeficiency virus type-2 infection in Africa. AB - There are things yet to be clarified about African HIV-2 infection, compared to HIV-1 infection. However, the epidemiological characteristics have gradually been elucidated through various studies. HIV-2 infection is believed to have existed in the 1960s in Africa and is presently epidemic in West Africa. The HIV-2 seropositive rate for the general population is higher in urban regions than in rural areas. The peak age of persons infected with the HIV-2 tends to be higher than that of persons infected with the HIV-1, but no sex difference was recognized between the HIV-2 and HIV-1 seropositive rates. Sexual contact, mother to-child transmission and blood transfusion have been confirmed as HIV-2 transmission modes. Prostitutes and patients with other STD are recognized as being high-risk groups for the HIV-2 infection. Patients who are infected with both HIV-1 and HIV-2 have also been identified, but it is suggested that the pathogenicity of HIV-2 is lower than that of HIV-1. PMID- 7779936 TI - HIV at the hospital/general practice interface: bridging the communication divide. AB - Good communication between hospital HIV units and general practitioners is essential if people with HIV are to receive appropriate medical care in the community. However, in the UK the experience of general practitioners looking after people with HIV has been that communication is often inadequate. The reasons for this relate to the way that the HIV epidemic has evolved in the UK and the way that health services providing care in HIV have developed. In this review we will examine the causes of the present situation and suggest ways of improving communication which will have beneficial effects on the care of people with HIV. PMID- 7779937 TI - Preventing unprotected anal intercourse in gay men: a comparison of two intervention techniques. AB - This study compared the effectiveness of getting gay men to evaluate the self justifications they use when breaking their safe sex rules to that of a standard approach to AIDS education. Men (n = 109) who had 'slipped up' (broken their safe sex rules by having unprotected anal intercourse) kept diaries of their sexual behaviour for 16 weeks. After 4 weeks they were allocated to one of 3 conditions, 2 involving brief interventions--Self-justifications (evaluation of self justifications) and Standard (examination of posters used in AIDS education)--and a Control (diary only). At the time of the intervention, more members of the Self justifications than the Standard group thought that it would help them not to slip up. In the post-intervention period, the 3 groups did not differ in the incidence of sexual activity or in the proportion who slipped up at least once, but the Self-justifications group were less likely to have had multiple slip-ups. Three possible explanations are offered for the effectiveness of the Self justifications intervention. This approach may provide a useful alternative to standard techniques of AIDS education. PMID- 7779939 TI - [Epidemiologic research and clinical research: a proposal for their integration]. PMID- 7779938 TI - Prior sexual assault reported by male attenders at a department of genitourinary medicine. AB - One-hundred-and-fifty male patients who attended the department of genitourinary medicine (GUM) completed a questionnaire which enquired into a past history of sexual assault and asked certain details about the assault and various sequelae of such an experience. Twenty-one men gave a history of sexual assault, 11 of whom had been abused before the age of 16, 7 afterwards and 3 in both age groups. Victims of such an assault were more likely to be homosexual or bisexual than heterosexual. The substantial majority i.e. 104 (81%) of the 129 patients who had not been assaulted in the past had been brought up by both natural parents. However, of the 21 males who reported a history of previous sexual abuse only 11 (52%) had been raised by both natural parents alone and 9 of the remaining 10 who divulged such information had been brought up in other circumstances. The association between not being raised entirely by both natural parents and a history of previous sexual assault was significant (P < 0.01). Overall, physical contact of a sexual nature was the most commonly reported type of abuse, followed by anal and then by oral penetration. All of the perpetrators of assault were male except in one instance. Only 3 cases of assault were reported to the police or other agencies. Those who had been abused as minors were more likely to acknowledge subsequent psychological difficulties and to have obtained professional counselling. This problem is a significant one which goes largely undetected in GUM departments and elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779940 TI - Platelet function in patients with lupus anticoagulant and thrombosis. AB - In a group of 337 patients with a history of thrombotic episodes, pregnancy losses and/or thrombocytopenia, 66 cases of lupus anticoagulant (LA) were found. Spontaneous platelet aggregation and the aggregatory responses of platelet rich plasmas (PRP) from 14 patients, with a history of thrombotic episodes, with anticardiolipin (ACA) levels above 21 IgG antiphospholipid antibodies units and normal platelet counts were studied and compared with those of 8 patients with history of thrombosis and negative LA and ACA (controls). Epinephrine, adenosine diphosphate, collagen and ristocetin were used as platelet aggregation inducers. Early collagen-whole blood interaction (BASIC WAVE), as a measure of platelet recruitment, and the levels of von Willebrand factor were also determined. The results of each test were compared with those of nine patients, used as controls, with thrombotic antecedents but negative LA and ACA. None of the patients with LA, or the control group, showed spontaneous platelet aggregation. The aggregatory responses, when epinephrine, ADP or collagen were added to the patient's PRP, were within normal range in most cases (64.2%, 52% and 72% respectively). The highest rate of hyperaggregation after the above mentioned inducers, was 12% and corresponded to the response to collagen. On the contrary, platelet aggregation rate with ristocetin was higher than 100% in 61.0% of the problem group, with no significative difference from the controls. The BASIC WAVE was of low rate and similar in the two groups studied. The von Willebrand factor was significantly higher (150 +/- 55%) in the problem group than in the controls (98 +/- 25.6%) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779941 TI - [Creutzfeldt-Jakob disease. Report of 2 cases]. AB - The authors report two cases of Creutzfeldt Jakob disease in a 48 year old woman and a 60 year old man. This demential disorder is induced by a non conventional virus and its characterized from a clinical point of view by progressive dementia, myoclonus and seizures, it follows a subacute course with progressive deteriorization that invariably leads to death. Neuropathological features include: neuronal loss, astrocytosis and neuropil vacuolization in cortical areas of the brain. A review of the medical literature suggests that these constitute the fourth and fifth case respectively reported in Venezuela, of this unusual neurological disorder. This paper emphasizes the clinical and neuropathological features of this entity and suggests its inclussion among the differential diagnoses of the different demential processes. PMID- 7779942 TI - [REMENEN. Mental representation of natural whole numbers]. AB - Study was carried out to find the existence, form of presentation and commonalities and individual differences in the mental representation of natural whole numbers (REMENEN). The design used was an ex-post-factor exploratory and descriptive field study. A questionnaire was developed and administered to a sample of 153 senior students at the Universidad Catolica Andres Bello (UCAB). The hypotheses were: a) that REMENEN exists in all individuals, b) that REMENEN are individual, c) that there are intergroup differences and intragroup similarities in REMENEN according to major field of study and sex. The existence of REMENEN in the great majority of individuals was demonstrated as well as their individuality in all subjects. There were no significant differences according to major or sex, and no significant intragroup similarities. The present study opens the field for a new line of research and allows a relationship between isolated statements regarding numbers made by Galton, Jung and some cognitive psychologists. PMID- 7779943 TI - [Sudanophilic cavitating leukodystrophy: adult familial form]. AB - Sudanophilic cavitating leukodystrophy is an unusual disorder of the cerebral white matter, clinically characterized by deafness, mental retardation, behavioural alterations and lesions of the descending long tracts. Neuropathological features include: extensive subcortical and deep central demyelination, conspicuous astrocytosis and macro and micro cavitation. We describe a 34 year-old male with personal and family history, clinical features and neuropathological changes consistent with Sudanophilic cavitating leukodystrophy. As far as our knowledge is concerned this constitutes the first report of this entity in Venezuela. PMID- 7779944 TI - Fibrosing granulomas in the equine liver and peritoneum: a retrospective morphologic study. AB - Fibrosing granulomas were found in the liver and occasionally on the intestinal and diaphragmatic serosae and in the lung of 11 horses submitted for necropsy. Although these granulomas were considered incidental findings in most of the horses, they had caused liver failure in 1 horse. The granulomas typically were characterized by a dense collagenous core that frequently was mineralized. The periphery contained a rim of inflammatory cells. Only in 1 of the 11 horses was there evidence of an egg shell suggestive of schistosomes. Schistosomal eggs were not detected in the feces of the horses. The typical architecture of the granulomas combined with the occasional finding of a residual egg led to the circumstantial conclusion that the fibrosing granulomas were the result of chronic schistosomiasis of undeterminable origin. PMID- 7779946 TI - Spontaneous glomerulonephritis in swine. AB - In this investigation, 32 cases of naturally occurring glomerulonephritis in swine were studied retrospectively (1973-1993). Almost all affected pigs were crossbred and more than half were growing pigs. Nearly two thirds of the pigs showed gross renal lesions characterized by bilateral kidney enlargement, palor, edema, and/or cortical petechiation. The most commonly encountered extrarenal lesions were serous bodily effusions and gastric ulcers. The renal disease was considered the primary cause of death in 11 pigs. Histologically, the renal lesions in all pigs were characterized by a generalized and global proliferative glomerulonephritis. Mesangioproliferative glomerulonephritis was diagnosed in 2 pigs, whereas the glomerular lesions found in the other pigs (30/32) were characterized by a proliferative and exudative glomerulonephritis frequently associated with crescent formation. In all pigs, there was histologic evidence of proteinuria. A focal necrotizing vasculitis was found in the kidneys of 7 pigs. Although probably of immune origin, the precise etiopathogenesis of the porcine glomerulonephritis described herein after remains unknown. PMID- 7779945 TI - Chronic generalized obliterative arteriopathy in cattle: a sequel to sheep associated malignant catarrhal fever. AB - Malignant catarrhal fever (MCF) in cattle is generally associated with a short clinical course and a high case fatality rate (90-95%). The lesions in cattle that survive acute MCF for a prolonged period or appear to recover have not been documented. In a naturally occurring outbreak of MCF in a herd of beef cattle in Wyoming, 7 of 84 yearling heifers (8.3% of replacement herd) and 2 of 230 cows (0.9% of cow herd) developed clinical signs of pyrexia, mucopurulent discharge, bilateral keratitis, and weight loss following contact with ewes that had lambed 34-62 days earlier. Six of 9 affected cattle were examined postmortem following clinical signs (CS) that developed 2-150 days earlier. Three cattle with CS for < or = 39 days had lesions of regional lymphadenopathy and widespread severe segmental lymphoid arteritis-phlebitis that were typical of acute MCF, and proliferative intimal lesions were present in a small proportion of arteries at days 20 and 39 of CS. By contrast, 3 cattle that survived to 90, 105, and 150 days after clinical onset had distinctive arterial lesions in multiple organs, characterized by proliferative concentric fibrointimal plaques, disrupted inner elastic lamina, focally atrophic tunica media, and vasculitis of variable severity. Immunohistochemical and ultrastructural examination of intimal plaques identified the predominant cellular component to be smooth muscle cells with a contractile phenotype. No viral structures were seen. Serologic studies, using a competitive inhibition enzyme-linked immunosorbent assay (CI-ELISA) that detects antibody to an epitope broadly conserved among isolates of the MCF virus, found that 2 chronically affected cattle were serologically positive between days 42 and 100 of CS, with seroconversion in 1 animal between days 52 and 73 of CS. Seroprevalence was 7.9% in the 76 remaining healthy animals of the replacement heifer herd and 40% (75% in adult sheep and 4% in lambs) in the in-contact sheep flock 77 days after onset of CS in the index case. This episode suggests that, in addition to the common and well recognized acute form of MCF in cattle, this viral infection encompasses a disease spectrum that includes chronic disease and partial to "complete" clinical recovery, and in recovered animals chronic obliterative arteriopathy is the preeminent lesion. PMID- 7779947 TI - Comparison of argyrophilic nucleolar organizer regions (AgNORs) and mitotic index in distinguishing benign from malignant canine smooth muscle tumors and in separating inflammatory hyperplasia from neoplastic lesions of the urinary bladder mucosa. AB - Staining for argyrophilic nucleolar organizer regions (AgNORs) has proven useful in differentiating recurrent or malignant neoplasms from less aggressive or benign ones. We applied this stain to benign and malignant smooth muscle tumors and to hyperplastic and carcinomatous lesions in the urinary bladder of dogs in an effort to determine its utility in diagnostic situations. The stain was simply performed, and the results were repeatable for different staining intervals and between staining batches. For smooth muscle tumors, enumeration of AgNORs in 100 nuclei was about as efficient as mitotic index in correctly categorizing histologically benign and malignant neoplasms. The mean number of AgNORs/100 nuclei for leiomyomas was significantly less than that obtained for leiomyosarcomas and significantly greater than that obtained for normal smooth muscle. Counts for smooth muscle tumors correlated with the mitotic indexes. Counts by an individual observer were repeated without introducing significant variation, but there was variability between observers, particularly in AgNOR counts for leiomyosarcomas. AgNORs were not useful in separating hyperplastic or polypoid cystitis from transitional cell carcinoma, misclassifying both. Mean AgNOR counts for these 2 conditions did not differ at the 5% level of significance; mitotic index was more efficient at separating the 2 conditions. There was no correlation between mitotic index and AgNOR in urinary tract mucosal specimens. This easily prepared stain may be useful in separating benign and malignant smooth muscle tumors, although AgNORs were less contributory to diagnosing mucosal lesions of the urinary bladder of dogs. PMID- 7779948 TI - Isolation and culture of large vessel endothelium from white-tailed deer (Odocoileus virginianus). AB - Endothelial cells were obtained from white-tailed deer carotid arteries and umbilical vessels by instilling a weak collagenase type II solution. Cell growth was best when cultures were grown in plates coated with either fibronectin or laminin. Several commercially available media supported the growth of these cells when supplemented with a commercially available endothelial growth supplement and 10% fetal calf serum. Cells obtained could be characterized as endothelium by ultrastructural characteristics and by the uptake of fluorescent acetylated low density lipoprotein. Cells stained positive for factor VIII-related antigen up to passage 2, but staining was inconsistent by passage 3, and no immunoreactivity could be demonstrated after passage 4. PMID- 7779949 TI - Bovine viral diarrhea serologic diagnostic reagents prepared from bacterially expressed recombinant proteins. PMID- 7779950 TI - Neutralizing activity in bovine secretions against foot-and-mouth disease virus. PMID- 7779951 TI - Group B rotavirus associated with an outbreak of neonatal lamb diarrhea. PMID- 7779952 TI - Inclusion body hepatitis and hemorrhagic enteritis in two African grey parrots (Psittacus erithacus) associated with adenovirus. PMID- 7779953 TI - Recovery of two mycoplasma species from abscesses in a cat following bite wounds from a dog. PMID- 7779954 TI - Rhodococcal abortion and pneumonia in an equine fetus. PMID- 7779955 TI - Antimicrobial susceptibility profiles of multidrug-resistant Salmonella anatum isolated from horses. PMID- 7779956 TI - Evaluation of a commercial system for the identification of gram-negative, nonfermenting bacteria of veterinary importance. PMID- 7779957 TI - Sporadic multicentric lymphosarcoma in a three-year-old bull. PMID- 7779958 TI - Presumptive botulism in cattle associated with plastic-packaged hay. PMID- 7779959 TI - A comparison of three avidin-biotin complex immunoenzyme systems for detection of African swine fever virus antigen in paraffin-embedded tissues. AB - The sensitivity and specificity of 3 avidin-biotin complex (ABC) immunostaining systems were compared on paraffin-embedded tissues from African swine fever virus (ASFV)-infected pigs. Results were also compared with immunofluorescent detection on cryosections of the same tissue for optimal detection of ASFV antigen. The ABC alkaline phosphatase (ABC-AP) and ABC-peroxidase (ABC-PO) systems were at least as sensitive as direct fluorescent antibody (FA) and 10-fold more sensitive than the ABC-glucose oxidase system. Three ABC-AP and 2 ABC-PO chromagens with different counterstains were compared. In addition, 2 fixatives, 2 biotinylation procedures, 7 endogenous peroxidase blocking regimes, 6 tissue adhesives, and 3 mounting media were compared. The ABC-AP system with a red chromagen and hematoxylin counterstaining was preferred and most closely approximated routinely stained pathologic sections. Fixation in paraformalde-hydelysine-periodate fixative preserved ASFV antigen for research studies for at least 3 years. Formalin-fixed tissues retained some staining for up to 10 years. PMID- 7779960 TI - Early infection of interdigitating dendritic cells in the pig lymph node with African swine fever viruses of high and low virulence: immunohistochemical and ultrastructural studies. AB - The role of interdigitating dendritic cells (IDCs) in the early pathogenesis of African swine fever (ASF) was investigated using mandibular lymphoid tissue from normal pigs and pigs inoculated oronasally with highly virulent Lisbon 60 (L-60) and moderately virulent Dominican Republic 1979 (DR-2) ASF virus (ASFV) isolates. Paraffin-embedded tissue sections were immunostained for ASFV antigen and S-100 protein, a marker of IDCs, using an avidin-biotin alkaline phosphatase procedure. Swine IDCs were identified morphologically by light microscopy, electron microscopy, and S-100 immunostaining. Infection with ASFV caused a marked reduction in S-100 staining by 3 days postinfection (DPI) that persisted through 14 DPI. Early ASFV infection of IDCs was demonstrated at 3 DPI by double immunohistochemical staining of cryosections and by transmission electron microscopy. These results support the hypothesis that the failure of a humoral immune response to virulent ASFV may be due to a primary infection of IDCs and the inability of IDCs to initiate an immune response. Infection of IDCs has also been demonstrated with human immunodeficiency virus (HIV-1), and these infections have some aspects in common. PMID- 7779961 TI - Diagnosis of porcine reproductive and respiratory syndrome. AB - The most suitable tissue samples and test procedures for the etiologic diagnosis of porcine reproductive and respiratory syndrome (PRRS) were found to depend on several variables including the age of the pig from which tissues were collected, the stage of infection (acute or persistent), the available complement of diagnostic reagents, and the urgency in obtaining results. When the diagnosis involved acute infection of congenitally or neonatally infected pigs, and susceptible cell culture(s) was available for virus isolation, then both serum and alveolar macrophages (AM) were reliable samples. Alveolar macrophages flushed from infected lungs provided a temporal advantage, however, in that in addition to their use for virus isolation, i.e., from a lysate of AM, they could be cultured in vitro and examined for the presence of viral antigens by immunofluorescence microscopy (FA) as early as 1 hour after they were added to the culture vessel. The examination of AM in this manner also circumvented the need for additional cell cultures to test for infectious virus. Testing presuckling sera by indirect FA for antibodies to PRRS virus also was of diagnostic value and, like FA with AM, could be completed soon after sample collection. For older pigs, AM were more reliable than serum, lungs, or any of 27 other tissues evaluated as diagnostic samples and were often the only samples in which infectious virus and viral antigens were detected when pigs were euthanized more than 3 weeks postexposure. A simple procedure for on-farm collection of AM as well as methods for testing AM for viral antigens and neonatal (presuckling) sera for homologous antibody in a modestly equipped laboratory, such as one that might be maintained by a veterinary practitioner, are described and discussed. PMID- 7779962 TI - African swine fever interference with foot-and-mouth disease infection and seroconversion in pigs. AB - Initial oral infection of pigs with either highly virulent (L-60) or moderately virulent (DR-2) African swine fever virus (ASFV), followed in 3 days with exposure to foot-and-mouth disease virus (FMDV) (tongue inoculation and contact), failed to cause FMDV infection or seroconversion in 18 of 22 L-60-infected pigs and 13 of 34 DR-2-infected pigs. Of the 13 DR-2-infected pigs remaining free of foot-and-mouth disease (FMD), 2 pigs survived to 24 days without antibody to FMDV, despite constant contact with clinically infected pigs with FMD. Three other DR-2-infected pigs never developed FMD lesions but did develop low levels of antibody to FMDV by day 17. A group of larger pig (in which DR-2 is less virulent) infected with DR-2 and then FMDV had a rapid but suppressed immune response to FMDV. Contact pigs introduced 3 days postinoculation and inoculated with FMDV only all became infected with ASFV by contact and died. This remarkably long lasting 1-way interference with FMD infection during acute and subacute African swine fever was not anticipated. Infection with ASFV may have blocked the initial target cells (possibly dendritic cells) necessary for establishment of FMDV infection. PMID- 7779963 TI - African swine fever virus infection of skin-derived dendritic cells in vitro causes interference with subsequent foot-and-mouth disease virus infection. AB - Highly purified skin-derived dendritic cells (SDDCs) isolated from swine skin by a simple novel method were cultured for 24 hours before independent or sequential inoculation with African swine fever virus (ASFV) and foot-and-mouth disease virus (FMDV). By avidin-biotin immunohistochemical staining, ASFV antigen was detected in 50% of SDDCs as early as 1.5 hours postinfection (HPI) and in 80% by 3 HPI when cytopathic effect was noted. Cell lysis was detected with FMDV infection as early as 8 HPI; immunostaining for FMDV antigen was found in 10% of the cells. African swine fever virus replication was detected by transmission electron microscopy in a high percentage of SDDCs by 11 HPI. Sequential infection with FMDV 3 hours after ASFV inoculation blocked FMDV infection. These findings demonstrate that both ASFV and FMDV infect dendritic cells of Langerhans cell type in vitro and ASFV interferes with FMDV infection. PMID- 7779964 TI - Detection and subtyping of foot-and-mouth disease virus in infected cattle by polymerase chain reaction and amplified VP1 sequencing. AB - Fast and accurate detection of foot-and-mouth disease (FMD) outbreaks is needed to limit spread of the disease by proper vaccination. The use of the polymerase chain reaction (PCR) has revolutionized the way in which viral diseases are diagnosed. Sequence analysis of the amplified VP1 sequence can enable the classification of FMD virus detected in the morbid animal. PCR assays were carried out to identify the virus and its serotype in suspect animals from 2 outbreaks of FMD type O virus. Sequence analysis of the amplified VP1 cDNA showed 78% homology with O1K and over 95% homology between the samples. These findings suggest that the 2 outbreaks were due to infection with the same virus serosubtype. PMID- 7779965 TI - Survival of pseudorabies virus on swabs maintained under standard field sample shipping conditions. AB - Pseudorabies virus survival was compared using three different types of applicator swabs in Eagle's minimum essential medium held under shipping conditions (packed with frozen gel packs) for up to 96 hours. Virus titer decay rates for dacron-tipped applicators were not statistically different from those of controls. Titer decay rates were statistically different from controls for cotton- and calcium alginate-tipped applicators. With the lowest input virus titer, virus was detectable up to 96, 72, or 24 hours after inoculation for dacron-, cotton-, and calcium alginate-tipped applicators, respectively. Dacron tipped applicators were chosen to evaluate pseudorabies virus survival on tonsil swabs collected from experimentally challenged or contact control pigs to simulate field sampling and shipping conditions. Virus was still detectable in 20 of 24 swab samples after 72 hours in cell culture medium under shipping conditions. PMID- 7779966 TI - Evaluation of a blocking ELISA using monoclonal antibodies for the detection of porcine epidemic diarrhea virus and its antibodies. AB - Two blocking enzyme-linked immunosorbent assays (ELISAs) involving the use of monoclonal antibodies (MAb) as capture and detecting agents and an indirect fluorescence test (IFT) were used for the detection of porcine epidemic diarrhea virus (PEDV) antigen or its antibodies. In the ELISA for viral antigen detection, the blocking step is accomplished by incubation of fecal samples, in duplicate wells, with PEDV-specific positive or negative serum, whereas in the ELISA for antibody detection the blocking step is accomplished by incubation of serum samples with a gut-origin virus suspension. All the methods developed were used to monitor an experimental infection in piglets with the CV-777 strain of PEDV and a natural PED outbreak in a swine fattening unit. The antigen-detection ELISA was able to detect PEDV shedding for a longer time than have previously described methods. The blocking ELISA for antibody detection was able to detect the serum antibody response sooner after PEDV infection than did IFT. PMID- 7779967 TI - Evaluation of an antigen-capture ELISA for detection of bovine viral diarrhea virus in cattle blood samples. AB - From blood samples routinely received for bovine viral diarrhea (BVD) diagnosis, 860 samples without antibodies to BVD virus were examined in both virus isolation and in an antigen-detecting enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies (MAbs) against the nonstructural BVD virus protein p125/p80. A total of 843 samples (98%) were positive (n = 170, 20%) or negative (n = 673, 78%) in both tests, corresponding to an agreement of kappa = 0.94. Among 17 samples with diverging results, 3 were from animals transiently infected with BVD virus, and 5 came from clinically affected animals. The reactivity of the MAbs was controlled against 387 field isolates of BVD virus. All were detected by the MAbs, thereby confirming the general view that the p125 virus protein is highly conserved among different BVD viruses. PMID- 7779968 TI - Immunoperoxidase detection of ophidian paramyxovirus in snake lung using a polyclonal antibody. AB - In a retrospective study of proliferative interstitial pneumonia in viperid and nonviperid snakes, formalin-fixed, paraffin-embedded lungs from 52 snakes were screened for immunohistochemical reactivity to ophidian paramyxovirus. All snakes were from zoological collections that experienced mortalities attributed to paramyxovirus infection. Of the 52 snakes, 47 had pulmonary lesions compatible with ophidian paramyxovirus infection. Histologic changes in affected lungs included hyperplasia and hypertrophy of septal and faveolar epithelial cells, loss of ciliated cells, mixed leukocytic interstitial infiltrates, fibrinonecrotic exudate in the lumen of proximal and distal faveolar compartments, and occasional epithelial syncytial cell formation or intraepithelial eosinophilic intracytoplasmic inclusions. Lungs were immunohistochemically stained for paramyxovirus antigens by utilizing rabbit polyclonal antibodies against a paramyxovirus isolate from a black mamba (Dendroaspis polyepis polyepis). Virus infection in 6 snakes was confirmed by virus isolation from frozen lung tissue. Of the 6 lungs from which paramyxovirus was isolated, 5 lungs stained positively for viral antigens utilizing antisera to the black mamba isolate. Altogether, 36 lungs stained positively for paramyxovirus antigens. There was multifocal to diffuse linear staining of the lumenal surface of faveolar epithelium, and there were multiple foci of granular cytoplasmic staining. Immunohistochemical staining of formalin-fixed lungs from snakes with proliferative interstitial pneumonia was helpful as a routine diagnostic test for substantiating a diagnosis of ophidian paramyxovirus infection. PMID- 7779969 TI - Outbreaks of yersiniosis caused by Yersinia pseudotuberculosis in farmed cervids. AB - Yersiniosis, caused by Yersinia pseudotuberculosis, was diagnosed in 25 deer submitted to the Veterinary Diagnostic Laboratories of the Ontario Ministry of Agriculture and Food from 8 farms in Ontario, Canada, over the 4-year period of January 1990 to December 1993. The organism was cultured, usually in large numbers, from the intestines and, less frequently, mesenteric lymph nodes and/or the spleen of 13 red deer (Cervus elaphus), 6 elk (C. e. canadiensis), 4 fallow deer (Dama dama), and 2 red deer-elk hybrids. Outbreaks occurred almost exclusively in the fall (September-November) and affected recently weaned calves, 4-6 months old. Sudden death usually signalled the start of an outbreak. Outbreaks often occurred during inclement weather; usually a sudden cold snap, with or without rain, after a period of relatively mild fall weather. At necropsy, the animals were usually emaciated and dehydrated, and the perineum and tail were sometimes fecally stained. The small and large intestines were congested and filled with serofibrinous and/or seroanguineous fluid. Mesenteric lymph nodes were edematous and congested. Microabscesses surrounding large bacterial colonies in the lamina propria in the jejunum and ileum were typical lesions seen histologically. Peyer's patches were depleted and sometimes contained microabscesses. Purulent lymphadenitis associated with bacterial colonies was the prominent histologic lesion in mesenteric lymph nodes. PMID- 7779970 TI - Detection of anti-listeriolysin O in dairy cattle experimentally infected with Listeria monocytogenes. AB - A dot-blot assay and an enzyme-linked immunosorbent assay (ELISA) to detect listeriosis in dairy cattle were developed that detected anti-listeriolysin O antibodies in the serum of cows experimentally infected with Listeria monocytogenes. The tests utilized purified listeriolysin O (LLO) as the detection antigen and streptolysin O (SLO) to absorb cross-reacting antibodies. The two tests were compared with an agglutination test that used formalin-killed whole L. monocytogenes cells. Blood samples were collected periodically from 17 cows after intramammary gland infection, and the development of anti-LLO antibodies was followed by an agglutination test, the dot-blot test, and the ELISA. In general, an agglutination titer of > 640 was needed for a positive dot-blot anti-LLO test for nonpregnant cows. However, 1 pregnant cow with an agglutination titer of 20 was positive in the dot-blot test. The ELISA was as sensitive as the dot-blot assay but gave a quantitative measurement to distinguish serum samples of positive reactors from cross-reactors. The specificity of the LLO-based tests was further evaluated using serum from cows that had been experimentally infected with Staphylococcus aureus, 17 of which had agglutination titers for L. monocytogenes > 640. These elevated agglutination titers were probably due to cross-reacting bacterial antigens because serum from 9 of 17 of these animals did not react to the purified LLO antigen. A positive response to the LLO-based dot blot and ELISA assays is indicative of previous or current infection with L. monocytogenes. PMID- 7779971 TI - Prevalence and serovars of leptospira involved in equine abortions in central Kentucky during the 1991-1993 foaling seasons. AB - In this study, the prevalence of leptospira-induced abortions/stillbirths for the past 3 foaling seasons (1991-1993) was determined, and fetal tissues and/or the mare's urine from positive cases were cultured in an attempt to isolate and identify the leptospira serovars responsible for the abortions. The sensitivity and specificity of the primary diagnostic tests, the fluorescent antibody test (FAT) and the microscopic agglutination test (MAT), used for the diagnosis of leptospirosis were also determined. For the 3 years, 74 (3.3%) of 2,264 abortion/stillborn submissions were diagnosed as leptospirosis. Twelve cases occurred in the 1991, 19 in the 1992, and 43 in the 1993 foaling seasons. Leptospires were isolated from 45 (60.8%) of the 74 cases, and they were identified as serovar kennewicki (43 cases), serovar grippotyphosa (1 case), and a serovar similar to pomona (1 case). Of the 29 culture-negative cases, serologic results indicated that leptospires in the Pomona serogroup (kennewicki is a member of this serogroup) were responsible for 25 abortions, leptospires in the Grippotyphosa serogroup for 1 abortion, and leptospires in the Sejroe serogroup for 1 abortion. The specificities of the FAT on fetal tissues and mare's placenta and of the MAT on fetal fluid were 100%. The sensitivity of the FAT was 98.7%, and that of the MAT was 81.3%. PMID- 7779972 TI - Use of commercial enzyme kits and fatty acid production for the identification of Serpulina hyodysenteriae: a potential misdiagnosis. AB - The accuracy of identification of Serpulina hyodysenteriae strains grown in a complex medium was 90% when 2 commercial test kits were used. Unlike the other S. hyodysenteriae strains, S. hyodysenteriae strain P35/2 was unusual in being indole negative. The nonpathogenic intestinal spirochete PWS/A, which is from a different species, was indole positive and alpha-galactosidase negative. Identification of these spirochetes on the basis of these kits alone would have been incorrect. The analysis of volatile fatty acids by gas chromatography showed that the ratio of acetic to butyric acid was from 11:1 to 44:1 for S. hyodysenteriae strains, which distinguished them from the other spirochetes. The exception was PWS/A (acetic: butyric of 32:1), but this spirochete, unlike the S. hyodysenteriae spirochetes, also produced isobutyric acid. Short chain fatty acid (SCFA) analysis by high-performance liquid chromatography detected different SCFAs in addition to acetic and butyric acids. These additional SCFAs did not contribute to further differentiation of the porcine spirochetes. PMID- 7779973 TI - Immunohistochemical detection of Tritrichomonas foetus in formalin-fixed, paraffin-embedded sections of bovine placenta and fetal lung. AB - An immunohistochemical technique using a monoclonal antibody was evaluated as a diagnostic tool to specifically label Tritrichomonas foetus in formalin-fixed, paraffin-embedded sections of placenta and fetal lung from bovine abortions. Trichomonads were demonstrated in tissues from each of 12 abortions due to T. foetus and none of 15 abortions due to other or unidentified causes. Moderate to marked background staining occurred only in severely autolyzed tissues from T. foetus-infected fetuses. The antibody faintly labeled 1 of 3 other species of trichomonads (Trichomonas gallinae) but did not label other protozoa, bacteria, or fungi tested. PMID- 7779974 TI - [The role of heme in activating rat myocardial guanylate cyclase by sodium nitroprusside]. AB - The basal activity of soluble rat myocardial guanylate cyclase (105000 x g supernatant) is stimulated by 2 mM dithiothreitol (2-fold). In the presence of 2 mM dithiothreitol, sodium nitroprusside enhances the enzyme activation up to 26.5 fold. Addition of heme-containing proteins (hemoglobin or myoglobin) produces further stimulation of the enzyme--by 44% and 69%, respectively. Ion-exchange chromatography of rat myocardial 105000 x g supernatant by stepwise elution with 50 mM Tris-HCl buffer pH 7.6 containing 0.22 M NaCl revealed two protein peaks (I and II), of which only peak II possessed the guanylate cyclase activity. The spectrum of the 105000 x g supernatant had an absorption maximum at 415 nm (Soret band) which disappeared from the spectrum of the protein peak II but was detected in the inactive protein peak I. The guanylate cyclase preparation (peak II) lost its ability to be activated by sodium nitroprusside. All the attempts to reconstitute the nitroprusside-induced activation of the enzyme by adding the inactive protein peak I or the heme-containing proteins (hemoglobin or myoglobin) to peak II were unsuccessful. The possible mechanism of rat myocardial guanylate cyclase activation by sodium nitroprusside is discussed. PMID- 7779975 TI - [Structure and biological properties of a conjugate of Bowman-Birk type soy proteinase inhibitor with a block copolymer of ethylene oxide and propylene oxide]. AB - The structure of the conjugate of Bowman-Birk soybean proteinase inhibitor (BBI) with the block copolymer of ethylene oxide and propylene oxide (proxanol) containing five moles of proxanol per mole of protein, has been studied. Data from reverse phase hydrophobic HPLC suggest that the conjugate is less hydrophobic compared to native BBI. A shift of the second derivative UV absorption spectrum for the conjugate towards the shortwave region indicates a greater accessibility of the Tyr-59 residue localized in the interdomain region of the BBI molecule for the solvent. It has been assumed that the conjugate induced increase in Ki for chymotrypsin may be due to both disturbances in the intact structure of the interdomain region of BBI and screening of the anti chymotrypsin reactive center as a result of hydrophobic interactions of propylene oxide blocks of proxanol with exposed hydrophobic groups around the reactive center. Supporting evidence in favour of BBI molecule hydrophilization as a result of modification by proxanol can be derived from decreased conjugate penetration into intestinal epithelial cells as well as from the slow elimination of the conjugate from mouse blood stream. PMID- 7779976 TI - [Adsorption of bile acids and cholesterol from model solutions and biological liquids modified with charcoal enterosorbents]. AB - Adsorption of some bile acids and cholesterol from simulated solutions and body fluids by medical carbons of different origin has been studied in order to elucidate the role of adsorption in cholesterol reduction as well as in prophylaxis and treatment of atherosclerosis by orally applied carbon adsorbents. Oxidized carbons modified by different metal cations were tested for the first time for their ability to correct the saline composition of body fluids. PMID- 7779978 TI - [The effect of energy metabolism inhibitors on phosphoinositide metabolism in peripheral nerve fibers]. AB - It has been established that inhibitors of the energy turnover acting on rat and rabbit sciatic nerves decrease the polyphosphoinositide level and reduce the 32P incorporation into these phospholipids. The results obtained are suggestive of the interaction between phosphoinositide and energy metabolisms in nerve fibers. PMID- 7779977 TI - [The role of nonparenchymal liver cells in activating protein synthesis in hepatocytes upon stimulating the mononuclear phagocyte system with lipopolysaccharide]. AB - It has been found that the rate of hepatocyte protein synthesis depends on the functional state of nonparenchymal liver cells (NPC), of Kupffer cells, in particular. When Kupffer cells were stimulated by intravenously injected lipopolysaccharide (LPS), zymosan or dextran sulfate, the rate of [14C]leucine incorporation into hepatic proteins increased 1.5-2-fold. Similar effects were observed in hepatocytes cocultured with NPC isolated from LPS-stimulated rats as well as in hepatocytes cultured in a conditioned medium from NPC treated with LPS, high density lipoproteins (HDL) and hydrocortisone. It is proposed that apoproteins of HDL resecreted by Kupffer cells may participate in the regulation of hepatocyte gene expression during stimulation of resident macrophages. PMID- 7779979 TI - [Supramolecular organization of erythrocyte glycolysis. I. Composition of the cytoplasm]. AB - The problems of supramolecular organization of glycolysis in human erythrocytes, molecular composition of the cytoplasm and putative forms of glycolysis organization have been reviewed. A hypothetical complex of glycolytic enzymes (metabolon) is discussed. Based on the molecular composition and experimental evidence, the maximally (approximately 1250) and minimally possible (approximately 30) numbers of the complexes per one cell as well as putative values of the "catalytic constant" for the metabolon have been estimated. PMID- 7779980 TI - [Supramolecular organization of erythrocyte glycolysis. II. Viscosity of the cytoplasm]. AB - Based on the molecular composition of the human erythrocyte cytoplasm, the contribution of each of the components (proteins, metabolites, electrolytes) in the overall values of the cytoplasm viscosity has been estimated. The viscosity of the human erythrocyte cytoplasm may be thought of as being determined by the protein component and is no less than 10 mPa.s at 37 degrees C. PMID- 7779981 TI - [Proteolytic processes in the rat brain and serum in hypokinesia and the adaptive effect of delta-sleep inducing peptide]. AB - It has been demonstrated for the first time that a single injection of the delta sleep inducing peptide (DSIP) results in long-term alteration of proteolytic enzyme activity within a broad range of pH. Using Ca(2+)-independent neutral endopeptidases from the synaptosomal fraction of rat brain and blood serum kallikrein as an example, it has been shown that DSIP activates limited proteolysis. This effect may contribute to the alteration of the set and "active" concentration of regulatory peptides and peptide hormones to the induction of the preadaptive state. DSIP also causes the redistribution of activity between Ca(2+) dependent and Ca(2+)-independent neutral endopeptidases associated with synaptosomal membranes, particularly under hypokinetic conditions. The significant decrease of the Ca(2+)-activated neutral proteinase I activity may be one of the mechanisms whereby the modulating effect of DSIP manifested as regulation of the number of glutamate receptors and limitation of effect of this excitatory neuromediator is realized under stress. Preliminary injection of DSIP prevents disturbances in the permeability of lysosomal membranes under long-term (24 hours) hypokinesia. PMID- 7779982 TI - [Biochemical mechanisms of resistance to a new antineoplastic agent amin(cyclopeptidylamin)-S-(-)-malatoplatinum (II) (cycloplatam)]. AB - The "in vivo" effect of cycloplatam on DNA synthesis in leukemia P388/o (parent strain), P388/c (cycloplatam-resistant strain) and in some organs of tumour bearing mice, such as spleen, kidney, gastrointestinal mucosa (GI mucosa) and bone marrow, has been studied. Cycloplatam induced a deep and stable inhibition of DNA synthesis in leukemia cells and kidney. DNA synthesis in normal dividing cells (GI mucosa, bone marrow, spleen) was shown to recover more rapidly than in leukemia cells and kidney after cycloplatam treatment. The GSH level was increased tenfold in leukemia P388/c cells in comparison with P388/o. The glutathione peroxidase and glutathione reductase activities were increased twofold in the resistant strain in comparison with the parent strain, while the activity of glutathione-S-transferase showed a 1.5-fold increase. Administration of cycloplatam to tumour-bearing mice caused a marked increase of the GSH level in the both leukemia strains. Alterations in GSH-dependent enzymes following cycloplatam therapy were expressed in a lesser degree. These data indicate that GSH and GSH-dependent enzymes may play an important role in the resistance of P388 leukemia cells to cycloplatam. PMID- 7779983 TI - [The effect of a chalone-containing fraction on passage of the S-phase of the cell cycle in regenerating liver]. AB - The duration and reversibility of the liver chalone-containing fraction on DNA synthesis in regenerating liver cells have been studied. It has been shown that administration of the [14C] chalone-containing fraction results in a rapid specific binding of the label to liver cells in which the label is retained for no less than 12 hours. The specific radioactivity of DNA in regenerating liver cells decreases 3-4-fold irrespective of the time of administration of the [14C] chalone-containing fraction. After repeated injections of the fraction under study, the hepatocytes loss their sensitivity towards this fraction. It is suggested that chalones exclude some part of the hepatocytes from the cell cycle which, in turn, leads to the asynchronous involvement in the cell cycle of a new hepatocyte population which is resistant to the chalone action. PMID- 7779984 TI - [Modulation of the level of sphingomyelin cycle products and expression of the CD3 receptor in immunocompetent organs by fumonisin B1]. AB - The fungi (Fusarium moniliforme) residing on cereals produce a broad range of mycotoxins, among which fumonisins display a high toxicity alongside with carcinogenic and teratogenic activities. Taking into account the ability of fumonisins to inhibit sphingolipid synthesis, the role of sphingomyelin cycle products in immune reactions was studied with the view of establishing the correlation between the expression of the surface receptor CD3 in immunocompetent organs (spleen, thymus) (T-cell mediated immunity) and the degree of sphingomyelin cycle activation (changes in the activities of sphingomyelinase and sphingomyelin and ceramide content) in the spleen, thymus and liver 2.5 hours after intraperitoneal injection of fumonisin B1 (FB1) (5 and 20 micrograms/animal). Significant sphingomyelinase activation was found in the thymus of animals injected with 20 micrograms of fumonisin. It coincides with a loss of the sphingomyelin and ceramide content. The changes in the sphingomyelinase activity and sphingomyelin content in the spleen and in the liver caused by fumonisin were insignificant, while the ceramide content dropped drastically. Fumonisin decreased the receptor CD3 expression on the surface of thymus cells "in vitro" and "in vivo", which is consistent with the sharp decrease of the ceramide content in this organ. Ceramide accumulation in thymus and spleen cells treated with sphingomyelinase in vitro correlates with the increased affinity of receptor CD3. The putative role of ceramide in the expression of receptors modulating T-cell mediated immunity under the influence of fumonisin is discussed. PMID- 7779985 TI - [Participation of SH-groups in regulating oxidative phosphorylation by malate and palmitate-uncoupled respiration in liver mitochondria]. AB - The effect of malate on respiration in liver mitochondria has been studied during oxidation of succinate in the presence of rotenone both in state 3 and after palmitate addition. Malate was shown to stimulate the rate of mitochondrial respiration in the both respiratory states, its effect being increased in the presence of the NAD-dependent substrates of oxidation-glutamate and pyruvate or thiols (cysteine and thiourea) Preincubation of mitochondria for 5 min in the absence of respiratory substrates eliminated the stimulating effect of malate. However, this effect was manifested in the conditions when the NAD-dependent respiratory substrates or thiols were added after preincubation of mitochondria. p-Chloromercuribenzoate eliminated the stimulating effect of malate. Carboxyatractyloside and ATP inhibited mitochondrial respiration in the presence of palmitate. Malate did not influence the action of the first effector but eliminated that of the second effector. It is concluded that malate can regulate oxidative phosphorylation and palmitate-uncoupled respiration by affecting the adenine nucleotide transported. The SH-groups localized outside the mitochondria in the hydrophilic region play an important role in the realization of malate effects. PMID- 7779986 TI - [Stability of a new product of oxidative stress in bacterial cells]. AB - Data on 32P-label incorporation with subsequent addition of non-radiolabelled o phosphate suggest that the new phosphorus compound, 2-C-methyl-D-erythritol-2,4 cyclopyrophosphate (MEC), accumulated in the cells of some bacterial species in response to oxidative stress does not rapidly exchange phosphorus with external o phosphate 3 hours after the introduction of its synthesis inducers into the Corynebacterium ammoniagenes culture. The accumulated MEC is retained in the cells despite the action of the cell wall synthesis inhibitor, chloramphenicol, or the energetic poisons, KCN and iodoacetate and also under anaerobic conditions. It has been shown that incubation of the cell-free lysate of a non induced culture, Micrococcus luteus, with MEC does not result in MEC hydrolysis; therefore, MEC accumulation after the redox-mediator addition is hardly due to the hydrolase inactivation but, rather, is due to the activation of the MEC synthesizing enzyme. The cells of C. ammoniagenes incorporate 32P from [32P]MEC but not 14C from [14C]MEC. This points to MEC hydrolysis prior to the uptake of its phosphoryl fragment by the cells. In this case 32P is found in the fractions differing by their position from MEC fractions. Experiments with sheep erythrocytes and mouse splenocytes revealed that MEC (10-100 micrograms per 1,000,000 splenocytes) does not influence the antibody production by these cells, whereas used at concentrations of 200-550 micrograms per 1,000,000 cells, MEC enhances the antibody production. However, while doing so, MEC causes the destruction of a considerable portion of splenocytes and sheep erythrocytes. PMID- 7779987 TI - Chalcone synthase localization in early stages of plant development. I. Immunohistochemical use of plasmolysis for localizing the enzyme in epidermal cell cytoplasm of illuminated buckwheat hypocotyls. AB - Immunohistochemical methods combined with progressive plasmolysis were used to localize chalcone synthase (CHS), an important enzyme for plant metabolism of aromatics in hypocotyls of illuminated buckwheat (Fagopyrum esculentum M.) seedlings. Illumination of etiolated seedlings with white light results in anthocyanin synthesis in the epidermal layer of the hypocotyl. Anthocyanin containing epidermal peels, after fixation for 30 min in 4% paraformaldehyde, 2.5% glutaraldehyde, 0.1% caffeine, were treated with a specific rabbit anti buckwheat CHS antibody and a 20 nm goat anti-rabbit IgG gold conjugate. CHS is specifically shown in epidermal cells as pink to dark red deposits. Progressive plasmolysis combined with our immunohistochemical method showed that CHS was located exclusively in the cytoplasm of the epidermal cells of buckwheat hypocotyls except for the guard cells, which contained no detectable CHS. PMID- 7779988 TI - A quick embedding method for light microscopy and image analysis of cotton fibers. AB - A quick embedding method using UV polymerization of methacrylate plastic has been devised for embedding fibers encased in a polyvinyl chloride tube. The resulting embedments are suitable for light microscopy and image analysis. PMID- 7779989 TI - Anti-fading agents for confocal immunofluorescence: colocalization of nuclear polypeptides. AB - We evaluated the performance of four anti-fading agents during acquisition of multiple optical sections near the widest diameter of Drosophila accessory gland nuclei using indirect immunofluorescence and confocal laser scanning microscopy. Two commercially available agents, Vectashield and SlowFade showed anti-fading properties that alleviated fluorochrome fading associated with the acquisition of multiple fluorescent optical Z-series from a single specimen by a confocal laser scanning system. Using these reagents, we were able to colocalize polypeptides through immunostained whole Drosophila nuclei. PMID- 7779990 TI - The influence of specimen preparation on artefacts in scanning electron microscopy of respiratory cilia. AB - The effects of various handling procedures used in preparing specimens of human and pig respiratory mucosa for scanning electron microscopy (SEM) were studied. Using five different washing methods, the percentage area of mucosa covered with extracellular material varied from 1.5 to 53.1%. The best results were achieved when specimens were washed by gently inverting a sample 30 times in a container filled with physiological saline. Fixation and drying of the surface layer caused disorientation of cilia and made examination difficult. Mechanical damage caused loss of cilia and rupture of the cell membrane. For SEM of respiratory cilia it is important to wash the specimen in saline before fixation and to use biopsy forceps as little as possible. PMID- 7779991 TI - Silver enhancement of colloidal gold particles in deplasticized semithin epoxy sections. AB - A simple method for light microscope screening of pre-embedded, gold-labeled samples, by silver enhancing deplasticized semithin epoxy sections is presented. This method is of great help in visualizing the topography of gold labeled sites at low magnification and for selecting labeled sample regions for subsequent electron microscope analysis on serial ultrathin sections. The method was developed during a study of lectin binding sites on the egg surface of the anuran amphibian Discoglossus pictus. PMID- 7779992 TI - Intracytoplasmic sperm injection in the mouse. AB - Intracytoplasmic sperm injection (ICSI) was successful in the mouse when a piezo driven micropipette was used instead of a mechanically driven conventional pipette. Eighty percent of sperm-injected oocytes survived, and approximately 70% of them developed into blastocysts in vitro. When 106 embryos at the 2- to 4-cell stage were transferred to eight naturally mated foster mothers, 30% of the embryos (25-43%, depending on the host) reached the full term. Except for two that were cannibalized soon after birth, all of the young (30 pups) grew into normal adults. Studies of this type on the mouse may increase understanding of the fertilization process and of how ICSI works. PMID- 7779993 TI - Influence of the muscarinic agonist carbachol on intracellular Ca2+ in chicken granulosa cells: I. Dependence on follicular maturation. AB - The present study addressed the influence of follicular development on carbamylcholine chloride (Cch)-induced Ca2+ transients and inositol 1,4,5 trisphosphate (IP3) production in granulosa cells isolated from the first (F1), third (F3), and fifth and sixth (F5,6) largest follicles. Intracellular free calcium, [Ca2+]i, was measured in fura-2-loaded cells about 20-36 h after their isolation. The percentage of cells responding to a maximal stimulatory concentration of Cch (0.2 mM) was higher in the F1 (89%) granulosa cells than in cells from the F3 (68%) and the F5,6 (72%) follicles. Most of the Ca2+ transients that were elicited in F1 granulosa cells were characterized by large (696 +/- 119 nM), fast (260 +/- 55 nM/sec) increases in [Ca2]i followed by a slow, uneven decrease in [Ca2+]i to the resting concentration. In contrast, Cch-induced changes in [Ca2+]i in F3 and F5,6 granulosa cells were generally both smaller (154 +/- 37 nM and 165 +/- 37 nM, respectively) and slower (36 +/- 25 nM/sec and 46 +/- 16 nM/sec, respectively) than those observed in cells from the largest follicle. Removal of external Ca2+ did not alter the large, fast increases in [Ca2+]i; however, it nearly blocked the slow responses observed in F3 and F5,6 cells. IP, production was elevated in 3H-myo-inositol-loaded F1 granulosa cells after 1 min of Cch (0.2 mM) treatment, whereas inositol bisphosphate (IP2) production and inositol monophosphate (IP) production were elevated only after longer incubations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779994 TI - Mitochondrial deoxyribonucleic acid 4977-bp deletion is associated with diminished fertility and motility of human sperm. AB - The accumulation of mitochondrial DNA (mtDNA) mutations has been suggested to be an important contributor to human aging and degenerative diseases. In previous studies, we found an age-dependent increase of mtDNA mutations in various human tissues. Sperm motility is one of the determinants of male fertility. The possible relationship between mtDNA deletions and diminished fertility and motility of sperm was explored in the present study. We examined accumulation of the 4977-bp mtDNA deletion in spermatozoa obtained from patients with infertility or subfertility and compared these values with those of normal individuals. Using polymerase chain reaction (PCR) techniques, we determined the frequency of occurrence and the proportion of mtDNA with the 4977-bp deletion in human spermatozoa with different motilities. Human spermatozoa were separated by self migration in Percoll gradients into five fractions with different motility scores. The highest frequency of occurrence of the 4977-bp mtDNA deletion was found in sperm in the fraction with the lowest motility. The results revealed a negative correlation between sperm motility and the proportion of 4977-bp-deleted mtDNA. Furthermore, we found a significantly higher incidence of the 4977-bp mtDNA mutation in patients with asthenospermia, oligospermia, and primary infertility compared to normal individuals. These findings suggest that mtDNA mutations may play an important role in some pathophysiological conditions in human spermatozoa. PMID- 7779995 TI - Prostaglandin synthase activity of fetal sheep cotyledons at 122 days of gestation and term: expression of prostaglandin synthetic capacity in fetal cotyledonary tissue near labor is location-dependent. AB - An activity assay is described quantification of prostaglandin synthase (PGHS) in sheep placental cotyledon under initial velocity conditions through measurement of the stable product prostaglandin E2 (PGE2). The effects of temperature, time, and substrate concentration on initial reaction velocity, and lipoxygenase and PGHS product formation in cotyledonary tissue, were examined in detail. We used this activity assay to determine whether or not an increase of active PGHS by placental location within the uterus might contribute selected prostaglandins (PG) for the directed initiation of parturition. Sheep cotyledon tissue was collected (n = 6 animals) from the ventral aspect of the uterine body, mid-horn, and horn tip at 122 days of gestation (dga), and from the same locations in the ventral body and horn tip at 142-145 dga (in animals at term but not in labor; n = 4). At 122 dga, there was no increase in active PGHS in cotyledonary tissue from the horn tip, mid-horn, or uterine body. By 142-145 dga, the horn showed significantly (p < 0.01) more enzyme activity than the body. At the same time, production of PGE2, expressed as a percentage of total eicosanoids, had not changed significantly. The development of an increase in PGHS toward the uterine tip implies that variations in regional PG production may contribute to the progression of labor. PMID- 7779996 TI - Tumor necrosis factor alpha inhibits rat granulosa cell plasminogen activator activity in vitro during follicular development. AB - The objective of the present in vitro study was to examine the potential modulatory influence of tumor necrosis factor-alpha (TNF alpha) on the granulosa cell plasminogen activator (PA) system during follicular development. Undifferentiated and differentiated rat granulosa cells of preantral follicles and antral follicles, respectively, were cultured in a chemically defined medium with or without TNF alpha and in the absence or presence of FSH (400 ng/ml). TNF alpha (0.5-50 ng/ml) inhibited basal and FSH-induced net PA activities in cultures of granulosa cells from preantral and antral follicles in a concentration- and time-dependent manner. Although PA activities with corresponding molecular masses of 55 kDa and 30 kDa (tissue-[tPA] and urokinase [uPA] type PA, respectively) were observed in culture of undifferentiated granulosa cells, only tPA was detectable in differentiated cells. Concomitant to the stimulation in PA activities by FSH was a marked increase in progestin secretion and a decrease in DNA synthetic capacity at both stages of follicular development. Independent of the differentiative state of the granulosa cells, TNF alpha suppressed FSH-stimulated tPA activity, but potentiated FSH-induced uPA activity in undifferentiated granulosa cells. The inhibition of the gonadotropin action by TNF alpha was accompanied by an increase in PA inhibitor activity, which was more pronounced in cultures of differentiated granulosa cells. TNF alpha inhibited FSH-induced progestin secretion and reversed the action of the gonadotropin on DNA synthesis irrespective of stage of follicular maturation. These studies demonstrate that TNF alpha modulates gonadotropic action on granulosa cell differentiation (PA and progestin secretion) and proliferation (DNA synthesis) during follicular development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7779997 TI - Parthenogenetic activation of porcine oocytes with guanosine-5'-O-(3' thiotriphosphate). AB - A possible mechanism by which sperm activate oocytes may involve a G protein mediated signal-transducing pathway. Artificial stimulation of G proteins leads to events very similar to those at fertilization in oocytes of several species. Here we report the effects of activation of a G protein with guanosine-5'-O-(3' thiotriphosphate) (GTP-gamma-S), a hydrolysis-resistant analog of guanosine triphosphate (GTP), in porcine oocytes. Mature oocytes were injected with 1 mM GTP-gamma-S. In response to injection, oocytes underwent changes normally occurring at fertilization, i.e. cortical granule exocytosis, changes in the protein synthetic profile, pronuclear formation, and development to the blastocyst stage. Guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S; a metabolically stable analog of guanosine diphosphate [GDP] that inactivates the G protein) and the carrier medium (CM; medium in which the injected compounds were dissolved) were significantly less effective in oocyte activation. It is suggested that porcine oocytes contain the components of a G protein-mediated signaling pathway that might function in oocyte activation at fertilization. PMID- 7779998 TI - Effects of matrix proteins and heparin-binding components in fetal bovine serum upon the proliferation of ectoplacental cone cells in mouse blastocysts cultured in vitro. AB - Trophoblastic invasion of the endometrium is among the events that are crucial for successful implantation and hemochorial placentation. To understand the mechanism underlying the trophoblastic invasion, we investigated effects of fibronectin substratum and heparin-binding components in fetal bovine serum (FBS) upon trophoblast and ectoplacental cone (EPC) cells derived from mouse blastocysts produced by IVF and cultured in vitro. The results demonstrated that 1) in these blastocysts, contact of EPC cells with fibronectin-coated glass substratum in the presence of FBS triggered an outburst of cell proliferation with the eventual differentiation of the EPC cells into secondary giant trophoblast cells and 2) frequencies of blastocysts that exhibited EPC cell proliferation significantly increased if FO medium (modified Eagle's minimum essential medium) was supplemented with FBS depleted of heparin-binding substances (H-FBS). One possible interpretation of the effect of H-FBS is that free fibronectins or related substances in the serum might interfere with EPC cell proliferation, for which the presence of substratum-bound fibronectin is essential. Alternatively, the serum might contain heparin-binding competitive inhibitors of yet unidentified growth factor(s) necessary for EPC cell proliferation. PMID- 7779999 TI - Influence of follicular maturation on inhibition of luteinizing hormone-, cyclic 3',5'-adenosine monophosphate-, and forskolin-stimulated progesterone production in chicken ovarian granulosa cells exposed to bursal anti-steroidogenic peptide. AB - Previously, we demonstrated that a peptide from chicken bursa of Fabricius, bursal anti-steroidogenic peptide (BASP), inhibited LH-stimulated progesterone biosynthesis by granulosa cells from the two largest preovulatory follicles of the chicken ovary. In the present study, we investigated the influence of follicular maturation on the ability of BASP to inhibit granulosa cell steroidogenesis. Granulosa cells from the largest (F1), third largest (F3), and fifth largest (F5), preovulatory follicles of the laying hen were exposed to BASP in the presence or absence of ovine LH, forskolin, or dibutyryl-cAMP (db-cAMP). BASP (0.125 or 0.25 bursal equivalents [BEQ]) suppressed basal progesterone production in F5, but not in F1 or F3, granulosa cells. BASP suppressed LH stimulated progesterone production in F1, F3, and F5 granulosa cells in a concentration-dependent manner; however, the lowest level (0.06 BEQ) did not suppress progesterone production in F5 granulosa cells. All levels of BASP suppressed forskolin-stimulated progesterone production in F1 granulosa cells, but only the highest level (0.25 BEQ) inhibited forskolin-stimulated steroidogenesis in F3 and F5 granulosa cells. Similar results were obtained with db-cAMP-stimulated granulosa cells. The inhibitory effects of BASP on F1, F3, and F5 granulosa cells were directly compared on a percentage basis. In the presence of each secret-agogue, the lowest level (0.06 BEQ) of BASP effectively suppressed progesterone synthesis in F1 and F3 but not F5 granulosa cells. At higher levels, there was no consistent difference in the ability of BASP to suppress stimulated progesterone production in granulosa cells at different stages of maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780000 TI - Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea. AB - Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morpho-regulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7780001 TI - Expression of mitochondrial heat shock protein 60 in distinct cell types and defined stages of rat seminiferous epithelium. AB - Changes in the level of the gene transcript of heat shock protein (hsp)60, a mitochondrial chaperonin, during the cycle of rat seminiferous epithelium and its cellular localization were studied. The seminiferous epithelium showed a cell type-specific expression of hsp60. Immunostaining of adult rat testis revealed localization in Sertoli and Leydig cells. In germ cells, mitochondria of spermatogonia and early primary spermatocytes were immunoreactive for hsp60. Mitochondria of all other germ cell types were completely negative for hsp60. Stage-specific expression of hsp60 was determined from pooled segments of stage specific microdissected tubules by a combination of Western blotting and polymerase chain reaction (PCR). High concentrations of hsp60 were found in stages I-V and IX-XIV, and low levels were detected in the other stages, i.e., VI VIII. In stages with high hsp60 expression, spermatogonia divide mitotically, whereas in stages lacking mitosis, the hsp60 level was much weaker. In seminiferous epithelium, two different types of mitochondria are present. Therefore, immunoelectron microscopy was used to differentiate these two morphologically distinct types of mitochondria. The crista type of mitochondria (e.g., in Sertoli cells and spermatogonia) reacted with the antibody against hsp60, whereas hsp60 was negative in so-called "condensed"-type mitochondria found in midpachytene spermatocytes and more advanced germ cells. It could be shown for the first time that expression of the hsp60 gene is regulated during the cycle of the seminiferous epithelium. The results indicate that the gene product is primarily needed during the initial steps of spermatogenesis in which most of the cell divisions occur, while its expression during the differentiation of spermatids and sperm is obviously not necessary. The presence of hsp60 in stages with mitotic activity suggests a very active mitochondrial protein import and protein assembly machinery that generates further mitochondria for the dividing cells. PMID- 7780002 TI - Modulation of gonadotropin secretion at the pituitary level by testosterone in gonadotropin-releasing hormone-treated male rats during food deprivation. AB - Testosterone (T) inhibits the synthesis and secretion of FSH and LH by decreasing the secretion of GnRH from the hypothalamus. However, T is also able to stimulate FSH gene expression and synthesis at the pituitary level when the release or action of GnRH is blocked. In the present study, we analyzed whether the positive effect of T on pituitary FSH could also be brought about during food restriction, which represents a model of suppressed GnRH secretion. We also wanted to learn whether this positive effect could be detected if GnRH pulsatility is maintained by exogenous injections. Adult male rats were subjected to various combinations of the following treatments: 1) implantation of silastic capsules containing T for Days 0-4 of the experiment, 2) starvation for Days 1-4 of the experiment, and 3) GnRH-treatment at 2-h intervals (500 ng/kg BW) for Days 3-4. The combined treatments were as follows: 1) control, 2) only starvation, 3) only GnRH, 4) starvation+GnRH, 5) only T, 6) starvation+T, 7) GnRH+T, and 8) starvation+GnRH+T (n = 12/group; two independent experiments). Serum FSH level was decreased 20% by starvation (p < 0.01), but no decrease was observed when the starving animals were treated with T. GnRH treatment increased serum FSH in both ad libitum-fed and starving animals to 266% and 333% of the respective control values (both p < 0.01). When T was added to these treatments, the increases in serum FSH were smaller, 219% and 272%, respectively (p < 0.01 vs. respective groups without T).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780003 TI - Daily patterns of pituitary prolactin secretion and their role in regulating maternal serum progesterone concentrations across pregnancy in the Djungarian hamster (Phodopus campbelli). AB - Profiles of serum prolactin (PRL) and progesterone (P4) were determined in repeatedly (every 2 h) sampled female Djungarian hamsters (Phodopus campbelli) over a 24-h period on Days 3, 6, 9, 12, and 15 of the 18-day pregnancy. The first half of pregnancy was characterized by significant surges of PRL within a 2-h period around dawn (0500 h) and dusk (1900 h), with some females also showing a weak midday surge at 1300 h. By Day 9, dusk and midday surges were absent, but the dawn surge remained at its initial amplitude. On Day 12, no PRL surges were seen. Resumption of both the dusk and dawn PRL surges occurred on Day 15 of gestation. Considerable interindividual variability in the amplitude of PRL surges, the timing of PRL surges, and the number of surges per day was detected and would complicate any assessment of PRL levels based on single samples per female. Serum P4 concentrations were 8-10 ng.ml-1 before doubling on Day 15. A 3 day treatment of 50 and 300 micrograms bromocryptine (CB 154; on Days 13-15) effectively suppressed PRL during late pregnancy (Day 15) but did not alter serum P4 concentrations or interfere with parturition. Therefore, surges of PRL are not an essential luteotropic stimulus during late gestation. Compared to oil-injected controls, CB 154-treated females had a higher incidence of infanticide postpartum. Growth rates of the pups, mammary gland development, and successful delivery of milk to pups, however, did not differ between groups. Further studies will be required to determine the function of late-gestation PRL surges. PMID- 7780004 TI - Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect? AB - A guinea pig model was used to study the hormonal control of uterine leiomyomas. Twenty female guinea pigs were divided into four groups--young, old, ovariectomized (OVX), and non-OVX animals--and were given two estradiol-17 beta (E2) silastic implants each for 3-10 mo; another four older OVX animals served as controls and received empty implants. After 3 mo, 100% (8 of 8) of the OVX animals, but none of the OVX controls, developed tumors, mainly on the uterine serosa and the abdominal wall. Electron microscopy and desmin immunostaining demonstrated that the tumors were leiomyomas. In E2-treated animals, E2 levels in serum, leiomyomas, or leiomyoma-free uterine segments rose significantly while serum progesterone (P4) was negligible. Surprisingly, only 8% (1 of 12) of the non-OVX animals developed a tumor. This apparent "ovarian protection" was transient: after 6-9 mo, 50% of the remaining non-OVX animals developed leiomyomas, but these were smaller and fewer than in OVX animals. On the basis of this model, we propose the hypothesis that some factors from the ovaries suppress leiomyoma growth in response to estrogen but that as the ovaries age this protection is diminished, allowing the clinical development of leiomyomas. PMID- 7780005 TI - Influence of prenatal and postnatal photoperiods on postnatal testis development in the Siberian hamster (Phodopus sungorus). AB - In Siberian hamsters, juvenile testicular development is regulated to a large extent by photoperiod. Mother hamsters are able to pass photoperiodic information to their male fetuses, and this information can influence their postnatal gonadal development. In this study, we investigated the effects of gestation in long (16L:8D) and short (10L:14D) day lengths on the rates of juvenile testicular growth in several different postnatal photoperiods. On the day of parturition, parents and young from each gestation photoperiod were raised in 14L:10D through Day 13 of life and then were exposed to one of six photoperiods--16L:8D, 15L:9D, 14L:10D, 13L:11D, 12L:12D, or 10L:14D--until Day 32 of age. The data indicated that 15L and 14L are the minimal day lengths required to prevent complete inhibition of testis growth in long (16L) and short day (10L)-gestated hamsters, respectively. These results support earlier findings suggesting that gestation photoperiod can influence the rate of reproductive development in a certain range of "intermediate" postnatal day lengths (14L to 15L), but that gestation photoperiod does not alter the pattern of testis development in hamsters exposed to other (i.e., longer or shorter) postnatal photoperiods. Thus, both the absolute length and the direction of change of photoperiods experienced in early life can influence prepubertal testis growth. PMID- 7780006 TI - Interleukin 4 production by human amnion epithelial cells and regulation of its activity by glycosaminoglycan binding. AB - The pro-inflammatory molecules, tumor necrosis factor alpha (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and prostaglandin E2 (PGE2), are postulated to have a role in human pregnancy and parturition. The ability of interleukin 4 (IL-4) to suppress the production of TNF alpha, IL-1, IL-6, and PGE2 by activated monocytes prompted us to investigate a possible regulatory role for IL-4 in human gestation. Immunohistochemical techniques were used to show that human amnion epithelium stained positively for IL-4. Tissue from both the first (n = 5) and third (n = 46) trimester expressed immunoreactive IL-4, which was detected by the use of four antihuman IL-4 monoclonal antibodies. Analysis of mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA extracts of amnion epithelial cells indicated that they were the source of IL-4. One of the anti-IL-4 antibodies used stained IL-4 protein associated with the basement membrane of the amnion epithelium. The mechanism of this association was investigated. IL-4 was shown to be a heparin-binding cytokine, which would enable it to bind to components of the extracellular matrix. Thus, this study identified a previously undescribed cellular source of IL-4, implicating a role for IL-4 in human gestation. Additionally, glycosaminoglycan binding may regulate IL-4 activity in vivo. PMID- 7780007 TI - Secretion of bovine uterine proteins in response to type I interferons. AB - Bovine interferon-tau (bIFN-tau) is secreted by the developing conceptus and initiates antiluteolytic events by interacting with uterine membrane receptors. We have identified three endometrial proteins (approximately 8, 16, and 28 kDa; P8, P16, and P28; respectively) that are secreted in response to recombinant (r) bIFN-tau. The objective of this study was to determine whether or not secretion of these proteins was a unique response to IFN-tau during early pregnancy. Three experiments were designed to examine secretion of endometrial proteins as a function of time in culture (0, 3, 6, 12, 18, 24 h), stage of the estrous cycle and pregnancy (Days 15, 18, 0/21), and dose of Type I IFN (0, 0.5, 5, and 25 nM; rbIFN-tau, rbIFN-alpha, and roIFN-tau). Endometrium was cultured for times specified with L-[3H]leusine to generate radiolabeled proteins. Secreted proteins were quantitated by using one-dimensional (1D)-PAGE, fluorography, and densitometry. Secretion of P8, P16, and P28 increased over time (p < 0.0001) in culture and in response to 25 nM rbIFN-tau (p < 0.05). Secretion of P8 in response to rbIFN-tau was higher (p < 0.05). Secretion of P8 in response to rbIFN tau was higher (p < 0.0005) in endometrium collected from pregnant than nonpregnant heifers, but did not differ across the days examined. Although secretion of P8 was higher (p < 0.0001) in the presence than in the absence of rbIFN-tau, it was not affected by rbIFN-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780008 TI - Progesterone, estradiol, and prolactin involvement in lactation, including lactation following a postpartum mating, in the Djungarian hamster (Phodopus campbelli). AB - The endocrinology of lactation in the Djungarian hamster was investigated through once-daily sampling of females on Days 0, 3, 6, 9, 12, 15, and 18 postpartum. Serum prolactin (PRL) was elevated during early lactation but declined with time. Serum progesterone (P4) levels were uniformly low, and serum estradiol (E2) levels increased after Day 9. New CL were formed after the postpartum ovulation and persisted throughout lactation. During the first 9 days, the CL had the high P4 content typical of pregnancy. After Day 9, each individual CL decreased in P4 content and increased in E2 content. As evidenced by the reappearance of large antral follicles, lactating females probably returned to ovulatory cycles at about that time. The Djungarian hamster has a postpartum estrus and is capable of delivering a second litter without a diapause (18 days), although the majority of second litters are delayed. Mating during the postpartum estrus had no detected effect on growth or survival of the first litter. Second pregnancies were developmentally delayed by 3 to 7 days. P4 was effectively absent from serum for the first 12 days after mating. Although CL contained high levels of P4, the CL remained small and poorly vascularized. Mated females did not have higher serum P4 levels than nonpregnant, lactating females until Day 18. In response to the competing demands of lactation and concurrent gestation, the endocrine conditions associated with pregnancy were the most affected. PMID- 7780009 TI - In vitro transformation of rabbit cytotrophoblast cells into syncytiotrophoblast: stimulation of hormone secretion by progesterone and dibutyryl cyclic 3',5' adenosine monophosphate. AB - Rabbit placenta syncytiotrophoblast cells exhibit immunostaining for the hormone relaxin. The objectives of this study were to evaluate the ability of cultured rabbit trophoblast cells to secrete immunoreactive (IR) relaxin and then to study the effects of progesterone, which is essential for maintenance of the placenta and of pregnancy in the rabbit, on that secretion. On Day 1, both treated and untreated trophoblast cell cultures consisted of 90% relaxin-negative mononuclear cells (cytotrophoblast and fibroblast) and 10% relaxin-positive multinuclear cells (syncytiotrophoblast). Media from untreated cultures, collected throughout 9 days of culture, contained low but constant levels of relaxin. Electron microscopy studies indicated that relaxin was localized in dense granules of the multinuclear cells and that these cells formed by fusion of mononuclear cytotrophoblast. Progesterone treatment (40 and 80 ng/ml) increased (p < 0.0001) media concentrations of relaxin, increased the number of desmosomes between cytotrophoblast cells (12 vs. 4 for controls on Day 5), and increased the percentage of multinuclear cells (73% of the cell population vs. 20% for controls on Day 7). Specificity of the progesterone effect was evaluated by treatment of cultures with dibutyryl cAMP (dbcAMP), insulin, hCG, estradiol-17 beta, prostaglandin E2, and prostaglandin F2 alpha. Only dbcAMP (2 mM and 4 mM) produced an increase (p < 0.0001) in media concentrations of relaxin. These results indicate that, like the intact placenta, cultured cytotrophoblast cells fuse to form syncytiotrophoblast and that the latter contain IR relaxin. PMID- 7780010 TI - Effects of passive immunization of ewes against an inhibin-peptide on gonadotropin levels, ovulation rate, and prolificacy. AB - The experimental objectives were to determine whether injection of semi-purified (sp; ammonium sulfate-precipitated) and highly purified (hp; immunoaffinity purified) ovine antibody (Ab) against an inhibin-peptide fragment (alpha-IF) before the preovulatory period would 1) stimulate FSH secretion in a dose response manner, 2) induce an increase in ovulation rate, and 3) affect pregnancy rate and prolificacy (lambs born alive per ewe lambing). During the early breeding season, estrus was synchronized in 30 2-yr-old crossbred ewes through use of progesterone-releasing pessaries (CIDR-G). Two doses (330 and 660 laboratory reference preparation [RP-2] kU) of sp- and hp-alpha-IF-Ab were injected i.m. 48 h before CIDR-G removal (6 ewes per group). Six other ewes received control solution. Plasma alpha-IF-Ab titers peaked at 12 h postinjection. Plasma FSH levels were higher (p < 0.02) in alpha-IF-Ab-treated ewes than in control ewes from 12 to 24 h postimmunization. Magnitudes of FSH increases were similar in ewes administered sp- and hp-alpha-IF-Ab and were greater (p < 0.05) in ewes receiving 660 than in those receiving 330 RP-2 kU. Compared to control values, the higher alpha-IF-Ab dose increased FSH levels by 44 +/- 5% and the lower dose increased the levels by 22 +/- 3%. Plasma LH levels were similar among passively immunized and control sheep. Ovulation rate was increased (p < 0.0005) by alpha-IF-Ab treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780011 TI - Expression of collagen alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains in the pregnant mouse uterus. AB - The alpha 1, alpha 2, and alpha 3 chains of collagen VI and mRNAs for these chains were localized in the female mouse reproductive tract by immunofluorescence and in situ hybridization. High levels of collagen VI protein and mRNAs were present in the endometrium and myometrium of the uterus up to Day 4.5 of pregnancy. After embryo implantation, reduction in collagen VI protein within the decidualizing endometrium correlated with significantly reduced steady state levels of alpha 1(VI), alpha 2(VI), and alpha 3(VI) mRNAs, indicating either transcriptional down-regulation of collagen VI gene expression or decreased stability of transcripts. High levels of alpha 1(V1) and alpha 2(VI) mRNAs, but not alpha 3(VI) mRNA, in cells surrounding the uterine epithelium in the mesometrial region did not correlate with deposition of collagen VI protein in this region. These data are consistent with an important role of alpha 3(VI) in assembly of collagen VI heterotrimers. However, distinct immunostaining with antiserum to alpha 2(VI) chains in the extracellular matrix immediately beneath the uterine epithelium may indicate that alpha 2(VI) chains are deposited without the alpha 1(VI) or alpha 3(VI) collagen chains. No collagen VI protein or mRNAs were detected in any tissue layers of the embryo on Days 5.5 or 6.5 of gestation. PMID- 7780012 TI - Induction of precocious germinal vesicle breakdown (GVB) by GVB-incompetent mouse oocytes: possible role of mitogen-activated protein kinases rather than p34cdc2 kinase. AB - In contrast to fully grown mouse oocytes, growing oocytes released from their preantral follicles are not capable of resuming meiosis spontaneously. However, when these denuded growing oocytes are incubated for 2-3 days in control medium and then treated with okadaic acid, 95% undergo precocious germinal vesicle breakdown (GVB) and chromosome condensation within 24 h. This study shows that both events apparently occur through a p34cdc2 kinase-independent pathway, since activity of this kinase was detected only after the oocytes had undergone okadaic acid-stimulated GVB. In contrast, microtubule-associated or mitogen-activated protein (MAP) kinases 1 and 2 were activated before GVB and their level of activity was correlated with the percentage of oocytes undergoing GVB, suggesting that these kinases may promote GVB and chromosome condensation under these experimental conditions. In addition, it is shown that MAP kinases accumulate during normal oocyte growth in vivo, but not in cultured denuded oocytes in vitro even when these oocytes become competent to undergo okadaic acid-stimulated GVB. Unlike p34cdc2, the accumulation of MAP kinases requires close physical interactions between the oocytes and the granulosa cells but is not necessary for the oocyte to become GVB-competent. Therefore, it MAP kinases are actually involved in the induction of GVB and chromosome condensation during normal oocyte maturation, acquisition of GVB competence requires oocyte-autonomous accumulation of MAP kinase activator(s) rather than the MAP kinases themselves. PMID- 7780013 TI - Monoclonal antibody directed to Le(y) oligosaccharide inhibits implantation in the mouse. AB - We investigated the role of carbohydrates in blastocyst attachment to the uterine epithelium. Le(y) (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3] GlcNAc) was localized by indirect immunofluorescence to the surface of the mouse blastocyst and uterine epithelium. Western blot analysis showed that Le(y) is carried on many uterine glycoproteins in both pregnant and nonpregnant females; however, new species were detected on Day 4 postcoitum (p.c.) coincident with the onset of uterine receptivity. The function of Le(y) in implantation was tested by injecting monoclonal antibody (mAb) directly into the uterine lumen on Days 3-5 p.c. The effects of intrauterine injections on implantation were scored by comparing the number of viable embryos to the number of CL on Day 10 p.c. Injection of purified anti-Le(y) IgM into the uterine lumen on the afternoon of Day 4 significantly inhibited implantation. This effect was dose-dependent and was obtained during a narrow time window, from 87 to 93 h p.c. Inhibition of implantation was not observed in contralateral uterine horns injected with saline, nor was it observed in uterine horns injected with other anti carbohydrate mAbs. We conclude that binding of anti-Le(y) to the blastocyst or luminal epithelium masks a ligand involved in implantation. Although the mechanism of inhibition is unknown, we show that Le(y) can interact with another oligosaccharide (H) that has been described as a possible uterine ligand for blastocyst attachment. We hypothesize that Le(y) and H form carbohydrate carbohydrate interactions that promote close apposition of cell surface membranes during an early step in implantation. PMID- 7780014 TI - Atresia in follicles grown after ovulation in the pig: measurement of increased apoptosis in granulosa cells and reduced follicular fluid estradiol-17 beta. AB - The incidence of atresia in the first group of follicles grown after ovulation was investigated in the pig. At slaughter, 113 follicles 3-6 mm in diameter were dissected from the ovaries of four pregnant pigs per day on Days 5, 6, and 7 after the onset of estrus. Granulosa cells were isolated from each follicle. The percentage of granulosa cells containing sub-diploid amounts of DNA (%Ao cells), a measure of apoptosis, was determined for each follicle by DNA fluorescence flow cytometry of propidium iodide (PI) stained nuclei of ethanol-fixed cells. Granulosa cell DNA condition was used to classify follicles. Follicles with > or = 10% Ao cells (n = 33) were designated biochemically atretic (BA), and follicles with < 10% Ao cells (n = 80) were designated biochemically healthy (BH). Internucleosomal cleavage, also indicative of apoptosis, was determined by autoradiographic analysis of [32P]-3'-end-labeled DNA from granulosa cells. Densitometric analysis showed that optical density of [32P]-3'-end-labeled DNA fragments in the 0.18-20-kb size range was correlated with the %Ao cells (R > or = 0.90, N = 22, p < 0.001). The incidence of pigs with BA follicles was 2 of 4, 3 of 4, and 4 of 4 on Days 5, 6, and 7, respectively. The %BA follicles per pig (mean +/- SEM) increased (p < or = 0.01) between Days 5 and 7; values were 6.2 +/ 3.6, 28.1 +/- 13.5, and 50.0 +/- 7.1, respectively, on Days 5, 6, and 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780016 TI - Sperm pairing in the opossum increases the efficiency of sperm movement in a viscous environment. AB - In order to understand why sperm pairing has evolved in most American marsupials, the movement parameters of spermatozoa from Monodelphis domestica were analyzed after incubation in capacitating medium for 15 min, 2 h, and 24 h to induce a proportion of sperm pairs to uncouple. Motility characteristics of paired and single spermatozoa were measured in media of differing composition and viscosity by means of computer-aided semen analysis. In minimum essential medium or in RPMI 1640 medium alone, the absolute mean straight-line and curvilinear velocity values of paired spermatozoa (342 +/- 34 and 361 +/- 19 microns/sec, respectively, at 37 degrees C) were significantly greater than those of single spermatozoa (247 +/- 14 and 319 +/- 16 microns/sec), while mean lateral head displacement for paired spermatozoa (5.6 +/- 2.1 microns) was significantly less than for single spermatozoa (11.4 +/- 2.6 microns). However, when medium was made more viscous with polyvinyl pyrrolidone (0.8-82 poise) and sperm motility was calculated as a percentage of maximum attained velocity (in medium alone), there was no significant difference in straight-line or curvilinear velocity for single or paired spermatozoa in medium of the lowest viscosity (0.8 poise). In contrast, paired spermatozoa in medium of higher viscosity (above 1.92 poise) maintained straight-line velocity (e.g., 54 +/- 3% of maximum straight-line velocity in medium of 2.28 poise) while single sperm moved in tight circles and exhibited poor straight-line velocity (5 +/- 1% of maximum velocity). The data show that paired spermatozoa exhibit a significant motility advantage over single spermatozoa in a viscous medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780015 TI - Progesterone secretion and proliferation in cultured rabbit granulosa cells under conditions of beta-D-xyloside-induced inhibition of proteoglycan synthesis. AB - Proteoglycans present in follicular fluid are synthesized by granulosa cells under gonadotropin control. An inhibitor of proteoglycan synthesis, p-nitrophenyl beta-D-xyloside (beta-D-xyloside) was used as a probe to study rabbit granulosa cell steroidogenesis and proliferation under abrogated proteoglycan synthesis. Granulosa cells isolated from rabbit preovulatory follicles were cultured 24 h in Minimum Essential Medium plus 2.5% fetal calf serum in the presence or absence of beta-D-xyloside and were then treated with FSH or dibutyryl cAMP (db-cAMP) alone or in combination with beta-D-xyloside for a further 24 h. The exposure for 48 h of granulosa cells to 1 mM beta-D-xyloside in the absence or presence of FSH inhibited proteoglycan synthesis and increased the amount of glycosaminoglycans (GAG). FSH-stimulated progesterone production was significantly correlated only with proteoglycan synthesis and not with GAG production. The addition of various concentrations of beta-D-xyloside (0.1-4 mM) for 48 h to granulosa cells induced a dose-dependent inhibition of FSH-stimulated progesterone secretion and [3H]thymidine incorporation into DNA. beta-D-Xyloside concentrations lower than 1 mM induced an inhibition of FSH-stimulated progesterone secretion but had no significant effect on FSH-induced proliferation. One millimolar beta-D-xyloside did not modify basal progesterone production, but in the presence of various doses (0.1-2.5 ng/ml) of FSH or hCG (0.1-1 IU/ml) it exerted a significant inhibitory effect on steroid secretion. Fifty percent inhibition was obtained for doses of FSH above 0.5 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780017 TI - Luteotrophic and luteolytic interactions between bovine small and large luteal like cells and endothelial cells. AB - Endothelial cells, the most abundant cell type in the bovine CL, were shown to establish intercellular contact with steroidogenic cells of the CL. Two experimental models were used to study the involvement of endothelial cells in luteal cell function: 1) luteal slices in which the integrity and communication between the different cells were maintained and 2) pure large and small luteal like cells, cultured separately or co-cultured with endothelial cells. The luteolytic effect of prostaglandin (PG) F2 alpha was examined in these two models. Treatment with PGF2 alpha did not alter P4 secretion stimulated by LH in young (2-4-day-old) CL slices, whereas, in slices from mature (6-12 days old) CL, PGF2 alpha significantly reduced (by 40%) the stimulatory effect of LH on P4 secretion. In pure large luteal-like cells, the effect of forskolin plus PGF2 alpha on P4 secretion did not differ from forskolin given alone after 3 or 24 h of incubation. However, when co-cultured with endothelial cells, PGF2 alpha significantly inhibited forskolin stimulation. Endothelial cells significantly stimulated P4 production from large luteal-like cells only. This effect may be attributed to the action of PGI2 secreted by endothelial cells. In summary, endothelial cells may play an essential role in luteal functions by being involved in both luteotrophic and luteolytic processes. PMID- 7780018 TI - Construction of an engineered bivalent vaccine strain consisting of Vibrio cholerae CT-B and LPS-O antigens. AB - In this study, the engineered E. coli strain 1046 containing V. cholerae LPS-O and CTB bivalent antigen genes has been successfully obtained by using DNA recombinant techniques. E. coli 1046 (pMG305) could not only express CT-B antigen but also secret CTB into medium as shown by GM1-ELISA. Meanwhile, whole cell O antigen-ELISA, bacterial agglutination test and hemagglutination inhibition assay demonstrated that LPS-O antigen could be expressed on the cell surface by E. coli 1046 (pMG305) and shown LPS band specific for V. cholerae by SDS-PAGE assay. Mouse intraperitoneal immunization and challenge trial indicated that the E. coli 1046 (pMG305) provided good protection against virulent V. cholerae. The engineered vaccine strain reported here is expected to be a live oral candidate vaccine for V. cholerae. PMID- 7780019 TI - Construction and expression of high efficiency expressing plasmid of transforming growth factor alpha-Pseudomonas aeruginosa exotoxin fusion protein TGF alpha PE40. AB - The XbaI/EcoRI cleaved TGF alpha-PE40 gene from plasmid pXY382 was inserted into the same cloning site of the expression vector pCB604 resulting in the plasmid p2X-TP1. E. coli BL21 (lambda DE3) cells were transformed with the p2X-TP1 and then induced with IPTG. The product expressed was accumulated mainly in the form of inclusion bodies. The expression level was closely related to the cell density, induction temperature and medium but not to the inductor dosage and the induction period within certain range. The expressed amount of the fusion protein TGF alpha-PE40 was about 50 mg/L. PMID- 7780020 TI - Expression and secretion of alpha-amylase and glucoamylase in Saccharomyces cerevisiae. AB - alpha-Amylase genes of Bacillus licheniformis and glucoamylase cDNA of Aspergillus niger were ligated to a E. coli-yeast shuttle vector. The resultant plasmid was used to transform Saccharomyces cerevisiae to construct starch degrading yeast strain. The results of enzyme activity assay and enzyme property analysis show that alpha-amylase and glucoamylase genes have been expressed simultaneously in yeast under the control of promoters and terminators of yeast MF-alpha 1 factor and PGK genes and over 99% of enzyme activities were secreted to the medium. The engineered yeast strain hydrolyses 97% of the starch (10%) in the medium after 6 days. The recombinant plasmid exists stably in yeast. PMID- 7780021 TI - Expression and immunogenicity of tripeptide repeat region on P190 of Plasmodium falciparum. AB - A DNA fragment, designated as P190TR, encoding amino acid residues of the tripeptide region of the P190 antigen was amplified by polymerase chain reaction from genomic DNA of FCC1/HN Plasmodium falciparum isolated from Hainan Province, China. Upon comparison with the nucleotide sequences of MAD20 allele, it was found that there were five bases substitution in the P190TR which cause amino acid changes. The DNA fragment sequenced were ligated to BamHI and XbaI-digested pGEX-2T vector. Competent E. coli JM109 (DE3) were transformed with either parental or recombinant pGEX-2T for expression. Analysis of soluble cellular proteins revealed the high level expression of GST-P190TR as fusion proteins. Affinity purification of the fusion protein under nondenaturing condition resulted in the removal of almost all other E. coli proteins. The purified P190TR protein was highly immunogenic in rabbits. The antibodies against the recombinant protein recognized the malaria parasite with the titers at 1:320 measured by IFA and antisera from malarial patients reacted with the expressed protein in Western Blot. PMID- 7780022 TI - Human alpha atrial natriuretic peptide fermentation by using a genetically engineered yeast strain. AB - The genotype of the recombinant yeast strain Y33::YFD71-3 used in this study is alpha, his, leu, ade and suc. Preliminary batch cultures in shaking flasks showed the expression level of atrial natriuretic peptide (ANP) was 1-2 mg/L. Shaking flask cultures were carried out in YG medium which contained glucose, yeast nitrogen base (YNB), and different amounts of adenine, histidine and leucine. When the growth was limited by adenine, protein secreted from Y33::YFD71-3 cells was increased obviously. Adenine became the limiting substrate when the YG medium was supplemented with 5 g/L of casamino acid (CAA) and the level of ANP expression was influenced by the concentrations of adenine, YNB and leucine in the medium. In fed batch cultures carried out in a RIBE-5 fermenter, the cultures were fed with glucose and a mixture of YNB, CAA, adenine, histidine and leucine to improve cell growth and ANP expression, and the maximum ANP concentration in the culture reached 24.8 mg/L. PMID- 7780023 TI - Establishment of the microorganism growth model at an inhibitory condition by microcalorimetric method. AB - The growth thermograms of Staphylococcus albus and Staphylococcus aureus were determined by using the 2277 thermal activity monitor, using a microorganism growth model with inhibitory conditions, the specific growth rate and the thermogram curves at different temperature and acidities were determined. From these curves, the microorganism optimum growth temperature and acidity were defined. PMID- 7780024 TI - Pseudohomogeneous kinetic study on a two-liquid-phase fermentation process. AB - The fermentation process for producing undecane dicarboxylic acid from tridecane, which includes gas-oil-water-cell four phases (two-liquid-phase), was studied. The metabolic characters of the cell growth phase and the production phase of the process were analyzed. It was proposed that cell growth can be identified by the carbon dioxide production rate (CPR) before the production phase. The kinetic models of both the cell growth phase and the production phase were established, respectively. The parameters of the models have been estimated by regression. The calculated curves fit the experimental data very well. The average deviation between those over the cell growth phase and the production phase are 2.4% and 3.6%, respectively. PMID- 7780025 TI - Studies on the condition of fermentation of pullulan by Aureobasidium pullulans. AB - Studies on optimal conditions for pullulan fermentation based on the results obtained from a shaking flask were carried out in a 16-L auto-controlling fermentor. It found that the optimal DE value of starch hydrolyzate was 40-50 when 10% starch hydrolysate was used as carbon source. The optimal concentration of ammonium sulfate in the medium for fermentation was different from that of the shaking flask. The fermentation kinetics and effects of seed age, seed volume, airflow rate, pressure of tank, agitation speed and number of vane group on the production of pullulan were investigated. PMID- 7780026 TI - Determination of L-glutamate using flow injection analysis with immobilized L glutamate oxidase reactor. AB - L-Glutamate oxidase (GOD) and horseradish peroxidase (HRP) were covalently coupled on alkylamine pretreated controlled pore glass (CPG) by means of glutaraldehyde. The immobilized enzymes were packed into a teflon tube and used in flow injection analysis (FIA) system for L-glutamate determination. A good linearity range was obtained at 0.1-2.0 mM, and the coefficient of variation was 0.7% (n = 8). More than 80 samples were measured within an hour. The stability of the immobilized GOD reactor was good, retaining 50% of its initial activity after 4 months storage in buffer at 4 degrees C. When the concentration of L-glutamate remained lower than 2.5 mM, the determination of L-glutamate in this system was not affected by pH and temperature within the range of 6.0-8.0 and 20-35 degrees C, respectively. The system was applied to determine L-glutamate in broth samples during L-glutamate fermentation and good correlations were achieved between results obtained with the FIA system, L-glutamate oxidase kit and Warburg's method. PMID- 7780027 TI - Exploring the peptide 3(10)-helix reversible alpha-helix equilibrium with double label electron spin resonance. AB - Over the last several years we have used spin labeling as a means for exploring the structure of helical peptides. Two nitroxide labels are engineered into a peptide sequence and distances are ranked with electron spin resonance (ESR). We have found that there is a significant amount of 3(10)-helix in 16-residue model peptides containing only L-amino acids. This review covers several facets of the methodology including spin labeling strategy, interpretation of ESR spectra and the influence of molecular dynamics on the spectral line shapes. Also covered are recent findings of a length-dependent 3(10)-helix-->alpha-helix transition and the role of Arg+ in the stabilization of specific helix structures. PMID- 7780028 TI - Vibrational optical activity of oligopeptides. AB - Vibrational optical activity (VOA) is a relatively new spectroscopic technique, which has two principal manifestations, ir vibrational CD and vibrational Raman optical activity. Progress in the study of oligopeptides using both of these forms of VOA is reviewed from the perspective of theoretical and instrumental techniques, spectral results, and structural interpretations. PMID- 7780029 TI - Cloning, tissue expression and regulation of rat interleukin 1 beta converting enzyme. AB - Using oligomer primers based on the cDNA sequence of human interleukin 1 beta converting enzyme (ICE), we have employed the RT-PCR method and rat spleen RNA to clone and sequence rat ICE. We report here that the predicted amino acid sequence of rat ICE proenzyme consists of 402 amino acids (p45) and shares 61% and 90% identity, respectively, with human and mouse ICE amino acid sequences. The active site cysteine (Cys284) and 3 or 3 potential processing sites are conserved suggesting that their the rat ICE heterodimer consists of a p22 (Ser104-Asp296) and a p10 (Gly315-His402) subunit or a cryptic processing site creates a smaller heterodimer. Northern blot analysis has revealed a approximately 2.2 kb and a more abundant approximately 1.45 kb ICE transcript both widely expressed in the rat with the highest expression in spleen and intestine and lowest in brain. IL-1 beta mRNA was similarly distributed. Injection of the immunostimulant, lipopolysaccharide (0.2 mg/kg, i.p.), increased rICE mRNA content between 2- to 3 fold in the rat brain with smaller increases measured in testis and spleen. The structural conservation of this enzyme suggests that rat models of inflammation will be useful for evaluating the therapeutic potential of ICE inhibitors in humans. PMID- 7780030 TI - Human interleukin for DA cells/leukemia inhibitory factor and oncostatin M enhance membrane expression of intercellular adhesion molecule-1 on melanoma cells but not the shedding of its soluble form. AB - ICAM-1-mediated cell-cell adhesion is essential for different immunologic functions including non-MHC-restricted cytotoxicity. The shedding of a soluble form of ICAM-1 from melanoma impairs immune recognition and leads to tumour escape. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane ICAM-1 twofold without inducing sICAM-1 shedding. Conversely, TNF-alpha, in the same conditions, strongly stimulated membrane ICAM-1 expression and the shedding of the soluble form. The same phenomenon was observed on the A375 human melanoma cell line. ICAM-1 upregulation was concomitant with an increase in the non-MHC-restricted cytotoxicity of tumour cells mediated by LAK cell.s This higher sensitivity to LAK lysis was abolished by RR1/1, a specific monoclonal antibody against ICAM-1. Our results demonstrate for the first time the ability of HILDA/LIF and OSM to upregulate ICAM-1 expression on the melanoma cell surface, suggesting a potential role for these cytokines in human immune surveillance during tumour progression. PMID- 7780031 TI - Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. AB - When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL 6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches. PMID- 7780032 TI - Leukaemia inhibitory factor (LIF) suppresses proteoglycan synthesis in porcine and caprine cartilage explants. AB - Leukaemia Inhibitory Factor (LIF) has been implicated in connective tissue damage in arthritis. We have previously shown that LIF stimulates proteoglycan release in pig cartilage explants. The aim of this study was to determine whether LIF modulates proteoglycan synthesis in vitro. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagles medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative control) or LIF. During the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose-dependent suppression of proteoglycan synthesis was observed with murine and human recombinant LIF in pig and goat cartilage. The degree of inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inhibitor of proteoglycan synthesis in cultured pig and goat articular cartilage. PMID- 7780033 TI - Soluble interleukin 6 receptor is biologically active in vivo. AB - A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 x C3H or SCID mice. Whereas B 78 cells formed tumours and lung metastasis in injected animals, transfected animals, transfected cells showed greatly reduced tumour and metastasis formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects. The combination of IL-6 and sIL-6R was most effective. Kinetic analysis demonstrated a 3 week lag period between formation of tumours by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-IL-6 or B-78-sIL-6R were injected alone. These results indicate that IL-6 alone exhibits a different quality of activity when compared to the IL-6-soluble receptor complex. Our results demonstrate for the first time that sIL-6R is a biologically active molecule in vivo. PMID- 7780034 TI - Ciliary neurotrophic factor (CNTF) induces serum amyloid A, hypoglycaemia and anorexia, and potentiates IL-1 induced corticosterone and IL-6 production in mice. AB - Ciliary neurotrophic factor (CNTF) supports the survival of ciliary ganglion neurons and was shown to induce the synthesis of acute-phase proteins and fever. We studied the effect of CNTF, alone or in association with IL-1, on levels of corticosterone (CS), glucose, serum amyloid A (SAA), and IL-6. We also compared the effect of CNTF with that of IL-6, since the gp130 receptor subunit for CNTF is shared with that of IL-6. A single intravenous injection of CNTF induced hypoglycaemia and SAA and potentiated IL-1-induced CS and IL-6. Chronic CNTF, but not IL-6, resulted in decreased food intake and body weight up to days 6-7. After this time, body weight and food intake recovered even if CNTF treatment was continued, indicating that a phenomenon of tolerance occurred. Finally, CNTF (unlike IL-1) was not toxic in adrenalectomized mice. Therefore the similarities of CNTF activities with those of other cytokines, particularly IL-6, might go beyond the activation of the same receptor-signal transduction pathway of IL-6. PMID- 7780035 TI - The role for host-immune factors in the in vivo antiviral effects of tumour necrosis factor. AB - This report examines the host-immune response to vaccinia virus in mice exposed to tumour necrosis factor (TNF). Exposure to TNF was done via two approaches; (1) mice were treated with TNF in complex with a specific anti-TNF antibody (Ab 301) which enhances the antiviral efficacy of this cytokine, prior to vaccinia virus (VV) infection; and (2) mice were infected with a recombinant VV which encodes the murine TNF gene (VV-HA-TNF). The antiviral effect induced by TNF plus Ab 301 in CBA/H mice was not sensitive to sub-lethal gamma irradiation, indicating that a proliferative immune cell population was not responsible for the observed attenuated VV growth. This was further evidenced by NK cell and CTL studies which showed, when compared to controls, that TNF plus Ab 301 treated animals had decreased spleen NK cell and CTL activities. This suggests that a non-specific factor, effective earlier than day 2 postinfection, was responsible for the restriction of VV growth. To further investigate this possibility, mice were treated with either the TNF/Ab 301 regimen, or infected with VV-HA-TNF, and their peritoneal exudate cells (PEC) examined during early VV infection. Control recombinant VV infection resulted in an increase in neutrophil numbers, and TNF/Ab 301 treatment before infection did not increase this further. VV-HA-TNF infection of mice, however, induced a massive but transient increase in the number of neutrophils, suggesting that this cell population was important to the in vivo restriction of VV-HA-TNF growth. PMID- 7780036 TI - In vitro cytokine production and T-cell proliferation in patients undergoing cardiopulmonary by-pass. AB - Cardiac surgery, employing cardiopulmonary by-pass (CPB), has long been associated with a generalized immunosuppression. To further understand the complex physiological and immunological changes related to CPB, we decided to investigate whether CPB affects the immune response, with regard to T-cell activation and cytokine production. Using phytohaemagglutinin (PHA) as mitogen and peripheral blood mononuclear cells (PBMC) isolated from patients undergoing CPB, we investigated whether this procedure has any effect on interferon gamma(IFN-gamma) and other cytokine production and/or PBMC proliferation. Comparisons were made between the responsiveness of PBMC obtained before, during and at the end of CPB. In all patients, CPB significantly reduces IFN-gamma and interleukin 2 (IL-2) production in response to PHA. On the other hand, tumour necrosis factor-alpha (TNF-alpha) production was also significantly diminished, while interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta) and interleukin 8 (IL 8) release in response to PHA was not significantly affected. Reduced IFN-gamma, IL-2 and TNF-alpha production was associated with a significant decrease in PBMC proliferation. These results might be related to the mechanical damage on blood cells described during extracorporeal circulation procedures as well as the release of immunosuppressive factors during surgery. The immunosuppression observed during CPB may play an important role in the development of infectious complications after CPB. PMID- 7780037 TI - Interleukin 4, but not interleukin 10, regulates the production of inflammation mediators by rheumatoid synoviocytes. AB - Rheumatoid synovitis is characterized by increased activation and proliferation of synoviocytes, which are an important source of cytokines. The role of Interleukin 4 (IL-4) and IL-10 on the production of mediators of inflammation by rheumatoid synoviocytes was studied herein. While IL-4 weakly affected the spontaneous PGE2 production, it strongly inhibited its production when cells were stimulated with IL-1 beta and TNF-alpha. IL-4 decreased by 60% to 80% the spontaneous and the IL-1 beta or TNF-alpha induced synthesis of GM-CSF. In contrast, IL-4 enhanced the spontaneous (2.6-fold), and to a lower extent (1.3 1.8-fold), the cytokine stimulated production of IL-6. This induction was not due to a passive release of pre-synthesized IL-6, since IL-4 increased the level of IL-6 mRNA expression induced by IL-1 beta. The D50 was 5 U/ml of IL-4 for both the stimulation of IL-6 synthesis and the inhibition of GM-CSF production. Kinetic studies of the action of IL-4 revealed a rapid and sustained inhibition of GM-CSF production, and a late increase of IL-6 secretion. By contrast, IL-10 had no effect on the production of either IL-6 or GM-CSF by synoviocytes. Thus, by inhibiting synoviocyte proliferation and inhibiting their secretion of PGE2 and GM-CSF, IL-4 displays on synoviocytes a series of biological effects which complements its anti-inflammatory properties on monocytes. PMID- 7780038 TI - Immunolocalization of TGF-beta 1 in human hypertrophic scar and normal dermal tissues. AB - Following severe thermal injury and other injuries to the deep dermis of the skin, patients frequently develop hypertrophic scarring (HSc) which is characterized by an over-abundance of extracellular matrix (ECM) proteins including collagen. Our previous work revealed a synchronous elevation in expression of mRNA for transforming growth factor (TGF)-beta 1, type I and type III procollagen in human HSc tissue, suggesting a possible role of locally synthesized TGF-beta 1 in matrix production. In this study the immunoreactive sites of TGF-beta 1 protein in hypertrophic and normal dermal (ND) tissue obtained from the same patients have been determined by an immunoperoxidase staining system. We used two TGF-beta 1-specific rabbit polyclonal antibodies known as anti-LC and anti-CC which were prepared to different synthetic preparations of a peptide corresponding to the first 1-30 amino acids of the amino-terminus of mature TGF-beta 1. These antibodies have affinity for two distinct epitopes of TGF-beta 1. The anti-LC antibody localized TGF-beta 1 to non proliferating/differentiated epidermal cells, suprabasal keratinocytes in both normal and HSc tissues. The intensity of this staining was significantly higher (150 +/- 26 sq. micron vs 77 +/- 7 sq. micron, n = 5, P < 0.05) in normal tissues compared to HSc tissues. When the anti-CC antibody was used as the primary antibody, intense staining of focal regions was observed in the dermis of HSc tissue, but not in ND tissue obtained from the same patient. These foci contained collagen which was nodular, distributed in whorl-like arrangements and highly enriched with microvessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780039 TI - Serum interleukin 6 as a predicator of the therapeutic effect and adverse reactions after transcatheter arterial embolization. AB - To evaluate the value of serum interleukin 6 (sIL-6) for the prediction of therapeutic effect and adverse reaction after transcatheter arterial embolization (TAE), sIL-6 was measured before and after angiography or TAE in 18 patients (three after angiography and 15 after TAE for hepatocellular carcinoma). The three patients with only angiography showed no elevation of sIL-6, while a significant increase was observed after TAE in the 15 hepatocellular carcinoma patients. The sIL-6 levels of patients with a partial response to TAE were higher at 48-72 hours after the procedure than those of patients with no response (P = 0.045), and the sIL-6 levels of patients who showed adverse reactions were higher at 6-24 h than those of patients without adverse reactions (P = 0.019). sIL-6 level at 48-72 h after TAE reflects the efficacy of TAE, whereas the level at 6 24 h after TAE is related to the severity of adverse reactions. Therefore, sIL-6 may be a useful indicator for prediction of the therapeutic effect of TAE as well as adverse reactions. PMID- 7780040 TI - Inhibition of cytokine activation processes in vitro by tenidap, a novel anti inflammatory agent. AB - Tenidap is a novel anti-inflammatory and anti-arthritic agent that lowers intracellular pH and suppresses anion transport when applied to cells in vitro. Both of these parameters are known to influence pro-inflammatory cell function. To investigate whether tenidap can modulate cellular responses to cytokine stimulation, several in vitro cytokine-driven assays were characterized with respect to their tenidap sensitivity. Human monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) demonstrated an increased production of IL-6 as well as an increased total translational activity. Tenidap dose-dependently inhibited both cytokine-induced responses; the effect on IL-6, however, occurred at lower tenidap concentrations than those required to prevent the increase in total translational activity. In contrast, the known translational inhibitor cycloheximide did not demonstrate selectivity for IL-6; this agent decreased the GM-CSF-induced increase in total translational activity in parallel with its effects on IL-6. GM-CSF-treated monocytes also produced greater amounts of IL-1 beta in response to LPS stimulation than did non-GM-CSF treated cells, and tenidap again suppressed this cytokine-induced activation. Human Hep3B cells treated with a combination of interleukin (IL)-1 beta and IL-6 demonstrated an acute phase-type of response. These hepatoma cells increased production of the positive acute phase protein serum amyloid A (SAA) while they decreased production of a negative acute phase protein human serum albumin (HSA). Tenidap dose-dependently inhibited the cytokine-induced increase in SAA production without effecting synthesis of HSA or total TCA-precipitable macromolecules. Importantly, the ability of tenidap to alter these various cytokine responses was not shared with piroxicam, a potent cyclooxygenase inhibitor. Finally, human neutrophils treated with either GM-CSF or tumor necrosis factor (TNF)-alpha demonstrated an increased chloride conductance as measured by the loss of radioactive chloride from 36Cl-loaded cells. When tenidap was included within the medium during cytokine stimulation, loss of radioactive chloride was prevented. Thus, tenidap inhibited the cytokine-induced increase in anion transport. Together, these results indicate that tenidap can suppress cellular activation processes induced by a variety of cytokines. This functional antagonism is not dependent on cyclooxygenase inhibition but, rather, appears to link to tenidap's unique ability to alter ionic homeostasis. These in vitro observations, therefore, may help to explain how this novel anti-inflammatory agent acts to lower acute phase proteins and IL-6 levels in man. PMID- 7780041 TI - Synovial fluid from rheumatoid arthritis patients contains sufficient levels of IL-1 beta and IL-6 to promote production of serum amyloid A by Hep3B cells. AB - The presence of positive acute phase proteins within the circulation of rheumatoid arthritis patients suggests that elevated cytokine production associated with this chronic inflammatory disorder initiates the hepatic acute phase response. Cytokines produced at inflammatory lesions are believed to travel via the circulation to the liver where they induce acute phase protein production by hepatocytes. To test whether serum from rheumatoid arthritis patients contained sufficient levels of cytokines to promote an acute phase response in vitro, a bioassay was developed that employed the human hepatoma cell line Hep3B. These cells produced the acute phase protein serum amyloid A (SAA) in response to a combination of recombinant IL-1 beta and IL-6 or to monocyte conditioned medium. Serum (or plasma) from normal individuals or from rheumatoid arthritis patients did not induce SAA production by Hep3B cells. Moreover, these serum samples did not prevent SAA production induced by monocyte conditioned medium, indicating that they did not contain inhibitors of cytokine activity. Despite the inactivity of serum samples, synovial fluid samples obtained from rheumatoid arthritis patients were active in the hepatocyte bioassay and promoted SAA synthesis. One synovial fluid sample was analysed in detail to identify cytokines responsible for the SAA-inducing activity. Neutralizing antisera against IL-6 and IL-1 beta blocked this activity by > 90% whereas anti-IL1 alpha and anti-TNF alpha sera were without effect. Absolute cytokine levels within the synovial fluid sample were determined by ELISA; IL-6, IL-beta and TNF-alpha, but not IL-1 alpha, were confirmed to be present. Moreover, the synovial fluid sample contained a large amount of the IL-1 receptor antagonist. These data indicate, therefore, that synovial fluid recovered from an inflamed joint contains all the necessary cytokines in balance with inhibitors to promote SAA production by Hep3B cells. The steady state levels of these factors within the plasma compartment, however, were insufficient to induce the acute phase response by cultured Hep3B cells, suggesting that this system does not mimic the relationship between the circulation and the liver that likely exists in rheumatoid arthritis patients. PMID- 7780042 TI - Increased levels of serum macrophage colony stimulating factor (M-CSF or CSF-1) in patients with chronic renal insufficiency (CRF): facts and hypotheses. PMID- 7780043 TI - Chemical synthesis, purification and folding of the human monocyte chemotactic proteins MCP-2 and MCP-3 into biologically active chemokines. AB - Monocyte chemotactic proteins 2 and 3 (MCP-2 and MCP-3) are chemokines structurally and functionally related to MCP-1. In contrast to MCP-1, they are produced in low amounts by stimulated leukocytes or tumour cells. As an alternative method to generate sufficient protein for in vitro and in vivo characterization of MCP-2 and MCP-3, we have synthesized both 76-residue chemokines using Fmoc chemistry. After automated solid phase peptide synthesis at a 0.05 to 0.25 mmol scale, and purification to homogeneity by C-8 RP-HPLC, correct disulfide bridges were formed in a mixture of oxidized and reduced glutathione. The synthesis was biochemically controlled by peptide sequencing of intermediate products and proteolytic fragments of the 76-residue chemokines and by mass analysis. Purified synthetic MCP-2 and MCP-3 coeluted and comigrated with their natural counterparts on analytical reverse phase columns and SDS-PAGE, respectively. Purified and folded MCP-2 and MCP-3 were chemotactic for monocytes at 7.5 ng/ml and 5 ng/ml, respectively. These minimal effective concentrations are comparable to those of the natural chemokines. Synthetic MCPs did not induce neutrophil chemotaxis. Automated Fmoc peptide synthesis is thus a useful method, allowing fast production of chemokines and analogues thereof. PMID- 7780044 TI - Pharmacokinetics of the novel anticonvulsant HEPP after single intravenous administration of three different doses in dogs. AB - HEPP (D, L-3-hydroxy-3-ethyl-3-phenylpropanamide) is a novel compound with a wide spectrum of anticonvulsant activity and relatively low toxicity. The aim of this investigation was to study the pharmacokinetics of HEPP in mongrel dogs and to assess its linearity after intravenous administration of 8, 15, and 30 mg kg-1. A biphasic disappearance pattern with a rapid distribution phase was observed in the plasma concentration versus time curve. The mean terminal half-life (t1/2 beta) was the same after the three doses (3.4 +/- 0.15 h) and the mean half-lives of the distribution phase (t1/2 alpha) were not significantly different after the three doses (0.09 +/- 0.02, 0.08 +/- 0.07, and 0.11 +/- 0.03 h for 8, 15, and 30 mg kg-1 respectively). The mean AUC0-infinity values were 44.1 +/- 10.8, 72.1 +/- 8.8, and 127.4 +/- 23.2 micrograms h mL-1, respectively, showing a linear increase. The individual values of AUC0-infinity corrected for the administered dose (AUC0-infinity/D) were 0.29 +/- 0.04, 0.23 +/- 0.05, and 0.22 +/- 0.06 h mL 1. These values were not statistically different. Neither the mean residence time (MRT = 4.55 +/- 1.50, 4.90 +/- 1.32, and 5.07 +/- 1.95 h), the steady state volume of distribution (Vss = 0.86 +/- 0.11, 1.01 +/- 0.17, and 1.20 +/- 0.40 L kg-1) nor the systemic clearance (Cl = 3.36 +/- 0.82, 3.53 +/- 0.44, and 4.02 +/- 0.68 mL min-1 kg-1) showed significant differences between doses. The values of Vss suggest that HEPP is distributed in the whole body fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780045 TI - Kinetic modelling of liposome degradation in peritoneal macrophages. AB - The objective of this study was to quantify and model the degradation process of liposomes in peritoneal macrophages (PMs). Iodinated albumin (125I-alb) was chosen to be the marker of liposome degradation. The time course of the degradation of free 125I-alb after pinocytosis by PMs followed first-order kinetics with a half-life of 23 min. The degradation of liposomally encapsulated 125I-alb was also quantified. Kinetic modelling of liposome degradation indicated the existence of two kinetically different processes, one with a half-life of 13 min and the other with a half-life of 7.5 h. Comparing the degradation of liposomal and free 125I-alb suggested that 125I-alb was delivered to lysosomes much faster through phagocytosis than pinocytosis. These results indicate that the intracellular degradation kinetics of pinosomes and phagosomes is different. This method can quantify the rate and extent of liposomal degradation in macrophages and provide kinetic information on the intracellular destiny of liposomally encapsulated compounds. PMID- 7780046 TI - Dose proportionality of stavudine in HIV seropositive asymptomatic subjects: application to bioequivalence assessment of various capsule formulations. AB - The dose proportionality and bioequivalence of the capsule formulations used in clinical trials and the proposed commercial formulations of stavudine were assessed in an open-label, single-dose, randomized four-way crossover study in 16 asymptomatic HIV-infected males. One capsule of stavudine (5, 10, 20, or 40 mg) was administered orally to each subject in each of the four treatment periods. Serial blood samples were collected for 10 h after each dose and the plasma was assayed for intact stavudine by a validated radioimmunoassay method. The plasma concentration-time data were subjected to non-compartmental pharmacokinetic analysis. For doses ranging from 5 to 40 mg, mean Cmax and AUC0-infinity values were in the range of 110.36-889.34 ng mL-1 and 246.46-1945.97 h ng mL-1 respectively. The mean Cmax and AUC0-infinity of stavudine increased in a dose proportional manner. Irrespective of the dose, mean Cmax values were observed at a median tmax of 0.75 h or less. Mean t1/2 values were 1.97, 1.77, 1.67 and 1.66 h for the 5, 10, 20, and 40 mg capsules, respectively. For bioequivalence assessment, Cmax and AUC0-infinity values were normalized to the 10 mg dose since these parameters were dose proportional. The 10 mg capsule formulation used in phase-3 clinical trials was chosen as the reference. The relative bioavailability estimates and 90% confidence limits for the dose-normalized Cmax values with the 10 mg capsule as the reference were 86% (76%, 96%), 99% (88%, 110%), and 90% (80%, 100%) for the 5, 20, and 40 mg capsules, respectively. The differences in the point estimates of the dose-normalized AUC0-infinity values for the 5, 20, and 40 mg capsules relative to the 10 mg phase-3 capsule were 1% or less, and the 90% confidence limits were all within 95-106%. These results indicate that stavudine exhibits linear pharmacokinetics and that the 5, 10, 20, and 40 mg capsules of stavudine are bioequivalent. PMID- 7780047 TI - The effect of the fat content of food on the pharmacokinetics and pharmacodynamics of SDZ FOX 988, an antidiabetic agent, in the dog. AB - SDZ FOX 988 (FOX 988) is being developed for the treatment of type II diabetes. The objective of this study was to examine the effect of the fat content of food on the pharmacokinetics and pharmacodynamics of FOX 988 following oral administration in the dog. In a randomized, cross-over design, four dogs received a single 10 mg kg-1 dose of 14C-FOX 988 suspension concomitantly with food containing 10% fat or 40% fat, or with the 10% fat food at 4 h post-dose. Serial blood, urine, and fecal samples were collected for 96 h and analyzed for total radioactivity. Blood concentrations of 53-450, the active metabolite of FOX 988, were also determined. Serum concentrations of beta-hydroxybutyrate and glucose, pharmacological markers for the antidiabetic effects, were measured serially for 24 h after dosing. The animals receiving the low-fat meal at dosing and at 4 h post-dose exhibited similar extents of absorption, as shown by similar AUC values and urinary radioactivity recovery. Administration of the high-fat meal at dosing significantly enhanced the absorption of FOX 988 and resulted in high blood concentrations of 53-450. However, no significant differences in the pharmacological activity of the drug were observed among the three treatments. PMID- 7780048 TI - Uptake and biodisposition of 2-ylcyanamide-1,3,4-thiadiazole (LY217896) by red blood cells. AB - In man, 14C-2-ylcyanamide-1 3 4-thiadiazole (LY217896) accumulates into red blood cells (RBCs) where it is rapidly metabolized. Both in man and ex vivo, within a few hours of administration of 14C-LY217896 at least two intracellular metabolites were detected within the RBCs using HPLC. These metabolites were never detected extracellularly. After 24 h no detectable radioactivity was found in the plasma and all the radioactivity was detected within the cellular fraction. All radioactivity was identified as a single peak within the RBCs, indicating the metabolite(s) to be highly polar compared to LY217896. Parent LY217896 was never detected within the RBCs at any time point, suggesting transport, either by diffusion or a carrier mediated mechanism, was the rate limiting step. Due to the nature of the preparation it was impossible to separately characterize uptake and biotransformation. Nevertheless, uptake/biotransformation was found to be temperature sensitive, sodium independent, and energy dependent. Both niacin and vitamin B6, but not nicotinamide, competitively blocked the uptake and subsequent intracellular metabolism of LY217896. PMID- 7780049 TI - Disposition kinetics of HEPP in rats after intravenous, oral, and intraperitoneal administration. Correlation of plasma and brain levels with the anticonvulsant effect. AB - D, L-3-hydroxy-3-ethyl-3-phenylpropanamide (HEPP) is a synthetic drug with anticonvulsant effects in a variety of seizure models. HEPP pharmacokinetics was studied after single 50 mg kg-1 intravenous (i.v.), intraperitoneal (i.p.), and oral (PO) administration in male albino Wistar rats. The plasma concentration against time curves showed a biphasic decay pattern with a similar distribution phase and the same terminal rate constant (beta = 0.22 h-1) by all three routes. The apparent volume of distribution at steady state (Vss = 0.80 L kg-1) indicates that HEPP is extensively distributed in extracellular tissues. This finding agrees very well with its low binding to plasma protein (mean bound fraction = 19.3 +/- 1.1%). The systemic clearance (Cl) was very low (3.30 mL min-1 kg-1). The bioavailability after IP and PO administration was 0.80 and 0.60 respectively. In the pharmacokinetic-pharmacodynamic studies a direct relationship was found between the protective effect of HEPP against pentylenetetrazole (PTZ) induced seizures and its concentration in plasma and/or brain. The concentrations at half-maximal effect (EC50) with 95% confidence interval (Cl) were 70.6 (66-75.5) micrograms mL-1 in serum and 60.1 (55.4-65.1) micrograms g-1 in brain. There was a rapid uptake of HEPP into the brain, and after the distributive phase, the disappearances in plasma and brain were almost parallel [C(serum) = 109 e-0.25t, r2 = 0.95; C(brain) = 38 e-2.53t + 91 e-0.21t, r2 = 0.93], with a C(brain)/C(plasma) ratio of 1.1. PMID- 7780050 TI - Plasma lipoproteins as targeting carriers to tumour tissues after administration of a lipophilic agent to mice. AB - We synthesized 14C-warfarin hexadecyl ether (14C-WHE) by addition of a palmityl moiety to the hydroxyl group at the 4-position of 14C-warfarin, a compound known to bind to serum albumin. 14C-WHE preferentially bound to the lipoproteins, low density lipoprotein (LDL) and high-density lipoprotein (HDL), in mouse plasma both in vitro and in vivo. 14C-Warfarin mainly concentrated in the liver immediately after intravenous administration to mice bearing M5076 sarcoma, and was found at only low concentrations in other tissues including the tumour. 14C WHE highly distributed to the tumour, adrenal, and spleen, as well as the liver. These tissues coincided with those in which human 125I-LDL was vigorously incorporated. The results indicate that chemical modification of an agent, giving it high lipophilicity, will enable it to bind to lipoproteins after intravenous administration. These modifications raise the possibility of lipoproteins as endogenous targeting carriers into tumour cells, which have high LDL-receptor activity. PMID- 7780051 TI - The thymic way to transplantation tolerance. AB - Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. The major goal in transplantation research remains the development of strategies that would allow one to achieve a state of donor specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals. The thymus plays the major role in the development of self-tolerance, and initial work in the late 1960s indicated that the thymus also plays a critical role in the induction of acquired tolerance to exogenous antigens. Recently, the interest in acquired thymic tolerance has been renewed by the observation that, in the rat, the thymus is an immunologically privileged site in which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection of the islets induced donor-specific unresponsiveness, which allowed survival of a second donor strain islet cell allograft transplanted into an extrathymic site. These findings on cellular allografts have been extended to vascularized organ allografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780052 TI - Syndrome of flank pain and acute renal failure after binge drinking and nonsteroidal anti-inflammatory drug ingestion. AB - The binge drinking of alcohol combined with the ingestion of a nonsteroidal anti inflammatory drug (NSAID) is a recently described cause of reversible acute renal failure. The pathogenetic mechanisms leading to acute tubular necrosis in this setting include the initial compromise in renal perfusion due to alcohol-induced extracellular volume contraction and the superimposed renal hemodynamic alterations induced by the NSAID that interfere with the renal autoregulation. Although alcohol may also cause rhabdomyolysis leading to acute tubular necrosis, this is usually not apparent in these cases. Previously, only three such cases have been reported but the incidence is likely to be higher in view of the prevalence of alcohol and NSAID use. Herein is presented another patient in whom the features of flank pain and acute renal failure in association with binge drinking and NSAID ingestion constitute a characteristic syndrome. PMID- 7780053 TI - Renal amyloidosis in a drug abuser. AB - Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis. PMID- 7780054 TI - Structural-functional relationships in Alport syndrome. AB - Renal morphometric analysis was performed in 15 (13 male) Alport syndrome patients ages 4 to 26 years, along with 10 controls ages 3 to 26 years, to better understand the structural basis of renal dysfunction in Alport syndrome. The glomerular basement membrane (GBM) width class frequencies of controls were normally distributed; those of Alport syndrome patients were slightly skewed, especially toward thicker classes, although there was also an increase in the proportion of thinner classes. Mesangial volume fraction was not different between Alport syndrome patients (0.21 +/- 0.09) and controls (0.19 +/- 0.04). There was an inverse correlation between mesangial volume fraction and creatinine clearance in Alport syndrome patients (r = -0.72, P < 0.01); however, the creatinine clearances in Alport syndrome patients were far less than in insulin dependent diabetic patients with similar mesangial volume fraction. Similarly, there was no significant difference in the surface density of the peripheral GBM (in square micrometers per cubic micrometer) in Alport syndrome patients (0.12 +/ 0.04) versus controls (0.13 +/- 0.02). The surface density of the peripheral GBM correlated with creatinine clearance in Alport syndrome patients (r = 0.71, P < 0.01). However, there was a greater reduction in creatinine clearance as related to declining the surface density of the peripheral GBM in Alport syndrome than in diabetic patients. The cortical interstitial volume fraction was highly inversely correlated with creatinine clearance in Alport syndrome patients (r = -0.85, P < 0.01). Global glomerular sclerosis was 0% in five and 5 to 61% in nine Alport syndrome patients and correlated inversely with creatinine clearance (r = -0.74, P < 0.01). However, the creatinine clearance was lower in Alport syndrome than in diabetic patients with similar cortical interstitial volume fraction and percent glomerular sclerosis. There was no significant difference in an index of glomerular number between Alport syndrome patients and controls. Thus, changes in mesangial volume fraction, cortical interstitial volume fraction, percent glomerular sclerosis, and surface density of the peripheral GBM in Alport syndrome patients only partially account for the reduction in creatinine clearance. It was speculated that decreased glomerular capillary wall hydraulic conductivity in Alport syndrome could explain many of these observations. PMID- 7780055 TI - Genesis of renal cysts is associated with clusterin expression in experimental cystic disease. AB - Phenol II is a cystogenic chemical that rapidly induces renal cysts, which regress after drug withdrawal. Cyst formation in this model parallels changes in the tubular basement membrane. Clusterin is a potent cohesive factor induced in states of tissue remodeling. The purpose of this study was to determine if renal clusterin was increased in the Phenol II model and to define the time course and distribution of its induction. Male Sprague-Dawley rats were given, by daily gavage, Phenol II (1.2 mg/kg per day) or vehicle (control). The kidneys were harvested after 1, 2, or 4 days of Phenol II treatment or 3 or 7 days after drug withdrawal. An increase in immunoreactive clusterin was seen in the kidneys of Phenol II-treated rats but not in controls. The appearance of clusterin followed a time course similar to that for cyst formation, with expression confined to the epithelial lining and intratubular casts of dilated or cystic tubules. After Phenol II withdrawal, renal cysts regressed and clusterin staining disappeared. The development of cysts was associated with an increase in clusterin mRNA that decreased after drug withdrawal. In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease. The function of clusterin in this setting remains enigmatic. PMID- 7780056 TI - Differential mRNA expression of renal cortical tissue inhibitor of metalloproteinase-1, -2, and -3 in experimental hydronephrosis. AB - The pathophysiologic sequelae of both acute and chronic experimental unilateral ureteral obstruction (UUO) in the rat are the result of a variety of complex humoral and cellular interactions. The development of interstitial fibrosis is dependent on the tightly coupled regulation of synthesis and degradation of extracellular matrix proteins. This laboratory, among others, has shown an up regulated expression of renal cortical transforming growth factor (TGF)-beta 1 within hours of the onset of UUO. Because a potential contribution of TGF-beta to fibrosis may be its ability to increase the expression of proteinase inhibitors such as members of the tissue inhibitor of metalloproteinase (TIMP) family, this laboratory now sought to delineate the kinetics of TIMP-1, TIMP-2, and TIMP-3 mRNA expression in the renal cortex after UUO. There was a marked elevation of TIMP-1 mRNA expression after UUO, which was first noted at 12 h after ureteral ligation. By 96 h after UUO; there was a 30-fold increment in TIMP-1 mRNA in the obstructed kidneys compared with the contralateral unobstructed kidney or sham operated rat specimens. In contradistinction to TIMP-1, a decrease in TIMP-3 mRNA levels was noted at 12 h after ureteral obstruction and persisted at the 24-, 48 , and 96-h time intervals. TIMP-2 gene expression remained at a relatively constant level during the entire study. It is proposed that the increased expression of TGF-beta 1 post-UUO induces a profibrogenic state and initiates a cascade of dysregulatory events including the up-regulation of TIMP-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780057 TI - Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects: a double-blind, placebo-controlled, multicenter trial. AB - Prostaglandins of the E series (PGE) are known to contribute to the maintenance of renal hemodynamics in subjects with chronic renal insufficiency. Agents that block PGE synthesis, nonsteroidal anti-inflammatory agents (NSAID), are widely used by people with renal insufficiency. This study was undertaken in subjects with renal insufficiency secondary to diabetes to evaluate the acute effects of a PGE1 analog, misoprostol, on NSAID-induced changes in RBF, as calculated by para aminohippurate clearance, and GFR, as calculated by inulin clearance. Sodium excretion was also assessed. Twenty-five fasting subjects with a mean age of 56 +/- 4 yr received 800 mg of ibuprofen orally. A concomitant dose of either a placebo (PL) or 200 micrograms of misoprostol was also given. This was followed in 1 h by either a placebo or an additional 200-micrograms dose of misoprostol. Measurements for the determination of RBF, GFR, blood pressure, and fractional excretion of sodium were performed every 30 min for the next 5 h. The greatest reduction in both GFR (-25 +/- 7 mL/min per 1.73 m2 PL versus -10 +/- 4 mL/min per 1.73 m2, misoprostol delta GFR; P < 0.05) and RBF (-48 +/- 21 mL/min per 1.73 m2 PL versus -15 +/- 8 mL/min per 1.73 m2, M delta RBF; P < 0.05) occurred approximately 2 h after the NSAID dose. No significant differences were noted in blood pressure, fractional excretion of sodium, or other measured parameters between groups during the entire study. Gastrointestinal upset was the most common side effect observed in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780058 TI - Impaired cation transport in thymocytes of rats with chronic uremia includes the Na+/H+ antiporter. AB - To examine how uremia changes sodium, potassium, and proton transport, thymocytes from chronic renal failure (CRF) rats were studied. If alterations in cation transport associated with chronic uremia (CRF) extend to intracellular pH regulation, the susceptibility to the catabolic effects of acidosis might be increased. To evaluate the influence of acidosis, cation transport in thymocytes from normal rats with NH4Cl-induced acidosis was also studied. Ouabain-sensitive 86Rb influx in thymocytes from acidotic CRF rats was 32% lower than in control cells (P < 0.05), but intracellular sodium concentration was unchanged. This may be related to a 47 +/- 22% reduction in 22Na influx. In thymocytes from nonuremic, acidotic rats, ouabain-sensitive 86Rb influx was decreased 39% (P < 0.025), similar to the change in CRF. In CRF thymocytes, Na(+)-H+ antiporter activity in response to cell acidification (7.13 +/- 0.8 versus 9.42 +/- 0.8 mmol of H+/L per min; CRF versus control), or to osmotic shrinkage (0.43 +/- 0.09 versus 0.82 +/- 0.11 mmol of H+/L per min; CRF versus control), was significantly (P < 0.01) reduced. Buffering capacity at resting and acidic intracellular pH was unchanged by uremia, but Na+/H+ antiporter activity in response to acid loading or osmotic shrinkage was unchanged in thymocytes of nonuremic rats with metabolic acidosis. Thus, CRF reduces both Na/K-ATPase and Na+/H+ antiporter activities in rat thymocytes. The former may be secondary to reduced sodium influx. Impaired Na+/H+ antiporter activity is not caused by metabolic acidosis alone, whereas reduced Na/K-ATPase activity is found in both acidosis and uremia. PMID- 7780059 TI - Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency. AB - Previous reports that polymorphonuclear leukocyte (PMN) function is impaired in hemodialysis patients do not differentiate between effects of dialysis and of uremia. The hypothesis that chronic renal insufficiency impairs PMN function was tested. Phagocytosis and oxidative burst were measured in PMN from patients with varying degrees of chronic renal insufficiency impairs PMN function was tested. Phagocytosis and oxidative burst were measured in PMN from patients with varying degrees of chronic renal insufficiency (creatinine clearance, 6 to 35 mL/min per 1.73 m2) and normal subjects. The ability of tumor necrosis factor-alpha (TNF alpha) to prime the oxidative burst was also assessed. Phagocytosis of Staphylococcus aureus and basal H2O2 and O2- release by PMN did not differ between normal subjects and patients with chronic renal insufficiency. However, the oxidative burst stimulated by S. aureus and formyl-Met-Leu-Phe, but not phorbol myristate acetate, was significantly enhanced in PMN from patients with chronic renal insufficiency. The increase in formyl-Met-Leu-Phe-stimulated oxidative burst correlated significantly with the level of renal function. TNF alpha significantly increased S. aureus-induced H2O2 production in normal PMN, but not in PMN from patients with chronic renal insufficiency. These data indicate that chronic renal insufficiency does not impair PMN phagocytosis and oxidative burst. To the contrary, it enhances receptor-mediated oxidative burst. The inability of TNF-alpha to further enhance the oxidative burst suggests that PMN exist in a primed state in patients with chronic renal insufficiency. PMID- 7780060 TI - High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients. AB - In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments. PMID- 7780061 TI - How should renal hemodynamic data be indexed in obesity? AB - Clearance data are customarily indexed to body surface area of 1.73 m2. This study examined whether this standard procedure gives correct values for renal perfusion in obese subjects. In 215 subjects who varied in age, gender, height, weight, obesity, and mean arterial blood pressure, RPF was determined by measuring the clearance of (131I)para-aminohippuric acid. Multiple regression analysis of the whole study group revealed that age (beta = -0.44, P < 0.001), height (beta = +0.25, P < 0.01), and arterial blood pressure (beta = -0.19, P < 0.01) were independent predictors of RPF, but that weight or body mass index was not. When related to body surface area, RPF appeared to decline with increasing obesity as follows: normal weight, 609 +/- 153 mL/min per 1.73 m2; overweight, 572 +/- 149 mL/min per 1.73 m2; severely overweight, 530 +/- 145 mL/min per 1.73 m2 (P < 0.012). In contrast, RPF related to height reflected a pattern concordant with the multiple regression analysis: normal weight, 3.76 +/- 0.9 mL/min per meter; overweight, 3.86 +/- 1.0 mL/min per meter; and severely overweight, 3.86 +/- 1.0 mL/min per meter (not significant). A separate repetition of the whole analysis for both normotensive (N = 55) and hypertensive subjects (N = 160) revealed a result similar to that found for the whole group. Thus, our results show that obesity was not a determinant of RPF, and when related to body surface area, inappropriately low values of RPF were calculated for obese patients. It was concluded that RPF values correlate with height and not with surface area in obese subjects. PMID- 7780062 TI - Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. AB - Autosomal recessive Alport syndrome can arise from a mutation in either of the genes COL4A3 and COL4A4 on chromosome 2, which encode, respectively, the alpha 3 and alpha 4 chains of Type IV collagen. This report describes a mutation in COL4A3 in a girl who presented at age 5 with hematuria and proteinuria, lacking any family history of renal disease. Renal biopsy at age 8 showed immunoglobulin A nephropathy and Alport syndrome. Sensorineural deafness developed during adolescence, and the patient's renal disease progressed to terminal renal failure by age 20. She received a living related donor renal allograft at age 20 and developed antiglomerular basement membrane nephritis of the allograft 8 months after transplantation. Amplification and sequencing of exon 5 of COL4A3 (counting from the 3' end of the gene) revealed a 7-base-pair deletion, producing a shift of the reading frame and the creation of a premature stop codon. Each parent was heterozygous for the normal and mutant exon 5 sequences. This mutation in COL4A3 would result in the loss of 222 amino acids from the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The mutant chain would be unable to form trimers with other Type IV collagen alpha chains. In addition, the mutant chain would lack the Goodpasture epitope, which resides in the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The absence of this epitope may underly the subsequent development of anti-glomerular basement membrane nephritis in the allograft. PMID- 7780063 TI - Endothelin A receptor mediates functional but not structural damage in chronic cyclosporine nephrotoxicity. AB - Chronic treatment with cyclosporine (CsA) is limited not only by glomerular hypofiltration but also by structural damage. The pathogenesis of these nephrotoxicities was studied in a model of chronic CsA-induced renal damage. Salt depleted rats were treated with daily CsA (15 mg/kg sc) for approximately 3 weeks, at which time renal function was measured and kidneys were harvested for morphologic assessment. A separate group of rats (CsA + BQ123) were identically treated with CsA but in addition also received simultaneous treatment with a specific endothelin A (EtA) receptor antagonist, BQ123, which was continuously delivered via sc osmotic pump (1 mg/kg per hour) and maintained throughout the study. Chronic CsA treatment caused profound functional and structural damage, although blood pressure was normal (102 +/- 6 mm Hg); GFR was 0.05 +/- 0.02 mL/min per 100 g body wt, and RPF was 0.15 +/- 0.06/100 g body wt. Renal injury was scored on a scale of 0 to 4 and showed dilation/vacuolization of 1.07 +/- 0.29 and tubulointerstitial fibrosis of 0.78 +/- 0.17. Arteriolopathy was present in 78 +/- 4% of arterioles. Chronic antagonism of the EtA receptor preserved renal function: GFR was 0.15 +/- 0.03 mL/min per 100 g body wt, and RPF was 0.32 +/- 0.08/100 g body wt (P < 0.05 for GFR versus CsA). Blood pressure was not affected: 104 +/- 8 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780064 TI - Choosing the appropriate double-lumen tube: a glimmer of science comes to a dark art. PMID- 7780065 TI - The relationship between left mainstem bronchial diameter and patient size. AB - Knowledge of a patient's left mainstem bronchial diameter would provide a useful guide to choosing the appropriate double-lumen tube (DLT) size for that patient. Therefore, the authors investigated the possibility that left bronchial diameter could be predictably estimated from a patient's size and sex. The routine preoperative chest X-rays of 100 adult male and female patients of known age, height, and weight were examined. The left bronchial diameter was measured on the posteroanterior (PA) chest x-ray, and a formula was used to correct for the magnification of intrathoracic structures encountered on the PA view. Multiple linear regression analysis was used to determine whether one or more of the variables (age, sex, height, weight, and body surface area) had a predictable relationship to the left bronchial diameter. The left mainstem bronchial diameter in men and women (mean +/- SD/range) was 12.4 +/- 1.5 mm/9.5 to 15.5 mm, and 10.7 +/- 1.0 mm/9.0 to 14.0 mm, respectively. In female patients, none of the variables was significantly correlated with bronchial diameter. In male patients, age (p = 0.013) and height (p = 0.008) individually produced a statistically significant prediction of endobronchial diameter. The following formula was best predictive of left bronchial diameter in men: diameter (mm) = 0.032 x age (year) + 0.072 x height (cm) -2.043. Applying this formula to mean age 50 who are 158, 172, and 185 cm in height, the predicted left bronchial diameters are 11.0, 12.0, and 13.0 mm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780066 TI - Incidence of malposition of polyvinylchloride and red rubber left-sided double lumen tubes and clinical sequelae. AB - Currently, fiberoptic bronchoscopy (FB) is recommended for correct positioning of double-lumen endobronchial tubes (DLTs) because of the high incidence of malpositions not appreciated by clinical signs. The aims of this study were to assess whether clinical signs allow accurate confirmation of adequate positioning with left red rubber (RR) or polyvinyl-chloride (PVC) double-lumen tubes and to compare the incidence of malpositions between the two tubes. Another goal was to assess whether these malpositions, not appreciated by clinical assessment, adversely affected outcome. Twenty-one adult patients scheduled for elective thoracic surgery were randomly assigned to the RR (11 patients) or PVC group (10 patients). After endobronchial intubation, the position of the tubes was adjusted until clinically satisfactory lung separation had been achieved. A single investigator performed all the FB assessments were performed in the supine (SUP) and lateral positions. The anesthesiologists responsible for the clinical evaluation were "blinded" to the bronchoscopic findings. While in the SUP position, the tube was "too deep" to permit visualization of the carina during tracheal bronchoscopy in 5 patients (2 RR, 3 PVC). In 17 of 21 (10 RR, 7 PVC), the bronchial cuff could not be visualized, although in 1 patient (RR group), the cuff was overinflated and bulged out to partially obstruct the right main bronchus orifice. Bronchial bronchoscopy showed 4 of 11 patients in the RR group in whom the left upper lobe orifice was occluded compared with 1 only in the PVC group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780067 TI - Postthoracotomy pulmonary function: a comparison of epidural versus intravenous meperidine infusions. AB - It has remained unclear whether epidural opioid analgesia permits better recovery of postthoracotomy pulmonary function than an optimal method of systemic opioid administration. Lumbar epidural meperidine infusions were compared with intravenous patient-controlled analgesic (PCA) meperidine infusions in a prospective randomized unblinded study for 72 hours postthoracotomy. Before induction of general anesthesia, patients received a bolus of meperidine, 1 mg/kg, and an infusion of meperidine, 0.33 mg/kg/hr, was started via either a lumbar epidural or intravenous catheter. Postoperatively, the meperidine infusion rates were titrated as needed for analgesia. In addition, the intravenous group received meperidine, 10 mg per dose, as required, from a patient-controlled analgesia pump. No other opioid was administered during the study period. Patients were studied for recovery of spirometric tests of pulmonary function, visual analog pain scores, sedation, arterial blood gases, meperidine dose requirements, radiographic pulmonary complications, and neurologic signs and symptoms. A subgroup of 10 patients (5 from each group) had venous blood samples drawn every 24 hours for 96 hours and assayed for serum meperidine and normeperidine concentrations. Epidural meperidine analgesia was associated with improved postthoracotomy pulmonary function, better analgesia scores, and lower meperidine dose requirements than intravenous PCA meperidine. There were no differences between the epidural versus intravenous PCA subgroups with respect to serum meperidine or normeperidine levels. Normeperidine levels greater than 300 ng/mL were associated with an increased incidence of shakiness and/or tremors. Meperidine provides satisfactory postthoracotomy analgesia via a lumbar epidural infusion. This analgesia is associated with improved recovery of postoperative pulmonary function when compared with an intravenous PCA meperidine infusion. PMID- 7780068 TI - Retrograde-delivered cardioplegia is not distributed equally to the right ventricular free wall and septum. AB - Right ventricular myocardial protection during cardiac surgery continues to be a challenge. Retrograde delivery of cardioplegia has been shown to perfuse left ventricular regions subtended by critical coronary stenosis and not adequately protected by antegrade delivery. However, the distribution of cardioplegia from the coronary sinus to the right ventricle remains in question. A reliable means for assessing such flow distribution intraoperatively is provided by contrast echocardiography. It was hypothesized that conventional use of coronary sinus catheters for retrograde cardioplegia delivery does not reliably perfuse the myocardial region subtended by the right coronary artery. Six patients scheduled to undergo elective coronary artery bypass surgery were evaluated with contrast echocardiography to determine the distribution of retrograde-delivered cardioplegia into the right ventricle. Sonicated Renografin-76 (Squibb Diagnostics, Princeton, NJ) was injected during retrograde delivery of cold crystalloid cardioplegia solution and continuous two-dimensional ultrasound imaging of the heart. On-line videodensitometric analysis was performed with a digital ultrasound system. The area under the curve and peak pixel intensity were determined for the anterior septum, the posterior septum, and the right ventricular free wall for each contrast injection. Recorded VHS videotape images of contrast-enhanced perfusion patterns were also reviewed and scored. On-line acoustic-densitometric analysis showed that right ventricular posterior and anterior septal peak pixel intensities were 4.8 +/- 3.2 and 7.3 +/- 1.5, respectively, compared with only 1.6 +/- 1.2 (p < or = 0.05) in the right ventricular free wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780069 TI - Comparison of vecuronium and meperidine on the clinical and metabolic effects of shivering after hypothermic cardiopulmonary bypass. AB - The use of vecuronium and meperidine on the clinical and metabolic effects of shivering in mechanically ventilated patients after hypothermic cardiopulmonary bypass (CPB) was compared. Twenty adult male patients undergoing cardiac surgery were randomized to meperidine, 25 to 75 mg (n = 10), or vecuronium, 0.1 microgram/kg (n = 10), for the treatment of shivering during postoperative rewarming. Vecuronium was continued as an infusion at 1.0 microgram/kg/min for 4 hours. Meperidine abolished shivering in 50% of patients with a 60% recurrence within 2 hours and did not correct acute respiratory acidosis when it occurred. Vecuronium uniformly abolished shivering, corrected acute respiratory acidosis, and improved mixed venous oxygen saturation (20% v 4%), decreased oxygen consumption (-32% v -7%) and decreased end-tidal carbon dioxide (-21% v -5%) significantly more than meperidine (p < 0.005). Meperidine administration caused a significant decline in systolic blood pressure (121.9 +/- 10.6 mmHg to 106.9 +/ 8.5 mmHg, p = < 0.02). The authors conclude that, during rewarming after hypothermic CPB, muscle relaxation with vecuronium reverses both the clinical and metabolic effects of shivering more reliably and effectively than repeated boluses of meperidine, and with greater hemodynamic stability. Control can be maintained by continuous infusion of vecuronium with concomitant sedation for up to 4 hours without prolonging intubation time. PMID- 7780070 TI - Determinants of postoperative hypothermia after normothermic cardiopulmonary bypass. AB - Inadvertent postoperative hypothermia in the cardiac surgical patient can have various adverse physiologic effects. Previous studies have investigated the relationship of patient, surgical, and anesthetic factors with postoperative hypothermia in patients undergoing noncardiac surgery. This study was designed to assess the relationship between postoperative hypothermia after normothermic cardiopulmonary bypass (CPB) for cardiac surgery and a variety of perioperative and patient factors. Fifty-six patients undergoing daytime elective or urgent cardiac surgery with warm (37 degrees C) CPB were studied. The following patient variables were included: age, weight, height, sex, history of previous cardiac surgery, and prebypass temperature. The following treatment factors were recorded: type of surgery, type and dose of anesthetic, use of airway humidifier, use of an intravenous (i.v.) fluid warmer, total volume of i.v. fluid administered during surgery, net fluid volume administered via CPB, total time spent on CPB, use of nitroglycerin, use of alpha-agonists during surgery, and elapsed time from end of CPB to end of surgery. Core temperature readings, as measured by a pulmonary artery catheter thermistor, were noted as follows: (1) on insertion of the pulmonary artery catheter; (2) after the patient was weaned from CPB; (3) within 30 minutes of intensive care unit (ICU) arrival; (4) 3 to 5 hours after ICU arrival; (5) 7 to 9 hours after ICU arrival; and (6) 11 to 13 hours after ICU arrival. Multiple linear regression and logistic regression for categorical variables with backward elimination were employed to determine the impact of all variables on lowest postoperative temperature. The lowest mean temperature occurred during CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780071 TI - Modification of the diuretic and natriuretic effects of a dopamine infusion by fluid loading in preoperative cardiac surgical patients. AB - An intravenous infusion of dopamine at 2.5 microgram/kg/min was administered for 40 minutes to anesthetized cardiac surgical patients, and their renal function was measured. Five patients had the usual preoperative regimen of reduced fluid intake for the night and morning before surgery (nonhydrated), and five patients received normal saline, 2 mL/kg/hr intravenously, for 6 hours before anesthesia (hydrated). Renal function (measured by urine output, sodium excretion, free water clearance, and fractional excretion of sodium) was similar immediately before starting the dopamine infusion. All four variables were significantly higher in the hydrated group after 10 minutes; this difference becoming maximal after 40 minutes. Twenty minutes after stopping the dopamine infusion, renal function was similar in the two groups. This study indicates that preoperatively fluid-restricted patients demonstrate powerful salt and water conservation with reduced natriuretic and diuretic responses to a low-dose dopamine infusion when compared with hydrated patients. Patients with adequate fluid loading and intravascular volume will demonstrate a marked natriuresis and diuresis in response to low-dose dopamine infusion. PMID- 7780072 TI - Oxygen transport and hemodynamics during retrograde whole-body perfusion. AB - The changes in oxygen transport and hemodynamics during retrograde whole-body extracorporeal perfusion (retro-ECC) were studied in six mongrel dogs. Oxygen consumption during retro-ECC, in which the blood flow rate was set at 25% and 50% of the flow during antegrade extracorporeal perfusion (ante-ECC), respectively, was relatively high compared with that during ante-ECC. These changes were caused by an increase in the oxygen extraction ratio to 71.5% +/- 8.2% and 51.2% +/- 12.4% during retro-ECC/25% and retro-ECC/50%, respectively. Thus, tissue perfusion was apparently well maintained by retrograde perfusion on the basis of the oxygen transport data. However, central venous pressure increased markedly to 29.5 +/- 11.6 mmHg and 56.2 +/- 24.5 mmHg during retro-ECC/25% and retro-ECC/50%, respectively, because of massive venous congestion caused by insufficient arterial return of perfused blood. The great venous compliance and increased systemic vascular resistance were the main causes of circulatory failure during retro-ECC. The risk of serious complications owing to the venous congestion must be considered during retrograde perfusion, especially during the clinical application of retrograde cerebral perfusion. PMID- 7780073 TI - Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients. AB - A retrospective study was performed to determine the impact of a coagulation and transfusion management program on blood utilization in 1,079 sequential patients for myocardial revascularization and open ventricle or combined procedures. Four hundred and eighty-eight patients (group 1) before, and 591 patients (group 2) after institution of thromboelastography (TEG)-guided coagulation were studied and compared for transfusion requirements, donor exposure, and the incidence of reoperation for hemorrhage. Group 2 patients had a significantly lower incidence of overall transfusion (78.5% v 86.3%) during hospitalization and in total transfusion in the operating room (57.9% v 66.4%). The incidence of each transfusion subtype was also significantly lower in group 2 patients. Actual total median donor exposure was 8 in group 1 patients and 6 exposures in group 2 patients. Mediastinal reexploration for hemorrhage was 5.7% before institution of TEG-based coagulation monitoring and 1.5% in TEG-monitored patients. Use of TEG monitoring before reexploration has decreased the cost and potential risk for patients undergoing CABG surgery. PMID- 7780074 TI - The use of thoracic epidural anesthesia in repair of an aortic coarctation. PMID- 7780075 TI - The use of halothane to treat severe bronchospasm after a unifocalization procedure. PMID- 7780076 TI - The Univent tube for airway management in combined ascending and descending thoracic aortic surgery. PMID- 7780077 TI - Drug management for coronary revascularization without cardiac standstill: the use of high-dose esmolol. PMID- 7780078 TI - Kearns-Sayre syndrome and cardiac anesthesia. PMID- 7780079 TI - Respiratory muscle loading and the work of breathing. PMID- 7780080 TI - Case 2--1995. Continuous retrograde cerebral perfusion as an adjunct to brain protection during deep hypothermic systemic circulatory arrest. PMID- 7780081 TI - Pro: pH-stat management of blood gases is not preferable to alpha-stat in patients undergoing brain cooling for cardiac surgery. PMID- 7780082 TI - Con: pH-stat management of blood gases is preferable to alpha-stat in patients undergoing brain cooling for cardiac surgery. PMID- 7780083 TI - An unusual transesophageal echocardiogram. PMID- 7780084 TI - Pediatric pain in the nineties. PMID- 7780085 TI - Is it possible to improve the shape of right double-lumen endobronchial tubes? PMID- 7780086 TI - Fibroblast growth factors and their receptors: an information network controlling tissue growth, morphogenesis and repair. AB - The stimulation of cellular metabolism by the nine fibroblast growth factors (FGFs) is mediated by a dual-receptor system. This comprises a family of four receptor tyrosine kinases (FGFR) and heparan sulphate proteoglycans (HSPG). The stimulation of cell division by FGFs has an obligate requirement for both partners of the dual-receptor system. The binding of the nine FGFs to the FGFRs is marked by a pattern of overlapping specificity despite alternative splicing events generating a large number of FGFR proteins. Thus many of the FGFR isoforms bind several FGFs. It is likely that each FGF requires a different pattern of sulphation within the heparan sulphate chains for binding. Therefore, the HSPG receptors may provide additional specificity, allowing a cell to fine tune its response to the FGFs present in the extracellular milieu. The HSPG receptors also control the availability of FGFs and hence regulate the transport of FGFs within a tissue. FGF-stimulated cell division would appear to have a mandatory requirement for the FGFs to be translocated to the nucleus via the cytosol after interacting with the dual-receptor system. The consequences of the potential direct action of FGFs in stimulating cell division are examined in the light of current models of signal transduction. PMID- 7780088 TI - Bibliographic update: hepatocyte growth factor. PMID- 7780087 TI - Growth factors in CNS repair and regeneration. AB - Traumatic central nervous system (CNS) injury is a significant clinical problem in the developed world. After injuries that penetrate into either the mature brain or spinal cord, damaged neurons initially begin to regrow, but this regeneration is aborted as a fibrotic scar is laid down within the wound. Reconnection of several neuronal pathways does not occur. Functional recovery from such injuries is therefore poor and morbidity severe, particularly for those patients with spinal cord damage. Although palliative measures are available to improve the quality of life, there is no accepted treatment to restore impaired sensory or motor function, so patients remain significantly and permanently debilitated. However, the rapid recent advances that have been made in our understanding of the underlying cellular and trophic pathology of such injuries offer the potential for development of novel therapies to control scarring, enhance neuron survival and stimulate axon regeneration, thereby promoting functional recovery. PMID- 7780089 TI - Trend of initial drug resistance of tubercle bacilli isolated from new patients with pulmonary tuberculosis and its correlation with the tuberculosis programme in Beijing. AB - SETTING: The tuberculosis control programme of Beijing. OBJECTIVE: To observe the trend of initial drug resistance of tubercle bacilli and to try to correlate it with the Beijing tuberculosis control programme. DESIGN: Susceptibility testing of randomly collected isolates of positive sputum culture from new patients with pulmonary tuberculosis without a history of prior antituberculosis therapy, in 1962 and continuously since 1978. Collection of treatment data from the Beijing tuberculosis control programme. RESULTS: The trend of initial drug resistance in Beijing began to decline in 1978. The Beijing tuberculosis treatment programme has been very successful, resulting in rapid reduction of prevalence of smear positive cases. CONCLUSION: It appears that the trend of initial drug resistance correlates with progress made in the implementation of the successful tuberculosis programme in Beijing. It is recommended that continuous observation of initial drug resistance be one of the indices of tuberculosis surveillance. PMID- 7780090 TI - Treatment of pulmonary disease caused by Mycobacterium kansasii: results of 18 vs 12 months' chemotherapy. AB - SETTING: Chest Clinic, Sant Pau Hospital, Barcelona, Spain. OBJECTIVE: To assess the therapeutic response of pulmonary disease due to Mycobacterium kansasii to 12 and 18 months of chemotherapy. DESIGN: 28 patients with criteria of pulmonary disease caused by M. kansasii not associated with HIV-infection were identified in our department in the period 1985-91 (24 male, 4 female, mean age 56 +/- 12 years). 14 patients were treated with rifampicin-isoniazid-ethambutol daily for 12 months (ethambutol only for the first 6 months), and 14 with the same regimen for 18 months. The follow-up after treatment was 12-30 months. RESULTS: All patients showed improvement of radiographic manifestation of disease and sputum conversion (mean time: 4.5 +/- 2 months). The adverse drug effects were minimal. No failures were detected, and only one patient (3.5%), in the group of 12-month chemotherapy, relapsed after finishing the treatment. CONCLUSIONS: Our findings suggest that pulmonary disease due to M. kansasii has an effective response to 12 month chemotherapy regimen and that it is not necessary to prolong the administration of ethambutol for more than 6 months. PMID- 7780091 TI - Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. AB - SETTING: Concomitant feeding and administration of antituberculosis medication has been proposed to increase compliance (by decreasing pyrazinamide associated nausea) and improve nutritional status. Food may however decrease the oral bioavailability of rifampicin and isoniazid. OBJECTIVE AND METHODS: A triple crossover pharmacokinetic study in 27 patients with tuberculosis (15 males and 12 females) compared the bioavailability of rifampicin, isoniazid and pyrazinamide without food (control) with that when taken with a high carbohydrate (CHO) or high lipid (LIPID) diet. RESULTS: the CHO diet decreased isoniazid bioavailability. The maximum measured drug concentration (Cm) was decreased by 20% (P = 0.0002) and the area under the concentration-time curve to 8 h (AUC8) by 19% (P = 0.01). The CHO diet increased the time to maximum measured drug concentration (Tmax) for rifampicin by 21% (P = 0.03). The LIPID diet decreased the Cm of isoniazid by 9% (P = 0.03). Individual patient bioavailability on each meal was compared to the no-food control. A decrease of Cm or AUC8 of greater than 20% was considered significant. The bioavailability of isoniazid and rifampicin was decreased by food in a high percentage (33-56%) of patients. CONCLUSION: Concomitant feeding may thus have an important adverse effect on the therapy of tuberculosis and the desirability of this practice is called into question. PMID- 7780092 TI - Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys. AB - SETTING: National tuberculin skin test surveys. OBJECTIVES: To review the operating characteristics of the tuberculin skin test, to ascertain the validity of estimating prevalence and risk of infection from tuberculin skin test surveys under various conditions, and to review constraints in the estimation of the magnitude of the tuberculosis problem in the community from such surveys. METHODS: This report utilizes hypothetical and selected real data obtained in regional and national surveys at various points in time to exemplify methodological issues. RESULTS: Risk of infection, the essence to be abstracted from tuberculin skin test surveys, theoretically allows for a comparison of the extent of transmission of tubercle bacilli in various populations. However, the conduct of tuberculin skin test surveys and the analysis and interpretation of their results are not free from important technical problems. Accurate estimation of infection prevalence is particularly vulnerable to the great variability of the test's specificity under various circumstances. Furthermore, the annual risk of infection has averaging characteristics that preclude a rapid assessment of changes in transmission patterns. Finally, estimates of infection risk do not necessarily provide a standardized parameter to derive incidence of infectious cases, because of variations in the quality of intervention and varying risks of progression from latent infection to overt tuberculosis. CONCLUSIONS: While tuberculin skin test surveys provide the currently most widely used means of assessing tuberculosis transmission patterns over prolonged periods of time in a community, results from such surveys must be interpreted with caution when accurate estimates of the tuberculosis problem are sought. PMID- 7780093 TI - Tuberculin sensitivity and the BCG scar in tuberculosis contacts. AB - SETTING: Tuberculosis clinic, St Vincents Hospital, Dublin. OBJECTIVE: To determine the influence of past BCG vaccination on tuberculin sensitivity in tuberculosis contacts. DESIGN: Prospective cohort study of tuberculin sensitivity using the Mantoux technique (5 TU). RESULTS: In 1050 contacts of 96 cases of tuberculosis, BCG scars were noted in 76% of the contacts. Approximately 50%, 30% and 20% of the contacts respectively had negative (0-4 mm), positive (5-14 mm) and strongly positive (15+ mm) Mantoux responses. The presence of a BCG scar was not found to significantly influence the degree of tuberculin sensitivity. The degree of tuberculin sensitivity increased after 20 years and decreased after 60 years of age. Contacts of sputum-positive cases of tuberculosis had larger Mantoux responses. CONCLUSIONS: The study suggests that age of the contact and sputum status of the index case are important determinants of the degree of tuberculin sensitivity. Attributing a 'positive' Mantoux response to past BCG vaccination may be encouraging a false sense of security in contacts recently exposed to an infectious case of tuberculosis. Contact management guidelines may need to be reviewed and perhaps modified to reflect this finding. PMID- 7780094 TI - Tuberculin sensitivity trends in Hellenic army recruits during the period 1981 91. AB - SETTING: The tuberculin skin test is widely used to define the tuberculous infection in the community. Serial representative tuberculin surveys demonstrate the trend of the risk of tuberculous infection. OBJECTIVE: The study of tuberculous infection in Hellenic army recruits for the purposes of BCG vaccination, which with chemoprophylaxis and early case-finding are the major strategies used for preventing tuberculosis (TB). DESIGN: We investigated tuberculin skin sensitivity on 544210 Hellenic Armed Forces recruits during 1981 91. The age of the subjects ranged between 18-28 years (mean 21 +/- 1.5 years). We used the Mantoux technique with tuberculin PPD-RT 23 with Tween 80, dose 2 IU (1/5000) of the Hellenic Pasteur Institute. Tuberculin skin reactions were examined by two experienced readers after 48 hours. Indurations < 5 mm were considered as negative reactions, > or = 10 mm as positive, and 5-9 mm as doubtful reactions. RESULTS: The results of the present study were compared to other studies undertaken in recruits during the period 1934-80. We found a decrease of positive reactions from 14.2% in 1981 to 6.8% in 1991. The mean annual reduction was 0.74%. The decline has continued since 1947, as previous studies during the period 1934-80 have shown. CONCLUSION: We conclude that the tuberculin reactivity in recruits of the Hellenic army, although still high in relation to other European countries and North America, is declining steadily. We predict that the number of positive reactions will fall to about 1% by the year 2000, assuming that the same trend continues. PMID- 7780095 TI - Serum soluble interleukin-2 receptor: a useful indicator of the clinical course in pulmonary tuberculosis. AB - SETTING: In tuberculosis both host protection and most pathogenic mechanisms depend on T lymphocytes. After activation by mycobacterial antigens, T cells both secrete interleukin-2 (IL-2) and express a high affinity receptor for this molecule (IL-2R) on their own surface. A soluble fraction of IL-2 receptor (sIL 2R), released from cell membrane, is detectable in serum and its concentration is known to be elevated in tuberculosis. OBJECTIVE: To ascertain the role of sIL-2R as an indicator of clinical evolution and response to antituberculosis treatment. DESIGN: A prospective study, in which we have measured serum sIL-2R in 52 patients (42 with active and 10 with inactive pulmonary tuberculosis) and in 36 healthy controls. In 20 patients, serum sIL-2R levels were measured serially throughout the treatment. Levels of sIL-2R were correlated to clinical and radiological parameters. RESULTS: Serum sIL-2R was significantly increased in patients with tuberculosis as compared to healthy subjects. Both the radiological findings and the clinical state of patients showed a good correlation with sIL 2R. All patients with normal values of sIL-2R 6 months after starting therapy had a favourable clinical evolution. CONCLUSION: Serum sIL-2R is a useful marker of the clinical state and evolution of patients with pulmonary tuberculosis. The detection of permanently high values beyond 3-6 months of treatment suggests that additional drugs or prolonged administration would be advisable in order to ensure full recovery. PMID- 7780097 TI - Distribution and characterization of beta-lactamases of mycobacteria and related organisms. AB - SETTING: The detailed distribution and precise features of mycobacterial beta lactamases urgently need to be elucidated. OBJECTIVE: To study the distribution pattern of beta-lactamases among mycobacteria, their enzymatic profiles and degree of contribution to the expression of drug resistance of some mycobacteria to beta-lactam antibiotics. DESIGN: Cell-associated beta-lactamase was measured by nitrocefin disc method. beta-lactamases obtained from some mycobacteria were studied for their substrate specificity, metal ion-dependency and isoelectric focusing (IEF) patterns. Changes in the minimum inhibitory concentrations (MICs) of beta-lactams for rapidly growing mycobacteria due to the combined use of tazobactam were measured. RESULTS: In slow growers, Mycobacterium tuberculosis complex possessed strong and M. kansasii showed strong to intermediate beta lactamase activity, while M. avium complex lacked such an activity. All the rapid growers possessed strong to intermediate activity. The beta-lactamases of test organisms including M. tuberculosis, M. kansasii, M. fortuitum etc, exerted both penicillinase and cephalosporinase activities and were not metalloenzymes. M. tuberculosis, M. kansasii, and M. smegmatis exhibited the species-specific IEF patterns of beta-lactamases. Tazobactam potentiated the in vitro antimicrobial activities of some beta-lactams against M. fortuitum and M. chelonae. CONCLUSION: Many mycobacteria possessed peculiar beta-lactamases and the enzymes were partly attributable to their drug resistance to certain beta-lactam antibiotics. PMID- 7780098 TI - Tracing as part of tuberculosis control in a rural Cambodian district during 1992. AB - SETTING: The rural Cambodian district of Banteay Meas, population 74,464. OBJECTIVE: To evaluate the effectiveness of a district based tracing program developed to improve tuberculosis control program treatment results. Specifically, to assess factors affecting patient non-adherence to therapy and return of patients to treatment. DESIGN: All patients started on treatment during 1992 were included. Standardized cohort analysis methods were applied to assess treatment outcome for all tuberculosis cases registered during Trimesters I-III. Absconders for the year were traced and followed as a separate cohort. Those returning to therapy were followed until the end of the study period in October 1993. RESULTS: Activity in 1992 included 171 admissions and 46 absconders. Of the 46, 57% were met at home. Among those met, 81% returned to treatment. Males absconded more than females even though females accounted for a majority of admissions. Socioeconomic factors (68%) were cited most often as the reason for non-adherence. Distance was not a factor. Cohort analysis showed improvement in the treatment completion rate (54.8% vs 69.2% vs 64%) coupled with a drop in the absconding rate (35.5% vs 25% vs 20%). Of the 21 patients returning, 76% have either completed or nearly completed treatment. CONCLUSION: These results support tracing as an effective means to improve patient adherence in rural Cambodia, thereby strengthening tuberculosis control programs at district level. PMID- 7780096 TI - In vitro activities of 2,2'-bipyridyl analogues against Mycobacterium avium and M. tuberculosis. AB - SETTING: Because of widespread emergence of resistant Mycobacterium tuberculosis and the high incidence of opportunistic infection caused by M. avium (MAC) in AIDS patients, there is an urgent need for new drugs against these organisms. OBJECTIVE: To evaluate the activity of newly synthesized 2,2'-bipyridyl analogues against MAC and M. tuberculosis. DESIGN: Susceptibility of MAC and M. tuberculosis to VUF-8514 and VUF-8842 were determined by both tube dilution method using 7H9 broth and radiometric (BACTEC) method using 14C-palmitic acid. RESULTS AND CONCLUSIONS: The MICs of 8514 against MAC and M. tuberculosis wee 1 microgram/ml and 0.5 microgram/ml respectively, while for 8842 the respective values were 8 micrograms/ml and 2 micrograms/ml. In general, the MBC values for both drugs were two-fold higher than their corresponding MIC values. However, both drugs exhibited high bactercidal activities against both organisms. The MICs of clinical isolates of both organisms were in the same range as reference strains; furthermore, two isolates of M. tuberculosis that showed resistance to rifampicin were found to be susceptible to 8514. Thus, these two bipyridyl analogues show great promise in chemotherapy of tuberculosis and M. avium infection. PMID- 7780099 TI - Isolation of Mycobacterium malmoense from the environment in Zaire. AB - Two strains of mycobacteria isolated from water and soil in Zaire were identified as Mycobacterium malmoense by biochemical tests and lipid analysis. Apart from the previously reported fatty acids characteristic of this species, both strains, as well as 5 clinical isolates of M. malmoense, contained 2,4-dimethyl-docosanoic acid. One of the environmental strains, with a glycolipid pattern II, additionally contained 2-methyltetradecanoic acid. The results confirm that M. malmoense may be subdivided in 2 sub-groups according to its lipid patterns. They also show that M. malmoense can be isolated from the environment which may be the source of the infection. PMID- 7780100 TI - Isolation of Mycobacterium chelonae in a bronchoscopy unit and its subsequent eradication. AB - SETTING: Contamination events with Mycobacterium chelonae in 7 patients undergoing bronchoscopy, out of a total of 100 patients in a 5-month period, were analysed. OBJECTIVE: To identify and assess the importance of factors thought to be relevant in the aetiology of these contamination events and by removing these factors, to eradicate the problem of continuing M. chelonae contamination. DESIGN: A retrospective analysis of the frequency of M. chelonae isolates from bronchoalveolar fluid, assessing the contribution of the following measures to the eradication of M. chelonae: (1) changes to the bronchoscopy unit's water supply; (2) insertion of bacterial filters; (3) installation of a new semi automated cleaning machine incorporating an ultrasound cycle; (4) staff training in correct use of the new equipment. RESULTS: Following the discontinuation of using tapwater in the cleaning process, the above changes resulted in complete eradication of contamination events, with no further events occurring in the following 12 months. CONCLUSION: Insertion of bacterial filters into the water supply, with the addition of a more sophisticated semi-automatic cleaning machine involving an ultrasound cycle in addition to conventional cleaning methods currently used, will help reduce or eradicate contamination events with M. chelonae in bronchoscopy units. PMID- 7780101 TI - Disseminated Mycobacterium genavense infection in Canadian AIDS patients. AB - Mycobacterium genavense is a recently described mycobacterial species which thus far has been identified only in persons with advanced HIV disease. It appears to be a rare pathogen with an undefined reservoir. We describe the first two cases of M. genavense infection in Canadian AIDS patients. The clinical presentation of fever and wasting with extremely low CD4 lymphocyte counts was indistinguishable from disseminated M. avium complex (MAC) infection. However, blood cultures in BACTEC 13A medium required a mean of 58 days (range 41-87) to detect growth of M. genavense in contrast to a mean of 10 days for MAC in our laboratory. M. genavense infection is underdiagnosed due to the lack of universal use of BACTEC liquid medium and the use of relatively short incubation times (only 6 weeks) by some laboratories. The value of antimycobacterial therapy for M. genavense is unknown, but anecdotal data suggest that treatment with a regimen appropriate for MAC may be beneficial. PMID- 7780102 TI - Mycobacterium malmoense in Italy. AB - A case of mycobacterial lymphadenitis due to Mycobacterium malmoense was recently diagnosed in a 5-year-old girl. The organism was isolated from pus and tissue fragments obtained by surgical excision of the affected nodes. This is the first documented case of human infection due to this organism in Italy. PMID- 7780103 TI - Ciprofloxacin-induced renal dysfunction in patients with mycobacterial lung infections. AB - 3 patients with mycobacterial lung infections, one due to Mycobacterium avium intracellulare and 2 due to M. tuberculosis, developed ciprofloxacin-induced acute renal dysfunction while receiving the drug together with other antimycobacterial agents. These episodes took place 8-10 days after commencement of therapy and recovered spontaneously after cessation of all antimycobacterial drugs for 2-8 weeks. No recurrence was noted when patients were restarted on regimens that did not contain ciprofloxacin. PMID- 7780104 TI - Oral tuberculosis: primary localisation in an elderly non-immunodepressed patient. AB - We report a case of oral tuberculosis in an elderly non-immunodepressed patient. We emphasize and discuss the main epidemiological and clinical aspects as compared with the more common pictures of the past. PMID- 7780105 TI - An unusual presentation: primary tuberculosis of the middle ear cleft. AB - Tuberculosis rarely affects the middle ear cleft; therefore, except for those working in close association with respiratory physicians, the disease is a curiosity and not often considered in the differential diagnosis of otorrhea. The diagnosis is thus made too late, with resulting complications such as irreversible hearing loss and facial nerve paralysis. A case report and review of the literature are presented, emphasizing that tuberculosis should be considered in the differential diagnosis of chronic ear infection. PMID- 7780106 TI - Compliance with tuberculosis treatment in a rural district. PMID- 7780107 TI - Hypersensitivity to multiple drugs streptomycin, rifampicin and ethambutol: an unusual presentation. PMID- 7780108 TI - The International Union Against Tuberculosis and Lung Disease model National Tuberculosis Programmes. PMID- 7780109 TI - The relationships between erythroblast denucleation and the nuclear matrix- intermediate filaments. AB - We present a novel approach for making cybrids. By introducing neo gene expression plasmids into rabbit reticulocytes, fusing the gene transferred reticulocytes with K562 cells and selecting in G418 selection medium, a cybrid strain K-RRneo was established. Whole mount TEM study demonstrated that after cybridization, there was a reorganization of the intermediate filaments which showed a tendency to differentiate towards reticulocytes. SDS-PAGE and western blot analysis verified the above observation, in which the vimentin blot pattern of the cybrids was similar to that of reticulocytes, but totally different from that of K562 cells. Using this model, we reaffirmed the hypothesis that the erythroid differentiation factor (EDF) might be responsible for erythroid differentiation as well as the initiation of denucleation. PMID- 7780110 TI - P-glycoprotein expression in primary breast cancer. AB - In a retrospective study, liquid nitrogen preserved specimens from 50 women with primary breast cancer, who underwent surgery at the Beijing Institute for Cancer Research between June, 1986 and September, 1988, were investigated. All patients under this study were staged in TNM II or later, involved with axillary lymph node metastasis, and treated with systemic postoperative adjuvant chemotherapy. The median length of follow-up was 69 months. The expression of P-glycoprotein was investigated by means of immunohistochemistry, using a monoclonal antibody C219 specifically against P-glycoprotein and avidin-biotin peroxidase method. Positive staining for P-glycoprotein was found in 23 (46%) of the 50 patients. The P-glycoprotein expression negative group fared better than the group that was P-glycoprotein positive in overall survival curves (p = 0.0008, by the generalized Wilcoxon test). The prognostic effect of P-glycoprotein expression remained statistically significant (p = 0.0007) after adjustment by multivariate analysis (Cox's model) for other prognostic factors. It is demonstrated that P glycoprotein expression is a significant and independent predictor of postoperative survival in breast cancer patients. The results of the present study suggest that P-glycoprotein expression might also influence the biological behavior of breast cancers. PMID- 7780111 TI - Effect of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo(a)pyrene. AB - Glycyrrhetinic acid (GA) is an active component of Glycyrrhiza uraleusis fisch. In this study, GA was found to inhibit ear edema and ornithine decarboxylase (ODC) activity induced by croton oil in mice. GA could also protect rapid DNA damage and decrease the unscheduled DNA synthesis induced by benzo(a)pyrene. The results demonstrate that GA has a potential cancer chemopreventive activity. PMID- 7780112 TI - The use of a shuttle plasmid to study nontargeted mutagenesis and its sequence specificity. AB - Intact pZ189 DNA was replicated in monkey kidney vero cells which had been pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The mutants were selected in E. coli MBM7070 and the mutation frequencies involving mutants with unchanged electrophoretic mobility of their plasmid DNA were scored. When compared to the spontaneous mutation frequency, the mutation frequencies were increased by 5.8 and 2.9-fold in cells pretreated with 0.2 and 2 mumol/L MNNG, respectively. The supF genes of these mutants were sequenced, and it was found that the types of base substitution and the sites of frameshifts differed from findings in studies of spontaneous and targeted mutagenesis. The results suggest that nontargeted mutagenesis occurs in mammalian cells and may have a sequence specificity. PMID- 7780113 TI - The regulatory effect of nucleoside diphosphate kinase on G-protein and G-protein mediated phospholipase C. AB - The effect of nucleoside diphosphate kinase (NDPK) on the activity of guanine nucleotide regulatory protein (G-protein) mediated phospholipase C (PLC) and on the [35S] GTPT tau S binding of G-protein was investigated in this work in order to demonstrate the mechanism behind the regulation of G-protein and its effector PLC by NDPK. The stimulation of PLC in turkey erythrocyte membrane by both GTP and GTP tau S indicated that the PLC stimulation was mediated by G-protein. NDPK alone stimulated PLC activity, as well as the stimulation in the presence of GTP and GDP, in a dose-dependent manner. However, NDPK inhibited GTP tau S-stimulated PLC. Furthermore, NDPK inhibited [35S]GTP tau S binding of purified Gi-protein in a non-competitive manner. A hypothesis implying an important role of direct interaction of G-protein and NDPK in the regulation of their functions is suggested and discussed. PMID- 7780114 TI - The measurement and application of TSH-IRMA levels among different age groups in areas with iodine deficiency disorders. AB - Using immunoradiometric TSH assay (TSH-IRMA) to measure whole blood TSH levels spotted onto filter paper, we compared TSH levels among different age groups (neonates, < 1 yr infants, schoolchildren aged 7 to 14 yrs, adults, pregnant women and reproductive-age women) in Guiyang, where iodine deficiency has long been a problem. The results showed: 1) The percentage of subjects with TSH levels equal to or greater than 5 mIU/L in the neonate group was 38.9% while the percentages in the other groups were 0-3.3% (P < 0.01); 2) The TSH levels of the neonates were inversely related to the urinary iodine values of their mothers (pregnant women). (r = -0.5, P < 0.01); 3) 97.6% of the inhabitants in Guiyang ingested salt with less than 20 mg/kg iodine. The results indicate that iodine deficiency remains a problem in Guiyang. Neonates are the only ideal population for monitoring iodine deficiency. PMID- 7780115 TI - Rapid HLA-DRB1 generic typing by PCR-SSP method. AB - We report a simple and rapid HLA-DRB1 generic typing method, PCR-SSP, which is practical and inexpensive. We use 9 sequence-specific primers and 2 group specific primers to define the HLA-DRB1 specificities DR1, DR2, DR3, DR4, DR5, DR6, DR7, DR8, DR9 and DR10. The HLA DR3, DR5, DR6 and DR8 can be amplified by the two primers of DR3568 and DRB1. The DR6 specificity can be identified by excluding the DR3, DR5 and DR8 when the DR3568 are positive. Any individuals can be typed with some exception: the three pairs of phenotype DR3/DR3 and DR3/DR6, DR5/DR5 and DR5/DR6, DR8/DR8 and DR8/DR6 cannot be discriminated from each other. We typed 106 unrelated healthy people from Beijing locations in two weeks. We think this typing method is suitable to replace the error-prone serologic HLA-DR tests in routine clinical practice, including the prospective typing of cadaveric organ donors. PMID- 7780116 TI - Significance of flow cytometry in the diagnosis and treatment of bladder tumors. AB - The results of application of flow cytometry (FCM) in analysis of 139 bladder irrigations of DNA contents in tumor cells from 52 cases of bladder tumors are reported. A comparison was made between this assay and cytological examinations as well as pathological grading. The results suggested that the accuracy of cytological analysis was apparently lower than the cell DNA measurement by flow cytometry, the higher the tumor pathological grading and the deeper the infiltration, the higher the heteroploid DNA contents in the tumor cells. Treatment of high heteroploid bladder tumor required radical cystectomy while the efficiency of simple electrosection or partial cystectomy appeared inferior. When FCM and the bladder tumor pathological grading had a high degree of correlation, especially in the high grading tumor, recurrence was high even when chemical treatment with bladder instillation of BCG was adopted. However, FCM cannot substitute for cystoscopy. PMID- 7780117 TI - Senile osteoporosis and hip fracture. AB - A randomized block design was used to compare the Singh index, the cortical index of the femoral neck and the lateral cortical width of the femur of a group of patients with femoral neck fracture, a group with intetrochanteric fracture, and a normal control group among a total of 102 postmenopausal women. The three indices in fracture group were very significantly (P < 0.01) or significantly (P < 0.05) different from those in the normal control subjects. The importance of osteoporosis in hip fracture of the aged is confirmed. Radiographic measurement of bone mass was found to have some predictive value for the risk of hip fracture. PMID- 7780118 TI - Mosaicism confined to placenta in pregnancies with adverse outcome. AB - Chorionic villi and fetal tissues from 50 pathological human conceptions at gestational weeks 9-40 were cultured and cytogenetically analyzed to explore the existence of chromosomal mosaicism confined to the extraembryonic tissues and to clarify the relationship between confined placental mosaicism and adverse outcome of pregnancy. Chorionic villi and fetal tissues from 12 second trimester gestations terminated for social reasons served as a control group. In two pathological gestations, true mosaicism was found exclusively in chorionic cells and could not be confirmed in cells derived from the fetal tissues. One of these was severely growth retarded. Concordant results were obtained in all other cases. PMID- 7780119 TI - Pre-exposure of mice to low dose or low dose rate ionizing radiation reduces chromosome aberrations induced by subsequent exposure to high dose of radiation or mitomycin C. AB - The phenomenon of cytogenetic adaptive and cross-adaptive response induced by low dose irradiation and chemical mutagen in mice is described. We found, firstly, that adaptation can be induced by acute low dose X-irradiation (0-100 mGy). Secondly, a cross-adaptation can occur between X-irradiation and mitomycin C (MMC). And finally, mice pre-exposed to chronic low dose rate 60Co-Gamma irradiation (0-226.0 mGy/day) are less susceptible to chromosome aberration induced by subsequent acute higher X-irradiation. Therefore, our data suggest that radioadaptive response depends on dose, dose rate and time interval. Possible mechanisms are also discussed. PMID- 7780120 TI - Experience in treating secondary systemic mycotic infection after severe burns associated with electric injury. PMID- 7780121 TI - A comparative study of imovane and estazolam treatment on sleep disturbances. AB - Twenty-six patients with sleep disturbances who had completed therapy with hypnotics were observed under single-blind and self-comparable method for 7 days each. We found that patients treated with imovane or estazolam had no statistical differences with respect to sleep time onset, total sleep time, nocturnal awakening, feeling after awakening, dream, drug side effects and sleep quality. Imovane performed better than estazolam in sleep time onset and total sleep time. From this study, imovane can be recommended as a new hypuotic to treat patients with sleep disturbances. PMID- 7780123 TI - The interrelationship between tumor cells' electrophoretic mobility, adhesive and invasive abilities, and their metastatic potential. AB - Investigations on the relationship between some tumor cell properties and their metastatic potential using different clones from two tumor cell lines are reported. CNE2L2 (highly metastatic) and CNE2L4 (low metastatic) clones were isolated from human nasopharyngeal carcinoma CNE-2Z cell line. LA1, LAD and LA5 clones were isolated from mouse pulmonary adenocarcinoma offLA795 cell line with different metastatic potentials. The results from both cell lines showed that the metastatic potential of tumor cells positively correlated with electrophoretic mobility rate, adhesion with endothelial cells and in vitro and in vivo invasiveness, and negatively correlated with self-adhesion and adhesion to fibroblast cells. The data further confirmed the relationship between these factors and the metastatic potential of tumor cells. PMID- 7780122 TI - Analysis of C-Ha-ras gene amplification and mutation in laryngeal carcinoma. AB - In order to study the altered molecular events during laryngeal carcinogenesis and elucidate the role of Ha-ras oncogene amplification and mutation, we have examined their profile by polymerase chain reaction (PCR) and selective oligonucleotide hybridization. We analyzed the mutational status of codon 12 of Ha-ras in 22 laryngeal carcinomas and 10 normal tissues, and found that 7 of 22 laryngeal carcinomas contained a Ha-ras mutation at codon 12. The frequency of mutation was 32%. None of the normal tissues revealed mutation. Moreover, no amplification was found in cancers when compared to the normal. Our findings indicated that the activated Ha-ras gene existed in laryngeal carcinoma, and activation of the Ha-ras gene by mutation at codon 12 might play a key role in laryngeal carcinogenesis. PMID- 7780124 TI - Diagnosis and surgical treatment of bronchogenic cysts. AB - Between 1974 and 1993, 22 patients with bronchogenic cysts were operated on in our hospital; there were 14 men and 8 women, ranging in age from 11 to 62 years. The cyst locations were mediastinal in 13 (59.1%) and intrapulmonary in 9 (40.9%). There were symptoms (chest pain and recurrent bronchiolitis) in 20 patients (91%). The preoperative complications included infection in the lung and in the cyst and dysphagia due to esophageal compression. Chest pain was the main symptom in mediastinal cyst and recurrent infection of lung in intrapulmonary cyst. Plain chest radiograms showed that a round shadow, occasional air-fluid levels, and peripheral calcification may be found in cysts. An operation is the best treatment for cysts. All cysts were completely excised. No postoperative complications, late complications, or recurrence developed in our patients. PMID- 7780125 TI - The treatment of severe acquired aplastic anemia. PMID- 7780126 TI - Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. AB - The TNF receptor superfamily members are all type I membrane glycoproteins with typical homology in the extracellular domain of variable numbers of cysteine-rich repeats (overall homologies, 25% to 30%). In contrast, the TNF ligand superfamily members (with the exception of LT alpha) are type II membrane glycoproteins with homology to TNF in the extracellular domain (overall homologies, 20%). TNF and LT alpha are trimeric proteins and are composed of beta-strands forming a beta jellyroll. The homology of the beta-strand regions for the TNF ligand superfamily members suggest a similar beta-sandwich structure and possible trimeric or multimeric complex formation for most or all members. A genetic linkage, as evidence for evolutionary relatedness, is found by chromosomal cluster of TNFR p80, CD30, 4-1BB, and OX40 for 1p36; TNFR p60, TNFR-RP, and CD27 for 12p13; TNF, LT alpha, and LT beta for 6 (MHC locus); CD27L and 4-1BBL for 19p13; and FASL and OX40L for 1q25. Of the TNF ligand superfamily, TNF, LT alpha, and LT beta and their receptors (TNFR p60, TNFR p80, and TNFR-RP) interact in a complex fashion of cross-binding. However, the other family members presently have a one ligand/one receptor binding principle (CD27/CD27L, CD30/CD30L, CD40/CD40L, 4 1BB/4-1BBL, OX40/gp34, and FAS/FASL). In general, the members of the TNF ligand superfamily mediate interaction between different hematopoietic cells, such as T cell/B cell, T cell/monocyte, and T cell/T cell. Signals can be transduced not only through the receptors but also through at least some of the ligands. The transduced signals can be stimulatory or inhibitory depending on the target cell or the activation state. Taken together, TNF superfamily ligands show for the immune response an involvement in the induction of cytokine secretion and the upregulation of adhesion molecules, activation antigens, and costimulatory proteins, all known to amplify stimulatory and regulatory signals. On the other hand, differences in the distribution, kinetics of induction, and requirements for induction support a defined role for each of the ligands for T-cell-mediated immune responses. The shedding of members of the TNF receptor superfamily could limit the signals mediated by the corresponding ligands as a functional regulatory mechanism. Induction of cytotoxic cell death, observed for TNF, LT alpha, CD30L, CD95L, and 4-1BBL, is another common functional feature of this cytokine family. Further studies have to identify unique versus redundant biologic and physiologic functions for each of the TNF superfamily ligands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7780127 TI - Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V. AB - Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506 FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid-dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506-FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC. PMID- 7780128 TI - Molecular detection of the (2;5) translocation of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction. AB - The t(2;5)(p23;q35) translocation was initially identified in cases of anaplastic large-cell lymphoma (ALCL) that expressed the Ki-1 (CD30) antigen. We have recently cloned this translocation and shown it to encode a chimeric product consisting of the N-terminal portion of a nonribosomal nucleolar phosphoprotein, nucleophosmin (NPM), from chromosome 5, fused to the kinase domain of a novel transmembrane tyrosine-specific protein kinase, anaplastic lymphoma kinase (ALK), from chromosome 2. To better define the spectrum of lymphomas that contain this translocation, we have analyzed 70 cases of non-Hodgkin's lymphoma (NHL) for expression of the t(2;5)-derived NPM/ALK chimeric message by reverse transcriptase-polymerase chain reaction (RT-PCR). Using a previously described set of oligonucleotide primers, NPM/ALK chimeric transcripts were detected in 21 of 22 cases that contained the t(2;5) by cytogenetic analysis and in 10 of 48 cases that either lacked evidence of the t(2;5) or had unsuccessful cytogenetics. In all but 1 case, the NPM/ALK PCR products were of identical size and sequence, suggesting that the genomic chromosome breaks are clustered in a single intron in both NPM and ALK. The NPM/ALK-expressing cases were not confined to NHLs with anaplastic morphology and included 15 ALCLs, 6 immunoblastic lymphomas, and 10 diffuse large-cell lymphomas. Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. Thus, neither anaplastic morphology nor the expression of CD30 accurately predicted the presence of this molecular genetic subtype of lymphoma. PMID- 7780129 TI - Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma. AB - Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL 10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL 10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis. PMID- 7780130 TI - p15ink4B and p16ink4 gene inactivation in acute lymphocytic leukemia. AB - Malignant cells from 52 children with acute lymphocytic leukemia (ALL) were investigated for inactivation of the p15ink4B and p16ink4 genes and other genetic alterations on chromosome 9p21. Homozygous deletions of the p15ink4B and/or the p16ink4 genes were detected in 16 cases and a further 9 cases showed evidence of allelic loss either by hemizygous deletion or loss of heterozygosity (LOH) for 9p21 markers. Most cases had loss of both genes, but 5 patients had lost only p16ink4 and 2 cases had homozygous loss of p15ink4B only. Sequence analysis of all exons of p15ink4B and p16ink4 was performed in patients with hemizygous deletions or LOH for 9p21 markers. A frame shift mutation of p16ink4 exon 1 was shown in 1 case, whereas all other clones carried the wild-type sequence of p15ink4B and p16ink4 in the remaining allele. The data suggest that both the p15ink4B and p16ink4 genes can be inactivated in ALL. The existence of a hitherto undefined tumor-suppressor gene on chromosome 9p cannot be ruled out. PMID- 7780131 TI - Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23). AB - A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans. PMID- 7780132 TI - Thrombopoietin induces tyrosine phosphorylation and activation of the Janus kinase, JAK2. AB - Thrombopoietin (TPO) is a recently characterized growth and differentiation factor for megakaryocytes and platelets that exerts its effects via the receptor, c-MpI. This receptor is a member of the hematopoietin receptor superfamily and is essential for megakaryocyte maturation; however, the molecular mechanisms of TPO and c-MpI action have not been elucidated. Recently, the Janus kinases have emerged as important elements in signaling via this family of receptors. In this report, we show that, in the M07e megakaryocytic cell line, which expresses c-MpI and proliferates in response to TPO, TPO induces phosphorylation of a number of substrates between 80 and 140 kD. Specifically, we show that stimulation with TPO induces the rapid tyrosine phosphorylation of a 130-kD protein that we identify as the Janus kinase, JAK2. However, no detectable tyrosine phosphorylation of JAK1, JAK3, or TYK2 was observed. TPO also induced activation of JAK2 phosphotransferase activity in vitro. Taken together, these data indicate that JAK2 likely plays a key role in TPO-mediated signal transduction. PMID- 7780133 TI - Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. AB - IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupled to the monoclonal antihuman CD22 antibody, RFB4. This study determined the maximally tolerated dose (MTD) of this immunotoxin (IT) administered as a continuous 8-day infusion to 18 patients with B-cell lymphoma (30% CD22+ tumor cells) over 8 days. The MTD was 19.2 mg/m2/192 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as dose-limiting toxicity (DLT) at 28.8 mg/m2/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT concentrations greater than 1,000 ng/mL and the absence of circulating tumor cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial responses, 3 minor responses, 6 stable disease, and 3 progression of disease were observed. The mean maximal serum concentration (Cmax) in initial courses at the MTD (19.2 mg/m2) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m2/192 h, the Cmax was highly variable (n = 11; mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human antimouse or antiricin antibodies developed in 6 of 16 (37.5%) patients after one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did not correlate with toxicity but decreased soluble interleukin-2 receptor concentrations correlated with clinical response. Comparison to a prior study with the same IT administered by intermittent bolus infusions (Amlot et al, Blood 82:2624, 1993) suggests similar clinical response, toxicity, and immunogenicity. PMID- 7780134 TI - Cloning and expression of unique murine macrophage colony-stimulating factor transcripts. AB - Cocultivation of cells from the gamma-irradiated D2XRII murine bone marrow stromal cell line with an interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent hematopoietic progenitor cell line FDC-P1JL26 stimulates the emergence of factor-independent hematopoietic cell sublines. Several lines of evidence suggested that M-CSF or a protein antigenically related to M-CSF, termed leukemogenic stromal factor (LSF), that was expressed by D2XRII cells may have played a role in the emergence of the factor-independent sublines. In an effort to isolate a factor antigenically related to M-CSF, molecular clones were isolated from a D2XRII cDNA library that hybridized to a mouse M-CSF genetic probe. Two of these molecular clones, designated 60.8.2 and 6452, contained an 885-bp deletion in the M-CSF coding region. Such a cDNA clone has not been previously described in the mouse, but a cDNA clone homologous to it has been isolated from a human pancreatic tumor cell line, MIA-PaCa-2. Three transcripts (4.8, 3.4, and 1.8 kb) were detected that hybridized to an oligonucleotide probe that was specific to RNA transcripts containing the 60.8.2 deletion. The level of the 1.8-kb transcript was not detectably induced by ionizing irradiation; however, the levels of the 4.8-kb and 3.4-kb transcripts and two other M-CSF transcripts of sizes to 4.4 kb and 2.3 kb showed a 1.4- to 2.2-fold increase after gamma irradiation. Reverse transcription-polymerase chain reaction showed that the deletion-specific transcript(s) was detected in multiple mouse bone marrow stromal cell lines and in normal mouse tissues. The present studies establish the existence of an increased spectrum of murine M-CSF transcripts in bone marrow stromal cells and other tissues. This complexity of transcripts along with their increased accumulation after irradiation provides additional evidence for a role of proteins encoded by M-CSF transcripts in the response of bone marrow stromal cells to ionizing irradiation. PMID- 7780135 TI - Interleukin-13 selectively suppresses the growth of human macrophage progenitors at the late stage. AB - Interleukin-13 (IL-13) is a pleiotropic cytokine that inhibits the production of inflammatory cytokines of monocytes. We investigated the effects of IL-13 on the clonal growth of human hematopoietic progenitors. IL-13 alone did not support any colony formation. IL-13 markedly suppressed macrophage colonies that were formed in the presence of IL-3 and erythropoietin, granulocyte-macrophage colony stimulating factor, or macrophage colony-stimulating factor. Macrophage colony cells showed dendritic cell-line morphology and cellular aggregates. IL-13 did not affect granulocyte colony and erythroid burst formation. Delayed addition of IL-13 and replating onto the culture dishes with IL-13 showed that macrophage colony formation was suppressed during days 8 and 14 of culture. These results indicate that IL-13 affects the growth of the late stage of committed macrophage progenitors. Single-cell culture of isolated CD34+CD33+ cells with IL-13 confirmed that macrophage colony formation was significantly suppressed. These results show that IL-13 directly suppresses the proliferation of differentiating macrophages. In addition, these suppressive effects of IL-13 were synergistic with IL-4. Furthermore, in the liquid culture of bone marrow cells in the presence of IL-13, the number of CD14 (monocyte-macrophage antigen)-positive cells decreased and CD18 (LFA-1 beta)-positive cells increased. It is concluded that IL-13 affects the growth of the late stage of macrophage precursors as well as mature monocytes. Induction of differentiation of human monocytes may be correlated with the suppression of their progenitors. PMID- 7780136 TI - Purification and characterization of a C5a-inactivating enzyme from human peritoneal fluid. AB - Earlier work has suggested that familial Mediterranean fever, an inherited disorder characterized by sporadic episodes of inflammation involving the pleural and peritoneal cavities and the joints, is caused by the lack of a C5a inactivator normally found in serosal fluid. We have purified this inactivator from ascites fluid and obtained a protein of molecular weight 53 to 56 kD with a specific activity 10,000-fold greater than the crude material. On Western blot, an inhibitory antibody recognized a single antigenic species at the same molecular weight. The enzyme had no activity against denatured bovine serum albumin. With recombinant C5a as substrate, the Km and Vm were 3.4 mumol/L and 52 nmol C5a/min/mg protein, respectively. PMID- 7780137 TI - Studies on the acute release of tissue-type plasminogen activator from human endothelial cells in vitro and in rats in vivo: evidence for a dynamic storage pool. AB - The process of acute release of tissue-type plasminogen activator (tPA) is important in locally speeding up fibrinolysis. Using a sensitive enzyme-linked immunosorbent assay for tPA, we investigated the acute release of tPA from cultured human umbilical vein endothelial cells. The addition of thrombin (0.003 to 3 NIH U/mL) caused the dose-dependent release of noncomplexed, enzymatically active tPA into the medium. The amount of tPA released into the medium by thrombin was similar to the difference in the amounts of tPA present in extracts from thrombin-treated cells and control cells. The process of acute release of tPA was complete in 1 minute, whereas the concomitant release of von Willebrand factor into the medium was slightly slower (maximum after 3 minutes). By increasing (c.q. decreasing) tPA synthesis, it was found that the amount of tPA constitutively secreted, the amount acutely released, and the amount in cell extracts were increased (c.q. decreased) to the same extent. The same relation was found in vivo. When rats were pretreated with cholera toxin or retinoic acid to increase tPA synthesis, plasma levels of tPA were increased, whereas acute release of tPA, as induced by bradykinin, was increased to the same extent. Acutely released tPA and constitutively secreted tPA were liberated from different pathways in human umbilical vein endothelial cells; tPA had, relative to the in vivo situation, a short residence time in the acutely releasable pathway. PMID- 7780138 TI - Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. AB - Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect. PMID- 7780139 TI - Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. AB - Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of beta-chain containing isoforms of C4b-binding protein (C4BP beta+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S deficient families. In normal relatives (n = 190), protein S correlated well with C4BP beta+, with free protein S (96 +/- 23 nmol/L) being equal to the molar excess of protein S (355 +/- 65 nmol/L) over C4BP beta+ (275 +/- 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 +/- 50 nmol/L) and C4BP beta+ (228 +/- 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 +/- 10 nmol/L). Free protein S levels were distinctly low in protein S deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfils the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BP beta+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S deficient members, suggesting that the concentration of C4BP beta+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BP beta+. PMID- 7780140 TI - Autocrine interleukin-1 beta regulates both proliferation and apoptosis in EL4 6.1 thymoma cells. AB - We demonstrate here that EL4-6.1 cells, a mouse thymoma that expresses high levels of membrane interleukin (IL)-1 receptors, produce IL-1 beta as an autocrine regulatory factor. Endogenous IL-1 beta sustains both proliferation and apoptosis: during the exponential phase, it mainly promotes proliferation, while during the plateau phase of cell growth, it induces death by apoptosis. Additionally, we show that exogenous IL-1 beta added to EL4-6.1 cells in lag phase induces apoptosis in a portion of the cells and proliferation in the remaining cells. Therefore, IL-1 beta can exert two completely opposite effects on a single cell type, depending on the state of the target cell. PMID- 7780141 TI - Retinoids downregulate both p60 and p80 forms of tumor necrosis factor receptors in human histiocytic lymphoma U-937 cells. AB - Because retinoids are known to modulate the growth and differentiation effects of tumor necrosis factor (TNF), we investigated the effect of all-trans-retinoic acid (RA) on the cell surface expression of TNF receptors in human histiocytic lymphoma U-937 cells. RA decreased the specific binding of 125I-labeled TNF to these cells in a dose- and time-dependent manner. The maximal decrease occurred when cells were treated with 1 mumol/L RA for 24 hours at 37 degrees C. Scatchard analysis of the binding indicated that the decrease by RA was caused by a decrease in receptor number and not by a decrease in affinity. The downmodulation of TNF receptors was also confirmed by covalent receptor-ligand cross-linking studies. Receptor-mediated internalization of the ligand was also found to be decreased on treatment of cells with RA. Northern blot analysis also indicated a decrease in the transcript of the receptor. By using antibodies specific to either the p60 or p80 form of the TNF receptor, we found that both receptors were downregulated by RA. RA treatment also decreased TNF receptors on acute monocytic leukemia cell line THP-1. Other analogues of RA, specifically 9-cis-RA, (E)-4-[2 (5,6,7,8- tetrahydro-2-naphthalenyl)-1-propenyl]-benzoic acid (TTNPB), and 3 methyl-TTNPB, which differ in their specificity towards different RA receptors, were also active in downregulating TNF receptors. 3-Methyl-TTNPB, which is more specific for the RXR form of the RA receptor, was found to be most potent. The downregulation of TNF receptors by RA correlated with the downmodulation of the antiproliferative effects of TNF against U-937 cells. Overall, our results indicate that RA downmodulates both the p60 and p80 form of the TNF receptor on cells of myeloid origin, which correlates with the cellular response. PMID- 7780142 TI - Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. 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 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL 1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome. PMID- 7780143 TI - Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism. AB - Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL-7, or CD2 MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output. PMID- 7780144 TI - Inhibition of CD26 enzyme activity with pro-boropro stimulates rat granulocyte/macrophage colony formation and thymocyte proliferation in vitro. AB - CD26 dipeptidyl peptidase (DPPIV) is involved in the regulation of proliferation of some hematopoietic and T-lineage cells. Here, we show that Pro-boropro a potent inhibitor of DPP activity has a costimulating effect in hematopoietic colony assays for macrophage and, to a lesser extent, for granulocyte colonies and has a stimulating effect in organ cultures of immature thymocytes. Based on these and other evidences, we propose that the mechanism by which CD26 regulates proliferation is associated with its DPP activity. PMID- 7780146 TI - All-trans retinoic acid and cyclic adenosine monophosphate cooperate in the expression of leukocyte alkaline phosphatase in acute promyelocytic leukemia cells. AB - Treatment of acute promyelocytic leukemia (APL) blasts with cyclic adenosine monophosphate (cAMP) analogs, in combination with all-trans retinoic acid (ATRA), results in the upregulation of the expression of leukocyte alkaline phosphatase (LAP), a marker for the differentiation of the granulocyte. The synergistic interaction between the cyclic nucleotide analogs and the retinoid is not unique to APL cells, as it is observed also in the peripheral granulocytes of chronic myelogenous leukemia (CML) patients. The molecular mechanisms underlying LAP induction were studied in NB4, an immortalized APL cell line. Induction of LAP enzymatic activity is dependent on the time of exposure and on the concentrations of dibutyryl-cAMP or 8-bromo-cAMP and ATRA, two factors that influence the kinetics of appearance of detectable levels of the enzyme. Augmentation of LAP levels by ATRA and cAMP is the result of both transcriptional and early posttranscriptional events and requires de novo protein synthesis. LAP induction correlates with augmentation in the levels of the type I catalytic subunit of cAMP-dependent protein kinase transcript and with granulocytic differentiation. The transcriptional component of the process leading to increased LAP gene expression was reproduced in its main features by transient transfection experiments performed in COS-7 cells using the normal retinoic acid receptor type alpha (RAR-alpha) or the APL-specific aberrant form (PML-RAR) and the upstream promoter of the liver/bone/kidney (L/B/K)-type alkaline phosphatase gene. The promoter is upregulated by treatment with ATRA, and this upregulation is further increased by cAMP analogs. PMID- 7780145 TI - Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses. AB - In chronic B-cell leukemias, fluorescence in situ hybridization has greatly improved the ability to detect certain chromosomal aberrations, as cells in all phases of the cell cycle are analyzed. To obtain a comprehensive view of chromosomal gains and losses, we applied the recently developed technique of comparative genomic hybridization (CGH) to 28 patients with chronic B-cell leukemias. CGH results were compared with those obtained by chromosome banding analysis and interphase cytogenetics. In 19 of the 28 cases, chromosomal imbalances were detected, including amplified DNA sequences in three instances. The most common aberrations included gains of chromosomal material on 8q and 12 as well as losses of 6q, 11q, 13q, and 17p. In 13 cases, CGH revealed chromosomal gains and losses not detected by banding analysis. In 8 of these 13 cases, discrepancies were further investigated using other methods, and in all instances, the CGH findings were confirmed. A limitation of detecting small deleted regions by CGH was found in one example of 18p. In conclusion, our data show that the results of banding analysis in chronic B-cell leukemias often do not reflect the chromosomal changes in the predominant cell clone. This may be one explanation for the as yet poor correlation between cytogenetic findings and clinical course in this group of neoplasms. PMID- 7780147 TI - Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages. AB - The bone marrow microenvironment supports and regulates the proliferation and differentiation of hematopoietic cells. Dysregulated hematopoiesis in chronic myelogenous leukemia (CML) is caused, at least in part, by abnormalities in CML hematopoietic progenitors leading to altered interactions with the marrow microenvironment. The role of the microenvironment itself in CML has not been well characterized. We examined the capacity of CML stroma to support the growth of long-term culture-initiating cells (LTC-IC) obtained from normal and CML marrow. The growth of normal LTC-IC on CML stroma was significantly reduced compared with normal stroma. This did not appear to be related to abnormal production of soluble factors by CML stroma because normal LTC-IC grew equally well in Transwells above CML stroma as in Transwells above normal stroma. In addition, CML and normal stromal supernatants contained similar quantities of both growth-stimulatory (granulocyte colony-stimulating factor (CSF), interleukin 6, stem cell factor, granulocyte-macrophage CSF, and interleukin-1 beta) and growth-inhibitory cytokines (transforming growth factor-beta, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha). The relative proportion of different cell types in CML and normal stroma was similar. However, polymerase chain reaction and fluorescence in situ hybridization studies showed the presence of bcr-abl-positivo cells in CML stroma, which were CD14+ stromal macrophages. To assess the effect of these malignant macrophages on stromal function, CML and normal stromal cells were separated by fluorescence-activated cell sorting into stromal mesenchymal cell (CD14-) and macrophage (CD14+) populations. CML and normal CD14- cells supported the growth of normal LTC-IC equally well. However, the addition of CML macrophages to normal or CML CD14- mesenchymal cells resulted in impaired progenitor support. This finding indicates that the abnormal function of CML bone marrow stroma is related to the presence of malignant macrophages. In contrast to normal LTC-IC, the growth of CML LTC-IC on allogeneic CML stromal layers was not impaired and was significantly better than that of normal LTC-IC cocultured with the same CML stromal layers. These studies demonstrate that, in addition to abnormalities in CML progenitors themselves, abnormalities in the CML marrow microenvironment related to the presence of malignant stromal macrophages may contribute to the selective expansion of leukemic progenitors and suppression of normal hematopoiesis in CML. PMID- 7780148 TI - The PML gene encodes a phosphoprotein associated with the nuclear matrix. AB - The t(15;17)(q22;q12) translocation is the cytogenetic hallmark of acute promyelocytic leukemia (APL). The PML and retinoic acid receptor-alpha (RAR alpha) transcription factor genes are involved at translocation breakpoint. To elucidate the biologic function of PML, antipeptide antibody against PML protein was raised in rabbits. This antibody was able to detect a 90-kD PML protein and a 110-kD PML-RAR alpha fusion protein by Western blotting and a nuclear speckled pattern in all cell lines by immunofluorescent staining. In K562 and NIH/3T3 cells transfected with a PML expression plasmid, we found PML to be associated with the nuclear matrix. Our results also showed that PML is a phosphorprotein. A weak signal was detected in a Western blot containing the immunoprecipitated PML protein using the phosphotyrosine-specific monoclonal antibody. Therefore, at least one of the sites was phosphorylated by a tyrosine kinase. From our analysis of the phosphoamino acids of the PML protein by complete hydrolysis and thin layer chromatography, we concluded that both tyrosine and serine residues of PML are phosphorylated. To investigate whether expression of the PML protein is cell cycle related, HeLa cells synchronized at various phases of the cell cycle were analyzed by immunofluorescence staining and confocal microscopy for PML expression. We found that PML was expressed at a lower level in S, G2, and M phases and at a significantly higher level in G1 phase. Our study showed that PML has many similar properties compared with the tumor suppressor, eg, Rb. These findings further support the important role of PML in APL pathogenesis. PMID- 7780149 TI - Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells. AB - We previously showed that quercetin (3,3',4',5,7 pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute leukemias and is able to enhance the antiproliferative activity of cytosine arabinoside. We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2 AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of quercetin in these cells. This observation was supported by the following data. (1) Quercetin-sensitive leukemic blasts, when treated with quercetin, secrete large amounts of TGF-beta 1 in the medium and show positivity for TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of quercetin. (3) Anti-TGF beta 1 neutralizing monoclonal antibodies can prevent almost completely the growth-inhibitory activity of quercetin. The analysis of quercetin-resistant cases confirmed as well the central role of TGF-beta 1 in the growth-inhibitory activity of quercetin. In conclusion, quercetin can act as a cytostatic agent for leukemic cells by modulating the production of TGF-beta 1. PMID- 7780150 TI - The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. AB - Analysis of a growing number of chromosomal translocations in human tumors have shown that they frequently result in gene fusions encoding chimeric proteins. We have characterized the recurrent t(12;21)(p12;q22) translocation present in human B-lineage acute leukemias. This translocation fused two genes, tel and AML1, that have previously been described in chromosomal translocations specific for myeloid malignancies. These two genes therefore belong to an increasing number of human genes that are involved in a variety of hematopoietic malignant disorders and can be rearranged with numerous partners. Interestingly, in these acute leukemias, deletion of the other tel allele from the normal chromosome 12 was associated with the tel rearrangement, whereas both tel alleles were present in the chronic leukemias bearing a t(5;12) that we have tested. PMID- 7780151 TI - Prognostic value of cellular proliferation and histologic grade in follicular lymphoma. AB - The clinical usefulness of histologic grading in follicular lymphoma (FL) is controversial and is further compromised by the subjective nature and poor reproducibility of most systems in current use. Therefore, we decided to objectively evaluate the importance of cellular proliferation in FL, along with the current grading systems. We studied 106 patients with FL who were uniformly staged and aggressively treated. A proliferative index (PI) was determined quantitatively using an automated image analyzer and a new Ki-67 antibody that stains archival paraffin tissues. The cases were also subclassified according to the Berard, Rappaport, Luke-Collins, and Jaffe methods, and survival analysis was performed. Patients with a low PI (< 40%) had a significantly longer overall survival (OS) than those with a high PI (> or = 40%), but the PI did not predict failure-free survival (FFS). The mean PI correlated well with the subgroups in each of the various classifications. All four of the classification methods were predictive of OS, but only the Berard method appeared to predict FFS and suggest that a proportion of patients with FL may be curable. In multivariate analysis, histologic classification was the only independent predictor of OS (Berard method: relative risk, 3.1) and the International Prognostic Index was the only independent predictor of FFS (relative risk, 2.3). We conclude that the Berard method for grading of FL is clinically useful and, along with the International Prognostic Index, should be included in future clinical studies of FL. The measurement of cellular proliferation does not appear to add additional useful information in FL. PMID- 7780152 TI - Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: correlation with clinicobiologic findings. AB - Cytogenetic data were studied in 26 patients with de novo acute myeloid leukemia (AML) with minimal myeloid differentiation, corresponding to the M0 subtype of the French-American-British classification, in correlation with cytoimmunologic and clinical findings. Clonal abnormalities were detected in 21 cases (80.7%), 12 of which had a complex karyotype. Partial or total monosomy 5q and/or 7q was found, either as the sole aberration or in all abnormal metaphases, in 11 patients; in 8 cases, additional chromosome changes were present, including rearrangements involving 12p12-13 and 2p12-15 seen in 3 cases each. Five patients had trisomy 13 as a possible primary chromosome change; in 5 cases, nonrecurrent chromsome abnormalities were observed. Comparison of these findings with chromosome data from 42 patients with AML-M1 shows that abnormal karyotypes, complex karyotypes, unbalanced chromosome changes (-5/5q- and/or -7/7q- and +13) were observed much more frequently in AML-M0 than in AML-M1. Patients with abnormalities of chromosome 5 and/or 7 frequently showed trilineage myelodysplasia and low white blood cell count. Despite their relatively young age, complete remission was achieved in 4 of 11 patients only. Patients with +13 were elderly males with frequent professional exposure to myelotoxic agents. Unlike patients with clonal abnormalities, most AML-M0 patients with normal karyotype showed 1% to 2% peroxidase-positive blast cells at light microscopy and frequently achieved CR. It is concluded that (1) AML-M0 shows a distinct cytogenetic profile, partially recalling that of therapy-related AML, (2) different cytogenetic groups of AML-M0 can be identified showing characteristic clinicobiologic features, and (3) chromosome rearrangements may partially account for the unfavorable outcome frequently observed in these patients. PMID- 7780154 TI - Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells. AB - The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA 5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion. PMID- 7780153 TI - Heterogeneity in CBF beta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia. AB - Inv(16)(p13q22) is one of the most frequent chromosomal rearrangements found in acute myelogenous leukemia (AML), representing approximately 16% of documented karyotypic abnormalities. The inv(16) breakpoints have been cloned and shown to involve the non-DNA binding component of the AML-1 transcription factor complex termed core binding factor beta gene (CBF beta) on 16q and the smooth muscle myosin heavy chain gene (MYH11) on 16p. In this study, we analyzed 37 cases of inv(16)-containing AML and 4 cases with t(16;16)(p13;q22) for expression of the CBF beta/MYH11 chimeric message by reverse transcription-polymerase chain reaction (PCR) analysis. CBF beta/MYH11 chimeric messages were detected in 33 of 37 cases with the inv(16) and in the 4 t(16;16)-containing cases. Sequence analysis of PCR products showed extensive breakpoint heterogeneity in both CBF beta and MYH11. In addition to the previously described breakpoint in CBF beta at nucleotide (nt) 495 (amino acid 165), we have identified a second novel fusion point at nt 399 (amino acid 133) in 7% of the cases. Similarly, a unique breakpoint site was identified in MYH11 at nt 1098, as well as at three previously characterized sites at nts 994, 1201, and 1921. Of the 4 PCR-negative cases, 2 of 3 tested lacked CBF beta rearrangements by Southern blot analysis, suggesting the possible involvement of a different genomic locus in some cases with cytogenetic evidence of inv(16). To assess whether the portions of CBF-beta contained within the CBF beta/MYH11 chimeric products retain the ability to interact with their heterodimeric DNA-binding partner AML-1, we performed in vitro DNA-binding analysis. Recombinant CBF-beta polypeptides consisting of the N terminal 165 amino acids retained their ability to interact with AML-1, whereas mutants containing only the N-terminal 133 amino acids interacted with AML-1 less efficiently. These data suggest that different CBF beta/MYH11 products may vary subtly in their biologic activities. PMID- 7780155 TI - Ecotropic virus integration site-1 gene preferentially expressed in post myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. AB - We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality. PMID- 7780156 TI - Granulocyte-macrophage colony-stimulating factor increases 5-lipoxygenase gene transcription and protein expression in human neutrophils. AB - The complex process of neutrophil activation and accumulation is orchestrated by a cascade of cytokines and bioactive lipids produced at the site of inflammation. Neutrophils are a rich source of the potent inflammatory lipid leukotriene B4(LTB4). Granulocyte-macrophage colony-stimulating factor (GM-CSF) can activate neutrophils for an exponential increase in LTB4 production in response to a number of subsequent stimuli. In this report, we examined the temporal regulation, by GM-CSF, of the gene and protein expression of 5-lipoxygenase (5 LOX), a key enzyme of the LTB4 production pathway. Human neutrophils were exposed to 10 ng/mL of GM-CSF for various periods of time and 5-LOX mRNA was measured by Northern blot analysis. We observed no change in 5-LOX mRNA at early time points (0.25 to 3 hours); however, by 18 hours we observed a significant augmentation of 5-LOX-specific message (4.3 +/- 1.7-fold increase; n = 6). Nuclear transcription assays indicated that the rate of 5-LOX gene transcription was augmented threefold in neutrophils incubated with GM-CSF, whereas the half-life of the message was not markedly changed. Parallel experiments indicated that the levels of 5-LOX protein were also increased by GM-CSF. The augmentation was observed within 30 minutes after stimulation and was maximal (5.23 +/- 2.6; n = 4) at 18 hours. Incubation of GM-CSF-stimulated neutrophils with protein synthesis inhibitors resulted in a time-dependent impairment of their ability to produce LTB4, with no inhibition seen during the first hours, a 75% decrease seen by 12 hours, and greater than 95% inhibition seen at 18 hours. Collectively, our data imply that GM-CSF can regulate LTB4 production by two distinct mechanisms: a short-term increase that is not related to increased 5-LOX mRNA expression and is independent of protein synthesis, and a sustained increase in LTB4 production that is associated with the transcriptional activation of the 5-LOX gene, increase in 5-LOX mRNA levels, and dependence on protein synthesis. Such transcriptional modulation of 5-LOX enzyme expression may provide new approaches for therapeutic intervention in protracted inflammatory conditions. PMID- 7780157 TI - Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: its underlying mechanism in comparison with interleukin-4. AB - Both interleukin-10 (IL-10) and IL-4 inhibited the prostanoid synthesis of lipopolysaccharide (LPS)-stimulated human monocytes, and their inhibition was shown to be based on a common mechanism to suppress the gene expression of inducible cyclooxygenase (COX). COX has been shown to exist in at least two distinct isoforms, designated COX-1 and COX-2, and their gene expressions exhibit different profiles. At both the protein and mRNA levels, the expression of COX-1 was constitutive and was not modulated by treatments with LPS, IL-10, or IL-4. In contrast, the expression of COX-2 was observed only after stimulation with LPS. IL-10 and IL-4 significantly inhibited LPS-induced COX-2 expression. Kinetic studies showed that they inhibited COX-2 mRNA expression within 1 hour after stimulation and that maximal inhibition was consistently observed at 5 hours. Moreover, the addition of cycloheximide (CHX) to LPS-stimulated monocytes resulted in a superinduction of COX-2 mRNA, whereas CHX almost abrogated the abilities of IL-10 and IL-4 to inhibit this gene expression. Experiments with actinomycin D showed that both cytokines accelerated the degradation of COX-2 mRNA. Furthermore, nuclear run-on experiments showed that both cytokines modestly inhibited LPS-induced COX-2 gene transcription. Thus, both cytokines seemed to regulate the COX-related pathway in a similar manner, although their receptor systems did not show any structural similarities. Considering recent findings showing that the drugs that exhibit a selective effect on COX-2 may be more preferable in inflammatory conditions, such biologic activities of IL-10 and IL-4 described above may offer useful tools in controlling inflammatory disorders in the future. PMID- 7780158 TI - Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. AB - A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non-Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products. PMID- 7780159 TI - Association of gastroesophageal reflux with obstructive lung disease in children after allogeneic bone marrow transplantation. PMID- 7780160 TI - Transient disappearance of sickle hemoglobin after transfusion. PMID- 7780161 TI - Glucose-6-phosphate dehydrogenase (G6PD) mutations associated with F8C/G6PD haplotypes in Chinese. PMID- 7780162 TI - All-trans retinoic acid for advanced multiple myeloma. PMID- 7780163 TI - Levels of activated factor VII in patients with disseminated intravascular coagulation. PMID- 7780164 TI - Spinocerebellar ataxia 1 (SCA1) in the Japanese: analysis of CAG trinucleitide repeat expansion and instability of the repeat for paternal transmission. AB - SCA1 is caused by expansion of an unstable CAG triplet repeat in a novel gene located on the short arm of chromosome 6. In 126 Japanese individuals from 12 pedigrees with SCA1, studies were done to determine if they carried this mutant gene. All the affected and pre-symptomatic individuals, determined by haplotype segregation analyses, carried an abnormally expanded allele with the range of 39 63 repeat units. This repeat size inversely correlated with the age at onset. However, contrary to reported results, size of the repeat did not correlate with gender of the transmitting parent. Therefore, the CAG triplet repeat instability on paternal transmission is not likely to be fundamental to SCA1. PMID- 7780165 TI - Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization. PMID- 7780166 TI - A novel sequence polymorphism in exon 8 of the human vitamin D-binding protein (GC) gene in an African population. AB - A novel sequence polymorphism due to a T to C transition at the third nucleotide of the codon for Cys283 of the vitamin D-binding protein (GC) gene assigned to chromosome 4q13-4q21.1 was revealed by sequence analysis. Population studies by single strand conformation polymorphism (SSCP) analysis showed this GC-283.3 site was polymorphic in a Black African population but monomorphic in a European population. PMID- 7780167 TI - [Lifestyles and renal damage--association of smoking, drinking and physical activity with subsequent proteinuria]. AB - To examine the role of lifestyles in the subsequent development of renal damage, the association of smoking, drinking and physical activity with subsequent proteinuria was investigated utilizing a longitudinal study. The subjects were 7,701 males aged 20-84 years, who participated in health examinations at Aichi Prefectural Center of Health Care, Nagoya, Japan, both in 1989-1990 and 1992 1993, and who showed no proteinuria at the first examination. Lifestyles at the first examination were compared between 140 men with, and 7,561 men without, newly developed proteinuria at the second examination. Age-adjusted odds ratios (ORs) of lifestyle factors for proteinuria were computed, and further the ORs were adjusted for age, systolic blood pressure, fasting plasma glucose level and other covariates obtained using multiple logistic regression analysis. Major significant findings which emerged from the present study were as follows. (a) The greater the consumption of alcohol per day, the higher the risk of subsequent proteinuria (trend p = 0.003). Heavy drinkers who consumed more than 58 g of alcohol per day experienced an increased risk (OR relative to non-drinker: 2.52). (b) Those who exercised less than once a week, and those who avoided walking even a short distance were at an increased risk (OR: 1.46, 1.55, respectively). Heavy drinking and low physical activity were found to be significantly associated with an increased risk of subsequent proteinuria even after adjusting for the covariates. An increasing risk of subsequent proteinuria with number of cigarette smoked per day was observed by univariate and multivariate analysis but without statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780168 TI - [Feasibility of "well-aging facility" of "well-aging community promotion program"]. AB - The government "Well-Aging Community Promotion Program" (WAC) defines a "Well Aging Facility" (WAF) consisting of a gymnasium for the elderly, an education center for the elderly, a service-center for handicapped elderly and their families, and a fee-for-service nursing home, and incorporated funding provisions for WAF. Because of economic reasons, with the exception of fee-for-service nursing home, there is only one WAF at present. An economic-feasibility study of WAF was conducted based on regional analysis of existing public facilities and the needs of the elderly, and proposals for promoting WAF and WAC were made. The results are as follows: 1. In large and middle-size cities, many types of public facilities exist within walking distance, but the number per capita of elderly is low. In small-size cities and towns the number per capita of elderly is high, but are rarely within walking distance. 2. Rather than investment in facilities, the role of private business in WAC can be described as investment in services such as management-services for public facilities and transportation among facilities. 3. As for economic feasibility of WAF, in large and middle-size cities the education-center is viable, but for the gymnasium facility it would be based on utilization of facilities not only for elderly but multi-generational. The feasibility for the service-center will be high in large cities but low in middle size cities. 4. For small-size cities and towns, the management of the gymnasium, and the education-center will be feasible, but the service-center will be difficult. 5. To promote WAC in small-size cities and towns, the following will be needed. a. The development of transportation systems between homes and facilities. b. The promotion of multi-purpose use of facilities beyond the established purpose of each WAC public facility. c. The establishment of new multi-sectional management entities by both the public and private sectors to manage existing public facilities. d. Development of financial support program by the government for upgrading and remodeling of existing facilities to function as an alternative of the WAF. PMID- 7780169 TI - [Relationship between daily high temperature and mortality in Kyushu, Japan]. AB - We analyzed the relationship between daily high temperature and mortality in Kyushu, Japan, 1972-1990. Mortality rate was obtained by dividing the number of deaths in a certain daily high temperature category by person-days in the same category. The results were as follows: (1) With daily high temperature on the x axis and mortality rate on the y-axis, the relationship between the two variables appeared to be V-shaped. The minimum mortality rate was observed at the 28 degrees C-33 degrees C level. (2) Among all deaths at 33+ degrees C level, the proportion of deaths from "excessive heat" never exceeded 0.4%. This suggested that heat stroke is not a major contributor to the V-shape formation. (3) The V shape was observed even in 1990, suggesting that the rapid spread of air conditioners did not alter the relationship between daily high temperature and mortality rate. (4) For the 0-4 years age group, mortality was not temperature dependent. However, the 5-14 years age group showed high mortality rates at 33+ degrees C. This may be attributed to outdoor activities during summer. After 30 years of age, the overall mortality rates rose with age, with greater increases at lower ambient temperature levels. As a result, the 65+ years age group had the greatest temperature dependence. (5) Deaths from respiratory diseases, circulatory diseases, and senility were highly temperature dependent, whereas death from cancer was not temperature dependent. Deaths from digestive diseases, infectious diseases, and accidents showed moderate temperature dependence. PMID- 7780170 TI - [AIDS/HIV related knowledge, attitude and behavior of acupuncture therapists in Aichi Prefecture]. AB - To promote AIDS prevention measures in Japan, the actual state of knowledge, attitudes and behaviors (KAB) of workers at risk for HIV infection requires clarification. In the present study, acupuncture therapists in Aichi Prefecture were evaluated for level of their KAB. By using a self-administered questionnaire, the KAB condition of 500 acupuncture therapists was surveyed from September-November in 1993. Responses from 494 (98.8%) were available for analysis. Results showed that knowledge level on general issues regarding HIV epidemics was good. The main sources for information on AIDS/HIV were TV, general lectures, public reports and magazines. More than 80% of acupuncture therapists sterilize their needles by autoclave or boiling and 60% of them use disposable needles. Furthermore, 97% of the therapists reported utilizing one or the other of these methods. More than a half of them have participated in AIDS education programs. While about 30% of them responded that they are able to accept HIV carriers as clients, 20% of them expressed negative responses. There appears to be a discrepancy between their level of knowledge of HIV transmission routes and their practical attitude towards clients with AIDS and/or HIV carriers. A more appropriate education program based on behavioral science is desirable to lessen discrepancy distance between general knowledge and preferable behavior regarding AIDS/HIV. PMID- 7780171 TI - [Sociomedical concerns of physically handicapped persons using wheelchairs and living in the community--a preliminary study on patients suffering from spinal cord injuries]. PMID- 7780172 TI - Transient and continuous expression of NADPH diaphorase in different neuronal populations of developing rat spinal cord. AB - Nitric oxide is a novel intercellular messenger whose role in neuronal development is not yet known. As a first step toward elucidating its developmental function, we examined the pattern of NADPH diaphorase histochemical staining, an indicator of the presence of nitric oxide synthase, in the rat spinal cord at pre and postnatal ages. Some types of neurons expressed diaphorase activity transiently during development. For example, a subset of somatic motor neurons, located in the ventrolateral corner of a few caudal segments of the cervical spinal cord, were diaphorase-positive beginning on E15, but gradually became diaphorase-negative by birth. In contrast, other spinal neurons expressed diaphorase activity continuously from development into adulthood. Preganglionic autonomic motor neurons became diaphorase-positive early in their development, as they were migrating toward their adult positions. Other spinal neurons, such as those in superficial dorsal horn, first expressed diaphorase relatively late in their development, after reaching their final location. The transient expression in some cell types, as well as the early expression in others, suggest that nitric oxide may have an important role(s) during development, which may differ from its functions in the adult nervous system. PMID- 7780173 TI - Collagen fibrillogenesis in situ: fibril segments undergo post-depositional modifications resulting in linear and lateral growth during matrix development. AB - Elucidating how collagen fibril growth is regulated is important in determining how tissues are assembled. Fibrils are deposited as segments. The growth of these segments is an important determinant of tissue architecture, stability, and mechanical attributes. Fibril segments were isolated from developing tendons and their structure characterized. The post-depositional changes leading to linear and lateral growth of fibrils also were examined. Segments extracted from 14-day chicken embryo tendons had a mean length of 29 microns. The segments were asymmetric, having a short and a long tapered end. Most of the segments were centrosymmetric with respect to molecular packing. Segments extracted from 12- to 16-day tendons had the same structure, but mean segment length increased incrementally due to the addition of an increasingly large population of longer segments. At 17 days of development there was a precipitous increase in segment length. The morphological data indicate that the increase in length was the result of lateral associations among adjacent segments. Analysis demonstrated that this fibril growth was associated with a significant decrease in fibril associated decorin. Using immunoelectron microscopy, decorin was seen to decrease significantly at 18 days of development. When decorin content was biochemically determined, a decrease also was observed. Decorin mRNA also decreased relative to fibrillar collagen mRNA during the same period. These data support the hypothesis that a decrease in fibril-associated decorin is necessary for fibril growth associated with tissue maturation. Growth through post-depositional fusion allows for appositional and intercalary growth and would be essential for normal development, growth, and repair. PMID- 7780174 TI - MyoD protein accumulates in satellite cells and is neurally regulated in regenerating myotubes and skeletal muscle fibers. AB - MyoD belongs to a family of helix-loop-helix proteins that control myogenic differentiation. Transfection of various non-myogenic cell lines with MyoD transforms them into myogenic cells. In normal embryonic development MyoD is upregulated at the time when the hypaxial musculature begins to form, but its role in the function of adult muscle remains to be elucidated. In this study we examined the cellular locations of MyoD protein in normal and abnormal muscles to see whether the presence of MyoD protein is correlated with a particular cellular behaviour and to assess the usefulness of MyoD as a marker for satellite cells. Adult rats were anaesthetised and their tibialis anterior or soleus muscles either denervated, tenotomised, freeze lesioned, lesioned and denervated, or lesioned and tenotomised. At various intervals after the operations the rats were killed and their muscles removed, snap frozen, and sectioned with a cryostat along with muscles from unoperated neonatal and adult rats. The sections were processed for immunohistochemistry using a rabbit affinity-purified antibody to recombinant MyoD. MyoD proved to be an excellent marker for active satellite cells; satellite cells in neonatal and regenerating muscles contained high levels of MyoD protein. MyoD positive cells were not observed in the muscles of old adults, in which the satellite cells are fully quiescent. MyoD immunoreactivity was rapidly lost from satellite cell nuclei after they fused into myotubes and was not detected in either sub-synaptic or non-synaptic nuclei of mature fibers. Denervation, and to a lesser extent tenotomy, of lesioned muscles induced expression of MyoD in myotubal nuclei. Denervation of normal muscles also upregulated MyoD in muscle fiber nuclei, an effect which was maximal after 3 days. We conclude that MyoD protein is neurally regulated in both myotubes and muscle fibers. PMID- 7780175 TI - Cyclopamine, a steroidal alkaloid, disrupts development of cranial neural crest cells in Xenopus. AB - Cyclopamine is a steroidal alkaloid which causes limb and craniofacial defects in many vertebrate species. We have used Xenopus laevis as a model system to characterize the defects caused by cyclopamine at the cellular level. The most dramatic consequence of cyclopamine treatment in the Xenopus embryo is a defect in formation of craniofacial cartilage. Much of this cartilage is absent in treated animals. As in avian and mammalian species, Xenopus craniofacial cartilage is derived primarily from cells of the cranial neural crest. Grafting experiments show that development of the cartilaginous derivatives of the cranial neural crest is impaired after cyclopamine treatment, and this is at least partially due to a direct effect on presumptive crest cells. A culture system was used to determine the cellular response to the drug. Cyclopamine did not block the initial emigration of cells from a neural plate explant. However, cell death is seen in treated cultures after 4 days. Trunk neural crest cells and transformed cell lines are resistant to cyclopamine. We therefore conclude that cyclopamine specifically causes death of cranial neural crest cells and that lethality is likely to account for the teratogenic effects of this compound. PMID- 7780176 TI - Retinoic acid-induced cell death in the wound epidermis of regenerating zebrafish fins. AB - Previous work has shown that treatment with retinoic acid (RA) can induce malformations in regenerating pectoral and caudal fins. RA-treated regenerates are narrower than unamputated and regenerated control fins because of a decrease in the distance between rays, and either partial or total fusion of some of them. In order to tackle the issue of how RA induces its teratogenic effects on regenerating fins, and which cell types may be specifically affected by RA, we have examined the cellular changes occurring in early regenerates following treatment with retinoids. The work presented here shows for the first time that RA induces significant apoptosis in the wound epidermis, but not in the mesenchyme, of a regenerating appendage, besides inhibiting blastema development as reported in other species. We also show that RA does not retard regeneration by inhibiting accumulation of blastemal cells, but probably by impairing their ability to migrate distal to the amputation plane. This effect is rapidly reversed by discontinuing the treatment, and within 24 hr of removing the drug, blastema development is well advanced. By this time the teratogenic effects induced by RA are already apparent. A correlation between the length of the apical ectodermal ridge (AER) and the number of digits formed has been demonstrated in developing limb buds. We therefore suggest that RA-induced patterning abnormalities in regenerating fins are the consequence of a reduction in the size of the wound epidermis, due to increased cell death, which would affect patterning of the underlying mesenchyme. PMID- 7780177 TI - Basal lamina development in chicken muscle spindles. AB - The development of basal laminas was examined in immunohistochemical sections of chicken leg muscle spindles from embryonic day (E) 13 to 8 weeks postnatal. Fragments of basal laminas as seen with immunostaining for isoforms of laminin were already observed in E6 muscles. When clusters of intrafusal myotubes were first recognized at E13-14, they were surrounded by basal laminas which were incomplete both in terms of coverage and molecular composition. More mature basal lamina tubes individually enclosed young myofibers at E18. After afferents made contact with myotubes, synaptic portions of basal laminas at myosensory junctions reacted strongly with antibodies against s-laminin and chondroitin sulfate proteoglycan, while extrasynaptic portions were negative or reacted only weakly. At synaptic basal laminas of neuromuscular junctions heparin sulfate proteoglycan and s-laminin became prominent after E16. Contrary to the early presence of basal lamina proteins around intrafusal fibers, initial deposition of basal lamina proteins in the outer spindle capsule was not recognized until E17-18, and significant amounts were not detected until postnatal week 1. Unlike intrafusal basal laminas, capsular basal laminas developed no distinct specialized regions; however, molecular compositions of intrafusal and capsular basal laminas were similar. PMID- 7780178 TI - Clusterin expression within skin correlates with hair growth. AB - Clusterin/TRPM-2 is a sulfated glycoprotein that is expressed in many tissues. Independently cloned and isolated by several laboratories, it bears many names, and has been shown to be involved in many processes. These include cell-cell adhesion and aggregation, inhibition of complement cytolysis, programmed cell death and apoptosis, tissue remodeling, and terminal differentiation. The hair follicle undergoes cycles of growth, regression, and rest, which involve both tissue remodeling and programmed cell death. To identify whether clusterin expression is involved in hair growth and cycling, we studied the expression of clusterin throughout the hair cycle. We demonstrate that clusterin is expressed during the growth phase of the hair cycle. We found no correlation between clusterin expression and the apoptotic regression of the hair follicle. Using immunohistochemistry we localized clusterin to the inner root sheath of the follicle. This suggests that clusterin might be involved in the morphogenesis and differentiation of the hair follicle. We propose that clusterin has a role in the maintenance of the layered structure of the hair follicle, and in the interactions between the inner root sheath and both the outer root sheath and the PMID- 7780179 TI - Expression of two new protein isoforms of the neurofibromatosis type 1 gene product, neurofibromin, in muscle tissues. AB - The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein, termed neurofibromin, which is expressed predominantly in neurons, Schwann cells, oligodendrocytes, and leukocytes. There are at least three isoforms of neurofibromin produced by the alternative use of exons 23a and 48a. Previously we described the identification of an NF1 mRNA isoform containing an additional 54 nucleotides from exon 48a (type 3 NF1) in human skeletal, cardiac and smooth muscle tissues by reverse-transcribed (RT)-PCR. To extend our initial observations, we have produced high titer chicken IgY antibodies which specifically recognize this muscle-specific neurofibromin isoform. An NF1 cDNA was generated containing human exon 48a sequences and expressed as a fusion protein in bacteria. The muscle-specific neurofibromin antibodies detected this exon 48a fusion protein by Western immunoblotting. Immunoprecipitation using these type 3 neurofibromin antibodies also specifically detected a 250 kDa protein in human and rat muscle tissues. Type 3 neurofibromin was found in rat heart and muscle, but not in liver brain, kidney or spleen with levels of expression declining after postnatal day 7. Expression of total NF1 RNA during rat embryonic development was detected at high levels in E15 heart, tongue, and limb bud. In addition, using type 2 neurofibromin-specific antibodies, the existence of a fourth isoform of neurofibromin (type 4 neurofibromin) containing both exon 23a and 48a sequences was demonstrated in rat heart muscle tissues. The identification of two muscle-specific isoforms of neurofibromin expands our definition of this important tumor suppressor protein and suggests additional roles for neurofibromin in muscle development and differentiation. PMID- 7780180 TI - Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo. AB - We have analysed the endogenous retinoids present in whole mouse embryos from day 9 to day 14 of development and in individual components of the embryo at two stages, day 10.5 and day 13, by HPLC. We can only detect two retinoids, all-trans RA (tRA) and all-trans-retinol (t-retinol), and t-retinol is 5-10-fold in excess over tRA. We cannot detect 9-cis-RA or any didehydroretinoids; thus mammalian embryos seem to differ in their retinoid content from other embryos such as chick, Xenopus, and fish. The levels of tRA do not change significantly over the 6 days of development analysed, whereas t-retinol rises sharply as the liver develops. Within the embryo, tRA is present at high levels in the developing spinal cord and at very low levels in the forebrain; indeed there is a gradient of endogenous tRA from the forebrain to the spinal cord. Other parts of the embryo had intermediate levels of tRA. When a teratogenic dose of RA was administered to day 10.5 embryos, the levels of tRA present in individual tissues of the embryo rose dramatically--from 175-fold to 1,400-fold--and the levels rose in all tissues not in any exclusive areas. We then determined which areas of the embryo were malformed by such a teratogenic dose. The lower jaw, palate, vertebrae, tail, and limbs were consistently abnormal, and since these areas received a dose of tRA no higher than any other it was concluded that cell specific factors must determine the teratogenic response of these tissues. We then considered whether cellular retinoic acid-binding protein I or II (CRABP I or II) played any role in this response by determining their relative levels in each of the tissues analysed. There was no correlation between the presence of CRABP I and II and the distribution of administered RA. Neither was there a clear correlation in detail between the presence of CRABP I and II and the sites of teratogenesis. We therefore conclude that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA. PMID- 7780181 TI - Tracking genetically engineered microorganisms in nature. AB - The past year has seen the continued development of methods for tracking genetically engineered microorganisms in nature, with an emphasis on increased sensitivity, specificity and quantitative ability. In addition, novel methods have been developed for tagging bacteria targeted for environmental release. Nevertheless, the limited number of field trials published to date have primarily relied on conventional monitoring methods, despite the availability of better and theoretically safer methods. PMID- 7780182 TI - Further development of recombinant baculovirus insecticides. AB - On the basis of recent laboratory and field experiments, recombinant baculoviruses expressing insect-specific neurotoxin genes show an increased speed of insect killing compared with natural baculoviruses. They can also induce symptoms similar to those induced by chemical insecticides and have the potential for widespread use in agriculture. Current studies of the ecology and molecular biology of baculoviruses should further improve efficacy and better define safety. PMID- 7780183 TI - Environmental biotechnology. PMID- 7780184 TI - Renal function conscious one kidney-one clip hypertensive rats. Effect of indomethacin. AB - These experiments have analyzed: a) Blood pressure (BP) and renal function in one kidney-one clip rats two weeks after clipping; b) The effect of cycloxygenase (CO) inhibition on BP and renal function regulation during the hypertensive period. Using the unanaesthetized, unrestrained and chronically instrumented animal, three groups of rats were studied: Sham, Clip 0.31 mm lumen and Clip 0.29 mm lumen. The animals were examined before (Control period) and during the infusion of indomethacin (IND, 5 mg/kg via aortic cannula, n = 11 for each group) or the buffer vehicle solution (BUF, n = 7 for each group). Effective inhibition of CO by IND was confirmed using radioimmunoassay of prostaglandin E2 (PGE2) in urine. Control BP (mmHg, mean +/- SE) differed significantly among the groups (p < 0.001): Sham, 114 +/- 3; Clip 0.31, 135 +/- 2; Clip 0.29, 154 +/- 4 and did not change by IND infusion. Along with the BP, Control Glomerular Filtration Rate and Renal Plasma Flow did not change by IND infusion, which suggests that CO eicosanoids, particularly PGG2, contribute little to basal renal hemodynamics in sham and hypertensive rats. Sodium excretion was lower in the Control period of Clip 0.29 rats (p < 0.01). A significant natriuretic effect observed in this Clip 0.29 group by the infusion of IND suggests the contribution of an AA related metabolite in renal handling of sodium in more severe renovascular hypertension. PMID- 7780186 TI - [Argentine Society of Experimental Pharmacology, XXV annual meeting. Mar del Plata, 1993. Abstracts]. PMID- 7780185 TI - [Identification of antibodies against cardiac muscarinic cholinergic receptors (CMCR) in blood from chagasic patients. Pathogenic implications]. PMID- 7780187 TI - 1-Deoxymannojirimycin is a non-competitive inhibitor of mannosidase II. PMID- 7780188 TI - Expertise in glycobiology--the invisible category. PMID- 7780189 TI - Structure and function of laminin 1 glycans; glycan profiling. PMID- 7780190 TI - Cell surface components of Leishmania: identification of a novel parasite lectin? AB - Protozoan parasites of the genus Leishmania have a glycoconjugate surface coat (the glycocalyx) that acts as the interface between the parasite and its external environment. The principal components of the glycocalyx, the lipophosphoglycans and the glycoinositolphospholipids, have a variety of functions that facilitate parasite survival in both the extracellular and the intracellular stages of the life cycle. Recently, a novel hydrophilic Leishmania protein, the Gene B protein, has been identified on the surface of infective parasite stages. Attachment to the surface appears to be by association between a region of repeated amino acids in this molecule and components of the glycocalyx. As a consequence, the Gene B protein is exposed on the parasite surface while other peptides are buried beneath the glycocalyx. The putative functions of this unusual molecule are discussed. PMID- 7780191 TI - Tritium labelling of amino sugars at C-2 by alkaline epimerization in tritiated water. AB - N-Acetyl-D-[2-3H]glucosamine was synthesized from N-acetyl-D-mannosamine by alkaline 2-epimerization in pyridine containing 3H2O and nickelous acetate. The reaction involves reversible formation of an enol intermediate and therefore also resulted in incorporation of tritium into N-acetylmannosamine. After completed reaction, the two N-acetylhexosamines were separated from other radioactive products and Morgan-Elson chromogens by chromatography on a column of Sephadex G 10, which was eluted with 10% ethanol, and were then separated from each other by chromatography on Sephadex G-15 in 0.27 M sodium borate (pH 7.8). The location of the incorporated tritium was established by treatment of the N-acetylhexosamines with borate under the conditions of the Morgan-Elson reaction, which converts the sugars to Kuhn's chromogen I with concomitant loss of the C-2 hydrogen. As expected, this treatment resulted in the formation of 3H2O, indicating that the tritium was located at C-2. [2-3H]Glucosamine was prepared by acid hydrolysis of the labelled N-acetylglucosamine and was converted to [2-3H]glucosamine 6 phosphate by incubation with hexokinase and ATP. The sugar phosphate was used as a substrate for glucosamine 6-phosphate deaminase (isomerase, EC 5.3.1.10) in a simple 3H2O release assay. PMID- 7780192 TI - Characterization of the glycosylation of a human IgM produced by a human-mouse hybridoma. AB - We analysed the oligosaccharides of a human IgM produced by a human-human-mouse hybridoma at each of its five conserved heavy chain glycosylation sites. Consistent with previous reports, this IgM possesses sialylated oligosaccharides at Asn171, Asn332 and Asn395, and high-mannose-type oligosaccharides at Asn402. In contrast to previous reports for human IgMs, we find that Asn563 is not occupied by oligosaccharide on perhaps 25% of IgM heavy chains, while occupied Asn563 sites contain both high-mannose-type and sialylated oligosaccharides. These latter results are consistent with the glycosylation at Asn563 previously reported for the mouse MOPC 104E IgM. We demonstrate that both the human hybridoma IgM and the mouse MOPC 104E IgM are mixtures of pentamers and hexamers, raising the possibility that the unique findings concerning the glycosylation at Asn563 in this study and the previous study of the MOPC 104E IgM could be related, at least in part, to the different packing requirements of the hexameric geometry and the accessibility of oligosaccharides in the hexameric geometry for processing to complex type. In addition, we used high-pH anion-exchange (HPAE) chromatography, neutral anion-exchange chromatography, fluorophore-assisted carbohydrate electrophoresis and Western blots to compare the oligosaccharide compositions of the human hybridoma IgM, pooled human serum IgM and two mouse monoclonal IgMs (MOPC 104E and TEPC 183). Of note is the presence of N glycolylneuraminic acid (NeuGc) and N-acetylneuraminic acid (NeuAc) at a 2:1 ratio in the oligosaccharides of the human hybridoma IgM. The presence of both NeuGc and NeuAc complicates the interpretation of HPAE chromatographs. PMID- 7780193 TI - Localization of neutral and acidic glycosphingolipids in rat lens. AB - Rat lens was found to contain several neutral and acidic glycosphingolipids in lens epithelia, cortex and nucleus, and showed developmental changes in their content and localization. TLC-immunostaining of gangliosides revealed the enrichment of some ganglio-series gangliosides (GM3, GM1, GD3 and GD1b) in lens epithelia and the presence of GM3 and GD3 in the lens nucleus. Immunohistochemical studies confirmed the distribution of GM3 and GM1 in anterior lens epithelial cells and the cortex, with expression decreasing toward the lens nucleus. Immunoreaction to GD3 was more intense in the lens nucleus than in epithelial cells. In contrast, the expression of neolacto-series glycosphingolipids was restricted to the lens nucleus. In order to investigate the pathological changes of glycosphingolipids in cataract, galactose-induced cataractous lenses were examined. However, no significant changes were observed in the content and composition of glycosphingolipids. In addition, Lewisx epitopes found in human cataractous lenses were not detected in the cataractous lenses of galactosaemic rats and hereditary cataractous Emory mice. PMID- 7780194 TI - The saccharides of the MUC 1 mucin-type glycoprotein, epitectin, produced by H.Ep.2 cells in the presence of aryl-N-acetyl-alpha-galactosaminides. AB - The treatment of H.Ep.2 cells with 4 mM aryl-N-acetyl-alpha-galactosaminide, an inhibitor of the elongation of O-linked saccharides of glycoproteins, resulted in a 70-80% decrease in the incorporation of [3H]glucosamine into epitectin (a MUC 1 mucin-type glycoprotein). Gel electrophoresis of the partially glycosylated epitectin immunoprecipitated from the extracts of treated cells showed two bands of apparent mol. wts 420 and 460 kDa on SDS-PAGE, compared to bands of 350 and 390 kDa for the native epitectin. Analysis of the saccharides released by beta elimination from the partially glycosylated epitectin showed the presence of substantial levels of beta 1-->3 galactosylated and sialylated saccharides. The data indicate that the inhibition of elongation of Ser/Thr-linked N-acetyl galactosamine in epitectin by aryl-N-acetyl-alpha-galactosaminides is only partial. PMID- 7780195 TI - Effect of metal ions on sucrose synthase from rice grains--a study on enzyme inhibition and enzyme topography. AB - The inhibition of the plant glycosyltransferase sucrose synthase from rice grains by free metal ions was studied. Decreasing sucrose synthase activities in the order of metal ions (Cu2+ >> Zn2+ > or = Ni2+ > Fe2+; 15.4% residual activity with 30 microM Cu2+) as well as inhibition by diethyl pyrocarbonate (27% residual activity at pH 7.2 and 43 microM diethyl pyrocarbonate) provided evidence that histidyl residues are important for sucrose synthase activity. Chelated metal ions, due to the geometric restriction of the reagent, gave a less pronounced inhibitory effect (11.7% residual activity with 100 microM Cu2+), but suggested that surface-accessible histidine residues are probably involved. Inhibition of sucrose synthase could always be prevented by metal ion scavengers [ethyl enediaminetetra-acetic acid (EDTA), dithiothreitol (DTT), mercaptoethanol, reduced glutathione, imidazole and histidine]. Sucrose synthase inhibited by free and chelated Cu2+, respectively, could be partly (60%) reactivated by EDTA. These results led to a topographical analysis of histidines on the surface of the homotetrameric protein by immobilized metal ion chromatography (IMAC). From the order by which sucrose synthase was bound to immobilized chelated metal ions in the presence of 1 mM imidazole (Cu2+ > Ni2+ > Zn2+ = Co2+), it could be concluded that the enzyme has at least 5-7 surface-accessible histidines. Sucrose synthase could not be eluted from a Cu2+ column by an increasing imidazole gradient. These results are of particular interest for the further purification of sucrose synthase(s), as well as for the evaluation of cloning and expression strategies using polyhistidine tails. PMID- 7780196 TI - High alpha-2,6-sialylation of N-acetyllactosamine sequences in ras-transformed rat fibroblasts correlates with high invasive potential. AB - Through cloning experiments with the FRras EJ4 cell line, previously described to exhibit a Sambucus nigra agglutinin (SNA)+ phenotype, three clones with a SNA- phenotype were isolated. All the selected SNA+ and SNA- clones expressed the ras oncoprotein and cloned in soft agar with the same efficiency. We were interested in studying the adhesion and invasion properties of the FRras cells presenting a SNA + or - phenotype. They were first compared in their biochemical properties and we found that FRras SNA- were characterized by a low alpha-2,6-sialylation of their cell surface glycoproteins and a low beta-galactoside alpha-2,6 sialytransferase activity. Using in vitro invasion assays, FRras cells exhibiting a low alpha-2,6-sialylation on their surface were found to have a low invasive potential compared to their counterpart SNA+. FRras SNA-clones exhibit a different morphology from that of FRras SNA+ clones. Moreover, homotypic aggregation assays indicated that FRras SNA- were more cohesive with each other and adhesion assays showed that they were more adhesive to fibronectin. PMID- 7780197 TI - The critical glycosylation site of human transferrin receptor contains a high mannose oligosaccharide. AB - The human transferrin receptor (TfR) contains three N-linked oligosaccharides and glycosylation is required for the proper folding and function of the molecule. Earlier studies demonstrated that the oligosaccharide at Asn-727 is vital for the production of fully active TfR. The oligosaccharide(s) present at this site have been analysed using a combination of site-directed mutagenesis and chemical analysis. Wild-type TfR and mutants containing only the Asn-727 site or missing all three sites were transfected into mouse 3T3 cells and receptors were analysed by endo-N-acetylglucosaminidase H (Endo-H) digestion, SDS-PAGE and immunoblotting. These studies suggested that the Asn-727 site contains high mannose or Endo-H-sensitive hybrid oligosaccharides. Glycosylation of Asn-727 found in the TfR purified from human placentae was analysed by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and mass spectrometry following tryptic digestion, peptide purification via reverse-phase high-performance liquid chromatography (RP-HPLC) and peptide sequencing. HPAE-PAD showed the presence of a series of high-mannose oligosaccharides. Mass spectrometry confirmed these observations, but also showed the presence of an 80 Da anionic moiety on a fraction of the oligosaccharides. PMID- 7780198 TI - Rhizobial lipo-oligosaccharide nodulation factors: multidimensional chromatographic analysis of symbiotic signals involved in the development of legume root nodules. AB - Nod factors are a group of biologically active oligosaccharide signals that are secreted by symbiotically competent bacteria of the family Rhizobiaceae. Their biosynthesis is determined by rhizobial nodulation (nod) genes, and is specifically induced in response to flavonoids secreted from the roots of host leguminous plants. The biological activity of Nod factors on these host legumes dramatically mimics the early developmental symptoms of the Rhizobium-legume symbiosis including, amongst other effects, root hair deformations and nodule initiation. Structurally, all Nod factors are short oligomers of beta-1,4-linked N-acetylglucosamine residues [usually degree of polymerization (dp) 4 or 5] that are N-acylated on the distal glucosamine. This common 'core' structure may be modified by a number of species-specific substituents on the distal or reducing sugars. These modifications are governed by rhizobial host specificity nod genes. The biological activity of purified Nod factors mirrors this host specificity, indicating that the symbiotic host range of individual Rhizobium species is, at least partially, determined by the variety of Nod factors they are able to produce. Here we describe techniques that are universally applicable to the extraction, chromatographic separation and identification of Nod factors. We have applied these techniques to Nod factors from the broad-host-range species Rhizobium fredii USDA257 and Rhizobium spp. NGR234, and the more narrow-host range Bradyrhizobium japonicum USDA110, and have identified a group of novel, relatively hydrophilic Nod factors from the NGR234 species that may have implications for Nod factor biosynthesis. PMID- 7780199 TI - Treatment with the alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine reduces the detection of LFA-1 (CD18/CD11a) by monoclonal antibodies. AB - The antiviral clinical candidate 6-O-butanoyl castanospermine (MDL 28,574), an alpha-glucosidase 1 inhibitor, was examined for its effect on elementary parameters of immune function. It did not affect the mitogenic response of uninfected human mononuclear leukocytes or the detection of a range of cell surface markers, with the exception of the integrin LFA-1 (CD18/CD11a), which was reduced, after cell growth in vitro. The detection of LFA-1 was also reduced on both human and murine cells after oral administration of the compound to xenochimaeric or normal mice, respectively. Altered LFA-1 expression or function may contribute to reduced cell adhesion and the observed reduction in the in vitro allogeneic response by uninfected cells, as well as the previously described prevention of cell conjugate and HIV-induced syncytium formation. PMID- 7780200 TI - The effect of oral treatment with 6-O-butanoyl castanospermine (MDL 28,574) in the murine zosteriform model of HSV-1 infection. AB - Oral treatment of mice, cutaneously infected with herpes simplex virus type 1 (HSV-1) (strain SC16), with the alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28,574) produced a significant delay in lesion development and reduced the amount of virus recovered from the brain. Virus load in the brains of mice, whose treatment started 2 days prior to infection, was reduced approximately 100-fold when compared to untreated controls. Treatment initiated at the time of infection, while less effective than pre-treatment, nevertheless reduced virus recovery from the brain by 10-fold. Consistent with its antiviral activity, orally administered MDL 28,574 was rapidly incorporated by brain tissue and mice fed with compound over extended periods maintained relatively high levels of drug at this site. PMID- 7780201 TI - Tissue fibronectin is an endogenous ligand for galectin-1. AB - A 14K beta-galactoside-binding lectin (galectin-1) is present in many animal tissues. In a search for endogenous ligands, we surveyed galectin-1-binding proteins in human placenta. Extract of human placenta with 2 M urea was applied to a Sepharose 4B column conjugated with galectin-1 purified from frog (Rana catesbeiana) eggs. Two major proteins eluted with 100 mM lactose from the column bound fraction showed apparent molecular masses of 220 and 180 kDa on SDS-PAGE under reducing conditions. Western blotting analysis using monoclonal antibodies indicated that these proteins were fibronectin and laminin, respectively. Most placental and amniotic fibronectins bound strongly to the column, whereas almost all plasma fibronectin passed through the column. The galectin-1, fibronectin and laminin were immunohistochemically shown to be co-localized in the extracellular matrix of placental tissue. In a cell attachment assay, rhabdosarcoma cells adhered to a plate coated with placental fibronectin, even in the presence of GRGDS peptide, if galectin-1 were also present. This adhesive effect of galectin 1 was inhibited by lactose. These results indicate that tissue fibronectin, as well as laminin, serve as endogenous ligands for galectin-1, suggesting that galectin-1 may play a role in assembly of the extracellular matrix, or in the control of cell adhesion based on lectin-extracellular matrix interaction. PMID- 7780203 TI - Pleiotropic effect of fluoranthene on anthocyanin synthesis and nodulation of Medicago sativa is reversed by the plant flavone luteolin. PMID- 7780204 TI - Measurement of total polychlorinated biphenyls (PCBs) in catalytic combustion effluents using a simple HPLC procedure. PMID- 7780202 TI - Dodecyl-beta-D-maltoside as a substrate for glucosyl and xylosyl transfer by glycogenin. AB - Glycogenin is the core protein of glycogen proteoglycan and is, at the same time, a self-glucosylating enzyme which catalyses early glucosyl transfer steps in the biosynthesis of glycogen. In the course of this process, glycogenin is glucosylated progressively until an oligosaccharide containing 8-11 glucose residues has been formed. Although glycogenin, under physiological conditions, is both enzyme and acceptor in the glucosyl transfer reactions, it is also capable of utilizing p-nitrophenyl-linked malto-oligosaccharides as exogenous acceptors. In view of the potential usefulness of exogenous acceptors in the study of the mechanism of the glycogenin reaction, we have expanded the search for such compounds and report here that several alkyl glucosides and alkyl maltosides may serve as acceptors in glucosyl transfer by beef kidney glycogenin. Dodecyl-beta-D maltoside (Km approximately 100 microM) was the most effective acceptor among the compounds tested and yielded 30 times as much product as p-nitrophenyl-alpha maltoside. Substantial product formation was also observed with tetradecyl-beta-D maltoside and octyl-beta-D-maltoside (39 and 22%, respectively, of the value measured for dodecyl-beta-D-maltoside). It was further demonstrated that dodecyl beta-D-maltoside served as an acceptor in the transfer of xylose from UDP-xylose, indicating that the exogenous substrate behaved similarly to glycogenin itself in this regard. Dodecyl-beta-D-maltoside has already proven useful in the development of a simple glycogenin assay, and it is further suggested that this and related compounds may be active in vivo and in cell culture as artificial initiators of glycogen synthesis. PMID- 7780205 TI - Polyclonal antibody-based ELISA for triasulfuron. PMID- 7780206 TI - 32P-postlabeling determination of DNA adducts in the earthworm Lumbricus terrestris exposed to PAH-contaminated soils. PMID- 7780207 TI - Developmental hazard assessment with FETAX: aerobic metabolites in bacterial transformation of naphthalene. PMID- 7780208 TI - Effects of sterilization methods on the physical characteristics of soil: implications for sorption isotherm analyses. PMID- 7780209 TI - Use of toxicity identification evaluation procedures in the assessment of sediment pore water toxicity from an urban stormwater retention pond in Madison, Wisconsin. PMID- 7780210 TI - Exposure and effects of oilfield brine discharges on western sandpipers (Calidris mauri) in Nueces Bay, Texas. PMID- 7780211 TI - Acute and chronic toxicity of the thiocarbamate herbicide, molinate, to the cladoceran Moina australiensis Sars. PMID- 7780213 TI - Organochlorine compounds in fish from a farming station in the municipality of Paez, state of Zulia, Venezuela. PMID- 7780212 TI - Salt induced changes in the growth of Chlorococcum humicolo and Scenedesmus bijugatus under nutrient limited cultures. PMID- 7780214 TI - In vivo metabolism of pentachlorophenol and aniline in Arctic charr (Salvelinus alpinus L.) larvae. PMID- 7780215 TI - Relative sensitivity of some selected aquatic organisms to phenol. PMID- 7780216 TI - Tissue distribution and histopathological effects of dietary methylmercury in benthic grubby Myoxocephalus aenaeus. PMID- 7780217 TI - Ultrastructural and biochemical effects of 3-methylcholanthrene in rainbow trout. PMID- 7780219 TI - Excretion of intracorporeal cadmium with S-benzoylthiamin monophosphate. PMID- 7780218 TI - Metabolism of 3,5-di-t-butyl-4-methylphenyl N-methylcarbamate, Terbucarb, on isolated rat hepatocytes. PMID- 7780220 TI - Effect of pre-exposure to cadmium and silver on nickel induced toxic manifestations in mice: possible role of ceruloplasmin and metallothionein. PMID- 7780221 TI - Effect of dietary phytic acid and cadmium on the availability of cadmium, zinc, copper, iron, and manganese to rats. PMID- 7780222 TI - Suppression of cellular immune responses in BALB/c mice following oral exposure to permethrin. PMID- 7780223 TI - Cadmium contamination of wood ash and fire-treated coniferous humus: effect on soil respiration. PMID- 7780224 TI - Lead uptake from beer in India. PMID- 7780225 TI - Postoperative changes in plasma tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. AB - To clarify the changes which occur postoperatively in intravascular fibrinolysis, plasma levels of tissue-type plasminogen activator (t-PA) antigen, the total plasminogen activator inhibitor type-1 (PAI-1) antigen, and the t-PA-PAI-1 complexes were assayed in this study. Blood samples were taken the morning before surgery, then at 0, 12, 24, 36, 60, 108, and 156 h postoperatively in ten patients who underwent radical surgery for thoracic esophageal cancer. The plasma levels of the t-PA and total PAI-1 antigens, and the t-PA-PAI-1 complexes were then measured by enzyme immunoassay. The plasma t-PA and total PAI-1 levels increased significantly in the immediate postoperative period, the percent increase of the latter being much greater than that of the former. Moreover, the calculated free t-PA antigen level was decreased throughout the postoperative period, suggesting postoperative hypofibrinolysis. The platelet count and neutrophil elastase level were significantly correlated with the free t-PA antigen level at r = 0.630, P < 0.001, and r = -0.447, P < 0.01, respectively. The results of this study indicated that post-operative hypofibrinolysis caused by the increased synthesis of PAI-1 may enhance postoperative hypercoagulability, and this may lead to the development of organ damage. Thus, the concentration of the PAI-1 antigen may be a potentially important index for the prediction of postoperative illness. PMID- 7780226 TI - A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis. AB - Because myasthenia gravis (MG) is frequently associated with thymoma, in this study the histological patterns of thymomas from 11 patients with MG (group A) were compared with those from 8 patients without MG (group B). An immunohistochemical examination was also conducted to determine whether the thymoma associated with MG is the site where autoantibodies are produced or secreted. Lymphoid follicles (LFs) and medullary differentiation (MD) were histologically evident only in group A in 4 and 5 patients, respectively, but were completely absent in group B. Moreover, an elevated serum antiacetylcholine receptor antibody titer was found in group A. Typical LFs were histologically and phenotypically similar to the lymph follicles seen in reactive lymph nodes. The number of cells expressing the B-cell antigen differed between groups A and B in terms of IgM- or IgD-bearing cells in the mantle zones and LN1-positive cells in the germinal centers of LFs. Thus, it is thought that LFs consist of B cells under stimulatory conditions and that these B cells may have the potential to produce autoantibodies in MG; however, since the differentiation of these Ig bearing cells to plasma cells was hardly evident, the thymoma itself is possibly not the site of autoantibody production or secretion in patients with MG. PMID- 7780227 TI - Pathophysiology of dogs after 84% hepatectomy with emphasis on prostaglandin metabolites and the effect of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analog. AB - The pathophysiological conditions following 84% hepatectomy were examined in terms of the changes in thromboxane A2 (TxA2) and prostaglandin I2 (PGI2) in a canine model. OKY-046, a TxA2 inhibitor, and OP-2507, a PGI2 analog, were administered to evaluate the possibility of extending hepatic resection. The 2 week survival rate following 84% hepatectomy significantly improved after the administration of OKY-046 and OP-2507, from 12.5% to 58.3% and 75.0%, respectively. Furthermore, OP-2507 significantly improved impaired hepatocyte and sinusoidal endothelial cell function after 84% hepatectomy, resulting in a satisfactory recovery to the preoperative levels. Within 24 h after 84% hepatectomy, the plasma levels of thromboxane B2 (TxB2) increased significantly, and the 6-keto-prostaglandin F1 alpha (6-KF) levels became slightly elevated. OKY 046 and OP-2507 decreased TxB2 and increased 6-KF in the plasma, resulting in the maintenance of sufficient blood flow in the portal vein and hepatic tissue and the mitigation of microcirculatory disorders. Moreover, the cytoprotective effects of the two drugs inhibited functional impairment of the residual liver. In conclusion, abnormal prostaglandin metabolites were produced after 84% hepatectomy, being involved in residual liver disorders. However, the administration of either an inhibitor of TxA2 synthesis or a PGI2 analog ameliorated the functional impairment of the residual liver, which suggests their potential value for extending the resectability of the liver from what is presently feasible. PMID- 7780228 TI - Experimental study on chemotherapy using adsorbent charcoal with CDDP administered directly into the mediastinum following esophagectomy. AB - In this study, 1500AA, an activated charcoal with a strong affinity for the lymphatic system, was examined for its ability to deliver chemotherapy to metastatic lymph nodes. First, the anticancer effect on metastatic lymph nodes was assessed in an experiment using the mouse mammary tumor, MM48. Pathological examination of the inguinal lymph nodes revealed a metastatic rate of 50% in the group given cisplatin (CDDP)-saline, but 20% in the group given CDDP-charcoal. Next, in a canine model, CDDP dissolved in normal saline was administered directly into the mediastinum, and CDDP was given with fine particles of activated charcoal in the same manner in the other group. The concentration of CDDP in the lymph nodes and the plasma rapidly increased to peak in 10 min in the CDDP-saline group, whereas it increased slowly to peak in 20-30 min in the CDDP charcoal group. Moreover, the CDDP-charcoal group was found to have a much higher concentration of CDDP in the lymph nodes than the CDDP-saline group. PMID- 7780229 TI - The effects of calcium antagonists and prostaglandin E1 on isolated canine coronary arterial tension. AB - The effects of calcium antagonists (nifedipine, nicardipine, diltiazem, and verapamil) and prostaglandin E1 (PGE1) on the tension of isolated canine coronary arterial strips were studied. In a solution containing 20 mEq/L of K+, 127 mEq/L of Na+, the tension was increased by 500-1,000 mg with 4 mEq/L of Ca2+. This increase in tension was suppressed by Ca-antagonists and PGE1 dose-dependently. Nifedipine 10(-5) M, nicardipine 3 x 10(-7) M, diltiazem 3 x 10(-6) M, and verapamil 3 x 10(-6) M completely suppressed the increased tension. The maximal suppression of the tension produced by PGE1 was about 40% at 10(-10) M. In 20 mEq/L K+ solution (0 mEq/L Ca2+, 37 degrees C), the reduction of the Na+ concentrations from 127 mEq/L to 12 mEq/L increased the tension by 50 to 100 mg. This increase in tension was not suppressed by Ca-antagonists or PGE1. In conclusion, this study demonstrated that Ca-antagonists and PGE1 suppressed an increase in the tension caused by Ca2+ but did not suppress an increase in the tension caused by Na+ reduction. PMID- 7780230 TI - The development of a small bowel volvulus in the early postoperative period following a distal gastrectomy: report of a case. AB - A 51-year-old Japanese man who underwent a standard distal gastrectomy for cancer of the stomach developed abdominal pain when oral intake was commenced on the 6th postoperative day after an uneventful postoperative course. Complete obstruction of the jejunum led to a sudden deterioration in his general condition and a laparotomy was performed, revealing counterclockwise rotation of the mesenterium. The necrotic portion of the small intestine was removed, while 10 cm of the upper jejunum and 100 cm of the terminal ileum were preserved. His second postoperative course was uneventful apart from the development of "intestinal hurry," which is now under medical control 9 months after his second laparotomy. PMID- 7780231 TI - Pediatric spigelian hernia: reports of three cases. AB - We herein report three pediatric cases of spigelian hernia involving a 6-month old girl, an 8-month-old girl, and a 3-year-old boy. This is a rare condition with only 20 children (12 boys and 8 girls) younger than 15 years of age previously reported in the literature. Their ages ranged from 6 days to 15 years. The hernia was situated on the right side in six cases, on the left side in nine, and was bilateral in four (with one case unreported). Among these, four cases were caused by trauma and one case by a postoperative complication. Our first and third cases were spontaneous, while the second case was a postoperative lateral ventral hernia. The first and second cases were associated with ipsilateral mediastinal neuroblastoma. No previous report of spigelian hernia has been associated with mediastinal neuroblastoma. We suspected that muscle atrophy caused by the neuropathy of the ninth to twelfth intercostal nerves may have been the cause of the hernia. These two cases are thus believed to be the first such cases to be reported. PMID- 7780233 TI - Multiple pulmonary hamartomas: report of a case. AB - Among lung tumors, multiple hamartomas are uncommon while multiple chondromatous hamartomas are extremely rare, with only 12 cases having been previously reported. A case of multiple pulmonary chondromatous hamartomas in a 58-year-old Japanese man who has been followed up for 28 years is herein presented. PMID- 7780232 TI - Gastrocolic fistula originating from transverse colon cancer: report of a case and review of the Japanese literature. AB - A 72-year-old woman was admitted to our hospital complaining of loss of weight, general fatigue, and upper abdominal pain. Barium studies suggested that a fistula was present between the proximal transverse colon and the stomach which originated from a carcinoma of the colon. A plain computed tomography (CT) scan confirmed the presence of a gastrocolic fistula. A two-thirds distal gastrectomy and right hemicolectomy with a resection of a bulky tumor in the mesocolon were performed en bloc. Histological examination revealed a well-differentiated adenocarcinoma of the transverse colon which was involved with the wall of the stomach. We were able to obtain information on 14 previous cases of gastrocolic fistula originating from transverse colon cancer in the Japanese literature, including the present case. The most common symptom was abdominal pain (64%). A preoperative diagnosis of fistula was confirmed in 10 of the 11 cases examined by barium studies. A plain CT and a CT scan after the barium studies may also be helpful in detecting fistula formation. A fistula between the carcinoma of the middle or distal transverse colon and the stomach was found in 13 of 14 cases, but not in our case. Only one case lived longer than 9 years, even though a surgical resection was possible in 9 of 11 cases. PMID- 7780234 TI - Isolated dissecting aneurysm of the common iliac artery: report of a case. AB - Isolated dissecting aneurysms of the peripheral arteries which are not accompanied by a dissecting aneurysm of the aorta are rarely observed. We report herein the unusual case of a 54-year-old man in whom an isolated common iliac aneurysm was found to be caused by isolated dissecting aneurysms of the left common iliac artery. PMID- 7780235 TI - Clostridial gas gangrene associated with congenital generalized lipodystrophy: report of a case. AB - Congenital generalized lipodystrophy (CGL) is a rare disease, the main symptoms of which are a reduction of systemic subcutaneous fat, characteristic facial features, hypertrichosis, and insulin-resistant diabetes. We report herein the unusual case of a 25-year-old man with CGL in whom gas gangrene developed, an association which has never before been encountered. PMID- 7780236 TI - Anal metastasis from carcinoma of the lung: report of a case. AB - We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported. PMID- 7780237 TI - Obstructive jaundice caused by a cholesterol polyp of the gallbladder: report of a case. AB - We present herein the case of a 34-year-old man in whom obstructive jaundice was found to be caused by an impacted detached cholesterol polyp. A cholecystectomy with exploration of the common bile duct was performed after ultrasonography showed cholesterol polyps and stones in the gallbladder. Intraoperative cholangioscopy demonstrated an impacted cholesterol polyp at the distal end of the common bile duct which appeared to be detached from the gallbladder. To our knowledge, this is the first report of an impacted detached cholesterol polyp causing obstructive jaundice. PMID- 7780238 TI - Distal arterial reconstruction using Esmarch's bandage technique to salvage upper extremity function in thoracic outlet syndrome caused by cervical ribs: a report of two cases. AB - We present herein the cases of two patients with thoracic outlet syndrome (TOS) who required arterial reconstruction due to gangrene of the fingers and/or hand. In both patients, the cervical ribs had produced intimal injury of the subclavian arteries, and the successive distal arterial embolism brought about severe ischemia of the affected upper extremity. To treat the TOS, the cervical ribs were resected through a supraclavicular incision. In the first patient, arterial reconstruction was performed from the subclavian artery to the radial collateral artery, a branch of the deep brachial artery, which resulted in minimizing amputation of the gangrenous hand. In the second patient, resection and direct anastomosis of the injured subclavian artery were performed, and bypass surgery from a brachial artery to an interosseous artery was carried out, preserving finger function. Reversed saphenous vein grafts were utilized and Esmarch's bandage technique was applied as a substitute for a vascular clamp in both patients. Following these case reports, we discuss the technique of performing distal bypass in the upper extremities and comment on the usefulness of Esmarch's bandage technique for preserving upper extremity function. PMID- 7780239 TI - Idiopathic portal hypertension in renal transplant recipients: report of two cases. AB - We present herein the cases of two patients who developed idiopathic portal hypertension (IPH) following renal transplantation. Both patients had been treated with azathioprine and prednisolone for 6 years and 4 months and for 4 years and 7 months, respectively, and presented with splenomegaly and thrombocytopenia suggesting hypersplenism. Celiac angiography showed a dilated splenic artery and vein in both patients. When the splenic artery was obliterated with a balloon catheter in case 1, the portal venous pressure decreased from 51 cmH2O to 36 cmH2O, and the direction of the superiomesenteric venous blood flow became hepatopetal rather than hepatofugal. These results suggested that the spleen might have played an important role in the development of IPH in these two patients. A splenectomy was therefore performed, immediately following which the portal venous pressure decreased remarkably, and the esophageal varices disappeared during the postoperative follow-up period. Microscopic examination of liver biopsies taken at the operation revealed lymphoplasmacytic infiltration with bile duct hyperplasia but no evidence of periportal fibrosis, and electron microscopy demonstrated very mild perisinusoidal fibrosis. Thus, the histological changes seen in the livers of these patients seemed not to have caused the portal hypertension. In conclusion, although few patients develop IPH after renal transplantation, we should be aware of its possibility and consider splenectomy as the treatment of choice. PMID- 7780241 TI - Interleukin-1 receptor antagonist in the fetomaternal compartment. AB - Interleukin-1 (IL-1) is a major mediator in infections and inflammation. Interleukin-1 receptor antagonist (IL-1ra) opposes the actions of IL-1. IL-1ra is present in exceptionally high concentrations in third trimester amniotic fluid. We studied IL-1ra in amniotic fluid, fetal serum and newborn urine. The concentrations of IL-1ra in amniotic fluid at mid-trimester and at 25-41 gestational weeks were 6.6 +/- 0.5 ng/ml (n = 30) and 100 +/- 4 ng/ml (n = 202), respectively. At mid-trimester, amniotic fluid IL-1ra was not dependent on fetal gender, whereas during the third trimester IL-1ra was higher in female- than in male-bearing gestations. Urine of normal term newborns during the first day of life contained a very high concentration of IL-1ra (125 +/- 16 ng/ml, n = 50). Urinary concentration in female newborns was significantly higher than that in male newborns (202 +/- 19 ng/ml, n = 25 versus 49 +/- 14 ng/ml, n = 25). IL-1ra concentration in fetal serum at 22-36 gestational weeks was 0.50 +/- 0.07 ng/ml (n = 31) and at term 1.5 +/- 0.3 ng/ml (n = 17). Serum concentrations were not gender-dependent. The gender differences in IL-1ra concentrations may in part explain the lower susceptibility of female fetuses to infection. PMID- 7780242 TI - Breast milk beta-glucuronidase and prolonged jaundice in the neonate. AB - Breast milk samples from mothers of breast-fed, healthy, term newborns with unexplained prolonged jaundice were analyzed for beta-glucuronidase activity. Mean enzyme activity was 75.7 +/- 34.5 modified Sigma units/ml in the breast milk samples ingested by the study group of jaundiced babies (n = 25) and 82.2 +/- 40.1 modified Sigma units/ml in the samples ingested by the control group of non jaundiced babies (n = 20) (p > 0.05). Enzyme activities at 2, 3 and 4 postnatal weeks were 101.0 +/- 39.9, 66.0 +/- 20.7 and 57.0 +/- 22.4 modified Sigma units/ml in the study group and 87.9 +/- 36.1, 58.5 +/- 15.0 and 88.3 +/- 49.1 modified Sigma units/ml in the controls. The differences were not statistically significant (p > 0.05). We conclude that breast milk beta-glucuronidase activity may be a contributory factor, in the presence of other variables, in hyperbilirubinemia but it is neither the main nor the only cause of prolonged jaundice in neonates. PMID- 7780243 TI - Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents. AB - In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3 mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5 mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5 mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2 mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8 mg/kg/day) was significantly higher than in the group fed breast milk (+8.6 mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/l), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/l). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis. PMID- 7780240 TI - Quadruple cancer including Bowen's disease after arsenic injections 40 years earlier: report of a case. AB - This report describes the successful treatment of quadruple cancer including Bowen's disease in a 71-year-old man who had been given injections of salvarsan, an arsenic compound, for syphilis more than 40 years earlier. Resection of a skin lesion on his chest subsequently confirmed a diagnosis of Bowen's disease, 3 years after which he was operated on for concurrent gastric cancer and sigmoid colon cancer. A fourth cancer was discovered on his left vocal cord 2 weeks after this operation; it was resected 2 years later. A discussion of multiple malignant neoplasms and the possible relationship between arsenic and cancer is presented following this case report. PMID- 7780244 TI - Developmental maturation of gastro-oesophageal reflux in preterm infants. AB - The frequency and duration of gastro-oesophageal reflux were examined in 40 preterm infants and compared with a previously published healthy cohort of 74 term infants. Selection required that the infants were born between 24 and 32 weeks' gestation, had a normal head ultrasound and were studied at term post menstrual age. Multi-channel pen recordings of sleep state, movement, breathing and acid reflux were made. In term and preterm infants the frequency and duration of reflux were greatest in active sleep, rare in quiet sleep and significantly less in preterm than term infants in wakefulness and active sleep (p < 0.05). The fewer and shorter episodes in preterm infants could not be explained by sleep state movement, gestational or postnatal age, days intubated, days on oxygen or the lowest pH of reflux episodes. PMID- 7780245 TI - Neonatal herpes simplex: clinical findings and outcome in relation to type of maternal infection. AB - In 39 mothers of children with neonatal herpes simplex virus infection, maternal infection was serologically characterized retrospectively and was related to maternal clinical symptoms and to the clinical findings and outcome in the child. Thirteen mothers had a primary infection (six type 1, seven type 2), mostly with clinical symptoms. The mean age of onset of the disease of the infants was 7 days and a disseminated disease was most commonly found. Most of the type 1-infected children recovered completely, whereas all but one of the type 2-infected children died. Twenty mothers had a recurrent (2 type 1, 18 type 2) and 4 an intermediate infection (primary type 2, prior infection with type 1), mostly asymptomatic. Their children had a localized disease (of the skin-eye-mouth or the central nervous system) with onset at a mean age of 14 or 13 days, respectively. The frequency of neurological sequelae was high. Two mothers had no serological signs of herpes infection. PMID- 7780247 TI - Severe mental retardation in 2 to 24-month-old children in Lahore, Pakistan: a prospective cohort study. AB - Severe mental retardation (developmental quotient (DQ) < 50) was investigated in 1303 children from 2 to 24 months of age, born during 1984-87 in four population groups representing different socio-economic levels in and around Lahore, Pakistan. The incidence per 1000 live births was 22 in the periurban slum, 9 in the urban slum, 7 in the village and 4 in the upper middle class group. The aetiology was prenatal in 79%, perinatal in 14% and untraceable in 7% of cases. Down's syndrome was the most common cause of severe mental retardation (36%). Impairments were studied at 2 years of age. Impairment of language was present in all, while locomotor dysfunction was seen in 89% of cases. Epilepsy and cerebral palsy were each present in 22% of cases. Mortality among these severely mentally retarded children was 36%. PMID- 7780248 TI - A nutrition study in juvenile elite gymnasts. AB - Twenty-two female teenagers engaged in elite gymnast training and 22 healthy girls of comparable age were studied with regard to nutritional intake. The mean daily intakes of most nutrients in both groups were in accordance with the Swedish Nutritional Recommendations; exceptions were iron and dietary fibre which were too low in both groups. The individual variation was large in both groups and many subjects had an intake below the nutritional recommendations. Both the gymnasts and the reference group had an energy intake significantly below the estimated energy need. The mean daily energy intake was 725 kcal less than the energy need in the gymnast group and 450 kcal less in the reference group. The clinical investigation revealed that several gymnasts had delayed menarche or irregular menstruation as well as less body fat than the reference group. Among the gymnasts, girls with a regular menstrual pattern had more body fat than those who had not started to menstruate. The higher energy expenditure of the gymnasts could partly explain their smaller amounts of body fat, late pubertal development and menstrual patterns. PMID- 7780246 TI - A population-based study on the causes of mild and severe mental retardation. AB - The causes of mental retardation (MR) were studied as part of a multidisciplinary epidemiological case-control study in 151 mentally retarded patients identified by screening four age cohorts (12,882 children) at 8-9 years of age in the province of Kuopio, Finland. The causes of MR in 77 severely retarded (SD < or = 3 SD) and 74 mildly retarded (-2 > SD > -3) children were divided into pre-, peri , postnatal and unknown groups according to the probable time of onset. The causes were pre-, peri-, postnatal and unknown in 60%, 9%, 8% and 23%, and 22%, 1%, 3% and 74%, in the two populations, respectively. Genetic causes were found in 28% of all 151 cases; the three most common subgroups were trisomy 21, fragile X syndrome and aspartylglycosaminuria (13%, 4% and 2% respectively). The study design used provided reliable information on the causes of MR and also demonstrated those forms of genetic metabolic diseases typical of Finnish inheritance. PMID- 7780249 TI - Normative developmental behavior with implications for health and health promotion among adolescents: a Swedish cross-sectional survey. AB - I describe behavior with impact on health in adolescents against the background of characteristics of the Swedish society and analyse possible areas for improvement. A total of 4500 adolescents, aged 13-18 yr, in seven areas answered an anonymous questionnaire. Their socioeconomic backgrounds reflected mainstream adolescents. The response rate was 80-85%. Questions concerned health habits, exploratory behaviors regarding sexuality, use of alcohol and tobacco, problem behaviors, such as getting drunk, and life quality. There was very little experimentation with regard to health habits learned in childhood. Rapid adaptation to adult life-styles occurred, which was similar in both sexes in the younger age groups, but there were significant differences among older students. Alcohol use is of considerable concern. Adolescent prediction of future behavior indicated that negative behaviors require intervention. Parental influence on adolescent behavior needs to be explored. Peer groups could be an additional area for intervention. PMID- 7780250 TI - Hypotonic oral rehydration solution in acute diarrhoea: a controlled clinical trial. AB - In a controlled trial, a hypotonic oral rehydration solution (ORS) (Na+67, K+20, Cl-66, citrate 7, glucose 89 mmol/l osmolality 249 mosmol/kg) was compared with a standard WHO-ORS (Na+90, K+20, Cl-80, citrate 10, glucose 111 mmol/l, osmolality 311 mosmol/kg) in 60 children aged 5-24 months with acute watery diarrhoea. In the hypotonic ORS group, stool frequency, proportion of children who vomited, ORS requirements and purging rate over 24-48 h were reduced by 33% (p = 0.01), 30% (p = 0.02), 21% (p = 0.067) and 21% (p = 0.03), respectively. The proportion of children who vomited and the purging rate over 48 h were reduced by 23% (p = 0.03) and 10% (p = 0.097), respectively. Serum electrolytes after 48 h were comparable. The beneficial effect of hypotonic ORS was most marked in, and largely contributed by, the subgroup negative for rotavirus. PMID- 7780251 TI - Anti-endomysium and anti-gliadin antibodies as serological markers for coeliac disease in childhood: a clinical study to develop a practical routine. AB - Anti-gliadin and anti-endomysium antibodies were analyzed in 174 children with suspected or verified coeliac disease with the aim of developing a practical routine. The biopsy was performed without knowledge of the antibody levels. To screen for coeliac disease is children younger than 2 years, we suggest the use of IgA anti-gliadin antibodies, giving a sensitivity of 100% and a specificity of 86%. In older children both tests should be used in parallel, i.e. a biopsy should be performed if at least one of the tests is positive, giving a sensitivity of 98% and a specificity of 81%. To avoid unnecessary biopsy before mucosal relapse can be demonstrated during gluten challenge in a child without clinical symptoms, we suggest that the tests are used as serial testing, i.e. a biopsy should be performed if both tests are positive. PMID- 7780252 TI - Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis. AB - Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 +/- 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone Bn-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values stimulated levodopa GH peaks (pathological values (< 10.0 micrograms/l) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH-nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 +/- 0.9 cm/year; 6 months 6.4 +/- 1.9 cm/year, p < 0.001 versus baseline; 12 months 6.0 +/- 1.3 cm/year, p < 0.0001 versus baseline). There was a significant increase in height SDS for bone age (baseline -1.6 +/- 0.5 SDS; 12 months -1.04 +/- 0.6 SDS; p < 0.002) and in predicted adult height (baseline 152.0 +/- 3.6 cm; 12 months 155.9 +/- 3.4 cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment. PMID- 7780253 TI - Acute asthma, salbutamol and hyperglycaemia. AB - The effects of frequent high-dose nebulized salbutamol on plasma glucose concentrations were studied in 12 children (mean age 60 months) with acute severe asthma. There was a significant difference between mean initial glucose levels and peak levels. We conclude that hyperglycaemia can be produced in children as a result of nebulized salbutamol. PMID- 7780254 TI - Spinal posture during pubertal growth. AB - A cohort of children was followed-up annually from a mean age of 10.8-13.8 years to determine the development of their posture. Of the sample of 1060 children, 847 (79.9%) participated in the final examination. Thoracic kyphosis and lumbar lordosis were measured annually with a spinal pantograph. Those children whose thoracic kyphosis in pantography was more than 35 degrees at entry and 45 degrees or more at the final examination underwent a lateral standing radiograph. The 3 year incidence of Scheurermann's disease was 0.4%. The mean thoracic kyphosis increased and the mean lumbar lordosis decreased with age in both sexes, but these changes were not constant. Thoracic kyphosis was most pronounced at a mean age of 12.8 years and lumbar lordosis was least pronounced at a mean age of 13.8 years. In accordance with the literature, the wide individual variation found in this study for both thoracic kyphosis and lumbar lordosis during the pubertal growth period was mainly physiologic. PMID- 7780256 TI - Trends in survival after childhood cancer in Denmark, 1943-87: a population-based study. AB - Survival from cancer in childhood and adolescence was studied in a population based series of 8312 cases in children aged 0-19 years notified to the Danish Cancer Registry during 1943-87. During the first period (1943-72), 5-year survival rates from all malignant neoplasms increased from 23% (1943-52) to 33% (1963-72). The greatest improvement was seen during the period 1973-87 when 5 year survival rates reached 64% (1983-87). Between 1973-77 and 1983-87, 5-year survival rates increased from 32% to 62% for leukaemia, from 40% to 70% for acute lymphoblastic leukaemia, from 35% to 54% for non-Hodgkin's lymphoma, from 50% to 66% for central nervous system neoplasms and from 25% to 49% for bone tumours. An improvement in 5-year survival rates from Wilms' tumour was seen between 1960 (19%) and 1980 (81%). Up to 1972, the 5-year survival rate from germ-cell neoplasms was approximately 40%; among patients diagnosed in 1983-87, 76% survived for 5-years. Annual lethality decreased by 2.5% for all malignant neoplasms in 1943-72 and by 4.4% in 1972-87. Lethality was similar for boys and girls during the period 1943-72, but was significantly lower for girls subsequently. A marked effect of age at diagnosis was seen in the early registration period, where lethality rate for the age group 0-9 years was substantially higher compared with that in the age group 10-19 years. This inequality persisted only for children less than 2 years of age at the time of diagnosis in the later period. PMID- 7780255 TI - Study of lumbar spine bone mineral density in obese children. AB - Bone mineral density (BMD) was studied in 59 obese children (mean (+/- SD) age 11.8 +/- 2.7 years) at the start of dietary treatment and compared with a control group, matched for sex, age and body height. Determinations of BMD were made at the level of the lumbar spine (L2-4) by a commercial dual photon absorptiometer (Novolab 22A). Mean (+/- SD) BMD of the obese children (0.68 +/- 0.12 g hydroxy appetite/cm2 (gHA/cm2)) was similar to that of the control group (0.70 +/- 0.16 gHA/cm2). As in normal children, BMD of obese children was highly correlated with age (r = 0.70), body height (r = 0.65) and body weight (r = 0.55). The highest values for BMD were found in obese adolescents with the most advanced pubertal status. No sex difference in BMD was seen in the obese children when pubertal stage was taken into account. Lumbar spine BMD corrected for age, was not related to the degree or duration of obesity. No influence of physical activity on spinal mineralization could be demonstrated in the obese group. In conclusion, obese children present with normal lumbar spine BMD. PMID- 7780257 TI - Total body irradiation: a neuropsychological risk factor in pediatric bone marrow transplant recipients. AB - Bone marrow transplantation (BMT) involves conditioning with cyclophosphamide and, for leukemic patients, total body irradiation (TBI). Based on the concern that this may lead to later neuropsychologic impairment in children, a longitudinal study was conducted. Thirty pediatric bone marrow transplant recipients, treated for leukemia or severe aplastic anemia (SAA), and their sibling donors, were given a neuropsychological examination in 1986 and 1988. A third follow-up study of patients treated before 12 years of age was undertaken in 1990-91. We present longitudinal data on patients treated with BMT when 3-11 (n = 15) and 12-17 (n = 11) years old. No neuropsychological deficits were found in the older group, or among non-irradiated SAA patients. In the first follow-up, children treated with BMT, including TBI at 3-11 years of age, performed less well than donors on tasks involving perceptual and fine-motor speed. In the second follow-up, this group of patients also demonstrated a slight deficit in non-verbal problem solving. An additional relative decline in verbal reasoning was noted in the third follow-up, 5.5-10 years after treatment. Alertness to signs of developmental difficulties in children treated with BMT, including TBI, is recommended. PMID- 7780258 TI - Automatic needle insertion diminishes pain during growth hormone injection. AB - Non-compliance in children receiving growth hormone (GH) treatment is often caused by pain on injection and difficulties in administration of GH. It has been suggested that automatic needle insertion diminishes pain perception. We quantitatively measured pain intensity on injection with two prototype pens for GH administration, providing either manual or automatic sc needle insertion, using a combined visual analogue/facial scale and a five-item scale in 18 children. With the automatic pen there was a significantly lower maximum pain score compared with the manual pen (median 28.5 versus 52.0 mm) as well as a lower mean pain score (mean 13.7 versus 23.5 mm). The five-item scale revealed that automatic needle insertion was significantly less painful than manual insertion and 13 patients chose to continue treatment with the automatic pen. In conclusion, pain during GH injection can be significantly diminished by automatic needle insertion, which may improve compliance in long-term GH treatment. PMID- 7780259 TI - Detection of resistance to thyroid hormone by cord blood screening. PMID- 7780260 TI - The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). AB - The presenting features of 39 patients with mucopolysaccharidosis (MPS) type IH are described. The mean age at diagnosis was approximately 9 months and it is difficult to see how this can be reduced without consideration of newborn screening. An earlier age at diagnosis is likely to lead to better results following therapy such as bone marrow transplantation. Clinical features which should arouse suspicion of MPS IH include frequent ENT surgery and recurrent herniae. Clinical vigilance is needed for early diagnosis. PMID- 7780261 TI - Ganciclovir therapy of congenital human cytomegalovirus hepatitis. PMID- 7780262 TI - Recrudescence and relapse of meningococcal meningitis and septicaemia. AB - Three cases of recrudescence and relapse of Neisseria meningitidis group B meningitis and septicaemia are reported. The recrudescence and relapses could not be explained by infectious foci, increased bacterial penicillin resistance or immunological defects. As a supplement to antibiotic treatment, all three patients received corticosteroids for the initial 2 days of treatment, and this may have contributed to the unusual course of the disease in our patient. PMID- 7780263 TI - Persistent non-familial asymptomatic hyperphosphatasemia: a report on three cases. AB - Three male children, aged 9 days, 2 years and 13 years, were found to have elevated serum alkaline phosphatase (ALP) activity (hyperphosphatasemia) in the absence of disease. In these three cases, elevation of ALP activity had persisted for 6-10 years. These patients did not inherit the disease from their parents. Isoenzyme determination revealed a skeletal origin of the elevated ALP in the three patients. They were diagnosed as having persistent non-familial asymptomatic hyperphosphatasemia (PNAH) which differs from transient and persistent asymptomatic familial hyperphosphatasemia. Reviewing the literature, although the term PNAH had not been used, two similar cases have been reported in a 24-year-old female and in a 27-year-old female. PNAH may be another type of benign hyperphosphatasemia. PMID- 7780264 TI - Congenital misalignment of pulmonary vessels: an unusual syndrome associated with PPHN. AB - We report a case of misalignment of pulmonary vessels and review the clinical features of all 13 cases reported to date. All were term infants dying from severe persistent pulmonary hypertension of the newborn. We have identified a triad of features that will alert neonatal clinicians to the possibility of this diagnosis: association with other non-lethal congenital malformations; delayed onset of presentation (especially after 12h); and severe hypoxaemia refractory to conventional therapy. We recommend that any autopsy on newborn infants include a specific search for misalignment of pulmonary vessels to outline the pathophysiology and clinical significance of this disorder. PMID- 7780265 TI - Why must Indian diabetic children continue to have retarded growth? PMID- 7780266 TI - Plasma exchange in childhood Guillain-Barre syndrome. PMID- 7780268 TI - [Psychometric function of stereo disparity in normal persons]. AB - The accuracy and efficiency of threshold estimation depend on a priori knowledge of the shape of the psychometric function. Such knowledge is available for contrast detection and visual acuity, but not for disparity detection. METHODS: We studied the psychometric function for disparity detection in 26 visually normal, untrained observers by measuring detection rates over a wide range of disparities. In a two-alternative forced-choice (2AFC) task the subject had to decide whether the right or left of two vertical bars, differing in depth, was closer to them. An S-shaped Weibull function was fitted to each subjects's data using the maximum-likelihood procedure. RESULTS: In 21 of the 26 subjects the psychometric function rose with increasing disparities up to a level of about 100%. Five of the 26 subjects only reached hit rates clearly below 100% (66% to 82%), even at disparities well above the threshold. The mean slpe of the S-shaped psychometric function of disparity detection was much lower (1.2 Weibull units) than that known for visual acuity and contrast detection (about 3.0 Weibull units). The slope differed widely among subjects, but was not related to stereo acuity. CONCLUSION: For accurate and efficient estimation of stereo acuity, the shallow slope of the psychometric function requires more than 100 single trials around the threshold if a 2AFC procedure is used. In addition, several disparities well above the threshold must be presented in order to detect subjects who do not reach a hit rate of 100% at any disparity. Otherwise, stereo acuity would be underestimated in these subjects. PMID- 7780267 TI - [Experimental studies of locally generated focal VECP within the 30 degree visual field with LED]. AB - Measuring and evaluating locally generated VECP present a chance to overcome methodical restriction in conventional subjective perimetry. To achieve this, stimuli are required which ensure the generation of detectable responses under controlled scattered light influence. The suitability of LED for this task was studied. LED stimuli (lambda = 560 nm) were moved in steps of 3 degrees from 0 degree to 30 degrees on the horizontal meridian within a perimeter sphere. The stimuli were 0.8 degree and 1.7 degrees in size, 20 ms in duration and 0.5 Hz in frequency. The background illumination was 10 cd/m2. A total 467 responses recorded from 20 volunteers (age 26 +/- 2) known to be free of any visual field defect have been evaluated. Using only one LED (size 0.8 degree) VECPs are detectable in the visual field < 9 degrees exclusively. An increase of stimuli size to 1.7 degrees made the generation of detectable VECP within the peripheral visual field possible. Statistical evaluation (sign test) proved significantly that VECP can be reliably elicited under LED stimulation. LED (lambda = 560 nm) are suitable for the generation of localized VECP in the visual field up to an eccentricity of 30 degrees. PMID- 7780270 TI - [Aniseikonia reduces binocular summation in the VECP]. AB - The binocular summation effect of human VECP (increase in amplitude from about 4.0 microV to about 5.4 microV) was proved and optimized in 32 subjects. Stimulus parameters: TV steady-state pattern reversal (7.0 Hz); pattern size 1 degree; stimulus contrast 5% (higher stimulus contrasts reduced considerably the selectivity of the binocular summation effect); 96 sweeps averaging (Nicolet Compaq Four); position of electrodes: 10% and 30% above Protuberantia occipitalis externa of nasioninion distance. Aniseikonia of 7 to 52% was generated by means of small Galilei telescopes. Because of comparatively large interindividual variance within the series of subjects, no decrease in binocular VECP amplitude could be demonstrated at an aniseikonia less than 52%. On one woman subject, a significant reduction in amplitude (5% level) at 14%, 26% and 52% aniseikonia was apparent, but not at 7%. Thus, for this subject, it was possible to correlate the results with the clinically known limits of toleration for aniseikonia. This result was confirmed by more than 60% of the subjects in the test group. PMID- 7780269 TI - [Photo- and videographic determination of the dilatation deficit in differential diagnosis of Horner syndrome]. AB - Physiological anisocoria, a very frequent condition among normal subjects, must be differentiated from Horner's syndrome. Aside from a history including evaluation of older photographs, pharmacological pupil testing with cocaine eye drops has been the "gold standard". Measurement of dilation lag, occurring in Horner's syndrome, is much less common and normal values are missing. Therefore, we evaluated various photographic parameters for testing for the best parameter to discriminate Horner's syndrome (22 patients) from physiological anisocoria (16 patients). Additionally, we tested whether a commercially available camcorder is sufficient to record pupillary dilatation lag. An anisocoria of 0.6 mm or more 4s after switching off the illumination discriminates physiological anisocoria from Horner's syndrome with a sensitivity of 82% and a specificity of 69%. A dilatation speed of 1.1 mm/4 s shows the same ability to differentiate in anisocoria and does not provide any better results. Because of the good correlation between post-cocaine anisocoria and anisocoria after 4 s in darkness, photographic or videographic measurements of the pupillary dilatation lag may complete or in some cases even replace cocaine testing. PMID- 7780272 TI - [Effect of induced hyperglycemia on contrast sensitivity function in insulin dependent diabetic patients]. AB - Acute hyperglycemia in diabetes mellitus is often associated with transient subjective visual disturbances that have not yet been objectively evaluated. We used a contrast sensitivity (CS) test to assess functional visual disturbances in provoked hyperglycemia in 20 patients with well-controlled insulin-dependent diabetes (40 eyes) with no evidence of diabetic retinopathy and with intact visual acuity (age: 32 +/- 8.2 years, duration of diabetes: 11.4 +/- 7.3 years). The CS function was measured by using the CSV-1000 CS test, which is rapid and easily comprehended by the patient and encompasses four spatial frequencies, 3 (A), 6 (B), 12 (C) and 18 (D) cycles/degree. At each frequency, eight pairs of circular targets differing stepwise in contrast were presented simultaneously. The number of targets seen by each patient in the four spatial frequencies at euglycemic (116 +/- 14.7 mg/dl) and hyperglycemic (274 +/- 52 mg/dl) levels, expressed as the CS score, was recorded and afterwards analyzed. The differences in mean CS scores at the individual frequencies at euglycemic versus hyperglycemic levels were statistically significant (p < 0.001). Visual acuity remained stable during hyperglycemia. There was no significant difference in the amount of CS reduction between the group of patients that had had diabetes for a duration of more than 10 years and the group who had had diabetes for less than 10 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780271 TI - [Contrast sensitivity of visually handicapped patients]. AB - The contrast sensitivity of 41 patients with low visual acuity, as a result of age-related maculopathy, diabetic retinopathy or open-angle glaucoma, in most of them, was studied by means of the VISTECH test and the Buser LCS-test. The VISTECH test revealed reduced contrast sensitivity, especially at high frequencies. This reduction was marked in patients with diabetic retinopathy. Contrast on the color TV monitor was adjusted by the subjects. Yellow and green monitors were chosen equally often by the patients. A positive contrast (black text with light background) was preferred. The contrast required was noticeably higher than that required by subjects with normal eyes. PMID- 7780273 TI - [Glare adaptation for inhomogeneous glare distribution with respect to the dynamic components of the vision task]. AB - Basic investigations in the field of adaptation luminance were carried out using Holladay's visual threshold criterion. The connection between adaptation luminance LA, illumination at the spot in the eye EB1 and the angle of glare theta is LA = 9.2 x EB1 x theta -2 LA in cd/m2, Eb1 in 1x, theta in degrees. In most cases the investigations of adaptation luminance were also carried out under conditions of fixed view and static visual tasks. It is however, important to take into account the dynamic visual task and the adaptation process by determining the adaptation luminance, but very few measurements have been carried out under these conditions. For the results represented here the visual threshold was replaced by the readaptation time necessary for perception of movement direction of a striped pattern (dynamic) and with the idea of also comparing the perception of the slot location in a ring in the Landolt rings (static). The method of investigations was as follows: The subject adapts to the inhomogeneous field of luminance for which the adaptation luminance must be determined. Then in a dark surrounding field for comparison, the visual task is offered, and the readaptation time necessary for the fulfillment of the visual task is measured. This procedure is repeated with a homogeneous field of luminance. The luminance of a homogeneous field is equal to the adaptation luminance. If the readaptation times are equal, the inhomogeneous distribution of luminance has the adaptation luminance LA. The important difference in comparison to previous investigations is the inclusion of dynamic components (readaptation time and dynamic visual task).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780274 TI - [Sensitivity and specificity of masked field campimetry]. AB - Patients with circumscribed visual field defects are able to perceive the scotomata immediately while looking at randomly distributed black and white squares (12' x 12') flickering on a VDU with a high frequency (approximately 30 Hz), resulting in a stimulus field comparable to the white-noise field on a TV screen without reception. In 368 eyes of 368 patients with varying lesions of the visual pathway the results of white-noise field campimetry were compared with those of conventional threshold-related, slightly suprathreshold automated grid perimetry. Rate of detection (sensitivity) was 84.2% in conventional perimetry and 80.7% in white-noise field campimetry, respectively. The results are not significantly different (p > 0.1; McNemar test). Examinations in 198 eyes of 198 persons without any indication of a visual pathway defect allowed a definition of the normal range of white-noise field campimetry to be made. The specificity of this new method was 82.3%. The outcome of this most extensive study on sensitivity and specificity of noise field campimetry is compared with other publications. The results presented emphasize the capabilities of this new method as a screening test. They encourage the initiation of a field study using the noise field stimulus broadcasted to home TV sets. PMID- 7780276 TI - [The Freiburg Vision Test. Automated determination of visual acuity]. AB - The Freiburg Visual Acuity Test is an automatic computerized procedure for self administered measurement of visual acuity. Landolt-Cs are presented on a monitor in one of eight orientations. The subject presses one of eight buttons, which are spatially arranged according to the eight possible positions of the Landolt-C's gap. To estimate the acuity threshold, a best-PEST procedure is employed, assuming a psychometric function with a constant slope on a logarithmic acuity scale. The discreetness artifacts in computer monitors limit the presentation of small stimuli. By anti-aliasing (smoothing of contours by gray-shading), the spatial resolution was improved by a factor of four, such that the shape of Landolt-Cs with oblique gaps is adequate and visual acuities from 0.06 up to 3.6 can be tested at a distance of 5 m. PMID- 7780275 TI - [A new method for objective vision assessment using infrared nystagmography]. AB - Objective assessment of visual acuity (VA) is necessary in cases of malingering or poor cooperation in subjective VA evaluation. Based on Ohm's idea of the suppression of experimentally evoked optokinetic nystagmus (OKN), a new objective visual acuity test is presented. A commercially available system for monitoring eye movement (OBER2) allows the test to be performed on a standard PC with a minimum amount of time. A grating pattern moving horizontally on the screen evokes OKN, which is recorded by infrared nystagmography. Superimposed black optotypes of increasing size (brake marks) suppress OKN as soon as they are recognized. Eighty-two normal eyes with VA artificially reduced by different Bangerter dispersion foils (VA 0.04-1.6) and 152 eyes with visual disturbances (VA 0.04-1.0) of various etiologies were examined. The test allowed estimation of the least VA in steps of > or = 1.0, > or = 0.25, > or = 0.1, > or = 0.05. None of the eyes examined had a VA below these values when the OKN was suppressed by the referring brake mark. PMID- 7780277 TI - [Dapiprazol antagonizes tropicamide- and phenylephrine-induced mydriasis in the elderly]. AB - Dapiprazole eye drops were applied 1 h after topical tropicamide or phenylephrine instillation in 30 elderly subjects. Pupil diameter normalized much earlier than in controls receiving placebo. Dapiprazole constricted the tropicamide-dilated pupil by 1 mm after 1 h and normalized the pupil diameter of the phenylephrine dilated pupil within 1 h, whereas the pupils of the patients receiving placebo remained dilated. Intraocular pressure did not change; no major side effects were seen. PMID- 7780278 TI - [Sensitive physiologic perceptual tests for ocular side effects of drugs exemplified by various anticonvulsants]. AB - Advanced psychophysical tests, performed in 42 patients who have seizures, showed that the widely used antiepileptic drugs, diphenylhydantoin and carbamazepine, can specifically affect retinal function, while valproic acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 desature tests revealed an accumulation of errors along the tritan/tetartan axis and a high total error score. As shown by measurement of the so-called transient tritanopia and by determination of the spectral sensitivity, this blue vision defect is not only due to loss of postreceptoral interaction between long- and short-wavelength sensitive cones, but is also based on a disturbance in the receptor mechanism itself. The dark adaptation curve was not affected. As determined by cone flicker thresholds during dark adaptation, the inhibitory action of rods on cones is reduced. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to the normal population. The psychophysical methods provide a very sensitive test for early detection of drug-induced retinal dysfunction and allow clear differentiation between the loss of a receptor mechanism and a defect in the neuronal interaction between photoreceptors in the human visual system induced by antiepileptics. PMID- 7780279 TI - [Binocular photometer for measuring light perception in diseases of the visual pathway]. AB - In patients with a reduction in visual function because of optic nerve neuritis, light sensitivity is tested to detect differences between the right and left eye in combination with the swinging flashlight test and visual evoked potential (VEP). A binocular Zeiss microscope was modified to use integrated photometer controlled binocular stimulus fields and a central light system for fixation and variation of the contrast (background illumination). For exact binocular measurements of light sensitivity on both eyes, electronically controlled test fields (visual angle 5 degrees-20 degrees) guarantees only macular or overfoveolar stimulation. In addition, splitting the light for each stimulus field from only one halogen lamp guarantees wave-length-independent testing. Patients with various retinal diseases and neuritis nervi optici pathology were examined using pattern VEP, testing of the absolute lower threshold of light sensitivity, and binocular comparison over the range of luminous density. This binocular optical photometer system allowed minimal differences to be identified in the present visual function and after the eye had recovered from optic nerve neuritis. PMID- 7780280 TI - [Balloon dilatation of relative postsaccal lacrimal duct stenoses]. AB - In ten patients with incomplete postsaccal stenosis radiology examined by digital subtraction dacryocystorhinography, an overpressure ballooning was done with a small foot vessel balloon with hydrophilic surface under image intensiver control. The balloon was inflated with a diluted suspension for visualization of the balloon and widening of the stenosis. In eight patients recovery was continuous without any treatment, in one with topical application of vasoconstrictor eye drops. In one patient there was a recurrence. Balloon of incomplete postsaccal lacrimal pathway dilatation stenosis is an adequate and minimally invasive therapy. PMID- 7780281 TI - [Prevention of postenucleation syndrome: the hydroxylapatite silicone implant. Preliminary experimental studies and initial clinical experiences]. AB - An orbital implant after enucleation compensates for volume deficiency and increases prosthesis motility. In the literature, however, an extrusion rate of orbital implant between 10 and 25% is reported. Since the introduction of hydroxylapatic ceramics (HAC), these numbers have been reduced considerably. The HAC, which is derived from corals, has a rough surface and requires a scleral covering for implantation. The HAC, which is made in the laboratory, can be produced with smoother surfaces, so that a homoplastic covering is no longer mandatory. A composite implant was developed to improve prosthesis motility further. This consists of artificial HAC at its anterior surface to guarantee safe tissue integration; the posterior part of the implant is manufactured from silicon rubber to create a jointlike structure in Tenon's capsule. Integration of the porous HAC in the orbital soft tissues has been tested and confirmed by animal experiments. After 30 full HAC implants and 25 composite implants, only one extrusion occurred. In all other cases, compatibility proved to be excellent; transmission of the motility to the prosthesis was moderate to good. Examinations comparing prosthesis motility and computer tomographically evaluated implant motility enabled the analysis of deficits in motility transmission of the implant for the artificial eye. PMID- 7780282 TI - [Changes in orbital hemodynamics caused by nitroglycerin and nifedipine. A study using color duplex ultrasound]. AB - Color Doppler imaging has demonstrated orbital hemodynamic changes in diseases such as central vein occlusion, the ocular ischemic syndrome and diabetic retinopathy. Reports of pharmacologically induced changes are, however, rare and inconsistent. In order to verify the sensitivity of color Doppler imaging to demonstrate pharmacologically induced changes in orbital hemodynamics, nitroglycerin and nifedipine served as vasoactive agents with a clear pharmacological spectrum. Twelve healthy volunteers were examined before and after drug application. After the administration of 0.8 mg nitroglycerin, the end diastolic bloodflow velocity was increased in the central retinal artery (before: Vdiastolic 2.2 +/- 1.0 cm/s, after: Vdiastolic 3.1 +/- 1.1 cm/s) as well as the ophthalmic artery (before: Vdiastolic 5.8 +/- 1.7 cm/s, after: Vdiastolic 7.4 +/- 1.8 cm/s). The resistance index of orbital blood flow decreased in all three vessels. After sublingual administration of 10 mg nifedipine, peak systolic blood flow velocity was slightly higher in the ciliary arteries and in the ophthalmic artery (before: Vsystolic 34.7 +/- 4.6 cm/s, after: Vsystolic 37.8 +/- 3.6 cm/s). Blood-flow velocity in the central retinal vein was elevated as well (before: Vmax 3.81 +/- 0.66 cm/s, after: Vmax 4.66 +/- 0.83 cm/s). Those slightly divergent results may be due to the different pharmacological spectrum of the two drugs investigated While nitroglycerin leads to dilatation of venous vessels, nifedipine acts primarily on small arteries. As nifedipine and other calcium channel blockers have been tested in patients with low-tension glaucoma, future color Doppler studies of such a population seem to be promising. PMID- 7780283 TI - [Coronal incision as the surgical approach to the orbits]. AB - The coronal incision of the skin extends from the ipsilateral preauricular region to the other side parallel to the coronal suture. The skin flap can then be mobilized down to nearly the floor of the orbits. We routinely use this incision in the following diseases and surgical procedures of the orbit: (1) osteo- and orbitotomies in premature synostosis of skull bones and craniofacial dysplasias; (2) frontobasal midface traumatology involving the orbit; (3) removal of fronto ethmoidal mucoceles and tumors with orbital involvement; (4) bilateral medial three-wall and lateral one-wall decompression in Graves' disease; (5) removal of tumors from the upper and medial level of the orbit via a transperiostal incision or an extended supraorbital resection. The major advantages of the coronal incision are the excellent exposure of normal and pathological structures of the (peri-)orbital region and the highly satisfying late cosmetic results. PMID- 7780284 TI - [Rhegmatogenic retinal detachment]. PMID- 7780285 TI - Orthostatic intolerance and orthostatic tachycardia: a heterogeneous disorder. AB - A series of autonomic function tests were performed in eight patients who had orthostatic intolerance and orthostatic tachycardia (> 36 bpm). All eight had an abnormal tilt-table test (mean tachycardia 50 bpm compared with 22 +/- 7 bpm in 31 normal subjects). Plasma volume was low in four out of six patients. There was a subnormal response to the cold pressor test in three out of eight patients. Intravenous atropine-induced tachycardia was subnormal in two out of eight patients. A segmental or patchy anhidrosis was present in six out of eight patients. Pilocarpine (0.0625%) induced miosis (three out of six) and exaggerated Valsalva ratio (one out of eight) were observed. A follow-up of six patients, 8 17 years after the autonomic evaluation, showed spontaneous and complete improvement in two out of six, partial improvement in one out of six, and persistence of symptoms in three out of six patients. A repeat autonomic evaluation in two patients with persistent symptoms, 2 and 5 years after the initial assessment, showed mild progression of sympathetic and parasympathetic dysfunction. This syndrome appears characterized by orthostatic tachycardia, low plasma volume, lack of adrenergic supersensitivity, and sudomotor abnormalities. A longitudinal follow up demonstrates patients with and without recovery. The syndrome appears heterogeneous in terms of onset, clinical manifestations, laboratory studies and outcome. PMID- 7780286 TI - Variation of aortic blood velocity with age at rest and during exercise in normal subjects. AB - The effect of age on aortic blood velocity signal and its derived indices of left ventricular function namely peak velocity, stroke distance (the velocity-time integral) and minute distance (stroke distance x heart rate) was studied at rest and at maximal-tolerated supine exercise using a 2-mHz continuous-wave Doppler ultrasound applied via the suprasternal notch in 66 normal healthy volunteers. The peak velocity, stroke distance and the minute distance, both at rest and at maximal exercise decreased with advancing age by 1-1.1% per annum between the ages of 20 and 70 years. Accordingly a method for age-adjustment of the peak velocity, stroke and minute distances was introduced for clinical use in assessing individual subjects. These results indicate that age is an important variable affecting aortic blood velocity and its derived variables as non invasive measures of left ventricular function both at rest and with exercise. The relationship with age is an important consideration when assessing individual subjects. PMID- 7780287 TI - The effect of severe brainstem injury on heart rate and blood pressure oscillations. AB - To determine whether an intact brainstem is essential for the generation of neurogenically mediated fluctuations of R-R intervals and blood pressure, three patients with cerebellar lesions causing severe brainstem compression or death, one patient with a large pontine infarct and one patient with a pontine haemorrhage, were studied. Time-frequency maps (based on a modified Wigner distribution) were constructed from blood pressure and R-R interval signals in these patients with brainstem injury and were compared with maps of normal control subjects. Low frequency sympathetically mediated rhythms (0.01-0.12 Hz) in systolic and diastolic pressure remained detectable but attenuated in patients with brainstem injury whereas there was an almost complete loss of normal R-R intervals rhythmicity over 0.01 to 0.5 Hz range. These data suggest that fluctuations in R-R intervals require an intact brainstem, whereas low frequency approximately 0.06 +/- 0.02 Hz blood pressure rhythms may be preserved by spinal sympathetic circuitry. PMID- 7780288 TI - Smoking induced differences in autonomic responses in military pilot candidates. AB - The effects of smoking on autonomic function, the renin-angiotensin-aldosterone system, plasma catecholamine and 11-dehydro-thromboxane B2 values were studied in 37 young male military pilot candidates, 19 smokers and 18 non-smokers. There was a higher diastolic blood pressure at rest and higher systolic blood pressure after 5 min during the orthostatic test in smokers. Smokers also had higher diastolic blood pressure levels after exercise in the hand-grip test. Smokers had a lower Valsalva ratio and higher tachycardia ratio in the modified Valsalva manoeuvre, suggesting a degree of autonomic dysfunction. Plasma renin levels at rest and plasma noradrenaline levels after hand-grip test were significantly higher in smokers, implying increased sympathetic activity and enhanced activation of the renin-angiotensin system. Our findings indicate that smoking in fit young men increases sympathetic activity and changes physiological responses to autonomic tests. PMID- 7780289 TI - Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor. AB - The control of human forearm cutaneous vascular resistance was examined using a combination of laser Doppler perfusion measurement and continuous Finapres blood pressure measurement. Tests which provoke changes in blood flow via different control mechanisms (local and neural) were applied in a group of ten healthy subjects. The purpose was to select from them a suitable (i.e. statistically significant) group to apply in cases where a disease process is suspected of interfering with the control of the skin circulation. Deep inspiration, immersion of the feet in water at 15 degrees C (both eliciting sympathetic vasoconstrictor nerve activity) and arm dependency (eliciting the local veni-arteriolar response) produced statistically significant, symmetrical increases in cutaneous vascular resistance in both arms (p < 0.05, Wilcoxon's test for paired differences). Similarly, post-ischaemic reactive hyperaemia (mediated by local vasodilator mechanisms) and indirect heating of the body (eliciting increased sympathetic vasodilator nerve activity) resulted in significant decreases in cutaneous vascular resistance (p < 0.01). When deep inspiration was repeated from a vasodilated baseline after indirect heating, the increases in cutaneous vascular resistance were smaller than those obtained before heating. Isometric handgrip exercise failed to produce a significant change in contralateral cutaneous vascular resistance (p > 0.05). There were no differences between right and left arms for any test (p > 0.05). The successful tests were subjected to power analysis in order to predict likely patient sample sizes required to demonstrate altered responsiveness at sites of microcirculatory disturbance compared with normal skin. PMID- 7780290 TI - Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection. AB - Autonomic neuropathy has been reported in human immunodeficiency virus positive (HIV+) patients. Since alterations in cardiac innervation may determine QT interval prolongation, this interval was studied in a group of HIV+ subjects to evaluate if it is prolonged and to compare this measurement with other diagnostic tests for autonomic neuropathy. Fifty-seven HIV+ and 23 human immunodeficiency virus negative (HIV-) subjects were studied. Autonomic function was tested by noninvasive cardiovascular reflex tests, and the QT interval on the electrocardiogram was measured at rest, at maximum tachycardia during Valsalva manoeuvre, and afterwards at maximum bradycardia. QT intervals were corrected for heart rate according to Bazzett's formula (QTc). Autonomic neuropathy was found in 37 HIV+ subjects: 25 had moderate autonomic neuropathy (HIV+/mAN) and twelve had severe autonomic neuropathy (HIV+/sAN). The 23 HIV- and 20 HIV+ (HIV+/AN-) patients did not have autonomic neuropathy. QTc intervals were significantly longer in HIV+/sAN and HIV+/mAN than in HIV- at rest; in HIV+/sAN than in HIV- at maximum tachycardia; in HIV+/sAN and HIV+/mAN than in HIV+, in HIV+/sAN and HIV+/mAN than in HIV+/AN- and in HIV+/sAN than in HIV+/mAN at maximum bradycardia. QTc was > or = 440 ms in 24 out of 37 (64.8%) patients with autonomic neuropathy and in five out of 20 (25%) HIV+/AN- patients (sensitivity 65%, specificity 75%). A significant correlation was observed between scores of autonomic involvement and QTc interval prolongation. This study confirms that the QTc measurement is a reliable parameter indicating the presence of autonomic neuropathy. Since QT prolongation may determine ventricular arrhythmias, such patients must be followed because they may be at increased risk of sudden death. PMID- 7780291 TI - The effect of graded calcium infusions on rhythmic blood pressure oscillations in normal man. AB - This study was designed to determine whether calcium contributes to the regulation of rhythmic oscillations in blood pressure. Six normal subjects received sequential 1-h infusions of calcium gluconate (1.5, 3.0 and 4.5 mg calcium/kg/h) during continuous blood pressure (Finapres) monitoring. The plasma ionized calcium ([Ca2+]) concentration increased from 4.6 +/- 0.07 mg/dl to 5.97 +/- 0.20 mg/dl (p < 0.01) with infusion. The mid-frequency (0.07-0.14 Hz, Mayer wave) power spectrum of diastolic blood pressure was depressed slightly following the first dose but increased significantly following the final dose (p < 0.05). The high-frequency (0.15-0.40 Hz) power spectrum of systolic blood pressure decreased following the first dose (p < 0.05) and subsequently remained low. The low-frequency (0.02-0.6 Hz) power spectrum was not affected. These results demonstrate that graded hypercalcaemia affects blood pressure oscillations in man. Our data suggest that the amplitude of the Mayer wave, a clinical marker of sympathetic vascular tone, is modulated in part by calcium. PMID- 7780292 TI - Muscle sympathetic nerve activity during postural change in healthy young and older adults. AB - Recent evidence suggests that during orthostatic stress the reflex increase in muscle sympathetic nerve activity may be diminished in older adults. To test this hypothesis, we measured muscle sympathetic nerve activity, plasma noradrenaline concentrations, heart rate, and arterial blood pressure in twelve young (mean, 25 years; range, 19-29 years) adults and 14 older (mean 64 years; range, 60-74 years) healthy adults, while supine and during upright sitting. Supine control levels of muscle sympathetic nerve activity were higher in the older subjects (35 +/- 1 vs. 25 +/- 1 bursts/min, p < 0.05), but there were no differences in plasma noradrenaline concentrations, heart rate or arterial pressure. Despite higher supine control levels in the older group, the absolute unit increases in muscle sympathetic nerve activity in response to upright sitting (p < 0.05 vs. control) were not different in the two groups (7 +/- 1 vs. 7 +/- 1 bursts/min), nor were the increases in plasma noradrenaline concentrations. Heart rate did not increase above supine control in response to sitting in either group. Arterial pressure increased slightly (p < 0.05, supine vs. control), but there were no age-related differences. These results indicate that, contrary to recent findings, the reflex increases in muscle sympathetic nerve activity and plasma noradrenaline concentrations and regulation of arterial pressure during this natural orthostatic stress are well preserved in older healthy men and women. PMID- 7780293 TI - Clinical significance of the resting heart rate in the assessment of autonomic function by cardiovascular reflex tests. AB - The effect of the resting heart rate on heart rate responses in standard cardiovascular autonomic function tests was studied in a sample of 845 subjects. The responses, which were calculated using instantaneous heart rate changes and R R interval ratios, were divided into quantiles according to their absolute values. The effect of resting heart rate on each cardiovascular index was studied by linear regression analysis, first in the whole group and then in the group with responses belonging to the lowest quantile. As regards the whole group, eight out of ten indices diminished significantly with increasing resting heart rate. However, no response-attenuating effect of increasing resting heart rate could be found among the responses in the lowest quantile. Since particularly low heart rate responses in cardiovascular reflex testing are of clinical importance when autonomic neuropathy is diagnosed, it can be concluded that the usefulness of standard cardiovascular reflex test based on heart rate changes is not limited by the level of the resting heart rate. PMID- 7780294 TI - Impulsiveness and subjective effects of intravenous cocaine administration in the laboratory. AB - Cardiovascular and subjective responses to placebo and 40-mg intravenous (iv) cocaine injections were measured in 29 male iv cocaine users: most subjects received each of these injections on two separate occasions. Most of the subjects also completed various measures of psychopathology and personality. Although the small sample size made any conclusions tentative, an expected significant association between impulsivity and subjective euphoria following 40-mg cocaine administration was obtained, whereas associations of personality measures with cardiovascular responses to cocaine administration were inconsistent. PMID- 7780295 TI - Determinants of early alcohol and drug use among young women in alcoholism treatment. AB - Substance abuse experimentation may be one of several types of problem behaviors. Data from 99 Caucasian women interviewed in alcoholism treatment (19-29 years old) were used to test a developmental model of substance experimentation. Respondents were classified into three groups based on their use prior to age 15: nonusers, users of alcohol only, and users of alcohol and other drugs. Family history of alcoholism was not related to childhood anxiety and impulse control problems. Childhood anxiety and impulse control problems predicted adolescent emotional and impulse control problems but did not differentiate early experimenters. Whereas adolescent emotional problems were not related to early experimentation, early drug and alcohol users were significantly more likely to have engaged in other impulsive behaviors (e.g., running away from home, trouble with school authorities) than were nonusers or users of alcohol only. Alcoholism prevention programs, therefore, would do well to target youth who exhibit acting out behaviors as a high-risk group for early alcohol and drug use. PMID- 7780296 TI - A study of the gender differences in morbidity among individuals diagnosed with alcohol abuse and/or dependence. AB - The majority of studies on medical consequences of excessive alcohol consumption have been carried out with male subjects, mostly from clinical or hospitalized samples. The purpose of this report was to study differences in morbidity outcomes of men and women among respondents diagnosed with alcohol abuse and/or dependence. Utilizing data from the 1988 National Health Interview Survey, this study compared several indicators of physical morbidity among male and female respondents meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987) alcohol abuse and/or dependence. The results revealed complex gender differences, not all of which can be explained by differences in sociodemographic characteristics or drinking practices. Moreover, the results indicated that it is inadequate to generalize results based on morbidity data of men with alcohol abuse and/or dependence to their female counterparts or female drinkers. Implications of these findings are discussed. PMID- 7780297 TI - Node-link mapping for counseling cocaine users in methadone treatment. AB - Treatment engagement problems associated with cocaine-using opioid addicts were addressed using a cognitively enhanced counseling strategy. Analysis of client urines, participation, and counselor ratings of clients over a 6-month period during treatment indicated that the use of node-link mapping--a multipurpose visual representation strategy for communication--produced better results for both low and high cocaine-using opioid addicts in methadone maintenance than those treated without this enhancement. PMID- 7780299 TI - Total body water adjustment of mean alcohol intakes. AB - Total body water volume (TBW) is one factor that determines the functional effect of a standard dose of alcohol. Because women and the elderly generally have lower TBW values than men and younger persons, respectively, less alcohol needs to be consumed by women and elders to achieve the same or higher blood alcohol levels compared to men and younger persons. An existing data set on elderly drinkers was analyzed with and without TBW adjustment of intakes using mean TBW estimates per decade for each gender. The estimates were obtained from a published report that pooled cross-sectional data to produce mean TBW values and TBW prediction equations applicable to Western populations. As the analyses confirm, the use of cutoff points of alcohol intake not adjusted for TBW results in drinking-level misclassification and findings biased towards younger males. This report supports the standard use of TBW-adjusted alcohol intakes in analyses of samples with both genders and/or a wide age range. PMID- 7780298 TI - Caffeinated coffee and tea intake and its relationship to cigarette smoking: an analysis of the Second National Health and Nutrition Examination Survey (NHANES II). AB - Recent studies have shown that smokers' intake of caffeine is higher than nonsmokers. This investigation evaluated the relationships between smoking status and self-reported caffeine intake from both coffee and tea. Subjects were adults who participated in the Second National Health and Nutrition Examination Survey (NHANES II). Results indicated that subjects who ingested caffeine from tea were more likely to be female, less educated, younger, non-Caucasian, and lighter drinkers. In contrast, those who ingested caffeine from coffee were more likely to be older, Caucasian, heavier drinkers, and have higher incomes. Smokers were not more likely to drink caffeinated tea. In contrast, smokers were much more likely to drink caffeinated coffee, and a dose-response relationship between caffeine from coffee and smoking intake was observed. These results clarify the relationship between smoking and caffeine intake. Implications for intervention efforts are discussed. PMID- 7780300 TI - A computer-directed program for smoking cessation treatment. AB - This report describes a computer-directed cigarette smoking cessation program that individualizes nicotine fading schedules for smokers based upon their daily smoking behavior. Previous outcome data from minimal intervention and intensive stop-smoking treatment studies are presented. Preliminary urinary cotinine data also are presented to validate the program's underlying assumption that computer directed nicotine fading results in across-treatment reductions in biological levels of nicotine. PMID- 7780301 TI - Gender differences in prospectively versus retrospectively assessed smoking withdrawal symptoms. AB - Investigations of gender differences in the frequency and/or intensity of smoking withdrawal symptomatology have yielded conflicting findings. Several studies using measures collected both before abstinence and at the peak of symptomatology have failed to find gender differences. Yet, when asked to rate symptomatology experienced during past quit attempts, women have repeatedly been shown to endorse significantly more symptomatology than men. A possible explanation is that, although men and women show no differences when rating symptoms prospectively, women remember their past withdrawal symptoms as being more severe than do men, either because women exaggerate the difficulties they experience or because men downplay them. To test this hypothesis, and to determine whether men or women were more accurate in their recollections, we combined data from two studies in which subjects were asked to assess symptoms prospectively following 2 days of abstinence, and also to rate withdrawal during past quit attempts. As predicted, we found the effects of abstinence to be similar when assessed prospectively but different when assessed retrospectively, with women reporting more symptomatology than men. Men whose retrospective and prospective responses were discordant consistently underestimated the likelihood of experiencing symptomatology; women showed no consistent trends. The total number of symptoms reported retrospectively by women was similar to the total number reported prospectively, whereas men significantly underestimated the number of symptoms that they actually experienced. These findings may suggest ways in which treatment strategies can be tailored to the differences between male and female styles in recalling past experiences with abstinence from smoking. PMID- 7780302 TI - Case management of pregnant and parenting female crack and polydrug abusers. AB - The increasing use of crack-cocaine among addicted women and subsequent births of polydrug-exposed infants prompted the State of Florida to undertake initiatives to seek solutions to these problems. This study, focused on one of these initiatives, explored the relationship between service components of a comprehensive treatment program and substance-free time among 120 African American and Caucasian crack-cocaine addicted women. Findings from a multiple regression analysis indicated that aftercare management (p < .0001), vocational services (p < .02), and residential treatment (p < .03) were statistically significant services associated with substance-free time. Although these findings are not conclusive, they are supportive of a growing body of literature that suggests that crack-using and polydrug-using women can be responsive to treatment when it is tailored to their individual needs and includes long-term community support. PMID- 7780303 TI - Circulatory response of young adult trauma victims with alcohol intoxication. AB - Young adults are a subgroup particularly susceptible to traumatic injury; alcohol intoxication is a major risk factor for trauma in young adults. During the first hours following multiple trauma, however, little is known about the specific effects of alcohol intoxication on the circulatory response of critically injured young adults. The purpose of this prospective study was to compare the circulatory response of 5 severely injured young adults (15-40 years old) with acute alcohol intoxication to the circulatory response of 5 severely injured, nonintoxicated young adults. Data were collected every hour for the first 8 hours after admission to a surgical intensive care unit. Subjects with alcohol intoxication had significantly higher heart rates (t = 2.8176, p < .05) than their nonintoxicated counterparts. Heart rate and blood pressure, however, showed no statistically significant (p < .05) Group x Time interaction between the two groups. Subjects with alcohol intoxication also had injuries that caused more blood loss, more invasive monitoring, more operative procedures, more fluid replacement, and higher oxygen requirements. PMID- 7780304 TI - Functional interaction between the homeotic genes fbp1 and pMADS1 during petunia floral organogenesis. AB - The petunia MADS box floral binding protein (fbp) gene 1 represents a class B homeotic gene determining the identity of second and third floral whorl organs. Suppression of fbp1, which is highly homologous to the Antirrhinum gene globosa and Arabidopsis gene pistillata, results in the conversion of petals to sepals and stamens to carpels. In contrast to fbp1, the petunia homeotic gene pMADS1, encoding a protein homologous to the Antirrhinum protein DEFICIENS, has been shown to be involved in the formation of petals only. We demonstrated that the induction of fbp1 is established independent of pMADS1, whereas at later developmental stages, fbp1 is up-regulated by pMADS1 in petals. On the other hand, the induction and maintenance of pMADS1 expression are not affected by fbp1. To obtain information about the functional interaction between fbp1 and pMADS1, an fbp1 cosuppression mutant with mild phenotypic alterations was crossed with a green petals mutant in which pMADS1 expression was abolished. Progeny plants, heterozygous for the pMADS1 gene, had flowers with a more pronounced reversion from petals into sepals than was observed for the parent fbp1 mutant. The morphology of the third whorl organs was not changed. These observations, together with expression levels of pMADS1 and fbp1 in mutant flowers, provide evidence for functional control of fbp1 by PMADS1 in vivo. PMID- 7780305 TI - Expression of the Arabidopsis HMG2 gene, encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, is restricted to meristematic and floral tissues. AB - The synthesis of mevalonate, which is considered the first rate-limiting step in isoprenoid biosynthesis, is catalyzed by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34). In Arabidopsis, HMGR is encoded by two differentially expressed genes (HMG1 and HMG2). The transcriptional activity of the HMG2 gene was studied after fusing different regions of its 5' flanking region to the beta-glucuronidase (GUS) reporter gene and transforming the resulting constructs into tobacco plants. The spatial and temporal expression directed by the HMG2 promoter in the transgenic plants is consistent with the expression pattern previously established by RNA analysis using an HMG2-specific probe. HMG2 expression is restricted to meristematic (root tip and shoot apex) and floral (secretory zone of the stigma, mature pollen grains, gynoecium vascular tissue, and fertilized ovules) tissues. Deletion analysis of the HMG2 5' flanking region was conducted in transgenic plants and transfected protoplasts. The region containing nucleotides -857 to +64 of the HMG2 gene was sufficient to confer high levels of expression in both floral and meristematic tissues, although deletion to nucleotide -503 resulted in almost complete loss of expression. Sequences contained within the 5' transcribed, untranslated region are also important for gene expression. The biological significance of the restricted pattern of expression of HMG2 is also discussed. PMID- 7780306 TI - UFO: an Arabidopsis gene involved in both floral meristem and floral organ development. AB - We describe the role of the UNUSUAL FLORAL ORGANS (UFO) gene in Arabidopsis floral development based on a genetic and molecular characterization of the phenotypes of nine ufo alleles. UFO is required for the proper identity of the floral meristem and acts in three different aspects of the process that distinguishes flowers from shoots. UFO is involved in establishing the whorled pattern of floral organs, controlling the determinacy of the floral meristem, and activating the APETALA3 and PISTILLATA genes required for petal and stamen identity. In many respects, UFO acts in a manner similar to LEAFY, but the ufo mutant phenotype also suggests an additional role for UFO in defining boundaries within the floral primordia or controlling cell proliferation during floral organ growth. Finally, genetic interactions that prevent flower formation and lead to the generation of filamentous structures implicate UFO as a member of a new, large, and diverse class of genes in Arabidopsis necessary for flower formation. PMID- 7780307 TI - Long-distance movement factor: a transport function of the potyvirus helper component proteinase. AB - Transport of viruses from cell to cell in plants typically involves one or more viral proteins that supply dedicated movement functions. Transport from leaf to leaf through phloem, or long-distance transport, is a poorly understood process with requirements differing from those of cell-to-cell movement. Through genetic analysis of tobacco etch virus (TEV; potyvirus group), a novel long-distance movement factor was identified that facilitates vascular-associated movement in tobacco. A mutation in the central region of the helper component proteinase (HC Pro), a TEV-encoded protein with previously described activities in aphid mediated transmission and polyprotein processing, inactivated long-distance movement. This mutant virus exhibited only minor defects in genome amplification and cell-to-cell movement functions. In situ histochemical analysis revealed that the mutant was capable of infecting mesophyll, bundle sheath, and phloem cells within inoculated leaves, suggesting that the long-distance movement block was associated with entry into or exit from sieve elements. The long-distance movement defect was specifically complemented by HC-Pro supplied in trans by a transgenic host. The data indicate that HC-Pro functions in one or more steps unique to long-distance transport. PMID- 7780308 TI - Small cysteine-rich antifungal proteins from radish: their role in host defense. AB - Radish seeds have previously been shown to contain two homologous, 5-kD cysteine rich proteins designated Raphanus sativus-antifungal protein 1 (Rs-AFP1) and Rs AFP2, both of which exhibit potent antifungal activity in vitro. We now demonstrate that these proteins are located in the cell wall and occur predominantly in the outer cell layers lining different seed organs. Moreover, Rs AFPs are preferentially released during seed germination after disruption of the seed coat. The amount of released proteins is sufficient to create a microenvironment around the seed in which fungal growth is suppressed. Both the cDNAs and the intron-containing genomic regions encoding the Rs-AFP preproteins were cloned. Transcripts (0.55 kb) hybridizing with an Rs-AFP1 cDNA-derived probe were present in near-mature and mature seeds. Such transcripts as well as the corresponding proteins were barely detectable in healthy uninfected leaves but accumulated systemically at high levels after localized fungal infection. The induced leaf proteins (designated Rs-AFP3 and Rs-AFP4) were purified and shown to be homologous to seed Rs-AFPs and to exert similar antifungal activity in vitro. A chimeric Rs-AFP2 gene under the control of the constitutive cauliflower mosaic virus 35S promoter conferred enhanced resistance to the foliar pathogen Alternaria longipes in transgenic tobacco. The term "plant defensins" is proposed to denote these defense-related proteins. PMID- 7780309 TI - Post-transcriptional regulation of nitrate reductase by light is abolished by an N-terminal deletion. AB - Higher plant nitrate reductases (NRs) carry an N-terminal domain whose sequence is not conserved in NRs from other organisms. A gene composed of a full-length tobacco NR cDNA with an internal deletion of 168 bp in the 5' end fused to the cauliflower mosaic virus 35S promoter and appropriate termination signals was constructed and designated as delta NR. An NR-deficient mutant of Nicotiana plumbaginifolia was transformed with this delta NR gene. In transgenic plants expressing this construct, NR activity was restored and normal growth resulted. Apart from a higher thermosensitivity, no appreciable modification of the kinetic parameters of the enzyme was detectable. The post-transcriptional regulation of NR by light was abolished in delta NR transformants. Consequently, deregulated production of glutamine and asparagine was detected in delta NR transformants. The absence of in vitro delta NR activity modulation by ATP suggests the impairment of delta NR phosphorylation and thereby suppression of delta NR post translational regulation. These data imply that post-transcriptional control of NR expression is important for the flow of the nitrate assimilatory pathway. PMID- 7780310 TI - Two copper-responsive elements associated with the Chlamydomonas Cyc6 gene function as targets for transcriptional activators. AB - In Chlamydomonas reinhardtii, cytochrome c6 (cyt c6) is synthesized only under conditions of copper deficiency when plastocyanin cannot be synthesized. In previous work, the copper-responsive regulation of cyt c6 synthesis was demonstrated to occur by control of transcription, with no contribution from post transcriptional processes. To understand the mechanism underlying its regulation, the genomic DNA encoding cyt c6 (Cyc6) was analyzed for the presence of copper responsive elements. Sequences lying between positions -127 and -7 with respect to the start site of transcription were found to be sufficient to confer copper responsive expression on either a promoterless or a minimal beta-tubulin promoter driven (arylsulfatase-encoding) reporter gene. Analysis of this 120-bp fragment indicated that copper-responsive elements lie in two distinct regions (between 110 to -56 and -127 to -109). ATG fusions between copper-insensitive promoters and the coding plus 3' untranslated region of the Cyc6 gene resulted in the accumulation of cyt c6 in copper-supplemented medium; this confirms earlier studies indicating a lack of post-transcriptional control in this copper responsive pathway. In the context of a constitutive promoter (derived from the beta-tubulin gene), each region was found to function as an activator of transcription in copper-deficient cells, and the metal specificity of the response of reporter genes containing either one or both regions was identical to that of the endogenous Cyc6 gene. The copper-responsive synthesis of cyt c6 is thus attributed to these two 5' upstream sequences. PMID- 7780311 TI - Inactivation of a Synechocystis sp strain PCC 6803 gene with homology to conserved chloroplast open reading frame 184 increases the photosystem II-to photosystem I ratio. AB - A gene of the unicellular cyanobacterium Synechocystis sp strain PCC 6803 that is homologous to the conserved chloroplast open reading frame orf184 has been cloned and sequenced. The nucleotide sequence of the gene predicts a protein of 184 amino acids with a calculated molecular mass of 21.5 kD and two membrane-spanning regions. Amino acid sequence analysis showed 46 to 37% homology of the cyanobacterial orf184 with tobacco orf184, rice orf185, liverwort orf184, and Euglena gracilis orf206 sequences. Two orf184-specific mutants of Synechocystis sp PCC 6803 were constructed by insertion mutagenesis. Cells of mutants showed growth characteristics similar to those of the wild type. Their pigment composition was distinctly different from the wild type, as indicated by an increase in the phycocyanin-to-chlorophyll ratio. In addition, mutants also had a two- to threefold increase in photosynthetic electron transfer rates as well as in photosystem II-to-photosystem I ratio-a phenomenon hitherto not reported for mutants with altered photosynthetic characteristics. The observed alterations in the orf184-specific mutants provide strong evidence for a functional role of the orf184 gene product in photosynthetic processes. PMID- 7780312 TI - Alternative medicine and general practitioners. Opinions and behaviour. AB - OBJECTIVE: To describe general practitioners' opinions and behaviour regarding alternative medicine. DESIGN: Cross-sectional survey of a random sample of Ontario and Alberta general practitioners. SETTING: General practices in Ontario and Alberta. PARTICIPANTS: A questionnaire was mailed to 400 general practitioners. Of the 384 eligible physicians, 200 completed the questionnaire. MAIN OUTCOME MEASURES: Reported beliefs and practices concerning alternative medicine. RESULTS: Acupuncture, chiropractic, and hypnosis were considered most useful and reflexology, naturopathy, and homeopathy least useful. Results showed 56% of general practitioners believed that alternative medicine has ideas and methods from which conventional medicine could benefit, 54% referred to alternative practitioners, and 16% practised some form of alternative medicine. Province of practice, place of graduation, training in alternative approaches, number of alternative approaches perceived useful, and attitude toward alternative medicine were clearly related to referring to alternative practitioners. Sex, age, type of practice, training in alternative medicine, referring to alternative practitioners, number of alternative approaches perceived useful, and attitude toward alternative medicine were related to practicing alternative medicine. CONCLUSION: Although acceptance and integration of alternative medicine extend only to certain approaches, alternative medicine cannot be discounted in general practice. A study encompassing all Canadian provinces could help in planning medical education and developing policies to guide physician behaviour. PMID- 7780313 TI - New tuberculosis epidemic. Controversies in screening and preventive therapy. AB - The incidence of tuberculosis is increasing in many regions of Canada and the world. Accurate and current knowledge of screening and prevention is of utmost importance for family physicians caring for patients who might be at risk. This article presents guidelines on screening, skin testing, interpretation of results, and preventive therapy. PMID- 7780314 TI - Mantoux tests. Performing, interpreting, and acting upon them. AB - Interpreting and acting upon results of the tuberculin skin test (Mantoux test) can be confusing because the test is inherently ambiguous and published recommendations for investigation and prevention of tuberculosis are complex. This article presents a step-by-step guide to enable family physicians to make effective use of the Mantoux test. PMID- 7780316 TI - Clerkship rotation in rural family practice. AB - Every medical student at Memorial University of Newfoundland must do a rotation in rural family practice. This paper describes the organization of this clerkship learning experience and discusses its possible influence upon career choice. PMID- 7780315 TI - Tuberculosis in the 1990s. Issues for primary care physicians. AB - After declining for many years, tuberculosis rates have begun to level off in Canada. Groups at particularly high risk include aboriginal Canadians, immigrants from high-prevalence countries, HIV-infected people, and elderly men. If disease is suspected, appropriate investigations, including sputum tests for bacteriology and chest x-ray examinations, should be done. Response to treatment is excellent. Chemoprophylaxis is recommended for certain patients. Vaccination with BCG has a limited but important role, especially for aboriginal Canadians. PMID- 7780317 TI - Rural home care of a technology-dependent infant. AB - A multidisciplinary approach is necessary to prepare for home care of technology dependent infants. The environment must protect, support, and promote the physical, cognitive, and social growth and development of these infants. Parents and caregivers of technology-dependent infants should be taught cardiopulmonary resuscitation and should be helped to develop a plan for obtaining emergency medical assistance. PMID- 7780320 TI - Don't worry about the label. Diagnose underlying perpetuating factors in chronic fatigue syndrome. PMID- 7780319 TI - Promoting Canada's involvement in international health. PMID- 7780318 TI - Health care system awry in Hong Kong. PMID- 7780321 TI - Gatekeeping. Part 2: Who and how? PMID- 7780322 TI - Health of Canada's children. A family physician's view. PMID- 7780323 TI - Higher dose increases addiction potential. PMID- 7780324 TI - Should x-rays be taken? PMID- 7780325 TI - Hospital privileges and family physicians. PMID- 7780326 TI - Rural medicine needs help. PMID- 7780327 TI - Green medicine. Environmental impact of health care. PMID- 7780328 TI - Radiology rounds. Osteochondritis dissecans. PMID- 7780329 TI - Dermacase. Papular acrodermatitis of childhood. PMID- 7780330 TI - Which one of the following statements about the use of paracentesis in the management of ascites is true? PMID- 7780331 TI - Rural family medicine training in Canada. AB - OBJECTIVE: To examine the status of postgraduate family medicine training that occurs in rural family practice settings in Canada and to identify problems and how they are addressed. DESIGN: A retrospective questionnaire sent to all 18 Canadian family medicine training programs followed by a focus group discussion of results. SETTING: Canadian university family medicine training programs. PARTICIPANTS: Chairs or program directors of all 18 Canadian family medicine training programs and people attending a workshop at the Section of Teachers of Family Medicine annual meeting. MAIN OUTCOME MEASURES: Extent of training offered, educational models used, common problems for residents and teachers. RESULTS: Nine of 18 programs offer some family medicine training in a rural practice setting to some or all of their first-year family medicine residents, and 99 of 684 first-year family medicine residents did some training in a rural practice. All programs offer some training in a rural practice to some or all of the second-year residents, and 567 of 702 second-year residents did some training in a rural setting. In 12 of 18 programs, a rural family medicine block is compulsory. Education models for training for rural family practice vary widely. Isolation, accommodation, and supervision are common problems for rural family medicine residents. Isolation and faculty development are common problems for rural physician-teachers. Programs use various approaches to address these problems. CONCLUSIONS: The variety of postgraduate training models for rural family practice used in the 18 training programs reflects different regional health care needs and resources. There is no common rural family medicine curriculum. Networking through a rural physician-teachers group or a faculty of rural medicine could further the development of education for rural family practice. PMID- 7780333 TI - [Phenomenon of tumor growth stability in the host's body. New approach to growth and treatment of tumors]. AB - The impact of surgical treatment of Ehrlich's carcinoma on animals' survival was studied. Tumour removal on posttransplantation day 30 was shown to cause no increases in the longevity of the animals operated on as compared with those non operated on (mean longevity was 59.9 and 62.2 days, respectively). The death causes of the animals operated on were metastases and relapses. On day 7 after transplantation, cyclophosphanum therapy of Ehrlich's carcinoma failed to prolong the animals' life. While 24 hours after tumour transplantation the longevity increased from 61.8 to 93.4 days. No therapeutical effects were shown to be associated with the influence of humoral factors of the host body on tumor growth. It was shown that the lack of these humoral factors resulted in interrupting tumor growth. PMID- 7780332 TI - [Tumor markers CEA, CA 15-3, MCA, TPA, ferritin and PTH in the diagnosis and monitoring of primary breast cancer]. AB - Sera from 254 females were assayed for markers of tumor growth, such as cancer embryonal antigen (CEA), breast cancer-associated antigen (CA 15-3), mucinoid cancer antigen (MCA), ferritin, tissue polypeptide antigen (TPA), parathyroid hormone (PTH) by means of monoclonal antibody kits by using radioimmunoassay and enzyme immunoassay. Forty nine patients were diagnosed as having benign breast neoplasms, 171 patients were admitted to the clinic for primary breast cancer of varying severities, 34 patients without any breast abnormalities and somatic diseases comprised a control group. There was a close correlation between the higher levels of markers and the stage of a tumorous process. Various therapies induced decreases in the levels of the markers serve as an objective criterion for the efficiency of the latter. Steady increases in the mean concentrations of tumor markers in the intra- and post-therapeutical periods are indicative of an extremely poor prognosis in this group of patients. PMID- 7780334 TI - [Comparison of the effectiveness and toxicity of parenteral and oral vepesid in the treatment of disseminated breast cancer]. PMID- 7780336 TI - [Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients]. AB - The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencephalography and peripheral blood lymphocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencephalography, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lymphocytes. These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization. PMID- 7780335 TI - [Evaluation of the effectiveness of tamoxifen in malignant breast tumors: new approaches]. AB - It has been shown that 17 beta-estradiol stimulates the cycle of phospholipid conversion in the breast tumor cells. The action of tamoxifen on antiestrogen cells is not limited by weakening the stimulating effect of 17 beta-estradiol on the exchange of intracellular phospholipids, but gives rise to a more complicated pattern of changes: inhibited incorporation of 32-P-phosphatidylcholine (PC) and activated exchange of phosphoinositides (PI). The experimental findings of 53 breast tumors have indicated that in 47.2% of cases Tamoxifen alters the PC/PI ratio and causes its 2-fold increase. Such alterations have been found to be induced by the ability of Tamoxifen to suppress the activity of protein kinase C that regulates the synthesis of PC and PI. It is suggested that the revealed capacity of Tamoxifen to change the rate of intracellular phospholipid conversion might be used for evaluating the efficiency of this agent on malignant tumors. PMID- 7780338 TI - [Public health and military medicine during the Great Patriotic War, 1941-1945]. PMID- 7780337 TI - [Several aspects of broncho-angioplastic surgery in onco-pulmonology]. PMID- 7780340 TI - [Use of histocompatibility class I molecule peptides for in vivo induction of specific T-suppressors in allogenic systems and prolongation of mouse skin graft life]. AB - Six synthetic peptides were selected for the individual molecule H-2Kb of the major histocompatibility complex class 1. Optimum conditions were elaborated for the induction of specific suppressor T cells in vivo by peptide 6 (alpha 2 domain) in an intravenous dose of 33 micrograms to the tail vein or 100 micrograms to the orbital sinus, followed by testing the suppressor activity in inhibiting in vitro proliferation in the three-cell MLC in response to irradiated cells of the stimulator Kb (BL/6) in the absence of suppressed response to the foreign stimulator Kk (B10.BR). Out of 6 different peptides of the same molecule H-2Kb, suppressor T cells were induced effectively by peptides 2 (alpha 2 domain), 5 and 6 (alpha 2-domain), while the high efficiency of suppressors is realized by memory cells along with peptides 2. Under the same conditions, in vivo peptide immunization did not induce cytotoxic T lymphocytes at all. In contrast, CTL were specific in their high efficiency where memory cells were in vitro pretreated with stimulators of warmed BL/6 cells. Intravenous administration of peptide 6 to mice gave rise to prolongation of Kb (BL/6 or B10.MBR)-induced skin transplantation during the transfer from allogenic murine R101 and B10.AKM, respectively, but without the terms of skin prolongation at all with the stranger donors Kk (B10.BR) or Kd (DBA/2). PMID- 7780339 TI - [Reconstructive surgery and organ-sparing methods in the treatment of patients with laryngeal and oral cavity tumors]. AB - Some advances have been recently made to improve survival rates among patients with common advanced larynx and oropharyngeal cancer. In this connection, it is essential to improve the quality of such patients' life. A total 382 patients with Degrees III-IV laryngeal and oral cancers were followed up. New approaches to treating these patients by combining various radiation, chemoradiation and surgical treatments, as well wide application of various primary plastic surgeries have yielded good functional and cosmetic results in most patients. PMID- 7780341 TI - [Synthesis of arachidonic acid cascade eicosanoids in tumors of various histogenesis in mice]. AB - The investigation was undertaken to characterize the profile of arachidonic acid metabolites in different spontaneous and transplantable tumors in mice. The five metabolites via the cyclooxygenase pathway (PGE2, PGF2 alpha, PGD2, TxB2, 6-keto PGF1 alpha), as well as the three lipoxygenase products (5-HETE, 12-HETE, and 15 HETE) were monitored by thin layer chromatography and high performance liquid chromatography after "ex vivo" metabolism of exogenous [1-C14]-arachidonic acid by homogenates of tumor tissues. It was shown that all tumors had a unique profile of eicosanoids. The most cyclooxygenase activity along with the significant synthesis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was noted in lung tumors. The antitumor effect of indomethacin was directly related to the ability of tumors to produce PGE2. On the other hand, there were varying lipoxygenase activities in tumors. In some cases, the extremely high levels of 15 and 12-HETE synthesis in neoplastic tissue could indicate that there was a basic possibility of using lipoxygenase inhibitors for suppressing malignant tumors. PMID- 7780342 TI - [DNA ploidy of tumor cells in prognostication of the course of malignant neoformations]. AB - DNA flow cytometry (FCM) was used for the clinical prognosis in patients undergone surgical removal of a tumor. The relationship between the structure of the tumor cell population (ploidy) and the frequency, time of a relapse onset (recurrence, metastasis), and the survival length were analyzed. All the patients had presurgical treatment (chemo- and/or radiotherapy). The patients were followed up for 5 to 9 years after surgery. The groups under study included 177 cases of breast cancer, 81 cases of larynx cancer, and 62 cases of colon cancer. Among the patients, the onset of a relapse was earlier and occurred more frequently in cases of aneuploid tumors among the patients regardless of the tumor type. In patients with aneuploid tumors, the most unfavorable prognosis was inherent in the hyperdiploid and multiclonal ones. The probability of 5-year survival for patients with aneuploid tumors appeared to be 20-30% lower than that in cases of diploid ones. PMID- 7780343 TI - [Preoperative hypoxia-radiotherapy in multimodal treatment of patients with stage III colonic cancer]. AB - The paper analyzes the results of surgical and multimodality therapies for 237 patients with Stage III colonic cancer, which were divided into 3 groups. Group 1 included 119 patients undergone only surgical management, Group 2 comprised 43 who were additionally treated with intensive radiation (4 Gy daily for 5 days) and Group 3 consisted of 75 patients who were irradiated in the presence of overall hypoxia evoked by breathing a gaseous mixture containing 9% oxygen. A five-year follow-up has indicated that there are significantly higher survival rates among those who have received a multimodality therapy rather than those merely operated on (82 +/- 5 and 53 +/- 9%, respectively). A short-term gaseous hypoxia has been found to reduce the incidence of systemic radiation reactions in patients during preoperative radiation and to fail to lower the efficiency of multimodality therapy. PMID- 7780344 TI - [Indicators of the state and effectiveness of cancer control in Russia]. AB - The paper analyses mortality rates due to malignant neoplasms and resultant socioeconomic losses, the risk of having and dying of these diseases throughout the coming life, the average longevity among cancer patients. These summarized indicators are considered by the authors as criteria for planning, managing, and implementing anticancer measures in the community. PMID- 7780345 TI - [Basic characteristics of macrophage as an effector cell]. PMID- 7780346 TI - [Role of outdoor and indoor air pollution in the etiology of lung cancer]. AB - The results of a case-control study of lung cancer risk in female non-smokers in Moscow are presented in the paper. The increase in a risk of lung cancer was found to be associated with outdoor pollution, the closure of the residence to chemical industry and ferrous and non-ferrous smelters, environmental tobacco smoke from husbands and exposure to radon (Rn) at home. The relative risk of lung cancer (RR) for those living in high air polluted versus relatively pure areas was 2.6 (95% CI = 1.2-5.6). RR of lung cancer related to the closure of the residence to chemical industry and ferrous and non-ferrous smelters were 2.0 (95% CI = 1.0-3.9) and 1.75 (95% CI = 1.0-3.1). The analysis has shown that there is an increase in lung cancer risk in women whose husbands smoke, which is as high as 1.9 (95% CI = 1.3-2.9). Lung cancer risk is associated with levels of exposure to Rn in the dwellings: RR was 2.48 (95% CI = 1.4-4.3) for the Rn concentration of > 24.3 Bq/m3 versus < 13 Bq/m3. PMID- 7780347 TI - Meditation and hypertension. PMID- 7780348 TI - Parasite molecules in cerebral malaria. PMID- 7780349 TI - Balloon angioplasty of the femoro-popliteal segment: follow up results from southern India. AB - BACKGROUND: Disease of the femoral and popliteal arteries, though one of the commonest manifestations of atherosclerosis, is under-recognized because the morbidity it produces is less catastrophic than coronary or cerebrovascular arterial involvement. Percutaneous transluminal angioplasty is performed for femoro-popliteal lesions at different centres in India, but post-angioplasty follow up data are scarce. We present our results after femoro-popliteal balloon angioplasty in 140 lesions. METHODS: Between 1986 and 1993, 140 femoro-popliteal angioplasties were performed in 119 patients with symptomatic limb ischaemia. Seventy-one per cent of patients had claudication and the others also had tissue loss. Eighty-two per cent of the lesions were occlusions. The average length of the lesions was 10.7 cm. Conventional wire-balloon angioplasty was performed in 128 lesions; in 12 others, laser-assisted balloon angioplasty was performed using an Nd-YAG laser thermal probe. Patients were followed up at regular intervals for any recurrence of symptoms and for objective evidence of restenosis or re occlusion. RESULTS: Despite a technical success in 83% of the lesions, cumulative primary patency calculated by the life-table method showed a slow decline which plateaued at 40% after 36 months. Long occlusions and multifocal stenoses showed shorter cumulative patency following angioplasty (27 months and 5.8 months respectively). Extensive luminal irregularity due to post-angioplasty intimal flaps was reduced by using warm contrast for balloon dilatation in 16 patients. In 14 patients who had repeat angioplasty for restenosis, the secondary patency showed a satisfactory figure of 84% at 60 months. CONCLUSION: Percutaneous transluminal angioplasty is a satisfactory alternative to surgery in femoro popliteal stenotic or occlusive disease. Regular follow up of such patients is essential in the first three years because re-occlusion can occur. We found that patency remained fairly constant after 36 months. Repeated angioplasty can maintain patency in patients with restenosis. PMID- 7780351 TI - Magnesium levels in serum and erythrocytes of children from Kerala. AB - BACKGROUND: Magnesium is required in higher quantities, during the phase of rapid growth, in children. Its level in the ground water in Kerala is low. This can cause magnesium deficiency especially in children from the lower socio-economic groups who also suffer from nutritional insufficiency. METHODS: We compared the serum and erythrocyte magnesium levels of school children from high and low (agricultural labourers and fisherfolk) socio-economic groups. These levels were determined using atomic absorption spectrophotometry. Body mass indices and haemoglobin levels were used as indirect measures of nutritional status. RESULTS: Serum and erythrocyte magnesium levels were significantly lower in both boys and girls from low socio-economic groups who also had lower body mass indices. CONCLUSION: Nutritional insufficiency is prevalent in children from the low socio economic groups and is associated with low serum and erythrocyte magnesium levels. PMID- 7780350 TI - Infection rates in single- and double-lumen central venous catheters in critically ill patients. AB - BACKGROUND: Catheter-related sepsis is a well known complication in critically ill patients receiving total parenteral nutrition. Micro-organisms may travel from the skin puncture wound along the external surface of the catheter or from the hub through the lumen of the catheter, to be shed into the circulation causing bacteraemia and sepsis. The incidence of sepsis is said to be about three times greater with multiple-lumen catheters than with single-lumen catheters. METHODS: Fifty patients admitted to our intensive care unit were randomly assigned to have either a single-lumen (Group I, 25 patients) or double-lumen (Group II, 25 patients) hydromer-coated, polyurethane central venous catheters of the same gauge and length, placed through the infraclavicular subclavian approach using the Seldinger technique. A sterile dry gauze dressing at the skin puncture site was changed every day. Skin swabs were taken for semi-quantitative culture studies before catheter insertion and removal, from the proximal 3 cm (lying subcutaneously) and distal 5 cm of the catheter segments on removal of the catheter, and venous blood was drawn from a peripheral vein before removal of the catheter. RESULTS: The most common isolate was coagulase negative Staphylococcus. No significant difference was found between the two groups in the incidence of catheter-related infection and catheter-related sepsis. CONCLUSION: Double-lumen central venous catheters placed in critically ill patients do not cause more sepsis than single-lumen catheters. PMID- 7780352 TI - Paternal leucocyte immunotherapy for recurrent pregnancy loss. AB - The defective recognition of foetal alloantigens by the maternal immune system is associated with recurrent pregnancy failure and may be prevented by boosting the maternal immune response with paternal or third party leucocyte immunization. The mechanism by which this process achieves success is not known. Clinical trials on recurrent spontaneous abortion have shown an up to 70% successful pregnancy rate after immunotherapy but the importance of this is unclear because there have been success rates of between 29% and 76% even in the control population. These variations could be due to small sample sizes and heterogeneity in the populations studied as well as co-intervention by the placebo. This article reviews the state-of-the-art for immunotherapy and discusses its mechanism of action in the prevention of recurrent foetal loss. PMID- 7780353 TI - Rational drug use in developing countries. PMID- 7780354 TI - DRD2 Ser311/Cys311 polymorphism in schizophrenia. PMID- 7780355 TI - Living related liver transplantation. PMID- 7780356 TI - AIDS. PMID- 7780357 TI - Poliomyelitis in Indian adults. PMID- 7780358 TI - Medical Council of India and the General Medical Council, United Kingdom. PMID- 7780359 TI - Stress and medical practice. PMID- 7780360 TI - Cost analysis of blood surveys for the detection of microfilaria carriers in rural areas. PMID- 7780361 TI - HLA phenotypes in Asians developing tuberculosis on dialysis or after renal transplantation. PMID- 7780362 TI - Astropathy for cure. PMID- 7780363 TI - Medicine and the Indian media. PMID- 7780364 TI - Safe disposal of disposables. PMID- 7780365 TI - Fluoroquinolones should be used rationally. PMID- 7780366 TI - Responsible reporting on epidemics. PMID- 7780367 TI - Induction of ovulation and multiple pregnancies. PMID- 7780368 TI - [Molecular mechanisms of the toxic action of the mycotoxin zearalenone on phospholipid metabolism, peroxide formation processes in membranes of brain mitochondria and erythrocytes, resistance of the latter to peroxide hemolysis in white rats and effects of sodium thiosulfate under these conditions]. PMID- 7780369 TI - [Trophic effect of neurotransplants on suppression of seizure activity in rats with hereditary epilepsy]. PMID- 7780371 TI - [Features of the contractile reaction of the chick embryo amnion upon action of acetylcholine on its inner and outer surface]. PMID- 7780370 TI - [Dynamics of spontaneous contractions of an isolated cardiomyocyte in vitro]. PMID- 7780372 TI - [Embryogenesis of the olfactory bulb in cats]. PMID- 7780374 TI - [Survival and distribution of genetically engineered microorganisms in laboratory water microecosystems]. PMID- 7780373 TI - [Mediators of synaptic transmission in ganglia of the tracheal plexus]. PMID- 7780375 TI - Photolabeling of human serum albumin by 4-azido-2-([14C]-methylamino) trifluorobenzonitrile. A high-efficiency, long wavelength photolabel. AB - N-alkyl derivatives of perfluoroarylazides are excellent candidates for photolabeling of proteins since they have absorption spectra in the 340-350 nm range permitting photolabel absorption without direct protein photolysis. The [14C]-N-methylamino derivative of 4-azido-tetrafluorobenzonitrile has been used to demonstrate that 80% of the photo-induced nitrene transient becomes covalently attached to HSA during photolysis. Multiwavelength detection of the photoprobe protein separation by size exclusion chromatography is shown to be an effective tool for assessing the conjugation of the photoprobe to the protein. PMID- 7780376 TI - Synthesis and in vivo disposition studies of 18F-labeled HFA-134a. AB - A rapid synthesis of the chlorofluorocarbon replacement compound 1,1,1,2 tetrafluoroethane (HFA-134a) was identified and utilized to prepare 99+% radiochemically pure [18F]HFA-134a in 20-35% radiochemical yield. Four rats were then exposed to no-carrier-added (NCA) [18F]HFA-134a, and monitored via coincidence detection. Following withdrawal of the test atmosphere of [18F]HFA 134a, the mean half-life of [18F]HFA-134a in four rats was determined to be 7.8 +/- 1.5 min following a 10 s exposure and 8.1 +/- 1.7 minutes following a 10 min exposure. PMID- 7780377 TI - Prompt-gamma neutron activation facility for measuring body nitrogen in vivo in small animals. AB - We have designed a prompt-gamma neutron activation facility for in vivo measurements of total body N in small animals. The facility incorporates a 252C neutron source with an emission rate of 3.2 x 10(8) n s-1 (140 micrograms), and a heavy-water neutron collimator-moderator assembly, together providing an optimum thermal flux-to-dose ratio for a 0.25-0.5 kg animal. Using two NaI(Tl) detectors we can attain a fractional statistical error of measurement of 3.5% for a dose equivalent of approx 50 mSv, sufficiently low that serial measurements can be made on the same animal. PMID- 7780378 TI - Comparison of the psychometric characteristics of three quality of life measures in intractable epilepsy. AB - Understanding how epilepsy affects an individual's quality of life (QOL) requires reliable and valid QOL measures. Analyses of reliability and validity rarely examine measures obtained in the same sample, making comparisons among measures difficult. We report analyses of internal consistency reliability, face, content, construct and criterion validity for the Epilepsy Surgery Inventory-55 (ESI-55, a measure based on the SF-36 Health Survey), the Sickness Impact Profile (SIP) and the Washington Psychosocial Seizure Inventory (WPSI) administered concurrently in the same sample of intractable epilepsy patients. Results generally support the validity of all three measures in assessing the aspects of QOL they were designed to address. The ESI-55 and SIP assess a broad, multi-dimensional construct of QOL in epilepsy, compared with the more specific focus of the WPSI on psychological and social adjustment. Judged by objective psychometric criteria, the ESI-55 and SIP are preferred over the WPSI in studies of the broad impact of epilepsy on quality of life. PMID- 7780379 TI - Advances in methods for assessing the impact of epilepsy and antiepileptic drug therapy on patients' health-related quality of life. AB - We studied 31 previously validated and newly developed generic and epilepsy specific scales to evaluate their usefulness for assessing the impact of epilepsy and anti-epileptic drug (AED) therapy on health-related quality of life (HRQOL). Included were the MOS SF-36 Health Survey, additional measures of mental health, cognition, epilepsy-specific perception of control, behavioural problems, distress, worries and experiences, the Liverpool Epilepsy Impact and Seizure Severity scales, and a patient-completed symptom checklist. Questionnaires were completed twice by 136 patients on AED therapy in a multicentre study in the UK. Validity was assessed in relation to disease severity, defined as time since last seizure, and to patient-reported symptoms. Statistical analyses to estimate the contribution of HRQOL information of each scale relative to that of others were conducted. The 171-item questionnaire could be completed by out-patients with epilepsy with good data quality. With few exceptions, generic and epilepsy specific measures satisfied psychometric tests of hypothesized item groupings and scale score reliability (internal consistency and test-retest reliability) and differentiated well between groups of patients differing in time since last seizure and in symptom impact, regardless of time since last seizure. However, scales differed widely in their validity in discriminating between groups of patients known to differ clinically. The SF-36 Role Physical scale best discriminated among groups differing in disease severity. The epilepsy-specific Mastery, Impact, Experience, Worry, Distress, and Agitation scales were among the 10 best measures in discriminating among groups differing in disease severity. Generic measures, especially measures of social and role functioning and mental health, were best at differentiating groups of patients differing in symptom impact. Recommendations are offered for concepts and specific scales most likely to be useful in future studies of the HRQOL burden of epilepsy and the HRQOL benefits of AED therapy. PMID- 7780380 TI - The Q-TWiST approach to assessing health-related quality of life in epilepsy. AB - We propose to develop a methodology for evaluating clinical interventions for epilepsy in terms of their effects on disease-related outcomes, social cost and quality of life, while incorporating patient preference. The technique represents an extension of the 'quality-adjusted time without symptoms and toxicities' (Q TWiST) method, which has been previously used to evaluate treatments for cancer and AIDS with respect to their costs in terms of toxicities, and benefits in terms of improved progression-free and overall survival. The extensions we propose to develop allow additional dimensions of quality of life relevant to epilepsy to be included in the analysis. We demonstrate a possible application of the proposed Q-TWiST method with a hypothetical example comparing surgery vs antiepileptic medication management alone for seizure control. The trade-offs between these alternative treatments are highlighted, along with patient importance weightings regarding various dimensions of quality of life. We describe further research needed to develop the methodology fully and comment on its potential usefulness. PMID- 7780381 TI - The contribution of the measurement of seizure severity to quality of life research. PMID- 7780382 TI - Agreement between self reports and proxy reports of quality of life in epilepsy patients. AB - Agreement between self reports and proxy reports of quality of life was examined in a sample of 292 patients with epilepsy and their designated proxies. Patients and proxies completed an 89-item Quality of Life Inventory (QOLIE-89), with the items rephrased for the proxy. Results reveal moderate correlations (product moment r ranging from 0.29 to 0.56 for 17 multi-item scales) between self reports and proxy reports. Agreement was good for measures of function that are directly observable and relatively poor for more subjective measures. Mean scale scores were significantly different between patients and proxies for only five of 17 multi-item scales. Proxy respondents systematically reported better functioning than did patients in three scales assessing cognitive functioning (all p < 0.001). By contrast, patients reported more positive health perceptions and less seizure distress than proxies. Patient educational attainment correlated inversely with degree of disagreement between patient and proxy reports for six of the 17 QOL scales and for the overall score. In addition, proxy educational attainment correlated positively with agreement for four scales. This study indicates that for group level comparisons, proxy respondents can be substituted for adults with epilepsy having low to moderate seizure frequency. However, for individual level assessments proxies should be used with caution. PMID- 7780384 TI - Directions for future research. Health related quality of life in epilepsy. PMID- 7780383 TI - The routine use of health-related quality of life measures in the care of patients with epilepsy: rationale and research agenda. AB - Reliable and valid patient-completed questionnaires to assess the health related quality of life (HRQOL) of people with epilepsy are becoming increasingly available. At present, however, they are not routinely used in epilepsy patients' care. The use of HRQOL measurement in clinical practice settings may improve the quality of care for people with epilepsy through (1) increasing the detection of patients' problems with daily functioning and well-being: (2) guiding therapeutic management; and (3) leading to improvements in patients' HRQOL and satisfaction with care. To realize the potential benefits of HRQOL assessment in the care of people with epilepsy, research into the feasibility of the office-based use of HRQOL questionnaires, measurement quality, and the impact of routine HRQOL assessment on the quality of epilepsy patients' care needs to be undertaken. The transfer of HRQOL questionnaires from research tools into clinical tools requires the collaboration of social scientists, health services researchers, and clinicians. HRQOL questionnaires have the potential to become a new clinical tool which could enhance the quality of care physicians are able to provide for their patients with epilepsy. PMID- 7780385 TI - Advances in the measurement of health-related quality of life in epilepsy. PMID- 7780386 TI - The evolution of health-related quality of life assessment in epilepsy. AB - The purpose of this article is to review the ways in which quality of life has been assessed in patients with epilepsy. It is specifically proposed that there have been three phases or types of studies examining the effects of epilepsy on cognitive, behavioural, social and physical function. The first and oldest phase was characterized by the use of traditional forms of clinical evaluation and available generic measures of cognitive, behavioural and psychosocial function to study the general effects of epilepsy, effects of epilepsy-specific clinical variables (e.g. seizure type, age at onset), and the consequences of treatment with antiepileptic medications on patients' lives. The second phase of research was characterized by the development of epilepsy-specific measures of cognitive ability, psychological status and psychosocial status, which were designed to meet the special research and clinical needs not provided by previous generic measures (e.g. Washington Psychosocial Seizure Inventory, Fear of Seizures Scale). The third and most recent phase is characterized by the use of models, techniques, and measures developed from the health services research field to assess formally contemporary definitions of health-related quality of life (HRQOL) (e.g. ESI-55, QOLIE-89, Seizure Severity Scale) and develop models of the effects of epilepsy on HRQOL. Thus, concern regarding the impact and consequences of epilepsy is not a new development, but has evolved over the years, resulting in new models and methods of assessment of disease impact on well-being and functional status. PMID- 7780387 TI - Flap coverage of a chronic hallux ulcer. AB - For nonhealing, noninfected plantar ulcerations of toes, flap coverage can be a viable alternative, providing there is adequate vascular supply to the digit. This article presents an interesting case, wherein the digital ulcer was covered with a flap from the same toe. The flapped area was then covered with a skin graft. PMID- 7780388 TI - The role of endoscopy in treatment of stenosing posterior tibial tenosynovitis. AB - Some foot and ankle pathologic conditions can be treated by an endoscopic approach. Its effectiveness has been reported in the treatment of plantar fasciitis. The authors have used an endoscopic approach in the treatment of posterior tibial tenosynovitis resistant to nonsurgical treatment. A review of the pathology, terminology and the diagnosis of tenosynovitis is provided. The case report demonstrates a technique using an endoscope to incise the posterior tibial tendon sheath. PMID- 7780389 TI - Protocol for lower extremity trauma. AB - Trauma to the lower extremity has been treated in the past by many specialties and subspecialties of medicine. No specialty, however, should be better qualified or trained in treating lower extremity trauma than the podiatrist. This study reviews some critical principles of acute trauma management and treatment. A simple algorithm is suggested. Three representative case studies are presented, demonstrating the importance and value of an established protocol. PMID- 7780390 TI - Elective foot and ankle surgery in the diabetic patient. AB - The philosophy of treating diabetic foot pathology has changed dramatically throughout the years. No longer are old, unfounded fears considered the standard of care. The authors enumerate on their indications and goals of treating this complex entity. Clinical aids, as well as patient evaluations are discussed. PMID- 7780391 TI - Forefoot postoperative continuous pain control by nonelectronic device. AB - The authors present a system against postoperative pain in forefoot operations, which functions by continuous infusion of anesthetic in the malleolar internal space. The system (Single-Day Baxter Infusor) was utilized in 145 patients who had undergone forefoot surgery. The effectiveness of the method was evaluated by means of a numeric scale (0 to 5) reflecting pain level. The method was effective in controlling postoperative pain in 110 cases (score 0 to 1); 25 cases (score 2) reported pain in the dorsal hallux, in the deep peroneal area, whereas in 10 cases (score 4 to 5 on the scale), nonsteroidal anti-inflammatory drugs had to be administered. PMID- 7780392 TI - Ancient schwannoma of the foot. AB - Ancient neurilemoma (schwannoma) is an uncommon variant of neurilemoma. On the basis of histology, this slow-growing, benign neoplasm has often been confused with sarcoma, and this confusion has resulted in overzealous resection. The authors report a case of this lesion affecting the plantar aspect of the foot. A discussion of the clinical and histological findings that emphasizes diagnosis and treatment is included. PMID- 7780393 TI - Endoscopic heel anatomy: analysis of 200 fresh frozen specimens. AB - The authors radiographed and dissected 200 fresh frozen cadaveric specimens selected randomly from the general United States population. A 21% incidence of inferior calcaneal exostosis formation was identified. Of those specimens identified as having an inferior calcaneal exostosis, there was a 52.4% incidence of heel spurs that were in the plantar fascia and a 47.6% incidence of heel spurs that were identified superior to the plantar fascia. After dissection of the specimens, the mean width and thickness of the medial, central and lateral bands of the plantar fascia, and the width of the medial and lateral subcutaneous fat were calculated. The presence of an inferior calcaneal bursa was identified in one specimen, and the presence of a heel neuroma was identified in 0 specimens of the 200 examined. The results of this study will assist the practitioner in performing the endoscopic plantar fasciotomy by providing the surgeon with quantitative averages of fascial dimensions. By knowing these fascial measurements, the practitioner will be aided intraoperatively in determining what level of fasciotomy to perform. This could help obviate some of the postoperative biomechanical sequelae that can occur with total releases, and immediate postoperative excessive ambulation by the patient. This study may help to gain insight into the true etiology of heel spur syndrome/plantar fasciitis. PMID- 7780395 TI - Microbiology of osteomyelitis in diabetic foot infections. AB - The objective of this report is to describe the bacterial pathogens in diabetic patients with osteomyelitis due to neuropathic foot ulcerations. The authors reviewed the records of 36 diabetic patients with osteomyelitis of the foot due to neuropathic ulceration. Intraoperative deep soft tissue and bone specimens were obtained from each patient. The mean age of patients was 56.7 years, and the mean duration of diabetes was 14.9 years. Streptococcus species (61%) and Staphylococcus aureus (47%) were the most common organisms identified. Gram negative aerobes were found in 18 cultures (50%). Only five patients' cultures (14%) were identified with anaerobic pathogens. The average number of pathogens per patient was 2.25. The most common bacterial pathogens in bone infections in diabetics were Streptococcus species and Staphylococcus aureus. Anaerobes were uncommon. PMID- 7780394 TI - Ganglion cyst of the hallux: an aberrant presentation. AB - Ganglion cysts are benign, thin walled, fluid-filled lesions commonly occurring in the distal extremities. Although widely debated in the literature, a true, identifiable etiology has remained elusive. The authors report on a ganglion cyst with a unique presentation on the hallux, and a review of the literature. PMID- 7780396 TI - Evaluation of Wagdy's technique for treatment of hallux valgus by double-V osteotomy. AB - Seventy-nine feet in 71 patients with hallux valgus were treated by double-V Wagdy osteotomy of the first metatarsal head. Sixty-eight per cent were totally free of pain with acceptable cosmetic appearance. Excellent and good results were obtained in 97.5% of the cases. The mean postoperative decrease of the intermetatarsal angle was 1.8 degrees and of the hallux valgus angle 22 degrees. The operation is technically simple and stable without internal fixation. It restores the length of the hallux and reduces the possible complications of nonunion, avascular necrosis, shortening of the first metatarsal, and appearance of new bone formation at the medial aspect of the osteotomy site. PMID- 7780397 TI - Identification and treatment of the diabetic neuropathic foot. AB - The authors discuss neuropathic osteoarthropathy in the diabetic foot, often associated with Charcot joints. Identification of this malady as well as indications for treatment are reviewed. Representative cases are illustrated. PMID- 7780398 TI - Enchondroma of the proximal phalanx. AB - Enchondromas are the most commonly seen benign tumors of the small bones of the foot. If symptomatic, these tumors often require surgical excision. Foot surgeons must weigh the surgical alternatives with respect to relief of symptoms, prognosis, cosmesis, and function. The authors present a typical case presentation of a solitary enchondroma in a phalanx. PMID- 7780399 TI - Biodegradable internal fixation. AB - The objective of this article was to assess the value of the use of biodegradable materials in internal fracture fixation according to the current literature. Research methods included a computerized Medline search and a hand check of references of identified articles. Also, a complete reference list was obtained from the manufacturer of Biofix (Bioscience Ltd., Tampere, Finland). The reviewers abstracted descriptive information about population, materials, complications, follow-up times in clinical trials and strength of fixation, complications, and population for animal experiments. Results indicated that sterile sinus formation is mostly associated with polyglycolic acid, with rates up to 25%, and to a lesser extent, polylactic acid. Volume of implanted material and vascularity of bone appeared to affect the rate of sinus formation. Absorbable fixation was equivalent to or better than steel fixation for functional outcome refracture rate, and in transepiphyseal femoral and humoral fractures. Polyglycolic acid and polylactic acid both became toxic between 10 days and 4 weeks of hydrolysis. Polyglycolic acid had the highest initial strength at 370 MPa compared with other polymers. PMID- 7780400 TI - A simplified technique for bending Kirschner wires. AB - Kirschner wires are extremely popular in foot surgery for fixation of osteotomies and digital procedures. Bending the protruding portion of a Kirschner wire used for fixation in foot surgery can sometimes be troublesome. A simplified technique is presented for bending protruding Kirschner wires using a Frazier size 3 suction tube. PMID- 7780401 TI - An unusual case of diabetic cellulitis due to Pasturella multocida. AB - Pasturella multocida is a well known potential cause of infection following bites or scratches by animals. The organism causes the usual clinical manifestations of a rapidly developing cellulitis at the site of injury. The resultant infection is dangerous and can progress on to a deep infection, osteomyelitis, and septicemia. In compromised patients, the source and etiology of the infection may be obscure making definitive diagnosis difficult. This paper reviews a very unusual case of a foot infection in a diabetic patient that was due to a domestic pet licking an excoriation on the foot. PMID- 7780402 TI - Subungual exostosis. AB - The author describes subungual exostoses as well as their differential diagnoses. Clinical and radiologic features are illustrated. Surgical excision is recommended, following partial toenail avulsion, in the majority of symptomatic cases. PMID- 7780403 TI - The barbarians are at the gate. PMID- 7780405 TI - Advanced perioperative nursing: selected physiological effects of trauma. AB - This article reviews selected physiological responses to trauma. These responses help the person to partly meet the challenge of the trauma by changing endocrine and metabolic functioning with the release of endogenous chemicals. PMID- 7780404 TI - Coordination and collaboration of violent trauma care. AB - The STC has the luxury of an all RN staff, capable of functioning in any of the surgical specialities. The PTN is a specialitist at being a generalist to provide care to a critically injured population. The role of the PTN is multifaceted and varied; it can be best described as functioning as a multidisciplinary coordinator and case manager in meeting the demands of the violent trauma patient. The patient often enters the OR severely injured, intubated, and incapable of self-protection or determination. The most important function of perioperative nursing is that of patient advocate. No other member of the trauma team is as focal to the patient's safety and comfort as the nurse. Passage from the scene of violent trauma to the OR requires dynamic assessment skills, critical thinking, and organizational capabilities. As long as interpersonal altercation results in intentional trauma, there will be a need for perioperative trauma nurses with the committement and expertise to mend the wounds of violent trauma victims. PMID- 7780406 TI - Notes from the field: interview with a perioperative trauma night nurse. Interview by Julie A. Meador. AB - Trauma has significantly impacted our operating rooms with increases in care costs, staffing, and procedural needs. This article presents an interview with a frontline player in perioperative trauma, a night perioperative care coordinator. The coordinator provides a look into what it is like to plan, coordinate, and give perioperative trauma care on the night shift of a level I trauma center. PMID- 7780407 TI - Blood products replacements processed in the surgical field. AB - This article summarizes the main blood products that can be gathered from, treated, and returned to the trauma patient in the operating room. A brief description of the physiology of blood and clotting mechanisms is given. A focus on plasma pheresis is provided, as well as a suggested procedure for plasma collection. PMID- 7780408 TI - Safety in intraoperative trauma care. AB - Care of patients with penetrating trauma is risky because of increased prevalence of blood borne disease. Perioperative nurses have constant exposure to body fluids so they are at an increased risk of exposure. Personal safety has emerged as one of the primary workplace concerns of nurses. This report reviews intraoperative safety, Association of Operating Room Nurses and Occupational Safety and Health Administration standards, and universal precautions in practice. PMID- 7780409 TI - Perioperative considerations of firearm injuries. AB - The trauma patient who presents to the operating room averages three to six separate surgical procedures initially. Almost half of all trauma is because of penetrating injuries and, more often than not, is the result of injury by firearms. Successful intervention during the perioperative phase is a result of critical thinking and planning by the perioperative nurse based on familiarity with the mechanism of injuries produced by firearms. An understanding of the types of weapons and ballistics will give the perioperative nurse a basis for assessment and care planning. PMID- 7780410 TI - Pharmacological resuscitation in trauma. AB - With every patient who is involved in a traumatic event, the potential for catastrophe is hanging over the heads of everyone on the initial care team. There is a need to develop protocols and routines to provide care during these high stress periods. This article discusses the role of team members in the care of the trauma patient. It is also important to have a quick overview of the medications used in the resuscitation of the patient. The article discusses pharmacological adjuncts to the resuscitation and management of the trauma patient. This review of cardioactive and supportive medications can provide a review of medications commonly used in the initial treatment of the trauma patient. Whether the patient experiences cardiac arrest or not the potential exists at any time treatment period for the problem to develop. Constant review of needed medications and protocols will assist in the management of the patient. PMID- 7780411 TI - Another routine case: gunshot trauma. AB - This case study describes the surgical repair of noncomplicated gunshot wounds in a young man. The preoperative assessment and surgical procedures, including bullet retrieval, is given. A systematic routine for handling emergency gunshot wound patients is shared as intraoperative nursing is described. Direct cost of this surgery to the operating room is explored. PMID- 7780412 TI - Selection of regional anesthesia for trauma. AB - The type of trauma, the desires of the patient, and the skills of the practitioner dictate the type of anesthesia for any surgical procedure. This article briefly reviews physiological and contiguous considerations of choosing and administering regional anesthesia technique for the trauma patient. Selected potential complicating factors present in the emergency trauma patient are also briefly discussed. PMID- 7780413 TI - Bullet retrieval in the operating room. AB - Valuable trace evidence is often lost or destroyed because of faulty collection and preservation techniques during surgical management of gunshot wounds. An experiment was conducted to show the importance of proper collection techniques and preservation of forensic evidence. Results are noted, a discussion is given, and a protocol for the surgical retrieval of bullets is presented. PMID- 7780414 TI - Positioning of infants and children for surgery. AB - The positioning of infants and children for surgical intervention must have the same goals and outcomes as that for adults, ie, no risk of nerve damage, adequate tissue perfusion without compromise of respirations, and optimal exposure for the surgical team. The difference between treating infants and children is in the positioning aids use, which are related to height and weight rather than age. PMID- 7780415 TI - Pediatric anesthesia. AB - Pediatric anesthesia differs from that of adults in many critical ways. Patients in the pediatric group are not required to fast for long periods before surgery. Induction of anesthesia is usually accomplished via inhalation agents. The pediatric airway and its anatomical differences are of special concern to the anesthesia provider and the postanesthesia nursing staff. PMID- 7780416 TI - The pain experience in infants, children, and adolescents. AB - Postoperative pain in adults has become a subject that has seen increasing research. The result of that research has been an increase in the type and quality of interventions available for pain relief. Although infants, children, and adolescents also experience postoperative pain, the research and interventions have been slower in arriving. Perhaps this is caused, in part, by the inability of this population to express the pain experience. It may also be because of the reluctance of health care providers to objectively assess and intervene in the pain experience of infants, children, and adolescents. The purpose of this article is to explore the pain experience of infants, children, and adolescents so the perioperative nurse will be better equipped to handle this experience with the patient and the family. PMID- 7780417 TI - Ross-Konno procedure: a case study of a newborn. AB - The objective is to present a case study of a 2-day-old infant who undergoes a Ross-Konno procedure for correction of severe congenital aortic stenosis. This procedure involves replacing the stenosed aortic valve with a pulmonary autograft. The perinatal history, diagnostic data, and the operative procedure are described. Preoperative and postoperative nursing management is addressed including normal pediatric intensive care protocols. The infant's postoperative hospital course was 37 days. Mitral regurgitation and pulmonary hypertension are being managed with lisinopril. PMID- 7780418 TI - Advanced practice case study: congenital hemangiomas. AB - Congenital hemangioma is the most common tumor of infancy. Usually it occurs singly in the skin. Occasionally multiple tumors are present and can involve other body organs. Congenital subglottic hemangioma is considered rare, but when it occurs can be life threatening. This article discusses the different options available for treatment of subglottic hemangioma and the course of treatment chosen for Baby S. taking into consideration her diagnosis, family situation, and the availability of an experimental drug therapy. PMID- 7780419 TI - Repair of a recto-vaginal fistula as a result of sexual assault. AB - A thorough and careful examination should always be performed for a child with a presenting complaint of sexual abuse. Rarely will a child suffer extensive injuries requiring surgical repair. This case study is of a 4-year-old girl who sustained severe penetrating trauma of the vagina and rectum resulting in a recto vaginal fistula. She presented 2 months after the assault and required anogenital reconstruction with a temporary colostomy. Initial and long-term surgical management of this case is discussed. PMID- 7780420 TI - Laparoscopy and thoracoscopy in infants and children. AB - The recent revolution in adult laparoscopic and thoracoscopic surgery is gaining momentum in the pediatric surgery arena. Pediatric general surgeons, urologists, and thoracic surgeons have all reported successes in performing minimally invasive surgery. This article presents a review of the current literature and a status report on current pediatric laparoscopic and thoracoscopic procedures. PMID- 7780421 TI - Psychosocial factors affecting a child's capacity to cope with surgery and recovery. AB - Medical stressors associated with illness and surgery make extraordinary psychological demands on children. A child's coping abilities, both emotional and cognitive, are at the heart of adjustment to these demands. Social support is also an important element in the child's ability to recover psychologically. Finally, a child's previous medical experiences, psychiatric problems, and learning disabilities may affect the child's behavior. PMID- 7780422 TI - Child-focused perioperative education: helping children understand and cope with surgery. AB - It is essential for all health care providers to remember that children experience hospitalization and perioperative experiences differently than adults because of their development stage and personal life experiences. Advocating for preparatory and concurrent perioperative education and support continues to be supported in the literature. Therapeutically based play and support can be adapted throughout the perioperative setting, from start to finish. It can also promote understanding, compliance, and satisfaction for both the child and family, and can provide the health care worker with a more satisfying patient focused plan of care. PMID- 7780423 TI - Preoperative assessment of the infant, child, and adolescent. AB - The preoperative nursing assessment is a valuable tool for perioperative nurses. This article describes the pediatric history, approach to pediatric physical examination, methods of examination, and a system-by-system review of important considerations for the pediatric patient. PMID- 7780424 TI - Blood pressure measurement in children: a brief review. AB - Blood pressure measurement in children is difficult and many inaccuracies are seen because of the method of measurement of the blood pressure cuff and the choice of apparatus with which to measure the blood pressure. This article will briefly review the ways in which blood pressures are measured in children and the accuracy of these different measures. Perioperative nurses should be acutely aware of the confusion in literature concerning blood pressure measurement in children. It is hoped that this discussion will help the perioperative nurse to choose the appropriate size cuff and the most accurate method of measurement. PMID- 7780425 TI - Model of human transitional cell carcinoma: tumor xenografts in upper urinary tract of nude rat. AB - An in vivo model for the study of human transitional cell carcinoma (TCC) in the urinary tract is desirable. Orthotopic xenografts are useful in order to approximate better the behavior of human tumor cells in situ. Prior models have been described in the urinary bladder of the nude mouse and rat. We have developed the first model of implantation of human TCC in the upper urinary tract of an experimental animal. The kidneys of homozygous nude rats 4 weeks of age were inoculated with 1-5 x 10(6) cells of the RT4 well-differentiated papillary human TCC line through bilateral flank incisions, with transparenchymal injection of tumor cells into either the collecting system (renal pelvis) or the parenchyma. The overall implantation rate was 92% (54/59 kidneys). However, implantation into the collecting system occurred in only 45% (18/45) of the group. Ligation of the ureter prior to inoculation to produce urine stasis improved the mucosal implantation rate. Despite suspect urine cytology findings in the renal pelvis injection group, no distal seeding of the urinary tract was seen. Intraparenchymal tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumors. Vascular and lymphatic invasion were commonly seen; however, distant metastasis was not observed. This model will prove useful in determining the role of seeding in recurrent disease and in developing less invasive modalities for the treatment of upper tract TCC. PMID- 7780426 TI - Evaluation of optimal stent size after endourologic incision of ureteral strictures. AB - The stent size necessary to promote optimal ureteral healing after an endoureterotomy is not known. We compared healing of an endoureterotomy over a 7F indwelling ureteral stent with healing over a 14F endopyelotomy stent. A midureteral stricture was created in each of 25 anesthetized female minipigs using an electrified stone basket passed retrograde. Six weeks later, the stricture was incised with a 24F cutting balloon device. Twenty pigs were randomized to receive a 7F or a 14F stent; four control pigs received neither incisions nor stents. At 1 week, a radiograph was performed to confirm proper stent position, and the stents were removed. At 3 months, a retrograde ureterogram was performed, and the ureters were examined grossly and harvested for histologic studies. Two of the ten pigs in each study group developed a recurrent stricture. The use of a 14F stent provided no advantage over the use of a smaller, more easily positioned 7F stent. PMID- 7780427 TI - Nephron-sparing laparoscopic surgery: techniques to control the renal pedicle and manage parenchymal bleeding. AB - Laparoscopic nephron-sparing surgery has been limited by several factors, including problems in the control of the vascular pedicle and the management of parenchymal bleeding. In an effort to improve the efficacy of laparoscopic nephron-sparing surgery, we developed and tested several techniques to control and manage intraoperative renal bleeding while performing 30 laparoscopic anatrophic nephrolithotomies using the porcine model. Control of the renal pedicle and management of bleeding included the use of the following: (1) extracorporeally applied atraumatic vascular pedicle clamp; (2) Argon Beam Coagulator to perform the capsulotomy; (3) electrocautery scissors to perform the nephrotomy; (4) Gelfoam welded to the cut surface of the parenchyma with the argon beam coagulator; (5) Surgicel welded to the outer surface of the kidney with the Coagulator; and (6) laparoscopically applied bolster sutures to further stabilize the renal unit. All animals tolerated the procedure well and survived to their appointed date of sacrifice. We conclude that these techniques may improve the efficacy of laparoscopic renal surgery, including nephron-sparing procedures. PMID- 7780428 TI - Alternative endoscopic management in the treatment of urethral strictures. AB - Advances in endoscopic instrumentation and techniques have expanded our armamentarium for safe and effective treatment of urethral strictures. Endoscopic incision or dilation should remain the preferred treatment for uncomplicated primary strictures. Balloon dilation can be useful in the treatment of dense strictures. Incision using laser energy has yet to provide better results than procedures employing a cold knife. As such, it would be difficult to justify the added expense of laser urethrotomy. Endoscopic placement of free skin grafts into the bed of the urethra after transurethral resection or deep incision of the stricture is a novel approach that has shown a great deal of promise. Endourethroplasty is a reasonable alternative to open urethroplasty when treating long strictures, as more than 90% of the reported patients have had a successful outcome with no recurrence. However, larger experience with this procedure is necessary to verify its efficacy and for greater acceptance. The placement of indwelling stents is another new promising treatment option. Overall short-term success rates range from 75% to 100%, but the follow-up period is short, and little is known about the long-term risks of an indwelling foreign body in the urethra. Endoscopic incision via "cut-to-the-light" or "core-through" procedures is an excellent alternative in patients with obliterative strictures. Data from several centers reveal that the majority of patients gain relief of obstruction while maintaining continence and erectile potency. However, at least 25% of these patients will need further endoscopic management to maintain urethral patency. PMID- 7780429 TI - Use of continuous-infusion alfentanil for analgesia during spark-gap lithotripsy. AB - The painful stimuli produced by a new generation of electrohydraulic/electromagnetic lithotripters are such that continuous infusion analgesia rather than general or regional anesthesia is appropriate. We describe our experience with continuous alfentanil infusion supplemented with intravenous bolus midazolam in caring for patients treated with an unmodified Medstone STS 1050 lithotripter. Ninety consecutive treatments using this technique averaged 63 minutes, compared with 69 minutes for 14 treatments done with general anesthesia and 88 minutes for 58 treatments done with epidural anesthesia. The stone burden, kilovoltage, and number of shocks were similar for the three groups, as was the immediate stone fragmentation rate. Only 2 of 90 patients received inadequate analgesia with the intravenous technique and required the induction of general anesthesia. Continuous-infusion analgesia appears sufficient to blunt the stimulus provided by the unmodified spark-gap lithotripters still in common use. PMID- 7780430 TI - Functional and histologic alterations in growing solitary rat kidney as result of extracorporeal shockwaves. AB - The long-term effects of extracorporeal shockwave lithotripsy (SWL) on children treated for renal calculi are unclear. To study the effects on the immature animal, we evaluated 31 Wistar white rats that underwent right nephrectomy at 30 days of age. At 40 days of age they were divided into three groups: a control group of 10 rats that received no shockwaves; Group I (9 rats) that received 1000 shockwaves at 16.0 kV, and Group II (12 animals) that received 1000 shock waves at 17.2 kV. Six months later at maturity (7 months and 10 days of age), the following parameters were measured: (1) body and renal weight; (2) blood lithium, sodium, potassium, and creatinine; (3) fractional lithium, sodium, and potassium excretion; and (4) clearances of lithium and creatinine. The kidneys were studied grossly and histologically. We found no significant changes in overall animal and renal growth between the post-SWL and control groups. However, there were significant changes in renal function. The animals in Groups I and II presented significant increases in blood potassium compared with the control group. Furthermore, the 1000 x 17.2 kV group showed permanent histologic renal changes, including red cells in Bowman's capsule and glomerular congestion. The disorders caused by SWL are compatible with hyporeninemic hypoaldosteronism, inappropriately low plasma renin activity, and aldosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780431 TI - Metabolic evaluation of infected renal lithiasis: clinical relevance. AB - Complete metabolic evaluation was performed in 21 patients with infected renal lithiasis. Patients with pure struvite stones (struvite +/- carbonate apatite) were significantly less likely to have metabolic abnormalities than patients who had struvite +/- carbonate apatite+calcium oxalate (2 of 14 v 7 of 7, P = 0.0003). Urine calcium excretion was markedly higher in the mixed stone group than the pure struvite group (342 +/- 98 mg/24 h v 136 +/- 82 mg/24 h; P < 0.0001). The differing opinions among researchers regarding the likelihood of finding metabolic abnormalities in patients with urolithiasis and infection probably reflect differences in the definitions of the populations studied. If patients with calculi containing only struvite +/- carbonate apatite are evaluated, we believe that few significant metabolic abnormalities will be identified. PMID- 7780432 TI - Laparoscopic unroofing of symptomatic renal cysts: three distinct surgical approaches. AB - Although they are rarely associated with complaints, benign renal cysts may be the cause of pain, hypertension, or other problems. Simple aspiration is rarely definitive treatment. We have had good results with three laparoscopic approaches to cyst unroofing: transperitoneal, with reflection of the colon medially or dissection through the mesocolon and direct retroperitoneoscopy. We recommend initial percutaneous aspiration with cytology study both to rule out malignancy and to identify those cysts clearly in need of unroofing. PMID- 7780433 TI - Laparoscopic cystectomy and ileal conduit: case report. AB - A completely new combined laparoscopic cystectomy and ileal conduit technique for removal of an infiltrating bladder cancer was carried out on a 64-year-old woman. The bladder was dissected free and extracted whole through the right flank. The right ureter and a loop of intestine were withdrawn through the same incision. An ileal segment was isolated and intestinal continuity restored. The right ureter was anastomosed to one extreme of the segment that was then reintroduced into the abdomen, taken across to the left side, withdrawn with the left ureter, anastomosed extracorporeally, and reintroduced. The stoma was constructed in the left flank at the patient's request. Recuperation was unusually fast and painless, and little postoperative analgesia was required. Further experience and a two-team approach could reduce the operation time to 3 or 4 hours. We are now convinced that combining the two procedures was better for the patient, even though it prolonged the time in the operating room. PMID- 7780434 TI - Intraperitoneal versus extraperitoneal insufflation of carbon dioxide as for laparoscopy. AB - In order to compare the effects of intraperitoneal and extraperitoneal insufflation of CO2, we obtained blood gas measurements and chest radiographs in dogs during insufflation into three sites: the peritoneal cavity alone, the retroperitoneal space with communication into the peritoneal cavity, and the retroperitoneal space alone. The blood pH fell a mean of 0.11 +/- 0.03 and the PaCO2 rose a mean of 16.0 +/- 3.7 mm Hg when insufflation included the peritoneal cavity, whereas when insufflation was limited to the retroperitoneum, the pH fell a mean of 0.05 +/- 0.03 and the PaCO2 rose a mean of 7.5 +/- 2.8 mm Hg. Extrapleural thoracic dissection of gas was noted in one animal after insufflation limited to the retroperitoneal space. These findings confirm that there is significant absorption of CO2 from the peritoneal cavity during laparoscopy with CO2 insufflation, whether the pneumoperitoneum is primary or occurs secondary to retroperitoneal insufflation. If the insufflated gas is limited to the retroperitoneal space, however, the absorption of CO2 appears to be reduced in this animal model. The risk of thoracic dissection of gas may be greater during extraperitoneal insufflation than during intraperitoneal insufflation. PMID- 7780435 TI - Retroperitoneoscopy: effects of insufflation media on surrounding tissue during balloon rupture. AB - There has been recent interest in using balloon dilation to create an extraperitoneal working space to perform retroperitoneoscopy. Balloon dilation is not without risk, and incorrect placement or rupture can result in tissue damage. We developed an ex vivo model to assess the effect of various filling media on tissue injury during balloon rupture. As would be expected from theoretical considerations, greater energy was released during rupture of the gas-filled balloon than a liquid-filled balloon. These data indicate that liquid filling medium is preferable to gas when creating an extraperitoneal working space. PMID- 7780436 TI - Outcome of extracorporeal shockwave lithotripsy monotherapy for large renal calculi: effect of stone and collecting system surface areas and cost effectiveness of treatment. AB - The treatment options for large renal calculi are controversial. We report on our experience with 65 treatments of renal calculi > 3 cm using extracorporeal shockwave lithotripsy (SWL) monotherapy. We stratified our results according to stone and collecting system surface areas (measured by computer image analyses), stone location, and stone type. The overall success rate of SWL monotherapy was 27% at 3 months. The best stone-free rate (60%) was obtained for stones < 500 mm2 and located primarily within the renal pelvis. The stone-free rate for stones with surface areas > 1000 mm2 was only 8%. None of the cystine stones was treated successfully, whereas 80% of patients with uric acid stones became stone free. We estimated an average cost of $67,048 to render a patient with a large renal calculus stone free using SWL monotherapy. We recommend that other treatment options, such as percutaneous nephrolithotomy, be considered as first-line therapy for large renal calculi. PMID- 7780437 TI - Noninvasive quantitative method for measuring isovolumetric bladder pressure and urethral resistance in the male: I. Experimental validation of the theory. AB - Noninvasive measurement of intravesical pressure, impulsive flow rate, and localized urethral resistance is achieved by clamping the penis immediately above the glans with a pneumatic cuff and then instructing the patient to initiate voiding. The cuff is then deflated slowly until urinary flow of at least 1 ml/s is detected and is then released rapidly to permit unimpeded flow. Cuff pressure, voided volume, and flow rate are recorded as functions of time. From the resulting tracings it is possible to determine the isovolumetric bladder pressure, the impulsive flow rate, and the flow pattern specific to the test. We studied 53 male patients demonstrating that data thus obtained are reproducible and that the cuff pressure at the initiation of voiding does measure the bladder pressure at this moment. We then modeled the lower urinary tract by an analog electrical circuit which facilitated the analysis of the urodynamic data. This analysis suggests that it is possible to separate the effects of bladder dysfunction from the effects of urethral resistance and to localize the resistance to the proximal or distal urethra without invasive testing. PMID- 7780438 TI - Passive urethral resistance to dilation in healthy women: an experimental simulation of urine ingression in the resting urethra. AB - The dynamic urethral pressure response to a simulated urine ingression was studied at the bladder neck, in the high pressure zone, and in the distal urethra in 10 healthy female volunteers. The pressure response was characterised by a steep pressure increase simulataneous with the urethral dilation, followed by a decay during the next seconds until a new equilibrium pressure was reached. The pressure decay could be described by a double exponential function in the form Pt = Pequ + P alpha e-t/tau alpha + P beta e-t/tau beta, where Pt represents the pressure at the time t, Pequ represents the pressure at equilibrium, P alpha and P beta express the decline in pressure, and tau alpha and tau beta are time constants. The size of the pressure response proved highly dependent on velocity and size of dilation as well as urethral site of measurement, with the maximum values in the high pressure zone. The time constants, on the other hand, were uninfluenced by these factors. The pressure response represents an integrated stress response from the surrounding tissues which may reflect the visco-elastic properties of the structures involved. The findings indicate that striated muscle fibres are of dominating significance for the pressure response, and the varying size of the response along the urethra is in accordance with the localization of the horseshoe-shaped rhabdosphincter, which quantitatively is the dominating circularly arranged structure around the female urethra. Functionally, the stress response will oppose any dilation, and increasingly with rising size or velocity of dilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780439 TI - Exercise pad testing in continent exercisers: reproducibility and correlation with voided volume, pyridium staining, and type of exercise. AB - This study was undertaken to determine normal values for a modified pad test to be used for testing outcomes of studies addressing therapy for exercise incontinence. Fourteen asymptomatic volunteers who were continent by history completed three similar exercise sessions wearing pre-weighed pads after ingesting phenazopyridine hydrochloride (Pyridium, Parke-Davis, Sandy, UT). The mean pad weight gain for all exercise sessions combined was 3.19 +/- 3.16 g (range 0.1-12.4). The mean area of pyridium staining was 2.66 +/- 3.14 mm. Mean volume voided after the exercise sessions was 193 +/- 108 cc (range 10-625). The Kendall coefficient of concordance used to test the interest reliability was 0.96 for pad weight gain, 0.76 for area of stain, and 0.60 for volume voided. All but one of the subjects had at least one spot of pyridium stain on at least one of the three pads. The increase in pad weight attributable to sweat and vaginal moisture is reproducible in a given individual performing the same exercise routine, but due to the large variation between subjects, we were unable to establish a cut-off value separating continence from incontinence. Adding pyridium did not improve the specificity of the test, despite instructing subjects to milk the urethra and blot before applying the pad. PMID- 7780440 TI - Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for Women Research Group. AB - This article describes short form versions of the Incontinence Impact Questionnaire (IIQ) and the Urogenital Distress Inventory (UDI). These instruments assess life impact and symptom distress, respectively, of urinary incontinence and related conditions for women. All subsets regression analysis was used to find item subsets that best approximated scores of the long form versions. The approach succeeded in reducing the 30-item IIQ and the 19-item UDI to 7- and 6-item short forms, respectively. The short form versions may be more useful than the long form versions in many clinical and research applications. PMID- 7780441 TI - Autonomic dysreflexia in a rat model spinal cord injury and the effect of pharmacologic agents. AB - The object of this study was to develop a spinal cord injury (SCI) rat model for autonomic dysreflexia (AD), assessing the effect of alpha-adrenergic and calcium channel blockade and to determine the relationship of detrusor-external sphincter dyssynergia (DESD) to the development of AD. A laminectomy was performed in male rats at the T4 or T10 level and a controlled 50 g cm blunt SCI was induced using an impounder. Four weeks after injury, changes in arterial blood pressure and heart rate were monitored while simultaneous cystometry (CMG) and pelvic floor electromography (EMG) were performed in vivo in sham (control) and spinal cord injured rats. The effects of terazosin (0.1 mg/kg), diltiazem (0.5 mg/kg), and oxybutynin chloride (0.1 mg/kg) on hemodynamic changes were assessed independently. Both T4 and T10 SCI rat displayed evidence of DESD (enhanced pelvic floor EMG activity at cystometric capacity) while control rats did not. Only T4 injured rats exhibited evidence of AD, with mean blood pressure elevations from 82.9 +/- 13.6 to 93.9 +/- 11.3 mm Hg (P < 0.01) and a mean heart rate decrease from 332.2 +/- 56.5 to 311.1 +/- 54.5 beats/min (P = 0.02) at cystometric capacity. The intravenous administration of terazosin or diltiazem abolished the AD response during CMG. The administration of oxybutynin exhibited the ability to increase bladder capacity and improve compliance in all 3 groups but did not blunt AD. The rat model of SCI effectively reproduced hemodynamic changes consistent with the AD complex in T4 level SCI but not T10 level SCI animals, despite incomplete lesions. Blockade with either an alpha-1 or a calcium channel antagonist effectively ablated the AD response to bladder distention. Anticholinergic agents had no effect on AD. DESD frequently accompanies autonomic dysreflexia, although the development of AD is not a prerequisite for DESD. PMID- 7780443 TI - Blood flow rate and total blood flow related to length density and total length of blood vessels in mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction. AB - Chronic partial bladder outlet obstruction was created in mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days the ring was removed, and after a median recovery period of 60 days the animals were sacrificed. At each study occasion the blood flow rate (ml per 100 g per min) was measured by washout of locally injected 133Xe in the bladder wall and the washout curves analyzed by the corrected initial slope method. Stereological estimation of length density and total length of blood vessels in the bladder were performed. The results can be summarized as follows: (1) no differences in the blood flow rate at the time of ring implantation, obstruction, or recovery, (2) no decrease in the blood flow rate in normal bladders after bladder distension, (3) a significant decrease in blood flow rate in obstructed bladders after distension, (4) a 6-fold increase in total bladder blood flow after obstruction, (5) an unchanged blood flow per length of blood vessels per min during the study, (6) no changes in length densities of blood vessels during the study, and (7) a 7-fold increase in total length of blood vessels after obstruction and reversion to control level after recovery. The unchanged blood flow per length of vessels implies that capillary proliferation matched the increased bladder mass during the study. PMID- 7780442 TI - Effects of diuresis on micturition. AB - Micturition can be characterized experimentally by monitoring both the frequency and volume of micturition. Previous studies demonstrated that the functional capacity of the rat and rabbit bladder, as determined by cystometry, is approximately equal to the maximal single micturition volume as recorded over a 24 hour period. Studies in many laboratories have demonstrated that chronic increases in diuresis induce increases in micturition frequency and capacity, and an increase in bladder mass. The current study compares the temporal relationship among these parameters in three models of diuresis: streptozotocin-induced diabetes in rats, sucrose-induced diuresis in rats, and furosemide-induced diuresis in rabbits. In both sucrose diuresis in rats and furosemide diuresis in rabbits there were immediate increases in both the frequency and volume of micturition. The magnitude of the increases in micturition frequency and micturition volume paralleled the increase in the total volume of urine excreted. Bladder mass increased progressively over the time course of the study. Streptozotocin-induced diabetes resulted in a more gradual (but parallel) increase in micturition frequency and volume, and again a more gradual increase in bladder mass. These studies demonstrate that functional bladder capacity is increased immediately upon the initiation of diuresis with sucrose or furosemide, as is the frequency of micturition. This indicates that functional bladder capacity is probably under neuronal regulation and the change in capacity is not a function of the increased bladder mass which occurs at a later time period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780444 TI - Total hip replacement. AB - OBJECTIVE: To provide physicians with a current consensus on total hip replacement. PARTICIPANTS: A non-Federal, nonadvocate, 13-member consensus panel representing the fields of orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, internal medicine, public health, geriatrics and biostatistics, and a public representative. In addition, 27 experts in orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, rheumatology, geriatrics, and epidemiology presented data to the consensus panel and a conference audience of 425. EVIDENCE: The literature was search through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS: The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. CONCLUSIONS: Total hip replacement is an option for nearly all patients with diseases of the hip that cause chronic discomfort and significant functional impairment. Most patients have an excellent prognosis for long-term improvement in symptoms and physical function. At this time, a cemented femoral component using modern cementing techniques, paired with a porous-coated acetabular component, can give excellent long-term results. Revision of a total hip replacement is indicated when mechanical failure occurs. Continued periodic follow-up is necessary to identify early evidence of impending failure so as to permit remedial action before a catastrophic event. PMID- 7780445 TI - Cloning and expression of two genes from Babesia equi merozoites and evaluation of their diagnostic potential. AB - High-titre equine immune sera were used to screen a lambda gt 11 expression library of Babesia equi cDNA fragments. Two cDNA clones which did not cross hybridize to each other were studied. Both clones hybridized specifically to DNA from B. equi but not to DNA from B. caballi, B. divergens or B. ovis. Recombinant proteins were expressed as glutathione S-transferase (GST) fusion proteins with apparent molecular weights of 40 kDa and 75 kDa. Polyclonal antibodies directed against the 40 kDa and 75 kDa recombinant proteins detected native antigens of 55 kDa and 50 kDa respectively in crude lysates of B. equi merozoites indicating that neither cDNA clone was full length (GST = 26 kDa). In Western blotting experiments the 75 kDa protein showed cross-reactivity with sera from horses infected with B. caballi and was not further investigated. The 40 kDa protein was additionally tested in an enzyme-linked immunosorbent assay (ELISA). A test was developed which had a calculated specificity of 99% and a sensitivity of 88% with sera from horses infected with the homologous strain of B. equi. The ELISA did not recognize sera from horses infected with B. equi strains from Brazil and Morocco. PMID- 7780446 TI - Significance of moisture content of dung pats for colonisation and degradation of cattle dung. AB - The moisture content of freshly voided cattle faeces is important with regard to colonisation by fauna and the rate of degradation of dung pats. This paper reports five trials designed to clarify the influence of small changes in moisture content of dung pats on dung breeding Coleoptera, Diptera, nematodes and earthworms and on degradation of the pats. Surface area, wet weight and organic substance content were used as parameters for measurement of degradation. Special attention was given to a trial which compared naturally voided pats with pats formed artificially from faeces of the same animals. Results indicate that small differences in moisture content of 1-2%, which may not be distinguishable by visual inspection, may have an impact on the development of Diptera, Coleoptera and earthworms and on dung degradation. PMID- 7780447 TI - Acanthocheilonema viteae: rational design of the life cycle to increase production of parasite material using less experimental animals. AB - The maintenance of the life cycle of Acanthocheilonema viteae is described with the aim to increase the production of parasite material using less experimental animals. The filaria was maintained in jirds (Meriones unguiculatus) and in soft ticks (Ornithodoros moubata). The optimal infection dosis for jirds was 80 infective larvae (L3). The mean worm number in groups of animals varied between 18 and 30 adult worms. A stable microfilaremia developed and only few animals developed pathological alterations as a consequence of the infection. A simple membrane feeding apparatus allowed mass feeding of ticks. Infection of ticks with microfilariae (mf) using this technique resulted in a mean no. of 594 +/- 527.2 L3/tick. L3 and mf were cryopreserved in liquid N2 with a simple technique. The described maintenance of the life cycle reduced the amount of required experimental animals to 30-40% of the originally needed numbers. PMID- 7780449 TI - The in vitro culture of Onchocerca spp.: I. Preliminary observations on the development of the second to the third stage larvae. AB - Second stage larvae of Onchocerca lienalis and O. gutturosa were induced to moult successfully to the third stage in vitro. Following development in their vectors Simulium ornatum s.l. and Culicoides nubeculosus the second stage larvae were kept in a cell free culture system. At least 25% of the second stage larvae of either Onchocerca species completed the moult successfully although no feeder layers had been used. In the absence of CO2 (5% in air) the number of the second stage larvae moulting successfully to the infective stage dropped to 6 and 9% respectively. PMID- 7780448 TI - Urinary schistosomiasis among school children in an endemic community in south eastern Nigeria. AB - Studies were carried out on urinary schistosomiasis among school children aged 6 to 21 in Abia State, Nigeria. Of the total 1,165 children examined for eggs of S. haematobium in their urine, 245 (21.03%) were infected. Male children had significantly (P < 0.05) higher infection (64.08%) than their female counterparts (35.92%). Age-related infection rate showed significant difference (P < 0.05) with the highest infection rate (46.94%) recorded among children between the ages of 12 and 14 years. As with infection rate, the intensity of infection was significantly higher (P < 0.05) in males (35.50 eggs/10 ml urine) then in females (28.73 eggs/10 ml urine). 4 (1.63%) of the infected individuals had heavy infection (400 eggs/10 ml urine). There was a gradual increase of mean egg count with age up to 12-14 years after which there was a decrease. Viability test showed that of the 245 children infected 151 (61.63%) had viable eggs in their urine sample. The number of males with viable eggs (62.25%) was significantly higher (P < 0.05) than the females (37.74%). Also in the number of infected individuals with viable eggs a significant difference among age groups was observed. It was significantly higher (P < 0.05) among the age group 12-14 years than in any other group. Among the infected children 38 (15.51%) had haematuria (which represents 95% of the 41 individuals with trace of blood in their urine). There was a significant association (P < 0.05) between haematuria and infection rate/intensity. PMID- 7780450 TI - Effect of temperature and humidity on egg hatch, moulting and longevity of larvae and nymphs of Dermacentor reticulatus (Ixodidae). AB - Larvae of Dermacentor reticulatus hatched at a temperature range of 20-34 degrees C, but a high egg hatch success of > 90% was only achieved at 20 degrees C and 27 degrees C and 100% r.h. The developmental capability of the eggs at low or freezing temperatures persisted up to 3 weeks at -10 degrees C and up to 8 weeks at 5 degrees C. The 50% mortality period of unfed larvae and nymphs increased with rising humidity and was longest at 5 degrees C and 100% r.h., amounting to 83.5 days for larvae and 108 days for nymphs. Engorged larvae and nymphs only moulted in the temperature range of 10-27 degrees C. The percent moulting success was low at 10 degrees C and increased with rising ambient humidity at 20 degrees C and 27 degrees C reaching more than 90% at 100% r.h. After incubation at low or freezing temperatures and subsequent transfer to 20 degrees C and 100% r.h. engorged larvae did not moult after exposure to -10 degrees C, but they tolerated 0 degrees C and 5 degrees C up to 3 and 10 weeks, respectively, and developed into nymphs. Engorged nymphs moulted into adults even after preceding incubation at -10 degrees C, their metamorphosis capability persisted for a maximum of 4 and 17 weeks at 0 degrees C and 5 degrees C, respectively. PMID- 7780451 TI - [Evidence of Cryptosporidium in children with symptomatic enteritis from the Leipzig administrative area 1987-1992]. AB - From 1987 to 1992 stool samples of 3235 diarrheic children at the age from 1 to 14 years in the Leipzig district were examined for Cryptosporidium spp. In 58 patients (= 1.8%) oocysts have been detected. Most of the positive children (= 81%) were less than 7 years old. A seasonal increasing of prevalence was observed in August and in the following months. According to anamnestic informations of treating physicians all patients were immunocompetent. The clinical symptomatology comprised diarrhoea, vomiting, fever and stomach ache. Animal contacts were known in 52% of the patients. Stool examinations for diagnosis of Cryptosporidium are recommended in unclear diarrhoeas, also in immunocompetent patients. The role of Cryptosporidium spp. as opportunists in immunodeficiency is especially commented. PMID- 7780452 TI - Managed care ... new study of 1,200 U.S. hospitals. PMID- 7780453 TI - On-line claims info comes to Los Angeles. PMID- 7780454 TI - Hospital group calls proposed Medicare cuts "devastating". PMID- 7780455 TI - The measure of Medicare services. AB - Trying to make managed care more responsive to the demands of employers and consumers is a challenge. More and more HMOs are providing financial incentives for doctors to deliver better quality and service. But critics contend that bonuses can weaken quality. PMID- 7780456 TI - Cutting off care. California's drastic reaction to illegal immigrants doesn't play well in other states. PMID- 7780457 TI - Fifth annual contract management survey. Value-driven. PMID- 7780458 TI - No breathing room in the anesthesia turf battle. AB - Anesthesiologists and nurse anesthetists have always jostled each other for work, but managed care and policy changes have brought tensions to a boil. Is the anesthesia battle a harbinger of the future? PMID- 7780459 TI - Research Triangle, NC. New competition hits the old 'Tobacco Road'. PMID- 7780460 TI - Profiles in service (1986-1995). 1992 Foster G. McGaw Prize winner. Mount Sinai Hospital Medical Center, Chicago, Illinois. PMID- 7780461 TI - Construction. Resurrection's renewal. PMID- 7780462 TI - Tax-exemption. Ready for a rumble. PMID- 7780463 TI - No smoking. Ways to clear the haze. PMID- 7780464 TI - Art therapy. Treads on threads. PMID- 7780465 TI - Teamwork. Quality converts. PMID- 7780466 TI - Homefront. When stress is relative. PMID- 7780467 TI - The faces of Medicaid. PMID- 7780468 TI - Recognizing change. PMID- 7780469 TI - Guardians and gatekeepers. PMID- 7780470 TI - Hepatitis C: past, present, and future. AB - Hepatitis C, the leading cause of chronic hepatitis in the United States, is difficult to diagnose and treat. It is vital that medical-surgical nurses understand the historical background and current information regarding prevention of hepatitis C, serological diagnosis, epidemiology and transmission, sequelae, and treatment. Issues of safety in the workplace and risks of transfusion must also be clearly understood to protect health care workers and patients receiving transfusions from infection. PMID- 7780472 TI - Current nursing practices in fever management. AB - Data regarding fever management were obtained through a retrospective or concurrent review of the medical records of 150 patients. For 41% of the patients studied, nurses notified physicians of the fever episode. The decision to treat fever was significantly influenced by fever intensity and the drawing of blood cultures, but not by age, length of hospital stay, or the duration of the fever episode. Despite recent evidence of the protective value of fever, the majority of fever episodes were treated. Acetaminophen alone, and acetaminophen in combination with physical cooling methods, were effective in lowering fever. PMID- 7780471 TI - Rationing trauma care to the elderly: an ethical dilemma. AB - It is estimated that by 2025, 25% to 35% of the people in this country will be older than 65 years. One of the hazards facing the elderly is the risk of trauma. Currently, one third of the total resources spent on trauma care are expended on the elderly, and this number will increase as the elderly segment of the U.S. population continues to grow. Despite aggressive care, the elderly trauma patient's chances of a good outcome are slim. However, is it ethical to ration trauma care on the basis of age? A case study of an elderly trauma patient provides an opportunity to apply an ethical decision-making model to the question. PMID- 7780473 TI - Research utilization: the development of a preoperative teaching protocol. AB - A research-based preoperative teaching protocol was designed for use with surgical patients at a rural midwestern hospital. A strong research base supported the development of a protocol which included an individual teaching plan adapted to the patient's fear/anxiety level. A practice-level model was designed to guide the staff nurse through the preoperative teaching process. Expected outcomes were established and an evaluation tool developed. This research utilization project improved patient outcomes and benefitted nurses and the organization. PMID- 7780474 TI - Intravenous methylprednisolone for exacerbations in multiple sclerosis. AB - Multiple sclerosis remains one of the most difficult neurological diseases to treat. It is important for medical-surgical nurses to understand the pathophysiology of multiple sclerosis, as well as recent evidence suggesting that intravenous methylprednisolone treatment may be effective for treating exacerbations of the disease. Indications and criteria for treatment, side effects, and patient teaching issues are discussed. PMID- 7780476 TI - Promoting health. PMID- 7780477 TI - Pressure ulcers: assessment to evaluation. PMID- 7780475 TI - Patient and nurse criteria for heart transplant candidacy. AB - The criteria nurses and patients believe should be used to allocate hearts for transplantation were explored and compared in a descriptive study. Although the majority of both groups agreed that patients with AIDS or who are HIV positive should not receive a transplant, the two groups agreed very little on the other criteria. This research has implications for clinical care and ethical decision making. PMID- 7780478 TI - The eggs and us. PMID- 7780479 TI - Depression and stroke patients: the keys to successful adaptation. PMID- 7780480 TI - The Internet: legal rights and responsibilities. PMID- 7780481 TI - Metformin [Glucophage]: new treatment for NIDDM. PMID- 7780482 TI - Interleukin-15 and the growth of tumor derived activated T-cells. AB - Interleukin-15 was tested to determine whether this recently discovered cytokine was capable of stimulating the growth of tumor derived activated T cells in culture (TDAC, also referred to as tumor infiltrating lymphocytes). When established cultures of IL-2 induced, IL-2 dependent TDAC were tested, IL-15 stimulated growth in a dose dependent manner, alone or in the presence of IL-2. One established TDAC was cultured with IL-15 alone for 18 passages over a 10 week period. Comparing IL-2 and IL-15 treated cultures, growth rate with IL-15 was slower. IL-15 doubled the secreted interferon alpha and granulocyte-macrophage colony stimulating factor. IL-15 and IL-2 were compared in primary TDAC cultures. IL-15 induced TDAC outgrowth in 3 of 6 cultures. IL-2 induced outgrowth in all 6. Tumor cells were eliminated as TDAC grew out in both IL-2 and IL-15 treated cultures. These results suggested that IL-15 like IL-2, is capable of stimulating the growth of TDAC with antitumor activity, but with certain distinct effects which may be of interest therapeutically. PMID- 7780483 TI - Interferon-alpha/5-fluorouracil: a novel outpatient chemo/immunotherapy for progressive metastatic renal cell carcinoma. AB - In metastatic renal cell carcinoma, most conventional antineoplastic drugs have yielded no or little efficacy. To evaluate the tolerance and therapeutic efficacy of second line chemo/immunotherapies, we treated patients with advanced metastatic renal cell carcinoma upon progression after previous antineoplastic therapy employing an outpatient combination of subcutaneous (SC) recombinant interferon-alpha (rIFN-alpha) and intravenous (IV) 5-fluorouracil(5-FU). Thirty three patients with metastatic renal cell carcinoma received SC doses thrice weekly of rIFN-alpha at 10 million U/m2 over 8 consecutive weeks. Additionally, patients received IV 5-FU at 750 mg/m2 in weeks 1-3 and 5-7; treatment cycles were repeated until disease progression. Of 33 patients, one achieved a complete remission (response duration, 24 months) and two patients presented with partial remissions (median response duration, 7 months) of pulmonary metastases upon rIFN alpha/5-FU after failing SC recombinant interleukin-2 (rIL-2) and rIFN-alpha. The present chemo/immunotherapy regimen was overall well tolerated with low to moderate systemic toxicity and predominantly constitutional symptoms i.e., fever, chills, and malaise. In summary, the second line outpatient chemo/immunotherapy regimen of SC rIFN-alpha/IV 5-FU demonstrated a limited albeit significant efficacy in pretreated patients with progressive metastatic renal cell cancer. PMID- 7780484 TI - The integration of high-dose chemotherapy and biotherapy: initial 5-year experience with autologous bone marrow transplantation in a comprehensive community cancer center. AB - Perhaps the best example of the integration of chemotherapy and biotherapy is autologous stem cell rescue following high dose chemotherapy. This analysis was undertaken to determine the outcome for patients treated in an autologous bone marrow transplant program, which was initiated in January 1989, and to illustrate the impact which biological response modifiers have had on the toxicity, survival, and costs associated with this aggressive treatment approach. Patients with metastatic cancer and good performance status were treated according to disease-specific treatment protocols. Peripheral blood stem cells [PBSC] came into use in 1990, hematopoietic colony stimulating factors [CSFs] in 1991. Outcome was monitored prospectively from the inception of the program. Five years after the program's inception, 75 patients had undergone 96 intensive chemotherapy treatments followed by autologous PBSC rescue. This included 35 patients with breast cancer, 15 with lymphoma or Hodgkin's Disease, five ovary, four melanoma, three sarcoma, three lung cancer, three leukemia, three testicular, two myeloma, one non-lung small cell carcinoma, and one medulloblastoma. Twenty-one patients underwent back-to-back cycles of intensive therapy and rescue; 14 of whom had breast cancer. Twelve patients were treated in 1989, 14 in 1990, 18 in 1991, 14 in 1992, and 17 in 1993. While four of the first 12 patients died within 60 days of reinfusion of cells in 1989, no patients have died within this time frame as a direct result of therapy during the subsequent four years. No patients have been lost to follow-up. Median survival was only eight months in 1989, but has not been reached for subsequent years. For all patients, median failure-free survival (FFS) is 17.2 months; 1-year FFS is 57%, 2 year 36%, and 3-year 29%. Median overall survival (OS) is 30.4 months; 1-year OS 66%, 2-year 52%, and 3-year 42%. From 1990-1993, for patients with metastatic breast cancer (21), and recurrent lymphoma (15), FFS and OS are comparable to the best results published from academic teaching hospitals. Twenty-one patients have survived over two years, 18 of whom continue in remission. Patients were hospitalized for an average of 31 days in 1989, 28.9 in 1990, 24.5 in 1991, and only 13.0-14.0 days in 1992-1993. Two patients were treated entirely as outpatients. Average hospital charges for the 96 treatments have been $120,000 with a range of $15,000 to $461,000, and currently average around $100,000.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780485 TI - Augmentation of specific tumor killing activity by tumor-infiltrating lymphocytes (TIL) in the presence of TNF-SAM2. AB - The effect of TNF-SAM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h 51Cr-release assays in the presence or the absence of TNF SAM2. In the presence of TNF-SAM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-SAM2. Direct cytotoxicity by exogenously added TNF-SAM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-SAM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-SAM2 and the cytotoxicity shown by TNF-SAM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer. PMID- 7780486 TI - Diabetes mellitus in cancer patients treated with combination interleukin 2 and alpha-interferon. AB - Diabetes mellitus is thought to be an autoimmune disease caused by destruction of beta cells in pancreatic islets. Insulin resistance in the peripheral tissues may also play a role. Both interleukin 2 (IL-2) and alpha interferon can enhance immune function by stimulating formation of cytolytic T cells and/or antigen expression on both normal and tumor cells. This report describes three patients with advanced malignancy who were treated with combination IL-2 and alpha interferon who had the onset or worsening of diabetes mellitus. One patient died as a result. There is evidence that interferon can increase insulin resistance and it is likely that both agents can initiate or enhance an ongoing autoimmune process. Physicians using this combination of drugs should be aware of this potential serious toxicity. PMID- 7780487 TI - Subcutaneous interleukin-2 and alpha-interferon in advanced colorectal carcinoma. A phase II study. AB - Subcutaneous administration of low doses of recombinant interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) on an out-patient basis has been reported not to significantly compromise the response frequency compared to intravenous IL-2 in patients with renal cell carcinoma and melanoma. As part of an ongoing program to develop a biotherapeutic concept in patients with colorectal carcinoma (CRC) we studied the clinical effects of such a regimen in 15 patients with metastatic CRC. The daily dose of IL-2 varied between 4.8-14.4 x 10(6) U/m2 and of IFN-alpha between 3-6 x 10(6) U/m2. The cycle length was 6 weeks. The course was repeated every 8 weeks until disease progression. Maximum 4 cycles were administered. Maintenance therapy was given to responding patients once a week every month. No patient showed a major response (CR or PR). Six patients had a stable disease ranging from 3 months to 18 months with a median duration time of 5 months. The median survival of all patients was 13 months. The main adverse reactions were fever, chills, anorexia and shortness of breath. No treatment related deaths occurred. 6/14 patients developed abnormal concentration of serum levels of thyroid hormones. It is concluded that the present treatment schedule using IL-2 and IFN-alpha in advanced CRC seemed not to be of clinical benefit. PMID- 7780488 TI - Correlation between malignancy level of AKR lymphoma variants and sensitivity to hyperthermia. AB - The tumor progression process has been found to be accompanied by various cell membrane modifications. This cell organelle may therefore be considered as a target for drugs directed against tumor cells of advanced cancer. Hyperthermia acts on tumor cells largely, although not only, via an effect on the cell membrane. In the present study, the in vitro effect of hyperthermia on the tumorigenicity of cells derived from two AKR lymphoma variants of malignancy, TAU 39 of low (LM) and TAU-38 of high-malignancy (HM), was compared. The cells of the HM variant were markedly more sensitive to hyperthermic treatment than those of the LM one. Pretreatment of cells at 41 degrees C or 43 degrees C resulted in a more marked delay in tumor appearance in mice injected with the HM than in those inoculated with the LM variant. Moreover, in mice inoculated with cells pretreated at 45 degrees C, long term survivors were found only in those inoculated with the HM variant. These results corroborate our previous data regarding the effect of hyperthermia on metastatic and primary tumor cells of AKR lymphoma as well as the F1 and F10 variants of B16 melanoma. PMID- 7780489 TI - Can the Year 2000 objective for reducing overweight in the United States be reached?: a simulation study of the required changes in body weight. AB - AIM: The purpose of this analysis was to estimate the magnitude of weight change required in the six-year period between 1994 and the Year 2000 if Americans are to reach the Healthy People 2000 goal for reduction of overweight among those ages 20-74 to no more than 20% among all adults and no more than 30% among black women. Prevention of weight gain among the non-overweight is compared with that of weight loss among the overweight as strategies for reaching this goal. DESIGN: Data from the First National Health and Nutrition Examination Survey (NHANES I) and the Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) were used to estimate 6-year weight change of persons aged 20 to 72 at the Year 2000. Men, white women, and black women were examined in addition to the overall population. Given a baseline prevalence of 24.7%, overweight in the year 2000 was projected for three simulated interventions: no weight gain among non-overweight persons (prevention-only), weight loss among overweight persons (weight-loss only), and prevention-plus-weight-loss. In addition, the Year 2000 overweight prevalence was projected under different baseline prevalence scenarios of 26% and 34%. OUTCOME MEASURE: Prevalence of overweight; overweight determined by body mass index (> or = 27.3 kg/m2 for women and > or = 27.8 kg/m2 for men). RESULTS: Prevention-only was successful in reducing the overall prevalence of overweight from 24.7% to 20%. Weight-loss-only required a 5.3 kg weight loss to achieve the overall goal of 20% and 8.4 kg weight loss to achieve the goal within all three race-sex strata. Prevention-plus-weight-loss required only 3.8 kg of weight loss to achieve the goals within the three race-sex strata. Prevention-only was not successful in reducing the overall prevalence of overweight to 20% when the 26% and 34% baseline scenarios were used. Weight-loss-only required 6.3 and 11.2 kg; prevention-plus-weight-loss required 1.2 and 6.6 kg of weight loss using the 26% and 34% baselines, respectively. CONCLUSIONS: Prevention of weight gain among those who are not already overweight could achieve substantial changes in the prevalence of overweight, even in a 6-year time period. However, given the increasing trend in overweight, the Year 2000 goal for the reduction in prevalence of overweight will not be reached. PMID- 7780490 TI - Modernity and obesity in coastal and Highland Papua New Guinea. AB - OBJECTIVE: To investigate the association between individual degree of modernization and obesity in Papua New Guineans using a score of relative 'modernity'. DESIGN: Cross-sectional survey in six populations with varying degrees of modernity. Independent effects of modernity score, components of modernity score, age and physical activity were assessed in relation to general obesity (body mass index (BMI)) and body fat distribution (waist-hip ratio (WHR)). A sub-study of the relationship between diet and modernity was also performed. SETTING: Population-based samples of subjects in three Highland and three coastal locations in the developing country of Papua New Guinea (PNG). SUBJECTS: 1877 subjects > or = 25 years of age attended the survey. MEASUREMENTS: Age, physical activity, BMI, WHR, 2-h oral glucose tolerance test, and modernity score, based on area of origin, father's employment, type and duration of individual's employment, education, years in an urban centre, housing type and spouse score. RESULTS: More modern subjects had higher mean BMI and lower levels of physical activity, and mean WHR also varied with modernity in men but not women. In linear regression analysis, total modernity score was significantly associated with both BMI and WHR in men and women, independently of age and physical activity. When components of the modernity score were examined, younger age, more sophisticated housing and increasing number of years in an urban centre were independently associated with BMI in men and women, while education level and reduced physical activity were also significant predictors in men. Associations with WHR were weaker. Results of the dietary sub-study suggested that the lowest energy and nutrient intakes occurred in the least modern men and women. CONCLUSION: Aspects of modernity, such as more sophisticated housing and greater number of years spent in an urban centre, may be markers of higher income and increasing adoption of Western ways, which in turn are associated with physical inactivity and increased availability of energy-dense Western food, thus promoting obesity in this rapidly developing Pacific nation. PMID- 7780491 TI - Effect of dexfenfluramine on energy expenditure in obese patients on a very-low calorie-diet. AB - AIM: To investigate the effect of dexfenfluramine (dF) on Energy Expenditure (EE). DESIGN: 20 obese females were studied in a double-blind design. Pre-diet and at 14 and 28 days of VLCD and dF treatment (30 mg/d) or placebo, Resting Metabolic Rate (RMR), 3 h-Thermic Effect of Food (3 h-TEF) and body composition were determined. EE and body composition were measured by indirect calorimetry and bioelectrical impedance, respectively. RESULTS: No differences between groups were observed in relation to weight loss, body composition changes or RMR. At 3 h postprandial, the EE was still elevated in both groups. No changes on TEF were observed in the placebo group during VLCD. In contrast, TEF decreased in dF group during VLCD (P < 0.05). No significant differences in TEF at the end of the study were observed between groups. CONCLUSION: These results suggest that dF modifies 3 h-TEF but not RMR in obese patients during VLCD administration. PMID- 7780492 TI - Associations between different anthropometric measurements of fatness and metabolic risk parameters in non-obese, healthy, middle-aged men. AB - OBJECTIVE: To investigate whether body fatness influences the metabolic risk profile in a group of healthy, normal-weighted men and to determine which anthropometric measurements that are most closely associated with the risk profile in this group of men. DESIGN: A cross-sectional study where total fatness and abdominal fatness were determined by older (BMI, WHR, impedance) and more recent anthropometric indices (sagittal diameter (SD) and conicity index (Valdez et al., Int. J. Obes. 1993; 17: 955)). The metabolic risk profile was determined by lipoproteins, insulin, glucose and blood pressure. SUBJECTS: The study comprised a homogeneous group of 58 men who were all healthy and normal-weighted (BMI = 24.2 +/- 1.8) and were all 44 years old. RESULTS: In relation to total fatness, BMI was more closely correlated to the various risk parameters than the fat mass determined by bioelectrical impedance independent of using several different equations in estimating the fat mass. From simple comparison of correlation coefficients, SD and SDH (SD/height) seemed to be the best indices of abdominal fatness in predicting an enhanced metabolic risk profile. The conicity index was considerably inferior in comparison to the other indices of abdominal fatness. In multiple regression analysis abdominal fatness as determined by SD or SDH explained most of the variation in the metabolic risk profile and no significant influence of total fatness (BMI) was found when taking the influence of abdominal fatness into account. The most pronounced effect of abdominal fatness in these non-obese men was a reduction of HDL-cholesterol, an elevation of the triglycerid level and an elevation of the insulin level. CONCLUSION: Thus, even a minor accumulation of adipose tissue in the abdominal region in these otherwise non-obese men was associated with a considerably adverse metabolic risk profile. SD or SDH seemed to be slightly more correlated to the risk profile than other anthropometric indices of abdominal adipose tissue mass (e.g. WHR). The new conicity index was inappropriate for predicting the risk profile associated with abdominal fatness in these non-obese men. PMID- 7780494 TI - Dexfenfluramine treatment of obesity: a double blind trial with post trial follow up. AB - OBJECTIVE: As successful weight management demands a long term approach, a better understanding of weight changes during and for significant periods after cessation of dexfenfluramine therapy is essential to the evaluation of the drug's effectiveness in clinical practice. This study aimed to investigate additional benefits to weight loss during 6 months treatment with dexfenfluramine in 60 patients enrolled in a weight loss programme. DESIGN: Sixty obese subjects (21 males; 39 females) were randomised to dexfenfluramine (15 mg twice daily) or placebo for six months. Fifty one (27 dexfenfluramine; 24 placebo) subjects completed the double blind, randomised, placebo controlled clinical trial. RESULTS: After a one month 'run in' phase and six months treatment, weight loss in the dexfenfluramine group was significantly greater than placebo, 9.7 +/- 1.1 kg vs 4.9 +/- 0.9 kg (mean +/- s.e.m.); P = 0.002. Reduction in body fat, 5.0 +/- 0.7 kg vs 1.0 +/- 0.9 kg; P = 0.002 and waist circumference, 10.5 +/- 1.9 cm vs 5.7 +/- 1.1 cm; P = 0.04 was also greater in the dexfenfluramine group. Despite significant weight loss, waist to hip ratio (WHR) did not change in either group. The dexfenfluramine group reported a significantly greater incidence of nausea, dry mouth and dizziness which tended to decrease as treatment progressed. No subjects withdrew due to drug induced side effects. Reduction in serum triglyceride levels and an increase in HDL cholesterol (in female subjects) in conjunction with a reduction in fasting insulin, collectively support an improved cardiovascular risk profile in the dexfenfluramine group. Despite significant weight loss, these risk factor measurements worsened in the placebo group. After cessation of dexfenfluramine therapy, there was a significantly greater weight regain indicating a loss of treatment effect. By 5 months after cessation of dexfenfluramine, the treatment effect was negated with weight loss in the dexfenfluramine (6.0 +/- 1.6 kg) and placebo (6.2 +/- 1.3 kg) group, similar. CONCLUSION: The results of this study support the longer term use of dexfenfluramine therapy for patients with chronic obesity. PMID- 7780493 TI - High fasting insulin levels associated with lower rates of weight gain in persons with normal glucose tolerance: the San Luis Valley Diabetes Study. AB - OBJECTIVE: to investigate whether increased insulin resistance is associated with a reduced risk of weight gain among Hispanic and non-Hispanic white persons in Colorado. DESIGN: measurements were taken at baseline and after an average of 4.3 years. SUBJECTS: 789 normal glucose tolerant subjects 20 to 74 years of age were studied. MEASUREMENTS: fasting insulin levels were used as an indirect marker of insulin resistance. RESULTS: the average baseline body mass index (BMI) was 26.1 (+/- 3.6 s.d.) in men and 25.2 (+/- 4.4 s.d.) in women. The average weight change at follow-up was 0.8 kg (+/- 4.3 s.d.) in men and 1.3 kg (+/- 5.0) in women. A doubling in initial fasting insulin was associated with a reduced risk of gaining 5 kg (n = 134) and 10 kg (n = 24) of weight in logistic regression models (OR5kg = 0.76, 95% CI: 0.59, 0.99 and OR10kg = 0.61, 95% CI: 0.36, 1.02). Similarly, a doubling of initial fasting insulin was associated (P = 0.006) on average with a 6.3 kg less weight gain in linear regression models, independently of initial body weight, age, sex, ethnicity and BMI. The relation was consistently observed in men and women and in both ethnic groups. CONCLUSION: higher initial fasting insulin decreases the risk of subsequent weight gain in both Hispanic and non Hispanic white normal glucose tolerant individuals similar to Pima Indians. This appears to be a common biologic characteristic in moderate to low as well as high risk populations for NIDDM. PMID- 7780495 TI - Child's home environment in relation to the mother's adiposity. AB - OBJECTIVE: There are conflicting findings regarding the role of non-genetic family factors on obesity in children, but specific characteristics of the family environment that may influence childhood obesity have not been identified. The purpose of the present study was to explore the association between mother's adiposity and family environment factors that could influence the child's risk of obesity, primarily through effects on eating and physical activity behaviors. DESIGN AND MEASURES: Cross-sectional, correlational study. Adiposity was estimated by the sum of mothers' triceps and subscapular skinfolds. Family environment measures were assessed by direct observation and by structured interviews with mothers. SUBJECTS: A sample of 347 mothers of preschool children were assessed. RESULTS: Mother's adiposity was related to marital status, with married mothers having thicker skinfolds. Only two of 23 family environment variables were significantly correlated with mother's adiposity, and both of these variables were related to television. The demographic and family environment variables accounted for only 4% of the variance in mothers' skinfolds. CONCLUSION: The present study identified few characteristics of the family environment that were related to mother's adiposity. PMID- 7780496 TI - No evidence for a chronic effect of smoking on energy expenditure. AB - OBJECTIVE: To investigate whether effects of smoking on energy expenditure (EE) extend chronically beyond smoking the last cigarette. DESIGN: Eight subjects (5M,3F) were studied over three consecutive months, after smoking as normal (S) on 1-3 occasions, and after not smoking for 4-8 weeks (NS) on 1-2 occasions. On each occasion subjects underwent one 32-h measurement of EE in a respiration chamber (8-h overnight plus a 24-h day, with no smoking in the chamber) and one measure of basal metabolic rate (BMR) on exit from the chamber. Statistical differences were determined using paired t-tests. RESULTS: There were no differences between S and NS for any of the EE measures, either including (n = 8) or excluding (n = 5) three subjects whose urinary cotinine excretions suggested failure to stop smoking during NS. For S and NS (N = 5) respectively, overnight EEs during the first night in the respiration chamber were 2.08 +/- 0.38 and 2.10 +/- 0.42 MJ/8-h; 24-h EEs during 12-36 hours after the last cigarette were 8.38 +/- 1.6 and 8.24 +/- 1.34 MJ/day, and BMRs were 6.51 +/- 1.21 and 6.50 +/- 1.07 MJ/day. CONCLUSION: We found no evidence for a chronic effect of smoking on EE. PMID- 7780497 TI - Breast size as a determinant of breast cancer. AB - OBJECTIVE: To determine whether breast size as reflected in cup size is independently associated with Wolfe's mammographic patterns. DESIGN: Univariate and multivariate associations between the waist/hip ratio (WHR), body mass index (BMI), cup size, age, parity, age at menarche menopausal status and Wolfe's mammographic parenchymal patterns were determined by (multiple) linear logistic regression. SETTING: Population based mammographic breast cancer screening project. SUBJECTS: 7819 women between 39 to 52 years of age. RESULTS: The univariate analysis demonstrated that women in the lowest tertile with respect to BMI and WHR when compared to women in the upper tertile were significantly more likely to display the high risk P2, Dy breast patterns. Cup size showed a similar inverse relation with the P2, Dy patterns. When age, WHR and BMI are entered together in the multivariate model the relation between cup size and the P2 Dy patterns is no longer significant in the upper tertile. CONCLUSION: Breast size is not a major independent determinant of the high risk P2, Dy parenchymal breast patterns when the WHR and BMI are taken into account. PMID- 7780498 TI - The effect of standardising the body mass index for relative sitting height. AB - The body mass index (BMI) has become a universal index of energy nutritional status in adults even though it is influenced by many factors other than energy stores. One of these is variation in height caused by variation in the length of the trunk and legs. Such variations occur between and within populations. In the British population, with a sitting height/stature (SH@S) ratio at the mode of population values, adjustment of BMI for SH/S ratio caused BMI to change by 1 kg/m2 or more in 33% of women and 10% of men and by 2 kg/m2 in 5% of women and 1% of men. The possible effects of shape, as evinced by SH/S ratios should be borne in mind when describing individuals or populations as overweight or obese in epidemiological studies and in decisions of clinical management. PMID- 7780499 TI - Professor Vladimir Dilman. PMID- 7780500 TI - In vitro reconstitution of progesterone-dependent RNA transcription in nuclear extracts of human breast carcinoma cells. PMID- 7780501 TI - Plastid in vitro transcription. PMID- 7780502 TI - Microinjection of in vitro transcribed RNA and antisense oligonucleotides in mouse oocytes and early embryos to study the gain- and loss-of-function of genes. PMID- 7780503 TI - mRNA translation in Xenopus oocytes. PMID- 7780504 TI - Transcription system using a HeLa cell mitochondrial lysate. PMID- 7780505 TI - The Xenopus egg extract translation system. PMID- 7780506 TI - In vitro translation using rabbit reticulocyte lysate. PMID- 7780507 TI - Translation using a wheat-germ extract. PMID- 7780508 TI - In vitro transcription and translation in a cell-free system from Clostridium tetani. PMID- 7780509 TI - Preparation and use of E. coli S-30 extracts. PMID- 7780510 TI - Posttranslational transport and in Thylakoido integration of plastid protein. PMID- 7780511 TI - Import into isolated yeast mitochondria of radiolabeled proteins synthesized in vitro. PMID- 7780512 TI - Quantitative measurement of mRNA using the RNase protection assay. PMID- 7780513 TI - Structure-function studies based on in vitro expression. PMID- 7780514 TI - Sigma-like plastid transcription factors. PMID- 7780515 TI - Preparation of HeLa nuclear extracts. PMID- 7780516 TI - Purification of the human TATA-binding protein, TBP. PMID- 7780517 TI - DNA-binding studies using in vitro synthesized Myb proteins. PMID- 7780519 TI - Gene isolation by screening lambda gt11 expression libraries with DNA-binding site probes. PMID- 7780518 TI - DNase I footprinting using PCR-generated end-labeled DNA probes. PMID- 7780520 TI - Transcriptional activation analysis by the chloramphenicol acetyl transferase (CAT) enzyme assay. PMID- 7780522 TI - Antisense affinity depletion of RNP particles. Application to spliceosomal snRNPs. PMID- 7780521 TI - Assembly and transcription of chromatin templates using RNA polymerase III. PMID- 7780523 TI - In vitro mRNA editing using S100 extracts. PMID- 7780524 TI - The role of quantitative modelling in health care. PMID- 7780525 TI - Should you eat breakfast? Estimates from health production functions. AB - This paper uses an econometric specification based on the health production function approach to examine the importance of lifestyles for adult health. The approach treats health practices such as eating breakfast, smoking, and exercise as inputs into the production of good health; several output measures are explored. The econometric models estimated with data from the 1985 Health Interview Survey show broad agreement with conventional wisdom about the importance of healthy lifestyles. This paper also investigates the role schooling plays in the production of good health. Schooling is found to be related to good health even after controlling for differences in observable health inputs. However, lack of support for a plausible specification of the productive efficiency hypothesis casts some doubt on the interpretation that schooling increases the efficiency of the household production of health. PMID- 7780527 TI - An economic model of the market for hospital treatment for non-urgent conditions. AB - This paper develops an economic model of the market for treatment of waiting list conditions, in which complainants choose between private treatment, NHS treatment and no hospital treatment. This choice depends on a number of clinical and non clinical factors, which enter the demand functions for private and NHS treatment. Among the key influences are the price of private treatment and the expected duration of wait for NHS treatment, both of which are endogenous variables in the model. Given a pair of private sector and NHS supply functions, expressions are obtained for the price and expected wait at which demand and supply are simultaneously equated in both the private sector and the NHS. The paper concludes by exploring the responsiveness of the equilibrium to various demand side and supply side shocks. PMID- 7780526 TI - On approximations in treatment costing. AB - As detailed costing may be a time-consuming and expensive exercise within an evaluation, economists will be conscious of the possibilities of taking short cuts. To explore the viability of such approaches in the context of acute care (the surgical treatment for colorectal cancer), we compare the results of a detailed costing study with reduced list costing and econometric estimation. We conclude, first, that use of a reduced list is likely to generate substantial research economies only at the expense of inaccuracy. Second, crude costing, based upon average costs of the specialty, is acceptable when the frame of reference is the aggregate. Such crude costing, however, is vulnerable to bias when specific sub-samples of patients are to be considered. Finally, total costs are predictable from a restricted list of cost and event variables, and with a high degree of accuracy, although ex ante specification of the functional form is problematic. PMID- 7780528 TI - The impact of nursing grade on the quality and outcome of nursing care. AB - The large industry which has grown up around the estimation of nursing requirements for a ward or for a hospital takes little account of variations in nursing skill; meanwhile nursing researchers tend to concentrate on the appropriate organisation of the nursing process to deliver best quality care. This paper, drawing on a Department of Health funded study, analyses the relation between skill mix of a group of nurses and the quality of care provided. Detailed data was collected on 15 wards at 7 sites on both the quality and outcome of care delivered by nurses of different grades, which allowed for analysis at several levels from a specific nurse-patient interaction to the shift sessions. The analysis shows a strong grade effect at the lowest level which is 'diluted' at each succeeding level of aggregation; there is also a strong ward effect at each of the lower levels of aggregation. The conclusion is simple; you pay for quality care. PMID- 7780529 TI - The demand for cigarettes in California and behavioural risk factors. AB - This study contributes to the understanding of the demand for cigarettes by taking into account the interdependence of smoking and other behavioural risk factors. Information on smoking and other behavioural risk factors including drinking, alcohol use, and obesity were obtained from the California Behavioural Risk Factor Survey for the period 1985-91. A monthly cigarette price index for California was constructed based on data obtained from the Bureau of Labor Statistics. A two-part model was used to examine separately the effect of price on the decision to be a smoker, and on the amount of cigarettes smoked by smokers. The overall price elasticity of cigarettes was estimated at -0.46, with a price elasticity of -0.33 for smoking participation and of -0.22 for the amount of cigarettes consumed by smokers. The inclusion of other behavioural risk factors reduced the estimated price elasticity for smoking participation substantially, but had no effect on the conditional price elasticity for the quantity of cigarettes smoked. PMID- 7780530 TI - Report cards or instrument panels: who needs what? AB - BACKGROUND: The report card movement in health care is a positive response to legitimate customer needs and requirements for comparative information on quality and costs. At the same time, providers have a legitimate concern about potential problems with gathering and using valid data in a prudent manner. Report cards have problems that often detract from their potentially constructive uses. In response to this concern, the authors propose that instrument panels--a newer concept in health care--compared to the static, judgmental image of report cards project an action-oriented, decision-making image. EXAMPLES: Descriptions are given of three types of instrument panels based on work in progress in the Dartmouth-Hitchcock health care system, a regional, integrated delivery system that serves the population of New Hampshire and parts of Vermont and Massachusetts: a 450-physician group practice (The Hitchcock Clinic), which provides more than one million visits per year in more than 25 locations; a tertiary health care facility (Mary Hitchcock Memorial Hospital) with more than 300,000 patient days; and prepaid health plan (Matthew Thornton Health Plan) with approximately 120,000 members. SUMMARY: It would be wise and efficient for providers to design instrument panel data collection systems that can feed directly into report cards, leading to the triple benefit of enhancing accuracy, reducing total costs, and increasing overall utility to both providers and their customers. PMID- 7780532 TI - Interdisciplinary integration for quality improvement: the Cleveland Veterans Affairs Medical Center Firm System. AB - BACKGROUND: Many of the characteristics of Firm Systems lend themselves to the application of principles of continuous quality improvement (CQI). A Firm System is defined as two or more parallel practices organized on the principle of continuity of relationships between patients and an interdisciplinary group of health care professionals and trainees. Firm Systems are organized around the care of the patient or customer and emphasize access, continuity, and quality of care. CASE STUDY: The Firm System was implemented at the Cleveland Veterans Affairs Medical Center (VAMC) not as a CQI initiative per se, but as an effort to coordinate the processes involved in the delivery of patient care. The primary goals of this implementation were to improve the quality of patient care, medical education, and health care research. The main strategy to deal with problems caused by uncoordinated care were to move from a departmental approach to an integrated interdisciplinary approach. This approach represented a paradigm shift within the organization that extended to planning, documentation, and the general work environment. Most important, the institution had leaders who were committed to the Firm System and willing to authorize resources to ensure its success. CONCLUSION: VA hospitals are ideal settings for Firm Systems because they provide longitudinal, comprehensive care with a centralized, prepaid payment mechanism, and they have well-developed information systems that allow the random assignment of patients to Firms. Recommendations to others interested in implementing Firm Systems include creation of a written plan that can gain general support; identification of resources needed for successful implementation; remembering that the patient is the most important customer, as well as that complex systems have many customers; monitoring of performance; and the importance of randomizing patients and providers. PMID- 7780533 TI - "Pathways to Performance": an interview with Jim Clemmer. Interview by Steven Berman. PMID- 7780534 TI - [Helicobacter pylori in children: many questions, few answers]. PMID- 7780535 TI - [Fetal growth deficiency: a hope!]. PMID- 7780531 TI - Reporting and using health plan performance information in Massachusetts. AB - BACKGROUND: In 1993, 27 corporate and government health care purchasers formed the Massachusetts Healthcare Purchaser Group (MHPG). Sixteen health plans submitted 1992 data on six clinical indicators-mental health inpatient days per patient and inpatient readmission, blood pressure screening, prenatal care, mammography screening, cesarean section (C-section) rates, and asthma admission rates-developed in an earlier pilot effort in response to the quality portion of MHPG's "Cost/Quality Challenge." DATA COLLECTION AND ANALYSIS: Detailed data specifications developed in the pilot to ensure uniform data collection were used, with a requested sample size for chart-reviewed measures of 220. A "clinically significant average range" was defined. Health plan performance was summarized for each indicator in a report released in March 1994. REPORTING OF CLINICAL INDICATOR RESULTS: For the six indicators, each plan had a unique pattern of variation from the average range. For prenatal care, mammography, and hypertension, many plans had opportunities for improvement. SURVEY OF PURCHASERS: Most of the purchasers MHPG surveyed in October 1994 about their assessment and use of the Cost/Quality Challenge Report found it useful. RESPONSES TO THE REPORT: To promote quality improvement activities among health plans, MHPG showed purchasers how to pursue performance issues with health plans, held a Best Practice Forum on C-section, and created a follow-up endeavor, the Coordinated Purchasing Initiative. SUMMARY AND CONCLUSIONS: In spite of potential problems posed by technical deficiencies, costs of data acquisition and quality efforts, and unintended effects of public reporting, purchaser/plan initiatives such as the Cost/Quality Challenge can provide valuable information to purchasers. PMID- 7780536 TI - [Genetics of epilepsy in children]. PMID- 7780537 TI - [Helicobacter pylori gastritis in children]. AB - BACKGROUND: The role of Helicobacter pylori in chronic gastric and duodenal ulcer disease has now been proven in adults as well as in children. MATERIAL AND METHODS: H pylori has been looked for during endoscopy in 130 children suffering from recurrent abdominal pain (78 patients) or other symptoms (52 patients). Biopsy samples were taken from the antrum and the fundus, and were examined for histology and bacteriology (Gram staining, urease test, culture). RESULTS: H pylori was found in 30 cases (H pylori+ group, medium age: 12 years) and was absent in the 100 other cases (H pylori- group, medium age: 6 years). H pylori was present in 27% of children suffering from recurrent abdominal pain and 17% of children with other symptoms. Epigastric location of the pain and vomiting were equally frequent in both groups. Endoscopic gastritis, often nodular, was noted in 60% of the cases in the H pylori+ group and in 46% in the H pylori- group (NS). Chronic gastritis was noted in 90% of the cases in the H pylori+ group, and in 32% of the cases in the H pylori- group (p < 0.01). Culture was positive in 27 out of 28 cases (97%) in the H pylori+ group, including 3 cases with negative histologic examination. Twenty-two children in the H pylori+ group were treated with amoxicillin and metronidazole. Endoscopy performed about 2 months later showed eradication of H pylori in 63% of the cases, associated with disappearance of histologic lesions in 6 out of 14 cases and of symptoms in 5 out of 7 cases. CONCLUSIONS: H pylori is associated with some pediatric cases of antral gastritis. Further studies are needed to determine the influence of its eradication on symptoms and the interest to search this pathology (by serology) in children suffering from chronic abdominal pain. PMID- 7780539 TI - [Measurement of peak expiratory flow in young children: comparison of four portable equipments]. AB - BACKGROUND: Peak expiratory flow (PEF) monitoring is seldom used in young children because peak flow meter normal values are needed for children less than 7 years old. POPULATION AND METHODS: PEF was measured in 152 non asthmatic school children, aged 2.9 to 14.5 years with four peak flow meters (Assess, DHS, Vitalograph, MiniWright). Calibration of these peak flow meters were performed with flows ranging from 100 to 700 l/min with a calibration syringe. RESULTS: Calibration demonstrated the excellent linearity of each device but there was a slight overestimation by DHS and MiniWright, and a slight underestimation by Vitalograph and Assess. PEF measured with the four devices was better linearly correlated with height (r = 0.72 to 0.77) than with age. Differences similar to calibration have been found between the four linear regressions. CONCLUSION: These results indicate that PEF can be used in young children less than 7 years old. It is necessary to always use the same peak flow meter for a child. PMID- 7780538 TI - [Failure of the treatment with antibiotics in severe Salmonella infections in children and use of quinolones]. AB - BACKGROUND: Quinolone antibiotics are effective in the treatment of Salmonella infections in adults. Their use in children is limited by their side-effects. POPULATION AND METHODS: Forty-two patients (21 girls and 21 boys), aged 1 month to 12 years (mean 3.3 yrs) were admitted from September 1991 to June 1993 for severe Salmonella infections. Criteria of severity were persistent diarrhea and fever for more than 3 days. Thirty-one of these patients were less than 5 years of age. Blood culture was positive in 7 out of 35 patients: culture of the stools was positive in all patients. Five of the 42 patients had presented an acute episode of Salmonella infection a few weeks earlier and had remained asymptomatic carriers until the new acute and severe episode of diarrhea. All patients were given usual antibiotics, mainly ampicillin, amoxicillin, trimethoprime sulfamethoxazole. Twenty-five of these patients were then given pefloxacin, 12 mg/kg/day, since the 5th day, for 7 days, because persistence of diarrhea and fever. RESULTS: Diarrhea and fever disappeared within less than 2 days in the group of patients given pefloxacin, even though in 6 patients the infecting Salmonella was in vitro resistant to beta-lactamins. Twenty % of patients remained asymptomatic carriers of Salmonella in the group treated by pefloxacin vs 47% in the group without it. There was no difference in species of Salmonella between both groups. None of the patients treated by pefloxacin developed side effects during the six months following its administration. CONCLUSIONS: Short treatment by pefloxacin may be an alternative choice for treating severe Salmonella infections in children. PMID- 7780540 TI - [Efficacy of oral administration of a micellaar solution of vitamin K during the neonatal period]. AB - BACKGROUND: Oral administration of vitamin K to neonates is quite satisfactory for preventing hemorrhagic disease of the newborn. The aim of this study is to test efficacy of a micellar solution of vitamin K at birth. POPULATION AND METHODS: Thirty full term infants, exclusively breast-fed during the first month of life, were included in this study. Seven of them (control group Cos) were given oral supplementation with 5 mg vitamin K1, cremophor; 15 other infants were given oral supplementation with 3 mg micellar solution of vitamin K1 (group MMos) and 7 were given an intramuscular injection of 1.5 mg micellar solution of vitamin K1 (group MMim). Prothrombin time activity and plasma vitamin K concentration were measured in the cord blood, 24 +/- 12 hours and 1 month after supplementation. RESULTS: No hemorrhage was seen and tolerance to vitamin K was good in the 3 groups. Mean prothrombin time activity was 54% in the cord blood, around 55% and 75%, 24 hrs and 1 month after supplementation, respectively; only one infant had low value (41%) by 1 month despite normal plasma vitamin K concentration. Two infants had low plasma vitamin K1 concentration by the second control despite normal prothrombin time activity; one belonged to the MMos group and the other to the Cos group. Mean values of plasma vitamin K1 concentration were higher by 1 month in the MMos group. CONCLUSION: A unique dose of micellar solution of vitamin K given orally at birth seems effective to prevent hemorrhagic disease. PMID- 7780541 TI - [Superior mesenteric artery syndrome]. AB - BACKGROUND: Early diagnosis of superior mesenteric artery syndrome, less frequent in children than in young adults, is improved by the use of ultrasonography and CT scan. CASE REPORT: An eleven year-old boy was admitted because he suffered from bilious vomiting for 24 hours. A diagnosis of superior mesenteric artery syndrome was made from the results of plain films of the abdomen, ultrasonography and roentgenograms after instillation of dilute barium solution. Diameter of the left renal vein appeared increased. The patient was given fractionated meals and placed in left lateral position. The CT scan performed 5 days later confirmed the diagnosis but did not show dilatation of the left renal vein. The patient is well one year later without treatment. Ultrasonography performed 3 hours after a meal showed similar findings to those seen in the acute phase. CONCLUSION: Abdominal scanning and ultrasound are valuable tools for diagnosis of such a syndrome. The diagnostic value of dilatation of the left renal vein remains to be determined. PMID- 7780542 TI - [Intraosseous infusion in children]. AB - BACKGROUND: Intravenous access in critically ill patients may be very difficult to obtain. The intraosseous route is an alternate way to administer fluids and drugs. CASE REPORT: A five month old infant was brought to the emergency department in profound hypovolemia requiring immediate tracheal intubation. A peripheral venous access was established and 35 ml of colloid were rapidly infused. Unfortunately, fluid extravasated and the intravenous line had to be removed. As further attempts to gain intravenous access were unsuccessful, an intraosseous needle was inserted into the left tibia 1 cm below the tibial tuberosity, and colloid and human albumin solution were infused rapidly, followed by 1.4% sodium bicarbonate. After ninety minutes of intraosseous rehydration, 2 peripheral venous lines were inserted, and the intraosseous needle was removed. Bacteriological and viral cultures were negative. Four days after admission, the child was discharged in good condition. CONCLUSIONS: Intraosseous infusion provides safe, rapid and reliable access to the circulation for administration of fluids and drugs in the critically ill child or during cardiac arrest. PMID- 7780543 TI - [Benign cutaneous lymphocytoma of the breast areola and Erythema chronicum migrans: a pathognomonic association of Lyme disease]. AB - BACKGROUND: Clinical manifestations of Lyme disease are mainly cutaneous, neurologic, cardiac and/or located joints. Some dermatologic manifestations are more specific. CASE REPORT: An eight year-old-girl was examined because she suffered from a nodular lesion located on the left breast areola which appeared 3 months earlier. This lesion was associated with an expanding erythematous annular lesion located on the anterior face of thorax and left axillary area, without any lymphadenopathy. The association of this cutaneous lymphocytoma and erythema chronicum migrans was suggestive of Borellia infection despite absence of previous tick bite. Serologic tests (indirect immunofluorescence) were negative, but both lesions disappeared within 2 weeks with ceftriaxone, 50 mg/kg/day. CONCLUSIONS: This association is pathognomonic of Lyme disease; serologic tests may be found negative in the early stages of disease. PMID- 7780544 TI - [Scimitar syndrome with anatomical or functional absence of the right pulmonary artery. Apropos of 4 cases]. AB - BACKGROUND: Scimitar syndrome is characterized by an anomalous pulmonary vein draining into the inferior vena cava and visible roentgenographically as a crescentic shadow of vascular density along the right border of the cardiac silhouette. The aim of this study is to report four cases associated with anatomical or functional absence of the right pulmonary artery. CASE REPORTS: Diagnosis of scimitar syndrome had been made in 4 patients aged 3, 10, 23 and 33 years. Pulmonary scintigraphy and/or CT scan detected the scimitar syndrome and the type of pulmonary and systemic vascularization. In all cases, the vascularization of the right lung did not originate from the pulmonary artery trunk but was supplied by systemic vessels arising from the abdominal aorta. The right pulmonary artery was vascularized a retro, against the stream, by the systemic vessels (two cases); alternatively, circulation into the right pulmonary artery resulted directly from the systemic vessels, this pulmonary artery being anatomically absent (two cases). Pulmonary arterial pressures were normal in all four cases and functional tolerance was good in three cases; repeated and severe hemoptysis required right pneumonectomy in the last patient. CONCLUSIONS: These four cases are compared to six other similar cases in the literature. Elegant and non invasive methods are now disposable to detect such a syndrome and to assess the type of pulmonary vascularization. PMID- 7780545 TI - [Corticosteroids: pharmacology and indications of short courses in pediatrics]. AB - The principle of short courses of corticosteroids (SCC), ie, courses of less than 2 weeks, is to use the potent anti-inflammatory effect of corticosteroids. The pharmacological and pathophysiological basis of this anti-inflammatory effect are presented. Because they represent a very peculiar strategy of treatment, intravenous bolus dosages of methylprednisolone are not discussed. As compared to cortisol, the synthetic corticosteroids used in SCC (ie, mainly prednisone, prednisolone and betamethazone) have a more potent anti-inflammatory activity, a reduced mineralocorticoid effect and a longer biological half-life. The main indications of SCC are laryngitis and acute asthma. SCC are also indicated in bacterial meningitis, in addition to antibiotherapy. Other indications are Henoch Schonlein purpura and intestinal inflammatory diseases. Adverse effects of SCC are uncommon. There are possible immunoallergic manifestations presenting mainly as skin reactions and sometimes as anaphylaxis. Abnormal psychological behaviour may be observed during the first 10 days of treatment. Few cases of ocular complications have been reported in adults, related to an increased intraocular pressure in patients with myopia or glaucoma. However, there is no evidence that SCC may cause gastric ulcer, nor that they may induce suppression of the adrenal function so that there is no need for a progressive decrease of the dosage when discontinuing the treatment. PMID- 7780546 TI - [Treatment of growth hormone deficiencies with growth hormone releasing hormone. Current status and perspectives]. AB - Results of clinical trials performed with human hypothalamic growth hormone releasing factor (GRF) are conflicting, but rather disappointing for most of them. Pulsatile administration of GRF has been found to increase growth hormone secretion as well as growth velocity, but is not convenient for practical use. All other routes and rhythms of administration lead only to sub-optimal results, and generally does not seem to procure an appropriate GRF bio-availability. Improvements are possible, particularly the development of agonists and new galenic forms with sustained release. Therapeutic approach with hexapeptides, or hexapeptides analogs, looks promising, but could be more complementary than competitive. PMID- 7780547 TI - [Vitamin D supplementation in pregnancy: a necessity. Committee for Nutrition]. AB - In septentrional countries without vitamin D supplementation of milk and dairy products, many pregnant women are vitamin D deficient. Consequently vitamin D deficiency is present in many newborn infants, which may lead to neonatal hypocalcemia and vitamin D deficient rickets. A prevention of vitamin D deficiency is therefore a necessity in pregnant women through a vitamin D supplementation. This can be done either by a daily supplementation of 400 IU during all pregnancy, or a daily supplementation of 1,000 IU during the third trimester, or by giving a unique dose of 100,000 to 200,000 IU during the seventh month of pregnancy. PMID- 7780548 TI - [Percutaneous endoscopic gastrostomy in pediatric practice]. AB - Percutaneous endoscopic gastrostomy (PEG) has become a good alternative to nasogastric tube feeding and surgical gastrostomy. The procedure requires two practitioners, one of them being an endoscopist. The technique can be performed either under local or general anesthesia, at bedside or in an operating room or endoscopic room, using a one step button or first setting of a catheter and secondly a button, by pull technique in which the button is pulled through esophagus or push technique were the button is pushed through the parietal wall. Its is used to deliver enteral nutriments in patients who need tube feeding. In paediatrics practice, morbidity rate related to PEG is less than 1% and morbidity less than 10%. PEG appears as a simple, safe, practical, esthetic and cheap procedure. PMID- 7780549 TI - [Myxedematous pericarditis in a child]. PMID- 7780550 TI - [Treatment of Streptococcus pneumoniae meningitis in infants]. PMID- 7780551 TI - [tPA thrombolytic treatment of aortic thromboses due to umbilical arterial catheterization in newborn infants]. PMID- 7780552 TI - [Exanthema in infants and children]. PMID- 7780553 TI - [Salivary cyst and gastroesophageal reflux in a newborn infant with syncope]. PMID- 7780554 TI - [Risks of drugs in pediatrics]. PMID- 7780555 TI - [Examination of children before entering elementary school]. PMID- 7780556 TI - [Histiocytosis in pediatrics]. PMID- 7780557 TI - [Mental retardation]. PMID- 7780558 TI - [Emergencies in infectious and parasitic pathology]. PMID- 7780559 TI - [Dermatology]. PMID- 7780560 TI - [Phakomatosis]. PMID- 7780561 TI - [The indications for LHRH analogs]. PMID- 7780562 TI - [Imaging in nephro-urology]. PMID- 7780563 TI - [Surveillance of premature infants during the first year]. PMID- 7780565 TI - Monocular elevation paresis caused by an oculomotor fascicular impairment. AB - A 54-year-old man developed an acquired monocular elevation paresis. Forced lid closure or oculocephalic reflexes failed to elevate the affected eye in contrast to the contralateral eye, which turned fully upward using either maneuver. A mass lesion compressing the lateral aspect of the right oculomotor nerve at the exit of the brainstem was found. The monocular elevation paresis in this patient reflects damage of the oculomotor nerve fascicles that supply the inferior oblique and superior rectus muscles. This case supports the accepted topographical fascicular arrangement of the oculomotor nerve, with the inferior oblique and superior rectus being the most lateral and caudal, and the pupilloconstrictor fibers and the inferior rectus being most medial and rostral. PMID- 7780564 TI - Microangiopathy of brain, retina, and inner ear. AB - Microangiopathy of brain, retina, and inner ear is a rare syndrome manifesting as arteriolar occlusions of the brain, retina, and inner ear, with resultant encephalopathy, visual, and hearing loss. Despite exhaustive laboratory examinations in these patients, no evidence of a systemic disease can be found. We treated and followed an adolescent with this disorder who initially presented with a branch retinal artery occlusion. A unique finding in this case was retinal vessel wall hyperfluorescence noted five days prior to retinal infarction. The patient developed recurrent branch artery occlusions, sensorineural hearing loss, and central nervous system infarctions despite anticoagulation and immunosuppressive treatment. PMID- 7780566 TI - Lack of differences among mitochondrial DNA in family members with Leber's hereditary optic neuropathy and differing visual outcomes. AB - Investigation of a maternal family of three generations of Leber's hereditary optic neuropathy (LHON) showed four affected and three unaffected individuals. Two of the four patients had recovered near-normal vision, one spontaneously, and one following treatment with idebenone, a quinol compound. One patient whose visual impairment persisted was a heavy consumer of alcohol and tobacco. Molecular genetic analysis of 12 known primary or secondary mutations in mitochondrial DNA (mtDNA) associated with LHON revealed only the 11778 mutation in a homoplasmic fashion with no secondary mutations. The variations in clinical outcome thus could not be explained by synergistically interacting secondary mutations in mtDNA. Environmental factors may play an etiologic role in the development of optic atrophy. PMID- 7780568 TI - Possible mechanisms for horizontal gaze deviation and lateropulsion in the lateral medullary syndrome. AB - We report a patient who developed conjugate horizontal gaze deviation and ipsipulsion of saccades from a lateral medullary infarction. Recent evidence suggests that the gaze deviation may result from increased inhibition of the ipsilateral vestibular nucleus and ipsipulsion of saccades from decreased excitation of the contralateral ocular premotor areas of the brainstem reticular formation. Interruption of the olivocerebellar pathways may account for both of these ocular motor abnormalities. PMID- 7780567 TI - Supranuclear eye movement dysfunction in mitochondrial myopathy with tRNA(LEU) mutation. AB - A patient with multiple neurological deficits and biopsy-proven mitochondrial myopathy with mutation of tRNA(LEU) at nucleotide 3243 was referred for eye movement evaluation. He had restricted range of voluntary motions in all directions and full range of eye movements on passive rotation of head while fixating a visual target. Eye movement recordings revealed decreased horizontal and vertical saccadic velocities and markedly decreased smooth pursuit gain in both directions. The vestibulo-ocular reflex showed gain abnormalities with many saccadic intrusions on the smooth reflex response. His brother, with similar mutation, was clinically asymptomatic. However, his eye movement recordings revealed slow horizontal saccadic velocities leftward and normal saccadic velocities rightward in both eyes as well as in upward and downward direction. Smooth pursuit and vestibulo-ocular reflexes were within normal limits. Although eye movement abnormalities are seen commonly in mitochondrial myopathies, the exact mechanism is not known. Our cases suggest supranuclear dysfunction as one of the mechanisms for ophthalmoparesis. PMID- 7780569 TI - Left dural to right cavernous sinus fistula. A case report. AB - Direct carotid-cavernous sinus fistulas that present with signs and symptoms contralateral to the arterial supply of the fistulas are not uncommon. We present a thoroughly documented case of a dural-cavernous sinus fistula with symptoms exclusively contralateral to the arterial source, a rarer entity. The patient presented with a red, proptotic right eye and a history of transient horizontal diplopia and a "feeling of fullness" in that eye. Magnetic resonance imaging (MRI) of the brain and orbits performed at another hospital had shown no abnormalities. Carotid angiography performed on the right side was normal; carotid angiography performed on the left side showed a dural-cavernous sinus fistula, with shunting from branches of the left external carotid artery directly to the right cavernous sinus. Orbital duplex color-flow sonography showed reverse flow in a dilated right superior ophthalmic vein. This unusual manifestation of a dural-cavernous sinus fistula offers insight into the pathophysiology of arteriovenous fistulas involving the cavernous sinus, and is a reminder that bilateral injections are required when performing carotid angiography to characterize these disorders. PMID- 7780570 TI - Invasive aspergillosis. A complication of treatment of temporal arteritis. AB - Temporal arteritis is a systemic necrotizing vasculitis for which the only effective treatment is systemic corticosteroids. A review of the literature suggests that there is a significant mortality rate in untreated patients but that those patients who receive adequate corticosteroid treatment rarely experience a reduced life expectancy. I had the opportunity to evaluate a patient with temporal arteritis who eventually died from disseminated aspergillosis 6 weeks after beginning corticosteroid treatment. A high index of suspicion for infections with opportunistic organisms should be maintained in patients with temporal arteritis receiving corticosteroids. PMID- 7780571 TI - Transient ictal cortical blindness during middle age. A case report and review of the literature. AB - We report a case of transient ictal cortical blindness in a 63-year-old woman. We reviewed the literature of all seizure-induced bilateral blindness. After careful evaluation of 44 cases, it was evident that the cases could be categorized into three groups with different etiologies, duration of blindness, and probable visual prognosis. Transient cortical blindness may occur with unilateral focal seizure or with bilateral seizure activity of the primary generalized type. Seizure-induced blindness may be ictal or postictal (Todd's) phenomenon or a permanent consequence following status epilepticus. Its duration varies between less than 1 minute to 4 months, or can be permanent. Our case of cortical blindness is related to new onset occipital epilepsy from a left occipital focus, and adds to the evidence that cortical blindness occasionally occurs as an uncommon manifestation of seizure. PMID- 7780572 TI - Adie's tonic pupil secondary to migraine. AB - A 46-year-old woman observed transient unilateral mydriasis during a classic migraine attack. One week later she experienced a similar episode after which anisocoria was persistent. Subsequent examination showed the clinical and pharmacologic features of a postganglionic parasympathetic paresis (Adie's tonic pupil). This case confirms the hypothesis that transient mydriasis accompanying migraine is due to interruption of parasympathetic innervation rather than sympathetic overactivity. PMID- 7780573 TI - Acute bilateral ophthalmoplegia secondary to metastatic prostatic carcinoma. Demonstration on magnetic resonance imaging. AB - We report an unusual case of acute bilateral ophthalmoplegia secondary to bilateral cavernous sinus metastasis from prostatic adenocarcinoma. The lesion was demonstrated with magnetic resonance imaging. PMID- 7780574 TI - The retrogeniculate sensory visual system and higher cortical function, 1993. PMID- 7780575 TI - Pain in anterior ischemic optic neuropathy. AB - PURPOSE: The diagnoses of both anterior ischemic optic neuropathy (AION) and optic neuritis are clinical ones with significant overlap of symptoms and signs. This study investigates the presence and character of pain at the onset of AION, in order to evaluate this symptom as a differentiating diagnostic feature between optic neuritis and AION. METHODS: Forty-one consecutive patients over 45 years of age with a clinical syndrome consistent with AION were questioned about the presence and character of associated pain. RESULTS: Pain was reported by 12% (5 of 41) of the patients with AION. This is contrasted with data compiled on 448 patients in the optic neuritis treatment trial, of whom 92.2% complained of pain. CONCLUSION: While there is overlap in the incidence and character of pain in AION and optic neuritis, its presence/absence remains a useful differentiating feature. PMID- 7780576 TI - High-performance liquid chromatography comparison of supercritical-fluid extraction and solvent extraction of microbial fermentation products. AB - The use of supercritical fluids for the extraction of biologically active compounds from the biomass of microbial fermentations has been compared with extraction using the organic solvents methanol and dichloromethane. Compounds representing a range of structural types were selected for investigation. All the extracts obtained were examined using reversed-phase high-performance liquid chromatography. The extractability of metabolites using unmodified and methanol modified supercritical-fluid carbon dioxide was examined in particular detail for six microbial metabolites: chaetoglobosin A, mycolutein, luteoreticulin, 7,8 dihydro-7,8-epoxy-1-hydroxy-3-hydroxymethyl-xanthone-8-carboxyl ic acid methyl ester, sydowinin B and elaiophylin. The extraction strength of supercritical fluid carbon dioxide alone appeared to be lower than that of dichloromethane. All the components of interest that were extractable with dichloromethane and methanol were also extractable with methanol-modified carbon dioxide. PMID- 7780577 TI - High-performance frontal analysis for the study of protein binding of troglitazone (CS-045) in albumin solution and in human plasma. AB - An on-line frontal analysis HPLC system was developed for the determination of the unbound concentration of troglitazone (CS-045), a new oral antidiabetic agent, in human serum albumin (HSA) solution and in human plasma. This system consists of a high-performance frontal analysis (HPFA) column, an extraction column, and an analytical column, which are connected via two switching valves. After the direct injection of the sample solution into the HPFA column, the drug was eluted as a zonal peak with a plateau region. The unbound drug concentration was determined as the drug concentration in the plateau. As low as 0.3 nM unbound CS-045 was determined with good reproducibility. It was found that CS-045 strongly binds with HSA, and the bound fraction in the 550 microM HSA solution was 99.93%, which was very close to that in human plasma (99.89%). The bound fractions were constant within the total drug concentration range of 1-10 microM in the HSA solution and 250 nM-10 microM in human plasma. PMID- 7780578 TI - Sensitive determination of the benzene metabolite S-phenylmercapturic acid in urine by high-performance liquid chromatography with fluorescence detection. AB - A method was developed for the determination of the specific benzene metabolite S phenylmercapturic acid in urine. The analyte is determined by HPLC with fluorescence detection after solid-phase extraction of urine with C18 material and hydrolysis followed by precolumn derivatization. The samples are separate by a column-switching method with a dual column system. As the method is highly sensitive (detection limit ca. 1 microgram/l), urinary S-phenylmercapturic acid concentrations for non-exposed persons (e.g., non-smokers) can also be measured precisely. PMID- 7780579 TI - Automated analysis of urinary catecholamines by high-performance liquid chromatography and on-line sample pretreatment. AB - A simple and automated solid-phase extraction for the selective and quantitative HPLC analysis of free catecholamines in urine is described. The urinary catecholamines react with diphenylboric acid, giving a complex at pH 8.5 which is strongly retained on a PLRP-S cartridge; elution is accomplished with the same mobile phase used for HPLC analysis. Separation is performed by ion-pair reversed phase HPLC, with sodium heptanesulphate as counter-ion, and a totally end-capped C18 analytical column. Quantitation is achieved with an electrochemical detector. A Spark Holland Prospekt system controls the on-line solid-phase extraction, preconcentration and direct elution to the LC column. Chromatography run-time is 10 min and the total time to process one urine sample is ca. 12 min. PMID- 7780580 TI - Complementary use of counter-current chromatography and hydroxyapatite chromatography for the separation of three main classes of lipoproteins from human serum. AB - High-density, low-density and very-low-density lipoproteins (HDLs, LDLs and VLDLs) were purified from human serum by the combined use of counter-current chromatography (CCC) and hydroxyapatite chromatography. Polymer-phase CCC of human serum using the cross-axis coil planet centrifuge yielded two lipoprotein fractions, one containing HDLs and LDLs and the other VLDLs and serum proteins. Each fraction was concentrated and subjected to hydroxyapatite chromatography to obtain three lipoprotein fractions, all free from serum proteins. Each lipoprotein was confirmed by agarose gel electrophoresis. PMID- 7780581 TI - Chromatography in DNA radiolabeling: hands-off automation using a robotic workstation. AB - The experiments described in the present paper were performed in order to determine whether the Biomek-1000 (Beckman Instruments, Fullerton, CA, USA) automated laboratory workstation can be used in a fully automated DNA labeling method followed by automated gravity-driven size exclusion purification of molecular probes. To this aim, we performed random oligodeoxyribonucleotide priming of a HIV-1 LTR probe that was used for molecular hybridization to Southern blotted polymerase chain reaction products. The results obtained demonstrate that the automatically labeled probe can be efficiently purified by automated and gravity-driven Sephadex G-50 chromatography, without any major changes in hybridization property. This robotic methodology can be used in several procedures employing radioisotope labeling. PMID- 7780582 TI - Analysis of all stratum corneum lipids by automated multiple development high performance thin-layer chromatography. AB - An optimized gradient enabling the separation of all stratum corneum lipids by automated multiple development on HPTLC plates is presented. An initial isocratic step separates sebum lipids. This is followed by a 25-step development using a gradient with a polarity range of methanol-water to hexane. Application to in vivo extracted and isolated stratum corneum lipids demonstrates the possible quantification of the lipid classes with a "one-experiment" separation. PMID- 7780583 TI - Influence of the injection technique on the thermal degradation of cocaine and its metabolites in gas chromatography. AB - Thermal degradation of some substances due to high temperature at the injection port and/or the type of injection technique used may limit the usefulness of gas chromatography with conventional detectors or coupled to mass spectrometry. To minimize thermal degradation of cocaine and its metabolites, chromatography was performed using two different insert liners and a cool on-column inlet. When using a packed liner, marked degradation of all compounds was observed. The degradation process was reduced by the use of an open liner and, when the cool on column inlet was employed, essentially no degradation occurred. PMID- 7780584 TI - High-performance liquid chromatographic-electrospray mass spectrometric determination of morphine and its 3- and 6-glucuronides: application to pharmacokinetic studies. AB - A rapid and selective assay of morphine and its 3- and 6-glucuronides in serum, based on high-performance liquid chromatography-electrospray mass spectrometry has been developed. The analytes and the internal standard, codeine or naltrexone, were subjected to solid-phase extraction, using ethyl solid-phase extraction columns, prior to chromatography. A reversed-phase column and a gradient mobile phase consisting of water and methanol were used. The mass spectrometer was operated in the selected-ion monitoring mode. The following ions were used: m/z 286 for morphine, m/z 300 for codeine, m/z 342 for naltrexone, and m/z 462 for morphine 3- and 6-glucuronides. The limit of quantitation observed with this method was 10 ng/ml morphine, 50 ng/ml morphine-6-glucuronide and 100 ng/ml morphine-3-glucuronide. The present method proved useful for the determination of serum levels of the parent drug and its metabolites in pain patients, heroin addicts and in morphine-treated mice. PMID- 7780585 TI - Simultaneous determination of ampicillin and metampicillin in biological fluids using high-performance liquid chromatography with column switching. AB - A new high-performance liquid chromatographic method with column switching has been developed for the simultaneous determination of metampicillin and its metabolite ampicillin in biological fluids. The plasma, urine and bile samples were injected onto a precolumn packed with LiChrosorb RP-8 (25-40 microns) after simple dilution with an internal standard solution in 0.05 M phosphate buffer (pH 7.0). The polar plasma components were washed out using 0.05 M phosphate buffer (pH 7.0). After valve switching, the concentrated drugs were eluted in the back flush mode and separated by an Ultracarb 5 ODS-30 column with a gradient system of acetonitrile-0.02 M phosphate buffer (pH 7.0) as the mobile phase. The method showed excellent precision, accuracy and speed with a detection limit of 0.1 microgram/ml. The total analysis time per sample was less than 40 min and the coefficients of variation for intra- and inter-assay were less than 5.1%. This method has been successfully applied to plasma, urine and bile samples from rats after intravenous injection of metampicillin. PMID- 7780586 TI - Screening and determination of beta-blockers, narcotic analgesics and stimulants in urine by high-performance liquid chromatography with column switching. AB - A fast method is described for the screening of eleven beta-blockers, two narcotic analgesics and two stimulants in urine by HPLC with column switching. The urine sample (100 microliters), buffered to pH 9-9.5, is injected onto a short extraction column packed with CN stationary phase. The extraction column is flushed with water for 2.5 min to elute polar matrix components to waste. The retained components are then backflushed by means of a six-port valve onto the ODS analytical column where they are separated. Phosphate buffer pH 3.0 and acetonitrile were used as mobile phase. Gradient elution was applied in the screening method to improve separation. Detection was performed with a diode array detector at 220, 235 and 300 nm. Recoveries were near 100%, precision was excellent and sensitivity about 0.25 micrograms/l. To speed up the quantitative analysis, the same method but with isocratic elution was successfully applied to the determination of acebutolol and metoprolol in urine samples collected 4 h after administration of the compounds as single doses. PMID- 7780587 TI - Simultaneous determination of terbinafine (Lamisil) and five metabolites in human plasma and urine by high-performance liquid chromatography using on-line solid phase extraction. AB - The antimycotic agent terbinafine (Lamisil) and five of its main metabolites were determined simultaneously in human plasma and urine samples by an isocratic HPLC method. The compounds were separated on a phenyl column following on-line solid phase sample clean-up with a column-switching device. Terbinafine and its metabolites were detected by monitoring the column effluent with UV light at a wavelength of 224 nm. The linear range in plasma was assessed between 0 and 2500 ng/ml for the parent drug and metabolites V, IV and I. The linear response of metabolites III and II was assessed between 0 and 1250 ng/ml. In urine, linearity was assessed between 0 and 10,000 ng/ml for metabolites V, IV, III, II and between 0 and 1000 ng/ml for the parent drug and metabolite I. Quantification limits based on a C.V. < or = 20% and a bias < or = +/- 20% ranged from 20 to 500 ng/ml depending on the compound and the matrix. Inter-day and intra-day variations were similar indicating the ruggedness of the two methods. Due to the considerable differences in hydrophobicity between the compounds, extraction efficiencies ranged from 55 to 100%. Both methods were found to be reproducible and sufficiently sensitive for the evaluation of metabolite pharmacokinetics. PMID- 7780588 TI - Manual and automated determination of 1-beta-D-arabinofuranosyl-E-5-(2 bromovinyl)uracil and its metabolite (E)-5-(2-bromovinyl)uracil in urine. AB - This paper describes the determination of 1-beta-D-arabinofuranosyl-E-5-(2 bromovinyl)uracil in urine. The method involves sample clean-up by liquid-liquid extraction with ethyl acetate followed by high-performance liquid chromatographic (HPLC) analysis. The sample preparation may be performed either manually or automatically using a Zymark Py-robotic system. The chloro analog of the parent compound, CV-araU, is used as the internal standard. As low as 0.1 microgram of analyte per ml of urine can be measured. This sensitivity is adequate for pharmacokinetic studies but could be improved quite easily if necessary. PMID- 7780589 TI - High-performance liquid chromatographic assay for 3'-amino-3'-deoxythymidine in plasma, with 9-fluorenyl methyl chloroformate as the derivatization agent. AB - We have developed a sensitive high-performance liquid chromatographic assay for the determination of the zidovudine metabolite 3'-amino-3'-deoxythimidine (AMT) using fluorescence and sensitivity in the picomolar range. Plasma was diluted with 0.05 M sodium phosphate buffer pH 7.2 and subsequently prepared for analysis using solid-phase extraction. AMT was derivatized with 9-fluorenyl methylchloroformate and chromatographed using a reversed-phase system. The mobile phase consisted of acetonitrile-0.01 M potassium phosphate buffer (pH 7) (32.68, v/v). The fluorescence of the column effluent was monitored at 262 nm (excitation) and 306 nm (emission). Good resolution of AMT from endogenous plasma components was obtained. Within- and between-day variability was less than 10%. The limit of quantitation was 0.9 microgram/l. The assay was successfully applied to the determination of AMT in human plasma and in plasma of mice treated with zidovudine. PMID- 7780590 TI - High-performance liquid chromatographic procedures for the quantitative determination of paclitaxel (Taxol) in human urine. AB - A reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for the quantitative determination of paclitaxel in human urine. A comparison is made between solid-phase extraction (SPE) and liquid liquid extraction (LLE) as sample pretreatment. The HPLC system consists of an APEX octyl analytical column and acetonitrile-methanol-0.2 microM ammonium acetate buffer pH 5 (4:1:5, v/v) as the mobile phase. Detection is performed by UV absorbance measurement at 227 nm. The SPE procedure involves extraction on Cyano Bond Elut columns. n-Butylchloride is the organic extraction fluid used for the LLE. The recoveries of paclitaxel in human urine are 79 and 75% for SPE and LLE, respectively. The accuracy for the LLE and SPE sample pretreatment procedures is 100.4 and 104.9%, respectively, at a 5 micrograms/ml drug concentration. The lower limit of quantitation is 0.01 microgram/ml for SPE and 0.25 microgram/ml for LLE. Stability data of paclitaxel in human urine are also presented. PMID- 7780591 TI - Determination of paclitaxel and metabolites in mouse plasma, tissues, urine and faeces by semi-automated reversed-phase high-performance liquid chromatography. AB - We have developed and validated a sensitive and selective assay for the quantification of paclitaxel and its metabolites 6 alpha, 3'-p dihydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6 alpha-hydroxypaclitaxel in plasma, tissue, urine and faeces specimens of mice. Tissue and faeces were homogenized (approximately 0.1-0.2 g/ml) in bovine serum albumin (40 g/l) in water, and urine was diluted (1:5, v/v) in blank human plasma. Sample pretreatment involved liquid-liquid extraction of 200-1000 microliters of sample with diethyl ether followed by automated solid-phase extraction using cyano Bond Elut columns. 2'-Methylpaclitaxel was used as internal standard. The overall recovery of the sample pretreatment procedure ranged from 76 to 85%. In plasma, the lower limit of detection (LOD) and the lower limit of quantitation (LLQ) are 15 and 25 ng/ml, respectively, using 200 microliters of sample. In tissues, faeces and urine the LLQs are 25-100 ng/g, 125 ng/g and 25 ng/ml, respectively, using 1000 microliters (faeces: 200 microliters) of homogenized or diluted sample. The concentrations in the various biological matrices, for validation procedures spiked with known amounts of the test compounds, are read from calibration curves constructed in blank human plasma in the range 25-100,000 ng/ml for paclitaxel and 25-500 ng/ml for the metabolites. The accuracy and precision of the assay fall within the generally accepted criteria for bio analytical assays. PMID- 7780592 TI - Stereospecific high-performance liquid chromatographic determination of an S(-) benzopyran methyl ester derivative (CGP 50 068), its (-)-carboxylic acid metabolite (CGP 55 461) and the related (+)-enantiomer (CGP 54 228) in human and dog plasma. AB - The simultaneous determination of CGP 50 068, S(-)-enantiomer (I), its (-) carboxylic acid metabolite CGP 55 461 (II) and the related (+)-enantiomer CGP 54 228 (III) by stereospecific high-performance liquid chromatography, in human plasma, is described. The three compounds and racemic acebutolol, used as internal standard, were isolated from plasma by liquid-solid extraction on disposable C18 columns. The resolution and determination of I and the two carboxylic acid enantiomers were achieved by direct chromatography using a Chiral AGP column refrigerated at 5 degrees C. The mobile phase was tetrabutylammonium iodide in a pH 7 phosphate buffer solution used at a constant flow-rate of 0.5 ml/min. The UV detection wavelength was set at 270 nm. The reproducibility and accuracy of the method were found to be suitable over the concentration range 0.56-28.0 mumol/l for II and III and 2.0-26.7 mumol/l for I. PMID- 7780593 TI - Determination of a new fluoroquinolone antimicrobial agent, (S)-10-[(S)-(8-amino 6-azaspiro d3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3 de][1,4]benzoxazine-6- carboxylic acid hemihydrate, DV-7751a, in human serum and urine using solid-phase extraction and high-performance liquid chromatography with fluorescence detection. AB - A high-performance liquid chromatographic method for the determination of a new fluoroquinolone antimicrobial agent, (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6 yl)]-9-fluoro-2,3- dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6 carboxylic acid hemihydrate (DV-7751a, I) in human serum and urine has been developed. Compound I and the internal standard were extracted from serum and urine by means of Bond Elut C8 LRC column. The extracts were chromatographed on a reversed-phase Inertsil ODS-2 column using tetrahydrofuran-50 mM KH2PO4 (pH2)-1 M ammonium acetate (19:81:1, v/v) as the mobile phase at a flow-rate of 1.0 ml/min. Fluorescence detection at an excitation wavelength of 305 nm and an emission wavelength of 530 nm resulted in a limit of quantitation of 0.0098 microgram/ml for serum and 0.098 microgram/ml for urine. The method showed satisfactory sensitivity, precision, accuracy, recovery and selectivity. Stability studies showed that I was stable in serum and urine for at least 1 month at -20 degrees C and for at least 48 h at room temperature. PMID- 7780594 TI - High-performance liquid chromatographic assay for the determination of the novel etoposide derivative dimethylaminoetoposide (NK611) and its metabolites in urine of cancer patients. AB - A simple, reproducible and specific urine assay for the novel epipodophyllotoxin derivative dimethylaminoetoposide (NK611, I) its picro form (III), the N-demethyl metabolite (II) and its picro form (IV) is reported. The method involves the addition of Pr-NK611 as internal standard, chloroform extraction and HPLC separation on a Nova-Pak C18 column with a mobile phase of acetonitrile-0.05 M KH2PO4 (pH 6.4) (23:77, v/v). UV detection was used with absorbance monitored at 205 nm and the limit of quantification was 100 ng/ml. The intra- and inter-day precisions were within the ranges 1.1-3.4% and 1.9-2.4% for all analytes and the accuracy was 101-107%. The extraction recovery was more than 88% for I, II and IV and more than 83% for III. The assay is applicable to the urinary monitoring of I IV in clinical pharmacokinetic investigations. PMID- 7780596 TI - Determination of total plasma homocysteine and related aminothiols by gas chromatography with flame photometric detection. AB - A selective and sensitive method for the determination of total homocysteine (Hcy) and related aminothiols, such as cysteine (Cys) and cysteinylglycine (CysGly), in plasma samples by gas chromatography (GC) has been developed. After reduction of the sample with sodium borohydride, the liberated Hcy and other aminothiols were converted to their N,S-diisopropoxycarbonyl methyl ester derivatives and measured by GC with flame photometric detection using a DB-17 capillary column. The calibration curves were linear over the range 0.5-10 nmol for Hcy and CysGly, and over the range 5-100 nmol for Cys, and the correlation coefficients were above 0.996. Using this method, total plasma Hcy, Cys and CysGly could be directly analysed without prior clean-up of the sample and without any interference from coexisting substances. Overall recoveries of Hcy and other aminothiols added to plasma samples were 95-106%. Analytical results for the determination of total plasma Hcy, Cys and CysGly from normal subjects are presented. PMID- 7780595 TI - Determination of portal short-chain fatty acids in rats fed various dietary fibers by capillary gas chromatography. AB - A simple, rapid and sensitive capillary gas chromatographic method was investigated to measure portal short-chain fatty acids (SCFAs). A 20-microliters sample of portal plasma was denatured with sulfosalicylic acid and then extracted with diethyl ether before the removal of protein precipitate. The resultant extract was concentrated by a transfer to 50 microliters of 0.2 M NaOH, thus avoiding tedious further concentration steps. This reduced the sample volume to one-fourth. Since the ratio of acetic acid, a major SCFA, to other acids varies widely, ranging from 10-fold to 100-fold, acrylic and methacrylic acids were used as internal standards to simultaneously measure SCFAs having a carbon number of 2 6. As a result, good recovery (90.38-103.17%) and reproducibility (coefficient of variation 0.83-8.85%) were observed over a wide range. Furthermore, portal SCFAs in rats fed various dietary fibers were determined by the present method. We showed that the amounts not only of the major acids such as acetic acid and propionic acid, but also of the minor fermented products such as n-valeric acid and n-caproic acid, could be significantly changed by dietary manipulation. Thus, the present method is simple and reliable, and requires only a small amount of sample. PMID- 7780597 TI - Capillary liquid chromatography-fast atom bombardment mass spectrometry using a high-resolving cation exchanger, based on a continuous chromatographic matrix. Application to studies on neuropeptide peptidases. AB - Hyphenated mass spectrometric techniques such as LC-MS are advantageous over standard MS methods, because they provide increased sensitivity and minimize signal suppression by other compounds present in the reaction mixture. Recently, we have introduced so-called continuous beds, and applied this technique to prepare a 0.32 mm I.D. cation-exchange capillary column, in order to separate the reaction product substance P(1-7) after proteolytic cleavage of substance P by an endopeptidase recovered from human cerebrospinal fluid. The use of a volatile buffer for elution provides very good flow stability. Ion-exchange microcolumns may be particularly useful for the separation of those peptides that co-elute in reversed-phase chromatography because the separation mechanisms of these two methods are different. PMID- 7780598 TI - Analysis of bile acids and their conjugates using high-pH anion-exchange chromatography with pulsed amperometric detection. AB - Bile acids and their conjugated forms may be separated by anion-exchange chromatography in alkaline media (0.9 M sodium acetate, 0.1 M sodium hydroxide, 15% v/v acetonitrile) on a CarboPac PA-100 column. The effluent was monitored at high sensitivity, with detection limits of less than 10 microM, using a pulsed amperometric detector. Free bile acids and their glyco- and tauro-conjugated forms were separated and detected within 40 min under isocratic conditions. PMID- 7780599 TI - Rapid determination of dabsylated hydroxyproline from cultured cells by reversed phase high-performance liquid chromatography. AB - A high-performance liquid chromatographic method was modified for the determination of hydroxyproline in cultured cells derived from rat liver. First, the primary amino group in the cell hydrolysate was blocked with o phthalaldehyde, then the secondary amino group was derivatized with 4 dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride). The dabsylated sample was treated with ethyl acetate to obtain a simple chromatographic elution profile of the cell hydrolysate. Dabsylhydroxyproline and proline were separated from other compounds by high-performance liquid chromatography in the gradient elution mode, and eluted at 4.71 and 8.00 min, respectively. The method was applied to the determination of hydroxyproline contained in cultured cells, the result being 25.4 +/- 3.6 pmol/microgram. PMID- 7780600 TI - Rapid and specific high-performance liquid chromatographic method for the determination of iodide in urine. AB - A rapid and specific method for the determination of iodide in urine by high performance liquid chromatography on an anion-exchange column with electrochemical detection is described. The assay is reproducible as judged by the coefficient of variation of less than 4% at all concentrations used. The limit of detection was 0.1 mumol, and the calibration graph was linear for concentrations between 0.1 and 200 mumol. Using this method, healthy volunteers were found to excrete 69 +/- 39 mumol of iodide per mole of creatinine. PMID- 7780601 TI - Selective elution and purification of living Trichomonas vaginalis using gravitational field-flow fractionation. AB - Gravitational field-flow fractionation is one of the simplest separation methods for biological materials. Its potential in parasitology is demonstrated for Trichomonas vaginalis, a parasite responsible for one of the most widespread sexually transmitted diseases. It was observed that this unicellular parasite can be purified in a culture medium with a recovery of 85% for the living trophozoites. The parasite retention characteristics were different when motile living and non-motile dead cells were eluted, motile cells being less retained than the non-motile cells. PMID- 7780602 TI - Gas chromatographic determination of methamphetamine and its metabolite amphetamine in human plasma and urine following conversion to N-propyl derivatives. AB - A gas chromatographic method for the simultaneous determination of methamphetamine and its metabolite amphetamine in human plasma and urine is described. The method utilizes reductive alkylation with propionaldehyde and sodium borohydride to produce N-propyl derivatives, which have excellent chromatographic properties. Structural analogs of the analytes, p methylmethamphetamine and p-methylamphetamine, are used as internal standards. The method has good precision and accuracy for concentrations ranging from less than 10 ng/ml to 5000 ng/ml and has been used to measure plasma concentrations as part of a pharmacokinetic/pharmacodynamic study of methamphetamine in humans. PMID- 7780603 TI - Rapid identification of 4-hydroxy-2-alkylquinolines produced by Pseudomonas aeruginosa using gas chromatography-electron-capture mass spectrometry. AB - The 4-hydroxy-2-alkylquinolines and their N-oxides are secondary metabolites produced by Pseudomonas aeruginosa which inhibit the growth of a number of Gram positive organisms including Staphylococcus aureus. To facilitate the identification of these compounds in biological fluids, we have developed a rapid profiling system based on gas chromatography-electron-capture mass spectrometry of the O-bistrifluoromethylbenzoyl derivatives. Using the technique, over twenty hydroxyalkylquinolines have been identified from a culture obtained from a strain of P. aeruginosa obtained from a patient with severe bronchiectasis. PMID- 7780604 TI - High-performance liquid chromatographic method for the determination of budesonide in bronchoalveolar lavage of asthmatic patients. AB - A simple, sensitive and selective method for the determination of budesonide in bronchoalveolar lavage (BAL) using high-performance liquid chromatography (HPLC) with UV detection was developed. BAL samples were extracted twice with methylene chloride, the extracts were centrifuged and the organic layer separated and dried under nitrogen. The samples were reconstituted in the mobile phase and 80 microliters were injected on to a Spherisorb ODS column with UV absorbance detection at 250 nm. The mobile phase was methanol-aqueous buffer (69:31, v/v). Inter-assay coefficients of variation were measured at 7.81 and 500 ng/ml with ranges of 0.89-7.31%. Average recoveries were 97% or greater. This method was successfully implemented for the analysis of BAL from asthmatics, in order to establish the amount of budesonide available to the lung and to investigate the efficacy of inhaler systems. Patients (n = 9) inhaled four puffs of 200 micrograms of budesonide and BAL was performed 10 min after the last inhalation. Only four BAL out of the nine presented detectable amounts of budesonide. The concentrations in BAL in these four patients were 13.44-84.18 ng/ml, corresponding to total amounts of 0.847-7.997 micrograms. PMID- 7780605 TI - Reversed-phase high performance liquid chromatographic determination of cyproheptadine from urine by solid-phase extraction. AB - A simple, sensitive and reliable high-performance liquid chromatographic method for the determination of cyproheptadine in urine by solid-phase extraction (SPE) has been developed. The sample matrix was passed through a pre-conditioned C18 cartridge, washed with methanol-water solution (4:1) and eluted with methanol. The methanolic solution was evaporated to dryness, reconstituted with methanol and chromatographed using a C18 reversed-phase column. The mobile phase consisted of acetate buffer (constant ionic strength of 0.005 I)-methanol (56:44, v/v). Detection was performed at 254 nm with the sensitivity set at 0.002 AUFS. Concentrations as low as 50 ng/ml could be quantitatively determined by an external standard method and the overall recovery was found to be 76.16%, whereas the limit of detection was estimated as 15 ng/ml. PMID- 7780606 TI - Sensitive high-performance liquid chromatographic method for the determination of methyl N-[5-[[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl d carbamate in rat blood. AB - A sensitive high-performance liquid chromatographic assay has been developed and validated for the determination of methyl N-[5-[[4-(2-pyridinyl)-1 piperazinyl]carbonyl]-1H-benzimidazol-2-y l d carbamate (CDRI compound 81/470) in normal rat blood. The method described herein is simple, with improved selectivity and sensitivity over a previously reported HPLC method. The limit of quantitation is 10 ng/ml (method 1) and 2.5 ng/ml (method 2) in blood, as compared with 40 ng/ml for the previous method. The standard curve in blood is linear over the concentration range 10-1000 ng/ml in method 1 and 2.5-1000 ng/ml in method 2 and the extraction recovery is higher than 80% for both methods. PMID- 7780607 TI - Evolving strategies for the management of non-palpable breast abnormalities. AB - Increased public and professional awareness has resulted in more women obtaining mammograms. As a result, the surgeon is often called on to diagnose and treat occult breast lesions. The development of new diagnostic modalities has changed the way such breast lesions are approached. Management decisions are made in the context of new pressures applied by the growing managed care imperative and increased mediocolegal exposure. In this review, we establish guidelines for the management of non-palpable breast abnormalities that place the welfare of the patient first. PMID- 7780608 TI - The value of endorectal ultrasonography in the follow-up of intracavitary radiation treated early rectal cancer. AB - In selected patients with early rectal cancer, intracavitary radiation is a successful treatment. Endorectal ultrasound has proved an accurate method for staging and selecting such cancers for treatment. The value of endorectal ultrasound in the follow-up of patients with intracavitary radiation has not been previously assessed. Between 1989 and 1991, 30 patients treated at the Hamilton Regional Cancer Centre with intracavitary radiation were assessed by endorectal ultrasound. The mean age was 65 +/- 12 years with a range of 37-78 years. There were 17 males and 13 females. All patients were treated with curative intent. The dose of radiation administered was 8963 +/- 1506 cGy over 3.5 +/- 0.7 fractions. No patient received supplemental iridium implantation. Thirty-seven endorectal ultrasounds were carried out in 30 of the intracavitary radiation treated patients. Clinical findings (digital, sigmoidoscopic, and histology) were compared with the radiologist's interpretation of the endorectal ultrasounds. Using a 2 x 2 table accepting the clinical findings as the 'Gold Standard', the sensitivity of endorectal ultrasound was 71%, the specificity 61%, the positive predictive value 53%, the negative predictive value 78% with an overall accuracy of 75%. We conclude that endorectal ultrasound in the routine follow-up of patients treated with intracavitary radiotherapy for carcinoma of the rectum is questionable. PMID- 7780609 TI - The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer. AB - Studies suggest that the interplay between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), is an important mediator of tumour invasion and metastasis. Using immunohistochemistry, 40 specimens of colorectal cancer were examined for the presence of TIMP-1 and the MMPs, stromelysin, gelatinases A and B and interstitial collagenase. Neither enzyme nor TIMP-1 was detected in histologically normal mucosa. Within malignant tissue, stromelysin and gelatinase A were conspicuously absent in tumour cells but were immunolocalized to the extracellular matrix and for gelatinase A also to peritumoural fibroblast-like cells. Gelatinase B was confined to polymorphonuclear leucocytes. Interstitial collagenase was not identified. TIMP-1 was present in only three of the 40 tumours within the malignant stroma. These observations suggest that the mesenchymal elements of colorectal carcinomas, by acting as a source of MMPs and TIMPs, may modulate tumour invasion. PMID- 7780611 TI - Symptomatic outcome following resection of gastric cancer. AB - The extent to which the different resections relieve the symptoms of gastric cancer is poorly defined. The symptoms of 57 consecutive patients undergoing standard resection of gastric adenocarcinoma by oesophagogastrectomy (n = 19), total gastrectomy [16] or partial gastrectomy [22] were studied prospectively. Common symptoms were relieved in 80% of cases and this was independent of tumour stage. Symptoms were significantly more frequent after total gastrectomy than after partial gastrectomy or oesophagogastrectomy, the difference being attributable principally to the development of new symptoms after total gastrectomy. While abdominal pain, nausea and vomiting were largely relieved by resection, dyspepsia or dysphagia worsened in 31% of patients following surgery, especially total gastrectomy (P < 0.05). Resection relieves the symptoms of gastric cancer adequately but outcome is influenced by operation type. As total gastrectomy gives a poorer symptomatic outcome, it should be avoided when the performance of an alternative procedure does not compromise established principles of resection. PMID- 7780610 TI - Protective role of lactulose in intestinal carcinogenesis. AB - Primary bile acids are converted to carcinogenic secondary bile acids by colonic bacteria when the colonic pH is high. Therefore acidification of the luminal contents may reduce the cancer risk. The ability of lactulose to reduce colonic pH, secondary bile acid production, mucosa crypt cell production rate and tumour formation was measured in a rat model of intestinal carcinogenesis. Eighty Wistar rats were divided into four groups receiving normal diet alone or with lactulose, azoxymethane or both azoxymethane and lactulose. The addition of lactulose was associated with a significant fall in small intestinal and colonic pH. Lactulose was associated with a sharp rise in the secondary to primary bile acid ratio. The crypt cell production rate fell significantly with lactulose. The addition of lactulose was associated with a significantly reduced tumour yield in small intestine but not in colon. Lactulose therefore can reduce this is of no value in humans at risk of developing colorectal carcinoma. PMID- 7780612 TI - In vitro stimulation of ovarian tumour-associated lymphocytes with a peptide derived from HER2/neu induces cytotoxicity against autologous tumour. AB - The proto-oncogene HER2/neu encodes for a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor (EGF) receptor. We have previously shown a correlation between HER2/neu expression and the level of in vitro cytotoxicity of tumour-associated lymphocytes (TAL) versus autologous tumour. In addition, we have recently demonstrated that tumour-associated cytotoxic T-lymphocytes (CTL) from ovarian and breast cancer patients can recognize a HER2/neu derived peptide epitope when presented in the context of HLA A2. Since repeated tumour stimulation of CTL enhances both proliferation and cytotoxicity against autologous tumour, we hypothesized that repeated peptide antigen stimulation would have a similar effect. To be therapeutically useful, the peptide antigen must meet the following conditions: (1) the peptide must be immunogenic and cause a proliferation of CTL to adequate therapeutic numbers, and (2) the peptide-specific CTL which are generated must be cytotoxic against autologous tumour. To test our hypothesis, T-lymphocytes isolated from the ascites of four consecutive HER2/neu+ ovarian cancer patients were initially stimulated with solid phase anti-CD3 antibody and divided into three groups: (1) treatment with recombinant interleukin-2 (IL-2) alone, (2) IL-2 plus weekly stimulation with irradiated autologous tumour cells, and (3) IL-2 plus weekly stimulation with a HER2/neu derived peptide. Peptide-stimulated and tumour stimulated CTL showed similar increases in proliferation with both groups consistently reaching therapeutic numbers. Peptide-stimulated CTL demonstrated significantly enhanced cytotoxicity against autologous tumour in 4-h chromium release assays as compared to the IL-2 alone group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780613 TI - The relationship between the immunodetection of transforming growth factor-beta in lung adenocarcinoma and longer survival rates. AB - We immunohistochemically examined the expression of transforming growth factor beta (TGF-beta) on tissue specimens from primary 124 human lung adenocarcinoma, using a polyclonal antibody. The overall mean immunoreactivity of TGF-beta was 25.7 +/- 22.9, therefore we separated patients into two groups according to their mean immunoreactivity. There were 59 (48%) with a high TGF-beta and 65 (52%) with a low TGF-beta. No correlation was observed between the expression of TGF-beta and clinicopathological factors except for degree of differentiation. The 5-year survival rates of patients with high and low TGF-beta were 71% and 37%, respectively (P < 0.05). A multivariate analysis using the Cox life table regression model showed TGF-beta to be a significantly independent factor. We thus concluded, based on our findings, that the expression of TGF-beta was found to be related to a better prognosis. Therefore, estimating the negative cell proliferation activity induced by TGF-beta on immunohistochemical technique is considered to be useful for determining the patients' prognosis in cases of lung adenocarcinoma. PMID- 7780614 TI - Electrophysiology of atrial fibrillation. PMID- 7780615 TI - Therapy for atrial fibrillation: control of the ventricular response and prevention of recurrence. PMID- 7780617 TI - Surgery for atrial fibrillation. PMID- 7780616 TI - Radiofrequency catheter ablation for atrial fibrillation. PMID- 7780618 TI - Anticoagulation/platelet inhibition for atrial fibrillation. PMID- 7780619 TI - Determinants of transmitral inflow pattern 10-14 days after acute myocardial infarction. AB - AIM: The administration of thrombolytic therapy after an acute myocardial infarction can reduce the size of the infarct and improve left ventricular function. We used pulsed Doppler to assess left ventricular diastolic function after an acute myocardial infarction in patients treated with recombinant tissue plasminogen activator (rTPA). PATIENTS AND METHODS: We studied 104 patients after an acute myocardial infarction, 48 treated with a placebo and 56 with rTPA. They were compared with 36 age-matched controls. The Doppler parameters measured included the early peak in diastolic flow velocity, the peak during atrial contraction, the atrial: early ratio, mean deceleration, deceleration time, and half-filling fraction. Doppler parameters for large and small infarct sizes were compared. RESULTS: The Doppler parameters did not differ between treatment groups. Compared with the normal controls, significant differences were observed in both treatment groups for the early peak (placebo P < 0.05; rTPA P < 0.001), the atrial: early ratio (placebo P < 0.05; rTPA P < 0.01), and the half-filling fraction (P < 0.001 for both). In patients with large infarcts, the atrial peak was depressed (P = 0.008). Multivariate analysis showed that end-diastolic pressure, age, end-systolic volume, and regional wall motion parameters were major predictors of Doppler parameters. PMID- 7780620 TI - Psychosocial factors predict medical outcome following a first myocardial infarction. Working Group on Cardiac Rehabilitation of the Swiss Society of Cardiology. AB - BACKGROUND: The aim of this study was to identify psychosocial variables that, in addition to known medical factors, predict the long-term outcome after a first myocardial infarction. PATIENTS AND METHODS: The study population consisted of 222 men aged 30-60 years who entered an inpatient rehabilitation program a mean of 7 weeks after a first myocardial infarction. Medical data and completed questionnaires for psychosocial variables were obtained from the patients and their family physicians at entry to the rehabilitation center and 1 year later. Further data, including answers to a detailed questionnaire, were collected at the beginning of rehabilitation and after one year; this follow-up was 99% complete. RESULTS: The 1-year mortality was 2.2%, the reinfarction rate 1.8%, hospital readmissions for cardiac reasons occurred in 25%, and 13% of the patients underwent a subsequent revascularization procedure. At baseline and after 1 year, respectively, 84 and 83% of the patients were asymptomatic. A poor medical outcome, defined as death, reinfarction, severe symptoms or poor exercise capacity, was seen in 9% of the patients. The most important physiological predictors for an unfavourable medical outcome, found in bivariate and multivariate analyses, were age, severity of infarction, and major coronary risk factors. In addition, some of the psychosocial variables were significantly related to a poor medical outcome: lack of a stable partnership, high work load, poor general well-being with multiple chronic non-specific health complaints, and a low external locus of control (failure to identify disease-promoting factors within own surroundings or lifestyle). CONCLUSIONS: The medical course of coronary artery disease was predicted not only by medical variables but also by psychological and social variables. As well as being addressed directly, these factors may help to identify patients who need to be followed more closely, so that medical complications can be reduced by treating early signs of disease progression more aggressively. PMID- 7780621 TI - Sequential changes in the distribution of type I and III collagens in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat. AB - AIM: Ventricular remodeling following acute myocardial infarction is an important factor in prognosis. The healing process, involving changes in type I and III collagens, is one of the major factors in remodelling. We therefore examined sequential changes in type I and III collagens after experimental myocardial infarction. MATERIALS AND METHODS: Hearts were excised from 1 day to 10 weeks after permanent left coronary ligation in rats. Immunohistochemical staining with a polyclonal antibody to each collagen was performed by the avidin-biotin peroxidase method. RESULTS: Type I collagen initially appeared in the peripheral zone of the infarct from 3 days after ligation, the extent of staining gradually increasing until it reached a maximal level on days 21-28, after which the distribution remained unchanged. Type III collagen appeared in the peripheral zone of the infarct from 3 days after ligation; the extent of staining reached the maximal level after 11-28 days, after which a slight decrease in the distribution was observed, although the staining did not entirely disappear. CONCLUSIONS: Type I collagen was a major factor in collagen matrix formation, especially in the relatively late phase. Type III collagen, however, contributed particularly to collagen matrix formation in the relatively early phase. This study improves current understanding of the time-dependent alterations in type I and III collagens involved in the healing process after coronary artery occlusion. PMID- 7780624 TI - Bibliography of the current world literature. PMID- 7780623 TI - Effects of delayed recanalization of an occluded acute myocardial infarction related artery using coronary angioplasty on late potentials. AB - BACKGROUND: Recent evidence suggests that late reperfusion of an occluded infarct related artery after an acute myocardial infarction may reduce the frequency of subsequent arrhythmic events. Late mechanical reperfusion by percutaneous transluminal coronary angioplasty (PTCA) under these circumstances has a high success rate. The present study was performed to test the hypothesis that the late mechanical restoration of anterograde flow in an occluded infarct artery after an acute myocardial infarction causes a resolution of late potentials. METHODS: Twenty subjects (10 men, one woman; aged 32-77 years) suffering a first acute myocardial infarction, with signal-averaged electrocardiographic (ECG) recordings and a severely occluded infarct-related artery, were prospectively identified. RESULTS: Eighteen patients underwent successful PTCA of the occluded artery 6-32 days after a first acute myocardial infarction. Late potentials were observed in 14 patients 5-22 days after the infarction. A follow-up signal averaged ECG was performed 1-8 days later. In the subgroup of 12 patients with successful reperfusion and an abnormal signal-averaged ECG before PTCA, seven (58.3%) showed resolution of the late potentials at follow-up; in these patients the filtered QRS duration showed a significant reduction (112.1 +/- 14.2 to 96.7 +/- 12.7 ms, P = 0.02), the root-mean-square voltage increased (9.8 +/- 6.5 to 33.1 +/- 15.5 microV, P = 0.017), and the duration of low-amplitude signals < 40 microV decreased after angioplasty (46.3 +/- 11.0 to 28.5 +/- 6.5 ms, P < 0.022). In contrast, two patients with late potentials before PTCA and unsuccessful reperfusion had no significant changes in signal-averaged ECG. CONCLUSIONS: In some patients with an acute myocardial infarction, late mechanical reperfusion of the culprit vessel may reduce the incidence of abnormalities on the signal averaged ECG. Whether this will improve long-term survival has yet to be confirmed in a large trial. PMID- 7780622 TI - Acute and long-term results of coronary stents and atherectomy in women and the elderly. AB - AIM: To determine the efficacy of new coronary interventions in women and the elderly. PATIENTS AND METHODS: We studied 504 patients who underwent a total of 567 procedures, comprising 275 directional coronary atherectomy and 292 Palmaz Schatz stents over a 2 1/2 year period; 18% were women and 23% were aged > or = 70 years (elderly). RESULTS: High rates of success were obtained with these procedures in women and the elderly, although the rates were lower in women than in men (89 versus 96%, P = 0.005), and similarly lower in the elderly than in younger patients (91 versus 96%, P = 0.06). In addition to the lower success rates, there was a higher incidence of procedure-related non-Q myocardial infarction and vascular complications in both the women and the elderly, independently. The degree of angiographic restenosis (> or = 50% diameter stenosis), however, was similar in women (36 versus 28% in men, P = 0.22) and in the elderly (28 versus 29% in patients ages < 70 years, P = 0.8). There were no sex-related differences in survival, late myocardial infarction, or repeat revascularization. In the elderly, although the incidence of repeat revascularization was not increased, there was a decrease in late survival (P < 0.001) and an increase in the incidence of late myocardial infarction (P = 0.02), probably reflecting the presence of other co-morbid variables. CONCLUSION: Both directional coronary atherectomy and coronary stenting can be performed safely and effectively in women and the elderly with good long-term clinical results, despite a somewhat lower rate of success and similarly higher rates of acute complications. PMID- 7780625 TI - The epidemiology of atrial fibrillation. PMID- 7780626 TI - Modulation of connexin43 expression: effects on cellular coupling. AB - INTRODUCTION: Gap junctions connect cardiac myocytes allowing propagation of action potentials. They contain intercellular channels formed by multiple different connexin proteins. The arrangement and type of gap junctions and the types, function, and interaction of connexin proteins determine intercellular resistance and can thereby influence conduction velocity and the potential for reentrant arrhythmias. Our goal was to develop genetically manipulable models to test the effects of altering expression of a major cardiac connexin (connexin43) on intercellular coupling and expression of other connexin proteins. METHODS AND RESULTS: BHK cells that are poorly coupled and BWEM cells that are well coupled were stably transfected with plasmids containing connexin43 cDNA in antisense and sense orientations. RNA blots confirmed expression of the transfected transcripts. Immunoblots showed that connexin43 protein was reduced in the BHK antisense transfectants and increased in the BHK sense transfectants compared to the parental cells. It was not detectably changed in the BWEM antisense transfectant line compared to the BWEM parental cells. Transfection of connexin43 cDNA did not affect production of connexin45 mRNA and protein nor did transfection induce expression of other previously unexpressed connexin mRNAs. Cell coupling was assessed by intercellular diffusion of microinjected Lucifer yellow in confluent cell populations. Lucifer yellow passed to a mean of 3 +/- 3 neighboring parental BHK cells, to 8 +/- 8 neighbors in the sense connexin43 transfected BHK cells, and to only 2 +/- 2 neighbors in the antisense connexin43 transfected BHK cells (P < 0.05). In contrast, dye transfer did not differ significantly between the parental BWEM cells (mean transfer = 19 +/- 14 cells) and the BWEM connexin43 antisense transfectants (mean transfer = 15 +/- 12 cells) (P = 0.20). CONCLUSIONS: These data demonstrate that stable transfection with connexin43 cDNA constructs can result in detectable changes in connexin43 expression and cellular coupling without inducing compensatory changes in the cell's connexin phenotype and, therefore, may provide a basis for future attempts at specifically modulating connexin expression and intercellular resistance in cardiac tissues. PMID- 7780627 TI - The vulnerable window for unidirectional block in cardiac tissue: characterization and dependence on membrane excitability and intercellular coupling. AB - INTRODUCTION: Unidirectional block is a requisite event in the initiation of reentry in cardiac tissue, but its initiation and behavior in the presence of tissue pathologies remain poorly understood. Previous experimental and theoretical reports on vulnerability to unidirectional block under conditions of reduced cellular coupling and reduced membrane excitability have varied due to differences in experimental and simulation protocols. METHODS AND RESULTS: We have addressed the issue of vulnerability to unidirectional block using the recent Luo-Rudy membrane model and computer simulations of propagation in a one dimensional cardiac fiber. The vulnerable window (VW) of unidirectional block from premature stimulation is expressed in units of time, VWtime, and as a range of membrane potentials at the stimulus site, VWpot. VWpot and VWtime were quantified over a range of membrane excitability and gap junction resistances (intercellular coupling). With normal membrane excitability and intercellular coupling, VWpot and VWtime were small (VWpot = 0.44 mV, VWtime = 0.39 msec). A uniform reduction (0.25x) in the degree of intercellular coupling increased VWtime and VWpot by factors of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25x) in membrane excitability (same resulting velocity) increased VWtime by only a factor of 0.4 and decreased VWpot to negligible levels. When inhomogeneities in fiber properties were introduced (intercellular coupling and membrane excitability), VWtime increased more due to inhomogeneity in membrane excitability (VWtime = 4.5 msec) than to inhomogeneity in intercellular coupling (VWtime = 1.5 msec). The simulations also clarify the dependence of the VW on the dimensions of the stimulating electrode. The length of the stimulating electrode added a factor, equal to the propagation time across the electrode length, to the intrinsic VW of the fiber. CONCLUSIONS: VWpot and VWtime are both important parameters for quantifying vulnerability to unidirectional block. In an environment with uniform distribution of fiber and membrane properties, reduced intercellular coupling has a greater effect on the VW than reduced membrane excitability. Inhomogeneous reduction of membrane excitability can significantly enhance vulnerability to unidirectional block, much more so than inhomogeneous reduction of intercellular coupling. Theoretically, stimulation at a point should be used to define the VW. Finite electrode dimensions introduce a geometrical factor that affects the measurement of the VW. PMID- 7780628 TI - Wolff-Parkinson-White syndrome presenting as the permanent form of junctional reciprocating tachycardia. AB - The substrate of the permanent form of junctional reciprocating tachycardia is an accessory pathway with no spontaneous anterograde conduction, usually located in the posteroseptal area. We report a case of this type of tachycardia with overt anterograde ventricular preexcitation. Electrophysiologic study confirmed that tachycardia was due to an accessory pathway with long retrograde conduction time; electrophysiologic findings suggested longitudinal dissociation of the accessory pathway. Radiofrequency application at the coronary sinus os resulted in disappearance of preexcitation and cure of the tachycardia. PMID- 7780629 TI - Heterogeneity in the inherited long QT syndrome. AB - Heterogeneity is present in the inherited long QT syndrome and affects the diagnosis of patients. The evidence of genetic heterogeneity is clear, with at least five genetic loci responsible for the syndrome. Phenotypic heterogeneity is less well defined, but differences in QT prolongation, T wave morphology, and the risk and frequency of syncope and sudden death are very likely. Of particular importance, it is likely that there are differences in the molecular pathophysiology of the syndrome, which are dependent on the genetic substrate present. Elucidation of the specific molecular physiology of each of the genetic subtypes of long QT syndrome will not only allow precise diagnosis and, potentially, treatment of patients with the syndrome, but will enhance our understanding of the pathophysiology of arrhythmias in general, which will extend the benefit of more precise therapy to many patients in addition to those with the long QT syndrome. PMID- 7780630 TI - Description and evaluation of the Res-Q Arrhythmia Control Device. AB - The Res-Q Arrhythmia Control Device (Intermedics Inc.) is one of the latest entries into the growing implantable cardioverter defibrillator (ICD) market. Dysrhythmias are classified according to their zone of detection, with a bradycardia zone, up to 3 tachycardia zones, and a fibrillation zone. Detection criterion, therapies, and redetection criterion within each zone are independently programmable, tailoring the setup to each individual's needs. In a hierarchical manner, this allows efficacy, urgency, and patient comfort to be appropriately balanced. Tachycardia therapy options include antitachycardia pacing (ATP), low-energy cardioversion, and high-energy shock, while VVI pacing provides bradycardia therapy. ATP programming is extremely flexible. Biphasic waveform and a maximum output of 700 V have yielded a high rate of successful implantation. Unique features include the multiprogrammable sensing autogain, which tracks evoked T waves during pacing, as well as the use of the pulse generator to perform implant testing. Major strengths include programming flexibility and individualized therapy for multiple dysrhythmias. The major shortcoming relates to a lack of stored electrograms. Although long-term follow up is not yet available, the Res-Q appears to be a capable challenger to a peer group of advanced generation ICDs. PMID- 7780631 TI - The effect of radiofrequency catheter ablation on myocardial creatine kinase activity. AB - INTRODUCTION: The primary mechanism of myocardial injury during radiofrequency (RF) catheter ablation in the heart is presumed to be thermal. Creatine kinase has been measured in serum to assess the volume of myocardial injury after ablation. However, its thermal inactivation by RF ablation could lead to underestimation of the true volume of injury. METHODS AND RESULTS: Serial RF lesions were created in 10 canine left ventricles in vivo, and serial serum creatine kinase activities were measured and compared to lesion volume. To assess the stability of myocardial creatine kinase during RF catheter ablation, 29 RF ablations were made on the epicardial surface of porcine left ventricle in vivo and a 2-mm core biopsy was rapidly removed. The cores were rapidly frozen, sectioned longitudinally in 1-mm slices, and homogenized in 0.3 M Tris buffer solution containing EDTA and dithiothreitol for subsequent analysis of creatine kinase activity. An additional 19 tissue cores from RF lesions were stained and used to determine mean lesion depth. Normal tissue biopsies were exposed to 60 seconds of hyperthermia (37 degrees to 85 degrees C, n = 190), or high-density RF current at 50 degrees C (0 to 100 mA/mm2, n = 50), and tissue creatine kinase activity was measured. There was no evidence of creatine kinase washout within the first 2 hours, and peak values were measured 5 to 7 hours postablation. Tissue creatine kinase activity in the first mm depth of RF lesions averaged 10% of control values and increased over the first 5 mm of lesion depth. The mean creatine kinase activity within the hemisphere of ablated myocardium was calculated to be 31% of control. Creatine kinase activity declined significantly at temperatures above 65 degrees C, but no difference in tissue creatine kinase activity was observed among differing levels of RF current exposure in the absence of significant heating. CONCLUSIONS: Creatine kinase activity in myocardial tissue is significantly diminished within the RF lesion. Creatine kinase activity is not stable at temperatures above 65 degrees C, which are routinely achieved within the central zone of RF ablation, and is unaffected by RF current in the absence of hyperthermia. Measurements of serum creatine kinase activity after RF catheter ablation may significantly underestimate the volume of myocardial injury. PMID- 7780632 TI - Characteristics of multiple-shock defibrillation. AB - INTRODUCTION: A new method for defibrillation allows two shocks to be combined to defibrillate with reduced current by adjusting their separation according to the cycle length of the fibrillation event. We investigated various aspects of this new method to better understand its characteristics and applicability to defibrillation. METHODS AND RESULTS: In 48 pentobarbital-anesthetized dogs, we measured the current for 50% defibrillation success using the new method with sequences of rectangular shocks. Group 1 studied the role of shock total duration and found that two-shock sequences followed a strength-duration curve similar to, but below, that for single shocks. Group 2 studied the role of amplitude and duration balance between shocks and found that two-shock sequences with equal shocks performed best. Group 3 studied whether the new method could be used with either biphasic waveforms or sequential shock pathways. Current reduction for the combined methods equaled the product of current reduction by each method, demonstrating that these methods can be effectively combined. Group 4 extended the method to include three-shock and four-shock sequences and found that a fourth shock did not further improve defibrillation. The optimum three-shock sequence required 33% lower current (P < 0.002) and 34% greater energy (P < 0.095 = NS) than a single shock. CONCLUSIONS: The new method allows defibrillation to be distributed over several fibrillatory cycles and has an improved strength duration relationship. Two- or three-shock sequences using equal shocks permit a substantial reduction of defibrillation current that can be combined with the reduction for biphasic and sequential methods. Thus, the method may have application in low-current defibrillation devices. PMID- 7780633 TI - Involvement of B1 and B2 receptors in bradykinin-induced rat paw oedema. AB - 1. The mechanisms involved in bradykinin (BK)-induced oedema in the rat paw as well as the interactions between BK and several inflammatory mediators, have been investigated. 2. Intraplantar injection of BK (1 nmol/paw) in rats pretreated with captopril (5 mg kg-1, s.c.) caused a small amount of oedema formation (0.17 +/- 0.05 ml). Des-Arg9-BK (DABK, a selective B1 receptor agonist) up to 300 nmol/paw caused minimal oedema (0.03 +/- 0.01 ml). 3. Co-administration of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), calcitonin gene-related peptide (CGRP), 5-hydroxytryptamine (5-HT), substance P (SP) or platelet activating factor (PAF) (1 pmol-1 nmol/paw) with BK (1 nmol/paw) dose-dependently potentiated BK-induced paw oedema. The rank order of potency (mean ED50, pmol/paw) for this effect was: SP (8.1) > PAF (13.7) > PGI2 (20.5) > 5-HT (23.8) > CGRP (25.7) > PGE2 (52.0). Co-administration of BK with the various inflammatory mediators resulted in maximal paw oedemas (ml) of: PGE2 (0.71 +/- 0.02); PGI2 (0.66 +/- 0.02); 5-HT (0.65 +/- 0.01); SP (0.63 +/- 0.05); CGRP (0.60 +/- 0.05) and PAF (0.47 +/- 0.02) ml. Histamine (up to 1 nmol/paw) was ineffective in potentiating the response to BK. 4. Hoe 140 or NPC 17731 (two selective B2 receptor antagonists, 0.1-3 nmol/paw) produced dose-dependent inhibition of paw oedema potentiation induced by co-injection of BK with other mediators with the following mean ID50s (nmol/paw): Hoe 140-1.4; 1.3; 1.5 and 1.1 and NPC 17731-1.0; 1.0; 0.9 and 0.7; in the presence of PGE2, PGI2, CGRP and SP, respectively. The selective B1 receptor antagonist des-Arg9 [Leu8]-BK (DALBK, up to 300 nmol/paw) had no effect.5. Daily intraplantar injections of BK (10 nmol/paw) once a day for 7 consecutive days caused a progressive and complete desensitization of the paw oedema, which was specific for BK, since paw oedema induced by PAF, PGE2, SP or histamine was not affected. In addition, the oedema caused by BK in the paw desensitized to the peptide was almost completely reversed if BK was co-injected with PGE2, PGI2 or SP (1 nmol/paw). Injection of PGE2 or SP (10 nmol/paw) together with the first BK injection (1O nmol/paw), partially prevented BK-induced desensitization.6. When animals were completely desensitized to BK, DABK (100nmol/paw) caused paw oedema(0.25 +/- 0.03 ml) which was consistently blocked by the B1 receptor antagonist, DALBK (100 nmol/paw).7. Treatment of animals with dexamethasone (0.5 mg kg-1, s.c., 24 h previously) antagonized paw oedema induced by DABK (100 nmol/paw) in desensitized paws, but not that induced by BK (3 nmol/paw) in naive paws. The steroid also prevented the recovery of oedema seen after co-injection of BK with PGE2 or PGI2 (1 nmol/paw) in desensitized paws.8. These results suggest that both B, and B2 receptors are involved in BK-induced rat paw oedema. The B2 receptors are constitutive, but induction of expression of B, receptors seems to occur only after complete desensitization of the paw to BK. In addition, very low doses of inflammatory mediators markedly potentiate BK-induced paw oedema and can attenuate BK-induced paw oedema desensitization.Such mechanisms may be relevant for the manifestation of acute and chronic inflammatory processes. PMID- 7780634 TI - Sensitization by calyculin A of brain capillary endothelial cells to endothelin 1. AB - 1. Cultured brain capillary endothelial cells of the rat respond to endothelin-1 (ET-1) by an increased activity of the Na+,K+,2Cl-, cotransporter and a mobilization of intracellular Ca2+ stores. 2. Calyculin A (1-30 nM), but not okadaic acid, sensitizes up to 100 fold the Na+,K+,2Cl- cotransporter to the action of ET-1. 3. Calyculin A (30 nM) does not modify the binding properties of ET-1 to ETA receptors. 4. Calyculin A (30 nM) inhibits ET-1 induced intracellular Ca2+ mobilization. 5. It is concluded that inhibition of protein phosphatase 1 selectively modifies the repertoire of intracellular actions of ET-1 and favours actions that are unrelated to the phospholipase C signalling cascade. PMID- 7780635 TI - The interaction of antidepressant drugs with central and peripheral (enteric) 5 HT3 and 5-HT4 receptors. AB - 1. A combined study of receptor binding in central neuronal cell membranes and functional responses in isolated segments of guinea-pig small intestine allowed characterization of the interaction of four antidepressant drugs with central and peripheral 5-HT3 and 5-HT4 receptors. 2. Clomipramine, paroxetine and fluoxetine inhibited [3H]-DAU 6215 binding to 5-HT3 recognition sites in NG 108-15 cells with IC50 values in the range 1.3-4 microM. Litoxetine had an IC50 of 0.3 microM. The specific binding of [3H]-GR 113808 to 5-HT4 recognition sites in pig striatal membranes was inhibited by all four antidepressants with negligible potency (IC50 values > or = 20 microM). 3. In whole ileal segments, concentration-response curves to 5-HT were biphasic, with the high- and low-potency phases involving 5 HT4 and 5-HT3 receptors, respectively. Curves to 2-methyl-5-hydroxytryptamine (2 methyl-5-HT: a 5-HT3 receptor agonist) and 5-methoxytryptamine (5-MeOT: a 5-HT4 receptor agonist) were monophasic. All antidepressants were used at concentrations lacking anticholinoceptor properties, as demonstrated in both electrically stimulated longitudinal muscle-myenteric plexus preparations (LMMPs) and in unstimulated LMMPs following addition of acetylcholine (100 nM). 4. Fluoxetine (0.1-1 microM) and litoxetine (0.3-3 microM) antagonized both the high and low-potency phases of the 5-HT curve. Schild analysis for the low-potency phase yielded pA2 estimates of 6.6 +/- 0.3 (Schild slope of 1.1) and of 6.6 +/- 0.1 (Schild slope of 1.1), respectively. At higher concentrations (3 microM), fluoxetine markedly inhibited the 5-HT response maximum. Clomipramine (10-300 nM) inhibited, by a mechanism independent of concentration, both phases of the 5-HT curve with a reduction of the maximum response. Paroxetine (1 microM) was ineffective on the high-potency phase, but caused a rightward shift of the low potency phase (pKB: 6.1 +/- 0.01). 5. Responses to 2-methyl-5-HT were inhibited by 1 microM fluoxetine (pKB: 5.4 +/- 0.02). Like clomipramine(30 and 100 nM), litoxetine (1 and 3 microM) produced rightward displacements of 2-methyl-5-HT induced contractions, which were virtually independent of antidepressant concentration (pKB values: 6.0 +/- 0.02 and 5.5 +/- 0.01, respectively). At higher concentrations, fluoxetine (3 microM) and clomipramine (300 nM)markedly reduced the 2-methyl-5-HT response maximum. Paroxetine (1 micro M) was ineffective.6. Responses to 5-MeOT were shifted to the right by fluoxetine (0.1-1 micro M) and litoxetine (1 and 3 microM)in a concentration-dependent manner. At higher concentrations, fluoxetine (3 microM) markedly reduced the 5-MeOT response maximum, an effect also observed with 100 and 300 nM clomipramine. Paroxetine(1 microM) was ineffective.7. In unstimulated LMMPs, the excitatory effects evoked by 5-HT, 2-methyl-5-HT and 5-MeOT and the antagonism produced by 300 nM clomipramine were comparable to those obtained in whole ileal segments. This suggests that 5-HT contained in the mucosa of whole preparations does not interfere with agonist-induced contractile responses and with the inhibitory effect of antidepressant drugs.8. In conclusion, our results show that clomipramine, fluoxetine, paroxetine and litoxetine possess low to moderate potency/affinity at both central and peripheral (enteric) 5-HT3 receptors. In contrast, all four antidepressants are virtually ineffective at central 5-HT4 receptors. Inhibition of 5-HT4 receptor mediated ileal contractions by fluoxetine, litoxetine and clomipramine may result from allostericant agonism or, more likely, from post-receptor blockade of second messenger generation. The interaction of antidepressants with central and peripheral 5-HT3 and 5-HT4 receptors may be relevant for both potential therapeutic action and adverse effects at gastrointestinal level. PMID- 7780636 TI - Pharmacological characterization of alpha 1-adrenoceptor subtypes in rat heart: a binding study. AB - 1. The alpha 1-adrenoceptor subtypes of rat heart were characterized in binding experiments performed with [3H]-prazosin as the radiolabel. The specific binding to the alpha 1-adrenoceptors was determined with 0.3 microM prazosin, because phentolamine (10 microM) was insufficient to inhibit completely the specific binding of high concentrations of [3H]-prazosin. 2. In saturation experiments, [3H]-prazosin bound to two distinct affinity sites (pKD = 10.39 and 8.19). The proportion of the low affinity sites was approximately 84% of total specific binding. Membranes pretreated with chloroethylclonidine (CEC, 10 microM) also showed two distinct affinity sites for [3H]-prazosin, although the maximum numbers of high and low affinity sites were reduced by 86 and 64%, respectively. 3. In competition experiments, [3H]-prazosin (100 pM) binding was inhibited by WB4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane) and 5 methylurapidil. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 10.43 and 8.36 for WB4101, 8.62 and 6.61 for 5-methylurapidil). However, unlabelled prazosin or HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)-ethyl)amin o) propyl)benzeneacetonitrile fumarate) competed for [3H]-prazosin binding monophasically (pKi = 10.34 and 8.28, respectively). In CEC-pretreated membranes, prazosin, WB4101, 5-methylurapidil and HV723 antagonized the [3H]-prazosin (100 pM) binding monophasically (pKi = 9.70, 9.56, 8.60 and 8.82, for each antagonist). 4. On the other hand, 1000 pM [3H]-prazosin binding was inhibited by unlabelled prazosin biphasically (pKi = 10.49 and 8.49). HV723 did not discriminate both prazosin-high and low affinity sites (pKi = 8.18). 5. These results suggest the presence of at least three distinct alpha1-adrenoceptor subtypes in rat hearts(two prazosin-high affinity sites and one prazosin-low affinity site). According to the recent alpha l-adrenoceptor subclassifications, one of the former two sites corresponds to the alpha 1B subtype with low affinities for WB4101 and 5-methylurapidil and sensitive to CEC, while another site with relatively high affinities for WB4101 and 5-methylurapidil may be classical alpha 1A, cloned alpha 1c, alpha 1D subtypes or their mixture. The prazosin-low affinity site corresponds to putative alpha 1L subtype with low affinity for HV723,which may be predominantly involved in the positive inotropic response to phenylephrine. PMID- 7780638 TI - Interaction of beta-carboline inverse agonists for the benzodiazepine site with another site on GABAA receptors. AB - 1. We examined the effects of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3 carboxylate (DMCM), a beta-carboline inverse agonist for the benzodiazepine site, on gamma-aminobutyric acid (GABA)-induced Cl-currents in several cloned rat GABAA receptor subtypes expressed in human embryonic kidney cells. The Cl- currents were measured in the whole cell configuration of patch clamp techniques. 2. DMCM at low concentrations (< 0.5 microM) occupying only the benzodiazepine site decreased GABA-induced Cl currents in the alpha 1 beta 2 gamma 2 and alpha 3 beta 2 gamma 2 subtypes as expected from an inverse agonist, but produced no change in the alpha 6 beta 2 gamma 2 subtype (perhaps a neutral antagonist). The drug at higher concentrations (> 0.5 microM) enhanced Cl- currents in all the subtypes with a half maximal concentration of 6 to 20 microM, depending on the alpha isoform. In the alpha 1 beta 2 subtype, which is without the benzodiazepine site, DMCM monophasically increased Cl- currents with a half maximal concentration of 1.9 microM. 3. Ro 15-1788 (a classical benzodiazepine antagonist) had no effect on Cl- current enhancement by DMCM and, in fact, increased the current level through blocking current inhibition by DMCM via the benzodiazepine site. Also, Cl current enhancement by pentobarbitone or by 3 alpha, 21-dihydroxy-5 alpha pregnan-20-one was additive to that by DMCM at saturating doses. It appears that the agonist site for DMCM is distinct from those for benzodiazepines, barbiturates and neurosteroids. 4. Among beta-carboline analogues, methyl-beta carboline-3-carboxylate and propyl-beta-carboline-3-carboxylate markedly enhanced GABA-induced Cl currents in the alpha 1 beta 2 gamma 2 subtype, while N-methyl beta-carboline-3-carboxamide and 1-methyl-7-methoxy-3,4-dihydro-beta-carboline did not. It appears that the 3-carboxyl ester moiety is necessary for beta carbolines to interact with a novel site on GABAA receptors as agonists. PMID- 7780637 TI - Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134,308. AB - 1. The effects induced in rats on naloxone-precipitated morphine withdrawal syndrome by the new mixed inhibitor of enkephalin catabolism able to cross the blood-brain barrier RB 101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl-L-phenylalanine benzyl ester) given alone or associated with the selective CCKB antagonist, PD-134,308, were investigated. 2. The systemic administration of RB 101 (5, 10 and 20 mg kg-1, i.v.) elicited a significant decrease in 8 of the 14 withdrawal signs evaluated. PD-134,308 (3 mg kg-1, i.p.) did not modify the expression of morphine abstinence when given alone, but induced a strong facilitation of RB 101 responses (12 of 14 withdrawal signs were decreased). This potentiation was particularly intense in peripherally mediated withdrawal signs. 3. In order to clarify the biochemical mechanisms implicated in these responses, the effects induced by the association of RB 101 and PD-134,308 on the occupation of brain opioid receptors by endogenous enkephalins were also investigated in mice. PD-134,308, as well as RB 101, inhibited [3H]-diprenorphine binding to opioid receptors. These results suggest that an increase in endogenous enkephalin levels induced by PD-134,308 could participate in the facilitation of RB 101 behavioural responses. 4. RB 101 has a promising potential role in the management of the opiate withdrawal syndrome. CCKB antagonists, such as PD 134,308 may be useful in potentiating this anti-withdrawal effect. PMID- 7780640 TI - Evidence for the involvement of different receptor subtypes in the pre- and postjunctional actions of angiotensin II at rat sympathetic neuroeffector sites. AB - 1. The effects of the nonpeptide angiotensin II receptor (AT) antagonists losartan and PD 123319 on actions of angiotensin II in the rat caudal artery and rat vas deferens preparations were investigated. 2. Angiotensin II (1.0 microM) increased perfusion pressure in isolated segments of the rat caudal artery. This increase in perfusion pressure was prevented by the AT1-antagonist, losartan (0.1 microM) but was not affected by the AT2-antagonist, PD 123319 (0.1 microM). 3. Angiotensin II (0.1-3.0 microM) produced a concentration-dependent enhancement of the stimulation-induced (S-I) efflux of [3H]-noradrenaline from isolated segments of rat caudal artery in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline. The maximum enhancement of S-I efflux was approximately 60% with 1.0 microM angiotensin II. 4. Losartan (0.01 and 0.1 microM) reduced the enhancement of S-I efflux produced by 1.0 microM angiotensin II in the caudal artery. 5. PD 123319 (0.01 microM) did not affect the enhancement of S-I efflux produced by angiotensin II (1.0 microM) in the caudal artery. However, in a higher concentration (0.1 microM), PD 123319 reduced the enhancement of S-I efflux produced by 1.0 microM angiotensin II. 6. Angiotensin II produced concentration-dependent enhancement of the purinergic twitch responses (1 pulse/60 s) in the rat vas deferens. 7. Losartan (0.03 microM) and PD 123319 (0.03 microM) each reduced the angiotensin II-induced enhancement of the twitch responses in the rat vas deferens. 8. These findings indicate that the enhancement of sympathetic neuroeffector transmission in both the caudal artery and vas deferens of the rat involves angiotensin receptor subtype(s) sensitive to both losartan and PD 123319. In contrast, the direct vasoconstrictor effect of angiotensin II in the rat caudal artery involves activation of a receptor subtype sensitive only to losartan. PMID- 7780639 TI - Functional effects of long-term activation on human beta 2- and beta 3 adrenoceptor signalling. AB - The functional effects of long-term activation of beta-adrenoceptors were investigated by measuring adenylyl cyclase activity, cyclic AMP accumulation and cyclic AMP-dependent protein kinase activity in CHW and L cells expressing either human beta 2- or beta 3-adrenoceptors. Pre-incubation of CHW and L cells expressing beta 2-adrenoceptors with 10 microM isoprenaline for 24 h produced a marked reduction in the total receptor number and dramatically reduced the capacity of the receptor to stimulate adenylyl cyclase maximally. In contrast, the ability of beta 3-adrenoceptors number was observed in L but not in CHW cells. Maximal levels of intracellular cyclic AMP concentrations were reached during the first hour of receptor activation with isoprenaline in all four cell lines. In the absence of phosphodiesterase inhibitors, cyclic AMP decreased to basal levels within 24 h of continuous stimulation. This phenomenon occurred more rapidly in cells expressing the beta 2- than the beta 3-adrenoceptors. These results confirm that, at the level of adenylyl cyclase stimulation and cyclic AMP accumulation, the beta 3-adrenoceptor is more resistant than the beta 2 adrenoceptor to long-term desensitization. However, when cyclic AMP-dependent protein kinase activity was considered, a 24 h stimulation of beta 2- and when cyclic AMP-dependent protein kinase activity was considered, a 24 h stimulation of beta 2- and beta 3-adrenoceptor expressing cells led to the desensitization of the kinase in L but not in CHW cells. In conclusion, long-term desensitization may have distinct functional effects on cell signalling depending on the receptor subtype and the cell type considered. These findings might have practical implications for future strategies involving long-term therapies with receptor agonists. PMID- 7780641 TI - Evidence for lack of modulation of mu-opioid agonist action by delta-opioid agonists in the mouse vas deferens and guinea-pig ileum. AB - 1. There is evidence from in vivo studies for an interaction of mu- and delta opioid ligands. In the present work this concept has been investigated using the mouse vas deferens and guinea-pig ileum myenteric plexus-longitudinal preparations. 2. In field stimulated vasa deferentia of the mouse, co administration of sub-effective concentrations of the delta-opioid agonist [D Pen2,D-Pen5]enkephalin (DPDPE) and [Met5]- or [Leu5]enkephalin had no effect on the dose-response curves of the mu-agonists [D-Ala2,MePhe4, Gly-ol5]enkephalin (DAMGO) and morphine. Similarly, the delta-opioid agonists did not alter the potency of morphine and DAMGO when added at different times prior to the mu opioid agonists, or when EC50 concentrations of delta-opioid ligands were co administered. Compounds with preferred activity for the putative delta 1-(DPDPE) or delta 2-([D-Ala2,Glu4]deltorphin II (Delt II)) opioid receptors were ineffective in this respect. 3. The guinea-pig ileum contains delta-opioid receptors. No function of these receptors in mediating blockage of field stimulated contractions was observed with ligands having affinity for the putative delta 1 or delta 2 subtypes nor were the agonists able to modulate responses to mu-opioid ligands in this tissue. 4. The results demonstrate the modulation of mu-opioid agonists by delta-opioid agonists does not occur in the isolated peripheral tissues examined. Thus the findings do not support the concept of a functional coupling of opioid receptors, though the results may be explained by differences between opioid systems in the brain and peripheral tissues examined. PMID- 7780642 TI - The effect of morphine on formalin-evoked behaviour and spinal release of excitatory amino acids and prostaglandin E2 using microdialysis in conscious rats. AB - 1. In the present study, the object was to examine the effects of morphine on spinal release in vivo of excitatory amino acids (EAA), prostaglandin E2 (PGE2), and a marker for nitric oxide (NO) synthesis, citrulline (Cit), evoked by a protracted noxious stimulus produced by the injection of formalin into the paw. Spinal release was monitored in conscious rats using a microdialysis probe implanted into the subarachnoid space with the active site placed at the level of the lumbar enlargement. In split dialysate samples. EAAs were measured by high performance liquid chromatography (h.p.l.c.) and PGE2 was determined by radioimmunoassay. 2. Resting concentrations in nmol ml-1 for the amino acids (mean +/- s.e.mean, n = 21) were: 4.8 +/- 0.4 for glutamate (Glu), 0.8 +/- 0.1 for aspartate (Asp), 8.8 +/- 0.8 for taurine (Tau), 24 +/- 3 for glycine (Gly), 19 +/- 3 for serine (Ser), 5.2 +/- 0.8 for asparagine (Asn), 64 +/- 4 for glutamine (Gln) and 5.2 +/- 0.4 for Cit. Mean basal release for PGE2 was 12 +/- 1 pmol ml-1. 3. Subcutaneous (s.c.) injection of 5% formalin evoked a biphasic flinching behaviour (phase 1: 0-9 min and phase 2: 10-60 min) of the injected paw. Corresponding to phase 1 behaviour, there was a significant increase (50 100%) in spinal levels of Glu, Asp, Tau, Gly, Cit and PGE2, but not Ser, Asn and Gln. A significant (P < 0.01) second phase increase in release was observed only for Cit and PGE2. However, Glu and Asp levels were increased by approximately 45%. 4. Injection of morphine sulphate (3 mg kg-1, s.c.) had no effect on resting release, but produced a significant suppression of the formalin-evoked behaviour and release of Glu, Asp, Tau, Gly, Cit and PGE2. The effect of morphine was reversed by pretreatment with 1 mg kg-1 naloxone. Naloxone by itself did not change the release or behaviour of the formalin test.5. This study demonstrates that both spinal EAA and PGE2 release patterns correlate with behavioural nociceptive responses in the formalin test and that morphine suppresses the formalin-evoked behaviours and spinal release. The reversal by naloxone of the morphine effect indicates mediation via an opioid receptor. PMID- 7780644 TI - Differential effects of OPC-18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea-pig isolated ischaemic heart. AB - 1. The effects of OPC-18790, a novel positive inotropic agent, on cardiac function and myocardial energy metabolism in the guinea-pig isolated heart with ischaemia were studied by 31P-magnetic resonance spectroscopy (MRS) and compared with those of amrinone and dobutamine. 2. Cardiac ischaemia was induced by intracoronary infusion of 15 microns microspheres to reduce coronary perfusion flow (CPF) by 50%. Microsphere embolisation caused a 40% decrease in left ventricular systolic pressure (LVSP), cardiac contractility measured by peak of ventricular pressure development (LVdP/dt) and slightly reduced heart rate. There was also a decrease in ATP and creatine phosphate (PCr) by 20%, an increase in inorganic phosphate (Pi) by 25% and an acidic shift of intracellular pH in the ischaemic heart. 3. In the ischaemic heart, OPC-18790, amrinone and dobutamine were applied at concentrations which increased LVdP/dt by about 60%. These compounds increased LVP by 15% to 30% and increased CPF by about 10%. Amrinone and dobutamine but not OPC-18790 increased heart rate. When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters. 4. Cardiac pacing at 285 beats min-1 produced decreases in LVP, LVdP/dt and CPF by about 30%, 20%, 5%, respectively and an increase in Pi, decreases in PCr and ATP, and intracellular acidosis. 5. These results suggest that degradation of high energy phosphate compounds closely relates to increase in heart rate in the ischaemic heart. Positive inotropic agents without chronotropic action seem to be beneficial in support of the ischaemic heart. PMID- 7780643 TI - Copper chelation-induced reduction of the biological activity of S-nitrosothiols. AB - 1. The effect of copper on the activity of the S-nitrosothiol compounds S nitrosocysteine (cysNO) and S-nitrosoglutathione (GSNO) was investigated, using the specific copper chelator bathocuproine sulphonate (BCS), and human washed platelets as target cells. 2. Chelation of trace copper with BCS (10 microM) in washed platelet suspensions reduced the inhibition of thrombin-induced platelet aggregation by GSNO; however, BCS had no significant effect on the anti aggregatory action of cysNO. BCS inhibited cyclic GMP generation in response to both cysNO and GSNO. 3. The effect of BCS was rapid (within 30 s), and could be abolished by increasing the platelet concentration to 500 x 10(9) l-1. 4. In BCS treated platelet suspensions, the addition of Cu2+ ions (0.37-2.37 microM) led to a restoration of both guanylate cyclase activation and platelet aggregation inhibition by GSNO. 5. The anti-aggregatory activity of GSNO was reduced in a concentration-dependent manner by the copper (I)-specific chelators BCS and neocuproine, and to a smaller extent by desferal. No effect was observed with the copper (II) specific chelator, cuprizone, the iron-specific chelator, bathophenanthroline sulphonate, or the broader-specificity copper chelator, D penicillamine. 6. In both BCS-treated and -untreated platelet suspensions, cys NO was more potent than GSNO as a stimulator of guanylate cyclase. In BCS-treated platelet suspensions there was no significant difference between the anti aggregatory potency of cysNO and GSNO; however, in untreated suspensions, GSNO was significantly more potent than cysNO. Thus, when copper was available, GSNO produced a greater inhibition of aggregation than cysNO, despite being a less potent activator of guanylate cyclase. 7. The breakdown of cysNO and GSNO was measured spectrophotometrically by decrease in absorbance at 334 nm. In Tyrode buffer, cysNO (10 microM) broke down at a rate of 3.3 microM min-1. BCS (10 microM)reduced this to 0.5 microM min-1. GSNO, however, was stable, showing no fall in absorbance over a period of 7 min even in the absence of BCS.8. We conclude that copper is required for the activity of both cysNO and GSNO, although its influence on anti-aggregatory activity is only evident with GSNO. The stimulatory effect of copper is unlikely to be explained solely by catalysis of S-nitrosothiol breakdown. The enhancement by copper of the anti-aggregatory activity of GSNO, relative to cysNO, suggests that copper may be required for biological activity of GSNO which is independent of guanylate cyclase stimulation. PMID- 7780645 TI - Effect of the NMDA-antagonist, MK 801, on benzodiazepine-opioid interactions at the spinal and supraspinal level in rats. AB - 1. Benzodiazepines potentiate morphine antinociception at the spinal level via GABAergic mechanisms. At the supraspinal level, the inhibitory effect of midazolam on morphine antinociception cannot be easily explained by GABAA receptor activation. Since excitatory amino acids play a role in central transmission, we investigated the effect of dizocilpine (MK 801) on this interaction in spinal cord and brain. 2. In rats with an intrathecal or intracerebroventricular catheter, the mechanisms of the antinociceptive effect of benzodiazepine-morphine combinations were tested during thermal nociceptive tests. 3. The principal findings of this study were that at the spinal level, midazolam potentiation of morphine antinociception can be antagonized by the NMDA antagonist, MK 801 (10 micrograms), as assessed by hot-plate and tail-flick tests. When drugs were administered supraspinally, midazolam inhibited morphine antinociception only in the hot-plate test, an effect also inhibited by MK 801. In the tail-flick assay, midazolam failed to influence the morphine response. 4. The NMDA antagonist significantly affected midazolam antinociception at the spinal level, but was not effective following i.c.v. administration of the drugs. MK 801 had no effect on morphine antinociception after i.t. and i.c.v. administration of the drugs. 5. The paradoxical effect of midazolam on morphine antinociception and its reversal by MK 801 might be due to modulation at various levels of the neuraxis and/or modulation of different pathways mediated via both GABAA and NMDA receptor mechanisms. PMID- 7780646 TI - Role of endothelin-1 and the ETA receptor in the maintenance of deoxycorticosterone acetate-salt-induced hypertension. AB - 1. To search for a possible role for endothelin-1 (ET-1) in deoxycorticosterone acetate (DOCA)-salt-induced hypertension, we examined changes in concentration of ET-1 in vascular and renal tissue in DOCA-salt hypertensive rats and evaluated the antihypertensive effect of the ETA receptor antagonist, FR139317. 2. There was an increase in aortic immunoreactive-ET (IR-ET) concentrations in association with hypertension-induced treatment. There were no significant changes in ET-1 levels in the kidney with DOCA-salt treatment. 3. In DOCA-salt hypertensive rats, a significant correlation (r = 0.83, P < 0.01) was found between aortic IR-ET concentrations and systolic blood pressure. 4. High-performance liquid chromatography analysis of the aortic extract from DOCA-salt rats revealed one major component corresponding to the elution position of synthetic ET-1. 5. The intravenous bolus injection of FR139317 (10 mg kg-1) produced a slight decrease in blood pressure in the control rats and in the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect. 6. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogenous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ETA receptors. PMID- 7780647 TI - Blockade of motion- and cisplatin-induced emesis by a 5-HT2 receptor agonist in Suncus murinus. AB - 1. The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOl), a 5 hydroxytryptamine 5-HT2A/5-HT2C receptor agonist, on motion- and cisplatin induced emesis were studied in Suncus murinus. Subcutaneous injection of DOl, 30 min prior to the emetic stimuli, dose-dependently blocked the emesis induced by motion sickness and cisplatin (20 mg kg-1, i.p.) with estimated ID50 values of 640 and 780 micrograms kg-1, respectively. 2. alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT), a peripheral 5-HT2A/5-HT2C receptor agonist, had no effect on motion- and cisplatin-induced emesis. 3. The antiemetic effects of DOl on motion- and cisplatin-induced emesis were attenuated by preadministration of ketanserin, a selective 5-HT2A receptor antagonist. 4. The present results suggest an inhibitory role for central 5-HT2 receptors in the emetic reflex mechanism and that a 5-HT2 receptor agonist may be a useful tool to investigate the involvement of 5-HT receptors in the emetic reflex. PMID- 7780648 TI - Effects of beta 2-adrenoceptor agonists on anti-IgE-induced contraction and smooth muscle reactivity in human airways. AB - 1. The beta 2-adrenoceptor agonists, salbutamol, salmeterol and RP 58802 relaxed basal tone of human isolated bronchial smooth muscle. Salmeterol- and RP 58802 induced relaxations persisted for more than 4 h when the medium was constantly renewed after treatment. 2. Salbutamol, salmeterol and RP 58802 reversed histamine-induced contractions in human airways (pD2 values: 6.15 +/- 0.21, 6.00 +/- 0.19 and 6.56 +/- 0.12, respectively). 3. Anti-IgE-induced contractions were significantly inhibited immediately after pretreatment of preparations with beta 2-adrenoceptor agonists (10 microM). However, when tissues were treated with beta 2-agonists and then washed for a period of 4 h, salmeterol was the only agonist which significantly inhibited the anti-IgE response. 4. Histamine response curves were shifted to the right immediately after pretreatment of tissues with the beta 2-adrenoceptor agonists (10 microM; 20 min), but maximal contractions were not affected. After a 4 h washing period, the histamine curves were not significantly different from controls. Concentration-effect curves to acetylcholine (ACh) or leukotriene C4 (LTC4) were not significantly modified after beta 2-agonist pretreatment. 5. These results suggest that beta 2-adrenoceptor agonists may prevent anti-IgE-induced contraction by inhibition of mediator release rather than alterations of those mechanisms involved in airway smooth muscle contraction. PMID- 7780649 TI - Pharmacology of a non-selective ETA and ETB receptor antagonist, TAK-044 and the inhibition of myocardial infarct size in rats. AB - 1. The aims of the present study were to characterize the pharmacological profile of a new endothelin (ET) receptor antagonist, TAK-044 and to consider whether it limits the extension of myocardial infarct size in rats. 2. Binding of [125I]-ET 1 to ET receptors on rabbit ventricular and cerebellar membrane fractions was inhibited by TAK-044 with IC50 values of 3.8 nM and 130 nM, respectively. 3. It inhibited ET-1, ET-2 and ET-3-induced vasoconstriction of porcine isolated coronary arteries in a competitive (ET-1, ET-2) and a non-competitive (ET-3) manner. 4. In the rat in vivo, the ET-1-induced blood pressure changes including transient hypotension followed by sustained hypertension, were inhibited by TAK 044 (0.1-10 mg kg-1, i.v.) in a dose-dependent manner. 5. Acute myocardial infarction induced by 1 h coronary occlusion followed by 24 h reperfusion in rats caused an infarct size of 60 +/- 2% (n = 12) of the area-at-risk by weight. 6. Intravenous injection of TAK-044 10 min before coronary occlusion reduced the infarct size in a dose-dependent manner: 32% and 54% reductions at 1 and 3 mg kg 1, respectively. 7. TAK-044 administered 10 min before or 1 h after reperfusion (1 mg kg-1, i.v.) showed similar inhibitory effects: 34% and 23% reductions, respectively. 8. We conclude that TAK-044 is an ETA/ETB receptor antagonist which shows strong inhibitory effects on the extension of myocardial infarct size after coronary artery occlusion-reperfusion in rats. PMID- 7780651 TI - Vascular 5-HT1-like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system. AB - 1. In anaesthetized dogs, intra-left atrial administration of 5-hydroxytryptamine (5-HT) and selected tryptamine analogues (5-carboxamidotryptamine, 5-CT; 5-methyl tryptamine, 5-MT; alpha-methyl 5-hydroxytryptamine, alpha-HT; sumatriptan, Sum) in the presence of ketanserin and MDL72222 (5-HT2 and 5-HT3 receptor antagonists, respectively), produced dose-related changes in carotid, coronary and renal vascular conductance mediated by vascular 5-HT1-like receptors. 2. In the carotid vascular bed, 5-HT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-HT = Sum > 5-MT > alpha-HT. By contrast in this vascular bed, 5-CT was a potent vasodilator. 3. In the coronary vascular bed, 5-HT, 5-CT, 5-MT and alpha-HT were vasodilators with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > 5-MT > alpha-HT. In this vascular bed, Sum was without effect. 4. In the renal vascular bed, 5-HT, 5-CT, 5 MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > Sum > 5-MT > alpha-HT. 5. The coronary (and carotid) vasodilator responses to 5-CT were antagonized by the 5-HT1-like receptor antagonists, spiperone (1 mg kg-1) and methiothepin (0.1 mg kg-1), whereas the renal vasoconstrictor responses to this tryptamine analogue were antagonized only by methiothepin. 6. It is concluded from these studies that agonist finger-printing in vivo, using tryptamine analogues,identifies and confirms the functional presence of at least two pharmacologically distinct subtypes of the 5-HT1-like receptor in the intact canine cardiovascular system. These two subtypes are located on the vascular smooth muscle and mediate direct vasoconstriction and vasodilatation responses in vivo.7. In addition, these studies confirm that the distribution of these subtypes within the major vascular beds, shows a marked heterogeneity. The carotid vascular responses to the tryptamine analogue sindicate the presence of both the vasodilator and the vasoconstrictor subtypes. The coronary vascular responses to these analogues are, however, consistent with presence of the vasodilator subtype, only. By contrast, the renal vascular responses to these analogues indicates only the presence of the vasoconstrictor subtype. PMID- 7780650 TI - The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat. AB - 1. Pregnancy is characterized by a decrease in systemic vascular resistance and a blunting of the angiotensin II (AII) pressor response. We studied the role of nitric oxide (NO) and prostanoids in these vascular changes of pregnancy in anaesthesized, ganglion blocked non-pregnant and pregnant rats. 2. Inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) led to an increase in mean arterial pressure (MAP) which was of a significantly greater magnitude in pregnant rats in late gestation than in non-pregnant rats, or rats in mid gestation. 3. The pressor response to varying doses of AII was attenuated during late pregnancy, and this attenuation was partially reversed by L-NAME. 4. The pressor response to varying doses of a vasoconstrictor, phenylephrine (PE), was also attenuated in late pregnancy. However, this attenuation was not reversed by L-NAME. 5. Inhibition of prostanoid biosynthesis with meclofenamate did not alter basal MAP, nor the pressor response to varying doses of AII or PE in pregnant and non-pregnant animals. 6. It is concluded that (a) increased NO synthesis occurs during late gestation and contributes both to the decrease in systemic vascular resistance, as well as the blunting of the pressor response to AII during pregnancy, and (b) prostaglandins are not important in the maintenance of basal vascular tone, or the blunting of the pressor response to AII during pregnancy. PMID- 7780652 TI - Canine renovascular responses to sumatriptan and 5-carboxamidotryptamine: modulation through endothelial 5-HT1-like receptors by endogenous nitric oxide. AB - 1. In anaesthetized dogs, intra-left atrial (i.l.a.) administration of the 5-HT1 like receptor agonists, sumatriptan (1-10 micrograms kg-1) and 5 carboxamidotryptamine (0.03-0.3 micrograms kg-1) produced dose-related reductions in renal blood flow and vascular conductance, which were characterized by their rapid onset and recovery. 2. In these animals, i.v. administration of the inhibitor of nitric oxide (NO) synthase, NG-nitro-L-arginine methyl ester (L NAME; 10 mg kg-1) significantly augmented the renal vasoconstrictor responses to i.l.a. sumatriptan and 5-carboxamidotryptamine. 3. The effects of L-NAME upon these responses to sumatriptan and 5-carboxamidotryptamine were significantly reversed by subsequent i.v. administration of L-arginine (1000 mg kg-1). 4. L NAME significantly attenuated the systemic hypotensive responses to i.v. acetylcholine (0.3-3 micrograms kg-1) and this effect was also reversed by L arginine. 5. L-NAME had no effect upon the renal vasoconstrictor response to i.l.a. administration of angiotensin II, nor did it affect the renal vascular conductance recovery response to brief mechanical occlusion of the renal artery. 6. These data suggest that sumatriptan and 5-carboxamidotryptamine stimulate the release of NO through the activation of a 5-HT1-like receptor located on the endothelial cells. 7. It is concluded that in canine renal vasculature, 5-HT1 like agonists (and presumably endogenous 5-hydroxytryptamine) can cause simultaneous activation of a 5-HT1-like receptor on both vascular smooth muscle and endothelial cells. The net renal vascular response to these agonists is therefore a function of both the vascular smooth muscle vasoconstriction and the concurrent vasodilator influence of NO released from the endothelium. PMID- 7780653 TI - Haemostatic mechanism in the endometrium: role of cyclo-oxygenase products and coagulation factors. AB - 1. The primary mechanism of haemostasis in the endometrium of rat was studied and results were compared to that in the mesenteric artery. 2. The bleeding time of the rat endometrium as assessed by haemoglobin output was significantly decreased after pretreatment of the animals with either indomethacin (5 mg kg-1, i.v.) or meclofenamate (3 mg kg-1, i.v.) whereas the bleeding time was significantly increased in the rat mesenteric artery. 3. The bleeding time of the rat endometrium was unchanged from control values following treatment with prostacyclin (0.5 microgram kg-1 min-1, i.v.) or 1-benzylimidazole (50 mg kg-1, i.v.) whereas the bleeding times were increased in the rat mesentric artery. 4. Administration of heparin (100 units kg-1) increased the bleeding time in the rat mesenteric artery but had no effect on the bleeding time of the endometrium. 5. Superfusion of the endometrium with 16, 16-dimethyl PGE2 (1 microgram ml-1) a vasodilator, increased the bleeding time of the endometrium but superfusion of PGE2 over the mesenteric artery did not affect the bleeding time from this site. 6. Histological studies of the mesenteric artery and the endometrium following haemostatis revealed that the haemostatic plug in the mesenteric artery was mainly composed of platelets and fibrin whereas in the endometrium it was mainly composed of fibrin. 7. These findings suggest that haemostasis in the endometrium may be mediated by the vascular tone and fibrin whereas formation of the platelet plug may be primary mechanism for haemostasis in the mesenteric artery. PMID- 7780654 TI - Angiotensin-converting enzyme (ACE) inhibitor transport in human intestinal epithelial (Caco-2) cells. AB - 1. The role of proton-linked solute transport in the absorption of the angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril maleate and lisinopril has been investigated in human intestinal epithelial (Caco-2) cell monolayers. 2. In Caco-2 cell monolayers the transepithelial apical-to-basal transport and intracellular accumulation (across the apical membrane) of the hydrolysis-resistant dipeptide, glycylsarcosine (Gly-Sar), were stimulated by acidification (pH 6.0) of the apical environment. In contrast, transport and intracellular accumulation of the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, were low (lower than the paracellular marker mannitol) and were not stimulated by apical acidification. Furthermore, [14C]-lisinopril transport showed little reduction when excess unlabelled lisinopril (20 mM) was added. 3. pH-dependent [14C]-Gly-Sar transport was inhibited by the orally-active ACE inhibitors, enalapril maleate and captopril (both at 20 mM). Lisinopril (20 mM) had a relatively small inhibitory effect on [14C]-Gly-Sar transport. pH-dependent [3H]-proline transport was not inhibited by captopril, enalapril maleate or lisinopril. 4. Experiments with BCECF[2',7',-bis(2-carboxyethyl)-5(6) carboxyfluorescein]-loaded Caco-2 cells demonstrate that dipeptide transport across the apical membrane is associated with proton flow into the cell. The dipeptide, carnosine (beta-alanyl-L-histidine) and the ACE inhibitors enalapril maleate and captopril, all lowered intracellular pH when perfused at the apical surface of Caco-2 cell monolayers. However, lisinopril was without effect. 5. The effects of enalapril maleate and captopril on [14C]-Gly-Sar transport and pHi suggest that these two ACE inhibitors share the H(+)-coupled mechanism involved in dipeptide transport. The absence of pH-dependent [14C]-lisinopril transport, the relatively small inhibitory effect on [14C]-Gly-Sar transport,and the absence of lisinopril-induced pHi changes, all suggest that lisinopril is a poor substrate for thedi/tripeptide carrier in Caco-2 cells. These observations are consistent with the greater oral availability and time-dependent absorption profile of enalapril maleate and captopril, compared to lisinopril. PMID- 7780655 TI - Suppression by the sumatriptan analogue, CP-122,288 of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin. AB - 1. The effects of an intravenously administered sumatriptan analogue were examined on c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, evoked within trigeminal nucleus caudalis (TNC) and other brain stem regions 2 h after intracisternal injection of the irritant, capsaicin (0.1 ml, 0.1 mM), in pentobarbitone-anaesthetized Hartley guinea-pigs. 2. C-fos-LI was assessed in eighteen serial sections (50 microns) using a polyclonal antiserum. A weighted average, reflecting total expression within lamina I, IIo of TNC was obtained from three representative levels (i.e., at -0.225 mm, -2.475 mm and 6.975 mm.). 3. Capsaicin caused significant labelling within lamina I, IIo, a region containing axonal terminations of small unmyelinated C-fibres, as well as within the nucleus of the solitary tract, area postrema and medial reticular nucleus. A similar distribution of positive cells was reported previously after intracisternal injection of other chemical irritants such as autologous blood or carrageenin. 4. Pretreatment with a conformationally restricted sumatriptan analogue (with some selectivity for 5-HT1B and 5-HTID receptor subtypes) CP 122,288, reduced the weighted average by approximately 50-60% (P < 0.05) in lamina I, IIo at > or = 100 pmol kg-1, i.v., but did not decrease cell number within area postrema, nucleus of the solitary tract or medial reticular nucleus. A similar pattern was reported previously following sumatriptan, dihydroergotamine or CP-93,129 administration after noxious meningeal stimulation. 5. We conclude that modifications at the amino-ethyl side chain of sumatriptan dramatically enhance the suppression of c-fos expression within TNC, a finding consistent with its remarkable potency against neurogenic plasma protein extravasation within dura mater. CP-122,288 and related analogues may serve as an important prototype for drug development in migraine and related headaches. PMID- 7780656 TI - 5-Hydroxytryptamine (5-HT)4 receptors in post mortem human brain tissue: distribution, pharmacology and effects of neurodegenerative diseases. AB - 1. The distribution, pharmacology and effects of neurodegenerative diseases on 5 HT4 receptors in human brain have been characterized in vitro. 2. The 5-HT4 receptor in post mortem human brain tissue was specifically labelled with [3H]-GR 113808. In human putamen, this ligand labelled a homogeneous population of sites, with an apparent affinity (-log Kd) of 10.1 and a density (Bmax) of 5.73 fmol mg 1 tissue. The pharmacology of this site was characterized by use of a series of displacing ligands, and the following rank order of apparent affinities (with mean +/- s.d. -log Ki values in parentheses) was generated: GR113808 (10.05 +/- 0.04) > SDZ 205,557 (8.65 +/- 0.08) > DAU 6285 (7.95 +/- 0.04) > BIMU-1 (7.81 +/- 0.06) > DAU 6215 (7.42 +/- 0.23) > tropisetron (7.39 +/- 0.23) > 5-HT (7.32 +/- 1.00) > BIMU-8 (7.25 +/- 0.04) > (R)-zacopride (5.82 +/- 0.04). The Hill coefficients were not significantly different from unity, consistent with an interaction at a single site. A comparison of the affinities of these compounds with those obtained from guinea-pig striatum indicated no evidence of species differences. 3. The regional distribution of 5-HT4 receptors was assessed by determining the density of binding sites for [3H]-GR 113808. The distribution were as follows (with mean +/- s.d. Bmax values, fmol mg-1 tissue, in parentheses): caudate nucleus (8.7 +/- 1.5), lateral pallidum (8.6 +/- 5.5), putamen (5.7 +/- 3.0), medial pallidum (3.8 +/- 0.9), temporal cortex (2.6 +/- 0.6), hippocampus (2.4 +/- 0.8), amygdala (2.3 +/-1.1), frontal cortex (1.7 +/- 0.5), cerebellar cortex (<1.0). In these studies, the affinities of GR 113808 were not significantly different.4. The density of 5-HT4 receptors selected from regions of post mortem brains of patients with Parkinson's disease, Huntington's disease and Alzheimer's disease were compared to age-matched controls. In Parkinson's disease, there was no significant difference between control or patient values(mean +/- s.d. Bmax values, fmol mg-1 tissue; putamen, control 4.74 +/- 0.07, patient 5.86 +/- 1.48; substantia nigra, control 4.21 +/- 2.56, patient 5.57 +/- 0.10). In Huntington's disease, there was a significant decrease in putamen (control 5.33 +/- 1.08, patient 2.68 +/- 1.08), while in Alzheimer's disease, there was a marked loss of receptors in hippocampus (control 2.34 +/- 0.62, patient 0.78 +/- 0.61), in frontal cortex (control,1.76 +/- 0.19, patient 1.30 +/- 0.22). Receptor density in temporal cortex showed a decrease, but did not achieve statistical significance (control 2.06 +/- 0.21, patient 1.44 +/- 0.64).5. These data suggest a heterogeneous distribution of 5-HT4 receptors in human brain, with high to moderate densities in basal ganglia and limbic structures. These receptors may not be principally co-localized on dopaminergic cell bodies or terminals, given the lack of change observed in Parkinson's disease. The loss of 5-HT4 receptors in the putamen in Huntington's disease raises the possibility of their presence on intrinsic striatal GABAergic or cholinergic neurones. The marked loss of receptors in hippocampal and cortical regions in the brains from patients with Alzheimer's disease is consistent with a role for the 5-HT4 receptor in cognitive processing. PMID- 7780657 TI - Further investigations into adenosine A1 receptor-mediated contraction in rat colonic muscularis mucosae and its augmentation by certain alkylxanthine antagonists. AB - 1. The alkylxanthine antagonists, 8-phenyltheophylline (8-PT), 8-p sulphophenyltheophylline (8-SPT) and 1,3,7-trimethylxanthine (caffeine) produced rightward displacements of contractile concentration-effect curves to 5'-N ethylcarboxamidoadenosine (NECA) in rat isolated colonic muscularis mucosae (RCMM) with concentration-ratios consistent with adenosine receptor blockade. The non-xanthine antagonist, 9 fluro-2-(2-furyl)-5,6-dihydro [1,2,4] triazo to [1,5 c]-quinazin-imine (CGS15943A) also antagonized contractions to NECA with an affinity (pKB8.1-8.5) consistent with adenosine A1 receptor blockade. 2. In addition to producing rightward shifts of the concentration-response curves, the maximum contractions to 5'-N-ethylcarboxamidoadenosine (NECA) were also markedly increased in the presence of 8-PT (by 83 +/- 16% at 1 microM), 8-SPT (by 37 +/- 7% at 10 microM) and caffeine (by 45 +/- 5% at 100 microM) but were unaffected by CGS15943A (at 0.01 and 0.03 microM). 3. As with NECA, the maximum contractions to the adenosine A1 receptor agonists R-phenylisopropyladenosine (R-PIA) and N-[(1S, trans)-2-hydroxyclopentyl] adenosine (GR79236) were both antagonized and augmented by 8-PT. In addition, the contractions to NECA in the presence of 8-PT (1 microM) were inhibited by nanomolar concentrations of 8-cyclopentyl-1,3 dipropylxanthine (DPCPX). 4. The non-selective phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (1 microM) produced a marked increase in the NECA maximum without producing a rightward shift in the NECA curve, whereas a higher concentration (10 microM) virtually abolished responses. The PDE type III inhibitor,milrinone (1 microM), the type IV inhibitor, rolipram (10 microM), and the type V PDE inhibitor, zaprinast(3 microM), were all without effect on NECA responses in RCMM.5. Partial inhibitions of contractions to NECA were produced by indomethacin (at 3 or 10 micro M) or piroxicam (at 3 microM). Responses to GR79236 were also partially inhibited by indomethacin. In the presence of indomethacin, 8-PT was still able to enhance markedly the maximum contractions obtained to NECA in RCMM.6. The present study has shown that certain alkylxanthine antagonists (but not the non-xanthineCGS15943A) produced a marked augmentation of adenosine Al receptor-mediated contractions inRCMM. The mechanism of this augmentation is, as yet, not known but is unlikely to result from inhibition of PDE. This study has also shown that adenosine Al receptor-induced contractions inRCMM are mediated, in part, via products of the cyclo-oxygenase pathway. PMID- 7780658 TI - Karyotype evolution in holocentric chromosomes of three related species of triatomines (Hemiptera-Reduviidae). AB - C-banded karyotypes, DNA content and the male meiiotic process of Triatoma platensis and Triatoma delpontei are compared with those of Triatoma infestans, the main vector of Chagas disease in South America. These three species present the same diploid chromosome number 2n = 22 (20 autosomes + XX male/XY female). They also have several cytogenetic traits that differ from all other triatomines: large autosomes, C-heterochromatic blocks and meiotic heteropycnotic chromocenters formed by autosomes and sex chromosomes. In spite of these similarities, each species presents different chromosomal behavior during male meiosis, distinct DNA content and a specific amount and localization of the C heterochromatin. The differences in DNA content are mainly due to the variation in C-heterochromatin amount, which may be interpreted as loss and/or gain of C regions. This interpretation is supported by the presence of meiotic and mitotic chromocenters that facilitate the transference of C-positive material. The cytogenetic data presented in this work suggest that T. infestans and T. platensis are more closely related to each other than to T. delpontei. It can also be inferred that the differences in distribution and amount of heterochromatin do not play a direct role in speciation in this group. PMID- 7780659 TI - Do chiasmata disappear? An examination of whether closely spaced chiasmata are liable to reduction or loss. AB - The questions of whether closely spaced crossovers could be misidentified as single chiasmata or could cancel out each other and whether exchange could occur without chiasma formation were examined in Locusta migratoria. Monochiasmate bivalents that showed differential sister chromatid staining following bromodeoxyuridine incorporation were screened for their patterns of label distribution. Half of the chiasmata were associated with an exchange between dark and lightly stained chromatids, as expected if recombination involved any two non sister chromatids chosen at random. Two variant types of label distribution were also seen: approximately 10% of all monochiasmate bivalents had an anomalous distribution of dark and light chromatids around the chiasma, and in three of the 1365 bivalents screened a second type of anomalous pattern was observed for the first time, in which all four chromatids had a label exchange at the chiasma. The observed incidence of the latter was considerably less than expected if they originated through a four-strand double crossover with closely positioned exchanges. Analysis of label distribution patterns in monochiasmate bivalents did not produce evidence of the other configurations expected if two closely spaced exchanges could be misidentified as single chiasmata or could cancel one another out so as not to form a chiasma. We conclude that analysis of chiasma frequencies and distributions offers an accurate means of assessing recombination in organisms with favourable cytology. PMID- 7780660 TI - The developmental stage of inactivation of rye origin rRNA genes in the embryo and endosperm of wheat x rye F1 hybrids. AB - To identify the developmental stage during which the preferential inactivation of rRNA genes from the rye parent occurs in wheat x rye hybrids, nucleolar activity was evaluated in the embryo and endosperm of developing seeds of the hybrids. The hybrids were obtained from crosses of euploid and aneuploid lines of hexaploid wheat, Triticum aestivum cv. Chinese Spring, with rye, Secale cereale cv. Centeio do Alto. The number of nucleolar organizing regions (NORs) and nucleoli present in the embryo and endosperm cells of wheat, and wheat x rye F1 hybrids, at different times after fertilization was scored by silver staining. The inactivation of rDNA of rye origin in F1 hybrids occurs simultaneously in the embryo and in the endosperm between 4 and 5 days after fertilization, when these have been through six and 10 cell cycles respectively. We conclude that the genomic interactions leading to the inactivation of the rye origin rDNA is a time dependent process, related to the developmental stage and independent of the number of cell cycles (DNA replication rounds) they have been through. PMID- 7780661 TI - Identification of highly conserved loci by genome painting. AB - Fluorescence in situ hybridization was used to identify patterns of DNA similarity among the genomes of several rodent taxa. Total genomic or Cot-1 DNAs were used as hybridization probes against metaphase preparations across different taxonomic levels, including three species of Microtus (suborder Sciurognathi), three species of Microtus (suborder Sciurognathi), Mus musculus (suborder Sciurognathi) and Ctenomys steinbachi (suborder Hystricognathi). The hybridization patterns of Mus or Peromyscus (sciurognath) DNA to Mus metaphases, which were consistent with what is known of the satellite sequences in these species, demonstrated the efficacy of this approach for molecular cytogenetics and evolutionary biology. Additional hybridizations to chromosomes of Ctenomys or Microtus identified loci consisting of highly conserved DNA sequences. This approach has proved useful in investigating genome homologies across divergent rodent lineages. Chromosome microdissection can be used to characterize these regions further. PMID- 7780662 TI - Synaptonemal complex analysis in spermatocytes and oocytes of rainbow trout, Oncorhynchus mykiss (Pisces, Salmonidae): the process of autosome and sex chromosome synapsis. AB - The surface-spreading synaptonemal complex (SC) technique was employed to analyze spermatocytes and oocytes of rainbow trout in order to visualize the process of autosome and sex chromosome synapsis in this species. The structure of lateral elements (LEs) of the SC and the chromosome synapsis process at the stages of leptotene, zygotene and pachytene are described. Comparative analysis of SCs of spermatocytes and oocytes showed a difference in the synaptic process, i.e. in spermatocytes all LEs were synapsed before the appearance of centromeric regions in the biarmed elements, while in the oocytes some fully synapsed LEs, including the centromeric region of the biarmed elements, were found together with fully or partially unsynapsed LEs. In males the sex chromosome synapsis starts only after all autosomes have synapsed. Irregular synapses involving three or four LEs were found in 3.4% of the cells analyzed in mid or late zygotene. Multivalents were found in males and females. Some aspects of initial meiotic development and their implications in rainbow trout cytogenetics, genetics and evolution are discussed. PMID- 7780663 TI - General characteristics of the polytene chromosome from ovarian pseudonurse cells of the Drosophila melanogaster otu11 and fs(2)B mutants. AB - Polytene chromosomes of good cytological quality from pseudonurse cells (PNCs) of fs(2)B and otu11 mutants were obtained, photomaps for otu11 mutants were constructed and the general characteristics of polytene chromosomes from salivary glands (SGs) and PNCs were compared. Three conditions were found to improve the cytological quality of PNC chromosomes: temperature below 18 degrees C, a protein rich medium and presence of the Y-chromosome. Detailed comparison of the chromosome banding pattern from SGs and PNCs has shown only minor differences between them. The frequency of asynapsis appeared to be 10 times higher for PNC chromosomes. Despite previous reports, features such as breaks and ectopic contacts turned out to be also typical for PNC chromosomes, but with remarkably lower frequencies. PMID- 7780666 TI - [Bibliography. Writing rules for references]. AB - Scientific authors and editors have some years ago established some international rules concerning the presentation of the references. This paper describes the principles of these rules and gives explanations for their use, particularly in the most common types of publication: journal articles, books, book chapters, theses, and abstracts in conference proceedings. PMID- 7780665 TI - [Evaluation of a training program for nurses specializing in anesthesia and resuscitation in Cambodia]. AB - Following the signing of a treaty drafted between the Cambodian Ministry of Health, Medecins Sans Frontieres, and the universities of Paris Nord and Bordeaux II, the first class of sixteen nurses completed the training in anesthesia and resuscitation, between September 1991 and June 1993. The training course took into account the special context in which the course was planned and organized. By bringing together the specific skills of non-government organizations and universities, the students obtained high quality professional skills which have become extremely rare in Cambodia, where almost all competent health-care professionals have disappeared. The results of the program were evaluated several months after the graduation. Using quantitative and qualitative methods, evaluators tried to assess if the nurses were able to apply what they had learned, if the course material was relevant, and how well the nurses adapted in terms of actual work, and professional recognition and development. Eight months after graduation, the nurse anesthetists' activities represented approximately 24% of the total activity of the departments in which they worked. Thirteen of the sixteen nurses received significant professional recognition for their responsibilities in the departments, and for their independence in administering anesthesia. The working conditions were satisfactory, and the nurses were able to correctly apply what they had learned and solve many problems. However, because the anesthesia and resuscitation departments were being set up at the time of their arrival, the nurses were not able to fully care for the patients during the pre- and post-operation periods. Objectives for improving the training courses were defined, following a detailed analysis of the results of the study. However, proper supervision of the newly trained nurses remains an essential element in maintaining their competencies and motivation. By 1997, fifty-four people (fourty five nurses and nine doctors) should be trained in anesthesia and resuscitation. The continuation of the school depends on the possibility of the Cambodians to take charge of the program. For this purpose, two of the graduate nurses began training as teachers in November 1993. PMID- 7780664 TI - Yeast artificial chromosome cloning of the beta-catenin locus on human chromosome 3p21-22. AB - beta-Catenin has emerged as an important component of the adherens junctions between epithelial cells. As a result of studies of its interaction with the APC gene product, it has been implicated in the development of colorectal cancer. alpha-Catenin, beta-catenin, E-cadherin and APC appear to mediate contact inhibition in epithelia. As part of the study of the organization of the beta catenin gene, we have isolated yeast artificial chromosomes (YACs) to characterize its intron/exon structure. YAC fluorescence in situ hybridization analysis and polymerase chain reaction analysis of somatic cell hybrid DNAs show that beta-catenin maps in the 3p21-22 region, the location of tumour-suppressor genes deleted in small-cell lung cancer (SCLC) and other disorders. beta-Catenin YACs will provide a source of microsatellite markers useful in loss of heterozygosity studies to assess the importance of beta-catenin deletions in SCLC. PMID- 7780667 TI - ["Silence, people are dying..." The Damergou famine, an examination of the facts]. AB - This study illustrates the importance of rapid and rigorous nutritional surveys to evaluate precarious nutritional situations in the context of media uproar. It was performed in July 1993 in the Damergou district of Tanout in the Zinder department of Niger. In October 1992, the early warning system (SAP for Service d'alerte precoce) in the department reported and evaluated the food production deficit in the district. A food aid strategy was implemented according to these findings, and food was distributed from May. During June, 1993, a non governmental organisation (NGO) used a tabloid press report to dramatise the situation, and declare that 75% of the children were malnourished, and that there were 56,000 people starving and unable to move to look for food. An international aid spiral of bidding and outbidding followed, based on simple presumption, probably justified, but not verified. The first surveys sent from the headquarters were unable to make any reliable evaluations or pertinent recommendations. The departmental health office then performed a rapid anthropometric nutritional survey (RANS) using a representative sample of the population. The survey was a cluster survey involving 29 villages and including 1,088 children between the ages of 6 months and 6 years old and their mothers. The 29 villages account for 10% of the population of the district. The findings were as follows: 2.8% of the families had emigrated since the harvest. The average price of a tiya (approximately 2.5 kg) of millet was 183 FCFA (French African Francs), the normal price at this time of year. The reserve of animal stock was 8.6 heads per family, inconsistent with massive destocking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780669 TI - [The difficult dialogue between researchers and health development planners. Whose domain is health?]. PMID- 7780668 TI - [Street children and AIDS in Haiti]. AB - This study is a qualitative inquiry KAP about sexuality, and adoption and preservation of safe sexual behaviors, among the children of the street in Port au-Prince, Haiti. Three groups of participating children of the street were observed in Port-au-Prince for three months, during June through August 1991. The information was collected with the use of pre-tested charts for each theme chosen. Then, individual interviews were conducted with leaders identified among the educators and children of the street. One of the main goals of Aids educational programs of street children should be to make them believe in the existence of the disease, and the real risk it poses for death. The strategies that we will use to convince them should deal with the different social, psychological, economical, and environmental factors that characterized the children as follows: 1) their adherence to a peer group and the relationship of power between the older and younger children; 2) the fundamental importance of money in their life, and that all relationships that they have are based on the capacity of people to give them something, such as money; 3) the role of their social appearance and their need to behave like other children for even one day; 4) their low self-esteem; 5) their feeling of powerlessness and resignation related to their living conditions; 6) the influence of the street culture; and 7) their understanding of sexuality as an immediate pleasure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780670 TI - [Vitamin A deficiency and food consumption of children aged 6 to 84 months in a Mali rural area]. AB - A cross-sectional study was carried out during the dry season, within the framework of an extension of an existing sanitary program. In December 1991, a cluster sample of 2,631 children was selected in a rural district of Mali, in the district of Koutiala, with good agricultural conditions. A sub-sample of 262 mothers was selected for interviews concerning their knowledge and attitudes about vitamin A deficiency symptoms. Prevalence of clinical symptoms was 2% for night blindness, 0.3% for Bitot's spots and 0.2% for corneal scars. Night blindness was more common after 3 years. The study of weekly consumption of vitamin A rich foods, made on a sample of 519 children, revealed that only 3.3% ate vitamin A rich foods less than seven times a week and 2.7% never ate any. According to the recommended dietary allowances, vitamin A deficiency was not a public health problem in this region. However, these results do not agree with those of the clinical study. It should be noted also that protein energy malnutrition is scarce among the children. These results allowed an estimate of the prevalence of vitamin A deficiency, but were insufficient for the design of strategies to reduce this prevalence. Simple and relatively cheap epidemiological methods like case-control studies are not commonly used in developing countries. These methods could be used to obtain a better estimate of social, cultural and biological risk factors, and therefore, better targeting interventions. PMID- 7780671 TI - [Effectiveness of coils and mats for protection against malaria vectors in Cameroon]. AB - The evaluation of the effectiveness of coils and mats on mosquitoes, especially malaria vectors was carried out in the Southern Cameroon. The study was performed in the Nsimalen village from November 1993 to August 1994. Two brands of coils: Timor and Moon Tiger containing 0.15% W/W of esbiothrin and two brands of mats: ARS MATS (containing d-allethrin) and Moon Tiger (with S biothrin and diethyl toluamide) were tested. The evaluation was based on night catches on human bait inside houses. A catcher was sitting at two meters of a coil or a mat. Mosquitoes were caught during five consecutive nights per month in five houses. Two of the five houses were protected with the coils, two others with the mats and the fifth was used as control. Each night, coils and mats were rotated in such a way that at the end of the five nights, each house has been protected twice with coils, twice with mats and had served once as control. The composition of the mosquito samples collected was analysed and the reduction rate of bites was calculated for each method. A thousand and twenty nine mosquitoes were caught in all. Two hundred and fifty nine mosquitoes in houses with coils, 180 in those with mats and 590 in the houses which served as control. Anopheles moucheti and Mansonia s.p. accounted more than 90% of the samples; Anopheles gambiae s.s. represented 4 to 9%. Coils reduced malaria vectors bites by 82.8% and mats by 90.5%. Mansonia bites were reduced by 66% only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780672 TI - [The recycling of waste water and mosquitoes]. AB - Recycling waste water in the Acheres complex (North-West Paris) is based on both sophisticated industrial techniques and simple agricultural methods. The sewage farms and settling pools provide suitable breeding sites for more than ten mosquito species. Aedes caspius is the major pest for the local population. Moreover Culex pipiens (anthropophilic form) breeds in the sewers of the neighbouring towns. Mosquito control is based early ground treatment of breeding sites. Temephos and fenotrothion are used against A. caspius. Spherimos (Bacillus sphaericus) is used to control C. pipiens. The two insecticides have no adverse effect on humans or the environment and Spherimos is harmless. Aedes pest have been virtually eliminated. Urban Culex control is generally good despite being performed by less well trained municipal employees. In the areas treated by the specialized team of the SIAAP, pest mosquitoes have disappeared. The techniques used in the Acheres complex do not require sophisticated equipment. Thus, if adapted to local ecological, epidemiological and financial conditions they could be transferred to developing countries. PMID- 7780673 TI - [Lipid profile during specific malaria therapy in Gabonese children]. AB - We report specific dyslipidemia in Gabonese children aged 18 months to 4 years old treated with Halfan for malaria. This is observed in addition to the hypoglycemia typically associated with malaria. C-HDL (high density lipoprotein) fell on day 0 (D0), then increased during the treatment. Triglycerides (TG), total cholesterol (TC) and non-esterified fatty acids (NEFA) rose on D0. CT continued to rise evenly throughout the treatment, whereas TG declined. The differences with respect to normal values are significantly different as assessed by the Student test. We report metabolic variation and tolerance to Halfan. PMID- 7780674 TI - Efficacy and gastroduodenal safety of a fixed combination of diclofenac and misoprostol in the treatment of arthritis. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective therapy for the management of arthritis, but their use is restricted by the risk of gastrointestinal complications from NSAID-induced ulceration. The elderly, in particular, are vulnerable to such damage and complications. Misoprostol is the only cytoprotective drug found to be effective in the prevention of both gastric and duodenal ulcers associated with NSAIDs. A fixed-combination of diclofenac 50 mg/misoprostol 200 micrograms has been evaluated for efficacy and safety in the treatment of arthritis. Pharmacokinetic studies of the fixed combination have found that no drug-drug interaction occurs between misoprostol and diclofenac after either single or multiple doses, and the bioavailability of misoprostol and diclofenac are comparable with that of misoprostol and diclofenac given alone. This fixed combination was found to be equivalent to other NSAIDs in the control of symptoms and other parameters of arthritis. The fixed combination was generally well tolerated, although the occurrence of abdominal pain and diarrhoea was slightly more frequent than with other NSAIDs. This contrasts with a 2- to 3 fold reduction in the rate of gastroduodenal damage with the fixed combination compared with the rate associated with other NSAIDs. These results indicate that the diclofenac 50 mg/misoprostol 200 micrograms combination should be considered in preference to other NSAIDs when treating patients at risk of ulcer complications. PMID- 7780675 TI - The iatrogenic cost of non-steroidal anti-inflammatory drug therapy. AB - The secondary gastrointestinal effects associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) are well documented in the medical literature. Less addressed is the 'iatrogenic' cost due to the treatment of these secondary effects. Epidemiologic and clinical studies report that the cost of NSAIDs is multiplied by a coefficient that ranges from 1.45 to 3, if the cost of treating the induced gastrointestinal complications is considered. A simple methodology incorporating the direct medical cost of treating complications has been developed to calculate a 'shadow price' of an NSAID, thus reflecting the real cost to the payer of NSAID therapy. The model has been used to compare three NSAIDs on the basis of their relative prices and gastroduodenal toxicity. PMID- 7780676 TI - Historical overview of non-steroidal anti-inflammatory drugs. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are efficacious in the control of arthritis symptoms and have become the mainstay of arthritis therapy. While NSAIDs' chief mechanism of action has long been assumed to be the inhibition of prostaglandin synthesis, further investigation has implicated additional mechanisms, and shed light upon additional side-effects. Adverse renal effects and effects on bone and cartilage metabolism are counted among worrisome NSAID induced side-effects, but gastrointestinal side-effects represent the greatest threat to chronic NSAID users. It is important that we combine documented experience of side-effect risk with our growing knowledge of potential risk to frame a prescriptive approach to the arthritis patient that encompasses symptom management as well as patient protection. PMID- 7780677 TI - Non-steroidal anti-inflammatory drugs and renal function. AB - The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a range of renal effects, including interference with fluid and electrolyte homoeostasis. Common adverse effects are generally mild and transient; less common but more severe effects include reversible renal insufficiency, interstitial nephritis and papillary necrosis. Any of these effects can influence the clinical course of patients at risk because of illness, debility or age. Acute renal failure associated with NSAID use has been reported to account for up to 15.6% of cases of drug-induced renal failure. NSAID-induced haemodynamic renal failure is virtually always reversible with appropriate management; the relatively rare complications of interstitial nephritis and papillary necrosis are more often irreversible. NSAID-related impairment of kidney function is probably due in large part to inhibition of prostaglandin synthesis. Use of a prostaglandin E1 (PGE1) analogue has been suggested to prevent some of the adverse renal effects of NSAIDs in patients at high risk, an interesting possibility that deserves further evaluation. PMID- 7780678 TI - Quantitative cartilage imaging. PMID- 7780679 TI - Epidemiology and prevention of non-steroidal anti-inflammatory drug effects in the gastrointestinal tract. AB - Lesions of the gastric, duodenal and intestinal mucosae are found in large numbers of patients using non-steroidal anti-inflammatory drugs (NSAIDs); however, no markers have yet been isolated to identify patients at risk for developing gastrointestinal problems or to predict which patients with lesions are at risk for developing catastrophic complications. There appears to be a poor correlation between the presence of ulcer disease and the appearance of symptoms while patients are using NSAIDs. The ideal treatment--namely, withdrawal from NSAIDs--may not always be practicable in patients who require the analgesic benefit of these otherwise generally innocuous agents. It is incumbent on the clinician to identify the agent most appropriate for the needs of the individual, and to supplement NSAID therapy, where appropriate, with a means of preventing or minimizing adverse effects. Four classes of drugs are used to prevent NSAID related gastric mucosal damage: histamine (H2)-receptor antagonists (ranitidine, cimetidine, nizatidine, famotidine); gastric acid-pump inhibitor (omeprazole); barrier agent (sucralfate); and prostaglandin analogue (misoprostol). The current therapies (H2 antagonists and barriers) have not lived up to their promise for preventing gastroduodenal erosion. Moreover, such protection as they provide is limited to the duodenal mucosa; they afford no protection to the gastric mucosa. Preliminary data indicate that an acid pump inhibitor may be useful, but large scale studies have yet to be reported. Acute and long-term studies of the prostaglandin analogue misoprostol have shown that this agent has an important role as an adjunctive therapy to prevent both gastric and duodenal ulceration due to NSAIDs. PMID- 7780680 TI - Involvement of thiol groups in the impairment of cardiac sarcoplasmic reticular phospholipase D activity by oxidants. AB - Considerable phospholipase D (PLD) activity is localized in myocardial sarcoplasmic reticular (SR) membranes, where it may take part in the regulation of Ca2+ movements. In this study, we examined thiol group dependence as a possible regulatory mechanism for SR PLD. SR membranes isolated from rat heart were exposed to four types of thiol group modifiers, which all induced a decrease in SR PLD activity that was prevented by dithiothreitol. Furthermore, since abnormalities in thiol status and Ca2+ homeostasis are characteristic for the myocardial cell damage induced by oxidative stress, we also studied the effects of oxidants on the SR PLD activity. The enzyme was not affected by xanthine xanthine oxidase, but was depressed by hydrogen peroxide and by hypochlorous acid. These inhibitory effects were prevented by catalase as well as by methionine and dithiothreitol, respectively. Furthermore, reduced glutathione protected against the hydrogen peroxide-induced depression, whereas oxidized glutathione inhibited SR PLD. The results indicate that SR PLD activity is inhibited by nonradical oxidants, hydrogen peroxide and hypochlorous acid, through reversible modification of associated thiol groups. Thus, the enzyme may be controlled by the glutathione redox status of the cardiac cell. PMID- 7780681 TI - Modulation of the endogenous leukotriene production by fish oil and vitamin E. AB - We investigated the effects of fish oil and vitamin E on the endogenous leukotriene production. 10 healthy volunteers were supplemented for 1 week with fish oil (containing 40 mg/kg body weight per day of eicosapentaenoic and docosahexaenoic acid), vitamin E (540 mg, i.e., 800 IU of D-alpha-tocopherol per day), or with both agents. Treatment resulted in a significant increase in the eicosapentaenoate concentration in red blood cell membranes and/or in the vitamin E concentration in serum. In addition, nine obese patients were investigated who were on a hypocaloric diet including 10 mg vitamin E/day for 8 weeks. This diet was associated with a significant decrease in serum vitamin E concentration. The urinary concentration of leukotriene E4 plus N-acetylleukotriene E4 served as a measure for the endogenous leukotriene production. Fish oil reduced leukotriene production in eight of the 10 healthy individuals. After vitamin E supplementation, urinary leukotrienes were significantly reduced in all of the healthy volunteers. The combination of vitamin E plus fish oil had no synergistic effect on leukotriene production in the individuals tested. The decrease in serum vitamin E concentration during the hypocaloric, 10 mg vitamin E/day diet was associated with an increase in urinary leukotrienes in 8 of the 9 obese patients. Urinary prostaglandin metabolites, determined as tetranorprostanedioic acid, increased or decreased in parallel with urinary leukotrienes in most individuals; however, changes were less pronounced than those observed with leukotrienes. We conclude that the endogenous leukotriene production can be reduced effectively by high doses of fish oil or vitamin E, whereas vitamin E depletion is associated with an increase in leukotriene generation. PMID- 7780682 TI - Lyso-PAF:acetyl-CoA acetyltransferase and CDP-choline cholinephosphotransferase activities in the rabbit endometrium. AB - Endometrial platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3 phosphorylcholine) levels change significantly during the pre-implantation period in the rabbit uterus, but under in vitro culture conditions, constitutive PAF biosynthesis by isolated endometrial tissues is not easily demonstrable. Rapid metabolism of PAF relative to its synthesis may account for this disparity because we have recently shown that in stromal cells there is a significant build up of lyso-PAF suggesting that lyso-PAF-acetyl-CoA acetyltransferase might be a limiting factor. In the glandular epithelial cells however, the lyso-PAF build-up was replaced by a significant accumulation of a neutral lipid which was tentatively identified as 1-O-hexadecyl-2-acetylglycerol. It was hypothesized that, during endometrial growth and development, this lipid might serve as the substrate for the alkylacetylglycerol CDP-choline cholinephosphotransferase enzyme for PAF synthesis via the de novo pathway. We have therefore examined the activities of lyso-PAF:acetyl-CoA acetyltransferase and the CDP cholinephosphotransferase enzymes. Microsomal preparations containing lyso PAF:acetyl-CoA acetyltransferase activity catalyzed the incorporation of [3H]acetyl-CoA lyso-PAF into two distinct lipid products. One co-migrated with authentic PAF and the other with 1-O-hexadecyl-2-acetylglycerol, the latter being formed subsequent to PAF formation. The alkylacetylglycerol CDP-choline cholinephosphotransferase enzyme, which would potentially utilize the alkylacetylglycerol synthesized via the remodeling pathway, was also demonstrable. Unlike the species present in other tissues however, it was found to be sensitive to the presence of 10 mM DTT. The diacylglycerol CDP-choline cholinephosphotransferase species was also demonstrable and supported the synthesis of both PAF and phosphatidylcholine, in the absence of DTT, when only the synthesis of phosphatidylcholine was expected. It is hypothesized that the rabbit endometrium possesses active enzymes which may catalyze PAF synthesis via both the de novo and 'remodeling' pathways. PMID- 7780683 TI - Bimodal action of fatty acids on PMA-stimulated O2.- production in human adherent monocytes. AB - Not only unsaturated linear fatty acids, but also saturated monomethyl-branched fatty acids (MMBFAs), are provided by food. They are capable of penetrating into the membrane lipids and promoting lipid disorder. Both NADPH oxidase and protein kinase C (PKC) are bound to cell cytoplasmic membranes and are responsive to unesterified fatty acids (UEFAs). We found that the O2.- NADPH oxidase-mediated production of human adherent monocytes was modified by unsaturated linear and saturated branched UEFAs only in the presence of phorbol myristate acetate. This result together with our inhibition data indicated an action strictly linked to PKC activity. The type and intensity of action depended on the UEFA concentrations and chain structure. Nanomolar concentrations showed potentiating effects whereas micromolar (< CMC) concentrations displayed depressant influences MMBFAs were generally more active than the other FAs. With respect to the micromolar depressant effect, oleate and linoleate were as active and docosahexaenoate nearly as active as MMBFAs. As assessed by iso-15:0 or arachidonate action, such bimodal alteration did not occur in non-adherent monocytes and neutrophils. Certain UEFAs could be considered as 'cellular' anti oxidants on the sites of adherent-monocyte recruitment. PMID- 7780684 TI - Effect of a 5-lipoxygenase inhibitor, AL-3264, on propranolol-induced bronchoconstriction in guinea-pigs. AB - The administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We investigated the effect of AL-3264, a 5-lipoxygenase inhibitor, on propranolol-induced bronchoconstriction (PIB) after antigen inhalation in passively sensitized and artificially ventilated guinea-pigs. Our goal was to determine whether products of arachidonate 5-lipoxygenase are involved in such PIB. Bronchoconstriction occurred when 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. Pretreatment with AL-3264 given in intravenous doses of 0.01 and 0.1 mg/kg 15 min after the antigen challenge significantly reduced PIB in a dose-dependent manner. Pretreatment with 0.1 mg/kg of AL-3264 10 min before antigen challenge significantly inhibited both the immediate allergic bronchoconstriction and PIB, although the effect was minimal. Results suggest that arachidonate 5-lipoxygenase products (such as leukotriene B4, C4, D4 or E4) are involved in the pathophysiology of PIB but their contribution may be small. Further studies using selective antagonists for each of these leukotrienes are needed to clarify their role. PMID- 7780686 TI - T-cell depletion and manipulation in allogeneic hematopoietic cell transplantation. AB - Graft-vs-host disease (GVHD) in allogeneic hematopoietic transplantation can be abrogated by T-cell depletion (TCD) of the graft. Researchers have sought the optimal TCD procedure, which would alter the activity, number, and/or subpopulation profile of T cells to acceptable levels, while retaining sufficient engraftment potential of the harvested hematopoietic stem cells. The techniques that have successfully survived the translation from research studies into practical clinical application may be analyzed by their effectiveness, efficiency, ease of application, and cost. The predominant techniques rely on either physical separation of the T cell (binding to erythrocytes, lectins, centrifugation) or reaction with monoclonal antibodies (immunomagnetic, panning, complement-mediated cytotoxicity, immunotoxins). Comparative trials between the various techniques are few, making comparisons difficult. However, all of the techniques, whatever their relative advantages and disadvantages, must meet the same challenges. PMID- 7780685 TI - Inhibition of human group II phospholipase A2 by C-reactive protein in vitro. AB - Endotoxin or cytokine-induced expression of a secretory non-pancreatic phospholipase A2 (sPLA2) has been implicated in the pathogenesis of multisystem organ dysfunction or failure in patients with septic shock. Circulating sPLA2 levels increase as much as 1000-fold during the course of septic shock. However, the mode of regulation of the activity of this lipolytic enzyme is unknown, since circulating inhibitors have not been identified. We investigated the potential inhibitory activity of the acute phase reactant, C-reactive protein (CRP), a phospholipid-binding protein whose expression increases as much as 1000-fold during severe infections. Serum CRP and sPLA2 profiles were highly concordant in patients with septic shock. In studies in vitro, human CRP inhibited hydrolysis of PC-lyso-PC (2:1) multilamellar liposomes by human recombinant sPLA2 in a dose dependent manner, with an apparent IC50 of 50 micrograms/ml CRP and maximal inhibition at 100 micrograms/ml. Inhibition of sPLA2 activity by CRP was substrate concentration-dependent, and increasing substrate concentrations reversed the inhibitory effect of CRP using the PC-lyso-PC system. Preincubation of CRP with phosphorylcholine led to a concentration-dependent loss of CRP induced inhibition of substrate hydrolysis. These observations are consistent with a substrate-depletion model of inhibition of sPLA2 activity by CRP. PMID- 7780687 TI - Genetic marking and manipulation of hematopoietic progenitor cells using retroviral vectors. AB - In the 5 years since the first human gene therapy studies began, more than 70 clinical protocols have been approved, and over 200 patients have received genetically modified cells. A high proportion of these protocols have made use of hematopoietic progenitor cells or their mature progeny. In this review, we discuss the progress and limitations of current clinical gene transfer studies using marrow-derived progenitor cells and describe how the technique is being applied to the treatment of single-gene disorders and to augment cancer immunotherapies. We also discuss the contribution made by gene marking studies. PMID- 7780689 TI - Detection of minimal residual disease in autologous grafts. AB - There is increasing evidence that the presence of tumor cells within autologous hematopoietic cell grafts may increase the risk of relapse of disease post transplant. The sensitive detection of minimal residual disease is therefore central to improving the outcome of autologous transplantation, irrespective of the source of the graft. This review presents a comparative evaluation of the sensitivity and specificity of the currently available methods for tumor detection. PMID- 7780688 TI - Peripheral blood progenitor cell transplantation for hematological malignancies. AB - It has been demonstrated that it is possible to mobilize hematopoietic progenitor cells from the bone marrow into the peripheral blood, from which they can be collected by apheresis and used for transplantation. Although the clinical results obtained using this approach have not been compared in a randomized trial to those obtained using bone marrow, it appears that this method has certain advantages. These, together with future developments, are discussed in this review. PMID- 7780690 TI - Immunologically based methods for the elimination of tumor cells from autologous stem cell grafts. AB - There is currently renewed interest in the potential of tumor cells within autologous hematopoietic grafts to contribute to relapse of cancer post transplant. This has prompted the development of a wide variety of techniques for the ex vivo removal or purging of malignant cells from bone marrow and peripheral blood progenitor cell grafts. Both negative selection, in which tumor cells are eliminated, and positive selection, in which hematopoietic stem cells are enriched, are under examination as purging modalities. This review describes the use of immunologically based methods for autologous graft engineering. PMID- 7780691 TI - Cathepsin D in invasive ductal NOS, medullary, lobular and mucinous breast carcinoma. An immunohistochemical study. AB - Cathepsin D expression was determined by immunohistochemistry in 445 formalin fixed, paraffin embedded primary invasive breast carcinomas. We found: 1. a relationship between cathepsin D expression and histological type of tumour, 2. a negative correlation between cathepsin D expression and histological grade, 3. a negative correlation between cathepsin D expression and tumour diameter, 4. a relationship between the morphology of cathepsin D granules and histological type of the tumour. PMID- 7780692 TI - Flow cytometric evaluation of Ki67 proliferative antigen in primary breast cancer. AB - In the group of forty five primary mammary carcinomas Ki67 reactivity was evaluated with flow cytometry and immunohistochemistry. The expression of proliferative antigen, evaluated with both methods did not correlate with other indicators of proliferative activity. This result is probably associated with the physicochemical properties of breast cancer cells. PMID- 7780693 TI - Relationship of histology, DNA-values and proliferative activity in unselected breast cancer patients (a preliminary study). AB - Based upon a group of 108 consecutive mammary carcinomas a comparative analysis of morphological parameters, DNA-ploidy and indicators of proliferation activity was made. A correlation between Bloom-Richardson scale, mitotic index, PCNA labeling index and DNA-index was shown. The ploidy of mammary carcinomas was significantly related to the values of proliferative fraction, as well as to PCNA labeling index. Among patients with axillary metastases the tumor size and the value of PCNA-labeling index were significantly higher than those in patients with negative lymph nodes. PMID- 7780694 TI - Expression of synaptophysin and neurofilament protein confirms predominantly neuroblastic differentiation of primitive neuroectodermal tumors (PNET). AB - We report here that neuronal and glial differentiation is easily detected using synaptophysin (SF) and neurofilament protein (NFP) immunohistochemistry in primitive neuroectodermal tumors (PNET). Thus, for all practical reasons, every PNET should be regarded as PNET with "hidden" multipotential or bipotential differentiation. PMID- 7780695 TI - [The usefulness of morphologic methods for prognosis and treatment of breast carcinoma]. AB - Numerous parameters of prognostic and therapeutic importance can be assessed on the base of the morphological methods. Apart from the classic methods of examination, the immunomorphologic technics, cytometry and, recently, molecular biology technics, can be employed. The diameter of the primary tumor, as a basic parameter in assessment of the prognosis and therapy of breast cancer, can be linked with the group of attributes, defining differentiation, invasiveness, aggressiveness and a heterogeneous set of the other features. These parameters gain particular importance, when studied together with the clinical presentation of the disease. PMID- 7780696 TI - Reappraisal of ultrastructural diversity of amyloid plaques in Gerstmann Straussler-Scheinker syndrome. AB - Gerstmann-Straussler-Scheinker (GSS) syndrome is one of the most rare human neurodegenerative disease. In this report I summarise the ultrastructural pathology of amyloid plaques in two cases of this rare disease. The first type, unicentric "kuru" plaques consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a densely interwoven centre. Amyloid stars were surrounded by astrocytic processes and invaded by microglial cells. The amyloid bundles were attached to microglial cell membranes. Of note, robust basement membranes lined with electron dense astrocytic anchorages material were observed at the periphery of almost all amyloid plaques. Dystrophic neurites (DN) were seen only rarely. Occasionally, clusters composed of several kuru plaques were found; those are interpreted as intermediate forms to multicentric plaques which consisted of several merging stellate cores. In contrast to kuru plaques associated with a limited number of DN, numerous such structures were seen at the periphery of multicentric plaques. Identical DN were observed not associated with any plaques. The last and the rarest type of plaques, were purely neuritic plaques. These consisted of large areas filled with DN of different sizes and shapes (sometimes bizarre) but not amyloid bundles. Analogously to kuru and multicentric plaques, astrocytic processes were observed at the periphery. PMID- 7780697 TI - Diagnosis of Alzheimer's disease with commercially available anti-beta peptide (beta A4) antibodies following microwave oven pretreatment. AB - Alzheimer's disease (AD), the most common presenile dementia is underdiagnosed in Poland, thus every attempt to make the frequency of this diagnosis approaching standards of Western countries should be recommended. Deposits of beta A4 amyloid in a form of amyloid (senile) plaques, diffuse amyloid deposits and congophilic angiopathy is central to the pathogenesis of AD. These amyloid deposits are virtually invisible in routine pathological stainings like HE but may be visualized with Bielschowsky silver impregnation, other metallic impregnations, and following Thioflavine S or Congo red stainings. We report here that amyloid deposits are as easily immunolabeled with commercially available antibodies against beta A4 (DAKO) and such a staining was greatly enhanced by microwave oven pretreatment. In all cases of AD, the diagnosis could be easily made using either 4GM or commercial DAKO anti-beta A4 antibodies following pretreatment with formic acid or processing in microwave oven. Pretreatment in microwave oven even for only one second was already sufficient to visualize beta A4-immunopositive plaques while after 5 second the intensity of staining approached that obtained after formic acid pretreatment. PMID- 7780698 TI - Glycol methacrylate embedding of bone marrow cores. AB - The objective of the present study was to assess the use of glycol methacrylate (GMA) as an embedding medium for bone marrow biopsies. Paraffin-embedded bone marrow trephines, which are most widely used for diagnostic purposes, need to be decalcified prior to sectioning. This process has a number of effects, and results in interference with the evaluation of the bone marrow. Differentiation of some cases of hematological malignancies may be difficult in decalcified, paraffin-embedded bone marrow biopsy specimens, because of the reported inability to obtain reproducible blast counts, and because a considerable percentage of cells cannot be easily recognized. On the other hand, GMA-embedding of marrow cores, which obviates the need for decalcification, shows structural organization of the marrow and gives excellent cellular details. The simplicity of GMA embedding, short processing time and reproducibility, makes this method highly suitable for routine work in the hematology laboratory. PMID- 7780699 TI - Malignant blue nevus with neurosarcoma-like lymph node metastases. AB - We report a case of malignant blue nevus (MBN) of the foot with unusual morphologic presentation of nodal metastases. Their structure resembled neurosarcoma, and differed from the appearance of the primary tumor. This case confirms the mutual close histogenic relationship between MBN and neurosarcoma, both tumors originating from the structures of the neural crest. We also discuss the problem of so-called "benign" metastases of malignant melanoma. PMID- 7780700 TI - Chondrolipoma of the lip. A case report. AB - Chondrolipoma of the lip has been described. Only one case of the lesion in this region had been previously reported. PMID- 7780701 TI - Cardiac transplantation: a review. AB - Cardiac transplantation is currently a highly successful treatment for selected patients with end-stage cardiac failure. The long-term results are limited by the development of coronary artery vasculopathy, infection and malignancy. The activity of transplantation programmes worldwide is severely limited by the availability of donor organs. Further refinements of immunosuppressive agents are likely to result in improved prevention of both acute and chronic rejection. The donor pool is unlikely to be significantly extended as a result of measures to increase donor organ supply. Alternative methods to allograft transplantation need further investigation to increase the number of therapeutic options available for those patients with end-stage heart failure. PMID- 7780703 TI - Surgical treatment of thoracic aneurysm: a 5-year experience. AB - The surgical results of 77 patients with an aneurysm of the thoracic or thoracoabdominal aorta who were surgically treated during a 5-year period were retrospectively evaluated. Eighty-four operations were performed. The aneurysm was located on the ascending aorta in 20 patients, on the arch in nine, and on the arch and ascending aorta in eight. Sixteen aneurysms involved the descending thoracic aorta and 27 were thoracoabdominal. Associated surgery was performed in 12 patients. Deep hypothermia and circulatory arrest were employed in 30 patients. Partial cardiopulmonary bypass was used in 15 patients. Mortality was significantly higher if operation was performed under emergency conditions: the early mortality rate was 11.7%. Aggressive surgical management of untreated aneurysm is justified, as rupture of such lesions is the most common cause of death and associated mortality is high, with a 5-year survival rate of less than 20%. PMID- 7780702 TI - Arterial injuries associated with lower-extremity fractures. AB - The records of 110 patients with arterial injuries of the lower extremities associated with bone fractures, and managed in the authors' vascular surgery clinic, were reviewed. The majority (72%) were young men; 66 had blunt and 44 penetrating arterial injuries. A total of 92 patients were treated by saphenous vein interposition grafting, 12 with composite grafts and six with polytetrafluoroethylene grafts. The limb salvage rate was 93%. All eight amputations were in neglected cases with arterial injury at the popliteal or infrapopliteal level and associated with muscle loss. PMID- 7780704 TI - Results of an exclusion technique for treatment of abdominal aortic aneurysm. AB - An exclusion technique for the treatment of abdominal aortic aneurysm was used in six patients considered to be at high operative risk mainly because of chronic pulmonary disease. There were no deaths or immediate major complications. Thrombosis of the aneurysm was achieved in four of the six patients. However, in three cases, repeated percutaneous embolization was required to produce thrombosis. One patient developed a secondary rupture of a persisting infrarenal sac resulting from a patent inferior mesenteric artery. This patient was successfully managed by ligature of the infrarenal portion of the abdominal aorta through a median laparotomy. This study emphasizes the limits and the risks of the exclusion technique. PMID- 7780705 TI - Incidence of rupture of aortic aneurysms after coincidental operation. AB - The clinical course of 76 patients with aortic aneurysmal disease undergoing 107 coincidental surgical procedures was analysed in order to examine the relationship between aortic aneurysmal rupture and coincidental treatment. Additionally the incidence of aneurysmal rupture was assessed following 82 endoscopic procedures in 42 patients with aortic aneurysms. Two patients ruptured an aortic aneurysm after operation, one after colonoscopy (maximal transverse diameter 7 cm) and one after coronary artery bypass grafting (maximal transverse diameter 5.6 cm). The mean maximal transverse diameter of aneurysms in 76 patients was 5.08 cm (95% confidence interval 4.7-5.4 cm). Both patients with ruptured aortic aneurysm were outside these confidence limits and were known hypertensives whose perioperative control of hypertension was questionable. The present series of patients is discussed with reference to induction of collagenase activity as a precipitating cause for postoperative rupture of aortic aneurysms, perioperative control of hypertension, transverse aneurysm diameter as a predictor of postoperative rupture and conduct of coincidental procedures in the presence of aneurysmal disease. PMID- 7780706 TI - Management of neglected embolic occlusions in lower-limb arteries using arterial lavage. AB - Fourteen patients (seven males and seven females aged between 8 months and 100 years) with embolic lower-limb arterial occlusions of 1 to 6 days' duration were treated at Assir Central Hospital, Abha, Saudi Arabia over a 27-month period. On admission, the limbs were ischaemic up to mid-thigh and peripheral pulses were absent. Doppler studies showed absence of blood flow. The anatomical block was localized by angiography and ultrasonography. Fogarty catheter embolectomy was performed in all patients followed by rapid positive-pressure lavage of the vascular tree with 4-61 Ringer's lactate solution containing mannitol in an attempt to remove free radicals. Three patients died; one transmetatarsal amputation was performed. The remaining 11 limbs were salvaged and these patients remain ambulatory 21 to 42 months after surgery. PMID- 7780708 TI - Treatment plan used for vascular injuries in the Afghanistan war. AB - The outcome of 961 patients with vascular injuries received in the Afghanistan war is reported. Some 755 (78.6%) patients had to have a primary amputation while only 206 (20.9%) had restorative surgery. The vessels were simply ligated in 85 cases and reconstructive surgery was performed in 121. Ligation resulted in 46 (54%) cases of limb salvage and functional restoration; 30 (35%) went on to amputation and nine (11%) died. Of the 121 patients treated by reconstructive surgery, 83 (68.5%) had completely patent vessels, 19 (15.7%) collateral compensation, 13 (10.7%) proceeded to subsequent amputation and six (4.9%) died. Although the location of the injury and the duration of the ischaemic period are important in deciding how to treat the vascular injuries of war, the decisive factor appears to be the pre-existing severity of regional ischaemia. PMID- 7780707 TI - Iatrogenic vascular injuries in western Saudi Arabia. AB - A group of 30 consecutive patients with iatrogenic vascular injury were studied to determine the aetiology of the condition and to investigate its possible prevention. Of the patients, 18 were males and 12 females; mean age was 37.0 years (range 2 weeks to 70 years). Most injuries (n = 25) involved the arterial system; eight cases (27%) were recognized during the operative procedure. The most common presentations were bleeding and chronic ischaemia. Cannulation of vessels was the cause of injury in 14 cases (47%); two-thirds of these were iatrogenic in nature. A conservative policy was adopted in nine patients; surgery was planned but not performed in two. A total of 19 patients were operated on (17 reconstructions, one ligation, one fasciotomy); two died from causes related to their original condition. In order to reduce the incidence of iatrogenic injury, medical personnel should be informed of possible vessel damage, especially during cannulation. All surgical and radiological procedures should be carefully audited. PMID- 7780709 TI - Infrainguinal arterial reconstruction in end-stage renal disease. AB - A total of 14 infrainguinal revascularizations in 11 patients with end-stage renal disease resulting from diabetes mellitus were reviewed. Indications for surgery comprised gangrene or non-healing ulcerations in eight patients (11 limbs), ischaemic rest pain in two (two limbs) and disabling claudication in one (one limb). No graft failures occurred during the period of observation. There were two immediate postoperative deaths, one amputation, and four persistent non healing foot ulcers. The remaining four patients showed improvement. Six deaths occurred, including two perioperative deaths. Four patients with non-healing ulcers died within 1 year and 10 months after revascularization, but their deaths were not associated with the foot ulcers. The cumulative patient survival rate was 42% at 1 year. Infrainguinal revascularization in patients with end-stage renal disease caused by diabetes mellitus is feasible when meticulous preoperative assessment and careful perioperative management are employed to minimize operative risk. PMID- 7780710 TI - Short-term and long-term outcome following renovascular reconstruction. AB - Experience with renovascular reconstruction at the authors' institution over the past 16 years has been reviewed. A total of 76 patients underwent surgical intervention for renovascular disease during that time. This included 62 patients with atherosclerosis and 11 with fibromuscular hyperplasia. Indications for intervention were uncontrolled hypertension in 42 patients and to restore renal impairment in eight. The procedure was performed for both indications in 26 patients. Ten patients (13%) died in the perioperative interval, which correlated strongly with comorbidity. With the exception of one patient, all deaths occurred in the elderly (> 65 years). While an increased mortality rate (P < 0.05) was observed in those undergoing concomitant surgical procedures (20%) as opposed to those undergoing renovascular reconstruction alone (6%), this was not an independent risk factor. Both the short term and long term response of hypertension control to renovascular reconstruction were favourable, with age < 60 years, shorter duration of hypertension (< 5 years) and diagnosis of fibromuscular hyperplasia predictive of a better response. Renovascular reconstruction, while successful in stabilizing or even improving renal function in the short term, was poor at restoring function long term, especially in the subgroup of patients whose serum creatinine was > 200 mumol/l at the time of reconstruction. PMID- 7780712 TI - Anomalous carotid vertebral anastomoses and carotid endarterectomy. PMID- 7780714 TI - Doppler analysis of the left venting line: an effective and simple technique to control heart de-airing. AB - Air embolism is still a major risk of open-heart surgery. Different techniques of air removal have been established, even though none is completely effective. Since 1989 the authors have used a new technique to avoid air passage into the left vent line when the left heart cavities are open. A specially designed probe attached to a vascular Doppler analyser is fixed to the left vent tubing. Air passage is detected by a characteristic acoustic signal. Air removal procedures are continued until no audible signals are detected. This technique was carried out in 150 open left heart operations in which there were no clinical signs of air embolism. To validate this procedure, simultaneous assessment of air removal was made using transoesophageal echocardiography (TEE) and carotid Doppler (CD) in six patients. When Doppler signs of air in the left vent disappeared, TEE revealed that a small amount of air was still present in two patients; carotid Doppler showed only minimal passage of air bubbles in three patients after left vent removal while the heart was freely ejecting. These results demonstrate that this technique is a reliable method of assessing air removal, which is especially useful when de-airing is difficult during reoperation. PMID- 7780713 TI - Congenital aneurysm of the internal jugular vein in a pregnant woman. AB - A pregnant woman with a symptom-free congenital aneurysm of the internal jugular vein (IJV) is described. A color duplex scan revealed an aneurysm (2.4 cm in diameter) of the right IJV in the mid-neck without evidence of thrombus. To the authors' knowledge, this is the first reported case demonstrating that such a lesion in a pregnant woman can be safely managed without excision. PMID- 7780711 TI - Diffuse arterial thrombosis in a young man with elevated lipoprotein(a) and minimal atherosclerosis. AB - An increased incidence of premature atherosclerotic arterial occlusive disease was recently reported in young adults. This condition is characterized by early occurrence of severe symptoms, lower incidence of typical cardiovascular risk factors for atherosclerosis, different natural course of arterial disease vis-a vis older population, and poor outcome of a standard treatment. This report describes a young man with aggressive arterial occlusive disease in the lower extremities and symptom-free occlusions of coronary and renal arteries in association with high levels of lipoprotein(a). Microscopic early atherosclerotic changes were noted in the occluded arteries of the amputated leg. Premature atherosclerotic arterial occlusive disease in young adults has different clinical and pathological patterns, necessitating a different approach for evaluation and treatment. PMID- 7780717 TI - Concomitant repair of complete atrioventricular canal defect and transposition of the great arteries in an infant. AB - The case of an infant who was born with the rare presentation of complete atrioventricular canal defect and transposition of the great arteries is described. The patient underwent pulmonary banding at the age of 2 months, followed by concomitant arterial switch and repair of the atrioventricular canal defect at 20 months. Palliative banding allowed for the infant to grow and thus facilitated the later successful repair of these congenital defects. PMID- 7780716 TI - Left aortic arch and right descending aorta--interruption or severe coarctation of the aortic arch in the newborn. AB - Three consecutive neonates (aged 7, 14 and 30 days, body-weight 2980 g, 3000 g and 3400 g respectively) with interruption of the aorta (n = 2) and severe coarctation (n = 1) in the presence of left aortic arch and right descending aorta are reported. Associated lesions were an aortopulmonary window in the first case and an unrestrictive ventricular septal defect in the two others. Intractable heart failure and the complexity of the malformation led to the decision of a staged operation. A prosthetic graft was interposed between the ascending and descending aorta via a right thoracotomy in order to bridge the atretic or hypoplastic segment without using extracorporeal circulation. There was no intraoperative complication. One patient developed a thrombocytopenia within the frame of a sepsis syndrome and died on day 5 after operation, death being caused by a massive bleeding into the left thoracic cavity, although the operation was carried out via a right thoracotomy. Angiography 1 year after operation revealed a good flow through the grafts and no stenosis at the site of the anastomoses. The two surviving infants are clinically well without any medication. The reported operative technique provides an alternative palliative possibility to manage critically ill neonates without any obstacle to later definitive repair. PMID- 7780715 TI - Balloon angioplasty before Wheat's operation in a patient with Turner's syndrome. AB - The case of a 19-year-old woman with Turner's syndrome, dissecting aneurysm of the ascending aorta, coarctation of the aorta and bicuspid aortic valve stenosis is presented. Balloon angioplasty was performed before surgery to relieve the pressure gradient caused by coarctation of the aorta. Successful surgical treatment was carried out using Wheat's method. Four-year follow-up has revealed no signs of complications such as restenosis or aneurysm formation. PMID- 7780718 TI - Anomalous origin of the right coronary artery from the pulmonary artery: an unusual cause of angina. AB - Origin of the right coronary artery from the pulmonary trunk rather than the aorta is a rare congenital anomaly. Only five cases of this anomaly have presented with signs and symptoms of ischemia. One of these cases, along with objective evidence for the cause of the ischemia and recommendations regarding surgical repair, is presented here. PMID- 7780720 TI - Acute postoperative obstruction of the ascending aorta following replacement with an intraluminal graft. AB - A fourth case of displacement of one ring of an intraluminal graft is reported. This occurred in a woman who was operated on for acute dissection of the aorta. The displacement happened 8 h after surgery and produced acute obstruction of the ascending aorta. Restoration of the proximal ring of the graft into its correct position was successful. PMID- 7780719 TI - Prevention of left ventricular thrombus formation during pneumatic pump assist. AB - A postcardiotomy patient with a pneumatic pulsatile pump for left ventricular assist showed a smoke-like swirling echo within the left ventricle during pump assist. The image disappeared partially during intra-aortic balloon pumping, which was performed as usual. Subsequently, three pumps (native left ventricle, pneumatic and intra-aortic balloon) were driven synchronously; that is, the ventricular assist pump ejected the blood in the first half of the diastole of the native heart beat, and the intra-aortic balloon was inflated during the second half. With this bisected diastolic driving, the abnormal echo disappeared completely. The patient died 52 days after operation, but no thromboembolic episode was observed during the course, and no fresh thrombus was found within the left ventricle at autopsy. The bisected diastolic driving method served as an aid to prevent stagnation of blood and thrombus formation within the native left ventricle in this patient with a left ventricular assist device. PMID- 7780721 TI - Comparative investigations among meteorological conditions, air chemical-physical pollutants and airborne particulate mutagenicity: a long-term study (1990-1994) from a northern Italian town. AB - The findings of a continuos monitoring (Apr90-Mar94) on urban air quality of a Po Valley town are reported. Chemical-physical and genotoxicity data were detected. The results show the presence of mutagenic agents during the whole investigated period. Short term mutagenesis tests together with chemical-physical parameters analysis are able to better assess air quality and genotoxic risk for the population. PMID- 7780722 TI - The use of in vitro DNA adduct formation to estimate the genotoxicity of residues at contaminated sites. AB - Genotoxic carcinogens such as polycyclic aromatic hydrocarbons (PAHs) covalently bind to the bases in DNA to form adducts. The formation of DNA adducts is significant with respect to chemical carcinogenesis. Many contaminated sites contain quantities of carcinogens such as PAHs, and the evaluation of the genotoxicity of these soils has important implications for human risk assessment. DNA adducts can be formed using an in vitro system incorporating extracts from contaminated soils. The 32P-postlabelling assay is a sensitive technique for the detection of DNA adducts from complex mixtures of environmental carcinogens. These techniques have been used to form and detect DNA adducts using soils from a number of coal gasworks sites. The results show that the extent of adduct formation depends partially on the petroleum hydrocarbon content of samples, but also on other undetermined factors related to composition. While environmental weathering has been shown to effect the PAH composition of samples, this is not an important factor in controlling the genotoxicity of samples as estimated by DNA adduct formation. PMID- 7780724 TI - Learning. A mechanism of learning found? AB - Synaptic plasticity in the cerebellar cortex is abolished and cerebellum dependent motor learning is decreased in mice lacking a metabotropic glutamate receptor. Is the receptor involved in learning? PMID- 7780725 TI - Cartilage disorders. The importance of being sulphated. AB - Mutations within a gene encoding a novel sulphate transporter cause diastrophic dysplasia. This finding has implications for the management of the disorder and for understanding the structure and function of cartilage. PMID- 7780726 TI - Intercellular signaling. A kinase for cell-fate determination? AB - GSK-3, a ubiquitous kinase regulated by tyrosine phosphorylation, controls cell fate decisions in both Drosophila and Dictyostelium; genetic analysis of its interactions with other signaling pathways is now possible. PMID- 7780723 TI - Congener specific analysis of polychlorinated biphenyls (PCBs) in serum using GC/MSD. AB - A new congener specific method has been developed for extraction and quantitative determination of PCB contaminants of serum. After liquid-liquid extraction and chromatographic fractionation with Carbopack-C/florisil column, the analytes were identified and quantified utilizing gas chromatography/mass spectrometry (GC/MSD) using selected ion monitoring (SIM) technique. Recoveries of 35 non-planar PCB congeners (#18, 28, 31, 44, 49, 52, 60, 66, 74, 82, 87, 99, 101, 105, 110, 114, 118, 128, 138, 141, 146, 151, 153, 156, 157, 158, 167, 170, 171, 180, 183, 185, 187, 189 and 194) and 5 non-ortho (coplanar) congeners (#37, 77, 81, 126 and 169) from spiked serum were between 55-115%. PMID- 7780727 TI - Neural development. Brain stems. AB - The discovery of stem cells in adult nerve tissue makes the repair of brain damage a realistic possibility. PMID- 7780728 TI - Superantigens. Gazing into the crystal ball. AB - The recently determined crystal structures of complexes between bacterial toxin 'superantigens' and MHC class II molecules shed light on the nature of the interactions between these two molecules. PMID- 7780730 TI - Regulated secretion. Helper proteins for neuroendocrine secretion. AB - The granins, known to be general constituents of neuroendocrine secretory granules, are regulators of the proteolytic processing of peptide precursors and promote their aggregation-mediated sorting into secretory granules. PMID- 7780732 TI - Intraepithelial lymphocytes. Scratching the surface. AB - The epithelial surface is the site at which we first encounter pathogens. Two recent advances indicate that intraepithelial lymphocytes use specialized tools to help protect this surface. PMID- 7780731 TI - Emotional learning. Fear and loathing in the amygdala. AB - The amygdala in the brain plays a critical role in learning emotional components of experience, such as conditioned fear; these processes in turn affect many other aspects of memory and cognition. PMID- 7780729 TI - Chromatin. Ga-ga over GAGA factor. AB - Recent results suggest that the Drosophila transcriptional activator known as GAGA factor functions by influencing chromatin structure. PMID- 7780733 TI - Molecular evolution. Retroposon revivals. AB - Phylogenetic studies of the mouse L1 retroposon family show that the elements evolve through successively active subfamilies, which differ from each other by complete replacements of their promoter sequences. PMID- 7780734 TI - Neural transmission. Synaptotagmin is just a calcium sensor. AB - Ligand-binding studies have suggested many functions for the synaptic vesicle protein, synaptotagmin. But genetic elimination of the protein supports only one role: translating arriving Ca2+ signals into vesicle release. PMID- 7780735 TI - Genetic hypertension. A direct link to salt. AB - The basis of one type of inherited hypertension has been discovered-it is caused by mutations in the gene for the beta subunit of a renal sodium channel. PMID- 7780736 TI - Green fluorescent protein. The green revolution. AB - Green fluorescent protein allows gene expression and protein localization to be observed in living cells. PMID- 7780737 TI - Structural characterization of viral fusion proteins. AB - Infection by enveloped viruses is initiated by the fusion of viral and cellular membranes. In many cases, the viral membrane proteins that mediate fusion must undergo conformational changes to become active. Influenza hemagglutinin, for example, is activated by a dramatic conformational rearrangement, triggered by the low pH of the intracellular compartment in which fusion occurs. Structural characterization of this rearrangement has led to a reconsideration of how hemagglutinin mediates membrane fusion. PMID- 7780738 TI - A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. AB - BACKGROUND: p21WAF1 is a potent inhibitor of the cell-cycle regulatory cyclin dependent kinases (Cdks). It acts on Cdks in the G1 and S phases of the cell cycle, and also binds to proliferating cell nuclear antigen (PCNA), blocking DNA replication in vitro. Transcription of p21WAF1 can be induced by the human tumour suppressor protein p53, suggesting that the action of p21WAF1 may be important in cancer prevention. We have investigated the interaction between p21WAF1 and PCNA using a genetic two-hybrid screen and with arrays of synthetic peptides derived from the p21WAF1 protein sequence. RESULTS: We have established that the carboxy terminal region of p21WAF1 interacts with PCNA in a yeast two-hybrid screen. Interaction with p21WAF1 involves the central loop of PCNA, which connects the two domains of the PCNA monomer. The interaction was finely mapped using peptides derived from the entire sequence of the p21WAF1 protein, and the critical residues were found to be QTSMTDFY (amino acids 144-151 of p21WAF1). Remarkably, a 20-residue peptide containing this sequence inhibited replication of simian virus 40 (SV40) DNA in vitro and could capture PCNA from whole cell extracts, demonstrating that small molecules can retain the biological activity characteristic of the whole protein. Sequential alanine-scan mutations of the peptide demonstrated that its ability to block replication correlates with its affinity for binding PCNA. CONCLUSIONS: We have shown that PCNA and the cell cycle regulator p21WAF1 interact in vivo, and that this interaction requires the central loop of PCNA and an eight amino-acid motif from the carboxyl terminus of p21WAF1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780740 TI - Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases. AB - BACKGROUND: Non-receptor protein-tyrosine kinases often contain at least one Src homology 2 (SH2) domain, a protein module that binds with high affinity to tyrosine-phosphorylated peptides. Because SH2 domains would be predicted to bind with high affinity to proteins phosphorylated by the kinase, but not to the unphosphorylated substrate, their presence in tyrosine kinases has been puzzling. An important role for the SH2 domain of the Abl tyrosine kinase was suggested by work showing that Abl requires an intact SH2 domain in order to malignantly transform cells, and that replacement of the Abl SH2 domain with heterologous SH2 domains alters the spectrum of proteins phosphorylated detectably by Abl in vivo. RESULTS: We have used purified wild-type and mutant Abl kinases to examine the roles of the Abl's SH2 and catalytic domains in phosphorylation of p130CAS, a model substrate that has multiple potential phosphorylation sites. We find that an SH2 domain is required for efficient hyperphosphorylation of p130 in vitro. We use chimeric mutants with heterologous SH2 domains to demonstrate that the SH2 domain of the oncogenically transforming adaptor protein Crk, which is the SH2 domain predicted to bind with highest affinity (of those tested) to potential phosphorylation sites in p130, is best able to facilitate hyperphosphorylation. This is the case whether the catalytic domain of the kinase is derived from Abl or from its distant relative, Src. These studies also reveal a role for binding of Crk to Abl in mediating phosphorylation by the kinase. Using purified proteins, we demonstrate that association with Crk strikingly enhances the ability of Abl to hyperphosphorylate p130. There is an excellent correlation between the ability of mutant Crk proteins to promote hyperphosphorylation of p130 by Abl and their ability to transform rodent fibroblasts. CONCLUSION: Our data suggest that, ultimately, the substrate specificity of a non-receptor tyrosine kinase is dependent on the binding specificity of its associated SH2 domain. The SH2 domain binds tightly to a subset of proteins phosphorylated by the catalytic domain, leading to processive phosphorylation of those proteins. Substrate specificity can be broadened by an association between the kinase and proteins, such as Crk, that contain additional SH2 domains; this may play a role in malignant transformation by Crk. PMID- 7780741 TI - Heat-shock proteins Hsp104 and Hsp70 reactivate mRNA splicing after heat inactivation. AB - BACKGROUND: The heat-shock protein Hsp104 plays a crucial role in the survival of cells exposed to high temperatures and other severe stresses, but its specific functions and the biological pathways on which it operates have been unclear. Indeed, very little is known about the specific cellular processes in which any of the heat-shock proteins acts to affect thermotolerance. One essential process that is particularly sensitive to heat in many organisms is the splicing of intervening sequences from mRNA precursors. RESULTS: We have examined the role of Hsp104 in the repair of splicing after disruption by heat shock. When splicing in the budding yeast Saccharomyces cerevisiae was disrupted by a brief heat shock, it recovered much more rapidly in wild-type strains than in strains containing hsp104 mutations. Constitutive expression of Hsp104 promoted the recovery of heat damaged splicing in the absence of other protein synthesis, but did not protect splicing from the initial disruption, suggesting that Hsp104 functions to repair splicing after heat damage rather than to prevent the initial damage. A modest reduction in the recovery of splicing after heat shock in an hsp70 mutant suggested that Hsp70 may also function in the repair of splicing. The roles of Hsp104 and Hsp70 were confirmed by the ability of the purified proteins to restore splicing in extracts that had been heat-inactivated in vitro. Together, these two proteins were able to restore splicing to a greater degree than could be accomplished by an optimal concentration of either protein alone. CONCLUSIONS: Our findings provide the first demonstration of the roles of heat-shock proteins in a biological process that is known to be particularly sensitive to heat in vivo. The results support previous genetic arguments that the Hsp104 and Hsp70 proteins have different, but related, functions in protecting cells from the toxic effects of high temperatures. Because Hsp104 and Hsp70 are able to function in vitro, after the heat-damaged substrate or substrates have been generated, neither protein is required to bind to its target(s) during heating in order to effect repair. PMID- 7780739 TI - Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines. AB - BACKGROUND: Mitogen-activated protein (MAP) kinase is central to a signal transduction pathway that triggers cell proliferation or differentiation. Activation of the p42mapk isoform requires its phosphorylation at two residues, Thr 183 and Tyr 185, and this phosphorylation is catalysed by MAP kinase kinase (MAPKK). Relatively little is known, however, about the enzymes that dephosphorylate these residues, thereby inactivating the pathway. Recently, the CL100 phosphatase has been shown to inactivate p42mapk in vitro by dephosphorylating Thr 183 and Tyr 185 at similar rates. CL100, the product of an immediate early gene, is synthesized within one hour of stimulating cells with growth factors or exposure to oxidative stress or heat shock. Incubation of NIH 3T3 fibroblasts with cycloheximide prevents both synthesis of CL100 and inactivation of p42mapk after stimulation with serum. RESULTS: Depleting cells of CL100 and preventing its induction using cycloheximide stopped the inactivation of p42mapk in Swiss 3T3 fibroblasts following stimulation with epidermal growth factor (EGF), but had no effect on the rapid inactivation of p42mapk in response to EGF in adipose (3T3-L1) or chromaffin (PC12) cells or in response to platelet derived growth factor (PDGF) in endothelial (PAE) cells. Moreover, maximal induction of CL100 mRNA and a CL100-like activity did not trigger inactivation of p42mapk, which was sustained at a high level after stimulation of PC12 cells with nerve growth factor, PAE cells with serum, or Swiss 3T3 cells with PDGF. Dephosphorylation of Tyr 185 but not Thr 183 of p42mapk was suppressed by vanadate in EGF-stimulated PC12 cells; dephosphorylation of Thr 183, by contrast, was elicited by a vanadate-insensitive activity. Protein phosphatase-2A was the only vanadate-insensitive phosphatase acting on Thr 183 of p42mapk or on MAPKK to be detected in PC12 cell extracts. Phosphorylation of Thr 183 also inhibited the dephosphorylation of Tyr 185 in vitro by the major vanadate-sensitive Tyr 185 specific phosphatase, explaining why dephosphorylation of Thr 183 is rate limiting for p42mapk inactivation in PC12 cells after stimulation with EGF. CONCLUSIONS: The rapid inactivation of p42mapk initiated five minutes after stimulation of endothelial, adipose and chromaffin cells with growth factor is not catalysed by CL100, but rather by protein phosphatase 2A and by a protein tyrosine phosphatase distinct from CL100. Induction of CL100 is not accompanied by the inactivation of p42mapk in a number of situations. PMID- 7780742 TI - Function and characteristics of repetitive calcium waves associated with meiosis. AB - BACKGROUND: Internal calcium waves and oscillations are now recognized as universal features of cellular activation, but their exact role remains uncertain. In mammalian and ascidian eggs, a large, sperm-triggered calcium activation wave crosses the egg at fertilization, followed by a series of periodic increases in intracellular calcium concentration ([Ca2+]i). We have previously shown that, in eggs of the ascidian Phallusia mammillata, these periodic, post-activation [Ca2+]i increases are in the form of waves, the origin of which relocalizes to a pacemaker region, and that they stop seconds before the completion of meiosis. RESULTS: We show here that the origin of the first one to four post-activation calcium waves in P. mammillata eggs transfers progressively from the site of sperm entry, usually in the animal hemisphere, towards an endoplasmic reticulum (ER)-rich contraction pole in the vegetal hemisphere, a process that takes about five minutes. Once the origin of these repetitive post activation calcium waves has reached the contraction pole, all subsequent calcium waves originate from the domain of ER concentrated there, which acts as a pacemaker. The first few post-activation calcium waves are faster than the activation wave and, like the activation wave, they propagate homogeneously throughout the cytoplasm. Approximately five to ten minutes after fertilization, the post-activation calcium waves begin to propagate preferentially in the egg cortex. By manipulating intracellular calcium levels with caged inositol 1,4,5 trisphosphate (InsP3) and a competitive inhibitor of InsP3-induced calcium release, we show that the activation wave induced by the sperm is sufficient to induce extrusion of the first polar body, but that additional [Ca2+]i increases are necessary for completion of the second meiotic division. However, periodic calcium waves per se do not seem to be strictly necessary for the completion of meiosis, as a persistent and homogeneous increase in calcium, induced by the calcium ionophore ionomycin, is sufficient to cause second polar body formation and allow completion of meiosis on time. CONCLUSION: These results clearly show that, in the ascidian egg, post-activation calcium waves are required to complete meiosis. They also show that following a period of progressive relocalization of the wave origin, which lasts approximately five minutes, an ER-rich domain at the contraction pole finally becomes a pacemaker from which the calcium waves originate. Once their origin becomes stably localized, the calcium waves begin to propagate preferentially around the cortex of the egg rather than throughout the egg cytoplasm. PMID- 7780743 TI - Loose ends. PMID- 7780745 TI - PDA comments. "Review of general biologics licensing regulations". Parenteral Drug Association. PMID- 7780744 TI - Elaborate decision criteria for media fill tests. PMID- 7780746 TI - PDA response. "Guideline for submitting documentation for sterilization process validation in applications for human and veterinary drug products". Parenteral Drug Association. PMID- 7780747 TI - Microbial retention characteristics of 0.2-microns-rated nylon membrane filters during filtration of high viscosity fluids at high differential pressure and varied temperatures. AB - Regulatory guidelines for aseptic manufacture of pharmaceuticals recommend validation of sterilizing filters by bacterial challenge under "worst case" conditions. The microbial retention characteristics of a sterilizing grade, 0.2 microns-rated Nylon 66 membrane filter were evaluated for filtration of high viscosity fluids. Glycerol (80%) was used as the carrier fluid and Pseudomonas diminuta ATCC 19146 as the challenge organism. Testing was carried out at a constant differential pressure of 60 psig over a six-hour test period. Test runs were undertaken at three different temperature conditions (25 +/- 5 degrees C, 42 +/- 1 degree C, and 50 +/- 1 degree C). Under the test conditions, the Nylon 66 membranes provided total retention of P. diminuta. The results demonstrated that a high pressure differential challenge using a high viscosity fluid over a six hour test period at ambient and elevated temperatures did not alter the retention characteristics of the membrane filter. PMID- 7780748 TI - Particle size reduction of emulsions by formulation design-II: effect of oil and surfactant concentration. AB - The objective of this study was to investigate the effect of the concentration of surfactant and oil on particle size reduction and stability of oil-in-water emulsion formulations containing polyhydroxy alcohols. Emulsions were prepared using an emulsifier system consisting of Tween 80 and Span 80 with 5%, 10%, 15% and 20% soybean oil and containing 50% w/w of either propylene glycol (PG) or glycerol (GLY) in the external phase. At each oil concentration, four emulsions were formulated with increasing surfactant concentration to provide emulsions with surfactant to oil (S/O) ratios of 0.1, 0.2, 0.3 and 0.4. Three parameters were evaluated, particle size reduction, particle size stability upon dilution, and viscosity. It was found that increase in S/O ratio resulted in substantial decrease in particle size in all cases. But there was a difference in the particle size reduction pattern between PG and GLY. Increase in oil concentration at the same S/O ratio caused particle size reduction for emulsions with PG but not for emulsions with GLY. The reduction in particle size was also greater for emulsions containing PG. Further, particle size of emulsions containing PG was found to be stable over 24 hours after dilution. However, a slight increase in particle size was observed in emulsions containing GLY. It was also found that the viscosity of emulsions increased with an increase S/O ratio as well as the concentration of the oil. PMID- 7780749 TI - The effect of aggregation inhibitors and antioxidants on the stability of hemin solutions. AB - Despite their importance as infusions for the treatment of porphyrias, aqueous solutions of hemin can be quite unstable, with a reported half-life of a few hours. We have examined factors which affect the stability of hemin solutions in order to identify possible excipients and conditions which would increase the stability. In agreement with previous reports, we have found that human serum albumin leads to stabilization of hemin solutions; polyvinylpyrrolidone is also an effective stabilizer of hemin. Imidazole, caffeine, and niacinamide were also found to stabilize hemin, apparently by complexing to hemin and preventing the formation of hematin dimers. Addition of certain antioxidants, e.g., butylated hydroxyanisole and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), led to stabilization of hemin, suggesting that radicals are involved in the degradation process. A comparison was also made by HPLC analysis of the hemin autooxidation products with those from the reaction of hemin with hydrogen peroxide; the results indicate that the products are similar but not identical. The implications of the results for clinical use of hemin solutions are discussed. PMID- 7780750 TI - Gamma processing technology: an alternative technology for terminal sterilization of parenterals. AB - This paper will outline the advantages of utilizing gamma radiation as a means for terminally sterilizing parenterals and other pharmaceutical products. The factors which must be evaluated in order to qualify a product for radiation sterilization will be detailed. It will also compare the characteristics of this method with other technologies currently available. The highest SAL can be achieved by combining a knowledge of the microbial quality of the raw materials, and the manufacturing environment with a formulation designed to promote the most radiation stable form of the product. PMID- 7780751 TI - What do we mean by "sterility"? AB - In a "President's Comment" (PDA Newsletter, August 1993) James Akers referred to such numbers, and numerical statements, as: 10(-3), 10(-6), 1cfu/m3, 3cfu/Rodac plate, 90 feet per minute, 0.005 inches of water, 80 degrees C, 20 air changes per hour, and 0.1% with 95% level of confidence. He posed the question "Where did all these numbers come from?" These are, of course all numbers instantly recognisable by those acquainted with the art and science of parenteral manufacture. They are accepted (essential?) parameters of various aspects of this process. But Akers's question carries with it the implicit answer: "They just seemed like a good idea at the time." One might similarly add: 100, 10,000, 100,000, 115 degrees C for 30 minutes, 121 degrees C for 15 minutes, and so on. PMID- 7780753 TI - Travelling with your baby. PMID- 7780752 TI - Qualification of weighing station for pharmaceutical substances. AB - Work at weighing stations in pharmaceutical industries can cause risk situations to the operators as well as to the product. When working at a station, the operators' movements and the interaction between air movements and dispersion of contaminants play a vital role. A newly designed ventilated weighing station with HEPA-filters and how it can be evaluated with tracer gas will be discussed. PMID- 7780754 TI - How do women choose to breastfeed? AB - Midwives generally rely on client education to get the message across that 'breast is best'. Research tends to ask why women bottlefeed rather than trying to find out how the decision to breastfeed is reached. The psychological theory of personal constructs might help to shed light on this difficult and frustrating area of midwifery. PMID- 7780755 TI - The principles of antenatal screening. PMID- 7780756 TI - Is active management always necessary? AB - There is a conflict between the active management (AM) of labour and the woman centred approach advocated by Changing Childbirth. AM assumes that all births are abnormal until proved normal, whereas midwives usually assume the opposite. There is evidence that AM can be ineffective in shortening labour. Midwives should consider alternative, non-medical approaches to active management. PMID- 7780757 TI - Our best chance ever. Interview by Alison Turnbull. PMID- 7780758 TI - Ethical issues in qualitative studies. AB - Research interviews can expose individuals' inner thoughts and beliefs. The researcher must consider the participants' interests. Those interests might be best served by a well thought-out scheme for ensuring anonymity. The researcher must guard against inadvertent clues to participants' identity, through well known individual views or language idiosyncrasies. Ownership of data must be considered. Ethically speaking, permission to undertake research does not automatically grant permission to publish the results. PMID- 7780759 TI - A midwifery team for high-risk pregnancies. AB - A midwifery group practice approach has been developed for the care of high-risk mothers at the Chelsea & Westminster Hospital. The team of six midwives working with the professor of obstetrics, the consultant obstetrician and a physician cares for a caseload of 200 high-risk women a year. Midwives are able to acquire and maintain the skills necessary to care for high-risk mothers. Audit of the scheme is essential and will be complemented by a satisfaction survey completed by clients, midwives and doctors. PMID- 7780760 TI - Hopes for the future of midwifery care. PMID- 7780762 TI - Only plumbers? PMID- 7780761 TI - Shortchanging childbirth. PMID- 7780763 TI - Bournemouth puts breastfeeding first. PMID- 7780764 TI - Six-point plan for supervision. PMID- 7780765 TI - The clinical and statistical significance of using norm- versus criterion referenced measures. PMID- 7780766 TI - Use of the cognitive assessment method to evaluate the adequacy of sexually transmitted disease history questions. AB - Cognitive assessment is an approach used to evaluate questions in survey interviews. This approach is useful in delineating measurement error due to participants' understanding of terms and interpretation of questions. The purpose of this study was to evaluate the quality of questionnaire items designed to evaluate history of sexually transmitted diseases (STDs) using a cognitive assessment approach. Participants recruited from an STD clinic were asked up to six questions to assess their history of STDs. Verbal probes were used after each question in an attempt to evaluate the participants' understanding of the questions and methods they used to recall episodes of having STDs. The findings revealed that respondents did not understand the medical terms for some STDs, that the wording of one question potentially interfered with respondents' comprehension of the question, and that respondents used an episodic recall method to determine their number of previous STD infections. Cognitive assessment is a useful method for identifying potential sources of respondent-induced measurement error. PMID- 7780767 TI - Cognitive appraisal of stress events: measuring the personal schema of childbirth. AB - The purpose of this study was to theoretically base, develop, and test items for the Childbirth Schema Scale. The scale was designed to obtain an understanding of schema formation and revision with the known stressor of childbirth. The psychometric properties of the instrument were assessed using a sample of childbearing women, surveyed before and after birth. A principal components analysis with varimax rotation resulted in a four-factor solution supporting the theoretical factors of emotions of outcome, sensations of work, time, and preparation for control. Construct validity was assessed by hypothesis testing that women whose prebirth schemas were least like their real experience would use more review than women whose schemas were closer. A significant t test between the two groups provided some evidence of validity. The factors were used to form subscales. Internal consistency scores for each subscale were .73, .70, .84, and .65, respectively. PMID- 7780768 TI - A questionnaire to measure mother-to-infant attachment. AB - The Maternal Attachment Inventory (MAI) was developed and tested to provide a practical measure of maternal affectionate attachment. MAI items were identified from the literature, and their construct validity was assessed by experts who numerically rated them for relevance. The MAI, two other indicators of maternal attachment, and a measure of maternal adjustment were completed by 196 women approximately 1 month after the birth of their infants. Two subgroups of women completed the research instruments when their infants were 4 (Group A) or 8 (Group B) months old. The MAI demonstrated evidence of validity through significant correlations with other indicators of maternal attachment (the How I Feel About the Baby Now Scale and the Maternal Separation Anxiety Scale) at all time points and a correlation with maternal adjustment as measured by the Maternal Attitudes and Maternal Adjustment Scale. The MAI also demonstrated evidence of acceptable internal consistency reliability at all three time points. PMID- 7780769 TI - The Index of Readiness: development and psychometric analysis. AB - This article describes the development and initial psychometric evaluation of a measure of individual appraisal of readiness to initiate health behavior change. Items were developed from inductively generated data to index dimensions of individual appraisal of readiness. Quantification of Index of Readiness content validity was established through the ratings of 10 experts, following criteria established by Imle and Atwood (1988). The instrument was tested in successive steps with 146 individuals who were participating in an outpatient cardiac rehabilitation program, for reliability and validity, including internal consistency reliability, and three forms of validity assessment (content validity, criterion-related validity, and construct validity). The three subscales of Reevaluation of Lifestyle, Identification of Barriers, and Goal Commitment demonstrated internal consistency. Criterion-related and construct validity were substantiated. With refinement, this measure will provide a basis for nursing interventions designed to enhance individual motivation in relation to specific health behaviors. PMID- 7780770 TI - Development of the Multidimensional Hope Scale. AB - In this psychometric study, a scale to measure hope in chronically ill patients was developed and evaluated. Four hundred fifty participants with a variety of chronic diagnoses completed two forms of the Multidimensional Hope Scale (MHS) (state and trait) and the Beck Hopelessness Scale (BHS). High levels of internal consistency (alpha = .95) and test-retest reliability (r = .82, p < .001) were estimated for the state form. Good concurrent validity was also indicated with a significant negative correlation between the MHS and the BHS (r = -.45, p < .001). Factor analysis using principal axis factoring and oblimin rotation identified six factors: Resource to Others, Civic Interest, Spirituality, Health, Social Support, and Self-Actualization. The psychometric data suggest a promising tool for measuring hopefulness in physically ill individuals. PMID- 7780771 TI - The Maturation Index of Colostrum and Milk (MICAM): a measurement of breast milk maturation. AB - A biological marker, the Maturation Index of Colostrum and Milk (MICAM), was developed using filter paper chromatography. The MICAM consists of five patterns used to measure the individual rate of breast milk maturation among mothers. This article documents the biological basis of MICAM patterns as a gradual breakdown of an emulsion of breast milk that is dependent on the ratio of sterols plus phospholipids to fat content of the milk. Frequencies of MICAM patterns by day, timing of the milk collection, and inter-rater reliability are addressed and the construct validity is explored. This was a partial replication of the original tool development reported by Humenick in 1987. In both studies, the variables of timing of breast-feeding initiation, frequency, and cumulative length of breast feeding episodes were significantly correlated as predictors of early milk maturation as measured by the MICAM. Milk maturation rate was also significantly correlated as a predictor of infant weight gain, weeks of sustained breast feeding, and maternal-infant breast-feeding satisfaction. The MICAM can be used as a clinical screening tool to assess the progress of milk maturation in cases where breast-feeding has had a difficult or delayed initiation, and to evaluate interventions designed to support lactation. PMID- 7780772 TI - Ending batting slumps in baseball: a qualitative investigation. AB - This study used a qualitative method of inquiry to examine how baseball players cope with batting slumps. Players from one national junior (n = 30) and several semi-professional teams (n = 35) made up the sample. Through the use of an open ended question, each subject was asked to provide advice to players experiencing a batting slump. Inductive content analysis procedures were used to analyse the quotes from the open-ended question. Six major categories of coping strategies emerged from the data: focusing on the task, returning to basics, being actively positive, avoiding negativism, increasing effort, and seeking coaching. These findings contribute to the suggestion that baseball players use a variety of coping strategies to deal with batting slumps. Results also showed that national junior and semi-professional players differed on some of the coping strategies they considered to be most helpful. How this information can be used by coaches and sport psychologists is discussed. PMID- 7780773 TI - The efficacy of isokinetic, isometric and vertical jump tests in exercise science. AB - This research examined the efficacy of several tests of muscular strength and power in their capacity to be related to performance, their ability to effectively discriminate between individuals of different performance levels and their sensitivity in detecting training induced changes to performance. Thirty healthy active subjects performed the following maximal tests of muscular function: (1) Vertical jump; (2) Isokinetic knee extension at 1.05, 3.14 and 5.24 rads s-1; and (3) Isometric rate of force development. Performance was assessed by the peak power output achieved on a cycle test. In addition, subjects participated in a 10 week resistance training program. The isokinetic and vertical jump tests were significantly related to performance (r = 0.5-0.73) and could be used to discriminate between subjects of differing performance levels. However, the isometric rate of force development test was an ineffective assessment modality. None of the tests were able to effectively monitor training induced changes in performance, as evidenced by non-significant correlations between the pre- to post-percentage changes in cycling performance and the test variables. Consequently, alterations to training programs for athletes should be based on changes in actual performance, as opposed to muscular function tests. PMID- 7780774 TI - Gastrointestinal blood loss in triathletes: it's etiology and relationship to sports anaemia. AB - Twenty male triathletes (R 18-39 mean = 27.5 yrs) provided blood and faecal samples during intense training, pre-race taper and post-competition. All answered a closed-end questionnaire on intake of aspirin, NSAIDS, Vitamin C, iron and red meat. History of GIT blood loss and training distances were also obtained. Blood samples were taken on three occasions and analysed for Haemoglobin(Hb) and Serum Ferritin concentrations. Faecal specimens were collected on five occasions and assessed for blood loss using Haemoccult II and Monohaem (a monoclonal antibody test specific for human haemoglobin). Mean Hb and 95% confidence intervals at the three stages were 14.53gm/l (13.95-15.10), 14.9gm/l (14.46-15.34), 14.57gm/l (14.18-14.97) respectively. There was a small, but statistically significant, increase in Hb during the pre-race taper period (paired t = 2.65, p < 0.05), and a non-significant drop in Hb post-event (paired t = 1.89, p = 0.075). Mean ferritin, MCV and haematocrit values did not significantly change. Eighty percent of the group exhibited faecal blood loss on one or more of the tests used. There were significant increases in both Haemoccult (chi 2 = 5.44, p < 0.04) and Monohaem (chi 2 = 7.36 p < 0.02). Regression analysis demonstrated a significant relationship between training Hb and total training intensity (R = -0.61, F1,l5 = 8.98, p < 0.009) and training run intensity (R = -0.55, F1,l5 = 6.17, p < 0.026), as estimated using Coopers aerobic points system. These results confirm that GIT blood loss is common in endurance athletes, and appears to be related to exercise intensity. The possible mechanisms of blood loss are discussed. PMID- 7780775 TI - Biomechanical responses of elite swimmers to staleness and recovery. AB - Tethered swimming forces (TSF), average distance achieved per stroke (D/S) during a submaximal effort swim, and time and D/S for a maximal effort swim were measured to determine changes occurring with staleness and recovery. Fourteen nationally ranked male and female swimmers were studied five times (i.e. early-, mid-, and late-season, during tapering, and after competition). ANOVA and Newman Keuls post-hoc tests were used to assess changes during the season. Three swimmers were classified as stale and showed a deterioration (0.7%) in maximal performance time from early- to late-season which was significantly different (P < 0.05) from the improvement (3.1%) demonstrated by the non-stale swimmers. Daily self-ratings of fatigue, kept by the swimmers in log books during the season, were significantly higher (P < 0.001) for the stale compared with the non-stale swimmers. No significant differences were established between the stale and non stale swimmers in TSF or D/S during the season or in the response to tapering. A significant improvement (P < 0.05) in TSF was observed from before to after tapering. It was concluded that TSF and D/S may not change significantly with staleness and that the recovery period of tapering prior to competition allows swimmers to generate greater forces in the water. PMID- 7780776 TI - Victimization prevention programs: a national survey of children's exposure and reactions. AB - The National Youth Victimization Prevention Study interviewed a representative sample of 2,000 U.S. children and their caretakers about the children's experience with child abuse and victimization prevention programs. Two-thirds of the children reported being exposed to at least one program at some time, 37% within the last year. Programs that gave children a chance to practice, that prompted discussions with parents, and that included information on dealing with bullies were more likely to result in utilization of the program skills. Although satisfaction levels were generally high for all groups, girls, black children, and children from lower socioeconomic status families, as well as their parents, had more positive reactions and reported more skill utilization. Some children did report, and their parents confirmed, more worry about abuse and fear of adults. However, the children with increased worry and fear were also the children who themselves and their parents reported the most positive feelings about the programs and the most skill utilization. This suggests that the level of worry and fear induced by the programs was appropriate to the subject. PMID- 7780777 TI - The effectiveness of victimization prevention instruction: an evaluation of children's responses to actual threats and assaults. AB - This study examined whether instruction in school and at home about how to prevent victimization has any impact on children's behavior in situations of real victimization threat. Telephone interviews were conducted in 1992 with a nationally representative sample of 2,000 youths age 10 to 16 and their caretakers. More comprehensive school programs had mixed, small but overall positive effects. Children exposed to such school-based prevention programs performed better on a short test of knowledge about sexual victimization; when victimized or threatened were more likely to use the self-protection strategies recommended by prevention educators; were more likely to feel that they had been successful in protecting themselves; and were more likely to disclose to someone about the victimization attempts. They were not better able to limit the seriousness of the assaults and, in fact, they experienced more injuries in the course of sexual assaults. Comprehensive parental instruction also had positive effects on knowledge, the use of preferred self-protection strategies and the likelihood of disclosure. Children with comprehensive parental instruction were more likely to limit the seriousness of assaults. PMID- 7780778 TI - Emotional, behavioral, and physical symptoms reported by parents of sexually abused, nonabused, and allegedly abused prepubescent females. AB - There have been few studies that have examined emotional, behavioral, and physical symptoms that discriminate between well-defined groups of sexually abused and nonabused children. This study examined the results of a structured parent interview (SASA) completed on three matched samples of prepubescent females: 68 who were selected for nonabuse (NA Group), 68 from a sexual abuse clinic in which a perpetrator confessed (SA Group) and 68 seen at the same clinic who did not have a perpetrator confession (AA Group). Parents of girls in both the SA and AA groups reported increased sleep problems, fearfulness, emotional and behavioral changes, concentration problems, and sexual curiosity and knowledge. When contrasting the known (SA) with the allegedly abused sample (AA), self-consciousness, nightmares, and fearfulness of being left alone emerged significantly more frequently in the SA sample. PMID- 7780779 TI - Characteristics of childhood sexual abuse in a predominantly Mexican-American population. AB - Little has been written about the characteristics of childhood sexual abuse among Mexican Americans. In addition, certain aspects of the epidemiology of reported sexual abuse in the United States have changed significantly over the past 12 years. To better understand how characteristics of sexual abuse vary with ethnicity, race, gender, and age, we reviewed the records of 2,130 children under age 18 who were evaluated at our university-based facilities for possible sexual abuse from 1987 to 1989. The demographic, historical, and physical findings of the cases from our predominantly Mexican-American population were analyzed. T test, analysis of variance, and chi-square analyses were used to test for differences related to ethnicity, race, gender, and age. Significant differences in these factors were found with respect to the relationship of the perpetrator to the child, the number of perpetrators, the interval from the abuse to the evaluation, the types of abuse, and the findings of the physical examination. This study demonstrates the important influences of ethnicity, race, gender, and age on characteristics of childhood sexual abuse. Awareness of these influences can be helpful in understanding factors that contribute to childhood sexual abuse, preparing for legal proceedings, and designing appropriate prevention programs. PMID- 7780780 TI - Comparative psychopathology of women who experienced intra-familial versus extra familial sexual abuse. AB - The Diagnostic Inventory of Personality and Symptoms (DIPS) was used to assess psychopathology in a clinical sample of 30 women with histories of intra-familial sexual victimization, 22 women with histories of extra-familial sexual victimization, and 30 women with no victimization experiences. The present study examines whether the relative/nonrelative issue is significant to the impact of sexual victimization experiences. A clinical comparison of two point code types indicated that both sexually abused groups could be characterized as suffering an Affective Depressed-Dissociative Disorder. However, profile shapes produced for the intra- and extra-familial abused groups differed. A discriminant function developed via step wise selection procedures incorporated 12 of the 14 scales, correctly classifying 94% of the individuals (49 of 52) as members of the extra or intra-familial groups. Profile analyses, discriminant analyses, clinically descriptive comparisons, and post hoc analyses of individual scales all revealed that psychopathology is much more evident in those who have experienced sexual abuse. Methodological considerations are highlighted and implications for treatment and research are addressed. PMID- 7780782 TI - The maltreatment of intellectually handicapped children and adolescents. AB - Eleven and a half percent of intellectually handicapped children in Castilla-Leon are subjected to maltreatment; in these, physical neglect is the most frequent. These findings come from a questionnaire (CEMND) specifically designed to detect and discover the prevalence of maltreatment in a sample of 445 mentally retarded children. It was discovered that problems between the child's parents, the child's behavior and the interaction between both aspects were significant factors in situations of maltreatment. PMID- 7780781 TI - Risk factors for behavioral dysfunction: the relative impact of maltreatment, SES, physical health problems, cognitive ability, and quality of parent-child interaction. AB - An analysis to identify risks for behavioral dysfunction is described in which maltreatment is viewed as one of multiple factors putting behavioral outcome at risk. Based on a study of physically abused and neglected, and nonabused, non neglected children (n = 206) assessed at two points in time--preschool age and school age--variables representative of several domains (parenting, family environment, and child characteristics) were identified as significantly affecting children's behavioral functioning. Based on teachers' ratings, the children were assigned to one of three groups: high, medium, and low functioning. Discriminant analysis was used to determine which factors discriminated among the three groups. Results indicated that behavioral functioning is most strongly differentiated by the sociocultural and family climate in which the child is raised with physical and emotional maltreatment being significant but less powerful influences. PMID- 7780783 TI - Child abuse by the middle class? A study of professionals in India. AB - The purpose of this study was to determine if the abuse of children was prevalent among middle-class professionals in India. Face-to-face interviews were conducted with a stratified random sample of 319 subjects, in three cities in India, to assess their attitudes toward child rearing and their expectations about child development. These were then correlated with the methods of conflict resolution which had been used with children in the past year. Of the subjects who participated in the study, 56.9% reported having used "acceptable" violence, while 41.9% revealed that they had engaged in "abusive" violence. Interestingly, 2.9% admitted to having employed "extreme" violence toward their children. The correlations between parental attitudes and/or expectations and the use of different methods of conflict resolution did not occur as frequently as anticipated, suggesting that violence against children in India may well be the result of social sanction. Implications for intervention are suggested. PMID- 7780784 TI - The measurement of maltreatment: a comparison of approaches. AB - This study examined the comparability and predictive validity of three approaches to the measurement of child maltreatment. Adolescents (N = 160, aged 11-17) were randomly selected from the open caseload of a child protection agency. Global ratings of maltreatment severity were made by three reporting sources: researchers on the basis of protection agency case files, protection agency social workers, and the adolescents themselves. Ratings were made of five types of maltreatment: physical, sexual, emotional, neglect, and exposure to family violence. Self-reported (YSR) and caretaker-reported (CBCL) adjustment measures were also obtained for each subject. Results indicated that over 90% of the sample had experienced more than one type of maltreatment. Comparison of ratings across sources indicated considerable disagreement with respect to judgments of maltreatment occurrence and severity. Relative to professional ratings, adolescent ratings were better predictors of externalizing and internalizing symptomatology in both univariate and multivariate analyses. PMID- 7780785 TI - Judicial decision-making in contested custody cases: the influence of reported child abuse, spouse abuse, and parental substance abuse. AB - This study examined the relationship between allegations of maltreatment and substance abuse, and custody awards in Florida. Information concerning the presence, or absence, of these reports was collected on 60 contested initial disposition, or disposition modification cases, and was used to model judicial decision-making. Substantiated reports of child and spouse abuse occurred very infrequently in our sample. Conversely, substance abuse allegations occurred much more frequently. Judges appeared responsive to allegations of abuse with regard to awards of primary physical residence, despite the lack of substantiated evidence. Maltreatment allegations had no apparent impact, however, on awards of shared, versus sole, custody. Additionally, reports of parental substance abuse also had no apparent impact on judicial decision-making. Implications of these results are discussed. PMID- 7780786 TI - Child abuse prevalence in Russian urban population: a preliminary report. AB - Self-reported data from 375 early and mid-adolescent school children in a Siberian city estimated a prevalence of child abuse at 28.9%. Of these children, 3.8% suffered injuries that required medical attention. This prevalence of child abuse indicates the need for additional research and development of a system to identify and manage child abuse in Russia. PMID- 7780787 TI - Pediatric gonococcal infection: case report demonstrating diagnostic problems in remote populations. AB - The inability of Neisseria gonorrhoeae to survive prolonged transit times and hostile ambient temperatures has made its detection at referral laboratories by cultural methods untenable. In this situation, reliance upon antigen detection systems is attractive but when these tests are performed on vaginal specimens from children, false positive results are a significant concern. Some of the difficulties associated with the investigation of a gonococcal infection resulting from sexual abuse of a child in an isolated community are illustrated in this report. PMID- 7780788 TI - [Long term potentiation of the synaptic efficacy: mechanisms, functional properties and role in learning and memory]. AB - It is widely assumed that information is stored in the brain as changes in the efficacy of synaptic connections on those neurons which are activated during learning. In the past decade, long-term potentiation (LTP) of synaptic efficacy has become the dominant model in the search for the cellular bases of learning and memory. Today, considerable progress has been made in understanding the synaptic events underlying LTP and in identifying the neural systems which express LTP. In parallel, the hypothesis that the mechanisms underlying LTP are activated during learning and actually serve learning and memory has gained much empirical support. This article summarizes present knowledge about the properties and mechanisms of LTP and reviews the major experimental strategies that have been pursued to elucidate its functional significance in learning and memory. The data provide a working framework within which the dynamics of cellular mechanisms of learning and memory is profiled. PMID- 7780789 TI - [Hippocampus as interaction sites between cerebral memory systems]. AB - Most of the current theories assume that there are multiple forms of memory that are supported by separate brain systems and have different characteristics. Animals studies on the various dual-memory theories have been carried out mainly on the basis of hippocampal system function. Specifically, they have focused on aspects of learning and memory that are impaired (vs. spared) by lesions of the hippocampal formation. However, there are several instances in the animal literature showing that hippocampal lesions actually produced enhanced learning and memory function. Moreover, the acquisition of tasks that are facilitated by hippocampal lesions (or dysfunction) is nevertheless associated, in intact subjects, with specific neurobiological alterations in the hippocampus. This problem has been analysed using two different tasks in mice: a bar-press conditioning and a spatial discrimination task. Results showed that, depending on the task considered, the same pharmacological treatment produced either a facilitation or an impairment of acquisition. Moreover, each task induced significant alterations in hippocampal adenylate cyclase activity but in opposite directions. Together with previous findings, these results suggest that the hippocampus is involved in both the so-called "hippocampal-dependent" and "hippocampal-independent" forms of memory. It is postulated that some of the observed training-induced neurobiological alterations might reflect the interaction between two (or more) competing memory systems at the hippocampal level. Thus, in addition to its proposed specific information processing functions (i.e., relational), the hippocampus would play a role in addressing information to the brain memory system that, in a given situation, has the best adaptive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780791 TI - [From positional cloning to gene identification and its function in genetic diseases]. AB - The huge development of genetic tools, together with the availability of powerful computers have enabled the mapping of several loci responsible for genetic diseases by the positional cloning technique, also called reverse genetics. The step consisting of identifying the gene itself remains a difficult step and the function of the gene identified may remain difficult to establish. In this chapter, we will examine the various steps allowing the identification of the gene, techniques allowing the creation of animal models of human diseases and the recent progresses of these techniques. PMID- 7780790 TI - [Aging of memory mechanisms]. AB - Human amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7780792 TI - [Physical study of big fragments and search strategy of genes. Application to locus of infant spinal muscular atrophies]. AB - Spinal muscular atrophies (SMA) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood SMAs are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a YAC contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy-repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in 10 SMA patients. Moreover, deletions were strongly suggested in at least 18% of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of SMA. PMID- 7780793 TI - [Identification of mutation of RET proto-oncogene in Hirschsprung disease]. AB - Hirschsprung's disease is a frequent congenital malformation of the hindgut. The existence of Hirschsprung's families favors the role of an autosomal dominant gene with a reduced penetrance. We have successively localized and identified the RET proto-oncogene as the gene responsible for familial Hirschsprung's disease. Interestingly, other mutations of the RET proto-oncogene have been described in inherited predisposition to endocrine cancers. This observation shows that, depending on their nature, mutations of the RET proto-oncogene could lead either to early developmental defects or to tumor predisposition. PMID- 7780794 TI - [Cell adhesion and development of skeletal muscle]. AB - Cell adhesion is a cell autonomous property of pluricellular organisms at the basis of tissues and organs formation. Thus, adhesive processes must be considered as key features of the development of skeletal muscle as well as of other tissues. We present here the actual knowledge on cell adhesion molecules in skeletal muscle morphogenesis. The spatio-temporal expression patterns of N-CAM, N-cadherin, M-cadherin, VLA-4 and VCAM-1 during chicken and mouse myogenesis suggest that these cell adhesion molecules are differentially involved in myoblast-myoblast, myoblast-myotube and myotube-myotube interactions. These molecules link myogenic cells before they are separated by their basal laminae. They can potentially induce preferential cell adhesion and sorting-out as it has been described by Holtfreter. This differential adhesion may lead either to myoblast fusion or to preferential association between primary and secondary myotubes. PMID- 7780795 TI - [Analysis of the diversity of tropomyosin isoforms]. AB - Tropomyosins are a family of actin filament binding proteins. Like many structural proteins, tropomyosin isoform expression involves the use of multiple genes, but diversity is to a large extent generated by alternative processing of RNA. The tropomyosin family consists of 15 to 20 different protein isoforms which are coded by four genes. Each of these genes code for multiple proteins ranging from two up to as many as nine different isoforms. These genes have been named alpha CTM, alpha FTM, alpha STM and beta TM after to the striated muscle specific subunit of tropomyosin which they code. Their multiple coding potential is based upon the existence of multiple exons associated with initiation of transcription, multiple exons associated with polyadenylation signals and multiple mutually exclusive internal exons which are alternatively spliced. The regulation of this process of alternative splicing have been extensively studied both in the case of exons 2a/2b of the alpha FTM gene and in the case of exons 6a/6b of the beta TM gene. In both cases, one exon is specifically used in one type of muscle tissue, exon 2a is smooth muscle specific and exon 6b is skeletal muscle specific. In both cases, alternative splicing involves a combination of negative regulation, on exon 2b in smooth muscle and on exon 6b in non muscle tissues, and of competition in the alternative situation. PMID- 7780796 TI - [Serine proteases and their inhibitors: their role in the differentiation in neuromuscular system]. AB - It is now well established that some serine proteases, such as plasminogen activators and thrombin, as well as their inhibitors, have roles in the development of both central and peripheral nervous systems. We have shown that muscle plasminogen activators, activated after denervation, were able to digest some components of the muscle basement membrane. We have also shown that several inhibitors of serine proteases were concentrated at the neuromuscular junction. These are protease nexin, I, also called glia-derived nexin, protease nexin II, a secreted form of the beta-amyloid precursor protein (APP), and alpha 1 antichymotrypsine (ACT). These results leads us to propose a model in which serine proteases would favor plasticity of motor nerve endings during neuromuscular development. On the contrary, the inhibitors of serine proteases would act to provide and secure maintenance of the synaptic contact. A dysequilibrium between serine proteases and their inhibitors might underlie one or more motor neuron diseases. PMID- 7780797 TI - [Muscular reconstruction by myogenic cell graft]. AB - We have developed an experimental model to test the ability of cultured satellite cells to form new muscle fibers when grafted in an irreversibly injured muscle. Association of X-irradiation to autotransplantation reduced extensor digitorum longus muscles of adult rats to a cystic structure formed by a peripheral rim of surviving muscle fibers surrounding a central space devoid of myofibers. Grafting autologous satellite cells, multiplied and labelled in vitro, into this central space gave rise to new myotubes which developed and matured to form fully differentiated myofibers. Mecanophysiological recordings confirmed the improvement of functional parameters particularly a 4 fold increase of twitch and tetanic tensions in grafted muscles. Furthermore, we examined the role of old basal lamina in architectural organisation of the reconstituted muscle by electron microscopy and immunofluorescence using antibodies to laminin, fibronectin, type IV collagen and heparan sulfate proteoglycan. We observed the persistence of immunoreactivity to all components; anti-laminin antibodies for example, evidenced a clear fascicular organization of ghost basal lamina which are progressively repopulated by the grafted cells. We finally investigated in vivo proliferation of the grafted cells by an autoradiographic study of H3 thymidine incorporation in the regenerated fibers and demonstrate that grafted cells proliferate for, at least, 1 week after cell grafting. PMID- 7780798 TI - [Expression and localization of dystrophin during human skeletal, cardiac and smooth muscle development]. AB - Dystrophin, the Duchenne muscular Dystrophy gene product, is a large cytoskeletal protein associated with a complex of membrane proteins, the Dystrophin Glycoprotein Complex (DGC). Dystrophin is localized to the sarcolemmal membrane of all normal muscle types, but is absent from muscles of DMD patients. Using monoclonal antibodies raised against distinct regions of the dystrophin, we studied its expression and subcellular localization during human skeletal, cardiac and smooth muscle development. We have shown that the expression and the association of dystrophin with the plasma membrane take place earlier in cardiac and smooth muscles (8 weeks of gestation) than in skeletal muscles. In skeletal muscles, dystrophin is first observed in the cytoplasm, and is progressively localized to the plasma membrane from 10 weeks onwards. We obtained differences in staining when using antibodies against either the central part of the protein or the carboxy-terminal domain, and we suggested that isoforms of dystrophin, probably differing in their carboxy-terminal end and their capacity to associate with the plasma membrane were differentially expressed during development and in different tissue-types (7). These findings are discussed in the context of the pathology of Duchenne Muscular Dystrophy. PMID- 7780799 TI - [Main steps in the skeletal myogenesis in man]. AB - During the metabolic differentiation of developing human skeletal muscle fibers, two different generations of fibers can be characterised by their profiles of protein expression (in particular of the myosin heavy chains). This differentiation is regulated by both genetic and epigenetic factors (motor innervation, levels of thyroid hormone). The anomalies in different muscle pathologies can be better understood by comparison with the modifications occurring during normal skeletal muscle development. PMID- 7780800 TI - [Induction of prostatic buds in the absence of androgens]. AB - We have investigated the non-androgenic factors that induce the prostatic buds from the sinus epithelium. The buds were found to be induced in the explants cultured in the androgen-deficient medium containing 20 ng/ml rat keratinocyte growth factor (KGF) irrespective of the sex of the sinus. PMID- 7780801 TI - Transcription factors 1: bZIP proteins. PMID- 7780802 TI - [The geriatric team in ambulatory (mobile) rehabilitation. Results of a longitudinal study on the effects of ambulatory rehabilitation]. AB - This article describes the experiences obtained in a study of ambulatory (mobile) rehabilitation with stroke patients. The patients had been treated in a rehabilitation clinic before. The ambulatory rehabilitation, which lasted 18 months, served to maintain and further develop the previous success of in-patient rehabilitation. On the one hand, the research project provided empirical evidence for the success of ambulatory rehabilitation. On the other hand, the experiences obtained through this research project indicate that the success of an ambulatory rehabilitation concept is dependent on optimal co-operation among members of the rehabilitation team (physicians, psychologists, physical therapists, occupational therapists, speech therapists, and nursing staff). In relation, the institutional conditions for effective ambulatory rehabilitation are only met when physicians in private practice, who are responsible for the co-ordination of rehabilitation services, are supported by physicians in regard to time-consuming home visits, and when sufficient numbers of physical therapists, occupational therapists, and speech therapists in private practice are available. Unfortunately, these conditions are not fulfilled in many regions of Germany. PMID- 7780803 TI - [The geriatric team in the memory clinic]. AB - The early and differential diagnosis of senile dementia is still a problem. The work of a multiprofessional team in the Memory Clinic Essen is reviewed. the combination of qualifications of the team corresponds with the diagnostic algorithms of DMS-III R and ICD 10. Members of the team are a geriatrician, a psychiatrist, a geragoque, and a psychologist. Every specialist examines the patient using his specialized method. The results are discussed in a diagnostic conference. Out of the different methods and views of the specialists a comprehensive image of the patient takes shape and allows a better understanding of the dementia. PMID- 7780804 TI - [The geriatric team in transitional patient management]. AB - The transition team has its place in pre- and postdischarge nursing and therapeutic care, on the basis of a geriatric assessment. Core members of the team are, in the sequence of the scheduled performance in-hospital, nurse, occupational therapist, physiotherapist and social worker, supplemented by a team physician. Two-thirds of all treatments were in the hospital, one-third in an outpatient setting up to 4 weeks after discharge. Cooperation with outpatient services has been good. PMID- 7780805 TI - [The gerontopsychiatric team in the specialized department]. AB - People 65 years and older constitute a group with high risk for psychiatric disease, and their numbers are increasing. At the same time familial networks and financial resources are weakening. In order to improve psycho-geriatric therapy, we developed teamwork within our department. In the present work we describe the psycho-geriatric ward and the special functions of team members. It seems to be important that there are enough staff members who are well trained and motivated; it should be guaranteed that members regularly meet in conferences and have regular supervision; work hours should be favorable. Team process is described as consisting of imaging a comprehensive idea of the personality and the problems of the patient; agreeing on a therapeutic proceeding and-as a result-translating into action. Finally, it focuses on the necessity for further development and research. PMID- 7780806 TI - [Age differences versus aging--a cross-sectional and longitudinal analysis on the development of memory in advanced age]. AB - This study examines the development of episodic memory in later adulthood and old age in a combined cross-sectional and longitudinal design. 124 normal aging subjects, aged 50-87 years, representing four age groups (M1 = 53.65 years, M2 = 60.60 years, M3 = 68.44 years, M4 = 75.83 years) participated in a cross sectional study. Seven years later a retest was done in which 70% of the original sample again participated. Significant differences between the cross-sectional and the longitudinal results were found, with the latter showing the more severe decline in memory performances. Moreover, the age decline occurred earlier in the longitudinal study. Cohort differences account for these differences between the cross-sectional and longitudinal findings, favoring subjects of earlier-born cohorts. PMID- 7780807 TI - [The role of the medial services of health insurance in expert evaluation of disability in social insurance (SGB XI)]. PMID- 7780808 TI - [The geriatric team]. PMID- 7780810 TI - [The team of the geriatric day clinic]. AB - Composition of staff and therapeutic offers of day-hospitals principally are identical with those of geriatric hospitals. But there are peculiarities in their working: They offer a well balanced combination of somato-, physio-, psycho- and sociotherapy which individually must be planned, perpetually controlled and if necessary changed corresponding to the given situation of the particular patient. This so called therapeutic milieu is only to be preserved by a close cooperation and interchange of information within the team and an intensive motivation of the patient to cooperate with the therapists. PMID- 7780809 TI - [The geriatric university clinic]. AB - The very old are the fastest growing population group. Medical progress allows more autonomy and better quality of life for the elderly. Traditional medical concepts are, however, only partly suited for dealing with age-associated problems. Medical education responds to these new requirements in a limited way. Interdisciplinary teamwork is a prerequisite in treating the multimorbid, acutely ill elderly patient. The task of the university is not only the development and implementation of high-tech medicine, but first of all a comprehensive training in medicine, including geriatrics. The Geriatric University Clinic therefore offers pre- and postgraduate training in geriatrics, but also in related disciplines by promoting teaching and research. In order to attain these goals, the geriatric acute ward was created for acutely ill, very old, multimorbid, frail elderly patients. A geriatric ward for rehabilitation complements this ward. A consultation service offers geriatric know-how to all other services. A special task is the early diagnosis and treatment of dementia in an outpatient service. The aim is to prevent chronification by early intervention and to reestablish satisfactory function and autonomy. PMID- 7780811 TI - [The interdisciplinary team on the assessment unit]. AB - Comprehensive geriatric assessment is usually accomplished by multidisciplinary teams in order to meet the complexity of patients' needs. An implementation of information exchange, case reporting and planning of treatment in a systematic manner is a prerequisite for interdisciplinary team work. This report gives the results from a series of 54 patients consecutively admitted to an assessment unit. Assessment was predominantly accomplished by a core team (physician, nurse, social worker), and was supplemented by additional disciplines, if needed. The process of assessment and treatment resulted in functional improvement as assessed by an increase in the Barthel-Index score, 14 days after admission and at hospital discharge. More than 70% of patients surviving were discharged back to their homes. Geriatric assessment revealed a great need for additional ambulatory professional care although some patients used such health care services, already. PMID- 7780812 TI - [Surgical diagnosis of pancreatic diseases]. PMID- 7780813 TI - [Current status and prospectives of combating addiction of heroin]. PMID- 7780814 TI - [The role of tumor necrosis factor in acute pancreatitis and associated multiple organ failure]. AB - In 32 patients with acute pancreatitis (AEP = 15, ANP = 17), tumor necrosis factor (TNF) activity, oxygen-derived free radicals (OFR) and endotoxin contents were determined by L929 cell bioassay, Tetrabarbituric acid fluorometry and Limulus test respectively. The results showed that TNF and OFR elevated in patients with AP at the admission (P < 0.05 vs normal). The change of TNF and OFR responded to the clinical symptoms. TNF correlated to early multiple organ failure (MOF). In patients with late MOF, TNF and OFR were both the important factors. By measuring endotoxin, we found that endotoxemiae were not so important in early phase of the disease as in late phase, in which they made TNF and OFR released profusely. PMID- 7780815 TI - [Cryosurgery of acute hemorrhagic necrotizing pancreatitis]. AB - Acute hemorrhagic necrotizing pancreatitis (AHNP) was induced by introduct retrograde injection of the autologous bile in canine. The cryoprobe was under the influence of temperature ranging from -160C to -190C for fifteen to eighteen seconds, and the frozen areas were about 80% surface of pancreas. Cryotherapy of AHNP strongly inhibited the development of the inflammation in pancreatic parenchyma. Postcryotherapy 24hr for remarkably decreased the activities of pancreatic enzymes. The activities of phospholipase A, lipase and amylase in serum decreased by 502.1%, 355.8%, 502.5% respectively in 7 days. The level of blood glucose decreased. At the second week, the fibroblasts were growing around the residual pancreatic aciner cells and insular cells rich in intact zymogen granules. The mortality (6.89%) of the treatment group within 48 hours was significantly lower than that of the control group (100%). PMID- 7780816 TI - [The role of platelet activating factor in mesenterioangial microcirculatory disturbance complicated with acute pancreatitis in rats]. AB - To study shock in early acute pancreatitis (AP), we observed the change of mesenterio-angial microcirculation in the rat with AP induced by sodium taurocholate infused into the pancreatic duct. Meanwhile, the effect of platelet activating factor (PAF) receptor antagonist BN52021 upon the animal with AP was also investigated. 18 Sprague-Dawley rats were divided into three groups: pancreatitis group pan + BN52021 group and control group. pan + BN52021 group was injected BN52021 (10mg/kg) intravenously 5 minutes and 180 minutes after AP induction. The other groups were injected normal saline. We also studied the survival times of rats. The results showed slow mesenterio-angial small arteriolar and venular blood flow velocity and dilated meseaterio-angial small venular diameter during the early phase of AP. An protective effect of BN52021 on mesenterio-angial microcirculation injuries accompanied by AP was confirmed Animals treated with BN52021 survived 458.3 +/- 9.5 minutes whereas death occurred 243.3 +/- 2.3 minutes after AP induction in untreated rats (P < 0.01). PMID- 7780817 TI - [Application of transcranial color Doppler flow imaging in the carotid cavernous sinus fistulae]. AB - Transcranial color Doppler flow imaging (TCCDFI) allows for simultaneous two dimensional structural imaging and Doppler evaluation of blood flow through intact skull. With this technique, we evaluated 10 patients with carotid cavernous sinus fistulae (CCSF) and 35 normal volunteers. Each of them was confirmed by angiography. TCCDFI showed that patients with CCSF had typical signs in the affected part. The cavernous sinus had mosaic color shade. Pulse-Doppler showed disorderly polydirection vortex blood flow spectra in the mosaic color shade associated with murmur. Two-dimensional sonography and color Doppler imaging demonstrated a dilated superior ophthalmic vein (SOV) with arterialized blood flow. The Vmax of MCA and ACA in the affected side were lower than the healthy and normal side. The RI was lower than that of the healthy side and PCA of both sides was lower than that in normal volunteers. Two patients were examined after tubolization. Mosaic color shade disappeared and SOV returned to normal venous flow in patients completely occluded. Mosaic color shade reduced and SOV still aterialized blood flow in partly occluded patients. This technique helps to confirm the clinical diagnosis and to track the hemodynamics of CCSF patients and evaluate the effect of therapy. PMID- 7780818 TI - [Expression of c-myc, c-erbB-2, insulin-like growth factor II andepidermal growth factor receptor in hepatitis B, cirrhosis and hepatocellular carcinoma]. AB - In order to get a better understanding of expressions of multiple oncogenes and their possible roles in human hepatocarcinogenesis, 379 cases of liver tissues were investigated immunohistochemically. EGF receptors were immunolocalized mainly in the sinusoidal endothelial cells. They might not take part in the development of hepatocellular carcinoma (HCC), c-myc protein was showed to be expressed in cancer cells and the hepatocytes in the so-called "large-cell dysplasia" and in ductular metaplasia (DM). Its expression was also observed in some zone II hepatocytes of hepatic accini in 21% of normal liver tissues, which indicated that c-myc expression might also be related to the proliferation of mature hepatocytes. The positivity rate of c-erbB-2 product was shown to be highest among the oncogenic genes examined in this study. The positivity was observed in small polygonal liver cells (SPLCs) and the hepatocytes were observed in SCD and in DM. The expression level of c-erbB-2 oncogene in HCC cells was higher significantly than in normal hepatocytes, but lower than in SPLCs, the hepatocytes in SCD and in DM. We suggest that c-erbB-2 gene activation may play an important role not only in HCC genesis, but also in DM. Insulin-like growth factor II (IGF II), an oncofetal hepatocellular growth factor, was immunolocalized in the cancer cells, SPLCs and the hepatocytes in SCD, which indicated that activation and hyperexpression of IGF II gene might be responsible for the prominent proliferation of SPLCs and SCD, a crucial step in malignant transformation of hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780819 TI - [A light-microscopic and immunohistochemical study in testis tissue from hemorrhagic fever with renal syndrome autopsies]. AB - Testis tissues from 13 cases of hemorrhagic fever with renal syndrome (HFRS) were studied by light-microscopy and immunogold-silver staining (IGSS). Under routine light microscopy, the pathological lesions were found frequently in the spermatogenic epithelia, the basement membrane in the seminiferous tubules, and the mesenchyme around the tubules. Immunohistochemical studies showed that there were immune complexes (IgG) deposited mainly in the basement membrane in the tubules and interstitial cells, endothelial cells, and red cells of the small vessels around tubules mesenchyme. The injury mechanism is that the immuno complexes (IgG) are deposited in testis tissues from HFRS autopsies. PMID- 7780820 TI - [Apolipoprotein (a) phenotypes of patients with myocardial infarction]. AB - We studied apolipoprotein (a) (apo(a)) phenotypes of 69 myocardial infarction survivors and 56 stroke patients, and compared them with those of 190 healthy Chinese. The distribution of apo(a) phenotype frequency in cardio-cerebrovascular disease patients was different from those of controls. The frequency of the phenotypes B, S1 and S2 in patients was remarkably higher than that in controls within the same single-band apo(a) phenotype. Moreover, the Lp(a) serum concentrations in CCVD patients were significantly higher than those in controls within the same single-band apo(a) phenotype. PMID- 7780821 TI - [Interleukin-1 beta, interleukin-1 receptor antagonist mRNA expression of peripheral blood mononuclear cells (PBMC) in idiopathic nephrotic syndrome (INS) detected by biotin-labelled probe in situ hybridization]. AB - The pathogenesis of INS is related to the disorder of cellular immunity. Using the in situ hybridization of biotin-labeled probe and streptavidin -alkaline phosphatase conjugate detection system, we quantitatively analysed by true colour medical image analysis system the expression of IL-1 beta, IL-1ra mRNA of peripheral blood mononuclear cells (PBMC) from 4 cases of idiopathic nephrotic syndrome. IL-1 beta IL-1ra mRNA expression of PBMC in INS were significantly lower than those of the normal control (107.63 +/- 20.80 vs 195.56 +/- 31.14; 144.45 +/- 11.42 vs 370.38 +/- 100.48, respectively, P < 0.05). The expression of IL-1 beta mRNA was significantly lower than the IL-1ra mRNA expression of PBMC in INS (107.63 +/- 20.80 vs 144.45 +/- 11.42, P < 0.05). There existed dysregulation of IL-1 beta, IL-1ra mRNA expression in INS. The advantages of biotin-labelled probe in situ hybridization were also discussed. PMID- 7780822 TI - [3 retinoic acid isomers on proliferation and differentiation properties of APL cell line-NB4]. AB - We examined the effect of three RA isomers, including ATRA, 13C-RA and 9C-RA, on the proliferation and differentiation properties of NB4 cells, a cell line established from APL patient and carrying the typical translocation t (15;17). Standard parameters such as cell morphology, cell growth curve, dynamics of cell cycle, expression of clusters of differentiation and reduction of nitro blue tetrazolium (NBT) were used to evaluate the effects of the three isomers. During the first 48 hours of RA treatment, the APL cell maturation was coupled with the cell proliferation. Moreover, significant differences of differentiation-induced effect among RA isomers were observed. ATRA showed better results than 13C-RA while 9C-RA functioned even better than ATRA. These data are helpful to understand the mechanisms, by which RAs induce promyelocytic leukemia cell differentiation and open a new prospect for the clinical use of novel retinoic acid isomers. PMID- 7780823 TI - [Establishment of hybridoma lines and protective study of monoclonal antibodies against lipid A of endotoxins]. AB - For developing monoclonal antibodies (MAb) that bound to lipid A of the LPS molecule, we established several hybridomas cell lines by fusion of SP2/0 and spleen cells from BALB/c mice immunized by J5 mutant strain of E. coli 0111:B4. Each MAb exhibited a high titer by ELISA assay. Six of MAb were of immunoglobulin G isotype and another one immunoglobulin M. All of these MAb demonstrated different capacity to cross-react with several gram-negative bacteria and their endotoxins. Among them, 9G6 MAb improved the survival rate of mice significantly when administered 2 hours before the challenge by pseudomonas A and E. coli. These findings suggest that MAb will probably be useful in the treatment of sepsis caused by a wide variety of gram-negative bacteria. PMID- 7780824 TI - [Effect of NG-nitro-L-arginine methylester on the secretion of endothelin-1 in vivo and in cultured endothelial cells]. AB - We investigated the effect of nitric oxide, derived from L-arginine on the production of endothelin-1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and plasma endothelin-1 level of the femoral artery during hypoxic ventilation (FIO2 = 0.10) were 3.3 +/- 0.4kPa, 68.7 +/- 10.2kPa.s-1/L and 47.2 +/- 17.4ng/L respectively. NG-nitro-L arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of mPAP and PVR during hypoxic ventilation to 4.9 +/- 0.6 kPa and 160.9 +/- 34.6kPa. s/L and its effect lasted for 3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery was increased to 68.2 +/- 20.6, 72.8 +/- 20.9, 75.8 +/- 22.7 ng/L at 60, 120, 180 minutes respectively after the injection of L-NAME (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from human umbilical veins, endothelin-1 level of culture medium increased significantly in 10(-11) and 10(-7) mol/L L-NAME group (n = 9, P < 0.05 vs control group). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin-1 in vivo and in cultured vascular endothelial cells. PMID- 7780825 TI - [Effects of alveolar macrophage conditioned media from interstitial lung disease patients on the procollagen mRNA expression in human lung fibroblasts]. AB - We investigated the effects of alveolar macrophage (Am) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression in cells. 13 patients with ILD and 8 patients with bronchial carcinoma (BC) received bronchoalveolar lavage (BAL). The BAL fluid was collected and centrifuged to obtain cells of two groups. The cells were washed and incubated at 37 degrees C and 5% CO2 for 2 hours in DMEM with 10% FCS. Then the adherent Am was added with DMEM with 0.1% FCS. (2ml/10(6) cells), and cultured at 37 degrees C and 5% CO2 for 24 hours. The supernatant was obtained by centrifugation and stored in -20 degrees C for experiment. Lung fibroblasts were planted in 96 well microtitle plate and cultured to confluence. Each well was added 100 microliters Am conditioned medium and incubated for 16 hours, then added 5 uci 3H-TdR for measuring the fibroblast proliferation and incubated till 24 hours. The cells were collected and counted. The DMEM with 0.1% FCS was used as control. When stimulated with Am conditioned media from ILD patients, fibroblast proliferation increased 71%, but for media from BC patients, it just increased 14% (P < 0.05). After stimulated with conditioned media for 24 hours, the cells were trypzied, collected, ashed and isolated total RNA with guanine method. Several samples' total RNA was subjected to electrophoresis in 1% agaroseformaldehyde gel to test specificity of procollagen al (I) and al (III) cDNA probes. 10 micrograms total RNA of each sample was bloted to nitrit membrane and baked at 80 degrees C for 2 hours. PMID- 7780826 TI - [Progress in the exogenous pulmonary surfactant replacement therapy for the adult respiratory distress syndrome]. PMID- 7780827 TI - The structure and the mechanism of action of pyruvate carboxylase. AB - Pyruvate carboxylase plays an important role in intermediary metabolism, catalysing the formation of oxaloacetate from pyruvate and HCO3-, with concomitant ATP cleavage. It thus provides oxaloacetate for gluconeogenesis and replenishing tricarboxylic acid cycle intermediates for fatty acid, amino acid and neurotransmitter synthesis. The enzyme is highly conserved and is found in a great variety of organisms including fungi, bacteria and plants as well as higher organisms. It is a member of a group of biotin-dependent enzymes and the biotin prosthetic group is covalently bound to the polypeptide chain of the enzyme, there normally being four such chains in the native, tetrameric enzyme. The overall reaction catalysed by pyruvate carboxylase involves two partial reactions that occur at spatially separate subsites within the active site, with the covalently bound biotin acting as a mobile carboxyl group carrier. In the first partial reaction, biotin is carboxylated using ATP and HCO3- as substrates whilst in the second partial reaction, the carboxyl group from carboxybiotin is transferred to pyruvate. The chemical mechanisms of the partial reactions and some of the roles played by amino acid residues of the enzyme in catalysing the reaction have been elucidated. The domain structure of the yeast enzyme has been deduced by comparing its amino acid sequence with those of enzymes that have similar catalytic functions. The quaternary structures of the pyruvate carboxylases studied so far, all involve a tetrahedron-like arrangement of the subunits. The major regulator of enzyme activity, acetyl CoA, stimulates the cleavage of ATP in the first partial reaction and in addition it has been shown to induce a conformational change in the tetrameric structure of the enzyme. In the past, the lack of any detailed structural information on the enzyme has hampered efforts to fully understand how this and other biotin-dependent enzymes function and are regulated. With the recent cloning of the enzyme from a variety of sources and the performance of three-dimensional structural studies, the next few years should see much progress in our understanding the mechanism of action of this enzyme. PMID- 7780828 TI - The effect of lipid peroxidation on the activity of various membrane-bound ATPases in rat kidney. AB - Peroxidation of membrane phospholipids is accompanied by alteration of the structural and functional characteristics of membranes. Lipid peroxidation changes the activities of various enzymes. The present study evaluates the effect of lipid peroxidation on the activity of various ATPases localized on kidney membranes. Our experiments were performed on crude preparation of rat kidney membranes which were exposed to Fe2+.ADP/NADPH-induced lipid peroxidation. The extent of peroxidation was estimated by measuring the thiobarbituric acid reactive substances. Simultaneously the activities of different ATPases were determined and divided according to their ouabain sensitivity and Mg2+ dependency. We found that 10 min incubation of isolated rat kidney membranes at 37 degrees C with inductors of lipid peroxidation increased the production of thiobarbituric acid-reactive substances from 1.10 +/- 0.26 to 7.72 +/- 2.55 nmol malondialdehyde/mg prot. (+/- SD, n = 4). Under these conditions total ATPase activity was decreased from 681 +/- 77 to 507 +/- 82, ouabain-sensitive Mg(2+) dependent ATPase (Na+,K(+)-ATPase) activity from 249 +/- 54 to 81 +/- 21 and ouabain-insensitive Mg(2+)-dependent activity from 287 +/- 48 to 173 +/- 58 whereas apparently Mg(2+)-independent ATPase activity was increased from 145 +/- 37 to 253 +/- 42 nmoles P/min/mg prot. (+/- SD, n = 4). The study indicates different mechanisms by which lipoperoxides affect the function of membrane-bound ATPases activities. It is concluded that the ATPases activities are changed during lipid peroxide formation. PMID- 7780829 TI - Changes in apoprotein distribution between lipoprotein classes of hypercholesterolemic rats treated with ascorbate. AB - It is known that ascorbate has a lipid lowering effect, accompanied by a drop of apo B, in rats fed a diet enriched with 1.5% of cholesterol (Nath diet). In order to better clarify the role exerted by ascorbate in lipid metabolism, the effect of ascorbate administration on apolipoprotein pattern in rats fed the Nath diet was investigated. Wistar male rats fed for two months the Nath diet were treated i.p. with 60 mg/kg of body weight of ascorbate for 10 days. Blood collection before and after the treatment was performed by intracardiac puncture. Lipoproteins were prepared by preparative ultracentrifugation and their apoprotein content was obtained by densitometric scanning of the apoprotein electhrophoretic pattern. The decrease of total plasma cholesterol and triglycerides and of cholesterol, triglycerides and protein content of all plasma lipoproteins observed in ascorbate treated rats, is accompanied by a marked modification of the apolipoprotein pattern of all lipoprotein classes studied, with an increase of apo E content in VLDL-IDL and LDL fractions (135 and 44% respectively), and a decrease of C (37%), AI (70%) and B (37.5%) apoproteins in VLDL-IDL and of apo C (36%) in LDL. On the contrary, in HDL fraction ascorbate induces an increase of C apoproteins (26%) and a decrease of E and B apoproteins (47% and 71% respectively). The data reported clearly show that in hypercholesterolemic rats the lipid lowering effect of ascorbate administration, is accompanied by a marked modification of the apoprotein pattern of all lipoprotein classes studied. PMID- 7780830 TI - Heat stress stimulates high affinity GTPase in cervical carcinoma cells. AB - A primary cellular site involved in heat shock response of eukaryotic cells is located in plasma membranes. The mechanism by which heat shock is sensed and the signals that trigger heat shock response remain an enigma. We aim to determine the role of guanine-nucleotide binding proteins (G)-proteins in mediating heat shock response in eukaryotic cells. The effect of heat shock on high affinity GTPase activity in presence or absence of modulators of G-proteins, such as pertussis toxin was studied by measuring GTPase catalyzed release of 32[Pi] from gamma-32[P]GTP. The effect of pertussis toxin on induction of heat shock proteins in cells subjected to thermal stress was studied by SDS-PAGE analysis of 35[S] methionine labelled cellular proteins. Exposure of cultured human malignant cells to thermal stress (43 degrees C) resulted in a significant increase in activity of high affinity GTPase in the membranes (P < 0.001). This response to heat shock was inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin, suggesting the involvement of G-proteins in mediating heat shock response. To characterize this G-protein dependence further, we assayed thermal stress stimulated high affinity GTPase activity in cells pretreated with antisera (AS/7) raised against a synthetic peptide corresponding to the last 10 amino acids of alpha-subunit of inhibitory G-protein (Gi). A partial reduction in heat shock induced stimulation of GTPase activity was observed in the presence of this antisera. The pertussis toxin treated cells did not show induction of heat shock proteins in response to thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780831 TI - Alteration of glutathione, glutathione S-transferase and lipid peroxidation in mouse skin and extracutaneous tissues after topical application of gasoline. AB - The skin is the major environmental interface of the human body and is repeatedly exposed to a broad array of exogenous chemicals potentially capable of causing toxicity. In the present study we have applied 3, 6 or 12 ml leaded gasoline/kg body weight to the skin of adult male Swiss mice for 7 consecutive days and then sacrificed the animals on 8th day after an overnight fast. Glutathione (GSH) concentration, lipid peroxidation and other GSH-dependent enzyme activities were measured in skin, liver, brain and blood tissues of the mice. Topical application of 12 ml/kg gasoline caused a significant increase in water consumption by the animals, although, their body weight and food consumption was not significantly affected. A 40-60% decrease in blood concentration of glucose, triglyceride, and cholesterol was also observed after the treatment. The hemoglobin concentration, GSH content, lipid peroxidation and glucose 6-phosphate dehydrogenase activity of erythrocytes were not significantly affected by the gasoline treatment. However, a decrease in GSH concentration (16-21%), lipid peroxidation (30-60%) and glutathione S-transferase (GST) activity (30-40%) was observed in skin, liver and brain after gasoline application. Western blot analysis of tissues using antibodies against GST isoenzymes demonstrated an alteration in the expression of various GST isoenzymes after gasoline treatment. Our results suggest that topical exposure of gasoline causes some deleterious effects on skin and extracutaneous tissues. PMID- 7780832 TI - Induction of cytochrome P-450 isoenzymes in cultured monkey hepatocytes. AB - The effect of phenobarbital (PB), beta-naphthoflavone (beta-NF) and rifampicin (Rif) on the drug-metabolizing activity of cultured squirrel monkey hepatocytes was examined. The drug metabolizing activity (e.g. alkoxycoumarin dealkylase or steroid hydroxylase) gradually decreased during the culture period with 40-70% activity remaining at 72 hr. When 0.5 mM PB was added to the culture, the activities of 7-methoxycoumarin O-demethylase (MCOD) and 7-ethoxycoumarin O deethylase (ECOD) increased to 6-7 fold higher level than those of control at 72 hr. Testosterone 6 beta-hydroxylase (6 beta-OH-T) and testosterone 16 beta hydroxylase (16 beta-OH-T) activities were approx. 3-fold higher than those of the control. Addition of beta-NF significantly increased the activities of 7 ethoxyresorufin O-deethylase (EROD) and ECOD. Though statistically insignificant, Rif slightly increased 6 beta-OH-T activity. Western blot analysis indicated PB induced production of the CYP 2B and 3A subfamilies, while beta-NF and Rif induced that of the CYP 1A and the CYP 3A subfamily, respectively. PMID- 7780834 TI - Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. AB - Since the type of fat consumed in the diet may play a role in the development of several disorders, it is important to ascertain the effects of different dietary fats upon parameters such as serum lipid levels and adipose deposition. The aim of this study was to determine the effects of feeding rats a range of fats with differing fatty acid compositions. Weanling male rats were fed for 10 weeks on a low fat (LF) diet or on one of five high fat diets, which contained 20% by weight of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Food intake, animal growth, tissue weights at sacrifice, serum and liver lipid concentrations and serum, heart, brain and adipose tissue fatty acid compositions were studied. The food intake of the LF-fed animals was greater than that of animals fed on the high fat diets; there were no differences in food intake between animals fed the high fat diets. The total energy intake was lower for animals fed on the HCO diet than for those fed on the LF, OO, EPO or MO diets; there were no other differences in energy intake between the groups. Animals fed the different diets had almost identical rates of weight gain up to 5 weeks; after this period of rapid growth, the increase in weight was slower in all groups but especially in the LF-fed animals. The LF-fed rats had a lower total weight gain and smaller final weights than rats fed on the high fat diets. Animals fed on the MO diet had a greater weight gain than those fed on the OO or EPO diets and their final weights were greater. The MO diet resulted in greatly increased liver weight compared with each of the other diets. The HCO, OO and EPO diets also increased liver weight compared with the LF diet. The total lipid content of the livers from rats fed the high fat diets was greater than that of those from rats fed the LF diet; the livers from animals fed the MO diet contained more lipid than those from animals fed each of the other diets. MO feeding increased the free cholesterol, cholesterol ester and triacylglycerol contents of the liver.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7780833 TI - Arginine and ornithine metabolizing enzymes in testosterone-induced hypertrophic mouse kidney. AB - Administration of testosterone to female mice causes hypertrophy of their kidneys with spectacular induction of ornithine decarboxylase and significant increase in the level of putrescine. We tried to find out whether testosterone treatment affects also the renal activities of enzymes participating in the formation and utilization of ornithine, specifically arginase and ornithine aminotransferase, and whether they are dependent on putrescine level. Swiss, CFW, DBA2 or F1 (CFW x DBA2) female and male mice were injected with testosterone (125 mg/kg) or CB 3717 (100 mg/kg). DFMO was applied in the drinking water. The activities of the enzymes were determined 24 hr or 5 days after administration of CB 3717 or testosterone, respectively. Renal activities of ornithine decarboxylase (ODC), arginase and ornithine aminotransferase (OAT) were found to be sex differentiated. The highest activity of ODC was characteristic for the kidneys of males, whereas those of arginase and OAT for the kidneys of females. In the kidneys of testosterone-treated female mice a decrease (50%) of OAT, and a significant increase of arginase activities (up to 200%), were observed. In the males these changes were less pronounced. DFMO, which completely inhibited the activity of renal ODC, did not influence significantly the testosterone-induced arginase and the testosterone-decreased OAT. Arginase and OAT, in contrast to ODC, were not changed in CB 3717-induced hyperplastic kidney. The study showed testosterone-induced differential changes in the activity of two enzymes involved in ornithine biosynthesis and catabolism which accompanied ODC induction in female mouse kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780835 TI - Factors affecting the stability of the renal sodium/phosphate symporter during its solubilization and reconstitution. AB - Phosphate is reabsorbed across the brush-border membrane of the proximal tubule by a specific sodium-dependent symporter. Like the other brush-border membrane transport proteins of the kidney, the phosphate carrier remains to be isolated in a functional state. To establish a set of parameters that allow to preserve its biological activity, the phosphate carrier was solubilized under systematically varied conditions and reconstituted into proteoliposomes. Successful reconstitution was achieved only when the extraction buffer contained lipids extracted from the renal brush-border membrane. Glycerol, an osmolyte which reduces the water activity of the solution, was also required. It could however be replaced by 150 mM sodium or potassium phosphate. Below this concentration and in the presence of glycerol, the ionic strength of the solution had little effect on the stability of the transporter, but sodium phosphate could not be replaced by sodium chloride. Phosphate transport in reconstituted vesicles depended on the concentration of detergent and pH of the extraction buffer. Finally, transport activity was increased when solubilization was carried out in the presence of a reducing agent, dithiothreitol. These results should be helpful during the purification and further characterization of the renal phosphate symporter. PMID- 7780836 TI - Presence of Vicia graminea lectin- or Vicia unijuga lectin-binding (Vgu) glycoproteins, Vgu glycoproteins with Thomsen-Friedenreich (T) activity and T active glycoproteins in human meconium. AB - Perchloric acid-soluble fraction prepared from a mixture of meconiums of 22 newborn babies was subjected to a systematic affinity chromatography using Vicia unijuga lectin-Cellulofine column and Arachis hypogaea lectin-Agarose column and separated into four fractions, Vgu glycoprotein, Vgu glycoprotein with T activity, T-active glycoprotein and another glycoprotein fractions. HPLC analysis showed that the first fraction contained three glycoproteins with molecular weight (Mw) of about 19,400 kDa, 5500 kDa and 1900 kDa, the second fraction consisted of two glycoproteins with Mw of about 460 kDa and 150 kDa and the third fraction composed of several glycoproteins including the main glycoprotein with Mw of about 11,700 kDa. PMID- 7780837 TI - Nursing challenges in the care of very low birth weight infants (< 1,000 grams). AB - It is not unusual for neonates to be born before the 24th week of gestation and weigh less than 1,000 g. These neonates are surviving to be transferred to a tertiary care center, and many are discharged eventually to home. When one considers that these infants are only "half developed" by the standard 40-week gestational period, it is understandable that the challenges for nurses caring for them are enormous. In this article, the authors review gestational development and the critical care needs of this special neonatal population. PMID- 7780838 TI - Consequences of perinatal asphyxia. AB - Perinatal asphyxia occurs in 3-9 of every 1,000 births. The risk for perinatal asphyxia is present in every pregnancy. When asphyxia is diagnosed in a newborn, the effects on the infant are potentially life-threatening. Management of the asphyxia focuses on initial stabilization and support based on identified organ system dysfunction as well as support for the infant's family. Long-term outcome for the asphyxiated infant is related to the degree, duration, and resolution of organ system dysfunction. PMID- 7780839 TI - Liquid ventilation: it's not science fiction anymore. AB - Liquid ventilation is, by all initial considerations, an unconventional concept. Decades of research, however, have found that by using perfluorocarbons, which are capable of holding high concentrations of critical gases such as oxygen and carbon dioxide, gas exchange optimal enough to support life is possible with no known toxic effects. The earliest method of liquid ventilation, tidal liquid breathing, involved infusion and active removal of tidal volumes of perfluorocarbons by a liquid ventilator for gas exchange. Recently, a new method of partial liquid breathing, called perfluorocarbon-associated gas exchange, makes the process of liquid ventilation simpler by using conventional gas ventilators. Current research is showing great promise in the use of liquid ventilation for patients with pulmonary pathology. Critical care nurses should become knowledgeable of this new mode of ventilation and be prepared to meet the special needs of this unique population. PMID- 7780840 TI - Perioperative management of pulmonary circulation in children with congenital cardiac defects. AB - Congenital cardiac defects and the clinical symptoms they exhibit are affected intimately by the relation they have with pulmonary circulation. Cardiac lesions that increase pulmonary blood flow often occur clinically with signs and symptoms of congestive heart failure, including hepatomegaly, tachycardia, diaphoresis, and feeding difficulties. However, in the neonatal period, pulmonary vascular resistance often remains elevated, decreasing the pulmonary blood flow and, therefore, severity of symptoms. Cardiac lesions that reduce pulmonary blood flow often manifest early in life with clinical signs and symptoms of cyanosis, tachypnea, and acidosis. Finally, cardiac lesions that result in isolated pulmonary blood flow manifest immediately in the neonatal period, with profound cyanosis and acidosis. In all three groups of cardiac anomalies, critical care nurses play a key role in the control of pulmonary vascular resistance and blood flow by collaborating in therapies designed to increase, decrease, or promote mixing to reduce morbidity and mortality. PMID- 7780841 TI - Current controversies in pediatric transplantation. AB - Transplantation in children has become a therapeutic option for several end stage organ diseases. The kidney, liver, and heart are the most common organs' transplanted; however, an increasing number of children are undergoing successful intestine, lung, and multiple organ transplant combinations. Through case study reports, emerging transplant options for the child experiencing end stage liver, intestine, heart, and lung failure are described. Critical care nurses play a crucial role in the postoperative recovery of these patients. An understanding of the transplant process and consequences of immunosuppression will help the critical care nurse identify signs of rejection, infection, and posttransplant lymphoproliferative disease. PMID- 7780842 TI - Meningococcemia: recognizing and reducing complications in pediatric patients. AB - Meningococcemia is a true infectious emergency that requires tremendous skill and collaboration among health-care professionals to reduce the high morbidity and mortality associated with this disease. Complications and sequelae may effect virtually every body system with meningococcal disease. The critical care nurse plays a crucial role in preventing and recognizing complications to reduce serious consequences, including respiratory distress syndrome, myocarditis, cardiovascular collapse, coagulopathies, major skin loss, and limb amputations. PMID- 7780843 TI - Visitation in the pediatric intensive care unit: controversy and compromise. AB - Much controversy has arisen in the last few decades regarding parental and family visitation in the intensive care setting. The greatest needs of parents while their child is in an intensive care unit include: to be near their child, to receive honest information, and to believe their child is receiving the best care possible. The barriers that exist to the implementation of open visitation mostly are staff attitudes and misconceptions of parental needs. Open visitation has been found in some studies to make the health-care providers' job easier, decrease parental anxiety, and increase a child's cooperativeness with procedures. To provide family-centered care in the pediatric intensive care unit, the family must be involved in their child's care from the day of admission. As health-care providers, the goal is to empower the family to be able to advocate and care for their child throughout and beyond the life crisis of a pediatric intensive care unit admission. PMID- 7780844 TI - AACN--SCCM Health Care Ethics Forum '94. Arlington, Virginia, March 1994. Proceedings. PMID- 7780845 TI - HealthCare Ethics Forum '94: health-care reform and clinical ethics: old values for new times. PMID- 7780846 TI - HealthCare Ethics Forum '94: ethical care from the patient's perspective. PMID- 7780847 TI - HealthCare Ethics Forum '94: ethics committees: living up to your potential. PMID- 7780848 TI - HealthCare Ethics Forum '94: organ transplantation and donation. PMID- 7780849 TI - HealthCare Ethics Forum '94: ethical challenges in the critically ill: use of restraints. PMID- 7780850 TI - HealthCare Ethics Forum '94: euthanasia and assisted suicide: critical care perspectives. PMID- 7780852 TI - HealthCare Ethics Forum '94: caregiver distress: if it is so ethical, why does it feel so bad? PMID- 7780851 TI - HealthCare Ethics Forum '94: advance directives: the critical challenges. PMID- 7780853 TI - HealthCare Ethics Forum '94: perspectives on withholding and withdrawal of life support. PMID- 7780854 TI - HealthCare Ethics Forum '94: pain management and sedation in the terminally ill. PMID- 7780855 TI - HealthCare Ethics Forum '94: medical futility: a bedside perspective. PMID- 7780856 TI - The midlevel practitioner role: one medical center's experience. AB - Numerous trends in the current health-care environment have converged to produce an increased emphasis on the role of the midlevel practitioner. Financial constraints head the list, including a mandate for the best care at the lowest rates and a resulting shift from costly specialists to primary care providers. The desire to conserve human and technologic resources requires a practitioner with advanced knowledge and skills to serve as gatekeeper in terms of facilitating access to health care, establishing efficient referral patterns, and developing a holistic care plan. The midlevel practitioner also is prepared to facilitate the transition from the intensive care unit to the less costly general care areas. In addition, the inevitable reduction in funds for graduate medical education and the dwindling number of first-year medical students choosing internal medicine as a specialty threaten the ability of academic medical centers in particular to provide adequate housestaff coverage to full-time and voluntary faculty members. Physicians eager to provide efficient, seamless care to patients in the acute care setting, while maintaining an office practice and caseloads at several hospitals, find the support provided by a midlevel practitioner an enhancement to their clinical practice and a solution to the continuous management of acute and chronically ill patients. In this article, the authors describe one medical center's experience in implementing the midlevel practitioner role. PMID- 7780857 TI - Implementation of the acute care nurse practitioner role. AB - In this article, the experiences of two new acute care nurse practitioners working at the University of Pittsburgh Medical Center are described. Included are the experiences they encountered in initiating the role and some of the responsibilities they assumed. PMID- 7780858 TI - No-effect level of subacute tetraethoxysilane inhalation on the mouse kidney. AB - To determine safe exposure levels of tetraethoxysilane (TEOS) in the kidney, groups of male ICR mice (SPF grade) containing 10 animals each were exposed to TEOS, 100 ppm or 50 ppm, for 6 hours/day, 5 days/week, for 2 or 4 weeks. Tubulo interstitial nephritis developed in mice exposed to 100 ppm for 2 and 4 weeks, but no kidney lesions or renal function changes were observed in mice exposed to 50 ppm. However, histopathological changes were detected in the nasal mucosa of mice exposed to 50 ppm TEOS. These results indicate that the occupational exposure level for TEOS should be strictly maintained below the current recommended exposure limit, 10 ppm, set by many countries and academic associations, and that renal tubular function of TEOS-exposed workers should be assessed and monitored for a long period. PMID- 7780859 TI - Influence of different doses of methyl ethyl ketone on 2,5-hexanedione concentrations in the sciatic nerve, serum, and urine of rats. AB - Rats were injected subcutaneously with 2,5-hexanedione (2,5-HD 2.6 m mol/kg) alone (HD group) or with 2,5-HD and methyl ethyl ketone (MEK) (2.6 m mol/kg of each agent, HD&MEK group) or with 2,5-HD 2.6 m mol/kg and 5 times that dose (13.0 m mol/kg) of MEK (HD&5MEK group). The concentration of 2,5-HD in serum and in the sciatic nerve was determined 0.5, 1, 2, 4, 8, and 16 h after administration. Urinary 2,5-HD concentration was determined from the beginning of administration up to 16 h afterward. 1) The concentration of 2,5-HD in the serum, the sciatic nerve, and the urine was increased significantly (p < 0.05) in the co administered groups; the higher the MEK doses were, the greater was the increase. 2) The clearance of 2,5-HD from both the serum and the sciatic nerve was delayed in the co-administered groups. The highest concentration in serum and the sciatic nerve appeared at 1 and 2 h respectively. After administration, the biological halflife (t1/2) of 2,5-HD from 1 to 8 h in serum was 6.5, 5.8 and 12.0 h for the HD, HD&MEK, and HD&5 MEK groups respectively. From 8 to 16 h, the t1/2 in serum was 1.2, 3.2 and 16.6 h for the HD, HD&MEK, and HD&5MEK groups, respectively. In nerve tissue, the prolongation of clearance in the co-administered groups was greater than that in serum, the t1/2 from 2 to 8 h being 5.2, 9.6 and 19.9 h for the HD, HD&MEK, and HD&5MEK groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7780861 TI - [The study of the relation between the working conditions and the prevalences of obesity, liver disorder and hyperlipidemia: evaluation of physiological examination data during the terms of car manufacturing work and car sales work]. AB - To evaluate the relation between the working conditions and the workers' health, particularly the prevalences of obesity, liver disorder and hyperlipidemia, we analyzed physiological examination data and the questionnaire survey about life behaviors and working conditions during the terms of car manufacturing work and car sales work among 61 male subjects. In the physiological examination data, compared with the term of car manufacturing work, the values of body weight, body mass index (BMI), GOT, GPT, gamma-GTP, TG and T-CHO elevated and the prevalences of obesity and liver disorder increased during the term of car sales work. During the term of car sales work, the prevalences of alcohol drinkers and cigarette smokers increased and the changes of food intake behaviors were noted. It was estimated that the changes of food intake behaviors associated with the differences of working conditions contributed increasing number of obesity and liver disorder that was based on fatty liver caused by hyperlipidemia. These results of this study suggested that working conditions associated with the prevalences of obesity, liver disorder and hyperlipidemia were important to conduct the effective health education in the present occupational health administration. PMID- 7780860 TI - [Effectiveness of continuous good dental health cares contributing to 20 teeth retained]. AB - This study was made to demonstrate what kinds of continuous care for dental health have teeth remained even at the elderly time. Questionnaires were mailed to 632 men retired from a company at the age of 60s or more, September-October in 1992. Of 424 cases recovered (67.1%), 414 (97.6%) i.e., 185 cases at the age of 60s, 172 of 70s, and 57 of over 80s, were subjected to analysis. All the subjects were classified into two groups. One is the group who has 20 teeth or more, the other having 19 teeth or less. Furthermore, each group was classified into three groups. The first group was no dental health care [DHC] group (group 1), the second one was starting DHC at the age of 20s or 30s (group 2), the third one was doing at the age of 40s or 50s (group 3). These groups were compared with each other group. Items related to dental health were developed by ourselves. Chi square test was done to prove the relationship between the starting time of continuous DHC and retention teeth of 20 teeth or more in the three age groups. The following three items related to dental health care may contribute significantly to retention teeth of 20 teeth or more at each age group, 1) changing to new brush every 2 or 3 months (p < 0.01), 2) making an effort to have hard foods (p < 0.01), 3) having calcium-rich foods (p < 0.05). PMID- 7780862 TI - [The effect of fixed night work on blood pressure of male bakery workers in a processing plant]. AB - The effect of fixed night work on blood pressure was investigated for the 13 male bakery workers. All were on the fixed night duty for the first 5 years. The mean BP values of the subjects began to rise significantly from the 4th year. At the 6th year, half of the subjects switched to working in shifts. After that, no increase in the mean BP values was seen in this group. Further increase in the values was observed in the other group on the night duty. However, a two-hour nap late at night prevented the rise of the mean BP values. PMID- 7780863 TI - Effect of pyrethroid (allethrin and fenvalerate) on excitability changes following nerve impulse. AB - Pyrethroid insecticides induce two different clinical symptoms. The difference has been reported to depend on the effect on the sodium channel opening time. We performed the present study to confirm this report by a double stimulation method. Allethrin (type I) 5 mg/kg and fenvalerate (type II) 1.5 kg/mg were injected into pentobarbital anesthetized rats. Tail nerve excitability was examined by a double stimulation method at from 4 msec to 40 msec intervals. The excitability was expressed as a percentage of the response to conditioned stimuli following supernormal stimuli to response to unconditioned stimuli. In control rats, the largest excitability was 94.6 +/- 19.2% at an 8 msec stimulus interval. After allethrin injection, we obtained two types of excitability changes. In some rats, supernormal excitability was present from 4 msec to 15 msec up to 120%. In other rats, the excitability was lower than that in the control from 4 msec to 15 msec. In fenvalerate treated rats, there was supernormal excitability from 4 msec to 40 msec. The peak of excitability was 122.4 +/- 35.3% at 10 msec. By double stimulation methods, we obtained characteristic nerve excitability changes in allethrin and fenvalerate treated rats after symptoms disappeared. These results showed that it should be possible to detect human nerve subclinical changes following lower doses or during chronic exposure. PMID- 7780864 TI - A study on indices of body fat distribution for screening for obesity. AB - In order to screen high risk obesity groups for coronary heart disease, the relationships between certain body fat distribution indices and coronary risk factors (CRFs) were analyzed. Body circumference at various measuring points and skinfold thickness were measured in 938 male clerical workers, and some indices of body fat distribution were calculated. The results are as follows: (1) The body mass index (BMI) showed the highest correlation with systolic blood pressure, and skinfold thickness showed a high correlation with serum total cholesterol (TC) and LDL-cholesterol. (2) In body fat distribution indices, the waist/stature ratio (WSR) showed the highest correlation with CRF measurements, especially with serum triglyceride (TG) and diastolic blood pressure (DBP). (3) WSR showed the highest sensitivity and specificity for screening for abnormal hypertension groups TG and TC. (4) There were significant differences in the mean value for all CRF measurements between the high WSR group (> = 0.49) and the low WSR group (< 0.49), and the rates for high CRF persons in the high WSR group were almost twice those of the low WSR group. These results show that WSR is useful for the screening for obesity to prevent coronary heart disease. PMID- 7780865 TI - Have typewriter--will travel. PMID- 7780866 TI - The consensus report: is it ever the last word? PMID- 7780867 TI - From thrombolytic megatrials to clinical policy-making: facing the facts. PMID- 7780868 TI - Management of the postmyocardial infarction patient: a consensus report--revision of 1991 CCS guidelines. PMID- 7780869 TI - Can practice patterns and outcomes be successfully altered? Examples from cardiovascular medicine. The Clinical Quality Improvement Network (CQIN) Investigators. AB - OBJECTIVE: To offer an attributive opinion of recent improvements in acute myocardial infarction (AMI) practice patterns and patient outcomes in the culture of an active health care research program. DATA SOURCES: Review of original clinical data from five sequential, consecutively enrolled, AMI patient cohorts at the University of Alberta Hospitals from 1987-93. DATA SYNTHESIS: Early cohorts had low use of trial-proven efficacious therapies for AMI, particularly among high risk older and female patients. Over time, there were continuous and marked increases in the use of efficacious therapies and decreased use of nonefficacious therapies, with a parallel decrease in mortality among high risk patients. CONCLUSIONS: In a large tertiary care hospital between 1987 and 1993 the use of evidence-based AMI therapy and survival in high risk patients significantly increased. The continuity and large size of these improvements in AMI practice patterns, compared with similar populations reported in the contemporary literature, suggest it is unlikely they were due to chance. Rather, intercurrent repeated measurement and reporting of key health care performance indicators, and initiation of explicit critical path AMI practice guidelines provide a more likely explanation. Future studies by a network of community and university investigators will test whether these findings are true for a broad AMI population and whether similar practice definition and improvement tools are effective for other cardiac problems, including the management of congestive heart failure. PMID- 7780870 TI - Evaluation of the reproducibility and accuracy of apex beat measurement in the detection of echocardiographic left ventricular dilation. AB - OBJECTIVE: To develop a standardized method for measuring the width of the apex beat and to determine its precision and accuracy in detecting echocardiographically determined left ventricular dilation. DESIGN: In the reproducibility study, two cardiologists blinded to each other's findings measured the apex beat. To determine accuracy, blind, independent assessment of apex beat measurement was compared with left ventricular enlargement determined by echocardiogram. PATIENTS: One hundred and four patients referred for echocardiogram for a wide variety of suspected cardiac abnormalities. MEASUREMENTS: The apex beat was measured with patients in a 45 degrees left lateral decubitus position; medial and lateral aspects of the impulse and the width were identified using electrocardiographic callipers. Echocardiographic left ventricular dilation was defined as a measure exceeding the 95% prediction limits as determined for the patient's age and body surface area. RESULTS: The intraclass correlation measuring agreement on apex beat size between two cardiologists in 13 patients was 0.95. Of the 104 patients, 57 had a measurable apex beat of whom 50 had a technically adequate echocardiogram. The sensitivity of the measurement, using a cut-point of 40 mm, was 0.48 and the specificity 0.96. PMID- 7780871 TI - Nonrheumatic atrial fibrillation: a brief overview. AB - OBJECTIVE: To review the effectiveness of current approaches in the treatment of patients with nonrheumatic atrial fibrillation (NRAF). DESIGN: Review of the available English-language articles on the epidemiology, clinical consequences, management and prevention of stroke in patients with NRAF. RESULTS: The incidence of atrial fibrillation increases steadily in both sexes in relation to age. The clinical independent risk factors for NRAF are diabetes mellitus, hypertension, recent heart failure, valvular heart disease and myocardial infarction. The echocardiographic predictors are left atrial enlargement, reduced left ventricular function and left ventricular wall thickness. The clinical consequences of NRAF are increased risk of stroke, mortality and left ventricular dysfunction. The management of NRAF includes correction of cause, termination of acute episode, maintenance of sinus rhythm, ventricular rate control and prevention of systemic embolism. CONCLUSION: NRAF is a common cardiac arrhythmia that is associated with high incidence of mortality and systemic embolism. Anticoagulation is effective in preventing embolism with acceptable risk of major bleeding. Acetylsalicylic acid is less effective but a reasonable alternative when anticoagulation is contraindicated. PMID- 7780872 TI - 2,3-Butanedione monoxime preserves coronary artery endothelium-dependent relaxation during myocardial ischemia in the isolated rat heart. AB - OBJECTIVE: To evaluate the potential benefit of 2,3-butanedione monoxime (BDM) in preserving endothelium-dependent coronary artery relaxation during myocardial ischemia. MATERIALS AND METHODS: Langendorff-perfused rat heart model. Endothelium-dependent and independent relaxations were tested with infusion of 5 hydroxytryptamine (10(-6) mol/L) and sodium nitroprusside (10(-5) mol/L), respectively. Four groups of hearts (n = 6) were used. Group 1 was perfused with BDM (25 mmol/L) without ischemia for 30 mins. Group 2 was perfused for 10 mins with BDM and exposed to 30 mins of no flow ischemia (37 degrees C). Group 3 was perfused with cold (4 degrees C) nonoxygenated BDM (30 mins) and group 4 (control) was exposed to 30 mins of no flow ischemia alone. Left ventricular pressure (LVP), left ventricular pressure first derivative (dP/dt) and coronary basal flow were evaluated before treatment and after 30 mins of reperfusion. RESULTS: BDM perfusion alone (group 1) did not affect coronary reactivity. Preservation of endothelium-dependent and -independent relaxation was significantly enhanced after ischemia in groups 2 and 3 (BDM-treated) compared with group 4 (control). No significant benefit was found regarding LVP and dP/dt in all groups. Postreperfusion coronary flow was decreased in all hearts except the controls (group 4), suggesting a residual BDM intrinsic effect on coronary flow. CONCLUSION: These experiments suggest that BDM can enhance preservation of coronary artery endothelium-dependent and -independent relaxation during myocardial ischemia in the isolated rat heart. PMID- 7780874 TI - Evaluation of MI therapy at a Canadian tertiary hospital. PMID- 7780875 TI - World Conference on Hypertension Control. Ottawa, Canada, June 21-24, 1995. Abstracts. PMID- 7780873 TI - Successful treatment of heparin-associated thrombocytopenia and thrombosis using Hirulog. AB - Heparin-associated thrombocytopenia is a serious medical problem, especially when the patient requires continued anticoagulation. Hirulog is an immediate-acting intravenous anticoagulant that can be substituted for heparin. A new use of Hirulog in the treatment of life-threatening heparin-associated thrombocytopenia with thrombosis (HATT) is presented. Two patients suffering from the HATT syndrome were successfully treated with Hirulog to prevent further thrombosis. A third patient had developed heparin-associated thrombocytopenia after coronary artery bypass surgery in the past and was subsequently treated with Hirulog during a peripheral angioplasty procedure. Hirulog was an effective and predictable anticoagulant for these patients and was free from adverse effects. PMID- 7780876 TI - How to reduce the risk factors of osteoporosis in Asia. AB - Osteoporosis can be predicted to be a new burden to public health in Asia. Currently, the incidence of osteoporosis-related fractures is lower there than in most western communities. By the year 2050, however, 50% of the 6.3 million hip fractures which occur worldwide will be in Asians as a result of an aging population, a decrease in physical activity and westernization of lifestyles. The cost of treatment and cure of these patients will be enormous, a sufficient financial burden to consume current economic gain and cripple the future advancing development of Asian countries. Individual risk factors for osteoporosis have been identified by the extensive Mediterranean Osteoporosis Study (MEDOS). Fortunately, Asians, the rural population and farmers in particular, have the favorable lifestyle identified by the study, including high physical activity and exposure to sunlight. Strikingly, tea drinking, a daily habit in Asia, is also identified as a protective factor against osteoporosis. In addition, bioflavonoids and phytoestrogen-rich soybeans and vegetables are consumed in large quantities by Asians. A soy diet reduces mortality in breast and prostate cancer because it contains weak estrogens. The weakly estrogenic phytoestrogens require further study to demonstrate their pharmacological effect in reducing the rate of osteoporosis. Public health education, however, is needed to encourage the Asian population to maintain their traditionally good lifestyle and to reduce the risk factors for osteoporosis. In turn, these steps may reduce the public health burden by 2050. PMID- 7780877 TI - Detection of antibody to M2 mitochondrial antigen in Chinese patients with primary biliary cirrhosis. AB - BACKGROUND: Antimitochondrial antibodies (AMA) are present in more than 90% of patients with primary biliary cirrhosis (PBC). However, AMA are not specific for PBC; they can be observed in nonhepatic disease. It has been reported that antibody of M2 mitochondrial antigen (anti-M2) is specific for PBC. The aim of the present study is to clarify the role of anti-M2 in the diagnosis of PBC. METHODS: Sera from 27 patients with PBC, 62 normal subjects, 18 patients with chronic hepatitis B and 30 patients with chronic hepatitis C were obtained for the detection of anti-M2 and AMA. The anti-M2 assay was performed by enzyme immunoassay (EIA) and the AMA test was performed by indirect immunofluorescent method. RESULTS: Twenty-four (88.9%) of the serum specimens from the patients with PBC and one (0.9%) of the 110 serum specimens from the non-PBC groups were positive for AMA. In contrast, twenty-five (92.6%) of the 27 PBC sera and five (4.5%) of the 110 non-PBC sera were positive for anti-M2. Most of the PBC sera contained high titers of anti-M2 and all the false-negative specimens disclosed low titers of anti-M2. CONCLUSIONS: Although the anti-M2 assay used in the present study seemed not superior to the conventional AMA test in the sense of specificity, it had the advantage of being able to provide quantitative results. Since the presence of high titer anti-M2 is very specific for PBC, this assay may have a role in the diagnosis of equivocal PBC. PMID- 7780879 TI - An appraisal of dipyridamole thallium imaging-detected ischemia in Chinese following acute myocardial infarction. AB - BACKGROUND: The detection of objective myocardial ischemia is an important work up of risk stratification for survivors of acute myocardial infarction (MI). Intravenous dipyridamole thallium scintigraphy was used to identify the prevalence and prognostic value of silent myocardial ischemia (SI) at the early stage in patients after MI. METHODS: Ninety patients (male/female = 87/3; aged from 36 to 70 years) who succumbed to an episode of MI was recruited in this prospective study. Thallium imaging with reversible or combined defect was defined as presence of SI (Group I), while those with fixed defects or normal images were defined as absence of SI (Group II). Correlation between the patterns of thallium images for postinfarct ischemia and the angiographic lesions was investigated. Also, versatile clinical variables and indexes of adverse cardiac events: unstable angina, CHF, reinfarction, ventricular tachyarrhythmia and sudden death, were evaluated for their influence on patients' prognosis. The average follow-up was 11.6 months. RESULTS: There were 61 patients in the Group I as compared with 29 patients in the Group II. The difference of Killip functional classification between Group I and Group II patients was not significant (1.33 +/ 0.72 versus 1.07 +/- 0.59). Adverse cardiac event occurred in 30% (27/90) of the patients during follow-up. Cardiac death occurred in 6 cases (7%) and were distributed evenly (3 versus 3) in both groups. Group I patients showed a higher number of nonfatal reinfarctions (8 versus 5) and had more cases of percutaneous coronary angioplasty (11 versus 8) than Group II patients. Only two cases in Group I underwent bypass graft surgery. There was no statistic difference among four patterns of thallium image in the cumulative event-free survival curve. Prior history of CHF, prior MI and higher score index of proximal arterial stenosis were the three significant prognostic predictors for late cardiac events. CONCLUSIONS: Dipyridamole thallium imaging-detected SI was frequently seen in the Chinese patients following AMI. It was less valuable than prior histories of CHF, prior MI and higher index of proximal arterial stenosis scores in predicting the short-term unfavorable cardiac events in these patients. A large scale analysis and longer follow-up might be required to more accurately determine the role of this exam for the Chinese victims of myocardial infarction. PMID- 7780878 TI - Polyethylene glycol method is superior to ammonium sulfate and protein-A sepharose-4B method in fractionating thyroid stimulating immunoglobulin in Graves' disease. AB - BACKGROUND: The purpose of this study is to compare the performance of three methods, i.e., ammonium sulfate, polyethylene glycol (PEG) and protein A sepharose 4B in fractionation of thyroid stimulating immunoglobulin. METHODS: Twelve patients with Graves' disease and twelve age-, sex-matched normal controls were recruited. 0.9 ml of saturated ammonium sulfate was added slowly to 1.1 ml of sera of all subjects and was stirred until reaching 45% saturation. The precipitation was allowed to form at 4 degrees C overnight. The solution was centrifuged at 10,000 x g for 5 minutes. The precipitate was washed twice with 45% ammonium sulfate, dissolved in 0.55 ml of distilled water equal to half of the initial volume of the serum and dialyzed against 200 volumes of phosphate buffered saline (PBS) for 48 hours. Another 0.5 ml of serum sample from the same patients was mixed with 1.5 ml of 20% polyethylene, followed by centrifugation at 2,800 g for 20 minutes. The pellet was dissolved in 0.6 ml of Hanks' medium without NaCl containing 1.5% bovine serum albumin, 20mM HEPES: 1 ml of sera was applied to 0.75 g of protein A sepharose-4B in PBS buffer and eluted with glycine, pH 2.3. By adding immunoglobulin (Ig) from the different methods to the FRTL-5 tissue culture, we determined the cAMP generation. RESULTS: Patients with Graves' disease were found to have higher serum thyroxine and triiodothyronine concentrations (p < 0.001) and significantly higher free thyroxine concentration than normal subjects. Ig elicited stronger response in cyclic AMP generation when prepared with PEG method, as compared with the other two methods (p < 0.001). With sepharose-4B Ig preparation, 10 out 12 patients (83.33%) showed positive thyroid stimulating immunoglobulin (TSI) while with ammonium sulfate precipitation, nine out 12 patients (75%) showed positive TSI. On the other hand, all patients showed positive TSI with PEG precipitation. When the degree of thyrotoxicosis was classified in terms of thyroid hormone concentrations, there was no correlation between TSI titers and thyroid hormone concentration. CONCLUSIONS: Polyethylene glycol is superior to both ammonium sulfate and protein A sepharose-4B in fractionating TSI in terms of sensitivity and convenience in operation. PMID- 7780880 TI - Use of a low profile Doppler angioplasty guidewire to evaluate the effect of percutaneous coronary angioplasty on coronary artery flow velocity. AB - BACKGROUND: The intracoronary Doppler flow velocity measurement is widely used. The Doppler flow catheter, used in many studies, still cannot always measure distal portions of coronary artery stenosis. However, three years ago, a low profile Doppler angioplasty guide wire (0.018-inch) was started by apply for measurement of changes in proximal and distal flow velocity during coronary angioplasty. METHODS: Blood flow velocity and diastolic/systolic velocity ratio (DSVR) on both proximal and distal portions of the coronary artery were measured with a low profile Doppler angioplasty guide wire in 13 patients with stenosis of the left anterior descending artery (LAD) during coronary angioplasty. RESULTS: Non-significant improvement in maximal peak velocity was noted in the distal portion of the coronary artery immediately after angioplasty (before, 36 +/- 12 cm/s; after, 41 +/- 12 cm/s; p > 0.05); but significant improvement was found after removal of the balloon (from 41 +/- 12 cm/s to 49.5 +/- 15 cm/s, p < 0.01). Increases in proximal maximal peak velocity after angioplasty were less remarkable (before, 38.5 +/- 15 cm/s; after, 45 +/- 13 cm/s; p > 0.05), and there was a significant increase of DSVR on the distal portion of the left anterior descending artery after angioplasty (before, 2.18 +/- 0.51; after, 2.98 +/- 0.44; p < 0.05). However, there was no significant increase of DSVR on the proximal portion of LAD (before, 2.19 +/- 0.16; after, 2.44 +/- 0.1; p > 0.05). The coronary flow reserve ratio showed no significant increase on the distal portion of the LAD (before, 1.03 +/- 0.3; after, 1.02 +/- 0.3) and proximal portion of LAD (before, 1.05 +/- 0.2; after, 1.03 +/- 0.3). CONCLUSIONS: Increase in peak velocity and DSVR of the distal portion of the coronary artery after angioplasty was more significant after removal of the balloon catheter than as if it were assessed immediately, without removing the balloon catheter. No significant increase in flow velocity of the proximal portion of the coronary artery after angioplasty was observed. No significant increase of the coronary flow reserve of the distal and proximal portion of the coronary artery occurred after successful angioplasty. PMID- 7780881 TI - Does coronary artery disease with stressed myocardial ischemia alter heart rate variability? AB - BACKGROUND: Research has shown that decreased heart rate variability (HRV) is independently associated with increased mortality after acute myocardial infarction. However, the relationship between HRV and myocardial ischemia still remains controversial. The purposes of this study were (1) to determine the relationship between HRV and atherosclerosis of the coronary artery; and (2) to determine the relationship between HRV and the extent of coronary stenosis in patients with stressed myocardial ischemia. METHODS: Forty-six patients, 41 males and 5 females, were included in this study. Ages ranged from 50 years to 79 years. Seventeen volunteers served as the control group, which was comprised of 15 males and 2 females of ages ranging from 40 years to 74 years. For each patient a left ventriculogram and a coronary angiogram were performed. According to their coronary angiograms, patients were divided into normal coronary artery group, atherosclerotic coronary artery group and significant coronary artery disease group. An ambulatory EKG was performed on each patient and volunteer. Heart rate variability was defined as SDNN, SDANN, rMSSD, and pNN50 in time domain measures; and low and high frequency in frequency domain measures. RESULTS: There were no significant differences in all variables of heart rate variability between the atherosclerotic coronary artery group and normal coronary artery group. In addition, there were no significant differences in all variables between the significant coronary artery disease group and the control group or between the significant coronary artery disease group and the normal coronary artery group. CONCLUSIONS: These studies have shown that atherosclerotic or significant coronary artery disease with stressed myocardial ischemia does not impair 24-hour heart rate variability. PMID- 7780882 TI - Clinical distinction between acute hemorrhagic and acute ischemic stroke by Siriraj stroke score. AB - BACKGROUND: The clinical distinction between hemorrhagic and ischemic stroke cannot be achieved by simple clinical evaluation, and it is impossible to submit all stroke patients to computed tomography. A simple, reliable, and safe diagnostic tool for acute stroke syndrome is needed. This study tested the Siriraj stroke score to verify its accuracy for distinguishing among the pathological subtypes of stroke. METHODS: This study included the one hundred and seventy-one patients with acute supratentorial stroke syndromes consecutively admitted to the Emergency Room of the Taichung Veterans General Hospital from April 1 to September 30, 1993. The Siriraj stroke score was calculated, then compared with results of computed tomography. The Siriraj stroke score was calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracranial hemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing further evaluation to verify diagnosis. RESULTS: The diagnostic sensitivities of the Siriraj stroke score for intracranial hemorrhage and infarction were 85% and 90% respectively, with an overall predictive accuracy of 88.5%. When three cases with subarachnoid hemorrhage whose scores were all above 1 were excluded, the sensitivities for cerebral hemorrhage and infarction were 83.8% and 90% respectively, with an overall predictive accuracy of 88.2%. CONCLUSIONS: The Siriraj stroke score can be used as a reliable bedside method for diagnosing acute stroke and for deciding which patients should have priority for computed tomography, it is also a valuable tool for epidemiology studies of stroke incidence and outcome. PMID- 7780883 TI - Fingertip reconstruction by the reverse digital artery island flap. AB - BACKGROUND: Fingertip injuries remain as one of the most common injuries in the hand. The ideal reconstruction for such injuries is to provide abundant tissue with similar qualities, preserve the length, maintain joint motion and restore fingertip sensation. Although many reconstructive methods are described in the literature, many disadvantages can be associated with these procedures. METHODS: An island skin on the side of the proximal phalanx, based on the ipsilateral digital artery, was elevated to resurface the defect of the fingertip. Six male patients with fingertip injuries were treated by using this flap from August 1993 to January 1994. Their ages ranged from 20 to 55 years. The average follow-up time was 8.5 months. RESULTS: Three of the six flaps were involved the middle fingers; two, for the index fingers and one, for the small finger. The sizes of the flaps varied from 1.5 by 2.0 to 2 by 3;. all the flaps survived. There was no vascular disturbance nor neurological deficit, and no limitation of joint motion. All the patients were pleased with the results. CONCLUSIONS: The advantages of the reverse digital artery island flap include using a single operative field on the injured digit, allowing for treatment of single or multiple fingertip injuries, providing abundant tissue with similar qualities and aesthetic improvement. PMID- 7780884 TI - Successful percutaneous transluminal angioplasty in native coarctation of aorta in young adult: a case report. AB - Coarctation of aorta is a rare cause of secondary hypertension, premature death will occur if no appropriate treatment is given. Before 1980, the only effective treatment was surgery, and recurrent stenosis was frequent. After then several works on percutaneous transluminal angioplasty of this disease were reported, with promising short-term and long-term results, especially in children and young adults. This report concerns a 19-year-old male who had hypertension for four years; the hypertension was caused by coarctation of the aorta, confirmed by cardiac catheterization and angiography. Average blood pressure (BP) of his upper extremities was 200/110 mmHg which dropped to 150/90 mmHg immediately, and still two years, after angioplasty, whereas BP of the lower extremities maintained at about 150/80 mmHg measured by Korotkoff technique. Follow-up transesophageal echocardiography found no coarctation or aneurysm at the dilatation site one year later. Magnetic resonance imaging, performed two years later, showed an almost normal aortic wall at the coaxctation. The postoperative course was uneventful, and patient follow-up at the cardiology clinic has regularly shown an average BP around 150/80 mmHg. PMID- 7780885 TI - Effect of calcitriol treatment on psoriasis in hemodialysis patient: a case report. AB - The case of a 67-year-old man who has had psoriasis with multiple joints involvement for 30 years and renal failure for 1 year is described. He was admitted because of uremic symptoms and exacerbation of psoriasis. Hypocalcemia and low serum active 1.25(OH)2D3 were also observed. Hemodialysis, oral 1.25(OH)2D3 and CaCO3 supplement were employed. Interestingly, the psoriasis strikingly improved. The relationships among psoriasis, renal failure, 1.25(OH)2D3, serum calcium level and dialysis are discussed. PMID- 7780886 TI - Cardiotoxicity related to 5-fluorouracil chemotherapy: a report of two cases. AB - 5-Fluorouracil (5-FU) is a chemotherapeutic agent which has been used to treat many solid tumors including cancers of the breast, ovary, cervix, bladder, prostate gland and gastrointestinal tract. Side effects related to the drug include bone marrow suppression, stomatitis, nausea, vomiting and diarrhea. However another less frequent but lethal event cardiotoxicity--appears to have been ignored by physicians. Recently, two cases of cardiac toxicity induced by 5 FU have been encountered here. One patient developed supraventricular tachycardia and the other illustrated silent myocardial infarction with congestive heart failure. Since these side effects may result in death when 5-FU is prescribed to those patients who have had previous heart disease or are concomitantly receiving inevitable radiotherapy over the cardiac region, it should be recommended with extreme caution. PMID- 7780887 TI - Elevated serum CK-MB and CK-BB isoenzymes in a patient with small cell lung cancer: a case report. AB - An increase in serum creatine kinase-MB (CK-MB) isoenzyme is regarded as a specific indication of acute myocardial infarction. Recently, increased concentrations of various types of creatine kinase isoenzymes (mostly CK-BB and macro CK type 2 isoenzymes) have been found in the blood of some patients with malignancies. However, highly elevated serum CK-MB isoenzyme associated with malignancy has rarely been reported previously. Herein a case of extensive small cell lung cancer is presented in which the elevated serum levels of CK were detected throughout the three weeks of hospitalization. Fractionation of its isoenzymes by gel electrophoresis displayed elevated CK-MB and CK-BB isoenzymes. The proportion of serum CK-MB and CK-BB isoenzyme activities was persistently above normal (CK-MB 50-53%, normal < 5%). Clinical examination showed no evidence of myocardial infarction or injury, or tumor involvement of the heart. The tumor was the probable source of most circulating CK-MB isoenzyme. In clinical practice, markedly elevated levels of CK-MB, or increased levels of CK-MB in combination with CK-BB may point away from a myocardial origin and toward the existence of a malignancy. PMID- 7780888 TI - Insufficiency fracture of acetabulum: a case report. AB - Most stress fractures of the hip joint occur on the femoral side. A review of the English literature showed that only eight cases of stress fracture of the acetabulum had been reported. Another insufficiency fracture of the acetabulum in an osteoporotic bone is reported. PMID- 7780890 TI - Update in cataract and refractive surgery. PMID- 7780889 TI - Torsion of an ovarian borderline tumor with extreme serum tumor markers: a case report. AB - A postmenopausal woman with torsion of the left ovarian mucinous cystadenoma with borderline malignancy is reported. Extremely elevated serum tumor markers such as carcinoembryonic antigen (CEA) (398.0 ng/mL, normal < 3.0 ng/mL), carbohydrate antigen 19-9 (CA 19-9) (240 U/mL, normal < 37 U/mL) and tissue polypeptide antigen (TPA) (1,918 U/L, normal < 110 U/L) were found preoperatively. Imaging studies such as ultrasound and computed tomogram favored a diagnosis of ovarian malignancy, and advanced ovarian cancer was suspected prior to operation. Diagnosis of borderline malignancy was first made by frozen section during laparotomy. The patient recovered following simple total hysterectomy and bilateral salpingo-oophorectomy. Serum levels of the tumor markers became normal gradually following operation. To present knowledge, this is the first reported case with extremely high serum tumor markers in a postmenopausal woman with torsion of a stage-Ia ovarian mucinous cystadenoma of borderline malignancy. Rapid release of these tumor markers into circulation secondary to necrosis and degeneration of the tumor cells following torsion might account for such an unusual finding. PMID- 7780892 TI - Natural course of perfused central retinal vein occlusion. AB - OBJECTIVE: To investigate the visual prognosis in perfused (nonischemic) central retinal vein occlusion (CRVO), to determine the frequency of conversion from perfused to nonperfused CRVO, and to identify risk factors for poor visual outcome. DESIGN: Case series. SETTING: Retina referral centre in Portland, Ore. PATIENTS: Fifty-eight patients (59 eyes) with perfused CRVO followed for at least 1 year (average 2.5 years). MAIN OUTCOME MEASURES: Visual acuity, progression to nonperfused CRVO. RESULTS: At the final follow-up visit the visual acuity had improved by two or more lines in 9 eyes (15%), remained the same in 33 eyes (56%) and decreased by two or more lines in 17 eyes (29%). Factors significantly related to visual outcome were initial visual acuity (p = 0.0001) and age, older patients having a worse visual outcome (p = 0.0029). Nine eyes (15%) progressed to nonperfused CRVO. None of the factors analysed, including age, sex, duration of symptoms and initial visual acuity, were predictive of progression. CONCLUSIONS: Perfused CRVO frequently results in significant, permanent visual loss, and a poor visual outcome is most likely in older patients and those with poor initial visual acuity. PMID- 7780891 TI - Perioperative ofloxacin vs. tobramycin: efficacy in external ocular adnexal sterilization and anterior chamber penetration. AB - OBJECTIVE: To compare the efficacy of two treatment regimens, tobramycin drops erythromycin ointment and ofloxacin drops-placebo ointment, in sterilizing the external ocular adnexa when given perioperatively. A second objective was to determine the aqueous humour concentration of ofloxacin and tobramycin. DESIGN: Randomized double-blinded clinical trial. SETTING: University-affiliated hospital. PATIENTS: Patients aged 18 years or more scheduled to undergo planned cataract surgery who were judged likely to complete the trial. NUMBERS: Of 55 patients enrolled 6 were disqualified and 49 completed the trial. INTERVENTIONS: Preoperative instillation of 10 drops of a 0.3% solution of ofloxacin (26 eyes) or tobramycin (23 eyes) in the operative eye, starting the evening before surgery. Tobramycin-treated eyes received erythromycin ointment after surgery; ofloxacin-treated eyes received petrolatum ointment. Lid and conjunctival swabs were obtained from both eyes on the day before surgery (visit 1), at surgery (visit 2) and on the first postoperative day (visit 3). Aqueous humour samples were obtained from the study eyes at surgery. MAIN OUTCOME MEASURES: Threshold growth of bacteria on culture, aqueous humour concentration of ofloxacin or tobramycin. RESULTS: At visit 1, 96% of all eyes had positive cultures; this result persisted at visits 2 and 3 for the control eyes. For the treated eyes the incidence of positive cultures decreased from visit to visit. By visit 3 lid cultures were positive for 7 (27%) of the ofloxacin-treated eyes and 7 (30%) of the tobramycin-treated eyes; conjunctival cultures were positive for 0 (0%) of the ofloxacin-treated eyes and 1 (4%) of the tobramycin-treated eyes. No significant differences were seen in culture positivity between the treatment groups at any visit. The mean aqueous humour concentration of ofloxacin was significantly higher than that of tobramycin (0.4084 vs. 0.0279 microgram/mL) (p < 0.001). CONCLUSIONS: Both ofloxacin-placebo treatment and tobramycin erythromycin treatment were more effective than no treatment in sterilizing the external ocular adnexa. The two treatments were equally efficacious in eliminating bacteria, more successfully in the conjunctiva than the lids. Topically administered ofloxacin demonstrated significantly greater anterior chamber penetration than topically administered tobramycin. PMID- 7780893 TI - Correction of night myopia and glare for night driving. AB - OBJECTIVE: To assess the effectiveness of treating night myopia. SETTING: Ophthalmic practice in Toronto. PATIENTS: Sixty-one patients aged 18 to 60 years with night myopia and no ocular disease followed for 1 to 14 months (phase 2). Phase 1 (32 patients) was abandoned because of problems with the tint chosen. INTERVENTIONS: Assessment of night myopia with a laser speckle generator, prescription of minus lenses with or without a tint. MAIN OUTCOME MEASURES: Magnitude of night myopia, subjective change in symptoms of night myopia. RESULTS: Nineteen patients (31%) could not benefit from minus or tinted lenses, and eight were lost to follow-up. Of the remaining 34 patients 22 (65%) reported marked improvement in night driving, 9 (26%) had moderate improvement and 3 (9%) had minimal improvement. CONCLUSIONS: Many patients with night driving difficulties can be helped with an increased myopic correction worn at night. PMID- 7780894 TI - Decreased retinal blood flow in retinitis pigmentosa. AB - OBJECTIVE: To determine alterations in retinal blood flow in retinitis pigmentosa (RP). DESIGN: Case-control study. SETTING: Ophthalmology department of a university-affiliated hospital in Elazig, Turkey. SUBJECTS: Ten patients (20 eyes) with typical RP and 22 age-matched volunteer subjects (22 eyes) with no history of ocular or systemic disease. MAIN OUTCOME MEASURES: Central retinal artery peak systolic and diastolic blood flow velocity (measured by means of colour Doppler imaging), resistance index and pulsatility index. RESULTS: The mean peak systolic and diastolic flow velocity values were significantly lower in the study group than in the control group (4.96 +/- 1.3 vs. 11.11 +/- 1.5 cm/s [p < 0.00001] and 2.15 +/- 0.4 vs. 3.40 +/- 0.9 cm/s [p < 0.0001] respectively). The mean resistance index value was significantly lower in the study group (0.55 +/- 0.05) than in the control group (0.71 +/- 0.06) (p < 0.0001), as was the mean pulsatility index value (0.94 +/- 0.18 vs. 1.45 +/- 0.36) (p < 0.00001). CONCLUSIONS: Decreased retinal blood flow is an important feature of RP. PMID- 7780895 TI - Acanthamoeba keratitis: increasing the index of suspicion. PMID- 7780897 TI - Functional visual loss and the duochrome test. PMID- 7780896 TI - Viscoelastic dissection for relocation of off-axis intraocular lens implant: a new technique. PMID- 7780898 TI - A survey of intraocular schwannoma with a case report. PMID- 7780900 TI - Excimer laser photorefractive keratectomy. PMID- 7780899 TI - Effects of cytoskeleton-reactive agents on aqueous outflow facility in a porcine ocular anterior segment preparation. AB - OBJECTIVE: To assess the effect of three agents known to react with cytoskeletal components--acrylamide (a vinyl monomer), demecolcine (a colchicine derivative) and stypoldione (an ichthyotoxic metabolite derived from the tropical marine alga Stypopodium zonale)--on facility of aqueous humour outflow in order to increase the understanding of the role of the cytoskeleton in the biology of aqueous outflow. DESIGN: Constant-pressure perfusion experiments with various concentrations of the agents using a porcine ocular anterior segment preparation. NUMBERS: Eighteen experimental eyes (six with each agent) and 18 control eyes. MEAN OUTCOME MEASURES: Aqueous outflow facility, determined after 1, 2 and 24 hours of perfusion. RESULTS: The mean baseline outflow facility was 0.10 (standard error of the mean 0.045) microL/min per mm Hg. There was no significant difference in mean baseline outflow facility between the experimental and control eyes. Perfusion of 0.01 to 1.0 mM demecolcine did not produce any consistent alteration in outflow facility. A mild to moderate dose-related experimental effect was noted after 2 hours of perfusion with 1.0 to 100 mM acrylamide. Perfusion with 0.10 mM stypoldione produced a moderate increase in outflow facility; the effect was greatest after 1 hour of perfusion. CONCLUSIONS: Our preliminary results do not support a central role for the cytoskeleton in the regulation of aqueous outflow resistance. PMID- 7780901 TI - Defining physician-assisted suicide and euthanasia. PMID- 7780902 TI - Misuse of asthma-medication inhalers. PMID- 7780903 TI - Sex differences in psychologic symptoms among patients with newly diagnosed lung cancer. PMID- 7780905 TI - Orthopractic organization seeking to usurp chiropractors? PMID- 7780904 TI - Orthopractic organization seeking to usurp chiropractors? PMID- 7780906 TI - Prevention and control of high blood pressure: challenges and opportunities. AB - Cardiovascular disease is still the leading cause of death in developed countries and is becoming more common in the developing world. The reduction in incidence of many cardiovascular diseases in the last few decades may be attributed in part to extensive programs to reduce and manage risk factors such as hypertension. Nevertheless, untreated, uncontrolled and undiagnosed hypertension remains a significant concern. Many nations have adopted policies and programs for hypertension control. An international sharing of knowledge and experience could lead to improvements in the prevention and treatment of hypertension and to lower rates of cardiovascular disease. In keeping with Canada's leadership in hypertension and cardiovascular disease prevention, Ottawa will host the World Conference on Hypertension Control from June 21 to 24, 1995. This conference will give participants the opportunity to review current programs and develop improved strategies for hypertension control and cardiovascular disease reduction. PMID- 7780907 TI - Monitoring clinical research: an obligation unfulfilled. AB - The revelation that data obtained for the US-based National Surgical Adjuvant Breast and Bowel Project (NSABP) from subjects enrolled at Hopital Saint-Luc in Montreal was falsified has eroded public trust in research. Institutions can educate researchers and help prevent unethical research practices by establishing procedures to monitor research involving human subjects. Research monitoring encompasses four categories of activity: annual reviews of continuing research, monitoring of informed consent, monitoring of adherence to approved protocols and monitoring of the integrity of data. The authors describe characteristics of research projects that may call for monitoring procedures in each category. The form taken by such monitoring depends on the nature of the protocol. Although appropriate research monitoring requires substantial investment of personnel and financial resources, it is required under guidelines regulating research involving human subjects in Canada. Research monitoring is a step forward in re establishing public confidence in medical research. PMID- 7780909 TI - Community surveillance for wild poliovirus in Ontario, 1993. PMID- 7780908 TI - New directions in research: report from the 10th International Conference on AIDS. AB - Research findings presented at the 10th International Conference on AIDS, held in Yokohama, Japan, in August 1994, indicate that few advances have been made in standard antiretroviral therapy for HIV infection. The perinatal administration of AZT (zidovudine) was reported to reduce transmission of HIV from mother to child, and its use in combination with acyclovir appears to improve survival among patients with advanced disease. Other research has focused on asymptomatic patients with long-standing HIV infection. Their survival may be related to the activity of cell antiviral factor, a cytokine produced by CD8+ cells. In gene therapy research, one approach involved the genetic alteration of target cells to enable them to render the virus harmless. A second approach consisted of enhancing the function of CD8+ cells to allow them to compensate for dysfunctional CD4+ cells. The author believes that gene therapy may offer the greatest hope of an effective treatment for HIV infection. PMID- 7780910 TI - Physicians among many participants in midst of Canada's emotional gun-control debate. AB - Because they are seen as advocates for public health and safety, physicians are also widely believed to be supporters of aggressive gun-control measures, but in reality there are strong feelings on both sides of the issue. "People assume that more gun control will mean less violence, but there are no hard data to support that," says Vancouver psychiatrist Joseph Noone, who argues that Canada already has highly restrictive firearms laws. Other physicians are puzzled by colleagues' opposition to the changes. "I don't understand why it's such a big deal," says Dr. Stephen Corber, medical officer of health for the Ottawa-Carleton region. He argues that registration would not be a deterrent to responsible gun use and ownership. PMID- 7780911 TI - It's 210 transplants and counting at the University of Ottawa Heart Institute. AB - The Ottawa Heart Institute, the site of more than 200 heart-transplant procedures since 1984, is preparing for the retirement of its founder, Dr. Wilbert Keon, in 2001. The institute has developed a national and international reputation, but also faces the same funding challenges as other Canadian health care facilities. Although the cost of the institute's high-tech procedures is challenged by some, Keon makes no apologies. "I haven't the slightest problem rationalizing what we do here," he says. "There are many areas in our health care system that should be tightened up before we cut services with demonstrable benefits." He also thinks there might be room for private care within Canada's publicly funded system. PMID- 7780912 TI - Is the issue the price of a child's life, or the futility of heroic measures? AB - Britain's High Court has been asked to rule whether a $160,000 experimental treatment with a 1% chance of saving the life of a 10-year-old girl should be paid for by the National Health Service. Child B, who has had one bone-marrow transplant, has had acute myeloblastic leukemia for a year and is near death. However, after her Cambridge doctors advised that further treatment would not be beneficial, her family found a hematologist willing to try an experimental treatment and a second transplant. The media debate in Britain has focused on financial aspects of the situation, not on the usually futile use of heroic measures. PMID- 7780913 TI - Altered keratinocyte growth and differentiation in psoriasis. PMID- 7780914 TI - T lymphocytes in psoriasis. PMID- 7780915 TI - The inflammatory infiltrate in psoriasis. PMID- 7780916 TI - Inflammatory mediators and chemoattractants. PMID- 7780919 TI - Pathogenic aspects of psoriasis. Introduction. PMID- 7780918 TI - Signal transduction pathways in epidermal proliferation and cutaneous inflammation. PMID- 7780920 TI - The puzzling genetics of psoriasis. PMID- 7780917 TI - Cell trafficking and role of adhesion molecules in psoriasis. PMID- 7780921 TI - Developmental care: making your NICU a gentler place. AB - Over the years, the nursing care provided at Women's College Hospital in Toronto has broadened to become increasingly holistic. Our neonatal intensive care unit (NICU) has kept pace. Seven years ago we introduced the philosophy of developmental care in the NICU, and it has continued to evolve ever since. This framework of care not only makes us more effective in meeting the neurodevelopmental needs of preterm infants, it also leads to enhanced relationships between parents and their babies. PMID- 7780922 TI - Latex allergy alert. AB - Reports of children and adults having allergic reactions after latex exposure are appearing in the literature in increasing numbers. The reactions have ranged from rashes, hives and swelling to respiratory distress and even death. Unfortunately, although latex is a common component in many hospital and household products, many health care workers remain unaware of the potential implications of latex allergy on their work and on the health and safety of their patients. PMID- 7780923 TI - The silicone breast implant controversy. AB - Feminists call it objectification. Consumer advocates call it victimization. Medical personnel call it augmentation. Women, implantation. Whatever the term, media hype and the increasing number of lawsuits against U.S. manufacturers of silicone breast implants has caused widespread concern among women and raised serious questions about the long term health risks and safety of breast implant devices. PMID- 7780924 TI - Breast implants: a gender issue? AB - Breast implants have been in use in Canada for more than 30 years. Between 100,000 and 200,000 Canadian women have them as well as one to two million women in the United States. Oddly, despite those numbers, inadequate data are available on the safety and side effects of these prosthesis. PMID- 7780925 TI - [Facing perinatal bereavement]. AB - Pregnancy and childbirth are, for most women, wonderful and memorable experiences. Yet, without warning, they can have a heartbreaking outcome. Regardless of the stage of pregnancy at which a baby is lost, the family grieves the death. The authors of this article suggest how nurses can best support the couple, siblings, grandparents and significant others through their time of sorrow. The article highlights key points from the 1992 the Hopital de Chicoutimi (Quebec) reference guide entitled "Guide d'accompagnement des familles devant un deuil perinatal." The guide includes the types of grief and the six phases of grief resolution. It outlines specific nursing interventions and recommends various strategies for the nurse to help these families grieve their loss. Some strategies include the holding and cuddling of the baby by the parents, post partum follow-up by nursing personnel and family therapy sessions. The authors suggest that nurses who are knowledgeable about the grief experiences of these parents will be better equipped to help other parents cope with similar grief. The increased knowledge will also assist nurses to sort out and deal with their own feelings on this subject. Nurses who are able to effectively care for these grieving families can often enhance their personal and professional self-esteem. PMID- 7780926 TI - [How to intervene effectively with a dying patient]. AB - Nurses are in a strategic position to meet the needs of the dying patient. However, when confronted with death, nurses often utilize avoidance behaviors, such as: tending to the dying patient only if a technique is required; initiating conversations on casual topics or directing the conversation towards the patient's "health"; requesting consults to avoid talking about dying; and unnecessarily overmedicating the patient. This paper explains the rights and needs of the dying patient and describes associated nursing interventions. For example, the dying patient has the primordial right to choose whether or not to receive treatment. For nurses to intervene effectively, they must learn to manage their own emotions relating to death. A strong theoretical understanding of the dying process must be acquired. They must also develop internal strengths and receive help from various resources. By doing so, nurses reinvest their shared life experiences and apply them to other dying patients continuously refining their conceptual model of loss. Through verbal and non-verbal cues, nurses transmit profound messages to their patients. Some efficient nursing interventions consist of: providing basic care and medications to prevent terminal suffering; offering an attentive and reassuring presence; respecting the contemplative phases; listening for latent messages in conversations; understanding symbolic language; respecting family dynamics; allowing family members to choose physical and psychosocial interventions to improve the patient's comfort; frequently visiting the patient and intensifying their presence; permitting the dying patient to verbalize fears and anxieties; and consistently offering tenderness, empathy, acceptance, warmth and respect. As death nears, scientific and technological aspects of nursing become less important for the patient, and the art of sincere human empathy becomes paramount. PMID- 7780927 TI - The body reality. PMID- 7780928 TI - Seeing deafness in a new light. PMID- 7780929 TI - The glass box. PMID- 7780931 TI - Recovery's limitations. PMID- 7780930 TI - Suspicious death. PMID- 7780932 TI - From vision to reality. PMID- 7780933 TI - Nursing in Nepal. AB - In 1991 and '92 I developed and implemented a research project that was a case study of nurses and primary health care in Nepal. Data were gathered from a variety of sources, but what I found particularly interesting were the interviews with nurses and my observations of them at work. PMID- 7780934 TI - "Wish you were here...". AB - Camp is one of the most popular summer destinations for children and youth. Their enthusiasm is infectious; more and more adults are now taking part. Summer camp offers a change of pace (not always slower); a change of environment (not always outdoors); and, a change of expectations (where else could you wear the same clothes for a whole week?). It's also a chance to be accepted as you are, or try new roles with no expectation of perfection. Little wonder that camp appeals to all ages. PMID- 7780935 TI - Alcohol home detoxification. AB - Traditional inpatient treatments for alcohol-related problems often prevent the problem drinker from seeking early intervention. Inpatient treatment may be particularly difficult for women because of stigma, labelling and family commitments. An alternative, home-based program initiated in the United Kingdom (U.K.) in the late 1980s and currently being trialed by many health districts, may be of interest to Canadian nurses. In addition to improved client outcomes and cost-effectiveness, the program offers nurses a higher public and medical profile. Clinical nurse specialists in particular may want to consider whether the expanded role of their British colleagues might be appropriate for Canadian adaptation. PMID- 7780936 TI - [The nurse manager in oncology]. AB - Several nursing studies have described the important role of the oncology nurse manager in managing nursing staff. A 1987 study by Vachon, outlined stressors identified by 581 health professionals working in oncology units. It identified the fact that nursing personnel face a workplace filled with pain and suffering on a daily basis. The study concluded that the oncology nurse manager is the key individual to encourage a climate of sharing and support among nursing staff. Oncology nurse managers are role models and mentors who transmit to their staff the desire for a caring and holistic approach to excellence in patient care. Professional, educational and personal responsibilities rest with them. They must maintain a dynamic presence with all members of the health care team. Their knowledge of the most current medical breakthroughs, as well as strong leadership qualities, inspire nursing staff to strive for high standards of care. PMID- 7780937 TI - Reform and primary care. AB - The success of Canada's health care reform depends on nurses' participation. No one can dispute that nurses are the largest single group of health care providers. Nurses are also experienced players in primary health care-health care's new direction. PMID- 7780938 TI - Clearer images in pediatric MRI. AB - Pediatric outpatient magnetic resonance imaging (MRI) was a frustrating experience for both patients and staff at London, Ontario's University Hospital until nurses, the child-life specialist, physicians and technicians got together and developed the Pediatric MRI Sedation Program. PMID- 7780940 TI - One strong voice. PMID- 7780939 TI - Standard of care. AB - Did you know that a nurse may be held to the same standard of care as a physician? In a 1989 Indiana case, Planned Parenthood of Northwest Indiana, Inc. v. Vines 543 N.E. 2d 654 (Ind. App. 3 Dist. 1989), a patient and her husband sued a clinic and a nurse for negligence in the insertion of an intrauterine device. The Indiana Court of Appeals upheld a lower court's finding that the nurse practitioner be held to the standard of care of a physician in performing this procedure. PMID- 7780941 TI - The power of hope. AB - What would it be like to know the day of our death? How would that feel, knowing that each passing day brought you closer to that final day? I hope may last day comes as a surprise. PMID- 7780942 TI - Long term care in acute care facilities. PMID- 7780943 TI - Rationing health care. AB - What health services should governments pay for? Who should receive transplants or expensive procedures? What services should be available through private insurance? Should there be a two-tiered system? And, how do we decide on what services to publicly insure/fund? Many governments around the world are facing such questions. In Canada, the Government of Alberta and the Reform Party of Canada have recently expressed the need to re-think which health services are publicly funded, or the "comprehensiveness" of Canada's health care system. PMID- 7780944 TI - Segmentation and visualization of brain lesions in multispectral magnetic resonance images. AB - In this study we focus on the problem of segmentation and visualization of soft tissue structures in three-dimensional (3D) magnetic resonance (MR) imaging. We introduce a classification method which is a combination of a recently proposed contour detection algorithm and Haslett's contextual classification method extended to 3D. This classification method is used in the classification step of a rendering model suggested by Drebin et al. for visualizing normal and pathological tissue structures in the brain. We evaluate the combination of these two methodologies, and identify some problems which have to be solved in order to develop a clinical useful tool. PMID- 7780945 TI - Rapid automatic brain volumetry on the basis of multispectral 3D MR imaging data on personal computers. AB - Fast magnetic resonance imaging sequences are an excellent basis for the volumetry of the human brain. We present a concept for an automatic three dimensional (3D) segmentation and volumetry which provides rapid image processing along with minimal requirements of manual interaction on low-end hardware platforms. The concept is based on standard image segmentation techniques and provides for the determination of the total brain tissue and cerebrospinal fluid volumes from the input data base, a T1- and a T2-weighted 3D image data cube. We used a 3D MPRAGE sequence for the T1- and a 3D PSIF sequence for the T2-weighted images; both 3D image data cubes consisted of 128 sagittal image slices with a voxel size of 1.0 x 1.0 x 1.2 mm3. The segmentation and volumetry tool was applied to clinical image data of volunteers and Alzheimer patients in order to prove its stability. PMID- 7780946 TI - Three-dimensional densitometric reconstruction and visualization of stenosed coronary artery segments. AB - In this paper we report results from an ongoing study about the diagnostic benefits of three-dimensional (3D) visualization and quantification of stenosed coronary artery segments. Biplane angiographic images do not provide enough information for the exact reconstruction of the coronary arteries. Therefore, a priori information about the 3D shape to be reconstructed must be incorporated into the reconstruction algorithm. One approach is to assume a circular cross section of the coronary artery. Hence, the diameter is estimated from the contours of the vessel in both projections. Another approach is based on densitometry and searches for a solution of the reconstruction problem close to the previously reconstructed adjacent slice. In this paper we apply contour information as well as the densitometrical profiles of the two orthogonal vessel projections. We present a new probabilistic densitometric reconstruction algorithm, which extends the correct handling of the stochastic properties of the density profiles into the network flow based reconstruction algorithm. The reconstructed coronary segment is visualized in three dimensions. In order to assess the accuracy of the reconstruction, the method is applied to tubes with artificial obstruction of known geometry, modeling coronary artery stenoses. These catheter tubes are filled with normal iodine contrast material. The results of the reconstruction and visualization are discussed with respect to clinical usefulness. PMID- 7780947 TI - MR relaxometry: estimating overhydration in renal failure. AB - An MR method is described for estimating overhydration in patients suffering from renal failure. In 29 healthy volunteers, the fat content of a selected slice of the lower limb was correlated to the overall T1-relaxation time (r = -0.97, p < 0.000001). When compared with the normal T1 of the voluntary group, delta T1 was calculated having regard to the individual fat content in 74 MR studies of 22 overhydrated patients. MR results were correlated with the difference between clinically estimated dry and the actual body weight (r = 0.6, p < 0.000001). In an intraindividual follow-up (11 studies) MRI was shown to provide good correlation to the actual body weight (r = 0.9, p < 0.0005) and fluid balance (r = 0.87, p < 0.001). PMID- 7780948 TI - Light photon equalization and its application to X-ray film digitization. AB - The principle of light photon equalization (LPE) is to modulate the light source during X-ray film digitization so that the dynamic range of the transmitted light into a photo-detector can be precisely controlled to obtain improved signal-to noise ratio (SNR). The modulation of the light source is derived from a smoothed image of the original digitized image. The final output digital image is reconstructed by convoluting the modulation function with the resultant LPE image. The LPE was implemented in a laser film digitizer as a prototype. The results shows that, although the dynamic range of X-ray films is about 10(4):1, the range of the transmission light into a photo detector was reduced to 10(2):1 with this technique. Also the SNR improved by a maximum factor of five in the lung area of a digitized chest radiograph. PMID- 7780950 TI - Unruptured interstitial pregnancy: a pitfall of MR imaging. AB - We report two cases with interstitial pregnancy, which showed completely different MR appearances. In case 1, a gestational sac was demonstrated and the diagnosis of ectopic pregnancy was straightforward. In case 2, a hypervascular mass was shown without demonstration of a gestational sac, the findings usually seen in gestational trophoblastic disease (GTD). MR imaging may play some role in the diagnosis of interstitial pregnancy when sonography is insufficient or equivocal. If GS is visualized, diagnosis is easy. However, if not, the appearance may have a spectrum and can be similar to GTD. PMID- 7780949 TI - Solitary muscular involvement by tuberculosis: CT, MRI, and scintigraphic features. AB - The authors reported computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphic findings of a patient with solitary muscular tuberculosis in the forearm. All these findings resembled those of other granulomatous inflammatory lesions in the soft tissue such as muscular sarcoidosis. PMID- 7780951 TI - MR findings in hereditary spherocytosis. AB - The magnetic resonance findings of intrathoracic extramedullary hematopoiesis associated with bone marrow reconversion, and reticuloendothelial hemosiderosis in a 50-years-old are reported. Radiologic finding of extramedullary hematopoiesis was the first step to the diagnosis of previously unknown hereditary spherocytosis. PMID- 7780953 TI - Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy. AB - This study investigated the in vitro and in vivo radiation response of tumor cells transfected with human manganese superoxide dismutase (MnSOD) cDNA. A major objective was to test the potential tumor suppressive effect of MnSOD in vivo. Tumor cells studied were an in vitro line derived from a murine spontaneous fibrosarcoma, FSa-II, which expressed an undetectable MnSOD activity. These cells were transfected with pSV2-NEO plasmid (NEO line) or cotransfected with MnSOD plasmid plus pSV2-NEO plasmid (SOD lines) as described previously. The cell lines used were SOD-L and SOD-H, which expressed, respectively, low and high MnSOD activities after transfection, and NEO and parental FSa-II controls. Both SOD-L and SOD-H cell lines were slightly more resistant to ionizing radiation than were the two control cell lines when irradiated in vitro in the presence of oxygen. The dose-modifying factors calculated at the survival level of 0.01 were 1.13 and 1.15 for the SOD-L and SOD-H cells, respectively. To investigate potential tumor suppressive effects, animal tumors of 4 mm diameter were irradiated in vivo under hypoxic conditions, and the radiation dose to control one-half of the irradiated tumors (TCD50) was determined for each tumor. The TCD50S obtained on the basis of the tumor control rate in 120 days after irradiation were substantially lower for the SOD-H and SOD-L tumors compared to the NEO tumors. They were 22.9, 28.6, and 47.5 Gy for SOD-H, SOD-L and NEO tumors, respectively. To analyze these data, survival curves were obtained for hypoxic cells by irradiating NEO and SOD-H tumors under hypoxic conditions in vivo and assaying in vitro. Analysis of these curves suggests that the decrease in the TCD50S of SOD tumors is attributable to the reduced tumorigenicity in these tumors. The hypoxic cell survival curves also showed that SOD did not protect cells from radiation in the absence of oxygen. Electron microscopy showed no morphological differences between these cells. These results suggest that the fraction of tumorigenic cells could be reduced by expression of MnSOD, resulting in a substantial decrease in the TCD50. PMID- 7780954 TI - A defined region of loss of heterozygosity at 11q23 in cutaneous malignant melanoma. AB - Karyotypic and molecular data indicate that genetic alterations of the long arm of chromosome 11 (11q) may be involved in malignant melanoma. To test this we analyzed 5 polymorphic microsatellite repeats on 11q using a PCR-based assay for loss of heterozygosity in normal and tumor tissues from 24 individuals with cutaneous malignant melanoma of various stages. Our findings indicate that a tumor suppressor gene that plays a role in malignant melanoma is located on the long arm of chromosome 11, likely within a 51 cM region at 11q23. Its loss appears to be a late event in tumor progression and may serve as an indicator for a less favorable clinical outcome. PMID- 7780952 TI - Effects of estrogen on apoptotic pathways in human breast cancer cell line MCF-7. AB - We utilized a reverse transcription-PCR method to examine the effect of estrogen on the expression of mRNA for Bcl-2 and Bax, two modulatory proteins in the apoptotic pathway, in human breast cancer cell line MCF-7. We found that the bcl 2 mRNA levels in the cells exposed to 17 beta-estradiol were higher than those of control cells. Although the relative bax mRNA levels remained unchanged, the changes in bcl-2 mRNA level occurred in a time- and concentration-dependent fashion. In addition, pretreatment with 17 beta-estradiol protected MCF-7 cells from apoptosis. Our study provides evidence that responses of breast epithelial cells toward a steroid sex hormone involve regulation of the apoptotic pathway. PMID- 7780955 TI - Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas. AB - Chromosomal aberrations involving the chromosomal breakpoint region 12q14-15 are frequently seen in a variety of mesenchymal tumors as uterine leiomyomas, lipomas, myxoid liposarcomas, enchondromas, or hemangiopericytomas. Therefore, this breakpoint region seems to be one of the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in cells of three pulmonary chondroid hamartomas with 12q14-15 aberrations, we performed fluorescence in situ hybridization analysis with different cosmid clones originating from a YAC and cosmid contig overspanning parts of the region 12q14 15. We were able to narrow down the breakpoint to a region of 175 kb belonging to an area designated multiple aberration region because it also includes the breakpoints of leiomyomas, lipomas, and pleomorphic adenomas with 12q14-15 abnormalities. Our molecular and cytogenetic data suggest that hamartomas of the lung molecularly belong to the benign group of mesenchymal tumors showing multiple aberration region involvement. PMID- 7780956 TI - p21CIP1 is not required for the early G2 checkpoint response to ionizing radiation. AB - We have previously reported that the immediate G2 checkpoint delay of normal human fibroblasts in response to ionizing radiation is correlated with inhibition of p34CDC2/cyclin B kinase activity. Here, we observed increased amounts of the cyclin-dependent protein kinase inhibitor p21CIP1 associated with p34CDC2/cyclin B protein complexes from irradiated normal human fibroblasts. Since wild-type p53 function is not required for the early G2 checkpoint response to ionizing radiation, we investigated whether a p53-independent induction of p21CIP1 was required for the G2 checkpoint. Early passage human fibroblasts expressing the E6 oncoprotein of human papilloma virus-type 16 (NHF4 E6) were analyzed. It has been demonstrated earlier than inactivation of wild-type p53 function in these cells by E6 protein does not alter their intact early G2 checkpoint response to gamma rays. p21CIP1 was found to be undetectable in p34CDC2/cyclin B protein complexes and in total extracts from the E6-expressing cells, with or without exposure to ionizing radiation. These data indicate that p21CIP1 is not required for the immediate G2 checkpoint response and is not induced by a p53-independent pathway in G2 phase following exposure to gamma-rays. PMID- 7780957 TI - Mutational effects on the p16INK4a tumor suppressor protein. AB - Several point mutations of p16INK4a were studied by site-specific mutagenesis and functional analysis to assess the effects of these mutations on the function of the protein. These mutations were reported in several malignancies. Three deletional mutants of p16INK4a were also analyzed to reveal the relationship between p16INK4a and p15INK4b and to test the importance of the ankyrin repeats observed in both proteins. We studied the activity of these mutants using the yeast two-hybrid system and an in vitro kinase assay. Our results suggest that point mutations in the conserved ankyrin consensus affect the activity of p16INK4a. However, not all of the point mutations observed in tumors have a detectable effect on the activity. The COOH-terminal region of p16INK4a is not required for the protein to bind and to inhibit CDK4, but the deletion of the 4th ankyrin repeat abolished the activity completely. PMID- 7780958 TI - Overexpression of Bcl-XS sensitizes MCF-7 cells to chemotherapy-induced apoptosis. AB - Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. We used Bcl XS, a dominant negative inhibitor of Bcl-2 and Bcl-XL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Bcl-XS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. Using an ELISA assay which quantitates DNA damage, we demonstrate that this sensitization is due to apoptosis, suggesting the therapeutic utility of targeting this pathway. PMID- 7780959 TI - Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile. AB - Although gallbladder carcinoma is one of the most frequent neoplasms in Chile, there is limited information about the molecular changes involved in its pathogenesis. We investigated the incidence of ras gene mutations and loss of heterozygosity (LOH) at the following genes/loci: p53, DCC, rb, 5q 3p, 8p, and 9p. We precisely microdissected 194 relevant areas from paraffin-embedded microslides from 25 gallbladder carcinomas and their accompanying nonneoplastic lesions (which were present in 15 cases) from patients in Chile. The specimens were analyzed by PCR-based assays for LOH, and we designed a RFLP method for ras mutations and immunohistochemistry for p53 protein overexpression. We determined that LOH at p53 (91%), 9p (50%), 8p (44%) and DCC (31%) are frequent events and that LOH at p53, 9p, and DCC are early events, while ras mutations and LOH at 3p, rb, and 5q occurred occasionally. LOH at p53 occurred more frequently and earlier than protein overexpression. The mean number of mutations present in invasive carcinomas was 2.1, and in six cases, LOH at the p53 gene was the sole mutation detected. The same allele was lost in 61 (93%) of 71 nonneoplastic foci as in the corresponding invasive carcinomas for all four mutations studied. The odds of this occurring by chance are approximately 4 x 10(-15). Although clonality cannot be excluded, allelic loss appears to be highly directed, but the mechanism for allele-specific mutations remains to be determined. PMID- 7780960 TI - Selective cell culture of primary breast carcinoma. AB - We have used culture conditions which simulate the microenvironment of breast tumors for the isolation and propagation of primary breast tumor cells in vitro. In this monolayer setup, the mixture of cells dissociated from primary breast tumors is subjected to self-created gradients of oxygen and nutrients as well as metabolic waste and extracellular pH. The tumor populations isolated under these novel conditions have displayed phenotypic properties characteristic of breast carcinomas, including homogeneous expression of cytokeratin 19, and increased mitochondrial retention of the cationic dye rhodamine 123. Nonmalignant cultures from reduction mammoplasty were unable to survive these conditions. One tumor population which reached passage 10 was aneuploid for chromosomes 15 and 17, and displayed a p53 mutation in exon 8. These studies strongly suggest that the culture conditions described here can suppress the growth of normal breast cells, thereby allowing selective isolation of some populations of slow-growing primary tumor cells in vitro. PMID- 7780961 TI - Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate. AB - Metastasis is an inefficient process; only a few cancer cells are able to form tumors after being released into the circulation. We studied the fate of cancer cells after injection into the circulation, quantifying their survival and ability to extravasate by 1 day later. B16F10 cells, parental or transfectants overexpressing tissue inhibitor of metalloproteinases 1, were injected i.v. into chorioallantoic membrane of chick embryos and analyzed by intravital videomicroscopy. Cell survival was quantified in two ways: (a) 15-microns microspheres were injected with cancer cells, and proportions of viable cells to microspheres were compared before and after injection; and (b) individual cancer cells were monitored continuously for 0.5-8-h intervals covering the first 24 h. Both methods showed virtually no destruction of cells. Greater than 80% of injected cells survived and extravasated by 24 h, indicating that growth after extravasation is a key stage of metastatic control. PMID- 7780962 TI - Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I. AB - In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the human T-lymphotropic virus type I pX gene, undifferentiated mammary carcinomas developed predominantly in females starting at about 5 months of age, and there was massive infiltration of granulocytes in the tumor tissue. The incidence of the tumor reached about 40% when the rats were 12 months old. mRNAs of both pX and host genes Gro and MIP-2, which are granulocyte chemoattractants of the interleukin 8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and the antioncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. PMID- 7780963 TI - Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression. AB - Epithelial cell kinase (ECK) is a receptor protein tyrosine kinase, the role of which in melanoma biology is unclear. Here we studied the role of ECK during melanoma progression. ECK mRNA was overexpressed in virtually all melanoma lines tested, and levels were significantly higher in cell lines from distant metastases than primary melanomas; melanocytes were negative. Gene amplification was not detected in melanomas. Levels of ECK protein corresponded well with mRNA levels. B61 or LERK-1, recently identified as an ECK ligand, stimulated the growth of ECK-expressing melanoma cell lines, its first identified biological activity. Melanoma chemotaxis and chemoinvasion were not affected by B61. Growth of normal melanocytes was not affected. mRNA for B61 was detected in both melanoma cell lines and normal melanocytes. B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media. These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes. PMID- 7780964 TI - Telomerase activity associated with acquisition of malignancy in human colorectal cancer. AB - Shortening of telomeres may contribute to the control of the proliferative capacity of normal cells, and telomerase, the enzyme that elongates telomeric DNA, may be essential for unlimited cell proliferation. We have shown previously that telomerase activity is present in human cells immortalized in vitro and in metastatic ovarian carcinoma cells but is undetectable in normal cultured cells or normal tissues. We have determined the temporal pattern of telomerase activity during colorectal carcinogenesis in man. We report that telomerase activity is associated with acquisition of malignancy as it is detectable in colorectal carcinoma but not in adenomatous polyps. Mutations leading to reactivation or upregulation of the enzyme may represent an additional required event in the multistep development of colorectal cancer. PMID- 7780965 TI - Differential expression of elafin in human normal mammary epithelial cells and carcinomas is regulated at the transcriptional level. AB - Elafin is an elastase inhibitor with a unique structure, not related to the serpin family, which includes the neutrophil elastase inhibitor. The gene was identified in this laboratory by subtractive hybridization between RNAs from human mammary tumor-derived cells and cDNAs from normal human mammary epithelial cells. Elafin is consistently expressed in normal mammary epithelial cells, but is down-regulated in most breast tumor cell lines. Restriction fragment analysis detected no gross deletions or rearrangement of the gene in any of the tumor cell lines examined. The elafin gene was cloned, and both the cDNA and the promoter region were sequenced. A major positive upstream promoter element was identified by chloramphenicol acetyltransferase assay and deletion analysis, active in normal cell extracts but not in extracts of tumor cells. These results demonstrate that differential expression of elafin in normal mammary epithelial cells and breast tumor cells is regulated at the transcriptional level. Cell synchronization experiments demonstrated that elafin mRNA is down-regulated in S phase in normal cells. These results suggest that elafin may act as an inhibitor of cell cycle progression. PMID- 7780966 TI - An alternatively spliced form of NQO1 (DT-diaphorase) messenger RNA lacking the putative quinone substrate binding site is present in human normal and tumor tissues. AB - DT-diaphorase is a ubiquitously expressed flavoenzyme responsible for the two electron reduction of a number of quinone and other anticancer drugs. The majority of DT-diaphorase enzyme activity in human tissues is the product of the NQO1 gene. We have now identified a novel alternatively spliced form of human NQO1 mRNA lacking exon 4 at levels equal to or exceeding those of wild-type NQO1 mRNA. Exon 4 codes for the putative quinone substrate binding site of DT diaphorase derived from NQO1 and the recombinant protein from alternatively spliced NQO1 mRNA lacking exon 4 has minimal enzyme activity with quinoid and other known substrates of DT-diaphorase. The physiological substrate of DT diaphorase is unknown, and it is possible that the protein derived from the alternatively spliced NQO1 mRNA could have enzyme activity with an appropriate substrate. We found full-length DT-diaphorase protein but could not detect expression of an appropriately smaller form of DT-diaphorase in human tissues using polyclonal antibody to DT-diaphorase, suggesting that alternatively spliced NQO1 mRNA lacking exon 4 may not be translated or that the protein product is rapidly degraded. Alternative splicing of NQO1 RNA could provide an important mechanism for regulating NQO1 gene expression. PMID- 7780967 TI - Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). AB - The M(r) 72,000 (MMP-2; gelatinase A) and M(r) 92,000 (MMP-9; gelatinase B) gelatinases are two members of the family of matrix metalloproteinases (MMPs). These proteinases are thought to play a critical role in tumor cell invasion and are frequently coexpressed in human cancers. Gelatinases are secreted in a latent inactive form, and their conversion to the active species can be accomplished by other proteolytic enzymes, including other MMPs. We report herein that organomercurial or plasma membrane-activated M(r) 72,000 gelatinase A activates progelatinase B to an M(r) 82,000 active form in a process inhibited by tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Progelatinase B activation was accomplished by the two active species of gelatinase A, the M(r) 62,000 and M(r) 45,000 forms, generated after plasma membrane or organomercurial activation of TIMP-2-free progelatinase A. The M(r) 45,000 species of gelatinase A lacks both the NH2-terminal profragment and the COOH-terminal domain known to play a role in plasma membrane activation and the regulation of TIMP-2 inhibition. These results suggest a novel mechanism of activation of progelatinase B mediated by gelatinase A species that may be localized in the surface of tumor cells and enhance matrix degradation during cancer metastasis. PMID- 7780968 TI - Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. AB - Prostaglandin G/H synthase (PGHS), a key enzyme leading to the formation of prostaglandins, is the target of nonsteroidal antiinflammatory drugs. Two forms of the enzyme have been identified, PGHS-1 and PGHS-2. Epidemiological evidence has suggested that aspirin and other nonsteroidal antiinflammatory drugs may reduce the risk of colorectal cancer. We examined by immunoblot analyses the expression of human PGHS-1 and PGHS-2 protein in 25 matched colon cancer and nontumor tissues, 4 premalignant polyps, 5 control colon tissues from noncancer patients, and 3 matched normal and cancerous breast tissue samples. PGHS-1 was detected in all normal and tumor tissue. In contrast, PGHS-2 was not detected in 23 of 25 normal colon tissues but was detected in 19 of 25 colon tumors. PGHS-2 protein was not observed in four human premalignant polyp samples, control colon from noncancer patients, or matched normal or cancerous breast tissues. These results suggest that the beneficial effects of nonsteroidal antiinflammatory drugs in colon cancer may be mediated by inhibition of PGHS-2. PMID- 7780970 TI - A mutator phenotype characterizes one of two complementation groups in human cells tolerant to methylation damage. AB - Sixty % of clones isolated from HeLa cells treated with toxic concentrations of a methylating carcinogen showed increased resistance to the cytotoxicity of N methyl-N-nitrosourea. D37 values were 6- to 100-fold higher than in the parental cell population. The absence of detectable levels of the repair enzyme O6 methylguanine-DNA methyltransferase indicated that the resistant clones were able to tolerate the presence of O6-methylguanine in their DNA. Analysis of N-methyl-N nitrosourea survival in the hybrids between tolerant clones and HeLa cells showed that tolerance can be either recessive or codominant. Fusion between tolerant clones indicated two complementation groups. We measured spontaneous mutation rates at microsatellites and at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in several tolerant clones. All the clones of Complementation Group I showed unstable microsatellites and 4-8-fold increases in mutation rates at hprt. No significant alterations in spontaneous mutation rates were found in clones of Complementation Group II. The data indicate that tolerance to methylation damage can be conferred by alterations in at least two different gene products and that one of the two groups has the mutator phenotype typical of mismatch correction defective cells. PMID- 7780969 TI - Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas. AB - Pancreatic ductal adenocarcinomas induced in the Syrian golden hamster (SGH) by N nitrosobis(2-oxopropyl)amine share many similarities with the human disease, including mutations of the K-ras oncogene. In vitro carcinogenesis studies with immortal SGH pancreatic duct cells indicate that neoplastic transformation in this system can occur without mutational inactivation of p53 suppressor gene. In this study we extend the genetic analysis of the in vivo SGH model to increase the number of cases analyzed for the status of K-ras and to determine further the spectrum of alterations involved; we have studied the status of the p53, DCC, and Rb-1 suppressor genes and the status of the mdm2 oncogene, which can involve p53 indirectly. The partial SGH-coding sequence of mdm2 and DCC was determined. K-ras mutation in the second position of codon 12 was present in 17 of 19 (90%) of tumors. Immunohistochemistry and single strand conformation polymorphism analysis showed no evidence of p53 mutation in 21 tumors. RNase protection assays showed overexpression of mdm2 in 5 of 19 (26%) tumors. Semiquantitative reverse transcription-PCR analysis showed a complete or partial loss of DCC expression in 10 of 19 (53%) neoplasms and of Rb-1 (42%) expression in 8 of 19 tumors when compared to matched controls. Deregulation of these genes appears to be significant in SGH pancreatic carcinogenesis as indicated by their frequencies. However, the fact that 6 tumors showed either only a K-ras mutation or the absence of alterations of the 5 genes analyzed indicates that additional as yet unstudied or unknown genes are also involved in SGH pancreatic duct carcinogenesis. PMID- 7780971 TI - Bcl-xL is expressed in neuroblastoma cells and modulates chemotherapy-induced apoptosis. AB - bcl-x is a new member of the bcl-2 gene family and is highly expressed in neural tissues. The present study was designed to determine the expression of the bcl-x gene products in neuroblastoma (NB) and their role in the modulation of chemotherapy-induced apoptosis. Twenty-seven NB cell lines were screened by quantitative immunoprecipitation for Bcl-xL, Bcl-xS, and Bcl-2 expression. None of the cell lines expressed Bcl-xS. Twenty-four of 27 (88%) of the NB cell lines expressed Bcl-xL and 21 of 27 (78%) were positive for Bcl-2. The level of Bcl-xL and Bcl-2 expression was variable among the lines analyzed. Bcl-2 expression was restricted to cells of chromaffin lineage, whereas Bcl-xL was seen in both chromaffin and nonchromaffin lines. To determine whether Bcl-xL could mediate chemotherapy resistance, a NB cell line expressing negligible levels of Bcl-xL was transfected with a bcl-xL expression vector, and unique clones were generated expressing variable levels of Bcl-xL. Cells were treated either with cisplatinum (CP), 4-hydroperoxy-cyclophosphamide (4-HC), or etoposide (VP-16) to induce apoptosis, and cell viability and DNA degradation were determined. Following treatment with CP or 4-HC, Bcl-xL-expressing cells showed significantly increased viability as compared to vector-transfected controls (P < 0.005). Flow cytometric analysis of propidium iodide-stained nuclei following CP or 4-HC treatment revealed significantly increased DNA degradation in controls as compared to Bcl xL-expressing lines (P < 0.004). DNA analysis by pulsed-field gel electrophoresis revealed high molecular weight (approximately 40 kb) DNA degradation in controls, whereas the DNA in cells expressing Bcl-xL was largely intact. In contrast to CP and 4-HC, results with VP-16 revealed a short-term delay in the onset of apoptosis in Bcl-xL-expressing cells with no long-term survival advantage. The results of these studies indicate Bcl-xL is expressed in NB cells and functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. PMID- 7780972 TI - An estrogen-independent MCF-7 breast cancer cell line which contains a novel 80 kilodalton estrogen receptor-related protein. AB - Long-term growth of estrogen-responsive human breast cancer cell lines in estrogen-free media leads inevitably to the development of estrogen-independent growth. We have identified and characterized a unique subclone of the MCF-7 human breast cancer cell line, named MCF-7:2A, which grows maximally in the absence of endogenous estrogens but whose growth is inhibited by the antiestrogens 4 hydroxytamoxifen and ICI 164,384. The MCF-7:2A cells express high levels of estrogen receptor (ER; 477 fmol/mg protein), which can be reduced by growth in 10 nM 17 beta-estradiol (201 fmol/mg protein). Basal progesterone receptor synthesis is very low in the 2A cells (< 1 fmol/mg protein) but can be dramatically increased by 10 nM 17 beta-estradiol (384 fmol/mg protein). Clearly, the pathways that control growth and estrogen-regulated genes such as the progesterone receptor are now dissociated in these cells. MCF-7:2A cells also possess two unique characteristics. First, the MCF-7:2A cells constitutively activate an ER responsive luciferase reporter construct in the absence of any estrogens, and this activation can be blocked by either 4-hydroxytamoxifen or ICI 164,384. This constitutive activity is not observed in the parental MCF-7 cells. Second, they express an 80-kDa protein that cross-reacts with three distinct antibodies to the ER. The MCF-7:2A cells were subjected to an additional round of limiting dilution subcloning, and 10 independent clones were all shown to express both the 66- and 80-kDa ERs as observed in the MCF-7:2A line. This confirms that both ERs are being expressed in each cell and are not the result of a mixed population of cells. While numerous ER variants have been reported previously, no ER has until now been described that is larger than the wild-type 66-kDa ER. The MCF-7:2A cells provide a unique model to use in the study of ER action and the development of estrogen-independent growth in human breast cancer cells. PMID- 7780973 TI - Prolactin synthesis and secretion by human breast cancer cells. AB - A possible autocrine function of prolactin (Prl) in human breast cancer was explored by the addition of a panel of anti-human Prl mAbs to T47Dco and MCF7 human breast adenocarcinoma cells. mAb 631 and mAb 390 inhibited cell growth by 86 and 68%, respectively, in the estrogen receptor-negative T47Dco cells and by 20 and 71%, respectively, in the estrogen receptor-positive MCF7 cells. Conditioned medium prepared from T47Dco cells was assessed for the presence of Prl-like molecules by its ability to stimulate growth of Prl-responsive Nb2 rat lymphoma cells. Growth of Nb2 cells under the influence of human Prl or conditioned medium was abolished when either solution was pretreated with mAb 390, followed by Immunobead precipitation (Bio-Rad, Melville, NY). T47Dco cells secrete 0.7 microgram lactogen/ml over a 24-48-h period. With the use of reverse transcription-PCR, an expected 612-bp band was detected by ethidium bromide staining, and its similarity to pituitary Prl was confirmed by Southern blot analysis with the use of human Prl cDNA as a probe. A single M(r) 22,000 band, the dominant size of monomeric pituitary Prl, was found in immunoprecipitates of both cell extracts and conditioned medium from T47Dco cells labeled metabolically with [35S]cysteine. These data suggest that human breast cancer cells synthesize and secrete biologically active Prl. PMID- 7780974 TI - Modulation of transforming growth factor beta 1 effects on prostate cancer cell proliferation by growth factors and extracellular matrix. AB - Poorly differentiated MATLyLu rat prostate cancer cells are resistant to the growth inhibitory effect of transforming growth factor (TGF) beta 1 in vivo, but are inhibited by TGF-beta 1 in vitro. However, TGF-beta 1 inhibited proliferation only when the cells were plated at low density in serum-free medium (concentration for 50% of maximum inhibition, 0.1 ng/ml). TGF-beta 1 was not growth inhibitory when cells were plated at high density, or at low density in 0.5% serum. At low cell density in serum-free medium, 0.5 ng/ml TGF-beta 1 caused maximum inhibition. In the presence of basic fibroblast growth factor (10 ng/ml), TGF-beta 1 did not inhibit proliferation. In the presence of epidermal growth factor (50 ng/ml), TGF-beta 1 inhibited proliferation by only 18%. Growth inhibition by TGF-beta 1 was less effective on extracellular matrix than on plastic. The ability of high cell density, serum, growth factors, or extracellular matrix to prevent or blunt the growth inhibitory effect of TGF-beta 1 in vitro probably explains why TGF-beta 1 does not inhibit tumor growth in vivo. Thus, prostate cancer cells express high levels of TGF-beta and retain exquisite sensitivity to the growth inhibitory effect of TGF-beta, but have devised a way to protect themselves from growth inhibition by TGF-beta in vivo. TGF-beta 1 stimulated MATLyLu cell motility even at high cell density, suggesting that TGF-beta 1 might affect motility even in vivo and contribute to the aggressiveness of the tumor, without affecting proliferation. PMID- 7780975 TI - Antimelanoma effect of 4-S-cysteaminylcatechol, an activated form of 4-S cysteaminylphenol. AB - Rational chemotherapy of malignant melanoma could be developed by taking advantage of the presence of melanogenic enzymes in melanoma cells. 4-S Cysteaminylphenol (4-S-CAP) has been evaluated for melanocytotoxicity and antimelanoma effect. Although 4-S-CAP is selectively toxic to pigmented melanoma cells, it is not potent enough when applied as a single agent. To increase the efficacy of 4-S-CAP, we synthesized 4-S-cysteaminylcatechol (4-S-CAC), an activated form of 4-S-CAP, and compared its biochemical properties and antimelanoma effects with those of the isomers 3-S-cysteaminylcatechol (3-S-CAC) and 2-S-cysteaminyl-hydroquinone (2-S-CAH). 4-S-CAC was found to be a better substrate for melanoma tyrosinase than was L-3,4-dihydroxyphenylalanine, the natural catecholic substrate. 3-S-CAC was a poor substrate, whereas 2-S-CAH was not a substrate. 4-S-CAC was the most cytotoxic to three lines of melanoma cells in vitro, followed by 2-S-CAH and 3-S-CAC. When applied i.p. for 9 days at a dose of 100 mg/kg, 4-S-CAC.HCl, increased by 46-52% the life span of C57BL/6 mice inoculated i.p. with B16 melanoma; this effect was comparable to that of a 50 mg/kg dose of 5-(3,3-dimethyltriazenyl)-1H-imidazole-4-carboxamide. 3-S-CAC was marginally effective, whereas 2-S-CAH was toxic to the host. This systemic toxicity of 2-S-CAH reflected its susceptibility to autoxidation. Growth of B16 melanoma cells inoculated s.c. was significantly inhibited by i.p. administration of 4-S-CAC.HCl (200 mg/kg) for 5 days (P < 0.05). These results suggest that 4-S CAC is a potent antimelanoma agent, the effect of which is mostly mediated through tyrosinase oxidation. PMID- 7780976 TI - Retrovirus-mediated expression of a DNA repair protein in bone marrow protects hematopoietic cells from nitrosourea-induced toxicity in vitro and in vivo. AB - Severe and delayed myelosuppression is a major side effect encountered with the clinical use of nitrosourea-type chemotherapeutic drugs. The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) has been shown to repair nitrosourea-induced DNA damage. We therefore investigated the effect of expressing MGMT in hematopoietic cells (via retrovirus-mediated gene transfer) on nitrosourea-induced toxicity. A retroviral vector (N2/ZipPGK-MGMT) expressing the human MGMT cDNA from the phosphoglycerate kinase promoter was constructed. Infection of murine bone marrow with the N2/ZipPGK-MGMT retrovirus significantly increased the survival of murine bone marrow-committed progenitor cells following in vitro exposure to N-N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine). MGMT gene transfer also protected murine hematopoietic cells in vivo in a murine model of BCNU-induced myelosuppression. The infusion of 4-6 x 10(6) N2/ZipPGK MGMT-transduced bone marrow cells into mice every 2 weeks significantly increased peripheral leukocyte counts, platelet counts, and hematocrits compared to infusions of mock-infected bone marrow cells. In addition, bone marrow-committed progenitor cells from some recipient animals demonstrated increased resistance to BCNU in vitro when analyzed 2.5 months after initial treatment. The integration of the N2/ZipPGK-MGMT provirus in the spleen DNA from these animals correlated with committed progenitor cell resistance to BCNU. These data suggest that MGMT expression in hematopoietic progenitor and precursor cells protects against nitrosourea-induced toxicity and that gene transfer may prove useful in attempts to reduce nitrosourea-induced myelosuppression in the clinical setting. PMID- 7780977 TI - Inhibition of the growth of various human and mouse tumor cells by 1,15 bis(ethylamino)-4,8,12-triazapentadecane. AB - Effects of 1,15-bis(ethylamino)-4,8,12-triazapentadecane (BE3333), the least toxic bis(ethyl)pentaamine, on the growth of tumor cells were studied in in vitro systems and with tumor xenografts in mice. BE3333 suppressed ornithine decarboxylase and S-adenosylmethionine decarboxylase, induced spermidine/spermine N1-acetyltransferase, and thus decreased the amount of polyamines. BE3333 accumulated in cells at a concentration 3-5-fold that of spermine in control cells through the polyamine transport system. The accumulated BE3333 inhibited protein synthesis, especially mitochondrial protein synthesis, and decreased the amount of ATP. The inhibition of protein synthesis was correlated with the subsequent inhibition of cell growth. BE3333 showed inhibitory effects in in vitro systems against the growth of mouse FM3A mammary carcinoma cells, human SW480 and SW620 colon tumor cells, Lu-65A and A549 lung tumor cells, MCF-7 breast tumor cells, and MALME-3M and A375 melanoma cells at a range of 0.5-10 microM. Intravenous (30 mg/kg) or i.p. (50 mg/kg) daily injections of BE3333 for 5 or 7 days greatly suppressed the growth of human colon tumor SW620 xenotransplanted into nude mice. Similar antitumor activity was obtained with continuous infusion of BE3333 into the peritoneal cavity (80 mg/kg), but not with p.o. administration (200 mg/kg). BE3333 also showed inhibitory effects against the growth of lung tumors (Lu-65, Lx-1, Lc-1, and Lu-61), stomach tumors (Sc-6 and St-15), and melanoma (SEKI) xenotransplanted into nude mice. The results indicate that BE3333 is effective against both rapid- and slow-growing tumors, with reasonable short term host toxicity. PMID- 7780978 TI - Uptake, localization, and photodynamic effect of meso tetra(hydroxyphenyl)porphine and its corresponding chlorin in normal and tumor tissues of mice bearing mammary carcinoma. AB - By using a chemical extraction assay and confocal laser scanning fluorescence microscopy, the kinetic patterns of uptake, elimination, and localization of meso tetra(hydroxyphenyl)porphine (m-THPP) and its corresponding chlorin (m-THPC) in tumors and various normal tissues of female C3D2/F1 mice bearing CaD2 mammary carcinoma were studied after an i.p. injection of either 5 mg/kg body weight of m THPP or 1 mg/kg body weight of m-THPC. Moreover, the histological and ultrastructural alterations of the tumors were evaluated after photodynamic therapy (PDT) with m-THPP or m-THPC. The PDT efficacy with m-THPP and m-THPC was also compared. Both m-THPP and m-THPC had a similar kinetic pattern of distribution in the tumors and most normal tissues examined. The concentrations of the dyes in the tissues peaked at 24-48 h after injection. The peak values of the uptake of m-THPP by the tissues were found to decrease in the following order: spleen > urinary tract > kidney > liver > lung > tumor > heart > skin > muscle > brain. However, higher concentrations of m-THPC were taken up by the tumors than by most of the normal tissues studied except for the liver, urinary tract, and skin. m-THPP was mainly localized in the stroma of the tumors, whereas m-THPC was distributed in both vascular interstitium and neoplastic cells of the tumors. Morphological studies showed that PDT with m-THPP resulted in destructive changes in the microvasculature of the tumors, whereas m-THPC-based PDT destroyed both vascular walls and tumor cells of the tumors. The m-THPP-PDT of the tumors was much less efficient than m-THPC-PDT of the tumors, although the dose of m THPP used was five times higher than that of m-THPC. m-THPP and m-THPC have different efficiency of sensitizing tumors to photodestruction, although they are similar with respect to hydrophobicity. This is likely due to the differences in their intratumoral localization patterns and in their absorption spectra. PMID- 7780979 TI - Suppressive role of the metastasis-related nm23-H1 gene in human ovarian carcinomas: association of high messenger RNA expression with lack of lymph node metastasis. AB - The nm23-H1 gene has been proposed as a metastasis suppressor gene. It is located on the long arm of chromosome 17, which is frequently deleted in ovarian cancer, and shows altered expression and structure in some advanced neoplasms. To evaluate the role of nm23-H1 in ovarian carcinogenesis, we have analyzed this gene in 66 primary human ovarian carcinomas at both the DNA and RNA levels. Despite the high frequency (76%) of nm23-H1 loss of heterozygosity (LOH), the complete absence of gene mutations in the coding portions of the retained allele clearly indicated that, in ovarian carcinomas, this gene does not function in the same way as do classic oncosuppressor genes. The relationship of clinicopathological parameters with nm23-H1 gene deletions and expression levels was also investigated. LOHs were more common in the serous and endometrioid histotypes (85 and 93%, respectively), and the highest LOH frequency was detected in poorly differentiated tumors (89%). A significant relationship between nm23-H1 mRNA expression and lymph node metastasis was observed in high-grade tumors, which are intrinsically more invasive than are low-grade tumors. In particular, among the poorly differentiated tumors showing areas of undifferentiated solid carcinoma (classified as G3/G4), lymph node-negative tumors displayed expression levels that were significantly higher than those of lymph node-positive tumors (P < 0.001). In conclusion, our data suggest that the nm23-H1 gene product may exert an inhibitory effect on the lymphatic dissemination of human ovarian tumors. However, several other factors, biological or time and patient dependent, influence the complex metastatic progression of ovarian tumors and may cooperate with nm23-H1 in the promotion or inhibition of this process. PMID- 7780980 TI - Identification of an enhancer responsible for tumor marker gene expression by means of transgenic rats. AB - The glutathione transferase P (GST-P) gene is known for its specific expression during chemical hepatocarcinogenesis of the rat and is used as a tumor marker for hepatocellular carcinoma. We have shown recently that the upstream 2.9-kb region of the GST-P gene is sufficient for conferring tumor-specific expression of the gene in vivo (S. Morimura et al., Proc. Natl. Acad. Sci. USA, 90: 2065-2068, 1993). To further identify crucial sequence elements regulating the unique expression of this gene, we have established six independent lines of transgenic rats bearing distinct areas of the GST-P gene that are connected to the chloramphenicol acetyltransferase coding region and analyzed changes of the chloramphenicol acetyltransferase activity during the course of chemical hepatocarcinogenesis. We demonstrate here that the enhancer, glutathione transferase P enhancer I, that is located 2.5 kb upstream of the GST-P gene is required and sufficient for its tumor-specific expression of the gene among other controlling elements. This approach to transgene expression could be used to define other enhancers, the activity of which is dependent on cellular changes such as carcinogenesis, development, and differentiation. PMID- 7780981 TI - Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma. AB - Studies of sequential molecular alterations in noninvasive and invasive head and neck squamous carcinoma are few in number. Consequently, the genetic changes associated with the neoplastic transformation of these carcinomas have not been defined. To identify chromosomal alterations in preinvasive and invasive head and neck squamous carcinoma, we analyzed DNA from microdissected normal squamous epithelium, severe dysplasia, and invasive carcinoma samples from 20 patients for loss of heterozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 9q, 11q, 17p, 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10%), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor stage, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, 8p, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tumorigenesis; (b) 9p loci alterations are manifested in the early development of these tumors; (c) LOH is correlated with poor prognostic clinicopathological factors; and (d) LOH at 8p loci appears to be associated with the tumor's aggressive features. PMID- 7780982 TI - Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis. AB - A common feature of the malignant progression of human tumors is loss of heterozygosity (LOH) for various regions of their genomes. Such events encompassing chromosomes 11p15 and 11q23 are frequent in human breast tumors. Here, we have analyzed genetic and clinical characteristics of a series of primary breast tumors in order to determine: (a) a more finely mapped estimate of the involved regions; (b) whether there is a relationship in the presentation of LOH between the two regions; and (c) whether a correlation exists between such LOH and any of the clinical parameters pertaining to each patient. We found that LOH for 11p15.5 and 11q23 occurred in 35 and 46% of the 86 primary breast carcinomas, respectively, but in none of the 10 benign tumors examined. The minimal region of LOH for 11p15 was in the approximately 2-megabase region between loci TH and D11S988. Twenty-nine % of the tumors showed LOH simultaneously at both 11p15 and 11q23, 5% had LOH only at 11p15.5, and 15% had LOH only at 11q23. Among these genetic groups, clinical features such as tumor size, involvement of auxiliary nodes, histological subtype, tumor grade, estrogen/progesterone receptor status, and patient age were not markedly different. However, LOH of 11q23 (either alone or in conjunction with LOH of 11p15) in the primary tumor was found to be highly predictive of aggressive postmetastatic disease course with substantially reduced survival (P = 0.0004; log rank test). We also observed a slight trend toward a more rapid development of metastatic lesions, without obvious site specificity, in patients with primary tumors showing LOH for chromosome 11 in the pathogenesis of human breast cancer; we suggest that its effects are late in the progression of this disease. PMID- 7780983 TI - Mutations of the K-ras and p53 genes in gastric adenocarcinomas from a high incidence region around Florence, Italy. AB - K-ras and p53 gene mutations in intestinal-type gastric carcinomas from a high incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single-strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (including two at a previously unreported site in codon 11), a significantly higher frequency than reported in countries other than Japan. No K-ras mutations were identified in stage III tumors. Single-strand conformation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, with mutations identifiable by direct sequencing in 65% of the cases. Of these, 91% were base substitutions, a value similar to that usually reported, but the percentage of G:C to A:T transitions (90% in this study, 89% in all published European cases combined) differed significantly from that in Oriental cases (48%). The percentage of A:T to G:C transitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European tumors). The frequency of mutations at CpG sites (14%) varied significantly from the 67% in cases from a neighboring region in Italy. Helicobacter pylori infection was established in 19 cases and was somewhat more common in cases lacking a p53 mutation. PMID- 7780984 TI - Identification of a monoclonal antibody, TV-1, directed against the basement membrane of tumor vessels, and its use to enhance the delivery of macromolecules to tumors after conjugation with interleukin 2. AB - mAbs reactive with epitopes expressed on tumor vessels were evaluated as universal delivery agents of peptides with vasoactive properties to enhance the uptake of macromolecules in tumors. Unlike other reported approaches to target tumor vessels, a mAb designated TV-1 targets a basement membrane antigen that is found in all tissues but that is accessible only in tumor vessels, making it an alternative vehicle for the delivery of biologically active peptides to tumors. A panel of 30 monoclonal and polyclonal antibodies was screened by immunohistochemistry on sections of human tumors, normal vascular endothelium, and connective tissues. Five antibodies were chosen for in vivo evaluation, including two antifibronectin antibodies (TV-1, HFN 7.1), one anti-basic fibroblast growth factor antibody (anti-BFGF), and two antibodies reactive with a mesenchymal cell antigen (TP-1, TP-3). Three nude mouse tumor models characterized by varying degrees of vascularization (low to high) were used. After chemical conjugation to interleukin 2 (IL-2), these antibodies were used to pretreat tumor-bearing nude mice 3 h before injection with a radiolabeled mAb directed to the transplanted tumors. Pretreatment with TV-1/IL-2 or HFN 7.1/IL-2 produced a 3-fold higher tumor uptake of radiolabel compared to control mice pretreated with mAb alone. The other three vasoactive immunoconjugates failed to show significant increases in these tumor models. When TV-1/IL-2 was compared with the specific vasoconjugate (Lym-1/IL-2) as a pretreatment in the Raji lymphoma model, which has low vascularization, TV-1/IL-2 yielded approximately 60% of the tumor uptake seen with Lym-1/IL-2. In comparison, pretreatment with TV 1/IL-2 in the LS174T colon carcinoma model, which has high vascularization, yielded approximately the same tumor uptake seen with the B72.3/IL-2 vasoconjugate, which directly targets the tumor cells. These studies demonstrate that a mAb directed against fibronectin in the endothelial subcellular matrix can be used to deliver vasoactive agents to tumors. PMID- 7780985 TI - Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. AB - Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and metastases. Human mucins are derived from a heterogeneous family of genes, labeled MUC1-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens. Probes and antibodies for specific mucin tandem repeat sequences were used for RNA and immunohistochemical analysis. Normal stomach mucosa was characterized by expression of MUC1, MUC5, and MUC6 mRNA and immunoreactive protein, without MUC2, MUC3, and MUC4 gene expression. In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metaplasia. Gastric cancers exhibited markedly altered secretory mucin mRNA levels compared with adjacent normal mucosa, with decreased levels of MUC5 and MUC6 mRNA and increased levels of MUC3 and MUC4 mRNA. Overall, immunoreactive MUC1 mucin was detected in 72% of 33 gastric cancers, and secretory mucin core peptides were expressed in 34% (MUC2), 45% (MUC3), 19% (MUC5), and 57% (MUC6) of these specimens. Coexpression of multiple (three or more) mucin core proteins occurred in 15 of 25 (60%) advanced (stages III and IV) cancers compared with 1 of 8 (12.5%) early (stages I and II) cancers (P < 0.048). We conclude that human gastric epithelium has a unique mucin gene pattern, which becomes markedly altered in preneoplastic and neoplastic specimens. Increased mucin gene heterogeneity in gastric adenocarcinomas is associated with advanced cancer stage. PMID- 7780986 TI - Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation. AB - The expression of peripheral-type benzodiazepine receptor (PBR) and diazepam binding inhibitor (DBI) were studied in human astrocytic tumors using immunocytochemistry and in situ hybridization. Both PBR and DBI were prominently expressed in neoplastic cells, whereas in normal brain their amount was low or undetectable. Immunocytochemical double staining demonstrated that PBR and DBI were present in the same cells, suggesting that DBI may act in an autocrine manner in these cells. Analysis of 86 cases showed that PBR expression was statistically significantly associated with tumor malignancy grade (P = 0.004) and the proliferative index as determined by immunocytochemistry with the MIB-1 antibody (P = 0.004). Patients having tumors with high levels of PBR immunoreactive cells had a shorter life expectancy than patients whose tumors showed lower PBR contents (P = 0.024). In conclusion, these results show that PBR expression is higher in neoplastic cells than in normal brain tissue. They also suggest that PBR immunocytochemistry might be useful in evaluating malignancy in brain tumors. PMID- 7780987 TI - Glutathione S-transferase pi in colorectal tumors is predictive for overall survival. AB - Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of xenobiotics and are divided into four subclasses, alpha, mu, pi, and theta, with different although overlapping substrate specificities. Most human gastrointestinal tumors contain increased amounts of GST-pi and GST enzyme activity. The relationship between GST parameters and tumor and patient characteristics, including overall survival, were studied retrospectively in 100 primary colorectal adenocarcinomas. Levels of GST-alpha, GST-mu, GST-pi, and GST enzyme activity were not related to the Dukes stage, differentiation grade, localization, histological type and diameter of the tumor, or gender and age of the patient. Fifty-seven patients died (median survival, 21 months; range, 1-65 months) during follow-up, and 43 patients were still alive at the closing date of the study (median follow-up, 68 months; range, 60-87 months). Optimal dichotomization and uni- and multivariate analyses were done with the Cox proportional hazard model. Multivariate analysis with all clinicopathological parameters revealed higher Dukes stage (hazard ratio, 2.7; P < 0.001) and older age (hazard ratio, 2.8; P = 0.001) to be the only independent prognostic variables for overall survival. In contrast to GST-alpha and GST-mu, high levels of GST-pi (hazard ratio, 3.1; P = 0.002) and GST enzyme activity (hazard ratio, 2.0; P = 0.020) in the tumors were found to have a significant prognostic value independent from the clinicopathological parameters when added separately to this Cox model. Thus, this study indicates that GST subclass levels in colorectal adenocarcinomas are not related to clinicopathological parameters and that the GST-pi level and GST enzyme activity have a prognostic value for the overall survival of the patients. PMID- 7780989 TI - Synthesis of 3,4-di-O-acetyl-2,5-anhydro-1,6-dideoxy-1,6-diiodo-D-mannitol. Comparison of NMR spectral results for the solid state and solution with those of the X-ray structural determination. AB - 3,4-Di-O-acetyl-2,5-anhydro-1,6-dideoxy-1,6-diiodo-D-mannitol (3) is prepared from 2,5-anhydro-D-mannitol (1) in three steps. The solution and solid-state NMR spectra of 3 indicate considerable variation in conformation. In solution, it adopts, on average, a symmetric 4T3 conformation, whereas in the solid state it adopts an asymmetric conformation as revealed by 13C NMR cross polarization and magic angle spinning techniques. A single-crystal X-ray structure analysis confirmed the asymmetric conformation of 3 in a monoclinic crystal, space group P2(1) with a = 8.9608(4), b = 8.6348(5), c = 9.6468(4) A, beta = 96.139(4) degrees, V = 742.1(1) A3, Dc = 2.085 g cm-3, mu (MoK alpha) = 4.2 mm-1, and Z = 2. The structure was refined to R = 0.039 and Rw = 0.047 for 5181 observed reflections. The furanoid ring of 3 adopts an envelope E5 conformation slightly distorted towards 4T5, with puckering parameters psi = 313.49 degrees and q = 0.37 A. The asymmetric conformation is rationalized in terms of the weak packing forces in the crystal. PMID- 7780988 TI - Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. AB - Breast carcinomas are known to express platelet-derived growth factor (PDGF), a known connective tissue mitogen. In order to further evaluate the potential role of PDGF in these epithelial tumors, expression of the PDGF B chain (PDGF-B) and the PDGF receptor beta subunit (PDGFR) was analyzed by immunocytochemistry and in situ hybridization in 49 benign and malignant breast tissues. PDGF-B expression was analyzed with respect to the expression of the proliferating cell nuclear antigen, as well as tumor grade, p53 overexpression, estrogen receptor, progesterone receptor, and c-erbB-2 expression. Expression of PDGF-B protein and mRNA was restricted to the breast epithelium and tumor cells except for scattered tissue macrophages. A strong correlation was found between increasing proliferating cell nuclear antigen indices and PDGF-B expression in both nonmalignant (P = 0.01) and malignant (P = 0.02) breast specimens. Decreased PDGF B expression was found in postmenopausal atrophic breast tissue compared with normal breast tissue (P = 0.04). Within the subgroup of malignant tumors, no correlations were found between PDGF-B expression and tumor grade or p53 overexpression. In 16 of the malignant tumors evaluated for estrogen/progesterone receptor status and c-erbB-2 overexpression, no correlations with PDGF-B expression were found. Membranous PDGFR immunostaining was present within the fibroblastic cell population in all of the tissues examined but not in the nonmalignant breast epithelium. Six malignant specimens had detectable cytoplasmic expression of PDGFR. There was no correlation between this PDGFR expression and proliferating cell nuclear antigen indices, but a correlation was noted between increasing estrogen receptor expression and PDGFR cytoplasmic expression (P = 0.04). The results support a paracrine role for PDGF-B in malignant and benign breast epithelial cell proliferation. PMID- 7780990 TI - Solid-phase synthesis of a glycosylated hexapeptide of human sialophorin, using the trichloroacetimidate method. AB - A hexapeptide containing a beta-D-Gal p-(1-->3)-alpha-D-Gal pNAc-(1-->O)-L threonine unit was synthesized using glycosylated pentafluorophenyl esters in an Fmoc-based strategy. In all of the glycosylation reactions, trichloroacetimidates were successfully employed. The disaccharide moiety was prepared from tetra-O acetyl-alpha-D-galactopyranosyl trichloroacetimidate and tert-butyldimethylsilyl 2-azido-6-O-benzoyl-2-deoxy-beta-E-galactopyranoside with boron trifluoride etherate as a catalyst. The glycosylated active esters were obtained in the reaction of alpha and beta 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1-->3) 4-O-acetyl-2-azid o-6- O-benzoyl-2-deoxy-D-galactopyranosyl trichloroacetimidates with Fmoc-protected pentafluorophenyl esters of L-serine and L-threonine in the presence of trimethylsilyl trifluoromethanesulfonate as Lewis acid. The glycosylated pentafluorophenyl ester of L-threonine was transformed into glycopeptides via a solid-phase synthesis. Azide reduction and N-acetylation were performed on the solid phase with a thioacetic acid-pyridine mixture. The glycopeptide was then cleaved from the resin with strong acid, also removing the acid-labile protecting groups of the peptide chain. Finally, the acyl groups used for sugar protection were cleaved with sodium methoxide, affording the completely deprotected N-acetyl-L-leucyl-L-glutamyl-O-[beta-D-galactopyranosyl-(1-->3)-2- acetamido-2-deoxy-alpha-D-galactopyranosyl]-L-threonyl-L-seryl-L-threony l- glycinamide (1) in high purity. PMID- 7780991 TI - Stereoselective synthesis of a blood group A type glycopeptide present in human blood mucin. AB - N,N-Dimethyl-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1-->3)-O- [(alpha L-fucopyranosyl)-(1-->2)]-O-(beta-D-galactopyranosyl)-(1-->3)-O- (2-acetamido-2 deoxy-alpha-D-galactopyranosyl)-(1-->3)-L-serine, a core I glycotetraosyl peptide structure and a predominant substructure in complex glycan-glycoproteins present in human blood group A ovarian mucin, was synthesized for the first time. The title compound was synthetically accomplished via the following key manoeuvres: regio- and stereo-controlled construction of the alpha-GalNAc-(1-->3)-Gal synthon, stereoselective glycosylation generating a alpha-GalN3-(1-->3)-Ser glycopeptide synthon and alpha-selective fucosylation towards an acceptor which was derived from glycosylation of the latter two synthons. An alternative route to that of the latter, to synthesize a fully protected equivalent of the title compound, involving the coupling of a alpha-GalNAc-(1-->3)-beta-Gal-(1-->3) GalN3X synthon to an aglycon serine derivative, is described herein. PMID- 7780992 TI - Synthesis of N-beta-D-glucopyranosyluronate derivatives of barbital, phenobarbital, metharbital, and mephobarbital. AB - The synthesis and characterization of barbital, phenobarbital, metharbital, and mephobarbital glucuronides is reported. The condensation of per(trimethylsilyl) barbital and -phenobarbital with methyl 1,2,3,4-tetra-O-acetyl-beta-D glucopyranuronate in the presence of trimethylsilyl trifluoromethanesulfonate gave moderate yields of the N1-(beta-D-glucopyranosyluronate) barbiturate derivatives. The diastereomers of the phenobarbital derivatives were resolved by use of C18 reversed-phase HPLC. The homologous N3-methyl barbiturate N1 glucuronates were prepared by reaction of the barbital and phenobarbital N1 glucuronate derivatives with diazomethane. The absolute configuration of the phenobarbital N1-beta-D-glucopyranuronate epimers was determined by oxidative removal of the glycon from the mephobarbital N1-beta-D-glucopyranuronate epimers to give the optical isomers of mephobarbital. The spectroscopic data for this series of compounds will facilitate the characterization of N-glycosylated imide xenobiotics that may be detected as mammalian metabolites in biodisposition studies. PMID- 7780993 TI - Enzymic transfer of 6-modified D-galactosyl residues: synthesis of biantennary penta- and hepta-saccharides having two 6-deoxy-D-galactose residues at the nonreducing end and evaluation of 6-deoxy-D-galactosyl transfer to glycoprotein using bovine beta-(1-->4)-galactosyltransferase and UDP-6-deoxy-D-galactose. AB - UDP-6-Deoxy-D-galactose and UDP-6-deoxy-6-fluoro-D-galactose were synthesized and their transfer to 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine) by beta (1-->4)-galactosyltransferase was examined. The transfer rates of 6-deoxy-D galactose and 6-deoxy-6-fluoro-D-galactose were 1.3 and 0.2% of that of D galactosyl transfer, respectively. The 2-acetamido-4-O-(6-deoxy-beta-D galactopyranosyl)-2-deoxy-D-glucopyranose (6'-deoxy-N-acetyllactosamine) and methyl 2-acetamido-4-O-(6-deoxy-6-fluoro-beta-D-galactopyranosyl)-2-deoxy-D- glucopyranoside (6'-deoxy-6'-fluoro-N-acetyllactosamine) were synthesized enzymatically in 30 and 59% yields, respectively. Further, 6-deoxy-D-galactose could be completely transferred to N-linked type biantennary oligosaccharides having two N-acetyl-D-glucosaminyl residues at the nonreducing end to give the corresponding penta- and hepta-saccharides in 55 and 57% yields, respectively. An assay of 6-deoxy-D-galactosyl transfer using asialo agalacto alpha 1-acid glycoprotein as an acceptor suggested that 6-deoxy-D-galactose was transferred to about 30% of the N-acetyl-D-glucosaminyl residues in the N-linked oligosaccharides of the glycoprotein. PMID- 7780994 TI - The structure of the capsular polysaccharide of Escherichia coli O8:K43:H11. AB - The primary structure of the acidic capsular polysaccharide of Escherichia coli 08:K43:H11 was shown by monosaccharide analysis, methylation analysis, beta elimination, and by 1D and 2D 1H and 13C NMR spectroscopy to be composed of branched pentasaccharide repeating units with the structure. PMID- 7780995 TI - The structure of a novel polysaccharide produced by Bradyrhizobium species within soybean nodules. AB - Certain strains of Bradyrhizobium japonicum and B. elkanii produce a polysaccharide within the root nodules of their legume host, soybean. These nodule polysaccharides (NPSs) were isolated and characterized. The NPS produced by B. elkanii strains proved to be identical in glycosyl composition and linkages to the extracellular polysaccharide (EPS) of this species indicating that the NPS and EPS for B. elkanii have identical structures (W.F. Dudman, Carbohydr. Res., 66 (1978) 9-23), [formula: see text] However, the structure of the NPS from B. japonicum proved to be quite different from that of its EPS. Methylation analysis of this NPS showed that it consists of 3-linked Gal, 3-linked Rha, 2,4-linked Rha, 4-linked Rha, and terminal 2-O-methyl GlcA in a 1:1:1:1:1 ratio. Stereochemical configurations of the glycosyl residues were determined by the preparation and analysis of trimethylsilyl (Me3Si) (-)-2-butyl glycosides. NMR spectroscopy (both 1H and 13C) showed that the Gal residue is alpha-linked, while all the other glycosyl residues are beta-linked. Oligosaccharides produced by periodate oxidation-Smith degradation were purified, as were oligosaccharides produced by partial acid hydrolysis. Characterization of the Smith degradation products by methylation analysis. NMR spectroscopy, electrospray-mass spectrometry, and characterization of the partial acid hydrolysate oligosaccharides showed that the repeating oligosaccharide unit of the NPS has the structure, [formula: see text] PMID- 7780996 TI - NMR studies of acetan and the related bacterial polysaccharide, CR1/4, produced by a mutant strain of Acetobacter xylinum. AB - Acetan is a bacterial polysaccharide produced by Acetobacter xylinum NRRL B42. Chemical mutagenesis of A.xylinum allowed selection of a mutant strain which produced a new polysaccharide, CR1/4. 2D NMR methods have been used to assign the 1H and 13C spectra of the two polysaccharides and to determine that CR1/4 has the structure shown below. The total number of O-acetyl groups is slightly less than two per repeating unit. [formula: see text] The pentasaccharide side chain of acetan is truncated to a disaccharide unit in CR1/4, but the structures are otherwise identical. In particular, the degree of acetylation is about the same and the O-acetyl groups are located at the same position in both polysaccharides. PMID- 7780998 TI - [On the meaning of life and death, today]. PMID- 7780997 TI - The preparation of sucrose monophosphates from dried mixtures of sucrose and sodium phosphate. PMID- 7780999 TI - [The role of the cardiologist in the emergency department]. PMID- 7781000 TI - [Myocardial infarct with normal coronary vessels: an association with dysfunction of the coronary microcirculation]. AB - The association of acute myocardial infarction (AMI) with normal coronary arteries was analyzed prospectively. A series of 128 consecutive patients underwent coronary angiography within 1 week from AMI. Seven patients, all females, had no coronary artery lesions and were considered eligible for the study. All 7 patients underwent atrial pacing (10 g/min increments every 2 min), ergonovine testing (E; total dose 0.650 mg i.v.). Great cardiac vein flow (GCVF; thermodilution technique), mean aortic pressure (MAP), anterior coronary resistance (ACR) and myocardial lactate extraction [(Lac art-Lac gcv)/Lac art] were measured at baseline and during testing. Pacing-induced typical chest pain occurred in 5 patients: 4 of them showed concurrent significant (> or = 0.15 mV) ST downsloping. At peak pacing, GCVF increased only by < 50%, or even decreased, in all patients. Baseline lactate extraction (0.13 +/- 0.11) changed to lactate production (-0.15 +/- 0.10) in 7/7 patients. None of the patients showed focal epicardial coronary artery spasm following E. During testing, however, all 7 patients showed decrease in GCVF (110 +/- 47 versus 74 +/- 21; p < 0.005), increase in ACR (0.92 +/- 0.29 versus 1.43 +/- 0.20; p < 0.001), and significant coronary lactate production (-0.18 +/- 0.12). Six patients referred slight to moderate chest pain, which was accompanied by ST downsloping in 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781001 TI - [The noninvasive demonstration of functional reinnervation after heart transplantation]. AB - Although RR interval variability appears to be an ideal method for assessing reinnervation after heart transplantation, it has been shown that respiratory sinus arrhythmia is caused by the mechanical effect of respiration on the right atrium. The neck-suction induces heart rate changes only by means of nervous reflex and its hemodynamic effect is local and hence appears as a useful method for assessing reinnervation. We tested the presence of autonomic reinnervation in 18 heart transplant recipients, compared to 12 donor-age-matched controls. We measured the power of RR interval low- (LF, around 0.1 Hz) and respiratory fluctuations (HF) before and during rhythmic neck-suction stimulation at 0.1 Hz and at a frequency (0.20 Hz) similar to, but distinct from, that of respiration (controlled at 0.25 Hz), before and during 0.04 mg/kg atropine infusion, using autoregressive spectral analysis of RR interval, respiration and neck pressure signals. The relationship between pairs of signals at each frequency was quantitatively assessed by bivariate coherence function. All transplanted subjects showed low-amplitude HF, related to respiration. Detectable LF (whose power was lower than in controls: 1.15 +/- 0.39 versus 6.08 +/- 0.27 1n-ms2, p < 0.001), non coherent with respiration, were present in 11/18 transplanted subjects, and correlated with months since transplantation (r = +0.59, p < 0.05). HF neck suction induced the presence of a 0.20 Hz fluctuation in 12/12 controls, distinct from and greater than the 0.25 Hz respiratory component (7.28 +/- 0.26 versus 6.69 +/- 0.74 1n-ms2, p < 0.01); this was not seen in any of the transplanted subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781003 TI - [Recent large studies of the elderly hypertensive: results and indications]. PMID- 7781002 TI - [Gene therapy for the treatment of restenosis after coronary angioplasty]. AB - Accumulation and proliferation of vascular smooth muscle cells are associated with atherosclerosis and hypertension. Proliferation of smooth muscle cells constitutes a major pathological event responsible for long-term failure of coronary and peripheral arterial bypass graft as well as the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The incidence of restenosis after PTCA has been reported to be as high as 40-45% within 3-6 months. Major advantages in recombinant deoxyribonucleic acid (DNA) technology and eukaryotic gene regulation allow to hypothesize gene therapy as a potential treatment for inherited and acquired diseases. Gene therapy is the introduction of genes into somatic cells to correct an inherited or acquired disorder through the synthesis of missing or defective protein. Although no disease has yet been treated by gene therapy, several gene transfer protocols have recently been undertaken. We have studied the expression of foreign DNA that has been introduced into smooth muscle cells after balloon carotid injury in a rat model of angioplasty. The effects of different degree of balloon injury on neointima formation and c-fos expression was also assessed. Our data demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of restenosis after PTCA. PMID- 7781004 TI - [Mental stress and cardiopathies]. PMID- 7781005 TI - Severe calcific pulmonic valve stenosis and restrictive ventricular septal defect in a 64-year-old man. Results of percutaneous double balloon valvuloplasty. AB - The clinical and hemodynamic features of a 64-year-old symptomatic man with severe calcific pulmonic valve stenosis and restrictive ventricular septal defect are reported. Successful double balloon percutaneous pulmonic valvuloplasty immediately produced excellent symptomatic benefit and introduced expected and well tolerated hemodynamic changes. The transpulmonic valve peak systolic pressure gradient was reduced from 130 to 30 mmHg and pulmonary artery pressure increased to top normal levels acquiring normal pulse wave configuration. A left to-right shunt, negligible prior to valvuloplasty, increased appreciably producing a pulmonary to systemic flow ratio of 1.7. Reevaluation at 5 months revealed sustained hemodynamic profile. Symptomatic benefit and tolerance to ordinary physical activities have remained excellent at 1 year follow-up. PMID- 7781006 TI - Lipoprotein oxidation as a mediator of atherogenesis: insights from pharmacological studies. PMID- 7781007 TI - Neurocardiology update: role of the nervous system in coronary vasomotion. PMID- 7781008 TI - Stroma and the search for common ground. Plumbism or promiscuity? PMID- 7781009 TI - Abnormal ATP turnover in rat leg muscle during exercise and recovery following myocardial infarction. AB - OBJECTIVE: Clinical and animal studies show increased acidification of skeletal muscle during exercise in heart failure, implying increased anaerobic metabolism, and impaired recovery from exercise, implying defective oxidative function. This study aimed to define the quantitative relationship between these changes in exercise and recovery and relate skeletal muscle bioenergetics to cardiovascular function. METHODS: Wistar rats were studied four weeks after myocardial infarction or a sham operation. 31P magnetic resonance spectroscopy of the hind leg muscle was used to estimate rates of oxidative and non-oxidative ATP synthesis from changes in pH and phosphocreatine concentration during sciatic nerve stimulation and to estimate the maximum rate of mitochondrial ATP synthesis from the kinetics of phosphocreatine recovery after stimulation. RESULTS: Following myocardial infarction, cardiac function was abnormal, with evidence of left ventricular hypertrophy, failure, and diminished arterial pressure. There was impaired phosphocreatine recovery, suggesting an approximate halving of the maximum rate of mitochondrial ATP synthesis. CONCLUSIONS: The response to exercise of the infarct group was abnormal and was quantitatively consistent with the reduced maximum rate of mitochondrial ATP synthesis inferred from recovery, the oxidative deficit during exercise being made up by increased glycogenolysis, causing sufficient acidification to prevent an appropriate increase in [ADP]. PMID- 7781010 TI - Differential effects of lignocaine and hypercalcaemia on anisotropic conduction and reentry in the ischaemically damaged canine ventricle. AB - OBJECTIVE: Anisotropic conduction characteristics, which may be expressed as the ratio of conduction velocities in the longitudinal (Vlong) and transverse (Vtrans) fibre directions, have been shown to stabilise reentry and favour the induction of sustained, uniform ventricular tachycardia. The aim of this study was to investigate whether interventions affecting either excitability (lignocaine) or both excitability and cell coupling (hypercalcaemia) might produce differential effects on the Vlong/Vtrans ratio, and whether an intervention reducing this ratio might prevent the induction of sustained reentrant ventricular tachycardia. METHODS: The effects of hypercalcaemia [8.2(SD 3.8) mmol.litre-1] and lignocaine infusion [to 24.4(19) and 42.3(29) mumol.litre 1] on Vlong and Vtrans were determined from 127 electrograms recorded with a plaque electrode on the anterior left ventricular wall of healthy dogs or 3 d after occlusion of the left anterior descending coronary artery. Vlong and Vtrans were computed from isochronal maps displaying ellipsoid patterns with a long axis corresponding to longitudinal conduction and a short axis corresponding to transverse conduction, as determined during basic (S1) and premature (S2) stimulation from the centre of the plaque electrode. Infarcted heart preparations were subjected to programmed stimulation for induction of reentrant ventricular tachycardias. RESULTS: Hypercalcaemia reduced both Vlong and Vtrans (P < 0.05) but did not modify either the Vlong/Vtrans ratio or the induction and patterns of ventricular tachycardias. Lignocaine reduced Vlong and the Vlong/Vtrans ratio during premature stimulation (S2) of infarcted heart preparations (P < 0.05) and stabilised reentrant ventricular tachycardias in preparations in which only nonsustained, multiform ventricular tachycardias were induced under control conditions. CONCLUSIONS: Conduction velocities in the longitudinal and transverse directions can be differentially affected by selected pharmacological interventions, but the Vlong/Vtrans ratio is not a representative index of the facilitating influence of tissue anisotropy on reentry. Therefore, the role of anisotropy in this model of reentry is not confined to establishing disparity of a functional character between conduction velocities in the longitudinal and transverse directions. PMID- 7781011 TI - L-carnitine increases glucose metabolism and mechanical function following ischaemia in diabetic rat heart. AB - OBJECTIVE: Stimulation of glucose oxidation by L-carnitine improves mechanical recovery of ischaemic hearts from non-diabetic rats perfused with high levels of fatty acids. The aim of this study was to determine whether L-carnitine also increases glucose oxidation and function in diabetic rat hearts, which have suppressed glucose metabolism. METHODS: Isolated working hearts from six week streptozotocin diabetic and control rats were perfused with 11 mM (5-3H/U-14C) glucose, 1.2 mM palmitate. Hearts were paced at 260 beats.min-1 during 60 min of low flow ischaemia, and were then subjected to 30 min of aerobic reperfusion. Total myocardial carnitine content in these hearts was first increased by a 60 min aerobic perfusion with 10 mM L-carnitine. RESULTS: Steady state glucose oxidation rates (measured as 14CO2 production) were depressed in diabetic rat hearts compared to control hearts during the initial aerobic period. However, L carnitine treatment dramatically increased glucose oxidation rates in the diabetic rat hearts, as well as in control hearts. Glycolysis was also lower in diabetic rat hearts compared to control hearts, although L-carnitine treatment significantly increased glycolysis only in the diabetic animals. During reperfusion, steady state rates of glucose oxidation and glycolysis returned to preischaemic values in both the control and diabetic groups. L-carnitine treatment stimulated glucose oxidation during reperfusion in control and diabetic rat hearts. Mechanical function of control hearts returned to 38(SEM 9)% of preischaemic values, whereas in L-carnitine treated hearts function returned to 90(7)% of preischaemic values. Recovery of function was 80(15)% of preischaemic in the diabetic rat hearts, and was increased to 100% of preischaemic function with L-carnitine. CONCLUSIONS: Carnitine improves recovery of function of ischaemic non-diabetic rats by stimulating glucose oxidation during reperfusion, whereas it may be beneficial in diabetic rat hearts by stimulating both glycolysis during ischaemia and glucose oxidation during reperfusion. PMID- 7781012 TI - Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat. AB - OBJECTIVE: The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event. METHODS: Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt. RESULTS: Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals. CONCLUSION: Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity. PMID- 7781013 TI - Effects of inorganic phosphate and ADP on calcium handling by the sarcoplasmic reticulum in rat skinned cardiac muscles. AB - OBJECTIVE: The aim was to investigate whether, and how, increases in inorganic phosphate (Pi) and ADP, similar to those occurring intracellularly during early myocardial ischaemia, affect the calcium handling of the sarcoplasmic reticulum. METHODS: Rat ventricular trabeculae were permeabilised with saponin. The physiological process of calcium induced calcium release (CICR) from the muscle sarcoplasmic reticulum was triggered via flash photolysis of the "caged Ca2+", nitr-5. Alternatively, calcium release was induced by rapid application of caffeine to give an estimate of sarcoplasmic reticular calcium loading. The initial rate of sarcoplasmic reticular calcium pumping was also assessed by photolysis of caged ATP at saturating [Ca2+]. Myoplasmic [Ca2+] (using fluo-3) and isometric force were measured. RESULTS: Pi (2-20 mM) significantly depressed the magnitude of CICR and the associated force transient. Sarcoplasmic reticular calcium loading was inhibited even more than CICR by Pi, suggesting that reduced calcium loading could account for all of the inhibitory effect of Pi on CICR and that Pi may slightly activate the calcium release mechanism. The reduced sarcoplasmic reticular calcium loading seemed to be due to a fall in the free energy of ATP hydrolysis (delta GATP) available for the calcium pump, since equal decreases in delta GATP produced by adding both Pi and ADP in various ratios caused similar falls in the calcium loading of the sarcoplasmic reticulum. The caged ATP experiments indicated that Pi (20 mM) did not affect the rate constant of sarcoplasmic reticular calcium uptake. ADP (10 mM) alone, or with 1 mM Pi, inhibited calcium loading. In spite of this, ADP (10 mM) did not alter CICR and, when 1 mM Pi was added, ADP increased CICR above control. CONCLUSIONS: An increase in intracellular Pi reduces sarcoplasmic reticular calcium loading and thus depresses the CICR. This could be an important contributing factor in the hypoxic or ischaemic contractile failure of the myocardium. However the detrimental effect of Pi may be offset to some extent by a stimulatory action of ADP on the calcium release mechanism of CICR. PMID- 7781014 TI - Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart. AB - OBJECTIVE: The aim was (1) to clarify whether alpha adrenoceptor and adenosine receptor stimulation is involved in the anti-infarct effect of ischaemic preconditioning in the rat heart, and (2) to test the hypothesis that signal transduction through membrane bound protein kinase C is essential for the protection. METHODS: Isolated, buffer perfused rat hearts were subjected to 30 min of regional ischaemia and 120 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by staining with triphenyltetrazolium chloride. RESULTS: Ischaemic preconditioning with three cycles of 5 min ischaemia plus 5 min of reperfusion significantly reduced infarct size as compared to non-preconditioned group [4.5(SEM 0.6)% of the risk zone v 45.5(5.7)%, P < 0.001]. Blockade of alpha adrenoceptors alone and simultaneous blockade of alpha adrenoceptors with phenoxybenzamine (10 microM) and adenosine receptors with sulphophenyltheophylline (100 microM) did not prevent the protective effect of ischaemic preconditioning [infarct size = 2.4(0.4) and 5.6(1.9)% respectively, NS v the non-treated preconditioned group]. Blocking either the membrane binding of protein kinase C with polymyxin B (1 microM) or direct inhibition of protein kinase C activity with chelerythrine (2 microM) completely abolished the infarct size reducing effect of ischaemic preconditioning [32.4(3.3)% and 48.2(4.0)% respectively, P < 0.005 v non-treated preconditioned group: NS v the non-preconditioned group]. CONCLUSIONS: In the rat heart infarct model the protective effect of ischaemic preconditioning is not mediated through stimulation of alpha adrenoceptors alone or the combined stimulation of alpha adrenergic and adenosine receptors, and it is dependent on activation of membrane bound protein kinase C. PMID- 7781016 TI - Effect of intraluminal application of tissue-type plasminogen activator on the fibrinolytic activity of experimental vein grafts. AB - OBJECTIVE: The aim was to quantify the effect of intraluminally applied tissue type plasminogen activator (tPA) on the fibrinolytic activity of experimental vein grafts and assess the effect of pretreatment of the vein on early platelet and thrombus formation using histological techniques. METHODS: A pig model of bilateral saphenous venin-carotid artery grafts was used. In each animal one side of the neck was grafted using vein distended to 230 mm Hg and pretreated with tPA (1 mg.ml-1) for a period of 15 min before grafting (treated graft). The perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activity were quantified using fibrin plate techniques and specific chromogenic assays for tPA and urokinase (uPA) in tissue extract (n = 6 animals). Histological assessment was made using light and scanning microscopy (n = 4 animals). RESULTS: Surgical preparation and distention significantly reduced the fibrinolytic activity of pig saphenous vein in terms of areas of lysis produced on fibrin plates (P < 0.05), tPA activity (P < 0.05), and uPA activity (P < 0.05). Pretreatment of distended vein with tPA before grafting significantly enhanced its fibrinolytic activity after 2 h perfusion compared to control (untreated) grafts, as assessed by areas of lysis on fibrin plates (P < 0.05) and specific tPA activity (P < 0.05). Treated grafts also showed qualitatively less platelet and thrombus formation on histological examination. CONCLUSIONS: Pretreatment of surgically harvested vein by intraluminal application of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further investigation to validate its potential as a means of providing local anticoagulation to veins implanted as arterial grafts thereby reducing the incidence of early graft thrombosis. PMID- 7781015 TI - Central vasopressin in experimental aortic stenosis in the rat. AB - OBJECTIVE: In several forms of heart disease characterised by low cardiac output, activated neurohumoral systems including increased vasopressin plasma levels play a key role in the changes in cardiovascular function. The aim of this study was to test the hypothesis that under such conditions the central vasopressin system might also be altered, which could contribute to deranged cardiovascular control. METHODS: Aortic stenosis was produced in 22 rats by placing a Silver clip (inner diameter 0.6 mm) on the ascending aorta. After 12 weeks, haemodynamic and hormonal measurements were performed, and vasopressin content was determined in 20 microdissected brain areas (micropunch technique). Twenty two sham operated rats served as controls. RESULTS: Twelve weeks after placing the supravalvular clip, significant aortic stenosis was documented by left ventricular myocardial hypertrophy. Cardiac index was significantly reduced and the peripheral vascular resistance index was increased, while poststenotic aortic pressure was non significantly decreased. Plasma renin concentration [6.8(SEM 0.9) v 2.1(0.2) ngAI.ml-1.h-1 in controls] and plasma vasopressin [32.9(12.5) v 18.4(6.0) pg.ml 1] were significantly increased, while plasma and urinary noradrenaline remained unaltered. The vasopressin content was significantly altered in eight out of 20 brain areas investigated. Concerning the vasopressin producing hypothalamic nuclei, concentrations were increased in the paraventricular [7494(360) v 4744(237) pg.mg-1 protein, P < 0.05] and suprachiasmatic [3613(170) v 1784(197) pg.mg-1 protein, P < 0.01], but not in the supraoptic nuclei. Rats with aortic stenosis showed significantly raised vasopressin concentrations in the median eminence [25 186(1682) v 37 367(1345) pg.mg-1 protein, P < 0.01], where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Vasopressin content was significantly decreased in locus coeruleus [49(5) v 89(6) pg.mg-1 protein], which is known to be involved in modulation of sympathetic activity. CONCLUSIONS: As well as showing increased secretion of vasopressin into the blood with consecutive peripheral antidiuretic and vasoconstrictive effects, these data suggest an alteration in the central vasopressin system in aortic stenosis which might transmit cardiovascular effects by neuromodulation and neuroregulation. PMID- 7781017 TI - Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency. AB - OBJECTIVE: Oxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data. METHODS: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary artery and 30 min reperfusion, segment shortening, the slope of end systolic pressure segment length relationship (Ees), external work (EW, derived from the area inside the left ventricular pressure segment length loop), the efficiency of energy conversion (EET, = EW/PLA x 100%, where PLA = total pressure-segment length area), mechanical efficiency (EW/MVO2), and their dependency on left ventricular end systolic pressure (Pes) were determined before and after induction of stunning, and during subsequent inotropic stimulation with dobutamine (1 and 3 micrograms.kg-1.min-1 over 15 min). RESULTS: The stunning protocol not only caused significant decreases in segment shortening, external work, energy conversion efficiency, and EW/MVO2 but also increased the afterload dependency of these variables. Before stunning an increase in Pes from 100 to 160 mm Hg decreased segment shortening from 18(SEM 1)% to 14(2)% (P > 0.05) and increased external work from 206(18) to 254(32) mm Hg.mm (P < 0.05). After induction of stunning the same increase in Pes caused a decrease in segment shortening from 9.5(1.8)% to -4.6(2.1)% (P < 0.05) and in external work from 149(21) to -11(10) mm Hg.mm (P < 0.05). The afterload dependency of the PLA was not altered by stunning, but the afterload dependency of energy conversion efficiency increased, since efficiency decreased from 67(3)% to 59(5)% as Pes was increased from 100 to 160 mm Hg before stunning, but from 57(5) to -7(5)% after induction of stunning (P < 0.05). Furthermore, the same increase in Pes resulted in an 8% decrease of EW/MVO2 before stunning and 107% after induction of stunning. Infusion of dobutamine not only restored segment shortening, external work, energy conversion efficiency, and EW/MVO2 of the stunned myocardium, but also attenuated their afterload dependency to pre stunning levels. CONCLUSIONS: Myocardial stunning increases the afterload dependency of segment shortening, external work, energy conversion efficiency, and mechanical efficiency, which can be attenuated by inotropic stimulation with dobutamine. However, the decrease in left ventricular end systolic pressure, which accompanies the induction of stunning, counteracts the decrease in these variables. These two mechanisms can explain most of the reported scatter in mechanical efficiency. PMID- 7781018 TI - Increased intracellular magnesium contributes to impairment of postischaemic cardiac function. PMID- 7781019 TI - High magnesium improves the postischaemic recovery of cardiac function. PMID- 7781020 TI - Differential expression of type 2 and type 3 inositol 1,4,5-trisphosphate receptor mRNAs in various mouse tissues: in situ hybridization study. AB - The inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel responsible for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned, and their genes have been classified into a family. The gene for the type 1 receptor (IP3R1) is predominantly expressed in cerebellar Purkinje neurons, but its gene product is localized widely in a variety of tissues; however, there is little information on what types of cells express the other two receptor types, type 2 and type 3 (IP3R2 and IP3R3, respectively). We studied the expression of the IP3R gene family in various mouse tissues by in situ hybridization histochemistry. Compared with IP3R1, the levels of expression of IP3R2 and IP3R3 mRNAs were low in all of the tissues tested. IP3R2 mRNA was localized in the intralobular duct cells of the submandibular gland, the urinary tubule cells of the kidney, the epithelial cells of epididymal ducts and the follicular granulosa cells of the ovary, while the IP3R3 mRNA was distributed in gastric cells, salivary and pancreatic acinar cells and the epithelium of the small intestine. All of these cells which express either IP3R2 or IP3R3 mRNA are known to have a secretory function in which IP3/Ca2+ signalling has been shown to be involved, and thus either IP3R2 or IP3R3 may be a prerequisite to secretion in these cells. PMID- 7781021 TI - Resolution of sensory and mucoid glycoconjugates with terminal alpha-galactose residues in the mucomicrovillar complex of the vomeronasal sensory epithelium by dual confocal laser scanning microscopy. AB - The organization of the mucomicrovillar complex of the vomeronasal sensory epithelium of adult rats was examined using confocal laser scanning microscopy. In specimens labeled with the FITC-conjugated isolectin B4 of Bandeiraea simplicifolia, which recognizes terminal alpha-galactose sugar residues of glycoconjugates, we demonstrated that the mucomicrovillar complex was composed of islet-like structures with a high-density alpha-galactose core. The mucomicrovillar complex was further resolved into sensory and mucoid components in double-labeling and dual scanning experiments. The sensory component, which consists of the dendritic terminals of olfactory marker protein-immunoreactive vomeronasal receptor neurons, contained cytosolic glycoconjugates with terminal alpha-galactose sugar residues. The extracellular mucoid component consisted of glycoconjugates containing terminal alpha-galactose derived from the glands associated with the vomeronasal organ. These results demonstrated the complex microchemical organization of the sensory and mucoid components of the mucomicrovillar complex. PMID- 7781022 TI - Experimental analyses of the rearrangement of ectodermal cells during gastrulation and neurulation in avian embryos. AB - The rearrangement of ectodermal cells was studied in chimeras in which grafts were transplanted during late gastrula and early neurula stages to heterotopic locations in avian embryos. Three types of experiments were done. In all experiments, Hensen's node was extirpated completely and replaced with an epithelial plug derived from 1 of 3 regions of the prospective ectoderm. In type 1 experiments, Hensen's node was replaced with a plug consisting of precursor cells of the floor plate of the neural tube. In type-2 experiments, Hensen's node was replaced with a plug consisting of precursor cells of the lateral wall of the neural tube. In type-3 experiments, Hensen's node was replaced with a plug consisting of precursor cells of the epidermal ectoderm. In all experiments, the amount and direction of cell rearrangement that occurred in the transplanted ectodermal plug was essentially typical for prospective ectodermal cells normally residing within Hensen's node. That is, transplanted ectodermal cells underwent lateral-to-medial cell-cell intercalation and contributed to the ventral midline of the neural tube along its entire rostrocaudal extent. In most embryos, a notochord was reconstituted from host cells, despite the fact that Hensen's node- the prime source of prospective notochordal cells in intact embryos--was extirpated completely; however, a few embryos had long notochordal gaps. In such essentially notochordless embryos, the ventral midline of the neural tube still derived from grafted cells, but it failed to form a floor plate, providing further confirmation of the results of several previous studies that the notochord is required to induce the floor plate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781023 TI - Immunocytochemical localization of ribonuclease in yolk granules of adult Rana catesbeiana oocytes. AB - To determine the localization of the pyrimidine-guanine sequence-specific ribonuclease in Rana catesbeiana (bullfrog) oocytes, the RNase was first isolated and used to prepare a specific rabbit antiserum. Only one protein of similar molecular size to the RNase was immunoprecipitated from ovary homogenate by the antiserum, but two bands were observed by Western blotting analysis. These two proteins were shown by further purification of antibody and Western blotting analysis to have similar antigenicity. Immunoprecipitation and Western blotting of tissue homogenates showed that the RNase was found predominantly in the ovary, but not in other tissues. The specific localization of the RNase was determined by immuno-electron microscopy of oocyte sections incubated with the specific antiserum; the yolk granules, but not other organelles, were found to contain the RNase. Most of the RNase was evenly distributed in the lateral amorphous area of the yolk granule but not in the central yolk crystal area which contains stored vitellogenin proteins. Our results indicate that the RNase is compartmentalized in the yolk granules of oocytes, which might prevent damage to cellular RNAs. PMID- 7781024 TI - Localization and coexistence of atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) in vertebrate adrenal chromaffin cells immunoreactive to TH, DBH and PNMT. AB - Antisera specific for mammalian atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) were applied to examine, in immunofluorescence, the occurrence of cells immunoreactive to ANP and NPY in the adrenal organs of mammals, birds, reptiles, amphibians, and bony fish. Catecholamine-containing cells were identified using antisera against tyrosine-hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. In all vertebrates studied, immunoreactivities to ANP and NPY occurred in adrenal chromaffin cells but were absent from the cortex or its homolog, the interrenal. The majority of immunoreactivities to ANP and NPY was confined to the adrenaline cells. In mammals, the number of ANP-immuno-reactive cells (60%-80% of the total cell population) exceeded that of the NPY-immunoreactive cells (35%-45%). In birds, reptiles, and Amphibia, the numbers of ANP-immunoreactive (35%-40%) and NPY immunoreactive (30%-35%) cells were in a similar range. The bony fish showed a density of both ANP-immunoreactive (80%-90%) and NPY-immunoreactive (35%-40%) cells. In all species studied, immunoreactivities to ANP and NPY partially coexisted. Generally, 30%-55% of the ANP-immunoreactive cells also contained NPY immunoreactivity. In rat, coexistence amounted to almost 100% and in quail to 95%. Except for the rat, three subpopulations of chromaffin cells seemed to occur: ANP-immunoreactive non-NPY-immunoreactive, ANP-immunoreactive+NPY immunoreactive, and NPY-immunoreactive non-ANP-immunoreactive cells. Thus, adrenal ANP and NPY share a conservative history and coexist as early as at the level of bony fish. The endocrine actions of ANP and NPY derived from medullary cells on cortical cells as found in mammals might be based on an ancestoral paracrine system. In submammalians, ANP and NPY may not only act as endocrine hormones, but also influence steroid-producing interrenal cells in a paracrine manner, and act as modulators on chromaffin cells. PMID- 7781025 TI - Retarded myogenic cell replication in regenerating skeletal muscles of old mice: an autoradiographic study in young and old BALBc and SJL/J mice. AB - The patterns of skeletal muscle precursor cell replication after crush injury were compared by the use of autoradiographic techniques, in young (4-week-old) and old (39-week-old) BALBc and SJL/J mice. Similar comparisons were made between cut and crush lesions in old BALBc muscle. Muscle precursor cell replication commenced at 18-24 h after injury in both young and old muscles from both strains of mice. In young BALBc muscle the peak of myogenic activity at 60 h was 36 h earlier than in old mice. SJL/J muscle responded more rapidly than did BALBc: in young SJL/J the peak myogenic activity was at 46 h (14 h earlier than in young BALBc muscle), and in old SJL/J muscle the peak activity at 72 h was 24 h earlier than in old BALBc muscle. In all mice (both young and old) myogenic cell replication was substantially reduced by 120 h after injury. A comparison of the timing of muscle precursor cell replication in cut and crush lesions in old BALBc mice revealed a more rapid response in the cut lesion; this difference between the lesions is comparable with data from identical lesions in 6-8-week-old BALBc mice (McGeachie and Grounds 1987). However, the peak of myogenic replication in the older mice in the present study was some 26-36 h later than in the younger 6 8-week-old mice. These experiments show that, whilst muscle precursor cell replication commences at approximately the same time (about 24 h) after injury in young and old mice, the peak level of activity is delayed by some 24-36 h in old mice. In addition, the SJL/J mouse strain responds more rapidly and prolifically to muscle injury than does the BALBc strain. PMID- 7781026 TI - The expression of the gene coding for parathyroid hormone-related protein (PTHrP) during tooth development in the rat. AB - By means of in situ hybridisation studies, it is shown that parathyroid hormone related protein (PTHrP) mRNA is strongly expressed in the developing enamel organs of rat teeth. In particular, the cervical loop hybridises strongly with the PTHrP probe and expression is maintained at this site throughout life in the permanently erupting incisor teeth. In mature molar teeth, expression is downregulated to low levels and confined to the epithelial cell rests of Malassez and/or cementoblasts which may derive from these. The gene is also expressed at low levels in the tissue overlying the erupting molars and, thereafter, in the junctional epithelia and connective tissue cells of the epithelial attachment on all tooth surfaces. The premise that PTHrP may undergo post-translational processing and that the resultant products could act in different ways raises the possibility of its exerting multiple paracrine actions during tooth development. These could include the control of cell division and local vascular dilation during development. PMID- 7781027 TI - Colocalization of neuropeptides and NADPH-diaphorase in the intra-adrenal neuronal cell bodies and fibres of the rat. AB - Colocalization of vasoactive intestinal peptide, neuropeptide Y, calcitonin gene related peptide, substance P, and tyrosine hydroxylase, respectively, with NADPH diaphorase staining in rat adrenal gland was investigated using the double labelling technique. All vasoactive intestinal peptide- and some neuropeptide Y immunoreactive intrinsic neuronal cell bodies seen in the gland were double stained with NADPH-diaphorase. Double labelling also occurred in some nerve fibres immunoreactive to vasoactive intestinal peptide and neuropeptide Y in the medulla and cortex. No colocalization of calcitonin gene-related peptide, substance P or tyrosine hydroxylase immunoreactivity with NADPH-diaphorase staining was observed. However, nerve fibres with varicosities immunoreactive for all the neuropeptides examined were closely associated with some of the NADPH diaphorase-stained neuronal cell bodies. Thus, in rat adrenal gland, nitric oxide is synthesized in all ganglion cells containing vasoactive intestinal peptide and in some containing neuropeptide Y, but not in those containing calcitonin gene related peptide, substance P or tyrosine hydroxylase. PMID- 7781028 TI - Distribution of immunoreactive neuropeptides in the pancreas of the bullfrog, Rana catesbeiana, demonstrated by immunofluorescence. AB - Indirect double immunofluorescence labelling for eight neuropeptides in the pancreas of the bullfrog, Rana catesbeiana, demonstrated the occurrence, distribution, and coexistence of certain neuropeptides in the exocrine and endocrine pancreas. Immunoreactivity of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), FMRFamide (FMRF), and galanin (GAL) was localized in nerve fibers distributed between the acini and around the duct system and vasculature of the exocrine pancreas. In these regions, CGRP-immunoreactive fibers were more numerous than those containing the other five peptides. Almost all SP fibers showed coexistence of SP with CGRP, and about one third of fibers also showed coexistence of SP with VIP, NPY, FMRF, and GAL. In the endocrine pancreas, SP, CGRP, VIP, and GAL were recognized in the nerve fibers around and within the islets of Langerhans, and VIP and GAL fibers were more numerous than SP and CGRP fibers. All CGRP fibers, and about half of the VIP and GAL fibers were immunoreactive for SP. NPY- and FMRF-immunoreactive cells were found at the periphery of the islets. These findings suggest that the exocrine and endocrine pancreatic functions of the bullfrog are under the control of peptidergic innervation. PMID- 7781029 TI - Structural organization and epithelial cells types of the intestinal diverticula (protopancreas) of ammocoetes of southern hemisphere lampreys: functional and phylogenetic implications. AB - Larvae of the two southern hemisphere lamprey genera, Mordacia and Geotria, possess one and two intestinal diverticula, respectively, each originating at the oesophageal-intestinal junction. These diverticula comprise an inner layer of simple columnar epithelium composed solely of zymogen and mucous cells, a middle layer consisting mainly of a blood sinus, and an outer serosa layer covered by a simple squamous epithelium (mesothelium). The inner surface is highly folded only in Mordacia. The secretion of mucus probably protects the epithelium from the effects of digestive enzymes secreted by the zymogen cells and/or bile, which enters the diverticulum at its tip. Unlike the situation in southern hemisphere lampreys, the zymogen cells of the larvae of holarctic lampreys are located in the anterior intestine, a condition considered to be "primitive". It is thus proposed that intestinal diverticula were developed during the evolution of southern hemisphere lampreys. The relocation of zymogen cells in the diverticula increases the area for these cells, and thus the capacity for the synthesis and secretion of digestive enzymes, particularly in Mordacia where the inner surface is folded. PMID- 7781030 TI - GABA and glutamate-like immunoreactivity at synapses received by dorsal unpaired median neurones in the abdominal nerve cord of the locust. AB - Dorsal unpaired median (DUM) neurones in the abdominal ganglia of the locust were impaled with microelectrodes and some were injected intracellularly with horseradish peroxidase so that their synapses could be identified in the electron microscope. Simultaneous recordings from DUM neurones in different abdominal ganglia revealed that they received common postsynaptic potentials from descending interneurones. Post-embedding immunocytochemistry using antibodies against GABA and glutamate was carried out on ganglia containing HRP-stained neurones. GABA-like immunoreactivity was found in 39% (n = 82) of processes presynaptic to abdominal DUM neurones and glutamate-like immunoreactivity in 21% (n = 42) of presynaptic processes. Output synapses from the DUM neurites were rarely observed within the neuropile. Structures resembling presynaptic dense bars but not associated with synaptic vesicles, were seen in some large diameter neurites. PMID- 7781031 TI - Distribution of catch-relaxing peptide (CARP)-like immunoreactive neurons in the central and peripheral nervous system of Helix pomatia. AB - Immunocytochemistry was performed on the nervous system of Helix by the use of an antibody raised against a myotropic neuropeptide, the catch-relaxing peptide (CARP), isolated from Mytilus edulis. In each ganglion of the central nervous system of Helix pomatia, numerous CARP-immunoreactive cell bodies and a dense immunoreactive fiber system could be observed with a dominancy in the cerebral and pedal ganglia. The majority of the immunoreactive neurons are unipolar, although multipolar neurons also occur. In the neuropil areas, CARP immunoreactive fibers show extensive arborization, which may indicate a central role of CARP. CARP-immunoreactive elements could be observed in each investigated peripheral nerve and peripheral areas, namely in the intestine, heart, aorta, buccal mass, lips, and foot. However, CARP-immunoreactive cell bodies could only be demonstrated in the intestine and the foot musculature. Thin varicose CARP immunoreactive fibers were observed over both muscle and gland cells in the different peripheral organs, suggesting a peripheral role of CARP. In vivo CARP injection into the body cavity (10(-3), 10(-4), 10(-5) M) altered the general behavioral state of the animals and induced the relaxation of the musculature of the whole body wall indicating that CARP has a significant role in the regulation of muscle contraction. PMID- 7781032 TI - Areas of asbestoid (amianthoid) fibers in human thyroid cartilage characterized by immunolocalization of collagen types I, II, IX, XI and X. AB - The distribution of type I, II, IX, XI and X collagens in and close to areas of asbestoid (amianthoid) fibers in thyroid cartilages of various ages was investigated in this study. Asbestoid fibers were first detected in thyroid cartilage from a 3-year-old male child. Areas of asbestoid fibers functionally appear to serve as guide rails for vascularization of thyroid cartilage. Alcian blue staining in the presence of 0.3 M MgCl2 revealed a loss of glycosaminoglycans in areas of asbestoid fibers. In addition, the fibers reacted positively with antibodies against collagen types II, IX and XI, but showed no staining with antibodies to collagen types I and X. Territorial matrix of adjacent chondrocytes showed the same staining pattern. In addition to staining for type II, IX and XI collagens, asbestoid fibers showed strong immunostaining for type I collagen after puberty but not for type X collagen. However, groups of chondrocytes within areas of asbestoid fibers reacted strongly with antibodies to type X collagen, suggesting that this collagen plays an important role in matrix of highly differentiated chondrocytes. The finding that these type X collagen positive chondrocytes also revealed immunostaining for type I collagen confirms previous studies showing that hypertrophic chondrocytes can further differentiate into cells that are characterized by the synthesis of type X and I collagens. PMID- 7781033 TI - Leu-callatostatin gene expression in the blowflies Calliphora vomitoria and Lucilia cuprina studied by in situ hybridisation: comparison with Leu callatostatin confocal laser scanning immunocytochemistry. AB - In situ hybridisation studies using a digoxigenin-labelled DNA probe encoding the Leu-callatostatin prohormone of the blowflies Calliphora vomitoria and Lucilia cuprina have revealed a variety of neurones in the brain and thoracico-abdominal ganglion, peripheral neurosecretory neurones, and endocrine cells of the midgut. With two exceptions, the hybridising cells are the same as those previously identified in immunocytochemical studies of sections and whole-mounts using Leu callatostatin COOH-terminal-specific antisera. Within the brain and suboesophageal ganglion, there is a variety of neurones ranging from a single pair of large cells situated in the dorsal protocerebrum, to the several pairs of neurones in the tritocerebrum, some of which, in immunocytochemical preparations, can be seen to project via axons in the cervical connective to the thoracico abdominal ganglion. In the medulla of the optic lobes, numerous small interneurones hybridise with the probe, as do clusters of similar-sized neurones close to the roots of the ocellar nerves. These results indicate that the Leu callatostatin neuropeptides of the brain play a variety of roles in neurotransmission and neuromodulation. There are only three pairs of Leu callatostatin-immunoreactive neurones in the thoracico-abdominal ganglion, at least two pairs of which project axons along the median abdominal nerve to provide extensive innervation of the hindgut. The Leu-callatostatin peripheral neurosecretory cells are located in close association with both nerve and muscle fibres in the thorax. In addition to neuronal Leu-callatostatin, the presence of the peptide and its mRNA has been demonstrated in endocrine cells in the posterior part of the midgut. These observations provide an example of a named brain/gut peptide in an insect. PMID- 7781034 TI - Reversible histochemical modifications of endoplasmic reticulum following arginine vasopressin stimulation of granular cells of toad bladder. AB - The endoplasmic reticulum is generally absent from schematic representations of transport phenomena, although it shows a well-organized network in most transport epithelial cells. In order to examine the correlation between this organelle and cellular activity, bladders of Bufo marinus were studied under different experimental conditions and fixed by immersion in glutaraldehyde, followed by OsO4 impregnation for 3 days. Normal granular and mitochondria-rich cells showed a rich cytoplasmic network of canaliculi, well-impregnated by osmium deposits. Following a 2 to 15-min stimulation (serosal bath) with arginine vasopressin, the V2 receptor agonist dD-arginine-vasopressin or cyclic AMP (cAMP), the staining of endoplasmic reticulum in granular cells disappeared. After washing out of the hormone or the agonist, impregnation of the endoplasmic reticulum could be observed once again. Arginine vasopressin did not modify the impregnation of endoplasmic reticulum of either mitochondria-rich or basal cells. Our data indicate a correlation between the reactivity of endoplasmic reticulum to osmium, and a cAMP-dependent effect of arginine vasopressin through its V2 receptors. Incubation of arginine vasopressin through its V2 receptors. Incubation of toad bladders carried out with agents interfering with cellular calcium (calcium ionophores, high or low bath calcium) or with calcium release from the endoplasmic reticulum (TMB-8, thapsigargin) suggested that an early step in the cAMP-dependent effect of arginine vasopressin must involve the release of intracellular calcium from the endoplasmic reticulum. However, calcium ATPases in this organelle do not seem to participate in the hormonal effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781035 TI - Ovarian and uterine lymphatic drainage in Australian flying-foxes (genus Pteropus, suborder Megachiroptera). AB - Ovarian lymphatics of flying-foxes were traced to determine if they could transport hormones directly from ovary to ipsilateral uterine horn, thereby stimulating the localised endometrial growth which is characteristic of these animals. Intra-ovarian injections of ink and serial histological sections did not reveal any such connection. All major ovarian lymphatics and those from the cranial tip of each uterine horn drain cranially, terminating in 1 or 2 lymph nodes lying caudal to the ipsilateral kidney. For much of their course, the major ovarian lymphatics run in the adventitia of the ovarian venous sinus. This sinus encloses the coiled ovarian artery, which provides the major blood supply to the cranial end of the ipsilateral uterine horn. Some fine ovarian lymphatics run in the adventitia of the coiled ovarian artery. The enclosure of the coiled ovarian artery by the ovarian venous drainage is thought to provide the main route for transfer of steroids from ovarian vein to ovarian artery and thence to ipsilateral uterine horn. The ovarian lymphatics described here do not bypass the vascular pathway but provide an additional route for counter- or cross-current transfer of ovarian steroids to the ovarian arterial supply to the uterus. PMID- 7781036 TI - Reflective organelles in the anterior pigment epithelium of the iris of the European starling Sturnus vulgaris. AB - The ultrastructure and chemical composition of reflective organelles in the anterior pigment epithelium of the iris of the European starling Sturnus vulgaris were examined. The reflective organelles produced a diffuse white reflectance at the iris mid-section which was visible only when the stroma was removed. The pigment granules were clear, angular, and birefringent under the light microscope. In electron micrographs the granules were irregular in shape and density, sometimes crystalline in appearance, but more often they were lost during sectioning or staining. Guanine was abundant in the modified pigment epithelium of the starling, but not in the pigment epithelia of other birds that lacked birefringent granules. Pteridines, such as xanthopterin and leucopterin, were present in small amounts. Pteridines were also present in the iris stroma which had no reflective organelles. The reflective organelles in the starling pigment epithelium resemble both the reflecting platelets of lower vertebrate chromatophores and the reflective granules in the tapeta of various vertebrates. Possible derivation of the organelles from these sources is discussed. PMID- 7781037 TI - The genotype of bone marrow-derived inflammatory cells does not account for differences in skeletal muscle regeneration between SJL/J and BALB/c mice. AB - This study determined whether the genotype of bone marrow-derived inflammatory cells contributes to the more pronounced leukocytic exudation and extensive new muscle formation seen in SJL/J compared with BALB/c mice after a crush-injury (Mitchell et al. 1992). Female SJL/J mice were whole-body irradiated and reconstituted with male bone marrow from the BALB/c strain, and irradiated BALB/c females reconstituted with male SJL/J bone marrow. The mice were allowed to recover for 3 weeks and the tibialis anterior muscle (in a leg which had been protected from irradiation) was injured by crushing. At 3 and 10 days after injury the extent of necrotic debris, mononuclear leukocytic infiltration and new muscle formation was assessed in the muscles. The SJL/J mice reconstituted with BALB/c bone marrow showed extensive mononuclear leukocytic infiltration and clearance of necrotic debris when compared with BALB/c mice reconstituted with SJL/J bone marrow, and these strain-specific differences mirrored those seen with control bone marrow reconstituted hosts and non-irradiated hosts. The results show that the genotype of the bone marrow-derived macrophages is not responsible for the superior regeneration of crush-injured skeletal muscle in SJL/J mice, and it appears that factors intrinsic to the muscle tissue may be of central importance. PMID- 7781038 TI - Immunocytochemical localisation of some lysosomal hydrolases, their presence in luminal fluid and their directional secretion by human epididymal cells in culture. AB - The way in which the human epididymis modifies spermatozoa during their sojourn in this structure might be clarified by knowledge of the nature of its secretions. We have examined the presence of several lysosomal hydrolases in human epididymal tissue and fluids, and their synthesis and secretion by monolayer cultures. Tissues were obtained from men undergoing orchidectomy for prostatic carcinoma. The enzymes cathepsin D and acid alpha-glucosidase were localised in the lysosomes of epithelial cells from the corpus epididymidis, by an immunocytochemical technique. Cathepsin D was also found in epithelial cells of the efferent ducts within lysosomes, apical vesicles and multivesicular bodies. No immunolocalisation of acid glucosidase in the efferent ducts or on the microvilli of the corpus was demonstrable. Cathepsin D, beta-hexosaminidase (N acetylglucosaminidase) and alpha-glucosidase were measurable in the luminal fluid from the human corpus epididymidis; beta-hexosaminidase was secreted into the culture medium by confluent monolayers of epididymal and efferent duct cells. Immunoprecipitation of cell extracts and culture medium of these cultures incubated with 35S-methionine revealed that the precursors of cathepsin D and beta-hexosaminidase were synthesized and secreted by such monolayers. Thus, active lytic enzymes are secreted by the human epididymis and could modify sperm membranes. PMID- 7781039 TI - A histochemical study of the distribution of lectin binding sites in the developing oocytes of the lancelet Branchiostoma belcheri. AB - The distribution of carbohydrate moieties in lancelet (Branchiostoma belcheri) oocytes has been studied at different stages of development, using a peroxidase labeled lectin incubation technique, the PAS-reaction and Alcian Blue staining. Binding sites of 5 lectins, indicating the presence of different sugar moieties (Wheat germ agglutinin (WGA) for N-acetylglucosamine, Concanavalin A (Con A) for glucose/mannose, Helix pomatia agglutinin (HPA) for N-acetyl-D-galactosamine, Ricinus communis agglutinin (RCA-I) for galactose and Ulex europaeus agglutinin (UEA-I) for fucose), were identified and were shown to undergo considerable variation during oocyte development. In the previtellogenic stage, HPA, RCA-I and UEA-I were not identified on the oocyte surface, but WGA and Con A gave strongly positive reactions at this site. In the cytoplasm, 4 lectins (Con A, HPA, RCA-I and UEA-I) gave a weak or moderate reaction, and Con A was also observed in the perinuclear region. In vitellogenic oocytes, these 4 lectins were found to also bind to the nuclear envelope, karyoplasm and nucleolus, and, with the exception of Con A, could also be found in the nuclei of more mature stages. The cytoplasmic yolk granules and Golgi vesicles of the vitellogenic oocyte, were moderately positive for Con A, HPA, RCA-I and UEA-I, but HPA, RCA-I and UEA-I were only weakly bound at the oocyte surface. In mature oocytes, all 5 lectins bound moderately or strongly to yolk granules and cell surface. HPA, RCA-I and UEA-I bound moderately or strongly to various nuclear compartments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781040 TI - Tissue- and cell-specific distribution of creatine kinase B: a new and highly specific monoclonal antibody for use in immunohistochemistry. AB - A synthetic 17-mer peptide corresponding to an unique sequence in the amino terminal region of human creatine kinase B was used to raise a new and highly B subunit-specific monoclonal antibody, CK-BYK/21E10. We show here that the monoclonal antibody is suitable for immunohistochemistry of unfixed frozen sections as well as formaldehyde- or Bouin-fixed, paraffin-embedded sections of human, rabbit, and mouse tissues. Moreover, in the study of cell- and tissue specific distribution patterns, parallel Western blot analysis and immunoelectron microscopy is possible using this antibody. Our analyses demonstrate that creatine kinase B expression is restricted to a specific subset of cell types in various tissues. In brain, the B-subunit was found only in neurocytes, but not in glia cells. High expression was also observed in inner segments of photoreceptor cells and the outer plexiform layer of the retina, in the parietal cells of the stomach and in gut enterocytes, gallbladder and epithelial cells of the urogenital system. The possible roles of the creatine kinase/phosphocreatine-ATP system in these tissues are discussed. PMID- 7781041 TI - Adherence, proliferation and collagen turnover by human fibroblasts seeded into different types of collagen sponges. AB - We describe an in vitro model that we have used to evaluate dermal substitutes and to obtain data on cell proliferation, the rate of degradation of the dermal equivalent, contractibility and de novo synthesis of collagen. We tested three classes of collagenous materials: (1) reconstituted non-crosslinked collagen, (2) reconstituted collagen that was chemically crosslinked with either glutaraldehyde, aluminium alginate or acetate, and (3) native collagen fibres, with or without other extracellular matrix molecules (elastin hydrolysate, hyaluronic acid or fibronectin). The non-crosslinked reconstituted collagen was degraded rapidly by human fibroblasts. The chemically crosslinked materials proved to be cytotoxic. Native collagen fibres were stable. In the absence of ascorbic acid, the addition of elastin hydrolysate to this type of matrix reduced the rate of collagen degradation. Both elastin hydrolysate and fibronectin partially prevented fibroblast-mediated contraction. Hyaluronic acid was only slightly effective in reducing the collagen degradation rate and more fibroblast mediated contraction of the material was found than for the native collagen fibres with elastin hydrolysate and fibronectin. In the presence of ascorbate, collagen synthesis was enhanced in the native collagen matrix without additions and in the material containing elastin hydrolysate, but not in the material with hyaluronic acid. These results are indicative of the suitability of tissue substitutes for in vivo application. PMID- 7781044 TI - Dissociation of photoreceptors from whole heads of the fruit fly, Drosophila melanogaster. AB - Photoreceptor cells that were mostly free of extracellular material and suitable for most electrophysiological study procedures were dissociated from whole heads of the fruit fly, Drosophila melanogaster, by a simple "smash" technique employing gentle chopping by a razor blade through Parafilm sheets. A variety of commonly available proteolytic and glycolytic digestion enzymes were tested as additions to the basic dissociation procedure described. With the aid of Nomarski interference contrast optics, periodic acid-Schiff staining, and fluorescent labeling and microscopy methods, it was determined that proteolytic enzymatic digestion does little to enhance the dissociation procedure, and instead, often damages the cells that one is attempting to recover. Unexpectedly, certain glycolytic enzymes, when added to the basic procedure, appear to enhance the recovery of intact viable Drosophila photoreceptors that are stripped of most extracellular material. Based on these results, a hypothesis concerning the biochemical nature of the extracellular matrix of the Drosophila retina is proposed. Drosophila photoreceptors are an interesting model system for the study of invertebrate phototransduction and photoreceptor cell biology because of their many well-characterized mutant strains. The technique described here should produce clean viable photoreceptors or ommatidia that respond to light, and that are suitable for patch clamping or cell culture. PMID- 7781043 TI - Expression of neural cell adhesion molecules, NCAMs, and their polysialylated forms, PSA-NCAMs, in the developing rat pituitary gland. AB - Neural cell adhesion molecules (NCAMs) can undergo post-translational modifications, such as the addition of polysialic acid chains, thus generating PSA-NCAMs, which are expressed mainly during development. Since polysialylation considerably modifies NCAM adhesivity, expression of NCAMs and PSA-NCAMs has been investigated in the developing hypophysis by immunohistochemistry. At embryonic day 13 (E13), an antibody against NCAM outlined all cellular profiles in the entire Rathke's pouch; this labelling persisted until adulthood. NCAM expression increased in all lobes during development and concerned all pituitary cell types. In contrast, at E13, PSA-NCAMs were only detected in the neural lobe, solely constituted of pituicytes at this stage, and the tuberal lobe, the only lobe expressing hormonal mRNA at the same stage. PSA-NCAMs expression increased in the neural lobe at E17 with the arrival of the neurosecretory fibres and persisted into adulthood. In the anterior lobe, PSA-NCAMs appeared at E15 where their distribution was similar to that of the differentiating corticotrophic cells; at subsequent stages, their expression extended to the whole anterior lobe. Only two cell types, corticotrophic and somatotrophic cells, remained labelled in the adult gland. In the intermediate lobe, melanotrophic cells never expressed PSA NCAMs but these were expressed on folliculo-stellate cells at birth, preceding the onset of innervation. These results suggest that NCAMs and PSA-NCAMs play a role in pituitary histogenesis, cell differentiation and neurointermediate lobe innervation. PMID- 7781045 TI - [A study on the relationship between malignant tumour mortality and environmental pollution in Beicun countryside of Datong City]. AB - The paper reports investigations on malignant tumor mortality in Beicun countryside of Datong city, with Hua yuan tun countryside as the control group. The result showed that malignant tumor mortality (117.04/10(5)) in Beicun countryside was significantly higher than that in the control group (61.06/10(5)). The nitrate and nitrite in drinking water and five kinds of vegetables in Beicun countryside were significantly higher than those in the control group (P < 0.05 - P < 0.001). Serum Cu and Cu/Zu levels in the inhabitants of Beicun countryside were significantly higher than those in the control group (P < 0.001 and P < 0.01). The benzo (a) pyrene and airborne particulates in Beicun countryside area were higher than those in the control group area. The results showed that the malignant tumor mortality was strongly correlated with severe pollution of vegetables, drinking water and air. PMID- 7781042 TI - Intermediate filament typing of the human embryonic and fetal notochord. AB - In order to characterize human notochordal tissue we investigated notochords from 32 human embryos and fetuses ranging between the 5th and 13th gestational week, using immunohistochemistry to detect intermediate filament proteins cytokeratin, vimentin and desmin, the cytokeratin subtypes 7, 8, 18, 19 and 20, epithelial membrane antigen (EMA), and adhesion molecules pan-cadherin and E-cadherin. Strong immunoreactions could be demonstrated for pan-cytokeratin, but not for desmin or EMA. Staining for pan-cadherin and weak staining for E-cadherin was found on cell membranes of notochordal cells. Also it was demonstrated that notochordal cells of all developmental stages contain the cytokeratins 8, 18 and 19, but not 7 or 20. Some cells in the embryonic notochord also contained some vimentin. Vimentin reactivity increased between the 8th and 13th gestational week parallel to morphological changes leading from an epithelial phenotype to the chorda reticulum which represents a mesenchymal tissue within the intervertebral disc anlagen. This coexpression reflects the epithelial-mesenchymal transformation of the notochord, which also loses E-cadherin expression during later stages. Our findings cannot elucidate a histogenetic germ layer origin of the human notochord but demonstrate its epithelial character. Thus, morphogenetic inductive processes between the human notochord and its surrounding vertebral column anlagen can be classified as epithelial-mesenchymal interactions. PMID- 7781046 TI - [Evaluation of segregation ratio and hereditability of esophageal cancer--a comparative epidemiologic study in Huai'an County]. AB - A genetic epidemiologic case-control study including 407 pedigrees (249 cases and 158 controls) was carried out to estimate the segregation ratio and the hereditability (h2) of esophageal cancer by using the method of Li-Mantel-Gart and Falconer, respectively, and to compare the genetic epidemiologic features from the other cancers. The results showed that the segregation ratio of esophageal cancer was 0.1347, significantly less than 0.25 and the genetic model belonged to polygenetics. The h2 of esophageal cancer was 21.41%, 20.23% for female and 13.57% for male. It is concluded that genetic factor is one of the risk factors for esophageal cancer and specially of importance for female, but it is not a main risk factor for esophageal cancer. The results of comparative epidemiologic study among the cancers of lung, stomach, liver and large bowel showed that the segregation ratios of the cancers (except stomach, no data) were all less than 0.25, and the h2 of gastric and liver cancers were higher, which were 52.40% and 51.85%, respectively. PMID- 7781047 TI - [Investigation on scoliosis incidence among 24,130 school children]. AB - Through the screening on scoliosis among 24,130 school children in Hu Guan County, Shanxi Province, it showed that the forward-bending test was positive in 1,794 children (7.4 per cent), with male 3.64 per cent and female 3.8 per cent. The hump inclination angles that were more than 4 degrees were found in 665 children (2.75 per cent). The Cobb angles that were more than 10 degrees were found in 347 children. The incidence rate was 1.44 per cent, with a male to female ratio of 1:1.17. Most of them were idiopathic scoliosis. PMID- 7781048 TI - [Detection of human cytomegalovirus in urine by polymerase chain reaction]. AB - Polymerase chain reaction (PCR) amplification was set up with double primer pairs of major immediate-early and late gene in order to detect human cytomegalovirus (HCMV) from urine. This method was applied to the detection of HCMV in clinical samples of urine from renal transplant recipients. The result indicated that the primers did not cross react with other members of the herpes family of virus and human genomic DNA; that the HCMV AD169 tissue culture mixture used and the dilutions to estimate the sensitivity of PCR relative to tissue culture, 2.5 microliters of a 10(-3) dilution of the culture (625fg HCMV DNA) assayed were detected by direct gel analysis; that 25 of 30 samples of urine from the renal transplant recipients (serum HCMV IgM positive) were positive. It is conclude that PCR amplification is a valuable tool for diagnoses of HCMV infection in renal transplant recipients. PMID- 7781049 TI - [Application of biological markers in epidemiologic studies]. PMID- 7781050 TI - [A cohort study and KAP investigation of HIV infected persons in Ruili, and other counties in Yunnan, 1994]. AB - In 1994, an cohort study of drug users had continued in Longchuan and Luxi counties, Ruili city. The cohort study for drug users had been established since 1992 and total 522 drug users were investigated. Sixty five sera samples were collected, including 26 HIV negatives intravenous drug users in 1992 and 39 of them in 1993. The result shown that 10 sera samples are positives. Of sixty five samples tested, the rate of HIV infectious for IVDU in Ruili, Longchuan and Luxi were 25.0%, 16.3% and 0.0% respectively. Total of 46 HIV positives samples were found from 105 blood samples among the IVDU who were newly included in the cohort study in 1994. Of these samples, the rates of HIV infection in Ruili, Longchuan and Luxi were 61.8%, 38.5% and 0.0% respectively. The result of KAP investigation from 522 drug users has shown that there is a marked difference of the rate of HIV infections in the nationalities, occupations, education (P < 0.01). The main reason contributing the low rate of HIV infections in Luxi county is that the IVDU mainly are the Han nationality with higher education level, as well as travelling less to Burma. PMID- 7781051 TI - [Investigation of mortality among HIV-infected intravenous drug users in Ruili region of Yunnan province]. AB - The investigation of death condition of HIV infected intravenous drug users (IVDU) was conducted with a retrospective cohort study in Ruili city of Yunnan province from 1989-Oct to 1993-Oct, the deaths among 395 HIV+ IVDUs add up to 61 and the mortality is 15.4%, which has significant difference compared to the death level of control cohort composed by 192 HIV- IVDUs (add up to 18). The relative risk of death is 1.6 (95% confidence interval 1.0-2.5). After classified by the cause of death, it was found that both maintain high accidence mortality caused mainly by narcotism, violence and suicide. But in death group caused by diseases, the mortality of HIV+ IVDU (8.4%) is much higher than HIV- IVDU (3.1%) (95% confidence interval 1.2-6.1). We also compared non-AIDS mortality between HIV+ and HIV- IVDU according to data of HIV/AIDS surveillance which showed 2 patients died of AIDS in HIV+ IVDU. The difference is also significant (13.8% in HIV+, but 7.9% in HIV- IVDU) and the relative risk is 1.7 (95% confidence interval 1.0-2.8). The results indicated that the lever of reported AIDS cases were probably lower than that of actual AIDS cases existing. PMID- 7781052 TI - [Cost-benefit analysis on immunization of newborns with hepatitis B vaccine in Jinan City]. AB - The decision tree model cost-benefit analysis method was used to analyse the strategies and economic benefits of immunization of newborns with hepatitis B vaccines in Jinan City. The results showed that all the three vaccination strategies could all produce positive benefits. Their BCR were 42.41 to 48.01. Through the decision analysis, it concluded that stress should be laid on the blocking of mother-to-infant transmission, and that if there are sufficient HB vaccines, all newborns should be vaccinated. In addition, the results of sensitivity analysis indicate that the benefits of HB vaccination are outstanding and quite stable. PMID- 7781053 TI - [A seroepidemiologic survey on HCMV infection in pregnant women]. AB - A survey on antibodies to HCMV-IgM was carried out with the solid-phase ELISA in 6,428 pregnant women who were given perinatal medical care in six regions of Henan Province. The positive rate was 1.1%. It was found that women of different ages, stages and numbers of pregnancy had the same positive rate. And the rate in autumn was slightly higher than those in other seasons. PMID- 7781054 TI - [A study on the risk factors of Legionella infection in children]. AB - In order to understand the risk factors of legionella infection in children a case-control study with two kinds of controls was conducted. The stepwise regression analysis included age, sex, season and immunosuppressive therapy in regression equation. The non-conditional logistic regression analysis showed that age, passive smoking and touching soil were associated with legionella infection. The statistics analysis also showed that there were dose-response relationship between age, passive smoking and immunosuppressive therapy and the frequency of legionella infection in children. It was suggested that age, season, immunosuppressive therapy, passive smoking and touching soil were risk factors for legionella infection. PMID- 7781055 TI - [Study on carboxylated latex agglutination test for serodiagnosis of human and animal brucellosis]. AB - A carboxylated latex agglutination test was developed for detecting antibodies in sera from 372 human and animal brucellosis. Of which 94 sera from human was detected by ELISA. The latex was chemical-linked with B. melitensis 16M and extracted with 5% NaCl. Comparing with RBPT in detecting antibodies with brucellosis, the LAT was more stable and specific; the positive or negative results detected by LAT were consistent with those by SAT and ELISA. LAT may detect both IgG and IgM antibodies to Brucella in Human and animal. It is concluded that LAT is stable, specific, sensitive and practicable for the serodiagnosis of brucellosis. PMID- 7781056 TI - [A report of epidemiology investigation on 222 infants with tetanus in Pingdingshan City from 1990 to 1991]. AB - A total of 222 in-patients with tetanus had been investigated in Ping Ding Shan City (including 4 counties) from 1990 to 1991. The incidence in 1990 was 62.8/10(5), the special incidence was 2.44/1000. But in 1991, they were 48.1/10(5) and 1.97/1000, respectively. The male-to-female ratio was 3:1. 89.64% infants came from the countryside, and 99.6% infants were delivered in an old way. PMID- 7781057 TI - [The prevalence of Toxoplasma infection among pregnant women and their newborn infants in Chengdu]. AB - Purpose of the study was to determine the prevalence of toxoplasma infection among the pregnant women and their newborn infants in Chengdu and to identify risk factors of acquiring toxoplasma infection. The Maternal and Child Health Hospital was selected by random cluster sampling method in the study. Each pregnant women admitted to the above hospital consecutively and her surviving newborn at birth were included in this survey. History, physical examination and blood specimens were obtained from 1,211 pairs of mother-newborns. ELISA was used to detect toxoplasma IgG and IgM antibodies. Results revealed that sera prevalence of toxoplasma IgG antibodies and IgM antibodies of pregnant women were 39.14% and 4.21% respectively. Seraprevalence of toxoplasma IgM antibodies of newborn infants was 1.07%. Congenital malformation of newborn infants may be associated with congenital toxoplasma infection (P < 0.05, OR = 6.32). PMID- 7781059 TI - No end yet to messenger RNA 3' processing! PMID- 7781058 TI - Qualifying for the license to replicate. PMID- 7781060 TI - Sense from nonsense: RNA editing in mitochondria of kinetoplastid protozoa and slime molds. PMID- 7781061 TI - Arrestin binding determines the rate of inactivation of the G protein-coupled receptor rhodopsin in vivo. AB - G protein-coupled receptor inactivation is a crucial feature of cellular signaling systems; this process determines the catalytic lifetime of the activated receptor and is necessary for response termination. Although previous work has indicated a class of models in which several sequential steps are required for receptor inactivation, the rate-limiting event is still unclear. In this paper, we develop a theory that describes the kinetics of inactivation of the G protein-coupled receptor rhodopsin based on the rate of arrestin binding and test the theory using a combination of genetic and electrophysiological techniques in Drosophila photoreceptors. The theory quantitatively describes the inactivation kinetics of activated rhodopsin in vivo and can be independently tested with molecular and spectroscopic data. The results demonstrate that the rate of arrestin binding determines the kinetics of receptor inactivation in vivo and thus is the event that controls signal amplification at the first step of this G protein-coupled transduction cascade. PMID- 7781062 TI - Rac mediates growth factor-induced arachidonic acid release. AB - Growth factor-induced stress fiber formation involves signal transduction through Rac and Rho proteins and production of leukotrienes from arachidonic acid metabolism. In exploring the relationship between these pathways, we found that Rac is essential for EGF-induced arachidonic acid production and subsequent generation of leukotrienes and that Rac V12, a constitutively activated mutant of Rac, generates leukotrienes in a growth factor-independent manner. Leukotrienes generated by EGF or Rac V12 are necessary and sufficient for stress fiber formation. Furthermore, leukotriene-dependent stress fiber formation requires Rho proteins. We have therefore identified elements of a pathway from growth factor receptors that includes Rac, arachidonic acid production, arachidonic acid metabolism to leukotrienes, and leukotriene-dependent Rho activation. This appears to be the major pathway by which Rac influences Rho-dependent cytoskeleton rearrangements. PMID- 7781063 TI - Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway. AB - Drosophila yan has been postulated to act as an antagonist of the proneural signal mediated by the sevenless/Ras1/MAPK pathway. We have mutagenized the eight MAPK phosphorylation consensus sites of yan and examined the effects of overexpressing the mutant protein in transgenic flies and transfected S2 cultured cells. Our results suggest that phosphorylation by MAPK affects the stability and subcellular localization of yan, resulting in rapid down-regulation of yan activity. Furthermore, MAPK-mediated down-regulation of yan function appears to be critical for the proper differentiation of both neuronal and nonneuronal tissues throughout development, suggesting that yan is an essential component of a general timing mechanism controlling the competence of a cell to respond to inductive signals. PMID- 7781064 TI - Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. AB - Male-specific lethal-2 (msl-2) is a RING finger protein that is required for X chromosome dosage compensation in Drosophila males. Consistent with the formation of a dosage compensation protein complex, msl-2 colocalizes with the other MSL proteins on the male X chromosome and coimmunoprecipitates with msl-1 from male larval extracts. Ectopic expression of msl-2 in females results in the appearance of the other MSL dosage compensation regulators on the female X chromosomes and decreased female viability. We suggest that msl-2 RNA is the primary target of SxI regulation in the dosage compensation pathway and present a speculative model for the regulation of two distinct modes of dosage compensation by SxI. PMID- 7781065 TI - Visualization of chromosomal domains with boundary element-associated factor BEAF 32. AB - We have purified two proteins from Drosophila that bind to the scs' boundary element of the hsp70 domain at locus 87A7. Their palindromic binding sites (CGATA TATCG) symmetrically abut the previously mapped hypersensitive site of scs'. We have cloned a cDNA for one of these proteins, BEAF-32 (boundary element associated factor of 32 kDa). It encodes a novel protein that is bound to scs' but not scs in vivo. Immunostaining localizes BEAF to hundreds of interbands and many puff boundaries on polytene chromosomes, suggesting that a chromosomal domain consists of a band (or puff) and part of the flanking interbands. Enhancer blocking assays implicate the palindromic binding site in boundary function. The lack of enhancer blocking in transiently transfected cells suggests an involvement of chromatin, nuclear structure, or both in boundary function. PMID- 7781066 TI - CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP. AB - To investigate the function of the autophosphorylated form of CaMKII in synaptic plasticity, we generated transgenic mice that express a kinase that is Ca2+ independent as a result of a point mutation of Thr-286 to aspartate, which mimics autophosphorylation. Mice expressing the mutant form of the kinase show an increased level of Ca(2+)-independent CaMKII activity similar to that seen following LTP. The mice nevertheless exhibit normal LTP in response to stimulation at 100 Hz. However, at lower frequencies, in the range of 1-10 Hz, there is a systematic shift in the size and direction of the resulting synaptic change in the transgenic animals that favors LTD. The regulation of this frequency-response function by Ca(2+)-independent CaMKII activity seems to account for two previously unexplained synaptic phenomena, the relative loss of LTD in adult animals compared with juveniles and the enhanced capability for depression of facilitated synapses. PMID- 7781068 TI - Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. AB - Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with main-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one third of the domain, explaining how the activator promotes insertion of PKC into membranes. PMID- 7781067 TI - Impairment of spatial but not contextual memory in CaMKII mutant mice with a selective loss of hippocampal LTP in the range of the theta frequency. AB - We assessed hippocampal-dependent memory in mice with a Ca(2+)-independent form of CaMKII generated by the introduction of an aspartate at amino acid 286. The CaMKII-Asp-286 mice show normal LTP at high frequency stimulation, but in the 5 10 Hz range, they show a shift in the frequency-response curve favoring LTD. This range of frequencies is similar to the theta rhythm, which is associated with exploration in rodents. Using the Barnes maze to assess spatial memory, we found the transgenic mice could not learn to navigate to a specific location using spatial cues. In contrast, one line of transgenic mice performed normally in contextual fear conditioning, a task that is also hippocampal dependent. This dissociation between spatial and contextual memory suggests that even though both require the hippocampus, they may be mediated by different synaptic mechanisms. PMID- 7781069 TI - Initiation of V(D)J recombination in a cell-free system. AB - Cells performing V(D)J recombination make specific cuts in DNA at recombination signal sequences. Here, we show that nuclear extracts of pre-B cell lines carry out this specific cleavage. The products of cleavage are the same as found previously in thymocytes: full-length, blunt, 5'-phosphorylated signal ends, and covalently sealed (hairpin) coding ends. A complete signal sequence is required. Recombinant RAG1 protein greatly increases activity and complements an inactive extract from a RAG1 (-/-) pre-B cell line. When the extracts are fractionated, cleavage activity correlates with the presence of RAG2 protein. These results suggest that RAG1 and RAG2 are components of the V(D)J recombinase. PMID- 7781070 TI - A role for recombination junctions in the segregation of mitochondrial DNA in yeast. AB - In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygotes relative to wild-type mtDNA. This segregation advantage is abolished by mutations in a gene, MGT1, that encodes a recombination junction-resolving enzyme. We show here that resolvase deficiency causes a larger proportion of molecules to be linked together by recombination junctions, resulting in the aggregation of mtDNA into a small number of cytological structures. This change in mtDNA structure can account for the increased mitotic loss of mtDNA and the altered pattern of mtDNA segregation from zygotes. We propose that the level of unresolved recombination junctions influences the number of heritable units of mtDNA. PMID- 7781071 TI - The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. AB - Mutations in the APC gene are responsible for various familial and sporadic colorectal cancers. Min mice carry a dominant mutation in the homolog of the Apc gene and develop multiple adenomas throughout their small and large intestine. Quantitative trait loci studies have identified a locus, Mom1, which maps to the distal region of chromosome 4, that dramatically modifies Min-induced tumor number. We report here the identification of a candidate gene for Mom1. The gene for secretory type II phospholipase A2 (Pla2s) maps to the same region that contains Mom1 and displays 100% concordance between allele type and tumor susceptibility. Expression and sequence analysis revealed that Mom1 susceptible strains are most likely null for Pla2s activity. Our results indicate that Pla2s acts as a novel gene that modifies polyp number by altering the cellular microenvironment within the intestinal crypt. PMID- 7781073 TI - [Principles of ontogenetic research on the central nervous system]. PMID- 7781072 TI - [Membrane transport of macromolecules and particles: exocytosis and endocytosis]. PMID- 7781074 TI - [The role of GTP-binding proteins in hormone signal transfer]. PMID- 7781075 TI - [Pathophysiology of calcium metabolism regulation]. PMID- 7781076 TI - [Mechanisms of learning, memory and their development]. PMID- 7781078 TI - [Ion channels]. PMID- 7781079 TI - [Role of the central cholinergic system in behavior during stress]. PMID- 7781077 TI - [Functional hemispheric asymmetry in man]. PMID- 7781081 TI - [Hormonal thermogenesis]. PMID- 7781080 TI - [Present findings on the interrelation between the immune and the endocrine systems]. PMID- 7781082 TI - [The importance of nutrition for the developing organism]. PMID- 7781084 TI - [Basics of hemodynamic values and their regulation]. PMID- 7781083 TI - [Mechanisms of oxygen transport]. PMID- 7781085 TI - [Humoral regulation and endocrine function of the cardiovascular system]. PMID- 7781086 TI - The prevalence of hepatitis B surface antigen in the Gampaha district. AB - OBJECTIVE: To assess the prevalence and some epidemiological features of hepatitis B surface antigen (HBsAg) status in the Gampaha district. DESIGN: Community based survey. SETTING: The district of Gampaha. SUBJECTS: All individuals over six months of age who were resident in the Gampaha district for a period over one month at time of survey. RESULTS: The HBsAg positivity rate in the Gampaha district was estimated to be 2.5% (95% C.I. 2% to 3%). This places the area in the intermediate endemicity zone as classified by WHO. The epidemiology indicates horizontal intrafamilial spread being more important in the population studied, than vertical, parenteral or sexual routes of transmission. CONCLUSIONS: The study suggests that immunisation in early childhood is an important measure in prevention of the infection in this district. PMID- 7781087 TI - Raised serum IgE levels in chronic inflammatory lung diseases. AB - OBJECTIVE: To study the serum IgE response in nonallergic subjects with chronic inflammatory lung diseases. SETTING: Christian Medical College Hospital, Vellore. SUBJECTS: Twenty six patients with bronchiectasis, five with pulmonary mycosis referred from all over India and 30 healthy subjects. MAIN OUTCOME MEASURES: Serum IgE value (determined by radioimmuno assay) above the upper limit of normal control range (136 to 948 iu/ml) was considered as raised level. RESULTS: Of the 26 patients with bronchiectasis 13 had pyogenic infections, six had pulmonary tuberculosis; in six patients sputum culture was sterile while another patient had herpes zoster. Five cases of mycosis included one each of actinomycosis, aspergillosis, blastomycosis, cryptococcosis and nocardiasis. The serum IgE levels were raised in 20 (65%) of the 31 patients. CONCLUSION: Associated bacterial, fungal and parasitic infections were probably responsible for inducing an hyper-IgE response in these non-allergic subjects. PMID- 7781088 TI - Unvisited vistas of the nervous system. PMID- 7781089 TI - The case for a national integrated diabetes service. PMID- 7781090 TI - Some doctors celebrated for their non-medical achievements. PMID- 7781091 TI - Endemic multinodular goitre--management strategies. PMID- 7781092 TI - Decompression sickness: recovery after delayed recompression. AB - Two patients with Type II decompression sickness with good recovery following delayed recompression therapy are described. These are the first two cases of successful recompression therapy for this diving hazard to be reported in Sri Lanka. The risks taken by Sri Lankan divers and prevention of diving related medical disorders are discussed. PMID- 7781093 TI - Idiopathic thrombocytopaenic purpura presenting as post-partum haemorrhage. AB - We describe a patient with idiopathic (immune) thrombocytopaenic purpura who presented with postpartum haemorrhage. The patient did not have any external manifestations of idiopathic thrombocytopaenic purpura on admission but the diagnosis was suspected after examination of the baby. PMID- 7781094 TI - Congenital nephrotic syndrome. AB - A six week old baby girl from a closed Malay community in Hambantota presented with gradually increasing oedema since two weeks of age. She was oedematous, with gross non selective proteinuria, hypoproteinaemia and hypercholesterolaemaia. Congenital nephrotic syndrome is extremely rare and has not been reported previously in Sri Lanka. PMID- 7781095 TI - Chediak-Higashi syndrome. PMID- 7781096 TI - The intermediate rainfall zone as a source of malaria epidemics in Sri Lanka. PMID- 7781097 TI - Atypical presentations of malaria associated with chloroquine resistance. PMID- 7781098 TI - Unidentified snake bite with "pure" nephrotoxicity. PMID- 7781099 TI - Kikuchi's disease--a recognised cause for benign lymphadenopathy. PMID- 7781101 TI - Tumour of the pancreas with unusual clinicopathological features. PMID- 7781100 TI - Abuse of paracetamol in childhood fever. PMID- 7781102 TI - Pure choriocarcinoma of ovary, probably non-gestational in origin. PMID- 7781103 TI - Prevention of AIDS in Sri Lanka: are we doing the best for our people? PMID- 7781104 TI - A Sri Lankan family with lipoid proteinosis. PMID- 7781105 TI - Two children with acute leukaemia presenting with renal masses. PMID- 7781106 TI - [Current status and perspective of researches in cardiovascular pathology]. PMID- 7781107 TI - [Immunohistochemical observations on production and distribution of endothelin in atherosclerosis plaques]. AB - An analysis of endothelin in atherosclerotic plaques using immunohistochemical methods showed that endothelin not only existed in endothelial cells, large amounts were also found in the proliferating intimal vascular smooth muscle cells (VSMC). In the de-endothelized thoracic aorta of rats, significant amounts of endothelin could be produced by proliferating intimal VSMC. Radio-immunological studies demonstrated that the extent of VSMC proliferation was in direct ratio to endothelin content, which suggests that production of endothelin is related to proliferation of VSMC in atherosclerotic plaques. PMID- 7781108 TI - [Expression and significance of HBV DNA and its 5 antigens in liver cirrhosis]. AB - Hepatitis B virus (HBV) DNA and its 5 antigens were studied in 225 cases of paraffin-embedded sections of human liver cirrhosis obtained by biopsy. HBxAg, pre-S1 and pre-S2 antigens were detected by immunohistochemical ABC method, HBsAg and HBcAg by PAP method. HBV DNA by in situ hybridization, and both HBV DNA and HBsAg, HBxAg or HBcAg by double labelling technique of immunohistochemistry and in situ hybridization respectively. The results showed that the positive rates were 70.0% (128/183) for HBsAg, 64.4% (85/132) for pre-S1 antigen, 61.4% (81/132) for pre-S2 antigen, 75.3% (113/150) for HBxAg, 22.4% (39/174) for HBcAg and 62.4% (58/93) for HBV DNA respectively. The double labelling positive rates were 37.3% (19/51) for both HBV DNA and HBsAg, 86.3% (44/51) for both HBV DNA and HBxAg and 39.2% (20/51) for both HBV DNA and HBcAg respectively. More than 80% of the cases with positive sections for HBV DNA and its 5 antigens were associated with liver cell dysplasia (LCD). The results of this study suggest that the occurrence and development of liver cirrhosis were closely related to chronic infection of HBV in China. PMID- 7781109 TI - [Detection of HBV DNA and HBsAg in HCC and pericarcinomatous tissues using double labelling technique]. AB - 40 cases of hepatocellular carcinoma (HCC) and their surrounding tissues were studied on paraffin-embedded sections by in situ hybridization and immunohistochemical double labelling techniques. The positive rates of HBV DNA and HBsAg were 65% and 82.5% respectively, suggesting that HBV infection is a significant cause of HCC. HBV DNA and HBsAg signals in the pericarcinomatous tissues were stronger than that in cancer cells. Reduced replication caused by integration of HBV DNA in HCC may explain this phenomenon. We found that the small "piece-meal like" inclusions which existed only in HCC may be a special cancer related pattern of HBsAg. There were stronger signals of HBsAg in the small cell LCD than in other pericarcinomatous lesions, supporting the theory that the small cell LCD is more likely to be a precarcinomatous lesion. PMID- 7781110 TI - [Iron overload and iron deficiency regulate ED1 and ED2 expression in spleen macrophages of rats]. AB - Monoclonal antibodies ED1 and ED2 can recognize epitopes on the spleen macrophage related with its antigen presenting activity. Immunohistochemical and histochemical methods were used to show the influence of iron overload and iron deficiency on the expression of ED1, ED2 and phagocytic functions of the macrophages in the spleen. We found that iron overloaded rats had large amounts of hemosiderin deposits in the macrophages of red and white pulp with reduced expression of ED1, ED2 and phagocytic function. It is suggested that iron concentration can regulate the expression of ED1, ED2 and phagocytic activity of the macrophage, which may in turn influence its antigen presentation and anti infection functions. PMID- 7781111 TI - [Gene expression of growth factors, growth factor receptor and oncogenes in human lung cancer cell lines]. AB - Gene expression of growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), oncogenes such as c-myc, N-ras, c-erbB2 and tumor suppressor gene P53 were studied in 4 human lung cancer cell lines using Northern blot technique. Among these cell lines were 2 adenocarcinoma cell lines, one large cell carcinoma cell line and one small cell carcinoma cell line. Expression of EGF and TGF alpha mRNAs were found in all 4 cell lines and EFGR mRNA was seen in 3 out of 4 cell lines. Among these cell lines, 2 cell lines with weaker expression of EGF and TGF alpha, expressed c-myc mRNA. Another 2 cell lines had no c-myc but expressed large amounts of EGF and TGF alpha mRNA. No expression of N-ras, c-erbB2 and p53 were found in these cell lines. The results indicate the presence of autocrine loop of growth factors in these cancer cells. The autostimulation of growth factors may be the main cause for the uncontrolled growth of cancer cells. After treating the cancer cells with EGF, anti-EGF and anti-EGFR antibodies, EGF was found to exert a mild stimulating effect on the growth of one cell line, but no effect on the other cell lines. Anti-EGF and anti-EGFR antibodies inhibited the cell growth on all cell lines. These results provided further evidence for the presence of autocrine loop of growth factors in these lung cancer cell lines. PMID- 7781112 TI - [The detection of p53 gene and HPV16 oncogene in cervical carcinoma]. AB - Special primers of HPV16 E6 and E7 ORFs as well as p53 exon 7 were used with PCR, PCR-SSCP technique to study 35 cervical carcinoma specimens. The results were as follows: (1) HPV16 E6 and E7 DNA were found in 25/35 specimens (71.42%). However, only 11/35 (31.42%) had E6, E7 ORFs Simultaneously; 3/35 (8.57%) had E6 ORFs and 11/35 (31.42%) had E7 ORFs, indicating that the distribution of E6 E7 genes were heterogeneous in cervical carcinoma. (2) No mutation and loss of heterogeneity of p53 exon 7 was found in any of the 35 specimens, indicating that the alteration of p53 exon 7 in cervical carcinoma was uncommon. PMID- 7781113 TI - [Pathological research on isolated microcallus formation in 576 vertebrae]. AB - 576 vertebrae specimens obtained from 24 autopsy cases were studied for microcallus. Microcallus consisted of osteocytes which originated from osteoblasts located on the surface of trabeculae and from medullary reticulum cells. In the early stage, microcallus is immature woven bone which later transforms into mature lamellar bone. The incidence of microcallus is related to stress on the vertebral body and to the age of the patient, therefore, most microcallus were found in the lumbar vertebrae and in the elderly. PMID- 7781114 TI - [A study on human dental embryology in an endemic high fluorosis region]. AB - In a high endemic fluorosis area in Guizhou, China, 40 human fetuses delivered by induced abortion during the 5th-8th month of gestation were utilized to study dental embryonic samples under transmission electron microscope (TEM). Compared with normal controls, ultrastructure findings in the ameloblast cell organs include swelling of mitochondria, enlargement of SER, increase in RNA granules and RER. This study suggests that the irregularities of the collagenous fibers and crystallites are due to the maldevelopment of the ameloblast Tome's processes, which explains the mechanism of motteled enamel. PMID- 7781115 TI - [Olfactory neuroblastoma: a histopathological ultrastructural and immunohistochemical study of 11 cases]. AB - Eleven cases of olfactory neuroblastoma (ONB) were studied histopathologically, ultrastructurally and immunohistochemically. Light microscopical examination showed the tumor cell nests separated by fibrous connective tissue (present in 10/11 ONB), Homer-Wright rosette and/or Flexner rosette (9/11 ONB) and acidophilic fibrillary background (8/11 ONB). Ultrastructurally, there were neurosecretory granules (2/2 ONB) and neurofibrils (1/2 ONB) in cytoplasm of tumor cells. A panel of antibodies were used to characterize the immunohistochemical staining profile of ONB. The following results were obtained for the 11 neoplasms that were immunostained: NSE 11/11 (+), S-100 3/11 (+), Vimentin 4/11 (+), Keratin 1/11 (+) and NF, EMA, CEA, LCA all negative respectively. The significance of the morphological and immunohistochemical features of ONB in diagnosis and differential diagnosis were discussed. PMID- 7781116 TI - [Detection and quantification of lipoprotein (a) in atherosclerotic lesions of human aorta]. AB - Lipoprotein(a) [Lp(a)] represents an independent risk factor for atherosclerotic disease. In the present study, the extent to which Lp(a) accumulated in normal and various degrees of atheromatous lesions and the distribution pattern of Lp(a) in these lesions have been studied in thoracic aorta from the autopsy tissues by means of immunohistochemistry, immunoelectronic microscopy, enzyme-linked immunosorbent assay and computer-assisted image processing. Lp(a) was found to be localized preferentially in lesion areas and had its own distribution pattern in each kind of lesion. Lp(a) associated primarily with extracellular matrix and was detected in only a small number of foamy cells. Apolipoprotein B was also detected, whose staining pattern was always found to be congruent with that of Lp(a). This suggests that the immunoreactivity of apoB is related to the presence of Lp(a) at least in part, since Lp(a) possesses apoB in addition to apo(a). It was concluded that both low density lipoprotein and lipoprotein(a) play an important role in the pathogenesis of atherosclerosis. PMID- 7781117 TI - [Studies on the histological classification of proliferative disease of breast and its relation with breast carcinoma]. AB - According to the degree of fibroplastic proliferation, proliferative disease of breast can be divided into three types: lobular hyperplasia type, fibroadenosis type and fibrosclerosis type. Each type could have simple or compound lesions. The latter include: atypical hyperplasia of duct epithelial cells, large sweat gland metaplasia, cyst and fibroadenoma formation. The progress of lesions coincided with the increase of age. The age of fibrosclerosis patients were close to that of patients with breast carcinoma accompanied with proliferative breast disease. The level of PCNA expression in the three types of proliferative breast disease increased progressively and the level of PCNA expression in fibrosclerosis and breast carcinoma being similar. It is emphasized that in the fibrosclerosis type hyperplasia, the presence of twisting, fragmentation or incomplete encirclement of the periductal myoepithelial cells as well as the basement membrane of the tubules may be considered as a warning to call one's attention to follow up patients closely. PMID- 7781118 TI - [Detection of human papillomavirus in condyloma acuminata tissues]. AB - We used immunohistochemical technique, in situ hybridization and polymerase chain reaction to detect HPV capsid antigen (HPV-Ag) and HPV-DNA sequences in genital condyloma and pseudocondyloma of vulvae tissues. We also observed the relation between HPV distribution in condylomas and their histological changes. RESULTS: 71.4% of condylomas were positive for HPV-Ag with IMHC, 96.5% of condylomas were positive for HPV6/11 DNA with ISH, and 100% of condylomas were positive for HPV6/11/16/18DNA with PCR. Only 21.4% of pseudocondylomas of vulvae were positive for HPV6/11/16/18DNA with PCR. By observing the distribution of labelled HPV-Ag and HPV-DNA, we found a close relation between HPV proliferative infection and the specific changes of condylomas. PMID- 7781119 TI - [Effects of retinoids on the invasiveness and metastasis of neoplastic cells and related mechanism]. PMID- 7781120 TI - [Apolipoprotein A-IV and transportation of cholesterol from smooth muscle cells in experimental hyperlipidemia]. AB - The effects of apolipoprotein (apo) A-IV and apoA-IV/phosphatidylcholine (PC) liposome on cholesterol efflux from the smooth muscle cells originating from the aorta of hypercholesterolemic rabbit model and control rabbits, and on the activation of lecithin cholesterol acyltransferase (LCAT) were studied respectively. Both apoA-IV/PC and apoA-I/PC liposomes have similar efficiency as the HDL's, i.e. a strong ability to clear intracellular cholesterol and the ability to activate LCAT. There were no differences noticed on the clearance ability between apoA-IV and apoA-I or between apoA-IV/PC and apoA-I/PC liposomes. These results suggest that apoA-IV may play an important role in the process of reverse cholesterol transport and apoA-IV/PC liposome may be effectively used instead of natural HDL to prevent the development of atherosclerosis. PMID- 7781122 TI - [Isolation and identification of enteric adenovirus in China]. AB - Enteric adenovirus type 40/41 is considered to be the second major cause of gastroenteritis in young children. In this study fecal specimens 86-123 from diarrhea patients were isolated and examined in Grahm 293 cells. This induced cytopathic effect (CPE) at this cells. Viral particles were also found in fecal specimens and by electron microscopy. Examination of the isolate with Cambridge Biotech Adenoclone-Type 40/41 test kit indicated that it contained EAd. On the basis of the above studies, one strain of EAd was the first isolated virus in China. PMID- 7781123 TI - [Photorefractive keratectomy for myopia: 6 month results]. AB - The argon fluoride excimer laser is able to ablate the superficial cornea and to correct refractive problems. Photorefractive keratectomy (PRK) was performed on 103 myopic eyes ranging from -0.75D to -6.00D. We prospectively evaluated visual and refractive results that were followed for more than 6 months. Uncorrected visual acuity of 1.0 or better was achieved in 88.35%. The difference between attempted and achieved refractive correction was within +/- 1.00D in 94.17%. 10 eyes (9.71%) had trace to mild subepithelial hare and 19 eyes (18.45%) had loss of one line of best spectacle corrected visual acuity. The excimer laser PRK appears to be a predictable and effective method to correct myopia under -6.00D. PMID- 7781121 TI - [Effect of NMBzA on the oncogene and multiple tumor suppressor genes in monkey esophageal epithelium]. AB - Mutations of ras oncogene and multiple tumor suppressor genes p53, Rb and APC in esophageal epithelium of rhesus monkey fed with one dose of N-methyl-N benzylnitrosamine (NMBzA 30mg/kg), which was found in high incidence areas of esophageal cancer in China, were analysed by PCR and direct sequencing. Mutation at codon 12 of Ha-ras gene was not found in esophageal epithelium of monkey fed with NMBzA. Some mutations of p53 gene were found in esophageal epithelium of monkey after being fed with NMBzA for 24-48 hours. Some mutation of Rb and APC were found in esophageal epithelium of monkey after being fed with NMBzA for 48 hours. The mutation fingerprints of these genes disappeared in esophageal epithelium of monkey after being fed with NMBzA for 5 days. The results demonstrated that chemical carcinogen NMBzA can induce mutations of multiple tumor suppressor genes in monkey (in vivo) and indicated that the alteration of tumor suppressor genes in the initial stage of carcinogenesis needs many hits by chemical carcinogen. These alterations of p53, Rb, APC genes were similar to the changes of these genes in some reported previously primary esophageal cancer. PMID- 7781125 TI - [Oscillatory potentials in retinitis pigmentosa with TCM treatment]. AB - Computer-averaged oscillatory potentials (OPs) of electroretinogram (ERG) were recorded in 54 patients affected by different hereditary forms of retinitis pigmentosa (RP) before and after three-months of traditional Chinese medicine (TCM). This study was conducted in order to investigate the alterations of physiological function in inner part of the retina affected by RP. The results showed that OP waveforms were recordable in 22 and 27 patients before and after TCM treatment, respectively. The amplitudes of summed OPs (sigma OPs) were increased significantly in patients with different hereditary modes of RP, and also in those by clinical TCM classification after the treatment. The component specific amplitudes of OPs were observed. In particular, OP2 showed an elevation in both dominant and nondominant patient groups, while OP3 only showed an elevation in the dominant group. The results suggest that OP2, which represents mainly cone OP activity, could be improved in the patients extensively; and OP3, which represents mainly rod OP activity, could be improved only in the patients with less advanced retinal degeneration. These data provide evidence that visual function in the inner retina of patient with RP could be improved to a certain extent with TCM treatment. PMID- 7781124 TI - [Apoptosis of mouse MS-2 fibrosarcoma cells induced by photodynamic therapy with LDL-administered zinc-phthalocyanine]. AB - Photodynamic destruction of MS-2 fibrosarcoma cells in mice induced by LDL administered Zinc-phthalocyanine and red light irradiation was studied by electron microscopy. The pronounced structural changes such as chromatin condensation, disappearance of nuclear pores, karyopyknosis, karyorrhexis, leakage of chromatin aggregates, autophagocytosis, bleb formation on the cell surface, cytoplasmic vacuolization and cell fragmentation suggest that the tumor cell death was induced by apoptosis. However, its exact mechanism and regulating pathways remain to be further investigated. PMID- 7781126 TI - [High purification of human thrombin]. AB - A highly purified human thrombin was prepared from plasma. The procedure involved the adsorption of prothrombin from human plasma by barium chloride and precipitation by using ammonium sulfate. The partially purified prothrombin was activated by tissue thromboplastin and followed by chromatography on Amberllte and SP-Sephadex. The purified enzyme is homogeneous on SDS-PAGE and has a specific activity toward fibrinogen of 2000 NIH U/mg. The recovery is about 30% approximately 40%. This highly purified human thrombin can be used as a tool enzyme in the downstream procedure of fused recombinant proteins expressed by genetic engineering. PMID- 7781127 TI - [Inhibitory effect of anti-motoneuron serum on the neurite outgrowth of spinal cord explants (in vitro) and the cross-reactivity of serum to human and rat motoneurons]. AB - The effects of rabbit anti-swine motoneuron serum (RAS), normal rabbit serum (NRS), skeletal muscle extracts (MET, 50 and 100 micrograms/ml) and brain extracts (BET, 50 and 100 micrograms/ml) on neurite outgrowth of neonatal rat spinal cord explants (in vitro) were studied after 5 days of treatment. In comparison with NRS (explants possessing neurite outgrowth accounted for 36.7%, n = 30), the neurite outgrowth of spinal cord explants was significantly accelerated by MET (96.7% of explants had neurite outgrowth), but inhibited by RAS (only 13.3% of the explants had neurite outgrowth). The cross-reactivity of RAS to the spinal motoneuron of swine, humans and rats were also demonstrated by immunocytochemical techniques. PMID- 7781129 TI - [Establishment of a human fetal thymocyte cell line and observation of its biological properties]. AB - Thymocytes were isolated from a five month fetus after caesarean section and cultured in vitro. A cell line named human fetal thymocyte 8810 (HFT8810) was established and cultured continuously for 2 years in our lab, and grew well after recovery from the state of being frozen in liquid nitrogen. The HFT 8810 cells retained their ability to secrete thymosin after many generations in vitro culture. PMID- 7781128 TI - [Detection of hypermethylation in affected males with fragile X syndrome by PCR assay]. AB - PCR technique was applied to detect hypermethylation at BssH II recognition sites within CpG island of FMR-1 gene in normal, affected, and clinically suspected males with fragile X syndrome. Hypermethylation was found to occur in all 7 affected and 5 of 26 suspected, but none of 15 normal males. The results of PCR assay are in good coincidence with those of Southern blot and cytogenetic assays. This PCR assay will be a promising method in the diagnosis of fragile X syndrome in males with mental retardation. PMID- 7781130 TI - [Use of high-performance liquid chromatography electrochemical detection to detect hydroxy radicals]. PMID- 7781131 TI - [Clinical observation of labor of induction with nutritional food]. AB - 386 pregnant women in 3rd trimester having indications of induction labor were induced with nutritional food. The success rate was 77.92% (301/386) and correlated with the cervical Bishop score. Furthermore the success rate increased significantly in term with premature rupture of the membrane (90.54%). This method, which was found to be safe and effective can significantly shorten the first and total stage of labor. PMID- 7781132 TI - [Flow cytometry used to distinguish between complete and partial hydatidiform moles]. AB - The nuclear ploidy of 14 placentas was determined by flow cytometry. All histologically classified complete moles (4 cases), hydropic villi (4 cases) and control placentas (3 cases) were diploid; whereas two of three histologically classified partial moles were triploid. The remaining case classified as partial mole was diploid, most likely a complete mole. It was concluded that DNA flow cytometric analysis offers an informative supplement to the histological interpretation of hydropic placentas. PMID- 7781133 TI - [Experimental study on acute hypoxia in newborn rabbits]. AB - To investigate the hypoxic-ischemic damage of perinatal asphyxia, the acute hypoxic models of newborn rabbits were established and the effects of ligustrazine and anisodamine on pulmonary arterial pressure (PAP), dural blood flow (DBF) and blood gas of the hypoxia rabbits were observed. Acute hypoxia was caused by inhalation of 10% O2 + 90% N2 mixture. PaO2 was obviously reduced, PAP and DBF were obviously increased. But PAP in ligustrazine group did not increase and the elevated level of PAP in the anisodamine group was lower than the control. DBF and PaO2 was not affected by using both of the drugs. Ligustrazine and anisodamine might be effective for preventing and treating newborn persistent pulmonary hypertension. PMID- 7781134 TI - [Patella resurfacing and patellofemoral resurfacing]. AB - Since 1983 isolated polyethylene patellar prosthesis was used for patella resurfacing of 19 patients with patellofemoral osteoarthritis. After an average of 44.9 months follow-up, the treatment was found to be not as satisfactory as earlier trials. The main reason was the wide erosion of femoral condyle caused by the polyethylene patella. To overcome this shortness, a new type of patellofemoral prosthesis was designed by the authors, which was named Y-L-Q. From January, 1991 to November, 1993, this prosthesis was used to treat 16 knees of 13 patients with patellofemoral osteoarthritis. Most of those patients improved both symptomatically and functionally. The good to excellent results rate was 87.5% (14/16 knees) at the time of an average 10 month follow-up. The early results of our experience with patellofemoral resurfacing are encouraging, and extended follow-ups are in progress. PMID- 7781135 TI - [Recent advances in the screening of target genes with monoclonal antibody probes]. PMID- 7781136 TI - Fludarabine- and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event. AB - The nucleoside analogs fludarabine and gemcitabine inhibit cellular DNA synthesis by two different mechanisms: (1) direct termination of DNA strand elongation after the triphosphate of each drug is incorporation into DNA; and (2) indirect inhibition of DNA synthesis by decreasing cellular dNTPs through inhibition of ribonucleotide reductase. The present study demonstrated that incorporation of the analogs into DNA is critical for the cytotoxic action of these drugs in human T lymphoblastoid CEM cells. S phase cells, which actively incorporated the analogs into DNA, were most sensitive to the cytotoxic action of these compounds. A relatively short-term (5-24 h) cessation of cellular DNA synthesis without analog incorporation was not sufficient to cause cell death. The drug-treated cells died through apoptosis characterized by generation of internucleosomal DNA fragmentation and apoptotic morphology. Induction of high molecular mass (50-500 kb) DNA fragmentation was also observed in cells undergoing apoptosis; this type of DNA degradation was strongly correlated with the analog-induced cell death process. Inhibition of the analog incorporation into DNA by aphidicolin blocked both types of DNA fragmentation and apoptotic morphology, indicating the essential role of analog incorporation into DNA in drug-induced cell death. PMID- 7781137 TI - Phase I study of NKT-01. AB - A phase I study of NKT-01 (deoxyspergualin), which is a derivative of an antitumor antibiotic, spergualin, was performed by a cooperative study group. NKT 01 was given intravenously by 3-h infusion. The effect of single administration was studied prior to evaluation of daily administration for 5 consecutive days. In all, 5 and 33 patients with various malignancies, including leukemia, were entered into the trials of single and daily administration, respectively. In the single-administration study, all patients were evaluable and no clear adverse effect was observed at doses ranging from 20 to 320 mg/m2. In the daily administration study, 28 evaluable patients (16 men and 12 women; median age, 55.5 years) were treated with a daily dose of 20-500 mg/m2. Toxicities such as myelosuppression, mild nausea/vomiting, anorexia, alopecia, tongue and perioral numbness, and hypotension were observed dose-dependently during or after the treatment. Grade 2 leukopenia, thrombocytopenia, and anemia were experienced at a dose of 500 mg/m2. These usually recovered to normal values by approximately 3 weeks after treatment. A pharmacokinetic analysis of single administration revealed rapid plasma clearance, with mean half-lives for the alpha and beta phases being 28 min and 6.9 h, respectively. Approximately 12% of the infused dose was excreted into the urine in unmetabolized form. The pharmacokinetic parameters obtained after 5-day administration were similar to those recorded after single administration. Concerning treatment response, a transient but significant reduction in the number of leukemic cells was observed in one patient with adult T-cell leukemia. In this study, perioral numbness, hypotension, and hematological toxicity were concluded to be dose-limiting, with the maximal acceptable dose being 500 mg/m2. The recommended dose for a phase II study of NKT 01 against solid tumors was judged to be 400 mg/m2 given daily by 3-h infusion for 5 days, every 3 weeks. In hematological malignancies, however, higher myelosuppressive schedules of administration should be investigated. PMID- 7781138 TI - In vitro activity of S 9788 on a multidrug-resistant leukemic cell line and on normal hematopoietic cells-reversal of multidrug resistance by sera from phase I treated patients. AB - The triazinoaminopiperidine derivative S 9788 is a new multidrug-resistance modulator that is currently being evaluated in phase I clinical trials. In this study, the reversal effect of S 9788 in comparison with verapamil was shown in vitro in human T-leukemic CCRF-CEM/VLB cells expressing the multidrug-resistance (MDR) phenotype. S 9788 increased in a dose-dependent manner the cytotoxic activity of doxorubicin or vinblastine, with complete reversal of resistance occurring at 2 microM for a concomitant continuous exposure (96 h) to the cytotoxic drugs. At respective concentrations equivalent to the IC10 value (the concentration inhibiting 10% of cell growth), S 9788 was 44 times more potent than verapamil in CCRF-CEM/VLB cells. S 9788 at 2 microM did not enhance the in vitro toxicity of doxorubicin or vinblastine in the human normal bone-marrow erythroid (BFU-E) and myeloid (CFU-GM) progenitors. The effect of exposure duration and concentrations on the synergistic action of modulator and cytotoxic agent closely depended on the cytotoxic agent studied. Post-incubations with S 9788 alone after a 1-h coadministration with vinblastine and S 9788 dramatically increased the reversal effect (4-41 times) in proportion to both the duration of postincubation and the concentration of S 9788. In contrast, for doxorubicin resistance, post-incubation with S 9788 alone induced a maximal 2-fold increase in the reversal effect that was not proportional to the post-incubation duration. In patients treated with S 9788 as a 30-min intravenous infusion during phase I trials, a good correlation was found between the serum levels of S 9788 and the ability to reverse MDR in CCRF-CEM/VLB cells. The reversal effect was dose dependent and was effective beginning at a plasma concentration of 0.25 microM. These data form a basis for the design of phase II trials using a combination of a loading dose of S 9788 given before vinblastine or doxorubicin administration followed by a maintenance infusion of S 9788 alone for a period of 2-24 h. PMID- 7781139 TI - Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies. AB - Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose provided relatively little clinical benefit for patients with refractory leukemia. The dose-limiting toxicity is CNS toxicity with increasingly severe encephalopathy at doses > or = 640 mg/m2. It would be reasonable to investigate further dose escalation of hepsulfam in a divided dose schedule to minimize the peak concentrations which may be related to the encephalopathy. EEG monitoring is recommended for early detection of slowing of alpha rhythm waves. Hematopoietic stem cell support will probably be required at total doses exceeding 800 mg/m2. PMID- 7781140 TI - Safety and efficacy of intraperitoneal injection of etoposide in oil suspension in mice with peritoneal carcinomatosis. AB - We compared the safety and efficacy in mice with peritoneal carcinomatosis of two etoposide formulations: an aqueous solution (Etp-sol) and particles suspended in oil (the addition products of iodine and the ethyl esters of the fatty acids obtained from poppy-seed oil (Lipiodol) or sesame oil; Etp-oil). We also investigated tissue distribution of etoposide in rats treated with Etp-oil and Etp-sol. Etoposide was injected intraperitoneally at concentrations ranging from 52 to 392 mg/kg (increasing geometrically by a factor of 1.4). The 50% lethal dose (LD50), determined over a 2-week period of observation, was 135 mg/kg for Etp-oil and 108 mg/kg for Etp-sol. Autopsy findings included macroscopic intestinal bleeding, necrosis of the intestinal mucosa, and pulmonary congestion in mice from both treatment groups. In the efficacy trials. 10(6) P388 leukemia cells were transplanted into CDF1 male mice, and Etp-oil and Etp-sol were injected at doses of 20 mg/kg and 80 mg/kg. In the groups receiving the 20 mg/kg dose, 11 of 19 mice in the Etp-oil group survived to day 60 compared with 3 of 20 mice in the Etp-sol group. Toxicity-related deaths occurred in 1 of 20 mice treated with 80 mg/kg Etp-oil and in 8 of 20 mice treated with 80 mg/kg Etp-sol. No cancer-related deaths were associated with the 80 mg/kg dose in either treatment group. Our findings showed that the Etp-oil was associated with a lower toxicity and a higher efficacy than the Etp-sol. To evaluate tissue distribution, rats were injected intraperitoneally with 5 mg/kg body weight of Etp-sol or Etp oil. The tissue distribution of etoposide was subsequently analyzed by high performance liquid chromatography. Compared with Etp-sol, Etp-oil delivered significantly greater amounts of etoposide and for a longer period to the omentum, taken as representative of the intraperitoneal tissue, and the etoposide concentration in blood plasma was increased more slowly and decreased more gradually. PMID- 7781142 TI - Comparative resistance of idarubicin, doxorubicin and their C-13 alcohol metabolites in human MDR1 transfected NIH-3T3 cells. AB - The anthracycline analog idarubicin (ID) is useful in the treatment of leukemias, and is of further interest because of the unique activity of its major circulating metabolite idarubicinol (IDOL). In vitro studies have shown that ID retains activity against tumor cells made resistant by prolonged exposure to substrates of the p-glycoprotein energy-dependent efflux pump. To selectively investigate multidrug resistance to ID in tumor cells, ID, IDOL, doxorubicin (DX) and doxorubicinol (DXOL) were evaluated for growth inhibitory activity when incubated with NIH-MDR1-G185 (MDR) cells or with the parent NIH-3T3 (3T3) cells. The MDR cells are transfected with the human multidrug gene mdr1, and express a functional p-glycoprotein. ID growth inhibitory activity was much less affected by p-glycoprotein-mediated efflux than was DX. ID IC50 values were only 1.8-fold greater in the MDR cell line than in the parental 3T3 cell line, while the IC50 value for DX was 12.3-fold greater in the transfected cell line. Verapamil (VRP) fully restored drug sensitivity of the MDR cell line to ID and DX. In studies with the alcohol metabolites, IDOL and DXOL IC50 values were 7.8- and 18.9-fold greater, respectively, for the MDR cell line than for the parental cell line. Intracellular concentrations of DX and DXOL, but not ID and IDOL, were substantially increased in the MDR cells when VRP was present in the incubation mixtures. ID and IDOL retain substantial growth inhibitory activity in mdr1 transfected cells, and ID may be of value in clinical settings where multidrug resistance mediated by p-glycoprotein is a potential limitation of therapy. PMID- 7781141 TI - Antitumor activity of FCE 26644 a new growth-factor complexing molecule. AB - FCE 26644, or 7,7'-(carbonyl-bis[imino-N-methyl-4, 2 pyrrole carbonyl-imino(N methyl-4,2-pyrrole)carbonyl-imino])-bis-(1,3- naphthalene)disulfonic acid, belongs to the newly synthesized class of sulfonated derivatives of distamycin A. FCE 26644 is a noncytotoxic molecule capable of inhibiting the binding of basic fibreblast growth factor (bFGF), platelet-derived growth factor (PDGF beta) and interleukin 1 (IL-7) to their receptors and to block bFGF-induced vascularization in vivo as well as neovascularization in the chorioallantoic membrane. FCE 26644 and suramin, a compound possessing the same terminal half-life (t1/2) in mice and, presumably, the same mode of action, inhibit the growth of solid murine tumors, M5076 reticulosarcoma, and MXT and S180 fibrosarcoma and are inactive against B16F10 melanoma. The activity of FCE 26644 was constantly observed at nontoxic doses, at variance with suramin. FCE 26644 was also found to maintain activity against M5076 resistant to cyclophosphamide and to be equally active against UV 2237 and UV 2237/ADR fibrosarcoma. PMID- 7781143 TI - Pretreatment H2 receptor antagonists that differ in P450 modulation activity: comparative effects on paclitaxel clearance rates and neutropenia. AB - Histamine-2 receptor antagonists (H2RAs) are principal components of the premedication regimen used to prevent major hypersensitivity reactions in patients receiving paclitaxel. Several different H2RAs, including cimetidine, ranitidine and famotidine, have been used in clinical trials of paclitaxel, as well as by clinicians in different geographic regions and hospitals primarily because of differences in the availability of the various H2RAs. However, H2RAs have highly variable cytochrome P450-modulating capabilities, and the P450 system appears to play a major role in paclitaxel metabolism and disposition. Therefore, the use of different H2RAs may result in different pharmacologic, toxicologic and antitumor profiles due to differential effects on paclitaxel metabolism. This study evaluated whether cimetidine and famotidine, which possess disparate P450 modulating capabilities, differentially affect paclitaxel clearance rates and the agent's principal toxicity, neutropenia. Women with advanced, platinum-refractory ovarian carcinoma received two courses of treatment with 135 mg/m2 paclitaxel over 24 h while participating in the National Cancer Institute's Treatment Referral Center Protocol. A crossover design was employed in which consecutive patients received either 300 mg cimetidine i.v. or 20 mg famotidine i.v. before their first course of paclitaxel and the alternate H2RA before their second course. In order to evaluate the differential effects of cimetidine and famotidine on pertinent pharmacologic and toxicologic parameters in the same individual, paclitaxel concentrations at steady-state (Css), paclitaxel clearance rates, and absolute neutrophil counts (ANCs) were obtained during both courses. Paclitaxel Css values were not significantly different in individual patients when either cimetidine or famotidine preceded paclitaxel (p = 0.16). Mean paclitaxel clearance rates were 271 and 243 ml/min per m2 following cimetidine and famotidine, respectively. These clearance rates were not significantly different in paired analysis (p = 0.30). The likelihood of subsequently requiring granulocyte-colony stimulating factor (G-CSF) for severe neutropenia during course 1 did not differ significantly between the two H2RAs (p = 0.9). Among patients who did not require G-CSF, mean percentage decreases in ANC were 87.7% and 84.2% after paclitaxel cycles preceded by cimetidine and famotidine, respectively. These measures of neutropenia did not differ significantly in paired analysis (p = 0.13). These results show that the H2RAs cimetidine and famotidine do not differentially affect the pharmacologic and toxicity profiles of paclitaxel when used in the premediation regimen to prevent major hypersensitivity reactions, and may be interchanged. PMID- 7781144 TI - A limited sampling strategy for the study of pirarubicin pharmacokinetics in humans. AB - Pirarubicin (4'-O-tetrahydropyranyldoxorubicin, THP-Adriamycin) is a new anthracycline antibiotic that has recently been developed because its reduced cardiac toxicity is associated with an antitumour efficacy similar to that of doxorubicin. Pirarubicin is characterised by strong haematological toxicity, which has been shown to be correlated with pharmacokinetic parameters, especially the area under the time-concentration curve. To obtain routine pharmacokinetic evaluations of pirarubicin for dose monitoring we developed a limited sampling strategy relying on three blood samples taken at the end of the infusion and at 12 and 24 h post-infusion. The characteristics of interindividual variability were assessed on the first courses of treatment performed in 18 patients; the model was then validated on 10 independent first courses of treatment performed in 10 other patients. The main pharmacokinetic parameters (half-lives, total volume of distribution, total plasma clearance) were estimated in the test group by maximum-likelihood estimation using all samples and by Bayesian estimation using three samples. The concordance between the two estimates was correct (the bias and precision for clearance were 2.3% and 12.1%, respectively), which shows that this limited sampling strategy can be used in routine drug monitoring. PMID- 7781145 TI - Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics. AB - The pharmacokinetic monitoring of anthracycline-containing regimens is warranted because of the important toxicity of these drugs and because pharmacokinetic pharmacodynamic relationships have been clearly established. We studied the pharmacokinetics of the new anthracycline pirarubicin in 80 courses of treatment performed in 27 patients, using a limited sampling protocol we had previously validated. We observed (for 47 of these courses) a significant correlation between the leucocyte cell kill and the pirarubicin area under the time x concentration curve, but the most significant correlation was obtained using the plasma concentration of doxorubicin, a metabolite of pirarubicin, at the end of the infusion. On the basis of this value, it is possible to predict for pirarubicin haematological toxicity in a way that can help the clinician in identifying patients at risk for toxicity. PMID- 7781146 TI - Experimental solid tumour activity of N-[2-(dimethylamino)ethyl]-acridine-4 carboxamide. AB - N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (DACA), a DNA intercalator that exerts its antitumour action through the enzyme topoisomerase II, has previously been shown to be curative against the transplantable Lewis lung adenocarcinoma growing as lung tumour nodules in mice. On the basis of this finding as well as its high in vitro activity against multidrug-resistant cell lines, DACA has been chosen for clinical trial under the auspices of the Cancer Research Campaign, United Kingdom. In the present study the activity of DACA was assessed against advanced (5-mm diameter) s.c. colon 38 adenocarcinomas in BDF1 mice using tumour growth delay as an end point. Its activity was found to be related positively to the total dose given and negatively to the total duration of the dose schedule. Adoption of a split-dose i.p. administration schedule or slow i.v. infusion allowed the administration of large doses without toxicity. The activity of DACA was comparable with that of 5-fluorouracil and superior to that of doxorubicin, cyclophosphamide and the experimental amsacrine analogue CI-921. Mitoxantrone, amsacrine, etoposide, teniposide and daunorubicin showed minimal activity. DACA also demonstrated significant activity against the NZM3 melanoma human cell line growing as a xenograft in athymic mice. PMID- 7781147 TI - The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post menopausal breast cancer patients. AB - This study investigated the influence of the aromatase inhibitor 4 hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E2) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E2 was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3% +/- 9.5%, 70.0% +/- 5.1% and 57.3% +/- 5.3%, respectively (mean +/- SEM). Corresponding values for plasma E2 suppression were 30.7% +/- 6.5%, 43.4% +/- 4.5% and 42.9% +/- 6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E2 levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E2 suppression was observed. The suppression of E2 by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition. PMID- 7781148 TI - Treatment of advanced gastric cancer with the combination fluorouracil, leucovorin, etoposide, and cisplatin: a phase II study of the ONCOPAZ Cooperative Group. AB - A phase II study was performed to assess the efficacy and toxicity of the combination of 5-fluorouracil (5-FU), leucovorin (LV), etoposide, and cisplatin (FLEP) in patients with advanced gastric carcinoma. A total of 46 consecutive, previously untreated patients with unresectable, measurable gastric carcinoma were treated with 300 mg/m2 LV, 100 mg/m2 etoposide, 500 mg/m2 5-FU, and 30 mg/m2 cisplatin on days 1-3 every 28 days. All courses were given on an outpatient basis. A total of 169 courses of treatment were given. In all, 18 of the 46 patients (39%) had an objective response [95% confidence interval (CI), 25%-54%] and 2 (4%) patients experienced a clinical complete response. The median duration of response was 5 months. The main side effects were hematological and gastrointestinal. Grade 3-4 toxicity was encountered as follows: leukopenia, in 9.5% of the courses; anemia, in 3%; thrombocytopenia, in 3%; nausea/vomiting, in 4%; and diarrhea, in 5%. Hospitalization due to fever and granulocytopenia was required in 5 patients, 3 of whom died of sepsis. In conclusion, FLEP shows moderate activity in patients with advanced gastric carcinoma, albeit at the cost of a high degree of toxicity. For this reason we do not recommend its use. PMID- 7781149 TI - Oral trofosfamide: an active drug in the treatment of soft-tissue sarcoma. AB - A total of 23 patients with metastatic sarcomas were treated with continuous oral trofosfamide, an alkylating agent structurally related to cyclophosphamide and ifosfamide. In all, 12 of the patients were chemotherapy-naive. Doses were escalated every 3rd week until the development of leukopenia of WHO grade 2. The treatment was well tolerated and produced little subjective toxicity. Leukopenia was the dose-limiting toxicity. The daily dose that produced grade 2 leukopenia was 200-250 mg in 65% of the patients. Three patients responded, all of whom had been treated with trofosfamide as first-line treatment. PMID- 7781150 TI - Development and validation of a sensitive solid-phase-extraction and high performance liquid chromatography assay for the bioreductive agent tirapazamine and its major metabolites in mouse and human plasma for pharmacokinetically guided dose escalation. AB - A sensitive solid-phase-extraction and high-performance liquid chromatography (HPLC) method has been developed to investigate the pharmacokinetics and metabolism of the hypoxic-cell cytotoxic agent tirapazamine (1,2,4-benzotriazine 3-amine 1,4-di-N-oxide; WIN 59075, SR 4233), currently in phase I/II studies in the United Kingdom and United States. A sample extraction and concentration process was devised using strong cation-exchange Bond Elut cartridges. Tirapazamine, the mono and zero-N-oxide metabolites (WIN 64012, WIN 60109) were isocratically resolved using a microBondapak phenyl HPLC column and measured using photodiode-array detection. The minimal quantifiable level (MQL) of tirapazamine was 40 ng/ml in mouse plasma and 20 ng/ml in human plasma. Recovery was consistently greater than 80% for all compounds over the concentration range of 20 ng/ml to 20 micrograms/ml. No significant decomposition was observed following up to three freeze/thaw cycles and storage at -70 degrees C for 52 days. The assay was accurate and reproducible, with measured values lying within the limits of defined acceptance criteria. Additional studies to investigate the degree of plasma protein binding showed that tirapazamine did not bind extensively to plasma proteins (binding, 9.7% +/- 0.1% and 18.7% +/- 1.3% in mouse and human plasma, respectively). These small species differences in protein binding are unlikely to have any major impact on the extrapolation of pharmacokinetic data from mice to humans. The assay has now been successfully applied to investigate the pharmacokinetics and metabolism of tirapazamine in mice and patients as part of a pharmacokinetically guided dose-escalation strategy for phase I clinical trials. PMID- 7781151 TI - Usher syndrome: increasing awareness in Scotland. AB - In July 1993, professionals from a number of European countries met at the 7th European Usher Syndrome Study Group. The purpose of the Study Group (which meets on a biannual basis) is to give professionals working in this specialized field the opportunity to share ideas and examples of their work. People attending included medical practitioners, social service workers, representatives from voluntary bodies and individuals with Usher. The following article is an expanded version of a paper presented at the Study Group. It describes the development of a 3 hour workshop for the wide range of practitioners a child or young person with Usher syndrome may meet. Through group work, positive approaches to working through the personal and practical implications of Usher syndrome are explored. PMID- 7781152 TI - Language and motor development in pre-term children: some questions. AB - A cohort of 37 pre-term children was assessed for both morphosyntactical and for vocabulary skills at the age of 2 and again at the age of 3 years and 6 months. They were compared with two comparison groups of full-term children (adjusted age and chronological age). The results indicated (1) a clear asynchrony between the two components of language production assessed at both ages, (2) an accurate prediction of language delay at age 2 for pre-term children (35% of pre-term children were detected for morphosyntax as measured by Mean Length of Utterance and 27% of pre-term children were detected for vocabulary as measured by the number of different words) and, (3) no evidence on the relationship of language and motor development as measured by formal tests. Such findings strongly challenge the validity of standardized developmental tests and support to a certain extent the hypothesis that language development is independent of motor skills. A neurodevelopmental assessment is suggested. PMID- 7781153 TI - Parents, partnership and education officers: a study of attributions. AB - Thirty-five parents of children with special educational needs were interviewed to ascertain their experiences of dealing with education officers involved in the assessment and placement of their children. They were found predominantly to make internal attributions for negative behaviours, and external attributions for positive behaviours. The implication of these results for new United Kingdom government initiatives to reduce conflict between parents and education authorities are examined. PMID- 7781154 TI - Children in medical research: Australian ethical standards. AB - This paper examines standards for the use of children as research participants in medical research which are relevant to Australia and relates the standards to pivotal ethical issues. The standards include the National Health and Medical Research Council's NHMRC Statement and Supplementary Notes, professional codes of ethics, international human rights conventions, United Kingdom and United States codes of ethics, and statute and case law. The key ethical issues of potential risk and benefit to the child, and consent to research participation are discussed. Suggestions for the improvement of the NHMRC Statement are made. PMID- 7781155 TI - The development of communication in blind and in deaf infants--similarities and differences. AB - Results from two longitudinal studies of blind infant--sighted mother and of deaf infant-hearing mother/deaf mother interaction, are summarized in this paper. The aim is to shed light on the role of visual and auditory stimulation in the development of communication. Video-recorded interactions taken during infancy were transcribed in a systematic, objective and detailed way. The development of communication is described with a focus on pre-verbal abilities, exploration of toys, social and symbolic play, communicative intent and sharing of experiences. The results show a delay in the development of communication in the blind infants compared with the deaf infants, indicating a more critical role of visual stimulation compared with auditory stimulation during the infancy period to this development. PMID- 7781156 TI - Alterations in responsiveness to ethanol and neurotrophic substances in fetal septohippocampal neurons following chronic prenatal ethanol exposure. AB - Pregnant Long-Evans rats were maintained on three diets: a liquid diet in which ethanol accounted for 35-39% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, and a lab chow control diet. At gestation day 18, the fetuses were taken and cultures of septal and hippocampal neurons prepared. Neuronal survival and neurite outgrowth were compared in cultures from the three diet groups, using the following media supplements: ethanol (1.2, 1.8 or 2.4 g/dl), neurotrophic factors (nerve growth factor [NGF] with the septal cultures, basic fibroblast growth factor [bFGF] with the hippocampal cultures), or ethanol plus neurotrophic factors. Both the septal and hippocampal neurons responded to ethanol in a dose-dependent manner. The neurons from both populations from fetuses which had been exposed prenatally to ethanol, however, tolerated considerably higher ethanol concentrations before decreases in survival or outgrowth were seen. These ethanol-exposed neuronal populations were also less responsive to neurotrophic factors: in hippocampal cultures, process outgrowth was significantly enhanced by bFGF in control but not ethanol-derived cultures, and in septal and hippocampal cultures, the neurotrophic factors significantly ameliorated ethanol neurotoxicity in control cultures, but not in those from the ethanol-exposed fetuses. The possible relevance of these observations to the fetal alcohol syndrome is discussed. PMID- 7781157 TI - Postnatal development of inositol 1,4,5-trisphosphate receptors: a disparity with protein kinase C. AB - Ligand-stimulated phosphoinositide hydrolysis activates a bifurcating second messenger system, releasing inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG), which activates protein kinase C (PKC). Yet, in developing cat visual cortex and hippocampus, high levels of [3H]PDBu binding (labelling PKC) appear much earlier than do [3H]IP3 labelled sites. Binding distributions for the two ligands also appear to be complimentary in both brain regions. Moreover, early surgical removal of input to the visual cortex increases [3H]PDBu binding without affecting that of [3H]IP3. Our results suggest that, (1) at certain developmental stages, IP3 and PKC may act individually or complimentarily rather than synergistically in the visual cortex and hippocampus; (2) in neonatal cortex, IP3 metabolites rather than IP3 itself may act as second messengers; (3) although both IP3 receptors and PKC are localized in intracortical cells, their expression is regulated by different mechanisms during development. PMID- 7781158 TI - The intensity of a fetal taste aversion is modulated by the anesthesia used during conditioning. AB - Rat fetuses (E18) can learn a taste aversion in utero if experience with a sweet flavor (saccharin = Sac) is followed by a malaise-producing injection of lithium chloride (LiCl). Here we report that this phenomenon can be significantly modulated by the type of anesthesia administered to the pregnant dam before the conditioning procedure. Dams were anesthetized with one of the following drugs or drug combinations: (1) sodium pentobarbital; (2) ketamine hydrochloride and xylazine; or (3) sodium pentobarbital and ketamine hydrochloride. While under the influence of these anesthetics, rat fetuses received pairings of Sac + LiCl or one of the following sets of oral and systemic (i.p.) control injections: Sac + Saline, H2O + LiCl; H2O + Saline. At age 15 days neonatal rats were given a taste preference test by allowing them to select nipples painted with either saccharin or vehicle (H2O). After weaning, rats were given an additional taste preference test where they were allowed to drink from bottles filled with either 0.30% saccharin or water. Neonates that received Sac + LiCl injections avoided saccharin-painted nipples while neonates that received control injections in utero preferred saccharin-painted nipples. Rats that acquired the taste aversion under the influence of ketamine showed a significantly stronger conditioned taste aversion on the nipple preference test than did those from dams injected with sodium pentobarbital. The conditioned taste aversion was not detectable later during the bottle preference test. Since ketamine blocks N-methyl-D-aspartate (NMDA) glutamate receptors, and these receptors have been implicated in neural plasticity during development, our data suggest that NMDA antagonism can potentiate fetal learning. Ketamine has been used as an obstetrical and pediatric anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781159 TI - Effects of chronic activation of dopamine D-2 receptors in cultures of rat fetal dopaminergic neurons: indications for alterations in functional activity. AB - In Parkinsonian patients, previously subjected to neuronal grafting therapy, the survival and functional status of dopaminergic grafts might be impaired by the concurrent pharmacotherapy with L-DOPA and/or dopamine (DA) D-2 receptor agonists. To test this hypothesis in vitro, we studied the effects of chronic DA D-2 receptor activation on the functional capacity of cultured fetal rat mesencephalic DA neurons, using the activity of tyrosine hydroxylase (TH) and the intracellular dopamine content as neurochemical parameters. In cellular extracts prepared from our cultures, TH activity (as determined by the release of 3H2O from 3H-[3,5] tyrosine) appeared to be tetrahydrobiopterin-, Fe2+, and temperature sensitive, while in intact cells, the catalytic activity of TH could be induced by K(+)-evoked depolarization in a Ca(2+)-dependent way. In contrast, no acute DA D-2 receptor mediated inhibitory effects could be demonstrated in intact cells, either when tested under basal or depolarizing conditions. Nevertheless, after chronic exposure to DA D-2 receptor agonists for 14 days clear differences were observed in the functional status of cultured fetal dopaminergic neurons. Thus, whereas the overall survival and basal TH activity of cultured fetal dopaminergic neurons remained virtually unaltered, the depolarization induced activation of TH was enhanced in agonist-treated cultures. Moreover, after long-term treatment for 14 or 21 consecutive days, the intracellular DA content of agonist treated cultures appeared to be higher, as compared to untreated controls. It is concluded that chronic activation of DA D-2 receptors may induce adaptive alterations in the functional activity of cultured fetal dopaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781160 TI - Repeated intracerebroventricular administration of taurine lowers LH levels and postpones vaginal opening in peripubertal female rats. AB - We investigated the effect of repeated intracerebroventricular injections of taurine (Tau, 0.15 mumol/3 microliters distilled water), administered during postnatal days 23-29, on serum LH levels, and on the hypothalamic content of LHRH and amino acid neurotransmitters (measured by HPLC and electrochemical detection) in 30-day-old female rats (n = 18). Treatment with Tau lowered serum LH (Tau: 0.20 +/- 0.04; CONTROLS: 1.04 +/- 0.21 ng/ml RP3; mean +/- S.E.M.; P < 0.05) as well as hypothalamic LHRH levels (Tau: 82.6 +/- 9.5; controls: 128.7 +/- 14.1 pg/mg wet tissue, P < 0.05). Tau treatment doubled hypothalamic GABA levels (Tau: 31.3 +/- 2.9; CONTROLS: 15.6 +/- 1.2 nmoles/mg wet tissue, P < 0.001). In a second group of animals (n = 13), Tau treatment delayed vaginal opening by more than 2 days (P < 0.05 vs. controls). It is concluded that supplementation with Tau during the fourth postnatal week reduces LHRH/LH secretion and postpones sexual development, perhaps by increasing the activity of the hypothalamic GABAergic system. PMID- 7781161 TI - The developmental emergence of the representation of auditory azimuth in the external nucleus of the inferior colliculus of the guinea-pig: the effects of visual and auditory deprivation. AB - A topographic representation of the auditory azimuth has been described in the external nucleus of the inferior colliculus (ICX) of the guinea-pig [3]. This representation is characterized by directional multi-unit responses, at threshold stimulation intensities, with directional preferences organized in such a way as to represent the auditory azimuth along the rostro-caudal axis of the ICX. The following paper considers the emergence of that map and the role of developmental experience in its elaboration. Multi-unit responses to free-field broad-band auditory stimuli were recorded in the ICX. At threshold stimulation intensities, multi-unit receptive fields (MURFs) obtained from younger animals showed the same discrete spatial tuning as found in MURFs from animals older than 35 DAB (days after birth). However, a normal adult topographic representation was not present until animals were at least 30-32 DAB. Visual deprivation, by dark-rearing from birth until mapping (at 35-43 DAB), had no obvious detrimental effects on auditory receptive field size or topographic order in the ICX. Auditory deprivation was achieved by rearing animals in an environment of continuous omnidirectional noise from birth until mapping (47-53 DAB). Following auditory deprivation, receptive fields remained relatively discrete, but no correlation between rostro-caudal position of the recording site and the angle of the best response was observed. Thus, the representation of auditory azimuth in the ICX appears to be unperturbed by developmental visual deprivation but is susceptible to developmental auditory deprivation. PMID- 7781162 TI - Cyclic remodelling of growth cone lamellae and the effect of target tissue. AB - We report the existence of cyclical fluctuations in the total size of growth cone lamellae, represented by membrane protrusions and retractions, and show that aspects of this behavior can be regulated by the target tissue for the nerve fibers. The transition of the growth cone from a high to a less motile state, which occurs in the presence of the target tissue, has implications for the mechanisms that underlie nerve fiber elongation during development. PMID- 7781163 TI - Developmental change of mu opioid receptors in neonatal guinea pig brain stem. AB - Opioid receptor binding of morphine-6-beta-D-glucuronide (M6G), morphine and [3H][D-Ala2,N-methylPhe4-Glyol5]enkephalin (DAMGO) were determined in neonatal guinea pigs. Pontomedullary membranes specifically bound [3H]DAMGO, which was displaced by M6G and morphine. The KI for M6G and morphine were 15.1 nM and 5.0 nM, respectively, and did not change between day 3 and day 7 after birth. KD for [3H]DAMGO binding was constant (1.1nM), however Bmax increased from 62.2 to 88.3 fmol/mg protein between days 3 and 7 (P < 0.01). This 42% increase in mu receptors may play a role in the increased potency of M6G respiratory effects for guinea pigs during the first week after birth. PMID- 7781164 TI - Midkine is present in the early stage of cerebral infarct. AB - Expression of midkine (MK), a growth factor with neurotrophic activities, was examined immunohistochemically in experimental cerebral infarct of rats. From postoperative day 1 to day 7 after the onset of infarct, anti-MK immunoreactivity was observed in the surrounding ischemic zone of the infarct but not in the necrotic lesion. The immunoreactive material was identified to be MK by Western blotting. On day 14, anti-MK immunoreactivity became negative. Absence of MK in the normal brain was verified both by immunohistochemical staining and Western blotting. The induced expression of MK is an early event: increased expression of glial fibrillary acidic protein (GFAP), a marker of astrocytes, started on day 4 and continued to day 14. These findings suggest that MK is produced around the site of nerve damage and plays a role as a reparative neurotrophic factor during the early phase of cerebral infarct. PMID- 7781165 TI - Molecular characterization of EAP-300: a high molecular weight, embryonic polypeptide containing an amino acid repeat comprised of multiple leucine-zipper motifs. AB - In this study we report the biochemical and initial molecular characterization of EAP-300, a developmentally regulated embryonal protein that has been shown previously to be expressed by radial glia in various regions of the CNS, including putative glial barriers. In the present study we have shown that the 300 kDa EAP-300 polypeptide is developmentally regulated in all tissues expressing the protein, which include various PNS and CNS tissues and muscle. In neural tissue the protein is readily detected during early embryogenesis, subsequently down-regulated at later stages, and is not detected in the adult. In contrast to neural tissue, small amounts of the protein are expressed in heart, consistent with earlier studies which showed that EAP-300 expression was maintained in the Purkinje cells of the heart conduction system. Metabolic labeling demonstrates that EAP-300 is a phosphoprotein, and is fatty acylated based on incorporation of [3H]palmitate. We also show that the normal developmental down-regulation of EAP-300 by glia does not occur in vitro, and these data therefore suggest that the signal(s) that regulates EAP-300 gene expression during development in vivo is absent in dissociated cell cultures. We have also initiated molecular studies of EAP-300 by screening embryonic brain cDNA expression libraries with a mixture of EAP-300 monoclonal antibodies. Sequence analysis of partial EAP-300 cDNAs indicate that the protein is related, if not identical, to IFAPa-400, a developmentally regulated intermediate filament associated protein in chick that is proposed to participate in cell differentiation. These studies also indicate that EAP-300 mRNA is developmentally regulated and is expressed by glial cells in putative CNS barrier structures. Our studies also suggest that two pools of EAP-300 may exist in cells, implying that unlike IFAPa-400 the EAP-300 protein may not always be associated with intermediate filaments. Interestingly, our studies demonstrate that EAP-300 contains a novel repeat amino acid domain comprised of multiple leucine-zipper motifs, which may contribute to its function during glial differentiation. PMID- 7781166 TI - Cocaine inhibits central noradrenergic and dopaminergic activity during the critical developmental period in which catecholamines influence cell development. AB - Cocaine produces neurobehavioral damage in the fetus and neonate both through its ischemic actions and through direct effects mediated by the drug within the developing brain. The replication and differentiation of catecholaminergic target cells are controlled in part by neurotransmitter input and the current study assess whether cocaine modifies the function of these neurons during the critical periods in which target cell programming occurs. Neonatal rats (1, 7, 14 and 21 days old) were given cocaine (30 mg/kg) acutely and the turnover of norepinephrine and dopamine, a measure of synaptic activity, was evaluated in vivo in three different brain regions known to be adversely affected by cocaine. For norepinephrine, cocaine suppressed transmitter turnover in the immediate postnatal period in all regions, reaching a maximal effect within the first 2 postnatal weeks; at subsequent ages, the inhibitory actions were no longer evident. For dopamine, an inhibitory effect also appeared during the first postnatal week, but by 14 to 21 days the effect was replaced by the excitatory response that is characteristic of mature brain; effects on dopamine turnover were restricted to the forebrain. The inhibitory effects of cocaine on immature brain could not be attributed to localized actions at the nerve terminal itself (blockade of reuptake, autoreceptor activation, local anesthesia), but instead are likely to represent reductions in nerve impulse activity. Brain development in the neonatal rat corresponds to fetal stages in man, and thus the transient ability of cocaine to interfere with noradrenergic and dopaminergic activity during the period in which differentiation is being patterned by neurotransmitter input, may be important in the neurobehavioral teratology of cocaine. PMID- 7781167 TI - Alteration of PFK subunit protein, synthesis, and mRNA during neonatal brain development. AB - During neonatal maturation of rat brain, a similar biphasic relationship exists between the previously reported pattern of glucose utilization and levels of each type of 6-phosphofructo-1-kinase (PFK) subunit protein, relative synthesis, and mRNA. The increasing amounts of each subunit isoform generally correlated with elevated protein synthesis which was promoted by greater amounts of each type of subunit mRNA. For each parameter, the early phase, 1 to 10 days after birth, was characterized by small increases, and the subsequent period from ten to thirty days postpartum was characterized by a much greater rate of increase. By 30 days after birth, adult values were observed. The apparent efficiency of translation of each type of PFK subunit mRNA in brain suggests that the M-type subunit mRNA is the most efficient and that the L-type subunit mRNA is the least. The greatest relative increases in subunit protein, mRNA, and synthesis were observed for the C-type subunit. Since enhanced translation apparently makes little, if any, contribution, a possible explanation of these phenomena could be increased transcription of the PFK genes. These neonatal changes could involve age dependent alteration of methylation of the PFK gene promotor(s) and/or activity of effectors of the transcription of the PFK genes. PMID- 7781168 TI - Arg-vasopressin content in the suprachiasmatic nucleus of rat pups: circadian rhythm and its development. AB - To investigate the development of Arg-vasopressin (AVP) content and its diurnal rhythm in the suprachiasmatic nucleus (SCN), AVP was measured by enzyme immunoassay in the rat pup SCN punched out from tissue slices obtained at postnatal day (PD) 1, 5, 10, 12 and 20 from animals maintained under a light-dark cycle (LD). The AVP levels, measured at a restricted time of day, increased from PD1 reaching the adult level at PD10-12. Diurnal rhythm similar to that in adults was evident at PD10-12 under the LD conditions used. The peak value of AVP was observed at the earlier light period, and its trough occurred at the end of the light period. The circadian rhythm remained for 7 days under constant dark (DD) or constant light (LL) conditions. These results indicate that the AVP, one of the output signals from the SCN, starts to oscillate after PD10-12, and shows a free-running rhythm during the nursing period. PMID- 7781169 TI - Epileptogenesis in immature neocortical slices induced by 4-aminopyridine. AB - The laminar site of onset of 4-aminopyridine (4AP)-induced epileptiform discharges in immature neocortical brain slices was localized to layer V using conventional extracellular field electrodes, current source-density analysis (CSD), and subdivided slices. Intracellular patch-electrode recordings in immature layer V neurons confirmed that intrinsically bursting (IB) neurons were not present at the ages studied or with bath application of 50-200 microM 4AP. IB properties were not being masked in the younger animals by the patch electrodes because typical IB neurons in layer V were seen in older rats when the same intracellular techniques were used. These results demonstrate that epileptiform activity can be initiated in the absence of IB neurons, and suggest that other factors are responsible for the preferential onset in layer V. PMID- 7781170 TI - A study of double-labeled retinal ganglion cells from the superior colliculus in the developing albino rat. AB - We studied the distribution pattern and percentage of bilaterally projecting, double-labeled retinal ganglion cells in the albino rat by the retrograde fluorescent double labeling. Forty-five albino (Wistar, Japan Clea) rats of either sex and of different stage of development ranging in age from the day of birth (Day 0) to Day 30, were used. With the rats under deep anesthesia, we pressure injected 0.02 microliter of 15% Evans blue (EB) and 0.02 microliter of 4% Fluoro-gold (FG) into the right and left superior colliculi, respectively; for rats older than 5 days, the volume of each tracer was 0.04 microliter. The animals were perfused with formol-saline 48 to 72 h later and the brain and eyeballs were excised and sectioned. Double-labeled cells were found over almost the entire retina, with the concentration in the lower temporal crescent in rats up to day 1; concentration gradually shifted to the ventral half between days 5 and 10. After day 15, double-labeled cells were found only in the ventral temporal crescent of the retina, which is the pattern in the adult rats. The percentages of retinal ganglion cells that were double-labeled at days 0, 1, 5, 7, 10, 15, 20, 25 and 30 were 60.2, 51.6, 60.5, 57.6, 62.2, 60.7, 55.7, 45.2, and 39.1, respectively. After day 10, the percentage of such cells decreased steadily. PMID- 7781171 TI - Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat. AB - Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta family isolated from the rat glial tumor cell line, B49. In embryonic dopaminergic (DA) neurons in vitro, GDNF promotes survival, high-affinity dopamine uptake, and neurite outgrowth. We have used a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific to GDNF to study the developmental expression of GDNF mRNA in central nervous system (CNS) and peripheral organs of embryonic rat on gestational days E11.5, E13.5 and E18, neonatal rat on postnatal days P0 and P10, and adult rat. GDNF mRNA is expressed throughout the CNS, with highest levels in P0 spinal cord and in P0 and P10 striatum. Lower levels are present in the brainstem (including the ventral mesencephalon, which contains the DA neurons of the substantia nigra), cerebellum, diencephalon, and telencephalon, as well as in primary cultures of cerebellar granule cells prepared from P7 cerebellum and astrocytes prepared from P1 cortex. The cerebellum has an unusual temporal pattern of expression, high at birth and in the adult, but undetectable at P10. GDNF mRNA is also expressed in many peripheral tissues at higher levels than in brain. These include embryonic limb bud, kidney and gut; neonatal kidney, gut, lung and testis; and adult lung, liver and ovary. In addition to the predicted RT PCR product, we also observed a minor band which was shown to be identical to GDNF in the mature peptide sequence, but which has a 78 base pair deletion in the preproprotein sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781172 TI - Effect of transient neonatal muscle paralysis on the growth of soleus motoneurones in the rat. AB - The postnatal growth of soleus motoneurones was studied during normal development and following transient paralysis of the soleus muscle in neonatal rats. Paralysis was achieved by implanting a silicon strip containing alpha bungarotoxin alongside the soleus muscle in rat pups within 3-6 h of birth. The soleus muscle was completely paralysed for at least 24 h, and by 9 days neuromuscular transmission was fully restored. The soma size of normal and target deprived soleus motoneurones was compared at intervals during the first 3 postnatal weeks and in adults, using the retrograde horseradish peroxidase technique. There was a four-fold increase in the soma area of normal motoneurons during the first 3 postnatal weeks, with the greater part of the increase occurring between 7 and 14 days. At 3 days, the distribution of soma areas was unimodal and became bimodal by 21 days. Paralysis during the first postnatal week did not significantly affect the developmental changes in motoneurone soma area or their distribution up to 3 weeks of age. Thus, motoneurones deprived of functional neuromuscular contact appear to grow normally during the early postnatal period, although previous results show that at later stages (2-3 months of age), many of these motoneurones die and the remaining cells are smaller than normal. PMID- 7781173 TI - The effect of mercury vapour on cholinergic neurons in the fetal brain: studies on the expression of nerve growth factor and its low- and high-affinity receptors. AB - The effects of mercury vapour on the production of nerve growth factor during development have been examined. Pregnant rats were exposed to two different concentrations of mercury vapour during either embryonic days E6-E11 (early) or E13-E18 (late) in pregnancy, increasing the postnatal concentration of mercury in the brain from 1 ng/g tissue to 4 ng/g tissue (low-dose group) or 11 ng/g (high dose group). The effect of this exposure in offspring was determined by looking at the NGF concentration at postnatal days 21 and 60 and comparing these levels to age-matched controls from sham-treated mothers. Changes in the expression of mRNA encoding NGF, the low- and high-affinity receptors for NGF (p75 and p140 trk, respectively) and choline acetyltransferase (ChAT) were also determined. When rats were exposed to high levels of mercury vapour during early embryonic development there was a significant (62%) increase in hippocampal NGF levels at P21 accompanied by a 50% decrease of NGF in the basal forebrain. The expression of NGF mRNA was found to be unaltered in the dentate gyrus. The expression of p75 mRNA was significantly decreased to 39% of control levels in the diagonal band of Broca (DB) and to approximately 50% in the medial septal nucleus (MS) whereas no alterations in the level of trk mRNA expression were detectable in the basal forebrain. ChAT mRNA was slightly decreased in the DB and MS, significantly in the striatum. These findings suggest that low levels of prenatal mercury vapour exposure can alter the levels of the NGF and its receptors, indicating neuronal damage and disturbed trophic regulations during development. PMID- 7781174 TI - Induction of labor using prostaglandin E2 (PGE2) vaginal gel in triacetin base. An efficacy study comparing two dosage regimens. AB - OBJECTIVE: To compare two dosage regimens for the administration of vaginal prostaglandin gel in triacetin base for induction of labor. METHODS: Seventy subjects planned for elective induction of labor at term were randomized to treatment with PGE2 vaginal gel every 6 or 12 hours. The 6-hourly group received an initial dose of 1 mg, followed by 2 mg at 6 hour intervals for a maximum of two additional doses if not in active labor. The 12-hourly group had an initial dose of 2 mg followed by two additional doses at 12 hour intervals if not in active labor. RESULTS: Successful induction rate was higher in the 12-hourly as compared to 6-hourly gel regimen (100% vs. 91%, P > 0.05). Twelve hours after the initial dose, delivery occurred in 34% delivery had occurred in 57% and 37% respectively (P < 0.01). We found no difference in the induction-active labor interval (P > 0.05), and the induction-delivery interval (P > 0.05) between the two groups. Active labor followed a single dose of gel in 66% of the 12-hourly group compared to 40% of the 6-hourly group (P < 0.01). Syntocinon augmentation was needed in 6% of subjects in the 12-hourly group as compared to 26% in the 6 hourly group (P < 0.01). The cesarean section rate was similar in both groups. Uterine hyperstimulation occurred less frequently in the 12-hourly group (P < 0.05). The perinatal outcome was similar in both groups. CONCLUSIONS: The 12 hourly regimen was more effective than the 6-hourly regimen in initiating labor. The majority of the subjects in the 12 hourly group achieved labor following a single dose of gel. Induction delivery interval, however, was similar in both groups. PMID- 7781175 TI - Pregnancy in heart transplant recipients. Case report and review. PMID- 7781176 TI - Anatomo-clinical considerations on the ovarian fibroma. AB - The Authors analysed from an anatomo-clinical point of view, 17 cases of ovarian fibroma, observed during the period between 1968 and 1992. The incidence of ovarian fibroma in this study was 2.52% and it affected women in different age groups, though with greater frequency those above 50 years. Even the symptomatology was variable and was characterized by pain in the hypogastric quadrant (47.1%); alteration of the menstrual cycle (17.6%); metrorrhagic episodes (17.6%); sterility (5.9%). Due to the fact that the ovarian fibroma can appear at any age, this suggests different surgical approaches according to age, general conditions of the patient and fertility. PMID- 7781177 TI - The wording of the informed consent in gynecology. AB - In many western States medical activity is characterized by legal difficulties regarding the patients' consent. In this paper we have confronted the medical and legal problems connected to the wording of the informed consent in diagnostic and therapeutic practice in gynecology and obstetrics. In this area the role of Scientific Societies seems ever more important in that they could carry-out an important task by having the possibility of acquiring and coordinating the maximum amount of knowledge in both the specialistic medical field and the judiciary field. Here, we discuss the various aspects of the preparation of appropriate forms for correct patient information and the valid acquisition of the patient's consent for medical records. PMID- 7781179 TI - Menstrual patterns, pain symptoms, body mass index and smoking habits in women with endometriosis. AB - Epidemiologic studies have investigated the risk factors for endometriosis, but currently the results are still controversial. The aim of this study is to evaluate the incidence of some of the risk factors that have been involved with endometriosis to better understand the natural history and evolution of this disease. The medical records of 186 women with laparoscopic diagnosis of endometriosis were studied. We analysed the characteristics of the menstrual cycle, the presence of pain symptoms and the familiarity for endometriosis. Moreover, the body mass index of all patients and the average cigarettes smoked per day were calculated. Despite the fact that some of the data collected resulted to be statistically significant when compared among the four stages of endometriosis, the roles of the many factors that have been associated with the risk or the evolution of pelvic endometriosis still remain unknown. PMID- 7781178 TI - The management of persistent occipito-posterior position. AB - Persistent occipito-posterior position (POP) is found in about 1% of labors, and its management is still controversial. A study group of 319 patients with POP deliveries were screened and analyzed for prepartum, intrapartum and postpartum parameters. A control group of the same size was matched for maternal age (mean 27-28 +/- 5.22 yrs), gravidit (mean 2.52 +/- 1.95) and parity (mean 1.13 +/- 1.67). Statistically significant differences were found between the study and the control groups regarding the incidence of instrumental (forceps/vacuum) deliveries, prolonged second stage, pregnancy-induced hypertension, prostaglandin E2 induction, premature rupture of membranes and episiotomy. A discussion is presented evaluating the possible significance of these findings. Although the high rate of instrumental deliveries encourages active management of POP labors, the authors advocate a more conservative approach. PMID- 7781181 TI - Substitutive hormonal treatment in postmenopause. AB - The social impact of menopause is stressed by the actual life expectancy of women. One of the most important post-menopausal alterations--"osteoporosis"--is considered. Particular attention is focussed on therapeutical aspects. PMID- 7781180 TI - Transvaginal Doppler ultrasound with colour flow imaging in benign and malignant ovarian lesions. AB - Since early detection of ovarian cancer is difficult, most cases are diagnosed at advanced stages. The imaging diagnosis is based on pattern classification and is limited with respect to the precise determination of malignancy. High-frequency transvaginal sonography improves the ability to detect malignant ovarian tumors over that of transabdominal route, however, the predictive values are unsatisfactory because of inability to distinguish between malignant and benign tumors that have similar morphologic characteristics. The introduction of transvaginal colour flow imaging has allowed detection of low-resistance intratumoral blood vessels, characteristic of malignant tumors, and visually reflected the state of blood flow of an ovarian tumor. These two ultrasonographic methods were used for diagnosis of ovarian tumors in 65 women treated in our Department of Obstetrics and Gynecology. Waveforms of the parenchymal tumor arteries or tumor surface arteries were compared using value of the resistance index (RI). The sensitivity, specificity and accuracy of the preoperative RI in detecting malignant ovarian tumors were 100%, 94%, 95.4% respectively. The sensitivity, specificity and accuracy of preoperative suspicious sonographic findings in detecting malignant ovarian tumors were 100%, 61% and 71%. Positive and negative predictive values of colour flow imaging were 85% and 100%, whereas for grey-scale transvaginal ultrasonography they were 46% and 100% respectively. The findings of this study suggest that transvaginal colour Doppler is a method which is superior to the other methods for preoperative evaluation of ovarian malignancy. PMID- 7781182 TI - Pregnancy and myasthenia gravis. A case report. AB - Myasthenia gravis in pregnancy is seen very rarely. We present such a case who was diagnosed and treated in our department. PMID- 7781183 TI - Histochemical aspects of nucleoproteidic metabolism of human embryos. A histofluoroscopic study. AB - The Author, after stressing the importance of proteic syntheses in the vital processes of each cell and the role played by nucleic acids in such metabolic processes, underlines the importance of histochemical studies on nucleoproteidic metabolic in the embryo, and briefly illustrates the most important features of the fluorescent method. The Author further relates the results of his personal research conducted by means of microfluoroscopy after acridine orange chromization on histological sections of human embryos. The results are documented by the enclosed photographs, and their significance is briefly discussed. PMID- 7781184 TI - Pregnancy in adolescents. A case-control study. AB - OBJECTIVE: to investigate pregnancy outcome and incidence of pregnancy-related disorders in the adolescent. DESIGN: a matched control retrospective study. SUBJECTS: pregnant adolescents aged 14 to 19 years admitted to the Departments of Obstetrics and Gynecology--Policlinico Umberto I, between the years 1984 and 1993; a comparable number of pregnancies aged 20 to 24 years was considered as a control group. RESULTS: In the 10 yrs. period a total of 304 pregnancies in adolescents were considered. Preterm deliveries were 9.5% in the adolescent group vs 5.9% in control (P > 0.05). A higher incidence was found in number of cesarean section (P < 0.001), spontaneous abortion (P = 0.003), intrauterine growth retardation (P = 0.04) and fetal distress (P = 0.04) in the adolescent group vs matched controls. Also mean birth weight was significantly lower in the adolescent group when compared with normal group (P < 0.001). CONCLUSION: we found a higher incidence of obstetric complications, such as IUGR, acute fetal distress in labor and lower birth weight, in the adolescent group, resulting in a higher number of cesarean sections. We hypothesise that the relative state of "hypoarterialisation" characteristic of the adolescent uterus may be involved in the afore-mentioned complications. PMID- 7781185 TI - High risk pregnancy in a patient with angioma of the corpus callosum. AB - Literature data indicate that rupture of arterovenous malformations is 4 times more frequent in pregnant women. The Authors present a case of cerebral hemangioma of the third medium anterior of the corpus callosum diagnosed in a patient at the 28th gestational week by Magnetic Resonance scan. The patient underwent elective caesarean section under peripheral anesthesia (peridural and spinal block by Bupivacaine) and delivered a male infant 4560 gr, 52 cm. The postoperative course was uneventful. The arterovenous malformation constituted an important anesthesiologic risk factor but the Authors conclude that caesarean section can be safely performed with a very careful anesthesiological time schedule and a reliable haemodynamic monitoring. PMID- 7781187 TI - Re: Board certified in QEEG??? PMID- 7781186 TI - Leiomyoma of the female urethra. A case report and review. AB - A case of urethral leiomyoma in a 39 year old woman is reported. It is always a benign neoplasia, frequently hormone-dependent, rarely relapsing after excision. An accurate review of the literature has found over 110 cases up to date, in opposition to a recent publication in the Journal of Urology in 1992, which reported only 36 cases up to that year. PMID- 7781188 TI - Topographic analysis of EEG photic driving in normal and schizophrenic subjects. AB - In a 19-channel EEG photic driving paradigm the steady-state evoked response was studied in schizophrenic patients and normal controls. Seventeen drug-free patients and 15 normal controls were compared. Schizophrenic patients had lower EEG photic driving in the alpha range, particularly in the high alpha frequency band (p = 0.08). Topographic analysis revealed that the group differences were primarily located in the mid-frontal, central and parietal areas (p < 0.05). Temporal and lateral frontal lobe alpha remained the same in the two groups. Separate analysis of eye movement (EM) showed an opposite effect on the alpha frequency photic driving as compared to that on the resting alpha EEG. EM decreased the resting alpha EEG and increased the photic driving. This finding suggested that the lower EEG photic driving in the schizophrenic patients could not be explained by the eye movement artifact. We hypothesize that the 10 Hz range photic driving that reflects the intrinsic EEG spindle generation in the thalamus may play an important role in the psychophysiology of schizophrenia. PMID- 7781189 TI - Sleep onset: scoring criteria in patients with sleep apnea syndrome. AB - It has been suggested that in patients with sleep apnea syndrome (SAS) modified scoring criteria may improve accuracy in the determination of sleep onset in the Multiple Sleep Latency Test (MSLT). Scoring in 30-sec epochs according to the standard criteria requires more than 50% of the epoch asleep to score sleep latency (SL). In patients with SAS, short apneas with arousals could prevent the accurate determination of SL. This study compared three time-duration epochs (5 sec, 10-sec, 30-sec) for scoring SL in patients with SAS. Sleep onset during a single sleep latency test, the morning subsequent to a nocturnal polysomnogram, was determined by the criterion of at least 50% of the epoch asleep. Neuropsychological evaluation was performed immediately after the single sleep latency test. There was no statistically significant difference in time to fall asleep as defined by 10-sec and 30-sec epochs, but SL defined by 5-sec epochs was significantly shorter than SL defined by 10-sec and 30-sec epochs. Wilkinson Addition Test correct score correlated better with SL as defined by 30-sec epochs. The results imply that the level of sleepiness measured by 30-sec epochs may be more useful to appreciate behavior and performance. PMID- 7781190 TI - Effects of antiepileptic drugs on EEG background activity in children with epilepsy: initial phase of therapy. AB - The effects of antiepileptic drugs (AED) on EEG background activity were evaluated in 37 newly treated children with epilepsy, compared with 46 age matched healthy controls. Before AED therapy, the children with epilepsy, both partial (treated with carbamazepine, CBZ group) and generalized seizures (treated with valproic acid, VPA group), already exhibited significant slowing of EEG with increased delta and decreased alpha power. Following 3 to 6 months of AED therapy, this EEG slowing was enhanced in the CBZ group and reduced in the VPA group. Following 1 year of AED therapy, an increase in frequency was recognized in the CBZ group. These results suggest that 1) most children with epilepsy already exhibit slowing of the EEG at the onset of seizures, which may reflect CNS developmental deficit, 2) the short-term effects on EEG are different between CBZ and VPA, and 3) EEG development with age continues under continuous AED administration. The EEG background activity in children with epilepsy is affected by many factors, which include the underlying CNS dysfunction of the epilepsy itself and also AED therapy (type of AEDs, duration of therapy, etc). PMID- 7781191 TI - Effects of zonisamide on BAEP, SSEP and P300. AB - The effects of zonisamide on BAEP, SSEP and P300 were studied. The subjects were 12 patients (4 men and 8 women) with untreated epilepsy. Their ages ranged from 16 to 59 years, with a mean of 26.3 +/- 12.0 years. The daily dose of zonisamide was between 200 mg. to 600 mg. (2 to 6 tablets, 2.9 +/- 1.1 tablets on average). The serum concentrations of zonisamide ranged from 11.4 to 32.5 micrograms/ml, with a mean of 18.7 +/- 8.5 micrograms/ml 1 year after administration. Central conduction time and latency in BAEP and SSEP and amplitude, response time and latency in P300 were investigated. There were no significant differences in any of the tests. Zonisamide did not affect any of these evoked responses and may be less toxic to the central nervous system than other antiepileptic drugs. PMID- 7781192 TI - Late onset absence seizures in multiple sclerosis: a case report. AB - A 38-year-old woman was admitted to hospital because of generalized tonic-clonic attacks and late onset absence seizures. EEG and Video-EEG showed 3-4 hz generalized spike and wave discharges lasting 1-8 seconds, which were associated with impairment of consciousness and unresponsiveness. MR scan revealed multiple demyelinating lesions, including the most prominent one in the mesial frontal region that we suppose might be responsible for electroclinical absence seizures. After investigation the diagnosis of multiple sclerosis was made. Possible pathophysiological mechanisms and differential diagnosis of tonic-clonic and absence seizures in MS are discussed. PMID- 7781193 TI - Study of the alpha frequency band of healthy adults in quantitative EEG. AB - The qEEG of the alpha band in 115 healthy adults, and for comparison the SPM of 244 patients, were studied. The alpha band was divided into three subgroups: alpha 1 (8-8.9Hz), alpha 2 (9-10.9Hz) and alpha 3 (11-12.9Hz). This method could both demonstrate the dominant rhythm of healthy adults and discover alpha slowing. The distribution of the level of power and percentage of frequency in alpha 1, 2 and 3 varied on different head regions. While the distribution of alpha 1 was the same as the theta and delta bands, there was a trend toward abnormally high power of alpha 1 and theta bands in patients. PMID- 7781194 TI - Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic outcome. AB - To determine if quantitative electrophysiologic measures correlate with pharmacotherapeutic response, we conducted a retrospective analysis of treatment outcomes in sequential patients with attention deficit disorder and affective disorders. One hundred medication-free patients meeting DSM-III-R criteria for attentional and affective disorders underwent pretreatment EEG, quantitative Neurometric EEG, and physical/laboratory examinations. Attention-disordered patients were first treated with a stimulant, secondarily with an antidepressant, and tertially with an anticonvulsant. Affectively disordered patients were treated initially with antidepressant, and secondarily augmented with anticonvulsant or lithium. Tertiary treatment was a stimulant. Patients were assessed up to 6 months. A Clinical Global Improvement score was assigned. Similar Neurometric subgroups were identified within both the attentional and the affectively disordered patients. Subgroups were relative alpha frequency excess, relative theta frequency excess, and/or inter-hemispheric hypercoherence. Without regard to DSM-III-R diagnosis, there were robust correlations between Neurometric subgroup membership, responsivity to selected pharmacologic agent class(es), and clinical outcome. The frontal alpha excess subgroup was 87% responsive to antidepressants. The frontal theta excess subgroup was 100% responsive to stimulants. The frontal alpha excess/hypercoherent subgroup was 85% or more responsive to anticonvulsants/lithium. The frontal theta excess/hypercoherent subgroup was 80% responsive to anticonvulsants. Patients with similar Neurometric features responded to the same class(es) of psychopharmacologic agent(s) despite their DSM-III-R classification. PMID- 7781195 TI - QEEG in hemophiliacs with HIV infection. AB - Conventional visual analysis of the EEG was performed on 320 hemophiliacs infected with HIV, who spanned the range of the Walter Reed (WR) system for classifying clinical stage of HIV infection, and on 50 HIV seronegative hemophiliac controls. Intermittent or paroxysmal slowing was the conventional EEG abnormality most commonly seen in early stages of HIV infection (stages WR1 and 2), with increased focal epileptiform activity and generalized slowing appearing in patients with the full clinical syndrome of AIDS (WR6). Slowing of the manually measured alpha rhythm was noted in stages WR2 and above. Quantitative EEG (qEEG) was obtained in a subset of 103 male HIV seropositive male hemophiliacs and 35 male HIV seronegative hemophiliac controls. The principal findings were a progressive relative increase in theta power with a tendency towards an anterior topographic distribution, and a progressive decline of spectral power in fast alpha relative to slow alpha with increasing severity of HIV disease. Significant qEEG differences from controls were apparent in WR2 subjects (seropositive with lymphadenopathy and without other constitutional symptoms), and were relatively greater in WR3-6 subjects. These results suggest sensitivity of qEEG to early CNS involvement with HIV infection. PMID- 7781196 TI - The EEG in psychiatry: an outline with summarized points and references. PMID- 7781197 TI - Selected papers presented at the Nephropharmacology 3 meeting. Ulm, 1994. PMID- 7781198 TI - Endothelin (ET-1) is involved in the contrast media induced nephrotoxicity in children with congenital heart disease. AB - In 77 children with congenital heart disease urinary endothelin-1 (ET-1), an indicator of intrarenal endothelin release, was compared to urinary excretion of total protein, albumin, immunoglobuline G (IgG), alpha 1-microglobuline (alpha 1 MG), N-acetyl-beta-D-glucosaminidase (NAG) and villin. Urine samples were collected the day before and immediately after cardiac angiography with high (Conray 70; n = 56; CON) or low osmolality contrast media (Solutrast 300; n = 21; SOL) to assess the relationship between urinary endothelin and glomerular and tubular nephrotoxicity of contrast media. The children were further subdivided according to age: less than 1 year-CON 1 (n = 20); SOL 1 (n = 12) and 1-18 years CON 2 (n = 36); SOL 2 (n = 9). Results (median): 1. There are no significant changes in total protein-, albumin- and IgG-excretion as parameters of glomerular toxicity. 2. Tubular toxicity of contrast media is shown by significant increase of alpha 1-MG-(10.0 to 23.2 mg/g Crea; p < 0.001), NAG-(5.9 to 9.6 mg/g Crea; p < 0.001) and Villin-excretion (1.0 to 2.0 STS, p < 0.001) in all children. 3. Endothelin excretion (101.0 to 163.0 ng/g Crea, p < 0.001) and concentration (42.5 to 56.0 pg/ml; p < 0.001) were elevated after angiography in all children. 4. The changes in endothelin excretion are correlated to the changes in alpha 1 MG (r = 0.65; p < 0.001) and NAG (r = 0.43, p < 0.001) in all children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781199 TI - Methylprednisolone pharmacokinetics and pharmacodynamics in chronic renal failure. AB - Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion and cell trafficking were compared in 6 chronic renal failure (CRF) subjects and 6 healthy controls. After IV administration of MP 0.6 mg/kg as Solu-Medrol, the pharmacokinetics of methylprednisolone were similar. The clearance was about 280 ml/hr/kg, volume of distribution was 1.1 l/kg, t1/2 was 2.7 hr, and fraction unbound was 0.2. Physiologic pharmacodynamics models were applied for the suppression of cortisol secretion and recirculation of basophils, T-helper cells, and T-suppressor cells. The net response (area under the curve) and inhibitory concentrations (IC50) of methylprednisolone for each pharmacodynamic parameter were similar in both groups. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic/dynamic changes of methylprednisolone may offer a therapeutic advantage for CRF patients. PMID- 7781200 TI - Single dose kinetics of piperacillin during continuous arteriovenous hemodialysis in intensive care patients. AB - Piperacillin (Pi) kinetics in patients with acute renal failure treated by continuous arteriovenous hemodialysis (CAVHD) are not known. Therefore, dosing regimens have been based on kinetic data derived from patients with chronic renal failure and principal pharmacokinetic considerations [Reetze-Bonorden et al. 1993]. From these estimations it has been predicted that approximately 30% of the dose of Pi is removed by CAVHD (dialysate/ultrafiltrate (D/UF) flow rate 1.5 liter/hour). To confirm this estimate single dose (4g i.v.) Pi kinetics were studied in 12 intensive care patients with anuric acute renal failure due to septicemia treated by CAVHD. Pi plasma and D/UF levels were measured by HPLC. Sieving/Saturation of Pi in the D/UF was 0.71 +/- 0.21 (+/- SD). With a mean D/UF flow rate of 20.4 +/- 1.5 ml/min, the mean extracorporal clearance (Clextra) was 12.2 +/- 1.0 ml/min and accounted for 29% (range 14-48%) of total body clearance (ClB = 47.1 +/- 22.3 ml/min). In 7 out of 12 patients the fraction of the dose eliminated by CAVHD reached a significant value above 25%. The mean volume of distribution (Vd) and elimination half life (t1/2) were 25.8 +/- 3.8 liter and 7.4 +/- 2.9 hours, respectively. In conclusion the extent of extracorporal elimination of Pi by CAVHD was well in agreement with the estimation previously published. In intensive care patients with acute renal failure on continuous hemodialysis Pi dosing should take into account the possibly significant elimination of Pi. The usual dose for anuric patients may be increased by 50% to avoid underdosing in these critically ill patients. PMID- 7781201 TI - Saturable first-pass kinetics, plasma protein binding, and the furosemide intricacies. AB - An equation for saturable nonlinear first-pass kinetics is presented to discuss some contra-intuitive findings encountered with furosemide bioavailability. The diverging effects on steady-state bioavailability (Fss) are simulated for changes in maximal metabolic capacity (Vm), volume of distribution (Vd), Michaelis constant (Km), steady-state plasma concentration (Css), repetitively administered drug dose (Dss), dosage interval (Tau), liver plasma flow (Ql), absorption rate constant (Ka), and free plasma fraction (fp), where (Cssf = fp Css = const.) and (Kmf = fp Km = const.). [Formula: see text] The present concept is in line with observations indicating that furosemide bioavailability decreases from 60 to 45% in nephrotic syndrome patients whose plasma protein binding is reduced and hepatic clearance increased. These observations and our equation-based simulations show that furosemide must have a first-pass effect. Hepatic extraction of furosemide is not facilitated by albumin, and saturable first-pass kinetics can not be used to explain an albumin paradox. PMID- 7781202 TI - Clinical experience transferring kidney transplant patients from Sandimmun to Sandimmun Neoral--results after 3 months. AB - The new galenic formulation of cyclosporine prepared as microemulsion (Sandimmun Neoral, SN) shows a significantly improved correlation between both trough level (Cmin) and dose. Moreover, since the bioavailability is increased by 20 to 30% on average, it may lead to a drug overexposure in so far malabsorbing patients. In order to assess safety and to establish an appropriate procedure to switch patients safely from conventional Sandimmun to SN, we initialized an open, stratified (transplant age) clinical trial enrolling 302 patients of our outpatient clinic. We used a simple 1:1 conversion of the patient's total daily dose. Trough drug levels, as well as serum creatinine, liver enzymes, uric acid, and blood pressure values were measured at baseline, at days 4, 8, 15, 29, and at month 3 after drug substitution. Within the three month observation period, the cyclosporine dose was reduced by 14.2% (204 +/- 60 mg/day baseline vs. 175 +/- 54 mg/day after conversion, p < 0.05). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs. 120 ng/ml, p < 0.05). This increase was accompanied by a slight increase in mean serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in mean uric acid values (p < 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < 0.05). Parallel to dosage reduction, drug trough levels had decreased after 1 month to baseline (112 ng/ml) and remained there for the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781203 TI - Therapeutic use of theophylline to antagonize renal effects of adenosine. AB - Experiments in laboratory animals clearly show that adenosine acts as a vasoconstrictive metabolite in the kidney. Adenosine receptor antagonists like theophylline can inhibit renal vasoconstriction in response to exogenous and endogenous adenosine. Based on these findings a number of experiments have been performed to test whether the vasoconstrictive action of adenosine in the kidney might be important also in pathophysiological states. In various animal models theophylline and other methylxanthine derivatives have been successfully employed to improve renal function after induction of acute renal failure. Clinical implications of these experimental findings comprise the prevention of acute renal failure following the administration of radio contrast media by theophylline. Another therapeutic aspect derives from experimental and clinical data showing that theophylline controls erythropoietin production in erythrocytosis after renal transplantation. PMID- 7781204 TI - Determinants of furosemide delivery to its site of action. AB - We have investigated the pharmacokinetic determinants of delivery of furosemide to its site of action in the renal tubules in patients and healthy volunteers. The bioavailability of furosemide is low and variable. Patients with renal disease may also have a low renal extraction of furosemide. In clinically relevant concentrations the free fraction of furosemide is inversely proportional to the plasma albumin concentration. A change in the free fraction of furosemide will change Clr, Clnr, and Vd in the same direction and that will cause minimal changes in the excretion rate of furosemide and its t1/2. A change in RBF will change the secretory clearance of furosemide to the same proportion and consequently also the excretion rate and its t1/2. PMID- 7781205 TI - Does L-arginine alter proteinuria and renal hemodynamics in patients with chronic glomerulonephritis and hypertension? AB - Endogenous nitric oxide (EDRF) plays an important role in the regulation of systemic and renal blood pressure by an alteration of vascular tone. To assess the effect of L-arginine (160 mumol/min i.v. for 3 hours), the precursor of EDRF, on blood pressure, protein-excretion and renal function (GFR = glomerular filtration rate, RPF = renal plasma flow) we performed a prospective, double blind, placebo controlled study. 18 patients with chronic glomerulonephritis (51.3 +/- 11.5 years), renal insufficiency (GFR < 65 ml/min) and hypertension were investigated for changes in GFR and RPF by continuous inulin- and PAH clearances and for changes in permselectivity by determination of protein excretion. L-arginine infusion results in a reduction of proteinuria (p < 0.05, t test). There is no significant effect on renal hemodynamics and mean arterial pressure (MAP). Comparing the excretion of the endogenous proteins, only albuminuria is decreased significantly (p < 0.01), whereas IgG-excretion is reduced slightly (p < 0.05). This can be considered as an indicator of a special influence on the mesangial cells or the basement membrane of the glomerulum itself by EDRF. In conclusion L-arginine reduces protein-excretion without significant alterations in renal hemodynamics and so might prevent a decline in renal failure. PMID- 7781206 TI - Renal hemodynamics in essential hypertensives treated with losartan. AB - ACE-inhibitors are known to have special renal effects, i.e. they increase ERPF, decrease the filtration fraction and lower proteinuria. These effects can be due to a decrease in angiotensin II (AII) levels as well as an increase in bradykinin. New and more specific AII-receptor antagonists may help to distinguish between effects exerted by angiotensin II and those exerted by bradykinin. We investigated the effects of losartan in 9 patients with essential hypertension (sitting mean diastolic blood pressure 95-120 mmHg). Renal hemodynamics were measured by continuous inulin-and PAH-clearance (GFR and RPF) after stopping antihypertensive therapy for 1 week, followed by a 2-week placebo period and after a 4-week treatment phase with losartan (50 mg/die) followed by a therapy with an ACE-inhibitor (ramipril 5mg/die). Additionally, urine albumin excretion (UAE) was measured. Treatment of patients with essential hypertension with losartan resulted in a significant decrease of MAP after three weeks of treatment (121 +/- 8 mmHg under placebo and 114 +/- 10 mmHg under losartan; * = p < 0.05). MAP after four weeks of losartan treatment was 115 +/- 11 mmHg. Regarding changes in renal hemodynamics we could not demonstrate a significant change for neither losartan nor the ACE-inhibitor. Urine albumin excretion was reduced by both treatment regimens in correlation to the magnitude of blood pressure reduction. Our data indicate that losartan induced a significant reduction in MAP in patients with essential arterial hypertension with only moderate effects on renal hemodynamics. PMID- 7781207 TI - [Multiorgan abnormalities in myotonic dystrophy--correlation among endocrine disorders, central nervous system involvements and gene analysis]. AB - Myotonic dystrophy (DM) is a disease involving multiple organs. To elucidate the extent of severity of the affected organs in a given individual, we performed an investigation of the Ellsworth-Howard test (EH test), intelligence quotient (IQ), apnea index (AI), and expanded DNA fragment (EF) size in 10 patients with DM. The EF size analyzed by standard Southern blot procedures using EcoRI digested genomic DNA extracted from the peripheral white blood cells and probed with cDNA25. In the EH test, these patients were divided into two groups according to the results of their phosphaturic responses (delta P). Of these, 5 patients (Group I) showed a positive delta P, while remaining 5 patients (Group II) showed a negative one. In both Groups I and II, their urinary cyclic AMP responses were positive. Group II showed a significantly low value in IQ (p < 0.02) and a significantly high value in AI (p < 0.02) as compared with Group I. EF size in Group II was found significantly larger than in Group I (p < 0.01). A positive correlation between delta P and IQ (p < 0.1), a significant negative one between delta P and AI (p < 0.01), and a negative correlation between EF size and delta P (p < 0.2) were observed. IQ was negatively (p < 0.05), and AI was positively (p < 0.05) correlated with EF size, which were statistically significant. Our results suggest that the extent of disease severity of the central nervous system is almost the same as that of endocrine organs, and that EF size is correlated with disease severities in both affected organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781208 TI - [Mirror movement due to the medial frontal lobe lesion]. AB - We reported a case with acquired mirror movement in upper limbs due to the lesion of right medial frontal lobe including supplementary motor area, and also discussed a possible mechanism underlying it. A 59-year-old right-handed woman developed left hemiparesis caused by cerebral hemorrhage in the right frontoparietal lobe, on April 5, 1981. She had right hemiparesis and right hemianopsia due to cerebral hemorrhage in the left parieto-occipital lobe, 13 days later. As the patient was recovering from paresis, mirror movement appeared on upper limbs. The features of the mirror movement of this case are summarized as follows: (1) it appeared when using both proximal and distal region of upper limbs; (2) it appeared on left upper limb when the patient intended to move right upper limb or on right upper limb when intended to move left upper limb, while it appeared predominantly in the former; and (3) it was more remarkably found in habitual movement using gesture and pantomimic movement for the use of objects, and it was found in lower degree when actual object was used or when the patient tried to imitate the gesture of the examiner. The lesions in MRI were found in medial region of right frontal lobe (supplementary motor area, medial region of motor area, and cingulate gyrus), right medial parietal lobe, posterior region of right occipital lobe, and medial regions of left parietal and occipital lobes. There was no apparent abnormality in corpus callosum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781209 TI - [Rest-activity and body-temperature rhythm disorders in elderly patients with dementia--senile dementia of Alzheimer's type and multi-infarct dementia]. AB - We simultaneously monitored rest-activity and body temperature (BT) rhythm in demented patients with sleep and behavior disorders using ambulatory wrist-worn actigraph and long-term monitoring system for 5-7 consecutive days. Subjects consisted of 19 patients with senile dementia of Alzheimer's type (SDAT) (M/F = 7/12, mean age = 71.7 years), 16 patients with multi-infarct dementia (MID) (M/F = 9/7, mean age = 75.2 years) and 9 normal controls (M/F = 4/5, mean age = 70.4 years). Both dementia groups showed a significant increase in percentage of nighttime activity. In the SDAT group, a significant positive correlation between the degree of dementia and total activity was observed, but not observed in the MID group. A significant high amplitude of BT rhythm was observed in the SDAT group comparing that in the MID or the control group. These findings indicate that the SDAT patients had a disrupted rest-activity rhythm with the severity of intellectual deterioration and increased night activity, while the circadian BT rhythm was remarkably well preserved, i.e. there was a dissociation between rest activity and BT rhythms in the SDAT group. On the other hand, the disruption of the rest-activity and BT rhythm in the MID patients was characterized by a concomitant decrease of amplitude, which seems to have no relation with the severity of dementia. Different mechanisms could be involved in characteristic disruption of the circadian rhythms in the 2 dementia groups. PMID- 7781210 TI - [Clinical and biochemical analysis of 27 patients with myoglobinuria of unknown causes]. AB - We examined the clinical and biochemical features of 27 cases with acute myoglobinuria who had been suspected of having metabolic myopathies. The systematic biochemical studies included the measurements of 13 glycolytic enzymes, mitochondrial respiratory chain enzymes, carnitine palmitoyltransferase (CPT) and 5 enzymes of fatty acid beta-oxidation. Enzyme defects were found in 9 patients using muscle biopsy specimens: phosphorylase deficiency in 3, CPT deficiency in 4 and phosphoglycerate kinase deficiency in 2. One patient was diagnosed as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with the histopathological examination and clinical data. A suspicion of beta-oxidation disorder was entertained in some patients of which the activities were about 50% of control means. However, no evidence to substantiate its significance as the enzyme defects was obtained from our data. Sixteen of 17 undiagnosed cases could be divided into two groups according to precipitating factors as follows: one had exercise as the factors and the other had infection. These groups also showed some differences in clinical features. In the infection group, myoglobinuria tended to progress more rapidly and was occasionally followed by acute renal failure. And some cases had additional associated conditions such as mental retardation or epilepsy. On the other hand, the exercise group had only myopathic symptoms. The difference in these clinical features between the two groups suggested that they had the different pathogenic mechanisms respectively. PMID- 7781211 TI - [Paroxysmal dystonic choreoathetosis with chronic hemolytic anemia and morphologically abnormal erythrocytes]. AB - A 38-year-old man was admitted to our hospital because of paroxysmal involuntary movement. He had a normal birth and normal development. No other members of his family had similar symptoms. He had attacks of choreoathetoic involuntary movement without loss of consciousness since about 11 years of age. Paroxysmal choreic movement occurred once or twice a month and lasted for 30 minutes to 4 hours. The attacks were intractable with phenytoin, phenobarbital, valproic acid, etc. He had slight disturbance of visual acuity due to toxoplasmosis and low intelligence (IQ 59, WAIS-R test). There were no other abnormal findings on general and neurological examinations. He was diagnosed as paroxysmal dystonic choreoathetosis (PDC) because of the typical attacks of paroxysmal choreic movement. He had macrocytic anemia with elliptocytes (13%) and stomatocytes (12%) but no acanthocytosis. There were increased reticulocytosis and low level of haptoglobin. Bone marrow aspiration showed increased erythroblasts. However, other hemolytic findings including bilirubin levels, Coombs test, osmolality tolerance test were normal. Biochemical analyses of erythrocyte membrane proteins and lipids, glycolytic enzymes activities and intermetabolites contents showed no abnormality. EEG revealed slow waves without abnormal paroxysmal discharges, and CT revealed no abnormal calcification. T2 weighted MRI showed bilateral multiple high intensity spots in the subcortical area, but no atrophy of the caudate nucleus. The pathogenesis of PDC is still unknown. In the present case, we suspect that a biochemical defect which had not been disclosed might result in abnormal erythrocyte membrane and PDC. PMID- 7781212 TI - [A case of secondary carnitine deficiency due to anorexia nervosa and severe liver damage]. AB - We reported an 18-year-old woman with anorexia nervosa and liver damage who showed carnitine deficiency. Her unbalanced diet had little carnitine, and severely damaged liver could not synthesize carnitine. Since total parenteral nutrition (TPN) and tube-feed formulas contain little or no carnitine, the patient had progressive weakness and muscle atrophy. Muscle biopsy revealed variability of fiber diameter, type 1 fiber atrophy and copious amount of lipid granules. Carnitine deficiency must be diagnosed in the early stage by muscle biopsy or muscle carnitine levels, and treated with oral intake of L-carnitine. PMID- 7781213 TI - [A case of localized hypertrophic neuropathy in the sciatic nerve]. AB - A 26-year-old male patient gradually developed muscular atrophy of the right lower leg over a two-year period. Neurological examination revealed absent Achilles tendon reflex and muscular atrophy of the right lower leg and right hamstring muscles. Conduction velocity of the F waves was delayed in the right posterior tibial nerve. A computerized tomography scan and magnetic resonance imaging revealed a mass lesion along the proximal segment of the right sciatic nerve. Exploration revealed a fusiformly swollen sciatic nerve. Histological examination showed that a swollen segment of the sciatic nerve was filled with onion-bulb formations of perineurial cells, consistent with the diagnosis of localized hypertrophic neuropathy. This condition should be added to several etiologies of monomelic amyotrophy. Electrophysiological studies and neuroimaging techniques were useful in obtaining differential diagnosis. PMID- 7781214 TI - [A case of acute sensory neuropathy]. AB - We report a 50-year-old man who developed sensory neuropathy of acute onset. It affected position and vibration senses very severely, and superficial sensations mildly. There were athetoid movements of the outstretched left arm when the eyes were closed. The upper limbs were more severely affected than the lower limbs. There was no weakness or atrophy in the limb muscles. Nerve conduction study and somato-sensory evoked potential showed normal function of motor nerves and axonopathy of the sensory nerves. Sural nerve biopsy disclosed fibrosis and marked loss of myelinated fibers, especially of large ones, and many fibers with myelin balls in teased preparations, indicating severe axonopathy. Electronmicroscopy confirmed severe degeneration and loss of myelinated axons with abundant myelin figures in schwann cells. There were no malignancy or other diseases that could cause sensory neuropathy, and he was diagnosed as having acute sensory neuropathy (ASN) of Windebank et al. ASN, a distinct syndrome characterized by axonal type neuropathy, should be segregated from acute and chronic inflammatory demyelinaiting neuropathies although the clinical features and CSF findings look alike. PMID- 7781215 TI - [Sequential neuroimaging in a patient with delayed post-hypoxic leukoencephalopathy]. AB - We described a patient with delayed cerebral demyelination following a post operatively hypoxic encephalopathy. A 65-year-old man, with a history of exposure to the atomic bomb at Hiroshima in 1945, suffered from hypoxia, hypotension and respiratory acidosis and became unresponsive 10 hours after a laminectomy for lumbar disc herniation, in December 1993. Following an emergent resuscitation, the patient had gradually recovered and could walk 2 weeks later. Three weeks after the insult, however, the patient developed an apallic state with frontal lobe signs. Except an increased level of myelin basic protein in the CSF, there were no other abnormal laboratory findings. Brain CTs showed a leukoaraiosis. MRI one month post-operation, demonstrated extensive high signal intensity areas in the cerebral white matter on T2-weighted image, and a gadolinium-enhanced spotty lesion in the right globus pallidus on T1-weighted image. Three months after the operation, the high signal intensity on T2-weighted image became more intensive and extensive, while the enhanced spotty lesion in the globus pallidus disappeared. The corpus callosum and cerebellar white matter were spared throughout the observation. The SPECT using 123I-IMP showed a hypoperfusion in the frontal lobe at 1 month. Three months later, the hypoperfusion areas extended to the whole cerebral and cerebellar cortices, relatively less affected in the motor area and basal ganglia. The patient had improved slightly over the next few months. We speculate that subclinical vulnerability in the white matter secondary to exposure to the atomic bomb, in addition to the incomplete prolonged hypoxia, hypotension and acidosis, caused selective cerebral demyelination in this patient. PMID- 7781216 TI - [Acute leukoencephalopathy in Filipino women--report of two cases]. AB - Two cases of acute leukoencephalopathy are reported. Both patients were Filipino women who had lived together in Japan for one month at the time of the onset. The first patient, 26 years old, suddenly developed right hemiplegia without fever. Small, high signal intensity lesions of the cerebral white matter were disseminated on T2-weighted magnetic resonance images. One week later, the patient became delirious, developed seizures, and lapsed into a comatose state with spastic quadriplegia. Corticosteroid was administered, resulting in improvement of consciousness levels. The patient was transferred to our hospital. Neurological examination disclosed severe pseudobulbar palsy and spastic quadriplegia without meningeal signs. Results of a cerebrospinal fluid examination were unremarkable. With magnetic resonance imaging, large irregularly shaped lesions were seen in both centrum semiovale as high signal intensity areas on T2-weighted images and low signal intensity areas on T1-weighted images. Concentric structures in the lesions were particularly observed on T1-weighted images. One year later, the patient improved from a bedridden state to a wheel chair bound state. The second patient, 23 years old, also developed right hemiplegia one week after the onset of the first case. MR imaging revealed small disseminated lesions in the cerebral white matter similar to those disclosed in the first case. From the onset, the patient was given corticosteroid, and experienced good recovery within one month. The clinical features, results of the laboratory examination, and MRI findings particularly in the first case suggest the diagnosis of so-called Balo's concentric sclerosis, despite the absence of pathological confirmation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781217 TI - [MR imaging of the anterior spinal artery in a case of bilateral vertebral arterial occlusion]. AB - A 66-year-old woman, who had been suffering from frequent episodes of vertebro basilar insufficiency for 10 years, was admitted because of brainstem ischemic symptoms. Magnetic resonance (MR) images were almost normal, but small flow voids were observed in front of the medulla oblongata and the upper cervical spinal cord. Cerebral angiography revealed that both of the vertebral arteries were completely occluded after branching off the respective posterior inferior cerebellar arteries. The basilar artery was fed only by a retrograde collateral flow via the anterior spinal artery which, arising from the left vertebral artery at the level of the fifth to sixth cervical vertebra, ascended the ventral aspect of the cord. These findings clarified that the flow voids on the MRI were from the anterior spinal artery, and were unusually prominent, as a collateral flow to the basilar artery. To the best of our knowledge, an anterior spinal flow void found on routine brain MR imaging has not been documented in the literature. Our case suggested that the flow void, a very small finding on the MRI, could be a useful sign in the diagnosis of serious vertebral arterial diseases. PMID- 7781218 TI - [Clinicopathological report of cisplatin encephalopathy]. AB - A 61-year-old woman was treated with cisplatin and etoposide for ovarian carcinoma. After the second course of chemotherapy she developed acute encephalopathy which manifested itself as headache, fever, a partial seizure, confusion, and mild right hemiparesis, although no evidence of a central nervous system infection was found. Ten days after the onset of neurological symptoms, she experienced a sudden loss of vision in both eyes. Neurological findings were compatible with cortical blindness. Neurological symptoms subsided and visual acuity completely returned over the next months. The total cumulative dose of cisplatin was 325 mg/m2. She died of aspiration pneumonia on the 43rd day. Postmortem examination revealed severe nerve cell loss, gliosis and spongy changes in the bilateral occipital cortex including visual field, and slight to moderate demyelination in the subcortical white matter of the occipital cortex, Goll's tract, and dorsal root ganglia. As far as we know this encephalopathy is the second report in which the neuropathological changes associated with cisplatin therapy have been demonstrated by autopsy findings. The first was a case report of leukoencephalopathy, which differed significantly from our case in the primary lesions of the brain. We measured the platinum level in several parts of the cerebrum and cerebellum, optic nerve, spinal cord, and cauda equina by using an atomic absorption spectrophotometric technique. Platinum was detected in the bilateral occipital cortex, spinal cord, and cauda equina. These results were consistent with the distribution of pathological lesions. The mechanism of cisplatin-induced focal encephalopathy remains speculative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781219 TI - [A case of facial diplegia in associated with reactivation of herpes simplex virus type I]. AB - A 27-year-old Japanese man developed right peripheral facial palsy after suffering from a cold and low-grade fever for 7 days. Left peripheral palsy developed 4 days later. When he visited our hospital 3 days after that, neurological examination revealed no abnormalities except peripheral facial diplegia. Cerebrospinal fluid (CSF) was normal on admission and on hospital day 12. On admission, the patient had a transient increase of serum titers of HSV type I IgM (fluorescence assay). Then, serum titers of HSV type I IgG (ELISA) continuously increased. A diagnosis of peripheral facial diplegia due to reactivation of HSV type I was made clinically and serologically. Steroid pulse therapy was performed and his facial diplegia disappeared completely after 2 weeks. This case may support the hypothesis of virus etiology of Bell's palsy, and HSV type I should be considered as one of the possible causes of facial diplegia. PMID- 7781220 TI - [The relationship among hematocrit, platelet aggregation and the time of onset in patients with acute stage-cerebral infarction]. AB - We evaluated time relation among hematocrit (Ht), platelet aggregation (PA) and the onset of acute stage-cerebral infarction in 221 patients. Lacunar infarctions were likely to occur in the evening or at midnight. The elevated Ht value was frequently found in patients with infarctions occurring at midnight, suggesting that the elevation of blood viscosity has an intimate etiology to the onset. The decrease of PA was often found in those who suffered from their stroke while awake in the morning or at midnight, and frequently had been associated with elevated Ht in the latter patients. Decrease of PA is often reported during acute stage-cerebral infarction. Our results indicate that increased platelet aggregation may play an important role in developing cerebral infarction, especially in those who had onset of illness in the morning. PMID- 7781221 TI - [Sensory nerve conduction velocity determined by somatosensory evoked potentials in patients with hereditary motor and sensory neuropathy type I]. AB - We evaluated sensory nerve conduction velocity (SCV) determined by somatosensory evoked potentials (SEPs) components in 2 cases of hereditary motor and sensory neuropathy whose sensory nerve action potentials (SNAPs) were not evoked. SEPs elicited by median or ulnar nerve stimulation at the wrist or elbow were recorded from 5 scalp electrodes with ear reference. In both cases, no parietal N20 or frontal P20 component was identified, but a clear parietal P27 component was noted. The onset latency of the P27 component elicited by wrist or elbow stimulation was identified as the point where the superimposed 5 waves diverged. Then, the SCV was obtained by dividing the distance between the wrist and elbow by the onset latency difference. Tibial SCV was also determined by a similar method in one patient. The SCVs of the median, ulnar and tibial nerves were markedly decreased but 10-30% faster than the motor nerve conduction velocities measured concomitantly. We showed that a multichannel scalp recording of SEPs makes it possible to determine the onset latencies of the cortical components. So, SEP testing should be applied to obtain the SCVs in patients whose SNAPs were unrecordable. PMID- 7781222 TI - [Vasomotor impairment in patients with diabetic neuropathy--evaluation by laser Doppler flowmetry]. AB - Using laser Doppler flowmetry, we evaluated cutaneous microcirculation in 28 patients with diabetic neuropathy and 18 control subjects. Skin blood flow in the hand was significantly reduced in the patients compared with that in age-matched controls. Skin blood flow in the hand of the patients correlated significantly with the amplitude of sensory nerve action potential of the median nerve. Significant correlation was shown in the patients between skin blood flow in the hand and changes in systolic blood pressure on standing from a supine position. However, there was no correlation between skin blood flow in the hand and variation in the R-R interval. These results suggest that the skin blood flow may decrease with the progression of diabetic neuropathy, particularly sympathetic autonomic neuropathy, and that neural control may be an important factor in the regulation of skin blood flow. Cold water immersion test revealed that there was no significant difference in vasoconstrictive response during the cold challenge, while recovery time of vasodilatory response after withdrawal of the thermal challenge was significantly prolonged in the patients as compared with that in the controls. In addition, it is suggested that the patients with a small increase or normal in skin blood flow of the hand may possess abnormalities predominantly in vasoconstrictive tone, whereas the patients with a decrease in skin blood flow of the hand in vasodilatory tone. Consequently, microcirculation in skin of extremities changes under the balance of vasoconstrictive and vasodilatory tones in patients with diabetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781223 TI - [A case of carpal tunnel syndrome caused by a ganglion cyst--diagnosis and follow up study with magnetic resonance imaging]. AB - We report a case of carpal tunnel syndrome (CTS) caused by a ganglion cyst which was diagnosed by magnetic resonance (MR) imaging of the left wrist. MR images depicted a 10-mm ganglion cyst which pressed the median nerve toward the ulnar side. The ganglion cyst was punctured under direct endoscopic visualization in the carpal canal, subsequently the clinical and the electrophysiologic findings of CTS improved. The median nerve was delineated in its proper position. MR imaging of the wrist, a noninvasive means to observe median nerve, is useful for the diagnosis and the follow-up study of CTS. PMID- 7781224 TI - [Siblings of early onset cerebellar ataxia with hypoalbuminemia]. AB - Recently, a new syndrome of early onset cerebellar ataxia with hypoalbuminemia (EOCA-HA) was reported in Japan. The clinical features of EOCA-HA overlap with those of Friedreich's ataxia (FA), and primary hypoalbuminemia is a characteristic laboratory finding of this syndrome. Genetic linkage analysis of EOCA-HA including this newly reported family revealed that the gene for EOCA-HA is located on the long arm of chromosome 9 as FA. However, several recombination events were observed between D9S15 in EOCA-HA, whereas no recombination events were seen in FA. We report on two siblings with EOCA-HA and discuss the clinical and laboratory features. The patients were a 25-year-old man (patient 1) and a 23 year-old man (patient 2). Their parents marriage was non-consanguineous. The mode of inheritance is compatible with autosomal recessive mode. Clinically, they showed cerebellar ataxia as the initial symptom in the late infantile period and subsequently showed choreoathetosis and ocular motor apraxia at the age of approximately fifteen years. Deep tendon reflexes were reduced in late infancy and finally disappeared. Amyotrophy and sensory impairment of the legs developed at approximately twenty. Abnormal electrocardiogram and diabetes mellitus were not observed. On X-ray CT scan or MRI, the cerebella of both patients were mildly atrophic. Clinical features in these siblings were indistinguishable from those of ataxia telangiectasia, but immunodeficiency syndrome was absent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781225 TI - [Hemorrhagic cerebral infarction at the old age in a case with familial antithrombin III (ATIII) deficiency]. AB - An old woman had stroke at age 67. Cerebral CT scan disclosed the low-density lesion with high-density area in the left temporal lobe, but no empty delta sign in the superior sagittal sinus. Thereafter, she had sometimes panic attacks. At the age of 70, she was admitted because of loss of consciousness probably caused by the same attack. On admission, Brain CT scan showed no fresh lesions. During the stay in the hospital, she had an episode of deep vein thrombosis of her left leg. The patient was found to have not only reduced biochemical activity but also low immunological level of AT III. Her nephew had also the low plasma AT III antigen concentration. Transesophageal echocardiography showed no abnormality, but atherosclerotic change at the aortic arch. We speculated that hemorrhagic cerebral infarction in the territory of the branch of middle cerebral artery could be induced by the arterial thrombus which was related to the hypercoagulable state associated with familial AT III deficiency, although the possibility of cardiogenic embolic infarction or of cerebral vein thrombosis could not be ruled out. Familial AT III deficiency is one of the causes of cerebral infarction even in the elderly. PMID- 7781226 TI - [MRI study of degenerative process in multiple system atrophy]. AB - The characteristic morphological changes of the brainstem and cerebellar regions of multiple system atrophy (MSA) were studied by MRI in varying subtypes, that is olivoponto cerebellar atrophy (OPCA: 23 cases), striatonigral degeneration (SND: 7 cases) and Shy-Drager's syndrome (SDS: 9 cases). OPCA was characterized by atrophy of the entire regions of the brainstem and the cerebellum. SND and SDS tended to show atrophy similar in type but lessin extent to OPCA. The common lesions in MSA were atrophy of the pontine base and cerebellum, and dilation of the fourth ventricle. Atrophy of the pontine base was more dominant in the inferior part than in the superior part, and cerebellar atrophy was more dominant in the superior part than in the inferior part, indicating that degeneration of the pontocerebellar pathway proceeds principally along fibers connecting the inferior part of the pons and the superior part of the cerebellum. Dilation of the fourth ventricle indicated atrophy of the middle cerebellar peduncle. In almost all the cases of OPCA and about a half the cases of SND and SDS, the pontine base and the middle cerebellar peduncle appeared as high signal intensity on T2 weighted image and as low intensity on T1, suggesting degeneration and demylination. In a few cases of OPCA, the dorsolateral part of the putamen were demonstrated as low signal intensity on T2 weighted image. PMID- 7781227 TI - [Clinical subtypes of essential tremor and their electrophysiological and pharmacological differences]. AB - We divided 19 patients with essential tremor into two subtypes according to clinical characteristics of the tremor. Ten patients had pure postural tremor distributed in the hand(s), head, and face (group A). Nine patients had tremor extending to the voice or leg(s), associated with resting tremor and/or hyperkinesie volitionnelle of the hand(s) (group B). Their ages, the age of onset, and the duration of illness were not different between the two groups. Electrophysiologically, the tremor of group A patients had higher frequencies than that of group B patients, and had synchronized activities for antagonistic muscles. Four of group B patients had reciprocal antagonistic activities of the tremor. Inactive phase of tremor induced by an electrically-evoked muscle twitch was invariably within the range of the physiological silent period for group A patients, and prolonged beyond the range for four of group B patients. Pharmacologically, 78% of group A patients responded well to beta-blocker, which was effective for 25% of group B patients. Sixty per cent of beta-blocker resistant group B patients responded well to phenobarbital. In conclusion, a peripheral mechanism, presumably beta-adrenergic drive, is important for the tremor in group A patients, while central pathogenic mechanisms are more important for the tremor of group B patients. PMID- 7781228 TI - [Scoliosis in the patients with both severe mental retardation and severe physical disability--computed tomography of paraspinal muscles]. AB - Patients with both severe mental retardation and severe physical disability, so called "jushouji", often have scoliosis as one of the complications. The correlation between radiological findings of paraspinal muscles and progression of scoliosis was investigated by computed tomography (CT) in 15 patients. We took the CT of paraspinal muscles at the apical vertebral level in each patient, and measured the size of cross-sectional area and the CT value of paraspinal muscles of the both concave and convex side. There was no significant difference of the size of cross-sectional area of the muscles between the convex and concave side. The average CT value of the muscles was normal on the convex side, but abnormally lower on the concave side. Scattered low density areas were recognized in the fascicles of both sides like moth eaten appearance, which was speculated as fatty tissue. The CT value of remaining muscles was within normal range. The CT value on the concave side became lower as the degree of scoliosis progressed. The group who could not keep sitting position independently showed lower CT value on the concave side and had more severe scoliotic curves than the group who could sit independently or with slight support. From the above results, it may be concluded that the paraspinal muscles of the concave side become secondarily atrophic due to disuse, and may not be responsible for the progression of the scoliosis. PMID- 7781229 TI - [The "pseudo-polyneuropathy" type sensory disturbances in cervical spondylotic myelopathy]. AB - We reported the pseudo-polyneuropathy type sensory disturbances in cervical spondylotic myelopathy. We defined this clinical type by objective superficial sensory deficits of all four distal limbs, and excluded the patients having only subjective sensory disturbances. Ten out of 61 patients with cervical spondylotic myelopathy had sensory disturbances of this type. Two patients noticed difference of the subjective sensations of the upper and lower limbs. Eight patients developed sensory symptoms initially in the upper limbs. Pin-prick sensation was diminished in the upper limbs more predominantly than in the lower limbs. Vibration sense was affected in the lower limbs predominantly. Motor functions were mildly impaired, and muscle stretch reflex of triceps brachii was preserved in all ten patients. Distribution of sensory disturbances of four patients changed in their course. Nerve conduction studies and F-wave latencies were normal. Electromyography showed mild chronic denervation of the C5-C7 innervated muscles. Somatosensory evoked potentials after median or ulnar nerve stimulation showed delayed latencies or attenuated waveforms of N13 as well as P14 peaks. Spinal cord was compressed mainly at C4/5 and C5/6 intervertebral level, shown by myelography, CT-myelography or magnetic resonance imagings. We conclude that the pseudo-polyneuropathy type sensory disturbance of cervical spondylotic myelopathy indicates the lesion at mid-to-low cervical vertebral level. The anatomical substrates for this type of sensory impairment could be caused by combination of the dorsal horn/anterior comissure lesions for the upper limbs, and the anterolateral funiculi lesions for the lower limbs. PMID- 7781230 TI - [Clinical difference between "proximal" and "distal" type of cervical spondylotic amyotrophy]. AB - We studied 31 patients with cervical spondylotic amyotrophy. Weakness and atrophy without prominent sensory changes were started from the proximal muscles in 16 patients (proximal type), and from the distal muscles in 15 patients (distal type). In both types, the age at onset of neurological symptom ranged from thirties to sixties, and men were more frequently affected than women. Distal type patients often presented cold paresis and/or postural finger tremor, which occasionally was the initial symptom. Two patients of proximal type had muscular atrophy extended to the distal end. None of distal type patients had extension of atrophy to the proximal muscles during a long course of their illness. Most patients of proximal type had neurogenic changes on electromyography extended to the distal muscles. Neuroradiologically, proximal type patients had a cord atrophy at C4/5 intervertebral level, and distal type had cord atrophy at C5/6,6/7. We assume that the responsible lesion for the cervical spondylotic amyotrophy is in anterior horn at C5-T1 cord level for the proximal type, and at C7-T1 for the distal type. Abnormal venous circulation within the cord may cause the selective involvement of the gray matter. PMID- 7781231 TI - [Analysis of gait disturbance in a patient with corticobasal degeneration]. AB - A 64-year-old right-handed man was admitted because of increasing clumsiness of the right hand and difficulty in walking since 8 months earlier. The WAIS revealed verbal IQ 124, performance IQ 104 and full scale IQ 115. Neurological examination revealed slight dysarthria and normal eye movements. The right upper extremity showed Gegenhalten, tremor, dystonic elbow flexion, marked grasp reflex, grasping and groping behavior. Voluntary movements were slow and clumsy on the right side. However, neither ideational nor ideomotor apraxia was observed. Tendon reflexes were slightly exaggerated on the right side. Plantar responses were normal. The patient had difficulty in initiating forward walking and turning movements. Once started, he walked dragging his right foot ahead of the left with short steps. A line on the floor was of no benefit. He could not stride across the line on the floor in front of him. Analysis of gait with floor reaction force revealed that the single step rhythm of his frozen gait was about 1.5 Hz, which contrasted with the high frequency seen in Parkinson's disease. MRI demonstrated atrophy of the frontal and parietal lobes on both sides. 123I-IMP single-photon emission CT demonstrated severe hypoperfusion of the left frontal and parietal lobes. Frozen or shuffling gait is a popular symptom as well as unsteady gait and tendency to fall in corticobasal degeneration. It may result from the frontal lobe dysfunction. Lack of improvement in freezing by the visual input contrasts with Parkinson's disease and may be related to dysfunction of the mesial part of the frontal lobe or the parietal lobe involved in corticobasal degeneration. PMID- 7781232 TI - [An autopsy case of intravascular malignant lymphomatosis with intracranial lymphomatous mass lesions]. AB - A 50-year-old man was admitted to our hospital, because of weakness in his right leg. On admission, he had generalized hyperreflexia and positive Babinski signs bilaterally. After admission, weakness in his left leg and confusion developed. A cerebrospinal fluid examination revealed increases in cell counts and protein but was negative for malignant cells. Blood chemistry was normal except for elevated LDH. A bone marrow biopsy yielded lymphoma cells. Successive T2-weighted cranial MRI showed a progressively expanding high signal area in the right parieto occipital lobe. His confusional state improved after chemotherapy; however, two months later another cranial CT showed multiple enhanced mass lesions. The patient died 20 months after the onset of illness. Postmortem examination revealed widespread intravascular aggregates of malignant lymphomatous cells in the cerebrum, lungs and kidney, as well as multiple infarcts without atherosclerosis in the cerebrum. These pathological findings are compatible with those of intravascular malignant lymphomatosis. In addition, extravascularly expanding tumor cells formed multiple nodular lesions in the cerebral hemisphere. An immunohistochemical study showed that the tumor cells were positive for B-cell marker L26. Intracranial lymphomatous mass lesion rarely occurs in cases of intravascular malignant lymphomatosis. In the present case, tumor cells were presumably restricted to intravascular spaces, occluded them and resulted in ischemic lesions in the cerebrum in the early phase, but they expanded extravascularly and developed mass lesions in the terminal stages. In conclusion, intravascular malignant lymphomatosis is considered to be phenotypes of malignant lymphoma. This is the first case of intravascular malignant lymphomatosis associated with intracranial lymphomatous mass lesions in Japan. PMID- 7781233 TI - [A case of "apraxia of eyelid opening" secondary to right hemisphere infarction- assessment of various symptoms of the eye and eyelid]. AB - A 68-year-old right-handed woman showed "apraxia of eyelid opening" during an acute phase of hemorrhagic infarction in the right middle cerebral artery distribution. She showed paradoxical contraction of the bilateral orbicularis oculi muscles both against our order to open her eyes and even against her hand movement to help her eyes open, although she could voluntarily open her eyes. She was diagnosed as "apraxia of eyelid opening". Her eyes kept closed in most of time. Spontaneous blepharospasm and a right conjugate gaze preference were also seen. These symptoms disappeared 2 weeks after the hemorrhagic infarction. Because most of cases in previous reports as well as this patient showed "apraxia of eyelid opening" after a right cerebral involvement, we propose that this symptom may attribute to right cerebral dysfunction. PMID- 7781234 TI - [Development of Wernicke's encephalopathy during the period of oral food intake after a subtotal colectomy for ulcerative colitis]. AB - A 61-year-old woman was hospitalized because of ulcerative colitis which had caused fever, vomiting and diarrhea since June 16, 1992. Then she developed toxic megacolon, and was transferred to our hospital on the 1st of July and underwent subtotal colectomy the same day. After surgery, she received intravenous hyperalimentation (IVH) which contained 1,000 Kcal/day without vitamin supplementation. From the 8th to the 13th post-operative days, she took 3/4 or more of the liquid diet which contained 1,050 Kcal, protein 35 g, carbohydrate 166 g and vitamin B1 0.59 mg per day. From the 14th to the 23rd post-operative days, she ate 4/5 or more of the oral diet which contained 1,700 Kcal/day, protein 68 g, carbohydrate 236 g and vitamin B1 0.93 mg per day. During the 7th to the 23rd day, the IVH was reduced to 800 Kcal and then 500 Kcal per day. She talked less on the 19th post-operative day, and in a few days, her level of consciousness began to decline progressively. On the 27th post-operative day, neurological examinations revealed the following: semi-coma, almost fixed pupils which were 3 mm in diameter, absent doll's eye movement to all directions, flaccid extremities with abolished deep tendon reflexes. Pertinent abnormalities on laboratory data at that time consisted of hemoglobin 7.8 g/dl and serum total protein 5.4 g/dl. Lumbar puncture revealed normal cerebrospinal fluid under normal opening pressure. Cranial magnetic resonance imaging (MRI) taken on the 27th post-operative day demonstrated, on T2-weighted images, symmetrical high intensity lesions in the periventricular areas of the third and fourth ventricles, and periaqueductal area of the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781235 TI - [Cerebral blood flow and metabolism in Lafora disease]. AB - An 18-year-old male manifesting intellectual deterioration and negative myoclonus was diagnosed as Lafora disease by the demonstration of Lafora bodies in the skin and muscle biopsy. The cortical evoked potential to electric stimulation of the median nerve at wrist showed the giant SEP, suggesting hyperexcitability of the sensory motor cortex. Cerebral blood flow, and cerebral glucose and oxygen metabolism were investigated by positron emission tomography (PET) in order to clarify the pathophysiological process in Lafora disease. The result showed diffusely decreased cortical glucose metabolic rate and cerebral blood flow, and moderately lowered oxygen metabolic rate. There was no increase in blood flow or glucose and oxygen metabolism in the sensorimotor cortex in spite of the presence of giant SEP. The ratio of the glucose to oxygen metabolism was not different from the mean value obtained from nine normal subjects. Based on these findings and review of the literature, it is unlikely that there is a significant deficit in cortical energy metabolism in patients with Lafora disease and it would be less plausible to have some enzymatic deficits in glucose metabolic process. PMID- 7781236 TI - [Neuroleptic malignant syndrome associated with the syndrome of inappropriate secretion of antidiuretic hormone]. AB - We reported a case of neuroleptic malignant syndrome (NMS) associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 71-year old woman, who had been diagnosed as hypertension and multiple cerebral infarction, was given sulpiride 150 mg daily for depressive state. Three days after started sulpiride, she developed fever, sweating, difficulty of movement and was admitted to the hospital. The white blood cell count rose to 16,300/mm3 and serum creatine kinase (CK) to 3,063 IU/L. Two days later CK rose to 20,050 IU/L regardless of stopping the drug, so she was transferred to our hospital for further investigation. On admission, it was the 6th day from the onset, she was mute and akinetic accompanied by muscle pain and rigidity in extremities. Serum CK was 1,831 IU/L, Na 122 mEq/L, osmolality 244 mOsm/kg, plasma antidiuretic hormone (ADH) level 6.5 pg/ml and urine Na was 101 mEq/L, osmolality 467 mOsm/kg. Renal and adrenal functions, plasma renin activity were normal. From the history, course and these data, diagnosis of NMS associated with SIADH was made. Intravenous sodium (130-200 mEq/day) and fluids (1,000-1,200 ml/day) were carefully infused. She became active, muscle pain disappeared and rigidity, akinesia decreased. CK, serum Na and osmolality gradually improved to normal. About the transient increase in ADH secretion, we considered that hypothalamic disturbance in NMS might induce leakage of stored ADH from neuroendocrine neurons in it. PMID- 7781237 TI - [Complete deficiency of adhalin (50 kDa DAG) in skeletal muscle of malignant limb girdle muscular dystrophy]. AB - Malignant limb-girdle muscular dystrophy was first described by Miyoshi and co workers in 1966, and has clinical features similar to Duchenne muscular dystrophy but is inherited through an autosomal recessive trait. This paper describes a patient with malignant limb-girdle muscular dystrophy with complete deficiency of adhalin (50 kDa dystrophin-associated glycoprotein (DAG)) in skeletal muscle. The patient was an 11-year-old Japanese girl whose parents were cousin. She learned to walk at one year and 3 months of age. Her gait became unsteady at 3 years of age, and motor dysfunction in the lower extremities progressed thereafter. At 8 years of age, she had difficulty in standing up from a sitting position, but could walk without assistance. At 11 years, she could walk with support, but could not stand up without assistance. Her intelligence was normal. Muscle atrophy was not apparent due to obesity, but her calves appeared hypertrophic. She had generalized muscle weakness, predominantly in the pelvic girdle muscle. Muscle tone was slightly hypotonic, and deep tendon reflexes of the legs were absent or hypoactive. Her sensory system appeared normal. Serum creatine kinase level was elevated to 30 times above the upper limit of the normal range in the patient and normal in her parents. EMG showed a mild myopathic pattern. CT scan of muscle revealed marked low density in the upper legs and mild in the lower legs. Muscle histology showed muscle fiber necrosis with a small number of regenerating fibers. Opaque fibers were occasionally observed, but not as many as in Duchenne type. Fiber splitting was seen frequently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781238 TI - [A case of Kearns-Sayre syndrome whose asymptomatic mother had abnormal mitochondria in skeletal muscle]. AB - The mode of inheritance of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) have not yet been established, since most cases are sporadic. We studied skeletal muscle pathology and mitochondrial DNA (mtDNA) in a sporadic KSS patient (proband) and examined mitochondrial function of the muscle in his asymptomatic family members. The proband was a 56-year-old male with bilateral ptosis, external ophthalmoplegia, retinal degeneration and cardiac conduction disturbance. Biopsied deltoid muscle showed 9.7% of ragged red fibers without cytochrome oxidase (COX) activity and abnormal mitochondria on electron microscopy. Analysis of muscle mtDNA revealed a 4,977 bp deletion between nt. 8,483 and 13,459. None of the family members had symptoms similar to those of the proband. However, an aerobic exercise test of 15W for 15 minutes with an ergometer induced a marked increase in serum lactate levels in the proband's mother. Histology of her biopsied deltoid muscle showed 0.3% of ragged red fibers without COX activity and morphologically abnormal mitochondria. These findings indicate that the abnormal mitochondria of the proband were transmitted from his asymptomatic mother. This also suggests that some of the sporadic KSS/CPEO cases are inherited one. PMID- 7781239 TI - [Oncogenic osteomalacic myopathy; a case report]. AB - A 54-year-old man with oncogenic osteomalacic myopathy was reported. He presented with gradual onset of muscle weakness and painful cramp of the bilateral quadriceps femoris muscles, followed by low inorganic phosphorus, elevated alkaline phosphatase in the serum and hyperphosphaturia. The electromyogram (EMG) revealed myogenic change localized in the quadriceps muscle and nerve conduction study was normal. Muscle biopsy of right vastus lateralis muscle demonstrated non specific myopathic change with minimal neuropathic change: moderate variation in size, many centrally placed nuclei, a few small angulated fibers and pyknotic nuclear clump. The ratio of Type IIA fibers decreased to 5.5%. Serum 25 hydroxyvitamin D and parathormone were normal, whereas 1, 25-dihydroxyvitamin D was above lower normal limit. High dose of 1,25-dihydroxyvitamin D and phosphorus were administered with partial response. CT scan demonstrated tumor in the left 10th rib proximal to the vertebra, invading into the mediastinum. Partial resection of the tumor was performed in order to preserve the rib. Histologically, the tumor was characterized by high vascularity with cystic formation, many giant cells and tumor cells with oval-shaped nuclei. Histopathological diagnosis was primitive mesenchymal tumor (mixed connective tissue variant). Immediately after resecting the tumor, the patient's muscle weakness and painful cramp was prominently relieved and serum inorganic phosphorus and tubular reabsorption of phosphorus became normal, in addition, 1, 25-dihydroxyvitamin D was elevated within normal limit. EMG findings revealed normal motor nerve unit with normal recruitment pattern. Mild myopathy is relatively a common manifestation in patients with osteomalacia. On the other hand, osteomalacia is sometimes caused by tumors, many of which are benign mesenchymal tumors of bone or soft tissue origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781240 TI - [A sporadic dentatorubral-pallidoluysian atrophy (DRPLA) diagnosed by gene analysis]. AB - We report a 48-year-old woman with dentatorubral-pallidoluysian atrophy (DRPLA). She is the only patient in her 15 family members in two generations. She developed cerebellar ataxia and epilepsy at age 43. On admission at 48, she showed mild dementia and choreic movement in her face and extremities as well as truncal and limb ataxia. Routine laboratory examinations were normal. The point mutations in the tRNALys gene of mitochondrial DNA specific for MERRF were not found. A cranial CT scan and MRI showed mild atrophy of the cerebellum and prominent atrophy in the pons, especially in the tegmentum. Although she was thought to have DRPLA from the clinical point of view, absence of family history made the diagnosis difficult. Her parents were healthy until their 80's and died of cerebrovascular diseases and her 5 siblings had no symptoms. Hereditary DRPLA is known as an autosomal dominant disorder, with a high rate of penetrance and low rate of new mutation. According to our recent findings of a CAG repeat expansion in the DRPLA gene, this patient was diagnosed as a sporadic DRPLA. Considering the wide varieties of clinical manifestations, it is essential to examine this gene abnormality for diagnosing sporadic DRPLA. PMID- 7781241 TI - [A case of rigid spine syndrome with congenital cardiac abnormality of sinus venosus defect]. AB - A 28-year-old male with a rigid spine syndrome who had congenital cardiac abnormality of sinus venosus defect was described. The patient was admitted to our hospital because of easy fatigability and palpitation. At the age of 4 years, he had an operation for his congenital cardiac abnormality and developed persistent atrial fibrillation thereafter. On neurological examination, he had average mentality, rigid spine with joint contractures, especially in the left elbow joint, and winged scapulae. He had marked muscle weakness and atrophy, predominantly in the left half of the extremities and trunk. Electromyographic studies demonstrated myopathic with partial neurogenic changes. Motor and sensory nerve conduction velocity was normal. A muscle biopsy specimen obtained from the right rectus femoris showed some marked hypertrophic and atrophic muscle fibers, with prominent internal nuclei, fiber splitting and pyknotic nuclear clump. ATP ase stain showed type 2B fiber deficiency, increased number of type 2C fibers and fiber type grouping. PMID- 7781242 TI - [Guillain-Barre syndrome associated with anti-GalNAc-GD1a antibody subsequent to Campylobacter jejuni enteritis]. AB - We report a 15-year-old man with Guillain-Barre syndrome (GBS) following Campylobacter jejuni enteritis. Neurologic examination revealed distal muscle weakness and mild disturbance of superficial sense on right plantar area. Serial electrophysiologic studies indicated that the predominant process was axonal degeneration of motor nerves. Thin-layer chromatography with immunostaining revealed that serum IgG strongly reacted with GalNAc-GD1a and weakly with GM2, but did not react with GM1. This is the first report of GBS subsequent to C. jejuni enteritis associated with anti-GalNAc-GD1a antibody. PMID- 7781244 TI - [A case of spastic paraparesis, mental retardation and thinning of corpus callosum]. AB - There are several reports of the patients who have peculiar clinical presentation, that is, spastic paraparesis, mental disturbance and thinning of corpus callosum. We presented a sporadic case with similar symptoms. He was born by normal vaginal delivery without problems from consanguineous parents. His development had delayed since his infantile period. He started to have spasticity of the legs at the age 13 years and it worsened with advancing age. On examination at age 19, he was mentally slow, his full-scale IQ being 35. The tone in the arms was slightly increased and marked in the legs. The finger to nose test caused mild dysmetria. Rest of the neurological examinations were normal. MRI demonstrated characteristic thinning of corpus callosum, dominant in anterior portion. In addition, it showed wide cavum vergae and cavum septi pellucidi, and abnormal high intensity in periventricular white matter. The findings of MRI were possibly suggestive of the static developmental disturbance of brain. PMID- 7781243 TI - [A case of radiation neuropathy following radiation therapy for metastasis of breast cancer]. AB - We report a 49-year-old woman with radiation neuropathy, which occurred 7 years after radiation therapy for supraclavicular lymph node metastasis of breast cancer. The patient had noticed a hard induration in the right breast twelve years previously and had a radical operation for right breast cancer. After surgery, she remained well until 7 years ago when she noted a right supraclavicular mass. Based on a diagnosis of metastasis of breast cancer at the right supraclavicular lymph node, she received radiation therapy at 50 Gy in 25 fractions to the lesion. Seven years after radiation therapy, the patient noted muscle weakness of II-V fingers of the right hand, followed by muscle atrophy of the right forearm. We diagnosed her condition as radiation neuropathy based on the absence of a mass lesion in the right supraclavicular region, no RI deposits in that region on Ga and bone scintigraphy, findings supportive of a lesion in the right brachial plexus on EMG and the history of radiation therapy for supraclavicular lymph node metastasis of breast cancer 7 years previously. We treated the patient with pulse therapy with high-dose oral prednisolone. Subsequently, the muscle weakness and atrophy of the right forearm and fingers have improved gradually. We suggest that pulse therapy with high-dose oral prednisolone for radiation neuropathy should be evaluated in a clinical trial, since few therapies are available for this condition. PMID- 7781245 TI - [Thalamic experiential hallucinosis]. PMID- 7781246 TI - Nutritional therapy for pregnant women with a metabolic disorder. AB - Nutritional therapy is essential for a normal reproductive outcome in phenylketonuric women. In homocystinuria, fetal outcome is good in women whose disorder is responsive to vitamin B6 therapy and is poor in women whose disorder is unresponsive to therapy. Pregnancy in galactosemia is rare because of the almost universal ovarian dysfunction present in female patients with this disorder. Transplantation of the fertilized ovum is a promising possibility for these women. In women with MSUD, there has been only one case of pregnancy reported to date. PMID- 7781247 TI - Antenatal ultrasound and fetal Doppler. Diagnosis and outcome in intrauterine growth retardation. AB - Advances in ultrasonographic biometry and fetal Doppler technology enhance our ability to detect the presence of fetal growth retardation, expand our understanding of its pathophysiology, and improve the ability to predict certain outcome parameters. Further refinement of these methods will allow better definition of IUGR as well as a means to more accurately direct perinatal resources. As causes of fetal growth retardation become more precisely defined, improvements in outcome are likely for certain subsets of those populations. PMID- 7781248 TI - Recent advances in parenteral nutrition. AB - With the modifications described in this article, some of the precise elements in parenteral nutrition have been elucidated. With these changes, this form of nutrition has provided the essential calories and trace elements necessary for very-low-birthweight infants, as well as infants who have required surgery. As further research is done in this area, it is anticipated that even more adjustments to parenteral nutrition will be made, in order to provide optimal caloric vitamin, and trace element intake and establish the optimal manner in which these are administered. PMID- 7781249 TI - Metabolic substrates for fetal energy metabolism and growth. AB - This article reviews the basic aspects of fetal nutrition with emphasis on recent developments. Growth and energy requirements are first described, followed by a discussion about the contributions of main metabolic substrates for the fetus including amino acids, carbohydrates, and lipids. While the placenta is not the primary focus of this review, fetal and placental metabolism are intimately related. Current understanding of placental transport and metabolism is included where relevant. Lastly, a current review about the effects of nutrient deprivation on fetal growth and metabolism is presented. PMID- 7781250 TI - Nutritional role of omega-3 fatty acids during the perinatal period. AB - There is now clear evidence that dietary supplementation of omega-3 fatty acid is essential for normal eye and brain development. Corn oil-based diets induce omega 3 deficiency in preterm infants, affecting retinal responses to light, cortical visual evoked potentials, and behavioral measures of visual acuity. Preterm infants require docosahexanoic acid (DHA) because they are unable to form sufficient quantities from precursors provided by soy oil-based formula products. Human milk provides an ideal source of essential fatty acids for premature infants. There is increasing evidence that premature infant formulas containing vegetable oils should be supplemented with long-chain EFAs to promote optimal retinal and cortical visual development. PMID- 7781251 TI - Metabolic balance studies in premature infants. AB - Many investigators over the past three decades have successfully conducted traditional metabolic balance studies in efforts to determine the retention rates of key nutrients important to the optimal growth of preterm infants. Differences in methodologies discussed in this review may explain the inconsistent results of balance studies reported for some nutrients, particularly calcium. These methodologic differences include (1) variability in nutrient intake and nutritional course prior to the balance period, (2) differences in the method of stool collection (with and without markers), (3) use of single versus repeated balance periods, and (4) different durations of balance periods. The data presented here suggest that the variability of net fat absorptions among VLBW infants was decreased when an acclimation period of nutrient intake supportive of growth was provided prior to a metabolic balance study. In addition, the use of markers affected the estimates of net calcium absorption but not fat absorption. Additional factors that may influence net calcium absorption and methods for the estimation of calcium absorption in VLBW infants warrant further investigation. This review describes the methods of specimen collection for metabolic balance studies in VLBW preterm infants that demonstrated reproducible data. The recent application of stable isotope methodology to metabolic balance studies can be extremely advantageous in identifying the rates of nutrient absorption versus endogenous secretion in the GI tract. PMID- 7781252 TI - Minimal enteral feedings. AB - The provision of early minimal enteral nutrition to the metabolically stable premature infant appears to result in multiple nutritional benefits and in a minimal risk of complications. Whereas benefits can be achieved with feeding volumes ranging from 0.1 to 4 mL/kg, future studies will need to address the responses of the immune system, the circulatory system, and motor activity of the intestine to various feeding regimens before pragmatic recommendations can be concluded. PMID- 7781253 TI - Suitability of human milk for the low-birthweight infant. AB - Information is emerging now that supports the use of human milk for low birthweight (LBW) infants. The nutritional benefits, in terms of protein digestion, amino and fatty acid patterns, fat absorption, and lactose digestion are recognized. Gastrointestinal function may be enhanced with human milk feeding. Profound effects on host defense, including a reduction in the rates of neonatal infection and necrotizing enterocolitis, recently have been acknowledged. To enable the LBW infant to continue to receive a mother's own milk, attention needs to be focused on specific nutrient limitations. Calcium and phosphorus require supplementation. Protein and sodium supplements may be needed. Commercial formulations are available that enable the fortification of human milk. Approaches that facilitate the feeding of a mother's own milk should be adopted by neonatal units. PMID- 7781254 TI - Trace elements in nutrition for premature infants. AB - Ten trace elements that are nutritionally essential include: zinc, copper, selenium, chromium, manganese, molybdenum, cobalt, fluoride, iodine, and iron. This article briefly reviews the biochemistry of these trace elements, describes clinical deficiency states, and provides a rationale for recommended enteral and parenteral intakes for preterm infants. PMID- 7781255 TI - Gastrointestinal motility in the neonate. AB - Although patterns of gastrointestinal movements have been recognized for nearly a century, only in the past 10 years have we had the diagnostic tools to characterize both normal and abnormal motility in the neonate. Parallel with these advances, over the past 25 years, we have seen an explosion in our understanding of the ENS and its independent regulation of gut motility. It is expected that, as we come to a better understanding of the microregulation of intestinal motor activity, we can develop more effective means to treat many of these heretofore refractory disorders of gastrointestinal motility. PMID- 7781256 TI - Nutritional care of the extremely premature infant. AB - In summary, the nutritional care of extremely premature babies includes special attention to glucose homeostasis and fluid and electrolyte balance in the immediate postnatal period. Parenteral nutrition should be started routinely on the 2nd or 3rd day of life, if the infant is metabolically stable, and continued until the infant is receiving sufficient enteral feedings to promote growth. If not clinically contraindicated, minimal enteral feedings should be started before the end of the first week of life. The decision to either advance or maintain minimal enteral feedings at a constant level should take into account the clinical status of the infant. Fortified preterm human milk is the preferred feeding and premature infant formulas, the best substitute. Multivitamin supplements may be necessary, depending on formula intake. Iron supplements can be initiated as early as 2 weeks of age and high levels of intake appear to be necessary during erythropoietin therapy. PMID- 7781257 TI - The effects of illness on neonatal metabolism and nutritional management. AB - In summary, careful attention to nutrient delivery in the IUGR infant is important to prevent and treat neonatal metabolic derangements and to improve postnatal growth. Carbohydrates are the essential fuel in the first days of life, to prevent hypoglycemia. Subsequent delivery of protein and fat helps rectify reduced muscle and fat stores and promotes weight gain. Calcium supplementation to prevent further bone demineralization and iron supplementation to replete iron stores may be necessary. Of special interest is that the neurologic outcome of these infants appears linked to the rate of catch-up growth. The rate of postnatal head growth depends on many perinatal and neonatal risk factors, and is a strong predictor of early developmental outcome in low-birthweight infants. Insufficient energy delivery beyond 2 weeks postnatal age in SGA premature infants results in failure to initiate subsequent catch-up head growth, with consequently smaller head circumferences at 1-year follow-up. PMID- 7781258 TI - Stable isotopes as metabolic probes for nutritional studies in neonates. AB - Metabolic and nutritional studies with stable isotope tracers have proved valuable in the human newborn. This technique is acceptable ethically, because it does not expose the infant to radioactivity, and it is sensitive enough for the analysis of very small samples. The stable isotope method has been especially applied to studies of neonatal carbohydrate, protein, and energy metabolism. PMID- 7781260 TI - Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing. AB - Pharmacokinetics and pharmacodynamics of pimobendan were studied in eight patients with dilated cardiomyopathy and chronic congestive heart failure after single dosing and after 2-week repeated dosing of 5 mg racemic pimobendan. Enantiomers of pimobendan and its demethylated metabolite in plasma and in red blood cells were measured. In the single-dose study, the peak plasma levels of 16.3 +/- 4.0 and 17.0 +/- 3.1 ng/ml of (+)- and (-)-pimobendan were observed at 0.9 hour after dosing. The concentration-time curves followed a two-compartment model, with terminal half-lives of 2.56 +/- 0.35 and 2.93 +/- 0.33 hours for (+)- and (-)-pimobendan (p > 0.05), respectively. The oral volumes of distribution after equilibrium were 3.26 +/- 0.74 and 3.13 +/- 0.75 L/kg, and oral clearances were 28.6 +/- 7.0 and 21.9 +/- 4.1 ml/min/kg for (+)- and (-)-pimobendan (p > 0.05), respectively. In red blood cells, the respective (+)- and (-)-pimobendan concentrations were 5.8 and 8.4 times higher than those in plasma, indicating a stereoselective partitioning of drugs between plasma and red blood cells. The pharmacodynamic effect of pimobendan was evaluated by echocardiography. The ejection fraction, mean velocity of circumferential fiber shortening, aortic flow peak velocity, cardiac index, and stroke volume index significantly increased 50% to 60%. The left ventricular end-systolic dimension, systolic blood pressure, and diastolic blood pressure significantly decreased 8% to 11%. These effects lasted for more than 8 hours. In a 2-week repeated-dose study, there was no significant dose accumulation in plasma and red blood cells. The pharmacokinetic parameters were similar to those in the single-dose study, except for significantly shorter absorption half-lives. The baseline levels of cardiac index and stroke volume index were significantly higher than the baseline levels in the single-dose study. This suggests an accumulation of pharmacodynamic effects despite a relatively short elimination half-life. PMID- 7781259 TI - Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. AB - The bioavailability, pharmacokinetics, and pharmacodynamics of torsemide (10 mg orally and intravenously) and furosemide (40 mg orally and 20 mg intravenously) were determined in a randomized crossover clinical trial in 16 patients with compensated congestive heart failure. Torsemide (time to reach maximum concentration [tmax], 1.1 +/- 0.9 hour) was more rapidly absorbed than furosemide (tmax, 2.4 +/- 2.5 hours), the absorption of which was delayed compared with that in healthy volunteers. Bioavailability of torsemide was also greater and less variable than that of furosemide. All four treatments yielded comparable changes from baseline in 24-hour electrolyte excretion. Based on the relationships between sodium excretion rate and fractional sodium and urinary drug excretion rate, response to both diuretic agents at the level of the nephron was decreased compared with previous studies with healthy subjects. Assessment of the clinical relevance, if any, of the difference in the variability of absorption warrants further study. PMID- 7781261 TI - Population pharmacokinetics of the active metabolite of nabumetone in renal dysfunction. AB - We determined the pharmacokinetics of 6-methoxy-2-naphythylacetic acid (6-MNA), the active metabolite of nabumetone, in normal subjects and in subjects with impaired renal function, including subjects requiring hemodialysis. Subjects received a 1000 mg oral dose of nabumetone either as a single dose or daily for 15 days. We used a noncompartmental pharmacokinetic analysis and compared those results to a population pharmacokinetic analysis performed with nonlinear mixed effects modeling (NONMEM). The results of the two different analyses were similar. The elimination half-life increased with decreased renal function and ranged from 22 to 44 hours. The area under the curve decreased significantly at steady state, regardless of renal function. The apparent clearance determined by NONMEM analysis increased from 0.68 L/hr after a single dose to 1.13 L/hr at steady state. The apparent volume of distribution was directly proportional to the nonalbumin protein concentration and ranged from 23 to 60 L. We conclude that the pharmacokinetics of 6-MNA in this population are complicated by possible protein binding changes. However, the increased half-life in patients with renal failure is offset by changes in the apparent volume of distribution that prevent the accumulation of 6-MNA in the serum of patients with impaired renal function. Therefore dosage adjustments may not be necessary in patients with decreased renal function. PMID- 7781262 TI - Pharmacokinetics of the novel antiestrogenic agent toremifene in subjects with altered liver and kidney function. AB - OBJECTIVES: The pharmacokinetics of toremifene was investigated in an open study with four parallel groups of 10 subjects each. Subjects with impaired liver function (biopsy-proven liver disease), activated liver function (drug-induced), and impaired kidney function were compared with normal subjects. METHODS: A single oral 120 mg dose of toremifene was administered after an overnight fast, and blood samples were collected over 28 days. Serum levels of toremifene and its metabolites were determined; appropriate pharmacokinetic parameters were calculated and statistically evaluated. RESULTS: In normal subjects, the average peak level of 414 ng/ml toremifene was achieved at 3 hours after dosing, the terminal half-life was 6.2 days, apparent oral clearance was 5.1 L/hr, apparent volume of distribution was 958 L, and the fraction not bound to protein was 0.3%. The peak level (130 ng/ml) of the major metabolite, N-demethyltoremifene, appeared in serum with large variation in the time to peak level (median, 3 days) and a terminal half-life of 21.0 days. Low levels of deaminohydroxytoremifene were also measured, and two other metabolites could be quantified at some time points in some patients. The elimination rate of toremifene and the main metabolite was significantly increased in patients with activated liver function, resulting in decreased terminal half-lives (3.0 days and 4.5 days, respectively), and was decreased in patients with impaired liver function (10.9 days and 29.6 days, respectively). The subjects with impaired kidney function showed normal elimination kinetics. CONCLUSION: Liver, but not kidney, function should be taken into account when toremifene is administered. PMID- 7781263 TI - Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly. AB - Ibuprofen is an over-the-counter nonsteroidal anti-inflammatory drug with a low incidence of severe adverse reactions. It is metabolized by oxidation to carboxyibuprofen and hydroxyibuprofen and by conjugation to an acyl glucuronide. In vitro studies have indicated that ibuprofen glucuronide is labile and reactive, forming covalent adducts with proteins. To verify the formation of ibuprofen-protein adducts in vivo, the pharmacokinetics of ibuprofen glucuronide and its covalent binding to plasma proteins were studied in five elderly patients who received long-term administration of oral doses of ibuprofen. Plasma levels of ibuprofen glucuronide were low relative to those of ibuprofen; the ratio of area under the plasma concentration versus time curve for the glucuronide relative to the parent drug was only 4%. Covalent binding of ibuprofen to plasma protein was observed in all patients, correlating well with the area under the plasma concentration versus time curve of ibuprofen glucuronide (r = 0.966). Compared with reports for other nonsteroidal anti-inflammatory drugs that form acyl glucuronides, plasma levels of ibuprofen-protein adduct are low during long term administration. The observed lower reactivity in vivo is probably attributable to the greater stability of ibuprofen glucuronide relative to other acyl glucuronides. PMID- 7781264 TI - Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. AB - Chlorzoxazone 6-hydroxylation is mediated by CYP2E1, and its measurement provides an in vivo probe of the enzyme's activity. To determine the population distribution of such activity, the disposition of chlorzoxazone and its 6-hydroxy metabolite was determined after oral administration to 70 white subjects (40 men and 30 women) residing in middle Tennessee. Both oral (330 +/- 111 ml.min-1, mean +/- SD) and fractional (213 +/- 86 ml.min-1) clearances varied fourfold to fivefold within the population and were unimodally distributed in a visually normal fashion. Clearance values were one-third greater in men than in women, but such differences were less striking after normalization according to body weight. Attempts to develop a single-time-point measure of 6-hydroxylating ability on the basis of plasma levels or urinary excretion of chlorzoxazone or its metabolite were unsuccessful. Genetic polymorphisms (Pst I and Rsa I restriction fragment length polymorphisms) in the 5'-flanking region of CYP2E1 deoxyribonucleic acid obtained from peripheral leukocytes were not associated with differences in the disposition of chlorzoxazone. Similarly, no major effects on 6-hydroxylation were associated with mutations in intron 6 associated with a Dra I restriction fragment length polymorphism. The interindividual variability in CYP2E1 activity as measured in vivo in healthy subjects appears to be considerably less than that expected based on in vitro studies. Whether such variability is associated with individual susceptibility to CYP2E1-mediated toxicity remains to be determined. PMID- 7781265 TI - Phenotyping and genotyping of S-mephenytoin hydroxylase (cytochrome P450 2C19) in a Shona population of Zimbabwe. AB - The S-mephenytoin hydroxylase has recently been identified as cytochrome P450 2C19 (CYP2C19). This enzyme metabolizes mephenytoin, diazepam, omeprazole, and citalopram and has been shown to be polymorphically distributed. One clinical implication of CYP2C19-dependent drug metabolism for persons who reside in tropical regions is in the use of the antimalarial drug chloroguanide hydrochloride, which is apparently biotransformed to its active metabolite by this isozyme. In this investigation we studied mephenytoin metabolism in 103 black Zimbabwean Shona subjects. Four were identified as poor metabolizers (4%). This prevalence is comparable to that in white subjects (2% to 5%) but lower than the 15% to 20% incidence of poor metabolizers among Oriental subjects. Of the subjects phenotyped, 84 were genotyped for the G-->A mutation in exon 5 of CYP2C19, which creates a cryptic splice site, causing the production of a nonfunctional protein. Three of the four poor metabolizers were homozygous for this mutation, whereas the fourth one was heterozygous. The G-->A mutation has been shown to predict the incidence more than 60% of poor metabolizers among white subjects and Japanese subjects, and in the current investigation we also obtained a similar relationship in the black population. PMID- 7781266 TI - The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: a population study. AB - We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism. Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers. Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection. Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing. All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance. Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r2 = 0.681; p < 0.001). Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism. PMID- 7781267 TI - Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study. AB - The reversible monoamine oxidase A inhibitor moclobemide was given in single (300 mg) and multiple doses (600 mg/day) to 11 male and four female healthy volunteers (age range, 23 to 27) who were either poor metabolizers of S-mephenytoin (n = 7) or extensive metabolizers of S-mephenytoin (n = 8). All were extensive metabolizers of sparteine. Poor metabolizers of S-mephenytoin had lower moclobemide clearance values (median, single dose: 16.1 versus 43.2 L.hr-1; steady state: 13.4 versus 22.1 L.hr-1) and longer moclobemide half-life values (median, single dose: 4.0 versus 1.8 hours; steady state: 5.1 versus 2.7 hours) than extensive metabolizers of S-mephenytoin. The plasma levels of a metabolite formed by C-hydroxylation (Ro 12-8095) were lower in poor metabolizers of S mephenytoin than in extensive metabolizers of S-mephenytoin. Moclobemide thus partially undergoes oxidative metabolism by way of the polymorphic CYP2C19. A combined mephenytoin, sparteine, and caffeine test performed before, during, and after multiple dosing of moclobemide showed changes in the metabolic indexes compatible with a reversible inhibition of oxidation by way of the corresponding CYP enzymes--CYP2C19, CYP2D6, and CYP1A2--during moclobemide treatment. PMID- 7781268 TI - Racial differences in sensitivity to the negative chronotropic effects of propranolol in healthy men. AB - OBJECTIVE: Dose-response studies in patients with hypertension have shown that black subjects are less responsive to beta-blocker therapy than white subjects, whereas studies in healthy volunteers suggest marginal or no racial differences in response. No concentration-response studies have been conducted in black subjects and white subjects. The purpose of this study was to characterize beta blocker pharmacodynamics in healthy black and white men. METHODS: Thirteen black and 13 white healthy men took 80 mg oral propranolol three times daily, for a total of 16 doses. Heart rate response to treadmill exercise was measured at various times over 24 hours. Serum propranolol samples were collected during the same 24-hour time period and were measured by chiral HPLC. The sigmoid maximal effect (Emax), Emax, and linear models were fitted to percentage reductions in exercise heart rate and S-propranolol concentrations. RESULTS: Black subjects had significantly lower values for serum concentration producing one-half the maximal effect (EC50) and unbound EC50 than white subjects (EC50: 10.2 ng/ml (4.4 to 28.0 ng/ml) versus 24.4 ng/ml (14.3 to 64.1 ng/ml), blacks versus whites; unbound EC50: 1.29 ng/ml (0.686 to 4.91 ng/ml) versus 2.77 ng/ml (1.70 to 8.11 ng/ml), blacks versus whites). There was no statistical difference in Emax (33.3% [22.2% to 39.7%] versus 38.3% [30.7% to 45.1%], blacks versus whites). CONCLUSIONS: Healthy black men were more sensitive to beta-blockade than healthy white men. The results of this study in healthy volunteers suggest that the racial differences in response observed in patients with hypertension are related to hypertensive pathophysiology rather than normal physiology. PMID- 7781269 TI - Regional brain glucose metabolism after acute alpha 2-blockade by idazoxan. AB - BACKGROUND: Several classes of antidepressant drugs act on alpha 2-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha 2-binding and in vivo responses mediated by alpha 2-receptors. Measurement of regional brain metabolic response to an alpha 2-antagonist may be a useful method for further definition of the role alpha 2-receptor regulation plays in the treatment of neuropsychiatric disorders. METHODS: Regional brain glucose metabolism was measured before and after infusion with 200 micrograms/kg idazoxan with use of 18F-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured. RESULTS: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response. CONCLUSIONS: Our findings are consistent with regionally specific effects of alpha 2-blockade. This method may be useful for the study of alpha 2 receptor function in humans. PMID- 7781270 TI - Pemoline-associated fulminant liver failure: testing the evidence for causation. AB - BACKGROUND: Pemoline is a central nervous system stimulant used in treating children with attention deficit-hyperactivity disorder. Hepatotoxicity has been commonly reported in association with pemoline; however, only two reports of cases of fatal liver failure have been published. OBJECTIVES: We report on a 14 year-old boy who received concomitant pemoline and methylphenidate in whom fulminant liver failure occurred and for whom liver transplantation failed. Other causes of fulminant liver failure were ruled out, and the liver biopsy was suggestive of drug toxicity. We estimated the probability that these three cases represent an increased risk of fulminant liver failure associated with pemoline. RESULTS: Based on the three known cases of fatal liver failure associated with pemoline use, we calculated that a child receiving pemoline has a relative risk of development of fulminant liver failure of 45.3 (95% confidence interval, 4.1 to 510). This highly significant association (p < 0.001) suggests causation. CONCLUSIONS: Because pemoline has been widely used in recent years, further studies are needed to better quantify this risk in children with attention deficit-hyperactivity disorder. PMID- 7781271 TI - Buspirone and electroencephalography. PMID- 7781272 TI - Laboratory evaluation of platelet dysfunction. AB - Platelet dysfunction, especially acquired forms, is a common cause of hemorrhage, especially when associated with trauma or surgery. Although the hereditary platelet function defects are generally rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients with easy and spontaneous bruising, mild-to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the face of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable, and platelet aggregation or lumi-aggregation should be done in applicable clinical situations. Prolongation of the template bleeding time is an unreliable predictor of clinical bleeding propensity. The mainstay of therapy for all of these defects, if bleeding is important, is the liberal infusion of suitable numbers of platelet concentrates. The acquired platelet function defects should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should immediately be stopped. PMID- 7781273 TI - Laboratory monitoring of unfractionated heparin treatment. AB - Laboratory monitoring is indicated when unfractionated heparin is used in the treatment of established thromboses. Special problems may be encountered in patients with antithrombin III alteration, thrombocytopenia, heparin resistance, or with an increased risk of bleeding. PMID- 7781274 TI - Contemporary laboratory monitoring of low molecular weight heparins. AB - Low molecular weight heparins are widely used in the prophylaxis and treatment of thromboembolic accidents. Laboratory monitoring seems restricted to the treatment of established thrombosis. Repeated controls of platelet count are mandatory. PMID- 7781275 TI - Blood protein defects associated with thrombosis. Laboratory assessment. AB - This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore, these are the defects which should first be searched for in an individual with unexplained thrombosis. If these more common defects are not found, the rarer defects, including HC-II, plasminogen, or TPA deficiency, dysfibrinogenemia, elevated PAI-1, or heterozygous homocystinemia should be looked for. The incidence of activated protein C co-factor deficiency (APC resistance) is not yet clear but may also represent a common defect. PAI-1 defects may, with time, be shown to be common. Finding these defects has important implications for therapy for the individual patient and for the institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks for thrombosis. PMID- 7781276 TI - Laboratory monitoring of thrombolytic therapy. AB - The concept and strategy of thrombolytic therapy are absolutely correct. The obstructing intraluminal thrombus is in urgent need of resolution to permit reestablishment of blood flow. As investigative efforts in this area continue, more effective and more rapidly acting thrombolytic agents will be forthcoming. The thrombolytic agents available today are excellent and can definitely be used safely. However, a modicum of common sense must be employed in initiating their use. There must be frequent contact with the patient receiving such important and needed therapy. It is foolish for those individuals either not familiar with or not educated to utilize thrombolytic agents to make broad sweeping statements that such agents, whose efficacy has been demonstrated, should not be employed in the treatment of thrombosis. Such an attitude is an example of how not to proceed to further improvement in health care. To be content to remain in the past will never permit entrance into the future. PMID- 7781277 TI - Economic tools for the pathologist. AB - Whether or not it is generally accepted by medical care personnel within the hospital or the laboratory, the laboratory is a business within a hospital. If the laboratory is free-standing, with a corporate ownership, then a laboratory is a business by itself. Even if it is a part of a nonprofit organization (more than two thirds of American hospitals are nonprofit), a laboratory must be able to generate more gains (profits, assets, contribution margin) than losses (liabilities, costs). With the growing volume and complexity of laboratory tests in the United States, the onerous surge of regulatory restrictions, decreasing capital, decreasing physician's reimbursement, increasing salary and operating costs, it is now time for the pathologist to add new tools to his/her customary "tools of the trade," such as surgical knives, microtomes, analyzers, and microscopes. These new tools are the economic tools of cost analysis, productivity analysis, ratio analysis, utilization review, and capital asset analysis. The pathologist of the future must not only provide patient care diagnostic expertise, but must also be a successful manager of human, fiscal, and operational resources to survive in an economic environment that demands knowledge of the principles of successful laboratory management. In addition to a general review of economic and financial "tools," this article describes techniques that have been developed during the past several years by the Laboratory Fiscal Management Committee of the College of American Pathologists that analyze, condense, and interpret general macro-indicators of laboratory cost and operational functions. These indicators are generic and can be quickly understood and utilized by every pathologist practicing in a private, commercial, or public laboratory setting. PMID- 7781279 TI - The antiphospholipid and thrombosis (APL-T) syndromes. Clinical and laboratory correlates. AB - Anticardiolipin antibodies and the lupus anticoagulant are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanisms by which antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with anticardiolipin antibodies are deep venous thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular-retinal vessel thrombosis (type III syndrome); occasionally, patients present with mixtures (type IV syndrome). The relative frequency of anticardiolipin antibodies in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be measured. Also, the type of syndrome (I through V) should be defined, if possible, as this may dictate both the type and duration of both immediate and long-term anticoagulant therapy. Unlike patients with anticardiolipin antibodies, patients with primary lupus anticoagulant thrombosis syndrome usually sustain venous thrombosis. Because the aPTT is unreliable in patients with lupus anticoagulant (prolonged in approximately 40% to 50% of patients) and is seldom prolonged in patients with anticardiolipin antibodies, definitive tests (ELISA for anticardiolipin antibodies and the dRVVT for lupus anticoagulant) should be immediately ordered when antiphospholipid syndrome is suspected or when individuals present with otherwise unexplained thrombotic or thromboembolic events. PMID- 7781278 TI - Molecular markers of hemostatic activation. Implications in the diagnosis of thrombosis, vascular, and cardiovascular disorders. AB - Until recently, the diagnosis of thromboembolic disorders remained difficult to establish before the occurrence of a pathologic event. Clearly, thrombosis is the result of a progressive alteration of the blood and vasculature. Various molecular markers of hemostatic alteration are found in increased or decreased amounts predisposing to thrombosis or in increased circulating amounts during the activation process. PMID- 7781280 TI - Laboratory diagnosis of antiphospholipid syndromes. AB - The search for clinical outcomes associated with antiphospholipid antibodies (aPL) has been ongoing for a decade. This article focuses on the clinical use of tests for the detection of aPL. A review of the current thinking regarding the pathophysiology of antiphospholipid syndromes is relevant to the discussion of different aPL assays and methodologies. The value of aPL testing in specified patient populations is analyzed. PMID- 7781281 TI - Whose enlightenment? Medicine, witchcraft, melancholia and pathology. PMID- 7781282 TI - Sarah Stone: enlightenment midwife. PMID- 7781283 TI - Developing medical expertise: medical practitioners and the suspected murders of new-born children. PMID- 7781284 TI - Reflections on medical reform: Cabanis' Coup d'CEuil. PMID- 7781285 TI - The enlightenment encountered: the German Physicus and his world, 1750-1820. PMID- 7781286 TI - Conflicting attitudes towards inoculation in enlightenment Germany. PMID- 7781287 TI - Honeyed words: Bernard Mandeville and medical discourse. PMID- 7781288 TI - Shaping psychiatric knowledge: the role of the asylum. PMID- 7781289 TI - Vitalism, disease and society. PMID- 7781290 TI - The weight of evidence and the burden of authority: case histories, medical statistics and smallpox inoculation. PMID- 7781291 TI - Methodism and Dr George Cheyne's 'more enlightening principles'. PMID- 7781293 TI - An enlightenment science? Surgery and the Royal Society. PMID- 7781292 TI - Anti-Lockean enlightenment?: mind and body in early eighteenth-century English medicine. PMID- 7781294 TI - The politics of committal to early modern Bethlem. PMID- 7781295 TI - Medical reform, the enlightenment and physician-power in late eighteenth-century France. PMID- 7781296 TI - Microbiological assessment of denture hygiene among patients in longstay and daycare community places. AB - A simple, inexpensive microbiological assay for objective measurement of denture hygiene has been devised. Small individual filter paper discs were applied to the fitting surface of dentures for 20 seconds, eluted in phosphate buffered saline and bacterial counts on blood agar plates performed on the eluate. There was a strong positive correlation between denture cleanliness (graded on a scale of 0 to 4) and both total anaerobic count (r = 0.829; P < 0.001) and total aerobic count (r = 0.786; P < 0.001) following logarithmic transformation. Yeasts in the eluted disc specimens could be used as an aid to diagnose oral candidiasis. The method provided an objective measure of denture hygiene among elderly patients in longstay hospitals and daycare community places. It may be applicable to audit studies following implementation of new oral health care policies. PMID- 7781297 TI - Changes in dental attitude and behavior among Dutch adults wearing complete dentures. AB - In 1992 a follow-up on the Dutch National Dental Survey of 1986 (DNDS) was performed. The main objective was to detect and analyze changes in oral self care, dental attendance, and oral health status. This paper will focus on the DNDS adults wearing complete dentures. Changes over a 6-yr period will be presented of: dental attendance, denture satisfaction and wearing of the complete dentures, and denture treatments. A postal questionnaire was used: 232 persons (64%) participated in the study. Analysis of Variance (ANOVA) was used to study the effect of dental and social variables on observed changes since 1986. Risk ratios (RR) were computed to clarify the actual effects of these variables. With respect to dental attendance, a shift towards visits for denture check-ups was found, thought to reflect the respondents' concern for their complete dentures (RR = 1.6). A small shift towards more visits because of denture problems was found. This was attributed to denture treatments that had taken place between 1986 and 1992 (RR = 2.8). With respect to changes in denture satisfaction, no influence of denture treatments could be noted, but a relation was found with a variable indicating the imperfection of the complete dentures as felt by the respondents (RR = 2.8). In 31% of the respondents some denture treatment had been performed since 1986. No objective dental criteria of complete dentures and denture bearing areas had influenced these denture treatment decisions, but only respondents' subjective criteria (RR = 1.9-2.9). PMID- 7781298 TI - Characteristics of 5410 edentulous implant candidates and the treatment they receive. AB - Since 1989 implant dentistry in the Netherlands is a National Dental Insurance (NDI) benefit, thus reducing out-of-pocket expenditures for implant candidates considerably. A nationwide investigation was set up in order to evaluate quantitative, qualitative and financial effects of this new provision. The patient and treatment characteristics of 5410 edentulous implant candidates are discussed. Intensive monitoring of the usage of these new regulations facilitates health care policy making, including future planning. Over a 3 1/2 yr period, two out of every thousand totally edentulous NDI patients were treated in combination with dental implants. This number is being considered small, bearing in mind the number of edentulous patients in the Netherlands and the proportion of dissatisfied denture wearers. Demographic data, prosthetic and pre-prosthetic surgical history reveal that these patients, mostly female and middle-aged, experience severe denture-related problems. In the majority of cases the implants are placed by an oral surgeon and the suprastructure is made by a general dentist or at a centre for special dental care. The treatment itself mostly consists of an implant retained overdenture on two or four permucosal implants and a bar construction. PMID- 7781299 TI - General and local contraindications for endosseal implants--an epidemiological panoramic radiograph study in 65-year-old subjects. AB - In order to evaluate general and local contraindications for implantation for 65 yr-old subjects from a medium-sized Finnish city, 431 such persons were examined anamnestically and by means of panoramic radiographs. The population represents 61% of the total age group in the city (born in 1923). It was shown that several degrees of cardiac problems and increased blood pressure followed by pulmonary diseases and diabetes were the most commonly encountered relative contraindications for implantation. Eleven percent of the patients said that they smoked regularly and the bone quality was estimated to be less suitable for implantation in 21% of the cases. Implantation was evaluated according to the Bonefit system (implant lengths between 6 and 16 mm) in 10 regions in the maxilla and 6 regions in the mandible and was shown to be possible in 38% of the regions in the partially edentulous maxillae and 50% of those in the partially edentulous mandibles, the corresponding figures for the edentulous jaws were 55% in the maxilla and 61% in the mandible. PMID- 7781301 TI - Mutans streptococci, lactobacilli and caries experience in 12-year-old Icelandic urban children, 1984 and 1991. AB - In order to evaluate changes in salivary counts of cariogenic bacteria and relate these to trends in caries experience, stimulated saliva was collected from a 20% random sample of 12-yr-old residents of Reykjavik, Iceland (252 children) in 1991 under conditions consistent with those of a survey conducted in 1984. The mean and median counts of salivary mutans streptococci and lactobacilli remained similar in the two studies. However, the frequency distribution at lower levels of mutans streptococci differed significantly between 1991 and 1984, e.g. in the present study 25.8% of the children had < 10(5) compared with 13.8% in the study 1984. The mean caries prevalence in the permanent dentition (DFStot) was 11.0, which is significantly lower than in 1984 (mean DFStot 28.8). A significant difference in caries prevalence was found at various levels of salivary mutans streptococci. Strep. mutans (serotype c/e/f) was carried by all mutans streptococci-positive children, save one child, who carried only Strep. sobrinus. The proportion of 12-yr-olds who carried Strep. sobrinus had decreased significantly to 15.7% from 34.0% in 1984. Significantly more children with Strep. sobrinus showed high levels of total mutans streptococci than children with only Strep. mutans. As the case was in 1984 significantly more Strep. sobrinus carriers had a high level of salivary lactobacilli as well as higher caries prevalence than the children who did not carry this species. PMID- 7781300 TI - How is oral health education conducted in Finnish health centers? AB - The oral health education (OHE) given in Finnish health centers is mostly implemented by dental assistants and hygienists. However, there is no exact information concerning the distribution of OHE work and the working methods among individual health educators. The aims of this study were to assess 1) the time used for OHE by the dental professionals who bear most of the responsibility for OHE in health centers, and to evaluate 2) the collaboration between OH-educators and the parents of schoolchildren, school personnel and the other health care personnel and 3) the sources of the OHE knowledge and skills of these OH educators and their methods according to their work load. The data for this study were collected from 323 OH-educators. About one fourth (28%) of the OH-educators used 40% or more of their working time for group OHE and one third (33%) used 40% or more of their time for individual OHE. These workers were considered to be full-time OH-educators. The mean age of the OH-educators was 36 yr. The mean length of the OHE career was 8 yr. The most common OHE methods were a usual type of school lesson or a lesson in which the audience was questioned. Slides, models, transparencies and leaflets were the most general visual aids used. PMID- 7781302 TI - Dental caries and dental registration status in nursery school children in Newry, Northern Ireland. AB - 294 children aged 2-4 yr attending nursery schools in Northern Ireland were examined for dental caries and dental registration status under the capitation system in general dental practice. Their mean age was 3 yr 10 months. Sixty eight per cent were caries free, mean dmft was 1.10 and dt, mt and ft scores were 0.74, 0.28 and 0.09, respectively. With increasing age the prevalence of caries increased, though the very low care index (d/dmft) did improve in the older children. Seventy per cent reported being registered for dental care and their levels of dental caries were significantly higher than those who were not yet enrolled (P < 0.001). For those not enrolled for dental care the main perceived barriers to seeking care related to lack of symptoms (33.6%) and apathy (31.6%) while few reported fear as a barrier (4.5%). PMID- 7781303 TI - Prevalence and distribution of developmental enamel defects in primary dentition of Chinese children 3-5 years old. AB - A total of 1344 children, 3-5 yr old, from two rural counties, Haidian and Miyun, close to Beijing, China, were examined in 1992. A modified DDE Index was employed in this study, and a pre-designed formula was used to calculate an enamel defect score (EDS) for each individual in the study. Oral examination was performed by one dentist under natural light using a standard mouth mirror and dental probe. Developmental enamel lesions were diagnosed without drying or cleaning the teeth prior to examination. Results from this study showed that primary teeth with defective enamel were seen in 23.9% of the children examined, opacity in 1.6%, and hypoplasia in 22.2%. Among the teeth, maxillary central and lateral incisors were affected by enamel hypoplasia most often (40.8% and 39.2%), followed by maxillary canines (25.7%), maxillary 1st molars (22.1%), and mandibular 1st molars (18.5%). The enamel defects occurred more frequently on the buccal surfaces of teeth than on any other surface. The study did not find a significant association of the children's age, family socioeconomic status, and anthropometric measurements with the distribution of enamel defects. However, there was a significantly higher prevalence of teeth with defects in males compared to females (P < 0.001), as well as mean tooth surfaces with defects (P < 0.05), and mean EDS (P < 0.05). Children born prematurely were shown to have four times more enamel lesions than children who were full term (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781304 TI - Evaluation of aesthetics for the different classifications of the Tooth Surface Index of Fluorosis. AB - The prevalence of dental fluorosis for children both from fluoridated and non fluoridated communities has increased dramatically in some regions of North America. This study evaluated the aesthetics of dental fluorosis for school-aged children from a reference population of 1131 children. The methodology from the Social Acceptability Scale of Occlusal Conditions (SASOC), part of the Dental Aesthetics Index (DAI), was used to assess fluorosis-related aesthetics. Pairs of semantic differentiated adjectives adapted from SASOC were used to rate fifty 35 mm slides of anterior teeth. Sampling of children from the different categories of the Tooth Surface Index of Fluorosis (TSIF) on anterior permanent teeth was weighted to permit sufficient numbers of slides for the different classifications of the TSIF. Each slide was presented to a stratified random sample of pairs of parents and children who were participants in the original study. A convenience sample of dental professionals was also included. Analysis compared different classifications of "affected" slides (non-zero TSIF scores), with the mean aesthetic score computed from all "non-affected" slides (TSIF = 0). Results from children, parents, and professionals showed that there were highly significant differences between ratings of low and high TSIF scores. The only non-significant differences were between TSIF 4 and TSIF 5 & 6, which all three groups did not distinguish, as well as TSIF 1 versus TSIF 2 & 3, which children could not distinguish. PMID- 7781305 TI - Evaluation of screening for oral cancer and precancer in a company headquarters. AB - Oral cancer and precancer appear to fulfil many of the criteria for a disease suitable for mass screening. Several commercial organisations in the UK have introduced screening for their employees. One program has been formally evaluated over the course of 1 yr. Of 553 company headquarters staff aged > or = 40 yr, 292 (53%) responded to the well-publicised screening invitation and received a simple clinical examination of the oral mucosa from one of two company dentists. In addition, 17 staff were screened from a separate company work-site. After screening, subjects were examined independently by an oral medicine specialist with access to the relevant diagnostic aids. The dentists' screening decisions were validated against the specialist's definitive diagnoses (the 'gold standard'). The true prevalence of subjects with lesions diagnosed as positive (white patch, red patch or ulcer of greater than 2 weeks' duration) was 17 (5.5%). Overall, sensitivity was 0.71 and specificity, 0.99. The compliance rate to screening among headquarters subjects in seven occupational categories did not differ significantly from the occupational profile for all headquarters personnel. Estimates of relative risk of a positive diagnosis were calculated by logistic regression for five independent variables; gender, age, moderate smoking, heavy smoking, and smoking combined with greater than low risk alcohol consumption. Only heavy smoking (> or = 20 cigarettes per day) produced a significant odds ratio (3.43, P < 0.05). PMID- 7781306 TI - Opinions of different subgroups of dentists and patients about the ideal dentist and the ideal patient. AB - The aim was to study whether subgroups of lay people and dentists differ in their opinions about the ideal dentist and the ideal patient. This was done by analyzing further a data set containing responses on single statements regarding different aspects of dentist-patient relationship that have been reported previously. A questionnaire containing 124 five-class Likert scale statements and questions about the background of the respondents was sent in November 1988 to a representative sample of lay people and to all dentists in Kuopio and North Karelia Provinces in Finland. To extract areas of interdependence for both dentists and patients, factor analyses were applied to the data and factor scores were calculated for further analyses. Differences in the opinions were studied between dentists and patients as well as among subgroups of patients and dentists. The power of the selected factors in discriminating between dentists and patients, and different subgroups of dentists and patients was evaluated by means of logistic regression analyses. The expectations of dentists and patients were similar about the ideal patient. About the ideal dentist, dentists and patients agreed only on one of the five factors, i.e. communicativeness and informativeness. Differences, especially in the opinions about the ideal patient, were found between following subgroups of patients: non-regular and regular attenders, males and females, old and young, patients with low and high education and different occupational status; and between private practitioners and community dentists. PMID- 7781307 TI - Utilization of dental services in refugees in Sweden 1975-1985. AB - Prior to 1940 the population of Sweden was one of the most homogeneous in Europe, with only 0.5% foreign born. Fifty years later, in 1990, the proportion of immigrants was around 15%. In order to describe and analyze consumption of dental care in different refugee groups in Sweden, data registered by the Department of Immigration and the National Social Insurance Board, on a random sample of 2489 refugees arriving in Sweden 1975-85, were merged. Information on nationality, date of arrival in Sweden, date of granting of permanent resident status and statistics on consumption of dental care were retrieved. During the period studied a total of 50,521 refugees arrived in Sweden. The average interval between arrival in Sweden and the first dental visit was 4.5 yr (95% < 1: 4.2 4.7). The total treatment time during the first course of treatment was 165.5 min (95% < 1: 148.7-182.3). Consumption of dental care did not decrease with an increased number of treatments. Only 38% of the refugees had visited a dentist at all in Sweden. With increasing number of years in Sweden the number of courses of dental treatment increased, but 41% of the refugees who had visited the dentist in Sweden had done so only once. This study shows a low utilization of dental services among refugees in Sweden in general. Refugees with dental visits in Sweden, in particular, had a high dental consumption. PMID- 7781308 TI - Patterns of spatial functioning in Turner's syndrome. AB - This paper presents results from a study of task performance on a variety of spatial tasks in 9-11 year-old children with Turner's Syndrome (T.S.), divided into those with genotype 45XO and those with Mixed genotypes, including isochromosomes of X and mosaicism. There was a significant overall effect of group reflecting impaired spatial cognition in T.S. with greater decrement in the 45XO group. Further investigation of the significant group by task interaction indicated that the group effects appeared on a visuo-perceptual task and on three visuo-constructional tasks but that there were no specific deficits in the T.S. groups on visuo-spatial or tactile-spatial tasks. In T.S., visuo-perceptual and visuo-constructive sub-systems of spatial skill may be more vulnerable than other components of spatial cognition, to the neuro-biological influences which contribute to the disorder. Such dissociation supports theories of modularity in the development of spatial skill. The spatial tasks which create difficulty overlap only partially with those for which there are sex differences amongst normal children and do not represent a simple exaggeration of normal male-female differences. PMID- 7781309 TI - Disorders of auditory identification in dementia of the Alzheimer type. AB - Fifteen patients with probable DAT and 18 matched controls were given tests that required the identification of verbal (phonemes and words) and non verbal (sounds and melodies) stimuli. In all tests, DAT patients made significantly more errors than controls. Errors predominated in non verbal tests in both groups. DAT patients (and, to a lesser degree, control subjects) made almost exclusively acoustic errors in word-identification, while errors in the identification of sounds and melodies could be either semantic or acoustic. Some categories of errors were observed predominantly in DAT patients. These results suggest that, in addition to their cognitive impairment, DAT patients have a specific deficiency of central auditory perception. PMID- 7781310 TI - Understanding impaired analysis of faces by patients with probable Alzheimer's disease. AB - The purpose of this study was to analyze the facial recognition skills of patients diagnosed with Probable Alzheimer's Disease (AD). The performance of 181 AD patients was evaluated to address their ability to: analyze visual forms, to discriminate individual faces, and to recognize and name familiar famous faces. The results of the study demonstrate that the ability to analyze visual information is more vulnerable early in dementia than is the ability to discriminate individual faces. The inability to recognize familiar faces among the AD patients was related to impairments of their lexical/semantic system, rather than to a specific defect in facial discrimination. These data are fully consistent with existing models of face processing and recognition, and suggest that the recognition defect in AD is related to the naming component of face recognition, rather than the perceptual component. PMID- 7781311 TI - Impaired arithmetic facts but intact conceptual knowledge--a single-case study of dyscalculia. AB - We present the case of a young, highly educated patient who showed severe problems in basic arithmetic after a bone marrow transplant followed by extensive irradiation and chemotherapy. Despite his inability to resolve arithmetical fact problems (as 2 + 3), he showed intact processing of algebraic expressions and excellent understanding of complex arithmetic text problems. He perfectly knew arithmetic principles and applied them in various tasks. The performance of the patient suggests that conceptual knowledge (in addition to arithmetical fact knowledge and arithmetic procedures) is a functionally independent component of the calculation system. PMID- 7781312 TI - Psychoacoustical deficits related to bilateral subcortical hemorrhages. A case with apperceptive auditory agnosia. AB - We report a case of acute deafness secondary to bilateral hemorrhages involving the external capsule and extending to both temporal isthmi. The lesions probably disrupted both auditory radiations. Deafness disappeared within 2 weeks leading to a transient auditory agnosia for environmental and verbal sounds. Performance on audiological and neurolinguistic tests were consistent with the hypothesis of a deficit of non-specific auditory processes. Psychoacoustical deficits related to subcortical lesions are very rare and might differ from those due to cortical lesions by the lack of aphasia. The present case and both previous cases with subcortical lesions might suffer from auditory agnosia of apperceptive type. Its characteristics and the role of non-specific auditory processes are discussed using the data obtained from this third case. PMID- 7781313 TI - Selective deficit in processing double letters. AB - This paper reports a patient with a selective difficulty in spelling words and pseudowords with geminate (double) consonants. In all writing tasks, deletions of a geminate consonant occurred ten times more often than deletions of a consonant in a non-geminate cluster. In addition, the probability of substituting both geminate consonants was indistinguishable from the probability of substituting one consonant in a non-geminate cluster; and, the probability of substituting only one geminate consonant was close to zero, and significantly lower than the probability of substituting one consonant in a non-geminate cluster. This pattern of performance is consistent with the hypothesis that grapheme quantity and identity are separately represented in orthographic representations. The fact that these errors occurred in the absence of a significant number of geminate transpositions is interpreted as support for the hypothesis that letter gemination is specified by a "doubling feature." PMID- 7781315 TI - Reduplication of an event after head injury? A cautionary case report. AB - We report the case of a 69 year-old man who suffered head trauma in a road traffic accident. Subsequently, there was personality change, memory-impairment and the persisting 'delusion' that he had been involved in an earlier car accident. On the basis of detailed interviews with the patient (and his wife), we provide an explicit account of how the content of his reduplicative paramnesia could have arisen. We are concerned to stress that the patient's 'delusion' is a belief held on reasonable grounds. PMID- 7781314 TI - Unilateral somatoparaphrenia after right hemisphere stroke: a case description. AB - We report a case of somatoparaphrenia in a 41 year-old man after right temporo parietal stroke. An elaborate system of delusional beliefs was observed concerning the initially paralysed left leg, arm, and hand. The course of these beliefs is analysed as the patient progresses from a full-blown delusional state to having excellent insight into his condition. We outline the types of explantation that seem required to understand how somatoparaphrenic beliefs can arise. PMID- 7781316 TI - Personal name anomia: a single case study. AB - A case presenting an anomia specific for person proper names but no naming impairment either for other types of proper names or for common names is reported. The deficit was equally present both in face-naming and in naming upon definition and was not affected by the descriptiveness of the labels borne by the individuals. The patient had no semantic processing impairment either for faces or names. The results are discussed in terms of impaired access to intact phonological representations. PMID- 7781317 TI - The influence of neglected stimuli on free drawing in a patient with hemi inattention. AB - A patient with severe left hemi-inattention was found to be influenced by neglected stimuli in free drawing tasks. He was presented 64 sheets of paper: 32 had geometric figures on the left side and 32 on the right side. The patient was asked what he saw and invited to draw a subject of his choice on the sheet of paper. The patient always denied seeing anything when the figures were on the left side, while he identified the figures on the right side. Four judges examined the patient's drawings and all of them agreed that 11 drawings were influenced by neglected stimuli and none by non-neglected ones. The drawings he made were similar but not the exact reproduction of neglected figures. This finding confirms that visual processing can proceed without awareness in a patient with hemi-inattention. PMID- 7781318 TI - Odor recognition memory is better under bilateral than unilateral test conditions. AB - Two odor memory tests were administered unilaterally (left and right) and bilaterally to the same set of 24 men and 24 women on two test occasions. These tests were (i) a "multiple-target" test (MTT) in which three target stimuli were selected, after 10-, 30-, and 60-sec retention intervals, from stimulus sets containing both target and distracter stimuli, and (ii) a 9-item "single-target" three-choice test (STT), in which single stimuli were selected from stimuli sets containing two distracters. Overall, odor memory scores were higher under bilateral than unilateral testing, and higher on the second than on the first test session. Unilateral testing resulted in a monotonic delay-related forgetting function. No differences were observed in the odor memory test scores of the left and right sides of the nose, and no significant correlations were present between these scores and scores on a battery non-olfactory memory tests. On the STT, the female, but not the male, subjects demonstrated better performance on the second, than on the first, test session. The results of this study imply that odor memory is facilitated centrally by bilateral activation, and that a memory system may exist for odors which is distinct from other memory systems. PMID- 7781319 TI - Familial sinistrality: the utility of calculating exact genotype probabilities for individuals. AB - Measures of familial sinistrality are frequently used in neuropsychological research. However they suffer from the problem that they are essentially a global measure of phenotypes in the family, whereas they are interpreted as an indicator of the genotype of the individual concerned. In this paper it is shown how to calculate a precise probabilistic estimate of a proband's genotype, given a particular genetic model of handedness, using all of the information available in a family tree. Example calculations are provided for a range of families with one or two sinistral relatives. Genotype probabilities are also calculated for a large population data set (the National Childhood Encephalopathy Study) and it is shown that familial sinistrality does not account for all of the variability present in the genotype probabilities, and that genotype probabilities provide an additional prediction of individual sinistrality after taking familial sinistrality into account, whereas all of the information in familial sinistrality is accounted for by the genotype probabilities. Finally it is shown how genotype probabilities can be used to assess whether there is heterozygote advantage for a characteristic, and using this method it is suggested that there is no support for heterozygotes having higher intellectual ability than homozygotes. PMID- 7781320 TI - A selective impairment of hand posture for object utilization in apraxia. AB - This study reports the case of an apraxic patient who was impaired in all aspects of gestural behavior following bilateral posterior parietal cortex lesions. The main impairment concerned manual prehension of objects during their utilization. The deficit contrasted with both normal movement trajectories of the arm during execution of such gestures, and with accurate manual prehension in the context of simple reaching movements. Although recognition of gestures and pantomimes made by the examiner was preserved, the patient showed a striking inability to visually discriminate or describe manual prehension associated with object utilization. We thus propose the existence of specialized cortical mechanisms for the representation and activation of the postural schemata of the hand required for complex actions. PMID- 7781321 TI - Evidence for the independence of recognition and recency memory in amnesic subjects. AB - The present study examined two groups of amnesic subjects (Korsakoff and Post Encephalitic) on tests of object recency. In the first test the subject tried to select the object that had been shown most recently from a pair of familiar objects. Compared with their respective controls both amnesic group were severely, and similarly, impaired. This impairment did not, however, appear to reflect a failure to engage specific rehearsal strategies. In the second test a dissociation was found between judgements of recency and recognition for the same item. This was consistent with the lack of correlation between recency performance and performance on a number of other memory tests. The present findings suggest that the underlying cause of the recency memory deficit in amnesia is different to that responsible for other memory losses. They also point to a dissociation between the processes involved in estimating recency and temporal duration. PMID- 7781322 TI - Task interruption in prospective memory: a frontal lobe function? AB - Prospective memory involves remembering an intention to do something as well as remembering the content of the task. It also shares common features with executive skills that are argued to be mediated by the frontal lobes. This paper describes performance on tests of prospective memory by a subject with bilateral frontal lobe infarcts and good retrospective memory but who displayed impairments of planning, initiation and inhibition of ongoing behaviour. The results lend some support to the suggestion that separate neuroanatomical pathways underly retrospective and prospective memory. They also indicate dissociable features within prospective memory that may reflect differences in utilisation of attentional resources and inhibitory control mechanisms. PMID- 7781323 TI - Activation of human hippocampal formation during memory for faces: a PET study. AB - Using positron emission tomography, we examined cerebral blood flow changes in human subjects whilst engaged in the visual processing of face stimuli. A task requiring anterograde memory of faces was compared with a control task involving simple gender classification--considered an automatic process that did not require any significant memory component. A second task requiring recognition of famous politicians' faces, and therefore involving long-term "semantic" memory, was also contrasted with the control task. To identify brain regions associated with primary visual processing of the face we compared all tasks against a control population scanned with eyes closed. Our results indicate--(1) The involvement of bilateral lingual/fusiform gyri and the right parahippocampal gyrus in addition to striate cortex in primary visual processing of the face; (2) the involvement of the left hippocampal gyrus in both types of memory; (3) a relative decrease in local cerebral blood flow in the inferior parietal lobules in long-term "semantic" memory. In addition, both memory tasks resulted in a suppression of cerebral blood flow in the left superior temporal cortex. We conclude that right hippocampal regions are involved in a largely automatic, primary processing of faces, while left hippocampal regions are additionally involved when explicit memory for faces is required. PMID- 7781324 TI - Adenine nucleotide depletion in cryopreserved human cardiac valves: the "stunned" leaflet interstitial cell population. AB - Preparation protocols for human cardiac valves are intended to minimize cytotoxicity because it has been thought that viable leaflet interstitial cells may enhance homograft durability. Preimplantation factors influencing the status of these cells at the time of transplantation include ischemia, disinfection, and cryopreservation freezing programs. In these experiments, adenine nucleotide quantitation was undertaken to assess metabolic consequences of preparation; preharvest ischemia served as an independent variable to examine the relationship between time of procurement (postmortem) and high-energy phosphate status of the cryopreserved leaflets at thaw. Nucleotides were measured using high-performance liquid chromatography performed on extracts of semilunar cusps from 25 cryopreserved human valves with documented ischemic times. Results indicate total adenine nucleotides (TAN; [ATP] + [ADP] + [AMP], in nmol TAN/mg leaflet protein) are higher (P < 0.05) after < 2 h of harvest ischemia (1.16 +/- 0.36) than with ischemic times of 3-6 h (undetected), 7-12 h (0.18 +/- 0.07), and 13-20 h (0.06 +/- 0.06). Depletion of ATP was similar, with many leaflets devoid of detectable levels. Net utilization of leaflet energy stores demonstrates time dependency when assayed after completed processing. However, relatively elevated catabolites, even with brief ischemia, and infrequently identified ATP, ADP, and AMP, suggest a consumption so accelerated that the following cryopreservation it is virtually independent of procurement-associated ischemia. We conclude resumption of a functional cell population obligates significant de novo phosphoanhydride boned reformation or a repopulation of dead/dying interstitial cells from a subset surviving the apparently severe rigors of valve preparation. PMID- 7781325 TI - Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man. AB - Hepatic cryotherapy is a relatively new technique used to treat both primary and secondary tumors. This paper concerns the changes in serum aspartate transaminase (AST) in 45 patients following both single and double freeze with partial thaw cycles. There was considerable elevation in serum AST, greatest on the day of operation, and there was a significantly higher peak AST following the double freeze cycles (1159; SE, 117.5) compared with single-freeze/thaw procedures (437; SE, 61.7). This finding indicates greater hepatocellular disruption which may be important both in planning clinical hepatic cryosurgery to achieve adequate destruction and also to avoid the morbidity of the cryoshock phenomenon. PMID- 7781327 TI - Membrane fluidity as a factor in production and stability of bacterial ice nuclei active at high subfreezing temperatures. AB - Detailed measurements were made of the rate of appearance of bacterial ice nuclei upon cooling of suspensions of Pseudomonas syringae cells and the disappearance of ice nuclei upon warming of the cells before assay for ice nucleation activity. While no substantial change in numbers of ice nuclei active at either -5 or at -9 degrees C was observed in cells that were grown at temperatures lower than 24 degrees C and cooled to 21 degrees C before assay, large increases in -5 but not 9 degrees C ice nuclei were observed in cells grown at temperatures greater than 24 degrees C. Ice nucleation activity of cells subjected to a decrease in temperature before assay increased immediately upon temperature shift, but 8 to 12 min was required before maximum rates of increase in numbers of ice nuclei were observed. The rate of appearance of ice nuclei in cell suspensions incubated at relatively cold temperatures prior to assay was substantially less than those incubated at temperatures approaching 24 degrees C. Cells rapidly lost ice nucleation activity when warmed to above 27 degrees C before assay; the rate of loss of ice nuclei in cells grown at a given temperature increased rapidly as the temperature to which they were warmed before assay increased. Ice nuclei disappeared most rapidly when cells grown at low temperatures were warmed before assay, suggesting that ice nucleus stability was lower in highly fluid membranes. The logarithm of the half-life of ice nuclei in cells was directly related to the concentration of the membrane fluidizing agent, 2-phenethyl alcohol, in which they were suspended. PMID- 7781326 TI - The temperature dependence in the hydraulic conductivity, Lp, of the mouse sperm plasma membrane shows a discontinuity between 4 and 0 degrees C. AB - Cryopreservation of sperm from transgenic mice would make possible the economical perpetuation of these genetic models. In order to design a protocol for this process, it was first necessary to determine the hydraulic conductivity, Lp, or water permeability, of the plasma membrane as a function of temperature to calculate its activation energy, Ea. This was done with sperm from the caudae epididymides of CD-1 mice, using the hyposmotic cell lysis method, in which the critical osmolality, Osmcrit, defined as the osmolality at which 50% of the cells lyse, was first determined, and then the time, t, to lysis of 50% of the cells in a medium of Osm < Osmcrit was obtained. Values (mean +/- SEM, n = 10) of Osmcrit at 37, 22, 4, and 0 degrees C were 32.1 +/- 2.7, 33.7 +/- 4.1, 30.8 +/- 3.4, and 101.0 +/- 10.8 mOsm, and of t in 17 mOsm medium were 40.6 +/- 2.4, 33.8 +/- 5.7, 25.0 +/- 4.4, and 4.7 +/- 1.2 s, respectively. Values of Lp were calculated from Osmcrit and t by two different algorithms, one based on the high-amplitude swelling model used with sperm from other mammalian species and the other based on a low-amplitude swelling model. Values of Lp in micron.min-1.atm-1 from the high-amplitude swelling model at 37, 22, 4, and 0 degrees C were 1.41 +/- 0.08, 1.88 +/- 0.35, 2.12 +/- 0.19, and 1.13 +/- 0.1, respectively. From the low amplitude swelling model, the Lp values were 0.025 +/- 0.001, 0.040 +/- 0.008, 0.082 +/- 0.029, and 1.66 +/- 0.23. Examination of mouse sperm in hyposmotic media by microscopy revealed little swelling of the cells, indicating that the low-amplitude swelling model may be the one more applicable to these cells. The temperature dependence, and hence Ea, of Lp shows a marked discontinuity between 4 and 0 degrees C with values calculated from either model. This suggests a membrane phase transition to a more brittle structure in this temperature range, consistent with the observed marked increase in Osmcrit (P < 0.0003) and decrease in t (P < 0.0001) at 0 degrees C compared to the other temperatures. In the presence of 1 M glycerol, there was no discontinuity between 4 and 0 degrees C in the values of Osmcrit, consistent with the ability of glycerol to fluidize the membrane. Low hydraulic conductivity and low-temperature embrittlement of the plasma membrane are proposed as two factors leading to mouse sperm hypersensitivity to cryodamage. PMID- 7781328 TI - Regulation of internal Ca2+ by chilled bull and boar spermatozoa. AB - Intracellular Ca2+ in ejaculated spermatozoa from five bulls and five boars was determined with indo-1,AM in Ca(2+)-free medium. Aliquots of each ejaculate were then wrapped and held either on ice or at 25 degrees C for 20 min. At this time all samples were returned to 25 degrees C, either Ca(2+)-free medium or medium containing 1 mM Ca2+ was added, and intracellular Ca2+ was determined for an additional 120 min. Before and immediately after chilling, internal Ca2+ in bull spermatozoa did not differ. However, exogenous Ca2+ caused both control and chilled bovine spermatozoa to accumulate Ca2+ over the subsequent 120 min (P < 0.01) with the control spermatozoal rate of Ca2+ intake being faster than that of the chilled (slopes, 29.531 vs 8.374 relative Ca2+ units/min; least squares means (lsmean) x 10(4) +/- 1.901 (pooled SE); P < 0.01). Viability of all spermatozoa was reduced after Ca2+ exposure, and the acrosomal morphology of chilled cells was adversely affected by Ca2+. For boar spermatozoa, chilling caused an immediate increase in internal Ca2+, confirming the greater sensitivity of boar spermatozoa to low temperatures. The presence of exogenous Ca2+ caused greater Ca2+ uptake by both control and chilled porcine cells relative to their Ca(2+) free analogues (0.939 vs 0.764 and 1.015 vs 0.836 Ca2+ units; lsmean +/- 0.166 (pooled SE); P < 0.01 for control and chilled boar spermatozoa with and without Ca2+ at 150 min). Control spermatozoa, however, accumulated Ca2+ (P < 0.01) at a much greater rate (slope, 20.964 +/- 2.73 relative Ca2+ units x 10(4)/min; P < or = 0.001) than chilled cells, which only tended (P = 0.08) to accumulate Ca2+ (slope, 4.782 +/- 2.73 relative Ca2+ units x 10(4)/min). This study suggest that chilling causes a species-specific effect on Ca2+ regulatory capabilities of spermatozoa that differs from cold shock and that spermatozoa may be able to compensate, at least partially, for such injuries. PMID- 7781330 TI - Is there room for the heart in CHEST? PMID- 7781329 TI - Fracture phenomena in an isotonic salt solution during freezing and their elimination using glycerol. AB - Thermal stress and consequent fracture in frozen organs or cell suspensions have been proposed to be two causes of cell cryoinjury. A specific device was developed to study the thermal stress and the fracture phenomena during a slow cooling process of isotonic NaCl solutions with different concentrations of glycerol (cryoprotectant) in a cylindrical tube. It was shown from the experimental results that glycerol significantly influenced the solidification process of the ternary solutions and reduced the thermal stress. The higher the initial glycerol concentration, the lower the thermal stress in the frozen solutions. Glycerol concentrations over 0.3 M were sufficient to eliminate the fracture of the frozen solutions under the present experimental conditions. To explain the action of glycerol in reducing the thermal stress and preventing the ice fracture, a further study on ice crystal formation and growth of ice in these solutions was undertaken using cryomicroscopy. It is known from previous studies that an increase of initial glycerol concentration reduced frozen fraction of water in the solution at any given low temperature due to colligative properties of solution, which reduced the total ice volume expansion during water solidification. The present cryomicroscopic investigation showed that under a fixed cooling condition the different initial glycerol concentrations induced the different microstructures of the frozen solutions at not only a given low temperature but also a given frozen fraction of water. It has been known that ice volume expansion during solidification is a major factor causing the thermal stress and the interior microstructure is critical for the mechanical strength of a solid. Therefore, functions of glycerol in reducing the total ice volume expansion during water solidification and in influencing interior microstructure of the ice may contribute to reduce the thermal stress and prevent the fracture in the frozen solutions. PMID- 7781331 TI - ICU scoring and clinical decision making. PMID- 7781332 TI - The disruptive ICU. An issue to lose sleep over? PMID- 7781333 TI - Should pulmonary metastases be resected? PMID- 7781334 TI - Pulmonary tuberculosis and steroids. PMID- 7781335 TI - Partial or total direct pulmonary venous drainage to right atrium due to malposition of septum primum. Anatomic and echocardiographic findings and surgical treatment: a study based on 36 cases. AB - The clinical and anatomic findings in 36 patients (21 postmortem cases and 15 living patients) with partially anomalous (16 [44%]) or totally anomalous (20 [56%]) pulmonary venous drainage directly to the right atrium constitute the material basis of this report. Displacement of septum primum--leftward in atrial situs solitus or rightward in atrial situs inversus--was present in all and appeared responsible for the anomalous pulmonary venous drainage. The pulmonary veins were connected with what normally constitutes the posterior wall of the left atrium, which became incorporated into the right atrium because of atrial septal displacement. This abnormality occurred predominantly in patients with visceral heterotaxy, usually with polysplenia, or rarely with asplenia or a normally formed spleen. Poor development or absence of septum secundum appeared responsible for the malposition of septum primum. Echocardiographic recognition of the displacement of septum primum facilitated surgical management. PMID- 7781336 TI - Neurohormonal activation and exercise function in patients with severe heart failure and patients with left ventricular assist system. A comparative study. AB - OBJECTIVES: The aim of this study was to evaluate the effects of implantation of a left ventricular assist system (LVAS) on the neurohormonal status, exercise capacity and symptomatic state in patients with severe congestive heart failure (CHF). BACKGROUND: Severe CHF is characterized by decreased exercise tolerance and activation of several neurohormonal systems. METHODS: Parameters of neurohormonal activation and exercise capacity in patients with LVAS (n = 7) were compared with those in groups of New York Heart Association (NYHA) class 3 (n = 121) and class 4 (n = 81) patients. Plasma levels of norepinephrine (NE), plasma renin activity (PRA), and atrial natriuretic peptide (ANP) and maximal and submaximal exercise capacities were measured monthly in LVAS patients and compared with results in CHF patients. RESULTS: Plasma NE and PRA levels were significantly lower in LVAS patients than in NYHA class 4 patients, and plasma ANP levels in LVAS patients were significantly lower than those in NYHA class 3 and 4 patients. The distance walked during submaximal exercise testing and peak oxygen consumption during maximal exercise testing were similar for the LVAS and NYHA class 3 patients. The class 4 patients were unable to exercise. CONCLUSIONS: We conclude that the LVAS lessens the neurohormonal activation and exercise intolerance characteristic of the CHF state and that the exercise capacity early after LVAS (< 4 months) is similar to that observed in NYHA class 3 patients. PMID- 7781337 TI - The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study. AB - STUDY OBJECTIVE: Patent foramen ovale (PFO) is present in 10 to 35% of people and has been reported to be an important risk factor for cardioembolic cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs), especially in younger patients. While contrast transthoracic echocardiography has been used to detect PFO, contrast transesophageal echocardiography (TEE) has a greater sensitivity. Prior studies reported the incidence of PFO in patients presenting with a CVA or TIA. DESIGN: To determine the incidence of PFO in a more general population, we reviewed 1,000 consecutive TEEs performed with contrast and color Doppler for the presence of PFO and other cardioembolic risk factors, including atrial septal aneurysm (ASA), aortic plaque, atrial fibrillation (AFib), and atrial thrombi. While imaging with monoplane or biplane TEE, multiple injections of agitated saline solution were injected during cough or Valsalva maneuver to detect flow through a PFO. PATIENTS: There were 482 male and 518 female patients with mean age of 60 +/- 17 years (range 11 to 93 years). RESULTS: Patent foramen ovale was found in 9.2% of all patients and, though seen in all age groups divided by decade, the incidence in patients aged 40 to 49 years was greater than those aged 70 to 79 years (12.96% vs 6.15%, p = 0.03). Contrast TEE had a much higher detection rate than color Doppler alone. Importantly, there was no greater incidence of PFO in patients with CVA vs those without CVA, or in male vs female patients. Also, there was a very strong correlation between the presence of ASA and PFO (p < .001). CONCLUSION: Thus, PFO detected by TEE, frequently seen with ASA, is seen in all age groups and does not in itself present a risk factor for CVA. The association of PFO with peripheral thrombosis and CVA needs further study. PMID- 7781338 TI - Right ventricular function in patients with severe COPD evaluated for lung transplantation. Lung Transplant Group. AB - Right ventricular function was measured in ten patients with severe COPD (mean FEV1 = 0.48 +/- 0.2 L/s) as part of an evaluation for single lung transplant (SLT). Right ventricular ejection fraction (RVEF) was determined by two methods: first-pass radionuclide scan by multigated acquisition (MUGA) and by using a fast thermistor tipped RVEF/volumetric pulmonary artery catheter. None of the patients had clinical evidence of active right heart failure, although mild resting pulmonary hypertension (mean pulmonary artery pressure [PAP] = 24 +/- 4 mm Hg) that worsened with minimal exercise (mean PAP = 39 +/- 11 mm Hg) was present. There was a significant difference in RVEF measured by the two methods (mean MUGA RVEF = 57 +/- 10%, mean catheter RVEF = 27 +/- 8%; p < 0.00005). RVEF determined by both methods was correlated with hemodynamic and gas exchange variables obtained during rest and at maximal exercise. There were significant, yet inverse, correlations between RVEF measured by catheter and cardiac index measured during exercise (CIex), as well as with exercise pulmonary vascular resistance index (PVRI). There were no significant correlations found between MUGA RVEF and any gas exchange or hemodynamic variables. Significant correlations were found with the catheter-measured right ventricular end-diastolic volume (RVEDV) and CIex (r = 0.9 p < 0.005), with maximal oxygen consumption during exercise (VO2max) (r = 0.86 p < 0.0025), with exercise stroke volume index (SVI) (r = 0.76 p < 0.01), and exercise central venous pressure (CVP) (r = 0.62 p < 0.05). Echocardiographic studies revealed right ventricular dilatation and mild tricuspid regurgitation (TR) in all patients. The strong correlation between RVEDV, CIex, and VO2max supports the concept that in these patients, as long as there is no clinical evidence of right heart failure (resting CVP still within normal limits), those with the largest RVEDVs use the Frank Starling principle to their best advantage to remain more functional.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7781339 TI - Effect of acute allograft rejection on exercise hemodynamics in patients who have undergone cardiac transplantation. AB - The effect of acute allograft rejection on exercise hemodynamics was evaluated in 8 consecutive cardiac allograft recipients (group 1) when the right ventricular endomyocardial biopsy showed evidence of allograft rejection (R), and when no evidence of rejection (NR) was present. A separate group of 10 cardiac transplant recipients (group 2) with no evidence of rejection on biopsy done at the end of the first and second year post-transplantation served as controls. The exercise hemodynamics were abnormal in both groups in both studies with a moderate increase of the pulmonary artery wedge pressure to a mean of 17.2 (NR) and 19.4 mm Hg (R) in group 1 (p = not significant [NS]) and 20.1 and 21.2 mm Hg in group 2 (p = NS), a mild increase of the mean right atrial pressure to a mean of 10 mm Hg (NR) and 10 mm Hg (R) in group 1 (p = NS), 11.9 mm Hg and 12.5 mm Hg in group 2 (p = NS), and a moderate increase of the arteriovenous oxygen content difference to a mean of 8.5 (NR) and 8.4 vol percent (R) in group 1 and 8.3 and 8.0 vol percent in group 2. No significant difference was observed between the two studies of the same group in any of the hemodynamic parameters except for the heart rate in group 1 (from 91 +/- 16 to 97 +/- 16 beats/min [p < 0.05] with and without evidence of allograft rejection, respectively). In conclusion, heart transplant recipients do not usually manifest further exercise hemodynamic deterioration during mild to moderate rejection. PMID- 7781340 TI - The role of the 'pericardial window' in AIDS. AB - BACKGROUND: The leading cause of pericardial effusion in urban hospitals is now AIDS-related pathologies. Clinically, these effusions are a diagnostic and management dilemma. In our institution, pericardial biopsy and operative drainage have become part of the diagnostic and management plan. Surgical intervention, however, has appeared to have little clinical impact. METHODS: A retrospective review was conducted of all patients (n = 29) diagnosed as having AIDS who underwent "pericardial window" for pericardial effusions from 1986 to 1994. RESULTS: Fluid cultures and pericardial biopsy were performed in all cases. Twenty-four percent of culture or biopsy specimens were diagnostic (7 of 29 = 2 adenocarcinoma, 3 lymphoma, 1 Staphylococcus aureus, 1 Mycobacterium tuberculosis). In 94% of cases, there was no change in clinical management based on operative results. In 4 of 7 cases, the patients were ineligible for the indicated therapy based on underlying illness and in 1 of 7, the patient was receiving appropriate therapy for previously diagnosed disease. Ventilatory complications were noted in 17%. Three patients did not wean from the ventilator and died shortly after the operation. Sixty-nine percent mortality was noted at 8 weeks post-operatively. One hundred percent mortality was noted at 22 weeks with 86% follow-up. CONCLUSION: AIDS-related pericardial effusion is associated with a grave prognosis. Operations for diagnostic benefit provide little practical information and are not justified. PMID- 7781341 TI - Pulmonary resection for metastases of colorectal origin. AB - STUDY OBJECTIVE: To develop selection criteria for pulmonary metastasectomy in patients with metastases of colorectal cancer confined to the lungs. DESIGN: A retrospective study. SETTING: Medical records of all patients operated on for this condition in the Netherlands in the period 1982 to 1992 (n = 38). INTERVENTION: Evaluation by means of Cox's proportional hazards regression analysis of factors, which might relate to postthoracotomy disease-free survival and/or postthoracotomy survival. MEASUREMENTS AND RESULTS: The 5-year disease free survival was 31%, and the overall 5-year survival was 43% (Kaplan-Meyer). Multivariately, a number of three or fewer metastases (p = 0.012) and a short delay between detection of pulmonary metastases and resection (p = 0.05) related to a longer postthoracotomy disease-free interval. A longer interval between resection of the primary tumor and detection of lung metastases related to a longer postthoracotomy survival (p = 0.021). CONCLUSIONS: Patients with three or less pulmonary metastases of colorectal origin may benefit from resection; once metastases have been detected, resection should not be postponed. PMID- 7781342 TI - Empyema thoracis. Therapeutic management and outcome. AB - STUDY OBJECTIVE: We evaluated treatment and outcome of patients with thoracic empyema at a teaching institution. DESIGN AND SETTING: Retrospective chart review over a 44-month period at a university hospital. PATIENTS AND MEASUREMENTS: Charts of patients with a hospital discharge diagnosis of thoracic empyema were reviewed. Age, symptoms, alcohol use, empyema etiology, culture results, number of loculations, date and success of each procedure, length of hospital stay, and hospital discharge status were recorded for each patient. Success of procedure, recovery time, time between procedures, and total hospitalization time were compared between procedures and between subgroups. RESULTS: Charts from 43 patients were reviewed. Twenty-four of 43 (56%) cases were parapneumonic empyemas. Forty of 43 (93%) patients had symptoms attributable to their empyema, with fever being the most common (65%). Seventy-nine procedures were needed to treat the 43 patients (1.84 procedures per patient). Success rates ranged from 11% (3/27) for tube thoracostomy to 95% (21/22) for decortication (p = 0.0001). Delay between procedures averaged 6.2 +/- 1.1 (mean +/- SEM) days between the first and second procedure (n = 27), and 10.4 +/- 5.1 days between the second and third procedure (n = 8). Mean recovery after successful intervention ranged from 9 to 19.3 days depending on the procedure (p = NS). Comparisons between multiloculated and uniloculated empyemas, parapneumonic and nonparapneumonic empyemas, and culture proven and biochemically proven empyemas showed no significant difference in procedure success rates or length of hospital stay. CONCLUSION: Multiple therapeutic options exist for the treatment of thoracic empyema. Optimal therapy requires selection of the most appropriate first procedure for each patient with early postprocedure imaging to avoid inordinate delays between interventions. PMID- 7781344 TI - Familial aggregates in obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome (OSAS) was diagnosed in157 subjects based on clinical symptoms, physical evaluation, cephalometric x-ray films, and polysomnography. These index cases identified 844 living first-degree relatives. Mailings were sent to 792 (94%). The mailing consisted of two identical questionnaires, one for the family member of the index case and one to be given to a friend (not a relative) of approximately the same age. In response, we received 531 (63%) questionnaires from relatives and 198 (25%) questionnaires from age-matched nonrelated friends, which were used as a control group. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay Area or vicinity. Two hundred seventy-nine relatives (100%) were identified. One hundred sixty-six subjects (59%) as well as 69 age-matched friends (ie, 41% of the 166 relatives and 25% of the potential total group) agreed to participate in further studies. These subjects had interviews, clinical investigations, and nonattended ambulatory monitoring. Cephalometric x-ray films could be obtained on only 22 of 166 participating relatives and 6 of 69 friends. Body mass index was not a differentiating measure between relatives and friends. Odds ratios (ORs) were calculated from the questionnaiare data. The report of tiredness, fatigue, and sleepiness did not distinguish family members from friends. The OR, however, progressively increases when there is a positive history of near nightly loud snoring (OR = 1.78; 95% confidence interval [CI] 1.25-2.54) or a positive history of daytime sleepiness in conjunction with near nightly loud snoring (OR = 3.11; 95% CI = 1.94-4.99). The investigation in the Bay Area indicated that, when first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow(ogival) hard palate sharply differentiated between friends and relatives (OR = 10.9, 95, CI = 5.31-22.5). An Epworth Sleepiness Scale score of 9 or greater with the presence of another symptom associated with OSAS, and a respiratory disturbance index greater than 5 (number of apneas and hypopneas per hour of sleep > 5) gave an OR of 45.6 (95% CI = 18.8-11.0). Disproportionate craniofacial anatomy was common in familial groups with OSAS. Craniofacial familial features can be a strong indicator of risk for the development of OSAS. PMID- 7781343 TI - Cardiac hypertrophy in obstructive sleep apnea syndrome. AB - Fifty-one middle-aged male patients with obstructive sleep apnea syndrome (OSAS) were evaluated using two-dimensional echocardiography, 24-h blood pressure measurements, polysomnography, and plasma norepinephrine (NE) measurements. Among these patients, left ventricular hypertrophy (LVH) (left ventricular posterior wall thickness [LVPWT] or interventricular septal thickness [IVST] > or = 12 mm) and right ventricular hypertrophy (RVH) (right ventricular wall thickness [RVT] > or = 5 mm) were present in 41.2% (21/51) and 11.8% (6/51). LVH was present in 50.0% of group 2 patients (apnea index > or = 20) and in 30.5% of group 1 patients (apnea index < 20). All patients with LVH had hypertension. RVH was present in 21.4% of group 2 patients and none of the group 1 patients. IVST, LVPWT, LV mass, LV mass/body surface area (BSA), and obesity index were significantly greater in group 2 than in group 1. Apnea index and the duration in which nocturnal oxygen saturation was decreased under 90% (duration of SaO2 < 90%), were significantly correlated with LV mass/BSA and 24-h mean blood pressure. Apnea index, number of apneas, duration of nocturnal oxygen saturation less than 90%, weight, and obesity index were significantly greater in patients with both LVH and RVH than in patients without LVH and RVH, or those with only LVH. Plasma NE after waking significantly increased compared with that before sleep (p < 0.05). The ratio of plasma NE levels after waking to those before sleep was significantly correlated with the duration of SaO2 < 90% (r = 0.83, p < 0.05), but not with apnea index. These results suggest that frequent episodes of oxygen desaturation and/or arousal responses caused by apnea may contribute to the complication of LVH and RVH in the long term, and apnea-induced cyclical increases in blood pressure and the resulting sustained elevation in blood pressure associated with the increase in afterload and sympathetic activity may play a role in the development of LVH. PMID- 7781345 TI - Sleep fragmentation in kyphoscoliotic individuals with alveolar hypoventilation treated by NIPPV. AB - Intermittent positive pressure ventilation (IPPV) delivered via nasal access can normalize alveolar ventilation for individuals with chronic alveolar hypoventilation (CAH) due to neuromuscular disease, spinal cord injury, or skeletal deformity. The purpose of this study was to evaluate the effect of nasal IPPV (NIPPV) air leakage-associated oxyhemoglobin desaturations (dSATs) on the sleep efficiency of kyphoscoliotic individuals with severe pretreatment nocturnal dSATs. Only individuals using nocturnal NIPPV without supplemental oxygen therapy were studied. Seven such individuals were able to maintain PaO2 greater than 60 mm Hg without supplemental oxygen therapy (five had been using oxygen therapy in the pretreatment period), had fewer hospitalizations, and had improvements in symptoms, arterial blood gas values, and nocturnal oxyhemoglobin saturation (SAT) by nocturnal NIPPV. This occurred despite polysomnographically observed sleep disruption and sleep stage changes associated with frequent transient dSATs and massive insufflation leakage. Arousals and dSATs were most frequent during rapid eye movement (REM) sleep with the latter occurring at a frequency of 10/h. The dSATs resulted in brief arousals or lightening of sleep stage 76% of the time. With or without arousal, central nervous system mediated reflex muscular activity occurred to diminish leak and normalize SAT. We conclude that the effectiveness of nocturnal NIPPV is dependent in part on central mediated muscular activity. PMID- 7781346 TI - A randomized comparison of 100-mg vs 500-mg dose of methylprednisolone in the treatment of acute asthma. AB - There have been conflicting reports comparing the effects of various doses of corticosteroids in the treatment of acute asthma. The purpose of this study was to compare 100 mg with 500 mg of methylprednisolone in the emergency department treatment of acute asthma. We studied 150 patients presenting to the emergency department with acute asthma. After baseline pulmonary function testing, patients were treated with oxygen and hourly administration of aerosolized albuterol. Patients were randomized to receive either 100 or 500 mg of methylprednisolone intravenously. Spirometry was repeated at 3 h, and again at 5 h for those patients whose dyspnea had not resolved after 3 h. There was no difference in the FEV1 between the 500-mg and 100-mg dose groups either before treatment (38.0% vs 32.6% of predicted normal) or after treatment (55.3% vs 51.9% of predicted normal). There was no difference in the percentage improvement in FEV1 with treatment between the 500-mg and 100-mg dose groups (65.0% vs 71.2%). Twenty-five percent of the patients in the 500-mg dose group were admitted to the hospital compared with 28% of patients in the 100-mg dose group (not significant). We conclude that the administration of a 500-mg dose of methylprednisolone offers no advantages over a 100-mg dose in the emergency department treatment of acute asthma. PMID- 7781347 TI - Health-care utilization after near-fatal asthma. AB - Near-fatal asthma has been repeatedly associated with an increased risk of premature death. Despite a higher risk, death after near-fatal asthma remains infrequent. Few studies have examined the long-term outcome of those who experience a near-fatal event but do not succumb to asthma. We therefore contacted patients who had an episode of near-fatal asthma 5 to 10 years earlier and documented their use of health-care services for asthma. Each index case was compared with two age-matched controls who had been hospitalized for severe but not near-fatal asthma within 2 years of the index case admission. Thirty-seven index cases and 74 control subjects were assessed. Demographics did not distinguish the two groups. Availability of primary care physicians and asthma specialists were similar. There was no difference in the frequency of hospitalizations, emergency room visits, or visits to physicians for asthma between the two groups. ICU admissions were extremely infrequent. Although the mean number of ICU admissions per subject were similar in the year preceding our contact (0.03 +/- 0.16 in each group), there was a trend toward ICU admissions occurring more often in the near-fatal group (0.62 +/- 1.67 vs 0.31 +/- 0.91 admissions/subject). Days away from work were more frequent in the control group (3.5 +/- 5.5 vs 1.6 +/- 3.3 d/yr) including days away from work in the year preceding our contact (8.9 +/- 43 vs 1.8 +/- 6.1 d). The data suggests that with regards to characteristics and health-care utilization, it may not be possible to distinguish people with near-fatal asthma from those who are hospitalized without a near-fatal event. PMID- 7781348 TI - The contribution of respiratory viruses to severe exacerbations of asthma in adults. AB - Viral infections are known to be associated with severe exacerbations of asthma in children. In contrast, there is limited data that viral infections evoke acute episodes of asthma that require emergency care in adults. To determine the role of viral infections in exacerbations of asthma in adults, we examined 33 patients who presented to the emergency room with 35 exacerbations of asthma between September 1990 and March 1991 for the presence of a viral infection. A nasal swab was obtained for virus isolation by culture and rapid antigen detection by fluorescent staining. In 16 patients, serum was collected at initial presentation and 3 to 4 weeks later for acute and convalescent viral antibody titers. All patients had acute episodes of asthma ascertained by medical history and physical examination. About 56% of the patients with asthma exacerbations had symptoms suggestive of viral illness. Rapid antigen detection and viral cultures for influenza A and B, parainfluenza-1, 2, 3, respiratory syncytial virus, adenovirus, and rhinovirus were negative on all patients. Likewise, in all 16 patients tested, acute and convalescent serologic studies did not show a significant rise in titer by complement fixation test. Thus, despite symptoms consistent with viral infection, viral pathogens could not be shown by current virologic techniques. This study suggests that viral infection may not be as prevalent a precipitate of asthma in adults requiring emergency room treatment as is generally thought. PMID- 7781349 TI - Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma. AB - STUDY OBJECTIVE: This study was conducted to determine whether intravenous magnesium sulfate (MgSO4), when used as part of a standardized treatment protocol, can improve pulmonary function and decrease admission rate in patients presenting to the emergency department with exacerbations of asthma. DESIGN: In this randomized double-blind placebo-controlled study, patients with acute asthma were treated with inhaled beta-agonists at regular intervals and intravenous (IV) steroids. At 30 min after entry, patients received either 2 g IV MgSO4 or IV placebo. Patients were monitored for up to 4 h with regular measurements of pulmonary function. Patients who were discharged from the emergency department were contacted at 1 day and 7 days for follow-up. SETTING: Emergency departments of a university-affiliated, voluntary hospital and municipal hospital. PARTICIPANTS: Asthmatics aged 18 to 65 years during acute exacerbation with FEV1 less than 75% predicted both before and after a single albuterol treatment. INTERVENTIONS: Patients were given 2 g of MgSO4 or placebo as an adjunct to standardized emergency department procedure for acute asthma. MEASUREMENTS AND RESULTS: One hundred thirty-five patients were studied. Hospital admission rates were 35.3% for placebo-treated group and 25.4% for the magnesium-treated group (p = 0.21). FEV1 measured at 120 min was 56% predicted for the placebo-treated group and 55% predicted for the magnesium-treated group. (p = 0.92) For subgroup analysis, patients were divided into "severe" (baseline FEV1 < 25% predicted on presentation) or "moderate" (baseline FEV1, 25 to 75% predicted on presentation). For the severe group, admission rates were 78.6% (11/14) for the placebo-treated group and 33.3% (7/21) for the magnesium-treated group (p = 0.009). For the moderate patients, admission rates were 22.4% (11/49) for the placebo-treated group and 22.2% (10/25) for the magnesium-treated group (p = 0.98). There was no significant improvement in FEV1 in the moderate group for magnesium-treated patients. However, in the severe group, there was a significant improvement in FEV1 at 120 min and 240 min (p = 0.014 and 0.026, respectively). CONCLUSION: Intravenous MgSO4 decreased admission rate and improved FEV1 in patients with acute severe asthma but did not cause significant improvement in patients with moderate asthma. PMID- 7781350 TI - Nasal function and bronchial hyperresponsiveness to methacholine in children. AB - The objective of the present study was to investigate nasal function by active anterior rhinomanometry with respect to spirometric data and bronchial hyperresponsiveness to methacholine in 9-year-old children. The study population consisted of 300 children (ages 8 to 11 years; mean, 9.3 years; 161 male, 139 female), who underwent basal rhinomanometry followed by a decongestion test and a lung function test consisting of spirometry and a methacholine provocation test. The flow values of the basal rhinomanometry showed a significant correlation with height and bronchial hyperresponsiveness. The consecutive decongestion test showed a marked increase in flow rates at each level, which was found to be significantly higher in children with bronchial hyperresponsiveness (p < 0.01). The spirometric data showed no influence on rhinomanometric values. These results suggest that nasal dysfunction and reactivity in terms of the decongestion test may be associated with bronchial hyperresponsiveness in children. PMID- 7781351 TI - Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with COPD. AB - STUDY OBJECTIVE: To evaluate the short-form 36-item questionnaire (SF-36) as an instrument for measuring health-related quality of life (HRQL) in patients with symptomatic COPD. DESIGN: Observational data at a single point in time. SETTING: Outpatient pulmonary clinic. PATIENTS: Fifty male patients with COPD and no significant comorbidity. MEASUREMENTS AND RESULTS: HRQL was assessed with the SF 36, which consists of 36 questions that cover nine health domains. Clinical ratings of dyspnea were measured by the multidimensional baseline dyspnea index (BDI). Pulmonary function tests included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal inspiratory mouth pressure (PImax). The mean (+/- SD) age of the patients was 72 +/- 8 years. The BDI focal score was 5.6 +/- 2.3, FEV1 was 1.32 +/- 0.60 L (48 +/- 22% pred), and PImax was 62 +/- 23 cm H2O. The BDI focal score was significantly correlated with seven of nine components of the SF-36 (range of r, 0.42 to 0.91; p < 0.05). The FEV1 percent of predicted and PImax were significantly correlated with five of nine health components (range of r, 0.30 to 0.65 and 0.31 to 0.61, respectively). Using linear regression model analysis with the different SF-36 components as the dependent variable and BDI, FVC, FEV1, and PImax as independent variables, the BDI score was the only significant predictor of social and physical functioning, role-physical, vitality, pain, health perceptions, and health transition (p < 0.05). CONCLUSIONS: The SF-36 is a valid instrument to measure HRQL in patients with COPD. The severity of dyspnea but not respiratory function was a significant predictor of various components of HRQL. PMID- 7781352 TI - Reproducibility of Borg scale measurements of dyspnea during exercise in patients with COPD. AB - The purpose of this study was to evaluate the moderate term (5 weeks) reproducibility of Borg scale ratings of the effort to breathe (Borge) and the degree of discomfort evoked by breathing (Borgd) in patients with COPD during exercise. Six subjects with moderately severe COPD (FEV1, 1.42 +/- 0.50 L) underwent progressive incremental exercise (15 W/min) on a cycle ergometer to a symptom-limited maximum every week for 6 weeks (first week used as practice session). Minute ventilation (VE), oxygen consumption (VO2), and Borg ratings were obtained every minute during exercise. Borge and Borgd were highly correlated in each subject (r = 0.99 +/- 0.01). Borg scores were not significantly different across study days during both maximal and submaximal exercise. The within-subject coefficient of variation (CV) for Borge during maximal exercise was 13.9 +/- 9.0% (range, 6 to 31%) which was not significantly different from that observed for the physiological indices: 8.2 +/- 4.1% (range, 4 to 15%) for VE and 5.2 +/- 3.4% (range, 1 to 10%) for VO2. In contrast, at 66% of the maximum workload, the within-subject CV for Borge was 25.0 +/- 13.6% (range, 12 to 50%) which was significantly greater than that observed for the physiologic indices: 5.8 +/- 2.0% (range, 3 to 9%) for VE and 4.6 +/- 1.1% (range, 3 to 6%) for VO2. In every subject, Borge was linearly correlated with VE, VO2, and workload. However, within an individual subject, the slope of these relationships varied between trials; within-subject CV for the slope of the Borge/VE relationship was 20.2 +/- 8.0% (range, 12 to 32%). In conclusion, during incremental exercise Borg ratings of dyspnea are not as reproducible as physiologic indices in patients with COPD. PMID- 7781353 TI - Diagnosis of pleural effusions. Experience with clinical studies, 1986 to 1990. AB - OBJECTIVES: To identify in patients with pleural effusion which procedures are most useful in separating malignant from nonmalignant pleural effusions and to identify which procedures most commonly lead to a definitive diagnosis. DESIGN: Prospective consecutive case series. SETTING: Pulmonary referral hospital in Prague, Czech Republic. PATIENTS: One hundred seventy-one adults between ages 18 and 70 years with a pleural effusion and a Karnofsky score of 70 or above. INTERVENTIONS: All patients underwent history, physical, pleural fluid cytologic study, laboratory evaluation of serum and pleural fluid, pleural biopsy, bronchoscopy, and lung scan and/or pulmonary arteriogram. RESULTS: In this series in which 45% of the patients had malignant effusions, 19% had paramalignant effusions, and 36% had benign diseases, the pleural fluid cytologic study was the best for establishing a diagnosis. The pleural fluid carcinoembryonic antigen (CEA) levels above 10 had a high specificity (90%) for malignancy but had low sensitivity (37%). The pleural fluid CEA level was increased only in 19% of patients with paramalignant effusions. Although there were statistically significant differences in the mean results on several biochemical tests of pleural fluid, none were very accurate in separating malignant from benign disease. CONCLUSION: From this study, we conclude that patients with an undiagnosed pleural effusion should be evaluated in an individualized stepwise manner. If malignancy is strongly considered, the initial three steps should be relatively noninvasive and include clinical evaluation and cytologic study. PMID- 7781354 TI - Comparative analysis of the biochemical parameters used to distinguish between pleural transudates and exudates. AB - The differentiation between exudates and transudates is the initial step in the analysis of pleural effusions as it often gives an indication of the underlying pathophysiologic process, the differential diagnosis, and the need for further investigations. Four classifications have been suggested in the literature: Light's criteria, serum-effusion albumin gradient, effusion cholesterol concentration, and pleural/serum bilirubin concentration. AIM OF STUDY: To compare the various biochemical parameters used to identify exudates. PATIENTS AND METHODS: A study was carried out from February 1993 to March 1994 at Tygerberg Hospital, South Africa. Five hundred pleural effusions and serum specimens were analyzed. After discharge, the hospital records of all patients were reviewed for a diagnosis. RESULTS: A reliable diagnosis could be made in 393 cases (270 exudates and 123 transudates). Using the criteria of Light and associates 93% of the effusions were correctly classified, yielding a sensitivity and specificity of 98% and 83%, respectively, to detect exudates. The serum effusion albumin gradient at a cutoff level of 12 g/L yielded the following results: accuracy, 89%; sensitivity, 87%; and specificity, 92%. Using a cutoff level of 1.55 mmol/L, the effusion cholesterol concentration yielded results of 70%, 54%, and 92%, respectively. The results improved at lower cutoff levels for effusion cholesterol level. Use of the pleural/serum bilirubin ratio as a means for identifying exudates produced results of 75%, 81%, and 61%, respectively. CONCLUSION: The criteria of Light et al remain the best method for distinguishing exudates from transudates. The serum-effusion albumin gradient is useful when patients are receiving concurrent diuretic therapy. PMID- 7781355 TI - Changes in pulmonary mechanics and gas exchange after thoracentesis on patients with inversion of a hemidiaphragm secondary to large pleural effusion. AB - The present study was designed to test whether there was a significant improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracentesis on patients with inversion of a hemidiaphragm due to pleural effusion. In 21 patients with inversion of a hemidiaphragm because of a pleural effusion, we studied the changes in pulmonary mechanics and gas exchange that occurred in 24 h after removal of 600 to 2,700 mL of fluid by thoracentesis. There was a small but significant increase in the forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (p < 0.001). The alveolar-arterial oxygen gradient (P[A-a]O2) and partial pressure of arterial oxygen (PaO2) showed a significant increase (p < 0.001), but there was no change in partial pressure of arterial carbon dioxide (PaCO2). In the present study, all patients with a large pleural effusion had inversion of a hemidiaphragm documented by chest sonography, and that was an important factor to observe significant improvement in pulmonary mechanics and gas exchange. PMID- 7781356 TI - Percutaneous needle biopsy of localized pulmonary, mediastinal, and pleural diseased tissue with an automatic disposable guillotine soft-tissue needle. Preliminary results. AB - Percutaneous needle biopsy (PNB) of localized thoracic disease has become a widespread procedure in many institutions. The development of special small caliber needles has increased the diagnostic yield of PNB partly by increasing the amount of tissue from biopsy, often enabling histologic examination. Nevertheless, in a significant number of patients only cytopathologic examination is possible on the retrieved biopsy fragments, necessitating the presence of a trained cytopathologist in the biopsy room. Furthermore multiple biopsy needle passages often are required, increasing the risk for complications such as pneumothorax. We have evaluated the use of a small-caliber tissue biopsy cutting needle, consistently yielding sufficient biopsy tissue for histologic examination. In 25 pleural and mediastinal lesions, which could be biopsied without passage through aerated lung, there was a 93% sensitivity (7% false negative results) for neoplasm and a 100% accuracy for benign disease. There were no complications. In 32 patients with lesions of 1 cm in diameter or more surrounded with aerated lung tissue, adequate histologic examination was feasible on every biopsy specimen after only one needle passage. There was an 87% sensitivity of PNB in neoplastic disease (13% false-negatives). In the patients with benign disease, there was a 100% accuracy. There was a 15.6% risk for pneumothorax. In only one patient (3%), however, was chest drainage necessary. One patient (3%) had mild hemoptysis. We conclude that percutaneous biopsy of localized pulmonary, pleural, and mediastinal lesions with a new small-caliber automatic guillotine cutting needle is safe and efficient, enabling recovery of sufficient tissue for histologic examination with a single-pass procedure, thus minimizing the risk for pneumothorax, eliminating the need for a cytopathologist in the biopsy room, and shortening the duration of the procedure. PMID- 7781357 TI - Prednisone as adjunctive therapy in the management of pulmonary tuberculosis. Report of 12 cases and review of the literature. AB - A retrospective chart review was conducted over a 5-year period (1988 to 1993) in a tertiary inpatient care center on the effects of the addition of prednisone to the treatment regimens of 12 patients with pulmonary tuberculosis who continued to spike high temperatures and lose weight while showing bacteriologic response to effective antituberculosis therapy. After exclusion of other causes of fever, all patients were treated with 20 to 60 mg of prednisone daily until normalization of temperature and clinical improvement. Analyzed data included twice weekly sputum bacillary count, temperature record every 4 h, weekly patient weight, serum albumin level, liver function tests, and chest roentgenogram. The patients continued to spike temperatures of 38.3 degrees C to 40.5 degrees C (mean +/- SD = 39.6 degrees C +/- 0.6 degrees C) even after 18 to 53 days (mean +/- SD = 33.9 +/- 9.8 days) of antituberculosis therapy. Within 24 h after the addition of oral prednisone, temperature decreased in all 12 patients from a daily highest spike mean of 39.6 degrees C +/- 0.6 degrees C (SD) to 38.1 degrees C +/- 0.6 degrees C (SD) (p = 0.0022). The duration of required prednisone therapy was 20.1 +/- 9 days (mean +/- SD). During this period patients' appetites improved, and their weight increased from a mean (+/- SD) of 53.6 +/- 5.7 kg to 58.1 +/- 6.4 kg (p = 0.0022). The serum albumin level increased from a mean (+/- SD) of 2.51 +/- 0.4 g/dL to 3.21 +/- 0.4 g/dL (p = 0.0033). All the patients also showed clinical evidence of a decrease in toxic reactions associated with tuberculosis. There were no side effects from the addition of prednisone. This study shows the need for randomized controlled clinical trials to clarify the role of prednisone as adjunctive therapy in the management of pulmonary tuberculosis. PMID- 7781358 TI - The utility of polymerase chain reaction (PCR) in the diagnosis of pulmonary tuberculosis. AB - A fragment of DNA of 123 bp belonging to insertion sequence IS6110, specific of Mycobacterium tuberculosis complex, was amplified by polymerase chain reaction (PCR) of respiratory samples, for the diagnosis of pulmonary tuberculosis. A total of 314 samples (286 sputum and 28 bronchoalveolar lavages) from 242 patients were evaluated by PCR, and the results were compared with the those obtained by acid-fast-stained smears, culture, and clinical diagnosis. Mycobacterium tuberculosis was detected by PCR in 102 of 105 patients with clinical diagnosis of pulmonary tuberculosis. All smear and culture-positive samples were PCR positive. The sensitivity of PCR, culture, and staining was 97%, 88%, and 65%, respectively, and the specificity was 100% in all cases. In ten patients with old residual lesions, but no active disease, M tuberculosis genome was detected by PCR. In our experience, PCR proved to be a useful method for the rapid diagnosis of pulmonary tuberculosis. PMID- 7781359 TI - Elevated levels of soluble ICAM-1 in serum and BAL fluid in patients with active sarcoidosis. AB - Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin superfamily of adhesion molecules, plays an important role in inflammatory and immune diseases. The soluble form of ICAM-1 (sICAM-1) shed from the cell surface may be a marker of inflammatory response and may reflect the disease activity. We measured the levels of sICAM-1 in serum and bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. Healthy volunteers were examined as controls. sICAM 1 concentrations were measured using an enzyme-linked immunosorbent assay kit with two different monoclonal antibodies. Serum and BALF sICAM-1 levels in sarcoidosis were significantly higher than those in control. Serum sICAM-1 levels correlated with serum soluble interleukin-2 receptor levels (a marker of T lymphocyte activation) but not with serum angiotensin-converting enzyme levels. sICAM-1 levels in BALF correlated significantly with the percentage of lymphocytes in BALF. Some patients were examined twice during follow-up periods. In patients in whom the chest radiograph improved, serum and BALF sICAM-1 levels decreased. However, in patients in whom the radiograph worsened, sICAM-1 levels increased. These results suggest that measurement of sICAM-1 may be useful to investigate not only the pathogenic mechanisms, but also the clinical status and disease activity in patients with sarcoidosis. PMID- 7781360 TI - Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. AB - Collagenases in bronchoalveolar lavage fluid (BALF) of patients with bronchiectasis and healthy subjects were characterized using specific functional and immunologic assays. The BAL fluid contained interstitial collagenase and collagenolytic proteinases of bacterial origin. Collagenase activities, obtained after organomercurial activation, correlated with the severity of bronchiectasis. In severe cases, collagenase activities were 3.5 x 10(-7) IU/L/48 h or 4.8 x 10( 6) IU/g/48 h (p < 0.01), in moderate ones 1.74 x 10(-7) IU/L/48 h or 3.35 x 10( 6) IU/g/48 h (p < 0.05), and in mild cases 0.32 x 10(-7) IU/L/48 h or 0.7 x 10( 6) IU/g/48 h (p < 0.05). The corresponding activities in healthy control subjects were 0.08 x 10(-7) IU/L/48 h or 0.13 x 10(-6) IU/g/48 h. The cellular origin of interstitial collagenase was assessed with doxycycline inhibition test utilizing the differential sensitivity of fibroblast-type collagenase/MMP-1 (IC50 = 280 microM) and neutrophil-type collagenase/MMP-8 (IC50 = 26 microM) to the anticollagenolytic, nonantimicrobial doxycycline action. Interstitial collagenase, contained in BALF, was totally inhibited by 100 microM of doxycycline. It can therefore be concluded that most of mammalian collagenase presented in inflamed fluid of bronchiectasis originated from neutrophils. The molecular forms of neutrophil-type collagenase/MMP-8 were confirmed and analyzed by Western-blot, which showed evidence of the proteolytic conversion of the latent 85-kD MMP-8 proenzyme species into active 65-kD molecular weight species. These findings strongly suggest involvement of proteolytic activation pathway of proMMP-8, especially in severe and moderate forms of bronchiectasis. Furthermore, collagenolytic proteases of bacterial origins may also participate in tissue destruction of the lung. PMID- 7781361 TI - Pulmonary barotrauma and related events in divers. AB - Although pulmonary barotrauma (PBT) is a well-known clinical entity, its recognition in divers is sometimes delayed and its implications for future diving often are unappreciated. The pulmonary complications of diving activities range from mere discomfort from mediastinal emphysema or pneumothorax, or both, to life threatening gas embolization. In nine cases described here, only minor manifestations were associated with PBT which occurred at or close to the surface, but three of these four divers were found to have abnormal pulmonary function. More serious manifestations resulted from PBT which took place at depths of 16 to 120 ft. Even minor forms of PBT should be considered a contraindication to further diving, since they are prone to recur. Such recurrences--even at shallow depths--may cause serious complications. PMID- 7781362 TI - Cerebral air embolism in asthmatic scuba divers in a swimming pool. AB - Significant shallow-water injuries can occur in scuba divers, even in swimming pools. Two asthmatic patients are presented who sustained cerebral air emboli during Scuba classes in a swimming pool. Such injuries may be more common in asthmatics. Asthma is a contraindication to Scuba diving. PMID- 7781363 TI - Endotracheal intubation by paramedics during in-hospital CPR. AB - STUDY OBJECTIVE: To examine whether well-trained paramedics can perform emergent, successful, uncomplicated, endotracheal intubations during in-hospital cardiopulmonary resuscitation (CPR). DESIGN: Retrospective review of medical records of in-patients undergoing emergent, endotracheal intubations during in hospital, CPR over 8 months, with comparison of the performance of the paramedics against that of other hospital-based personnel. SETTING: A 437-bed Midwestern community teaching hospital. PATIENTS: Adult in-patients in general medical/surgical wards. MAIN OUTCOME MEASURES: The rapidity of response of paramedics and other medical personnel to a cardiorespiratory arrest (code 4) announcement, and reported difficulties, success rate, rapidity, and complications of endotracheal intubation. RESULTS: In the 47 cardiorespiratory arrests requiring intubation that we analyzed, the median response times (with values in parentheses representing interquartile range [IQR]) for paramedics, nurse anesthetists (CRNAs), anesthesiologists, and other physicians respectively, were 2.00 (4.25), 4.00 (2.0), 4.00 (15.0), and 7.00 (8.0) min, requiring a median of 1.0 attempt for all groups (mean values, 1.4, 1.125, 1.0, and 1.4 respectively) to place an endotracheal tube. The paramedics were successful in 13 of 15 instances. Median times (seconds) required for intubation by various groups (same order as response times, with IQR given in parentheses) were 60 (30), 150 (270), 45 (30), and 60 (30). Difficulties were reported by all groups, including patients' resistance to intubation, airway obstruction by extraneous material, and difficulty in visualizing the glottis. Reported complications (4%) were confined to groups other than the paramedics. CONCLUSIONS: Paramedics can successfully, and without undue difficulty or complications, place endotracheal tubes during in-hospital CPR. Appropriately trained paramedics may be incorporated into hospital-based CPR teams in two contexts: (1) to provide an acceptable, long-term solution to the scarcity of personnel highly skilled in endotracheal tube placement during in-hospital CPR, and (2) to fulfill the need for hospitals to have on-site, qualified professionals to perform emergent endotracheal intubation during CPR. In the latter situation, personnel skilled in airway management could supplement the paramedics on demand. Further investigation in this area could be fruitful in view of the small sample size covered in this study. PMID- 7781364 TI - Evaluation of formulas for optimal positioning of central venous catheters. AB - OBJECTIVE: To evaluate the accuracy of formulas designed to estimate the optimum intravenous length of central venous catheters. DESIGN: A prospective study of catheter insertion sites to evaluate the accuracy of predetermined formulas that predict the intravascular insertion length required to avoid intracardiac catheter tip placement. SETTING: A 320-bed tertiary hospital. PATIENTS: Critically ill patients requiring central venous access for therapy or monitoring. MAIN RESULTS: The formulas accurately predicted required intravascular length of the central venous catheter in 217 of 228 (95%) cases. The formula for predicting catheter length was most accurate when the subclavian vein was used. It was least accurate when the right internal jugular vein was selected. CONCLUSIONS: The formulas can accurately predict the required length of catheters and thereby reduce the possibility of complications and save time and expense. PMID- 7781365 TI - Pressure support ventilation attenuates the cardiopulmonary response to an acute increase in oxygen demand. AB - Critically ill patients undergo interventions, such as chest physical therapy, that acutely increase metabolic rate. Previous observations revealed that chest physical therapy is accompanied by increases of 40 to 50% in oxygen consumption (Vo2) and 40% in minute ventilation contributes to the rise in Vo2 and its associated hemodynamic responses. This was done by increasing mandatory ventilatory support during the chest physical therapy session: In phase 1 the mandatory ventilation rate was increased by 35% and in phase 2 pressure support ventilation 15 cm h2O was added. In phase 1 (n = 12), the increase in mandatory rate did not attenuate the chest physical therapy induced rises in heart rate, arterial blood pressure and Vo2. The increase in minute ventilation when the mandatory rate was increased prevented a rise in PaCO2. In phase 2 (n = 15), no change in the increase in Vo2 with chest physical therapy was observed with the addition of pressure support. Yet the rises in heart rate and systemic and pulmonary artery pressures were attenuated, as was the increase in PaCO2. Respiratory rate did not increase as much with pressure support. There appears to be a role for pressure support ventilation in attenuating the pulmonary and hemodynamic responses to interventions that increase oxygen demand. PMID- 7781366 TI - Investigating the impact of age on outcome of mechanical ventilation using a population of 41,848 patients from a statewide database. AB - STUDY OBJECTIVE: To examine the impact of age on outcome from mechanical ventilation. DESIGN: Retrospective analysis of a statewide database. SETTING: All acute-care hospitals in New York State. PATIENTS: All patients, aged 18 years and over, requiring mechanical ventilation during 1990 who could be identified with a mechanical ventilation procedure code (93.92) were studied. Data were obtained in aggregate form (six or more cases) from the New York State Department of Health. This process required a detailed request letter to the Statewide Planning and Cooperative System (SPARCS). Transmission of confidential information was not desired or permitted. MEASUREMENTS AND RESULTS: Age and mortality rate (MR) fit a cuboidal regression model best (MR = -25.55 + 3.98Age - 0.072Age2 + 0.00043Age3, R2 = 0.85). Mortality rates vary significantly across various broad diagnostic groups (p < 0.01, analysis of variance [ANOVA]) and increase as a function of ICU duration (p < 0.01, ANOVA). CONCLUSIONS: Age has an important effect on outcome from mechanical ventilation. Other factors, such as ICU duration and diagnosis, also influence outcome, and age should not be used as a sole criterion in evaluating the potential benefit of mechanical ventilation to an individual patient. Large, existing databases, such as SPARCS, may be useful in studying the application of mechanical ventilation. PMID- 7781367 TI - Transferrin concentrations in serum and lower respiratory tract fluid of mechanically ventilated patients with COPD or ARDS. AB - Transferrin serves as the primary iron transport protein in serum, but it also is present in the lower respiratory tract where it has antioxidant and antibacterial properties. Prior studies indicate that patients with respiratory failure (RF) due to ARDS have increased concentrations of transferrin in the lower respiratory tract, which is attributed to increased lung vascular permeability. It is unclear whether mechanical ventilation contributes to increased lung transferrin content in patients with ARDS, although mechanical ventilation may increase lung microvascular permeability. To assess whether mechanical ventilation in patients with RF due to causes other than ARDS is also associated with increased respiratory tract concentrations of transferrin, we compared transferrin concentrations in serum and lung lavage fluid obtained from 12 mechanically ventilated patients with RF attributable to COPD, 6 patients with ARDS, and 15 healthy volunteers. Serum transferrin concentrations in patients with RF due to COPD were variable, but mean concentrations were similar to those in control subjects (336 +/- 58 vs 307 +/- 9 [SE] mg/dL), whereas serum transferrin concentrations were decreased in patients with ARDS (182 +/- 68 mg/dL; p < 0.05). Compared with control subjects, lavage fluid recovered from patients with RF due to COPD contained significantly decreased concentrations of transferrin (1.56 +/- 0.24 vs 4.27 +/- 0.44 micrograms/mL; p < 0.001), whereas transferrin concentrations in lavage fluid recovered from patients with ARDS were increased (15.72 +/- 2.01 micrograms/mL; p < 0.001). Transferrin concentrations of lavage fluid also were decreased in COPD patients when normalized for lavage fluid protein content (4.35 +/- 0.72 vs 19.96 +/- 3.13 micrograms/mg in control subjects, p < 0.001). These data indicate that mechanical ventilation of patients with COPD is associated with decreased lung transferrin concentrations, in contrast to an increased transferrin concentration found in patients with ARDS. Decreased transferrin concentrations in the lower respiratory tract may decrease defenses against oxidant injury and bacterial infection in patients with RF due to COPD. PMID- 7781368 TI - Enteral feeding tube placement success with intravenous metoclopramide administration in ICU patients. AB - OBJECTIVE: The purpose of this study was to determine if intravenous push metoclopramide would facilitate immediate transpyloric passage of a small-bore feeding tube without fluoroscopy or endoscopy. DESIGN: Prospective, randomized trial. PATIENTS: One hundred five medical and surgical ICU patients at a community teaching hospital. INTERVENTIONS: Patients were randomized to receive 10 mg of metoclopramide 10 min before tube insertion or no medication. MEASUREMENT: Successful placement was stated as radiologically verified transduodenal tube location. RESULTS: A 54% success rate was shown with administration of the drug with 46% success for the control. Chi square analysis of the success rate showed no significant relationship between administration of metoclopramide and successful tube placement (p = 0.38). Increasing years of physician training was the only variable associated with successful placement (p = 0.003). No association was found between successful tube placement and presence of endotracheal tube, tracheostomy, or cervical immobility, nor any interaction of metoclopramide with these variables. CONCLUSION: Intravenous metoclopramide, 10 mg, administered 10 min prior to intubation with a small-bore feeding tube (10F), was ineffective in facilitating transpyloric intubation. PMID- 7781369 TI - Intravenacaval membrane oxygenation and carbon dioxide removal in severe acute respiratory failure. AB - STUDY OBJECTIVE: To characterize the physiologic response to, and safety of, intravenacaval membrane oxygenation and carbon dioxide removal. DESIGN: Interventional before-after study. SETTING: University teaching hospital ICU. PATIENTS: Twenty-two patients with severe acute respiratory distress syndrome (ARDS). INTERVENTIONS: Implantation of a hollow-fiber membrane oxygenator (IVOX; CardioPulmonics; Salt Lake City, Utah) into the superior and inferior venae cavae by venotomy of the right femoral or right internal jugular vein for a duration of up to 20 days. MEASUREMENTS: Hemodynamic measurements using pulmonary artery and systemic artery catheters, ventilator settings (FIO2, minute ventilation, peak inspiratory pressure, and positive end-expiratory pressure), arterial and mixed venous blood gases (pH, PCO2, PO2, and measured saturation), and clinical laboratory determinations (CBC, fibrinogen, plasma hemoglobin, complement C3 and C5) were obtained. Calculations of PaO2/FIO2 ratio and PaCO2-VE product were used to assess gas exchange efficacy. Microbiologic cultures were obtained from the device and wound following explantation. Survival to ICU discharge and hospital discharge were recorded. RESULTS: Implantation was successful in 20 of 22 patients. Gas exchange rates averaged 50.4 +/- 15.8 mL.min-1 for carbon dioxide and 71.1 +/- 20.2 mL.min-1 for oxygen. A reduction in FIO2 from 0.78 +/- 0.16 to 0.63 +/- 0.21 and in VE from 177 +/- 94 mL.kg-1.min-1 to 127 +/- 58 mL.kg-1.min-1 was possible within 4 h post-implantation. By 12 h, FIO2 was reduced to 0.57 +/- 0.18. Indices of gas exchange improved significantly after implantation, with PaO2/FIO2 ratio increasing from 79 +/- 20 to 112 +/- 47 and PaCO2-VE product decreasing from 7.6 +/- 4.2 to 4.9 +/- 2.5 within 4 h. A significant reduction in peak inspiratory pressure was achieved (45 +/- 10 to 38 +/- 9 cm H2O). Major complications were blood loss during implantation requiring transfusion in 11 patients, a retroperitoneal bleed in 1 patient, and femoral deep venous thrombosis in 4 patients, but there were no long-term sequelae or IVOX-related deaths. The ICU and hospital survival were 10/20 (50%) and 8/20 (40%), respectively. CONCLUSIONS: Intravenacaval membrane oxygen and carbon dioxide removal can provide partial respiratory support during severe respiratory failure and permit reductions in the level of mechanical ventilator support, with an acceptable safety profile. PMID- 7781370 TI - Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock. AB - STUDY OBJECTIVE: To examine the hemodynamic and metabolic short-term effects of hypophosphatemia correction in patients with septic shock receiving catecholamine therapy. DESIGN: Prospective, single cohort study. SETTING: ICU, university hospital. PATIENTS: Ten patients with septic shock and hypophosphatemia below 2 mg/dL. INTERVENTIONS: Infusion of glucose-1-phosphate solution (20 mmol of elemental phosphorus) for 60 min. MEASUREMENTS AND RESULTS: Hemodynamic, oxygen derived, acid-base, and electrolyte parameters before and immediately after phosphate infusion. Left ventricular stroke work index increased significantly (22%) from a mean low value of 24 +/- 10 g/m2 without changes in filling pressures. Systolic arterial pressure improved by 12%. Arterial pH improved slightly but significantly. Ionized calcium level slightly decreased within the normal range values. Other parameters remained unchanged. CONCLUSIONS: Severe hypophosphatemia may be considered as a superimposed cause of myocardial depression, inadequate peripheral vasodilatation, and acidosis in septic shock. A rapid correction of hypophosphatemia is well tolerated and may have both myocardial and vascular beneficial effects. The magnitude of the response, however, is variable and unpredictable on the basis of serum phosphorus levels. PMID- 7781371 TI - Talc slurry is an effective pleural sclerosant in rabbits. AB - Insufflated talc is probably the most effective agent for creating a pleurodesis both in the clinical situation and in animals. However, the insufflation of talc requires an invasive procedure such as thoracoscopy or thoracotomy. Recently, there have been reports that talc in a slurry was effective in the clinical situation. The objective of this project was to determine whether talc in a slurry at varying doses is an effective sclerosant in an experimental model in rabbits. Talc, 50, 100, 200, and 400 mg/kg, in a 2-mL slurry was injected intrapleurally through a small catheter in male rabbits. Eleven rabbits received each dose. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis (on a scale of 0 to 4) after the injection of 50, 100, 200, and 400 mg/kg of talc was 1.1 +/- 0.9, 1.5 +/- 1.1, 2.7 +/- 0.6, and 3.4 +/- 0.5, respectively. The degree of microscopic fibrosis similarly increased with increasing doses of talc. These scores were similar to those we have reported with the tetracycline derivatives. In contrast to the results with tetracycline derivatives, none of the rabbits developed fibrothorax or hemothorax. From this study, we conclude that talc in a slurry is a very effective pleural sclerosant in rabbits and does not produce hemothoraces as do the tetracycline derivatives. PMID- 7781373 TI - Sleep in the intensive care unit. AB - The most critically ill patients in the hospital are located in the ICU. Due to intensive individualized care and monitoring, these patients often suffer from severe sleep deprivation. The amount and continuity of sleep as well as normal sleep architecture are all affected. Moreover, by impairing protein synthesis, cell division, and cellular immunity, sleep deprivation can affect the healing process and thus contribute to an increased morbidity and mortality. Reasons for sleep deprivation appear to be multifactorial and include the following: the patient's chronic underlying illness, an acute superimposed illness or surgical procedure, medications used in treatment of the primary illness, and the ICU environment itself. Therapeutic interventions need to address each of these potential causes, with an emphasis placed on providing an environment that is both diurnal and focused on the importance of uninterrupted sleep. PMID- 7781372 TI - Talc slurry pleurodesis. Pleural fluid and histologic analysis. AB - Although talc slurry pleurodesis is effective for control of malignant pleural effusions and recurrent pneumothorax, the mechanisms of pleurodesis remain incompletely defined. We instilled 70 mg/kg of sterile asbestos-free talc slurry into the pleural space of New Zealand white rabbits and studied the inflammatory response at 1, 2, 3, 7, 15, 30, 60, 90, and 120 days by observing pleural fluid and histologic characteristics. Talc slurry caused mesothelial denudement and an exudative neurotrophilic pleural effusion that resolved after 48 h. A transient mononuclear vasculitis was seen within the lung at 1, 2, and 3 days after instillation. Pleural adhesions were minimal and did not increase in number over time. Talc was found outside of the pleural space in mediastinal lymph nodes (4 of 23 animals examined), kidney (1 of 6), and spleen (4 of 10). The predominant cause of pleurodesis with talc slurry instillation is an acute pleural injury similar to the tetracycline class agents. PMID- 7781374 TI - What is acute lung injury? What is ARDS? PMID- 7781375 TI - Review of the Kilburn and Warshaw Chest article--airways obstruction from asbestos exposure. PMID- 7781376 TI - Airways obstruction from asbestos exposure and asbestosis revisited. PMID- 7781377 TI - Acute myocardial infarction. Then and now. AB - Dramatic changes in the management of acute myocardial infarction (AMI) have occurred in the past decade. While previous management strategies were primarily supportive, current strategies focus on achieving and maintaining patency of the infarct-related artery restoring blood flow to jeopardized myocytes, preserving left ventricular function, and preventing recurrences and complications in addition to promoting healing. Restoration of blood flow can be achieved pharmacologically with thrombolytic agents or mechanically with percutaneous transluminal coronary angioplasty (PTCA). Early use of antiplatelet agents and anticoagulants helps maintain patency of the infarct-related arteries and prevents thromboembolic complications. Administration of beta-blockers and angiotensin enzyme inhibitors are more specific means of conserving myocardium and preserving ventricular function. Additionally, several strategies for preventing arrhythmias such as prophylactic lidocaine use and routine long-term suppression of premature ventricular contractions with antiarrhythmic drugs are no longer routinely advocated. Basically, in the era prior to the eighth decade of this century, the primary direction of the therapeutic strategy for AMI was to reduce the oxygen demands in the infarcted myocardium; whereas in the subsequent years, the emphasis shifts to improvement in oxygen delivery, via thrombolysis, PTCA, and coronary artery bypass graft surgery. These interventional changes, when added to greater sophistication in the use of drugs to reduce oxygen demands, resulted in significant lowering of myocardial mortality. PMID- 7781378 TI - Benign tumors of the tracheobronchial tree. Endoscopic characteristics and role of laser resection. AB - We conducted a review of all the bronchoscopies performed at our institutions for benign tumors from 1980 to 1991 to determine the endoscopic characteristics of these lesions. We reviewed the charts, the endoscopic characteristics from our video records, and finally the pathologic findings of these cases. We tried to identify the effectiveness of laser resections in each group. Of a total of 3,937 patients, 185 (4.7%) were benign tumors. On these patients, 317 procedures were carried out. There were 3 myoblastomas, 53 papillomas, 1 adenoma, 8 chondromas, 4 fibromas, 45 hamartomas, 15 hamartochondromas, 6 lipomas, 19 angiomas, 5 leiomyomas, 4 schwannomas, 1 neurofibroma, and 21 amyloidomas. Results of laser resection were "very good" in 115 (62%) and "good" in 70 (38%). Complications were minimal: two mediastinal emphysemas, one pneumothorax, and one anesthesia related cardiac arrest leading to the single death in this series. In general, benign tumors of the proximal endobronchial tree responded well to laser resection when their endoscopic appearance is recognized and prognosis known. Even when recurrent, repeated procedures can be performed easily with good results. This series is probably the largest in the world's literature about endoscopic recognition and the role of laser resection in patients presenting with benign endobronchial tumors. PMID- 7781379 TI - Pneumonia and infraorbital abscess in a 29-year-old diabetic pregnant woman. PMID- 7781380 TI - A 21-year-old man with cystic fibrosis. PMID- 7781381 TI - Posterior mediastinal mass in a patient with chest pain. PMID- 7781382 TI - Occult hypercarbia. An unrecognized phenomenon during percutaneous endoscopic tracheostomy. AB - Bronchoscopy has been incorporated as a useful adjunct to increase the safety and effectiveness of percutaneous endoscopic tracheostomy (PET). Insertion of the bronchoscope, along with the intraluminal dilators of the PET set, into the airway potentially leads to hypoventilation and hypercarbia during the procedure. Using continuous in-line arterial blood gas monitoring, we documented profound hypercarbia in two patients undergoing PET in the surgical ICU. In a third patient, the rise in PaCO2 was accompanied by a marked rise in intracranial pressure (ICP), and a corresponding fall in cerebral perfusion pressure. While transient hypercarbia seems well tolerated by most patients, this phenomenon and its effect on cerebral blood flow should be strongly considered before performing PET on the critically ill patient with evidence of elevated ICP. PMID- 7781383 TI - Fluoxetine hydrochloride (Prozac)-induced pulmonary disease. AB - We describe a patient who developed progressive dyspnea, lung infiltrates, and restrictive lung disease in association with the antidepressant fluoxetine hydrochloride (Prozac). The pathologic findings were consistent with hypersensitivity pneumonitis. An associated pulmonary phospholipidosis was also noted. PMID- 7781384 TI - Acute myocardial infarction while using the nicotine patch. AB - A 39-year-old man developed an acute myocardial infarction 20 days after starting treatment with nicotine patches. He had not smoked while using the patches. He recovered without complications. Coronary angiography did not reveal coronary stenoses. He had no history of myocardial infarction, hypertension, or diabetes mellitus. Although coincidence cannot be excluded, it is recommended that all patients should be strongly advised not to smoke while using the nicotine patch and to consult a physician if chest pain develops. PMID- 7781385 TI - Independent ventilation and ECMO for severe unilateral pulmonary edema after SLT for primary pulmonary hypertension. AB - Single lung transplantation (SLT) is now accepted therapy for selected cases of severe pulmonary hypertension. A recognized complication is the postoperative development of reperfusion edema in the graft, a potentially fatal cause of respiratory failure. Because reperfusion edema may be a reversible process, temporizing support measures can be life-saving. We report the case of a 48-year old woman who developed severe reperfusion edema following right SLT for primary (unexplained) pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) was instituted. Independent lung ventilation was later begun and resulted in markedly improved oxygenation allowing withdrawal of ECMO. We conclude that reperfusion edema following SLT for pulmonary hypertension may be uniquely amenable to treatment with independent lung ventilation and ECMO if needed. PMID- 7781386 TI - Correlate clinical findings with hemodynamic findings. PMID- 7781387 TI - Inhaled drug consumption and asthma mortality in Greece. PMID- 7781388 TI - Occupational asthma caused by pea flour. PMID- 7781389 TI - Adenosine deaminase in pleural effusions. PMID- 7781390 TI - The tracheotomized patient. Tracheal toilet and speech. PMID- 7781391 TI - A matter of terminology. Alveolar-arterial oxygen gradient. PMID- 7781392 TI - Fistulas do not always cause pericardial effusion. PMID- 7781393 TI - Tuberculosis in young adults and the elderly. PMID- 7781394 TI - Pleural tuberculosis in HIV-infected patients. PMID- 7781395 TI - Multimodality Therapy of Chest Malignancies. Proceedings of a symposium. Boston, Massachusetts, April 7-9, 1994. PMID- 7781396 TI - A neoadjuvant approach to esophageal cancer. AB - Patients with symptomatic esophageal cancer represent a significant challenge to the thoracic clinician, whether medical oncologist, surgeon, or radiation therapist. Historically, cure has been rare and palliation has been a more realistic goal. Surgery was often viewed as radical or risky as limited long-term survival was weighed against expected operative morbidity and mortality. Epidermoid tumors were minimally responsive to available chemotherapy. Primary radiotherapy achieved similar overall survival; however, recurrent dysphagia limited its palliative benefit. PMID- 7781397 TI - Thoracoscopic staging and surgical therapy for esophageal cancer. AB - Esophageal cancer continues to be a major health problem with an associated poor prognosis. New technology is being applied to the staging of this cancer. The new staging system requires assessment of depth of wall penetration and lymph node status prior to resection. To determine penetration and node status with a high degree of accuracy generally requires some combination of chemotherapy, magnetic resonance imaging, endoesophageal ultrasound, and/or surgical staging. Several variables need to be considered in planning the surgical approach to the patient with esophageal cancer: the intent of the surgeon to either cure or palliate, the anatomic location of the tumor, and the method of reconstruction. Surgery is optimal for localized esophageal cancer. Neoadjuvant chemoradiation has increased survival in specific subgroups. Phase 2 trials have shown the safety and efficacy of chemoradiation. Randomized multi-institutional trials are needed to verify the encouraging results of recent phase 2 trials. PMID- 7781398 TI - Chemotherapy and combined-modality therapy for esophageal cancer. AB - Treatment of esophageal carcinoma with radiation alone or surgery alone has yielded unsatisfactory cure rates and has not had a major impact on survival. The failure to cure or prolong survival of patients with esophageal cancer is because of our inability to eradicate residual disease at the primary site and to early systemic dissemination of disease. Three neoadjuvant approaches involving chemotherapy have been studied in patients with apparently localized esophageal cancer: preoperative chemotherapy followed by surgery, chemotherapy and concurrent radiation therapy followed by surgery, and chemotherapy and radiation therapy without surgery. All of these approaches have shown potential in pilot trials. Large-scale trials comparing surgery alone with chemotherapy prior to operation are underway. For patients with local-regional epidermoid carcinoma who are not able to undergo or who refuse operation, chemotherapy plus concurrent radiation appears, in random assignment trials, to be superior to radiation alone. PMID- 7781399 TI - The role of radiation therapy in treating patients with potentially resectable carcinoma of the esophagus. AB - Radiotherapy (RT) in conjunction with surgery may have a number of roles in the treatment of patients with potentially resectable esophageal carcinoma. The use of RT alone either preoperatively or postoperatively can be expected to improve resectability rates only modestly. The risk of locoregional failure, a common problem in esophageal carcinoma, has been substantially reduced with preoperative or postoperative RT in trials with a duration of follow-up of 3 or more years, although this effect has not been seen in trials with shorter follow-up. Because of the high risk of distant failure associated with these tumors and perhaps because of the inadequate doses used, most trials of RT have not shown notable improvements in overall survival rates. The risk of severe complications following preoperative or postoperative RT is small, provided that very high doses or fraction sizes are avoided. Concurrent chemotherapy and RT administration have been shown to be superior to RT alone in patients who have medically or surgically inoperable conditions; randomized trials using this combined modality in patients with resectable disease have only recently begun. In addition to evaluating the efficacy of this approach, investigators hope to establish the optimal sequencing and timing of administration of these modalities with regard to each other and to surgery. PMID- 7781400 TI - Small cell lung cancer. Case report. AB - The selection of appropriate chemotherapeutic and/or radiation therapy for small cell lung cancer should be done after careful diagnosis and staging workup. A patient with small cell lung cancer is presented and explanation given for each step in diagnosis and staging. PMID- 7781402 TI - Thoracic and cranial radiotherapy for limited-stage small cell lung cancer. AB - Chemotherapy remains the mainstay of treatment for small cell lung cancer (SCLC). For patients with limited-stage disease, the addition of thoracic radiotherapy confers a moderate improvement in local control and a modest survival benefit, but these improvements come at the cost of increased toxic reactions. The optimal method for integrating chemotherapy and thoracic radiotherapy is unresolved. Concurrent and alternating strategies are appealing because they allow uninterrupted delivery of chemotherapy, but they have not been proven to be superior to conventional sequential approaches. Based on limited data, delivery of thoracic radiation early in the treatment course may be preferable to delivery later in the course. There is evidence of a radiation dose-response effect for SCLC, and, in standard regimens, thoracic radiation doses in the range of 50 to 60 Gy are recommended. The use of limited radiation fields (to postchemotherapy tumor volumes) appears reasonable. Results for alternative thoracic radiation fractionation schedules such as accelerated hyperfractionation are promising and worthy of further investigation. The role of prophylactic cranial irradiation (PCI) is controversial and should be individualized. It should be considered for the favorable subgroup of patients with limited-stage disease who achieve a complete response to chemotherapy and thoracic radiotherapy. If given, we recommend a total dose of 30 to 36 Gy in 2-Gy fractions; PCI should not be delivered concomitantly with chemotherapy. PMID- 7781401 TI - Small cell lung cancer. State-of-the-art therapy 1994. AB - In the United States, small cell lung cancer (SCLC) accounts for about 20% of all cases of lung cancer. Without treatment, tumor progression in patients with SCLC is rapid, with a median survival of 2 to 4 months. Modern chemotherapy has yielded multifold increases in median survival, but only minimal improvements have occurred over the last decade. Combination chemotherapy with etoposide/cisplatin prolongs survival, especially in patients with limited disease. In patients at high risk of toxicity from standard combination chemotherapy, single-agent chemotherapy may have a viable role, but whether its efficacy is comparable to combination regimens must be established in clinical trials. Clearly, new, more effective drugs will be required for any major improvements in the treatment of SCLC. Combined-modality therapy employing chemotherapy and chest irradiation appears to produce excellent cytotoxic effects and is relatively well tolerated in patients with limited disease. A recent meta analysis of 13 randomized trials showed a modest but significant 14% reduction in the relative mortality rate of patients receiving chemotherapy/chest irradiation vs those receiving chemotherapy alone. Surgery as sole treatment can produce cures in highly selected patients with limited disease and can reduce the rate of local recurrence. The use of surgery after definitive treatment remains experimental and should not be considered other than in controlled clinical trials. PMID- 7781403 TI - Dose-intensive therapy for small cell lung cancer. AB - Enhancement of dose and dose intensity increases tumor response and may enhance long-term progression-free survival in patients with small cell lung cancer. Several strategies are identified to intensify therapy safely: a traditional induction/intensification mode, in which high-dose therapy with hematopoietic stem cell support is used to treat patients responding to conventional-dose therapy; and multicycle dose-intensive approaches, in which higher-dose therapy is administered over multiple cycles at initiation of therapy. This paper reviews some of the recently completed and activated trials (particularly those developed at the Dana-Farber Cancer Institute) exploring these concepts. PMID- 7781404 TI - Prognostic issues in non-small cell lung cancer. PMID- 7781405 TI - Chest X-ray screening improves outcome in lung cancer. A reappraisal of randomized trials on lung cancer screening. AB - It is believed that population-based screening for cancer should be advocated only when screening reduces disease-specific mortality. Four randomized controlled studies on lung cancer screening have been conducted in male cigarette smokers, and none has demonstrated reduced mortality. Accordingly, no organization that formulates screening policy advocates any specific early detection strategies for lung cancer. Yet, despite this public policy against screening, there is considerable evidence that chest x-ray screening is associated with earlier detection and improved survival. Two randomized trials, the Memorial Sloan-Kettering and Johns Hopkins Lung Projects, were specifically designed to evaluate the effectiveness of sputum cytologic study. Both evaluated the efficacy of the addition of sputum cytologic studies to annual chest radiographs, and both demonstrated that cytologic study did not favorably influence outcome. All individuals in experimental and control groups in both studies had annual chest radiographs. Because survival rates observed in both studies were about three times higher than predicted, based either on the National Cancer Institute's Surveillance Epidemiology and End Results database or based on the American Cancer Society's annual Cancer Statistics, raises the possibility that the periodic chest radiographs performed in all patients in both studies contributed to an improved outcome. In the Mayo Lung Project and in the Czechoslovak study on lung cancer screening, the experimental groups underwent a program of relatively intensive and regular rescreening with chest radiographs and sputum cytologic study, while the control groups underwent either less frequent rescreening or no rescreening. In both studies, the screened groups achieved meaningful improvements in stage distribution, resectability, and survival. However, increases in cumulative incidence of lung cancer in the experimental group in both studies (which in the Mayo Lung Project reached statistical significance) prevented significant improvements in survival from translating into corresponding reductions in mortality. The possibility that screening may be associated with lung cancer "overdiagnosis" has been widely postulated to account for higher survival and incidence rates and equivalent mortality rates. However, analysis of autopsy information and of disease outcome in individuals with screen-detected early stage lung cancer who do not undergo surgical resection strongly supports the conclusion that screening does not lead to overdiagnosis of lung cancer. Similarly, lead-time and length bias do not adequately account for the differences in cumulative incidence observed in the Mayo and Czech studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7781406 TI - Molecular markers in early cancer detection. New screening tools. AB - Better early detection strategies for lung cancer are clearly needed. About 20 years ago, cytomorphologic criteria were developed for use in staging bronchial epithelium carcinoma. Yet, when sputum cytology was added to chest radiograph in the largest early-screening-of-lung-cancer study carried out to date, the three arm trial sponsored by the National Cancer Institute, no major outcome benefit was shown. Sputum samples of participants in one of these trials, the Johns Hopkins Lung Project, have been archived. Currently, sputum immunostaining using two monoclonal antibodies directed at a difucosylated Lewis X epitope and a 31 kilodalton protein show correlation between positive staining of these samples and eventual development of lung cancer in the sampled population. Strategies to neutralize the stimulation of growth factors like gastrin-releasing peptide, which are seen in small-cell disease, are also being explored. Development of an epithelial-directed diagnostic test is the most important goal in obtaining early detection tools for lung cancer. Several new tests await prospective trials to evaluate their utility. In developing an early detection test for lung cancer, due to the chronic nature of the risk and the vast at-risk population, cost and patient compliance are two major concerns. PMID- 7781407 TI - Biologic and molecular prognostic factors--impact on treatment of patients with non-small cell lung cancer. AB - A wide range of genetic and phenotypic abnormalities have been identified in lung cancer. However, only a few are known to have an impact on patient outcome and thus may influence choice of therapy. Biologic and molecular factors known in this regard include the epidermal growth factor family and its receptors, markers of neuroendocrine differentiation in non-small cell lung cancer, and mutations of the ras gene family. None of these factors, however, can be considered a standard for selection of patients for therapy until additional information is gleaned from ongoing prospective studies. PMID- 7781408 TI - Locally advanced lung cancer. Case presentation. PMID- 7781409 TI - Radiologic evaluation in chest malignancies. A review of imaging modalities. AB - Radiologic evaluation of the patient with non-small cell lung cancer (NSCLC) includes chest radiographs for detecting nodules, computed tomography (CT) for further characterizing them, CT and magnetic resonance imaging (MRI) to evaluate the mediastinum, and extrathoracic imaging of bones, the adrenal gland, the central nervous system, and liver. The current practice standards for each are reviewed. Asymptomatic solitary pulmonary nodules, which are usually detected on chest radiographs obtained for other indications, inevitably require a precise diagnosis. The radiologic characteristics that differentiate benign from malignant pulmonary lesions are given. Mediastinal CT is the preferred modality for examining the mediastinum in patients with NSCLC. Magnetic resonance imaging is used selectively, eg, in patients with superior sulcus tumors who are candidates for surgery. When evaluation for N2/N3 disease is requested, mediastinoscopy should replace CT using the latter as a "roadmap." The role of extrathoracic imaging in evaluating asymptomatic patients with NSCLC at initial presentation is equivocal. Computed tomographic scanning of the head is reasonable in most patients with lung cancer, given the significant incidence of occult brain metastases in this population and that solitary brain lesions may be resected in some protocol settings. Routine liver and adrenal gland scanning is similarly controversial. Bone scans do not appear to be useful in patients with NSCLC unless they have clinical signs, symptoms, or laboratory findings to indicate possible metastases. Although heavily affected by local practice, radiologic evaluation of the patient with NSCLC should attempt to provide accurate determination of local disease and a search for distant metastases. PMID- 7781410 TI - Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer. AB - The contemporary surgical repertoire for the evaluation and treatment of patients with lung cancer includes the bronchoscope, mediastinoscope, thoracoscope, and standard surgical instrumentation. The recent advances in video optics and the development of endoscopic instruments have significantly expanded the surgical options for patients with lung cancer. Thoracoscopy, or the more inclusive term of video-assisted thoracic surgery (VATS), has been characterized as "minimally invasive" surgery. Thoracoscopy and VATS have decreased operative trauma and facilitated surgical staging prior to neoadjuvant therapy. An ancillary benefit to diminished surgical morbidity is shorter hospital stays with a concomitant reduction in costs to the patient and health-care system. These advantages make VATS ideal for elderly patients or patients with significant comorbidity. PMID- 7781412 TI - Benefits of aggressive perioperative management in patients undergoing thoracotomy. AB - With lung resection remaining the cornerstone of curative therapy in patients with lung cancer, aggressive perioperative management continues to play a critical role. This review summarizes the most important factors in successful perioperative management. These include patient selection, with an emphasis on which patient variables and hemodynamic assessments are most useful in determining operability. Postoperative management, in particular, patient controlled analgesia, and pulmonary toilet, are essential to facilitate early patient mobility and to minimize complications, respectively. Aggressive perioperative management can result in reduced postoperative morbidity and mortality, reduced length of hospital stay and expenditures for complications, and it expands the population that can receive potentially curative therapy. PMID- 7781411 TI - New chemotherapeutic agents for non-small cell lung cancer. AB - The identification of new chemotherapeutic agents for the treatment of non-small cell lung cancer should proceed in a structured, logical fashion. Agents should be evaluated on the basis of multiple objective and subjective end points. A 15% or greater major objective response rate, demonstrated in multiple single-agent phase II trials, is considered the lower limit for an agent to be deemed clinically active in this disease. A number of drugs previously have been identified in this category, including cisplatin, ifosfamide, mitomycin, paclitaxel, and the vinca alkaloids vinblastine and vindesine. Most of these conventional agents have been explored alone, in a variety of doses and schedules, and in combination. In the last several years clinical development has produced new agents, including chloroquinoxaline sulfonamide, docetaxel, edatrexate, gemcitabine, irinotecan, topotecan, and vinorelbine, which hold promise for more successful treatment of this lethal disease. PMID- 7781413 TI - Chemoprevention of lung cancer. AB - Treatment of lung cancer remains frustrating. Most patients with lung cancer are not candidates for curative therapy, and new therapies have not made a substantial impact on survival. Consequently, some clinical investigators have focused their efforts on developing prevention strategies. Chemoprevention, the administration of agents to block or reverse carcinogenesis, is being investigated in ongoing trials. Studies of chemoprevention in lung cancer have included trials to reverse premalignant lesions such as sputum atypia or squamous metaplasia of the bronchial epithelium. Clinical trials of lung cancer prevention have often studied groups of participants with tobacco or asbestos exposure. Other clinical trials are being conducted among patients who have been treated for an early-stage lung cancer. As the result of diffuse epithelial injury, these patients are at very high risk for developing second primary tumors, predominantly in the lungs and upper aerodigestive tract. It is our hope that these studies may establish a new strategy for preventing lung cancer. PMID- 7781414 TI - Pulmonary metastasectomy. Current indications. AB - Surgical resection remains an important form of treatment for pulmonary metastases from a variety of solid tumors. The most significant factors in selecting patients for operation include control of the primary tumor, ability to resect all metastatic disease, absence of extrathoracic metastases, lack of better alternative systemic therapy, and sufficient cardiopulmonary reserve for the planned resection. A solitary pulmonary nodule and long tumor doubling times and disease-free intervals usually define patients who experience better long term survival after pulmonary resection but do not constitute absolute criteria by which to select such patients. Complete surgical resection is critical to achieving long-term survival and is best accomplished via a standard or "clamshell" thoracotomy or a median sternotomy. The decision to proceed with the surgical resection of pulmonary metastases should be a multidisciplinary one, made jointly by the thoracic surgeon and the medical oncologist. PMID- 7781415 TI - Current approach to malignant mesothelioma of the pleura. AB - Malignant mesothelioma of the pleura occurs primarily in individuals who were exposed to asbestos either in the workplace or home. The incidence of malignant mesothelioma is rising and, reflective of the malignancy's long latency period, is expected to continue to increase into the next century. Current treatment measures, including surgery, radiation therapy, chemotherapy, intrapleural therapy, and combined-modality therapies, have had varying impacts on survival. This paper explores current trends in the treatment of malignant pleural mesothelioma. PMID- 7781416 TI - Mesothelioma and radical multimodality therapy: who benefits? AB - The incidence of malignant pleural mesothelioma is increasing. Untreated, patients with this disease experience a rapid and horrendous clinical decline. Surgery plays a role in the diagnosis, staging, and treatment of this malignancy. Surgery, chemotherapy, and radiotherapy alone have been unable to achieve major improvements in survival for most patients. More recent phase II trials suggest that surgery, at one time a purely palliative approach, may have a potentially curative role when used in combination with chemotherapy and radiotherapy. PMID- 7781417 TI - [Surgical treatment of traumatic cataract]. AB - 140 cases and 142 eyes with traumatic cataracts treated by extracapsular cataract extraction (ECCE), ECCE and intraocular lens implantation (ECCE + IOL), and lensectomy were reported. The data showed that postoperative corrected visual acuities > or = 0.1-1.0 were in 89 eyes (70%) in one week and in 33 eyes of 44 eyes (75%) followed up for more than 6 months. The 3 methods of operation were compared, the indications and the optimum time of operation for each method and the personal experiences of the authors in the operation were discussed. PMID- 7781418 TI - [An investigation on therapeutic results of extracapsular cataract extraction and intraocular lens implantation in diabetics]. AB - 44 cases (50 eyes) with diabetes and cataract were followed up for 6-30 months after extracapsular cataract extraction (ECCE) with intraocular lens implantation (IOL). No severe intra- and post-operative complications were found and 84% of eyes obtained post-operative corrected visual acuities > or = 0.5. The results suggest that the pre-operative hyperglycemia alone be not a contraindication of the operation. Pre-operatively, if the diabetes of patients with cataract can be controlled by diet or hypoglycemic agent, their glucose level in the blood remains normal and stable for a period of time and there are no other systemic and ocular complications, ECCE with IOL can be performed on such patients and the therapeutic results of the operation can be safe and reliable. PMID- 7781419 TI - [Gonioscopic observation after posterior chamber intraocular lens implantation]. AB - 6 months after senile extra-capsular cataract extraction and posterior chamber intraocular lens (IOL) implantation, Goldmann gonioscopy was performed on 30 eyes having undertaken the surgery. Peripheral anterior synechiae (PAS) were found in 17 eyes (56%). PAS overlying the positions of 20 lens haptics were observed in 15 eyes. It is easier to develop PAS in eyes with vertically fixed haptics than in eyes with horizontally fixed ones. The causes and the consequences of PAS were discussed. It is suggested that during the follow-up, routine gonioscopic observation after posterior chamber IOL implantation be necessary. PMID- 7781420 TI - [A comparison study of various anterior capsulectomies]. AB - The incidences of anterior capsular radial tears occurring in different capsulectomies performed on rabbit eyes under standardized conditions were compared. The eyes were randomly divided into 4 technique groups: (1) can opener, (2) capsulopuncture, (3) linear capsulotomy and (4) continuous circular capsulorhexis (CCC). The results demonstrated that the CCC technique has more advantages in comparison with other three groups. With the nuclear expression technique used in this study, no radial tears occurred with the CCC technique, whereas radial tears occurred in 100% of cases treated with other three techniques. PMID- 7781421 TI - [A real-time analysis of 133 normal lens images by a computer]. AB - According to the theory that the light scattering of the lens is correlated with the lens density, we designed a computerized system for the real-time analysis of the lens image. By measurement of the gray scale value of the lens optical section, the lens density is measured objectively and numerically. With the help of the system, 133 normal lens images were investigated. From the analysis of various age groups, we found that the grey scale values of the anterior cortex, posterior cortex and nucleus increase with the increase of age (P < 0.01), the grey scale values of the anterior and posterior cortex are significantly higher than the value of the nucleus (P < 0.05), but there is no significant difference between the values of the anterior and posterior cortex (P > 0.05), and there is also no significant difference in the comparisons of the grey scale values of the respective corresponding lens areas between the male and female. PMID- 7781422 TI - Nonaccommodative factors of refractive accommodative esotropia. AB - The clinical characteristics of 45 cases of refractive accommodative esotropia were compared with 31 cases of the control group who remained orthotropic in the presence of uncorrected same degree of hypermetropia. In addition to the general ophthalmologic and orthoptic examinations, the accommodative convergence/accommodation (AC/A) ratio, fusional vergences and random dot stereopsis were investigated. The hypermetropic patients without esotropia were found to have a lower AC/A ratio and normal fusional function, while in cases with refractive accommodative esotropia, their AC/A ratios were normal and their fusional functions were decreased, especially significant being the divergent fusional function. In both groups, their stereopsis was defective or absent. It is suggested that esotropia be not simply caused by excessive accommodation due to uncorrected hypermetropia, and the range of divergent fusional function and the level of AC/A ratio be the two factors which determine the causation of esotropia in cases with uncorrected hypermetropia. PMID- 7781423 TI - [Silicone oil removal in 31 cases]. AB - Silicone oil removal was performed on 32 eyes of 31 cases after silicone oil injection for an average of 13.9 months. The reasons for the silicone oil removal are the complications such as cataract, glaucoma, emulsification of the silicone oil and so on. Complete retinal reattachment without any complications was found in 6 eyes of the 32 cases. Retinal reattachment remained in place in 24 eyes after the removal, and 24 eyes achieved postoperative visual acuities > or = 0.02. After the removal, in 7 of 8 eyes with complication, retinal detachment reoccurred. The significance and the timing of the silicone oil removal were discussed in this paper. PMID- 7781424 TI - [An analysis of causes of post-operative shallow anterior chamber in glaucoma filtering surgery]. AB - 131 eyes of 103 cases having undertaken glaucoma filtering surgeries were randomly selected to analyze retrospectively the causes of the post-operative shallow anterior chamber. The causes are choroidal detachment accounting for 75.6%, excessive filtration 13.3% and malignant glaucoma 11.1%. As the rate of discovery of the choroidal detachment under a direct ophthalmoscope was quite low, the definite diagnosis depended primarily on B-ultrasonography. It is discovered that in the analysis of the possible factors leading to choroidal detachment, the plasma level of fibronectin is correlated to the development of the post-operative choroidal detachment of a glaucoma filtering operation, suggesting the impairment of microcirculatory function be investigated to approach the causes of the choroidal detachment following anti-glaucoma and other intraocular surgeries. PMID- 7781425 TI - [Studies on red blood cell-mediated immunity of patients with recurrent stromal herpes simplex keratitis]. AB - Assays of red blood cell (RBC) C3b receptor rosette and RBC immune complex (IC) rosette of 67 cases with recurrent stromal herpes simplex keratitis (HSK) were carried out. The results show that the rosette rate of RBC C3b receptor is markedly lowered and that of RBC IC receptor is significantly increased in cases with stromal HSK. In comparisons with the corresponding rates in the control group, there are significant differences (P < 0.01). The roles of RBC-mediated immunity in the immunopathogenesis of HSK were preliminarily discussed. PMID- 7781426 TI - [An observation on pathological changes in retinal ultrastructure of rat with hypertension and after its life-long treatment with captopril]. AB - The fundus and retinal ultrastructural changes of rats with hypertension and such rats having taken life-long captopril treatment were examined by funduscope, light and transmission electron microscopes. The normal rats were the controls. The results showed that in the hypertension group, the ratio of the diameter of the retinal artery to that of the vein was 1:2, the arteries were spastic and narrowed, their light reflexes were widened and their calibers of the lumens were uneven, the fundus appearances being consistent with grade I and II retinal changes of systemic hypertension. Under the light microscope, it was discovered that the basement membranes of the retinal capillaries were thickened and their lumens narrowed, resulting in retinal ischemia and anoxia. Under the transmission electron microscope, the main pathological changes involved the external segments of photoreceptors and ganglionic cells. The pathological changes were hazy renewed membranous discs at the basal portions of the external segments of photoreceptors, edematous ganglionic cells being the majority, their cytoplasm stained pale, mitochondrial vacuolization, enlargement of smooth endoplasmic reticula and degranulation of rough endoplasmic reticula. In the group of rats with hypertension having taken life-long captopril treatment, the fundi and blood pressure remained normal and no significant ultrastructural changes had taken place in their retinae. PMID- 7781427 TI - [A morphological study of experimental corneal neovascularization]. AB - Corneal neovascularization (CNV) was induced by alkali burn injuries in 20 rabbit corneas. The process of CNV was observed with biomicroscopy in vivo and histologically by light and electron microscopy. At 8 hours after injury, an obvious acute inflammatory response as evidenced by infiltration of neutrophils had already occurred in the pericorneal limbal area. Many neutrophils in the extravascular space contained abundant intracytoplasmic phagolysosomes. The vascular sprouts appeared 2 days after injury. The infiltration of neutrophils and their debris were visible around newly formed blood vessels in the cornea. The results suggest that there be the participation and an inductive action of neutrophils in the pathogenesis of CNV. PMID- 7781428 TI - YAG laser resection for the membrane on anterior surface of intraocular lenses. AB - The results and methods of YAG laser resection for the membrane forming postoperatively on the anterior surface of intraocular lens (IOL) in 33 eyes (31 cases) were reported. A monomode single pulse YAG laser was used to do a circular incision along the pupilar margin and blow it up. A multimode defocus burst was used to peel off the shrunk flap from the lens surface. The membrane in 27 eyes (81.8%) was completely removed in the first resection. The mean burst number was 49.2 +/- 26.3. The average energy of each burst was 1.3 mJ and the average total energy of each treatment was 62.1 +/- 37.1 mJ. Except 3 eyes with little blood oozing from iris near the pupilar margin, 4 eyes having foggy spots on IOL surface and 2 eyes with mild transient increased intraocular pressure (IOP) after resection, there were no other complications. The resection is safe and effective, could be instead of the second operation for unabsorbable organized membranes or the membrane causing blockage glaucoma, could accelerate the recovery of visual acuity and shorten or substitute medical treatment for thick membranes. PMID- 7781429 TI - [Observations on damage and regeneration of corneal nerves of rabbit eyes with herpes simplex keratitis]. AB - An experimental study on the damage and regeneration of the corneal sensory nerves in rabbit eyes with herpes simplex keratitis (HSK) was carried out by means of acetylcholine esterase staining and transmission electron microscopy. The results indicate that the diminution of the corneal sensitivity detected clinically in HSK is caused by the damage of the terminals of the sensory nerve plexus in the epithelial and subepithelial layers of the cornea and in the later stage of HSK, the corneal sensory nerves begin to regenerate, that is the basis of the restoration of corneal sensitivity. PMID- 7781432 TI - Clinical comparison of extracorporeal piezoelectric lithotripsy (EPL) and intracorporeal electrohydraulic lithotripsy (EHL) in difficult bile duct stones. A prospective randomized trial. AB - Today, nearly 90% of common bile duct stones are extracted endoscopically. Problems are encountered if there are large stones or a duct stenosis. Extracorporeal piezoelectric lithotripsy (EPL) as well as intracorporeal electrohydraulic lithotripsy (EHL) serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed. A total of 35 patients with common bile duct stones in whom conventional endoscopic treatment had failed were selected on the condition that stone visualization through ultrasound was possible and that the papilla was within easy reach of the endoscope. Patients fulfilling the inclusion criteria were randomly treated either by EPL or EHL. The average age of our patients was 73 years. The main reasons for failure of conventional endoscopy were due to the large size of the stones (13 patients), impacted stones (16), or the presence of a biliary stricture (6). In the EPL group, visualization of the stones by ultrasound and ensuing treatment were possible in 16 of 18 patients (89%); stones could be fragmented in 15 patients. In 13 patients, the biliary tree could then be completely freed of calculi; the success rate was 72% for all the patients (13 of 18). On average, the patients had 2.3 treatments on the lithotripter, and 3870 shock waves were applied per treatment. In the EHL group stones were successfully fragmented in 13 of 17 patients (76.5%). The average number of treatments was 1.4. Comparing both therapies, there was no difference in stone-free rates. In both groups, additional endoscopic interventions were necessary to clear the bile duct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781431 TI - Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones. AB - In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities < 100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5 +/- 11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones < 20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P = 0.0567) and in group II from 6.5 ml to 20.2 ml (P = 0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781430 TI - Correlation between biliary alpha 1-acid glycoprotein concentration and cholesterol crystal nucleation time in gallstone disease. AB - A biliary form of the alpha 1-acid glycoprotein (AAG) promotes cholesterol crystallization in the lower-molecular-weight, concanavalin A-bound fraction of gallbladder bile. In addition, bile AAG concentration is higher in cholesterol gallstone patients with multiple stones than in control patients without gallstone disease. In this study we sought to determine whether the increased biliary concentration of AAG in cholesterol gallstone patients is accompanied by a more rapid nucleation time in patients with multiple stones. AAG concentration in native biles was measured by ELISA. Nucleation time was measured using a standard microscopy method. The concentration of biliary AAG was then related to nucleation time in biles from the same patients. Nucleation times were significantly shorter (< or = 5 days) in cholesterol gallstone patients with raised AAG concentrations (P < 0.03). There was a significant (P = 0.004) negative correlation (r = -0.53) between nucleation time and the AAG concentration in cholesterol gallstone patients with multiple stones. The concentration of biliary AAG appears to exert an important influence on the speed of cholesterol nucleation in bile in many patients with cholesterol gallstone disease. PMID- 7781433 TI - Conjugated bile salts regulate turnover of rat intestinal brush border membrane hydrolases. AB - The mechanisms whereby the conjugated bile salts regulate the activities of the brush border membrane hydrolases and its physiological significance were investigated in rat small intestine, and comparisons were made with the action of pancreatic protease. Rat brush border membrane proteins were metabolically labeled with [35S]methionine, and isolated brush border membrane was incubated with taurocholate or pancreatic elastase. The activity of solubilized hydrolases was assayed and the molecular forms of the hydrolases were examined by SDS-PAGE. The activity and protein bands of alkaline phosphatase and sucrase-isomaltase were solubilized by taurocholate, while alkaline phosphatase was not solubilized by elastase. Solubilized sucrase-isomaltase molecules were proteolytically degraded by elastase, whereas the intact molecule of sucrase-isomaltase was solubilized by taurocholate. Next the physiological role of bile salts in brush border membrane hydrolase turnover were investigated using metabolic labeling of brush border membrane hydrolase and immunoprecipitation in biliary diversion rats. After three days of biliary diversion, a significant increase in alkaline phosphatase activity was observed. Although synthesis of alkaline phosphatase in biliary diversion rats was similar to that observed in control rats, biliary diversion rats showed 1.5-fold slower turnover of alkaline phosphatase when compared with control rats. These results suggest that conjugated bile salts in the intestinal lumen may cause a rapid turnover of brush border membrane hydrolases, which may be increased by the enhanced enzyme degradation. The mechanisms for the enhanced degradation appeared to be solubilization of hydrolases caused by the detergent activity of bile salts. Therefore, conjugated bile salts may play an important physiological role in the regulation of expression of the protease-resistant enzymes such as alkaline phosphatase. PMID- 7781434 TI - Comparative effects of secretin (SEC) and cholecystokinin-octapeptide (CCK-8) on pancreatic microcirculation. AB - Using epifluorescent microscopy, we investigated the dynamic changes in pancreatic microcirculation in vivo after bolus administration of secretin (SEC) (0.1-10.0 micrograms/100 g body wt) and cholecystokinin-octapeptide (CCK-8) (0.005-1.2 micrograms/100 g body wt) in pentobarbital-anesthetized rats. Pancreatic capillary red cell velocity as a monitor for pancreatic capillary blood flow was measured in 1-min intervals from 2 min prior to 8 min following bolus infusion of SEC or CCK-8. Physiological concentrations of SEC did not increase pancreatic capillary blood flow. However, pharmacological SEC concentrations induced a dose-dependent increase in pancreatic capillary blood flow (to 162 +/- 19% of baseline; P < 0.05), due to an increase in blood flow velocity (to 153 +/- 18% of baseline; P < 0.05). In contrast, bolus administration of physiological CCK-8 concentrations, which have been proven to stimulate enzyme secretion, induced a transient and dose-dependent increase in pancreatic capillary blood flow (to 235 +/- 24% of baseline; P < 0.05), due to an increase in blood flow velocity (to 184 +/- 13% of baseline; P < 0.05) and capillary diameters (+0.63 +/- 0.15 micron; P < 0.05). PMID- 7781435 TI - Occurrence of antibody against rat hepatic sinusoidal endothelial cells in sera of patients with autoimmune hepatitis. AB - To determine whether an antibody against hepatic sinusoidal endothelial cells was present in sera of patients with autoimmune hepatitis (AIH) type 1, we measured the serum IgG bound to the glutaraldehyde-fixed cultured rat sinusoidal endothelial cells by enzyme-linked immunosorbent assay. IgG bound to the cells was detected significantly more in patients with autoimmune hepatitis type 1 (97.1%) than in those with primary biliary cirrhosis (13.0%), chronic hepatitis C (5.9%) or B (7.9%), or healthy controls (0%). IgG-F(ab')2 fragments from autoimmune hepatitis patients also bound to the cells, and this binding was observed after absorption of the fragments with rat hepatoma cells, but not after absorption with bovine carotid endothelial cells. Culture of sinusoidal endothelial cells in the presence of IgG from AIH patients significantly reduced the number of viable attached cells. In conclusion, anti-sinusoidal endothelial cell antibody occurred in the sera from patients with autoimmune hepatitis type 1. PMID- 7781436 TI - A role for chronic hepatitis C virus infection in a patient with cutaneous vasculitis, cryoglobulinemia, and chronic liver disease. Effective therapy with interferon-alpha. AB - A six-year history of repeated attacks of fatigue, fever, arthralgias, skin changes, Raynaud's phenomenon, and neuropathy is reported in a patient with chronic liver disease. The following diagnoses were made: (1) leukocytoclastic vasculitis; (2) acute urticaria; (3) cryoglobulinemia type II with Raynaud's phenomenon and low serum level of C4; (4) peripheral polyneuropathy; (5) sicca syndrome; and (6) chronic hepatitis C virus infection. Despite therapy with corticosteroids symptoms increased gradually over years. In the first PCR of the nested PCR analysis, HCV-RNA was exclusively detected in the cryoglobulin fraction but not in the serum supernatant, suggesting that antibodies bind HCV particles, forming circulating immune complexes. As diagnoses 1-5 are well-known organ manifestations of cryoglobulinemia, we speculated whether treatment of hepatitis C with IFN-alpha (3 million IU IFN-alpha 2b three times a week) would inhibit HCV replication, decrease the cryocrit level and thereby ameliorate organ manifestations such as neuropathy and vasculitis. During treatment with IFN-alpha only a very weak or no signal could be detected for HCV-RNA in the cryoglobulin fraction as well as in the serum supernatant. This held true also for the serum supernatant in the second PCR. In parallel, cryoglobulin level, immunoglobulins, and liver enzymes decreased substantially to normal or near normal levels. Clinical symptoms-leukocytoclastic vasculitis and neuropathy-disappeared. We conclude that chronic HCV infection is involved in the pathogenesis of cryoglobulinemia and that IFN-alpha might be an effective treatment in these patients. PMID- 7781438 TI - Treatment of chronically draining infected echinococcal cyst with repeated injection of 96% ethanol. PMID- 7781437 TI - Exacerbation of primary biliary cirrhosis during interferon-alpha 2b therapy for chronic active hepatitis C. AB - A 60-year-old woman with chronic active hepatitis C was treated with 6 million units of rIFN-alpha 2b daily for two weeks and subsequently three times weekly for several months. Histological examination proved a severe form of chronic active hepatitis C unexpectedly complicated with primary biliary cirrhosis (PBC). Before treatment, levels of serum alkaline phosphatase (ALP) or gammaglutamyltranspeptidase (GGT) had remained within normal limits over six months, although anti-mitochondrial antibody (AMA) was shown to be positive. After eight weeks of therapy, the daily dose of rIFN was reduced to 3 million units because of a marked increase of ALP and GGT, although the serum alanine aminotransferase (ALT) was normalized. Four months later, IFN treatment was suspended because of continuous elevation of the ALP and GGT levels, and administration of ursodeoxycholic acid was substituted. Two months later, the ALP and GGT levels returned to the normal range, although ALT was not normalized and HCV-RNA remained positive. This is the first report case that demonstrates IFN treatment potentially exacerbates PBC associated with chronic active hepatitis C. It is important for treating physicians to keep this association in mind. PMID- 7781439 TI - Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases. AB - The term "autoimmune cholangitis" is used for a disease with clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative anti mitochondrial antibody (AMA) and positive anti-nuclear antibody (ANA) tests. In order to characterize autoimmune cholangitis and to determine whether this truly differs from PBC, we reviewed 200 cases morphologically consistent with PBC in which data on AMA and ANA status were available to us. Of these, 64 (32%) had a negative AMA, 114 (57%) had a positive ANA, and 40 (20%) had negative AMA and positive ANA (autoimmune cholangitis). The AMA-negative group was slightly younger on average (50 vs 55 years) than AMA positives (P < 0.05). There were no significant differences in gender (15.5% male overall), hepatic histopathology, or other laboratory tests between the groups of patients with any of the 4 possible combinations of AMA and ANA. Since the only consistently distinguishing feature among these patients is the autoantibody (AMA and ANA) profile, and they otherwise have virtually identical clinical and histopathologic features, autoimmune cholangitis can be considered to be the same as AMA-negative PBC. PMID- 7781440 TI - Suprahepatic vein oxygen tension in alcoholics with severe and mild liver damage. AB - We measured suprahepatic vein and arterial partial oxygen pressure in 35 alcoholics with severe (N = 7) or mild (N = 28) histological liver damage and without evidence of clinical liver failure. The suprahepatic vein was punctured with a fine needle, using a percutaneous approach. Suprahepatic vein partial oxygen pressure was lower and arterial-suprahepatic gradient higher in alcoholics with severe liver damage compared to those with mild damage (35.1 +/- 1.7 vs 44.1 +/- 2.1 and 58.9 +/- 3.7 vs 45.9 +/- 2.4 mm Hg, respectively; P < 0.001). Suprahepatic puncture was well tolerated and devoid of complications. It is concluded that alcoholics with severe liver damage have lower oxygen tensions in the suprahepatic vein, a phenomenon that supports the hypoxic theory of alcoholic liver disease. PMID- 7781441 TI - Hepatic blood flow during reduced liver grafting in pigs. A comparison of controls and recipients of intact allografts. AB - Intraoperative changes in portal venous and hepatic arterial flow were compared in porcine recipients of reduced liver grafts with recipients of intact grafts and sham-operated controls. Control animals showed no significant changes in hepatic blood flow (measured with perivascular ultrasonic cuffs), heart rate, mean arterial pressure, cardiac output, acid/base balance, plasma sodium, potassium, glucose, or catecholamines. Recipients of intact or reduced grafts showed hypotension, reduced cardiac output, tachycardia, and increased systemic vascular resistance during the anhepatic phase, which lasted approximately 30 min. These changes returned to normal in recipients of intact grafts but in recipients of reduced grafts, levels returned only to 50-60% of baseline. After intact grafting, total liver blood flow and the portal and arterial components returned to baseline within 2 hr of revascularization, but after reduced grafting, hepatic arterial flow values remained depressed to 50-60% of baseline. Plasma epinephrine and norepinephrine were unaltered during control operation but increased 4- to 20-fold in recipients of all grafts. These returned towards baseline in all except recipients of reduced grafts, in which norepinephrine levels remained significantly elevated for the 4 hr of postoperative study. These data highlight persistent elevation of plasma norepinephrine after reduced liver grafting, which may have contributed to the diminished hepatic arterial flow. These results need to be confirmed in adult recipients of split liver grafts in whom grafts are comparatively small. In such patients receiving donor livers which have undergone prolonged storage, the effects of increased plasma norepinephrine levels upon donor agonal arterial spasm may be significant. PMID- 7781443 TI - Fatal Vibrio parahemolyticus septicemia in a patient with cirrhosis. A case report and review of the literature. AB - Vibrio parahemolyticus has been well documented to cause outbreaks of infectious diarrhea, usually related to poor food handling; only rarely has it been reported to cause fetal septicemia. In contrast, Vibrio vulnificus is a well-known cause of septicemia, especially in patients with cirrhosis. A 31-year-old woman with cirrhosis who developed fatal V. parahemolyticus sepsis after ingesting raw seafood is described. We review the clinical syndromes associated with sepsis caused by these two organisms. Leg pain and bullous skin lesions may be a clue to the diagnosis. Febrile patients with cirrhosis should be questioned regarding recent seafood ingestion, and appropriate antibiotics chosen if this history is obtained. Physicians should inform patients at risk to avoid raw seafood in an attempt to prevent this potentially lethal syndrome. PMID- 7781442 TI - Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. AB - A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid. PMID- 7781444 TI - Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy. AB - Laser-induced autofluorescence has been used to discriminate normal from adenomatous colonic mucosa. However, few studies to date have studied the origin of colonic autofluorescence. Using confocal microscopy (excitation wavelength 488 nm), we have shown that autofluorescence at this wavelength is present predominantly in the lamina propria of normal mucosa but in the epithelium in adenomatous and hyperplastic polyps. The intensity ratio of epithelial cell to lamina propria fluorescence was significantly lower (P < 0.0001) in normal mucosa (0.52 +/- 0.01) compared with either adenomatous (1.6 +/- 0.2) or hyperplastic polyps (1.7 +/- 0.15). However, the ratios were not significantly different between hyperplastic and adenomatous polyps. Thus, confocal microscopy enables the detection of the sites of autofluorescence within colonic mucosa and the quantitation of differences in fluorescence between different tissue types. PMID- 7781445 TI - Urinary N1-acetylspermidine and N8-acetylspermidine excretion in normal humans and in patients with colorectal cancer. AB - Urinary N1-acetylspermidine (N1SPD) and N8-acetylspermidine (N8SPD) were measured in 24-hr urine specimens from 42 patients with colon adenocarcinoma and 29 healthy controls to assess their use as markers for colon cancer screening. Serial spot urines in four controls demonstrated significant fluctuations in these polyamine levels throughout the day without a distinct circadian pattern and therefore all subsequent analyses were performed on 24-hr collections. Both N1SPD and N8SPD were significantly increased in colon cancer patients compared to controls. Neither test correlated with tumor stage or location, but N8SPD was elevated in patients with poorly differentiated adenocarcinoma when compared to moderate or well-differentiated tumors. Using receiver operator characteristic (ROC) analysis, N1SPD had a higher information content than N8SPD, N1SPD + N8SPD, or the ratio of N1SPD/N8SPD and at a normal cut-off value of 4.0 nmol/mg creatinine, yielded a 95% specificity and 50% sensitivity for colon cancer. PMID- 7781446 TI - Fundic argyrophil carcinoid tumor in a patient with sporadic-type Zollinger Ellison syndrome. AB - In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors occur almost exclusively in the small subgroup of patients who also have multiple endocrine neoplasia type 1. In these patients, tumor development seems related to the same genetic alterations as those observed in other endocrine tumors related to multiple endocrine neoplasia type 1. We report here the second detailed case of a patient with sporadic Zollinger-Ellison syndrome who developed an argyrophil carcinoid tumor in nonatrophic fundic mucosa, suggesting that chronic hypergastrinemia may lead to fundic carcinoid development in nongenetically predisposed patients. PMID- 7781447 TI - Malignant schwannoma of the liver. AB - Malignant schwannoma is the most common soft tissue sarcoma in adults, but primary schwannoma of the liver is extremely rare. We report an autopsy case of malignant schwannoma of the liver in a 63-year-old man. The tumor involved almost the entire right lobe of the liver. Microscopically, it was composed of moderately pleomorphic spindle cells with hyperchromatic nuclei with mitotic figures. The spindle cells were stained positively with antibodies to both S-100 protein and vimentin. Necrosis was found in the primary tumor. Only four other cases of malignant schwannoma of the liver were found in a review of the literature. Pertinent features of these tumors are discussed. PMID- 7781448 TI - Prospective evaluation of gastrointestinal tract in patients with iron-deficiency anemia. AB - Gastrointestinal bleeding is believed to cause iron-deficiency anemia (IDA). The information concerning ideal evaluation of the gastrointestinal tract and exact findings in patients with IDA is scant. The aim of this study was to prospectively evaluate patients with IDA for gastrointestinal lesions potentially causing IDA at a US Army Teaching Medical Center with Gastroenterology Fellowship. Seventy patients with IDA had esophagogastroduodenoscopy (EGD) and colonoscopy, and if this evaluation was unremarkable, then small bowel biopsy was obtained at EGD to evaluate for celiac disease. Enteroclysis was done if endoscopic evaluation was negative. At endoscopy, at least one lesion potentially accounted for the IDA in 50 (71%) patients. At colonoscopy, 21 (30%) patients had 22 lesions (four colon cancer, seven adenoma > 1 cm, six vascular malformation, four severely bleeding hemorrhoids, one ileal Crohn's); at EGD, 39 (56%) patients had 43 lesions (11 gastric erosion, 10 esophagitis, four vascular malformation, four celiac disease, three gastric cancer, three gastric ulcer, three duodenal ulcer, two gastric polyp > 1 cm, one duodenal lymphoma, one esophageal cancer, and one duodenal Crohn's). Twelve (17%) patients had both upper and lower gastrointestinal tract lesions. Twenty-four of 32 (75%) patients with positive fecal occult blood test had potentially bleeding lesions compared to 24 of 38 (63%) patients with negative fecal occult blood test (P > 0.05). Six of nine patients with malignancy had positive fecal occult blood test. Twenty patients with normal endoscopy and small bowel biopsy had normal enteroclysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781449 TI - Hydrogen peroxide injury to the colon. PMID- 7781450 TI - Free radical scavengers prevent reflux esophagitis in rats. AB - Free radical damage in reflux esophagitis of rats induced by 24-hr duodenojejunal ligation was studied. Oxygen free radicals were selectively blocked. Groups were: sham operation, reflux, reflux + superoxide dismutase (SOD), catalase, dimethylthiourea, allopurinol, and inactivated SOD or inactivated catalase alone or in the combination SOD + catalase or SOD + catalase + dimethylthiourea + allopurinol. Macroscopic esophagitis was inhibited only by SOD, alone or in combination with other agents. Esophageal mucosal lipid peroxidation was 10-fold increased in the reflux group compared to the sham group (P < 0.05). This response was damped by SOD > catalase (P < 0.05) but not by the inactivated enzymes, dimethylthiourea or allopurinol. SOD + catalase showed no significant improvement on SOD alone. Total inhibition of lipid peroxidation was achieved by combining all scavengers. Total glutathione (GSH) in the esophageal mucosa was stimulated by reflux. This response was inhibited by scavengers equivalent to their efficacy in preventing lipid peroxidation. It is concluded that reflux esophagitis is associated with free radical release with O2- being the main source. Free radicals appear to stimulate GSH production in this prolonged oxidative stress. PMID- 7781451 TI - Esophagitis in Sprague-Dawley rats is mediated by free radicals. AB - Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration. PMID- 7781452 TI - Active oxygen species in formation of acute gastric mucosal lesions induced by thermal injury in rats. AB - Active oxygen species generated by circulating leukocytes and released from the gastric mucosa were measured in the process of acute gastric mucosal lesion formation after thermal injury in rats. Alterations of luminol-dependent chemiluminescence activities generated by leukocytes obtained from the gastric vein and the inferior vena cava were approximately same. A decrease in chemiluminescence activity 15 min after thermal injury and a significant increase in chemiluminescence activity 5 hr after thermal injury were observed in leukocytes from both veins. From 15 min to 12 hr after thermal injury, luciferin dependent chemiluminescence activities were significantly higher than that of the control group. Oral administration of rebamipide resulted in decreased mucosal lesion formation. Rebamipide, an antiulcer agent that protects the mucosa from damage in various animal models decreased chemiluminescence activities only released from the gastric mucosa but not from circulating leukocytes. These results suggest that two different pathways of active oxygen species formation may exist in the pathogenesis of acute gastric mucosal lesions after thermal injury. PMID- 7781453 TI - Velocity of peristaltic propagation in distal esophageal segments. AB - Recent studies of the peristaltic pressure wave have suggested the presence of two sequential but overlapping contraction segments in the distal esophageal body. In this report, propagation velocity of esophageal peristalsis was determined in these segments in normal subjects (N = 35) and in patients with high-amplitude peristalsis (nutcracker esophagus, N = 25) to see if intersegment differences were present in the normal or abnormal setting. Velocity measurements were made from conventional manometric tracings in two 4-cm regions representing the distal smooth-muscle segments. A novel method of velocity measurement was employed that used regression lines established from contraction onset times. In normal subjects, propagation velocity decreased significantly from the proximal to distal segment (4.9 +/- 0.5 cm/sec, vs 3.2 +/- 0.2 cm/sec, P < 0.01). Velocity also decreased across segments in nutcracker-esophagus patients (5.3 +/- 0.6 cm/sec, vs 3.6 +/- 0.7 cm/sec, P = 0.06), but the difference reached statistical significance only when the subset with highest amplitudes (> or = 180 mm Hg) was analyzed separately. Greater variance in velocity in the distal smooth-muscle segment of nutcracker-esophagus patients (P < 0.01) was, in part, responsible for this statistical observation. We conclude that normal propagation velocity decreases across regions corresponding to the smooth-muscle contraction segments defined by recent studies of peristalsis, supporting the assumption that they represent separate neuromuscular units. The mechanisms responsible for contraction wave abnormalities in the nutcracker esophagus have a minimal effect on propagation velocity, an effect that is restricted to the distal smooth-muscle segment of the esophageal body. PMID- 7781454 TI - How well can quantitative 24-hour intraesophageal pH monitoring distinguish various degrees of reflux disease? AB - Twenty-four normal subjects and 64 symptomatic patients with various degrees of reflux disease (24 with reflux symptoms without esophagitis and 21 with mild and 19 with severe esophagitis) underwent quantitative 24-hr intraesophageal pH monitoring. Various reflux parameters during supine, interprandial, and postprandial periods were examined by binary logistic regression and by CART analysis to determine the sensitivity and specificity to separate the various groups of subjects and patients. The distinction was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100% by logistic regression and 95% and 88%, respectively, by CART), but discrimination was poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71% and 79% by logistic regression and 75% and 92% by CART), which is the most important indication for pH recording in clinical practice. A 3-hr postprandial pH recording was inadequate to distinguish the various groups. The acidity of the reflux episodes during the night appeared to be a crucial factor in the development of severe erosive esophagitis. The duration of esophageal acid exposure was another important factor in the development of reflux lesions. PMID- 7781455 TI - Increasing pain sensation to repeated esophageal balloon distension in patients with chest pain of undetermined etiology. AB - Previous studies have demonstrated lowered sensory thresholds to esophageal balloon distension in patients with chest pain of undetermined etiology. Whether this finding is specific to patients with chest pain or is simply related to an underlying esophageal motility disorder is unclear. In the present study, distension-induced pain-sensation scores and the effect of repeated balloon distension were compared in patients with chest pain, dysphagia secondary to esophageal dysmotility, and healthy controls. All subjects underwent standard esophageal manometry followed by mid-esophageal balloon distension. Volumes 2.5, 5, 7.5, and 10 ml (each volume repeated three times) were applied in random order in a single-blind fashion, and the pain-sensation score was recorded after each distension. Pain-sensation scores varied directly with balloon volume. Mean pain scores were significantly higher (P < 0.001) in the chest pain group than in either the controls or dysphagia group. There was no significant difference between controls and the dysphagia group, and the motor response to distension was no different between groups. In the controls and dysphagia groups, pain sensation score was not significantly different between the first, second, or third distension at a given volume. However, in the chest pain group, pain sensation scores increased significantly with the second (P = 0.004) or third (P = 0.002) distension using the same balloon volume. These studies suggest that abnormal esophageal nociception in patients with chest pain of undetermined etiology is not simply related to underlying esophageal motor dysfunction. In addition, chest pain patients display a conditioning phenomenon, further supporting the presence of a visceral sensory abnormality. PMID- 7781456 TI - Mechanism of Helicobacter pylori-associated gastric mucosal injury. AB - Helicobacter pylori infection is associated with gastric mucosal damage and the infiltration of neutrophils. Myeloperoxidase from neutrophils produces hypochlorous acid, which yields monochloramine in the presence of ammonia produced by urease enzyme of Helicobacter pylori. The target cells of gastric mucosal damage are gastric mucosal cells and endothelial cells. We therefore tested the hypothesis that ammonium, hypochlorous acid, and monochloramine damage the target cells. We studied the in vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and activated neutrophils on the target cells. Cytotoxicity was measured by a 51Cr-release assay. Ammonium chloride, sodium hypochlorite, and monochloramine were toxic to labeled cells in a concentration dependent manner. The toxicity of these agents was in the order monochloramine > sodium hypochlorite >> ammonium chloride. Incubation of labeled cells with activated neutrophils, Helicobacter pylori, and urea resulted in cytolysis. These cytotoxicities were significantly inhibited by the scavenger of hypochlorous acid, taurine. Monochloramine is more toxic to the target cells than ammonium chloride. Although ammonium chloride at neutral pH by itself has little direct damaging effect on the gastric mucosa, it is damaging to the gastric mucosa through a reaction with hypochlorous acid, suggesting that it plays a role in Helicobacter pylori-associated gastric damage. PMID- 7781457 TI - Zinc deficiency delays gastric ulcer healing in rats. AB - Zinc is an important element in wound healing. Zinc compounds hasten the healing of gastric ulcers, by an unknown mechanism(s). We studied the effect of the induction of zinc deficiency on gastric ulcer healing. Rats were given a control or zinc-deficient diet for six weeks and then subjected to the induction of acetic acid-induced chronic gastric ulcers. Four days later, zinc-deficient rats were divided into two groups. In the first group, the zinc-deficient diet was continued. In the second group, the diet was changed to the control diet. Zinc deficient rats had a mean serum zinc concentration approximately 70% of that in controls. Zinc deficiency did not affect the formation of gastric ulcers; however, it reduced cell proliferation by day 4 and delayed ulcer healing. Zinc supplementation brought zinc to control levels within a week, but failed to reverse the delay in ulcer healing. We conclude that zinc is crucial for healing of gastric ulcers, especially at the early stage. PMID- 7781459 TI - Time course of mucosal cell proliferation following acute aspirin injury in rat stomach. AB - The time course of replicating cell proliferation in the gastric fundic mucosa following acute aspirin-induced injury was determined by BrdU labeling. Gastric erosions were produced in adult rats by gastric gavage using aspirin (200 mg/kg) suspended in 0.15 M HCl. Lesion scores indicated significant gross injury in the aspirin-treated rats at all times measured (from 2 to 48 hr). BrdU labeling was not elevated at 2 or 8 hr after gavage. A significant increase in labeling was observed at 15 hr, reached a maximum at 16 hr, and declined with a slight, but significant increase still present at 48 hr. Elevations in BrdU labeling were uniform and seen in areas adjacent to and distant from the gross injury. The BrdU labeling in the fasted control rats decreased during this same time period. The height of the proliferative zone was not altered from control in the aspirin treated rats despite the marked differences in proliferation activity. This study demonstrates the importance of the time course in the assessment of mucosal cell proliferation following injury. PMID- 7781460 TI - In vitro recovery of canine gastric mucosal surface hydrophobicity and potential difference after aspirin damage. AB - This study determined how the luminal surface hydrophobicity and transmucosal potential difference (PD) of canine gastric mucosa changed during the recovery period after the tissue was challenged with acidified aspirin. Luminal aspirin reduced both the contact angle and PD of mucosae incubated in Ussing chambers. After the removal of aspirin, surface hydrophobicity was found to recover before PD, and nutrient 16,16-dimethyl prostaglandin E2 accelerated the recovery of both parameters. Restoration of luminal surface hydrophobicity may be an important component of how the stomach reestablishes its barrier properties after exposure to a luminal damaging agent. PMID- 7781458 TI - Nonsteroidal antiinflammatory drugs and dyspepsia in the elderly. AB - Upper gastrointestinal tract symptoms are common in the elderly and, despite a paucity of data, nonsteroidal antiinflammatory drugs (NSAIDs) are believed to be important risk factors. We aimed to evaluate the association of NSAIDs with dyspepsia and heartburn in a population-based study. An age- and gender stratified random sample of Olmsted County, Minnesota, Caucasian residents aged 65 years and older was mailed a valid self-report questionnaire; 74% responded (N = 1375). Age- and gender-adjusted (to 1980 US Caucasian population) prevalence rates for NSAID use, dyspepsia (defined as pain located in the upper abdomen or nausea), and heartburn (defined as retrosternal burning pain) were calculated. Logistic regression analysis was used to estimate the association of dyspepsia and heartburn with potential risk factors adjusting for age and gender. The age- and gender-adjusted annual prevalences (per 100) of aspirin and nonaspirin NSAID use were 60.0 (95% CI 57.2, 62.7) and 26.1 (95% CI 23.6, 28.7), respectively. The annual prevalences of dyspepsia and heartburn were 15.0 (95% CI 12.9, 17.0) and 12.9 (95% CI 10.9, 14.8), respectively. Aspirin was associated with dyspepsia and/or heartburn (OR = 1.6, 95% CI 1.2, 2.2) as were nonaspirin NSAIDs (OR = 1.8, 95% CI 1.3, 2.6), but smoking and alcohol were not significant risk factors. Aspirin and nonaspirin NSAIDs are associated with almost a twofold risk of upper gastrointestinal tract symptoms in elderly community subjects. PMID- 7781461 TI - A double-blind study of pantoprazole and ranitidine in treatment of acute duodenal ulcer. A multicenter trial. European Pantoprazole Study Group. AB - Pantoprazole is a new substituted benzimidazole, which is a potent inhibitor of gastric acid secretion by its inhibition of H+,K(+)-ATPase. Pantoprazole, 40 mg, was compared with the H2-receptor antagonist ranitidine, 300 mg, in the healing of acute duodenal ulcer. Two hundred seventy-six patients with endoscopically diagnosed duodenal ulcer were studied in this multicenter double-blind study. Patients were reendoscopied after two weeks of treatment, and those patients whose ulcers remained unhealed were also endoscoped after an additional two weeks of treatment. The primary end point was the complete healing of the ulcer. Demographic characteristics were comparable in both treatment groups. After two weeks of treatment, 90/124 (73%) patients in the pantoprazole group had healed ulcers compared with 57/126 (45%) patients in the ranitidine group (P < 0.001, per-protocol analysis). After four weeks, the cumulative healing rates were 92% and 84% in the pantoprazole and ranitidine groups, respectively (P = 0.073). Symptoms were also improved at week 2, with 84% and 72% of patients in the pantoprazole and ranitidine groups, respectively, reporting no ulcer pain (P < 0.05, per-protocol analysis). Both treatments were well tolerated. This study has confirmed the superiority of pantoprazole compared with ranitidine in the healing of duodenal ulcers and pain relief after two weeks of treatment and has shown pantoprazole to be well tolerated in this indication. PMID- 7781462 TI - L-arginine/nitric oxide pathway modulates gastric motility and gallbladder emptying induced by erythromycin and liquid meal in humans. AB - There is recent evidence that nitric oxide, a soluble gas produced from L arginine, is released by the smooth muscle cells and neurons of the gastrointestinal tract where it exerts a myorelaxive action. However, little is known about the effects nitric oxide has on gastric and gallbladder motility during the inter- and postprandial phases in man. We therefore investigated the effects 200 mg/kg/hr L-arginine exerts on the gastric and gallbladder motility induced by 2 mg/kg erythromycin or a liquid meal in 21 subjects in a double blind, placebo-controlled study. Gastric and gallbladder emptying were evaluated by sonography. Fasting antral motility was expressed as antral motility index (MI). In fasting subjects, L-arginine administration determined a threefold increase in plasma nitrite concentrations. Administration of erythromycin caused a significant rise in the antral MI, which was inhibited by L-arginine (P < 0.05). Ingestion of a liquid meal also significantly increased antral MI, but it returned to basal values 90 min after the end of the meal. Although L-arginine administration caused a significant reduction in the antral MI (P < 0.05), it did not inhibit gastric emptying. L-Arginine provoked an approximately 40% increase in basal gallbladder volume, completely blocked erythromycin-induced emptying, and partially, but significantly, prevented the emptying induced by a liquid meal (P < 0.01). Our study suggests that nitric oxide may be implicated in the physiological modulation of gastric and gallbladder motility during the inter- and postprandial phases in man. PMID- 7781463 TI - Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate. AB - Treatment with short-chain fatty acids (SCFAs) seems promising in ulcerative colitis and changes in colonocyte oxidation of butyrate have been suggested to be of importance for the development of this disease. The influence of small and large bowel length after surgery on SCFAs is only partly known. SCFAs and lactate were measured in consecutive fecal samples from 300 patients with ulcerative colitis (103), Crohn's disease (127), and noninflammatory bowel disease (70); 205 had had surgery, 52 had short bowels (< 200 cm). Lactate (mainly the L-isomer) was elevated in ulcerative colitis patients with pancolitis (mean +/- SEM, 17 +/- 5 mmol/liter) and proctitis (12 +/- 3 mmol/liter) compared with quiescent ulcerative colitis (3 +/- 1 mmol/liter, P < 0.01), and correlated with the index of Truelove (R = 0.52, P < 0.0005). Lactate was also increased in Crohn's colitis (21 +/- 8 mmol/liter), but not in isolated ileitis (4 +/- 2 mmol/liter), compared with quiescent Crohn's disease (7 +/- 2 mmol/liter, P < 0.02), but did not correlate with the activity index (CDAI; R = 0.18, P = 0.12). In contrast to earlier reports, SCFAs (including butyrate) did not correlate with inflammatory activity or localization in either ulcerative colitis or Crohn's disease. The length of the small bowel had no influence on SCFAs and lactate in patients with either no colonic function (ileostomies), or with > 50% and < 50% preserved colorectal length, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781464 TI - Response to intraluminal gas in irritable bowel syndrome. Motility versus perception. AB - Our aim was to evaluate the response to intraluminal gas in irritable bowel syndrome and to determine whether this response was consequent upon disordered motility or altered perception. We evaluated 10 patients who satisfied the clinical criteria for the diagnosis of irritable bowel syndrome and 10 healthy controls. An eight-lumen perfused catheter assembly was positioned to monitor motor activity in the duodenum and proximal jejunum; a separate side port in the distal duodenum permitted gas infusion. Subjects recorded symptoms of abdominal pain, bloating, and nausea throughout the study, using a visual analog scale. Following an overnight fast and a 60-min basal recording period in the fasted state, subjects ate a standard meal; 60 min later, "sham" gas was administered for 20 min, followed by the actual infusion of nitrogen gas at 40 ml/min. Subjects were randomized to receive atropine (7 micrograms/kg) or placebo intravenously during the period of actual gas infusion. Patients with irritable bowel syndrome described more pain (score, mean +/- SE, control versus irritable bowel: 0.22 +/- 0.16 vs 1.65 +/- 0.5, P < 0.01) and nausea (0.25 +/- 0.21 vs 1.45 +/- 0.64, P < 0.04) during sham gas; motility indices were similar in both groups. During active gas, irritable bowel syndrome patients reported more pain (0.40 +/- 0.39 vs 2.94 +/- 1.16, P < 0.03); motility indices at all sites were similar in both groups. Symptom severity in irritable bowel syndrome subjects randomized to receive atropine was similar to control subjects during active gas infusion; motility indices were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781466 TI - Crohn's disease and factitious physical disorders. PMID- 7781465 TI - Functional and morphological changes in small bowel of Crohn's disease patients. Influence of site of disease. AB - Morphological and functional changes were examined in the upper jejunum and terminal ileum of 18 patients suffering from Crohn's disease. Intestinal permeability, biochemical determination of enzymatic activities, and morphologic evaluation of the severity of the lesions were evaluated. Ulcerative colitis and irritable bowel syndrome patients served as controls. We found abnormal lactulose mannitol tests in all patients with active Crohn's disease. Permeability changes correlated with increased crypt cell proliferation, as indicated by thymidine kinase activity. A significant reduction in brush border enzyme activities was seen in the terminal ileum, but no significant change was observed in the unaffected upper jejunum. The number of mast cells was increased in the diseased ileum. We conclude that the site of inflammation and the healing capacity of the epithelium are important in determining functional and biochemical abnormalities in active Crohn's disease. Changes may be dependent on the type and number of immune cells involved in the inflammatory process. PMID- 7781467 TI - Severe thrombotic complications in a postpartum patient with active Crohn's disease resulting in ischemic spinal cord injury. AB - This report describes a 33-year-old female patient who presented with severe neurological symptoms and signs during postpartum relapse of Crohn's ileocolitis. The cause of the neurological deficit was extensive major vessel thrombosis resulting in spinal cord ischemia. Etiologic factors involved in this exceptional thrombotic state are discussed with emphasis on the relationship between low levels of folic acid, homocysteine metabolism, and coagulation. PMID- 7781468 TI - Collagenous colitis. A treatable disease with an elusive diagnosis. AB - Collagenous colitis is associated with normal endoscopy examination and peculiar histopathological changes. The natural history and optimal treatment are not well defined. Our objectives were to analyze the symptomatology of collagenous colitis, determine the natural history, and response to treatment. All patients with collagenous colitis from 1978 to 1992 were studied. Demographic data, symptomatology, associated conditions, colonoscopic findings, and pathology specimens were reviewed. Clinical improvement was classified as none, partial, or complete. Nineteen patients were identified, mainly white females over age 50. Mean follow-up was 22.6 months. Symptom duration was 37 months (range 4 months to 15 years). Symptoms were intermittent diarrhea (19), with a predominant nocturnal component (13); abdominal pain (15); and mild weight loss and incontinence (8). Colonoscopy was normal in 12 patients. Segmental mucosal edema and loss of vasculature pattern were present in seven. Antiperistaltic agents were used in 17 patients with no improvement (15), partial resolution (1), and complete resolution (1). Eight nonresponders received sulfasalazine. Responses were none (6) or complete (2). Ten patients received steroids (10-20 mg/day). One failed to respond. Nine initially responded completely but two relapsed. Seven patients who did not respond to any type of treatment improved eventually, two partially and five completely. These patients were younger (54.3 vs 68.3 years, P = 0.04) and symptom duration was shorter (25.4 vs 44.5 months, P = 0.38) than the rest of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781470 TI - Idiopathic perforation of sigmoid colon. PMID- 7781469 TI - Placebo controlled study randomizing leuprolide acetate. PMID- 7781471 TI - Cold versus warm cardioplegia: recognizing hemodynamic variations. AB - The use of warm blood cardioplegia during open-heart surgical procedures represents a marked departure from the traditional hypothermic approach used over the past 30 years. Current literature regarding the two techniques reveals interesting and sometimes confusing results. Nurses aware of the different hemodynamic responses from both techniques provide critical assessment skills, which help prevent or identify early complications for these patients. PMID- 7781472 TI - Caring for patients with acute myocardial ischaemia: the perhexiline maleate experience. AB - Perhexiline Maleate (Px) is a potent, oxygen-sparing agent used in the management of patients with acute myocardial ischaemia that is resistant to conventional pharmacological therapy. The critical care nurse plays an integral role in (1) maximizing the therapeutic benefits of Px and (2) ensuring that the patient reaches the point of correctional intervention with the minimum of ischaemic damage. PMID- 7781474 TI - Intravenous patient-controlled analgesia in critically ill postoperative/trauma patients: research-based practice recommendations. AB - PCA use is increasingly common in the Intensive Care Unit. The authors review current PCA research and make recommendations for the optimal use of PCA in the critically ill patient. PMID- 7781473 TI - Examining management of pain for infants following cardiothoracic surgery. AB - Pain management for infants continues to be inadequate despite evidence that infants do experience pain. Some health professionals fear that the risks of administering medication for pain outweigh the benefits. In caring for infants thought to be in pain, nurses often choose to administer a minimal dosage of analgesia; administer a sedative for its calming effects; or try to maximize relief by combining the analgesics and sedatives prescribed. Findings from this study indicate that the administration of analgesics and sedatives to relieve pain or calm an infant may be too conservative. PMID- 7781475 TI - "Preventing complications of PEG tubes". PMID- 7781476 TI - Escorting the family out of the ICU: ethical and legal issues. AB - This article presents an interesting case where nurses touched a family member to escort her out of the ICU against her wishes. In the case analysis, the nurse attorney author reviews the ethical and legal issues in this case. PMID- 7781477 TI - Battered women in the critical care setting: strategies for critical care nurses. AB - Nursing intervention with battered women can be a frustrating and discouraging experience, as battered women are trapped in a cycle of violence that is difficult to break. Research reveals an Open Window Phase within the cycle of violence. During this brief period, battered women are most receptive to interventions. The responsibility of the critical care nurse to intervene during this short period of time is particularly urgent. This article provides intervention strategies for nurses in critical care to use during the Open Window Phase. PMID- 7781478 TI - Morphological and pathogenetic aspects of proliferative vitreo-retinopathy. A histological and immunohistochemical study. AB - Proliferative vitreo-retinopathy (PVR) and subretinal membrane proliferation are the most common complication and cause of failure in retinal-detachment (RD) surgery. In this study, material withdrawn from 21 patients was observed. The vitreal taps of 16 bulbs affected by PVR and which had undergone vitrectomy, along with 5 bulbs obtained by enucleation, were stained with Hematoxylin Eosin and studied immunohistochemically. The cells involved in this proliferative tissue include macrophages, cellular elements of pigmented epithelium origin, fibroblasts and myofibroblasts. From the examination of enucleated bulbs, we can easily recognize that the cellular components of the membrane are represented by fibroblasts, capillaries, and occasional macrophages; meanwhile, PE cells remain at the base of the newly formed tissue. PMID- 7781479 TI - Morphometrical analysis of retinal arterial macroaneurysms. AB - Twenty-one macroaneurysms and related vessels of 19 patients were evaluated morphometrically. Macroaneurysms were classified into two groups as hemorrhagic and exudative in terms of their major clinical sign. Average diameters of the macroaneurysms were arranged in a Gaussian distribution curve (mean and standard deviation: 281.60 +/- 57.28 micrometers). Regarding the distribution curve based on this data macroaneurysm can be defined as being greater than 109.76 micrometers. Macroaneurysms were most frequent on the superotemporal vessels (52.38%), followed by the inferotemporal (38.10%), inferonasal (4.76%) and superonasal vessels. Average diameter (r = +0.68, p = 0.0006) and area (r = +0.71, p = 0.0003) of the macroaneurysms were significantly correlated to the diameter of the relevant arterial segments. The distribution of the macroaneurysms in respect to arterial bifurcation (chi 2 = 18.762, p = 0.0003) and arteriovenous crossings (chi 2 = 8.286, p = 0.0405) were nonrandom with macroaneurysms clustering near this points. Hemorrhagic macroaneurysms were significantly closer to the optic disc (p < 0.01) and were located on relatively larger arterioles (p < 0.01). They were also more circular (p < 0.01) in shape and greater in area (p < 0.01) and diameter (p < 0.01) than the exudative ones. These findings suggest that the location of the macroaneurysm is closely related to its clinical appearance. PMID- 7781480 TI - Influence of existing retinal correspondence on the results of squint operations in alternating convergent strabism. AB - In our study we examined the influence of existing retinal correspondence on the result of squint operations for alternating convergent strabism. 157 patients under 10 years of age at the time of their first or only operation were included. They were divided into groups, depending on their age at the onset of squint and subgroups according to their type of retinal correspondence. The development of distance and near deviation was investigated separately. Covariance analysis demonstrated that the preoperative sensorial state is a predictor for the motor outcome of surgery with regard to postoperative distance deviation. Statistically we found at least noticeable results (p < 0.15) in all groups of patients--for acquired esotropia a significant result (p < 0.01). With regard to the postoperative near deviation we found a significant influence of the preoperative sensorial state only in the group of patients with a late onset of squint (p = 0.05). For patients with an earlier onset (before the 30th month) of strabismus, the preoperative angle of near deviation proved to have a significant impact on the postoperative development of near deviation (p < 0.05). Sensorio-motorial adaptational phenomena in esotropia are presumed to be the major cause for this difference. PMID- 7781482 TI - Secondary hyperfunction of unoperated inferior oblique muscle after surgical treatment of strabismus. AB - Secondary hyperfunction of the inferior oblique muscle IO of one of the eyes is a frequent complication after unilateral recession of the overacting IO of the fellow's eye. It is often observed in cases with bilateral asymmetric hyperfunction of the IO's when these are surgically decreased. The pathogenesis of this secondary hyperfunction is not sufficiently explained yet. We evaluated the condition of unoperated IO in 42 children with unilateral hyperfunction of the IO. In all cases the operation we performed was recession combined with a fixed anteroposition. During the two years follow up period we found no secondary hyperfunction of the unoperated oblique muscle in 31 of the children, mild level of elevation in 7 of them, middle--in 2, and severe in 2 of the children. This observation confirmed our conviction of refraining from simultaneous surgical intervention on both IO muscles when there is hyperfunction of one of them. PMID- 7781481 TI - Fornix- vs. limbus-based flaps in combined phacoemulsification and trabeculectomy. AB - We studied prospectively the results of limbus-versus fornix-based flaps in patients undergoing combined trabeculectomy and phacoemulsification. We found no significant difference at six months postoperatively in the level of intraocular pressure between the limbus-(16.1 +/- 4.1 mm Hg) and fornix- (14.0 +/- 3.4 mm Hg, p = 0.161) based groups, or in the number of glaucoma medications (p = 0.0750). The highest intraocular pressure recorded within the first postoperative month was similar between groups (18.4 +/- 6.9 mm Hg for limbus and 18.5 +/- 5.5 mm Hg for fornix, p > 0.900). Postoperative bleb height, extent, and vascularity, as well as chamber depth were statistically similar between groups (p > 0.05). Postoperative complications were similar between groups. This study indicates that both fornix- and limbus-based flaps may be used safely and effectively when performing a trabeculectomy combined with phacoemulsification. PMID- 7781483 TI - The cytological, immunocytochemical and molecular genetic analysis in diagnosis of the neoplasms of the eye, eye adnexa and orbit. AB - The fine needle aspiration biopsy was performed in 91 patients including 57 cases of retrobulbar tumors done under CT control. All aspirates were cytologically examined. In 21 cases immunocytochemical examination was performed in order to distinguish poorly differentiated neoplasms. In 19 cases malignant lymphoma was distinguished from pseudolymphoma. Cytological diagnosis was confirmed by histopathological examination in 77 cases /84%/. One result was false positive, 3 false negative. The value of immunocytochemical methods in differential diagnosis of poorly differentiated neoplasms was stressed. PMID- 7781484 TI - Spectral transmission of the optical media of the human eye with respect to keratitis and cataract formation. AB - The spectral transmissions of cornea, aqueous humour, lens and vitreous humour of human eyes were measured in the range from 250 nm to 800 nm in 1 nm steps using a high resolution double monochromator. Cornea and lens are good cut off filters; 1% transmission was measured in various cornea samples between 291 and 298 nm, and in different lenses between 389 and 414 nm. Aqueous humour and vitreous humour showed high transparency (80%) at lambda > 320 nm. The wavelength range of keratitis effective irradiance was found to be completely within the wavelength range of absorption of the cornea, that of cataract effective irradiance was found to be at the short wavelength end partly outside the wavelength range of absorption of the lens. It may therefore be supposed that the action spectrum of cataract obtained by animal experiments is applicable to the human eye only with certain reservations. PMID- 7781485 TI - Persistent choroidopathy in systemic lupus erythematosus. AB - We report a case of a rare entity, choroidopathy in association with systemic lupus erythematosus (SLE), previously described in only twelve patients to our knowledge. It manifested by multiple focal serous elevations of the sensory retina and/or serous detachments of the retinal pigment epithelium bilaterally. No retinal vascular changes were observed. The probable pathogenesis is related to choroidal vascular disease due to systemic hypertension secondary to lupus nephritis, vasculitis, or a combination of these. PMID- 7781486 TI - Macular drusen and the sensitivity of the central visual field. AB - Macular drusen are one of the earliest signs of age-related macular degeneration but little information is available on the functional aspects of macular area in patients with drusen. To determine if drusen are associated with changes in central visual field sensitivity, one eye of each of 35 subjects (mean age 64.9 years) with bilateral drusen and visual acuity of 1.0 (20/20) underwent automated static threshold perimetry of the central 10 degrees. 16 normal subjects (mean age 65.8 years) were used as controls. 30 degrees fundus photographs were graded in a masked fashion for the clinical characteristics of drusen: type, size and number. The mean sensitivity (MS) of the central 10 degrees was significantly lower in eyes with drusen compared to normal eyes (p = .0001). After grading drusen eyes for size (> or = 63 mu) and type (presence of soft drusen), MS significantly deteriorated when large and soft drusen were present. These results suggest that central visual field sensitivity is precociously affected in eyes with drusen and that testing central visual field sensitivity may be useful as functional parameter in long term studies on the evolution of age-related macular degeneration. PMID- 7781487 TI - Lubrithal (Leo viscous eye gel), precorneal residence time in normal and dry eyes. AB - In an open, right/left controlled study we compared the effects of topical carbomer gel Lubrithal (Leo viscous eye gel) and polyvinyl alcohol (Liquifilm, Allergan) in 20 patients with dry eyes and in 20 healthy subjects. The average precorneal residence time of carbomer gel in patients and healthy subjects was 92.8 min (+/- 35.7) and 36.5 min (+/- 14.2), respectively, while it was 40.8 min (+/- 19.4) and 19.5 min (+/- 8.3) in the polyvinyl alcohol group. The tear break up time was 10 min after instillation significantly longer with the carbomer gel: 23.0 seconds (+/- 5.5) in dry eye patients and 26.2 seconds (+/- 4.4) in healthy subjects compared to polyvinyl alcohol: 10.4 seconds (+/- 3.4) in dry eye patients and 16.5 seconds (+/- 7.1) in healthy subjects (p < 0.001). Seventy-five per cent of the dry eye patients preferred Lubrithal. PMID- 7781488 TI - Baroreflex function in streptozotocin (STZ) induced diabetic rats. AB - To determine whether the renal sympatho-inhibition and bradycardia in responses to acute increases in arterial pressure are altered in the diabetic state, the renal nerve discharge and heart rate were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Integrated renal sympathetic nerve activity and heart rate were measured before and during an acute increase in blood pressure in anesthetized (Inactin 0.1 g/kg, i.p.) control (vehicle) and DIA rats (Sprague Dawley rats injected with STZ 65 mg/kg i.p.). Blood glucose levels were significantly elevated in the DIA group compared with the control group. Baroreflex changes in renal nerve activity and heart rate were not significantly different in the DIA rats compared with control rats at a time when the renal sympatho-inhibition in response to acute volume expansion was blunted in the diabetic rats. In addition, blocking the effect of elevated angiotensin II in diabetic rats with the converting enzyme inhibitor enalapril did not change the baroreflex function in DIA rats compared with control rats. However, administration of vasopressin failed to potentiate the baroreflex in diabetic rats as it did in normal control rats. This study demonstrates that (1) the baroreflex function is normal in STZ induced diabetic rats unlike the volume reflex during the early phase of the disease, (2) blockade of the AII system does not alter baroreflex function in diabetic rats and (3) vasopressin fails to potentiate the baroreflex in diabetic rats as it does in the euglycemic normal rats. PMID- 7781489 TI - Ascorbic acid supplementation prevents hyperlipidemia and improves myocardial performance in streptozotocin-diabetic rats. AB - The present study investigated the effects of ascorbic acid (AA) supplementation on the cardiac performance and the plasma levels of glucose, insulin, triglycerides, cholesterol and free fatty acid in diabetic and non-diabetic rats. Diabetes was induced by intravenous injection of streptozotocin (STZ) 55 mg/kg. AA was given in drinking water in concentrations of 1 g/l or 2 g/l for 8 weeks after STZ injection. Myocardial performance was determined using the isolated perfused working heart preparations. Following AA supplementation, there were no significant changes in any of the parameters measured in non-diabetic rats; however, the occurrence of polydipsia, hyperphagia, hyperlipidemia and myocardial dysfunction in STZ-diabetic rats was significantly alleviated in a dose-dependent manner. Nevertheless, the decreased body weight gain, hypoinsulinemia and hyperglycemia in diabetic animals were not affected. The data show that AA supplementation in STZ-diabetic rats improves both hyperlipidemia and cardiac function. However, the mechanisms of these effects and the correlation between these improvements are not clear. PMID- 7781490 TI - Lack of effect of CS-045, a new antidiabetic agent, on insulin secretion in the remnant pancreas after 90% pancreatectomy in rats. AB - We assessed the effect of CS-045, a new hypoglycemic agent, on B-cell function in partially pancreatectomized rats. At the age of 4 weeks, male Wistar rats were subjected to 90% pancreatectomy (Px). For 2 weeks starting at 6 weeks after surgery the Px rats were treated with CS-045 (CS rats) mixed with chow pellets in a proportion of 0.2% (w/w). To compare the efficacy of CS-045 with that of insulin therapy, an osmotic pump was implanted to release insulin (1.2 units/day) into the intraperitoneal cavity of the Px rats (Is rats). Plasma glucose levels in the CS and Is rats were significantly lower than in the control Px rats; however, no marked improvement in plasma glucose or insulin levels was observed in glucose tolerance test (2 g/kg, i.p.) in the CS rats. Insulin secretion by the isolated perfused pancreas in response to 16.7 mM glucose showed a biphasic pattern, but was slightly reduced in the Px and CS rats compared with the Is rats. Insulin secretion induced by 19 mM arginine was unaffected by the treatment. The insulin content of the CS rats was significantly greater than in the Px and Is rats. Histological observations suggested regranulation of the pancreatic islets of the CS rats. B-cell areas within the islet were restored to normal levels in the Cs and Is rats. These findings indicate that the hypoglycemic effect of CS-045, which is not mediated by insulin secretion from the residual pancreas, prevents destruction of the islet. PMID- 7781491 TI - Stimulation of insulin secretion and potentiation of glibenclamide-induced insulin release by the dimethyl ester of glutamic acid in anaesthetized rats. AB - The dimethyl ester of L-glutamic acid (GME) stimulates insulin release in isolated pancreatic islets and may represent a novel experimental tool in the study of non-insulin-dependent diabetes. In the present study, GME was found both to stimulate insulin secretion and to augment glibenclamide-stimulated insulin release in normal anaesthetized rats. A comparable hierarchy in the magnitude of the secretory response to GME and/or glibenclamide was found in control rats and animals injected with streptozotocin during the neonatal period. In the latter animals, however, the B-cell secretory response was invariably lower than in control animals. It is proposed that GME represents a novel tool to bypass anomalies of glucose transport and metabolism in the beta cell and, hence, to stimulate insulin release and enhance the insulinotropic action of hypoglycaemic sulphonylurea in animal models of non-insulin-dependent diabetes. PMID- 7781493 TI - Serum concentrations of basement membrane proteins in NIDDM as a prognostic marker for nephropathy. AB - Metabolic changes of basement membrane proteins, collagenous and non-collagenous, will be followed by morphological changes and develop into diabetic microangiopathy. In this study, serum concentrations of laminin and type IV collagen were measured in 87 cases o f non-insulin-dependent diabetes mellitus (NIDDM) and examined with the development of diabetic nephropathy and retinopathy. Serum type IV collagen was measured by two methods, assays of the 7S portion (7S-RIA) and of both the 7S and central triple helical domain (IV-EIA). IV-EIA showed more significant elevation with development of diabetic microangiopathy than 7S-RIA and laminin. After measurement of basement membrane proteins, 66 cases were followed clinically for 3 or 4 years. In 45 cases without worsening of diabetic nephropathy, IV-EIA and laminin concentrations in serum were significantly lower than those in 21 cases who showed worsening of diabetic nephropathy in the same period, Multivariate analysis revealed a good model including three dependent variables of serum values of laminin, IV-EIA and mean blood pressure for discriminating between the worsened group and the non-worsened group. High values of IV-EIA and laminin in serum may be useful in predicting the worsening of diabetic nephropathy. PMID- 7781492 TI - Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese -class II antigen and autoimmune thyroid disease. AB - HLA-DQA1 and DPB1 alleles were examined in relation to autoimmune thyroid disease (AITD) in the Japanese type 1 diabetic patients. The subjects consisted of 14 type 1 diabetic patients with Graves' disease, 12 patients with Hashimoto's thyroiditis and 32 type 1 diabetic patients without AITD. Comparisons were made with 35 normal controls. Among the type 1 diabetic patients with Graves' disease, the age at onset of diabetes was 31.8 +/- 14.6 years old, which was later than that of those without AITD (P < 0.01). DR9 was increased (57.1% vs. 25.9%, P < 0.05, RR: 3.85, chi 2:4.36) in the patients with Graves' disease. DQA1*0301 was increased and DQA1*0103 was decreased in the patients with Graves' disease and those without AITD. HLA-DPB1*0501 was increased (92.9% vs. 54.3%, P < 0.05, RR: 11.0, chi 2:6.57) in the patients with Graves' disease. These findings suggest the existence of a Graves' complicated subgroup characterized by the increasing association of DPB1*0501 and late onset of diabetes in Japanese type 1 diabetic patients. There exists a heterogeneity in Japanese type 1 diabetes. PMID- 7781494 TI - Effect of chronic vanadate administration in partially depancreatized rats. AB - The effects of vanadate on B-cell function and replication in rats after 90% partial pancreatectomy (Px) were compared with insulin therapy. At the age of 4 weeks, male Wistar rats were subjected to sham operation or Px. Vanadate (0.2 mg/ml) was given in drinking water for 3 weeks starting at 2 weeks after surgery. Regular insulin (2.4 units/day) was administered as a continuous subcutaneous infusion through an osmotic pump. Plasma glucose levels were significantly higher in the Px rats than in the sham rats from 1 week after surgery. Vanadate lowered plasma glucose levels to near normal values in the Px rats as early as 2 days. The effect was sustained throughout the experiment. The hypoglycemic effect of insulin was less than that of vanadate. During an i.p. glucose tolerance test, plasma glucose levels were decreased in the Px rats treated with vanadate or insulin, while plasma insulin levels were not affected. The insulin content in the Px rats treated with vanadate was significantly (P < 0.01) greater than in the insulin-treated Px rats. Histological examination showed fibrotic degeneration in the enlarged islets of Px rats, whereas the normal structure was retained in most islets of the Px rats treated with vanadate and insulin. In addition, B-cell areas within the islet were restored to normal levels not only in the insulin-treated Px rats but in the vanadate-treated Px rats. However, both vanadate and insulin failed to stimulate proliferative activity of the B-cells. These data suggest that vanadate is a new therapeutic option to ameliorate the diabetic state after Px. PMID- 7781495 TI - Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus. Hyogo Pravastatin Study Group. AB - This study reports the result of a 12-month, open-label multicenter study of the efficacy and tolerability of pravastatin in the management of hypercholesterolemia associated with non-insulin-dependent diabetes mellitus. Pravastatin produced a decrease, in 138 diabetic and 51 non-diabetic patients, in total serum cholesterol by 19 and 20%, in low-density lipoprotein (LDL) cholesterol by 25 and 29%, in apolipoprotein B by 15 and 19% and in triglycerides by 8 and 5%, respectively. High-density lipoprotein cholesterol levels were increased by 9% in both groups. All of these changes were significant (P < 0.001) except for triglycerides changes in non-diabetic patients, where the change was not significant and no significant differences were observed between the two groups. These favorable effects on LDL cholesterol and apolipoprotein B were not influenced by gender, the type of diabetic therapy, baseline hemoglobin A1c levels and by the presence of hypertension or gross proteinuria, although a decrease in the two variables were less in those with body mass index > or = 26.4 kg/m2 or in those with age < 60 years. Adverse experiences were similar between treatment groups and the drug was well tolerated. Only one diabetic patient was withdrawn from the study because of pruritus. Pravastatin produced no change in fasting plasma glucose concentrations and hemoglobin A1c levels in diabetic patients throughout the study. Pravastatin was generally effective in improving the serum lipids of hypercholesterolemic diabetic patients. PMID- 7781496 TI - Prevalence of hypertension and albuminuria in a teaching hospital diabetes clinic. AB - The prevalence of hypertension and its relationship to nephropathy were measured in a hospital-based diabetic clinic. Six hundred patients (300 insulin treated, 300 non-insulin treated) were randomly selected from a clinic population of 1054 insulin treated and 1039 non-insulin treated subjects. Eighty-three percent of patients with insulin treated diabetes and 72% of patients with non-insulin treated diabetes were studied. Blood pressure data from the Belfast MONICA project were used for the control group. In patients with insulin treated diabetes (age 25-64 years) the prevalence of a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or on treatment for hypertension (WHO criteria) was 19.1% in males (NS, vs. control group) and 17.8% in females (NS); the prevalence of a systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg was 17.6% in males (NS, vs. control group) and 9.5% in females (NS). In patients with non-insulin treated diabetes (age 35-65 years) the prevalence of hypertension by WHO criteria (see above) was 26.8% in males (NS, vs. control group) and 28.9% in females (NS); the prevalence of a systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg was 21.4% in males (NS, vs. control group) and 17.8% in females (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781497 TI - Mortality from coronary heart disease and cerebrovascular disease and associated risk factors in diabetic patients in Osaka District, Japan. AB - Mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD), as well as associated risk factors, were examined. The subjects studied were 1939 non-insulin-dependent diabetic (NIDDM) patients and 503 deaths were observed during a mean follow-up period of 9.4 years. Of these deaths, 62 were CHD deaths and 84 were CVD deaths. The mortality rates per 1000 person-years from CHD were 3.95 for males and 2.57 for females and those from CVD were 5.12 and 3.86 for males and females, respectively, showing a higher mortality for males and an increasing trend with age. The baseline factors associated with CHD mortality were age at entry into the study, hypertension, ischemic ECG changes, serum cholesterol level, diabetic retinopathy and albuminuria, while those associated with CVD were age at entry, hypertension, ischemic ECG changes, diabetic retinopathy, albuminuria and therapeutic regimen, all of which were found to be significant by univariate analysis. The relationships were further analyzed by the multiple logistic method. In addition, the baseline characteristics of the patients who died of CHD and CVD were compared with those of patients who died from other causes. The baseline characteristics in cases of deaths from CHD and CVD were significantly different from those of deaths from other causes in terms of obesity, ischemic ECG changes, serum cholesterol level and serum triglycerides level for deaths from CHD and in terms of age at onset, age at death and hypertension for deaths from CVD. PMID- 7781498 TI - [Stress reduction through listening to music: effects on stress hormones, hemodynamics and mental state in patients with arterial hypertension and in healthy persons]. AB - Stress hormones, tissue-plasminogen activator (t-PA) antigen, left-ventricular diastolic function and mood immediately before and after listening to three different kinds of music (a waltz by J. Strauss, a piece of modern classic by H. W. Henze, and meditative music by R. Shankar) were measured in 20 healthy persons (10 women, 10 men; mean age 25 [20-33] years) and 20 hypertensives (8 women, 12 men; mean age 57.5 [25-72] years). To recognise haemodynamic effects, mitral flow by Doppler ultrasound was used as a measure of left-ventricular diastolic function. Atrial filling pressure (AFF) was calculated from the flow integral (VTI) of the early E and the late A waves. The Zerssen scale was used to estimate the immediate mood of the subjects. In hypertensives the levels of cortisol (74 vs 78 ng/ml; P < 0.05) and t-PA antigen (4.3 vs 4.5 ng/ml; P < 0.05) were lower after than before the Strauss waltz. The muscle by Henze lowered the concentrations of cortisol (70 vs 84 ng/ml; P < 0.05), noradrenaline (203 vs 224 ng/l; P < 0.05) and t-PA antigen (4.1 vs 4.6 ng/ml; P < 0.05). After listening to the piece by Shankar the concentrations of cortisol (71 vs 78 ng/ml; P < 0.05), adrenaline 14.5 vs 24.5 ng/ml; P < 0.05) and t-PA antigen (4.2 vs 4.3 ng/ml; P < 0.05) were lower. In healthy subjects AFF (29 vs 26%; P < 0.05) rose after the Strauss music, VTI-E fell (69 vs 73 mm; P < 0.05, while natriuretic peptide rose (63 vs 60 pg/ml; P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781499 TI - [Tubulointerstitial nephritis-uveitis syndrome (TINU syndrome)]. AB - For 10 weeks a 25-year-old man had been suffering from tiredness, fatigue, nausea and a 16 kg weight loss. Erythrocyte sedimentation rate (83/133 mm), serum C reactive protein (5.5 mg/dl) and creatinine (5.05 mg/dl) were all elevated. He also had proteinuria (1120 mg daily), sterile leukocytosis and a creatinine clearance of 10 ml/min. Renal biopsy showed interstitial nephritis and bone marrow biopsy revealed non-caseous epithelioid-cell granulomas. 14 days after admission he developed acute iritis in the right eye. Other causes having been excluded, the diagnosis of tubulo-intestinal nephritis with uveitis (TINU syndrome) was made. The clinical symptoms and laboratory findings improved within a few days of the start of glucocorticoid treatment (initially, 100 mg prednisone daily, reduced to 5 mg within 30 days). The patient was discharged after 8 days in good general condition. PMID- 7781500 TI - [Differential diagnosis of commonplace upper abdominal symptoms: hepatic echinococcosis]. AB - A 17-year-old girl from Turkey had for 6 years been suffering from right-sided upper abdominal symptoms not usually related to food intake. Treatment of suspected gastritis remained ineffective. Laboratory tests were unremarkable, except for an accelerated erythrocyte sedimentation rate (12/30 mm), eosinophilia (6.4%) and albumin concentration of 52.6 g/l. Upper abdominal sonography revealed a cyst, about 10 cm in diameter, in the right liver lobe. Computed tomography showed the 8 x 8.5 cm cyst which was septated at its caudal portion and compressed the vena cava for 5.6 cm. The antibody titre against echinococcus antigen was 1:3200. At laparotomy the echinococcal cyst was found to have extended to the left adrenal gland, renal fat capsule and left part of the diaphragm. There was a pressure necrosis on the right lateral aspect of the vena cava. The affected parts were resected and the patient quickly recovered. Postoperative treatment consisted of the administration of mebendazole (1.5 g daily) for 18 months. The patient had come from an area where echinococcal infection is endemic. The disease could have been quickly and easily diagnosed and cured if sonography had been undertaken early, sparing the patient major surgery. PMID- 7781501 TI - [Substitution therapy with estrogens and gestagens]. PMID- 7781503 TI - [Postsplenectomy sepsis (overwhelming postsplenectomy infection (OPSI) syndrome)]. PMID- 7781502 TI - [Mesalazine]. PMID- 7781504 TI - [Primary immunization and booster vaccination against polio]. PMID- 7781505 TI - [Adjuvant therapy in colorectal carcinoma]. PMID- 7781506 TI - [Adjuvant therapy in colorectal carcinoma]. PMID- 7781507 TI - [Adjuvant therapy in colorectal carcinoma]. PMID- 7781508 TI - [Pyrimethamine-sulfadiazine resistant cerebral toxoplasmosis in AIDS]. PMID- 7781509 TI - [Nasal continuous positive airway pressure (nCPAP) therapy in obstructive sleep breathing disorders]. AB - The therapeutic efficacy and the incidence of significant side effects of nasal continuous positive airway pressure (nCPAP) treatment was investigated in 1140 patients with sleep-related apnoea (1089 men, 51 women; mean age 53.2 +/- 9.2 [16 84] years). All had been treated for the condition with nCPAP at the Marburg University Medical Polyclinic between 1986 and 1992. The mean number of attacks of apnoea and/or hypopnoea per hour of sleep ("respiratory disturbance index", RDI) was 45.8 +/- 25.6 before treatment and 3.5 +/- 4.8 under nCPAP. 21.1% of patients had an apnoea index of no more than 10/h. 11.6% an RDI of no more than 15/h. The average airway pressure was 8.7 (3-18) cm H2O. The treatment was successful in 1023 patients and these decided to continue the treatment long term. The RDI could not be lowered under 10/h in 63 patients, while 4 patients declined ambulant treatment despite the demonstrated efficacy of nCPAP. Three patients developed acute left ventricular failure in the initial phase of the treatment, while in another 16 patients long-persisting central hypoventilation was shown to occur. These data show that treatment with nCPAP can be employed for all degrees of severity of obstructive sleep apnoea. However, because of the potentially life-threatening side effects, the introduction of the treatment must be undertaken in the sleep laboratory under continuous monitoring. PMID- 7781510 TI - [The von Hippel-Lindau syndrome. Its differential diagnosis from cystic kidneys in adulthood]. AB - A 51-year-old patient with severe back pain had undergone resection of a benign cerebellar tumour when aged 15 years. In addition, polycystic kidney disease was diagnosed 24 years ago, bilateral phaeochromocytoma 2 years ago, and for 4 months before the present admission he had been on haemodialysis. The family history indicated autosomal dominant inheritance of the polycystic renal disease. His general condition was found to have deteriorated, he had pain on pressure over the upper thoracic and lower lumbar vertebrae, and the kidneys were enlarged on palpation. There were increased concentrations of calcium (3.01 mmol/l), parathormone (2.0 ng/l), carcinoembryonic antigen (13.5 micrograms/l) and TPA (69 U/l). Computed tomography demonstrated cystic and solid parts of much enlarged kidneys. Biopsy revealed a poorly differentiated clear-cell renal carcinoma. Further information concerning the previously removed brain tumour showed this to have been an haemangioblastoma of the cerebellar tonsils indicating the diagnosis of v. Hippel-Lindau disease. Nine other family members had been affected, but none had the full-blown picture of the disease. The patient died 3 weeks later from the rapidly advancing tumour. Autopsy showed the bilateral renal carcinoma, bilateral phaeochromocytoma and metastases to the sternum, femurs, vertebrae and liver. PMID- 7781511 TI - [Thrombosis of a prosthetic mitral valve in the anticardiolipin syndrome]. AB - A 40-year-old woman in whom the mitral valve had to be replaced with a prosthetic one (St. Jude's) had to be reoperated 8 months later because of endocarditis on the second prosthetic valve (Carbo-Medics). Four months later her general condition deteriorated progressively with cough and dyspnoea, requiring hospitalization. Auscultation revealed moist rales over both lung bases; heart sounds were distant but otherwise normal. The "international normalized ratio" was 2.5, while erythrocyte sedimentation rate, white cell count and C-reactive protein were normal. Transthoracic echocardiography demonstrated a hardly moving mitral valve prosthesis with an opening area of 0.8 cm. Subsequently this decreased further and measurement of the anticardiolipin antibody titre revealed an IgG fraction of 37.9 U/ml (normal up to 12 U/ml). Within 48 hours thrombolysis with streptokinase had increased the valve's opening area to 1.8 cm. The patient made an uneventful recovery under strict anticoagulation. This case illustrates that the anticardiolipin syndrome can be a cause of an otherwise unclear genesis. PMID- 7781512 TI - [Dermatoscopy. A new method for the clinical diagnosis of malignant melanoma]. PMID- 7781513 TI - [Nephropathy due to contrast media. Its pathogenesis and prevention]. PMID- 7781514 TI - [A plea for clinical pancreas transplantation]. PMID- 7781515 TI - [Bladder emptying disorder]. PMID- 7781517 TI - [Xanthogranulomatous pyelonephritis with phlegmonous abdominal wall infiltration]. PMID- 7781516 TI - [The therapy of Sjogren's syndrome]. PMID- 7781518 TI - [Unilateral femur amputation and infrarenal abdominal aortic aneurysm--the facts from the viewpoint of the biometrician]. PMID- 7781519 TI - [Pulmonary mucormycosis in an HIV-infected patient]. PMID- 7781520 TI - [Homeopathic drugs in airway infections in childhood]. PMID- 7781521 TI - [Vascular endothelial growth factor in the ocular fluid in diabetic retinopathy and other retinal diseases]. PMID- 7781523 TI - [Restriction enzyme mismatch polymerase chain reaction in the demonstration of Ki ras-oncogene mutation in carcinoma of the pancreas]. AB - A pilot study was undertaken to test whether combining the polymerase chain reaction with restriction fragment length polymorphism is suitable for the routine diagnosis of carcinoma of the pancreas. The method makes it possible to recognize point mutations in codon 12 of the Ki-ras oncogene. 60 cytological specimens from the pancreatobiliary tract, the bronchopulmonary system (by bronchoalveolar lavage or from pleural effusion) and ascites were tested. Results from nine pancreas carcinoma cell lines served as control. A PCR product was successfully amplified in all cell lines and 47 of the clinical specimens. In all eight samples in which a mutated Ki-ras oncogene was demonstrated, there was at least a suspicion of malignancy by cytological examination. A mutation was also found in four of five pancreas carcinomas. But no mutation was found in one, clinically certain, case of pancreas carcinoma. The described method is an elegant and, most of all, rapid means to complement and optimize any cytological diagnosis. PMID- 7781522 TI - [Ki-ras mutation as a molecular tumor marker for carcinoma of the pancreas]. AB - More than 90% of tumours of the pancreas have mutations on codon 12 of the Ki-ras oncogene. Cellular DNA from pancreatic secretions and fine-needle biopsies, obtained from 69 patients (41 men, 28 women), were amplified by the polymerase chain reaction (PCR) to demonstrate this characteristic marker. All these patients had undergone endoscopic retrograde pancreatography for suspected pancreatitis or carcinoma of the pancreas. Two different methods were developed to demonstrate the mutations. With the aid of one of these methods, enrichment PCR with analysis of the restriction fragment length (FL), mutations on codon 12 of the Ki-ras gene were demonstrated in unstimulated pancreatic secretions of 29 of 33 patients with pancreatic carcinoma. All eleven fine-needle biopsies that had been cytologically examined showed the tumour-specific mutation. After direct sequencing of enrichment PCR a codon 12 mutation was demonstrated in pancreatic secretion from 21 of 24 patients and with the single strand conformation polymorphism analysis in 17 of 33 patients. In two of these 33 patients two different Ki-ras mutations were discovered. No mutations were found in acute inflammations or stone disease, while in five patients with chronic pancreatitis mutations were demonstrated only in those two patients in whom histological examination had revealed precancerous mucinous hyperplasia. This investigation indicates that codon 12 mutations of the Ki-ras gene, found after PCR in pancreatic secretion and biopsies, constitute a sensitive and specific tumour marker whose clinical value is being assessed. PMID- 7781524 TI - [Ki-ras mutation--a specific and sensitive tumor marker for carcinoma of the pancreas?]. PMID- 7781525 TI - [Intra-aortic balloon counterpulsation as percutaneous therapy option in cardiogenic shock]. AB - Six months after sustaining a posterior wall myocardial infarction a 40-year-old man had a further infarction in the anterior wall region. After thrombolysis treatment with recombinant tissue plasminogen activator the patient was at first symptom-free and haemodynamically stable, but 48 hours later another anterior wall re-infarction occurred with cardiogenic shock. Despite infusions of catecholamines at highest dosage and successful coronary angioplasty the circulation became critically unstable and percutaneously introduced intraaortic balloon counterpulsation (IABCP) was commenced. As the haemodynamics improved catecholamine dosage was markedly reduced and then discontinued over the subsequent 24-48 hours and inspiratory oxygen concentration of the ventilated patient was decreased from 100% to 40%. After a total of 5 days the IABCP catheter was removed without complication. The cardiac pump action showed further improvement in the following days. 6 months later the patient's condition was stable in grade II-III (New York Heart Association classification) heart failure. This case illustrates the place of IABPC as a highly effective treatment option in myocardial infarction with cardiogenic shock, especially when combined with interventional revascularisation procedures. PMID- 7781527 TI - [Methods in medicine: computerized tomography]. PMID- 7781526 TI - [Urinary calculi analysis. Methods and relative value in the age of minimally invasive stone removal]. PMID- 7781529 TI - [Therapy of arterial hypertension and coronary heart disease in coexisting aortic valve stenosis]. PMID- 7781528 TI - [Intravascular ultrasonography in coronary heart disease. Current aspects in the pathogenesis]. PMID- 7781530 TI - [Antibiotic prophylaxis in indwelling catheter of the bladder?]. PMID- 7781532 TI - [Diagnosis of immune deficiency]. PMID- 7781531 TI - [Fibrinogen levels in ultra-high dosage streptokinase lysis]. PMID- 7781533 TI - [Continuous examination of sows with cystic, degenerating ovaries using sonography and serum hormone determination]. AB - Ten sows with cystic ovaries have been examined periodically by transrectal sonography (2 days intervals) and analysis of serum-progesterone and estradiol (7 days intervals). Estrus occurred in nine of the sows after a time up to 82 days. Estrus reappeared after an almost physiological interval of 22 to 24 days. The cysts on the ovaries regressed completely (4 sows) or diminished in size (5 sows) before estrus. The regression was preceded by increasing echoes from trabeculae like structures in the cysts and increase of serum progesterone concentration. In six sows cysts were again detectable after estrus. These increased in size and regressed again in the same manner as before. All nine sows were served by a boar during second estrus and seven became pregnant according to sonographic findings after 27 days. These results show that sows with cysts on there ovaries may maintain an ovarian cycle and even conceive. The regression of ovarian cysts is probably preceded by the formation of luteal tissue. Our results don't allow general conclusions concerning the role of ovarian cysts in sows as a cause of infertility due to the small number and the unknown anamnesis of our patients. However in only one of the ten sows, the cysts persistent beyond the observation time of 100 days. PMID- 7781534 TI - [The therapy of urinary tract infections in sows]. AB - Fifteen sows spontaneously infected with Eubacterium suis were treated with enrofloxacin and, if necessary, with ampicillin. Before and after treatment different blood and urine parameters were determined with regard to renal function and the condition of the urinary bladder was examined by cystoscopy. Besides results of a controlled treatment in a breeding herd with a high frequency of urinary tract infections are referred. Duration of treatment with appropriate dosage should be at least 10 days. Even when a haemorrhagic inflammation was present therapy of infections with Eubacterium suis showed no problems, if the alterations were restricted to the bladder. In sows with renal insufficiency in case of ascending infection treatment is also possible on principle, but intensive infusion therapy is necessary in addition to antibiosis. Reliable estimation of the renal function can be obtained by measurement of creatinine and urea blood levels. Enrofloxacin treatment of urinary tract infections was successful in a breeding herd. An insufficient water supply and a high incidence of crystalluria were important predisposing factors. PMID- 7781535 TI - [Causes of pre- and perinatal piglet loss]. AB - The main part of the extensive embryonic losses in swine is usually attributed to endogenous regulatory processes. Beyond that a lot of endogenous and exogenous noxae can induce embryonic and fetal death. 60-80% of the preweaning mortality occur during the perinatal period, i.e. the time direct before farrowing until the third day of life. Aetiology, which generally is due to noninfectious causes, and clinical symptoms of perinatal mortality are described. PMID- 7781536 TI - [Effects of different anemia prevention forms on the blood parameters of the suckling piglet]. AB - The results of this trials confirmed the earlier experience that suckling piglets kept indoors, without iron supplementation, develop iron deficiency after 14 days postpartum. Piglets kept outdoors did not develop iron deficiency because of the daily iron supplementation from the ground. Principally, a single dose of iron either parenteral (injection) or oral (iron paste) would supply the iron requirements of the suckling piglets. However, iron injection provided even results than that of the oral supply where some piglets treated orally, developed anemia because oral treatment runs a greater risk of misapplication. Best results were obtained by use of an iron form which can be scattered on the ground during the whole period of suckling. The piglets would receive their iron requirement freely during this period. Another form of iron-electrolyte solution can be supplied through the drinking automate. However, the results were unfavorable and the piglets developed symptoms of anemia. This could be attributed to the fact that the piglets do not require extra fluids during the suckling period, when they receive enough dam milk. PMID- 7781537 TI - [The application of sonography for swine]. AB - The application of sonography at pigs has hitherto been confined to gynecological questions. In this examination applicabilities of the ultrasonic method are examined from the internal point of view. The sonographical normal picture of organ structures and the value of this method as aid for diagnosis of clinically manifest changes are shown. A 5MHz linear-scanner and a 3.5 MHz convex-scanner (76 degrees) turned out to be suitable. 112 patients of the Clinic of Internal Medicine II and additional 35 healthy pigs were examined. Preliminary examinations were made with isolated organs, which were scanned in a water bath. The sonographical findings of pathological changes could be secured by the postmortem findings. Within the scope of the main examinations, manners of representation and sonographical appearance of liver, gall-bladder, kidneys, urinary-bladder, stomach, lungs, muscular system, spine and transponder were elaborated. The standardized measuring of liver and kidney proved statistically secured dependencies among the measuring data and were significantly related with the body-weight. The ultrasonic guided puncture of gall-urinary bladder and of liquor cerebrospinalis could be carried out successfully. PMID- 7781538 TI - [The immune response in edema disease of weaned piglets measured with a recombinant B subunit of shiga-like toxin II]. AB - An outbreak of edema disease (ED) was monitored in 80 piglets after weaning over a period of 4 weeks. The shedding of Shiga-like toxin-IIe) producing Escherichia coli strains, the serum bactericidal activity (SBA) against SLTEC-IIe, and the antibody response against SLT-IIe were investigated. The antibody response was monitored by utilizing a glutathione-S-transferase (GST) + SLT-IIe B/SUB fusion protein (FRANKE et al., in press) for immunoblot assays. E. coli-strain GO15III (0141:K85ac) was diagnosed as SLT-IIe-producing E. coli by polymerase chain reaction, DNA hybridization and cytotoxicity assays. Maximum excretion of GO15III appeared between days 8 and 15 after weaning. On day 1 after weaning no piglet shed GO15III, while the number increased on day 8 to 53 (66.2%) and on day 15 to 59 (73.8%) of the piglets. 4 week after weaning, GO15III was only isolated from 23 (28.8%) of the piglets. In parallel, serum bactericidal activity against GO15III increased significantly in the sera of 73 (91.2%) piglets, reaching a stable maximum from day 15 on. During the first two weeks after weaning, no piglet yielded detectable SLT-IIe-IgG. However, the number of SLT-IIe-IgG positive piglets increased steadily from day 15. On day 15, 5 (6.2%) piglets were positive in SLT-IIe immunoblot analysis and 29 days after weaning the number increased to 31 (38.8%). These data represent the first serological monitoring of a natural outbreak of edema disease in piglets after weaning by using a recombinant fusion protein (GST+SLT-IIe B/SUB). The recombinant protein proved to be a useful diagnostical tool for monitoring the specific antibody status of piglets. PMID- 7781539 TI - [Treatment of swine with chronic pneumonia with chlortetracycline-medicated feed]. AB - 26 fattening pigs with spontaneous severe chronic bronchopneumonitis were orally treated with feed containing 800 ppm chlortetracycline (CTC) over 3 weeks. With the help of clinical investigation, transcutaneous measurement of the oxygen saturation of the blood, X-ray of the thorax and bronchoalveolar lavage significant effects could be measured during and after finishing the treatment. In 19 spontaneous fallen ill untreated control animals recovery could not be detected by the used methods. After the end of the 3 weeks interval there were significant differences between treated and untreated animals detectable. By this investigations practical observations that oral treatment with 800 ppm in fattening pigs is effective was verified. But because of pharmacokinetic data higher concentrations would be recommendable. In the treated pigs a significant increase of the oxygen saturation of the blood occurred not before the 8th day of treatment. This underlines the importance of sufficient length of the treatment interval. PMID- 7781540 TI - [The metabolism of trichothecenes in swine]. AB - Trichothecenes like T-2 toxin, diacetoxyscirpenol, and deoxynivalenol, which occur in feed, are metabolized preponderant in a biphasic way. Oxidation and hydrolysis are carried out in phase 1, while the transformation products are conjugated with glucuronic acid in phase 2; in addition, the epoxide ring is cleaved by the gut microflora. Metabolites of T-2 toxin are HT-2 toxin, 3' hydroxy-T-2 toxin, 3'-hydroxy-HT-2 toxin, neosolaniol, 4-deacetylneosolaniol, T-2 triol, T-2 tetraol, and de-epoxide T-2 tetraol. Diacetoxyscirpenol is transformed to 15-monoacetoxyscirpenol, scirpenetriol, de-epoxide 15-moneacetoxyscirpenol, and de-epoxide scirpenetriol. Deoxynivalenol undergoes no extensive metabolism; only the production of deoxynivalenol glucuronide and de-epoxide deoxynivalenol is assumed. As trichothecenes are rapid metabolized, the diagnosis of an intoxication by the analysis of samples of pig origin should be hardly possible; for the same reason, the possibility of an enrichment of trichothecene metabolites in edible tissues is graded as low. PMID- 7781541 TI - [The mineral content of calcium, phosphorus and magnesium in the serum and bones and the serum activity of alkaline phosphatase in slaughtered fattening pigs]. AB - The mineral content of serum and bones in 311 fattening pigs kept in a large scale farming operation was analyzed. Serum and metacarpal (III and IV) bone samples were obtained during slaughtering. The mean values of serum parameters as determined by automated dry-chemistry (Kodak Ektachem) were: Ca 2.80 +/- 0.20 mmol/l, P 3.08 +/- 0.67 mmol/l, Mg 1.21 +/- 0.24 mmol/l and Alkaline Phosphatase 211.25 +/- 56.91 U/l. Ash in bones was on average 62.85 +/- 2.07%. Ca- und Mg contents of bones were analyzed by atomic absorption spectrophotometry, the percentage found for Ca was 31.87 +/- 2.68%, and for Mg 0.64 +/- 0.05%. P in bones was determined spectrophotometrically by the vanadate-molybdate method and was 17.48 +/- 0.97%. The Ca/P-ratio in serum was 0.94 +/- 0.16, in bones 1.83 +/- 0.19, Ca/Mg in serum 2.37 +/- 0.31 and in bones 50.05 +/- 5.00. The parameters tested (Ca, P, Mg, AP) and the Ca/P- and Ca/Mg-ratios of minerals in serum and bones did not differ between sexes. Between all serum parameters positive correlations were found as well as between Ca and Mg in bones. Ca, P and Mg in bones were negatively correlated to Ca, P and Mg in serum, respectively. All results of the parameters examined were within the normal range for healthy fattening pigs, with the only exception that Ca-values in bones were lower than normal. A new method for preparing the bone samples for the analyses of minerals was established and can be recommended for further investigations. PMID- 7781542 TI - [Isolation of the agent of European swine plague from imported frozen wild boar meat]. AB - Since July 1993 imported frozen meat of wild boars has to be screened for the presence of HCV. The number of taken samples is given by the Ministry of health, sport and consumer protection. Until August 1994 the total number of 688 samples from different countries, have been examined. Three of them were found positive for HCV. The first one (November 1993) was from China, the other two positive samples were sent in one delivery from Romania in May 1994. PMID- 7781543 TI - [Fulminating malignant hyperthermia in swine--an alternative therapy concept]. AB - An inexpensive therapeutic concept compared to the dantrolene-therapy to counter the malignant hyperthermia (MH) is to be discussed, using a case-study from swine anaesthesia. Hyperventilating the animals (with O2), administering metamizol, beta-blocker, bicarbonate and sufficiently cooling the patient can, if the symptoms are recognized early enough, arrest the hypermetabolic cascade in its track. All the animals that were treated according to this scheme survived the (MH) crisis without any lasting post operative damage. PMID- 7781544 TI - [Clinical kidney function studies in sheep. III. Pathologic function changes in nephropathies of sheep and in urolithiasis of rams and billy goats]. AB - Examination of renal function have been carried out in sheep with acute prerenal (n = 6), renal (n = 15) or postrenal failure (n = 3), pyelocystitis (n = 4), and in cases of urolithiasis in rams (n = 16) and billy goats (n = 11) respectively. The calculation of parameters was done on the basis of the estimated weight dependent endogenous creatinine excretion. A control group of 56 healthy non pregnant or early pregnant (< 120th day of pregnancy) ewes have been used. The renal creatinine clearance was reduced and the absolute as well as the fractional renal water excretion was enhanced in all groups of sick animals. An elevated fractional excretion of sodium and phosphate could be seen as well. Functional disturbances could be observed in urolithiasis in like manner as in acute renal failure. There was proteinuria, glucosuria, excessive potassium excretion and often decreased plasma concentration of potassium in both syndromes. A hyperkalemia occurred only in the final state of urolithiasis. No clinical outcome of chronic nephropathies could be seen. Mortality of the described acute nephropathies was about 76%. The results of examination were suitable to control the course and restitution of renal function. They were not helpful for differential diagnosis and prognosis of acute renal failure. PMID- 7781545 TI - [Clinical findings in a lamb with congenital multiple abnormalities]. AB - A case of multiple, congenital malformations, with special emphasis on cardiac malformations (atrial- and ventricle septum defect, Ductus Botalli persistens, bilateral ventricle and atrial dilatation) in a lamb are described. Clinical findings, X-ray, ultrasound examination, electrocardio- and phonocardiogram, as well as pathology are discussed. PMID- 7781546 TI - Genital prolapse as a problem in rural community. PMID- 7781547 TI - Some haematological parameters in Malawian neonates. AB - Studies of haematological parameters were performed on 366 (177 male and 189 female) normal Malawian neonates with mean +/- s.d. birthweight of 2.99 +/- 0.37 (range 2.1-4.0) kg using a Nova Cell Track, Model Nova CT11. Cord anaemia (Cord Hb < 13.5g dl-1) was detected in 100 (27.3%) of the neonates. It was also shown that although the male babies had a significantly higher erythrocyte protoporphyrin level (p < 0.001) than the females, there were no significant differences (p > 0.05) in the red cell, white cell and platelet indices between the two sexes. When the haematological parameters of the 266 (72.7%) non-anaemic (Cord Hb > 13.5g dl-1) neonates were analysed, the mean +/- s.d. values which may serve as local reference standards were: Hb 16.0 +/- 1.7 (range 13.5-21.3) g dl 1, Hct 47.0 +/- 6.0 (range 36.5-67.5) percent, MCV 112.6 +/- 8.9 (range 72.2 131.0) fl, MCH 31.9 +/- 5.5 (range 24.4-48.5) pg, MCHC 33.5 +/- 2.8 (range 29.1 48.9) g dl-1 reticulocyte count 6.9 +/- 3.6 (range 1.2-25.0) percent, free erythrocyte protoporphyrin 3.3 +/- 0.9 (range 1.9-7.7) mgs ZPP gm-1 Hb, platelet count 269.9 +/- 57.7 (range 134.0-454.0) x 10(9) l-1 and total leucocyte count 12.3 +/- 4.8 (range 5.5-35.3) x 10(9) l-1. Further analysis of the differential wbc count disclosed normal levels of eosinophils and neutrophils similar to those given in standard haematology textbooks for Caucasian neonates; thus strengthening the belief that eosinophilia and relative neutropenia previously reported in adult Africans is not of genetic origin, but rather an acquired phenomena. PMID- 7781548 TI - Rapid surveys in support of district health information systems: an experience from Uganda. AB - The role of rapid health assessment in generating data other than routine reporting for a multi-element primary health care information system is presented. Rapid surveys, based on the adaptation of the WHO/EPI cluster survey methodology, may generate reliable and valid results useful for the support of a managerial PHC information system. However, because of the limitations inherent to the method, so far, only few studies have investigated more than few PHC related issues. The experience of a household rapid survey conducted in Arua District, Uganda, using a modified EPI cluster survey methodology, is reported. Rapid appraisal methods were used to prioritize the information requirement and to identify the survey items. Fully supervised teams of primary school teachers were used as interviewers. Data processing, check and analysis were speeded up by a lap-top computer, in spite of problems of erratic power. Within a 10-day time span between the start of the survey and the publishing of results, data on health services' utilization, health seeking behaviour, coverage of PHC services, including immunization, and anthropometric data on the nutritional status of under-five children were obtained. Standard errors and 95% confidence intervals were calculated taking into account the variability of the parameters under investigation and true design effects were computed. The findings were utilized for the identification of health priorities and the monitoring of effectiveness of programmes, as well as to validate routine reporting. The methodological package was built up looking at the local context, so that it could become an operational tool for the district health management team. PMID- 7781549 TI - The haematological profile of urban black Africans aged 15-64 years in the Cape Peninsula. AB - A stratified probability sample (n = 986) with quotas was drawn from black residential areas in the Cape Peninsula, South Africa. Subjects (n = 819) aged 15 64 years, participated in a coronary heart disease (CHD) risk factor survey, the BRISK Study. Nutritional status and prevalence of CHD was determined in this population undergoing rapid urbanization. Full blood and differential white blood cell counts provided data to calculate population reference values based on the 95% reference limits of the haematological parameter. Mean haemoglobin concentrations (Hb) in men (14.0 g/dl) and women (12.4 g/dl) were +/- 1.5 g/dl lower than previous South African reports. Mean BRISK Hb values were very similar to the World Health Organization's Hb cutoff criteria (< 13 g/dl men; < 12 g/dl women), indicating a possible high prevalence of anaemia. Significantly higher (P < 0.05) mean values for red cell indices were confirmed in men, which also reflected equally higher red blood cell counts (RBC), haematocrit (HCT) and mean corpuscular haemoglobin (MCH) values. Mean Hb values were significantly lower in the younger (15-24 years) and older (55-64 years) men compared with 25-54 year olds (P < 0.05). Hypochromic microcytic anaemia was more prevalent in women, possibly due to iron deficiency (ID), while macrocytic anaemia was more prevalent in men. No significant differences were noted in mean total and differential white blood cell counts (WBC) between men and women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781551 TI - Spectrum of childhood cancers in Malawi 1985-1993. AB - An analysis of seven hundred and ninety one children aged 0.2 to 14 years with confirmed malignant disease recorded by the Malawi National Cancer Registry over a period of 9 years is presented. Childhood cancer constituted 6.9% of all malignancies recorded during the study period. The top ten neoplasms in descending order of frequency were: non-Hodgkin's lymphoma 434 (54.9%), retinoblastoma 89 (11.3%), nephroblastoma 50 (6.3%), epithelial carcinoma 45 (5.7%), Hodgkin's disease 38 (4.8%), soft tissue sarcoma (excluding Kaposi): 34(4.3%), Kaposi's sarcoma 32 (4.0%), malignant tumours (not specified): 20 (2.5%), acute leukaemias 18(2.3%) and osteogenic sarcoma 16 (2.0%). Some differences noted in the pattern of neoplasms in this study from those of developed and developing African countries are discussed. The findings highlight the most common childhood malignancies in Malawi where intense research should be directed so that meaningful and cost effective therapeutic intervention programmes can be planned and developed. PMID- 7781550 TI - Utero-vaginal prolapse: a rural disability of the young. AB - A study consisting of 156 and 195 patients admitted to Gondar College and Gandhi Memorial hospitals respectively, for surgical corrections of vaginouterine prolapses of second and third degrees was carried out from June 1989 to June 1993. At Gondar, uterovaginal prolapses accounted for 19.9% of all major gynaecological operations in comparison to 17.2% at Gandhi. The mean ages for Gondar and Gandhi subjects were 38.09 +/- 11.52 and 42.17 +/- 13.16 years, respectively. In both centres there is statistically significant (p < 0.05) sequestration of especially third degree prolapse with increase in age. Mean parity of 5.6 +/- 2.7 children and 5.4 +/- 2.6 children have been obtained for Gondar and Gandhi groups, respectively. There is statistically significant increase (p < 0.05) of the second and more so of the third degree genito- urinary prolapse with increase in parity. Of the 125 housewives from the Gondar group, 114 (92.2%) were from the rural areas. The results of Gandhi group revealed that 143 (90.5%) out of 158 subjects were rural housewives. There is significant association of prolapse and occupation particularly with the rural housewives of both centres. The symptoms and signs of both centres were variable and dependent on degrees of prolapse; and the mean durations were 2.8 years +/- 2.9 years for Gondar and 2.4 years +/- 2.4 years for Gandhi, respectively. As a vaginal problem, vaginal surgical approaches yielded better results despite shortcomings of short term follow up. This paper based on two hospital records with similar results illustrates that it is mainly a rural problem and relatively of a younger population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781553 TI - Antistreptolysin O and antideoxyribonuclease B titres in blood donors and in patients with features of nonsuppurative sequelae of group A streptococcus infection in Tanzania. AB - Antistreptolysin O (ASO) and antideoxyribonuclease B (ADN B) titres were determined on sera from blood donors in Dar es Salaam, Tanzania and from Bergen, Norway and were compared with titres in patients with features of postgroup A streptococcal diseases in Dar es Salaam. The upper limit of normal ASO titres in Dar es Salaam was 200 mu/ml and for ADN B it was 300 u/ml while in Bergen the upper limit of normal ASO titre was 250 u/ml and that of ADN B was 100 u/ml. Titres of ASO in Dar es Salaam and Bergen were consistent with those from sub Saharan Africa and from other continents. Upper limit of normal ADN B titres in adults in Dar es Salaam were higher than those in Bergen probably due to higher frequencies of group A streptococcal skin infections in Dar es Salaam than in Bergen. Patients with features of postgroup A streptococcal diseases in Dar es Salaam had antibody titres above the upper limits of normal in 32.8% of the patients for ASO and in 45.9% for ADN B. ASO and ADN B titres or ASO and any other reliable test for antibody to group A streptococcus should be utilised together in providing strong evidence of recent infection with the group A streptococcus or of postgroup A streptococcal disease. PMID- 7781552 TI - Serologic markers for hepatitis B virus and hepatitis A virus in Bushmen in West Caprivi, Namibia. AB - A community based sero-epidemiological study was undertaken to determine the age specific prevalence rates of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection in a band of Bushmen in the West Caprivi, Namibia. All children tested and all but two of the adults tested showed the presence of anti-HAV antibodies. Nineteen individuals (18%) were positive for HBsAg and 65 (61%) individuals had serologic evidence of past exposure to HBV infection. PMID- 7781554 TI - Coronary heart disease in black Africans: an overview. AB - Coronary heart disease is still rare representing only 6% of all cardiovascular diseases in black Africans despite its increased incidence in recent years. Myocardial infarction in black Africans shows similar characteristics as those seen in patients aged under 40 years in the west, particularly regarding the frequency of infarction as the first manifestation of the disease, low prevalence of coronary artery stenosis and relatively common finding of normal coronary arteriography. Risk factor profile is the same as in western countries, but the haemoglobin S or C trait could be a unique one. The long-term outcome of infarction is severe and influenced by myocardial sequelae of imprecise origin; delayed hospitalisation; absence of thrombolysis and angioplasty; and socio economic and literacy problems. PMID- 7781555 TI - Myelopathies in Ethiopia. AB - From December 1990 to December 1993, 130 patients who had a lesion localized to the spinal cord were admitted to the Tikur Anbessa Hospital, Department of Internal Medicine, Addis Ababa. These patients accounted for 18.0% of all neurological admission to this department. The male/male female ratio was 1:8:1; the mean age was 40 years for these patients; 52% were from Addis Ababa City and 48% of them were coming from the rest of the country. Paraparesis or paraplegia (77%) and quadriparesis or quadriplegia (23%) were the commonest presenting complaints. Sensory level, sphincter dysfunction and bedsores were found in 70%, 54% and 14% of the cases respectively. Tuberculous spondylitis was found to be the leading cause accounting for 35 (26.9%), and HIV-1 myelopathies was the second common type accounting for 22 (16.9%) of spinal cord disease. Metastatic cord compression, tropical spastic paraparesis, (progressive non compressive myelopathy), cervical spondylosis, primary cord tumours and transverse myelitis were also not uncommon. Death related to sepsis or other causes were documented in 14 (10.8%). Follow-up was arranged on discharge, and only 45 (38.8%) patients were able to attend at least once the neurology referral clinic. Myelopathy is an important neurological disease and currently HIV-1 associated myelopathy has become the second important presumed cause. PMID- 7781556 TI - Tuberculosis of the spine in children at Muhimbili Medical Centre, Dar es Salaam. AB - A retrospective study of 22 children with tuberculosis of the spine who were managed at Paediatric Surgical Unit (PSU) of Muhimbili Medical Centre (MMC), Dar es Salaam between 1988 and 1993 was done. There were 12 boys and 10 girls of ages ranging from 3-13 years. Majority of the patients presented with back pain and/or deformity and weakness in the legs associated with difficulty in walking. The diagnosis was based on radiological as well as haematological findings. Two patients had associated lung lesions and these gave AFB positive sputum. Majority (63.5%) were thoracolumbar T11-L2. All patients received chemotherapy and in addition two had simple drainage of paravertebral abscesses and two debridement and bone grafting. There was no formal immobilization except that they had to sleep on hard beds. All gave a history of BCG vaccination scars. Mantoux or Heaf test was done on 16/22, patients of whom 11/16 (68.8%) were positive. One patient ended up with paraplegia, one with marked paraparesis and in 17/22 the kyphosis/gibbus increased. Laxity in the tuberculosis control programmes and the widespread of HIV could play part in what seems to be a flare up of tuberculosis infection in the recent past. PMID- 7781557 TI - Bladder carcinoma in Ibadan Nigeria: a changing trend? AB - A review of cases of bladder carcinoma in Ibadan, Nigeria between 1979-1989 suggest a changing trend with a rise in the frequency of transitional cell carcinoma (49.9%) relative to squamous cell carcinoma (SCC). Earlier reports from Ibadan indicated a preponderance of SCC. However, similar to other reports, SCC is more frequent amongst those aged 50 years and below (45.5%) compared to TCC (18%). This frequency has often been related to schistosomal infestation. Though the possibility of age-related factors are considered, the significance of changing environmental and socio-economic factors are highlighted. Whilst better public enlightenment and health education, may help in lowering the intensity of schistosomal infestation, increasing urbanization and industrialization may be increasing environmental factors that predispose to transitional (urothelial) cell carcinoma of the bladder. PMID- 7781558 TI - The effect on fibrinolytic system of blood plasma of Wister rats after feeding them with Coix mixed diet. AB - Experimental wister rats were fed on coix-mixed diet for 30 days in a view to study the effect of Coix feeding on the state of haemostatic mechanisms. Blood plasma which was obtained after cardiac puncture was analyzed for fibrinogen levels, euglobulin lysis time, fibrinolytic activity by protamin sulfate degradation and inhibitors of plasmin. These experimental models were set with a view to analyze situations mimicking processes associated with haemostasis and interpolate such situations in changes associated with the development of atherosclerosis. To study the plasma fibrinogen levels in experimental and control animals, spectrophotometric method was applied. Feeding the animals with coix-pellets mixed diet caused a decrease in fibrinogen levels as compared with controls. An overall decrease of this plasma protein was observed in both sexes. It was shown that euglobulin lysis time (ELT) was insignificantly changed in the experimental animals. However, fibrinolytic activity by degradation of protamin sulfate showed an increased fibrinolytic potential in experimental animals. In the same experimental models the analysis for the activity of inhibitors of plasmin showed no significant differences in mean values. It was found that coix has got vital nutritional value in lowering fibrinogen levels while at the same time creating a tendency of reducing fibrinolytic activity. More experiments should be conducted to show the possible mechanisms by which the observations can affect the development of atherosclerosis in man. PMID- 7781559 TI - Prescribing pattern of antibacterial drugs in a teaching hospital in Gondar, Ethiopia. AB - The prescribing pattern of antibacterial agents was analyzed by reviewing case notes of 407 patients discharged between October and November 1992 from a teaching hospital in Gondar, North-West Ethiopia. Seventy percent had received one or more antibacterials. Most exposure was in surgical ward (84%) followed by paediatric (82%), orthopaedic (78%), medical (72%), gynaecologic (58%) and obstetric (20%) wards. The antibacterials most frequently prescribed were penicillin G (25%), chloramphenical (24%), and ampicillin (20%). The total list numbered 13 and included no cephalosporines or quinoline derivatives. The preliminary survey indicated an inappropriate use of antibacterials and suggested the need to develop a policy on hospital antibacterial use. PMID- 7781560 TI - Analysis of caesarean delivery in Jimma Hospital, south-western Ethiopia. AB - In this prospective study, 100 mothers who have undergone caesarean section in Jimma Hospital from 23rd June 1992 to 24th September 1993 were analysed to determine the incidence, indications and post operative complications of caesarean delivery. During the study period, there were 1236 deliveries, of whom 100 mothers were delivered by caesarean section; giving a caesarean birth rate of 8%. The leading indications for caesarean section were cephalopelvic disproportion (44%), malpresentations and malpositions (21%), repeat caesarean section (16%), antepartum haemorrhage (8%) and foetal distress (6%), accounting for 95% of the indications for caesarean section. There was no maternal death, but the overall morbidity rate was 20%. The causes of morbidity were wound infection (27.1%), sepsis (21.4%), endometritis (33.3%), haemorrhage (8%) and wound dehiscence (10%). The gross perinatal mortality rate of 120 per 1000 live births was not significantly higher than the rate for all deliveries, which was 92.5% per 1000 live births (P < 0.5). The single most important cause of perinatal death was prolonged and obstructed labour. In order to reduce the high perinatal mortality and maternal morbidity, there is a strong and urgent need to prevent prolonged and obstructed labour through effective antenatal care and referral system. PMID- 7781561 TI - Pneumocystis carinii: a review. AB - Pneumocystis carinii has been increasingly recognized as an important cause of opportunistic infection in immune-deficient hosts. The prevalence of pneumocystis pneumonia (PCP) in Africa used to be neglected and underestimated due to difficult methods of isolating the infection. In this review, the authors discuss the nature of the parasite, and methods of diagnosis. PMID- 7781562 TI - Cost consideration in renal replacement therapy in Kenya. AB - End stage renal disease requiring renal replacement therapy is a common complication of several renal diseases that are seen in the tropics. World over, the costs of the various modalities of therapy that constitute renal replacement therapy, including hemodialysis, continuous ambulatory peritoneal dialysis and renal transplantation, is prohibitive. All the above modes of therapy are provided in Kenya, unlike most countries with similar level of socioeconomic development. This article analyses the factors behind the limited success that renal replacement therapy enjoys in Kenya, which is faced with more pressing basic problems of malnutrition and infection. PMID- 7781563 TI - Urinary tract infection with proteus species in a teaching hospital. AB - This study was undertaken to assess the prevalence of urinary tract infection due to proteus species, the predisposing factors, age and sex distribution, complications and the extent of drug resistance. A total of 580 patients were studied. Proteus species comprised 33 (9%) of the total number of bacterial isolates causing urinary tract infection during a one year study period between June 1991-May 1992. Proteus urinary tract infection was found to be the most common from the age of 55 years upwards in males, while in females, they were more evenly distributed. All the proteus isolates were completely resistant to ampicillin, tetracycline and cotrimoxazole. Ofloxacin was the most potent antibiotic (94.4%) sensitive, followed by gentamicin (83.3%) sensitive. Majority of the cases occurred in surgical department with more cases being nosocomially acquired than community. All male patients had at least one predisposing factor with catheterization being the commonest. To help reduce morbidity and mortality associated with urinary tract infection due to proteus species, strict aseptic catheter techniques and more efficient infection control measures must be reinforced. PMID- 7781564 TI - Interaction between nifedipine and digoxin in rats. AB - Possible nifedipine-digoxin interaction was investigated in rats by comparing lethal doses of intravenously infused digoxin in control and experimental rats. In the experimental rats, nifedipine was administered intraperitoneally, 30 minutes prior to infusing digoxin at a constant rate of 40mcg per minute. Results indicate that nifedipine administered within the dosage range 0.5-2.0mg per kg rat body weight, lowered the lethal dose of intravenously infused digoxin by 26 38% compared with control rats, thus indicating a synergistic effect between the two drugs. There was very little dose dependence of this effect. It is concluded that concomitant administration of nifedipine and digoxin in humans may lead to drug interactions. PMID- 7781565 TI - Growth deficient fetuses with absent or reversed umbilical artery end-diastolic flow are metabolically compromised. AB - Controversy continues regarding the clinical relevance of absent or reversed umbilical artery blood flow during diastole. The purpose of this study was to characterize the blood gas and lactate measurements of growth deficient fetuses with absent (ADF) or reversed (RDF) umbilical artery (UA) diastolic flow. In a descriptive study from February 1988 through October 1991, 42 consecutive structurally and karyotypically normal growth deficient fetuses identified to have either ADF or RDF diastolic flow in the UA were studied. Heparinized blood specimens were obtained from them and the pH, PCO2, PO2 and lactate measured. Fourteen of these specimens were obtained from the umbilical vein by cordocentesis and 28 at the caesarean delivery of non-labouring patients. Statistical analyses were performed using Fisher's exact test, Student t-test and linear correlation. All measured parameters in fetuses with ADF or RDF undergoing cordocentesis were significantly abnormal compared to gestational age corrected norms. Both the mean venous and arterial pH of fetuses with RDF were significantly lower than that of fetuses with ADF. With few exceptions, preoperative maternal oxygenation failed to correct the fetal hypoxaemia associated with either ADF or RDF. In the setting of severe fetal growth deficiency secondary to uteroplacental dysfunction, ADF and RDF are clinically reliable indicators of fetal compromise as determined by the umbilical blood gases. RDF is associated with a greater impairment of placental gas exchange than ADF. PMID- 7781566 TI - Vagal response to feeding tube insertion in preterm infants: has the key been found? AB - We prospectively studied the vagal response to feeding tube insertion in eight healthy preterm infants, on three occasions in each infant during the first three weeks of life. Heart rate, oxygen saturation, respiration and cerebral blood flow velocities were assessed before, during and immediately after insertion of an orogastric feeding tube. The whole procedure was recorded on video. The duration and quality of tube insertion and the behaviour of the infant were evaluated from the recordings. Twenty-one measurements in eight infants were evaluated. The heart-rate decrease observed immediately after tube insertion correlated significantly with the duration of tube insertion, the quicker the manipulation, the greater the heart-rate decrease (P = 0.000). The maximal decrease of oxygen saturation after tube insertion correlated with the degree of heart rate deceleration (P = 0.009). Significant alterations of the flow velocities were observed only when the heart rate fell below 80 beats/min. We speculate that such episodes of bradycardia can be avoided by carefully inserting the feeding tube over a period of at least 15 s. PMID- 7781567 TI - Pulmonary hypoplasia and fetal breathing in preterm premature rupture of membranes. AB - Forty-eight patients with premature rupture of membranes prior to 24 weeks gestation (PPROM) were studied to investigate whether there was any difference in fetal breathing movements in those fetuses that did or did not develop pulmonary hypoplasia. The diagnosis of pulmonary hypoplasia was made on the basis of ultrasound measurement of fetal lung length. A control group of fetuses with intact membranes and normal pregnancies at the same gestation was also studied. The group that developed pulmonary hypoplasia had significantly less breathing movements than those that did not develop pulmonary hypoplasia and controls. This reduction in breathing movements may contribute to the development of pulmonary hypoplasia. PMID- 7781568 TI - Three-dimensional ultrasound image of the fetal stomach: congenital duodenal obstruction in utero. AB - To quantitatively characterize the stereographic stomach configuration in utero, 11 fetuses (subject-group) with congenital duodenal obstruction, diagnosed antenatally, between 29 and 37 weeks' gestation were studied. Also included were 879 uncomplicated fetuses between 20 and 40 weeks' gestation as a control-group. Applying the algorithm which we devised: "Modeling a three-dimensional shape from a silhouette by detecting symmetry", we reconstructed the three-dimensional stomach configuration from a two-dimensional ultrasound image for each case. The statistical differences in two parameters, stomach volume and sphericity, between subject- and control-group fetuses, were analyzed using the Grubbs-Smirnoff's test at corresponding gestational ages. From 29 to 37 weeks' gestation, the stomach volume in the subject-group fetuses was found to increase greatly with advancing gestation, having significantly higher values than the control-group fetuses, whereas the stomach sphericity remained unchanged with no significant differences from the control-group fetuses. These findings indicate that the fetal stomach with duodenal obstruction maintains almost the same three dimensional portrayal in utero as that seen in uncomplicated fetuses, although the stomach becomes extremely enlarged. PMID- 7781569 TI - Volume delivery during positive pressure inflation--relationship to spontaneous tidal volume of neonates. AB - Volume delivery by positive pressure inflation was determined in 20 premature infants and 10 infants born at term on days 1 and 2. The spontaneous tidal volume, respiratory rate and inspiratory to expiratory (I:E) ratio were measured daily in the first week of life in an additional group of 20 infants born prematurely. Measurements were made using a pneumotachograph only when the infants were stable and had acceptable blood gases for at least 2 h. There was variability between individuals but the median delivered volume by positive pressure ventilation ranged between 4.9 and 6.1 ml/kg on days 1 and 2 and within the groups of different maturity. There was no significant difference in the results of infants born prematurely or at term or when studied on days 1 or 2. The median spontaneous tidal volume during the first week of life varied between 5.4 and 6.7 ml/kg; respiratory rate between 72 and 80 breaths/min and I:E ratio from 0.67 to 0.77. Postnatal age had no significant effect on the results. These results suggest volume delivery by positive pressure inflation during a stable period of ventilation is similar to the spontaneous tidal volume. PMID- 7781570 TI - Blood levels of vasoactive intestinal polypeptide in normal and growth retarded fetuses: relationship with acid-base and haemodynamic status. AB - The objectives of this study were (1) to detect vasoactive intestinal polypeptide in fetal blood obtained by cordocentesis (2) to examine possible changes in growth retarded fetuses and to establish relationships between its levels and fetal blood acid-base status as well as fetal haemodynamics as assessed by Doppler ultrasonography. Vasoactive intestinal polypeptide was measured in umbilical vein blood obtained at cordocentesis in 12 growth retarded fetuses and in 13 control fetuses. Umbilical vein pH and PO2 values were determined in all the cases. Before the procedure, Doppler indices were calculated from umbilical artery, middle cerebral artery, renal artery, cardiac outflow tracts and inferior vena cava. Simple and multiple stepwise regression analysis were performed to examine the relationships between Doppler indices, acid-base status and vasoactive intestinal polypeptide levels. In control fetuses, vasoactive intestinal polypeptide was always detectable in cord blood and its levels did not change with gestational age. In growth retarded fetuses, vasoactive intestinal polypeptide levels were higher and significantly related to umbilical vein PO2 levels, Pulsatility Index in umbilical artery, middle cerebral artery and renal artery, while no relationship was found with umbilical vein pH, cardiac and venous Doppler indices. Stepwise multiple regression demonstrated middle cerebral artery Pulsatility Index to be the best explanatory variable for vasoactive intestinal polypeptide levels. In conclusion, vasoactive intestinal polypeptide blood levels are increased in growth retarded fetuses and this increase is inversely related to the Doppler measured impedance to flow in middle cerebral artery. PMID- 7781571 TI - Median nerve conduction tests and Phalen's sign in carpal tunnel syndrome. AB - Carpal tunnel syndrome (CTS) is associated with sensory and/or motor dysfunction of the hand's fingers. The syndrome is caused by a continuous or intermittent pressure on the median nerve (NM) at the patient's wrist. 82 patients suffering from recent CTS symptoms, and 24 matched asymptomatic controls were tested. In the present study we examined five electrophysiological parameters and their correlations with a most commonly used clinical test--the Phalen test. The Phalen measure is the time from initial provocation until positive sign. The electrophysiological measurements are: NM Onset Sensory Velocity, NM Peak Sensory Velocity, NM Motor Nerve Velocity, NM Distal Motor Velocity, NM Residual Latency. Most of the symptomatic hands exhibited pathological values of their clinical or electrophysiological parameters. Phalen and Residual Latency were the most sensitive parameters. Phalen times were not significantly correlated with any of the five electrophysiological parameters, yet sensory velocity tended to decrease in patients with pathological Phalen values. PMID- 7781572 TI - Comparison between median and ulnar sensitive action potential (SAP) obtained with two different stimulation methods. AB - We studied the sensory action potentials (SAP) of median and ulnar nerves in four groups of 20-30, 30-40, 40-50 and 50-60 years old healthy subjects. In each group ten sensitive ulnar and median nerves were examined stimulating respectively V and III hand digital nerves, with two compared methods. In the former stimulus intensity was 20 mA, with a duration 0.1 msec, and SAP was recorded with averaging technique after 20 stimuli; in the latter the stimulus intensity was supra maximal (100 mA), with a duration 0.1 msec and a single SAP was recorded. The SAP's recording was performed by bipolar surface electrodes at the wrist, following conventional techniques. There was not statistically significant difference between SAP's latencies obtained with the two methods in each group, even if there was a decrease of the latency value obtained with supra maximal stimulus. Otherwise there was a statistically significant increase of SAP's amplitude obtained with supra maximal stimulus, above all in elderly people for median (p < 0.001) and ulnar (p < 0.0005) nerve. PMID- 7781573 TI - H-reflexes in the upper extremity and the effects of voluntary contraction. AB - We report a simple technique for obtaining H-reflexes from the extensor carpi radialis (ECR) muscle. In 50 normal test subjects, above-elbow stimulation of the radial nerve evoked ECR H-reflexes, in all 100 arms with facilitation, and in only 8 without facilitation. H-waves were less common in extensor digitorum communis and rare in brachioradialis; these could have been volume-conducted ECR responses. Median-nerve stimulation at the elbow evoked H-reflexes in 92 of the 100 flexor carpi radialis (FCR) muscles; 44 of these required no facilitation. Background EMG (facilitation) activity or an overlapping M-wave often obscured the H-wave onset: among the onsets considered reliable in FCR (67/92) and ECR (84/100), mean latencies were 16.2 msec and 16.5 msec respectively, and correlated well with subject height and arm length. There was no significant difference in latency obtained with and without facilitation for the FCR H reflexes and between techniques for the ECR H-reflexes. Right-left differences in latency ranged from 0 to 0.9 msec for ECR and 0 to 0.6 msec for FCR H-reflexes. PMID- 7781575 TI - Crossed R1 response of the blink reflex in peripheral facial palsy. AB - A patient with regenerated Bell's palsy showed a crossed R1 component of the blink reflex recorded from the healthy side while stimulating the affected side. Our observation supports the hypothesis that a short-circuit trigemino-facial pathway crossing the midline exists in normal subjects which is not activated under normal conditions, but may be engaged following peripheral facial nerve disease. PMID- 7781574 TI - Frequency of ulnar-to-median nerve anastomosis revisited. PMID- 7781576 TI - Electrophysiological studies in children with paralytic poliomyelitis. AB - H-reflex latency (H-RL) and H/M ratio were measured in normal children and children with paralytic poliomyelitis of 1-3 years of age. The H-RL was considerably increased in both the involved and uninvolved limbs of the patients, whereas the H/M ratio did not differ. The Mmax value in the involved limb was very low, and therefore, a corrected H/M ratio was calculated for that side only. The corrected H/M ratio was significantly less than the H/M ratio observed in the uninvolved and control limbs. The distal motor latency was also increased in the involved side. PMID- 7781577 TI - An analysis of VEP components in optic neuritis. AB - Various VEP parameters were analysed in 126 patients with multiple sclerosis, isolated optic neuritis or isolated myelopathy. The single most common deviation in eyes with clinical evidence of optic neuritis was a prolongation of the latency to P100. After the findings concerning P100 and N70 were combined two patterns of abnormalities emerged: 1) delayed P100 and delayed N70, 2) delayed P100 and absence of N70. In a few cases only one of the potentials was affected. Also in eyes without clinical evidence of optic neuritis the same patterns occurred but discrepancies between N70 and P100 were more common, especially the combination of normal P100 and delayed or absent N70. In about half of these cases the latency to P100 was close to the upper normal limit. It is concluded that in such cases the additional findings of an absent or delayed N70 is strongly suggestive of visual system dysfunction and that the inclusion of N70 in the analysis of VEP may increase the diagnostic yield of the examination. PMID- 7781579 TI - Prolonged brainstem auditory evoked potential latencies in tropical pancreatic diabetics with normal hearing. AB - Twenty patients with Tropical Pancreatic Diabetes (TPD) were evaluated by Brainstem Auditory Evoked Potentials (BAEP) in order to detect any possible subclinical involvement of auditory pathways. The latencies of BAEP Wave III (p < 0.009) and V (p < 0.47) as well as the Interpeak Latencies I-III (p < 0.002), and I-V (p < 0.019) were significantly prolonged in patients with TPD when compared to age and sex matched healthy volunteers. There was correlation between the abnormalities of BAEP and duration of diabetes (p < 0.006), male sex of patients (p < 0.05), and the presence of retinopathy (p < 0.003) and nephropathy (p < 0.38). There was no significant correlation with the age of the patients, type of treatment, blood sugar levels and presence of peripheral neuropathy. These changes suggest a subclinical involvement of the auditory pathways in TDP patients. PMID- 7781578 TI - Sacroiliac joint manipulation decreases the H-reflex. AB - Joint manipulation is widely utilized clinically to decrease pain and increase the range of motion of joints displaying limited mobility. Evidence of efficacy is based on subjective reports of symptom improvement as well as on the results of clinical trials. Experiments were designed to determine whether or not sacroiliac joint manipulation affects the amplitude of the Hoffman (H) reflex. Surface EMG recordings of the reflex response to electrical stimulation of the tibial nerve in the popliteal fossa were made from the soleus muscle. The averaged amplitudes of H-reflexes were compared on both legs before and after either sacroiliac joint manipulation or a sham procedure. H-reflex amplitude was significantly decreased (12.9%) in the ipsilateral leg (p < 0.001) following a sacroiliac joint manipulation while there was no significant alteration following the sham intervention. There was no significant alteration in reflex excitability in the contralateral leg to the sacroiliac joint manipulation. To further investigate the mechanism of these reflex alterations, the local anaesthetic cream EMLA (Astra Pharmaceuticals) was applied to the skin overlying the sacroiliac joint and the experiments were repeated on a different group of subjects. This was intended to determine if excitation of cutaneous afferents was responsible for the reflex excitability changes. There was still a significant decrease in reflex excitability (10.6%) following sacroiliac joint manipulation (p < 0.001). These findings indicate that joint manipulation exerts physiological effects on the central nervous system, probably at the segmental level. The fact that the changes persisted in the presence of cutaneous anaesthesia suggests that the reflex changes are likely to be mediated by joint and/or muscle afferents. PMID- 7781580 TI - Median sensory nerve conduction block during wrist flexion in the carpal tunnel syndrome. AB - A new method for diagnosing the carpal tunnel syndrome (CTS) is introduced. We have determined the time (T50) necessary to reach a 50% reduction in the amplitude of the median antidromic sensory nerve action potential during wrist flexion. Ten patients with anamnestic and neurophysiological evidence of CTS (group CTS) and 20 patients with CTS suspected on clinical grounds (group CTS?) were compared with 10 normal subjects. During wrist flexion the sensory conduction in the median nerve became partially blocked in all patients, and also in 8 out of 10 controls. The T50 value in 8 out of 10 CTS patients and in 14 out of 20 CTS? patients was below the lowest recorded value in the control group. It was shown that ischemia caused the blocking of the median nerve. Determination of T50 of the median nerve SNAP during wrist flexion has the potential to add to the sensitivity and specificity of the electrophysiological diagnosis of CTS. PMID- 7781581 TI - [Social adjustment and depression: value of the SAS-SR (Social Adjustment Scale Self-Report)]. AB - The Social Adjustment Scale Self-Report (SAS-SR) is a simple and inexpensive method, which allows the routine assessment of the patient's social adjustment, especially in the case of depression. Compared with other scales based on an interview with the patient, the SAS-SR is more sensitive to change in the patient's clinical status. The SAS-SR is a useful method as part of the detection of even mild depressions, regular aftercare evaluation of out-patients or as an outcome measure in longitudinal studies. A French version of the SAS-SR is now available and is currently under evaluation in a large-scale randomized therapeutic trial. PMID- 7781582 TI - [Factorial structure and internal consistency of the French version of the twenty item Toronto Alexithymia Scale in a group of 183 healthy probands]. AB - The factorial structure of the French version of the twenty-item Toronto Alexithymia Scale (TAS-20) was studied in a group of 183 healthy subjects. The TAS-20 represents the latest revised version of the TAS. His psychometric characteristics are clearly superior than the others alexithymia scales. Our subjects filled out the TAS whose 14 items are common with the TAS-20. We conducted our statistical analyses on these 14 items. A principal components analysis was carried out and yielded a two-factor solution where the items rating the ability to describe feelings and the items rating the ability to identify feelings constitute one sole factor. The second factor corresponds to the externally oriented factor. The internal consistency of the scale was also measured by the Cronbach alpha coefficient and by the correlation between each item and the total score. The value of the Cronbach alpha was 0.79 and the correlation between each item and the total score ranges from 0.19 (p < 0.05) to 0.69 (p < 0.001) with a mean of 0.52. Our results confirm a previous work on a group of 263 normal students which showed a two-factor solution of the TAS-20. The French version of the TAS-20 seems to be reliable and constitutes a useful instrument to study alexithymia in psychopathology. PMID- 7781584 TI - [The benzodiazepine receptor: the enigma of the endogenous ligand]. AB - The structure of the benzodiazepine receptor is nowadays well established and its potentialisation of GABA neurotransmission is known as the main action mechanism of benzodiazepinic drugs. Three categories of ligands have been also identified with radically different effects: the agonists (like diazepam and other anxiolytics), the antagonists (like flumazenil) and the inverse agonists which are anxiogenic, pro-convulsant and alerting (like beta-carbolines). By analogy with opiates system, the existence of a possible endogenous ligand has been proposed, and if such a substance really exists, it could be an important biological support of anxiety regulation. Many compounds with benzodiazepine receptor affinity have been extracted from the brain, the cerebrospinal fluid and the urine of animals but also of humans. Among these, some are artefacts, like ethyl-beta-carbolin, or their affinity are to low to be physiologically relevant. N-desmethyl-diazepam has been purified from the brain of never treated humans, but probably comes from diet or gut bacteria. An important candidate is the DBI (Diazepam Binding Inhibitor), which displays inverse agonist activity and is present in human organism. Its role as a modulator of GABAergic transmission is questioned. Likewise, the intervention of endogenous agonist compounds is possible during acquisition tasks with stress or anxiety in animals. There are also reasonable arguments to involve an agonist (sedative) ligand in the pathogenesis of hepatic encephalopathy. On the other hand, inverse agonists are not implicated in benzodiazepine withdrawal and panic disorder mechanisms. Lastly, probably indirect interactions between benzodiazepine receptor and cholecystokinin system are important to be considered, with possible consequences on anxiety regulations. PMID- 7781583 TI - [Central serotonin receptors and chronic treatment with selective serotonin reuptake inhibitors in the rat: comparative effects of fluoxetine and paroxetine]. AB - The hypothesis that a dysfunction of serotonergic neurotransmission is implicated in depression is supported by the clinical efficiency of selective serotonin (5 hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) in the treatment of depressive disorders. These drugs, such as fluoxetine and paroxetine, exert their antidepressant activity by increasing 5-HT concentration in the synaptic cleft and thus enhancing serotonergic neurotransmission. However, two to three weeks of treatment are necessary to see the first signs of clinical efficiency. Several hypothetical mechanisms have been put forward to account for this delay, taking into account pharmacokinetic considerations, neurotransmitter metabolism, and/or adaptive regulation of pre and/or post-synaptic receptors. The aim of this study was to look for such adaptive changes in the course of a 3-week treatment with fluoxetine (5 mg/kg/day, i.p.) or paroxetine (5 mg/kg/day, i.p.) in adult rats. In vitro binding and quantitative autoradiographic studies showed that neither 5 HT1A, 5-HT1B, 5-HT2A, nor 5-HT3 receptor binding sites in various brain areas were affected by these treatments. Furthermore, comparison of the specific binding of [3H]8-OH-DPAT to 5-HT1A receptors functionally coupled to G proteins with that of [3H]WAY 100635 to all 5-HT1A receptor binding sites (i.e. coupled and uncoupled with regard to G proteins) revealed no significant change in rats treated with either SSRI. Accordingly, the proportion of functional 5-HT1A receptors (i.e. those physically coupled to G proteins) appeared to remain unaltered all along a 3-week treatment with either fluoxetine or paroxetine. Nevertheless, in vitro electrophysiological recordings of serotonergic neurons in the dorsal raphe nucleus allowed the demonstration of a clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus, the potency of the 5-HT1A autoreceptor agonist, 8-OH-DPAT, to depress the firing of serotonergic neurons in brain stem slices was significantly reduced as soon as after a 3-day treatment with either SSRI. The proportion of recorded neurons showing desensitization of somatodendritic 5-HT1A autoreceptors then increased along the treatment, and was generally larger with fluoxetine than with paroxetine. As 5 HT1A autoreceptor desensitization can contribute to facilitate serotoninergic neurotransmission, the remarkable efficiency of fluoxetine to trigger this adaptive regulatory mechanism might account, at least partly, for its potent antidepressant activity. PMID- 7781585 TI - [Carbamazepine-fluvoxamine interaction. Consequences for the carbamazepine plasma level]. AB - The current practices concerning psychotropic drugs use plasma levels for the therapeutic adaptation and for the prevention of overdose and side effects. We observed, among two patients treated with constant dosages of carbamazepine (CBZ), that the addition of fluvoxamine (FLV) has increased significantly plasma levels of CBZ. The first patient, suffering of an affective bipolar trouble (ICD 10), was hospitalized for major depression. His admission treatment was CBZ (800 mg/day) and cyamemazine (75 mg/day). The introduction of the FLV (200 mg/day) was justified by the symptomatology. Then, plasma levels of CBZ increased progressively. No clinic or biological side effect was observed. Rapidly, CBZ oral dosages were decreased, but the plasma levels of CBZ reached the therapeutic window only when the FLV prescription was definitively stopped. The other patient was hospitalized for an acute exacerbation of a paranoiac disorder. He was treated with haloperidol for this episode. For five years, he received CBZ for neuralgia of the Trigeminus. The emergence of a depressive disorder justified a FLV treatment. From the introduction of FLV, plasma levels of CBZ were significantly increased. The reduction, then the stop of the FLV treatment, has allowed the standardization of plasma concentrations of CBZ. Three similar studies were found in the literature. The danger of this interaction was notified in two studies (one case each). Furthermore, in the third study (three cases) was put forward the hypothesis of a new therapeutic pathway. this hypothesis was suggested by the fact that these two medications were proposed independently to treat impulsive behaviors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781587 TI - [Re-reading: Theodule Ribot's The Psychology of Sentiments]. PMID- 7781586 TI - [Modification of cognitive functions by 2 anxiolytic treatments in patients suffering from generalized anxiety]. AB - The aim of this randomized, double-blind, multicentric study was to assess and compare cognitive impairment in patients treated with either lorazepam or hydroxyzine, for generalized anxiety. Only non depressed patients were selected according to MADRS criteria. The cognitive assessment was performed with the BEC 96 rating scale, the intensity of anxiety symptoms was evaluated through the Hamilton-anxiety and Covi scales. The level of relation, mood and sedation was assessed for each item with a visual analog scale (VAS). The patient's and investigator's opinion on the global efficiency of the treatment were also evaluated on VAS. After an 8-day wash-out period under placebo, the treatment was given in a double-blind way for 28 days: either hydroxyzine 25 mg at a daily dosage of 100 mg t.i.d. (25 mg - 25 mg - 50 mg), or lorazepam 1 mg at a daily dosage of 4 mg t.i.d. (1 mg - 1 mg - 2 mg). The results were as follows: after the 28-day treatment period, patients showed at the BEC 96 a cognitive improvement in both groups, but the improvement in the hydroxyzine group was significantly higher. Furthermore, the improvement appeared more quickly in the hydroxyzine group. The Hamilton-anxiety and Covi scales showed an improvement in the anxiety level in both groups with no significant difference. The visual analog scales assessing relation, mood and sedation improved in both groups as well as the patient's and investigator's opinion. The five assessments all showed a significant by higher improvement in the hydroxyzine group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781588 TI - [Suicide attempts and panic disorder: a study of 62 hospitalized suicidal patients]. AB - Suicidal behaviours are multifactorial behaviours. While, historically, anxiety has not been regarded as an important risk factor in suicidal behaviours, recent epidemiological studies carried out on general population or panic patients have evidenced the possible links between suicidal behaviours and the occurrence of panic attacks. The aim of our study was to validate the hypothesis which stipulates that panic disorder may contribute to an actualization of suicidal behaviour in trying to establish the prevalence of panic disorder in a population of suicidal attempters. The diagnoses were reached after an interview using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version modified for the study of Anxiety disorders (SADS-LA). The medical seriousness of the suicide attempts was assessed with the Risk Rescue Rating Scale (RRRS) of Weissman and Worden and the suicidal intent with the Suicidal Intent Scale of Beck (SIS). In the 62 suicide attempters hospitalized after minor or slightly more serious suicide attempts, we found high current and life-time prevalence of panic disorder (17.7% and 22.6% respectively). Comorbidity with major depressive episodes and addictive behaviours in suicide attempters with panic disorder was high. Current comorbidity rates were 72.8% and 27.3% respectively; life-time comorbidity rates were 71.4% and 21.4%. Patients who suffered from major depressive disorder with related panic disorder were given to more impulsive suicide attempts, even if the difference with depressed patients without panic disorder was statistically insignificant. PMID- 7781589 TI - [Four year follow-up of social adjustment of a cohort of schizophrenic patients]. AB - Sixty-seven first episode schizophrenic patients (PSE-Catego criteria) have been included in this study in order to evaluate their prognosis and the factors predictive of their evolution. Potential predictive factors consisted of anamnestic and demographic data, scores on the Disability Assessment Schedule (DAS-WHO) and relatives' Expressed Emotion index (EE), measured by the Camberwell Family Interview (CFI). The outcome was assessed monthly by the Global Assessment Scale (GAS/DSM III-R). At four years, 39 patients (58%) were still being followed. 33% of the patients presented a good evolution (EGF > or = 51) and 67% of the patients a bad evolution (EGF < 51). Four factors predictive of the psychosocial adaptation were extracted using regression analysis: premorbid psychosocial evolution, EE, sex and psychiatric family history. These 4 factors predicted correctly 85% of cases. Moreover, the monthly follow-up of these patients pointed to three types of evolution: the patients presenting a good and stable evolution (22%), those presenting a bad and stable evolution (33%) and those presenting an oscillating evolution which fluctuated between good and bad periods (44%). However, no predictive factors of the psychosocial adaptation of these oscillating patients could be identified through the statistical analysis. These results take all their importance regarding the treatment of schizophrenic patients, for whom the therapeutic plans which have to be settled should take into account their prognosis in the most precise manner. Moreover, the predictive value of EE on psychosocial adaptation for a 4 years period is confirmed. PMID- 7781590 TI - [Clinical study of a population of patients hospitalized for eating disorders. Discussion of DSM III-R diagnostic criteria]. AB - Patients consecutively referred for a clinical diagnosis of eating disorders to the Unit for Addictive Disorders at the University Hospital of Nantes were included in the study. The sample contained 95 patients (94 females, 1 male; mean age +/- SD: 24.1 +/- 6.5). All the patients were evaluated with the Computerized Multiple Diagnostic Instrument for Eating Disorders, which assesses diagnostic criteria for eating disorders from different international diagnostic classifications. Seven (7%) patients fulfilled the DSM III-R criteria for anorexia nervosa (AN) and 42 (44%) the DSM III-R criteria for bulimia nervosa. Two subgroups of bulimic patients were distinguished according to Body Mass Index [anorexia-bulimia (AB) if BMI was < 18 (n = 11, 12%) and normal weight bulimia (NWB) if BMI was > 18 (n = 31, 33%)]. Most patients (n = 46, 48%) did not fulfill DSM III-R criteria for AN or bulimia, and were given the residual DSM III-R diagnosis of eating disorder not otherwise specified (EDNOS). A comparison was made of the frequencies of the different weight control strategies displayed by the patients of the 4 subgroups. Vigorous exercise was more frequently used by AN patients than by patients of the 3 other subgroups. Vomiting was more frequent in bulimic patients, although this symptom was displayed by 29% of the AN patients and 24% of the EDNOS. Abuse of laxatives or diuretics was similar in the four subgroups. Use of diuretics was infrequent in the total sample of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781592 TI - Cytokines as mediators of autoimmune diabetes and diabetic complications. AB - Over the last several years, there has been a considerable and rapid expansion in our understanding of the cytokines. Insights into cytokine functions gained from basic biological studies are currently being applied to the study of autoimmune diabetes. It has become clear that cytokines are critical regulating elements involved in the processes of initiating, promoting, and effecting beta-cell destruction. It is also evident that cytokine functions in IDDM are determined by timing of appearance and local synthesis, as well as the prevailing cytokine and cellular milieu. Elucidating individual cytokine responses in IDDM may offer new insights into mechanisms of disease pathogenesis and may lead to novel cytokine based therapies for the treatment of IDDM. It may also be possible that the intensity or character of a patient's cytokine response to islet injury or to the metabolic changes inherent to diabetes may influence the ultimate expression of IDDM or its complications. Clearly, this rapidly expanding field of study should have a major impact on our understanding of diabetogenesis, our ability to intervene in our understanding of diabetogenesis, our ability to intervene in the disease process itself, and ultimately our capacity to care for individuals with IDDM. PMID- 7781591 TI - Insulin action and the insulin signaling network. PMID- 7781593 TI - The role of corticotropin-releasing factor and interleukin-1 in the regulation of neurons controlling reproductive functions. PMID- 7781594 TI - Structure-function relationships in the vitamin D endocrine system. PMID- 7781595 TI - FXR1, an autosomal homolog of the fragile X mental retardation gene. AB - Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1. PMID- 7781596 TI - Cloning and electrophysiological analysis of KST1, an inward rectifying K+ channel expressed in potato guard cells. AB - Potassium uptake by guard cells represents part of the osmotic motor which drives stomatal opening. Patch-clamp measurements have identified inward rectifying K+ channels capable of mediating K+ uptake in guard cells and various other plant cell types. Here we report the molecular cloning and characterization of a voltage-dependent K+ channel (KST1) from potato (Solanum tuberosum L.) guard cells. In situ hybridization shows expression of kst1 in guard cells. Two electrode voltage-clamp and patch-clamp studies of the gene product after cRNA injection into Xenopus oocytes identified KST1 as a slowly activating, voltage dependent, inward rectifying K+ channel. The single channel current voltage curve was linear in the range -160 to +20 mV, with a deduced single channel conductance of 7 pS in symmetrical 100 mM K+. This channel type, modulated by pH changes within the physiological range, required ATP for activation. In line with the properties of a K(+)-selective channel, KST1 was permeable to K+, Rb+ and NH4+ and excluded Na+ and Li+. Cs+ at submillimolar concentrations blocked the channel in a voltage-dependent manner. Related studies on potato guard cell protoplasts confirmed the biophysical characteristics of the kst1 gene product (KST1) in the heterologous expression system. Therefore, KST1 represents a major K+ uptake channel in potato guard cells. PMID- 7781597 TI - Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin. AB - Furin, a subtilisin-like eukaryotic endoprotease, is responsible for proteolytic cleavage of cellular and viral proteins transported via the constitutive secretory pathway. Cleavage occurs at the C-terminus of basic amino acid sequences, such as R-X-K/R-R and R-X-X-R. Furin was found predominantly in the trans-Golgi network (TGN), but also in clathrin-coated vesicles dispatched from the TGN, on the plasma membrane as an integral membrane protein and in the medium as an anchorless enzyme. When furin was vectorially expressed in normal rat kidney (NRK) cells it accumulated in the TGN similarly to the endogenous glycoprotein TGN38, often used as a TGN marker protein. The signals determining TGN targeting of furin were investigated by mutational analysis of the cytoplasmic tail of furin and by using the hemagglutinin (HA) of fowl plague virus, a protein with cell surface destination, as a reporter molecule, in which membrane anchor and cytoplasmic tail were replaced by the respective domains of furin. The membrane-spanning domain of furin grafted to HA does not localize the chimeric molecule to the TGN, whereas the cytoplasmic domain does. Results obtained on furin mutants with substitutions and deletions of amino acids in the cytoplasmic tail indicate that wild-type furin is concentrated in the TGN by a mechanism involving two independent targeting signals, which consist of the acidic peptide CPSDSEEDEG783 and the tetrapeptide YKGL765. The acidic signal in the cytoplasmic domain of a HA-furin chimera is necessary and sufficient to localize the reporter molecule to the TGN, whereas YKGL is a determinant for targeting to the endosomes. The data support the concept that the acidic signal, which is the dominant one, retains furin in the TGN, whereas the YKGL motif acts as a retrieval signal for furin that has escaped to the cell surface. PMID- 7781598 TI - A component of the chloroplastic protein import apparatus is targeted to the outer envelope membrane via a novel pathway. AB - A chloroplastic outer envelope membrane protein of 75 kDa (OEP75) was identified previously as a component of the protein import machinery. Here we provide additional evidence that OEP75 is a component of protein import, present the isolation of a cDNA clone encoding this protein, briefly describe its developmental expression and tissue specificity, and characterize its insertion into the outer envelope membrane. OEP75 was synthesized as a higher molecular weight precursor (prOEP75) which bound to isolated chloroplasts in an in vitro import assay and subsequently was processed to the mature form (mOEP75). During this import assay, two proteins intermediate in size between prOEP75 and mOEP75 were detected. One of these intermediates was also detected in chloroplast envelopes isolated from young pea leaves. Binding and processing of prOEP75 required ATP and one or more surface-exposed proteinaceous components, and was competed by prSSU, a stromal-targeted protein. We propose that the N-terminus of the prOEP75 transit peptide acts as a stromal-targeting domain and a central, hydrophobic region of this transit peptide acts as a stop-transfer domain. A complex route of insertion and processing of prOEP75 may exist to ensure high fidelity targeting of this import component. PMID- 7781600 TI - Contact of Shigella with host cells triggers release of Ipa invasins and is an essential function of invasiveness. AB - The invasion of colonic epithelial cells by Shigella, an early essential step for causing bacillary dysentery, is mediated by the IpaB, IpaC and IpaD proteins. Secretion of the Ipa proteins from Shigella requires functions encoded by the mxi and spa loci. In this study, we show that contact between the bacteria and epithelial cell triggers release of the Ipa proteins into the external medium, which results in a rapid decrease in levels of Ipa proteins presented on the cell surface. When the bacteria were used to infect polarized Caco-2 cells, release of Ipa proteins occurred efficiently from bacteria interacting with the basolateral surface rather than with the apical surface. Moreover, the interaction of bacteria with components of the extracellular matrix, such as fibronectin, laminin or collagen type IV, also stimulates the release of Ipa proteins. The release of Ipa proteins from Shigella required the surface-located Spa32 protein encoded by one of the spa genes on the large plasmid. PMID- 7781599 TI - Epitope mapping and direct visualization of the parallel, in-register arrangement of the double-stranded coiled-coil in the NuMA protein. AB - NuMA, a 238 kDa protein present in the nucleus during interphase, translocates to the spindle poles in mitosis. NuMA plays an essential role in mitosis, since microinjection of the NuMA SPN-3 monoclonal antibody causes mitotic arrest and micronuclei formation. We have mapped the approximate position of the epitopes of six monoclonal NuMA antibodies using recombinant NuMA fragments. The SPN-3 epitope has been located to residues 255-267 at the C-terminus of the first helical subdomain of the central rod domain and several residues crucial for antibody binding have been identified. To gain insight into the ultrastructure of NuMA, several defined fragments, as well as the full-length recombinant protein, were expressed in Escherichia coli and purified to homogeneity. They were then characterized by chemical cross-linking, circular dichroism spectra and electron microscopy. The results directly reveal the tripartate structure of NuMA. A long central rod domain is flanked by globular end domains. The rod is 207 nm long and is at least 90% alpha-helical. It reflects a double-stranded coiled-coil with the alpha-helices arranged parallel and in register. The NuMA protein thus forms the longest coiled-coil currently known. Our analyses reveal no indication that recombinant NuMA assembles into filaments or other higher order structures. PMID- 7781602 TI - Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function. AB - ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes. PMID- 7781601 TI - Involvement of the MAP kinase cascade in Xenopus mesoderm induction. AB - Mitogen-activated protein kinase (MAPK) is activated by MAPK kinase (MAPKK) in a variety of signaling pathways. This kinase cascade has been shown to function in cell proliferation and differentiation, but its role in early vertebrate development remains to be investigated. During early vertebrate embryogenesis, the induction and patterning of mesoderm are thought to be determined by signals from intercellular factors such as members of the fibroblast growth factor (FGF) family and members of the transforming growth factor-beta family. Here we show that the microinjection of either mRNA encoding a constitutively active mutant of MAPKK or mRNA encoding a constitutively active form of STE11, a MAPKK kinase, leads to the induction of mesoderm in ectodermal explants from Xenopus embryos. Moreover, the expression of MAPK phosphatase-1 (MKP-1, also called CL100) blocks the growth factor-stimulated mesoderm induction. Furthermore, injection of CL100 mRNA into two-cell stage embryos causes severe defects in gastrulation and posterior development. The effects induced by CL100 can be rescued by co injection of wild-type MAPK mRNA. Thus, the MAPK cascade may play a crucial role in early vertebrate embryogenesis, especially during mesoderm induction. PMID- 7781603 TI - Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila. AB - The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is required for Drk binding, probably because it provides a recognition site for the Drk SH2 domain. Interestingly, a mutation at this site does not completely block Sev function in vivo. This may suggest that Sev can signal in a Drk-independent, parallel pathway or that Drk can also bind to an intermediate docking protein. Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo. PMID- 7781604 TI - Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein. AB - SH-PTP1 is a protein tyrosine phosphatase (PTP) predominantly expressed in haematopoietic cells and containing two src homology-2 (SH2) domains. Here we report that SH-PTP1 is phosphorylated on both serine and tyrosine residues in response to thrombin or phorbol myristate acetate (PMA), which increased by 60 and 40%, respectively, SH-PTP1 activity. Thrombin-induced phosphorylation of SH PTP1 is an early signalling event (maximal within 10 s) involving neither integrin signalling, nor calcium, nor release of ADP or thromboxane A2. Moreover, in contrast with PMA, the effect of thrombin on the tyrosine phosphorylation of SH-PTP1 was hardly affected by GF109203X, a specific protein kinase C (PKC) inhibitor. Finally, phosphorylation of SH-PTP1 could be provoked in permeabilized platelets by thrombin or GTP gamma S. This was abolished by pertussis toxin, the specificity of this effect being verified with the megakaryocytic cell line Dami cell. Our data thus identify SH-PTP1 as an in vivo substrate of a putative protein tyrosine kinase linked to the thrombin receptor by a Gi protein. This might offer some clue to unravel the mechanism of thrombin not only in platelets but also in nucleated cells, where its mitogenic effect is known to involve pertussis toxin-sensitive G-proteins, tyrosine phosphorylation and the ras pathway. PMID- 7781605 TI - Interleukin 2 and erythropoietin activate STAT5/MGF via distinct pathways. AB - Signal transducers and activators of transcription (STAT) proteins play an important role in cytokine signal transduction in conjunction with Janus kinases (JAKs). MGF/STAT5 is known as prolactin regulated STAT. Here we demonstrate that interleukin 2 (IL-2) as well as erythropoietin (EPO) stimulate STAT5 and induce tyrosine phosphorylation of STAT5. These IL-2- and EPO-induced STATs have an identical DNA binding specificity and immunoreactivity. We also show that IL-4 induces a DNA binding factor which possesses similar, but distinct, DNA binding specificity from that of STAT5 and is immunologically different from STAT5. Analysis of two EPO receptor (EPOR) transfected CTLL-2 cell lines discloses that IL-2 activates JAK1 and JAK3 as well as STAT5, while EPO stimulates STAT5 and JAK2 in EPO-responsive CTLL-2 cells (ERT/E2). On the contrary, EPO activates neither JAK2 nor STAT5 in other cell lines that failed to respond to EPO (ERT cells). EPOR and JAK2 associate with each other regardless of EPO presence in ERT/E2 cells, however, such an interaction is not present in ERT cells. Thus, EPOR and JAK2 association seems to be important for EPO responsiveness in CTLL-2 cells. PMID- 7781606 TI - Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2. AB - The Pim-1 proto-oncogene is one of the most potent collaborators of the myc proto oncogenes in inducing lymphomagenesis in mice. Contrary to the profound effects when overexpressed in vivo, Pim-1-deficient mice showed only subtle phenotypic alterations, which could indicate the presence of redundantly acting genes. In line with this, a PCR-based screen has led to the identification of a closely homologous gene, Pim-2. The X-linked Pim-2 gene is 53% identical to Pim-1 at the amino acid level and shares substrate preference and the usage of non-AUG initiation codons with Pim-1. We have used these data to test whether the strong synergistic interaction between Pim-1 and c-myc can be utilized to gain access to Pim-1 compensatory pathways. We reasoned that, upon proviral tagging in compound mutant mice (E mu-myc/Pim-1-/- mice), the selective advantage of cells carrying provirally activated genes, that act downstream from or parallel to Pim-1, would increase. We show here that this is the case. A dramatic increase (from 15 to 80%) was found in the frequency of proviral activation of the Pim-2 gene. These data show that the described strategy of 'complementation tagging' represents a powerful new tool to identify components of pathways involved in processes as complex as multistep tumorigenesis. PMID- 7781607 TI - Silencing of Escherichia coli bgl promoter by flanking sequence elements. AB - Silencing of a transcriptional unit by flanking sequence elements has so far only been described for eukaryotic systems. Here, a similar system is described in bacteria. The Escherichia coli bgl operon (beta-glucoside utilization) is normally cryptic due to very low promoter activity. However, low activity is not attributable to the quality of the promoter itself but is caused by its chromosomal context. The bgl promoter is perfectly active when tested outside of its normal context of a stretch of a few hundred base pairs. In addition, other promoters become inactivated when placed into the bgl region. Both the deletion of an upstream sequence element and the replacement of sequences located downstream result in promoter de-repression, demonstrating that silencing of promoters within this stretch of DNA in vivo is an active process brought about by the combined action of upstream and downstream chromosomal elements. PMID- 7781608 TI - Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32. AB - Escherichia coli FtsH is an essential integral membrane protein that has an AAA type ATPase domain at its C-terminal cytoplasmic part, which is homologous to at least three ATPase subunits of the eukaryotic 26S proteasome. We report here that FtsH is involved in degradation of the heat-shock transcription factor sigma 32, a key element in the regulation of the E. coli heat-shock response. In the temperature-sensitive ftsH1 mutant, the amount of sigma 32 at a non-permissive temperature was higher than in the wild-type under certain conditions due to a reduced rate of degradation. In an in vitro system with purified components, FtsH catalyzed ATP-dependent degradation of biologically active histidine-tagged sigma 32. FtsH has a zinc-binding motif similar to the active site of zinc metalloproteases. Protease activity of FtsH for histidine-tagged sigma 32 was stimulated by Zn2+ and strongly inhibited by the heavy metal chelating agent o phenanthroline. We conclude that FtsH is a novel membrane-bound, ATP-dependent metalloprotease with activity for sigma 32. These findings indicate a new mechanism of gene regulation in E. coli. PMID- 7781609 TI - Fate of linear and supercoiled multinucleosomic templates during transcription. AB - Electron microscopy was used to monitor the fate of reconstituted nucleosome cores during in vitro transcription of long linear and supercoiled multinucleosomic templates by the prokaryotic T7 RNA polymerase and the eukaryotic RNA polymerase II. Transcription by T7 RNA polymerase disrupted the nucleosomal configuration in the transcribed region, while nucleosomes were preserved upstream of the transcription initiation site and in front of the polymerase. Nucleosome disruption was independent of the topology of the template, linear or supercoiled, and of the presence or absence of nucleosome positioning sequences in the transcribed region. In contrast, the nucleosomal configuration was preserved during transcription from the vitellogenin B1 promoter with RNA polymerase II in a rat liver total nuclear extract. However, the persistence of nucleosomes on the template was not RNA polymerase II specific, but was dependent on another activity present in the nuclear extract. This was demonstrated by addition of the extract to the T7 RNA polymerase transcription reaction, which resulted in retention of the nucleosomal configuration. This nuclear activity, also found in HeLa cell nuclei, is heat sensitive and could not be substituted by nucleoplasmin, chromatin assembly factor (CAF-I) or a combination thereof. Altogether, these results identify a novel nuclear activity, called herein transcription-dependent chromatin stabilizing activity I or TCSA-I, which may be involved in a nucleosome transfer mechanism during transcription. PMID- 7781610 TI - Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. AB - Many yeast promoters contain homopolymeric dA:dT sequences that affect nucleosome formation in vitro and are required for wild-type levels of transcription in vivo. Here, we show that poly(dA:dT) is a novel promoter element whose function depends on its intrinsic structure, not its interaction with sequence-specific, DNA-binding proteins. First, poly(dA:dT) stimulates Gcn4-activated transcription in a manner that is length dependent and inversely related to intracellular Gcn4 levels. Second, Datin, the only known poly(dA:dT)-binding protein, behaves as a repressor through poly(dA:dT) sequences. Third, poly(dG:dC), a structurally dissimilar homopolymer that also affects nucleosomes, has transcriptional properties virtually identical to those of poly(dA:dT). Three probes of chromatin structure including HinfI endonuclease cleavage in vivo indicate that poly(dA:dT) increases accessibility of the Gcn4 binding site and adjacent sequences in physiological chromatin. These observations suggest that, by virtue of its intrinsic structure, poly(dA:dT) locally affects nucleosomes and increases the accessibility of transcription factors bound to nearby sequences. PMID- 7781611 TI - A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B. AB - The inducible, higher eukaryotic transcription factor NF-kappa B is activated by a variety of external stimuli including inflammatory cytokines, viral and bacterial infection and UV irradiation. Here we show that internal stress, caused by the accumulation of proteins in the endoplasmic reticulum (ER), also induces NF-kappa B DNA binding as well as kappa B-dependent gene expression. This was observed upon expression of immunoglobulin mu chains in the absence of light chains and by treatment of cells with several agents known to cause ER stress, such as tunicamycin, brefeldin A, 2-deoxyglucose and thapsigsargin. The transcription factor AP-1 was weakly induced under similar conditions. Overexpression of NF-kappa B subunits did not influence expression of the gene encoding grp78/BiP, a protein induced by various forms of ER stress. Likewise, the glucosidase inhibitor castanospermine, which induced grp78/BiP expression, failed to activate NF-kappa B, while the antioxidant dithiothreitol augmented grp78/BiP expression but prevented activation of NF-kappa B. Hence, NF-kappa B participates in a novel ER-nuclear signal transduction pathway distinct from the unfolded-protein-response described previously. We provide evidence that the ER can produce at least two distinct signals in response to a functional impairment. One is emitted by the presence of unfolded proteins, the other in response to overloading of the organelle, for example through the overexpression of secretory proteins. PMID- 7781613 TI - Codon-dependent conformational change of elongation factor Tu preceding GTP hydrolysis on the ribosome. AB - The mechanisms by which elongation factor Tu (EF-Tu) promotes the binding of aminoacyl-tRNA to the A site of the ribosome and, in particular, how GTP hydrolysis by EF-Tu is triggered on the ribosome, are not understood. We report steady-state and time-resolved fluorescence measurements, performed in the Escherichia coli system, in which the interaction of the complex EF-Tu.GTP.Phe tRNAPhe with the ribosomal A site is monitored by the fluorescence changes of either mant-dGTP [3'-O-(N-methylanthraniloyl)-2-deoxyguanosine triphosphate], replacing GTP in the complex, or of wybutine in the anticodon loop of the tRNA. Additionally, GTP hydrolysis is measured by the quench-flow technique. We find that codon-anticodon interaction induces a rapid rearrangement within the G domain of EF-Tu around the bound nucleotide, which is followed by GTP hydrolysis at an approximately 1.5-fold lower rate. In the presence of kirromycin, the activated conformation of EF-Tu appears to be frozen. The steps following GTP hydrolysis--the switch of EF-Tu to the GDP-bound conformation, the release of aminoacyl-tRNA from EF-Tu to the A site, and the dissociation of EF-Tu-GDP from the ribosome--which are altogether suppressed by kirromycin, are not distinguished kinetically. The results suggest that codon recognition by the ternary complex on the ribosome initiates a series of structural rearrangements resulting in a conformational change of EF-Tu, possibly involving the effector region, which, in turn, triggers GTP hydrolysis. PMID- 7781612 TI - Extensive interactions of PRP8 protein with the 5' and 3' splice sites during splicing suggest a role in stabilization of exon alignment by U5 snRNA. AB - Precursor RNAs containing 4-thiouridine at specific sites were used with UV crosslinking to map the binding sites of the yeast protein splicing factor PRP8. PRP8 protein interacts with a region of at least eight exon nucleotides at the 5' splice site and a minimum of 13 exon nucleotides and part of the polypyrimidine tract in the 3' splice site region. Crosslinking of PRP8 to mutant and duplicated 3' splice sites indicated that the interaction is not sequence specific, nor does it depend on the splice site being functional. Binding of PRP8 to the 5' exon was established before step 1 and to the 3' splice site region after step 1 of splicing. These interactions place PRP8 close to the proposed catalytic core of the spliceosome during both transesterification reactions. To date, this represents the most extensive mapping of the binding site(s) of a splicing factor on the substrate RNA. We propose that the large binding sites of PRP8 stabilize the intrinsically weaker interactions of U5 snRNA with both exons at the splice sites for exon alignment by the U5 snRNP. PMID- 7781614 TI - Biogenesis, structure and function of the yeast 20S proteasome. AB - Intracellular degradation of many eukaryotic proteins requires their covalent ligation to ubiquitin. We previously identified a ubiquitin-dependent degradation pathway in the yeast Saccharomyces cerevisiae, the DOA pathway. Independent work has suggested that a major mechanism of cellular proteolysis involves a large multisubunit protease(s) called the 20S proteasome. We demonstrate here that Doa3 and Doa5, two essential components of the DOA pathway, are subunits of the proteasome. Biochemical analyses of purified mutant proteasomes suggest functions for several conserved proteasome subunit residues. All detectable proteasome particles purified from doa3 or doa5 cells have altered physical properties; however, the mutant particles contain the same 14 different subunits as the wild type enzyme, indicating that most or all yeast 20S proteasomes comprise a uniform population of hetero-oligomeric complexes rather than a mixture of particles of variable subunit composition. Unexpectedly, we found that the yeast Doa3 and Pre3 subunits are synthesized as precursors which are processed in a manner apparently identical to that of related mammalian proteasome subunits implicated in antigen presentation, suggesting that biogenesis of the proteasome particle is highly conserved between yeast and mammals. PMID- 7781615 TI - Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. AB - Characterization of the proteins that interact with replication origins, as well as characterization of the mechanisms by which the levels and activities of these proteins are regulated during the cell cycle, is required to understand the initiation of chromosomal DNA replication in eukaryotic cells. We have previously shown that the first detectable step in the assembly of initiation complexes in vivo involves the binding of the multisubunit origin recognition complex (ORC) and the general transcription/replication factor ABF1 protein to origins. In this paper we show that ORC is present in cells at low levels, corresponding to little more than one complete complex per replication origin, indicating that in vivo origin recognition by ORC is extremely efficient. We show that this efficient recognition requires two sequence elements, the essential A element containing the ARS consensus sequence and the functionally important B1 element, both in vitro and in vivo. Moreover, we show that origin binding by ORC in vivo does not require any other functional sequence element, indicating that it occurs independently of the binding of other factors, such as ABF1. Our results suggest a model for the roles of the individual elements of yeast replication origins. PMID- 7781617 TI - Effects of Holliday junction position on Xer-mediated recombination in vitro. AB - Site-specific recombination mediated by XerC and XerD functions in the segregation of circular replicons in Escherichia coli. A key feature of most models of recombination for the family of recombinases to which XerC and XerD belong is that a Holliday junction forms at the position of the first pair of recombinase-mediated strand exchanges and then branch migrates 6-8 bp to the position of the second pair of strand exchanges. We have tested this hypothesis for Xer recombination by studying the effects of junction position on XerC mediated strand exchange in vitro. Recombination of synthetic Holliday junction substrates in which junction mobility was constrained to a region extending over or removed away from the normal cleavage and exchange point was analysed. All substrates undergo strand cleavage at the normal position. We infer that the Holliday junction need not be at this position during strand cleavage and exchange. With substrates in which the Holliday junction is constrained to a region away from the XerC-mediated cleavage point, strand exchange generates products with the predicted mispaired bases. PMID- 7781618 TI - McrB: a prokaryotic protein specifically recognizing DNA containing modified cytosine residues. AB - Restriction of DNA by the Escherichia coli K-12 McrBC restriction endonuclease, which consists of the two subunits McrB and McrC, depends on the presence of modified cytosine residues in a special constellation. From previous work by others it was known that restriction of 5-methylcytosine-containing DNA requires two methylated 5'-PuC sites separated by approximately 40-80 non-defined base pairs. Here we show that binding of the McrBC nuclease is mediated exclusively by the McrB subunit. McrB has a low affinity for non-methylated DNA, with which it forms low molecular weight complexes. The affinity for DNA is significantly increased, with variations depending on the sequence context, by hemi- or fully methylated 5'-PuC sites. Binding to such substrates yields high molecular weight complexes, presumably involving several McrB molecules. Methylation at unique 5' PuC sites can be sufficient to stimulate DNA binding by McrB. As such substrates are not cleaved by the nuclease, restriction apparently requires the coordinated interaction of molecules bound to neighbouring 5'-PumC sites. The binding properties of McrB exhibit some similarities to recently identified eukaryotic proteins interacting in a non-sequence-specific manner with DNA containing methylated 5'-CpG sequences and might point to a common molecular origin of these proteins. In addition to DNA, McrB also binds GTP, an essential cofactor in DNA restriction by McrBC. McrC neither binds to DNA nor modulates the DNA binding potential of McrB. As McrC is essential for restriction it appears to predominantly function in catalysis. PMID- 7781616 TI - Primosome assembly site in Bacillus subtilis. AB - A single-strand initiation site was detected on the Enterococcus faecalis plasmid pAM beta 1 by its ability to prevent accumulation of single stranded DNA of a rolling circle plasmid, both in Bacillus subtilis and Staphylococcus aureus. This site, designated ssiA, is located on the lagging strand template, approximately 150 bp downstream from the replication origin. ssiA priming activity requires the DnaE primase, the DnaC replication fork helicase, as well as the products of the dnaB, dnaD and dnaI genes of B.subtilis, but not the RNA polymerase. The primase and the replication fork helicase requirements indicate that ssiA is a primosome assembly site. Interestingly, the pAM beta 1 lagging strand synthesis is inefficient when any of the proteins involved in ssiA activity is mutated, but occurs efficiently in the absence of ssiA. This suggests that normal plasmid replication requires primosome assembly and that the primosome can assemble not only at ssiA but also elsewhere on the plasmid. This work for the first time describes a primosome in a Gram-positive bacterium. Involvement of the B.subtilis proteins DnaB, DnaD and DnaI, which do not have any known analogue in Escherichia coli, raises the possibility that primosome assembly and/or function in B.subtilis differs from that in E.coli. PMID- 7781620 TI - Pituitary disorders during pregnancy. AB - A number of morphologic and physiologic changes accompany pregnancy such as an increase in lactotrophs and prolactin production, and a decrease in gonadotropins and GH. The hormonal milieu can affect patients with prolactinomas, especially macroadenomas, to cause an increase in size in a minority of patients. Complications are treated with bromocryptine. Enlargement of GH-secreting tumors with acromegaly may respond to bromocryptine and possibly to octreotide. Pituitary tumors causing Cushing's syndrome may need removal if major complications develop. Hypopituitarism during pregnancy may be the result of lymphocytic hypophysitis or antepartum pituitary necrosis, and in the postpartum period may be because of postpartum hemorrhage and pituitary necrosis. These abnormalities need prompt recognition and hormonal replacement therapy with neurosurgical decompression to avoid serious morbidity and mortality. Posterior pituitary problems in pregnancy usually manifest by diabetes insipidus, with a pregnancy-specific variety resulting from excessive degradation of AVP by placental vasopressinase. The condition is treated with an analogue dDAVP, which is resistant to vasopressinase. PMID- 7781619 TI - Sequence variability within the tobacco retrotransposon Tnt1 population. AB - Retroviruses consist of populations of different but closely related genomes referred to as quasispecies. A high mutation rate coupled with extremely rapid replication cycles allows these sequences to be highly interconnected in a rapid equilibrium. It is not known if other retroelements can show a similar population structure. We show here that when the tobacco Tnt1 retrotransposon is expressed, its RNA is not a unique sequence but a population of different but closely related sequences. Nevertheless, this highly variable population is not in a rapid equilibrium and could not be considered as a quasispecies. We have thus named the structure presented by Tnt1 RNA quasispecies-like. We show that the expression of Tnt1 in different situations gives rise to different populations of Tnt1 RNA sequences, suggesting an adaptive capacity for this element. The analysis of the variability within the total genomic population of Tnt1 elements shows that mutations frequently occur in important regulatory elements and that defective elements are often produced. We discuss the implications that this population structure could have for Tnt1 regulation and evolution. PMID- 7781622 TI - Adrenal disorders of pregnancy. AB - In normal pregnancy, the maternal adrenal gland adapts to the physiologic changes necessary to sustain gestation. These changes protect the fetus and the mother, allowing for increased shunting of nutrients to the fetus and protection of immunologic rejection. The adrenal disorders pertinent to pregnancy include overactive and underactive secretion of adrenocortical hormones and tumors that secrete too much catecholamine. In addition, iatrogenic hypercortisolemia may be necessary to treat the mother for underlying diseases. The impact of iatrogenic hypercortisolemia on the fetus is addressed also. PMID- 7781621 TI - Pancreatic disorders of pregnancy. Diagnosis, management, and outcome of gestational diabetes. AB - Gestational diabetes is one of the more common medical problems of pregnancy. This article reviews the literature regarding the diagnosis and treatment and the controversy that surrounds gestational diabetes. The need for stricter guidelines for diagnosis and treatment and the evidence supporting this need are presented. Long-term follow-up evaluation for women with gestational diabetes and for their children is discussed. PMID- 7781623 TI - Calcium disorders of pregnancy. AB - This article begins with a discussion on changes in the maternal calcium parathyroid axis in response to pregnancy, followed by calcium disorders that can take place during pregnancy. Hypercalcemia and its subsequent disorders, including hyperparathyroidism, hypocalciuric hypercalcemia, and thyroid disease, are reviewed. Also, hypocalcemia and its subsequent disorders, including hypoparathyroidism, vitamin D deficiency, and hypomagnesemia, are addressed. Concluding the article are discussions on bone status and osteoporosis, calcium metabolism in pregnancy-induced hypertension and preeclampsia, and nephrolithiasis in pregnancy. PMID- 7781624 TI - Ovarian disorders of pregnancy. AB - Hormonal ovarian disorders are uncommon during pregnancy and present primarily as ovarian masses. The two most common conditions are luteomas and hyperreactio luteinalis. The most common clinical manifestation is maternal virilization, which occasionally affects the fetus also. Rarely, an acute abdomen can result from hemorrhage or torsion of the mass. Because most of the entities regress spontaneously following delivery, a conservative management approach that includes preserving the ovaries is warranted. PMID- 7781626 TI - Immunologic response in pregnancy. Its role in endocrine disorders of pregnancy and influence on the course of maternal autoimmune diseases. AB - During gestation, the immune system is challenged with establishing tolerance to the partial allograft represented by the paternal contribution to the fetal genome. That fact that cell-mediated immunity is decreased while T-cell-dependent immunoglobin production remains intact or is increased is generally accepted. This latter phenomenon can be placed in teleological perspective in terms of providing passive immunity to the fetus. T-cell lineages that diverge based on function and cytokine production have been identified. Pregnancy is associated with a relative increase in Th2-associated immunity, characterized by increased production of the cytokines IL-4 and IL-10. These changes occur concomitantly with increased immunoglobulin production and decreased Th1 immunity. IL-2 and interferon secretion characterize Th1 immunity, facilitating allograft rejection. These changes in Th1 and Th2 have implications for the clinical course of a several autoimmune diseases that may complicate pregnancy and the postpartum period. PMID- 7781625 TI - Relaxin and its role in pregnancy. AB - Relaxin is a 6000-d polypeptide, structurally related to insulin and the insulin like growth factors. Unlike insulin, the structure of which is remarkably well conserved among the vertebrates, relaxin sequences can vary by more than 50% between different species. Despite these large sequence variations, relaxins (with few exceptions) have very similar biologic activities in animal test systems. The reason for this has recently come to light: the receptor binding region of the B chain, in contrast to the rest of the molecule, is highly conserved between species. Relaxin is measured by bioassays employing interpubic ligament formation in mice and guinea pigs, and by inhibition of uterine motility. A more sensitive and efficient bioassay is urgently needed. In women, the target organs for relaxin are the uterine cervix, myometrium, endometrium, and decidua. Other presumptive but unproven targets are the pubic symphysis and sacroiliac joints, mammary glands, and pituitary gland. Circulating relaxin is secreted by the corpus luteum. The placenta, decidua, or both also produce relaxin, which does not enter the circulation but may act in an autocrine or paracrine fashion. hCG is a stimulus to luteal relaxin secretion. Other regulatory factors are poorly defined. Aluteal women are hyporelaxinemic, and yet are capable of normal vaginal delivery of their infants. Local effects of placental or decidual relaxin cannot be discounted in such subjects. Hyperrelaxinemia may occur in women with multiple gestations and ovarian stimulation, and may be associated with increased premature births. Serum relaxin also is elevated in pregnant diabetics, but its role in this condition has not been defined. Clearly, further investigations are needed to delineate the precise role of relaxin in human pregnancy. PMID- 7781628 TI - Pancreatic disorders of pregnancy. Pregestational diabetes. AB - The outcome of pregnancies complicated by pregestational diabetes, both insulin dependent and non-insulin-dependent, has changed dramatically since the discovery of insulin in the early 1920s. Now, patients with pregestational diabetes can safely undergo a pregnancy and be assured that the infant will be healthy. Unfortunately, a finite risk of problems still may occur, including congenital malformations, spontaneous abortions, and diabetic fetopathy classically manifest as a macrosomic infant. Treatment strategies, although tedious and sometimes onerous, do minimize these risks. PMID- 7781627 TI - Thyroid disorders of pregnancy. AB - Practical aspects in the management of thyroid diseases in pregnancy are reviewed. Information on the hypothalamic-pituitary thyroid axis function in pregnancy and transplacental passages of thyroid hormones is discussed. Diagnosis and management of thyroid dysfunction in pregnancy are updated together with the management of women on thyroid replacement therapy at the time of conception. A practical evaluation of thyroid nodules in pregnancy is suggested. Finally, the syndrome of postpartum thyroid dysfunction is reviewed, stressing the importance of proper diagnosis and the need for long-term follow-up evaluation of these patients. PMID- 7781629 TI - Anaesthesia and microvascular surgery: clinical practice and research. PMID- 7781630 TI - Impact of ischaemia on diastolic function: clinical relevance and recent Doppler echocardiographic insights. PMID- 7781631 TI - The influence of preload on post-systolic shortening in ischaemic myocardium. AB - Post-systolic shortening is a wall motion abnormality defined as shortening of cardiac muscle after the end of ejection and usually regarded as a manifestation of ischaemia. This study was designed to determine whether changes in preload may alter the magnitude of ischaemia-induced post-systolic shortening. Eleven beagles were anaesthetized (halothane 0.8%) and instrumented for measurement of pressures, flows and dimensions in the apical subendocardium supplied by the left anterior descending coronary artery. Myocardial ischaemia was obtained by tightening a micrometer-controlled snare around the left anterior descending coronary artery. Post-systolic shortening, calculated as end-systolic length minus minimum length divided by end-systolic length, was measured at different levels of preload. Increasing the preload from 4 to 17 mmHg caused a significant reduction in post-systolic shortening (8.9% vs. 12.9%, P < 0.05, Student's paired t-test); post-systolic shortening was negatively correlated with coronary perfusion pressure (r = 0.35, P < 0.01) and positively correlated with systolic bulging. This study demonstrates that the amount of post-systolic shortening depends on the volume status, which therefore has to be taken into account in interpreting regional wall motion abnormalities, such as those detected by echocardiography. PMID- 7781632 TI - Continuous spinal anaesthesia versus single dosing. A comparative study. AB - Continuous and single dose spinal anaesthesia were compared in a prospective randomized fashion in 108 patients undergoing orthopaedic surgery. Continuous spinal anaesthesia was via a 20 gauge polyamide multiperforated catheter introduced through an 18 gauge Tuohy needle. Single-dose spinal anaesthesia was performed with a 24 guage x 103 mm Sprotte spinal needle. The mean local anaesthetic dose for the continuous technique was 38.4 (SD 16.5) mg as hyperbaric lignocaine 5%, and for the single-dose spinal anaesthesia 10.8 (SD 2.2) mg as hyperbaric bupivacaine 0.5%. Segmental levels reached with the initial dose did not differ significantly between the two groups. Mean time required to perform continuous spinal anaesthesia was 6.7 (SD 3.9) min, which was longer than for single dose 4.9 (SD 2.8) min (P < 0.05). The onset time and efficacy of anaesthesia, and the duration of the operation were similar in the two groups. Analgesia was inadequate in six patients who received continuous spinal anaesthesia (11%) and one patient who received single dose (2%) (P = 0.18). Hypotension was more frequent in those receiving single doses (P < 0.05). Caudal rotation of the outlet needle orifice to advance the catheter correlated with inadequate analgesia (P < 0.01, r = 0.38). There were no significant differences in the incidence of post-operative complications. PMID- 7781633 TI - The effects of thiopentone, etomidate, ketamine and midazolam on several bactericidal functions of polymorphonuclear leucocytes in vitro. AB - Polymorphonuclear leucocytes (PMNL) are an essential component of the defence system against invading bacteria. There is evidence that some anaesthetics are able to suppress PMNL functions, promoting, perhaps, perioperative infection. We studied the effects of thiopentone, etomidate, ketamine, and midazolam on the generation of bactericidal agents (superoxide anion, hydrogen peroxide, and myeloperoxidase) by PMNL in vitro. Thiopentone inhibited superoxide anion (P < or = 0.01) as well as hydrogen peroxide production (P < or = 0.001). However, there was no statistically significant effect on myeloperoxidase release. Neither etomidate nor ketamine influenced the PMNL functions tested to any extent. Midazolam suppressed superoxide anion generation (P < or = 0.01) but only if a concentration far beyond clinical relevance was used. PMID- 7781636 TI - New technique of sciatic nerve block in the popliteal fossa. AB - A new technique of sciatic nerve block in the popliteal fossa was evaluated in 120 patients using an 18 s.w.g. cannula. Precise placement of the cannula was facilitated with the aid of a nerve stimulator. In addition to an initial dose of 1% prilocaine with adrenaline 1: 200,000 (5 mg kg-1), 5 mL 0.5% bupivacaine was used for blockade of the saphenous nerve distal to the medial tibial condyle. One third or one-quarter of the initial dose was administered when required for augmentation of anaesthesia or post-operative pain relief. Satisfactory anaesthesia was achieved in 117 patients (97.5%); two patients required general anaesthesia, since repositioning of the cannula after initial application of local anaesthetic was strictly avoided. No post-operative complications relating to the nerve block were observed. This technique of sciatic nerve block in the popliteal fossa provides effective and safe anaesthesia of the lower leg. PMID- 7781635 TI - Nitrous oxide with fentanyl and droperidol minimizes lipid peroxidation in the liver. AB - We have studied the level of lipid peroxidation in the liver of rats exposed to nitrous oxide plus oxygen or injected with droperidol of fentanyl. The effect of nitrous oxide used in combination with droperidol and fentanyl was also investigated. All the tested anaesthetics caused lipid peroxidation in the rat liver. It seems likely, however, that the mechanism by which droperidol and fentanyl initiate lipid peroxidation differs from that which nitrous oxide uses. Free radical products and/or activated oxygen species are produced during fentanyl and droperidol metabolism in the liver. However, nitrous oxide is not metabolized in the liver and probably undergoes one electron reduction outside the liver thus producing free radical products and/or activated oxygen species which are able to diffuse and initiate lipid peroxidation in the liver. It was also found that the level of lipid peroxidation in the liver of rats injected with droperidol and fentanyl and then exposed to nitrous oxide was low and close to that of the control animals. We suggest that, when used in combination, the products generated outside the liver as a result of nitrous oxide metabolism are transported to the liver and take part in reactions with the products of the metabolism of droperidol and fentanyl, thus decreasing the concentration of the species able to initiate lipid peroxidation. PMID- 7781637 TI - Mid-latency auditory evoked potentials and wakefulness during caesarean section. AB - We investigated intra-operative wakefulness and mid-latency auditory evoked potentials (MLAEP) in 20 patients undergoing elective Caesarean section under general anaesthesia. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and succinylcholine 1-1.5 mg kg-1 i.v. After delivery, a balanced anaesthetic technique was maintained using fentanyl 0.2-0.3 mg i.v., enflurane 0.4-1.0 vol% end-expired concentration and 50% N2O in oxygen. Purposeful movements were interpreted as signs of inadequate anaesthesia and intra-operative wakefulness. They were recorded as either spontaneous movements or in response to one of two audio tapes (tape A: sound of a crying baby; tape B: classical music). Post operatively, intra-operative dreams, hallucinations and detailed reports about intra-operative events were evaluated. Auditory evoked potentials were recorded online before and during general anaesthesia. Twenty spontaneous purposeful movements were observed in 12 patients, seven before or during delivery and 13 after delivery. Four purposeful movements were observed after presentation of the sound of a crying baby but only one after classical music. Dreams and hallucinations were reported by nine patients. Two patients reported experiencing surgical manipulations. In the awake state MLAEPs had great peak-to-peak amplitudes and a periodic waveform. Under adequate levels of general anaesthesia MLAEPs showed a marked increase in latency and decrease in amplitude or were even suppressed completely. This increase in latencies and decrease in amplitude of MLAEP was absent in patients who reported intraoperative events and during spontaneous or provoked motor reactions. PMID- 7781634 TI - Spontaneous respiration versus controlled ventilation anaesthesia with halothane for intra-ocular surgery. AB - One hundred and thirty-seven patients were randomly allocated to receive halothane anaesthesia for intra-ocular surgery either by IPPV (n = 71) or breathing spontaneously (n = 66). Both techniques provided satisfactory operating conditions in 87% and 80% of procedures, respectively. Intra-ocular pressure was reduced in a similar majority of patients, rose in a similar percentage (spontaneous = 11%, controlled = 21%) and remained unchanged in a few. Surgeons' reports of good operative conditions correlated very well with intra-ocular pressure changes whether they rose or fell intra-operatively. The duration of anaesthesia and the time taken to achieve full recovery following the two techniques were similar. Post-operative vomiting, headache, sore throat and confusion occurred with similar frequency, and analgesic and antiemetic requirements were not influenced by the technique. Resumption of ambulation, oral intake and micturation occurred similarly. In both groups, patients with a low normal pre-operative intra-ocular pressure tended to show a rise in intra-ocular pressure during anaesthesia, and those with a high normal pre-operative intra ocular pressure tended to show a fall. PMID- 7781638 TI - Accidental intravenous administration of 50 mg of racemic adrenaline in a 2-year old boy. AB - A 2-year-old boy received, by mistake, 50 mg racemic adrenaline intravenously, equivalent to 1.8 mg kg-1 of L-adrenaline. The blood pressure increased to 160/105 mmHg, the heart rate to 160 beats min-1, and pulmonary oedema developed over the next 2 h. He was treated with nitroprusside, nitroglycerin and digitoxin, and was intubated and ventilated. After 3 h a hypotensive phase occurred which required infusions of very high concentrations of catecholamines for 72 h. Renal failure required renal transplantation after which the child made an uneventful recovery. PMID- 7781639 TI - Caesarean section in chronic renal failure. AB - A 22-year-old woman presented for Caesarean section at 34 weeks' gestation. She had chronic renal failure, with a glomerular filtration rate of 14 mL min-1 and was treated with twice weekly dialysis. We describe the potential problems of the case including cardiovascular instability, fluid balance and some of the effects of uraemia. We also describe the anaesthetic management of the case. PMID- 7781640 TI - Emergency intubation with the Combitube in two cases of difficult airway management. AB - The airway was managed successfully in two cases of difficult intubation using the Combitube, a new device for emergency intubation, which combines the functions of an oesophageal obturator airway and a conventional endotracheal airway. One patient could not be intubated due to lockjaw; in the other patient, the vocal cords could not be seen because of continued vomiting. The cases illustrate the benefit of the Combitube during emergency intubation for different problems and its effectiveness as an alternative to traditional intubation techniques. PMID- 7781641 TI - Thromboxane A2 receptor antagonist (ONO 3708) protects from liver damage induced by cholestasis and ischemia-reperfusion. AB - The effect of a thromboxane (Tx) A2 receptor antagonist, ONO 3708, on cholestasis and injury related to ischemia and subsequent reperfusion (I-R) was investigated in the dog liver by assessing changes in insulin and glucagon metabolism. The left hepatic duct was ligated for 4 weeks to create a cholestatic lobe. Sixty minute ischemia was induced by Pringle's procedure. ONO 3708 (200 micrograms/kg/min) was initiated 60 min before induction of ischemia and continued throughout the experiment. The rate of insulin metabolism was higher in the right noncholestatic lobe than in the left cholestatic lobe. There was no significant difference in the rate of glucagon metabolism between the right and left lobes. After induction of I-R, the rate of insulin metabolism, but not glucagon metabolism, decreased. The lipid peroxide level was higher and the glutathione level was lower in the cholestatic lobe than in the noncholestatic lobe. There was no significant difference in the alpha-tocopherol level between lobes. After induction of I-R, the lipid peroxide level increased and the alpha tocopherol level decreased. There was no change in the glutathione level. I-R accelerated the release of 6-keto-prostaglandin (PG) F1 alpha, a stable metabolite of PGI2, and of TxB2, a stable metabolite of TxA2, from the liver. After I-R, cholestasis accelerated the release of TxB2, but not 6-keto-PGF1 alpha. I-R also increased the TxB2/6-keto-PGF1 alpha ratio. ONO 3708 reduced these metabolic changes in the cholestasis and after I-R. These findings suggest that ONO 3708 protects liver function, especially in the cholestatic lobe, from I R-related injury by reducing peroxidation of lipids and the TxA2/PGI2 ratio, which predicts cellular damage, and by increasing levels of alpha-tocopherol and glutathione. PMID- 7781642 TI - Effect of cyclosporine A on the demethylation of aminopyrine in rats in vivo. AB - Serial determinations of hepatic function by quantitative tests might provide clinically useful information following liver transplantation provided that the test result is not influenced by the immunosuppressive regimen. To investigate the effect of cyclosporine A with and without prednisolone on established quantitative tests of hepatic function, rats were fed cyclosporine A at a dose resulting in average through blood levels of 1,176 ng/ml, and the aminopyrine breath test which reflects microsomal function, the decarboxylation of ketoisocaproic acid which reflects mitochondrial function and the galactose breath test which reflects cytosolic function were performed at intervals. Cyclosporine A did not impair the demethylation of aminopyrine and the decarboxylation of ketoisocaproic acid in vivo. The metabolism of galactose was enhanced by 25%. The results indicate that in contrast to in vitro experiments, where cyclosporine A has been shown to markedly inhibit the demethylation of aminopyrine and to result in a decrease of cytochrome P-450, therapeutic concentrations of cyclosporine A and prednisolone do not impair aminopyrine demethylation in vivo. Thus, the aminopyrine breath test is a reliable index of hepatic function also in the presence of immunosuppressive treatment. PMID- 7781644 TI - Effect of bile obstruction on liver regeneration following major hepatectomy: an experimental study in the rat. AB - The regeneration of the liver following resection is regulated by a variety of factors and it might be expected that jaundice influences the process. We therefore evaluated the regenerative response to major hepatectomy in bile obstructed rats. Two weeks after ligation of the common bile duct, a standardized 77% hepatectomy was undertaken. The jaundiced animals showed an augmented liver regeneration compared to nonjaundiced individuals (p < 0.01). However, blood clearance of radiolabelled Escherichia coli bacteria was impaired (p < 0.01) in animals with bile obstruction at 7 days after the hepatectomy, accompanied by reduced bacterial uptake in the liver as a sign of impaired reticuloendothelial system function. PMID- 7781643 TI - Effects of oxygen radicals on cysteinyl leukotriene metabolism and pulmonary circulation in young pigs. AB - The effects of oxygen radicals, generated by the hypoxanthine-xanthine oxidase (XO) system, on pulmonary circulation and release of cysteinyl-containing leukotrienes (LTs) were studied in pigs after XO infusion into the right atrium. A 2.3-fold increase in pulmonary vascular resistance (PVR) (p < 0.05 vs. baseline) and a 2.1-fold increase in LT release (p < 0.05 vs. baseline) was observed. Pretreatment with indomethacin and allopurinol attenauted the vascular response (p < 0.01 and p < 0.05 vs. XO), and the LT release was inhibited by allopurinol and catalase (p < 0.01 and p < 0.02 vs. XO). We conclude that oxygen radicals stimulate lipoxygenase metabolism. This coincides with the observed increase in PVR, however, no causal relationship can be derived from the data presented. PMID- 7781645 TI - Improved survival rate after portacaval shunt in the rat using a modified microsurgical technique. AB - It has been observed that portacaval shunt in the rat is accompanied by a high postoperative mortality rate and shunt patency is seldom optimal on long-term follow-up. The immediate postoperative mortality is directly related to the intraoperative duration of occlusion of the portal vein. In order to reduce the intraoperative occlusion time of the portal vein we devised a technique to construct half of the shunt without portal vein occlusion and the other half with occlusion. The total occlusion time was only 4-6 min. There was negligible postoperative mortality and shunt patency was 100% after 6-8 months' follow-up. The changes in body weight, organ weight and metabolic parameters were reproducible. PMID- 7781646 TI - Effect of allopurinol, folinic acid, SOD and cyclosporine A on ischemic liver regeneration. AB - Liver regeneration plays a key role in restoring the liver/body ratio after partial liver transplantation. However, hepatic ischemia hinders the proliferative response of the hepatocytes. In this study, different ways of improving the regenerating capacity of ischemic hepatocytes are tested. Following 70% hepatectomy and 15 min of normothermic liver ischemia, the percentage of regenerating hepatocytes and the regenerative gradient are assessed. Cyclosporine A (hepatotrophic agent), superoxide dismutase and folinic acid (antioxidants), administered during the ischemic period, have significantly increased these indices. The later drug has restored the regenerative response to the levels of normoperfused livers. PMID- 7781647 TI - Deterioration of platelet energy metabolism following energy crisis of liver after hepatectomy. AB - The aim of this study is to investigate the relationship in energy metabolism between the platelet and the liver. The adenylate energy charge of human platelets and arterial ketone body ratio (AKBR:acetoacetate/3-hydroxybutyrate) were measured in 11 patients after hepatectomy. Hepatic energy crisis was defined as the decrease of AKBR below 0.7. The platelet energy charge was measured on the first (Day 1), the second (Day 2), third (Day 3) and sixth (Day 6) day during AKBR decreased and remained under 0.7. The values before AKBR decreased were employed as the control. The values of the platelet energy charge were 0.917 +/- 0.008 in the control (n = 11) and 0.896 +/- 0.009 in all samples after AKBR decreased under 0.7 (n = 30). There was no significant difference between them. The values of energy charge were divided into four groups according to the periods of time after AKBR decreased and remained under 0.7 and compared. The energy charge was 0.923 +/- 0.006 (Day 1, n = 11), 0.907 +/- 0.008 (Day 2, n = 10), 0.890 +/- 0.005 (Day 3, n = 5), and 0.815 +/- 0.012 (Day 6, n = 4). The energy charge of Day 3 was significantly lower than that of Day 1 (p < 0.01). The energy charge of Day 6 was significantly lower than that of Day 1, 2, 3 (p < 0.001, p < 0.001, and p < 0.01, respectively). The 4 patients whose AKBR remained under 0.7 for more than 6 days had hemostatic disorder. The deterioration of the platelet energy charge metabolism lags behind that of the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781648 TI - Haemoglobin saturation in the rat liver after ischaemia and reperfusion: study using a laser photometry technique and correlation with changes in liver tissue blood flow. AB - Tissue oxygenation depends on the volume of oxygen consumed by the tissue and the volume of oxygen supply. This is particularly important in the liver after ischaemia and reperfusion, due to the relatively low oxygen saturation of the portal blood flow, the main source of oxygen to the liver. In this study we established a correlation between the postischaemic liver blood flow and tissue haemoglobin saturation, measured by laser Doppler flowmetry and laser surface photometry, with the purpose of investigating the possible role of a postischaemic imbalance of oxygen delivery/uptake in reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver in vivo, and subsequent reperfusion after defined periods, recording the postischaemic liver blood flow and liver oxyhaemoglobin saturation. Changes were found in the postischaemic liver blood flow and haemoglobin saturation in all the groups when compared to control values, showing a correlation between the length of the period of ischaemia and the magnitude of the alteration in the reperfusion blood flow and oxygenation. These alterations may be considered as a prolongation of the metabolic condition of ischaemia and may be part of an additional tissue damage upon reperfusion. PMID- 7781649 TI - Effect of growth hormone on hepatic energy metabolism in normal rabbit liver. AB - Growth hormone (GH), which is well known as an anabolic agent in systemic protein metabolism but has catabolic effects on the carbohydrate metabolism in the liver, was administered to normal rabbit to investigate its effects on the hepatic energy metabolism. The changes in arterial ketone body ratio (AKBR: acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial redox state ([NAD+]/[NADH]), after GH injection was studied as an indicator of the hepatic energy metabolism. GH was administered to normal rabbit at the doses of 50 micrograms/kg (GH-50 group), 100 micrograms/kg (GH-100 group) and 200 micrograms/kg (GH-200 group) by intravenous bolus injection. In the GH-50, GH-100 and GH-200 groups, AKBR decreased significantly from 1.40 +/- 0.09 to 0.94 +/- 0.05, from 1.19 +/- 0.11 to 0.83 +/- 0.14, and from 1.19 +/- 0.08 to 0.71 +/- 0.15 at 90 min, respectively. The energy charge of the liver decreased significantly 90 min after 200 micrograms/kg GH injection from 0.872 +/- 0.003 to 0.836 +/- 0.012 (p < 0.05). These results suggest that GH is associated with the deterioration of the hepatic energy metabolism, and that the administration of GH should be carefully weighed up in cases of damaged liver. PMID- 7781650 TI - Dynamic liver scintigraphy: a new way of measuring the function of the reticuloendothelial system of the liver. AB - The phagocytic function and biokinetics of the hepatic reticuloendothelial system (RES) were evaluated using a 25-nm diameter colloid (Nanocoll) and a scintillation camera technique in opossums with obstruction of the pancreatic duct (group I) and additional obstruction of the common bile duct (group II). The liver net uptake curve was analysed using natural log regression. The regression curves proved to fit very well (r > 0.93) and a parameter R was calculated to describe the curves. In group I there was a slight but significant decrease in the RES function and no morphological change in the pancreas. In group II, RES function was significantly more suppressed than in group I. The opossums developed severe haemorrhagic pancreatitis. The results show that the regression parameter R is well suited to described liver RES function, and suggest that a suppressed liver RES after biliary obstruction could be an important factor in the pathogenesis of biliary pancreatitis. PMID- 7781651 TI - Rapid determination of the membrane potential of mitochondria in small biopsy specimens of the liver. AB - In liver transplantation, graft viability is ideally to be determined before implantation. Integrity of mitochondria may be a prerequisite to a viable graft. A new method is presented, which allows for the determination of the membrane potential of mitochondria (MPM; mV) in state 4 respiration within 50 min in 40-mg specimens, employing rhodamine 123 as a probe. Normal control showed a MPM of 239.2 mV. Storage in saline at 37 degrees C yielded an impaired MPM of 153.5 mV within 3 h. The cold storage at 1 degree C could preserve MPM at quasi-normal after 3 h but reduced it significantly after 24 h to 222.2 mV in saline (p < 0.005 vs. control) and 231.0 mV in UW solution (p < 0.05 vs. control): the difference between the 24-hour values was significant (p < 0.05). PMID- 7781652 TI - Segmental organization of the pig liver: anatomical basis of controlled partition for experimental grafting. AB - Segmental anatomy has been investigated on 54 pig livers by bench-top radiology and ultrasonography of hepatic and portal vessels and bile ducts and dissection of suprahepatic veins. Eight segments were recognized, homologous to those of the human liver. Major variations were found only of arterial distribution. The inferior vena cava invariably ran within the parenchyma of the right lobe and close to the liver hilum; suprahepatic veins were also entirely intraparenchymal. Therefore, the pig liver can easily be divided into two halves, but only the right one can be used for reduced-size grafting into a recipient. PMID- 7781653 TI - Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. AB - This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars. PMID- 7781655 TI - The backflow from the pulmonary circulation for identification of the aortic origin of the bronchial arteries in experimental left single lung transplantation. AB - The ideal solution to the bronchial healing problems in lung transplant would be the reconstruction of the bronchial arteries at time of transplantation. The problems with this approach are essentially technical being difficult to identify and preserve the bronchial arteries in humans. The purpose of this paper is to report our experience with an experimental model in dog to easily identify and preserve bronchial circulation in single lung transplantation. The technique is based on the preservation during harvesting of the aortic origin of the first five couples of arterial orifices. Identification of the orifice(s) connected with the bronchial circulation is carried out by the backflow which takes place from the pulmonary circulation after organ reperfusion is resumed. The identified orifice(s) is then anastomosed to the descending recipient aorta, tangentially clamped. PMID- 7781654 TI - Successful long-term cryopreservation of highly purified canine islets. AB - This study evaluated the ability of cryopreservation to store large quantities of canine islets for transplantation studies. Islets were isolated by automated screen methods and purified by Euro-Ficoll gradients. After overnight 37 degrees C incubation, islets were equilibrated with 2 M dimethylsulfoxide, cryopreserved at a cooling rate of 0.25 degree C/min and subjected to long-term storage in liquid nitrogen. Six months later, some islets were thawed at a rate of 180 degrees C/min. The viability of cryothawed islets was determined in vitro by comparing islet count, total insulin content, morphology and perifusion studies in both control and cryothawed islets, and in vivo by transplantation into diabetic nude mice. The percentages of recovery of both islet count and total insulin content were 74.17 +/- 4.46 and 70.66 +/- 14.08, respectively. Islet morphology after cryothaw by light and electron microscopy revealed structurally intact islets with varying degrees of granulation. The results of perifusion indicated that there was no significant difference (p > 0.1) in both total stimulated insulin secretion and stimulation index response to high-dose glucose plus 3-isobutyl-1-methylxanthine and carbachol of isolated islets as compared to those of cryothawed islets. Transplantation into nude mice proved that grafted islets can successfully reverse diabetes. In conclusion, these findings indicate that the majority of purified canine islets can survive the frozen-thawed insult while maintaining their secretory function and permitting mass storage of canine islets for further transplant studies. PMID- 7781656 TI - Heparin effects on superoxide production by neutrophils. AB - Heparin is widely used in the treatment of various diseases, but the mechanisms of its biologic actions remain largely obscure. Recently, oxygen radicals, which are produced in a variety of conditions and cause tissue damage, have been implicated in the pathophysiology of various diseases. To investigate the relationship between heparin and oxygen radical production by neutrophils, we compared the effects of standard heparin (heparin sodium), which has been widely used, and a recently developed low molecular weight heparin (LMWH) which has potent anti-Xa activity, on neutrophil oxygen radical production in vitro. Standard heparin increased neutrophil oxygen radical production slightly at the low concentrations used clinically but reduced it at high concentrations, so that the effect of heparin on neutrophil oxygen radical production was biphasic. The effects of LMWH on neutrophil oxygen radical production were slight at both low and high concentrations. In disseminated intravascular coagulation (DIC) locally activated neutrophils produce oxygen radicals and have toxic effects in vivo. Thus we concluded that LMWH should be indicated for the treatment of DIC. PMID- 7781657 TI - Effect of allogeneic polymorphonuclear neutrophils on staphylococcal sepsis in mice. AB - The antibacterial and host-damaging properties of locally injected allogeneic polymorphonuclear neutrophils (PMN) were studied in vivo. Peritoneal PMN were obtained from donor mice 24 h after i.m. infection with sublethal (SD) and lethal (LD) dose of Staphylococcus aureus. These donor PMN were mixed with S. aureus and injected i.m. into normal recipient mice. Normal donor PMN and PMN obtained from SL-infected donor mice did not induce the mortality of SL-infected recipient mice but protected LD-infected recipients (5.8% mortality vs. 29.4%). PMN obtained from LD-infected donor mice caused ca. 77% mortality in SD-infected recipients. In survivors, during the first 3 h infection, serum tumor necrosis factor (TNF) concentrations were higher than those in nonsurvivors and then decreased. In contrast, TNF level in nonsurvivors continued to be increased until death. PMN from LD-infected donors had the highest spontaneous chemiluminescence response (CL), the shortest time of peak and the lowest level of intracellular CL against S. aureus. These donor PMN exhibited increased phagocytosis and decreased killing of S. aureus than that of PMN of SD-infected donor mice. Early stimulation of PMN functions such as bacterial internalization and respiratory burst may result in decrease of their tissue-damaging properties. PMID- 7781658 TI - Changes in intraosseous pressure at the distal femoral epiphysis induced by variations in knee-joint position and intracapsular saline infusion. An experimental study in dogs. AB - Hemodynamic changes at the distal femoral epiphysis measured by recording intraosseous pressure (IOP) were investigated in mature and juvenile dogs after changes in knee-joint position and intracapsular infusion of 3 ml isotonic saline solution. Juvenile and mature animals responded to infusion test with a similar 5 fold increase in intracapsular pressure. A 2-fold increase in IOP was found when knee-joint flexion passed from 30 degrees to complete flexion. In juvenile dogs, IOP values were lower than in adults both in complete knee flexion and during infusion test. The similar response to joint hyperpressure tests observed in adult and juvenile dogs suggests that the barrier effect of the growth plate for epiphyseal venous drainage has no major influence in the hemodynamics of the distal femoral epiphysis. PMID- 7781659 TI - The lipoprotein composition of plasma and ascitic fluid in liver cirrhosis. AB - Lipoprotein particles were examined in plasma and ascitic fluid from nine patients (5 males and 4 females) with liver cirrhosis and in plasma from nine control subjects. LDL and HDL fractions were isolated by ultracentrifugation under rate flotation conditions in a zonal rotor. LDL size was analysed by non denaturing polyacrylamide gradient gel electrophoresis. Plasma lipids in cirrhotic patients were markedly reduced compared to controls. Free cholesterol represented 45.3% of the total cholesterol in plasma and 70.4% of the total cholesterol in the ascitic fluid. The total cholesterol-triglyceride ratio was three times higher in the plasma than in the ascitic fluid of cirrhotic patients. The LDL particles had the same flotation properties in plasma from cirrhotic patients as in that from controls. In cirrhotic patients the IDL concentration was higher than that in controls. In ascitic fluid the LDL particles had a higher flotation rate than in the plasma. The LDL diameter as measured by gradient gel electrophoresis was similar in both plasma and ascitic fluid of the cirrhotic patients as well as in the plasma of controls. In plasma and ascitic fluid of cirrhotic patients only a single HDL subclass (HDL1) could be identified. HDL1 particles had a higher flotation rate than normal HDL particles. The plasma levels of all the apoproteins were reduced in cirrhotic subjects compared to controls, but to a variable degree; while apo CII level in cirrhosis represented only 9% of the control level, the apo E level represented 77% of the control level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781660 TI - Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinaemia. AB - The pathobiochemical mechanism of arteriosclerosis in hyperhomocysteinaemia has not yet been elucidated. In vitro studies have shown that the cytotoxic properties of homocysteine can be ascribed to its generation of reactive oxygen species. We studied lipid peroxidation, both in vivo and in vitro, in 10 homozygous cystathionine synthase-deficient (CSD) patients and in a control group of 10 healthy subjects of comparable age and sex. The susceptibility of low density lipoprotein (LDL) from hyperhomocysteinaemic patients to oxidation was determined in vitro by continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time needed to reach maximal diene production, i.e. t(max), was similar for LDL from patients and controls. In addition, the vitamin E concentrations in LDL of CSD patients and controls were similar. The mean concentration (+/- SD) of plasma thiobarbituric acid reactive substances (TBARS), an indicator of in vivo lipid peroxidation, was 2.2 +/- 0.7 mumol L-1 in CSD patients, a lower value than that measured in the matched controls (5.0 +/- 2.0 mumol L-1). Investigation of in vivo and in vitro parameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to increased lipid peroxidation. PMID- 7781661 TI - Phenotypic and immunoregulatory analysis of intestinal T-cells in patients with inflammatory bowel disease: evaluation of an in vitro model. AB - Although a disturbed immune response to constituents of the gut mucosa has been implicated in the pathogenesis of inflammatory bowel disease, the mechanisms are still unclear. Intestinal T-cells derived from gut biopsies were propagated in vitro as single and co-cultures under different experimental conditions prior to flow cytometry. Intestinal T-cell lines from inflamed mucosa (n = 69) showed a significant (P < 0.001) decrease in CD4+ T-cells compared to T-cells from normal (n = 49) and uninflamed (n = 29) tissue specimens. Co-culturing of inflamed and uninflamed mucosa led to a normalization of CD4+ T-cells in cultures derived from inflamed mucosa. Analysis of supernatants revealed a significantly (P < 0.001) increased secretion of IL-4 under co-culture conditions. Moreover, stimulation of cultures derived from inflamed mucosa with rIL-4 led to a significant (P < 0.001) increase in CD4+ T-cells, whereas anti-IL-4 antibodies or IFN-gamma supplementation of T-cells derived from uninflamed mucosa significantly (P < 0.001) reduced the CD4+ subset. Treatment with IFN-gamma and anti-IL-4 antibodies did not affect the phenotype of T-cells derived from inflamed mucosa. These data suggest that IL-4 might play a key role in the intestinal immune response. Furthermore, this in vitro system allows the investigation of mucosal immune mechanisms in more detail under standardized conditions. PMID- 7781663 TI - Prolonged consumption of moderate doses of alcohol and in vitro gastro-duodenal and ileal contractility in the rat. AB - The effects of chronic feeding with moderate doses of ethanol (3% vol/vol in drinking water for 8 weeks), which do not induce tolerance, dependence and withdrawal, on the contractility of gastric, duodenal and ileal strips from rats were investigated. Only 50% of ethanol-treated specimens (as compared to 100% of saccharose-fed controls) exhibited antral phasic contractions (frequency decreased by 31% and 27% in the antrum and duodenum, respectively; P < 0.03 vs. controls). The depolarizing agent potassium chloride (KCl, 80 mM) produced less peak active tension in the fundus of ethanol-fed rats (P < 0.01). In alcoholic rats the sensitivity of the antrum to acetylcholine was fourfold less than that of control specimens. It is concluded that, in the rat, moderate doses of ethanol given chronically impair both spontaneous and tonic contractility of the stomach and duodenal muscle without affecting ileal contraction. It is possible that motility defects in the gut exposed to ethanol concentrations which do not cause tolerance, dependence or withdrawal in the rat may be due to a local rather than a systemic effect on the smooth muscle. PMID- 7781662 TI - Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake. AB - Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition. PMID- 7781665 TI - Response of digital arteries to endothelium dependent and independent vasodilators in patients with Raynaud's phenomenon. AB - The cause of the digital artery spasm seen in Raynaud's phenomenon (RP) is unclear. A dysfunction of endothelium-dependent vasodilation might contribute to the development of this spasm. We studied the digital artery responses to endothelium-dependent and independent vasodilators in eight Raynaud's phenomenon patients and eight sex-matched controls. A sequential series of infusions alternating with physiological saline were administered at a rate of 1 mL min-1 via the radial artery. The infusions contained acetylcholine chloride (ACh) 110 nm mL-1 and 550 nm mL-1, L-arginine 50 mumol mL-1, prostacyclin (PGI2) 2.5 ng mL 1 and glyceryl trinitrate (GTN) 4.5 nm mL-1. Digital artery diameter (DAD) and cutaneous temperature were measured. DAD was measured using a high frequency A mode ultrasound scanner. There was no significant difference in mean brachial artery pressure, digital cutaneous temperature and DAD between the two groups at the start of the study. Comparing responses in the groups, there was a significantly greater increase in DAD and cutaneous temperature to Ach (endothelium-dependent vasodilator) at both concentrations in controls. A significantly greater increase in DAD was obtained in response to GTN (endothelium-independent vasodilator) in the RP subjects. There was no significant difference in response to L-arginine and PGI2 between the groups. These results suggest that a dysfunction of endothelium-dependent vasodilation is present in RP patients. PMID- 7781664 TI - Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. AB - Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction. PMID- 7781666 TI - Radioiodine therapy of Graves' hyperthyroidism: standard vs. calculated 131iodine activity. Results from a prospective, randomized, multicentre study. AB - The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq 131iodine vs. an activity calculated to deliver 100 Gy for treatment of Graves' thyrotoxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radioiodine application (range 4.5-8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for both approaches, but only in retrospective investigations. Investigated prospectively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic success was inversely related to thyroid size. The rate was 100% for thyroid volumes < or = 15 mL, 95% for 16-30 mL, 68% for 31-45 mL, 44% for 46-50 mL, 20% for 61-75 mL and 25% for > or = 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume < or = 15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11% for a target dose of 50 Gy, 50% for 100 Gy, 67% for 150 Gy, 80% for 200 Gy, 84% for 250 Gy, 88% for 300 Gy, 90% for 350 Gy and 93% for 400 Gy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781668 TI - Veno-arterial carbon dioxide and pH gradients and survival in critical illness. AB - Recent studies have shown that the veno-arterial gradient for carbon dioxide (dVApCO2) is increased in the case of low cardiac index (CI). In order to further investigate this matter 220 haemodynamic measurements from 34 patients with septic shock and from 28 patients in the post-operative state without sepsis were evaluated. The arteriovenous gradient for pH (dAVpH) was also evaluated. CI was found to be inversely correlated to both dVApCO2 and dAVpH when the two groups of patients were analysed separately (r = -0.76 and r = -0.78, P < 0.001 for the relationship between CI and dVApCO2, r = -0.58 and r = -0.69, P < 0.001 for the relationship between CI and dAVpH). When volume loading over 2h was used to increase CI, 58-66% of the patients in the two groups showed a decline in dVApCO2 > 10% when CI was increased by > 10%. The corresponding values for a reduction in dAVpH > 10% during volume loading was 36-52%. While dAVpH was found to be increased in non-survivors (n = 27) when compared to survivors (0.32 +/- 0.01 vs. 0.24 +/- 0.1, P < 0.05) at the second day in the IUC, dVApCO2 was not a significant predictor of mortality despite the fact that CI was found to be decreased in the non-survivors (3.5 +/- 0.94 vs. 4.3 +/- 1.0 L min-1 m-2, P < 0.01). In conclusion, the veno-arterial carbon dioxide gradient was found to be inversely correlated to cardiac performance in patients both in patients with septic shock and in non-septic post-operative patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781667 TI - Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes. AB - In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non-insulin dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L-1, range 15-1550 mg L-1 vs. 157 mg L-1, range 15-919 mg L 1, NS and 92, range 15-1190 mg L-1 vs. 103 mg L-1, range 15-842 mg L-1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg L-1, but this effect was not related to the concomitant improvement in metabolic control (mean change (+/- SEM) of HbA1c from 9.80 +/- 0.15 to 8.00 +/- 0.12; P < 0.001). In subjects with elevated Lp(a) concentrations (> 300 mg L-1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may modulate the concentration of Lp(a). PMID- 7781670 TI - CCK-A antagonists: which and how. PMID- 7781669 TI - Human neutrophil and plasma endopeptidase 24.11: quantification and respective roles in atrial natriuretic peptide hydrolysis. AB - Neutral endopeptidase 24.11 activities were quantified on human peripheral blood cell preparations (reflecting the enzyme concentration on the surface of neutrophils) and in the corresponding diluted plasmas by a spectrofluorimetric assay. Despite statistically identical values in both compartments, enzymatic activity towards atrial natriuretic peptide was not comparable. Indeed, incubation of the radiolabelled peptide in whole blood resulted in the thiorphan sensitive production of the labelled metabolites Phe-Arg-Tyr and the Cys-Phe bond cleaved peptide. A similar degradation pattern was observed for blood cells but not for plasma, providing evidence for the exclusive involvement of neutrophil endopeptidase in this peptide inactivation. In search for plasma component(s) susceptible to inhibit enzymatic activity, we observed that in the presence of alpha 2-macroglobulin at the physiological concentration of 3.5 mg mL-1, endopeptidase activity decreased from 100% to 51.2 +/- 8.9% (P = 0.002). Our data suggest that this protein could play a role in the endogenous inhibition of plasma endopeptidase activity. PMID- 7781671 TI - Definition and localization of histamine H2 receptors. PMID- 7781672 TI - In vitro effects of H2-receptor antagonists on the cardiovascular system. PMID- 7781673 TI - Cardiac effects of amthamine: a new histamine H2-receptor agonist. PMID- 7781674 TI - Value of different methods for characterizing cardiovascular drug effects. PMID- 7781675 TI - Systolic time intervals: a method to assess cardiovascular drug effects in humans. PMID- 7781676 TI - Haemodynamic profile of new H2-receptor agonists in congestive heart failure. PMID- 7781677 TI - Clinical aspects of cardiovascular effects of H2-receptor antagonists. PMID- 7781678 TI - Evan's blue dye blocks capsaicin-induced cough and bronchospasm in the guinea pig. AB - The influence of Evan's blue dye on capsaicin-induced bronchoconstrictor and cough responses was investigated in the guinea pig. Evan's blue (30 mg kg-1 i.v.) pretreatment shifted the bronchoconstrictor dose-response to capsaicin (0.3-100 micrograms kg-1 i.v.) to the right by 10-fold, but had no effect on the bronchospasm elicited by neurokinin A (0.3-10 micrograms kg-1 i.v.). Evan's blue (0.3-30 mg kg-1 s.c.) also inhibited capsaicin-induced cough in a dose-dependent manner. Evan's blue blocked capsaicin responses by the intravenous, subcutaneous, or inhaled routes of administration. We conclude bronchoconstrictor responses and cough in vivo. PMID- 7781680 TI - Effects of methylnaltrexone on morphine-induced inhibition of contraction in isolated guinea-pig ileum and human intestine. AB - We investigated the effects of methylnaltrexone on morphine-induced inhibition of smooth muscle-strip contraction in isolated guinea-pig ileum and human small intestine. The longitudinal muscle-strip was immersed in a temperature-controlled (37 degrees C) bath containing a physiological solution of 95% O2 and 5% CO2 with pH 7.4. Muscle contraction was elicited by transmural electrical stimulation with a pulse duration of 0.5 ms at frequencies of 1-50 Hz for 5-10 s at 1-3-min intervals. Muscle contraction was blocked by tetrodotoxin or atropine in both preparations. When methylnaltrexone was applied to the bath, the force produced by muscle contraction was enhanced up to approximately 30%. Stimulation-elicited muscle contraction was inhibited by morphine, which decreased the force of contraction 42 +/- 9.5% (S.D.) in the human intestine preparation and 35 +/- 8.6% in guinea-pig ileum at the inhibitory concentration 70% (IC70). Methylnaltrexone effectively antagonized the effects of morphine-induced inhibition of muscle strip contraction. In the guinea-pig ileum preparation, methylnaltrexone at 30, 100 and 300 nM blocked 25 +/- 10.5%, 74 +/- 7.2% and 89 +/- 9.9% of morphine induced (300 nM) inhibition, respectively. In the human intestine preparation, methylnaltrexone at the same concentrations blocked 57 +/- 10.9%, 74 +/- 12.9% and 92 +/- 7.2% of morphine-induced (100 nM) inhibition, respectively. The relative ratio of methylnaltrexone to morphine was higher in human intestine (1:1) than in the guinea-pig ileum preparation (1:3). These data provide preliminary information for clinical studies to evaluate the efficacy of methylnaltrexone in preventing or reducing morphine-induced antimotility and antitransit actions. PMID- 7781679 TI - 7-Oxo-prostacyclin affects the electrogenic Na+/K+ pump in mouse diaphragm fibers. AB - The effect of a stable prostacyclin derivative, 7-oxo-prostacyclin, on the electrogenic Na+/K+ pump in mouse diaphragm muscle was investigated. Resting membrane potentials of muscle cells were measured with glass microelectrodes. In fresh diaphragm preparations from 7-oxo-prostacyclin-pretreated mice (50 micrograms.kg-1 7-oxo-prostacyclin i.p. 30-34 h prior to the experiment) resting membrane potentials were significantly higher (-83.86 +/- 1.40 mV, mean +/- S.E.M.) than in control preparations (-70.78 +/- 1.07 mV). Ouabain at a concentration of 10(-4) mol.l-1 abolished this hyperpolarization (P < 0.05). The electrogenic effect induced by addition of 5 mmol.l-1 K+ to Na(+)-loaded muscles from 7-oxo-prostacyclin-pretreated animals was also enhanced (delta resting membrane potential = 21.73 +/- 3.13 mV) compared with that of the controls (delta resting membrane potential = 18.36 +/- 1.29 mV). Ouabain antagonized the increase in electrogenicity of Na(+)-loaded diaphragms induced by 7-oxo-prostacyclin pretreatment (P < 0.05). In contrast to control preparations, no inhibition of the electrogenic effect induced by 10 mmol.l-1 Ca2+ ions in Na(+)-loaded muscles was observed in diaphragms from 7-oxo-prostacyclin-pretreated animals. In acute experiments with Na(+)-loaded muscles, where 10(-7) mol.l-1 7-oxo-prostacyclin was added to the bath, resting membrane potential reached up to -100 mV. The electrogenic pump-induced increase in resting membrane potential amounted to approximately 30 mV. This effect could be also abolished by 10(-4) mol.l-1 ouabain (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781681 TI - Evidence for atypical endothelin receptors and for presence of endothelin converting enzyme activity in the mouse isolated vas deferens. AB - The endothelin receptors controlling sympathetic neurotransmission and the presence of endothelin-converting enzyme were investigated in the mouse vas deferens. Endothelin-1 or endothelin-3 (0.01-100 nM) enhanced contractions evoked by field stimulation, yielding EC50 (geometric mean and 95% confidence limits) of 0.7 nM (0.4-1.6) and 13.7 nM (10.2-14.1) and Emax (mean +/- S.E.M. increase in twitch tension, in mg/10 mg wet tissue) of 473 +/- 35 and 520 +/- 51, respectively. The selective endothelin ETB receptor agonists IRL 1620 (Suc [Glu9,Ala11,15]endothelin-1) and sarafotoxin S6c were inactive up to 100 nM. Responses to endothelin-3 were progressively inhibited by the selective endothelin ETA receptor antagonist BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) (10, 30 and 100 nM). At 100 nM, BQ-123 almost abolished the response to endothelin-3 (100 nM). In contrast, at 100, 300 nM and 1 microM, BQ-123 shifted the curve to endothelin-1 to the right only 2-, 5- and 6-fold, respectively. The selective endothelin ETB receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L gamma-methyl-leucyl-D-1-++ +methoxycarbonyltryptophanyl-D-norleucine) (100 nM) did not modify responses to endothelin-1 or endothelin-3 (0.01-100 nM). Big endothelin-1 (0.3-30 nM) was 10-fold less potent than endothelin-1 in increasing neurogenic responses (EC50 6.8 nM, 4.7-9.6; Emax 457 +/- 37 mg/10 mg wet tissue). Preincubation with phosphoramidon (100 microM) reduced responses to big endothelin-1, but not endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781682 TI - Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice. AB - The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl) 1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception. PMID- 7781683 TI - Effects of purinoceptor agonists on smooth muscle from hypertrophied rat urinary bladder. AB - Tension responses induced by the purinoceptor agonists ATP and the stable ATP analogue alpha, beta-methylene ATP were investigated in isolated muscle strips from normal and hypertrophic urinary bladders from the rat. Hypertrophy was induced by a partial ligation of the urethra giving an increase in mean bladder weight from 65 mg to 300 mg. Activation with ATP and alpha, beta-methylene ATP caused phasic, concentration-dependent, contractions. The sensitivity to ATP was about 100-fold lower than that for alpha, beta-methylene ATP. The force of the contractions induced by the purinoceptor agonists was significantly lower in the hypertrophied bladder compared to the controls. The kinetics of the ATP-induced responses was studied by photolytic release of ATP from caged-ATP in intact fibre bundles. The rate of contraction following photolytic release of ATP was slower, and the force amplitude lower, in the hypertrophic preparations compared to the controls. The results suggest changes in the purinoceptor function or in the responses of the contractile system to transient increases in intracellular Ca2+ in the hypertrophic bladder. PMID- 7781684 TI - Benzodiazepines and peptides stimulate pregnenolone synthesis in brain mitochondria. AB - Mitochondria isolated from rat brain were found to cleave cholesterol to produce pregnenolone, the precursor for hormonal steroids, at a mean rate of 21.0 pmol pregnenolone.mg protein-1.min-1. This rate-limiting step in steroidogenesis was significantly stimulated by PK 11195 (1-(2-chlorophenyl)-N-methyl-(1 methylpropyl)-3-isoquinoline carboxamide) and Ro5 4864 (4'-chlorodiazepam), ligands which bind to peripheral benzodiazepine receptors with high affinity. Low affinity ligands for the peripheral benzodiazepine receptor such as Ro15 1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5 alpha][1,4] benzo-3 carboxylate) and clonazepam had no significant effect on the rate of pregnenolone synthesis. Furthermore, the rank order of potency of these compounds as inhibitors of [3H]Ro5 4864 binding was identical to the rank order for steroid production. Since the 86-amino acid peptide diazepam binding inhibitor is also thought to bind to the peripheral benzodiazepine receptor, four fragments of this peptide, a random sequence and steroidogenesis activator peptide were also evaluated for their ability to interact with peripheral benzodiazepine receptors and to stimulate steroidogenesis in rat brain mitochondria. Steroidogenesis activator peptide and two fragments of diazepam binding inhibitor significantly stimulated pregnenolone biosynthesis. In contrast to the peripheral benzodiazepine receptor ligands, no correlation between peptide potency in displacing [3H]Ro5 4864 binding and steroidogenesis was observed. PMID- 7781685 TI - Induction but not expression of behavioural sensitization to nicotine in the rat is dependent on glucocorticoids. AB - Behavioural sensitization has been implicated in the development of addictive behaviour, and several studies suggest that corticosteroids may be involved in this phenomenon. In the present study, the effects of adrenalectomy and steroid replacement treatments on the behavioural sensitization observed after daily injections of nicotine (0.4 mg/kg s.c.) were investigated in the rat. Adrenalectomy completely prevented sensitization to the locomotor stimulating effect of nicotine after repeated injections but did not influence the acute locomotor activating effect of the drug or an already established sensitization to nicotine. In adrenalectomized animals receiving replacement treatment with corticosterone or dexamethasone, but not aldosterone, repeated administration of nicotine produced behavioural sensitization. Repeated dexamethasone treatment per se failed, however, to sensitize rats to nicotine. Post mortem neurochemical studies showed that repeated administration of nicotine significantly increased homovanillic acid (HVA) levels, as well as the dihydroxyphenylacetic acid (DOPAC)/dopamine quotient, in the limbic forebrain. Adrenalectomy per se significantly increased HVA levels and tended to elevate the DOPAC/dopamine quotient. When repeatedly treated with nicotine, adrenalectomized rats displayed a higher DOPAC/dopamine quotient, but no significant difference in HVA levels, compared to nicotine-treated sham-operated controls. In the striatum and the cortex, no significant effects of nicotine treatment or adrenalectomy were observed on any of the neurochemical measures. The present results suggest that glucocorticoid (type II) receptor activation is required for induction of sensitization to the locomotor stimulatory effect of nicotine, whereas corticosteroids are not required for the expression of the behavioural sensitization once established. Provided that HVA levels and the DOPAC/dopamine quotient relatively well reflect the presynaptic dopamine activating effect of nicotine, it may be suggested that corticosteroid-related mechanisms associated with behavioural sensitization to nicotine are post- rather than presynaptically located in relation to mesolimbic dopamine neurons. PMID- 7781686 TI - Gastric mucosal protection by YM638, a novel leukotriene D4 receptor antagonist, in rats. AB - YM638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl] thio]-1,3,4-thiadiazol 2-yl]thio] acetic acid) is a novel leukotriene D4 receptor antagonist. We investigated the involvement of the leukotriene D4 receptor blocking activity of YM638 in the gastric mucosal protection of this drug in rats. YM638 significantly prevented gastric lesion formation induced by water-immersion restraint stress, indomethacin, absolute ethanol, 0.7 N HCl and the combination of 0.2 N HCl and hemorrhagic shock, with ED50 values of 26.4, 4.1, 4.7, 35.4 and 8.0 mg/kg p.o., respectively. Cetraxate and sofalcone showed inhibitory effects on most of these gastric lesions, but the inhibitory effects of these compounds were much weaker than those of YM638. In contrast, YM638 had no effect on gastric acid secretion and gastric lesion formation in pylorus-ligated rats, or on duodenal lesion formation in cysteamine-administered rats. YM638 competitively antagonized leukotriene D4-induced contraction of the isolated stomach, with a pA2 value of 7.63 +/- 0.18. In anesthetized rats, intravenous YM638 inhibited leukotriene D4 induced aggravation of gastric lesions caused by HCl, and leukotriene D4 and HCl induced reduction of the potential difference. In addition, oral YM638 significantly increased gastric mucosal blood flow and prevented ethanol-induced increase in gastric vascular permeability. Endogenous prostaglandins, sulfhydryls and nitric oxides were not involved in this inhibitory effect on absolute ethanol induced gastric lesion. YM638 did not react with the stable free radical 1,1 diphenyl-2-picrylhydrazyl in vitro, indicating that YM638 does not have potential as free radical scavenger. These results suggest that the preventive effect of YM638 on gastric lesions is attributable not only to its leukotriene D4 receptor blocking activity but also to the activation of gastric mucosal defensive mechanisms such as mucosal blood flow and vascular permeability. PMID- 7781687 TI - Effect of JTP-2942, a novel thyrotropin-releasing hormone analogue, on pentobarbital-induced anesthesia in rats. AB - The effects of a novel thyrotropin-releasing hormone (TRH) analogue, N alpha ((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-pro linamide monohydrate (JTP-2942), on pentobarbital-induced anesthesia in rats were investigated and compared with those of TRH. Intravenous administration of both JTP-2942 and TRH caused a dose-dependent decrease in the recovery time from pentobarbital-induced anesthesia. The minimum effective doses of JTP-2942 and TRH were respectively 0.03 and 1 mg/kg. The effect of JTP-2942 was antagonized by intraperitoneal scopolamine (0.5 mg/kg). Intraperitoneal JTP-2942 (1 mg/kg) caused an increase of acetylcholine release and a decrease of choline release in the frontal cortex and hippocampus of pentobarbital-treated rats. In addition, JTP-2942 ameliorated the decrease of hemicholinium-3-sensitive high-affinity choline uptake and the increase of acetylcholine in these brain regions. However, JTP-2942 had no effect on choline acetyltransferase activity or the choline content, which were also not changed by pentobarbital. Our results indicate that the effect of JTP-2942 on pentobarbital-induced anesthesia was about 30 times more potent than that of TRH, and suggest that JTP-2942 may act by accelerating acetylcholine turnover. PMID- 7781688 TI - 5-Carboxamidotryptamine attenuates the development of deoxycorticosterone acetate salt hypertension in rats. AB - The effect of chronic i.v. infusion of the 5-HT1 receptor agonist, 5 carboxamidotryptamine (5-CT), was evaluated during the development of deoxycorticosterone acetate-salt (DOCA-salt) hypertension in rats over 4 weeks. Vehicle-treated (n = 10) Sprague-Dawley rats given DOCA (100 mg/kg, s.c.) and 1% saline as drinking fluid developed hypertension with systolic blood pressure reaching 194.6 +/- 8.99 mm Hg at 27 days. In DOCA-salt rats treated with 5-CT infusions (15.0 micrograms/kg per day, n = 10) for 4 weeks via osmotic minimpumps, systolic blood pressure was significantly lower by 41.7 mm Hg at day 27 when compared to vehicle-treated DOCA-salt rats. Systolic blood pressure values on day 27 in 5-CT-treated DOCA-salt rats were however greater than those in vehicle-treated control rats which were not given DOCA. Systolic blood pressure in 5-CT-treated DOCA-salt rats was significantly lower by day 7 compared to vehicle-treated DOCA-salt rats and remained lowered for the rest of the observation period. Heart rate was significantly greater in 5-CT-treated DOCA salt rats on day 7 when compared to vehicle-treated DOCA-salt rats. Baroreflex sensitivity on day 28 was significantly greater in 5-CT-treated DOCA-salt rats as compared to vehicle-treated DOCA-salt rats. On day 28, hypotensive responses to hexamethonium (20 mg/kg) in 5-CT-treated DOCA-salt rats were markedly reduced compared to those in vehicle-treated DOCA-salt rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781689 TI - Cocaine promotes an apparent direct vasoconstrictor effect of neuropeptide Y in the rat tail artery. AB - Neuropeptide Y is a powerful vasoconstrictor in vivo; however, in vitro it shows weak constrictor effects. This discrepancy may have led to conflicting reports concerning the contractile effects of neuropeptide Y on isolated blood vessels. Using isolated rat tail and femoral artery segments neuropeptide Y (0.1-100 nM) did not induce any contractile response. However, if the catecholamine neuronal uptake blocker cocaine was added to the tissue bath, neuropeptide Y induced a contraction which could be fully blocked by prazosin (1000 nM). Furthermore, an age-dependent increase in the contraction to neuropeptide Y plus cocaine was observed. In conclusion, in the rat tail artery an apparent direct vasoconstrictor effect of neuropeptide Y occurs only in the presence of cocaine. Since this contraction can be fully blocked by prazosin, spontaneously released norepinephrine is an important component of the contraction. The discrepancy between in vivo and in vitro effects of neuropeptide Y may be explained in part by the presence of circulating vasoconstrictors. PMID- 7781690 TI - Minor alkaloids of tobacco release [3H]dopamine from superfused rat striatal slices. AB - In addition to S(-)-nicotine, several minor tobacco alkaloids ((+/-)-nornicotine, anabaseine, S(-)-anabasine, and S(-)-N-methylanabasine) are present in tobacco smoke. This study demonstrates that these alkaloids increase fractional 3H release in a concentration-dependent manner from rat striatal slices preloaded with [3H]dopamine, with desensitization of this response. The rank order of EC50 values was S(-)-nicotine (3.0 +/- 2.2 microM) > (+/-)-nornicotine (6.7 +/- 2.1 microM) > anabaseine (15.4 +/- 6.1 microM) = S(-)-N-methylanabasine (16.3 +/- 4.7 microM) = S(-)-anabasine (19.3 +/- 3.2 microM). The alkaloids did not modulate fractional 3H release evoked by electrical-field depolarization. Thus, minor tobacco alkaloids may contribute to the apparent neuroprotective effects of smoking in neurodegenerative diseases. PMID- 7781691 TI - Analysis of responses of allicin, a compound from garlic, in the pulmonary vascular bed of the cat and in the rat. AB - Allicin, diallyl disulfide-oxide, an active ingredient released from garlic is a systemic vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (0.1-1.0 mg) were studied in the intact-chest anesthetized cat and in the isolated lung of the rat under constant flow conditions. When baseline tone in the pulmonary vascular bed of the cat was raised with U46619 (11 alpha,9 alpha-epoxymethano-9 alpha,11 beta dideoxyprostaglandin F2 alpha), intralobar injections of allicin produced dose related decreases in pulmonary arterial pressure without changing left atrial pressure indicating that allicin had significant vasodilator activity in the pulmonary vascular bed when tone was increased experimentally. Allicin also decreased systemic arterial pressure in a dose-related manner. In terms of relative vasodilator activity in the cat, allicin was 100-fold less potent than sodium nitroprusside and many orders of magnitude less potent than isoproterenol. In the cat, vasodilator responses to allicin were unchanged by methylene blue or N omega-nitro-L-arginine methyl ester. Allicin also significantly diminished the pulmonary pressor response to ventilatory hypoxia in the isolated perfused rat lung. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the cat and the rat. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of endothelial-derived relaxing factor or the activation of soluble guanylate cyclase. PMID- 7781693 TI - Effects of adenosine receptor agonists and antagonists on physostigmine-induced yawning. AB - The effect of adenosine receptor agonists and antagonists on physostigmine induced yawning was investigated in intact or cannulated rats. Intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of physostigmine to rats induced yawning dose dependently. I.p. or i.c.v. treatment of the animals with atropine, theophylline, 5-N-ethylcarboxamidoadenosine (NECA) or N6 cyclohexyladenosine reduced the yawning induced by i.p. injection of physostigmine. I.p. administration of theophylline decreased the yawning induced by i.c.v. injection of physostigmine. The inhibitory action of N6 cyclohexyladenosine (i.p.) also was decreased by 8-phenyltheophylline (i.p.) pretreatment. It is concluded that yawning induced by a central cholinergic mechanism and a central adenosine mechanism interacts with the cholinergic induced behaviour. PMID- 7781692 TI - Selective inhibition of myosin phosphorylation and tension of hyperplastic arteries by the kinase inhibitor HA1077. AB - To examine possible alterations in myosin light chain phosphorylation in hyperplastic arteries, rabbit strips from right hyperplastic and left normal control carotid arteries were used for experiments 6 weeks after the ballooning procedure. When the hyperplastic artery was stimulated with various concentrations of K+ (10, 20, 30, 40 and 60 mM), the maximal tension in response to each concentration was significantly higher (P < 0.05) than that in the control artery. The maximal extent of myosin light chain phosphorylation induced by 60 mM K+ in the hyperplastic artery was also significantly higher than that in the control (55.1 +/- 4.1 vs. 45.1 +/- 3.2%, mean +/- S.D.). However, the [Ca2+]i response to elevated K+ in hyperplastic arteries was much the same as that in control arteries, when measured with fura-PE3. HA1077 (1-5-(isoquinolinesulfonyl) homopiperazine), a protein kinase inhibitor, was about 3-5 times more effective in inhibiting the tension and myosin light chain phosphorylation induced by 60 mM K+ in the hyperplastic artery than in the control artery. Nifedipine inhibited the tension and myosin light chain phosphorylation to the same extent in control and hyperplastic arteries. Thus, an alteration of the myosin light chain phosphorylation system, but not an alteration of Ca2+ mobilization, may be involved in the enhanced contraction of the hyperplastic artery. The enhanced phosphorylation of myosin light chain may be sensitive to HA1077. PMID- 7781694 TI - Antagonizing effect of morphine on the mobility and phagocytic activity of invertebrate immunocytes. AB - In the present study we have demonstrated that lipopolysaccharide (LPS) acts as an activator in the immunocytes of molluscs Planorbarius corneus, Mytilus edulis, and the insect Leucophaea maderae. This stimulatory effect, demonstrated by cellular conformational changes, is concentration- and time-dependent, and is antagonized by morphine. The inhibitory effect of morphine can be counteracted by naloxone. Morphine inhibitory action on immunocyte activity is also demonstrated by a decrease in the phagocytic activity. These data suggest that the downregulation of morphine is not limited to vertebrates but is also present in invertebrates. PMID- 7781695 TI - Discriminative stimulus effects of anandamide in rats. AB - Anandamide (arachidonylethanolamide), a putative endogenous ligand for the cannabinoid receptor, produces a tetrad of behavioral effects in mice characteristic of psychoactive cannabinoids including catalepsy, antinociception, hypothermia, and hypomobility. The present study examined the discriminative stimulus effects of anandamide in rats trained to discriminate delta 9 tetrahydrocannabinol or the potent cannabinoid receptor ligand CP 55,940 [(-)-cis 3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3- hydroxypropyl)cyclohexanol)] from vehicle. Intraperitoneal injections of anandamide substituted for delta 9-tetrahydrocannabinol and for CP 55,940; however, unlike substitution dose-effect curves with the training drugs, anandamide substitution occurred at a single dose (30 or 45 mg/kg) and was accompanied by severe decreases in response rates. The results of the present study suggest that, although systemic anandamide administration may have cannabimimetic effects similar to those of delta 9-tetrahydrocannabinol and CP 55,940, some differences in the behavioral effects of anandamide and other psychoactive cannabinoids also are apparent. PMID- 7781696 TI - Acute effects of irradiation on the rat brain: protection by glutamate blockade. AB - Riluzole (2-amino-6-trifluorothethoxy benzothiazole), dizocilpine (MK-801; (+)-5 methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine maleate), and lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2-triazine), agents reported to have neuroprotective actions, and WR2721 (S-2-(3-aminopropylamino) ethylphosphorothioic acid), a radioprotector, were evaluated in 15-day-old rats that underwent a 2.5 Gray (Gy) irradiation from a cobalt 60 source. 20 min after irradiation, riluzole (0.5-8 mg/kg), dizocilpine (0.1-1 mg/kg), lamotrigine (25 mg/kg), WR 2721 (75 mg/kg) or vehicle, were injected intraperitoneally. 6 h after irradiation, behavioural and histological evaluations revealed that exposure to 2.5 Gy caused hypolocomotion, stumbling gait and somnolence, which was significantly reduced, from the dose of 4 mg/kg i.p. of riluzole. A dose dependent protection of neurones in the dentate gyrus, starting from the dose of 1 mg/kg i.p. was also seen. Dizocilpine caused behavioral modifications but significantly reduced neuronal damage. Lamotrigine significantly increased neuronal damage while WR 2721 conferred no protection. In conclusion, two blockers of glutamatergic neurotransmission conferred significant protection against brain damage caused by ionizing irradiation when administered subsequent to exposure. PMID- 7781697 TI - The effect of opiates on the secretion of transmitter from amphibian motor nerve terminals. AB - The effects of dynorphin-A, dermorphine and morphine on the secretion of transmitter from the toad (Bufo marinus) motor nerve terminal have been determined. Intracellular recordings of miniature end plate potentials (m.e.p.p.s) and evoked end plate potentials (e.p.p.s) were used to estimate quantal content (m) and binomial parameters p and n. Dynorphin-A, and to a lesser extent morphine, decreased (m) while dermorphine had no significant effect on m. Dynorphin-A (ED50 = 24 microM) was 21 times more potent then morphine (ED50 = 510 microM) in decreasing m. The decrease in m produced by dynorphin-A and morphine was accompanied by a greater decrease in the variance (S2) of number of quanta secreted per stimulation over the recording period. The decrease in m produced by dynorphin-A, and to a lesser extent by morphine, is probably mediated by the opiates acting on kappa-opioid receptors. PMID- 7781698 TI - Antihyperglycemic effects of M16209, a novel aldose reductase inhibitor, in normal and diabetic rats. AB - The effect of a single oral administration of M16209 (1-(3-bromobenzo[b]furan-2 yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on serum glucose was investigated. In normal rats, M16209 (100 mg/kg) had a weak hypoglycemic effect but markedly stimulated the disappearance of serum glucose in intravenous glucose tolerance tests. In diabetic rats, M16209 (100 mg/kg) significantly suppressed the hyperglycemia of streptozotocin-induced, mildly diabetic rats and stimulated serum glucose disappearance in neonatally streptozotocin-induced, non-insulin dependent diabetes mellitus (NIDDM) rats in glucose tolerance tests. Additionally, M16209 augmented insulin secretion in glucose-loaded, normal and NIDDM rats and restored the reduced serum insulin in streptozotocin-induced, mildly diabetic rats. M16209, however, showed no hypoglycemic effect in severely diabetic rats. In contrast, gliclazide, a sulfonylurea, showed a much more potent hypoglycemic effect in normal rats than in mildly diabetic rats. These results suggest that M16209 suppresses hypoglycemia through augmentation of glucose stimulated insulin secretion. The antihyperglycemic activity of M16209, combined with its potent aldose reductase inhibiting activity, is expected to be beneficial in the treatment of diabetic complications. PMID- 7781700 TI - Novel arylaminopyridazine-GABA receptor antagonists examined electrophysiologically in Ascaris suum. AB - The structure-activity relationships of 35 novel derivatives of 2-(carboxypropyl) 3-amino-4-methyl-6-phenyl pyridazine (SR 95103) were examined as gamma aminobutyric acid (GABA) antagonists in the flap preparation of the parasitic nematode, Ascaris suum, using a two-microelectrode current-clamp technique. All but one of the potent antagonists displaced GABA dose-response curves to the right without reduction in the maximum response. The dissociation constants of the more potent competitive antagonists were described using a model which assumed that two molecules of GABA were required to open the ion channel but that only one molecule of antagonist acted on each ion channel. By exploring the structure-activity relationship, the potency of the antagonist was increased from a KB of 64 microM for SR 95103 to a KB of 4.7 microM for NCS 281-93 (2-(3 carboxypropyl)-3-amino-4-phenylpropyl-6-phenyl pyridazine). PMID- 7781699 TI - Effects of M16209 on insulin secretion in isolated, perfused pancreases of normal and diabetic rats. AB - We investigated the stimulatory effect of M16209 (1-(3-bromobenzo[b]furan-2-yl sulfonyl)hydantoin), a novel aldose reductase inhibitor, on insulin secretion using isolated, perfused pancreases of rats. In the pancreases from normal rats, M16209 (100 microM) greatly augmented glucose-stimulated insulin secretion, but showed no effect on unstimulated insulin secretion at 2.8 mM glucose. In contrast, gliclazide (10 microM), a sulfonylurea, strongly enhanced both glucose stimulated and unstimulated insulin secretion. Sorbinil and epalrestat, potent aldose reductase inhibitors, had no stimulatory effect on insulin secretion. M16209 (100 microM) improved appreciably the decreased insulin response to 22.2 mM glucose and enhanced slightly unstimulated insulin secretion in the pancreases of rats with neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM). Gliclazide (10 microM), however, failed to affect the pancreases of NIDDM rats. Furthermore, M16209 showed no appreciable effect on ATP sensitive K(+)-channels in pancreatic beta-cells. These results suggest that M16209, unlike sulfonylureas, selectively enhances glucose-stimulated insulin secretion in both normal and NIDDM rats through a direct action on the pancreas. The site of action remains unknown, but the inhibition of aldose reductase or the ATP-sensitive K+ channels is unlikely to be involved. PMID- 7781701 TI - Effect of MDL 73,745 on acetylcholine and biogenic amine levels in rat cortex. AB - We postulate that the effect of cholinesterase inhibitors to ameliorate the cholinergic deficit in Alzheimer's disease is related to their ability to maintain long-lasting, non-toxic steady-state levels of acetylcholine in cortex. We investigated the effect of the cholinesterase inhibitor, MDL 73,745 (2,2,2 trifluoro-1-(3-trimethylsilylphenyl)ethanone), on the extracellular levels of acetylcholine, norepinephrine, dopamine and 5-hydroxytryptamine in the cerebral cortex of the rat by high-performance liquid chromatography coupled with electrochemical detection. The drug significantly increased acetylcholine levels above the baseline at 2 and 10 mg/kg s.c., but not at the 1 mg/kg dose. At both 2 and 10 mg/kg there was a good correlation between cholinesterase inhibition and acetylcholine increase in cortex. At the 2 and 10 mg/kg doses, the maximal cholinesterase inhibition was 64% and 77%, respectively, and the increase in acetylcholine release was 481% and 1016%, respectively. Norepinephrine and dopamine, but not 5-hydroxytryptamine levels, were also significantly increased by the 10 mg/kg dose. The increases of norepinephrine and dopamine levels reached a maximum of 124% and 370%, respectively, and continued for a period of at least 8 h. Cholinergic side-effects were most marked at the 10 mg/kg dose but were also noticeable at the 2 mg/kg dose in the form of fasciculations, tremor and splay. PMID- 7781702 TI - Alpha 1-adrenoceptor subtype selectivity of tamsulosin: studies using livers from different species. AB - The subtype selectivity of the alpha 1-adrenoceptor antagonist, tamsulosin, was tested using hepatocytes and liver membranes from guinea pigs and rabbits (expressing alpha 1-adrenoceptors with alpha 1A pharmacology) and rats (alpha 1B adrenoceptors). Tamsulosin blocked the alpha 1-adrenergic activation of phosphorylase with higher affinity in hepatocytes from guinea pigs and rabbits than in those from rats. [3H]Tamsulosin binding to liver membranes was rapid, reversible and saturable. The Kd values obtained also indicated higher affinity for alpha 1A-adrenoceptors (70 and 140 pM, for liver membranes obtained from guinea pigs and rabbits, respectively) than for those of the alpha 1B-subtype (510 pM). Chloroethylclonidine potently and completely inactivated [3H]tamsulosin binding sites in membranes from rabbit and rat livers, but not those in guinea pig liver membranes. Binding competition and inactivation experiments were performed to further characterize the receptor subtypes present in the livers of these animals. In summary, tamsulosin is a very potent alpha 1-adrenoceptor antagonist that has higher affinity for alpha 1A-adrenoceptors than for those of the alpha 1B-subtype. PMID- 7781704 TI - Thiomuscimol, a new photoaffinity label for the GABAA receptor. AB - Thiomuscimol inhibits [3H]muscimol binding to brain GABAA receptors. Exposure of Ag(+)-treated membrane preparations to UV radiation at 254 nm for 40 min in the presence of thiomuscimol (10(-5) M) produced a 20-30% irreversible decrease in high-affinity [3H]muscimol binding sites. The photoaffinity labeling of thiomuscimol was inhibited by GABA (10(-4) M) added prior to exposure to UV light. The data show that thiomuscimol can label the GABAA receptor site and that the ligand can be used as a photoaffinity label for purification and identification of GABA binding sites within the GABAA receptor complex. PMID- 7781703 TI - The role of carbon monoxide in lucigenin-dependent chemiluminescence of rat alveolar macrophages. AB - We have investigated the role of carbon monoxide (CO) in lucigenin-dependent chemiluminescence of alveolar macrophages from rat lungs. CO (10 nM to 1 microM) decreased chemiluminescence of alveolar macrophages in a concentration-dependent fashion. At a concentration of 1 microM, CO significantly increased intracellular cyclic GMP levels from a control value of 175 +/- 25 fmol/2 x 10(6) cells to 431 +/- 49 fmol/2 x 10(6) cells. Pretreatment of alveolar macrophages with NG monomethyl-L-arginine (100 microM) failed to inhibit CO (1 microM)-induced decreases in chemiluminescence of alveolar macrophages (3.7 +/- 0.7 cpm x 10(3) in the presence of NG-monomethyl-L-arginine and 3.4 +/- 0.6 cpm x 10(3) in the absence of NG-monomethyl-L-arginine) and CO (1 microM)-induced increases in intracellular cyclic GMP levels (452 +/- 65 fmol/2 x 10(6) cells in the presence of NG-monomethyl-L-arginine and 419 +/- 58 fmol/2 x 10(6) cells in the absence of NG-monomethyl-L-arginine). Decreases in chemiluminescence of alveolar macrophages induced by CO (1 microM) were concentration-dependently inhibited by methylene blue (from 0.1 microM to 10 microM). Dibutyryl cyclic GMP (db cyclic GMP) (1 mM) also reduced chemiluminescence of alveolar macrophages (1.5 +/- 0.3 cpm x 10(3) in the presence of db cyclic GMP and 3.6 +/- 0.6 cpm x 10(3) in the absence of db cyclic GMP). In contrast to CO and db cyclic GMP, zinc protoporphyrin-9 (10nM to microM), an inhibitor of heme oxygenase potentiated chemiluminescence of alveolar macrophages in a concentration-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781705 TI - Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells. AB - Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor subtype was excluded since the selective agonist 2 methylthioATP had weak effect with lower potency than ATP. When we studied the involvement of other nucleotides similar effects were seen of the purines ATP, GTP and ITP; also the pyrimidine UTP had powerful mitogenic effects (Emax = 52% of ATP) with similar potency. Nucleotides with fewer phosphate groups showed a stepwise fall in mitogenic effect. This indicates involvement of a nucleotide receptor (P2U). Ap4A were of equal potency and effect as ATP. There was strong correlation between the mitogenic effects of the nucleotides and analogues with both 45Ca(2+)-influx and inositol phosphate (IP) production, indicating that they may participate in mediating the mitogenic response. This is the first study describing the potencies for the mitogenic effects of the selective ATP-analogues and other nucleotides in vascular smooth muscle cells. The receptor characterisation indicates a nucleotide-receptor similar to the receptor which stimulates 45Ca(2+)-influx and inositol phosphate-formation in rat aorta smooth muscle cells. Substances related to ATP such as GTP, ITP, UTP and Ap4A which also can be released extracellularly in vivo stimulate mitogenesis of rat aorta smooth muscle cells through the same receptor. PMID- 7781706 TI - Pharmacological identity between somatostatin SS-2 binding sites and SSTR-1 receptors. AB - Somatostatin (SRIF) SS-2 binding sites were originally defined in rat brain cerebral cortex membranes using [125I]Tyr11-SRIF-14 in the presence of 120 mM NaCl. These sites were characterized by their high affinity for SRIF-14 and SRIF 28, but very low affinity for cyclic peptides such as octreotide (SMS 201-995) and seglitide (MK 678). The characteristics of SS-2 sites are reminiscent of 125I]CGP 23996-labelled sites in rat brain which have been termed SRIF-2 sites. In the present study, the pharmacological profile of SS-2 sites was determined in radioligand binding studies performed in rat cortex membranes using [125I]SRIF-14 in the presence of 120 mM NaCl and compared to that of human SSTR-1 receptors expressed in human embryonic kidney (HEK 293) cells, using [125I]SRIF-14. The rank orders of affinity of a variety of SRIF analogues and synthetic peptides for SS-2 binding sites and recombinant human SSTR-1 receptors were very similar and correlated highly significantly (r = 0.99). However, SS-2 binding correlated also with binding to recombinant SSTR-4 receptors (r = 0.91). Autoradiographic studies were performed using the radioligand [125I]CGP 23996 which has been claimed to label selectively SRIF-2 binding sites and compared with the distribution of SSTR 1 receptor mRNA determined using in situ hybridization in rat brain. Although some overlap was observed between the distribution of SSTR-1 mRNA and [125I]CGP 23996 binding sites, the latter were clearly more widespread, suggesting this ligand to label SSTR-1 and other sites. In addition, inhibition of forskolin stimulated adenylate cyclase was investigated in HEK 293 cells transfected with human SSTR-1 receptors; a variety of SRIF analogues and short synthetic peptides behaved as agonists at adenylate cyclase and displayed a rank order of potency highly similar to that observed for these compounds at SS-2 binding sites. Seglitide acted as an antagonist at SSTR-1 receptor mediated inhibition of adenylate cyclase activity with a pKB of 4.42. It is concluded that the pharmacological profile of SS-2 binding sites resembles most closely that of SSTR 1 receptors (although similarities with SSTR-4 receptors were observed), that [125I]CGP 23996 labels presumably several SRIF receptors in rat brain, and that SSTR-1 receptors are negatively and efficiently coupled to adenylate cyclase activity. PMID- 7781707 TI - Characterization and distribution of somatostatin SS-1 and SRIF-1 binding sites in rat brain: identity with SSTR-2 receptors. AB - Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies performed in rat brain cerebral cortex membranes using [125I]204 090 (a radiolabelled Tyr3 analogue of SMS 201-995, octreotide). SRIF-1 recognition sites were defined in binding studies performed with [125I]MK 678 (seglitide). Both SS-1 and SRIF-1 sites were characterized by their high affinity for SRIF-14, SRIF-28 and for cyclic peptides such as octreotide and seglitide, in marked contrast to SS-2 and SRIF-2 sites which have very low affinity for these synthetic SRIF analogues. In the present study, SS-1 and SRIF-1 radioligand binding studies were performed in rat cortex membranes and compared to results obtained in cloned Chinese hamster ovary cells expressing human SSTR-2 receptors using [125I]204-090 and/or [125I]MK-678. The rank orders of affinity of a variety of SRIF analogues and synthetic peptides for SS-1/SRIF-1 binding sites and recombinant SSTR-2 receptors were very similar and correlated highly significantly (r = 0.94-0.99); by contrast, correlation between SS-1 and SSTR-5 (r = 0.44) or SSTR-3 binding (r = 0.07) was not significant. Autoradiographic studies were performed in rat brain using both radioligands [125I]204-090 and [125I]MK-678 and compared with the distribution of SSTR-2 receptor mRNA determined using in situ hybridization. A clear overlap was observed between the distribution of SSTR-2 mRNA and binding sites labelled with both radioligands. SSTR-2 receptor-mediated inhibition of forskolin-stimulated adenylate cyclase in Chinese hamster ovary cells by a variety of SRIF analogues and short synthetic peptides displayed a rank order of potency highly similar to their rank order of affinity at SS-1/SRIF-1 binding sites. It is concluded that SS-1 and SRIF-1 binding sites respectively labelled with [125I]204-090 and [125I]MK 678, both display the pharmacological profile of SSTR-2 receptors, that the distribution of [125I]204-090 and [125I]MK-678 binding sites in rat brain is superimposable and largely comparable to that of SSTR-2 mRNA expression. It is also shown that neither [125I]204-090 nor [125I]MK-678 label SSTR-3 or SSTR-5 receptors in rat brain. Finally, it is demonstrated that SSTR-2 receptors can very efficiently couple to adenylate cyclase activity in an inhibitory manner. PMID- 7781708 TI - Calcitonin gene-related peptide selectively increases cAMP levels in the guinea pig ureter. AB - Calcitonin gene-related peptide (CGRP, 0.1 microM) and forskolin (10 microM) both produced a time-dependent accumulation of cAMP in homogenates of the guinea-pig ureter, while cromakalim (3 microM) was ineffective. Neither agent did increase the cGMP levels. cAMP accumulation induced by CGRP or forskolin was unchanged by glibenclamide (1 microM). In sucrose gap, the application of forskolin (1-10 microM for 15 s) hyperpolarized the smooth muscle membrane and its effect was greatly enhanced when tested in a low-K+ medium (extracellular K+ reduced from 5.9 to 1.2 mM). The hyperpolarization produced by 10 microM forskolin was reduced and abolished by 1 and 10 microM glibenclamide, respectively, in both normal and low-K+ medium. The present findings demonstrate that CGRP determines a selective cAMP accumulation in the guinea-pig ureter and suggest that elevation of cAMP may be involved in the opening of glibenclamide-sensitive K+ channels in the ureter smooth muscle. PMID- 7781710 TI - Inhibitory effect of sevoflurane on nitric oxide release from cultured endothelial cells. AB - We investigated the effect of sevoflurane (fluoromethyl-2,2,2-trifluoro-1 (trifluoromethyl) ethylether) on intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) release from cultured porcine aortic endothelial cells using fura-2 fluorometry, and direct (ESR spectrometry with NO-trapping by 2-(4 carboxyphenyl)-4,4,5,5-tetramiethylimidazoline-1-oxyl 3-oxide) or indirect (nitrite accumulation measured by Greiss reaction) NO measurement. Sevoflurane alone did not change resting [Ca2+]i, but diminished bradykinin-induced transient increase in [Ca2+]i in a concentration-dependent manner. The inhibitory effect of sevoflurane on bradykinin-induced transient rise in [Ca2+]i was larger than that of a non-selective Ca2+ channel blocker (CO2+). Application of sevoflurane following bradykinin-evoked [Ca2+]i transient diminished [Ca2+]i significantly, while bradykinin B2 receptor antagonist (D-Arg-[Hyp3, Thi5,8, D-Phe7] bradykinin) or CO2+ abolished it. Sevoflurane impaired nitrite accumulation stimulated by bradykinin, and reduced the amount of NO released from endothelial cells. Our results indicate that the negative effect of sevoflurane appears to be due to the inhibition of bradykinin-induced Ca2+ efflux from endoplasmic stores and Ca2+ influx through membrane Ca2+ channels. PMID- 7781709 TI - LU52396, an inhibitor of the store-dependent (capacitative) Ca2+ influx. AB - The effects of 1-[2-(4-fluorophenyl)cyclohexyl]-2-[4-(3-phenylalkyl)-piperazin -1 yl]- ethanol, LU52396, on a) Ca2+ influx across the plasma membrane and b) Ca2+ mobilization from intracellular rapidly-exchanging Ca2+ stores were investigated in HeLa cells and in isolated microsomal fractions derived from the cerebellum and the skeletal muscle. LU52396 was found to be a potent inhibitor (Ki of about 2 microM) of the Ca2+ influx activated by depletion of intracellular Ca2+ stores, a phenomenon referred to as store-dependent or capacitative Ca2+ influx. Such an effect, which was reversed by cell washing, was mediated neither by a depolarization of the cell, with decrease in the driving force for cation influx, nor by a change of the intracellular pH, and might therefore be due to a direct action of the drug on either the responsible channel in the plasma membrane or, less likely, on its regulatory mechanisms. Additional effects, i.e. inhibition of receptor-mediated Ca2+ influx, of Ca2+ release from intracellular stores via either inositol 1,4,5-trisphosphate or ryanodine receptors, and of Ca2+ reuptake into the stores via sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPases, were also induced by the drug, however at concentrations 20-fold or more than those effective on the store-dependent influx. To our knowledge LU52396 is the first pharmacological tool that is found to be addressed with some preference to the store-dependent Ca2+ influx. It promises, therefore, to be useful for the characterization of the process, the identification of the responsible channel and, possibly, also of the molecular mechanisms through which these channels operate. PMID- 7781711 TI - Cyclic nucleotide phosphodiesterase isozymes in rat mesangial cells. AB - We characterized cyclic nucleotide phosphodiesterases isolated from rat mesangial cells and assessed their roles in regulating cellular cyclic nucleotide levels. Three peaks of phosphodiesterase activity were eluted by a linear sodium acetate gradient from a Q Sepharose column loaded with the mesangial cell extract. The first peak activity was stimulated by Ca(2+)-calmodulin and inhibited by calmodulin-stimulated phosphodiesterase inhibitors but not by a selective cGMP specific phosphodiesterase V inhibitor. The second, minor activity peak was stimulated by cyclic GMP and inhibited by EHNA [erythro-9-(2-hydroxy-3-nonyl) adenine], a selective inhibitor of cyclic GMP-stimulated phosphodiesterase II. The last peak activity was not inhibited by cyclic GMP but selectively inhibited by rolipram [4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidene] or Ro 20-1724 [4 (3-butoxy-4-methoxybenzyl)-2-imidazolidinone], inhibitors of cyclic AMP specific, cyclic GMP insensitive phosphodiesterase IV. Based on their order of chromatographic elution, kinetic properties and sensitivity to allosteric agents and inhibitors, the peak 1, 2 and 3 correspond to phosphodiesterase I, II and IV. The basal cyclic GMP level was raised more effectively by selective inhibitor of phosphodiesterase I than phosphodiesterase II. In contrast, the atrial natriuretic factor-induced cyclic GMP elevation was potentiated more effectively by selective inhibitors of phosphodiesterase II than phosphodiesterase I. The forskolin-induced cyclic AMP increase was greatly potentiated by selective phosphodiesterase IV inhibitors but not by other phosphodiesterase inhibitors. These data suggest that phosphodiesterase I and II are responsible for cyclic GMP hydrolysis whereas phosphodiesterase IV is mainly responsible for cyclic AMP hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781712 TI - Ca2+ handling mechanisms underlying neuropeptide Y-induced contraction in canine basilar artery. AB - The effects of neuropeptide Y on isometric tension simultaneously measured with cytosolic Ca2+ concentration ([Ca2+]cyt) and Ca2+ sensitivity of contractile elements were studied in isolated canine basilar arteries. Neuropeptide Y (1-100 nM) increased [Ca2+]cyt and tension in a concentration-dependent and parallel manner, whereas 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619) (10-100 nM), a thromboxane A2 mimetic, produced a large contraction with a small increase in [Ca2+]cyt. Ca2+ channel antagonists such as d-cis-diltiazem (10 mM) abolished both [Ca2+]cyt and tension augmented by neuropeptide Y. In Ca(2+)-free solution containing 0.2 mM EGTA, neuropeptide Y did not change [Ca2+]cyt and tension, whereas U46619 transiently increased both of them. Furthermore, neuropeptide Y apparently did not affect the Ca2+ sensitivity when assessed in the artery permeabilized with Staphylococcus aureus alpha-toxin, whereas U46619 augmented it. These findings suggest that neuropeptide Y-induced contraction in the canine basilar artery is produced mainly by Ca2+ influx through L-type Ca2+ channels. PMID- 7781713 TI - Long-term haloperidol elevates dopamine D4 receptors by 2-fold in rats. AB - Chronic treatment of rats with neuroleptics results in elevated numbers of dopamine D2-like receptors. The present study was done to determine whether neuroleptics altered the density of one type of dopamine D2-like receptors, namely the dopamine D4 receptor. We here describe the effect of a one-month treatment with haloperidol on dopamine D4 receptor mRNA and protein levels in rat striatum. Endogenous levels of dopamine D4 receptor mRNA in rat striatum are very low and, therefore, reverse transcription and subsequent amplification were used for quantification. Dopamine D4 receptor density was, because of the absence of a dopamine D4 receptor specific [3H]ligand, determined by the difference between the number of binding sites for [3H]nemonapride and [3H]raclopride. Scatchard analysis of [3H]nemonapride and [3H]raclopride binding show that treatment for one month with halperidol elevates the density of dopamine D4 receptors in rat striatum by approximately 2-fold, whereas dopamine D2 and D3 receptors together show a 19% higher receptor density. Dopamine D4 receptor mRNA was also approximately increased by 2-fold. PMID- 7781714 TI - Characterization of the human liver alpha 1-adrenoceptors: predominance of the alpha 1A subtype. AB - The alpha 1-adrenoceptor subtype present in human liver membranes was studied using radioligand binding techniques. [3H]Prazosin binding was rapid, saturable and reversible. A kinetically derived Kd of 0.22 nM was obtained. Rosenthal analysis of saturation isotherms indicated a single class of binding sites with a Kd of 0.47 nM and a Bmax of 70 fmol/mg of protein. Membrane preincubation with chloroethylclonidine markedly decreased total binding (62% decrease) without altering the Kd for the radioligand. Binding competition experiments were performed and the order of potency for agonists was: oxymetazoline > epinephrine > or = norepinephrine > methoxamine. The binding affinity for epinephrine was modulated by the GTP analogue guanosine-5'-(beta,gamma-imido)triphosphate. For antagonists the potency order was: WB4101 > or = prazosin > or = (+)-niguldipine = 5-methylurapidil > or = benoxathian > or = phentolamine. The pharmacological profile of the [3H]prazosin binding sites of human liver membranes suggests that alpha 1A-adrenoceptors predominate (75%-85% of the alpha 1-adrenoceptors) in this tissue. PMID- 7781715 TI - Endogenous [3H]flunitrazepam binding in human embryonic kidney cell line 293. AB - Specific endogenous [3H]flunitrazepam binding sites were identified and characterized in membranes from the human embryonic kidney (HEK) cell line 293. A large part of these binding sites exhibited an intermediate affinity for [3H]flunitrazepam and a microM affinity for diazepam, clonazepam, 1-(2 chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK 11195) or 4'-chlorodiazepam (Ro 5-4864). These sites, thus, resembled neither gamma aminobutyric acidA (GABAA) receptor associated nor 'peripheral' benzodiazepine binding sites. A small part of the binding sites labeled by [3H]flunitrazepam seemed to belong to 'peripheral' benzodiazepine binding sites exhibiting a nM affinity for PK 11195, and another small part of the binding sites seemed to exhibit a high affinity for flunitrazepam and PK 11195. Although small amounts of mRNA for alpha 1-, beta 3- and gamma 2-subunits of GABAA receptors could be identified in HEK 293 cells, neither the actual expression of GABAA receptors in these cells nor a coassembly of endogenous subunits with transfected GABAA receptor subunits could be demonstrated by binding studies. PMID- 7781717 TI - Dizocilpine enhances striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity. AB - Dizocilpine administration enhances dopamine metabolism in the rat striatum, nucleus accumbens, olfactory tubercle, and prefrontal cortex. Concomitant with increased metabolism is enhanced tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities in the striatum and increased mRNA for the two enzymes in the midbrain. Activation of dopaminergic neurons may, in part, explain increased locomotor activity in normal animals and the ability of dizocilpine to potentiate the antiparkinsonian action of L-3,4-dihydroxyphenylalanine in an animal model. PMID- 7781716 TI - In primary neuronal cultures muscarinic m1 and m3 receptor mRNA levels are regulated by agonists, partial agonists and antagonists. AB - The homologous regulation of the muscarinic m1 and m3 receptors mRNA was studied in rat corticostriatal neuronal cultures. In response to the full agonist carbachol the m1 and m3 receptor mRNA levels were modulated and showed different time-courses. The m1 receptor mRNA increased to 270% of prestimulation levels after 6 h, while the m3 receptor transcript transiently increased to 170% after 2 h. Conversely, the muscarinic receptor partial agonist oxotremorine caused a rapid and sustained increase in both mRNA species as soon as after 1 h of exposure. A comparable increase in both receptor mRNAs was induced by the partial agonist [4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethyl-ammonium chloride] (McN-A-343). The observation that 1 h exposure to the non selective antagonist N methyl-scopolamine also enhanced the m1 and m3 receptor transcripts suggests that in corticostriatal neurons muscarinic receptor partial agonists exert an antagonist-like effect on the m1 and m3 receptor mRNAs. PMID- 7781719 TI - Natural head position and natural head orientation: basic considerations in cephalometric analysis and research. AB - Natural head position (NHP) provides the key for meaningful cephalometric analysis because an extracranial reference line is used instead of intracranial reference lines, known to be subject to considerable biological variation in their inclination. Although the principle of natural head position is being recognized in the orthodontic literature, its registration may contain an element of unavoidable error that requires correction. A new concept of natural head orientation (NHO) has been introduced to maximize the contribution of NHP to cephalometrics. It is defined as the head orientation of the subject perceived by the clinician, based on general experience, as the natural head position in a standing, relaxed body and head posture, when the subject is looking at a distant point at eye level. The present study was designed to determine the accuracy and validity of NHO, using lateral profile photographs cut in a circular shape, obtained from 27 orthodontic patients, 10-14 years old. Findings among four investigators showed a high correlation (r = 0.82-0.96), in orientating these profile photographs in estimated natural head position (NHP). Moreover, investigators showed good correlation (r = 0.57-0.84) in head orientation after a 3-week interval. Mean differences for the same period varied between 0.1 and 2.9 degrees. The validity of NHO was supported also by a panel investigation. Clinicians as well as auxiliary personnel can be trained to make a critical judgement of the recorded natural head position and correct head orientation, whenever indicated, to enhance the reliability of cephalometric analysis in clinical practice and research. PMID- 7781720 TI - Quantitative and qualitative assessment of enamel surface following five composite removal methods after bracket debonding. AB - The search for an ideal enamel surface finishing method following bracket debonding has met with equivocal response. In this study, four other methods were assessed to determine their effectiveness against the slow speed tungsten carbide bur which is regarded as the established method of removing residual composite. Orthodontic brackets were bonded on 50 premolar teeth extracted for orthodontic purpose. After debonding with a standardized technique, the teeth were randomly divided into five equal groups. Samples in each group were subjected to different finishing procedures: Group A--Ormco band removing plier. Group B--Komet slow speed tungsten carbide bur. Group C--High speed ultrafine diamond bur. Group D- Jet high speed tungsten carbide bur. Group E--High speed white stone finishing bur. For consistency, the finishing procedures were limited to 15 seconds with each particular method. The composite remnants which then remained on the enamel surface were graded by four independent raters using the Composite Remnant Index (CRI). Subsequent to this, the enamel surface was examined in a Scanning Electron Miscroscope at x203 magnification. The photomicrographs were then graded by the same four independent raters using the Surface Roughness Index (SRI). Statistical analysis with the Friedman test indicated that there was no significant difference in inter-examiner variability in both the CRI and SRI assessment, but there existed significant difference among groups (P < 0.01) for both the CRI and SRI. It was found that no single absolute method was considered to be ideal for composite removal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781718 TI - A photographic scale to measure facial aesthetics. AB - The aim of this study was to develop a measurement scale to quantify facial aesthetics. Four series of 36 standardized facial photographs (boys 11-13 years; girls 11-13 years; boys 14-16 years; girls 14-16 years) were judged twice by eight orthodontists, eight laymen, and eight children. This was undertaken by comparing each photograph with one reference photograph of a child of the same sex and age. Pearson's correlation coefficients were calculated to determine intra-observer agreement (median Pearson's correlation r = 0.78), and to assess the correlation between the scores of each judge and those of the others in that panel (median Pearson's correlation r = 0.71). Alpha coefficients were calculated as a measure for the reliability of the composed scores (median alpha coefficient alpha = 0.90). Finally, the correlation between the three jury panels was established (median Pearson's correlation r = 0.84). The results showed that the reproducibility of rating facial aesthetics is good. Moreover, a high level of agreement was found between the ratings of different panels. Therefore, a mean overall score for each judged photograph could be calculated. Finally, for each age and sex group a metric scale was composed, consisting of five photographs with their scores. These scales can be used to evaluate the results of orthodontic treatment with respect to facial aesthetics. PMID- 7781721 TI - The effect of a lip bumper on lower dental arch dimensions and tooth positions. AB - The effect of a lip bumper on the dimensions of the lower dental arch and on the inclination of the incisors and first molars was studied in 40 children, aged 9 12 years. The children wore their lip bumper full time for 7-10 months. The effects of the lip bumper therapy were recorded on dental casts and profile cephalograms made before and after the treatment. The positions and stages of development of the lower second molars were determined on pretreatment intra-oral radiographs. The lip bumper treatment resulted in an increase of the dental arch widths between the molars, premolars, and canines. The arch length increased through proclination of the incisors and uprighting of the first molars. The stages of development and the positions of the second molars had no influence on the effect of the treatment. Simultaneous treatment in the maxilla with a headgear, a transpalatal arch or a removable plate had no influence on the outcome of the lip bumper therapy. PMID- 7781722 TI - Long-term evaluation after chincap treatment. AB - The purpose of this study was to investigate the skeletal changes occurring during and after chincap therapy. The subjects of this study, with a mean age of 9 years 3 months, consisted of 27 patients; all of whom possessed an anterior crossbite. Of these patients, 15 had skeletal Class III and the remaining 12 had skeletal Class I malocclusions with anterior crossbites. The applied total force with the chincap was 600 grams and the mean treatment period was 12 months. The changes during and after treatment were analysed by using linear and angular cephalometric measurements. The result obtained in this investigation was that in skeletal Class I and Class III cases, successfully treated by a chincap appliance, where the necessary overjet and overbite relationship was obtained, the abnormality tended to return to the original position during the period following chincap removal. PMID- 7781723 TI - An in vitro comparison between a bonded retainer system and a directly bonded flexible spiral wire retainer. AB - Bonded lingual retainers are becoming more popular to stabilize the results of orthodontic treatment. The in vitro shear strength of a flexible spiral wire (FSW) retainer (Zachrisson, 1977, 1983) bonded with Prisma Fil was compared to the 'A'-Company bonded lingual retainer system, bonded with either Concise or Right-On, to human enamel. Statistical analysis of the results showed no significant differences between the 'A'-Company system when bonded with Concise or Right On, Concise having a greater mean bond strength, but also a greater range of bond strength values. All the materials tested gave bond strengths that were adequate for clinical practice and it is concluded that the choice of bonded retainer system can be made upon grounds of clinical convenience or cost. PMID- 7781724 TI - The prediction of distortion in formed orthodontic appliances. AB - The theoretical prediction of the onset of distortion within a retraction U-loop as derived from a knowledge of the maximum bending moment, the wire characteristics and the loop dimensions was found to be in good agreement with the experimental measurements carried out on large scale models of the U-loops. The ability to predict distortion in appliances should be of use in any comparison of the properties of the different designs of U-loop or in the evaluation of different designs of orthodontic appliance. PMID- 7781725 TI - Human dental pulp and gingival tissue after static magnetic field exposure. AB - The aim of this intra-individual study was to examine human dental pulp and gingival tissue after exposure to static magnetic fields generated by orthodontic samarium-cobalt magnets. In seven individuals, aged between 11.5 and 17.5 years, the maxillary first premolars and immediately adjacent gingival tissues were exposed to a static magnetic field from a bonded magnet on one side (test) and a demagnetized magnet was used as a control on the contralateral side. After a period of 8 weeks the test and control teeth were clinically examined regarding gingival conditions, then biopsies of the buccal gingival tissues were taken and the maxillary first premolars were extracted. The teeth and the tissue biopsies were examined histologically. The static magnetic field exposure (flux density) of the coronal pulp sections on the test sides ranged between 100 and 150 Gauss, and the exposure of the buccal gingival tissues ranged between 200 and 900 Gauss. The contralateral control tissues were exposed to flux density values at the level of the natural magnetic field on earth (0.3-0.6 Gauss). Static magnetic fields produced by orally placed orthodontic rare earth magnets did not result in any change in human dental pulp or gingival tissue adjacent to the magnets. There was no difference in clinical gingival conditions between test and control sites. PMID- 7781726 TI - Prevalence and severity of apical root resorption of maxillary anterior teeth in adult orthodontic patients. AB - The purpose of this study was to evaluate prevalence and severity of apical root resorption of maxillary anterior teeth in a large sample of adult orthodontic patients, to analyse any difference between subgroups of patients with and without a history of earlier orthodontic treatment, and to test the hypothesis that endodontically treated teeth are less likely to experience apical root resorption. Differences in tooth length measurements of standardized periapical radiographs made before and after treatment of 343 adults, representing groups of consecutively treated patients from four orthodontic practices, were calculated. Sample means of averaged root resorption of all six anterior teeth and of the most severely resorbed tooth per patient were 0.94 mm (SD 0.88) and 2.39 mm (SD 1.43), respectively. Forty per cent of the adults had one or more teeth with 2.5 mm resorption or greater. The subsample of 31 patients with a history of earlier orthodontic treatment had less root resorption than the remaining patients (P < 0.001). Evaluation of the 39 contralateral pairs of teeth with and without endodontic treatment in 36 of the patients revealed less resorption of the endodontically treated teeth (P < 0.05). PMID- 7781727 TI - Epidemiology of Pseudomonas aeruginosa keratitis in contact lens wearers. AB - This study evaluated the epidemiology of Pseudomonas aeruginosa keratitis in contact lens (CL) wearers; the relationships between CL storage case contamination and CL hygiene practice and between CL hygiene and the development of keratitis. Sixteen CL wearers with keratitis were compared with 44 asymptomatic controls. Lens hygiene practice was assessed and CL care materials, domestic water sites and endogenous sites were evaluated microbiologically. Poor CL hygiene was not associated with Ps. aeruginosa keratitis. There was an association between keratitis and bacterial contamination of the CL and storage case (P < 0.0005). Lens and storage case contamination were not significantly associated with poor hygiene. No domestic or endogenous source for Ps. aeruginosa was found. Causative organisms may be derived from other sources, but CLs and CL storage cases provide a favourable environment for Ps. aeruginosa colonization. Changing the CL care environment to one less favourable for Ps. aeruginosa may help to eliminate this problem. PMID- 7781728 TI - Correlation of change in phage type with pulsed field profile and 16S rrn profile in Salmonella enteritidis phage types 4, 7 and 9a. AB - Using pulsed-field gel electrophoresis (PFGE) and 16S rRNA (rrn) analysis (ribotyping), the in vivo derivation of strains of Salmonella enteritidis PTs 9a and 7 from a strain of S. enteritidis PT 4 has been demonstrated. All strains were isolated from a single patient over a 6-week period. Further studies have demonstrated that in terms of pulsed-field profile and ribotype, the genotypes of the patient-derived strains differed from those of the reference strains of the respective phage types. It is concluded that when used in combination, these methods can provide evidence of phylogenetic relationships in apparently unrelated S. enteritidis phage types isolated during pathogenesis of disease. PMID- 7781729 TI - Epidemiology of Campylobacter spp. at two Dutch broiler farms. AB - Broiler flocks on two Dutch poultry farms were screened weekly for the presence of campylobacter in fresh caecal droppings during eight consecutive production cycles. Hatchery and fresh litter samples were taken at the start of each new cycle. Water, feed, insects, and faeces of domestic animals, present on the farms were also included in the sampling. Penner serotyping of isolates was used to identify epidemiological factors that contribute to campylobacter colonization in the broiler flocks. Generally, broiler flocks became colonized with campylobacter at about 3-4 weeks of age with isolation percentages of 100%, and stayed colonized up to slaughter. A similar pattern of serotypes was found within the various broiler houses on one farm during one production cycle. New flocks generally showed also a new pattern of serotypes. Most serotypes isolated from the laying hens, pigs, sheep and cattle were different from those isolated from the broilers at the same time. Campylobacter serotypes from darkling beetles inside the broiler houses were identical to the ones isolated from the broilers. No campylobacter was isolated from any of the hatchery, water, feed or fresh litter samples. Conclusive evidence of transmission routes was not found, but results certainly point towards horizontal transmission from the environment. Horizontal transmission from one broiler flock to the next one via a persistent contamination within the broiler house, as well as vertical transmission from breeder flocks via the hatchery to progeny, did not seem to be very likely. PMID- 7781730 TI - Restriction fragment length polymorphisms among the flagellar genes of the Lior heat-labile serogroup reference strains and field strains of Campylobacter jejuni and C. coli. AB - Several typing systems have been described for Campylobacter jejuni and C. coli, to assess the complex epidemiology of these important enteric pathogens. In the present study two typing methods, slide agglutination according to the Lior scheme, and the demonstration of restriction-fragment length polymorphisms (RFLP) of flagellar genes, have been used in parallel on a set of 194 strains. This set comprised 118 sero-reference strains of C. jejuni and C. coli of the Lior scheme, as well as 76 clinical isolates. All isolates were serotyped and subjected to PCR for amplification of flagellar genes, and the PCR product was restricted with Alu I. Flagellar genes could be amplified in 152 strains. Among 85 seroreference strains, 74 different RFLP patterns were observed, and among 67 clinical isolates, there were 36 patterns. There was only limited correlation between flagellar RFLP and the Lior serogroup, and the variability of patterns in serogroups HL2 and HL4 were as marked as the variability between serogroups. Flagellar gene RFLP patterns are shown to be stable, highly discriminatory epidemiologic markers. PMID- 7781731 TI - Sporadic isolates of Escherichia coli O157.H7 investigated by pyrolysis mass spectrometry. AB - Thirty-six encoded isolates of Escherichia coli. 32 of which were of serotype O157, were examined by pyrolysis mass spectrometry (PyMS). Thirty-one of the serotype O157 isolates possessed the flagellar antigen H7 and produced Verocytotoxin (VT), the other isolate serotyped as H45 and was non-toxigenic. Eighteen of the VT-producing E. coli (VTEC) isolates were from sporadic disease in residents of the Northern Region. Standard principal component (PC) and canonical variate (CV) analysis of the data distinguished only the four non-O157 isolates from the remainder which were indistinguishable by this approach. A similarity matrix based on differences between individual CV means distinguished a further ten isolates. The matrix correctly clustered 2 pairs of isolates from siblings and 4 isolates from an affected family. A further 5 clusters of 3 or more isolates and 6 pairs of isolates were defined. These groupings proved to be homogenous for toxin phenotype but occasionally entrained isolates of dissimilar phage type. However, in general, PyMS-derived clustering of apparently sporadic isolates accorded with geographical locations as determined by postcode. PyMS, which is a quick and high volume capacity phenotypic technique, may be a useful addition to existing methods in the investigation of the epidemiology of sporadic VTEC disease. PMID- 7781732 TI - Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source. AB - A summer outbreak of severe gastroenteritis followed by haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura in a nursery school and kindergarten is described. Sandwiches prepared with green butter made with contaminated parsley were the likely vehicle of infection. The parsley originated from an organic garden in which manure of pig origin was used instead of artificial fertilizers. Clonally identical verotoxinogenic Citrobacter freundii were found as causative agents of HUS and gastroenteritis and were also detected on the parsley. PMID- 7781733 TI - The epidemiology of Haemophilus influenzae type b disease in the Republic of Ireland. AB - A 2-year case-control study was conducted to describe the epidemiology of Haemophilus influenzae type b (Hib) and investigate Hib disease risk factors in the Republic of Ireland. Between October 1991 and September 1993. 149 laboratory confirmed incident cases were matched with community controls. Annual Hib disease incidence was 25.4 per 100,000 children under 5 years, with peak incidence (65.8 per 100,000) in the 6-11 months age-group. Meningitis was the predominant clincial condition. Twenty-four (16.1%) isolates were resistant to ampicillin. Creche or day-care attendance and the presence of chronic illness emerged as risk factors for Hib disease. Empirical first line treatment for suspected Hib infection warrants alternatives to ampicillin such as cefotaxime. Completed immunization with Hib conjugate vaccine by 6 months of age is required for maximum disease prevention. Until all children are receiving Hib vaccine on schedule, those who are creche or day-care attendees and those with chronic illness should be prioritized for timely immunization. PMID- 7781734 TI - High prevalence of antibodies to Chlamydia pneumoniae; determinants of IgG and IgA seropositivity among Jerusalem residents. AB - The prevalence of antibodies to Chlamydia pneumoniae was examined in a stratified random sample of 581 Jerusalem adult residents between August 1987 and March 1989. IgG and IgA titres were measured by microimmunofluorescence, and associations with smoking and socio-demographic variables were assessed. IgG antibodies were found in 84.5% (95% confidence interval (CI): 80.4-87.9) of men and 68.7% (95% CI: 61.6-75.0) of women (P < 0.0001 for sex difference), indicating a very high rate of exposure in this population. IgA antibodies, postulated to represent persistent infection, were present in 45.1% (95% CI: 40.1 50.2) of men and 23% (95% CI: 17.4-29.7) of women (P < 0.0001 for sex difference). Factors associated with IgG seropositivity included family size, education and social class. On the other hand age (in men) and smoking were associated with IgA seropositivity. These findings support the hypothesis that low socioeconomic status and household crowding may be predictive of exposure to or infection with this organism (IgG seropositivity), whereas they do not explain persistence of the infection putatively expressed as IgA seropositivity. PMID- 7781735 TI - Feasibility study for identifying adverse events attributable to vaccination by record linkage. AB - To investigate the feasibility of using a record linkage method for identifying vaccine attributable adverse events, computerized hospital admissions and vaccination records from South East Kent district were linked and checked for accuracy. Records for 90% of children under 2 years of age admitted to hospital over a 2-year period were matched with vaccination records using a computer algorithm based on name, date of birth, sex, and post-code supplemented by visual inspection. Relative to this gold standard, matching on date of birth, sex and postcode alone had a sensitivity of 60% and an incorrect match rate of 0.2% after matches to more than one vaccine recipient were excluded. Manual checking of a sample of admissions showed that only 4% had been assigned incorrect International Classification of Disease (ICD) codes. Routine record linkage of ICD admission codes to vaccination records therefore yields data of good quality which may be used for surveillance purposes. PMID- 7781736 TI - Isolation of epidemic poliovirus from sewage during the 1992-3 type 3 outbreak in The Netherlands. AB - To examine the extent of wild poliovirus circulation during the 1992-3 epidemic in the Netherlands caused by poliovirus type 3, 269 samples from sewage pipelines at 120 locations were examined for the presence of poliovirus. The epidemic virus strain was found in 23 samples, all from locations inside the risk area which contained communities that refuse vaccination for religious reasons. By sewage investigation, the wildtype virus was shown to be present in the early phase of the epidemic at two locations, one week before patients were reported from that area. The wild type 3 poliovirus was also detected retrospectively in a river water sample collected for other reasons three weeks before notification of the first poliomyelitis case, at a site a few kilometres upstream the home village of this patient. Oral poliovirus vaccine (OPV) virus was found at 28 locations inside or at the border of the risk area. Trivalent OPV was offered to unvaccinated or incompletely-vaccinated persons living in this region as part of the measures to control the epidemic. PMID- 7781737 TI - Sequence variation in the haemagglutinin-neuraminidase gene of human parainfluenza virus type 3 isolates in the UK. AB - The sequence variation in a 934 base-pair region of the gene encoding the haemagglutinin-neuraminidase of five human parainfluenza virus type 3 (HPIV3) isolates was determined together with that of a prototype UK strain. All of the clinical isolates were from the Manchester area of the UK and were obtained in 1990, 1991 and 1993. The gene segment was amplified by the polymerase chain reaction using HPIV3-specific oligonucleotide primers. The nucleotide homology of the strains was high, around 99% and specific differences in the UK sequences when compared with that of the US prototype strain were identified. In addition, a number of isolate-specific differences were seen. No correlation was detected between the observed nucleotide mutations and the year of isolation, which supports the hypothesis that HPIV3 shows cocirculation of a heterogeneous population of viruses rather than varying with time in a linear fashion. However, the data suggested that geographically-defined genetic lineages of HPIV3 may exist. PMID- 7781738 TI - Serosurvey and laboratory diagnosis of imported sandfly fever virus, serotype Toscana, infection in Germany. AB - Of eight acute infections in German tourists caused by sandfly fever virus, serotype Toscana (TOS), and diagnosed clinically and serologically, seven were acquired during visits to Tuscany, Italy, and one to Coimbra, Portugal. An indirect immunofluorescence assay (IFA) using infected cells, and a newly developed enzyme-immunoassay (EIA) using crude virus antigen prepared from infected Vero-E6 cells was used to detect anti-TOS IgM and IgG. In a seroepidemiological survey of 859 health care workers and medical students, anti TOS IgG was detected in 1.0% by IFA, and in 0.7% by EIA. In 2034 German patients hospitalized for various diseases, 1.6% were positive for anti-TOS IgG by IFA, and 0.8% by EIA. Anti-TOS IgG was detected in 43 samples of commercial immunoglobulins at titres of 10-1000 by EIA. Although the seroprevalence of antibodies to TOS is low in Germany, TOS infection should be considered in patients returning from endemic areas who complain of fever, and headaches, and have symptoms of meningitis. PMID- 7781739 TI - Serological studies of influenza viruses in pigs in Great Britain 1991-2. AB - Samples from a sow serum bank representative of the pig population of Great Britain collected during 1991-2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of classical swine H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9.9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza. PMID- 7781740 TI - Acetylcholinesterase in the developing ferret retina. AB - The function of acetylcholinesterase (AChE) is to terminate the action of acetylcholine at the cholinergic synapse. Recent evidence suggests additional roles for acetylcholinesterase as a peptidase and/or a protease which is expressed by growing neurites as part of their invasion of developing neural structures. We report the localization of acetylcholinesterase in developing ferret retina. AChE histochemical staining is seen in the developing inner plexiform layer (IPL) of ferret retina at birth (post-natal day zero, PO), the earliest developmental stage examined. Transient expression is seen at the border between the ganglion cell layer and the nerve fiber layer at P14 and P21. A small amount of transient expression is seen in the outer plexiform layer (OPL) at this age as well. By P28, the transient expression in the OPL is at its peak, and is found at photoreceptor terminals and associated with apparent horizontal cell axons. Labeling is also seen intracellularly in the inner nuclear layer (INL), at the OPL/INL border, suggesting that horizontal cells are the source of the transient AChE expression in the OPL. Overt synaptic profiles also appear in the inner plexiform layer (IPL) at P21 and P28. About 2 days layer, the eyes open and the photoreceptor outer segments are fully developed. By 2 weeks later, at P42, the AChE staining pattern in the retina has taken on its adult appearance: no reaction product in the outer retina; intracellular reaction product in the Golgi apparatus of a subset of amacrine and displaced amacrine cells which manufacture AChE; and extracellular reaction product at both synaptic and non-synaptic sites in the IPL. These data are consistent with a role for AChE as a peptidase early in development, and as an enzyme essential in the termination of synaptic action at mature synapses. PMID- 7781741 TI - Structure and composition of the rodent lamina cribrosa. AB - To define the architecture and extracellular matrix composition of the lamina cribrosa in rodents, normal, adult pigmented rat and guinea pig eyes were frozen and sectioned for light microscopic immunohistochemistry. Antibodies specific for collagens I, III, IV and VI, laminin, elastin, and chondroitin and dermatan sulfate proteoglycans were exposed to longitudinal and cross-sections of optic nerve heads and their binding distributions observed with the avidin-biotin peroxidase complex technique. Cross-sections of the intraocular portion of the rat optic nerve head revealed a horizontally oval shape with distinct, vertically oriented, laminar beams. The guinea pig optic nervehead cross-section was circular, with randomly oriented beams. In both animals, collagens I, III and VI were found throughout the laminar beams, along with elastin fibrils. Collagen IV and laminin antibodies deposited along laminar beam margins and within the beams, representing astrocytic and vascular endothelial cell basement membranes. Both animals showed evidence for dermatan and chondroitin sulfate-containing proteoglycans in all connective tissue structures of the nerve head. In the rat, chondroitin-4 sulfate proteoglycans appeared localized to the sclera and laminar beams. The rat and the guinea pig optic nerve head possess an identifiable lamina cribrosa with structural proteins nearly identical to that of the primate. Both animals may provide affordable alternative animal models for in vivo studies on the role of the lamina cribrosa in glaucomatous optic nerve damage. PMID- 7781742 TI - Immunocytochemical study of cytochrome P450 (1A1/1A2) induction in murine ocular tissues. AB - C57BL/6 and DBA/2 mice were injected intraperitoneally with beta-naphthoflavone in corn oil and killed 48 hr later. Control animals received an injection of corn oil. The immunoreactivity of cytochrome P450 1A1/1A2 expressed in different ocular tissues and liver was examined with goat anti-P450 antibody (primary antibody) and gold-conjugated anti-goat antibody (secondary antibody). DBA/2 mice, which are non-responsive to aryl hydrocarbon treatment, showed negligible levels of immunoreactivity toward anti-P450 1A1/1A2 antibody in all ocular tissues, whether or not the animals were treated with beta-naphthoflavone. In responsive C57BL/6 mice, however, the immunoreactivity of the uveal tissues, especially ciliary non-pigmented epithelium, was markedly increased by beta naphthoflavone treatment. The time course of induction of P450 1A1/1A2 immunoreactivity was very similar for the liver and ciliary non-pigmented epithelium, although the maximum level of immunoreactivity of the ciliary epithelium reached in 48 hr after inducer treatment was about 25% of that of liver. The present results support our previous observations that the P4501A enzyme activities (e.g. aryl hydrocarbon hydroxylase) in the liver and eye of C57BL/6 mice are under the same genetic regulation. Further, this study is the first demonstration of P450 isoform induction in specific ocular tissues of the whole animal. PMID- 7781743 TI - Calcium cataract: a model for optical anisotropy fluctuations. AB - Young rat lenses were incubated in organ culture media enriched with 20 mM calcium. Lenses in the calcium rich medium developed cataracts and were characterized by the absence of vimentin in the urea soluble protein fractions. Sections from the same lenses were studied by polarized light scattering. The I+/Iparallel scattering intensity ratios were higher from the lenses in calcium rich media than from the control lenses. This indicated an increase in the optical anisotropy fluctuations during cataractogenesis. The turbidity that developed due to these fluctuations was caused partly by the disappearance of vimentin and which in turn caused the enhancement of birefringence of the lens. PMID- 7781744 TI - Frequency of glutathione-S-transferase 1 gene deletion and its possible correlation with cataract formation. AB - This experiment was conducted to investigate the possible association between an increased frequency of glutathione-S-transferase (GST)1 gene deletion and the presence of cataracts in elderly patients. Genomic DNA was isolated from blood samples obtained from 138 elderly patients who had undergone cataract surgery, and from 62 random blood donors. All subjects lived in the same geographic area (Ibaraki Prefecture, Japan). The DNA sequences among three different exon ranges (exons 3-5, exons 4-5 and exons 5-6) of the GST1 gene were amplified by the polymerase chain reaction (PCR) technique to determine if GST1 gene deletion occurred. Cataract patients had a significantly higher frequency of GST1 gene deletion than random controls did (P < 0.001, odds ratio = 2.91, 1.56-5.44; 95% of confidence interval). Mean age of cataract patients lacking GST1 gene was significantly younger (n = 101, mean age = 70.4, s.d. = 10.2) than that of patients possessing the GST1 gene (n = 37, mean age = 75.0, s.d. = 8.7) (P < 0.02). These results show that the deletion of the GST1 gene may be one of determinants of genetic susceptibility to cataractgenic agents. PMID- 7781745 TI - Inflammation induced changes in adenosine 3',5'-cyclic monophosphate production by ciliary epithelial cell bilayers. AB - Despite extensive evidence implicating the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha) in the intraocular inflammatory response, little is known about their effects on signal transduction in anterior uveal tissue. Since these cytokines have been shown to alter the adenylyl cyclase system in nonocular tissues, we tested the hypothesis that IL-1 beta and TNF alpha affect the anterior uvea by altering production of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) in ciliary epithelial bilayers. This was accomplished by measuring the levels of cAMP in bilayers ex vivo, following intraocular inflammation induced by intravitreal injection of IL 1 beta, TNF alpha or bacterial endotoxin, and in vitro, following exposure to IL 1 beta, TNF alpha or bacterial endotoxin. Although cAMP production was enhanced in bilayers from IL-1 beta-, TNF alpha- or endotoxin-inflamed eyes, ex vivo, exposure of normal bilayers to IL-1 beta (15 U ml-1), TNF alpha (20 U ml-1), or a low concentration of endotoxin (0.01 microgram ml-1) for 4 hr, in vitro, had no effect on cAMP production. The inability of IL-1 beta, TNF alpha, or the low concentration of endotoxin to increase cAMP production by bilayers, in vitro, suggests that the enhanced cAMP production observed with inflamed bilayers, ex vivo, was not due to a direct action of these inflammatory agonists on the ciliary epithelial bilayer. Although direct exposure to cytokines or endotoxin did not change cAMP production, treatment with IL-1 beta, TNF alpha, or a higher concentration of endotoxin (1 microgram ml-1) did affect signal transduction mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781746 TI - The late positive retinal potential in dogs. AB - The late positive potential of the mammalian electroretinogram has been called the 'PI' or the 'c-wave' potential. It is unusual among retinal potentials because its peak implicit time increases in response to increasing stimulus intensity and because it cannot be demonstrated consistently in small samples of normal humans or normal dogs. We recorded wideband (DC-1 kHz) responses from 34 normal Beagles or dogs of similar size. Of the 34, 11 produced a late positive potential set that satisfied the criteria for c-waves. Multiple aspartate injections always increased c-wave amplitude and stimulus-response linearity in all 'producers'. Non-producers were never converted to producer status by aspartate blocking of the inner retina. Interaction of late positive and negative potentials and the possible influence of normal individual variations in the trans-epithelial potential are discussed. Individual mammal c-wave production is controlled by outer retinal phenomena which vary between individuals. PMID- 7781747 TI - In vitro studies on the assembly properties of the lens proteins CP49, CP115: coassembly with alpha-crystallin but not with vimentin. AB - A rapid one-step purification procedure for CP49, an intermediate filament protein found in the lens, is described using reverse-phase HPLC. This protein is one of the major intermediate filament proteins of the lens fibre cells and is found in both the water insoluble fraction (WIF) and the water soluble fraction (WSF) of the lens. In order to better understand the physiological role of CP49 in lens transparency we have purified CP49 from both compartments and compared the in vitro assembly characteristics of both by electron microscopy and sedimentation assays. Our studies showed that CP49, when mixed with another lens intermediate filament protein, CP115, forms 10 nm intermediate filaments. Vimentin, another intermediate filament protein found in the lens, was unable to coassemble with CP115, thus demonstrating the specificity of the interaction of CP49 with CP115. CP49 isolated from either the WIF or the WSF formed 10-nm filaments with CP115 and indicated that CP49 from both these lens cell compartments had similar in vitro assembly characteristics. This also suggested that the post-translational modifications observed for CP49 from the different compartments was of little apparent consequence to filament formation. The inability to reconstitute beaded filaments from CP49 and CP115 suggested that other lens proteins may be needed in the reconstitution assay before these lens specific cytoskeletal elements could be repolymerised from their purified protein components. CP49 and CP115 were therefore assembled in the presence of alpha crystallins and a beaded filament structure was observed as has been seen with type III intermediate filament proteins assembled with alpha-crystallins. PMID- 7781748 TI - Characterization of neutral glycosphingolipids in rat lens. AB - Neutral glycosphingolipids were purified from non-cataractous lenses of Sprague Dawley rats by a combination of solvent extraction, Folch's partition, and column chromatography using DEAE-Sephadex and Iatrobeads. Six major GSLs from monohexosylceramide to pentahexosylceramide were identified by sugar composition analysis, methylation analysis and glycosidase digestion. Structural relationships among the six neutral glycosphingolipids revealed metabolic pathways leading to the synthesis of Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1 ceramide (IV3Gal alpha nLc4), instead of a Lewis(x) glycolipid (Gal beta 1- 4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1 ceramide, III3FucnLc4), from neolactotetraosylceramide (nLc4), together with isoglobotriaosylceramide (iGb3). The alpha-galactosyl epitope, Gal alpha 1-3Gal R, is evolutionarily conserved in many types of cells of non-primate mammals, prosimians and New World monkeys, but not in those of Old World monkeys or humans. This evolution-related difference in carbohydrate epitopes suggests different cell-to-cell attachments, which may be mediated through cell surface glycosphingolipids, between rat and human lenses. PMID- 7781749 TI - Tumour necrosis factor-induced uveitis in the Lewis rat is associated with intraocular interleukin 6 production. AB - Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 microgram). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of intraocular interleukin 6 production were determined. At 24 hr after intravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared to saline-treated controls (P < 0.05). Maximal clinical uveitis and blood-aqueous barrier breakdown were already present at 4 hr after tumour necrosis factor injection. The uveitis was characterized by a massive cellular infiltrate in the anterior segment, consisting predominantly of polymorphonuclear cells and macrophages/monocytes, and to a lesser extent of T lymphocytes. Intraocular interleukin 6 mRNA expression and elevated levels of interleukin 6 in aqueous humor were detected 1 hr after tumor necrosis factor injection, reached a maximum at 3 to 4 hr after injection, and had declined again at 2 hr. Although intracardial injection of 1 microgram of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The results obtained with intravitreally injected tumour necrosis factor indicate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleukin 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necrosis factor. PMID- 7781751 TI - A study of phase separation in eye lens homogenate by means of speckle techniques. PMID- 7781750 TI - Evidence of retinoid metabolism within cells of inner retina. PMID- 7781752 TI - Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy. AB - Peripheral blood progenitor cells (PBPCs) were collected without prior association with chemotherapy but after the administration of granulocyte macrophage colony-stimulating factor (GM-CSF) produced in Chinese hamster ovary cells (CHO-GM, regramostim), Escherichia coli (E. coli-GM, molgramostim), or yeast (Yeast-GM, sargramostim) and used in conjunction with autologous bone marrow after high-dose chemotherapy in 69 patients with breast cancer or melanoma. The mean peripheral white blood cell (WBC) counts increased by 2.2 to 2.7-fold after regramostim, 4.5 to 7.3-fold after molgramostim and 4.3-fold after sargramostim. All patients underwent three leukaphereses. The mean (+/- standard error) total nucleated pheresed cells per kg x 10(8) were 4.15 +/- 0.56, 15.10 +/ 1.77 and 7.24 +/- 1.00 for patients receiving regramostim, molgramostim or sargramostim respectively. The mean (+/- standard error) granulocyte-macrophage colony-forming units per kg x 10(4) mobilized into the PB were 8.75 +/- 3.63, 71.03 +/- 17.85, and 65.11 +/- 18.74 for patients receiving regramostim, molgramostim, or sargramostim respectively. The total mean (+/- standard error) CD34+ cells per kg x 10(7) collected by three leukaphereses were 3.28 +/- 1.62, 1.34 +/- 0.51 and 2.57 +/- 1.93, for patients receiving regramostim, molgramostim or sargramostim respectively. The use of either molgramostim- or sargramostim primed PBPCs led to complete elimination of absolute leukopenia with a WBC count under 100/mm3 in 64% and 77% of patients treated, respectively. Patients receiving molgramostim-primed PBPCs required fewer red blood cells transfusions than patients receiving regramostim-primed PBPCs (p = 0.0062). Our data indicate that PBPCs collected without prior association with chemotherapy but after either molgramostim or sargramostim with autologous bone marrow support and GM-CSF shorten the hematopoietic recovery after myeloablative chemotherapy in patients with breast cancer or melanoma. PMID- 7781753 TI - Three monoclonal IgG components, an IgG4(lambda), an IgG2(kappa) and an IgG1/IgG3 (kappa) Gm(f,b) hybrid, in a single myeloma patient. AB - An unusual triclonal IgG combination in the serum of a 56-year old male with clinical stage IIIB multiple myeloma is reported. The patient initially had an IgG4(lambda) monoclonal protein in his serum and later developed an IgG2(kappa) and an IgG (kappa) which possessed the characteristics of both IgG1 and IgG3 subclasses with an unusual combination of allotypic markers. Three M-proteins did not share idiotypic determinants. A rare class-switch recombination followed by mutation has been considered as a possible mechanism leading to this combination. PMID- 7781754 TI - Computerised method for recording platelet density distribution. AB - In the present study a computerized apparatus was employed for scanning light transmission variations along test tubes containing density-separated platelets. The device consists of a stepping motor, a stationary halogen lamp and a photopotentiometer connected to a personal computer. Anticoagulated whole blood was layered on a performed continuous Percoll gradient having a density span from 1090 kg/l (bottom) to 1040 kg/l (top). After centrifugation at 3400g for 1.5 hours, high-density cells (i.e. erythrocytes) pass through to the bottom of the test tube and the lighter platelets remain in the gradient. The test tube is moved by the computer between the halogen lamp and the photopotentiometer. Transmission variations along the gradient were recorded and registered in the computer. Density markers beads were used as an internal standard and platelet peak density was determined. After perforating the test tube the gradient was divided into 45 aliquots. In all fractions determination of platelet counts and mean platelet volume was carried out. In addition, in the aliquots having a platelet count > 20 x 10(12)/l the ratio beta-thromboglobulin per platelet was also determined. The platelet distribution in the gradient was illustrated graphically. A good agreement was found when comparing platelet distributions in the gradients and light transmission variations along the test tubes. PMID- 7781755 TI - Inversions of the factor VIII gene in Swedish patients with severe haemophilia A. AB - The series comprised 49 Swedish patients with severe haemophilia A [belonging to 49 families (21 with known and 28 with sporadic haemophilia)], of whom 12 had developed F. VIII inhibitors. Using Southern blotting, 45% (22/49) were found to have inversions, i.e., intrachromosomal rearrangements of the tip of the X chromosome. Twenty patients had one or the other of the two variants of inversions recently published, whereas 2 patients manifested novel band patterns. Inversions were found in 50% of the families with sporadic haemophilia, and in 38% of those with known haemophilia. Fourteen families with sporadic haemophilia A had inversions, the proband carrying the de novo mutation in 4 cases and the proband's mother in 10 cases. Six inversions derived from a male and five from a female X-chromosome meiosis, the origin of the remaining three was not established. Genetic counselling of patients with severe haemophilia A and their families will be considerably improved, as inversions occur in half the severe cases and can be detected by a simple Southern blotting procedure. PMID- 7781756 TI - Simultaneous measurements of megakaryocyte-associated IgG (MAIgG) and platelet associated IgG (PAIgG) in chronic idiopathic thrombocytopenic purpura. AB - We have simultaneously measured platelet-associated IgG (PAIgG) and megakaryocyte associated IgG (MAIgG) in 30 untreated patients with chronic idiopathic thrombocytopenic purpura (CITP). Megakaryocytes were purified from bone marrow by 35% Percoll gradient centrifugation, followed by negative immunopanning using magnetic immunobeads. The normal range of MAIgG in 30 healthy donors was 15.5 +/- 10.0 ng/10(5) megakaryocytes, whereas MAIgG in the 30 CITP patients was 140 +/- 59.3 ng/10(5) megakaryocytes, although the values were widely distributed. From the PAIgG and MAIgG data, CITP patients were classified into three types; type I (PAIgG < 200 ng/10(7) platelets and MAIgG < 150 ng/10(5) megakaryocytes), type II (PAIgG > 200 ng and MAIgG > 150 ng), and type III (PAIgG < 200 ng and MAIgG > 150 ng). Patients with types I and III had good clinical courses, but, in contrast, patients with type II responded poorly to steroid therapy followed by splenectomy or became refractory to treatment. In splenectomized patients, MAIgG of responder was promptly decreased to normal range and, in contrast, that of non-responder was persistently elevated. These results indicate that anti-platelet autoantibodies are able to bind with megakaryocytes in the bone marrow as well as with platelets in the peripheral blood, and the results also suggest that megakaryopoiesis in CITP is heterogeneous. Simultaneous measurement of PAIgG and MAIgG may predict the clinical outcome of CIPT. PMID- 7781757 TI - Correlation between soluble transferrin receptor and serum ferritin levels following bone marrow transplantation for thalassemia. AB - This study analyzes the serum transferrin receptor (sTfR) levels in a series of 230 ex-thalassemics with a follow-up of 1 to 9 years after bone marrow transplantation (BMT) for homozygous beta thalassemia. Ex-thalassemics are individuals, cured of homozygous beta thalassemia by BMT, who maintain different degrees of iron overload acquired during the pretransplant period. Both in experimental and clinical conditions, sTfR concentrations have been shown to be a quantitative measure of body iron status. This study was carried out to assess whether the level of sTfR may be of help in determining the extent of iron overload in ex-thalassemics. Patients who received the marrow from their HLA identical sibling donor heterozygous for beta thalassemia, namely heterozygous ex thalassemics, displayed significantly higher levels of sTfR than patients transplanted from their normal sibling donors (normal ex-thalassemics). This finding suggests that increased erythropoiesis, albeit in part ineffective in heterozygous ex-thalassemics, is responsible for the sTfR increment. Both heterozygous and normal ex-thalassemics had significant lower sTfR levels than their heterozygous (p < 0.003) or normal (p < 0.0001) donors, respectively. These differences may be ascribed to the presence of iron overload in ex-thalassemics in comparison to their normal or heterozygous donors who did not present excess of iron in the body. A significant inverse correlation between sTfR and serum ferritin levels (r = -0.54, p < 0.0001) was found when normal ex-thalassemics were considered. In heterozygous ex-thalassemics, the lack of correlation between these two parameters may be explained by the enhanced erythropoietic activity of individuals with thalassemic trait. These results suggest that the level of sTfR may be a useful indicator of iron overload in normal ex-thalassemics. PMID- 7781758 TI - Fludarabine and plasma cell leukemia. PMID- 7781759 TI - Multilobated lymphoma presenting as primary spleen lymphoma. PMID- 7781760 TI - Effect of a negative regulatory element (NRE) on the human CYP1A1 gene expression in breast carcinoma MCF-7 and hepatoma HepG2 cells. AB - The expression of the cytochrome P4501A1 gene, CYP1A1, is induced by e.g. 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) mainly by transcriptional mechanisms. The inducers mediate their effect upon binding and activation of the aryl hydrocarbon receptor (AHR) transcription-factor complex. Utilizing chimeric CYP1A1/CAT constructs transient gene expression experiments indicate that the putative negative regulatory element (NRE) of CYP1A1 influence the relative TCDD induced CAT activity in HepG2 cells, whereas this effect was not observed in MCF-7 cells. Differences in the formation of cell-specific protein-DNA complexes were demonstrated by gel retardation assays suggesting a functional difference of NRE in these two cell lines. PMID- 7781761 TI - Genomic structure of the mouse A-type lamin gene locus encoding somatic and germ cell-specific lamins. AB - Mouse A-type lamin genes were isolated. Structural analyses revealed that all the three known mouse A-type lamins (A, C and C2) were coded in a single genomic locus in a 22 kilobase DNA segment. The three lamins were coded in 12, 10 and 10 exons for A, C and C2, respectively, and shared 8 exons among them. Primer extension analyses identified possible transcription start sites for both A/C and C2 genes suggesting that the locus is under the control of two separate promoters, that is a somatic cell-acting promoter (for A and C) and a testis specific promoter (for C2) which resides in the first intron of the A/C gene. Sequence characteristics of the possible promoter regions are discussed. Divergence of the two somatic cell-type lamins (A and C) is formally accounted for by differential selection of poly(A) sites together with lamin A-specific splicing. PMID- 7781762 TI - Almost the entire 5' non-translated region of hepatitis C virus is required for cap-independent translation. AB - To investigate which hairpin structures within the 5' untranslated region of hepatitis C virus (HCV) are necessary for cap-independent translation, mutants were constructed that lack one or more hairpin structures. Here we demonstrate, by constructing precisely defined hairpin deletion mutants, that with the exception of the most 5' located hairpin structure, which on deletion shows an increase on translation, each of the predicted hairpins is found to be essential for cap-independent translation. In addition, we demonstrate that HCV 5'UTR driven translation is stimulated by poliovirus 2Apro co-expression. PMID- 7781763 TI - Amyloid beta protein (25-35) stimulation of phospholipases A, C and D activities of LA-N-2 cells. AB - [3H]Myristic acid prelabeled LA-N-2 cells were exposed to varying concentrations of amyloid beta protein (25-35), from 20 to 250 micrograms/ml, and the activation of phospholipases A and D estimated. A progressive increase in phosphatidylethanol formation, a measure of phospholipase D activity, and of free fatty acid release, a measure of phospholipase A activity, was observed over a time-course of 60 min. [3H]Inositol prelabeled LA-N-2 cells were exposed to varying concentrations of A beta P, from 20 to 125 micrograms/ml, and phospholipase C activation was measured. There was an increased release of inositol phosphates in the presence of amyloid beta protein as a function of incubation time. The effects of adrenergic, metabotropic amino acid and bombesin antagonists on the A beta P mediated stimulation of phospholipase C activity was investigated. Propranolol, a beta adrenergic antagonist, 7-chloro-kynurenic acid, a metabotropic amino acid antagonist, and [Tyr4-D-Phe12]bombesin, a bombesin antagonist, blunted the A beta P stimulation of phospholipase C activity in [3H]inositol prelabeled LA-N-2 cells. This suggests that amyloid beta protein activation of phospholipase C may be receptor mediated. The phospholipase C inhibitor U 71322 prevented the activation of phospholipase C by A beta P. However, this activation was not effected by tocopherol, propylgallate, or vitamin C. PMID- 7781764 TI - Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF like motif gamma 2III4. AB - High affinity nidogen binding of laminin-1 (chain composition alpha 1 beta 1 gamma 1) has been previously mapped to a single EGF-like motif gamma 1III4 of its gamma 1 chain. Two more isoforms, laminin-5 (alpha 3 beta 3 gamma 2) and laminin 7 (alpha 3 beta 2 gamma 1), show low and high binding activity, respectively, indicating that the gamma 2 chain is of low affinity. This was confirmed by recombinant production of the homologous EGF-like motif gamma 2III4 of the gamma 2 chain, which has a 100,000-fold lower binding activity than gamma 1III4. The crucial heptapeptide binding sequence Asn-Ile-Asp-Pro-Asn-Ala-Val of gamma 1III4 is modified in gamma 2III4 by replacing both the central Asn and Val by Ser. Changing these replacements to Asn and Val by site-directed mutagenesis enhanced the activity of gamma 2III4 to a level which was only 5-fold lower than that of gamma 1III4. Despite their high sequence identity (77%) motifs gamma 1III4 and gamma 2III4 were also shown to differ considerably in immunological epitopes. This indicates distinctly different functions for laminins which differ in the gamma chain isoform. PMID- 7781765 TI - Temperature dependent chaperone-like activity of alpha-crystallin. AB - Alpha-crystallin, a multimeric protein present in the eye lens, is known to have chaperone-like activity in preventing the aggregation of enzymes and other crystallins. We have studied the chaperone-like activity of this protein towards the aggregation of insulin B chain, induced by reducing the interchain disulphide bond with dithiothreitol. At room temperature, there is no detectable protection (at a 1:1 (w/w) ratio of insulin: alpha-crystallin) against the aggregation of insulin B chain by alpha-crystallin, whereas it completely prevents this aggregation at 40 degrees C. We have monitored the temperature dependence of the protection of aggregation by alpha-crystallin; the protection increases sharply above 30 degrees C and reaches almost 100% by 41 degrees C. Probing the hydrophobic surfaces of alpha-crystallin with the hydrophobic fluorphore 8 anilino-1 naphthalene sulfonate suggests that the hydrophobic surfaces of alpha crystallin are exposed to a greater extent above 30 degrees C. A complete prevention of the aggregation is achieved at 27.6 degrees C by increasing the concentration of alpha-crystallin by more than 8 fold. Similar temperature dependent chaperone-like activity of alpha-crystallin is observed towards the aggregation of zeta-crystallin, an enzyme crystallin from guinea pig. We have earlier shown that alpha-crystallin exposes hydrophobic surface(s) at temperatures above 30 degrees C. These results support our earlier hypothesis [Raman, B. and Rao, Ch.M. (1994) J. Biol. Chem. 269, 27264-27268] that the chaperone-like activity of alpha-crystallin is more pronounced in its structurally perturbed state. PMID- 7781766 TI - Effects of protein kinase modulators on transferrin receptor expression in human leukaemic HL-60 cells. AB - The mRNA of transferrin receptor (TfR) is constitutively expressed in proliferating human leukaemic HL-60 cells. Treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, or dibutyryl cyclic AMP (dbcAMP), a protein kinase A (PKA) activator, resulted in a 90% decrease in the level of TfR mRNA. Inhibition of TfR mRNA expression induced by 10 nM PMA and 100 microM dbcAMP was abolished by prior incubation of cells with 0.1-1.0 microM GF109203X, a PKC-specific inhibitor, and 1-10 microM H-89, a PKA specific inhibitor, respectively. The blocking effects of GF109203X and H-89 were dose-dependent and complete at the highest concentrations of the inhibitors used. Although treatment of cells with GF109203X or H-89 alone did not alter the constitutive expression of TfR mRNA, incubation of cells with 30-100 nM staurosporine, a wide-spectrum protein kinase inhibitor, resulted in suppression of the constitutive expression of TfR mRNA in a dose-dependent manner. These results suggest that (i) the down-regulation of TfR mRNA expression during the differentiation of HL-60 cells can be mediated by activation of either PKC or PKA; (ii) the constitutive expression of TfR mRNA in proliferating HL-60 cells is staurosporine-sensitive and is probably maintained by protein kinase(s) other than PKC and PKA. PMID- 7781767 TI - Preferential inhibition of phorbol ester-induced hydrolysis of phosphatidylethanolamine by N-acetylsphingosine in NIH 3T3 fibroblasts. AB - It has been reported that in rat fibroblasts cell-permeable ceramide analogs inhibit agonist-induced phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine (PtdCho). Here we demonstrate that relatively short (30 min) treatments of NIH 3T3 fibroblasts with 15-60 microM concentrations of N acetylsphingosine result in preferential, although not exclusive, inhibition of phorbol 12-myristate 13-acetate-induced PLD-mediated hydrolysis of phosphatidylethanolamine (PtdEtn). The results suggest that in different cell types the PtdEtn- and PtdCho-hydrolyzing PLD activities are differentially sensitive to the inhibitory effect of ceramide. PMID- 7781768 TI - A novel 27/16 kDa form of subtilisin cleaved actin: structural and functional consequences of cleavage between Ser234 and Ser235. AB - A new 27/16 kDa form of cleaved actin was prepared by subtilisin cleavage between Ser234 and Ser235 of F(MgADP)-actin complexed with BeFx. The cleavage had little effect on actin-actin interactions as probed in polymerization measurements and by electron microscopy. In circular dichroism melting experiments the thermostability of F-actin was reduced by about 10 degrees C by this cleavage. The in vitro motility and Vmax, but not Km, of actomyosin ATPase were decreased by about 20% upon 27/16 kDa cleavage of F-actin. The binding of tropomyosin to actin was unchanged by this modification. PMID- 7781769 TI - Nucleotide sequence encoding the di-haem cytochrome c551 peroxidase from Pseudomonas aeruginosa. AB - The nucleotide sequence of the gene encoding cytochrome c551 peroxidase from Pseudomonas aeruginosa is reported. The translated amino acid sequence differs from the sequence reported earlier by peptide mapping most significantly by the presence of a section containing an additional 20 residues. A number of minor differences are also evident. The new sequence translates to a protein containing 346 amino acids, the first 23 being typical of a hydrophobic leader peptide with a characteristic protease cleavage site. PMID- 7781770 TI - Mutational analysis of a putative polyphosphoinositide binding site in phospholipase C-beta 2. AB - The phosphatidylinositol 4,5-bisphosphate (PtdIns-P2)-regulated actin-binding protein gelsolin and most phosphoinositide-specific phospholipases C (PLCs) comprise a basic amino acid motif ((K/R)xxxKxK(K/R); x denotes any amino acid) which was previously suggested to represent a PtdInsP2-binding site commonly present in these proteins. We have challenged this hypothesis for PLC beta 2 by replacing one or several residues of this motif (KILIKNKK; residues 457-464) and examining the functional consequences of these alterations. The results show that the integrity of the basic motif is important for PtdInsP2 hydrolysis by PLC beta 2. Replacement of lysines 463 or 461 by arginine led to reduction or complete loss, respectively, of enzyme activity. The results provide further support to the concept that the function of the basic motif within the various PLCs is to bind the enzyme substrate PtdInsP2. PMID- 7781771 TI - Ecotin is a potent inhibitor of the contact system proteases factor XIIa and plasma kallikrein. AB - Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as a potent reversible tight-binding inhibitor of the human contact activation proteases factor XIIa (FXIIa) and plasma kallikrein, having Ki values of 89 pM and 163 pM, respectively. Ecotin also inhibited human leukocyte elastase (HLE) with high affinity (Ki = 55 pM). The association rate constants kon for FXIIa and kallikrein were 5.3 x 10(5) M-1.s-1 and 2.9 x 10(5) M 1.s-1, respectively. The dissociation rate constant koff for kallikrein, measured in the presence of HLE to prevent reassociation, was 6.3 x 10(-5) s-1; the koff for ecotin with FXIIa was 4.7 x 10(-5) s-1. Both FXIIa and kallikrein cleaved ecotin slowly at pH 5.0, identifying Met-84 as the P1 residue. The potent anticoagulant effect by ecotin is explained by the coincident inhibition of FXIIa, kallikrein, and FXa and suggests that it may be useful in the study of inflammatory or thrombotic disorders such as sepsis or cardiopulmonary bypass. PMID- 7781772 TI - Total antioxidant activity of low density lipoproteins and the relationship with alpha-tocopherol status. AB - A rapid method is described for measuring the antioxidant activity of low density lipoproteins. Studies were undertaken on individuals attending a hyperlipidaemia clinic, an unsupplemented group and a group after supplementation with 300 mg dl alpha-tocopherol acetate for nine weeks. The results show a positive correlation between the antioxidant activity and alpha-tocopherol content of LDL in the supplemented group. PMID- 7781773 TI - Calponin reduces shortening velocity in skinned taenia coli smooth muscle fibres. AB - Calponin (4.1-5.9 microM, pig stomach) inhibited maximal shortening velocity (Vmax) by 20-25% with only minor influence on force in skinned smooth muscle from guinea-pig taenia coli activated at different Ca2+ levels and with thiophosphorylation. Similar results were obtained with a fragment of the N terminal 1-228 amino acids engineered using a mouse cDNA construct (5.4 microM). Both the native calponin and the fragment inhibited actin filament sliding in a graded manner in an in vitro motility assay. We conclude that calponin influences the kinetics of the actin-myosin interaction in the organised smooth muscle contractile system and that engineered fragments of calponin can be used to probe its action in muscle fibres. The effects can be due to an introduction of an internal load during filament sliding, possibly by decreasing the detachment rates and increasing the cross-bridge time spent in the attached state. PMID- 7781774 TI - 1H and 13C NMR assignment and secondary structure of Chlorobium limicola f. thiosulfatophilum ferrocytochrome c555. AB - The 1H resonances of the ferrocytochrome c555 from the anaerobic green sulfur bacterium Chlorobium limicola f thio-sulfatophilum (strain Tassajara) have been assigned. Identification of spin systems and sequential assignment of 1H was accomplished by automated assignment computer programs followed by manual verification. In addition, 13C resonances have been extensively assigned by HSQC experiments at natural abundance. As determined by short-range NOE connectivities, 13C alpha chemical shifts, and HN exchange experiments, the secondary structure consists of 3 helices ranging from residues 3-13, 43-53 and 70-86. Interestingly, the second helix is significantly longer than observed by X ray crystallography [1977, Proc. Natl. Acad. Sci. USA 74, 5244-5247]. A topological model of the cytochrome c555 is presented based on a small number of long-range NOE contacts. The helices are shown to pack onto the heme according to the pattern common to all class I cytochromes c. PMID- 7781775 TI - Boar spermadhesin PSP-II: location of posttranslational modifications, heterodimer formation with PSP-I glycoforms and effect of dimerization on the ligand-binding capabilities of the subunits. AB - Spermadhesin PSP-II was isolated from the non-heparin-binding fraction of boar seminal plasma; its disulphide bridge pattern, and the location of a single N glycosylation site were established. PSP-II forms a heterodimer with specific N glycoforms of PSP-I. Although both subunits possess heparin-binding capability, the PSP-I/PSP-II complex does not. The heterodimer contains binding sites for zona pellucida glycoproteins and soybean trypsin inhibitor located in the PSP-II subunit. However, the PSP-I/PSP-II heterodimer binds only loosely to the sperm surface and is easily removed during in vitro capacitation, suggesting that the zona pellucida binding activity may not be relevant for gamete interaction. Our results show that dimerization of spermadhesins PSP-I and PSP-II markedly affects their binding capabilities. PMID- 7781777 TI - Deletion mutagenesis of heparin cofactor II: defining the minimum size of a thrombin inhibiting serpin. AB - Heparin cofactor II (HCII) is a 66 kDa plasma glycoprotein that belongs to the serpin superfamily of protease inhibitors. Its natural target is thrombin. HCII inhibits thrombin in both a progressive reaction, and in an accelerated reaction catalyzed by a glycosaminoglycan, dermatan sulphate (DS). Both modes of inhibition result in the formation of a stable, denaturation-resistant complex. Using a cDNA clone encoding rabbit HCII recently isolated and characterized in our laboratory, we have employed deletion mutagenesis to identify amino-terminal regions of the molecular which are essential to the progressive reaction. PCR was employed to produce four deletion constructs: delta 58, delta 81, delta 106, and delta 169, all in an in vitro transcription vector plasmid background. Transcription of the full-length construct, and of the four deletion constructs, followed by in vitro translation in rabbit reticulocyte lysate, was used to produce the corresponding HCII-related polypeptides. The delta 106 and delta 169 mutants failed to react with thrombin, even in the presence of DS. In contrast, the delta 58 and delta 82 mutants retained the ability to form complexes with thrombin, although the rate of complex formation was decreased for the latter mutant compared to the full-length recombinant HCII; no acceleration of complex formation in the presence of 20 micrograms/ml DS was noted for either truncated recombinant HCII. Alignment of the rabbit HCII primary structure with secondary structural elements found in alpha 1 antitrypsin and other serpins showed that the non-functional delta 106 mutant lacks helix A, while the functional delta 82 mutant contains this element. Our results suggest that helix A is an essential part of a functional serpin, and define the limits of the amino-terminal region of HCII which is not essential for thrombin inhibition. PMID- 7781776 TI - Primary structure and expression of a novel human laminin alpha 4 chain. AB - The complete primary structure of a novel human laminin alpha 4 chain was derived from cDNA clones. The translation product contains a 24-residue signal peptide preceding the mature alpha 4 chain of 1792 residues. The domain structure is similar to that of the recently described alpha 3 chain [Ryan, Tizard, Van Devanter and Carter (1994) J. Biol. Chem. 269, 22779-22787]. Northern analysis of RNA from human fetal and adult tissues revealed developmental regulation of expression. In adult, strong expression was observed in heart as well as lung, ovary, small and large intestines, placenta and liver, whereas weak or no expression was detected in skeletal muscle, kidney, pancreas, testis, prostate or brain. In contrast, fetal lung and kidney revealed high expression. In situ hybridization analysis of human fetal and newborn tissues showed expression of the laminin in alpha 4 chain in certain mesenchymal cells in tissues such as smooth muscle and dermis. PMID- 7781778 TI - The tetracycline efflux protein encoded by the tet(K) gene from Staphylococcus aureus is a metal-tetracycline/H+ antiporter. AB - The tet(K) gene from Staphylococcus aureus was highly expressed in Escherichia coli by an alteration of its initiation codon from TTG to ATG and its ribosome binding sequence from GAGG to GGAGG [Noguchi, N. et al. (1994) Biol. Pharm. Bull. 17, 352-355]. The inverted membrane vesicles prepared from the tet(K)-expressing cells showed respiration-dependent [3H]tetracycline transport comparable to the vesicles from the tet(B)-expressing cells. The affinity of Tet(K) vesicles to tetracycline was the same as that of Tet(B) vesicles, whereas the former Vmax value was about 60% of the latter one. Contrary to Tet(B) vesicles, Tet(K) vesicles showed no significant minocycline uptake, which was consistent with the low minocycline resistance of the Tet(K)-producing cells. The tetracycline transport mediated by Tet(K) vesicles was coupled with proton transport and the translocation of 60Co2+ ions as well as in Tet(B) vesicles. This observation indicates that the class K tetracycline resistance determinant from Gram-positive bacteria also encodes a metal-tetracycline/H+ antiporter that is functionally similar to that encoded by tet(B), although there is a considerable difference in the primary sequences and the putative topologies of these Tet proteins. PMID- 7781780 TI - Identification and structural characterization of a mannose-6-phosphate containing oligomannosidic N-glycan from human erythropoietin secreted by recombinant BHK-21 cells. AB - A sialidase resistant mono-charged N-glycan was isolated from glycosylation site I (Asn-24) of recombinant human erythropoietin expressed from baby hamster kidney (BHK-21) cells and constituted approximately 2-4% of the oligosaccharide material at this glycosylation site. Mass spectrometry and both 1- and 2-dimensional NMR techniques revealed a high mannose type structure (Man6) with a phospho diesterbridged N-acetylglucosamine as follows: [formula: see text] PMID- 7781779 TI - PTF1 encodes an essential protein in Saccharomyces cerevisiae, which shows strong homology with a new putative family of PPIases. AB - Complementation of a temperature sensitive mutant of the yeast Saccharomyces cerevisiae resulted in the isolation of PTF1 (processing/termination factor 1), an essential gene encoding a putative 3'-end processing or transcription termination factor of pre-mRNAs. Ptf1p shows significant homology to a newly discovered family of PPIases. This family is characterized by its insensitivity to immunosuppressive drugs and the lack of homology with cyclophilins and FK-506 binding proteins [Rahfeld et al. (1994) FEBS Lett. 352, 180-184]. Should Ptf1p display PPIase activity, it would be the first characterized, eukaryotic member of this putative family, which is essential for growth. PMID- 7781781 TI - Relevance of histidine-84 in the elongation factor Tu GTPase activity and in poly(Phe) synthesis: its substitution by glutamine and alanine. AB - Substitution of His-84 (-->Gln and -->Ala), a residue of the switch II region of E. coli elongation factor (EF) Tu, hardly affected the binding of GTP or GDP. The activity in poly(Phe) synthesis and GTP hydrolysis of EF-Tu H84Q were both reduced to about 35%, as compared to EF-Tu wt, whereas EF-Tu H84A was inactive in poly(Phe) synthesis but still showed a 10% residual GTPase activity. Phe-tRNAPhe exerted a similar inhibitory effect on the GTPase activity of EF-Tu wt and EF-Tu H84Q while abolishing that of EF-Tu H84A. Ribosomes enhanced the GTPase activity of EF-Tu H84Q, but not that of EF-Tu H84A, on which they even seemed to exert an inhibitory effect. The one-round GTP hydrolysis associated with the EF-TuH84Q dependent binding of Phe-tRNAPhe to poly(U)-programmed ribosomes was less efficient than with EF-Tu wt. Kirromycin stimulated the GTPase activities of both mutants less than EF-Tu wt. The results of this work do not support a catalytic role of His-84 in the intrinsic GTPase of EF-Tu, but they emphasize the importance of its side-chain for polypeptide synthesis and GTP hydrolysis. PMID- 7781783 TI - Glucose responsiveness of a reporter gene transduced into hepatocytic cells using a retroviral vector. AB - An MMLV-based retroviral vector containing the chloramphenicol acetyl transferase reporter gene under the control of a glucose-dependent internal promoter derived from the L-type pyruvate kinase gene was constructed. After transfection into psi CRIP packaging cells, clones producing recombinant retrovirus were selected. These retroviruses were used to infect cultured established hepatocytic cells whose endogenous L-type pyruvate kinase gene is transcriptionally regulated by glucose. In the infected cells, the reporter gene was as responsive to glucose as the endogenous L-type pyruvate kinase gene, and the glucose gene activation was time- and concentration-dependent. The possibility to confer a glucose responsiveness on a transgene carried by a retroviral vector provides a powerful tool in the prospect of gene therapy for diabetes mellitus. PMID- 7781782 TI - Human thrombin variable region 1, including E39, is involved in interactions with alpha 1-antitrypsin M358R and protein C. AB - We used an antithrombin autoantibody (IgG D), the epitope of which encompasses ABE1 and amino acids located within variable region 1, to study thrombin interactions with R358 alpha 1-AT and protein C. IgG D inhibited the thrombin interaction with R358 alpha 1-AT, while hirugen had no effect, indicating that the interaction of R358 alpha 1-AT with thrombin may involve the VR1 subsite. We also obtained evidence that VR1 may be involved in the activation of protein C by thrombin in the absence of thrombomodulin. Moreover, IgG D attenuated the inhibitory effect of calcium ions during protein C activation by thrombin, probably by masking E39 within the VR1 site. PMID- 7781784 TI - Structure-activity study of a laminin alpha 1 chain active peptide segment Ile Lys-Val-Ala-Val (IKVAV). AB - The IKVAV sequence, one of the most potent active sites of laminin-1, has been shown to promote cell adhesion, neurite outgrowth, and tumor growth. Here we have determined the structural requirements of the IKVAV sequence for cell attachment and neurite outgrowth using various 12-mer synthetic peptide analogs. All-L- and all-D-IKVAV peptides showed cell attachment and neurite outgrowth activities. In contrast, all-L- and all-D-reverse-sequence peptides were not active. Some of the analogs, in which the lysine and isoleucine residues of the IKVAV peptide were substituted with different amino acids, promoted cell attachment, but none of the analog peptides showed neurite outgrowth activity comparable to that of the IKVAV peptide. These results suggest that the lysine and isoleucine residues are critical for the biological functions of the IKVAV peptide. PMID- 7781785 TI - Breast cancer--trials on conservative surgery. PMID- 7781786 TI - Open randomized trials in the management of primary breast cancer. PMID- 7781787 TI - Breast cancer: questions for future trials. PMID- 7781788 TI - Linkage analysis and the susceptibility gene (BRCA-1) in familial breast cancer. PMID- 7781790 TI - Lymph node metastases in gastric cancer invading the submucosal layer. AB - We investigated the incidence of lymph node metastasis in 80 patients with early gastric cancer invading the submucosal layer and the relation of metastasis to other clinicopathological variables. All patients underwent curative gastric resection with lymphadenectomy. Lymph node metastasis was detected histologically in 15 patients. The incidence of nodal involvement showed significant increase paralleling the depth of cancer invasion. There was no relation between nodal involvement and histological differentiation. No patients died of gastric cancer during the follow-up. We conclude that gastrectomy with R2 lymphadenectomy is an appropriate operative method for early gastric cancer in which precise diagnosis of cancer invasion cannot be confirmed preoperatively. PMID- 7781789 TI - Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese. AB - We studied p53 overexpression in a series of 99 primary oesophageal squamous cell carcinomas (28 well-differentiated, 42 moderately-differentiated and 29 poorly differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. The p53 protein was detected in 30% (30 cases) of the tumours. A significantly higher positive rate was noted in the poorly-differentiated tumours (11% for the well differentiated, 31% for the moderately-differentiated and 48% for the poorly differentiated tumours). In addition, strong positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases and the expression was weaker in the better differentiated foci. The central keratinizing areas and the immediately adjacent tumour cells were always negative for p53. The adjacent normal oesophageal mucosa was all negative for p53 protein but the non-invasive dysplastic epithelium next to the tumours could also be strongly positive for p53 protein (four out of 14 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). In two out of these four cases, the dysplastic epithelium showed staining for p53; even the adjacent invasive tumour was negative for p53. It is concluded that there is a strong relationship between p53 overexpression and tumour cell differentiation in oesophageal squamous carcinoma and overexpression of p53 can occur in non-invasive tumour cells. PMID- 7781791 TI - Oncogenes in cancer of the pancreas. AB - A three-step immunoperoxidase staining technique was used in order to estimate the immunohistochemical expression of K-ras, c-fos, c-myc and c-erbB-2 oncoproteins, in paraffin sections of 20 patients, with histologically proven adenocarcinoma of the pancreas. The two oncogenes that were found to be associated with pancreatic adenocarcinoma were K-ras and c-erbB-2. in 15 patients (75%) and four patients (20%), respectively. Positive immunostaining was intense, cytoplasmic and was noted in a great percentage of cancer cells. The same model of expression was observed in the examined cases of metastatic tissue from liver and lymph node metastases. The expression of myc and fos oncogenes was nuclear, weak and was observed in a small number of patients. PMID- 7781793 TI - Is an immunological faecal occult blood test better than Haemoccult? A cost benefit study. AB - Immunological faecal occult blood (FOB) tests have theoretical advantages over their guaiac counterparts in that they are specific for human haemoglobin. HemeSelect is a semi-quantitative immunological FOB text. Faecal material is eluted into test diluent and serial dilutions are performed. The manufacturers recommend that erythrocyte agglutination at 1:8 dilution is considered a positive reaction. However, further serial dilutions can be carried out and the highest dilution at which the test remains positive determined. At 1:8 dilution, the test has been shown to be more sensitive for symptomatic colorectal cancer than Haemoccult. The aim of this study is to compare the positive rates, neoplastic yield and costs of Haemoccult with HemeSelect at various dilutions in asymptomatic average risk subjects aged 50-74. 1489 subjects satisfactorily completed both tests, 145 (9.7%) returned positive Hemeselect tests (read at 1:8 dilution, 38 patients with neoplasms > or = 1 cm) and 17 positive Haemoccult tests (1.1%). All positive Hemeselect tests were further serially diluted. As the Hemeselect dilution increased to 1:16, 1:32, 1:64 and 1:128 so the positive rate and yields of neoplasms > or = 1 cm progressively fell to 6.8% & 35, 3.6% & 20, 2.7% & 18 and 1.5% & 12, compared with 1.1% and eight neoplasms > or = 1 cm for Haemoccult. In spite of the unit cost of the Hemeselect test being greater than Haemoccult, the cost per neoplasm > or = 1 cm was lower for Hemeselect at 1:8 and 1:16 dilutions than Haemoccult. However, for an equivalent neoplastic yield, Haemoccult was cheaper. Hemeselect is a versatile test whose positive rate can be tailored according to the risk of the group being screened. PMID- 7781792 TI - Effect of essential fatty acids on natural cytotoxicity in patients with colorectal cancer. AB - Essential fatty acids (EFAs), have been shown to modulate lymphocyte reactivity and destroy various tumour cells in vitro. Natural cytotoxicity, mediated by NK and LAK cells, is believed to play an important anti-cancer role in vivo. The effect of EFAs, given orally as dietary supplementation, on NK and LAK cell cytotoxic activity in patients with localized (n = 10) and advanced (n = 20) colorectal cancer has been studied, using in-vitro 51Cr release cytotoxicity assays with K562 (NK) and DAUDI (LAK) cells. The activity of effector cells was expressed as lytic units. NK cell activity showed no significant change following 15 days ingestion of EFAs in the group with localized cancer, but was significantly reduced in the group with advanced disease and continued to decline, reaching minimal levels following 6 months supplementation (P = 0.017). LAK cell activity showed no overall alteration after 15 days ingestion of EFAs in patients with localized cancer, but in the group with advanced disease, the reduction in the activity occurred at day 15 and steadily declined on prolonged intake, reaching significant minimal levels after 6 months of supplementation (P = 0.05). Cell surface marker analysis (FACS-CD MABs) revealed reduced absolute numbers of CD16+, CD56+ and CD57+ lymphocytes (P < 0.05) in the patients with advanced colorectal cancer. More importantly, the cytotoxicity of NK and LAK cells returned to the pre-supplementation values, 3 months after cessation of EFA intake. Furthermore, there was no alteration in the cytotoxic activity of NK and LAK cells in the control group (advanced colorectal cancer without EFA supplementation) during the 6 months period of evaluation. These results suggest that prolonged EFA supplementation, in the doses used in this study, may have detrimental effects on natural anti-cancer cytotoxic mechanisms in patients with malignant disease. PMID- 7781794 TI - Middle and lower third rectum carcinoma: sphincter saving or abdominoperineal resection? AB - Sphincter saving resections (SSR) are performed with increasing frequency in carcinoma of the lower and middle third of the rectum. In this retrospective study local and distant recurrence and survival were compared to abdominoperineal resection (APR). In 71 women and 71 men (mean age: 64 years) with a primary adenocarcinoma between 5 and 10 cm from the anal verge 89 SSR, and 53 APR, were performed (Dukes stages--SSR--A 19%; B 30.3%; C 50.7% vs APR--A 15%; B 45.3%; C 39.6%). Patients have been followed up for a minimum of 24 months (mean time 62 months). There were no differences in intraluminal diameters of the tumours in each operative procedure. The distal tumour-free distance was more than 6 cm in 52% after APR (SSR: 10%) and less than 3 cm in 43% after SSR. Survival was not different between procedures in Dukes stages A and B. A survival advantage for patients with Dukes C carcinoma after APR did not reach statistical significance. No differences in distant spread were found for SSR (Dukes stage A 0%; B 7%; C 18%) and APR (Dukes stage A 0%; B 8%; C 14%) for local recurrence in Dukes stages A and B after SSR (A and B 0%) and APR (A 0%; B 8%) whereas a significant increase in local recurrence rate was seen in Dukes stage C after SSR (24% vs, APR 5%). Although a further resection could be performed in almost all of these patients a negative effect of local recurrence on survival occurred (25.4 months with and 80 months without local recurrence). While SSR seems to be favourable in Dukes stages A and B, APR should be considered in carcinoma of the lower and middle third of the rectum with lymphatic spread. Effective preoperative staging determines selection of the appropriate operation. PMID- 7781795 TI - Expression of epidermal growth factor receptor messenger RNA in human colorectal carcinomas assessed by non-radioactive in-situ hybridization. AB - No consensus as to the involvement of the epidermal growth factor receptor (EGF R) in colorectal carcinomas has yet been attained, although they are assumed to play a role in the metastasis to lymph nodes and recurrence of breast carcinoma and bladder carcinoma invasion. Knowing that Dukes' classification of colorectal carcinoma is closely related to prognosis, we examined whether there is a correlation between Dukes' classification and the expression of EGF-R in colorectal carcinoma. If there is a positive correlation, the involvement of EGF R in the processes may be assumed and the expression of EGF-R may be used as a marker of their prognosis. To this end, the expression of EGF-R mRNA and protein by non-radioactive in-situ hybridization and immunohistochemistry, respectively, were determined on histological preparations of formalin-fixed paraffin-embedded colorectal surgical specimens. In 30 cases of colorectal carcinoma examined, mRNA and/or protein was detected in 33% (two of six) of Dukes' A, in 40% (four of 10) of Dukes' B, in 36% (four of 11) of Dukes' C, in 33% (one of three) of Dukes' D and in 0% of normal colon epithelial cells. Thus, there was no positive correlation between the Dukes' classification and the expression of EGF-R. It is concluded that the expression of EGF-R in colorectal carcinoma is not a promising marker of prognosis. However, the role of EGF-R in EGF-R positive tumours remains to be examined. PMID- 7781796 TI - Potential value of biliary CEA assay in early detection of colorectal adenocarcinoma liver metastases. AB - Elevation of the biliary CEA level in patients with liver metastases from colorectal carcinoma has been reported. The aim of this study is to determine the potential value of biliary CEA assay in the early detection of liver metastases. Biliary and serum CEA levels were determined in patients operated on for a colorectal cancer and in control groups. Among 13 patients with liver metastases from colorectal carcinomas, biliary CEA levels were markedly elevated (> 40 ng/ml) in nine, moderately elevated (5-40 ng/ml) in two and normal (arbitrarily defined as < 5 ng/ml) in two. Of 28 patients with primary colorectal carcinoma without detectable hepatic secondaries, three had marked CEA elevation in the bile, 10 had moderate CEA elevation and 15 had normal levels. Among nine patients with non-malignant hepatobiliary pathology, there was one marked biliary CEA elevation, one moderate elevation and seven normal levels. None of the 13 individuals with no identified hepatobiliary pathology had elevated biliary CEA levels. The follow-up of patients with a primary colorectal tumour, no evidence of hepatic secondaries and a biliary CEA elevation is of particular interest. If subsequent appearance of liver metastases is found in such cases, intra-operative biliary CEA assay could be considered a valuable diagnostic test. Further studies will then have to prove the possible benefit of a specific treatment for this group of patients. PMID- 7781797 TI - Positron emission tomography: 2-deoxy-2-[18F]-fluoro-D-glucose uptake in locally advanced breast cancers. AB - Fifteen patients with locally advanced breast cancers were studied using the radiopharmaceutical 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) with positron emission tomography (PET). Five patients were sequentially imaged before and after two pulses of chemotherapy. In 14 of 15 tumours increased uptake of FDG was observed which correlated with the clinical site of the tumour. The PET images were compared with the mammographic and ultrasonomammographic appearances of the tumours in selected patients. In two patients with normal mammograms PET imaging detected the tumour and in a further four patients, with suspicious but not conclusively malignant mammographic changes, a well-defined area of increased FDG uptake was demonstrated by PET. In all five sequentially imaged tumours, following chemotherapy, there was a decrease of the FDG tumour: normal breast uptake ratio. In four patients who completed a full chemotherapeutic course this change preceded a pathological response of their tumours. These findings suggest that this technique may be of benefit in imaging carcinomas in the breasts of pre menopausal women which may appear dense on mammography and moreover, that sequential imaging may have a role in the prediction, at an early stage, of the response of locally advanced carcinomas to chemotherapy. PMID- 7781799 TI - Report of a symposium on diagnosis and treatment of adult soft tissue sarcomas in the head and neck. AB - A series of presentations and discussions was held during a symposium on the diagnosis and treatment of adult soft tissue sarcomas in the head and neck (HNSTS). The purpose of this meeting was to define guidelines on diagnosis and treatment of HNSTS. The results of this symposium are summarized and condensed in this report. Recommendations are made for diagnostic strategies and for treatment. Diagnostic efforts in PET scanning and dynamic MRI need to be expanded to detect early recurrences. Firm pathological diagnosis remains the basis for further treatment strategy. Wide surgical excision, if feasible, in combination with radiotherapy is the treatment of choice. PMID- 7781798 TI - The importance of the non-palpable lesion in women under 50, detected by mammography on self-referral for screening, symptoms or follow up. AB - Between 1.1.88 and 31.12.91, 349 consecutive patients had an x-ray localization excision of a non-palpable breast lesion less than 10 mm in diameter detected by 2-view mammography performed as a result of self-referral for screening (133), breast symptoms (164), or follow-up for breast disease (52). All lesions greater than 11 mm were excluded. 250 had benign and 99 (28%) had malignant lesions. 37 of 99 (37%) patients with malignancy were aged 49 or under. 133 patients requested screening, 33 (25%) had carcinoma of whom 11 (33%) were aged 49 or less. 164 patients presented with breast symptoms; 47 (29%) had cancer and 15 (32%) of these were aged 49 or less. 52 patients requested follow up for breast diseases including previous cancers, 19 (37%) had carcinoma of which 11 were 49 years or less (58%). 223 had microcalcifications, of which 68 (31%) were positive for cancer, and 126 had no microcalcification, of which 31 (25%) patients had cancer. The specific spiculate radiological lesions yielded 16 carcinomas in 31 cases (52%). Microcalcification was seen in 110 patients under 49 with 27 (25%) carcinomas detected. Microcalcification was a significant diagnostic criterion in the patients aged 49 or less, accounting for 27/37 (73%) patients. Dutal carcinoma in situ accounted for 18/37 (49%) in patients aged 49 or less, and 19/62 (31%) in patients over 50 years. Mammography should not be withheld from patients who are seeking screening, have symptoms, or who wish to be followed up, irrespective of age. PMID- 7781800 TI - The prevalence of different human papillomavirus types and p53 mutations in laryngeal carcinomas: is there a reciprocal relationship? AB - This study investigates whether a reciprocal association occurs between HPV infection and somatic mutation of the tumour suppressor gene p53 in laryngeal carcinomas. Using immunohistochemical techniques, 87 tumours were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. The prevalence of different HPV types in these tumours was determined by using the polymerase chain reaction and restriction enzyme analysis. Over expression of p53 was noted in 50/87 (57.5%) of the tumours investigated but not in any of the non-neoplastic laryngeal mucosa (controls). There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of laryngeal carcinomas. HPV DNA was detected in 8/36 (22.2%) of the tumours: HPV-6 in three, HPV-11 in one, HPV-16 in two, and unknown HPV type in two. In p53-mutant tumours, HPV was present in 4/20 tumours but none of these were high risk HPV types. In p53-normal tumours, on the other hand, HPV was present in 4/16 tumours but two of these were definitely high risk HPV-16. These results imply the reciprocal association between HPV and somatic mutations of p53 found in the case of cervical carcinoma. PMID- 7781801 TI - Neuroendocrine tumours in various organ systems in a ten-year period. AB - Neuroendocrine cells are present in various organ systems. These widely distributed cells as well as their histogenetically related tumours can produce various peptides and peptide hormones. From 1984 to 1993, 349 neuroendocrine tumours were found among 511,382 histological diagnoses at the Institute of Pathology of the Medical School of the Karl Franzens University in Graz. In 30% carcinoid of the appendix was diagnosed, in 16% carcinoid of the colorectum, in 9% carcinoid of the small intestine and in 2% duodenal carcinoid. Carcinoid of the stomach was detected in 14%. Seven of these cases showed microcarcinoidosis and five of them were combined with an adenocarcinoma. Carcinoid of the oesophagus was present in 1%, neuroendocrine pancreatic tumours in 6%. Neuroendocrine tumours of the bronchial system were found in 12%, medullary thyroid cancer in 5%. In 1% a Merkel-cell tumour was diagnosed. Other more rare localizations of neuroendocrine tumours were the uterus, ovary, breast, testes, epididymis, anal region and the upper respiratory tract. PMID- 7781802 TI - Is bladder conservation feasible? An Indian experience. AB - With the introduction of chemotherapy in the treatment of muscle invasive bladder cancers, endeavors at improving disease-free survival/overall survival are ongoing. As high objective response rates were seen with MVAC/CMV regimens (M methotrexate, V-vinblastine, A-adriamycin, C-cisplatin) organ conservation is being attempted. A phase II protocol was designed using MVAC as the initial therapy. Based on the response to two cycles all patients were evaluated and where possible the bladder was preserved. Twenty-nine patients completed the protocol and had a median follow-up of 24 months. Complete response (CR) was noted in 7/29 (24.1%) of patients, while 11/29 (38%) had partial response (PR) and 11/29 (38%) showed no response (NR). Bladder conservation was possible in 15/29 (51.7%) patients initially with the use of radiation therapy after the initial chemotherapy. Ten of these patients are presently alive with their bladders intact. Three patients died of distant disease, two with normal bladders and one with local relapse. Two of the other patients required salvage cystectomy and are alive and disease-free. All complete responders 7/7 (100%) and 5/11 (45%) partial responders could have their bladders conserved. Three of 11 partial responders who refused radiotherapy and 11/11 non-responders underwent radical cystectomy after initial chemotherapy. Subset analysis indicates that low stage and grade tumours had the highest likelihood of bladder preservation, and there was no difference in overall survival in the groups according to response criteria. As our study consists of a small number of selected patients, it would be improper to draw firm conclusions. However, it seems that initial chemotherapy selects out a subset of patients with a good prognosis and the chance for bladder conservation. PMID- 7781804 TI - Update on urology--prostate cancer. 1--The molecular basis for prostatic cancer: how it may influence treatment choice. PMID- 7781803 TI - Membrane ruffling of cancer cells: a parameter of tumour cell motility and invasion. AB - Membrane ruffling of cells is a dynamic and rapid movement with irregular fluctuation of protrusion and withdrawal of the margin of the cell surface membrane. The ruffling can be seen in two major types: ruffling around the periphery and leading edge of an adherent cell and circular ruffling on the dorsal surface. A number of cytokines have been shown to increase membrane ruffling, and methods of decreasing ruffling are now being reported. Membrane ruffling has been shown to relate to metastatic status in tumour cells obtained by fine needle aspiration, while in-vitro and animal tumour studies show it to be an indicator of tumour cell motility and metastatic potential. If these latter findings can be confirmed as applicable to clinical tumours as well, the establishment of such a relationship may be useful in predicting invasion and metastasis in human tumours, as well as providing a model to study methods of inhibiting or reversing metastatic potential. PMID- 7781805 TI - Paediatric surgical oncology. 4--The management of soft tissue sarcomas in children. PMID- 7781806 TI - Combined therapeutic approach for extraorbital sebaceous carcinoma in a Torre's syndrome. AB - Extraocular sebaceous carcinomas are extremely uncommon neoplasms. More exceptional is their association with an internal malignancy as first described separately by Torre and Muir in 1967. We report the first use of combined adjuvant radio- and chemotherapy in a sebaceous carcinoma of the anal margin in a Torre's syndrome. An interesting partial response was attained before the patient died from general debility. The therapeutic approach is discussed. PMID- 7781807 TI - Haemangiopericytoma of the greater omentum. AB - A case of haemangiopericytoma of the greater omentum is reported here. We discuss the presentation, treatment and prognosis of these rare tumours. PMID- 7781808 TI - Change of flow cytometric DNA content in para-aortic lymph node showing recurrence after adjuvant chemotherapy for gastric cancer. AB - A para-aortic lymph node showing recurrence was resected from a patient who had received adjuvant chemotherapy after curative resection of an advanced gastric cancer. A flow cytometric analysis of DNA content was carried out for the primary lesion, a metastatic lymph node and the resected lymph node. A peri-diploid cell population in addition to diploid cells appeared in the recurrent lesion, whereas a major diploid cell population and a minor aneuploid cell population were found in the primary lesion and the metastatic lymph node, indicating that a clone of chemo-resistant tumor cells selectively multiplied after the cytotoxic therapy. The characters of a recurrent lesion may be changed by clonal selection following chemotherapy. PMID- 7781809 TI - Insulinoma: pitfalls in preoperative localization. AB - In patients with biochemical evidence of insulinoma, many techniques have been advocated as the procedures of choice for diagnostic localization without a clear cut consensus as to their utility. Despite the small size of insulinomas, 90% are solitary and nearly 100% are intrapancreatic. A commonly held belief is that once the diagnosis of autonomous hyperinsulinism is confirmed, it is necessary to secure as much information as possible about the precise location prior to surgery. Although frequently used, preoperative localization studies are expensive, potentially morbid, and worse yet, may be misleading. We present a case study in which the preoperative studies falsely localized the insulinoma to the pancreatic head. Since the introduction of intraoperative ultrasound (IOUS), it is now unusual not to identify and excise the insulinoma in patients undergoing exploration for functioning beta-islet cell lesions. Our experience, along with support from the literature, led us to recommend a simplified localization approach, namely IOUS combined with surgical palpation. PMID- 7781810 TI - Medullary cell carcinoma of the thyroid: metastases to the central nervous system. AB - We document a case of a patient who had been treated for a medullary cell carcinoma of the thyroid three years previously and who presented with a three month history of ataxia, weakness and headache. A CT scan showed contrast enhancing lesions in the posterior fossa. An MIBG uptake scan showed that there was some uptake in the cerebellar lesions; however, it was not sufficient to rely on this alone for treatment. The larger of these lesions was therefore surgically resected. Immunocytochemistry, using CAM 5.2, CEA and chromogranin, demonstrated a positive reaction which strongly favoured a diagnosis of metastases from a medullary cell carcinoma of the thyroid. However, absolute confirmation of the diagnosis was obtained using immunocytochemistry with calcitonin. Medullary cell carcinomas of the thyroid usually spread locally and metastasis to the brain has never before been reported. PMID- 7781811 TI - Sulphite analysis of food ingredients: false positive responses with butter flavourings in the optimized Monier-Williams method. AB - The analysis of commercial butter flavouring materials for sulphite by the optimized Monier-Williams method revealed detectable levels of apparent sulphur dioxide (1810 ppm for butter oil, 5760 ppm for butter flavour, and 14.5 ppm for butter derivative) even though the manufacturers claimed that no sulphites were used in processing these ingredients. The presence of volatile fatty acids in these ingredients may explain the anomalous results. Volatile fatty acids were found to interfere with the optimized Monier-Williams method for sulphite determination, detectable levels of titratable acid being found in the hydrogen peroxide trap with amounts of volatile fatty acids as low as 0.3 g. The levels of volatile fatty acids in foods would not be predicted to cause significant interference in the analysis of sulphite residues by the optimized Monier Williams method. However, this analytical procedure is not recommended for the analysis of sulphite residues in food ingredients containing substantial amounts of volatile fatty acids. Alternative methods for the detection of residual sulphite, such as the sulphite oxidase assay and the colorimetric para-rosaniline method, are not subject to interference by volatile fatty acids. PMID- 7781812 TI - 14C-sorbic acid distribution in the aqueous and non-aqueous extracts of cooked millet dough (fura). AB - Millet flour was used to prepare the West African food, fura, preserved with sorbic acid. The lipid and protein fractions which appeared to bind sorbic acid or its degradation products were identified with the help of 14C-sorbic acid. Fractionation of the lipids and proteins from fura showed the 14C to be associated with the petroleum spirit crude fat extract (28 +/- 5%), the water soluble (6.2 +/- 0.7%), the ethanol-soluble (4.5 +/- 0.7%), the salt-soluble (3.5 +/- 0.6%) and the acetic acid-soluble components (0.9 +/- 0.3%). Dialysis of the ethanol-, salt- and acetic acid-soluble fractions suggested that 14C activity tended to be associated with the low molecular weight components of these fractions. PMID- 7781813 TI - Development of multi-residue methodology for the HPLC determination of veterinary drugs in animal tissues. AB - The application of solid-phase extraction and HPLC with UV-diode array detection to the multi-residue determination of veterinary drugs is described. A two-stage SPE clean-up was employed, using C18 and silica cartridges. HPLC analysis was carried out on a base-deactivated C8 column using gradient elution systems at two pH values. The procedure establishes the basis of a method for routine screening of pig kidney samples for some sulphonamides, benzimidazoles, nitroimidazoles and nitrofurans at concentrations at or below the UK Maximum Residue Limits (MRLs). Limits of detection of 2-18 micrograms/kg could be achieved for these analytes at recoveries of 40-70%. UV spectra measured on-line were used for confirmation of peak identities at these concentrations. The possibility of extension of this procedure to a wider range of analyses is discussed. PMID- 7781814 TI - Determination of quinoxaline carboxylic acid (metabolite of carbadox) in animal tissue by HPLC. AB - A method for the determination of residues of quinoxaline-2-carboxylic acid (QCA), the major metabolite of carbadox, in pig kidney has been developed. Tissue samples were subjected to alkaline hydrolysis, liquid-liquid extractions, ion exchange chromatography and further extraction to concentrate the analyte and purify the extract. Determination was by reverse phase HPLC with UV detection at 320 nm. Validation exercises carried out on batches of six samples fortified with 0.050 mg/kg QCA on three separate days gave mean recoveries ranging from 72 to 79% with relative standard deviations ranging from 5.6 to 7.8%. Samples fortified with 0.010 mg/kg QCA gave a mean recovery of 100% with a relative standard deviation of 9.8%. PMID- 7781815 TI - The effect of cooking on veterinary drug residues in food: 2. levamisole. AB - The heat stability of levamisole was investigated. Results obtained indicated that the drug was stable in boiling water at 100 degrees C, but unstable at 260 degrees C in cooking oil, with a half-life of about 5 minutes. The effect of cooking (microwaving, boiling, roasting, grilling and frying) on levamisole residues in a range of fortified and incurred tissue was studied. No evidence of instability was obtained in any of the cooking methods investigated. Most observed net changes fell within the limits of the precision of the method once allowance for weight loss during cooking was made to counter an apparent increase in concentration. Roasting was the only method of cooking where a net loss of levamisole was observed. Insufficient juices were produced to permit analysis in this instance. The net loss of levamisole in the cooked tissue was similar to that found with other cooking methods, where the levamisole lost was found in the cooking liquid or juices. An assessment of homogeneity of the incurred tissue used in the investigation was made. The pig muscle was found not to be homogeneous with larger differences seen between different areas of the animal than within the same muscle. The findings of this investigation showed that data obtained from measurements on raw tissue are suitable for use in consumer exposure estimates and dietary intake calculations. PMID- 7781816 TI - Evaluation of herbicide migration from water to gorgonzola and mozzarella cheeses in industrial processing. AB - The possibility of migration of atrazine, simazine, terbuthylazine, molinate and bentazon herbicides from contaminated water used in the manufacture of gorgonzola and mozzarella cheeses was verified in an industrial plant in an agricultural area in northern Italy. In a milk-processing plant, water samples were drawn from five wells; samples of milk, curd and finished products were collected from the respective production lines. In all samples, the herbicide residues were detected by gas chromatographic analysis. The results show that herbicide residues detected in water were not found in the finished products even if residues were found in the intermediate products (curd). PMID- 7781817 TI - Taste interaction of styrene/ethylbenzene mixtures in an oil-in-water emulsion. AB - Styrene and ethylbenzene are present in detectable amounts in polystyrene packaging materials and migration of these compounds may cause a taint of the packed food. The effect of mixtures of styrene and ethylbenzene on the detection threshold concentration in a 5% oil-in-water emulsion was investigated with the constant stimulus differences test. The detection threshold concentrations of the individual compounds in the emulsion were found to be 1.0 ppm for styrene and 3.0 ppm for ethylbenzene. Linear regression of the percentages of correct answers and the logarithm of the sum of the concentrations of both compounds in the mixtures expressed as fractions of their threshold concentration gave the following relationship: % of correct answers = 42.5 x log (sum of threshold fractions) +74.8 (r = 0.87). Calculation of the sum of threshold fractions at the 75% point of correct answers gave a value of 1.0, which clearly indicates that the effect of mixing of styrene and ethylbenzene is additive at sub-threshold levels in a 5% oil-in-water emulsion. PMID- 7781818 TI - Identification of potential migrants from samples of dual-ovenable plastics. AB - The analysis of samples of dual-ovenable cookware articles has identified chemicals with the potential to migrate into food. Samples were analysed by dynamic headspace analysis at 200 degrees C using a Tenax TA trap cooled in ice, and/or solvent extraction, followed by gas chromatography/mass spectrometry. Plastics analysed were crystalline poly(ethyleneterephthlalate) (cPET), thermoset polyester, poly(ethersulphone) and poly (4-methyl-pent-1-ene) (TPX). The greatest number and quantity of chemicals with the potential to migrate were found in thermoset polyester. PMID- 7781819 TI - Compositional analysis of samples of thermoset polyester and migration of ethylbenzene and styrene from thermoset polyester into pork during cooking. AB - The levels of ethylbenzene, styrene, benzene and benzaldehyde in samples of thermoset polyester were determined by dynamic headspace/gas chromatography. Styrene was present at levels from 50 to 1400 mg kg-1, ethylbenzene up to 25 mg kg-1 and benzaldehyde up to 180 mg kg-1. Benzene levels were usually less than 1 mg kg-1, but one article contained 19 mg kg-1. Levels of styrene dimers and trimers were estimated using size exclusion chromatography followed by gas chromatographic (GC) analysis and were present at approximately 100 mg kg-1 and 700 mg kg-1 respectively. The principal identified constituents of solvent extracts were stearic and palmitic acids, present at a combined level of nearly 1% by weight of the plastic. Styrene was shown to be produced by thermal depolymerization at temperatures of 175 degrees C and above. The migration of ethylbenzene and styrene into belly pork cooked in thermoset polyester dishes for 1.5 h at 175 degrees C was measured by Likens-Nickerson extraction of the cooked meat and GC/MS analysis of the extracts. Migration ranged from 6 to 2400 micrograms kg-1 for styrene and from < 6 to 34 micrograms kg-1 for ethylbenzene. PMID- 7781821 TI - PVC cling film in contact with cheese: health aspects related to global migration and specific migration of DEHA. AB - Following exposure to the food simulant olive oil for 10 days at 5, 20 or 40 degrees C a global migration ranging from 20 to 30 mg/dm2 was detected from a common 'low migration' PVC film plasticized with a mixture of di (ethylhexyl)adipate (DEHA) and a polymeric plasticizer. In a laboratory experiment samples of cheese of the types most commonly consumed in Denmark were wrapped in this 'low migration' PVC film using a procedure simulating the actual pattern of use in retail shops. After a storage time of 2 h at 5 degrees C the level of DEHA was 45 mg/kg of cheese, which after 10 days increased to 150 mg DEHA per kg of cheese, corresponding to an estimated specific migration of 12 mg DEHA/dm2 of cheese surface. Based on statistics on dietary habits it is concluded that the retail packaging of small portions of cheese even in a 'low migration' PVC cling film may lead to consumer intakes of DEHA close to or above the tolerable daily intake of 0.3 mg/kg body weight as defined by the EEC Scientific Committee for Food. Furthermore, it is stressed that measurements of global migration followed by uncritical use of reduction factors may result in erroneous evaluation of the suitability of DEHA-plasticized cling film for the packaging of fatty foods. PMID- 7781820 TI - Migration studies on fatty acid amide slip additives from plastics into food simulants. AB - Specific migration studies, using food simulants, have been conducted on a range of polymers which are used in food packaging and contain commonly used fatty acid amide slip additives. Migration levels using the test conditions (10 days at 40 degrees C) were found to depend primarily upon the food simulant and the polymer type, with the fat simulant and low density polyethylene giving the highest values in the range 1.8-3.1 milligrams of fatty acid amide per kilogram of simulant. Extremely low levels of migration, < 0.05 milligrams of fatty acid amide per kilogram of simulant, were found with aqueous food simulants for all plastics tested, and fat simulant with PVC and polystyrene plastics. PMID- 7781822 TI - Exposure of infants to aflatoxin M1 from mothers' breast milk in Abu Dhabi, UAE. AB - During a survey of the occurrence of aflatoxins in mothers' breast milk carried out in Abu Dhabi, involving 445 donors at the Cornich Hospital and the Al Nehyan Clinic for Maternity and Childhood, 99.5% of samples were found to contain aflatoxin M1 at concentrations ranging from 2 pg ml-1 to 3 ng ml-1. The mothers represented a wide range of nationalities, ages and health status and the opportunity was used to seek any correlation between these factors and the concentration of aflatoxin M1 in breast milk. The protein, fat and lactose contents of milk samples were also determined and the possibility of any correlation between any of these and aflatoxin M1 was studied. PMID- 7781823 TI - Lead and cadmium in some berries and vegetables on the Finnish market in 1991 1993. AB - In order to determine the present contribution of vegetables and berries to the intake of lead and cadmium in Finland major vegetable groups as well as strawberries and blackcurrants were collected from wholesale distribution centres, orchards and the food industry. Pooled samples were mixed to represent wholesale distribution centres, exporting countries or geographical regions. Lead and cadmium were determined after wet digestion in concentrated HNO3 using ETAAS with Zeeman effect background correction and 0.1% palladium for lead and (NH4)H2PO4 for cadmium matrix modification. The method of standard additions was used for the quantification. The mean lead and cadmium contents found were: iceberg lettuce 1.1 and 20.9, butterhead lettuce 4.5 and 12.2, Chinese cabbage 1.4 and 11.1, cauliflower 1.6 and 7.1, cucumber 0.7 and 0.6, carrot 5.9 and 24.6, tomato 1.5 and 1.5, leek 3.8 and 12.8, cabbage 1.3 and 3.1, paprika 3.1 and 5.3, potato 5 and 6 (domestic) or 5 and 31 (imported), strawberry 6.5 and 13.7, blackcurrant 12.7 and 1.4 micrograms/kg. The contents found in this study are the lowest reported so far in Finland and equal to or lower than those found elsewhere. PMID- 7781824 TI - Determination and confirmation of methyl p-hydroxybenzoate in royal jelly and other foods produced by the honey bee. AB - Methyl p-hydroxybenzoate (methyl paraben) in foods produced by the Honey Bee was determined by HPLC and confirmed by GC-MS. The compound was detected at a mean concentration of 22.3 +/- 6.8 mg/kg (between 14.2 and 31.9 mg/kg) in commercial royal jelly, but was not detected in honey, propolis or pollen lumps at the detection limit of 1 mg/kg. Fresh royal jelly collected from apiaries contained methyl p-hydroxybenzoate at a concentration of 20.3 +/- 4.7 mg/kg (between 12.5 and 31.7 mg/kg). These results indicate that the methyl p-hydroxybenzoate in royal jelly is not added but is a natural component. PMID- 7781825 TI - Philosophy of occlusion: past and present. AB - Controversy in a field usually stimulates research to find answers and to promote clinical excellence. Thus, differing ideas about occlusion relative to centrics, gnathology, TMD, occlusal adjustment, and periodontal therapy have led to a controversial body of literature; however, I think also it has led to better treatment for patients, regardless of whether, for example, the concept of point centric or freedom-in-centric is advocated. No one can practice dentistry without some concept of occlusion whether it is applied to one or two teeth or to complete mouth restoration. Although the work of committees to clarify terminology is quite appropriate, common usage, semantics, avoidance of confusion in the literature, and the ideological nature of the bias in science must be carefully considered. At times we learn from history that all ideologies need constant revisions; too often the need leads to changes by fiat rather than by virtue of research on problems that may actually exist in communication. PMID- 7781827 TI - Occlusion and functional disorders of the masticatory system. AB - Understanding the relationship between occlusion and functional disorders of the masticatory system is no easy task. This article explores the static, functional, and dynamic relationships of the occlusal condition to the signs and symptoms of masticatory dysfunction. Some possible relationships are discussed. PMID- 7781826 TI - Biomechanics of occlusion and the articulator. AB - The evaluation of the occlusion is important in prosthodontics and restorative dentistry because the occlusal surfaces of the teeth to be restored must be functional units of the patient's stomatognathic system. Specifically, the morphology of the cusps, fossae, grooves, and marginal ridges should support the mandible in the intercuspal position and where appropriate, during eccentric jaw movements and in functional activities such as mastication. Restored teeth should not interfere with mandibular function in mastication, speech, and swallowing nor should they transmit excessive force to the attachment apparatus or the temporomandibular joint either in the intercuspal or eccentric jaw positions or during movement. PMID- 7781828 TI - Trauma from occlusion. Periodontal concerns. AB - Application of the chronic disease model to IPD suggests that to be most effective, programs of prevention and treatment include measures to address as many of the identified risk factors as is possible. It remains to be determined if TO is involved in the initiation of IPD, for example, if individuals with TO are at greater risk for the development of IPD. There is evidence that TO is a risk factor in the progression of IPD. Tooth mobility is associated with and is a risk factor for increased attachment loss and increased bone loss in patients with periodontitis. Tooth mobility can be reduced by occlusal treatment. Clinical trials involving patients with periodontitis clearly establish that a better clinical periodontal attachment level response to treatment is obtained when occlusal adjustment is included as part of the treatment plan. Patients with advanced periodontal involvement benefit from occlusal treatment in terms of increased stability for the teeth and also in terms of oral comfort. Finally, There is no evidence that without occlusal treatment, periodontal patients who are in careful maintenance programs are more likely to suffer recurrence of IPD. PMID- 7781829 TI - Occlusion and prosthodontics. AB - Occlusion in prosthodontics is extremely important. Muscle dysfunction can interfere with prosthodontic restoration of occlusion. Occlusal interferences are the primary cause of the hyperactivity that cause muscle dysfunction. Occlusal interference can also place adverse stress on restorations and result in premature failures. Lateral stresses on restorations can cause cement failures, porcelain fractures, and solder joint failures. Our goal in prosthodontics is to restore occlusion that is occlusal interference free. This article gave an overview of how this can be done in phases. In Phase I, a diagnosis is made as to the presence or absence of muscle dysfunction. If it is present, the OIs are hidden. Occlusal splint therapy is needed to get rid of the muscle dysfunction so the OIs can be found. The occlusal splint diagnosis whether OIs are the cause of the dysfunction. The cure is to correct the occlusion. The restoration of the occlusion should be OI free. The various factors to consider in design and restoration of the occlusion were presented. After successful restoration of the occlusion, the recall appointments should include an evaluation of the occlusion. The PRI, COS, and clinical examination can all be helpful in diagnosing whether muscle dysfunction is developing and whether OIs are developing again as a result of the normal changes that can occur. Suggestions were made on how to slow these changes. This article was not meant to cover every aspect of prosthodontic occlusion in detail. The goal was to present an overview for readers to make a self-evaluation as to what areas of their practice might need to be improved to improve the restoration of the occlusion. All was not taught in dental school. As one practices and improves in skill, more knowledge and abilities must be sought through graduate and postgraduate education. Occlusion is too important for a successful practice and happy patients to be ignored. Time will make this obvious; however, the failures may be costly. The best approach would be to anticipate the failures and prepare yourself to reduce the risks. Occlusal interferences are truly the plague of dentistry. PMID- 7781830 TI - Trauma from occlusion. Restorative concerns. AB - Trauma from occlusion and restorative concerns may affect the tooth itself, the supporting structures inside and around the tooth's immediate structures, and the total articulating system, which includes the neuromuscular system, the temporomandibular joints, and other systems such as the impairment of hearing or vision and many other peripheral conditions. A thorough examination and a differential diagnosis procedure is essential to restore the health of the articulating system and reverse peripheral condition. This includes the ability to restore the individual tooth in its best anatomic position as a complement to the articulating system using all individual disciplines of dentistry in the finest abilities of treatment and the ability to share and distinguish the possible parafunctional habits and the need for behavioral understanding, support, and management to limit or lessen the wear and destruction of the individual tissues and to restore a healthier physical support. PMID- 7781832 TI - Occlusal principles in orthodontics. AB - Morphologic and functional requirements of the orthodontically treated occlusion are discussed in this article. In the past, orthodontic treatment has been viewed as both a cause and a cure for temporomandibular disorders. This article reviews the literature, orthodontic implications of occlusal appliance therapy, and case reports. PMID- 7781831 TI - Occlusion and restorative materials. AB - Undoubtedly, the materials used in conjunction with restorative dentistry have been changing over the years. Although restorative systems before the early 1960s have changed only moderately, the last two to three decades have witnessed some fairly dramatic developments. Composite resins, mercury-free alloys, quartz-free ceramics, and gold-reduced or gold-free alloys represent some of the more obvious introductions. Considerable information has been made available concerning their physical and mechanical characteristics; however, little has been published concerning their effect on occlusion and equilibration of the teeth. PMID- 7781833 TI - Examination and occlusal analysis of the masticatory system. AB - Analysis of the occlusion and function of the masticatory system should be part of a thorough examination of the patient. This is especially important when signs or symptoms of functional disturbances are present or when planning extensive occlusal restorations. This article has strived to present (1) indications for occlusal analysis; (2) how to perform occlusal analysis and diagnostic aids that can be helpful in occlusal analysis; and (3) how information gained through occlusal analysis can be used in differential diagnosis of the three most common functional disturbancies of the masticatory system: trauma from occlusion, parafunction, and TM disorders. PMID- 7781834 TI - Principles of stabilization bite splint therapy. AB - The stabilization bite splint is discussed with regard to design, delivery, and clinical procedures that contribute to conservative appliance therapy. Indications for stabilization bite splint therapy and a clinical case report are presented. PMID- 7781835 TI - Laboratory procedures for the fabrication of maxillary occlusal bite plane splint. AB - Clear communication between the dentist and laboratory technician is important for the production of quality work and the saving of valuable chair time at delivery. This article discusses the laboratory procedures used in the fabrication of occlusal bite plane splint. Traditional heat curing, microwave heat processing, and visible light curing techniques are discussed. PMID- 7781836 TI - Occlusal adjustment. AB - Only an overview of the techniques for occlusal adjustment has been presented. A more thorough explanation can be found in the text Occlusion by Ramfjord and Ash, on which most of this material is based. PMID- 7781838 TI - [New Editor-in-Chief at Diabetes and Metabolism]. PMID- 7781837 TI - Supportive conservative therapies for temporomandibular disorders. AB - Many modalities of conservative supporting therapies are available to dental professionals for the management of disorders of the masticatory system. This article discusses pharmacologic and physical agents useful in the management of masticatory dysfunction and external biofeedback. PMID- 7781839 TI - [Multicenter evaluation of the Nutri-Expert Telematic System in diabetic patients]. AB - Nutri-Expert is a system for self-monitoring and dietetic education, accessible through Minitel. A preliminary randomised evaluation of one hundred diabetic patients in the Midi-Pyrenees region showed that Nutri-Expert improved dietetic knowledge, dietary habits and metabolic balance. The aim of the present study was to show that the system can be successfully prescribed to patients by physicians outside the center which originated it, indicating the benefit of a wider use of Nutri-Expert, among the diabetic population. One hundred and fifty-five patients, recruited by six French centres of diabetology, used Nutri-Expert from their homes for six months. Clinical examination, tests of dietetic knowledge and biological tests, including lipid fractions, were carried out before and after six months of use. After six months, there was a significant improvement in the patients' dietetic knowledge and in some biological parameters. Nutri-Expert is thus useful even when prescribed by a centre other than the hospital which devised the system. It is an additional beneficial tool in the ambulatory management of diabetic patients. PMID- 7781841 TI - [Prevalence of microalbuminuria in French type 2 diabetics followed by their general practitioner]. AB - Microalbuminuria is a risk marker for cardiovascular morbidity and mortality in Type 2 diabetes. We studied microalbuminuria among French Type 2 diabetic patients in general practice, because we set-up a trial using cardiovascular events as end-points. Two thousand twenty four volunteer patients were studied for Urinary Albumin Concentration (UAC) during outpatient visit to general practitioners. The UAC was measured on first samples. If UAC was positive (> or = 20 mg/l), a second sample was requested. If UAC was positive two times, persistently elevated UAC was identified (micro or macroalbuminuria). Clinical characteristic, cardiovascular antecedents and risk factors were studied. One hundred five first samples were excluded due to urinary infection; 1,217 others displayed normal UAC (< 20 mg/l); 63.4%; group N), 557 microalbuminuria (20-200 mg/l; 29.0%, group mu), and 145 others macroalbuminuria (> 200 mg/l; 7.6%; group M). Among subjects with positive first sample, 26.5% had persistent albuminuria. There was no intergroup difference for age, but males were more frequent in groups mu or M than N (p < 10(-4)). Blood pressure and body mass index varied between groups. Smokers and alcoholic subjects were more frequent in groups mu and M than N (p = 0.037 and p = 0.0003 respectively), as were cases with myocardial infarction (p = 0.0026), lower limb arteritis (p < 10(-4)), and laser treated diabetic retinopathy (p = 0.0002). Antihypertensive treatments were taken by 61% of the subjects. Elevated UAC (micro or macroalbuminuria) is frequent among french Type 2 diabetic patients cared by their general practitioners, and is associated with a high cardiovascular risk profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781840 TI - Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology. AB - Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated. PMID- 7781842 TI - Cardiovascular autonomic neuropathy in diabetic patients with macular oedema. AB - We performed a case-control study to investigate the determinants of macular oedema in patients with diabetes mellitus. Patients with macular oedema (n = 20) were selected for study, together with a random sample of subjects without macular oedema (controls, n = 21). Both groups were similar for sex, type of diabetes, treatment and glycaemic control. Patients with maculopathy had higher systolic and diastolic blood pressure than controls (P < 0.006 and P < 0.03, respectively). Impaired renal function was proportionally higher in patients with maculopathy than in controls (60% vs 47%). Vibratory perception was more impaired in the maculopathy group than the control group (P < 0.02), and maculopathy was associated with the presence of cardiovascular autonomic neuropathy. R-R variation and the brake index were significantly lower in patients than control subjects (P < 0.01 for both). Moreover, the group with maculopathy had a greater fall in systolic blood pressure after standing than did the control group (P < 0.0001). Autonomic neuropathy may be associated with the development of maculopathy and retinopathy, although additional evidence is required to confirm this association. Conditions associated with high blood pressure may accelerate progression and aggravate maculopathy. PMID- 7781843 TI - Adjuvant therapy in recent onset type 1 diabetes at diagnosis and insulin requirement after 2 years. AB - Partial recovery of beta-cell function in type 1 diabetes is common after diagnosis by intensive insulin therapy. Residual beta-cell function can be improved by other therapies. Cyclosporin (CyA) and nicotinamide (NA), alone or in combination, can preserve this function, as indicated by the parameters of metabolic control (insulin dose, HbA1C). After suspension of CyA, insulin requirement returns to control values, suggesting loss of residual beta-cell function. The effects induced by withdrawal of NA after 1 year are not known. For the first time, we studied 27 type 1 diabetes patients treated with NA for 12 months and then followed up for 1 year after discontinuance of NA. Another 25 patients treated with NA + CyA and 28 control patients were followed up similarly. Insulin requirement doubled 12 months after discontinuance of NA or NA + CyA, becoming identical to that of controls. As patients showed HbA1C values similar to control subjects, it is likely that beta-cell function deteriorated after discontinuance of therapy. As NA is safer than other agents and its effects are beneficial, longer studies are warranted to investigate NA in prolonged treatments since this compound is also being considered for prevention of type 1 diabetes. PMID- 7781844 TI - Adhered platelet morphology in diabetes mellitus. AB - We compared the morphology of platelets obtained from diabetic patients in various stages of retinopathy and nephropathy with those of control patients. The platelets were collected on to polyethylene films, processed and observed under scanning electron microscopy. Different platelet morphologies were observed within the diabetic group, correlating with the severity of complications, whereas platelets appeared normal in the control group. After more extensive follow-up and comparative studies, these preliminary observations could provide another diagnostic tool for detecting and evaluating severe complications associated with diabetes. PMID- 7781845 TI - Mefloquine-associated hypoglycaemia in a cachectic AIDS patient. AB - Quinine and its isomer quinidine are well-known causes of iatrogenic hypoglycaemia, due to excessive insulin secretion. The situation is less clear regarding other anti-malarial quinine analogues. In particular, this adverse effect has never been described with mefloquine (Lariam). We report a case of hypoglycaemia after mefloquine therapy (1,500 mg over two days) for severe gastrointestinal cryptosporidiasis in a cachectic AIDS patient with protracted diarrhoea. Blood glucose levels, which were normal before treatment, dropped to 2.3 mmol/l within a few hours and were corrected by i.v. glucose infusion. Hypoglycaemia did not recur despite continued treatment. Rat islets of Langerhans exposed to mefloquine in vitro (10(-8) mol/l to 10(-3) mol/l) secreted significantly more insulin than control islets (up to 980 +/- 180 microU/ml/5 islets incubated with mefloquine 10(-3) mol/l, vs 20 +/- 4 microU/ml/5 untreated islets). Mechanisms and triggering factors of hypoglycaemia induced by mefloquine and some other anti-malarial quinine analogues are discussed. Clinicians who manage cachectic patients, particularly those with protracted diarrhoea and/or receiving anti-malarial drugs including mefloquine, should be aware of the risk of severe hypoglycaemia. PMID- 7781847 TI - [Mechanisms of the intracellular effects of insulin]. PMID- 7781846 TI - [Dyslipidemia in the diabetic patient. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases)]. PMID- 7781848 TI - [Fear of hypoglycemia and/or pseudo-acceptance: what are the obstacles to control of insulin-dependent diabetes in the adult?]. PMID- 7781850 TI - Endothelin--its possible role during pregnancy. PMID- 7781849 TI - Risk factors and their identification. First Part: What is a risk factor? AB - This series of three articles reviews the designs of studies which can be used to identify risk factors of a disease, here: diabetes or complications of diabetes. In the present issue of Diabete & Metabolisme, the first article of the series, we give the definition of a risk factor, along with measures of its force- relative risk and odds ratio, followed by the epidemiological definitions of the diseases: diabetes, coronary heart disease and hypertension. Risk factors are further discussed and we complete the discussion by some observations on the bias which can arise from a study or from its analysis, which can lead the researcher to the wrong conclusion. The three types of epidemiological studies which are used to determine whether factors are associated with a disease: observational or cross-sectional studies, cohort studies and case-cohort studies will be described in the second of the series in the next issue of the journal. Examples will be provided of each of these study types; their advantages and disadvantages will be discussed. In a third issue, the final paper will provide some examples of the study types and the identification of risk factors. The first examples involve diabetes and pancreatic cancer, the second birth weight and non-insulin dependent diabetes. Having found an association between a risk factor and diabetes, then we will discuss whether it can be considered to be a risk factor and if so and whether it is likely to be a cause of the disease. PMID- 7781851 TI - Fluorescent in-situ hybridization (FISH) as an aid to marker chromosome identification in prenatal diagnosis. AB - Five cases of supernumerary marker chromosomes were identified in prenatal diagnosis as derived from chromosomes 18, X, and Y. One unexpected finding was in a case where the PCR was positive for the SRY gene while fluorescence in situ hybridization was positive for two X centromeres. In another case with an X derived supernumerary marker the newborn was phenotypically normal. Two women with fetal mar(18) and mar(Xp) decided to terminate the pregnancy. The fifth pregnancy had a karyotype of 46,XX,-15,+der(15)t(Y:15)(q11,23;p13). A phenotypically normal girl was born at term. PMID- 7781852 TI - Turner's syndrome with sex chromosome mosaicism. AB - The increased risk of gonadal neoplasia in cases of Turner's syndrome with sex chromosome mosaicism and the presence of Y chromosome material emphasises the need for a diligent search and removal of the streak gonads. One such case is reported here. PMID- 7781854 TI - Shoulder dystocia and symphysiotomy. PMID- 7781853 TI - Successful term pregnancy after Mustard operation for transposition of the great arteries. AB - Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring. PMID- 7781856 TI - Fetal oxygenation at cordocentesis, maternal smoking and childhood neuro development. AB - OBJECTIVE: To assess the relationship between subsequent neuro-development and measurements in small for gestational age (SGA) fetuses, including oxygenation at cordocentesis. DESIGN: A longitudinal study of a cohort of SGA fetuses using those with normal oxygenation as controls. SUBJECTS: 65 chromosomally normal children aged 12-66 months who, as fetuses, had been small for gestational age, had undergone cordocentesis and had been delivered after 32 weeks' gestation. RESULTS: Griffiths' developmental quotient (DQ) was significantly associated with fetal blood pH (r = 0.41, P = 0.0008), PO2 (r = 0.25, P = 0.047) and PCO2 (r = 0.28, P = 0.027) at cordocentesis but not with the severity of growth retardation (r = 0.18, P = 0.17). However, the significant correlations between DQ and both PO2 and PCO2 were explained by their co-correlations with pH and neither remained significant after removing the effect of pH by analysis of variance. The association between DQ and pH was still significant after removing the effect of confounding variables. Maternal smoking during pregnancy was significantly associated with DQ (F to remove = 6.89, P = 0.011) even after allowing for the effects of possible confounding variables including fetal blood pH. CONCLUSIONS: Both fetal pH at cordocentesis and maternal smoking correlate significantly with subsequent neuro-development. Further investigation into the causes of these associations is required. PMID- 7781855 TI - Teenage pregnancy: are teenagers a high risk group? AB - OBJECTIVES: To study health profile of pregnant teenagers and their pattern of utilization of primary health care services in comparison with pregnant women aged 20-35 years in Abha, Saudi Arabia. STUDY DESIGN: A cohort of 1938 Saudi pregnant women (214 teenagers less than 20 years and 1724 aged 20-35 years) was selected by stratified random sampling technique. They were screened for anemia and hypertension using WHO criteria and followed until delivery to observe the method of delivery. RESULTS: The prevalence of anemia (9.6% and 12.0%, respectively) and hypertension (1.1% and 3.5%, respectively) was not significantly different among primigravida of both age groups. The same trend was observed among multigravida. Follow-up showed that the rate of abnormal deliveries among primigravida of both groups was not significantly different, and even lower among multigravida teenagers. Pregnant women in both groups had similar average prenatal visits (6.6 +/- 1.1 and 6.7 +/- 1.2 respectively, P < 0.05) and the majority contacted the primary health care center early in pregnancy (87.4% and 88.9%, respectively, P < 0.05). CONCLUSION: These results indicate that pregnant teenagers are not a high risk group if good prenatal care is provided. PMID- 7781857 TI - Effect of a prostaglandin E1 analogue (gemeprost) on uterine and luteal circulation in normal first trimester pregnancies. A Doppler velocimetry study. AB - OBJECTIVE: To evaluate the effects of gemeprost on utero-placental and luteal circulation and on the embryo/fetus in normal first trimester pregnancies. STUDY DESIGN: Sixty-seven women with a normal first trimester pregnancy requesting termination of pregnancy for psychosocial reasons were randomly allocated to pre operative treatment with vaginal suppositories containing placebo or gemeprost. The women underwent transvaginal color and spectral Doppler ultrasound examination before the application of the suppository, 4 h after the application of the suppository but before the abortion, and on the seventh post-operative day. Blood flow velocities in the uterine and subchorionic arteries, the intrachorionic area and arteries in the wall of the corpus luteum and the embryonic/fetal heart rate were measured. RESULTS: The median value for pulsatility index (PI) in the dominant uterine artery was 2.4 before treatment with gemeprost and 8.5 4 h after treatment (P = 0.0006); the corresponding values for time-averaged maximum velocity (TAMXV) being 27 cm/s and 10 cm/s (P = 0.0006). Four (14%) of 28 embryos/fetuses in the gemeprost group were dead 4 h after treatment with gemeprost and the median heart rate of those still alive was significantly lower than before treatment (130 vs. 163 bpm; P = 0.003). In the placebo group, the results for the uterine arteries and the embryonic/fetal heart rate did not differ significantly between the first and second ultrasound examinations. The median values for PI and TAMXV in the arteries of the corpus luteum wall at the first ultrasound examination were 0.71 and 18 cm/s, respectively, in the placebo group and 0.71 and 20 cm/s, respectively, in the gemeprost group. These values remained almost unchanged at the second and third ultrasound examinations in both groups. CONCLUSION: Gemeprost has profound effects on utero-placental circulation in the first trimester and can induce embryonic/fetal bradycardia and sometimes embryonic/fetal demise. It has no unequivocal effect on luteal circulation. PMID- 7781858 TI - Short-term results and long-term patients' appraisal of abdominal colposacropexy for treatment of genital and vaginal vault prolapse. AB - OBJECTIVE: To evaluate short-term results and long-term patients' satisfaction of abdominal colposacropexy performed for massive genital prolapse in our institute during a 14-year period. STUDY DESIGN: A retrospective analysis was performed of 101 consecutive women who underwent abdominal colposacropexy. The procedure consisted of retroperitoneal interposition of a Mersilene mesh between a prolapsed vaginal vault or uterus and the anterior surface of the sacrum. A questionnaire was used to evaluate patients' satisfaction after surgery. RESULTS: In the short-term there was an acceptable rate of complications of surgery, comparable with that reported in the literature. Prolapse-related complaints evaluated by questionnaire were markedly diminished after surgery. Pain and functional complaints were only partly improved in a subgroup of patients. Only 32% of the patients responded that they were fully cured after operation. CONCLUSIONS: Abdominal colposacropexy shows a particularly favorable result on prolapse-related complaints. Functional complaints and pain are not substantially relieved by this procedure. The complication rate of surgery is acceptable. PMID- 7781859 TI - Influence of hysterectomy on the fibrinolytic activity of plasma of women with intact ovarian function. AB - Hysterectomies are frequently required operations in gynecology. Several studies have reported an association between premenopausal hysterectomy and the risk of cardiovascular diseases. However, the pathophysiological linkages between these two conditions have not been elucidated. In recent years it has been shown that a decrease in plasma fibrinolytic activity is associated with increased risk of thrombosis. Furthermore, it has been known that the uterus is a very finbrinolytic active organ. In the present study we investigated the hypothesis that hysterectomy may lead to a decrease in plasma fibrinolytic activity, and thereby increase the risk for thromboembolic diseases. Fibrinolytic parameters of plasma were investigated in 26 women before and 6 weeks after premenopausal hysterectomy. Euglobulin lysis time (ELT), a global measure of plasma fibrinolytic activity, and the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were not different before and after hysterectomy. The ELT difference before and after venous occlusion, which is a good indicator for the risk of thrombosis, was also not significantly changed after hysterectomy. Estradiol-17 beta, progesterone, LH, FSH and sex hormone binding globulin displayed no significant changes after hysterectomy. Furthermore, the hormone measurements also indicated that the women were premenopausal. There were no correlations between the hormone values and fibrinolytic parameters. These data indicate that premenopausal hysterectomy does not lead to changes in plasma fibrinolytic activity. PMID- 7781860 TI - Reverse correlation between P-glycoprotein expression and proliferative activity in endometrial adenocarcinoma. AB - Immunohistochemical study was employed using a monoclonal antibody (C219) to investigate P-glycoprotein expression in 23 normal endometria and 40 endometrial adenocarcinomas. P-glycoprotein immunopositivity was observed in the mid- to late proliferative phase and the whole secretory phase of normal endometrium. In contrast, no P-glycoprotein was detected in endometrium of early proliferative phase nor post-menopausal endometrium. We also investigated the expression of P glycoprotein in endometrial cancers to find 16 out of the 40 endometrial adenocarcinomas (40%) expressed P-glycoprotein. P-glycoprotein immunopositivity was often observed in gland growing parts but not in solid growing parts in a given tumor specimen. Proliferative activity of the tumor, as measured by PCNA labeling, was significantly higher in the P-glycoprotein-negative group than that in P-glycoprotein-positive group (P < 0.005). Thus, there was a strong reverse relation between P-glycoprotein expression and proliferative activity in endometrial adenocarcinomas. PMID- 7781861 TI - Calcium metabolism, calcium supplementation and hypertensive disorders of pregnancy. AB - In recent years growing attention has been directed towards the possible role of calcium in the development of pregnancy-induced hypertension and preeclampsia. Several studies describe calcium metabolism in normal and hypertensive pregnancy, but so far, they have shown discrepant and inconsistent results. Intracellular free calcium, which plays an important role in vascular smooth muscle contraction, has been claimed as a pathogenic factor in hypertensive disorders of pregnancy. Although there is discordance in the data, a possible role of intracellular calcium in the development of hypertensive disorders of pregnancy cannot be excluded. Observational studies in pregnant women suggest an inverse association between calcium intake and the incidence of hypertensive disorders of pregnancy. Despite large methodological differences, the results from the calcium supplementation trials support this finding. Although it is rather difficult to isolate the effect of calcium intake from the intake of other mineral elements, results from calcium supplementation trials are supportive for calcium being the most important. Proposed mechanisms by which calcium supplementation may lower blood pressure involve changes in parathyroid hormone (PTH) level, the renin angiotensin system and calcium as a modifier of vascular agent regulation, but none of these have yet been elucidated. At present, circumstantial evidence suggest a positive role for calcium in the prevention of hypertensive disorders of pregnancy, but definite evidence is lacking and further research is warranted. PMID- 7781862 TI - Ovarian carcinoma serum markers and ovarian steroid activity--is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels. AB - In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8 9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed. PMID- 7781863 TI - Hormone replacement therapy: compliance and cost after screening for osteoporosis. AB - OBJECTIVE: To assess HRT compliance and cost 1 year after population screening for low bone density. DESIGN: Postal questionnaire sent out to women 1 year after having a bone density scan. MAIN OUTCOME MEASURES: Compliance with HRT, type of HRT and cost. RESULTS: Compliance with HRT after screening for women with low bone density was 48% for postmenopausal women and 59% for women with a simple hysterectomy. The most often used form of HRT was Estraderm (49%) for women with a hysterectomy, whilst for women with an intact uterus Prempak-C (54%) was the most popular. The average annual cost of treating women who had had a hysterectomy was 67 pounds whilst for women with an intact uterus it was 61 pounds, a non-significant difference. CONCLUSIONS: Approximately 50% of women with low bone density had started HRT within 1 year of having a densitometry examination. Previous reports of the cost advantage of treating women who had had a hysterectomy relative to those who had not has been overstated. PMID- 7781864 TI - A randomized, comparative trial of triptorelin depot (D-Trp6-LHRH) and danazol in the treatment of endometriosis. AB - To compare treatment efficacy and safety parameters a total of 55 premenopausal women with histologically proven endometriosis (stage II-IV) were randomized to receive the LHRH-analogue depot triptorelin (n = 30) or the steroid danazol (n = 25) for a total of 24 weeks. Immediately after cessation of the endocrine therapy a second-look operation was performed. Four as well as 24 weeks after the end of treatment patients were seen for re-evaluation of clinical symptoms and safety parameters. Estradiol suppression was significantly more pronounced with triptorelin, while the free androgenic index rose with danazol. Both substances were equally effective in reducing endometriotic implants (58% and 51%, respectively). Dysmenorrhea was absent at the end of medical therapy in both treatment groups. Dyspareunia and pelvic pain decreased at least by 50%. Red blood count, thrombocytes, liver enzymes and the atherogenic index rose with danazol, while the urinary calcium/creatinine ratio showed a marked elevation with triptorelin. Adverse effects were mainly due to the hypoestrogenism of the LHRH analogue and the androgenic/anabolic properties of the steroid. Triptorelin and danazol are equally effective in treating endometriosis. Therefore, choice of treatment should be based on the patient's medical history and the pharmacological profile of each substance. PMID- 7781865 TI - Integrins and reproduction. AB - The integrins are a large family of cell adhesion receptors, involved in cell cell and cell-matrix interactions. At present, 20 different integrin heterodimers are known. They not only anchor cells to their proper locations, but also activately mediate the passage of information into the cell. They are involved in such diverse processes as immune response, lymphocyte homing, platelet aggregation, metastatic spread of certain malignancies, healing process of tissue injuries and, embryologic development. The role of integrins in reproduction had been only recently suggested. Several reasons make these molecules very attractive, due to their constant involvement from egg to birth. A normal expression of integrins can disrupt every reproductive stage. Most likely diagnostic tools and therapeutic propositions will emerge from the knowledge of these receptors. Integrins are a family of membrane glycoproteines that mediate cell-substratum or cell-cell adhesion. In respect of one fundamental principle of cellular biology consisting of 'what a cell touches has a major role in determining what a cell does', adhesion has a main part in many cell functions. Adhesion not only anchors cells to their proper locations, but also activately mediates the passage of information into the cell. Cellular adhesion is implicated in the immune response, lymphocyte homing, platelet aggregation, metastatic spread of certain malignancies, embryologic development and wound healing. The role of integrins in reproduction appears interesting. The aim of this review is to introduce these molecules, to outline their roles in cellular function and to consider their involvement in reproduction before foreseeing their potential implications for therapy. PMID- 7781866 TI - Secretory leukocyte protease inhibitor in the cervical mucus and in the fetal membranes. AB - OBJECTIVE: The purpose was to determine the concentration of leukocyte elastase and SLPI in the cervical mucus plug, cervical tissue, fetal membranes, amniotic fluid and serum from pregnant women. STUDY DESIGN: Samples were analysed using radioimmunoassay, immunodiffusion, immunohistological and enzyme assay techniques. Statistical comparisons were performed by the Mann-Whitney two-sample rank sum test. RESULTS: Concentrations of SLPI and elastase in cervical tissue are significantly increased during pregnancy and after delivery. Very high concentrations of SLPI and elastase were found in the cervical mucus plug. The concentrations of SLPI and elastase in human fetal membranes are highest at the rupture site. The concentration of elastase in amnion from preterm delivery was significantly higher than in amnion from term deliveries. CONCLUSION: The high molar ratio of SLPI/elastase in the cervical mucus plug suggests that inhibition of elastase is important during normal pregnancy. The role of SLPI may be protection of the fetal membranes and cervical tissue. PMID- 7781867 TI - Decrease in perinatal mortality and increase in cesarean section rates. AB - OBJECTIVES: To investigate the cesarean section (CS) rate in the Riyadh area, its trend and relationship to perinatal mortality (PNM). METHODS: Based on delivery data obtained from the Ministry of Health hospitals, Saudi Arabia, for a total of 12 years, yearly rates of CS, PNM and the ratios of obstetricians and beds per 10,000 population were computed for the Riyadh area and compared with the overall rates for Saudi Arabia. Correlation coefficients were used to investigate the relationship between the CS rate and each of the stated variables. RESULTS: Riyadh had significantly lower rates of CS and PNM than Saudi Arabia as a whole. The CS rate in Riyadh showed a positive trend (increasing from 4.4 to 6.7%) while the PNM rate revealed a significant decreasing trend (decreasing from 21.6/1000 to 16/1000 live births). A negative association existed between the Riyadh rates of PNM and CS (r = -0.2375) and PNM and the availability of obstetricians (r = 0.8693). CONCLUSIONS: From our data it was not possible to establish a cause and effect relationship between the CS and PNM rates. PMID- 7781868 TI - Parity and the prevalence of overweight. AB - OBJECTIVE: To assess the association between previous term pregnancies and the prevalence of overweight in a group of urban women, controlling for the influence of age. METHODS: One thousand twelve women, living in middle and low socioeconomic areas of Mexico City, were interviewed at home and their reproductive histories studied. Height and weight were measured in a clinical setting using controlled procedures. Overweight (BMI > 25) was the dependent variable used to calculate odds ratios and to perform a multiple logistic regression analysis. RESULTS: Age and parity were significantly associated with the prevalence of overweight. Controlling for age, two or more previous pregnancies significantly increased the magnitude of the association. CONCLUSION: During the reproductive years parity seems to increase the risk of overweight in low and middle socioeconomic level urban women. PMID- 7781869 TI - Evaluation of combinations of procedures in cesarean section. AB - OBJECTIVE: To evaluate a procedure for cesarean section, consisting of a number of surgical techniques adopted from various sources and further developed. METHODS: The principal elements of the cesarean section procedure followed were: the Joel-Cohen method for opening the abdomen, suturing the uterus in one layer, and non-closure of the visceral and parietal peritoneal layers. The postoperative recovery of women who underwent this procedure (JCl--group) was compared with that of women who had undergone a Pfannenstiel incision, in which the uterus is sutured in two layers, and both peritoneal layers sutured (Pf2++ group). RESULTS: The incidence of postoperative febrile morbidity was 7.7% in the JCl--group compared with 19.8% in the Pf2++ group (P < 0.05). Adhesions were found in 6.3% of repeat operations after the JCl--operation compared with 28.8% after the Pf2++ operation (P < 0.05), and there was a non-significant trend toward fewer postoperative analgesics in the JCl--group. CONCLUSION: The cesarean section procedure we have devised is not only safe, but has a lower risk of long- and short-term complications. PMID- 7781870 TI - Perinatal and maternal mortality associated with retained second twins. AB - OBJECTIVES: The aim of this study of retained second twins admitted to Korle-Bu Hospital between 1988 and 1993 was to identify the factors contributing to the mode of delivery, perinatal and maternal mortalities, and draw up recommendations to improve outcome. METHODS: The study consisted of a review of record cards, outpatient admission and discharge books, delivery books, and inpatient case notes of women admitted with retained second twins of 28 weeks' or more gestation during the study period. RESULTS: Of the 65 cases fully reviewed, 33 (approximately 50%) were delivered by cesarean section due mainly to abnormal lie with or without shoulder impaction. The rest were assisted deliveries, mainly vertex deliveries or breech extractions. The perinatal mortality of the retained second twins was 38.5% compared with 12.3% for the first twins. Although in general the longer the interdelivery interval, the greater the second twin perinatal mortality risk, no clear direct correlation could be established. There was one perioperative maternal mortality due to anaphylactic reaction to intramuscular morphine injection. CONCLUSION: Irrespective of the antenatal course and early labor findings, twin delivery should be undertaken in a unit equipped for cesarean section and assisted delivery. The unacceptably high perinatal mortality of retained second twins could thus be significantly reduced. PMID- 7781871 TI - Efficacy of ipriflavone and 1 alpha vitamin D therapy for the cessation of vertebral bone loss. AB - OBJECTIVE: This study investigated whether a combined regimen of ipriflavone and 1 alpha vitamin D is effective in stopping postmenopausal bone loss. METHODS: Ninety-eight postmenopausal women were recruited and randomly assigned to one of four groups: group 1, ipriflavone alone; group 2, 1 alpha vitamin D alone; group 3, combined regimen of ipriflavone and 1 alpha vitamin D; group 4, no treatment. Vertebral bone mineral density, measured by dual energy X-ray absorptiometry, serum alkaline phosphatase, calcitonin, parathyroid hormone, osteocalcin, urinary calcium and hydroxyproline were measured before and at the 6th, 12th and 18th month of the study. All comparisons were made using Student's t-test of means. RESULT: There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy (mean loss after 18 months 0.33% in the combination group vs. 2.37%, 1.15% and 3.70% in the ipriflavone alone, 1 alpha vitamin D alone, and control groups, respectively; P < 0.001). CONCLUSION: These findings suggest that the combined regimen could prevent postmenopausal bone loss. PMID- 7781872 TI - Chromocystoscopy in the urological monitoring of patients with cancer of the cervix. AB - OBJECTIVE: To determine whether chromocystoscopy could be used for the urological monitoring of cervical carcinoma. METHODS: The absolute ejaculation time (AET, the interval of time between the intravenous injection of dye and the ejaculation of dyed urine in the bladder from either of the ureters) and the relative ejaculation time (RET, the difference of time between the two ejaculations) were retrospectively studied in relation to intravenous urography (IVU) and radionuclide renography (RR) in 141 patients. RESULTS: A significant probability of normal IVU and RR was found when the AET was < or = 7 min or the RET < or = 4 min and when no interval occurred between the two ejaculations. Pathological IVU and RR were found when there was no ejaculation from one or both ureters after 12 min. CONCLUSIONS: Chromocystoscopy could be used for monitoring cervical cancer patients. An abnormal chromocystoscopy could indicate the need for further radiological examinations. PMID- 7781873 TI - Spontaneous resolution of fetal mediastinal cystic hygroma. AB - We present a case of prenatally diagnosed mediastinal cystic hygroma with spontaneous resolution. To our knowledge, this is only the second case report of mediastinal cystic hygroma diagnosed prenatally, and the first one with spontaneous resolution perinatally. Our case shows that, in the absence of hydrops fetalis, mediastinal cystic hygroma in a fetus with normal karyotype can be associated with a normal outcome. Therefore we recommend fetal karyotyping, a careful search for other anomalies and close sonographic follow-up in such cases. PMID- 7781874 TI - Adenosarcomas originating from sites other than uterine endometrium. AB - We report three cases of adenosarcomas arising from extraendometrium of the uterus: one arising from the ovary, one from the paracolpium and one from the endocervix of the uterus. Microscopically, they consisted of an admixture of benign-appearing epithelial and mesenchymal components with hypercellularity and minimal atypia. Two of the tumors were initially misdiagnosed as endometriosis and one was diagnosed as adenofibroma. One patient had several recurrences and died 7 years after the initial laparotomy and another patient had sarcomatous overgrowth which invaded the muscular tissues of the large intestine. Thus it appears that adenosarcoma occasionally shows grave clinical behavior, despite the benign or low-grade appearance of its microscopic features. Problems of diagnosis and management of this tumor are discussed. An aggressive therapeutic approach including wide surgical excision is recommended even in questionable cases. PMID- 7781875 TI - Endometrial mullerian carcinosarcoma after cessation of tamoxifen therapy for breast cancer. AB - The aim of this report is to draw the attention of clinicians to the possible occurrence of endometrial cancers of rare histological type among women currently undergoing or having in the past undergone tamoxifen therapy, in particular for breast cancer. We report a case of heterologous mixed malignant muller tumor occurring in an 80-year-old woman. At 69, she had been diagnosed with breast cancer and received tamoxifen for a total of 55 months over a 6-year period. In the 5th year after cessation of tamoxifen therapy, an endometrial carcinosarcoma was diagnosed. Although the association between tamoxifen use and endometrial cancer is recognized, only a few reports of occurrence long after cessation of therapy exist. We believe ours is the second for this particular histological type. Tamoxifen may have played a role in the occurrence of this tumor although it is also known that this type of tumor may arise de novo in elderly women. The etiologic hypothesis obtained from this case description will now be tested in a formal epidemiological investigation which hopefully will provide more definitive evidence. PMID- 7781876 TI - Women in difficult circumstances: war victims and refugees. AB - The majority of problems that women are confronting today originate from a lack of respect for human and reproductive rights. Escalating war crises are producing an enormous number of civilian victims, of whom women and children comprise the major part. Rape used as a war tactic in Bosnia has proven to be a very powerful tool. War in Bosnia has provided a tragic incentive to work on strategies and tactics for reaching the victims in such chaotic and unpredictable circumstances. PMID- 7781878 TI - Adenomyomatous polyp of the uterus. PMID- 7781877 TI - The treatment of Bartholin's cyst and abscess with silver nitrate. PMID- 7781879 TI - Metronidazole during pregnancy. PMID- 7781880 TI - Reducing postpartum endometritis by intraoperative cervical dilatation. PMID- 7781881 TI - Axillary cystic lymphangioma in pregnancy. PMID- 7781882 TI - Fetal intestine and pulmonary maturity tests. PMID- 7781883 TI - ACOG technical bulletin. Diabetes and pregnancy. Number 200--December 1994 (replaces No. 92, May 1986). Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists. PMID- 7781884 TI - ACOG committee opinion. Antenatal corticosteroid therapy for fetal maturation. Number 147--December 1994. Committee on Obstetric Practice. American College of Obstetricians and Gynecologists. PMID- 7781885 TI - In memoriam: a remembrance of Marcus Singer. (1914-1994). PMID- 7781886 TI - Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics. AB - Lethal mutations in the giant discs (lgd) and fat (ft) tumor suppressor genes of Drosophila cause epithelial hyperplasia in all imaginal discs. By contrast, mutations in the vestigial (vg) gene adversely affect cell viability in the wing imaginal discs and consequently cause loss of pattern in the adult wings. However, combining homozygous lgd or ft mutations with homozygous vg1 increases the size of the wing imaginal discs and partially restores the bristle pattern in the wings of pharate adults. Comparable pattern restoration in vg1 wings is also induced by a newly isolated weak hypomorphic lgd3 allele. Further, mosaic analysis revealed that whereas lgd clones generated by the Minute technique display abnormal differentiation, those induced in a homozygous vg1 background exhibit autonomous restoration of wing pattern. These results suggest that pattern restoration in vg1 wings can serve as an assay for hyperplasia induced by mutations in Drosophila tumor suppressor genes. PMID- 7781887 TI - Bifunctional glyoxylate cycle protein of Caenorhabditis elegans: a developmentally regulated protein of intestine and muscle. AB - The reaction of an abundant 106-kDa polypeptide with a specific monoclonal antibody has been localized in intestinal and muscle cells of the nematode Caenorhabditis elegans. This protein was first detected in 4-6 cells of the clonal E lineage of 100-cell embryos. This lineage is committed to the intestinal cell fate. The antigen continued to be expressed in the differentiating gut and then appeared in early differentiating body wall muscle cells of 400- to 500-cell embryos. Molecular cloning and sequencing showed that the largest cDNA clone contained 3274 bp and encoded a sequence of 1005 amino acids. The predicted polypeptide of 112,799 MW contains separate domains for the glyoxylate cycle enzymes isocitrate lyase and malate synthase. Their enzymatic activities had been shown previously to be highest in embryos and L1 larvae (Khan, F. R., and McFadden, B. A. (1980). FEBS Lett. 115, 312-314; Khan, F. R., and McFadden, B. A. (1982). Exp. Parasitol. 54, 48-54; Wadsworth, W. G., and Riddle, D. L. (1989). Dev. Biol. 132, 167-173). The domain-specific sequences were shown to be contiguous in genomic DNA and are separated by an intron of 68 bp. A single polypeptide and both enzymatic activities are precipitated by the antibody, and peptide fragments resulting from limited proteolytic digestion contained amino acid sequences which overlap the predicted junctional region. The physical localization of the gene correlates with a small region of the left arm of Linkage Group V to which multiple embryonic lethal mutations have been mapped. PMID- 7781888 TI - Genetic regulation of shoot development in Arabidopsis: role of the EMF genes. AB - To investigate the genetic mechanism regulating Arabidopsis shoot maturation and development, we characterized eight emf mutants that bypassed the vegetative phase of the life cycle. Genetic complementation studies identified two EMF loci; both mapped to chromosome five. Double mutant analysis showed that the early- and late-flowering mutants, co, fb, elf1, elf2, and elf3, could not rescue vegetative development in the emf mutants, confirming the need for both EMF gene activities for rosette development. A series of phenotypes involving successive loss of reproductive organs was also observed in emf single mutants, in emf1-1/emf1-2 transheterozygotes, and in emf1 emf2 double mutants, suggesting that the EMF genes not only specify the rosette (vegetative) but also are involved in inflorescence and flower (reproductive) development. Phenotypic analysis of double mutants between emf and tfl1, lfy, and ag indicated interactions between EMF and genes regulating inflorescence meristem development and floral organ identity. A model depicting the role of the EMF genes in regulating shoot maturation and their interaction with genes that affect phase transitions is presented. PMID- 7781889 TI - Changes in the structure and function of the multicatalytic proteinase (proteasome) during programmed cell death in the intersegmental muscles of the hawkmoth, Manduca sexta. AB - The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta are a well-characterized model system for examining the biochemical changes that accompany programmed cell death during development. These giant muscles die during a 30-hr period in response to a decline in the circulating titer of the insect molting hormone 20-hydroxyecdysone. When the ISMs become committed to die, there are dramatic increases in both ubiquitin expression and ubiquitin-dependent proteolysis. Since the multicatalytic proteinase (MCP) is responsible for ATP/ubiquitin-dependent proteolysis in cells, we examined its composition and properties. The purified enzyme from whole larval integumentary tissues resembles MCPs isolated from other species with respect to subunit composition and general catalytic properties. However, when MCP was isolated from condemned ISMs, we observed an approximately ninefold increase in proteinase activity compared to MCP from precommitment muscles. This increase in proteolytic activity was correlated with an approximately eightfold increase in the absolute amounts of MCP protein as determined by Western blotting and densitometry. When purified MCP from condemned muscles was examined by two-dimensional polyacrylamide gel electrophoresis, four new subunits that were not detected in the precommitment muscles were present. Correlated with the addition of these new subunits was a dramatic increase in the levels of immunodetectable MCP throughout the cytoplasm and within the nuclei of dying muscles. These changes in MCP were regulated by the same hormonal signals that mediate cell death. These data are consistent with the hypothesis that when the ISMs become committed to die, more MCP accumulates in cells and new subunits are synthesized that change both the enzymatic properties and the conformation of MCP, which in turn participates in the dramatic proteolysis that accompanies cell death. PMID- 7781890 TI - Repression of gene expression at the beginning of mouse development. AB - The transition from maternal to zygotic gene expression in the mouse occurs in the 2-cell embryo. Previous studies in which DNA was injected into 2-cell embryos revealed that transcription promoters and origins of DNA replication are strongly repressed in cleavage stage embryos unless linked to an embryo-responsive enhancer. Repression also occurs when DNA is injected into the paternal pronucleus of a 1-cell embryo and the injected embryo subsequently undergoes mitosis, except that repression is no longer relieved by enhancers. Here we extend this observation to maternal pronuclei in 1-cell embryos and show that this repression could not be relieved either by linking the promoter to an embryo responsive enhancer or by inducing hyperacetylation of chromatin inorder to increase its accessibility to transcription factors. However, repression could be relieved by transplanting the injected pronucleus to a 2-cell embryo, even when the recipient cell subsequently underwent mitosis. Both the extent of promoter repression and the ability of enhancers to stimulate promoter activity increased as development proceeded from the early 2-cell stage to the 4-cell stage. Once repression was established in late 2-cell embryos, transplanting an injected 2 cell embryo nucleus back to an early 1-cell embryo failed to restore activity to the injected promoter, even when it was linked to an enhancer. These and other data demonstrate that cytoplasmic factors appear during formation of a 2-cell embryo that can repress promoter activity and activate enhancer activity. These factors are absent from the paternal pronucleus and cytoplasm of early (S-phase arrested) 1-cell embryos. Moreover, the cytoplasm of early 1-cell embryos appears to lack the ability to reprogram expression of genes once they have progressed to the late 2-cell stage in mouse development. PMID- 7781891 TI - Coexpression and promoter function in two muscle actin gene complexes of different structural organization in the ascidian Halocynthia roretzi. AB - During embryogenesis of the ascidian Halocynthia roretzi, 42 unicellular striated muscle cells are formed in the tail of the tadpole larva. Isolation of cDNA clones demonstrated that multiple genes for larval muscle actin are expressed in this process. Among them, at least five muscle actin genes (HrMA2, HrMA4a, HrMA4b, HrMA5, and HrMA6) form a cluster (HrMA2/4 cluster) within about 30 kb of the genome. The 5' flanking sequences of the five actin genes resemble each other. When constructs in which 184 bp of the 5' flanking region of each of these genes fused with lacZ were introduced into fertilized eggs, the reporter gene was expressed in muscle cells of the tailbud embryo, suggesting that the 5' flanking region of each cluster gene has promoter activity. In addition, a pair of muscle actin genes, HrMA1a and HrMA1b (HrMA1 pair), was isolated from a genomic region different from that of the HrMA2/4 cluster. The HrMA1a and HrMA1b are linked in a head-to-head arrangement on opposite strands and share a 340-bp 5' flanking sequence containing two symmetrically located TATA boxes. HrMA1a showed basically the same expression pattern as that of HrMA4a. When constructs in which the shared upstream region of HrMA1 pair fused with lacZ in either direction were microinjected into eggs, the reporter gene was expressed in muscle cells of the larval tail, suggesting a bidirectional promoter that regulates muscle-specific transcription of the HrMA1 pair. The tandem cluster of HrMA2/4 genes and the bidirectional promoter of the HrMA1 pair could expedite utilization of muscle specific trans-acting factors. The organization of genes in the genome may play an important role in the synthesis of a large amount of actins during the process of rapid differentiation. PMID- 7781892 TI - Biogenesis of the posterior-tail plasma membrane domain of the mammalian spermatozoon: targeting and lateral redistribution of the posterior-tail domain specific transmembrane protein CE9 during spermiogenesis. AB - We used immunoperoxidase histochemistry and confocal immunofluorescence microscopy to examine the events involved in the compartmentalization of CE9 to the posterior-tail plasma membrane domain during spermatogenesis in the rat. We identified two major episodes of spermatogenesis during which CE9 appeared to accumulate in relatively large amounts intracellularly within elements of the secretory pathway. The first episode encompassed cells from preleptotene through early pachytene primary spermatocytes and was evident as intense intracellular labeling of the endoplasmic reticulum and the Golgi complex. The second episode encompassed spermatids in steps 8-12 of spermiogenesis and was evident as intense intracellular labeling of the Golgi complex and smaller vesicular structures observed within the cytoplasm of the spermatid. Between these two episodes, CE9 was detected in considerably reduced amounts. Although present within the Golgi complex and the acrosomic system throughout much of the first half of spermiogenesis, CE9 was not detected on the tail of the spermatid until steps 8-9 of spermiogenesis. Although detected initially in relatively small amounts along the entire length of the tail beginning at steps 8-9, there was no evidence for the presence of relatively large amounts of CE9 on the tail or anywhere else on the surface of the spermatid until after step 11 of spermiogenesis. Between step 11 and steps 13-14 of spermiogenesis, CE9 was observed to accumulate in relatively large amounts on the whole tail coincident with its apparent loss from the Golgi complex. CE9 was observed to then undergo further compartmentalization to the posterior-tail domain sometime between steps 13-14 of spermiogenesis and spermiation. Our results suggest that CE9 is synthesized and enters the secretory pathway throughout much of spermatogenesis, but that the site of accumulation of CE9 varies considerably as a function of development. With respect to the biogenesis of the posterior-tail plasma membrane domain, our results suggest that CE9 is targeted from the Golgi complex to the plasma membrane of the whole tail during mid to late spermiogenesis and then redistributes laterally into the posterior-tail domain coincident with the caudal migration of the annulus late in spermiogenesis. This proposed pathway has a number of important implications for the logistical capabilities of the mammalian spermatid. PMID- 7781893 TI - Developmental regulation of troponin I isoform genes in striated muscles of transgenic mice. AB - The differentiation and diversification of striated muscle is a complex process involving numerous temporal and spatial alterations in the pattern of contractile protein isoform gene expression. In order to gain insight into the regulation of contractile protein isoform changes during skeletal and cardiac muscle formation, the expression of a transgene comprising a chloramphenicol acetyltransferase (CAT) reporter gene linked with sequences from -4200 to +12 of the human slow skeletal troponin I (TnIs) gene, and all three endogenous mouse troponin I (TnI) isoform genes, was investigated in embryonic, neonatal, and postnatal mice. The 4200 TnIsCAT transgene was properly activated in the limb and trunk skeletal muscle primordia and the early embryonic atrium and ventricle of the heart. Along with the endogenous mouse TnIs gene, expression of the CAT transgene began to segregate into the presumptive slow-twitch myofibers at late fetal stages and expression declined in the neonatal and postnatal heart except for the conductive tissues, in which expression persisted into adulthood. However, expression of the CAT transgene during development did not completely follow the endogenous mouse TnIs gene. The expression of the CAT transgene was aberrantly low in the embryonic cardiac outflow tract and the ventricles of the fetal heart. In addition to its expression in striated muscles, the transgene was expressed aberrantly in the primordial axial skeleton. We conclude that the upstream sequences from the human TnIs gene contain sufficient regulatory information to confer appropriate transgene expression during the early differentiation of skeletal muscles and during the establishment of fiber type upon the maturation of myofibers. However, additional regulatory elements are likely to be required for correct temporal and spatial regulation in the heart and somitic mesoderm during development. In vitro DNA transfection of cultured skeletal and cardiac muscle cells identified a cell type-specific enhancer element within the first intron of the TnIs gene whose absence in the transgene may account for the aberrant expression observed in vivo. In addition, we provide the first evidence that the fast-twitch skeletal muscle isoform of troponin I, TnIf, is transiently expressed during early cardiac muscle development. PMID- 7781894 TI - Epidermal growth factor ameliorates autosomal recessive polycystic kidney disease in mice. AB - C57BL/6J mice homozygous for the cpk gene exhibit an autosomal recessive (AR) form of polycystic kidney disease (PKD), similar to human ARPKD, with massive collecting duct cysts. These cysts are lined by epithelial with an immature phenotype. Since renal expression of epidermal growth factor (EGF) is also significantly decreased in affected mice, we hypothesized that renal EGF is necessary for normal developmental maturation of the collecting duct. To determine if the lack of EGF may be a decisive factor in the initiation and/or growth of collecting duct cysts, we administered exogenous EGF (1 microgram/g body wt subcutaneously) daily for Postnatal Days 3-9 (a critical period for collecting duct maturation) to C57BL/6J-cpk mice. EGF but not sham or albumin treatment retarded the development of PKD, reduced the degree of renal failure associated with the disease, and prolonged the survival of cystic mice. Sulfated glycoprotein-2 gene expression, a marker of immaturity in collecting duct cells, was reduced in cystic kidney by EGF treatment. This finding indicates that EGF treatment was associated with an increase in the maturation of the collecting duct epithelial cells. These findings support the view that decreased EGF may play a significant role in promoting the enlargement of collecting duct cysts in a hereditary model of ARPKD and that PKD involves defective and/or arrested collecting duct cell maturation. PMID- 7781895 TI - Expression and functional role of E- and P-cadherins in mouse mammary ductal morphogenesis and growth. AB - Mammary ducts, and the highly mitotic terminal end buds from which they are derived, consist of two layers of ectodermally derived epithelium, forming a tube within-a-tube structure. We investigated the role of Ca(2+)-dependent cell-cell adhesion molecules in maintaining the integrity of these layers. Immunostaining showed abundant E-cadherin on the lateral membranes of end bud body cells and ductal lumenal cells, but no P-cadherin. The basally located cap cells and their differentiated descendants, the ductal myoepithelial cells, displayed only P cadherin. We investigated the functional significance of this pattern of cadherin expression in situ by surgically implanting small, slow-release plastic implants releasing function-blocking antibodies. End buds exposed to a monoclonal antibody to E-cadherin showed disruption of the body epithelium, with epithelial cells floating freely in the lumen. Epithelial DNA synthesis, which is normally very high in these growth buds, abruptly declined. That this reduction in growth was not due to cell damage was shown by spontaneous reaggregation of the cells into a normal epithelium, with resumption of DNA synthesis, when the blocking antibody was depleted. A monoclonal antibody to P-cadherin had no effect on the lumenal layer but partially disrupted the basally located cap cell layer. These data indicate that spatially selective expression of E- and P-cadherins is required for mammary tissue integrity, which is in turn a prerequisite for normal rates of DNA synthesis. PMID- 7781896 TI - Two separate domains of laminin promote lung organogenesis by different mechanisms of action. AB - Laminin is a major component of basement membranes. We previously reported that the globular region of laminin B chain(s) and the cross region of the A chain play an active role in mouse lung branching morphogenesis. In this study, basic morphogenic cell behaviors modulated by laminin were analyzed in order to elucidate how this glycoprotein promotes lung development. Cocultures of epithelial and mesenchymal cells from mouse fetal lungs were used to determine the effect of site-specific monoclonal antibodies to laminin (AL-1, AL-2, AL-3, AL-4, and AL-5) on epithelial and mesenchymal cell adhesion, proliferation, and organotypic rearrangement. We found that monoclonal antibody AL-1, directed against the cross region of the laminin A chain, inhibited epithelial and mesenchymal cell attachment and had a selective antiproliferative effect on epithelial cells. In contrast, monoclonal antibody AL-5, directed against the globular region of the B chain(s), blocked epithelial cell polarity. Immunohistochemical studies on epithelial-mesenchymal cocultures exposed to monoclonal antibody AL-5 revealed the absence of laminin deposition at the epithelial-mesenchymal interface, whereas type collagen IV was present at this site. These findings suggest that each of the two laminin domains involved in lung development promotes morphogenesis by a different mechanism of action. The cross-region of the A chain mediates cell adhesion and epithelial cell proliferation, whereas the globular region of the laminin B chain(s) is critical for the process of basement membrane assembly and cell polarization. The combined effect of both laminin domains on epithelial and mesenchymal cells and on the interaction between them seems to be essential for normal lung branching morphogenesis. PMID- 7781897 TI - Characterization of two populations of ectopic cells isolated from the hearts of NGF transgenic mice. AB - We have observed sympathetic hyperinnervation and hyperplasia of an unknown cell population within the base of the hearts from transgenic mice in which nerve growth factor (NGF) expression was targeted to cardiac tissue (Hassankhani et al., 1993, 1995). To characterize this ectopic cell population, cells from the base of hearts of 3- to 4-week-old transgenic mice were dissociated and established in tissue culture, and their properties were analyzed using morphological, immunocytochemical, and physiological techniques. Morphological studies of the ectopic cells revealed the temporal expression of two different cellular phenotypes: (i) a spindle-shaped cell type, present by 1 to 2 days in vitro (DIV) and (ii) cells with a fiber-like morphology, detected by 7 DIV. In contrast to transgenic cardiac myocytes that express immunoreactivity to antibodies against sarcomeric myosin, beat spontaneously (approximately 60/min), and are electrically excitable, the ectopic cell types did not stain with an antibody against sarcomeric myosin, never showed contractile activity, and did not manifest membrane excitability. Moreover, these two types of ectopic cells demonstrated other distinctive characteristics. The spindle-shaped subpopulation typically formed small clusters of cells that were immunostained by antibodies to GFAP, vimentin, and low-affinity NGF receptor (LNGFR) and demonstrated a low incidence of dye coupling (30%), whereas the fiber-like cells aligned themselves along their long axes, immunostained for gp140trkA, LNGFR, and anti alpha-smooth muscle actin and showed extensive (100%) and diffuse dye spread to numerous other contiguous fiber-like cells. Dye spread was not observed between the adjacent fiber-like and the spindle-shaped cells and was reversibly blocked between homologous cells after treatment with halothane, a gap junction channel blocking agent. In comparison to cardiac myocytes, macroscopic junctional conductance of the spindle-shaped cells was more voltage-sensitive. At the single channel level, unitary junctional conductances of approximately 60 pS were predominant. Overall, these results indicate that these ectopic cells are likely derived from neural crest. The spindle-shaped cells appear to be immature Schwann cells, whereas the fiber-like cells may be related to the ectomesenchymal cells contributing to the morphogenesis of the cardiac outflow tract. PMID- 7781898 TI - Life stage and tissue-specific expression of the homeobox gene cnox1-Pc of the hydrozoan Podocoryne carnea. AB - We have isolated from the hydrozoan Podocoryne carnea a genomic clone and the corresponding cDNA of a homeobox gene. This gene, called cnox1-Pc, is most closely related to the lab class of homeobox genes. In the life cycle of P. carnea, which involves an asexually reproducing, sedentary polyp and a sexual planktonic medusa stage, we found cnox1-Pc transcripts specifically expressed in the medusa stage. Expression studies on isolated medusa organs and tissues indicate that the message is absent in the tentacles and the feeding and sexual organ of the medusa and present in the striated muscle cells. During medusa bud development, expression of cnox1-Pc can be correlated with the development of the striated muscle tissue, a cell type only found in the medusa. The results suggest that cnox1-Pc is involved in pattern formation of the medusa of P. carnea and might have a regulatory role in the differentiation of striated muscle. PMID- 7781899 TI - Induced premature G2/M-phase transition in pachytene spermatocytes includes events unique to meiosis. AB - Little is known about the control of events ending the lengthy prophase of meiosis I and leading to the G2/M-phase transition in mammalian spermatocytes, primarily because the relevant late pachytene, diplotene, and MI cells are present in low numbers in the testis and it is not possible to isolate them in significant numbers. We have utilized short-term cultures of pachytene spermatocytes from the mouse to study events of the G2/M cell-cycle transition induced by the protein phosphatase inhibitor okadaic acid (OA). Treatment of cultured pachytene spermatocytes with OA induced a rapid and premature onset of events leading to the M phase, visualized cytologically by nuclear envelope breakdown and chromosome condensation. After OA treatment, condensed chromosomes were seen as bivalents, not as univalents. Treatment with OA induced disassembly of synaptonemal complexes and resolution of crossovers as cytologically visible chiasmata. Chiasmata counts were similar in treated cells and control cells. Thus, surprisingly, even though the treated cells were in the pachytene substage of meiotic prophase, events of recombination were apparently completed to the point of chiasma formation in the majority of these cells. The sex chromosomes, forming the sex body of the pachytene spermatocyte, lagged behind the autosomal chromosomes in their condensation and progression toward the M phase. Treatment with OA induced an increase in histone H1 kinase activity, generally used as an indicator of metaphase-promoting factor (MPF) activity; furthermore, the OA induced cell-cycle transition does not require new protein synthesis. These results suggest that OA treatment overrides a cell-cycle checkpoint control that normally keeps pachytene spermatocytes in a lengthy prophase and that this control may be exerted by regulation of protein phosphorylation status. PMID- 7781900 TI - Drosophila midgut morphogenesis requires the function of the segmentation gene odd-paired. AB - Development of the Drosophila embryonic midgut is dependent on a number of genes, including tinman and bagpipe, which are required for formation of the visceral mesoderm, and the homeotic genes and their targets, which act locally in the visceral mesoderm to direct formation of specific midgut constrictions. Here we report the identification and characterization of another gene, odd-paired (opa), required for normal midgut development. opa, first identified by its pair-rule mutant phenotype in the larval cuticle, encodes a protein containing putative DNA binding domains and other hallmarks of transcriptional regulators. We have positively identified the cloned gene as opa by mapping two null mutations to the open reading frame of the putative opa transcript; these mutations disrupt the open reading frame and generate predicted proteins lacking the DNA binding domain. We demonstrate that opa function is required for formation of the three characteristic midgut constrictions. To understand the mechanisms by which opa contributes to constriction formation, we have analyzed the expression and function of opa throughout midgut development. In the cellular blastoderm, opa is expressed ubiquitously in the ectoderm and mesoderm precursors throughout the presumptive segmented region. As development proceeds, opa expression ceases briefly both in the ectoderm and in the underlying mesodermal cells that later become the visceral mesoderm. We show that in opa mutants the visceral mesoderm is interrupted, evidently due to abnormal expression of bagpipe, a homeodomain gene required for the formation of the visceral mesoderm. At early stages of development in opa mutants, interruptions in the visceral mesoderm are observed at many positions along the anterior-posterior axis. As development proceeds, interruptions are less frequently observed; however, one interruption, coincident with the Antennapedia expression and variability of Ultrabithorax expression in opa mutants. From these observations, we infer that the loss of at least the first and second midgut constrictions in opa mutants is the result of defects first evident in the early stages of visceral mesoderm development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7781901 TI - Colocalization of bFGF and the myogenic regulatory gene myogenin in dystrophic mdx muscle precursors and young myotubes in vivo. AB - Tissue culture studies using muscle cell lines suggest that in addition to mitogenic effects, fibroblast growth factors (FGF) inhibit skeletal muscle differentiation and the expression of members of a family of muscle-specific regulatory genes including MyoD and myogenin. We examined the possible coexpression of bFGF and myogenin by tandem in situ hybridization (detecting mRNA) and immunocytochemistry studies (detecting protein) to determine whether myogenic cells in vivo endogenously produce bFGF. Mdx mouse muscle, which shows characteristic dystrophic damage and regeneration, demonstrated mononuclear cells containing myogenin and bFGF transcripts in similar regions of adjacent sections of focal degeneration and repair, particularly near recent segmental fiber damage. Using immunocytochemistry and in situ hybridization concurrently on the same sections, bFGF protein and myogenin mRNA were colocalized in both muscle precursors and new myotubes. The in vivo results were confirmed in vitro using primary explant cultures of mdx muscle. Approximately one-half of mononuclear cells in vivo were myogenic by the criterion of myogenin mRNA expression. Both myogenin and bFGF mRNAs were also colocalized with bFGF protein, indicating endogenous expression of bFGF in a subpopulation of myogenic cells. Small numbers of myogenic mononuclear cells were differentiated, as determined by the presence of developmental myosin heavy chain protein (DevMHC). These cells and new myotubes also colocalized myogenin, DevMHC, and bFGF. Since bFGF and myogenin are colocalized in mpec and myotubes in vivo and in vitro, endogenous expression of bFGF is not mutually exclusive of myogenic regulatory gene expression, either before or after differentiation of the skeletal muscle phenotype. Such features of coexpression suggest an important and complex role for bFGF in muscle regeneration in vivo. PMID- 7781902 TI - Laminin is required for heart, somatic muscles, and gut development in the Drosophila embryo. AB - Laminin, an extracellular matrix glycoprotein, has been implicated in a wide array of biological activities. Its specific roles during development, however, remain to be elucidated. In this report we describe the specific contribution of laminin to histogenesis and organogenesis during Drosophila embryogenesis. In particular, the function of laminin during mesoderm development and morphogenesis was dissected by analyzing embryos deficient in laminin A chain alone or in both laminin A and B2 chains. We show that laminin function is not required for the early phases of mesoderm patterning and morphogenesis in embryos at the extended germ band phase (stage 11). However, laminin function is required for the proper morphogenesis of the heart, somatic mesoderm, and the gut during later stages of embryonic development. In laminin A-deficient embryos, the heart is "broken" as a result of dissociation of the pericardial cells. The somatic myotubes are defective and do not extend properly, and the ventral oblique muscles never reach their proper attachment sites. Finally, during midgut formation, the endoderm fails to undergo the initial columnar polarization in the absence of functional laminin. These studies indicate that the primary function of laminin is to provide structural support for the various cell types, thereby enabling their proper organization into the various organs. PMID- 7781903 TI - Heart development in Drosophila requires the segment polarity gene wingless. AB - Mesoderm induction has been studied in many systems and some of the factors involved have been identified. Although the heart is mesodermal in origin, the molecular basis of heart development is essentially unknown. The Drosophila heart is a simple tubular structure similar to the early heart tube in vertebrates. The homeobox gene, tinman, has been shown to be crucial for heart formation in Drosophila. Several genes with considerable sequence similarities to tinman are expressed in cardiac primordial tissue of vertebrates and are likely to be required for heart development of higher organisms as well. In addition to transcriptional control factors, heart development might also depend on inductive signals. Here, we demonstrate that the gene wingless (wg), which is known to specify segmental polarity and neuroblast identity in Drosophila, has a novel role in mesoderm development: wg function is specifically required for heart development. A temperature-sensitive mutation of wg was used to inactivate wg function during precise developmental time periods. Elimination of wg function for a short time period after gastrulation results in the selective loss of heart precursors, without significantly affecting the formation of the body wall or visceral muscles, although some pattern defects are observed. This developmental requirement of wg for cardiac organogenesis is distinct from its function in segmentation and neurogenesis. We conclude that wg signaling is a crucial component of heart formation. PMID- 7781904 TI - The larval optic nerve is required for the development of an identified serotonergic arborization in Drosophila melanogaster. AB - The larval visual system in the fruitfly Drosophila melanogaster consists of two bilateral clusters of 12 photoreceptor cells. These neurons send their axons in a fascicle, the Bolwig's nerve, toward the target area in the ventral lateral region of the brain hemispheres. We describe the development of a serotonergic arborization originating in the central brain found in the larval optic center in association with the larval optic nerve. This arborization is formed by processes from larval neurons born during embryogenesis. However, these neuronal processes do not reach their final destination, the larval optic center, until late in larval development. Using mutations that disrupt the connectivity and/or development of the larval photoreceptor cells, as well as mosaic analysis, we demonstrate that the innervation of the larval optic center by this serotonergic arborization depends upon contact with the larval optic nerve. PMID- 7781905 TI - Cellular polarity in ciliates: persistence of global polarity in a disorganized mutant of Tetrahymena thermophila that disrupts cytoskeletal organization. AB - Much of the cell surface on the ciliate Tetrahymena thermophila is covered by a polarized lattice of cytoskeletal structures that are associated with basal bodies of the ciliary rows. Unique structural landmarks, including an oral apparatus and contractile vacuole pores, develop before cell division in localized domains located, respectively, posterior and anterior to the transverse fission zone. All of these structures can be visualized by specific monoclonal antibodies. A single-locus recessive mutation, disorganized-A (disA), primarily affects the striated rootlets of the ciliary-row basal bodies and brings about a severe disorganization in the positioning and orientation of these basal bodies and associated cytoskeletal elements. Nonetheless, the new oral apparatus, contractile vacuole pores, and other unique structures appeared at or near their normal sites along the anteroposterior axis of disA cells, indicating that the positioning of these localized structures is not dependent on the integrity of the ciliary rows. Abnormalities were present in the details of construction of some of the localized structures and in aspects of cell shape that may be influenced by these details. In the main, however, analysis of disA mutant cells indicates that intracellular domains near the cell poles develop independently of the vectorial polarity of the ciliary rows. PMID- 7781906 TI - An extracellular matrix protein of jellyfish homologous to mammalian fibrillins forms different fibrils depending on the life stage of the animal. AB - A monoclonal antibody generated against the isolated extracellular matrix (ECM) of the medusa Podocoryne carnea M. Sars (Coelenterata, Cnidaria, Hydrozoa) stains a fibrillar component of the Podocoryne ECMs in immunohistochemical preparations. The antigen shows a different staining pattern according to the type of ECMs from the animals life cycle. In ontogeny the epitope first appears after gastrulation in the planula larva as single widely dispersed small fibrils, which later accumulate to form a dense meshwork in the larval ECM. The distribution of the antigen strongly suggests an important role of the molecule to cover the biomechanical needs of the animal. In immunoblots one band with a size of 330 kDa is detectable in the polyp ECM, whereas in the outer ECM of the medusa a 340-kDa band is observed. Both the 330- and the 340-kDa bands appear when probed on the inner ECM of the medusa or on ECMs of the larva. The antibody was used to isolate a cDNA clone from an expression library. The deduced amino acid sequence of this cDNA fragment reveals a molecular structure composed of tandemly repeated epidermal growth factor-like repeats interrupted by a second cystein-rich motif first found in the latent transforming growth factor beta binding protein. Comparison of the sequence to the data bases indicates < 40% identity to human fibrillins. The presence of fibrillin-like beaded microfibrils in the ECM of P. carnea is furthermore demonstrated by electron microscopy after rotary shadowing. Our results demonstrate for the first time the existence of this noncollagenous interstitial ECM protein in invertebrates and suggest that the structure and the function of fibrillin have been conserved during evolution. PMID- 7781907 TI - Time- and concentration-dependent response of the Drosophila antenna imaginal disc to Antennapedia. AB - The response of the antenna imaginal disc to ectopic Antennapedia gene expression was explored in a heat shock Antennapedia (hsAntp) transgenic strain and in strains doubly transgenic for hsAntp and downstream enhancer trap targets. The distal to proximal changes in morphological transformation in response to Antennapedia product at different developmental stages were correlated with changing expression patterns of transgene targets from antenna to leg-like patterns. Dose-response studies indicated changing thresholds of response to Antennapedia. At particular stages and doses of Antennapedia product, cell differentiation of leg bristles was uncoupled from transformation of the third antennal segment to tarsus. The results suggest that determination for bristle type does not depend on a prior determination decision for organ type. The results also provide an avenue for exploring the nature of "competence" at cellular and molecular levels. PMID- 7781908 TI - Protein synthesis increases after fertilization of sea urchin eggs in the absence of an increase in intracellular pH. AB - We have reevaluated the presumed requirement for an elevated intracellular pH (pHi) in the acceleration of protein synthesis which follows fertilization of eggs of the sea urchin Lytechinus pictus. Zygotes were transferred to sea water at a low pH (6.8) containing a permeant weak acid at times ranging from 5 min to as early as 30 sec postinsemination, to reverse or prevent the rise in pHi that normally ensues upon fertilization. Using the fluorescent pH probe 2',7' bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), we show that transfer of zygotes at 1 min or earlier after fertilization essentially blocks the rise in pHi. Under these conditions, both the incorporation of radiolabeled leucine into protein and the assembly of ribosomes into polysomes increase substantially (> 50% of control values). We also assessed leucine incorporation during incubation of eggs and zygotes in sodium-free sea water or sea water containing amiloride, two additional treatments that block the pHi rise. In the presence of amiloride, leucine incorporation increased upon fertilization, whereas little or no increase was observed in sodium-free sea water. We provide evidence that the low rates of leucine incorporation in sodium-free sea water result from the tendency for this experimental condition to lower the pHi to values significantly lower than the pHi in unfertilized eggs. These findings call into doubt the belief that the pHi rise at fertilization is a necessary prerequisite for the acceleration of bulk protein synthesis. These observations support the view that pHi is only one of several signals involved in the turn on of protein synthesis at the time of fertilization of sea urchin eggs. PMID- 7781909 TI - Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. AB - Vasculogenesis, the de novo formation of embryonic blood vessels from their angioblastic precursors in situ, is supposed to be under the control of polypeptide growth factors and their receptors. The receptor tyrosine kinase flk 1 and its high-affinity ligand vascular endothelial growth factor (VEGF) represent an endothelial specific signal transduction system expressed during embryonic vascular growth in the mouse. We have cloned the quail homologs of VEGF and flk-1 using PCR and have investigated their expression pattern in vivo. As shown by Northern analysis and reverse transcription PCR, VEGF and flk-1 mRNA (3.9 and 5.8 kb, respectively) were already present in the unincubated blastodisc at low levels and were largely upregulated during gastrulation at Embryonic Day 1. As detected by in situ hybridization, flk-1 mRNA was initially present in the entire mesoderm of Day 1 embryos but from Day 2 on was restricted to endothelial cells. At Day 2 VEGF was ubiquitously expressed in the embryo proper and was mainly restricted to the vascularized part (area vasculosa) in the yolk sac. Later on VEGF expression was detected in all organs. In the kidney VEGF mRNA was mainly localized to the glomeruli. This pattern of expression is consistent with the pattern found during mouse embryogenesis. We have recently established an in vitro model of vasculogenesis in which hemangioblastic precursors are induced in cell cultures from the unincubated quail blastodisc by basic fibroblast growth factor (bFGF) and give rise to blood vessels in vitro. Taking advantage of this in vitro model we examined whether FGF and VEGF act in concert during vasculogenesis. We found that the flk-1 receptor mRNA is dramatically upregulated within 24 hr upon the addition of FGF to quail blastodisc cell cultures. This inducibility in response to FGF is confined to the first 24 hr of culture. The early expression of the flk-1 mRNA may characterize the differentiation of hemangioblastic precursors from pluripotent epiblast cells which in vivo is initiated during gastrulation. Thus, the time course and the pattern of expression during embryogenesis in different species suggest a major role for the VEGF/flk-1 signal transduction system in vasculogenesis and angiogenesis. PMID- 7781910 TI - SpGCF1, a sea urchin embryo DNA-binding protein, exists as five nested variants encoded by a single mRNA. AB - Several Strongylocentrotus purpuratus gene cis-regulatory regions contain asymmetric C4 sequences which are core elements of target sites for a specific DNA-protein interaction. Blastula stage nuclear extract contains five proteins which specifically bind to these target sites, resulting in a characteristic pattern of complexes in gel mobility shift assays. We used automated affinity chromatography to purify a protein which binds to these sites and have isolated the corresponding cDNA. This protein, SpGCF1, is a novel sea urchin DNA-binding protein with no overall homology to proteins reported in the databases currently available. The DNA-binding domain of this protein was identified by a deletion analysis. As demonstrated both for protein translated in vitro and for bacterial protein expressed from a cDNA clone, a single SpGCF1 mRNA serves as a template for the synthesis of five DNA-binding polypeptides. We show that these five polypeptides are most likely produced by differential usage of a nested set of AUG start codons in the SpGCF1 cDNA and thus contain variable amounts of a proline-rich N-terminal domain. Since proline-rich regions often serve as transcriptional activation domains, the five SpGCF1 proteins apparently possess different "activation potentials." PMID- 7781911 TI - Autonomous, erythroid-specific DNase I hypersensitive site formed by human beta globin locus control region (LCR) 5' HS 2 in transgenic mice. AB - The human beta-globin locus control region (LCR) is composed of four erythroid specific, DNase I hypersensitive (HS) sites that are located 6 to 18 kb upstream of the epsilon-globin gene. The beta-globin LCR appears to have two major functions. First, the sequences "open" a chromosomal domain that includes the epsilon-, gamma-, and beta-globin genes and, second, the LCR directs high-level, erythroid-specific expression of each globin gene family member. An LCR subfragment containing only 5' HS 2 can confer these properties on a linked beta globin gene. To determine whether 5' HS 2 can form an erythroid-specific, DNase I hypersensitive site in the absence of a linked globin gene, a 1.9-kb DNA fragment containing this site was injected into fertilized mouse eggs and DNase I hypersensitivity was analyzed in the animals that developed. In 9 of 10 transgenic mouse lines, the human 5' HS 2 fragment formed a DNase I hypersensitive site in fetal liver but not in fetal brain. These results suggest that human 5' HS 2 can function autonomously to organize an open chromatin domain specifically in erythroid cells. PMID- 7781912 TI - The in vivo rate of glucose-6-phosphate dehydrogenase activity in sea urchin eggs determined with a photolabile caged substrate. AB - Some of the earliest metabolic changes after fertilization of sea urchin eggs center around the activity of the pentose phosphate shunt. We here report on the in vivo activity of glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of this shunt, as assayed with a photolabile (caged) analog of the substrate, glucose-6-phosphate (G6P). Caged G6P was synthesized from radiolabeled (5-3H or 1 14C) glucose and loaded into unfertilized sea urchin eggs by transient electroporation. Irradiation of these eggs (either before or after fertilization) photolyses the caged G6P, thereby pulsing the cell with 3H- and 14C-labeled G6P. The fluxes of G6P into glycolysis and the pentose shunt are calculated from the rates of oxidation of labeled G6P to 3H2O and 14CO2; since the turnover of the 6 phosphogluconate pool by 6-phosphogluconate dehydrogenase is nearly instantaneous (Swezey, R.R., and Epel, D. (1992) Exp. Cell Res. 201:366-372), the rate of 14CO2 production by the pentose shunt is equal to the flux of G6P through G6PDH. The data indicate that G6PDH activity is very low in unfertilized eggs, increases 184 to 427-fold by 2 min after fertilization, and then decreases to a value that is 74 to 209 times the unfertilized level (maximally 0.005 x 10(-8) units per egg in unfertilized eggs, 2.14 x 10(-8) units per egg by 2 min after fertilization, and 1.05 x 10(-8) units per egg by 20 min after fertilization). In spite of this substantial activation, the enzyme activity is considerably repressed; compared with activity in broken cell extracts, G6PDH at these developmental times operates in vivo at 0-0.003%, 0.52-1.21%, and 0.21-0.59%, respectively, of its potential activity. These results are discussed in terms of various hypotheses regarding the modulation of G6PDH activity by fertilization. These activity measurements relate well to other indices of in vivo activity. The major use of the NADPH shortly after fertilization is to produce H2O2, which is used as a substrate for fertilization membrane hardening; our data indicate that the NADPH that is produced by the pentose shunt activity is 30-70% of that required for this postfertilization generation of H2O2. PMID- 7781913 TI - Five Trk receptors in the zebrafish. AB - Using a homology-based cloning strategy we have identified five members of the Trk family in the zebrafish Danio rerio. They are homologous to the three mammalian Trk receptors in their conserved intracellular kinase regions and the organization of their extracellular regions. The five trk genes are differentially expressed in the developing brain, spinal cord, cranial ganglia, and retina. Full-length forms of three of the trk genes are expressed when neurons pioneer the major axon tracts, whereas the two other trk genes have a later onset of expression. Truncated transcripts and forms containing an extracellular juxtamembrane region insert were found. The degree of sequence variation and expression differences within the family suggest that each of the five zebrafish Trk receptors have a functionally distinct role. These findings demonstrate that the vertebrate Trk family is larger than previously appreciated. PMID- 7781914 TI - Early embryonic expression of XLPOU-60, a Xenopus POU-domain protein. AB - XLPOU-60 is a Xenopus POU-domain gene whose expression is tightly controlled during early development at transcriptional, post-transcriptional, translational, and post-translational levels. We report the expression pattern of the XLPOU-60 protein; it is first detectable in the stage V oocyte and accumulates rapidly following fertilisation, reaching a peak at the time of the mid-blastula transition. In the blastula, XLPOU-60 protein translated from injected synthetic mRNA enters nuclei. During gastrulation, both transcript and protein are rapidly down-regulated in a cell-autonomous manner; down-regulation is not dependent on cell-cell contact or induction by activin in an animal cap assay. For the mRNA, this down-regulation correlates with changes in the length of its poly(A) tail and is dependent on sequences in the untranslated regions of the transcript. On the basis of its protein expression pattern and known DNA-binding properties, we speculate that XLPOU-60 may play a role in the control of early transcriptional events in the Xenopus embryo. PMID- 7781915 TI - Monitoring development and pathology of Drosophila indirect flight muscles using green fluorescent protein. AB - We describe the use of a green fluorescent protein (GFP) reporter construct to monitor indirect flight muscle development in normal and mutant Drosophila melanogaster strains. We used polymerase chain reaction to amplify a portion of the Act88F actin gene that includes 1420 nucleotides of flanking DNA, the transcription start, first intron, and initiator codon, incorporating the fragment into the Drosophila germ line transformation vector pCaSpeR. We fused the fragment to the gene encoding green fluorescent protein of the bioluminescent jellyfish Aequorea victoria. We could detect GFP protein in transgenic strains and found that its accumulation, conveniently visualized in living flies using epifluorescence microscopy, was limited to the indirect flight muscles. GFP fluorescence can be used to visualize all stages of flight muscle development subsequent to myoblast fusion nad facilitates the detection of morphological changes in fibers caused by particular mutations. PMID- 7781916 TI - Answering hard questions; asking for more! PMID- 7781917 TI - Advocacy for basic biomedical research. PMID- 7781918 TI - The origins of the clonal selection theory of immunity as a case study for evaluation in science. PMID- 7781919 TI - The actin fold. AB - X-ray structure analysis of actin and of the NH2-terminal domain of the heat shock cognate protein Hsc70 has revealed an unexpected extensive structural similarity between these two molecules. Despite the absence of significant similarity of their amino acid sequences, both proteins share the same core architecture and a common nucleotide binding site resembling the structure of hexokinase. All three are ATPases or kinases and bind ATP in association with Mg2+ or Ca2+. The common fold consists of two alpha/beta domains, which are connected by a putative hinge with an ATP-binding site situated between the domains. Each domain contains a five-stranded beta-sheet of identical topology, which suggests that the molecules may have evolved by gene duplication. From a comparison of the three aligned structures, a fingerprint sequence of the adenine nucleotide binding pocket was derived, which predicted that members of the glycerol kinase family should also have a similar fold of their nucleotide binding domain. This was later confirmed when the X-ray structure was published. Data base search with a refined consensus sequence has retrieved other sugar kinases, as well as the prokaryotic cell cycle proteins FtsA, MreB, and StbA, and two Escherichia coli phosphatases. These proteins are predicted to possess a structure similar to actin in the common core region. As exemplified for actin, Hsc70, and glycerol kinase, the diversity of biological function is provided by the polymorphism of the loops joining the beta-strands and helices in the core region and by inserted domains that show high variability. PMID- 7781920 TI - Protein kinases that phosphorylate activated G protein-coupled receptors. AB - G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that specifically recognize agonist-occupied, activated G protein coupled receptor proteins as substrates. Phosphorylation of an activated receptor by a GRK terminates signaling by that receptor, by initiating the uncoupling of the receptor from heterotrimeric G proteins. Six distinct mammalian GRKs are known, which differ in tissue distribution and in regulatory properties. The intracellular localization of GRKs to membrane-bound receptor substrates is the most important known regulatory feature of these enzymes. Rhodopsin kinase (GRK1) requires a post-translationally added farnesyl isoprenoid to bind to light activated rhodopsin. The beta-adrenergic receptor kinases (GRK2 and GRK3) associate with heterotrimeric G protein beta gamma-subunits, released upon receptor activation of G proteins, for membrane anchorage. The recently-described GRKs 4, 5, and 6 comprise a distinct subgroup of GRKs. These kinases utilize distinct mechanisms for membrane localization, which are just beginning to be defined. All GRKs appear to play the same general cellular role of desensitizing activated G protein-coupled receptors, but utilize distinctly individual means to the same end. PMID- 7781921 TI - The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. AB - Hypoxia causes constriction in small pulmonary arteries and dilatation in systemic arteries. Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which pulmonary blood flow is controlled in the fetus and by which local lung perfusion is matched to ventilation in the adult. HPV reduces the flow of desaturated blood through underventilated areas of lung. Even though many vasoactive substances have been examined as possible mediators of HPV, these appear more likely to be modulators than mediators. Hypoxic contraction has been demonstrated in single pulmonary vascular smooth muscle cells (PVSMC). The ability to sense changes in oxygen tension is observed in PVSMC and type 1 cells of the carotid body. In both cells, hypoxia has been shown to inhibit an outward potassium current, thus causing membrane depolarization and calcium entry through the voltage-dependent calcium channels. In both cells there is evidence to suggest that changes in the redox status of the oxygen-sensitive potassium channel or channels may control current flow, so that the channel is open when oxidized and closed when reduced. The redox status may be determined by the effects of hypoxia on mitochondrial/peroxisomal function or on the activity of an oxidase similar to NAD(P)H oxidase. More studies are needed to precisely define the individual potassium channels responsive to hypoxia and to confirm the gating mechanism. In systemic arteries hypoxia causes an increased current through ATP dependent potassium channels and vasodilatation, whereas in the pulmonary arteries hypoxia inhibits potassium current and causes vasoconstriction. PMID- 7781922 TI - Targeted vectors for gene therapy. AB - Successful gene therapy requires not only the identification of an appropriate therapeutic gene for treatment of the disease, but also a delivery system by which that gene can be delivered to the desired cell type both efficiently and accurately. Reductions in accuracy will inevitably also reduce efficiency since fewer particles will be available for delivery to the correct cells if many are sequestered into nontarget cells. In addition, the therapy will have net benefit to the patient only if gene delivery is sufficiently restricted such that normal cells are left unaffected by any detrimental affects of bystander cell transduction. Here we review how currently available delivery systems, both plasmid and viral, can be manipulated to improve their targeting to specific cell types. Currently, targeting is achieved by engineering of the surface components of viruses and liposomes to achieve discrimination at the level of target cell recognition and/or by incorporating transcriptional elements into plasmid or viral genomes such that the therapeutic gene is expressed only in certain target cell types. In addition, we discuss emerging vectors and suggest how gene therapy delivery systems of the future will be composites of the best features of diverse vectors already in use. PMID- 7781923 TI - The pathway of allosteric control as revealed by hemoglobin intermediate states. AB - The energetics of hemoglobin cooperativity has been analyzed through the use of stable, partially-ligated intermediates. These studies revealed that the two dimeric halves of the tetramer are autonomous, leading to a Symmetry Rule that governs the relationship between ligand-binding and the T-->R quaternary switch: the R structure is favored over T only when ligands are bound to both dimers within the tetramer. A major feature of the Symmetry Rule mechanism is the generation of cooperative free energy by tertiary conformational constraints, which are formed within one dimeric half of the T-tetramer and released during the quaternary structure change to R. These rules of tertiary and quaternary molecular switching also govern the roles of the heterotropic allosteric effectors (e.g. Bohr protons). PMID- 7781924 TI - Calcium-mediated cell injury and cell death. AB - The effect of intracellular ion deregulation, particularly of [Ca2+], on the events following acute cell injury and the progression of change from initiation (reversible) to maintenance (reversible-irreversible) phases and finally to cell death has been the major thrust of experimentation in our laboratory for over 20 years. Cell death, which plays an important role in both normal and pathological phenomena, has been classified into two principal types, accidental and programmed. Recent exploration of programmed cell death (or apoptosis) has revealed extensive data showing it is an important mechanism for the normal maintenance and also differentiation of a variety of cell types and organs. From the results from our laboratory and those of others, we continue to expand and refine our working hypothesis: deregulation of [Ca2+] results in a number of phenomena from activation of signaling mechanisms and alterations in cellular structure to alterations in gene expression, all of which contribute to or play a critical role in cellular toxicity, including carcinogenesis and cell death. Therefore, although much more experimentation is needed to clarify some of these phenomena, the implications of such data for understanding the mechanisms and processes involved in carcinogenesis and the chemotherapeutic killing of cancer cells are extremely exciting. These relationships between [Ca2+], cell injury, and cell death are briefly reviewed here within the framework of our hypothesis. PMID- 7781925 TI - Retinoid-binding proteins: structural determinants important for function. AB - The transport and functions of biologically active naturally occurring retinoids (Vitamin A, retinol, and its metabolites) are mediated by extracellular, intracellular, and nuclear proteins. X-ray crystallographic studies to date on the extra- and intracellular proteins have helped to define distinct protein retinoid recognition mechanisms, each with a characteristic structural motif. The extracellular proteins (serum retinol-binding protein and a retinoic acid-binding protein from rat epididymis) bind retinoids with a hand-in-glove like fit in deep, hydrophobic-binding cavities. The intracellular proteins (cellular retinol binding proteins types I and II) encapsulate the ligand in an aqueous internal cavity. The details of the mechanisms of retinoid recognition, and how they result as a consequence of the different protein structures, are described in this review. PMID- 7781927 TI - Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. AB - HIV-infected individuals and SIV-infected rhesus macaques have, on the average, decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels. We now show that a depletion of intracellular glutathione in a human T cell line (Molt-4) inhibits the activation and nuclear translocation of the transcription factor NF kappa B, whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of NF kappa B. Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and GSSG can be shown to inhibit the DNA-binding activity directly in cell-free systems, our studies suggest that GSSG is a physiologically relevant inhibitor in intact cells also. NF kappa B controls many immunologically important genes, so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine. PMID- 7781926 TI - Nutritional impact on the final outcome of liver injury inflicted by model hepatotoxicants: effect of glucose loading. AB - Fifteen percent glucose in drinking water for 7 days increased lethality of four structurally and mechanistically different model centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform, and carbon tetrachloride) in male Sprague-Dawley rats (n = 10/group). A nonlethal injection of thioacetamide was lethal in glucose loaded rats and therefore was chosen for further studies. Serum enzyme elevations and liver histopathology revealed that actual infliction of liver injury peaked between 36 to 48 h after thioacetamide injection; however, the liver injury progressed in rats receiving glucose, whereas it regressed in rats maintained on normal diet and drinking water without glucose supplement. Glucose loading did not increase the hepatic microsomal cytochrome P450. [3H]thymidine incorporation studies along with proliferating cell nuclear antigen immunohistochemical analysis of liver sections revealed inhibition of S-phase stimulation and decelerated cell cycle progression. These findings suggest that glucose loading inhibits cellular regeneration and tissue repair resulting in accelerated progression of liver injury inflicted by thioacetamide culminating in increased death of animals receiving a moderately hepatotoxic dose of thioacetamide. PMID- 7781928 TI - Morphogenesis of calcitic sponge spicules: a role for specialized proteins interacting with growing crystals. AB - Crystals formed in biological tissues often adopt remarkable morphologies that are thought to be determined mainly by the shapes of the confined spaces in which they grow. Another possible way of controlling crystal shape, demonstrated only in vitro, is by means of specialized proteins preferentially interacting with certain crystal faces. In so doing, they reduce the rate of growth in these directions and consequently change the overall crystal shape. In an X-ray diffraction study of the distribution of defects within the lattice of calcite crystals produced by certain sponges, we show that a remarkable correlation exists between the defect patterns or crystal texture and the macroscopic morphology of the spicules. This was observed in two cases in which proteins are present within the spicule crystal, but not in a third case where such intracrystalline proteins are absent. Furthermore, one of the spicules exhibited marked differences in texture even within families of structurally identical crystal planes, demonstrating that the organisms exert exquisite control over the microenvironment in which crystals grow. We conclude that highly controlled intercalation of specialized proteins inside the crystals is an additional means by which organisms control spicule growth. PMID- 7781929 TI - Preservation of the functional advantage of human time structure. AB - Upon exposure to sustained and synchronized diurnal activity, most human variables exhibit rhythms with a 24 h period. The best-fitting cosine curve to the data with a selected period (24 h) may yield parameters like acrophase (estimated peak time), amplitude, and mesor (rhythm adjusted mean). The sequential array of the rhythms' acrophases constructs the temporal order. Analyzing 168 different human rhythms revealed a time-dependent distribution with regard to the number of acrophases/h and to the clustering of variables according to function. Rhythms' amplitude/mesor ratios yielded a five modal distribution. The modes occurred at those clock times where repetitive habitual signals are anticipated. It is assumed that these specific features evolved to optimize the adaptive value of the temporal order. PMID- 7781932 TI - Gerontogenes: real or virtual? AB - The view that the life span of an organism is intrinsically limited and is largely species-specific necessarily involves certain notions of genetic elements of regulation. The term gerontogenes refers to any such genetic elements that are involved in the regulation of aging and life span. The existence of genes for programmed aging is generally discounted on the basis of evolutionary arguments against the notion of the adaptive nature of aging. It is suggested here that the concept of gerontogenes be linked with the idea of genes involved in homeostasis and longevity assurance, which is not contradictory to the nonadaptive nature of aging. Because these genes were not originally selected as real genes for aging, their involvement in aging is an emergent property making them virtual gerontogenes. Some experimental evidence is available that suggests that sets of genes involved in the maintenance and repair of various cellular functions are the primary candidates qualifying as virtual gerontogenes. PMID- 7781931 TI - Measurement of mRNA levels in tumor xenografts with quantitative autoradiography and in situ hybridization. AB - In situ methodologies allow qualitative and semi-quantitative analysis of spatial gene expression in whole organisms or tissues. We have applied quantitative autoradiography to in situ hybridizations of sections from human breast tumor xenografts to measure mRNA levels for ornithine decarboxylase, estrogen receptor, transforming growth factor alpha, and glyceraldehyde-3-phosphate dehydrogenase. Comparisons of control and tamoxifen-treated animals show significant decreases in MCF-7 tumor estrogen receptor mRNA levels in the drug-treated animals. Combining quantitative autoradiography with in situ hybridization allows measurement of absolute rather than relative mRNA levels for genes of interest, and to monitor effector-induced changes in these mRNAs in vivo. PMID- 7781930 TI - Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women. AB - Regional fat distribution is an important determinant of insulin resistance in obesity. In the current study, the relationship between skeletal muscle insulin sensitivity, mid-thigh muscle composition, and the metabolic profile of muscle was investigated. Muscle composition was assessed by computed tomography of the mid-thigh, and by activities of marker enzymes of aerobic-oxidative and glycolytic pathways and muscle fiber typing using biopsies of the vastus lateralis muscle. Muscle with reduced Hounsfield attenuation on computed tomography scans was increased in proportion to obesity, and was strongly related to insulin resistance, reduced muscle oxidative capacity, and increased anaerobic and glycolytic capacities by muscle. These findings suggest that as part of its expression of insulin resistance, skeletal muscle of obese individuals is also poorly equipped for substrate oxidation and manifests increased storage of fat. PMID- 7781933 TI - The advent of paper chromatography. PMID- 7781934 TI - Authors and Editors of the world unite. PMID- 7781935 TI - [Acute alcoholic pancreatitis: an autonomous entity?]. PMID- 7781936 TI - Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial. AB - OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy. PMID- 7781937 TI - [Surgical treatment of severe ulcerous hemorrhages: predictive factors of operative mortality]. AB - OBJECTIVES: Multivariate analysis of operative mortality in patients with bleeding peptic ulcer. METHODS: Seventy-eight consecutive patients, who underwent emergency surgical treatment for bleeding peptic ulcer were reviewed retrospectively. There were 49 males and 29 females, with a mean age of 64.3 years, 2/3 of whom had associated medical disease. Surgical treatment was conservative in 63 cases: oversewing or ulcer excision, alone (n = 29) or associated with vagotomy (n = 34); and was radical in 15 cases: antrectomy+vagotomy (n = 10) or partial gastric resection (n = 5). RESULTS: There were 17 (21.8%) postoperative deaths and 19 (24.3%) bleeding recurrences. The causes of death included 9 bleeding recurrences, 7 organ failures and one duodenal leakage. On multivariate analysis, previous medical illness (cirrhosis or cardiac insufficiency (P < 0.001), shock at admission (P < 0.001), prolonged delay until surgery (P < 0.001), and bleeding recurrence (P < 0.001) were independently associated with increased mortality. In contrast, the type of surgical procedure did not influence postoperative mortality, whereas bleeding recurrence was more frequent in case of conservative surgery (P < 0.03) and anticoagulation therapy (P < 0.01). CONCLUSION: These results suggest that surgical treatment of bleeding peptic ulcer should be proposed early in high-risk patients. A radical procedure should be favoured since it reduces bleeding recurrence rate without increasing operative mortality. PMID- 7781939 TI - [Digestive visceral sensitivity. Methods of study in humans and physiopathological implications]. PMID- 7781938 TI - [Does acute alcoholic pancreatitis always reveal chronic pancreatitis?]. AB - OBJECTIVES: Whether acute alcoholic pancreatitis may occur without underlying alcoholic chronic pancreatitis is still a matter of debate. The aims of this study were to assess the frequency and delay of signs of alcoholic chronic pancreatitis in patients who had an alcoholic acute pancreatitis revealing a pancreatic disease. PATIENTS AND METHODS: From 1975 to 1993, all patients hospitalised for acute alcoholic pancreatitis as a first manifestation for a pancreatic disease and with follow-up > 2 years were included. Definite (pancreatic calcifications, mild to severe Wirsung duct abnormalities, histological or operative data) and probable (diabetes mellitus) diagnosis of chronic alcoholic pancreatitis was systematically searched for initially and during follow-up. RESULTS: Among 122 patients, 114 were included and 8 were excluded because of insufficient follow-up. A definite diagnosis of chronic pancreatitis was made in 101 patients (88.6%) (pancreatic calcifications: n = 71, mild to severe pancreatographic abnormalities: n = 19, histological data: n = 8, peroperative data: n = 3). In 61 patients, the diagnosis of chronic pancreatitis was made during the first year of follow-up and in 40 patients, the diagnosis was made after one year of follow-up. Diabetes mellitus occurred in 4 other patients (3.5%) in whom diagnosis of chronic pancreatitis was considered as probable. No signs of chronic pancreatitis were found in 9 patients (7.9%). CONCLUSION: Acute alcoholic pancreatitis is the hallmark of underlying chronic pancreatitis in 92.1% of patients. Acute alcoholic pancreatitis without underlying chronic pancreatitis either does not exist or is extremely rare. PMID- 7781940 TI - [Intraoperative systematic cholangiography in celiopscopic cholecystectomy]. AB - OBJECTIVES: Laparoscopic cholecystectomy has become the therapeutic gold standard in uncomplicated cases of cholelithiasis. This study evaluated the feasibility and the results of intra-operative cholangiography during laparoscopic cholecystectomy. METHODS: Intra-operative cholangiography was attempted in 126 consecutive patients undergoing laparoscopic cholecystectomy. Common bile duct stones were detected according to the following criteria: a) clinically (history of jaundice or pancreatitis); b) biologically (aminotransferase > 2 N, alkaline phosphatase > 2 N, total bilirubin > 20 mumol/L); c) ultrasonographically (diameter of the common bile duct > 12 mm, presence of gallbladder stones < 10 mm); d) calculation of the multifactorial score of Huguier. RESULTS: An intraoperative cholangiography was performed in 116 patients (92%), for a mean duration of 16 minutes (range: 9-25 min). Two anomalies of the biliary tree were detected. Ten common bile duct stones were detected (8.6% with 50% success of laparoscopic extraction). One false positive case had justified a surgical exploration of the common bile duct. The sensitivity of preoperative criteria was 80%. No morbidity or postoperative biliary complications were related to the intraoperative cholangiography. CONCLUSIONS: Routine intraoperative cholangiography should be systematically performed during laparoscopic cholecystectomy, providing anatomical information of the biliary tree and detecting, in 1.7% of cases, unsuspected common bile duct stones which could be treated during the same operative procedure. PMID- 7781941 TI - [Interobserver concordance of echographic semiology in liver cirrhosis]. AB - OBJECTIVES: The aim of this study was to evaluate the interobserver agreement of cirrhosis symptomatology. METHODS: Eight patients with cirrhosis (without ascites) and 23 patients with chronic liver disease without cirrhosis were included. Four observers (2 juniors and 2 seniors, with 1 specialist and 1 general radiologist in each group) independently evaluated video recordings. Agreement of 18 variables was calculated by using kappa index (k), intraclass correlation coefficient (r) and agreement proportion. Observer bias and poorly trained observers were also investigated. RESULTS: Liver: surface: k = 0.68, homogeneity: k = 0.25, span: r = 0.87, caudate lobe: r = 0.4 to 0.57 according to 3 dimensions, right lobe length: k = 0.33. Veins: portal diameter: r = 0.73, splenic diameter: r = 0.75; umbilical vein: presence: k = 0.19, diameter: r = 0.5; left gastric vein: presence: k = 0, diameter: r = 0.18; spleno-renal shunt: k = 0.41. Spleen length: r = 0.93. Presence of cirrhosis: k = 0.53. The mean agreement for the 18 variables was not significantly different between juniors (0.53 +/- 0.32) and seniors (0.40 +/- 0.38) but was significantly better in specialists (0.61 +/- 0.22) than in general radiologists (0.43 +/- 0.40; P < 0.05). CONCLUSIONS: Interobserver agreement of ultrasonography is good to excellent for the main characteristics of the liver, the main splanchnic veins and spleen but poor to fair for collateral vessels and the caudate lobe. Agreement for diagnosis of cirrhosis is good but should be improved by only selecting reliable signs or experienced echographists. PMID- 7781942 TI - [Mid-term failure of balloon dilatation treatment of antral stenosis induced by caustics]. AB - We report the case of an antral stricture following lye ingestion. The patient was treated by 3 dilations using a through-the-scope balloon dilator, initially with good results. One year later, the recurrence of the symptoms led to 2 other sessions of dilation without success and a partial gastrectomy was performed. The intensity of the gastric wall fibrosis on the surgical specimen, probably responsible for major motor impairment, accounts for the discordance between the good endoscopic result and the clinical failure. Endoscopic dilation of lye induced gastric strictures could be a temporary alternative to surgical resection because the gastric wall fibrosis blemishes the long-term functional result. PMID- 7781943 TI - [Pneumatosis cystoides intestinalis associated with Steinert disease]. AB - We report the case of a 63-year-old patient suffering from myotonic dystrophy, complicated with respiratory insufficiency, who presented a pneumoperitoneum without sign of peritonitis. Diagnosis of pneumatosis cystoides coli was based on CT scan evidence. Given oxygenotherapy and antibiotherapy, the patient rapidly improved. The association between the two affections has, to our knowledge, not been previously described. PMID- 7781944 TI - [Agenesis of the right lobe of the liver and portal hypertension]. AB - A case of agenesis of the right lobe of the liver associated with portal hypertension is reported. This uncommon feature was diagnosed by computed tomography which excluded secondary liver atrophy due to cirrhosis or tumour. The main pathophysiological hypothesis for agenesis and portal hypertension, exceptionally associated, is arrest of hepatic development during foetal life. PMID- 7781945 TI - [Drug-induced toxicity: good practices for publication]. PMID- 7781946 TI - [Drug-induced hepatotoxicity: ethics, pressures and publication]. PMID- 7781947 TI - [Evaluation of celioscopic fundoplication by intraoperative esophageal manometry]. PMID- 7781948 TI - [Eosinophilic ascites in cancer of the pancreas]. PMID- 7781949 TI - [Acute intestinal intussusception in an adult treated by celioscopy]. PMID- 7781950 TI - [Unusual lithiasis]. PMID- 7781951 TI - [Chronic myelomonocytic leukemia and Crohn disease]. PMID- 7781952 TI - Prevalence of irritable bowel syndrome in Motril (Spain) PMID- 7781953 TI - [Pseudoparasitism due to a small fluke in the liver]. PMID- 7781954 TI - [Digestive hemorrhage caused by rupture of esophageal varices: emergency endoscopic sclerotherapy under general anesthesia]. PMID- 7781955 TI - [The treatment of hepatitis B and C with interferon-alpha can induce or aggravate psoriasis]. PMID- 7781956 TI - [Re-evaluation of risk of colonic cancer in Crohn disease]. PMID- 7781957 TI - [Portal hypertension: value of combination of nitrate derivatives and beta blockers for better prevention?]. PMID- 7781958 TI - Increases in gill cytosolic corticosteroid receptor abundance and saltwater tolerance in juvenile coho salmon (Oncorhynchus kisutch) treated with growth hormone and placental lactogen. AB - Juvenile coho salmon (Oncorhynchus kisutch) were injected with one of two recombinant bovine hormones, growth hormone (bGH; 5.0 and 0.5 micrograms.g-1 body wt) or placental lactogen (bPL; 5.0, 0.5, and 0.05 micrograms.g-1 body wt) to determine the effect on growth, plasma cortisol concentration, cytosolic corticosteroid receptors (CR) in the gills, and the development of hypoosmoregulatory ability. One week following a single injection or six weekly injections of bGH or bPL, the fish were measured and sampled for CR concentration and Na+,K(+)-ATPase activity in the gills. Fish were also challenged with salt water (salinity 25%) for 24 hr to determine saltwater tolerance at the end of the 6-week treatment. Treatment with bPL and bGH significantly increased weight and length of the fish. The 0.05-micrograms bPL dose significantly elevated plasma cortisol concentration, whereas all other hormone treatments did not affect cortisol levels. bPL and bGH also significantly increased CR concentration and Na+,K(+)-ATPase activity in the gills. The perturbation in plasma sodium concentration was least in animals receiving the highest dose of bPL and the bGH treated animals following transfer to seawater. An increase in cytosolic CR by bGH and bPL may increase responsiveness of the gills to cortisol and partially account for the increase in Na+,K(+)-ATPase activity and greater ability to regulate plasma sodium in seawater as exhibited by the experimental groups. PMID- 7781959 TI - Vasotocin-sensitive adenylate cyclase in frog glomeruli. AB - Adenylate cyclase sensitivity to neurohypophyseal hormones was investigated in isolated glomeruli and in nephron segments microdissected from collagenase treated kidneys of Rana ridibunda. Vasotocin treatment increased adenylate cyclase activity in glomeruli and in collecting ducts and did not modify it in proximal convoluted tubules and in early and late distal tubules. In glomeruli, the hormonal stimulation resulted mainly in a decrease in the Km value for adenylate cyclase, which means a higher affinity for substrate (ATP) to the enzyme, whereas the response to forskolin was accounted for by increases both in affinity for substrate and in maximal adenylate cyclase velocity. The homologous neurohypophyseal hormones stimulated frog glomerular adenylate cyclase with the following rank order of affinities: hydrin 1 > or = AVT = AVP > or = hydrin 2 > OT > or = mesotocin > isotocin; structural analogs dDAVP, VDAVP, dVDAVP, and [Phe2,Orn8]VT had weak agonistic properties, [Thr4,Gly7]OT was inactive, and the antagonists OVTA, d(CH2)5Tyr(Et)2VAVP, and des-Gly9-d(CH2)5Tyr(Et)2VAVP inhibited hormone-induced enzyme activation with similar apparent inhibition constants. The vasotocin receptors triggering adenylate cyclase stimulation in frog glomeruli differ pharmacologically from V2 vasopressin receptors of mammalian kidneys and may also differ from V2-like vasotocin receptors of amphibian skin and urinary bladder. PMID- 7781960 TI - The stimulatory and inhibitory effects of dopamine on prolactin secretion in the turkey. AB - Dopamine (DA) was infused into the third ventricle of anesthetized laying turkey hens at various concentrations to determine its effect on both basal prolactin (PRL) levels and ongoing electrically induced PRL secretion. The infusion of DA at rates of 1.0 or 10.0 nmol/min resulted in dose dependent increases in plasma PRL. These infusions had no inhibitory effect on electrically stimulated PRL release. The infusion of DA at 100.0 or 500.0 nmol/min caused no stimulation of PRL secretion and totally inhibited the PRL response elicited by electrical stimulation of the medial preoptic nucleus. These results show that dopaminergic influences are involved in both stimulating and inhibiting avian PRL secretion and suggest possible biphasic actions of DA within the brain. PMID- 7781962 TI - Insulin-like growth factor-I in the plasma of two reptiles: assay development and validations. AB - Radioimmunoassays (RIAs) of insulin-like growth factor-I (IGF-I) in nonmammals are complicated by two problems: decreased specificity due to heterologous assays and assay interference from IGF binding proteins. We have developed and validated an RIA for the detection of IGF-I in reptilian plasma that circumvents these problems. Biochemical validations show parallelism between standard curves, plasma dilutions, and internal standards. Further, biological validations indicate that (1) plasma IGF-I levels are significantly reduced in nonreproductive, female American alligators (Alligator mississippiensis) with high plasma estradiol-17 beta concentrations compared to individuals with low plasma estradiol-17 beta concentrations and (2) plasma IGF-I concentrations are elevated in juvenile Trachemys scripta elegans turtles fed higher quality diets (defined by protein and energy content). These results provide impetus for future studies of IGF-I in reptiles. PMID- 7781961 TI - Abundant insulin-like growth factor-1 (IGF-1) receptor binding in fish skeletal muscle. AB - Insulin and insulin-like growth factor-1 (IGF-1) receptors were quantified in glycoprotein fractions prepared by wheat germ agglutinin-agarose affinity chromatography from skeletal muscle of several species of salmonid fish and carp. Insulin binding in fish skeletal muscle was lower than insulin binding found in rat. IGF-1-specific binding was two- to sixfold higher than insulin binding (16.0 +/- 3.0 versus 5.8 +/- 0.75%/50 micrograms glycoprotein in brown trout, 15.5 +/- 0.9 versus 2.2 +/- 0.5%/50 micrograms in coho salmon, and 39.7 +/- 7.6 versus 16.0 +/- 3.0%/50 micrograms in carp muscle). Specific IGF-1 binding in fish skeletal muscle presented values similar to those in rat muscle. IGF-1 receptor binding was, in addition, highly specific. Cold IGF-1 displaced radiolabeled IGF 1 binding in doses 100- to 1000-fold lower than cold insulin (ED50 of IGF-1 binding to carp receptor preparations was 0.24 +/- 0.04 nM when displaced with cold IGF-1 and 368 +/- 83 nM when displaced with insulin). On the other hand, cold insulin displaced radiolabeled insulin binding at concentrations 10- to 100 fold lower than cold IGF-1. Receptor tyrosine kinase activity was stimulated over basal values in a dose-dependent manner by both insulin and IGF-1, although IGF-1 was more potent than insulin. Basal rates of phosphorus transferred to the artificial exogenous substrate poly(Glu4:Tyr1) were similar in all salmonid species (200-320 fmol P/micrograms protein) and higher in carp (1840 +/- 300 fmol P/micrograms protein). Maximum percentage of stimulation of tyrosine kinase activity by insulin and IGF-1 was in the same range in all salmonid species and carp (130-200% for insulin, 160-232% for IGF-1). Abundance of IGF-1 receptors in fish skeletal muscle contrasts with the pattern observed in higher vertebrates, in which insulin receptors prevail over IGF-1 receptors. PMID- 7781963 TI - Nature and distribution of gonadotropin-releasing hormone (GnRH) in the brain, and GnRH and GnRH binding activity in serum of the spotted dogfish Scyliorhinus canicula. AB - The distribution of different molecular forms of gonadotropin-releasing hormone (GnRH) in the brain and serum of the spotted dogfish, Scyliorhinus canicula, was investigated by an indirect immunofluorescence method, using antisera against salmon (s-), chicken-II (cII-) and mammalian (m-) GnRHs, and by reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with radioimmunoassays. Five GnRH molecular forms were demonstrated on the basis of the retention time in the RP-HPLC system. The characteristics of four of these GnRH peptides are consistent with those of m-, cII-, dogfish (df-), and sGnRH. The fifth form appears to be novel. Immunoreactive sGnRH structures were confined to the diencephalon; whereas cIIGnRH and mGnRH were found in the telencephalon and diencephalon. cIIGnRH- and dfGnRH-like molecules were detected in the serum. Moreover, a specific, low-affinity GnRH binding protein (GnRH-BP) was found in the serum of the spotted dogfish. The binding of [125I]sGnRHA to the serum GnRH BP was dependent on incubation time, equilibrium being reached within 1 hr at 4 degrees; binding was rapid and completely reversible. Scatchard analysis yielded a linear plot with a Kd of 7.9 x 10(-7) M. The presence of a GnRH-BP in spotted dogfish serum suggests a probable action of GnRH via the general circulation. PMID- 7781964 TI - Diurnal variation in alpha-melanocyte-stimulating hormone content of various brain regions and plasma of the Texas toad, Bufo speciosus. AB - We measured the concentrations of alpha-melanocyte-stimulating hormone (alpha MSH) in various brain regions as well as in the pituitary gland and plasma of the toad Bufo speciosus during a 24-hr light:dark cycle. There was significant diurnal variation of alpha-MSH concentrations in the hypothalamus and brainstem. In both areas alpha-MSH concentrations were highest during the scotophase. Peak alpha-MSH concentrations in the hypothalamus were observed at 21.00 and 05.00 hr, while a single peak in alpha-MSH concentrations was observed in the brainstem at 21.00 hr. In contrast, peak alpha-MSH concentrations in the plasma were observed during the photophase at 17.00 hr, when brain concentrations of alpha-MSH were low. There was no significant diurnal variation observed in the pituitary content of alpha-MSH throughout the 24-hr light:dark cycle. These data suggest that different mechanisms control hypothalamic and pituitary alpha-MSH cells in the toad during the 24-hr light:dark cycle. The fact that peak alpha-MSH concentrations were observed in the hypothalamus during the activity period of the toad is consistent with the proposed role of alpha-MSH peptides in learning and memory processes. PMID- 7781965 TI - Evidence for functionally distinct subpopulations of steroidogenic cells in the domestic turkey (Meleagris gallopavo) adrenal gland. AB - A body of histological and functional evidence supports the hypothesis that there are functionally distinct subpopulations of steroidogenic cells comprising the avian adrenal gland. In the present study, we tested this hypothesis by evaluating the steroidogenic responses of density-dependent subpopulations of adrenal steroidogenic cells isolated from domestic turkeys fed either a high normal (control) sodium diet (0.4% Na+) or a Na(+)-restricted diet (0.04% Na+) for 8 days, the latter to stimulate the activity or appearance of possible zona glomerulosa-like cells. Subpopulations were visually yet reproducibly determined by their density-dependent separation on a continuous density gradient of Percoll (45%). The subpopulations were arbitrarily ascribed as being either low-density or high-density adrenal steroidogenic cells [LDAC (p = 1.0350-1.0585 g/ml) and HDAC (p = 1.0590-1.0720 g/ml), respectively]. LDAC and HDAC comprised 95.2 and 4.8%, respectively, of the total number of adrenal steroidogenic cells isolated. The LDAC was further subdivided into three visually distinct subpopulations. The functional differences between the LDAC subpopulations is discussed but was less dramatic than the functional distinction between the HDAC subpopulation and the pooled LDAC subpopulations. Basal aldosterone production values between control LDAC and HDAC were equivalent. In addition, there were no differences in maximal aldosterone production between control LDAC and HDAC in response to [Ile5]angiotensin II (AII), the avian equivalent, [Val5]AII, K+ (as KCl), and that supported by exogenous corticosterone. However, maximal aldosterone production in response to human ACTH-(1-39) (ACTH) of the LDAC was 32% greater than that of the HDAC. Na+ restriction enhanced basal aldosterone production of the LDAC by 84% over the control LDAC. In addition, it enhanced maximal aldosterone production of the LDAC in response to AII peptides, K+, ACTH and that supported by corticosterone by 54, 164, 83, and 74%, respectively, over that of the control LDAC. However, Na+ restriction disproportionately enhanced basal aldosterone production of the HDAC by 348% over that of the control HDAC. In addition, with Na+ restriction, maximal aldosterone production of the HDAC in response to AII, K+, and ACTH and that supported by exogenous corticosterone was consistently greater than that of the LDAC. Moreover, with Na+ restriction, maximal aldosterone production of the HDAC in response to AII peptides and K+ was increased over that of the control HDAC to a greater extent than was maximal aldosterone production in response to ACTH and that supported by corticosterone (% enhancement over control was as follows: AII peptides, 502%; K+, 668%; ACTH, 273%; corticosterone, 183%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7781966 TI - Melatonin rhythms in Atlantic salmon (Salmo salar) maintained under natural and out-of-phase photoperiods. AB - Diel changes in circulating melatonin were measured in juvenile Atlantic salmon, Salmo salar, maintained under natural and out-of-phase seasonal photocycles. Under natural daylengths of autumn, winter, spring, and summer circulating melatonin levels were inversely related to light intensity, with levels low during the day and high at night. The duration of the nocturnal increase in circulating melatonin was related to the duration of darkness, i.e., longer in winter than in summer. Under simulated seasonal photocycles circulating melatonin concentrations measured in August, October, and December were also elevated for the duration of darkness, irrespective of whether the photoperiods were synchronized or 6 months out-of-phase with the natural light and temperature cycles. Circulating melatonin also provided an accurate representation of the prevailing photoperiod in fish initially maintained on simulated natural photocycles, either synchronized or 6 months out-of-phase with the natural light cycle, and then held for 3 months on daylengths approximating the summer and winter solstices. Well-defined melatonin rhythms were always present, irrespective of time of year, photoperiod, and temperature. The amplitude of the nocturnal increase in circulating melatonin was similar in groups of fish maintained under simulated seasonal photoperiods 6 months out-of-phase with each other, but otherwise identical conditions, indicating that daylength per se did not influence the amplitude of the melatonin rhythm. The amplitude of the melatonin rhythm was slightly higher during the summer months, suggesting that temperature may modify circulating melatonin levels. These results demonstrate that circulating melatonin profiles always reflect the prevailing daylength and hence have the potential to provide the Atlantic salmon with accurate information on daily and calendar time, which could be utilised to time daily and seasonal events. PMID- 7781967 TI - Purification and structural characterization of vasoactive intestinal polypeptide from the trout and bowfin. AB - Vasoactive intestinal polypeptide (VIP) was purified from extracts of the stomachs of the rainbow trout, Oncorhynchus mykiss, and the bowfin, Amia calva. The primary structure of VIP from both species was the same: His-Ser-Asp-Ala-Ile Phe-Thr-Asp-Asn-Tyr10- Ser-Arg-Phe-Arg-Lys-Gln-Met-Ala-Val-Lys20-Lys-Tyr-Leu-Asn Ser-Val- Leu-Thr. This amino acid sequence shows only one amino acid substitution (Val5-->Ile) compared with the common sequence of VIP from the chicken, alligator, and European green frog. The structural identity of VIP from the trout and bowfin is consistent with the close phylogenetic relationship between the Salmoniformes and the Amiiformes and the data indicate that pressure to conserve the complete primary structure of VIP during vertebrate evolution has been very strong. PMID- 7781968 TI - Initial microbial adhesion is a determinant for the strength of biofilm adhesion. AB - This paper presents a hypothesis on the importance of initial microbial adhesion in the overall process of biofilm formation. The hypothesis is based on the realization that dynamic shear conditions exist in many environments, such as in the oral cavity, or on rocks and ship hulls. Recognizing that an entire biofilm is detached during high shear once the bond between the initially adhering organisms and a surface (often constituted through a so-called 'conditioning film') is broken, it becomes clear that research should focus on detachment rather than adhesion. Experiments were done in a parallel plate flow chamber in which attempts were made to detach adhering oral streptococci from glass by applying a high shear caused by the passage of a bubble, giving an air-liquid interface. Detachment of streptococci from bare glass and from an initially adhering actinomycete strain appeared not to occur. However, substantial detachment of adhering streptococci occurred when adhesion was mediated through a salivary conditioning film, presumably because of cohesive failure in the conditioning film. PMID- 7781969 TI - Induction and preliminary characterization of intracellular beta-glucosidases from a cellulolytic Streptomyces strain. AB - The cellulolytic actinomycete Streptomyces sp. QM-B814 possess an intracellular beta-glucosidase system which is induced by cellobiose and carboxymethylcellulose. Maximal beta-glucosidase activity was attained 8-10 h after inducer addition to exponential phase growing cultures. The induction is depressed in the presence of glucose. The system is composed of two electrophoretically different beta-glucosidases forms showing relative molecular masses of about 60 and 35 kDa, and pI values in the range 4.2-4.5. Both beta glucosidases are synthesized de novo. The enzymes share substrate preference and are both inhibited by delta-gluconolactone and p-chloromercuribenzoate. The induction pattern and glucose inhibition are similar for both enzymes. PMID- 7781970 TI - NtrBC-dependent expression from the Rhizobium meliloti dctA promoter in Escherichia coli. AB - Effects of the two-component sensor-regulator pairs DctBD and NtrBC upon the expression of a dctA::phoA fusion from Rhizobium meliloti were determined under excess and limiting nitrogen concentrations in Escherichia coli. Results indicated that NtrBC affected transcription from the dctA promoter on a number of regulatory levels and under different physiological conditions in the heterologous host. However, NtrBC-dependent cross-talk was not observed in free living R. meliloti under the conditions tested. Comparisons of the predicted amino acid sequences of DctD and NtrC from various sources indicated a specific region of the NtrC from rhizobia, which may have diverged from a consensus NtrC/DctD sequence to minimise interference between the two component systems, NtrBC and DctBD. PMID- 7781971 TI - Characterization of the superoxide dismutase gene and its upstream region from Methanobacterium thermoautotrophicum Marburg. AB - A gene (sod) encoding superoxide dismutase (SOD) was isolated from the strictly anaerobic archaeon Methanobacterium thermoautotrophicum Marburg. Its identify was confirmed by functional complementation of an Escherichia coli mutant strain lacking SOD activity and by DNA sequence analysis of a cloned fragment. Upstream of sod, separated by a 5-bp intergenic region, lies the open reading frame orfk which potentially codes for a protein of 209 amino acid residues. The amino acid sequence for this presumptive product had a similarity coefficient of 55.5% to a subunit of the alkyl hydroperoxide reductase (encoded by the ahpC gene) from Salmonella typhimurium. PMID- 7781972 TI - Construction and characterization of a Rhizobium leguminosarum biovar viciae strain designed to assess horizontal gene transfer in the environment. AB - An integration vector was developed which inserts cloned DNA in a non-essential site of the Rhizobium leguminosarum biovar viciae chromosome. The expression of integrated genes is under the control of the constitutive neomycin phosphotransferase II (nptII) promoter of transposon Tn5. The design of the vector ensures that loss of vector sequences can be detected, enabling selection of progeny containing only the requisite DNA. The newly constructed vector was employed to insert the Escherichia coli gusA gene conferring GUS activity into R. leguminosarum bv. viciae strain LRS39401 which is cured of its symbiotic plasmid (pSym). One GUS-positive transconjugant, strain CT0370, was shown to have lost all vector sequences. Conjugal transfer of pSym2004 (a Tn5-tagged derivative of symbiotic plasmid pRL1JI, which specifies pea nodulation and symbiotic nitrogen fixation) to CT0370, restored the GUS-positive strain's symbiotic proficiency. Strain CT0370 is presently being used in a field release experiment in order to assess the extent of pSym transfer in a natural R. leguminosarum bv. viciae population under environmental conditions. PMID- 7781973 TI - Cloning and sequencing of a novel hemolysis gene of Vibrio cholerae. AB - A hemolysis gene (hlx) which lyses sheep erythrocytes on blood agar plates when expressed in Escherichia coli was cloned from Vibrio cholerae. The cloned gene is predicted to encode a polypeptide of 92 amino acid residues with a deduced molecular mass of 10,451. E. coli transformed with this gene lysed sheep, goose, horse and chicken erythrocytes but not those of guinea pig and human. The hlx gene was observed in classical- and El Tor-biotype V. cholerae O1, V. cholerae non-O1, and V. mimicus, but not in V. parahaemolyticus. PMID- 7781974 TI - Glucosylation of cell wall proteins in regenerating spheroplasts of Candida albicans. AB - The cell wall of Candida albicans contains mannoproteins that are covalently associated with beta-1,6-glucan. When spheroplasts were allowed to regenerate a new cell wall, initially non-glucosylated cell wall proteins accumulated in the medium. While the spheroplasts became osmotically stable, beta-1,6-glucosylated proteins could be identified in their cell wall by SDS-extraction or beta-1,3 glucanase digestion. At later stages of regeneration, beta-1,3-glucosylated proteins were also found. Hence, incorporation of proteins into the cell wall is accompanied by extracellular coupling to beta-1,6-/beta-1,3-glucan. The SDS extractable glucosylated proteins probably represent degradation products of wall proteins rather than their precursors. Tunicamycin delayed, but did not prevent the formation of beta-1,6-glucosylated proteins, demonstrating that beta-1,6 glucan is not attached to N-glycosidic side-chains of wall proteins. PMID- 7781975 TI - Lack of lactate-proton symport activity in pck1 mutants of Saccharomyces cerevisiae. AB - Mutants of Saccharomyces cerevisiae without phosphoenolpyruvate carboxykinase activity showed no measurable lactate proton symport, while mutants without fructose-1,6-bisphosphatase had normal transport activity. Incubation of a pck1 mutant, under derepression conditions in the presence of glycerol, restored the activity of the lactate-proton symport, with identical kinetic characteristics to that in the wild-type. For efficient lactate-proton symport activity, not only is an external inducer such as lactic acid needed, but also a molecule derived from the acid metabolism may be necessary. PMID- 7781976 TI - Targeted disruption of the PD78 gene (traF) reduces pheromone-inducible conjugal transfer of the bacteriocin plasmid pPD1 in Enterococcus faecalis. AB - Bacterial sex pheromone, cPD1, induces sexual aggregation of Enterococcus faecalis harboring the bacteriocin plasmid, pPD1, and enables pPD1 to transfer at high frequency in a liquid culture. PD78 is a cPD1-inducible cell surface protein encoded by pPD1. The PD78 gene, traF, was disrupted by homologous recombination between pPD1 and an artificial vector having a deletion in the middle portion of traF. The disruption of traF did not affect the cPD1-inducible aggregation but reduced the transfer frequency of pPD1 to 2% of the wild-type level. PMID- 7781977 TI - NAD(+)-glycohydrolase productivity of haemolytic streptococci assayed by a simple fluorescent method and its relation to T serotype. AB - The ability of haemolytic streptococci to produce NAD(+)-glycohydrolase was investigated by a fluorescent assay. Enzyme production was found in 31 (91%) of 34 group A, 17 (61%) of 28 group C and eight (27%) of 30 group G isolates. The high producers were found in 22 (65%) of group A, one (4%) of group C and none of group G isolates. The high producers of the group A isolates belonged to T-1, T 3, T-4 or T-12 serotype. These results suggest that NAD(+)-glycohydrolase productivity of streptococci is closely related to specific Lancefield's groups or T serotypes. PMID- 7781978 TI - Transposon mutagenesis in halophilic eubacteria: conjugal transfer and insertion of transposon Tn5 and Tn1732 in Halomonas elongata. AB - Molecular genetic studies of halophilic eubacteria have been limited by the lack of a suitable method for mutagenesis. To overcome this, we established a transposon mutagenesis procedure for the ectoine-producing, halophilic bacterium Halomonas elongata. We used suicide plasmids pSUP101 and pSUP102-Gm to introduce the transposons Tn5 and Tn1732 respectively into H. elongata via Escherichia coli SM10 mediated conjugation. Our finding that H. elongata is sensitive to aminoglycoside antibiotics at low salinity enabled us to apply transposons that mediate kanamycin resistance. The insertions of transposon Tn1732 occurred at different sites in the chromosome of H. elongata, as proved by Southern hybridization analysis. Phenotypic analysis revealed that different auxotrophic and salt sensitive mutants were generated by mutagenesis with transposon Tn1732. To our knowledge this is the first report of a successful application of a transposon for direct generalized mutagenesis in a halophilic eubacterium. PMID- 7781979 TI - Lack of involvement of merT and merP in methylmercury transport in mercury resistant Pseudomonas K-62. AB - To clarify whether the merT and merP genes play a role in the transport of methylmercury, we constructed a deletion plasmid, pMRD141 which lacked the genes conferring the organomercurial lyase and the mercuric reductase from plasmid, pMRA17 containing the entire broad-spectrum mercury resistance determinants of the 26 kb-plasmid from Pseudomonas K-62. Plasmid, pMRD141 showed hypersensitivity to Hg2+ but still expressed a normal sensitivity to methylmercury. The mercury induced hypersensitive cells carrying pMRD141 took up appreciably more 203Hg2+ than the induced resistant cells with pMRA17 and the sensitive cells with cloning vector, Bluescript II SK(+) but no difference in the uptake of CH3(203)Hg2+ among these three strains was found. These results suggested that the merT and merP are only involved in the Hg2+ transport but do not participate in the transport of methylmercury. PMID- 7781980 TI - Plasmid and chromosomal DNA recovery by electroextraction of cyanobacteria. AB - High voltage electroporation has been investigated as a method for rapid recovery of plasmid and chromosomal DNA from the cyanobacteria Nostoc PCC 7121, Synechococcus PCC 7002, and Anabaena PCC 7120. Pulses of 18 kV/cm and higher applied to concentrated Nostoc cells carrying a shuttle plasmid (pRL25) resulted in copious release of nucleic acids and phycobiliproteins into the suspending medium. Small portions of these supernatants, when electroporated with Escherichia coli, gave rise to hundreds of E. coli transformants which contained pRL25. Electroporation of Synechococcus carrying plasmid pAQE19 did not cause detectable release of macromolecules but did reveal a low-level, voltage independent 'leakage' of pAQE19 into the medium. Electroextraction of Nostoc or Anabaena followed by addition of E. coli and delivery of a second high-voltage pulse permitted direct, one-cuvette transfer of shuttle plasmids from these cyanobacteria into E. coli. Electroextraction of single cyanobacterial colonies, as shown for Nostoc, also released sufficient chromosomal DNA for amplification of specific sequences by the polymerase chain reaction. PMID- 7781981 TI - Mycoplasma gallisepticum 16S rRNA genes. AB - The genome of Mycoplasma gallisepticum A5969 contains a truncated pseudogene for 16S rRNA in addition to a single unsplit rRNA-operon and a second discontinuous set of rRNA genes. Other M. gallisepticum strains tested do not possess the truncated gene. This gene is almost identical to full-size isolated 16S rRNA gene starting from at least 500 nucleotides upstream of the coding sequence and ending at the 977th nucleotide within the structural part of 16S rRNA. PMID- 7781983 TI - Pore-forming bacteriocins of gram-positive bacteria and self-protection mechanisms of producer organisms. AB - Proteinaceous antimicrobial compounds are produced by a diversity of species ranging from bacteria to humans. This review focuses on the mode of action of pore-forming bacteriocins produced by Gram-positive bacteria. The mechanism of action of specific immunity proteins, which protect the producer strains from the lethal action of their own products (producer self-protection), are also discussed. PMID- 7781982 TI - Sucrose-derived exopolymers have site-dependent roles in Streptococcus mutans promoted dental decay. AB - We have constructed a panel of mutants of S. mutans V403 which are defective in one or more of the glucosyltransferase genes (gtfB, C or D) or the fructosyltransferase gene (ftf). These strains have been tested for virulence in a gnotobiotic rat caries model with reference to both buccal (smooth surface) and sulcal (pit and fissure) carious lesions. Our data suggest differing roles for degradable and non-degradable polymers at buccal and sulcal sites. Non-degradable polymers (made by products of the gtfB and C genes) contributed significantly to the severity of smooth surface lesions. However, our studies suggested their role in pit and fissure lesions was not as important as the role of degradable polymers. Specifically, a mutant deficient in the major insoluble glucan synthesizing activity (product of the gtfB gene) was 25% more cariogenic on sulcal surfaces than was the wild-type V403 strain. We propose that extracellular glucosyltransferases and fructosyltransferase compete for sucrose and that this competition influences pathogenicity at differing tooth sites. PMID- 7781985 TI - A novel dodecadepsipeptide, cereulide, is an emetic toxin of Bacillus cereus. AB - A vacuole-formation substance, cereulide of Bacillus cereus, is an emetic toxin in animals. Both oral administration and intraperitoneal injection of cereulide caused dose-dependent emesis in Suncus murinus, a new animal model of emesis. Vagotomy or a 5-HT3 receptor antagonist completely abolished this emetic effect. Therefore, cereulide causes emesis through the 5-HT3 receptor and stimulation of the vagus afferent. We also found that our purified cereulide caused swelling of mitochondria of HEp-2 cells. PMID- 7781984 TI - Intrinsic insensitivity to cadmium of the L-lactate oxidizing system in staphylococcoccus aureus. AB - Starved cells of cadmium-sensitive Staphylococcus aureus 17810S accumulated 109Cd via the Mn2+ porter energized by the membrane potential (delta psi) generated by L-lactate oxidation. However, Cd2+ accumulation did not result in inhibition of respiration and consequent generation of electrochemical proton gradient (delta muH+) via the respiratory chain. Thus, delta muH(+)-consuming processes, such as ATP synthesis and [14C]glutamate transport proceeded normally, despite the presence of Cd2+ in the cytoplasm. The mechanism of the intrinsic cadmium insensitivity of the L-lactate oxidizing system is discussed. PMID- 7781987 TI - Assignment of genes to Leishmania infantum chromosomes: karyotype and ploidy. AB - The use of various pulsed-field electrophoresis methodologies under different conditions allowed us to determine the Leishmania infantum karyotype. A total of 25 chromosomal bands ranging in size from 375 to 3300 kb were resolved amounting to a minimum genomic DNA mass of about 2.6 x 10(7) pb. By molecular hybridization and on the basis of the karyotype, specific gene sequences could be assigned to particular chromosomes. A bias in the chromosomal distribution of different markers was found since 9 out of the 12 analysed gene markers hybridize with chromosomal bands XIXa and XIXb. We infer that chromosomal bands XIXa and XIXb, differing in about 30 kb, could be representing a pair of homologous chromosomes and that another pair of homologs may be also defined by chromosomal bands XVII and XVIII. PMID- 7781986 TI - Sequence of cDNA coding for a 65 kDa adhesive protein for the specific detection of Trichomonas vaginalis by PCR. AB - A Trichomonas vaginalis cDNA library was constructed and recombinant plaques were screened using rabbit immunoglobulins specific for P65, a protozoan protein involved in pathogenicity that we identified in a previous study. A 1.38 kilobases cDNA fragment coding for the P65 protein was cloned in E. coli and then sequenced. On the basis of of the sequence obtained, six primers were synthesised and used to set up a Polymerase Chain Reaction. The presence of a specific amplicon in all 30 clinical isolates tested shows that P65 is a conserved and stable gene. The reaction is highly sensitive (as few as 5 to 10 parasites can be detected) and specific for Trichomonas vaginalis; the gene coding P65 adhesin can be therefore considered a very good molecular target for polymerase chain reaction-based diagnostic purposes. PMID- 7781988 TI - Kinetics of substrate oxidation by whole cells and cell membranes of Helicobacter pylori. AB - Oxygen uptake by Helicobacter pylori cells and membranes was determined. Cells from stirred broth cultures or agar plates, suspended in buffer, possessed a variable and apparently endogenous respiration which could be sustained for several hours. In contrast, oxygen consumption by cells from statically incubated broth cultures, in the absence of added substrate, was transient or undetectable. These latter cells, however, oxidised ethanol, fumarate, glucose, D-lactate, pyruvate and succinate, though glucose-oxidising ability declined rapidly. The Kms for D-lactate, pyruvate and succinate metabolism were low (< or = 20 microM) and oxygen uptake was approximately 1.5, 2 and 2 mol per mol substrate respectively, indicating metabolism beyond acetate plus CO2 and implying the presence of tricarboxylic acid cycle activity. Cell membranes oxidised fumarate, D-lactate, NADH, NADPH and succinate. NADPH oxidation was six times more rapid than that of NADH. Rates of oxygen uptake by cells suspended in buffer with metabolisable substrate were < 20% of those for cells suspended in a brain heart infusion medium. Uninoculated medium consumed significant quantities of oxygen. PMID- 7781990 TI - Luminometry and PCR-based monitoring of gene-tagged cyanobacteria in Baltic Sea microcosms. AB - The cyanobacterium Synechocystis 6803 was tagged by chromosomal integration of the firefly luciferase gene, luc, resulting in the modified strain Synechocystis 6803-luc. The tagged cells were monitored in Baltic Sea microcosms both by detection of the luc gene by PCR amplification and by measurement of luc gene expression (bioluminescence) in total protein extracted from sediment and water. A new method was developed for isolation and concentration of total protein from sediment for optimization of luciferase quantitation. The detection limit for Synechocystis with a chromosomal luc insertion by bioluminescence was in the order of 4 x 10(3) cells per g sediment, a considerable improvement in sensitivity over previous methods. Another improvement was to use an internal luciferase standard to correct for quenching of light output by impurities in the samples. Baltic sea microcosms were inoculated with Synechocystis 6803-luc, and the luc DNA and luciferase protein specific to the tagged cells were monitored over time. A decrease in luminescence in the microcosm water was observed, simultaneously with an increase in luminescence in the sediment, suggesting settling of the luc-tagged cells in the sediment layer. PMID- 7781989 TI - Isolation and characterization of a bacterium which utilizes polyester polyurethane as a sole carbon and nitrogen source. AB - Various soil samples were screened for the presence of microorganisms which have the ability to degrade polyurethane compounds. Two strains with good polyurethane degrading activity were isolated. The more active strain was tentatively identified as Comamonas acidovorans. This strain could utilize polyester-type polyurethanes but not the polyether-type polyurethanes as sole carbon and nitrogen sources. Adipic acid and diethylene glycol were probably the main degradation products when polyurethane was supplied as a sole carbon and nitrogen source. When ammonium nitrate was used as nitrogen source, only diethylene glycol was detected after growth on polyurethane. PMID- 7781991 TI - Carbon dioxide regulated secretion of the EaeB protein of enteropathogenic Escherichia coli. AB - An eaeA mutant (intimin deficient) of enteropathogenic Escherichia coli stimulated phosphorylation of several host cell proteins, showing that intimate adherence is not required to activate signal transduction pathways in enteropathogenic E. coli-infected cells. Growth of enteropathogenic E. coli in tissue culture medium in 5% CO2, in the presence or absence of cultured cells, resulted in the secretion of several bacterial proteins. Two of these, 36 kDa and 20 kDa in size, were expressed at significantly lower levels in air. N-terminal sequencing and analysis of secreted proteins of an eaeB mutant indicated that the 36 kDa secreted protein was EaeB, previously implicated in the stimulation of signalling pathways in enteropathogenic E. coli-infected cells. PMID- 7781992 TI - Phylogenetic analysis by 16S ribosomal DNA sequence comparison reveals two unrelated groups of species within the genus Ruminococcus. AB - Phylogenetic analysis of the genus Ruminococcus based on 16S rDNA sequence data showed the genus to be phylogenetically heterogenous. Ruminococcus species fall within the radiation of the Bacillus/Clostridium subphylum of the Gram-positive line of descent. Two distinct and unrelated clusters are recovered. One group contains R. flavefaciens, R. albus, R. bromii, and R. callidus. The second group constitutes R. gnavus, R. hansenii, R. lactaris, R. obeum, R. productus and R. torques which together with some Clostridium species may constitute a new genus. PMID- 7781993 TI - Cloning and characterization of a gene from Pasteurella haemolytica A1 involved in lipopolysaccharide biosynthesis. AB - A Pasteurella haemolytica A1 gene involved in the biosynthesis of a moiety on the core of the lipopolysaccharide molecule has been cloned and characterized. Escherichia coli clones which carry this gene showed an alteration of its lipopolysaccharide migration profile on tricine SDS-PAGE and exhibited resistance to the core-specific phage U3. In addition, lipopolysaccharide extracted from the E. coli clones was recognized by an anti-corespecific antiserum, but not by antiserum specific for the O antigen of P. haemolytica A1 lipopolysaccharide. Nucleotide sequence analysis of the cloned DNA identified an open reading frame (lpsA) coding for a protein of 263 amino acids which showed significant homology with a Haemophilus influenzae type b lipooligosaccharide biosynthesis gene. PCR amplification of genomic DNA, using primers based on the P. haemolytica A1 lpsA sequence, yielded products from only the A biotypes of P. haemolytica. PMID- 7781994 TI - Intragenic suppression of a luxR mutation: characterization of an autoinducer independent LuxR. AB - The Vibrio fischeri luminescence genes are activated by the LuxR protein and a diffusible signal termed the autoinducer. LuxR consists of two domains, a C terminal transcriptional activator domain, and an N-terminal autoinducer-binding domain, which serves to regulate the function of the C-terminal domain. We have isolated and characterized an intragenic suppressor of a mutation that maps to the N-terminal domain and blocks autoinducer binding. The suppressor changes an alanine residue at position-221 in the C-terminal domain to a valine. In Escherichia coli, the suppressor allows partial activation of the V. fischeri luminescence genes although E. coli containing this protein remains unable to bind autoinducer. To further analyze the influence of the second-site mutation on luxR function, we constructed a luxR gene that coded for a protein with a wild type N-terminal domain and with the ala-221 to val substitution in the C-terminal domain. This protein activated the luminescence genes in the presence or absence of autoinducer, and it bound autoinducer at levels comparable to the wild-type LuxR protein. Apparently, the alanine to valine substitution at position-221 allows activity of the C-terminal domain in a fashion independent of whether autoinducer is bound to the N-terminal domain. PMID- 7781995 TI - Linkage analysis of the gene encoding precursor protein of diapause hormone and pheromone biosynthesis-activating neuropeptide in the silkmoth, Bombyx mori. AB - We have determined the map position of the gene encoding a common precursor protein for diapause hormone and pheromone biosynthesis-activating neuropeptide (the DH-PBAN gene, Dh) in the silkmoth, Bombyx mori. First we compared the structure of introns in the DH-PBAN gene by the polymerase chain reaction, and found that the Dh locus carried three alleles, DhA1, DhA2 and DhB. The DhA1 and DhA2 alleles contained a fourth intron consisting of 740 bp, whereas DhB had a longer fourth intron of 770 bp. DhA1 and DhA2 contained a fifth intron consisting of 940 bp, whereas the fifth intron in DhB was much longer and consisted of 1700 bp. DhA1 was distinguished from DhA2 by an RFLP in the fifth intron after digestion with Rsa I. Linkage analyses using these polymorphisms showed that Dh was linked to the bp gene on chromosome 11, and independent of markers on chromosomes 1, 2, 3, 4, 5, 6, 7 and 13. To determine the map position, we obtained F1 hybrids between the n501 strain (K DhA1) and the w30 strain (+K DhB), and backcrossed the F1 hybrid to females of the w30 strain. From the segregation of K and Dh in 864 individuals in the next generation, the recombination value was calculated as 25.5% between K and Dh. Similarly we obtained backcross progeny between the No. 744 strain (Bu DhA1) and the w30 strain (+Bu DhB), and calculated the recombination value between Bu and Dh as 30.4% from 487 progeny.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7781996 TI - Accumulation of mutations affecting body weight in inbred mouse lines. AB - The variation from spontaneous mutations for 6-week body weight in the mouse was estimated by selection from a cross of two inbred sublines, C57BL/6 and C57BL/10, separated about 50 years previously from the same inbred line. Selection was practised high and low for 12 generations from the F2, followed by one generation of relaxation. The lines diverged by approximately 1.7 g or 0.7 sd. The additive genetic variance was estimated in the F2 by restricted maximum likelihood and from the selection response, and from this variance the mutational heritability hM2 was estimated using the number of generations since divergence. Estimates of hM2 range from 0.08 to 0.10% depending on the method of analysis. These estimates are similar to those found for other species, but lower than other estimates for the mouse. It is concluded that substantial natural and, perhaps, artificial selection operated during the maintenance of the sublines. PMID- 7781997 TI - Survey of genomic repeat sequence-PCRs that detect differences between inbred mouse strains. AB - We have developed molecular markers that distinguish between several inbred and congenic mouse strains using polymerase chain reaction (PCR) amplification of genomic DNA repeat sequences. Mouse genomic DNA, digested with four base recognition site-restriction endonucleases, was amplified by PCR using primers for the following repeat sequences: B1 (Alu homolog), LINE, LLR3, IAP, human Alu and myoglobin. Amplification products analysed by agarose gel electrophoresis and stained with ethidium bromide produced unique DNA fragments, some of which are specific for each of 12 strains tested. This method can be used for molecular analysis of the mouse genome, including genetic monitoring. PMID- 7781998 TI - Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. AB - Seven imprinted genes are currently known in the mouse but none have been identified yet in the distal imprinting region of mouse Chromosome (Chr) 2, a region which shows striking linkage conservation with human chromosome 20q13. Both maternal duplication/paternal deficiency and its reciprocal for distal Chr 2 lead to mice with abnormal body shapes and behavioural abnormalities. We have tested a number of candidate genes, that are either likely or known to lie within the distal imprinting region, for monoallelic expression. These included 3 genes (Cebpb, E2f1 and Tcf4) that express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to neurological and probably behavioural problems, and 3 genes (Cd40, Plcg1 and Rcad) that are less obvious candidates but sequence information was available for designing primers to test their expression. On/off expression of each gene was tested by reverse transcription-polymerase chain reaction (RT-PCR) analysis of RNA extracted from tissues of mice with maternal duplication/paternal deficiency and its reciprocal for the distal region of Chr 2. None of the 13 genes is monoallelically expressed in the appropriate tissues before and shortly after birth which suggests that these genes are not imprinted later in development. This study has narrowed down the search for imprinted genes, and valuable information on which genes have been tested for on/off expression is provided. Since there is considerable evidence of conservation of imprinting between mouse and human, we would predict that the 13 genes are not imprinted in human. Five of the genes: E2f1, Tcf4, Kcnb1, Cd40 and Rcad, have not yet been mapped in human. However, because of the striking linkage conservation observed between mouse Chr 2 and human chromosome 20, we would expect these genes to map on human chromosome 20q13. PMID- 7781999 TI - Comparative population structuring of molecular and allozyme variation of Drosophila melanogaster Adh between Europe, west Africa and east Africa. AB - Restriction enzyme molecular variation in Drosophila melanogaster Adh was compared between three natural populations from Europe, West Africa and East Africa. The frequency distribution of silent variation in the slow allele was compatible with the neutral model in all three samples. The number of haplotypes in East Africa was significantly higher than in the other two populations. The largest divergence, as measured by Fst, was between the East African population and a group made up from the West African, the European, and previously studied American populations. We suggest that a split first occurred within African populations at least 44000 years ago. European populations separated from West Africa more recently, between the last glacial maximum and the post-glacial optimum, 18,000 to 8,000 years ago. We suggest that this species was domesticated recently relative to human evolution, possibly with the advent of agriculture. Population differentiation with respect to the two allozymes, fast and slow, does not follow the geographical pattern of silent variation. It opposes European to both African populations, and probably results from selection for adaptation to alcohol in recent temperate populations. PMID- 7782000 TI - Suicide risk in frail elderly people relocated to nursing homes. PMID- 7782001 TI - Relocation stress syndrome: a comprehensive plan for long-term care admissions. PMID- 7782002 TI - The resident: the heart of it. PMID- 7782003 TI - A profile of Pennsylvania nurse's aides. PMID- 7782004 TI - Carotid endarterectomy in elderly vascular patients: experience in a community hospital. PMID- 7782005 TI - Staffing and managing special care units for Alzheimer's patients. PMID- 7782007 TI - Another look at napping in older adults. PMID- 7782006 TI - Research utilization: meeting the challenge. PMID- 7782008 TI - Community partnerships: home health care for elderly minorities. PMID- 7782009 TI - Digestive dilemmas. PMID- 7782010 TI - Decisions about behavior-modifying medications for people with dementia. PMID- 7782011 TI - Professional issues and public concerns. PMID- 7782012 TI - Structure, occurrence, biosynthesis, biological activity, synthesis, and chemistry of aromadendrane sesquiterpenoids. PMID- 7782013 TI - The chemistry of melanins and melanogenesis. PMID- 7782015 TI - [Responsibilities and value of autopsy. Determining death--1]. PMID- 7782014 TI - [Breast carcinoma--revision of after-care recommendations. 1: Results of many large studies from the literature are in agreement]. AB - In the past, recommendations for the follow-up of women who had undergone primary treatment for local or locoregional breast cancer, were mostly concerned with "programmed" protocols in which the frequency of the follow-up appointments, and the examinations to be performed on the respective occasions (e.g. bone scintigraphy, chest X-ray, abdominal ultrasound, mammography and laboratory investigations) were rigidly fixed. Numerous new facts reported in the literature (including prospective randomized studies and meta-analyses) now appear to show that this formalized approach to follow-up brings the patient no advantage in terms of approved chances of being cured, longer survival or better quality of life. For this reason, for breast cancer follow-up, a strategy is proposed that is based on meticulous history-taking and clinical examination, and which also emphasizes psychosocial rehabilitation aspects. Examinations using technical equipment are carried out only when justified by clinical suspicion of recurrent disease. PMID- 7782016 TI - [Procedure for autopsy. 1: Responsibilities in autopsy--determining death]. PMID- 7782017 TI - [Preventing imminent amputation by regional hyperthermic fibrinolytic drug perfusion. An intraoperative procedure for reopening thrombosed arteries in extremities]. PMID- 7782018 TI - [Long-term therapy with a retard theophylline preparation]. AB - The present study was conducted to investigate the therapeutic effect of long term treatment with a slow-release theophylline preparation on the pulmonary functions FEV1 and peak exspiratory flow (PEF). A total of 908 patients took part in this open multicenter study. Treatment with the slow-release theophylline resulted in an increase of FEV1 and PEF of about 20% in asthma and between 11% and 14% in COPD. Apart from theophylline itself, the galenic nature of the slow release formulation also contributed to the therapeutic effect. PMID- 7782019 TI - [The atypical neuroleptic clozapine (Leponex)--current knowledge and recent clinical aspects]. AB - The dibenzoepine derivative clozapine is seen as a prototype of an atypical neuroleptic, because clozapine has good antipsychotic efficacy but only minimal dopamine antagonistic properties in common animal paradigms. The latter is reflected by the observation that extrapyramidal symptoms during clozapine are a rare phenomenon. Furthermore, recent studies in the USA demonstrated a superior efficacy of clozapine in schizophrenic patients who are nonresponsive to classic neuroleptics. Therefore, the introduction of clozapine in the USA was performed in 1990 despite the well-known risk of agranulocytosis (1-2% during the first year of treatment); however, under restricted conditions regarding the mandatory weekly control of the white blood cell count. For the use of clozapine in Europe, it should be underlined that in 1992 the indication was restricted to "acute and chronic forms of schizophrenia" whereas formerly it was permitted to treat several other neuroleptic resistant syndromes with clozapine, e.g. severe psychotic excitement, aggressive behavior or manic or atypical psychosis. The usage of clozapine in these indications is now only permitted under the restricted legal conditions of a "therapeutic trial" in selected patients. However, several indications for which clozapine has been used successfully in Europe are currently re-investigated in the USA, hopefully leading to a redefinition and extension of the indication spectrum. On the other hand, the American multicenter trials lead to the conclusion that the treatment with clozapine is not furthermore the treatment of last choice but a serious therapeutic alternative which should be available for all schizophrenic patient in case of neuroleptic resistance or of severe side effects of standard neuroleptics. Clozapine treatment leads to an improvement of the quality of life in one third of these schizophrenics and, moreover, results in a marked reduction of costs mainly by reducing the rehospitalisation rates. On the other hand, the list of well-known side effects of clozapine (e.g. agranulocytosis, increased risk of seizures, initial sedation) has to be extended (e.g. transient leucocytosis or eosinophilia, rare but severe complications like cardiorespiratory arrest and "sudden death" during combination with benzodiazepines, case reports of pericarditis, pancreatitis or polyserositis). On the background of possible cardiorespiratory complications we recommend to start the first treatment with clozapine in high risk patients (e.g. those in older age or in case of organic brain impairment) only in restricted indications and only in centers with sufficient clozapine experience. PMID- 7782020 TI - [Disorders of autonomic regulation in Parkinson syndrome]. AB - Ever since the first description of Parkinson's disease, it has not only been associated with the classical triad of akinesia, rigor and tremor but also with autonomic regulation disorders. However, the studies published on this subject show differing and partly contradictory results. A large number of studies demonstrate a distinct autonomic disorder. On the other hand there are authors who question an affliction of the autonomic nervous system and others who attribute the autonomic disorder to Parkinson specific medication. To make matters worse, the various pathogeneses of Parkinson's syndrome within the patients collectives have not been sufficiently differentiated and nomenclature of the multisystem degeneration was handled in different ways. Taking our examinations of the various autonomic functions and the underlying literature into critical consideration, we come to the conclusion that regulation disorders of the cardiovascular system, gastrointestinal and urinary tract, as well as sweat and thermoregulation are often seen in the idiopathic Parkinson's disease. In our opinion the idiopathic Parkinson's syndrome must be attributed to the multisystem degenerations. Autonomic dysfunction occurs in different intensities in the disease. PMID- 7782021 TI - [Friedrich Holderlin's psychosis from the viewpoint of Karl Leonhard]. PMID- 7782022 TI - [Parasitological research projects of Chagas disease in Paraguay]. PMID- 7782024 TI - Hemodialysis patient regarded as a primary hyperoxaluria after long-term hemodialysis and renal transplantation. AB - Primary hyperoxaluria (PH) is a rare inborn error of oxalate metabolism resulted in autosomal recessive genetic defects. Clinical manifestations and end stage renal failure are developed during childhood in most cases, but occasionally they begin later in life. The diagnosis of PH is quite difficult due to diminished oxalate excretion after the renal function was declined. especially after initiation of hemodialysis therapy. We report here an adult case who was introduced into hemodialysis and subsequently regarded to have primary hyperoxaluria (PH). In clinical situations, this case had some peculiar clinical signs such as histories of frequent stone formations, impressive dental manifestations and destructive erosions of bones resembling renal osteodystrophy. There might be more PH patients among hemodialysis patients. PH should be considered in hemodialysis patients whenever curious bone changes and/or dental manifestations with history of frequent urolithiasis are recognized in the earlier course of hemodialysis therapy. PMID- 7782023 TI - A preliminary study of retreatment of chronic hepatitis C with interferon. AB - Nine patients with chronic hepatitis C virus (HCV) infection and no complete response to the first treatment with natural interferon (IFN)-alpha, were prescribed a second treatment with IFN. Five patients (Group A) with unsustained levels serum alanine aminotransferase (ALT) after the first treatment were administrated the same species of IFN but in a higher dose. The remaining four patients (Group B), with no normalization of ALT throughout the observation period of the first treatment, were administrated IFN-beta. HCV RNA was eliminated in three patients of group A and in two of group B patients during 6 months follow up and ALT reverted to normal levels. These results suggest that retreatment with a higher dose of the same species of IFN-alpha can be effective in case of a relapse and that IFN-beta can be effective for those not responding to IFN-alpha. PMID- 7782025 TI - [Survey of using conditions of sterilized and non-sterilized disinfectants in Kyushu University Hospital]. AB - We surveyed the using conditions of sterilized and non-sterilized disinfectants in Kyushu University Hospital by questionnaires and direct hearing. The kinds and concentrations of disinfectants used were generally proper for their respective purposes. However, there were also some inappropriate cases, such as the cleansing of mucosal membranes with chlorhexidine (Hibitane) gluconate and uses of the concentrations different from those described in the package insert. The present survey was very useful for proper uses of disinfectants. PMID- 7782026 TI - Hepatic resection under in situ hemihepatic hypothermic perfusion with hepatoprotective agents. AB - Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field. PMID- 7782027 TI - Changes in IL-6 and IL-8 after hepatectomy in patients with liver cirrhosis. AB - Changes in tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were investigated before and after hepatectomy in patients with or without liver cirrhosis (5 cases without liver cirrhosis and 14 cases with liver cirrhosis). Both the IL-6 and IL 8 values of the cirrhotic patients were significantly higher on the first postoperative day (POD) as compared with the non-cirrhotic patients. Overall, no significant correlation was found between peak values of IL-6 or IL-8 and blood loss or operating time. In the case of the cirrhotic patients, correlation of both IL-6 and IL-8 with operating time was significant at p < 0.05, gamma = 0.534 and 0.586, respectively. No correlation was found between blood loss and the peak value of IL-6, but significant correlation (gamma = 0.647, p < 0.05) was found between them in cirrhotic patients. There was no consistent increase in TNF-alpha and IL-1 beta following hepatectomy. These findings indicate that procedures undertaken to reduce the excessive production of these cytokines may be useful for preventing complications after hepatectomy in cirrhotic patients. PMID- 7782028 TI - The interaction between hepatic arterial and portal venous blood flows; simultaneous measurement by transit time ultrasonic volume flowmetry. AB - Intra-operative measurement of the afferent circulation of the liver, namely hepatic artery and portal venous flow was carried out in 14 anesthetized patients with carcinoma of the splanchnic area, mainly in the head of the pancreas, by means of transit time ultrasonic volume flowmetry. The hepatic artery flow, portal venous flow and total hepatic flow were 0.377 +/- 0.10; 0.614 +/- 0.21; 0.992 +/- 0.2761/min, respectively. The ratio of hepatic arterial flow to portal venous flow was 0.66 +/- 0.259. There was a sharp, significant increase in hepatic arterial flow (29.8 +/- 6.1%, p < 0.01) after the temporary occlusion of portal vein, while the temporary occlusion of the hepatic artery did not have any significant effect on portal venous circulation. The interaction between hepatic arterial flow and portal venous flow is much in dispute, but, as the data presented here show, there is no doubt that the decrease in portal venous flow immediately gives rise to a significant increase in hepatic artery circulation. PMID- 7782029 TI - Circulating enzyme activities of collagen turnover and undulin in patients with various degrees of schistosomiasis and alcoholic liver cirrhosis. AB - In contrast to alcoholic liver disease, schistosomiasis leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Since conventional liver function tests and liver biopsy provide little information about the dynamics of the fibrotic process, we measured the activities of two circulating enzymes of collagen turnover, namely serum galactosylhydroxylysyl glucosyl-transferase and plasma prolidase activity, together with undulin, a novel extracellular matrix glycoprotein. The study encompassed 15 healthy control subjects. 69 patients with various stages of Schistosoma mansoni/hematobium infection [28 with early active infection and no organ involvement, 27 with hepatosplenic involvement, and 14 with complications of portal hypertension] and 16 patients with alcoholic liver cirrhosis. Liver biopsies were obtained from 30 schistosomal patients for histopathological grading. Serum galactosylhydroxylysyl glucosyl-transferase was significantly increased in all clinical stages of schistosomiasis (p < 0.05), but normal in alcoholic cirrhosis. In contrast, plasma prolidase activity showed a significant increase only in early schistosomiasis (p < 0.01), but dropped to subnormal levels in advanced stages (p < 0.001). Undulin was highly elevated both in alcoholic patients and in all schistosomal groups (p < 0.001), and was capable of distinguishing between early and advanced schistosomal stages. We conclude that serum undulin may be a valuable non-invasive parameter for monitoring the course of schistosomal and alcoholic liver disease. PMID- 7782030 TI - Clinical significance of antiphospholipid antibodies in fulminant hepatic failure. AB - We examined the incidence of antiphospholipid antibodies (APA) in patients with fulminant hepatic failure (FHF) and various liver diseases using the enzyme linked immunosorbent assay (ELISA), and assessed possible correlations with the pathophysiology of these diseases. The APA assay employed cardiolipin (CL), phosphatidylserine (PS), and phosphatidylinositol (PI) as antigens. Anti-CL IgA antibody was detected in 13/14 (92.9%) patients with FHF. The incidence of anti CL-IgG, anti-CL-IgM, anti-PS-IgG, and anti-PI-IgG was 14.3%, 35.7%, 64.3%, and 71.4%, respectively. Despite the high incidence of APA in FHF, these antibodies were not detected in most patients with acute or chronic hepatitis. There was a negative correlation between anti-CL-IgA and the platelet count, and a negative correlation between anti-PI-IgG and the amount of residual liver parenchyma. Our results suggest that APA develop secondarily to hepatocyte or sinusoidal cell damage and may aggravate both thrombocytopenia and liver failure. PMID- 7782032 TI - Lymph node metastasis and surgical management of gastric cancer invading the esophagus. AB - In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy. PMID- 7782033 TI - Changes in wound healing factors in liver cirrhosis after esophageal transection for esophageal varices. AB - Quantitative changes in plasma wound healing factors in cirrhotic patients after esophageal transection were evaluated and compared with those of non-cirrhotic esophageal cancer patients (controls) after esophageal resection. Serum total protein, albumin and fibronectin were maintained at the same levels as those in controls when multiple units of fresh frozen plasma and albumin products were employed. Nevertheless, the principle protease inhibitors including alpha-1 antitrypsin and alpha-1-acid-glycoprotein showed little increase by the 3rd postoperative day, while those of controls increased as much as twofold at this time. Levels of complements C3 and C4 showed consistent depression, with little change during the study period. We conclude that the levels of some of the plasma proteins essential in wound healing are depressed in cirrhotic patients during the critical period after surgery. PMID- 7782031 TI - Recombinant a2 interferon (a-IFN) with chemo-hormonal therapy in patients with hepatocellular carcinoma (HCC). AB - Recent studies on HCC treatment reveal a tendency to use combined immuno-chemo therapy. Additionally, new agents have been suggested in this field. We therefore studied 7 patients with proven inoperable HCC who were treated in accordance with the following protocol, and 5 untreated patients used as controls. Therapeutic trial: 1) 1FNa (Roferon): 6 MU x 7 days consecutively every 3 weeks, 2) Adriamycin (doxorubicin): 60 mg/m2 i. v. once every 3 weeks (500 mg total dose), 3) Tamoxifen: 10 mg p.o. twice daily continuously 4) Desferrioxamine (DFO): 500 mg i.m. daily x 7 days consecutively every 3 weeks, 5) ascorbic acid: 300 mg p.o. daily 1 hour after DFO administration x 7 days consecutively every 3 weeks. Follow-up studies were performed monthly and comprised clinical, biochemical, radiological and immunological (T-cell subsets, NK cells, monocyte-macrophage function, IL-2r expression, HLA-DR expression) parameters. Compared with the control group, the treated group had a longer survival rate (p < 0.001), increased tumor regression and less progressive disease. Immunologically, the treated patients with the maintenance of a sufficient immune status were associated with a prolonged survival rate. No serious side effects of the regimen were observed. In conclusion, IFNa combined with chemohormonal therapy appears to be beneficial in HCC patients. In addition, a prolonged survival rate might correlate with the maintenance of an adequate immune status in the patients. PMID- 7782034 TI - Hepatopancreatoduodenectomy for squamous and adenosquamous carcinoma of the gallbladder. AB - The characteristics of squamous or adenosquamous cell carcinoma of the gallbladder differ quite markedly from those of adenocarcinoma, although the incidence is extremely low. Recently, we encountered both of the former types of gallbladder carcinoma: a 77-year-old man with squamous cell carcinoma and a 70 year-old man with adenosquamous cell carcinoma of the gallbladder. Both had a large mass in the gallbladder fossa region with infiltration to the liver and invasion of the duodenum. Hepatopancreatoduodenectomy was performed on both of these patients. The TNM stage of the former was IV (T4N0M0) and of the latter IV (T4N0M0) and of the latter IV (T4N1bM0). The former has remained well without recurrence for about 1 year and 4 months after the operation, while the latter died of recurrent disease 6 months after operation. The true reason for the difference in the prognosis of these two patients was not known. However, hepatopancreatoduodenectomy is considered to be a most adaptable operative procedure for squamous or adenosquamous cell carcinoma of the gallbladder in view of their mode of spread, and the presence of lymph node metastasis might be a factor of poor prognosis. PMID- 7782035 TI - Significance of intraoperative measurement of liver consistency prior to hepatic resection. AB - The functional reserve of the liver should be estimated prior to hepatectomy. While the experienced liver surgeon often relies on the findings of manual palpation intra-operatively, this approach remains a subjective one. In 22 of our patients scheduled for hepatectomy, we measured intra-operatively hepatic consistency as well as the parameters of liver function. Hepatic consistency is augmented during progression from non-fibrosis to cirrhosis. We found a statistically significant correlation between liver consistency and the indocyanine green retention rate at 15 minutes (r = 0.682; p = 0.0009) and portal vein pressure (r = 0.733; p = 0.0008). Prothrombin time, the hepaplastin test, total bilirubin and glutamic pyruvic transaminase showed no significant correlation with hepatic consistency. The safety limits of the hepatic blood circulation for the performance of hepatectomy can be estimated using parameters of consistency in this organ. PMID- 7782036 TI - Ultrasound-guided percutaneous transhepatic gallbladder drainage followed by laparoscopic cholecystectomy: a new trial in the treatment of severe acute suppurative cholecystitis. AB - Seven cases of acute suppurative cholecystitis underwent percutaneous transhepatic gallbladder drainage followed by laparoscopic cholecystectomy at the Tainan Municipal Hospital. All the patients had frank septic phenomena clinically, including fever, jaundice, leukocytosis and unstable blood pressure. Organisms were cultured from both blood and bile specimens. Ultrasound-guided transhepatic puncture of the gallbladder was performed for bile drainage, and laparoscopic cholecystectomy was subsequently performed two to five days later after the patients had stabilized. No procedure-related complications from either percutaneous transhepatic gallbladder drainage or laparoscopic cholecystectomy were observed. All patients had early recovery, shortened hospital stay and good cosmetic results. These preliminary results show that laparoscopic cholecystectomy is a safe method and can be employed in those patients with symptomatic gallstone associated with suppurative cholecystitis after preoperative biliary drainage. PMID- 7782037 TI - Exocrine pancreatic function after recovery from necrotizing pancreatitis. AB - The aim of the present study was to investigate the exocrine pancreatic function after recovery from necrotizing pancreatitis. The exocrine function was analysed in 53 patients who had recovered from their first attack of necrotizing pancreatitis. In a group of 23 patients (Group A), three follow-up studies were performed between four weeks and 12 months after recovery from acute pancreatitis. A second group of 30 patients (Group B) was submitted to only one function test 18 months after recovery from acute necrotizing pancreatitis. Exocrine pancreatic function was observed after endogenous stimulation using the Lundh test meal. In Group A, after four weeks 74% of the patients had mild-to moderate insufficiency, while 26% suffered from severe impairment of pancreatic function. Twelve months after recovery, only 16% of the patients showed a normal pancreatic response, while 84% still had pancreatic insufficiency of variable severity. In Group B, 13% of the patients showed a normal pancreatic response, while mild-to-moderate insufficiency was observed in 81%. Severe pancreatic insufficiency was measured only in 6% of these patients. After recovery from necrotizing pancreatitis persistent global or dissociated functional insufficiency is found in 80-85% of the cases. Individual pancreatic enzyme secretion varies quiet considerably during the course of recovery in the follow up period. PMID- 7782038 TI - Duodenal variceal bleeding--successfully treated by mesocaval shunt after failure of sclerotherapy. AB - A 68-year-old male patient with liver cirrhosis and bilateral diffuse hepatoma presented with massive upper gastrointestinal bleeding caused by rupture of duodenal varices. Surgery had to be performed after sclerotherapy failed to stop the bleeding. A mesocaval shunt with graft interposition controlled the hemorrhage. Follow-up endoscopic examination showed complete disappearance of the varices. After surgery, the patient had two episodes of mild hepatic encephalopathy, which easily responded to treatment. There was no rebleeding, and he died of hepatic malignancy ten months after the shunt procedure. PMID- 7782039 TI - Multiparametric evaluation of functional outcome after pylorus-preserving duodenopancreatectomy. AB - The aim of the present study was to evaluate the clinical, morphological and functional results obtained in a group of patients previously submitted to Traverso-Longmire pylorus-preserving duodeno-pancreatectomy (PPDP). The study was performed as a clinical, endoscopic, radioisotopic and electro-manometric evaluation. An analysis of the results allowed us to conclude that: 1) most patients show good clinical features, and this becomes more evident as post operative time progresses; 2) bile reflux gastritis is an infrequent event; 3) gastric emptying times in patients overlap those seen in control subjects, and progressive normalization occurs postoperatively. The best clinical results coexist with normal gastric emptying times; 4) gastrojejunal interdigestive motor activity shows a reduction in phase 3 and a relative increase in phase 2. We argue that the motor activity of the upper gastrointestinal tract can restore, from a functional point of view, the new anatomical situation. On the basis of the good clinical and functional results, pyloric preservation seems to be the most physiological procedure for the restoration of alimentary continuity following duodenopancreatic resection. PMID- 7782040 TI - Liver involvement and its course in patients operated on for ulcerative colitis. AB - The prevalence of associated liver involvement in 214 patients with ulcerative colitis undergoing definitive surgery was evaluated, with special emphasis on the subsequent course of liver changes. At the time of colectomy or proctocolectomy 45 patients (21%) had more than transient liver involvement, and 13 (6.1%) fulfilled the criteria of primary sclerosing cholangitis (PSC). Of the other 32 patients with minor liver involvement four had steatosis, one chronic active hepatitis, one viral A hepatitis, and 14 possibly early sclerosing cholangitis or unspecific reactive hepatitis. During a mean follow-up of nine years, four patients with PSC (31%) showed clinical progression, but none of those with minor histological changes or those with no liver disease at surgery did so. Alkaline phosphatase levels showed a decreasing tendency, and minor histological changes improved after surgery, while repeated cholangiography mostly demonstrated progression or a static state. The results indicate that asymptomatic sclerosing cholangitis in association with ulcerative colitis is not always a progressive disease, and proctocolectomy may have a beneficial effect on the long-term course of sclerosing cholangitis in its early phase. PMID- 7782041 TI - The influence of age on the management of anal cancer. AB - The standard treatment for anal cancer is combination chemo-radiotherapy. Management decisions such as radical chemotherapy, resective surgery for poor response or relapse are frequently modified by age-associated comorbid factors. Between 1980 and 1990, our regional cancer center serving a population of 1.8 million saw 78 patients with squamous carcinoma of the anus. We have compared patients who were younger than 65 years (n = 38) with those older than 65 years (n = 38). The mean +/- standard deviation age for the whole cohort was 65 +/- 12 years, with a ratio of 2 females to each male presenting. Fewer of the elderly age group had major surgery (26% vs. 42%) (p = 0.03), and fewer suffered no toxicity (42% vs. 26%) (p = 0.03). However, 61% of the under-65-year age group are alive disease-free vs. 26% of the elderly group (p = 0.03). Similarly, only 18% of the under-65-year group died with disease compared with 37% of the elderly group (b = 0.03). For the series as a whole, the crude mortality was 42%, with 27% dying of their disease. The stage distribution, and the amount of radiotherapy or chemotherapy administered was not age-specific, but younger patients had more surgery and suffered more toxicity, with a greater proportion remaining alive and disease-free, and fewer dying of their disease. These data suggest that a more aggressive multi-modality approach in the elderly may improve disease response and survival. PMID- 7782042 TI - Spontaneous perforation of the left hepatic duct--a case report. AB - We report on a patient with spontaneous perforation of the left hepatic duct who presented with abdominal pain, jaundice and fever. The correct diagnosis was not established until extravasation of contrast medium from the left hepatic duct, as demonstrated by the cholangiogram, was observed. The patient developed two bile stained intraperitoneal encapsulated fluid collections, which were diagnosed by ultrasonography, and high bilirubin levels in the fluid aspirated from the encapsulations, which were also found at operation. Closure of the perforation with sutures, decortication of the encapsulations and choledocholithotomy for stone extraction with T-tube insertion were performed. Recovery was complete at follow-up examinations. PMID- 7782043 TI - Subulcerous fibrin gluing represents a further effective endoscopic therapy for the treatment of bleeding ulcer. PMID- 7782044 TI - Recurrence near the resection line of hepatocellular carcinoma in the anterosuperior subsegment of the liver--the effect of the argon beam coagulator. AB - The present paper examines the relationship between the patterns of intrahepatic recurrence after resections of hepatocellular carcinoma and surgical margins in cases located in the anterosuperior subsegment of the liver. In 95 curative resections of the liver for hepatocellular carcinomas less than 5 cm in size, 29 tumors were located in the anterosuperior subsegment of the liver. The recurrence rates of tumors in the anterosuperior subsegment and other regions were 16/29 (55.2%) and 39/66 (59.1%), respectively. Recurrences near the resection line were significantly more common in the anterosuperior subsegment (6/29) than in other regions (2/66) of the liver (P < 0.05). The surgical margin from the tumor edge to the resection line was significantly shorter in tumors of the anterosuperior subsegment (4.6 +/- 9.7 mm) than in those of other regions (9.7 +/- 10.6 mm) (P < 0.01). The effect of an argon beam tissue coagulator was also examined in rat livers. Exposure to an argon beam tissue coagulator for 10, 30 and 60 seconds at a power setting of 100 watts was capable of burning out tissue to a depth of 6.0, 10.5 and 13.3 mm from the resection line of the rat liver, respectively. An exposure of 10 seconds is thought to be sufficient to destroy any microscopic residues of malignant cells near the resection line. Thus, an argon tissue coagulator could potentially be of value for the prophylaxis of recurrence near the resected surface. PMID- 7782045 TI - Bone mineral density in children and adolescents with juvenile diabetes: selective measurement of bone mineral density of trabecular and cortical bone using peripheral quantitative computed tomography. AB - Bone mineral density (BMD) was studied in 21 children and adolescents with type I diabetes and in age- and sex-matched healthy controls. BMD was selectively measured in trabecular and total bone using peripheral quantitative computed tomography (pQCT). Cortical bone density was calculated. There was a decrease of trabecular bone density (-18.9%, p < 0.01), total bone density (-9.0%, NS) and cortical bone density (-5.1%, NS) in diabetes. Trabecular bone density was inversely correlated with the duration of diabetes and the concentration of glycosylated hemoglobin (HbA1) (r = -0.48, p = 0.027 and r = -0.63, p = 0.002, respectively). Total BMD correlated inversely with HbA1 (r = -0.52, p = 0.017). pQCT allows the selective measurement of metabolically active trabecular bone where changes of mineralization first occur. We conclude that pQCT is a useful method for investigating BMD in diabetes. PMID- 7782046 TI - Alcohol inhibits 11-beta-hydroxysteroid dehydrogenase activity in rat kidney and liver. AB - Male Wistar rats were treated with different ethanol concentrations diluted in drinking water in order to evaluate the effect of acute ethanol intoxication on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity in liver and kidney tissue homogenates. Rats with the highest ethanol consumption (15% ethanol supplementation) showed a significant decrease in both hepatic and renal 11 beta OHSD activity as compared to the control group (p < 0.005). In the same group, aldosterone plasma levels were significantly lower than in controls (p < 0.01), while corticosterone (B) plasma levels were slightly higher, suggesting that the increase in intrarenal B concentrations, probably related to the acute ethanol consumption, might be responsible for a nonspecific B mineralocorticoid activity. PMID- 7782047 TI - Age-related changes in plasma corticosterone and aldosterone responses to exogenous ACTH in the rat. AB - Age related changes in the time courses of response of plasma corticosterone and aldosterone to exogenously applied ACTH were simultaneously studied in old (female and male) Long-Evans rats and compared to both young and adult pentobarbitone-anesthetized and dexamethasone-pretreated control rats. Acute intravenous injection of either 0.5 or 50.0 ng ACTH (1-24)/100 g body weight increased plasma concentrations of the two steroids with a similar time course in all groups of rats. However, we observed a significant age-related attenuation in the plasma corticosteroid response. Thus, in old as compared to young rats there was a decrease of approximately 45, 40 and 30% in plasma corticosterone levels respectively 8 min after the lower dose of ACTH in female and 45 min after the higher dose in female and male rats. Similarly, an attenuated (approximately 38%) response of plasma aldosterone levels, induced 45 min after the higher dose of ACTH, was observed both in old female and male rats. These results suggest that the previously reported age-related decreases of in vivo corticosterone and aldosterone secretion are, at least in part, due to a reduced capacity of adrenocortical cells for steroid biosynthesis and release in response to stimulation by ACTH. PMID- 7782048 TI - Efficacy of growth hormone replacement therapy in children with organic growth hormone deficiency after cranial irradiation. AB - We evaluated the growth response of 20 childhood cancer survivors who received growth hormone (GH) replacement therapy (0.3 mg/kg/week) for at least 12 months. In all subjects, GH deficiency was associated with cranial irradiation and was documented with growth charts, bone age, and somatomedin C levels; at least one GH stimulation test was available for 14 children. Pretreatment overall growth velocity was 3.3 +/- 0.5 cm/year (mean +/- SE) over a 3-year period. After GH replacement, growth velocity was 8.6 +/- 0.6 cm/year during the first year (n = 20), 7.2 +/- 0.5 cm/year during the second year (n = 17), 5.9 +/- 0.6 cm/year during the third year (n = 11), and (6.1 +/- 0.6 cm/year during the fourth year (n = 7). Growth response, tabulated by age at onset of GH replacement, was compared with the response in GH-naive children with idiopathic GH deficiency (data obtained through the Genentech Inc. National Cooperative Growth Study Summary, September 1991); the growth velocity fell within the range described for idiopathic GH deficiency adjusted for either chronological or bone age. We conclude that children with GH deficiency after cranial irradiation for neoplastic diseases respond to GH replacement therapy as well as children with idiopathic GH deficiency. PMID- 7782049 TI - Enhanced nocturnal melatonin secretion in women with functional secondary amenorrhea: relationship to opioid system and endogenous estrogen levels. AB - The purpose of this study was to evaluate the role of the opioid system and the estrogen environment in the nocturnal secretion of melatonin in women with secondary amenorrhea (SA). Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (p < 0.01 vs. women with normal menstrual cycles). There were significant negative correlations between cumulative melatonin levels (between 8 p.m. and 8 a.m.) and serum estradiol-17 beta (r = -0.561, p < 0.01) and between peak serum melatonin values and serum estradiol-17 beta concentrations (r = -0.608, p < 0.01) in SA. Intravenous administration of a conjugated estrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (p < 0.05), but a continuous intravenous infusion of naloxone (1.6 mg/h from 8 p.m. to 6 a.m.), an opiate antagonist, did not affect nocturnal melatonin secretion in SA. Our findings suggest that elevated nocturnal melatonin secretion may be related to low estrogen levels, but that it is not mediated by the opioid system. PMID- 7782050 TI - Auditory brainstem responses in thyroid diseases before and after therapy. AB - The aim of this study was to evaluate through the auditory brainstem responses (ABRs) the electrical events generated along the auditory pathway in 56 adult patients affected with hyper- and hypothyroidism. Twenty-four normal-hearing hyperthyroid patients affected with Graves' disease and 32 normal-hearing hypothyroid patients (9 with subclinical and 23 with overt hypothyroidism) were subjected to standard (clicks at 21 pps) and sensitized ABR with masking wide band (masking noise). In addition, thyroid scintiscan and ultrasonography, free T3 and T4, total T3 and T4, TSH, antimicrosomal and antithyroglobulin antibodies, audiogram and impedance tests were performed in all the patients. This study was repeated after 6-12 months of treatment in conditions of euthyroidism. The results showed changes of ABRs both in the standard procedure as well as in the sensitized test in 6 hyperthyroid (25%) and 8 hypothyroid patients (25%). All the patients with abnormal ABRs had overt hypothyroidism (8/23; 34.7%). The ABRs became normal in 5 out of 6 Graves' patients after 6-12 months of methimazole treatment. ABRs remained abnormal in all the hypothyroid patients despite their having been on L-thyroxine treatment for 6-12 months and were euthyroid for at least 5 months before the study was repeated. These findings suggest that ABR abnormalities are indicative only of a nonspecific injury in the bulbo-ponto mesencephalic centers. Alterations of ABRs in thyroid diseases are not specific in relation to hyper- or hypothyroidism. Lastly, there is a relationship between ABR abnormalities and the degree of hypothyroidism, even if ABR alterations are not always reversible after long-term therapy. PMID- 7782051 TI - Low serum levels of tumor necrosis factor-alpha in insulin-dependent diabetic children. AB - We measured serum levels of tumor necrosis factor-alpha (TNF-alpha) in 48 children with insulin-dependent diabetes mellitus (IDDM), divided into two groups according to disease duration (group I < 6 months and group II > 3 years): group I 15 patients, aged 2.2-13.7 years, and group II 33 patients, aged 4.5-25.5 years. Thirty-six age- and sex-matched healthy subjects served as controls. TNF alpha levels were measured by immunoradiometric assay. We found that TNF-alpha levels were lower in all IDDM patients (29.65 +/- 3.83 pg/ml) than in controls (74.74 +/- 10.17 pg/ml) (p < 0.0001), as well as in group I (24.07 +/- 3.65 pg/ml) and group II (32.16 +/- 5.29 pg/ml) as compared to controls (p < 0.001). TNF-alpha levels were significantly lower in patients with antibodies than in those without antibodies and in controls. Similar results were found in longstanding IDDM patients. No correlation was found between serum TNF-alpha and chronologic age, duration of disease, metabolic control, insulin requirement and HLA typing. During a 1-year follow-up study in 12 group I patients no significant variations in TNF-alpha levels were observed. It has been reported that the administration of exogenous TNF suppresses the development of diabetes in nonobese diabetic mice, low producers of endogenous TNF. The results suggest that aberrant TNF-alpha synthesis may contribute to immune dysregulation thus favoring the development of autoimmune diseases. PMID- 7782052 TI - Alternation of hypo- and hypercalcemia in a parathyroidectomized patient with breast cancer. AB - We report the case of a 54-year-old female patient with postoperative hypoparathyroidism. Despite the fact that she was receiving calcitriol replacement therapy, following the appearance of bone metastases due to breast cancer she developed severe crises of hypo- and hypercalcemia. PMID- 7782053 TI - Hormonal, genetic and clinical findings in an XX male. AB - A 17-year-old XX male with constitutional delay of growth and development and genetic short stature is described. Testosterone levels were normal but luteinizing-hormone-releasing-hormone-stimulated gonadotropin concentrations were increased. Testicular biopsy showed atrophic tubuli seminiferi and hyperplasia of the Leydig cells, and the spermiogram indicated azoospermia. Molecular analysis demonstrated the SRY gene close to the centromere of the paternally derived X chromosome. Clinical data in addition to the cytogenetic and molecular aspects are discussed. PMID- 7782054 TI - Gonadotrophin control of follicular function. AB - It has been known for over 50 years that both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are required to stimulate both follicular development and oestradiol synthesis. However, previous experiments employing FSH and LH preparations (whether of pituitary or urinary origin) have not been able to answer unequivocally, whether an observed response was solely due to either FSH or LH because they were not pure preparations. In view of the recent availability of both 100% pure recombinant human FSH and recombinant human LH, we now have a unique opportunity to test their contribution in the regulation of ovarian function. Such experiments may have important clinical implications as they offer a means to interpret the effect of 'pure' FSH preparations when used to stimulate ovarian function in women undergoing different therapeutic regimens. To test the contribution of LH to optimize ovarian responsiveness to FSH, 21-day old hypophysectomized, immature, female rats were treated for a 2-day period with varying total doses of rec-FSH (30-72 IU and/or rec-LH at 12-hourly intervals. At 48 h after the first injection, ovaries were removed, weighed and used to isolate granulosa and thecal interstitial cells for assessment of basal and gonadotrophin responsive steroidogenesis in vitro; homogenized to extract total RNA for Northern analysis of 17-hydroxylase/C17-20-lyase (cytochrome P-450C17); mRMA; or examined using in situ hybridization to determine the expression of P-450C17 in the rat graafian follicle. The experiments demonstrated the potential for rec-FSH to influence LH-responsive androgen synthesis (via a paracrine mechanism) which involves an up-regulation of thecal P-450C17 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782055 TI - Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization: results of a meta-analysis. AB - The observation of adverse effects of high-follicular-phase LH levels on fertilization, cleavage, embryo quality and pregnancy suggests that exogenous LH administration for ovarian stimulation in IVF may also be detrimental. The purpose of this study was to compare the use of FSH with hMG in IVF by conducting a systematic overview and meta-analysis of the evidence in the literature from randomized trials comparing the two gonadotropins. The data were extracted and pooled from eight studies that satisfied the inclusion criteria. The results show that FSH performs significantly better than hMG and is associated with at least 50% higher clinical pregnancy rates. PMID- 7782056 TI - Experience using preparations of follicle-stimulating hormone alone to stimulate the ovaries for assisted conception after pituitary desensitisation and simplified management of treatment. AB - The results are reported of 2,204 cycles of treatment started for in vitro fertilisation and embryo transfer or gamete intrafallopian transfer, during 5 years, 1990-1994, using only follicle-stimulating hormone (FSH) preparations to stimulate the ovaries following pituitary desensitisation, combined with greatly simplified scheduling and monitoring of treatment. The physiological principles underlying these choices are discussed. In all women under 40 years of age and men with normal sperm, the use of unpurified urinary FSH in 1990-1993 resulted in oocyte collection in 94% of cycles started, pregnancy in 29% and live births in 23%. Using highly purified urinary FSH (uFSH-HP; Metrodin HP) during 1994, the rate for oocyte collection was 97% and pregnancy 25% (birth rates not yet available). The difference compared with previous years was not significant. A study of 93 first cycles using uFSH-HP showed that the dosage required was usually (expressed as medians) 24 ampoules over 12 days (2 ampoules/day) resulting in 9 oocytes (range 2-36) of which 93% were mature and 64% resulted in cleaving embryos. The results are comparable with the best using human menopausal gonadotropin or unpurified FSH and classical detailed monitoring. PMID- 7782057 TI - Results from in vitro fertilization and intracytoplasmic sperm injection with purified gonadotrophins (Metrodin HP). AB - Purified urinary follicle-stimulating hormone (uFSH-HP; Metrodin HP, Serono Ltd.) was compared with a combination of pure FSH and human menopausal gonadotrophin (hMG; Pergonal, Serono Ltd.) in patients undergoing standard in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In standard IVF, pure FSH gave a significantly higher pregnancy rate per started cycle than did the combination with hMG (35 vs. 18%, p < 0.05). No differences between standard IVF and ICSI were seen which could be associated with hormonal stimulation in an open non-randomized series of patients. In 11 ICSI cycles, the use of recombinant FSH (Gonal F, Serono Ltd.) resulted in 4 ongoing pregnancies. PMID- 7782058 TI - The role of conditioned taste aversion in the hypophagia induced by intraperitoneal epinephrine and glucose. AB - It has been repeatedly shown that relatively high doses of epinephrine (E) and glucose (G) injected intraperitoneally (ip) produce hypophagia in fasted rats. In the present work we used a conditioned taste aversion (CTA) paradigm in order to test whether this effect could be due to "malaise." We determined the effect on food intake and saccharin preference with the following treatments: (a) E ip 100 and 250 micrograms/kg; (b) E ip 250 micrograms/kg with or without previous alpha 1 plus beta adrenergic blockade; (c) G ip 3.5 and 4 g/kg. Both doses of E significantly reduced food intake more than 75% but only the high dose produced a significant (50%) reduction in saccharin preference. Blockade of alpha 1 and beta adrenergic receptors completely suppressed the E-induced hypophagia but attenuated only slightly the taste aversivon effect. Both doses of G decreased food intake but only the high dose reduced saccharin preference; part of these effects would appear to be due to the high osmolarity of the solution. The present results indicate that E and G may induce CTA in our experimental conditions. However, their hypophagic and aversive effects seem to be elicited by different mechanisms. PMID- 7782059 TI - Gonadal hormone levels and spatial learning performance in the Morris water maze in male and female meadow voles, Microtus pennsylvanicus. AB - The present study examined the relationships between spatial learning and circulating levels of plasma estradiol and testosterone in adult male and female meadow vole, Microtus pennsylvanicus. Meadow voles are induced ovulators and most females that are housed with females or in isolation are in constant diestrus, whereas most females that are housed with males are in constant behavioral estrus. In this study sexually mature, adult male and female meadow voles housed with either females (constant diestrus) or males (constant behavioral estrus) were required to learn the spatial position of a hidden, submerged platform in the Morris water maze. Individual voles were tested using two blocks of four trials twice a day for 3 days for a total of six blocks. Task retention was examined with a probe trial 1 day after the last acquisition trial. Females were divided into two groups based on the median level of plasma estradiol [High Estradiol (15.79 +/- 1.20 pg/ml) and Low Estradiol (6.22 +/- 2.79 pg/ml) Females]. Males were similarly divided on the basis of median plasma testosterone levels [High (2.53 +/- 0.96 ng/ml) and Low Testosterone (0.45 +/- 0.08 ng/ml) Males]. High Estradiol females exhibited significantly longer latencies to reach the hidden platform, indicating poorer acquisition, than did either males (P = 0.025) or Low Estradiol females (for Blocks, 2, 3, 4, and 6, P = 0.037). Male superiority in spatial learning performance was evident only when High Estradiol females were compared to males. There were no significant performance differences between High and Low Testosterone males. There were also no group differences in retention, with all voles displaying significant retention of the spatial task. There was, however, a significant correlation between plasma estradiol levels in females and retention, with higher estradiol levels being associated with poorer retention. These results suggest that levels of estradiol in adult female meadow voles are significantly related to spatial learning, with low levels of estradiol being associated with better spatial learning. There was no evidence that levels of testosterone were related to spatial performance in adult male meadow voles. The results suggest that estradiol may have activational effects on spatial learning in the adult meadow vole and that sex differences in spatial learning are evident only when High Estradiol females are compared to adult males. PMID- 7782060 TI - Hormonal correlates of breeding status, nest construction, and parental care in multiple-brooded northern mockingbirds, Mimus polyglottos. AB - Blood samples were taken from free-living male and female mockingbirds to determine correlations between plasma steroids and breeding behavior. Plasma levels of testosterone (T), estradiol (E2), progesterone (P), and corticosterone (B) were assessed during pre-breeding courtship, while males built nests, while females incubated, while parents fed young, and while males built new nests as pairs continued to care for dependent fledglings. Samples were also taken from unmated males holding spring territories. In males, T and P fluctuated with breeding phase, and in all groups, male T levels exceeded basal values measured in autumn. But, when mated males built nests in the absence of young, T levels were higher than in all other conditions, though only for early broods. In females too, T and P levels changed with breeding phase; T levels rose during courtship and while males built first nests and were intermediate during nest construction for later broods. Male and female P levels rose during courtship and when males built nests with young present. While feeding young in the nest, males showed significantly higher corticosterone levels than females, though in females, both P and B levels increased during incubation for replacement broods. These findings strengthen an earlier finding that T may activate male nest construction, and they suggest that breeding behavior may be related to T in females as well. Progesterone data raise the possibility that P too, may be linked to breeding behavior in male and female mockingbirds. Sex differences in corticosterone levels during the nestling period may reveal subtle costs associated with male mockingbirds' highly aggressive defense against predators. PMID- 7782061 TI - A comparison of LH secretion and brain estradiol receptors in heterosexual and homosexual rams and female sheep. AB - This study examined endocrine components of sexual orientation of male sheep. Sexual orientation of adult rams was identified through standardized sexual performance tests. Four rams that copulated with ewes, four rams that never mounted females and copulated with males, and eight ewes were used in the experiments. Exogenous estradiol benzoate (50 micrograms, i.m.) stimulated (P < .05) a preovulatory-like LH surge 16-22 hr after administration to females. Estradiol did not (P > .05) affect LH release of heterosexual or homosexual rams. Thirty days after the estradiol challenge, sheep were euthanized and areas of the amygdala (AMY), hypothalamus (HYP), anterior pituitary (AP), and preoptic area (POA) of the hypothalamus were collected. Occupied and unoccupied content of estradiol receptors (ER) was determined. The content of ER in the amygdala of both homosexual rams and ewes was similar, but less than (P < .05) the content of ER in heterosexual rams. The ER content measured in other brain regions did not differ by sex or orientation. In summary, results from these data show that the preovulatory LH surge mechanism that is a characteristic of the female does not occur in either homosexual or heterosexual rams. Conversely, the ER content of the AMY of homosexual rams is similar to that of ewes and differs from the heterosexual male. Differences in ER content between heterosexual and homosexual rams imply that the amygdala serves as a link for input from potential mates. These data suggest that the amygdala not only plays a role in sexual behavior but may be involved in sexual orientation of rams. PMID- 7782062 TI - Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats. AB - Our recent demonstration of receptors for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) in rat brain with the highest density within the hippocampus and dentate gyrus suggests novel functional roles for gonadotropic hormones within the brain. The present study investigated whether 125I-hCG can cross the blood-brain barrier and reach hippocampus and the possible role of hCG in the regulation of several behavioral activities associated with the hippocampal formation in the rat. About 1/100th of peripherally injected 125I-hCG crossed the blood-brain barrier in an intact form and was found in cerebrospinal fluid and in hippocampus. Intraperitoneal (IP) or intracerebroventricular (ICV) injections of highly purified hCG on the morning of proestrus of cycling female rats resulted in changes in several hippocampus-associated behaviors. hCG-treated animals were generally less active and showed less exploratory behavior as compared to saline-injected control animals. There was no difference, however, in latency to enter the open field between hCG-treated and control animals. Taste neophobia was dramatically decreased following IP as well as ICV injection of hCG. No differences were found in the memory component of T-maze performance; however, the hCG-treated rats exhibited decreased stereotypic behavior. In summary, hCG can cross the blood-brain barrier, and peripheral or central administration of hCG affects several hippocampus-associated behaviors suggesting that hippocampal LH/hCG receptors are most likely involved in mediating these effects. Some of the observed behavioral changes have parallels in pregnant women. PMID- 7782063 TI - Oxytocin changes in males over the reproductive cycle in the monogamous, biparental California mouse, Peromyscus californicus. AB - Levels of plasma oxytocin in male Peromyscus californicus were assessed across the reproductive cycle to provide a foundation for subsequent studies of the hormonal basis of paternal behavior and pair bonds. In Experiment 1, plasma oxytocin levels were significantly higher in expectant fathers than in virgin males or fathers. Plasma oxytocin increased in expectant fathers 1 day postcopulation and remained elevated for the first 15 days of gestation. Plasma oxytocin declined by Day 20 of gestation and oxytocin levels remained low in fathers throughout the lactational period. Oxytocin levels among expectant fathers did not differ between parental and nonparental males or between infanticidal and noninfanticidal males, suggesting that plasma oxytocin may not be involved in the prepartum onset of paternal behavior or the inhibition of infanticide. In Experiment 2, plasma oxytocin levels also did not differ between males that were parental or non-parental prepartum or postpartum. However, males separated from their mate and pups on the day of birth had elevated oxytocin levels on Day 3 postpartum compared to males that remained with their family, suggesting that disruption of the pair bond and/or absence of the young affects plasma oxytocin levels in males. This possibility remains to be determined. PMID- 7782064 TI - Central angiotensin II induces thirst-related responses in an amphibian. AB - Angiotensin II (A-II), a potent inducer of thirst-related behavior in many vertebrate species, was injected into the third ventricle of the brain of the spadefoot toad, Scaphiopus couchii. Following injection of 10 ng A-II the animals demonstrated a significant increase in water absorption response (WR) behavior, in which toads press their ventral skin to a moist surface and absorb water by osmosis. This increase in the frequency of WR behavior was positively correlated with an increase in water gain during a 2-hr period indicating that centrally injected A-II stimulates water intake by this amphibian species. We have previously demonstrated that WR behavior is also induced by intraperitoneal (i.p.) injections of A-II in several anuran species, including S. couchii. Thus, amphibians, like other vertebrates, demonstrate an increase in water intake in response to either centrally administered or circulating A-II. A second series of experiments was conducted to determine whether the above response to A-II might be secondary to increases in the circulating levels of aldosterone (ALDO) or antidiuretic hormone because the release of both of these hormones has been shown by others to be stimulated by A-II. Scaphiopus couchii injected i.p. with either ALDO or arginine vasotocin in dosages of 1, 10, and 100 micrograms/100 g body weight showed no increase in WR behavior relative to toads injected with saline alone. These results suggest that A-II acts directly on the brain of S. couchii to induce WR behavior. PMID- 7782065 TI - Hormonal responses to aggression vary in different types of agonistic encounters in male tree lizards, Urosaurus ornatus. AB - Hormonal responses to male-male interactions have been detected in some studies of vertebrates but not others. One hypothesis that may partially explain these discrepancies is that differences in the duration of male-male interactions cause different hormonal responses. In social systems based on dominance-subordinance hierarchies interactions often last longer than if exclusive territories are maintained. Tests of the hypothesis that encounter duration explains discrepancies in hormonal responses would be facilitated by a species that shows elements of both types of social systems, such as species in which males practice alternative reproductive tactics. We compared plasma levels of corticosterone and testosterone in males of the territorial morph of the tree lizard (Urosaurus ornatus) subjected either to short (15 min) male-male encounters or to long (7 days) dominance interactions. In the long interactions, dominant males had lower levels of corticosterone than did subordinate males over the first day, but this difference subsequently disappeared. In sharp contrast, winners of short-term encounters had elevated plasma corticosterone levels which peaked the day after the encounter. Thus, males isolated after a short encounter experienced an increase in corticosterone that was apparently inhibited in males who continued interacting with other males. The delayed increase in corticosterone after a short encounter may facilitate metabolic recovery from the encounter, mobilize metabolic substrates useful in subsequent encounters, or may alter subsequent behavior. The response does not appear to be simply recovery from exercise because in a second experiment males exercised for 15 min did not show a similar delayed increase in corticosterone the following day. Testosterone levels were also monitored and did not change in any of these treatments. These results demonstrate that the duration and the outcome of male-male interactions may each independently influence hormone levels. PMID- 7782066 TI - Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma. AB - Mutations in the human PAX3 gene have previously been associated with two distinct diseases, Waardenburg syndrome and alveolar rhabdomyosarcoma. In this report we establish that the normal human PAX3 gene is encoded by 8 exons. Intron exon boundary sequences were obtained for PAX3 exons 5, 6, 7, and 8 and together with previous work provide the complete genomic sequence organization for PAX3. Difficulties in obtaining overlapping genomic clone coverage of PAX3 were circumvented in part by RARE cleavage mapping, which showed that the entire PAX3 gene spans 100 kb of chromosome 2. Sequence analysis of the last intron of PAX3, which contains the previously mapped t(2;13)(q35;q14) translocation breakpoints of alveolar rhabdomyosarcoma, revealed the presence of a pair of inverted Alu repeats and a pair of inverted (GT)n-rich microsatellite repeats within a 5-kb region. This work establishes the complete structure of PAX3 and will permit high resolution analyses of this locus for mutations associated with Waardenburg syndrome, alveolar rhabdomyosarcoma, and other phenotypes for which PAX3 may be a candidate locus. PMID- 7782067 TI - The human archain gene, ARCN1, has highly conserved homologs in rice and Drosophila. AB - A novel human gene, ARCN1, has been identified in chromosome band 11q23.3. It maps approximately 50 kb telomeric to MLL, a gene that is disrupted in a number of leukemia-associated translocation chromosomes. cDNA clones representing ARCN1 hybridize to 4-kb mRNA species present in all tissues tested. Sequencing of cDNAs suggests that at least two forms of mRNA with alternative 5' ends are present within the cell. The mRNA with the longest open reading frame gives rise to a protein of 57 kDa. Although the sequence reported is novel, remarkable similarity is observed with two predicted protein sequences from partial DNA sequences generated by rice (Oryza sativa) and fruit fly (Drosophila melanogaster) genome projects. The degree of sequence conservation is comparable to that observed for highly conserved structural proteins, such as heat shock protein HSP70, and is greater than that of gamma-tubulin and heat shock protein HSP60. A more distant relationship to the group of clathrin-associated proteins suggests a possible role in vesicle structure or trafficking. In view of its ancient pedigree and a potential involvement in cellular architecture, we propose that the ARCN1 protein be named archain. PMID- 7782068 TI - Localization of a murine recessive polycystic kidney disease mutation and modifying loci that affect disease severity. AB - We have used a novel method of chromosomal exclusion to map the recessive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J) F1jck/ + mice. The severity of polycystic kidney disease (PKD) in the intercross progeny was significantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affects expression of jck. Two regions--one from DBA/2J on chromosome 10 and a second from C57BL/6J on chromosome 1--are associated with inheritance of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease severity, with a maximal QTL analysis lod score of 16.8, was unexpected; this result suggests that inheritance of both this locus and at least one DBA/2J locus results in the more severe phenotype, presumably as a consequence of a direct or indirect interaction between their protein products. PMID- 7782069 TI - Construction of a YAC contig spanning the Xq13.3 subband. AB - The loci involved in several X-linked mental retardation syndromes have been linked to the pericentromeric region of the X chromosome long arm (Xq12-q21). To isolate candidate genes for these diseases, we set up the construction of YAC contigs spanning this region. Two of these syndromes (the Juberg-Marsidi syndrome and the alpha-thalessemia mental retardation syndrome) have been recently linked, with high lod scores, to polymorphic probes previously assigned to Xq13.3. We therefore constructed a first YAC contig, encompassing this band, from DXS441 to PGK1. The physical map, deduced from the isolated clones, extends over 2.1 Mb of genomic DNA. Restriction analysis of the YAC contig allowed us to map precisely the loci previously assigned to that chromosomal region and to define their relative order. The validity of this physical map has been checked by comparing Sfi I digests of the YACs to genomic fragments obtained with the same enzyme. A cDNA selection approach, already performed with a previous partial contig, has been extended to cover the whole region. PMID- 7782070 TI - Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human. AB - The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei)F1 x SPRET/Ei backcross. The chromosomal locations of the human homologs were determined by Southern blot analysis of a DNA panel from human-rodent somatic cell hybrids, most of which contained a single human chromosome each. The gene for PC4 (Pcsk4 locus) mapped to mouse chromosome 10, close to the Adn (adipsin, a serine protease) locus and near the Amh (anti mullerian hormone) locus; in human, the gene was localized to chromosome 19. The gene for PC5 (Pcsk5 locus) mapped to mouse chromosome 19 close to the Lpc1 (lipocortin-1) locus and, in human, was localized to chromosome 9. The gene for PACE4 (Pcsk6 locus) mapped to mouse chromosome 7, at a distance of 13 cM from the Pcsk3 locus, which specifies furin, another member of this family of enzymes previously mapped to this chromosome. This is in concordance with the known close proximity of these two loci in the homologous region on human chromosome 15q25 qter. Pcsk3 and Pcsk6 mapped to a region of mouse chromosome 7 that has been associated cytogenetically with postnatal lethality in maternal disomy, suggesting that these genes might be candidates for imprinting. PMID- 7782071 TI - Assignment of a Polycomb-like chromobox gene (CBX2) to human chromosome 17q25. AB - A human clone corresponding to the homologue of the murine Polycomb-like gene M33 has been used to map this gene (CBX2) to human chromosomes. Both somatic cell hybrid panels and FISH on metaphase chromosomes have been used. These techniques gave a consistent localization, at the tip of the long arm of chromosome 17 (17q25). This localization, as well as the potential role of a mammalian Polycomb like protein, suggests a potential involvement in two different pathologies: the campomelic syndrome, an inherited disorder, and neoplastic disorders linked to allele loss already described in this region. PMID- 7782073 TI - Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers. AB - We report the chromosomal localization and a simple sequence repeat (SSR) in the cytosolic phospholipase A2 (cPLA2) gene in both human and rat. A (CA)18 repeat in the promoter of the rat gene was determined to exhibit length polymorphism when analyzed using the polymerase chain reaction (PCR) in 19 different inbred rat strains. Genotyping for this marker in 234 F2 progeny of a SHR x BN intercross mapped the gene to rat chromosome 13. Using a PCR strategy, a fragment of the promoter for the human gene was isolated, and a (CA)18 repeat was identified. Since this marker displayed a low heterozygosity index, we also identified a mononucleotide repeat in the promoter for cPLA2 that displayed a polymorphism information content value of 0.76. The human gene was mapped using fluorescence in situ hybridization (FISH) to chromosome 1q25. Of interest, the gene encoding the enzyme prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), which acts on the arachidonic acid product of cPLA2, was previously localized to this same chromosomal region, raising the possibility of coordinate regulation. Identification of intragenic markers may facilitate studies of polymorphic variants of these genes as candidates for disorders in which perturbations of the eicosanoid cascade may play a role. PMID- 7782072 TI - A physical map of chromosome 20 established using fluorescence in situ hybridization and digital image analysis. AB - The physical locations of 46 cosmid clones and 21 P1 clones were determined along the chromosome 20 axis relative to the p terminus (FLpter) using fluorescence in situ hybridization (FISH) and digital image microscopy. The cosmid clones were selected from the chromosomally enriched library LA20NC01. Nine P1 clones were selected from a pooled DuPont genomic library using PCR with primer pairs selected to amplify genetically mapped sequence-tagged sites. This information was used to relate the physical map to the genetic map. Twelve P1 clones were selected from the same library using PCR primer pairs that amplified known genes. Two of these, E2F and BCLX, had not been mapped previously. PMID- 7782074 TI - Physical maps of human alpha (1,3)fucosyltransferase genes FUT3-FUT6 on chromosomes 19p13.3 and 11q21. AB - Sialyl Lewis x and related fucosylated glycans are differentially expressed in human cells and form ligands for selectin adhesion receptors. alpha(1,3)Fucosyltransferases (FUTs) that complete their biosynthesis also show tissue specificity. We have established physical maps of the FUT3-6 loci to study regulation of this gene family. FUT4 has previously been localized to chromosome 11q21; FUT3, FUT6, and now FUT5 are localized to chromosome 19p13.3. Conventional and pulsed-field gel electrophoresis mapping of total genomic DNA and large genomic clones were used to generate a fine map of both loci, defining the order, orientation, and distances between FUTs. A P1 clone with all three 19p FUT genes in tandem orientation was isolated and used to study regions flanking FUT3, -5, and -6. Our studies provide preliminary information to study regulation of human FUT genes. PMID- 7782075 TI - Comparative mapping of DNA probes derived from the V kappa immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) of cosmid clones of human V kappa gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the kappa locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V kappa I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V kappa region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. PMID- 7782076 TI - Characterization of a large population of mRNAs from human testis. AB - We present the results of single-pass sequencing of 779 expressed sequence tags from normal human testis cDNA clones. Of the sequences generated, 319 (41%) appeared to be completely unknown and are likely to represent new genes, and 289 (37%) were identified based on exact or nonexact matches to sequences in public databases. In analyses of hybridization of four tissues, testis, brain, liver, and kidney, 6 of 12 cDNAs clones revealed testis-specific expression. This argues for the value of the combination of random sequencing and analysis of cellular expression for large-scale characterization of gene expression in the testis. PMID- 7782077 TI - Amelogenin signal peptide mutation: correlation between mutations in the amelogenin gene (AMGX) and manifestations of X-linked amelogenesis imperfecta. AB - Formation of tooth enamel is a poorly understood biological process. In this study we describe a 9-bp deletion in exon 2 of the amelogenin gene (AMGX) causing X-linked hypoplastic amelogenesis imperfecta, a disease characterized by defective enamel. The mutation results in the loss of 3 amino acids and exchange of 1 in the signal peptide of the amelogenin protein. This deletion in the signal peptide probably interferes with translocation of the amelogenin protein during synthesis, resulting in the thin enamel observed in affected members of the family. We compare this mutation to a previously reported mutation in the amelogenin gene that causes a different disease phenotype. The study illustrates that molecular analysis can help explain the various manifestations of a tooth disorder and thereby provide insights into the mechanisms of tooth enamel formation. PMID- 7782078 TI - Assignment of the human neuropeptide Y gene to chromosome 7p15.1 by nonisotopic in situ hybridization. PMID- 7782079 TI - The murine endoglin gene (Eng) maps to chromosome 2. PMID- 7782080 TI - Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization. PMID- 7782081 TI - Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization. PMID- 7782082 TI - Efficient pooling designs for library screening. AB - We describe efficient methods for screening clone libraries, based on pooling schemes that we call "random k-sets designs." In these designs, the pools in which any clone occurs are equally likely to be any possible selection of k from the v pools. The values of k and v can be chosen to optimize desirable properties. Random k-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, and easy to specify, require fewer pools, and have error-correcting and error-detecting capabilities. In addition, screening can often be achieved in only one pass, thus facilitating automation. For design comparison, we assume a binomial distribution for the number of "positive" clones, with parameters n, the number of clones, and c, the coverage. We propose the expected number of resolved positive clones--clones that are definitely positive based upon the pool assays--as a criterion for the efficiency of a pooling design. We determine the value of k that is optimal, with respect to this criterion, as a function of v, n, and c. We also describe superior k-sets designs called k-sets packing designs. As an illustration, we discuss a robotically implemented design for a 2.5-fold-coverage, human chromosome 16 YAC library of n = 1298 clones. We also estimate the probability that each clone is positive, given the pool-assay data and a model for experimental errors. PMID- 7782083 TI - Structure of the terminal 300 kb of DNA from human chromosome 21q. AB - The most distal 300 kb of human chromosome 21q was cloned and mapped using telomeric yeast artificial chromosomes (YACs). The region contains low-copy subtelomeric repeats at the telomeric end, chromosome 21-specific sequences more centromerically, and the S100B gene at a distance of 100-140 kb from the chromosome terminus. RecA-assisted restriction endonuclease cleavage of genomic DNA showed that the cloned fragments correspond to telomere-terminal genomic DNA, and restriction enzyme mapping of the YACs shows that the smaller clone (175 kb) corresponds exactly to the telomeric end of the larger one (300 kb). PCR assays for 21q-specific markers were used to show that COL6A1, COL6A2, and LA161 were all outside of the subtelomeric region spanned by the YACs and thus at least 300 kb from the 21q terminus. The molecular probes provide telomeric closure for existing 21q maps. PMID- 7782084 TI - A high-resolution genetic linkage map of the pericentromeric region of the human X chromosome. AB - We generated a high-resolution genetic linkage map of the pericentromeric region of the human X chromosome from approximately Xp11.4 to Xq22. This map contains 41 loci defined by 50 marker systems genotyped in the CEPH families. For this study we have generated 3 new markers (DXS1689, DXS1690, and DXS159) and 2 new primer sequences for previously described markers (PGK1P1 and AR). Using two different mapping algorithms based on genotype data alone, we developed two well-supported framework maps containing 15 and 18 markers with average interval sizes of 2.7 and 1.7 cM. The 18 marker map is [DXS426, PFC]-2.0-DXS255-1.2-DXS991-1.6-AR-1.3 DXS153-2.0-DX S106-1.5-DXS132-0.6- DXS1690-0.8-DXS453-1.4-DXS559-1.5-[PGK1, DXS56]-0.6-DXS1002-1.8-DXYS1X-2.0-DXS3-7.5-DX S458-2.8-DXS454, where the distance between adjacent loci is in centimorgans. As a third approach, we used physical mapping data to define bins for markers; this approach permitted us to place 26 markers on our framework map. Finally, we constructed a map based on the physical order of 35 markers from the fifth international workshop on human X chromosome mapping. A comparison of the physical and genetic maps indicates a relationship of 2 cM per megabase in this region, with two regions of reduced recombination. The first is around the centromere (DXZ1), and the second is in the region around PGK1 (DXS441 to DXS995). Our maps should aid in the fine-mapping of the many disease loci that localize to this region of the X chromosome. PMID- 7782085 TI - Molecular cloning of the microfibrillar protein MFAP3 and assignment of the gene to human chromosome 5q32-q33.2. AB - Microfibrils having a diameter of 10-12 nm, found either in association with elastin or independently, are an important component of the extracellular matrix of many tissues, but characterization of these microfibrils is incomplete. To further our understanding of the gene structure of proteins composing the microfibrils and to identify their chromosomal location, we have cloned and characterized another microfibril protein, designated microfibril-associated protein-3 (MFAP3). The human gene encoding MFAP3 has a very simple structure, containing only two translated exons encoding a protein of 362 amino acids. Monospecific antibodies prepared against the recombinantly expressed protein reacted with the microfibrils found in ocular zonules. MFAP3 does not appear to share homology with any other known protein. The gene was found to be located on chromosome 5q32-q33.2, near the locus 5q21-q31 reported for the fibrillin gene, FBN2, which has been linked to congenital contractural arachnodactyly. MFAP3 is a candidate gene for heritable diseases affecting microfibrils. PMID- 7782087 TI - Cloning, sequence analysis, and chromosomal assignment of the mouse Apex gene. AB - APEX nuclease (Apex gene product) is a mammalian multifunctional DNA repair enzyme possibly involved in the repair of apurinic/apyrimidinic (AP) sites and single-strand DNA breaks with 3' termini blocked by nucleotide fragments and also in transcriptional regulation via redox activation of the AP-1 transcription factors. We cloned a 15-kb DNA fragment containing the Apex gene from a mouse leukocyte genomic library and determined a 4-kb stretch of its nucleotide sequence, including the complete sequence of the mouse Apex gene. The gene consists of 5 exons and 4 introns spanning 2.21 kb, and the boundaries between exons and introns follow the GT/AG rule. Two major and one minor transcription initiation sites were assigned to positions +1 and +24 and position +14, respectively, by a combination of ribonuclease protection, primer extension, and 5' RACE analyses. Position +1 is located 312 nucleotides upstream from the ATG initiation codon. The translation initiation and termination sites are located in exon II and exon V, respectively. The sequenced 5' flanking region (1.32 kb) lacks a typical TATA box, but contains a CAAT box and putative binding sites for several transcription factors, such as ATF, NF-IL6, Sp1, and AP2. The 0.8-kb region from position -410 (5' flanking region) to position +386 (intron II) contains a CpG island. The Apex gene locus was mapped to mouse chromosome 14C2-D1 using in situ hybridization. PMID- 7782086 TI - Structural organization of the human sorbitol dehydrogenase gene (SORD). AB - The primary structure of human sorbitol dehydrogenase (SORD) was determined by cDNA and genomic cloning. The nucleotide sequence of the mRNA covers 2471 bp including an open reading frame that yields a protein of 356 amino acid residues. The gene structure of SORD spans approximately 30 kb divided into 9 exons and 8 introns. The gene was localized to chromosome 15q21.1 by in situ hybridization. Two transcription initiation sites were detected. Three Sp1 sites and a repetitive sequence (CAAA)5 were observed in the 5' noncoding region; no classical TATAA or CCAAT elements were found. The related alcohol dehydrogenases and zeta-crystallin have the same gene organization split by 8 introns, but no splice points coincide between SORD and these gene types. The deduced amino acid sequence of the SORD structure differs at a few positions from the directly determined protein sequence, suggesting allelic forms of the enzyme. High levels of SORD transcripts were observed in lens and kidney, as judged from Northern blot analysis. PMID- 7782088 TI - Characterization of the Xiphophorus fish (Teleostei: Poeciliidae) ERCC2/XPD locus. AB - We have cloned and sequenced the ERCC2/XPD locus of Xiphophorus maculatus. The human ERCC2/XPD gene is a nucleotide excision repair gene presumed to encode an ATP-dependent DNA helicase. The fish ERCC2/XPD gene is represented on 14.5 kb of genomic DNA and is composed of 23 exons. Within the coding regions, the overall nucleotide identity is 74% compared to the human cDNA. Of 760 amino acids compared between human and fish sequences, 127 differences are observed. Of these differences, 48 residues (38%) represent nonconservative amino acid changes, while 79 (62%) are conservative. The majority (73%) of nonconservative differences between the human and the fish amino acid sequences occur in eight distinct groups comprising only about 10% of the total protein. Overall, the fish and human sequences show 83% amino acid identity and 94% similarity when conservative amino acid substitutions are allowed. PMID- 7782089 TI - Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. AB - Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, we demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each other on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NPY and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event. PMID- 7782090 TI - Genomic mapping by end-characterized random clones: a mathematical analysis. AB - Physical maps can be constructed by "fingerprinting" a large number of random clones and inferring overlap between clones when the fingerprints are sufficiently similar. E. Lander and M. Waterman (Genomics 2: 231-239, 1988) gave a mathematical analysis of such mapping strategies. The analysis is useful for comparing various fingerprinting methods. Recently it has been proposed that ends of clones rather than the entire clone be fingerprinted or characterized. Such fingerprints, which include sequenced clone ends, require a mathematical analysis deeper than that of Lander-Waterman. This paper studies clone islands, which can include uncharacterized regions, and also the islands that are formed entirely from the ends of clones. PMID- 7782091 TI - Localization of new genes and markers to the distal part of the human major histocompatibility complex (MHC) region and comparison with the mouse: new insights into the evolution of mammalian genomes. AB - We have refined and extended the map of the distal half of the human major histocompatibility complex. The map is continuous from HLA-E to 1000 kb telomeric of HLA-F and includes six new markers and genes. In addition, the corresponding sequences that were not previously mapped in the mouse genome have been located. The human and the mouse organizations have therefore been compared. This comparison allows us to demonstrate that the structure of the distal part of the MHC is similar in the two species. In addition, this comparison shows the presence of a breakpoint of synteny telomeric of the distal part of the H-2 region. Indeed, the region telomeric of HLA in human is found on a chromosome different from that carrying H-2 in mouse. The mapping analysis of paralogous genes (structurally related genes) around the breakpoint shows that the human organization probably represents the putative human/mouse ancestral one. This evolutionary breakpoint was precisely mapped in human, and the surrounding region was cloned into yeast artificial chromosomes. Finally, we show that the region found around the breakpoint was involved several times in chromosome recombinations in the mouse lineage, as it seems to correspond also to the t complex distal inversion point. PMID- 7782092 TI - Promotion of macrophage-stimulated autoreactive T cell proliferation by interleukin-10: counteraction of macrophage suppressor activity during tumor growth. AB - CD4+ autoreactive T cells are a major cell population in regulating immune responses to altered autologous neoplastic cells. Normal autoreactive T cells recognize major histocompatibility complex (MHC) class II molecules in association with self-peptides on antigen-presenting cells, such as macrophages (M phi). Tumor-bearing hosts (TBH) have decreased autoreactivity partly because tumors increase M phi secretion of suppressor molecules like prostaglandin E2 (PGE2) and decrease M phi MHC class II expression. Because interleukin (IL)-10, a cytokine produced by T cells, M phi, and tumor cells, inhibits production of most M phi suppressor molecules, we determined if IL-10 could reverse tumor-induced murine splenic M phi-mediated suppression of autoreactive T cell proliferation. Tumor growth enhanced activated M phi production of PGE2, nitric oxide, and tumor necrosis factor-alpha (TNF-alpha). IL-10 strongly reduced or inhibited M phi production of these molecules. When added to pure normal host (NH) CD4+ T cells, NH syngeneic splenic M phi stimulated autoreactive T cell proliferation more than did TBH splenic M phi. Exogenous IL-10 or M phi preincubation with IL-10 restored TBH M phi-stimulated autoreactivity to normal levels. IL-10 treatment had little or no effect on NH M phi-stimulated autoreactivity. IL-10 inhibited TBH M phi secretion of suppressor molecules in T cell proliferation assays because supernatants from IL-10-pretreated TBH M phi-syngeneic NH T cell cultures had decreased levels of suppressor molecules. When endogenous IL-10 activity was neutralized with anti-IL-10 monoclonal antibody, autoreactive T cell proliferation stimulated by NH or TBH M phi was slightly, but significantly decreased. Although IL-10 is known to inhibit M phi foreign antigen-presenting cell-dependent T cell proliferation, this study shows that IL-10 restores autoreactive T cell functions during tumor growth by counteracting M phi production of inhibitory molecules. These data suggest that IL-10 up-regulates anti-cancer autoreactive T cell responses by down-regulating suppressor M phi activity. PMID- 7782093 TI - A function of Ly-5 (CD-45) in the generation of lymphokine-activated killer cells defined by Ly-5 anti-sense oligodeoxyribonucleotides and Ly-5 monoclonal antibody. AB - The unique feature of the Ly-5 system is that it is a major cell surface glycoprotein, representing up to 10% of the total cell surface complement, confined to the hematopoietic cells as a family of isoforms generated by alternative splicing of a single Ly-5 gene. The cytoplasmic domain of Ly-5 has protein tyrosine phosphatase activity suggesting that Ly-5 is involved in signal transduction. We used Ly-5 anti-sense oligodeoxyribonucleotides (oligo) and Ly-5 monoclonal antibody (mAb) to study the functional role of Ly-5 in the concanavalin A mitogenesis response by spleen cells, as well as in the generation of lymphokine-activated killer cells and the proliferative response by spleen cells induced by recombinant human interleukin-2 (rhIL-2). Our results indicate that the Ly-5 mAb could enhance these activities whereas the anti-sense oligo was inhibitory. These data clearly suggest that Ly-5 is involved in the IL-2 and IL-2 receptor responsive circuit. PMID- 7782094 TI - Expression of MHC class II antigens on rat bone marrow cells and macrophages, and their modulation during culture with murine GM-CSF or M-CSF. AB - Flow cytometric analysis employing MRC OX 6 and MRC OX17 monoclonal antibodies recognizing determinants on RT1.B or RT1.D molecules, equivalent to murine I-A and I-E, respectively, was used to detect rat MHC class II antigen (Ag) expression. Approximately 5% of freshly isolated rat bone marrow cells (BMC) expressed RT1.B and over 30% displayed RT1.D molecules. The RT1.D+ cells were W3/13+, OX 7+, OX 19- and OX 22-. After one week culture of BMC with murine recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF), regardless of concentrations, 90 to 95% of the cells were scored as bone marrow-derived macrophages (BMDM phi), and over 30% expressed both RT1.B and RT1.D Ag. GM-CSF increases the percentage of BMDM phi bearing MHC class II Ag in a concentration dependent manner. This effect seems to be specific because antibodies to interferon-gamma, tumor necrosis factor-alpha or interleukin-4 did not reduce the number of cells expressing RT1.B and RT1.D Ag. Furthermore, GM-CSF was able to trigger expression of class II molecules on rat peritoneal macrophages (M phi) and BMDM phi resulted from cultures of BMC with mouse M phi-CSF (M-CSF), and the RT1.B and RT1.D inducing effect of GM-CSF was opposed by M-CSF, and by anti-GM CSF antibodies. The induction of MHC class II Ag synthesis by GM-CSF on rat BMDM phi was confirmed at the mRNA level by Northern blot analysis employing cDNA probes encoding the RT1.B alpha. PMID- 7782095 TI - Antiproliferative effect of bone marrow cells on leukemic cells. AB - When normal murine bone marrow (BM) cells were cultured with either L1210 lymphoma cells or P815 mastocytoma cells for 24 h, considerable tumor growth suppression without substantial tumor cell lysis was found. Under the same conditions, normal spleen cells also demonstrated the antitumor cytostatic activity, but not as significant as that characteristic of BM cells, whereas both normal thymus and lymph node cells had not any suppressive effect on tumor cell proliferation. The comparable cytostatic effects occurred in both syngeneic and allogeneic BM-tumor cell combinations. The cytostatic BM-effectors were distinct from T and B lymphocytes or mature macrophages. After being separated on a discontinuous Percoll density gradient, the cells active in suppressing tumor growth were recovered predominantly in 1.075 and 1.060 density fractions. The cytostatic BM effectors, at least in their part, were resistant to x-irradiation up to 2000 rad included. Collectively these results suggest that normal BM, being deficient in cell-mediated antitumor cytolytic activity, has a significant leukemia growth inhibitory potential; and that cytostatic BM effectors are similar in their characteristics to natural suppressor cells. PMID- 7782096 TI - Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. AB - The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels. PMID- 7782097 TI - Changes in the blood-thymus barrier of adult rats after estradiol-treatment. AB - The accessibility of the thymus parenchyma for relatively large Mw (+/- 150 Kd) proteins has been studied by the intravenous injection of monoclonal antibodies (mAbs) specific either for all T cells (His-17) or MHC class II molecules (His 19) in control and estradiol benzoate (EB)-treated adult Wistar rats. In controls, the transcapsular route rather than cortical capillaries seems to be involved in the entry of molecules into the thymus. By contrast, a specific staining for either T cells (His-17) or MHC class II molecules (His-19 positive cells) disappears almost completely from the thymic cortex of EB-treated rats except in the immediate subcapsular epithelial cell layer. In these rats, T cells and epithelial cells intimately associated to blood vessels from both inner cortex and corticomedullary border showed additional staining with the respective mAbs confirmed by electron microscopy. The disappearance of the transcapsular route together with the increased vascular permeability of cortical blood vessels would be related to the reinforcement of the subcapsular epithelial cell layer and to direct effects of EB on vascular endothelia, respectively. These results are discussed in relationship to the cell migration into and out of adult thymus, as suggested by the changes in intrathymic T cell subsets evaluated by flow cytometry. PMID- 7782098 TI - Expression of ICAM-3 on human epidermal dendritic cells. AB - Three counter-receptors for LFA-1 of the immunoglobulin family have been discovered: ICAM-1, ICAM-2, and ICAM-3. Despite their homologies, their patterns of expression suggest specialized roles. The finding that ICAM-3 is much better expressed than other LFA-1 ligands on monocytes and resting T cells, and that this discovery may be important in the initiation of immune responses prompted us to search for the expression of ICAM-3 by human epidermal Langerhans cells (LC). Six out of eight different ICAM-3 monoclonal antibodies were found to be reactive with epidermal LC. Immunoelectron-microscopy staining revealed that 100% of freshly-isolated, typical Birbeck granules containing LC expressed ICAM-3. After one day and three days of culture, 100% of LC still expressed ICAM-3, but the staining intensity was decreased by 58% and 76% respectively. Immunoprecipitation of 125I surface-labeled LC with anti-ICAM-3 antibodies revealed a polypeptide with apparent M(r) of 122,000-125,000. To determine whether ICAM-3 was involved in LC function, mixed epidermal cell-lymphocyte reactions were performed with freshly isolated LC in the presence of various concentrations of different anti ICAM-3 antibodies. Among the different antibodies tested, HP2/19 and CBR-IC3/1 were found to partially block the reaction in a dose-dependent manner, suggesting that ICAM-3 represents a new molecule involved in the initiation of the immune response driven by epidermal LC. PMID- 7782099 TI - Human nonspecific suppressor factor (hNSF): cell source and effects on T and B lymphocytes. AB - The human nonspecific suppressor factor (hNSF), the probable counterpart of the murine monoclonal nonspecific suppressor factor (MNSF), has been isolated from the ascitic fluid of a patient with systemic lupus erythematosus and characterized. hNSF presents an inhibitory activity on the proliferation and IgG production of mitogen stimulated human PBMC. In the present study, we demonstrate that hNSF can be isolated from the supernatants of ConA-activated T cells, but not from CD8-depleted T cells, indicating the CD8+ T cells are the major source of the factor. We also studied the effects of hNSF on purified human B and T cells; hNSF strongly inhibited the proliferation and Ig secretion by highly purified B cells induced by SAC plus IL-2, as well as the proliferation of T cells activated by Con A plus IL-2. These results indicate that hNSF is a CD8+ T cell product with strong antigen-nonspecific immunoregulatory action on both lymphocyte populations. PMID- 7782100 TI - Characterization of platelet antigen for CD45RA monoclonal antibodies. AB - CD45RA monoclonal antibodies recognize the higher molecular weight isoforms (220 and 205 kDa) of leukocyte common antigen family (CD45), which are typically expressed on B cells and unstimulated T cells. We have found that there are at least three distinct CD45RA monoclonal antibodies which react with platelet 42 kDa (P42) intracellular protein antigen, which seems to be different from any to date described platelet proteins with similar molecular weight. This platelet antigen is a single chain protein, very likely not a glykoprotein, with isoelectrical point between 6.8 and 7.5. P42 does not seem to be a membrane protein and is not associated with platelet cytoskeleton. Results of immunofluorescence assay suggest that P42 may be redistributed to platelet surface after platelet aggregation. PMID- 7782101 TI - Glial cell types, lineages, and response to injury in rat and fish: implications for regeneration. AB - Axons of the mammalian central nervous system do not regenerate spontaneously after axonal injury, unlike the central nervous system axons of fish and amphibians and the peripheral nervous system of mammals, which possess a good regenerative ability (Grafstein: The Retina: A Model for Cell Biology Studies, Part II, 1986; Kiernan: Biol Rev 54:155-197, 1979; Murray: J Comp Neurol 168:175 196, 1976; Ramon y Cajal: Degeneration and Regeneration of the Nervous System, 1928; Reier and Webster: J Neurocytol 3:591-618, 1974; Sperry: Physiol Zool 23:351-361, 1948). It was previously believed that intrinsic differences between the central nervous system neurons of mammals and fish account for their differences in regenerative ability. The past decade, however, has seen an accumulation of evidence, indicating that mammalian central nervous system neurons are able to regenerate injured axons, at least to some extent. This was first demonstrated by Aguayo and colleagues (David and Aguayo: Science 214:931 933, 1981; Kierstead et al: Science 246:255-257, 1989), who showed that injured mammalian central nervous system axons can grow for a considerable distance into an autograft of a peripheral nerve. It was also demonstrated that injured rabbit optic axons can regenerate into their own environment (i.e., into the distal part of the injured optic nerve), if the injured nerve is treated so as to make it conducive for growth (Lavie et al: J Comp Neurol 298:293-314, 1990; Eitan et al: Science 264:1764-1768, 1994).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782102 TI - Differential Na+ channel beta 1 subunit mRNA expression in stellate and flat astrocytes cultured from rat cortex and cerebellum: a combined in situ hybridization and immunocytochemistry study. AB - Astrocytes have been shown to express voltage-sensitive Na+ channels, but the molecular structure of these channels is not yet known. Recent studies have demonstrated the expression of rat brain voltage-sensitive Na+ channel mRNAs in astrocytes. In this study, we used a combined non-radioactive in situ hybridization/immunocytochemistry method to investigate the expression of voltage sensitive Na+ channel beta 1 subunit (Na beta 1) mRNA in definitively identified, GFAP-positive astrocytes cultured from two different regions of the rat brain, cerebrum and cerebellum. In general, two morphologically distinct types of GFAP positive astrocytes were observed in culture: flat, fibroblast-like and stellate, process-bearing. We observed a differential expression of Na beta 1 mRNA in GFAP positive astrocytes: 1) stellate astrocytes expressed Na beta 1 mRNA, although the level of Na beta 1 mRNA expression was variable, and 2) flat astrocytes generally did not express Na beta 1 mRNA. Moreover, Bergmann-like cells from cerebellum did not express Na beta 1 mRNA, while the granule cells associated with Bergmann-like cell expressed Na beta 1 mRNA. These observations indicate that Na beta 1 mRNA is differentially expressed in rat astrocytes with various morphologies in vitro. PMID- 7782104 TI - The receptor for tumor necrosis factor on murine astrocytes: characterization, intracellular degradation, and regulation by cytokines and Theiler's murine encephalomyelitis virus. AB - Previous reports have shown that tumor necrosis factor (TNF) exerts a role on the physiology of astrocytes under inflammatory situations. The signalling for biological effects of this and other cytokines are usually exerted through cell surface receptors. In this study, we have demonstrated the presence of a surface TNF alpha receptor type I in murine astrocytes of both SJL/J and BALB/c origin, using 125I-labelled recombinant mouse TNF alpha. A linear Scatchard plot indicates the presence of only one type of receptor with a MW of 58 kDa (Type I TNF receptor) that binds the ligand with a Kd of 1 x 10(-9) M. There are 3,000 copies of this receptor on untreated astrocytes. The results also indicate that receptor-bound TNF is rapidly internalized at 37 degrees C and degraded intracellularly to a principal molecular species which elutes from HPLC reverse phase columns at 38% acetonitrile rather than at 60%, as native TNF alpha does. The binding is up-regulated by increasing the number of receptors (but not its affinity) by treatments with Theiler's murine encephalomyelitis virus (TMEV), Con A and inflammatory cytokines such as IL-1 alpha, IL-6, and INF-gamma. It is not influenced by vaccinia virus, IL-2, or LPS. This receptor may contribute to the initiation of perpetuation of the immune response which mediates the demyelinating inflammation induced by Theiler's virus. PMID- 7782103 TI - Indicator expression directed by regulatory sequences of the glial fibrillary acidic protein (GFAP) gene: in vivo comparison of distinct GFAP-lacZ transgenes. AB - An increase in the expression of the glial fibrillary acidic protein (GFAP) gene by astrocytes appears to constitute a crucial component of the brain's response to injury because it is seen in many different species and features prominently in diverse neurological diseases. Previously, we have used a modified GFAP gene (C-339) to target the expression of beta-galactosidase (beta-gal) to astrocytes in transgenic mice (Mucke et al.; New Biol 3:465-474 1991). To determine to what extent the in vivo expression of GFAP-driven fusion genes is influenced by intragenic GFAP sequences, the E. coli lacZ reporter gene was either placed downstream of approximately 2 kb of murine GFAP 5' flanking region (C-259) or ligated into exon 1 of the entire murine GFAP gene (C-445). Transgenic mice expressing C-259 versus C-445 showed similar levels and distributions of beta-gal activity in their brains. Exclusion of intragenic GFAP sequences from the GFAP lacZ fusion gene did not diminish injury-induced upmodulation of astroglial beta gal expression or increase beta-gal expression in non-astrocytic brain cells. These results demonstrate that 2 kb of murine GFAP 5' flanking region is sufficient to restrict transgene expression primarily to astrocytes and to mediate injury-responsiveness in vivo. This sequence therefore constitutes a critical target for mediators of reactive astrocytosis. While acute penetrating brain injuries induced focal increases in beta-gal expression around the lesion sites in C-259, C-445, and C-339 transgenic mice, infection of C-339 transgenic mice with scrapie led to a widespread upmodulation of astroglial beta-gal expression. Hence, GFAP-lacZ transgenic mice can be used to monitor differential patterns of astroglial activation in vivo. These and related models should facilitate the assessment of strategies aimed at the in vivo manipulation of GFAP expression and astroglial activation. PMID- 7782105 TI - Effects of enhanced extracellular ammonia concentration on cultured mammalian retinal glial (Muller) cells. AB - Muller (glial) cells of the neonatal rabbit retina were cultured as confluent monolayers and exposed to enhanced concentrations of ammonia (0.25, 0.5, 1, 3, 7, and 10 mM) in medium for various periods (30 min to 10 d). This caused, in a time and dose-dependent manner, similar changes in the Muller cells as had previously been described in cultured astrocytes. The most conspicuous events were 1) an increasing size of cell nuclei, 2) an accumulation of phagocytotic vacuoles, and 3) a rearrangement of intermediate filaments. 4) A considerable number of cells died when higher ammonia concentrations were applied for more than 1 h. Simultaneous application of dibutyryl-cyclic adenosine monophosphate (dBcAMP) prevented almost completely both the increase in cell nucleus size and the changes of intermediate filaments, but only partly the early cell death of a subpopulation of cells, and the accumulation of phagocytotic vacuoles. Further changes evoked by enhanced ammonia concentration were 5) an accumulation of lipofuscin-like material ("fatty degeneration") revealed by lipophilic stain, 6) reduced immunoreactivity for cathepsin D, and increased immunoreactivity for 7) glial fibrillary acidic protein, 8) glutamine synthetase, and 9) bcl-2 protooncogene protein. These findings are discussed in respect to the possible underlying pathophysiological mechanisms. PMID- 7782106 TI - Estradiol promotion of changes in the morphology of astroglia growing in culture depends on the expression of polysialic acid of neural membranes. AB - Gonadal steroids are known to affect astroglial morphology in developing and adult animals. Earlier studies of mixed neuronal-glial cultures from fetal rat hypothalamus showed that glial fibrillary acidic protein (GFAP)-immunoreactive cells with a polygonal shape were transformed into process-bearing cells upon exposure to the ovarian hormone estradiol. This effect was dependent on a direct contact of astroglia with living hypothalamic neurons. The present study shows that somata and processes of neurons in such cultures were immunoreactive for polysialic acid (PSA); astroglia were immunonegative. PSA appears to participate in the estradiol-induced shape changes since treatment with endoneuraminidase, an enzyme that specifically removes PSA from the cell surface, abolished PSA immunostaining and prevented the 17 beta-estradiol-induced morphological changes of astroglia. In contrast, treatment with endoneuraminidase did not affect astroglial shape changes induced by basic fibroblast growth factor (bFGF), nor those induced by the addition of neurons to glial cultures. These results suggest that PSA on neuronal membranes, probably linked to the highly sialylated isoform of the neural cell adhesion molecule, is necessary for the expression of certain hormonally-regulated neuro-glial interactions. PMID- 7782107 TI - Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes. AB - Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP and vimentin, was observed surrounding the neocortical lesion site. Astrocytes and pial cells situated adjacent to the area of injury also became positively stained for metallothionein. At 3-6 days post-lesion, the highest level of reactive astrocytes expressing metallothionein was observed. Neo-Timm staining revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallothionein positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain induces a transient expression of metallothionein in reactive astrocytes, probably as a response to metals released from the site of the brain injury. PMID- 7782108 TI - Expression of NMDA 2B receptor subunit mRNA in Bergmann glia. AB - N-methyl-D-aspartate (NMDA)-activated glutamate receptor subunits are invariably expressed in neurons, although NMDA-activated currents have been recently described in Bergmann glia. To date, the NMDA receptor subunit 2B (NMDAR2B) was thought not to be expressed in adult cerebellum. In the present study we provide evidence, from in situ hybridization histochemistry, that Bergmann glial cells in rat brain express mRNA encoding the NMDAR2B subunit, most probably co-expressed with the ubiquitous NMDAR1 subunit, while transcripts for other NMDAR2 subunits (A,C,D) were either not resolved or detected. Our findings suggest that Bergmann glial cells contain the molecular machinary to synthesize the NMDA receptor 2B subunit. The role of physiological NMDA receptors in the interaction between Bergmann glia and Purkinje neurons is not yet known. PMID- 7782109 TI - Clinical relevance of intracellular and extracellular concentrations of macrolides. AB - The serum levels of the three macrolides--roxithromycin, clarithromycin and azithromycin--vary considerably. The prediction of the antibacterial effect against extracellular pathogens is based on circulating concentrations of free drug, peak and trough levels, the rate of killing, and the presence of a post antibiotic effect. Intracellular activity depends on the distribution of the antibiotic and the localization of the bacteria, and is variable. Roxithromycin uptake is greater than that of erythromycin. The intracellular half-life may be long for some compounds (azithromycin > roxithromycin). The intracellular distribution is bimodal, both in the lysosomes and the cytoplasm, but the mechanisms of uptake have not yet been established. At low pH, accumulation is low and macrolides are less active in an acidic medium. Intracellular concentrations cannot readily be predicted on the basis of extracellular levels. Different models have shown that the greater the intracellular concentration, the better the clinical effect. In addition, the transport of macrolides by cells into the infected focus may play an important role in the therapeutic outcome. These factors influence the clinical indications for macrolides, their dosing regimens and breakpoints. In future, macrolides will be developed that are more selective for intracellular infections, while others, which will achieve significant serum levels, will be useful for a broader range of diseases. However, new compounds should be evaluated in different models of infection before clinical studies are instituted. The analysis of failures remains the most important approach in defining concentration/effect relationships. PMID- 7782110 TI - Roxithromycin 150 mg b.i.d. versus amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for the treatment of lower respiratory tract infections in general practice. AB - Two hundred and forty-two patients over 16 years of age with community-acquired lower respiratory tract infection (LRTI), matched for age and sex, were randomised to receive either roxithromycin 150 mg b.i.d. or amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for 7 days, with a further 7 days if insufficient response was seen. Clinical efficacy at 7 days was 69% for roxithromycin and 56% for amoxycillin/clavulanic acid (p = 0.05) and at study end it was 91% for both antibiotics. There were fewer second treatment courses in the roxithromycin group (26% vs. 38%, p = 0.04) and a shorter treatment duration (8.29 days vs. 9.34 days, p > 0.05). Twelve patients (9.8%) treated with roxithromycin and 19 (17.1%) treated with amoxycillin/clavulanic acid had adverse effects possibly, or probably, related to the antibiotic. Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, greater cost-effectiveness, more convenient dosage regimen (b.i.d.), and superior tolerability profile. PMID- 7782111 TI - Pharmacoeconomic evaluation of roxithromycin versus amoxycillin/clavulanic acid in a community-acquired lower respiratory tract infection study. AB - A cost-effectiveness study of roxithromycin versus amoxycillin/clavulanic acid using data from a 242 patient multicentre trial in Australia and New Zealand was undertaken in the general practice treatment of infections of the lower respiratory tract (LRTI). Those patients assigned to roxithromycin required on average 1 day less of treatment, significantly fewer extended courses of treatment, and fewer patients experienced side effects considered to be related to the treatment. The cost benefit (difference between the two treatment costs) per clinical success was A$17.04*. By substituting roxithromycin for amoxycillin/clavulanic acid, Australia would save A$ 1.704 million per 100,000 episodes of LRTI. The results demonstrate that savings in direct costs can be achieved by substituting roxithromycin for amoxycillin/clavulanic acid in the treatment of community-acquired LRTI. PMID- 7782112 TI - The overall safety of oral roxithromycin in paediatric clinical studies. AB - In two multicentre, non-comparative studies, a total of 477 children, aged 2 months to 15 years, suffering from respiratory tract infections or skin and soft tissue infections were treated with roxithromycin (50 mg sachets). The mean duration of treatment was 9 days and the mean daily dose was 6 mg/kg/day administered b.i.d. The overall safety of roxithromycin was assessed by analysing the adverse events reported by the patients or investigators, the discontinuation of treatment because of adverse events, and the laboratory data. Adverse events reported by 20 (4%) children were considered to be possibly drug related. These adverse events were mainly digestive in nature and mild or moderate in severity. Treatment was discontinued because of adverse events in six (1%) children. Analysis of laboratory data revealed a few variations without any clinical significance. PMID- 7782113 TI - Potential role of roxithromycin against the Mycobacterium avium complex. AB - Until the recent experience with azithromycin and clarithromycin, macrolides were not considered to be important agents against mycobacteria. Clinical evidence is now growing that the newer 14 and 15 membered macrolide compounds have therapeutic activity against Mycobacterium avium, Mycobacterium chelonae and Mycobacterium leprae. Several years ago, when evaluating the activity of roxithromycin using one of the more virulent M. avium in our collection, the authors found that roxithromycin exerted a bacteriostatic effect in cultured human macrophages. However, in combination with tumour necrosis factor, which induces macrophage activation, roxithromycin caused enhanced intracellular killing. The significance of this finding is that tumour necrosis factor can be elaborated by activated macrophages during the course of infection. The roxithromycin doses that were chosen for these studies were less than achievable blood levels. More recently, the in vitro effect of roxithromycin against a panel of isolates from AIDS patients has been assessed and it was found that some (but not all) of the inhibitory concentrations, by the T-100 method of Inderlied, are within achievable serum levels. This, however, may not be the basis for anticipating in vivo activity since macrolide compounds are known to be concentrated within cells and particularly within phagolysosomes. Demonstration of effect in an in vitro test system is encouraging, but should be considered only as a preliminary step to careful assessments in experimental animals, such as the beige mouse, and studies in humans. PMID- 7782114 TI - Prevention of Pneumocystis carinii pneumonia and of cerebral toxoplasmosis by roxithromycin in HIV-infected patients. AB - The prevention of cerebral toxoplasmosis and of Pneumocystis carinii pneumonia is an essential objective in the management of patients infected with HIV. Given that roxithromycin is active in vitro against Toxoplasma gondii and that in 1989 Dolermann reported the effective treatment of P. carinii respiratory infections with erythromycin, a randomized pilot study was undertaken in 52 patients infected with HIV. Patients were treated with either: a monthly dose of pentamidine aerosol (300 mg); roxithromycin once a week (300 mg t.i.d.); or a combination of pentamidine aerosol and roxithromycin. Intention to treat analysis was applied to these 52 patients, all of whom received at least one treatment dose. Five out of 18 patients treated with pentamidine aerosol, 1/17 patients treated with pentamidine aerosol + roxithromycin and none of the 17 patients treated with roxithromycin developed cerebral toxoplasmosis (p = 0.038). P. carinii pneumonia was diagnosed in one patient in the pentamidine aerosol-treated group, in one patient treated with roxithromycin and in none of the patients treated with pentamidine aerosol + roxithromycin (non-significant difference). Four cases of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare infection were seen in the pentamidine aerosol-treated group (p = 0.028) and none in the roxithromycin groups. Adverse events leading to the discontinuation of treatment occurred in 5/34 (14.7%) patients treated with roxithromycin. Nausea, abdominal pain and raised transaminases occurred in four patients and a skin allergy in the final patient. Roxithromycin appears to be effective in the prevention of pulmonary pneumocystis infection and of cerebral toxoplasmosis in HIV-infected patients. However, these results require confirmation in a larger study. PMID- 7782115 TI - Roxithromycin in the treatment of Lyme disease--update and perspectives. AB - Spirochaetal infections have been successfully treated with penicillin; more recently, erythromycin has been used in cases with known penicillin allergy. The discovery of the spirochaete Borrelia burgdorferi and the elaboration of a new generation of macrolides with properties that differ from older macrolides have led to new ways of treating spirochaetal disease with these compounds. This paper presents data on the in vitro and in vivo efficacy of a combination of roxithromycin and co-trimoxazole against B. burgdorferi. In vitro (checkerboard technique; B. burgdorferi strain B31; modified BSK II medium) it was found that while roxithromycin showed excellent efficacy against B. burgdorferi (MIC 0.031 mg/l), co-trimoxazole had no effect. However, the combination of both chemotherapeutics led to a minor synergistic effect, decreasing the MIC for roxithromycin by one dilution step at concentrations of co-trimoxazole from 256 to 8 mg/l. In addition, a clearly reduced growth of microorganisms was seen at concentrations of roxithromycin as low as 0.015 mg/l in combination with 256 to 4 mg/l co-trimoxazole, when compared to the positive controls. Most interestingly, however, the motility of B. burgdorferi was markedly reduced even when the two drugs were combined at very low concentrations. In an in vivo, non-randomised, open, prospective pilot study it was found that of 17 patients with confirmed late Lyme borreliosis (stage II/III), treated with combined roxithromycin (300 mg b.i.d.) and co-trimoxazole for 5 weeks, 13 (76%) recovered completely by the end of treatment, and four continued to have symptoms on follow-up at 6 and 12 months. This success rate is similar to that seen with i.v. penicillin and ceftriaxone. It appears that the reduced motility of B. burgdorferi makes the pathogen more accessible to the immune system. PMID- 7782116 TI - Helicobacter pylori: the place of the new macrolides in the eradication of the bacteria in peptic ulcer disease. PMID- 7782117 TI - Pharmacokinetics of macrolides. Comparison of plasma, tissue and free concentrations with special reference to roxithromycin. AB - When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtained with roxithromycin, followed by clarithromycin and azithromycin. The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin. With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen. Intra-group subject variations (adults, children, the elderly etc.) were smaller than anticipated. Roxithromycin is found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour. PMID- 7782118 TI - Monitoring exposure of hospital personnel handling cytostatic drugs and contaminated materials. AB - A study was undertaken to evaluate the urine mutagenicity of 63 individuals working in four hospital departments. The exposed group included 38 subjects who were exposed to various cytostatic drugs and/or contaminated material from treated patients. The control group included 25 individuals of the hospital personnel. Urine mutagenicity was monitored by the Ames test using tester strains TA 98 + S9 Mix and TA 102-S9 Mix. Urine samples were collected before and after the working periods. A total of 29/116 (25%) urine samples were mutagenic for either strain. Among the mutagenic samples, 24/29 were mutagenic for tester strain TA 98 exclusively. No significant correlation could be found between occupational exposure to cytostatic drugs and urine mutagenicity evaluated by the strain TA 98 + S9 Mix. Smoking was the main environmental factor that modulated urine mutagenicity with TA 98. Three subjects in the exposed group had mutagenic urine samples at the end of the working period with strain TA 102-S9 Mix. This mutagenicity was related to occupational exposure to cisplatin. In the control group, one individual had mutagenic samples before and after the working period. Assessing occupational exposure to cytostatic drugs with strain TA 102 requires additional studies to determine environmental mutagens which can be detected by this strain. PMID- 7782120 TI - A case-control study of psychological and psychosocial risk factors for shoulder and neck pain at the workplace. AB - Risk factors associated with work-related shoulder and neck myalgia were investigated in a case-control study with pairs matched for age, gender, and physical exposure. Guided interviews with standardized and self-constructed questionnaires were performed among manual (n = 15 pairs) and office (n = 24 pairs) workers. Perceived general tension was the variable with the strongest association with shoulder and neck pain in both work groups. Otherwise, the results in the two groups were very different, indicating that different risk factors and mechanisms were associated with shoulder and neck pain in the two work groups. The study provides background information for future attempts to establish causal relationships between physical and psychosocial exposure and shoulder and neck pain, which can be more accurately investigated in a longitudinal rather than a cross-sectional experimental design. PMID- 7782119 TI - Dampness and molds in day-care centers as an occupational health problem. AB - To assess the occurrence of respiratory and other symptoms among workers in relation to dampness in day-care centers, a random sample of 30 day-care centers in the city of Espoo, Finland, was selected for the study. The study population consisted of 268 female day-care workers, who filled in a questionnaire. Dampness was found to be common: water damage had taken place in 70% of the centers, and workers perceived mold odor in 17% of them. Adjusted risk of work-related eye and respiratory symptoms was in general higher among the day-care workers exposed to both water damage and mold odor than among the unexposed. The prevalence of eye symptoms was statistically significantly higher. The results provide new evidence of the importance of dampness and mold problems in the work environment as determinants of respiratory and irritative symptoms. PMID- 7782121 TI - Subtle increase in leukocyte counts in association with drinking and smoking habits. AB - Peripheral leukocyte counts were examined in venous blood of more than 800 male workers exposed to toluene, xylenes, a combination of the two, or neither. Information on the social habits of smoking and drinking was obtained in an occupational health interview. The analysis showed that smoking (15 cigarettes/day on average) induced a significant increase (by 7%) in leukocyte counts, and that an additional increase was induced when the drinking habit was coupled with smoking. Drinking alone tended to increase the leukocyte counts but the effect was statistically nonsignificant, possibly because the number of nondrinking smokers was limited. The study stresses the importance of paying attention to smoking and drinking habits when evaluating hematological parameters such as peripheral leukocyte counts in solvent-exposed workers. PMID- 7782122 TI - Neurotoxicity induced by lead levels: an electrophysiological study. AB - The object of the present study was to evaluate, with the aid of visual evoked potentials (VEPs), modifications induced in the optic nerve by lead, and to investigate the relationship between blood lead levels (PbB) and modification of the VEP. We studied a sample of 300 men with PbB values between 17 and 60 micrograms/100 ml. Our study demonstrates that alterations in the latency of the VEP are dependent on PbB levels, though there is not a directly proportional relationship. PMID- 7782123 TI - Influence of power tool-related parameters on the response of finger flexor muscles. AB - Surface electromyography (EMG) and statistical analysis techniques were applied to investigate the response of finger flexor muscles to hand-transmitted vibration in all the three orthogonal directions. The trends in measured data were examined to derive the influence of variations in the tool-related parameters. Single-factor and multi-factor statistical analyses were performed to establish the significance of influence of different individual and coupled power tool-related parameters. The analysis of variance (ANOVA) results indicated that the vibration direction, acceleration and grip force influence the EMG of finger flexor muscles in a significant manner (P < 0.001), while the effect of vibration frequency was observed to be insignificant (P > 0.9). The electrical activity measured under different vibratory test conditions was observed to be 1.5-6.0 times higher than that measured under the static loads. The increase in electrical activity of the finger flexor muscles with an increase in the grip force was observed to be most significant under static as well as dynamic loading conditions. PMID- 7782124 TI - Assessment of long-term styrene exposure: a comparative study of a logbook method and biological monitoring. AB - In a recent joint European research project "Biomonitoring of human populations exposed to genotoxic environmental chemicals: biomonitoring of styrene exposed individuals", a logbook method for assessment of long-term styrene exposure was applied in two Danish factories manufacturing glass fibre-reinforced polyester. The method was based on work process identification, assignment of work process concentrations and logbook keeping. Measures of exposure calculated by this method were compared with results from simultaneous measurements of styrene in blood and the metabolites mandelic acid and phenylglyoxylic acid in urine. Correlations were comparable with those obtained by use of personal samplers as published in the literature. Styrene in blood, however, only correlated with logbook concentrations at the time of sampling. Exposures were moderate to low. Mean personal 8-h time-weighted average concentration (8hTWAC) was 76 mg/m3 styrene (SD 54 mg/m3, range 2-230 mg/m3). The Danish 8hTWAC threshold limit value for styrene in air, 105 mg/m3 (25 ppm), was exceeded on 17% of personal days. The summed urinary metabolites, mandelic acid and phenylglyoxylic acid, had a mean personal value of 138 mg/g creatinine (SD 84 mg/g creatinine) on the day of sampling. Blood styrene mean value was 129 micrograms/l (SD 74 micrograms/l, range 66-358 micrograms/l). It is concluded that the logbook method offers a technique for testing whether measurements are performed on representative days and may be recommended as a tool supplementary to biological monitoring in the assessment of long-term exposure. PMID- 7782125 TI - Immunological reactivity in ranitidine factory workers. AB - The involvement of immunological reactivity to ranitidine base (R-b) and ranitidine hydrochloride (R-HCl) in the development of occupationally related symptomatology was analyzed in 40 subjects employed in a pharmaceutical plant producing ranitidine and in 33 nonexposed controls, using a specific dose response lymphocyte proliferative test (lymphocyte transformation test: LTT). Of the 40 workers, 11 (28%) gave positive reactions to LTT: 3/11 to R-b, 4/11 to R HCl, and 4/11 to both compounds. None of the controls gave positive reactions. Cutaneous, oculonasal, or respiratory work-related symptoms were cited by 23 of the 40 (58%) subjects; ten of these 23 subjects (43%) were LTT positive. One asymptomatic case was LTT positive. The present results indicate that specific immune reactivity to ranitidine, analyzed by LTT, is associated with the presence of occupational symptomatology; R-HCl and R-b seem to share some antigenic determinants, because of the partial cross-reactivity shown by the examined compounds. Nonimmunological, probably irritative, mechanisms are also present in some of the symptomatic subjects. PMID- 7782126 TI - Evaluation of serum type III procollagen peptide as an exposure marker in retired coal workers. AB - Serum type III procollagen peptide (PIIIP), a degradation product of the type III collagen precursor, has been put forward as an exposure marker for mineral dust. We evaluated PIIIP levels as a marker of exposure to and effects of coal dust in retired coal miners (n = 104). To this end: (a) the individual cumulative dust exposure was calculated from job-exposure matrices, and (b) in addition to routine chest radiography (CR) of all miners according to the criteria of the International Labour Organisation (ILO), a subgroup (n = 46) was screened by high resolution computed tomography (HRCT). Profusion score (CR and HRCT) tended to increase with cumulative dust exposure, even in the absence of CR evidence for pneumoconiosis (i.e. CR < or = 0/1, n = 35). In contrast to our previous findings in active miners, PIIIP levels were not increased in miners as compared with non dust-exposed controls (n = 29), and no differences were observed between miners without (ILO = 0/0) and miners with coal workers' pneumoconiosis (CWP; ILO > or = 0/1). No trend in PIIIP versus pneumoconiosis stage was present, either by CR or by the more sensitive HRCT score. PIIIP was also unrelated to any lung function parameter (FEV1, FVC, impedance, diffusion capacity). Age, medication, medical history and smoking habits had no significant effect on PIIIP levels. In the miners with CWP (i.e. ILO > 0/0, n = 28) a significant negative correlation was present between PIIIP values and (log) cumulative dust exposure. This decrease in serum PIIIP levels with increasing cumulative exposure may be due to chronic adaptive changes in type III collagen deposition and/or breakdown. Other relations between exposure and PIIIP were not observed. In conclusion, the present findings do not support the use of serum type III procollagen peptide as a marker of exposure to and (early) interstitial or respiratory effects of coal dust. PMID- 7782128 TI - The role of lactate dehydrogenase-C4 in testicular function and infertility. PMID- 7782127 TI - Blood toluene as a biological index of environmental toluene exposure in the "normal" population and in occupationally exposed workers immediately after exposure and 16 hours later. AB - Blood toluene was measured in a group of 100 workers occupationally exposed to a mean 8-h environmental toluene concentration of 128 micrograms/l (34 ppm), and in a group of 269 "normal" subjects without occupational exposure to toluene. The mean blood toluene of the workers at the end of the shift and the following morning, after 16 h, was 457 and 38 micrograms/l, respectively. The normal subjects had a blood toluene level of 1.1 micrograms/l. On the basis of the highly significant correlation between blood toluene and occupational exposure, it can be calculated that environmental toluene exposure of 188 and 377 micrograms/l (50 and 100 ppm) gives end-of-shift blood toluene levels of 690 and 1390 micrograms/l, respectively. The corresponding blood toluene levels on the following morning are 50 and 100 micrograms/l, respectively. PMID- 7782129 TI - Myoid cell proliferation in rat seminiferous tubules after ischaemic testicular atrophy induced by epinephrine. Morphometric and immunohistochemical (bromo deoxyuridine and PCNA) studies. AB - The proliferation of peritubular myoid cells in the testes of rats treated for 1 11 weeks with intra-scrotal injections of epinephrine was investigated using immunohistochemistry and quantitative histology. The percentage of peritubular cells that were immunopositive for proliferating cell nuclear antigen (PCNA) or that were labelled with 5'-bromodeoxyuridine (BrdU) in the S-phase of the cell cycle, were calculated in control and treated rats after 1,3,5,8 and 11 weeks of treatment. In addition, the change in the number of peritubular cells per testis was calculated using two different stereological methods. The possible correlation between the changes observed using the two proliferation indices (PCNA immunoreaction and labelling of BrdU) in peritubular myoid cells was evaluated by regression analysis. The results of the study indicate that both proliferation indices increased in peritubular cells between the third and the eighth weeks of treatment, and that this increase was correlated with an increase in the number of these cells. From weeks 8-11 of treatment, both proliferation indices decreased and the same occurred with the number of peritubular cells. We hypothesize that proliferation of the peritubular cells occurs in order to increase their secretion of extracellular matrix components leading to enlargement of the lamina propria of the seminiferous tubule. PMID- 7782130 TI - Effect of seminiferous tubule size on hCG-induced regeneration of peritubular Leydig cells in hypophysectomized, EDS-treated rats. AB - Following their selective destruction 3 weeks previously by administration of ethane dimethanesulphonate (EDS) the regenerative capacity of Leydig cells was assessed in relation to seminiferous tubule morphology in hypophysectomized adult rats administered 7 daily injections of 100 iu hCG. Total Leydig cell volume per testis in hCG-treated rats (30.2 +/- 3.2 microliters, mean +/- SEM) was significantly (p < 0.01) greater than in the testes of rats at 3 and 4 weeks after EDS-treatment (7.6 +/- 0.7 and 22.7 +/- 1.4 microliters, respectively). Regeneration of Leydig cells in hCG-treated rats significantly (p < 0.05) favoured peritubular locations (18.6 +/- 2.8 microliters/testis) compared to central or perivascular sites of origin (11.6 +/- 1.2 microliters/testis). Partial restoration of spermatogenesis occurred in hCG-treated rats (tubule diameters usually > 250 microns) and a significant inverse correlation was found between peritubular Leydig cell percentage, or total volume per testis, and the volumetric proportion of seminiferous tubules (r = -0.94, p < 0.001) or the seminiferous epithelium (r = -0.73 to -0.79, p < 0.05-0.01). No significant (p > 0.4-0.9) correlation existed between centrally-regenerated Leydig cells and these parameters. The results show that in response to hCG stimulation, Leydig cells are more likely to develop around smaller seminiferous tubules, suggesting that hCG alone cannot mimic the expected pattern of Leydig cell regeneration (central and peritubular origins) which occurs during normal sexual maturation or at 3-4 weeks after EDS treatment. It is concluded that other factors, possibly FSH, are required for typical Leydig cell development which in turn may be influenced by local cellular growth factors originating from either the seminiferous tubules or the adjacent intertubular tissue. PMID- 7782131 TI - Temporal changes in sulphated glycoprotein-2 (clusterin) and ornithine decarboxylase mRNA levels in the rat testis after ethane-dimethane sulphonate induced degeneration of Leydig cells. AB - Short- (3-24 h) and long-term (4-50 days) changes in sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC) mRNA levels in the adult rat testis were studied following a single dose of ethane-dimethane sulphonate (EDS), to destroy the Leydig cells. Distribution patterns of SGP-2 and ODC labelling were consistent with prevailing expression of the two transcripts in Sertoli cells and germ cells, respectively. This pattern did not show appreciable changes following EDS administration. No labelling of SGP-2 mRNA was noted in the interstitium of control and EDS-treated rats. This finding indicates that Leydig cell death induced by EDS is not associated with increased SGP-2 mRNA levels, a phenomenon related to apoptotic cell death in many tissues. Semi-quantitative densitometric analysis of the preparations demonstrated differential changes in SGP-2 and ODC mRNA levels in the tubular compartment following EDS treatment. At 6, but not at 3 and 12, h following EDS administration, SGP-2 mRNA levels showed a significant increase, possibly secondary to a direct effect of the alkylating agent on Sertoli cells. A significant decrease in ODC mRNA levels was observed from day 7 to day 28, matching degenerative changes in the seminiferous epithelium. In contrast, a decrease in SGP-2 transcript levels was observed from days 21-35 after treatment. In conclusion, our findings demonstrate that SGP-2 mRNA, a putative marker of apoptosis, is not altered in the testicular interstitium during EDS-induced degeneration of Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782132 TI - Insulin-like growth factor-I and transforming growth factor-alpha stimulate differentiation of type A spermatogonia in organ culture of adult mouse cryptorchid testes. AB - This study assessed the effect of growth factors on testicular germ cell differentiation in vitro. Testicular fragments of experimentally prepared cryptorchid testes of adult mice were cultured for 9 days in serum-free media containing various concentrations of IGF-I, TGF-alpha, FGF, and PDGF. Their histology was then examined under a light microscope. Each type of germ cell and mitotic cell in the seminiferous tubules was counted per 1000 Sertoli cells. IGF I at a concentration of 10 ng/ml induced maximal differentiation of type A spermatogonia. TGF-alpha at concentrations ranging from 1 to 10 ng/ml also stimulated differentiation, whereas FGF and PDGF did not show any stimulation of spermatogonial differentiation in this experimental system. PMID- 7782133 TI - Amiodarone effects on membrane organization evaluated by fluorescence polarization. AB - The effects of amiodarone (0-100 microM) on the physical state of synthetic and native membranes were investigated by fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene (DPH), probing the bilayer core, and of its anionic propionic acid derivative (DPH-PA), probing the outer regions of the bilayer. In the gel phase of dimyristoylphosphatidylcholine (DMPC) bilayers, amiodarone broadens the transition profile and shifts the phase transition midpoint to lower temperature values, as evaluated by both probes. On the other hand, the drug orders the fluid phase of the lipid either in hydrophobic core or in the outer regions of the bilayer, as detected by DPH and DPH-PA, respectively. The effects of amiodarone on the thermotropic behaviour of DPPC confirm and extend data in DMPC. Cholesterol concentration modulates to a great extent the effects of amiodarone in the fluid phase of DMPC. Thus, both probes, DPH and DPH-PA, detect either ordering effects of amiodarone for low cholesterol concentrations (< or = 20 mol%) or disordering amiodarone effects at higher cholesterol levels (> 20 mol%). In agreement with the results in models of synthetic lipids, the ordering effects of amiodarone in fluid native membranes of mitochondria and brain microsomes are depressed with the increase in intrinsic cholesterol. The ordering effects in mitochondria may induce bioenergetic dysfunctions and consequently disturbances in the electromechanic functioning of myocardium. PMID- 7782134 TI - Recombinant tissue-type plasminogen activator therapy in prosthetic mitral valve thrombosis: assessment by transthoracic and transesophageal echocardiography. AB - Prosthetic cardiac thrombosis is a life-threatening complication that needs prompt diagnosis and therapy. We used recombinant tissue-type plasminogen activator (rT-PA), followed by heparin, in three patients with mitral prosthetic thrombosis, which was evident in two and suspect in one. Transthoracic and transesophageal echocardiography were employed in the diagnosis of both thrombosis and its resolution. No complications occurred. Immediately after the end of treatment with rT-PA, clinical status and echocardiographic data improved in all cases: transthoracic echocardiography showed the normalization of prosthetic function and transesophageal echocardiography showed resolution of thrombosis. One patient needed reoperation for rethrombosis due to the presence of prosthetic fibrous clot. rT-PA, followed by heparin, led to a good clinical result without bleeding and embolic complications in selected patients with mitral prosthetic thrombosis. Transthoracic and transesophageal echocardiography are complementary diagnostic tools in the diagnosis and management of patients with prosthetic thrombosis. PMID- 7782135 TI - Surgical treatment of complete atrioventricular septal defect associated with tetralogy of Fallot. AB - The combination of complete atrioventricular septal defect (AVSD) and tetralogy of Fallot (TF) was reported to occur in less than 2% of patients undergoing repair of TF. From September 1981 to November 1989, five consecutive patients with such combination underwent total correction at National Taiwan University Hospital. Their age ranged from 3.8 years to 6.3 years. Two cases were associated with Down's syndrome. All interventricular communications were repaired by combined transatrial and transventricular approach and a separate pericardial patch was used to repair the interatrial communication. The transannular patch (TAP) was not used in one case; of the four cases with TAP, a pericardial monocusp was mounted in one of them. There was one hospital mortality, and one late death. Both were related to intractable right heart failure. We conclude that total repair of this anomaly could be accomplished after 3 years of age provided there is thorough awareness of anatomical features and avoidance of right heart failure. PMID- 7782136 TI - Influence of percutaneous transluminal coronary angioplasty on cardiac release of endothelin, neuropeptide Y and noradrenaline. AB - In the present study, the cardiac outflow of endothelin, noradrenaline and neuropeptide Y was investigated in 13 patients undergoing first time coronary angioplasty (PTCA) due to stenosis of the left anterior descending coronary artery. During PTCA there was an increase in the coronary sinus levels of endothelin but no detectable changes in neuropeptide Y or noradrenaline concentrations. It is therefore concluded that endothelial damage rather than myocardial ischaemia is the cause of endothelin release during PTCA. PMID- 7782137 TI - Mortality and clinical course of patients with acute myocardial infarction treated with streptokinase and antioxidants: mannitol and ascorbic acid. AB - There is increasing evidence that free radical scavengers limit reperfusion injury in animal experiments. We randomly administered 250 ml 20% mannitol infusion and 10.0 g ascorbic acid infusion, potent free radical scavengers to 42 patients with acute myocardial infarction receiving streptokinase. A control group of 42 patients received only standard fibrinolytic therapy. We found that additional antioxidant treatment with ascorbic acid and mannitol decreased the number of some complications of acute myocardial infarction. PMID- 7782139 TI - Biochemical diagnosis of myocardial infarction within the thrombolytic time window. AB - A demonstrated temporal change in the total activity of creatine kinase or mass measurement of the cardio-specific isoenzyme creatine kinase MB is currently used as the biochemical diagnosis of myocardial infarction. The isoforms of creatine kinase MB may provide an earlier diagnostic marker of myocardial infarction than the currently available biochemical markers. We compare the sensitivity and specificity of total creatine kinase activity, creatine kinase MB mass measurement and the muscle and heart specific isoforms of creatine kinase in the early diagnosis of myocardial infarction. Using current methodologies, neither CK isoform offered any advantage over CK mass measurement as an early marker of ischaemic myocardial damage. PMID- 7782138 TI - The value of exercise electrocardiography testing in the identification of coronary restenosis: a probability analysis. AB - We studied by means of probability analysis the role of exercise ECG in identifying coronary restenosis. A total of 213 patients were independently evaluated by clinical history, conventional assessment of the exercise ECG ('yes or no' statement), D score (a discriminant function derived from exercise ECG), and coronariography, 5.4 +/- 2.8 months after successful coronary angioplasty. The initial probability of restenosis (30%), that is, the prevalence of the condition, was radically changed by the result of clinical history (77% for patients with angina vs. 17% for those without angina). By contrast, ECG binary assessment, due to its low accuracy (70% vs 82% of clinical history, P < 0.005), was unable to significantly change the established probabilities after symptomatic evaluation. Finally, D score, which greatly enhanced specificity (92% vs. 76% of bivariate assessment, P < 0.0001), proved to be useful in changing the probability (from 32% to 76% or to 25%) of patients (n = 34) with a discordant result (no angina/positive exercise ECG). When this stepwise approach was tested in 46 new patients, predicted and observed probabilities were actually very similar. We conclude that exercise ECG has a very limited role in identifying coronary restenosis if positive responses are not adjusted with a weighted score which takes into account other exercise derived factors. PMID- 7782140 TI - Effect of verapamil on the prognosis of patients with early postinfarction electrical or mechanical complications. The Danish Verapamil Infarction Trial II (DAVIT II). AB - The Danish Verapamil Infarction Trial II (DAVIT II) demonstrated from the second postinfarction week, that long term treatment with verapamil significantly improved reinfarction free survival after an acute myocardial infarction (AMI). The present post hoc analysis of DAVIT II was undertaken with the purpose of evaluating the effect of treatment with verapamil in patients with early electrical complications, i.e. ventricular or atrial fibrillation, ventricular tachycardia, or second or third degree atrioventricular block, with or without mechanical complication, i.e. heart failure, during the first post-AMI week. In the placebo group, the 18-month mortality rate was lowest (9.5%) in patients without electrical or mechanical complications, highest (24.6%) in patients with electrical events only, and in-between (17.5%) in patients with mechanical problems regardless of presence of electrical complications. Verapamil significantly reduced the 18-month mortality rate in patients with early electrical without mechanical complications (60% reduction, P = 0.02), and in patients without mechanical complications (35% reduction, P = 0.02). Verapamil did not change the mortality rate in patients with mechanical complications. PMID- 7782141 TI - Ventilation-perfusion matching in chronic heart failure. AB - BACKGROUND: The exercise limitation of patients with chronic heart failure is associated with an increased ventilatory response during exercise. This is thought to be due, at least in part, to excessive dead space ventilation. METHODS: To assess ventilation perfusion matching, 20 patients with chronic heart failure and eight controls with asymptomatic left ventricular dysfunction underwent symptom limited treadmill exercise with arterial blood sampling. Metabolic gas exchange was determined by expired gas analysis. Fractional dead space ventilation and the alveolar arterial oxygen difference were derived. RESULTS: There was a fall in fractional dead space ventilation (0.43 to 0.28; P < 0.001), more marked in the controls (peak dead space fraction 0.19 (controls), 0.32 (patients); P = 0.002). There was a rise in alveolar arterial difference in all patients (1.59 to 2.55 kPa; P = 0.006) with no difference between patients and controls. Arterial carbon dioxide tension fell during exercise (4.89 to 4.63 kPa; P < 0.001), with no difference between patients and controls. There was no significant change in arterial oxygen tension. CONCLUSIONS: The fall in arterial carbon dioxide was the same in both patients and controls. The modest increase in alveolar-arterial oxygen difference tension was the same in both groups, which, coupled with the stable arterial oxygen tension makes it unlikely that a primary change in ventilation-perfusion matching is the cause of increased ventilatory response to exercise in chronic heart failure. PMID- 7782142 TI - Presentation and management of patients admitted with atrial fibrillation: a review of 291 cases in a regional hospital. AB - Two hundred and ninety one patients admitted with atrial fibrillation through the emergency room of a regional hospital in the year 1993 were reviewed to evaluate the presenting features and in-hospital treatment of patients with symptomatic atrial fibrillation. The incidence of atrial fibrillation increased with age (mean age was 73 +/- 12 years) and the ratio of female to male was 1.8:1. The commonest presenting features were palpitation (42.3%), dyspnoea (38.1%) and heart failure (16.4%). The most frequently associated cardiac conditions were hypertension (28.9%), atherosclerotic cardiovascular disease (24.7%) and rheumatic heart disease (17.5%). Pulmonary diseases (18.6%), diabetes mellitus (12.7%) and thyrotoxicosis (6.2%) were the principal associated non-cardiac conditions. Thromboembolic complications were found in 15 patients at presentation (5.2%). Cardiac enzyme assessment was investigated in two thirds of the patients (68.1%), while thyroid function test (59.5%) and echocardiography (29.6%) were less commonly investigated. Digoxin was still the most popular drug used for ventricular rate control, and cardioversion was performed in only 6.9% of patients. Antithrombotic therapy was used in 5.8% of patients only although it was clinically indicated in more than half of the patients (52%). Contraindications of anticoagulation were found in 23 patients (7.9%), including a history of gastrointestinal or cerebrovascular bleeding, active bleeding, chronic renal failure and poor drug compliance. The mean hospital stay was 5 +/- 4 days, compared to a mean stay of 2.7 days for other medical patients. Fourteen patients (4.8%) died during hospitalisation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782143 TI - The effects of sympathetic stimulation induced by mental stress on signal averaged electrocardiogram. AB - We evaluated the influence of sympathetic stimulation, induced by mental stress test, on signal-averaged ECG in 30 healthy subjects and in 30 patients with previous myocardial infarction. Both patient and control groups underwent three consecutive signal-averaged ECG: under basal conditions, during a continuous mental stress test, and 5 min after the mental stress test. The signal-averaged ECG parameters, analyzed by mean of a bandpass filter of 25-250 and 40-250 Hz, were: the filtered QRS duration, the duration of the low-amplitude high frequency signals in the terminal portions of the QRS complex below 40 microV (HFLA), and the root mean square voltage in the last 40 ms of the filtered QRS (RMS). The mathematical stress test was considered effective when the heart rate increased by at least 15 beats/min, remaining stable for the total duration of the signal averaged ECG acquisition. A significant reduction of the filtered QRS duration and HFLA with a simultaneous increase of RMS were found in control group, while no significant changes occurred in patient group. These results indicate that the sympathetic nervous system may affect the results of signal-averaged ECG, probably by influences on intraventricular conduction, in healthy subjects. On the contrary, myocardial alterations in ischemic heart disease induce modification of signal-averaged ECG not influenced by autonomic nervous system activity. PMID- 7782144 TI - Dietary fat purchasing habits in whites, blacks and Asian peoples in England- implications for heart disease prevention. AB - The mortality and morbidity from coronary heart disease (CHD) is higher in people of South Asian origin than in whites, but is significantly lower in the black (Afro-Caribbean origin) community in the United Kingdom. To investigate whether this may be related to differences in fatty food intake, we performed a questionnaire survey of the weekly food purchasing habits and preparation methods in white, black (Caribbean) and Asian households in Birmingham. We interviewed 224 housewives from three ethnic groups (84 white, 76 black/Afro-Caribbean and 72 Asian). The highest quantity of fat in foods purchased per week was found in the Asian population (median 1409 g/week per person, interquartile range (IQR) 850 1952), which was significantly greater than black subjects, who had the lowest quantity of fat in foods purchased (1012 g/week per person, IQR 835-1388) (Mann Whitney test:median differences 300.5, 95% C.I. 23.3-600.4, P = 0.029). The median quantity of fat in foods purchased by the white households was intermediate, at 1186 g/week per person (IQR 861-1711). There was a higher quantity of fat in foods purchased in the lower social classes (IV and V) in both the white and Asian populations. Butter, egg and milk consumption was significantly greater in Asians; with ghee consumption almost exclusive amongst this group (98%). Amongst whites and blacks, the commonest food preparation methods were grilling, boiling or poaching; whilst amongst Asians, frying was more common (chi 2 = 81.25, d.f. = 4, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782145 TI - General practitioners' requirements from a hospital cardiology department. AB - The requirements of 500 general practitioners from a hospital department of cardiology were sought and assessed from a questionnaire. One hundred and twenty two general practitioners caring for 766,384 patients responded. The most important inpatient service requirement was that cardiologists should be responsible for the management of patients with acute myocardial infarction and other acute cardiac conditions. The expertise and reputation of the consultant cardiologist and the waiting time for an appointment were the two most important outpatient service requirements. The least important aspect was the time patients waited in clinic to see a doctor. Fundholders considered price of outpatient consultations to be unimportant. Waiting times for cardiac catheterisation and non-invasive cardiac investigations together with the quality of the investigation equipment and the technical staff were all considered to be important requirements. Most general practitioners wanted protocols for managing common cardiac conditions. The majority wanted an open access investigation service to reduce outpatient waiting times. Those who did not want an open access service explained that they would not be confident in interpreting the results or deciding subsequent management. An understanding of the requirements of general practitioners is helpful in planning and developing hospital services. PMID- 7782146 TI - Blood pressure response to stress tests does not reflect blood pressure variability and degree of cardiovascular involvement in young hypertensives. AB - The aim of the study was to assess the clinical value of blood pressure response to stress tests and to study its relationship with ambulatory blood pressure monitoring, daily blood pressure variability and hypertensive complications. Cold pressor test for 2 min, hand grip test at 25% of maximal voluntary contraction for 5 min and orthostatism were performed in 223 young men found hypertensive (BP systolic > 140 mmHg and/or diastolic > 90 mmHg) at the military service recruitment check-up. On the basis of ECG and fundoscopic examination, each patient was attributed a score of target organ damage. All patients underwent non invasive 24-h blood pressure monitoring and 169 patients underwent echocardiographic examination. Hypertension was confirmed in 54.2% of the subjects at ambulatory monitoring. No correlation was found between blood pressure response to stress tests and ambulatory blood pressure, daily blood pressure variability, target organ damage and left ventricular mass. Night-time ambulatory blood pressure were correlated with posterior wall thickness/ventricular diastolic internal diameter ratio (r = 0.26, P < 0.001). A negative correlation was found between the office-daytime blood pressure difference and systolic and diastolic response to orthostatic test (r = -0.309, P < 0.0001 for systolic blood pressure and r = -0.433, P < 0.0001 for diastolic blood pressure) and between supine office blood pressure and blood pressure response to orthostatism (r = -0.186. P = 0.013 for systolic blood pressure and r = -0.442, P < 0.0001 for diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782147 TI - Influence of isolated diastolic hypertension identified by ambulatory blood pressure on target organ damage. AB - Clinical decisions and controlled studies in regard to hypertension have long emphasized the casual diastolic blood pressure (DBP). The influence of superimposition of high systolic blood pressure (SBP) on the target organ damage has been less studied. To assess the role of isolated diastolic hypertension without interference of superimposition of systolic hypertension, 171 subjects with normal blood pressure, isolated diastolic hypertension (SBP < 140 and DBP > or = 90 mmHg) isolated systolic hypertension (SBP > or = 140 and DBP < 90 mmHg) or combined hypertension (SBP > or = 140 and DBP > or = 90 mmHg) determined by mean 24-h ambulatory blood pressure were compared in relation to target organ damage including ECG abnormality related to hypertension, cardiac enlargement by chest X-ray, proteinuria and retinopathy. The incidence of target organ damage was lower in subjects with normal BP than in the other three groups. The incidence of target organ damage was almost significantly higher in patients with isolated systolic hypertension than in those with isolated diastolic hypertension. No significant difference in the incidence of complications existed between patients with isolated systolic and combined hypertension. These findings demonstrate that the severity of hypertensive complications is more closely related to mean ambulatory SBP than mean ambulatory DBP. The level of systolic BP is important for predicting the severity of target organ damage in patients with high diastolic BP, because there is a significant difference in the incidence of target organ damage between isolated diastolic hypertension and combined hypertension. PMID- 7782148 TI - Cardiomyopathic lentiginosis: an echo-Doppler report. AB - We report a case of a 64-year-old woman with cardiomyopathic lentiginosis. All the echocardiographic features of a hypertrophic obstructive cardiomyopathy were detected, with an accurate noninvasive measure of the left ventricle outflow gradient. PMID- 7782149 TI - Effect of cisplatin and FK565 on the activation of tumor-associated and bone marrow-derived macrophages by Dalton's lymphoma. AB - The present investigations were undertaken to study the effect of Dalton's lymphoma (DL) in situ on the functions of DL-associated macrophages (DL-AM) and bone marrow-derived macrophages (BMDM) in C3H/He mice. DL-AM showed enhanced production of reactive nitrogen intermediates (RNI) and tumor necrosis factor (TNF) compared with normal peritoneal macrophages (NMO). BMDM of DL mice also showed enhanced production of RNI compared with BMDM of normal mice. These observations suggest that the presence of DL in situ creates an environment which favours the activation of both DL-AM and macrophage progenitors located at a distant site. The effect of in vivo administration of chemotherapeutic drugs cisplatin and FK565 on the activation of DL-AM by DL cells was also investigated. Both cisplatin and FK565 augmented RNI production of NMO but differed in their effect on DL-AM. The production of RNI by DL-AM of cisplatin-treated mice was inhibited, whereas in the FK565 group it was up-regulated. PMID- 7782150 TI - Effects of triiodothyronine supplements on splenic natural killer cells in malnourished weanling mice. AB - The main purpose of this investigation was to determine whether exogenous triiodothyronine (T3) administered according to a protocol known to prevent depression in acquired immunity in weanling murine protein-energy malnutrition (PEM) would, likewise, influence the splenic natural killer (NK) cell in this disease. Weanling mice of disparate inbred strains, C57BL/6J and CBA/J, were subjected to wasting PEM produced by means of two low-protein diets (0.5% crude protein) identical in every respect except that one diet contained supplemental T3 (0.2 micrograms/g diet). NK cell lytic activity toward YAC-1 targets was assessed in vitro using suspensions containing 0.5 x 10(6) mononuclear spleen cells. Lytic activity in this assay was low in mice fed the unsupplemented low protein diet, but was not depressed in malnourished animals given exogenous T3. Surface marker analysis using the NK cell-specific antigen, NK 1.1 (PK 136), revealed no effect of the low-protein diet or of exogenous T3 on the proportion of splenic mononuclear cells exhibiting NK 1.1+ phenotype. Previous investigations have shown that acquired immune competence in PEM can be manipulated, by means of endocrine hormonal intervention, independently of continued wasting disease. The present results extend this fundamental new concept to include an innate immune function, namely NK cell lytic activity. In this system of experimental PEM, exogenous T3 prevented depression in NK cell lytic activity expressed on a per cell basis. The malnourished weanling rodent is a particularly powerful experimental system with which to investigate the mechanisms whereby thyroid hormones influence NK cells. PMID- 7782151 TI - Accelerated myelopoietic recovery in irradiated mice treated with Photofrin. AB - The porphyrin photosensitizer, Photofrin porfimer sodium (Photofrin), has been widely studied for its capacity to evoke destruction of malignant tissues. In addition to its photosensitizing properties, Photofrin may exert myelostimulatory effects in normal and immunosuppressed mice in the absence of activating light. In the present set of experiments, we examined the effect of Photofrin upon the immunohematopoietic axis of sublethally irradiated DBA/2 mice. Administration of Photofrin (10 mg/kg) 1 and 4 days following irradiation (4 Gy) significantly enhanced the recovery of spleen cellularity, spleen and bone granulocyte/macrophage progenitors (colony-forming units, CFU-GM) and peripheral blood leukocytes levels. Proliferative responses to the T-cell mitogen concanavalin A by spleen cells prepared from Photofrin-treated mice were significantly less than those of cells from irradiated control mice 8 and 15 days post-irradiation. Photofrin given 1, 4 and 7 days following irradiation elevated splenic CFU-GM 3 to 4-fold 10 days post-irradiation relative to the irradiated controls and mice given only two injections of Photofrin. In contrast to the effect of two injections, multiple (three or four) injections of Photofrin did not elevate bone marrow CFU-GM above control levels beyond 8 days post irradiation. In addition, splenic CFU-GM levels in animals receiving three or four injections of Photofrin were no different than those of the irradiated controls later than 10 days post-irradiation. These findings indicate that prolonged exposure to Photofrin in sublethally irradiated mice may induce regulatory factors which dampen the enhanced myelopoietic recovery stimulated by only two injections of the drug. PMID- 7782153 TI - In vivo and in vitro effects of macrophage colony-stimulating factor (M-CSF) on bronchoalveolar macrophages for antihistoplasmal activity. AB - The in vivo and in vitro effects of M-CSF on bronchoalveolar macrophages (BAM) activity against the intracellular fungal pathogen Histoplasma capsulatum (Hc) were studied. Three days after a single subcutaneous (s.c.) dose of M-CSF (2.5 mg/kg), enhanced ex vivo antifungal activity of BAM was measured. BAM from M-CSF treated CD-1 mice significantly (P < 0.01) inhibited the intracellular multiplication of Hc yeast cells in 20 h assays compared to BAM from control mice. This effect was not observed at days 1, 7, 11 or 21 post-treatment. A dose of 5 mg/kg s.c., but not 1 mg/kg, induced similar antifungal activity in BAM by day 3. Peritoneal macrophages (PM) from M-CSF-treated mice did not have enhanced antifungal activity at days and doses tested. BAM could also be activated for antihistoplasmal activity by M-CSF in vitro. M-CSF at 10,000 U/ml for 24 h or 5000 U/ml for 48 h induced significant (P < 0.01) inhibition of intracellular multiplication of Hc. Interferon-gamma (IFN) plus lipopolysaccharide (LPS) activated BAM and PM in vitro to inhibit intracellular multiplication of Hc (P < 0.001); the antihistoplasmal activity was completely inhibited by NG-monomethyl L arginine (N-MMA), indicating that an L-arginine-dependent nitric oxide-producing mechanism was operative. N-MMA could not inhibit the antihistoplasmal activity of BAM or PM activated by M-CSF in vitro. The mechanism by which M-CSF-activated macrophages inhibit intracellular multiplication of Hc remains to be determined. PMID- 7782152 TI - Immunomodulating IL-6 activity by murine monoclonal antibodies. AB - The human anti-mouse immunoglobulin antibody (HAMA) response, which occurs frequently after injection of murine monoclonal antibodies (MAb) directed against cellular targets, has been reported extensively in several studies. We analysed here HAMA in 12 patients (six with multiple myeloma, MM, and six with metastatic renal cell carcinoma, MRCC) who were treated with B-E8, an IgG1 MAb against interleukin-6 (IL-6). Efficiency of the treatment was evidenced by the drop in the serum levels of C reactive protein (CRP), of which the in vivo production is under the control of IL-6. Three patients with MM and the six patients with MRCC became immunized to the injected MAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies; four also made IgM. All of immunized patients made anti-idiotype antibodies specific to B E8. Two of them also developed HAMA directed to murine IgG1 isotype; in these two patients B-E8 MAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti-idiotype antibodies, serum levels of B-E8 remained unchanged and CRP production remained inhibited, indicating that treatment efficiency was not affected by the presence of HAMA. Circulating B-E8 MAb were still able to bind to IL-6 and to inhibit IL-6 independent proliferation despite the presence of anti-idiotypic HAMA. Therefore, in contrast to HAMA against MAb directed against cellular targets, HAMA against anti-IL-6 MAb idiotopes led neither to clearance nor to functional inactivation of the injected MAb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782154 TI - Stimulatory effects of cocaine and its metabolites on IM-9 human B-lymphoblastoid cells. AB - This study examined the effect of cocaine and its metabolites benzoylecgonine, norcocaine, and cocaethylene on human B-cell proliferation using IM-9 cells. Cells were incubated with 0.01-10 micrograms/ml of cocaine or metabolite in serum free medium or medium containing 2% FBS for 24 and 48 h, and [3H] thymidine incorporation into DNA was measured using liquid scintillation counting. Results showed incubation with cocaine and metabolites significantly increased IM-9 cell proliferation. With cocaine, maximal stimulation of 148% (compared to drug-free control) occurred at 1.0 micrograms/ml in serum-free medium at 48 h. Benzoylecgonine and norcocaine showed maximal stimulation at 0.1 micrograms/ml with 170% and 150% stimulation, respectively. Cocaethylene showed maximal stimulation of 146% at 10 micrograms/ml. Drug stability was monitored under incubation conditions using high-performance liquid chromatography (HPLC). We have shown that cocaine and its major metabolites have an immunomodulatory effect on B-cell proliferation at concentrations equivalent to serum levels produced during cocaine use in humans. Since the cocaine metabolites also show an immunomodulatory effect, the immune consequences of cocaine use may be significantly prolonged. PMID- 7782155 TI - Liposomal adjuvanticity: effect of encapsulation and surface-linkage on antibody production and proliferative response. AB - The immunoadjuvanticity of liposomal antigens, namely encapsulated and surface linked conalbumin, was studied at different levels of an immune response including immunoglobulin production, blastogenic response and lymphokine production in sensitization conditions compatible with vaccine designs. The results demonstrated that both liposomal formulations stimulate all properties analyzed with respect to free antigen but significantly differ in some of their inductive capabilities, suggesting that they follow different routes in the immune network. Thus, although both liposomal antigens are capable of inducing potent humoral responses characterized by increased production of IgM and IgG2a, covalently linked antigen stimulates a quasi-polyclonal blastogenic response accompanied by the simultaneous secretion of IL-2 and IFN gamma, while encapsulated antigen which is less blastogenic mainly induces IL-2 secretion. We can conclude that: first, both antigenic formulations induce a Th1 type of activation and might therefore potentiate cell-mediated immunity, but surface linkage favors a more rapid maturation of the response and a much more intense help induction. Second, although a strong adjuvanticity can be observed whatever the route of sensitization, namely intraperitoneally, intravenously or subcutaneously, the intravenous injections induce the better potentiation. The in vitro data were all compared to those obtained with naive mice, allowing dissociation of the contribution of the in vitro rechallenge from that of the in vivo immunization. These differences observed between the liposomal antigens might be taken advantage of while formulating vaccines specifically suited to meet required needs and suggest that covalently linked antigen might be particularly useful in situations where induction of cell-mediated immunity is of prime importance. PMID- 7782156 TI - Conformation and structure of linear peptides with regularly alternating L- and D residues: structure of the blocked hexapeptide tert-butyloxycarbonyl-(D alloisoleucyl-L-isoleucyl)3 methyl ester monohydrate. AB - Peptides with a regular sequence of enantiomeric residues (L and D) along the chain have received considerable attention because of their accessibility to unique conformations and because they are model compounds for the naturally occurring peptide gramicidin A, which shows monovalent cation selective transmembrane transport. The solid-state structure of the linear hexapeptide t Boc-(D-alle-L-Ile)3-OMe has been determined by X-ray diffraction techniques and refined to a final R factor of 0.068. The molecule shows a bent U-shaped conformation stabilized by three intramolecular H-bonds of the N-H...O = C type: a type II beta-bend (4-->1 bend or C10 ring structure) with L-Ile2 and D-aIle3 at positions 2 and 3 of the bend, an alpha-turn (5-->1 bend or C13 ring structure) and a 1-->5 bend or C17 ring structure. The first two 10-membered and 13-membered bends are enclosed in the latter 17-membered hydrogen-bonded ring structure. This structural motif is common to hepta- and octa-peptide cyclic molecules, showing that ring closure is not required to achieve a particular topology in the molecular design of specific bended conformations. PMID- 7782157 TI - Synthesis of alpha-factor analogues containing photoactivatable and labeling groups. AB - Analogues of alpha-factor, Saccharomyces cerevisiae tridecapeptide mating pheromone (H-Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr-OH), containing both p-benzoyl phenylalanine (Bpa), a photoactivatable group, and 3-(mono- or di iodo-4-hydroxyphenyl)propanoic acid (iodinated HPP) or biotin as a tag, were synthesized using solid-phase methodologies on a [phenylacetamido]-methyl (PAM) resin. Bpa was introduced into the peptides using Bpa-hydroxybenzotriazole active ester during peptide chain assembly. Biotinylated alpha-factor analogues were prepared by assembling the desired peptide on the resin, and then reacting a specific amino group either with the symmetrical anhydride of biotin or with biotin using BOP as the activating agent prior to anhydrous hydrogen fluoride cleavage. Iodinated HPP was incorporated by acylating free peptides with Bolton Hunter reagent (3-[diiodo-4-hydroxyphenyl]propanoic acid hydroxysuccinimide ester) in N,N-dimethylformamide and borate buffer (pH 8.0) solutions. Purification of all peptides to 98% or greater homogeneity was accomplished by high-performance liquid chromatography on a reversed-phase mu-Bondapak C18 column with acetonitrile/water/trifluoroacetic acid as the mobile phase. All products were characterized by amino acid analysis and fast atom bombardment mass spectrometry. Two analogues, alpha-(diiodotyrosine)-His-Bpa-Leu-Gln-Leu-Arg-Pro Gly-Gln-Pro-Nle-Tyr-O H, and epsilon-(diiodo-HPP)-Lys-His-Bpa-Leu-Gln-Leu-Arg-Pro Gly-Gln-Pro-Nle-Tyr -OH, were one twentieth to one-fortieth as active as a alpha factor, and exhibited approximately one order of magnitude lower affinity to the alpha-factor receptor. The results suggest that these two analogues are alpha factor agonists and that they can be used as probes of the alpha-factor receptor. PMID- 7782158 TI - The 2,4-dinitrophenyl group for protection of hydroxyl function of tyrosine during solid-phase peptide synthesis. AB - The facile thiolytic cleavage of the O-2,4-dinitrophenyl (Dnp) tyrosine bound was applied to the solid-phase synthesis of the 22-amino acid residue peptide H-Asp Ala-Val-Tyr-Thr-Gly-Leu-Asn-Thr-Arg-Asn-Gln-Glu-Thr-Tyr-Glu-Thr-Le u-Lys- His-Glu Lys-OH, corresponding to positions 62-83 in the chain of the type 1 receptor for Fc epsilon domains expressed on the rat mucosal-type mast cells (line RBL-2H3). A method for the spectrophotometric determination of insoluble O-Dnp as well as of unprotected phenolic moieties of tyrosine was developed. It is based on monitoring S-Dnp-2-mercaptoethanol, produced upon O-Dnp thiolysis by 2 mercaptoethanol. PMID- 7782159 TI - Mechanism of solvent-induced thermal stabilization of alpha-amylase from Bacillus amyloliquefaciens. AB - The transition temperature of irreversible thermal inactivation of alpha-amylase from Bacillus amyloliquefaciens was estimated to be 60 degrees C. At this temperature, the enzyme inactivation followed first-order kinetics, having a half life (t 1/2) of 12 min with a rate constant (k) of 0.06 min-1. Conformational change was a prerequisite for this thermal inactivation. This is governed by stepwise temperature-dependent phenomena. Among the solvent stabilizers tested, the enzyme was thermally stable in presence of DMSO and PEG 300 and the stabilizing efficiency of these cosolvents was concentration-dependent. The enzyme was partially stabilized by 5.0 M DMSO and 1.9 M PEG 300 up to 78 degrees C. However, above 78 degrees C the enzyme was inactivated in these cosolvents also. The mechanism of stabilization has been explained by preferential hydration of the enzyme in these structure stabilizing solvents by exclusion from the protein surface and interface by measurement of partial specific volume in these cosolvents. The data suggest a high value of preferential interaction parameter, (delta g3/delta g2)tau, mu 1, mu 3 being -0.606/g/g g/g in 40% DMSO and a low value of -0.025 g/g in 5% glycerol. The preferential interaction parameters in sucrose and glycerol suggests that (delta g3/delta g2)tau, mu 1, mu 3m is highest of -0.420 g/g in 10% glycerol than any other cosolvent. PMID- 7782160 TI - Peptide aggregates: a novel model system to study self-assembly of peptides. AB - Ordered aggregates of Val-Leu-Pro-Phe, tetrapeptide 1, have been found in aqueous solutions. Evidence for the formation of aggregates for the above peptide was obtained by conductometric, pH metric, UV and fluorescence spectroscopic techniques. Values of critical micelle concentration (CMC) for the above peptide obtained by these methods are in good agreement with each other. The formation of organized aggregates of the peptide is favoured upon increasing the temperature (viz. the process of aggregation is endothermic). The aggregation number has been determined at different temperatures. Values of delta G0m, delta H0m, delta S0m and delta C0p have also been estimated. Binding studies with the 8 anilinonaphthyl sulfonic acid (ANS) and pyrene indicate that the interior of the aggregate is nonpolar. There are two processes with regard to the change of thermodynamical parameters like delta G0m, delta H0m, delta S0m, delta C0p and aggregation number (N). In the first process (from 5 degrees C to 40 degrees C) the driving force for aggregation seems to be the positive entropy because of water release due to intermolecular association of ionic moieties. The second process (from 40 degrees C and above) is due to intramolecular ionic interaction. The chemical shifts of the amide protons of the peptide have been presented in the light of inter- and intramolecular hydrogen-bond formation, and forces implicated in aggregation for both the first and second processes. PMID- 7782161 TI - Incorporation of thioamide linkages into a growing peptide under SPPS conditions improved by salt effects. AB - Amino acid methyl dithioesters may be coupled in the presence of DMAP and salts to a growing peptide chain on a polymeric resin with high coupling yields and low racemization. PMID- 7782162 TI - 'Tethered ligand' derived pentapeptide agonists of thrombin receptor: a study of side chain requirements for human platelet activation and GTPase stimulation. AB - Proteolytic action of alpha-thrombin on human thrombin receptor results in cleavage of a portion of the N-terminus, thereby generating a 'tethered ligand' at the newly exposed N-terminus, which then activates the receptor in an intramolecular fashion. Agonist peptides incorporating the amino acid sequence of the newly exposed N-terminal portion of the cleaved receptor cause receptor activation without requiring prior cleavage of the receptor by thrombin. The pentapeptide amide Ser-Phe-Leu-Leu-Arg-NH2, which retains the N-terminal sequence of the 'tethered ligand' of the receptor, has been shown to be the minimum sequence to cause receptor activation. To understand the importance of the side chains of various residues within the pentapeptide amide, we carried out an extensive structure-activity study of the ability of peptides to stimulate gel filtered platelet aggregation. In this study 106 pentapeptide amides were synthesized, utilizing naturally occurring L-amino acids, unnatural amino acids, D-amino acids and N-methyl amino acids for replacements. At position-1, charged residues (acidic or basic) were not tolerated, and the size and shape of the residue were important. Position-2 tolerated only aromatic residues. Position-3 accommodated various residues. A significant finding of this study was that two very different residues, [3-(2-naphthyl)]-L-alanine and L-arginine, when substituted for leucine residue at position-3, resulted in more active agonists. At position-4 aromatic and aliphatic residues were well tolerated, whereas basic and acidic residues were less tolerated. Position-5 mimicked position-3 in its ability to tolerate a wide range of residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782163 TI - Peptide synthesis using novel S-sulfocysteine derivatives. AB - New cysteine S-sulfonate derivatives, Boc-Cys(SO3Na)-ONa 2 and Fmoc-Cys(SO3Na) ONa 3, were prepared and their utility for peptide synthesis examined. The Fmoc derivative 3 was used in the solid-phase peptide synthesis of Arg8-vasopressin 9 via the Bunte salt 7. Satisfactory S-sulfonate stability was observed when p cresol scavenged the cleavage from the resin. The intermediate 7 was purified by ion-exchange chromatography prior to S-sulfonate cleavage with tributylphosphine. PMID- 7782164 TI - Role of peptide hydrophilicity on determination of microsequencing efficiency. AB - The successful sequencing of short peptides on hydrophobic polyvinylidene difluoride membrane (PVDF-P) has been problematic. In this study the sequencing efficiency of various short synthetic peptides on charged-modified PVDF (PVDF-N) and chemically treated glass-fiber membranes or discs has been examined. These modified membranes provided better repetitive yields or sequencing efficiency than the unmodified PVDF-P. In contrast, there were no significant differences among the resulting initial yields for all the tested membranes, indicating that the modified membranes did not interfere with the coupling/cleaving reactions. Methanol at 1% increased the solubility of phenylisothiocyanate (PITC) in heptane for gas-phase delivery during the coupling reaction, whereas this addition of methanol failed to increase the coupling efficiency. Reduction of chemical background noise by replacing triethylamine (TEA) with diisopropylethylamine (DIPEA) also failed to increase the coupling efficiency. Polybrene strengthened the peptide binding to both PVDF-P and PVDF-N, but increased the amount of carry over of PTH-amino acid from the current cycle to the next. Nonetheless, hydrophilic peptides had higher sequencing recoveries and repetitive yields than hydrophobic peptides when sequenced on all the tested membranes. This relationship was further verified by testing a synthetic peptide with decreasing hydrophilicity by sequential deletions of 2 amino acid residues from its N terminus. A decreasing sequencing efficiency was observed, which correlated with the reduced hydrophilicity and peptide length. Similar results were obtained when testing peptide fragments with decreasing hydrophilicity by deletions of amino acids from the C-terminus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782166 TI - Variability analysis of the T-cell receptors using three variability indexes. AB - In the absence of a three-dimensional structure for TCR molecules, several attempts to identify their hypervariable regions by variability methods have been made; this subjects is still troublesome. In this paper three different variability indexes were used: (i) the Kabat index, which is the classical measure of sequence variability, (ii) the modified Kabat index, successfully used in the beta-chain of T-cell receptors and (iii) an information-theoretical entropy concept, recently proposed as an improved measure of the variability. In order to identify the hypervariable regions in the TCR sequences, a Fourier filtering was applied on each variability profile. Results show that the three variability indexes have distinct resolutions for different levels of variability. Thus, the simultaneous use of these indexes compensates for the deficiency of any one of them in estimating variability. Applying the Fourier filtering, it is found that the hypervariable regions here identified, roughly coincide with the defined CDR-2 and CDR-3 in TCR by analogy with Ig. However, no hypervariable in the CDR-1 of alpha- and beta-chains was found. The study on the influence of sample size in variability analysis, indicates that results are independent of the sample size. Considering current structural models of TCR peptide-MHC interaction, one can suggest that the low-variability characteristics of these regions is inherently related to the interaction with relatively conserved region on the alpha-helices of MHC. PMID- 7782165 TI - Use of the 3-nitro-2-pyridine sulfenyl protecting group to introduce N epsilon branching at lysine during solid-phase peptide synthesis. I. Application to the synthesis of a peptide template containing two addressable sites. AB - TASPs (template-assembled synthetic peptides) are generated by the covalent attachment of linear peptides to a common peptide backbone, thus generating larger synthetic peptides/proteins with prefolded structure. In this work we present a strategy for the synthesis of a heterotemplate-assembled synthetic peptide containing two addressable sites. This orthogonal protection strategy would allow the selective introduction of different peptide chains via the epsilon-amino functions of template lysines being protected by either fluorenylmethoxycarbonyl (Fmoc) or 3-nitro-2-pyridine sulfenyl (Npys) groups. The N alpha-Boc-N epsilon-Npys-L-lysine required for solid-phase peptide synthesis (SPPS) is not readily available at a reasonable cost. To facilitate the more widespread use of this reagent we have compared the two published procedures for synthesizing this protected amino acid and evaluated the suitability of the products for SPPS. Two resin-bound peptides, a tripeptide Ac-G-K-Npys)-G-resin and an octapeptide template Ac-P1-K2-K3-L4-K5-K6-P7-G8-resin, were synthesized by SPPS. The epsilon-amino functions of lysines K2 & K6 and K3 & K5 of the octapeptide were protected by Fmoc and Npys groups, respectively. Secondly, these peptides were used to evaluate various reagents and reaction conditions for the deprotection of the epsilon-amino function of lysines bearing the N epsilon-Npys protecting group. A procedure for the optimized selective and quantitative deprotection of the Npys group from the epsilon-amino function of lysine in a resin-bound peptide using 2-mercaptopyridine-N-oxide is described. PMID- 7782167 TI - Single diastereomeric desaminotyrosylalanyl tetra- and heptapeptides with opioid antagonistic activity. AB - The N-terminal dipeptide Tyr-d-Ala of a mu-selective agonist, dermorphin tetrapeptide (DT, H-Tyr-D-Ala-Phe-Gly-NH2) and delta-selective agonist deltorphin C (DEL-C, H-Tyr-D-Ala-Phe-Asp-Val-Val- Gly-NH2) was changed into an aminodiacyl moiety. The relevant synthetic step is a nucleophilic substitution of bromine from a chiral 2-bromopropanamide by the amino group of tyrosine, with overall retention of configuration. The resulting pseudo tetra- and heptapeptides I-VI were characterized for mu- and delta-opioid receptor binding properties using [3H]DAGO and [3H]DPDPE, respectively, and in a bioassay using guinea pig ileum (GPI) and mouse vas deferens (MVD). As a result of chemical alteration of N terminal depeptide moiety, all synthesized analogs showed considerable reduction in opioid receptor affinity compared to mu- and delta-prototypes (500-fold on the mu-site, analog I, and 125-fold on the delta-site, analog IV). Interestingly, analogs I and IV showed moderate antagonist activity, respectively, on GPI and MVD, with pA2 values of 6.05 and 6.82. Analog IV did not exhibit the delta antagonist potency and delta-selectivity of TIPP peptides. PMID- 7782168 TI - Ras-dependent maturation of Xenopus oocytes is blocked by modified peptides of GTPase activating protein (GAP). AB - Guanosine triphosphatase activating protein (GAP) is an important modulator of p21ras (Ras)-dependent signal transduction in mammalian cells and in insulin induced maturation of Xenopus oocytes. A synthetic octapeptide from the catalytic domain of GAP, residues 899-906 (F899VFLRLIC906), inhibited GAP-stimulated hydrolysis of GTP to GDP by Ras in an in vitro biochemical assay (IC50 = 12 microM). The peptide was assayed for its ability to block insulin- (Ras dependent) and progesterone- (Ras-independent) induced maturation of stage VI Xenopus laevis oocytes, marked by germinal vesicle breakdown (GVBD). Microinjection of 50 pmol of the peptide inhibited insulin- but not progesterone induced GVBD by 50%. A 7-residue peptide lacking F899, GAP(900-906)-NH2, failed to inhibit GAP-stimulated GTPase activity and did not block GVBD. Replacement of the cysteine residue at position 906 with methionine resulted in a peptide with prolonged inhibitory activity in the oocyte. Moreover, sequential replacement of specific L-amino acid residues with the corresponding D-amino acids produced a peptide with a two-fold increased half-life after injection into oocytes. None of the peptides tested affected progesterone induced GVBD, suggesting that the modifications did not result in loss of specificity. These studies show that (a) peptides that were able to inhibit GAP-stimulated Ras GTPase activity in vitro were also able to block Ras-dependent GVBD in oocytes, and (b) specific substitutions in these peptides can result in improved stability in oocytes. PMID- 7782169 TI - Probing the structure of human growth hormone by limited proteolysis. AB - Digestion of human growth hormone (hGH) with the Glu-specific protease from Staphylococcus aureus V8 was performed at 20-22 degrees C or 37 degrees C at a 1:20 ratio (by weight) at pH 7.8 with or without 0.2% SDS. There are 14 Glu residues evenly distributed along the polypeptide chain of hGH as possible sites of proteolytic cleavage of V8-protease. The pattern of fragmentation of hGH was analyzed by electrophoresis and reversed-phase HPLC, and the identity of the proteolytic fragments isolated to homogeneity was established by their partial sequencing and amino acid analysis after acid hydrolysis. Kinetic analysis of the proteolytic digestion process allowed to establish that initial nicking of the protein occurs at Glu33 and subsequently at Glu56 and Glu66. Much slower cleavages occur at Glu30 and Glu186. These cleavage sites are located at chain loops in the hGH molecule, and in particular outside the helical segments of the four-helix bundle of the crystal structure of hGH. Fragments 1-33 and 67-191 comprising entirely the N-terminal helix and the three C-terminal helices of hGH, respectively, were isolated to homogeneity in amounts useful for subsequent conformational and functional studies. The results of this study and of previous ones [Li, C.H. (1982) Mol. Cell. Biochem. 46, 31-41] describing limited proteolysis of hGH by various proteases have been interpreted on the basis of the three-dimensional structure and dynamics of hGH. Overall, it is shown that proteolytic enzymes preferentially cleave hGH at exposed and flexible loops only, thus emphasizing the fact that proteases can be used as reliable probes of protein structure and dynamics. PMID- 7782170 TI - Peritonsillar abscess in children. Is incision and drainage an effective management? AB - Debate continues concerning proper management of peritonsillar abscess (PA). We studied 189 children (mean age, 9 years) admitted in our department during the last 7 years with the diagnosis of PA. Management consisted of incision and drainage (performed in 92.5% of the children without general anaesthesia) and antibiotic therapy intravenously. There was resolution without complications in the overwhelming majority of the cases. After the initial episode, we further followed up 101 children. The recurrence rate was 15.8%. Forty-seven percent of the recurrences occurred 1 month after the children had been discharged. Probably some of these second PA should be considered as persistent and not as recurrent. Therefore, we propose that after their discharge, the children must take oral antibiotics (resistant to beta-lactamase) for more than 10 days. Cultures were taken from 58 cases. The predominant bacterial isolates were Streptococcus spp. (55%), anaerobes spp. (12%) and Staphylococcus aureus (6%). To our knowledge, this is the first survey that addresses exclusively a pediatric population and suggests that incision and drainage without general anaesthesia is an applicable and effective management in children with PA. Moreover, we believe that peritonsillar abscess is no longer a strong indication for tonsillectomy due to the relatively low rate of recurrence. We recommend close follow-up, mainly for the first months after the initial episode. PMID- 7782171 TI - Auditory brainstem responses in children with Cornelia de Lange syndrome. AB - Auditory brainstem evoked responses (ABRs) were recorded in 10 Japanese infants and children with Cornelia de Lange syndrome to determine the level of the lesion causing their poor response to sound. Behavioral audiometry showed severe threshold elevation compared to an age-matched control group. ABR thresholds, peak latencies of wave I and IV and the peak interval latency of waves I-V were measured. ABR abnormalities of 4 types: no ABRs following 85 dB clicks in both ears (4 cases), no ABRs in one ear but normal ABR in the other (2 cases), mild wave V threshold elevation of ABR with a markedly prolonged wave V (2 cases) and normal ABR pattern in the one side and abnormal ABR pattern in the opposite side suggesting brainstem immaturity for age (2 cases). Our results demonstrate a high prevalence of peripheral sensorineural hearing loss in Cornelia de Lange syndrome, but brainstem immaturity was not ruled out in 2 cases. PMID- 7782172 TI - Acute mastoiditis in pediatric age. AB - The object of the present paper is to review 39 cases of acute mastoiditis treated surgically at the 2nd and 4th ENT Clinics of the University of Rome 'La Sapienza'. The aetiological factors were investigated observing an association of the acute mastoid abscess with cholesteatoma. Moreover 5 patients developed mastoiditis after previous mastoid surgery. The rationale of surgical management is discussed. PMID- 7782173 TI - Role of anaerobic bacteria in chronic otitis media and cholesteatoma. AB - Otitis media (OM), a common infection in children, can cause significant morbidity. Selection of the most appropriate treatment regimen directed against the pathogens responsible for the OM can minimize complications. The most frequently isolated bacteria from chronic OM are Staphylococcus aureus, Pseudomonas aeruginosa and anaerobic bacteria. The predominant anaerobes are Peptostreptococcus spp., pigmented Prevotella and Porphyromonas spp., Bacteroides spp. and Fusobacterium spp. Many of the organisms causing OM can produce beta lactamase, which can contribute to the failure of penicillins therapy. The appropriate surgical and medical therapy for chronic OM is reviewed. PMID- 7782174 TI - The Usher syndrome type 2A: clinical findings in obligate carriers. AB - Ten obligate carriers of Usher syndrome type 2A from 5 different families with 2 affected persons all underwent audiologic, vestibular and ophthalmologic examinations. They had a sensorineural hearing loss which was in excess of that expected for their age at all of the frequencies (0.25-8 kHz) tested, however, only a 10 dB (average) excess in hearing loss at 0.25-0.5 kHz proved to be significant. The speech discrimination scores obtained conformed with the hearing thresholds. Tympanometry, acoustic reflex and brain stem auditory-evoked potential findings were generally normal. Some vestibular abnormalities were found in a minority of the carrier sample, but not beyond the level of false positivity. Ophthalmologic findings were essentially normal, although in 5 carriers there was a subnormal electrooculography (EOG). These findings are not sufficient specific for carrier detection. PMID- 7782175 TI - Screening for neonatal and infant deafness in Europe in 1992. AB - Many methods of screening for hearing impairment are available. The aim of our study was to determine which ones were really used in 1992. At the request of the British Audiology Society, we conducted an inquiry into the organization of screening for deafness in neonates and infants in Europe. In practice all 6-9 month-old infants are tested with behavioural tests in every country. For the neonates, generally only those at risk for hearing-impairment (about 5%) were tested. The most widely used tests were behavioural ones. Only specialized centers used transient evoked otoacoustic emissions (TEOAEs). This last test assesses the active mechanical properties of the cochlea and allows detection of even mild or unilateral sensorineural deafness. PMID- 7782176 TI - Development of aerodynamic aspects in children's voice. AB - To determine the changes with increasing age in children this study measured the air flow and the acoustic signal in children aged 4-15 years. The subglottal pressure was estimated from the intraoral pressure during the phonation of the word 'ipipi'. From these parameters the glottal resistance and the glottal efficiency were calculated. Since these parameters depend on the sound pressure level, a linear regression of the parameters versus the sound pressure level was done, and the values for 75 dB SPL were taken for statistical analysis. The study found a subglottal pressure in younger children between 6 and 10 cm water column, which seemed to diminish with age. The phonatory flow rate was between 50 and 150 ml/s in younger children, which seemed to increase with age. The glottal resistance did not depend on age, values of 20-250 Ns/m5 at a sound pressure level of 75 dB exceed those for adults given in the literature. The measurements for the glottal efficiency showed a broad variability between 20 ppm and 400 ppm. PMID- 7782177 TI - Word-initial voicing in the productions of stops in normal and preterm Italian infants. AB - It has been traditionally held that developmental anomalies in language acquisition are more frequent in neonatologically at-risk subjects. There is some suggestion that proficiency in phonology is correlated with motor control development. The purpose of this paper was to compare the patterns of acquisition of the control of the acoustic-phonetic cues for voicing in the speech of premature infants and controls. The measure studied was initial stop consonant voice onset time (VOT), which is known to be the most reliable acoustic cue for the distinction between voiced and voiceless stops. The total population of the study consisted of 7 infants born at less than 37 weeks gestation and a control group of 7 infants born full-term at normal weight; 7 adults, aged 24-26 years, also participated. Each child was recorded under standard recording conditions saying words contrasting labial, dental and velar voiced and voiceless initial stops. Elicited word productions were collected monthly from infants, at different age levels, ranging from 18 to 21 months. The results show that the subjects are more advanced in the acquisition of the appropriate VOT values for the voiceless than for the voiced consonants. This difficulty may be related to the increased neuromuscular control and more complex muscle activity necessary for maintaining voicing during the closure, especially for velar stops. It is important to recognize the possibility that increased variability in preterm children may be related to some neuromuscular immaturity. PMID- 7782178 TI - A prospective randomised trial of the use of sodium bicarbonate and hydrogen peroxide ear drops to clear a blocked tympanostomy tube. AB - This randomised prospective trial compared the efficacy of sodium bicarbonate and hydrogen peroxide ear drops in clearing a blocked tympanostomy tube. Tympanostomy tubes, 110 in number, obstructed with blood or inspissated secretions were randomised into treatment and control groups. Details of the operative procedure were retrospectively collected from the patients notes. The patients were reviewed after 2 weeks for both clinical and tympanometric evidence of clearance of the tube and evidence of complications of the drops. There was no significant therapeutic advantage between the two drops (P > 0.9), but in both treatment arms there was a significant therapeutic advantage over a period of observation (P < 0.05 in both groups). Otorrhoea and pain on instilling the drops occurred with equal incidence in both treatment groups. As obstruction of tympanostomy tubes is a common occurrence which often prompts surgical reventilation, there is great potential for cost savings if conservative treatment can be used effectively. The treatments for obstructed tympanostomy tubes are reviewed and methods of prevention of this common occurrence are discussed. PMID- 7782179 TI - The effect of post-operative diet on recovery in the first twelve hours after tonsillectomy and adenoidectomy. AB - The effect of post-operative diet selection on the recovery rate of 100 children ages 3-17 years undergoing tonsillectomy and adenoidectomy (T & A) was studied. In the first 12 h after T & A children were allowed either a 'restricted' diet of only soft foods and liquids or a 'non-restricted' diet of foods preselected and usually eaten by the child. Parental evaluation of the child's general well being, pain level and nausea were evaluated. The number of episodes of emesis, doses of acetominophen and the list of foods and drinks consumed were also recorded. No significant differences in any aspect of recovery were noted between groups. However, a trend towards decreased nausea and parental perception of a more successful general recovery was noted at 12 h in the 'non-restricted' group. Children in the 'non-restricted' group were able to eat foods more often associated with their regular diet. No child from either group experienced any immediate or delayed complications. Implications for children and their families undergoing T & A are discussed. PMID- 7782180 TI - Children who could benefit from a cochlear implant: a European estimate of projected numbers, cost and relevant characteristics. AB - The incidence of profound hearing impairment by the age of 5, derived from a number of retrospective studies in the UK (population about 58 million; birth rate 14/1000), is estimated to be about 300 per annual birth cohort in the 1990s. This estimate includes 80 children who might be expected to acquire deafness in those first 5 years. Projected to Europe as a whole (population 511 million; birth rate 12/1000) this would mean a population who should be considered as potential cochlear implant patients of some 2268 children, given a variety of assumptions. At a take-up rate of 25% for both congenital and acquired cases of profound hearing impairment this would imply a European-wide expenditure of the order of 17 pounds m/p.a. on hardware and associated rehabilitation programmes. The need for such programmes is explored, in the context of strategies of early identification of hearing impairments. PMID- 7782181 TI - Airway obstruction in the Crouzon syndrome: case report and review of the literature. AB - Craniofacial dysostosis (Crouzon syndrome) is a syndrome characterized by premature closing of calvarial and cranial base sutures as well as those of the orbit and maxillary complex. Orofacial manifestations of this disease include maxillary hypoplasia, external nasal deformity, and prognathism. Airway distress is a well described feature of this syndrome, and both upper and lower airway obstruction may be present in the Crouzon syndrome. Obstructions in the upper airway have been reported secondary to septal deviation, midnasal and choanal abnormalities, and nasopharyngeal narrowing. This study presents a child with the Crouzon syndrome who required tracheotomy during the first 2 years of life for airway obstruction caused in the newborn period (first 6 months) by midnasal stenosis and laser (6 months to 2 years) compounded by soft palate obstruction at the level of the oro/hypopharynx. A review of the English language literature revealed one similar patient presentation but no comprehensive review of this subject. Previously reported airway anomalies are reviewed and airway management is discussed in patients with Crouzon syndrome. PMID- 7782182 TI - Alternatives in the management of aneurysmal bone cysts of the mandible. AB - Aneurysmal bone cyst (ABC) is an unusual expansile lesion of bone which may arise within the mandible on rare occasions. This lesion may arise with very few signs or symptoms. Surgical treatment consists of complete excision or curettage. The recurrence rate may be high in lesions which are incompletely excised. Three cases of aneurysmal bone cysts in children will be presented, demonstrating the wide variation of clinical presentation. One case required an extensive mandibular resection, necessitating the first reported microvascular mandible reconstruction for this entity in a pediatric patient. PMID- 7782184 TI - Congenital nasal pyriform aperture stenosis as a presenting feature of holoprosencephaly. AB - Congenital nasal pyriform apertures stenosis (CNPAS), a recently recognized uncommon cause of nasal airway obstruction, can be a life-threatening circumstance in the neonate. This study's experience with six cases confirmed the suggestion that CNPAS represents a manifestation of holoprosencephaly. Management of this condition depends firstly on the overall prognosis of the patient and secondly the severity of obstruction. Patients with poor overall prognosis should be managed conservatively with an oropharyngeal airway. In patients with a good outlook, the choice of treatment is conservative for those with less severe obstruction and surgical correction for those with complete obstruction. The ability to pass a No. 5Fr catheter (O.D. 1.67 mm) may be a guide to the choice of treatment. An increase in awareness among otolaryngologists on the nature of CNPAS is necessary to improve overall management of such patients. PMID- 7782183 TI - Recurrent respiratory papillomatosis in the larynx: re-emergence of clinical disease following surgery. AB - The treatment and aetiology of recurrent respiratory papillomatosis remains unclear. We report a case of laryngeal papillomatosis where repeated suction diathermy and later laser treatment led to the formation of a substantial glottic web, but a clinically papilloma-free state of the upper aerodigestive system. Division of the web led to widespread recurrence of the papillomas, which eventually resolved after the larynx had healed with the reformation of a limited anterior web. The role of surgical trauma and its effect on re-emergence of papillomas is discussed. PMID- 7782186 TI - Outcomes of ultrasound diagnosis of ectopic pregnancy. Dependence on observer experience. AB - BACKGROUND: The effect of examiner experience on the detection of ultrasound findings in ectopic pregnancy was assessed in a retrospective study. METHODS: Records and examinations of 267 consecutive patients with surgically proven ectopic pregnancy were reviewed. Patients were divided into two groups: (1) those who were examined by faculty during the day (182 examinations) and (2) those who were examined by resident physicians at night (85 examinations). RESULTS: A statistical difference was found in the incidence of adnexal mass, free fluid, sac within the mass, and corpus luteum cyst. CONCLUSION: Examiner experience has a strong effect on the diagnostic accuracy of ultrasound examination. Adnexal abnormalities may be difficult to identify because of confusion with loops of bowel or other pelvic structures. Faculty follow-up and review are important in patient management. PMID- 7782185 TI - Transcatheter occlusion of patent ductus arteriosus using a newly developed self expanding device. Evaluation in a canine model. AB - RATIONALE AND OBJECTIVES: A new occlusion device designed for use in a patent ductus arteriosus was tested in an animal model. METHODS: The device consists of a self-expanding conical-shaped stainless steel mesh, with hooks encircling the expanding end acting to secure the device within the ductus. A screw thread at the apex allows attachment to a stylet, and a 6 F delivery system is used. Placement of the device was attempted in 20 canines that previously had a vascular graft surgically inserted between the descending thoracic aorta and main pulmonary artery, creating the patent ductus model. Angiographic follow-up at regular intervals was performed over a 3-month period. RESULTS: Early cases resulted in device misplacement and migration because of inaccurate assessment of ductus position and size. In 15 canines the device was placed within the ductus and regularly assessed over the 3-month placement period. Ductus occlusion occurred within 1 week in 12 of 13 dogs (92%) when device placement was considered ideal. In two dogs where significant protrusion of the device from the ductus was evident (either into the aorta or main pulmonary artery) ductus closure was delayed but present by 3 months, resulting in a 93% overall closure rate at this time. In one dog, the ductus remained partially opened. CONCLUSIONS: This self-expanding patent ductus arteriosus occlusion device is promising. The 6 F delivery system is advantageous over other devices currently available, making it more suited for use in the pediatric population. Accurate assessment of the ductus is imperative, however, to enable correct device sizing. The screw thread system allows the device to be repositioned if desired prior to deployment. PMID- 7782187 TI - Magnetization transfer magnetic resonance imaging of parenchymal lung disease. AB - RATIONALE AND OBJECTIVES: Magnetic resonance imaging with magnetization transfer (MT) contrast recently has been described as a method that may provide additional information about the macromolecular composition of tissue. Magnetization transfer contrast images were compared to conventional gradient-recalled echo images in a variety of pulmonary parenchymal diseases and normal lung. METHODS: Single-slice gradient echo images were obtained with and without an off-resonance radio frequency pulse on a 0.1T MR scanner. The change in signal intensity between identical regions of interest on non-MT and MT images was determined in 13 patients with known lung disease, five healthy volunteers, and three postmortem atelectatic dog lungs. RESULTS: No significant change in signal intensity (MT effect) was observed in fat, flowing blood, normal lung, atelectatic lung, or in acute pulmonary edema. Chronic parenchymal lung disease showed the greatest MT effect, 37.7% +/- 7.5. Acute infectious lung disease showed an intermediate degree of MT effect, 19.5% +/- 3.0. CONCLUSIONS: Magnetization transfer contrast magnetic resonance imaging of pulmonary disease is feasible at low field strength and may be useful in the characterization and differentiation of pulmonary parenchymal abnormalities. Magnetization transfer contrast appears to be proportional to the amount of interstitial fibrosis in lung parenchyma, while acute inflammatory cell infiltration exhibits less MT effect and acute pulmonary edema exhibits very little. PMID- 7782188 TI - Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP DO3A, an extracellular agent, in healthy liver and metastatic disease. AB - RATIONALE AND OBJECTIVES: A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy2DOTA, was compared in two animal species with Gd HP DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. METHODS: The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. RESULTS: Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted in both monkeys and rabbits after injection of Gd Cy2DOTA. Two minutes after contrast, liver SI was 1.94 +/- 0.05 with Gd Cy2DOTA compared with 1.51 +/- 0.05 with Gd HP DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 +/- 0.09 compared with 1.20 +/- 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy2DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy2DOTA and 5 minutes after injection of Gd HP-DO3A. Sixty minutes after injection, liver-lesion contrast was 246 +/- 61 with Gd Cy2DOTA and 106 +/- 28 with Gd HP-DO3A, with a significant difference (P < 0.02). CONCLUSIONS: Gd Cy2DOTA provides greater enhancement of the liver parenchyma on immediate and delayed magnetic resonance scans than does Gd HP-DO3A. On delayed scans, Gd Cy2DOTA provides superior delineation of metastatic liver lesions. PMID- 7782189 TI - Changes in the microcirculation of the intact rat heart after iodinated and gadolinium-containing contrast media. AB - RATIONALE AND OBJECTIVES: A new model was developed to study microcirculation in the intact heart of the anesthetized rat, and the effects of roentgenography and magnetic resonance imaging contrast media were investigated. METHODS: Roentgenography contrast media (600 mg iodine/kg), gadopentetate (0.25 mmol/kg), or physiological saline were injected intraarterially into anesthetized rats (N = 10) whose chests had been opened in a pressurized container. The effects on arterial and venous vasomotion and microhemodynamics of the capillary network were determined in vivo by combined incidental light-fluoroscopic microscopy using continuous 35-mm cine film and video recordings from 5 minutes before until 20 minutes after injection. The amplitude and frequency spectra were evaluated according to the Prony method and by Fourier analysis. Additionally, the number of perfused vessel bifurcations were counted. RESULTS: Gadopentetate exhibited no effects on microcirculation, and diatrizoate exhibited the largest ones. The deformation of the vasomotion spectrum reached 28%, and bifurcations were reduced by 21%. The effects were reversible within 10 minutes of injection. Iotrolan showed minimal disturbance. The other contrast media (iopromide, iopamidol, ioxaglate) fell between these two extremes. CONCLUSION: High-osmolar ionic roentgenography contrast media resulted in a transient deregulation of vasomotion and in a disturbed microcirculation in the rat heart. Isotonic or low-osmolar nonionic roentgenography contrast media or gadopentetate did not show this effect or showed it only to a minimal extent. PMID- 7782190 TI - Safety and efficacy of dotarem (Gd-DOTA) versus magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. AB - RATIONALE AND OBJECTIVES: Gd-DTPA is a well-characterized, safe contrast agent frequently used in magnetic resonance imaging (MRI) of the central nervous system. The purpose of this double-blind, comparative MRI study of brain, spine, trunk, and limbs was to evaluate the safety and efficacy of Gd-DOTA versus Gd DTPA in a large number of patients (n = 1038). METHODS: T1-weighted MRI was performed before contrast and after the administration of Gd-DOTA or Gd-DTPA (0.1 mmol/kg). The MR images were scored for image quality, and the diagnostic efficacy also was assessed. Patients were questioned 1 hour after injection, and adverse reactions were recorded. RESULTS: Image quality of the T1-weighted MR images without contrast was good or excellent in 89.7% and 91.7% of the Gd-DOTA and Gd-DTPA groups, respectively (P > 0.2). After contrast, 85.8% (Gd-DOTA) and 88.2% (Gd-DTPA) of the T1-weighted MR images were of good to excellent image quality (P > 0.2), significantly less than before contrast (P < 0.001, both groups). In 82.3% of the Gd-DOTA group and 83.5% of the Gd-DTPA group (P > 0.2), the information obtained was more accurate with the administration of contrast agents. In 82.4% (Gd-DTPA) and 81.9% (Gd-DOTA) of patients, confirmation was obtained of diagnosis without contrast, whereas in 17.0% and 17.3% of patients, therapy was modified as a result of the use of contrast (P > 0.2, both groups). The MRI investigation was reported as abnormal in 58.3% (Gd-DOTA) and 59.6% of patients (Gd-DTPA), indicating a similar prevalence of disease in each group. Patients responded that 97.8% (Gd-DOTA) and 98.5% (Gd-DTPA) of the investigations went well and adverse reactions, none of them serious, were encountered in 0.97% of Gd-DOTA and 0.77% of Gd-DTPA groups (P > 0.2, both groups). CONCLUSION: This double-blind, randomized, clinical trial comparing Gd-DTPA and Gd-DOTA revealed no serious adverse reactions, whereas minor adverse reactions were encountered in fewer than 1% of patients. Gd-DOTA is as safe a contrast agent as Gd-DTPA and has similar diagnostic efficacy. PMID- 7782191 TI - Radiation-induced lung injury using a pig model. Evaluation by high-resolution computed tomography. AB - RATIONALE AND OBJECTIVES: To assess the early phase of radiation-induced lung injury using high-resolution computed tomography (CT) under experimental conditions and to perform precise CT-pathologic correlation. METHODS: Five Yorkshire pigs received a single dose of 12.5 Gy to the right lower lung. Computed tomographic images were obtained at 2-week intervals. The animals were killed after follow-up periods of 4-16 weeks. The lungs were removed, inflated, fixed, dried, and sliced corresponding to the CT sections. Computed tomography, specimen radiography, and histologic findings were correlated. RESULTS: Various CT findings were observed during the first 16 weeks, including ground-glass opacity, discrete consolidation, patchy consolidation, thickened interlobular septum, and bronchovascular bundle. Ground-glass opacity was associated with thickened alveolar wall and scattered tiny fibrotic foci. Thickened interlobular septum and bronchovascular bundle were the results of fibrosis adjacent to these structures. Discrete consolidation correlated with intraalveolar edema with hemorrhage and infiltration of inflammatory cells. CONCLUSIONS: High-resolution CT correlated well with pathology of the lung due to radiation injury as verified by precise radiologic-pathologic correlation. PMID- 7782192 TI - Validation of right ventricular volume measurements by magnetic resonance imaging in small hearts using a fetal lamb model. AB - RATIONALE AND OBJECTIVES: Cine-magnetic resonance (MR) imaging is established as an accurate method of determining cardiac ventricular volumes in adults but has not been validated for the smaller ventricular volumes found in infants. The purpose of the authors study was to evaluate the accuracy and reproducibility of MR imaging to measure small ventricle volumes. METHODS: The volume of silicone rubber casts of the right ventricle of 11 fetal lamb hearts was measured by MR imaging using different imaging planes and slice section thicknesses and by water displacement. RESULTS: The ventricle volumes of the 11 hearts ranged from 0.45 to 3.00 mL. Accurate and reproducible values for the right ventricle volumes were obtained by MR imaging. Thin sections (3 mm) in the axial plane produced the best results. CONCLUSIONS: Based on studies in the nonmoving heart, MR imaging can accurately measure the small ventricular volumes expected in infants. PMID- 7782193 TI - Flow cytometric evaluation of platelet activation by ionic or nonionic contrast media and modulation by heparin and recombinant hirudin. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the platelet activation properties of ionic and nonionic contrast media in native heparinized or hirudinized human blood using flow cytometric analysis techniques. MATERIALS AND METHODS: Freshly drawn human blood samples were incubated at 37 degrees C with ionic (Hexabrix and Angiovist) and non-ionic (Isovue and Omnipaque) contrast media for varying periods of time. Using fluorescent monoclonal antibodies to platelet surface receptors glycoprotein IIIa and with granule membrane protein-140, platelet activation was measured in whole blood using flow cytometry. Platelet factor 4 and thromboxane B2 levels also were measured. RESULTS: Dose- and time-dependent platelet activation was observed in nonionic, but not in ionic, contrast media (P < 0.05). Whole blood drawn into heparin or hirudin showed reduced platelet activation in the presence of contrast media compared with nonanticoagulated whole blood. Platelet factor 4 and thromboxane B2 levels showed similar results. Significant platelet activation was seen by flow cytometry in high (2000 mOsmol/kg), but not in lower osmolality (800 mOsmol/kg) controls for ionic and nonionic contrast media, respectively (P < 0.001). CONCLUSION: This study suggests that nonionic contrast media use is associated with significant levels of platelet activation, and that heparin or recombinant hirudin (where heparin is contraindicated) is preferable for use with nonionic contrast media, as these anticoagulants reduce contrast media induced platelet activation. PMID- 7782194 TI - Great moments. Parke, Davis and Company and the creation of medical art. PMID- 7782195 TI - The hospital-based attorney as patient advocate. PMID- 7782196 TI - Wrong necessity. PMID- 7782197 TI - Baby Ryan and virtual futility. PMID- 7782198 TI - Bethann's death. PMID- 7782199 TI - Two theories of modernity. PMID- 7782200 TI - Abandoning informed consent. PMID- 7782201 TI - Benign parotid adenomas: a review of the Princess Margaret Hospital experience. AB - BACKGROUND: The morbidity of treating benign parotid tumors is an important issue because the majority of patients are young. We therefore undertook this study to evaluate the outcome for these patients treated at the Princess Margaret Hospital. METHODS: A retrospective review was conducted on all patients registered with benign parotid tumors between 1970 and 1987. RESULTS: Seventy-six patients were included in this review; postoperative radiotherapy (XRT) was administered to 55 patients. Median follow-up time was 12.5 years. Postoperative XRT was particularly important for patients with recurrent disease. The risk of both temporary and permanent facial nerve paralyses increased with each operation. No patients in this study developed a malignancy. CONCLUSIONS: We recommend that all patients with benign parotid tumors be treated with a complete parotidectomy with preservation of the facial nerve. Consideration to postoperative XRT should be given to patients in whom there was tumor spillage, residual disease, or recurrences. PMID- 7782202 TI - Mucosal melanoma of the nasal cavity and paranasal sinuses. AB - BACKGROUND: Mucosal melanomas of the nasal cavity and paranasal sinuses are rare and do poorly. METHODS: Seventeen patients treated from 1981 to 1993 at a single referral center were retrospectively reviewed. RESULTS: Thirteen patients underwent surgical resection, with seven receiving postoperative radiotherapy. Eight had microscopically negative margins. The actuarial 2-year and 5-year survivals for this group of 13 were 67% (8 of 12) and 20% (2 of 10). The local recurrence rate was 85% (11 of 13) and distant metastases occurred in 31% (4 of 13) patients. In the absence of metastatic disease, resection of recurrent tumor correlated with disease-free intervals ranging from 3 months to 40 months. CONCLUSIONS: Those who received postoperative radiotherapy appeared to have done better with increased disease-free intervals and prolonged survival. Negative surgical margins were not predictive of a more favorable outcome. Surgical resection followed by postoperative radiotherapy is appropriate and resection of recurrent tumor should be considered. PMID- 7782203 TI - Retropharyngeal adenopathy as a predictor of outcome in squamous cell carcinoma of the head and neck. AB - BACKGROUND: Little information about the incidence of retropharyngeal adenopathy and its impact on prognosis has been published. METHODS: For 774 patients with squamous cell carcinoma of the nasopharynx, oropharynx, hypopharynx, or supraglottic larynx, pretreatment CT and, in selected cases, MRI scans were reviewed to determine the presence of retropharyngeal adenopathy. Results were analyzed in 619 patients treated with curative intent to determine the prognostic impact of retropharyngeal adenopathy. RESULTS: The highest incidence of retropharyngeal adenopathy was seen in patients with nasopharyngeal (74%) and pharyngeal wall (19%) cancers. The number of cervical nodal groups involved was the most significant factor (p < .0001) relating to the incidence of retropharyngeal adenopathy. The rates of neck relapse (40% at 5 years) and distant metastasis were significantly higher in patients with retropharyngeal adenopathy, and the rates of 5-year relapse-free survival and absolute survival were significantly lower. CONCLUSIONS: Retropharyngeal adenopathy is a strong predictor of poor prognosis, particularly for patients with advanced neck disease. PMID- 7782204 TI - Extent of lymph node dissection in T3/T4 cancer of the alveolo-buccal complex. AB - BACKGROUND: Cancer of the alveolo-buccal complex even when locally advanced is amenable to curative resection. However, the extent of lymph node dissection remains controversial. METHODS: A total of 181 patients with T3/T4 cancer of the alveolo-buccal complex who underwent a radical neck dissection (RND) were analyzed retrospectively to determine the incidence and pattern of lymph node involvement and to define the extent of neck dissection required in these cancers. RESULTS: Lymph node involvement was as follows: level I (85%), II (51%), III (19%), IV (18%), V (5%). Levels I and II were most commonly involved (94%). Skip metastases occurred in 13%. Levels IV and V were involved in 2% and 20% when levels I, II, and III were uninvolved and involved, respectively. CONCLUSION: A supraomohyoid neck dissection (SOHD) should be performed and subjected to a frozen section evaluation in every patient. If lymph nodes are negative, then SOHD is adequate. If levels I, II, or III are positive, then a RND should be performed. PMID- 7782206 TI - Combined V figure-shaped scapular osteocutaneous and latissimus dorsi myocutaneous flap for composite mandibular reconstruction. AB - BACKGROUND: As early as 1981, the scapular crest was reported as a versatile donor site of vascularized bone flap. In our institute, much attention has been paid to applying a compound flap based on the subscapular vascular system for composite mandibular reconstruction. METHODS: The combined V figure-shaped scapular osteocutaneous and latissimus dorsi myocutaneous flap has been used for primary or secondary reconstruction of the mandible, intraoral mucosa and/or external skin following major ablation of the malignant tumors in seven patients. RESULTS: There was one total flap failure. Satisfactory results were obtained in the remaining patients. CONCLUSIONS: The V figure-shaped scapular bone flap supplied by the angular branch provides a long rotation arc of vascular pedicle, a long bony segment of more than 14 cm, and a good contour of mental protuberance. The combination of the scapular osteocutaneous flap with latissimus dorsi myocutaneous flap allows reliable reconstruction of massive and three dimensional composite mandibular defects. PMID- 7782205 TI - Mesenteric flap in free jejunal transfers: a versatile technique for head and neck reconstruction. AB - BACKGROUND: The technique of free jejunal transfers has been widely used for pharyngoesophageal reconstruction. However, secondary infectious and fistulous complications may develop in extensive and preoperatively high-dose irradiated cases. METHODS: A generous jejunomesenteric composite graft was harvested and the mesenterium was effectively applied for head and neck reconstruction. RESULTS: The mesenteric flap connected with the revascularized jejunum was used as means for obliterating dead space in the head and neck region, as a cover for the cover for the cervical vessels, as a vascularized bolstering for the vascular and enteral anastomoses, or as a vascularized bed for skin grafting when the skin flaps are deficient. Only one small fistula occurred in 10 patients who underwent the mesenteric flap. CONCLUSIONS: This versatile technique is expected to reduce the incidence of postoperative complications in pharyngoesophageal reconstruction using free jejunal transfers. PMID- 7782207 TI - Langerhans' cell histiocytosis: head and neck manifestations in children. AB - BACKGROUND: Langerhans' cell histiocytosis (LCH) is an uncommon, poorly understood granulomatous disease, characterized by the idiopathic proliferation of Langerhan's cells or their marrow precursors. In 1985, the Philadelphia Work shop adopted the term "Langerhans' cell histiocytosis" (LCH) to differentiate it from reactive and neoplastic causes of histiocytosis. METHODS: This study includes 73 pediatric patients diagnosed with this condition in Dublin, Ireland, and Nottingham, England, during a 34-year period (1959 to 1993). These patients are reviewed with respect to clinical presentation, difficulty with making a histological diagnosis, their management, and outcome. RESULTS: A total of 49 patients (67%) had head and neck involvement. Bony involvement was the most frequent sign, most frequently located in the skull. There were 11 deaths (15%) in this series, all associated with multisystem disease, and nine of these deaths were in children younger than 2 years of age. CONCLUSIONS: The role of otolaryngologists is important in the early and accurate evaluation, staging, and diagnosis of LCH. It may mimic more common diseases, such as otitis externa, acute mastoiditis, skin rash, gingivitis, or cervical lymphadenopathy. Patients with multisystem disease may be so ill at presentation that the head and neck lesions may be overlooked. The current management of LCH has become increasingly conservative, and in the 1990s, fewer cases are given chemotherapy or radiotherapy. The prognosis is very good for single-system disease and poor for multisystem disseminated disease with early onset. PMID- 7782208 TI - Radical, modified, and selective neck dissection for cutaneous malignant melanoma. AB - BACKGROUND: The roles of modified and selective neck dissections in treating patients with clinical metastatic melanoma and the place of adjuvant radiotherapy are unclear. In the elective setting, the efficacy of various selective dissections also requires clarification. METHODS: The prospectively documented experience of the senior author (COB) was analyzed. A total of 175 patients had 183 neck dissections and 92 parotidectomies in 6 years. There were 75 therapeutic and 108 elective operations. Modified or selective neck dissections were performed in 58% of patients with clinical neck metastases. Ali but two elective operations were modified or selective dissections. Postoperative radiotherapy was given to 27 dissected necks. Minimum follow-up was 12 months, and 86% of patients were followed up for 2 years or to neck recurrence. RESULTS: Nodes were histologically positive in 80 dissections. The cumulative rate of control of metastatic melanoma in the neck was 86% at 5 years. Neck recurrence developed in 14% of radical dissections, 0% of modified, and 23% of selective dissections performed for clinical disease. Neck recurrence occurred after 5% of elective dissections. Recurrence was 7% among irradiated necks compared to 23% in nonirradiated (p-value not significant). The 5-year survival rate was 50%, and this was significantly worsened by increasing node involvement. CONCLUSIONS: Modified radical neck dissection is highly effective in controlling metastatic melanoma in selected patients. Selective dissections are less effective and need further study. Adjuvant radiotherapy appears to decrease the risk of neck recurrence. In the elective setting, recurrence is uncommon following the selective neck dissections described. PMID- 7782209 TI - The QT interval following carotid artery resection. AB - BACKGROUND: Right radical neck dissection has been shown to prolong the QT interval, reportedly caused by surgical trauma to the cervical autonomic system, which may result in malignant ventricular arrhythmias. Carotid artery resection would be expected to be more likely to cause dangerous arrhythmias. METHODS: We prospectively studied eight patients with electrocardiograms before and after carotid resection. Four patients had left-sided procedures and four patients had right-sided procedures. In addition, 11 patients were studied retrospectively. QT intervals were normal in all patients preoperatively. RESULTS: Preoperative corrected QT intervals (QTc) were in the normal range used by our institution for all eight patients in the prospective group. There were no significant QTc changes after either left-sided or right-sided carotid resection. However, the retrospective group did show significant changes in QTc following right carotid resection (n = 5), but not left resection (n = 6). CONCLUSIONS: EKG changes associated with carotid resection may not be uniform and may depend on surgical technique or specific anatomic factors. Controlled prospective studies are needed to confirm the prevalence of QT interval changes in radical neck surgery. PMID- 7782210 TI - Mandibular resection. PMID- 7782211 TI - Chronic sinusitis in a child. PMID- 7782212 TI - Primary ectopic meningioma of the maxillary sinus: case report and review of the literature. AB - METHODS: A case of a primary ectopic meningioma, arising within the right maxillary sinus, is presented. A review of English literature was also undertaken to determine the prevalence of these lesions in this specific anatomic location. RESULTS: A total maxillectomy was performed without complications and the surgical defect was covered with an immediate obturator. The patient is well and without evidence of disease 3 1/2 years postoperatively. A review of the English literature revealed four additional reports of primary ectopic meningiomas that were limited to the maxillary sinus. CONCLUSIONS: Primary ectopic meningiomas of the maxillary sinus are uncommon lesions which have a good prognosis when a complete resection of the neoplasm can be performed. PMID- 7782213 TI - Epiglottic abscess. AB - BACKGROUND: Epiglottitis is more commonly seen in children less than 6 years of age, although this entity has also been well described among adults. A coalescence of infection of the epiglottis, or epiglottic abscess, has been infrequently reported in series of epiglottitis. Risk factors for epiglottic abscess include adult age at onset, diabetes, and the presence of a foreign body. METHODS: Case study. RESULTS: We present a case of a woman with a 4-day history of febrile illness, odynophagia, and an altered voice. Clinical examination and computed tomography (CT) demonstrated an epiglottic abscess. The patient underwent direct laryngoscopy, intubation, drainage of abscess, and intravenous antibiotics. CONCLUSIONS: The diagnosis of epiglottic abscess should be considered in adult patients initially seen with odynophagia and dysphonia. Principles of treatment include airway management, antibiotics, and surgical drainage. PMID- 7782214 TI - Chemotherapy trials in head and neck cancer. PMID- 7782215 TI - Relationship between physician specialty and the selection and outcome of ischemic stroke patients. AB - OBJECTIVE: This study compares the initial characteristics, in-hospital treatment, and outcomes of stroke patients managed by neurologists versus non neurologists. DATA SOURCES/STUDY SETTING: An inception cohort of 146 patients hospitalized with their first stroke at a private, a university, or a Veterans Affairs hospital. STUDY DESIGN: A prospective, hospital-based, multisite cohort study design is used to ascertain the patients' initial 180-day in-hospital and postdischarge experience. DATA COLLECTION/EXTRACTION METHODS: Data were collected on patient demographics, disease severity, and risk factors for stroke; diagnostic tests and pharmacologic management; one-month and six-month all-cause and cause-specific mortality; and physical and functional impairment. PRINCIPAL FINDINGS: The 88 patients (60 percent) admitted to the neurology services of the study hospitals had better prognostic profiles, i.e., lower likelihood of having either completed stroke or cardiac comorbidity, and were less likely to die within one and six months of stroke onset. CONCLUSIONS: Substantial systematic differences in the types of patients managed by neurologists versus other specialists may preclude comparison of outcomes of care. PMID- 7782216 TI - Commentary: generalist and specialist care of stroke--is there a better way? PMID- 7782217 TI - Commentary: are differences in outcome due to differences in doctors or their patients? PMID- 7782218 TI - Small area variations in health care delivery in Maryland. AB - OBJECTIVE: Our purpose is a descriptive analysis of variations in hospital use among small areas of Maryland. DATA SOURCE: The data are Maryland patient discharge records from acute care hospitals for 1985-1987 and small area population estimates by age, gender, race, and income. FINDINGS: The common finding was excess geographic variability among Maryland's 115 areas. The hypothesis of uniform rates was rejected for most DRGs, including low-variation mastectomy and hernia repair. Clustering of high-use rates occurred in neighboring areas for orthopedic, vascular, and elective procedures. Admission rates for most nondiscretionary procedures and medical DRGs were reduced in affluent areas while discretionary surgery increased with income level. Elective procedures had extreme variation and were related to income. Coronary artery disease rates declined with income while coronary artery procedure rates increased, indicating that access and patient selection were factors in the use of coronary bypass and angioplasty. CONCLUSIONS: The issue is not the ubiquitous variation among small areas but its extent and identification of geographic patterns. Hospital use is related to demography, morbidity, medical resources, access, selection for care, and physician practice patterns. Heterogeneity of these factors ensures that uniform delivery of health care rarely holds. There is little evidence that incidence of surgical disease is the main source of variation in use of discretionary surgery. Rather, variations reflect differing medical opinion on appropriate use. Without evaluation, excessive use cannot be distinguished from underservice. Morbidity explains the variability of nondiscretionary surgery and conditions related to lifestyle. Access plays an important role for discretionary surgery. Geographic analysis can identify variation and relate incidence to socioeconomic and specific local effects. Hospital data do not permit direct assessment of appropriate care. Understanding the reasons for variation requires information beyond incidence data. The challenge is to identify and explain small area variations or to fix them. PMID- 7782219 TI - Mental health care utilization in prepaid and fee-for-service plans among depressed patients in the Medical Outcomes Study. AB - OBJECTIVE: We compare mental health utilization in prepaid and fee-for-service plans and analyze selection biases. DATA SOURCE: Primary data were collected every six months over a two-year interval for a panel of depressed patients participating in the Medical Outcomes Study, an observational study of adults in competing systems of care in three urban areas (Boston, Chicago, and Los Angeles). STUDY DESIGN: Patients visiting a participating clinician at baseline were screened for depression, followed by a telephone interview, which included the depression section of the NIMH Diagnostic Interview Schedule. Patients with current or past lifetime depressive disorder and those with depressed mood and three other lifetime symptoms were eligible for this analysis. We analyze mental health utilization based on periodic patient self-report. ANALYTIC METHODS: We use two-part models because of the presence of both nonuse and skewness of use. Standard errors are corrected nonparametrically for correlations across observations due to clustered sampling within participating physicians and repeated observations on the same individual. PRINCIPAL FINDINGS: The average number of mental health visits was 35-40 percent lower in the prepaid system, adjusted and unadjusted for observed differences in patient characteristics, including health status. Utilization differences were concentrated among patients of psychiatrists, with only minor differences among patients of general medical providers. Analyzing the effect of switches that patients make between payment systems over time, we found some evidence of adverse selection into fee-for service plans based on baseline utilization, but not based on utilization at the end of the study. In particular, after adjusting for observed patient characteristics and health status, patients switching out of prepaid plans had higher baseline use than predicted, whereas patients switching out of fee-for service had lower use than predicted. Switching itself appears to be related to an immediate decline in utilization and was not followed by an increase or "catch up" effect. CONCLUSIONS: The absence of the commonly found "catch-up" effect following switching and the significant decrease in utilization during the switching period suggests an interruption in care that does not occur for patients staying within a payment system. This finding emphasizes the need for integrating new patients quickly into a system, an issue that should not be neglected in the current policy discussion. PMID- 7782220 TI - The impact of prenatal exposure to cocaine on newborn costs and length of stay. AB - OBJECTIVE: Our intention is to determine newborn costs and lengths of stay attributable to prenatal exposure to cocaine and other illicit drugs. DATA SOURCES AND STUDY SETTING: All parturients who delivered at a large municipal hospital in New York City between November 18, 1991 and April 11, 1992. STUDY DESIGN: A cross-sectional analysis used multivariate, loglinear regressions to analyze differences in costs and length of stay between infants exposed and unexposed prenatally to cocaine and other illicit drugs, adjusting for maternal race, age, prenatal care, tobacco, parity, type of delivery, birth weight, prematurity, and newborn infection. DATA COLLECTION/EXTRACTION METHODS: Urine specimens, with linked obstetric sheets and discharge abstracts, provided information on exposure, prenatal behaviors, costs, length of stay, and discharge disposition. PRINCIPAL FINDINGS: Infants exposed to cocaine or some other illicit drug stay approximately seven days longer at a cost of $7,731 more than infants unexposed. Approximately 60 percent of these costs are indirect, the result of adverse birth outcomes and newborn infection. Hospital screening as recorded on discharge abstracts substantially underestimates prevalence at delivery, but overestimates its impact on costs. PMID- 7782221 TI - An integer programming model to limit hospital selection in studies with repeated sampling. AB - OBJECTIVE: We describe an integer programming model that, for studies requiring repeated sampling from hospitals, can aid in selecting a limited set of hospitals from which medical records are reviewed. STUDY SETTING: The model is illustrated in the context of two studies: (1) an analysis of the relationship between variations in hospital admission rates across geographic areas and rates of inappropriate admissions; and (2) a validation of computerized algorithms that screen for complications of hospital care. STUDY DESIGN: Common characteristics of the two studies: (1) hospitals are classified into categories, e.g., high, medium, and low; (2) the classification process is repeated several times, e.g., for different medical conditions; (3) medical records are selected separately for each iteration of the classification; and (4) for budgetary and logistical reasons, reviews must be concentrated in a relatively small subset of hospitals. DATA COLLECTION/EXTRACTION METHODS. In each study, hospitals are ranked based on analysis of hospital discharge abstract data. CONCLUSIONS: The model is useful for identifying a subset of hospitals at which more intensive reviews will be conducted. PMID- 7782223 TI - ISO 9000 series standards: what healthcare facilities need to know. AB - With the recent trend toward implementing or improving quality systems and the increasing frequency with which vendors looking to secure a place in the world market have cited the International Organization for Standardization's (ISO) 9000 Series quality system standards, healthcare facilities have been expressing increased interest in learning about these standards, especially ISO 9001, 9002, and 9003. In this article, we briefly discuss the ISO 9000 Series standards--what they are and what they mean--so that healthcare facilities can properly assess the significance of vendors' statements citing compliance with one or more of these standards. PMID- 7782222 TI - Assessing the impact of continuous quality improvement/total quality management: concept versus implementation. AB - OBJECTIVE: This study examines the relationships among organizational culture, quality improvement processes and selected outcomes for a sample of up to 61 U. S. hospitals. DATA SOURCES AND STUDY SETTING: Primary data were collected from 61 U. S. hospitals (located primarily in the midwest and the west) on measures related to continuous quality improvement/total quality management (CQI/TQM), organizational culture, implementation approaches, and degree of quality improvement implementation based on the Baldrige Award criteria. These data were combined with independently collected data on perceived impact and objective measures of clinical efficiency (i.e., charges and length of stay) for six clinical conditions. STUDY DESIGN: The study involved cross-sectional examination of the named relationships. DATA COLLECTION/EXTRACTION METHODS: Reliable and valid scales for the organizational culture and quality improvement implementation measures were developed based on responses from over 7,000 individuals across the 61 hospitals with an overall completion rate of 72 percent. Independent data on perceived impact were collected from a national survey and independent data on clinical efficiency from a companion study of managed care. PRINCIPAL FINDINGS: A participative, flexible, risk-taking organizational culture was significantly related to quality improvement implementation. Quality improvement implementation, in turn, was positively associated with greater perceived patient outcomes and human resource development. Larger-size hospitals experienced lower clinical efficiency with regard to higher charges and higher length of stay, due in part to having more bureaucratic and hierarchical cultures that serve as a barrier to quality improvement implementation. CONCLUSIONS: What really matters is whether or not a hospital has a culture that supports quality improvement work and an approach that encourages flexible implementation. Larger-size hospitals face more difficult challenges in this regard. PMID- 7782224 TI - Hazard report. Failure of anti-free-flow mechanism in Baxter Flo-Gard 6201/6301 infusion pumps. PMID- 7782225 TI - User experience network. Soldered medical gas piping. PMID- 7782226 TI - Holmium:YAG surgical lasers. AB - "Holmium:YAG (Ho:YAG)" is the shorthand name for a family of solid-state lasers that use the doping element holmium in a laser crystal (e.g., YAG [yttrium aluminum-garnet]) and that emit energy at approximately 2.1 microns. This wavelength is relatively new to medicine and has been used in laser surgery for only about the last six years. Like the carbon dioxide (CO2) laser when it was first used clinically, the Ho:YAG laser is poised for rapid and wide-spread use. Ho:YAG lasers, like CO2 lasers, offer precise cutting with minimal damage to adjacent tissue; however, unlike CO2 lasers, they also offer fiberoptic delivery (which is ideal for endoscopic use) and the ability to treat tissue in a liquid filled environment (e.g., saline, blood). The initial specialty for which the Ho:YAG laser was used was arthroscopic surgery, especially diskectomy. Today, it is effectively used in many surgical specialties, including general surgery, urology, laparoscopy, neurosurgery, lithotripsy, angioplasty, orthopedic surgery (which includes procedures such as meniscectomy, bone sculpting [may also be performed in plastic surgery], and some experimental surgery, such as cartilage shrinking to tighten loose joints), and dentistry. Because of its broad range of potential applications, it has been called the "Swiss Army Knife" of lasers. High powered Ho:YAG lasers, which enable surgeons to work more quickly and cut more smoothly, have been made available only within the last three years (units offering > 20 W) to 18 months (units offering > 60 W). Because of this rapid increase, high-powered units are still relatively expensive, and it is not yet clear whether maximum power outputs will continue to increase or whether the cost of higher-power units will begin to come down. Although low-power and high-power Ho:YAG lasers can be used for the same procedures, their different ranges of possible clinical techniques make them better suited to different applications: low-power units are preferable for small-joint and some head-and-neck surgeries or for office use, and high-power units are more suitable for use in major surgery, such as gastrointestinal surgery or surgery in large joints. This evaluation includes two units at both ends of the Ho:YAG power spectrum--one 10 W and one 60 W--and thus provides a guide to evaluating other Ho:YAG lasers that are currently available or that will be entering the market.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7782227 TI - Inside the beltway 1995. A veterinary view. PMID- 7782228 TI - More on the Andalusian goat rescue. PMID- 7782229 TI - Cross-reactivity between flea and housedust mite antigens? PMID- 7782230 TI - Clients with special needs. PMID- 7782231 TI - Thoughts on retroviruses. PMID- 7782232 TI - Question on classification of terbutaline. PMID- 7782234 TI - AVMA encourages input. PMID- 7782233 TI - Question cause of hypercalcemia in a rabbit. PMID- 7782235 TI - New direction for Center for Veterinary Medicine benefits animals and man. PMID- 7782236 TI - Treatment of perianal fistulas in dogs. PMID- 7782237 TI - Evaluation and dietary considerations in idiopathic hyperlipidemia in dogs. PMID- 7782238 TI - Veterinarians probe greyhound idiosyncrasies. PMID- 7782239 TI - What is your diagnosis? Osteomyelitis, septic arthritis. PMID- 7782240 TI - Urethral obstruction in a pup. PMID- 7782241 TI - Common law and statutory defenses to a veterinary medical malpractice action. PMID- 7782242 TI - Comparison of the efficacies of three heartworm preventives against experimentally induced infections with Ancylostoma caninum and Toxocara canis in pups. AB - Forty 11- to 12-week-old helminth-naive Beagles were categorized by sex and weight and randomly assigned to 4 treatment groups (group 1, ivermectin/pyrantel pamoate; group 2, milbemycin oxime; group 3, untreated control; group 4, diethylcarbamazine/oxibendazole). Each pup was inoculated PO with approximately 100 infective Ancylostoma caninum larvae and 100 larvated Toxocara canis eggs on day 0, and repeatedly at 7-day intervals thereafter until day 56. Administration of anthelmintics also began on day 0, and subsequent treatments were administered according to label recommendations at 30-day intervals (groups 1 and 2) or daily (group 4) for a period of 90 consecutive days. Body weight and A caninum and T canis fecal egg counts were measured at weekly intervals, and clinical observations of health status were conducted twice daily. Pups were euthanatized on day 90, and total gastrointestinal worm burdens were determined. Compared with mean A caninum egg counts of group-3 control pups, egg counts in group-1 pups were significantly (P < or = 0.0001) lower on every sampling days 35, 42, 49, 63, 70, 77, and 84, and were consistently the highest of all treated groups, and egg counts of group-4 pups were significantly (P < or = 0.0001) lower on every sampling date from day 14 to day 90, and were consistently the lowest of all treated groups. Compared with mean A caninum egg counts of group-3 pups, egg counts in group-1 and group-2 pups were lower by 97.8 and 90.8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782243 TI - Intraocular bacterial contamination during cataract surgery in dogs. AB - Prevalence of intraoperative contamination of the eyelids, conjunctival sac, and aqueous humor of 50 canine eyes that underwent elective cataract surgery was determined, and the short-term outcomes for contaminated and noncontaminated eyes were compared by scoring media clarity, pupil size and shape, and behavioral evidence of vision during the initial 30-day postoperative period. Results of bacteriologic culture of anterior chamber samples were positive for 12 of the 50 (24%) eyes, but anterior chamber contamination was unrelated to results of bacteriologic culture of eyelids or conjunctival sac swab samples. Eyes undergoing phacoemulsification were less likely to be contaminated than were eyes undergoing intra- or extracapsular extraction. Eyes undergoing intra- or extracapsular extraction and eyes with anterior chamber contamination had a greater likelihood of developing glaucoma postoperatively. We did not detect an association between intraocular contamination and the surgeon performing the operation, the need for postoperative administration of tissue plasminogen activator, or the presence or absence of diabetes mellitus. Also, we did not detect any differences in outcome between eyes with and without intraocular contamination. Despite intraoperative bacterial contamination of the anterior chamber, bacterial endophthalmitis did not develop in any of the eyes. PMID- 7782244 TI - Seizure classification in dogs from a nonreferral-based population. AB - On initial evaluation for onset of seizure disorders at nonreferral veterinary practices, 50 previously healthy dogs were enrolled in a study to determine the probability of identifying a specific cause for the seizures. Treatment was not administered prior to entry of dogs in the study. On the basis of antemortem and postmortem test results, 22 dogs (44%) were classified as having primary epileptic seizures (PES; idiopathic or without identifiable cause), 23 (46%) had secondary epileptic seizures (SES; identifiable intracranial cause), and 5 (10%) had reactive epileptic seizures (RES; metabolic or transient noxious cause). Forty-one dogs (82%) had 2 or more seizures before evaluation, with 37 (90%) of these dogs classified as having epilepsy on the basis of an underlying chronic brain disorder. For these 41 dogs, 17 (41%) had PES, 20 (49%) had SES, and 4 (10%) had RES. Among the 9 dogs (18%) with nonrecurring seizures, 5 had PES, 3 had SES, and 1 had RES. Generalized seizures were the most common first-observed seizure type associated with all etiologic classifications in all dogs with recurring and nonrecurring seizures. Diagnosis of SES was statistically more probable when the dog was less than 1 or more than 7 years old at the first seizure, when the first seizure was a partial seizure, or when the first seizure occurred between midnight and 8 AM. A diagnosis of RES was statistically more probable only when the interval between the first and second seizure was brief (< or = 4 weeks).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782245 TI - Effect of lente insulin for treatment of diabetes mellitus in 12 cats. AB - Ultralente insulin has replaced protamine zinc insulin as the treatment of choice in treatment of diabetes mellitus in cats. There is variability in effectiveness of ultralente insulin and problems with glycemic control develop in some cats. Alternative insulin preparations are sought when ultralente insulin is ineffective. Twelve cats with insulin-dependent diabetes mellitus were treated with lente insulin. Clinical signs improved in 8 cats given lente insulin every 12 hours. Lente insulin was ineffective in 4 cats. Three of these cats were subsequently found to have an insulin resistant disorder. In 1 cat, lente insulin was ineffective because of short duration of action. Lente insulin is a viable treatment alternative when ultralente insulin is ineffective in achieving glycemic control. Ultralente insulin is still the insulin of choice for the initial treatment of diabetes in cats, because of the potential to establish glycemic control with once-a-day treatment. PMID- 7782246 TI - Noncardiogenic pulmonary edema in dogs and cats: 26 cases (1987-1993) AB - Medical records of 23 dogs and 3 cats treated for noncardiogenic pulmonary edema (NPE) resulting from airway obstruction (n = 8), cranial trauma (7), electric shock (7), or seizures (4) between 1987 and 1993 were reviewed. There were 18 purebred dogs, 5 mixed-breed dogs, 2 domestic shorthair cats, and 1 Siamese. Sixteen animals were male, and 10 were female. All but 7 were less than 1 year old. Time between the inciting incident and onset of respiratory tract signs ranged from minutes to several hours. Respiratory distress was the primary clinical sign for all animals with NPE resulting from airway obstruction, cranial trauma, or seizures, and for 2 of the 7 animals with NPE resulting from electric shock. The only consistent clinicopathologic abnormality was hyperglycemia, which was detected in 12 animals. Arterial blood gas partial pressures were measured in 11 animals; 10 were hypoxemic. On thoracic radiographs, the predominant pattern of pulmonary infiltration was alveolar. Symmetry of involvement, which was assessed by examining dorsoventral or ventrodorsal radiographic projections, could be determined for 23 animals. In 18, involvement was asymmetric, and in 13 of those 18, the right side was predominantly involved. On lateral radiographic projections, the caudodorsal quadrant of the lung field was involved primarily or as part of a diffuse distribution in all but 1 animal. Generally, animals with NPE resulting from airway obstruction had the greatest degree of radiographic involvement, followed in decreasing order, by animals with NPE resulting from cranial trauma, animals with NPE resulting from seizures, and animals with NPE resulting from electric shock. Overall, 9 animals died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782247 TI - Hepatic disease associated with administration of tetanus antitoxin in eight horses. AB - Seven horses developed clinical or subclinical hepatitis 48 to 87 days after administration of tetanus antitoxin. One horse had mildly high hepatic enzyme activity 120 days after inoculation with tetanus antitoxin. The first horse developed signs of depression, lethargy, and anorexia. During hospitalization, signs of hepatoencephalopathy were noticed, and laboratory data were consistent with hepatic disease. Another horse that was found dead had gross and histologic lesions compatible with serum hepatitis. Screening of serum gamma glutamyltransferase (GGT) and aspartate transaminase activities were used to investigate the remaining horses in the herd. High GGT activities (71 to 206 IU/L) were detected in 5 additional herd members. These horses appeared clinically normal, apart from 2 reports of nasal photosensitization and an aborted fetus. In 3 horses, high serum GGT activity persisted over a 44-day testing period. All affected horses had been given tetanus antitoxin within 12 hours of parturition, and a common source of vaccine was identified for 7 horses. Findings in this group of horses indicate that clinical and subclinical serum hepatitis can develop after administration of tetanus antitoxin. PMID- 7782248 TI - Arthroscopic findings in the carpal joints of lame horses without radiographically visible abnormalities: 41 cases (1986-1991). AB - Arthroscopy was performed in 1 carpal joint unilaterally in 27 horses and either in 2 carpal joints unilaterally or 1 carpal joint bilaterally in 7 horses. All horses were lame, but the cause of lameness could not be determined from radiographs. Twenty-seven carpi did not have radiographically visible abnormalities; the remaining 14 had only mild to moderate lucency or sclerosis of the radial facet of the third carpal bone. The primary abnormalities identified during arthroscopy included a crush fracture of the third carpal bone (7 carpi), an incomplete fracture of the third carpal bone in the frontal plane (13 carpi), an incomplete fracture of the third carpal bone in the sagittal plane (1 carpus), a crush fracture of the radial carpal bone (1 carpus), a chip fracture of the intermediate carpal bone (1 carpus), damage to the articular cartilage of the third carpal bone (12 carpi), tearing or fraying of the medial palmar intercarpal ligament (4 carpi), and synovitis (2 carpi). All of the horses in this study were racehorses (29 Standardbreds and 5 Thoroughbreds), and race records were used to evaluate performance before and after surgery. Twenty-four of 34 horses raced preoperatively, and 25 of 34 raced postoperatively. Twenty-three of the 27 (85%) horses in which a single joint was examined raced postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782249 TI - Prevalence of antibodies to Toxoplasma gondii in swine in Illinois in 1992. AB - A serologic survey that tested for antibodies to Toxoplasma gondii was conducted, using the modified direct agglutination test, on 6,965 serum samples collected from swine in 179 herds in Illinois in 1992. In breeding swine, results for 1,057 of 5,080 (20.8%) sera tested were positive. In growing/finishing swine, results for 59 of 1,885 (3.1%) sera tested were positive, which was substantially lower than the seroprevalence rate estimated in a serosurvey of pigs from abattoirs in Illinois in 1983 and 1984. Data in the survey reported here were summarized for herds having at least 28 samples/herd. Among all herds, the median, mean, and maximum seroprevalence rates were 6.7, 16.1, and 96.8%, respectively, for breeding swine in 172 herds, and 0.0, 2.8, and 20.0%, respectively, for growing/finishing pigs in 44 herds. Among the 172 herds with breeding swine, 61 (35.5%) had no seropositive pigs. Among the 44 herds with growing/finishing swine, 28 (63.6%) had no seropositive pigs. A logistic regression model was used to estimate that the cumulative risk of T gondii infection for swine in herds containing seropositive pigs was 9.0% by 6 months of age for a herd that had the median seroprevalence rate. In contrast, for pigs in herds in the upper quartile of seroprevalence rates, risk of infection by 6 months of age was estimated to be greater than 20%. Analysis of these data would suggest that overall prevalence of T gondii infection in pigs from Illinois is low; nevertheless, there is a small proportion of farms for which the rate of T gondii infection in swine is moderately high. PMID- 7782250 TI - Use of a type II external skeletal fixator for repair of delayed union in three calves with forelimb fractures. AB - Three calves, 3 to 6 months old, were admitted for evaluation and treatment of fractures of the forelimb that had resulted from use of forced extraction at birth. Each of these calves had clinical and radiographic evidence of delayed union of a fractured metacarpus. All calves were treated, using a type II external skeletal fixator consisting of 0.25-inch-diameter transcortical pins and acrylic connecting bars. Two calves required open reduction of the fracture to obtain anatomic alignment of the limb. On the basis of the 3 calves described here, it would appear that type II external skeletal fixators may be adequate for treatment of selected calves with delayed union of a fracture. PMID- 7782251 TI - Stationary phase induction in Escherichia coli--new targets for antimicrobial therapy? PMID- 7782252 TI - Predicting the efficacy of antimicrobial agents in respiratory infections--is tissue concentration a valid measure? AB - Despite methodological and interpretive problems associated with studies of antibiotic concentrations in tissues, it is important to confirm the presence of a drug in significant concentrations in tissues and fluids at a particular site. For antibiotics used in the treatment of community-acquired respiratory infections, tissue distribution at sites of potential infection in the respiratory tree has been related to clinical outcome. Measurement of antibiotic concentrations achieved in lung parenchyma epithelial lining fluid, bronchial mucosa or bronchial secretions has indicated significant levels for beta-lactams and macrolides. Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of macrolides, as shown in several models of phagocytic cells, and of intracellular antibacterial activities. For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactam and of macrolides should be of value. For bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides that can be achieved in extravascular and intracellular fluids should have clinical relevance, as shown in this review. Moreover with newer macrolides one may expect a better patient compliance due to prolonged persistence of drug in tissues and cells which results in shorter duration of treatment and once-daily dose administration. Finally, for some sites of infection and particularly in the human respiratory tree, there is a clear relationship between local concentrations and clinical efficacy. PMID- 7782253 TI - Evaluation of a broth microdilution antifungal susceptibility test with a pH indicator: comparison with the broth macrodilution procedures. AB - A broth microdilution antifungal susceptibility test with a pH indicator (bromocresol purple) in a synthetic medium was evaluated. This method measures cellular activity instead of simply a change in biomass. The variations of pH caused by fungal activity were measured by changes in optical densities at 450 nm. The MICs50 obtained were compared with the MICs found by the classical broth macrodilution procedure. In most cases broth micro- and macrodilution MICs were in agreement for amphotericin B, fluconazole, flucytosine and nystatin. PMID- 7782254 TI - Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide. AB - Strategies to augment conventional methods of drug delivery in treatment of multiple drug resistant tuberculosis are needed to achieve optimum results with available drugs. We have studied the effect of sub-minimum inhibitory concentrations (sub-MIC) of ethambutol and dimethyl sulphoxide on drug susceptibility of Mycobacterium tuberculosis strains both in vitro and in macrophages. At sub-MIC ethambutol between caused four and 64 fold increase in susceptibility to isoniazid rifampicin and streptomycin in four M. tuberculosis strains, resistant to these drugs. Incubation of the organisms with isoniazid and sub-MIC of dimethyl sulphoxide (2.5%) resulted in an eight-fold increase in susceptibility to the drug. Previous exposure of the organisms to sub-MIC of dimethyl sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC of sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC enhanced the activity of the anti-tuberculosis drugs against multiple drug resistant M. tuberculosis strains growing inside macrophages. Our data indicate that the agents which modify cell wall permeability can enhance the susceptibility of multiple drug resistant strains to drugs to which they were originally resistant. This could provide a new approach to treating drug resistant tuberculosis. PMID- 7782255 TI - The activity of halofuginone in immunosuppressed rats infected with Cryptosporidium parvum. AB - Halofuginone was evaluated for its activity against experimentally induced infection due to Cryptosporidium parvum in rats rendered immunosuppressed with dexamethasone. The drug's activity was dose-related and both prophylaxis and therapy reduced the rate and severity of infection in the small intestine and caecum. Prophylactic treatment reduced infection of the common bile duct, but therapeutic administration did not and neither form of treatment reduced the infection rate in the colon. Intestinal infection recurred at a level comparable to that of untreated controls when treatment was discontinued. Treatment with halofuginone may reduce the severity of acute cryptosporidiosis, but is less efficacious for chronic cryptosporidiosis involving the colon and extraintestinal tissues, a manifestation increasingly seen in the immunocompromised host. PMID- 7782256 TI - A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital personnel. AB - Sixty-eight health care workers were enrolled in a double-blind clinical trial and randomized to receive either mupirocin calcium ointment or placebo, intranasally bid for 5 days. Nasal cultures were taken immediately before starting treatment, 1 and 2 during treatment, at the end of treatment, 3 days later, weekly for 1-5 weeks and then monthly for 2-6 months after treatment. Mupirocin eliminated nasal carriage with Staphylococcus aureus in 58% of subjects within two days and 86.7% subjects by the end of therapy compared to 9.4% subjects at the end of treatment with placebo (P < 0.001). Post-treatment colonization rates of 43%, 56% and 67% were attained after 1 month, 2-4 and 6 months treatment with mupirocin respectively and recolonisation with the same strain of S. aureus that had been isolated before treatment was noted in 32%, 40% and 48%. No resistance to mupirocin developed and the drug was well tolerated. Mupirocin is safe and effective in suppressing nasal carriage of S. aureus. PMID- 7782258 TI - Susceptibility of methicillin-resistant Staphylococcus aureus to the essential oil of Melaleuca alternifolia. AB - All 66 isolates of Staphylococcus aureus tested were susceptible to the essential oil of Melaleuca alternifolia, or tea tree oil, in disc diffusion and modified broth microdilution methods. Of the isolates tested, 64 were methicillin resistant S. aureus (MRSA) and 33 were mupirocin-resistant. The MIC and MBC for 60 Australian isolates were 0.25% and 0.50%, respectively. Comparable results were obtained by co-workers in Britain using similar methods. These in-vitro results suggest tea tree oil may be useful in the treatment of MRSA carriage. PMID- 7782257 TI - Prevention of subsequent urinary tract infections in women by the use of anti adherence antimicrobial agents: a double-blind comparison of enoxacin with co trimoxazole. AB - A prospective, double-blinded crossover study was carried out to test whether a brief course of antibiotic therapy could eliminate bacteria adherent to uroepithelial cells and thus prolong the interval between urinary tract infections (UTIs). Thirty-two women with frequent Gram-negative urinary tract infections were randomized to receive either co-trimoxazole or enoxacin twice a day for 10 days to treat their UTI. Their urines were collected for 30 days after the onset of their UTI and quantitatively analyzed for bacteria, antibiotics, and bacteria adherent to uroepithelial cells (UECs). A subsequent infection caused the patient to be treated with the alternative antibiotic. A third infection terminated the study. Both regimens were indistinguishable in the rate of elimination of bacteria and in their inhibition of bacterial adherence to UECs for up to five days after stopping treatment. The interval between infections was inversely correlated with the number of adherent bacteria per UEC 30 days after the onset of the first UTI. Both regimens were equally effective in preventing subsequent UTI and the effect of 10 days therapy on the inhibition of bacterial adherence to UEC's did not extend beyond five days after stopping treatment. PMID- 7782259 TI - Comparing antimicrobial activity against resistant Pseudomonas aeruginosa using an index for the absence of cross-resistance. AB - We devised an index to estimate the degree cross-resistance between piperacillin, ceftazidime, sulbactam/cefoperazone, amikacin, tobramycin, carumonam and imipenem against 139 separate clinical isolates of Pseudomonas aeruginosa. A negative value of the index indicated the cross-resistance whereas a positive value suggested the converse making the device an index for the absence of cross resistance (ACR). Using the ACR index, we identified pairs of antibiotics exhibiting the least degree of cross-resistance and therefore the highest potential for treating infections due to P. aeruginosa. PMID- 7782260 TI - An enzymatic method for assaying sulbactam in human serum: comparison with high performance liquid chromatography. AB - An enzymatic method using nitrocefin as substrate was developed to assay sulbactam in human serum. Serum containing sulbactam was incubated with purified titrated TEM-1 beta-lactamase and nitrocefin was then added to the mixture to determine the remaining beta-lactamase activity and consequently the concentration of sulbactam. Assays were carried out on five patients with pulmonary infections receiving sulbactam plus amoxycillin iv. The values for serum sulbactam concentrations determined by the enzymatic method were compared with those determined by high performance liquid chromatography (HPLC). The correlation coefficient was 0.990 for serum sulbactam concentrations below 15 mg/L. PMID- 7782261 TI - Amoxycillin-clavulanate versus methicillin or isoxazolyl penicillins for treatment of Staphylococcus aureus infections. PMID- 7782262 TI - Sensitivity to cefotaxime of pneumococci isolated in the UK. PMID- 7782263 TI - Concentration dependence of gentamicin post-bolus peak effect on Escherichia coli kill kinetics. PMID- 7782265 TI - Usefulness of femoro(ilio)-axillar bypass surgery for the treatment of subclavian steal syndrome caused by aortitis syndrome. AB - In two patients with subclavian steal syndrome associated with aortitis syndrome, retrograde bypass grafting from the femoral or common iliac artery to the axillary artery resulted in the disappearance of symptoms. One patient, a 37-year old female, was treated with a bypass from the left femoral artery to the left axillary artery with a 10-mm ring-supported double velour knitted Dacron graft. The other patient, a 54-year-old female, with the complication of moderate aortic regurgitation, was treated with a bypass from the left common iliac artery to the left axillary artery with an 8-mm EPTFE graft. These bypass grafts were angiographically confirmed to be patent after the operation. When changes in graft flow in different body positions (supine, sitting, and standing) were examined, using a transcutaneous Doppler flow meter, 5 years after the operation, resting graft flow to the upper extremities showed no consistent changes among the three different positions and was maintained in a stable condition, regardless of the patients' positions. Furthermore, graft flow increased while the left arm exercised. This finding, together with the clinical efficacy, indicates that this mode of retrograde bypass grafting may be effective in some selected patients with this complicated syndrome. PMID- 7782264 TI - Rheological significance of tandem lesions of the coronary artery. AB - It is not known whether the individual lesions that constitute tandem lesions of the coronary artery are developmentally or rheologically related. Luminal changes and their rheological significance were examined by percutaneous angioscopy in 44 tandem lesions of 21 patients with ischemic heart disease. Angioscopically, individual narrowing of angiographically documented tandem lesions appeared only as a tangentially expressed prominent portion of an atherosclerotic spiral fold. The directions of the fold were counterclockwise in the proximal to middle segments and clockwise in the distal segment of the right coronary artery, clockwise in the proximal to middle segments and counterclockwise in the distal segment of the left anterior descending artery, and counterclockwise in the proximal to middle segments of the left circumflex artery. The bloodstream always ran along the spiral folds in the tandem lesions. The results suggest that angiographically documented tandem coronary lesions are merely a tangential expression of atherosclerotic spiral folds and that they may act to prevent blood turbulence by generating a spiral laminal flow. PMID- 7782266 TI - Cardiodynamic conditions for the linearity of preload recruitable stroke work. AB - Studies reported in the literature show that the stroke work (SW) versus end diastolic volume (Ved) relationship, namely, the preload recruitable stroke work relation (PRSW), is experimentally linear in closed-chest dog hearts and its slope reflects left ventricular contractility. We considered the theoretical cardiodynamic conditions necessary for the linearity of the SW-Ved relation by utilizing ventricular end-systolic elastance, Emax (ventricular contractility), and effective arterial elastance, Ea (arterial afterload). We simulated the SW Ved relation, using four theoretical models of the left ventricle, as follows: Ea is constant and the end-systolic pressure-volume relation (ESPVR) is linear (model 1), or nonlinear (model 2), and Ea is variable and ESPVR is linear (model 3), or nonlinear (model 4). The results show that the SW-Ved relation can be linear in both linear and nonlinear ESPVR models (models 3 and 4) only when Ea is variable. In these models, end-systolic pressure (Pes) and Ea should gradually fall, maintaining the stroke volume (SV) relatively constant with decreases in Ved until the low end of the physiological Ved range. Then, Ea should rise sharply so that Pes does not fall below the critical level. These results suggest that the autoregulation mechanisms of an intact animal operate to adapt the arterial afterload against acute changes in LV preload, maintaining cardiac output and coronary artery pressure. Such mechanisms may thus produce a linear SW Ved relation over a wide range of conditions. PMID- 7782267 TI - Regional myocardial function curve of the ventricle. AB - To understand the pathophysiology of diseased hearts, we devised a new regional myocardial function curve and investigated its properties. Regional work per unit volume of the myocardium (RWM) was calculated by integrating mean wall stress (sigma) with respect to the natural logarithm of the reciprocal of wall thickness [ln(1/H)] over a cardiac cycle. Regarding the end-diastolic ln(1/H) as the preload for the region of concern on the assumption that the myocardium is incompressible, we defined the relation between RWM and end-diastolic ln(1/H) as the regional myocardial function curve. In ten mongrel dogs, we measured left ventricular pressure, left ventricular internal diameter, and wall thickness with a catheter-tip micromanometer and ultrasonic dimension gauges during volume loading to obtain the regional myocardial function curve. We examined the sensitivity of the regional myocardial function curve to changes in contractile state (isoproterenol, propranolol) and changes in afterload (pressure loading by a balloon-occlusion catheter). The linear fit to the data points of the regional myocardial function curve under each condition always achieved a very good correlation coefficient (greater than 0.62). Isoproterenol increased the slope of the regional myocardial function curve from 9.7 +/- 0.9 (SEM) mJ/cm3 to 14.4 +/- 1.0 mJ/cm3 (P < 0.01), with no significant changes in the x-intercept, while propranolol decreased it to 5.6 +/- 1.2 mJ/cm3 (P < 0.01) with no significant changes in the x-intercept.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782268 TI - Acute effects of amiodarone on membrane properties, refractoriness, and conduction in guinea pig papillary muscles. AB - Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 microM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (Vmax) of the fast action potential (i.e., [K]e = 5.4-9.0 mM) as well as that of the slow action potential (i.e., [K]e = 15.0 mM in the presence of 1.0 microM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]e dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD90), disclosing post repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug. PMID- 7782269 TI - Regional diastolic function in effort angina pectoris: assessment with biplane left ventriculography. AB - To investigate left ventricular (LV) regional diastolic function in effort angina pectoris (AP), we performed left ventriculography in 14 patients with AP and isolated left anterior descending artery disease and in 9 normal subjects (N). LV volume (V), regional area (S) [anterior, apex, and inferior], and the first derivative of V and S (dV/dt, dS/dt) were derived from analysis of the left ventriculogram. Normalized peak filling rate (nPFR) and peak atrial filling rate (nPAFR) were derived from dV/dt. The ratio of filling volume to stroke volume during rapid filling and atrial contraction were defined as rapid filling fraction (RFF) and atrial filling fraction (AFF). Similarly, peak area changing rate (PACR), peak area changing rate during atrial contraction (PACRac), rapid area changing fraction (RACF), and atrial area changing fraction (AACF) were derived from S and dS/dt. We also calculated the time constant of LV relaxation (T), and LV global and regional compliance during atrial contraction [(dV/VdP)ac, (dS/SdP)ac]. The LV global diastolic function (T increases, nPFR decreases) was impaired in the angina patients. LV regional diastolic function (nPACR decreases, RACF decreases) was also impaired in the affected region of the AP group. While their rapid filling was impaired, nPACRac was maintained and AACF was increased in the affected region. Furthermore, nPACR and RACF each showed a significant inverse correlation with AACF in the anterior region [r = -0.57 (P < 0.01), r = 0.92 (P < 0.001)]. In the affected region of the patients with AP, (dS/SdP)ac was increased, but not significantly. Thus, LV global and regional diastolic functions were simultaneously impaired in patients with isolated left anterior descending artery disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782271 TI - The impact of health care reform on social phobia. AB - According to the National Comorbidity Survey, social phobia is the third most frequent psychiatric disorder in the United States. Its lifetime prevalence rate of 13.3% ranks behind only major depressive episode (17.1%) and alcohol dependence (14.1%). As was the case with depression 15 years ago, social phobia has often been trivialized and stigmatized. For example, some with social phobia may be dismissed as having mere "stage fright" or excessive shyness, while, in fact, social phobia is a serious mental illness associated with substantial psychosocial distress, comorbidity, and morbidity. Typical onset of social phobia is in the midteens and often continues throughout an individual's lifetime, leading to severe social and occupational impairment. Several excellent, efficacious treatments are available. Access to these treatments for social phobia may be more difficult in the future due to managed care initiatives and health care reform. Various proposals are now being considered as a part of health care reform that may have significant impact on the diagnosis and treatment of social phobia. PMID- 7782272 TI - Social phobia: a pharmacologic treatment overview. AB - Generalized and specific social phobias are common, chronic, and potentially debilitating conditions. In recent years, there have been major advances in the pharmacotherapy of social phobia; efficacy has become better established for a diverse group of medications. Controlled studies have shown substantial benefit from monamine oxidase inhibitors, both irreversible (phenelzine) and reversible (brofaromine and moclobemide). The serotonin selective reuptake inhibitor antidepressants have shown promise in case reports, uncontrolled studies, and double-blind trials (fluvoxamine and sertraline). The benzodiazepines have been extensively used to treat social phobia, although only recently has a controlled, double-blind study confirmed efficacy (clonazepam). The beta-adrenergic receptor blockers have been widely used on an as needed basis to treat specific social phobia (i.e., performance anxiety), although their value in generalized social phobia has not been convincing. Finally, pharmacologic approaches to social phobia must take into consideration the common coexistence of other psychiatric conditions. PMID- 7782273 TI - Advances in behavioral-cognitive therapy of social phobia. AB - Behavioral-cognitive therapy is a cost-effective treatment for social phobia. The doctor's role is to teach the patient how to do successful self-exposure. The clinician acts as a guide and monitor; there is no need to waste time accompanying the patient into the phobic situation. The patient first reads a self-exposure manual to learn how to confront panic-evoking social cues for prolonged period without avoidance until habituation sets in. This might require an hour daily of self-exposure over weeks or months. As patients habituate to social cues to which they have exposed themselves, they arrange exposure to fresh cues until they become used to all. The patient tracks progress by recording completed exposure-homework tasks in a daily diary. In instances where it is technically difficult to do regular exposure, the patient carries out imagined tape-recorded exposure in his/her own voice. The therapist can briefly help the patient role-play such exposure. Rational role-play enhances outcome of body dysmorphic disorder or delusional disorder somatic type with prominent social phobia. Cognitive therapy can be useful. Most social phobics improve with behavioral-cognitive treatment without medication. When patients have low mood, concurrent antidepressants can be synergistic. PMID- 7782270 TI - Sonicated X-ray contrast agents for quantitative myocardial contrast echocardiography--a critical approach. AB - Contrast echocardiography with sonicated radiographic contrast agents has been used for the qualitative and quantitative determination of myocardial blood flow. One major problem has been the size of the microbubbles since only bubbles smaller than 8 microns are expected to pass the capillary bed and larger bubbles may obstruct the capillaries and, thus, alter myocardial blood flow. These techniques have been used for several years, but their reliability has not yet been assessed accurately. Five different methods for the production of sonicated radiographic contrast agents (methods 1-3 from the literature, and 4 and 5 from our laboratory; M1-5) were evaluated for their use in quantitative contrast echocardiography. The sonication of non-ionic X-ray contrast media was performed with a standard titanium probe (20 kHz) for methods 1-4, with variation in the sonication time and the number of sonication jets used for each method. In M5, we used bubbles that were produced by the insufflation of oxygen in the X-ray contrast agent; large (> 8 microns) bubbles were destroyed by sonication at 380 kHz (resonance method). Mean bubble size was determined by computerized videomicroscopy. The effect of bubble size on the backscatter of the ultrasonic signal was calculated for each method. Mean bubble size (+/- 1 SD) ranged between 11.5 +/- 4 microns and 16.1 +/- 14 microns for M1-M5. The best values, i.e., the smallest bubbles, were found with M4 (prepressurized contrast medium). Assuming capillary passage for bubbles smaller than 8 microns, only 14%-48% of the bubbles were smaller than 8 microns (M1-M5). The best results with regard to bubble size (< or = 8 microns) were observed with M5 (48% < or = 8 microns). In regard to the influence of bubble size on the backscatter of the ultrasonic signal, 56%-98.5% of the signal was produced by bubbles larger than 15 microns (M1-5) but the best results were obtained with M4. It is concluded that capillary-passage of sonicated microbubbles (< or = 8 microns) can be expected in only 14%-48% of the bubbles for the five different sonication techniques. More than 50% of all microbubbles produced by these techniques are larger than the expected 8 microns. These large bubbles are responsible for the backscatter of the ultrasonic signal in the vast majority of cases. Thus, the sonication of radiographic contrast agents appears to be inappropriate for the production of uniformly small microbubbles and, thus, this method is not suitable for quantitative measurements of coronary blood flow. PMID- 7782274 TI - The diagnosis of social phobia. AB - Humans are social animals attuned to reactions of others; however, some are exquisitely sensitive to--and often misperceive--perceptions of those they encounter. The core feature of social phobia is marked and persistent fear of embarrassment or humiliation in social situations where the individual worries that others may judge his or her performance as too much or too little. Anticipatory anxiety and avoidance occur when the individual is under scrutiny while speaking or performing publicly, eating with others, writing in public, or using public bathrooms. Diagnosis of social phobia is based largely on history obtained from the patient. Onset is usually around puberty; its course is chronic with comorbid depression common and alcohol and other substances routinely abused in misguided attempts to minimize anxiety and depressive symptoms. At examination, patients often have a moist hand, averted gaze, blushing, and other manifest signs of anxiety. Slight shyness is familiar to most, but a substantial number suffer dysfunctional and distressing social anxiety to the point that they become phobic. A few patients satisfy criteria for avoidant personality disorder, which can be socially incapacitating. PMID- 7782275 TI - I-type lectins. PMID- 7782276 TI - Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain. AB - The receptor-like protein tyrosine phosphatases (RPTP) mu and RPTP kappa have a modular ectodomain consisting of four fibronectin type III-like repeats, a single Ig-like domain, and a newly identified N-terminal MAM domain. The function of the latter module, which comprises about 160 amino acids and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions. PMID- 7782277 TI - A direct interaction between G-protein beta gamma subunits and the Raf-1 protein kinase. AB - Raf-1 is a serine/threonine protein kinase positioned downstream of Ras in the mitogen-activated protein kinase cascade. Using a yeast two-hybrid strategy to identify other proteins that interact with and potentially regulate Raf-1, we isolated a clone encoding the carboxyl-terminal half of the G beta 2 subunit of heterotrimeric G-proteins. In vitro, purified G beta gamma subunits specifically bound to a GST fusion protein encoding amino acids 1-330 of Raf-1 (Raf/330). Binding assays with truncation mutants of GST-Raf indicate that the region located between amino acids 136 and 239 is a primary determinant for interaction with G beta gamma. In competition experiments, the carboxyl terminus of beta adrenergic receptor kinase (beta ARK) blocked the binding of G beta gamma to Raf/330; however, the Raf-1-binding proteins, Ras and 14-3-3, had no effect. Scatchard analysis of in vitro binding between Raf/330 and G beta gamma revealed an affinity of interaction (Kd = 163 +/- 36 nM), similar to that seen between G beta gamma and beta ARK (Kd = 87 +/- 24 nM). The formation of native heterotrimeric G alpha beta gamma complexes, as measured by pertussis toxin ADP ribosylation of G alpha, could be disrupted by increasing amounts of Raf/330, with an EC50 of approximately 200 nM, in close agreement with the estimated binding affinity. In vivo complexes of Raf-1 and G beta gamma were isolated from human embryonic kidney 293-T cells transfected with epitope-tagged G beta 2. The identification and characterization of this novel interaction raises several possibilities for signaling cross-talk between growth factor receptors and those receptors coupled to heterotrimeric G-proteins. PMID- 7782279 TI - Rhodopsin phosphorylation and dephosphorylation in vivo. AB - Rhodopsin is an important member of the superfamily of G protein-coupled receptors. In vitro studies have suggested that multiphosphorylation of rhodopsin is a pivotal step in phototransduction. Because the in vitro biochemical experiments were conducted under nonphysiological conditions, we investigated the phosphorylation of mouse rhodopsin in vivo and determined the sites of phosphorylation and the time course of dephosphorylation. We found that a single phosphate group is incorporated into the rhodopsin molecule in a light-dependent manner, primarily at Ser338 after flashes and at Ser334 after continuous illumination. Dephosphorylation of these sites had different kinetics and spatial distribution in rod outer segments. Dephosphorylation of Ser338 was complete within 30 min, while Ser334 was dephosphorylated much slower (requiring up to 60 min), correlating with the regeneration of rhodopsin. These results suggest that phosphorylation of Ser338 and Ser334 plays different roles in phototransduction. PMID- 7782278 TI - Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. AB - To control agonist-induced nuclear translocation of transcription factor kappa B (NF-kappa B) in intact cells, cell-permeable synthetic peptides were devised. Their import into intact cells was dependent on a hydrophobic region selected from the signal peptide sequences and was verified by their inaccessibility to extracellular proteases and by confocal laser scanning microscopy. When a cell permeable peptide carried a functional cargo representing the nuclear localization sequence of NF-kappa B p50, it inhibited in a concentration dependent manner nuclear translocation of NF-kappa B in cultured endothelial and monocytic cells stimulated with lipopolysaccharide or tumor necrosis factor alpha. Synthetic peptide analogues with deleted hydrophobic cell membrane permeable motif or with a mutated nuclear localization sequence were inactive. Cell membrane-permeable peptides were not cytotoxic within the concentration range used in these experiments. These results suggest that cell-permeable synthetic peptides carrying a functional cargo can be applied to control signal transduction-dependent subcellular traffic of transcription factors mediating the cellular responses to different agonists. Moreover, this approach can be used to study other intracellular processes involving proteins with functionally distinct domains. PMID- 7782280 TI - A sphingomyelin-transferring protein from chicken liver. Use of pyrene-labeled phospholipid. AB - A phospholipid transfer protein was purified from chicken liver which, in addition to phosphatidylinositol (PI) and phosphatidylcholine (PC), carries sphingomyelin (SM) between membranes. For comparison, the PI-transfer protein from chicken liver only carries PI and PC. Specificity was established by use of phospholipids that carry a pyrene-labeled acyl chain. Based on the N-terminal sequence and Western blot analysis we conclude that this protein is an isoform of the PI-transfer protein. At increasing length of the pyrene-labeled acyl chain, the isoform expresses a high activity toward SM, a low activity toward PI, and virtually no activity toward PC. PMID- 7782281 TI - Import of the cytochrome oxidase subunit Va precursor into yeast mitochondria is mediated by the outer membrane receptor Mas20p. AB - Post-translational import of precursor proteins into yeast mitochondria is mediated by at least four protease-sensitive outer membrane proteins: Mas20p, Mas22p, Mas37p, and Mas70p. These "import receptors" recognize either the N terminal targeting signal or some other feature of mitochondrial precursor proteins. The only exception to this general rule appeared to be the precursor to subunit Va of cytochrome c oxidase (COXVa). Although this precursor carries a typical N-terminal mitochondrial targeting sequence, its import into mitochondria has been suggested to be independent of the known import receptors. Here we show that if import into isolated yeast mitochondria is assayed under conditions in which binding of the COXVa precursor to mitochondria is rate-limiting, import is strongly inhibited by protease pretreatment of the mitochondria or by antibodies against Mas20p. Post-translational import of the COXVa precursor can thus proceed by the general, receptor-mediated pathway. PMID- 7782282 TI - Molecular mapping of functional antibody binding sites of alpha 4 integrin. AB - Integrin alpha 4 beta 1 is a leukocyte receptor for fibronectin and vascular cell adhesion molecule-1 (VCAM-1). It is important in inflammatory recruitment of leukocytes, lymphopoiesis, and a number of development events. Here we have mapped a panel of functional monoclonal antibodies (mAbs) recognizing the integrin alpha 4 chain, using murine/human chimeric constructs expressed in COS7 cells. We find that: 1) mAbs that induce homotypic aggregation (epitope A mAbs) map to the most N-terminal 100 amino acids of the human alpha 4 chain; 2) mAbs that block adhesion of alpha 4 beta 1 to VCAM-1 and fibronectin (epitope B mAbs) map to a 52-amino-acid region between residues 152 and 203 of human alpha 4; 3) epitope B mAbs that do or do not induce aggregation (epitope B2 and B1 mAbs, respectively) map to the same regions and are therefore indistinguishable by this analysis; 4) mAbs that neither induce homotypic aggregation nor block adhesion (epitope C mAbs) map to a distinct region of the molecule comprising amino acids 422-606. The N-terminal region of the alpha 4 chain identified by functional A and B epitope mAbs does not correspond to ligand binding sites identified in other alpha subunits, such as cation binding sites or the "I-domain," which alpha 4 lacks, and thus represents a novel site for epitope functionality among the integrins. PMID- 7782283 TI - Ligand-independent and -dependent functions of thyroid hormone receptor isoforms depend upon their distinct amino termini. AB - Isoform specificity likely plays a large role in the ability of the thyroid hormone receptor (TR) to specifically regulate gene expression in both the presence and absence of its cognate ligand, triiodothyronine. To investigate further the mechanism of isoform specificity of human TRs (TR alpha 1 and TR beta 1), we have examined their functional effects on positive thyroid hormone response elements (TREs) both in the presence and absence of ligand. TR alpha 1 was greater than 2-fold more potent than TR beta 1 on both TREs studied, in terms of both ligand-independent repression and ligand-dependent stimulation. By creating a number of chimeric and mutant receptors, we have established that the increased functional potency of TR alpha 1 is due to its unique amino terminus. Deletion or substitution of the TR alpha 1 amino terminus leads to a loss of both its ligand-independent and -dependent functions on positive TREs. Furthermore, the TR alpha 1 amino terminus antagonizes homodimer formation on the positive TREs studied. TR constructs, which contain the TR alpha 1 amino terminus, are unable to form homodimers and form exclusively heterodimers with RXR alpha on direct repeat and palindromic TREs. Deletion of the amino terminus from either TR isoform leads to preferential homodimer formation, which suggests that the TR amino terminus is important for relative heterodimerization capability. From these data, we conclude that TR alpha 1 isoform specificity on positive TREs resides predominantly in its amino terminus through its ability to favor heterodimerization with the retinoid X receptor or other nuclear proteins. PMID- 7782284 TI - A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia. AB - The microsomal triglyceride transfer protein (MTP) is a heterodimer composed of the multifunctional enzyme, protein disulfide-isomerase, and a unique large, 97 kDa, subunit. It is found as a soluble protein within the lumen of the endoplasmic reticulum of liver and intestine and is required for the assembly of very low density lipoproteins and chylomicrons. Mutations in MTP which result in an absence of MTP function have been shown to cause abetalipoproteinemia. Here, the gene encoding the MTP 97-kDa subunit of an abetalipoproteinemic subject, which we have previously demonstrated lacks MTP activity and protein (Wetterau, J. R., Aggerbeck, L. P., Bouma, M.-E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D. J., and Gregg, R. E. (1992) Science 258, 999 1001), was isolated and sequenced. A nonsense mutation, which predicts the truncation of the protein by 30 amino acids, was identified. To investigate if this apparently subtle change in MTP could explain the observed absence of MTP, protein disulfide-isomerase was co-expressed with either the normal or mutant MTP 97-kDa subunit in Sf9 insect cells using a baculovirus expression system. Although there were high levels of expression of both the normal and mutant forms of the MTP 97-kDa subunit, only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase. These results indicate that the carboxyl-terminal 30 amino acids of the MTP 97-kDa subunit plays an important role in its interaction with protein disulfide-isomerase. PMID- 7782285 TI - Characterization of the binding site for cyclothialidine on the B subunit of DNA gyrase. AB - The mechanism of inhibition of DNA gyrase by cyclothialidine, a novel gyrase inhibitor isolated from Streptomyces filipinensis NR0484, has been studied further by using [14C]benzoylcyclothialidine and a reconstituted Escherichia coli gyrase system consisting of the A subunit, the B subunit and relaxed ColE1 DNA. The mechanism of inhibition was also studied with the 43-kDa N-terminal fragment of the B subunit. The [14C]benzoylcyclothialidine could bind to the B subunit alone but not to the A subunit nor to the plasmid DNA alone. Furthermore, the compound also bound to the 43-kDa N-terminal fragment of the B subunit. Scatchard analysis of [14C]benzoylcyclothialidine binding to DNA gyrase showed that the binding affinity of the compound increased, depending on the assembly of the gyrase (A2B2). DNA complex. This suggests that the binding site of cyclothialidine on the B subunit or its vicinity causes a conformational change during the assembly of the gyrase.DNA complex (increase in affinity: B-->A2B2- >A2B2.DNA). Furthermore, displacement curves of [14C]benzoylcyclothialidine binding by nonlabeled cyclothialidine, ATP analogues, and coumarin antibiotics indicated that cyclothialidine, coumarins, and ATP share a common (or overlapping) site of action on the B subunit of DNA gyrase; however, the microenvironment of the binding sites may differ. PMID- 7782286 TI - Identification of the region within the neuroendocrine polypeptide 7B2 responsible for the inhibition of prohormone convertase PC2. AB - The highly conserved polypeptide 7B2 and the subtilisin-related prohormone convertases PC1/PC3 and PC2 are broadly distributed in neurons and endocrine cells and are localized to secretory granules. We recently showed that recombinant 7B2 is in vitro a potent inhibitor of PC2 activity, but not of PC1/PC3, and that newly synthesized 7B2 is transiently associated with proPC2 in vivo. In the present study, in vitro mutagenesis was used to identify the region within the 7B2 sequence responsible for the inhibition of PC2. Mutant proteins were produced in a prokaryotic expression system and their effects on PC1/PC3 and PC2 activities were studied by two different in vitro enzyme assays. None of the 7B2 mutant proteins inhibited PC1/PC3 activity. Truncation studies revealed that a short segment within the COOH-terminal portion of 7B2 is critical for its inhibitory effect on PC2. This segment contains a pair of basic amino acid residues which may represent a recognition motif for PC2. Single amino acid substitutions within this Lys171-Lys172 site strongly diminished and a double mutation abolished the inhibitory potency of 7B2. Our results indicate that, although amino acid residues directly surrounding this dibasic pair also contribute to PC2 inhibition, the Lys171-Lys172 site is particularly important for the ability of 7B2 to inhibit PC2. PMID- 7782287 TI - Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. AB - Mammalian pyruvate dehydrogenase (alpha 2 beta 2) (E1) is regulated by phosphorylation-dephosphorylation, catalyzed by the E1-kinase and the phospho-E1 phosphatase. Using site-directed mutagenesis of the three phosphorylation sites (sites 1, 2, and 3) on E1 alpha, several human E1 mutants were made with single, double, and triple mutations by changing Ser to Ala. Mutation at site 1 but not at sites 2 and/or 3 decreased E1 specific activity and also increased Km values for thiamin pyrophosphate and pyruvate. Sites 1, 2, and 3 in the E1 mutants were phosphorylated either individually or in the presence of the other sites by the dihydrolipoamide acetyltransferase-protein X-E1 kinase indicating a site independent mechanism of phosphorylation. Phosphorylation of each site resulted in complete inactivation of the E1. However, the rates of phosphorylation and inactivation were site-specific. Sites 1, 2, and 3 were dephosphorylated either individually or in the presence of the other sites by the phospho-E1-phosphatase resulting in complete reactivation of the E1. The rates of dephosphorylation and reactivation were similar for sites 1, 2, and 3, indicating a random dephosphorylation mechanism. PMID- 7782288 TI - Multiple transcripts for the human cardiac form of the cGMP-inhibited cAMP phosphodiesterase. AB - cDNAs for two distinct Type III cGMP-inhibited (cGI) cyclic nucleotide phosphodiesterases (PDE), designated cGIP1 and cGIP2, were previously cloned from rat adipose and human cardiac cDNA libraries, respectively. In this study, another cDNA (approximately 4.0 kilobase (kb)) encoding a cGI-PDE of 74 kDa (658 amino acids) was isolated from a human placental cDNA library. The nucleotide sequence of its open reading frame was virtually identical to a corresponding region in the 3' portion of the cardiac cGIP2 cDNA (approximately 7.6 kb) which encoded a approximately 125-kDa cGI-PDE (1141 amino acid). Northern blots and RNase protection assays revealed a prominent 4.4-kb transcript and a 7.6-kb transcript in human placenta. The transcription start site of the 4.4-kb transcript was assigned to cardiac cDNA nucleotide 1292, the putative beginning of exon 3 of the human cGIP2 gene, with a potential translation initiation site 183 bases downstream, as determined by RNase protection assay. The 5'-flanking region of the 4.4-kb transcript exhibited promoter activity in HeLa cells which expressed the 4.4-kb transcript, and contained a TATAA sequence 35 base pairs upstream from the tentative transcription start site. Recombinant cGI-PDEs, expressed in Sf9 cells from the 7.6- and 4.0-kb cDNA, exhibited differences in their subcellular localization and Km for cGMP. Thus, in human tissues, alternative transcription may contribute to generating at least two cGIP2 isoforms, cytosolic and membrane-associated cGI-PDEs with different Km values for cGMP. PMID- 7782289 TI - The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. AB - Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a critical role in extracellular matrix homeostasis. We have previously cloned human and mouse TIMP-3 cDNAs and mapped their chromosomal loci (Apte, S. S., Mattei, M-G., and Olsen, B. R. (1994) Genomics 19, 86-90; Apte, S. S., Hayashi, K., Seldin, M. F., Mattei, M-G., Hayashi, M., and Olsen, B. R. (1994) Dev. Dynam. 200, 177-197); the identification of TIMP3 mutations in Sorsby's fundus dystrophy has underscored the functional importance of TIMP-3. We now report that TIMP-3 is encoded by five exons spanning over 30 kilobase pairs of mouse genomic DNA. In the attribution of protein domains to specific exons, as well as exon structures, the Timp-3 and Timp-1 genes are similar, confirming the common evolutionary origin of the TIMPs and defining a distinct gene family. We have expressed human and mouse TIMP-3 in mouse NSO myeloma cells. In each case, an N-glycosylated 27-kDa protein was generated, that, like TIMP-1 and TIMP-2, inhibited collagenase-1, stromelysin-1, and gelatinases A and B. TIMP-3 and TIMP 1 inhibition were quantitatively similar, implying that all TIMPs are equally efficient in MMP inhibition. Instead, differential regulation of the TIMP genes or divergent C-terminal protein sequences may underlie distinct biological functions for each TIMP. PMID- 7782290 TI - An effector site that stimulates G-protein GTPase in photoreceptors. AB - Heterotrimeric G-proteins mediate between receptors and effectors, acting as molecular clocks. G-protein interactions with activated receptors catalyze the replacement of GDP bound to the alpha-subunit with GTP. alpha-Subunits then modulate the activity of downstream effectors until the bound GTP is hydrolyzed. In several signal transduction pathways, including the cGMP cascade of photoreceptor cells, the relatively slow GTPase activity of heterotrimeric G proteins can be significantly accelerated when they are complexed with corresponding effectors. In the phototransduction cascade the GTPase activity of photoreceptor G-protein, transducin, is substantially accelerated in a complex with its effector, cGMP phosphodiesterase. Here we characterize the stimulation of transducin GTPase by a set of 23 mutant phosphodiesterase gamma-subunits (PDE gamma) containing single alanine substitutions within a stretch of the 25 C terminal amino acid residues known to be primarily responsible for the GTPase regulation. The substitution of tryptophan at position 70 completely abolished the acceleration of GTP hydrolysis by transducin in a complex with this mutant. This mutation also resulted in a reduction of PDE gamma affinity for transducin, but did not affect PDE gamma interactions with the phosphodiesterase catalytic subunits. Single substitutions of 7 other hydrophobic amino acids resulted in a 50-70% reduction in the ability of PDE gamma to stimulate transducin GTPase, while substitutions of charged and polar amino acids had little or no effect. These observations suggest that the role of PDE gamma in activation of the transducin GTPase rate may be based on multiple hydrophobic interactions between these molecules. PMID- 7782291 TI - Regulation of the tertiary structure and function of coagulation factor IX by magnesium (II) ions. AB - The indispensable role of Ca2+ ions in the maintenance of the functional tertiary structures of vitamin K-dependent coagulation factors has been definitively established but the participation of Mg2+ ions, another alkaline-earth metal that is present abundantly in blood plasma, in such a process is not yet understood. We show here that the Ca(2+)-stabilized conformation of coagulation factor IX undergoes a further conformational change upon binding of Mg2+ ions using three independent structural probes. The probes we used were (i) IX/X-bp, a snake venom anticoagulant that recognizes the Gla domains in coagulation factors IX and X, (ii) conformation-specific polyclonal antibodies against bovine factor IX, and (iii) monoclonal antibodies against the Gla domain of human factor IX. The binding of all these probes had an absolute requirement for Ca2+ ions, and Mg2+ ions alone were ineffective. However, when added together with Ca2+ ions, Mg2+ ions at physiological concentrations greatly augmented the binding of these probes to factor IX; the required concentration of Ca2+ ions was much reduced, and the affinity of each probe for factor IX was increased even in the presence of an excess of Ca2+ ions. These results suggest the presence of a Mg(2+) specific binding site that does not interact with Ca2+ ions in factor IX. Furthermore, Mg2+ ions potentiated the susceptibility of factor IX to activation by factor XIa, concomitant with their effect on the conformation. Similarly, the required Ca2+ concentration was reduced by Mg2+ ions, and the rate of conversion to factor IXa was increased by Mg2+ ions in the presence of an excess of Ca2+ ions. At a saturating concentration of Ca2+ ions (5 mM), addition of 1 mM Mg2+ reduced the apparent Km value for factor IX from 0.31 to 0.18 microM, and in the presence of a physiological concentration of Ca2+ ions (1 mM), the reduction in Km by Mg2+ ions was far more striking (from 0.91 to 0.24 microM). The apparent Vmax values were hardly affected by Mg2+ ions. Our present data reveal a hitherto novel physiological role of the Mg2+ ions in plasma. Not only Ca2+ ions but also Mg2+ ions are important regulators of the stabilization of the native conformation of factor IX as well as of its efficient activation. PMID- 7782292 TI - A cytoplasmic region of the Na,K-ATPase alpha-subunit is necessary for specific alpha/alpha association. AB - While most structural studies of the Na,K-ATPase support a subunit stoichiometry of one alpha-subunit to one beta-subunit, the exact quaternary structure of the Na,K-ATPase and its relevance to enzyme function is the subject of much debate. Formation of a higher order enzyme complex is supported by our previous study demonstrating specific alpha/alpha interactions among the rat Na,K-ATPase isoforms (alpha 1, alpha 2, alpha 3), expressed in virally infected Sf-9 insect cells and among native alpha isoforms in rat brain (1). This detergent-resistant association was not observed in insect cells coexpressing the homologous gastric H,K-ATPase alpha-subunit, nor was it dependent on the coexpression of the beta subunit. To delineate domains necessary for alpha/alpha assembly, a series of H,K ATPase-Na, K-ATPase chimerase were constructed by combining the N-terminal, cytoplasmic midregion and C-terminal segments derived from the Na,K-ATPase (N) and the H,K-ATPase (H) alpha-polypeptides (HNN, HNH, NHH, NHN, and HHN). The alpha-subunit chimeras were coexpressed with the Na,K-ATPase alpha 1-subunit in Sf-9 cells using the baculovirus expression system. Specific and detergent-stable association is observed between the Na,K-ATPase alpha-subunit and the HNN and HNH chimeras, but not with the NHH, NHN, or HHN chimeras. Consistent with the Na,K ATPase cytoplasmic domain as being necessary for alpha/alpha interactions, the full-length alpha-subunit stably associates with an alpha N-terminal deletion mutant (delta Gly2-Leu273), but not with an alpha cytoplasmic deletion mutant (delta Arg350-Pro785). In addition, the naturally occurring C-terminal truncated alpha 1 isoform, alpha 1T (delta Gly554 to C terminus), does not associated with the alpha 1-subunit in Sf-9 cells coexpressing both polypeptides. thus, a cytoplasmic region in the alpha-subunit (Gly554-Pro785) is necessary for specific alpha/alpha association. The same cytoplasmic region contains a strongly hydrophobic segment that, by analogy with oligomerization of water-soluble proteins, may form the interface of the extramembranous alpha/alpha contact site. PMID- 7782293 TI - Voltage-sensitive adenylyl cyclase activity in cultured neurons. A calcium independent phenomenon. AB - Catalytic subunits of mammalian adenylyl cyclases have been proposed to contain 12 transmembrane domains, a property shared with some voltage-sensitive ion channels. Here we report that adenylyl cyclase activity in cerebellar neurons is synergistically stimulated by depolarizing agents and beta-adrenergic receptor activation. This phenomenon is Ca(2+)-independent and not attributable to Ca(2+) stimulated adenylyl cyclase activity. Cholera toxin and forskolin also synergistically stimulate adenylyl cyclase activity in combination with depolarizing agents. We hypothesize that conformational changes in the catalytic subunit of the enzymes caused by changes in the membrane potential may enhance stimulation of adenylyl cyclases by the guanylyl nucleotide stimulatory protein. This novel mechanism for regulation of adenylyl cyclases generates robust cAMP signals that may contribute to various neuromodulatory events including some forms of neuroplasticity. PMID- 7782294 TI - Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways. AB - The c-cbl protooncogene product (c-Cbl) is a 120-kDa protein that has been shown to bind to the Src homology 3 domains of various proteins, suggesting its involvement in signal transduction pathways. We identified one of the most prominent tyrosine-phosphorylated proteins in Fc gamma receptor (Fc gamma R) stimulated macrophages to be c-Cbl. Tyrosine phosphorylation of c-Cbl occurred within 20 s after stimulation and reached maximum levels within 3-5 min. c-Cbl was also tyrosine-phosphorylated in epidermal growth factor (EGF) receptor overexpressing cells upon EGF stimulation, in macrophages in response to CSF-1 treatment, and in v-src transformed cells. Furthermore, we found that c-Cbl associated with these kinases in vivo. In vitro, c-Cbl bound to the Src homology 3 domains of Src, Fyn, and Lyn in both unstimulated and Fc gamma R-stimulated macrophages. Examination of cells by immunofluorescence revealed that c-Cbl is diffusely distributed in the cytoplasm in both unstimulated macrophages and EGF receptor-overexpressing cells and translocated to a more specific compartment of the cell, consistent with the trans-Golgi region, following Fc gamma R clustering and EGF stimulation, respectively. These results suggest that c-Cbl is involved in the signaling pathways utilized by different types of tyrosine kinases. PMID- 7782295 TI - Developmentally expressed Ca(2+)-sensitive adenylyl cyclase activity is disrupted in the brains of type I adenylyl cyclase mutant mice. AB - The type I Ca(2+)-sensitive adenylyl cyclase has been implicated in several forms of synaptic plasticity in vertebrates. Mutant mice in which this enzyme was inactivated by targeted mutagenesis show deficient spatial memory and altered long term potentiation (Wu, Z. L., Thomas, S. A., Villacres, E. C., Xia, Z., Simmons, M. L., Chavkin, C., Palmiter, R. D., and Storm, D. R. (1995) Proc. Natl Acad Sci. U. S. A. 92, 220-224). Long term potentiation in the CA1 region of the rat hippocampus develops during the first 2 weeks after birth and reaches maximal expression at postnatal day 15 with a gradual decline at later stages of development. Here we report that Ca(2+)-stimulated adenylyl cyclase activity in rat hippocampus, cerebellum, and cortex increases significantly between postnatal days 1-16. This increase appears to be due to enhanced expression of type I adenylyl cyclase rather than type VIII adenylyl cyclase, the other adenylyl cyclase that is directly stimulated by Ca2+ and calmodulin. Type I adenylyl cyclase mRNA in the hippocampus increased 7-fold during this developmental period. The developmental expression of Ca(2+)-stimulated adenylyl cyclase activity in mouse brain was attenuated in mutant mice lacking type I adenylyl cyclase. Changes in expression of the type I adenylyl cyclase during the period of long term potentiation development are consistent with the hypothesis that this enzyme is important for neuroplasticity and spatial memory in vertebrates. PMID- 7782296 TI - Energetics of leukocyte integrin activation. AB - Cell adhesion mediated by leukocyte integrin CR3 (CD11b/CD18, alpha m beta 2) may be rapidly modulated without changes in receptor number, and transient changes in adhesivity are thought to be driven by reversible alteration of the affinity of CR3 for ligand. Here we measure the binding affinity of CR3 using purified active and inactive receptor and the ligand, C3bi, coupled to alkaline phosphatase. Immobilized, active CR3 bound saturably and with high affinity (12.5 +/- 4.7 nM). In contrast, inactive CR3 exhibited no measurable binding. High affinity binding could be restored by the addition of the activating anti-CR3 monoclonal antibody KIM-127 to inactive CR3. Since the affinity of KIM-127 for active and inactive receptor was identical, it cannot contribute the energy to convert a low affinity receptor into a high affinity receptor. Rather, KIM-127 appears to facilitate binding of C3bi by lowering the activation energy for the shift from an inactive to an active state. These results suggest that CR3-mediated binding and detachment of cells is not driven by a reversible change in affinity but by two mechanistically distinct processes, an energetically neutral activation step for binding and an energy-dependent step that reverses binding of ligand. PMID- 7782297 TI - Acetylcholine differentially affects intracellular calcium via nicotinic and muscarinic receptors on the same population of neurons. AB - Multiple receptor subtypes activated by the same ligand but coupled to different second messengers can produce divergent signaling in a cell, while receptors activated by different ligands but sharing the same second messenger can produce convergent signaling. We show here that chick ciliary ganglion neurons have three classes of receptors activated by the same neurotransmitter, acetylcholine, and that all three regulate the same second messenger, intracellular free calcium. Activation of muscarinic receptors on the neurons stimulates phosphatidylinositol turnover and induces calcium oscillations that are initiated and maintained by calcium release from caffeine/ryanodine-insensitive intracellular stores. Extracellular calcium is required to sustain the oscillations, while cadmium abolishes them. Activation of either of two classes of nicotinic receptors, distinguished both by location on the neurons and by subunit composition, induces a single, rapid elevation in intracellular calcium without inducing phosphatidylinositol turnover. The nicotinic responses are entirely dependent on extracellular calcium, show no dependence on release from internal stores, and do not display oscillations. Low concentrations of the native agonist, acetylcholine, induce repetitive calcium spikes in the neurons characteristic of muscarinic receptors, while higher concentrations induce nonoscillating increases in intracellular calcium that include contributions from nicotinic receptors. The three classes of receptors also differ in the acetylcholine concentration required to elicit a response. These differences, together with differences in receptor location and sources of calcium mobilized, may enable the receptor subtypes to target different sets of calcium-dependent processes for regulation. PMID- 7782298 TI - Regulation of vascular smooth muscle cell insulin-like growth factor I receptors by phosphorothioate oligonucleotides. Effects on cell growth and evidence that sense targeting at the ATG site increases receptor expression. AB - We have recently shown that insulin-like growth factor I (IGF I) is a mediator of angiotensin II-induced mitogenesis in vascular smooth muscle cells (Delafontaine, P., and Lou H. (1993) J. Biol. Chem. 268, 16866-16870). To study the role of the IGF I receptor in vascular smooth muscle cell growth, phosphorothioate oligonucleotides were used to modulate IGF I receptors. An antisense oligonucleotide targeting the ATG site inhibited basal and serum-induced DNA synthesis in vascular smooth muscle cells. Mismatch oligonucleotide had no effect, while surprisingly sense oligonucleotide increased IGF I receptor number and basal and serum-induced DNA synthesis. A 51% reduction in IGF I receptor number following exposure to 5 microM antisense oligonucleotide markedly inhibited angiotensin II-induced mitogenesis. A 70% increase in IGF I receptor number following exposure to 5 microM sense oligonucleotide resulted in a 4-fold increase in basal [3H]thymidine incorporation, and angiotensin II (1-1000 nM) had no additive stimulatory effect. An antisense oligonucleotide targeting a sequence starting at +109 base pairs (relative to ATG) also reduced IGF I receptor number, however, the corresponding sense oligonucleotide was without effect. These findings demonstrate that alterations in vascular smooth muscle cell IGF I receptor density play a critical role in the proliferative response of vascular smooth muscle cells to serum and to angiotensin II. In addition, the surprising observation that an ATG-directed sense oligonucleotide up-regulates IGF I receptors identifies a novel effect of oligonucleotides on gene expression. PMID- 7782299 TI - Phage T4 DNA [N6-adenine]methyltransferase. Overexpression, purification, and characterization. AB - The bacteriophage T4 dam gene, encoding the Dam DNA [N6-adenine]methyltransferase (MTase), has been subcloned into the plasmid expression vector, pJW2. In this construct, designated pINT4dam, transcription is from the regulatable phage lambda pR and pL promoters, arranged in tandem. A two-step purification scheme using DEAE-cellulose and phosphocellulose columns in series, followed by hydroxyapatite chromatography, was developed to purify the enzyme to near homogeneity. The yield of purified protein was 2 mg/g of cell paste. The MTase has an s20,w of 3.0 S and a Stokes radius of 23 A and exists in solution as a monomer. The Km for the methyl donor, S-adenosylmethionine, is 0.1 x 10(-6) M, and the Km for substrate nonglucosylated, unmethylated T4 gt- dam DNA is 1.1 x 10(-12) M. The products of DNA methylation, S-adenosyl-L-homocysteine and methylated DNA, are competitive inhibitors of the reaction; Ki values of 2.4 x 10(-6) M and 4.6 x 10(-12) M, respectively, were observed. T4 Dam methylates the palindromic tetranucleotide, GATC, designated the canonical sequence. However, at high MTase:DNA ratios, T4 Dam can methylate some noncanonical sequences belonging to GAY (where Y represents cytosine or thymine). PMID- 7782301 TI - Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. AB - Transport by discrete vesicular carriers is well established at least in part because of recent discoveries identifying key protein mediators of vesicle formation, docking, and fusion. A general mechanism sensitive to N-ethylmaleimide (NEM) is required for the transport of a divergent group of vesicular carriers in all eukaryotes. Many endothelia have an abundant population of non-coated plasmalemmal vesicles or caveolae, which have been reported with considerable controversy to function in transport. We recently have shown that like other vesicular transport systems, caveolae-mediated endocytosis and transcytosis are inhibited by NEM (Schnitzer, J. E., Allard, J., and Oh, P. (1995) Am. J. Physiol. 268, H48-H55). Here, we continue this work by utilizing our recently developed method for purifying endothelial caveolae from rat lung tissue (Schnitzer, J. E., Oh, P., Jacobson, B. S., and Dvorak, A. M. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 1759-1763) to show that these caveolae contain key proteins known to mediate different aspects of vesicle formation, docking, and/or fusion including the vSNARE VAMP-2, monomeric and trimeric GTPases, annexins II and VI, and the NEM sensitive fusion factor NSF along with its attachment protein SNAP. Like neuronal VAMPs, this endothelial VAMP is sensitive to cleavage by botulinum B and tetanus neurotoxins. Caveolae in endothelium are indeed like other carrier vesicles and contain similar NEM-sensitive molecular machinery for transport. PMID- 7782302 TI - The C terminus of the nuclear RAN/TC4 GTPase stabilizes the GDP-bound state and mediates interactions with RCC1, RAN-GAP, and HTF9A/RANBP1. AB - Ran/TC4 is a member of the Ras superfamily of GTPases. It is unusual in being predominantly nuclear and because it possesses an acidic -DEDDDL sequence instead of a consensus prenylation domain at the C terminus. Ran is required for nuclear protein import and cell cycle progression, and has been implicated in mRNA processing and export and DNA replication. The inhibition of cell cycle progression by a dominant gain-of-function mutant of Ran has been shown to be abrogated by removal of the -DEDDDL sequence, suggesting that this domain is essential for Ran function. We demonstrate here that the -DEDDDL sequence stabilizes GDP binding to Ran, and that the domain is required for high affinity interaction with a Ran-binding protein, HTF9A/RanBP1. HTF9A functions as a co stimulator of Ran-GAP (GTPase activating protein) activity on wild-type Ran, but in the absence of the acidic C terminus of Ran, HTF9A behaves as a Ran-GAP inhibitor. An antibody directed against the C-terminal region preferentially recognizes the GTP-bound form of Ran, suggesting that this domain undergoes a nucleotide-dependent conformational change. The results suggest that the acidic C terminal domain is important in modulating the interaction of Ran with regulatory factors, and implicate Ran-binding proteins in mediating the effects of Ran on cell cycle progression. PMID- 7782300 TI - Critical contributions of amino-terminal extracellular domains in agonist binding and activation of secretin and vasoactive intestinal polypeptide receptors. Studies of chimeric receptors. AB - Secretin and vasoactive intestinal polypeptide (VIP) receptors are closely related G protein-coupled receptors in a recently described family possessing a large amino-terminal ectodomain. We postulated that this domain might be critical for agonist recognition and therefore constructed a series of six chimeric receptors, exchanging the amino terminus, the first extracellular loop, or both in secretin and VIP receptors. Constructs were expressed in COS cells and characterized by cAMP generation and binding of both secretin and VIP radio ligands. Wild type receptors demonstrated high affinity binding of respective ligands (IC50 values (in nM): at the secretin receptor: 2.2 for secretin, > 1000 for VIP; at the VIP receptor: 2.2 for VIP, > 1000 for secretin) and appropriately sensitive and selective biological responses (EC50 values (in nM): at the secretin receptor: 1.5 for secretin, 127 for VIP; at the VIP receptor: 1.0 for VIP, 273 for secretin). Replacement of the secretin receptor amino terminus with that of the VIP receptor resulted in biological responsiveness typical of the VIP receptor (EC50 = 120 nM for secretin, 1.7 nM for VIP). The converse was not true, with this domain of the secretin receptor not able to provide the same response when incorporated into the VIP receptor (EC50 = 50 nM for VIP, 30 nM for secretin). The addition of both the first loop and the amino terminus of the secretin receptor was effective in yielding a secretin receptor-like response (EC50 = 2.0 nM for secretin, 47 nM for VIP). All chimeric constructs expressing selectivity for secretin-stimulated activity bound this hormone with high affinity (IC50 = 0.2-2.2 nM); however, there was divergence between VIP binding and biological activity. Thus, the amino terminus of secretin and VIP receptors plays a key role in agonist recognition and responsiveness, with the first loop playing a critical complementary role for the secretin receptor. PMID- 7782303 TI - Structural organization of procaryotic and eucaryotic Hsp90. Influence of divalent cations on structure and function. AB - Hsp90 is a very abundant molecular chaperone that apparently helps to protect cellular proteins from denaturation upon temperature upshift. The unusual ability of Hsp90 to function under conditions where other proteins unfold prompted us to investigate the stability and structural organization of Hsp90 itself. Both procaryotic and eucaryotic members of the Hsp90 family were found to have very similar physicochemical properties: (i) they are stable against thermal unfolding up to at least 50 degrees C, (ii) they show biphasic, reversible unfolding transitions in guanidinium chloride, and (iii) their oligomerization state is strongly and rapidly affected by millimolar concentrations of divalent cations. In the presence of MnCl2 and MgCl2 defined changes in the quaternary structure of Hsp90 could be observed which resulted in a decrease in thermostability and an increased tendency to form larger aggregates. The addition of divalent cations also almost completely abolished the chaperone function of Hsp90 and induced release of folding intermediates of citrate synthase bound to Hsp90. These modulating effects of divalent cations on structure and function of Hsp90 in vitro represent a potential mechanism for regulation of Hsp90 chaperone action in vivo. PMID- 7782304 TI - Molecular cloning of the isoquinoline 1-oxidoreductase genes from Pseudomonas diminuta 7, structural analysis of iorA and iorB, and sequence comparisons with other molybdenum-containing hydroxylases. AB - The iorA and iorB genes from the isoquinoline-degrading bacterium Pseudomonas diminuta 7, encoding the heterodimeric molybdo-iron-sulfur-protein isoquinoline 1 oxidoreductase, were cloned and sequenced. The deduced amino acid sequences IorA and IorB showed homologies (i) to the small (gamma) and large (alpha) subunits of complex molybdenum-containing hydroxylases (alpha beta gamma/alpha 2 beta 2 gamma 2) possessing a pterin molybdenum cofactor with a monooxo-monosulfido-type molybdenum center, (ii) to the N- and C-terminal regions of aldehyde oxidoreductase from Desulfovibrio gigas, and (iii) to the N- and C-terminal domains of eucaryotic xanthine dehydrogenases, respectively. The closest similarity to IorB was shown by aldehyde dehydrogenase (Adh) from the acetic acid bacterium Acetobacter polyoxogenes. Five conserved domains of IorB were identified by multiple sequence alignments. Whereas IorB and Adh showed an identical sequential arrangement of these conserved domains, in all other molybdenum-containing hydroxylases the relative position of "domain A" differed. IorA contained eight conserved cysteine residues. The amino acid pattern harboring the four cysteine residues proposed to ligate the Fe/S I cluster was homologous to the consensus binding site of bacterial and chloroplast-type [2Fe 2S] ferredoxins, whereas the pattern including the four cysteines assumed to ligate the Fe/S II center showed no similarities to any described [2Fe-2S] binding motif. The N-terminal region of IorB comprised a putative signal peptide similar to typical leader peptides, indicating that isoquinoline 1-oxidoreductase is associated with the cell membrane. PMID- 7782305 TI - A role for 3AB protein in poliovirus genome replication. AB - The poliovirus polypeptide 3AB, the precursor of the genome-bound VPg protein, stimulates in vitro the synthesis of poly(U) directed by the viral polymerase 3Dpol (Lama, J., Paul, A., Harris, K., and Wimmer, E. (1994) J. Biol. Chem. 269, 66-70), suggesting that 3AB could be modulating the activity of the viral polymerase in poliovirus-infected cells. To address the exact function of 3AB in the viral replication cycle, a biochemical and molecular genetic analysis of 3AB has been carried out. 3AB protein bound RNA probes in two different assays, and amino acid positions implicated in the RNA binding activity of 3AB were determined. Mutant proteins with reduced RNA binding activity were unable to stimulate 3Dpol polymerase activity. Purified protein 3A showed no RNA binding or 3Dpol stimulatory activity, but 3A and VPg mutations conferred a synergistic effect on the 3AB functions. Polioviruses encoding for these mutant 3ABs were constructed. These mutant viruses translated their RNA genomes in vitro and processed their polyproteins as wild type virus did. Cells infected with 3AB mutant viruses showed over 90% inhibition in the accumulation of plus and minus viral RNA strands and more than 100-fold reduction of virus yield at 4 h postinfection. Our results suggest that 3AB protein functions in vivo as a co factor of the viral polymerase and that the activity of 3AB may be regulated by proteolytic processing. PMID- 7782306 TI - Comparison of the enzymatic properties of the two Escherichia coli lysyl-tRNA synthetase species. AB - In Escherichia coli, lysyl-tRNA synthetase activity is encoded by either a constitutive lysS gene or an inducible one, lysU. The two corresponding enzymes could be purified at homogeneity from a delta lysU and a delta lysS strain, respectively. Comparison of the pure enzymes, LysS and LysU, indicates that, in the presence of saturating substrates, LysS is about twice more active than LysU in the ATP-PPi exchange as well as in the tRNALys aminoacylation reaction. Moreover, the dissociation constant of the LysU-lysine complex is 8-fold smaller than that of the LysS-lysine complex. In agreement with this difference, the activity of LysU is less sensitive than that of LysS to the addition of cadaverine, a decarboxylation product of lysine and a competitive inhibitor of lysine binding to its synthetase. This observation points to a possible useful role of LysU, under physiological conditions causing cadaverine accumulation in the bacterium. Remarkably, these conditions also induce lysU expression. Homogeneous LysU and LysS were also compared in Ap4A synthesis. LysU is only 2 fold more active than LysS in the production of this dinucleotide. This makes unlikely that the heat-inducible LysU species could be preferentially involved in the accumulation of Ap4A inside stressed Escherichia coli cells. This conclusion could be strengthened by determining the concentrations of Ap4N (N = A, C, G, or U) in a delta lysU as well as in a lysU+ strain, before and after a 1-h temperature shift at 48 degrees C. The measured concentration values were the same in both strains. PMID- 7782307 TI - Gluconeogenesis and intrahepatic triose phosphate flux in response to fasting or substrate loads. Application of the mass isotopomer distribution analysis technique with testing of assumptions and potential problems. AB - We measured gluconeogenesis (GNG) in rats by mass isotopomer distribution analysis, which allows enrichment of the true biosynthetic precursor pool (hepatic cytosolic triose phosphates) to be determined. Fractional GNG from infused [3-13C]lactate, [1-13C]lactate, and [2-13C]glycerol was 88 +/- 2, 89 +/- 3, and 87 +/- 2%, respectively, after 48 h of fasting. [2-13C]Glycerol was the most efficient label and allowed measurement of rate of appearance of intrahepatic triose phosphate (Ra triose-P), by dilution. IV fructose (10-15 mg/kg/min) increased absolute GNG by 81-147%. Ra triose-P increased proportionately, but endogenous Ra triose-P was almost completely suppressed, suggesting feedback control. Interestingly, 15-17% of fructose was directly converted to glucose without entering hepatic triose-P. IV glucose reduced GNG and Ra triose-P. 24-h fasting reduced hepatic glucose production by half, but absolute GNG was unchanged due to increased fractional GNG (51-87%). Reduced hepatic glucose production was entirely due to decreased glycogen input, from 7.3 +/- 1.8 to 1.1 +/- 0.2 mg/kg/min. Ra triose-P fell during fasting, but efficiency of triose-P disposal into GNG increased, maintaining GNG constant. Secreted glucuronyl conjugates and plasma glucose results correlated closely. In summary, GNG and intrahepatic triose-P flux can be measured by mass isotopomer distribution analysis with [2-13C]glycerol. PMID- 7782308 TI - Phosphatidylinositol 4-phosphate increases the rate of dephosphorylation of the phosphorylated Ca(2+)-ATPase. AB - Incubation of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum with ATP in the absence of Ca2+ leads to phosphorylation of phosphatidylinositol (PtdIns) to phosphatidylinositol 4-phosphate (PtdIns-4P) and to a doubling of ATPase activity. Similarly, reconstitution of the ATPase with mixtures of dioleoylphosphatidylcholine and PtdIns-4P also led to a doubling of activity; ATPase activity increased with increasing PtdIns-4P content, up to 10% beyond which no further increase was observed. Reconstitution with PtdIns had a much smaller effect on activity. Changes in the Ca2+ affinity of the ATPase following incubation with ATP or reconstitution with PtdIns-4P were small. The rates of phosphorylation of the ATPase by ATP and of the Ca2+ transport step were unaffected, but the rate of dephosphorylation of the phosphorylated ATPase increased by a factor of 2 either following incubation with ATP or following reconstitution with PtdIns-4P. Activation of the ATPase led to a decrease in the level of phosphorylation of the ATPase by Pi corresponding to a 10-fold decrease in the equilibrium constant E2PMg/E2PiMg. PMID- 7782309 TI - Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. AB - Previous studies demonstrated that tissue plasminogen activator-induced fibrinolysis in vitro is retarded in the presence of prothrombin (II) activation and that the anticoagulant-activated protein C appears profibrinolytic by preventing the formation of thrombin (IIa)-like activity during fibrinolysis. To disclose the molecular connection between the generation of IIa and the inhibition of fibrinolysis, a lysis assay that is sensitive to the antifibrinolytic effect of II activation was developed and was used to purify a 60-kDa single-chain protein from human plasma. Because the lysis of a clot, produced from purified components, is retarded when this protein is present and when II activation occurs in situ, the protein was named TAFI (thrombin activatable fibrinolysis inhibitor). TAFI is cleaved by IIa yielding 35-, 25-, and 14-kDa products. Amino-terminal sequence analyses identified TAFI as a precursor of a plasma carboxypeptidase B (CPB). Formation of the 35-kDa product correlates with both prolongation of lysis time and CPB-like activity. Prolongation of lysis time saturates at about 125 nM TAFI. Activated TAFI inhibits the activation of Glu-plasminogen but does not prolong the lysis of clots formed in the presence of Lys-plasminogen. 2-Guanidinoethylmercaptosuccinic acid, a competitive inhibitor of CPB, completely inhibits prolongation of lysis by activated TAFI in a purified system and the prolongation induced by II activation in barium-adsorbed plasma. This suggests that TAFI accounts for the antifibrinolytic effect that accompanies prothrombin activation and that activated protein C appears profibrinolytic by attenuating TAFI activation. PMID- 7782311 TI - A novel type of limulus lectin-L6. Purification, primary structure, and antibacterial activity. AB - Lipopolysaccharide (LPS)-binding protein(s) was first screened in the detergent extract of horseshoe crab (limulus) hemocytes using LPS-immobilized agarose. A protein, designated L6 (M(r) = 27,000), was found to bind to LPS-agarose and was eluted with EDTA or o-phenanthroline. The L6 protein, however, did not inhibit the LPS-mediated activation of a limulus serine protease zymogen factor C. L6 had an affinity to the matrix of Sepharose CL-6B itself, and it could be eluted with high concentrations of monosaccharides (0.5-1.0 M), such as glucose, mannose, and galactose, suggesting a lectin-like nature. The entire amino acid sequence of L6 was determined by sequencing peptides derived from CNBr and enzymatic cleavages. L6 contained 7 half-cystines, and 1 cysteine residue at position 201 had a free SH-group. In addition, positions of the remaining three intrachain disulfide bonds were assigned by amino acid and sequence analyses of three cystinyl peptides produced by lysyl endopeptidase digestion. These results indicated that the entire sequence of L6 consisted of 221 residues with no N-linked sugar and was composed of six tandem repeats, each consisting of 33-38 amino acid residues. Inductively coupled plasma spectrometry of L6 indicated the presence of 0.75 mol zinc/mol of protein. No significant sequence homology was observed between L6 and other proteins, including various animal lectins and LPS-binding proteins. However, L6 showed agglutinating activity on LPS-coated sheep erythrocytes and Gram-negative and Gram-positive bacteria, it inhibited the growth of Gram negative bacteria, and thus it presumably recognizes carbohydrate components in the cell wall of bacteria. PMID- 7782310 TI - Pleckstrin inhibits phosphoinositide hydrolysis initiated by G-protein-coupled and growth factor receptors. A role for pleckstrin's PH domains. AB - Pleckstrin is a 40-kDa protein present in platelets and leukocytes that contains two PH domains separated by a 150-residue intervening sequence. Pleckstrin is a major substrate for protein kinase C, but its function is unknown. The present studies examine the effects of pleckstrin on second messenger generation. When expressed in cos-1 or HEK-293 cells, pleckstrin inhibited 1) the G alpha-mediated activation of phospholipase C beta initiated by thrombin, M1-muscarinic acetylcholine, and angiotensin II receptors, 2) the stimulation of phospholipase C beta by constitutively active Gq alpha, 3) the G beta gamma-mediated activation of phospholipase C beta caused by alpha 2A-adrenergic receptors, and 4) the tyrosine phosphorylation-mediated activation of phospholipase C gamma caused by Trk A. However, pleckstrin had no effect on either the stimulation or inhibition of adenylyl cyclase. The inhibition of phosphoinositide hydrolysis caused by pleckstrin was similar in magnitude to that caused by activating protein kinase C with phorbol 12-myristate 13-acetate (PMA). When combined, pleckstrin and PMA had an additive effect, inhibiting phosphoinositide hydrolysis by as much as 90%. Structure-function analysis highlighted the role of pleckstrin's N-terminal PH domain in these events. Although deleting the C-terminal PH domain had no effect, deleting the N-terminal PH domain abolished activity (but not expression) and mutating a highly conserved tryptophan residue within the N-terminal PH domain decreased activity by one-third. Notably, however, a pleckstrin variant in which the N-terminal PH domain was replaced with a second copy of the C-terminal PH domain was nearly as active as native pleckstrin. These results show that: 1) pleckstrin can inhibit pathways leading to both phospholipase C beta- and phospholipase C gamma-mediated phosphoinositide hydrolysis, 2) this inhibition affects activation of phospholipase C beta mediated by either G alpha or G beta gamma, but does not affect the regulation of adenylyl cyclase activity by G alpha or G beta gamma, 3) although pleckstrin is a substrate for protein kinase C, the effects of pleckstrin and PMA are at least partially independent, 4) the inhibition caused by pleckstrin appears to be mediated by the PH domain at the N terminus, rather than the C terminus of the molecule, and 5) location of the two PH domains within the molecule clearly contributes to their individual activity.2+1 PMID- 7782313 TI - Sequence and structural determinants of the interaction between the 5'-noncoding region of picornavirus RNA and rhinovirus protease 3C. AB - It has previously been established that human rhinovirus 14 protease 3C binds specifically to the 5'-noncoding region of the viral RNA. A series of mutants of protease 3C and deletion or point mutants of the 5'-noncoding region of the viral RNA were analyzed to elucidate the sites of interaction between the protease and the RNA. Amino acids in protease 3C essential for RNA binding were found to be discontinuous in the amino acid sequence, and mutations which destroyed RNA binding did not affect the catalytic (proteolytic) activity of protease 3C. Based on the three-dimensional structure of rhinovirus 14 protease 3C, the RNA binding region is located in an extended area distinct from the catalytic triad. A single stem-loop structure of 27 nucleotides (stem-loop d) in the 5'-noncoding region was necessary and sufficient to bind protease 3C. Mutagenesis of either the base paired stem or unpaired loop or bulge regions of stem-loop d suggested that the base-paired stem, but not the loop or bulge, carries important determinants of protease 3C binding. This conclusion is strengthened by the observation that rhinovirus 14 protease 3C bound specifically to the 5'-noncoding region of poliovirus RNA, and only the base-paired stem of stem-loop d is conserved between poliovirus and rhinovirus RNAs. PMID- 7782312 TI - Erythropoietin-dependent inhibition of apoptosis is supported by carboxyl truncated receptor forms and blocked by dominant-negative forms of Jak2. AB - Apoptosis, or programmed cell death (PCD), recently has emerged as an important homeostatic mechanism within several hematopoietic lineages. This process is subject to both positive and negative modulation by cytokines and within the erythroid lineage is inhibited by interleukin-3, stem cell factor, and erythropoietin (Epo). Through the expression of carboxyl-truncated Epo receptor mutants in FDC-P1 cells, a receptor form possessing 80 membrane-proximal cytoplasmic residues is shown to efficiently mediate Epo-dependent inhibition of PCD. This is in contrast to previous studies that attributed this activity to a distal carboxyl-terminal receptor subdomain (and/or heterodimerization of wild type Epo receptors with a truncated non-functional receptor form). Epo-dependent inhibition of PCD also is shown to be blocked by ectopic expression of kinase deficient dominant-negative forms of Jak2 (Jak2 delta VIII and Jak2-829), further underlining a role of this membrane-proximal subdomain of the Epo receptor in the inhibition of PCD. To our knowledge, this comprises the first direct evidence for an essential role for a Jak tyrosine kinase (Jak2) in this apoptotic response pathway. PMID- 7782315 TI - Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons. AB - The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal beta-type EGF-like domain and an unique N terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185erbB2, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system. PMID- 7782314 TI - Gamma chain-associated cytokine receptors signal through distinct transducing factors. AB - The IL-2, IL-4, and IL-7 signaling pathways have been shown to utilize shared components. The receptors for these cytokines are composed of ligand-specific binding chains that associate with a shared signaling subunit, the common gamma (gamma c) chain. In addition, IL-2, IL-4, and IL-7 induce activation of a common set of nonreceptor tyrosine kinases, Jak-1 and Jak-3. We have further investigated the signaling events induced by these cytokines and find that the gamma c-associated receptors activate distinct signal transducing factors (STFs). In addition, we show that a 94-kDa STAT-related protein (p94) is activated in response to IL-2 and IL-7, but not IL-4. These data indicate that IL-2, IL-4, and IL-7 activate distinct signaling molecules which might be differentially recruited to the receptor complex by the ligand-specific units of the IL-2, IL-4, and IL-7 receptors. PMID- 7782316 TI - Neuronal cell expression of inserted isoforms of vertebrate nonmuscle myosin heavy chain II-B. AB - Previous work has demonstrated that unique isoforms of nonmuscle myosin heavy chain II-B (MHC-B) are expressed in chicken and human neuronal cells (Takahashi, M., Kawamoto, S., and Adelstein, R. S. (1992) J. Biol. Chem. 267, 17864-17871). These isoforms, which appear to be generated by alternative splicing of pre-mRNA, differ from the MHC-B isoform present in a large number of nonmuscle cells in that they contain inserted cassettes of amino acids near the ATP binding region and/or near the actin binding region. The insert near the ATP binding region begins after amino acid 211 and consists of either 10 or 16 amino acids. The insert near the actin binding region begins after amino acid 621 and consists of 21 amino acids. Using a variety of techniques, we have studied the distribution and expression of the inserted MHC-B isoforms. In the developing chicken brain, mRNA encoding the 10-amino acid insert gradually increases after embryonic day 4, peaks in the 10-14-day embryo, and then declines. In contrast, the mRNA encoding the 21-amino acid insert appears just before birth and is abundantly expressed in the adult chicken cerebellum. There is a marked species difference between the distribution of the inserted isoforms in adult tissues. The mRNA encoding MHC-B containing the 10-amino acid insert near the ATP binding region is expressed at low levels in the adult chicken brain, but makes up most of the MHC-B mRNA expressed in the human cerebrum and approximately 90% of MHC-B in the human retina. It is also expressed in neuronal cell lines. The mRNA encoding MHC-B containing the 21-amino acid insert is abundantly expressed in the chicken cerebellum and human cerebrum, but is absent from the retina and cell lines. Employing human retinoblastoma (Y-79) and neuroblastoma (SK-N-SH) cell lines, an increase in expression of mRNA encoding the 10-amino acid inserted isoform was seen following treatment by a number of agonists or by serum deprivation. In each case, expression of the inserted MHC-B isoform correlated with cell differentiation (neuronal phenotype) and inhibition of cell division. Using a rat pheochromocytoma cell line (PC12), we found that prior to treatment with nerve growth factor (NGF), there was no evidence for either inserted isoform, although noninserted MHC-B was present. NGF treatment resulted in the appearance of mRNA encoding MHC-B containing the 10-amino acid insert, concomitant with neurite outgrowth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782318 TI - Identification of lysines within alpha 1-antichymotrypsin important for DNA binding. An unusual combination of DNA-binding elements. AB - The human serum serine protease inhibitor (serpin) alpha 1-antichymotrypsin (ACT) appears to be unique among serpins in its ability to bind to double-stranded DNA. Using site-directed mutagenesis and chemical modification, a tri-lysine sequence (residues 210-212) falling within a solvent exposed loop and the C-terminal peptide containing two lysines (residues 391 and 396) were shown to be important for DNA binding. Mutation of residues 210-212 from lysines to either glutamates or threonines abolished DNA binding. The Lys210-Thr211-212 and Thr210-Th4(211) Lys212 variants displayed reduced affinity for DNA, especially at higher ionic strength. Limited acetylation of rACT with acetic anhydride led to loss of DNA binding and, conversely, DNA protected rACT from acetylation. A combination of CNBr digestion, peptide separation, and peptide sequencing identified Lys396, two residues from the C terminus, as the most reactive lysine in rACT. Acetylation of Lys396 is strongly decreased in the presence of DNA. The double mutant K391T/K396T-rACT had very little affinity for DNA. The epsilon-amines of lysines 210-212 are 8-15 A across a cleft from the epsilon-amines in Lys391 and Lys396, and together these two elements may form an unusual DNA binding domain. Attempts to isolate a DNA sequence to which ACT binds specifically have been unsuccessful to date, raising the possibility that nonspecific binding of ACT to DNA suffices to account for the ACT found in certain cell nuclei. ACT variants not binding to double-stranded DNA retain ACT protease inhibitory activity, a potentially important result for the use of ACT variants as therapeutic agents. PMID- 7782317 TI - Phosphorylation of elongation factor Tu prevents ternary complex formation. AB - The elongation factor Tu (EF-Tu) is a member of the GTP/GDP-binding proteins and interacts with various partners during the elongation cycle of protein biosynthesis thereby mediating the correct binding of amino-acylated transfer RNA (aa-tRNA) to the acceptor site (A-site) of the ribosome. After GTP hydrolysis EF Tu is released in its GDP-bound state. In vivo, EF-Tu is post-translationally modified by phosphorylation. Here we report that the phosphorylation of EF-Tu by a ribosome associated kinase activity is drastically enhanced by EF-Ts. The antibiotic kirromycin, known to block EF-Tu function, inhibits the modification. This effect is specific, since kirromycin-resistant mutants do become phosphorylated in the presence of the antibiotic. On the other hand, phosphorylated wild-type EF-Tu does not bind kirromycin. Most interestingly, the phosphorylation of EF-Tu abolishes its ability to bind aa-tRNA. In the GTP conformation the site of modification is located at the interface between domains 1 and 3 and is involved in a strong interdomain hydrogen bond. Introduction of a charged phosphate group at this position will change the interaction between the domains, leading to an opening of the molecule reminiscent of the GDP conformation. A model for the function of EF-Tu phosphorylation in protein biosynthesis is presented. PMID- 7782319 TI - Subsite affinities and disposition of catalytic amino acids in the substrate binding region of barley 1,3-beta-glucanases. Implications in plant-pathogen interactions. AB - Oligo-1,3-beta-glucosides with degrees of polymerization of 2-9 were labeled at their reducing terminal residues by catalytic tritiation. These substrates were used in detailed kinetic and thermodynamic analyses to examine substrate binding in 1,3-beta-D-glucan glucanohydrolase (EC 3.2.1.39) isoenzymes GI, GII, and GIII from young seedlings of barley (Hordeum vulgare). Bond-cleavage frequencies, together with the kinetic parameter kcat/Km, have been calculated as a function of substrate chain length to define the number of subsites that accommodate individual beta-glucosyl residues and to estimate binding energies at each subsite. Each isoenzyme has eight beta-glucosyl-binding subsites. The catalytic amino acids are located between the third and fourth subsite from the nonreducing terminus of the substrate. Negative binding energies in subsites adjacent to the hydrolyzed glycosidic linkage suggest that some substrate distortion may occur in this region during binding and that the resultant strain induced in the substrate might facilitate hydrolytic cleavage. If the 1,3-beta-glucanases exert their function as pathogenesis-related proteins by hydrolyzing the branched or substituted 1,3;1,6-beta-glucans of fungal walls, it is clear that relatively extended regions of the cell wall polysaccharide must fit into the substrate binding cleft of the enzyme. PMID- 7782320 TI - Human macrophage metalloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression. AB - Human macrophage metalloelastase (HME) is a recent addition to the matrix metalloproteinase (MMP) family that was initially found to be expressed in alveolar macrophages of cigarette smokers. To understand more about HME expression, analysis of the structure and location of the gene was performed. The gene for HME is composed of 10 exons and 9 introns, similar to the stromelysins and collagenases, and HME shares the highly conserved exon size and intron-exon borders with other MMPs. The 13-kilobase (kb) HME gene has been localized by fluorescence in situ hybridization to chromosome 11q22.2-22.3, the same location of the interstitial collagenase and stromelysin genes. We determined that HME and stromelysin 1 genes are physically linked within 62 kb utilizing pulse-field gel electrophoresis. The promoter region of the HME gene contains several features common to other MMP genes including a TATA box 29 bp upstream to the transcription initiation site, an AP-1 motif, and a PEA3 element. HME mRNA is not detectable in normal adult tissues but is induced in rapidly remodeling tissues such as the term placenta. In situ hybridization and immunohistochemistry of placental tissue demonstrated HME mRNA and protein expression in macrophages and stromal cells. Cell-specific expression and response to inflammatory stimuli such as endotoxin is conferred within 2.8 kb of the HME 5'-flanking sequence as demonstrated by HME promoter-CAT expression constructs. Knowledge of the genomic organization and chromosomal location of HME may allow us to further define mechanisms responsible for cell- and tissue-specific expression of HME. PMID- 7782321 TI - Purification of mu-calpain by a novel affinity chromatography approach. New insights into the mechanism of the interaction of the protease with targets. AB - A calmodulin-binding motif is a common structural feature of a number of calpain substrates (1). Since a calmodulin-like domain has been identified in both subunits of the calpain molecule, the proposal was made that the domain(s) would recognize the calmodulin-binding motifs of the substrates prior to the enzymatic modification by calpain. In keeping with the proposal, a successful attempt to purify mu-calpain from human erythrocytes was made by using an affinity chromatography approach in which the synthetic peptide C49, containing the calmodulin-binding domain of the plasma membrane Ca(2+)-ATPase, was coupled to a Sepharose matrix. The calmodulin-like domain of the catalytic subunit of human mu calpain expressed in Escherichia coli was also retained by the C49-Sepharose column. Both mu-calpain and the calmodulin-like domain interacted with C49 in a Ca(2+)-dependent way and were eluted from the column by Ca(2+)-chelating agents. The finding confirmed the interaction between the calmodulin-binding domain of the plasma membrane Ca(2+)-ATPase and the calmodulin-like domain of mu-calpain. Experiments were performed to establish whether irreversibly inactivated mu calpain or its expressed C-terminal portion containing the calmodulin-like domain could activate the hydrolysis of ATP by the plasma membrane Ca2+ pump, in keeping with evident ATPase stimulation of the same pump by calmodulin. A stimulation was observed, but it was much weaker than that induced by calmodulin. PMID- 7782323 TI - Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. AB - Initiation factor 4E (eIF-4E) binds to the m7GTP-containing cap of eukaryotic mRNA and facilitates the entry of mRNA into the initiation cycle of protein synthesis. eIF-4E is a phosphoprotein, and the phosphorylated form binds to mRNA caps 3-4-fold more tightly than the nonphosphorylated form. A previous study indicated that the major phosphorylation site was Ser-53 (Rychlik, W., Russ, M. A., and Rhoads, R. E. (1987) J. Biol. Chem. 262, 10434-10437). In the present study, we synthesized the phosphopeptide expected to result from tryptic digestion of eIF-4E, O-phosphoseryllysine. Surprisingly, the tryptic and synthetic phosphopeptides did not comigrate electrophoretically. Accordingly, we redetermined the phosphorylation site by isolating a chymotryptic phosphopeptide on reverse phase high performance liquid chromatography. The peptide was sequenced by Edman degradation and corresponded to 198QSHADTATKSGSTTKNRF215. The site of phosphorylation was determined to be Ser-209 by four methods: the increase in the ratio of dehydroalanine to serine derivatives during Edman degradation, the release of 32P, the further digestion of the chymotryptic phosphopeptide with trypsin, Glu-C, and Asp-N, and site-directed mutagenesis of eIF-4E cDNA. The S209A variant was not phosphorylated in a rabbit reticulocyte lysate system, whereas the wild-type, S53A, and S207A variants were. This site falls within the consensus sequence for phosphorylation by protein kinase C. PMID- 7782324 TI - Regulation of RCK1 currents with a cAMP analog via enhanced protein synthesis and direct channel phosphorylation. AB - We have recently shown that the rat brain Kv1.1 (RCK1) voltage-gated K+ channel is partially phosphorylated in its basal state in Xenopus oocytes and can be further phosphorylated upon treatment for a short time with a cAMP analog (Ivanina, T., Perts, T., Thornhill, W. B., Levin, G., Dascal, N., and Lotan, I. (1994) Biochemistry 33, 8786-8792). In this study, we show, by two-electrode voltage clamp analysis, that whereas treatments for a short time with various cAMP analogs do not affect the channel function, prolonged treatment with 8 bromoadenosine 3',5'-cyclic monophosphorothioate ((Sp)-8-Br-cAMPS), a membrane permeant cAMP analog, enhances the current amplitude. It also enhances the current amplitude through a mutant channel that cannot be phosphorylated by protein kinase A activation. The enhancement is inhibited in the presence of (Rp) 8-Br-cAMPS, a membrane-permeant protein kinase A inhibitor. Concomitant SDS polyacrylamide gel electrophoresis analysis reveals that this treatment not only brings about phosphorylation of the wild-type channel, but also increases the amounts of both wild-type and mutant channel proteins; the latter effect can be inhibited by cycloheximide, a protein synthesis inhibitor. In the presence of cycloheximide, the (Sp)-8-Br-cAMPS treatment enhances only the wild-type current amplitudes and induces accumulation of wild-type channels in the plasma membrane of the oocyte. In summary, prolonged treatment with (Sp)-8-Br-cAMPS regulates RCK1 function via two pathways, a pathway leading to enhanced channel synthesis and a pathway involving channel phosphorylation that directs channels to the plasma membrane. PMID- 7782322 TI - A novel mitogen-activated protein kinase phosphatase. Structure, expression, and regulation. AB - Mitogen-activated protein (MAP) kinase lies at the convergence of various extracellular ligand-mediated signaling pathways. It is activated by the dual specificity kinase, MAP kinase kinase or MEK. MAP kinase inactivation is mediated by dephosphorylation via specific MAP kinase phosphatases (MKPs). One MKP (MKP-1 (also known as 3CH134, Erp, or CL100)) has been reported to be expressed in a wide range of tissues and cells. We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells. MKP-2 showed significant homology with MKP-1 (58.8% at the amino acid level) and, like MKP-1, displayed vanadate-sensitive phosphatase activity against MAP kinase in vitro. Overexpression of MKP-2 in vivo inhibited MAP kinase-dependent gene transcription in PC12 cells. MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions. PMID- 7782326 TI - Molecular cloning of Sia alpha 2,3Gal beta 1,4GlcNAc alpha 2,8-sialyltransferase from mouse brain. AB - A cDNA encoding a new alpha 2,8-sialyltransferase (ST8Sia III), which exhibits activity toward the Sia alpha 2,3Gal beta 1, 4GlcNAc sequences of N-linked oligosaccharides, was cloned from mouse brain by means of the polymerase chain reaction-based approach. The predicted amino acid sequence of ST8Sia III showed 27.6 and 34.4% identity with those of so far cloned mouse alpha 2,8 sialyltransferases, i.e. GD3 synthase (ST8Sia I) and STX (ST8Sia II), respectively. Transfection of the protein A-fused ST8Sia III gene into COS-7 cells led to alpha 2,8-sialyltransferase activity toward sialylated glycoproteins and alpha 2,3-sialylated glycosphingolipids, such as alpha 2,3 sialylparagloboside and GM3. However, the kinetic properties of ST8Sia III revealed that it is much more specific to N-linked oligosaccharides of glycoproteins than glycosphingolipids. The expression pattern of the ST8Sia III gene was clearly different from those of other alpha 2,8-sialyltransferase genes. The expression of the ST8Sia III gene was tissue and stage specific. The ST8Sia III gene was expressed only in brain and testis, and it appeared first in 20 postcoitum embryonal brain and then decreased. Therefore, the new alpha 2,8 sialyltransferase is closely involved in brain development. PMID- 7782325 TI - Identification of three proteins in the eye of Aplysia, whose synthesis is altered by serotonin (5-HT). Possible involvement of these proteins in the ocular circadian system. AB - Previous results using translation inhibitors in the ocular circadian system of Aplysia suggest that protein synthesis may be involved in the light and serotonin (5-HT) entrainment pathways or perhaps in the circadian oscillator. Proteins have been previously identified whose synthesis was altered by treatments of light capable of perturbing the phase of the circadian rhythm in the eye of Aplysia. We extended these studies by investigating the effects of other treatments that perturb the ocular circadian rhythm on protein synthesis. 5-HT altered the synthesis of nine proteins. Interestingly, five of the proteins affected by treatments with 5-HT were previously shown to be affected by treatments with light. Four of the proteins affected by treatments with 5-HT were also affected by treatments with analogs of cAMP, a treatment which mimics the effects of 5-HT on the ocular circadian rhythm. To identify the cellular function of some of these proteins, we obtained their partial amino acid sequences. Based on these sequences and additional characterizations, a 78-kDa, pI 5.6 Aplysia protein appears to be glucose-regulated protein 78/binding protein, and a 36-kDa, pI 5.7 Aplysia protein appears to be porin/voltage-dependent anion channel. Heat shock experiments on Aplysia eyes revealed that yet another one of the Aplysia proteins (70 kDa) affected by 5-HT appears to be a heat-inducible member (heat shock protein 70) of the family of heat shock proteins. These findings suggest that these three identified proteins, together or individually, may be involved in some way in the regulation of the timing of the circadian oscillator in the eye of Aplysia. PMID- 7782327 TI - Isolation and characterization of a stable Chinese hamster ovary cell line overexpressing the plasma membrane Ca(2+)-ATPase. AB - Stable Chinese hamster ovary (CHO) cell lines overexpressing the human plasma membrane Ca(2+)-ATPase (PMCA) were generated, and three independent cell clones were characterized in details. They overexpressed high amounts of active PMCA pump (15-20 times over the amount of endogenous PMCA) as indicated by experiments in which the formation of the phosphoenzyme intermediate and the uptake of Ca2+ by microsomes were measured. Immunocytochemistry experiments coupled to the biotinylation of the pump in the intact cells indicated the correct deliver of the expressed pump to the plasma membrane. The expressed pump was purified by affinity chromatography on calmodulin sepharose. The PMCA of transfected CHO cells promoted an increase of Ca2+ into the medium, after induction of Ca2+ release from the internal stores by activation of a purinergic receptor. An evident decrease of the activity of the endogenous sarcoplasmic reticulum Ca(2+) ATPase pump was observed, probably related to the down-regulation of its expression. The cells overexpressing the PMCA pump had delayed recovery after trypsinization and plating. Their doubling time was, however, the same as CHO cells. PMID- 7782328 TI - Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria. AB - We examined the intracellular distribution of 8-oxo-dGTPase (8-oxo-7,8 dihydrodeoxyguanosine triphosphatase) encoded by the MTH1 gene, a human mutator homologue. The activity of 8-oxo-dGTPase mainly located in cytosolic and mitochondrial soluble fractions of Jurkat cells, a human T-cell leukemia line. Electron microscopic immunocytochemistry, using a specific antibody against MTH1 protein, showed localization of MTH1 protein in the mitochondrial matrix. Activity in the mitochondria accounted for about 4% of the total activity. The specific activity in the mitochondrial soluble fraction (8093 units/mg protein) was as high as that in the cytosolic fraction (8111 unit/mg protein). The 8-oxo dGTPase activities in cytosolic and mitochondrial soluble fractions co-eluted with MTH1 protein by anion-exchange chromatography, and the molecular mass of the mitochondrial MTH1 protein was much the same as that of the cytosolic MTH1 protein (about 18 kDa). HeLa cells expressing MTH1 cDNA showed an increased cytoplasmic signal together with a weak signal in the nucleus in in situ immunostaining of MTH1 protein, and the overexpressed MTH1 protein was recovered from both cytosolic and mitochondrial fractions. Thus, the 8-oxo-dGTPase encoded by MTH1 gene is localized in mitochondrial and cytosol. PMID- 7782329 TI - elt-2, a second GATA factor from the nematode Caenorhabditis elegans. AB - We have previously shown that a tandem pair of (A/T)GATA(A/G) sequences in the promoter region of the Caenorhabditis elegans gut esterase gene (ges-1) controls the tissue specificity of ges-1 expression in vivo. The ges-1 GATA region was used as a probe to screen a C. elegans cDNA expression library, and a gene for a new C. elegans GATA-factor (named elt-2) was isolated. The longest open reading frame in the elt-2 cDNA codes for a protein of M(r) 47,000 with a single zinc finger domain, similar (approximately 75% amino acid identity) to the C-terminal fingers of all other two-fingered GATA factors isolated to date. A similar degree of relatedness is found with the single-finger DNA binding domains of GATA factors identified in invertebrates. An upstream region in the ELT-2 protein with the sequence C-X2-C-X16-C-X2-C has some of the characteristics of a zinc finger domain but is highly diverged from the zinc finger domains of other GATA factors. The elt-2 gene is expressed as an SL1 trans-spliced message, which can be detected at all stages of development except oocytes; however, elt-2 message levels are 5-10-fold higher in embryos than in other stages. The genomic clone for elt-2 has been characterized and mapped near the center of the C. elegans X chromosome, ELT-2 protein, produced by in vitro transcription-translation, binds to ges-1 GATA-containing oligonucleotides similar to a factor previously identified in C. elegans embryo extracts, both as assayed by electrophoretic migration and by competition with wild type and mutant oligonucleotides. However, there is as yet no direct evidence that elt-2 does or does not control ges-1. PMID- 7782330 TI - Coupling of human D-1 dopamine receptors to different guanine nucleotide binding proteins. Evidence that D-1 dopamine receptors can couple to both Gs and G(o). AB - Coupling between D-1 dopamine receptors and G proteins in cell lines expressing human D-1 receptors and different G proteins was examined. Pertussis toxin (PTX) treatment of rat pituitary GH4C1 cells significantly reduced, but did not abolish, agonist high affinity binding sites of the D-1 dopamine receptor; in SK N-MC neuroblastoma cells, PTX failed to have any effect on D-1 high affinity sites. Cholera toxin (CTX) treatment of GH4C1 cells reduced but did not abolish the high affinity sites of D-1 receptors, while in SK-N-MC cells, treatment with CTX abolished all the high affinity sites. Western blot analyses with specific antisera indicated that Gs alpha, Gi1 alpha, Gi3 alpha, and Gq alpha were expressed in both cell lines, while Gi2 alpha and G(o) alpha were expressed in GH4C1 but not SK-N-MC cells. Antisera NEI-805 (anti-Gs alpha) and 9072 (anti-G(o) alpha) immunoprecipitated 24 +/- 4.3 and 34.4 +/- 6.9%, respectively, of G protein-associated D-1 dopamine receptors. Antisera 3646 (anti-Gi1 alpha), 1521 (anti-Gi2 alpha), 1518 (anti-Gi3 alpha), and 0941 (anti-Gq alpha) failed to coimmunoprecipitate appreciable levels of soluble receptors. These data indicate that D-1 dopamine receptors are coupled to both Gs alpha and G(o) alpha but not to Gq alpha. PMID- 7782332 TI - Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. AB - The identification of JAK2 as a growth hormone (GH) receptor-associated, GH activated tyrosine kinase has established tyrosyl phosphorylation as a signaling mechanism for GH. In the present study, GH is shown to stimulate tyrosyl phosphorylation of insulin receptor substrate 1 (IRS-1), the principle substrate of the insulin receptor. Tyrosyl phosphorylation of IRS-1 is a critical step in insulin signaling and provides binding sites for proteins with the appropriate Src homology 2 domains, including the 85-kDa regulatory subunit of phosphatidylinositol (PI) 3'-kinase. In 3T3-F442A fibroblasts, GH-dependent tyrosyl phosphorylation of IRS-1 was detected by 1 min and at GH concentrations as low as 5 ng/ml (0.23 nM). Tyrosyl phosphorylation of IRS-1 was transient, with maximal stimulation detected at 30 min and diminished signal detected at 60 min. The ability of GH receptor (GHR) to transduce the signal for IRS-1 tyrosyl phosphorylation is mediated by the intracellular region of GHR between amino acids 295 and 380 by a mechanism not involving the two tyrosines in this region. This region of GHR is required for GH-dependent JAK2 association and activation (VanderKuur, J. A., Wang, X., Zhang, L., Campbell, G. S., Allevato, G., Billestrup, N., Norstedt, G., and Carter-Su, C. (1994) J. Biol. Chem. 269, 21709 21717). When other cytokines that activate JAK2 were tested for the ability to stimulate the tyrosyl phosphorylation of IRS-1, stimulation was detected with interferon-gamma and leukemia inhibitory factor. The correlation between JAK2 tyrosyl phosphorylation and IRS-1 tyrosyl phosphorylation in response to GH, interferon-gamma, and leukemia inhibitory factor and in cells expressing different GHR mutants, provides evidence that IRS-1 may interact with JAK2 or an auxiliary molecule that binds to JAK2. GH is also shown to stimulate binding of IRS-1 to the 85-kDa regulatory subunit of PI 3'-kinase. The ability of GH to stimulate tyrosyl phosphorylation of IRS-1 and its association with PI 3'-kinase provides a biochemical basis for responses shared by insulin and GH including the well characterized insulin-like metabolic effects of GH observed in a variety of cell types. PMID- 7782331 TI - Low affinity binding of phorbol esters to protein kinase C and its recombinant cysteine-rich region in the absence of phospholipids. AB - Binding of phorbol esters to protein kinase C (PKC) has been regarded as dependent on phospholipids, with phosphatidylserine being the most effective for reconstituting binding. By using a purified single cysteine-rich region from PKC delta expressed in Escherichia coli we were able to demonstrate that specific binding of [3H]phorbol 12,13-dibutyrate to the receptor still takes place in the absence of the phospholipid cofactor. However, [3H]phorbol 12,13-dibutyrate bound to the cysteine-rich region with 80-fold lower affinity in the absence than in the presence of 100 micrograms/ml phosphatidylserine. Similar results were observed with the intact recombinant PKC delta isolated from insect cells. When different phorbol derivatives were examined, distinct structure-activity relations for the cysteine-rich region were found in the presence and absence of phospholipid. Our results have potential implications for PKC translocation, for inhibitor design, and for PKC structural determination. PMID- 7782333 TI - Interaction of platelet glycoprotein V with glycoprotein Ib-IX regulates expression of the glycoproteins and binding of von Willebrand factor to glycoprotein Ib-IX in transfected cells. AB - The goal of the present study was to determine whether platelet glycoprotein (GP) V interacts directly with the von Willebrand factor receptor GP Ib-IX and, if so, whether it affects the expression and function of this receptor. A melanoma cell line that does not contain actin-binding protein was transfected with the cDNAs coding for GP V and for each of the three subunits of GP Ib-IX. GP V co immunoprecipitated and co-localized with GP Ib-IX. Although GP V could be expressed in the absence of GP Ib-IX, the amount incorporated in the membrane was markedly increased when GP Ib-IX was present. Similarly, there was an enhanced expression of GP Ib-IX on the cell surface in the presence of GP V. The binding affinity of botrocetin-induced von Willebrand factor to GP Ib-IX was unaffected by the presence or absence of GP V. However, the binding capacity was increased by the presence of GP V. We conclude that GP V interacts directly with GP Ib-IX, that GP V must associate with GP Ib-IX to be efficiently expressed in the membrane, and that GP V increases the binding capacity of the cells for von Willebrand factor by enhancing the surface expression of the GP Ib-IX complex. PMID- 7782334 TI - Heterotetrameric complex formation of inositol 1,4,5-trisphosphate receptor subunits. AB - The inositol 1,4,5-trisphosphate receptor (IP3R) exists as a tetrameric complex to form a functional inositol 1,4,5-trisphosphate-gated Ca2+ channel. Molecular cloning studies have shown that there are at least three types of IP3R subunits, designated type 1, type 2, and type 3. The levels of expression of IP3R subunits in various cell lines were investigated by Western blot analysis using type specific antibodies against 15 C-terminal amino acids of each IP3R subunit. We found that all the three types of IP3R subunits were expressed in each cell line examined, but their levels of expression varied. To determine whether IP3Rs form heterotetramers, we employed immunoprecipitation experiments using Chinese hamster ovary cells (CHO-K1 cells), in which all three types are abundantly expressed. Each type-specific antibody immunoprecipitated not only the respective cognate type but also the other two types. This result suggests that distinct types of IP3R subunits assemble to form heterotetramers in CHO-K1 cells. We also detected heterotetramers in rat liver, in which IP3R type 1 and type 2 are expressed abundantly. Previous studies have shown some functional differences among IP3R types, suggesting the possibility that various compositions of subunits show distinct channel properties. The diversity of IP3R channels may be further increased by the co-assembly of different IP3R subunits to form homo- or heterotetramers. PMID- 7782335 TI - Accelerated hybridization of oligonucleotides to duplex DNA. AB - We report two strategies for accelerating the hybridization of oligonucleotides to DNA. We demonstrate that oligodeoxyribonucleotides and peptide nucleic acid oligomers hybridize to inverted repeats within duplex DNA by D-loop formation. Oligonucleotides and duplex template form an active complex, which can be recognized by T7 DNA polymerase to prime polymerization. Quantitation of polymerization products allowed the rate of hybridization to be estimated, and peptide nucleic acid oligomers and oligonucleotide-protein adducts anneal with association constants 500- and 12,000-fold greater, respectively, than the analogous unmodified oligonucleotides. Together, these results indicate that sequences within duplex DNA can be targeted by Watson-Crick base pairing and that chemical modifications can dramatically enhance the rate of strand association. These findings should facilitate targeting of oligomers for priming DNA polymerization, the detection of diagnostic sequences, and the disruption of gene expression. The observed acceleration of hybridization may offer a new perspective on the ability of RecA or other proteins to accelerate strand invasion. PMID- 7782337 TI - Altered carbohydrate recognition specificity engineered into surfactant protein D reveals different binding mechanisms for phosphatidylinositol and glucosylceramide. AB - Pulmonary surfactant protein D (SP-D) is a member of the collection subgroup of the C-type lectin superfamily that binds glycosylated lipids such as phosphatidylinositol (PI) and glucosylceramide (GlcCer). We have previously reported that the carbohydrate recognition domain of SP-D plays an essential role in lipid binding. However, it is unclear how the carbohydrate binding property of SP-D contributes to the lipid binding. To clarify the relationship between the lectin property and the lipid binding activity of rat SP-D, we expressed wild type recombinant rat SP-D (rSP-D) and a mutant form of the protein with substitutions Glu-321-->Gln and Asn-323-->Asp (SP-DE321Q,N323D) in CHO-K1 cells. The indicated mutations have previously been shown to change the carbohydrate binding specificity of surfactant protein A and mannose-binding protein from mannose > galactose to the converse. rSP-D expressed in mammalian cells was essentially identical to native rat SP-D in its lipid and carbohydrate binding properties. In contrast, SP-DE321Q,N323D was unable to bind GlcCer, but retained binding activity toward PI liposomes and solid-phase PI. The efficiency of SP DE321Q,N323D binding to PI liposome was approximately 50% of that of rSP-D in the presence of 5 mM Ca2+, but equivalent at 20 mM Ca2+. Carbohydrates competed for SP-D binding to PI such that maltose > galactose for rSP-D, and the order was reversed for SP-DE321Q,N323D. Furthermore, SP-DE321Q,N323D could bind to digalactosyldiacylglycerol more effectively than rSP-D. These results suggest the following. 1) The carbohydrate binding specificity of SP-DE321Q,N323D was changed from a mannose-glucose type to a galactose type; 2) the GlcCer binding property of SP-D is closely related to its sugar binding activity; and 3) the PI binding activity is not completely dependent on its carbohydrate binding specificity. PMID- 7782336 TI - The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck. AB - The Ras GTPase-activating protein (GAP) is a target for protein tyrosine kinases of both the receptor and cytoplasmic classes and may serve to integrate tyrosine kinase and Ras signaling pathways. In this report, we provide evidence that GAP is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase Hck, which has been implicated in the regulation of myeloid cell growth, differentiation, and function. Wild-type (WT) or kinase-inactive (K269E) mutant Hck proteins were co-expressed with bovine GAP using the baculovirus/Sf-9 cell system. GAP was readily phosphorylated on tyrosine by WT but not K269E Hck. GAP was present in WT Hck immunoprecipitates from the co-infected cells, indicative of Hck.GAP complex formation. Unexpectedly, GAP also associated with the kinase inactive mutant of Hck, suggesting that tyrosine autophosphorylation of Hck is not required for complex formation. The WT and K269E forms of Hck also associated with GAP mutants lacking either the C-terminal catalytic domain (delta CAT) or the Src homology region (delta SH), indicating that these GAP domains are dispensable for complex formation. Recombinant GST fusion proteins containing the Hck, Src, Fyn, or Lck SH3 domains associated with full-length GAP, delta CAT, and delta SH, all of which share an N-terminal proline-rich region resembling an SH3 binding motif (PPLPPPPPQLP). Deletion of the highly conserved YXY sequence from the Hck SH3 domain abolished binding. GAP-SH3 interaction was also inhibited by the proline-rich peptide GFPPLPPPPPQLPTLG, which corresponds to N-terminal amino acids 129-144 of bovine GAP. An N-terminal deletion mutant of GAP lacking this proline-rich region did not bind to the Hck SH3 domain. These data implicate the Hck SH3 domain in GAP interaction, and suggest a general function for the SH3 domains of Src family kinases in recognition of GAP via its proline-rich N terminal domain. PMID- 7782338 TI - Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. AB - We report cDNA cloning and characterization of the human and mouse orthologs of the chicken YAP (Yes-associated protein) gene which encodes a novel protein that binds to the SH3 (Src homology 3) domain of the Yes proto-oncogene product. Sequence comparison between mouse, human, and chicken YAP proteins showed an inserted sequence in the mouse YAP that represented an imperfect repeat of an upstream sequence. Further analysis of this sequence revealed a putative protein module that is found in various structural, regulatory, and signaling molecules in yeast, nematode, and mammals including human dystrophin. Because one of the prominent features of this sequence motif is two tryptophans (W), we named it the WW domain (Bork, P., and Sudol, M. (1994) Trends Biochem. Sci. 19, 531-533). Since its delineation, more proteins have been shown to contain this domain, and we report here on the widespread distribution of the WW module and present a discussion of its possible function. We have also shown that the human YAP gene is well conserved among higher eukaryotes, but it may not be conserved in yeast. Its expression at the RNA level in adult human tissues is nearly ubiquitous, being relatively high in placenta, prostate, ovary, and testis, but is not detectable in peripheral blood leukocytes. Using fluorescence in situ hybridization on human metaphase chromosomes and by analyzing rodent-human hybrids by Southern blot hybridization and polymerase chain reaction amplification, we mapped the human YAP gene to chromosome band 11q13, a region to which the multiple endocrine neoplasia type 1 gene has been mapped. PMID- 7782339 TI - Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging. AB - Oxidative modification of DNA, lipids, and proteins occurs as a consequence of reaction with free radicals and activated oxygen. Oxidative modification of total cellular proteins has been described under many pathologic and experimental conditions, but no specific proteins have been identified as in vivo targets for oxidative modification. Utilizing an immunochemical method for detection of oxidatively modified proteins, we identified a protein in rat liver that was highly oxidized. It was purified to homogeneity and identified as carbonic anhydrase, isozyme III. Its characteristics match those previously described for a protein that was lost during aging of the rat, senescence marker protein-1. Carbonic anhydrase III was purified from rats aged 2, 10, and 18 months, and the proteins were characterized. All three preparations were highly oxidatively modified as assessed by their carbonyl content. The enzyme has three known catalytic activities, and the specific activities for carbon dioxide hydration and for ester hydrolysis decreased during aging by approximately 30%. However, the third activity, that of a phosphatase, was virtually lost during aging. While the physiologic role of carbonic anhydrase III is unknown, we suggest that it functions in an oxidizing environment, which leads to its own oxidative modification. PMID- 7782341 TI - The hydroxy amino acid in an Asn-X-Ser/Thr sequon can influence N-linked core glycosylation efficiency and the level of expression of a cell surface glycoprotein. AB - N-Linked glycosylation usually occurs at the sequon, Asn-X-Ser/Thr. In this sequon, the side chain of the hydroxy amino acid (Ser or Thr) may play a direct catalytic role in the enzymatic transfer of core oligosaccharides to the Asn residue. Using recombinant variants of rabies virus glycoprotein (RGP), we examined the influence of the hydroxy amino acid on core glycosylation efficiency. A variant of RGP containing a single Asn-X-Ser sequon at Asn37 was modified by site-directed mutagenesis to change the sequon to either Asn-X-Cys or Asn-X-Thr. The impact of these changes on core glycosylation efficiency was assessed by expressing the variants in a cell-free transcription/translation/glycosylation system and in transfected tissue culture cells. Substitution of Cys at position 39 blocks glycosylation, whereas substitution of Thr dramatically increases core glycosylation efficiency of Asn37 in both membrane-anchored and secreted forms of RGP. The substitution of Thr for Ser also dramatically enhances the level of expression and cell surface delivery of RGP when the sequon at Asn37 is the only sequon in the protein. Novel forms of membrane-anchored and secreted RGP which are fully glycosylated at all three sequons were also generated by substitution of Thr at position 39. PMID- 7782340 TI - Isolation and characterization of gastric trypsin from the microsomal fraction of porcine gastric antral mucosa. AB - A gastric serine protease(s) was found in porcine gastric antral mucosa and was shown to be distributed in the endoplasmic reticulum (ER)-microsome fraction and also in the vesicle fraction. Two forms of the protease were purified over 6,000 fold from the ER-microsome fraction. Analyses of various molecular and enzymatic characteristics including the N-terminal and partial internal amino acid sequences of both forms revealed that they share the same properties and are indistinguishable from porcine pancreatic trypsin. This is the first time that trypsin or a protease almost identical with trypsin has been found to be present intracellularly in normal tissues. The gastric trypsin activities from the ER microsome and the vesicle fractions were located in distinct density regions upon density gradient centrifugation, which indicates association of the protease with different organelle membranes. Taken together, these results suggest that there may be a novel function of trypsin in the gastric mucosa; it might function as a specific degrading or processing enzyme as an intracellular protease. PMID- 7782342 TI - apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, is a novel RNA-binding protein. AB - Apolipoprotein B (apoB) mRNA editing is mediated by an enzyme complex which includes the catalytic subunit, apobec-1. Recombinant GST/APOBEC-1 binds with high specificity to a rat apoB RNA template as demonstrated by UV cross-linking and electrophoretic mobility shift assay (EMSA). ApoB RNA binding was competed by poly(U), poly(A,U), and tRNA, but not by poly(A) or other homopolymeric ribonucleotides. UV cross-linking of GST/APOBEC-1 to an apoB RNA template was uninfluenced by the binding of proteins of approximately 60 and approximately 44 kDa, present in S100 extracts prepared from different sources. The binding of these proteins was similarly uninfluenced by the simultaneous binding of GST/APO BEC-1. Moreover, the inclusion of heterologous S100 extracts in the RNA binding reactions completely abrogated the competitive displacement of GST/APOBEC-1 by tRNA. EMSA revealed the onset of RNA binding within 1-2 min, and its specificity was confirmed by a supershift with anti-GST/APOBEC-1 antisera. The structural specificity for apoB RNA binding, as inferred from EMSA, appears to be distinct from apoB RNA editing since wild-type chicken apoB RNA, which is not editable, and several mutant chicken apoB RNAs containing clustered mutations within the minimal apoB RNA editing cassette, bound with efficiency similar to the rat apoB RNA template. In conclusion, while the data suggest that apobec-1 binds AU-rich templates, the importance of this observation in the context of mammalian apoB mRNA editing remains unknown. PMID- 7782343 TI - Mutagenesis of apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, reveals distinct domains that mediate cytosine nucleoside deaminase, RNA binding, and RNA editing activity. AB - Apolipoprotein (apo) B48 is synthesized by mammalian small intestine as a result of post-transcriptional RNA editing. This process is mediated by an enzyme complex containing a catalytic subunit, apobec-1, which is homologous to other cytidine deaminases, particularly in a domain (H/C)-(A/V)-E-(X)24-30-P-C-(X)2-C which coordinates zinc, apobec-1, expressed as a glutathione S-transferase fusion protein, demonstrates both apoB RNA editing and cytidine deaminase activity. His61, Cys93, and Cys96, the putative zinc-coordinating residues, were mutated to Arg, Ser, and Ser, respectively, with loss of RNA editing activity and either great reduction or abolition of cytidine deaminase activity. Mutation of the catalytically active Glu63 residue to Gln and Pro92 to Leu abolished both cytidine deaminase and RNA editing activity. The conservative His61-->Cys mutation, which should coordinate zinc, retained both editing and cytidine deaminase activity. Thus, zinc binding is required for both apoB RNA editing and cytidine deaminase activity. Mutation of the first four leucines within the heptad repeat of the leucine-rich region (LRR) of apobec-1 resulted in reduced RNA editing but preservation of wild-type cytidine deaminase activity. GST/APOBEC 1 was also demonstrated to cross-link to apoB RNA. Mutation of His61-->Arg abolished RNA binding, while the Glu63-->Gln and Cys96-->Ser mutant proteins showed wild-type levels of RNA binding. The remaining mutants had reduced levels of activity. Overexpression of wild-type apobec-1 in McA 7777 cells resulted in a 5-6-fold increase in editing of endogenous apoB. Transfection of the His61-->Cys, LRR, and Cys93-->Ser mutants increased endogenous editing 2-3-fold, while Glu63- >Gln and His61-->Arg mutants acted as dominant negatives, reducing endogenous editing. These data suggest that apobec-1 has distinct functional domains which modulate activity in the context of the apoB mRNA editing enzyme. PMID- 7782344 TI - Intracellular A beta 1-42 aggregates stimulate the accumulation of stable, insoluble amyloidogenic fragments of the amyloid precursor protein in transfected cells. AB - We have analyzed the effect of internalized amyloid beta-protein (A beta) 1-42 aggregates on the metabolism of the amyloid precursor protein (APP) in stably transfected 293 cells. The amount of potentially amyloidogenic fragments of APP immunoprecipitated by anti-carboxyl-terminal APP and anti-A beta antibodies is dramatically enhanced by the treatment of the cells with A beta 1-42, which is resistant to degradation, but not A beta 1-28, which does not accumulate in cells. This accumulation of amyloidogenic carboxyl-terminal fragments is specific, since there is relatively little effect of A beta 1-42 on the amount of the nonamyloidogenic alpha-secretase carboxyl-terminal fragment. The amyloidogenic fragments accumulate in the same nonionic detergent-insoluble fraction of the cell that contains the internalized A beta 1-42. Western analysis indicates that a subset of the amyloidogenic fragments react with antibodies that recognize a conformation of A beta that is specifically associated with aggregated forms of A beta, suggesting that the adoption of this aggregation related conformation may be an early event which precedes the final processing that produces A beta. Pulse-chase analysis of the [35S]Met-labeled 16-kDa amyloidogenic fragment indicates that it is relatively stable in A beta 1-42 treated cells, with a half-life of approximately 50 h. This fragment is degraded with a half-life of 30 min in control cells treated with A beta 1-28. In contrast, the turnover of the nonamyloidogenic alpha-secretase product is not significantly altered by the presence of A beta 1-42. The continuous uptake of A beta 1-42 from the medium is not required for the stimulation of amyloidogenic fragment accumulation, suggesting that the presence of intracellular A beta 1-42 aggregates establishes a new pathway for APP catabolism in cells which leads to the long term stability of the fragments. If these amyloidogenic fragments of APP ultimately give rise to A beta, then the production of A beta may be an autocatalytic, "runaway" process in cells containing A beta 1-42 nuclei. It is conceivable that the accumulation of insoluble APP and amyloidogenic fragments of APP in response to A beta 1-42 aggregates may mimic the pathophysiology of dystrophic neurites, where the accumulation of intracellular APP and APP fragments has been documented by immunohistochemistry. PMID- 7782345 TI - The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits. AB - The cellular prion protein (PrPC) is a glycolipid-anchored protein that is involved in the pathogenesis of fatal spongiform encephalopathies. We have shown previously that, in contrast to several other glycolipid-anchored proteins, chPrP, the chicken homologue of mammalian PrPC, is endocytosed via clathrin coated pits in cultured neuroblastoma cells, as well as in embryonic neurons and glia (Shyng, S.-L., Heuser, J. E., and Harris, D. A. (1994) J. Cell Biol. 125, 1239-1250). In this study, we have determined that the N-terminal half of the chPrP polypeptide chain is essential for its endocytosis. Deletions within this region reduce the amount of chPrP internalized, as measured by surface iodination or biotinylation, and decrease its concentration in clathrin-coated pits, as determined by quantitative electron microscopic immunogold labeling. Mouse PrP, as well as two mouse PrP/chPrP chimeras, are internalized as efficiently as chPrP, suggesting that conserved features of secondary and tertiary structure are involved in interaction with the endocytic machinery. Our results indicate that the ectodomain of a protein can contain endocytic targeting information, and they strongly support a model in which the polypeptide chain of PrPC binds to the extracellular domain of a transmembrane protein that contains a coated pit localization signal in its cytoplasmic tail. PMID- 7782347 TI - The myristoylated amino terminus of ADP-ribosylation factor 1 is a phospholipid- and GTP-sensitive switch. AB - ADP-ribosylation factor 1 (Arf1) is an essential N-myristoylated 21-kDa GTP binding protein with activities that include the regulation of membrane traffic and phospholipase D activity. Both the N terminus of the protein and the N myristate bound to glycine 2 have previously been shown to be essential to the function of Arf in cells. We show that the bound nucleotide affects the conformation of either the N terminus or residues of Arf1 that are in direct contact with the N terminus. This was demonstrated by examining the effects of mutations in this N-terminal domain on guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) and GDP binding and dissociation kinetics. Arf1 mutants, lacking 13 or 17 residues from the N terminus or mutated at residues 3-7, had a greater affinity for GTP gamma S and a lower affinity for GDP than did the wild-type protein. As the N terminus is required for interactions with target proteins, we conclude that the N terminus of Arf1 is a GTP-sensitive effector domain. When Arf1 was acylated, the GTP-dependent conformational changes were codependent on added phospholipids. In the absence of phospholipids, myristoylated Arf1 has a lower affinity for GTP gamma S than for GDP, and in the presence of phospholipids, the myristoylated protein has a greater affinity for GTP gamma S than for GDP. Thus, N-myristoylation is a critical component in the construction of this phospholipid- and GTP-dependent switch. PMID- 7782346 TI - Two-hybrid system screen with the small GTP-binding protein Rab6. Identification of a novel mouse GDP dissociation inhibitor isoform and two other potential partners of Rab6. AB - Rab6 is a small GTP-binding protein that belongs to the Ras superfamily and is involved in intra-Golgi transport. Using a two-hybrid system screen of a mouse brain cDNA library, we have isolated several clones encoding proteins that interact with Rab6. Approximately 60% of the clones identified encoded a new mouse Rab GDP dissociation inhibitor (GDI) isoform. This GDI isoform is distinct from mouse mGDI-1 and mGDI-2, which have been characterized previously, and most likely represents the mouse counterpart of the rat Rab GDI beta isoform. In the two-hybrid system, GDI beta interacts with wild-type Rab6 and Rab5, but not with a GTP-bound Rab6 mutant, or a Rab6 mutant that cannot be post-translationally processed. We further examined whether mouse GDI beta is functional; we show that recombinant mouse GDI beta is able to remove several Rab proteins, including Rab1, Rab2, Rab4, and Rab6, from membranes. The identification of a third GDI isoform in mouse raised the question whether GDI genes belong to a larger multigenic family. We have shown, by Southern blot analysis of genomic DNA, that at least five GDI gene copies exist in both the mouse and rat genomes. In our two hybrid screen, we have also characterized another clone that specifically interacts with Rab6. This clone was partially sequenced but shows no homology to known sequences. Finally, a third clone, interacting with both Rab5 and Rab6, also appears to encode a novel protein. PMID- 7782348 TI - Differential activation of cytosolic phospholipase A2 (cPLA2) by thrombin and thrombin receptor agonist peptide in human platelets. Evidence for activation of cPLA2 independent of the mitogen-activated protein kinases ERK1/2. AB - The thrombin receptor agonist peptide SFLLRN was less effective than thrombin in eliciting the liberation of arachidonic acid and the generation of thromboxane A2 by human platelets. We found that while SFLLRN evokes an initial transient increase in cystolic free calcium concentration ([Ca2+]i) of similar magnitude as that caused by thrombin, the SFLLRN-induced elevation of [Ca2+]i declines more rapidly to near resting levels than that evoked by thrombin, suggesting that disparate levels of [Ca2+]i may contribute to the attenuated arachidonic acid release. Furthermore, we observed that SFLLRN is less effective than thrombin in mediating the "activating" phosphorylation of cytolic phospholipase A2 (cPLA2). Both thrombin and SFLLRN rapidly and transiently activated kinases that phosphorylate the 21-residue synthetic peptide Thr669 derived from the epidermal growth factor receptor, but the maximal activation of proline-directed kinases by SFLLRN was less pronounced than that by thrombin. MonoQ chromatography and immunoblot analysis of extracts from stimulated platelets revealed that while thrombin induced a prominent activation of the mitogen-activated protein kinases ERK1 and ERK2, SFLLRN completely failed to do so. On the other hand, SFLLRN, like thrombin, stimulated the activity of a proline-directed kinase distinct from ERK1/2, but the activation of this kinase was less pronounced following stimulation of platelets with SFLLRN compared with thrombin. We conclude 1) that the partial activation of cPLA2 and the subsequent attenuated mobilization of arachidonic acid in response to SFLLRN may be the consequence of a less prolonged elevation of [Ca2+]i and insufficient activation of proline-directed kinase(s) by SFLLRN and 2) that the ability of SFLLRN to mediate the activating phosphorylation of cPLA2 in the absence of ERK1/2 stimulation suggest that, at least in human platelets, proline-directed kinases other than ERK1/2 may phosphorylate and activate cPLA2. PMID- 7782349 TI - Phosphorylation of eukaryotic protein synthesis initiation factor 4E by insulin stimulated protamine kinase. AB - Insulin-stimulated protamine kinase (cPK) and protein kinase C (PKC) phosphorylated eukaryotic protein synthesis initiation factor 4E (eIF-4E) on serine and threonine residues located on an identical tryptic fragment as judged by two-dimensional phosphopeptide mapping. With cPK and PKC, the apparent Km for eIF-4E was about 1.2 and 50 microM, respectively. Relative to recombinant human eIF-4E, cPK exhibited about 100% and < or = 5% activity with eIF-4ES209A and eIF 4ET210A, respectively, and eIF-4ES209A was phosphorylated exclusively on threonines. Bovine kidney eIF-4E enhanced up to 1.8-fold globin synthesis in m7GTP-Sepharose-treated reticulocyte lysates. In contrast, following incubation with cPK, these eIF-4E preparations stimulated globin synthesis up to 6-fold. Compared to the dephosphorylation of the cPK-modified serine on eIF-4E, reticulocyte lysates and highly purified protein phosphatase 2A exhibited marked preference for the cPK-modified threonine. The results indicate that cPK phosphorylates eIF-4E on Ser209 and Thr210, that the hydroxyl group or phosphorylation of Thr210 is necessary for cPK to act on Ser209, and that Ser209 phosphorylation activates reticulocyte globin synthesis. The results suggest that cPK could contribute to the insulin-stimulated phosphorylation of eIF-4E, but that protein phosphatase 2A may confer the site specificity of this response. PMID- 7782350 TI - Hemolysin transport in Escherichia coli. Point mutants in HlyB compensate for a deletion in the predicted amphiphilic helix region of the HlyA signal. AB - The alpha-hemolysin transporter of Escherichia coli, a member of the ATP-binding cassette transporter super-family, is responsible for secretion of the 107-kDa protein toxin HlyA across both membranes of the Gram-negative envelope in a single step. Secretion of HlyA is dependent on a signal sequence, which occupies the C-terminal 50-60 amino acids of HlyA. Previously, it was shown that point mutants in the transmembrane domain of the transporter HlyB could partially correct the transport defect caused by a deletion of the C-terminal 29 amino acids of HlyA. These suppressor mutations demonstrated a direct interaction between HlyA and HlyB. They also displayed suppressor effects on a broad spectrum of HlyA signal mutants. In the present study, we selected HlyB alleles that complemented an internal deletion of 29 amino acids in HlyA containing a predicted amphiphilic helix region immediately upstream from the previous deletion. This set of HlyB mutants identifies further sites in HlyB that modulate substrate specificity but display allele-specific effects on a range of HlyA signal mutants. The inability to isolate mutations with effects restricted to either half of the signal sequence suggests that the signal is not recognized in a modular fashion by the transporter but rather functions as an integrated whole. We also report the isolation of the first substrate specificity mutation, which lies within the ATP-binding domain of HlyB. This could support a model in which the region of the ATP-binding cassette between the two Walker consensus motifs involved in ATP binding interacts with either the substrate or the transmembrane domains. PMID- 7782351 TI - Regions outside of the CAAX motif influence the specificity of prenylation of G protein gamma subunits. AB - A family of GTP-binding regulatory proteins (G proteins) transduces signals across the plasma membrane from a large number of receptors to a smaller number of effectors. Recent studies indicate that a series of post-translational modifications are required for their association with the plasma membrane and for their function. In the case of the G protein gamma subunits, the post translational modifications include the prenylation of a cysteine residue within a carboxyl-terminal CAAX motif. Although prenylation has been shown to involve the addition of either a C15 farnesyl or a C20 geranylgeranyl group to proteins, the structural requirements and functional consequences of adding different types of prenyl groups to various members of the gamma subunit family have not been examined. In the present study, we have employed the baculovirus expression system to study the structural requirements for attaching different types of prenyl groups to various members of the gamma subunit family. We show that the gamma 2 subunit is modified by a C20 geranylgeranyl group, consistent with the presence of a geranylgeranylation target sequence in this protein. However, we found that the gamma 1 and mutant gamma 2(Ser-71) subunits are modified by both C15 farnesyl and C20 geranylgeranyl groups, despite the presence of an accepted farnesylation target sequence in both of these proteins. Using chimeras of the gamma 1 and gamma 2 subunits, we provide evidence indicating that structural elements upstream of the carboxyl-terminal CAAX motif play a role in the recognition of members of the gamma subunit family by the appropriate insect and mammalian prenyltransferases. PMID- 7782352 TI - Induction of GADD153, a CCAAT/enhancer-binding protein (C/EBP)-related gene, during the acute phase response in rats. Evidence for the involvement of C/EBPs in regulating its expression. PMID- 7782354 TI - Prediction of progression of the curve in girls who have adolescent idiopathic scoliosis of moderate severity. Logistic regression analysis based on data from The Brace Study of the Scoliosis Research Society. AB - In a study conducted by the Scoliosis Research Society, 159 girls with a mean age of thirteen years (range, ten to fifteen years) who had adolescent idiopathic scoliosis were followed prospectively until skeletal maturity or until the curve had increased 6 degrees or more. All patients had had an initial curve of 25 to 35 degrees and an apical level between the eighth thoracic and first lumbar vertebrae, inclusive. Of the 159 patients, 120 were observed without treatment and thirty-nine were managed with lateral electrical surface stimulation. The curve progressed at least 6 degrees in eighty patients. There was no apparent difference in the outcome between the patients who were managed with observation only and those who were given electrical stimulation. Logistic regression analysis was performed to determine which of eleven factors were predictive of progression of the scoliotic curve. A Risser sign of 0 or 1, an apical level cephalad to the twelfth thoracic vertebra, and an imbalance of ten millimeters or less were found to be independently prognostic of progression of more than 6 degrees. A prognostic model that included these three factors and chronological age allowed correct classification of the curve as either progressive or non progressive in 81 per cent of these patients who had a thoracic or thoracolumbar adolescent idiopathic scoliosis. The positive predictive value was 82 per cent, the negative predictive value was 80 per cent, and the sensitivity and specificity were each 81 per cent. PMID- 7782353 TI - Effectiveness of treatment with a brace in girls who have adolescent idiopathic scoliosis. A prospective, controlled study based on data from the Brace Study of the Scoliosis Research Society. AB - In a prospective study by the Scoliosis Research Society, 286 girls who had adolescent idiopathic scoliosis, a thoracic or thoracolumbar curve of 25 to 35 degrees, and a mean age of twelve years and seven months (range, ten to fifteen years) were followed to determine the effect of treatment with observation only (129 patients), an underarm plastic brace (111 patients), and nighttime surface electrical stimulation (forty-six patients). Thirty-nine patients were lost to follow-up, leaving 247 (86 per cent) who were followed until maturity or who were dropped from the study because of failure of the assigned treatment. The end point of failure of treatment was defined as an increase in the curve of at least 6 degrees, from the time of the first roentgenogram, on two consecutive roentgenograms. As determined with use of this end point, treatment with a brace failed in seventeen of the 111 patients; observation only, in fifty-eight of the 129 patients; and electrical stimulation, in twenty-two of the forty-six patients. According to survivorship analysis, treatment with a brace was associated with a success rate of 74 per cent (95 per cent confidence interval, 52 to 84) at four years; observation only, with a success rate of 34 per cent (95 per cent confidence interval, 16 to 49); and electrical stimulation, with a success rate of 33 per cent (95 per cent confidence interval, 12 to 60).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782355 TI - Hip arthroplasty in hemophilic arthropathy. AB - As hemophilic arthropathy infrequently affects the hip joint, we performed a multicenter retrospective study to determine the results of hip arthroplasty in hemophilic patients. Thirty-four hip arthroplasties were performed in twenty seven male patients at four major hemophilia centers from October 1972 through September 1990. Twenty-six patients had classic hemophilia and one had factor-IX deficiency. The mean age of the patients at the time of the operation was thirty eight years (range, fifteen to seventy-three years). The mean duration of follow up was eight years, with a minimum of two years for all patients who were still alive at the time of this review. Four patients were seropositive for the human immunodeficiency virus at the time of the operation, and sixteen patients were seropositive at the time of the most recent follow-up examination. Nine patients (33 per cent) died before the time of this review; seven had been seropositive for the human immunodeficiency virus. There were twenty-six total hip arthroplasties performed with cement, six total hip arthroplasties performed without cement, one total hip arthroplasty in which the femoral component was inserted with cement and the acetabular component was inserted without it (so called hybrid arthroplasty), and one bipolar arthroplasty performed with cement. There were no early infections after these thirty-four primary arthroplasties. There were three late infections around prostheses inserted with cement, and all led to a resection arthroplasty. Six (21 per cent) of the twenty-eight cemented femoral components and six (23 per cent) of the twenty-six cemented acetabular components were revised because of aseptic loosening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782356 TI - Use of the Ilizarov technique for treatment of non-union of the tibia associated with infection. AB - Non-union of the tibia associated with infection was treated with radical resection of the necrotic bone and distraction osteogenesis in twenty-eight patients who were eighteen to seventy-four years old. Non-union, infection, shortening, deformity, and osteoporosis were all addressed simultaneously. All patients had either one-segment or two-segment lengthening of bone with a technique of bone transport in which a bone fragment is moved toward the site of non-union, leaving a defect that is bridged by distraction osteogenesis. The size of the bone defect that was bridged averaged six centimeters (range, two to thirteen centimeters). The infection was eradicated in all patients before the fixator was removed. The mean duration of treatment was ten months. The mean time to union, calculated from the day that the intercalary segment came into contact with the target segment, was six months. The mean duration of follow-up was thirty-nine months. The deformity and the inequality of the lengths of the legs were corrected successfully--to less than 7 degrees and to less than 2.5 centimeters, respectively--in fourteen of the twenty-eight patients. In these fourteen patients, the bone result--determined according to the criteria of union, healing of the infection, status of the deformity, and amount of residual shortening--was considered excellent. Of the fourteen remaining patients, eight had a good bone result; one, a fair result; and five, a poor result. The functional result was excellent in seven patients, good in eleven, fair in four, and poor in five. One patient had an amputation. Three patients (11 per cent) had a problem with union that was treated with augmentation with a bone graft. One patient, who had sustained a refracture, had an amputation. Twenty-five patients (89 per cent) had a total of seventy-one minor or major complications, a rate of 2.5 complications per patient. PMID- 7782357 TI - The tibiofibular syndesmosis. Evaluation of the ligamentous structures, methods of fixation, and radiographic assessment. AB - Twenty-five fresh-frozen cadaveric specimens were used to evaluate the role of the syndesmotic ligaments when the ankle is loaded with external rotation torque. An apparatus was constructed that allowed pure external-rotation torque to be applied through the ankle with the foot in neutral flexion. The apparatus provided solid fixation of the tibia while allowing free movement of the fibula in all planes. The syndesmotic ligaments were incrementally sectioned, and direct measurements of anatomical diastasis were made. Mortise and lateral radiographs were made at each increment under both loaded (5.0 newton-meters) and unloaded conditions. After all structures of the syndesmosis had been divided, the syndesmosis was reduced and was repaired with one or two screws. The strength of the repair was measured with incremental increases in torque of 1.0 newton-meter. The radiographs were measured by three independent observers in a blind fashion. In order to evaluate intraobserver error, each observer was randomly given forty radiographs to reinterpret. Diastasis and rotation were found to be related to the amount of injury of the ligament (p < 0.0001). After the entire syndesmosis had been divided, application of a 5.0-newton-meter torque resulted in a mean diastasis of 7.3 millimeters. The subsequent repair of the anterior tibiofibular ligament with suture failed at a mean of 2.0 newton-meters (range, 1.0 to 6.0 newton-meters) of torque. Repair with two screws was found to be stronger than repair with one, with the first construct failing at a mean of 11.0 newton-meters (range, 5.0 to 15.0 newton-meters) and the second, at a mean of 6.2 newton-meters (range, 2.0 to 10.0 newton-meters) (p = 0.0005). Failure of the screw fixation was not associated with the maximum previous diastasis (p = 0.13). Measurements of anatomical diastasis were compared with measurements made on the mortise and lateral radiographs. Measurements on the stress mortise radiographs had a weak correlation with diastasis (r = 0.41, p < 0.0001). However, measurements on the stress lateral radiographs had a higher correlation (r = 0.81, p < 0.0001). Additionally, interobserver correlation was significantly higher for the measurements on the lateral radiographs (r = 0.87, p < 0.0001) than for those on the mortise radiographs (r = 0.56, p < 0.0001). Intraobserver correlation for the three observers was poor with regard to the measurements on the mortise radiographs (r = 0.12, 0.42, and 0.25). The respective correlations for the measurements on the lateral radiographs were r = 0.81, 0.90, and 0.89.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7782358 TI - Debridement of degenerative, irreparable lesions of the rotator cuff. AB - A modified Neer acromioplasty, subacromial decompression, and debridement of massive, irreparable lesions of the supraspinatus and infraspinatus tendons was performed in fifty-seven patients. Fifty patients (fifty-three shoulders) were followed for an average of six and one-half years. The average age of the patients was sixty years (range, thirty-eight to seventy-four years). The results, as rated on the basis of pain, function, range of motion, strength, and satisfaction of the patient, were satisfactory in forty-four shoulders (83 per cent) and unsatisfactory in nine (17 per cent). A favorable outcome was observed in shoulders in which both the anterior portion of the deltoid muscle and the long head of the biceps tendon were intact and in which a previous acromioplasties or operations on the rotator cuff had been performed. An unsatisfactory outcome was observed in shoulders in which the anterior part of the deltoid muscle was weak or absent or in which a previous acromioplasty and attempted repair of the rotator cuff had been performed. The active forward flexion of the shoulder improved from an average of 105 degrees preoperatively to an average of 140 degrees postoperatively. The results of the present study suggest that, with proper rehabilitation, adequate decompression of the subacromial space, anterior acromioplasty, and debridement of massive tears of the rotator cuff can lead to the relief of pain and the restoration of shoulder function. PMID- 7782359 TI - The thoracolumbar spine in Marfan syndrome. AB - We analyzed the prevalence, inheritance, progression, and functional implications of spinal deformity in Marfan syndrome using four different groups of patients. We studied 113 patients who had Marfan syndrome, eighty-two of whom were skeletally immature, in order to characterize the alignment and function of the spine. The patients were selected from a clinic that provides total care with no bias toward the presence of orthopaedic conditions. Scoliosis was identified in fifty-two of the eighty-two patients, and the prevalences for the sexes were equal. The thoracic portion of the curve was convex to the right in all but two patients. The mean kyphosis was greater than that in the general population. Five distinct sagittal profiles were identified on the basis of whether the thoracic kyphosis was within, greater than, or less than normal limits and whether the transition between the kyphosis and lordosis occurred at or caudad to the normal level or whether the curves were reversed. Spondylolisthesis was present in five patients (6 per cent), with a mean slip of 30 per cent. Fourteen pedigrees were studied in depth. There was no familial pattern of the scoliosis. A separate group of fifty-six patients with scoliosis, for whom serial follow-up radiographs were available, was studied for progression. Patients who had a curve of more than 30 degrees had mild progression, and those who had a curve of more than 50 degrees had marked progression (mean, 3 +/- 4 degrees per year). Pain and function of the back were studied in thirty patients who were thirty-five to forty-five years old; these patients were found to be more impaired than matched controls. The presence of scoliosis was associated with pain in the region of the curve in these patients. PMID- 7782360 TI - Rate of degeneration of human acetabular cartilage after hemiarthroplasty. AB - Biopsy specimens of cartilage and subchondral bone were obtained from the weight bearing dome of the acetabulum in twelve elderly patients who were having a revision of a hemiarthroplasty of the hip because of pain. Biopsy specimens of acetabular cartilage and subchondral bone were also obtained from eight patients of comparable age who were having a primary hemiarthroplasty for a displaced fracture of the femoral neck; these served as the control specimens. The specimens were stained with hematoxylin and eosin for the initial histological assessment of cartilage structure and cellularity as well as the integrity of the tidemark. Safranin-O and toluidine-blue stains were used to assess proteoglycan content. A histological grading scale was employed for comparative analysis of samples. The joint space of the hip was measured on the radiographs that were made before the revision and was correlated with the histological grade. Review of the histological specimens demonstrated considerable degeneration of acetabular cartilage in the patients who were having a revision of a hemiarthroplasty as compared with that in the age-matched control patients who were having a primary hemiarthroplasty. The progression in the severity of the degeneration correlated directly with the duration of articulation of the implant with the acetabulum. All six of the patients in whom the implant had been in situ for more than five years, and in whom the femoral stem was determined to be stable at the operation, had nearly complete loss of cartilage as seen on histological examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782361 TI - Non-union of the scaphoid. Revascularization of the proximal pole with implantation of a vascular bundle and bone-grafting. AB - Eleven patients who had an ununited fracture of the scaphoid associated with loss of the blood supply to the proximal fragment were managed operatively with a combination of an inlay corticocancellous bone graft from the iliac crest and implantation of the second dorsal intermetacarpal artery, its accompanying venae comitantes, and a thin cuff of perivascular tissue. The absence of the blood supply to the proximal pole was evidenced both by radiographic changes--which included increased bone density, absence of normal trabeculae, and cystic changes -and by failure to observe bleeding bone during the operation. There were ten men and one woman. The average duration of non-union was fourteen months (range, six to thirty-three months). Six patients had had previous unsuccessful operative attempts to obtain union. Eight non-unions were in the proximal one-third and three, at the waist of the scaphoid. Union was achieved in ten patients at an average of ten weeks postoperatively. According to the wrist-scoring system of the Mayo Clinic, at an average of five years (range, 2.5 to eleven years), three patients had a grade of excellent; three, good; three, fair; and two, poor. Four patients had subsequent reconstructive procedures; radial styloidectomy, styloidectomy and resection of osteophytes, radioscapholunate arthrodesis, and total wrist arthrodesis were performed in one patient each. PMID- 7782362 TI - Operative treatment of malunited fractures of the forearm. AB - We conducted a retrospective review of the results of twenty-seven consecutive osteotomies for malunited fractures of the forearm performed at the Mayo Clinic from 1976 to 1991. There were seventeen male patients and ten female patients who were an average of nineteen years old (range, nine to forty-one years old) at the time of the osteotomy. The corrective osteotomy was performed an average of seventy-three months (range, two to 324 months) after the fracture. The indication for the procedure was functional loss of motion (average arc of pronation-supination, 74 degrees; range, 20 to 120 degrees) in twenty patients, an unstable and painful distal radioulnar joint in six, and an unacceptable appearance of the forearm in one. Twenty patients had a corrective osteotomy of the radius; two, of the ulna; and five, of both bones. Of the twenty patients who had a corrective osteotomy for loss of motion of the forearm, nine were managed within twelve months after the initial injury and eleven were managed more than twelve months afterward. The patients who were managed early gained an average of 79 degrees (range, 20 to 160 degrees) of rotation after the osteotomy. Those who were managed late gained an average of only 30 degrees (range, -25 to 95 degrees). A pain-free, stable wrist was achieved in three of the six patients who were managed for an unstable and painful distal radio-ulnar joint. However, these six patients lost an average of 7 degrees (range, -25 to 25 degrees) of rotation of the forearm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782364 TI - Mechanical consequences of bone ingrowth in a hip prosthesis inserted without cement. AB - Long-term biomechanical problems associated with the use of sintered porous coating on prosthetic femoral stems inserted without cement include proximal loss of bone and a risk of fatigue fracture of the prosthesis. We sought to identify groups of patients in whom these problems are accentuated and in whom the use of porous coating may thus jeopardize the success of the arthroplasty. We attempted to develop clinical guidelines for the use of sintered porous coating by investigating the long-term biomechanical effects of bone growth into partially (two-thirds) porous-coated anatomic medullary locking hip prostheses that fit well. More specifically, we used a detailed finite element analysis and a composite beam theory to determine the dependence of proximal loading of the bone and maximum stresses on the stem on the development of clinically observed patterns of bone ingrowth and the dependence of the risk of fatigue fracture of the stem on the diameter of the stem, the diameter of the periosteal bone, and the material from which the prosthesis was made. We found that bone ingrowth per se substantially reduced proximal loading of the bone. With typical bone ingrowth, axial and torsional loads acting on the proximal end of the bone were reduced aa much as twofold compared with when there was no ingrowth; bending loads on the proximal end of the bone were also reduced. The risk of fatigue fracture of the stem was insensitive to the development of bone ingrowth. However, the risk of fatigue fracture of the stem increased with decreased diameters of the stem and the periosteal bone and with increased modulus of the stem. The maximum risk of fracture was found in active patients in whom a cobalt chromium-alloy stem with a small diameter had been implanted in a bone with a small diameter. PMID- 7782366 TI - Prostaglandin-induced cortical hyperostosis. Case report and review of the literature. PMID- 7782365 TI - Treatment of supracondylar fractures of the femur proximal to a total knee arthroplasty. A report of four cases. PMID- 7782363 TI - Evaluation of bone ingrowth in proximally and extensively porous-coated anatomic medullary locking prostheses retrieved at autopsy. AB - Three proximally (40 per cent) and five extensively (80 per cent) porous-coated anatomic medullary locking femoral components were retrieved from seven cadavera at autopsy. Each component (with the surrounding, intact femur), was sectioned transversely at one-centimeter intervals. Backscattered scanning electron microscopy was used to evaluate circumferentially the interface between the bone and the porous surface of each section. Bone ingrowth was considered to be present within a field when bone was in contact with the outermost layer of the sintered beads, it was detected within the porous space, and it had penetrated the porous space to a depth of at least one bead diameter. All eight components had some bone growth into the porous space. A mean of 35 per cent of the surface of the implants had bone ingrowth. In the areas where bone was present, 67 per cent of the available porous space on the extensively coated stems and 74 per cent on the proximally coated stems contained bone. With both types of implants, the greatest amount of compact bone ingrowth was found at the level where the porous coating ended. Transverse sections obtained at this level frequently demonstrated that bone ingrowth had occurred circumferentially and that the ingrowth was continuous with and an integral part of the femoral cortex. These direct connections to the cortex could be predicted from the appearance of the radiographs. In the most proximal transverse sections of both types of implants, bone was most frequently connected to the medial side and corners of the implant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782367 TI - Methemoglobinemia: a complication after fiberoptic orotracheal intubation with benzocaine spray. A case report. PMID- 7782369 TI - The importance of the posterior oblique ligament in repairs of acute tears of the medial ligaments in knees with and without an associated rupture of the anterior cruciate ligament. Results of long-term follow-up. PMID- 7782368 TI - Enhancement of fracture-healing. PMID- 7782370 TI - The importance of the posterior oblique ligament in repairs of acute tears of the medial ligaments in knees with and without an associated rupture of the anterior cruciate ligament. Results of long-term follow-up. PMID- 7782371 TI - Issues related to clinical pathways: managed care, implementation, and liability. PMID- 7782372 TI - Critical pathways: what they are and what they are not. PMID- 7782373 TI - Steps to pathway development. PMID- 7782376 TI - Utilizing critical pathways to facilitate continued quality improvement. PMID- 7782375 TI - Development of burn outcomes and quality indicators. A project of the ABA Committee on Organization and Delivery of Burn Care. PMID- 7782374 TI - Designing tools for pathway implementation and evaluation. PMID- 7782377 TI - Utilization of critical pathways to facilitate clinical care. PMID- 7782378 TI - Utilization of critical pathways in education. PMID- 7782379 TI - Critical pathways in research. PMID- 7782380 TI - [Laparoscopic surgery: injuries caused by trocars. (French Survey 1994) in reference to 103,852 interventions]. AB - In a French retrospective survey including 103,852 laparoscopic procedure, and 390,000 port-insertion, trocar injuries rate have been evaluated. Mortality is 0.07 per thousand, quite exclusively in relation with vascular injuries (especially from aorta and iliac vessels) with a rate of 0.4 per thousand. All intra-abdominal viscera and vessels must be injured by the first blind trocar insertion. Open laparoscopy is systematically proposed to prevent these accidents. PMID- 7782381 TI - [Left single-lobe Caroli disease discovered during intraoperative cholecystography ... or how a routine cholecystectomy can lead to left hepatectomy]. AB - The authors report a case of single-lobe Caroli's disease discovered at the radiologic exploration during a laparoscopic cholecystectomy leading to a left hepatic lobectomy 2.5 months later. Localized dilatation of the intrahepatic bile ducts are infrequent. They may be associated with others pathological conditions such as cystic dilatation of the extrahepatic bile-ducts, congenital hepatic fibrosis of the liver or renal pathology. Hepatic resection is the logical treatment of such localized lesions, but it may have an excessive risk in case of association with a congenital hepatic fibrosis of the liver. The authors insist about the necessity of radiographic exploration during every biliary surgical approach, even with laparoscopic technic. PMID- 7782382 TI - [Retro-duodenal papillary perforation after endoscopic sphincterotomy. Role of surgical treatment by exclusion of the duodenum. Apropos of 3 cases]. AB - Among the complications of endoscopic sphincterotomy whose rate is about 10% of cases, the retroduodenal papillary perforation represents about 1% of cases. The diagnosis lies on radiological examination which may show during the sphincterotomy the extravasation of the contrast fluid used for the retrograde cholangiography; it can be suggested by the presence of clinical signs of retroperitoneal sepsis or peritonitis. The treatment depends on the severity or peritonitis. The treatment depends on the severity of the clinical symptomatology; it is generally a medical treatment associating nasogastric aspiration and antibiotherapy, and more rarely a surgical one. There is no consensus concerning surgical modalities. We report 3 cases of retroduodenal papillary perforation treated surgical by a duodenal exclusion aiming to transform a complex fistula in a bilio-pancreatic fistula which can be more easily managed by somatostatine-like drugs. PMID- 7782383 TI - [Hospital procedures and surgical management of patients with stab wounds to the heart]. AB - Stab wounds of the heart are frequent: one case every two and a half months in our service. In our series of 9 cases, only three were alive at arrival to the emergency ward, but in all of these three, treatment was simple requiring only simple wound suture without extra-corporeal circulation. Based on our experience and the data in the literature, we propose cooperation between three teams for managing these patients: anaesthesists, echocardiographists and cardiothoracic surgeons. The patients are admitted directly to the cardiothoracic operating theatre where the echocardiographist and the surgery team take charge. The surgical procedure depends on the general situation and especially on whether or not the echocardiologist can confirm haemopericardium immediately. Every patient with possible wound to the heart or major vessels should be managed directly by the cardiothoracic surgery team before of formal diagnosis has been established. PMID- 7782384 TI - [Ureteral trauma during surgery for aneurysm of the subrenal abdominal aorta. Apropos of 2 complete sections discovered postoperatively]. AB - The lombo-iliac ureter is particularly exposed in surgery of the aorta, particularly for bypass surgery and cure of aneurysms. Two recent cases of complete section of the ureter were discovered post-operatively. Endo-urologic techniques offer a promising means of protecting the upper urinary tract in these procedures. Percutaneous nephrostomy and ureteral catheterism have also been discussed as have been ureteral endoprosthesis and double J ureteroscopy. PMID- 7782385 TI - [Cancer of the breast in men. Apropos of 50 cases]. AB - Breast cancer, rarely encountered in men, accounts for 0.2 to 1.5% of the cancer morbidity in men and 1 to 5.7% of all breast cancers. The aim of this work is to analyse the different epidemiological, therapeutic and outcome features of this disease in men using a retrospective multicentric approach to 50 cases reported in Casablanca from 1980 to 1992. The mean age of the patients was 60.6 years. No significant risk factor was found. The mean delay to consultation was 22.5 months. Diagnosis was made at an advanced stage as, the tumour was located behind the nipple in 98% of the cases and ulcerated in 52%. Laterality was almost identical. Invasive galactophoric adenocarcinoma was found in 86% of the cases. Treatment was usually Patey mastectomy with positive nodes in 84%. Complementary treatment included radiotherapy in 60%, chemotherapy in 36% and hormonotherapy in 1 case. Recurrence was observed in 71% of the patients who has achieved complete remission. Surviceal in evaluable cases was 59 and 25% at 2 and 5 years respectively. The results in this series was less satisfactory that it is generally reported in the literature which suggests the need for better codification and management. PMID- 7782386 TI - [Stenosis of the rectum secondary to an invasive adenocarcinoma of the prostate. Apropos of 3 cases]. AB - There exist rare cases in which a prostatic carcinoma invades the perirectal space producing an extrinsic rectal stenosis. Three cases are discussed. Differential diagnosis with a rectal tumor is difficult clinically, but endorectal ultrasound and deep rectal biopsies must provide the correct diagnosis in most cases. Hormonotherapy is recommended, but prognosis is reserved. PMID- 7782387 TI - [Evaluation and treatment of closed traumas of the kidney]. AB - On the basis of a series of fifty-one blunt renal injuries and a review of literature, the characteristics of this affection are reviewed. This trauma typically occurs in young adults. Minor injuries are the most frequent (75.5 percent) and associated lesions are not rare. Computed tomography is the imaging technique of choice for renal trauma assessment. It can, sometimes, be replaced by urography-ultrasonography couple. Indications of these imaging modalities are reviewed. A classification in four types, adapted to new imaging methods, is proposed to harmonize or to compare therapeutic indications. The different therapeutic methods, their indications and their particularities are studied and a simple decisional strategy is proposed. PMID- 7782388 TI - [Rare association of a non-functional retroperitoneal paraganglioma and nephrotic syndrome]. AB - Non functional retroperitoneal paragangliomas are rare: less than 50 cases in literature. They are usually asymptomatic and can attain reasonable dimensions. The association with nephrotic syndrome is exceptional. The authors report a clinical observation of non-functional paraganglioma in a 45 year old woman, with repeated surgical abstention. Literature was reviewed and therapeutic indications discussed. PMID- 7782389 TI - [Degenerative colorectal polyps]. AB - In 23 patients with malignant colorectal polyps we reviewed the frequency of recurrence. In the group without subsequent local resection, 8 of 11 patients were without recurrent tumour after 2.7 (0.8-4.1) years, in the group with subsequent local or conventional colon resection, 10 of 12 patients after 5.3 (0.8-9.0) years. None of the patients showed any evidence of residual tumour or lymph node metastasis. All recurrent tumours (2 x carcinoma, 3 x benign polyps) could be resected curatively. There was no difference in recurrence in both groups. For safe histopathological examination of malignant colorectal polypi in respect of depth of invasion, free resection margins and lymphatic vessel invasion, intraoperative fixation and marking must be performed, since local recurrence was seen after more than 5 years, long-term follow up is necessary. PMID- 7782390 TI - [Evolution of the legal concept of surgical responsibility]. PMID- 7782391 TI - Chest pain and ST-segment elevation. PMID- 7782392 TI - Aggressive volume expansion and pseudo-ARDS. PMID- 7782393 TI - Case in point. Systemic amyloidosis. PMID- 7782394 TI - Managing the difficult patient. PMID- 7782395 TI - Smoking cessation: lights out. PMID- 7782396 TI - Jaundice and massive abdominal lymphadenopathy. PMID- 7782397 TI - Angioplasty in acute myocardial infarction. AB - The results of early trials indicate that angioplasty during the first hours after MI onset has a lower incidence of reinfarction, intracranial hemorrhage, and death than does thrombolysis. In fact, results have been so good that the procedure has been approved for use in hospitals that do not have coronary bypass backup programs. Is angioplasty about to become the intervention of choice in acute MI? PMID- 7782398 TI - Islet cell transplantation for insulin-dependent diabetes. AB - About 20 years after investigators began work on the isolation of animal islets, we are now poised to use such cells to control blood sugar levels in humans. Studies in various laboratories have led to development of transplantation techniques that obviate the need for chronic immunosuppression; equally important, the techniques also appear to avoid the problem of graft rejection. PMID- 7782399 TI - Abdominal pain in a diabetic woman. PMID- 7782400 TI - Recognition and management of occult alcohol withdrawal. AB - Many patients experience withdrawal because an acute illness has interrupted their usual alcohol intake. Medical and psychiatric complications of alcoholism may also coexist with withdrawal. Several findings predict the likelihood of seizures of delirium tremens and thus are useful in making initial treatment decisions. PMID- 7782402 TI - Annotation: long-term outcomes of developmental reading problems. PMID- 7782401 TI - Managing medication in the elderly. AB - The elderly receive 30% of all prescriptions and buy 40% of all OTC drugs. In addition to the potential pitfalls inherent to age-related changes in bioavailability and clearance, there are less well-known hazards in prescribing for the aged. Many drugs, for example, have powerful anticholinergic properties, and a generic agent may differ markedly from both the brand drug and another generic version. PMID- 7782403 TI - Practitioner review: verbal working memory development and its disorders. AB - Working memory refers to the systems responsible for the temporary storage and manipulation of information during the performance of cognitive tasks. There is a good deal of evidence that verbal short-term memory functions as a working memory system. We review advances in our understanding of the nature and limitations of verbal short-term memory and the reasons for its development with age, and go on to consider the common association between impairments of verbal short-term memory and other impairments of cognitive development. We conclude by considering the relationship between short-term memory development and cognitive development. PMID- 7782404 TI - A comparison of phonological skills in children with reading comprehension difficulties and children with decoding difficulties. AB - This paper examines phonological skills in children with two distinct forms of reading difficulty: comprehension problems and decoding problems. In the first study a group of children with normal decoding skills but poor reading comprehension skills was studied. These children were found to have age appropriate phonological skills. It is argued that normal phonological skills have enabled them to develop proficient decoding skills. A second study assessed the phonological skills of a group of children with decoding difficulties. These children showed marked deficits on tests of phonological skills. It appears that weak phonological skills underlie these children's decoding difficulties. PMID- 7782405 TI - The impact of child IQ, parent IQ and sibling IQ on child behavioural deviance scores. AB - In an epidemiological sample of 411 13-year-old twins of normal intelligence, both parents and teachers reported more behavioural problems among children with lower IQs. This was not attributable to the effects of parental IQ or social class and was not entirely mediated by lower scholastic attainments. Different causal models are discussed: "rater bias" and "IQ is a consequence" explanations seem less plausible than "IQ is a cause" and "IQ is a marker" explanations. Higher parental IQ was associated with more emotional symptoms in the child, both by parental and school report. There was no evidence that being brighter or less bright than a (twin) sibling influenced behavioural deviance, casting doubt on the importance of contrast effects. PMID- 7782406 TI - The significance of self-reported anxious symptoms in first grade children: prediction to anxious symptoms and adaptive functioning in fifth grade. AB - In an earlier study of an epidemiologically defined sample of first grade children, primarily between the ages of 5 and 6, self-reported anxious symptoms proved relatively stable and were significantly related to adaptive functioning. In the present study we follow that cohort of first graders longitudinally and assess the prognostic value of self-reports of anxious symptoms in first grade with respect to anxious symptoms and adaptive functioning in the late elementary school years or at about age 10. First grade anxious symptoms were found to have significant prognostic value in terms of levels of anxious symptoms and adaptive functioning in fifth grade. PMID- 7782407 TI - Are anxiety symptoms in childhood heritable? AB - Although childhood anxiety appears to aggregate in families, transmission could be explained by both genetic and shared environmental factors. Twin studies can be used to disentangle genetic and environmental effects. In this study, a systematically ascertained sample of twins was used to investigate whether anxiety symptoms are heritable. Parent-rated anxiety symptoms could best be explained by an additive genetic model with heritability estimated at 59%. However, when self ratings were analysed (in the adolescent subsample), familial transmission could be accounted for by shared environmental factors only. PMID- 7782408 TI - A twin-singleton comparison of problem behaviour in 2-3-year-olds. AB - Twin-singleton differences in problem behaviours in 2-3-year-olds were studied. Maternal ratings of children's problem behaviours were obtained with the CBCL/2 3. The twin sample consisted of 1363 twin pairs (456 MZ, 907 DZ), the sample of singletons consisted of 420 children from the general population. Results indicated that the general level of problem behaviours in twins was broadly comparable to that in singletons. Four of the seven syndromes showed lower scores for twins. These differences, however, were small and mainly caused by lower scores for DZ twins in comparison to MZ twins and singletons. Part of the difference could be attributed to the higher maternal age in the twin groups. Higher means for boys were found for the total problem score, and the Aggressive and Overactive syndromes. PMID- 7782409 TI - Deafness, conversation and theory of mind. AB - The child's developing theory of the mind as an interconnected network of beliefs, desires and feelings that govern behaviour provides a cornerstone for social and intellectual life. Recent research has suggested that autistic children have difficulty acquiring such a theory. Although it is speculated that a specific neurological deficit may be responsible for autistic children's difficulties on false belief tasks devised to test a theory of mind, these may also be due to a lack of exposure to conversation about mental states. In this study we explored the development of a theory of mind in a group of 26 signing, prelingually-deaf Australian children of normal intelligence, aged 8-13 years. Results revealed that 65% of these deaf children failed a simple test of false belief which normal preschoolers, mentally retarded children, and other handicapped groups--apart from children with autism--routinely pass at a mental age of 4-5 years. No significant difference emerged between deaf children's performance and that of autistic children tested on the same task in previous research. We discuss the results in terms of a conversational account of the development of a theory of mind in deaf children, and the extent to which this account is applicable to children with autism. PMID- 7782410 TI - Emotional role-taking abilities of children with a pervasive developmental disorder not otherwise specified. AB - Seven to 12-year-old children with a Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) were compared with normal, healthy children of the same age and sex on three different emotional role-taking tasks. In these tasks, children had to use person-specific information to make an inference about another child's emotional reaction and behaviour, Significant differences were found between the PDDNOS group and control group: PDDNOS children performed worse on all three role-taking tasks. However, the differences on one of these tasks could be completely explained by intelligence differences between the two groups. On the other tasks, differences could not or be partially explained by intelligence differences. The results of this study led to the formulation of a more specific hypothesis, namely that PDDNOS children might have problems interpreting social information when affectively charged background information has to be used. PMID- 7782411 TI - Contributing factors in the manifestation of aggression in preschoolers with hyperactivity. AB - This study examined family characteristics of preschoolers with hyperactivity. We assessed child-rearing practices, maternal depression, marital conflict, and social support. Sixty-three preschool boys were placed in a hyperactivity aggressive, hyperactive, aggressive or comparison group based on behavioral ratings. Parents were given questionnaires, mothers were interviewed, and children were administered the Woodcock-Johnson Psycho-Educational Battery and were observed playing. Compared to preschoolers with hyperactivity, preschoolers with hyperactivity plus aggression had families with (a) more restrictive fathers, (b) siblings who retaliated aggressively, and (c) mothers who reported more physical aggression directed to their partners and more verbal aggression received. Follow-forward aggression ratings were predicted by initial child manageability and maternal depression, perceived support, and low income. PMID- 7782412 TI - The sex ratios of families with a neurodevelopmentally disordered child. AB - It has been conjectured that mothers who give birth to neurodevelopmentally disordered (ND) children may have hormonal or immunological characteristics that bias them toward giving birth to male children. We examined this hypothesis in an epidemiological sample of 2,080 ND children drawn for the National Collaborative Perinatal Project (NCPP) who had one of nine kinds of NDs. No assumptions were made regarding the sex ratio of non-ND children since this could be computed from NCPP data for 11,213 families. The sex ratio of families with ND children was not significantly biased toward boys as compared to the sex ratio of families with non-ND children, provided that the index ND child was excluded from the analysis. PMID- 7782413 TI - ICSI and severe male-factor infertility: breaking the sperm tail prior to injection. PMID- 7782414 TI - Intracytoplasmic injection of testicular and epididymal spermatozoa for treatment of obstructive azoospermia. PMID- 7782415 TI - The R.A.P.R.U.I. Center experience: from SUZI, through lasers to ICSI using spermatozoa with broken tails. PMID- 7782416 TI - ICSI of unfertilized oocytes after IVF insemination: are the traditional markers of fertilization adequate? PMID- 7782418 TI - Systematic examination of immobilizing spermatozoa before intracytoplasmic sperm injection in the human. PMID- 7782417 TI - Intracytoplasmic sperm injection versus high insemination concentration in-vitro fertilization in cases of very severe teratozoospermia. PMID- 7782419 TI - Autoreproduction by hermaphrodites. PMID- 7782420 TI - Fertilization of an oocyte microinseminated with a spermatid in an in-vitro fertilization programme. PMID- 7782421 TI - What forms of male infertility are there left to cure? PMID- 7782422 TI - Human tubal fluid: formation and composition during vascular perfusion of the fallopian tube. AB - A vascularly perfused preparation of the Fallopian tube has been developed as a model to study the formation and composition of human tubal fluid. An artery serving the tube was cannulated and perfused at a rate of 0.7 ml/min for 1 h with Medium 199 supplemented with bovine serum albumin, heparin and antibiotics. A cannula was also inserted into the lumen. Light and scanning electron micrographs of control and perfused tubes showed that the epithelial lining was intact after perfusion. Tubal fluid was collected in 13 out of 19 experiments. Fluid could always be collected from patients who were in the follicular phase of their ovarian cycle. The mean rate of appearance was 48 microliters/h. The glucose, lactate and pyruvate concentrations in the tubal fluid, as assessed by fluorescence microanalysis, were 0.53, 8.58 and 0.17 mM respectively. There were no correlations between metabolite concentration and the length of perfusion, cannulation time, patient's age or condition. This technique provides a controlled method with which to access and examine human tubal fluid and will allow the physiology of both healthy and diseased tubes to be studied. PMID- 7782423 TI - The effect of pre-treatment with a gonadotrophin-releasing hormone agonist on reproductive functions in mature cycling rats. AB - In order to investigate the performance of follicles in a rat model in which gonadotrophin-releasing hormone agonist (GnRHa) was used for hypothalamic pituitary-ovarian axis suppression, three groups of mature cycling rats were studied. One group was treated with buserelin followed by pregnant mare's serum gonadotrophin (PMSG), and the second group was treated with PMSG alone. Both these hormonally treated groups received human chorionic gonadotropin for induction of ovulation. The third group received no hormonal treatment. The average number of ovulated oocytes recovered from rat oviducts pre-treated with GnRHa was significantly higher than that in rats treated with the gonadotrophin alone, in spite of the larger number of pre-ovulatory follicles present in the gonadotrophin-treated group. The morphology of both the pre-ovulatory and the post-ovulatory cumulus-oocyte complexes in the three groups appeared similar. No difference in the capacity of follicles of the three groups to synthesize progesterone in vitro in response to luteinizing hormone could be observed. We conclude that ovarian morphology and function are not impaired by pre-treatment with buserelin. PMID- 7782424 TI - Ultrasonographic appearance of polycystic ovaries is associated with exaggerated ovarian androgen and oestradiol responses to gonadotrophin-releasing hormone agonist in women undergoing assisted reproduction treatment. AB - While no single biochemical test is diagnostic of polycystic ovary syndrome (PCOS), most patients show a characteristic ovarian ultrasonographic appearance. It has been proposed that a dysfunction of cytochrome P-450c17 alpha in PCOS leads to an increased 17-hydroxyprogesterone (17-OHP) response to a gonadotrophin releasing hormone (GnRH) agonist-induced gonadotrophin rise. We postulated that this abnormality of steroid metabolism might influence the ovarian response during assisted reproduction treatment. We investigated 106 patients undergoing a short 'boost' stimulation regimen for assisted reproduction treatment, including in-vitro fertilization and gamete intra-Fallopian transfers. The ovarian ultrasound pattern was correlated with serum testosterone, 17-OHP, androstenedione and oestradiol responses, and with the clinical outcome. Polycystic ovaries, defined ultrasonographically as the presence of > or = 10 follicles between 2 and 10 mm diameter in either ovary, were found in 48% of the whole study population. Dexamethasone was given to suppress adrenal androgen secretion. Functional ovarian hyperandrogenism (FOH) was defined as serum testosterone > 0.5 nmol/l after dexamethasone. There was a significantly (P < 0.001) higher prevalence of FOH in patients with polycystic ovaries (23%) compared with normal ovaries (7%). Patients with polycystic ovaries had approximately double the 17-OHP, androstenedione and oestradiol responses to a GnRH agonist as patients with non-polycystic ovaries. Exaggerated 17-OHP and oestradiol responses to GnRH agonist were found in 89% of patients with clinically diagnosed PCOS. The number of oocytes retrieved was positively correlated (r = 0.51, P < 0.001) with the oestradiol responses in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782426 TI - Isolated polycystic morphology in ovum donors predicts response to ovarian stimulation. AB - The isolated finding of polycystic-appearing ovaries on ultrasound examination of normal women is not uncommon. The purpose of this study was to determine the clinical significance of polycystic ovaries in a population of healthy, non hirsute, fertile women preparing to undergo ovarian stimulation. We evaluated whether the finding of polycystic ovaries in oocyte donors predicts a different response to ovarian stimulation when compared to donors with normal-appearing ovaries. Furthermore, we examined whether oocytes from polycystic ovaries had the same capacity for fertilization and development as those retrieved from normal ovaries. In all, 11 donors with polycystic-appearing ovaries were compared prospectively to 13 donors with normal-appearing ovaries who were undergoing ovarian stimulation during the same time interval. The two groups were similar in age and baseline androgen concentrations. Significantly more oocytes were produced by the polycystic group for the amount of human menopausal gonadotrophin (HMG) administered (P < 0.05). In addition, all previous cycles completed by these 24 donors were compared (polycystic group: total of 31 cycles; normal group: total of 37 cycles). The donors with polycystic ovaries required less HMG to obtain optimal stimulation (P < 0.05), attained a greater peak oestradiol concentration (P < 0.05), produced a greater number of follicles (P < 0.05) and oocytes (P < 0.01) and a higher percentage of mature oocytes (P < 0.05). Furthermore, they achieved a higher peak oestradiol/HMG (P < 0.01) and oocytes/HMG ratio (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782427 TI - Sequential gonadotrophin-releasing hormone agonist/low-dose oral contraceptive treatment for leiomyomata uteri. AB - On the basis that gonadotrophin-releasing hormone agonists (GnRHa) induce a significant but transient shrinkage of leiomyomas and that oral contraceptive use may be associated with a decreased risk of fibroids, we tested the hypothesis that sequential GnRHa/low-dose oral contraceptive treatment could be a therapeutic alternative in perimenopausal women with uterine fibroids. Six premenopausal women with leiomyomata uteri were treated with D-tryptophan-6 luteinizing hormone-releasing hormone (D-Trp-6-LHRH) depot (Decapeptyl 3.75) for 6 months and demonstrated a significant reduction in mean uterine volume. A low dose oral contraceptive containing 30 micrograms of ethinyl oestradiol plus 150 micrograms of desogestrel was given during the ensuing 12 months. When GnRHa therapy was discontinued, there was a rapid regrowth of the uterine fibroids and the uterine volume had reached, or even exceeded, pretreatment values by the eighth to 12th month of contraceptive therapy. Sequential GnRHa/low-dose oral contraceptive treatment is not a useful tool for leiomyomata uteri. PMID- 7782425 TI - Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts. AB - Concerns have been raised recently about the possible association between superovulation and ovarian cancer. In order to contribute to the limited literature on this important issue, two cases of ovarian tumours in women who had undergone multiple ovulation inductions are presented. In the first case, the patient had secondary anovulatory infertility. She was treated with human menopausal gonadotrophin (HMG) alone and in combination with clomiphene citrate or buserelin for six cycles. She then underwent ovarian stimulation with buserelin/HMG in the long protocol for in-vitro fertilization (IVF) and embryo transfer. In preparation for a new IVF/embryo transfer attempt, 8 months later, the screening ultrasound revealed a cystic formation of the left ovary and an enlargement of the right. During laparotomy, both ovaries were found to bear large tumours (approximately 6 x 5 x 4 cm) which were removed. Histological examination showed that they were epithelial tumours (serous-papillary cystadenomas) of borderline malignancy. The patient conceived spontaneously 1.5 years after the operation. In the second case, the patient presented with secondary anovulatory infertility. She underwent ovulation induction with clomiphene/HMG and with buserelin/HMG in the long protocol, and intra-uterine insemination with husband's spermatozoa and conceived (singleton pregnancy). She was delivered by Caesarean section, during which a cystic tumour of the left ovary was removed. Histological examination revealed a benign mucous cystadenoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782428 TI - The influence of human chorionic gonadotrophin administration upon the next ovarian cycle. AB - We examined the influence of human chorionic gonadotrophin (HCG), used as an ovulation inducer and/or for supporting the luteal phase, on the next ovarian cycle. Four women received 10,000 IU of HCG at mid-cycle and another four received the same dose plus 1500 IU on the 17th, 19th and 21st days of the cycle. In the menstrual cycle prior to our experiments, venous blood samples were collected and vaginal ultrasound of the ovaries was performed every other day from day 21-28; the same data were also collected on days 1-10 of the experiment cycle. In such a way, control values were obtained. After the administration of HCG, venous blood samples were collected and ultrasound was performed in the same way and on the same days as in the controls. Follicle stimulating hormone (FSH) and luteinizing hormone were determined by radioimmunoassay in all blood samples, and HCG only in samples collected after the experiment. The results showed that only FSH was lower in the late luteal phase after the administration of 10,000 IU of HCG. Follicular diameters were higher during the follicular phase than during the previous cycle only in women who received the low dose of HCG. In addition, one woman presented with detectable HCG in the following ovarian cycle. The use of HCG in the preceding cycle may reduce FSH and develop persistent follicles in the subsequent cycle. We suggest that an ultrasound of the ovaries should be performed before starting a new ovulation induction cycle in a woman who has received HCG in the previous cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782430 TI - Identification of human sperm surface glycoproteins by sperm membrane-specific autoantibodies. AB - In order to identify the surface antigens of human spermatozoa recognized by the sera of immune infertile men, sperm membrane-specific antibodies were obtained from three serum samples exhibiting high titres of antibodies with different sperm-binding patterns. Serum antibodies were adsorbed onto normal motile spermatozoa and subsequently eluted from the sperm membrane. Using the immunoblotting technique under renaturating conditions, the sperm-eluted antibodies were tested against an electrophoretically fractionated sperm membrane preparation. A total of 15 protein bands ranging from 110 to 16 kDa were defined, but the immunoblot profiles differed quantitatively and qualitatively from one serum to another. Only two polypeptides were recognized by the three sperm membrane-specific antibody preparations; one of 90 kDa and another of 110 kDa. Blots were also used for the affinodetection of specific oligosaccharide side chains. Three lectins were tested (concanavalin A, Pisum sativum, and wheat germ agglutinin). Of the 15 protein zones recognized by the antibodies, 11 bound at least one lectin and should contain glycopeptides with oligosaccharides of four different types: N-linked biantennary complex type, N-linked fucosylated complex type, N-linked lactosaminyl complex type with terminal sialic acid and polysialyl type oligosaccharides. Further analysis of these glycoproteins will be pursued with sperm-associated antibodies eluted from the ejaculates of infertile men in order to define those with a potential role in the fertilization process. PMID- 7782429 TI - Ovarian response in consecutive cycles of ovarian stimulation in normally ovulating women. AB - Ovarian stimulation combined with intra-uterine insemination (IUI) is an effective treatment of non-tubal infertility but most women undergo several cycles of treatment to achieve a pregnancy. This prospective study was designed to assess the consistency (or variation) of ovarian responses and the effect of various ovarian stimulation protocols on this consistency in consecutive cycles of ovarian stimulation and IUI in women with non-ovulatory infertility. A total of 86 regularly menstruating ovulating patients each completed three to six cycles of ovarian stimulation and IUI (n = 347 cycles). Ovarian stimulation was achieved by sequential clomiphene citrate/human menopausal gonadotrophin (HMG), HMG-only or combined gonadotrophin-releasing hormone analogue--HMG protocols in 33, 29 and 24 patients respectively, and each patient used the same protocol consistently throughout the study. Standard methods were used to monitor ovarian response and to perform IUI. Using each patient as her own control, repeated measurements analysis of variance revealed consistency of ovarian response in consecutive ovarian stimulation cycles, as shown by the number and mean diameter of maturing pre-ovulatory follicles, peak plasma oestradiol, duration of stimulation and mean HMG requirements. This consistency existed using any of the ovarian stimulation protocols. We conclude that regularly menstruating and ovulating women are likely to have similar ovarian responses in consecutive cycles of ovarian stimulation and IUI if the same ovarian stimulation protocol is used consistently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782431 TI - Anti-endometrial lymphocytotoxicity and natural killer cell activity in baboons (Papio anubis and Papio cynocephalus) with endometriosis. AB - This study was performed to test the hypothesis that anti-endometrial, lymphocyte mediated cytotoxicity and natural killer (NK) activity are reduced in baboons with endometriosis when compared to animals with a normal pelvis. Lymphocyte mediated cytotoxicity was determined in 28 baboons (15 with endometriosis, 13 with normal pelvis) and NK cell activity was evaluated in 42 baboons (31 with endometriosis, 11 with normal pelvis). Anti-endometrial lymphocyte-mediated cytotoxicity was determined by a 20 h assay with effector-target ratios of 50:1 and 25:1. The NK activity (K562 cell line as target) was simultaneously measured in all animals during a 4 h assay with effector:target ratios of 200:1, 100:1, 50:1, 25:1, 12:1, 6:1 and 3:1. Statistical analysis was performed using analysis of variance, paired rank, Mann-Whitney, Kruskal-Wallis and Fisher exact tests where appropriate. Lymphocyte-mediated cytotoxicity was significantly lower (P < 0.025) in baboons with endometriosis (mean 5.9 +/- 8.7%, median 0%, range 0-26%) than in animals with a normal pelvis (mean 22.9 +/- 23.0%, median 7%, range 0 78%). This difference could be explained by the absence of cytotoxicity in baboons with moderate to severe endometriosis, probably due to high spontaneous release of 51Cr from labelled target cells. When stricter criteria were used and only animals with a labelling index (maximal/spontaneous release) of > or = 1.7 were analysed (n = 11), the anti-endometrial cytotoxicity was comparable between baboons with and without endometriosis. NK cell activity was also comparable in primates with and without endometriosis. In conclusion, no difference in lymphocyte-mediated cytotoxicity and NK cell activity was observed between baboons with and without endometriosis. PMID- 7782432 TI - Results of decentralized in-vitro fertilization treatment with transport and satellite clinics. AB - The results of in-vitro fertilization (IVF) treatments carried out in a university IVF centre are compared with those obtained following 15-40 min transportation of oocytes from a transport IVF clinic to the central IVF laboratory of the university centre. Moreover, treatment results following monitoring of ovarian stimulation in satellite clinics, combined with ovum retrieval at the transport clinic and transport of oocytes to the central IVF laboratory, are described. In a total of 5540 IVF treatment cycles, 24-26% of viable pregnancies per embryo transfer were found in the three groups. Comparison of results, obtained with the three different treatment modalities, showed no negative influences of transporting oocytes from transport clinic to IVF laboratory and of monitoring ovarian stimulation in satellite clinics. It is concluded that decentralization of the clinical phase of IVF treatment is possible. This leads to a more optimal use of existing laboratory facilities in large urban areas. It is stressed that good communication between satellite clinic, transport clinic and IVF laboratory is necessary for a decentralized IVF programme. To obtain good quality assurance, both the satellite clinic and the transport clinic must adhere to the same protocol. PMID- 7782433 TI - Semi-programmed ovarian stimulation as the first choice in in-vitro fertilization programmes. AB - The objective of this work was to evaluate the results obtained with a protocol of semi-programmed ovarian stimulation (low-dose contraceptive pill+clomiphene citrate+human menopausal gonadotrophin+dexamethasone) used as the first-choice method for in-vitro fertilization (IVF). A total of 207 punctures was performed for oocyte collection from 168 patients (mean age 31.0 +/- 4.0 years); mean infertility duration was 5.81 +/- 3.30 years. The infertility factors indicating IVF for this population were as follows: tubo-peritoneal factor, 68%; pure or associated male factor, 9.2%; endometriosis, 11.1%; ovulatory factor, 4.3%; idiopathic factor, 11.6%; others, 2.4%. No oocyte was found on aspiration in five procedures (2.4%), with the mean number of oocytes collected per cycle being 5.87 +/- 3.3 (range 0-18). The cancellation rate per puncture was 5%. The mean embryo cleavage rate was 60.2 +/- 36.8%, with transfer of at least one embryo occurring in 82.6% of all punctures. The mean number of transferred embryos was 2.52 +/- 1.60 (range 1-5). The clinical pregnancy rates per started cycle and per puncture were 22.4 (218 ovarian stimulation cycles) and 23.6% (a total of 49 clinical pregnancies, 36 single, nine twins and four triplets) respectively. The clinical pregnancy rate per embryo transfer was 28.6%. The embryo implantation rate was 12.6%. The abortion rate was 16.3%. The index of deliveries per puncture was 19.8%. There were no cases of moderate or severe ovarian hyperstimulation syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782434 TI - In-vitro fertilization in completely natural cycles. AB - Our objective was to assess the efficacy of in-vitro fertilization (IVF) in natural ovarian cycles in couples with tubal and unexplained infertility. A prospective study design was used. A total of 39 fully investigated couples, who were patients at the Reproductive Medicine Unit, St Michael's Hospital, Bristol, UK, took part; they were diagnosed with either tubal disease (n = 26) or unexplained infertility (n = 13). Procedures involved daily capillary blood sampling, daily vaginal ultrasonography and vaginal oocyte recovery under sedation at mid-cycle. The main outcome measures were fertilization, implantation and pregnancy rates. Although more of the women with tubal disease were parous, there were no other significant differences between the two groups. The 39 couples with infertility of tubal or unexplained aetiology had 79 cycles of IVF in otherwise completely natural cycles. The overall fertilization rate was 80% and the implantation rate was 14.0%. A trend was observed for higher success rates in women with tubal disease. We conclude that natural cycle IVF and embryo transfer offers an acceptable chance of pregnancy and an opportunity for the in depth investigation of follicular and ovarian function in couples with defined causes of infertility. The possibly lower success rate in women with unexplained infertility warrants further study of follicular function and endocrinology. PMID- 7782435 TI - Hydrosalpinges in in-vitro fertilization: an unfavourable prognostic feature. AB - The aim of this study was to determine whether the presence of a hydrosalpinx influences in-vitro fertilization (IVF) prognosis. Comparisons were made between 69 IVF cycles in 37 patients carrying hydrosalpinges (hydrosalpinx group) and 67 IVF cycles in 41 patients without tubes or surgically sterilized (control group). Twenty-two patients carrying hydrosalpinges underwent salpingectomy or salpingoplasty (operated group); they then underwent 42 IVF trials which were compared with the two former groups. In the hydrosalpinx group, pregnancy rates by oocyte retrieval were 10.1% for clinical and ongoing pregnancies. In the control group, the corresponding pregnancy rates were 23.0 and 21.3% respectively. The implantation rate per embryo was 4.2% for clinical and ongoing pregnancies in the hydrosalpinx group and 11.0 and 10.4% respectively in the control group. The operated group had pregnancy rates of 38.1% for clinical pregnancies and 31.0% for ongoing pregnancies, with implantation rates of 17.4 (clinical) and 14.8% (ongoing) respectively. Pregnancy and implantation rates were statistically lower in the hydrosalpinx group as compared with controls and with the operated group. The differences between control and operated groups were not significant. In conclusion, the presence of a hydrosalpinx is thus associated with poor prognosis in IVF treatment. Surgical correction of such lesions appears to restore high success rates. PMID- 7782436 TI - The predictive value of computer-assisted semen analysis in the context of a donor insemination programme. AB - In this paper we examine the value of both conventional and computer-assisted semen analysis (CASA) using the Hamilton-Thorn HTM-S 2030 in predicting the in vivo fertility of cryopreserved donor semen. Semen samples were examined prospectively and data on the conventional criteria of semen quality, sperm morphometry and movement were collected. Of 61 ejaculates identified, 33 achieved pregnancies ('successful') and 28 failed to do so ('unsuccessful'), despite insemination into at least four different normal female recipients. When the post thaw semen profiles were compared, no differences were observed between the two groups in respect of the conventional criteria of semen quality determined by conventional laboratory techniques; however, there were differences in respect of both morphometry and movement characteristics determined by the HTM-S. When multiple logistic regression was used to examine the ability of the variables measured to predict the achievement of pregnancy, the conventional criteria of semen quality were of no value (chi 2 = 6.67, P = 0.353). However, the CASA assessment successfully predicted outcome in 86.9% of cases (chi 2 = 44.3, P = 0.0021). It was concluded that CASA assessment is of significant value in predicting the ability of an ejaculate to achieve pregnancy. PMID- 7782437 TI - Clinical value of sperm morphology for in-vivo fertility: comparison between World Health Organization criteria of 1987 and 1992. AB - The World Health Organization (WHO, 1992) has suggested new criteria for scoring sperm morphology. This study compares the clinical value of the new criteria, i.e. classification of a man as fertile or infertile, to those previously established by the WHO (1987). Papanicolaou-stained semen smears from 166 men attending our infertility clinic, whose fertility status was known, were scored using both methods. Using logistic discriminant analysis for compositional data, no difference between these two sets of criteria with respect to predicting pregnancy outcome was observed. The categorization of the abnormalities (head, midpiece, tail) provides no extra clarification. The WHO (1992) cut-off point of 30% for normal forms is not appropriate, as approximately half of the men in the fertile group had a normal sperm morphology below this limit. In conclusion, the present WHO (1992) classification of sperm morphology is of no additional clinical value. Studies on sperm morphology should concentrate on obtaining biological data on, and measurements of, spermatozoa which are functionally active. Only then can the definition of normal be achieved and clinically useful criteria be adopted. PMID- 7782438 TI - Nuclear decondensation of sperm head and failure at in-vitro fertilization: an ultrastructural study. AB - The problem of unexplained male infertility was investigated by electron microscopic study of spermatozoa from 51 males. The subjects were subdivided as follows: group A (n = 25) normal fertile males (controls), group B (n = 13) successful in-vitro fertilization (IVF) cases (fertilization rate > 50%), group C (n = 13) failed IVF cases. All subjects included in groups B and C had a 6-12 year history of childlessness and IVF was employed when other methods of assisted reproduction failed. The study of spermatozoa in fertile males (controls) was carried out to establish baseline ultrastructural abnormalities. In all 51 cases, an average of 330 (280-800) sperm heads and 660 (330-1190) sperm tails were studied. Decondensation of nuclear chromatin was observed in 70 +/- 15% (mean +/- SD) of spermatozoa in failed IVF cases, 16 +/- 5% in successful IVF cases and 7 +/- 3% in controls. These results were found to be statistically significant (P > 0.001). The mean value for motility of spermatozoa in all three groups was within accepted limits of normality. It is concluded that decondensation of nuclear chromatin seen by electron microscopy is one of the most important causes of male infertility. It is advocated that electron microscopic examination of semen should be carried out in all cases of long-standing, unexplained male infertility before embarking upon IVF programmes. PMID- 7782439 TI - Pregnancy following discontinuation of a calcium channel blocker in the male partner. AB - The fertility potential of human sperm populations can be assessed by the presence of head-directed mannose ligand receptors (mannose-specific lectin) and the occurrence of spontaneous acrosome reactions after incubation under capacitating conditions in vitro. We have reported previously on the interaction between anti-hypertensive medications and their effects on these parameters of male fertility potential. In this report we document the effects of cessation of calcium ion channel blocker medication on male fertility. Motile spermatozoa from a 30 year old infertile patient on a calcium ion channel blocker as anti hypertensive treatment had subnormal expression of mannose-specific lectin and did not exhibit spontaneous acrosome reactions. Three months following discontinuation of the medications, complete recovery of both the expression of head-directed mannose ligand receptors and the acrosome reaction was documented, though sperm motility and morphology remained unchanged. The couple had 2 years of infertility and previously failed to conceive through seven cycles of Pergonal/intra-uterine insemination. Conception occurred on the second Pergonal/intra-uterine insemination cycle after the husband discontinued calcium ion channel blocker medication. Calcium ion channel blockers may adversely affect sperm fertilizing potential. Discontinuation of such medications enhances the changes for conception. PMID- 7782440 TI - Density adjustment of software settings minimizes bias in automated sperm motility estimation. AB - To minimize overestimation of motility, it is recommended that fresh semen be diluted with seminal plasma prior to automated analysis. However, for glycerolated or cryopreserved semen this is impractical, and alternative methods are needed to minimize automated motility bias. In the present study, the proportion of motile spermatozoa was determined in fresh, diluted and cryopreserved semen (n = 25 ejaculates) using visual and automated methods. The effect of software settings on motility was investigated by assessing samples at a range of modified settings. At standard settings, automated motility was biased in fresh semen (+7.2%) after dilution with cryopreservative (-2.9%) and after cryopreservation (-7.8%) (P < 0.0001 versus visual). Automated motility was inversely related to the minimum number of frames for motility sampling (P < 0.0001), with mean estimates of 41.0, 46.1, 52.0 and 58.2% generated at settings of 8, 4, 2 and 1 frame(s) respectively (n = 15 fresh, diluted and cryopreserved samples). Based on an arbitrary ordinal scale, a method was developed whereby motility sampling was adjusted prior to analysis according to sperm density. Analysis of an independent set of semen samples with density-adjusted software settings reduced bias in automated estimates (n = 30) before and after freezing (P < 0.0001). In addition, bias was no longer related to sperm density. In conclusion, modification of software settings is an effective alternative to dilution to minimize bias in automated motility estimates in fresh, diluted and cryopreserved human semen. PMID- 7782441 TI - Clinical and biological characteristics of infertile men with a history of cryptorchidism. AB - Out of 85 fertile and 1014 infertile men, two (2.4%) and 95 (9.4%) respectively had a history of cryptorchidism. Thus cryptorchidism appears to be a risk factor for fertility since this difference was significant. Further comparisons showed that the volume of a former cryptorchid testis was smaller than the contralateral normally descended one and that sperm output/concentration was more impaired in bilateral than in unilateral cryptorchidism. A retractile testis, defined as a testis reported by the patient to be spontaneously and regularly, i.e. at least once a week, ascending up into a supra-scrotal position, was more frequent in infertile men with a history of cryptorchidism than in fertile men. Retractility was more frequent on the cryptorchid side, and was found more frequently after hormonal than after surgical treatment. Independently of all epidemiological and clinical parameters studied, retractility was associated with a lower sperm output. Among the infertile men with a history of cryptorchidism, 45% had an abnormally high scrotal temperature. This abnormal temperature represented a pejorative risk factor for fertility in this group, since it was associated with a more severely impaired spermatogenesis and a higher incidence of primary infertility than in infertile men with a history of cryptorchidism but normal scrotal temperatures. PMID- 7782442 TI - External quality assessment for semen analysis and sperm antibody detection: results of a pilot scheme. AB - The need for quality assurance in the seminology laboratory is clear, as the techniques of semen analysis and sperm antibody detection are just as susceptible to variation as any other routine pathology test. Semen samples were distributed to 20 laboratories on six occasions, four samples per distribution, for sperm concentration and morphology assessment under routine conditions, together with an equal number of serum samples for sperm antibody detection. The semen analysis results showed a wide range of values for any given sample, which did not seem to be related to the methodology used. However, this variation appears to be related to the presence of persistent errors, as most laboratories showed reasonable between-assay and within-assay variation. Detection of sperm antibodies by the tray agglutination, gelatin agglutination or indirect immunobead test showed a consistent discrimination between the intended positive and intended negative samples. However, the use of fluorescent microscopy was unable to do this. This study has shown the feasibility of operating external quality assessment schemes for semen analysis and sperm antibody detection. These schemes provide the opportunity for individual laboratories to fully evaluate their own methods against those of others and to determine the stages at which any errors occur. An increased number of participants will ultimately enable a systematic comparison of different methods. PMID- 7782443 TI - Successful fertilization and establishment of pregnancies after intracytoplasmic sperm injection in patients with globozoospermia. AB - Globozoospermia or round-headed spermatozoa is a rare type of teratozoospermia where the acrosome is absent resulting in male infertility with no known therapy. A few studies have shown that round-headed spermatozoa cannot bind to or penetrate the zona pellucida, and no normal fertilization has been observed in in vitro fertilization (IVF) after insemination of human oocytes with round-headed spermatozoa. In this study, the fertilization capacity of round-headed spermatozoa after intracytoplasmic sperm injection (ICSI) into human oocytes has been examined. In pre-clinical experiments, 45 oocytes were injected; 41 oocytes were intact after injection, 15 oocytes were fertilized normally, and 13 of these 15 oocytes developed further in vitro. ICSI was carried out in 11 treatment cycles of seven infertile couples with globozoospermia. Normal fertilization and embryo transfer occurred in four cycles (three patients). Positive serum human chorionic gonadotrophin was observed in three cycles (two patients); one patient had a pre-clinical abortion and the other patient became pregnant twice; the first pregnancy was ectopic and the second pregnancy is a twin pregnancy which is currently at 16 weeks of gestation. PMID- 7782444 TI - Rectovaginal septum, endometriosis or adenomyosis: laparoscopic management in a series of 231 patients. AB - A series of 231 cases of deep-infiltrating endometriosis of the rectovaginal septum is presented. Laparoscopic procedures with excision of deep fibrotic endometriotic nodules were performed in all cases. In three cases, the bowel lumen was entered. No other peri-operative complications were observed. Three cases of urinary retention were reported. The nodule resection resulted in considerable pain relief. Histologically, the rectovaginal nodule was similar to an adenomyoma. Indeed it was a circumscribed nodular aggregate of smooth muscle and endometrial glands. This form of disease must be considered as a specific disease which originates from the Mullerian rests present in the rectovaginal septum and we suggest that it be called 'rectovaginal adenomyosis'. PMID- 7782445 TI - Can Matrigel substitute for Vero cells in promoting the in-vitro development of mouse embryos? AB - The influences of Vero cells and the basement membrane substratum for these cells (Matrigel) on the rate of hatched blastocyst formation from mouse zygotes in vitro were compared. Zygotes obtained from C57BL/6 x BALB/c F1 females pretreated with pregnant mare's serum gonadotrophin/human chorionic gonadotrophin mated with BDF1 males were cultured (120 h) in human tubal fluid medium supplemented 0.5% with bovine serum albumin. The rates of early hatching and hatched blastocyst formation at 96 and 120 h of culture were expressed as the percentage of 2-cell embryos visualized after the initial 24 h. The rate of total blastocyst formation did not differ between treatment groups. However, < 10% of embryos cultured for 96 h in medium alone advanced to the hatching stage compared with 35-40% of blastocysts cultured with Vero cells or with Matrigel alone. Similarly, by 120 h of culture, only 20% of embryos cultured in medium alone developed to hatching or hatched blastocysts compared with > 70% for those embryos co-cultured with Vero cells or with Matrigel. In conclusion, Vero cells improved the rate of development of mouse embryos to hatched blastocysts during serum-free culture. Similar improvements were seen in the presence of Matrigel alone; Matrigel is the basement membrane substratum used for the Vero cells. Further studies on the means whereby Matrigel promotes early embryonic development (e.g. appropriate combination of basement membrane-associated growth factors) may lead to a safe, defined medium preparation for the stimulation of in-vitro development of human embryos. PMID- 7782446 TI - Timing of pronuclear development and first cleavages in human embryos after subzonal insemination: influence of sperm phenotype. AB - The sequential transformations of human sperm nuclei in human eggs after subzonal insemination (SUZI; n = 104) and the influence of sperm defects on this timing were studied. This chronology was compared to that of two control series of zygotes obtained after SUZI with normal spermatozoa (n = 35) and after in-vitro fertilization (IVF) with normal donor spermatozoa (D-IVF; n = 220). Pronuclear formation took place between 4.5 and 10.5 h post-SUZI for 92.8% of the zygotes. They remained visible for 13 h and began to disappear 18.5 h post-SUZI. The timespan 3 h. Zygotes obtained after D-IVF had a similar rate of pronuclear disappearance but approximately 4 h later. The second cell cycle was more rapid for zygotes obtained by D-IVF than by SUZI, but the developmental rate of zygotes obtained by SUZI varied according to sperm phenotypes. For patients with previous unexplained IVF failures (control group with normal spermatozoa), the developmental rate was lower, suggesting the influence of oocyte quality. In conclusion, the end of the first cell cycle of zygotes obtained by insemination under the zona pellucida appears 4 h earlier compared to zygotes obtained after insemination outside the zona pellucida. PMID- 7782447 TI - Synthetic and biological macromolecules: protection of mouse embryos during cryopreservation by vitrification. AB - The ability of macromolecules to protect 8-cell mouse embryos during a vitrification protocol was assessed by the comparison of a synthetic macromolecule, polyvinylpyrrolidone (in the form of Percoll), and a biological macromolecule, human serum albumin (HSA). Vitrification solutions, which included glycerol (50% v/v), sucrose (0.75 mol/l) and either macromolecule Percoll (50% v/v) or HSA (1.125% w/v), were found to provide similar rates of survival. Both compounds resulted in a significant reduction in the incidence of disruption to the zonae pellucidae of cryopreserved embryos, to 4.8 +/- 1.3% and 10.3 +/- 1.2% respectively, when compared to the outcome when neither was present in the vitrification solution (20.4 +/- 2.5%; P < 0.01). Polyvinylpyrrolidone in the form of Percoll offers advantages over HSA in this work: it provides a lower rate of zona disruption and avoids the need for screening for pathogenic contaminants such as human immunodeficiency virus and hepatitis B and C. PMID- 7782448 TI - Parthenogenetic activation of human oocytes following cryopreservation using 1,2 propanediol. AB - Fresh and aged human oocytes were cryopreserved using 1,2-propanediol (PROH). After thawing, the oocytes were cultured for 20 h and examined for parthenogenetic activation using light microscopy and an ultraviolet DNA stain. Control fresh or aged oocytes and oocytes exposed to PROH without cryoperservation were also examined for activation. No control oocytes were observed to activate spontaneously (n = 43) and parthenogenetic activation was not induced by exposure to PROH alone (n = 26). In both fresh and aged cryopreserved oocytes, 27 and 29% of the oocytes respectively were activated, and these proportions were significantly elevated compared with the controls (P < 0.01). Although a similar rate of activation was observed for the cryopreserved fresh and aged oocytes, the form of parthenogenetic activation varied between these two types of oocyte. A single pronucleus was observed in 18% of the fresh and 5% of the aged cryopreserved oocytes. In contrast, the presence of two or more pronuclei was observed in 0% of the fresh and 19% of the aged cryopreserved oocytes. PMID- 7782449 TI - A comparison of the effects of different biopsy strategies on the post-thaw survival of 8-cell-stage mouse embryos: implications for preimplantation diagnosis. AB - The aim of this study was to investigate the effects of two different biopsy strategies, zona slitting and zona piercing, on the post-thaw survival and subsequent in-vitro development of 8-cell mouse embryos. From control experiments it was determined that neither biopsy by zona slitting nor zona piercing adversely affected embryo development in vitro, as similar rates of blastocyst formation and hatching were found between biopsied and zona-intact embryos; there was, however, a trend towards a lower rate of blastocyst hatching in embryos biopsied by zona piercing (78.3% compared with 91.9% of zona-intact embryos). When biopsy was followed by cryopreservation a different picture was seen: similar rates of freeze-thaw survival were found for zona-slit, zona-pierced and zona-intact embryos (84.2, 88.5 and 87.2% respectively), but this was superseded by a significant (P < 0.05) reduction in the blastocyst formation rates (61.4% zona-slit and 63.9% zona-pierced versus 78.7% zona-intact) and hatching rates (51% zona-slit and 52.5% zona-pierced versus 72.3% zona-intact) of the biopsied embryos. When the effects of zona slitting and piercing were considered in isolation, i.e. without performing biopsy, it was found that the larger holes produced by zona slitting rendered embryos more susceptible to freeze-thaw damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782450 TI - First trimester embryo reduction: a medical solution to an iatrogenic problem. AB - The incidence of multiple pregnancies is increasing, mainly as a consequence of the widespread use of various infertility protocols. Since such gestations present a high risk of feto-maternal morbidity and mortality, selective first trimester fetocide remains one of the few reasonable options. We reviewed the literature dealing with the outcome of 804 multiple pregnancies following the use of transcervical, transvaginal or transabdominal approaches. Questions relating to dealing with technical failure, method of fetocide and procedural improvements are examined. In a comparison of the variables: miscarriage, preterm delivery, perinatal and neonatal loss rates, the transvaginal approach fares better, but statistical significance (P < 0.001) is achieved only for preterm delivery. We speculated that this might be attributable to the very early gestational age at which the procedure is usually performed. However, the transabdominal approach offers better results when post-manipulation maternal morbidity is considered, i.e. infection and vaginal bleeding. Since each option offers different advantages and disadvantages, additional experience and larger population samples are required to further clarify this important issue. PMID- 7782451 TI - A challenge to the concept of tubal reflux to explain the rise and fall of CA125 in serum during the first trimester. AB - Although amniotic fluid concentrations of cancer antigen (CA) 125 rise during the first two trimesters of pregnancy, the serum concentrations of CA125 peak during the first trimester and drop to non-pregnant values in the second and third trimester. A previous hypothesis to explain this phenomenon was that in the early first trimester decidual CA125 gains access to the maternal compartment via 'tubal reflux' and subsequent absorption by peritoneal lymphatics. However, as pregnancy advances, the decidua capsularis fuses with the decidua parietalis, thus obliterating the endometrial cavity at 10-12 weeks; the Fallopian tubes thus become functionally obstructed. To test this hypothesis, we evaluated early first trimester CA125 concentrations in women conceiving by in-vitro fertilization (IVF) and embryo transfer with patent tubes (group 1) and in those conceiving by IVF and embryo transfer with bilateral tubal occlusion (group 2). We also compared those conceiving with human menopausal gonadotrophin therapy for ovulation induction without assisted reproduction (group 3) and those conceiving without fertility drugs in assisted reproduction (group 4). Mean CA125 concentrations were similar in groups 1-3; the mean CA125 concentration in group 4 was lower but this difference was not statistically significant, probably due to the small sample size. These data do not support the concept that tubal reflux explains the rise and fall of serum concentrations of CA125, since these were equal in IVF conceptions with or without tubal patency. PMID- 7782452 TI - Testosterone and androstenedione in premature ovarian failure pregnancies: evidence for an ovarian source of androgens in early pregnancy. AB - Numerous anecdotal reports but few scientific approaches have suggested an increase in androgens in early pregnancy. In this study we have compared the concentration of serum androgens, testosterone and androstenedione in early pregnancy, starting within the cycle of conception. We have taken the opportunity to study women with premature ovarian failure where pregnancy develops in the virtual absence of ovarian functions. This study demonstrates that the concentration of testosterone (0.29 +/- 0.04 ng/ml) and androstenedione (1.770 +/ 0.136 ng/ml) in these subjects is as low as, if not lower than, non-pregnant women (0.39 +/- 0.02 and 2.170 +/- 0.025 ng/ml), significantly increased in normal pregnancies (1.190 +/- 0.118 and 3.920 +/- 0.297 ng/ml; P < 0.05) and even further increased in human menopausal gonadotrophin-treated cycles (1.990 +/- 0.230 and 8.19 +/- 0.72 ng/ml; P < 0.05). These studies demonstrate that the ovary is a contributor to the circulating concentrations of testosterone and androstenedione starting within the cycle of conception. PMID- 7782453 TI - Heterotopic abdominal pregnancy following in-vitro fertilization/embryo transfer presenting as massive lower gastrointestinal bleeding. AB - We present a case that, as far as we know, is the first report of lower gastrointestinal haemorrhage as a complication of heterotopic pregnancy induced by artificial reproductive technology. The heterotopic abdominal pregnancy caused erosion of the intestinal wall and massive rectal bleeding, 8 weeks after in vitro fertilization/embryo transfer. The source of the bleeding could not be identified despite comprehensive investigation including gastroscopy, ultrasonography, sigmoidoscopy, 99Tc (technetium) scanning and angiography. Tagged-erythrocyte isotope scanning revealed an abnormal concentration in the left lower quadrant, compatible with active bleeding in the area of the terminal ileum. Laparotomy disclosed a heterotopic abdominal pregnancy, causing erosion of the intestinal wall at this site. As assisted reproductive technologies become more and more common this rare complication of intestinal erosion should be kept in mind in case of lower gastrointestinal bleeding. PMID- 7782454 TI - Clearance curves of serum human chorionic gonadotrophin for the diagnosis of persistent trophoblast. AB - A well recognized hazard of conservative surgical treatment of tubal pregnancy is incomplete removal of trophoblastic tissue. Persistent trophoblast can be detected by postoperative serum human chorionic gonadotrophin (HCG) monitoring. The impact of various surgical techniques on the post-operative clearance of serum HCG was investigated in a retrospective study. The medical records of 97 patients treated surgically for tubal pregnancy in the Academic Medical Center of the University of Amsterdam, The Netherlands, between 1 January 1992 and 1 August 1994 were reviewed; 28 patients were treated by salpingostomy by laparoscopy, 16 by salpingostomy by open surgery and 53 by salpingectomy by either method. There was no difference in the post-operative clearance of serum HCG after successful conservative surgery compared to radical surgery. However, persistent trophoblast occurred in eight patients (29%) after laparoscopic salpingostomy and in only one patient (6.3%) who had a salpingostomy by open surgery (relative risk 4.57). Serum HCG clearance curves allow early identification of patients with persistent trophoblast after conservative surgical treatment. Moreover, monitoring of post operative serum HCG until it becomes undetectable is mandatory in order to reveal late-onset types of persistent trophoblast. PMID- 7782455 TI - Blood flow changes in uterine and ovarian vasculature, and predictive value of transvaginal pulsed colour Doppler ultrasonography in an in-vitro fertilization programme. AB - The role of transvaginal pulsed colour Doppler ultrasound in the prediction of the outcome of in-vitro fertilization (IVF) therapy was assessed longitudinally in 30 patients during stimulated cycles. The pulsatility index (PI) of the uterine arteries did not change significantly until the mid-luteal phase. Within 6 days after the beginning of stimulation the maximum peak systolic velocity of the uterine blood flow had increased significantly from 27.6 +/- 8.9 to 36 +/- 12.8 cm/s. No difference was found in uterine PI between pregnant and non pregnant women. The PI of intra-ovarian flow was also similar in both groups. However, there was an insignificant increase in uterine receptivity when the PI of the uterine artery was between 2.0 and 2.99 on the day of embryo transfer. Nevertheless, the appraisal of the prognostic outcome of the treatment could not be made with Doppler. PMID- 7782457 TI - Progesterone receptors on lymphocytes. PMID- 7782456 TI - Investigation of recurrent miscarriage. PMID- 7782458 TI - Endometrial oestrogen and progesterone receptors and their relationship to sonographic endometrial appearance. AB - The present study was undertaken to evaluate a possible relationship between the endometrial concentrations of oestrogen receptor (ER) or progesterone receptor (PR), and the sonographic appearance of human endometrium. Sonographic assessments and aspirations of the endometrium at the time of or prior to ovulation were made in 48 cycles of 45 infertile women. Endometrial patterns were classified as A, triple line pattern, or B, not triple line, on the basis of echogenicity. We did not find a correlation between ER or PR and serum oestradiol or endometrial thickness. Furthermore, serum oestradiol concentrations were not correlated with endometrial pattern or thickness. The only significant correlations were found between the concentrations of ER and PR in the pattern A endometrium (r = 0.80, P < 0.01) and in the pattern B endometrium (r = 0.49, P < 0.05). There were no differences in the mean concentrations of ER and PR despite differences in endometrial pattern and thickness. However, PR was measured at > 800 fmol/mg protein in 12 out of 38 pattern A endometria, while PR was < 800 fmol/mg protein in all pattern B endometria. These data suggest that high PR expression in the pre-ovulatory period is related to an adequate endometrial growth and thereby increases the responsiveness of the endometrium to progesterone stimulation after ovulation. PMID- 7782459 TI - Roles of growth factors during peri-implantation development. AB - Several growth factor ligand and receptor gene products have been shown to play roles during preimplantation mammalian development. Genes for insulin-like growth factors (IGFs), transforming growth factors (TGFs), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and receptors for insulin, IGF, PDGF, TGF alpha and epidermal growth factor (EGF) are expressed by early embryos of several species including mouse, rat, cow and sheep. Roles of growth factors during early development have been demonstrated by addition of purified growth factors to culture medium or by molecular genetic techniques that interfere with gene expression. In this way, it has been shown that successful development of the blastocyst is dependent on the action of epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Recent experiments show that both LIF and EGF stimulate secretion of urokinase-type plasminogen activator (uPA) and gelatinase B/matrix metalloproteinase-9 (MMP-9) in day 7 mouse blastocyst outgrowths. At the same time, tissue inhibitors of MMPs (TIMPs) are also expressed by embryonic, decidual and uterine tissues during the implantation process. It appears that LIF may act directly or indirectly, by inducing the expression of other cytokines, to regulate the temporal and spatial production and activity of proteases and protease inhibitors to create a favourable environment for implantation. PMID- 7782460 TI - Gelatinase and oncofetal fibronectin secretion is dependent on integrin expression on human cytotrophoblasts. AB - Collagenolytic activity of cytotrophoblasts is stimulated by glycoproteins of the extracellular matrix and since this stimulation can possibly occur through integrins, we measured the gelatinolytic activity of villous and extravillous cytotrophoblasts according to the type of integrins expressed on these cells. Cytotrophoblasts were isolated from legal abortions, immunopurified with anti CD45, separated according to their expression of histocompatibility-linked antigen (HLA)-G, alpha 6 or alpha 5 integrin subunits and cultured for 5 days on plastic or agarose. Fetal fibronectin, human chorionic gonadotrophin (HCG) and the gelatinolytic activity were measured in the culture supernatants. Following immunopurification with anti-CD45, the gelatinolytic activity of cytotrophoblasts was significantly higher than before, indicating that contaminating lymphomyeloid cells secreted gelatinolytic inhibitors. HLA-G positive cells secreted significantly more gelatinases than HLA-G negative cells but their HCG secretion was similar. Compared to alpha 5 positive cells, alpha 6 positive cytotrophoblasts secreted significantly more gelatinases, significantly less fibronectin but similar amounts of HCG. We conclude that during trophoblast invasion, extravillous cytotrophoblasts (HLA-G positive) expressing the alpha 6 integrin subunit represent the invasive population of cells (high gelatinase and low fibronectin secretion). When expression of the alpha 5 integrin subunit is turned on, their invasive behaviour ceases and they secrete low amounts of gelatinases and high concentrations of fibronectin. PMID- 7782461 TI - Multiplex polymerase chain reaction for sex determination of single mouse blastomeres. AB - Using a multiplex nested polymerase chain reaction (PCR) method with single copy genes and a dinucleotide repeat locus for the mouse Y and X chromosomes respectively, it was possible to discriminate between single cells derived from male and female embryos. Using single cells, amplification of Sry and Zfy sequences was not evident in all cases. It could be calculated that, with the PCR method used, 0.04% [95% (confidence interval 0.00-2.03)] of the male embryos would erroneously be diagnosed as female if analysis is performed on two cells. The calculated chance for total amplification failure, if two cells are used for analysis, would be 1.4% [95% (confidence interval 0.04-8.04)]. The mouse embryo model proved to be a helpful tool to develop skills in the application of PCR for preimplantation genetic diagnosis at the single cell level. PMID- 7782462 TI - Non-syncytial sources of fetal DNA in transcervically recovered cell populations. AB - We have previously shown that fetal DNA can be detected in swabs and flushings obtained from the lower uterine pole prior to the termination of pregnancy. The presence of syncytiotrophoblast vesicles in transcervically retrieved samples suggested that this distinctive placental tissue was an abundant source of fetal DNA and a valuable resource in prenatal diagnosis strategies. In a more extensive study involving 150 terminations of pregnancy between 7 and 17 weeks gestational age, 29% of transcervically retrieved samples contained visible syncytial vesicles. Flushing of the uterine pole more frequently contained syncytia than direct aspiration (39% compared with 26% of samples) but this difference was not statistically significant. No samples > 14 weeks gestational age contained syncytia. Polymerase chain reaction analysis using Y-sequence specific-nested primers indicated the presence of fetal DNA in the absence of intact syncytial vesicles. We therefore examined samples by in-situ hybridization using Y-specific DNA probes. Positive labelling was observed in syncytial vesicles where present and in clumps of unidentified fetal cells. In addition, high numbers of naked nuclei were labelled in samples devoid of syncytia. These isolated nuclei are possibly derived from disrupted syncytia, and may be an important and hitherto overlooked contributory factor in fetal material which collects at the lower uterine pole. PMID- 7782463 TI - The effect of administration method: a comparison of the Rapaport and Exner Rorschach systems. AB - This study compared two Rorschach administration methods across a number of test variables. With a within-subjects, counter-balanced design, 20 female subjects randomly received either an initial Rapaport (Rapaport, Gill, & Schafer, 1968) or an Exner (Exner, 1974, 1986) Rorschach administration. Results showed that the Exner administration produced significantly more Color (C), Shading (Shd), and Blend (B) responses than did the Rapaport administration. Intersystem differences were most prominent on the first presentation of the two administrations. The first Exner administration produced significantly more C, Shd, and Blend responses than did the first Rapaport administration. Findings are discussed in light of their clinical implications, limitations in the experimental design, and suggestions for improving future research. PMID- 7782464 TI - Koppitz scoring system as a measure of Bender-Gestalt performance in behaviorally and emotionally disturbed adolescents. AB - Data are presented to assess the use of the Koppitz scoring system for the Bender Gestalt Test in a sample (N = 87) of behaviorally and emotionally disturbed adolescents. Results suggested that age was modestly related to Koppitz Developmental scores, an indication that visual-motor skills continue to develop beyond age 11. Scores were related to spatial perception skills as measured on the WISC-R. Gender, primary psychiatric diagnosis, educational tests, and MMPI scores were not related to Bender performance. Findings are discussed in terms of a need for additional research into the utility of the Bender as a measure of visual-motor skills in adolescents. PMID- 7782465 TI - Temperament and IQ mediate the effects of family history of substance abuse and family dysfunction on academic achievement. AB - In this study of sons of substance-abusing (n = 57) and normal (n = 71) fathers, it was hypothesized that sons' positive affective temperament (PAT) and intellectual ability (FSIQ) would mediate the effects of paternal substance abuse and family dysfunction on sons' reading achievement scores. Hierarchical, linear, and path analytic regression analyses were computed to test the hypotheses. It was found that (1) sons' FSIQ and PAT each partially mediated the effects of paternal substance abuse on sons' reading achievement scores and (2) that sons' PAT mediated the relationship between family dysfunction and their reading achievement scores. Because reading achievement is pivotal to academic success and school failure is associated with early age substance use, the importance of identifying processes that promote academic success is discussed. PMID- 7782466 TI - Comparability of correlates of original and revised Wechsler Adult Intelligence Scales in an alcohol-abusing population. AB - The correlates of the original and revised Wechsler scales were investigated among a sample of alcohol abusers referred for assessment of possible intellectual impairment. Fifty of the subjects were assessed with the original scale, while 44 were examined with the revised scale. The correlates of the two scales with other intellectual, demographic, and drinking variables suggested that the established correlates of the original scale may be cautiously assumed to hold for the revised version. PMID- 7782467 TI - Optimistic explanatory style and the perception of health problems. AB - Eighty-six adults completed questionnaires that measure explanatory style and perception of health problems. Subjects on the average saw themselves as below average in risk for a variety of health problems. Those subjects with an optimistic explanatory style, who explained bad events with external, unstable, and specific causes, in particular saw themselves as less at risk (r = .30, p < .01). They also believed that they were more able to prevent these health problems. Partialling out perceived preventability reduced to nonsignificance the correlation between explanatory style and perceived risk, which suggests that perceived preventability may mediate this link. PMID- 7782468 TI - Psychometric characteristics of the trait version of the Depression Adjective Check Lists (DACL) in adult psychiatric outpatients. AB - Psychometric characteristics of the trait version of Set 2 (E, F, G) of the Depression Adjective Check Lists (DACL) were studied in a sample of 177 consecutive admissions to a university medical center clinic of adult psychiatric outpatients (60 males, 117 females). The SCL-90-R and the Psychiatric Diagnostic Interview also were administered. The trait DACL was shown to have high internal consistency (.90 to .92) and alternate form reliability (.86 to .92) and good concurrent (.76) and discriminant validity. The DACL (E, F, G) was able to differentiate between those with or without the presence of a Major Depression. There was a significant correlation between DACL E and levels of distress and psychopathology. In addition, the magnitude of DACL score significantly differentiated psychiatric diagnostic groups. PMID- 7782469 TI - Comparison of depression in the community-dwelling and assisted-living elderly. AB - Depressive affect in assisted living (n = 351) and community dwelling (n = 102) elderly was compared by means of the state and trait forms of Set 1 of the Depression Adjective Check Lists (DACL). Four separate analyses of covariance (age as covariate) showed the main effects of living arrangement and form to be significant on each of the four lists. Assisted living and the state form were significantly higher. Sex was not significant on any of the lists, and none of the two-way and three-way interactions reached significance. Implications of the findings for program planning for the elderly in assisted living arrangements are discussed. PMID- 7782470 TI - Reliability of observer ratings in the assessment of personality disorders: a preliminary study. AB - A 200-item, self-report personality disorder inventory (Coolidge Axis II Inventory; CATI) was administered to 52 married target subjects. Their spouses and a close friend completed a significant-other form about the targets. The mean correlation across all personality disorder scales was .51 for the targets spouses, .36 for the targets-friends, and .41 for the spouses-friends. Twenty eight target-spouse correlations were significant and ranged from .99 to -.40. The mean correlation for the individual 13 personality disorder scales was .46 for target-spouses and ranged from .63 for the histrionic scale to .27 for the paranoid scale. The results were interpreted as establishing a basis for significant other assessment of personality disorders. PMID- 7782471 TI - Multidimensional Pain Inventory profile classifications and psychopathology. AB - The Multidimensional Pain Inventory (MPI) and the MMPI have been used widely to assess chronic pain patients. This study examined the relationship between patient profile classifications generated by the MPI and psychopathology as measured by the MMPI. MPI Dysfunctional and Interpersonally Distressed means were significantly different than the MPI Adaptive Coper means on scales 4, 6, 7, and 8 of the MMPI. The Dysfunctional and Adapative Coper means were also significantly different on MMPI scale 2. MMPI profiles for 79% classified as Dysfunctional and 62% classified as Interpersonally Distressed displayed psychopathology as defined by significant two-point scale elevations. Only 23% of those classified as Adaptive Copers had significant two-point MMPI scale elevations. PMID- 7782472 TI - The Social Support Appraisals Scale: construct validation for psychiatric inpatients. AB - The concept of social support and its relationship to physical health and psychological well-being has been well documented. However, little empirical research has been conducted with clinical populations, and no measure of perceived social support reportedly has been validated on psychiatric inpatients. A psychometric investigation of the Social Support Appraisals Scale, a subjective measure of social support, was undertaken with psychiatric inpatients. Good reliability and appropriate subscale intercorrelation were indicated by the data. Evidence of construct validity included significant associations with another social support appraisal measure, measures of other social support dimensions, and family-reported data. Strong psychometric properties of the instrument were demonstrated for hospitalized psychiatric patients. Clinical implications for prevention and treatment are discussed. PMID- 7782473 TI - The effect of PTSD and combat level on Vietnam veterans' perceptions of child behavior and marital adjustment. AB - This study empirically investigated the effects of post-traumatic stress disorder (PTSD) and combat level on Vietnam veterans' perceptions of their children's behavior, as well as its effects on their marital adjustment. Results indicated that the predictor variables of PTSD and combat level together explained 33.6% of the variance in perceived child behavior problems (p < .001) and 51.8% of the variance in marital adjustment (p < .001). In addition, PTSD and combat level, when observed together, reliably predicted internalizing and externalizing behavior problems in addition to four specific areas of marital adjustment. When observed individually, however, it was shown that child behavior problems and marital adjustment were predicted primarily by PTSD, rather than combat level. PMID- 7782474 TI - Interrelationship of MMPI-2 validity scales in personal injury claims. AB - A sample of MMPI-2s of worker's compensation and personal injury cases (N = 289) was gathered to examine the relationship of various indicators of exaggeration. Intercorrelations of the F, F-K, the MMPI Dissimulation Scale-revised (Ds-r), total of obvious minus subtle scales (O-S), Fake Bad Scale (FBS), VRIN, and TRIN were computed and the relative sensitivity of each score calculated using various cut-offs. Factor analysis suggests that malingering may take the form of inconsistent responding as well as symptom exaggeration. Patients evaluated at the request of plaintiff attorneys showed a seemingly greater degree of symptom exaggeration and inconsistent responding than did those referred by defense counsel. PMID- 7782475 TI - Discrimination of cortical from subcortical dementias on the basis of memory and problem-solving tests. AB - This study compared the discriminative utility of problem-solving and memory tasks in patients with Alzheimer's and Huntington's disease and in age-, education-, and gender-matched normal control subjects. Problem-solving was assessed with a modified version of the Wisconsin Card Sorting Test. Memory was measured with a 10-item, 6-trial version of the Buschke Selective Reminding Test. Receiver Operating Characteristic curves were plotted to determine which measure provided the highest sensitivity (i.e., hit rate) and specificity (i.e., correct rejection rate). Both tests provided excellent detection of dementia (88 to 98% classification accuracy), but were less robust in differentiating between dementia groups. Findings underscore the suitability of both measures to detect mild dementia, but emphasize the importance of specific memory measures to differentiate between cortical and subcortical dementia. PMID- 7782476 TI - The impact of constructional impairment on the WMS-R Visual Reproduction subtests. AB - The present study investigated the impact of constructional impairment on performance on the WMS-R Visual Reproduction subtests that measure memory for visual material. Thirteen subjects with constructional impairment had lower scores on the immediate and half-hour delayed Visual Reproduction subtests, relative to a cognitively comparable group of subjects without constructional impairment. However, the two groups did not differ with respect to their performance on the WMS-R Logical Memory subtests, which measure verbal memory. The implications of these modality specific findings among subjects with constructional impairment are discussed, and recommendations for clinicians who utilize the WMS-R are provided. PMID- 7782477 TI - Validation of an item-reduction short form of the Stanford-Binet Intelligence Scale: Fourth Edition with college students. AB - This study investigated the comparability of item-reduction and subtest-reduction short forms of the Stanford-Binet Intelligence Scale: Fourth Edition (SB:IV) with the complete battery in a sample of college students. All item-reduction SASs were not significantly different from the full battery SASs. Correlations for corresponding SASs and subtests between the complete and short form were highly significant, and analyses of the short-form profile supported the interpretation of individual subtests. The subtest-reduction short-form SASs were significantly lower than both the item-reduction short form and the full battery. Thus, an item reduction short form proved to be a more comparable estimate of the full battery composite than the subtest-reduction short form. PMID- 7782478 TI - Base rates of the WAIS-R intersubtest scatter and VIQ-PIQ discrepancy in normal elderly. AB - This study provides base rates for WAIS-R VIQ-PIQ discrepancy and for 3 indices of intersubtest scatter in a sample of high functioning normal elderly. High correlations between indices of scatter, such as (1) range of scatter; (2) Profile Variability Index; and (3) number of subtest scores that significantly deviated from the individual's own mean, indicate that easy-to-compute range can be used as an adequate measure of scatter in many clinical settings. The results suggest that bright elderly individuals display a large degree of scatter. The clinician should base judgment regarding abnormality of the WAIS-R indices on the rarity of the value demonstrated by the individual with respect to the sample of comparable age and intelligence level. PMID- 7782479 TI - The relationship between psychometric intelligence and the five-factor model of personality in a rehabilitation sample. AB - WAIS-R and NEO Personality Inventory (NEO-PI) scores obtained from 85 rehabilitation clients of the Evaluation and Development Center of Southern Illinois University's Rehabilitation Institute were utilized to examine the relationship between psychometric intelligence and personality. Correlational analyses revealed that the NEO-PI Openness domain and its six facets significantly correlated with WAIS-R FSIQ, VIQ, PIQ, and 9 of the 11 subtests. Multiple regression analyses showed that the five NEO-PI domains accounted for significant proportions of WAIS-R, FSIQ, VIQ, and PIQ score variance. The NEO-PI Openness domain was found to be the best predictor of WAIS-R FSIQ, VIQ, and PIQ scores. The study concludes with a discussion of the meaning and implications of the findings and suggestions for future research. PMID- 7782481 TI - Personality assessment of children with attention deficit hyperactivity disorder. AB - The present research was designed to assess several potentially important factors in the personality structure of a sample of children with attention deficit hyperactive disorder (ADHD) as compared to normal control children. Three questionnaires were administered to a group of 28 ADHD boys and to a control group of 83 boys: (1) The Locus of Control Scale for Children; (2) The Revised Children's Manifest Anxiety Scale; and (3) The Persistence Scale for Children. Results showed that the ADHD children had significantly higher external locus of control, were significantly less persistent, and reported an elevated level of "concentration/social worry" (an anxiety subscale). Such findings can help to clarify both the personality structure and the coping styles of the ADHD child. PMID- 7782480 TI - A comparison of the performance of cognitively disabled children on the WISC-R and WISC-III. AB - This study compared differences in performance on the WISC-III and on the WISC-R. Sixty-one students with learning impairments, due for reevaluation of their special education placement, were administered the WISC-III as part of a psychological assessment battery. Results indicate a mean difference between WISC R and WISC-III FSIQ of 7.95 points, which is similar to WISC/WISC-R comparisons. Substantial differences that averaged 9.21 points were found between WISC-R and WISC-III PIQ means. These findings suggest that for a special education sample an average decrease of at least 8 points can be expected on the WISC-III Full Scale IQ. Caution should be exercised when one is considering changes in educational classification or interpreting qualitative differences in performance on WISC-III scores compared with WISC-R scores. PMID- 7782482 TI - The safety of concomitant use of sumatriptan and antidepressant treatments. AB - It is presently contraindicated to use the antimigraine drug sumatriptan with selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or lithium. Consequently, many patients undergoing these pharmacotherapies for psychiatric disorders may not benefit from the therapeutic effect of sumatriptan in acute migraine attacks. Because sumatriptan does not appear to cross the blood brain barrier and has a short half-life, it was deemed relatively safe to prescribe sumatriptan with antidepressant treatments. Fourteen patients receiving fluoxetine, fluvoxamine, sertraline, moclobemide, lithium, or buspirone did not experience significant side effects when they took oral sumatriptan for the relief of migraine on a total of 103 episodes. It is concluded that the combined use of sumatriptan with the above-mentioned antidepressant treatments may be safe. PMID- 7782483 TI - The efficacy and safety of divalproex sodium in the treatment of acute mania in adolescents and young adults: an open clinical trial. AB - This open clinical trial investigated the potential short-term efficacy and safety of divalproex sodium in the treatment of adolescents and young adults with bipolar affective disorder in an acute manic phase. Fifteen subjects were treated for 7 weeks with divalproex sodium (mean drug level in blood +/- the standard deviation at trial completion, 642.85 +/- 183.08 mumol/liter) and were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment Scale (GAS), and the Clinical Global Impressions Scale (CGI). Of the 15 subjects who entered the study, 8 showed marked improvement on the MMRS (pre-post decrease of > or = 75%), 4 showed moderate improvement (pre-post decrease of 50 to 74%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 showed no improvement and was withdrawn before the seventh study week because of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in the 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.08 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 to 12.00 +/- 4.22; t = 7.53; p < 0.0001), the GAS (30.23 +/- 9.05 to 54.69 +/- 9.40; t = 7.50; p < 0.0001), and the CGI (5.38 +/- 0.96 to 2.38 +/- 0.87; t = 10.01; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782484 TI - Comparative abuse liability of sertraline, alprazolam, and dextroamphetamine in humans. AB - Sertraline is an effective antidepressant acting as a selective serotonin reuptake inhibitor. The subjective and behavioral effects of sertraline were studied and compared with the effects of alprazolam and dextroamphetamine in a within-subject, randomized, double-blind study in 20 volunteers aged 18 to 46 years. These subjects were experienced but nondependent users of central nervous system depressants who had the ability to reliably distinguish secobarbital, 150 mg, from placebo and to report positive subjective effects of secobarbital in an experimental setting. The following drug conditions were tested: sertraline, 100 and 200 mg; alprazolam, 1 mg; dextroamphetamine, 10 mg; and placebo. Drug effects were assessed with an objective test of psychomotor performance, subject-rated questionnaires, and observer-rated scales. Both alprazolam and dextroamphetamine were distinguishable from placebo on most measures, but sertraline produced effects discernable from placebo on only a few measures. At 1 hour postdrug administration, dextroamphetamine and alprazolam produced positive effects on several measures of elation, euphoria, and drug liking greater than placebo and both doses of sertraline. In contrast, sertraline produced higher scores on measures of dysphoria and physical unpleasantness than did the other drug conditions. Observer ratings of satisfaction with the drug and other pharmacologic effects were consistent with these findings. Results from this study indicate that sertraline, at the doses tested, does not possess the behavioral effects profile considered to be indicative of abuse potential when compared with alprazolam and dextroamphetamine. PMID- 7782485 TI - Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. AB - In vitro preparations of human liver microsomes were used to study the inhibiting effects of two selective serotonin reuptake inhibitor (SSRI) antidepressants, paroxetine and fluvoxamine, on metabolism via hydroxylation of alprazolam and of desipramine. These reactions are mediated by Cytochromes P450-3A4 and P450-2D6, respectively. Paroxetine was a highly potent inhibitor of desipramine hydroxylation; the inhibition constant (Ki) value of 2.0 microM indicated greater inhibiting potency than fluoxetine or norfluoxetine. The in vitro data predicted in vivo impairment of desipramine clearance by coadministration of paroxetine which was in the same range as observed in a clinical study. Fluvoxamine, by contrast, was a much weaker inhibitor of desipramine hydroxylation, having a Ki value (16.6 microM) similar to those of sertraline and desmethylsertraline. For hydroxylation of alprazolam, paroxetine was a relatively weak inhibitor, approximately comparable to fluoxetine, whereas fluvoxamine showed inhibiting capacity similar to that of norfluoxetine. The in vitro data predicted the degree of impairment of alprazolam clearance observed in vitro model can therefore provide clinically relevant data on prediction of potential drug interactions with SSRIs. PMID- 7782486 TI - Antagonizing the effects of experimentally induced sleep disturbance in healthy volunteers by lormetazepam and zolpidem. AB - The effects on sleep of two well known hypnotics, lormetazepam and zolpidem, during experimentally induced environmental noise were compared with placebo. In a double-blind, crossover study, 12 normal volunteers were subjected to prerecorded traffic noise with a mean noise level of 52 dB(A) and peaks to 77 dB(A) continuously for 8 hours in bed. Both hypnotics increased total sleep time, predominantly stage 2 sleep. A significant decrease in the number of sleep stage transitions, arousals, and awakenings longer than 3 minutes was found only with lormetazepam. No significant effects on rapid eye movement (REM) and slow wave sleep were observed. Latencies to persistent sleep and REM sleep onset were not different for either active treatment compared with placebo. Only after lormetazepam was performance on the morning reaction time test significantly affected. However, no differences were found in the subjective sleep quality and alertness ratings. Changes in the distribution of sleep stages throughout the night were related to the elimination half-life characteristics of the hypnotics, but few trends were detected. Both the protective properties against environmental noise of the hypnotics studied and the validity of the model of induced sleep disturbance in evaluating hypnotic agents are discussed. PMID- 7782488 TI - A clinically significant interaction between clozapine and valproate. PMID- 7782487 TI - Hypothesized interaction between valproic acid and warfarin. PMID- 7782489 TI - Improved efficacy and fewer side effects under clozapine treatment after addition of fluvoxamine. PMID- 7782490 TI - Thrombocytopenia and delirium associated with tranylcypromine overdose. PMID- 7782491 TI - Response to "Sertraline and isocarboxazid cause a serotonin syndrome". PMID- 7782493 TI - Canny cases. Case 4: A precipitate poisoning. PMID- 7782492 TI - Bromocriptine for prolactinoma-related dissociative disorder and depression. PMID- 7782494 TI - The Helsinki Declaration: timeless guide or irrelevant anachronism? PMID- 7782495 TI - Desipramine treatment of major depression in patients over 75 years of age. AB - The authors investigated the relationship of desipramine concentrations in plasma to response, side effects, and dose in depressed patients over 75 years of age to determine if these "very old" patients were unusually sensitive to treatment. Thirty-four elderly patients consecutively hospitalized for nonpsychotic, unipolar major depression were treated with a fixed dose desipramine regimen for 4 weeks. Twelve nonresponding patients received a second trial at an increased dose. Comparisons were made with data from younger patients previously published by the authors. At comparable doses, steady-state desipramine concentrations in plasma in the elderly patients did not differ from those observed in younger patients. Response at levels in blood < 115 ng/ml was low, only 6 (21%) of 28 patient trials resulted in response. At levels > or = 115 ng/ml, 6 (46%) of 13 patient trials were effective. These rates were not significantly different. Inspection of the data revealed that a concentration in plasma of 105 ng/ml significantly separated responders and nonresponders (chi 2 = 3.93, df = 1, p < 0.05), but even at levels > or = 105 ng/ml, the response rate was still low relative to rates in prior studies of younger patients treated for a similar duration. The serious adverse reaction rate, 7 of 34, was similar to that previously observed in younger patients. This sample of "very old" elderly was not unusually "sensitive" to antidepressant drug treatment. In fact, the low rate of response observed at usually adequate levels in blood suggested "resistance" to treatment. The findings underscore the need for more effective drug treatments in the depressed elderly. PMID- 7782496 TI - Metabolic mapping of visual areas in the behaving cat: a [14C]2-deoxyglucose study. AB - Visually responsive cortical areas and subcortical nuclei were studied in the awake cat using the 2-deoxyglucose technique. Visual input was confined to one hemisphere by unilaterally sectioning the optic tract, the corpus callosum and the commissura anterior. Within the intact hemisphere, numerous cortical regions were distinguishable in the autoradiographs due to differential labelling. Comparison of the intact with the visually deafferented hemisphere confirmed the visual character of eighteen cortical areas (areas 17, 18, 19, 20a, 20b, 21a, 21b, the posteromedial lateral, posterolateral lateral, anteromedial lateral, anterolateral lateral, dorsal lateral, ventral lateral, and posterior suprasylvian areas, the splenial and anterior ectosylvian sylvian areas, insular visual area and posterior area 7) and revealed the visual nature of an area in the posterior cingulate gyrus which had not been described previously. We refer to this area as cingulate visual area (CVA). This area exhibits a gradient in interhemispheric differences along a caudorostral axis similar to that observed in posterior area 7 which is in keeping with the strong and topographic connections between CVA and posterior area 7. These results support the validity of metabolic mapping for the characterisation of cortical areas. PMID- 7782497 TI - Abnormal ipsilateral visual field representation in areas 17 and 18 of hypopigmented cats. AB - We compared the central projections of retinal ganglion cells in temporal retina and the cortical representation of visual fields in areas 17 and 18 in cats with various hypopigmentation phenotypes (albino, heterozygous albino, Siamese, and heterozygous Siamese). In all cats studied, we found that the extent of abnormal ipsilateral visual field representation varied widely, and more of the ipsilateral visual field was represented in area 18 than in area 17. The greatest degree of ipsilateral visual field representation was found in albino cats, followed by Siamese, heterozygous albino and heterozygote Siamese cats, respectively. Additionally, in the different groups there was wide variation in the numbers of contralaterally projecting alpha and beta ganglion cells in temporal retina. In all cases, however, contralaterally projecting alpha cells were found to extend further into temporal retina than beta cells. We found that in each cat studied, the maximum extent of the abnormal ipsilateral visual field representation in areas 18 and 17 corresponded to the location of the 50% decussation line (i.e., the point where 50% of the ganglion cells in temporal retina project to the contralateral hemisphere) for alpha and beta cells, respectively, for that cat. Our results suggest that the extent of the abnormal visual field representations in visual cortex of hypopigmented cats reflects the extent of contralaterally projecting retinal ganglion cells in temporal retina. PMID- 7782498 TI - Synapses on axons of sympathetic preganglionic neurons in rat and rabbit thoracic spinal cord. AB - Axosomatic and axodendritic synapses occur on sympathetic preganglionic neurons, but it is not yet known whether their axons receive synaptic input, which could be particularly effective at regulating sympathetic outflow. Here, we examined retrogradely labelled sympathetic preganglionic axons to see if they received synapses. Cholera toxin B subunit (CTB) or CTB conjugated to horseradish peroxidase (CTB-HRP) was used to label neurons projecting to the rat or rabbit superior cervical ganglion, the rat adrenal medulla, or the rabbit stellate ganglion. At the light microscopic level, small groups of CTB-immunoreactive axons travelled through the ventral horn near its lateral boundary, with occasional axons taking a more medial course. The axons passed through the ventrolateral funiculus to exit at the ventral roots. In parasagittal section, a few axons branched within the ventral horn, sending processes rostrally and caudally for short distances before they turned ventrally to exit the spinal cord. At the ultrastructural level, CTB-immunoreactive rat and rabbit sympathetic preganglionic axons were almost exclusively unmyelinated. In contrast, labelling with CTB-HRP revealed both myelinated and unmyelinated axons in the ventral horn, the ventrolateral white matter, and the ventral roots. CTB-HRP also allowed the detection of the initial segment of a sympathetic preganglionic axon. Synapses, with vesicles clustered presynaptically and membrane specializations postsynaptically, were found on some unmyelinated CTB-immunoreactive axons. Occasional axons received several synapses. Synapses were most common on CTB containing axons just ventral to the intermediolateral cell column. One synapse was found on an axon within 2 microns of its origin from a proximal dendrite. Rare synapses were found several hundred micrometers ventral to the intermediolateral cell column. One branching axon had synapses just below the branch point on both the main axon and the axonal branch. These findings indicate an extensive synaptic input to the axons of at least some sympathetic preganglionic neurons. These axoaxonic synapses could have a profound effect on sympathetic activity. PMID- 7782500 TI - Regenerative axonal sprouting in the cat trochlear nerve. AB - Following peripheral trochlear nerve axotomy in the cat, the normal number of myelinated axons is restored despite significant motor neuron death, suggesting regulation of the number of myelinated axons in the regenerated nerve. In this study we used light and electron microscopy to examine the production and maintenance of axonal sprouts at different locations in the nerve and at different postoperative intervals. Despite proliferative sprouting and an overproduction of nonmyelinated axons in the regenerating trochlear nerve, the number of myelinated axons was strictly regulated. Only approximately 1,000 regenerated axons were eventually remyelinated, but many nonmyelinated axons were still present 6-8 months postaxotomy. Regenerated axons were remyelinated in a proximal-to-distal direction between 3 and 4 weeks postaxotomy. We also examined the maturation of regenerated myelinated axons by measuring axon diameter and myelin index (an expression of myelin thickness). Mean myelinated axon diameter remained significantly below normal in long-term regenerated nerves. Mean myelin index was not different from normal at 4 weeks postaxotomy but was significantly decreased at long postoperative intervals, reflecting a slightly thicker myelin sheath relative to the axon diameter. This relative increase in mean myelin thickness could serve to restore normal conduction velocity despite the decrease in mean axon diameter. We suggest that the regulation of the number of myelinated axons at the normal number despite cell death and the increase in mean myelin thickness may both be compensatory mechanisms that function to restore preoperative conditions and maximize functional recovery. PMID- 7782499 TI - Origin of microglia in the quail retina: central-to-peripheral and vitreal-to scleral migration of microglial precursors during development. AB - The origin, migration, and differentiation of microglial precursors in the avascular quail retina during embryonic and posthatching development were examined in this study. Microglial precursors and developing microglia were immunocytochemically labeled with QH1 antibody in retinal whole mounts and sections. The retina was free of QH1+ macrophages at embryonic day 5 (E5). Ameboid QH1+ macrophages from the pecten entered the retina from E7 on. These macrophages spread from central to peripheral areas in the retina by migrating on the endfeet of the Muller cells and reached the periphery of the retina at E12. While earlier macrophages were migrating along the inner limiting membrane, other macrophages continued to enter the retina from the pecten until hatching (E16). From E9 on, macrophages were seen to colonize progressively more scleral retinal layers as development advanced. Macrophages first appeared in the ganglion cell layer at E9, in the inner plexiform layer at E12, and in the outer plexiform layer at E14. Therefore, it seems that macrophages first migrated tangentially along the inner retinal surface and then migrated from vitreal to scleral levels to gain access to the plexiform layers, where they differentiated into ramified microglia. Macrophages appeared to differentiate shortly after arrival in the plexiform layers, as poorly ramified QH1+ cells were seen as early as E12 in the inner plexiform layer and at E14 in the outer plexiform layer. Radial migration of macrophages toward the outer plexiform layer continued until posthatching day 3, after which retinal microglia showed an adult distribution pattern. We also observed numerous vitreal macrophages intimately adhered to the surface of the pecten during embryonic development, when macrophages migrated into the retina. These vitreal macrophages were not seen from hatching onwards, when no further macrophages entered the retina. PMID- 7782501 TI - Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons. AB - Metabotropic glutamate receptors (mGluRs) mediate the effects of glutamate neurotransmission on intracellular second messenger systems. Among the seven distinct mGluR receptor isoforms currently identified, the mGluR5 isoform is expressed particularly prominently in the striatum, where it may contribute to neuronal plasticity, motor behaviors, and excitotoxic injury. mGluR5 mRNA expression in striatal enkephalinergic, somatostatinergic, and cholinergic neurons was examined using double label in situ hybridization techniques. mGluR5 expression is abundant in a large number of medium-sized striatal cells but is absent in a significant minority of neurons. Double label in situ hybridization with 35S-dATP- and digoxygenin-dUTP-tailed oligonucleotide probes demonstrated that mGluR5 message is highly expressed by enkephalinergic striatal neurons but is not detectable in cholinergic or somatostatin interneurons. In addition, some nonenkephalin, presumably substance P, neurons were also strongly labeled for mGluR5. The differential expression of mGluR5 in striatal projection neurons vs. interneurons may contribute to the selective vulnerability of these neurons to disease processes. PMID- 7782502 TI - Neuropeptide receptors in developing and adult rat spinal cord: an in vitro quantitative autoradiography study of calcitonin gene-related peptide, neurokinins, mu-opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors. AB - A number of neuroactive peptides including calcitonin gene-related peptide (CGRP), substance P, neurokinin B, opioids, somatostatin (SRIF), galanin, neurotensin and vasoactive intestinal polypeptide (VIP) have been localized in adult rat spinal cord and are considered to participate either directly and/or indirectly in the processing of sensory, motor and autonomic functions. Most of these peptides appear early during development, leading to the suggestion that peptides, in addition to their neurotransmitter/neuromodulator roles, may possibly be involved in the normal growth and maturation of the spinal cord. To provide an anatomical substrate for a better understanding of the possible roles of peptides in the ontogenic development of the cord, we investigated the topographical profile as well as variation in densities of [125I]hCGRP alpha, [125I]substance P/neurokinin-1 (NK-1), [125I]eledoisin/neurokinin-3 (NK-3), [125I]FK 33-824 ([D-Ala2, Me-Phe4, Met(O)ol5]enkephalin)/mu-opioid, [125I]galanin, [125I]T0D8-SRIF14 (an analog of somatostatin); [125I]neurotensin and [125I]VIP binding sites in postnatal and adult rat spinal cord using in vitro quantitative receptor autoradiography. Receptor binding sites recognized by each radioligand are found to be distributed widely during early stages of postnatal development and then to undergo selective modification to attain their adult profile of distribution during the third week of postnatal development. The apparent density of various receptor sites, however, are differently regulated depending on the lamina and the stage of development studied. For example, the density of mu-opioid binding sites, following a peak at postnatal day 4 (P4), declines gradually in almost all regions of the spinal cord with the increasing age of the animal. [125I]substance P/NK-1 binding sites, on the other hand, show very little variation until P14 and then subsequently decrease as the development proceeds. In the adult rat, most of these peptide receptor binding sites are localized in relatively high amounts in the superficial laminae of the dorsal horn. To varying extents, moderate to low density of various peptide receptor binding sites are also found to be present in the ventral horn, intermediolateral cell column and around the central canal. Taken together, these results suggest that each receptor-ligand system is regulated differently during development and may each uniquely be involved in cellular growth, differentiation and in maturation of the normal neural circuits of the spinal cord. Furthermore, the selective localization of various receptor binding sites in adult rat spinal cord over a wide variety of functionally distinct regions reinforces the neurotransmitter/modulator roles of these peptides in sensory, motor and autonomic functions associated with the spinal cord. PMID- 7782504 TI - The fate of potentially pathogenic bacteria in Swiss hard and semihard cheeses made from raw milk. AB - This study examined the ability of potentially pathogenic bacteria to grow and to survive during the manufacture and ripening of Swiss hard and semihard cheese varieties made from raw milk. The results show that hard cheeses are hygienically safe; 1 wk after fabrication, the inoculated pathogens (Aeromonas hydrophila. Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella spp., Staphylococcus aureus, and Yersinia enterocolitica) could no longer be detected. At the age of commercial ripeness, the semihard cheeses were free from the inoculated pathogens and their toxic metabolites, except for L. monocytogenes, which survived the manufacturing and ripening process. PMID- 7782503 TI - Distribution and effects of tachykinin-like peptides in the stomatogastric nervous system of the crab, Cancer borealis. AB - The rhythmically active pyloric and gastric mill motor patterns in the stomatogastric ganglion of the crab, Cancer borealis, are influenced by modulatory projection neurons whose somata are located primarily in the other ganglia of the stomatogastric nervous system. One of these projection neurons exhibits substance P-like immunolabeling. However, bath application of substance P does not influence these motor patterns. To determine whether a different peptide is responsible for the substance P-like immunolabeling, we studied the presence and physiological effects of the locustatachykinins and the leucokinins, two families of tachykinin-like peptides originally identified in insect nervous systems. Locustatachykinin-like immunolabeling has the same distribution in the stomatogastric nervous system as substance P-like immunolabeling and colocalizes with it in the majority of immunopositive structures. Preincubation of locustatachykinin antibody with substance P, and preincubation of substance P antibody with locustatachykinin, blocks subsequent immunolabeling in the stomatogastric nervous system. In contrast, we found no leucokinin-like immunolabeling in this system. Bath application to the stomatogastric ganglion of individual locustatachykinins or leucokinins excited the pyloric rhythm in a state-dependent manner. Each peptide family had distinct effects on the pyloric rhythm. Thus, both of these tachykinin-like peptide families are likely related to native neuropeptides that influence the pyloric rhythm. Furthermore, a member of the locustatachykinin family is likely to be the source of the previously identified substance P-like immunoreactivity in the stomatogastric nervous system. PMID- 7782505 TI - Effect of individual caseins on plasminogen activation by bovine urokinase-type and tissue-type plasminogen activators. AB - The effect was examined of individual caseins on the rate of plasminogen activation by bovine urokinase-type and tissue-type plasminogen activators. All individual caseins (alpha-CN, beta-CN, and kappa-CN) enhanced the activity of both types of plasminogen activators. Optimal concentrations for alpha-CN and beta-CN were 5 and 25 micrograms/ml, respectively. The enhancement of enzymatic activity declined when concentrations of alpha-CN and beta-CN were higher. In contrast, increasing concentrations of kappa-CN from 0 to 200 micrograms/ml resulted in corresponding increases in activity of both types of plasminogen activators. On a weight basis, alpha-CN was the most effective enhancer of plasminogen activator activity. Indirect evidence obtained with experiments utilizing alpha-CN immobilized on agarose suggested that the effect is related to extensive binding of plasminogen and both types of plasminogen activators to casein. PMID- 7782506 TI - Immunomodulation of human blood cells following the ingestion of lactic acid bacteria. AB - Because of the lack of data that convincingly show immunomodulatory properties of lactic acid bacteria in humans, a study was performed in which healthy volunteers were divided into two groups and given a fermented milk product supplemented with Lactobacillus acidophilus strain La1 or Bifidobacterium bifidum strain Bb 12 for 3 wk. Blood was sampled throughout the study to assess changes in lymphocyte subsets or leukocyte phagocytic activity following consumption of the fermented products. No modifications of lymphocyte subpopulations were detected. In contrast, phagocytosis of Escherichia coli sp. in vitro was enhanced after the administration of both fermented products. The increment in phagocytosis was coincident with fecal colonization by the lactic acid bacteria and persisted for 6 wk after ingestion of the fermented products. By this time, the fecal lactobacilli and bifidobacteria had returned to concentrations prior to consumption. Nonspecific, anti-infective mechanisms of defense can be enhanced by the ingestion of specific lactic acid bacteria strains. These strains can be used as nutritional supplements to improve the immune function of particular age groups, i.e., the neonate or the elderly, for which these functions are diminished. PMID- 7782507 TI - Vitamin A distribution among fat globule core, fat globule membrane, and serum fraction in milk. AB - In cream suspensions and partly skimmed milks obtained by successive centrifugation from whole milk, the concentration of vitamin A per gram of fat was inversely related to the mean size of fat globules. This result indicated that not all the vitamin A of milk was located in the fat globule core, which was further supported by studies of buttermilk and butter oil fractions obtained by churning of cream. These studies indicated that a portion of the vitamin A was associated with the fat globule membrane. The vitamin A content per gram of fat of purified fat globules was similar to vitamin A content per gram of fat of the whole milk from which they were isolated. This result indicated that the amount of vitamin A in the serum fraction was negligible and that vitamin A was localized in the fat globule and fat globule membrane. PMID- 7782508 TI - Preparation of casein using carbon dioxide. AB - The effects of pressure, temperature, residence time, and mass of skim milk on some characteristics of casein, prepared by precipitation with high pressure CO2, were examined in a batch reactor. For a 500-g milk sample, precipitation occurred at pressures > 2760 kPa and temperatures > 32 degrees C. Residence time was not significant and was held at 5 min. Yields were maximum at 2750 to 5520 kPa and at 38 to 49 degrees C for a 500-g milk sample. The resulting whey had a pH of 6.0. The casein product had an acceptable appearance and had greater solids, ash, and Ca contents than commercial acid caseins. Particle size distribution studies showed that the mean particle size was sensitive to precipitation pressure and temperature and was similar to that of acid caseins produced under laboratory conditions. The HPLC studies of the casein and whey fractions showed that precipitation by CO2 did not result in fractionation of casein or whey proteins to their component proteins. PMID- 7782510 TI - Characterization of clinical mastitis in primiparous heifers. AB - Using data from health records for cows in Finland from between 1983 and 1991, we investigated the general trend for frequency of mastitis in heifers, seasonal variation, breed differences, and etiology of the disease. The performance of the heifers was monitored during first lactation. Treatment of heifer mastitis, defined as mastitis treatment 1 wk before and 1 wk after calving, increased from 1.8 to 4.4% between 1983 and 1991. The increase can be partly attributed to increased milk production, subsequent reduced resistance to mastitis, and the general trend toward more efficient treatment of mastitis. Heifer mastitis was a characteristic disease of well-managed, productive herds with low SCC and a high frequency of mastitis treatments administered by a veterinarian. Of the feeding factors studied, only use of homemade concentrates was associated with higher mastitis frequency. Mastitic heifers had higher genetic potential for milk production than control heifers, but actual milk production was 70 to 80 kg lower than expected. Most mastitic heifers recovered well and were not more susceptible than control heifers to further incidence of mastitis or other diseases. However, heifer mastitis caused more heifers than usual to be culled. PMID- 7782509 TI - Enhanced antigen-specific responses in bovine mammary glands following administration of interleukin-2. AB - This study examined the feasibility of using interleukin-2 as a vaccine adjuvant to enhance specific immunity in the bovine mammary gland. In trial 1, cows were immunized by intramammary infusion of keyhole limpet hemocyanin with either saline (n = 3) or interleukin-2 (n = 3) as adjuvants. In trial 2, cows were immunized by intramuscular injection near the supramammary lymph node with keyhole limpet hemocyanin in conjunction with saline (n = 4). Freund's incomplete adjuvant (n = 4), or interleukin-2 (n = 4). Local immunization with interleukin-2 as an adjuvant significantly increased antibody titers in milk over preimmunization levels and levels in saline-treated cows. The use of Freund's incomplete adjuvant and interleukin-2 as adjuvants in cows that were immunized systemically enhanced both sera and lacteal antibodies to keyhole limpet hemocyanin. However, cows that were administered interleukin-2 responded more quickly than those given Freund's incomplete adjuvant. Only those cows that received interleukin-2 as an adjuvant demonstrated significant increases in blood lymphocyte proliferation to keyhole limpet hemocyanin, pokeweed mitogen, and interleukin-2. The results of these two trials suggest that immunization with interleukin-2 as an adjuvant may be more effective than Freund's incomplete adjuvant in enhancing specific immunity in the bovine mammary gland and may possibly be an effective adjuvant in mastitis immunization protocols. PMID- 7782511 TI - Estimates of variability for somatic cell count measurements in the Iowa dairy industry. AB - The SCC collected from 15 instruments in 12 laboratories were used to quantify accuracy, repeatability, and reproducibility in the Iowa dairy industry. For each of three trials, milk was sampled at the morning milking from 30 different Holsteins in the Iowa State University herd. Identified samples and unidentified duplicates were provided for each participating instrument. Mean SCC was 418,000 cells/ml, and mean SCC for duplicates ranged from 9000 to 3,966,000. Accuracy for a set of 30 duplicates was lowest for trial 1 (CV = 16.4%) and highest for trial 2 (CV = 7.6%). Intraclass correlations estimated repeatability and were .99 for all but one instrument. Coefficients of variation for repeatability (weighted mean = 11.4%) were similar to estimates for accuracy (weighted mean = 11.0%), but reproducibility was considerably lower (30.0%). Samples were classified by SCC as very low, < 125,000; low, 125,000 to 249,000; medium, 250,000 to 500,000; and high, > 500,000. Repeatability for high samples was higher than repeatability for very low SCC samples; coefficient of variation for high SCC samples was 6.8% but was > 25.0% for samples with < 500,000 cells. Repeatability was within standards set by the industry, but current procedures for quality control may not adequately address reproducibility. PMID- 7782512 TI - Body condition scores of Holstein cows on Prince Edward Island, Canada: relationships with yield, reproductive performance, and disease. AB - An observational study of 429 Holstein cows in 13 herds (mean 305-FCM yield of 7225 kg) was conducted to determine the relationship between body condition score and its changes with milk yield, reproductive performance, and disease incidence. Cows were scored once for body condition during the dry period, near calving, and then every 14 d until termination of lactation. Condition score at calving had no effect on either peak of 305-d milk yields. Condition loss averaged .73 and .83 points for primiparous and multiparous cows, respectively. The duration and magnitude of condition loss depended primarily on score at calving and was greater for cows that calved with higher condition scores. After reaching minimum score, cows gained an average of .53 condition points in the remainder of lactation. Total amount of gain was not affected by body condition score at calving or by milk yield. No significant differences were found for days to first observed estrus, days to first breeding, days to conception, or number of times bred for cows grouped by body condition score at calving or by condition loss between calving and first breeding. Body condition score at calving was not significantly different for diseased cows. Cows that were diagnosed with a disease lost more condition than undiseased cows, but the difference generally was < .25 points. PMID- 7782514 TI - Ruminally protected lysine and methionine for lactating dairy cows fed a diet designed to meet requirements for microbial and postruminal protein. AB - Dairy cows, 20 at each of two sites, were used to determine responses to ruminally protected Lys and Met in a full lactation study. Cows were fed corn silage twice daily for ad libitum intake and a concentrate four times daily in proportion to milk production. At Truro, cows were fed 2.7 kg/d of alfalfa and timothy hay DM at 0600 and at 1500 h. At Fredericton, cows were fed 2.7 kg of timothy silage DM at 0600 h and 2.7 kg of alfalfa hay DM at 1500 h. Diets were designed to meet, but not to exceed, recommendations for ruminally degradable CP and intestinally digestible protein. Ten cows at each site were fed ruminally protected L-Lys.HCl (19 g/d) and DL-Met (6.5 g/d). Cows fed AA at each site produced more milk, lactose, protein, and fat; milk protein and fat percentages were also higher. No time x treatment interactions occurred for any production parameter. In spite of similar production responses between sites, cows fed AA consumed more DM at Truro, but those at Fredericton did not. Thus, gross efficiency of utilization of dietary N for milk N was increased with AA at Fredericton but not at Truro. However, considering the increased intake of CP by cows fed AA at Truro, an event that would have been expected to depress efficiency of utilization of dietary N, the lack of difference at Truro between treatments can be interpreted as an improvement, relative to expectations, because of AA feeding. High producing dairy cows fed a diet that was adequate in CP responded to ruminally protected Lys and Met primarily with increased production of milk protein and fat throughout the full lactation. PMID- 7782513 TI - Effects of varying forage types on milk production responses to whole cottonseed, tallow, and yeast. AB - Four forage treatments (45% corn silage, 33.75% corn silage plus 11.25% alfalfa hay, 11.25% bermudagrass hay, or 11.25% cottonseed hulls on a DM basis) were arranged factorially with no added fat, 12.5% whole cottonseed, or 2.5% tallow. Different diets were fed during three 28-d periods to 20 control Holstein cows and to 20 cows receiving yeast continuously in a split-plot design. Milk yield of cows fed cottonseed hulls with corn silage was 2.4 kg/d higher than with corn silage plus bermudagrass hay and .7 kg/d higher than with corn silage only or corn silage plus alfalfa hay. Whole cottonseed depressed milk yield by 1 kg/d. Cows fed yeast had increased DMI, and yeast interacted with forage so that more milk was produced by cows fed alfalfa diets. Yeast depressed milk protein percentage. Holstein cows in a commercial Florida dairy were fed no yeast or 10 g/d continuously for 60 d; milk fat percentage was greater (3.51 vs. 3.37%) with yeast. In summary, effects on milk and SCM were positive when cottonseed hulls were utilized with corn silage, negative with whole cottonseed, and neutral with supplemental tallow. Yeast effects on SCM, although not significant for either experiment, tended to be positive for both (mean +1.2 kg/d per cow). PMID- 7782515 TI - Increased milk production of cows in early lactation fed chemically treated soybean meal. AB - Holstein cows in early lactation and producing about 35 kg/d of milk were fed TMR for ad libitum intake and 1 kg/d of long alfalfa hay. Soybean meal and soybean meal treated by a novel technique were compared in diets of 15 and 17% CP in a 2 x 2 factorial design. Digestibilities of DM, CP, and ADF were significantly lower for treated soybean meal diets. Mean DMI was about 21 kg/d and was unaffected by treatment. Milk production was significantly increased during wk 7 to 16 of lactation for cows fed treated soybean meal diets. The production of SCM and milk components was greater for cows fed treated soybean meal than for cows fed soybean meal, but the differences were not significant. By wk 16, compared with wk 3 of lactation, the persistency of production of milk and lactose was markedly increased by treated soybean meal. The persistency of milk protein production was 100.5% for cows fed the diet containing treated soybean meal at 17% CP and about 97% for the other diets. The hypothesis that Met supply was limiting secretion of milk protein in cows fed treated soybean meal is discussed. PMID- 7782517 TI - Performance of high producing dairy cows offered drinking water of high and low salinity in the Arava desert. AB - The effect of supplying high producing Israeli Holstein cows with desalinated or salty water on milk composition and production was examined in the Arava desert of southern Israel. Daily water consumption of cows offered desalinated water was higher by 10.6 L than that of the group offered salty drinking water; DMI was similar for the two groups. Daily production of milk and 3.5% FCM was higher for the cows receiving desalinated water than for the cows receiving salty water; 35.2 versus 33.1 kg and 31.6 versus 29.8 kg, respectively. The percentage of protein in milk and the daily protein production were higher for the cows receiving desalinated water than for the cows receiving salty water: 2.89% and 1.01 kg versus 2.84% and .93 kg, respectively. The percentage of milk fat and the daily fat production were higher for the cows receiving desalinated water. These results indicate that water salinity negatively affects milk production. Improvement of water quality by desalination increased production of milk and milk constituents. PMID- 7782518 TI - Effect of selenium supplementation of cows on maternal transfer of selenium to fetal and newborn calves. AB - A trial was conducted to determine the effect of maternal supplementation of Se on transfer of Se to the fetus during late gestation. Holstein cows were randomly assigned at dry-off to receive no Se or 3 mg/d of supplemental Se as selenite delivered via an intraruminal bolus. Supplementation significantly increased concentrations of Se in blood of dams at parturition. Similarly, calves of cows that were supplemented with Se had higher Se in blood and liver. Colostral concentrations of Se were increased by maternal Se supplementation; Se increased in the casein fraction. The Se concentrations in blood, plasma, and liver of calves were positively correlated with the Se concentrations in plasma of the dam at parturition. Concentrations of Se in colostrum and in calf liver also were closely correlated. Concentrations of Se in calf liver at d 42 were closely correlated with concentrations of Se in liver at birth. Maternal supplementation of Se increased Se reserves in the liver of the newborn and in colostrum. Carryover effects of Se supplementation of dams were evident in calves at 42 d of age. PMID- 7782516 TI - Acid-base status, renal function, water, and macromineral metabolism of dry cows fed diets differing in cation-anion difference. AB - Dietary cation-anion difference was defined as the summation of the milliequivalents of Na and K minus the sum of the milliequivalents of Cl and S per kilogram of DM. Twelve Holstein cows were used in a crossover experiment to compare the effects of changing the cation-anion difference of a diet based on haylage. Two cation-anion differences, 481.8 and 327.2 meq/kg, were compared. Increased dietary cation-anion difference had no significant effects on BW or intake and digestibility of DM, ADF, NDF, and N. The diet with a cation-anion difference of 481 meq/kg of DM increased apparent absorption of water and urine volume. Fecal excretion of Na and absorption and urinary excretion of S were increased by a cation-anion difference of 327 meq/kg of DM. Although blood concentrations were unaffected, lower dietary cation-anion difference reduced concentrations of H+ and HCO3- in urine and total urinary excretion of HCO3-. Plasma volume, packed cell volume, glomerular filtration rate, and effective renal plasma flow were unaffected by diet. Small changes in dietary cation-anion differences, even within the positive range, affected acid-base status and water metabolism of dry pregnant cows without affecting renal function or blood volume. PMID- 7782519 TI - Productive life evaluations: calculation, accuracy, and economic value. AB - A preliminary national evaluation of productive life was computed from records of 11 million Holsteins. Data were a mixture of projected and completed months in milk by 7 yr of age. Data were analyzed with the animal model programs currently used for yield traits. Genetic trend for productive life was positive as a correlated response to past selection for yield and type traits. Phenotypic trend was slightly negative. Active AI bulls had PTA that ranged from -1.7 to +4.3 mo and mean reliability of 56%; 3-yr-old cows had mean reliability of 29%. Yield and type PTA were almost uncorrelated with productive life PTA for active AI bulls but had positive correlations (.25 to .36) for all bulls born since 1980. An index that combines yield and productive life PTA with relative weights 2.5:1 can increase economic progress by up to 4%. Nearly identical progress can result from an index that combines yield and productive life adjusted for yield. Multitrait evaluations might produce higher reliabilities for productive life by inclusion of correlated traits measured earlier in life such as yield, type, and somatic cell score. PMID- 7782520 TI - Multiple-trait prediction of transmitting abilities for herd life and estimation of economic weights using relative net income adjusted for opportunity cost. AB - Genetic and phenotypic (co)variances among linear type traits, final score, first lactation milk and fat yield, and 84-mo totals for longevity, relative net income, and relative net income adjusted for opportunity cost of postponed replacement were estimated with a multiple-trait sire model. Data were from 433,116 cows in herds participating in the classification program for conformation traits of the Holstein Association of America. Yield information from all cows in classified herds indicated that classified cows are not a random sample. Heritability of net income adjusted for opportunity cost was higher, .17, than unadjusted net income, .12, but the genetic correlation between the estimates of net income was high, .97. Adjusted net income also had high genetic correlations with first lactation milk yield, .80; fat yield, .60; and dairy form, .48. Heritability of longevity (months in milk to 84 mo) was .06. Adjustment of net income for opportunity cost lowered the genetic correlation with longevity from .84 to .70. Evaluation of lifetime merit using traits measured during first lactation with economic weights developed using adjusted net income was more accurate than indirect prediction of longevity; the approximate reliability of a first-crop AI sire for lifetime merit was .65 compared with .42 for longevity. PMID- 7782522 TI - A simulation study of selection methods to improve mastitis resistance of dairy cows. AB - Mastitis problems were assumed to decrease profitability of dairy cows through milk price, treatment cost, and involuntary culling cost. Milk price decreased through a stepwise function of SCC (actual French conditions). A continuous latent variate was supposed to trigger other costs through appropriate thresholds. The relative weights for one genetic standard deviation in the selection objective were 1, -.07, and -.14 for yield, SCC, and mastitis liability, respectively. Annual genetic gains were predicted for a conventional breeding scheme using statistical parameters from the literature. Selection on yield and log SCC, with or without mastitis culling rate, increased genetic gains for the overall profitability of .7 or .9%, respectively, compared with selection on yield only. Increases of log SCC and mastitis problems because of selection were substantially reduced (40 to 60%). Consequences from constraint of the genetic trend for mastitis liability to zero depended on the method used to assess mastitis problems. Use of log SCC had a significant and variable negative impact (-8.9 to -36% according to parameters) on overall efficiency compared with the relevant unconstrained selection. Simultaneous use of log SCC and culling rate had a moderate effect (-4.9 to -7.4%) on overall efficiency compared with that from unconstrained selection. PMID- 7782521 TI - Comparison of lipid composition of milk from half-Danish Jersey cows and United States Jersey cows. AB - We studied differences in lipid composition of milk from Jersey cows with US sires and from Jersey cows with Danish sires. Milk samples were obtained on DHIA test day from 32 cows with Danish sires and 32 herdmates with US sires in two herds. The Jerseys with US sires were paired with those with Danish sires by parity and stage of lactation. Mean percentage of milk fat was 5.7%, for Jerseys with Danish sires and 4.8% for Jerseys with US sires. Total fat per day was the same (.91 kg) for both groups. Detailed analysis of milk lipids indicated that lipid composition of milk was similar for cows with US sires and those with Danish sires. However, milk from Jerseys with Danish sires contained more free cholesterol than milk from Jerseys with US sires, 17.5 versus 14.3 +/- .6 mg/dl. The proportion of polyunsaturated fatty acids was greater for milk from Jerseys with US sires than for milk from Jerseys with Danish sires (2.3 vs. 2.1%). Although lipid composition of milk from both groups was generally similar, the milk of Jersey cows with Danish sires had higher concentrations of free cholesterol and lower proportions of polyunsaturated fatty acids, both of which are possible negative factors for health of consumers. PMID- 7782523 TI - Effects of interrelationships of production and reproduction on net returns in Florida. AB - Economic aspects of reductions in reproductive efficiency associated with increased production of milk and fat were evaluated for Holsteins and Jerseys in Florida during warm and cool seasons. Net returns from sire selection for increased production were examined with and without incorporation of such negative effects. The economic framework is the application of risk analysis in portfolio selection to selection of dairy sires. Estimates of effects of production on reproduction were from an earlier study of 4293 Holstein and 2143 Jersey cows in first lactation on 14 Florida dairy farms in warm and cool seasons. The scenario represented the typically low reproductive efficiency of cows, especially Holsteins, during summer in Florida, although some statistics used represented US values. Least squares estimates of net returns after adjustment for reproductive losses showed major reductions in net returns for both breeds for both seasons, for example, $28 to $30/yr per lactation, representing 47 to 53% of predicted net returns for Holsteins and 27 to 31% for Jerseys. The results also suggested that increased use of young sires, which results generally in higher conception rates and lower semen costs, might be justified in tropical and subtropical areas, particularly during hot seasons. PMID- 7782524 TI - Initial stages in the development of valid criteria for the replacement of amalgam restorations. AB - OBJECTIVES: Replacement amalgam restorations account for the largest single cost in the General Dental Services in Scotland. There is little practical advice available to practitioners on the maintenance and replacement of amalgam restorations. A distance learning package is being prepared for distribution to general dental practitioners in Scotland and this paper describes the initial stages in the development of the policy statements for the proposed package. METHODS: In the first stage proposals are being developed by a panel of dental academics using a modified Delphi technique. This technique is designed to produce a consensus view. Seventeen statements have been set out by the expert group. RESULTS AND CONCLUSIONS: While agreement was rapidly reached that 'ditching' of amalgam restoration margins did not justify their replacement and that repair was preferable to total replacement, some difficulty was experienced in arriving at a consensus view on the correct management of 'white spot' lesions at restoration margins and dentinal staining adjacent to amalgam restorations. The next stage in the development will be to present these statements to a selected panel of general dental practitioners and to develop their consensus view of the proposals, again using the Delphi technique. PMID- 7782526 TI - Elderly people's adaptability to complete denture therapy: usability of a geriatric behaviour-rating scale as a predictor. AB - Accurately predicting prognosis of complete denture therapy requires a reasonable estimation of the ability of a patient to adapt. The aim of the current study was to test the usability of a geriatric behaviour-rating scale (BOP) as a predictor of elderly people's ability to adapt after complete denture therapy. Ninety-five complete denture-wearing residents of four nursing homes for somatically handicapped patients were randomly divided into two groups, 48 test subjects for whom replacement dentures were prepared and 47 test subjects whose current dentures were improved on. The results of these treatments were evaluated by comparing the scores on the so-called 'scale of appreciation' (complaints of and (dis)satisfaction with complete dentures) prior to and at 2 and 6 months post treatment. Univariate correlations were computed between the scores on the 'scale of appreciation' or the differences in scores at the three evaluation-moments and the foremost BOP-subscale (BOP1, infirmity) and some factors that were considered to be of influence on the process of adaptation. The BOP1 was the only factor showing a significant correlation with the 'scale of appreciation' at 2 months posttreatment; this suggests that little infirmity was connected with a low value of complaints of and dissatisfaction with complete dentures or a positive alteration of this value. It is concluded that the BOP1 can be a useful predictor of complete denture therapy in this group of elderly people. A relationship between elderly people's adaptability to complete denture therapy and the BOP or any other geriatric behaviour-rating scale could be possible. PMID- 7782525 TI - A clinical study of pulsed Nd: YAG laser-induced pulpal analgesia. AB - The pulsed Nd: YAG laser is advocated as an alternative means of providing analgesia during routine dental procedures. Since the evidence to support this claim is mainly anecdotal, a clinical trial was carried out using an electric pulp tester (EPT) to measure the extent and duration of any analgesic effect induced by pulsed Nd: YAG laser treatment. A double-blind crossover experiment involving laser and sham treatments was used on 21 subjects. A small (3.6 arbitrary units) but statistically significant increase was observed in the mean responses measured 5 min after laser treatment with 113 mJ pulses at 15 pulses s 1 (pps) for 3 min. The pain thresholds returned to baseline values after 60 min. No statistically significant changes in threshold were found with the sham treatment. The order in which laser and sham treatment was received made no difference to the results. PMID- 7782527 TI - Assessment of tooth wear in an ageing population. AB - A random sample of 2222 adults aged 45 years and over was taken from the age/sex registers of two general medical practices in Newcastle upon Tyne, and asked to take part in a dental health survey. A total of 1002 individuals agreed to take part and were visited in their homes. Five hundred and eighty-six subjects were dentate and able to undergo an assessment of tooth wear using the Tooth Wear Index (TWI). Increasing wear with increasing age was observed for all cervical and occlusal/incisal tooth surfaces. Occlusal/incisal surfaces displayed some of the highest mean wear scores, especially in the older age cohorts. With the exception of lingual surfaces of maxillary anterior teeth, no significant variation in tooth wear with age was noted for buccal or lingual surfaces. Greater mean wear scores were observed among males than females, but there was little variation between subjects of different social class backgrounds. The threshold levels of wear suggested for use with the TWI may require modification for use among elderly populations. PMID- 7782529 TI - Bacterial adhesion to dental amalgam and three resin composites. AB - OBJECTIVES: The ability of three oral bacteria to adhere to hydrophobic amalgam (water contact angle 60 degrees) and hydrophobic resin composites (Prisma-AP.H 56 degrees. Herculite XRV 82 degrees and Z100 89 degrees) was compared using an in vitro assay. METHODS AND RESULTS: Following preincubation of the materials with human saliva, X-ray photoelectron spectroscopy showed the surfaces to adsorb carbon and nitrogen-containing compounds in a conditioning film that appeared to block the detection of Na and others in 2100 resin. Hg and Ag in amalgam, Si and Zn in Prisma AP.H resin and Ag and Na in Herculite resin. The precoating of the substrata by a proteinaceous conditioning film led to decreased binding of viable cells of Streptococcus sanguis CH3, Streptococcus salivarius HB and Actinomyces viscosus WG as compared with the adhesion to bare composites. With and without salivary coating, there was a correlation between increased bacterial hydrophobicity and increased retention on the substrata. However, there was no statistical difference in binding to the amalgam compared with the resin composites. In vitro studies showed that the bacteria autoaggregated in the presence of saliva. CONCLUSION: The results indicate the potential ability of normal oral flora to colonize resin composite. PMID- 7782528 TI - An in vitro assessment of tooth preparation for porcelain veneer restorations. AB - OBJECTIVES: This in vitro study aimed to examine the depth of preparation and incidence of dentine exposure resulting from the use of a 'freehand' technique to prepare maxillary central incisors for porcelain veneers. METHODS: Twenty-two maxillary central incisors were selected. Prior to preparation an index of the labial surface of each tooth was recorded and the tooth secured in a jig to permit accurate relocation. Two operators each prepared 11 teeth aiming to reduce the labial thickness evenly by 0.5 mm. Low viscosity silicone impression material was then placed on the index and the teeth relocated into the jig. Upon removal, this material was sectioned in the cervical, middle and incisal thirds of the tooth and its thickness measured using a toolmaker's microscope. The teeth were acid etched and also stained with a dentine dye to identify any area of dentine exposed during preparation. RESULTS: Significant differences (P < 0.001) in the depth of preparation at different sites, with least reduction in the mid-incisal region, were found. Greater reduction was found at the cervical and proximal margins with areas of dentine exposed at those sites in the majority of teeth. CONCLUSIONS: In view of the incidence and position of dentine exposure found in this study, the use of a dentine bonding system during the placement of porcelain veneers would appear essential when employing a 'freehand' preparation technique. PMID- 7782530 TI - Antibacterial activity of MDPB polymer incorporated in dental resin. AB - OBJECTIVES: Previously, we have reported that dental composite incorporating the new monomer methacryloyloxydodecylpyridinium bromide (MDB) showed no release of antibacterial components after being cured but still exhibited antibacterial activity against Streptococcus mutants on its surface. In this study, in order to elucidate the mechanism of the antibacterial effect of immobilized MDPB, the bactericidal activity of MDPB polymer in water-soluble and -insoluble form was investigated, and the effect of MDPB polymer on bacterial attachment was estimated. METHODS: Solutions of homo-polymer of MDPB and co-polymer of MDPB with acrylamide were prepared and the viability of seven major oral streptococci was determined after incubation with each polymer solution. For the estimation of bactericidal activity of insolubilized MDPB polymer, bacteria were kept in contact with cured unfilled Bis-GMA-based resin discs with or without MDPB, and the recovery of viable cells was measured. Attachment of streptococci to cured resin discs with or without MDPB was also compared using radiolabelled bacteria. RESULTS: Water-soluble homo-polymer of MDPB and co-polymer with acrylamide showed bactericidal activity against oral streptococci. However, cured resin incorporating MDPB, which is in water-insoluble form, had little bactericidal activity. Attachment of streptococci, including species which are early colonizers in dental plaque formation, to the cured resin containing MDPB was significantly less than to the control without MDPB. CONCLUSIONS: These results indicate that the bactericidal activity of MDPB polymer is reduced after immobilization, but MDPB on the surface of a resin-based material still shows a bacteriostatic effect and antiadhesion property against oral streptococci. PMID- 7782532 TI - Recruitment issues: errors of omission in dental research. PMID- 7782531 TI - Influence of light intensity on two restorative systems. AB - OBJECTIVES: High intensity curing lights are recommended almost universally on the basis of immediate curing depth measurements. Although this single factor is well documented, the influence of light intensity on other parameters has not been investigated extensively. METHODS: Two restorative systems were examined with two light intensities in regard to four properties; polymerization shrinkage (density method), flexural modulus and strength (ISO 4049), hardness profiles after post-cure (Vickers), and marginal adaptation in dentine cavities (quantitative margin analysis). RESULTS: The variation in light intensity did not significantly affect curing contraction or post-cure hardness profiles to a depth of 4.5 mm for either resin composite. Significant differences were found in flexural modulus with both restoratives; only one material demonstrated a light intensity-related influence on flexural strength. Marginal gap formation increased in each bonding agent/resin composite pair with increased light intensity. CONCLUSION: In clinically relevant layer thicknesses, curing a resin composite with a higher intensity light may demonstrate significant disadvantages due to increased shrinkage stress. PMID- 7782533 TI - Multiple-outcomes meta-analysis of treatments for periodontal disease. AB - The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure. When clinical trials use two or more outcome measures (such as PD and AL), investigators ordinarily analyze each outcome separately. When the correlations are incorporated among the outcomes, a meta-analysis can use generalized-least squares (GLS) regression to analyze multiple outcomes jointly. We applied the GLS multiple-outcomes model in a meta-analysis of 5 trials comparing surgical and non surgical periodontal treatments, each assessing the outcomes PD and AL one year after treatment. The clinical conclusions are similar to those reported earlier, but our estimates of the relative benefits of surgical and non-surgical treatment should be more accurate, because the GLS method takes into account correlation between AL and PD. When correlations between the two outcomes rise, as they do with increasing severity of disease, the GLS estimates depart from those derived from separate analyses of PD and AL. PMID- 7782534 TI - Monoclonal antibodies against a high-molecular-weight agglutinin block adherence to experimental pellicles on hydroxyapatite and aggregation of Streptococcus mutans. AB - High-molecular-weight (HMW) glycoproteins, agglutinins, in parotid saliva induce the aggregation of S. mutans and mediate binding of the bacteria to saliva-coated hydroxyapatite (SHA). Two types of monoclonal antibodies (mAb) directed against, respectively, protein and carbohydrate epitopes on the agglutinin have been reported to inhibit the aggregation of S. mutans. In this study, the mAbs were tested for their ability to block aggregation and adherence to SHA of S. mutans serotype c mediated by parotid, submaxillary, and whole saliva from three subjects. Both types of antibody inhibited the adherence and aggregation in a dose-dependent manner. However, individual variations were noted for the effects of the antibodies. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS PAGE) and subsequent immunoblotting with the antibodies revealed a > 300 kDa agglutinin component in all types of saliva and in the proteins desorbed from SHA. The degree of staining of this component in immunoblots of the salivas and the desorbates seemed to be paralleled by the rates of aggregation and adherence, respectively. Thus, our results indicate that the adherence to SHA as well as the aggregation of S. mutans serotype c is primarily mediated by structurally related, HMW glycoproteins in parotid, submaxillary, and whole saliva. PMID- 7782535 TI - Salivary PAF levels correlate with the severity of periodontal inflammation. AB - Platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, has been previously identified in inflamed gingival tissues and gingival crevicular fluid. However, the role of PAF in oral pathobiology remains unknown. The purpose of the present study was to evaluate the relationship between salivary PAF levels and the severity of periodontal inflammation. PAF activity in lipid extracts of whole (mixed) saliva collected from 69 untreated subjects immediately prior to routine oral evaluation was determined by platelet bioassay. Significant positive correlations were observed between the level of PAF in saliva and measures of periodontal inflammation, i.e., the percentage of periodontal probing depths greater than 4 mm, the number of periodontal bleeding sites, and the number of histologically identified polymorphonuclear neutrophilic leukocytes (PMN) in saliva. Moreover, when subjects were subdivided into groups on the basis of periodontal probing depths, a significant correlation was observed between salivary PAF levels and the extent of periodontal disease, i.e., PAF levels in saliva progressively increased from the healthiest group to the most severely affected group. Thus, salivary PAF levels correlate with the severity of periodontal inflammation. These results support the hypothesis that this pro-inflammatory phospholipid autacoid may participate in the pathogenesis of periodontal tissue injury and disease. PMID- 7782536 TI - Differential expression of IL-1 beta, TNF-alpha, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes. AB - Macrophages respond to bacterial lipopolysaccharides (LPS) and activate several host defense functions through production of mediators. However, it is not clear whether the degree of macrophage responsiveness to different sources of LPS is equivalent to or varies with the source of LPS. Therefore, in this report, we examined the extent of the human monocyte response to LPS derived from two oral pathogens, Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg). Additionally, due to its well-established ability to activate monocytes, we used LPS from Escherichia coli (Ec). Human monocytes, when activated with a specific source of LPS, exhibited rapid expression of mRNA for IL-1 beta, TNF alpha, and IL-8, which was followed by IL-6, as measured by RNA-PCR. Moreover, the expression of mRNA for these cytokines was followed by cytokine synthesis. Monocytes from the same subject, when activated with LPS from Pg, Aa, or Ec expressed quantitatively different levels of mRNA and proteins for all four cytokines. A given LPS induced either high or low expression of the battery of cytokines tested, indicating that the expression of these pro-inflammatory cytokines may be regulated by a single or a cluster of gene(s). However, no apparent differences in the time course of mRNA expression for these cytokines were observed in response to any of the LPS tested. Furthermore, the relative ability of the different sources of LPS to induce mRNA for cytokines varied throughout a wide range of LPS concentrations. This suggests that differences exist in the sensitivity of monocytes to a specific LPS, rather than in the kinetics of the secretory process itself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782537 TI - Enhanced cytokine production and collagen synthesis of gingival fibroblasts from patients with denture fibromatosis. AB - The mechanisms of denture-induced gingival hypertrophy remain to be explored. Since fibroblast proliferation and bone resorption characterize this disorder, the possible involvement of cytokines was investigated. Gingival fibroblasts were obtained from six patients with denture fibromatosis (Den-Fb) and six healthy persons (Nor-Fb). Cells were compared for proliferation, collagen synthesis, and cytokine production. Incorporation of [3H]thymidine (TdR) was increased in 3 Den Fb and 3 Nor-Fb lines in the presence of interleukin-1-beta (IL-1 beta) (10 U/mL) and tumor necrosis factor-alpha (TNF-alpha) (from 10 to 100 U/mL). Proline incorporation in Den-Fb was higher than that in Nor-Fb, and the mean collagen synthesis level in Den-Fb was significantly higher than that in Nor-Fb. Although there was no difference between the up-regulation of protein synthesis in Den-Fb and Nor-Fb induced by IL-1 beta or TNF-alpha, the receptors for these cytokines were expressed at higher levels in cell lines which exhibited higher protein synthesis. Between Nor-Fb and Den-Fb, there was no difference in the generation of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-6 (IL 6). However, most Den-Fb produced more GM-CSF and IL-6 in the presence of TNF alpha. Enhancement of IL-6 generation by GM-CSF was also more prominent in Den Fb. GM-CSF and IL-6 were synergistically generated after co-culture of the fibroblasts with gingival keratinocytes. GM-CSF and IL-6 generation of Den-Fb was markedly enhanced by co-culture of Den-Fb with peripheral blood mononuclear cells (PBMC), especially PBMC from patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782538 TI - Effects of fluoride on the calcium phosphate precipitation method for dentinal tubule occlusion. AB - Use of the calcium phosphate precipitation (CPP) method makes possible the occlusion of dentinal tubules to approximately 10 to 15 microns from the dentinal surface, and thus shows good potential for the treatment of dentin hypersensitivity. The precipitate formed in the dentinal tubules by the CPP method is, however, not apatite [HAP; Ca10(PO4)6(OH)2], a component of tooth and bone, but dicalcium phosphate dihydrate (DCPD; CaHPO4.2H2O). Since fluoride enhances the conversion of DCPD to HAP, we evaluated the effects of fluoride on the texture of the precipitate formed by the CPP method and on its capacity to occlude dentinal tubules in this in vitro study. CPP solution (1.0 mol/L CaHPO4.2H2O dissolved in 2.0 mol/L H3PO4) was applied to a dentin disk and was subsequently neutralized with a post-treatment solution (1 mol/L NaOH, from 0 to 0.1 mol/L NaF). Scanning electron microscopy revealed that the precipitate occluded dentinal tubules to a depth of approximately 10 to 15 microns from the dentinal surface, regardless of the NaF concentration (from 0 to 0.1 mol/L) in the post-treatment solution. Also, dentin permeability was reduced to 15% by the CPP treatment regardless of the NaF concentration. The Ca/P molar ratio of the precipitate, measured by x-ray micro-analysis, was higher (1.25 +/- 0.04) in the presence of NaF than in its absence (1.03 +/- 0.01). For further identification of the precipitate formed in the dentinal tubules, the same procedure was used in glass tubes (diameter, 1 mm), so that a larger amount of precipitate would be obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782539 TI - Light deposition in dental hard tissue and simulated thermal response. AB - Near-IR (approximately 1 micron) lasers are presently used for a variety of intra oral applications including dental hard tissue ablation, although the light intensity distribution and subsequent heating of the hard tissue are still poorly understood. This paper presents a detailed numerical study of the scattered light intensity distribution along with the corresponding predicted thermal response. The calculations are based on recently published scattering and absorption data for dental hard tissue around 1 micron. Our simulations indicate strongly enhanced energy deposition and concomitant heating near the dentino-enamel junction (DEJ), mainly due to the higher absorption in dentin. We predict from 10 to 20 times higher internal temperatures near the DEJ compared with the surface. For example, for 50-ms pulses of 5-J energy on a 3-mm-diameter spot (approximately 1 kW/cm2 or approximately 50 J/cm2), one can expect internal temperatures near the DEJ in excess of 100 degrees C. Elevated temperatures are predicted to extend far into the dentin, endangering the vitality of the pulp several millimeters below the surface. Our results are compared with published experimental data taken under similar conditions and are found to be in good general agreement. The results of this study do not contradict recently reported ablation of dentin with Nd:YAG laser radiation by contact fiber probes. In this case, the irradiation intensities are 3 to 4 orders of magnitude higher, so plasma formation and plasma shielding of the interior of the tooth are likely. PMID- 7782541 TI - Combined estimation of mercury species released from amalgam. AB - Amalgam fillings constitute, after food, the main source of exposure to mercury for the general population. Banning amalgam would incur huge costs for additional dental treatment. An evaluation of potential health risks must be based on the mercury dose released from fillings. In this study, dose is estimated by a new procedure of mercury speciation which elutes the released elemental and inorganic mercury with solvents of differing polarity. We tested the procedure by incubating spherical amalgam pellets in a mixture of light paraffin oil and saline (0.9% NaCl). Release of mercury into paraffin and saline was linear in relation to both amalgam surface area and exposure time. Measurements with this method were then extended to a group of 21 amalgam-bearing volunteers. The absorbed dose averaged 4.8 micrograms/day compared with 3.7 measured conventionally in intra-oral air from the same persons. With both methods, the dose was significantly correlated to the number of amalgam-covered tooth surfaces. This dose, combined with the nearly equal mercury uptake from food, is far below the acceptable daily intake limit. PMID- 7782540 TI - Tensile properties of resin-infiltrated demineralized human dentin. AB - The ability of adhesive resins to restore the physical properties of demineralized dentin has not been well-documented. The unfilled resins that are used for adhesion have relatively low moduli of elasticity and limited ability to increase dentin stiffness, although they may increase the ultimate tensile strength of dentin. This study tested the hypothesis that resin infiltration of demineralized dentin can restore its tensile properties to those of mineralized dentin. Small (ca. 0.5 mm thick x 0.5 mm wide) specimens of demineralized human dentin were infiltrated with one of five different dentin bonding resins over many hours, to determine how these resins altered the tensile properties of dentin. Tensile stress and strain were measured in these and control (mineralized and demineralized) specimens until their ultimate failure. The results indicate that some adhesive resins, after infiltrating demineralized dentin, can restore and even exceed the ultimate tensile strength of mineralized dentin. These resins increased the modulus of elasticity of resin-infiltrated dentin to values equal to or greater than those of the resins but far below those of mineralized dentin. Although the conditions in this experiment were far removed from the manufacturer's recommendations or clinical practice, the results support the potential of resin infiltration for reinforcing dentin. PMID- 7782542 TI - Preparation and characterization of cyclopolymerizable resin formulations. AB - An amine-catalyzed reaction between acrylates and formaldehyde has been used to convert mono-acrylates to difunctional monomers and di-acrylates to multifunctional oligomers by linking the acrylic double bonds together in 1,6 diene pairs. The resulting monomers and oligomers undergo efficient cyclopolymerization to high conversion with significantly less shrinkage than normally found for acrylates. In this study, a convenient single-step process was used with mixtures of mono- and di-acrylate starting materials to produce a series of resins with potential for effective cyclopolymerization. Incremental changes in the ethyl acrylate (EA) to ethoxylated bisphenol A diacrylate (EBPAD) ratio directly supplied cyclopolymerizable resins with a broad range of viscosities and product distributions. Those resins produced from reaction mixtures rich in EA have low viscosities because of high diluent monomer contents and limited oligomerization of EBPAD due to end-cap formation. Resin viscosity and average molecular weight of the oligomeric component of the resin were inversely related to the amount of EA used in the reaction. Through the choice of reactants and their ratio, this simple technique has the potential to provide cyclopolymerizable resins for use in a variety of dental polymer applications. PMID- 7782543 TI - Critical Issues in Dental Clinical Research. Proceeding of a symposium. Seattle, Washington, March 10, 1994. PMID- 7782546 TI - The Institute of Medicine's report on dental education. PMID- 7782544 TI - Critical issues in periodontal research. AB - The purpose of this paper is to highlight briefly the major achievements and the remaining critical issues in the areas of epidemiology, microbiology, pathogenesis, diagnosis, and therapy. Periodontitis affects a relatively small proportion of study populations in the United States and other countries. Prevalence may be decreasing, but that remains to be seen. The identity and characteristics of susceptible individuals and groups are not known, and risk indicators for severe disease are only beginning to be identified. A very large number of different microbial species has been implicated in the etiology. It seems unlikely that all of these are essential participants. Essential participants need to be identified and better characterized. Whether putative pathogens are members of the commensal flora or exogenous species that must be transmitted is unclear. The relationship between the presence of a pathogenic flora and disease status is obscure. Pathogenic bacterial species are essential, but insufficient to cause disease. A susceptible host and local environmental factors--for example, elevated iron concentration--may be necessary for disease to occur. Many clonal types may not be virulent, and numbers greater than certain threshold levels appear to be necessary. The pathways by which bone and connective tissues of the periodontium are destroyed are sufficiently understood to permit development of therapies aimed at their modification. Examples are the use of vaccines, topical application of anti-inflammatory drugs, and use of chemically modified tetracyclines. PMID- 7782545 TI - Validity of diagnostic and monitoring tests used for temporomandibular disorders. AB - Currently, diagnosis of temporomandibular disorders (TMD) depends on a comprehensive history and physical examination, supplemented, when indicated, by images of hard and soft tissues. However, there are electronic diagnostic devices being marketed to acquire other measures described as relevant to TMD and to use these for diagnosis of TMD and for monitoring the effects of treatment. This paper reviews the capacity of several devices to measure these variables accurately and reliably and to assess the theoretical basis of each of these tests. Diagnostic ability was established, when possible, according to the commonly accepted measures of sensitivity, specificity, and positive predictive values. It was found that many tests lack theoretical validity, that measurement validity tends to be poor, and that diagnostic ability can be even worse than chance, because of a high percentage of false-positive diagnoses. Based on these findings, the use of these instruments in clinical practice is inappropriate at this time and may lead to the treatment of large numbers of subjects who have no disorder. PMID- 7782547 TI - Dental education institutions must respond to the Institute of Medicine report. PMID- 7782548 TI - Educating dentists for the twenty-first century. PMID- 7782550 TI - Managed care in dental schools. PMID- 7782549 TI - Market forces driving health care reform. PMID- 7782551 TI - Designing preclinical instruction of psychomotor skills (IV)--Instructional engineering: evaluation phase. PMID- 7782552 TI - Mandatory consent to treatment by students in dental education: legal and policy considerations. PMID- 7782553 TI - Survey of clinic fees and clinic revenue--summary report, 1993-94. AB - Figure 4 shows the mean unadjusted revenue-per-student by program type. Advanced Education General Dentistry programs had the highest revenue-per-student this year and in two of the three previous years. Oral and Maxillofacial Surgery programs generated the second highest mean amount of clinic revenue-per-student, followed by General Practice Residencies, Orthodontic programs, and Prosthodontic programs. Pediatric Dentistry, Endodontics, and Periodontics programs also had similar mean revenues-per-student. The smallest revenues-per-student were generated by D.D.S./D.M.D. and dental hygiene programs. These data should be interpreted with care. A review of the information for each program shows that there are significant variations in these data from school to school. These variations could be caused by different accounting procedures as well as differences in program size and location. Consequently, these data are best viewed in general terms. PMID- 7782555 TI - Dose-response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models. AB - To determine the maximum allowable intake limits for chronic dietary exposure to cadmium (Cd), the dose-response relationship between total Cd intake and prevalence of renal dysfunction was examined using general linear models considering the effect of age as a confounder. The target population comprised 1850 Cd-exposed and 294 non-exposed inhabitants of Ishikawa, Japan. They were divided into 96 subgroups by sex, age (four categories) cadmium concentrations in rice (three categories) and length of residence (four categories). As indicators of the cadmium-induced renal dysfunction, glucose, total protein, amino nitrogen, beta 2-microglobulin and metallothionein in urine were employed. General linear models were fitted statistically to the relationship among prevalence of renal dysfunction, sex, age and total Cd intake. Prevalence of abnormal urinary findings other than glucosuria had significant associations with total Cd intake. When total Cd intake corresponding to the mean prevalence of each abnormal urinary finding in the non-exposed subjects was calculated using general linear models, total Cd intakes corresponding to glucosuria, proteinuria, aminoaciduria (men only) and proteinuria with glucosuria were determined to be ca. 2.2-3.8 g and those corresponding to prevalence of metallothioneinuria were calculated as ca. 1.5-2.6 g. The low-molecular-weight protein in urine was confirmed to be a more sensitive indicator of renal dysfunction, and these total Cd intake values were close to those calculated previously by simple regression analysis, suggesting them to be reasonable values as the maximum allowable intake of Cd. PMID- 7782554 TI - Evaluation of the toxicity of several heavy metals by a fluorescent bacterial bioassay. AB - This new bioassay determined the toxicity of chemical compounds dissolved in water by measuring the degree of inhibition of the ultraviolet light-stimulated fluorescence of Escherichia coli in a culture medium in which 4 methylumbelliferyl beta-D-glucuronide was the only carbon source. Inhibition produced by one of five heavy-metal salts (Cd2+, Cr6+, Hg2+, Pb2+ or Zn2+) was the end-point and comparison standard to determine the EC50 and minimum effective concentration (MEC) that produced a decrease of E. coli growth rate, increased doubling time and percentage inhibition and reduced numbers of generations; all these values were derived from the fluorescence signals. Only Cr6+ and Hg2+ at two concentrations (0.25 and 0.5 mg l-1) almost completely inhibited this E. coli strain. All toxicant concentrations tested produced at least partial inhibitions of growth; Cr6+, Hg2+ and Cd2+, in that order, were most toxic, and Pb2+ the least. Zn2+ gave higher EC50 values at 3 h of incubation than at 4 h. The method was simple, rapid and inexpensive and would permit a large number of samples to be tested quickly. PMID- 7782557 TI - High fat diet and liver damage induced by biliary obstruction in the rat. AB - There is a great body of evidence linking a high fat diet with the formation of gallstones. However, the effect of fat per se on obstructive liver damage (not involving gallstone formation) has not been assessed. The aim of this work was to study the effect of a high fat diet on liver damage induced by bile duct ligation in rats. Male 21-day-old Wistar rats were divided into two groups: group 1 received standard Purina chow diet 5001 containing 4.5% fat, group 2 received Purina chow diet 5001 enriched with 33% pork fat. Animals were allowed food and water ad libitum for 5 weeks. Obstructive jaundice was induced by double ligation and division of the common bile duct. The animals were sacrificed 1 week after biliary obstruction. Control animals were sham operated. Serum bilirubins and alkaline phosphatase, gamma-glutamyl transpeptidase and glutamic pyruvic transminase enzyme activities increased by biliary obstruction. Glycogen content decreased in the bile duct-ligated rats. These effects were more important in the group fed a 33% fat diet. Our results show that a high animal fat diet increases liver damage in experimental biliary obstruction in rats. Owing to our experimental design (bile duct ligation), the effect of a high fat diet cannot be attributed to an increase in the formation of gallstones but a direct effect must be considered. The mechanism by which fat augmented liver damage can be associated with an increase of total bile content and its toxicity. PMID- 7782556 TI - Two-generation reproduction toxicity study with isopropanol in rats. AB - A two-generation reproduction toxicity study was conducted in rats with isopropanol. Thirty rats of each sex per group (P1) were dosed once daily by oral gavage with 0, 100, 500 or 1000 mg isopropanol kg-1 for at least 10 weeks prior to mating. Parental animals were mated within groups for up to 3 weeks. Parental females were dosed during mating, gestation and lactation; parental males were dosed during mating through delivery of their last litter sired. The P2 adults were selected from the F1 litters and were dosed for 10-13 weeks before mating to produce a single litter. Findings in the parental animals included increased lactation body weight gain in the mid- and high-dose females, increased liver and kidney weights in the mid- and high-dose groups of both sexes and centrilobular hepatocyte hypertrophy in some P2 males. There was also accumulation of hyaline droplets and other microscopic findings in the kidneys from the mid- and high dose P1 males and from all treated groups of the P2 males. Increased mortality was observed in the high-dose F1 offspring during the early postnatal period, although no other clinical signs of toxicity were observed in the offspring of either generation. In addition, offspring body weight was reduced during the early postnatal period in the high-dose F1 males and in the high-dose F2 pups of both sexes. Eighteen out of 70 F1 weanlings in the 1000 mg kg-1 group died or were euthanized prior to P2 selection. No treatment-related post-mortem findings were observed in the offspring from either generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782558 TI - Decrease in hepatotoxicity by lead exposure is not explained by its mitogenic response. AB - The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450. PMID- 7782559 TI - Reduction of erythema in hairless guinea pigs after cutaneous sulfur mustard vapor exposure by pretreatment with niacinamide, promethazine and indomethacin. AB - Erythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD-induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin and promethazine used alone or in all possible combinations on the degree of erythema and histopathologic skin damage after HD exposure in HGP. Niacinamide (750 mg kg-1, i.p.), promethazine (12.5 mg kg-1, i.m.) or indomethacin (4 mg kg-1, p.o.) used singly or in combination was given as a 30-min pretreatment before an 8-min HD vapor cup skin exposure. Using a combination pretreatment of niacinamide, promethazine and indomethacin, erythema was reduced at 4 (91%) and 6 (55%) h, but not 24 h after HD. The incidence of histopathological skin changes (microvesicles, follicular involvement, epidermal necrosis, intracellular edema and pustular epidermatitis) 24 h after HD was not reduced. This study indicates that HD-induced erythema may result from several different mechanisms, including inflammation, histamine release and DNA damage. It is suggested that two phases of inflammation may occur: an early phase sensitive to antihistamines and non-steroidal antiinflammatory drugs and a late phase of extensive cell damage that was not sensitive to these drug pretreatments. PMID- 7782560 TI - Acute renal and hepatic effects induced by 3-haloanilines in the Fischer 344 rat. AB - Haloanilines are commonly used as chemical intermediates in the manufacture of a wide range of products. The purpose of this study was to examine the in vivo nephrotoxic and hepatotoxic potentials of the 3-haloanilines. The in vitro effects of the 3-haloanilines on renal function were also examined. In the in vivo experiments, male Fischer 344 rats (four rats/group) were administered a single intraperitoneal (i.p.) injection of an aniline hydrochloride (1.0 or 1.25 mmol kg-1) or vehicle. Renal and hepatic function were monitored at 24 and/or 48 h post-treatment. None of the 3-haloanilines were potent nephrotoxicants at either dose level. The greatest effects on renal function were observed following administration of 3-chloroaniline at a dose of 1.25 mmol kg-1 (oliguria, glucosuria, hematuria, decreased p-aminohippurate accumulation by renal cortical slices and increased blood urea nitrogen concentration). 3-Chloroaniline also was the only aniline compound to increase plasma ALT/GPT activity at 48 h. In the in vitro experiments, the ability of an aniline (10(-5) - 10(-3) M) to decrease organic ion accumulation in renal cortical slices from untreated rats was examined. The decreasing order of in vitro nephrotoxic potential was 3 iodoaniline > 3-bromoaniline > 3-chloroaniline > aniline > 3-fluoroaniline. These results indicate that the 3-haloanilines are not potent nephrotoxicants or hepatotoxicants at sublethal doses. In addition, the reasons why the 3 haloanilines have different orders of nephrotoxic potential in vivo and in vitro are not clear at this time. PMID- 7782561 TI - An in vitro method for determination of tissue partition coefficients of non volatile chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and estradiol. AB - The development of an in vitro vial equilibration technique for determining tissue and liquid partition coefficients for non-volatile chemicals is described. Radiolabeled chemical dissolved in propylene carbonate is equilibrated with tissues or liquid at 37 degrees C in a vial system. The solvent must be essentially immiscible with the test material. The amount of chemical movement to the tissue or liquid is compared to an appropriate reference vial, and tissue or liquid:solvent partition coefficients are calculated. Tissue:solvent values divided by blood:solvent values provide tissue:blood partition coefficients required for developing physiologically based pharmacokinetic models for chemicals. These models are useful for estimating internal tissue doses to assess human risk from exposure to chemicals. Partition coefficients for various rat tissues, 0.9% saline solution and olive oil were determined in this study for radiolabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and for the less fat soluble compound, estradiol. The TCDD tissue:propylene carbonate partition coefficients were found to be: blood, 0.091; fat, 17.02; liver, 0.419; brain, 0.632; kidney, 0.305; muscle, 0.408. For estradiol, the tissue:propylene carbonate partition coefficients were: blood, 0.286; fat, 0.169; liver, 1.032; brain, 0.554. The TCDD results compared well with values reported and estimated from a more protracted in vivo approach. Thus, this current technique offers a simpler and time-saving alternative to in vivo approaches for determining the partition coefficients of non-volatile compounds. PMID- 7782562 TI - Isopropanol: acute vapor inhalation neurotoxicity study in rats. AB - Five groups of 25 Fischer 344 rats of each sex were exposed for 6 h to isopropanol vapor at 0, 500, 1500, 5000 or 10,000 ppm. Behavioral observations for 10 rats of each sex were made prior to and 1, 6, and 24 h after exposure. Motor activity was evaluated for 15 rats of each sex prior to and immediately following exposure. Exposure to isopropanol caused a spectrum of transient effects indicative of narcosis at 10,000 ppm and sedation at 5000 ppm. Prostration or severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular function, hypothermia and loss of reflex function were observed 1 and 6 h after exposure to 10,000 ppm isopropanol vapor. Similar, but less severe, alterations were observed in animals in the 5000 ppm exposure group 1 h after exposure. Exposure concentration-related decreases in motor activity were observed in males and females in the 5000 and 10,000 ppm groups and slight decreases in motor activity were observed in males in the 1500 ppm group. Animals in the 1500 and 5000 ppm exposure groups recovered from these motor activity effects within 5 h. Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration-related narcosis and/or sedation at concentrations of 5000 and 10,000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no-observed-effect level (NOEL) for this was 500 ppm isopropanol. PMID- 7782563 TI - Epidermal carcinogenesis studies of EDS liquids. AB - A series of liquids representing different potential design options or operating configurations for the EDS direct coal liquefaction process* were evaluated for skin cancer potential. All of the samples that contained substantial amounts of material boiling above 370 degrees C were active dermal carcinogens; tumor yields were near 100% and median times to tumor development generally ranged from 30 to 40 weeks. Two liquids that boiled below ca. 200 degrees C were tested and each produced one squamous cell tumor. These data suggested that high-boiling-point, coal-derived liquids are likely to be relatively potent dermal carcinogens; whereas low-boiling-point liquids do not possess significant carcinogenic potential. Based on a comparison of the carcinogenic potency data, liquids produced by the EDS process apparently do not present a significantly greater dermal carcinogenic hazard than other coal-derived materials of similar boiling range. PMID- 7782564 TI - Mechanism of citrinin-induced dysfunction of mitochondria. III. Effects on renal cortical and liver mitochondrial swelling. AB - The effects of the mycotoxin citrinin on renal cortical and liver mitochondrial swelling were studied. Citrinin decreases the rate of swelling induced by the valinomycin-K+ complex, suggesting that the mycotoxin interferes with the mitochondrial membrane fluidity. Citrinin promotes reduction of the amplitude of swelling in the presence of Na+ ions. This alteration reflects interference with complex I of the respiratory chain and ATP synthase complex activity without disarranging the inner mitochondrial membrane, in view of the fact that the shrinkage was not affected. The effect increases with citrinin concentration. Renal tissue is more susceptible than hepatic tissue. PMID- 7782565 TI - Pharmacokinetics of benzophenone-3 after oral exposure in male rats. AB - Benzophenone-3 (BZ-3) is one of the UV-absorbing agents that has been used in industry and medicine for more than 30 years. Millions of consumers are exposed to benzophenones on a daily basis owing to the widespread use of these compounds in many of the products on the market, such as lipsticks, hair sprays, hair dyes, shampoo and detergent bars and sunscreen lotions. This study was performed to investigate the pharmacokinetics of BZ-3 after oral administration at 100 mg kg-1 body weight in male Sprague-Dawley rats. Absorption from the gastrointestinal tract was rapid because BZ-3 was detected in blood 5 min after administration. The peak plasma concentration (Cmax) was 25.6 +/- 4.6 micrograms ml-1 and the time of occurrence (tmax) was 3.0 +/- 0.4 h. The half-life of absorption of BZ-3 was 0.71 h. The elimination pattern was biphasic with alpha and beta half-lives of elimination of 0.88 and 15.90 h, respectively. The results of this study indicate the presence of strong binding between the plasma protein and BZ-3. Tissue distribution studies at 6 h indicate that the liver contained the highest concentration of free (58.9 +/- 23.8 micrograms) and total (free+bound or conjugated) BZ-3 (2087 +/- 60.1 micrograms), followed by kidney and testes, respectively. Urine and feces analysis indicate that urine was the major route of excretion, followed by feces. Further analysis of urine samples also indicates that conjugation of BZ-3 with glucuronic acid was the major systemic elimination route for the compound. PMID- 7782566 TI - Micturitional disturbance in myotonic dystrophy. AB - Micturitional disturbance has attracted little attention in myotonic dystrophy, but detailed micturitional histories revealed that two out of six patients (33%) had micturitional symptoms. One had difficulty urinating and the other had urinary frequency, urgency and stress incontinence. Urodynamic studies were performed in all patients and the results were as follows: Two had low maximum urethral closure pressure, two had large and three had small bladder capacities, one had detrusor hyperreflexia and one had atonic cystometrogram. Urethral sphincter electromyography revealed a decreased bulbocavernosus reflex in one, and an absent anal reflex in two. Motor unit analysis of external sphincter was performed with one patient and showed polyphasic potentials. Dystrophic changes of the lower urinary tract muscles, as well as supranuclear type of pelvic nerve dysfunction, could cause micturitional disturbance in patients with myotonic dystrophy. PMID- 7782567 TI - Time-course and frequency dependence of sympathetic stimulation-evoked inhibition of vagal effects at the sinus node. AB - Vagally-induced chronotropic responses have been shown to be inhibited after the termination of sympathetic stimulation. We sought to characterize the onset and time-course of the sympathetically evoked inhibition of vagal effects by measuring vagally induced chronotropic responses during concomitant sympathetic stimulation. In anesthetized dogs we recorded lead II of the electrocardiogram, arterial pressure and cardiac cycle length. In 7 dogs, the vagi were stimulated for 15 s every minute before, during and after 10-min trains of sympathetic stimulation. The sympathetic stimulation was applied at frequencies of 0.5, 1, 2, 5 and 10 Hz. During the 1, 2 and 5-Hz trains of sympathetic stimulation, the vagally induced changes in cycle length diminished progressively and thus, were less (P < 0.001) at 3, 5 and 10 min compared with 1 min into the sympathetic stimulation. The magnitude of the attenuation of vagal effects on cycle length depended (P < 0.001) on the frequency of sympathetic stimulation. To determine the role of alpha- and beta-adrenergic receptors, we measured vagally-induced changes in cycle length during 5-min trains of sympathetic stimulation (1, 2, 5, 10 Hz) in the presence and absence of phentolamine and propranolol (n = 6). Both before and after combined alpha- and beta-adrenergic receptor blockade, the vagally-induced changes in cycle length decreased (P < 0.03) progressively during the 1, 2, 5 and 10-Hz trains of sympathetic stimulation and the magnitude of the inhibition depended (P < 0.002) on the frequency of sympathetic stimulation. These data show that the effects of short trains of vagal stimulation on cardiac cycle length are inhibited progressively during continuous trains of sympathetic stimulation before and after combined alpha- and beta-adrenergic receptor blockade. Thus, substances other than norepinephrine may contribute to the inhibition of cardiac vagal effects that occurs during a continuous train of sympathetic stimulation. PMID- 7782568 TI - Arrangement of dendrites and morphological characteristics of sympathetic preganglionic neurones projecting to the superior cervical ganglion and adrenal medulla in adult cat. AB - Sympathetic preganglionic neurones (SPN) projecting to the superior cervical ganglion (SCG) and adrenal medulla (AM) in the adult cat were retrogradely labelled with cholera B horseradish peroxidase (CBHRP). Labelled neurones were found in 4 sub-nuclei: the nucleus intermediolateralis thoracolumbalis pars principalis (ILp), the nucleus intermediolateralis pars funicularis (ILf), the nucleus intercalatus spinalis (IC) and the nucleus pars paraependymatis (ICpe). The majority of SPN were found in the ILp (75%). Each group of target specified SPN had a different segmental distribution. SCG-SPN between cervical 8 (C8) and thoracic 6 (T6) and AM-SPN between thoracic 3 (T3) and lumbar 2 (L2). Fusiform and round bodied neurones were the most common shapes found, a third longitudinal type was occasionally found. SCG and AM-SPN exhibited a dense rostrocaudal dendritic projection extending along the length of the ILp. There was also a lateral projection into the ILf and a medial one projecting towards the central canal. This dendritic arrangement gave the ILp the appearance of being an 'open nucleus'. The dendrites branched at their distal ends and all along their lengths swellings could be seen. It was concluded that contrary to previous descriptions the arrangement of SPN in the adult cat is not too dissimilar to that in the adult rat. PMID- 7782569 TI - A study of sympathetic preganglionic neuronal activity in a neonatal rat brainstem-spinal cord preparation. AB - Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonatal rat brainstem-spinal cord preparation. Neurones were identified as SPNs as they were: (i) activated at constant latencies (2-10 ms) following stimulation of the ventral root, which indicated antidromic activation and (ii) recorded at sites located either in the intermediolateral cell column or the intercalated nucleus of the thoracic spinal cord. Over one-third of the neurones (n = 17) recorded displayed ongoing activity with firing frequencies of 0.3-5 Hz. Of the neurones analyzed only one showed a very obvious phasic firing pattern. Dorsal root stimulation evoked firing in 16 of 26 SPNs recorded from the same spinal segment (6 of 10 with ongoing activity). The types of responses observed varied between neurones. The excitation of all neurones was characterised by a response occurring at a latency of 6-50 ms. In addition, SPNs in 'spinalised' preparations (n = 2) responded with latencies of 10-40 ms, similar to those observed in the intact preparation. The latencies of responses in SPNs were longer and more variable than those observed in ventral horn motor neurones. This indicates that a spinal polysynaptic pathway was involved in mediating these responses. In 7 SPNs dorsal root stimulation also elicited longer latency responses which were observed up to 1000 ms after stimulation. These responses may involve activation of bulbospinal and/or propriospinal pathways. These results show that the neonatal rat brainstem-spinal cord preparation is viable for studying SPNs and that dorsal root-SPN reflexes are intact. PMID- 7782570 TI - Effects of the autonomic ganglion blocking agent hexamethonium on vasodilator responses mediated by the parasympathetic ganglion on the chorda tympani pathway of the cat. AB - We investigated the pharmacological properties of a parasympathetic ganglion (a chorda tympani ganglion) that mediates vasodilator responses in the lower lip induced by electrical stimulation of the distal cut end of the chorda tympani or facial nerve root of the cat. These responses were suppressed by prior treatment with the autonomic ganglion blocking agent hexamethonium. We compared the effects of three doses of hexamethonium (1, 3 and 10 mg/kg, i.v.) on the chorda tympani ganglion with their effects on three large ganglia; the otic, submandibular and pterygopalatine ganglia that mediate vasodilator responses. Experiments were conducted on 20 cats weighing 1-3 kg which had been anesthetized with a mixture of urethane (100 mg/kg, i.v.) and chloralose (50 mg/kg, i.v.) then artificially ventilated (pancuronium bromide 0.2 mg/kg per h, i.v.). The chorda tympani ganglion's sensitivity to hexamethonium was similar to that of the otic ganglion but differed from the sensitivities of submandibular and pterygopalatine ganglia. We speculate that transmission through the chorda tympani ganglion is pharmacologically similar to the otic ganglion, although its precise location has yet to be determined. PMID- 7782571 TI - Quantitative assessment of the autonomic nervous system activities during atropine-induced bradycardia by heart rate spectral analysis. AB - Using power spectral analysis of heart rate fluctuation, autonomic nervous system activities in bradycardia appearing in the initial phase of atropine administration were evaluated quantitatively in 16 healthy females. Atropine sulfate (10 micrograms/kg), diluted in 100 ml of 0.9% NaCl solution, was intravenously infused at a rate of 0.5 micrograms/kg per min. Electrocardiograms were sampled for 4 min for later analysis before and 0, 5, 10, 15 and 20 min after initiation of atropine infusion. Powers of low (LFC, 0.05-0.15 Hz) and high frequency (HFC, 0.15-0.4 Hz) components in the power spectrum of R-R interval variations, and the LFC/HFC ratio were determined at each sampling point. HFC power at 0-4 min increased from 1.11 +/- 0.18 ms2 (mean) of baseline value to 1.37 +/- 0.19 ms2 (P < 0.05). The next 5-9-min value of 1.48 +/- 0.14 ms2 was the maximum, and the amount of atropine infused by 9 min was 4.5 micrograms/kg. The HFC powers following this point decreased. The 20-24-min value after 10 micrograms/kg atropine decreased to 0.21 +/- 0.03 ms2 (P < 0.01), which was lower than the previous 15-19-min value of 0.36 +/- 0.04 ms2 (P < 0.01). The LFC/HFC ratios showed no significant change for the initial 9 min of the atropine infusion. However, these ratios at 15-19 min and 20-24 min were increased from 0.50 +/- 0.04 (mean) of baseline value to 0.75 +/- 0.09 and 0.81 +/- 0.09, respectively (P < 0.01). A transient vagotonic state after atropine administration, followed by the well-known vagolytic state, was quantitatively detected by non-invasive spectral analysis of heart-rate fluctuation. PMID- 7782572 TI - Secondary amyloidosis with severe autonomic dysfunctions. AB - A 46-year-old male underwent hemodialysis because of progressed glomerulo nephritis. Since he suffered from severe diarrhea during the course of the illness, both gastric and colon biopsies were performed. Significant amyloid deposition was recognized in the submucosal layer of these specimen. This amyloid was positive for anti-AA-protein antibody staining and soluble in KMnO4 solution, indicating secondary induced amyloid. Despite of absence of orthostatic hypotension, examinations revealed extreme reduction in tears and salivary secretion, anhidrosis, a decrease in the coefficiency of variation of the cardiographic R-R interval, and a decrease in the accumulation of [123I]meta iodobenzylguanidine (MIBG) in the heart, suggesting that severe glandular and visceral autonomic dysfunctions had occurred in the patient. PMID- 7782573 TI - Gait training and falls in the elderly. AB - 1. Patients with gait and balance disorder, as measured by the Tinetti Mobility Scale, can benefit from physical therapist-assisted gait training. 2. Score in the Tinetti Mobility Scale negatively correlates with the number of recurrences of falls. 3. The nurse's role includes identification of those who are at risk for falls, assessment of their response to training in preventing recurrence of falls, and the effect of training in their mobility and independence. PMID- 7782574 TI - Hospitalized elders: the difficulties families encounter. AB - 1. Family members encountered difficulties when an elder was hospitalized for an acute episode of a chronic illness. 2. It is important for nurses to recognize the kinds of difficulties that family members experience and develop strategies to alleviate them. 3. Failure to include family members in discharge planning can place elders at risk for readmission to the hospital. PMID- 7782575 TI - Non-equilibrium systems theory: some applications for gerontological nursing practice. AB - 1. In terms of NEST, aging can be understood as a process of formative change toward increasing disorder and order in form, pattern, or structure. The person moves toward greater complexity through self-organization processes. 2. Over time, self-organization processes result in increasingly unique perceptions and behavior. As an older person becomes more unique, he or she becomes more different from other older persons. 3. Self-organization processes are an appropriate focus of concern for nursing when NEST is used as a practice framework. The nurse tries to understand older persons' behaviors as outcomes of self-organization processes (attempts to bring order out of disorder). PMID- 7782577 TI - Using validation techniques to improve communication with cognitively impaired older adults. AB - 1. Nurses working with confused older adults in clinical settings need improved communication techniques. 2. Reality orientation is commonly used in nursing homes with disoriented persons; experienced nurses, however, often find it meets with withdrawal, vegetation or increasing hostility. 3. Validation strategies are communication techniques which are specifically matched to a particular stage of confusion. 4. When validation techniques are appropriately matched to confusional stage the effectiveness of the intervention can be significantly improved. PMID- 7782576 TI - Perceptions of acute care nurses in the use of restraints. AB - 1. Staff nurses continue to use physical restraints in well-intended efforts to protect patients from potential harm despite the overwhelming evidence of negative consequences from this practice. The use of physical restraints remains an unresolved clinical practice issue. 2. This stratified, random sample demonstrated that LPNs consistently attached greater importance to the use of restraints than either RNs or Managers, suggesting that the educational level of nurses may have an impact on the continued use of physical restraints. 3. The survey further demonstrates that nurses are aware of many alternatives to restraint use. The authors suggest that alternatives may not be widely used because the measures are often not considered practical. PMID- 7782578 TI - A worthy project. PMID- 7782579 TI - Gerontological nursing issues and demands beyond the year 2005. PMID- 7782580 TI - [Psychological effects of embryonal reduction. From the decision making to 4 months after delivery]. AB - The psychological effect of reducing the number of embryons was studied prospectively in two Paris hospitals. All women who had multifetal pregnancy reduction (n = 18) were contacted for interviews just after the operation, during pregnancy, and four months after delivery. The decision to reduce the number of embryons was painful and led to a guilty feeling. After operation, nearly one half of the women suffered psychologically. To justify their decision, and contain their emotions, the women spoke of the problems related to having triplets and, most importantly, the medical arguements explained by the physician. Medical counselling is thus essential to help this couples at the time of the operation. The pregnancy period is almost always a period of calm for these women. Nevertheless, four months after delivery, 5 women expressed a psychological malaise related to the reduction, and 2 women refused to continue the study because they did not want to revive their suffering. This study shows that psychological problems are of major importance after multifetal pregnancy reduction and can occur several months after delivery. These negative conclusions should however be examined in light of the consequences if reduction had not been performed. PMID- 7782582 TI - [Post-coital vesicovaginal fistula after treatment for cervical cancer. Cure by prolonged bladder drainage after epiploplasty failure. Two cases]. AB - Post-coitus vagina-bladder fistulas are rarely encountered although they may be favoured by radiosurgical treatment for cervical cancer. Treatment is particularly difficult. When initial epiploplasty is a failure, most authors recommend an ileocytoplasty with ad integrum reconstruction of the vaginal and of bladder function. PMID- 7782581 TI - [Consequences of laser CO2 treatment of cervical intraepithelial neoplasias on the anatomic and functional integrity of the cervix]. AB - OBJECTIVES: Retrospective study to analyse objectively the effectiveness and anatomic and functional consequences for the cervix of conservative CO2 laser treatment for cervical intraepithelial neoplasia. PATIENTS AND METHODS: Analysis of therapeutic effectiveness and anatomic consequences of 1,114 treated patients followed at our colpolaparotomy surgery clinic for cervical dysplasia since 1987. Evaluation of function consequences by comparison with a group of patients who delivered after laser CO2 therapy for dysplasia (n = 56) and a group of control patients (n = 95) with a similar type of dysplasia after delivery and no treatment. The clinical course of the pregnancy and delivery were compared between the groups in search for risk of prematurity. RESULTS: Good preservation of cervical anatomy was achieved after a rigorous treatment protocol only applicable with CO2 laser. The preservation of the junctional zone facilitated diagnosis of recurrence. The risk of prematurity was low. Therapy was successful in 93.4% of the cases. CONCLUSION: The choice of conservative therapy is essential, not only when the patient desires a pregnancy but also in others since preserved anatomy facilitates diagnosis of recurrence. This findings implicate the need for an unagressive energy source and also accepting the early diagnosis and treatment. PMID- 7782583 TI - [Borderline ovarian tumors. A review and 11 cases]. AB - OBJECTIVE: To clarify and classify the still debated diagnostic and prognostic elements of borderline tumours of the ovary and analyze the data obtained in our series. AIM: Develop an adapted management scheme, integrating relatively good prognosis and known or suspected factors of poor prognosis. SIEGE: Department of Gynaecology-Obstetrics, Hotel-Dieu (CHU) Rennes, France. SUBJECTS: Eleven patients with borderline tumour of the ovary diagnosed and managed over the last 5 years. RESULTS: Current morphology and macroscopy examinations of the tumour do not provide data capable of predicting malignancy. The borderline nature of the tumour is not a histological diagnosis. The problems encountered lead to a search for new techniques such as digitalized nuclear morphology. Some progress has been made in classifying prognosis factors. Other than stage, important factors appear to be age, histological type, mitotic index, atypical cells and invasive peritoneal implants. Management decisions depend on prognosis factors but should especially take into account parity. Methods include cystectomy and total hysterectomy with annexectomy. Evaluation of chemotherapy and radiotherapy is still to preliminary. CONCLUSION: The slow clinical course, allowing good mid term prognosis, is still the best reason for a moderated therapeutic approach relying on conservative or more aggressive surgery alone. PMID- 7782584 TI - [Ovarian hydatic cyst. 7 cases]. AB - Seven cases with echinococcal infection of the ovary, including 3 on both sides, were collected at the Salah Azaiz Institute of Tunis during a period of 23 years. This localisation is rare, even in an endemic country. The aetiology and pathogenesis of this affection may give rise to many different clinical signs, problems with pre-operative diagnosis. It is important to follow up these cases after operation in order to sport recurrences. The objective of surgical treatment is to achieve cure of both the hydatic cyst of the ovary and the primitive cyst simultaneously. Following this treatment, two difficulties may arise: the first one is preoperative rupture of the cyst; the second concerns fertility in these young women after two-sided salpingo-oophorectomy. Finally, when a pelvic cyst is observed systematic hydatic serology must be performed. PMID- 7782586 TI - [Complete non-obstetrical uterine inversion]. AB - A rare case of a gynaecologic uterine inversion is reported emphasizing on the exceptional character of the gynecologic uterine inversion and the pathogenic problems which are tackled. Gynaecologic inversion results from a tumor implanted on fundus of the uterus or from the essential atrophy of suspension ligaments of the uterus. Treatment depends on the anatomic type and the stage. PMID- 7782585 TI - [Uterine hemangiopericytomas. Two case reports]. AB - The diagnosis of uterine haemangiopericytoma is still a matter of debate. The existence of haemangiopericytoma must be proven on the basis of classical histology, ultrastructure histology and immunohistochemical analyses. The diagnosis, even when apparently sure, must nevertheless be proven. We described two cases emphasizing the clinical and laboratory features of uterine haemangiopericytoma. Progress in nuclear magnetic resonance imaging, ultrastructural analysis and immunohistochemistry should help in confirming the diagnosis of haemangiopericytoma. Highly vascular leiomyoma or low malignity grade leiomyosarcoma have been mistakenly identified as haemangiopericytoma. PMID- 7782587 TI - [Breast adenomyoepithelioma. A case report and review of the literature]. AB - Adenomyoepithelioma of the breast is a rare tumor which exceptionally degenerates, requiring treatment and large exeresis. We report a new case and review the literature. PMID- 7782589 TI - [Parvovirus B19 infection and pregnancy]. AB - Parvovirus B19 was identified in 1975. It causes infections megalerythemia in adults associated with skin eruptions and joint pain (about 50% of the adult population is immunized). The risk of contamination in case of an epidemia is high in school teachers and school personnel. In 1984, the parvovirus B19 was implicated as the cause of fetal anasarca. The risk of transplacental contamination is estimated at 33% in case of maternal infection. Pregnant women with parvovirus B19 infection and confirmed serology should have an echography every 15 days. Fetal anasarca can be complicated by in utero fetal death related to erythroid stem-cell anaemia. The diagnosis of fetal infection is based on PCR techniques on fetal blood. Symptomatic antenatal treatment with in utero transfusion was proposed as early as 1988. This method does not however appear to be necessary in all cases as the outcome in several reports of untreated fetuses was delivery of a normal child. There is the possibility of myocardial damage caused by parvovirus B19 which would make in utero transfusion difficult and limit its beneficial effect. Finally associated thrombopenia is often severe and increased fetal risk. PMID- 7782588 TI - [Prenatal diagnosis of nuchal edemas and cystic hygromas of the neck. 49 cases]. AB - OBJECTIVES: Determine the pathogenesis of fetal nuchal oedema and cystic hygromas of the neck and establish prenatal prognosis factors. METHODS: Retrospective study of 49 cases including 35 early diagnoses (10 to 14 weeks gestation) and 14 late diagnosis (after 15 weeks). Chorial villosity biopsy was performed for fetal karyotype. RESULTS: The global rate of genetic or chromosomic abnormalities in the fetuses was 47%. The fetuses with nuchal associated with other echographic anomalies had a high risk of chromosomic aberrations (80%). Fetuses with nuchal oedema alone during the first trimester had a higher risk of trisomy 21 proportionally with the age of the mother and paradoxically no trisomy 21 was found in women under 30 years of age. When early nuchal oedema regressed spontaneously in an euploid fetus, echographic surveillance can be proposed to detect possible polymalformation syndromes discovered late. Cystic hygromas of the neck were diagnosed from 15 weeks gestation and were always pathologic. CONCLUSION: Interpreting nuchal images in the fetus must take into account the echographic term at discovery and its isolated or associated nature. Further studies are needed to determine indications for chorial villosity biopsy in mothers under 30 with a fetus with isolated nuchal oedema which regresses spontaneously during the first trimester. PMID- 7782590 TI - [Steinert's disease and pregnancy. A case report and recent literature]. AB - Steinert's disease or myotonic dystrophy is a heredo-degenerative neuroendocrinal dystrophy. It is an autosomal dominant disorder. The arising of a congenital myotonic dystrophy of one of the new-born children of the maternity hospital enabled to diagnose the Steinert's disease of his mother. A review of the international literature enabled us to recall its interactions with pregnancy. There is an aggravation of myotonia and multiple obstetric complications such as miscarriage, premature onset of labor, polyhydramnios, stillbirth, difficulties during the evacuation, atonic postpartum hemorrhage, anesthetic-accidents. The congenital variant of myotonic dystrophy (6 to 30% of the cases) is a severe disease with a high mortality. It is only seen in the offspring of mothers who themselves have myotonic dystrophy. The myotonic dystrophy gene has been isolated and the mutation-causing myotonic dystrophy was found to result from a series of trinucleotide (CTG) repeats located in the 3' untranslated region of the gene. The direct diagnosis is henceforth possible both on the fetus and parents. Steinert's disease and its association with pregnancy are rare, especially when the affected parent has hypogonadism. The diagnosis of the congenital form is difficult because of the mother is unaware of the disorder. Family and personal history may give hints: hydramnios, appearance delay and reduced fetal movements, and the association at birth of generalized hypotonia with neonatal respiratory distress. PMID- 7782591 TI - [Manual rotation of vertex presentations in posterior occipital-iliac or transverse position. Technique and value]. AB - OBJECTIVE: Evaluate of the usefulness of manual rotation of occipito-posterior or transverse presentation. DESIGN: One year retrospective study (1991). SETTING: Maternity hospital, Clinique Universitaire Baudelocque. SUBJECTS: All patients during labour having a spontaneous (n = 160) or a manual rotation (n = 368) of an occipito-posterior or occipitotransverse presentation. The manual rotation could be indicated for a fetal distress, a protracted first stage of labour or prophylactically. INTERVENTION: Manual rotation as described by Tarnier, was performed at least at 7 cm cervical dilatation. MAIN OUTCOME MEASURES: Success rate of manual rotation, cesarean section rate, maternal, fetal and neonatal complications. PMID- 7782592 TI - [Placenta membranacea. Review of the literature, a case report]. AB - Placenta membranacea or placenta diffusa is a rare abnormality in which all or most of fetal membranes remain covered by chorionic villi, because the chorion has failed to differenciate into chorion laeve and chorion frondosum. This condition is associated with recurrent antepartum bleeding, abortion in the second trimester of the pregnancy, preterm delivery, fetal death, intra-uterine growth retardation, post partum haemorrhage and placental retention. In this paper, we report our first case of placenta membranacea. A 30-year-old black woman, gravida 3, para 1, was admitted at 23 weeks of gestation for vaginal bleeding. She was placed on complete bed rest. Ultrasonographic examination showed a placenta covering the anterior and posterior uterine walls and the internal cervical os. At 28 weeks and 34 weeks of gestation, ultrasound examination showed the same findings: total placenta previa covering the entire uterine wall and presenting many lacuna. At 38 weeks, she underwent a cesarean section. The placenta adhered firmly to the myometrium. Because the attempts to remove the placenta was unsuccessful, it was performed a total hysterectomy. The total blood loss was 7000 ml. Anatomo-pathologic examination of the placenta led do the diagnosis of placenta membranea, total previa and increta. In the literature, 35 cases of placenta membranacea have been reported; of these, there are ten cases associated with total hysterectomy. PMID- 7782593 TI - [Indications and prognosis of cesarean sections at the Dakar University Hospital Center]. AB - From 1st January 1992 to 30 June 1994, 8489 delivered at the Dakar University Hospital. Among them, there were 953 cesarean sections, i.e. 11.2%. Epidemiological analysis revealed that mean parity was 2 for a mean age of 26 years. 22% of the women had a clinically perceptible pelvic problem. The indications for cesarean section were divided into 3 groups: mandatory operations (feto-pelvic disproportion, haemorrhagic placenta praevia, dystocia): 41.4%; prudent operations (long-awaited infant, fetal suffering, breech presentation, cicatricial uterus): 50%; and necessary operations (maternal disease, especially hypertension): 8.6%. There was a high postoperative mortality (1.4%) and major morbidity, especially infection (10%). Neonatal prognosis was also poor with a 14% early neonatal mortality. These findings reflect the major problems facing obstetricians in Senegal and Subsaharian Africa. Improved prognosis necessarily will involve better organization of our health systems allowing easier access to life-saving cesarean section for our rural populations. PMID- 7782594 TI - [Validation trial of a neonatal prophylactic antibiotic protocol in the delivery room]. AB - Maternofetal infection occurs in 1 to 10 of every 1,000 newborns. Prognosis is poor and an extremely rapid the clinical course is sometimes observed. The situation suggests that widespread use of antibiotics and more than 90% of the newborns receiving antibiotics are not infected. A prospective study based on simple, recognized criteria predictive of maternal-fetal infection was conducted in 3,392 deliveries to evaluate the effect of an antibiotic prophylaxy protocol. Specificity, sensitivity, positive and negative predictive value were evaluated for each of the eleven criteria retained with the goal of increasing sensitivity and decrease the use of unnecessary antibiotics. Among the 3,392 infants delivered from January 1989 to December 1990, 286 (8.4%) newborns entered the study and were given mezlocillin (150 mg/kg/12 h). This treatment was stopped at 48 hours of life if the infant was not infected. RESULTS. Infection was confirmed in 48 of 3,392 infants (1.4%). All were in the risk group: 48/286 (16.7%). The germs the most often found were group B Streptococcus (n = 16), Escherichia coli (n = 8) and Listeria monocytogenes (n = 3). Nine criteria were well correlated with maternal-fetal infection. The two most important criteria were maternal pyrexia above 39 degrees C and Apgar score below 7 to 5 min (poor neonatal adaptation), with a 99% and 90% and a positive predictive value of 80% and 37% respectively. Inversely, Two criteria were poorly correlated with maternal-fetal infection: labour duration above 12 hours and instrumental extraction (positive predictive value from 10% to 17%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782595 TI - [Programmed autologous transfusion in obstetrics. Blood samples in 100 patients in the last month of pregnancy]. AB - OBJECTIVES: Evaluation (usefulness and safety) of programmed autologous transfusion in obstetrics. SITE. Blood Transfusion Centre, Hopital Louis-Mourier, F 92700 Colombes. PATIENTS: Prospective study of 150 patients for whom blood withdrawal was planned during the last month of pregnancy. Entry criteria were either a risk of haemorrhage or persistent patient request. PROTOCOL: Two withdrawals were planned during the last month of pregnancy at the out-patient clinic at a one-week interval. The autologous units were transfused per-partum in case of haemorrhage and/or post-partum in case of anaemia. RESULTS: One hundred pregnant women entered the protocol (43 had a risk of haemorrhage). Both preplanned withdrawals were made in 60 of these patients. Per-partum transfusions were necessary in only 7 patients including 4/43 with a risk factor (9%) and 3/57 with no risk factor (5%). Post-partum transfusions were made in 22 other patients. Consequently, 117 of the 160 units collected were not used (73%). CONCLUSION: Despite good tolerance (5% incidence) due to the known problems in evaluating the risk of haemorrhage and the small percentage of patients without risk factors who were transfused per-partum, we have decided to reserve this protocol for patients with an authentically identified risk of haemorrhage (placenta praevia, cesarean section, uterine scar tissue). PMID- 7782596 TI - [Practical use of sulprostone in the treatment of hemorrhages during delivery]. AB - OBJECTIVE: To assess intravenous use of sulprostone (Nalador), a prostaglandin E2 analogue, is case of post-partum haemorrhage due to uterine atonia. MATERIALS AND METHODS: A retrospective study on 315 cases of post-partum haemorrhage (PPH) from 1st January 1990 to 31st December 1992 in Baudelocque maternity. In 91 cases of PPH due to uterine atonia, usual oxytocin drugs were not sufficient and intravenous sulprostone was used. Characteristics of the patients, mode of sulprostone administration, side effects and treatment failures are reported. RESULTS: One or two dose of 500 micrograms were sufficient in 71% cases. Mean perfusion rate was 8.3 micrograms/mn. Success of treatment was 89% with few side effects (5.5%). No serious complication due to sulprostone was observed. Risk of treatment failure was 8.3 times greater when the delay between diagnosis of uterine atonia and sulprostone administration was more than 30 mn. CONCLUSION: Prostaglandins treatment, and particularly sulprostone, could be used more frequently and earlier in case of PPH due to uterine atonia. Further controlled studies are necessary to know if they should be used as a first line treatment instead of oxytocin in this indication. PMID- 7782597 TI - [Streptococcal meningitis: a possible complication of prolonged use of an intrauterine device]. PMID- 7782598 TI - Does iron deficiency raise the seizure threshold? AB - To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure. A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01). The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use. Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04). This association was even stronger when adjusted for differences in family history. None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04). Iron deficiency may protect against the development of febrile seizures. PMID- 7782599 TI - Fryns syndrome: neurologic findings in a survivor. AB - Fryns syndrome, a multiple congenital anomaly syndrome associated with diaphragmatic defects, craniofacial dysmorphism, distal digital hypoplasia, and neurologic abnormalities, was first described in 1979. This autosomal recessive disorder is usually associated with stillbirth or death immediately after birth. Detailed neurologic findings in the third survivor beyond the neonatal period are reported, and neurologic abnormalities in other cases are reviewed. Initially, hypotonia, areflexia, and weakness were seen. Myoclonus developed immediately after birth and was well controlled with high-dose valproate. Electroencephalography revealed slowing and irregular paroxysmal discharges with spikes and sharp waves that disappeared with time and treatment. Magnetic resonance imaging demonstrated partial agenesis of the corpus callosum, a Dandy Walker malformation, and progressive cerebral and brainstem atrophy. This syndrome should be considered in patients with unusual facial features and digital abnormalities associated with frequent early myoclonus. PMID- 7782600 TI - Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy. AB - A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration. PMID- 7782602 TI - Brain weight and sudden infant death syndrome. AB - Increased brain weights have been reported in the literature to occur among infants who have died from sudden infant death syndrome, suggesting that cerebral edema might play a role in the cause of death among these children. We have compared brain weights from children between the ages of 1 week and 1 year, autopsied between 1980 and 1992. One group consisted of 125 victims of sudden infant death syndrome and the other of 38 children who had died with a diagnosis other than the sudden infant death syndrome. Brain weights from both groups exceeded the 50th percentile in previously published reference material. We were unable to show any significant differences between the groups in either the ratio between observed and expected brain weights or the ratio between brain weight and body weight. We conclude that there is no evidence for the notion that victims of sudden infant death syndrome have an increased brain weight. Other authors (in previous studies) may have overlooked the low overall weight at gestational age of prematurely born children while collecting data for reference levels. A revision of the figures seems to be necessary. PMID- 7782601 TI - Ataxia-oculomotor apraxia syndrome. AB - Ataxia-oculomotor apraxia is a distinct entity first comprehensively described in 1988. The features include early childhood onset of ataxia and oculomotor apraxia, mimicking ataxia telangiectasia but without the extraneurologic findings of ataxia telangiectasia. We add to the clinical description of the ataxia oculomotor apraxia syndrome by reporting eight patients, ages 2 to 15 years, from four families, suggesting autosomal recessive inheritance, with the longest follow-up over 6 years. After initial gait deterioration, all had a nonprogressive course. We have postulated that ataxia-oculomotor apraxia should be established as a separate disease from ataxia telangiectasia or its variants not only by clinical history, examination findings, and course, but primarily by the biologic markers of normal chromosome breakage and radiation sensitivity studies. We found no increased chromosome breakage in the four patients studied and intermediate sensitivity to chronic ionizing radiation of cultured skin fibroblasts on the three patients studied. Family studies revealed an intermediate radiosensitivity from two patients, their asymptomatic parents, and a sister. The lack of chromosome breakage strongly separates ataxia-oculomotor apraxia from ataxia telangiectasia. The radiation sensitivity studies are compatible with two possibilities: (1) symptomatic ataxia telangiectasia heterozygotes, but this would be highly unusual because the degree of clinical involvement in the ataxia-oculomotor apraxia patients is not mild, as would be expected if they were heterozygotes and (2) a separable disease entity, which is the interpretation we favor. PMID- 7782603 TI - Landau-Kleffner syndrome with continuous spikes and waves during slow-wave sleep. AB - The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782604 TI - The use of felbamate to treat infantile spasms. AB - Based on the initial successful use of felbamate for infantile spasms in an infant with tuberous sclerosis, three additional infants with infantile spasms of different etiologies who had failed conventional therapies were treated with felbamate. Three of the four patients have shown complete resolution of infantile spasms. All responding patients did so within 1 week of starting felbamate. The one treatment failure had an initial reduction of seizure frequency and severity but has not maintained that response long term. Controlled studies are needed to firmly establish that felbamate is both safe and effective for the treatment of infantile spasms. As these cases document, felbamate is currently available for use in infantile spasms, and the frequent conversion of infantile spasms to Lennox-Gastaut syndrome, for which felbamate is approved, makes its use in infantile spasms logical. PMID- 7782605 TI - D-2-hydroxyglutaric aciduria. AB - Hydroxyglutaric aciduria is detected by gas chromatographic-mass spectrometric analysis, and the D and L forms are quantified by chemical ionization with deuterated internal standards. Patients have recently been described who accumulate the D form, and they appear to be quite different from those with the more common L form. Experience is reported with three patients and an animal model with D-2-hydroxyglutaric aciduria. The phenotype appears to include mental retardation, macrocephaly, hypotonia, seizures, and involuntary movements, although neurologic and systemic manifestations of the disorder varied considerably between individual patients, even within the same family. PMID- 7782606 TI - Medical treatment of West syndrome in Japan. AB - Although corticotropin (ACTH) is still the most effective drug for the treatment of West syndrome, a variety of other treatment modalities have been tried because of corticotropin's frequent and sometimes serious side effects. A recent survey on the treatment of this devastating disorder by Japanese child neurologists disclosed different therapeutic approaches from those taken by American or European child neurologists. Most Japanese child neurologists use vitamin B6 as the first agent and corticotropin as the third or second drug. Moreover, the dosage of corticotropin used by them is considerably smaller. Therefore, the current status of medical treatment of West syndrome is reviewed, especially comparing Japan with other countries. PMID- 7782607 TI - The glamour of scientific research. PMID- 7782608 TI - The childhood muscular dystrophies: diseases sharing a common pathogenesis of membrane instability. AB - New observations demonstrate that several childhood forms of muscular dystrophy share a common pathogenesis. In muscle, dystrophin occurs as part of a membrane complex (dystrophin-glycoprotein) linking the cytoskeleton to the basal lamina. In Duchenne muscular dystrophy, dystrophin deficiency disrupts the linkage of the integral glycoproteins of the sarcolemma and leads to muscle fiber necrosis. In severe childhood autosomal recessive muscular dystrophy, a selective deficiency of adhalin (50-kd glycoprotein) also causes dysfunction of the dystrophin glycoprotein complex. Most recently, a form of congenital muscular dystrophy demonstrates deficiency of laminin M (merosin) further demonstrating that sarcolemmal instability results from defects in structural proteins of the basal lamina. Animal models have been identified also demonstrating defects in specific proteins linking the subsarcolemmal cytoskeleton to the extracellular matrix. The mdx mouse has a defect in the gene encoding dystrophin. The cardiomyopathic hamster shows a specific deficiency of adhalin in skeletal muscle. The dy/dy mouse has been found deficient in merosin. These animal models will help researchers to understand their human counterparts and provide a system for testing therapeutic strategies. PMID- 7782609 TI - A clinical approach to the congenital myasthenic syndromes. PMID- 7782610 TI - Containing partisan medical experts. PMID- 7782611 TI - Magnetic resonance imaging for spinal muscular atrophy. PMID- 7782612 TI - Sickle cell disease and stroke. PMID- 7782614 TI - Accuracy of neurologic examination and history in detecting evidence of MRI diagnosed cerebral infarctions in children with sickle cell hemoglobinopathy. AB - We determined the accuracy of neurologic examination and the history of a previous neurologic event in detecting clinical evidence of a magnetic resonance imaging (MRI)-diagnosed cerebral infarction in 30 children with sickle cell hemoglobinopathy. Each patient had an MRI of the brain, neurologic examination, chart review, and psychometric evaluation. Seventeen children (57%) had MRI evidence of cerebral infarction based on demonstration of parenchymal abnormalities in a vascular distribution. Among the 17 children with MRI evidence of cerebral infarction, only 12 (71%) had an abnormal neurologic examination, and 11 (65%) had a history of a prior neurologic event. In contrast, among the 13 children with normal MRIs, 12 (92%) had normal neurologic examinations, and no child had a previous history of a neurologic event. Multiple, bilateral, heterogeneous cerebral infarctions frequently occur without overt neurologic signs or symptoms in children with sickle cell hemoglobinopathy. Previous studies that relied on a focal neurologic examination or a history of a neurologic event to identify cerebral infarctions in patients with sickle cell hemoglobinopathy most likely underrepresented the true frequency of cerebral infarctions in this population. Future prospective studies of cerebral infarctions in children with sickle cell hemoglobinopathy should include MRIs for identification and classification, rather than neurologic examination or clinical history alone. PMID- 7782613 TI - Parasitic infections of the central nervous system in children. Part II: Disseminated infections. AB - In the second segment of this three-part review of parasitic infections of the central nervous system in children, we consider parasitic infections which typically involve various tissues and organs in addition to the brain and spinal cord. Parasites capable of dissemination in immunocompetent hosts are discussed first, and, as in Part I, organisms are grouped according to their predominant geographic location. This is followed by a discussion of the unique aspects of toxoplasmosis, strongyloidiasis and infection with microsporidia in immunocompromised patients, with an emphasis on the central nervous system. PMID- 7782615 TI - A persistent biochemical marker for partially treated meningitis/ventriculitis. AB - Regulation of circulating iron is important in bacterial, yeast, and fungal infections. In the present study, cerebrospinal fluid levels of ferritin, an iron binding protein, were determined in controls and in patients with central nervous system pyogenic and viral infections. Among 441 controls, cerebrospinal fluid ferritin level was higher than 18 ng/mL in two relapsed patients with central nervous system leukemia, 12 with bacteremia or pneumonia, and one with hemorrhagic herpes simplex encephalitis. Cerebrospinal fluid ferritin levels were more than 18 ng/mL in 13 of 63 patients diagnosed with nonhemorrhagic aseptic meningitis/ventriculitis, when defined solely by negative cerebrospinal fluid culture. Conversely, cerebrospinal fluid ferritin exceeded 18 ng/mL in culture proven meningitis (46 of 47 cases) and ventriculitis (five of five cases). Cases of indolent cryptococcus and tuberculous meningitis showed modest increases despite traditional cerebrospinal fluid markers, at times, being normal. Cerebrospinal fluid ferritin levels did not correlate with cerebrospinal fluid neutrophil count, cerebrospinal fluid protein concentration, serum ferritin level, or patient age. In 16 of 19 cases monitored sequentially during ongoing antibiotic treatment, levels remained over 18 ng/mL (average, 15.0 days; range, 1 to 54 days). This observation suggests that obtaining cerebrospinal fluid ferritin levels is helpful whenever traditional laboratory benchmarks normalize, as during acute or chronic antibiotic therapy, or create confusion with positive cultures stemming from sample contamination. PMID- 7782616 TI - Misdiagnosis of appendicitis in nonpregnant women of childbearing age. AB - A retrospective case series was conducted at a teaching hospital with an emergency department (ED) census of 100,000 patients per year to identify the incidence of, and factors associated with, the misdiagnosis of appendicitis in nonpregnant women aged 15 to 45 years. There were 174 nonpregnant women identified with a pathologic diagnosis of appendicitis. Clinical features were then compared between patients misdiagnosed (seen in prior 10 days and given an incorrect diagnosis) and those who were initially diagnosed correctly. The results showed that 33% of the women with appendicitis were initially misdiagnosed. The most common misdiagnoses included pelvic inflammatory disease, gastroenteritis, and urinary infections. Misdiagnosed women more frequently exhibited diffuse and bilateral lower abdominal pain and tenderness, cervical motion, and right adnexal tenderness. Misdiagnosed women also had a lower incidence of right lower quadrant pain and tenderness, and peritoneal signs. In addition, misdiagnosis was associated with an increased incidence of perforation, abscess formation, and an increase in the total length of hospitalization. In conclusion, the incidence of misdiagnosis of appendicitis in women of childbearing age is high. Women who are misdiagnosed have less typical symptoms and physical findings and more frequent abnormal pelvic findings than those who are diagnosed correctly. Emergency physicians should be aware that atypical signs and symptoms are associated with misdiagnosed appendicitis in nonpregnant women of childbearing age. PMID- 7782617 TI - Resolution of caffeine-induced complex dysrhythmia with procainamide therapy. AB - A case report of a 38-year-old male who ingested 20 gm of caffeine is presented. The patient exhibited clinical and laboratory evidence of caffeine toxicity. Cardiac monitoring revealed a chaotic rhythm with variable supraventricular and ventricular dysrhythmias without hemodynamic compromise. Procainamide was used effectively to convert this complex dysrhythmia. The mechanisms, manifestations, and therapy of caffeine toxicity are reviewed. PMID- 7782618 TI - A new approach to emergency department therapy of migraine headache with intravenous haloperidol: a case series. AB - Six case reports are presented that describe the use of intravenous haloperidol for patients with migraine headache. Haloperidol was used in a dose of 5 mg following a 500- to 1000-cc bolus of normal saline. Headache was completely or substantially relieved in all six patients 25 to 65 min after administration of haloperidol; the median time until discharge was 51 min. Side effects were minimal or nonexistent. None of the patients returned to the Emergency Department (ED) for any reason over the next 48 h. It is concluded that haloperidol may play a role in treatment of migraine headache in the ED, and that further study is warranted. PMID- 7782619 TI - The incidence and effects of motion sickness among medical attendants during transport. AB - Motion sickness is a common and often debilitating problem. The purpose of this study was to determine the incidence and effects of the motion sickness syndromes, the Nausea and Sopite Syndromes, among medical transport personnel. Members of the Transport Teams of the University of North Carolina Hospitals completed a questionnaire to identify a history of susceptibility to motion sickness. An additional questionnaire evaluated each individual for symptoms of motion sickness during transport. The Digit Span Test portion of the Mini-Mental Status Examination (DST-MMSE) was used to evaluate cognitive function after transport. Control data on each subject were obtained by testing during nontransport shifts. The Nausea Syndrome was observed during transport in 46% of subjects; 65% experienced symptoms consistent with the Sopite Syndrome. Pretransport surveys were predictive of the Nausea Syndrome, but not of the Sopite Syndrome. The Nausea Syndrome was related to subjective assessments of the severity of motion experienced; the Sopite Syndrome did not correlate with the severity of motion. The DST-MMSE scores after transport were significantly lower than scores during nontransport periods in 85% of personnel. We conclude that transport personnel are susceptible to motion sickness manifested by both the Nausea Syndrome and the Sopite Syndrome. The presence of motion sickness is associated with a significant decline in performance on tests of attention and concentration. PMID- 7782620 TI - Police perception of intoxication among injured pedestrians. AB - To assess police officers' accuracy in perceiving alcohol or drug intoxication of injured pedestrians, blood test results from pedestrians struck by vehicles and admitted to a Level I trauma center for a 3-year period were linked to police reports of the crashes. Police officers were 64.5% sensitive and 99.3% specific in identifying alcohol use in injured pedestrians when blood tests were positive for alcohol, and 2.2% sensitive and 100% specific in identifying other drug use when blood tests were positive for drugs other than alcohol. Those with higher blood ethanol levels were more often correctly assessed to be under the influence. Injury Severity Score and the presence of head injuries had no apparent effect on police assessments. In conclusion, police assessment of substance abuse is extremely specific, but not particularly sensitive. Efforts are needed to improve police evaluations. The effect of increased legal actions on recurrent alcohol and drug-related injuries remains to be seen. PMID- 7782621 TI - Hydropneumothorax due to tuberculosis. AB - Pulmonary tuberculosis, a disease largely limited to third-world populations only 15 years ago, is increasingly becoming a public health problem again in the U.S. We review an emergent presenting feature of tuberculosis--spontaneous pneumothorax--that may now be seen more commonly in emergency departments (EDs). Pneumothorax must be quickly and effectively managed in the ED. In addition, the emergency physician should readily consider tuberculosis as an etiology in any patient with a spontaneous pneumothorax and a significant prodromal illness or a history of exposure to tuberculosis so that contagion precautions may be instituted promptly. PMID- 7782622 TI - Psychogenic status epilepticus. AB - A patient was brought to the Emergency Department in presumed status epilepticus. However, the seizure had many of the clinical characteristics that, in combination, were suggestive of a psychogenic event including asynchronous extremity movements, forward pelvic thrusting, and geotrophic eye movements. An arterial blood gas and serum electrolytes were normal despite one-half hour of tonic-clonic activity, and supported the diagnosis of a nonneurogenic event. The patient became conversant toward the end of the event, which confirmed that the seizure was nonepileptogenic. PMID- 7782623 TI - Bilateral inferior glenohumeral dislocation: luxatio erecta, an unusual presentation of a rare disorder. AB - Luxatio erecta, or inferior shoulder dislocation, is a rare form of shoulder dislocation. The case of a patient presenting with bilateral luxatio erecta, which was initially felt by EMS personnel to be an hysterical reaction, is discussed. An awareness of this rare entity, the potential-associated musculoskeletal and neurovascular injuries, and the proper treatment are essential for emergency physicians. PMID- 7782624 TI - Reversible acquired tracheobronchomalacia of a combined crescent type and saber sheath type. AB - A case of tracheobronchomalacia (TBM) in a 71-year-old woman, who had suffered a cough syncope, is reported. It was a combination of both the crescent type (the posterior membranous portion of trachea or bronchus protrudes into the lumen) and the saber-sheath type (the lateral cartilaginous wall of trachea or bronchus protrudes into the lumen). In this patient, acute bronchitis had developed superimposed upon a chronic bronchitis in addition to age-related regressive changes of the trachea and bronchus. A TBM due to acute inflammation can be reversible, but aggressive airway management as well as medical treatment of the underlying inflammation are critical to a successful outcome. PMID- 7782625 TI - Neonatal Trichomonas vaginalis infection. AB - Clinical infection with Trichomonas vaginalis (T. vaginalis) in the neonate is an unusual occurrence. We present a case of T. vaginalis in a 2-week-old girl with vaginal discharge. Our patient had complete resolution of symptoms after treatment with metronidazole. We found few references in the medical literature on the treatment of this condition. This report discusses the pathogenesis and treatment of T. vaginalis in the neonate. PMID- 7782626 TI - Steam vaporizer burn injuries. AB - Steam vaporizers increase indoor relative humidity by releasing steam into the air. The temperature of the steam is sufficiently high to cause severe burns. We report two cases of children who received partial thickness burns from steam vaporizers. Because of the high risk of burn injury, the manufacturers should be required to label the surface of the boiling chamber of the vaporizer with a warning statement. PMID- 7782627 TI - The effect of cocaine and amphetamines on vital signs in trauma patients. AB - The object of this study was to determine if the presence of sympathomimetics (cocaine, benzoylecgonine, or amphetamine), detected by routine urine toxicology screen, affect the initial presenting pulse, blood pressure, respiratory rate, or level of consciousness in trauma patients. A retrospective chart review was performed on 1,679 patients enrolled in an urban level 1 trauma registry between October 1987, and July 1992, for whom complete toxicology data were available. There were no clinically significant differences in the vital signs of patients with positive toxicology screens and those with negative screens. There was a statistically significant increase in prehospital respiratory rate among patients with benzoylecgonine or amphetamines on admission toxicology screens when potential confounding factors were controlled. However, these effects disappeared upon arrival at the hospital. The detection of sympathomimetics by toxicology screening had no effect on pulse and systolic blood pressure when age, sex, mechanism, type, and severity of injury, prehospital IV fluid volume, and alcohol intoxication were controlled. PMID- 7782628 TI - Acute ischemia of the hand following intra-arterial oxymetazoline injection. AB - Acute ischemia of the hand following intra-arterial injection of a drug is an infrequent problem, but it requires urgent medical attention. In this report, a patient injected a nasal decongestant, oxymetazoline hydrochloride (Afrin), into his radial artery. This resulted in severe burning pain, and cyanotic, cold, and pulseless hand, suggestive of acute ischemia. Intra-arterial papaverine, nifedipine, anticoagulation with heparin, prednisone, and stellate ganglion block did not improve the hand circulation. Development of gangrene necessitated a disarticulation at the wrist joint. Diagnosis, complications, and therapeutic measures of acute hand ischemia secondary to intra-arterial drug injection are discussed. PMID- 7782629 TI - Congestive heart failure and pulmonary edema for the emergency physician. AB - Congestive heart failure (CHF) and pulmonary edema are major health problems in the United States as well as across the rest of the developing world. The prevalence of CHF and pulmonary edema in the general population results in a significant number of these patients presenting to Emergency Departments (EDs). Mortality from these disorders is substantial, with a 5-year mortality rate for patients requiring hospitalization of approximately 50%. Understanding of the clinical syndromes of CHF and pulmonary edema requires review of the basic determinants of cardiovascular performance. Preload, afterload, contractility, and heart rate may all be modified by pharmacological or mechanical techniques. Diuretics, vasodilators, cardiac glycosides, and other inotropes all may play a role in the ED management of CHF. In rare instances, mechanical devices for support of the heart and circulation may be indicated. PMID- 7782630 TI - Bidirectional tachycardia associated with digoxin toxicity. PMID- 7782631 TI - Management of hymenoptera sting anaphylaxis: a preventive medicine survey. AB - The evaluation of aftercare instructions given to patients suffering from hymenoptera sting anaphylaxis was the objective of the study. Part of this evaluation included asking the physicians questions to examine the knowledge on which they based their aftercare instructions. Survey questionnaires were completed by 124 of 174 (71%) physicians who worked in an emergency department or urgent care center. Fifty-eight percent of the physicians never provided written avoidance instructions, 24% provided or prescribed anaphylaxis ID bracelets, 44% referred all of their patients to an allergist for further evaluation, and 73% reported prescribing an Epi-pen or Ana-kit to all hymenoptera sting anaphylaxis victims. Twenty-four percent of physicians did not know where to obtain anaphylaxis identification bracelets. This survey demonstrates that a substantial number of physicians practicing emergency medicine are not providing appropriate aftercare instructions to patients, and substantiates the need for educational efforts to increase the awareness of physicians concerning the implications of hymenoptera allergy and the value of proper preventive measures. PMID- 7782632 TI - Appendicitis: a continuing diagnostic challenge. PMID- 7782633 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: traumatology, Part 1. AB - This is the 30th article in a continuing series of objectives to direct emergency medicine resident experiences on off-service rotations. Because injuries account for tremendous morbidity and mortality, management of trauma is an essential part of training in emergency medicine. Instruction in traumatology during off-service rotations may be conducted at the bedside in difficult and demanding clinical settings. Therefore, it is essential for residents to have specific goals and objectives to guide their acquisition of knowledge required to make rapid, accurate decisions for patients with major trauma. PMID- 7782634 TI - Comparison of magnetic resonance tomography with computerized axiography in diagnosis of temporomandibular joint disorders. AB - This study compared the accuracy of two noninvasive methods, computerized axiography and magnetic resonance tomography (MRT), in diagnosing temporomandibular joint (TMJ) disorders. Forty-seven subjects underwent axiography and subsequent assessment of the TMJ by MRT. The statistical analysis referred to the correlations of the most relevant clinical diagnoses, i.e., no appreciable disease, disk displacement with reposition, disk displacement without reposition, morphologic alterations, and hypermobility of the condyle. In 70% of the disk-displacement-with-reposition and disk-displacement-without-reposition patient groups, axiography and MRT gave the same information. In other patient groups, the axiography findings agreed with the MRT findings in 45% of the cases. It was concluded that although a large percentage of morphologic alterations could be detected by MRT, axiography determined the dysfunctional dynamics more clearly. PMID- 7782635 TI - Perspectives on craniofacial asymmetry. I. The biology of asymmetry. AB - Part I introduces the survey and presents a topic outline of the six parts that make up this series of articles on craniofacial asymmetry. The discussion in Part I considers normal variation, normal and abnormal laterality, types of anomalies that may be asymmetric, and finally, some well-known causes of craniofacial asymmetry. PMID- 7782636 TI - Combined use of bone grafts and implants in the severely resorbed maxilla. Postoperative evaluation by computed tomography. AB - Combined horseshoe-shaped iliac bone grafts and Branemark fixtures were used to rehabilitate patients with severely resorbed maxillae. Twenty patients were followed-up by computed tomography (CT) examination with axial slices to assess the fixture sites and to study the changes in height and width of the bone graft 3 weeks and 3, 6, 12, and 24 months postoperatively. The mean height of the bone graft at the 3-week postoperative examination was 8.2 mm; after 2 years the mean value had decreased to 6.2 mm. The height reduction occurred mainly between the 3 month and 1-year examinations. The mean width of the bone graft at the 3-week postoperative examination was 12.2 mm, and it decreased to 8.6 mm after 2 years. Most of the width reduction took place during postoperative months 1-3. From 1 year after the grafting procedure, the rate of reduction of both height and width was very low. PMID- 7782637 TI - Cervical spine injuries in patients with facial fractures: a 1-year prospective study. AB - A total of 582 consecutive patients with facial fractures were investigated prospectively for evidence of a concomitant cervical spine injury. Of them, 1.04% (6) were found to have a cervical spine injury, all having occurred in road traffic accidents. Only two of the injuries were diagnosable on standard, three view, plain cervical spine radiographs. Four were diagnosable from computerized tomography scan, while the remaining two required stress views under radiographic screening for definitive diagnosis. PMID- 7782638 TI - Correlation of histopathologic findings with clinical and radiologic assessments of cervical lymph-node metastases in oral cancer. AB - The accuracy of preoperative diagnosis of cervical lymph-node metastasis in oral cancer was assessed by comparing the histopathologic findings in 136 sides of neck dissection with physical examination under anaesthesia (EUA) and computerized tomography (CT) assessments of the metastatic status. The overall accuracy of EUA and CT assessments was 72% and 73%, respectively, and a combination of both methods resulted in sensitivity and specificity rates of 55% and 78%, respectively. Twenty-three of the 51 histologically positive necks had been assessed as negative on both EUA and CT. Six of these contained only micro metastases, and in another 10, the largest positive node was 1.5 cm or less. Extracapsular spread of metastatic carcinoma was found in 12 of the 23 EUA and CT false-negative dissections. Most of the 21 histologically positive necks which had been correctly assessed as positive on both EUA and CT contained enlarged metastatic nodes, fused nodal masses, extensive extracapsular spread, or more than one of these features. Three of the 85 histologically negative necks had been assessed as positive on both EUA and CT; eight had been positive on EUA alone, and another eight on CT alone. Reactive nodal hyperplasia or sialadenitis was seen in most false-positive dissections. We conclude that the accuracy of preoperative diagnosis of metastasis by routine methods remains poor, and that EUA and CT are reliable only in patients with bulky metastatic deposits. PMID- 7782639 TI - The osteoseptocutaneous or purely septocutaneous peroneal flap with a supramalleolar skin paddle. AB - There are many indications for using the peroneal flap in maxillofacial reconstructive surgery, either as a cutaneous flap or combined with a fibula segment. According to the results of our anatomic study and clinical experience with 14 patients, the supramalleolar segment is especially suitable as donor region because the highest density of septocutaneous perforating vessels exists here; hence, the preparation of a long vascular pedicle is possible. The donor site leaves an acceptable defect with appropriate patient selection. PMID- 7782640 TI - Flow cytometric analysis of nuclear DNA content in oral leukoplakia: relation to clinicopathologic findings. AB - DNA ploidy of 50 biopsy specimens of oral leukoplakia was investigated by flow cytometry, and the results were compared with the clinicopathologic appearances. The aneuploidy rate of the leukoplakias was 17/50 (34%), and the mean DNA index (DI) of the aneuploid lesions was 1.22, with a range from 0.70 to 1.84. The incidence of the aneuploidy was significantly (P < 0.01) higher in nonhomogeneous leukoplakias (11/18) than in homogeneous lesions (6/32). The aneuploidy rate of the severely dysplastic leukoplakias (11/17) was significantly higher than those of the mildly dysplastic (4/22; P < 0.01) and the nondysplastic (2/11; P < 0.02) lesions. A significant (P < 0.01) difference in the aneuploidy rate was also observed between tongue (12/23) and gingival (2/18) leukoplakias. PMID- 7782641 TI - Imaging of mandibular cysts with a dental computed tomography software program. AB - Twelve mandibular cysts were examined radiographically by conventional panoramic radiography (orthopantomography (OPG)), mandibular tomography (MT), and axial computed tomography (CT). The axial CT scans were reformatted with both a conventional program and a dental CT software program that displays exactly proportional cross-sectional views. The radiographic images obtained with these four examination modalities were compared for visualization of mandibular anatomy, delineation of the mandibular canal, detection of cortical bone involvement, and cystic volume. CT and especially the dental CT program rated significantly (P < 0.001) higher in all points examined than two-dimensional methods (OPG, MT). The dental CT program was found to be superior for detecting cortical bone involvement (P < 0.02) and delineation of the mandibular canal (P < 0.02) to the conventional CT program. PMID- 7782642 TI - Comparison of epithelial dysplasia--the 4NQO rat palate model and human oral mucosa. AB - Epithelial dysplasia in the rat palatal mucosa was induced by application three times a week of the carcinogen 4-nitroquinoline 1-oxide (4NQO). With the Epithelial Atypia Index (EAI), the successive stages of 4NQO-induced epithelial dysplasia were compared with specimens of human oral epithelial dysplasia. It appeared that there was a close similarity between the histologic features of 4NQO-induced dysplasia in the rat palatal mucosa and human oral epithelial dysplasia. Thus, the 4NQO rat palate model seems to be appropriate to study and assess new treatment modalities of premalignant epithelial lesions of the oral mucosa in man. PMID- 7782643 TI - Perspectives on craniofacial asymmetry. II. Asymmetric embryopathies. AB - Asymmetric embryopathies--severe malformations and disruptions--that affect the craniofacial region are discussed, including anomalies of the eye, nose, mouth, and ear. Asymmetric Tessier clefts are also discussed. PMID- 7782644 TI - Prefabricated prostheses for the reconstruction of skull defects. AB - Cranioplasties using intraoperatively modeled prostheses may fail to create harmonic contours with long-term stability. In contrast, preoperative modeling would allow more sophisticated planning of the contour and better preparation of the implant material, if a sufficiently precise model of the defect-site was available. In this respect, computer aided design and manufacturing (CAD/CAM) techniques based on helical computed tomography (CT) data are successfully used for the prefabrication of prostheses: An individual computer-based 3-dimensional model of the bony defect is generated after acquisition, transfer and evaluation of the CT data; from this freeform surfaces geometry an individual and "idealized" prosthesis-geometry is derived and fabricated by a numerically controlled milling machine using modern industrial CAD/CAM-systems and design software. The margins of this prosthesis-geometry are generated by the borders of the defect and the surface by considering the non-affected neighbouring contours. Cranioplasties in cases of large postsurgical skull defects are presented as the first clinical applications of this new method, which also allows the use of titanium and fabrication of integrated fixation-devices. PMID- 7782645 TI - Intraoperative navigation in oral and maxillofacial surgery. AB - Surgical procedures in the oral and maxillofacial region may be difficult in areas of complex anatomy. Up to now, surgical planning has been based almost exclusively on the surgeon's experience and on the interpretation of 2 dimensional (2D) radiologic information. Our experiences with a commercially available 3D navigation system (Viewing Wand, ISG, Mississauga, Ontario, Canada) is reported upon. The system consists of a mechanical operating arm with 6 joints and 6 degrees of freedom working as a 3D digitizer and is interfaced to a computer graphics workstation. After registration of the position of the patient's head in relation to the tip of the instrument on the navigation arm, the surgeon can observe the 3D position and direction of the instrument in use on the monitor, i.e. on the computed tomography and/or magnetic resonance tomography images of the patient taken before. In 40 interventions performed so far, the accuracy was 2 mm and better. 3 cases are presented in this paper. The system facilitates surgery especially in anatomically complicated situations without the risk of damaging neighbouring structures. Planning of surgical interventions is much easier. By using computer assisted simulation and navigation systems, we expect an improvement in quality and a reduction in surgical risks. Thus, "looking ahead" surgery has become possible. More extensive and more radical interventions are likely to be performed in the near future. Responsibility for the surgical intervention, however, remains exclusively with the surgeon. PMID- 7782646 TI - Advances in interactive craniofacial surgery planning by 3D simulation and visualization. AB - In craniofacial surgery careful preoperative planning is essential. Traditional preoperative work-up consists of cast model surgery, cephalometric prediction tracing and analysis of photographs. Recently, we introduced 3-dimensional (3D) computed tomography (CT) model surgery in our preoperative work-up and presurgical prediction of the postoperative result. However, only limited information can be extracted concerning soft tissue changes which are most important for the patients' postoperative appearance. We propose a new system which will allow a precise preoperative visualization of not only bony structures but also the soft tissue surfaces. 3D CT data of the skull are integrated with 3D surface data acquired by laser scanning. Based on the 3D CT data the bony structures are segmented automatically and processed interactively to simulate the planned surgical procedure. Afterwards, the 3D soft tissue changes resulting from the shifting of bony segments are computed. The postoperative appearance of the patient is visualized using computer animation techniques. PMID- 7782647 TI - CT data acquisition as a basis for modern diagnosis and therapy in maxillofacial surgery. AB - More than 20 years after its introduction computed tomography has become a routine method in the diagnostic work-up of traumatic and neoplastic disorders in maxillofacial surgery. Short acquisition times of 1 sec per image reduce motion artifacts and permit increased numbers of patient examinations. Different reconstruction algorithms allow specific evaluation of either osseous or soft tissue structures. By adjusting window center and window width the 2048 attenuation values can be transformed into the visible gray scale. Single sequential slices--as employed in routine diagnosis of tumor patients--still yield the highest image quality. Fast volume data acquisition associated with spiral scanning proves to be of special benefit in trauma patients. The resulting data set can be used for reconstruction of single slices, 2-dimensional (2D) reformated images in all planes and 3D surface rendering. PMID- 7782648 TI - 2D and 3D CT reconstructions of the facial skeleton: an unnecessary option or a diagnostic pearl? AB - The introduction of spiral computed tomography (CT) has been a major advance in CT scanning, particularly considering the reduction in acquisition time and improvements in 2-dimensional (2D) and 3D reconstructions. 314 out of 1262 CT examinations of the midface and jaws executed from September 1993 to September 1994 were performed in the spiral mode. Our experience is critically reviewed and a guideline for the use of spiral CT scanning of the midface and jaws for various diagnostic purposes is established: Complex midface fractures require axial spiral CT scanning with secondary coronal reconstructions Because of the long processing time 3D reconstructions are reserved for planning surgical repair of craniofacial malformations. Dental CT scans with calculation of panoramic images provide important information prior to dental implant surgery and repair of alveolar clefts. PMID- 7782649 TI - 3D sonography. AB - A method of 3-dimensional (3D) sonography (US) is described in this paper. Special emphasis is laid upon the basic problem of generating well-orientated 3D visualizations on the basis of different evaluation techniques. Furthermore, some problems of data acquisition and data processing using US are presented. Alternative solutions thereto are briefly discussed. PMID- 7782650 TI - CAD by processing of computed tomography data and CAM of individually designed prostheses. AB - In the past an economic fabrication of individual prostheses used in reconstructive cranio-maxillo-facial surgery was not possible due to technical deficiencies. Now, through the consistent use of the most modern computer-based techniques developed in the field of industrial engineering, these costs can be reduced to an economic level. Mathematical freeform surfaces models are first created from helical computed tomography data. These serve as the basis for an efficient and idealized construction of prostheses geometries, and provide control-data for a computerized numerical control-fabrication. In 4 clinical cases this new processing technique has successfully been utilized in the fabrication of individually designed prostheses for the reconstruction of skull defects. The range of opportunities offered is reflected not only in the great variety of possible geometric details, but also in the fact that the prostheses may be manufactured--partly using indirect impression-taking techniques--from 3 different biocompatible materials so far and other applications are likely to turn up. PMID- 7782651 TI - Stereolithography in oral and maxillofacial operation planning. AB - Stereolithography (STL) is a method of organ-model-production based on computed tomography scans which enables the representation of complex 3-dimensional anatomical structures. Surfaces and internal structures of organs can be produced by polymerization of UV-sensitive liquid resin using a laserbeam. In oral and maxillofacial surgery this technique is advantageous for reconstruction of severe skull defects because a more accurate preoperative planning is possible. Using recently developed software we are able to reconstruct unilateral bony defects by virtual mirror imaging of the contralateral side and production of a STL mirror model as well as the reconstruction of non-mirrorable defects by superposition. Advantages of STL are the representation of complex anatomical structures, high precision and accuracy, and the option to sterilize the models for intraoperative use. More accurate planning using this method improves postoperative results, decreases risks and shortens treatment time. PMID- 7782652 TI - [F-waves in brachial plexus palsy correlated to the prognosis of intrinsic paralysis]. AB - F-waves were examined in 80 nerves of 40 brachial plexus palsies in 37 cases. The electrical responses were evoked by 30 consecutive supramaximal electric stimuli to the median and ulnar nerves at the wrist and elbow, and recorded from the abductor pollicis brevis and abductor digiti minimi muscles. Three parameters in the F-waves were analyzed--conduction velocity, the difference between the maximal and minimal latencies, and the amplitude. In all cases, examinations were done repeatedly to detect changes in these parameters, and the results were compared with the clinical course of the intrinsic muscle function. Twenty-seven cases were investigated before and after explorative surgery. The findings were divided into four groups. The 1st group consisted of 12 nerves in which F-waves were not recorded. The intrinsic muscle power in this group was zero, and did not show any restoration. The 2nd group consisted of 10 nerves in which the conduction velocity was delayed. The muscle power in this group was fair, poor or trace, and there was no change in conduction velocity and muscle function. The 3rd group consisted of 18 nerves in which parameters other than the conduction velocity were abnormal, and the intrinsic muscle power in this group was fair, good or normal. In 7 of these nerves, the large latency difference decreased to normal at the 2nd, 3rd or 4th test with functional recovery in the intrinsic muscle. The high amplitude also changed to normal at the 2nd test with functional recovery. The 4th group consisted of 40 nerves in which all the parameters were normal and had full intrinsic muscle power. In conclusion, an examination of the F-waves was valuable to indicate the prognosis of the intrinsic muscle in the hand in brachial plexus palsy. PMID- 7782653 TI - [Results after cemented total knee arthroplasty: a follow-up study over 5-to-14 years]. AB - Eighty-five cemented total knee arthroplasties were followed for five to fourteen years (mean 7.8 years). The clinical evaluation was excellent or good in 85% of this series. However, a complication developed in 15 knees (17.6%), and two thirds of these complications were found in the patello-femoral joint. One further case developed an infection (1.2%), and four others (4.7%) developed an aseptic loosening. Over all, 8 cases (9.4%) required revision surgery. Asymptomatic wear was seen to progress in some implants involving thin polyethylene, although their clinical results were rated as excellent. The outcome of the cemented knee arthroplasties was considered as acceptable at present, but improved surgical techniques and measures against polyethylene wear are required for future improvement in this surgery. PMID- 7782654 TI - [Femoral neck and iliac bone histomorphometry in femoral neck fracture]. AB - Involutional osteoporosis is a risk factor for femoral neck fracture in elderly people. This study was designed to evaluate the bone mass and quality of the femoral neck specimen obtained directly from the femoral neck at the time of hip surgery. An iliac bone biopsy was also performed in some cases. A histomorphometric analysis of the femoral neck was performed in 31 women with a femoral neck fracture, aged 64-104 (mean age 76.2), and in 19 women with osteoarthritis of the hip, aged 50-77 (mean age 64.3) as a control. The cortical thickness of the lateral, anterior and posterior aspects of the femoral neck was significantly less in the fracture group than in the osteoarthritis group. However, there was no significant difference in the medial cortical thickness between the two groups. The fracture group exhibited an increased resorption cavity area and intracortical porosity in the cortical area as well as increases in the eroded surface and osteoclast number in the endocortical envelope. The bone volume in the cancellous envelope of the medial femoral neck was significantly lower in the fracture group. Most parameters of the iliac bone were not correlated with those of the femoral neck in either group. Our findings suggested that a femoral neck fracture was associated with a decreased cortical thickness in the femoral neck. Increased intracortical porosity and a low cancellous bone volume were also critical factors in femoral neck fragility, and an iliac bone biopsy did not necessarily reflect the femoral neck bone status. PMID- 7782655 TI - [Triangular fibrocartilage complex: functional anatomy and histology]. AB - The functional anatomy and histology of triangular fibrocartilage complex (TFCC) were investigated using 20 wrists from fresh cadavers, and a functional model of TFCC was proposed. The dynamic changes in the TFCC during pronation and supination were examined from both the proximal and distal sides. The distal side of the TFCC consisted of the disc proper (DP), the meniscus homologue (MH), the ulnolunate ligament (UL), and the ulnotriquetral ligament (UT). The prestyloid recess was observed between the DP and MH. The ulnar collateral ligament (UCL) existed at the ulnar side of the TFCC and consisted of the sheath floor of the extensor carpi ulnaris (ECU) with relatively loose ligamentous tissue recognized as 6U-portal in arthroscopy. The fan-shaped triangular ligament spreading from the fovea of the ulna was observed on the proximal side of the TFCC. It was considered to be the real radioulnar ligament connecting the radius and ulna. During pronation and supination, little deformity in the DP was observed, while the ulnar insertion of the triangular ligament was twisted. The UCL was distorted dorsally in pronation and volary in supination. In the coronal section of the TFCC, the area surrounded by the DP, MH and UCL was relatively soft and loose, and was considered to have served as a cushion during pronation and supination. From these findings, the TFCC was separated into three components; the distal component which acted like a hammock to suspend the carpus, the triangular ligament as the proximal component which stabilized the radius to the ulna, and the UCL as the ulnar component which stabilized the carpus to the ulna. We have proposed a suspension theory to account for the stability and mobility of the TFCC during pronation and supination when these three components suspend each other. The function of the TFCC can be fully accounted for by our theory. PMID- 7782656 TI - [Correlation between the concentration of 1,25 alpha dihydroxyvitamin D3 receptors and growth inhibition, and differentiation of human osteosarcoma cells induced by vitamin D3]. AB - It has been previously reported that several human cancer cell lines possess specific receptors for 1,25-dihydroxyvitamin D3. In the present study, the concentration of the 1 alpha,25 dihydroxyvitamin D3 receptors has been determined in four human osteosarcoma cell lines--MG63, OST, MNNG-HOS, and KHOS-NP, and we report the effect of 1 alpha, 25 dihydroxyvitamin D3 on these cells. The concentration of 1 alpha, 25 dihydroxyvitamin D3 receptors in MG63, OST, MNNG-HOS and KHOS-NP was 31.1, 12.1, 5.9 and 3.0 fmol/mg of cytosol protein, respectively. These cell lines were classified into two groups according to the concentration of the receptors. The two receptor-rich cell lines were MG63 and OST, and the receptor-poor cell lines were MNNG-HOS and KHOS-NP. In a colony-forming assay, 1 alpha, 25 dihydroxyvitamin D3 (10(-8)M, 10(-9)M) was found to significantly suppress the growth of the receptor-rich cell lines (p < 0.01), but did not suppress that of the receptor-poor cell lines. In an antitumor assay, athymic mice received a transplantation of tumor cells and were treated with 2.5 nmol/kg of 1 alpha hydroxyvitamin D3. Then the relative mean weight of the tumor was measured (MG63 was, however, not transplantable into athymic mice.) As a result, 1 alpha hydroxyvitamin D3 was found to have significantly suppressed the relative mean tumor weight of OST and MNNG-HOS compared with a control group (p < 0.05), but did not suppress that of KHOS-NP. Histologically, 1 alpha hydroxyvitamin D3 induced marked chondrogenetic differentiation in OST alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782657 TI - [An experimental study on the prevention of postlaminectomy scar formation: efficacy of interpositional collagen-sponge]. AB - The efficacy of collagen-sponge to reduce postoperative scar formation was investigated in 65 Japanese white rabbits that received laminectomy in the 7th and 8th thoracic vertebra. The defect after laminectomy was filled by collagen sponge in 25 rabbits, by free fat in 20 rabbits, and by nothing in 20 rabbits as controls. The animals were sacrificed 2, 4, 8 and 12 weeks and additional 5 rabbits of which defects were filled with collagen-sponge were sacrificed after 24 weeks. All the defects were examined histologically. At 4 weeks after laminectomy, the defects filled by collagen-sponge showed that fibrous tissue had invaded into the sponge, but there was no remarkable adhesion to the dura mater. At 8 weeks, the defect with collagen sponge showed foaming cells, and no thickening of the dura mater was observed. At 12 weeks, the grouping of foaming cells was partially replaced by fat cells. At 24 weeks, most of the foaming cells were replaced by fat cells, and the defect was then similar to that filled by free fat at 12 weeks. In contrast, the defect with no interposed membrane was already filled with fibrous tissue at 4 weeks, and adhesion to the dura mater was observed. Although the free-fat graft at 12 weeks postoperatively showed no remarkable adhesion around the dura mater, infiltration of fat tissue into the spinal canal was observed in 2 of 5 rabbits. These results indicated that collagen-sponge can be utilized as a new biomaterial to effectively prevent scar formation after laminectomy. PMID- 7782658 TI - [The effect of 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71) on callotasis in rabbit]. AB - To evaluate the effects of 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71) on callotasis, we measured the bone mineral content (BMC) using dual energy X-ray absorptiometry (DXA) and compared the results with radiographical and histological findings, in an experimental model. Leg lengthening by callotasis was performed on 37 10-week-old Japanese white rabbits. The rabbits were divided into two groups; those in Group A (n = 19) received no medication and those in Group B (n = 18) received ED-71 (0.05 micrograms/kg body weight) twice a week following osteotomy. In both groups, from 10 days after the osteotomy, the bone was lengthened a total of 10 mm at a rate of 0.5 mm every 12 hours (1.0 mm/day) for a further 10 days. After completion of distraction, the bone mineral content (BMC) of the newly formed bone at the site of lengthening was then measured by DXA each week for 15 weeks, and the DXA findings were compared with those from radiographical and histological studies. The BMC of the newly formed bone at the site of the lengthening in both groups increased and reached a peak at two weeks after completion of the distraction. Then, the BMC gradually decreased and reached a plateau after a further 8 weeks. The BMC in Group B was significantly higher than that in Group A, and this correlated with the radiographical and histological findings. We concluded that the change in BMC at the site of the lengthening corresponded with the radiographical and histological findings, and that ED-71 administration may increase the callus formation at the site of leg lengthening. PMID- 7782660 TI - Noninvasive continuous blood pressure measurement during anaesthesia: a clinical evaluation of a method commonly used in measuring devices. AB - The objective of the study was assess the utility during anaesthesia of noninvasive continuous blood pressure measurement techniques which use intermittent oscillometric blood pressure measurement for their calibration. The assessment was performed by comparing noninvasive blood pressure with intra arterial blood pressure. The noninvasive blood pressure measurement device used for evaluation was the NCAT N-500 which uses tonometry for its continuous measurements. Fifteen patients were studied. In 10 patients the intra-arterial blood pressure curve (IBP) was recorded from the radial artery (radial artery group), and in 5 patients it was recorded from the brachial artery (brachial artery group). In all patients the oscillometrically calibrated tonometric blood pressure (OTBP) was recorded from the other arm. To discriminate between calibration dependent measurement error and tonometric measurement error, the OTBP signal was recalibrated against the IBP signal to get the intra-arterial calibrated tonometric pressure curve (ITBP). OTBP-IBP reflected the overall measurement error, ITBP-IBP the error of the tonometric measurement, and OTBP ITBP the calibration dependent measurement error. According to criteria formulated in the discussion the accuracy and agreement of the ITBP-IBP measurements were clinical acceptable. Accuracy and agreement of OTBP-IBP and of OTBP-ITBP were not clinical acceptable. Correlation of dynamic behavior was lower for OTBP than for ITBP. A significant effect of site difference between calibration measurements and continuous measurements was not found. It is concluded that the approach of continuous noninvasive blood pressure measurement based on the combination of two different measurement methods, in which the continuous method is calibrated by the oscillometric method, lead to clinical unacceptable accuracy and agreement in the patient group studied. PMID- 7782659 TI - [Osteoconduction in porous hydroxyapatite ceramics grafted into the defect of the lamina in experimental expansive open-door laminoplasty in the spinal canal]. AB - We have investigated the osteoconduction in porous hydroxyapatite ceramics grafted into the defect of the lamina of dogs in expansive open-door laminoplasty. Porous Hydroxyapatite block (HAB) was sintered at 900 degrees C with size of 4 x 7 x 19 mm, a mean pore diameter of 90 microns and a void volume of 70%. The operation was performed in 29 dogs. The animals were sacrificed at three or at six months after the operation (the three-month group and the six month group). After the grafted HABs with adjacent vertebrae were removed, the stability of the grafted HABs was manually evaluated. The HAB was firmly fixed to the laminae in 14 of 20 cases. It seemed that the stability of the HAB was poor in those cases in which the HAB had not been tightly sutured. To investigate osteoconduction, serial sections of the laminar bones including the HAB were prepared without decalcification and were examined histologically. New bone formation in the pores of the HAB was found in all cases. However, the osteoconduction rate was higher in the six-month group than in the three-month group (p < 0.01). And the osteoconduction rate was higher in those cases in which the HAB was firmly fixed to the laminae than in those with a loosely fixed HAB. Bone ingrowth in the HAB was frequently observed in the zone adjacent to the bone, more so than in other zones. Osteoconduction appeared to occur at the contact surface and to extend towards the center of the HAB. PMID- 7782661 TI - Introduction of knowledge bases in patient's data management system: role of the user interface. AB - As the number of signals and data to be handled grows in intensive care unit, it is necessary to design more powerful computing systems that integrate and summarize all this information. The manual input of data as e.g. clinical signs and drug prescription and the synthetic representation of these data requires an ever more sophisticated user interface. The introduction of knowledge bases in the data management allows to conceive contextual interfaces. The objective of this paper is to show the importance of the design of the user interface, in the daily use of clinical information system. Then we describe a methodology that uses the man-machine interaction to capture the clinician knowledge during the clinical practice. The different steps are the audit of the user's actions, the elaboration of statistic models allowing the definition of new knowledge, and the validation that is performed before complete integration. A part of this knowledge can be used to improve the user interface. Finally, we describe the implementation of these concepts on a UNIX platform using OSF/MOTIF graphical interface. PMID- 7782662 TI - Automated anaesthesia record systems, observations on future trends of development. AB - The introduction of electronic anaesthesia documentation systems was attempted as early as in 1979, although their efficient application has become reality only in the past few years. Today, documentation technology is offered by most of the monitor manufacturers and new systems are being developed by various working groups. The advantages of the electronic protocol are apparent: Continuous high quality documentation, comparability of data due to the availability of a anaesthesia data bank, reduction of the workload of the anaesthesia staff and availability of new additional information. Disadvantages of the electronic protocol have also been discussed. Typically, by going through the process of entering data on the course of the anaesthetic procedure on the protocol sheet, the information is mentally absorbed and evaluated by the anaesthetist. This mental processing of information may, however, be missing when the data are recorded fully automatically--without active involvement on the part of the anaesthetist. It seems that electronic anaesthesia protocols will be required in the near future. The advantages of accurate documentation and quality control in the presence of careful planning will outweight cost considerations. However, at this time, almost none of the commercially available systems have matured to a point where their purchase can be recommended without reservation. There is still a lack of standards for the subsequent exchange of data and a solution to a number of ergonomic problems still remains to be found. PMID- 7782663 TI - Clinical evaluation of the 'head-up' display of anesthesia data. Preliminary communication. AB - To solve the problem of monitoring the patient during administration of anesthesia, a commercially available head-up display (HUD) was evaluated during one day of surgery at the Ohio State University Hospitals. This monitor is mounted on a headband worn by the anesthesiologist. It projects a monochrome image of monitor data directly into one eye. Eleven anesthesiologists tested the device. Most users were able to adjust to the monitor in about fifteen minutes. Nine of the testers expressed a desire to evaluate the monitor further. Their major complaints were that the connecting cable between the HUD and its computer was too short, the resolution of the monitor was inadequate, and the data on the screen were not organized in a familiar way. If these problems could be corrected, most users believed that this HUD could be a valuable tool to aid the anesthesiologist in the operating room. PMID- 7782664 TI - The calculation of linear dimension and image area using a digitising tablet and personal computer. AB - An inexpensive image-area and perimeter-length measurement system consisting of a personal computer and digital graphics tablet is described. A study to assess the efficacy of the system has shown that accuracy and reproducibility of area measurement increase with increasing size of cross-sectional area. The system generally underestimated all derived areas by less than 2%. Reproducibility of measurement, as defined by the coefficient of variation, was typically less than 2%; the greatest inaccuracies and variability occurring with shapes of smaller cross-sectional area. The system seems to be the least accurate when it measures shapes with rectangular symmetry. Neither direction of digitisation nor operator skill seemed to influence the measurement accuracy of the system. PMID- 7782665 TI - Implication of anaesthesiologists' varying location during surgery. AB - Anecdote indicates anaesthesiologists in the operating room are not invariably at the head of the operating table beside their equipment. The validity of this was investigated by a nationally distributed questionnaire. The results support the anecdotal evidence. The behaviour can be justified so supports a recommendation for appropriate visibility of information displays. Whether such action would improve patient safety is debatable. PMID- 7782667 TI - A short tutorial: The Internet as a global information source. PMID- 7782666 TI - Data processing in prehospital emergency medicine. AB - Information about the use of data processing systems in prehospital emergency medicine were collected, using a questionnaire sent to all German rescue helicopter bases. Twenty-seven of the 42 German rescue helicopter bases returned the questionnaire. At present, only 15 of them take advantage of electronic data processing. All of them enter their data manually by keyboard, automatic data transfer by means of a bar code reader is available at one base only. The stored data are used for statistical analysis (n = 15), quality assessment (n = 10), administration (n = 10), research (n = 9) and education (n = 7). Based on the data of this survey, one fifth of those who replied use their computer only for administrative purposes, the other also manage patient and mission data with their computer systems. Today, documentation of a rescue mission consists of patient data, vital data, mission data and information about the procedures carried out. The use of a computer system, however, requires more time and work than a handwritten record, when most of the data have to be entered manually using a keyboard. Future developments may include automated data transfer and digitization of handwritten documents to decrease the workload of the staff. For the automation of data transfer, configuration and synchronisation a standardized interface in all medical devices is required. There is a clear need for the use of data processing systems in emergency medicine. PMID- 7782668 TI - ECG of the month. The untamed heart. Atrial flutter. PMID- 7782669 TI - Deep neck space infections. AB - The incidence of deep neck space infections has dramatically decreased since the advent of antibiotics, but with delayed treatment they carry the potential for significant morbidity and mortality. Odontogenic infections with involvement of the submandibular space are the most common source of deep neck space infections in adults, whereas in the pediatric population the most common cause is acute tonsillitis with involvement of the peritonsillar space. The newest group of patients at risk for deep neck space infections are intravenous drug abusers who inject the major vessels of the neck. Knowledge of neck spaces and fascial relationships is important in understanding the presentation, treatment, and complications of deep neck space infections. The spaces, which are created by various fasciae of the head and neck, are only potential spaces in that under normal conditions they cannot be examined clinically or radiographically. As the spaces are invaded by bacteria, a cellulitis or abscess occurs, and this infection may travel through paths of least resistance from one space to another. PMID- 7782670 TI - The journal 100 years ago. May 1845 and 1895. PMID- 7782671 TI - Management of chronic ischemic heart disease. PMID- 7782672 TI - Positron emission tomography in the diagnosis and management of coronary artery disease. AB - Positron emission tomography has grown rapidly from a little-understood research tool into an exciting noninvasive method for the clinician to evaluate myocardial perfusion, metabolism, and cell-membrane function. There are three radionuclides that are currently being used widely in cardiac positron emission tomography. These are nitrogen-13 ammonia, rubidium-82, and fluorine-18 fluordeoxyglucose. Nitrogen-13 ammonia and rubidium-82 are used to assess the severity and location of coronary artery disease, while fluorine-18 fluordeoxyglucose can identify impaired but viable myocardium, thus aiding in the subsequent management of these patients. PMID- 7782673 TI - The exercise treadmill test for diagnosis and prognosis of coronary artery disease. AB - After more than 50 years of refinement, the exercise test remains a useful device for diagnosis and prognosis of coronary artery disease. In addition, it is within the range of skills of primary care physicians. Understanding that the exercise test is not a noninvasive angiogram, and that angiography primarily defines anatomy, emphasizes the complementary nature of the tests. The addition of thallium scintigraphy to the exercise test brings enhanced sensitivity and specificity in certain clinical settings. The use of exercise testing with or without thallium scintigraphy is not currently recommended for evaluation of dysrhythmias, pre-operative clearance, or screening of asymptomatic individuals. PMID- 7782674 TI - Ischemic heart failure. AB - Heart failure is a major and increasing public health problem. Coronary artery disease has become the major etiology of heart failure. The differentiation of viable from nonviable myocardium in patients with coronary disease and impaired left ventricular systolic function is an issue of extreme importance to the clinician. Several diagnostic modalities including thallium imaging, dobutamine stress echocardiography, and positron emission tomography have gained considerable acceptance as useful tools in detecting myocardial viability. The management of heart failure with preserved left ventricular systolic function includes the use of beta blockers, calcium channel blockers, and nitrates. In patients with heart failure and impaired left ventricular systolic function, angiotensin converting enzyme inhibitors have become an integral part of the medical management. In patients whose angina is unresponsive to the addition of nitrates, a trial of bet blockers should be attempted and first generation calcium blockers should be avoided. Revascularization should always be sought, particularly when myocardial viability has been established. PMID- 7782676 TI - Current trends and considerations in the surgical treatment of coronary artery disease. AB - Management of coronary artery disease has changed greatly in the past three decades. Surgical treatment has improved, especially with the introduction of bypass conduits, like the internal mammary artery, which possess a patency rate far superior to that of the saphenous vein. Use of this arterial graft has so encouraged surgeons that other autologous arterial grafts are being tried. Grafts from nonautologous sources are being investigated, but none have yet been found to approach the excellent performance of the internal mammary artery. While the surgical treatment for myocardial ischemia has greatly improved, characteristics of the patient population have not. Patients presently sent for surgery are older, in worse general health, and have poorer cardiac function and coronary disease than their counterparts of several decades ago. Nevertheless, expansion of surgical options, including cardiac transplantation has allowed even the highest risk patients to be considered for surgical intervention. PMID- 7782677 TI - Percutaneous interventions for ischemic heart disease. AB - In the United States, when necessary due to symptoms or prognosis, percutaneous coronary interventions are performed on patients with ischemic heart disease more frequently than is coronary artery bypass surgery. A wide array of options are available to the interventional cardiologist. Improvements over the 17 years that coronary balloon angioplasty has been performed have kept it the primary therapy. It is currently used safely and effectively in the majority of patients. The problems of abrupt closure, restenosis, and inadequate results in some complex lesions have spurred the development of intracoronary stents, coronary atherectomy and ablation devices, and coronary excimer lasers. Metallic stents perform well in large vessels to treat abrupt closures and to reduce restenosis, but confer a risk of hemorrhage. Specific complexities of lesion characteristics determine the effective use of atherectomy/ablation devices and lasers. Future technologic improvements anticipate even better treatments for patients with coronary artery disease. PMID- 7782675 TI - Pharmacologic therapy of angina pectoris. AB - The primary drugs utilized in the treatment of angina pectoris include organic nitrates, beta-adrenoceptor antagonists, Ca2+ antagonists, and the antithrombotic agents aspirin and heparin. Not all of these drugs are useful in every form of angina, and treatment is symptomatic rather than curative. In stable effort angina, beta-blockers, Ca2+ antagonists, and organic nitrates provide relief from angina pain and improve exercise tolerance primarily through their ability to decrease oxygen demand. The antiplatelet action of aspirin may decrease the incidence of myocardial infarction in these patients. Ca2+ channel blockers and organic nitrates are the drugs of choice for variant angina. These vasodilators restore blood flow by relieving the coronary vasospasm that triggers the ischemic episode. In unstable angina, aspirin and heparin reduce the risk of myocardial infarction, and aspirin increases survival. Heparin and nitrates alleviate angina pain, and under some circumstances beta-blockers and Ca2+ antagonists have a role in the relief of pain. PMID- 7782678 TI - The Birmingham mummy: the first torticollis in history. AB - The Birmingham Mummy is of a warrior, 25-35 years of age, from the Graeco-Roman period. He was struck from the front by an arrow, which penetrated the soft tissues of the neck to some depth and lodged in the right infratemporal fossa. It is suggested that the wound became infected and that muscle spasm induced the torticollis which was not fully corrected on mummification. PMID- 7782679 TI - A long-term review of the Shah Permavent tube. AB - A retrospective study of 74 Shah Permavent tube insertions is presented. These were inserted into 74 ears of 55 patients during the period between 1985 and 1988. At the time of review, 35 tubes had extruded spontaneously, 11 tubes had been removed for recurrent infections, 10 tubes had been removed electively and 10 tubes were still in situ. On examination of the ears approximately 12 months after the tubes had extruded, the overall rate of tympanic membrane perforation was 18.2 per cent. In ears in which the Permavent tube extruded spontaneously the perforation rate was 22.2 per cent. In ears which the tube was removed because of infection the perforation rate was 20.0 per cent. However in ears in which the tube was removed electively the perforation rate was zero. This finding has implications in the use and management of long-term ventilation tubes. PMID- 7782681 TI - Epithelial migration in open mastoidectomy cavities. AB - Twenty patients who had undergone open cavity mastoidectomy for chronic middle ear disease were selected for study. Following initial microscopic aural toilet, each cavity was painted in its medial aspect with a marker solution of Bonney's Blue dye. Each patient was assessed at weekly intervals for a minimum of three months following application of dye, and a photographic record made of the cavity. Information was also sought regarding the clinical behaviour of the mastoid cavities, with particular regard to degree of otorrhoea, and accumulation of debris. Migration of epithelium inferred by visible movement of dye occurred in 17 of the 20 mastoid cavities. In all these cases migration occurred in a medial to lateral direction, towards the exterior. In two cases there was no visible migration throughout the period of observation, and inspection after six months revealed the dye to be still present in the original position. Both these cases were of dry trouble-free cavities in which accumulation of debris did not appear to be a problem. This finding calls into question the assumption that clean trouble-free cavities are maintained by a satisfactorily functioning epithelial migration. In the four cavities which suffered from intermittent otorrhoea, epithelial migration occurred at a similar rate to that in dry cavities. PMID- 7782680 TI - Prevalence of eardrum pathology in a cohort born in 1955. AB - The aim of this study was to compare the prevalence of the different types of eardrum pathology in a cohort of adults not previously treated by grommet insertion with corresponding findings obtained in a cohort previously treated with grommet insertion. A cohort born in 1955 were invited to a screening examination including otomicroscopy. In the untreated cohort, retraction of Shrapnell's membrane was found in four per cent of the ears compared to 20 per cent in the cohort treated with grommets. Tensa pathology, including atrophy and myringosclerosis, was found in six per cent of the ears in the untreated cohort and in 17 per cent in the treated cohort. Normal eardrums were found in 91 per cent of the ears. Despite the increased awareness of secretory otitis, as well as the increased rate of surgical treatment, the prevalence of eardrum pathology seems to be increasing. The reasons for this are discussed. PMID- 7782682 TI - Hearing loss associated with weapons noise exposure: when to investigate an asymmetrical loss. AB - The air conduction thresholds in the right and left ears, and the interaural asymmetry of thresholds at 0.5, 1, 2, 3, 4 and 6 kHz were measured in a group of 225 soldiers exposed to a variety of weapon noise who were referred for assessment because of a deterioration in hearing on routine testing. At 0.5 and 1 kHz the threshold levels rarely exceeded 25 dB and the interaural asymmetry was 10 dB or less in 90 per cent of cases. The degree of hearing loss and interaural asymmetry increased as the frequency increased, with the average loss being significantly greater in the left ear at 2, 3, 4 and 6 kHz. Recommendations are made for the selection of cases of asymmetrical hearing loss exposed to weapon noise which require further investigation to exclude a retrocochlear cause or to define spurious hearing threshold levels. PMID- 7782683 TI - Nasal laser mucotomy (L-mucotomy) of the interior turbinates. AB - Eighty-seven patients who were treated by laser mucotomy (L-mucotomy) of the inferior turbinates were followed-up for one year. Patients presented for laser surgery because of one of the three following symptoms: sneezing, rhinorrhoea, or nasal obstruction. All of them had had prior conservative or surgical treatments for their symptoms without improvement in their complaints and/or quality of life. L-mucotomy is a simple procedure performed under local anaesthesia on an ambulatory basis. A controlled amount of tissue from the inferior turbinates is ablated with improvement in the symptoms, as reported by the patients one year after laser surgery. The procedure is easy to perform, there is no bleeding, it is painless and without complications, but it requires rather expensive surgical equipment. PMID- 7782684 TI - The management of sinogenic orbital complications. AB - The place of conservative treatment in sinogenic orbital complications has not been fully explained in the literature. The question that remains unresolved is- at which stage of the disease is surgery indicated? A study was undertaken in 240 patients with sinogenic orbital complications, to determine this. The patients were divided into three groups according to the stage of the disease as determined clinically: Group 1 (52 patients) with early stage disease, as detected by cellulitis only; Group 2 (76 patients) with intermediate stage, as detected by periorbital cellulitis and proptosis, but with full range of eye movement and unaltered vision; Group 3 (122 patients) with late stage disease, as detected by periorbital cellulitis and gross proptosis, with limitation of eye movement and altered vision. Group 1 and Group 2 patients were treated conservatively, with intravenous antibiotics and antral lavage. Group 3 patients were treated with intravenous antibiotics and surgery. External frontoethmoidectomy was performed in 31 (bilateral in two), ethmoidectomy in 91 (bilateral in five), sphenoidectomy in 15 and bilateral antral washout in all (122 patients). There was 100 per cent success with conservative treatment in Group 1 patients, whilst in Group 2 there was 98.6 per cent failure. The 75 patients in whom conservative treatment failed were successfully treated with surgery: frontoethmoidectomy was performed in 66 and ethmoidectomy in nine. In Group 3 patients, 100 per cent success was achieved with intravenous antibiotics and surgery. Sinogenic orbital complications can be treated conservatively and surgically, depending on the stage of the disease on presentation. Conservative treatment is only suitable for early complications, i.e. patients with periorbital cellulitis only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782685 TI - Lymph node and distant metastases in patients with sinonasal carcinoma. AB - A retrospective analysis of 34 cases of sino-nasal squamous cell or undifferentiated carcinoma in patients admitted between 1984 and 1992 was undertaken. Multimodality therapy incorporated radiation, surgery and chemotherapy. The five-year survival rate was 53 per cent. The local control rate was 82 per cent. Patients died of local failure (six), distant metastases (six), lymph node metastases (one) and other causes (three). Twenty-eight patients with local control were separated into groups: G1-2 (well and moderately differentiated) and G3-4 (poorly differentiated and undifferentiated) and evaluated to find the association between differentiation and metastasis. Lymph node metastasis was not related to the degree of differentiation. Distant metastasis was significantly related to the degree of differentiation (Fisher's exact test: p = 0.007). The result of the combination therapy is poor for patients with poorly differentiated or undifferentiated carcinoma because of distant metastases. Adjuvant chemotherapy may be necessary for them to prevent distant metastasis. PMID- 7782686 TI - Comparison between short-term and long-term post-operative evaluation of sleep apnoea after uvulopalatopharyngoplasty. AB - For a long time uvulopalatopharyngoplasty (UPPP) has been used to treat the obstructive sleep apnoea syndrome (OSAS). The diverse surgical effects, the inadequate understanding of operation effect consistency, the possibility of disease progression, and the few reported papers for long-term evaluation after UPPP aroused our interest in designing this study. Fifteen OSAS patients who had undergone UPPP with pre-operative, initial post-operative and long-term post operative polysomnographic studies were included in this study. Long-term post operative polysomnography was undertaken more than five years after surgery. The polysomnographic evaluations included respiratory disturbance index (RDI), duration of saturation SaO2 < 85 per cent (DOS), and the lowest O2 saturation (LOS). Amongst them, 10 patients with initial post-operative RDI reduction > 50 per cent were considered responders. In these responders, the long-term follow-up results of all three parameters showed improvement compared to the pre-operative data. In a comparison between the initial and long-term post-operative sleep study results, LOS and DOS showed no significant difference. However, the long term post-operative RDI result became significantly worse. More than 80 per cent of all cases had subjective symptomatic improvement in the long-term post operative evaluation. The subjective improvement after operation is not adequately correlated to the polysomnographic result. We suggest that long-term follow-up for patients after UPPP is necessary. PMID- 7782687 TI - Post intubation laryngeal sequelae in an intensive care unit. AB - The incidence, severity and pattern of post-intubation laryngotracheal sequelae in a 12 bed multidisciplinary intensive care unit (ICU) were assessed in this prospective study. One-hundred and fifty consecutive patients requiring intubation for more than 24 hours for various indications were studied. Evaluation of the larynx and trachea was done using a fibreoptic bronchoscope introduced through the endotracheal tube prior to elective extubation. Rigid bronchoscopy and direct laryngoscopy were performed in very small children and adults requiring tracheostomy. One-hundred and thirty-one (87.6 per cent) patients had visible laryngeal pathology in the immediate post-extubation period. Thirteen (8.6 per cent) had long term sequelae. A high incidence of long term sequelae was noted in patients with seizures (25 per cent) followed by patients with head injury (19 per cent). Steroid therapy failed to offer any significant protection but resulted in doubling of pulmonary sepsis. A grading system was adopted to classify acute laryngotracheal injury and a significant correlation was found between the presence of slough in the immediate post-extubation period and subsequent development of long term sequelae. There was also a significant correlation between a deeper insertion of the endotracheal tube and development subsequently of long term sequelae. The significance of these findings is discussed. PMID- 7782688 TI - A confidential comparative audit of stapedectomies: results of the Royal College of Surgeons of England Comparative Audit of ENT surgery 1994. AB - This paper presents the results of a national confidential comparative audit of stapedectomy: 185 operations by 28 consultants over a two-year period were retrospectively analysed. This included 10 revision procedures. Small fenestra stapedectomies accounted for 63 per cent of the total. Thirty-nine per cent of consultants operated on the second ear. Of the 168 stapedectomies in which the hearing change was known at six months, 87 per cent achieved improved hearing, eight per cent had no change and five per cent were worse. The overall complication rate was 30 per cent with a 'dead ear' rate of two per cent. PMID- 7782689 TI - Nasal septal surgery: is routine follow-up necessary? AB - An audit project was undertaken to appraise the outcome of 95 cases of septal surgery over a 12-month period, taking into account the subjective alteration of symptoms, appearances at anterior rhinoscopy and complications. Seventy-three patients (76.8 per cent) attended the follow-up clinic three to six months (median four months) after surgery. There was an improvement in short-term nasal breathing and in the clinical appearance of the septum in 84.9 and 96.9 per cent respectively; a complication rate of 10.9 per cent and an overall satisfaction rate of 81.3 per cent were also noted. These results support those of other reported series and suggest that routine follow-up of uncomplicated cases of septal surgery is unnecessary. PMID- 7782690 TI - The need for excessive dietary sodium chloride following tympanoplasty. AB - Loss of a single nerve function in the peripheral network responsible for taste perception is traditionally considered clinically insignificant. However, we report the case of a 27-year-old woman who experienced significant selective taste loss for salt after manipulation of the chorda tympani during tympanoplasty. This effect may be explained by disorder of the functional neuroanatomy of salty taste perception together with strong lateralization of mastication to the affected side in this patient. Recently described inhibition of cranial nerve IX by cranial nerve VII is hypothesized as contributing to the contradiction between this case and the commonly accepted role of the chorda tympani in taste perception. PMID- 7782691 TI - Nasal tuberculosis--an increasing problem? AB - Nasal tuberculosis represents a rare manifestation of infection by Mycobacterium tuberculosis: a case is presented together with a review of the literature. The correct management is documented, especially the need to treat the patients as if there was a generalized condition, and the problems concerning drug resistance are also considered. The incidence of this disease is rising and its importance must once again be highlighted. PMID- 7782692 TI - Treatment of Robin sequence with nasal CPAP. AB - A 12-year-old schoolgirl presented with severe obstructive sleep apnoea due to the Robin sequence. The sleep apnoea, together with the associated findings of daytime sleepiness, nocturia, right heart strain and growth retardation, were successfully reversed by nasal CPAP therapy. This therapy allows postponement of a decision concerning corrective surgery until after full growth has occurred. PMID- 7782693 TI - Airway obstruction with stridor due to nasal secretions. AB - Two cases of non-fatal airway obstruction by nasal secretions are described. The diagnosis was made after laryngoscopy and the features which suggested this previously undescribed aetiology were: depression of conscious level; poor oral hygiene; and irregular friable mass with mucoid areas obstructing the airway. The diagnosis was confirmed by histological examination of the obstructing material which was composed of laminated fragments of squamous epithelium, keratin debris and mucus. It is suggested that these masses form in the post-nasal space and then become dislodged descending into the larynx, where they cause partial laryngeal obstruction and stridor. In patients whose conscious level is depressed and who have poor oral hygiene, nasal secretions should be considered as a cause of sudden unexplained airway obstruction and stridor. PMID- 7782694 TI - An unusual presentation of an unusual complication of infectious mononucleosis: haematemesis and melaena. AB - Tonsillar haemorrhage is a rare complication of infectious mononucleosis. We present a case of life-threatening tonsillar haemorrhage secondary to infectious mononucleosis in a young man whose predominant symptoms at presentation were haematemesis and melaena. The origin of the haemorrhage was not obvious until the patient was examined under anaesthesia. The bleeding was controlled by emergency tonsillectomy. PMID- 7782696 TI - Supraglottic transection: results of repair and functional outcome. AB - We present two cases of supraglottic transection, with concomitant neurotemesis of the superior laryngeal nerve. Both cases were repaired primarily and a temporary tracheostomy was used to protect the airway. In both cases subsequent decannulation was achieved within four weeks, following the initial injury. No long-term swallowing or voice disturbance was noted in either case. We recommend that in such cases it is unnecessary to repair the nerves directly, but that careful repair of the wound itself will achieve a functional result. PMID- 7782695 TI - Candida epiglottitis in an adult with acquired immunodeficiency syndrome treated with oral fluconazole. AB - Candida epiglottitis has been reported in immunocompromised patients, but in only one paediatric patient with human immunodeficiency virus. We present possibly the first reported case of Candida infection of the epiglottis in an adult with human immunodeficiency virus treated with oral fluconazole. We review the symptoms, diagnosis, and management of the published cases of Candida epiglottitis in patients without the human immunodeficiency virus. Laryngoscopy and culture are diagnostic. PMID- 7782697 TI - Palatal pleomorphic adenoma in a child. AB - Benign salivary gland tumours in childhood are rare. We present a case of a pleomorphic adenoma arising in a minor salivary gland within the hard palate, review the literature and discuss the diagnostic and therapeutic features of the condition. PMID- 7782698 TI - Radiation-induced tumours of the head and neck. AB - In order to study the induction of malignancy in normal tissues due to ionizing radiation, we reviewed the files of 2500 patients with a tumour of the head and neck treated at the Netherlands Cancer Institute (Antoni van Leeuwenhoek Ziekenhuis), Amsterdam, from 1977 to 1993. We then checked whether or not these patients had been previously irradiated. Patients with a thyroid carcinoma or skin cancer were excluded from the study, since it is generally known that previous irradiation is a risk factor in these tumours. Eighteen patients were found to have a malignancy within a previously irradiated area (0.70 per cent). The mean interval between radiation and diagnosis of the head and neck tumour was 36.5 years. There were five soft tissue sarcomas, nine squamous cell carcinomas and four salivary gland tumours. Fourteen patients were operated upon whereas four received palliative treatment only. The median survival of the total group was 3.5 years. Particularly, in young patients because of the better cancer therapy and prolonged survival one must be aware of the increased risk of radiation-induced tumours. PMID- 7782699 TI - Case report: greatly enlarged jugular fossa with progressive sensorineural hearing loss. AB - A case of a five-year-old child with a greatly enlarged jugular fossa and high jugular bulb with associated progressive sensorineural hearing loss is presented. While various forms of this anatomical variant have been described by many authors, this is an extreme example, and progressive symptoms are most unusual. PMID- 7782701 TI - What a year! PMID- 7782700 TI - Lipomas of the larynx and hypopharynx: a review of the literature with the addition of three new cases. AB - Lipomas of the larynx and hypopharynx are uncommon mesenchymal neoplasms. This report discusses the clinical and pathological features of three cases of laryngeal and hypopharyngeal lipomas. Two of the cases occurred in females and one in a male. The ages of the patients were 28, 51 and 51 years respectively. Two of the cases involved the supraglottic larynx (left arytenoid and left vestibular fold); the third involved the pyriform sinus. Symptoms included airway obstruction, dysphagia, throat discomfort, a sensation of excessive secretions in the throat and an increase in snoring. The complaints occurred over periods ranging from several months to one year in duration. Clinically, a polypoid lesion described as yellow in appearance was seen. Histologically, the tumours were composed of mature adipocytes without evidence of pleomorphism, lipoblasts or infiltrative growth. Surgery was the treatment of choice and included simple but complete excision in two of the cases. In these two cases, surgery proved curative with follow-up periods of 11 and seven years, respectively. In one case, the initial tumour was removed in pieces. This lesion recurred 15 years after the initial resection and was totally excised at that time. This patient has been free of tumour for more than five years. PMID- 7782702 TI - Chiropractic politics. PMID- 7782703 TI - Medical care in Ukraine (Jan. 1995) PMID- 7782704 TI - MSAs: power to the patients. PMID- 7782705 TI - On epidemic diseases and public health. PMID- 7782706 TI - The "new tuberculosis" and its changing epidemiology. Nosocomial transmission and hospital discharge standards. PMID- 7782708 TI - Fear not science drives toxicologic risk assessment. PMID- 7782707 TI - Laboratory diagnosis of tuberculosis: past, present, and future. AB - Resurgence of tuberculosis justifies extraordinary efforts to expedite TB diagnosis and susceptibility testing. This demands that laboratory support expand to a "second generation" of methods and procedures, including rapid availability of fluorochrome smears of concentrated specimens, faster techniques for detection (e.g., the BACTEC radiometric broth system and microcolony detection), quicker identification (e.g., high-pressure liquid chromatography, nonisotopic genetic probes), more rapid susceptibility testing methods (e.g., BACTEC), and reporting of these results as critical values. Guidelines have been established for turnaround time for results of smears, TB organism identification, and susceptibility testing to usual first-line drugs. A "third generation" of laboratory techniques soon will make testing not only more effective but also more efficient. These methods include direct testing of respiratory specimens through nonisotopic genetic probes as well as nucleic acid amplification techniques utilizing polymerase chain reaction (PCR) and other molecular procedures. These new procedures and protocols place heavy demands on laboratory test volume, technologist time and costs. For the healthcare system or clinical laboratory without the resources to deal with these new demands, referral of TB specimens represents a reasonable alternative, as long as transport is adequate to meet current CDC and other guidelines for turnaround time. PMID- 7782709 TI - Environmental policy through a systems approach. PMID- 7782710 TI - Vertical integration: the next antitrust regulatory frontier. PMID- 7782711 TI - The resurgence of tuberculosis: a formidable foe. PMID- 7782712 TI - Health care reform: individual freedom or collectivism? PMID- 7782713 TI - The truth about Medicaid. PMID- 7782714 TI - Provider-assisted suicide: is it ethical? PMID- 7782715 TI - The final word: a new public health? PMID- 7782716 TI - Ingestive sensory inputs excite serotonin effector neurones and promote serotonin depletion from the leech central nervous system and periphery. AB - Thermal and chemical stimuli known to promote ingestive behaviours in the medicinal leech Hirudo medicinalis were tested for their physiological effects on Retzius neurones and for their biochemical effects on serotonin levels in the central nervous system, pharynx and body wall. Retzius neurones throughout the leech nerve cord receive excitatory synaptic input during thermal or chemical stimulation of the prostomial lip. These neurones respond to the rate of change of temperature as well as to absolute temperature at the lip. Exposure of the lip to sodium chloride excites Retzius neurones, whereas exposure to arginine has little effect. Thermal stimulation of the lip elicits a more rapid but less prolonged excitation of Retzius neurones than does chemical stimulation. Stimulation of the prostomial lip is associated with afferent activities in the cephalic nerves D1, D2 and V1-2. Thermal stimulation of the prostomial lip results in depletion of serotonin from midbody ganglia, whereas chemical stimulation has no effect. Conversely, chemical stimulation of the lip results in depletion of serotonin from the body wall, whereas thermal stimulation does not. Pharyngeal serotonin content is decreased with either modality. These data distinguish two important feeding-related sensory input pathways to central serotonergic effector neurones in Hirudo medicinalis. PMID- 7782717 TI - Hindleg muscle energy and substrate balances in cold-exposed rats. AB - Rats chronically cannulated in the carotid artery and the muscular branch of the femoral vein were subjected to a cold (4 degrees C) environment for up to 2 h. The changes in blood flow (measured with 46Sc microspheres) and arterio-venous differences in the concentrations of glucose, lactate, triacylglycerols and amino acids allowed the estimation of substrate (and energy) balances across the hindleg. Mean glucose uptake was 0.28 mumol min-1, mean lactate release was 0.33 mumol min-1 and the free fatty acid basal release of 0.31 mumol min-1 was practically zero upon exposure to the cold; the initial uptake of triacylglycerols gave place to a massive release following exposure. The measurement of PO2, PCO2 and pH also allowed the estimation of oxygen, CO2 and bicarbonate balances and respiratory quotient changes across the hindleg. The contribution of amino acids to the energy balance of the hindleg was assumed to be low. These data were used to determine the sources of energy used to maintain muscle shivering with time. Three distinct phases were observed in hindleg substrate utilization. (1) The onset of shivering, with the use of glucose/glycogen and an increase in lactate efflux. Lipid oxidation was practically zero (respiratory quotient near 1), but the uptake of triacylglycerols from the blood remained unchanged. (2) A substrate-energy shift, with drastically decreased use of glucose/glycogen, and of lactate efflux; utilization of triacylglycerol as practically the sole source of energy (respiratory quotient approximately 0.7); decreasing uptake of triacylglycerol and increased tissue lipid mobilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782718 TI - Adipokinetic hormone stimulates neurones in the insect central nervous system. AB - A simple preparation designed to screen and compare the central action of putative neuroactive agents in the moth Manduca sexta is described. This approach combines microinjections into the central nervous system with myograms recorded from a pair of spontaneously active mesothoracic muscles. Pressure injection of either octopamine or Manduca adipokinetic hormone (M-AKH) into the mesothoracic neuropile increases the monitored motor activity. Under the conditions used, the excitatory effects of M-AKH exceed those of the potent neuromodulator octopamine. This suggests that M-AKH plays a role in the central nervous system in addition to its known metabolic functions and supports recent evidence that neuropeptides in insects can be multifunctional. PMID- 7782719 TI - Adaptive responses to feeding in Burmese pythons: pay before pumping. AB - Burmese pythons normally consume large meals after long intervals. We measured gut contents, O2 consumption rates, small intestinal brush-border uptake rates of amino acids and glucose, organ masses and blood chemistry in pythons during the 30 days following ingestion of meals equivalent to 25% of their body mass. Within 1-3 days after ingestion, O2 consumption rates, intestinal nutrient uptake rates and uptake capacities peaked at 17, 6-26 and 11-24 times fasting levels, respectively. Small intestinal mass doubled, and other organs also increased in mass. Changes in blood chemistry included a 78% decline in PO2 and a large 'alkaline tide' associated with gastric acid section (i.e. a rise in blood pH and HCO3- concentrations and a fall in Cl- concentration). All of these values returned to fasting levels by the time of defecation at 8-14 days. The response of O2 consumption (referred to as specific dynamic action, SDA) is the largest, and the upregulation of intestinal nutrient transporters the second largest, response reported for any vertebrate upon feeding. The SDA is a large as the factorial rise in O2 consumption measured in mammalian sprinters and is sustained for much longer. The extra energy expended for digestion is equivalent to 32% of the meal's energy yield, with much of it being measured before the prey energy was absorbed. PMID- 7782720 TI - An endogenous peptide modulates the activity of a sensory neurone in the leech Hirudo medicinalis. AB - Sensory and neurosecretory innervation of each leech excretory complex, a nephridium and its bladder, is accomplished by a single neurone, the nephridial nerve cell (NNC). The NNC monitors the extracellular Cl- concentration, which ranges between 20 and 100 mmol l-1 depending on the physiological state. The NNC contains FMRFamide in its soma and sensory terminals in the nephridium. Bath or focal application of FMRFamide leads to hyperpolarization and decreases the rate of firing of the NNC, suggesting autoregulation of peptide release. Experiments under single-electrode current-clamp and voltage-clamp show that FMRFamide turns off the receptor-specific Cl- current of the NNC, indicating that FMRFamide also modulates the receptor gain. PMID- 7782722 TI - Haematocrit and cardiovascular risk. PMID- 7782721 TI - Ventilatory responses to carboxyhaemoglobinaemia and hypoxic hypoxia in Bufo paracnemis. AB - The modality of the O2 drive to breathe was evaluated in unanaesthetized Bufo paracnemis. Carbon monoxide (CO) hypoxia was applied to reduce CaO2 (arterial O2 content). Arterial PO2 (PaO2) was reduced through inspiration of hypoxic gas mixtures (hypoxic hypoxia). Measurements included pulmonary ventilation, CaO2, PaO2, pHa, blood pressure and heart rate. Application of fractional concentrations of CO equivalent to 0.001 reduced CaO2 from 11.6 +/- 1.2 to 8.6 +/ 0.7 vol% (mean +/- S.E.M., N = 6) without any effect on heart rate, blood pressure or ventilation. Inspiration of fractional concentrations of CO equivalent to 0.01 reduced CaO2 to 5.1 +/- 0.7 vol%, which was accompanied by increased ventilation. This response, however, correlated with a decreased arterial pH. The effect of a fractional concentration of CO of 0.01 on ventilation was abolished by compensation of pH through bicarbonate infusion. Consequently, carboxyhaemoglobinaemia per se failed to increase ventilation. By contrast, reductions of PaO2 clearly stimulated ventilation, which indicates that O2 partial pressure provides the principal O2 stimulus to breathe in Bufo paracnemis. PMID- 7782723 TI - Apoptosis: molecular mechanisms and implications for human disease. AB - Apoptosis is a highly regulated process of cell death with characteristic morphological changes that are distinct from necrosis. The biochemical machinery responsible for apoptotic cell death appears to be constitutively expressed in most, if not all, cells and can be triggered by a variety of signals, including sustained increases in the intracellular Ca2+ level. Apoptosis is the main mechanism of cell deletion during development, normal cell turnover, hormone induced tissue atrophy, and pathological processes such as T-cell depletion in HIV/AIDS and neurodegenerative disease. The aim of this review is to briefly summarize current knowledge of the molecular mechanisms of apoptosis and its role in human disease. PMID- 7782724 TI - Fasting blood glucose in determining the prevalence of diabetes in a large, homogeneous population of Caucasian middle-aged women. AB - OBJECTIVES: To determine the usefulness of a single, fasting blood glucose (FBG) value in measuring the prevalence of diabetes mellitus in a large, homogeneous population. DESIGN: Fasting blood glucose and 2-h oral glucose tolerance test (OGTT) values were determined. Based on the results of the OGTT, the sensitivity and specificity of different cut-off levels of FBG for the diagnosis of diabetes were assessed. ROC (receiver operating characteristic) analysis was performed on the data. SETTING: A health screening unit at the University Hospital in Malmo, Sweden. SUBJECTS: A total of 1843 Caucasian women without known diabetes aged 55 57 years. RESULTS: The prevalence of previously undiagnosed diabetes was 3.9% and the prevalence of impaired glucose tolerance (IGT) was 27.9% using the WHO cut off values for 2-h blood glucose values after an OGTT. With an FBG cut-off value of 6.7 mmol L-1, the sensitivity of a single FBG value was 36.6%. Reducing the cut-off value to 6.0 mmol L-1 increased the sensitivity to 53.4%. At a cut-off level of 4.8 mmol L-1, the sensitivity reached the high value of 85.9%, but the specificity was only 45% and the predictive value of a positive test as low as 5.9%. ROC analysis showed that the optimal cut-off value for FBG in this population was 5.3 mmol L-1, giving a sensitivity and specificity of 77% but a positive predictive value of only 11.9%. CONCLUSIONS: This study has shown that in a large and homogeneous Caucasian population of women aged 55-57 years with a high prevalence of IGT, a single FBG value is not useful as a screening tool for diabetes mellitus. PMID- 7782725 TI - Diterpene composition of oils from Arabica and Robusta coffee beans and their effects on serum lipids in man. AB - OBJECTIVES: The cholesterol-raising effect of boiled coffee is caused by diterpenes from coffee oil. In order to identify the diterpene responsible, we analysed the diterpene composition of oils from Arabica (Coffea arabica) and Robusta (Coffea canephora robusta) beans and their effects on serum lipids and thyroid function. DESIGN, SUBJECTS, AND INTERVENTION: During the first 3-week period of a randomized, cross-over trial, 11 healthy, normolipaemic volunteers received per day either 2 g of coffee oil (n = 5) or placebo oil (n = 6). After a 2-week wash-out, the reverse treatments were applied for another 3 weeks. Six subjects received Arabica oil, supplying 72 mg day-1 cafestol and 53 mg day-1 kahweol, and five received Robusta oil, which provided 40 mg of cafestol, 19 mg of 16-O-methyl-cafestol, and 2 mg of kahweol per day. Background diets were constant. RESULTS: The average serum cholesterol levels rose by 0.65 mmol L-1 (13%) on Arabica oil (P < 0.025; 95% CI, 0.21-1.09 mmol L-1) and by 0.53 mmol L-1 (13%) on Robusta oil (NS; 95% CI -0.36-1.42 mmol L-1). The triglycerides levels rose by 0.54 mmol L-1 (71%) on Arabica (P < 0.005; 95% CI, 0.22-0.76 mmol L-1) and 0.49 mmol L-1 (61%) on Robusta oil (P < 0.005; 95% CI, 0.30-0.68 mmol L-1). None of the effects on serum lipids or lipoprotein cholesterol levels was significantly different between Arabica and Robusta oil. Concentrations of serum total and free thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were largely unaffected. CONCLUSIONS: Both Arabica and Robusta oil elevated serum lipid levels; therefore, cafestol must be involved and kahweol cannot be the sole cholesterol-raising diterpene. The mode of action of coffee diterpenes does not involve induction of hypothyroidism. PMID- 7782726 TI - Diminished vitamin B12 levels in patients with severe sickle cell disease. AB - OBJECTIVE: The aim of this study was to estimate the levels of vitamin B12 in patients with severe sickle cell disease compared to normal controls. Complete blood count, iron studies and vitamin B12 levels were obtained in 85 consecutive patients with severe sickle cell disease (56 males, 29 females, aged 14-49 years) and 100 healthy blood donors (67 males, 33 females, aged 17-60 years) as a normal control group. RESULTS: Thirty-seven of the 85 patients (43.5%) had serum vitamin B12 levels below normal values (mean 84.3 +/- 28.7, range 7-145 pmol L-1) without macrocytosis or hypersegmented neutrophils. The mean level of vitamin B12 in the remaining 48 patients (56.5%) was normal (mean 233.3 +/- 73.9, range 152-435 pmol L-1) which is below the mean of normal control levels (mean 327.7 +/- 168.7, range 178-897 pmol L-1). Patients with low B12 achieved a significant symptomatic improvement when treated with vitamin B12, 1 mg intramuscularly weekly for 12 weeks when compared with patients with normal B12 levels. CONCLUSION: We conclude that many patients with severe sickle cell disease may suffer from unrecognized vitamin B12 deficiency. PMID- 7782727 TI - von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long-term compliance with a lipid-lowering diet. AB - OBJECTIVES: To test whether serum von Willebrand factor (vWf) would be lower in men with atherosclerosis who had been consuming a lipid-lowering diet for 3 years than in a control group of men with atherosclerosis who had been following their normal diet. DESIGN: A randomized, population-based case-control study. SETTING: A tertiary health care referral centre at a University Hospital. SUBJECTS: Men age less than 66 years with angiographically proven coronary atherosclerosis and a cholesterol level > 6 mmol L-1. Sixty started the study and 50 completed it. INTERVENTIONS: Subjects were randomized to a lipid-lowering diet or to taking their normal diet for approximately 3 years. MAIN OUTCOME MEASURES: The components of the subjects' diets were assessed and blood was obtained for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and for vWf. RESULTS: Men on the lipid-lowering diet consumed less total, saturated and monounsaturated fats (all P < 0.001), cholesterol and retinol (both P < 0.002) but increased polyunsaturated fats (P < 0.001), fibre, vitamin E (both P < 0.005) and carbohydrate (P < 0.05). Those on the lipid lowering diet also had lower serum levels of total and LDL cholesterol (P < 0.002 and P < 0.05, respectively), triglycerides (P < 0.02) and vWf (P < 0.05) than the men on their normal diet. There was no difference in HDL cholesterol. Levels of vWf correlated with both total cholesterol (P < 0.005) and inversely with dietary polyunsaturated fats (P < 0.02). CONCLUSION: von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long-term compliance with a lipid-lowering diet. PMID- 7782728 TI - Left ventricular thrombosis after anterior myocardial infarction with and without thrombolytic treatment. AB - OBJECTIVES: To examine the incidence of left ventricular thrombus in patients with anterior myocardial infarction, with and without streptokinase treatment. To identify predictors of thrombus development. DESIGN: Consecutive patients prospectively studied during the hospitalized period. Echocardiography was performed within 3 days of admission and before discharge. SETTING: Umea University Hospital, a teaching hospital in Northern Sweden. SUBJECTS: Ninety nine patients with anterior myocardial infarction of whom 74 were treated with streptokinase. MAIN OUTCOME MEASURES: Left ventricular thrombus and left ventricular segmental myocardial function. RESULTS: During the hospital stay, a thrombus developed in 46% (95% confidence interval [CI], 35-57%) of the patients in the thrombolysis group and in 40% (95% CI, 21-59%) of the patients in the non thrombolysis group. No difference in left ventricular segmental myocardial function was found between the thrombolysis and non-thrombolysis groups at hospital discharge. No embolic events were observed. The occurrence of a left ventricular thrombus at hospital discharge was significantly associated with previous myocardial infarction, peak enzyme levels, left ventricular global and segmental dysfunction and an increased dose of peroral diuretics or use of parenteral diuretics. In a multiple logistic regression model, left ventricular segmental dysfunction was the most important predictor of left ventricular thrombus. CONCLUSION: Thrombolytic treatment with streptokinase does not prevent the development of a left ventricular thrombus but the risk of embolic complications is low. The left ventricular segmental myocardial score can be used to assess the risk of thrombus development, also, after thrombolysis. PMID- 7782729 TI - Impaired melatonin secretion in patients with Wernicke-Korsakoff syndrome. AB - OBJECTIVES: Melatonin (MT) undergoes circadian changes in response to external light conditions and has been implicated in the control of other circadian hormone variations. Alcohol inhibits MT secretion in healthy subjects. The purpose of the present investigation was to elucidate whether patients with Wernicke-Korsakoff syndrome (WKS) also have impaired MT secretion after a period of prolonged alcohol abstention. If so, it would be of interest to find out whether this affects cortisol rhythmicity. DESIGN: Seven patients with WKS and 8 healthy controls were included in the study. Venous blood was sampled every 2nd h between 18.00 and 08.00 hours, and urine collected between 22.00 and 07.00 hours. SETTING: Department of Internal Medicine, Endocrinology Section, Sodersjukhuset, Stockholm. MAIN OUTCOME MEASURES: Peak serum MT values during the night, total nocturnal MT secretion (estimated by MT incremental areas), and urinary excretion of MT were determined in each participant. Serum cortisol levels were determined in the patients at 18.00, 02.00 and 08.00 hours. RESULTS: Patients with WKS had a markedly reduced nocturnal secretion of MT compared to healthy volunteers (MT incremental areas 0.33 +/- 0.21 vs. 1.60 +/- 0.29 nmol L-1 h-1, mean +/- SEM; P < 0.005). Amongst the patients, the serum cortisol level was higher in the morning than in the afternoon (331 +/- 46 vs. 240 +/- 52 nmol L-1; P < 0.01), and showed a nadir during the night (138 +/- 45 nmol L-1) as in normal individuals. CONCLUSION: Patients with WKS have markedly reduced nocturnal secretion of MT. The exact mechanism behind this finding has to be further elucidated. However, it is of interest to note that despite the lack of clearcut circadian MT changes. WKS patients retain normal cortisol secretion, thus suggesting that MT rhythm may not be obligatory for the proper control of circadian cortisol rhythmicity. PMID- 7782730 TI - Habitual diet, platelet function, fibrinogen and factor VII coagulant activity in young Finns. AB - OBJECTIVES: The objective of the study was to determine whether an association between diet and platelet function, plasma fibrinogen level and factor VII coagulant activity (VII:C) could be established in young subjects. DESIGN: Data on the habitual diet of the subjects were collected either by a questionnaire on food habits (n = 204) or by a 48-h dietary recall interview (n = 53). SUBJECTS: The subjects were participants in the project 'Cardiovascular Risk in Young Finns' (age range 15-30 years). A total of 204 subjects having a questionnaire on food habits participated in the platelet function tests and 53 also participated in a 48-h dietary recall interview. Plasma fibrinogen concentration and factor VII: C were measured from 79 subjects. MAIN OUTCOME MEASURES: Platelet function was tested by turbidometric measurement of platelet aggregation using ADP and collagen as aggregation agents. RESULTS: Platelet aggregation with ADP (at up to 4.0 mumol L-1) and collagen (at up to 5.0 micrograms mL-1 platelet-rich plasma PRP) showed that the diet characterized as 'saturated', i.e. containing high-fat milk and saturated fat, was associated with platelets less sensitive to aggregating agents in vitro when compared to the unsaturated type of diet. Collagen- but not ADP-induced aggregation decreased with age of the subjects (P = 0.026-0.057, regression coefficient). An inverse regression coefficient between plasma factor VII:C (101%; range 64-145%) and serum triglycerides (P = 0.006) and the intake of rye (g 1000 kcal-1; P = 0.03) were found. CONCLUSIONS: In this study we showed that platelet reactivity and factor VII:C already differ considerably between subjects at a young age, and diet may explain some of this variation. PMID- 7782732 TI - Liberalized diet in patients with type 1 diabetes. AB - OBJECTIVE: To document that strict dietary regimen are not necessary in the context of intensified insulin therapy. DESIGN: German multicentre, prospective cohort study; 6 years follow-up. SETTING: Ambulatory examination using a mobile ambulance. SUBJECTS: A total of 636 type 1 diabetic patients (age 33 +/- 7 years, diabetes duration 15 +/- 7 years; mean +/- SD), who had participated in a structured, 5-day, in-patient, group treatment and teaching programme for intensification of insulin therapy and liberalization of the diabetes diet 6 years prior to follow-up. MAIN OUTCOME MEASURES: Relations between the extent to which patients practise a liberalized diet, the degree of metabolic control (HbA1c, severe hypoglycaemia, body mass index, cholesterol), and the patients' perceived burden through dietary treatment. RESULTS: In the total patient group, HbA1c was 7.9 +/- 1.6%, and the incidence of severe hypoglycaemia was 0.17 cases per patient during the preceding year; 31% patients injected insulin < or = 3 times per day, 58% 4-7 times per day, and 11% used insulin pump therapy. Only 11% patients reported following a meal plan, whereas 89% continually changed timing and amount of carbohydrate intake; only 5% had the same number of meals every day, whereas as many as 20% varied the number of meals per day by four or more; 53% skipped main meals; 85% habitually consumed sugar or sugar containing foods. Patients with a higher degree of diet liberalization injected insulin or used an insulin pump therapy more frequently, and perceived their dietary treatment to be less burdensome. No clinically significant associations were found between the extent of diet liberalization and metabolic control. CONCLUSIONS: Under the conditions where type 1 diabetic patients have the opportunity to participate in an intensified insulin treatment and teaching programme, liberalization of the diabetes diet is not associated with adverse effects on glycaemic control, but is associated with less perceived burden through dietary treatment. PMID- 7782731 TI - Incidentally detected adrenal tumours (incidentalomas): histological heterogeneity and differentiated therapeutic approach. AB - OBJECTIVES: To find a differentiated therapeutical approach to incidentalomas. DESIGN: Prospective study of incidentalomas: their histology, hormonal activity, and growth if primarily non-operated. SETTING: Admissions to an academic tertiary care centre because of incidentaloma. PATIENTS: Thirty-eight female, 25 male, 27 85 years old. INTERVENTIONS: Ultrasound, computed tomography and adrenal scintigraphy when appropriate; investigations to exclude malignancy giving metastasis into the adrenal gland; ACTH, cortisol, aldosterone, renin activity, androgene, catecholamine measurements; surgery or follow-up. MAIN OUTCOME MEASURES: Rate of malignancy; linkage of tumour size to probability of malignancy; prevalence of tumours with subtle hormone excess. RESULTS: Cortical adenomas occurred in 13/31, metastases in 7/31 of the histologically confirmed cases. In 10/31 cases, the computed tomography indicated a size that was smaller than the pathological size (mean = 20 mm). 20.6% of all incidentalomas and 61.5% of the 13 operated corticol adenomas showed subtle hormonal activity. Twenty seven incidentalomas < 30 mm were followed-up (3-41 months; mean 18 months) and showed growth in only one case. Sensitivity, specificity, and predictive value (PV) of a tumour > or = 30 mm to indicate malignancy were: 1.0, 0.56 and 0.27, respectively. The PV of a < 30 mm tumour to exclude malignancy was 1.0. CONCLUSIONS: Oncological screening tests are necessary in all incidentalomas. Tumours > or = 30 mm should be operated but smaller ones can be followed-up, because they are usually benign and rarely show progressive growth. Cortical adenomas with subtle hormonal overproduction and hypertension, diabetes or osteoporosis should be operated, irrespective of their size, but in the absence of relevant clinical symptoms they can be followed-up. PMID- 7782733 TI - Membranous glomerulonephritis associated with testicular seminoma. AB - Proteinuria, often nephrotic in range, is a recognized paraneoplastic syndrome of solid tumours, with membranous glomerulonephritis (MGN) the most common histopathological lesion seen on renal biopsy. A 56-year-old male was found to have proteinuria on routine medical examination. History, physical and serological evaluation failed to reveal an aetiology and subsequent renal biopsy showed MGN, presumed to be idiopathic. Prednisone therapy was begun but this proteinuria did not resolve (> 1 g 24 h-1). Eleven months later the patient discovered a testicular mass which was found to be a stage I seminoma upon excision and metastatic evaluation. His proteinuria rapidly normalized after orchectomy and regional lymph node radiotherapy. This is the first known case of MGN associated with testicular seminoma. PMID- 7782734 TI - Danazol in the treatment of endometriosis and hereditary angio-oedema. PMID- 7782735 TI - The special role of rimes in the description, use, and acquisition of English orthography. AB - The links between spellings and sounds in a large set of English words with consonant-vowel-consonant phonological structure were examined. orthographic rimes, or units consisting of a vowel grapheme and a final consonant grapheme, had more stable pronunciations than either individual vowels or initial consonant plus-vowel units. In 2 large-scale studies of word pronunciation, the consistency of pronunciation of the orthographic rime accounted for variance in latencies and errors beyond that contributed by the consistency of pronunciation of the individual graphemes and by other factors. In 3 experiments, as well, children and adults made more errors on words with less consistently pronounced orthographic rimes than on words with more consistently pronounced orthographic rimes. Relations between spellings and sounds in the simple monomorphemic words of English are more predictable when the level of onsets and rimes is taken into account than when only graphemes and phonemes are considered. PMID- 7782736 TI - Toward unbiased measurement of conscious and unconscious memory processes within the process dissociation framework. AB - L.L. Jacoby's (1991) process dissociation framework has been welcomed as a tool for differentiating controlled and automatic cognitive processes. Several variants of the original process dissociation measurement model are integrated in this article, and it is shown that the model ignores guessing and, hence, response bias. An extension of the original model is suggested that includes guessing parameters. The original model and the extended model are evaluated empirically. In 3 experiments using a yes-no recognition task, response bias was manipulated in various ways. The original model falsely attributes effects of response biases to either controlled or uncontrolled processes or to both. The extended model, in contrast, results in estimates of the contributions of controlled and uncontrolled memory processes that are relatively unaffected by response biases. The extended model is recommended as a measurement tool. PMID- 7782737 TI - The role of forensic anthropology in the recovery and analysis of Branch Davidian Compound victims: recovery procedures and characteristics of the victims. AB - Anthropological contributions to the investigation of the events at the Branch Davidian Compound near Waco, Texas in early 1993, were of two major types: the recovery of human remains from the site and the analysis of most of those individuals at the Medical Examiner's Office in Fort Worth, Texas. This paper describes the role of forensic anthropology in the recovery and analysis of Branch Davidian Compound victims and the recovery procedures and characteristics of the victims. PMID- 7782738 TI - The role of forensic anthropology in the recovery and analysis of Branch Davidian Compound victims: techniques of analysis. AB - The recovery and analysis of human remains from the Branch Davidian Compound, Mount Carmel, Texas, was a multidisciplinary team effort. This presentation deals with one aspect of the forensic anthropological contribution to this collaborative endeavor--the examination and inventory of human skeletal remains and the interpretation of these osteological data. Briefly described first are the content and format of the skeletal inventory and the examination procedures used for data collection. Two subsequent sections illustrate the use of these data to determine (a) age, sex, ancestry, stature, and other distinguishing characteristics, and (b) the presence and nature of any premortem, perimortem, and postmortem trauma. The next section shows how these findings assist in establishing positive identification through, for example, comparison with medical, dental, and other background records, especially comparison of premortem and postmortem radiographs of bones or dentition. In this context, we consider also the sorting of commingled remains, which includes preliminary assessment of rapidly decomposing remains prior to autopsy to preserve information crucial to identification. PMID- 7782739 TI - Forensic DNA testing on skeletal remains from mass graves: a pilot project in Guatemala. AB - A reliable method for extracting DNA from teeth was developed and successfully applied to a set of 12 skeletons recovered from two 10-year-old Guatemalan mass graves. Attempts to identify the remains by mitochondrial DNA (mtDNA) testing were hampered by low sequence diversity. Our findings demonstrate the feasibility of using DNA typing to identify victims from mass graves. PMID- 7782740 TI - Decomposition of buried human bodies and associated death scene materials on coral atolls in the tropical Pacific. AB - The decomposition of bodies and the decay of associated cultural materials, including clothing, personal ornaments, caskets, and grave goods, was investigated based on a series of exhumations on a small sand island on Kwajalein Atoll, Marshall Islands. Decay data were documented for an interment period between 40 and 80 months. PMID- 7782741 TI - Carbon monoxide-related deaths from 1984 to 1993 in Vienna, Austria. AB - Carbon monoxide poisoning occurs frequently in industrialized countries. Between 1970 and 1978 in Vienna, the capital of Austria, carbon-monoxide-rich coal gas was replaced with natural gas. Despite this fact, people still die of unintentional carbon monoxide poisoning. The main purpose of this study was to determine the reasons for unintentional carbon monoxide-related deaths, and further to describe the epidemiology of these fetal poisonings in Vienna between 1984 and 1993. A secondary purpose was to investigate whether intentional carbon monoxide poisoning still plays a role among suicides as was the case up to the 1970s. For this purpose we analyzed carbon monoxide-related deaths in Vienna from 1984 to 1993, based on actual autopsy reports of postmortems performed at the Viennese Institute of Forensic Medicine. Deaths due to fire were excluded. The main reason for unintentional carbon monoxide-related deaths in Vienna between 1984 and 1993 was flueless gas-fueled water heating appliances, overused especially by old people during the cold period of the year. The frequency of unintentional carbon monoxide-related deaths in 1993 was almost as high as in 1984. A total of 53% of deceased persons were over age 60. Most fatal carbon monoxide poisoning occurred during the cold period of the year. Suicides decreased significantly during the investigation period. In 76% of these deaths car exhaust fumes were inhaled, especially by men. In conclusion, we recommend programs to prevent unintentional carbon monoxide-related deaths. These programs should especially target the elderly. Flueless gas boilers should not be overused. Furthermore, apartments should be aired sufficiently, even during the cold period of the year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782742 TI - Forensic implications of biochemical differences among geographic populations of the black blow fly, Phormia regina (Meigen). AB - Cuticular hydrocarbons were extracted from individual adult blow flies from three geographic populations of Phormia regina from areas near Tucannon River and Lyle Grove, Washington, and from Rensselaer, Indiana. The individual extracts were subjected to gas chromatography/mass spectrometry (GC/MS), and 22 hydrocarbons were identified. Discriminant analysis of the cuticular hydrocarbon profiles separated the flies according both to location and gender. These results have potential forensic applications in the determination of corpse relocation and in the study of the population ecology of species and populations. PMID- 7782743 TI - Does drug abuse lead to criminal behavior? An analysis based on criminal registers of 117 drug-related deaths, examined in 1992 at the Institute of Forensic Medicine in Vienna, Austria. AB - That there is a link between drug abuse and criminal behavior has been established. However, explaining the nature of this relationship has proven difficult. The purpose of this study was to investigate whether the traditional view that drug abuse leads to future criminal behavior holds true in case of the drug-related deaths examined in 1992 at the Institute of Forensic Medicine in Vienna, Austria. For this purpose postmortem reports and criminal registers of 117 drug-related deaths were analyzed. A total of 43% of the examined sample had no criminal register. Regarding age at time of death there was no difference between those with or without a criminal register. A total of 57% had at least one conviction. A minority committed about one third of offenses. Property offenses were the most frequent type. Those who started their criminal history with a property offense were younger at time of first conviction and committed more offenses during their life. In summary, the traditional view that drug abuse leads to future criminal behavior does not seem to hold true in case of the drug related deaths examined in 1992 at the Institute of Forensic Medicine in Vienna, Austria. The results of this retrospective study speak in favor of a view that drug abuse may be a part of contemporary delinquent behavior, rather than the cause of criminality. PMID- 7782744 TI - Postmortem drug metabolism by bacteria. AB - Studies were undertaken to determine the possible role of enteric bacteria in the postmortem bioconversion of the nitrobenzodiazepines flunitrazepam, clonazepam, and nitrazepam. Flunitrazepam, clonazepam, and nitrazepam were completely metabolized in blood in the presence of eight species of enteric bacteria to their respective 7-amino-metabolites. The rates of metabolism, at 37 degrees C, ranged from 0.1 ng/mL/min for Streptococcus faecalis to 8.8 ng/mL/min for Clostridium perfringens. The rate of conversion was reduced to 87% by a combination of 0.7% (w/v) sodium fluoride and potassium oxalate, and almost completely inhibited (96%) by 1% (w/v) sodium fluoride. pH had variable effects on the rate of metabolic bioconversion of nitrobenzodiazepines, while increasing temperatures were found to generally increase the rate of nitrobenzodiazepine bioconversion. These data support the proposal that bacteria may mediate postmortem bioconversion of the nitrobenzodiazepines. PMID- 7782745 TI - Cocaine, opiates, and ethanol in homicides in New York City: 1990 and 1991. AB - Studies using medical examiner cases are useful in monitoring drug use in special populations. This study assesses the presence of cocaine and its metabolite, benzoylecgonine (BE), opiates and ethanol in all homicide victims who were injured and who survived two hours or less after injury in 1990 and 1991 in New York City. There were 2824 homicides in the study period and cocaine and/or BE were found in 884 (31.3%) of cases. In over half of the cases positive for cocaine/BE, ethanol or opiates were found. African-Americans and Latinos were much more likely than whites or Asians to be positive for cocaine/BE. There were no differences between men and women in regard to being positive for cocaine/BE. Cocaine/BE was most frequently identified among victims 25 to 44 years of age. Males were more likely to be positive for ethanol. There were no differences among age groups or ethnic groups in regard to ethanol except for a very low ethanol incidence among Asians. Victims positive for cocaine/BE were more likely to be killed with firearms in open places. The percentage of victims positive for cocaine/BE remains approximately that found by other studies in the late 1980s, however, the percentage of opiate-positive homicides seems to be increasing. Opiates usually were found with cocaine/BE. Two-thirds of the cocaine and/or BE positive cases had cocaine present, thus they were under the influence of the drug at the time they were injured. The authors discuss how the use of cocaine, ethanol and opiates may be related to one's becoming a homicide victim. PMID- 7782746 TI - Validation of the AmpliFLP D1S80 PCR Amplification Kit for forensic casework analysis according to TWGDAM guidelines. AB - The validation of the AmpliFLP D1S80 PCR Amplification Kit for use in forensic casework was accomplished by performing all the relevant experiments outlined in the TWGDAM guidelines. Standard specimen and reproducibility studies were performed using organic and rapid DNA extraction techniques on both stain and liquid samples (blood, semen and saliva). Over 300 samples from three different populations (US Caucasians, African Americans and US Hispanics) were analyzed to determine allele and genotype frequencies. Purified DNA was mixed in defined ratios (ranging from unmixed DNA samples to 1:9 mixtures of 2 different DNA samples) prior to amplification to demonstrate that samples containing DNA from more than one individual can be detected and, in many cases, that the genotypes contributing to the mixture can be identified. Since casework samples frequently are exposed to environmental insults that can result in DNA degradation, purified DNA was degraded in the laboratory to analyze the effect of DNA fragment length on D1S80 amplification. It is crucial in the validation process to examine actual casework evidentiary material. This D1S80 kit can be used successfully by forensic scientists to amplify and type nonprobative evidentiary material, including bloodstains collected from crime scenes and rape kit materials collected for sexual assault cases. The D1S80 kit is specific to human DNA, and the D1S80 alleles are inherited according to the laws of Mendel. The sensitivity of the novel gel electrophoresis gel matrix allowed the PCR cycle number to be reduced to 29 cycles and the D1S80 kit sensitivity to be increased to 2.5 ng from the previous D1S80 Reagent Set specifications of 30 cycles and 5 ng, respectively. PMID- 7782747 TI - Adolescent psychopathy in relation to delinquent behaviors, conduct disorder, and personality disorders. AB - The purpose of this study was to explore the relationship between psychopathy as measured by The Revised Psychopathy Checklist (PCL-R) and delinquent behaviors, conduct disorder, and personality disorders in psychiatrically hospitalized adolescents. Thirty adolescent inpatients were assessed for psychopathy, delinquent behaviors, DSM-III-R Axis I disorders, and personality disorders using the Revised Psychopathy Checklist (PCL-R), the Diagnostic Interview for Children and Adolescents (DICA-R), and the Structured Interview for DSM-III-R Personality Disorders (SIDP-R). Significant relationships were noted between elevated PCL-R psychopathy scores and delinquent behaviors, conduct disorder, and narcissistic personality disorder. The validity of the PCL-R as a measure of psychopathy in adolescence was supported. Longitudinal studies are needed to clarify the clinical application of the PCL-R to adolescent populations. PMID- 7782748 TI - Homicide in psychiatric in-patient facilities: a review, a six-year study, and a case report. AB - Many research studies have attempted to explore the apparent relationship between mental illness and violence. These studies have generally examined the rates of violence during one of three phases: before, after, or during psychiatric hospitalization. Violence that takes place during psychiatric hospitalization has unique implications for both patients, treatment facilities, and for research on violence. This area therefore deserves special study. This article focusses on the most extreme violence that can take place on the wards of a psychiatric facility, assaults resulting in death. This article reviews the literature in this area, reports on a study of the incidence of such occurrences in New York State, and reports in some detail on an additional case which occurred prior to the period under study. The study presented here found that amongst all psychiatric facilities in New York State in six year period there were three cases of in-patient homicide. An average of approximately 90,000 people were served within these facilities during each of the years under study. Suggestions are made for further research in this area. PMID- 7782750 TI - Offender and offense characteristics of sexual sadists: a comparative study. AB - This paper compares the offender and offense characteristics of 30 sexually sadistic criminals studied by Dietz et al. with those of 29 sexually sadistic criminals and 28 nonsadistic sexual offenders from the Royal Ottawa Hospital. We examined whether the characteristics noted by Dietz et al. would be found among a less violent group of sadistic offenders and also to what extent these characteristics were specific to sexual sadism. Results suggest some offender and offense characteristic are specific to sexual sadism and that others appear to be common to sexually aggressive offenders more generally. In addition, there were a number of characteristics found exclusively among the most violent offenders described by Dietz et al. An explanation of these results in terms of a biopsychosocial understanding of sexual sadistic offenders is provided. PMID- 7782749 TI - A psychiatric-legal analysis of psychotic criminal defendants charged with murder. AB - A sample of 25 criminal defendants charged with murder and suffering from psychosis from a large urban multi-ethnic, multi-cultural community pool was studied. Subject characteristics and information about the homicide and decedents are described. Suggestions for further study are briefly discussed. PMID- 7782751 TI - HLA-DQA1 and amelogenin coamplification: a handy tool for identification. AB - A protocol for HLA-DQA1 and gender identification by single amplification is described. The use of the commercial HLA-DQA1 amplification kit (Perkin Elmer) permits a positive response for sex determination by adding primers for a short sequence on the first intron of Amelogenin gene. The suggested amplification protocol results in PCR products easily and clearly detectable on ethidium bromide stained agarose gel or silver stained polyacrylamide gel. In both gels the HLA-DQA1 observations at 242-239 bp are accomplished with a single band at 106 bp in females and a doublet 112-106 bp in males. HLA-DQA1 reverse dot-blot hybridization is unaffected by the presence of X and Y amplified fragments. PMID- 7782753 TI - Viscosity comparisons of polydimethylsiloxane lubricants in latex condom brands via Fourier self-deconvolution of their FT-IR spectra. AB - Many brands of latex condoms use a polydimethylsiloxane lubricant. The lubricant viscosity in ten different brands was compared by determining the average chain length through the ratio of the dimethyl to trimethyl peak area obtained after applying the resolution enhancement technique of Fourier self-deconvolution to their diffuse reflectance FT-IR spectra in the area around 800 cm-1. PMID- 7782752 TI - Restriction fragment length polymorphism (RFLP) typing of DNA extracted from nasal secretions. AB - The restriction fragment length polymorphism (RFLP) analysis of blood, semen, and other body fluids, has become increasingly important in violent criminal cases. The identification of additional tissues suitable for comparison with suspected donors has obvious potential benefit. One type of tissue, that found in nasal secretions, has previously received little attention with regards to genetic analysis. We collected blood and nasal secretion samples from eight individuals, subjected them to traditional RFLP typing methods, and analyzed the results using probes for loci D2S44, D1S7, D10S28, D4S139, and D17S79. All nasal samples provided high DNA yields and hybridization results that matched the corresponding blood standards. Thus, nasal secretions are shown to have potentially significant evidentiary value. PMID- 7782754 TI - A fatality and the American mountain lion: bite mark analysis and profile of the offending lion. AB - Attacks on humans by mountain lions have been infrequent in the history of the United States. Of the 64 authenticated attacks since 1890 in North America, there have been 13 fatalities. This paper reports a case of an adult mountain lion which attacked and killed a female jogger during the spring of 1994 in California. The lion left an imprint of its teeth on the victim's chin. The authors used this bite mark to aid authorities in profiling the approximate age and gender of the attacking animal. The authors subsequently utilized bite mark analysis to establish that the lion actually responsible for the attack had been removed from the area. PMID- 7782755 TI - Sexual asphyxiation: an unusual case involving four male adolescents. AB - A case of sexual asphyxiation is described involving children, adolescent males, homosexuality and two bizarre strangulations. Two adolescent males (ages 13 & 10) initially engaged in homosexual activity in conjunction with sexual asphyxiation. This unusual activity was by chance observed by one of the boy's younger brother and his friend. The younger children (aged 7 & 8) expressed a desire to join in the activity, which they did by letting ligatures be tied around their necks and engaging in anal intercourse to the point of fatal asphyxiation. The case is of interest in the reported way the younger boys discovered the practice (a sexually explicit magazine) and is unusual because of the young ages of the boys involved. PMID- 7782756 TI - Fatal injuries in a minor traffic collision. AB - An elderly woman was the driver and sole occupant of a midsize car involved in a minor collision with a standard sized automobile. She was restrained with a lap and shoulder belt and the air bag was deployed. Yet she suffered fatal chest injuries. No injuries were sustained by the unrestrained driver and passenger of the larger vehicle. Despite maximum restraint in a fully functioning new model car, even a minor collision can be fatal. PMID- 7782757 TI - Hamartomatous malformation of the left ventricle associated with sudden death. AB - We describe unusual left ventricular cardiac lesions in a 17 year old boy who died suddenly during exertion. These consisted of two grossly evident regions of deficient myocardium, containing cavernous spaces which represented exaggerated intertrabecular regions of the left ventricular cavity. Dense fibro-elastotic tissue was deposited around these spaces along with a variable admixture of mature adipose tissue, fibrous tissue and blood vessels. The etiology of these presumably congenital developmental abnormalities is obscure. The lesions most probably represent a hamartomatous malformation, which is a poorly documented pathological entity. PMID- 7782758 TI - Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication. AB - The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication. PMID- 7782759 TI - Detection of drugs-of-abuse in meconium of a stillborn baby and in stool of a deceased 41-day-old infant. AB - When blood or urine is unavailable, postmortem meconium or stool from infants or stillbirths can be used to detect drugs-of-abuse, thus providing datum in assessing drug-abuse exposure. Two case reports illustrate how drugs-of-abuse findings in post-mortem specimens were used to substantiate exposure prior to death or a history of maternal drug abuse. The first, a congenital hydrocephalus, born to a non-drug abusing mother, expired at the age of 41 days, had opiates in the stool by screening method, enzyme multiplied immunoassay technique, confirmed by gas chromatographic/mass spectrometric (GC/MS) analysis. Investigation revealed that morphine had been administered for three days prior to death. The second was a stillbirth infant born to a drug abuser. Almost equal amounts of benzoylecgonine were found in different bowel segments, a finding consistent with admitted cocaine use throughout pregnancy. PMID- 7782760 TI - Differentiation of perimortem and postmortem trauma using taphonomic indicators. AB - Skeletal remains discovered at a construction site in Georgia display classic "butterfly" fractures on several long bones. Although this fracture pattern is usually associated with perimortem trauma, in this case taphonomic indicators demonstrate that they can also occur on dry defleshed bone. Variations in bone color at the fracture sites indicate recent postmortem trauma. Analysis of the directions of force and points of impact indicates that the bones were most likely disarticulated when the trauma occurred. PMID- 7782761 TI - Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge. AB - As part of an in vivo titration study of the macaque simian immunodeficiency virus (SIVmac) strain 251/spl, macaques were inoculated intravenously with various dilutions of this infectious SIVmac. Seven animals received dilutions from 10(-3) to 10(-6) of SIVmac251/spl. Two monkeys infected with the 10(-3) dilution of SIVmac exhibited a productive infection as indicated by seroconversion, detection of genomic RNA and proviral DNA and positive virus isolation. These animals showed a cytotoxic T cell (CTL) response against different SIVmac proteins without any measurable T cell proliferation. The five macaques receiving higher virus dilutions did not seroconvert and were negative for both viral RNA and for infectious virus, although proviral DNA was detected in their peripheral blood mononuclear cells. In contrast to the animals receiving the 10(-3) virus dilution, these five silently infected monkeys developed an SIV specific proliferative T cell response but SIV-specific CTL could not be observed. The SIV-specific T cell proliferation of the silently infected animals could be boosted by a second low-dose exposure with a 10(-4) or 10(-5) dilution of SIVmac251/spl. The virological status of the animals was not changed following this second virus inoculation. Four months later these macaques were challenged intravenously with 2 ml of a 10(-4) dilution of SIVmac251/32H containing 10 monkey ID50. After this challenge all SIV-pre-exposed animals and three naive controls became productively infected. In addition, all infected animals developed typical signs of an immunodeficiency within 6 months after infection. These observations indicate that macaques infected silently by a low-dose exposure to infectious virus generated a virus-specific cellular immune response. However, SIV-specific T cell proliferation alone could not protect the monkeys against an intravenous challenge with SIVmac and the subsequent development of AIDS-like symptoms. PMID- 7782762 TI - Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells. AB - Langerhans cells (LC), the dendritic antigen presenting cells of the skin, mature into potent immunostimulatory cells during migration to regional lymph nodes, where they are identified as interdigitating cells (IDC). Since mature Langerhans cells (mLC) resemble IDC in phenotype and immunostimulatory capacity, we examined whether these cells were susceptible to infection with macrophagetropic and lymphotropic strains of human immunodeficiency virus type 1 (HIV-1). Highly purified cell preparations of mLC migrating from human epidermis expressed high amounts of major histocompatibility complex (MHC) class I and II antigens and of the accessory molecules CD40, CD80 and CD86, indicative of the phenotype of potent immunostimulatory cells. CD4 expression was upregulated on mLC during cultivation, independent of the presence of tumour necrosis factor alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture medium. The macrophagetropic HIV-1 strain SF162 replicated to higher titres in mLC than the lymphotropic strain IIIB. Both strains induced syncytia, with SF162 showing a more rapid cytopathic effect. Addition of TNF-alpha enhanced virus production, due to better cell viability under TNF-alpha treatment, whereas GM-CSF did not significantly influence viability of cells and replication pattern of the virus. These findings suggest that in the infected individual IDC in lymph nodes may function as target cells for HIV-1. PMID- 7782763 TI - Human immunodeficiency virus type 1 infection of human CD4-transgenic rabbits. AB - Investigations of human immunodeficiency virus (HIV) infection of man have benefited from the study of relevant animal models of the infection and disease. However, the ultimate models use primate species which are either endangered, not generally available, or expensive to maintain. A transgenic rabbit specifically and stably expressing human CD4 protein on T lymphocytes was assessed as a new laboratory animal model for HIV-1 infection. In vitro studies demonstrate that lymphocytes derived from the transgenic rabbits are more susceptible to HIV-1IIIB infection than those from normal rabbits. In vivo infection of huCD4-transgenic rabbits using HIV-1IIIB-infected autologous lymphocytes was demonstrated by virus isolation, detection of HIV-1-specific DNA in peripheral blood lymphocytes and seroconversion to various HIV-1 proteins. Viral DNA was detected in the tissues of one rabbit sacrificed 7 weeks post-infection and virus was isolated from lymph node. Although these transgenic rabbits are less sensitive to HIV-1 infection than man, such a small and inexpensive animal model may be a useful tool. PMID- 7782764 TI - Isolation of the causal virus of infectious salmon anaemia (ISA) in a long-term cell line from Atlantic salmon head kidney. AB - A long-term cell line (SHK-1) supporting replication of the causal virus of infectious salmon anaemia (ISA) has been established. The cell line was developed from a culture of Atlantic salmon (Salmo salar L.) head kidney cells. CPE was observed in SHK-1 cells 12-14 days after inoculation with ISA-infective tissue material. The time for CPE to develop decreased after repeated passages of medium from infected cell cultures to new cultures. Transmission trials demonstrated that Atlantic salmon parr developed ISA after intraperitoneal injection of preparations made from infected cells and growth medium. The ISA infectivity of the cell preparations increased with incubation time of inoculated cells. Cell cultures in a second passage were found to have a higher infectivity than the primary inoculated cultures. Virus particles with a diameter of approximately 100 120 nm, and which contained an external envelope and granules were seen in electron micrographs of thin sections of infected cells. Most of the virus particles were located extracellularly close to the cell surface, and in some cases, a connection between virus and plasma membrane could be observed. This indicates that virus particles were released by budding. Enveloped virus particles of 45-140 nm in diameter were seen in abundance in electron micrographs of a negatively stained purified virus preparation. Large, highly pleomorphic particles up to 700 nm in the longest dimension were occasionally observed in unpurified preparations. The evidence is therefore strong that the virus isolated in SHK-1 cells is the aetiological agent of ISA. PMID- 7782765 TI - Production, characterization and reactivity of monoclonal antibodies to porcine reproductive and respiratory syndrome virus. AB - This report describes the preparation of six monoclonal antibodies (MAbs) raised against a British isolate of porcine reproductive and respiratory syndrome virus (PRRSV), their characterization in terms of protein specificity and their reactivity with different PRRS viruses from Europe and the USA. Radioimmunoprecipitation and Western blotting studies of MAb reactivity with proteins from cell lysates of infected cells and purified virus revealed that four of the six MAbs (WBE1 and WBE4-6) precipitated a 15 kDa viral protein. Further studies using in vitro translated products of the Lelystad virus genome showed that this protein was the product of ORF7, the putative nucleocapsid protein. The specificity of another MAb, WBE2, was found to be for a 45 kDa protein, determined to be the product of ORF3 and demonstrated to be present in purified virion preparations. The protein specificity of the sixth MAb, WBE3 could not be determined. Thirty-three PRRSV isolates from Europe and the USA were grown in alveolar macrophages and examined by immunoperoxidase staining, using the panel of six MAbs. All European isolates were recognized by the four MAbs specific for the putative nucleocapsid, but the viruses showed different patterns of reactivity with WBE2 and WBE3. Furthermore, these two MAbs stained only a small proportion of the cells infected with certain isolates, suggesting that a single isolate may be antigenically heterogeneous. No MAbs bound to US isolates, indicating a consistent antigenic difference between the putative nucleocapsid of US and European isolates. Detergent extraction of cell lysate antigen abrogated the binding of WBE1-3, suggesting that the epitopes are conformation dependent. PMID- 7782766 TI - Cholera toxin B stimulates systemic neutralizing antibodies after intranasal co immunization with measles virus. AB - An efficient mucosal vaccination has a number of obvious advantages over invasive routes of immunization. The immune response to measles virus (MV) was investigated after intranasal and intragastric co-immunization of mice with cholera toxin B (CTB) as an adjuvant. High titres of virus-specific IgG antibodies and a transient IgA response were detected in the sera after intranasal but not after intragastric immunization when CTB was used. In the presence of CTB, higher titres were reached with less antigen and fewer intranasal boosts. Neutralizing antibodies were found in all animals only after co-immunization with MV and CTB. In the nasal wash and the saliva, IgG and IgA titres were significant only in the MV plus CTB groups; IgG levels were comparable to those found after intraperitoneal (i.p.) immunization with complete Freund's adjuvant. Specific IgA was detected in the mucosal fluids only after intranasal immunization with MV plus CTB but not after i.p. or intragastric immunization. The antibody response consisted of 99% IgG1 after MV immunization. In the CTB groups 10% IgG2b and 1% IgG2a were detected in addition to the predominant IgG1 antibodies. PMID- 7782767 TI - The Epstein-Barr virus open reading frame BDLF3 codes for a 100-150 kDa glycoprotein. AB - The Epstein-Barr virus (EBV) open reading frame BDLF3 is predicted to code for a glycoprotein on the basis that it contains sequences with signal peptide and transdomain characteristics and nine potential N-linked glycosylation sites. No sequential or positional homologues of BDLF3 have been located in other herpesviruses. A bacterial glutathione S-transferase (GST)-BDLF3 fusion protein was used to demonstrate that over one-third of EBV-immune human sera tested recognized the fusion protein but not GST alone on Western blots. The fusion protein was used to raise polyclonal sera in rabbits. A BDLF3 recombinant baculovirus was constructed using the full-length BDLF3 sequence (AcBDLF3). Rabbit anti-fusion protein sera and some human EBV-immune sera recognized products of approximately 30 and 55 kDa from AcBDLF3-infected insect cells by Western blotting. A peptide representing the carboxy-terminal amino acids 215-234 of the BDLF3 sequence was used to raise anti-peptide sera in rabbits. Anti peptide serum detected a product by indirect immunofluorescence in acetone-fixed EBV-infected B cells from all cell lines tested. A diffuse band with a molecular mass of 100-150 kDa was detected by Western blot in B95-8 cell lysates, partially purified B95-8 virus and B95-8-infected cell membranes after probing with anti BDLF3 peptide serum. This product was shown to be glycosylated after enzymatic deglycosylation of a B95-8 virus preparation using neuraminidase, O-glycosidase or N-glycosidase F. The BDLF3 protein products have no known function. PMID- 7782769 TI - Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication. AB - Valproic acid (VPA), a simple branched-chain fatty acid having anticonvulsant activity and used in the treatment of many forms of epilepsy, markedly stimulated human cytomegalovirus (HCMV) replication in human fibroblasts (MRC-5 cells). The maximum level of stimulation was reached when cells were treated for 24 h before infection. The enhancement of virus replication correlated with an increase in the number of immediate early (IE) and early (E) antigen-positive cells. VPA also induced expression of IE antigens after transfection of fibroblasts with a plasmid containing the entire IE1-2 region. Moreover, VPA stimulated the HCMV IE1 2 promoter/enhancer-mediated expression of beta-galactosidase in a stably transfected Jurkat T cell line. Recently, VPA was shown to inhibit glutathione reductase in human red blood cells, but an action through the glutathione metabolic pathway can be eliminated in this case, since VPA decreased the intracellular level of glutathione in Jurkat T cells but not in MRC-5 cells. The ability of VPA to stimulate HCMV replication provides an attractive model for studying the molecular mechanism of the regulation of HCMV IE1-2 gene expression. PMID- 7782768 TI - Qualitative analysis of the expression of Epstein-Barr virus lytic genes in nasopharyngeal carcinoma biopsies. AB - We recently showed that BZLF1, the gene encoding the Epstein-Barr virus (EBV) ZEBRA protein, was expressed in all eight nasopharyngeal carcinoma (NPC) specimens studied. We present here studies on the expression of EBV lytic cycle genes in the same eight NPC biopsies to determine if production of the ZEBRA transactivator could lead to a complete productive cycle. The tumour lesions exhibit a number of different patterns of limited lytic gene expression. In three out of eight tumours neither BRLF1 nor BMLF1 expression could be detected. Otherwise BMLF1 mRNA was expressed in all the other specimens. Three specimens also expressed BRLF1. Two specimens not only exhibited BZLF1, BMLF1 and BRLF1 transcripts, but also expressed the late gene BLLF1 which encodes the membrane protein gp220. The early gene product BBLF2 could not be detected in any of the eight NPC. However, expression of the late gene encoding the lytic truncated form of LMP1 (D1LMP) was found in seven of the eight NPC biopsies. Thus, it could be suggested that the EBV abortive lytic cycle occurred in most of the NPC studied. PMID- 7782770 TI - Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. AB - The development and utilization of a tissue culture system for the analysis of quiescent, nonreplicating herpes simplex virus type 1 (HSV-1) genomes is described. It was demonstrated previously that the HSV-1 Vmw65 mutant in1814, which is impaired for immediate early (IE) transcription, was retained for many days in human fetal lung (HFL) fibroblasts in a quiescent 'latent' state. Molecular analysis of the viral genome was not possible, however, due to residual expression of IE proteins and consequent cytotoxicity at high m.o.i. In the study reported here, IE transcription was reduced further by pretreatment of cells with interferon-alpha (IFN-alpha) and by the use of mutant in1820, a derivative of in1814 in which the Vmw110 promoter was replaced by the Moloney murine leukaemia virus (Momulv) enhancer. The Momulv enhancer was not expressed under IE conditions; thus in1820 was more impaired for replication than in1814 and behaved as if deficient for both Vmw65 and Vmw110. In cells pretreated with IFN-alpha and subsequently infected with in1820 cytotoxicity was overcome, enabling a tissue culture system to be developed in which all cells stably retained at least one quiescent viral genome. To assist the analysis of gene expression, in1820 was further modified by insertion of the Escherichia coli lacZ gene controlled by the human cytomegalovirus enhancer (mutant in1883) or the HSV-1 immediate early Vmw110 promoter (in1884). Expression of beta-galactosidase was not detected after infection of IFN-alpha-pretreated cells with in1883 or in1884 but could be induced in almost all cells containing a viral genome, by superinfection of cultures. In1820-derived viruses were retained for at least 9 days and were not reactivated by subculture of cells. A regular arrangement of nucleosomes, as found in cellular chromatin, was not detected on the viral genome at the thymidine kinase locus. The non-linear genome was a template for reactivation with no requirement for prior conversion to a linear form. A small number of remaining linear genomes resulted from incomplete uncoating of input virus. PMID- 7782771 TI - Role of viral proteins and concanavalin A in in vitro replication of pseudorabies virus in porcine peripheral blood mononuclear cells. AB - We examined the capability of pseudorabies virus (PRV) to replicate in vitro in porcine peripheral blood mononuclear cells (PBMC) and characterized the phenotype of infected cells. In addition, we investigated whether inactivation of various PRV proteins or the expression of a foreign gene affected this replication. Finally, we studied the replication of PRV strains in concanavalin A (Con A) stimulated lymphocytes. The replication of PRV mutants with inactivated glycoproteins gE or gG, thymidine kinase (TK), ribonucleotide reductase (RR) or US3-encoded protein kinase (PK), and the replication of PRV vector strains expressing the envelope glycoprotein E1 of hog cholera virus (HCV) were studied. By adherence of PBMC to plastic, monocytes and lymphocytes were largely separated. Infected monocytes were analysed with an immunostaining monolayer assay and infected lymphocytes were analysed with immunofluorescence staining and flow cytometry. We found that the wild-type NIA-3 virus replicated in both lymphocyte and monocyte cultures. NIA-3 infected relatively more monocytes (> 90%) than non-adherent B cells (46-65%) and T cells (17-28%); approximately equal numbers of CD4+ and CD8+ T cells were infected. Although E1 is probably involved in adsorption of HCV to host cells, the expression of E1 by PRV vector strains did not change the level of replication. Inactivation of TK and RR, but not inactivation of gE, gG or PK, severely affected the replication in both monocytes and lymphocytes. Con A stimulation of lymphocytes restored the reduced replication of the TK mutant, but not of the RR mutant. Moreover, Con A stimulation of lymphocytes reduced the replication of the wild-type NIA-3 virus. We concluded that both viral TK and RR activity are important for efficient replication of PRV in resting lymphocytes. Furthermore, Con A-stimulated lymphocytes can restore the viral TK defect and PRV replication can also be influenced by cellular metabolism. PMID- 7782772 TI - Nucleotide sequence and transcriptional analysis of the gp41 gene of Spodoptera frugiperda nuclear polyhedrosis virus. AB - The Spodoptera frugiperda multiple nucleocapsid nuclear polyhedrosis virus (SfMNPV) gp41 structural protein gene was located in the 1.9 kbp EcoRI-S fragment and sequenced. An open reading frame (ORF) of 999 nucleotides was detected that encoded a protein of 332 amino acids. The gp41 gene transcript was detected after 12 h post-infection (p.i.) and remained detectable at 48 h p.i. Two major mRNAs, about 1.6 and 2.8 kb in length, were determined by Northern blot analysis. Primer extension analysis demonstrated that the gp41 gene promoter region contains three transcription start sites. Two of the gp41 gene transcription start sites were located at -42 and -41 nucleotides from the ATG translation start codon within a consensus late transcription start site (TAAG) and another transcription start site was located at -140 nucleotides from the ATG translation start codon for which no consensus motif has been determined. Comparison of SfMNPV gp41 nucleotide and amino acid sequences with the gp41 genes from Autographa californica, Bombyx mori, and Helicoverpa zea NPVs showed 60% homology of nucleotide sequences and 70% similarity of amino acid sequences. PMID- 7782773 TI - Mutations in the Autographa californica multinucleocapsid nuclear polyhedrosis virus 25 kDa protein gene result in reduced virion occlusion, altered intranuclear envelopment and enhanced virus production. AB - Serial passage of nuclear polyhedrosis viruses (NPVs) through cultured cell lines results in the appearance of mutants with a complex phenotype referred to as the 'few polyhedra' (FP) phenotype. The altered plaque morphology and reduced occlusion production associated with the FP phenotype have been observed in Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) bearing mutations in the gene encoding the 25 kDa protein (25K gene). In this study, we sequenced the 25K genes of four spontaneously occurring AcMNPV FP mutants. These mutants, together with an artificially generated FP mutant (AcFP beta gal, in which the gene for beta-galactosidase is fused in frame with the 25K ORF), were examined at the ultrastructural level to see if they exhibited the reduced virion occlusion and intranuclear envelopment which is associated with the FP phenotype. Observations on Spodoptera frugiperda Sf9 cells infected with the FP mutants revealed that all five mutants were impaired in virion occlusion and intranuclear nucleocapsid envelopment. The 25K mutants were also found to release two- to fivefold more infectious virus (p.f.u.) into the media of infected Sf9 cells. Marker rescue of AcFP beta gal restored wild-type virion occlusion, intranuclear envelopment and levels of infectious virus production. PMID- 7782774 TI - Genome organization of a partitivirus from the filamentous ascomycete Atkinsonella hypoxylon. AB - We have identified viruses in several isolates of the filamentous ascomycete Atkinsonella hypoxylon. The virus from one isolate of the fungus, 2H, was selected for genomic characterization. Purified virus particles contained three dsRNAs with sizes estimated by gel electrophoresis to be 2.2, 2.1 and 1.8 kb. A library of cDNA clones representing the three dsRNA segments of isolate 2H was synthesized, mapped and sequenced. The three segments had no significant similarity to each other, as determined by Northern blot analysis, and had sizes of 2180, 2135 and 1790 nt as determined by nucleotide sequence analysis. Long open reading frames were deduced from the sequences of dsRNAs 1 (molecular mass 78 kDa) and 2 (74 kDa), but not from dsRNA 3. Both terminal regions of dsRNA 1 and dsRNA had similar nucleotide sequences, as determined from 5' RACE clones. Comparisons of the amino acid sequence deduced from dsRNA 1 revealed similarities with viral RNA-dependent RNA polymerases. Translation in vitro of full-length cDNA clones representing dsRNAs 1 and 2 each yielded single major products of > 70 kDa by analysis on polyacrylamide gels. Based on properties of its dsRNA segments, the virus of A. hypoxylon strain 2H fits into the Partitiviridae family, and represents the first member of this family from a fungal host completely characterized at the level of primary nucleotide sequence. PMID- 7782775 TI - The genome organization of banana bunchy top virus: analysis of six ssDNA components. AB - We have cloned, sequenced and analysed an additional five circular ssDNA components of banana bunchy top virus (BBTV) which we have called components 2, 3, 4, 5 and 6. These components were present in all BBTV infections tested. Four of these components (components 3, 4, 5 and 6) had one large open reading frame (ORF) in the virion sense located 3' of a stem-loop structure. Each ORF had a potential TATA box and one or two potential polyadenylation signals associated with it and each polyadenylation signal had an associated GC-rich region containing the trinucleotide sequence TTG. A number of ORFs were identified in component 2 but none of these had appropriately located potential TATA boxes and polyadenylation signals associated with them. None of the ORF amino acid sequences nor the full DNA sequences of any of the components had significant sequence identity with any known protein or nucleic acid sequences. However, the ORF of component 4 encoded a 30 residue hydrophobic domain which may indicate that this ORF encoded a transmembrane protein. Further, the ORFs of components 3 and 5 potentially encoded proteins of about 20 kDa, the size of the BBTV coat protein. There were two regions of sequence identity between the five components described here and the previously described component 1. Each component contained a conserved stem-loop structure and a nonanucleotide potential TATA box which was 5' of the large virion-sense ORF in five of the components. The stem-loop structures were incorporated in a common region (CR-SL) of 69 nucleotides which was 62% identical between components. All six BBTV components also contained a major common region (CR-M) which was located 5' of the CR-SL in each component, in the non-coding region and was 76% identical over 92 nucleotides. Each CR-M contained a near-complete 16 nucleotide direct repeat and a GC-box which was similar to the rightward promoter element found in wheat dwarf geminivirus. From these results, BBTV appears to belong to an undescribed plant virus group which could also include subterranean clover stunt virus, coconut foliar decay virus, faba bean necrotic yellows virus and milk vetch dwarf virus. PMID- 7782776 TI - Isolation and characterization of an RNA-dependent RNA polymerase from Nicotiana clevelandii plants infected with red clover necrotic mosaic dianthovirus. AB - A template-bound RNA polymerase was isolated from Nicotiana clevelandii plants infected with red clover necrotic mosaic dianthovirus (RCNMV) by differential centrifugation, solubilization with dodecyl beta-D-maltopyranoside, and chromatography on columns of Sephacryl S-400 and Q-Sepharose. Analysis of the purified polymerase by SDS-polyacrylamide gel electrophoresis, followed by silver staining or immunoblotting, showed that it contained virus-encoded proteins of molecular masses 27 kDa and 88 kDa together with several minor proteins possibly of host origin. After removal of endogenous RNA with micrococcal nuclease, the polymerase became template-dependent. It was also template-specific, being able to utilize as templates RNA of two strains of RCNMV, but not RNAs of three viruses in different taxonomic groups, namely cucumber mosaic cucumovirus, tomato bushy stunt tombusvirus and tomato mosaic tobamovirus. The products of RNA polymerase reactions were double-stranded RNAs corresponding to RCNMV RNAs 1 and 2. The ability of the template-dependent RNA polymerase to synthesize RNA was completely inhibited by antibodies to a peptide containing the GDD motif, whereas the activity of the template-bound enzyme was unaffected by these antibodies. PMID- 7782778 TI - Antigenic analysis of nematode-transmissible and non-transmissible isolates of tobacco rattle tobravirus using monoclonal antibodies. AB - Murine monoclonal antibodies (MAbs) were produced against a nematode non transmissible isolate of tobacco rattle tobravirus (TRV-PLB). Two of the MAbs (SCR 80 and 81) did not react with the serologically closely related isolate TRV PPK20 (both isolates belong to the PRN serotype), which is readily transmissible by nematodes. When further isolates of the PRN serotype were tested, all the non transmissible ones reacted with these two MAbs, but so also did some of those that are readily transmissible. SCR 80 and 81 were able to trap TRV-PLB particles onto electron microscope grids and reacted with metatopes located near the C terminus of the particle protein. The epitope recognized by SCR 81 was discontinuous. The MAbs that reacted with both TRV-PLB and TRV-PPK20 recognized either continuous cryptotopes (SCR 78) or discontinuous neotopes (SCR 79 and 82). PMID- 7782779 TI - Expression, subcellular location and modification of the 50 kDa protein encoded by ORF2 of the apple chlorotic leaf spot trichovirus genome. AB - A putative movement protein of molecular mass 50 kDa encoded by the ORF2 of the apple chlorotic leaf spot virus (ACLSV) genome was expressed in Escherichia coli using an expression vector and was then used to produce an antiserum. Immunoblot analysis using an antiserum raised against this protein showed that the ORF2 protein of ACLSV was detected in both cell wall and cell membrane fractions prepared from infected Chenopodium quinoa tissues. The ORF2 protein from infected tissues had a molecular mass of 52 kDa, larger than that of the full-length ORF2 protein (50 kDa protein) expressed in E. coli. Incubation of the 52 kDa protein with alkaline phosphatase resulted in a decrease in its apparent molecular mass from 52 kDa to 50 kDa, strongly suggesting that the ORF2 protein of ACLSV is phosphorylated in infected plant tissues. PMID- 7782777 TI - The tobacco necrosis virus p7a protein is a nucleic acid-binding protein. AB - The two centrally located open reading frames (ORFs) of necroviruses may, by analogy with the similarly located and related ORFs of carmoviruses, be expected to have a function in virus movement in plants. In the case of tobacco necrosis virus (TNV) strain D these proteins both have a molecular mass of approximately 7 kDa and are thus known as p7a and p7b. We overexpressed p7a in Escherichia coli, separated it from bacterial proteins and renatured it on gels, and showed that p7a was able to bind single-stranded RNA and single-stranded DNA, but was unable to bind double-stranded DNA. These protein-nucleic acid complexes were stable at moderately high salt concentrations. Protein p7b could not be expressed in a number of bacterial systems. We speculate that in TNV, unlike some other viruses which encode a single movement protein with separate functional domains for RNA binding and plasmodesmatal targeting, p7a and p7b may respectively provide these functions on separate proteins. PMID- 7782780 TI - The glycosylation of human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) is important for the efficient intracellular transport of the envelope precursor gp160. AB - The role of the glycans of the human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) in the intracellular events of Env precursor (gp160) biosynthesis has been examined by the use of a mutant gp160 in which the cluster of conserved glycosylation sites within the gp41 domain (Asn-621, -630 and -642) has been mutated. Expression of the wild-type and mutant forms of gp160 in BHK-21 cells using recombinant vaccinia viruses has shown that the kinetics of the events occurring in the endoplasmic reticulum (ER) were normal: both Env proteins had similar kinetics of disulphide bond formation, as determined by the acquisition of CD4-binding capability, and both had similar kinetics of oligomer formation. However, in contrast to the parental molecule, mutated gp160 displayed relatively slow transport from the cis to the medial Golgi where it was retained in the oligomeric state. Transport to the trans Golgi was impaired, as determined by the sensitivity of gp160 to glycosidases. Cleavage of mutated gp160 at the gp120/gp41 junction was substantially reduced but this was apparently not due to the involvement of the gp41 glycosylation in the cleavage reaction by furin inasmuch as, in the baculovirus system, mutated gp160 could be cleaved when recombinant furin was co-expressed. The reduced cleavage in mammalian cells may thus reflect the impaired routing of mutated Env to the compartment where cleavage occurs. The glycan component of gp41 is, therefore, important for the efficient intracellular transport and processing of gp160. gp160 lacking gp41 carbohydrates is an additional example, among few others, of a protein lacking glycans that is arrested in the Golgi rather than the ER following its biosynthesis. PMID- 7782782 TI - Genetic stability of cold-adapted A/Leningrad/134/47/57 (H2N2) influenza virus: sequence analysis of live cold-adapted reassortant vaccine strains before and after replication in children. AB - We previously reported that the A/Leningrad/134/47/57 (H2N2) cold-adapted virus (A/Len/47) used in preparing reassortant live attenuated vaccines for children acquired 14 (11 coding) mutations in genes coding for proteins other than haemagglutinin and neuraminidase during cold-adaptation. Preservation of these mutations in genomes of viruses isolated from children on the second, fifth, or eighth day after vaccination was examined by sequence analysis. The sequence data demonstrated that all nine coding mutations selected for examination were conserved in the genomes of all 11 strains investigated, indicating that the mutations accompanying cold-adaptation and attenuation of the A/Len/47 master vaccine are highly stable. PMID- 7782783 TI - Expression of beta-galactosidase in neurons of dorsal root ganglia which are latently infected with herpes simplex virus type 1. AB - Explanation into culture of dorsal root ganglia (DRG) latently infected with herpes simplex virus type 1 (HSV-1) causes reactivation of the virus. Previous studies have suggested that either latency-associated transcripts (LATs) were removed as an early consequence of reactivation or, alternatively, there was a population of latently infected cells which did not contain LATs. We have now attempted to detect this population of neurons by inserting a reporter gene (Escherichia coli lacZ gene), under the control of promoters other than LAT, into the HSV-1 strain 17 mutant in 1814, which was used in the earlier studies. One of these promoters, the human cytomegalovirus enhancer, resulted in weak expression of beta-galactosidase in DRG neurons for at least 5 months. The pattern of staining was predominantly homogeneous in neurons at 3 or 5 days post-infection or at 3 days post-explanation, and was predominantly speckled in latently infected neurons (1 to 5 months post-infection). About 30% of the beta galactosidase-positive neurons did not contain LATs by in situ hybridization. However, the detergents used to enable penetration of the substrate for beta galactosidase had also reduced the levels of the LATs; in neurons which originally had only small numbers of LATs this may have reduced levels to below those detectable by the methods used. There was, therefore, no unequivocal evidence for a population of latently HSV-1-infected cells which did not express LATs. PMID- 7782781 TI - Cloning, sequencing and expression of the S1 gene of avian reovirus. AB - The S1 genome segment of avian reovirus strain S1133 was cloned and completely sequenced. The sequence comprised 1636 bp with three distinct open reading frames (ORFs), suggesting the gene was polycistronic in nature. The three ORFs from 5' to 3' were predicted to encode polypeptides of 9.8, 3.8 and 34.9 kDa, respectively. Of the three ORFs, only the third possessed the AUG initiation codon in an optimum context for translation. The third ORF-encoded protein, 326 amino acids in length, was expressed in Escherichia coli and used as antigen in immunoblots. The protein was concluded to be sigma 3 on the basis of its recognition by a chicken anti-reovirus antiserum and due to the fact that a mouse antiserum raised against it recognized specifically the viral sigma 3 polypeptide. Sequence comparison of the avian reovirus S1 gene with its mammalian counterpart did not show any significant similarity between the two. However, amino acid sequence analysis and the predicted existence of a heptapeptide repeat pattern, as well as the relatively high frequency of alpha-helix structures in the amino terminal portion of sigma 3 suggests that this protein is structurally, and probably functionally, related to mammalian reovirus sigma 1 protein. PMID- 7782784 TI - Genomic heterogeneity in the pol region of ovine lentiviruses obtained from bronchoalveolar cells of infected sheep from France. AB - In order to determine the genomic heterogeneity of ovine lentiviruses, we analysed eight isolates from naturally infected sheep from one geographical region of France. A 475 nt fragment in the region of the pol gene coding for reverse transcriptase was amplified by RT-PCR from RNA directly extracted from uncultured bronchoalveolar lavage cells. The resulting PCR fragments were analysed by restriction enzyme digestion, cloned in a TA vector and sequenced. Restriction enzyme analysis showed distinct patterns from the eight isolates, and sequencing showed them to be closely related in both nucleotide (2.3-8.1% variation) and deduced amino acid (0-6.2% variation) sequences. Their amino acid sequences differed from that of visna-maedi virus complete viral genome sequence K1514 by 12.5-15.3%, but from that of caprine arthritis encephalitis virus (CAEV) viral genome sequence Co by only 4.2-6.9%. Phylogenetic analysis showed that the French isolates form a group related to CAEV Co and distant from previously reported ovine lentivirus sequences from different origins. PMID- 7782785 TI - Sequences of VP6 genes of human rotavirus strain RV3 and its vaccine derivative. PMID- 7782786 TI - 2,6-diacetylpyridine bis(thiosemicarbazones) zinc complexes: synthesis, structure, and biological activity. AB - The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds- [Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal -bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds. PMID- 7782788 TI - Novel kinetics in a biomimetic redox reaction involving NADH and tetrazolium salts in aqueous micellar solutions. AB - Aqueous micelles of Triton X-100 are shown to catalyze the redox reaction between NADH and 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazolum chloride (INT) at neutral pH. The reaction exhibits a first-order dependence on NADH when INT is saturating; conversely, when NADH is saturating, the dependence is strictly second-order with respect to INT. The second-order dependence of the reaction on INT is also evident in situations where micelles of a cationic detergent are used in place of Triton X-100. The available kinetic evidence indicates the transient formation of a central complex involving the addition of two molecules of INT and one molecule of NADH to a "site" on the micelle where they are held together until completion of the redox process. However, the reaction does not seem to proceed by successive 1-e- steps, suggesting that the second-order dependence on INT has no bearing on the mechanism of redox process. The transfer of reducing equivalents between NADH and INT is shown to be direct and quantitative, with the redox steps confined to a microenvironment, as in the case of enzymatic NAD(P)H dependent reactions. A mechanism consistent with the hydridic nature of the migrating hydrogen from the C(4) position of the dihydropyridine nucleus of NADH is proposed, assuming that only one molecule of INT in the central complex participates in the actual redox process and that the other molecule of INT acts as a cocatalyst by way of providing the necessary "basicity" at the reaction site. PMID- 7782787 TI - Effects of thiourea and ammonium bicarbonate on the formation and stability of bifunctional cisplatin-DNA adducts: consequences for the accurate quantification of adducts in (cellular) DNA. AB - Cisplatin reacts with DNA by forming mainly bifunctional adducts via reactive monofunctional intermediates. When freshly platinated DNA was postincubated with thiourea (10 mM, at 23 or 37 degrees C) for periods of up to 24 h, followed by determination of mono- and diadducts, a rapid initial decrease was seen in the fraction of diadducts, followed by a much slower decrease. About 40% diadducts were found after 10-min postincubation at 23 degrees C, which dropped to some 14% after 24 h at 37 degrees C; total platination was hardly affected. Postincubation of "aged" platinated DNA (no reactive monoadducts) only showed the slower decrease. The rapid process is likely to represent monoadduct inactivation, preventing the formation of diadducts, whereas the slow reaction must be interpreted as diadduct-to-monoadduct conversion. Similar reactions, but less efficient than with thiourea, occurred during dialysis against NH4HCO3 (0.1-1 M). Pt-containing (di)nucleotides in digested DNA were hardly affected by thiourea. Rapid reduction of the measured level of bifunctional adducts also occurred when cisplatin-treated Chinese hamster ovary cells were postincubated with thiourea, with concomitant increase in survival. It is concluded that quantification of the real levels of mono- and diadducts in freshly platinated DNA requires a posttreatment with thiourea of 30-60 min at 37 degrees C. PMID- 7782789 TI - An X-ray absorption spectroscopy study of the interactions of Ni2+ with yeast enolase. AB - An x-ray absorption spectroscopy (XAS) study was carried out at pH 7.6 on solutions of Ni2+ and yeast enolase depleted of its physiological cofactor (Mg2+) in the presence or absence of substrate/product, the very strongly bound competitive inhibitor 2-phosphonoacetohydroxamate and Mg2+. Both "conformational" and "catalytic" Ni2+ are distorted octahedral in coordination, in agreement with several spectroscopic studies but in contrast to the coordination in the crystal at pH 6.0. The data are consistent with direct coordination of what must be the catalytic Ni2+ to the phosphate of the substrate, in agreement with some previous data but in disagreement with recent interpretations by other workers. The ligands around the metal ions obtained from the x-ray structure give simulated XAS spectra in good agreement with the observed spectra. PMID- 7782790 TI - Antioxidant effect of inorganic ions on UVC and UVB induced lipid peroxidation. AB - Phosphate buffer suspensions of unilamellar liposomes of phosphatidylcholine were irradiated with UVC (254 nm) and UVB (300 nm) light. The irradiation provoked lipid peroxidation and liposome lysis with release of entrapped glucose-6 phosphate. At the same intensity of absorbed light, the photochemical effect at 254 nm is higher than at 300 nm. The addition of copper(II) and manganese(II) reduced both the peroxidation and the lysis. The copper showed an inhibitory effect only on the process provoked by the 254 nm irradiation, whereas the manganese was efficient both at 254 and 300 nm. The results are interpreted with a mechanism of peroxidation and quenching, involving photoformation of peroxyl radicals that are scavenged by manganese(II) and copper(I), with consequent breaking of the radical chain and reduction of the peroxidation rate. The copper(I), which is the active species, can be formed only at 254 nm by electron capture. The experimental data fit the kinetic equations obtained by the proposed mechanism by means of computer software. PMID- 7782791 TI - Metal ion binding to apo, holo, and reconstituted horse spleen ferritin. AB - The binding of Cd2+, Zn2+, Cu2+, Ni2+, Co2+, Mn2+, and Mg2+ to apo, holo, reconstituted horse spleen ferritin (HoSF), and native holo HoSF with phosphate removed was measured by gel-exclusion chromatography. Three classes of strong binding interactions (Kd < 10(-7) M) with apo HoSF at pH 7.5 were found for the various M2+ studied: high stoichiometric binding (30-54 M2+/HoSF) for Cd2+, Zn2+, Cu2+, with two protons released per metal bound; intermediate binding (16 M2+/HoSF) for Ni2+ and Co2+, with one proton released per metal bound; and low levels of binding (2-12 M2+/HoSF) for Mn2+, Mg2+, and Fe2+, with < 0.5 protons released per metal bound. M2+ binding to apo HoSF was nearly abolished at pH 5.5, except for Fe2+ and Cu2+, which remained unaffected by pH alteration. Holo HoSF bound much higher levels of M2+, a result directly attributable to the presence of phosphate binding sites. This conclusion was confirmed by decreased binding of M2+ to HoSF reconstituted in the absence of phosphate and by native holo HoSF with phosphate chemically removed. The binding of Cd2+ to apo HoSF was 54 per HoSF, but in the presence of developing core, the amount bound decreased to about 30 Cd2+/HoSF. This result indicated that Cd2+ and developing core were competing for the same sites on the HoSF interior, suggesting that 24 of the Cd2+ were bound to the inside surface. No other M2+ studied bound to the interior of HoSF by this criterion. Several of the M2+ appeared to bind strongly to the phosphate free mineral core surface in reconstituted HoSF. PMID- 7782792 TI - Tb3+ binding to human erythrocyte spectrin resulting in conformation change and aggregation. AB - The Tb3+ binding to spectrin tetramer (SPT) was studied by Tb3+ fluorescence titration and CD spectra. The results indicated that the total high-affinity Tb3+ binding sites are n1 = 330, with average Kd = 3.6 x 10(-6) M. Among them, ca. 90 sites are of higher affinity and are probably more specific to Tb3+ than the remaining sites. There are 520 low affinity Tb3+ binding sites with average Kd = 1.5 x 10(-5) M. Fluorescence and CD spectra revealed that the alpha-helix content of SPT decreased with Tb3+ binding to specific sites and further binding did not result in conformation change. Tb3+ binding to SPT and the subsequent reactions were studied by employing stopped-flow fluorescence and light scattering methods. The studies demonstrate that this is a multistep reaction assembly: high-affinity terbium binding-conformation change-aggregation-low-affinity terbium binding--the second conformation change. The critical Tb3+ concentration-induced spectrin dimer (SPD) aggregation was determined with a light scattering method. PMID- 7782793 TI - A semiquantitative food frequency questionnaire for use in epidemiologic research among the elderly: validation by comparison with dietary history. AB - A self-administered semiquantitative food frequency questionnaire including 75 food items and providing information on the habitual intake of 31 nutritional parameters, based on the intake of protein, fat, carbohydrate, fiber and 11 vitamins and minerals, was developed for use in epidemiologic research on chronic disease among the elderly, such as diabetes and cardiovascular disease. By means of detailed frequency and quantity questions, specifications of types of food, preparation methods and seasonal variation, the questionnaire was expected to be an improvement on existing instruments. The relative validity of the questionnaire was examined in 74 men and women, aged 50-75, by comparison with a modified dietary history. Systematic differences were absent or negligible for all nutrients, except vitamin C. Bias depending on the level of intake could be ruled out for all but seven nutrients. Pearson correlation coefficients for estimates from the questionnaire and dietary history were on average 0.71 (range: 0.65-0.78) and 0.66 (range: 0.36-0.81) for macronutrients, and vitamins and minerals, respectively. Classifying individual intake estimates into tertiles of the distribution for both methods, on average 62.4 and 54.7% of the intakes were categorized into the same tertile and 3.9 and 5.9% into the opposite tertile for macronutrients, vitamins and minerals, respectively. These results demonstrate an acceptable relative validity for this newly developed questionnaire, as compared to the dietary history method. PMID- 7782794 TI - Efforts to improve interobserver agreement in histopathological grading. AB - The present study aimed to assess the interobserver variation in histopathological grading of 88 slides by four experienced pathologists who, before the start of the study, reached consensus about the method of grading through a joint session behind a discussion microscope. The results were compared with two previous studies, the first assessing the observer variation under normal conditions, the second doing the same after theoretical agreement about which morphological characteristics were relevant for grading. In the present study the pathologists first made a provisional diagnosis on low power view, followed by a final diagnosis on high power view, scoring various morphological characteristics as in the second study. The unweighted and weighted group kappa values for the final diagnosis were 0.41 and 0.71 respectively in the present study (after the consensus meeting), compared to 0.33 and 0.70 respectively in the second study (after only theoretical consensus), and 0.28 and 0.55 in the first study (without consensus). We conclude that a consensus meeting appears to be useful to improve the interobserver agreement. PMID- 7782795 TI - Medicine, practice and guidelines: the uneasy juncture of science and art. AB - While physicians are often portrayed as scientists, the defining character of medical practice is its being both science and art. Indeed, despite drawing on the ever-expanding knowledge base and range of therapies, medical practice remains fundamentally an interpersonal experience, drawing on the dynamic and rich interaction between practitioner and patient. With the goal of situating clinical practice guidelines in a broader context, we briefly explore models of medicine and the nature of clinical practice. The implications of these for guideline development and implementation are then examined as we present guidelines as an opportunity for enhancing medical practice and increasing both patient and practitioner satisfaction. PMID- 7782796 TI - Fractures and low axial bone density in perimenopausal women. AB - The relationship between past fractures and current bone density (BMD) was analyzed in a population sample of 3222 women aged 48-58. BMD was determined with dual X-ray absorptiometry (DXA) at the spine and femoral neck. 702 women reported fractures. Wrist and ankle were the most common fracture sites. Fracture history increased the risk [OR (95% CI)] of low spinal BMD (of more than 1 SD below the study population mean) by 1.75 (1.41; 2.18). The sensitivity and specificity of fracture history to detect a low spinal BMD were 31 and 80%, respectively. One SD decreases of spinal and femoral BMD equalled to respective overall fracture risks (adjusted ORs) of 1.36 (1.24; 1.50) and 1.38 (1.25; 1.51). Both BMDs related more strongly to wrist fracture [1.73 (1.47; 2.05)/1.69 (1.43; 1.99)] than to all nonwrist fractures combined [1.24 (1.11; 1.37)/1.27 (1.14; 1.42)]. Ankle and rib fractures related only to spinal [1.21 (1.00; 1.46)/1.45 (1.12; 1.87)] but tibia and foot bone fractures only to femoral [2.04 (1.37; 3.04)/2.20 (1.42; 3.41)] BMD. Spinal BMD related more strongly to fractures due to falls on same level than to fractures due to all other trauma combined. Fracture history poorly screens out low perimenopausal BMD. The results suggest that pre- and perimenopausal fractures relate to low axial bone density and that the magnitude of this relation depends on the sites of fracture and densitometry as well as on the type of trauma. PMID- 7782797 TI - Stability of red blood cell membrane fatty acid composition after acute myocardial infarction. AB - Questionnaire-based assessment of dietary intake may be invalidated in case control studies by biases of recall, reporting or interviewing. Biomarkers, free of such biases, can be useful adjunct measures if they themselves are not affected by the event under investigation. Consequently, we studied the stability of the fatty acid composition of the red blood cell (RBC) membrane during a 1 week period, in 20 patients aged 40-74 years after an acute myocardial infarction (MI). Statistical analysis that accounted for a repeated measures design with missing data was undertaken for five fatty acids: C16:0, C18:1, C18:2, C20:5 and C22:6. All fatty acids showed change over the 7 day period. Individuals tended to maintain their relative ranking over time as reflected by correlations between time points of between 0.85 to 0.90, with the exception of C16:0 in which correlations were lower and inconsistent. Over the first 24 hr from admission all fatty acids except C20:5 showed evidence of a statistically significant change. However over the first 7 hr C18:1, C18:2, C20:5 and C22:6 exhibited stability whereas C16:0 altered. We conclude that the fatty acid composition of the RBC membrane appears to change soon after an acute MI. Consequently, case-control studies may be biased towards positive associations for C16:0 and inverse associations for C18:2 and C20:5, i.e. consistent with conventional predictions. However, if blood samples are drawn within 6 hr of admission, bias in estimation of C18:1, C18:2, C20:5 and C22:6 may be unimportant. PMID- 7782798 TI - Use of certainty of opinion data to enhance clinical decision making. AB - Clinical decision making and diagnostic testing procedures are frequently evaluated using indices such as sensitivity and specificity. These indices require an assumption that the underlying disease state or the diagnostic test result is binary, which may be an unreasonable assumption in many clinical situations. They also fail to recognise the potential for different degrees of diagnostic confidence. In this paper, we report some data from a clinical study of postpartum mothers in which, in addition to the diagnostic result, an expression of certainty or strength of belief was ascertained. We illustrate how the certainty of opinion data can be combined with the diagnostic opinion in order to enhance the interpretation of the study, and the implications for improving the accuracy of clinical decision making in general. PMID- 7782799 TI - The U-shaped association between body mass index and mortality: relationship with weight gain in a Native American population. AB - In order to determine whether weight loss explains high mortality rates in those with a low body mass index (BMI), the relationships between BMI, rate of weight gain and mortality were examined in Pima Indians. Subjects were 814 diabetic and 1814 nondiabetic participants in a longitudinal survey who had at least two examinations after age 20. Median duration of follow-up was 8.1 (range 0.03-25.1) years. BMI showed a U-shaped relationship with mortality rates in men with the lowest rates in the 30-35 kg/m2 category; an inverse relationship was seen in women. Subjects who were losing weight had higher mortality rates than those who were gaining. However, excess mortality among the lightest subjects was present among those who were gaining weight. Among nondiabetic subjects, the mortality ratio (MR) for BMI < 25 kg/m2 compared with 30-35 kg/m2 was 1.5 [95% confidence interval (CI) 1.0-2.2] unadjusted for weight gain, while the adjusted MR was 1.3 [95% CI 0.9-1.9]. Weight loss, which may reflect underlying illness, is associated with high mortality rates in Pima Indians but does not fully account for the high mortality in the lightest individuals. PMID- 7782800 TI - Selecting a patient characteristics index for the prediction of medical outcomes using administrative claims data. AB - Recently, there has been a great deal of discussion regarding the use of administrative databases to study outcomes of medical care. A major issue in this discussion is how to classify patients in terms of characteristics such as disease-severity, comorbidities, resource needs, stability, etc. Different indices have been developed in an attempt to provide a common classification scheme in terms of these characteristics. In this paper, we examine the utility of four indices in the prediction of length of stay and 30-day mortality for patients undergoing total knee replacement surgery between 1985 and 1989. The indices that we compare are the Deyo-adapted Charlson Index, the Relative Intensity Score derived from Patient Management Categories (PMCs), the Patient Severity Level derived from PMCs, and the number of diagnoses (up to five) listed in the Medicare claims data. The first three of these indices represent measures of comorbidity, resource use, and severity of illness, respectively. The number of diagnoses is likely to capture aspects of each of these characteristics. We find that all of the indices improve (in terms of model fit) over the baseline (no index) models of length of stay and mortality, and the Relative Intensity Score and Patient and Severity Level result in the greatest improvement in measures of model fit. We found, however, that these two indices have a non monotonic relationship with length of stay and mortality. The Deyo-adapted Charlson Index performed least well of the four indices in terms of explanatory ability. The number of diagnoses performed well, and does not suffer from problems associated with miscoding on claims data. PMID- 7782801 TI - Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. AB - The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis. PMID- 7782802 TI - The relation of reported symptoms to social, individual, and behavioral indicators of ill-health: is the number of reported symptoms a unique general dimension of ill-health? AB - Counts of functional symptoms are an accepted measure of ill-health in general populations. However, their relation to other indicators of ill-health are still poorly understood. The aim of this study was to investigate such relations in order to reach a better understanding of the 'meaning' of the number of symptoms. The data analyzed was drawn from a telephone health survey conducted among a representative sample of 2111 Swiss adults as part of the Intercantonal Health Indicators Project in 1989. In a logistic regression analysis the Number of symptoms (a summery score of eleven severe function symptoms) was found to be strongly associated with eight social, behavioral, and psychological indicators of ill-health ('Unable to work', 'Frequently consulting a physician', 'Use of analgesics', 'Use of sedatives', 'Poor coping with ill-health', 'Social impairment', 'Poor health', and 'Poor psychological well-being'). To control for effects due to individual symptoms, they were included in the models by stepwise procedure. Although individual symptoms became predictive for all indicators (except for Poor coping with illness), the association between the Number of symptoms and the indicators (except for Social impairment) remained statistically significant. Despite methodological provisos our results seem to support an interpretation of the Number of symptoms as a distinct and general dimension of ill-health. PMID- 7782803 TI - Re-scaling the Spanish version of the Sickness Impact Profile: an opportunity for the assessment of cross-cultural equivalence. AB - The Sickness Impact Profile (SIP), a behaviour-based measure of health status developed in the US, was adapted into Spanish. The aim of this study was to obtain the item weights of the Spanish version, to compare these weights with those of the original instrument, and to assess cross-cultural differences that may affect scale equivalence. Following the original work, weights for the Spanish items were obtained using the equal appearing intervals methodology in two groups of judges: 25 health professionals and 120 consumers. Correlation between professionals' and consumers' item weights was 0.93, thus data were combined for further analysis. Correlations between Spanish and American item weights was 0.89 (p < 0.001). Among each SIP category, correlations ranged from 0.61 to 0.99. Cultural differences were found among social items belonging to the social interaction category. While specific cultural differences exist when specific item weights were compared, overall cultural differences were not relevant. For practical purposes, the American and Spanish versions of the SIP should be considered cross-culturally equivalent. PMID- 7782804 TI - Serum prolactin levels and their relationship to survival in women with operable breast cancer. AB - The prognostic value of serum prolactin levels was assessed in a sequential series of 739 patients who were initially treated at Guy's Hospital, London, between 1975 and 1980. Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy. Follow-up of the patients was up to August 1992 giving 6139 women-years with a median follow-up time of 11.5 years (13.7 for patients still living and 5.1 for those dead). The association between the three prolactin variables and reproductive and clinical factors was examined before assessing the prognostic value of prolactin levels in terms of overall, disease-specific and disease-free survival. Multivariate survival models were used in order to adjust for the effect of other prognostic variables. These were found to be: tumour size, degree of nodal involvement, tumour grade and age at diagnosis. The results showed that high Hpr2 or high postoperative increase in prolactin (i.e. Hpr2-Hpr1) were significantly related to shorter disease-specific survival (p = 0.04 and 0.01, respectively) in postmenopausal women. In addition there was some indication, which did not attain formal significance, for this association to occur for disease-free survival. Thus the rise in blood prolactin levels after surgery may be a weak indicator of poor prognosis of breast cancer in postmenopausal women. PMID- 7782806 TI - The development of disability scales for childhood and adolescent injuries. AB - Scales for the study of injury-induced disabilities among 0-17 year olds were developed. Telephone interviews were conducted among parents of injured children (n = 432) 6 months after hospitalization in the three main hospitals of Jerusalem, about disabilities immediately following and 6 months after the injury. The scale for 4-17 year olds included 25 items derived from the International Classification of Disabilities, Impairments and Handicaps. Factor analysis revealed three dimensions of disability: personal care and daily activities; motor activities; and communication and sensory activities. The scale and the derived subscales on personal care and daily activities, and on motor activities showed high Cronbach's alpha, especially for disabilities immediately after the injury. The scale or subscales are easy to use, related to everyday activities performed by children in all cultures, are not related to the characteristics of the respondents, and have high consistency-reliability and construct validity. They may be used to assess the prevalence of disabilities in population studies. PMID- 7782805 TI - Wolfe's mammographic patterns in women with gross cystic disease of the breast. AB - The epidemiologic determinants of the mammographic pattern were studied in 710 patients with aspirated gross (> 1 ml) cysts of the breast. The prevalence of the mammograms classified as P2-DY, that are considered to be associated with an increased breast cancer risk, was 636/710 or 89.6%. No relationship between mammographic patterns and characteristics of breast cyst fluid such as K+/Na+ ratio, apocrine changes and dehydroepiandrosterone sulfate concentration was observed. A significant decrease in the proportion of these patterns with increasing age (p = 0.006), Quetelet Index (p < 0.001), parity (p = 0.001), and in postmenopausal women (p = 0.026) was found. Conversely, P2-DY patterns were significantly associated with a later age at menarche (p = 0.023) and alcohol consumption (p = 0.001). In multivariate analysis, an independent association with age was not observed whereas the associations with age at menarche, parity, and relative weight were confirmed. In conclusion, the epidemiologic determinants of mammographic patterns are the same in Gross Cystic Disease patients as in unaffected women, and the lack of correlation between mammographic pattern and cyst type suggests that the latter may represent an independent predictor of breast cancer risk. PMID- 7782807 TI - The demise of the randomized controlled trial. PMID- 7782808 TI - Pitfalls in assessing the effect of time-varying covariates in cross-sectional studies. PMID- 7782809 TI - Ethics in clinical practice. Introduction. PMID- 7782810 TI - Care: the basis for a nursing ethic? AB - This article takes issue with the position in the recent general and cardiovascular nursing literature that care is the foundation for nursing's professional ethic. This literature is critically examined to support the determination that care is necessary but insufficient. Care without cure is incomplete in any health care discipline, including nursing. Any nursing ethic will be inadequate if it does not integrate the care/relationship and cure/justice/individual foundations. PMID- 7782811 TI - The potential for noncaring when dealing with difficult patients: strategies for moral decision making. AB - The potential for noncaring when dealing with difficult patients is a very real concern in nursing. Noncaring, manifested by distancing and withdrawal or punitive behaviors, exacts a high toll on the nurse-patient relationship. Noncaring may result in missed diagnoses and interventions, social isolation, and minimal or negative contact with the nurse. The purpose of this article is to share strategies for moral decision making that support the patient, family, and nurse in all care settings. Decisions to care must be based on professional, ethical, and moral principles rather than personal preferences. Scrutinizing one's personal biases and actions with application of ethical principles provides the framework for these strategies. PMID- 7782812 TI - Case study: when the nurse and physician don't agree. AB - Nurses and physicians by virtue of their roles as health care professionals must work together to provide care for their patients. Decisions regarding life support and death and dying are made almost daily in most intensive care units. Conflicts frequently arise among health care providers when decisions of this nature are made. Nurses and physicians, despite having similar value systems, operate under a different frame of reference. Understanding the differences and how they play themselves out in the clinical setting can alleviate much of the stress and frustration common when these issues are encountered. This article examines the value systems and perspectives of nurses and physicians using a case study format. PMID- 7782814 TI - Going through the motions: the ethics of process. AB - This article takes the position that the current ethic of nursing is inadequate. It is limited to an ethic of process. This ethic limits the discipline of nursing to process-oriented activities, including research and the clinical nursing process. These processes are not, however, unique to nursing but are shared by all professional disciplines. Nursing will continue to be insufficient without the development of structure or expert clinical knowledge accompanied by an ethic of accountability. PMID- 7782813 TI - Are we promoting true informed consent in cardiovascular clinical trials? AB - The purpose of this study was to determine variables contributing to patient participation in randomized clinical trials while assessing the potential relationship of these variables to a valid consent process. Two hundred forty seven patients were administered a questionnaire after they made their decision about participation. Numerous variables were explored for their relationship to patient participation. Of particular significance were the variables of education, perception of having enough time to decide, and the person approaching the patient. Results of this study reveal the need for further evaluation of informed consent as a process, focusing on the areas of patient autonomy and comprehension. PMID- 7782816 TI - Resources for ethical decision making. AB - Nurses often encounter ethical dilemmas during the course of their practice and play a key role in the ethical decision-making process. This article identifies resources available to assist the nurse in making sound ethical decisions. Institution-based resources, such as institutional review boards and pastoral care, and unit-based resources, including nursing ethics rounds and peer support, are discussed. PMID- 7782815 TI - The nurse's role in end-of-life treatment discussions: preliminary report from the SUPPORT Project. AB - The methods of the Study to Understand Prognosis and Preferences of Outcomes and Risks of Treatment (SUPPORT), a five year, five-center study of decision making and communication in patients near the end of life, are described. Aspects of the study propose to describe the role of the staff nurse and the specially trained nurse facilitator in decision making in patients near the end of life. The nurse is in a unique position to initiate discussions about patient preferences for end of-life treatment and quality of life; however, a review of related research describes discordance between clinicians' understanding and patients' preferences for treatment. Ethical issues, practice barriers, and practice innovations in end of-life treatment are discussed. PMID- 7782817 TI - Persistence of 99mTc-labelled microorganisms on surfaces of impression materials. AB - Impression materials or prostheses can be contaminated with oral microflora and provide a significant source for cross-contamination. A study of such contamination was carried out using an approach different from that of infection control, which has often been investigated in previous studies. The study focused on microorganisms known to cause local and systemic diseases and which are normally found in the oral flora. The persistence of Streptococcus mutans (S. mutans), Escherichia coli (E. coli), Staphylococcus aureus and Candida albicans (C. albicans) on zinc-oxide eugenol, silicone rubber, irreversible hydrocolloid and polyether-rubber was investigated using 99mTc-labelled microorganisms. Ten specimens from each of the four impression materials were prepared as discs of 3 mm in height and 10 mm in diameter. After the specimens had been placed into a suspension of 99mTc-labelled microorganisms, remaining radioactivity was counted in a gamma counter. According to own findings, S. mutans was the most, and E. coli the least persistent on the specimen surfaces. The number of microorganisms removed after washing was less than the amount remaining on the surfaces. C. albicans was removed most easily from all impression surfaces that bore persistent microorganisms after washing. Other microorganisms showed various degrees of persistence according to the impression material. PMID- 7782818 TI - Surgical advancement of the mandible through sagittal ramus osteotomy. AB - The sagittal split-ramus osteotomy (SSRO) technique has gained widespread acceptance, for it can be easily adapted to correct a wide variety of mandibular abnormalities. However, in spite of its many advantages, numerous investigators have reported postoperative relapse following mandibular advancement surgery. SSRO was performed on four patients with deficiency of mandibular growth which had led to characteristic protrusion of the maxilla. In three of the four cases, postoperative skeletal relapse occurred, which was corrected by postoperative orthodontic treatment. PMID- 7782819 TI - Passive mandibular border positions and their relationships with signs and symptoms of craniomandibular disorder. A study of linear and angular measurements. AB - Linear measurements of passive mandibular border positions and angular measurements of passive opening were recorded in a group of patients with craniomandibular disorders. The relationships between signs and symptoms of craniomandibular disorders and abnormal capacity of movement were studied. There was significant association of some signs and symptoms related to the temporomandibular joint and abnormal vertical and horizontal excursions. On the other hand, there was only one relationship between occlusal factors and abnormal passive mandibular border positions. PMID- 7782820 TI - A study of cysts in the oral region. Cysts of the jaw. AB - Clinical cases of cysts of the jaw treated in the Department of Oral Surgery of our university during the 10 y between 1980 and 1989 were studied clinically. Patients with radicular cyst, dentigerous cyst, odontogenic keratocyst and postoperative maxillary cyst, which were found at relatively high frequencies, were further analyzed with regard to age, sex and anatomical distribution. A diagnosis of cyst was established in 1,444 patients during the above period, and 1,234 (85.5%) of them had cysts of the jaw. According to a pathological classification by Ishikawa's method, these patients included 509 (41.2%) with radicular cyst, 259 (27.0%) with dentigerous cyst, 95 (7.7%) with odontogenic keratocyst and 267 (21.6%) with postoperative maxillary cyst. The pattern of age distribution in cases of radicular cyst, odontogenic keratocyst and postoperative maxillary cyst was similar to that found in previous studies. Among patients with dentigerous cyst, those aged under 20 y accounted for about 60%. Radicular cyst occurred most frequently in the maxillary lateral incisors, dentigerous cyst in the mandibular wisdom teeth, and odontogenic keratocyst in the region between the mandibular molar and the ramus of the mandible. PMID- 7782821 TI - Effects of salivary immune response to Streptococcus mutans on caries occurrence and caries development in mice with autoimmune disease. AB - MRL/l strain mice, which possess a lymphoproliferative gene inducing swelling of systemic lymph nodes, develop a SLE (systemic lupus erythematosus)-like syndrome at around 8 w of age. MRL/n mice, which carry 99.6% of the genes of MRL/l mice, lack the gene for lymphoproliferation and exhibit only a slight degree of lymph node swelling late in life. This study investigated whether the salivary immune response caused by Streptococcus mutans(S. mutans) infection prevented dental caries in MRL/l and MRL/n mice after 8 w of age. A total of 10 MRL/l mice and 10 MRL/n mice were fed a commercial pellet diet without sucrose until 74 d of age, and then fed Diet 2000 containing 56% sucrose ad libitum from 75 to 130 d of age. On d 75, both strains of mice were inoculated with S. mutans JC-2 for 7 d. At 130 d of age, saliva samples were collected and caries scores were assessed. The results obtained suggested that the salivary immune response was one of the most important factors regulating caries occurrence. PMID- 7782822 TI - A study of temporomandibular joint sounds. Part 2. Acoustic characteristics of joint sounds. AB - In an attempt to gain a better understanding of temporomandibular joint (TMJ) sounds, we recorded joint sounds from 14 non-orthodontically treated dental students, analyzed the acoustic characteristics of the TMJ sounds, and correlated the sound characteristics with axiographic features, morphologic observations of X-ray images and clinical history. The group with a low peak frequency (< 500 Hz) of the opening click had a shorter history of subjective joint sound, a longer distance between the opening and closing curves, and a low rate of TMJ transformation. For the closing click, the history of subjective joint sounds tended to be longer when the duration of the wave was short. Acoustic analysis of TMJ sounds could be an aid to the differential diagnosis of temporomandibular disorders, although it is difficult to deduce the clinical history and internal deformities of the TMJ based solely on acoustic characteristics. PMID- 7782823 TI - Metrical differential diagnosis based on location. Differential diagnosis among various cysts. AB - An attempt was made to quantify the location of oral lesions. Panoramic radiographs of non-odontogenic cysts (13 globulomaxillary cysts, 8 median maxillary cysts, 8 nasopalatine cysts, 5 nasoalveolar cysts and 11 simple bone cysts) and odontogenic cysts (37 radicular cysts, 13 radicular granulomas, 68 dentigerous cysts and 40 odontogenic keratocysts) were examined. Metrical data (integers) were obtained from a conversion table and the abscissa values (to the first decimal place) were obtained from the centroid of the cysts. Differential diagnosis among these lesions revealed the following: 1. In the maxilla, it was possible to differentiate median maxillary cysts and nasopalatine cysts from globulomaxillary cysts, nasoalveolar cysts, radicular cysts, radicular granulomas, dentigerous cysts and odontogenic keratocysts. 2. In the mandible, it was difficult to differentiate simple bone cysts, radicular cysts, radicular granulomas, dentigerous cysts and odontogenic keratocysts from one another. The present findings revealed that data on lesion location can be changed into metrical data for differential diagnosis of cysts. PMID- 7782824 TI - Surgical management of spinal epidural hematoma: relationship between surgical timing and neurological outcome. AB - Thirty patients were treated surgically for spinal epidural hematoma (SEH). Twelve of these cases resulted from spinal surgery, seven from epidural catheters, four from vascular lesions, three from anticoagulation medications, two from trauma, and two from spontaneous causes. Pain was the predominant initial symptom, and all patients developed neurological deficits. Eight patients had complete motor and sensory loss (Frankel Grade A); six had complete motor loss but some sensation preserved (Frankel Grade B); and 16 had incomplete loss of motor function (10 patients Frankel Grade C and six patients Frankel Grade D). The average interval from onset of initial symptom to maximum neurological deficit was 13 hours, and the average interval from onset of symptom to surgery was 23 hours. Surgical evacuation of the hematoma was performed in all patients; 26 of these improved; four remained unchanged, and no patients worsened (mean follow up 11 months). Complete recovery (Frankel Grade E) was observed in 43% of the patients and functional recovery (Frankel Grades D or E) was observed in 87%. One postoperative death occurred from a pulmonary embolus (surgical mortality 3%). Preoperative neurological status correlated with outcome; 83% of Frankel Grade D patients recovered completely compared to 25% of Frankel Grade A patients. The rapidity of surgical intervention also correlated with outcome; greater neurological recovery occurred as the interval from symptom onset to surgery decreased. Patients taken to surgery within 12 hours had better neurological outcomes than patients with identical preoperative Frankel grades whose surgery was delayed beyond 12 hours. This large series of SEH demonstrates that rapid diagnosis and emergency surgical treatment maximize neurological recovery. However, patients with complete neurological lesions or long-standing compression can improve substantially with surgery. PMID- 7782825 TI - Pathological effects of angioplasty on vasospastic carotid arteries in a rabbit model. AB - To define the pathological effects of angioplasty on vasospastic arteries, 36 rabbits underwent angiography and induction of vasospasm by placement of blood filled (vasospasm groups) or empty (control group) silastic sheaths around the cervical carotid arteries. Two (Day 2) or 7 days (Day 7) later, angiography was repeated and one carotid artery in each animal was dilated by balloon angioplasty. The rabbits were sacrificed 1 day, 7 days, or 3 to 4 weeks after angioplasty. Significant vasospasm developed after placement of silastic sheaths with blood (mean reductions in diameter 39% +/- 6% at Day 2 and 48% +/- 5% at Day 7). Arterial narrowing was less apparent in the control groups at Day 2 (24% +/- 7%). Angioplasty performed on Day 2 significantly increased arterial diameters of vasospastic arteries (50% +/- 7%; p < 0.05) but not those of control arteries (10% +/- 6%, p > 0.05). Angioplasty performed on Day 7 increased the arterial diameters by a similar degree (47% +/- 13%, not significant). Arteries remained dilated after angioplasty, although there was significant vasospasm 7 days after angioplasty when angioplasty was performed on Day 2. Blinded, semiquantitative histopathological study of the arteries showed that 3 to 4 weeks after angioplasty, there was significant endothelial proliferation and a trend for thinning of the tunica media. There were no significant changes in control arteries subjected to angioplasty. Angioplasty was not associated with significant arterial fibrosis as measured by hydroxyproline content (analysis of variance). The increase in endothelial proliferation and decrease in the thickness of the tunica media suggest that, in the rabbit model, angioplasty damages endothelial and smooth-muscle cells. This may be the basis for the observation that vasospastic arteries do not reconstrict after angioplasty. PMID- 7782826 TI - Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage. AB - The continuous release of nitric oxide (NO) is required to maintain basal cerebrovascular tone. Oxyhemoglobin, a putative spasmogen, rapidly binds NO, implicating loss of NO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). If vasospasm is mediated by depletion of NO in the vessel wall, it should be reversible by replacement with NO. To investigate this hypothesis, the authors placed blood clots around the right middle cerebral artery (RMCA) of four cynomolgus monkeys; four unoperated animals served as controls. Arteriography was performed before and 7 days after surgery to assess the presence and degree of vasospasm, which was quantified in the anteroposterior (AP) projection by computerized image analysis. On Day 7, cortical cerebral blood flow (CBF) in the distribution of the right MCA was measured during four to six runs in the right internal carotid artery (ICA) of brief infusions of saline followed by NO solution. Arteriography was performed immediately after completing the final NO infusion in three of the four animals with vasospasm. Right MCA blood flow velocities were obtained using transcranial Doppler before, during, and after NO infusion in two vasospastic animals. After ICA NO infusion, arteriographic vasospasm resolved (mean percent of preoperative AP area, 55.9%); that is, the AP areas of the proximal portion of the right MCA returned to their preoperative values (mean 91.4%; range 88%-96%). Compared to ICA saline, during ICA NO infusion CBF increased 7% in control animals and 19% in vasospastic animals (p < 0.002) without significant changes in other physiological parameters. During NO infusion, peak systolic right MCA CBF velocity decreased (130 to 109 cm/sec and 116 to 76 cm/sec) in two vasospastic animals. The effects of ICA NO on CBF and CBF velocity disappeared shortly after terminating NO infusion. Intracarotid infusion of NO in a primate model of vasospasm 1) increases CBF, 2) decreases cerebral vascular resistance, 3) reverses arteriographic vasospasm, and 4) decreases CBF velocity in the vasospastic artery without producing systemic hypotension. These findings indicate the potential for the development of targeted therapy to reverse cerebral vasospasm after SAH. PMID- 7782827 TI - Effects of potassium channel activators on isolated cerebral arteries of large and small diameter in the cat. AB - The smooth-muscle relaxant action of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in cerebral arteries of large diameter has been confirmed in a number of in vitro studies, but there is still debate about the presence of KATP channels in small cerebral arteries. In the present study, the authors compare the effects of cromakalim and bimakalim, two putative KATP channel activators, in different parts of the feline isolated middle cerebral artery (MCA) designated proximal, intermediate, and distal. The latter corresponds to those small pial arteries that are usually studied in vivo. In ring segments precontracted with 10(-5) M of uridine-5-triphosphate (UTP), both cromakalim and bimakalim induced concentration-related relaxation, with bimakalim being more potent than cromakalim, and no significant differences noted among segments obtained from the different regions of the MCA. In vessels precontracted by adding 30 mM KCl the potency of cromakalim and bimakalim was reduced compared with that obtained after UTP precontraction. In the presence of 10(-6) M glibenclamide, an antagonist of KATP channel activators, the concentration-effect curve to bimakalim was shifted to the right in the proximal and distal MCA, indicating a similar route of action for bimakalim and cromakalim in these arteries. The present study therefore indicates the presence of KATP channels in isolated small cerebral arteries according to results obtained in vivo. Activators of KATP channesl may prove helpful in the treatment of vasospasm, which may occur in large and small cerebral arteries after subarachnoid hemorrhage. PMID- 7782828 TI - Histological findings in giant aneurysms treated with Guglielmi detachable coils. Report of two cases with autopsy correlation. AB - The authors report the pathological and histological findings in two patients with giant partially thrombosed aneurysms who were treated by means of Guglielmi detachable coils with subtotal occlusion of the aneurysms. Autopsies of these patients were performed 2 and 6 months after endovascular treatment. The histological findings revealed coils embedded in largely unorganized thrombus in the aneurysms; there was no clear reduction in size of the aneurysms over the period. There was no evidence of endothelialization of the aneurysm neck demonstrated in either case. The significance of these findings is discussed. PMID- 7782829 TI - Ossification of the anterior longitudinal ligament and Forestier's disease: an analysis of seven cases. AB - A retrospective review was conducted on the records and radiographs of six symptomatic patients and one asymptomatic patient with Forestier's disease. No other series of patients with this disease is found in the neurosurgical literature. Forestier's disease, also known as diffuse idiopathic skeletal hyperostosis (DISH), is an idiopathic rheumatological abnormality in which exuberant ossification occurs along ligaments throughout the body, but most notably the anterior longitudinal ligament of the spine. It affects older men predominantly; all of our patients were men older than 60 years of age. The disease is usually asymptomatic; however, dyspnea, dysphagia, spinal cord compression, and peripheral nerve entrapment have all been documented in association with the disorder. Five of the six symptomatic patients presented with dysphagia due to esophageal compression by calcified anterior longitudinal ligaments, and one patient developed recurrent spinal stenosis when scar tissue from a previous decompressive laminectomy became calcified. All patients responded well to surgery. Two of the four patients who underwent removal of cervical osteophytes required several months following surgery for the dysphagia to resolve. This would support the hypothesis that not all cases of dysphagia in Forestier's disease are due to mechanical compression. Dysphagia may result from inflammatory changes that accompany fibrosis in the wall of the esophagus or from esophageal denervation. Evaluation of dysphagia even in the presence of Forestier's disease must rule out occult malignancy. The authors' experience suggests that dysphagia in the setting of Forestier's disease is an underrecognized entity amenable to surgical intervention. PMID- 7782831 TI - Aneurysm of a persistent primitive olfactory artery. Case report. AB - A ruptured anterior cerebral artery (ACA) aneurysm is reported in a patient in whom an anomalous ACA arose from the internal carotid artery at the bifurcation. The aberrant artery coursed anteriorly along the ipsilateral olfactory tract and made a hairpin turn posterior to the olfactory bulb, supplying the circulation of the ACA. Persistence of the primitive olfactory artery is suggested as an embryological origin of this vascular anomaly. PMID- 7782830 TI - Imaging studies of cerebral hyperperfusion after carotid endarterectomy. Case report. AB - A case is reported of severe unilateral hemispheric edema and localized hemorrhage associated with seizures following endarterectomy of an ipsilateral high-grade carotid stenosis. Imaging studies including angiography, computerized tomography (CT), magnetic resonance imaging/angiography, and xenon-CT, suggested postoperative ipsilateral cerebral hyperperfusion. Cerebral hyperperfusion syndromes caused by a probable failure of vascular autoregulation are rare but potentially serious complications after endarterectomy. The literature on this type of complication is briefly reviewed, and the role of various imaging modalities in identification of the syndrome and in guiding management decisions is emphasized. PMID- 7782832 TI - Association of venous and true arteriovenous malformation: a rare entity among mixed vascular malformations of the brain. Case report. AB - In this article the authors report the case of a mixed cerebrovascular malformation in which a true arteriovenous malformation (AVM), harboring a nidus, is associated with a venous malformation that serves as the draining vein for the nidus. Despite the authors' preoperative rationale for exclusive extirpation of the AVM, an inadvertent injury and the obliteration of the venous malformation generated delayed postoperative neurological deterioration, which could clearly be attributed to venous hemorrhagic infarction. Because this is only the second instance of this type of mixed vascular malformation of the brain reported, which also underscores the concept of nonsurgical treatment of venous malformations, the authors discuss the diverse literature regarding mixed vascular malformations and the treatment of venous malformations. PMID- 7782833 TI - Melanotic neuroectodermal tumor of infancy: a molecular approach to diagnosis. Case report. AB - A case of melanotic neuroectodermal tumor of infancy arising from the transverse sinus is presented. The tumor was located on the outer surface of the dura and extended extracranially through the occipitomastoid suture. Two cell populations were observed: pigmented melanocyte-like cells and small neuroblast-like cells. Ultrastructural analysis revealed epithelial tumor cells and melanosomes at various stages. Expression of melanotransferrin messenger RNA transcripts within the tumor tissue was observed using a reverse transcriptase-polymerase chain reaction method in addition to immunohistological studies. The positive expression of melanotransferrin confirmed that this melanotic neuroectodermal tumor was derived from neural crest cells. PMID- 7782834 TI - Metachronous ovarian dysgerminoma after a suprasellar germ-cell tumor treated by radiation therapy. Case report. AB - A case of suprasellar germ-cell tumor in a 9-year-old girl who later developed ovarian dysgerminoma is reported. The clinical course of the case is described and a double-primary tumor, rather than metastasis from either tumor to the other, is suggested by the authors to explain the oncogenesis in this patient. The authors strongly encourage that patients with intracranial germinoma be examined for associated extraneural lesions before, as well as after, the completion of the initial therapy. PMID- 7782835 TI - Radiation-induced gliosarcoma. Case report and review of the literature. AB - A 13-year-old boy presented with a cerebral gliosarcoma 12 years after having acute lymphoblastic leukemia treated by chemotherapy and central nervous system prophylaxis treated by radiation therapy (24 Gy) and intrathecal methotrexate. A review of the literature disclosed 129 possible radiation-induced gliomatous and/or sarcomatous brain tumors: namely, 89 gliomas, 36 sarcomas, and four gliosarcomas, including the present case. An analysis of these cases revealed several characteristics that differentiate them from similar spontaneous brain tumors, thus providing arguments for the carcinogenic effect of radiation therapy on intracranial tumors. PMID- 7782836 TI - Functional thalamic depression in a case of reversible central pain due to a spinal intramedullary cyst. Case report. AB - In this report the authors discuss a case of central pain of spinal cord origin due to a spinal thoracic intramedullary cyst. Single-photon emission computerized tomography with technetium-99m hexamethylpropyleneamineoxime showed thalamic hypoperfusion contralateral to the affected leg. Surgical evacuation resulted in total relief of the pain and normalization of the thalamic alteration. The reader can infer from these findings that functional alterations in thalamic processing may be important in the genesis of central pain. PMID- 7782837 TI - Symptomatic cerebellar metastasis and late local recurrence of a cauda equina paraganglioma. Case report. AB - This case report contains a description of a 61-year-old patient who presented with a progressive truncal ataxia 22 years after complete removal of a small paraganglioma of the cauda equina. Magnetic resonance imaging of the neuraxis revealed a large cystic lesion in the cerebellar midline, three small cortical-to subcortical nodular tumors in the posterior fossa, and local recurrences of the paraganglioma of the cauda equina. Pathological examination showed the cerebellar midline lesion to be a paraganglioma, most likely a metastasis from the cauda equina localization. PMID- 7782839 TI - Crossroads at Salerno: Eldridge Campbell and the writings of Theodorico Borgognoni on wound healing. AB - During Eldridge Campbell's tour of duty as the neurosurgical consultant to the Mediterranean theater of World War II operations, he was introduced to a then revolutionary method of wound treatment. Ironically, Campbell's diligent research efforts later revealed that this method of wound treatment had first been advocated seven centuries earlier--in the same geographical location--by the Italian surgeon Theodoric. Although controversial, this method of wound care was subsequently applied and supported by Theodoric's outspoken pupil, Henri de Mondeville, despite intense opposition from the prevailing medical authorities who supported the doctrine of "laudable pus" for wound management. With Mondeville's death, Theodoric's technique lapsed into obscurity, relegated to a historical footnote until modern biology and the discoveries of Lister and Pasteur would again bring to light the benefits of nonsuppurative wound treatment. In this article the author discusses the work of Theodoric, Mondeville, and Campbell in light of the medical climate of their times and explores the contemporary parallels noted by Campbell in terms of the neglect of other, more recent medical discoveries. These examples encourage us to accept or reject medical treatments based on a thorough examination of their efficacy and not on the stature of their advocates within the medical community. PMID- 7782841 TI - Right-angle clip applier. PMID- 7782838 TI - Histologically verified cerebral aneurysm formation secondary to embolism from cardiac myxoma. Case report. AB - Multiple aneurysm formation secondary to an embolism from the cardiac myxoma is a well-known phenomenon. The cerebral arterial aneurysm formation process involved remains to be elucidated, although occupation of the arterial wall by tumor cells has been proven histologically. The authors present the case of a patient in whom tumor cells in the aneurysm wall were demonstrated and penetration of viable myxoma cells into the wall was also observed 19 months after surgical removal of the cardiac tumor. Such findings have never before been verified histologically. In light of the histological findings, the authors discuss the therapeutic problems associated with cerebral aneurysms resulting from cardiac myxoma. PMID- 7782840 TI - Relationship of intraoperative electrophysiological criteria to outcome after selective functional posterior rhizotomy. AB - At British Columbia's Children's Hospital, the criteria used in selective functional posterior rhizotomy (SFPR) evolved in three distinct phases. In Phase 1 the electrophysiological criteria for abnormality included a low threshold to a single stimulation, a sustained response to 50-Hz stimulation, and spread outside the segmental level being stimulated. In Phase 2 the electrophysiological criteria were unchanged, but fewer L3-4 nerve roots were cut. In Phase 3, fewer L3-4 nerve roots were cut, as in Phase 2, but based on the results of posterior nerve root stimulation in nonspastic controls, the only electrophysiological criterion used was contralateral and suprasegmental spread. The present study examined the relationship between the criteria used in each phase and patient outcome. The records of 77 consecutive children who underwent SFPR and had a minimum follow-up period of 1 year were reviewed, comprising 25, 19, and 33 patients in Phases 1, 2, and 3, respectively. Outcome parameters included quantitative assessments of lower-limb spasticity and range of motion, and qualitative assessments of lower-limb function. In Phase 3, 52% of the nerve roots were cut, compared to 66% in Phases 1 and 2. In all three phases there was a significant decrease in lower-limb spasticity and an increase in range of movement, with the smallest decrease in spasticity in Phase 3. Over 90% of children in each phase improved with respect to lower-limb function, and excluding independent walkers and quadriplegics confined to a wheelchair, improvement in the level of ambulation occurred in 87.5%, 71.4%, and 73.7% of patients, in Phases 1, 2, and 3, respectively. PMID- 7782842 TI - Microvascular decompression for trigeminal neuralgia. PMID- 7782843 TI - Compliments to NIH. PMID- 7782844 TI - Terminal syringomyelia and anorectal anomalies. PMID- 7782845 TI - Measurement of exercise tolerance on the treadmill in patients with symptomatic lumbar spinal stenosis: a useful indicator of functional status and surgical outcome. AB - A prospective study of patients with neurogenic claudication and lumbar spinal stenosis was undertaken to determine whether measurement of exercise tolerance on the treadmill would be useful in defining baseline functional status and response to surgical treatment. Twenty patients with an average age of 73 years, all of whom had intractable neurogenic claudication and radiographically confirmed severe lumbar spinal stenosis, were studied. Lumbar decompressive laminectomy was performed in all patients. Preoperatively and 2 months postoperatively, quantitative assessment of ambulation was conducted on a treadmill at 0 degree ramp incline at two different speeds: 1.2 mph and the patient's preferred walking speed. The following information was recorded: time to first symptoms, time to severe symptoms, and nature of symptoms (leg pain, back pain, or generalized fatigue). The examination was stopped after 15 minutes or at the onset of severe symptoms. In the preoperative 1.2-mph trial, the mean time to first symptoms was 2.68 minutes (median 1.31) and the mean time to severe symptoms was 5.47 minutes (median 3.42). In the postoperative trial at the same speed, 13 patients (65%) were able to walk symptom free for 15 minutes. The mean time to first symptoms was 11.12 minutes (median 15) and the mean time to severe symptoms was 11.81 minutes (median 15). Similar findings were recorded in the preferred walking speed trials. There were no complications from the treadmill testing procedure. These findings indicate that exercise stress testing on a treadmill is a safe, easily administered, and quantifiable means of assessing baseline functional status and outcome following laminectomy in patients with symptomatic lumbar spinal stenosis. PMID- 7782846 TI - Long-term follow up of 57 patients undergoing automated percutaneous discectomy. AB - Automated percutaneous discectomy has been performed in 57 patients at the author's institution since 1989, representing 4% of all lumbar spine surgeries. All 57 patients had unilateral sciatica. There were 33 women and 24 men ranging from 24 to 49 years of age, with a mean age of 45 years. All patients underwent computerized tomography (CT) in the prone position and CT and magnetic resonance imaging in the supine position. Diffuse versus eccentric disc bulging was determined for each patient. Four patients underwent surgery at the L3-4 level, four at L5-S1, and 49 at L4-5. One L5-S1 case could not be cannulated and surgery was aborted. There have been no complications related to surgery. Fifty patients (88%) stated they had reduced sciatica in the first 2 postoperative weeks. Forty (70%) had reduced sciatica 2 months postoperatively. The mean follow-up period was 27 months (range 6 to 45 months), with no patient lost to follow up. At their last follow-up examination, 33 patients (58%) showed improvement in their sciatica but only three (5%) were completely pain free. Of the 17 recurrences of sciatica, 11 patients have undergone microdiscectomy, with eight showing improvement. Chi-square analysis demonstrated a significantly better chance of improvement in patients with discs bulging eccentrically to the side of sciatica (p < 0.05) compared to patients with diffusely bulging discs. Automated percutaneous discectomy is safe and in selected patients can reduce sciatica, but only completely eliminated sciatica in 5% of patients with a follow-up period of 2.5 years. PMID- 7782847 TI - Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm. AB - Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had difuse or localized thick subarachnoid blood clots, two had diffuse thin clots and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome. PMID- 7782848 TI - Current implications for the efficacy of noninvasive screening for occult intracranial aneurysms in patients with a family history of aneurysms. AB - Although the technology exists for accurate noninvasive screening for intracranial aneurysms, the efficacy of screening depends on several key parameters of the natural history of aneurysms. Recent studies suggest that the prevalence of intracranial aneurysms may reach 20% in the subpopulation of patients with a family history of these lesions; other key parameters are less certain. The authors investigated factors that impact the efficacy of screening to establish interim guidelines. Three plausible models for the natural history of aneurysms were constructed. For each model the monetary cost of screening and the average gain in life expectancy were computed for a range of screening ages and prevalence rates. It is shown that the efficacy of screening depends on the pattern of aneurysm rupture. If aneurysms develop and rupture rapidly, then screening has no benefit. On the other hand, if aneurysms remain at risk for some time after formation, then screening may improve average life expectancy depending on when it occurs. The authors recommend that patients with a positive family history of aneurysms who are 30 years of age or younger be screened. This recommendation is based on the belief that the gains attributable to screening, assuming a constant rupture rate, outweigh the losses attributable to screening using a decreasing rupture rate model. PMID- 7782849 TI - A clinical and neuroradiological study of X-linked hydrocephalus in Japan. AB - To clarify the clinicopathological features of X-linked hydrocephalus, the authors studied 30 affected males from 15 families. In utero ultrasonography, performed at 21 to 40 weeks of gestation, revealed 18 fetuses with hydrocephalus. Computerized tomography (CT) revealed bilateral enlargement of the lateral ventricle with preponderant dilation of the posterior horn. In five patients with complete magnetic resonance (MR) imaging data, the most specific finding was localized atrophy of the anterior vermian lobe. Other MR imaging findings included a large massa intermedia, flat corpora quadrigemina, a small brainstem, and diffuse hypoplasia of the cerebral white matter. In all cases, the corpus callosum was hypoplastic or aplastic. The aqueduct was patent in four of five cases. Asymmetrical reduction of the ventricular size and a rippled ventricular wall were characteristic postshunt CT findings. Progressive macrocephaly and symptoms due to increased intracranial pressure were ameliorated by the shunt; however, the neurological outcome was not improved by shunting. Of 14 patients who lived to be between 2 and 18 years of age, all are retarded. These results indicate that X-linked hydrocephalus is not a disease of simple ventriculomegaly due to aqueduct stenosis alone but involves other complicated central nervous system anomalies. PMID- 7782851 TI - The anatomy of epileptic auras: focal pathology and surgical outcome. AB - An aura is generally understood to be the beginning of a seizure. Yet, following successful surgery for intractable epilepsy, patients may have persistent auras even though they are otherwise seizure free. Ninety patients with intractable seizures and auras underwent resective surgery. Forty-three patients had hippocampal sclerosis and 47 had temporal or extratemporal lesions such as glial tumors or vascular malformations. The semiology of the auras was found to have value in localization but not lateralization of the pathology. Epigastric auras as well as gustatory and olfactory auras were significantly more frequent in patients with hippocampal sclerosis than in those with temporal or extratemporal lesions. Auras of vertigo or dizziness were most frequent in patients with extratemporal pathology. There was a significant difference between the pathology groups in the efficacy of resection in eliminating the auras. Of the patients with hippocampal sclerosis who were rendered seizure free, 18.9% had persistent auras, whereas only one (2.6%) of the patients with temporal or extratemporal lesions who were rendered seizure free had persistent auras. These findings suggest that for patients with hippocampal sclerosis an anatomical dissociation between seizure and aura may occur, whereas this dissociation is not present in patients with lesions. Patients suspected of having hippocampal sclerosis should be counseled preoperatively as to the significant likelihood of persistent auras even if seizures are successfully abolished. PMID- 7782850 TI - Natural history of intracranial cavernous malformations. AB - The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations. PMID- 7782853 TI - Electrical stimulation of the trigeminal nerve root for the treatment of chronic facial pain. AB - Between March 1990 and December 1992, 23 patients with chronic intractable facial pain due to various forms of injury to the trigeminal nerve or nerve root underwent implantation of an electrical stimulating system to treat their pain. All patients had failed previous extensive pain treatment efforts. A monopolar platinum-iridium electrode was implanted on the trigeminal nerve root via percutaneous puncture of the foramen ovale. All patients experienced at least 50% reduction in pain intensity during a period of trial stimulation and underwent internalization of the electrode and connection to a completely implanted pulse generator. Independent assessment of the effect of stimulation was obtained by a specially trained nurse practitioner. Over a mean follow-up period of 24 months, six patients reported nearly complete relief of pain and six others reported at least a 50% reduction in pain intensity using a visual analog scale. Thus, 12 (52%) of the 23 patients achieved 50% or greater reduction in pain intensity. Although changes in the patterns of analgesic medication usage were few, six patients (26%) now experience a normal life style. Only one complication was seen, namely a dislocated electrode, which was easily replaced. Chronic electrical stimulation of the trigeminal nerve root appears to be an easy and safe technique for providing relief of chronic facial pain related to injury to the trigeminal nerve in a significant number of patients. PMID- 7782852 TI - Low-grade astrocytoma with neuraxis dissemination at diagnosis. AB - Little is known about low-grade astrocytoma with neuraxis dissemination at diagnosis. A review of medical records identified this phenomenon in eight of 150 pediatric patients evaluated between 1985 and 1994 for histologically confirmed low-grade astrocytoma. These patients (five male and three female) ranged in age from 5 months to 20 years (median 8 years). Symptoms of neuraxis disease were minimal or absent. Primary tumor sites were the hypothalamus in four cases, brainstem/spinal cord in three, and temporal lobe in one. Patterns of dissemination (evaluated by computerized tomography and/or magnetic resonance imaging techniques) appeared to be related to the primary site: hypothalamic tumors metastasized along the ventricular cerebrospinal fluid pathways, and tumors in other locations disseminated along subarachnoid pathways. Following initial treatment with chemotherapy (in three), partial resection (in one), radiation therapy (in three), and chemotherapy plus irradiation (in one), four patients required salvage therapy for progressive or recurrent disease. Seven of the eight patients are alive with stable or progressive disease 6 to 105 months postdiagnosis (median 15 months). Low-grade astrocytoma with initial neuraxis dissemination is responsive to chemotherapy and radiation, a proportion showing periods of stable disease. The optimum therapy or combination of therapies remains unclear. PMID- 7782854 TI - Performance of sulfhydryl boron hydride in patients with grade III and IV astrocytoma: a basis for boron neutron capture therapy. AB - This study investigated the rationale of boron neutron capture therapy (BNCT) for the treatment of Grade III and IV astrocytoma. The European Community joint research program on BNCT plans to use sulfhydryl boron hydride (BSH) in clinical trials. The work presented here, examines the performance of BSH in eight patients with Grade III and IV astrocytoma using a measurement technique which precisely correlates the boron uptake with the histology of the tumor and the peritumoral brain. Astrocytomas are exceptionally heterogeneous and spread migrating tumor cells into the surrounding brain. The patients were infused with 50 mg BSH per kilogram of body weight at 12, 18, 24 or 48 hours before surgery. At the time of operation, specimens were obtained of the tumor, skin, muscle, dura, blood, urine, and, when surgically possible, the brain adjacent to tumor. In three patients the intracellular boron distribution was investigated by subcellular fractionation. The blood clearance was biphasic with half-lives of 0.6 and 8.2 hours. After 3 days, approximately 70% of the dose injected was excreted in the urine. The maximum boron concentration in the tumor was 20 ppm, 12 hours after the infusion. The tumor-to-blood ratios ranged between 0.2 and 1.4, with the highest values after 18 to 24 hours. In the brain specimens the boron concentration never exceeded 1 ppm. This work confirms a selective uptake of boron in the tumor compared to the surrounding brain and that boron, to some extent, is incorporated in the tumor cells. PMID- 7782855 TI - Evidence for segregated pain and temperature conduction within the spinothalamic tract. AB - The lateral spinothalamic tract, located in the anterolateral quadrant of the white matter of the spinal cord, is one of the most important structures in transmitting pain within the central nervous system. It has been known for almost a century that destruction of fibers in this tract results in analgesia contralateral to the lesion. The effectiveness and clinical importance of interruption of the lateral spinothalamic tract has been proven in many studies. Today cordotomies are still a useful neurosurgical treatment modality, especially when pain can no longer be sufficiently controlled by analgesic drugs. Although analgesia on the contralateral side is the desired effect, one must also expect to cause disturbance in temperature sensation when performing a cordotomy. The authors' observations showed that after a cordotomy the dermatome level of analgesia can be variable within certain limits, which is in accordance with the literature. Surprisingly, however, the loss of temperature sensation may differ significantly from the loss of pain sensation. It was also found to be possible to perform a successful cordotomy without altering the sensation of temperature at all. This indicates that pain and temperature sensations may be conducted via separate pathways. Possible mechanisms underlying this phenomenon are discussed. PMID- 7782859 TI - Non invasive recording of CO2 cerebrovascular reactivity in normal subjects and patients with unilateral internal carotid artery stenosis. AB - CO2 cerebrovascular reactivity has been recorded in 12 healthy volunteers and 10 patients with unilateral > 70% extracranial internal carotid artery (ICA) stenosis, using non invasive techniques. The relative changes of middle cerebral artery blood flow velocity (VMCA) and velocity waveform pulsatility (PIMCA) after that hypocapnia was induced by spontaneous hyperventilation were recorded. 35.5% average VMCA reduction and 63% PIMCA increment of basal values was produced in healthy subjects after hyperventilation. The percentage variation of CO2 Reactivity Index (RI), expressed in terms of VMCA (V-RI) and PIMCA (PI-RI), per mmHg change in pCO2, presents a good right-left side correlation (r = 0.82 and r = 0.83 respectively) in healthy subjects, while a dissociation between V-RI and PI-RI was found in our patients. A significant reduction of PI-RI was also recorded in the group of patients on the side of ICA stenosis. From our data CO2 reactivity index recorded in terms of PI seems to allow a better separation between pathology and normality, without the need to assume a close relationship between velocity and blood flow under the condition considered. Furthermore, PI RI seems to be a valid index in the evaluation of some attribute pertaining to the distal vascular bed. PMID- 7782856 TI - A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model. AB - Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci. PMID- 7782860 TI - Primary optic nerve sheath meningiomas. Report of seven cases (clinical neuroradiological, pathological and surgical considerations in seven cases). AB - Between 1985 and 1993, we treated seven cases of optic nerve sheath meningiomas. The median age at onset of their symptoms was 42.14 years. All of the patients were aged between 27 and 60 females with a slowly progressive lesion. Computed tomography and/or magnetic resonance imaging were used as diagnostic procedure in our cases. We operated on using microsurgical techniques in all of these cases. Vision was preserved in the three of our cases. The definitive treatment for these lesions is surgical resection, although no single best plan for optimal management has been determined. The data indicate that only small anterior tumors may be removed with preservation of useful vision. With posterior circumferential tumors, there have been no cases of tumor removal with preservation of vision. A management strategy directed toward preservation of vision is discussed. PMID- 7782858 TI - Attenuation of postischemic brain hypoperfusion and reperfusion injury by the cyclooxygenase-lipoxygenase inhibitor BW755C. AB - Arachidonic acid metabolites are believed to be important mediators of tissue injury during reperfusion after cerebral ischemia. To determine whether inhibiting the oxygen-dependent metabolism of arachidonic acid would reduce reperfusion injury, we administered the mixed cyclooxygenase-lipoxygenase inhibitor BW755C (3-amino-1-[m(trifluoromethyl)phenyl]-2-pyrazoline) near the time of reperfusion in a rat model of temporary focal ischemia. The duration of ischemia + reperfusion was 2 hours + 22 hours, 3 hours + 3 hours, or 3 hours + 21 hours. The effects of drug or saline treatment on infarct volume, blood-brain barrier permeability, and blood flow were determined. Cortical blood flow was monitored with laser Doppler flowmetry and blood-brain barrier permeability was evaluated by the Evans blue dye method. Infarct volume was determined in all groups by computerized image analysis of Nissl-stained sections. We found that BW755C treatment significantly attenuated delayed postischemic hypoperfusion in the 3 + 3 group (p < 0.05) and reduced the volume of Evans blue dye staining in the cortex (p < 0.01) and basal ganglia (p < 0.05). Hemispheric swelling was reduced in all treatment groups (p < 0.01), as was total infarct volume in the ischemic hemisphere (p < 0.05). These results support the hypothesis that arachidonic acid metabolites contribute to acute postischemic reperfusion injury and suggest that using a mixed cyclooxygenase-lipoxygenase inhibitor as an adjunct to thrombolytic or revascularization therapy could lengthen the ischemia time after which reperfusion is beneficial. PMID- 7782857 TI - Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats. AB - To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33 degrees C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery. PMID- 7782861 TI - Cerebrospinal fluid shunt infections. AB - Cerebrospinal fluid (CSF) shunt infection is one of the most frequent and disabling complications. We reviewed the records of 306 patients who underwent CSF shunt surgery from 1983 through 1992. Six hundred and twelve procedures were performed in these 306 patients. Infection occurred following 46 of the procedures for an infection rate of 7.5% per procedure. The 46 infections involved 39 patients. There were 8 recurrent infections. The infection rate per child was 12.7%. Staphylococcal species were isolated in 50% of all infections. Patients younger than 1 year old and children with multiple revisions have a greater risk of infection than those of older. Myelomeningocele and meningitis had higher infection rate among other etiologies. Patients with multiple revisions had higher infection rate than those with single revision or none. The incidence of infection was higher in cyst-peritoneal shunts than both ventriculo atrial and ventriculo-peritoneal shunts. Mortality was high in Gram negative infections. PMID- 7782862 TI - Intraventricular pneumocephalus after posterior fossa and CSF shunting surgery. Case report. AB - The authors report a case of tension intraventricular pneumocephalus developed six months after the removal of an acoustic neuroma and a CSF ventriculoperitoneal shunt procedure due to a concomitant hydrocephalus. A review of the literature show only 19 cases of CSF shunt complicating pneumocephalus. The authors discuss both about the etiology of pneumocephalus and its therapeutic options. In our case we were unable to preoperatively localize the cranial base communication allowing intracranial air antry. The literature show however that eroded or thinned bone areas may be multiple and even diffuse their development depending upon several factors. We suggest in these cases a direct surgical repair through a craniotomy, as reported by others, is not mandatory. According to the etiology of pneumocephalus a temporary extraventricular drainage and the revision of the shunting pressure regimen may represent an effective treatment of this complication. PMID- 7782863 TI - Spinal epidermoid cysts without congenital anomalies associated. Report of two cases. AB - MR findings in two patients with intradural spinal epidermoid tumors without spinal anomalies are reported. In one case this tumor was congenital, the other one was considered iatrogenic. Origin and MR characteristics of this lesion are discussed. PMID- 7782864 TI - Bilateral traumatic abducens nerve palsy. Case report. AB - Bilateral traumatic abducens nerve palsy after head injury is a rare event. We present a case associated with skull fractures and intracranial hematoma, with complete recovery of abducens nerve palsy after six months. The mechanism of the lesion, the clinical conditions and the radiological findings are presented. PMID- 7782865 TI - Neurinoma of the cauda equina misdiagnosed as prolapsed lumbar disk. Report of three cases. AB - The authors report three cases of neurinoma of the cauda equina initially misdiagnosed as prolapsed lumbar disk. Computed Tomography failed to reveal the tumour, while showing evidence of disk-degenerative patology and being thus misleading. Similar cases are reported in literature. After a thorough analysis of the causes of such an apparently gross error, it is concluded that the main source of pitfalls arises from neglecting those typical clinical features differentiating prolapsed disk from oncogenetic sciatica. When oncogenetic sciatica is suspected Computed Tomography is inappropriate and even misleading, while the elective investigation is Magnetic Resonance. PMID- 7782866 TI - Intramedullary spinal neurinoma: case report and review of 46 cases. AB - A case of intramedullary neurinoma of the cervical spinal cord in a patient with no sign of von Recklinghausen's disease is reported. This case was diagnosed by computed tomography and magnetic resonance imaging and treated surgically. The literature covering 46 other cases is reviewed. The discussion, examines the possible etiology, the role of diagnostic procedures and the difficulties of the surgical treatment of these tumors. PMID- 7782867 TI - Intramedullary spinal cord metastasis. Case report. AB - The authors report a case of intramedullary spinal cord tumor in a 52-years old woman operated, 5 years before the beginning of medullary syndrome, for mammary carcinoma. Intramedullary metastasis was associated to another secondary localization in the pituitary stalk. The importance of magnetic resonance image and aggressive treatment is stressed. PMID- 7782868 TI - Spontaneous spinal subdural hematoma. AB - A case of spontaneous spinal subdural hematoma is reported. Clinical signs at onset, laboratory investigations and bloody CSF at lumbar punction were suggesting of subarachnoid hemorrhage. MRI was fully diagnostic. Surgery was ruled out and spinal compression cleared spontaneously over one week. Etiological factors, possible diagnostic pittfalls and the indication surgical decompression are discussed. PMID- 7782869 TI - Helping our international colleagues. PMID- 7782870 TI - Motivational orientations of urban- and rural-based RNs: implications for staff development educators. AB - Part of professional development is influencing RNs to return for an undergraduate degree, a challenge for the staff development educator. Expanding on earlier research using Boshier's Educational Participation Scale to reveal motivational orientations, the authors queried 5 groups of RNs who were enrolled in BSN education between 1990 and 1992 (N = 235) and living in rural and urban areas of Texas. There were no significant differences of overall motivational orientations, yet RN students living in rural areas scored higher in professional knowledge (P = 0.03) whereas urban-based RN students scored higher in compliance with authority (P = 0.02). Specific marketing and educational strategies are discussed. PMID- 7782871 TI - A collaborative model for research development and utilization: process, structure, and outcomes. AB - Nursing research development has long been viewed by practicing nurses as an activity for those in academia with the "thinking time" and resources to support scientific investigation. This view is being challenged by nurses in one hospital and its affiliated university. They are setting the pace for research activities by establishing a consortium to enhance collaborative research development and utilization. The author describes the model and how its goals have been operationalized through establishing an innovative collaborative structure. Suggestions for implementing such programs are described. Programmatic outcomes achieved in the first 3 years are also described. PMID- 7782872 TI - The impact of teacher characteristics on teaching. AB - A great deal has been written about the impact of positive characteristics on success in teaching. But what of negative characteristics? How might these have an impact on teaching? This question is explored in this article. The answer to this question can help staff development and inservice educators increase awareness of the hidden influences on teaching. PMID- 7782874 TI - Implementing the Performance Based Development System (PBDS) at Naval Medical Center San Diego. AB - Competency-based performance development is an educational tool that assesses the knowledge and skill base of an RN to enable staff development personnel to formulate orientation and training specific to that individual's learning needs. Theoretically, competency-based performance development is a time-efficient method for orientation. Recent healthcare reform, budgetary constraints, and downsizing have also affected the military. The stimulus, rationale, and obstacles experienced in implementation of this program in the military are common to all staff development educators. PMID- 7782873 TI - Professional autonomy: a pilot study to determine the effects of a professional development program on nurses' attitudes. AB - In this article, the authors describe a pilot study conducted to evaluate a component of a professional development program designed for Clinical Nurses in a general teaching hospital. Permission was obtained to use an established instrument for measuring attitude toward professional autonomy. A non equivalent pre-test/post-test, control group design was used. Results indicate that the program was influential in changing nurses' attitudes toward autonomy. Implications of using an instrument designed for an American cohort of nurses and modified to depict an Australian nursing culture are discussed. PMID- 7782875 TI - The preceptor experience: a qualitative study of perceptions of nurse preceptors regarding the preceptor role. AB - This qualitative, exploratory, and descriptive survey was undertaken to identify benefits and disadvantages of the preceptor role as perceived by nurse preceptors. Information regarding rewards preceptors perceived as desirable also was obtained. Findings from this study can be used to develop preceptor programs that increase job satisfaction for preceptors and improve the learning environment for orientees. PMID- 7782876 TI - How to develop a staff development indicator. AB - In this article, the author describes a step-by-step approach to generating staff development indicators, as well as examples of the evolving indicator during the development process. Quality improvement indicators are necessary, not only for patient care activities, but also for service activities related to patient care. Staff development is one such service. PMID- 7782878 TI - The impact of computer anxiety and computer resistance on the use of computer technology by nurses. PMID- 7782879 TI - Who teaches the teachers? PMID- 7782880 TI - Rapid, high-stakes decisions amid frantic innovation. PMID- 7782877 TI - The role of staff development in creating a research-based practice environment. PMID- 7782882 TI - Senior nursing students' self-reported college experiences and gains toward liberal education goals. AB - The purpose of this descriptive study is to assess baccalaureate nursing students' self-reported achievements toward liberal education goals in college and university settings and compare them to norms for the general college population by measuring their perceived involvement in campus life and activities. At the end of the spring semester, senior nursing students from 11 nursing programs in the Midwest filled out the College Student Experience Questionnaire, developed by Pace (1984), which measures the effort students put into liberal education goals. Nursing students reported high involvement in academic activities, but little involvement in other types of experiences in the college; they reported significant progress toward academic goals like intellectual skills, but less progress toward liberal education goals like art, literature, and music. Nursing students were very similar to other college students (except for students in selective liberal arts colleges) in reported involvement in activities and made similar progress toward liberal education goals. PMID- 7782881 TI - Knowledge-driven problem-solving models in nursing education. AB - This paper compares the hypothetico-deductive model of clinical problem solving commonly used in current nurse education and practice with the knowledge-driven problem-solving model (Bordage, Grant, & Marsden, 1990). It is argued that the knowledge-driven model provides a more complete account of the processes involved in clinical problem solving. The knowledge-driven model emphasizes the organization and availability of relevant content knowledge stored in memory as the prime determinant of clinical problem solving. This contention is discussed in relation to the development of a clinical problem-solving task for nursing students and its implications for nursing curricula. PMID- 7782883 TI - International nurses' experiences seeking graduate education in the United States. AB - Nurses from many countries in the world continue to seek further education in the U.S. every year. This study examined their experiences (N = 83) and those of the host institutions (N = 35) in the U.S. regarding the difficulties each experienced in coping with unfamiliar curricula and cultural mores, as well as financial constraints. PMID- 7782884 TI - Reflective practice: a focus for caring. AB - Nurse education has long been plagued by a perceived disjuncture between theory and practice. This paper explores the use of reflection as a mechanism to enable students of nursing to overcome this problem. A grounded theory approach is used to study a group of first-year students undertaking a 3-year undergraduate nursing course. Results of the study indicate that the use of the reflective processes of clinical debriefing and journaling does impact on the environment, the process, and the focus of learning. Anxiety associated with the learning environment was reduced through peer support and cooperation. In addition, students moved from a passive to a more active mode of learning. The most significant finding was that, over time, reflective processes resulted in the emergence of the client as the central focus of care. PMID- 7782885 TI - Scholarly productivity levels of nursing faculty in a geriatrics education program. PMID- 7782887 TI - Professional role development in baccalaureate nursing education. PMID- 7782886 TI - Effect of an HIV/AIDS elective on nursing students' knowledge and comfort levels in providing care to PWAs. PMID- 7782889 TI - Development of an essential health pattern assessment tool for associate degree nursing students. PMID- 7782888 TI - Professional Nursing Student Retention Program. PMID- 7782890 TI - Teaching cultural sensitivity. PMID- 7782891 TI - Study groups among nursing students. PMID- 7782892 TI - Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. AB - Because the human gut microbiota can play a major role in host health, there is currently some interest in the manipulation of the composition of the gut flora towards a potentially more remedial community. Attempts have been made to increase bacterial groups such as Bifidobacterium and Lactobacillus that are perceived as exerting health-promoting properties. Probiotics, defined as microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, have been used to change the composition of colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. Nondigestible oligosaccharides in general, and fructooligosaccharides in particular, are prebiotics. They have been shown to stimulate the growth of endogenous bifidobacteria, which, after a short feeding period, become predominant in human feces. Moreover, these prebiotics modulate lipid metabolism, most likely via fermentation products. By combining the rationale of pro- and prebiotics, the concept of synbiotics is proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for classification as health-enhancing functional food ingredients. PMID- 7782893 TI - Dietary nucleotides accelerate intestinal recovery after food deprivation in old rats. AB - Previous studies in very young rats have shown that dietary nucleotides improve small intestine repair after injury or malnutrition. To investigate the potential effect of nucleotides in old rats, which have a diminished capability for intestinal repair, 17-mo-old rats were deprived of food for 5 d and then fed a nucleotide-free diet or a nucleotide-supplemented diet for 3 or 6 d. Intestinal jejunal and ileal mucosal weight, protein and DNA were evaluated as intestinal growth markers, and brush-border maltase, sucrase, lactase and aminopeptidase activities were evaluated as intestinal differentiation markers. The adenine nucleotide pool and the adenylate energy charge were also evaluated as indices of nucleotide availability. Food deprivation significantly decreased mucosal growth markers as well as differentiation markers in both jejunum and ileum. The ATP pool was also significantly depressed, but the adenylate energy charge was not significantly altered. To a certain extent, refeeding restored the losses, but in the rats that were fed the nucleotide-free diet, the restoration of the jejunum was significantly slower and the restoration of the ileum differentiation markers was incomplete compared with the rats fed the nucleotide-supplemented diet. The results suggest that dietary nucleotide intake in the elderly may accelerate the normal physiological intestinal response to refeeding after food deprivation. PMID- 7782894 TI - Deficiency of vitamin E and selenium enhances calcium-independent phospholipase A2 activity in rat lung and liver. AB - Conditions promoting oxidative stress, which is implicated in many diseases, activate phospholipases A2, a family of enzymes central to phospholipid metabolism and signal transduction. Little is known about isozyme specificity with respect to this activation process. Accordingly, a dietary deficiency model known to induce oxidative stress was used to investigate phospholipase A2 isozyme activity in rat tissues. Long-Evans hooded rats were fed purified diets for 6 wk with or without the addition of vitamin E and selenium in a 2 x 2 factorial design. Phospholipase A2 activity was assessed in lung, liver, kidney and heart cytosol and microsomes in the presence (5 mmol/L CaCl2) or absence (5 mmol/L EGTA) of calcium with dipalmitoylphosphatidylcholine at pH 6.5. Lung phospholipase A2 activity was also assessed with 1-stearoyl-2 arachidonoylphosphatidylcholine as substrate at pH 8.5. Organ samples from rats deficient in both nutrients showed two- to tenfold higher calcium-independent phospholipase A2 activity in lung cytosol and microsomes, and in liver cytosol compared with samples from control and single nutrient-deficient rats. In contrast, the calcium-dependent activity was affected only slightly. The malondialdehyde concentration of the organs was measured and the pattern obtained mirrored that of enhanced phospholipase A2 activity for lung but not for liver. The enhanced phospholipase A2 activity in the lung cytosol and microsomes from rats deficient in both nutrients was partially blocked by p-bromophenacylbromide, further enhanced by dithiothreitol and unaffected by treatment with diisopropylfluorophosphate. These results suggest that deficiency of both vitamin E and selenium activates and/or induces unique calcium-independent forms of phospholipase A2 markedly in rat lung, and to a lesser extent in liver. PMID- 7782895 TI - Amylopectin starch promotes the development of insulin resistance in rats. AB - Starches that are high in amylopectin are digested and absorbed more quickly than starches with a high amylose content and produce larger postprandial glucose and insulin responses. The aim of this study was to test the hypothesis that feeding rats a diet containing quickly digested starch could promote insulin resistance. Sprague-Dawley rats were fed either a high amylopectin or high amylose diet (two 10-g meals per day), and insulin sensitivity was assessed after 9 wk by intravenous glucose tolerance test (IVGTT). In the rats fed the high amylopectin diet, glucose tolerance was significantly lower (P < 0.05) and the insulin response to IVGTT was twice as high as in rats fed the high amylose diet (P < 0.05). A second study using Wistar rats investigated the time course of these changes. Differences in the insulin response to the IVGTT were not evident at 4 wk but began to emerge at 8 wk, and by 12 wk the insulin response was 100% greater in rats fed the high amylopectin diet (P < 0.05) than in those fed the high amylose diet. In addition, basal plasma insulin concentration was higher in rats fed the high amylopectin diet (P < 0.05). There were no differences, however, in glucose tolerance at any time point. The results suggests that quickly digested starch promotes the development of insulin resistance in rats. The relatively slow time course resembles the normal development of insulin resistance in humans. PMID- 7782896 TI - Glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase are differentially regulated in rats by dietary selenium. AB - Phospholipid hydroperoxide glutathione peroxidase (PHGPX) and classical glutathione peroxidase (GPX1) are encoded by separate genes with only about 40% amino acid and nucleic acid sequence identity. To determine the response of tissue PHGPX expression to dietary Se level and to compare these responses with those for GPX1, weanling male rats were fed amino acid diets containing from 2 ( Se) to 130 (+Se) microgram Se/kg diet or a torula diet containing 5 and 190 micrograms Se/kg diet as Na2SeO3 for 28 d. Tissues were analyzed for PHGPX and GPX1 activity and mRNA. There was no effect of Se on growth. In -Se rats, GPX1 activity was reduced to 1% in liver and 4-9% in heart, kidney and lung compared with +Se rats; PHGPX activity was reduced only to 25-50% in these four tissues. The Se response curves indicated that the dietary Se requirement to reach plateau liver PHGPX activity was half that required for plateau GPX activity. In -Se rats, liver and heart GPX1 mRNA levels were reduced to 6 and 12%, respectively, whereas PHGPX mRNA was not significantly affected by Se deficiency. Notably, 65 micrograms Se/kg diet resulted in plateau liver GPX1 mRNA levels but not plateau GPX activity. Testis had the lowest GPX activity and GPX1 mRNA of all tissues examined, but had 15-fold higher PHGPX activity and 45-fold higher PHGPX mRNA levels when compared with liver. There was no significant effect of dietary Se on testis GPX1 and PHGPX mRNA levels. This study demonstrates that these two selenoperoxidases are differentially regulated by dietary Se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782897 TI - Copper deficiency alters rat peptidylglycine alpha-amidating monooxygenase activity. AB - Perinatal copper deficiency was studied in 1-mo-old female and male Sprague Dawley rat offspring to investigate changes in cuproenzymes. Offspring of dams given the low Cu treatment beginning at d 7 of gestation exhibited signs characteristic of Cu deficiency, including a 90% reduction in liver Cu levels compared with Cu-adequate controls. Compared with Cu-adequate rats, Cu-deficient rats had lower activities of the cuproenzymes peptidylglycine alpha-amidating monooxygenase (PAM), cytochrome c oxidase (CCO), and Cu,Zn-superoxide dismutase (SOD) in heart and midbrain samples. Activity of dopamine-beta-monooxygenase (DBM) was higher in midbrain and lower in heart samples from Cu-deficient compared with Cu-adequate rats. Following 1 mo of Cu repletion, PAM and CCO activity were still lower in heart of Cu-replete rats. Midbrain DBM activity was still elevated in the former Cu-deficient males. A second study was conducted using weanling male Holtzman rats. After 5.5 wk of treatment, Cu-deficient rats had signs characteristic of Cu deficiency and lower PAM, CCO and DBM activities in heart but not midbrain as compared with Cu-adequate rats. The PAM activity was lower following Cu deficiency. Perhaps neuropeptide maturation is compromised by Cu deficiency. PMID- 7782898 TI - Large supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats. AB - Poly(ADP-ribose) is a homopolymer of ADP-ribose units synthesized from NAD+ on nuclear acceptor proteins and is known to be involved in DNA repair. It is not known whether large oral doses of the clinically utilized NAD precursors nicotinic acid or nicotinamide affect poly(ADP-ribose) metabolism or the cellular response to DNA damage. In our first study, using Fischer-344 rats, 2 wk of dietary nicotinic acid supplementation (500 and 1000 mg/kg diet) caused elevated levels of NAD+ in the blood, liver, heart and kidney, while nicotinamide caused elevated levels only in the blood and liver, compared with controls fed a diet containing 30 mg/kg nicotinic acid. Both nicotinic acid and nicotinamide, at 1000 mg/kg diet, caused elevations in liver NAD+, by 44 and 43%, respectively. Only nicotinamide, however, elevated liver poly(ADP-ribose) (63% higher than control group). Following treatment with the hepatocarcinogen diethylnitrosamine, higher levels of hepatic NAD+ were observed in rats fed both nicotinic acid and nicotinamide at 1000 mg/kg diet, but only nicotinic acid supplementation caused a greater accumulation of hepatic poly(ADP-ribose) (61% higher than control group). Neither of the dietary treatments significantly affected the proportion of the liver occupied by placental glutathione-S-transferase positive foci. These results show that poly(ADP-ribose) synthesis is not directly responsive to hepatic NAD+ levels during niacin supplementation, and that the mechanisms of action of nicotinic acid and nicotinamide are different. The observed changes in poly(ADP-ribose) metabolism do not appear to cause any change in susceptibility to chemically induced carcinogenesis in this organ. PMID- 7782899 TI - Protein-deficient pigs cannot maintain reduced glutathione homeostasis when subjected to the stress of inflammation. AB - The mechanisms responsible for depletion of systemic glutathione levels in nutritional deprivation and/or in infective and inflammatory conditions have not been fully established. We quantified the effects of protein undernutrition and experimental inflammation on the concentration and synthesis of reduced glutathione in the erythrocytes, liver and jejunal mucosa of young pigs. Two groups of five piglets consumed diets containing either 23 or 3% protein and, after 4 wk, were infused intravenously with [13C2]glycine before and 48 h after subcutaneous injections of turpentine. Erythrocyte, hepatic and intestinal mucosal reduced glutathione was quantified as the monobromobimane derivative by HPLC. Reduced glutathione synthesis was determined by measurements of the tracer/tracee ratio of reduced glutathione-bound glycine. In well-nourished piglets, turpentine injection had no effect on erythrocyte reduced glutathione concentrations or rate of synthesis. Protein undernutrition was associated with lower erythrocyte reduced glutathione concentrations (1.05 +/- 0.04 vs. 1.32 +/- 0.06 mmol/L, P < 0.01) and synthesis (42 +/- 5 vs. 60 +/- 5%/d), and turpentine inflammation caused a further fall in erythrocyte reduced glutathione concentration to 0.96 +/- 0.05 mmol/L, despite a significant (P < 0.05) increase in reduced glutathione synthesis. The combination of protein undernutrition and inflammation had a marked effect on mucosal reduced glutathione concentration (37 +/- 3% of control) and synthesis (65 +/- 5% of control). Hepatic reduced glutathione concentration and synthesis did not differ in the two groups. We conclude that the biosynthetic supply of reduced glutathione is sufficient to withstand an inflammatory challenge in well-nourished piglets but not in protein deficient animals. PMID- 7782900 TI - A brief, telephone-administered food frequency questionnaire can be useful for surveillance of dietary fat intakes. AB - A 13-item questionnaire designed for quick telephone administration was evaluated for use in surveillance of fat intake in the United States. Study populations included 560 middle-aged and older adults from Beaver Dam, WI, 252 middle-aged and older women from Wisconsin, 73 young, low income Hispanic women from Chicago, IL, 52 older adults from Arizona and 135 younger adults from Augusta, GA. Correlations between fat scores and fat intakes measured by multiple food records or recalls or by more extensive food frequency questionnaires ranged from 0.33 to 0.60, similar to results from other published questionnaire validation studies. Correlations with percentage of energy from fat were lower (0.26 to 0.42), except for the Chicago population, for which there was no correlation (-0.02). There was no systematic variation in correlations among other subgroups defined by demographic and health-related characteristics, including race (black vs. white). Most, but not all, of the substantial differences in fat intakes among subgroups were identified by the questionnaire. The questionnaire will not capture small differences in intakes among groups and is inappropriate when the sample size is limited or for populations with diets substantially different from the typical U.S. diets, such as the Chicago population. However, with attention to its limitations, the questionnaire is useful for surveillance. PMID- 7782901 TI - Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. AB - Studies on the effect of phosphatidylcholine administration on memory are limited. We administered egg phosphatidylcholine to mice with dementia and to normal mice and compared the differences in memory and serum choline concentration, and choline and acetylcholine concentrations and choline acetyltransferase activities of three forebrain regions (cortex, hippocampus and the remaining forebrain). Mice with dementia were produced by mating sibling mice who had impaired memory for > 20 generations. These mice had poor memory and low brain acetylcholine concentration. We administered 100 mg of egg phosphatidylcholine (phosphatidylcholine group) or water (control group) by gavage to each mouse daily for about 45 d. Control mice with dementia had poorer memory in passive avoidance performance and lower brain choline (cortex and hippocampus) and acetylcholine (hippocampus and forebrain excluding cortex and hippocampus) concentrations and lower cortex choline acetyltransferase activity than the control normal mice (P < 0.05). The administration of phosphatidylcholine to mice with dementia improved memory and generally increased brain choline and acetylcholine concentrations to or above the levels of the control normal mice. In normal mice, phosphatidylcholine treatment did not affect memory or acetylcholine concentrations in spite of the great increase in choline concentrations in the three brain regions. Serum choline concentration in mice treated with phosphatidylcholine increased to a similar level in both strains of mice, indicating that the absorption of phosphatidylcholine was not impaired in mice with dementia. The results suggest that administration of egg phosphatidylcholine to mice with dementia increases brain acetylcholine concentration and improves memory. PMID- 7782902 TI - Primary chylomicronemia in patients with severe familial hypertriglyceridemia responds to long-term treatment with (n-3) fatty acids. AB - Because it disturbs microcirculation, chylomicronemia can cause severe clinical complications such as acute pancreatitis. Dietary measures are very important in the prevention and treatment of this condition. Dietary supplementation with (n 3) fatty acids has been shown to be of benefit in short-term treatment of chylomicronemia. To evaluate the long-term efficacy of (n-3) fatty acids we added 2.16 or 4.32 g/d (for 3 mo) and 3.24 g/d (for a further 8 mo after 1 mo of no treatment) (n-3) fatty acids to the diet of eight patients with primary chylomicronemia. Serum triglycerides decreased significantly from 15.0 +/- 2.5 to 9.9 +/- 2.8 mmol/L (P < 0.01) after 11 mo of treatment, and VLDL triglycerides decreased from 12.3 +/- 2.8 to 9.0 +/- 2.4 mmol/L (P < 0.01), resulting in a significant decrease of plasma viscosity from 1.56 +/- 0.17 mPa-s to 1.47 +/- 0.12 mPa.s (P < 0.01). Total cholesterol, HDL and LDL cholesterol as well as lipoprotein (a) and fibrinogen concentrations were not affected by fish oil treatment. The presence of chylomicrons and chylomicron remnants (apolipoprotein B 48 concentration in the lipoprotein fraction with a density lower than 1.006 kg/L) was significantly reduced from 4.82 +/- 1.08 to 1.06 +/- 0.38 mg/L (P < 0.01). Body weight increased significantly from 71.0 +/- 4.6 kg to 75.2 +/- 5.3 kg after 11 mo of treatment with (n-3) fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782903 TI - In vivo methylation capacity is not impaired in healthy men during short-term dietary folate and methyl group restriction. AB - Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on in vivo methylation capability. The men were housed in a metabolic unit for the entire 108 d of the study. After a 9-d baseline period (Period 1), the men were fed a soy-product-amino acid defined diet for 45 d, which provided 25 micrograms/d of folate for 30 d (Period 2) and, with a folate supplement, 99 micrograms/d for 15 d (Period 3). During Period 2 and Period 3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (Periods 4-6), with a crossover of methionine intakes in Period 5 and Period 6. A 1-g oral dose of nicotinamide was given at the end of each period and methylated urine metabolites determined. Other measures related to in vivo methylation capability included urine creatinine, and plasma and urine carnitine. Even with moderate folate depletion, none of these measures was decreased by low methionine and choline intakes. Plasma methionine concentrations were unchanged throughout. Limiting exogenous methyl group intake by restricting dietary methionine and choline did not impair in vivo methylation capabilities for the variables tested, even at low folate intake. PMID- 7782904 TI - Sourdough fermentation or addition of organic acids or corresponding salts to bread improves nutritional properties of starch in healthy humans. AB - Postprandial blood glucose and insulin responses to barley bread containing organic acids or corresponding salts were evaluated in healthy human subjects. The satiety score and the rate and extent of in vitro starch digestion were also studied. Lactic acid was generated by use of a homofermentative starter culture or added to the dough. In addition, products were baked with Ca-lactate, or with Na-propionate at two different concentrations. Consumption of the product baked with a high concentration of Na-propionate significantly lowered the postprandial blood glucose and insulin responses, and significantly prolonged the duration of satiety compared with all other breads. When subjects consumed the breads baked with sourdough, lactic acid and Na-propionate, their glucose and insulin responses were reduced compared with the wholemeal bread alone. The rate of in vitro amylolysis was reduced only by ingestion of the breads containing lactic acid, suggesting that the beneficial impact of Na-propionate on metabolic responses and satiety was related to effects other than a reduced rate of starch hydrolysis. All bread products had a similar concentration of in vitro resistant starch of 1.3-2.1 g/100 g (starch basis). It is concluded that sourdough baking and other fermentation processes may improve the nutritional features of starch. The results also demonstrate that certain salts of organic acids may have metabolic effects. PMID- 7782905 TI - Estimation of rat body composition by means of electromagnetic scanning is altered by duration of anesthesia. AB - We determined the effect of anesthesia on estimation of fat-free mass and body fat in rats using electromagnetic scanning (EMS). Male Wistar Furth rats (n = 7, approximately 226 g) were injected with 66 mg/kg ketamine hydrochloride and 6.6 mg/kg xylazine intramuscular anesthesia. EMS measures were repeated every 4 min, up to 80 min post-anesthesia injection. From 4 to 44 min post-injection, the EMS signal and consequently the estimation of fat-free mass decreased from 198 +/- 5 to 180 +/- 5 g (mean +/- SD, P < 0.05). Conversely, the estimation of body fat increased by 63% during this period of anesthesia (12.9 +/- 2.9 vs. 21.1 +/- 2.6 g/100 g body wt, P < 0.05). In cohort animals (n = 6), body temperature and respiration rate declined following anesthesia (P < 0.05), and may have correspondingly suppressed EMS signal via reduced ion flux and/or muscular activity. In another study the effects of food deprivation, tail position, and anesthesia duration were demonstrated to alter estimation of fat-free mass (P = 0.0001), but these effects were not interactive (P > 0.05). Proximate analysis of body composition in cohort rats indicated that EMS predicted fat-free mass with a 3.5% error when estimated at 4 min post-anesthesia injection. Taken together, these data suggest that standardized EMS protocols should be adopted to account for effects of anesthesia, animal position and food deprivation. When manufacturer's equations are used, body composition should be measured immediately after induction of anesthesia. However, laboratories that choose to internally generate EMS regression equations with proximate analysis should determine and utilize the period of minimal variability in EMS measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782906 TI - Dietary fibers differ in their effects on large bowel epithelial proliferation and fecal fermentation-dependent events in rats. AB - The effects of different fiber types and processing on putative protective mechanisms for colorectal cancer were evaluated. Rats were fed diets of similar nutrient balance containing either no added fiber or 10% fiber from various sources. The rate of distal colonic epithelial proliferation, measured by the metaphase arrest method, was dependent on fiber type; ranking of fibers from highest to lowest yielded the following order: methylcellulose > coarse wheat bran > fine wheat bran approximately parboiled and extruded rice brans > no fiber (P = 0.012). Effect on stool output ranked identically. Ranking of effect on fecal pH, from most to least acidic was as follows: coarse wheat bran approximately the rice brans > fine wheat bran > no fiber approximately methylcellulose (P = 0.00001). Coarse wheat bran gave significantly higher fecal butyrate concentrations than did the rice brans, which in turn gave higher levels than fine wheat bran, methylcellulose and the no-fiber diet. Proximal colon epithelial proliferation was unaffected by diet although cecal short-chain fatty acid concentrations and pH were affected. Different fibers have different effects on events in the fecal environment and distal colonic epithelium. Putative protective events (increased output, low fecal pH, high butyrate, low proliferation) are not equally affected and are unlikely in themselves to allow prediction of the protective effect of a fiber. PMID- 7782907 TI - Brain iron, transferrin and ferritin concentrations are altered in developing iron-deficient rats. AB - To study the iron, transferrin, and ferritin distribution at subcellular levels in response to acute dietary iron deficiency, we tested the hypothesis that early post-weaning iron deficiency can change iron and iron regulatory protein concentrations in rat brain. Male Sprague-Dawley rats were fed diets containing either 2 or 35 micrograms iron/g for 2, 3 or 4 wk starting at 21 d of age. Brain iron, transferrin and ferritin concentrations in cytosolic and microsomal fractions of either whole brain or pons and cerebellum were then determined. After 14 d of dietary iron restriction, brain iron concentrations were 50% lower in the microsomal fraction and 30% lower in cytosol compared with controls. Brain cytosolic transferrin concentration almost doubled in the same animals. Brain ferritin concentration in fractions from rats fed the iron-deficient diet for 14 d was lower than in controls, but then remained fairly constant. Absolute brain weight and total brain protein contents were unaffected by iron restriction. This study extends previous research by demonstrating that the brain responds to changes in body iron status with a change in transferrin concentration. If the dietary restriction is quite severe, this adaptation is insufficient. This study also notes that brain ferritin decreases with decreasing body iron status, though it was less responsive than nonheme iron in liver. The concept that iron enters the brain through a highly regulated endocytotic process at the blood brain barrier, that undoubtedly involves the regulation of transferrin receptors in capillary endothelial cell, is supported by our observation of elevated transferrin concentrations in brain of iron-deficient rats. PMID- 7782908 TI - Corn oil, palm oil and butterfat fractions affect postprandial lipemia and lipoprotein lipase in meal-fed rats. AB - Our objective was to investigate the time course of postprandial lipemia and lipolytic activity in male Sprague-Dawley rats trained to eat meals containing butterfat fractions, palm oil or corn oil. Baseline and postprandial blood samples were obtained via a carotid cannula in rats fed the experimental diets for 4 wk. Rats fed saturated fats compared with corn oil showed a significantly greater peak increase in postprandial triacylglycerol concentrations. Corn oil ingestion resulted in significantly lower concentrations of cholesterol and triacylglycerol in plasma and significantly less triacylglycerol accumulation (millimoles per liter per 24 h) compared with ingestion of saturated fats. Postheparin plasma lipoprotein lipase activity and plasma insulin concentration were generally greater with ingestion of corn oil compared with palm oil or butterfat. Palm oil ingestion resulted in a biphasic plasma triacylglycerol response curve and greater postheparin plasma lipoprotein lipase activity compared with butterfat ingestion, suggesting differential effects of saturated fats on postprandial lipemia. Our results indicate that greater postprandial lipemia with ingestion of saturated fats compared with corn oil may be due in part to slower plasma triacylglycerol clearance. PMID- 7782909 TI - Muscle respiration in rats is influenced by the type and level of dietary fat. AB - Experiments were conducted to elucidate the role of muscle in the enhanced thermogenic response found in rats fed diets enriched with polyunsaturated fatty acids. Isolated soleus muscle respiration and plasma cholesterol and triglyceride concentrations were determined in rats (approximately 128 g wt, 5 wk age) fed diets (minimum 3 wk) containing coconut oil, beef tallow or safflower oil at 20, 40 or 60% of the total dietary energy in a 3 x 3 factorial design (5-6 rats per treatment). Diet type did not affect plasma cholesterol concentrations but plasma triglycerides were lower (P < 0.01) in rats fed safflower oil-based diets. Greater levels of fat in the diet resulted in higher (P < 0.01) plasma cholesterol concentrations and lower (P < 0.01) plasma triglyceride concentrations. Rats fed coconut oil had lower (P < 0.05) rats of soleus muscle respiration compared with rats fed the other two diets. This lower respiration rate was not related to changes in protein synthesis (cycloheximide-sensitive respiration). However, this change may partially be related to enhanced Na+,K+ transport (ouabain-sensitive respiration). The results indicate that muscle is partially responsible for the enhanced thermogenic response found in rats fed diets enriched with polyunsaturated fatty acids and that enhanced ion transport contributes to this response in muscle. PMID- 7782910 TI - Inhibition of starch digestion by alpha-amylase inhibitor reduces the efficiency of utilization of dietary proteins and lipids and retards the growth of rats. AB - Digestion/absorption and nutritional utilization of starch, protein and lipids were studied in rats fed diets containing purified kidney bean alpha-amylase inhibitor at levels of 0, 1.6, 3.3 and 6.6 g/kg diet. At the two higher levels, the growth rate of rats and the apparent digestibilities and utilization of dietary starch and protein were significantly less than in control rats, and losses of nitrogen, lipids and carbohydrate resulted in a significant reduction in dry body weight. Some organs of the body were also affected: the relative dry weights of the intestines and the pancreas were higher, whereas liver and thymus weights were lower than in control rats. As starch digestion in the small intestine was negligible at higher inhibitor concentrations, the cecum was practically blocked by solidified digesta. This effect and the ensuing bacterial fermentation stimulated the growth of this tissue by hyperplasia and hypertrophy. However, as the distension was not always sufficient, the organ was occasionally ruptured and the rats had to be killed. Inhibitor doses in this work were comparable to those in clinical studies, implying that the use of the inhibitor is not without health risks. Moreover, diets rich in alpha-amylase inhibitor such as those containing transgenic plants with high levels of inhibitor gene expression cannot be recommended in intensive animal production. PMID- 7782911 TI - Petroselinic acid from dietary triacylglycerols reduces the concentration of arachidonic acid in tissue lipids of rats. AB - Studies in vitro have revealed that triacylglycerols containing petroselinoyl [18:1(n-12)] moieties are hydrolyzed by pancreatic lipase at much lower rates than other triacylglycerols. To assess the lipolysis and absorption in vivo of such unusual triacylglycerols, diets containing 120 g seed oil triacylglycerols of coriander (Coriandrum sativum) per kg diet at a level of 72 g 18:1(n-12) moieties/100 g oil were fed to a group of weaned male Wistar rats without restriction for a period of 10 wk. For comparison, groups of rats were fed similar isocaloric diets containing plant oil triacylglycerols with various levels of oleoyl [18:1(n-9)] moieties, e.g., high oleic sunflower seed oil [75 g 18:1(n-9)/100 g oil], olive oil [(66 g 18:1(n-9)/100 g oil], medium oleic rapeseed oil [54 g 18:1(n-9)/100 g oil] and conventional high linoleic sunflower seed oil [25 g 18:1(n-9)/100 g oil]. All diets were supplemented with 20 g corn oil/kg diet. Consumption of coriander oil, compared with the other oils, led to significantly greater liver weights. No significant differences were observed among the groups fed various levels of oleic acid in body weight, the weights of heart, liver, kidneys, spleen or testes, lipid content of heart, or total cholesterol, HDL cholesterol and triacylglycerol concentrations of blood plasma. Ingestion of coriander oil led to incorporation of 18:1(n-12) into heart, liver and blood lipids and to a significant reduction in the concentration of arachidonic acid in the lipids of heart, liver and blood with a concomitant increase in the concentration of linoleic acid compared with results for the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782912 TI - Comparative absorption and transport of five common carotenoids in preruminant calves. AB - Preruminant calves, maintained in a monogastric state by feeding an all-liquid diet, were used to compare the serum appearance and lipoprotein transport of five different carotenoids over 144 h. Thirty newborn calves were fed milk replacer for 1 wk and then randomly assigned to six groups (n = 5), with each group receiving a single 20-mg oral dose of beta-carotene in water-soluble beadlets, canthaxanthin in water-soluble beadlets, lutein in oil, lycopene in oil, crystalline alpha-carotene in oil or crystalline beta-carotene in oil as part of a morning meal. Serial blood samples were taken by jugular puncture for up to 1 wk post-dosing. Lipoprotein separation and analysis were completed with selected animals. All carotenoids were absorbed, but in variable amounts. At peak serum carotenoids levels, HDL contained 70-90% of the carotenoids. Canthaxanthin and lutein peaked earlier in serum (8 and 12 h) than did the less polar lycopene, alpha-carotene, and beta-carotene (16, 24 and 24 h). Canthaxanthin and lutein were also cleared more quickly from the serum. Serum concentrations of alpha carotene and lycopene displayed slower disappearance rates than did beta carotene. The peak serum level (nmol/L +/- SEM) of canthaxanthin (392 +/- 136) was lower than that of beta-carotene (1245 +/- 425), and carotenoids levels of calves receiving these commercial beadlet sources were higher than the serum levels of calves receiving beta-carotene (45 +/- 17.5), alpha-carotene (42 +/- 18.0), lutein (51 +/- 9.5) and lycopene (18 +/- 4.6), which were fed in oil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782913 TI - Aging and food restriction alter some indices of bone metabolism in male rhesus monkeys (Macaca mulatta). AB - Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long term (> 6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise normal skeleton. PMID- 7782915 TI - Maternal dietary carbohydrate restriction and mild-to-moderate exercise during pregnancy modify aspects of fetal development in rats. AB - To determine whether acute bouts of exercise during pregnancy would predispose the fetus to increased risk if maternal dietary carbohydrate were restricted, untrained pregnant rats were randomly assigned to a 0% (low), 12% (moderate) or 60% (high) glucose diet, and either rested or exercised daily for 20 min from d 16 to term on a rodent treadmill at a mild (15.5 m/min) or moderate (24.3 m/min) intensity. A 3 x 3 nested factorial model with and without food intake as a covariate was employed. Both greater exercise intensity and the lower levels of dietary carbohydrate independently decreased term maternal liver and plantaris glycogen concentrations and increased plasma lactate concentrations. However, significant differences due to exercise disappeared (except for plasma lactate) with food intake controlled for in the model, indicating that energy deficits modulated these exercise effects. In contrast, for the offspring, when food intake was controlled for, a restricted level of maternal dietary carbohydrate significantly lowered fetal weight, plasma glucose and insulin concentrations and liver glycogen concentrations measured at term. Exercise alone did not reduce mean fetal weight if nested weights within a litter were used in the statistical analysis. Mild to moderate maternal exercise lowered only fetal plasma glucose concentrations and only if maternal food intake was not controlled for. These results indicate that acute exercise during pregnancy can have detrimental effects on fetal development only if dietary glucose is severely restricted. Otherwise, adequate glucose and energy in the maternal diet in untrained pregnant rats during repeated bouts of acute exercise seem to protect the fetus. PMID- 7782914 TI - The validity of extrinsic stable isotopic labeling for mineral absorption studies in rats. AB - The use of extrinsic stable and radioisotopic labels (Fe, Zn, Cu and Se) was compared with the use of intrinsic labels by measuring label retention in rats. Saccharomyces cerevisiae (Hansen strain CBS 1171) was prepared intrinsically enriched with a stable isotope of iron, zinc, copper or selenium, and unenriched freeze-dried yeast was extrinsically labeled with the appropriate stable and/or radioisotope. Male Wistar rats, weighing 80-100 g and fed a purified diet, were given a test meal of one of the above labeled yeasts. Isotopic retention was determined by fecal monitoring. Retention of the stable isotopes was determined by thermal ionization quadruple mass spectrometry (TIQMS) and retention of the radioisotopes by counting feces in a whole-body counter. The results indicated that the behavior of the labels differed among the minerals, with copper as the only one in which the intrinsic and extrinsic stable isotopes were comparably retained. With zinc, retention of the extrinsic radiolabel and intrinsic label was similar, but retention of the extrinsic stable isotope label was higher. With iron, the intrinsic label had a significantly lower retention than the two extrinsic labels; with selenium, retention of all three labels was different, but these differences were not of a sufficient magnitude to conclude that extrinsic stable isotopic labelling is not valid. These results demonstrate that an extrinsic stable isotope label can be used for copper, selenium and inorganic iron, but that such a label is not valid for studies on zinc. PMID- 7782916 TI - Role of Nutrition in Lung Development and Function. Proceedings of a symposium. Anaheim, California, April 25, 1994. PMID- 7782917 TI - Role of vitamin A in lung development. AB - There is good rationale for presuming a role for vitamin A in lung development. In situ studies have demonstrated that certain retinoic acid (RA) receptor proteins are localized in a specific fashion during fetal lung branching and airway growth. Vitamin A stores are high in fetal lung and decrease toward term, possibly being utilized for changes in lung morphogenic remodeling. The binding activity, levels and expression of the cytosolic and nuclear receptor proteins for vitamin A undergo changes before and after birth in rat lung. RA slows fetal Type II cell proliferation in culture but stimulates choline incorporation into phosphatidylcholine. RA can regulate several other factors involved in lung development such as homeobox genes, matrix molecules and certain growth factors. Further study is needed on this potential functional role of RA in lung. Retinol deficiency results in lung histopathology that is similar to bronchopulmonary dysplasia, which occurs frequently in human premature neonates. Clinical trials are attempting to define the role of supplementation of vitamin A in the prevention and treatment of that condition. PMID- 7782918 TI - The developing rat lung fibroblast and alveolar type II cell actively recruit surfactant phospholipid substrate. AB - Timely, adequate production of pulmonary surfactant is critical for survival at birth. This process is dependent on both maternal nutrition and glucocorticoids. Fetal rat lung lipofibroblast triglyceride accumulation is saturable, temperature dependent and stimulated by glucocorticoids and cyclic AMP in primary cell culture. Spontaneous triglyceride uptake by fibroblasts increases ninefold between 17 and 21 days (= term) gestation and is stimulated 30-80% by exogenous glucocorticoid treatment. Coculture of Type II cells with fibroblasts preloaded with 3H-trioleate and increasing amounts of triglyceride results in a concomitant increase in saturated phosphatidylcholine (SPC) synthesized by Type II cells. Dexamethasone stimulates mobilization of fibroblast triglyceride incorporation into Type II cell-SPC by 36-40%. The hormonally regulated uptake and mobilization of triglyceride suggest active recruitment of surfactant phospholipid substrate by both alveolar connective tissue and epithelial cells. PMID- 7782919 TI - Role of fatty acids in lung development. AB - The role of maternal dietary fat in the regulation of fetal and newborn lung surfactant lipid synthesis has not been completely elucidated. Dietary fat can modulate cell membrane phospholipid fatty acid composition, resulting in altered membrane fluidity and affecting cellular functions, including binding to hormone receptors and the binding and activity of membrane-associated enzymes. Two examples are discussed that support the hypothesis that exogenous fatty acids modulate phospholipid synthesis in the lung. In the first example, long-chain unsaturated fatty acids were found to inhibit glucocorticoid receptor binding in L2 cells, suggesting that fatty acids may affect steroid responsiveness during different developmental stages of the lung. In the second example, a relationship was established between changes in membrane lipid composition during lung development and the activity of cholinephosphate cytidylyltransferase, the rate limiting enzyme in phosphatidylcholine synthesis. The effects demonstrated in these in vitro studies will need to be confirmed by dietary studies of pregnant animals. PMID- 7782920 TI - Do polyunsaturated fatty acids protect against oxidant-induced lung damage? AB - Little disagreement exists concerning the importance of early provision of lipid nutrition to very low birth weight (VLBW) infants in terms of growth and development. However, considerable controversy surrounds the relationship of lipid and protection against oxidant-induced lung damage in experimental situations and in the vulnerable premature infant. This article reviews the results of experimental and clinical studies on the protective effects of lipids against oxidant injury and chronic lung disease. PMID- 7782921 TI - Effect of diet on lung structure, connective tissue metabolism and gene expression. AB - Nutritional impairment can adversely affect the respiratory system. The structure of the lung is altered by severe calorie-protein restriction in rodents producing an emphysema-like lesion after several weeks of severe caloric restriction. Biochemical and morphological evidence suggests destruction of collagen and elastin in nutritional emphysema. Impaired lung growth may explain the biochemical changes in growing animals. Although the molecular basis of nutritional emphysema is not known, altered gene expression by nutrients affects several metabolic pathways, and examples of the effects of nutrients on gene expression are given. Nutritional emphysema in animals may be relevant to humans because malnutrition may accelerate the progression of the disease in patients with advanced emphysema. PMID- 7782922 TI - Oxidatively fragmented phospholipids as inflammatory mediators: the dark side of polyunsaturated lipids. AB - Phospholipids containing a polyunsaturated fatty acyl residue at the sn-2 position are common constituents of cellular membranes and lipoprotein particles. Just as free polyunsaturated fatty acids can be oxidized, derivatized, and fragmented, phospholipid acyl residues are also subject to similar oxidative attack. Oxidative modification and/or fragmentation of phosphatidylcholines generate potent inflammatory mediators that mimic the biologic action of platelet activating factor (PAF). The oxidatively fragmented phospholipids with PAF-like activity act via the receptor for PAF and mimic most of its biologic actions. Thus, oxidation either through inappropriate inflammatory processes, endogenous oxygen metabolism or uptake of peroxidized lipids from the diet can all lead to inappropriate and unregulated generation of potent inflammatory mediators. PMID- 7782923 TI - Suppression of mevalonate pathway activities by dietary isoprenoids: protective roles in cancer and cardiovascular disease. AB - Diet-cancer and diet-cardiovascular disease interrelationships may be explained by the mevalonate-suppressive action of isoprenoid end products of plant secondary metabolism. Assorted monoterpenes, sesquiterpenes, carotenoids and tocotrienols posttranscriptionally down regulate 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, a key activity in the sterologenic pathway. The modest decrease in cholesterol synthesis is associated with a concomitant lowering of low-density lipoprotein cholesterol. The reductase activity in tumor tissues differs from that of liver in being resistant to sterol feedback regulation. Tumor reductase activity retains sensitivity to posttranscriptional regulation. As a consequence, the isoprenoid-mediated suppression of mevalonate synthesis depletes tumor tissues of two intermediate products, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are incorporated posttranslationally into growth control-associated proteins. At 10-fold higher concentrations, monoterpenes inhibit the protein isoprenyl transferases that catalyze this incorporation. At levels of intake likely provided by a diet based on Food Pyramid guidelines, assorted isoprenoids decrease cardiovascular disease risk and suppress the growth of initiated cells. At pharmacological levels of intake, isoprenoids block the initiation phase of chemical carcinogenesis. Isoprenoids targeted to the inhibition of the isoprenylation of oncogenic forms of ras proteins may offer a novel approach to chemotherapy. Adjunctive isoprenoids might decrease the level of competitive inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A reductase required to manage hypercholesterolemia. PMID- 7782924 TI - Dietary modulation of epidermal protein kinase C: mediation by diacylglycerol. AB - Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular binding site of the phorbol ester tumor promoters, protein kinase C (PKC). High-fat diets increase the activity of PKC but have no impact on the steady-state protein levels. Energy restriction reduces the activity of PKC, presumably through reduction in the steady-state levels of particular isoenzymes (PKC alpha and PKC zeta). Phorbol-binding studies with epidermal cells from mice fed energy restricted diets indicated a reduction of phorbol-binding sites in these cells. Investigations into lipid metabolism showed that both dietary fat and energy restriction increased epidermal cell diacylglycerol (DAG). The increase in DAG in cells from energy-restricted mice may be due to increased turnover of phosphatidylinositol, as was evident in the reduced phosphatidylinositol-4 phosphate and phosphatidylinositol-4,5-biphosphate and elevated inositol biphosphate and inositol triphosphate in these cells. PMID- 7782925 TI - Role of dietary sphingolipids and inhibitors of sphingolipid metabolism in cancer and other diseases. AB - Sphingolipids are found in all eukaryotic and some prokaryotic organisms and participate in the regulation of cell growth, differentiation, and diverse cell functions including cell-cell communication, cell-substratum interactions and intracellular signal transduction. Nonetheless, the field of nutrition has given scant attention to these compounds so that little is known about the following fundamental questions: What is the fate of sphingolipids that are consumed in food? Does consumption of dietary sphingolipids affect the behavior of cells in the gastrointestinal tract or other organs? How do other factors in the diet affect sphingolipid metabolism? Several recent findings underscore the importance of these questions, for examples: 1) Sphingolipids are digested throughout the GI tract to ceramide and sphingosine, which are highly bioactive compounds that affect cellular regulatory pathways; 2) addition of sphingomyelin to a standard AIN diet (which is essentially devoid of sphingolipids) reduces the appearance of aberrant colonic crypts, and perhaps the number of tumors, in mice treated with a colon carcinogen; and 3) an enzyme of sphingolipid metabolism has been discovered to be the target of a class of toxic and carcinogenic mycotoxins called fumonisins. Given these recent findings, it is possible that some of the confusion that has arisen regarding the relationships between dietary fat and disease might be due to the lack of consideration of the sphingolipids that are also present. PMID- 7782926 TI - Modulation of signal transduction in macrophages by dietary fatty acids. AB - Tumor growth can be altered by the amount and type of fat in the diet. Although there are several possible mechanisms for this, recent work suggests that alterations in the immune system by dietary fat may affect tumorigenesis. The focus of recent studies has been on dietary fat modulation of macrophage function because that cell plays a pivotal role in many immune responses, including anti tumor activity. One possible mechanism of dietary fat effects on macrophages is altered signal transduction, which, in turn, could alter gene regulation and macrophage function. Initial studies tested the effects of dietary fat on kinase activity after stimulation with interferon-gamma. Macrophages from mice fed menhaden fish oil (MFO) had slightly decreased protein kinase C activity compared with macrophages from mice fed safflower oil (SAF). No differences among the diets were observed when the activity of protein kinase A and G were tested. When calcium mobilization was tested, we found that macrophages from mice fed MFO had an increased response compared with macrophages from mice fed SAF. Dietary fat also modified the response of macrophages to platelet-activating factor with respect to the induction of Ia expression. In studies to identify genes involved in dietary fat effects on macrophage function, we screened a cDNA library of macrophages treated with prostaglandin E2 (PGE2), a lipid-based mediator that can modulate macrophage function and be altered by dietary fat. The cloned gene, BTG1, was enhanced in macrophages treated with PGE2, but the relationship with dietary fat remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782927 TI - Pleiotropic Actions of 1 alpha, 25-dihydroxyvitamin D3: an overview. PMID- 7782928 TI - Genomic actions of 1,25-dihydroxyvitamin D3. AB - Recent studies have identified a heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) as the active complex for mediating positive transcriptional effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active hormonal form of vitamin D. The VDR-RXR heterodimer has been shown to bind to direct repeat vitamin D-responsive elements (VDREs) upstream of positively controlled genes in the target tissues for vitamin D, including bone (osteocalcin, osteopontin, and beta 3 integrin), kidney (24-hydroxylase) and intestine (calbindin). Residues that participate in heterodimer formation have been identified in the C-terminal hormone-binding domain by analysis of VDR mutants. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is not entirely clear, but studies of two natural VDR mutants suggest that the binding of both hormone and RXR are required to induce a receptor conformation that is competent to activate transcription. A final level of complexity is added by recent observations that VDR is modified by phosphorylation. Thus, the VDR-mediated action of 1,25(OH)2D3 is now known to involve multiple factors that may provide a conceptual basis for future understanding of the tissue-specific genomic effects of 1,25(OH)2D3. PMID- 7782929 TI - Nongenomic effects of 1,25-dihydroxyvitamin D3: potential relation of a plasmalemmal receptor to the acute enhancement of intestinal calcium transport in chick. AB - A number of model systems now exist for studying the nonnuclear actions of the seco-steroid hormone 1,25(OH)2D3. The perfused duodenal loop of vitamin D-replete chicks has provided the best correlation between nonnuclear actions and a physiological end point, namely enhanced calcium transport. Recent progress has been made in identifying and purifying an integral protein of the basal lateral membrane that may be a receptor for 1,25(OH)2D3. Studies with analogues (particularly 1,25(OH)2-7-dehydrocholesterol and 1,25(OH)2-lumisterol3) have provided definite correlations between binding to the solubilized membrane receptor and the ability to initiate transcaltachia (the rapid hormonal stimulation of calcium transport). PMID- 7782930 TI - Vitamin D metabolites modulate osteoblast activity by Ca+2 influx-independent genomic and Ca+2 influx-dependent nongenomic pathways. AB - Previous studies have shown that 1,25(OH)2D3 activates multiple signaling pathways in osteoblasts, including rapid nongenomic and long-term genomic pathways. Genomic pathways are mediated by the vitamin D receptor (VDR), a member of the steroid receptor superfamily, and involve transcriptional regulation of target genes. Nongenomic pathways involve lipid turnover, activation of Ca+2 channels and elevation of intracellular Ca+2, all of which occur within seconds after addition of seco-steroid. The interaction of other physiological metabolites of vitamin D, such as 24,25(OH)2D3, with target cells such as osteoblasts is much less clear. We have used a combination of electrophysiological, biochemical, molecular and ion tracer studies to dissect the physiological responses of osteoblast-like osteosarcoma cells (ROS 17/2.8) to 1,25(OH)2D3 and related metabolites. We conclude the following: 1) the structural requirements for activation of genomic vs. nongenomic pathways by seco-steroid are distinct and likely to involve separate receptors; 2) activation of rapid nongenomic pathways is independent of the long-term regulation of target genes; and 3) 1,25(OH)2D3 and 24,25(OH)2D3 interact at the level of the plasma membrane to regulate Ca+2 permeability. Present studies are aimed toward the understanding of the role of both genomic and nongenomic pathways in osteoblast physiology. PMID- 7782931 TI - Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2-D3] is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25 (OH)2-D3 and analogue, 1,25-dihydroxy-16ene-vitamin D3 [1,25-(OH)2-16ene-D3], on T helper subsets type 1 (Th1) or type 2 (Th2) that have distinctive functional characteristics in humans. Th1 secrete interferon (IFN-gamma), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG2a while Th2 secrete IL-4, IL-10 and induce the production of IgG1 and IgE by B cells. The sterol inhibits the secretion of IL-12, a cytokine produced by monocytes and B cells, which leads to the activation and differentiation of Th1. In addition, 1,25-(OH)2-D3 directly inhibits IFN-gamma secretion by Th1 clones while it has little effect on IL-4 secretion by Th2 clones. The analogue, 1,25-(OH)2-16ene-D3, is 100-fold more potent than 1,25-(OH)2-D3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prevents the induction of spontaneous and induced autoimmune diseases and inhibits Th1 induce IgG2a responses. These actions of the vitamin D3 compounds suggest that it may have potential therapeutic applications in Th1-mediated clinical situations such as autoimmunity and transplantation. PMID- 7782932 TI - 1,25(OH)2D3-regulated human keratinocyte proliferation and differentiation: basic studies and their clinical application. AB - Keratinocytes produce vitamin D, metabolize it to its most biologically active form, 1,25(OH)2D, and respond to the 1,25(OH)2D they produce with a decrease in proliferation and an increase in differentiation. 1,25(OH)2D production by keratinocytes is tightly controlled and changes as the cells differentiate, increasing during the early stages of differentiation and then decreasing again as terminal differentiation ensues. The 1,25(OH)2D produced endogenously or supplied exogenously acts in concert with calcium and products of phosphoinositide metabolism to stimulate the transition from a proliferating basal cell to a terminally differentiated corneocyte. The mechanisms involved include changes in gene transcription and messenger RNA stability. These antiproliferative, prodifferentiating actions of 1,25(OH)2D3 have led to its successful use in psoriasis, a hyperproliferative skin disease, and may lead to its use as a chemopreventive agent in malignancy. PMID- 7782933 TI - Insulin resistance, obesity and hypertension: an overview. PMID- 7782934 TI - Insulin resistance, obesity and hypertension. AB - Although controversy exists as to the role that insulin resistance and hyperinsulinemia play in the pathogenesis of hypertension, data are presented that strongly suggest that selective insulin resistance and hypertension are directly related. This paper summarizes how insulin resistance may be linked to obesity hypertension and describes some of the other cardiovascular implications that insulin resistance may have in the hypertensive obese individual. PMID- 7782935 TI - Obesity and hypertension: roles of hyperinsulinemia, sympathetic nervous system and intrarenal mechanisms. AB - Hypertension is a well-recognized complication of obesity. However, the mechanisms for the development of obesity hypertension are not known. One mechanism proposed is that the hyperinsulinemia present in obese hypertensive patients causes hypertension via sodium retaining and/or sympathetic nervous system stimulatory effects. However, numerous studies in dogs have revealed no evidence for such chronic pressor actions of hyperinsulinemia. This is in close agreement with studies in human insulinoma patients that show marked hyperinsulinemia and normal blood pressure. The appropriateness of the dog as an experimental model is strengthened by reports from our laboratory and others that inducing obesity in dogs reproduces many of the characteristics of obesity in humans, including insulin resistance, hyperinsulinemia, sodium retention, hypertriglyceridemia and hypertension. Recent studies in obese dogs have indicated that significant increases in renal medullary cellularity and intercellular matrix deposition could contribute to the sodium retention and hypertension. Additional evidence suggests that sympathetic nervous system stimulation also may contribute to the elevated blood pressure. However, the mechanisms through which obesity induces these changes and the temporal relationship between these factors and the development of the hypertension remains to be determined. PMID- 7782936 TI - Insulin inhibits dog vascular smooth muscle contraction and lowers Ca2+i by inhibiting Ca2+ influx. AB - Essential hypertension, obesity and non-insulin-dependent diabetes are associated with resistance to insulin-induced glucose disposal. Because physiological concentrations of insulin inhibit vascular smooth muscle (VSM) contraction in vivo, it has been proposed that resistance to insulin-induced inhibition of VSM contraction might be partly responsible for the elevated vascular resistance found in these clinical conditions. Nevertheless, it is not known how insulin inhibits contraction of normal VSM. Several workers have demonstrated that insulin attenuates the agonist-induced intracellular Ca2+ (Ca2+i) transient in VSM, although the identity of the sarcolemmal and/or sarcoplasmic reticular Ca2+ transport systems that are affected by insulin is controversial. Our laboratory has examined the effects of a physiological concentration of insulin on contraction and Ca2+ transport in cultured VSM cells from canine femoral artery. We have found that insulin inhibits agonist-induced contraction and attenuates the agonist-induced Ca2+i transient by inhibiting Ca2+ influx, but not by increasing Ca2+ efflux or inhibiting Ca2+ release from internal stores. Insulin also stimulates ouabain-sensitive 86Rb+ uptake (Na(+)-K+ pump activity) and does not inhibit VSM contraction in the presence of ouabain. Our data support the hypothesis that insulin stimulates Na(+)-K+ pump activity, resulting in hyperpolarization of the cell and decreased Ca2+ influx via voltage-operated channels. PMID- 7782937 TI - Insulin resistance vs. hyperinsulinemia in hypertension: insulin regulation of Ca2+ transport and Ca(2+)-regulation of insulin sensitivity. AB - Hypertension in obesity and insulin resistance has been attributed to insulin stimulation of sympathetic neural output and renal sodium retention. However, recent data demonstrates a significant vasodilatory effect of insulin and suggests that vascular smooth muscle resistance to this action may instead be the cause of hypertension in insulin resistance. This concept is supported by the observation that pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. Insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle relaxation, while these effects are blunted in obesity and insulin resistance. Insulin regulation of vasoconstriction and vascular relaxation appears to be secondary to regulation of intracellular Ca2+ ([Ca2+]i), as insulin attenuates both voltage- and receptor-mediated Ca2+ influx and stimulates both the transcription and activity of Ca(2+)-ATPase in vascular smooth muscle cells. Further, these effects are also blunted in insulin resistance. Although [Ca2+]i plays a poorly understood role in insulin signalling, increases beyond an optimal range results in impaired insulin sensitivity, possibly by Ca(2+)-inhibition of insulin-induced dephosphorylation of insulin-sensitive substrates. Consistent with this concept, ectopic overexpression of the agouti gene in the viable yellow (Avy) mouse results in increased skeletal myocyte [Ca2+]i. Accordingly, increased [Ca2+]i in primary insulin target tissues appears to result in peripheral insulin resistance which then results in aberrant regulation of vascular smooth muscle [Ca2+]i and increases in arterial pressure. PMID- 7782938 TI - Alpha-keto acid dehydrogenase complexes: nutrient control, gene regulation and genetic defects. Overview. PMID- 7782939 TI - The pyruvate dehydrogenase complex: nutrient control and the pathogenesis of insulin resistance. AB - This review examines the molecular mechanisms underlying substrate competition between glucose and lipid in starvation and in insulin-resistant states. We demonstrate that lipid-derived substrates are oxidized in preference to glucose by skeletal muscle in vivo during prolonged starvation. An accelerated and exaggerated lipolytic and ketogenic response to starvation in late pregnancy is associated with more rapid suppression of glucose oxidation by the maternal skeletal-muscle mass. These benign adaptations to changes in lipid availability (which occur secondarily to changes in carbohydrate supply and demand) contrast with the well-documented detrimental effects to health of an inappropriately high supply of dietary lipid. We present results that indicate that the prolonged consumption of a diet high in saturated fat is associated with a stable enhancement of pyruvate dehydrogenase (PDH) kinase activity at least in two oxidative tissues--liver and heart. This long-term enhancement of PDH kinase activity is concomitant with the development of whole-body insulin resistance and adds a new dimension to the potential role of dietary composition in the pathogenesis of insulin resistance. PMID- 7782940 TI - Gene regulation and genetic defects in the pyruvate dehydrogenase complex. AB - The mammalian pyruvate dehydrogenase complex (PDC) is subject to both short-term (product inhibition and covalent modification) and long-term (increases in total activity and protein mass) regulation mediated by dietary and hormonal treatments. Recent advances in the isolation and characterization of the complementary DNAs as well as genes encoding several components of mammalian PDC have facilitated studies concerning long-term regulation of PDC. Analyses of the promoter-regulatory regions of the two human PDC genes show characteristics of both facultative and housekeeping gene promoters, indicating complex transcriptional regulation. Deficiency of PDC activity causes a wide range of neurological disabilities. A spectrum of genetic defects in PDC components has been reported; however, the most frequent defects are associated with the pyruvate dehydrogenase component. Heterogeneity in pyruvate dehydrogenase deficiency has been shown to occur at both protein and messenger RNA levels, and several mutations in pyruvate dehydrogenase have been identified. Dietary treatments such as ketogenic diets and vitamin supplements as well as dichloroacetate treatment have been utilized to treat PDC deficiency, but their efficacy requires further evaluation. PMID- 7782941 TI - Nutritional regulation of the protein kinases responsible for the phosphorylation of the alpha-ketoacid dehydrogenase complexes. AB - The branched-chain alpha-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) complexes are regulated by phosphorylation cycles catalyzed by complex-specific protein kinases and phosphoprotein phosphatases. Molecular cloning of these mitochondrial protein kinases has established a new family of protein kinases in eukaryotes that appears related by primary sequence to the histidine protein kinase family of prokaryotes. Changes in the activities of both kinases that are stable, i.e., not caused directly by allosteric effectors, correlate inversely with the changes in the activity states of the complexes that occur in different nutritional states. For example, BCKDH kinase activity is increased and the BCKDH complex activity state is decreased in rats fed diets deficient in protein. The increase in BCKDH kinase activity is due to an increase in the amount of BCKDH kinase protein bound to the BCKDH complex. The message level for BCKDH kinase also increases in the liver of rats starved for protein, suggesting a pretranslational mechanism exists for the long-term regulation of BCKDH kinase. Starvation and high-fat feeding cause a stable increase in PDH kinase activity and a corresponding decrease in activity state of the PDH complex. The mechanism responsible has not been defined. PMID- 7782942 TI - Branched-chain alpha-keto acid dehydrogenase complex in rat skeletal muscle: regulation of the activity and gene expression by nutrition and physical exercise. AB - Branched-chain alpha-keto acid dehydrogenase complex is the rate-limiting enzyme in the catabolism of branched-chain amino acids in skeletal muscle. It is suggested that activation of this enzyme in the muscle during exercise plays an important role in the increased oxidation of branched-chain amino acids in the muscle. Evidence suggests that branched-chain alpha-keto acids, the substrates for the enzyme, regulate the activity state of the enzyme in the muscle during exercise through phosphorylation/dephosphorylation cycle of the enzyme protein. We propose a model for the mechanism of enzyme activation by exercise. In addition to this acute effect of exercise, we present evidence suggesting that exercise training modulates the enzyme activity and gene expression for the enzyme. Increases in the total activity as well as enzyme proteins by exercise training are suggested to be associated with mitochondrial biogenesis in the muscle. PMID- 7782944 TI - Thyroid hormones, their activation, degradation and effects on metabolism. AB - The control of both metabolism and developmental events by thyroid hormones involves a variety of metabolic modifier effects. These actions of thyroid hormones are mediated by nuclear thyroid hormone receptors that have their highest affinity for triiodothyronine (T3). Thyroid hormone deiodinations can have activating or inactivating effects, with the production of T3 (the most active form) and its degradation being of key importance. At the organismic level, the development of thermogenic metabolic responses necessary for homeothermy in birds is correlated with the pattern of thyroid development and the extrathyroidal deiodinations of thyroid hormones. At the cellular level, deiodination effects on cellular T3 availability can protect T3 supply for critical developmental processes (e.g., in brain) or potentially play a role in the differentiation and maturation of various hormone-responsive tissues. Thyroid hormones, both alone and through interactions with other hormones and growth factors, also can influence intermediary metabolic responses that, in turn, play roles in growth and development. PMID- 7782943 TI - Molecular basis of maple syrup urine disease and stable correction by retroviral gene transfer. AB - Maple syrup urine disease (MSUD) or branched-chain ketoaciduria is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. This results in the accumulation of the branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA), which often produce severe neurological damage and mental retardation. The present studies focus on mutations in the E1 alpha gene of the BCKAD complex and their effects on the assembly of the E1 decarboxylase component of the enzyme complex. We have developed an efficient histidine-tagged bacterial expression system that allows the folding and assembly of E1 alpha and E1 beta subunits into the E1 heterotetramer (alpha 2 beta 2) in the presence of overexpressed chaperonins GroEL and GroES. The results of pulse chase experiments with this bacterial expression system showed that a majority of the 15 known E1 alpha mutations, including the prevalent Y393N of Mennonite MSUD patients, decrease the rate of association of normal E1 beta with mutant E1 alpha. This results in limited or no assembly of mutant E1. It is concluded that the carboxy-terminal region of the E1 alpha subunit encoded by exons 7-9 is important for subunit interaction. To stably correct MSUD, we have developed a retroviral vector that contains a normal E1 alpha precursor complementary DNA. Transduction of cultured lymphoblasts from a Mennonite MSUD patient with this recombinant retroviral vector completely restored the rate of decarboxylation of BCKA. The normal decarboxylation activity in transduced MSUD cells remained stable without antibiotic selection during the 14-week study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782945 TI - Species variation in mechanisms for modulation of growth by beta-adrenergic receptors. AB - Beta-adrenergic agonists have been fed to avian and mammalian species to modulate growth. Such treatment produces increased rate of gain, decreased feed consumption, increased skeletal muscle and decreased fat accretion. There is good evidence for the inhibition of adipose tissue lipogenesis and stimulation of lipolysis as well as stimulation of skeletal muscle protein synthesis and inhibition of degradation. Other effects include increased blood flow and modulation of plasma concentration of various hormones. The degree to which each of these effects is observed varies considerably between experiments. Some of the diversity may be explained by species and/or tissue differences in distribution of beta-adrenergic receptor subtypes, in structure and, consequently, in response of receptors and in the pharmacodynamics of the agonist. In addition, several different agonists have been used, adding further complexity. Oversimplification by extrapolation of research observations across species and agonists may confuse attempts to derive mechanisms for the growth modulation effects of beta adrenergic agonists in vivo. PMID- 7782946 TI - Proposed mechanisms for the regulation of growth hormone action in poultry: metabolic effects. AB - Growth hormone (GH) administration to nonruminant red meat animals markedly alters carcass composition so that dramatic reductions in adipose tissue accretion and enhancement of lean tissue growth occur. These repartitioning effects of GH in the pig are reported to reflect antagonism of the lipogenic effect of insulin on adipose tissue, the primary site of fatty acid synthesis in this species, so that glucose disposal and utilization by adipose tissue are markedly reduced, and substrate availability to muscle is increased. In poultry, a significant positive response to GH administration is not consistently achieved, and factors such as posthatch period of development and the pattern of tissue exposure to GH are important determinants of the response to GH enhancement. This may relate to the status of target tissue GH receptors that appear subject to down regulation in the adult chicken. Sensitivity of the bird to the appetite-suppressive effects of GH and interaction between this effect and energy intake have recently been demonstrated and need to be further explored. Growth hormone clearly influences hepatic lipogenesis and net lipid deposition in the broiler chicken. However, future research emphasis on the regulation of GH receptor binding activity and gene expression and their relationship to GH action, as well as on newer components of the GH axis such as GH-binding proteins, will help to clarify controlling mechanisms in poultry. PMID- 7782947 TI - Beyond deficiency: new views of vitamins in ruminant nutrition and health: an overview. PMID- 7782948 TI - Supranutritional administration of vitamins E and C improves oxidative stability of beef. AB - Vitamins E and C are important antioxidants in animals. Their antemortem activity continues to function in postmortem muscle (meat), where they have a critical role in maintaining quality in the food product. Dietary supplementation of vitamin E, and intravenous infusion of vitamin C immediately before harvest, are efficacious techniques for increasing the concentration of these vitamins in beef skeletal muscle. Meat with elevated levels of either and probably both of these antioxidant vitamins possesses greater stability of oxymyoglobin and lipid, which results in less discoloration and rancidity, respectively. A model is proposed for the redox relationships between myoglobin and phospholipid in beef with emphasis on vitamins E and C. Antemortem nutritional intervention appears to be a promising approach for improving the quality of fresh meat products subsequently obtained from livestock. PMID- 7782949 TI - Bioavailability and interaction of vitamin A and vitamin E in ruminants. AB - Recent interest in antioxidant vitamins and animal nutrition has resulted in the investigation of feeding levels of vitamin E which are considerably higher than NRC requirements. Relatively high levels of vitamin E are required to improve animal product quality such as extending beef color stability and minimizing off flavors in milk due to lipid oxidation. Concerns regarding a negative effect of vitamin A on vitamin E utilization and the suitability of currently used standard activity values for vitamin E supplements for ruminants have been raised. High dietary levels of vitamin A have depressed vitamin E utilization in most animals studied. In the dairy cow, 675,000 IU of vitamin A acetate per head per day is required to significantly depress vitamin E utilization. This is approximately 10 fold greater than the highest levels currently fed to dairy or beef cattle and therefore should not cause a practical problem. Synthetic and naturally derived alpha-tocopherol, and their ester forms, are commonly used as vitamin E supplements. These various forms give rise to isomer differences, ester differences and formulation differences that can affect their absorption and subsequent utilization. The current research indicates that the commonly used standard activity values based on a value of 1.00 IU per mg of all-rac-alpha tocopheryl acetate are probably too low for the ruminant. The roles of isomeric forms and gastrointestinal tract absorption have not been completely resolved regarding their effects on the bioavailability of vitamin E supplements. PMID- 7782950 TI - Antioxidant vitamins affect food animal immunity and health. AB - Carotenoids (beta-carotene and lycopene), vitamin E (alpha-tocopherol) and vitamin C (ascorbate) are naturally-occurring antioxidant nutrients that play important roles in animal health by inactivating harmful free radicals produced through normal cellular activity and from various stressors. Both in vitro and in vivo studies showed that these antioxidant vitamins generally enhance different aspects of cellular and noncellular immunity. The antioxidant function of these micronutrients could, at least in part, enhance immunity by maintaining the functional and structural integrity of important immune cells. A compromised immune system will result in reduced animal production efficiency through increased susceptibility to diseases, thereby leading to increased animal morbidity and mortality. PMID- 7782951 TI - Women's health: nurses pave the way. PMID- 7782952 TI - When a baby dies: rights of the baby and parents. AB - The Rights of Parents When a Baby Dies and Rights of the Baby were developed by the Perinatal Bereavement Team at Women's College in Toronto, Canada. With permission, the National Office of SHARE: Pregnancy and Infant Loss Support, Inc. has revised and expanded these documents for distribution within the United States. The Rights are intended to help caregivers and institutions provide parents with information about their options regarding the death of their baby and allow them time and support for decision making. PMID- 7782953 TI - Pneumothorax in the neonate. AB - Neonatal critical-care nurses frequently care for neonates experiencing pneumothoraces. The treatment of a pneumothorax varies with the cause. Knowledge of the condition will help the nurse in caring for the neonate at high risk. In this article, types of pneumothoraces will be reviewed, and information will be provided regarding the pathophysiology, diagnosis, treatment, and nursing responsibilities in caring for an infant experiencing a pneumothorax. PMID- 7782954 TI - Physiologic measures of kangaroo versus incubator care in a tertiary-level nursery. AB - OBJECTIVE: To determine the safety and feasibility of kangaroo care in a tertiary level nursery as defined by apnea, bradycardia, and oxygen desaturation. DESIGN: Prospective, long-term, repeated measures with a convenience sample. SETTING: A 20-bed, tertiary-level nursery with approximately 400 admissions a year. PARTICIPANTS: Eight mother-infant pairs. INTERVENTIONS: Researchers compared incubator care with kangaroo care for 4 hours a day, 6 days a week, for 3 weeks. Physiologic variables were monitored daily and recorded continuously on a polygraph for 8 hours each week. MAIN OUTCOME MEASURES: Amount of apnea, bradycardia, and oxygen desaturation. SECONDARY OUTCOME MEASURES: Heart rate, respiratory rate, percent sleep time, and skin temperature. RESULTS: Apnea, bradycardia, oxygen saturation, heart rate, and respiratory rate were similar during both kangaroo (K) and incubator (I) care. The infants experienced a lower percent (mean +/- standard deviation, K versus I) of total sleep (47 +/- 15 versus 64 +/- 19, p < .003) during kangaroo care. The infants' mean +/- standard deviation temperature during the kangaroo care (36.5 degrees C +/- 0.64 degrees C) was lower (p < .03) than that of the control periods before (36.8 degrees C +/ 0.27 degrees C) or after (36.7 degrees C +/- 0.26 degrees C). Percent sleep time and skin temperature were slightly lower during kangaroo care, but the differences were not clinically significant. CONCLUSION: Kangaroo care is safe and feasible for selected mothers and infants in a tertiary-level nursery. PMID- 7782955 TI - Sleep disturbances and fatigue in women with fibromyalgia and chronic fatigue syndrome. AB - OBJECTIVE: To determine the relationship between sleep disturbances and fatigue in women with fibromyalgia (FM) and those with chronic fatigue syndrome (CFS) and to assess whether any differences existed between the two groups. DESIGN: Descriptive comparative. SETTING: Community program on chronic fatigue syndrome and related disorders. PARTICIPANTS: Sixty-three women who attended the program; 13 had CFS, and 50 had FM. MAIN OUTCOME MEASURES: A moderately strong relationship between fatigue and sleepiness was found (r = .63, p < .01). Trouble staying asleep was the highest rated sleep disturbance, and fatigue was the most common subjective feeling reported. Women with CFS reported significantly more trouble staying asleep than women with FM, t(61) = 1.81, p < .03. CONCLUSIONS: Data from this study support that women with FM and CFS encounter problems sleeping. Clinicians are encouraged to assess women with FM and CFS for their quality of sleep rather than amount of sleep. Researchers are encouraged to continue study of sleep disturbances in women with FM and CFS to improve understanding of the disturbances and to test the effectiveness of sleep interventions. PMID- 7782956 TI - Maternal learning needs during labor and delivery. AB - OBJECTIVE: To determine if the learning needs of mothers are met by nurses during labor. DESIGN: Descriptive survey with a longitudinal time frame. SETTING: Two hospitals in a midsized Canadian city. PARTICIPANTS: Fifty-seven women in their last month of pregnancy, selected at random from 276 eligible women referred by physicians. Final sample for analysis was 40. MAIN OUTCOME MEASURES: Data described patients, their expected learning needs before delivery, the teaching they received, and factors related to the experience. RESULTS: The majority of subjects wanted teaching in labor and reported that teaching was helpful, but that conflicts in teaching and differing expectations of staff were upsetting. Mothers' expectations and the teaching they received were congruent for some topics and incongruent for others. CONCLUSION: Results suggest a need for assessment of learning needs of women in labor, consistency among caregivers, and further study with a larger sample. PMID- 7782957 TI - Cultural concepts of women's health and health-promoting behaviors. AB - Cultural diversity is the reality of the 1990s, and the United States is becoming the most ethnically diverse society in the world. The needs and responses of many different racial and ethnic groups are competing for recognition, and nurses must learn how to meet the health care needs of this multicultural society. This article explores cultural concepts relating to women's health and health promoting behaviors in the context of this social change. It explores demographic change, concepts of heritage consistency, traditional health beliefs, and traditional health-promoting behaviors. PMID- 7782958 TI - Intercultural communication: finding common ground. AB - Diversity has become a leading topic of discussion in virtually all sectors of our society. This is certainly true in health care; the nursing profession has long been dealing with issues of cultural appropriateness. This article looks at the relationship of culture to communication. The current approach to intercultural communication discussed in much of the nursing literature is judged to be short-sighted. An alternative approach based on the development of a functional cultural communication perspective is offered. PMID- 7782959 TI - Culture, spirituality, and women's health. AB - A review of the literature on culture, health/women's health, and spirituality/religion reveals that the purported relationships among these variables may be tenuous. Nevertheless, there is a need for health care professionals to be aware of existing cultural/religious beliefs that may affect women's health behavior if provision of holistic health care is a goal. Implications for practice and research can be drawn from the existing evidence in the literature. PMID- 7782960 TI - Migrant and seasonal farm worker women. AB - Migrant and seasonal farm worker women are part of a population whose health care needs are underserved. This article provides some definition of this population and reviews some of the health needs specific to them. The significant need for outreach to and assessment of this population is addressed. The significance of the nurse's role is addressed. The need for health care services being delivered in a culturally sensitive manner is discussed. Resources to assist health care providers in providing more effective interventions and referrals for care of migrant and seasonal farm worker women are identified. PMID- 7782962 TI - Right diaphragmatic paralysis following orthotopic liver transplantation. AB - Although most postoperative complications of liver transplantation are well known and their pathophysiology is reasonably understood, right diaphragmatic dysfunction occurring after liver transplantation remains an unappreciated complication. To evaluate the incidence and mechanisms responsible for such injury, a group of 48 liver transplant patients were studied prospectively. Partial right diaphragmatic paralysis was found in 11 (23%), complete paralysis was found in 10 (21%) and the remaining 27 patients had normal diaphragmatic motion (56%). The operative records of these 48 patients were reviewed. Right diaphragmatic injury was found to be a common postoperative complication of liver transplantation. Moreover, it was found to have a clinically significant effect upon the postoperative course of these patients, often necessitating a prolonged ICU stay and prolonged ventilatory support. Although the exact mechanism responsible for its occurrence remains speculative, careful attention to operative technique particularly in the dissection of the upper cava and careful closure of the bare area of the diaphragm, may reduce the frequency of this untoward complication. PMID- 7782961 TI - How much is too much? A study of pregnant women in service industry jobs. AB - This qualitative study explored the broad aspects of stress and coping in the work and home experiences of pregnant women who worked in the service industry. The participants described home roles of mother, spouse/partner, and homemaker that were particularly valued and significant. Work provided income and a cultural setting for socialization, personal growth, and social support. The participants coped with the additional demands of pregnancy by adopting health promotion measures and scheduling routines at work and home in different ways. However, pregnant working women often are pulled in many directions at once, and their health eventually may be affected. PMID- 7782963 TI - The Oklahoma-Pittsburgh experience with interferon alpha in the treatment of HCV disease. AB - Interferon alpha (IFN) is the only Food and Drug Administration (FDA)-approved therapy available for the treatment of chronic hepatitis C. The ideal dose and frequency of IFN administration that produces the greatest number of patient responders with the least number of relapses following drug withdrawal remains unclear. METHODS. One hundred seventeen patients recruited over a five-year period with chronic hepatitis C were divided into four groups and treated with progressively larger doses. The rate of clinical responses defined as a loss of detectable hepatitis C virus-ribonucleic acid (HCV-RNA) in serum by polymerase chain reaction (PCR) and normalization of the serum ALT (abnormal alanine aminotransferase) for each group was calculated. RESULTS. As the dose of IFN administration increased, the response rate defined by the absence of HCV-RNA in the patient's serum after six months of follow-up increased from 7.7% to 26.6%. If the end point utilized was HCV-RNA negativity after six months of treatment, the response rate varied from 19.2% to 30%. Using the less difficult end point of a normal ALT level, the response rates varied from 32.1% to 63.3% after six months of therapy and from 10.7% to 26.7% after six months of follow-up. CONCLUSIONS. This experience demonstrates that both the response rate at the end of therapy and after six months of follow-up improves with an increase in dose of IFN administered over a six-month period. PMID- 7782964 TI - A note in support of reversal treatment for coronary artery disease. AB - Coronary heart disease is the leading cause of mortality and morbidity in the United States at an estimated cost of $56 billion per year. Current approaches to treatment of coronary artery disease are not likely to reduce mortality and morbidity despite pressure to reduce costs in the changing health care environment. Evidence is now available that comprehensive noninvasive medical management, which includes aggressive lipid-lowering therapy, can produce results equivalent to current approaches at a lower cost. The author supports this approach, which can prevent progression and possibly produce regression of coronary artery disease. A new approach to management is proposed that integrates comprehensive noninvasive management as initial therapy for coronary heart disease. PMID- 7782965 TI - [Management of hypopharyngeal and cervical esophageal cancer (HCEC): a comparative study of primary-surgical and primary-radiotherapeutic regimens]. AB - The results of two treatment regimens for HCEC were compared. Surgery played a main role in the first regimen (Group A), in which patients underwent total pharyngo-laryngo-esophagectomy (with bilateral neck dissection and primary reconstruction by pectoralis major myocutaneous flap or gastric tube) after receiving 20 Gy of irradiation therapy. Chemotherapy was combined in some patients. In the second regimen (Group B), radiation was employed as the main treatment in order to conserve the larynx. Chemotherapy (UFT 300 to 600 mg/day; in some patients one or two courses of intra-venous cisplatinum therapy) was combined with radiation therapy (60 Gy) to improve the effectiveness of this regimen. In case of radiation failure, a salvage operation was performed. We investigated 60 HCEC patients who visited the Kitasato University Hospital during the period from 1983 to 1992. The tumor was located in the PC, PS, PW, and Ce areas in 3, 48, 5, and 4 patients, respectively. There were 25 cases in group A and 35 in group B. Five-year cumulative survival rates were 52% and 55%, respectively. In group B, tumor remained or recurred after the initial treatment in 13 patients. Three patients refused to receive salvage operation. Four of the 10 patients who received salvage operation became tumor free. The larynx preservation rate was 71% in group B. From the standpoint of improving QOL, the group B regimen is recommended. PMID- 7782967 TI - [Study of standing exactitude determined by the scatter of the center of pressure -study of standing exactitude by center of pressure]. AB - In so far as stance is maintained during various activities, the center of pressure must be maintained with a certain area. This area is the range of the center of pressure. It is influenced by standing conditions and vision. In this study we used a force platform to measure the range of the center of pressure in 10 normal adults during maximal voluntary shifting from right to left, back and forth under 6 conditions (standing conditions: both legs apart, both legs together and standing on one leg; vision: eyes open and eyes closed). We also recorded the center of pressure while standing still for 30 seconds under the above 6 conditions. The scatter of the center of pressure and the range of the center of pressure were compared. Under easy standing conditions, the range of the center of pressure was very large and the center of pressure was concentrated in a small area. The more difficult the standing condition, the smaller the range of the center of pressure, and the wider the scatter of the center of pressure. Under very difficult standing conditions, the range of the center of pressure was almost as large as the area in which the center of pressure was scattered. Since the range of the center of pressure is closely connected with the scatter of the center of pressure, it may be possible to determine the accuracy of stance regulation by analyzing the range of the center of pressure and the scatter of the center of pressure. PMID- 7782966 TI - [Study on vomiting and the vestibulo-autonomic reflex]. AB - When vestibular organs are abnormally stimulated, autonomic reactions such as nausea, vomiting, palpitation, etc., occur, indicating the existence of fiber connections from the vestibular organs to the autonomic centers. The relationship between the "vomiting center" in the medulla oblongata as described by Borison and Wang and the vestibular nucleus remains obscure. To investigate the central mechanism of vomiting caused by vestibular stimulation, the intragastric pressure, gastric peristalsis and respiration during electric stimulation of the medullary vomiting center and the semicircular canal nerve were recorded in 12 adult cats. Evoked potential was also recorded while electrically stimulating the semicircular canal nerve. When the peripheral labyrinth was stimulated, a conflicting result was founded, namely, that the pressure in the stomach increased or decreased. Retching or vomiting-like behavior was observed in several sites when the dorsolateral portion of the reticular formation of the medulla was stimulated. It was found that neural structures in the dorsolateral portion of the reticular formation of the medulla were associated with the semicircular canal nerve, but retching or vomiting-like behavior was not always observed during stimulation there. PMID- 7782968 TI - [Tympanosclerosis--clinical and pathological investigation]. AB - Fifty-nine cases of tympanosclerosis were investigated clinically and pathologically, and the following results were obtained: 1) The male to female ratio was about 1:1.8 2) Calcification in the tympanic membrane was most common in the upper quadrants of the pars tensa, and never seen in the pars flaccida. 3) Calcification in the middle ear cavity was most common around the malleus. 4) Chronic otitis media was the most common complication of tympanosclerosis. 5) Preoperative audiometry revealed a stiffness curve with elevated bone conduction thresholds. 6) 54% of the patient had chronic otitis media in the contralateral ear. 7) Microscopic examination revealed calcification in the submucosa of the middle ear. 8) Postoperative hearing was improved in 49 ears (79.7%). Because there was no difference in the average postoperative hearing gain after type I and type III tympanoplasty, type III tympanoplasty is recommended to remove sclerotic masses completely. PMID- 7782969 TI - [Clinical use of EVAR and OVAR by the dumped rotation test--comparison of normal volunteers and patients with unilateral vestibular nerve section]. AB - Horizontal eye movements in response to either earth vertical axis rotation (EVAR) or off vertical axis rotation (OVAR) by a 10 degree tilted axis were recorded in six normal subjects and three patients with unilateral vestibular nerve section. Both trials consisted of acceleration at approximately 400 deg/sec2 until an angular velocity of 180 deg/sec was reached followed by deceleration at -4 deg/sec2 until rotation ceased. This is the so-called dumped rotation procedure. Total numbers of nystagmic beats and the duration of perrotatory nystagmus in these two different trials were compared. The results were as follows: 1) Total numbers of nystagmic beats in OVAR were significantly larger than in EVAR. 2) The duration of perrotatory nystagmus in OVAR was significantly longer than in EVAR. Only the horizontal semicircular canals were stimulated by angular acceleration in EVAR, whereas both otolith organs and semicircular canals were stimulated on changing the position of the head around the direction of the gravity in OVAR. PMID- 7782970 TI - [Combined macro-micro-endoscopic technique (COMMET) in endonasal sinus surgery: II. Objective assessment and results]. AB - To optimize success in sinus surgery, we use a combined macro-micro-endoscopic technique (COMMET). This technique effectively combines use of the headlamp, microscope, and endoscope according to the demands of each anatomical region. Between April 1991 and March 1994, we successfully performed this technique on 461 patients (798 sides). According to CT scans, about 40% of the patients had pansinusitis, and about 30% of the patients had anterior and posterior ethmoiditis combined with inflammation of other sinuses. Hence, severe cases requiring total ethmoidectomy accounted for about 70% of all sides. All patients were operated on under general anesthesia. The objective of this operation was restoration of drainage and ventilation, and then to allow recovery of the reversible mucosal lesions. The goal of surgery was to normalize all paranasal sinuses. In many patients, there is little correlation between postoperative objective findings in the paranasal sinuses and subjective improvement. Therefore, postoperative subjective improvement cannot be used as the criterion for evaluating the improvement of sinus disease. Hence, we established an objective grading system based on CT and endoscopic findings and evaluated improvements in each sinus after drainage and ventilation had been restored. The rates of normalization over 1 year following surgery (mean follow-up time was 19 20 months) were 64% in the frontal sinus, 72% in the anterior ethmoid sinus, 68% in the maxillary sinus, 90% in the posterior ethmoid sinus and 80% in the sphenoid sinus. The results differed from sinus to sinus, suggesting that there are different factors impairing recovery in each sinus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782971 TI - [A morphological study of the human ventricular fold: age-related changes and sex differences]. AB - A morphological study of the human ventricular fold was conducted with special reference to age-related changes and sex differences. The laryngeal specimens examined were obtained from 54 autopsy cases consisting of 27 males and 27 females ranging in age from 20 to 79 years. Each specimen was frontal-sectioned between the anterior and posterior ends of the ventricular fold to yield 8 equal portions. The surface of the entire ventricular fold was reconstructed based on examination of all of the sections, and extent of squamous metaplasia was 3 dimensionally evaluated and expressed in the form of a histological map. In the cases in which smoking history was ascertained, extent of squamous metaplasia was evaluated by the same method. In all of the cases the distribution of the different types of tissues such as glandular, adipose and connective, was examined in the midportion of the specimen (section No. 5). The following conclusions were drawn as a result. 1. The development of squamous metaplasia reached a peak in the middle-age group, particularly in males. The 3-dimensional extension of metaplasia was classified into 4 patterns, however, there were no age-specific differences in pattern, and the posterior-dominant-type and widespread-type were the most common in all age groups. The extension of metaplasia varied with smoking history, suggesting that smoking promotes the extension of squamous metaplasia. 2. Glandular tissue decreased with age, more markedly in females. The distribution of the glandular tissue was classified into 4 patterns. Atrophy of glandular tissue with age occurred in the central area of the ventricular fold, extending to the marginal portion. 3. Collagen fibers decreased slightly with age. Elastic fibers appeared frequently in the lateral portion near the laryngeal ventricle in the aged group. PMID- 7782972 TI - [Improvement of olfactory disturbance by endoscopic endonasal surgery for chronic sinusitis]. AB - Olfactory disturbance is the one of the most important symptoms of chronic sinusitis. In the present study, we followed up the postoperative clinical course of olfactory disturbance in patients who underwent surgery for chronic sinusitis. Ninety patients with severe olfactory disturbance or anosmia who underwent endoscopic endonasal surgery for chronic sinusitis with severe olfactory disturbance or anosmia in the preceding three-year period were enrolled in this study. We obtained a high postoperative improvement rate of 78.8%. We compared and examined our cases' postoperative clinical course concerning their olfactory disturbance and various factors in other patients before and after surgery, and obtained the following results: a) Young patients, 30 years old or under at the time of surgery, showed significantly higher rates of improvement than patients who were 50 years old or more at the time of surgery. b) Even though revision surgery was performed, the improvement rates were almost the same as after the initial surgery. c) Although the Alinamin intravenous olfaction test is regarded as an olfaction threshold test, we have seen quite a few cases in which improvement was achieved despite the absence of a preoperative response to the Alinamin intravenous olfaction test. d) There was no clear correlation between the presence of preoperative lesions of the ethmoid sinus and the olfactory cleft and the improvement rates. e) The cases with unsatisfactory results concerning the paranasal sinuses and nasal cavity--those accompanied by postoperative adhesions of the olfactory cleft, recurrence of polyps, etc.,--showed significantly lower improvement rates than cases with satisfactory postoperative results. During surgery in patients with severe olfactory disturbance, we conclude that it is particularly important to adequately clean the lesions of the olfactory cleft and the anterior and posterior ethmoid sinus endoscopically. This ensures leaving clear the olfactory cleft. PMID- 7782973 TI - [Vascular reconstruction of the carotid artery--studies of a one stage ipsilateral reconstructive procedure]. AB - Recent advance in vascular surgery have made vascular reconstruction of the carotid artery possible. Since 1990, the authors have performed en bloc resection of the carotid artery and vascular reconstruction of the carotid artery, using a temporary shunt tube, in 10 cases. Among these 10 cases of tumors involving the carotid artery, two cases had carotid body tumors and the other eight cases had metastatic lymph nodes from head and neck cancers. Transient motor paralysis occurred in three cases and disorientation in one after the operation. None has developed severe neurological complications such as death, coma or permanent hemiplegia. Despite preoperative irradiation, local infection was noted in only one case after the operation. Rupture of the vein graft was prevented by using a DP flap to cover dead space at the anastomotic site. The two patients with a carotid body tumor are alive without evidence of recurrence. Among eight patients with cancer, three are still alive and disease free (respectively 44, 30 and 16 months). Two patients died of local recurrence, two of distant metastasis and the other of acute heart failure. Local tumor control was possible in six out of eight patients. We were able to safely perform en bloc resection of the carotid artery and vascular reconstruction of the carotid artery using a temporary shunt tube. In conclusion, we anticipate increasing curability of advanced tumors involving the carotid artery using this procedure. PMID- 7782974 TI - [The effect of cefaclor and cefixime on nasopharyngeal pathogens in children]. AB - Changes in nasopharyngeal flora were investigated in children with acute otitis media and with acute exacerbations of chronic sinusitis in whom antibiotic therapy of relatively long duration was required until substantial improvement in clinical findings was achieved. 1. The antibiotics used were two cephalosporins, i.e., cefaclor (CCL) and cefixime (CFIX), administered to 18 patients each for 1 week and to 26 and 20 patients, respectively, for 2 weeks. Bacteriologic examination of the nasopharyngeal mucosa was performed at the first visit and at 1 week in those who underwent antibiotic therapy for 1 week, and at the first visit and at 1 and 2 weeks in those treated with antibiotics for 2 weeks. 2. The elimination rates for the infecting microorganisms in the patients in the CCL treated group were 30% for Haemophilus influenzae, 83% for Staphylococcus aureus, 100% for Streptococcus pyogenes and 100% for Streptococcus pneumoniae at 1 week, and 18% for H. influenzae, 100% for S. aureus and 100% for S. pyogenes at 2 weeks of antibiotic therapy. Replacement of S. aureus and S. pyogenes by H. influenzae was observed. 3. The elimination rates for infecting bacteria in the patients in the CFIX-treated groups were 61% for H. influenzae, 50% for S. aureus, 75% for S. pyogenes, 80% for S. pneumoniae and 100% for Moraxella catarrhalis at 1 week, and 72% for H. influenzae, 0% for S. aureus, 100% for S. pyogenes, and 0% for S. pneumoniae at 2 weeks of antibiotic therapy. The elimination rate for H. influenzae at 2 weeks was significantly higher than the corresponding value for the CCL-treated group. Replacement of H. influenzae by S. aureus and S. pneumoniae and of S. pyogenes by S. aureus was detected. 4. There was one patient with acute otitis media in the CFIX-treated group in whom a clinical relapse occurred due to H. influenzae persisters in the nasopharynx. Thus the diagnosis in this patient was so-called "recurrent otitis media". 5. H. influenzae tended to persist after exposure to therapeutically adequate concentrations of CCL, as did S. aureus and S. pneumoniae following treatment with CFIX. Thus, it would seem that ample heed must be given to persistence, particularly of H. influenzae and S. pneumoniae, the most common causative agents of acute otitis media in childhood. 6. A significant rise in the MICs of the cephalosporins was observed in 4 of 43 patients in whom the same type of organism was isolated from the nasopharynx at weekly intervals during antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7782975 TI - [Studies on the measurement of the mechanical properties of the round window membrane]. AB - With a microtesting system which can measure the mechanical properties of small tissue membranes, we have measured the mechanical properties of the round window membrane on the guinea pigs and the human. We also found that, as a result of formalin-fixation, round window membranes become weaker and that this effect of formalin-fixation is greater on human round window membranes than on those of guinea pigs. Since the protein in collagen fibers, which are the main constituent of round window membranes, is coagulated and fixed with formalin, we consider that the strength of the membranes decreases and that this is more evident in human membranes, which contain more collagen fiber. Having compared the mechanical properties of the fresh round window membranes of guinea pigs with those of humans, we found that the human membranes are approximately five times stronger than those of guinea pigs. This difference is considered to stem from the species differences. Also, having compared the mechanical properties of the tympanic membranes with those of the round window membranes each species, we found that the round window membranes of guinea pigs are almost the same as their tympanic membranes in terms of strength, whereas human tympanic membranes are stronger and harder than the round window membranes. In view of the minimum pressure causing destruction of human round window membranes, as deduced from the experiment on guinea pigs, it is possible that human round window membranes may be ruptured in the perilymphatic fistula. PMID- 7782976 TI - [Quantitative analysis of smooth pursuit eye movement]. AB - Abnormalities of smooth pursuit eye movement (SPEM) have been estimated, mainly using the wave form on an electro-oculogram, in a qualitative way. Many methods for quantitative analysis of SPEM have been designed, though most are still uncommon in present clinical use. Using a personal computer, we developed a method of automatic quantitative analysis of ocular tracking eye movement recorded by electro-oculography (EOG). The design concept of this method is based on the observation that eye movement during ocular tracking consists of two different kinds of eye movements, one is SPEM and the other is saccade. The combination of SPEM and saccade (composite eye movement: CEM) commonly appears during ocular tracking. These two kinds of eye movement are essentially different not only in behavior but also about involved neural pathway in the central nervous system. From this point of view, we believe that the two kinds of eye movements involved in ocular tracking should be evaluated separately. The analysis method is outlined as follows. A horizontal sinusoidally moving visual target was employed to elicit ocular tracking eye movements. The test frequencies were set at 0.1, 0.2, 0.4 and 0.8Hz, and the amplitude of target motion was 15 deg at each frequency. The 20 seconds of eye movement data measured by EOG were fed into the computer through a digital-analog converter for further analysis. Using our original saccade detection algorithm, based on the physiological behavior of saccades, the saccadic components were detected and removed from the eye movement wave. The remaining parts, fragments of SPEM, were connected by means of interpolating defective parts. The reconstructed wave was a slow cumulative eye position curve (SCEP). Sinusoidal target motion, CEM and SCEP were processed by the FFT (Fast Fourier Transformation) method. Bode plots were applied to summarize the gain and phase of responses to SCEP and the target motion wave. These processes enable us to estimate abnormalities of SPEM such as low gain, abnormal phase shift and large trends in tested duration. We conclude that the method described here is useful for quantitative estimation of SPEM in clinical neuro-otological examinations. PMID- 7782977 TI - Caries lesions and dental restorations as predisposing factors in the progression of periodontal diseases in adolescents. A 3-year longitudinal study. AB - The present study used a novel approach to assess the relationship between untreated caries lesions and defective and non-defective dental restorations and the incidence of gingival inflammation and the progression of chronic inflammatory periodontal diseases at the approximal surfaces of posterior teeth and at the adjacent surface of the neighboring tooth in adolescents over a period of 3 years. Two hundred-twenty-seven (227) 13-year-old schoolchildren were examined clinically and radiographically at baseline and annually at three subsequent occasions. At each site the alveolar bone height and presence of gingival bleeding were assessed. Incipient caries lesions, manifest caries, and defective and non-defective restorations were identified at the same site and also at the adjacent approximal tooth surface at all examinations, both clinically and radiographically. The data were analyzed by the multi-level logistic regression and variance components analyses. On average, 32, 8.5, 7, and 10% of the sites, respectively, were diagnosed as having incipient caries, manifest caries, and defective and non-defective restorations. There was a significant association between the presence of untreated manifest caries lesions, non-defective and defective dental restorations, and the progression of periodontal support loss. Also there was an association between presence of defective restorations and manifest caries and the incidence of gingival inflammation. Consistently, factors detected at the involved site and at the adjacent site had significant effects. The present study indicates that untreated cavities and dental restorations are predisposing factors with a significant negative effect on periodontal health in adolescents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782978 TI - Lack of effect of oral hygiene training on periodontal disease progression over 3 years in adolescents. AB - A comprehensive new oral hygiene training program has lately been described and found effective in controlling dental plaque formation and in significantly reducing the incidence of approximal dental caries and gingivitis in adolescents. This study investigated the long-term effect of plaque control on the progression of periodontal diseases in adolescents. A group of 227 Brazilian schoolchildren were followed up over a period of 3 years. The children were divided randomly into 3 groups. The first group was given a needs-related intensive program which combined detailed information to parents and children pertaining to the etiology and prevention of dental diseases, instructions in self-diagnosis of plaque and gingivitis, and a detailed oral hygiene training based on individual needs, together with continued feedback and motivation during the entire 3 years. The second group was given a similar program, but through shorter sessions and with no motivation and feedback and no training in self-diagnosis. A control group received no motivation sessions or oral hygiene training. The 3 groups were examined radiographically at baseline and annually at 3 subsequent occasions. The data were analyzed with a multi-level variance analysis. The frequency of subjects showing sites with alveolar bone loss increased steadily during the entire period in all groups. Neither of the training programs had a significant effect on the alveolar bone level during 3 years compared to the control group. Generally, girls demonstrated higher proportions of approximal tooth surfaces showing radiographic bone loss, though not statistically significant. In this population the supragingival plaque control lacked any significant effect on periodontal disease progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782979 TI - The modified papilla preservation technique. A new surgical approach for interproximal regenerative procedures. AB - A modification of the papilla preservation technique has been applied to achieve primary closure of the interproximal tissue over barrier membranes placed coronal to the alveolar crest. Fifteen patients with deep intrabony interproximal defects were treated. Defects had a probing attachment level loss of 9.9 +/- 3.2 mm and a recession of the gingival margin of 1.7 +/- 1.6 mm. The depth of the intrabony component was 5.5 +/- 2.9 mm; while the suprabony component was 5.9 +/- 2.0 mm. Titanium-reinforced teflon membranes were placed 1.3 +/- 0.7 mm from the cemento enamel junction, 4.5 +/- 1.6 mm coronal to the interproximal alveolar bone crest. Primary closure over the interproximal portion of the membrane was obtained in 93% of cases. In 73% of the cases complete coverage of the membrane was maintained until its removal at 6 weeks. These data indicate that the modified papilla preservation technique can be successfully applied to obtain primary closure of the interdental space in regenerative procedures with barrier membranes. PMID- 7782980 TI - Collagen formation at the tooth-cell interface: comparative ultrastructural study on the effect of partial demineralization of cementum with dentin. AB - In order to compare the effect of partial demineralization with root planing and partial demineralization of cementum with that of dentin on healing, the ultrastructural morphology of the interface between the layer of human periodontal ligament-derived, fibroblast-like cells (HPF) and the treated root surface was studied in an in vitro culture system. Sixty (60) pairs made from transversally-cut root slices, 500 microns thick, were obtained from extracted human periodontally diseased teeth. Thirty (30) pairs of the root slices were preliminarily root planed (RP). The remaining half were root planed and then partially demineralized in a solution of citric acid (RP+CA). The opposite surface of paired slices was made uniform by using either cementum or dentin. Consequently, all root slices were classified into four experimental groups: RP cementum and RP-cementum pairs (group 1), RP-dentin and RP-dentin pairs (group 2), RP+CA-cementum and RP+CA-cementum pairs (group 3), and RP+CA-dentin and RP+CA dentin pairs (group 4). Each pair of root slices was placed on the floor of a 35 mm culture dish. HPF were seeded at a concentration of 4 x 10(5) cells/dish. Co cultures of HPF and the root slices were examined using phase contrast and electron microscope after 4, 6, and 10 weeks. Electron-dense material covered non demineralized root surfaces and the lining cells in accumulating cell layers were oriented parallel to the root surface and attached to the material in groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782981 TI - Polyamines found in gingival fluid inhibit chemotaxis by human polymorphonuclear leukocytes in vitro. AB - Putrescine and spermidine occur at concentrations approaching 1 mM in gingival fluid at diseased periodontal sites. Previous work demonstrates that these polyamines potentiate Ca2+ signaling in polymorphonuclear leukocytes (PMNs), resulting in enhanced degranulation and superoxide generation. The present study extends this work by characterizing the effects of polyamines on PMN chemotaxis and phagocytosis, in which Ca2+ signaling plays a less defined regulatory role. Putrescine (1 mM) and spermidine (0.1 to 0.5 mM) significantly inhibited chemotaxis to fMet-Leu-Phe and C5a (P < 0.05). This inhibition was not strongly related to any effect polyamines have on PMN adhesion, actin polymerization, or formyl peptide receptor expression. Neither putrescine nor spermidine had a significant impact on phagocytosis of opsonized bacteria by PMNs. Thus, at concentrations similar to those found in gingival fluid, polyamines could potentially inhibit recruitment of PMNs to diseased pockets without impairing their ability to engulf invading bacteria. PMID- 7782982 TI - Modulation by progesterone of interleukin-6 production by gingival fibroblasts. AB - The gingivitis associated with pregnancy has been attributed to increased concentrations of circulating estrogen and/or progesterone. However, the mechanism by which these steroids increase gingival inflammation is not known. Interleukin-6 (IL-6), a pleiotropic cytokine produced by many cell types including human gingival fibroblasts (hGF), is secreted in response to inflammatory challenges such as bacterial lipopolysaccharide and interleukin-1 (IL-1). This study tested the hypothesis that progesterone could modulate the local production of IL-6 by hGF. The effects of progesterone on IL-6 production were measured in vitro in serum-free, phenol red-free medium to eliminate possible effects of such medium additives. The concentration of IL-6 secreted into supernatant medium after a 24 hour challenge with IL-1 beta was estimated by radioimmunoassay. Total RNA from steroid-treated hGF was probed for IL-6 mRNA. In serum-free medium, progesterone dose-dependently and significantly (P < 0.05) inhibited IL-6 production by hGF, as did the glucocorticoids hydrocortisone (HC) and dexamethasone. At progesterone concentrations common in late pregnancy, IL-6 production was reduced to levels 40 to 50% of control. In addition, mRNA was significantly down-regulated by progesterone and HC, at both basal levels and after IL-1 beta challenge. These results suggest that high levels of progesterone during pregnancy affect the development of localized inflammation by down regulation of IL-6 production, rendering the gingiva less efficient at resisting the inflammatory challenges produced by bacteria. PMID- 7782983 TI - Attachment of Fusobacterium nucleatum to fibronectin immobilized on gingival epithelial cells or glass coverslips. AB - To learn more about colonization of the oral epithelium by Fusobacterium nucleatum and the role of fibronectin in mediating adhesion of this microorganism, we studied attachment of this bacterium to cultured gingival epithelial cells that were coated with exogenous, purified plasma fibronectin. The three strains of F. nucleatum studied adhered in large numbers to epithelial cells that had been coated with fibronectin, compared with buffer-coated control cells. Bacterial adherence was also enhanced when epithelial cells were coated with whole human saliva. However, cells coated with saliva depleted of fibronectin did not facilitate adhesion of bacteria. Bacterial adhesion was restored when purified fibronectin was added back. We also tested adherence of bacteria to coverslips coated with fibronectin, saliva, and saliva depleted of fibronectin. The bacteria adhered to coverslips coated with fibronectin or whole human saliva, but did not adhere to coverslips coated with fibronectin-depleted saliva. Bacterial adhesion to coverslips was restored upon addition of purified fibronectin to the fibronectin-depleted saliva. Bacterial attachment to fibronectin-coated coverslips was found to be temperature-dependent, with maximal adhesion observed at 37 degrees C. Pre-treatment of F. nucleatum with soluble fibronectin inhibited attachment of the bacteria by 92%, whereas pre-treatment with bovine serum albumin had no effect. Pre-treatment of bacteria with laminin or type IV collagen caused moderate inhibition of attachment by 60% and 50%, respectively. Treatment of fibronectin-coated coverslips with Fab fragments of anti-fibronectin IgG blocked the attachment of F. nucleatum by 93%. Fab fragments of the other antisera tested had no inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7782984 TI - Mandibular cementifying fibroma in relation to a large periodontal bone defect. Report of a case. AB - A cementifying fibroma associated with a large intraosseous periodontal defect is reported. This tumor was located in the lingual aspect of the first lower left molar. Therapy consisted on flap surgery, tumor excision, and placement of a bone autograft in order to fill the residual bone defect. Six months after the treatment, clinical and radiographic signs of periodontal regeneration were evidenced. PMID- 7782985 TI - Guided tissue regeneration in severe periodontal defects in anterior teeth. Case reports. AB - Four consecutive chronic, severe periodontal bone defects in anterior teeth were treated by guided tissue regeneration, using a polytetrafluoroethylene periodontal membrane. The root surface was not specifically conditioned, and osseous grafts were not used. However the membrane was manipulated so that space under it was maintained. This was accomplished by painting the outer surface of the membrane with butyl-cyanoacrylate, so that it became rigid. The membranes were removed after 4 weeks and a bone-like tissue was found in all cases. The clinical results suggest that there was a relationship between the amount and quality of the new tissue and the volumetric characteristics of the available space. PMID- 7782986 TI - Post-rhizotomy periodontal atrophy. AB - This report details the experience of two people who suffered a unique type of periodontal atrophy following trigeminal sensory rhizotomy. The cause is unknown but it may be the result of unintentional self-mutilation. PMID- 7782987 TI - Successful bone fill in late peri-implant defects using guided tissue regeneration. A short communication. AB - Severe loss of peri-implant supporting bone traditionally leads to the removal of the affected implant, but this may not be necessary in all cases. This paper presents a novel treatment approach aimed at the successful regeneration of bone lost to peri-implantitis using guided tissue regeneration (GTR). Four years after implant placement two patients presented with severe peri-implant tissue breakdown. Clinical signs of disease included bleeding on probing, suppuration, increased probeable pocket depth (4 to 9 mm) and a decreased level of clinical attachment (2 to 10 mm). Radiographic analysis revealed 2.6 to 7.1 mm loss of supporting bone. Treatment of these lesions included raising flaps, wound debridement, and rinsing with sterile saline and 0.2% chlorhexidine digluconate. Subsequently, ePTFE membranes were adapted around the necks of the implants and the flaps sutured around the necks of the implants, allowing for transmucosal healing. Both patients were placed on a 10-day antibiotic regimen and instructed to rinse twice daily with a 0.12% chlorhexidine solution. They were reevaluated every 3 weeks at which time professional plaque control was performed. After 4 1/2 and 6 1/2 months, respectively, the membranes required removal due to infection. The radiographic analysis 1 year after membrane removal revealed 1.5 to 3.6 mm of bone gain. As a result of regenerative therapy the implants in both these patients were successfully maintained. It can be concluded that implants with severe loss of bone resulting from peri-implantitis need not always be extracted. A potential approach for the treatment of peri-implant bone destruction is GTR therapy using strict attention to good antimicrobial therapy. PMID- 7782988 TI - Re: Periodontal disease in non-insulin dependent diabetes (NIDDM). The effect of age and time since diagnosis (J Periodontal; 1994; 65: 991-995) PMID- 7782989 TI - Re: Gingival recession: intra-oral distribution and associated factors (J Periodontal 1994; 65: 864-871) PMID- 7782990 TI - Developmental truths in memories of childhood and adolescence. AB - This study of age-related changes in memories of personally important encounters showed "developmental truths," that is, patterns that converged with prior developmental theories and research. Participants were 47 males and 48 females in their early 20s. An average of 16 memories were collected from each person during an intensive personal interview. Memories were coded for age at the time of the episode, the identity of the other person with whom the study participant was interacting, what the participant wanted from the other person, and the outcome. As expected, memories of encounters with parents and about wanting help prevailed for childhood, whereas memories of encounters with close friends and about wanting intimacy prevailed by mid-adolescence. Memories about wanting to help others were sparse for this young-adult sample, but, like needs for intimacy, increased with age. Although patterns for males tended to be more dramatic than patterns for females, this trend appeared more attributable to actual developmental differences in social dynamics than to differences in the degree to which current concerns intruded into the memory process. The advantages of personally salient, event-specific retrospective reports for understanding personality development and change are discussed. PMID- 7782991 TI - Life after trauma: personality and daily life experiences of traumatized people. AB - In this study, we explored differences in personality and daily life experiences of traumatized (n = 26) versus nontraumatized (n = 30) college students. Study participants completed a variety of personality measures as well as a 28-day experience sampling study assessing daily activities, emotions, and physical health. Although not differing on general demographics, traumatized individuals reported more trait anxiety and lower self-esteem than nontraumatized individuals. They scored higher on Neuroticism, were more introverted, and were less emotionally stable than nontraumatized participants. Traumatized individuals also reported more cognitive disturbances, emotional blunting, and interpersonal withdrawal. They did not report being more depressed, but did endorse cognitive styles associated with heightened risk for depression. Earlier age of trauma was associated with more pathological outcomes: lower self-esteem and psychological well-being, more anxiety, more pessimism, and emotional constriction of positive mood. We compare this symptom profile to that of posttraumatic stress disorder. PMID- 7782992 TI - Extraversion: a "hidden" personality factor in coping? AB - Recent evidence suggests a larger role for personality determinants of the coping response than has been traditionally held. In the two studies presented here, we examined the influence of personality on the use of social support and other coping strategies in samples of undergraduate students. The first study surveyed a range of coping responses to naturally occurring stressors and found that Extraversion was related to social support seeking, optimism (identified as germane to coping in prior research) was related to problem solving, and both dispositions were negatively related to avoidance. The second study used an experimental approach and multiple personality measures to correct for possible methodological problems in the first. Extraversion again proved to be associated with help seeking; moreover, this relationship accounted for that of another disposition, self-esteem--a construct considered crucial in the literature. The utility of personality variables, particularly Extraversion, in predicting and explaining the choice of a coping strategy is discussed. PMID- 7782993 TI - Personality change in Parkinson's disease patients: chronic disease and aging. AB - Parkinson's disease patients (N = 41, mean age = 65 years) were described by themselves and their spouses as they were presently and before their illness using the Adjective Check List. Equivalent self- and spouse descriptions were obtained from the members of a matched community sample (N = 96). Descriptions of patients and their spouses converged, both reporting sharp, pervasive (e.g., on all of the Big Five dimensions), and uniformly negative change in personality. Similar, but much less marked change was found in the community sample. The data as a set suggest that the reported changes in the patients were veridical and that their magnitude was primarily the result of the disease rather than aging. Evidence of continuities in personality (for example, differential stability) was also noted. We argued that the illness accelerated and intensified changes normally expected in later life. PMID- 7782994 TI - The conflicted individual: personality-based and domain-specific antecedents of ambivalent social attitudes. AB - Historically, attitude theory and research has assumed that attitudes are largely unconflicted and unidimensional summary statements of feelings and beliefs. More recent work has reexamined this assumption (Thompson, Zanna, & Griffin, in press). The present article details two studies that continue to investigate this notion, examining antecedent variables assumed important in the genesis of attitudinal ambivalence. The first study focuses upon personality-based factors such as individuals' Need for Cognition (NFC) and Personal Fear of Invalidity (PFI) (a heightened concern with error). The pattern of results was consistent with our predictions: High NFC was associated with less ambivalence and high PFI was associated with greater ambivalence. The second study investigated a domain specific antecedent. It was predicted that higher involvement would reduce the level of ambivalence experienced. Further, involvement was expected to moderate the effect of the personality-based antecedents. Again, results confirmed our hypotheses. High NFC was associated with less ambivalence, especially under conditions of high involvement with the issues. Conversely, high PFI individuals who were highly involved with these issues experienced more ambivalence. These results are discussed in terms of their implications for attitude theory. PMID- 7782995 TI - On the nature of embarrassability: shyness, social evaluation, and social skill. AB - In this study, the correlates of embarrassability, or chronic susceptibility to embarrassment, were examined. Competing theoretical models suggest either that embarrassable people should be especially concerned about others' evaluations of them or that they should lack social skills. Further, shyness and embarrassment are typically considered to be closely related states. To test these propositions, 310 participants provided extensive self-reports of social skill, fear of negative evaluation, self-esteem, self-consciousness, and negative affectivity. Regression and factor analyses indicated that, compared to those of low embarrassability, highly embarrassable people are particularly concerned with the normative appropriateness of behavior and are more motivated to avoid rejection from others. In contrast, shyness was best predicted by low social self confidence and low social skill. The data best support a social-evaluation model of embarrassment and argue that embarrassability is linked to the appropriateness of social behavior, and shyness to its effectiveness. PMID- 7782996 TI - Synthetic polymers as materials for artificial vitreous body: review and recent advances. AB - In spite of a century of recorded attempts to replace the vitreous body of the eye with a foreign material, there is no permanent substitute currently available, and the success of some materials as temporary substitutes is still very limited. Among the large number of materials proposed or tested as vitreous substitutes, synthetic polymers have been episodically considered during the past four decades. This article will review these attempts, their outcomes, and recent progress in this field. There were only seven synthetic polymers and a few semisynthetic polymers (modified biopolymers) so far proposed or tested as vitreous substitutes. It appears that probably a synthetic hydrogel with very high water content would eventually be the material of choice for a permanent vitreous substitute, but the ideal material has not yet been found. PMID- 7782997 TI - Studies on the standardization of cytotoxicity tests and new standard reference materials useful for evaluating the safety of biomaterials. AB - Standard reference materials (SRM) made of polyurethane films containing various amounts of cytotoxic compounds such as zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) are proposed. The cytotoxicity indices of five dithiocarbamates and the SRM films obtained by colony assay were compared with those by published standards, i.e., neutral red assay (NF S 90-702), agar diffusion assay (USP XXII), and millipore filter diffusion assay (DIN-V 13 930). Among them, colony assay using 3 cell lines of Balb 3T3, L929 and V79 was found to be most sensitive. The extraction method and direct contact method were proposed as two test methods of colony assay. In the former, culture media after incubation with test materials were used as test solution, and in the latter, cells were directly cultured on test materials. The extraction method gave a linear relationship between the cytotoxic potentials of the SRM and its concentration of ZDEC or ZDBC. The cytotoxic potentials of the SRM correlated well with the thickness of inflammatory layer in rabbit muscle implantation tests of the SRM. The direct contact method was found to be useful to detect weak cytotoxicity because of its high sensitivity. Based on these data, we propose the colony assay and the two kinds of new SRMs as Japanese standard test method for evaluating the cytotoxicity of biomaterials. PMID- 7782998 TI - Pulsatile blood flow from impeller pump: a dream has come true. AB - For decades many investigations have been made on producing a pulsatile blood flow with an impeller pump. It has been foiled because of excessive hemolysis. Other investigators foretold that a pulsatile centrifugal pump is impossible in the near future, without increasing the complexity of the system remarkably. The author has presevered in this study and made progress steadily. An axial pulsatile impeller pump with constant-rotating speed was developed, in which the impeller reciprocates along its axis while rotates. Meanwhile, a pulsatile implantable impeller centrifugal pump is now in animal surviving experimental stage. The pulsatility of the blood flow is achieved by changing the rotating speed of the impeller periodically, via introducing a square wave form voltage into the motor coil. The hemodynamic and physiological superiorities to both nonpulsatile impeller pump and diaphragm pump were demonstrated. The hematological and biochemical data indicated low hemolysis and thrombogenesis, low renal and heptic dysfunction. Furthermore, a pulsatile implantable impeller total heart has completed its acute biventricular assist animal experiments. This is an almost unique total heart at the present, it is driven by a single motor, the left and right pumps eject the blood simultaneously, and the volume equilibrium of both pumps is achieved naturally. The dream of producing a pulsatile blood flow with an impeller pump has come true. Doubtlessly, an impeller heart with simplicity, pulsatility, implantability, compatibility and reliability, will be a viable alternative to diaphragm heart, really. PMID- 7782999 TI - Highly publicized medical device failures have made headlines in the lay press. PMID- 7783000 TI - Simultaneous raw starch hydrolysis and ethanol fermentation by glucoamylase from Rhizoctonia solani and Saccharomyces cerevisiae. AB - Crude glucoamylase preparation from Rhizoctonia solani was used to saccharify raw and cooked starch. Various concentrations of potato starch and wheat flour from 10-40%, w/v were used for mashing but 30% was found to be the optimal and economical. The saccharified mash yielded 5.89%, v/v ethanol in a simultaneous saccharification and fermentation process using a yeast strain Saccharomyces cerevisiae (SC-39) at 35 degrees C for 4 days. Removal of inhibitory substances from the fermenting broth through dialysis caused considerable increase in ethanol production. PMID- 7783001 TI - Microbiological survey of a South African poultry processing plant. AB - Bacterial populations associated with poultry processing were determined on neck skin samples, equipment surfaces and environmental samples by replicate surveys. Aerobic plate counts, Enterobacteriaceae counts, Enterobacteriaceae counts and Pseudomonas counts were performed by standard procedures and the prevalence of Listeria, presumptive Salmonella and Staphylococcus aureus determined. Statistically significant (P < 0.05) increases in counts of all types of bacteria were obtained on product samples as a result of processing. Although bacterial counts on neck skin samples decreased by 0.3 to 0.4 log CFU g-1 after spray washing of carcasses, subsequent spinchilling and packaging of whole carcasses resulted in 0.7 to 1.2 log CFU g-1 increases. Bacterial numbers on equipment surfaces, however, decreased significantly from the "dirty" to the "clean" areas of the abattoir. Transport cages, "rubber fingers", defeathering curtains, shackles and conveyor belts repeatedly showed aerobic plate counts in excess of 5.0 log CFU 25 cm-2. Aerobic plate counts of scald tank and spinchiller water were 2 log CFU ml-1 higher than those of potable water samples. Bacterial numbers of the air in the "dirty" area were higher than those of the "clean" area. Listeria, presumptive Salmonella and Staphylococcus aureus were isolated from 27.6, 51.7 and 24.1% of all product samples, respectively, and Listeria and Staphylococcus aureus were also isolated from selected equipment surfaces. PMID- 7783002 TI - Phenol and cresol metabolism in Bacillus pumilus isolated from contaminated groundwater. AB - From an aquifier contaminated with phenolic compounds seven bacterial strains able to grow on phenol and several mono- and disubstituted alkylphenols as sole source of carbon and energy were isolated. Five isolates belong to the genus Pseudomonas, two to the genus Bacillus. The isolate most active in utilization of the applied xenobiotics was identified as Bacillus pumilus and used for the investigation of the degradation pathways in liquid cultures. Cells of this strain precultured on phenol were able to utilize para-cresol as sole carbon source via the oxidation of the methylsubstituent and intradiol ring cleavage of the resulting protocatechuic acid, whereas an intradiol ring fission of the intermediate 4-methylcatechol led to 4-methylmuconolactone as dead end-product. Cells precultured on meta- and ortho-cresol were able to utilize the respective compounds as sole carbon sources via 3-methylcatechol, which induced the following extradiol ring fission pathway. Cells precultured on phenol were able to cooxidize meta- as well as ortho-cresol to 3-methylcatechol, which was cleaved via an intradiol ring fission, finally leading to the dead end-product 2 methylmuconolactone. PMID- 7783003 TI - Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. AB - Oral submucous fibrosis (OSF) is a high risk precancerous condition, predominantly affecting Indians. Consumption of chilli was hypothesized as an etiologic factor on the basis of ecological observations and a solitary animal experimental study. Subsequent epidemiologic studies that included case-series reports, large cross-sectional surveys, case-control studies, cohort and intervention studies have identified areca nut as the major etiologic agent. Tissue-culture studies involving human fibroblasts, areca nut extracts and areca nut alkaloids supported this etiologic hypothesis by showing fibroblastic proliferation and increased collagen formation. Currently, the role of genetic susceptibility and that of autoimmunity are receiving attention. The influence of nutritional factors, if any, remains unclear. PMID- 7783004 TI - Enamel microhardness and histological features of composite enamel pearls of different size. AB - The aim of this study was to investigate the enamel microhardness and the histological features of eight enamel pearls of various size. The microhardness of the pearl enamel ranged from 272.4 to 407.2 Vickers microhardness values (VMV) and resembled that of the enamel of the carrier teeth (277.1-424.3). A histological resemblance between the tissues of the enamel pearls and those of the carrier teeth was also found. The resemblance was more pronounced in larger pearls, which showed a variability of the enamel microhardness and structure in the occlusal-cervical direction typical of the tooth crown. Large pearls also exhibited a root and a pulp. Some histological features of the enamel pearls were probably caused by pressures exerted on the developing pearl by its surroundings. It is suggested that the histogenesis of small and large pearls is based on the ability of the developing root of the carrier tooth to behave in part as a new tooth germ. PMID- 7783005 TI - Epithelial cell kinetics in oral leukoplakia. AB - Cell proliferation in oral leukoplakia has been studied by estimating the number of cells in the S phase using in vitro 3H thymidine labelling. The labelling index was found to be increased 1.77 fold in leukoplakias compared to the clinically normal control sites (P < 0.005). This rise in labelling index was found to be related to an increase in the proportion of the cells in the basal cell layer engaged in cell production. Both leukoplakia and the control specimens showed epithelial atypia, although in the latter samples this was mild yet suggestive of a possible field change in the oral epithelium of a small group of tobacco users. A significant positive correlation was found between the epithelial atypia score and the labelling index. This raises the possibility of using the labelling index as an objective prognostic marker in assessing potential malignancy in oral leukoplakia lesions. PMID- 7783006 TI - Immunohistochemical characterisation of odontogenic cysts with mesenchymal and myofilament markers. AB - The aim of the present investigation was to analyse the fibroblast phenotype in the main groups of odontogenic cysts. We have examined the muscle differentiation markers alpha-smooth muscle actin (ASMA) and desmin and the presence of vimentin using immunocytochemistry. Fibroblasts of other cyst types, hyperplastic fibrous lesions, and from several normal sites were used as controls. All fibroblasts stained for vimentin, but a variable proportion of cyst wall fibroblasts were also positive for the antibody to ASMA. Their distribution was not random and two positive zones could be distinguished, an inner subepithelial layer and an outer region adjacent to the bone-facing surface. This staining pattern was observed for all the types of odontogenic cysts studied, although the subepithelial staining was more frequent in the presence of an inflammatory infiltrate. The contractile nature of these cells was supported by their ultrastructural appearance. Some non-odontogenic cysts showed subepithelial fibroblasts strongly labelled with ASMA; in the control tissues ASMA was negative except for pericytes and some groups of cells in supracrestal gingiva. These results demonstrate a distinct cell population with a myofibroblast phenotype in the odontogenic cyst wall and with a distribution which may enable them to contribute to wall elasticity constraining cyst expansion. Their presence in all types of odontogenic cyst studied would suggest that myofibroblast formation is independent of the pattern of cyst growth. PMID- 7783008 TI - Feline inductive odontogenic tumor (inductive fibroameloblastoma)--a tumor unique to cats. AB - The inductive fibroameloblastoma is a rare odontogenic tumor that occurs in young cats of either sex, predominantly in the anterior maxilla. This article critically reviews the previously published examples with emphasis on microscopic features, relationship to ameloblastic fibroma, and biologic behavior; an additional example is described. This tumor differs microscopically from human ameloblastic fibromas in that it is not well-circumscribed but rather originates multifocally within the supporting connective tissue as characteristic, spherical condensations of fibroblastic connective tissue (ectomesenchyme) associated with islands of odontogenic epithelium. Its biologic behavior requires further study but the tumor apparently is unique to cats and is distinct from human ameloblastic fibroma. Consequently, feline inductive odontogenic tumor is suggested as being a more appropriate designation than inductive fibroameloblastoma. PMID- 7783007 TI - Liposarcomas of the oral tissues: a clinicopathologic study of four tumors. AB - Liposarcomas of the oral tissues are rare. There have been 28 previously reported in the literature. A clinicopathologic study of 4 patients with liposarcoma involving the oral tissues is presented--one in the tongue, one in the palate, and two in the submandibular space. Two of the tumors were myxoid, one was of well-differentiated type and one was of pleomorphic type. Three of the lesions were diagnosed clinically as benign. The most important lesson to be learned from the histopathology is the positive identification of atypical lipoblasts. Follow up data indicate that prognosis generally corresponds to the tumor type. The patients with myxoid and well-differentiated liposarcoma remain alive and with no evidence of disease. The patient who died of tumor had a pleomorphic liposarcoma. Treatment of these lesions should consist of wide surgical excision and consideration of adjunctive or palliative radiotherapy. PMID- 7783009 TI - Pterygoid muscle function in excursive jaw movements: a clinical report. PMID- 7783011 TI - A postfabrication technique for identification of prosthetic devices. PMID- 7783010 TI - Ability of various impression materials to produce duplicate dies from successive impressions. AB - This in vitro study evaluated the ability of five different impression techniques to make duplicate dies of two different types of tooth preparation. One mandibular second premolar Ivorine tooth was prepared for a complete crown and one for an onlay. A master impression was made of each tooth preparation with the use of five impression techniques for a total of 10 master impressions, and a master die was made from each of these impressions. Castings were made on these master dies, and the fit of each casting was verified on the respective Ivorine tooth. Marginal openings of the castings on the master dies were recorded under magnification at four predetermined points. Five successive impressions, with the use of each impression material, were then made of each tooth preparation for a total of 50 test impressions, and 50 test dies were made from these impressions. The fit of the respective casting was evaluated under magnification for each test die at the four predetermined points, and marginal openings were recorded. Differences between the marginal discrepancies of the casting on the master die and on the test die were tabulated and the results were statistically analyzed. Results indicated that none of the impression materials was capable of producing exact replicas. Polysulfide rubber performed significantly better than two materials for the production of duplicate dies with the complete crown preparation; and polyvinyl siloxane used with a putty-light body, single-stage technique produced mean marginal discrepancies that were significantly greater than the other four techniques when used for the onlay preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783012 TI - Retention and stability of the maxillary denture during function. AB - The objectives of this study were to provide a quantitative account of the extent to which the maxillary complete denture moves during function (chewing, swallowing, and speech production) and to determine whether differences in movement occur as a function of denture fit. A total of 24 patients were studied, 12 with poorly fitting dentures and 12 with well-fitting dentures. Denture movements were measured with a Myotronics kinesiograph that tracked the movements of a small magnet attached to the inferior surface of the denture. Results indicated that denture movement was greatest for the two chewing activities; varied extensively from individual to individual; and that there were no statistically significant overall movement effects as a function of fit. It was concluded that all maxillary dentures are subject to movements in all directions, but that the degree of movement is related more to the individual denture wearer than it is to the fit of the denture. PMID- 7783013 TI - Accuracy of freely adapted resin record bases. AB - Forty autopolymerizing resin record bases were made; 10 bases were adapted by finger pressure on tray resin material dough, 10 bases by sprinkling orthodontic resin, and 10 of repair material by either of the two previous techniques. Stone casts and acrylic resin bases were sectioned at canine, premolar, and molar coronal planes. Width of the gap between base and cast and the thickness of the base were measured at the buccal sulcus, ridge crest, lateral palatal slope, and palatal midpoint. Measurements were made through the eyepiece of a microhardness tester. Statistical analysis of 760 pairs of measurements revealed that (1) sprinkled bases fit better than finger-adapted dough bases; (2) specifically formulated materials fit better than repair material with either technique; (3) gap widths differed at different areas of the same base; and (4) gap width was not related to base thickness at any point. PMID- 7783014 TI - Prospective clinical evaluation of mandibular implant overdentures: Part I- Retention, stability, and tissue response. AB - Seventeen subjects with preexisting conventional complete dentures were evaluated in this prospective clinical study. Two implants were placed bilaterally in the anterior mandible. In a crossover experimental design, the conventional dentures were modified, and the retention, stability, and tissue response for conventional dentures were compared with implant overdentures that had O-ring and magnet overdenture attachments for all subjects. The study indicated statistical superiority of the implant overdenture to the conventional denture. The O-ring attachment proved significantly better than the magnet attachment for retention and stability. The soft tissue response showed a slight but significant improvement with implant overdenture therapy. PMID- 7783015 TI - Prospective clinical evaluation of mandibular implant overdentures: Part II- Patient satisfaction and preference. AB - In a crossover experimental design, a prospective clinical study was performed with 17 subjects with existing complete dentures. After data collection, two implants were placed bilaterally in the anterior mandible. Conventional dentures were modified into implant overdentures by use of O-ring and magnet attachments. Each attachment was maintained with each subject for 6 months. Subjects responded to patient satisfaction and preference questionnaires about the conventional denture and each attachment. Subjects were satisfied with both attachment overdentures but showed a strong preference for the O-ring. Both attachments resulted in a significant increase in patient satisfaction when compared with the conventional denture. PMID- 7783016 TI - A two-stage impression technique for custom facial prostheses. AB - A two-stage impression technique that uses polyvinyl siloxane and irreversible hydrocolloid in a custom impression tray is described. The technique records the tissues to be contacted by the facial prosthesis with minimal distortion with the patient in an upright position and facial musculature at rest. The procedure is simple, accurate, and it eliminates some of the shortcomings of other techniques. PMID- 7783017 TI - The ultrasonic value of local muscle hypertrophy in patients with temporomandibular joint disorders. AB - Muscle pain and tenderness on palpation are two common symptoms in patients with temporomandibular joint disorders. Examination of the masticatory muscles is largely restricted to the use of electromyography. The technique of ultrasonography in the diagnosis of muscle hypertrophy in patients with temporomandibular joint disorders was investigated. The results of the study indicate that ultrasonography may be beneficial to locate affected muscles that do not exhibit symptoms of tenderness on palpation and thereby give hints for treatment planning. PMID- 7783018 TI - Tensile fatigue of 4-META cement bonding three base metal alloys to enamel and comparison to other resin cements. AB - The tensile median fatigue limits and fracture mode of 4-META cement were evaluated after bonding Ni-Cr, Ni-Cr-Be, and Co-Cr alloys to enamel. Alloy surfaces, 6 mm in diameter, were grit blasted with 50 microns Al2O3 and cemented to etched bovine enamel under a 2 kg load. Samples were cycled in tension to failure or 10(6) cycles at 5 Hz in Ringer's solution at 37 degrees C. Two-point strategy was used to determine median fatigue limits (S50). Fracture modes were evaluated by SEM on samples failing before 10(6) cycles. Results indicated differences between all sample groups where S50 (Ni-Cr-Be) > S50 (Co-Cr) > S50 (Ni-Cr). Failure analysis revealed mixed cohesive fractures near both interfaces with small areas of delamination within the cement. Comparison to reported median fatigue limits of two commercially available cements were discussed. PMID- 7783021 TI - Protection of glass ionomer cements during the setting reaction. PMID- 7783020 TI - Effect of dimension of luting space and luting composite on marginal adaptation of a class II ceramic inlay. AB - This study evaluated the in vitro marginal quality at the interproximal cervical margin of class II Cerec restorations. Marginal quality was evaluated separately by (1) SEM analysis before and after simultaneous thermocycling and mechanical loading for the integrity of the restoration surface and (2) dye penetration after thermocycling and mechanical loading to evaluate the strength of the bond within the depth of the cavity. The results reveal that marginal integrity is influenced by the width of the luting space and the luting composite. With a luting space of 100 microns, marginal quality with as little as 3% to 14% loss of adhesion can be obtained. Luting spaces greater than 100 microns can partially be compensated by the luting composite. For Cerec inlays, highly filled luting composites with a high viscosity are recommended. PMID- 7783019 TI - Effect of unfilled resins and a silane primer on bonding between layers of a light-activated composite resin veneering material. AB - This investigation evaluated the effect of unfilled resins and a silane primer on bonding between layers of a urethane-based composite resin veneering material. Shear bond strengths between the layers were determined with a two-liquid silane primer and three unfilled resin bonding agents. The silane primers and unfilled resins enhanced the bond between layers of the veneering material. Durability of the bond, however, was influenced by the composition of the bonding agent. Among the systems investigated, combined use of the silane primer with triethyleneglycol dimethacrylate-based unfilled resin exhibited durable and consistent bond strength. PMID- 7783022 TI - Development of an outpatient perioperative care record. AB - Since the 1970s outpatient surgery has become increasingly popular as a mechanism for reducing hospitalizations and allowing patients to recuperate in their own homes. Advanced nursing care, improved surgical procedures, and modern pharmaceuticals and anesthetic techniques increase the rate and quality of patient recovery and allow the patient to enter the hospital, undergo surgery, and be discharged in the same day. It is now estimated that more than 40% of all surgeries are being performed in the outpatient setting. The rapid turn-around time for outpatient surgeries creates new challenges for nurses as well as patients and their families. Documentation of surgical procedures and nursing care is essential for communicating with other providers and for establishing a legal document that can be used to evaluate the quality of services delivered. Yet the time available for record keeping is greatly reduced. New charting procedures are needed to decrease redundancy and enhance the structural efficiency of perioperative records. This article describes a method of streamlining perioperative outpatient surgery records. The use of nursing diagnoses is incorporated into a documentation system that uses checklists, flowsheets, and charting by exception. PMID- 7783023 TI - Mastering the weaning process in the postanesthesia care unit. AB - Most PACUs are accustomed to rapidly weaning patients who arrive on mechanical ventilators. However, as the acuity of patients in the PACU continues to increase, the ability to quickly wean patients to extubation is becoming less possible. The difficult-to-wean patient population is requiring the PACU nurse to become more astute in assessing and planning the weaning process. A collaborative approach can facilitate the successful weaning of a patient from the ventilator. PMID- 7783024 TI - Rewarming hypothermic postanesthesia patients: a comparison between a water coil warming blanket and a forced-air warming blanket. AB - The warming effects of a Blanketrol water coil-heated hypothermia blanket and a Bair Hugger forced-warm air warming blanket were compared. Thirty-two patients admitted to the PACU with temperatures 34.4 degrees C (94 degrees F) or lower were assigned to treatment with the Blanketrol (Cincinnati Sub-Zero Products, Cincinnati, OH) or the Bair Hugger (Augustine Medical, Eden Prairie, MN) in alternating fashion, and treatment continued until the patients' temperatures reached 36.1 degrees C (97 degrees F). Every half hour each patient's temperature was measured using a tympanic temperature device and recorded on the data collection sheet. Analysis of the findings showed that the forced-air warming blanket warmed patients to 36.1 degrees C (97 degrees F) or higher significantly faster than the water coil-heated blanket (P < .001). PMID- 7783025 TI - Identification of potential problems for elderly outpatients after preoperative medication: a case study. AB - Meperidine and promethazine are preoperative medications ordered frequently for outpatient and inpatient surgical procedures in this facility. Although all medications have the potential to cause adverse reactions, the case studies presented in this article suggest a relationship between the use of one or both of these drugs and the cancellation of surgery, ie, two surgical procedures were cancelled because of the patients' behavior after administration of preoperative medication. Nurses are advised of the potential for reactions, especially in the elderly patient. Further examination of this topic is essential to prevent other episodes of adverse drug reaction or cancellation of surgical procedure and to add to the current knowledge base of effective preoperative medications. PMID- 7783026 TI - Taking control: an approach to problem solving. PMID- 7783027 TI - Reading research critically: results--Part 1. AB - Nurses in PACUS as well as other areas of nursing are increasingly being asked to incorporate research into their clinical practices. Unfortunately, many nurses have limited formal education in research and are not adequately prepared to critically analyze the quality of the research they are reading. This is especially true when it comes to the statistical analysis section of the published research report. This article lays the foundation for understanding the statistical analysis most commonly seen in results sections of research publications in nursing journals. PMID- 7783028 TI - Tomorrow's workplace: no jobs ... just work to be done. AB - The workplace of the future will be less structured, and roles will be less specific. As teams and teamwork become the way to get the work done, those who have relied on a job description to direct what they do will face a real challenge. As this shift in thinking moves into the health care setting, there is fear and confusion on the part of both managers and staff. By working together, managers and staff can build trust and a new sense of security even in an uncertain future. PMID- 7783029 TI - Is your personal breathing zone healthy or hazardous? AB - Numerous studies over several decades have indicated that exposure to ambient anesthetic gases place health care providers and their families at risk of serious health problems. As a result, scavenging systems are used in virtually every Operating Room. But the risk for thousands of caregivers has not been given adequate attention. This article discusses the results of several studies and their implications for providers of postanesthesia care. PMID- 7783030 TI - The habit of synergy. PMID- 7783032 TI - Caregiver burden: grandmothers raising their high risk grandchildren. AB - 1. The term caregiver burden currently describes the physical, psychological, emotional, social, and financial problems that can be experienced by family members who are caregivers. 2. The health, emotional and psychosocial well being of the grandchild (care recipient) directly affects the grandmother caregiver's health, emotional, and psychosocial well being. 3. The nursing profession is in an ideal position to identify effective interventions to reduce the stress grandmothers feel. PMID- 7783033 TI - Protecting our children: where have we gone and where should we go from here? AB - 1. There are 3 million cases of child abuse reported each year. Three million grandparents in this country rear their grandchildren because the parents are not fit enough or competent enough to do so. 2. Each year, 500,000 American children give birth. 3. One way to stop child abuse and neglect is to provide children with constitutional rights. PMID- 7783031 TI - Biology of memory and childhood trauma. AB - Examples have been presented of children's behaviors that demonstrate the trauma learning pattern of re-enactment, repetition, and displacement. They become persistent parts of the symptom complex of PTSD. The encapsulation phase occurs when the trauma event occurs and symptoms present themselves, but the events as yet are undisclosed. The trauma-specific behavior patterns, the general hyper arousal symptoms, and the avoidant, numbing symptoms persist; the emerging disruptive behaviors are not linked to the traumatic event and reactions to the trauma. The response of the child's social and interpersonal context to the internalizing or externalizing behaviors post-trauma, continue shaping the internal cognitive schema of the child. When the child is unable to link ongoing, self-defeating, disruptive behavior to trauma experience, the underlying fear persists. This interferes with the child's ability to modulate emotions either through altering the persistence of refractory, self-limiting cognitive schema or the inability to use new experience to develop and grow. The flexibility of children to discriminate new information may be lost; the children are either numb to new information or hyperalert and perceive danger. Issues for treatment include children's distress over memories of the trauma and the lack of capacity to learn and develop from new interpersonal experiences. It has been our experience that nurses first must help the child relearn flexibility through self observation, the element of self-soothing and calming behaviors, processing of new information, and strengthening of social relationships. With new and strengthened personal resources, the child then is able to begin to process the traumatic memories. PMID- 7783034 TI - Incorporating psychiatric rehabilitation principles into mental health nursing. An opportunity to develop a full partnership among nurses, consumers, and families. AB - 1. Once people with mental illness are perceived as people with disabilities, the field of physical rehabilitation can be used as a metaphor for psychiatric (or psychosocial) rehabilitation. 2. A rehabilitation approach emphasizes the development of skills and sources of support necessary for successful living, learning, and working in the community. 3. The essential components of psychiatric rehabilitation technology clearly are defined practitioner skills and the underlying knowledge about how to use the skills most effectively. PMID- 7783036 TI - Logical responses to youth who run away from home: implications for psychiatric mental health nursing. AB - 1. Runaway youths do not fit into a typical profile; they are adolescents of every race, ethnic group, and religious orientation; they are representative of every socioeconomic status and geographic location in America. 2. Psychosocial events including physical and sexual abuse are common antecedents to runaway behaviors. 3. Implications for psychiatric mental health nursing practice include working with community programs focused on reducing runaway episodes; implementing preventive measures focused on strengthening parenting and problem solving skills for reducing conflict with families with adolescent children; and promoting responsible sexuality through adequate and responsible sex education and counseling. PMID- 7783035 TI - Constant observation: implications for nursing practice. AB - 1. Constant observation is an increased level of observation and supervision in which continuous one-to-one monitoring techniques are utilized to assure the safety and well-being of an individual patient or others in the patient care environment. 2. Individuals who provide constant observation vary widely among health care facilities; but ultimately are the responsibility of the registered nurse. There are many areas that must be addressed by institutions when considering the use or implementation of constant observation. These include: measuring the associated costs, risk management, role development, orientation of employees, and performance evaluation. 3. The changing health care environment and public concern over the quality of health care and risk management require nursing administrators to consider risk-benefit and cost-benefit analyses related to constant observation. There is continued need for protocol and policy development, as well as for guidelines and orientation of staff regarding constant observation. PMID- 7783037 TI - [MRI of the rotator cuff: evaluation of a new symptomatologic classification]. AB - The different classifications use for the rotator cuff pathology seem to be incomplete. We propose a new classification with many advantages: 1) Differentiate the tendinopathy between less serious (grade 2A) and serious (grade 2B). 2) Recognize the intra-tendinous cleavage of the infra-spinatus associated with complete tear of the supra-spinatus. 3) Differentiate partial and complete tears of the supra-spinatus. We established this classification after a retrospective study of 42 patients operated on for a rotator cuff pathology. Every case had had a preoperative MRI. This classification is simple, reliable, especially for the associated intra tendinous cleavage. PMID- 7783038 TI - [Diagnosis of non-palpable breast lesions: contribution of cytological punctures after stereotaxic localization]. AB - The authors reviewed the accuracy of stereotaxic fine-needle aspiration cytology. Two hundred-twenty-eight lesions were studied: 103 benign lesions, 125 cancers. Inadequate sample was obtained in 26% of cases. None of the cytology reports were false-positive, whereas 77% of the suspect cytologic reports were malignant on histology. In strongly suspicious lesions at mammography, the decision to perform surgical biopsy should not be postponed as false negative cytologic findings (7 cases) are possible. In patients with a low suspicious lesion, cytology found six cancers. The benign-to-malignant ratio of excisional biopsies of non palpables lesions should be reduced by stereotaxic fine-needle aspiration cytology. PMID- 7783039 TI - [Solid breast nodules: reliability of ultrasonographic and cytological studies]. AB - The authors evaluated the usefulness of US study and US guided fine-needle aspiration cytology (FNAC) in 144 solid breast lesions. US studies was performed with a 10-MHz transducer. Homogenous hypoechogenicity, elongation along the general orientation of the breast tissue plane, regular margins, and intensification of posterior echoes were considered as benign signs. US guided FNAC was performed when lesions were depicted at US. The smears were performed immediately by the cytologist who was present during the procedure. US signs and FNAC diagnoses were compared with surgical/core biopsy diagnoses or negative imaging follow-up. The sensitivity of US was 93%, specificity 75%, accuracy 81%. Among 41 malignant lesions the cytologic findings were malignant (n = 26) or suspicious (n = 7) with 1 false positive and 2 false negative. Inadequate samplings were less frequent last year study (13.5%). The sensitivity of cytologic diagnosis was 94%, specificity 85%, and accuracy 88%. US study and FNAC could be helpful in evaluating solid breast lesions. A better accuracy may be obtained if FNAC is associated with core biopsy. PMID- 7783040 TI - [Imaging of severe forms of hematoma in the rectus abdominis under anticoagulants]. AB - AIM: To describe the US, CT and MRI pattern of the severe rectus sheath hematoma (RSH) complicating anticoagulant therapy. MATERIALS AND METHODS: CT scans were performed in thirteen patients (12 women, 1 man) aged from 53 to 90 (mean age, 74) with severe RSH. Five patients also underwent ultrasound examination and three MR examination. Nine patients (69%) were receiving subcutaneous injection of heparin, three (23%) oral anticoagulant therapy and one continuous IV infusion of heparin. Clinical diagnosis was reached in 6 cases. Excessive activity of anticoagulant therapy was noted in 4 cases. The location of the RSH, their densities and their signal were analysed. RESULTS: All the RSH were mostly developed in the lower third of the abdominal wall, had a large spreading into the Retzius space and compressed the bladder and/or the bowels. RSH were all hyperdense and in 8 cases (61%) a fluid-fluid level due to the hematocrit effect was noted. In one case, a retroperitoneal hematoma was discovered. The extension of the RSH was well delineated with MRI. The RSH showed itself with heterogeneous signal intensities with areas of high-signal-intensity on T1-weighted images. Fluid-fluid levels and a concentric ring sign were also noted. CONCLUSION: Older women with subcutaneous injection of heparin are especially prone to RSH even though there is no overall excessive activity of anticoagulant therapy. Clinical and biological diagnosis may be difficult. CT scan is the exam of choice to reach a precise and acute diagnosis of RSH. PMID- 7783041 TI - [Imaging of hepatic tuberculoma]. AB - We describe a case of localized macronodular tuberculosis of the liver, the so called hepatic tuberculoma. Liver US scan demonstrated an hypoechoic well delineated lesion of the left liver lobe. Liver CT scan demonstrated a hypodense lesion before and after contrast enhancement. Liver MR scan demonstrated a lesion hypointense to liver on T1-weighted images and isointense to liver on T2-weighted images. PMID- 7783042 TI - [Multilocular cyst of the kidney in a child. Value of MRI?]. AB - We report one case of multilocular cyst of the kidney in one year and three months female infant who underwent echography, computed tomography and MRI before surgery. MR image accurately reflect the morphology of the tumor: the capsule is hypointense on T1-weighted images, the septa show moderate enhancement with intravenous contrast. Varied intensities from fluid in the visualised locules presumably represent different concentration of proteins. MR imaging features are highly suggestive but non pathognomonic of the disease. Positive diagnosis always require histology. PMID- 7783043 TI - [Tuberculous tenosynovitis of the wrist: ultrasonographic diagnosis and contribution of MRI]. AB - Chronic tenosynovitis of the hand due to Mycobacterium tuberculosis has become rare. In the two cases presented here, the final diagnosis was obtained by isolation of the organism in the intercarpal fluid (1 case), or by a synovial biopsy (1 case). Ultrasonography showed a hypoechoic thickening of one or several tendon sheaths. MR enabled better differentiation between the thickening of the synovium itself and a fluid effusion. The criteria permitting to differentiate tuberculous from non-infectious tenosynovitis are: young age, male sex, specific epidemiological factors, elevated erythrocyte sedimentation rate, marked local swelling, association with other foci of tuberculosis, unusual exudation and synovial thickening, and association with osteitis. PMID- 7783045 TI - [MRI demonstration of soft tissue involvement in algodystrophy of the hip]. PMID- 7783044 TI - [False aneurysm of the abdominal aorta of hydatid origin]. AB - The rupture of hydatid cysts into the abdominal aorta is an exceptional and serious complication of the hydatid disease. We report a case of hydatid false aneurysm of the abdominal aorta, explored by US Doppler, C.T. and arteriography. PMID- 7783046 TI - [Immobilization and filtration for arteriography of the lower limbs]. PMID- 7783047 TI - [MRI aspect of Wernicke encephalopathy]. PMID- 7783048 TI - [Cleidocranial dysostosis]. PMID- 7783049 TI - [Radiology education in Quebec: an example to be followed?]. PMID- 7783050 TI - Soluble tumor necrosis factor receptors in arthritis. PMID- 7783051 TI - Activated gelatinase-B (MMP-9) and urokinase-type plasminogen activator in synovial fluids of patients with arthritis. Correlation with clinical and experimental variables of inflammation. AB - OBJECTIVE: To evaluate the occurrence of gelatinase-B (matrix metalloproteinase 9, MMP-9) in synovial fluids (SF) of patients with arthritis to investigate the possible role of this neutral MMP in joint destruction. METHODS: In paired (series I) and unpaired SF (series II) we examined the occurrence of gelatinase B, prostromelysin-1, and urokinase-type plasminogen activator (u-PA). RESULTS: In the paired SF a parallelism between the presence of activated gelatinase-B and the local arthritis activity scores of the knees was observed. Activated gelatinase-B correlated well with the presence of stromelysin-1 and u-PA, 2 enzymes probably involved in the activation process of gelatinase-B. In the 2nd series, activated gelatinase-B was found in 56 SF samples, whereas 82 samples did not exhibit activated gelatinase-B. The SF samples with the activated form of gelatinase-B showed a significantly higher ability to induce permeability changes in cultured monolayers of human endothelial cells, had more myeloperoxidase activity--secreted by infiltrated leukocytes--and had higher u-PA antigen concentrations, compared to SF samples without the activated form of gelatinase B. CONCLUSION: Our data suggest that the presence of gelatinase-B is a reflection of the inflammatory condition of the joints of patients with arthritis, and that the activation of gelatinase-B in the joints, which may occur in a u-PA/plasmin dependent and/or a stromelysin dependent way, contributes to the progression of arthritis. PMID- 7783052 TI - T cell receptor distribution in rheumatoid synovial follicles. AB - OBJECTIVE: In rheumatoid arthritis (RA) joint erosion is accompanied by T cell infiltration of the synovial tissue. The resulting T cell receptor (TCR) repertoire is a combination of antigen driven shaping, nonspecific selection by endothelial cell-T cell interactions, and cytokine mediated chemoattraction. Considering the conflicting results of molecular biology studies of the TCR repertoire in RA, we attempted to obtain new data to clarify the situation through microscopic distribution analysis of TCR beta chain diversity in synovium follicular CD4/CD8 subsets. METHODS: We used dual color fluorescence confocal microscopy with CD4/CD8 monoclonal antibodies (Mab) and a panel of new anti-V beta Mab. The analysis focussed on lymphocyte rich, follicle-like areas of synovial tissue from 4 patients with RA. RESULTS: The expression of individual TCR beta families varied between areas within the T cell follicles, and between patients. Normal absolute levels of some beta chains can be completely skewed towards one subset, indicating that overall TCR evaluation is insufficient. CONCLUSION: Confocal microscopy analysis of localized TCR diversity in RA synovium offers novel insight into overall V beta gene usage, which appears to be the accumulation of several localized microexpansions. PMID- 7783053 TI - Synthesis and degradation of hyaluronate by synovia from patients with rheumatoid arthritis. AB - OBJECTIVE: Hyaluronate degradation was analyzed in cultures of healthy tissue and tissue obtained from patients with rheumatoid arthritis. METHODS: Arthritic and healthy synovial tissues were incubated in culture with [3H]glucosamine. Labelled hyaluronate was extracted and its size determined by gel filtration. The production of low molecular weight hyaluronate was analyzed by pulse-chase experiments. Radical production was measured by a cytochrome C reduction assay. RESULTS: Healthy tissues and some arthritic tissues that did not contain significant amounts of granulocytes produced high molecular weight hyaluronate. In contrast, arthritic tissue infiltrated with granulocytes released low molecular weight hyaluronate. Pulse-chase experiments suggested that hyaluronate was degraded in these arthritic tissues. Exogenous hyaluronate was degraded only by intact tissue, but not by cells in culture obtained from synovial membranes of synovial fluids. Hyaluronate degradation was accompanied by massive oxygen radical production. Radical scavengers protected hyaluronate from degradation in synovial tissue. Some protection was achieved by superoxide and catalase or by methionine and complete protection by the iron chelators diethyltriaminepentacetic acid or deferoxamine mesylate. CONCLUSION: Degradation of hyaluronate in arthritic synovial tissue may be inhibited in tissue culture by radical scavengers. PMID- 7783054 TI - Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid of patients with rheumatoid arthritis, reactive arthritis and osteoarthritis. AB - OBJECTIVE: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases. METHODS: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables. RESULTS: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05). CONCLUSION: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA. PMID- 7783055 TI - Characterization and regulation of CD69 expression on rheumatoid arthritis synovial fluid T cells. AB - OBJECTIVE: To study CD69+ synovial fluid (SF) T cells and the mechanisms regulating CD69 expression in rheumatoid arthritis (RA). METHODS: One or 2 color flow cytometry was used to determine CD69 and other surface markers. Cultures of SF T cells alone or mixed with autologous SF non-T cells were used for CD69 maintenance assays. RESULTS: SF T cells were enriched in CD69+. These cells were mainly CD3+, CD8+ and CD25-. CD69 was maintained on SF T cells cultured with SF non-T cells but not when the former were cultured alone or in the presence of different supernatants from RA SF T and non-T cells cultures with sustained CD69 expression. Pretreatment of T and non-T cells with anti-CD18 monoclonal antibody inhibited CD69 expression, while paraformaldehyde-"fixed" non-T cells effectively maintained it. CONCLUSION: SF T cells exhibit a phenotype with evidence of past and recent activation. Our studies demonstrate that most of the recently activated SF T cells are CD8+. We also found that continuous cell-to-cell interaction between T and non-T cells are responsible for the maintenance of this particular state of activation of SF T cells. PMID- 7783056 TI - Isolated microscopic hematuria in patients with rheumatoid arthritis compared with age and sex matched controls. A population based study. AB - OBJECTIVE: To evaluate the prevalence and causes of isolated microscopic hematuria in patients with rheumatoid arthritis (RA). METHODS: An unselected population of 1018 patients with RA (810 women, 208 men) were studied prospectively (n = 604) or retrospectively (n = 414), and the results were compared with an age and sex matched control population (n = 457; 352 women, 105 men). Hematuria was defined as a positive dipstick result in 2 urine samples, and was regarded as isolated when no concomitant proteinuria was found (urine protein excretion < or = 0.15 g/24 h). To investigate the urological causes of isolated hematuria, urine cytology, renal ultrasound, and urethrocystoscopy were undertaken. Renal biopsy was performed when no urological lesions were found. RESULTS: There was no difference in the prevalence of isolated hematuria between patients with RA and controls (women 10 and 9%, men 5 and 6%, respectively; total 9% for both). Mild mesangial glomerulopathy was the most common renal biopsy finding in patients with RA with isolated hematuria, found in 13 of 15 adequate renal biopsy specimens. The cause of hematuria remained uncertain or unknown in 52% of the patients with RA and in 61% of controls. CONCLUSION: The prevalence of isolated microscopic hematuria was not significantly more frequent in patients with RA than in age and sex matched controls. This result was independent of the definition or grade of hematuria. Mesangial glomerulopathy was the most common renal biopsy finding in patients with RA with isolated hematuria. PMID- 7783057 TI - The correlates of health perceptions in rheumatoid arthritis. AB - OBJECTIVE: Although measures of health perceptions have been routinely incorporated into assessments of individuals with rheumatoid arthritis (RA), the relationships of other characteristics of these individuals to their health perceptions is not fully understood. We describe the cross sectional associations of sociodemographic, disease, and functional status characteristics with perceived health in individuals with RA. METHODS: This description was generated through a 2-phase secondary data analysis using 2 statistical approaches: recursive partitioning of the sample and standard multivariate logistic regression techniques. RESULTS: Both methodological approaches identified education, race, depression, and physical activity as important correlates of self-assessed health in RA. Each approach, in its own way, also identified an interactive effect between physical activity and education and between depression and race in these models. CONCLUSION: An individual's sociodemographic, disease, and functional status characteristics form a complex model of the correlates of health perceptions of individuals with RA. PMID- 7783058 TI - Osteoporosis in rheumatoid arthritis: findings in the metacarpal, spine, and hip and a study of the determinants of both localized and generalized osteopenia. AB - OBJECTIVE: To determine the relationship between axial and peripheral bone density in patients with rheumatoid arthritis (RA) compared to controls. To study risk factors for axial and peripheral bone loss in RA. METHODS: Twenty women with RA and 20 age matched controls underwent dual energy x-ray absorptiometry (DXA) of the spine and hip and microradioscopy of the hands in order to quantify the combined cortical thickness (CCT) of the 2nd metacarpal. Sharp's method was used to assess the degree of joint space narrowing and erosions. RESULTS: Compared to controls, the RA group had significantly decreased bone density at the hip (0.761 g/cm2 vs 0.852 g/cm2, p < 0.05) and at the 2nd metacarpal (3.77 vs 4.39 mm, p < 0.05), but not at the spine (0.960 vs 0.947 g/cm2, NS). In patients with RA, measurement of the CCT did not predict bone density at the spine or hip (r = 0.07, NS, and r = 0.095, NS, respectively), whereas in controls, the CCT was significantly correlated with bone density at both these axial sites (r = 0.47, p < 0.05, and r = 0.64, p < 0.01, respectively). Grip strength in RA was correlated with the CCT (r = 0.62, p < 0.01), implying a relationship between hand function and local bone density. Sharp's method did not correlate with axial bone density, but it was strongly correlated with the CCT (r = -0.64, p < 0.01). CONCLUSION: In RA, the CCT is not a useful screen for osteoporosis at the spine or hip. This suggests that localized and generalized osteopenia in RA are best viewed as independent processes. PMID- 7783059 TI - Effects of tenidap on leukocyte-endothelial cell adhesion in mesenteric venules. AB - OBJECTIVE: To compare the proinflammatory effects of tenidap to those of indomethacin, and to assess the influence of lipoxygenase inhibition with either a leukotriene synthesis inhibitor (L663,536) or tenidap on platelet activating factor (PAF) induced leukocyte adhesion. METHODS: Adherent leukocytes, emigrated leukocytes, number of rolling leukocytes/100 microns venule, flux of rolling leukocytes, and leukocyte rolling velocity were quantitated in mesenteric venules (25-35 microns diameter and > 150 microns length) of Sprague-Dawley rats using intravital microscopy. In some experiments, the mesentery was superfused with indomethacin (25 micrograms/ml), tenidap (30 micrograms/ml), or both drugs simultaneously. In other experiments the mesentery was superfused with PAF 100 nM and the effects of treatment with L663,536 (10 mg/kg given orally) or superfusion with tenidap were determined. RESULTS: Indomethacin significantly increased leukocyte rolling and adhesion. Tenidap did not promote leukocyte-endothelial cell adhesion and blocked the increased leukocyte rolling and adhesion promoted by indomethacin. Both L663,536 and tenidap significantly attenuated PAF induced leukocyte-endothelial cell adhesion. CONCLUSION: Tenidap does not exhibit the proinflammatory properties of indomethacin. The reduction of indomethacin or PAF induced leukocyte-endothelial cell adhesion by tenidap appeared to result from its lipoxygenase inhibitory activity. Modulation of leukocyte-endothelial cell adhesion may be a novel mechanism of the antiinflammatory activity of tenidap and may reduce the relative risk of gastric ulceration with tenidap. PMID- 7783060 TI - Dietary treatment of hyperlipidemia in patients with systemic lupus erythematosus. AB - OBJECTIVE: To evaluate dietary therapy in the treatment of hyperlipidemia in patients with systemic lupus erythematosus (SLE). METHODS: Using the National Cholesterol Education Program (NCEP) guidelines, we screened 89 patients with SLE for hyperlipidemia. Step 1 dietary therapy was instituted in 28 patients as recommended by the NCEP. Twenty-six patients failed Step 1 intervention and received Step 2 dietary therapy for an additional 3 months. Twenty-nine control patients with SLE were tested for hyperlipidemia. RESULTS: The 89 patients with SLE (94% women, 77% black) had a mean age of 37.2 years. Fasting values were total cholesterol (TC) 6.22 +/- 0.16 mmol/l (240.9 +/- 6.0 mg/dl), low density lipoprotein cholesterol (LDL-C) 4.08 +/- 0.14 mmol/l, (157.6 +/- 5.3 mg/dl), high density lipoprotein (HDL-C) 1.37 +/- 0.08 mmol/l (53.0 +/- 3.1 mg/dl), and triglyceride (TG) 1.71 +/- 0.12 mmol/l, (151.9 +/- 10.6 mg/dl). The mean dose of prednisone was 14.2 +/- 1.6 mg/day. Prednisone dose correlated with levels of TC (p < 0.01) by linear regression. The 28 patients receiving Step 1 dietary intervention had TC 6.11 +/- 0.19 mmol/l (236.4 +/- 7.3 mg/dl), LDL-C 4.05 +/- 0.19 mmol/l (156.6 +/- 7.5 mg/dl), HDL-C 1.31 +/- 0.08 mmol/l (50.7 +/- 3.0 mg/dl), and TG 1.64 +/- 0.12 mmol/l (145.4 +/- 10.3 mg/dl). The 26 patients receiving Step 2 dietary intervention had TC 5.84 +/- 0.17 mmol/l (226.0 +/- 6.6 mg/dl), LDL-C 3.83 +/- 0.19 mmol/l (148.0 +/- 7.2 mg/dl), HDL-C 1.25 +/- 0.08 mmol/l (48.5 +/- 3.2 mg/dl), and TG 1.66 +/- 0.15 mmol/l (147.1 +/- 13.4 mg/dl). The mean prednisone dose was 14.8 +/- 3.0 mg/day for both study groups. There was no significance between prednisone doses in all groups studied (p = 0.08). After 6 months of dietary therapy, there was a significant decrease in only the TC (p = 0.158). CONCLUSION: TC correlated directly with the prednisone dose. Six months of dietary intervention was required to significantly decrease the TC. Further management of hyperlipidemia will probably require drug intervention. PMID- 7783061 TI - Dyspnea in ambulatory patients with SLE: prevalence, severity, and correlation with incremental exercise testing. AB - OBJECTIVE: We sought to determine the prevalence and severity of dyspnea, and to correlate dyspnea with clinical features and exercise limitation in ambulatory patients with systemic lupus erythematosus (SLE). METHODS: Twenty-five consecutive patients were evaluated with a validated pulmonary questionnaire, chest radiograph, 2-dimensional echocardiography, resting pulmonary function tests, and incremental exercise testing. RESULTS: Dyspnea was reported by 60% (95% CI 39-79) of patients; 20% (95% CI 7-40) had severe dyspnea (inability to dress without dyspnea) and 12% (95% CI 3-31) had moderate dyspnea (dyspnea after walking 100 yards). Compared to patients without dyspnea, patients with dyspnea were more likely to have had a history of clinical lupus involving the lung (80 vs 40%, p = 0.05), a lower total lung capacity (77.5 vs 94.8%, p = 0.002), and a reduced maximum oxygen consumption (VO2max of 53.4 vs 67.7%, p = 0.01). Patients with severe dyspnea and patients without dyspnea did not differ in duration of prednisone use, activity of disease, weight, or in frequency of Raynaud's phenomenon (p > 0.05). Only 4% of all patients had abnormal left ventricular motion on 2-dimensional echo; patients with moderate or severe dyspnea had normal left ventricular motion. Of the 5 patients with severe dyspnea, 4 (80%) had restrictive lung disease and 1 (20%) had an isolated diffusion defect. All patients with dyspnea had an abnormal exercise test, but so did 9/10 without dyspnea (p > 0.05). Severity of dyspnea correlated highly with maximum exercise tolerance measured by VO2max (R2 = 0.51, p = 0.0001). CONCLUSION: In ambulatory patients with SLE, dyspnea is common, frequently disabling, associated with a history of lupus involvement of the lung, and correlates highly with objective measures of exercise limitation. PMID- 7783062 TI - A pilot study of zileuton, a novel selective 5-lipoxygenase inhibitor, in patients with systemic lupus erythematosus. AB - OBJECTIVE: This is a pilot study of zileuton, a selective 5-lipoxygenase inhibitor in systemic lupus erythematosus (SLE). METHODS: Forty patients with SLE received zileuton 600 mg qid or placebo in an 8 week, randomized prospective, double blind trial. Disease activity was manifested largely by constitutional, articular, and skin manifestations with no evidence of active renal, cardiac, or neurologic involvement. Concomitant administration of nonsteroidal antiinflammatories, corticosteroids, or antimalarials was not permitted. Disease activity was determined at baseline and at Days 15 and 57 by assessment of arthritis severity, the Systemic Lupus Activity Measure (SLAM), investigator and patient global ratings, hematologic indices, and serologic measures including autoantibody titers, complement levels, and interleukin 2 receptors (IL-2R). Total body sulfidopeptide leukotriene synthesis was measured by urinary leukotriene E4 (LTE4) concentrations. RESULTS: Overall SLAM (the primary measure of efficacy in this study) was significantly improved with zileuton compared with placebo (-2.1 +/- 1.3, compared with an increase of 2.3 +/- 1.3 with placebo by Day 57, p = 0.048). Changes in individual SLAM subscores, arthritis severity, global ratings, and IL-2R levels compared with baseline did not achieve statistical significance, but were generally decreased from baseline with zileuton (indicating trends towards improvement) and increased from baseline with placebo (indicating trends towards clinical worsening). Urine LTE4 levels at Day 57 had increased from baseline in the placebo group (indicating worsening) and decreased in the zileuton group (indicating improvement). CONCLUSION: Selective 5 lipoxygenase inhibition may be beneficial in mild SLE. PMID- 7783063 TI - Limited scleroderma is associated with increased prevalence of macrovascular disease. AB - Microvascular involvement in scleroderma is well recognized. Macrovascular disease is not. OBJECTIVE. To test the hypothesis that the prevalence of macrovascular disease is increased in patients with limited scleroderma (systemic sclerosis, lSSc). METHODS. A retrospective cohort study design was employed in which the prevalence of macrovascular disease in all female patients from specified hospitals (1974-90) with lSSc of at least 5 years' duration was compared and contrasted with that in a comparable group of controls. Each control was matched to one lSSc case by sex; age (+/- 5 yrs); number of inpatient admissions (+/- 2); year of last hospital admission (+/- 2 yrs), history of hypertension, cigarette smoking and diabetes mellitus, and medical record number most closely approximating the case. The distribution of vascular disease was assessed in the peripheral, coronary, and cerebral arterial territories. RESULTS. Peripheral macrovascular disease (PVD) occurred in 18 (58%) of the lSSC patients and only 3 (9.6%) of the controls (RR = 6.0; 95% CI 2.0-18). Of the 18 lSSc cases, 8 had PVD documented angiographically, 4 by arterial Doppler ultrasound, and 6 had absent peripheral pulses. Five of these required subsequent partial limb amputation. Two of the 3 controls with PVD had absent peripheral pulses, and 1 had an angiographically documented abdominal aortic aneurysm. No control required limb amputation. There was no significant difference in the prevalence of coronary artery or cerebrovascular disease between the groups. CONCLUSION. The prevalence of peripheral large vessel occlusive disease is increased in lSSC and associated with severe morbidity. PMID- 7783064 TI - Muscle strength assessment in polymyositis and dermatomyositis evaluation of the reliability and clinical use of a new, quantitative, easily applicable method. AB - OBJECTIVE: To evaluate the feasibility and the reliability of a quantitative method of maximal isometric strength measurement for the assessment of patients with myositis in clinical practice and research. METHODS: Three observers independently examined the strength of 13 muscle groups of 7 patients with stable polymyositis and dermatomyositis (PM/DM) using a handheld pull-gauge. Reliability was assessed following a balanced random 3-way cross classification with interactions and using the analysis of variance method. Serial followup strength data for 2 patients were compared to change in creatinine kinase (CK) levels. RESULTS: All measurements could be performed without causing pain to the patients. One single test including 13 muscle groups was done in 7 min or less. Both intra and interobserver correlations were strong and significant for all muscle groups. The intraobserver reliability ranged from 0.88 for elbow extensors to 0.98 for knee extensors and cervical spine flexors. The interobserver reliability ranged from 0.81 for elbow flexors to 0.98 for knee extensors and cervical spine flexors. The followup of 2 cases yielded moderate to strong correlations of serial strength measurements with CK levels. CONCLUSION: Serial measurement of isometric muscle strength with a handheld pull-gauge is a feasible, inexpensive, time efficient and reliable method and may provide additional quantitative information in the clinical assessment of patients with myositis. PMID- 7783065 TI - Lack of sensitivity of indium-111 mixed leukocyte scans for active disease in Takayasu's arteritis. AB - OBJECTIVE: Currently, a reliable, noninvasive means of detecting the active vasculitic lesions of Takayasu's arteritis does not exist. Based on the cellular infiltrates seen in active lesions, we postulated that indium-111 labelled mixed leukocytes could be used to scintigraphically detect sites of active vasculitis. METHODS: Fifteen In-111 mixed leukocyte scans were performed in 10 patients with Takayasu's arteritis and correlated with clinical, laboratory, and radiographic findings. Patients had either active, stable/smoldering, or inactive disease at the time when 8, 4, and 3 scans were performed, respectively. RESULTS: Two of the 8 scans performed in patients with active disease were positive for increased vessel uptake (sensitivity = 25%). All other scans were interpreted as negative for active arteritis. CONCLUSION: We conclude that In-111 mixed leukocyte scans have a low sensitivity for detection of active Takayasu's arteritis. PMID- 7783066 TI - Variability in the attainment of functional milestones during the acute care admission after total joint replacement. AB - OBJECTIVE: To quantify patients' functional improvement in the immediate postoperative period after total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: A prospective observational study design was used to examine the number of physical therapy treatment sessions and postoperative days required to attain independence in 4 critical functional milestones, with independence defined as the ability to perform the activity without the assistance of another person. The 4 functional milestones selected were the ability to perform supine to sit transfers; sit to stand transfers; ambulation to 100'; and the ability to climb stairs. Consecutive patients undergoing elective THA or TKA for the first time at a community teaching hospital were entered into the study. RESULTS: The study group consisted of 81 patients undergoing elective THA or TKA (33 THA and 48 TKA). There was wide variability in the number of physical therapy sessions and postoperative days required to attain each of the 4 milestones and all 4 milestones. Climbing stairs was the most difficult task, followed by walking 100', performing sit to stand transfers, and performing supine to sit transfers. The achievement of the latter 2 milestones was similar. CONCLUSION: Our examination of patients' progress in attaining specific functional milestones is a unique approach to outcome assessment that emphasizes the physical therapy aspect of postsurgical rehabilitation. A wide variability in patients' functional progress during the acute care admission after elective THA or TKA was demonstrated. The reasons for this variability need to be explored since they may have important implications for planning rehabilitation related to THA, TKA or other orthopedic reconstructive procedures. PMID- 7783067 TI - The association of body weight, body fatness and body fat distribution with osteoarthritis of the knee: data from the Baltimore Longitudinal Study of Aging. AB - OBJECTIVE: To examine the association of body weight, body fatness, and body fat distribution with osteoarthritis (OA) of the knee. METHODS: Bilateral standing knee radiographs, taken between 1985 and 1991, of 465 Caucasian men and 275 Caucasian women subjects aged 40 and above in the Baltimore Longitudinal Study of Aging were read by one investigator for grade of OA using Kellgren-Lawrence scales. Measures of obesity, assessed at same visit as the last radiograph during this interval, included body mass index, percent body fat, and body fat distribution. RESULTS: Both men and women with definite knee OA had higher age adjusted mean levels of body mass index, while women only had higher age adjusted mean levels of percent body fat. Both women and men in the highest tertile of body mass index had significantly increased odds of both definite and bilateral knee OA; women in the middle and highest tertile of percent body fat had significantly increased odds of both definite and bilateral knee OA, and men in the highest tertile of waist-hip ratio had significantly increased odds of bilateral knee OA. After adjusting for body mass index, however, the association of percent body fat and waist-hip ratio with knee OA in women and men, respectively, was no longer significant. CONCLUSION: These data further extend observations that body weight is associated with both definite and bilateral knee OA in both sexes, and support a stronger contribution of mechanical as opposed to systemic factors to explain this association. PMID- 7783069 TI - Visceral larva migrans mimicking rheumatic diseases. AB - OBJECTIVE: To report rheumatologic or rheumatologic-like manifestations of the visceral larva migrans (VLM) syndrome. METHODS: We carried out a prospective study of patients with VLM seen in a private practice setting in Mexico City between 1990 and 1993. RESULTS: From a population of 600 patients we identified 6 patients (5 women) with VLM. Three patients complained of arthralgia; in 4 a history of migratory cutaneous lesions was elicited, and in one monoarthritis of the right knee was found. One patient had deep edema that suggested thrombophlebitis of the right arm; the man in our series had right testicular swelling during followup. In 2 cases, panniculitis was documented by biopsy and in one, small vessel vasculitis. Four patients had frequent contact with dogs and one with cats; 4 patients frequently ate raw fish. The diagnosis of VLM was confirmed either by the clinical picture, biopsy, or ELISA: CONCLUSION: The spectrum of rheumatological manifestations in VLM may be wider than previously thought. PMID- 7783068 TI - Does renal impairment protect from gout? AB - OBJECTIVE: To test whether renal impairment protects from the development of gout. METHODS: We conducted a retrospective cohort study in which 40 hyperuricemic patients (serum uric acid > 0.54 mM/l) with renal impairment (serum creatinine > 200 microM/l) and 40 equally hyperuricemic patients with normal renal function (serum creatinine < 120 microM/l) were given a telephone questionnaire eliciting a history of gout, its pattern and severity, and other features of medical and family history. RESULTS: There was no significant difference among the prevalence of gout (relative risk 1.1, confidence interval 0.73-1.67), the pattern and severity of gout, and the presence of tophi between the 2 groups. A positive family history of gout was significantly increased in the patients with gouty arthritis (p < 0.05). CONCLUSION: Renal impairment does not protect from gout. There may be a familial factor in the development of gout that is independent from the familial tendency for hyperuricemia. PMID- 7783070 TI - High prevalence of undetected carpal tunnel syndrome in patients with fibromyalgia syndrome. AB - OBJECTIVE: To assess the prevalence of carpal tunnel syndrome (CTS) in patients with fibromyalgia syndrome (FM). METHODS: A series of 206 consecutive patients with FM was evaluated for CTS in an unblinded, uncontrolled study. Sixty patients with dermatomal paresthesia in the fingers enervated by the median nerve were evaluated with electromyogram and nerve conduction velocity studies (EMG/NCV). RESULTS: Thirty-three patients showed EMG/NCV findings diagnostic for CTS (16% of the 206 cases, 55% of the 60 EMG studies). Only 2 of the 33 patients with CTS had been diagnosed before rheumatologic evaluation. We compared our results with those reported for women in the general population. The overall prevalence of CTS in women was higher (16 vs 10.2%), but not statistically different. However, in our series, there was a clear difference in the higher rate of undetected CTS in women with FM compared to that of the general population (14.1 vs 6.7%) (p < 0.01). CONCLUSION: (1) CTS is at least as common in patients with FM as in the general population, contrary to that reported in retrospective studies; (2) the rate of underdiagnosed CTS in women with FM is much higher than the rate reported in the general population; (3) NCV studies may be necessary to evaluate underdiagnosed CTS in patients with FM and dermatomal paresthesia in their hands. PMID- 7783071 TI - Musculoskeletal disability, employment, and rehabilitation. AB - OBJECTIVE: To determine which, if any, baseline social and disease characteristics can be used to identify persons with musculoskeletal disabilities accepted for state-federal vocational rehabilitation services who are most likely to return to work. METHODS: A database of case closures from the Alabama Vocational Rehabilitation Service was analyzed using segmentation modelling. This included all persons (n = 4093) with musculoskeletal disability who were accepted by the Alabama Vocational Rehabilitation Agency in 1987-91. Demographics, income, type of disability, severity of disability, medical insurance, similar benefits, benefit status, and referral source were independent variables. Outcome (dependent) variable was work status at end of agency services. RESULTS: Overall, 71% of persons with arthritis and musculoskeletal disorders who were accepted for vocational rehabilitation services in 1987-91 returned to work at the end of agency services. Segmentation modelling created a tree in which certain baseline characteristics formed subgroups with differing rates of successful rehabilitation. Social Security Disability Insurance (SSDI) status was the single best predictor of rehabilitation. Seventy-three percent of nonbeneficiaries were rehabilitated compared to 55% of beneficiaries (p < 0.00001). For non-SSDI beneficiaries, education level > or = grade 12 was associated with better rehabilitation outcome (p < 0.00001). SSDI beneficiaries with nonback disorders fared better than those with back disorders (p < 0.05). Disease severity, assessed by Federal Special Programs criteria, was not associated with rehabilitation outcome at any level of the tree. CONCLUSION: Simple baseline social and disease characteristics can be used to identify groups of persons accepted for vocational rehabilitation services with musculoskeletal disability with differing rates of vocational rehabilitation. Disability benefit status and education level are important predictors of return to work after agency services. These findings can lead to the development of strategies to improve the efficacy of vocational rehabilitation services. PMID- 7783072 TI - The relationship between self-reported pain and sociodemographic variables, anxiety, and depressive symptoms in rheumatoid arthritis. AB - OBJECTIVE: Self-reported pain is one of the core endpoint measures in RA. The objective of this cross sectional study of 238 patients with rheumatoid arthritis (RA) was to examine the relationship between self-reported pain intensity, sociodemographic variables, anxiety, and depressive symptoms. METHODS: A weighted sum score of pain intensity was constructed by combining a visual analog pain scale with items from the Arthritis Impact Measurement Scales (AIMS) and the Nottingham Health Profile. Symptoms of anxiety and depression were measured by subscales of AIMS: RESULTS: Multiple regression analyses showed no significant effects of age, sex, income, or level of education on self-reported pain intensity, whereas there was a significant association between the pain index and anxiety and depressive symptoms. The correlation between the pain index and anxiety, and the pain index and depression, was 0.46 for both. Controlling for sociodemographic variables, the Ritchie index, erythrocyte sedimentation rate, and C-reactive protein, the standardized regression coefficients were 0.33 and 0.31 of the pain index on the AIMS anxiety and depression subscale, respectively. Furthermore, the results indicate that the effect of inflammation on mental distress is mediated by pain. CONCLUSION: Self-reported pain in RA is not significantly influenced by sex, age, level of education, or income. Even when controlling for disease activity, there was a considerable correlation between self-reported pain and mental distress. Furthermore, our study lends support to the hypothesis that mental distress is mainly secondary to pain rather than vice versa. PMID- 7783073 TI - Autoantibodies to the nucleolar organizer antigen NOR-90 in children with systemic rheumatic diseases. AB - OBJECTIVE: To determine the frequency of autoantibodies directed against the nucleolar organizer antigen NOR-90 [human upstream binding factor (hUBF)] in pediatric patients with systemic rheumatic diseases. Two children with antibodies to NOR-90 are reported. METHODS: Two hundred thirty-eight sera from children with systemic rheumatic diseases were screened for autoantibodies directed against hUBF by indirect immunofluorescence and immunoblotting using MOLT-4 cell extracts. Reactivity with hUBF was confirmed by immunoprecipitation of the recombinant hUBF protein. RESULTS: Two sera out of 238 (< 1.0%) with reactivity against hUBF were identified. One patient had recurrent abdominal pain, headache, and Raynaud's phenomenon. There has been no evidence of an active systemic rheumatic disease in more than 8 years of followup. The 2nd patient had Raynaud's phenomenon and systemic lupus erythematosus. CONCLUSION: Antibodies to hUBF are rare in children with systemic rheumatic diseases. Raynaud's phenomenon was a clinical feature common to both patients. PMID- 7783074 TI - Fibromyalgia syndrome in children--an outcome study. AB - OBJECTIVE: To assess the outcome of fibromyalgia syndrome (FM) in a 30-month followup study of children with FM. METHODS: In the original study to assess the prevalence of FM in healthy schoolchildren, we found 21 children with FM and an additional 7 fulfilling the point count criterion only (11 of 18). Fifteen of the 21 and all 7 were recruited for a 2nd assessment in our present study. In all children, a count of 18 tender points (TP) was conducted by thumb palpation. Tenderness of 9 of the TP sites as well as 4 control point sites was further assessed using a Chatillon dolorimeter. All children were questioned concerning the presence of widespread pain or aching. Children were considered to have FM if they met the American College of Rheumatology criteria for diagnosis. RESULTS: After 30 months, 11 of the 15 children with FM (73%) were no longer fibromyalgic. The mean point count of the 15 children significantly decreased from 12.5 to 4.6 (p < 0.001). The mean tenderness threshold of the 9 tender sites increased from 2.4 to 3.4 kg (p < 0.01), and the mean tenderness threshold of the 4 control sites increased from 4.1 to 5.6 kg (p < 0.05). Of the 7 children initially fulfilling the point count criterion only, none had developed FM. Their mean point count decreased from 11.4 to 3.4 (p = 0.001), and their mean tenderness thresholds increased from 2.7 kg to 3.9 kg (p = 0.001) at tender sites and from 4.3 kg to 6.8 kg (p < 0.001) at control sites. CONCLUSION: We suggest that the outcome of FM in children is more favorable than in adults. More followup studies are needed to clarify the longterm outcomes of FM in children and adults. PMID- 7783075 TI - Poststreptococcal reactive arthritis in children: a potential predecessor of rheumatic heart disease. AB - OBJECTIVE: To report several cases of arthritis seen in children after infection with Group A beta-hemolytic Streptococcus (GABHS) which were not associated with carditis or other major manifestations of the Jones Criteria for acute rheumatic fever (ARF); and to analyze the literature to determine these patients' potential risks for the subsequent development of rheumatic heart disease. METHODS: A retrospective chart review was performed of all patients seen in a pediatric rheumatology clinic from January, 1990 to December, 1992. RESULTS: Four patients were identified with poststreptococcal reactive arthritis (PSReA) and no carditis. Their arthritis had an acute onset, tended to have a longer duration than the arthritis typically seen in ARF, and in most instances did not respond promptly to therapy with aspirin or nonsteroidal antiinflammatory agents. In some patients, there was no history of sore throat or fever. Diagnosis of PSReA was made by serologic testing. Cardiac evaluation in all 4 patients was negative. CONCLUSION: PSReA should be considered in the differential diagnosis for any pediatric patient with the acute onset of arthritis, whether the arthritis is the classic migratory polyarthritis typically seen in ARF or not. Throat culture and serologic testing for streptococcal infection should be performed on these patients. If recent GABHS infection is confirmed, cardiac evaluation, including echocardiogram, is warranted. Both ARF and PSReA occur after GABHS infection, but the precise relationship between these 2 entities is unclear. Longterm follow up of pediatric patients with PSReA in previous reports have shown that a certain percentage of them upon subsequent GABHS infection develop carditis. Until the specific risk factors (either host or bacterial characteristics) for developing subsequent carditis are better delineated, antibiotic prophylaxis similar to that used in ARF should be considered in patients with PSReA. PMID- 7783077 TI - Isolated congenital complete heart block: longterm outcome of children and immunogenetic study. AB - OBJECTIVE: To assess the longterm cardiologic and immunologic outcome of children with isolated congenital complete heart block (CCHB) and their HLA antigens. METHODS: Sixteen children with isolated CCHB were investigated. HLA typing was done using a microcytotoxicity test. RESULTS: Three patients died (18.7%), one in utero (35 weeks), one 2 days after birth, and one at 6 years of age. The mean age of the 13 living children is now 18.3 years (range 2-34). Eight (50%) have been permanently paced for symptoms. No patient developed clinical symptoms or serological abnormalities suggesting immune disease. The A31 antigen was more prevalent, but one pair of HLA identical twins was observed, and only one had CCHB. CONCLUSION: Patients with isolated CCHB have significant cardiac mortality, and after a long followup many of them are paced to control symptoms, but in our small sample those who survive the perinatal period mostly lead a normal life. The longterm immunological outcome of these children seems good. CCHB is not related to a specific HLA pattern in affected children. PMID- 7783076 TI - Isolated congenital complete heart block: longterm outcome of mothers, maternal antibody specificity and immunogenetic background. AB - OBJECTIVE: To assess the longterm outcome of mothers of children with isolated congenital complete heart block (CCHB), and the maternal specific immunoblot pattern and HLA antigens. METHODS: Fifteen mothers of 16 children with isolated CCHB were investigated; their followup extended up to 15.8 years on average after the index delivery. Anti-Ro and La antibodies were detected by counterimmunoelectrophoresis and ELISA; anti-Ro antibodies were studied by immunoblot. HLA typing was done using a microcytotoxicity test. RESULTS: One mother has systemic lupus erythematosus (SLE) before the index delivery. The other mothers developed only minor symptoms (arthralgia, dry eyes and photosensitivity) resembling primary Sjogren's syndrome more than classic lupus. All 15 mothers were anti-Ro and 9 were also anti-La positive, a mean of 12.5 years after the index delivery. Eight mothers reacted with the 52 kDa SSA(Ro) component, and 2 also with the 60 kDa SSA(Ro) component. The prevalence of the DR3 antigen and of the B44/DR5, DR3/DQ2 and A1/Cw7/B8/DR3/DQ2 haplotypes was significantly increased. CONCLUSION: The longterm outcome for the mothers of children with CCHB is more reassuring than generally assumed. All the mothers were anti-Ro positive by sensitive ELISA: Reactivity to the denaturated 52 kDa SSA(Ro) component seems characteristic of these mothers, who presented a particular immunogenetic background. PMID- 7783078 TI - Anorexia nervosa presenting as a peripheral vasculopathy in an adolescent male. PMID- 7783080 TI - Subsynovial vascular abnormality causing recurrent hemarthrosis in an 84-year-old man. AB - We describe a patient with recurrent hemarthrosis of one knee. Investigation demonstrated a vascular abnormality of the synovium as the likely cause. Structural abnormalities of the synovial vasculature should be considered, in the absence of a systemic cause, as a potential source of bleeding in older patients with recurrent hemarthrosis. PMID- 7783079 TI - Atlantoaxial subluxation in children with seronegative enthesopathy and arthropathy syndrome: 2 case reports and a review of the literature. AB - We describe 2 HLA-B27 positive children with seronegative enthesopathy and arthropathy (SEA) syndrome who developed spontaneous (nontraumatic) atlantoaxial subluxation early in their disease course. Neither child had evidence of spinal cord compression but both had progressive atlantoaxial subluxation in spite of conservative treatment. Both underwent elective posterior cervical (C1-C2) fusion. PMID- 7783081 TI - Pulmonary capillaritis and alveolar hemorrhage associated with the antiphospholipid antibody syndrome. AB - Pulmonary hemorrhage due to small vessel vasculitis is a well recognized complication of many autoimmune and collagen vascular disorders. The antiphospholipid antibody syndrome (APS) is a disorder associated with hypercoagulability, thrombocytopenia, and thromboembolic phenomena. Pulmonary manifestations include pulmonary embolism, pulmonary hypertension, and respiratory failure associated with diffuse pulmonary infiltrates. We describe a patient with the APS syndrome, without systemic lupus erythematosus, who developed pulmonary hemorrhage due to pulmonary capillaritis with evidence of perivascular immune complex deposition. PMID- 7783082 TI - Systemic sclerosis sine scleroderma: an unusual presentation in scleroderma renal crisis. AB - Renal involvement in systemic sclerosis (SSc) has a negative influence on prognosis. Cases of SSc sine scleroderma have been reported in which organ failure occurred but was not accompanied by cutaneous damage, which in some instances did develop later. We describe a patient who, after 6 months of symmetric polyarthritis, developed rapid progressive renal failure without skin changes. A diagnosis of scleroderma renal crisis, confirmed histologically, was made. Anti-RNAP III antibodies were positive. The patient developed typical scleroderma skin changes after renal failure. Despite treatment, SSc advanced to fatal endstage renal disease. PMID- 7783083 TI - Milwaukee shoulder associated with primary hyperparathyroidism. AB - We describe a 69-year-old woman with a Milwaukee shoulder syndrome in the presence of primary hyperparathyroidism. After removal of a parathyroid adenoma, effusion of the shoulder did not recur. We believe that primary hyperparathyroidism and Milwaukee shoulder can be causally related. PMID- 7783084 TI - Serum aldolase level is a useful indicator of disease activity in eosinophilic fasciitis. AB - The serum levels of muscle enzymes have been considered normal in patients with eosinophilic fasciitis (EF). We observed elevated serum aldolase levels in 3 patients with EF. Serum creatinine kinase levels were within the normal range. We measured the aldolase levels longitudinally. In all patients, the levels decreased to the normal range after oral corticosteroid treatment, and skin sclerosis improved. Afterwards, serum aldolase levels increased again, with the recurrence of skin sclerosis. These observations suggest that serum aldolase level may be a useful indicator of disease activity. PMID- 7783085 TI - Giant cell arteritis limited to the prostate. AB - We describe a 66-year-old man with giant cell arteritis (GCA) limited to the prostate. His symptoms, which resembled prostatic neoplasia, resolved with systemic steroid therapy. Pathology studies revealed no clinical or histologic data indicating temporal artery involvement. To our knowledge this is the first described case of GCA involving the prostate. PMID- 7783086 TI - Treatment of amyloidosis secondary to rheumatoid arthritis. PMID- 7783087 TI - Prognostic value of rheumatoid factors in rheumatoid arthritis. PMID- 7783088 TI - Automated diagnosis and characterization of Lyme disease using neural network analysis. PMID- 7783089 TI - Gold induced colitis. PMID- 7783090 TI - Hemorrhagic rupture of the shoulder. PMID- 7783091 TI - Polyglandular autoimmune endocrinopathy following procainamide induced lupus. PMID- 7783092 TI - Nontyphoidal salmonella ovarian abscess in systemic lupus erythematosus. PMID- 7783094 TI - Moraxella septic arthritis in an adult. PMID- 7783093 TI - Inclusion body myositis responding to longterm chlorambucil treatment. PMID- 7783095 TI - Poisoning with anti-hypertensive drugs: calcium antagonists. AB - Calcium antagonists are used increasingly to treat hypertension and other conditions, so the possibility of accidental or deliberate self-poisoning is substantially increased. These drugs account for a high proportion of deaths in cases of poisoning associated with cardiovascular drugs. Most of our present knowledge is with the older calcium antagonists, namely verapamil, nifedipine and diltiazem; newer sustained-release preparations of these drugs may produce serious toxicity in patients who initially appear well. This review discusses the cases reported in the literature, the presenting symptoms and the management of patients with calcium antagonist poisoning. PMID- 7783096 TI - Favourable interaction of calcium antagonist plus ACE inhibitor on cardiac haemodynamics in treating hypertension: rest and effort evaluation. AB - The aim of the study was to evaluate the effects of verapamil sustained release (SR) 240 mg, enalapril and their combination on blood pressure (BP) and cardiac haemodynamics at rest and during exercise in 20 patients with moderate essential hypertension (seven men and 13 women, mean age +/- s.d. 53.7 +/- 15.8 years). After a 4 week placebo run-in period, patients were randomly allocated to received verapamil SR 240 mg once daily or enalapril 20 mg once daily for 4 weeks in a double-blind fashion. Patients whose diastolic blood pressure (DBP) was still > or = 95 mm Hg at the end of this period received verapamil SR plus enalapril for an additional 4 weeks. At the end of the placebo, single and combined treatment periods, resting and exercise (bicycle ergometry) haemodynamics were evaluated by radionuclide ventricular angiography (technetium 99m) and the following parameters were assessed: BP, heart rate, double product, systemic vascular resistances (SVR), cardiac output (CO), stroke volume (SV), ejection fraction (EF) mean ejection rate (mER) and peak filling rate (PFR). Both verapamil SR and enalapril monotherapies significantly reduced resting and exercise BP (P < 0.01), with a BP normalisation (DBP < or = 95 mm Hg) of five of 10 and 4 of 10 patients respectively. A greater BP fall and a normalisation of 11 of 11 patients was obtained in non-responders to monotherapy, when treated with verapamil SR and enalapril (P < 0.01). Verapamil SR also reduced heart rate at rest and during exercise (-11.8% and -18.4%, respectively, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783098 TI - Isolated systolic hypertension as a major risk factor for stroke and myocardial infarction and an unexploited source of cardiovascular prevention: a prospective population-based study. AB - The purpose of this study was to determine the prevalence of isolated systolic hypertension (ISH) and associated risk of major cardiovascular events. The Copenhagen City Heart Study is a prospective population survey with cardiovascular examinations at 5-year intervals. Blood pressure measurement was carried out as office blood pressure. ISH was defined as SBP > or = 160 mmHg and DBP < 90 mm Hg. The risk of stroke and myocardial infarction (MI) in association with ISH was assessed using a multivariate Cox regression model. Follow-up was carried out by means of the National Patients Register and Death Register. The 19,698 subjects were randomly selected after age stratification from an area of central Copenhagen. Subjects (n = 6621) were included if > or = 50 years, not on anti-hypertensive or cardiac medicine, and had no history of a previous stroke or MI. Initial cases of verified stroke or MI were recorded from 1976 to 1988. The prevalence of ISH showed an age-related increase from 3% in the 55-year olds to 13% in the 72-year olds. No sex difference was found. Relative risk of stroke corrected for other risk factors was 3.0 (95% CI 1.6-5.3) for women and 2.7 (1.8 4.3) for men. This was the highest relative risk among all hypertensive groups. Relative risk of MI corrected for other risk factors was 0.8 (0.3-2.0) for women and 1.6 (1.0-2.5) for men. Population attributable risk for stroke associated with ISH is up to 30%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783097 TI - Accuracy of an oscillometric automatic blood pressure device: the Omron HEM403C. AB - The purpose of this study was to assess the accuracy of the Omron HEM403C blood pressure (BP) device and to study whether this accuracy was affected by subject related factors such as BP level and age. A comparison was made with a Hawksley random zero sphygmomanometer. BP was measured with both meters connected to one arm-cuff by means of a T-connector. To assess the level of agreement of the Omron HEM403C with the random zero meter, BP was measured in 212 subjects. Systolic and diastolic readings with the Omron HEM403C were on average 1 mmHg (s.d. 9, 95% CI 0.4-2.2) and 4 mm Hg (s.d. 8, 95% CI 3.6-5.1) respectively, higher than those with the random zero meter. The Omron HEM403C underestimated SBP compared with the random zero at higher SBP levels and overestimated SBP at lower SBP levels. The Omron meter overestimated the diastolic pressure at all DBP levels and the diastolic difference was not related to the DBP level. A multiple linear regression analysis demonstrated that the SBP level and not age was the factor that independently influenced the systolic difference between the meters. According to the criteria of the British Hypertension Society the Omron HEM403C is accurate enough to be recommended for those clinical and research purposes that are in need of automatic measurements. PMID- 7783099 TI - Assessment of effects of two anti-hypertensive regimens on overall cardiovascular risk. AB - Anti-hypertensive drugs differ in their effects on other cardiovascular risk factors. To date there have been few attempts to quantitate the impact of such differences. Twenty five unmedicated patients with primary hypertension were randomised to initial therapy with either the calcium antagonist, felodipine, or a diuretic and doses titrated to achieve similar levels of blood pressure (BP). Second drugs were added if needed (metoprolol and prazosin, respectively). The aim was to determine over 1 year whether similar anti-hypertensive effects were associated with differences in a multivariate index of overall cardiovascular risk. The target supine diastolic blood pressure (DBP) (85 mm Hg) required the second agent in four of 13 evaluable patients in the felodipine group and six of 10 in the diuretic group. There was a significant rise in serum cholesterol and a fall in serum potassium in the diuretic group, but not in the felodipine group. Cardiovascular risk scores were ranked in percentiles in relation to the age matched general population. This score fell to a greater degree in felodipine patients particularly over the first 6 months, but remaining lower at 12 months. Left ventricular hypertrophy assessed by echocardiography, another measure of cardiovascular risk, was generally unchanged by either regimen. At equivalent blood pressure levels, the calcium antagonist-based regimen had a greater benefit on cardiovascular risk, particularly in the first 6 months of therapy. This method may be widely applicable in the assessment of anti-hypertensive therapy. PMID- 7783100 TI - Intrarenal production of dopamine and natriuresis following DOPA and saline infusions in healthy human volunteers. AB - The interactions of intrarenal dopamine (DA) synthesis and natriuresis were studied in 11 healthy volunteers by giving a low and high sodium diet (LoSo, 50 mmol Na+; HiSo, 250 mmol Na+). On 2 days in both dietary phases an acute saline load was given, without or with an infusion of the DA precursor 3, 4 dihydroxyphenylalanine (DOPA) 0.15 microgram kg-1 min-1. Urinary excretion rates of sodium (UNa V), DOPA (UDOPA V), DA (UDA V) and noradrenaline (NA; UNA V), hormonal parameters, blood pressure (BP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured. On HiSo UDOPA V increased by 35% (P < 0.05) while UDA V remained unchanged. Only weak correlations were found between 24h UNa V and UDA V (r = 0.23) or UDOPA V (r = 0.39). On both diets and without the DOPA infusions, the saline infusions enhanced UNa V but did not increase UDA V. The DOPA infusions caused no significant change of UNa V, in spite of five- to eight-fold increases in UDA V. During LoSo the DOPA infusion only caused a slightly larger increase of UNa V after the saline infusion, when expressed as percentage change to the pre-saline UNa V (119 +/- 25% without DOPA infusion, 244 +/- 56%, P < 0.05 with DOPA infusion). On HiSo the DOPA infusion did not affect UNA V. The dietary sodium intake and the DOPA infusions did not influenced BP, GFR, or ERPF. In conclusion, dietary sodium intake or acute sodium loads did not clearly modulate UDA V.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783101 TI - Investigation of ambulatory blood pressure monitoring data editing criteria. AB - Ambulatory blood pressure monitoring (ABPM) allows multiple measurements of BP over a 24h period but often produces a proportion of measurements which are distant from the mean and unlikely to be genuine. The software which accompanies the SpaceLabs 90207 monitor requires criteria to be set which excludes outliers (autoediting) but there is no published data evaluating at what levels these autoediting criteria should be set. This study set out to ascertain whether outlying BP measurements represent true blood pressures or machine error, the determinants of machine error and appropriate autoedit criteria. Twenty subjects, both normotensive and hypertensive, were studied by ABPM with a blinded observer recording BP using a standard mercury sphygmomanometer (SMS) connected via a T tube during three activity phases: sitting with cuffed arm still, walking but keeping arm still during measurement and sitting but gently moving the arm during measurement. The results show that a high ABPM/SMS discrepancy is associated with arm movement. After studying different autoediting criteria which aimed to eliminate the maximum number of conflicting readings while excluding the minimum number of unconflicting readings, an autoediting threshold of between 1.75 and 2 s.d.s from the mean based separately on sleep and awake measurements is suggested. PMID- 7783102 TI - Low fasting and insulin-mediated intracellular magnesium accumulation in hypertensive patients with left ventricular hypertrophy: role of insulin resistance. AB - Twenty-five hypertensive patients (13 males/12 females) with left ventricular hypertrophy (LVH) and 12 hypertensive patients (6 males/6 females) without LVH were studied. Both groups were matched for age, sex, body mass index, percentage body fat, arterial BP and known duration of hypertension. After a seven day wash out period from antihypertensive treatment each subject underwent: (1) an oral glucose tolerance test, (2) an euglycemic hyperinsulinaemic glucose clamp (insulin infusion rate 7.1 pM/kg per min), (3) an echocardiographic determination of left ventricular mass index, and (4) 24h ECG Holter monitoring. All tests were performed in random order and on different days. All investigators were unaware of the patient groups. Hypertensive patients with LVH had lower fasting intracellular (erythrocyte) magnesium concentrations (1.85 +/- 0.06 vs. 2.07 +/- 0.04 mM; P < 0.001) but higher fasting plasma insulin concentrations (86 +/- 4 vs. 59 +/- 5 pM; P < 0.001) Glucose clamp study demonstrated a lower insulin mediated glucose disposal (24.8 +/- 0.4 vs. 30.1 +/- 0.3 microM/kg of lean body mass per min; P < 0.05) and a net change in intracellular magnesium accumulation (17.9 +/- 1.3 vs. 27.3 +/- 1.8%, P < 0.01) in response to insulin infusion in hypertensive patients with LVH than in those without LVH. After adjustment for fasting plasma insulin levels and insulin-mediated glucose uptake, fasting and insulin-mediated erythrocyte magnesium accumulation were no longer different between the two groups. In conclusion, hypertensive patients with LVH compared with those without LVH have a lower intracellular magnesium content due a higher degree of insulin resistance. PMID- 7783103 TI - Evaluation of the accuracy and reproducibility of the Takeda TM-2420 in the elderly. PMID- 7783104 TI - Hypertension and left ventricular hypertrophy in black people. PMID- 7783105 TI - Gastrointestinal bleeding induced by amlodipine. PMID- 7783106 TI - Mean platelet volume in human essential hypertension. PMID- 7783107 TI - Calcium channel blockade: is lowering office blood pressure enough? Introduction. PMID- 7783108 TI - Renal effects of amlodipine. AB - The effects of a new dihydropyridine calcium channel blocker, amlodipine, on blood pressure (BP) and renal function were studied in spontaneously hypertensive rats (SHR). These effects were compared with those of an angiotensin-converting enzyme (ACE) inhibitor, enalapril. In addition, the effects of amlodipine on BP and renal function were studied in hypertensive patients with renal impairment. In five of six nephrectomised salt-loaded SHR, increases in BP, urinary excretion of protein and serum creatinine were attenuated by the administration of 2 mg/kg/day of amlodipine. The progression of renal histological damage was also markedly decreased. The protective effects of amlodipine against renal damage were similar to those of enalapril. However, the mechanisms of action of these two agents seem to differ as, unlike enalapril, amlodipine did not significantly dilate the efferent arteriole in hydronephrotic perfused rat kidney. In a clinical study, 2.5-5 mg/day of amlodipine was administered once a day for 8-10 weeks to 39 hypertensive patients with renal impairment (serum creatinine > or = 1.5 mg/dl to < 5 mg/dl) or renal parenchymal disease (serum creatinine < 5 mg/dl). A significant reduction in BP (reduction of mean BP > or = 13 mm Hg) was observed in 28 patients (80%). Headache was experienced as a side-effect in one of 35 patients (2.9%). With respect to the influence of amlodipine on renal function, mean values of blood urea nitrogen and serum creatinine were unchanged for the total group whereas a slight elevation of serum creatinine was observed in four of 35 patients (11.4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783110 TI - Comparative effects of amlodipine and felodipine ER on office and ambulatory blood pressure in patients with mild to moderate hypertension. Danish Multicentre Group. AB - The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5, 10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients with mild to moderate essential hypertension in a double-blind, double-dummy, randomised, comparative study. One hundred and eighteen patients were randomised to receive either felodipine ER (n = 57) or amlodipine (n = 61) for 12 weeks. Efficacy was assessed by measuring office blood pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24h ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment and at the end of the study. The mean office BP changes from baseline to week 12 were -13.4/-11.8 mmHg for felodipine ER (mean daily dose 11.2 mg) and -15.3/-12.9 mm Hg for amlodipine (mean daily dose 7.4 mg). Changes in office BP between treatment groups were not significant. The mean 24h ambulatory BP changes from baseline to end of the study were -11.6/-10.0 mm Hg for felodipine ER and -16.3/-9.6 mm Hg for amlodipine, both significant (P < 0.01). The fall in systolic ambulatory BP was significantly greater (P < 0.001) in the amlodipine-compared with felodipine ER-treated patients but there was no difference between the groups with respect to diastolic ambulatory BP. Both drugs were well tolerated with only seven patients withdrawing because of side-effects, equally distributed between treatment groups. Headache and flushing were significantly (P < 0.05) more frequent in the felodipine ER group. Amlodipine appears to be more potent on a milligram to milligram basis and induces fewer side-effects than does felodipine ER. PMID- 7783109 TI - Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension. AB - In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema for calcium antagonists and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients (eight amlodipine (4%), nine enalapril (4%)) were withdrawn from the trial because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated. PMID- 7783112 TI - Limits of lipid-lowering therapy: the benefits of amlodipine as an anti atherosclerotic agent. AB - Treatment of atherosclerosis has mainly focused on decreasing low-density lipoprotein cholesterol (LDL-C). However, recent coronary angiographic trials revealed that aggressive lowering of LDL-C below 100 mg/dl arrests atherosclerosis progression in only 50-60% of patients. Furthermore, quantitative coronary angiography in these trials showed significant regression only in advanced fibrous-fatty plaques (> or = 50% stenosis) and not in the younger, more cell-proliferative lesions (< 50% stenosis). It is clear that lipid-lowering therapy has limited efficacy and there is therefore a need for other drugs, especially anti-proliferative agents, for secondary and primary prevention. To test this hypothesis, a new calcium antagonist, amlodipine, was studied for its anti-atherogenicity in non-human primates because of its known in vitro anti-cell proliferant, cell membrane stabilising and anti-oxidant properties. Amlodipine was found to normalise elevated plasma levels of oxidised LDL without reducing elevated total LDL-C levels in monkeys fed an atherogenic diet which, however, significantly suppressed atherosclerosis progression. These data suggest that amlodipine may be an excellent candidate, in combination with lipid-lowering drugs, for dual therapy of atherosclerotic vascular disease and may also be effective as monotherapy even when LDL-C is not lowered satisfactorily. PMID- 7783111 TI - Vascular reactivity: a measurement of calcium channel blockade. AB - Clinical studies have shown that calcium antagonist drugs interfere with the reactivity of vascular smooth muscle and thereby attenuate the pressor responses to adrenergic and non-adrenergic vasoconstrictor agents. It is, therefore, possible to explore the extent and duration of calcium channel blockade by studying the magnitude and time course of the attenuation of pressor responses. The effects of three long-acting calcium antagonists, amlodipine, lacidipine and nifedipine GITS (gastrointestinal therapeutic system), on vascular reactivity were assessed over 24h and 48h dosage intervals. It was shown that all three agents attenuate the vasoconstrictor responses to both adrenergic and non adrenergic stimuli. However, amlodipine and nifedipine GITS were found to suppress vascular reactivity more consistently than lacidipine over 24h. Extending the analysis to 48h after dosing showed that amlodipine had the most consistent effect. PMID- 7783113 TI - Calcium channel blockade: is lowering office blood pressure enough? PMID- 7783114 TI - Design and syntheses of potent and selective dipeptide inhibitors of Candida albicans myristoyl-CoA:protein N-myristoyltransferase. PMID- 7783115 TI - A-ring ortho-disubstituted aporphine derivatives as potential agonists or antagonists at serotonergic 5-HT1A receptors. AB - (R)- And (S)-11-hydroxy-10-methylaporphine 1 and 2 are, respectively, a potent, highly specific serotonergic (5-HT1A) agonist and antagonist. In an ongoing structure-activity study, racemates of the positional isomers 8-hydroxy-9-methyl- and 8-methyl-9-hydroxyaporphine were prepared by modifications of literature methods and were resolved. The methyl ethers of the target compounds were also evaluated pharmacologically. All of the free phenolic derivatives [(+)- and (-)-8 and 10] were inert in an assay for 5-HT1A receptor activity. All of the methyl ethers [(+)- and (-)-9 and 11] demonstrated quantitatively similar low potency stimulant effect at 5-HT1A receptors. The agonist or antagonist activity exhibited by 1 and 2 reflects the high degree of structural specificity required of aporphine derivatives for action at 5-HT1A receptors. PMID- 7783116 TI - The cholesterol derivative of a triantennary galactoside with high affinity for hepatic asialoglycoprotein receptor: a potent cholesterol lowering agent. AB - Cholesterol-derivatized galactosides have been devised in order to induce liver uptake of lipoproteins via the galactose-recognizing asialoglycoprotein receptor in the liver. In this study we describe the derivatization of a newly developed triantennary cluster galactoside having high affinity for the asialoglycoprotein receptor, N-[[tris-O-(3,6,9-trioxaundecanyl-beta-D-galactopyranosyl)metho xym ethyl] -N alpha-[1-(6-methyladipyl)]glycinamide (TG(20A)) with cholesterol. Hereto, TG(20A) was coupled to glycine-(5-cholesten-3 beta-yl ester) in the presence of (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, affording N-[[tris-O-(3,6,9-trioxaundecanyl-beta-D- galactopyranosyl)methoxymethyl]methyl]-N alpha-[1-(6-(5-cholesten-3 beta yloxy)glycyl)adipyl]glycinamide (TG(20A)C) in 46% yield. This compound is an amphiphilic, water-soluble compound. In aqueous solution it readily formed small micelles (4.9 +/- 1.2 nm) consisting of approximately 20 molecules. Upon incubation with human serum, TG(20A)C spontaneously incorporated into the most prominent serum lipoproteins, i.e., low-density lipoprotein (LDL) and high density lipoprotein (HDL), thereby inducing an increase in buoyant density of these lipoproteins. The integrity of HDL and LDL, as judged from particle size analysis of both lipoproteins, was not altered by incubation with up to 0.33% of TG(20A)C (w/v). Following intravenous bolus injection into rats, TG(20A)C induced a dose-dependent decrease in the serum cholesterol content of maximally 44%, at a dose of 1.9 mg kg-1. This makes TG(20A)C at least 30-fold more effective than the previously developed N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N alpha [4-(5- cholesten-3 beta-yloxy)succinyl]glycinamide (TG(4A)C), provided with a cluster galactoside that displayed a 2000-fold lower affinity for the asialoglycoprotein receptor than TG(20A). In conclusion, the hypocholesterolemic activity of a cholesterylated galactoside can be strongly enhanced by using a cluster galactoside with higher affinity for the asialoglycoprotein receptor. PMID- 7783117 TI - Preparation and in vitro activities of ethers of [D-serine]8-cyclosporin. AB - Reactions of the [D-serine]8-cyclosporin (2) with a series of alkylating agents under phase transfer conditions gave the alkylated products 3-6. Alkylations of 2 with hindered esters of bromoacetate gave the crystalline esters 7 and 8. Hydrolysis under basic conditions gave the acid 10. Reduction of ester 8 led to a novel cyclosporin 11. This was transformed in two additional steps to 15. In a similar two-step sequence 17 was prepared from 15. From 2 and methyl 2 (bromomethyl)acrylate product 20 was obtained. Alkylation of 2 with 49 followed by deprotection yielded 24. The linear isomer 27 was prepared. The 3 hydroxypropyl ether 30 was prepared in two steps from 28. The 4-hydroxybutyl ether 31 was accessible from 2 and 1,4-dibromobutane. The hydroxy group of 11 was converted to the tosylate 32. Base treatment of 32 led to the bicyclic [3(R) morpholinecarboxylic acid]8-cyclosporin (39). The [2-ethoxy-5 morpholinecarboxylic acid]8-cyclosporin 40 was prepared via 36. Base treatment of the bromoacetate 37 gave the morpholinone derivative 41. [4(R) Oxazolidinecarboxylic acid]8-cyclosporin (42) was obtained from 2 and methylene bromide. From 24 the tosylate 38 was prepared and cyclized to the hexahydrooxazepine derivative 43. [2(R)- Piperidinecarboxylic acid]8-cyclosporin (49) was prepared from 42 and 2(R)-piperidinecarboxylic acid 45 via 46-48. The bicyclic cyclosporin 39 was found to be about 3-4 times more active than cyclosporin A in our in vitro tests. PMID- 7783118 TI - Prodrugs of nitroxyl as potential aldehyde dehydrogenase inhibitors vis-a-vis vascular smooth muscle relaxants. AB - The synthesis and the chemical/biological properties of N-hydroxysaccharin (1) (2 hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide), a nitroxyl prodrug, are described. When treated with 0.1 M aqueous NaOH, 1 liberated nitroxyl (HN=O), a known inhibitor of aldehyde dehydrogenase (AlDH), in a time-dependent manner. Nitroxyl was measured gas chromatographically as its dimerization/dehydration product N2O. Under these conditions, Piloty's acid (benzenesulfohydroxamic acid) also gave rise to HNO. However, whereas Piloty's acid liberated finite quantities of nitroxyl when incubated in physiological phosphate buffer, pH 7.4, formation of nitroxyl from 1 was minimal. This was reflected in the differential inhibition of yeast AlDH (IC50 = 48 and > 1000 microM) and the differential relaxation of preconstricted rabbit aortic rings in vitro (EC50 = 1.03 and 14.0 microM) by Piloty's acid and 1, respectively. The O-acetyl derivative of 1, viz., N acetoxysaccharin (13a), was much less active in both assays. It is concluded that N-hydroxysaccharin (1) is relatively stable at physiological pH and liberates nitroxyl appreciably only at elevated pH's. As a consequence, neither 1 nor its O methyl (8a) and O-benzyl (8b) derivatives were effective AlDH inhibitors in vivo when administered to rats at 1.0 mmol/kg. PMID- 7783119 TI - Carbethoxylating agents as inhibitors of aldehyde dehydrogenase. AB - N,O-Dicarbethoxy-4-chlorobenzenesulfohydroxamate (1c) and O-carbethoxy-N hydroxysaccharin (6), both potential carbethoxylating agents, inhibited yeast aldehyde dehydrogenase (AlDH) with IC50's of 24 and 56 microM, respectively. The esterase activity of the enzyme was commensurably inhibited. AlDH activity was only partially restored on incubation with mercaptoethanol (20 mM) for 1 h. On incubation with rat plasma, 1c liberated nitroxyl, a potent inhibitor of AlDH. Under the same conditions, nitroxyl generation from 6 was minimal, a result compatible with a previous observation that nitroxyl generation from N hydroxysaccharin (7), the product of the hydrolysis of the carbethoxy group of 6, was minimal at physiological pH. Since chemical carbethoxylating agents represented by the O-carbethoxylated N-hydroxyphthalimide, 1 hydroxybenzotriazole, and N-hydroxysuccinimide (8, 9, and 10, respectively) likewise inhibited yeast AlDH, albeit with IC50's 1 order of magnitude higher, we postulate that 1c and 6 act as irreversible inhibitors of AlDH by carbethoxylating the active site of the enzyme. PMID- 7783120 TI - Use of medium-sized cycloalkyl rings to enhance secondary binding: discovery of a new class of human immunodeficiency virus (HIV) protease inhibitors. AB - A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9), conformationally-flexible, alkyl rings, the enzyme inhibitory activity of the resulting compounds was dramatically improved, and inhibitors with more than 50 fold better binding (e.g., 5d, Ki = 0.015 microM) were obtained. X-ray crystal structures of these inhibitors complexed with HIV protease indicated the cycloalkyl rings were able to fold into the S1' pocket of the enzyme and fill it much more effectively than the rigid benzene ring of the 4-hydroxycoumarin compound. This work has resulted in the identification of a promising lead structure for the design of potent, deliverable HIV protease inhibitors. Compound 5d, a small (MW = 324), nonpeptidic structure, has already shown several advantages over peptidic inhibitors, including high oral bioavailability (91 99%), a relatively long half-life (4.9 h), and ease of synthesis (three steps). PMID- 7783122 TI - Studies on the monoamine oxidase (MAO)-catalyzed oxidation of phenyl-substituted 1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine derivatives: factors contributing to MAO-A and MAO-B selectivity. AB - The structural parameters responsible for the substrate and inhibitor selectivities of the monoamine oxidases (MAO) A and B remain poorly understood. This situation has improved somewhat with structure-activity studies that have been performed on nuclear-substituted pargyline derivatives and 4-substituted 1 methyl-1,2,3,6-tetrahydropyridine derivatives. The results of these studies suggest that the active site of MAO-A is sterically more accommodating than the active site of MAO-B. In the present work we have undertaken a more systematic structure-substrate activity analysis with the aid of a series of 4 phenoxytetrahydropyridine analogs substituted at the para, meta, and ortho positions of the phenyl ring with chloro, methoxy, methyl, nitro, and phenyl groups. All of the compounds proved to be good substrates for both MAO-A and MAO B, and all were better MAO-A substrates than MAO-B substrates. The best defined structural parameter relating to selectivity again was the relatively better MAO A substrate properties of tetrahydropyridine derivatives bearing bulky C-4 substituents. Attempts to identify stereoelectronic effects related to substrate properties and selectivity with this series of compounds were not successful. Although some structural correlates with substrate activity can be made, overall the present state of knowledge is inadequate to provide good descriptors of structural features that characterize MAO-A and MAO-B substrates. PMID- 7783121 TI - Synthesis and biological evaluation of novel 2,6-diaminobenz[cd]indole inhibitors of thymidylate synthase using the protein structure as a guide. AB - The design, synthesis, and biochemical and biological evaluations of a novel series of 2,6-diaminobenz[cd]indole-containing inhibitors of human thymidylate synthase (TS) are described. The compounds are characterized by having either a pyridine or pyridazine ring in place of the (phenylsulfonyl)morpholinyl group of the known inhibitor N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2,6-diaminobenz[ cd]indole glucuronate (i). Active compounds from this series showed human TS inhibition constants below the 10 nM level and were potent, selective submicromolar antitumor agents in cell culture. The compounds were synthesized by reductive alkylation of a substituted 6-aminobenz[cd]indole or reductive cyclization of a substituted 1-cyano-8-nitronaphthalene. PMID- 7783123 TI - Synthesis, characterization, and antimalarial activity of the glucuronides of the hydroxylated metabolites of arteether. AB - The hydroxylated metabolites (log P 2.6-2.7) of beta-arteether (1) in rat liver microsomes that retain their endoperoxide moiety showed comparable in vitro antimalarial activity to that of the parent drug arteether (log P = 3.89). The search for analogs of artemisinin (7) more suitable for intravenous use led to the synthesis of the glucuronide conjugates of the phase I hydroxylated metabolites of arteether which were found to have good water solubility, yet retained moderate lipophilicity (log P = 0.6-1.8). While a strong correlation was observed between the log P value of the glucuronides, the phase I metabolites, and the parent compound, it was found that 9 beta-hydroxyarteetherglucuronide (26) was the most active and the most polar (log P = 0.61) of the glucuronides. While the in vitro antimalarial activity of 26 (IC50 = 89.3 ng/mL) was found to be much less than that for the parent compound, the activity of 26 was within a range that would have potential therapeutic use. PMID- 7783124 TI - Antimalarial activity of novel ring-contracted artemisinin derivatives. AB - Bromoacetal 2 undergoes a novel ring-contracted reaction to give the aldehyde 3 in the presence of DBU or triethylamine. The aldehyde 3 is reduced to the alcohol 4 and oxidized to the carboxylic acid 5. The alcohol 4 reacts with dihydroartemisinin to give the two diastereoisomers 38 and 39. All the compounds were tested for antimalarial activity in mice infected with chloroquine sensitive Plasmodium berghei. If the activity of a compound was comparable to that of the standard compound, such as arteether, it was tested against chloroquine resistant NS strain infection in mice. Initially the compounds were administered subcutaneously, and if found to be active, they were tested by oral route. The antimalarial activity of compounds 19, 38, and 39 was found to be comparable to that of arteether when tested in K-173-infected mice. They were also active against chloroquine resistant NS strain infection in mice. PMID- 7783125 TI - Hypoxia-selective antitumor agents. 10. bis(nitroimidazoles) and related Bis(nitroheterocycles): development of derivatives with higher rates of metabolic activation under hypoxia and improved aqueous solubility. AB - A series of analogues of the previously described compound N-[2-(2-methyl-5 nitroimidazol-1H-yl)ethyl]-4-(2-nitroimidazol- 1H-yl)butanamide (4), a novel hypoxic cell cytotoxin and radiosensitizer, have been prepared and evaluated for hypoxia-selective cytotoxicity and hypoxic cell radiosensitization in vitro. The new derivatives were designed to overcome the low aqueous solubility of 4 and its slow kinetics of killing under hypoxia. The nitroheterocycle unit had a significant effect on solubility, with 3-nitrotriazoles being about 6-fold more soluble than the corresponding 2-nitroimidazoles. Analogues with a range of neutral linker chains (polyhydroxy, alkanesulfonamide, and bisamide) showed only slightly improved solubility and were unable to be fully evaluated. However, a series of analogues with cationic amine linkers had adequate aqueous solubility (up to 280 mM). The amine analogues could not be prepared by direct reduction of precursor amides such as 4 and were most conveniently synthesized by aza-Wittig condensation of the appropriate azide and aldehyde components. The amine-linked compounds were more cytotoxic than 4, with the symmetrical bis(2-nitroimidazole) derivatives (13 and 14) up to 9-fold more potent. They showed hypoxic selectivities comparable to that of 4 (ca. 200-fold) but had much more rapid kinetics of killing under hypoxia, resulting in high hypoxic selectivity at early times in culture. The nature of the mechanism of cytotoxicity of these compounds remains unclear but appears not to be DNA cross-linking, with the compounds showing a lack of hypersensitivity toward repair-deficient UV4 cells. The enhanced solubility and hypoxia-selective cytotoxicity (at early times) of 13 compared with 4 represent significant potential advantages. PMID- 7783126 TI - N4-unsubstituted N1-arylpiperazines as high-affinity 5-HT1A receptor ligands. AB - In order to explore the structural requirements for high 5-HT1A affinity, a series of aryl-substituted N1-phenylpiperazines were synthesized and evaluated for their ability to displace [3H]-8-OH-DPAT from its specific binding sites in rat frontal cortex homogenates. We found 2-methoxy substitution to be favorable, while 4-methoxy substitution was detrimental for 5-HT1A affinity. Substitution with annelated rings at the 2,3-positions was highly favorable for all investigated compounds, with the exception of a pyrrole ring. All other substitutions, except fluoro, in this class of heterobicyclic phenylpiperazines decreased affinity in the order: ortho > para > meta. The loss of affinity in the ortho and para positions is probably due to steric factors: the substituents either cause steric hindrance with the receptor or prevent the compound from adopting the appropriate conformation for binding to the 5-HT1A receptor. Conformational analysis combined with structure-affinity relationships (SAR) indicates that our arylpiperazines may bind at the 5-HT1A receptor in a nearly coplanar conformation. Observed interactions of the compounds in our 5-HT1A receptor model appeared to be in agreement with SAR data. The aromatic part of the arylpiperazine moiety has pi-pi interactions with the aromatic residues Trp161 and Phe362 in helices IV and VI, respectively. The positively charged protonated basic nitrogen forms a hydrogen bond with the negatively charged Asp116 in helix III. The ammonium-aspartate complex is surrounded by aromatic residues Trp358 and Phe361 in helix VI. A lipophilic pocket is formed by Phe362, Leu366 (both helix VI), and the methyl group of Thr200 (helix V). In agreement with the model, addition of a methyl substituent to the structure of the benzodioxine analogue 12 in this region, yielding 13, is favorable for 5-HT1A receptor affinity. Unfavorable positions for substitution with bulky groups, like the 3- and 4-positions in the benzofuran compound 14, are explained by steric hindrance with the backbone atoms of helix V. Thus, we were able to rationalize the 5-HT1A SAR of existing N1-phenylpiperazines, as well as a series of newly synthesized bicyclic heteroarylpiperazines, in terms of receptor-ligand interactions. Several of these N4-unsubstituted compounds had affinities in the low-nanomolar range. PMID- 7783127 TI - Potent, orally active, competitive N-methyl-D-aspartate (NMDA) receptor antagonists are substrates for a neutral amino acid uptake system in Chinese hamster ovary cells. AB - A series of enantiomerically pure (phosphonomethyl)-substituted phenylalanine derivatives related to SDZ EAB 515 (1) were prepared as competitive N-methyl-D aspartate (NMDA) receptor antagonists. Unlike most known competitive NMDA antagonists, analogs in this series with the S-configuration are potent NMDA antagonists whereas analogs with the unnatural R-configuration are weak NMDA antagonists, as determined by receptor binding experiments and their anticonvulsant action in mice. Examination in a previously reported competitive NMDA pharmacophore model revealed that receptor affinity can be explained partially by a cavity that accommodates the biphenyl ring of 1, while the biphenyl ring of the R-enantiomer 2 extends into a disallowed steric region. We proposed that analogs with the natural S-configuration and a large hydrophobic moiety would have an advantage in vivo over analogs with an R-configuration by being able to use a neutral amino acid uptake system to enhance both peripheral adsorption and transport into the brain. Examination in a system L neutral amino acid transport carrier assay shows that 1 competes with L-Phe for transport in an apparent competitive and stereospecific manner (estimated Ki = 50 microM). The 1- and 2-naphthyl derivatives 3a,3b were found to be among the most potent, competitive NMDA antagonists yet discovered, being ca. 15-fold more potent than 1 in vitro and in vivo, with a long duration of action. The title compound 3a had potent oral activity in MES (ED50 = 5.0 mg/kg). 3a also retains its ability to compete, albeit more weakly than 1 (estimated Ki = 200 microM), for L-Phe uptake to CHO cells. In this series, analogs with the R-configuration are not substrates for the system L neutral amino acid transport carrier. These results provide evidence that central nervous system active agents can be designed as substrates of a neutral amino acid transporter as a means to enhance penetration of the blood-brain barrier. PMID- 7783128 TI - Cardioselective antiischemic ATP-sensitive potassium channel openers. 2. Structure-activity studies on benzopyranylcyanoguanidines: modification of the benzopyran ring. AB - The ATP-sensitive potassium channel (KATP) openers are of considerable interest as myocardial protecting agents. However, there exists a narrow window of safety for the use of first-generation compounds as antiischemic agents due to their powerful peripheral vasodilating effects, which can result in underperfusion of the area already at risk. We have recently disclosed the discovery of benzopyranylcyanoguanidine type KATP openers (BMS-180448) which are more selective for the ischemic myocardium compared to the first-generation compounds. This publication deals with structure-activity relationships for the antiischemic activity of the lead compound 8. The presence of an electron-withdrawing group at C6, an sp3 center at C4, and a gem-dimethyl group at C2 appears to be essential for antiischemic activity. Cyanoguanidine can be replaced with a urea moiety. The results reported here support the hypothesis that distinct structure-activity relationships exist for antiischemic and vasorelaxant activities of compounds related to 8 and cromakalim. The trifluoromethyl analog 10 is 550-fold more selective in vitro for the ischemic myocardium compared to the first-generation agent cromakalim. The reasons for the selectivity of these compounds for the ischemic myocardium are not clear at the present time. They may be related to the existence of receptor subtypes in smooth muscle and the myocardium. PMID- 7783129 TI - Three-dimensional quantitative structure-activity relationships of somatostatin analogues. 1. Comparative molecular field analysis of growth hormone release inhibiting potencies. AB - Somatostatin is a hypothalamic hormone that inhibits the release of growth hormone (GH). It has also been shown to inhibit the release of a broad range of hormones including insulin, glucagon, and gastrin. Presently, five different receptor subtypes of somatostatin have been characterized and cloned. Our previous work on the structure-activity relationship of somatostatin and that of many others has generated a large database of analogues with different biological activities and receptor affinities. This present work is an investigation of the growth hormone release-inhibiting potencies of somatostatin analogues by the three-dimensional quantitative structure-activity paradigm, comparative molecular field analysis (CoMFA). A total of 64 analogues were modeled in SYBYL using structural information from two NMR studies. The molecules were aligned by a root mean-square fit of atoms and field-fit of the steric and electrostatic molecular fields and the resulting databases analyzed by partial least squares analysis with cross-validation to extract the optimum number of components. The analysis was then repeated without cross-validation to give the final QSAR models. Preliminary investigations with the CoMFA models led to the synthesis of a new somatostatin analogue. This compound together with five other newly synthesized compounds not included in the original training sets were used to test the predictive ability of the CoMFA models. Two models with good predictive powers are presented. PMID- 7783131 TI - Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 1. 3-(omega-aminoalkyl)-1H-indoles. AB - A series of 4-(1H-indol-3-yl)-1-butyl-substituted 4-phenylpiperidines, 4-phenyl 1,2,3,6-tetrahydropyridines, and 4-phenylpiperazines was synthesized. The phenyl group was optionally substituted with 4-fluoro or 2-methoxy substituents. High affinity for both sigma 1 and sigma 2 binding sites was achieved with these compounds. Additionally, these compounds had relatively high affinity for serotonin 5-HT1A and 5-HT2A, dopamine D2, and adrenergic alpha 1 receptors. Introduction of a 4-fluorophenyl substituent at the indole nitrogen atom rendered very selective sigma 2 ligands with subnanomolar affinity for the sigma 2 binding site. The prototype of such a compound was 1-(4-fluorophenyl)-3-[4-[4-(4 fluorophenyl)-1-piperidinyl]-1-butyl]-1H- indole, 11a (code no. Lu 29-253). This compound had the following binding affinities: IC50 (sigma 1) = 16 nM, IC50 (sigma 2) = 0.27 nM, IC50 (5-HT1A) = 22,000 nM, IC50 (5-HT2A) = 270 nM, IC50 (D2) = 4200 nM, IC50 (alpha 1) = 220 nM. Spiro-joining of the phenyl and the piperidine rings into a spiro[isobenzofuran-1(3H),4'-piperdine] ring system resulted in even more selective compounds. Variations of the 1-substituent at the indole and of the chain length of the alkylene spacer group were studied. The optimal compound was the spiro analogue of compound 11a. This compound is 1'-[4 [1-(4-fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran- 1(3H),4' piperidine], 14f (code no. Lu 28-179), with the binding affinities: IC50 (sigma 1) = 17 nM, IC50 (sigma 2) = 0.12 nM, IC50 (5-HT1A) = 21,000 nM, IC50 (5-HT2A) = 2000 nM, IC50 (D2) = 800 nM, IC50 (alpha 1) = 330 nM. However, the most selective sigma 2 versus sigma 1 ligand was the tropane derivative 1-(4-fluorophenyl)-3-[4 [3-(4-fluorophenyl)-8-azabicyclo[3.2.1]oct-2- en-8-yl]-1-butyl]-1H-indole, 15a. This compound had the following binding affinities: IC50 (sigma 1) = 1200 nM, IC50 (sigma 2) = 2.5 nM. Potent anxiolytic activity in the black/white box exploration test in rats was found with the two most prominent sigma 2 ligands Lu 29-253 and Lu 28-179. Good penetration into the CNS was documented both after subcutaneous and peroral administration of Lu 28-179 by ex vivo binding studies. Long duration of action was demonstrated both in ex vivo binding (T1/2 approximately 20 h) and in the black/white box exploration test. PMID- 7783130 TI - Structure-activity relationships of milrinone analogues determined in vitro in a rabbit heart membrane Ca(2+)-ATPase model. AB - The cardiac activity of a series of analogues of the positive inotropic bipyridines amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) and milrinone (2-methyl 5-cyano-[3,4'-bipyridin]-6(1H)-one) was evaluated in vitro in a rabbit myocardial membrane Mg(2+)-dependent, Ca(2+)-stimulable adenosine triphosphatase (Ca(2+) ATPase) model and structure-activity relationships were compared for nine closely related derivatives. In the present studies, a 5-bromo analogue of milrinone stimulated myocardial membrane Ca(2+)-ATPase significantly (10(-7) M; P < 0.001 vs control, with 67% of the activity of milrinone), whereas a 2'-methyl-2H milrinone derivative was inactive. Although amrinone was inactive in this assay, its 2-methyl analogue was stimulatory. However, analogues lacking a 2-substituent (with or without a 5-cyano group) or with the 3-N position blocked by a methyl group did not stimulate myocardial membrane Ca(2+)-ATPase activity. Structural data for these bipyridines show that those with either a 2- or 2'-methyl substituent have a twist conformation, whereas those without are nearly planar. Activity data reveal that those bipyridines with a nonplanar conformation are more active in the Ca(2+)-ATPase assay. Further study of milrinone analogues with a 2'-methyl substituent shows that even though the effect on the twist angle is equivalent to that of 2-methyl substitution, these analogues are less potent. Data for this series reveal that the prerequisites for Ca(2+)-ATPase stimulation include not only a 2-methyl to maintain a twist conformation but also a free 3-N position and a 5-substituent. This model for optimal activity in the myocardial membrane Ca(2+)-ATPase system differs from those proposed for phosphodiesterase enzyme receptor recognition only in the requirement for a nonplanar molecule. We have previously shown that milrinone, but not amrinone, shares structural homology with thyroxine and was able to stimulate myocardial membrane Ca(2+) ATPase activity in a manner similar to the thyroid hormone. Additionally, milrinone, but not amrinone, was an effective competitor for thyroxine binding to the serum transport protein transthyretin. Analysis of the milrinone transthyretin crystal complex confirms the structural homology between milrinone and thyroid hormone which is not shared by amrinone. Modeling studies of the binding interactions of milrinone analogues indicate that the 2 desmethylmilrinone analogue, the most inhibitory analogue, lacks the hydrophobic contacts present in milrinone in its transthyretin-bound complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7783133 TI - Ocular delivery of the beta-adrenergic antagonist alprenolol by sequential bioactivation of its methoxime analogue. AB - Ocular delivery of alprenolol, a beta-adrenergic antagonist, by site-specific bioactivation of its methoxime analogue results in significant and prolonged decrease of the intraocular pressure in rabbits after topical administration. Alprenolone methoxime is stable in isotonic phosphate vehicle but undergoes enzymatic hydrolysis to the corresponding ketone in the eye. The ketone is then converted to alprenolol by a carbonyl reductase present in the iris-ciliary body. The benefit of this chemical delivery system approach includes the facile release of a potential antiglaucoma agent only at the site of the action; thus, unwanted systemic effects of the drug can be avoided. PMID- 7783132 TI - Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 2. Spiro-joined benzofuran, isobenzofuran, and benzopyran piperidines. AB - Spiro[isobenzofuran-1(3H),4'-piperidines] and the corresponding benzofuran and benzopyran derivatives have been synthesized and evaluated as sigma ligands. The compounds are related to Lu 28-179 (1'-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1- butyl]spiro[isobenzofuran-1(3H),4'-piperidine]) that has been demonstrated to be a selective sigma 2 ligand with affinity in the subnanomolar range. The object of the study was to determine the structural factors governing sigma 1/sigma 2 affinity and selectivity within this class of compounds. The N-substituent in spiro[isobenzofuran-1(3H),4'-piperidines] is highly important, both for affinity and selectivity. Spiropiperidines with no or small N-substituents (H, Me, Et) exert very low affinity for both sigma 1 and sigma 2 binding sites (IC50(sigma 1, sigma 2) > 100 nM), whereas medium-sized substituents (e.g., Pr, Bu, Ph(CH2)2) result in potent, but unselective compounds (IC50(sigma 1, sigma 2) = 2-5 nM). Increasing the chain length and the lipophilicity of the N-substituent result in compounds in which high affinity for sigma 2 binding sites is retained and with selectivity for sigma 2 vs sigma 1 binding sites (e.g., 4-cyclohexyl-1-butyl: IC50-(sigma 1) = 1.5 nM, IC50(sigma 2) = 0.07 nM). Introduction of substituents in the benzene ring of the spiro[isobenzofuran-1(3H),4'-piperidine] ring system of Lu 28-179 mainly affects affinity for sigma 1 binding sites. Compounds with substituents (F, CF3) in the 4- or 7-position of the isobenzofuran display high affinity for sigma 2 binding sites (IC50(sigma 2) = 0.5-2 nM) and very low affinity for sigma 1 binding sites (IC50(sigma 1) > 100 nM). Compounds with substituents (F, CF3, Me) in the 5- or 6-position of the isobenzofuran exert increased affinity for sigma 1 binding sites (IC50(sigma 1) = 5-30 nM, IC50(sigma 2) = 0.3-7 nM), thus rendering unselective compounds. Exchanging the isobenzofuran moiety of Lu 28-179 with thioisobenzofuran, benzofuran, or benzopyran also has a pronounced effect on both affinity and selectivity for sigma binding sites. The position of the oxygen atom and the position of the spiroconnection with the 4-position of the piperidine ring were varied, and only compounds in which both the benzene ring and the heteroatom are attached directly to the piperidine ring retain high affinity and selectivity for sigma 2 binding sites (e.g., 3,4-dihydro-1'-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1- butyl]spiro[1H-2-benzopyran-1,4'-piperidine]: IC50(sigma 1) = 53 nM, IC50(sigma 2) = 0.9 nM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7783134 TI - Ribozymes as human therapeutic agents. PMID- 7783135 TI - Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2 methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site. AB - In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 2-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2 methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low. PMID- 7783136 TI - Design and synthesis of new naphthalenic derivatives as ligands for 2 [125I]iodomelatonin binding sites. AB - New melatonin-like agents were designed from the frameworks of 2,5 dimethoxyphenethylamine, an important structural moiety for the 5-HT receptor, and (2-methoxynaphthyl)-ethylamine. The compounds were synthesized by classical methods and evaluated in binding assays with chicken brain membranes using 2 [125I]iodomelatonin as the radioligand. Preliminary studies on the series of N acyl-disubstituted phenethylamines showed the favorable role of the methoxy group in the ortho position of the side chain on the affinity for the receptor (Ki = 8 +/- 0.2 nM) for N-[2-(2-methoxy-5-bromophenyl)ethyl]propionamide (3o). This effect was confirmed in a series of the naphthalene derivatives, a bioisosteric moiety of the indole ring, and several potent ligands for melatonin binding sites were prepared such as N-[2-(2-methoxynaphthyl)ethyl]propionamide (4b) (Ki = 0.67 +/- 0.05 nM) and N-[2-(2,7-dimethoxynaphthyl)ethyl]cyclopropylformamide (Ki = 0.05 +/- 0.004 nM) (4k). Structure-activity relationships are discussed with regard to melatonin and bioisosteric naphthalenic compound 2. The Ki value for 4b was affected to a similar extent to that of melatonin by GTP-gamma-S or Mn2+ in competition experiments, suggesting an agonist profile for this compound. PMID- 7783137 TI - Application of the free energy perturbation method to human carbonic anhydrase II inhibitors. AB - An analysis of the free energy perturbation (FEP) method is presented that attempts to evaluate the efficacy of the FEP method in the drug discovery process. To accomplish this we have evaluated whether the FEP technique can accurately predict energetic and structural quantities relating to the inhibition of human carbonic anhydrase II (HCAII) by sulfonamides. Three well-characterized (both structurally and energetically) sulfonamide inhibitors of HCAII were examined in this study, 1a, 1b, and 1c. Results from FEP simulations on these compounds indicate that the FEP method can predict energetic trends reasonably well; however, the FEP method was less successful in reproducing detailed structural data. In particular, an expected movement of His-64 when inhibitor 1c was bound did not occur. We conclude that the FEP method can be used to determine relative free energies of binding but cannot be relied upon to reproduce subtle geometric changes. PMID- 7783138 TI - Investigation of the configurational and conformational influences on the hormonal activity of 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines and of their platinum(II) complexes. 1. Synthesis, estradiol receptor affinity, and estrogenic activity of diastereomeric [N-alkyl- and N,N'-dialkyl-1,2- bis(2,6 dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes. AB - N-Monoalkylated (Et) and N,N'-dialkylated (Me and Et) 1,2-bis(2,6-dichloro-4 hydroxyphenyl)-ethylenediamines and their dichloroplatinum(II) complexes were synthesized, and their configuration and conformational behavior were 1H-NMR spectroscopically clarified. The latter was brought in relation to their relative binding affinity (RBA) to the estrogen receptor as well as to their estrogenic potency. In contrast to the RR/SS-configurated diamines, the R/S-configurated ones showed marked estrogenic properties which correlate with the RBA's. In the related R/S-configurated complexes the estrogenic activity is determined by the same structural requirements as in the diamine series. However, a correlation between RBA's and estrogenic potencies is missing. The connection between spatial structure and activity is discussed by use of a drug-receptor model recently proposed by Holtje and Dall. PMID- 7783139 TI - Receptor surface models. 1. Definition and construction. AB - A receptor site model is a hypothetical model that characterizes the putative active site of a receptor. This paper describes a type of receptor site model called a receptor surface model, which is based on the construction of surfaces to represent spatial and electrostatic properties of the receptor active site. A receptor surface model is visually intuitive and is modifiable as the hypothesis is refined. It allows computations comparable to those that can be performed with traditional atomistic models. Structures can be energy minimized within the receptor surface model to arrive at conformations that are consistent with the model, and interaction energies can be estimated. Such calculations facilitate the evaluation of new candidate structures and provide a means to assess the predictive ability of a model. PMID- 7783140 TI - Receptor surface models. 2. Application to quantitative structure-activity relationships studies. AB - A new technique for using receptor surface models in quantitative structure activity relationship (QSAR) analysis is described. Receptor surface models provide compact, quantitative descriptors which capture three-dimensional information about putative receptor/ligand interactions. Receptor surface models can be constructed quickly, which allows the construction of multiple plausible models; a variable selection technique such as genetic function approximation (GFA) can then be used to suggest which receptor surface models provide the most valuable descriptors for QSAR. Advantages of this approach are shown by applying it against two previously-published and well-studied QSAR data sets. Our results indicate that the approach can model data as effectively as established 3D-QSAR techniques. PMID- 7783141 TI - Pyridyl-substituted tetrahydrocyclopropa[a]naphthalenes: highly active and selective inhibitors of P450 arom. AB - The synthesis and biological evaluation of substituted exo-1-(4-pyridyl) 1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalene s as inhibitors of estrogen biosynthesis is described [H (1); 4-OCH3 (2); 5-OCH3 (3); 6-OCH3 (4); 1-CH3, 6 OCH3 (5); 4-OCH3, 7-Br (6); 6-OCH3, 5-Br (7); 4-OH (8); 5-OH (9); 6-OH (10)]. The synthetic key step--the formation of the cyclopropyl ring--was accomplished using the conditions of a modified Wolff-Kishner reduction (N2H5OH/KOH; delta T) and yielded exclusively the exo-configurated diastereomers. The racemic compounds 1 10 showed an inhibition of human placental aromatase (P450 arom) exhibiting relative potencies (rp) from 3.7 to 303 (compounds 8 and 4, respectively; rp of aminoglutethimide (AG) identical to 1, fadrozole = 359). The enantiomers of 4 and 7 were separated by LPLC on tribenzoyl cellulose and by crystallization of the diastereomeric tartrates (4). (1aS,2S,7bS)-(+)-4 (absolute configuration determined by X-ray crystallographic analysis) is the active P450 arom inhibiting enantiomer of 4 and shows a rp value of 617. Compound 4 is a reversible inhibitor showing a competitive type of inhibition and a type II difference spectrum. In vitro 4 influenced other steroidogenic P450 enzymes either not at all (bovine adrenal P450 scc) or only marginally (rat testicular P450 17, bovine adrenal P450 18). In ACTH-stimulated rat adrenal tissue, 4 was less active, inhibiting corticosterone and aldosterone formation compared to AG and fadrozole, respectively. In vivo 4 was not superior to AG as far as the inhibition of the uterotrophic activity of androstenedione (juvenile SD rats) and the reduction of the plasma estradiol concentration (pregnant mares' serum gonadotropin-primed SD rats) are concerned. Compound 4 shows marked antitumor activity in the dimethylbenzanthracene-induced mammary carcinoma of the SD rat: in the postmenopausal model it is at least as active as AG; in the premenopausal experiment it is clearly superior to AG. No induction of hepatic P450 enzymes was observed in the latter experiment. The rp value of 4 toward rat ovarian P450 arom, i.e., 23 (rp of AG identical to 1), is markedly decreased compared to the human enzyme (rp value of 303). From this fact it must be concluded that 4 should be more active in the human than in the rat. PMID- 7783142 TI - Synthesis and cytotoxicity of novel lignans. AB - In this study the syntheses of 11 novel lignans are described. Their cytotoxicities are studied in GLC4, a human small cell lung carcinoma cell line, using the microculture tetrazolium (MTT) assay. Ten of these compounds were substituted with a menthyloxy group on the 5-position of the lactone. These compounds can easily be prepared in (novel) 'one-pot', three- or four-step syntheses. In addition, methods for controlling the stereogenic centers are described. Furthermore, five naturally occurring podophyllotoxin-related compounds were tested. The cytotoxicities of all lignan compounds, and of three non-lignan intermediates originating from the syntheses, were compared with the clinically applied anticancer agents etoposide, teniposide, and cisplatin. Most compounds showed moderate to high activities against GLC4, and two of the compounds containing a menthyloxy group showed activities comparable to the reference cytotoxic agents. PMID- 7783143 TI - Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle. AB - Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P1' side chains were suitable; omission of the P1' side chain seriously diminished potency. In the P2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b, d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP. PMID- 7783144 TI - Development of a novel series of trialkoxyaryl derivatives as specific and competitive antagonists of platelet activating factor. AB - The synthesis and structure-activity relationship (SAR) analysis of a novel series of trialkoxyaryl derivatives, as specific and competitive inhibitors of platelet activating factor (PAF), are described. Molecular modeling comparisons of PAF with the known antagonists Ginkgolide B and L-652731 led to the selection of N-[2-[(3,4,5-trimethoxybenzoyl)oxy]ethyl]-N,N,N-trimethylammonium iodide (1) from the Wellcome registry of compounds and to the synthesis of the lead compound N-[2-[[4-(hexyloxy)-3,5-dimethoxybenzoyl]oxy]ethyl]-N,N,N- trimethylammonium iodide (3, pKb 5.43). Further SAR considerations directed the design to 2 (hexyloxy)-1,3-dimethoxy-5-[4-(4-methylthiazol-5-yl)butyl] benzene (38) (pKb 7.14), a novel, specific, and competitive inhibitor of the PAF receptor in rabbit washed platelets. PMID- 7783145 TI - Immunospecific reduction of antioligonucleotide antibody-forming cells with a tetrakis-oligonucleotide conjugate (LJP 394), a therapeutic candidate for the treatment of lupus nephritis. AB - A discrete tetravalent conjugate, 7a (LJP 394), consisting of four oligonucleotides attached to a common carrier or platform was prepared. Single stranded oligonucleotide 20-mers consisting of alternating deoxycytidine deoxyadenosine nucleotides, (CA)10, were attached to a tetrabromoacetylated platform by displacement with sulfhydryl-terminated linkers. The tetrabromoacetylated platform 3a was synthesized in three steps using triethylene glycol bis-(chloroformate). The single-stranded conjugate was characterized by polyacrylamide gel electrophoresis, DNA sequencing, phosphate analysis, carbon and nitrogen combustion analysis, and correlation of stoichiometry to conversion in the conjugation process. HPLC and capillary electrophoretic methods were developed to evaluate purity. The tetrakis, single-stranded conjugate was annealed with a stoichiometric amount of a complementary single-stranded oligonucleotide 20-mer consisting of alternating thymidine-deoxyguanosine nucleotides, (TG)10. The double-stranded conjugate LJP 394 was characterized by melt temperature and hyperchromicity, phosphate analysis, and carbon and nitrogen combustion analysis. LJP 394 inhibits binding of DNA to anti-double-stranded oligonucleotide antibodies and reduces anti-oligonucleotide-specific plaque (antibody)-forming cells in an immunized mouse model by a proposed mechanism involving cross-linking B cell surface immunoglobins. PMID- 7783146 TI - Synthesis and biological evaluation of a series of new parenteral optically active 3-[[(N-alkylpyridinium-4'-yl)thio]methyl]-2-oxaisocephems. AB - The preparation and biological evaluation of a series of 7-[2-(2-aminothiazol-4 yl)-2-(Z)-[(cyclopentyloxy)imino]acetamido] optically active 2-oxaisocephems, substituted at the 3-position with [(N-alkylpyridinium-4'-yl)thio]methyl groups, are described. The resulting family of parenteral compounds displays a broad spectrum of in vitro antibacterial activity. These compounds exhibit increased activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis which are resistant to most cephalosporins with a similar level of Gram-negative activity to that of the third-generation antibiotics. In vivo efficacy of new antibacterial agents in this investigation is excellent against both Gram-positive and Gram-negative bacteria as compared with reference compounds. The in vitro and in vivo antimicrobial activity and the structure-activity relationships are presented. PMID- 7783147 TI - Novel 2,4-diamino-5-substituted-pyrrolo[2,3-d]pyrimidines as classical and nonclassical antifolate inhibitors of dihydrofolate reductases. AB - Eight novel, nonclassical, antifolate 2,4-diamino-5-(anilinomethyl)pyrrolo[2,3 d]pyrimidines, 1-8, with 3',4',5'-trimethoxyphenyl, 3',4'-dimethoxyphenyl, 2',5' dimethoxyphenyl, 4'-methoxyphenyl, 2',5'-diethoxyphenyl, 3',4'-dichlorophenyl, 1'naphthyl, and phenyl substituents were synthesized as potential inhibitors of dihydrofolate reductases (DHFRs). The classical analogue N-[4-[N-[(2,4 diaminopyrrolo[2,3-d]pyrimidin- 5-yl)methyl]amino]benzoyl]-L-glutamic acid (9) was also synthesized as an inhibitor of DHFR and an antitumor agent. The classical and nonclassical analogues were obtained via reductive condensations of the key intermediate 2,4-diamino-5-cyanopyrrolo[2,3-d]pyrimidine (12) with the appropriate substituted aniline or (p-aminobenzoyl)-L-glutamate followed by reduction of the intermediate Schiff bases with NaCNBH3. Compounds 1-9 were evaluated in vitro as inhibitors of rat liver (rl), Pneumocystis carinii (pc), and Toxoplasma gondii (tg) DHFRs. The nonclassical analogues were significantly selective against tgDHFR (vs rat liver DHFR), ranging from 7- to 92-fold. The inhibitory activity was lower in pcDHFR and rlDHFR (IC50s > 10(-5) M) than in tgDHFR (IC50s = 10(-6) M). The classical analogue had inhibitory activity similar to that of methotrexate (MTX) against the growth of human leukemia CCRF-CEM, A253, and FaDu squamous cell carcinoma (SCC) of the head and neck cell lines. Further evaluation of 9 against CCRF-CEM and its sublines having defined mechanisms of MTX resistance demonstrated that the analogue utilizes the reduced folate/MTX-transport system and primarily inhibits DHFR and poly-gamma glutamylation plays a role in its mechanism of action. Compound 9 was found to be 3-fold more efficient than aminopterin as a substrate for human folylpolyglutamate synthetase. PMID- 7783148 TI - Comparison of the protonation of isophosphoramide mustard and phosphoramide mustard. AB - The alkylating agent isophosphoramide mustard (IPM) spontaneously forms a relatively stable aziridine derivative which can be directly observed using NMR spectroscopy. The protonations of IMP and its aziridine were probed using 1H, 31P, 15N, and 17O NMR spectroscopy. The positions of the 31P, 15N, and 17O resonances of IPM between pH 2 and 10 each exhibit a single monobasic titration curve with the same pKa of 4.31 +/- 0.02. On the basis of a comparison with other compounds and our earlier work with phosphoramide mustard, the NMR results for IPM indicate that protonation occurs at nitrogen and not oxygen. Over this same pH range, each of the 1H, 31P, and 15N resonances of IPM-aziridine also show a single monobasic titration with a pKa of 5.30 +/- 0.09. The magnitude of the change in chemical shifts suggests that the protonation of the IPM-aziridine occurs at the ring nitrogen. Theoretical gas-phase calculations of PM, IPM, and IPM-aziridine suggest O-protonation to be more likely; however, aqueous phase calculations predict the N-protonated forms to be most stable. Furthermore, for PM and IPM-aziridine, which contain nonequivalent nitrogens, the theoretical calculations and experimental data both agree as to which nitrogen undergoes protonation. These results suggest that the IMP-aziridine remains unprotonated under physiological conditions and may, in part, explain the lower alkylating activity of IPM as compared to PM. PMID- 7783149 TI - Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice. AB - Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2 (N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application. PMID- 7783150 TI - Annulated heterocyclic bioisosteres of norarecoline. Synthesis and molecular pharmacology at five recombinant human muscarinic acetylcholine receptors. AB - A series of O-alkylated analogs of 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3 ol (THAO) were synthesized and characterized as ligands for muscarinic acetylcholine receptors (mAChRs). O-Methyl-THAO (4a), O-ethyl-THAO (4b), O isopropyl-THAO (4c), and O-propargyl-THAO (4d) were shown to be potent inhibitors of the binding of tritiated quinuclidinyl benzilate (QNB), pirenzepine (PZ), and oxotremorine-M (Oxo-M) to tissue membrane preparations. In the [3H]-Oxo-M binding assay, receptor affinities in the low nanomolar range were measured for 4a (IC50 = 0.010 microM), 4b (IC50 = 0.003 microM), 4c (IC50 = 0.011 microM), and 4d (IC50 = 0.0008 microM). Pharmacological effects (EC50 or Ki values) and intrinsic activities (per cent of maximal carbachol responses) were determined using five recombinant human mAChRs (m1-m5) and the functional assay, receptor selection and amplification technology (R-SAT). Compound 4c antagonized carbachol-induced responses at m1, m3, and m5. With the exception of 4b, which was an antagonist at m5, 4a,b,d showed partial agonism at m1-m5 with very similar subtype selectivity (m2 > m4 > m1 > or = m3 > m5). Agonist index values for 4a-d, which were calculated from [3H]QNB (brain) and [3H]Oxo-M (brain) binding data, were shown to be predictive of pharmacologically determined intrinsic activities at m1-m5, the same rank order of intrinsic activity being observed at all five mAChRs (4a > 4d > 4b > 4c). It is concluded that within this class of high-affinity mAChR (m1-m5) ligands, containing secondary amino groups, minor changes of the bioisosteric ester alkyl groups have marked effects on potency and, in particular, intrinsic activity. PMID- 7783151 TI - Synthesis of some 2-aryl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones as tools to define the essential pharmacophoric descriptors of a benzodiazepine receptor ligand. AB - The synthesis and benzodiazepine receptor (BZR) affinity of some 1,2,4 triazolo[1,5-c][1,3]benzoxazin-5-ones, 2-22, are reported. Compounds 2-22 are devoid of the proton donor group, which according to a BZR schematic model was one of the pharmacophoric descriptors for receptor-ligand interaction. The binding data show that 2-(2-fluorophenyl)-9-chloro-1,2,4-triazolo[1,5 c][1,3]benzoxazin-5 -one (12) and some other compounds display nanomolar BZR affinity, indicating that the hydrogen donor group is not essential for the anchoring of 6,6,5-tricyclic systems to the BZR but only affects the potency of a ligand. PMID- 7783152 TI - Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes. AB - A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8 (dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5 HT1D alpha than for 5-HT1D beta receptors. PMID- 7783154 TI - Irreversible inhibitors of nicotinic acetylcholine receptors: isolation and structural characterization of the biologically active solvolysis products of bipinnatin-A and bipinnatin-C. AB - The lophotoxins irreversibly inhibit nicotinic acetylcholine receptors by covalent modification of Tyr190 in the alpha-subunits of the receptor. Previous studies have shown that the naturally occurring lophotoxin analogs bipinnatin-A, B, and -C are actually inactive protoxins and that their ability to irreversibly inhibit nicotinic receptors is enhanced by preincubation in buffer. However, the ability of lophotoxin to irreversibly inhibit nicotinic receptors does not appear to be enhanced by preincubation in buffer. These observations led to the current effort to isolate and determine the structures of biologically active bipinnatins. Disappearance of the lophotoxins from solution followed a simple first-order exponential decay function. Lophotoxin, however, was approximately 40 fold more stable then bipinnatin-A, -B, or -C. Solvolysis of the bipinnatins, but not of lophotoxin, resulted in production of an equimolar amount of acetic acid at a rate similar to the rate of solvolysis, suggesting that the initial event in solvolysis of these toxins involves hydrolysis of an acetate ester. Proton NMR and fast-atom bombardment mass spectroscopy were used to confirm the structures of the active solvolysis products of bipinnatin-A and -C. Their structures and the relative pH insensitivity of the solvolysis reaction suggest that biological activation of the bipinnatins may proceed through an SN1 type of substitution reaction involving elimination of acetate followed by reaction of a carbocation intermediate with solvent. PMID- 7783153 TI - Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H benz[e]indole ring system. 2. Effects of 8-amino nitrogen substitution on serotonin receptor binding and pharmacology. AB - A series of analogs of the potent and selective 5-HT1A agonist 8-(di-n propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (2b) (OSU191) was prepared in which the dipropylamino group was modified to bear a variety of substituents. These compounds were evaluated for both in vitro and in vivo effects, including the establishment of a receptor binding profile for these analogs at the 5-HT1A, dopamine D-2, dopamine D-3, 5-HT1D alpha, and 5-HT1D beta sites. Several of the analogs were evaluated for their biochemical effects in reserpinized rats, specifically with regard to in vivo changes in brain levels of 5-HTP and DOPA. Nearly all of the compounds prepared for this study were exceedingly potent at the 5-HT1A receptor, although most also displayed significant affinity for the dopamine D-2 receptor. A strong preference for the 5 HT1D alpha over the 5-HT1D beta receptor was also apparent. An analog bearing a butylglutarimide side chain, S-7k, was extremely selective for the 5-HT1A receptor. Although this compound possessed a Ki of 0.6 nM, it elicited only modest changes in 5-HTP brain levels. However, this compound did not appear as an antagonist when tested in a cyclic-AMP-based intrinsic activity assay. PMID- 7783155 TI - Identification of 3,5-dihydro-2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones as novel high-affinity glycine site N-methyl-D-aspartate antagonists. AB - Almost all of the existing known antagonists at the glycine site of the N-methyl D-aspartate (NMDA) receptor have a low propensity for crossing the blood-brain barrier. It has been suggested that in many cases this may be due to the presence of a carboxylic acid which is a common feature of most of the potent full antagonists at this receptor. In this study, 2-aryl-1H-pyrazolo[3,4-c]quinoline 1,4(2H)-diones were found to have high-affinity binding at the glycine receptor. In particular, structure-activity studies identified 7-chloro-3,5-dihydro-2-(4 methoxyphenyl)-1H-pyrazolo[3,4-c]quinoline- 1,4(2H)-dione as the most potent of a series of analogues with an IC50 of 3.3 nM. The measured pKa values in this class of compounds (typically 4.0) indicate they are of equivalent acidity to carboxylic acids. Functional antagonism was demonstrated by inhibition of NMDA evoked responses in rat cortical slices. Anticonvulsant activity in DBA/2 mice was achieved after dosing by direct injection into the cerebral ventricles, but no activity was seen after systemic administration, suggesting low brain penetration with this class of antagonists. PMID- 7783156 TI - New analogs of burimamide as potent and selective histamine H3 receptor antagonists: the effect of chain length variation of the alkyl spacer and modifications of the N-thiourea substituent. AB - Burimamide was one of the first compounds reported to antagonize the activation of the histamine H3 receptor by histamine. We have prepared a large series of burimamide analogs by variation of the alkyl spacer length of burimamide from two methylene groups to six methylene groups and also by replacement of the N-methyl group with other alkyl and aryl groups. All analogs are reversible, competitive H3 antagonists as determined on the guinea pig intestine. Elongation of the alkyl chain from an ethylene chain to a hexylene chain results in an increase of the H3 antagonistic activity. The H3 selective pentylene and hexylene analogs of burimamide are about 10 times more potent than burimamide. The N-thiourea substituents, however, have no beneficial influence on the affinity. PMID- 7783157 TI - 2-Phenyl-4-(aminomethyl)imidazoles as potential antipsychotic agents. Synthesis and dopamine D2 receptor binding. AB - A series of 2-phenyl-4-(aminomethyl)imidazoles were designed as conformationally restricted analogs of the dopamine D2 selective benzamide antipsychotics. The title compounds were synthesized and tested for blockade of [3H]YM-09151 binding in cloned African green monkey dopamine D2 receptor preparations. The binding affinity data thus obtained were compared against that of the benzamides and a previously described series of 2-phenyl-5-(aminomethyl)-pyrroles. PMID- 7783158 TI - Application of 15N nuclear magnetic resonance spectroscopy to the determination of the stability of aryl nitrogen mustards. AB - An excellent correlation has been shown to exist between the 15N NMR chemical shifts of a series of aryl nitrogen mustards and the Hammett constant, sigma, which is much improved by the use of sigma-. These chemical shifts also correlate well with the hydrolysis rates of the compounds in 50% aqueous acetone at 66 degrees C and their alkylation of 4-(4'-nitrobenzyl)pyridine under similar conditions. Thus 15N NMR is a straightforward and material-conserving method for estimating the relative stabilities of aryl nitrogen mustards. PMID- 7783159 TI - Effects of tubercidin and its 5'-O-methyl ether on adenosine receptors and mediator release functions in mast cells. AB - Tubercidin (7-deazaadenosine, Tu) is a highly cytotoxic nucleoside xenobiotic that, as the nucleoside or nucleotide derivatives, closely mimics the actions of adenosine (or its corresponding nucleotides) in a wide variety of biochemical/biological systems. In light of its acceptance in these test systems as an adenosine (Ado) surrogate, it was postulated that the compound might interact with adenosine receptors. To test this hypothesis, a nonphosphorylatable derivative (5'-O-methyl tubercidin, MeTu) was prepared and evaluated in comparison with tubercidin and Ado in a variety of biological systems. In a cell culture assay using Chinese hamster ovary cells, MeTu is approximately one-third as cytotoxic as is Ado and 10(5)-fold less cytotoxic than Tu. Both Tu and MeTu inhibited the antigen-stimulated release of beta-hexosaminidase from mouse bone marrow derived mast cells in vitro, but only Tu was active in the in vivo PCA test. The inhibitory effect of MeTu on mast cell mediator release does not appear to involve interaction with adenosine receptors or to be the result of conversion to Tu per se. PMID- 7783160 TI - Synthesis and biological evaluation of novel C-4 aziridine-bearing paclitaxel (taxol) analogs. AB - Three novel C-4 aziridine-bearing paclitaxel analogs, 3-5, have been synthesized during the course of our continuing effort at C-4 modification. The key step in the synthesis is the aziridine ring formation at the C-4 position via an intramolecular Mitsunobu reaction. The syntheses and the biological evaluation of these C-4 aziridine-containing derivatives are herein discussed. PMID- 7783161 TI - Genetic testing for cancer predisposition: need and demand. PMID- 7783162 TI - FRAXE and mental retardation. AB - Mental impairment and instability of the CCG repeat at FRAXE is described in six kindreds. Cosegregation of FRAXA and FRAXE was found within one of these kindreds. Cytogenetic expression of FRAXE was shown to skip a generation when associated with a reduction in size of the CCG expansion when transmitted through a male; however, in general, transmission occurred through females and a copy number increased from one generation to the next. In these respects the behaviour of FRAXE paralleled that of FRAXA. A relationship between FRAXE and non-specific mental impairment is strongly suggested by the occurrence in these families of more mentally impaired male and female carriers, after removal of index cases, than could reasonably be expected by chance. PMID- 7783163 TI - A rapid, non-radioactive screening test for fragile X mutations at the FRAXA and FRAXE loci. AB - Screening of referrals for the mutations associated with the fragile X syndrome constitutes a significant workload in many genetics laboratories. Since the great majority of these referrals will be negative, there is a need for a rapid and inexpensive screening test. We have developed an assay which allows simultaneous amplification of the triplet repeat sequences at the FRAXA and FRAXE loci by polymerase chain reaction, and detection of the products on non-denaturing gels stained with ethidium bromide. Alleles of normal size are detected, leaving a small minority of samples to be tested by Southern blotting. A PCR based assay for detection of methylation at the CpG island upstream of the FMR-1 gene has also been devised. PMID- 7783164 TI - Saethre-Chotzen syndrome associated with balanced translocations involving 7p21: three further families. AB - We describe three families segregating different reciprocal chromosome translocations, t(7;18)(p21.2;q23), t(2;7)(q21.1;p21.2), and t(5;7)(p15.3;p21.2). A total of seven apparently balanced carriers have been identified and all manifest features of the Saethre-Chotzen syndrome, although only two have overt craniosynostosis. In one family the carriers are immediately recognisable by their unusual ears, and clefts of the hard or soft palate are present in all three families. These observations extend previous linkage and cytogenetic evidence that a locus for Saethre-Chotzen syndrome resides in band 7p21.2. PMID- 7783165 TI - A clinical, cytogenetic, and molecular study of 40 adults with the Prader-Willi syndrome. AB - A clinical, cytogenetic, and molecular study has been carried out on 40 adults with a firm diagnosis of Prader-Willi syndrome. A cytogenetically detectable deletion was observed in 58% while further subjects had a deletion which was detectable by molecular methods only, giving a total of 76%. Four cases of maternal uniparental disomy (UPD) were all female. Three of them were heterodisomic while the fourth was isodisomic. Two male probands were heterozygous at all loci tested yet did not have UPD. Although methylation studies showed that one of them had a single band using probe PW71, the other one had two bands. Psychiatric studies suggest that females with maternal UPD are indistinguishable psychologically from those with a paternal deletion in 15q11q13. PMID- 7783166 TI - Heterogeneity in Li-Fraumeni families: p53 mutation analysis and immunohistochemical staining. AB - We have screened two families for constitutional TP53 mutations, one family with Li-Fraumeni syndrome and the other with features of this syndrome. We report a germline mutation in exon 7 of the TP53 gene in the family with "Li-Fraumeni like" syndrome. The mutation occurred at codon 245 and causes a Gly-Ser amino acid change. It was inherited by both affected and unaffected subjects. Malignant tumours from all members of this family showed strong positive nuclear immunohistochemical staining with antibodies CM-1 and DO1, directed against TP53. In contrast, no constitutional TP53 mutations were found in a "classic" Li Fraumeni family. In this family positive staining was seen in both malignant and normal tissues. These results support previous findings that variants of the Li Fraumeni syndrome exist since not all LFS families carry TP53 germline mutations. Secondly, immunohistochemical positivity is not synonymous with an underlying mutation and is therefore inadequate as an exclusive diagnostic marker. PMID- 7783167 TI - Male neonatal death and progressive weakness and immune deficiency in females: an unknown X linked condition. AB - We report a family with an undiagnosed X linked condition. The grandmother, two of her three daughters, and one of her grand-daughters have a slowly progressive proximal weakness, brisk reflexes, poor bladder function, static reduced night vision, and IgG2 deficiency. The diagnosis of the three living symptomatic females was "hereditary spastic paraplegia plus". They have lost five male children who died in the neonatal period of severe hypotonia and were of low birth weight. Investigations have not led to a unifying diagnosis: myotonic dystrophy, NARP, and X linked hyper IgM were specifically eliminated. Using the hypothesis that the condition is X linked dominant, haplotype analysis of the family suggests that the disease locus is within Xq26-qter. This entity should be considered in the differential diagnosis of families presenting with severe neonatal hypotonia in males and females with symptoms suggestive of complex hereditary spastic paraplegia. PMID- 7783168 TI - A gene for familial venous malformations maps to chromosome 9p in a second large kindred. AB - Venous malformations are a common form of vascular anomaly that cause pain and disfigurement and can be life threatening if they involve critical organs. They occur sporadically or in a familial form, where multiple lesions are usually present. We have identified a large kindred showing autosomal dominant inheritance of venous malformations. Using this family we confirm linkage of a familial form of venous malformations to chromosome 9p. We suggest that blue rubber bleb naevus syndrome can be considered a particular manifestation of this form of familial venous malformations. The candidate region for this gene encompasses the interferon gene cluster and the MTS1 (p16) tumour suppressor gene. PMID- 7783170 TI - Further evidence for an intermittent pattern of neural tube closure in humans. AB - Evidence is presented to support the recent suggestion that human neural tube closure is similar to that observed in mice, and comprises several regionally distinct closure sites rather than being a simple zipping up process. Seven subjects, each with more than one neural tube defect (NTD), are described. Comparative studies of the location of the lesions in relation to the closed parts of the neural tube imply that such NTD could only have come about if there were intermittent closure of the neural tube. PMID- 7783169 TI - Absence of linkage between familial neural tube defects and PAX3 gene. AB - Neural tube defects (NTD) are among the most common and disabling birth defects. The aetiology of NTD is unknown and their genetics are complex. The majority of NTD cases are sporadic, isolated, nonsyndromic, and generally considered to be multifactorial in origin. Recently, PAX3 (formerly HuP2, the human homologue of mouse Pax-3), on chromosome 2q35-37, was suggested as a candidate gene for NTD because mutations of Pax-3 cause the mouse mutant Splotch (Sp), an animal model for human NTD. Mutations in PAX3 were also identified in patients with Waardenburg syndrome type 1 (WS1). At least eight patients with both WS1 and NTD have been described suggesting pleiotropy or a contiguous gene syndrome. Seventeen US families and 14 Dutch families with more than one affected person with NTD were collected and 194 people (50 affected) from both data sets were genotyped using the PAX3 polymorphic marker. The data were analysed using affecteds only linkage analysis. The lod scores were -7.30 (US), -3.74 (Dutch), and -11.04 (combined) at theta = 0.0, under the assumption of the autosomal dominant model. For the recessive model, the lod scores were -3.30 (US), -1.46 (Dutch), and -4.76 (combined) at theta = 0.0. Linkage between PAX3 and familial NTD was excluded to 9.9 cM on either side of the gene for the dominant model and to 3.63 cM on either side of the gene for the recessive model in the families studied. No evidence of heterogeneity was detected using the HOMOG program. Our data indicate that PAX3 is not a major gene for NTD. PMID- 7783172 TI - Menkes disease. PMID- 7783171 TI - Haplotype analysis in autosomal dominant polycystic kidney disease. AB - Haplotype analysis was performed in 35 autosomal dominant polycystic kidney disease (ADPKD) families typed with 13 markers close to the PKD1 locus. The identification of recombinants close to the PKD1 gene on chromosome 16p indicates that PKD1 lies between CMM65 distally and 26-6 proximally. In addition, three unlinked (PKD2) families and two families with potential new mutation were identified. PMID- 7783173 TI - Neonatal spinal muscular atrophy with diaphragmatic paralysis is unlinked to 5q11.2-q13. AB - Two sibs affected by the severe neonatal form of spinal muscular atrophy (SMA) with diaphragmatic paralysis are described. The two sibs were discordant for the haplotypes determined by DNA markers flanking the SMA locus. This supports non linkage of SMA to chromosome 5 in this family and indicates that the uncommon SMA type I variant associated with early onset respiratory failure maps outside the 5q11.2-q13.3 region. PMID- 7783174 TI - A mutation causing DHPR deficiency results in a frameshift and a secondary splicing defect. AB - In our analysis of mutations causing DHPR deficiency we identified a patient in whom there was an aberrant transcription pattern detected by PCR of DHPR cDNA. However, unlike the pattern observed as a result of most splicing mutations, there is some full length transcript. The mutation was located and is a single nucleotide deletion at position 570/571 of the DHPR cDNA sequence and results in a frameshift and premature termination after the addition of six amino acids. The mutation is present in a homozygous state in the patient and in a heterozygous state in both parents. The exon which is deleted at high frequency in the patient is the putative exon 4, which is remote from the mutation, and confirms our observation that exon 4 skipping is a relatively common event. PMID- 7783175 TI - Genetic refinement of the chromosome 5q lattice corneal dystrophy type I locus to within a 2 cM interval. AB - Lattice corneal dystrophy type I (LCDI) is a relatively common corneal dystrophy which can cause severe visual impairment. Recent studies have suggested a genetic localisation for the disease to chromosome 5q. Independent genetic linkage analysis in a six generation LCDI pedigree confirmed linkage to the 5q region bounded by marker loci IL9 and D5S436 suggesting genetic homogeneity. A maximum two point lod score of 7.51 (theta = 0.03) was obtained with marker D5S393. Multipoint and haplotype data positioned the disease between loci D5S393 and D5S396 corresponding to a genetic distance of 2cM, thus refining linkage sufficiently to allow for physical mapping of this disorder. PMID- 7783176 TI - Kabuki syndrome-like features in monozygotic twin boys with a pseudodicentric chromosome 13. AB - We present monozygotic twin boys with features of Kabuki syndrome. The twins were discordant for cleft palate and coarctation of the aorta. The occurrence of Kabuki syndrome in monozygotic twins has not been previously reported and reinforces the belief that this condition has a genetic basis. Chromosomal analysis on the boys showed a pseudodicentric chromosome 13 with an inactive centromere and satellite stalks at 13q12.11: 46,XY,psu dic(13)(13pter- >13q12.11::13p12-->13q11.00:: 13q12.11-->13qter). Their phenotypically normal mother appears to carry the same pseudodicentric chromosome 13. PMID- 7783177 TI - Assignment of microsatellite sequences to the region duplicated in CMT1A (17p12): a useful tool for diagnosis. AB - Charcot-Marie-Tooth disease type 1A (CMT1A), the most prevalent form of the peripheral hereditary neuropathies, has been associated with a duplication of a genomic segment of 1.5 Mb, located in 17p11.2. Recently, the same segment has been found to be deleted in patients with another peripheral neuropathy, hereditary neuropathy with liability to pressure palsies (HNPP). Highly polymorphic markers are rare in this area, rendering the diagnosis highly dependent either on invasive examinations (like nerve biopsy) or not totally reliable (like gene dosage). Thus, we used a contig of YACs, including the whole region duplicated in CMT1A, to map highly polymorphic microsatellite loci, designed in Genethon. We showed that four of these loci are located in the duplicated region, allowing us to propose them as diagnostic markers for CMT1A and HNPP. PMID- 7783178 TI - Renal tubular leakage complicating microcephalic osteodysplastic primordial dwarfism. AB - We describe a male infant with phenotypic and radiological features of microcephalic osteodysplastic primordial dwarfism type I/III. He showed severe osteoporosis and biochemical derangement owing to renal tubular leakage, which has not previously been reported in this condition. He died aged 5 months. PMID- 7783180 TI - Linkage refinement localises Sorsby fundus dystrophy between markers D22S275 and D22S278. AB - Sorsby fundus dystrophy is an autosomal dominant disorder which both clinically and histopathologically bears striking similarities to age related macular degeneration, one of the leading causes of blindness in the developed world. Recent studies have suggested a genetic localisation of the disease to chromosome 22q in a large genetic interval of approximately 25 cM. Independent genetic linkage analysis in a six generation British pedigree confirms linkage to the chromosome 22q region. A maximum two point lod score of 7.09 with no recombination was obtained with marker D22S280. Haplotype data positioned the disease between loci D22S275 and D22S278, thus significantly reducing the region on chromosome 22q where the gene is located. PMID- 7783179 TI - Unusual (CGG)n expansion and recombination in a family with fragile X and DiGeorge syndrome. AB - In a fragile X family referred for prenatal diagnosis, the female fetus did not inherit the full fragile X mutation from her mother, but an unexpected expansion within the normal range of CGG repeats from 29 to 39 was observed in the paternal X chromosome. Also, a rare recombination between DXS548 and FRAXAC1 was recorded in the maternal meiosis. Follow up of the neonate confirmed the same DNA genotype as in the CVS, but the child died of DiGeorge syndrome after four days and was subsequently found to carry a microdeletion of chromosome 22 using probe cEO. It is suggested that in this family the deletion of chromosome 22 is likely to be a chance event but the rare recombinant and the fragile X mutation might be causally related. PMID- 7783181 TI - Familial schizencephaly: further delineation of a rare disorder. AB - We report on two Somalian sibs with severe developmental retardation and spastic cerebral paresis. Both children have bilateral cerebral clefts in the Sylvian region with dilatation of the ventricles, absence of the septum pellucidum, and heterotopia. The diagnosis of familial schizencephaly was made. The occurrence of schizencephaly in two affected sibs supports a genetic basis for schizencephaly. PMID- 7783182 TI - Thalassaemia in Azerbaijan. PMID- 7783183 TI - Blepharophimosis-mental retardation syndrome and terminal deletion of chromosome 3p. PMID- 7783184 TI - Mechanism of image formation for thick biological specimens: exit wavefront reconstruction and electron energy-loss spectroscopic imaging. AB - With increasing frequency, cellular organelles and nuclear structures are being investigated at high resolution using electron microscopic tomography of thick sections (0.3-1.0 microns). In order to reconstruct the structures in three dimensions accurately from the observed image intensities, it is essential to understand the relationship between the image intensity and the specimen mass density. The imaging of thick specimens is complicated by the large fraction of multiple scattering which gives rise to incoherent and partially coherent image components. Here we investigate the mechanism of image formation for thick biological specimens at 200 and 300 keV in order to resolve the coherent scattering component from the incoherent (multiple scattering) components. Two techniques were used: electron energy-loss spectroscopic imaging (ESI) and exit wavefront reconstruction using a through-focus series. Although it is commonly assumed that image formation of thick specimens is dominated by amplitude (absorption) contrast, we have found that for conventionally stained biological specimens phase contrast contributes significantly, and that at resolutions better than approximately 10 nm, superposed phase contrast dominates. It is shown that the decrease in coherent scattering with specimen thickness is directly related to the increase in multiple scattering. It is further shown that exit wavefront reconstruction can exclude the microscope aberrations as well as the multiple scattering component from the image formation. Since most of the inelastic scattering with these thick specimens is actually multiple inelastic scattering, it is demonstrated that exit wavefront reconstruction can act as a partial energy filter. By virtue of excluding the multiple scattering, the 'restored' images display enhanced contrast and resolution. These findings have direct implications for the three-dimensional reconstruction of thick biological specimens, where a simple direct relationship between image intensity and mass density was assumed, and the aberrations were left uncorrected. PMID- 7783186 TI - Medical malpractice and doctor-patient communication. PMID- 7783185 TI - Electrophoretic transfer of protein-pigment complexes from non-denaturing gels to electron microscopy grids. AB - Different fractions of a mixture of protein-pigment complexes have been separated from one another by non-denaturing gel electrophoresis. These complexes were prepared for observation by inserting electron microscope grids directly into the focused bands of the pigment-protein complexes and resuming electrophoresis for a brief time, so that the complexes were deposited onto the grids. It was found that complexes deposited from each band exhibited distinctly different appearances. It was also found that the exact conditions of electrophoretic deposition onto the grids affected the appearance of the complexes. The protein pigment complexes were characterized additionally by spectroscopy and denaturing gel electrophoresis. PMID- 7783187 TI - Swimming in a pool of paper. PMID- 7783188 TI - Laryngeal carcinoma--a relationship to tobacco and alcohol use. PMID- 7783189 TI - Calcium chanel blockers safe, says UMC hypertension expert. PMID- 7783190 TI - Force-induced conformational change of bacteriorhodopsin. AB - The cytoplasmic surface topography of purple membranes imaged by the atomic force microscope depends mainly on the force applied to the stylus. Imaged at forces of 300 pN, individual bacteriorhodopsin molecules reveal two domains. The resulting donut-shaped trimers reversibly transform into structures exhibiting three prominent protrusions when scanned at 100 pN. In parallel, the height of the protein moiety above the lipid layer increases from 4 A to 6 A. From the known structure of bacteriorhodopsin it appears that this change may be related to a bending of the most prominent cytoplasmic loop. PMID- 7783191 TI - Conserved structural features on protein surfaces: small exterior hydrophobic clusters. AB - The extent to which side-chains at the surface of globular proteins adopt well defined conformations is a matter of some controversy and, in turn, the idea that specific interactions amongst them might make a significant contribution to defining tertiary structures would be generally seen as questionable. In at least some cases, however, there is evidence for organisation of the surface to form discrete, tightly packed clusters. In this paper we examine the role of such clusters in accommodating large, hydrophobic residues on the exterior of protein structures. Taking poplar plastocyanin as a detailed example, we find a variety of ways in which solvent accessibility of such non-polar groups can be limited and we highlight, in particular, a rather simple type of cluster in which a single hydrophobic residue is substantially excluded from solvent by a cage of surrounding, chiefly hydrophilic, side-chains. Comparison with the structures of a number of other proteins which share with plastocyanin the Greek key beta sandwich topology, but are otherwise unrelated, produces the remarkable finding that analogous clusters are commonly found in the topologically equivalent position. This suggests that these features, which we call small exterior hydrophobic clusters (SEHCs), may have an important structural role and we able that their recurrent position in these proteins is such that they may help to fix the register of non-sequential beta-strands and, perhaps, to specify their association during folding. Similar SEHCs can also be identified in other classes of protein structure and we give a four-helix bundle protein, the rop dimer, as an example. It seems likely that accommodation of large non-polar residues provides a mechanism for introducing a degree of local order in to the surface layers of proteins in solution and it is possible that this behavior could play a role in locking tertiary structures. Thus, while the packing of the hydrophobic core of a globular protein is surely the dominant driving force for folding, it may be that, in some cases at least, interactions among surface residues also play an important role in determining the fine details of the structure. PMID- 7783193 TI - Mechanism of post-segregational killing by hok-homologue pnd of plasmid R483: two translational control elements in the pnd mRNA. AB - The pnd system of plasmid R483 mediates plasmid stabilization by killing of plasmid-free cells. The pnd mRNA is very stable and can be translated into PndA protein, a cell toxin which kills the cells from within by damaging the cell membrane. Translation of the pnd mRNA is inhibited by the PndB antisense, a small labile RNA of 63 nt. The rapid decay of the PndB antidote leads to onset of PndA synthesis in plasmid-free segregants or after addition of rifampicin. Surprisingly however, the full-length pnd mRNA was found to be translationally inactive whereas a 3'-end truncated version of it was found to be active. We have therefore suggested previously, that the 3'-end of the full-length pnd mRNA encodes a fold-back inhibitory sequence (fbi), which prevents its translation. Here we present an analysis of the metabolism of the pnd mRNAs. A mutational analysis shows that single point mutations in the fbi motif results in more rapid truncation. The fbi mutations could not be complemented by second-site mutations in either of the pndA or pndC Shine-Dalgarno (SD) elements. Surprisingly, mutations in the pndC SD element also lead to a more rapid truncation. The effect of these latter mutations was, however, complemented by mutations in a proposed anti-SD element upstream of the pndC SD. Mutations in the anti-SD element were lethal. These results show, that the pnd mRNA contains two negative control elements, one located in its very 3'-end (fbi), and one located just upstream of the pndC SD region (the anti-SD element). These observations add to the complexity of the induction scheme previously proposed to explain activation of pndA expression in plasmid-free cells: In addition to its negative effect of translation, the fbi structure also maintains a reduced processing rate in the 3' end of the mRNA. This permits the accumulation of a reservoir of pnd mRNA, which can be activated by 3'-end processing in plasmid-free cells. The anti-SD may prevent translation of the pnd mRNA during transcription, thus preventing detrimental synthesis of toxin. PMID- 7783192 TI - A transcriptional role for conserved footprinting sequences within the larval promoter of a Drosophila alcohol dehydrogenase gene. AB - All Drosophila alcohol dehydrogenase (Adh) genes that are expressed in larvae display strong transcription in the larval fat body. To identify and characterize elements needed for Adh promoter function, footprinting analysis of the Drosophila affinidisjuncta Adh gene was performed with stage-specific nuclear proteins from embryos and larvae. Multiple sites upstream of the larval promoter were protected from deoxyribonuclease digestion by both embryonic and larval extracts. Comparison with foot-printing results for Adh genes from other Drosophila species revealed only one nuclease-protected region that is conserved in both sequence and position. Clustered point mutations in this sequence were analyzed by footprinting analysis, transient transformation and in vitro transcription. Two separate sequences in this footprinting region exerted positive effects on transcription from the Adh proximal promoter in the larval fat body. The effects of these sequences on gene expression were synergistic. One of these sequences, TGATAA, bound in vitro to Drosophila melanogaster box A binding factor protein, as shown by gel mobility shift assays. This is the first direct demonstration of specific protein-DNA interactions influencing transcription of a Drosophila Adh gene in the larval fat body. PMID- 7783194 TI - A complete plasmid-based complementation system for RNA coliphage Q beta: three proteins of bacteriophages Q beta (group III) and SP (group IV) can be interchanged. AB - Our laboratory has established a bacteriophage Q beta cDNA-containing plasmid system in which virtually all coding defects present within the 4217 nucleotide Q beta genome can be complemented in trans. In this system, Q beta minus strand RNAs are constitutively transcribed from plasmid cDNA by Escherichia coli RNA polymerase. Replication of these minus strands results in the synthesis of Q beta plus RNA, thereby triggering an infectious cycle in which Q beta phase particles are generated. Genetically engineered Q beta genome mutations that result in defective viral proteins can be complemented in trans by the products of one or more Q beta helper plasmids that express either: (1) Q beta maturation protein, which can complement defects in the Q beta maturation cistron (nucleotides 61 to 1320); (2) Q beta readthrough protein, which can complement defects in the readthrough cistron (nucleotides 1344 to 2330); or (3) Q beta replicase, which can complement defects in the replicase cistron (nucleotides 2352 to 4118). Each plasmid component of this system contains a unique origin of replication and carries a different antibiotic gene, thereby enabling all combinations of these plasmids to coexist in the same host. We have further developed a second series of helper plasmids that generate the corresponding viral proteins of the related group IV RNA phage SP. Each of these SP helper proteins can complement respective defects within the Q beta genome with efficiencies similar to those observed for the Q beta helper proteins. It is now possible to supply functional Q beta or SP proteins in trans to examine Q beta genomes that contain protein coding defects for their ability to synthesize Q beta proteins, replicate Q beta RNA, assemble virions, and/or lyse the host cell. PMID- 7783195 TI - Multiple interacting elements delineate an ecdysone-dependent regulatory region with secondary responsive character. AB - Within the 2.2 kb region between hsp23 and gene 1 of the small heat shock gene locus 67B1 of Drosophila melanogaster, an approximately 1 kb perturbation of the chromatin architecture has previously been observed to occur in response to the steroid hormone ecdysone. Transient expression assays in hormonally-responsive Drosophila tissue culture cells utilizing hsp70-lacZ chimeric reporter constructs revealed the presence of ecdysone-dependent regulatory sequences in this hsp23 gene 1 intergenic region. The analysis delimited five functional segments: three core regions which were completely encompassed within the region of chromatin perturbation, and two gene-proximal regions which appear to be functionally equivalent under some circumstances. None of the delineated regions was capable of stimulating expression independently, while sub-maximal expression was obtained when combinations of two or three regions were monitored. This requirement for multiple DNA segments to drive maximal transcription suggested that cooperative interactions between the regions were essential for full hormonal responsiveness. Unexpectedly, no binding of the ecdysone receptor was detectable within any of the delineated regions, implying the involvement of multiple non-receptor factors in the observed hormonal responsiveness. The ecdysone-dependent activation of reporter constructs driven by these sequences showed a significant time lag and was coupled with a marked sensitivity to low concentrations of cycloheximide. The data obtained strongly suggest that the cis acting elements delimited within the hsp23-gene 1 intergenic region respond to ecdysone in a secondary manner, presumably by requiring interaction with the product(s) of primary ecdysone-responsive genes. PMID- 7783196 TI - Stabilization of a ribosomal RNA tertiary structure by ribosomal protein L11. AB - Interactions between ribosomal protein L11 and a domain of large subunit rRNA have been highly conserved and are essential for efficient protein synthesis. To study the effects of L11 on rRNA folding, a homolog of the Escherichia coli L11 gene has been amplified from Bacillus stearothermophilus DNA and cloned into a phage T7 polymerase-based expression system. The expressed protein is 93% homologous to the L11 homolog from Bacillus subtilis, denatures at temperatures above 72 degrees C, and has nearly identical rRNA binding properties as the Escherichia coli L11 in terms of RNA affinity constants and their dependences on temperature, Mg2+ concentration, monovalent cation, and RNA mutations. Mg2+ and NH4+ are specifically bound by the RNA-protein complex, with apparent ion-RNA affinities of 1.6 mM-1 and 19 M-1, respectively, at 0 degree C. The effect of the thermostable L11 on the unfolding of a 60 nucleotide rRNA fragment containing its binding domain has been examined in melting experiments. The lowest temperature RNA transition, which is attributed to tertiary structure unfolding, is stabilized by approximately 25 degrees C, and the interaction has an intrinsic enthalpy of approximately 13 kcal/mol. The thermal stability of the protein-RNA complex is enhanced by increasing Mg2+ concentration and by NH4+ relative to Na+. Thus L11, NH4+, and Mg2+ all bind and stabilize the same rRNA tertiary interactions, which are conserved and presumably important for ribosome function. PMID- 7783197 TI - Mutual stabilisation of bacteriophage Mu repressor and histone-like proteins in a nucleoprotein structure. AB - Integration host factor (IHF) binds in a sequence-specific manner to the bacteriophage Mu early operator. It participates with bound Mu repressor, c, in building stable, large molecular mass nucleoprotein complexes in vitro and enhances repression of early transcription in vivo. We demonstrate that, when the specific IHF binding site with the operator is mutated, the appearance of large molecular mass complexes still depends on IHF and c, but the efficiency of their formation is reduced. Moreover, the IHF-like HU protein, which binds DNA in a non sequence-specific way, can substitute for IHF and participate in complex formation. Since the complexes require both c and a host factor (IHF or HU), the results imply that these proteins stabilise each other within the nucleoprotein structures. These results suggest that IHF and HU are directed to the repressor operator complexes, even in the absence of detectable sequence-specific binding. This could be a consequence of their preferential recognition of DNA containing a distortion such as that introduced by repressor binding to the operator. The histone-like proteins could then stabilise the nucleoprotein complexes simply by their capacity to maintain a bend in DNA rather than by specific protein-protein interactions with c. This model is supported by the observation that the unrelated eukaryotic HMG-1 protein, which exhibits a similar marked preference for structurally deformed DNA, is also able to participate in the formation of higher-order complexes with c and the operator DNA. PMID- 7783198 TI - Identification and analysis of multigene families by comparison of exon fingerprints. AB - Gene families are often recognised by sequence homology using similarity searching to find relationships, however, genomic sequence data provides gene architectural information not used by conventional search methods. In particular, intron positions and phases are expected to be relatively conserved features, because mis-splicing and reading frame shifts should be selected against. A fast search technique capable of detecting possible weak sequence homologies apparent at the intron/exon level of gene organization is presented for comparing spliceosomal genes and gene fragments. FINEX compares strings of exons delimited by intron/exon boundary positions and intron phases (exon fingerprint) using a global dynamic programming algorithm with a combined intron phase identity and exon size dissimilarity score. Exon fingerprints are typically two orders of magnitude smaller than their nucleic acid sequence counterparts giving rise to fast search times: a ranked search against a library of 6755 fingerprints for a typical three exon fingerprint completes in under 30 seconds on an ordinary workstation, while a worst case largest fingerprint of 52 exons completes in just over one minute. The short "sequence" length of exon fingerprints in comparisons is compensated for by the large exon alphabet compounded of intron phase types and a wide range of exon sizes, the latter contributing the most information to alignments. FINEX performs better in some searches than conventional methods, finding matches with similar exon organization, but low sequence homology. A search using a human serum albumin finds all members of the multigene family in the FINEX database at the top of the search ranking, despite very low amino acid percentage identities between family members. The method should complement conventional sequence searching and alignment techniques, offering a means of identifying otherwise hard to detect homologies where genomic data are available. PMID- 7783199 TI - Crystal structure of a pyrimidine dimer-specific excision repair enzyme from bacteriophage T4: refinement at 1.45 A and X-ray analysis of the three active site mutants. AB - Crystallographic study of bacteriophage T4 endonuclease V, which is involved in the initial step of the pyrimidine dimer-specific excision repair pathway, has been carried out with respect to the wild-type and three different mutant enzymes. This enzyme catalyzes the cleavage of the N-glycosyl bond at the 5'-side of the pyrimidine dimer, and subsequently incises the phosphodiester bond at the apyrimidinic site through a beta-elimination reaction. The structure of the wild type enzyme refined at 1.45 A resolution reveals the detailed molecular architecture. The enzyme is composed of a single compact domain classified as an all-alpha structure. The molecule is stabilized mainly by three hydrophobic cores, two of which include many aromatic side-chain interactions. The structure has a unique folding motif, where the amino-terminal segment penetrates between two major alpha-helices and prevents their direct contact, and it is incompatible with the close-packing category of helices for protein folding. The concave surface, covered with many positive charges, implies an interface for DNA binding. The glycosylase catalytic center, which comprises Glu23 and the surrounding basic residues Arg3, Arg22 and Arg26, lie in this basic surface. The crystal structures of the three active-site mutants, in which Glu23 was replaced by Gln(E23Q) and Asp (E23D), respectively, and Arg3 by Gln (R3Q), have been determined at atomic resolution. The backbone structures of the E23Q and R3Q mutants were almost identical with that of the wild-type, while the E23D mutation induces a small, but significant, change in the backbone structure, such as an increase of the central kink of the H1 helix at Pro25. In the catalytic center of the glycosylase, however, these three mutations do not generate notable movements of protein atoms, except for significant shifts of some bound water molecules. Thus, the structural differences between the wild-type and each mutant are confined to the remarkably small region around their replaced chemical groups. Combined with the biochemical studies and the difference circular dichroism measurements, these results allow us to conclude that the negatively charged carboxyl group of Glu23 is essential for the cleavage of the N-glycosyl bond, and that the positively charged guanidino group of Arg3 is crucial to bind the substrate, a DNA duplex containing a pyrimidine dimer. The amino terminal alpha amino group is located at a position approximately 4.4 A away from the carboxyl group of Glu23. These structural features are generally consistent with the reaction scheme proposed by Dodson and co-workers. PMID- 7783200 TI - A molecular model for the redox potential difference between thioredoxin and DsbA, based on electrostatics calculations. AB - The disulphide active sites of thioredoxin and DsbA are known to possess a high degree of structural homology. However, DsbA is a much stronger oxidant than thioredoxin. The redox potential difference between DsbA and thioredoxin has been measured to be 160 mV, equivalent to a shift of 15.4 kJ/mol in the reduced/oxidised equilibrium. Electrostatics calculations have been used to study the relative stabilities of the reduced forms of the two proteins. Model calculations suggest that much of the redox potential difference between DsbA and thioredoxin arises form altered stabilisation of the exposed and ionised thiolates of the reduced forms, supporting suggestions previously made on the basis of experimental studies. The calculations have been used to construct a molecular model for the difference in thiolate stabilisation. Although specific interactions, such as thiolate-NH 35 (thioredoxin)/33 (DsbA), provide substantial stabilisation in each reduced protein, the difference between thioredoxin and DsbA is predicted to reside in several side-chain and main-chain groups acting in concert. Residues H32 and Q97 in DsbA are predicted to contribute, along with substantial regions of the polypeptide backbone in the protein domain which is common to DsbA and thioredoxin. Increased thiolate stabilisation by the peptide dipoles is suggested to arise from altered main-chain disposition, and the effect of the additional protein domain of DsbA on the electric field. Peptide dipoles in a region of about 20 residues close to the active site disulphide are predicted to contribute significantly to the redox potential difference. PMID- 7783201 TI - Crystallisation of RNA-protein complexes. II. The application of protein engineering for crystallisation of the U1A protein-RNA complex. AB - The hairpin is one of the most commonly found structural motifs of RNA and is often a binding site for proteins. Crystallisation of U1A spliceosomal protein bound to a RNA hairpin, its natural binding site on U1snRNA, is described. RNA oligonucleotides were synthesised either chemically or by in vitro transcription using T7 RNA polymerase and purified to homogeneity by gel electrophoresis. Crystallisation trials with the wild-type protein sequence and RNA hairpins containing various stem sequences and overhanging nucleotides only resulted in a cubic crystal form which diffracted to 7-8 A resolution. A new crystal form was grown by using a protein variant containing mutations of two surface residues. The N-terminal sequence of the protein was also varied to reduce heterogeneity which was detected by protein mass spectrometry. A further crystallisation search using the double mutant protein and varying the RNA hairpins resulted in crystals diffracting to beyond 1.7 A. The methods and strategy described in this paper may be applicable to crystallisation of other RNA-protein complexes. PMID- 7783202 TI - Isolation, crystallization, crystal structure analysis and refinement of allophycocyanin from the cyanobacterium Spirulina platensis at 2.3 A resolution. AB - The phycobiliprotein allophycocyanin from the cyanobacterium Spirulina platensis has been isolated and crystallized. The crystals belong to space group P6(3)22 with cell constants a = b = 101.9 A, c = 130.6 A, alpha = beta = 90 degrees, gamma = 120 degrees, with one (alpha beta) monomer in the asymmetric unit. The three-dimensional structure of the (alpha beta) monomer was solved by multiple isomorphous replacement. The crystal structure has been refined in a cyclic manner by energy-restrained crystallographic refinement and model building. The conventional crystallographic R-factor of the final model is 19.6% with data from 8.0 to 2.3 A. The molecular structure of the subunits resembles other solved phycobiliprotein structures. In comparison to C-phycocyanin and b-phycoerythrin the major differences arise from deletions and insertions of segments involved in the protein-chromophore interactions. The stereochemistry of the alpha 84 and beta 84 chiral atoms are C(2)-R, C(3)-R and C(31)-R. The configuration (C(4)-Z, C(10)-Z and C(15)-Z) and the conformation (C(5)-anti, C(9)-syn and C(14)-anti) are equal for both chromophores. PMID- 7783203 TI - Determination of the solution structure of Apo calbindin D9k by NMR spectroscopy. AB - The three-dimensional structure of apo calbindin D9k has been determined using constraints generated from nuclear magnetic resonance spectroscopy. The family of solution structures was calculated using a combination of distance geometry, restrained molecular dynamics, and hybrid relaxation matrix analysis of the nuclear Overhauser effect (NOE) cross-peak intensities. Errors and inconsistencies in the input constraints were identified using complete relaxation matrix analyses based on the results of preliminary structure calculations. The final input data consisted of 994 NOE distance constraints and 122 dihedral constraints, aided by the stereospecific assignment of the resonances from 21 beta-methylene groups and seven isopropyl groups of leucine and valine residues. The resulting family of 33 structures contain no violation of the distance constraints greater than 0.17 A or of the dihedral angle constraints greater than 10 degrees. The structures consist of a well-defined, antiparallel four-helix bundle, with a short anti-parallel beta-interaction between the two unoccupied calcium-binding loops. The root-mean-square deviation from the mean structure of the backbone heavy-atoms for the well-defined helical residues is 0.55 A. The remainder of the ion-binding loops, the linker loop connecting the two sub-domains of the protein, and the N and C termini exhibit considerable disorder between different structures in the ensemble. A comparison with the structure of the (Ca2+)2 state indicates that the largest changes associated with ion-binding occur in the middle of helix IV and in the packing of helix III onto the remainder of the protein. The change in conformation of these helices is associated with a subtle reorganization of many residues in the hydrophobic core, including some side-chains that are up to 15 A from the ion binding site. PMID- 7783204 TI - Slow ligand-induced transitions in the allosteric phosphofructokinase from Escherichia coli. AB - The fluorescence of the unique tryptophan residue of the allosteric phosphofructokinase from Escherichia coli varies upon binding of any ligand, whether substrate or effector, suggesting that the protein undergoes a conformational change. This fluorescent probe has been exploited to determine the rates of the structural transitions that occur upon ligand binding and that are responsible for the remarkable allosteric behavior of this enzyme. The kinetics of fluorescence changes measured after rapidly mixing phosphofructokinase with one of its ligands show the presence of several allosteric transitions with widely different rates, ranging from a few hundred s-1 to less than 0.1 s-1. The rate of each conformational change increases with the concentration of the ligand used to trigger it, suggesting that ligands induce a conformational change and do not displace a pre-existing equilibrium. The hypothesis that each ligand stabilizes a different conformational state of the protein is confirmed by the kinetics of displacement of one ligand by another: for instance, the binary complexes between phosphofructokinase and either its substrate, fructose-6 phosphate, or its allosteric activator, ADP, have the same low fluorescence and should be in the same active state, but they show different rates of conformational transition upon binding the inhibitor phosphoenolpyruvate. It appears that phosphofructokinase can exist in more than two states. Some conformational changes between these multiple states are slow enough to play an important role in the kinetics of the reaction catalyzed by phosphofructokinase, and could even explain part of its allosteric behavior. These results show that steady-state measurements are not sufficient to analyze the regulatory properties of E. coli phosphofructokinase. PMID- 7783205 TI - The complexity and accuracy of discrete state models of protein structure. AB - The prediction of protein structure depends on the quality of the models used. In this paper, we examine the relationship between the complexity and accuracy of representation of various models of protein alpha-carbon backbone structure. First, we develop an efficient algorithm for the near optimal fitting of arbitrary lattice and off-lattice models of polypeptide chains to their true X ray structures. Using this, we show that the relationship between the complexity of a model, taken as the number of possible conformational states per residue, and the simplest measure of accuracy, the root-mean-square deviation from the X ray structure, is approximately (Accuracy) varies; is directly proportional to (Complexity)-1/2. This relationship is insensitive to the particularities of individual models, i.e. lattice and off-lattice models of the same complexity tend to have similar average root-mean-square deviations, and this also implies that improvements in model accuracy with increasing complexity are very small. However, other measures of model accuracy, such as the preservation of X-ray residue-residue contacts and the alpha-helix, do distinguish among models. In addition, we show that low complexity models, which take into account the uneven distribution of residue conformations in real proteins, can represent X-ray structures as accurately as more complex models, which do not: a selected 6-state model can represent protein structures almost as accurately (1.7 A root-mean square) as a 17-state lattice model (1.6 A root-mean-square). Finally, we use a novel optimization procedure to generate eight 4-state models, which fit native proteins to an average of 2.4 A, and preserve 85% of native residue-residue contacts. We discuss the implications of these findings for protein folding and the prediction of protein conformation. PMID- 7783206 TI - A supprescin from a phytopathogenic fungus deactivates transcription of a plant defense gene encoding phenylalanine ammonia-lyase. AB - Both elicitor and supprescin (suppressor) are present in the pycnospore germination fluid of a pea pathogen Mycospharella pinodes. A nuclear run-on assay revealed that supprescin rapidly deactivated elicitor-triggered transcription of the gene encoding phenylalnine ammonia-lyase in pea epicotyl tissues. The mechanism underlying the deactivation of the plant defense gene by signal molecules secreted from the fungal pathogen was investigated. Cis-acting sequences and trans-acting factors responsive to supprescin in a TATA-proximal region of a member of the phenylalanine ammonia-lyase gene family in pea were examined in vitro. Gel mobility-shift assays and DNase I footprinting analysis revealed that the promoter region of PSPAL2 was modified by the binding of nuclear factors at multiple sites that were possibly involved in supprescin mediated deactivation. The prominent changes by supprescin were observed at boxes 2 and 4 and near exonic sequences. PMID- 7783207 TI - The DNA sequence of equine herpesvirus 2. AB - The complete DNA sequence of equine herpesvirus 2 (EHV-2) strain 86/67 was determined. The genome is 184,427 bp in size and has a base composition of 57.5% G + C. Unusually for a herpesvirus, about a third of the sequence distributed in several large blocks appears not to encode proteins. The 79 open reading frames that were identified as probably polypeptide-coding are predicted to encode 77 distinct proteins. Amino acid sequence comparisons confirmed that EHV-2 is a gamma-herpesvirus that is genetically collinear with herpesvirus saimiri (HVS; a gamma 2-herpesvirus) and Epstein-Barr virus (EBV; a gamma 1-herpesvirus), with a closer relationship to the former. Moreover, EHV-2 specifies eight proteins that have counterparts in HVS but not in EBV and only a single protein that has a homologue in EBV but not in HVS (EBV BCRF1, which encodes an interleukin 10-like protein). EHV-2 also encodes three potential G protein-coupled receptors, one with a counterpart in HVS that is specific for alpha chemokines, another with a counterpart in human cytomegalovirus (a beta-herpesvirus), which is specific for beta chemokines, and a third that is assigned more tentatively and lacks detectable counterparts in other herpesviruses. PMID- 7783208 TI - Cold denaturation of CheY. AB - The thermal stability of the bacterial chemotaxis protein CheY from Salmonella typhimurium has been examined by thermal denaturation at pH 7.0 in the presence of guanidine-HCl and urea. For both denaturants, thermal denaturation monitored by circular dichroism spectropolarimetry consists of transitions both above and below 25 degrees C, which is strong evidence for a heat capacity change that is > or = 1500 cal/(mol K) upon unfolding. While many data for chemical and thermal denaturation are consistent with data for CheY from Escherichia coli, the observation of cold denaturation for S. typhimurium CheY is inconsistent with the small heat capacity change, 600 to 850 cal/(mol K), reported for denaturation of the E. coli protein. PMID- 7783209 TI - The KIN28 gene is required both for RNA polymerase II mediated transcription and phosphorylation of the Rpb1p CTD. AB - Kin28p, associated with cyclin Ccl1p, is a putative cyclin-dependent kinase (CDK) of the p34cdc2 family in Saccharomyces cerevisiae. Search for mutations co-lethal (syn mutations) with a kin28 thermosensitive mutation (kin28-ts3) has uncovered genetic interactions between gene KIN28 and genes RAD3, SIN4, STI1 and CDC37. The genetic interaction between KIN28 and the CDC37 cell division cycle gene suggests that a connection exists between the activity of CDK-Kin28p and cell-cycle progression. Both RAD3 and SIN4 gene products are implicated in the RNA polymerase II transcription process. Here we show that RNA polymerase II transcription is drastically reduced in a kin28-ts mutant, at restrictive temperature. This impairment correlates with a markedly decreased phosphorylation of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Rpb1p). Thus, the Kin28 gene product is required in vivo for RNA polymerase II phosphorylation and transcriptional activity as recently suggested by experiments using an in vitro reconstituted system. PMID- 7783210 TI - RNA binding, packaging and polymerase activities of the different incomplete polymerase complex particles of dsRNA bacteriophage phi 6. AB - phi 6 is an enveloped dsRNA bacterial virus. Its segmented genome resides inside the virion associated polymerase complex which is formed by four proteins (P1, P2, P4 and P7) encoded by the viral L segment. Complete and incomplete polymerase complex particles can be produced using cDNA copies of this largest genome segment. We have analysed the capacity of the different purified particles to (1) package phi 6 (+) sense genomic precursors and unspecific RNA, (2) synthesize (-) and (+) strands and (3) bind phi 6 specific and unspecific RNAs. Both (-) and (+) strand synthesis polymerase activities were found to be associated with protein P2. In addition to complete particles, particles lacking protein P2 were found to package and protect genomic precursor ssRNAs. Protein P7 was needed for efficient packaging. Regulation and specificity of the packaging were found to be independent of P2. Particles composed of proteins P1 and P4 did not package or protect RNA but did bind phi 6 genomic (+) strand RNAs. The three phi 6 (+) strands bound in equal amounts to the particles when tested alone in a filter binding assay. In competition experiments they competed each other for binding, indicating that individual binding sites for the three genomic (+) strands do not exist. Differences in RNA binding competition among the four particles were observed, suggesting that packaging specificity is achieved by complex interactions of proteins and genomic (+) strand RNAs during the advancement of the packaging process after the initial binding events. PMID- 7783211 TI - A reporter gene to analyse the hypermutation of immunoglobulin genes. AB - The affinity maturation of antibodies is driven by somatic hypermutation which is localized to specific segments of the coding genes. The information available on this process derives from studies in vivo. With the intention of developing new approaches, we have constructed a fusion gene between a kappa chain and a selectable neomycin resistance gene, neor. The neor gene, which includes the SV40 small t intron and polyadenylation site, but not the upstream elements nor its first 12 amino acids, is an in-frame substitution of the FR2-CDR3 fragment of a rearranged V kappa OX1-J kappa 5 gene. Expression of neor activity is therefore dependent on the upstream immunoglobulin sequence. A stop codon was placed in the CDR1 region so that only mutants survive treatment with geneticin sulphate (G418). The effectiveness of the system was tested by transfecting the NS0 myeloma cell line and isolating spontaneous mutants. Neomycin-resistant clones arose at an estimated rate of 1 x 10(-8)/cell division, and over 90% were authentic structural mutants. Unlike the somatic hypermutations, the majority arose by in-frame deletions including the stop codon, although up to 30% involved a point mutation. The reporter gene was then modified by substituting all the sequences downstream of the J kappa 5 with others known to be required for full hypermutation in vivo. Different cell lines were transfected and G418-resistant clones analyzed. No significant increase in the rate of reversion or in the generation of point mutations versus deletions was detected, even using conditioned culture medium. In the presence of azacytidine however, a mutant involving multiple events (single base addition and deletion plus two point mutations) was detected. The reporter gene system therefore seems suitable to test culture conditions and modifications of the host cells aimed at the derivation of an in vitro assay of somatic hypermutation. PMID- 7783212 TI - E-box variants direct formation of distinct complexes with the basic helix-loop helix protein ALF1. AB - The murine transcription factor ALF1 belongs to the class of basic helix-loop helix proteins specific for the NCAGNTGN-version of the E-box. Binding of homodimeric ALF1 to variants of this motif was studied by a combination of binding site selection technology and DNA modification interference analysis. The results showed that substitutions at the non-conserved positions in the E-box sequence could cause profound alterations in the patterns of specific contacts at the protein-DNA interface. Thus, both the overall extent of the binding region and the backbone phosphate contact pattern differed markedly between closely related E-boxes with similar affinities for ALF1. The identity of the base at the inner N was an important determinant of contact pattern specification. The E-box variants differed in their ability to mediate ALF1 dependent transcriptional activation in vivo. We discuss the possibility that adaptability in basic helix loop-helix protein-DNA interactions can result in complexes with different functional properties. PMID- 7783213 TI - Structures of fd gene 5 protein.nucleic acid complexes: a combined solution scattering and electron microscopy study. AB - Small-angle scattering and electron microscopy studies of fd gene 5 protein (g5p) and reconstituted g5p.nucleic acid complexes have been used to test models for the complexes and evaluate their uniqueness. In addition, we have obtained new information on the dependence of nucleotide type and protein/nucleotide (P/N) ratio on the structure of the complexes. Reconstituted complexes were made with single-stranded fd viral DNA (fd ssDNA), poly[d(A)] and poly[r(A)]. All complexes form similar left-handed, flexible superhelices having approximately the same diameter, but the pitch differs among these complexes. The g5p protein is a dimer in solution and the dimers associate to form a superhelical framework to which the polynucleotide is attached. The combined X-ray and neutron scattering data confirm the nucleic acid is inside the protein superhelix. A Monte Carlo integration modeling procedure applied to the scattering data was used to systematically test large numbers of possible models for each complex, and previously proposed models based on parameters obtained from electron microscopy were found to be essentially correct and unique. The data on the complexes with different P/N ratios showed that mass per unit length values decreased while the rise per dimer and pitch of the superhelix increased for g5p.fd-ssDNA complexes with decreasing P/N ratios. PMID- 7783214 TI - NMR cross-relaxation investigated by molecular dynamics simulation: a case study of ubiquitin in solution. AB - A one nanosecond molecular dynamics simulation of ubiquitin in solution has been used for the calculation of the total dipolar, the radial and the reorientational correlation functions of 174 interproton NOEs and the 76 peptide chain NH vectors. The NOEs have been classified according to the structural elements they are associated with. Using multiexponential fits of the raw data spectral densities and cross-relaxation rate constants have been determined. Statistical distributions of correlation function parameters are given. On the basis of these data the assumptions underlying the standard method for distance measurement using NOE enhancements have been scrutinized. The separability of elongation and reorientation is verified for the vast majority of NOEs, but the rigid-body assumption is not supported by the simulation results. Relying on a spectral density expression that neither makes use of the product approximation nor neglects spatially restricted motion, a "bias-free" (with regard to molecular motion) distance measurement method is suggested and compared with the standard method. Errors in distances up to 24% and 50% occur due to the neglect of the dispersion of order parameters and correlation times, respectively. The preconditions for a class-specific calibration method have been investigated. Within the framework of the product approximation a method for decomposing the total cross-relaxation rate constant into contributions from radial and angular motion has been developed and applied. In several cases distance fluctuation contributes significantly to cross-relaxation with both amplitude and time behaviour. PMID- 7783215 TI - A thermodynamic study of mutant forms of Streptomyces subtilisin inhibitor. I. Hydrophobic replacements at the position of Met103. AB - The thermodynamic effects of replacing the Met residue at amino acid position 103 of Streptomyces subtilisin inhibitor with other non-polar aliphatic residues were studied by means of differential scanning calorimetry. All but the Leu mutant, which is as stable as the wild-type but has different cooperative units in the course of unfolding, showed destabilization in terms of free energy. Similar losses in free energy, however, were caused by different reasons, i.e. by increased entropy for the Ala mutant and by decreased enthalpy for the Ile mutant, with a tendency that increases in entropy are accompanied by increases in enthalpy. The gain in entropy that caused the largest loss in free energy for the Gly mutant was unexpectedly smaller than that for the Ala mutant. The changes in enthalpy and entropy induced by the mutations exhibited some correlations with hydrophobicity, while no clear correlation was found between the changes in free energy and hydrophobicity. PMID- 7783216 TI - A thermodynamic study of mutant forms of Streptomyces subtilisin inhibitor. II. Replacements at the interface of dimer formation, Val13. AB - Amino acid replacements in a homodimeric protein, Streptomyces subtilisin inhibitor, at the position of Val13, which is located at the center of the beta sheet interface of the domain-domain interaction, changed both the overall stability and the denaturational scheme. All the mutant forms lost stability, losses in free energy at 82.21 degrees C at pH 7.0 obtained by calorimetric measurements ranging from 10.3 kcal (mol dimer)-1 for the Gly mutant, which involved a loss in enthalpy without a compensating loss in entropy, to 0.84 kcal (mol dimer)-1 for the Ile mutant, which involved comparable losses in enthalpy and entropy. A gain in enthalpy for the Ala mutant was overcome by a gain in entropy, resulting in a loss in free energy by 6.78 kcal (mol dimer)-1. It was found that decreases in enthalpy and entropy showed good correlation with increasing side-chain hydrophobicity, while no such correlation was present for free energy. Replacements with Gly, Ala, Met and Phe altered the thermal denaturational scheme from N2 reversible 2D, which was the case for the Leu and Ile mutants as well as for the wild-type, to N2 reversible 2N* reversible 2D, where the first step can be regarded as a dissociation of the native dimer followed by a major unfolding in the second step. The free energy acquired by forming the dimer was estimated to be 2.03 kcal mol-1 for the Ala mutant at 66.95 degrees C at pH 9.5 and lower for the other three mutants. PMID- 7783217 TI - A thermodynamic study of mutant forms of Streptomyces subtilisin inhibitor. III. Replacements of a hyper-exposed residue, Met73. AB - Amino acid replacements of Met73, which is hyper-exposed in the native structure, with Asp, Glu, Lys, Gly, Ala, Val, Leu or Ile changed the stability of Streptomyces subtilism inhibitor by +1.60 to -0.94 kcal/mol-1 in free energy at 82.21 degrees C at pH 7.0, with higher hydrophobicity of the replacing amino acid side-chain showing a correlation with lower stability. Thermodynamic parameters obtained from detailed calorimetric analyses gave a nearly proportional relation between the entropy change and the enthalpy change of denaturation, i.e. T delta delta S degrees = -0.03 (+/- 0.11) + 1.14 (+/- 0.03) delta delta H, with the linear correlation coefficient 0.996 for 18 data points. This proportionality observed uniquely for the substitutions at position 73 was caused primarily by the water/side-chain interaction, or hydration effect, which can account for the majority of the changes in enthalpy and entropy induced by the mutations. PMID- 7783218 TI - Investigating the structural determinants of the p21-like triphosphate and Mg2+ binding site. AB - Amongst the superfamily of nucleotide binding proteins, the classical mononucleotide binding fold (CMBF), is the one that has been best characterized structurally. The common denominator of all the members is the triphosphate/Mg2+ binding site, whose signature has been recognized as two structurally conserved stretches of residues: the Kinase 1 and 2 motifs that participate in triphosphate and Mg2+ binding, respectively. The Kinase 1 motif is borne by a loop (the P loop), whose structure is conserved throughout the whole CMBF family. The low sequence similarity between the different members raises questions about which interactions are responsible for the active structure of the P-loop. What are the minimal requirements for the active structure of the P-loop? Why is the P-loop structure conserved despite the diverse environments in which it is found? To address this question, we have engineered the Kinase 1 and 2 motifs into a protein that has the CMBF and no nucleotide binding activity, the chemotactic protein from Escherichia coli, CheY. The mutant does not exhibit any triphosphate/Mg2+ binding activity. The crystal structure of the mutant reveals that the engineered P-loop is in a different conformation than that found in the CMBF. This demonstrates that the native structure of the P-loop requires external interactions with the rest of the protein. On the basis of an analysis of the conserved tertiary contacts of the P-loop in the mononucleotide binding superfamily, we propose a set of residues that could play an important role in the acquisition of the active structure of the P-loop. PMID- 7783219 TI - The 1.9 A crystal structure of a nucleoside diphosphate kinase complex with adenosine 3',5'-cyclic monophosphate: evidence for competitive inhibition. AB - The X-ray structure of Myxococcus xanthus nucleoside diphosphate (NDP) kinase complexed with adenosine 3',5'-cyclic monophosphate (cAMP) has been determined. The structure was solved by difference Fourier analysis. The refined structure has a crystallographic R-factor of 0.17 at 1.9 A resolution. The phosphoryl group and ribose moiety make extensive polar interactions with the protein, whereas the base interacts only with two hydrophobic residues. The comparison with the structure of the enzyme complex with the substrate adenosine diphosphate (ADP) reported earlier shows that cAMP and ADP interact similarly with the enzyme. The base of the cAMP is present in two conformations, syn and anti, with respect to the sugar. The syn conformer is dominant. Based on the effect of cAMP on phosphorylation of the human NDP kinase NM23, it had been proposed that cAMP might interact with NDP kinase in a manner distinct from other nucleotides. However, the structure of the M. xanthus NDP kinase/cAMP complex indicates that the nucleotide is a competitive inhibitor of the enzyme and occupies the usual nucleotide site. Kinetic assays of the NDP kinase activity in the presence of cAMP were done. Their results are consistent with a competitive character of the cAMP inhibition. PMID- 7783220 TI - Atomic environment energies in proteins defined from statistics of accessible and contact surface areas. AB - Atomic contact potentials are derived by statistical analysis of atomic surface contact areas versus atom type in a database of non-homologous protein structures. The atomic environment is characterized by the surface area accessible to solvent and the surface of contacts with polar and non-polar atoms. Four types of atoms are considered, namely neutral polar atoms from protein backbones and from protein side-chains, non-polar atoms and charged atoms. Potential energies delta Ej(E) are defined from the preference for an atom of type j to be in a given environment E compared to the expected value if everything was random; Boltzmann's law is then used to transform these preferences into energies. These new potentials very clearly discriminate misfolded from correct structural models. The performance of these potentials are critically assessed by monitoring the recognition of the native fold among a large number of alternative structural folding types (the hide-and-seek procedure), as well as by testing if the native sequence can be recovered from a large number of randomly shuffled sequences for a given 3D fold (a procedure similar to the inverse folding problem). We suggest that these potentials reflect the atomic short range non-local interactions in proteins. To characterise atomic solvation alone, similar potentials were derived as a function of the percentage of solvent-accessible area alone. These energies were found to agree reasonably well with the solvation formalism of Eisenberg and McLachlan. PMID- 7783221 TI - The Aminoacyl-tRNA Synthetases and the Evolution of the Genetic Code. Proceedings of a workshop. Berkeley, California, July 17-20, 1994. PMID- 7783222 TI - Divergence of glutamate and glutamine aminoacylation pathways: providing the evolutionary rationale for mischarging. AB - Aminoacyl-tRNA for protein synthesis is produced through the action of a family of enzymes called aminoacyl-tRNA synthetases. A general rule is that there is one aminoacyl-tRNA synthetase for each of the standard 20 amino acids found in all cells. This is not universal, however, as a majority of prokaryotic organisms and eukaryotic organelles lack the enzyme glutaminyl-tRNA synthetase, which is responsible for forming Gln-tRNAGln in eukaryotes and in Gram-negative eubacteria. Instead, in organisms lacking glutaminyl-tRNA synthetase, Gln-tRNAGln is provided by misacylation of tRNAGln with glutamate by glutamyl-tRNA synthetase, followed by the conversion of tRNA-bound glutamate to glutamine by the enzyme Glu-tRNAGln amidotransferase. The fact that two different pathways exist for charging glutamine tRNA indicates that ancestral prokaryotic and eukaryotic organisms evolved different cellular mechanisms for incorporating glutamine into proteins. Here, we explore the basis for diverging pathways for aminoacylation of glutamine tRNA. We propose that stable retention of glutaminyl tRNA synthetase in prokaryotic organisms following a horizontal gene transfer event from eukaryotic organisms (Lamour et al. 1994) was dependent on the evolving pool of glutamate and glutamine tRNAs in the organisms that acquired glutaminyl-tRNA synthetase by this mechanism. This model also addresses several unusual aspects of aminoacylation by glutamyl- and glutaminyl-tRNA synthetases that have been observed. PMID- 7783223 TI - Searching tRNA sequences for relatedness to aminoacyl-tRNA synthetase families. AB - tRNA sequences were analyzed for sequence features correlated with known classes of aminoacyl-tRNA synthetase enzymes. The tRNAs were searched for distinguishing nucleotides anywhere in their sequences. The analyses did not find nucleotides predictive of synthetase class membership. We conclude that such nucleotides never existed in tRNA sequences or that they existed and were lost from many of the tRNA sequences during evolution. PMID- 7783224 TI - Phylogenetic analysis of the aminoacyl-tRNA synthetases. AB - Numerous aminoacyl-tRNA synthetase sequences have been aligned by computer and phylogenetic trees constructed from them for the two classes of these enzymes. Branching orders based on a consensus of these trees have been proposed for the two groups. Although the order of appearance can be rationalized to fit many different scenarios having to do with the genetic code, the invention of a system for translating nucleic acid sequences into polypeptide chains must have predated the existence of these proteins. In the past, a variety of schemes has been proposed for matching amino acids and tRNAs. Most of these have invoked direct recognition of one by the other, whether or not the anticodon was involved. Often ignored is the possibility of a nonprotein (presumably RNA) matchmaker for bringing the two into conjunction. If such had been the case, then the contemporary aminoacyl-tRNA synthetases could have entered the system gradually, each specific type replacing its matchmaking RNA counterpart in turn. A simple displacement scheme of this sort accommodates the existence of two different families of these enzymes, the second being introduced well before the first had undergone sufficient genetic duplications to specify the full gamut of amino acids. Such a scheme is also consistent with similar amino acids often, but not always, being the substrates of enzymes with the most similar amino acid sequences. PMID- 7783225 TI - The class II aminoacyl-tRNA synthetases and their active site: evolutionary conservation of an ATP binding site. AB - Previous sequence analyses have suggested the existence of two distinct classes of aminoacyl-tRNA synthetase. The partition was established on the basis of exclusive sets of sequence motifs (Eriani et al. [1990] Nature 347:203-306). X ray studies have now well defined the structural basis of the two classes: the class I enzymes share with dehydrogenases and kinases the classic nucleotide binding fold called the Rossmann fold, whereas the class II enzymes possess a different fold, not found elsewhere, built around a six-stranded antiparallel beta-sheet. The two classes of synthetases catalyze the same global reaction that is the attachment of an amino acid to the tRNA, but differ as to where on the terminal adenosine of the tRNA the amino acid is placed: class I enzymes act on the 2' hydroxyl whereas the class II enzymes prefer the 3' hydroxyl group. The three-dimensional structure of aspartyl-tRNA synthetase from yeast, a typical class II enzyme, is described here, in relation to its function. The crucial role of the sequence motifs in substrate binding and enzyme structure is high-lighted. Overall these results underline the existence of an intimate evolutionary link between the aminoacyl-tRNA synthetases, despite their actual structural diversity. PMID- 7783226 TI - An operational RNA code for amino acids and variations in critical nucleotide sequences in evolution. AB - An operational RNA code relates specific amino acids to sequences/structures in RNA hairpin helices which reconstruct the seven-base-pair acceptor stems of transfer RNAs. These RNA oligonucleotides are aminoacylated by aminoacyl tRNA synthetases. The specificity and efficiency of aminoacylation are generally determined by three or four nucleotides which are near the site of amino acid attachment. These specificity-determining nucleotides include the so-called "discriminator base" and one or two base pairs within the first four base pairs of the helix. With three examples considered here, nucleotide sequence variations between the eubacterial E. coli tRNA acceptor stems and their human cytoplasmic and mitochondrial counterparts are shown to include changes of some of the nucleotides known to be essential for aminoacylation by the cognate E. coli enzymes. If the general locations of the specificity-determining nucleotides are the same in E. coli and human RNAs, these RNA sequence variations imply a similar covariation in sequences/structures of the E. coli and human tRNA synthetases. These covariations would reflect the integral relationship between the operational RNA code and the design and evolution of tRNA synthetases. PMID- 7783227 TI - A comparison of mitochondrial tRNAs in five vertebrates. AB - Sequences of several vertebrate mitochondrial tRNAs were aligned and compared. The comparisons were made in pairs of the tRNAs for an identical amino acid. There are 22 genes for different tRNAs in each vertebrate mitochondrial DNA. The closet similarities were between rat and mouse, the next were between mammals, and the widest difference was between human or rat and Xenopus laevis. However, there were very wide variations between different amino acids in each set of comparisons. The time lapse for each percent of difference greatly increased with evolutionary separation. Most of the nucleotide substitutions appeared to be neutral in character. PMID- 7783228 TI - Speculations on the origin of the genetic code. AB - The most primitive code is assumed to be a GC code: GG coding for glycine, CC coding for proline, GC coding for alanine, CG coding for "arginine." The genetic code is assumed to have originated with the coupling of glycine to its anticodon CC mediated by a copper-montmorillonite. The polymerization of polyproline followed when it was coupled to its anticodon GG. In this case the aminoacyl-tRNA synthetase was a copper-montmorillonite. The first membrane is considered to be a beta sheet formed from polyglycine. As the code grew more complicated, the alternative hydrophobic-hydrophilic polypeptide (alanine-"arginine") was coded for by the alternating CG copolymer. This alternating polypeptide (ala-"arg") began to function as both a primitive membrane and as an aminoacyl-tRNA synthetase. The evolution of protein structure is tightly coupled to the evolution of the membrane. The alpha helix was evolved as lipids became part of the structure of biological membranes. The membrane finally became the fluid mosaic structure that is now universal. PMID- 7783229 TI - Evolution of the aminoacyl-tRNA synthetases and the origin of the genetic code. AB - The aminoacyl-tRNA synthetases exist as two enzyme families which were apparently generated by divergent evolution from two primordial synthetases. The two classes of enzymes exhibit intriguing familial relationships, in that they are distributed nonrandomly within the codon-amino acid matrix of the genetic code. For example, all XCX codons code for amino acids handled by class II synthetases, and all but one of the XUX codons code for amino acids handled by class I synthetases. One interpretation of these patterns is that the synthetases coevolved with the genetic code. The more likely explanation, however, is that the synthetases evolved in the context of an already-established genetic code--a code which developed earlier in an RNA world. The rules which governed the development of the genetic code, and led to certain patterns in the coding catalog between codons and amino acids, would also have governed the subsequent evolution of the synthetases in the context of a fixed code, leading to patterns in synthetase distribution such as those observed. These rules are (1) conservative evolution of amino acid and adapter binding sites and (2) minimization of the disruptive effects on protein structure caused by codon meaning changes. PMID- 7783230 TI - A sensitive and reliable locomotor rating scale for open field testing in rats. AB - Behavioral assessment after spinal cord contusion has long focused on open field locomotion using modifications of a rating scale developed by Tarlov and Klinger (1954). However, on-going modifications by several groups have made interlaboratory comparison of locomotor outcome measures difficult. The purpose of the present study was to develop an efficient, expanded, and unambiguous locomotor rating scale to standardize locomotor outcome measures across laboratories. Adult rats (n = 85) were contused at T7-9 cord level with an electromagnetic or weight drop device. Locomotor behavior was evaluated before injury, on the first or second postoperative day, and then for up to 10 weeks. Scoring categories and attributes were identified, operationally defined, and ranked based on the observed sequence of locomotor recovery patterns. These categories formed the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. The data indicate that the BBB scale is a valid and predictive measure of locomotor recovery able to distinguish behavioral outcomes due to different injuries and to predict anatomical alterations at the lesion center. Interrater reliability tests indicate that examiners with widely varying behavioral testing experience can apply the scale consistently and obtain similar scores. The BBB Locomotor Rating Scale offers investigators a more discriminating measure of behavioral outcome to evaluate treatments after spinal cord injury. PMID- 7783231 TI - Plasma and cerebrospinal fluid concentrations of 4-aminopyridine following intravenous injection and metered intrathecal delivery in canines. AB - Potassium channel blockade by 4-aminopyridine (4-AP) has been shown to initiate modest levels of functional recovery in spinal-injured dogs and people following intravenous administration; however, the relevant central nervous system (CNS) concentration mediating these effects is not known. We have determined the concentrations of 4-aminopyridine in plasma and cerebrospinal fluid following intravenous administration (0.5 mg/kg) in large (> 22 kg) dogs, using liquid column chromatography. Plasma levels are initially high (> 1 microgram/mL) and fall rapidly to levels less than 100 ng/mL by about 2 h postinjection. A characteristic secondary peak in plasma 4-AP is observed at about 1 h postinjection. Corresponding concentrations of 4-AP in CSF were relatively stable for nearly 2 h, never exceeding (as a mean) 50 ng/mL within the first 2 h postinjection. We suggest behavioral recovery in clinical cases of spinal cord injury in both dogs and humans is mediated by such low (< 50 ng/mL) concentrations of 4-AP bathing the lesion. Since the adverse side effects that accompany IV administration of the drug limit its potential clinical usefulness, we have evaluated the feasibility of an alternate route of administration, continuous metered delivery of 4-AP into the spinal cord's subarachnoid space. This is accomplished by using a surgically implantable pump and delivery catheter. The pump itself can be interrogated, and is fully programmable, by noninvasive telemetry. Intrathecal delivery rates of between 1 and 60 micrograms of 4-AP per hour never produced detectable levels of the drug in plasma or cervically sampled CSF in dogs independent of the amount or duration of infusion (hours to days). The levels of 4-AP in lumbar samples of CSF near the lumbar delivery site suggest a very steep gradient of the drug, with local concentrations easily reaching 1 microgram/mL or higher (10- to 20-fold higher than can be safely produced by IV administration). The most frequent adverse reaction to intrathecal 4-AP delivery was a mild hindlimb tremor, fully reversible following reduction in the rate of drug delivery or termination of delivery. This route of drug administration relative to clinical spinal cord injury is discussed. PMID- 7783233 TI - Blood-brain barrier breakdown and edema formation following frontal cortical contusion: does hormonal status play a role? AB - The present experiment was designed to evaluate and correlate the time course of blood-brain barrier (BBB) integrity and cerebral edema in adult male rats given medial frontal cortex contusions. The effect of sex hormones on BBB integrity in the same injury model was also examined, because previous work has shown that progesterone can reduce cerebral edema (Roof et al., 1993). BBB breakdown was assessed by Evans blue extravasation and albumin immunostaining while edema formation was measured by the wet weight dry weight technique. These processes were examined beginning 2 h and continuing up to 10 days after injury. Our findings show that medial frontal contusion in rats produces changes in cerebral water content and opening of the BBB that endures at least 7 days postinjury. Although pseudopregnancy has been shown to reduce cerebral edema at day 1 postinjury, we did not find any evidence that this hormonal state is associated with BBB repair. PMID- 7783232 TI - Altered immunoexpression of microglia and macrophages after mild head injury. AB - In this study we examined the temporal response of microglia and macrophages to mild head injury in the rat. Microglia and macrophages were identified by their distinct morphology and by immunophenotype. With regard to the latter, antibodies to OX42 and ED1 were used to define microglia and macrophages, respectively. Although there was no change in the morphology of brain macrophages after mild head injury, the morphology of microglia was dramatically altered. Microglial cell bodies appeared larger with a more elaborate arborization of cellular processes. After head injury certain populations of macrophages and microglia were more intensely immunostained. By 3 days postinjury these intensely stained cells exhibited a characteristic distribution in the brain. Prominently stained microglia were detected in the thalamus, hippocampus, lateral and medial geniculate body, and the substantia nigra. Intensely stained macrophages were located primarily in the cortex and subarachnoid space adjacent to the site of impact. By 7 days postinjury intensely immunostained macrophages and microglia were widespread throughout the injured cortex. These results demonstrate that microglia and macrophages are sensitive to mild head injury. Early changes in the macrophage population are more directly correlated with the most damaged tissue and may reflect migration of these cells from either the subarachnoid space or across the damaged blood-brain barrier. The early widespread microglial response in regions exhibiting no overt neuronal cell damage suggests that these cells are responding to more subtle factor(s) that are expressed in the mildly traumatized brain. PMID- 7783234 TI - Effect of hypoxia or hyperbaric oxygen on cerebral edema following moderate fluid percussion or cortical impact injury in rats. AB - This study was designed to evaluate the production of cerebral edema [as measured by tissue specific gravity (SpG)] following moderate fluid percussion (FP) and cortical impact (CI) injury in rodents. To determine the effects of a secondary systemic insult, hypoxia (13% oxygen for 30 min) was added to some experimental groups immediately after head injury. To determine the effects of hyperbaric oxygen (HBO) on injured cortical tissue, additional animal groups were exposed to HBO (1.5 atm, for 60 min), beginning 4 h after head trauma. Both injury models produced equal amounts of tissue edema at the site of injury (mean SpG +/- SEM = 1.035 +/- 0.001), when measured 6 h posttrauma. There was no significant edema at the tissue sites immediately adjacent to the trauma sites. The addition of hypoxia to either injury system did not increase edema formation beyond that produced by injury alone. HBO reduced the water content of the trauma site in animals that had received FP, but not in animals receiving CI. We conclude that with the injury parameters used in this protocol, both FP and CI appear to produce focal cerebral edema at the site of trauma. Hypoxia does not worsen edema. HBO appears to reduce edema produced by FP, but not by CI. PMID- 7783235 TI - The effect of acute cocaine or lidocaine on behavioral function following fluid percussion brain injury in rats. AB - One of the goals of our laboratory is to examine how the presence of drugs of abuse will influence traumatic brain injury. Previous studies in our laboratory have shown that cocaine or lidocaine treatment before experimental fluid percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to determine if pretreatment with cocaine or lidocaine is also associated with changes in trauma-induced suppression of reflexes and motor and cognitive dysfunction that occurs following traumatic brain injury (TBI). Twenty-four hours after surgical preparation, rats were randomly assigned to a saline or drug pretreatment group, cocaine (0.5, 2, or 5 mg/kg) or lidocaine (2 mg/kg), which was injected via the tail vein. None of the drug pretreatments worsened injury. Lidocaine and cocaine decreased the duration of suppression of some neurological reflexes and reduced posttraumatic body weight losses. Lidocaine and cocaine both decreased postinjury motor deficits. Lidocaine and cocaine did not affect cognitive function on days 11-15 postinjury. The mechanism by which lidocaine improves acute neurological and motor function following brain injury is unknown, but may involve improved posttraumatic cortical blood flow, as seen in our previous study. Our results, along with other studies showing lidocaine to be neuroprotective in animal models of ischemia, suggest that studies of the effect of posttraumatic administration of lidocaine are warranted. PMID- 7783236 TI - Wrist strength measured by myometry as an indicator of functional independence. AB - The purpose of this study was to show that independence of self care activities of motor complete quadriplegic patients related better to the force of contraction of the wrist extensor (WE) muscles measured by a hand held myometer than to the manual muscle test (MMT) for grades 3 to 5. The patients (n = 24), identified by having unilaterally or bilaterally functional WE muscle (MMT > or = 3/5) with bilateral elbow extensor (EE) muscles < 3/5, were evaluated at 2 to 6 months after injury for four feeding activities utilizing the Quadriplegia Index of Function (QIF). We found 54% were independent drinking from a cup, 58% using a spoon or fork, 13% cutting food, and 23% pouring liquids. Comparisons were made between right, left, and bilateral mean myometry scores and median MMT scores for each of the QIF activities. The independent group of patients had myometry scores 54 to 140% greater (p < 0.05) than those patients dependent in the self care activity except when the right or left WE myometric score was analyzed for cutting food (p = 0.1). MMT comparisons showed no significant median score differences in any activity performed. There were no patients with only one WE muscle > or = 3/5 (n = 9) who were able to cut food or pour liquids independently. In conclusion, myometry appeared to be a better indicator than the MMT for some self care activities evaluated utilizing the Quadriplegia Index of Function. PMID- 7783237 TI - Acute low back problems in adults. Guideline overview. Agency for Health Care Policy and Research Rockville, Maryland. PMID- 7783238 TI - Health-care reform: a view from the National Medical Association. PMID- 7783239 TI - A new Provident Hospital. PMID- 7783240 TI - Outcomes in African-American women with suspected acute myocardial infarction: the Myocardial Infarction Triage and Intervention Project. AB - Increasing attention has been given to the investigation of cardiovascular disease in women, although African-American women have received little attention. This study compares characteristics and outcomes in women admitted to coronary care units for suspected acute myocardial infarction (MI). Between January 1988 and December 1991, a total of 554 (5%) African-American and 9738 (95%) white women with suspected acute MI were admitted to coronary care units in metropolitan Seattle, Washington. Relevant demographic socioeconomic, clinical, and outcome data were abstracted from the medical record and entered in the Myocardial Infarction Triage and Intervention registry. African-American women were younger, more often single and unemployed, and were less likely to have health insurance than their white counterparts. In addition, a higher proportion of African-American women reported a history of hypertension and diabetes mellitus. After adjustment for age, African-American women were equally as likely to develop acute MI and were more likely to die in the hospital. In addition, a higher proportion of African-American women were readmitted to coronary care units for suspected MI. Compared with their white counterparts, African-American women with suspected acute MI were considerably worse off from both socioeconomic and clinical standpoints, and their relative disadvantage was apparent in poor outcomes. PMID- 7783242 TI - Consumer product-related ocular trauma. AB - Leading causes of consumer product-related ocular trauma have not been well described. To delineate these causes in a nationally representative sample, data collected by the US Consumer Product Safety Commission (USCPSC) were reviewed. Data were obtained from the National Electronic Injury Surveillance System (NEISS), a national probability sample survey conducted by USCPSC that continuously monitors consumer product-related injuries treated in hospital emergency rooms across the United States. These data formulated the product summary report for the calendar year 1991. The sampling frame for the NEISS consisted of hospitals listed on the Center for Health Statistics Master Inventory File stratified geographically by size of hospital and number of emergency-room visits. During the calendar year 1991, there were a nationally estimated 298,852 consumer product-related eye injuries treated in hospital emergency rooms. Appoximately 500 different products were implicated in these injuries, with the leading cause being contact lenses (hard and soft), accounting for an estimated 26,490 emergency-room visits. This is followed by welding equipment (12,771 visits), hair curlers/curling irons (5946 visits), and workshop power grinders (5476 visits). Consumer products account for a sizable number of ocular injuries requiring treatment in hospital emergency rooms. Research on outcomes and prevention strategies of the injuries is warranted. PMID- 7783241 TI - Group A beta-hemolytic streptococcal bacteremia in a patient with sickle cell anemia on penicillin prophylaxis. AB - Serious invasive bacterial infections, particularly those due to Streptococcus pneumoniae and Hemophilus influenzae, are a well-known complication in patients with sickle cell disease. Early penicillin prophylaxis has been shown to prevent these infections and also to improve survival. This article describes a child with sickle cell anemia who, while on penicillin prophylaxis, developed a group A streptococcal bacteremia, a pathogen not commonly associated with bacteremia in sickle cell disease. PMID- 7783243 TI - Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles. AB - To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner city hospitals. PMID- 7783244 TI - Beyond controlling blood pressure in the black patient: metabolic considerations. AB - Hypertension is highly prevalent among African Americans, who are also more likely than whites to develop end-organ complications of hypertension. Traditional diuretic-based stepcare therapy has successfully reduced such complications of hypertension as stroke, congestive heart failure, and premature death in all populations tested. Prevention of coronary deaths has been less successful. Potentially adverse metabolic effects of thiazide diuretics and some beta-blockers may partially explain the less successful cardiac outcomes. Use of antihypertensive agents lacking adverse metabolic effects but still achieving effective blood pressure control could improve cardiac outcomes while maintaining the benefits achieved with older forms of therapy. Achievement of improved cardiac outcomes is now one of the principal goals of hypertension research and treatment. PMID- 7783245 TI - The natural history of homozygous S sickle cell anemia in two sisters. AB - This article describes the natural history of homozygous S sickle anemia in two sisters who have completely different morbidity patterns. Medical records beginning in May 1976 from the Urban League Sickle Cell program and my office, hospital records, and personal interviews were used. The sisters were older than 20 years when the diagnosis was made. Both had two essentially uneventful pregnancies, and neither was treated with prophylactic transfusions during the pregnancies. One sister has a hemoglobin F level of 23%, has been hospitalized only 15 times to date, and has no gallstones. The other sister has a hemoglobin F level below 3%, has been hospitalized more than 148 times to date, and had a cholecystectomy in 1979. Clinical symptoms in sickle cell patients with high levels of hemoglobin F is reportedly mild, and this has been supported by this study. Likewise, the conclusion by some investigators that prophylactic blood transfusions during pregnancy are unnecessary also has been supported. While many exciting investigative approaches relative to management and prevention of sickle cell anemia continue, it is equally important to maintain emphasis on the variables that encourage and facilitate positive psychosocial adaptations by these patients. PMID- 7783246 TI - Carpal tunnel syndrome: issues and answers. AB - Carpal tunnel syndrome has received a lot of attention recently in both the medical literature and the lay press. This is due, in large part, to increased recognition and treatment of this condition and its acceptance in the 1980s as being a work-related injury. The latter has been a source of confusion for patients and for many physicians, and signifies a real need for a clearer understanding of the entity known as carpal tunnel syndrome. This article addresses some of the current major issues regarding carpal tunnel syndrome and provides answers to those important issues. PMID- 7783248 TI - The Veteran's Hospital controversy. PMID- 7783247 TI - Profuse bleeding in epiphrenic diverticula: an unusual finding. AB - Profuse bleeding is an unusual and previously unreported finding in epiphrenic diverticula. The present case describes a man with a history of significant alcohol and tobacco abuse who presented to an emergency room expectorating blood and was then admitted. Further evaluation revealed a large bleeding ulcer crater in the distal esophagus. Findings consistent with candida esophagitis were noted on biopsy. Radiographic examination revealed two large, wide-mouthed diverticula. While hypertensive lower esophageal pressure was noted on manometric evaluation, surgery was not performed on the patient, and he subsequently curtailed his alcohol and tobacco intake. A follow-up examination at 90 days' postdischarge revealed no further bleeding episodes with continued decreased alcohol and tobacco intake. PMID- 7783249 TI - Role of alterations in Ca(2+)-associated signaling pathways in the immunotoxicity of polycyclic aromatic hydrocarbons. AB - Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. The effects of PAHs on the immune system of various animals and models have been studied for at least 30 yr. Despite these efforts, the mechanism or mechanisms by which PAHs exert their effects on the immune system are still largely unknown. During recent years, the molecular events associated with lymphocyte activation and receptor mediated signaling have become increasingly clear. Substantial progress has been made in understanding the molecular and cellular bases for toxicant-induced immune cell injury. Understanding mechanisms of drug or chemical effects on the immune system is an important area of research in the field of immunotoxicology, and indeed in all fields of toxicology. Mechanistic toxicology plays an important role in risk assessment and extrapolation of potential human health effects. In this review, we have summarized recent evidence that has examined the effects of PAHs on the immune system of animals and humans. In particular, we have focused on the effects of PAHs on cell signaling in lymphoid cells and have examined the hypothesis that PAHs alter lymphocyte activation via calcium-dependent mechanisms. Previously published reports are discussed, and new data obtained with murine B cells and cell lines are presented demonstrating the relationship between alterations in intracellular calcium and immune dysregulation. These data demonstrate a strong association between PAH-induced alterations in B- and T lymphocyte activation and changes in calcium homeostasis. PMID- 7783250 TI - A multidisciplinary approach to toxicological screening: I. Systemic toxicity. AB - The toxicity of 10 chemicals, including pesticides (carbaryl, chlordane, heptachlor, and triadimefon), solvents (carbon tetrachloride, dichloromethane, tetrachloroethylene, and trichloroethylene), and industrial chemicals [diethylhexylphthalate (DEHP) and phenol] was examined in the liver, kidneys, spleen, thymus, and adrenals of female F344 rats after 1 or 14 d of oral dosing. For each chemical, 4 doses were based on fractions of the acute LD50, which was estimated using an abbreviated (up-and-down) method. A multivariate analysis (MANOVA) was conducted for each organ using selected measures of toxicity. A post hoc contrast analysis was also conducted for significant MANOVA results in order to determine effective and ineffective doses. A single dose of heptachlor resulted in necrotic lymphocytes in the spleen and thymus at doses > or = 23 mg/kg. Triadimefon altered liver and spleen weights; this effect has not been described previously. Dichloromethane (> or = 337 mg/kg/d for 14 d) increased the incidence of necrosis of individual centrilobular hepatocytes. Trichloroethylene induced hepatotoxicity was obtained at doses an order of magnitude lower than those reported in the literature. Acute DEHP (150 mg/kg) increased mitotic figures in hepatocytes, which were replaced by hepatocellular cytomegaly after 14 d of dosing at the same level. Following phenol exposure, there was an increased incidence in hepatocellular necrosis at 1 d, and an increased incidence of kidney lesions at 1 and 14 d; these findings were considered to be the result of vascular stasis. Overall, the algorithm used to select doses was effective for both 1- or 14-d dosing regimens. For all chemicals except carbon tetrachloride, the lowest effective dose for systemic toxicity was within the range of 3-56% of the LD50 for acute dosing, and 1-30% of the LD50 for repeated administration. PMID- 7783251 TI - A multidisciplinary approach to toxicological screening: II. Developmental toxicity. AB - As part of the validation of an integrated bioassay for systemic toxicity, neurotoxicity, and developmental toxicity, we evaluated the effects of four pesticides, four chlorinated solvents, and two other industrial chemicals in Fischer 344 rats. The pesticides included carbaryl, triadimefon, chlordane, and heptachlor; the solvents included dichloromethane (DCM), carbon tetrachloride, trichloroethylene (TCE), and tetrachloroethylene (perchloroethylene, PER); and the industrial chemicals were di(2-ethylhexyl)phthalate (DEHP) and phenol. In the developmental toxicity studies, timed-pregnant rats were treated by gavage with vehicle or 1 of 2 dose levels of each compound on gestation d 6-19. The dams were allowed to deliver and their litters were examined on postnatal d 1, 3, and 6. Litter weights were determined on postnatal d 1 and 6. Implants were also counted to determine prenatal loss. Maternal toxicity was evidenced by dose-related alterations in weight gain for all 10 compounds. Clinical signs of maternal toxicity were present for all chemicals except chlordane and heptachlor. DEHP exposure resulted in the most pronounced developmental toxicity (high levels of pre- and postnatal mortality), whereas chlordane induced extensive postnatal loss. Of the solvents, only DCM did not cause a high incidence of full-litter resorption. Phenol, heptachlor, triadimefon, and carbaryl showed only slight potential for developmental toxicity. Malformations suggestive of teratogenicity included kinked tail (phenol), microphthalmia (TCE, PER, DEHP), and cleft palate with renal agenesis (DEHP). Although several findings (eye defects caused by TCE and PER, full-litter resorption and delayed parturition caused by PER, and delayed parturition/dystocia associated with triadimefon) have not been previously reported, the results are generally consistent with previous reports and highlight the importance and relative ease of incorporation of developmental evaluations into a multidisciplinary screening battery. PMID- 7783252 TI - A multidisciplinary approach to toxicological screening: III. Neurobehavioral toxicity. AB - The neurobehavioral effects of 10 known toxicants were examined as part of a multidisciplinary screening battery. The toxicants included carbaryl (CAR), triadimefon (TDM), heptachlor (HEP), chlordane (CDN), diethylhexyl phthalate (DEHP), carbon tetrachloride (CCl4), phenol, trichloroethylene (TCE), tetrachloroethylene (PER or perchlorethylene), and dichloromethane (DCM or methylene chloride). A functional observational battery and motor activity measurements were conducted before exposure, at specified times after an acute exposure, and during and after 14-d exposure. Severity scoring analysis was used to generate profiles of effect. The pesticides, CAR, TDM, HEP, and CDN, displayed the most acute neurotoxicity and were active at lower proportions of their respective acute LD50 values than were the solvents or the industrial chemicals. Although CAR and TDM showed little or no neurobehavioral effects with repeated dosing, cumulative neurotoxicity and lethality were evident with HEP and CDN. Phenol produced acute convulsive effects, and the most prominent finding with repeated exposure was lethality. DEHP displayed no neurobehavioral toxicity. The organic solvents, TCE, PER, CCl4, and DCM, produced various degrees of general nervous system depression following acute administration of high dose levels. Repeated dosing produced little or no effect with TCE or PER, marked physiological changes with CCl4, and cumulative toxicity and lethality with DCM. Some results of these studies were unexpected and should provide impetus for further research. Overall, these findings illustrate the utility of these screening methods. PMID- 7783253 TI - A multidisciplinary approach to toxicological screening: IV. Comparison of results. AB - Toxicity data collected under standardized test conditions may be of the utmost importance in health risk assessment, in which human exposure limits are often derived from laboratory experiments. A standardized approach to data collection is also important for evaluating the sensitivity and specificity of test methods used to determine toxic potential. Several experiments were undertaken to determine the effects of chemical exposures using a multidisciplinary screening battery, which included tests for systemic, neurological and developmental toxicity. The effects of 1- and 14-d exposures to 10 chemicals on systemic and neurological indices of toxicity were determined in female F344 rats using standardized test batteries. Parallel experiments determined chemical effects on prenatal and postnatal development following exposure of the dams for 14 d. The chemicals included four pesticides (carbaryl, triadimefon, chlordane, and heptachlor), four solvents (trichloroethylene, tetrachloroethylene, carbon tetrachloride, and dichloromethane), and two industrial compounds (phenol and diethylhexyl phthalate). The results showed that the chemicals produced markedly different qualitative patterns of effect on systemic, neurological, and developmental indices of toxicity. Differences in the pattern of systemic and neurological effects were also obtained that depended on dosing duration. Quantitative analyses indicated that the highest ineffective dose as well as the lowest effective dose could vary by as much as two orders of magnitude across the different indices of toxicity. These results clearly show that a test battery focused on a single endpoint of toxicity cannot be used to accurately predict either qualitatively or quantitatively a chemical's systemic, neurological, and developmental toxicity profile. PMID- 7783254 TI - Neurobehavioral and physiologic effects of trifluoromethane in humans. AB - Nuclear magnetic resonance (NMR) imaging shows promise in the measurement of human cerebral blood flow (CBF) in that nonradioactive indicators may be used. Our earlier investigations with trifluoromethane (FC-23) gas have shown that this compound can be used to safely and effectively measure CBF in anesthetized animal models. In this Phase I dose-escalation study we set out to determine the maximal tolerated concentration (MTC) of FC-23 in normal healthy male volunteers and to assess its feasibility as an NMR indicator. Five subjects were exposed in a blinded fashion to escalating concentrations of FC-23 between 10% and 60%, randomly interleaved with exposures to both room air and 40% nitrous oxide. On each study day, the subjects breathed the test gas for eight pulses of 3 min each with 2-min clearance periods between the pulses. The subjects underwent intensive physiologic and neurobehavioral monitoring throughout the study period. The first subject experienced an anesthetic response to 60% FC-23, and the second subject experienced "discomfort" and requested discontinuation at the initiation of 40% FC-23. The MTC was subsequently determined to be 30% FC-23 (all subjects tolerated the gas), although a small (37.6 vs. 40.5) but statistically significant retention of carbon dioxide was found (p = .003). When one subject received 30% FC-23 during an NMR imaging study, a pronounced anesthetic effect with intolerable hyperacusis was demonstrated. Human studies of FC-23 have been discontinued in our laboratory. PMID- 7783255 TI - Effect of radiofrequency catheter ablation on calcium channel of ventricular myocytes. AB - Using whole-cell patch-clamp technique, the effect of radiofrequency catheter ablation (RFCA) on calcium current (Ica) of guinea pig ventricular myocytes was examined. The radiofrequency energy delivered was 20 W x 10 s. RF-CA decreased Ica apparently with the affected area reaching up to 1.2 cm from the ablation focus. In the meanwhile, the pathological lesion size resulted from RFCA was merely 0.41 +/- 0.11 cm. These findings indicate that RFCA, apart from causing tissue necrosis by heat, can affect myocyte membrane currents in a large area. This may explain why RFCA has a very high success rate with a small pathological lesion. PMID- 7783256 TI - Study on three dimensional reconstruction of transesophageal echocardiographic images. AB - Using biplane transesophageal echocardiography and the concept of three dimensional transthoracic echocardiography, we performed three dimensional reconstruction of transesophageal images of various clinicopathologic cases, including atrial septal defect, mitral stenosis, mitral valve prolapse and pulmonary stenosis. The hardware equipment and image processing flow chart of three dimensional reconstruction of transesophageal echocardiographic images are described. Our present study indicates that three dimensional reconstruction of transesophageal echocardiographic images could display multi-regional three dimensional structures of heart and great vessels, including superior vena cava, ascending aorta, right ventricular outflow tract, pulmonary artery and left heart, with clear, visual and stereoscopic imaging. The regional structures could be displayed at different levels of stereo-anatomic-sections and in different orientations of rotating stereo-images, which could provide accurate three dimensional anatomical information for cardiac stereo-morphological study and definition of spatial location and size of cardiac abnormalities. PMID- 7783257 TI - Role of the pericytes of intra-acinar pulmonary artery in the structural remodeling of pulmonary vessels. AB - Whether or not the pericytes exist in the intra-acinar pulmonary arteries and their normal structure and morphological changes during development of the structural remodeling of pulmonary vessels were observed using a pulmonary hypertension model in rats induced by monocrotaline injection. The results showed that the pericytes in the peripheral pulmonary vessels proliferated and transformed into smooth muscle cells during development of pulmonary hypertension, and at the same time, the pericytes could synthesize and secrete extracellular matrix including collagen, suggesting that the pericytes play an important role in the development of pulmonary hypertension and structural remodeling of the pulmonary vessels. PMID- 7783258 TI - [Neuron-specific enolase: a serum marker of clinical progression for metastatic malignant melanoma]. PMID- 7783260 TI - Observations on therapeutic effects of huangdan decoction and Tripterygium Wilfordii compound tablet on membranous glomerulonephritis in rats. AB - The model of membranous glomerulonephritis (MGN) in rats was successfully established using self-made cationic bovine serum albumin (C-BSA) and treated with Huangdan Decoction (HDD) and Tripterygium Wilfordii Co. tablet (TW). Results indicated that the levels of urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) in treated groups (groups A, B and C) were significantly decreased as compared with the control group (group D) (P < 0.01). By light and electron microscope and immunofluorescent technique, the damage to kidney in groups A, B and C was found much milder than that in group D with lesion in group A being slightest. These findings suggest that HDD and TW may alleviate the pathological lesions of MGN, prevent or retard its progression, and have remarkable therapeutic effects on MGN. PMID- 7783259 TI - Effects of 3,4-dihydroxyacetophenone (3,4-DHAP) on hypoxic pulmonary and systemic vascular response in dogs. AB - The effects of 3,4-DHAP on hypoxic pulmonary and systemic vascular responses were studied in anaesthetized dogs. The percentage change in pulmonary vascular resistance (delta PVR %) and that in systemic vascular resistance (delta SVR %) induced by 5 min hypoxia decreased significantly. 3,4-DHAP in doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg i.v. caused a decrease in delta PVR% from the control value of 47.27 +/- 22.27% to 24.62 +/- 21.76%, 18.15 +/- 18.73%, and 24.10 +/- 19.76% respectively, and a decrease in delta SVR % from the control value of 12.91 +/- 7.39 % to -0.34 +/- 12.70%, -2.11 +/- 12.76%, and -2.37 +/- 15.52 % respectively. The results showed that 3,4-DHAP could decrease the hypoxic responses of pulmonary and systemic blood vessels. But it did not change delta PVR % or delta SVR % in dose of 30 mg/kg, neither did it influence the heart rate, cardiac output or cerebral blood flow during hypoxia in all the doses used. PMID- 7783261 TI - Effect of huoxuequyu recipe on erythrocyte membrane Ca(2+)-ATPase activity in pregnant rats with asymmetrical intrauterine growth retardation induced by passive smoking. AB - The effect of Huoxuequyu recipe on erythrocyte membrane Ca(2+)-ATPase activity in pregnant rats with passive smoking induced asymmetrical intrauterine growth retardation (IUGR) was observed. The rats were divided into three groups: control group, model group and treated group. The fetal mean birth weight and erythrocyte membrane Ca(2+)-ATPase activity were found to be decreased in the model group as compared with the control and treated groups. There was a significant difference between the model group and the control group (P < 0.01), while no significant difference existed between the treated group and the control group (P > 0.05). Furthermore, the findings indicated that the erythrocyte membrane Ca(2+)-ATPase activity seem to be positively correlated with the birth weight (P < 0.05). On the basis of our observation, it is believed that the Huoxuequyu decoction could increase erythrocyte membrane Ca(2+)-ATPase activity and promote blood circulation, thereby exerting a beneficial effect on fetal development. PMID- 7783262 TI - Experimental study of corneal innervation in diabetic mellitus. AB - The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes. The experimental rabbits were killed after 6, 8, 10, 12 weeks. Corneal innervation was studied by histochemical techniques and transmission electron microscopy. The results revealed that in diabetic rabbits, from 6 weeks, the density of nerve-nets was markedly sparser, the fibers were thinner and the activity of nerves was lower than those of the control group. Ultrastructural changes showed swelling of axons, irregular distribution of fibril and degeneration of mitochondria of varying degree. With the progress of disease the above changes were becoming more marked gradually. It may be assumed that these changes are related to hyperglycemia. PMID- 7783263 TI - Microcomputer system for automatic identification of the Cryptococcus neoformans and its clinical application. AB - In this study, microcomputer image processing and pattern recognition technology, and the knowledge of morphology and optical characteristics of Cryptococcus neoformans were used for identification of Cryptococcus neoformans. Four groups of mice were lethally infected with standard strain, Wuhan strain, American B 2643 strain and Var. Shanghainesis of the Cryptococcus neoformans. The samples collected included mice brain, lung, kidney, liver, small intestine tissue and were observed under a light microscope. More than 600 images of the fungus were input into a microcomputer. A system of computer for automatic identification of the Cryptococcus neoformans was developed. The technique involved image preprocessing, image segmenting, coding of line-length on the edge, curve fitting, extracting of image feature, building of image library and feature data bank etc.. And then, 768 images of the clinical samples and other fungus samples whose morphological features tend to be confused with Cryptococcus neoformans were input into microcomputer and subjected to automatic identification. The Cryptococcus neoformans was accurately identified within 15 min, and the consistency rate with results of routine culture was 98%. PMID- 7783264 TI - [Experimental studies of embolization of different hepatotropic blood vessels using Bletilla striata in dogs]. AB - Bletilla striata and gelfoam were used as embolizing agents for the embolization of various hepatotropic vessels in dogs. The results proved that Bletilla striata was superior to gelfoam. The mechanisms of embolization by Bletilla striata are attributable to following factors: non--absobent property, mechanical obstruction; effects on coagulative and anticoagulative systems and secondary obstruction resulted from the injury to wall of blood vessels. PMID- 7783265 TI - A new model of experimental cerebral infarction in New Zealand white rabbits. AB - To develop an easy, reproducible experimental model of cerebral infarction (CI) without craniotomy in New Zealand white rabbits, a silicone rubber cylinder embedded in a nylon suture was delivered to the middle cerebral arteries through the internal carotid artery in anesthetized animals. Rabbits were sacrificed 0.5 5 h after embolization. CI size and location were ascertained by the triphenyl-2H tetrazolium chloride (TTC) staining method; cerebral blood flow (CBF) was measured prior to and after embolization. PCO2, temperature and blood pressure were monitored and kept constant. CI occurred in all rabbits after 4 h of ischemia, in 50% after 3 h and only in 33% after 2.5 h. CI did not occur within less than 2.5 h of ischemia. No correlation was found between size and location of CI and occlusion time. CBF was maximally reduced in the right MCA territory but was also reduced in both anterior cerebral arteries and left MCA territories. This model is technically easy and the retrievable embolus allows the study of reperfusion by pulling on the nylon suture. It is suitable for studying chemical and molecular changes of the ischemic cells and/or for studying neuroimage changes after ischemic stroke. PMID- 7783266 TI - Studies on the role of sodium/hydrogen exchange system in myocardial ischemia reperfusion injury. AB - This study aimed at the exploration of the relationship between Na(+)-H+ exchange system and myocardial ischemia-reperfusion injury (MRI) in an attempt to provide a theoretic basis for the prevention and treatment of MRI. We used the isolated working guinea pig hearts as the experimental model to mimick cardiopulmonary bypass, which included 120 min hypothermic ischemic cardioplegic arrest followed by 60 min normothermic reperfusion. The hearts were divided into 2 groups: the control group receiving St. Thomas' Hospital Solution (STS) and the treated group receiving STS + amiloride, a Na(+)-H+ exchange blocker. The results showed that during reperfusion, [Na+]i and [Ca2+]i overloads, poor recovery of cardiac function, increases in CPK release and OFR generation, reduction of ATP content and serious damage of ultrastructure were seen in group 1; whereas there were no [Na+]i and [Ca2+]i overloads and better recovery of cardiac function accompanied by improved results of biochemical assay and less damage of ultrastructure was found in group 2. Our study indicates that amiloride can inhibit Na(+)-H+ exchange system in cardiac cells during early reperfusion period, which prevents [Na+]i overload produced by Na(+)-H+ exchange, and stops Na(+)-Ca2+ exchange activated by high level of [Na+]i, thus attenuating [Ca2+]i overload caused by Na(+)-Ca2+ exchange and myocardial injury. Therefore, we conclude that Na(+)-H+ exchange blocker, amiloride, can exert significant protective effects on MRI and its use may prove to be a new clinical approach to prevention and cure of MRI. PMID- 7783267 TI - Portal vein embolization with lipiodol for treatment of HCC--an experimental study. AB - A suspension of iodized oil and anticancer agent was injected into the portal veins of 20 rats with hepatic carcinoma. Oil drops were seen in tumor cell lines, small blood vessels inside the cancer nest, the sinusoid, and the central veins. After injection of oil suspension through the portal vein the distal small vessels were embolized and necrotic changes of tumor cells and their subordinate normal liver cells were observed. The results obtained in this experiment provided a good anatomical and pathological basis for treating liver cancers with the portal vein embolization with chemotherapeutic agents. PMID- 7783268 TI - [An epidemiological study on the relationship between musculoskeletal disorders and work load]. AB - 965 workers engaged in working tasks of work intensity grade 2, 3, 4 (based on Chinese National Standard) were investigated on the musculoskeletal disorders with a questionnaire. The lumbar vertebra of 136 randomly chosen workers were also radiologically examined. The result revealed that the prevalence of low-back disorders was 51.2% on average and it was obviously correlated with such factors as age, standing, previous back injury, education level, sport activity, work intensity, working posture, satisfaction with the tools as well as work condition and house work. Heavy work load and unneutral working posture were proved to be the main factors as revealed by the multifactor analysis and further supported by the findings of X-ray examination. PMID- 7783269 TI - A common-source outbreak of shigellosis involving a piped public water supply in northern Thai communities. AB - We report an epidemiological investigation of an explosive common-source water borne shigellosis outbreak traced to a piped public water system in northern Thai communities. In August 1991, 242 cases of acute diarrhoeal illness occurred in Sam Ngao Subdistrict, Tak Province. About 30% of the cases were culture-positive for multiresistant Shigella flexneri 2a. The outbreak affected all age groups, with the highest attack rate (9.4%) in children < 5 years old. The first ten cases occurred during 1 and 5 August 1991 and a subsequent 158 cases (65.3%) clustered between 6 and 10 August 1991. Most cases (93.0%) occurred in the villages sharing the common piped water system A. The inhabitants who were served by system A had a significantly (P < 0.01) higher attack rate of infection (7.0%) than those who used the other piped public water system B (0.1%) or well water (0.3%). A case-control study revealed a significant association between disease and drinking unboiled piped water (P < 0.05, odds ratio 2.8). The implication of piped water was supported by the presence of faecal contamination in the piped water system, the result of interrupted chlorination. Rapid identification of the possible transmission source and prompt implementation of control measures curtailed the spread of this outbreak. PMID- 7783270 TI - Application of dot-immunogold-silver staining in the diagnosis of clonorchiasis. AB - All 35 confirmed clonorchiasis cases showed a positive reaction in dot-immunogold silver staining (Dot-IGSS) with a mean serum titre of 1:1656, while none of the sera from 35 normal individuals reacted. A seroepidemiological survey of middle school students revealed a positive rate of 17.0% (142/836), and 76.1% (105/138) of the serologically positive students were egg positive in stool examination. The egg positive rates in those with antibody at levels of 1+ to 4+ were 57.1% (28/49), 75.7% (28/37), 94.7% (36/38) and 92.9% (13/14) respectively. It is believed that Dot-IGSS can be used for the clinical diagnosis and epidemiological survey of clonorchiasis. PMID- 7783271 TI - A study of neonatal deaths at the Ogun State University Teaching Hospital, Sagamu, Nigeria. AB - A two-year prospective study of neonatal deaths at a Nigerian University Teaching Hospital is presented. There were 55 deaths among 1081 inborn live deliveries (50.88/1000). Low birthweight babies accounted for 60% of deaths. There were 49 (45.33/1000) perinatal deaths, 61% of which occurred within 24 hours. The mortality rate of term small-for-gestational age neonates was higher than that of their appropriate-for-gestational age counterparts (chi 2 = 4.55, P < 0.05). The mortality rate for 315 referred admissions was 400/1000. Referred very low birthweight babies had a better outcome than inborn ones. Severe infections, severe birth asphyxia, respiratory distress syndrome and recurrent apnoea were among the leading causes of death in this study. There is a need for improved intensive care facilities for the high-risk newborn. Greater effort is required to improve early utilization of available maternity services. PMID- 7783272 TI - Prevalence and presentation of hepatitis C related chronic liver disease in southern India. AB - To determine the importance of hepatitis C virus (HCV) infection in the aetiology of chronic liver disease in southern India, the prevalence of HCV antibodies and HBV markers was estimated in 100 patients with chronic liver disease and in 56 patients with a variety of other gastrointestinal and liver diseases who served as controls. HCV antibody was measured by a second-generation ELISA. HBsAg, anti HBc, anti-HBs and anti-D were also estimated. HCV antibodies were detected in 26/100 patients with chronic liver disease compared to 0/56 controls. HBV markers were present in 72 of 100 patients with chronic liver disease compared to 21/56 (37.5%) controls. Anti-D was noted in 4/100 patients with chronic liver disease and in none of the controls. Many patients had serological evidence of both B and C infection; 73% of those with anti-HCV also tested positive for HBV markers. HCV related disease presented at a median age of 60 years compared to HBV related disease which presented at a median age of 40. There was no significant difference between HCV and HBV positive patients in symptomatology, but encephalopathy was uncommon and cirrhosis the usual finding at histology in HCV positive individuals, while chronic active hepatitis was found in 30% of biopsied HBV related disease. HCV is a significant cause of chronic liver disease in this geographic region, although HBV infection continues to account for the largest proportion of cases. PMID- 7783273 TI - Platelet function studies in Indian kala-azar. AB - Platelet function studies were conducted on 25 parasitologically positive cases of Indian kala-azar and 25 age and sex matched healthy controls. Ninety-two per cent of patients had thrombocytopenia of variable degree; in 44% of patients, platelets were less than 60,000 mm-3. The platelet adhesive index was less than 30% in 70% of patients with kala-azar (normal 31-60%). Platelet aggregation time with ADP and adrenaline was abnormally prolonged compared to the controls. Platelet factor III availability was poor in 40% of cases. There was a fair degree of correlation between platelet adhesiveness and platelet factor III availability in these patients: 50% of patients with poor platelet adhesiveness showed reduced platelet factor III availability. PMID- 7783274 TI - Use of fundal height as a proxy for length of gestation in rural Africa. AB - Lack of information on the date of the last menstrual period is a common problem in antenatal care in developing countries. The aim of this study was to see whether the fundal height can be used as a proxy for the length of gestation. A graph representing the expected remaining time to delivery was constructed from fundal height measurements in 7790 pregnant women delivered in a rural African hospital from 1970 to 1988. The graph was used to predict the probable week of delivery in 604 pregnant women giving birth to a singleton child in 1989. The mean deviation of the actual week of delivery from the predicted week was -0.6 (s.d. 3.4) weeks. In 270/604 cases (45%) delivery occurred within 2 weeks of the predicted week. Birthweight and perinatal mortality were strongly related to the deviation from the predicted week of delivery. The majority of perinatal deaths (34/50, 68%) occurred in children delivered early. The fundal height, as measured by paramedicals in routine antenatal care in rural Africa, may be used as a proxy for the length of gestation when the date of the last menstrual period is not known. PMID- 7783275 TI - Coxiella burnetii antibody prevalences among human populations in north-east Africa determined by enzyme immunoassay. AB - Retrospective serosurveys were conducted to determine the prevalence of antibody to phase-I Coxiella burnetii among humans in various locations of north-east Africa. Sera were tested by the enzyme immunoassay (EIA). Initially the EIA was compared with the standard indirect fluorescent antibody (IFA) method for the detection of antibody to C. burnetii. Results indicated that the EIA was slightly less sensitive (88%), but highly specific (94%) and less subjective than the IFA technique. EIA was subsequently adopted for estimating prevalences in the studied human populations. Data obtained by EIA indicated that the prevalence of C. burnetii antibody among adult Egyptian blood donors was 20% (n = 358) in the Suez Canal area, 16% (n = 501) in the Nile Valley and 10% (n = 427) in the Nile Delta. Among adult patients with acute, undifferentiated fever in Egypt, the prevalence was 28% (n = 50) of acute sera, with seroconversion in 12% of convalescent sera. Antibody to C. burnetii was detected by EIA in the sera of 25% (n = 71) of cattle workers in Egypt, 10% (n = 100) of housewives in Sudan, and 37% (n = 104) of adults in north-west Somalia. Following a fever outbreak affecting all ages in northern Sudan, IgG antibody to C. burnetii was present in 54% of the febrile persons (n = 185) and in 53% of afebrile persons (n = 186). IgM antibody to C. burnetii was demonstrated in 29% of the febrile persons and 15% of the afebrile persons. These results implicate C. burnetii as a possibly important and under reported cause of human disease and undiagnosed fevers in north-east Africa. PMID- 7783276 TI - Tetanus: a recurring intensive care problem. AB - A fifteen-year retrospective study of 108 cases of tetanus admitted to the Intensive Care Unit (ICU) at the University Hospital of the West Indies is presented. Males predominated (70%), with peak incidence occurring amongst the young and the elderly. In 57% the disease was severe enough to require neuromuscular blockade and controlled ventilation. Respiratory complications occurred most commonly (80%), predominantly as a result of infection. Dysautonomia, exhibited by 55% of patients, presented the greatest difficulty in management. Mortality was high (20%), with sudden cardiac arrest being the most common cause of death. The average duration of stay in the ICU was long (27 days). As Jamaica is a Third World country with limited resources, the continued occurrence of this preventable disease represents a drain on existing intensive care funds. This must be brought to the attention of institutions responsible for planning health care programmes for developing countries. PMID- 7783277 TI - Epidemiology of human brucellosis in southern Saudi Arabia. AB - There have been indications that human brucellosis is widely distributed in Saudi Arabia. In order to assess the situation in the south, and as a part of a nationwide prevalence survey, a sample of 4900 subjects was randomly selected for a house-to-house survey. Investigations included an interview, clinical examination and blood sampling for antibody titre determinations. Blood samples were first screened for Brucella antibodies by a microplate agglutination test to measure the exposed rate. Reactive sera were further analysed by the standard tube agglutination and 2-mercaptoethanol tests. A total of 4794 completed the study. Results of laboratory tests indicated that a significant proportion of the population in the southern region (19.2%) had serological evidence of exposure to Brucella antigen, and 2.3% had active disease. Direct contact with domestic animals and consumption of raw products of animal origin were identified as the main risk factors. PMID- 7783278 TI - A chronic cavitary pulmonary histoplasmosis case from Turkey. AB - Histoplasmosis, a disease endemic to North America, is caused by Histoplasma capsulatum. To the best of our knowledge, the chronic cavitary pulmonary histoplasmosis patient described here presents the first case in which the fungus was isolated from sputum culture in Turkey. PMID- 7783279 TI - Malaria and filariasis transmission in a village/forest setting in Baram District, Sarawak, Malaysia. AB - Entomological investigations on malaria and bancroftian filariasis transmission were carried out in the endemic area of Baram District, Sarawak. The Anopheles composition, survival and infection rates of malaria and filariasis were compared in the village and 0.5 km from the village ecotype, in forested areas. Anopheles leucosphyrus, An. barbirostris and An. donaldi are the vectors for malaria and bancroftian filariasis in both ecotypes. Biting and infection rates vary, but An. leucosphyrus differed with a peak around midnight in the forested area and soon after dusk in the village setting. The parous rate of An. leucosphyrus was significantly higher in the forest ecotype (P < 0.0001); however, the proportion of 3-parous and older was not overall higher in the forest ecotype (P = 0.68). The entomological inoculation of malaria parasites by An. leucosphyrus was comparatively higher in the forested areas (P > 0.5). The implications of malaria and filariasis transmission in the forested areas in Baram District are discussed. PMID- 7783280 TI - Urban schistosomiasis in Lusaka, Zambia: a preliminary study. AB - A preliminary survey was conducted in Lusaka, Zambia to determine the extent of schistosomiasis transmission in the city. Stool and urine samples were collected from 240 children from seven schools selected to give a cross-sectional representation of the various socio-economic neighbourhoods of the city. In addition to the parasitological examination, students were questioned with respect to their knowledge of the disease and other epidemiological factors. In addition, water bodies near the schools were examined for the presence of snail hosts. Results of the survey suggest that schistosomiasis is actively transmitted within Greater Lusaka. An overall prevalence of 20.9% for S. haematobium was observed, but only one case of S. mansoni was detected. Prevalence rates for S. haematobium in individual schools ranged from 7.5 to 37.5%. PMID- 7783281 TI - Early childhood survivorship in Vietnam. AB - The effects on early childhood mortality of birth order, age of the mother at the time of the child's birth, mother's education, as well as infant mortality risk in the province, urban/rural residence, the presence of schools and other facilities and health care services, were examined using data from the 1988 Vietnam Demographic and Health Survey and the 1990 Study of Accessibility of Contraceptives in Vietnam. A total of 4137 urban and rural children born between 1983 and 1988 to the 4172 women interviewed in the Demographic and Health Survey were included in the hazard model analysis of maternal and child characteristics. However, since the Accessibility of Contraceptives Study included only rural respondents, the hazard model analysis of community development characteristics and health services effects on early childhood mortality was based on a subsample of 3314 rural children. Rural children in birth orders five and higher had the greatest risk of early childhood death, birth order one an intermediate risk and orders 2-4 the lowest risk of early childhood death. Rural children residing in communes with fewer than 10,000 inhabitants were at significantly greater risk of early childhood death than children from larger communes. Neither age nor education of the mother nor gender of the child, had a significant impact on early childhood survivorship independent of other variables. Risk of infant mortality in the child's province was of borderline significance. PMID- 7783282 TI - Alexandre Yersin and the plague bacillus. AB - To most doctors, the name Yersin is known only for its eponymous connection with the plague bacillus, Yersinia pestis. In Vietnam, where he lived for over 50 years, Alexandre Yersin is a legendary figure. On the 100th anniversary of the identification of the plague bacillus, a review of this extraordinary man and his controversial discovery is timely. PMID- 7783283 TI - Pathologists request autopsy revival. PMID- 7783284 TI - Silver anniversary celebrated for Penn State heart. PMID- 7783285 TI - Acellular pertussis vaccine scores high in trial. PMID- 7783286 TI - Tougher on tattoos. PMID- 7783287 TI - From the Health Care Financing Administration. PMID- 7783288 TI - From the Food and Drug Administration. PMID- 7783289 TI - From the Centers for Disease Control and Prevention. Reptile-associated salmonellosis--selected states, 1994-1995. PMID- 7783290 TI - Binge drinking in college. PMID- 7783291 TI - Binge drinking in college. PMID- 7783292 TI - Heart failure practice guidelines: guidance, not proscription. PMID- 7783293 TI - False-positive benzodiazepine urine test due to oxaprozin. PMID- 7783294 TI - Medical devices: significant vs non-significant risk. PMID- 7783295 TI - Medical devices: significant vs nonsignificant risk. PMID- 7783296 TI - Public attitudes toward autopsy, organ donation, and dissection. PMID- 7783297 TI - A food-borne outbreak of expensive antibiotic use in a community teaching hospital. PMID- 7783298 TI - Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. PMID- 7783299 TI - Reform of child immunization service delivery in Israel. PMID- 7783300 TI - Adolescents' perceptions of factors affecting their decisions to seek health care. AB - OBJECTIVE: To have adolescents, rather than adults, identify characteristics of health care providers and sites that affect their decision to seek care. DESIGN: Five stages conducted over a 10-month period: (1) focus groups to frame the study questions; (2) nominal group technique to generate student responses; (3) three surveys to assess response importance; (4) one survey to link the most important responses with the decision to seek care; and (5) focus groups to explain the variables associated with the decision to seek care. SETTING: The Philadelphia (Pa) School District. PARTICIPANTS: The study population consisted of all ninth graders from 39 of Philadelphia's 42 public high schools. The 6821 students who returned the final survey comprised the study sample (69% of in-school youth). RESULTS: In the final survey, students used a Likert scale (1 to 5) to describe the impact of 31 ideas on their decision to seek care. The most important characteristics were provider hand washing, clean instruments, honesty, respect toward teens, cleanliness, know-how, carefulness, experience, seronegativity for the human immunodeficiency virus, equal treatment of all patients, and confidentiality. There was little variation in the order of the items by sex, race, or socioeconomic status. Factor analysis showed that the most important of four identified latent factors related to infection control and provider competency. CONCLUSION: Four of the top 10 characteristics that affect an adolescent's decision to seek care involve cleanliness and infection control. These findings offer providers and planners straightforward, modifiable factors that teens believe influence their decision to seek care. PMID- 7783301 TI - The role of coronary angiography and coronary revascularization before noncardiac vascular surgery. AB - OBJECTIVE: To determine whether preoperative coronary angiography and revascularization improve short-term outcomes in patients undergoing noncardiac vascular surgery. DESIGN: Decision analysis. PATIENTS: Patients undergoing elective vascular surgery who had either no angina or mild angina and a positive dipyridamole-thallium scan result. INTERVENTIONS: Three strategies were compared. The first strategy was to proceed directly to vascular surgery. The second was to perform coronary angiography, followed by selective coronary revascularization, before proceeding to vascular surgery and to cancel vascular surgery in patients with severe inoperable coronary artery disease (CAD). The third was to perform coronary angiography, followed by selective coronary revascularization, before proceeding to vascular surgery and to perform vascular surgery in patients with inoperable CAD. MAIN OUTCOME MEASURES: Mortality, nonfatal myocardial infarction, stroke, uncorrected vascular disease, and cost. All outcomes were assessed within 3 months. RESULTS: Proceeding directly to vascular surgery led to lower morbidity and cost in the base case analysis. The coronary angiography strategy led to higher mortality if vascular surgery would proceed in patients with inoperable CAD, but led to slightly lower mortality if vascular surgery were canceled in patients with inoperable CAD. The coronary angiography strategy also led to lower mortality when vascular surgery was particularly risky. CONCLUSIONS: Decision analysis indicates vascular surgery without preoperative coronary angiography generally leads to better outcomes. Preoperative coronary angiography should be reserved for patients whose estimated mortality from vascular surgery is substantially higher than average. PMID- 7783302 TI - Serum total cholesterol and mortality. Confounding factors and risk modification in Japanese-American men. AB - OBJECTIVE: To further investigate the relationship between serum total cholesterol (TC) level and mortality due to major causes. In particular, is the elevated mortality among persons with low TC levels due to confounding conditions that both lower TC level and increase the risk of mortality, and is the association between low or high TC level and mortality homogeneous in the population or, alternatively, restricted to persons with other risk factors? STUDY DESIGN: Prospective cohort study. SETTING: Free-living population in Oahu, Hawaii. PARTICIPANTS: A total of 7049 middle-aged men of Japanese ancestry. MAIN OUTCOME MEASURES: Age- and risk factor-adjusted mortality due to coronary heart disease, hemorrhagic stroke, cancer, chronic obstructive pulmonary disease, nonmalignant liver disease, trauma, miscellaneous and unknown, and all causes. RESULTS: During 23 years of follow-up, a total of 1954 deaths were documented (38% cancer, 25% cardiovascular, and 37% other). Men with low serum TC levels (< 4.66 mmol/L [< 180 mg/dL]) were found to have several adverse health characteristics, including a higher prevalence of current smoking, heavy drinking, and certain gastrointestinal conditions. In an age-adjusted model, and in relation to the reference group (4.66 to 6.19 mmol/L [180 to 239 mg/dL]), those in the lowest TC group (< 4.66 mmol/L [< 180 mg/dL]) were at significantly higher risk of mortality due to hemorrhagic stroke (relative risk [RR], 2.41; 95% confidence interval [Cl], 1.45 to 4.00), cancer (RR, 1.41; 95% Cl, 1.17 to 1.69), and all causes (RR, 1.23; 95% Cl, 1.09 to 1.38). Adjustment for confounders in multivariate analysis (and exclusion of cases with prevalent disease at baseline and deaths through year 5) did not explain the risk of fatal hemorrhagic stroke but reduced the excess risk of cancer mortality by 51% (to 1.20 from 1.41) and reduced the excess risk of all-cause mortality by 56% (to 1.10 from 1.32) in the low TC group. In addition, there were clear differences in the patterns of risk when comparing men with and without selected risk factors (ie, smoking, alcohol consumption, and untreated hypertension). CONCLUSIONS: We conclude that the excess mortality at low TC levels can be partially explained by confounding with other determinants of death and by preexisting disease at baseline, and TC mortality associations are not homogeneous in the population. In our study, TC level was not associated with increased cancer or all-cause mortality in the absence of smoking, high alcohol consumption, and hypertension. PMID- 7783303 TI - T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. AB - OBJECTIVE: To test the hypothesis that peripheral blood mononuclear cells in women with unexplained recurrent abortion (URA) produce T-helper 1 (TH1)-type cytokines in response to trophoblast antigens. DESIGN: Cohort study. SETTING: Medical center. PARTICIPANTS: A total of 244 women with URA, 13 reproductively normal parous control women, and 10 men. MAIN OUTCOME MEASURES: Supernatants from trophoblast-activated peripheral blood mononuclear cells from all participants were tested for toxic effects on mouse embryos and by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-gamma). Supernatants from 20 URA patients with embryotoxic activity and IFN-gamma, 13 reproductively normal parous women, and 10 men were further tested by ELISA for other TH1-type cytokines (interleukin 2 [IL-2], tumor necrosis factor-beta [TNF-beta]), TH2-type cytokines (IL-4, IL 10), and TNF-alpha. RESULTS: Embryotoxic activity was detected in supernatants from 160 of 244 URA patients and in none of the controls. Interferon gamma was detected in supernatants from 125 of 244 URA patients and was significantly associated with embryotoxicity (121 of 160 supernatants with embryotoxicity vs four of 84 supernatants without embryotoxicity [P < .001]). Of 20 supernatants from patients chosen for further study, all were positive for TNF-alpha, 17 for TNF-beta, two for IL-10, and one for IL-4. No cytokines were detected in supernatants from unstimulated or red blood cell membrane-activated cells of women with URA. In contrast, trophoblast-activated lymphocyte supernatants from reproductively normal women and men neither were embryotoxic nor contained TH1 type cytokines, but most contained the TH2-type cytokine IL-10. Three supernatants from reproductively normal women also contained IL-4. CONCLUSION: Whereas TH1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, TH2-type immunity may be a natural response to trophoblast contributing to successful pregnancy. PMID- 7783304 TI - The independent practice association in theory and practice. Lessons from experience. AB - This article examines an advanced managed care area, the San Francisco East Bay Area in California, for basic organizational issues posed by managed care for the medical profession. Of the three basic structures found, the independent practice association (IPA) model is theoretically most promising. Unlike the integrated health plan, the IPA seeks to retain traditional practice autonomy. Unlike the isolating direct gatekeeper model, the IPA assembles physicians in self-directed groups to invent and implement solutions and to exert political influence upward. In practice, however, it has proved difficult to balance practice autonomy with IPA authority. Both large, successful East Bay Area IPAs show signs (perhaps inevitably) of favoring authority over autonomy, as shown by their policies on governance, membership, and administration. Several policies are suggested to help redress this balance. Medical leaders must act now, before all the evidence is in, or the institutions of the past--hospitals and insurance companies--will control our future. PMID- 7783305 TI - Automated telephone screening survey for depression. AB - OBJECTIVE: To test the application of fully automated telephone screening using computerized digital voice recordings and touch-tone responses to assess symptoms of depression. DESIGN: A cross-sectional study of a 2-week-long telephone survey. SETTING: Toll-free telephone calls placed from home, work, or school to a central telephone/computer system at a telecommunications company in the Boston, Mass, area. PARTICIPANTS: A total of 1812 participants called the system. Of these, 278 were students and faculty at a large midwestern state university, 725 were employees of a large northeastern high-technology firm, and 809 did not identify which site they were calling from. MAIN OUTCOME MEASURES: The 20-question multiple-choice Zung Depression Scale was used to screen for depressive symptoms, and additional questions gathered demographic and caller satisfaction information. RESULTS: No technical problems were encountered during the trial. Of 1812 callers, 1597 (88.1%) completed all questions. Of these, 412 callers (25.8%) met criteria for "moderate or marked" depression and another 194 (12.1%) met criteria for "severe or extreme" depression. The majority of callers scoring positive for depression had received no previous treatment for depression. Of callers who completed the screening questionnaire, 74.6% reported the call to have been at least "moderately" helpful. CONCLUSION: Readily available low-cost technology provides a fully automated, widely accessible, and confidential method of screening for a common mental illness. PMID- 7783307 TI - NIH consensus conference: Total hip replacement. NIH Consensus Development Panel on Total Hip Replacement. AB - OBJECTIVE: To provide physicians with a current consensus on total hip replacement. PARTICIPANTS: A nonfederal, nonadvocate, 13-member consensus panel representing the fields of orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, internal medicine, public health, geriatrics, biostatistics, and a public representative. In addition, 27 experts in orthopedic surgery, rehabilitation and physical medicine, biomechanics and biomaterials, rheumatology, geriatrics, and epidemiology presented data to the consensus panel and a conference audience of 425. EVIDENCE: The literature was searched through MEDLINE and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS: The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. CONCLUSIONS: Total hip replacement is an option for nearly all patients with diseases of the hip that cause chronic discomfort and significant functional impairment. Most patients have an excellent prognosis for long-term improvement in symptoms and physical function. At this time, a cemented femoral component using modern cementing techniques, paired with a porous-coated acetabular component, can give excellent long-term results. Revision of a total hip replacement is indicated when mechanical failure occurs. Continued periodic follow-up is necessary to identify early evidence of impending failure so as to permit remedial action before a catastrophic event. PMID- 7783306 TI - Myocardial injury in critically ill patients. A frequently unrecognized complication. AB - OBJECTIVE: To determine the incidence and effect of unrecognized cardiac injury in critically ill patients. DESIGN: Prospective, blinded, single-center study. SETTING: The medical and respiratory intensive care unit of an academic health center. PATIENTS: Two hundred nine patients (224 admissions). MAIN OUTCOME MEASURES: Daily measurement of levels of cardiac troponin I, a sensitive, highly specific, and long-lived marker of myocardial injury. Concurrently, signs and symptoms potentially related to myocardial ischemia were tabulated by blinded investigators. All clinical evaluation and management decisions were made by the physicians responsible for the care of the patient. RESULTS: Thirty-two (15%) of the 209 patients had evidence of myocardial damage based on elevated levels of cardiac troponin I. Only 12 (37%) of these 32 patients were diagnosed as having acute myocardial infarction by the intensive care unit staff. Cardiac damage was unrecognized in the other 20 (63%). Unrecognized cardiac injury was more common in young patients and in blacks. Mortality in patients with myocardial injury that was recognized (42%) or unrecognized (40%) was higher than in those without myocardial injury (15%) (P < .001). Patients with cardiac injury were more frequently hypotensive (75% vs 50%; P = .007) and in need of mechanical ventilation (66% vs 27%; P < .001) and had longer intensive care unit stays (5.3 vs 3.1 days; P < .007) than patients without cardiac injury. CONCLUSION: The incidence of myocardial injury defined by elevated levels of cardiac troponin I was unexpectedly high and associated with increased morbidity and mortality. Clinically, it was often unrecognized. PMID- 7783308 TI - The adolescent viewpoint. Implications for access and prevention. PMID- 7783309 TI - Recurrent pregnancy loss and cytokines. Not as simple as it seems. PMID- 7783310 TI - Exercise and hypertension. PMID- 7783311 TI - A piece of my mind. Teen sex blues. PMID- 7783312 TI - [Tosufloxacin]. PMID- 7783313 TI - [A comparative study of tazobactam/piperacillin and piperacillin in bacterial pneumonia]. AB - The efficacy, safety and usefulness of tazobactam/piperacillin (TAZ/PIPC), in bacterial pneumonia and lung abscess were determined with PIPC as the control in a multi-institutional comparative study a penicillin antibiotic for injection prepared by combining a newly developed beta-lactamase inhibitor, tazobactam (TAZ), with a broad spectrum penicillin antibiotic, piperacillin (PIPC), at a ratio of 1:4. TAZ/PIPC was intravenously injected at a dose of 2.5 g (titer) twice a day, and PIPC at a dose of 2.0 g (titer) twice a day as a rule for 14 days. The following results were obtained: 1. The efficacy rates for bacterial pneumonia and lung abscess were 94% (80/85) in TAZ/PIPC group and 89% (70/79) in PIPC group, showing no significant difference between the two groups. 2. In a comparison of degrees of improvement in clinical symptoms, signs and laboratory findings, there were no significant differences between the two groups except for results on thoracic rales after three days of administration. 3. As for bacteriological effects, the elimination rates of causative organisms were 98% (40/41) in the TAZ/PIPC group and 80% (28/35) in the PIPC group. Thus, the TAZ/PIPC group was significantly superior to the PIPC group. The TAZ/PIPC group showed significantly better eradication of bacteria as well. Bacteria considered to be pyogenic were detected in 80 patients (43 administered TAZ/PIPC and 37 administered PIPC), but beta-lactamase production was confirmed in only 11 patients of each group. There were no significant differences in bacteriological effects among these patients. Minimum inhibitory concentrations of TAZ/PIPC against beta-lactamase producing organisms were distinctly superior to those of PIPC. 4. Side effects occurred in 10% (10/96) of the TAZ/PIPC group and 7% (7/95) of the PIPC group. Abnormal clinical laboratory test values were observed in 22% (20/92) of the TAZ/PIPC group and 18% (17/93) of the PIPC group. Thus, there were no significant differences between the two administration groups. 5. The usefulness rate in the TAZ/PIPC group was 87% (75/86) and it was 85% (67/79) in the PIPC group, showing no significant difference between them. The results suggest that TAZ/PIPC administered at a dose of 2.5 g (titer) twice a day is more useful than PIPC administered at a dose of 2.0 g (titer) twice a day in the treatment of bacterial pneumonia. PMID- 7783314 TI - [A comparative study of tazobactam/piperacillin and piperacillin in chronic respiratory tract infections]. AB - The efficacy, safety and usefulness were evaluated for a combined antibiotic tazobactam/piperacillin (TAZ/PIPC) consisting of a new beta-lactamase inhibitor, tazobactam (TAZ), and a broad spectrum penicillin antibiotic, piperacillin (PIPC), in chronic respiratory tract infections with PIPC as the control in a multi-institutional comparative study. The drugs used were a preparation containing 0.5 g of TAZ and 2.0 g of PIPC per vial (TAZ/PIPC group) and a preparation containing 2.0 g of (PIPC group). The drugs were intravenously injected one vial at a time twice a day for 14 days as a rule. The following results were obtained: 1. Clinical effect There was no significant difference between TAZ/PIPC (86% or 76/88) and PIPC (81% or 69/85). 2. Bacteriological effect There was no significant difference between TAZ/PIPC (93% or 42/45) and PIPC (88% or 36/41) in terms of bacterial eradication rates. In 34 patients with beta-lactamase-producing pyogenic bacteria, there was no significant difference between TAZ/PIPC (77% or 10/13) and PIPC (88% or 15/17). 3. Degrees of improvement in clinical symptoms, signs and laboratory findings The TAZ/PIPC group was likely to show reductions in fever and the amount of sputum soon after administration. 4. Side effects Incidences of side effects were 7% (7/96) in the TAZ/PIPC group and 3% (3/89) in the PIPC group, showing no significant difference between the two groups. The main symptoms were allergic reaction and gastrointestinal symptoms. 5. Abnormal clinical laboratory test values The incidence was 17% (15/89) in the TAZ/PIPC group and 21% (18/87) in the PIPC group. The main symptoms were eosinophilia and hepatic dysfunction, and most of these symptoms were mild. 6. Usefulness The usefulness rates in the TAZ/PIPC group were 80% (71/89) and 78% (66/85) in the PIPC group, showing no significant difference. Thus, TAZ/PIPC exhibited excellent clinical effects and presented no troubles with safety. When comprehensively evaluated, TAZ/PIPC appears to be a very useful drug for the treatment of chronic respiratory tract infections. PMID- 7783315 TI - [Clinical evaluation of cefpodoxime proxetil, a new oral cephem, in the treatment of respiratory tract infections with the special reference to community-acquired Streptococcus Pneumoniae infections]. AB - The clinical usefulness of cefpodoxime proxetil (CPDX-PR) was investigated in the treatment of pneumonia and chronic airway infections occurring in patients first visiting our outpatient clinic or those being treated at the outpatient clinic. CPDX-PR was orally administered twice a day after meals at a dose of 100-200 mg for acute respiratory tract infections and at a dose of 200 mg for chronic respiratory tract infections. Excellent, good, fair, and poor responses were observed in 20, 33, 10, and 3 of 66 patients (4 with acute bronchitis, 27 with pneumonia, and 35 with acute exacerbation of chronic airway infection), respectively, demonstrating an 80.3% efficacy rate (53/66). Causative organisms, including Streptococcus pneumoniae, were all eradicated from the patients whose causative organisms were examined over time, although 2 of the patients were superinfected with Pseudomonas aeruginosa. There were no serious adverse reactions or abnormal changes in laboratory test results. It was concluded that CPDX-PR could be used as a first-choice drug for the treatment of respiratory tract infections at an outpatient clinic, and that this drug should acquire greater importance in particular consideration of recent increases in infections with S. pneumoniae. PMID- 7783316 TI - [Antimicrobial activities of sulbactam/ampicillin against clinically isolated microbial strains]. AB - Antimicrobial activities were examined for sulbactam/ampicillin (SBT/ABPC) against clinically isolated microbial strains in 1987, 1990, 1994. Besides, the beta-lactamase productivity and MICs of these strains were measured, and the following conclusions were obtained. 1. The ratio of beta-lactamase producing strains were 90% of methicillin (DMPPC)-susceptible Staphylococcus aureus subsp. aureus (MSSA), about 80% of DMPPC-resistant S. aureus (MRSA), 100% of Escherichia coli, Klebsiella pneumoniae subsp. pneumoniae and Proteus mirabilis, 95% of Moraxella subgenus Branhamella catarrhalis and 15-20% of Haemophilus influenzae. Several kinds of beta-lactamase productivity were observed. 2. Antimicrobial activities of SBT/ABPC against beta-lactamase producing strains of MSSA, M. (B.) catarrhalis, H. influenzae, and almost all of Enterobacteriaceae were stronger than those of ampicillin (ABPC) and piperacillin (PIPC), but antimicrobial activities of SBT/ABPC were weak against MRSA and cephems (CEPs)-resistant strains detected in some of Enterobacteriaceae. 3. It appeared that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) or PCG resistant S. pneumoniae (PRSP) and CEPs-resistant Escherichia coli increased year by year. 4. Antimicrobial activities of SBT/ABPC were strong against Streptococcus pyogenes, S. pneumoniae, M. (B.) catarrhalis and H. influenzae including beta-lactamase producing strains. Additionally, beta-lactamase inhibiting effect of SBT was observed against beta-lactamase produced by S. aureus and K. pneumoniae which demonstrate indirect pathogenicity. Thus, SBT/ABPC is an injectable antibiotic that is expected to demonstrate clinical usefulness, especially as the first line drug for the respiratory tract infections that are community-acquired. PMID- 7783318 TI - Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin, cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus. I. Effect of NaCl. AB - The in vitro antimicrobial activity of cephamycin, e.g. cefmetazole and cephalosporin, such as cefazolin, cefotiam, cefamandole and cefoperazone, alone and in combination, was studied employing 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 30 strains of methicillin-resistant Staphylococcus aureus (MRSA). Using the checkerboard agar dilution method, strong synergism was demonstrable in a majority of MSSA and MRSA strains for cefmetazole combined with these cephalosporins, with the minimum fractional inhibitory concentration index < or = 0.5. In the presence of a concentration < or = 6.25 micrograms/ml of these cephalosporins in Mueller-Hinton agar medium, the activity of cefmetazole against MRSA was most prominently potentiated by cefotiam, followed by cefamandole, cefazolin and cefoperazone. At a concentration of 12.5 micrograms/ml, cefotiam and cefamandole showed a similar effect in potentiation of cefmetazole activity. In hypertonic agar medium containing 4% NaCl, these synergistic combination effects were reduced. However, the activity of cefmetazole and cefamandole in combination under these conditions was influenced to a lesser extent and more potent than that of other combinations. PMID- 7783317 TI - [Postantibiotic effects (PAE's) of macrolide antibiotics evaluated using Bioscreen C method]. AB - Postantibiotic effects (PAE's) of macrolide antibiotics were determined for Staphylococcus aureus and Enterococcus faecalis using viable counting and Bioscreen C method and the two methods were compared. No major differences between the two methods were observed. The Bioscreen C method was less laborious than the viable counting. The durations of PAE for S. aureus following exposures to erythromycin (EM), josamycin (JM) and rokitamycin (RKM) for 2 hours at twice the MICs were in ranges of 0.85 to 1.45, 2.36 to 3.48 and 1.93 to 5.45 hours, respectively. A definite PAE of 1.0 to 5.8 hours was also observed in E. faecalis strains exposed for 2 hours to EM, JM and RKM at twice the MICs. PMID- 7783320 TI - [Antimicrobial activities of piperacillin against fresh clinically isolated strains]. AB - In order to evaluate the antimicrobial activity of piperacillin (PIPC), along with control agents, minimum inhibitory concentrations (MIC's) were determined against fresh clinically isolated strains from January to June, 1994. 1. The MIC70's of PIPC against major strains were approximately equal to those reported in the mid 1980s. 2. Strains for the study were supplied in approximately equal numbers from community-acquired hospitals and general hospitals. The ratios of bacteria resistant to beta-lactams including PIPC were low in the former group and high in the latter. 3. "New types of beta-lactam-resistant strains" which did not exist in mid 1980s but found at this time included benzylpenicillin (PCG) insensitive Streptococcus pneumoniae, PCG-resistant S. pneumoniae, cephems resistant Escherichia coli and beta-lactamase producing Prevotella spp. These bacteria were also found among strains obtained from community-acquired hospitals. PMID- 7783319 TI - Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam, cefamandole or cefoperazone in combination against methicillin sensitive and -resistant Staphylococcus aureus. II. Effect of inoculum size. AB - The inoculum effect was studied on the activity of cefmetazole and cefotiam, cefamandole or cefoperazone alone and in combination against 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 20 strains of methicillin resistant Staphylococcus aureus (MRSA) by means of the checkerboard titration method with Mueller-Hinton agar plate using 10(6) and 10(8) CFU/ml. The antimicrobial activity against MSSA and MRSA was potentiated synergistically in combination of cefmetazole and these cephalosporins either with inoculum size 10(6) or 10(8) CFU/ml. At a concentration of cephalosporins < or = 6.25 micrograms/ml, the combination effect of cefmetazole and cefotiam or cefamandole against MRSA was more potent than that of cefmetazole and cefoperazone. With a higher inoculum size the effect was reduced. Under these conditions with a low dose level of drugs, the enhancement of the activity of cefmetazole by cefotiam was least influenced by inoculum size among cephalosporins studied. PMID- 7783321 TI - [Clinical study of ciclosporin in patients with aplastic anemia and pure red-cell aplasia]. AB - We administered cyclosporine to patients with aplastic anemia and pure red-cell aplasia as a multicenter clinical trial. The cyclosporine was given by a dose of 6 mg/kg orally daily for 16 weeks. The efficacy of cyclosporin for aplastic anemia was 13.8% after 8 weeks, and 28.0% after 16 weeks. The severity of the disease was improved, and the amount of blood transfusion was reduced. The efficacy of cyclosporine for patients with pure red-cell aplasia was 60.0% at 16 weeks treatment. Adverse effects of cyclosporine were observed in some patients and the hirsutism was seen most commonly. In laboratory data, an increase of serum creatinine was seen but was transient. Our results showed that cyclosporine is an effective drug for treatment of aplastic anemia and pure red-cell aplasia. PMID- 7783322 TI - [A case of Kasabach-Merrit syndrome complicated with DIC treated effectively by long term oral administration of warfarin]. AB - A 20 year-old female patient with Kasabach-Merrit syndrome, suffered from chronic consumption coagulopathy due to localized intravascular coagulation in the tumors. She had been diagnosed as Kasabach-Merrit syndrome immediately after birth and below knee amputation of her right lower leg was performed at the age of 2 years because of her giant hemangioma on the right foot and lower leg. After the operation, she had often complained of severe pain and enlargement of the residual tumors due to continuous thrombus formation within the tumors. She was admitted to the third Department of Tohoku University Hospital in order to initiate oral anticoagulant therapy with Warfarin at the age of 12 years. After the administration of 2.5 mg/day Warfarin, she has maintained good clinical condition until now, despite the occasional occurrence of coagulation abnormalities. We believe that the results of this case indicate the efficacy of oral anticoagulant therapy in the treatment of chronic consumption coagulopathies complicated with other diseases. PMID- 7783323 TI - [Aspergillus lumbar discitis in a patient with acute lymphoblastic leukemia following induction therapy]. AB - A 47-year-old female was admitted in October 1988 because of anemia and lymphoblastic cells in peripheral blood. A bone marrow aspirate was hypercellular with 93.9% lymphoblasts negative for peroxidase staining. The case was diagnosed as ALL (L2), and treated with JALSG ALL-87 regimen. She developed spiky fever and endotoxin shock due to bacteremia caused by pseudomonas aeruginosa, then was treated with several antibiotics. With the recovery of leukocytes, the chest X ray showed an infiltrative shadow and a cavity forming lung abscess resembling aspergilloma in her left lung. The cavity improved of transbronchial infusion following amphotericin B (AMPH-B). Although she achieved complete remission, she felt severe lumbago accompanied by a marked erosion of the vertebral body with disc space narrowing on her X-ray. Then she underwent surgery to remove a disc abscess, and 1 colony of the aspergillus species was cultured from the specimen. She was treated with intravenous AMPH-B, and post remission therapies were performed under the injection of anti-fungal agents. No remarkable symptoms of complications were recognized during the chemotherapy. AMPH-B is useful and safe for the management of aspergillus discitis. PMID- 7783324 TI - [Persistent discrepancy between FDP and D-dimer in a patient with acute leukemia]. AB - In a patient with acute myeloblastic leukemia, serum fibrinogen/fibrin degradation products (FDP) were markedly elevated to 54.91 micrograms/ml, but plasma D-dimer was only slightly elevated (1.44 micrograms/ml). FDP in plasma measured by a method using monoclonal antibody specific to FDP was less than 5 micrograms/ml. Gradual reduction of blastic cells was obtained with the therapy of low-dose cytarabine, G-CSF and etoposide. The serum FDP increased up to 71.74 micrograms/ml accompanied with a transient elevation of D-dimer, and subsequently declined without any anticoagulant therapy. However, a discrepancy between serum FDP and plasma D-dimer lasted for a long time. In this case persistent acceleration of coagulation and fibrinolysis which may result in the elevation of serum FDP was not observed, suggesting that the greater part of increased FDP didn't reflect the true FDP formed by plasmin. There were possibilities that elevated serum FDP values were also caused by the presence of soluble fibrin, unclottable fibrinogen and the degradation products by nonplasmic proteinases. Simultaneous measurements of FDP and D-dimer are useful for a more accurate evaluation of hyperfibrinolytic states and to avoid possible misinterpretations due to falsely positive FDP. PMID- 7783325 TI - [Chronic active EB virus infection accompanied by monoclonal proliferation of granular lymphocytes]. AB - An 18-year-old man was admitted to our hospital because of 39 degrees C fever for over one month, marked hepatosplenomegaly, and pancytopenia. Malignant histiocytosis, malignant lymphoma, or hemophagocytic syndrome were ruled out by bone marrow aspiration and liver biopsy. A diagnosis of chronic EB virus infection was made according to his characteristic clinical features, abnormally high titiers of anti-EBV antibodies (VCA-IgG x 2560, EA-IgG x 1280), and the detection of EBV genome in the peripheral blood mononuclear cells by polymerase chain reaction. He also manifested granular lymphocyte proliferative disorder (GLPD). The phenotype of the proliferating granular lymphocytes was CD2 (+), CD3 (-), CD56 (+), and IL-2R beta (+), showing the NK lineage of these cells. Chromosomal abnormality of the cells cultured for a short time with IL-2 and a monoclonal junctional DNA structure of EB virus terminal repeat analyzed by the Southern blotting provided definitive evidence for the monoclonal expansion of the granular lymphocytes. These findings indicate a causative role of EV virus in NK-GLPD or NK-leukemia. PMID- 7783326 TI - [Neoplastic angioendotheliosis diagnosed by open lung biopsy]. AB - Neoplastic angioendotheliosis (NAE) is a rare neoplastic disease, and its pre mortem diagnosis is extremely difficult. A 49-year-old male developed vertigo, hearing and visual disturbance, transverse myelopathy below Th 5 and hypercalcemia. These symptoms were markedly improved by VEPA chemotherapy. Thirty four months after onset, diffuse reticular shadows were noted on chest X-ray. The biopsy specimen of the lung revealed intravascular lymphoid cells differentially stained with L26 and LCA. Southern blot analysis of the DNA from the tissue showed rearranged bands for the immunoglobulin gene (JH). A diagnosis of NAE of B cell nature was established. PMID- 7783327 TI - [Plasma tissue factor assay: its significance and application]. PMID- 7783328 TI - [Reticulated platelets--automated measurement and clinical utility]. AB - Development of the method to determine reticulated platelets is briefly reviewed. A new rapid method to automatically count reticulated platelets is very recently established by our research group. The principle of the measurement of reticulated platelets is based on flow cytometry. The platelets are quickly stained with a RNA fluorescent dye, auramine O and fluorescent intensity (RNA content) and forward scatter (cell size) are measured in only 80 seconds with a reticulocyte counter, equipped with special software for analysis of reticulated platelets. Both of the reproducibility and the linearity were shown to be good. Normal percentage value for reticulated platelets was 0.98% +/- 0.41% and its absolute count was 2.12 +/- 0.69 x 10(9)/l. The absolute count was decreased in patients with reduced thrombopoiesis such as acute myeloblastic leukemia, aplastic anemia and was elevated in patients with essential thrombocythemia and in chronic myelocytic leukemia. The patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. An apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia in a couple of leukemic patients. These suggest that an automated measurement of reticulated platelets can be clinically useful to estimate thrombopoiesis in bone marrow. PMID- 7783329 TI - [Clonal study of hematopoietic cells]. AB - Clonal analyses using X-chromosome inactivation patterns of the phosphoglycerate kinase (PGK) and DXS255 (M27 beta) genes were performed in women with various hematological diseases or normal hematopoiesis. Four (17%) of 24 hematologically normal females had a skewed Lyonization pattern. It, however, appeared that in the majority of cases clonality determination of myeloid cells would be possible in comparison with lymphocytes. Blasts of acute myeloid leukemia (AML) (21) and granulocytes and bone marrow cells of chronic myeloproliferative disorders (6) were all shown to be clonal, suggesting that this method was useful for the concept formation of a clonal disorder. Twelve of 14 patients with the myelodysplastic syndromes had a clonal pattern and 8 of 10 patients with aplastic anemia had a polyclonal pattern. Three of 34 patients with AML during remission were diagnosed as a clonal hematopoiesis and associated with features of myelodysplasia during remission, when clonal patterns are different in patients with the same disease, it seems important to elucidate their clinical implications. PMID- 7783330 TI - [Cytofluorometric analysis of tumor cell size and follicle formation of B-cell lymphomas]. AB - In order to investigate the size variation of neoplastic B cells (NBC) from lymph nodes of patients with B-cell lymphomas (BCL), we carried out two-dimensional analysis by flow cytometry (FCM) using the forward light scatter (FLS) and the fluorescence intensity (FI) of surface immunoglobulin light chain (sIgL). NBC were identified as having the homogeneous characteristics of both FLS and tumor restricted sIgL (kappa or lambda). The FLS variation of NBC was then analyzed using CD3+ T-cells as a scale control. The results closely coincided with the cell types determined by the pathologic diagnosis. Secondly, we used FCM to investigate how strongly NBC express VLA-4 alpha and LFA-1 alpha, which seemed to play important roles in neoplastic follicle formation. The expression intensities of these molecules were classified into three grades (-, + & ++). The results were presented in the order of VLA-4 alpha and LFA-1 alpha; follicular 8/15 (++/++), 6/15 (++/+), 1/15 (+/++), partially follicular 3/5 (+/++), 2/5 (+/+), diffuse 2/16 (++/-), 6/16 (+/++), 8/16 (+/+), B-CLL 8/8 (-/+ or -). These findings suggest that follicular lymphomas are phenotypically distinguishable from diffuse lymphomas. PMID- 7783331 TI - [Soluble lymphocyte antigens in hematological diseases]. AB - Plasma levels of soluble CD8 (sCD8) and soluble CD4 (sCD4) in patients with infectious mononucleosis (IM) and hematological disorders were studied. In IM patients, a marked increase in sCD8 (22, 366 +/- 2,702U/ml, control: 219 +/- 10U/ml, p < 0.0001) and significant increase in sCD4 (19.3 +/- 0.9, control: 8.1 +/- 0.2, p < 0.0001) strongly suggest activation of both CD8+ and CD4+ lymphocytes, which is important in restraining Epstein-Barr virus-infected B lymphocytes. We showed that the elevation of plasma sCD8 is due to expansion of CD8+ subset as well as increased sCD8 release from each CD8+ cell. Increased sCD4 release from CD4+ lymphocytes was also seen. During convalescence sCD8 and sCD4 levels showed progressive decrease; however, even at 60-120 days after onset the levels of sCD8 and sCD4 remained higher than normal, suggesting prolonged lymphocyte activation. In hematological malignancies, elevated serum levels of sCD4 and sCD8 were found in non-Hodgkin lymphoma (NHL), acute lymphocytic leukemia, multiple myeloma, acute non-lymphocytic leukemia and chronic myelogenous leukemia. Levels of sCD4 and sCD8 in patients with NHL reflect disease status and are useful in monitoring disease activity. PMID- 7783332 TI - [Detection of minimal residual disease by means of FISH and PCR methods and its clinical evaluation]. AB - The monitoring of MRD by FISH and PCR is now clinically evaluated for a prediction of the relapse of leukemia. However, these methods include several technical limitations. In FISH, an appropriate cut off value should be settled for each probe or procedure in estimating chromosomal gain, loss, or translocation and the sensitivity depends on the cut off values but it may reach to 10(-3). In PCR, the sensitivity is higher than that of FISH especially using genomic DNA as a template. However, the detection of chromosomal translocation specific DNA or RNA constructs is currently applicable to limited cases and the amplification of Ig or TCR gene rearrangement has a major pitfall caused by the clonal evolution. Clinically, MRD can be an indicator for a prediction of the relapse. For example, a greater MRD on entering CR tends to be related with an early relapse, a return to MRD-positive after disappearance of MRD will be a sign of impending relapse, and MRD negativity at the termination of therapy may be correlated with a long-term disease free status. More precise evaluation of MRD is necessary with regard to therapeutic strategy. PMID- 7783333 TI - [Molecular biological analysis of hereditary thrombophilia--genetic characterization of protein S deficiency]. AB - Protein S is a plasma glycoprotein, which functions as a cofactor for activated protein C in the protein C pathway and also directly inhibits factors Va and Xa, independently of protein C. In plasma, protein S circulates as a free molecule (40%) or in a complex with C4b-binding protein (60%). Only a free protein S acts as an anticoagulant and its activity is lost by binding to C4b-binding protein. The physiological importance of protein S has been established by observations in patients with hereditary protein S deficiency who have an increased risk of developing thrombosis. Several previous studies reported that hereditary protein S deficiency was as common as protein C deficiency and that approximately 5% of hereditary thrombophilia was caused by protein S deficiency. But molecular biological analysis of protein S deficiency is not as advanced as protein C deficiency because the genetic characterization of protein S deficiency is limited by the presence of the inactive pseudogene that is highly homologous to the active true gene. Only a few previous studies have examined the genetic features of hereditary protein S deficiency. Further investigation is needed to characterize the pathophysiology and molecular basis of hereditary protein S deficiency. PMID- 7783334 TI - [Study of signal transduction through thrombin receptor and anti-thrombotic strategy using its controls]. AB - Thrombin, a key enzyme in the hemostatic pathway, also has various effects on the function of human platelet, endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC). A thrombin receptor (TR) has been cloned and is thought to mediate a variety of thrombin-induced responses. 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. TR stimulation resulted in a biphasic activation of NF-kappa B and the late phase of which required new NF-kappa B synthesis. We showed that the antisense oligodeoxynucleotides (ODNs) of NF-kappa B have a marked inhibitory effect on thrombin-induced cellular responses. Furthermore, E5510, a compound with anti platelet activity preferentially inhibited the thrombin-inducible NF-kappa B activation. Therapeutic potential of inhibition of TR-NF-kappa B activation signaling for treatment with thrombotic disease is also indicated. PMID- 7783335 TI - [Monitoring for oral anticoagulant therapy]. AB - Warfarin has been widely used for an oral anticoagulant therapy against thrombotic diseases. For the monitoring of its anticoagulant intensities, prothrombin time (PT) ratio and percentage of thrombotest (TT) are commonly used in Japan. Recently, International Normalized Ratio (INR) was recommended by ICSH/ICTH. Practicality and usefulness of INR and its combined use of thrombin antithrombin III complex (TAT) for the monitoring of oral anticoagulation therapy were evaluated among patients of ischemic heart disease with or without interventions, and of cardiomyopathies and valvular diseases. Difference in thromboplastin sensitivities have been shown to cause errors in PT elongation and in the evaluation of anticoagulant activity, so that the monitoring only by PT ratio is considered to be irrelevant, and that INR is recommended to be used. INR was comparable to the levels of TT. Majority of the patients, whose TAT levels were kept normal, were controlled below the proposed therapeutic ranges of INR. With the combination of INR and TAT monitoring, anticoagulant effect of warfarin could be achieved safer in lower dose than the levels that might cause bleeding accidents. PMID- 7783336 TI - [Classification and treatment of DIC]. AB - Disseminated intravascular coagulation (DIC) is characterized by extreme activation of intravascular coagulation, and clinical manifestations such as bleeding and/or multiple organ failure is sometimes observed in advanced cases of DIC. The balance of coagulation and fibrinolysis activation varies according to the underlying diseases of DIC. DIC cases are classified as the type with predominant coagulation activation and the type with predominant fibrinolysis activation in former type plasma levels of thrombin-antithrombin III complex (TAT) are greatly increased, and those of plasmin-alpha 2 plasmin inhibitor complex (PIC) are slightly increased. In addition plasma levels of plasminogen activator inhibitor 1 (PA1) are greatly increased, multiple organ failure is a major clinical manifestation in advanced cases and sepsis is a representative underlying disease. In the second type both plasma levels of TAT and PIC are greatly increased, plasma levels of PA1 are almost within normal limits. Bleeding is a major clinical manifestation in advanced cases and acute promyelocytic leukemia (APL) is a representative underlying disease. The classification of DIC should be considered when choosing treatment with DIC. Diagnosis of pre-DIC status is based on gradually decreasing platelets counts in sepsis and on mild elevation of FDP and D dimer in APL, leukemia and cancer. PMID- 7783337 TI - [Thrombosis in patients with SLE and antiphospholipid syndrome]. AB - Clinical and serological features in SLE patients with arterial or venous thrombosis were studied. The subjects consisted of 140 patients with SLE who met the revised criteria for the classification of SLE by the American Rheumatism Association. Forty patients (29%) had arterial or venous thrombosis. Arterial thrombosis such as stroke was found in 30 patients, and venous thrombosis such as deep vein thrombosis was seen in 24 patients. Average age at the disease onset was 34.5 +/- 12.5 years old. Renal disorder was found as a clinical feature, and IgG anticardiolipin antibodies (aCL), IgG phospholipid-dependent anti-beta 2 glycoprotein I (beta 2-GPI) antibodies and IgG anti-Annexin V antibodies were identified as serological features in SLE patients with thrombosis. These patients were diagnosed as having antiphospholipid syndrome. It was necessary to perform primary prevention therapy as well as secondary prevention therapy. Multiple thrombotic events in the past history and sustained positive reactions of IgG aCL were suggested as predictors of recurrent thrombosis. These data indicated the clinical and serological characteristics in SLE patients with arterial or venous thrombosis. PMID- 7783338 TI - [Treatment results of acute nonlymphocytic leukemia in childhood--Kyushu Yamaguchi Children's Cancer Study Group]. AB - Seventy-three children with acute nonlymphocytic leukemia (ANLL) have been treated with ANLL-85 and ANLL-88 protocol at Kyushu-Yamaguchi Children's Cancer Study Group between June, 1985 and February, 1993. Ten boys and 10 girls (0y4m 16ylm) were treated with the ANLL-85 protocol. The complete remission (CR) rate was 75% and the 5-year event free survival (EFS) was 20 +/- 9%. It was terminated because of frequent early relapse (within 6 months after CR). Thirty-four boys and 19 girls (0y3m-17ylm) were treated with the ANLL-88 protocol. The CR rate was 85% and the 5-year EFS was 32 +/- 7%. Early relapse rate with ANLL-88 was lower than that of ANLL-85, however 9 cases relapsed after terminating therapy. Although bone marrow transplantation (BMT) from related donors during the first CR was effective in ANLL-88, EFS was not improved. Recognition of risk factors and appropriate chemotherapy regimens with or without the support of stem cell transplantation may be necessary to cure children with ANLL. PMID- 7783340 TI - [Transformation into chronic myelomonocytic leukemia in a patient with primary myelofibrosis associated with severe hypoplasia: report of an autopsy case]. AB - A 70-year-old male was admitted because of anemia in September 1989, and primary myelofibrosis was diagnosed based on the presence of leukoerythroblastosis, a normal chromosomal analysis and pathological findings of fibrosis in bone marrow. Although he was anemic, he did not require any treatment for two years. Then his hematological status deteriorated to severe pancytopenia, and the marrow biopsy revealed marked hypoplasia with fatty replacement and scattered fibrosis. He was treated with metenolon without success and frequent transfusion of packed red cell was required. This hypoplastic status continued for seven months. In May 1992 his WBC count increased gradually with monocytosis. The marrow was filled with various stages of monocytes, with almost no fibrosis remaining. The chromosomal analysis was repeated but disclosed no abnormalities, consistent with the negative result of BCR-ABL rearrangement investigated by the RT-PCR method. One month later, when the patient died of multiple cerebral bleeding and infection, the leukocyte count exceed 90,000/microliters. It is known that major causes of death for patients with primary myelofibrosis are infection, bleeding, cardiac trouble and transformation to leukemia. We describe a case of myelofibrosis who developed to chronic myelomonocytic leukemia following severe aplastic phase. PMID- 7783339 TI - [Autoimmune hemolytic anemia reactivated by alpha-interferon therapy in a case of chronic active C-type hepatitis]. AB - A case with autoimmune hemolytic anemia (AIHA) induced by interferon-alpha (IFN alpha) is presented. A 40-year-old male who had a previous history of autoimmune hemolytic anemia, agranulocytosis and thrombocytopenia was admitted to our hospital because of chronic C type hepatitis. Liver biopsy was performed, which diagnosed chronic active hepatitis and IFN-alpha was administrated at a dose of 3 Meg unit per day. 11 days after the initiation of the therapy he developed hemolytic anemia, but Coombs tests were negative. Although IFN was withdrawn 15 days later, anemia became progressively more serious. 20 days later, both direct and indirect Coombs tests became positive. He was diagnosed as AIHA and treated with methylprednisolone pulse therapy, then he recovered soon afterward. Further analysis of Coombs tests revealed that he had both cold type and warm type (IgG) autoantibodies which was the same type of antibodies for AIHA he suffered 10 years ago. In conclusion, latent AIHA may be reactivated by the treatment with IFN-alpha. PMID- 7783342 TI - [Isolation and characterization of the hematopoietic stem cell]. AB - When one hundred of c-Kit+Sca-1+Lin- cells obtained from B6. Ly 5.1 mouse were injected into lethally irradiated B6. Ly 5.2, 100% of the mice injected survived. Sequential analyses of recipient's peripheral blood leukocytes revealed presence of Ly 5.1+ myeloid and lymphoid cells even 12 months after the injection. We also examined the fate of these cells in the recipient mouse after transplantation. Time course analyses of the mouse injected with 500 FACS-purified c-Kit+Sca-1+L- cells revealed that spleen is the primary site for expansion of the injected c Kit+Sca-1+Lin- cells. By day 28 s/p transplantation, more than 50,000 donor type c-Kit+Sca-1+Lin- cells were found in the spleen and over 15,000 cells in the bone marrow. By day 60, number of c-Kit+Sca-1+Lin- cells decreased in the spleen and returned to normal level in the bone marrow. Stem cell activity of the donor derived c-Kit+Sca-1+Lin- cells in the primary recipient was confirmed by in vitro and in vivo colony formation as well as transplantation to the secondary recipient. These results provide evidence that c-Kit+Sca-1+Lin- cells in the bone marrow have capability of self-renew as well as multilineage differentiation potential and that spleen is the primary site of stem cell expansion after bone marrow transplantation in mouse. PMID- 7783341 TI - [Recent progress in the treatment of adult acute leukemia]. AB - Due to the advance of chemotherapy and bone marrow transplantation, adult acute leukemia has become a curable disease. In acute myeloid leukemia, the JALSG AML89 study resulted in 77% complete remission (CR) rate in 326 adults and 38% 4.5-year disease-free survival (DFS) in CR cases. However, the result of acute lymphoblastic leukemia in the JALSG ALL87 study is not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS. For acute promyelocytic leukemia (APL), all trans retinoic acid works remarkably, and the JALSG AML92 study for newly diagnosed APL resulted in 89% CR in 109 adults and 81% 2.5-year DFS. PMID- 7783343 TI - [Macrophage cell cycle control by M-CSF/CSF-1]. AB - Temporally orderly activation of the cyclin-dependent kinases (cdks) governs the progression and the transitions of the cell cycle in mammalian cells. Macrophages require a specific growth factor, M-CSF/CSF-1, for their proliferation throughout the G1 phase of the cell cycle. Once cells enter S phase, macrophages complete mitosis in the absence of M-CSF/CSF-1. During the G1 phase, cyclin D1 is induced by M-CSF/CSF-1 stimulation and forms enzymatically active complex with cdk 4. The enzymatic activity of the cyclin D1 and cdk 4 complex could be negatively regulated by recently reported inhibitory proteins to determine the timing for entry into S phase in macrophages. PMID- 7783344 TI - [Prospects for antisense therapy]. AB - Inability to distinguish between normal and diseased cells by chemotherapeutic agents causes systemic toxic effects. This problem may be solved by the direct genetic approach using antisense oligodeoxynucleotide (AS ODN) based on the specificity of Watson-Crick base pair formation, if an appropriate disease specific target can be identified. Since the pioneering works by Zamecnik and Stephenson to inhibit gene expression using AS ODN, recent progress in cloning of pathogenic genes and technical advance in the synthesis of ODN analogues have spurred a research effort dedicated to the development of AS therapy for cancer and viral disease. Chemically-modified ODNs such as phosphorothioate analogues, which are nuclease resistant and considered to be suitable for clinical use, can effectively inhibit the expression of activated oncogenes or the viral replication and lead to the growth suppression of cancer cells and viral genomes in vitro and in experiments using animal models as well. Phase I clinical trials, designed to evaluate the toxicity of these compounds in leukemia or AIDS patients, have already commenced. In these trials, which are now in its infancy, a considerable number of problems will be encountered. However, these hurdles may not be insurmountable. PMID- 7783345 TI - [Current status and the future of HIV infection]. PMID- 7783346 TI - [HIV infection: pathophysiology and its clinical features--clinical course and surrogate marker]. AB - Clinical courses and several hematological and serological markers were evaluated in 34 patients with HIV infection (32 with hemophilia and 2 with homosexuality) who had been followed up at Shizuoka Prefecture Children's Hospital for 3 to 13 years, with the reference to the results observed in 1,082 patients with HIV infection registered with the Ministry of Health and Welfare Study Group, Natural History Committee. The results indicated as significant follow-up markers as (1) CD4- and CD8-positive lymphocyte count, (2) IgA, IgG and beta-2 microglobulin, (3) HIV p24 antigen and HIV culture isolation, and (4) serum HIV-RNA. Of these markers, the quantification of serum HIV-RNA seemed particularly useful for prognosis estimation, determination of therapy onset, and efficacy assessment of a given anti-HIV agent. In addition, we encountered 2 HIV-infected patients who seemed to meet the definition of long-term survivors. Factor analysis in these patients will be an important subject of investigation from a clinical point of view as well. PMID- 7783348 TI - [AIDS-associated lymphomas]. PMID- 7783347 TI - [Induction of protective immune responses by a chimeric soluble protein from a recombinant BCG vector candidate vaccine to HIV-1]. AB - We have been isolated HIV strains from blood specimens of HIV infected individuals in Japan for these 6 years. The number of specimens tested reached approximately 1,700 that ninety percent of them were from hemophiliacs repeatedly injected blood products from the United States. More than 300 of field HIV were successfully isolated from the samples. The isolation rates has decreased to 30 percent in 1993 from 40 percent in 1992, suggesting that treatment with anti-HIV drugs such as AZT and/or ddI may be effective to HIV-infected individuals. Further, both of the viral and genomic sequences of HIV were classified to be clade B virus. The clinical isolates that expressed IHIGPGRAFY sequence at the center of the HIV-V3 domain were found to be neutralized by an anti-clade B-V3 monoclonal antibody, mu 5.5. By individual levels, when asymptomatic seropositives have progressed to disease-states, neutralization core motif of GPGR in approximately 6% of the viruses has changed to GPGG and hydrophilic amino acid changed to hydrophobic amino acid, correlating the loss of binding activity to PND-peptide of Japanese Consensus virus. Further, rapid progressors to HIV induced diseases showed decreased activity of the binding antibody. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein, and established the PND-peptide secretion system in BCG. The recombinant BCG inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide followed by passive transfer of the DTH by the systemic route.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783349 TI - [Chemotherapy and vaccine against HIV infection]. AB - Anti-HIV treatment is the major strategy against HIV infection and AIDS. Nucleoside reverse transcriptase inhibitors have been studied extensively, and some of them have been approved for clinical use. Efficacy of non-nucleoside reverse transcriptase inhibitors and HIV-protease inhibitors are also being confirmed. It became clear, however, that all of these agent, allow emergence of drug-resistant HIV mutants when used as monotherapy. Therefore, combination therapy or alternating therapy using these and other new agents may become the main mode of treatment in the future. Clinical trials for HIV vaccines are now being conducted in U.S.A. and other countries. In many of them, immunological responses were confirmed, although clinical benefit was not known yet. Vaccines which induce cellular immunity against broad spectrum of epitopes are desired to overcome viral mutations. Gene therapy is very attractive, and extensive studies are being conducted in many laboratories including ours. Methodology for early and correct diagnosis of opportunistic infections are now developing especially by using molecular technology. Steady improvement in the clinical management of opportunistic infections is achieved. PMID- 7783350 TI - [Present situation of health care setting for patients living with human immunodeficiency virus type-1 in medical institutions of Japan]. AB - We investigated the present health care situation in medical institutes of medical doctors who are the members of human immunodeficiency virus type-1 (HIV) research group headed by Prof. Yamada through mailing-questionnaire. It was revealed that there are many HIV-treatment-related problems in medical institutes, included a refusal to accept a newly-diagnosed HIV-infected patients or to conduct surgical treatment on them. Furthermore, it was also clarified that there are quite a many HIV-infected patients who were not informed their HIV status yet, thus causing secondary-HIV-infection to their sexual partners. From these results, urgent drastic measures to solve these problems are needed for the caring patients living with HIV. PMID- 7783351 TI - [Hypocellular acute leukemia]. AB - To establish diagnostic criteria for hypocellular acute leukemia (HL) 32 cases (mean age 67) with 40% or less bone marrow cellularity were analysed and compared with 40 cases of MDS, 27 cases of AML in the elderly (60 > or = ) and 39 cases of AML in the young (60 <). The mean bone marrow cellularity was 30% in HL, 85% in MDS, 87% in elderly AML and 95% in young AML, respectively. Thus hypocellularity was evident in HL. Blast % in bone marrow of HL patients was 17-70% in all nucleated cells including lymphocytes (ANC), 36-93% in non-lymphocytic cells (NLC) and 50% or more in all cases in non-erythroid/non-lymphocytic cells (NENLC). Thus maturation arrest of blast cells was evident in HL, which corresponds to that of overt AML. Out of 20 cases treated with low-dose ara-C 13 cases (65%) achieved complete remission, but most of them relapsed early by manifesting hypocellular bone marrow again. In conclusion HL is a distinct clinical subtype of AML in the elderly, which can be clearly defined by 40% or less cellularity and 30% or more blasts in bone marrow. PMID- 7783352 TI - [Hematological neoplasm--how to treat low-grade lymphomas]. AB - Low-grade lymphomas are rare in Japan, comprising about 10% of non-Hodgkin's lymphomas. They are indolent in natural history with median survival of 7-10 years. Despite a good initial response to radiotherapy or chemotherapy, most patients (Pts), being incurable, ultimately die of their disease. Pts with clinical stage (CS) I/II disease are generally treated with locoreginal radiotherapy. Long-term survival of 60% to 70% and disease-free survival (DFS) of 50% to 55% have been reported. The more precise the staging procedures, the better the results. Chemotherapy used as a primary therapy or as an adjuvant to radiotherapy may improve DFS of pts with CS II with many sites of lymph node involvement or bulky disease. For CS III/IV disease there is no accepted standard therapy. There is no survival advantage for any of the different first-line treatment methods ranging from initial deferral of treatment albeit in highly selected pts, an alkylating agent +/- steroid hormone, to combination chemotherapy (C-MOPP, CHOP, ProMace-MOPP etc) +/- irradiation. The international index for prognostication of aggressive lymphoma has also been shown to be applicable to stratification of low-grade lymphomas. In future studies effectiveness of treatment strategies should be investigated with long-term DFS and improved quality of life being set as primary endpoints. PMID- 7783353 TI - [Multiple myeloma--diagnosis, prognostic factors and treatment]. AB - The problem of diagnosis, prognostic factors and the efficacy of therapies were investigated in 330 patients with multiple myeloma (MM) and 51 patients with benign monoclonal gammopathy (BMG)/monoclonal gammopathy of undetermined significance (MGUS). Seven out of 51 patients with BMG/MGUS were transformed into MM. The mean time to the transformation was 61.6 months. M protein level in these patients had been gradually and constantly increasing until the transformation in contrast with stable level in non-transformed patients. In MM there was one year difference between median survival from the time of diagnosis and start of chemotherapies. It depended on the deferral of treatment in patients with stage I myeloma. No difference of survival time was found between initial and differed therapy for stage I myeloma. Earlier therapy is not advantageous in this stage. Stages and immunoglobulin classes of MM were prognostic factors. Stage I or IgG myeloma had the longest survival and stage III or BJP myeloma had the shortest one. The new protocol, DMVM plus natural interferon alpha therapy induced high complete remission rate of 37.1% in initial treatment patients. The survival rate at three years from the treatment was 70%. PMID- 7783354 TI - [Diagnosis and treatment of essential thrombocythemia]. AB - Essential thrombocythemia (ET) is one of the chronic myeloproliferative disorders (MPD), clonal disorders of hematopoietic stem cell. The differential diagnosis from the other MPD and reactive thrombocytosis was described. The treatment of this disease was then stated with emphasis on the importance of control of platelet count. For the control, drugs to suppress the megakaryocytic proliferation are used, including busulfan, hydroxyurea, interferon-alpha and Anagrelide. The therapy for asymptomatic patients and pregnant women as well as patients with acute hemorrhage and thrombosis was also discussed. PMID- 7783355 TI - [Peripheral T-cell lymphoma with abundant ATL-like cells in the blood]. AB - A 69-year-old woman was admitted to our hospital because of leucocytosis and systemic lymphadenopathy. On admission, white blood cell count was 163,000/microliters, most of which consisted of flower-like cells with convoluted nuclei in the peripheral blood. In the abnormal lymphocyte cells surface-marker test by flow cytometry showed that they expressed CD2, CD3, CD4, CD29, CD45RA, and CD38, but not CD8, CD16, and CD25. Serum anti-Human T-lymphotropic virus type I (HTLV-I) antibody was negative in particle agglutination, enzyme-linked immunosorbent assay (ELISA) and western-blotting assay. HTLV-I proviral DNA in the abnormal lymphocyte cells was not detected by southern blotting hybridization technique. Moreover, HTLV-I provirus was not detected using a polymerase-chain reaction (PCR). A monoclonal rearrangement of the TCR-beta chain gene was evident by using DNA probe in southern blot hybridization. Because of the rapid progress of the disease, chemotherapy was started immediately after admission. Though, this patient became refractory, and she died about 1 year after admission. PMID- 7783356 TI - [Non-Hodgkin's lymphoma presenting as a soft tissue tumor in the connective tissue at the thigh]. AB - A 62-year-old man visited our hospital in July 1993, because of a right thigh mass which had grown gradually since two years previously. Physical examination revealed that the mass at the right thigh region, was elastic soft and about 15 x 10 cm in diameter, without regional lymph node swelling. An ultrasound study showed a hypoechogenic and mesh patterned mass. MRI revealed that the tumor was well defined from subcutaneous adipose tissue and skeletal muscle, indicating that it arose in connective tissue. Angiography demonstrated diffuse hypervascularization of the tumor, and Gallium scintigraphy showed remarkable accumulation at the tumor. Serum IgM was increased, which was proven to be an monoclonal hypergammopathy (IgM, lambda). Histological examination of a biopsied specimen obtained from the thigh mass revealed B cell lymphoma, lymphoplasmacytic cell type. The patient achieved a complete remission after surgical treatment following radiation and combination chemotherapy. PMID- 7783357 TI - [Epstein-Barr virus associated natural killer cell leukemia: report of an autopsy case]. AB - A 20-year-old female was admitted because of high fever, hepatosplenomegaly, severe hepatic dysfunction and coagulopathy. Peripheral blood showed pancytopenia and granular lymphocytes bearing the natural killer cell phenotype (CD2+CD3 CD16+CD56+CD57-TCR alpha beta-TCR gamma delta-) constituted 97% of leucocytes. Southern blot analysis of DNA obtained from peripheral blood mononuclear cells showed germ-line configuration of TCR beta, gamma and delta chain genes. EBV-DNA was detected in a single episomal form by using EBV-terminal repeat probe. Bone marrow findings were consistent with hemophagocytic syndrome and administration of VP-16 was effective transiently. After ten months she died from massive gastrointestinal bleeding. An in situ hybridization study identified EBV-RNA (EBER-1) in atypical lymphocytes infiltrating bone marrow, spleen and lymph nodes. Sections of liver showed steatosis and infiltration of T cells (CD3+ and EBER-1-negative) in the portal areas and few atypical lymphocytes in sinusoids. The patients developed an EBV-associated clonal proliferation of natural killer (NK) cells, but the clinical features were suggestive of chronic active EBV infection or virus-associated hemophagocytic syndrome (VAHS) rather than leukemia. Bone marrow transplantation for NK cell leukemia is an issue to be discussed. PMID- 7783358 TI - [Quantitative bleeding time]. AB - Bleeding time, which reflects the interaction of the platelets with the damaged vessel wall and the subsequent formation of the primary hemostatic plug, has been widely used in the diagnosis of bleeding disorders, especially platelet abnormalities. We have developed a computerized method to measure the bleeding pattern and the amount of blood loss from the bleeding time incision (quantitative bleeding time). In 87 normal subjects (51 males and 36 females), the bleeding time was 389 +/- 137 sec and the amount of blood loss was 15.7 +/- 7.2 microliters (mean +/- S.D.). The bleeding pattern was classified into four types (I-IV). Type II showed the prolongation of the bleeding time, continuous constant bleeding, and considerably large amount of blood loss from the incision. This type which includes severe von Willebrand disease and serious thrombocytopenia is related to the severe bleeding tendency. Type III exhibited the prolongation of the bleeding time keeping a trace of blood loss from the incision. In type III patients, the bleeding tendency was generally mild despite the prolonged bleeding time as in patients with moderate thrombocytopenia or aspirin ingestion. Measurement of bleeding pattern and blood loss will provide a useful information to evaluate the defect of primary hemostasis. PMID- 7783359 TI - [Detection of platelet aggregates using light scattering]. AB - Platelets play an important role in hemostasis and thrombosis. Evaluation of platelet function provides useful information on the diagnosis and cure of diseases associated with hemostasis and thrombosis. Among various platelet functions, platelet aggregometry is most widely used in clinical application. Platelet aggregation has been assessed by measuring the changes in the optical density of the platelet suspensions. However, this method has several shortcomings such as failure to detect the formation of small aggregates and lack of correlation between aggregate formation and changes in optical density. Thus, we have developed a new method of platelet aggregometry based on light scattering. This device emits laser beams against platelet aggregates and efficiently detects light scattering produced by these aggregates. The intensity and frequency of light scattering provides information as to the size and number of aggregates present in a limited area. By this method, we were able to determine several different modes of inhibitory effects on platelet aggregation. The high sensitivity of this method also allowed us to detect slight platelet activation, which had not been possible by the conventional method using changes in optical density. Clinical application of this method revealed frequent occurrence of spontaneous aggregation in diabetic patients and a close relationship between this phenomenon and diabetic complications. PMID- 7783360 TI - [Recent progress in evaluation of glycemic control by glycated protein and 1,5 AG]. AB - The aim of treatment of diabetes is to prevent the progress of diabetic complications. A recent report by the DCCT (Diabetes Control and Complications Trial) clearly shows the importance of strict glycemic control for prevention of diabetic complications. For this purpose, some markers for long-term glycemic control other than glucose concentration will be helpful, because glucose levels fluctuate too severely to assess whether they are precise. HbA1c is the longest established marker for glycemic control but still large interlaboratory variation is present. The standardized procedure for measurement of HbA1c was just proposed by the Japan Diabetes Society. Fructosamine is measured by a simpler procedure but many deoxidizing materials in serum especially superoxide may interfere with the reaction. Glycated albumin should be more reliable than fructosamine but a standard method of measurement has not been established yet. Future measurement of advanced glycation end product (AGE) should prove to be good marker for not only glycemic control but also diabetic complications or diagnosis of diabetes. The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary glucose excretion and may be useful as a marker of glycemic control and diagnosis of diabetes. PMID- 7783361 TI - [Plasma fatty acids, lipids, lipoprotein and macroangiopathy]. AB - Epidemiological studies have elucidated that diabetes mellitus (DM) is one of the risk factors of coronary heart disease and that DM often accompanies dyslipidemia. Dyslipidemia in DM can be classified as either quantitative or qualitative. Although dyslipdemia in DM is affected by the type of DM and glycemic conditions, the characteristics of dyslipidemia in DM, especially in NIDDM are the increase in triglycerides accompanied by the decrease in HDL cholesterol level. Recently, new commercial kits for measurement of atherogenic lipoproteins which increase in DM are clinically available. The usefulness of these kits in DM was reviewed. Polyacrylamide electrophoresis can detect IDL and Lp(a) qualitatively. It has also become possible to estimate Lp(a) quantitatively by ELISA, TIA and LIA methods. Remnant lipoprotein can be measured in the fraction unbound to anti-apo A1 and anti-apo B100 antibodies by immunoaffinity gel analysis. Apoproteins, apoprotein E phenotype, post-heparin lipoprotein lipase, and Lp AI (HDL with apo AI and without apo AII) can be measured by the commercially available kits. Modified LDLs (glycated, oxidative) increase in DM, but their measurements remain complicated at the moment. Analysis of plasma fatty acids by gaschromatography is useful for dietary assessment. The measurement of these new markers seems to be useful to assess the extent of atherogenic risk in DM. PMID- 7783362 TI - [Determinations of microproteinuria in early diabetic nephropathy]. AB - Microalbuminuria, transferrin and IgG were determined in the urine of diabetic patients with normal renal function. Microalbuminuria was assayed by the immunoturbidity method, transferrin by the latex agglutination method and IgG by the ELISA method using biotin labelled IgG.HRP labelled protein G. The correlation between microalbuminuria and urinary transferrin concentrations was high (r = 0.902). However, a low titer of transferrinuria was observed, (25.5%) among the patients with microalbuminuria; a wider distribution of transferrinuria was noted than microalbuminuria. Determination of transferrinuria did not appear to be superior to the determination of microalbuminuria in early diabetic nephropathy. The urinary IgG levels assayed by ELISA using biotin labelled IgG.HRP labelled protein G method were distributed from zero to 5 mg/g Cr in the patients with normoalbuminuria. The reference intervals of the urinary IgG concentration should be settled below 5 mg/g Cr. In the patients with microalbuminuria, the concentration of urinary IgG showed a wide variation and no correlation between concentrations of microalbuminuria and urinary IgG was noted (r = 0.02). Determination of urinary IgG is not useful as an early diagnostic procedure for diabetic nephropathy. PMID- 7783363 TI - [Islet cell antibodies]. AB - Islet cell antibodies (ICA) are a marker of insulin-dependent diabetes mellitus (IDDM). ICA are detected in 60-80% of the patients with IDDM at the onset of the disease. The presence of ICA in patients with non-insulin-dependent diabetes mellitus (NIDDM) indicates that the patients are likely to develop IDDM. However, as ICA are measured by the indirect immunofluorescent method, the reliability of the ICA assay is not high in some institutes. Use of the pancreas tissue having high antigenicity is recommended as one solution for a reliable assay. Standardization of the ICA assay is under way with the use of an ICA positive standard sera as 80 JDF units. Anti-glutamate decarboxylase (GAD) antibody assays using a radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) have recently been developed. The significance of anti-GAD antibodies is comparable to that of ICA. Since the anti-GAD assay is reproducible and easy to perform, it should be used widely in parallel with the ICA assay. PMID- 7783364 TI - [Genetic diagnosis of diabetes mellitus]. AB - NIDDM is likely to have a major genetic component in view of the different prevalence between ethnic groups, the familial clustering, and the high concordance in monozygotic twins. Linkage analysis of extended pedigrees of patients with maturity-onset diabetes of the young (MODY) identified the glucokinase gene mutations. Specific phenotypes have also led to the discovery of the insulin gene mutations in patients with high insulin or proinsulin levels, to the insulin receptor mutations in patients with marked insulin resistance, and to the mutations in mitochondrial DNA associated with deafness and maternal inheritance. These four types of diabetogenic gene mutations account for only a minor proportion of NIDDM. Direct screening for mutations in candidate genes with single-strand conformation polymorphism or heteroduplex screening or with direct sequencing in the diabetic patients with the appropriate pathophysiological abnormality can be a successful strategy. Genetic diagnosis provides clear definite diagnosis and specific therapies, such as IGF-1 for the insulin receptor mutations and coenzyme Q10 for the mitochondrial gene mutations. PMID- 7783365 TI - [The glutamic acid decarboxylase (GAD) antibodies and their clinical significance]. AB - Since it was reported that the 64kD antigen that had been found to be the target of autoantibodies in the sera from IDDM patients was the same as GAD, GAD antibodies have been one of the focuses of many investigations. In this study, we developed a sensitive radioimmunoassay (RIA) system for GAD antibodies in human sera using native GAD purified from the pig brain. To confirm the relevance of pig GAD as the target antigen, we compared the sequences and antigenic activities among pig, rat and recombinant human GAD65. Based on the data from our and other laboratories, the homology of amino acid sequences between pig and human GAD65 was 96.4%. The coefficient of correlation between the results of human and pig GAD RIA was 0.948. The GAD antibody study group confirmed the clinical usefulness of GAD antibodies not only for the diagnosis of IDDM but also slowly progressive IDDM. PMID- 7783366 TI - [An interlaboratory standardization of HbA1c determination in Japan]. AB - A survey of the actual state of interlaboratory differences in HbA1c values revealed a great variation of the values among 107 laboratories throughout Japan; the coefficient of variation (CV) for measurements of fresh blood samples was as high as 10.5%. On the basis of this results, it became apparent that this large interlaboratory variation was mainly due to differences in evaluation of a labile HbA1c component and in values measured with an instrument of one manufacture with another. To verify this assumption, we asked the laboratories to measure only a stable component using common calibrations. These procedures resulted in a marked reduction of the interlaboratory difference in HbA1c values; the CV decreased to 2.82%. The reference intervals of HbA1c calculated from the HbA1c results of 725 healthy subjects measured using the standardized procedure was from 4.3% to 5.8%. PMID- 7783367 TI - [Telepathology]. AB - Telepathology, introduced in 1986 by Weinstein, was not adopted in Japan because its image could not be transmitted by the National Television Standard Committee (NTSC) transmission. In 1990 a new system of Hi-Vision (HDTV) with 1125 lines, was implemented in Yamagata University and was highly evaluated. This success was followed by new developments both in NTSC and HDTV telepathology systems. Real time HDTV images are transmitted via optical fiber cables for in-house hospital operations. Static HDTV and NTSC images are transferred via integrated services digital network (64 Kbit/s and 1.5 Mbit/s). Today telepathology networks are extending all over the country. PMID- 7783369 TI - [Detection of heterogeneous MRSA by using the PCR method and population analysis]. AB - To assess the clinical usefulness of the PCR method for the detection of methicillin-resistant Staphylococcus aureus (MRSA) by targetting the mecA gene, we surveyed 150 clinical isolates of Staphylococcus aureus and compared the results of the PCR method with those of the standard broth microdilution method. Fifty-four isolates (36%) were positive for the mecA gene and two of them, presenting coagulase type IV, were recognized as susceptible strains by microdilution method, while all the other mecA positive strains were drug resistant. Population analysis revealed that these two strains were heterogeneous in terms of drug-resistance and composed of two populations of cells; i.e., relatively susceptible cells and highly resistant cells. The discrepancy between the phenotypic expression (drug-resistance) and the genotype (mecA gene) seems to be due to the small percentage of highly resistant cells. Drug-resistant colonies could be induced in these strains by the contact with methicillin, indicating the selective increase of the population of resistant cells by a passage in the drug. These observations suggest that it is clinically important to detect the resistance-inducible strains (prototype MRSA) by using the PCR method and population analysis. PMID- 7783368 TI - [Immunohistochemical study of proliferation index of astrocytomas classified by new histopathological grading]. AB - A new grading method of astrocytoma, proposed by Daumas-Duport et al, was based on four criteria:nuclear atypia, mitosis, necrosis and endothelial proliferation (0 criteria = Grade 1, 1 criteria = Grade 2, 2 criteria = Grade 3, 3 or 4 criteria = Grade 4). To elucidate the correlation of the classification based on four criteria, cellularity and proliferative activities, we studied proliferating index of 67 astrocytomas, using immunohistochemical staining for Ki-67 antibodies (MIB-1). A new grading method was related to proliferating index in this study, however, cellularity of tumor cells was not related to proliferating index. In this study, endothelial proliferation was invariably seen in high grade(Grade 3 and 4) astrocytomas. These tumor vessels were associated with dysfunction of blood-brain barrier and some growth factors accelerated to tumor cell proliferation. Relation between histopathological grade of astrocytoma and proliferation index was supposed, and new grading system was thought to be useful for routine pathological examination. PMID- 7783370 TI - [Detection of nuclear antigen within the leukemic cells using immunocytochemical technique]. AB - Immunocytochemical methods were examined for their sensitivity in the detection of nuclear antigens (proliferating cell nuclear antigen, Ki-67 associated proliferative antigen and p53 protein) in the leukemic cells. A comparative study of the biotin streptavidin enhanced peroxidase technique, the biotin streptavidin enhanced alkaline phosphatase technique and the indirect immunoperoxidase technique showed that the indirect immunoperoxidase technique was more sensitive than the other techniques for detecting p53 protein. The results of several fixation methods demonstrated that formalin and methanol, formalin and ethanol (1:9) and buffered formalin acetone gave good results for detecting p53 protein. In the eosinophils and neutrophils the endogenous peroxidase reaction disappeared after microwave heating for over three minutes. Thus enzyme pre-blocking of blood smears could be omitted. Four solutions for microwave treatment were tested. Excellent antigen retrieval was obtained with pH6.4, pH7.4 phosphate buffer saline and pH6.0 citric acid. However, the nuclear antigens could not be retrieved and the positive reaction could not be obtained after the treatment with distilled water. The optimal microwave heating time was five to ten minutes. The indirect immunoperoxidase technique performed using microwave treatment under these optimal conditions may be potentially applicable for detecting low levels of nuclear antigens in the leukemic cells within conventional blood smears. PMID- 7783371 TI - [Phenotypical diagnosis of Japanese chronic lymphocytic leukemia--an international cooperative study based on the French-American-British classification of mature B-cell leukemias]. AB - To better understand the accuracy in the diagnosis of chronic lymphocytic leukemia (CLL) and characterize the clinical features of CLL in Japan, where the disease is extremely rare, an international cooperative study was conducted by hematologists between Japan and UK. Blood and bone marrow films from 36 patients with a possible-diagnosis of CLL were referred to two laboratories of Nagasaki University Hospital (Nagasaki) and Royal Marsden Hospital (London). According to the FAB criteria, typical CLL 16 and CLL/PL 2, a subtype of atypical CLL, were completely accordant in diagnosis. However, phenotypical diagnosis of CLL mixed, the other of atypical CLL, and intermediate lymphocytic leukemia (ILL) in leukemic phase often gave inconsistent results. Especially, 8 cases of atypical CLL designated as likely CLL were equivocal between CLL and ILL, suggesting clinical feature more close to typical CLL than ILL. This indicates the presence of a relatively high incidence of atypical CLL in Japan which dose not exactly fit with the FAB Criteria. Finally, we would like to emphasize that an international cooperative study allows improvement of accuracy in diagnosis and better understanding of the disease entity of lymphoid malignancies, having on ethnically different morbidity. PMID- 7783372 TI - [The ABO blood groups-dependent reference intervals for serum alkaline phosphatase isozymes and total activity in individuals 20-39 years of age]. AB - Reference intervals of the activity of serum alkaline phosphatase isozymes (AP IZ: high molecular-, liver-, bone- and intestinal-types) were determined according to the ABO (blood type) system in 200 healthy subjects aged 20-39 years. AP activity was determined according to the JSCC method. AP-IZ was stained by the formazan method after isolation by TITANIII-Lipo plate electrophoresis. For the electrophoresis, treated serum with neuraminidase and untreated one were concomitantly used for detecting liver AP and bone AP respectively. As a result of comparison of mean AP-IZ activity among the groups divided according to the ABO system, total AP, intestinal AP and liver AP activities in the type B and O persons were significantly higher than in the type A and AB persons. It is well known that the activities of total AP and intestinal AP in type B and O persons are higher than in type A and AB persons, but there have been no reports showing that the activity of liver AP in type B and O persons is higher than in type A and AB persons. Furthermore, in the type B and O persons there was a low correlation (r = 0.195, p < 0.05) between the activities of liver AP and intestinal AP. The present assessment included subjects in the age group (20-39 years) considered not to show fluctuations in the activity of bone AP, which is influenced by age. The above findings should be investigated in regard to other age groups. PMID- 7783373 TI - [Clinical significance of serum troponin T following coronary artery bypass surgery]. AB - We evaluated the clinical significance of serum cardiac troponin T(TnT) following coronary artery bypass surgery (CABG) as an indicator of cardiac damage during the operation. We studied 21 patients who underwent CABG and 8 patients who underwent open thoracotomy for lung disease. In the CABG patients, serum TnT levels showed roughly biphasic release kinetics, with a peak less than 10h postoperatively and a second peak on or about the fourth day. The serum TnT levels at 0 and 10h postoperatively were 8.58 +/- 1.07 (mean +/- SE) and 9.19 +/- 1.35ng/ml, respectively, levels were 30-40 times higher than the cut-off value of 0.25ng/ml. On the fourth day after CABG, serum TnT in the 3 graft groups (7.21 +/ 2.56ng/ml) was significantly higher than in the 1 or 2 graft groups (2.57 +/- 0.05 and 2.53 +/- 0.46ng/ml, respectively). The peak serum TnT level of the patients with perioperative myocardial infarction was 34.6 +/- 5.29ng/ml, which was significantly higher than in the patients without specific evidence of perioperative infarction. On the other hand, in the patients undergoing thoracic surgery for lung disease, serum TnT showed no postoperative increase. In conclusion, serum TnT appears to be a specific marker of cardiac damage after CABG, and may be useful for the diagnosis of perioperative myocardial infarction. PMID- 7783374 TI - [Recent clinical research of familial adenomatous polyposis]. PMID- 7783375 TI - [Epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer with applying a method of case-control study--a study of a efficient screening programme for stomach cancer]. AB - An epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer was conducted with applying a method of case-control study. And also in order to carry out an efficient screening programme, the age groups who should be intensively recommended to receive screening and an optimal screening time interval since the last test were analyzed. 527 cases of men and 273 of women, dying of stomach cancer in the years 1981-1989 in the Awa region of Chiba prefecture, were identified from Chiba Cancer Registry. For each case, 3 controls were drawn at random from Awa living residents (about 162000 inhabitants at 1989 national census), with being matched strictly according to the district of residence, sex and born within 3 years of birth-year. For both cases and controls, the information about the screening history until the date of diagnosis of the case in each matched set was collected respectively from comparison with the screening certification. The results showed a relative risk of 0.417 (99% CI 0.284-0.612) in ever screened men compared with never screened and 0.480 (99% CI 0.280-0.823) in women. The significant reduction in risk was intensively observed on age groups 40-74 years among men and 50-69 years among women and the protective effect continued at most in the following three years since last screening. For an efficiency of screening programme, these age groups should be intensively recommended to receive screening and it is allowable that an optimal screening time interval since last negative test is at most 3 years for general attendance. PMID- 7783376 TI - [Macroscopic characteristics of depressed type early gastric cancer special reference to their mucosal localizations]. AB - Macroscopic characteristics of 143 lesions from 138 cases of depressed type early gastric cancer less than 2.0cm in the major axis (74 lesions of undifferentiated cancer, 69 lesions of differentiated cancer) were studied with respect to the localization in the gastric mucosa divided into 3 areas (area F: fundic gland region, 36 lesions, area I :intermediate gland regions, 29 lesions, area P :pyloric gland region, 79 lesions). (1) All 36 lesions in the area F were of the undifferentiated type. Narrowing and/or interruption of the folds were found in 83%. The abnormal folds were found in 97% of the lesions found in the area where the mucosal folds were present. (2) 72% lesions in the area I were determined to be undifferentiated cancers. Uneven depressed surface was observed in 95% of the undifferentiated cancer. Steep depressed margine was found in their 86%. Narrowing and/or interruption of the folds were detected in their 81%. In cases of differentiated cancer, the findings of folds both on the depressed surface and margin were scarcely observed. (3) The undifferentiated cancer was diagnosed in 22% of the lesion in the area P. In 18% and 76% of them, uneven depressed surface and steep depressed margin were observed respectively. Narrowing and/or interruption of the folds were recognized in only 6%. Although these abnormal macroscopic findings were less in this area, the marginal elevation was found in 59%. In differentiated cancer of this area, the presence of marginal elevation was the highest up to 72% compared with cancers in the other areas. PMID- 7783377 TI - [Effects of centrally administered NPY on stress induced gastric ulcers in the rat]. AB - We investigated the central effects of neuropeptide Y (NPY) on stress-induced gastric ulcers in water immersion rats. Intracisternally administered NPY dose dependently aggravated, but intravenously administered NPY did not affect stress ulcers in rats. Intraperitoneal pre-treatment of atropine completely blocked the central effect of NPY, but neither pyrilamine nor cimetidine affected. Intracisternal administration of NPY aggravated stress ulcers not through histamine mediated mechanism but by parasympathetic pathway. It is suggested that centrally administered NPY acted by the inhibition on gastric motility and by the suppression on gastric mucosal blood flow rather than by the stimulation on gastric secretion in rats. PMID- 7783378 TI - [Residual gastritis after gastrectomy and Helicobacter pylori--its clinical significance]. AB - Residual gastritis after gastrectomy brings the various symptoms such as abdominal pain, nausea, emesis and loss of appetite, and often hazards quality of life of the patient. Bile reflux to the stomach is believed as one of the important pathogenesis of residual gastritis, however the prevention for bile reflux cannot always heal the gastritis. Helicobacter pylori (H. pylori) is considered as one of the most important pathogenesis of gastroduodenal ulcer and gastritis, and H. pylori may possibly cause residual gastritis after gastrectomy. However, the association between infection with H. pylori and the residual gastritis has not revealed yet. In the present study, the association with H. pylori and the residual gastritis after gastrectomy was investigated in 56 patients who had undergone gastrectomy before. Twenty-four patients (42.9%) had H. pylori infection at their stomachs and the incidence of the infection in the patients with gastrectomy was significantly higher with subtotal gastrectomy. As for the histological gastritis score of Rauws (Rauws' score), Rauws' score of H. pylori positive group was significantly higher than H. pylori negative group. Furthermore, the eradication of H. pylori for the patients with serious symptoms of gastritis improved the symptoms and decreased significantly Rauws' score. These results suggest that H. pylori was associated with the pathogenesis of residual gastritis after gastrectomy. PMID- 7783379 TI - [A successful treatment of jejunal leiomyosarcoma accompanied with liver metastases]. PMID- 7783380 TI - [A case of primary signet-ring cell carcinoma in the 3rd part of the duodenum]. PMID- 7783381 TI - [A case of digestive fract T-cell malignant lymphoma with clinical course of twenty years]. PMID- 7783382 TI - [A case of pyogenic granuloma in the sigmoid colon]. PMID- 7783383 TI - [A case report of colon cancer in ulcerative colitis followed up for 9 years after the detection of high-grade dysplasia on biopsy]. PMID- 7783384 TI - [A case of actinomycosis of the greater omentum]. PMID- 7783385 TI - [A case of chronic active hepatitis C presenting heart failure during interferon alpha 2 alpha therapy]. PMID- 7783386 TI - [An autopsy case of multiple myeloma with veno-occlusive disease of the liver induced by ionized radiation]. PMID- 7783388 TI - [A new trial of intraluminal ultrasonography in the diagnosis of gallbladder diseases by endoscopic transpapillary catheterization in the gallbladder technique (ETCG technique)]. PMID- 7783387 TI - [A case of HCV-RNA positive liver cirrhosis with hyper-gamma-globulinemia and high titers of ANA, accompanied by hypothyroidism]. PMID- 7783389 TI - Correlation of alpha-1-antitrypsin (PI) polymorphism between blood and semen. AB - The correlation between isoprotein types of alpha-1-antitrypsin (PI) in blood and semen samples from the same individual was determined in 48 Japanese men by the combined technique of isoelectric focusing with immobilized pH gradients and immunoblotting. Five common PI types (M1, M1M2, M1M3, M2 and M2M3) were detected in the blood plasma samples. However, PI-specific bands in semen migrated more cathodally than those in plasma into a pI region of approximately 5.05, and about 17% of the semen samples could not be phenotyped: the rest were easily phenotyped and their PI types were found to correlate with the type found in the corresponding blood samples. PI typing could therefore provide an additional discriminant characteristic for the forensic examination of individualization from semen samples. PMID- 7783390 TI - [Analysis of sex chromosomal DNA markers by a molecular biological method and it's application to forensic medicine]. AB - We attempted sex and individual identifications of several forensic specimens by detecting various sex chromosome-specific sequences by the polymerase chain reaction (PCR) method. The specimens were 30 blood stains that were attached to gauze and stored for 11 months -15 years (15 males, 14 females and 1 of unknown gender) and 10 bleached white bones (8- about 10000 years after death). Of the known 29 blood stains, the sex determination rate was the highest by DYZ-1 (amplified DNA fragment = 149bp, about 3000 copies on Y chromosome) recombinated with DXZ-1 (28 of the 29 samples) although 27 samples could be determined by DYZ 1 (amplified DNA fragment = 1000bp, about 3000 copies on Y chromosome) recombinated with DXZ-1. The sex determination rate was relatively low by DYZ-3 (amplified DNA fragment = 170bp, about 100 copies on Y chromosome) recombinated with DXZ-1 (23 of the 29 samples). The sex determination rate by two single locus markers, PAB or Amelogenin was markedly low (7 and 9 of 29 samples, respectively). The sex determination rate by the 27H39 locus was 27 of the 29 samples; 14 of the 15 male were determined (A = 186bp, 1; B = 190bp, 7; C = 194bp, 5; D = 198bp, 1; E = 202bp, 0). One unknown gender could be identified as male by multiple locus markers, but could not be identified by any single locus markers except for the 27H39 locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783392 TI - [Arterial oxygen saturation monitoring of sleeping infants by pulse-oximeter- effect of sleeping position on arterial oxygen saturation in infants]. AB - Monitoring of the arterial oxygen saturation (SaO2) in two sleeping infants was reported. They were a couple of female twins and had grown up normally after admission to NICU (Neonatal Intensive Care Unit) for a month. We investigated their SaO2 with the puls-oximeter at the terms between the 2nd and the 10th month. There was no significant difference between SaO2 in prone positions (n = 29) and that in supine positions (n = 30). In the infant with the sniffing conditions, however, SaO2 in prone positions seemed to be slightly lower than that in the healthy conditions. The slightly low SaO2 would give no effects on the healthy infants, but it may cause ALTE (Apparent Life Threatening Event) or death from SIDS (Sudden Infant Death Syndrome) to some infants who are not in good health and/or who are prone to get into ALTEA or SIDS. Especially, in the sniffing condition with hyperthermia, as the oxygen dissociation curve sifts to right and SaO2 degradation appears easily, sudden infant death may be possible to happen in prone position. PMID- 7783391 TI - [Simple determination methods for blood grouping from biological stains. 1. Immunologic gold colloid aspiration test and dot ELISA test by membrane aspiration method for determining ABO blood groups from saliva specimens]. AB - Two immunologic tests using nitrocellulose membrane and an aspiration device were applied to determine the ABO blood groups and secretor status from saliva specimens. First, immunologic gold colloid membrane aspiration test (IMAT) was performed with orange-red colloidal gold particles (GP) sensitized with anti-A or anti-B antibody or anti-H lectin (A chicken antiserum to O secretor saliva was also used as an anti-H reagent in some experiments). The boiled saliva specimens were serially diluted and dotted to the nitrocellulose membrane, which was equipped to a disposable aspiration kit, and the antibody- or lectin-coated GP was aspirated through the membrane. The stained saliva changed red by the immunologic binding of the GP. Test results could be obtained within some minutes. Detection limits of IMAT shown by saliva dilution were 1:100 to 1:10,000 for secretor salivas, whereas those for non-secretor salivas were 1:10 or lower. Second, a revised dot ELISA was performed by using the membrane aspiration device. The requisite time for this test (Dot ELISA-A) was 40 to 45 minutes, whereas that for conventional dot ELISA was 3 to 4 hours. The detection limits of the dot ELISA-A shown by the saliva dilutions were 1:1,000 to 1:100,000 for secretor salivas, whereas those for non-secretor salivas were 1:1,000 or below. PMID- 7783393 TI - Pharmacokinetics of ethanol drinking--absorption kinetics and first-pass effect. AB - The pharmacokinetics of alcohol drinking was studied in male rabbits. Various doses (D) of ethanol (0.25, 0.5, 1, 2 and 3 g/kg BW) were administered perorally to the animals and blood alcohol (ethanol) concentration (BAC) was measured. Simultaneous multiline fitting was attempted using the BAC-time curves of 5 peroral doses and of 5 intravenous doses. The two-compartment open model with parallel first-order and Michaelis-Menten elimination and first-order absorption kinetics was concluded to be the best model. To estimate the value of the absorption rate constant (ka) and the bioavailability (F) at each dose, curve fitting was also attempted by using a single BAC-time curve. The F value decreased with a low dose (0.25 g/kg), but complete systemic bioavailability was noted in higher doses. A first-pass effect was suggested to occur with the low dose. With low doses, the peak BAC might be too low to saturate the ethanol metabolism. The conventional method using area under the BAC-time curve (AUC) underestimated the F value. The other conventional method using theoretical BAC at time zero (C0) [F = C0oral x D(i.v.)/C0i.v. x Doral)] was compared to the AUC method. The estimated F value by this C0 equation method was closer to it by curve fitting than that by the AUC method. The effects of various ka, F and D values were also studied using a computer simulation. Consequently, the conventional AUC method was concluded to overestimate the first-pass metabolism of ethanol. The C0 equation method is thought to be more useful. PMID- 7783394 TI - [Immunology of tuberculosis and cytokines]. AB - One of the unique features characterizing human tuberculosis (TB) is its pathogenesis. The pathogenesis of TB involves cell-mediated immune responses against Mycobacterium tuberculosis. Concisely, macrophages activated by various soluble mediators or cytokines released through the cellular interactions after infection with M. tuberculosis play a pivotal role in the pathogenesis of human TB. In fact, very complex cellular interactions are going on within the host after infection with or endogenous reactivation of M. tuberculosis. Cells communicate by cell-cell contact and by the release of mediators which may originate locally, called cytokines. In TB infection, macrophages can be activated by two ways; directly with mycobacterial organisms or lipid fractions of their cell walls at the earlier phase of infection, and indirectly with cytokines produced by CD4+ T cells specifically activated by mycobacterial peptide antigens at the later phase of infection. The various clinical features of TB are the summarized outcome of cell to cell interactions mediated by diverse cytokines produced by various immune cells which are initially triggered by M. tuberculosis infection. CD4+ T cells can be classified into two subsets according to the patterns of cytokines they produce; Th1 cells give rise to cell-mediated immunity and are characterized by the production of IL-2 and IFN-gamma, whereas Th2 cells are more efficient in mediating antibody production and secrete IL-4, IL-5, IL-6 and IL-10. Th2 cells can control Th1 cells and vice versa. Th2 cells therefore inhibit the production of cytokines by Th1 cells by releasing IL-4 and IL-10. Infection with mycobacteria stimulates macrophage IL-12 production which appears to act directly on naive CD4+ T cells to induce Th1 development and initiation of cell-mediated immunity. IL-12 is a critical component in the development of cell-mediated immunity. In addition, IL-12 also activates NK cells and gamma/delta T cells, both of which secrete various macrophage-activating factors to kill M. tuberculosis. One of the structural characteristics of M. tuberculosis is the cell wall rich in lipid components. Of importance among various biological activities of the cell wall lipids is the stimulation of mononuclear phagocytes to produce a certain number of cytokines or monokines including IL-12 and IL-10, both of which play important roles in regulation of immune responses in mycobacterial infection and in pathogenesis of TB.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7783395 TI - [An outbreak of tuberculosis involving foreign workers from South America]. AB - A twenty-four year old male Peruvian of Japanese origin, who came to Japan in September 1990 and had been working in a minor factory in a rural area, was admitted to a hospital in March '91 with severe cough. Smear examination of his sputum smear was positive for acid-fast bacilli and his chest X-ray showed multiple cavities (Index case). Subsequent contact examination identified further four patients with pulmonary tuberculosis among his colleagues in the factory, all of whom lived in the same house with the index case. During following three years, further six patients with mycobacteriosis, two Peruvians and four Japanese, were found among the employee of that factory. M. tuberculosis was cultured from the sputa obtained from seven of these eleven patients. Another patient was diagnosed as non-tuberculous mycobacteriosis. Restriction fragment length polymorphism (RFLP) analysis carried out with five strains of M. tuberculosis isolated from these patients revealed the identical RFLP pattern which is uncommon in Japan. Still more, an isolate from another patient was subjected to RFLP analysis by chance, and was found to show the same RFLP pattern. Later epidemiological study revealed that the last patient, a 53 year old saleswoman of boxlunch, might have some contact with the index case at her booth. Though RFLP analysis was not done for the isolate from the index case, from the identity of RFLP patterns of other isolates, clinical course and epidemiological study, it is considered that six patients were certainly, and two others were probably infected from the index case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783396 TI - [A case of eosinophilic pneumonia associated with Mycobacterium avium infection]. AB - A 54 year-old woman was admitted with cough and high fever. Computed tomographic scan of the chest showed bilateral patchy infiltrates, predominantly in the upper lobes. Eosinophils in the bronchoalveolar lavage fluid (BALF) accounted for 19% of BALF cells. Furthermore, Mycobacterium avium was isolated from a bronchial washing from the upper area of the right lung (S3) and a sample of sputum which had been submitted for microbial examination about 1 month before admission by another clinic. Based on these finding's the diagnosis of eosinophilic pneumonia associated with Mycobacterium avium infection was established. The infiltrates of the lung rapidly decreased after administration of antituberculous agents. The simultaneous presentation of eosinophilic pneumonia and Mycobacterium avium infection has not been previously reported. Because of the efficacy of antituberculous agents in this case, we concluded that Mycobacterium avium was a cause of eosinophilic pneumonia. PMID- 7783397 TI - [The 69th annual meeting special lecture. Present situation of leprosy]. AB - Many leprosy patients have deformity or disability owing to the characteristics of Mycobacterium leprae i.e. M. leprae affects skin and peripheral nerve. Optimum growth temperature of M. leprae was estimated by clinical manifestations and animal experiments, and it was concluded that the optimum temperature is 33 degrees C, and this characteristic of M. leprae may be one of the reason why M. leprae affects skin tissue. There was no reliable treatment of leprosy before 1943, but effectiveness of promin against leprosy was proven in 1943, and chemotherapy of leprosy was gradually improved especially since 1960 after the discovery of mouse footpad inoculation of M. leprae. In vitro cultivation technique of M. leprae is still unestablished, but susceptibility of ninebanded armadillo to M. leprae was discovered in 1970. Supply of M. leprae collected and purified from M. leprae infected armadillo tissue became available, then biochemistry, immunology and molecular biology of M. leprae was improved significantly. Ridley-Joppling's classification of leprosy i.e. two types (tuberculoid and lepromatous) and two groups (indeterminate and borderline) classification is being adopted at present. Rifampicin, DDS (dapsone) and clofazimine (lamprene) are widely used for chemotherapy of leprosy. WHO is recommending Multidrug Therapy (MDT) of leprosy i.e. administration of rifampicin and DDS for paucibacillary group, administration of rifampicin, DDS and clofazimine for multibacillary group. About 2.4 million leprosy patients are registered and under chemotherapy in the world at present, and about five hundred thousand new patients are being registered every year. Target of leprosy elimination by WHO is prevalence rate of leprosy should be less than one per ten thousand in every country.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783398 TI - Heparin lowers blood pressure: biological and clinical perspectives. PMID- 7783399 TI - Evaluation of the lithium clearance method: direct analysis of tubular lithium handling by micropuncture. PMID- 7783400 TI - Albumin interaction with the glomerular capillary wall in vitro. AB - The binding of albumin to the glomerular capillary wall was studied using albumin gold in perfused kidneys, the interaction of [3H]albumin with isolated glomeruli at 37 degrees C and 4 degrees C and the interaction at [3H]albumin with purified basement membrane. The albumin-gold was found to bind predominantly to the basement membrane and this interaction could be dissociated with high concentrations of albumin. There was binding of albumin to isolated rat glomeruli which exhibited temperature dependence. Glomeruli exhibited a binding site at both 37 degrees C and 4 degrees C with an association constant in the range of 1 to 3 x 10(4) M-1 that bound 7 x 10(13) molecules/glomerulus. At 37 degrees C, however, there was anomalous Scatchard binding behaviour at relatively higher concentrations of albumin (30 to 50 mg/ml) which could be due to either glomerular cell uptake or the appearance of multiple binding sites or both. The binding of albumin to isolated glomeruli and the glomerular albumin levels in isolated kidney perfusion could largely be accounted for by the binding of albumin to the glomerular basement membrane. The albumin binding to glomeruli at 37 degrees C was enhanced by Pronase digestion and heparinase digestion, but remained unchanged following trypsin treatment or neuraminidase treatment. Similarly, albumin was shown to bind to purified basement membrane preparations. This binding was also enhanced (approximately 80 times) by heparinase digestion but remained unchanged after digestion with chondroitinase ABC or hyaluronidase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783401 TI - Modulation of sodium-coupled uptake and membrane fluidity by cisplatin in renal proximal tubular cells in primary culture and brush-border membrane vesicles. AB - The proximal tubule appears to be the main target for the adverse effects of cis diamminedichloroplatinum (II) (cDDP). We evaluated the early effects of cDDP at concentrations (3 to 67 microM) lower that those which alter cell viability, on three apical transport systems and on the physical state of the brush border membrane (BBM) in rabbit proximal tubule (RPT) cells in primary culture. The maximal effect, corresponding to a 30% decrease in Na(+)-coupled uptake of phosphate (Pi) and alpha-methylglucopyranoside (MGP) and a twofold increase in Na(+)-coupled alanine uptake, was obtained at 17 microM (5 micrograms/ml) cDDP and occurred through a modification of their affinity. At this concentration, cDDP increased BBM fluidity and decreased the BBM cholesterol content by 28%, without increasing the permeability of tight junctions. To clarify the role of cDDP-induced increase in BBM fluidity on alterations of Na(+)-coupled uptake, these parameters were also investigated in BBM vesicles isolated from rabbit renal cortex directly exposed to cDDP. cDDP induced a concentration-dependent inhibition of Na(+)-coupled uptake of MGP, Pi and alanine in BBM vesicles from the renal cortex, associated with a decrease in protein sulfhydryl content, without modifying BBM fluidity. Our findings strongly suggest that the cDDP induced increase in BBM fluidity in RPT cells results from an indirect mechanism, possibly an alteration of cholesterol metabolism, and did not play a major role in the cDDP-induced inhibition of Na+/Pi and Na+/glucose cotransport systems that may be mainly mediated through a direct chemical interaction with essential sulfhydryl groups of the transporters. PMID- 7783402 TI - High glucose concentrations and protein kinase C isoforms in vascular smooth muscle cells. AB - High extracellular glucose activates protein kinase C (PKC), a family of kinases vital to intracellular signaling. However, which PKC isoforms are involved and where in the cell they operate is unclear. We tested the hypothesis that only those PKC isoforms binding to diacylglycerol (DAG) are activated by high glucose. We also reasoned that the isoforms would translocate to different parts of the cell, where they presumably serve different functions. The PKC isoforms alpha, beta, delta, epsilon, and zeta were studied. Twenty mM glucose caused an increase in total PKC activity at six hours, which was maintained at 24 hours. High glucose decreased the angiotensin II-induced calcium signal. This effect was reversed by preincubating the cells with the PKC inhibitor staurosporine. Glucose induced a translocation of all PKC isoforms except PKC zeta by Western blot. Confocal microscopy showed that PKC alpha, beta, and epsilon were translocated into the nucleus. PKC delta showed strong association with cytoskeletal structures. The effects were sustained at 24 hours for PKC isoform beta and to a lesser extent for PKC delta and epsilon, but not for PKC alpha. Thus, PKC isoforms differ in their propensity to be activated by high glucose. Those isoforms binding to DAG are activated. Both cytoskeletal and nuclear signaling may be involved. PMID- 7783403 TI - Non-iron mediated alteration in hepatic transferrin gene expression in the nephrotic rat. AB - Both transferrin and the iron it carries are lost in the urine in the nephrotic syndrome. Patients may develop hypochromic microcytic anemia and synthesis of transferrin, a protein regulated in large part by iron availability, is increased. Transferrin synthesis has also been reported to be increased in liver slices from rats with hereditary analbuminemia, and their plasma transferrin levels are increased, suggesting that transferrin synthesis may be stimulated by processes other than iron depletion in this hypoalbuminemic condition. Transferrin metabolism was studied in rats with Heymann nephritis (HN), in a strain of Sprague-Dawley (SD) rats with hereditary analbuminemia [Nagase analbuminemic rats (NAR)], and in normal SD rats. Plasma transferrin concentration and mass was decreased significantly in HN, but increased in NAR. Transferrin synthesis was increased both in NAR (measured either as the disappearance of [125I] labeled transferrin or as the incorporation of [3H] phenylalanine) and in HN (incorporation of [3H] phenylalanine). The fractional rate of transferrin catabolism was unchanged in NAR. Thus transferrin mass was increased in NAR entirely as a consequence of increased synthesis. Transferrin and albumin synthesis correlated with one another in both HN and SD (P < 0.001). Transferrin mRNA was increased in both HN and NAR and was unaffected by administration of iron to HN. Hepatic transferrin and albumin mRNA levels were also correlated positively in HN and SD, suggesting that increased hepatic synthesis of both proteins might be responding to the same stimuli. Transferrin gene transcription was increased in both HN and NAR and was unaffected by administration of iron to HN. Transferrin mRNA was not increased in the testis in either HN or NAR, suggesting that augmentation in transferrin gene expression is driven by a non-iron dependent process and is confined to the liver. PMID- 7783404 TI - Direct podocyte damage in the single nephron leads to albuminuria in vivo. AB - The hypothesis that detachment of podocytes leads to albuminuria was tested by studying the single nephron albuminuria in vivo after injecting a saponin solution (0.6 mg/ml) in Bowman's space of superficial glomeruli, which produces selective damage of the podocytes, in female Munich-Wistar-Fromter rats. Animals were subsequently installed under a fluorescence microscope, a purified fluoresceinated rat albumin solution was intravenously injected and the passage of the fluorescent albumin was followed through the microscope. Of the 47 glomeruli injected with the saponin solution (in 6 animals) 46 became fluorescent within seconds with the fluorescence progressing from Bowman's space into the proximal tubule and then in the rest of the tubule. In superficial non-injected and control-injected glomeruli weak fluorescence could be detected only in the glomerular tuft and the peritubular capillaries. Tubuli injected with the saponin solution remained indistinguishable from non-injected tubuli. Electron microscopic study of the saponin-injected glomeruli confirmed the selective removal of podocytes. Immunogold electron microscopy confirmed that the intact albumin molecule effectively passed the glomerular capillary wall at the site where podocyte detachment had occurred. It is concluded that selective removal of podocytes at the single nephron level leads to albuminuria in vivo, and therefore podocytes play a crucial role in regulating the permeability of the glomerular capillary wall. PMID- 7783405 TI - Plasmalogen phospholipid hydrolysis during hypoxic injury of rabbit proximal tubules. AB - We have identified and quantified the major species of arachidonate-containing phospholipids in proximal tubules by high performance liquid chromatographic and gas chromatographic analyses. Arachidonate was found to comprise 53% of the total mass of fatty acids esterified at the sn-2 position of ethanolamine phospholipids, and 51% of that amount resides in three plasmenylethanolamine species containing the vinyl ethers of palmitaldehyde, oleylaldehyde or stearylaldehyde at the sn-1 position. Choline phospholipids contained 21% arachidonylated species and 33% of that amount resides in a single plasmenylcholine species containing the vinyl ether of palmitaldehyde at the sn-1 position. Ten minutes of hypoxia did not cause a significant change in the total phospholipid mass of ethanolamine or choline phospholipids; however, phosphate analysis of the individual phospholipid molecular species containing esterified arachidonic acid in isolated proximal tubules demonstrated a 24% reduction in the mass of the plasmenylethanolamine molecular species with the vinyl ether of oleylaldehyde at the sn-1 position and a 35% reduction in the mass of plasmenylcholine species with palmitaldehyde at the sn-1 position. These studies underscore the pathophysiological importance of plasmalogen phospholipid hydrolysis and suggest that activation of PLA2s, which utilize endogenous proximal tubule plasmalogen substrates, may play an important role in the early generation of arachidonic acid and accompanying phospholipid catabolism during hypoxic cell injury. PMID- 7783406 TI - Ontogeny of angiotensin II type 2 (AT2) receptor mRNA in the rat. AB - To study the distribution of the recently cloned angiotensin II type 2 (AT2) receptor in the rat fetus, a double stranded cDNA was generated by a new and recently described methodology requiring no cloning procedure. The cDNA obtained after reverse transcription (RT) and polymerase chain reaction (PCR) amplification corresponded to 500 base pairs of the gene coding sequence, and included the SP6 and T7 promoters at the 5' and 3' end, respectively. 35S-labeled cRNA sense and antisense probes were synthesized by in vitro transcription and used for in situ hybridization. From 13 to 19 days of gestation the AT2 receptor mRNA expression evolved and extended from a series of paired spots located para axially, which were not identifiable at this level of observation, to a distribution in various mesenchymes (perichondrium, subepidermal layers), muscle cells (tongue, diaphragm, stomach), and classical target organs for Ang II (adrenal gland, kidney, aorta). During the first days after birth, the AT2 receptor mRNA decreased and remained detectable only in the adrenal gland and kidney. The distribution of the AT2 receptor mRNA appeared strikingly different from that of the AT1A receptor, which was studied in parallel for comparison. PMID- 7783407 TI - Renal amino acid transport in adults with oxidative phosphorylation diseases. AB - The clinical manifestations of mitochondrial DNA (mtDNA) mutations depend on a variety of factors including ratios of normal to abnormal mtDNA and tissue specific differences in ATP production by oxidative phosphorylation (OXPHOS). In order to investigate the effects of OXPHOS defects on renal tubule function, we characterized sodium-coupled transport processes in six individuals with OXPHOS diseases. Pathogenic mtDNA mutations were identified in five of these individuals. Sodium coupled transport processes were evaluated by determining fractional excretions of amino acids, glucose, lactate, urate, and phosphate in patients and controls. Four of the six individuals had high fractional excretions of neutral amino acids, indicating abnormal renal tubule reabsorbtion of these amino acids. Abnormalities in fractional excretions of lactate, glucose, urate, and phosphate were less pronounced. These results demonstrate that sodium-coupled transport processes in the kidney are sensitive to OXPHOS impairment. When abnormalities in these processes are encountered, an OXPHOS disease should be included in the differential diagnosis. PMID- 7783408 TI - Glomerular morphometry in childhood reflux nephropathy, emphasizing the capillary changes. AB - As a consequence of nephron loss, reflux nephropathy (RN) causes considerable glomerular hypertrophy. To examine the relative contributions of capillary dilatation and growth in producing hypertrophy, glomeruli contained in unscarred areas of renal biopsies from 19 children with RN were compared with those in 16 children with minimal change nephrotic syndrome and 16 with recurrent hematuria, who were used as controls representing normal childhood growth. Using computerized digitometry we measured the mean glomerular tuft area (GTA) in all complete, undistorted, nonsclerotic glomeruli in periodic acid-Schiff (PAS) stains. Measurements were repeated in four glomeruli of uniform size in periodic acid-silver methenamine stains, the results (GTA4) correlating significantly with GTA. In the same four glomeruli we measured the mean individual capillary luminal area (CLA) and counted the mean number of lumens per glomerulus (N). Mean mesangial area (MA) was calculated as GTA4 - (CLA x N). Cells per distal mesangial region were counted in PAS stains. GTA, GTA4, N, MA and mesangial cell counts were significantly greater in RN than controls, but CLA and fractional MA (MA/GTA%) did not differ. N correlated highly significantly with GTA4 in both RN and controls, but CLA did not do so. These findings are consistent with capillary growth by subdivision being the main mechanism of glomerular hypertrophy when nephron loss occurs during childhood, and the identity of the regressions of N versus GTA4 in RN and controls suggests that compensatory hypertrophy resembles the normal glomerular growth pattern in this age group. PMID- 7783410 TI - A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group. AB - A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783409 TI - Renal ischemia/reperfusion injury contributes to renal damage in experimental anti-myeloperoxidase-associated proliferative glomerulonephritis. AB - The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the present study we investigated the contribution of renal ischemia to the induction of anti myeloperoxidase (MPO) associated NCGN in a previously described rat model of this disease. The development of renal lesions is dependent on the presence of an anti MPO immune response and the localization of a lysosomal extract containing lytic enzymes and MPO in combination with hydrogen peroxide (H2O2) along the glomerular basement membrane (GBM). The hypothesis tested whether perfusion of hydrogen peroxide (H2O2) could be replaced by ischemia/reperfusion (I/R) injury, as I/R injury activates endothelial cells to produce oxygen metabolites. I/R was induced by clamping the renal artery for 20 minutes in kidneys in which the circulation had been restored several minutes after perfusion with the lysosomal extract in MPO immunized rats. Rats developed lesions characterized by intra- and extracapillary cell proliferation, periglomerular infiltration, ruptures in Bowman's capsule, ischemic tubuli, and interstitial mononuclear infiltrate. Immune deposits, however, persisted for a longer time along the GBM after perfusion of lytic enzymes followed by I/R injury compared to previous studies in which H2O2 in conjunction with lytic enzymes were perfused in MPO-immunized rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783411 TI - Racial differences in renal allograft survival: the role of systemic hypertension. AB - The rate of decline in the number of functioning renal allografts beyond the first year after transplantation has changed little in the last 25 years, and during long-term follow-up most allografts are lost due to chronic transplant rejection or patient death. The recipient race correlates with allograft survival, and African American recipients have a lower allograft survival than Caucasians. The goal of the present study was to identify clinical variables present during the first six months after transplantation that predict the loss of renal allografts beyond six months after transplantation, and in particular to determine the role of systemic hypertension on renal allograft survival in black and white recipients. This study includes 547 recipients of first cadaveric renal allografts performed at The Ohio State University. All patients were treated with a uniform immunosuppressive protocol and had a follow-up of at least three years. By multivariate analysis the following variables correlate with poor allograft survival: an elevated serum creatinine concentration measured six months after transplantation (SCr6mo) (P < 0.0001); black race (P < 0.0001); increasing numbers of acute rejection episodes (ATR) (P = 0.002); and young recipients (P = 0.026). Allograft survival is significantly worse in black (mean allograft half life of 7.7 +/- 1.3 years) than in white recipients (24 +/- 3 years) (P < 0.0001). Black recipients also have a significantly higher six month average mean arterial blood pressure (MAP) (105 +/- 8 mm Hg) than white recipients (102 +/- 7 mm Hg) (P = 0.002). However, the prevalence of hypertension is not significantly different in black (33%) than in white recipients (26%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783412 TI - Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. AB - Alport syndrome (AS) is an hereditary disease of basement membrane collagen. It is mainly transmitted as a dominant X-linked trait and caused by mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen. However, autosomal recessive AS due to mutations in the COL4A3 or COL4A4 genes could represent up to 15% of AS. Using the immunofluorescence technique, we analyzed the distribution of the different chains of type IV collagen in renal (12 specimens) and skin (4 specimens) basement membranes of 12 AS patients belonging to 11 unrelated kindreds in which autosomal recessive inheritance had been demonstrated (3 kindreds) or was suggested by clinical and genealogic data (8 kindreds). The renal and skin distribution was normal in one patient with COL4A4 mutations. A peculiar pattern of distribution of the alpha 3-alpha 5(IV) chains was observed in the other patients. It was characterized the co-absence of the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains in the glomerular basement membrane, and the presence of the alpha 5(IV) chain in a series of extraglomerular basement membranes including capsular, collecting ducts and epidermal basement membranes, a combination never observed in X-linked AS. This immunohistochemical pattern is correlated with the specific distribution of the alpha 3-alpha 5 chains of type IV collagen chains within extraglomerular basement membranes. It could be a useful marker for the identification of autosomal recessive AS. PMID- 7783413 TI - Treatment of malnourished CAPD patients with an amino acid based dialysate. AB - Nineteen malnourished chronic peritoneal dialysis patients who were ingesting a low protein intake underwent metabolic balance studies to test whether a dialysate that contained amino acids would improve their protein nutrition. Patients lived in the hospital for 35 days while they ate a constant diet and underwent their usual regimen of continuous ambulatory peritoneal dialysis (CAPD). The first 15 days served as a Baseline Phase. For the last 20 days, the usual dialysate was substituted with a dialysate of essentially the same composition except that it contained 1.1% essential and nonessential amino acids and no glucose. Patients received one or two dialysate exchanges with amino acids each day depending on the amount necessary to bring the individual's dietary protein plus dialysate amino acid intake to 1.1 to 1.3 g/kg body weight/day. During Baseline, patients were in neutral nitrogen balance; net protein anabolism was positive, as determined from 15N-glycine studies. After commencing intraperitoneal amino acid therapy, nitrogen balance became significantly positive, there was a significant increase in net protein anabolism, the fasting morning plasma amino acid pattern became more normal, and serum total protein and transferrin concentrations rose. Patients generally tolerated the treatment well, although some patients developed mild metabolic acidemia. These findings indicate that a dialysate containing amino acids may improve protein malnutrition in CAPD patients ingesting low protein intakes. PMID- 7783414 TI - Impaired endotoxin-induced interleukin-1 beta secretion, not total production, of mononuclear cells from ESRD patients. AB - Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS induced IL-1 beta production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1 beta secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1 beta production remained unchanged but IL-1 beta secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1 beta secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1 beta secretion (P < 0.01) but did not enhance total IL 1 beta production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNF alpha was different comparing the three study groups. We conclude that LPS-induced IL-1 beta secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1 beta, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1 beta secretion in the presence of unchanged total IL-1 beta production. We speculate that PGE2 could inactivate the IL-1 beta converting enzyme which is essential for processing and secretion of mature IL-1 beta. PMID- 7783415 TI - Long-term thromboxane-synthase inhibition prolongs survival in murine lupus nephritis. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by nephritis, in which mortality is largely influenced by the severity of renal involvement. As there are evidences that thromboxane (TX)A2 plays an important role in the pathogenesis of lupus nephritis, we decided to assess the effects of long-term suppression of TXA2 synthesis on the progression of the disease, by designing a study of TXA2-synthase inhibition having adequate size to detect an effect on mortality as the primary end-point. Thus, we randomized 362 NZBxNZW mice (11-week-old at entry) to one of the following treatments: a TXA2 synthase inhibitor, FCE 22178 (300 mg/kg daily), saline or cyclophosphamide (5 mg/mouse weekly x 4 weeks) used as reference treatment. The TXA2 synthase inhibitor suppressed TXA2 biosynthesis, as reflected by urinary TXB2 and 2,3-dinor-TXB2 excretion (by 78% and 90%, respectively) and significantly reduced mortality (death rate: 34% vs. 61% in controls, at 37 weeks, P < 0.01). A significant reduction in proteinuria (9 +/- 1.6 vs. 17.3 +/- 2.4 mg/24 hr in FCE 22178 vs. saline, P < 0.01) and glomerular lesions was observed up to 30 weeks but not at 37 weeks. In contrast, cyclophosphamide prevented the development of proteinuria and histologic lesions, and reduced mortality to 8% at 37 weeks. Renal plasma flow and glomerular filtration rate were lower (by 29% and 52%, respectively) in 37-week-old as compared to young NZBxNZW mice. These parameters were further depressed by cyclophosphamide (by 48% and 45% vs. age-matched controls, respectively, P < 0.01) but were not altered significantly by FCE 22178.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783416 TI - Association of ACE gene polymorphism and diabetic nephropathy? The Diabetic Nephropathy Study Group. AB - In patients with type 1 diabetes an association has been found between an insertion/deletion (I/D) polymorphism in the gene for angiotensin I converting enzyme and the presence of diabetic nephropathy. Our objective was (i) to assess this association in a large cohort of patients with type 1 diabetes and (ii) to examine whether this finding also applies to type 2 diabetes. We examined 247 patients with type 1 diabetes of more than 10 years duration (135 patients > or = 20 years): Nephropathy was present in 114 and absent in 133 patients. Furthermore we separately analyzed 455 patients with type 2 diabetes of more than 10 years duration (158 patients > or = 20 years). Nephropathy was present in 247 and absent in 208 patients. Nephropathy was defined by confirmed presence of albuminuria > 30 mg/day (or > 20 micrograms/min). The I/D polymorphism was analyzed with PCR technique and alleles were visualized on 2% agarose gels after ethidium staining. Allele frequencies in the overall diabetic population did not differ significantly from the normal population. Distribution of genotypes was not significantly different between type 1 patients with and without nephropathy (P = 0.377). Also, no significant difference in genotype distribution was found between type 2 diabetic patients with and without nephropathy (P = 0.948). We conclude that no significant association between I/D polymorphism and nephropathy was demonstrable in either type 1 or type 2 diabetes, despite considerable statistical power of the patient sample and adequate duration of diabetes for nephropathy to become manifest. PMID- 7783417 TI - Down-regulation of PTH-PTHrP receptor of heart in CRF: role of [Ca2+]i. AB - The mRNA of PTH-PTHrP receptor in the kidney and liver of CRF rats is down regulated. It is not known whether this is a generalized phenomenon and the signals that mediate such down-regulation are not evident. Excess PTH in CRF induces a rise in basal levels of cytosolic calcium ([Ca2+]i), and the high [Ca2+]i is implicated in the genesis of cell dysfunction in CRF. Therefore, it is reasonable to propose that the PTH-induced rise in [Ca2+]i provides a negative feedback control system for the down-regulation of the mRNA of the PTH-PTHrP in order to protect the cells from the harmful effects of progressive rise in blood levels of PTH in CRF. The heart contains the mRNA for this receptor and it is a target organ for PTH action. We examined whether the message of the PTH-PTHrP receptor is down-regulated in the heart of CRF animals and evaluated the role of [Ca2+]i in this process. The expression of the mRNA of the PTH-PTHrP was significantly reduced in the heart of CRF rats as compared to normal animals. Also, the CRF rats had elevated blood levels of PTH and high [Ca2+]i of cardiac myocytes. The parathyroidectomy of CRF rats prevented the rise in blood PTH levels and normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels. The treatment of CRF rats with verapamil normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels, despite marked elevation of blood levels of PTH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783418 TI - Assessing the peritoneal dialysis capacities of individual patients. AB - A method for measuring the peritoneal dialysis capacity (PDC) of the individual patient has been developed as an aid to treatment of patients with renal failure and peritoneal dialysis. The patient collects the data him or herself during an almost normal CAPD day using a carefully designed protocol whereby the nursing time is kept to a minimum. The three-pore model is used to describe the PDC with three physiological parameters: (1.) the 'Area' parameter (A0/delta X), which determines the diffusion of small solutes and the hydraulic conductance of the membrane (LpS); (2.) the final reabsorption rate of fluid from the abdominal cavity to blood (JVAR) when the glucose gradient has dissipated; and (3.) the large pore fluid flux (of plasma, JVL), which determines the loss of protein to the PD fluid. In the adult PD population (age 60, N = 97) the normal 'Area' parameter was 23,600 cm/1.73 m2, with an SEM of 650. The JVAR was 1.49 ml/min/1.73 m2 and JVL was 0.078 ml/min/1.73 m2. The PDC parameters were reproducible and could adequately predict the concentrations of the test solutes as well as that of beta 2-microglobulin. The results in terms of clearance, 'UF volume' and nutritional consequences were presented on easily understandable graphs, whereby patient compliance was improved. These physiological parameters are highly dynamic, as evidenced by the marked increases observed during peritonitis. It seems safe to conclude that PDC is a useful tool to achieve adequate dialysis and to enhance the understanding of PD exchange. PMID- 7783419 TI - A COL4A3 gene mutation and post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. AB - The X-linked Alport syndrome is associated with mutations and deletions in COL4A5 gene, one of six genes which constitute the alpha-chains of type IV collagen in basement membranes. The autosomal recessive form of Alport syndrome is characterized by mutations and deletions in the COL4A3 and COL4A4 genes. A fraction of Alport patients who undergo renal transplantation develop anti glomerular basement membrane (GBM) nephritis, which results in loss of the renal allograft function. Recently, the target for alloantibodies from an X-linked Alport patient with complete COL4A5 gene deletion was determined to be the alpha 3 chain of type IV collagen. The present study characterized the post-transplant alloantibodies from an autosomal recessive Alport patient with anti-GBM glomerulonephritis and a COL4A3 gene mutation which predicted a loss of 85% of the alpha 3(IV) NC1 domain. The specificity of these new antibodies were studied using glomerular basement membrane constituents and recombinant type IV collagen domains. The results establish the target for the alloantibodies from an autosomal recessive Alport patient with COL4A3 deletion as principally the alpha 3(IV) collagen chain, similar to the post-transplant alloantibodies from X-linked Alport patients with COL4A5 gene deletions. The absence of alpha 3(IV) chain in the GBM of patients with both these forms of Alport syndrome, due either to a failure of synthesis or a failure of assembly, presumably leads to a loss of immunologic tolerance for the alpha 3(IV) NC1 domain in transplanted allografts. PMID- 7783420 TI - Trade-offs in the adaptation to acidosis. PMID- 7783421 TI - Interleukin-12. Biologic activity, therapeutic utility, and role in disease. AB - IL-12 is a heterodimeric cytokine that promotes cell-mediated immunity through its regulatory effects on T and NK cells. In some murine infectious disease models, IL-12 was shown to be produced endogenously in response to infection, and the exogenous administration of IL-12 to mice with either infectious diseases or tumors has resulted in significant therapeutic effects. IL-12 was protective early in the disease process, as well as against established disease. However, the biologic activities of IL-12 that are beneficial in the host response to these infectious diseases and malignancies can also be deleterious in certain disease states. Thus, IL-12 has considerable potential for the treatment of a variety of human disorders if used under the appropriate conditions. Likewise, antagonists of IL-12 may have a role in controlling diseases with pathologies that are mediated through immune mechanisms. PMID- 7783422 TI - Down-regulation of the IGF-1 system parallels the attenuation in the proliferative capacity of rat ventricular myocytes during postnatal development. AB - BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R) and its ligand (IGF-1) have been implicated in the growth of several cell types, including ventricular myocytes. However, the growth-promoting effect of this pathway on myocyte hypertrophy and hyperplasia has not been determined. During early postnatal development, myocyte cell volume increases nearly 25-fold, and myocyte proliferation is markedly attenuated, so a progressive decrease in this signaling mechanism will indicate that the IGF-1-IGF-1R system is mostly involved in cell proliferation. Conversely, a continuous increase in the expression of IGF-1 and IGF-1R in myocytes with maturation will suggest its involvement in cellular hypertrophy. DESIGN: Myocytes were isolated from fetal rats and from rats at 1, 5, 11, 21, 35, and 60 days of age. Total RNA was extracted from these cells, and the expression of IGF-1, IGF-2, IGF-1R, and DNA polymerase alpha was measured by reverse transcriptase-PCR. IGF-1R mRNA levels were also determined by RNase protection assay, and the changes in IGF-1R protein were determined by the cross linking technique. Finally, the expression of late growth-related genes was determined and compared with the fraction of muscle cells synthesizing DNA. These analyses were restricted to the left ventricular free wall and septum combined. RESULTS: Myocardial development was characterized by a progressive decrease in the expression of late growth-related genes in myocytes, which was particularly evident at 21 days after birth and persisted up to 2 months of age. The expression of IGF-2 in these cells decreased at birth, whereas the attenuation in IGF-1 mRNA became apparent a few days later during postnatal development. The induction of IGF-1R at the message and protein levels decreased by 11 days, and this phenomenon was more evident at the subsequent age intervals. Moreover, DNA synthesis in myocytes was sharply reduced at 21 days after birth. CONCLUSIONS: In conclusion, the decline in myocyte proliferation with cardiac development appears to be coupled with attenuation of the IGF-1-IGF-1R system, which may condition the changes in late growth-regulated genes, DNA replication, and cellular mitotic division in the myocardium. PMID- 7783423 TI - Use of differential display to identify differentially expressed mRNAs induced by rat carotid artery balloon angioplasty. AB - BACKGROUND: We have used differential display technology in an animal model of arterial restenosis to study the molecular mechanisms of neointima formation. EXPERIMENTAL DESIGN: Balloon angioplasty of the rat common carotid artery was performed, and tissues were examined from naive animals (control) and from animals that had undergone angioplasty 6 hours, 3 days, and 14 days earlier. Total RNA was isolated, and differential display was performed to identify mRNA transcripts whose expression is modulated in a temporal fashion as a consequence of balloon angioplasty. RESULTS: Using total RNA isolated from vessels excised from naive rats and those from rats that underwent angioplasty up to 14 days earlier, we describe two differentially regulated transcripts by differential display and verify the expression pattern of these same transcripts by Northern analysis. DNA sequence analysis has identified one of these angioplasty-induced transcripts as a novel sequence and the other as the tryptophan hydroxylase and protein kinase C regulatory protein 14-3-3 gamma. CONCLUSIONS: In this study, we describe the in vivo application of the differential display technique in a rat carotid artery angioplasty model to identify mRNA transcripts whose expression is modulated selectively in vessels undergoing neointima formation. Use of this technique in animal models of disease should facilitate our understanding of gene expression patterns in pathogenesis and may serve as a reliable technique to "fingerprint" disease processes. PMID- 7783425 TI - Transforming growth factor-beta 1 and collagen gene expression during postnatal skin development and fibrosis in the tight-skin mouse. AB - BACKGROUND: The tight-skin (Tsk) mutation in the mouse leads to widespread connective tissue abnormalities characterized by excessive collagen deposition that is similar to that observed in human scleroderma. Heterozygous mice develop skin fibrosis shortly after birth, providing a valuable model to investigate the sequence of events leading to fibrosis. EXPERIMENTAL DESIGN: We have studied by in situ RNA hybridization the expression of procollagen alpha 1(I), alpha 1(III), alpha 2(VI) and transforming growth factor-beta 1 (TGF-beta 1) genes in the skin of Tsk mutant and normal newborn to aged mice. Tsk and normal skin sections at each age were mounted on the same slide to ensure identical experimental conditions, allowing for comparative analyses. RESULTS: All genes are under temporospatial regulation and exhibit characteristic patterns of expression during postnatal skin growth and development. TGF-beta 1 mRNA is detected in fibroblasts only during the rapid postnatal growth of the skin in parallel with high collagen I, III, and VI gene expression. Collagen I and III gene-expressing fibroblasts are observed in excess in the Tsk fibrotic lesions. An abnormal pattern of collagen VI expression is only observed at later stages in the fibrotic process. Collagen VI shows a different expression pattern in both normal skin development and fibrosis, suggesting noncoordinate regulation with collagen I and III genes. CONCLUSIONS: The fibrotic process in Tsk mice results from the persistence of high collagen I and III expression by a subpopulation of fibroblasts. Collagen VI overexpression participates later in the fibrotic process. In contrast with human scleroderma and other skin fibrotic diseases, TGF beta 1 mRNA is not detected in the areas of abnormal collagen expression and fibrosis of Tsk. Alternative pathways should be explored to understand the abnormal extracellular matrix deposition of Tsk fibroblasts. PMID- 7783424 TI - Differential expression of the versican and decorin genes in photoaged and sun protected skin. Comparison by immunohistochemical and northern analyses. AB - BACKGROUND: Chronic sun exposure induces numerous changes in exposed skin; the most striking histopathologic change is the massive accumulation of material with the staining characteristics of elastin, termed solar elastosis, in the superficial dermis. Previous studies have identified elastic fibers within areas of solar elastosis, as well as a decrease in collagen content. Recently, the large chondroitin sulfate (CS) proteoglycan, versican, has been identified in the dermis in association with elastic fibers, and the smaller CS proteoglycan, decorin, has been shown to codistribute with collagen fibers. Thus, changes in expression of these CS proteoglycans might be expected in photoaging and may help to explain the clinical alterations of chronically sun-exposed skin. EXPERIMENTAL DESIGN: Immunohistochemical staining and confocal laser scanning microscopy for versican and decorin was performed on paired tissue samples from photoaged and non-sun-exposed skin taken from the same individuals. To investigate versican and decorin mRNA expression, Northern analysis was performed on paired fibroblast cultures derived from tissue explants of photoaged and non-sun-exposed skin. RESULTS: Immunohistochemical staining and confocal laser scanning microscopy revealed a massive accumulation of versican localized to the abnormally large fibers comprising solar elastosis in the superficial and mid-dermis of photoaged specimens. Decorin staining was greatly decreased within the area of solar elastosis. Similarly, changes in mRNA were measured from fibroblast cultures, with a significant increase in versican mRNA in cultures derived from photoaged skin, whereas decorin mRNA levels were significantly decreased in photoaged skin. CONCLUSIONS: This study provides further evidence for the close association of versican with elastic fibers and decorin with collagen fibers, even in the situation of abnormal fiber deposition occurring in photodamaged skin. In addition, changes in versican and decorin immunostaining are accompanied by similar alterations in gene expression. PMID- 7783426 TI - Immunophenotypic and immunoelectron microscopic characterization of major constituent cells in malignant fibrous histiocytoma using human cell lines and their transplanted tumors in immunodeficient mice. AB - BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life. Its histogenesis, however, is still a matter of debate because of its various cellular components. EXPERIMENTAL DESIGN: To elucidate the nature of tumor cells of MFH, six human MFH cell lines were compared immunohistochemically and immunoelectron microscopically with fibrosarcoma and fibroblast cell lines. In vitro differentiation of tumor cells was evaluated after the treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, macrophage CSF, and granulocyte-macrophage CSF. Heterotransplantation of MFH tumor cells into nude mice and severe combined immunodeficient mice was performed to examine whether the tumor cells differentiate toward histiocytes or not. Gene expression of monocyte chemoattractant protein-1 in cultured tumor cells and transplanted tumors was also evaluated. RESULTS: All MFH cell lines examined were positive for collagen type I and prolyl hydroxylase. They failed to react with most anti-myeloid mAb such as CD11c, CD14, CD15, CD33, CD35, CD45, anti-HLA-DR, and PM-2K. Several Ab, including CD13, CD32, CD68, CD71, and HAM56, were reactive with MFH cells. However, all of these Ab were also reactive with fibrosarcoma and/or fibroblastic cell lines. These data indicate that MFH cell lines possess immunophenotypic characteristics very similar to those of fibrosarcoma and fibroblastic cell lines. In vitro treatment of tumor cells with TPA, IL-3, macrophage CSF, granulocyte-macrophage CSF, or their combination did not change their immunophenotypic characteristics and did not induce differentiation toward histiocytes (macrophages). Transplantation of tumor cells into nude mice and severe combined immunodeficient mice produced tumors similar in histology to human MFH. Tumor cells in the transplanted tumors revealed the same immunophenotypic characterization that they did in vitro. No in vivo differentiation of tumor cells toward histiocytes was observed. Immunohistochemical staining with anti-mouse macrophage mAb revealed marked infiltration of macrophages of mouse origin. Quantitative immunoelectron microscopy disclosed that these cells coincided with histiocyte-like cells. Gene expression of monocyte chemoattractant protein-1 was detected in all MFH cell lines as well as in transplanted tumors. CONCLUSIONS: The histiocyte-like cells in malignant fibrous histiocytoma are not a neoplastic component but rather infiltrated macrophages attracted by tumor-derived monocyte chemoattractant(s), and the tumor cells belong to a fibroblastic lineage differentiated from mesenchymal cells. PMID- 7783427 TI - Bovine melanoma growth stimulatory activity: a new monocyte-macrophage-derived cytokine of the IL-8 family. Partial structure, function, and expression in acute pulmonary inflammation. AB - BACKGROUND: Neutrophil-chemotactic peptides are a family of small basic peptides 70 to 80 amino acids in length. They contain four conserved cysteine residues, the first two spaced by one amino acid (C-X-C). The best characterized species is human IL-8. Other prominent members are melanoma growth stimulatory activity (GRO alpha), neutrophil-activating peptide-2, and epithelial-cell derived neutrophil activating protein 78. EXPERIMENTAL DESIGN: Bovine monocytes and alveolar macrophages were induced by lipopolysaccaride, and a major neutrophil chemotactic activity in the supernatant was purified by cation-exchange chromatography and reversed-phase HPLC. The chemotaxin was then analyzed for biologic activity on bovine neutrophils by in vitro chemotaxis, shape change, and transient rise of intracellular-free calcium concentration. The in vivo role of bovine GRO (boGRO) was tested immunohistologically in confirmed cases of pneumonic pasteurellosis. RESULTS: We have purified and partially sequenced a bovine homologue of human GRO alpha. The partial amino acid sequence of boGRO was: APVVNELRCQCLQTLQGIHLKNIQSVKVTTPGP. BoGRO was biologically active and induced a dose-dependent neutrophil migration in the range of 10(-7) to 10(-9) M. BoGRO also induced a dose-dependent shape change in bovine neutrophils similar to human IL-8. This effect was detectable down to 10(-10) M. Similar effects were observed on the transient rise of intracellular-free calcium concentration. In bovine pneumonic pasteurellosis and, to a lesser extent, in normal lungs, immunoreactivity to human GRO was highly positive in hypertrophic type-II epithelial cells and in mesothelial cells, whereas pleural fibroblasts and bronchial epithelial cells were negative. CONCLUSIONS: BoGRO is a prominent neutrophil chemoattractant secreted by monocytes and alveolar macrophages. It is active at similar concentrations as human IL-8. The strong immunoreactivity in type-II epithelial and mesothelial cells of bovine pneumonia strongly suggest a role for boGRO in the genesis of pulmonary inflammation. PMID- 7783428 TI - The role of macrophage colony-stimulating factor in the differentiation and proliferation of Kupffer cells in the liver of protein-deprived mice. AB - BACKGROUND: Protein calorie malnutrition is known to induce various macrophage dysfunctions, such as the impairment of their phagocytic function, proliferative capacity, and bactericidal activity. However, little is known about the behavior of Kupffer cells under protein calorie malnutrition in vivo. EXPERIMENTAL DESIGN: To investigate the behavior of Kupffer cells under protein calorie malnutrition, we fed mice on a low protein (protein-derived) diet for 4 weeks and examined the number, cytologic changes, and proliferative capacity of their Kupffer cells. To detect macrophage precursor cells, colony-forming assays were performed in the bone marrow, spleen, and liver of the mice. To investigate the relationship of Kupffer cells to CSF, the serum levels of IL-6 and granulocyte-macrophage colony stimulating factor were measured by ELISA, and the expression of macrophage colony-stimulating factor (M-CSF) mRNA in the liver was determined by Northern blot analysis. The recovery processes of Kupffer cells in the protein-deprived mice after normal protein feeding or daily recombinant human macrophage colony stimulating factor administration were also investigated. RESULTS: In the protein deprived mice, Kupffer cells decreased in number to two-thirds that of the normally fed (nondeprived) mice, showed the cytologic and ultrastructural features of maturation failure, and had reduced proliferative capacity. After normal protein feeding or recombinant human macrophage colony-stimulating factor administration, the number, morphology, and proliferative capacity of the Kupffer cells in the liver returned to normal, and they matured as in the nondeprived mice. In the protein-deprived mice, the serum levels of IL-6 and granulocyte macrophage colony-stimulating factor increased, and the expression of M-CSF mRNA in the liver was reduced. In the bone marrow, the granulocyte-macrophage colony forming cells and macrophage colony-forming cells were increased, and the influx of monocytes into the liver was temporarily enhanced; however, the number of monocytes in the peripheral blood was decreased. CONCLUSIONS: These results suggest that the reduced production of M-CSF in the liver of protein-deprived mice results in numerical reduction, maturation failure, and decreased proliferative capacity of Kupffer cells. PMID- 7783429 TI - Laminin abnormality in severe childhood autosomal recessive muscular dystrophy. AB - BACKGROUND: In skeletal muscle, dystrophin exists in a large oligomeric complex tightly associated with several novel sarcolemmal proteins, including the 50-kDa transmembrane glycoprotein called adhalin. The dystrophin-glycoprotein complex links the subsarcolemmal actin cytoskeleton to the basal lamina component laminin, thus providing stability to the sarcolemma. Disturbance of this linkage due to the absence of dystrophin plays a crucial role in the molecular pathogenesis of muscle fiber necrosis in Duchenne muscular dystrophy. Severe childhood autosomal recessive muscular dystrophy (SCARMD) is similar to Duchenne muscular dystrophy in phenotype but is characterized by the deficiency of adhalin. At present, the status of the link between the dystrophin-glycoprotein complex and laminin is unclear in SCARMD. EXPERIMENTAL DESIGN: We investigated, by immunohistochemistry using confocal laser scanning microscopy, the status of the expression of laminin subunits, A, M, B1, B2, and S chains, in skeletal muscle biopsy specimens of eight SCARMD patients from various human populations. In addition, we correlated the severity of laminin abnormality with the severity of both clinical symptoms and histopathologic changes in these patients. RESULTS: The reduction of laminin B1 chain and the overexpression of the S chain, a homologue of B1, in the extrajunctional basal lamina were observed in the five patients who had advanced clinical symptoms and histopathologic changes. Abnormalities in the expression of laminin were not observed in the three less affected patients. CONCLUSIONS: The expression of laminin is greatly disturbed in severely diseased SCARMD muscle deficient in adhalin. Disturbance of sarcolemma basal lamina interaction may play an important role in the molecular pathogenesis of muscle fiber necrosis in SCARMD. PMID- 7783430 TI - Liver and kidney necrosis in selenium-deficient rats depleted of glutathione. AB - BACKGROUND: Selenium and glutathione have interrelated oxidant defense roles in vivo. Experiments were carried out to determine the effect of glutathione depletion in selenium-deficient rats. EXPERIMENTAL DESIGN: Selenium-deficient and control rats were injected with phorone to deplete glutathione. Histologic assessment of liver and kidney injury was performed at 24 hours. In another experiment, glutathione depletion, lipid peroxidation, and liver injury were measured for 12 hours after phorone administration to determine their relationships with one another. In a final experiment, selenoproteins were correlated with protection against lipid peroxidation and liver necrosis. Selenium-deficient rats were injected with vehicle alone and with 5, 10, or 25 micrograms of selenium/kg. Twelve hours later, selenoproteins were measured in some of the rats, and phorone was injected into others. Liver injury and lipid peroxidation were assessed 6 hours after the phorone injection. RESULTS: Twenty four hours after phorone administration (125 mg/kg), centrilobular hepatic necrosis and renal tubular necrosis were evident in selenium-deficient rats but not in controls. The time-course experiment revealed that phorone (250 mg/kg) caused sharp decreases in liver and kidney glutathione levels in both groups within 2 to 4 hours. Lipid peroxidation, as assessed by F2 isoprostane concentrations, in selenium-deficient animals. Liver necrosis, indicated by a rise in plasma ALT, took place in selenium-deficient rats but not in controls. Selenium injections into selenium-deficient rats increased selenoprotein P concentrations from 4% of control to as high as 39% but had little effect on glutathione peroxidase activities. Six hours after phorone administration, rats that had received selenium had no rise in ALT, and the rises in F2 isoprostanes were abolished or attenuated. CONCLUSIONS: We conclude that depletion of glutathione in selenium-deficient liver and kidney leads to necrosis in those organs associated with evidence of lipid peroxidation. Protection against this injury by selenium correlates with selenoprotein P concentration in plasma but not with glutathione peroxidase activity in tissues or in plasma. These findings raise the possibility that selenoprotein P protects cell membranes against oxidant injury and that glutathione is involved in that protection. PMID- 7783431 TI - Heterogeneous hepatocellular expression of glutamine synthetase in developing mouse liver and in testicular transplants of fetal liver. AB - BACKGROUND: Glutamine synthetase is exclusively expressed in pericentral hepatocytes in mammalian liver, but its regulation mechanism is still largely unknown. EXPERIMENTAL DESIGN: Heterogeneous expression of glutamine synthetase was examined in detail during mouse liver development by immunohistochemistry and by in situ hybridization. Heterogeneous expression of this enzyme was also analyzed in immature liver fragments transplanted to an ectopic site where no portal blood flow exists. RESULTS: At 18.5 days of gestation, a random, spotty distribution of low levels of glutamine synthetase mRNA was observed all over the liver parenchyma, but the enzyme protein was not detectable immunohistochemically in the liver at any fetal stage. Glutamine synthetase and its mRNA began to be heterogeneously expressed in pericentral hepatocytes 2 to 3 days after birth, when glycogen accumulation in the liver parenchyma was rather homogeneous. In the early postnatal development, a mosaic distribution of positive and negative hepatocytes with respect to glutamine synthetase protein and mRNA was noted around the central veins. Subsequently, mRNA distribution gradually became continuous, although some hepatocytes still lacked protein, indicating partial regulation at the translational level. When fetal liver fragments that had not yet heterogeneously expressed glutamine synthetase were cultured under the testis capsule of male mice, only pericentral hepatocytes expressed this enzyme after 2 months. However, the distribution of glutamine synthetase protein- and mRNA positive hepatocytes around the central veins was patchy rather than continuous, as in perinatal livers. CONCLUSIONS: These results support the importance of local interactions of hepatocytes with intrahepatic cell populations and/or structural elements. Furthermore, they demonstrate that the capacity for the positional expression of glutamine synthetase is already established at a fetal age before expression of glutamine synthetase can be detected. PMID- 7783432 TI - Vascular endothelium-derived cells containing smooth muscle actin are present in restenosis. PMID- 7783433 TI - Percutaneous biopsy of abdominal organs under ultrasound guidance. AB - Percutaneous sampling of one or more abdominal organs was performed under ultrasound guidance in 89 dogs and 16 cats. Tissue core samples were considered to be of diagnostic quality in 92 per cent of hepatic and 100 per cent of renal biopsies. Core biopsies were collected from the prostate in only three cases but each was adjudged of diagnostic quality. The technique allowed a definitive diagnosis or normal tissue to be confirmed in 65 per cent of animals undergoing hepatic biopsy, 83 per cent undergoing renal biopsy and 82 per cent undergoing prostatic biopsy or aspiration. Few complications occurred which could be ascribed with certainty to the procedure. One dog with extensive hepatic necrosis died one week after the biopsy, but necropsy examination was denied. One severely debilitated cat did not recover from general anaesthesia. One dog underwent aspiration of a sterile intraprostatic cyst, and developed prostatic abscessation one week later; prostatic carcinoma was subsequently found. Careful selection and preparation of patients for biopsy are essential. With this caveat, ultrasound guided sampling of abdominal organs is a useful technique allowing a definitive diagnosis in a high proportion of cases. The technique is minimally invasive and the complication rate low. PMID- 7783434 TI - [What is your diagnosis? Paraprostatic cyst in a dog]. PMID- 7783436 TI - Canine eosinophilic folliculitis and furunculosis in three cases. AB - The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined. PMID- 7783435 TI - Vitamin K-dependent coagulopathy in a British Devon rex cat. AB - Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting times were normalised by oral administration of vitamin K. This report confirms the existence of this bleeding disorder in a Devon rex cat in the United Kingdom. PMID- 7783437 TI - Fracture associated sarcoma in the cat. AB - A nine-year-old neutered male cat developed an osteosarcoma 15 months after the surgical repair of the proximal femur using an intramedullary pin at the fracture site. The repair had been effective with good healing of the fracture and restoration of normal activity. PMID- 7783438 TI - Neutrophil phagocyte dysfunction in a weimaraner with recurrent infections. AB - A five-and-a-half-month-old male weimaraner with severe recurrent bacterial infections was assessed for immunocompetence. Results revealed a low serum immunoglobulin G concentration and defective neutrophil phagocytosis. PMID- 7783440 TI - Old age is not a disease. PMID- 7783439 TI - Megaoesophagus and glucocorticoid-deficient hypoadrenocorticism in a dog. AB - A seven-year-old German shepherd dog was referred for acute onset regurgitation. Muscle weakness and severe dermatological disease were present. Thoracic radiographs revealed generalised megaoesophagus. Diagnostic testing revealed glucocorticoid deficiency, and rapid resolution of the megaoesophagus followed appropriate supplementation. The dog made a full recovery. Unique features of this case include a transiently positive antinuclear antibody titre and clinical features of myasthenia gravis. PMID- 7783441 TI - Inheritance of histiocytosis in Bernese mountain dogs. AB - One hundred and twenty-seven cases of histiocytosis in Bernese mountain dogs (BMD) were evaluated to determine if the tumour is inherited. Family data ruled out autosomal recessive, autosomal dominant and sex-linked modes of inheritance. The trait was determined to be inherited with a polygenic mode of inheritance. The salient points permitting this conclusion are: pedigrees developed from independently selected propositi link up allowing the tracing of all cases through several generations; multiple cases occur in the same litter; multiple cases have been produced by given dams and sires; there is a higher frequency of the disease among offspring of affected parents when compared to offspring of normal parents that produced histiocytosis and all offspring in the general population of BMDs; the fact that histiocytosis is common in BMDs and rare in eight other breeds and accounts for 25.4 per cent of the 500 tumours studied in this breed. The heritability of this trait was calculated to be 0.298. PMID- 7783442 TI - Comparison of two shampoos for treatment of Malassezia pachydermatis-associated seborrhoeic dermatitis in basset hounds. AB - A randomised-double-blind parallel study compared the clinical and antimicrobial efficacies of a miconazole-chlorhexidine shampoo with a selenium sulphide shampoo for the treatment of seborrhoeic dermatitis associated with Malassezia pachydermatis in 33 basset hounds. All 16 miconazole-chlorhexidine treated hounds and 11 of 17 selenium sulphide treated hounds improved when shampooed at three day intervals for three weeks. The miconazole-chlorhexidine treated hounds showed significantly greater reductions in pruritus (P < 0.01), erythema (P < 0.001), exudation (P < 0.01) and overall severity (P < 0.001), and in counts of M pachydermatis (P < 0.001), total bacteria (P < 0.001) and coagulase-positive staphylococci (P < 0.001), when compared to the selenium sulphide treated group. Improvements in scaling and coat condition did not vary significantly between the two groups. These results indicate that seborrhoeic dermatitis in basset hounds is often associated with elevated cutaneous populations of M pachydermatis and bacteria, and that the miconazole-chlorhexidine shampoo is more effective than the selenium sulphide product for the treatment for this disease. PMID- 7783444 TI - Complementary coding conforms to the primeval comma-less code. AB - The hypothesis that the universal genetic code is adapted to double-strand coding is supported by its remarkable compatibility with the RNY comma-less hypothesis. Coding by a triplet code on a polynucleotide double-strand allows for enciphering of five additional messages with reference to a chosen primary reading frame. Assuming the acceptance of coupled mutations on both strands, the best codon register for two overlapping messages can be inferred. The idea of evolutionarily compatible coding of two proteins by one nucleotide double-strand is extended to complementary coding for one protein in folded, single-stranded RNA. PMID- 7783443 TI - Lymphocyte memory and affinity selection. AB - The persistence of antigen-specific immune memory appears to require the presence of antigen--suggesting that memory may be due to restimulation of "memory" lymphocytes by persisting antigen. Persistence of antigen, in a form capable of stimulating B cell proliferation, on long-lived, follicular dendritic cells of lymphoid tissue is well documented. Existence of an analogous mechanism for T cell memory maintenance is controversial but can not be ruled out. Here we examine the consequences of immune memory maintenance by antigen-specific lymphocyte restimulation, and estimate the duration of memory as a function of model parameters. We show that the competition for restimulation among memory cell populations results in the selection of the clone having the highest overall affinity for the retained antigen. Thus affinity selection, an important attribute of immunity, is a constitutive property of memory maintenance by antigen-specific restimulation. In the case of B cells, affinity selection is predicted to continue to increase antibody affinity even after somatic mutation stops, and thus may be an important component of affinity maturation. Finally, we discuss several other hypotheses proposed to explain immune memory, including T cell stimulation by cross-reactive antigens. PMID- 7783445 TI - Selection, mutations and codon usage in a bacterial model. AB - We present a statistical model of bacterial evolution based on the coupling between codon usage and tRNA abundance. Such a model interprets this aspect of the evolutionary process as a balance between the codon homogenization effect due to mutation process and the improvement of the translation phase due to natural selection. We develop a thermodynamical description of the asymptotic state of the model. The analysis of naturally occurring sequences shows that the effect of natural selection on codon bias affects genes whose products are largely required at maximal growth rate conditions or undergo rapid transient increases. PMID- 7783446 TI - Periodic selection and hitchhiking in a bacterial population. AB - The accumulation of a neutral marker in a bacterial population under balanced growth in a chemostat follows a jagged curve as adaptive variants continuously appear and sweep the population. Such periodic selection curves are simulated in the present work using deterministic equations that, in contrast to previous models, take full account of the stochastic character of the process. The uncertainties due to the appearance time, the survival probability, and the extent of early growth at small numbers are included as stochastic initial conditions for every new variant--adaptive or neutral--that appears. The model is used to calculate the substitution rate via hitchhiking where a neutral or weakly selected mutation is carried along when a new adaptive one takes over the population. The expected ratio for the probabilities of the presence or absence of a weakly selected or counterselected mutation in the population is also calculated. This can be related to the standard result without hitchhiking if the average time between adaptive shifts is interpreted as an effective population size. PMID- 7783447 TI - Quantification of the three point receptor hypothesis of Cheng and Zee-Cheng. AB - The placement of three heteroatoms at the corners of an acute angle triangle was found to correlate roughly with the antineoplastic activity of a wide range of compounds by Cheng & Zee-Cheng (1972, J. Pharm. Sci. 61, 485). Since then the synthetic routes to compounds having a large number of degrees of freedom, as in the 1,4-dihydroxy-5,8-bis([2-(2-hydroethyl)amino]ethyl) amino-9,10 anthracenedione (DHAQ, mitoxantrone) have been discovered. The subsequent high activity of DHAQ vs. numerous cancers has partially verified the worth of the original hypothesis. Quantitative verification of pharmacophoric hypotheses as theories necessitates the use of Popper's risky experiments. These experiences give rise to verification because, unenlightened by the theory undergoing testing, they would predict a result that would refute the theory. Computational chemistry allows such a confirmation through molecular modeling. The molecular force field, MMX, gives confirmation of the theory by showing the riskiness of the synthetic production of DHAQ for the gas phase. The MM+ forcefield in an aqueous medium computation (132 water molecules) shows that the confirmations of DHAQ does not change appreciably from the gas phase. This computation adds a considerable risk. Aquation could significantly change the favorable conformations of the very conformationally free DHAQ molecule. The fact that it does not confirm that the Zee-Cheng and Cheng hypothesis is a strong one. Additionally, a quantitative relationship arises from the new model for the N-O-O atomic placement. This new quantitative relationship further predicts quantitative risky experiments for further verification (falsification). PMID- 7783448 TI - Linear invariants under Jukes' and Cantor's one-parameter model. AB - Linear invariants are random variables with zero expectations under certain assumptions. In this paper, linear invariants under Jukes' and Cantor's one parameter model, both with and without the assumption that nucleotide frequencies are at equilibrium, are studied using the method developed in a previous paper. Phylogenetic linear invariants (random variables that are linear invariants of some but not all trees of the same number of species) for trees with up to seven species are derived and bases of phylogenetic linear invariant spaces for unrooted trees with four, five and six species are presented. All these bases consist of invariants of simple form. The constraints that specify non phylogenetic linear invariants (invariants shared by all trees of the same number of species) are determined. Under the assumption that nucleotide frequencies are at equilibrium, it is found that (i) each five-species tree has 17 independent phylogenetic linear invariants, and for two different trees with five species, there are at least three phylogenetic linear invariants of one tree that are not invariants of the other tree; (ii) each six-species tree has 98 independent phylogenetic linear invariants, and for two different trees of six species there are at least nine independent phylogenetic linear invariants that are not invariants of the other tree; and (iii) each seven-species tree has 482 independent phylogenetic linear invariants. It is also found that the number of independent phylogenetic linear invariants is much larger without the assumption of equilibrium than with it, but the reverse is true for the number of non phylogenetic linear invariants. A class of random variables that are phylogenetic linear invariants with or without the equilibrium assumption is also identified. PMID- 7783449 TI - Deducing protein structures using logic programming: exploiting minimum data of diverse types. AB - The extent to which a protein can be modeled from constraint data depends on the amount and quality of the data. This report quantifies a relationship between the amount of data and the achievable model resolution. In an information-theoretic framework the number of bits of information per residue needed to constrain a solution was calculated. The number of bits provided by different kinds of constraints was estimated from a tetrahedral lattice where all unique molecules of 6, 9, ..., 21 atoms were enumerated. Subsets of these molecules consistent with different constraint sets were then chosen, counted, and the root-mean square distance between them calculated. This provided the desired relations. In a discrete system the number of possible models can be severely limited with relatively few constraints. An expert system that can model a protein from data of different types was built to illustrate the principle and was tested using known proteins as examples. C-alpha resolutions of 5 A are obtainable from 5 bits of information per amino acid and, in principle, from data that could be rapidly collected using standard biophysical techniques. PMID- 7783450 TI - Evolutionary predictions from invariant physical measures of dynamic processes. AB - The invariant physical measure of a dynamic process comprises the information necessary to compute statistical quantities of the system. It allows us to replace time averages over the system's trajectory by integrals over state-space. In particular, it allows us to compute the long-term growth rate of a fluctuating population and hence to make evolutionary predictions. This is explained here using a one-dimensional difference equation. The invariant physical measure reflects three types of selection in this model: K-selection when the resident has a stable equilibrium; r-selection when the resident exhibits complex dynamics; and c-selection, i.e. selection for lower complexity when the resident undergoes large fluctuations. For all three evolutionary scenarios the interaction of the physical measure with the higher moments of the distribution of offspring numbers is crucial. It is also shown how stochastic noise can affect the invariant physical measure and the evolutionary predictions made from it. PMID- 7783451 TI - Variation of multifunctional surface binding proteins--a virulence strategy for group A streptococci? AB - Variation in surface antigens has been well recognized as a mechanism by which pathogenic organisms can avoid elimination and remain as potential pathogens in immunocompetent individuals. A variety of viral and parasitic organisms elude the immune system by varying their surface antigenic structures. Other persistent human pathogens, for example group A streptococci, are associated with cyclic variation in the severity of infections without any major change in their surface antigenic structures. Recent analysis of group A streptococcal proteins, in particular surface M and M-like proteins, has documented the existence of an array of multifunctional surface proteins which have the ability to bind to a variety of normal human plasma proteins, extracellular matrix components and human cells. The ability to change the functional activities of these surface molecules by genetic recombination among members of a closely related M protein supergene family has now been reported. In this paper, the potential importance of generating functional heterogeneity in surface binding proteins of group A streptococcus is discussed. The role of these proteins in enabling an organism to sense its environment and express the appropriate virulence factors is proposed as an explanation for the periodic changes in the frequency and severity of invasive group A streptococcal infections that can occur in the absence of a toxic-shock-like syndrome. PMID- 7783452 TI - Search strategies for applied molecular evolution. AB - A new approach to drug discovery is based on the generation of high diversity libraries of DNA, RNA, peptides or small molecules. Search of such libraries for useful molecules is an optimization problem on high-dimensional molecular fitness landscapes. We utilize a spin-glass-like model, the NK model, to analyze search strategies based on pooling, mutation, recombination and selective hill-climbing. Our results suggest that pooling followed by recombination and/or hill-climbing finds better candidate molecules than pooling alone on most molecular landscapes. Our results point to new experiments to assess the structure of molecular fitness landscapes and improve current models. PMID- 7783453 TI - Therapeutic effects of the blood-activating and stasis-reducing method in 80 cases of coronary heart disease. AB - The pathogenesis and treatment of coronary heart disease (CHD) may vary, whereas the author believes that the disease is due to blood stasis on a fundamental basis of deficiency, and the principle of treatment is activation of blood. Since stasis may lead to deficiency and vice versa, CHD cannot be cured without removal of stasis, and stasis cannot be completely removed without proper correction of deficiency. The basic method for the treatment of CHD is therefore activation of blood for reduction of stasis. At the same time, according to the conditions of individual patients, the methods of replenishing Qi, warming Yang, nourishing Yin, reducing phlegm and subduing Yang should be applied simultaneously to resolve the problem of deficiency. The author treated 80 cases of CHD by the above rationale and found the results satisfactory, i.e., 28 cases (35%) showed marked symptomatic relief, 46 (57.5%) showed symptomatic improvement, while 6 cases (7.5%) failed. The total effective rate was 92.5%. ECG examination indicated 9 cases markedly effective, 27 improved, while 44 cases failed, for a total effective rate of 45%. Blood pressure and blood lipids also showed significant drops (P < 0.001). PMID- 7783454 TI - Clinical observation on 80 children with peptic ulcer treated primarily by traditional Chinese medicine. AB - Using the empirical recipe of Wang Pengfei (a very experienced TCM doctor) as the main treatment, the authors treated 80 children with peptic ulcer by means of promoting blood circulation, removing blood stasis as well as regulating the flow of qi, alleviating pain, tonifying the stomach and reinforcing the spleen. Measures for hemostasis, correction of anemia and other general treatment were also taken. After 8 weeks of treatment, a total effective rate of 92.5% was obtained. PMID- 7783455 TI - Treatment of senile hypertension based on differential diagnosis of syndromes. PMID- 7783456 TI - Effects of the clearing-heat and nourishing-stomach method in the treatment of chronic gastritis with positive Campylobacter pylori. PMID- 7783457 TI - Prospect for study on treatment of AIDS with traditional Chinese medicine. AB - In this paper, studies on single Chinese medicinal herbs, composite prescriptions, and their active principles, which have been used against HIV both in China and abroad, are highlighted; and the results from clinical treatment of 158 HIV infected patients performed by a China-Tanzania Coordinating Group are also reported. Six of the patients displayed seronegative conversion and remained so in the follow-up for 10 to 15 months. The author assumes that the prescriptions and drugs strengthening the patients' resistance could enhance the efficacy of AIDS treatment. PMID- 7783458 TI - Treatment of primary trigeminal neuralgia with acupuncture at the sphenopalatine ganglion. PMID- 7783459 TI - Composite acupuncture treatment of mental retardation in children. AB - 128 children of mental retardation were diagnosed in accordance with the diagnostic standards proposed by WHO in 1985. The patients were treated compositely with acupuncture, auriculo-acupoint pellet pressure and herbal plasters on acupoints, bringing about improved mental developments in intelligence quotient (IQ) and social adaptation behaviour (SAB), as evidenced by recognized intelligence tests for children. PMID- 7783461 TI - Dr. Yang Jiasan's experience in applying the back-shu points. PMID- 7783460 TI - Treatment of chronic prostatitis with laser acupuncture. PMID- 7783462 TI - 78 cases of periomarthritis treated with acupuncture. PMID- 7783463 TI - Effects of chai ling tang on proteinuria in rat models. AB - Effects of Chai Ling Tang (a decoction of medicinal herbs) on passive Heymann nephritis (PHN) in rats, a model similar to human membranous nephropathy, were examined. Four hundred mg/kg (body weight) of Chai Ling Tang, or 240 mg/kg B.W. of Xiao Chai Hu Tang, or 130 mg/kg B.W. of Chai Hu (Radix Bupleuri), Ban Xia (Rhizoma Pinelliae) and Sheng Jiang (Rhizoma Zingiberis Recens) were intraperitoneally injected respectively into three groups of female Wistar rats once a day starting from 5 days before intravenous injection of anti-FxlA antibody to the end of the experiment. Another group of rats intraperitoneally injected with phosphate buffered saline (PBS) was used as the control. It was found that the excretion of urinary protein was significantly suppressed in the Chai Ling Tang treated group (52.2 +/- 46.9 mg/day) as compared to that in the PBS control group (276.5 +/- 127.0 mg/day) 15 days after anti-FxlA antibody injection (P < 0.01). The decrease of serum albumin and total protein, and the increase of serum total cholesterol were significantly inhibited in the Chai Ling Tang treated group as compared to that in the control group (P < 0.05, P < 0.05 and P < 0.01 respectively). It is therefore concluded that proteinuria in PHN can be significantly suppressed by Chai Ling Tang. PMID- 7783464 TI - Effect of massotherapy on the in vivo free radical metabolism in patients with prolapse of lumbar intervertebral disc and cervical spondylopathy. AB - The endogenous free radical scavenger superoxide dismutase (SOD) and blood catalase (CAT) in 2 groups of patients with prolapse of lumbar intervertebral disc and cervical spondylopathy were lower than that of the healthy control group, while the -SH reflecting the metabolic disturbance of free radical was higher. After massotherapy, blood SOD and CAT were increased, while lipid peroxide (LPO), -SH in urine were decreased, demonstrating that there are distinct parallel relationships existing in the changes of these enzymes in blood and urine. PMID- 7783465 TI - The effects of massage on the left heart functions in patients of coronary heart disease. PMID- 7783466 TI - Review on acupuncture treatment of peripheral facial paralysis during the past decade. PMID- 7783467 TI - Progress of modern research on tumor blood stasis syndrome and its treatment with the method of promoting blood circulation by removing blood stasis. PMID- 7783468 TI - [Insulin treatment in diabetes mellitus type II: the usefulness of the breakfast test]. AB - BACKGROUND: Insulin treatment in patients with type-II diabetes mellitus (DMII) is normally undertaken by clinical criteria. The aim of the present was to study the efficacy of a standard mixed meal (breakfast test) to predict the need for insulin therapy to thereby evaluate whether it is possible to obtain more objective criteria for the indication of insulin treatment. METHODS: Fifty-six patients with DMII were studied to evaluate the need for insulin therapy over a one-year period. Serum glucose and basal C peptide and their maximum values were determined in all the patients following stimulation with the breakfast test. Insulin treatment was initiated according to exclusively clinical criteria during admission. The patients were followed as out patients for a minimum of 3 months. Treatment at the end of follow up (insulin or no insulin) was evaluated and the results of the test were retrospectively analyzed. RESULTS: The basal C peptide (BCP) values were significantly lower in the individuals requiring insulin in comparison to those who did not require insulin (mean +/- SD 0.64 +/- 0.28 versus 1.18 +/- 0.41 nmol/l, p < 0.0001) similar to what was found with the stimulated maximum C peptide values (MCP) (1.48 +/- 0.77 versus 2.49 +/- 0.63 nmol/l, p < 0.0001). On considering a BCP of less than 0.9 nmol/l for the patients with insulin treatment the sensitivity of BCP was 83.6% and the specificity 78.9%. For a BCP value of less than 1.9 nmol/l sensitivity was 77.7% and specificity 78.9%. Using the values together, sensitivity was 66.6% and specificity 84.4%. CONCLUSIONS: The breakfast test is useful to indicate the need for insulin therapy in patients with type II diabetes mellitus but is not more useful than a determination of isolated basal C peptide. PMID- 7783469 TI - [Changes in the natural history of AIDS in patients from Mallorca and Ibiza: 1986 1992]. AB - BACKGROUND: Longitudinal follow-up studies in patients with human immunodeficiency virus (HIV) infection and AIDS, which are fundamental for the knowledge of variations the natural history of this disease, have generally been carried out by Public Health Departments and in populations in which homosexual males predominate. The aim of the present study was to analyze the changes in the natural history of the patients diagnosed with AIDS in the islands of Mallorca and Ibiza. METHODS: A prospective study of the adult patients diagnosed with AIDS in Mallorca and Ibiza, from 1986 to 1992 was performed. RESULTS: The annual incidence of the cases of AIDS increased throughout the study. The mean age of the patients did not vary, and neither did that in relation to sexes. A progressive decrease was observed in CD4 lymphocytes at the time of diagnosis (from 0.168 x 10(9)/l in 1986 to 0.079 x 10(9)/l in 1992). There was an increase in heterosexual transmission patients with no known risk factors also increased over the period studied. The incidence of extrapulmonary tuberculosis decreased both as the form of presentation and in its global frequency. Pneumonia by Pneumocystis carinii increased mainly as a initial feature. The median survival was 547 days and did not vary significantly throughout the study. CONCLUSIONS: The epidemiologic and clinical study of AIDS in Mallorca and Ibiza, Spain is similar to that observed in other Mediterranean regions. The incidence of extrapulmonary tuberculosis has decreased. PMID- 7783471 TI - [Adolescence: a fertile terrain for drug abuse and addiction]. PMID- 7783470 TI - [The Spanish version of the SF-36 Health Survey (the SF-36 health questionnaire): an instrument for measuring clinical results]. AB - BACKGROUND: The present study, performed within the International Quality of Life Assessment project (including researchers from 15 countries) presents preliminary results of the process of adaptation of the SF-36 to be used in Spain. METHODS: The adaptation was based on the translation/back-translation methodology. Meetings of translators, researchers and patients were organized in order to produce successive versions. A study involving 47 individuals was carried out to assess the relative value (through a visual analogue scale) of each response choice of the questionnaire items. Finally, internal consistency and reproducibility of the Spanish version of the SF-36 was assessed by administering the questionnaire to 46 patients with stable coronary heart disease in two different occasions 2 weeks apart. RESULTS: The average ratings of equivalence of the translated version with the original were high regardless of the difficulty of translation. The rank ordering of mean scores for each responses choice agreed with the ranking assigned in the questionnaire in all cases. Cronbach's Alpha was higher than 0.7 for all dimensions (range: 0.71-0.94) except for Social Functioning scale (alpha = 0.45). Intraclass correlation coefficients between both administrations of the questionnaire ranged from 0.58 to 0.99. CONCLUSIONS: The adaptation process of the SF-36 has concluded with an instrument apparently equivalent to the original and with an acceptable level of reliability. Nevertheless, other basic characteristics of the adapted questionnaire (i.e. validity and sensitivity to changes) should be also assessed. PMID- 7783472 TI - [The genetic markers of arterial hypertension: a long road already begun]. PMID- 7783473 TI - [Adolescents faced with addictive substances: tobacco, alcohol and noninstitutionalized drugs]. AB - BACKGROUND: A large share of premature mortality is Spain in related with the abuse of addictive substances: tobacco, alcohol and non-institutionalized drugs. Adolescence is a key period for the adoption of their use. An accurate knowledge of the attitudes, beliefs, environmental perceptions and behaviours of teen-agers is necessary for the design and evaluation of preventive interventions. METHODS: Data were obtained from a survey conducted in 1992 on smoking, alcohol and non institutionalized drugs in 8th grade students (13-14 years old) of a representative sample of the schools of the city of Barcelona (Catalonia, Spain). RESULTS: Up to 44.1% have ever smoked, 10.9% are regular smokers and 15.5% have bought tobacco at some point. There are no differences in smoking patterns by sex at this age. Even if 35.5% never drink alcohol, 1.7% drink it daily, 15.5% drink on week-ends and 62.9% at family celebrations, while 13.5% have bought alcohol at some point and 22.4% report having got drunk at least once. There are no differences by sex in alcohol use at this age. Concerning non-institutionalized drugs, 35.4% of the students think that many adults use them, and 22.4% say that some friends have tried them. CONCLUSIONS: The results show the increasing penetration of tobacco and alcohol in the personal environment of the students, and the process of initiation. Compared with previous studies in this population, we can estimate a modest and non-significant reduction of regular smoking, and a reduction in daily and regular alcohol use. PMID- 7783474 TI - [Asthenia, anorexia, weight loss, somnolence, abdominal pain and vomiting in a 74 year-old woman]. PMID- 7783475 TI - [Mycoplasma hominis bacteremia in a multiple-trauma patient]. PMID- 7783476 TI - [Emergency admissions to a hospital: the role of primary care]. PMID- 7783477 TI - [Giant-cell aortic arteritis (Takayasu's arteritis) whose presentation simulates infectious aortic endocarditis]. PMID- 7783478 TI - [False melanuria in a female patient treated with 5-ASA for ulcerative colitis]. PMID- 7783479 TI - [Spontaneous bacterial peritonitis due to Salmonella enteritidis]. PMID- 7783480 TI - ["AIDS-ic": belonging or relative to AIDS]. PMID- 7783481 TI - [Monocytoid B-cell lymphoma with peripheral blood expression at the time of its diagnosis]. PMID- 7783482 TI - [Ineffective measures against malpractice by physicians]. PMID- 7783483 TI - [Foot surgery--not all the methods are good]. PMID- 7783484 TI - [Occupational injury and assessment of etiologic factors]. PMID- 7783485 TI - [Patient committees needed also in malpractice cases]. PMID- 7783486 TI - [Dialysis patients are often undernourished]. PMID- 7783487 TI - [Bedside. The portable pencil computer for complete medical history taking in hospitals]. PMID- 7783488 TI - [Cytostatic agents administrated via a subcutaneous intravenous port: the course was a nightmare]. PMID- 7783490 TI - [Nutritional tubes displaced. No dramatic symptoms but the food went down into the bronchi]. PMID- 7783489 TI - [Radical or conservative surgery in craniopharyngioma? Importance of individualized treatment!]. AB - In a retrospective study of 36 children aged 3-16 years, undergoing 'radical' surgery for craniopharyngioma, postoperative radiography showed tumour excision to have been complete in 25 cases and partial in 11 cases. The recurrence rate was 40% among those treated with surgery alone (N = 27), whereas there were no recurrences among those given adjunctive radiotherapy (RT) (N = 9). Although surgery in the hypothalamic region carries a high risk of severe lasting sequelae, long-term follow-up (mean duration 15 years) showed no difference in this respect between the RT and non-RT subgroups. Until large, preferably international, prospective studies may resolve the lack of consensus regarding the optimal treatment of craniopharyngioma, the authors advocate a more individualised approach, the choice between different treatment modalities and combinations being based on tumour size, location and structure. PMID- 7783491 TI - [Arthrosis of the hip and knee. Heredity, sports and overweight are usually more hazardous than work]. PMID- 7783492 TI - [Hand perspiration was his death. The cause was sympathetic imbalance]. PMID- 7783493 TI - [Eye injuries caused by air bags. The importance of information about alkalic aerosol]. PMID- 7783494 TI - [Dialysis treatment is satisfactory. A survey of all patients with chronic renal failure in Stockholm]. PMID- 7783495 TI - [The apparent increase in cancer survival]. PMID- 7783496 TI - [Surgery of colorectal cancer outside the regional hospitals. Good results, but internal specialization is desirable]. PMID- 7783497 TI - [A consensus statement. Heart attack--acute or threatening myocardial infarction]. PMID- 7783499 TI - [Are agreements between private practitioners and county councils welcomed?]. PMID- 7783498 TI - [Children of hiding refugees shall have the right to medical care!]. PMID- 7783500 TI - [Information systems and confidentiality are worth to be discussed]. PMID- 7783501 TI - [A comparative study needed]. PMID- 7783502 TI - [Tuberculosis is coming back. A forgotten knowledge of the infection should be revived]. PMID- 7783503 TI - [Lung x-rays for people seeking asylum! Watch for fever, fatigue, weight loss and prolonged cough to control tuberculosis]. PMID- 7783504 TI - [Hyperthyroxinemia after parathyroidectomy. Not an unusual transient symptomatic condition]. PMID- 7783505 TI - [Sterile water papules against labor pain. A simple, safe, effective method]. PMID- 7783506 TI - [Platelet-derived growth factor. A growth factor of great physiopathological importance]. AB - Platelet-derived growth factor (PDGF) is a 30 kilodalton dimeric peptide comprising A and B chains. The two types of PDGF receptors (alpha and beta) that have been identified belong to the protein-tyrosine kinase family of growth factor receptors. PDGF is a potent mitogen for a variety of cell types, and in gene knock-out experiments has been shown to be required for the development of inter alia mesangial cells of renal glomeruli and smooth muscle cells of lung alveolar septa. PDGF is believed to fulfil important autocrine and paracrine growth-related functions, and its overproduction has been recognised in various malignant tumours and in non-neoplastic hyperproliferative disorders. PMID- 7783507 TI - [Permanent brain damage and fatal outcome. Postoperative hyponatremia--a female Achilles heel?]. PMID- 7783508 TI - [Leonardo da Vinci. A pioneer in the study of blood circulation dynamics]. PMID- 7783509 TI - [Ischemic heart disease: is it really time to change therapeutic routines?]. PMID- 7783510 TI - [Positive stress! Esa-Pekka Salonen about the good stress in the unique leadership role of the conductor... Interview by Birgit Wilhelmson]. PMID- 7783511 TI - [Why do conductors live longer than composers? About working conditions, creation and re-creation]. PMID- 7783513 TI - [Health care at the crossroads--manage or lead? Support responsibility ot the individual persons]. PMID- 7783512 TI - [Life changes after prolonged sick leave]. PMID- 7783514 TI - [Unethical private practice--a privare reaction]. PMID- 7783515 TI - [An unacceptable attempt to silence the critics of the medical society]. PMID- 7783516 TI - [Primary treatment of breast cancer. Axillary dissection is necessary for staging]. PMID- 7783517 TI - [Improve the benefit of axillary excision. At least 10 examined glands should be a standard]. PMID- 7783518 TI - [New therapeutic principles in shoulder instability. Preparatory work is as important as surgery]. PMID- 7783519 TI - [Peripheral nerve tumors. Excirpation may presently be done without disabling neurological loss]. PMID- 7783520 TI - [SVIR, the national intensive care registry. An important evaluation of expensive care]. PMID- 7783521 TI - [Depressive conditions in the elderly and patients with dementia. Underdiagnosed, but curable]. PMID- 7783522 TI - [Working conditions of district medical officers at the turn of the century]. PMID- 7783523 TI - [Recently acquired knowledge of flat adenomas in the large intestine. Hidden precancerous changes demonstrable by endoscopy]. PMID- 7783524 TI - [A case report. Enlarged lymph nodes should give rise to HIV testing]. PMID- 7783525 TI - [From being a student to becoming a good physician. A model project improves the student-teacher relation]. PMID- 7783526 TI - [Chronic non-compliance in connection with prescriptions. Drugs that have been left over - confusing. A prescription instaed of empathy?]. PMID- 7783527 TI - [Olof Joh:Broman--an 18th century dean and self-thought physician: "the clue for good health: everything in moderation is best"]. PMID- 7783528 TI - [Management control in health care. Of what importance is it and towards what is it aimed?]. PMID- 7783529 TI - [Withdraw metformin prior to contrast radiography. A warning in the Fass was forgotten, two patients died]. PMID- 7783530 TI - Shall we nim a horse? PMID- 7783531 TI - Beyond all reasonable DNA. PMID- 7783532 TI - Alcohol and hypertension. PMID- 7783533 TI - To conquer poliomyelitis forever. PMID- 7783534 TI - Diagnosing Prader-Willi syndrome. PMID- 7783535 TI - Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. AB - Lymphoma of gastric-mucosa-associated lymphatic tissue (MALT) type has been linked to infection with Helicobacter pylori. We investigated the effect on MALT lymphoma of eradicating H pylori infection. 33 patients with primary gastric low grade MALT lymphoma associated with H pylori gastritis were treated with omeprazole (120 mg daily) and amoxycillin (2.25 g daily) for 14 days to eradicate H pylori. In addition to histology, PCR was used to examine proliferation of monoclonal B cells before treatment and during follow-up. All patients had at least two post-treatment examinations, and all became negative for H pylori, 2 after a second treatment course. On histology, 23 (70%) patients showed complete regression and 4 (12%) partial regression of lymphoma. 6 (18%) patients had no change after cure of H pylori infection. 1 was treated with chemotherapy. Of 5 treated surgically, 4 were found to have high-grade B-cell lymphoma on histology of the resected stomach and 1 a high-grade T-cell lymphoma. PCR showed complete disappearance of monoclonal B cells after cure of H pylori infection in 13 of 16 patients investigated. During median follow-up of 1 year no relapse of MALT lymphoma occurred. Low-grade primary gastric MALT lymphoma can completely regress after eradication of H pylori infection. However, longer follow-up is needed to clarify whether the remission is lasting. PMID- 7783536 TI - Prevention of relapses in systemic lupus erythematosus. AB - Many relapses of systemic lupus erythematosus (SLE) are preceded by a rise in antibodies against double-stranded DNA (anti-dsDNA). We investigated whether these relapses can be prevented by giving prednisone when a rise in anti-dsDNA occurs. 156 patients with SLE were studied. Anti-dsDNA was measured by Farr assay monthly. When a rise in anti-dsDNA was found, patients were randomly assigned either conventional treatment or 30 mg prednisone added to the current daily dose and tapering off to baseline over 18 weeks. A rise in anti-dsDNA was detected in 46 patients (24 assigned conventional treatment and 22 prednisolone). The relapse rate was higher in the conventional group than in the prednisolone group (20 vs 2, p < 0.001). Although rises in anti-dsDNA in the prednisone group were treated with additional prednisone, the cumulative oral doses of prednisone in the two groups did not differ significantly (p = 0.025). 7 major relapses requiring additional cytotoxic immunosuppressive treatment occurred in the conventional group versus 2 in the prednisone group. Treatment with prednisone as soon as a significant rise in anti-dsDNA occurs prevents relapse in most cases, without increasing the cumulative dose of prednisdone given. PMID- 7783537 TI - Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. AB - Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk. PMID- 7783538 TI - Viridans streptococcal bacteraemia in patients with neutropenia. AB - Viridans streptococcal bacteraemia is frequent in neutropenic patients. 25 neutropenic patients with viridans streptococcal bacteraemia were compared with 64 control patients. Exposure to repeated chemotherapy or cytarabine were independent risk-factors for streptococcal bacteraemia. The use of carboxyureidopenicillins and a stay in laminar-airflow rooms were protective. In a further cohort study of 49 patients, oral streptococci with the same ribotype as blood isolates were recovered from all 7 bacteraemic patients. The oral cavity is a portal of entry for viridans streptococci bacteraemia in neutropenic patients, especially after oral mucosal damage induced by repeated chemotherapy. PMID- 7783539 TI - Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease. AB - Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94.0, interquartile range 256 ng/mL) were significantly higher (p < 0.001) than in 26 control patients (9.5, 15.5 ng/mL). At a cut-off of 35 ng/mL an optimum sensitivity of 80% with a specificity of 92% for the diagnosis of Creutzfeldt Jakob disease by NSE in cerebrospinal fluid was obtained. PMID- 7783540 TI - Preventive health care. PMID- 7783541 TI - Can overall results of clinical trials be applied to all patients? AB - It is generally assumed that the overall results of a clinical trial are generalisable to all patients in the trial and all similar future patients; in other words, that the relative treatment effect in individual patients is similar to the overall trial result. Although this assumption underpins the application of trial results to clinical practice, it has rarely been tested. By independently derived prognostic models, the results of the European Carotid Surgery Trial and the UK-TIA Aspirin Trial were reanalysed to find out whether relative treatment effect varied with absolute baseline risk of stroke. There was significant heterogeneity of relative treatment effect in both trials, resulting in substantial variation in absolute treatment effect with predicted baseline risk. Although, on average, the application of overall trial results to all patients will do more good than harm, a knowledge of the association between relative treatment effect and absolute baseline risk will increase the cost effectiveness of healthcare interventions by identifying those patients in whom treatment is ineffective and those patients who are most likely to benefit. PMID- 7783542 TI - HIV research: a need to focus on the right target. PMID- 7783544 TI - Diabetes update. PMID- 7783543 TI - A continuing community-care crisis. PMID- 7783545 TI - Screening tests: are they worth doing? PMID- 7783546 TI - Neuropsychological effects of exposure to sheep dip. PMID- 7783547 TI - Neuropsychological effects of exposure to sheep dip. PMID- 7783548 TI - Ionomeric cement and aluminium encephalopathy. PMID- 7783549 TI - Time to HIV seroconversion after needlestick injury. PMID- 7783550 TI - Carcinogenic consequences of coal-tar shampoo? PMID- 7783551 TI - Hyperthermia in cancer treatment. PMID- 7783552 TI - Hyperthermia in cancer treatment. PMID- 7783553 TI - Vibrio cholerae O139 in Denmark. PMID- 7783555 TI - Octreotide for protein-losing enteropathy with intestinal lymphangiectasia. PMID- 7783554 TI - Activated-carbon-oriented laparoscopic colectomy. PMID- 7783556 TI - Problems encountered by hearing-impaired people in hospitals. PMID- 7783557 TI - Mortality and social deprivation. PMID- 7783558 TI - Notifying former patients of an infected health-care worker. PMID- 7783559 TI - Pregnancy after intracytoplasmic injection of spermatid. PMID- 7783560 TI - Classification of azoospermic samples. PMID- 7783561 TI - Sudden fall in breast cancer death rates in England and Wales. PMID- 7783562 TI - Colon cancer in a 16-year-old girl. PMID- 7783563 TI - High-dose folic acid treatment for red-cell aplasia. PMID- 7783564 TI - Helicobacter pylori eradication and reinfection. PMID- 7783565 TI - Helicobacter pylori eradication and reinfection. PMID- 7783566 TI - Helicobacter pylori eradication and reinfection. PMID- 7783567 TI - Swabaholics? PMID- 7783569 TI - Patients' health-care decision making: a framework for descriptive and experimental investigations. PMID- 7783568 TI - P-glycoprotein-mediated multidrug resistance in tumor cells: biochemistry, clinical relevance and modulation. PMID- 7783570 TI - The effects of computer-assisted electrocardiographic interpretation on physicians' diagnostic decisions. AB - OBJECTIVE: To evaluate the effect of computer-assisted interpretation of electrocardiograms (ECGs) on diagnostic decision making by primary care physicians. DESIGN: Randomized controlled trial. SETTING: Primary care physicians' outpatient clinics in or near the Minneapolis/St. Paul metropolitan area. PARTICIPANTS: Forty family physicians and general internists who were members of either of two large consortia of clinics. INTERVENTION: Subjects evaluated ten clinical vignettes accompanied by ECGs and reported their diagnostic impressions. The vignettes were based on actual patient visits. Half of the subjects received ECGs with computer-generated reports, the other half received the same ECGs without reports. MAIN OUTCOME MEASURES: ECG reading time; agreement with the clinical diagnosis; agreement with the computer report; diagnostic confidence. RESULTS: The subjects receiving the reports were more likely to agree with the clinical diagnoses of the original cases, particularly for two vignettes in which the diagnoses were uncommon and were mentioned in the reports. The subjects receiving the reports were also more likely to make diagnoses that were consistent with the reports, even when the reports were erroneous. Those receiving the reports spent, on average, 15 seconds less time looking at each ECG, a 25% decrease. CONCLUSIONS: In simulated cases, primary care physicians appear to use computer interpretations of ECGs when available, as shown by enhanced diagnostic accuracy and modestly reduced time spent reading the tracings. However, erroneous reports may mislead physicians. Since the effects of computerized ECG interpretation do not appear to have been uniformly favorable in this mock-clinical setting, it will be important to evaluate the effects of this technology in actual practice. PMID- 7783571 TI - Information seeking in primary care: how physicians choose which clinical questions to pursue and which to leave unanswered. AB - Primary care physicians have many questions about optimal care while they are seeing patients, but they pursue only about 30% of their questions. The authors designed a study to determine the factors that motivate physicians to pursue answers to some of their questions, while leaving the majority of their questions unanswered. They interviewed 49 non-academic primary care physicians during office hours to record clinical questions as they arose in the course of patient care. The physicians then recorded their perceptions of each question with respect to 12 factors expected to motivate information seeking. Two to five days after the interview, each physician was telephoned to determine which questions had been pursued. In a multiple logistic-regression model only two factors were significant predictors of pursuit of new information: the physician's belief that a definitive answer existed, and the urgency of the patient's problem. Other factors, including the difficulty of finding the answer, potential malpractice liability, potential help or harm to the patient, and self-perceived knowledge of the problem, were not significant in the model. Primary care physicians are significantly more likely to pursue answers to their clinical questions when they believe that definitive answers to those questions exist, and when they perceive the patient's problem to be urgent. Medical information systems must be shown to have direct and immediate benefits to solving the problems of patient care if they are to be more widely used by practitioners. PMID- 7783572 TI - The covariance decomposition of the probability score and its use in evaluating prognostic estimates. SUPPORT Investigators. AB - The probability score (PS) or Brier score has been used in a large number of studies in which physician judgment performance was assessed. However, the covariance decomposition of the PS has not previously been used to evaluate medical judgment. The authors introduce the technique and demonstrate it by analyzing prognostic estimates of three groups: physicians, their patients, and the patients' decision-making surrogates. The major components of the covariance decomposition--bias, slope, and scatter--are displayed in covariance graphs for each of the three groups. The decomposition reveals that whereas the physicians have the best overall estimation performance, their bias and their scatter are not always superior to those of the other two groups. This is primarily due to two factors. First, the physicians' prognostic estimates are pessimistic. Second, the patients place the large majority of their estimates in the most optimistic category, thereby achieving low scatter. The authors suggest that the calculational simplicity of this decomposition, its informativeness, and the intuitive nature of its components make it a useful tool with which to analyze medical judgment. PMID- 7783573 TI - Comparison of time-tradeoff utilities and rating scale values of cancer patients and their relatives: evidence for a possible plateau relationship. AB - Because they are easy to administer, rating scales are often used as proxies for utility measures. The authors investigated the relationship between time-tradeoff utilities and rating scale values in two populations: 124 cancer patients asked to evaluate their current states of health and 102 relatives and close friends of cancer patients asked to evaluate health-state scenarios. None of the models tested effectively described the relationship between individual patients' rating scale values and time-tradeoff utilities for their current states of health. In contrast, both a plateau and a power-function model explained the variability in the responses of the relatives reasonably well (R2 = 0.56 and R2 = 0.58, respectively). Given that many respondents who were unwilling to trade off any time assigned rating scale values of well below 100, a plateau model may represent the best approach to adjusting rating scale values for health-state scenarios when it is not feasible to elicit time-tradeoff utilities. PMID- 7783574 TI - Optimal interval for triple-lumen catheter changes: a decision analysis. AB - A survey of 53 university and community hospitals revealed that 73% of the institutions had no standard policy for the replacement of triple-lumen catheters (TLCs). Since the maintenance of a TLC in place for a prolonged period may lead to infectious complications, it appeared warranted that standards of management be developed. A decision-tree model was constructed for evaluating the optimal time for changing a TLC that would minimize infection. Cost estimates and health effects at three-, five-, and ten-day change intervals were considered for catheter insertion and complications resulting from such insertion. The results suggested that prophylactic catheter changes should occur no later than every five days, provided that there are no signs of infection. However, sensitivity analysis of several variables suggested that individual institutions should establish policy timing changes based upon careful interpretation of their own data. A model was developed to assist in determining the optimal time to change a TLC based upon such data. PMID- 7783575 TI - Decision analysis for lower-third-molar surgery. AB - The objective of the study was to identify those factors that should affect treatment planning for patients who have lower third molars, using decision analytic techniques. Utility values based on data from 104 patients indicated that the respondents considered that postoperative complications (except mild pain and temporary paresthesia) reduced health to a greater degree than did complications following non-intervention. A decision analysis indicated that the maximum expected utility of prophylactic third-molar surgery (60.25) was lower than that for non-intervention (76.96). The decision was sensitive to changes in the probabilities of occurrence of recurrent pericoronitis (threshold = 0.52), resorption of an adjacent tooth (threshold = 0.29), loss of an adjacent tooth (threshold = 0.32), and cystic change (threshold = 0.34). These thresholds are much higher than the incidence of problems affecting the lower third molar shown by a concurrent clinical audit and literature review. This study therefore suggests that lower third molars should not be removed prophylactically. PMID- 7783577 TI - Life expectancy biases in clinical decision modeling. AB - Clinical decision models often rely upon survival models predicated on disease specific hazard functions combined with baseline hazard functions obtained from standard life tables. Two biases may arise in such a modeling process. First, life expectancy estimates may be biased even if estimates of survival probabilities are unbiased (misestimation bias). In simulation studies, the authors discovered that the magnitude of misestimation bias is larger as life expectancy increases, sample size decreases, and censoring percentage increases. In the context of a simple decision analysis, they found that imbalances in the sample sizes for the data used to estimate the parameters among different strategies resulted in non-optimal decisions in the long run. The second bias stems from misspecification of the survival model itself (misspecification bias). Using a simple cost-effectiveness model, the authors found that life expectancies and incremental cost-effectiveness ratios differed depending on whether an excess mortality or a proportional-hazards model was specified. In addition, a predictable pattern was observed for these two survival models when extrapolated to other age and gender groups. PMID- 7783576 TI - Communicating the benefits of chronic preventive therapy: does the format of efficacy data determine patients' acceptance of treatment? AB - Patients' informed acceptance of chronic medical therapy hinges on communicating the potential benefits of drugs in quantitative terms. In a hypothetical scenario of treatment initiation, the authors assessed how three different formats of the same data affected the willingness of 100 outpatients to take what were implied to be three different lipid-lowering drugs. Side-effects were declared negligible and costs insured. Subjects make a "yes-no" decision about taking such a medication, and graded the decision on a certainty scale. Advised of a relative risk reduction--"34% reduction in heart attacks"--88% of the patients assented to therapy. All other formats elicited significantly more refusals (p < 0.0001): for absolute risk difference--"1.4% fewer patients had heart attacks"--42% assented; for inverted absolute risk--"treat 71 persons for 5 years to prevent one heart attack"--only 31% accepted treatment. When the data were extrapolated to disease free survival--"average gain of 15 weeks"--40% consented. Similar responses were obtained for descriptions of an antihypertensive drug: 89% assented to therapy when given relative risk reduction but only 46% when given absolute risk reduction. The subjects were confident in both acceptance and refusal: 93% of the decisions were rated "somewhat certain" to "completely certain." The authors conclude that patients' views of medical therapy are shaped by the formats in which potential benefits are presented. Multiple complementary formats may be most appropriate. The results imply that many patients may decline treatment if briefed on the likelihood or extent of benefit. PMID- 7783578 TI - A new model for category-scaling data with an application to the development of health-status measures. AB - Category rating is used to assess patient, family-member, provider, and societal preferences for health outcomes. Often, it is of interest to compare ratings obtained from different groups. Standard methods for making comparisons, such as regressions, correlations, and multiple t-tests, do not account for the dependency among ratings. The authors propose a new model for category ratings that does consider their relative dependency. This model provides a profile of ratings for a single group and facilitates comparisons across groups. It was applied to category ratings for four levels of Bending and Lifting function as defined by the recently developed Functional Capacity Index (FCI). Differences in ratings were observed across groups with different personal experiences of functional limitations and across groups with different degrees of clinical knowledge. These differences were not observed when standard methods were used. Thus, ignoring the relative nature of category ratings can lead to different conclusions about group preferences for health outcomes. When the ratings are being used to scale a health-status measure, this discrepancy has implications for the application of the measure in resource allocation. PMID- 7783579 TI - Explaining distortions in utility elicitation through the rank-dependent model for risky choices. AB - The standard-gamble (SG) method has been accepted as the "gold standard" for the elicitation of utility when risk or uncertainty is involved in decisions, and thus for the measurement of utility in medical decisions. It is based on the assumptions of expected-utility theory. Unfortunately, there is now abundant evidence that expected utility is not empirically valid, and that the SG method overestimates risk aversion and the utilities of impaired health states. This paper shows how rank-dependent utility theory, a newly developed theory in decision science, can explain the main violations of expected utility. Thus it provides a means for correcting the SG method and for improving the assessments of quality-adjusted life years for medical decisions in which there is uncertainty about outcomes. PMID- 7783580 TI - When decision support doesn't support. PMID- 7783581 TI - Improving information search and retrieval for practitioners. PMID- 7783582 TI - [Equipment for computerized radiodiagnosis without film]. AB - The paper deals with the problems which have currently arisen in X-ray diagnosis, such as shortage of film because of its high price, modernization of X-ray equipment, reduction in ray loading. A set of computering filmless X-ray diagnostic tools has been proposed to solve these problems. The implementation of this technology is concerned with the developed MCP-92M system operating in combination with a RUM-20M apparatus. The paper provides the technical characteristics of the system and the principle of operation. Brief data on the use of the system in Novomoskovsk Hospital No. 1 are also given. PMID- 7783583 TI - [Problems of radiation protection in radiodiagnosis]. AB - The paper outlines the ways of technological progress in controlling and recording the dosage loading on the patients undergone X-ray studies. Differences have been established in the concepts "an effective dose" which are proposed by the International Radiation Protection Committee and given in the documents issued by the National State Committee for Standardization. The paper also describes the accepted methods for regulating the patients' dosage loads, which determine the ways of improving X-ray equipment and means of patients' individual protection. PMID- 7783584 TI - [Medical and technical evaluation of drying cabinet for radiologic film ShS-160]. AB - The paper describes the design of a drying cabinet to be equipped in the X-ray laboratories and its testing results. PMID- 7783585 TI - [Educational programs on ventilation-perfusion ratio]. AB - The paper describes a learning programme for calculating the characteristics of arterial blood from the ventilation-perfusion ratios in the lungs by using a three-variable mathematical model of the lung. The lungs are presented as a set of three components which differ in ventilation and perfusion: 1) a fraction of ventilated and O2-perfused alveoles; 2) a fraction of non-perfused and ventilated alveoles; 3) a fraction of unventilated and non-perfused alveoles. Results of calculations are provided. PMID- 7783586 TI - [Non-invasive mapping of cardiac electric potential of a specific quasi epicardium]. AB - A procedure was proposed for non-invasive mapping of the cardiac electrical potential or a spherical quasiepicardium from its synchronous multichannel measurement on the surface of the chest, i.e. routine electrocardiodraphic mapping. Mathematical simulation was used to demonstrate that the quasiepicardial potential can be calculated with the accuracy sufficient for clinical diagnosis by applying the multipole electric field resolution method with allowance made for three lowest resolution terms. Due to the fact that the spherical quasiepicardium is more approximate to the heart and more concentric as to its center than the chest surface, the maps of the quasiepicardial potential permit recognition of some features of the pattern of a cardiac electric process, which do not manifest themselves in the distribution of the potential on the body's surface. The examples showing that the assessment of a cardiac abnormality can be made more accurate by using this method are given in the paper. PMID- 7783587 TI - [Basic characteristics of magnetic resonance tomographs "Obraz"]. AB - This paper described block diagrams of national magnetic tomographs having a 0.12 T resistive magnet and gives their comparative characteristics , indicated the optimal modes of their operation. PMID- 7783588 TI - [Computerized devices for biological testing]. AB - The paper provides evidence for perspectives of the toxicological equipment for protozoa chemotaxis bioassay, which allows one to solve the problems in preparing a culture, a sample, testing solutions and measurement of protozoan reactions. A Poisson process device was proposed to use for construction of a mathematical model of a protozoan concentration transducer. The experimental findings supported the dependence theoretically forwarded. With the new approach, a BIOTESTER-2 device was designed, which has found its use in controlling the quality of water, antibiotics, in mapping the contamination of areas. The device may be used in the evaluation of the toxicity of biological fluids. PMID- 7783589 TI - [Automated processing of electrophysiologic signals]. AB - The paper outlines a diagram of a multichannel analyzer of electrophysiological signals while are significantly non-stationary (such as those of electroencephalograms, myograms, etc.), by using a method based on the ranging procedure by the change-over points which may be the points of infection, impaired locality, minima, maxima, discontinuity, etc. PMID- 7783590 TI - [Methodologic aspects of combined physiotherapeutic effect]. AB - The paper describes a conceptually logic and mathematical model of the body's responses to the combined exposure to several physiotherapeutical factors. The model has been developed by transforming the basic differential equation of Volterra's survival theory and realizing as a computer program. The model enables one to find the optimal combinations of the parameters of the influencing factors which produce the maximum therapeutical effect without exhausting the compensatory abilities of the body's physiological systems. PMID- 7783591 TI - [Design and serial manufacturing of medical equipment in the Siberia and the Far East]. PMID- 7783592 TI - [Guidelines of European Federation of Societies of Medical Physics (EFSMP)]. PMID- 7783593 TI - [Automatization of the workplace of radiologist]. AB - The authors propose and implement a roentgenologist's IBM PC/AT-compatible computer-aided automatic working place designed for the digital processing and analysis of medical introscopic images. The two-levelled architecture of APM-BP software allows one to optimize the speed of computations and to apply as computer technologies the know-how and experience gained in solving specific problems in the analysis of informative features of medical images. A procedure for the digital processing of linear pulmonary tomograms by using the designed working place in order to solve the problems of preclinical diagnosis of peripheral lung cancer is described. PMID- 7783594 TI - Identification of differentially expressed genes in scrapie-infected mouse neuroblastoma cells. AB - In vitro cDNA libraries from scrapie-infected and non-infected murine neuroblastoma cell lines were screened with cDNA probes derived by subtractive hybridization from scrapie-infected and uninfected cells to identify genes with altered expression associated with scrapie infection. Eleven independent recombinant clones, whose expression was either increased or decreased in scrapie infected cells, were identified. Expression of these genes was also analyzed in a panel of scrapie-infected and non-infected cell lines. Five genes had altered mRNA expression in most scrapie-infected neuroblastoma cell clones compared to non-infected clones. These genes were chromogranin B, intracisternal-A particle envelope, ornithine decarboxylase antizyme, heat shock protein 70 and one unidentified gene. None of these alterations in gene expression was uniquely scrapie-specific; however, the skewed association of increased expression with scrapie infection suggested that a causal relationship might exist between scrapie infection and altered expression of these genes in mouse neuroblastoma cells in vitro. PMID- 7783595 TI - Protection of SJL/J mice from demyelinating disease mediated by Theiler's murine encephalomyelitis virus. AB - Intracerebral infection with the DA strain of Theiler's murine encephalomyelitis virus induces a chronic demyelinating disease in SJL/J mice. Intraperitoneal inoculation with either the wild-type DA virus or an attenuated variant virus of DA, H7A6-2, results in protection from development of chronic demyelinating disease. Protective anti-viral immune responses result in reduced viral titers and decreased inflammation in the central nervous system within the first week following intracerebral challenge with virus. Development of protective immunity requires the presence of B cells and CD4+ T cells but does not require CD8+ T cells. High titers of serum anti-viral IgG and neutralizing antibodies are induced following the intraperitoneal inoculation with the DA virus or H7A6-2 virus prior to challenge. While protection could not be transferred with immune serum from DA virus-infected mice or neutralizing monoclonal antibodies, protection was correlated with increased numbers of DA virus-specific plasma cells in the central nervous system within the first week following intracerebral challenge. Protected mice also had enhanced levels of anti-DA virus IgG and neutralizing antibodies in the cerebral spinal fluid by 1 week following intracerebral challenge with DA virus. Thus, we conclude that vaccination with live virus results in protection from chronic demyelinating disease by inducing immune responses which are manifested in the central nervous system and rapidly clear infection after intracerebral challenge with DA virus. PMID- 7783597 TI - Serum bactericidal activity and phagocytosis in host defence against Haemophilus ducreyi. AB - Serum bactericidal activity and phagocytic killing are two important mechanisms involved in the host defence against bacteria. Using some in vitro methods, serum bactericidal assay, phagocytic killing by polymorphonuclear leukocytes (PMN) and chemiluminescence, we have evaluated the significance of these mechanisms in the killing of Haemophilus ducreyi bacteria. Furthermore, induction of C3 conversion and deposition of immunoglobulins, C1q and C3, on the surface of bacteria was studied by crossed immunoelectrophoresis and ELISA, respectively. Transmission electron microscopy was employed to study internalization of bacteria by PMN. H. ducreyi and lipooligosaccharide preparations from these bacteria were able to induce conversion of complement factor C3 in normal human serum (NHS). Exposure of bacteria to NHS resulted in deposition of IgG, IgM and complement factors C1q and C3 on the surface of bacteria. H. ducreyi bacteria lost their viability when incubated with fresh but not inactivated normal serum at high concentrations, indicating that the bacteria are sensitive to the complement-dependent bactericidal activity of serum. There were some variations between different strains regarding their susceptibility to the bactericidal activity of NHS, but for eight strains tested, all of the bacteria exposed were not killed in medium containing up to 70% of fresh serum. Complement-mediated opsonophagocytic killing of H. ducreyi by PMN was more effective than complement-dependent bactericidal activity of fresh normal sera. Bacteria treated with heat inactivated immune sera, on the other hand, were as sensitive to the bactericidal effect of PMN as those treated with non-inactivated immune sera, indicating the role of antibodies in opsonophagocytosis. H. ducreyi bacteria were also killed by PMN in the absence of serum antibodies and complement. Using the chemiluminescence assay, H. ducreyi was shown to activate PMN in the absence of serum as well as after opsonization with complement and antibodies. Our results therefore indicate that both opsonic- and non-opsonic mechanisms are involved in the phagocytosis and the subsequent killing of H. ducreyi bacteria. Although both complement and antibodies enhance the ability of phagocytes to kill H. ducreyi, neither component is sufficient for effective killing of H. ducreyi. PMID- 7783596 TI - Molecular cloning of an Actinobacillus pleuropneumoniae outer membrane lipoprotein (OmlA) from serotype 5a. AB - The gene encoding an outer membrane lipoprotein (OmIA) was cloned from Actinobacillus pleuropneumoniae strain NG-8 (serotype 5a). The deduced amino acid sequence of OmIA from strain NG-8 showed 61% identity to the OmIA from serotype 1 strain, which confers protective immunity to pigs. Southern blot analysis showed the presence of a sequence highly homologous to the omIA gene of strain NG-8 in strains of serotype 5a, 5b and 10. A specific serum against OmIA of NG-8 also detected a homologous protein in the strains of these serotypes. These data shows the presence of antigenic variability among A. pleuropneumoniae OmIA proteins. PMID- 7783598 TI - Streptokinase activity among group A streptococci in relation to streptokinase genotype, plasminogen binding, and disease manifestations. AB - Certain genotypic variants of streptokinase (ska) of beta-hemolytic streptococci group A have been associated with acute post-streptococcal glomerulonephritis (APSGN). In our earlier studies on strains isolated from Ethiopian children with various streptococcal disease manifestation, we reported an even distribution of streptokinase genotypes with no association to disease patterns. Considering the possibility that strains could differ in their ability to secrete the protein, levels of streptokinase activity in culture supernatants of these strains were determined by a plasminogen activation assay using a synthetic tripeptide, H-D valyl-leucyl-lysin-p-nitroaniline, as a substrate. Of the 53 streptococcal group A strains, ten (19%), which belonged to genotype ska4 and ska8, did not activate human plasminogen. These strains did not activate bovine, sheep, horse, rabbit or porcine plasminogens either. They represented at least five M protein and non typeable serotypes, and were characterized by high human plasminogen binding activity. Six of the 53 strains (11%) harbouring genotype ska3 and ska7 showed low levels of human plasminogen activation. Strains of ska1 and ska2, 37/53, activated human plasminogen at a higher level (p < 0.005). Levels of plasminogen activation were not significantly different among the ska1 and ska2 strains associated with various streptococcal disease manifestations. Antibody levels against streptokinase were higher (p < 0.05) in convalescent sera from acute rheumatic fever and APSGN patients in comparison with sera from other patient categories and healthy controls. Streptokinase genotype and in vitro streptokinase production do not correlate directly to streptococcal disease manifestation, indicating a probable significance of additional streptococcal and/or host factors in the initiation of APSGN. PMID- 7783599 TI - Confirmation that DNA encoding the major fimbrial subunit of Av24 fimbriae is homologous to DNA encoding the major fimbrial subunit of F107 fimbriae. AB - Plasmid DNA from porcine enterotoxigenic Escherichia coli strain Av24 (O141:K85ab) was cloned into recipient E. coli strain JM105 using the plasmid vector pUC18. Clones were obtained that produced fimbriae which reacted with antisera specific to the fimbriae produced by strain Av24. Restriction mapping of cloned DNA, PCR with fedA primers and DNA sequencing showed a portion of the cloned DNA to be homologous to that encoding the major fimbrial subunit of F107 fimbriae. This confirms that the fimbriae possessed by strains of E. coli causing both edema disease and post-weaning diarrhoea in piglets are variants of the same fimbriae. PMID- 7783600 TI - Improved techniques for kidney transplantation in mice. AB - Improved microsurgical techniques for kidney transplantation in the mouse are described. Left renal transplantation is performed with end-to-side anastomoses of the donor renal vein to the inferior vena cava and the donor aortic cuff to the aorta. Urinary tract reconstruction is accomplished by suturing the donor ureter with a bladder patch to the recipient bladder. With these modifications, it is possible to achieve success rates as high as 90%. This stable and reproducible model provides a useful tool to study the immunological mechanisms of kidney allograft rejection at the molecular level. PMID- 7783601 TI - Development of a mouse aortic transplant model of chronic rejection. AB - Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat aortic allograft, has histologic features that parallel those in the vessels of human transplanted organs. However, the molecular tools required to dissect the immunology of chronic rejection are unavailable in the rat. We developed aortic transplantation in the mouse as a new model of chronic rejection. This will allow the use of the diversity of recombinant cytokines and monoclonal antibodies available for the mouse and its well-defined genetics to investigate chronic rejection in greater detail. We describe the perioperative care and surgical technique for the model in which a 1 cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal arteries and above the aortic bifurcation. Mortality rates were initially high (70%) due to thrombosis and shock. Changes in technique and operator facility resulted in a high rate of success (75%). After 192 operations, the current success rate is > 80%. Mice free from complications at 12 hrs postop had indefinite survival, and after 2 months the typical vascular lesion of chronic rejection was present. This new model of chronic rejection will be a valuable tool to study the molecular immunology and genetics of chronic rejection. PMID- 7783602 TI - Hemodynamic study of different angled end-to-side anastomoses. AB - This study assessed the postoperative microvascular hemodynamics in end-to-side arterial anastomoses of varied angles in order to determine whether the angle of the anastomosis affects arterial flow. Thirty male rats were divided into three groups of ten. Carotid to carotid end-to-side anastomoses were performed with anastomotic angles of 45, 90, and 135 degrees. Postoperative flow was assessed using high frequency pulsed Doppler ultrasound (HFPDU) at 30 and 120 min postoperatively. Measurements at 30 min demonstrated significant differences in flow, with the 45 degrees grafted vessels utilizing 56.5% of total carotid flow, and the 90 degrees and 135 degrees anastomoses appropriating 46.5% and 43.2% of flow, respectively (comparing 45 degrees to both 90 degrees, P < 0.05, and 135 degrees, P < 0.002). The change from baseline in 45 degrees and 90 degrees groups dissipated over a 2 hr postoperative period, but flow in the grafted vessels in the 135 degrees group continued well below 50% at 39.9% (comparing to both 45 degrees and 90 degrees, P < 0.001), thereby displaying a significant difference in the postoperative arterial flow of varied angled microanastomoses. PMID- 7783603 TI - New burst test method for comparing strengths of blood vessel repairs. AB - An in vivo system was developed which allows researchers to determine the intraluminal pressures necessary to burst anastomosed blood vessels. Rat femoral arteries underwent standard microsurgical anastomoses and sham surgeries. After 6 min of leak-free blood flow, the vessels were ligated and cannulated with PE 50 tubing. The catheter was tied into position with 6-0 suture, constructing a water tight balloon of tissue inclusive of the repair site around the tubing, then attached via a "Y" adapter to a pressure transducer with a digital readout and to a saline filled syringe in an infusion pump. The digital readout from the transducer accurately expressed the pressure on the anastomosis. The highest pressure recorded when the anastomosis ruptured was taken to be the anastomotic burst pressure. Mean burst pressure for 9 suture anastomoses was 326 mm mercury. All vessel burst pressures exceeded rat mean systolic pressure; 90% exceeded rat maximum systolic pressure. All sham surgeries failed to burst, even at pressures exceeding 1,500 mm Hg. The burst pressure test clearly provides researchers with a valid quantitative measure for in vivo comparison of the efficacies of various anastomotic techniques. PMID- 7783604 TI - Rat tail: a useful model for microvascular training. AB - The rat femoral vessel model is widely used as the basic model for microvascular training; however, it offers only a limited number of anastomoses and vessel sizes. Rat tail vessels provide long length, almost as long as the tail; adequate diameters, from about 1 mm to 0.2 mm; as well as the economy and a convenient location for practicing microvascular anastomoses. It is also the best choice for anastomosing vessels smaller than 0.5 mm diameter. Using stored, frozen tails harvested from sacrificed rats of other projects makes it even more frugal and convenient. Hence, it is an ideal model for microvascular training. The related anatomy and dissecting method are described and discussed. PMID- 7783605 TI - The first elective free flap in a cardiac transplant patient. AB - A case of free fibula transfer for mandibular reconstruction in a cardiac transplant patient is described. The reconstructive microsurgeon should be aware of the special requirements of these immunosuppressed patients and flap transfer should be performed in specialized centers with the interaction of different specialties to make the procedure safe and successful. PMID- 7783606 TI - Vascularized fibular graft for bone reconstruction of the extremities after tumor resection in limb-saving procedures. AB - We treated 18 patients (8 males and 10 females) with bone or soft tissue tumors in the extremities by vascularized fibular grafts (VFGs). The average age was 29 years. Two had malignant soft tissue tumors in the forearm (angiosarcoma and synovial sarcoma) and the other 16 had bone tumors [osteosarcoma (8), chondrosarcoma (3), angiosarcoma (1), adamantinoma (1), and giant cell tumor (3)]. Affected sites of the bone tumor cases were tibia (5), femur (5), humerus (3), radius (2), and ulna (1). According to the surgical staging system of Enneking et al. 1 patient was in stage III, 12 in IIB, 2 in IB, and 3 in IA. The surgical margin was curative in 5 patients, wide in 9, marginal in 2, and intralesional in 2. One patient died due to lung metastasis although bone union was obtained by the VFGs. Functional results of the bone reconstruction in the remaining 17 patients were evaluated according to the modified scale of Enneking et al. The VFGs resulted in substantial bone unions in all patients except 1. Bone unions in all 17 patients occurred in less than 10 months. Overall clinical results were satisfactory. Based on a 30-point scale overall clinical results ranged from 10 to 30 points with an average of 21 points. Functional evaluation in the upper extremity were, generally, superior to those in the lower extremity. Postoperative complications were 5 metastases (4 in the lung and 1 in the mediastinum) in 4 patients, 1 recurrence, and 2 fractures after obtaining bone union. One patient died from metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783607 TI - Inside-out vein graft repair compared with nerve grafting for nerve regeneration in rats. AB - The inside-out vein graft is a vein conduit pulled through itself to invert the normal orientation and place the adventitial layer within the lumen of the conduit. Our study compares regeneration of peripheral nerves in the rat through two conduits: inside-out graft of the jugular vein and autogenous nerve graft. In 10 rats, the right jugular vein was harvested, turned inside out, and used to bridge a 10 mm defect created in the right sciatic nerve. The 10 mm nerve segment from the right was then used as a standard nerve graft to bridge a 10 mm gap created in the left sciatic nerve. Rats were sacrificed at 8 and 12 weeks. Regeneration on the inside-out vein graft side showed superior functional results (faster conduction velocities) and improved histological results (greater axon counts) compared with the nerve grafted side. We feel the adventitial surface of the wall of the vein promotes nerve regeneration by providing an environment rich with collagen, laminin, and Schwann cells and promotes increased vascularization of the new nerve. PMID- 7783608 TI - Experimental model for local administration of nerve growth factor in microsurgical nerve reconnections. AB - An experimental model for local administration of neuronotrophic substances at the site of peripheral nerve lesion is presented. The model consists of a subcutaneously located silicone reservoir and a connecting tube with its distal end fixed in the proximity of the severed and repaired nerve. The results of the preliminary tests of the model are presented. Sixty Sprague-Dawley rats were divided into two groups: control (saline-treated) (n = 30) and NGF-treated (n = 30). After axotomy of the sciatic nerve, an epineurial repair is performed. NGF or saline is injected daily into the subcutaneous reservoir during the first 3 weeks after axotomy and a single dose in the fourth week. The regenerated nerve observed in the NGF-treated group after four weeks of treatment presents a greater percentage of myelinated axons, thicker myeline sheaths, and more mature endoneurial layers. This experimental model provides a reliable and quantitative way to deliver neuronotrophic substances in site and at different administration rates. PMID- 7783609 TI - The rat brachial plexus and its terminal branches: an experimental model for the study of peripheral nerve regeneration. AB - Despite the introduction of microsurgical techniques into clinical practice, the results of surgical procedures involving the brachial plexus and peripheral nerves are still far from spectacular. We therefore studied the rat brachial plexus and its terminal branches in 203 rats. Detailed anatomic and morphologic analyses of the biceps brachii and musculocutaneous nerve, finger flexors, flexor carpi radialis, and the median nerve were performed. Various sources of conventional and vascularized nerve grafts were explored. After musculocutaneous nerve section or median nerve section, there were no articular contractures or automutilations, which constitutes an advantage for these experimental models over the sciatic nerve model. The brachial plexus and its terminal branches provide a good experimental model which can be used to assess the development and normal control of muscle function, examine the mechanisms underlying functional recovery, and test the effects of treatments to enhance recovery. PMID- 7783610 TI - Improved reflow and viability in reperfused ischemic rat island groin flaps using dexamethasone. AB - Reperfusion injury and the no-reflow phenomenon are manifestations of a complex series of events that culminate in an acute inflammatory reaction within reperfused tissue. Antiinflammatory therapy attenuates ischemia-reperfusion injury. The purpose of this study is to evaluate the effects of dexamethasone on blood flow and viability of ischemic rat island groin flaps. Thirty-three mature male Sprague-Dawley rats were divided into 3 groups. The flaps were subjected to 8 hr of ischemia in the control and treatment groups. Fluorescein studies were performed, and flap viability was assessed. Twenty-four hour fluorescence (after reperfusion) correlated very closely with the percentage of eventual flap viability. The blood flow and viability of the treatment group flaps were significantly better than those in the ischemic control group. Dexamethasone significantly improved ischemic flap survival in the rat 8 hr ischemic island groin flap model in our study. PMID- 7783611 TI - Intravascular heparin protects muscle flaps from ischemia/reperfusion injury. AB - Heparin has been found to decrease ischemia/reperfusion injury in skeletal muscle and other tissue/organ systems. The timing of heparin administration to the muscle vasculature has not been explored. We investigated the use of heparinized blood as a washout solution during ischemia to reduce ischemia/reperfusion injury. A rat cutaneous maximus muscle free flap was subjected to a 10-hr period of room temperature ischemia, then was heterotopically transplanted to the groin via microsurgical revascularization to the femoral vessels. In three experimental groups, flaps were subjected to brief ex vivo perfusion with autologous heparinized blood, at 2, 5, or 8 hr into the 10-hr ischemic interval. In the two other groups, the flaps were not perfused, and the animals were systemically heparinized either before ischemia or before transplantation, respectively. A control group underwent no flap perfusion or systemic heparinization. After transplantation, flaps were given a 48-hr period of in vivo reperfusion, then were harvested for evaluation. Flaps undergoing ex vivo perfusion or preischemic heparinization had no significant differences in weight gain (edema) compared with flaps receiving posttransplant heparinization or no heparinization (controls). The dehydrogenase staining of muscle biopsies was significantly faster (indicative of viable tissue) for perfused flaps and the flaps for which the animals received preischemic heparinization, when compared with flaps for which the animals received posttransplant heparinization or no heparinization. From these results, we conclude that heparin offers protection from ischemia/reperfusion injury when it can be introduced into the vascular network either prior to or during the ischemia period. These findings suggest the possibility of using heparinized washout solutions to enhance survival in amputated extremities. PMID- 7783612 TI - Experimental microvenous thrombosis following anastomosis with a knotted suture. AB - An experimental model for producing venous thrombosis was developed in end-to-end anastomoses of femoral veins in rats. The anastomoses were performed using a suture (9-0 suture-70 microns needle) with a knot 1 cm from the needle. The knot was formed by making either six or eight half-hitches in one throw of the suture. Vessel patency was assessed through the direct "milking test" at 20 min and 24 hrs. The incidence of thrombosis when using one knot with six half-hitches ranged from 20% to 40% and with eight half-hitches, from 50% to 70%. The incidence of femoral vein thrombosis varied directly with the presence and size of the knot. In this model, thrombosis was induced by exaggerating vessel injuries that may occur when performing routine microvascular anastomoses. This study demonstrates a reproducible thrombogenic model which mimics clinical practice and may be used to study the effects of local and systemic antithrombogenic agents. PMID- 7783613 TI - Alkaliphiles: 'basic' molecular problems of pH tolerance and bioenergetics. AB - Alkaliphilic Bacillus species provide experimental opportunities for examination of physiological processes under conditions in which the stress of the extreme environment brings issues of general biological importance into special focus. The alkaliphile, like many other cells, uses Na+/H+ antiporters in pH regulation, but its array of these porters, and other ion-flux pathways that energize and support their activity, result in an extraordinary capacity for pH homeostasis; this process nonetheless becomes the factor that limits growth at the upper edge of the pH range. Above pH 9.5, aerobic alkaliphiles maintain a cytoplasmic pH that is two or more units below the external pH. This chemiosmotically adverse delta pH is bypassed by use of an electrochemical gradient of Na+ rather than of protons to energize solute uptake and motility. By contrast, ATP synthesis occurs via completely proton-coupled oxidative phosphorylation that proceeds just as well, or better, at pH 10 and above as it does in the same bacteria growing at lower pH, without the adverse pH gradient. Various mechanisms that might explain this conundrum are described, and the current state of the evidence supporting them is summarized. PMID- 7783614 TI - Identification of a novel cellulose-binding domain within the multidomain 120 kDa xylanase XynA of the hyperthermophilic bacterium Thermotoga maritima. AB - A segment of Thermotoga maritima strain MSB8 chromosomal DNA was isolated which encodes an endo-1,4-beta-D-xylanase, and the nucleotide sequence of the xylanase gene, designated xynA, was determined. With a half-life of about 40 min at 90 degrees C at the optimal pH of 6.2, purified recombinant XynA is one of the most thermostable xylanases known. XynA is a 1059-amino-acid (approximately 120 kDa) modular enzyme composed of an N-terminal signal peptide and five domains, in the order A1-A2-B-C1-C2. By comparison with other xylanases of family 10 of glycosyl hydrolases, the central approximately 340-amino-acid part (domain B) of XynA represents the catalytic domain. The N-terminal approximately 150-amino-acid repeated domains (A1-A2) have no significant similarity to the C-terminal approximately 170-amino-acid repeated domains (C1-C2). Cellulose-binding studies with truncated XynA derivatives and hybrid proteins indicated that the C-terminal repeated domains mediate the binding of XynA to microcrystalline cellulose and that C2 alone can also promote cellulose binding. C1 and C2 did not share amino acid sequence similarity with any other known cellulose-binding domain (CBD) and thus are CBDs of a novel type. Structurally related protein segments which are probably also CBDs were found in other multidomain xylanolytic enzymes. Deletion of the N-terminal repeated domains or of all the non-catalytic domains resulted in substantially reduced thermostability while a truncated xylanase derivative lacking the C-terminal tandem repeat was as thermostable as the full-length enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783615 TI - Induction of phospholipase- and flagellar synthesis in Serratia liquefaciens is controlled by expression of the flagellar master operon flhD. AB - When a liquid culture of Serratia spp. reaches the last part of the logarithmic phase of growth it induces the synthesis of several extracellular hydrolytic enzymes. In this communication we show that synthesis and secretion of the extracellular phospholipase is coupled to expression of flagella. Expression of flagella is demonstrated to follow a growth-phase-dependent pattern. Cloning, complementation studies and DNA-sequencing analysis has identified a genetic region in Serratia liquefaciens which exhibits extensive homology to the Escherichia coli flhD flagellar master operon. Interruption of the chromosomal flhD operon in S. liquefaciens results in non-flagellated and phospholipase negative cells, but the synthesis of other exoenzymes is not affected. By placing the flhD operon under the control of a foreign inducible promoter we have shown that increased transcription through the flhD operon leads to induction of flagellar synthesis and phospholipase expression. PMID- 7783616 TI - comK encodes the competence transcription factor, the key regulatory protein for competence development in Bacillus subtilis. AB - comK is a positive autoregulatory gene occupying a central position in the competence-signal-transduction network. All regulatory routes identified in this network converge at the level of comK expression. The ComK protein is required for the transcriptional induction of comK and the late competence genes, which specify morphogenetic and structural proteins necessary for construction of the DNA-binding and uptake apparatus. In this report we demonstrate that ComK specifically binds to DNA fragments containing promoter and upstream sequences of the genes it affects (comC, comE, comF, comG and comK). Using portions of the region upstream of comC we show that the ComK-binding sequences are essential for the expression of competence. Moreover, we demonstrate that the presence of ComK stimulates the expression of comF-lacZ and comG-lacZ translational fusions in vivo in Escherichia coli. These results indicate that the gene product of comK is identical to the previously inferred competence transcription factor (CTF). PMID- 7783617 TI - Plasmodium falciparum protein associated with the invasion junction contains a conserved oxidoreductase domain. AB - The merozoite cap protein-1 (MCP-1) of Plasmodium falciparum follows the distribution of the moving junction during invasion of erythrocytes. We have cloned the gene encoding this protein from a cDNA library using a monoclonal antibody. The protein lacks a signal sequence and has no predicted transmembrane domains; none of the antisera reacts with the surfaces of intact merozoites, indicating that the cap distribution is submembranous. MCP-1 is divided into three domains. The N-terminal domain includes a 52-amino-acid region that is highly conserved in a large family of bacterial and eukaryotic proteins. Based on the known functions of two proteins of this family and the pattern of amino acid conservation, it is predicted that this domain may possess oxido-reductase activity, since the active cysteine residue of this domain is invariant in all proteins of the family. The other two domains of MCP-1 are not found in any other members of this protein family and may reflect the specific function of MCP-1 in invasion. The middle domain is negatively charged and enriched in glutamate; the C-terminal domain is positively charged and enriched in lysine. By virtue of its positive charge, the C-terminal domain resembles domains in some cytoskeleton associated proteins and may mediate the interaction of MCP-1 with cytoskeleton in Plasmodium. PMID- 7783618 TI - Regulation of succinate dehydrogenase (sdhCDAB) operon expression in Escherichia coli in response to carbon supply and anaerobiosis: role of ArcA and Fnr. AB - Succinate dehydrogenase (SDH) of Escherichia coli, the sole membrane-bound enzyme of the tricarboxylic acid cycle, participates in the aerobic electron-transport pathway to generate energy via oxidative phosphorylation reactions. Previous studies have established that succinate dehydrogenase (SDH) synthesis is elevated by aerobiosis and suppressed during growth with glucose. To examine how the sdhCDAB genes that encode SDH are regulated by changes in the environment, sdh lacZ fusions were constructed and analysed in vivo following cell growth under a variety of alternative culture conditions. Expression of sdh-lacZ was highest under aerobic conditions and was decreased 10-fold in the absence of oxygen. The fnr and arcA gene products are required for this oxygen control and each acts to repress sdhC-lacZ expression. Expression of sdh-lacZ also varied 10- to 14-fold depending on the type of carbon substrate used or the medium richness. This control was shown to be independent of the crp and fruR gene products, and indicates that some other regulatory element exists in the cell to adjust SDH enzyme levels accordingly. Iron and haem availability affected sdhC-lacZ expression by two- to three-fold. Lastly, sdhC-lacZ expression was shown to vary with the cell growth rate during aerobic and anaerobic conditions. PMID- 7783619 TI - Genetic suppression and phenotypic masking of a Myxococcus xanthus frzF- defect. AB - An insertion of transposon Tn5-lac, omega 4519, generates a lacZ fusion with a Myxococcus xanthus promoter expressed during both vegetative growth and development. Sequence analysis of the junction of omega 4519 with M. xanthus DNA shows that the insertion is in frzF, a homologue of cheR from Salmonella typhimurium. When frzF- (or frzCD-) cells are starved for nutrients at modest densities, they aggregate to form a radial pattern and produce fewer than 1% of the wild-type complement of spores. At higher densities, frzF::omega 4519 cells form 'frizzy' aggregates and produce 80-90% of the wild-type complement of spores. In contrast, when cells with both a frzF- (or frzCD-) and an sglA1 mutation are allowed to develop at either low or high cell densities, they produce frizzy aggregates containing a near wild-type complement of heat resistant spores. In addition to suppressing the density dependence of fruiting body morphogenesis, the sglA1 mutation also suppresses the sporulation defect caused by two different frzF- mutations and a frzCD- mutation. In contrast, a mutation in a different S motility gene, sglG1, does not suppress the frz- mutations. Thus, the suppression of frz- mutations by sgl- mutations is allele specific, and depends on the sgl allele, but not the frz allele. Because the phenotypes of frz- mutations have been determined in a (suppressing) sglA1 genetic background, the frz genes may play more central roles in development than initially recognized. PMID- 7783620 TI - Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae. AB - Cloning and sequencing of the IgA1 protease gene (iga) from Neisseria meningitidis strain HF13 showed an overall structure equivalent to iga genes from Neisseria gonorrhoeae and Haemophilus influenzae, although no region corresponding to the gonococcal alpha-peptide was evident. An additional 18 N. meningitidis and 3 H. influenzae iga genes were amplified by the polymerase chain reaction technique and sequenced corresponding approximately to the N-terminal half of the mature enzyme. Comparative analyses of a total of 29 iga genes showed that pathogenic Neisseria have iga genes with a significantly lower degree of heterogeneity than H. influenzae iga genes. Recombinational events indicated by mosaic-like structures corresponding to those found among N. gonorrhoeae protease genes were detected among N. meningitidis iga genes. One region showed characteristic differences in sequence and length which correlated with each of the different cleavage specificities. Meningococci were extremely conserved in this region with no evidence of recombination between isolates of different cleavage specificities. Sequences further downstream showed no obvious relationship with enzyme cleavage type. This region consisted of conserved areas interspersed with highly variable areas. Amino acid sequence homologies in the variable regions of meningococci reflected the antigenic types defined by using polyclonal neutralizing antibodies. PMID- 7783621 TI - Overexpression of the Shigella flexneri genes coding for DNA topoisomerase IV compensates for loss of DNA topoisomerase I: effect on virulence gene expression. AB - Introducing the Escherichia coli topA20::Tn10 allele to Shigella flexneri results in osmotic sensitivity, a reduced growth rate, an increase in reporter plasmid supercoiling (all common to the E. coli mutants), an inability to grow on MacConkey agar and a loss of virulence gene expression. E. coli mutants harbouring this topA allele often compensate for the loss of DNA topoisomerase I by amplifying the genes coding for topoisomerase IV. Unlike the E. coli topA mutants, derivatives of S. flexneri harbouring this topA allele did not appear to acquire any compensatory mutations. We investigated the possibility that this was due in part to an inability of the S. flexneri topoisomerase IV genes to compensate for loss of DNA topoisomerase I when overexpressed. The S. flexneri genes encoding the alpha- and beta subunits of topoisomerase IV were detected and cloned in separate multicopy plasmids. These plasmids complemented well characterized Salmonella typhimurium temperature-sensitive topoisomerase IV mutations, showing that the S. flexneri and S. typhimurium proteins are capable of combining to form active complexes. When the S. flexneri topoisomerase IV genes were cloned in the same multicopy plasmid and introduced into a S. flexneri topA mutant, the plasmid restored osmotic tolerance, improved the growth rate, allowed growth on MacConkey indicator plates and resulted in a relaxation of reporter plasmid supercoiling. The same plasmid also partially restored S. flexneri virulence gene transcription. These data show that overexpression of the S. flexneri topoisomerase IV genes can compensate for the loss of topoisomerase I in terms of general viability of the cell, DNA supercoiling, and (partially) virulence gene expression. The fact that S. flexneri does not exploit topoisomerase IV gene amplification as E. coli does points to a significant difference in the abilities of these species to adapt to the loss of topoisomerase I. PMID- 7783622 TI - Purification, characterization and mode of action of PdhR, the transcriptional repressor of the pdhR-aceEF-lpd operon of Escherichia coli. AB - The repressor of the pdhR-aceEF-lpd operon of Escherichia coli, PdhR, was amplified to 23% of total cell protein and purified to homogeneity by heparin agarose and cation-exchange chromatography. The purified protein is a monomer (M(r) 29,300) which binds specifically to DNA fragments containing the pdh promoter (Ppdh) in the absence of pyruvate. The pdh operator was identified by DNase I footprinting as a region of hyphenated dyad symmetry, +11AATTGGTaagACCAATT+27, situated just downstream of the transcript start site. In vitro transcription from Ppdh was repressed > 1000-fold by PdhR and this repression was antagonized in a concentration-dependent manner by its co effector, pyruvate. Studies on RNA polymerase binding at Ppdh showed that RNA polymerase protects the -44 to +21 region in the absence of PdhR, but no RNA polymerase binding or protection upstream of +9 could be detected in the presence of PdhR. It is concluded that PdhR represses transcription by binding to an operator site centred at +19 such that effective binding of RNA polymerase is prevented. PMID- 7783623 TI - The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence. AB - The Neisseria meningitidis haemoglobin receptor gene, hmbR, was cloned by complementation in a porphyrin-requiring Escherichia coli mutant. hmbR encodes an 89.5 kDa outer membrane protein which shares amino acid homology with the TonB dependent receptors of Gram-negative bacteria. HmbR had the highest similarity to Neisseria transferrin and lactoferrin receptors. The utilization of haemoglobin as an iron source required internalization of the haemin moiety by the cell. The mechanism of haemin internalization via the haemoglobin receptor was TonB dependent in E. coli. A N. meningitidis hmbR mutant was unable to use haemoglobin but could still use haemin as a sole iron source. The existence of a second N. meningitidis receptor gene, specific for haemin, was shown by the isolation of cosmids which did not hybridize with the hmbR probe, but which were able to complement an E. coli hemA aroB mutant on haemin-supplemented plates. The N. meningitidis hmbR mutant was attenuated in an infant rat model for meningococcal infection, indicating that haemoglobin utilization is important for N. meningitidis virulence. PMID- 7783624 TI - ComC is required for the processing and translocation of comGC, a pilin-like competence protein of Bacillus subtilis. AB - ComGC is a cell surface-localized protein required for DNA binding during transformation in Bacillus subtilis. It resembles type IV prepilins in its N terminal domain, particularly in the amino acid sequence surrounding the processing cleavage sites of these proteins. ComC is another protein required for DNA binding, which resembles the processing proteases that cleave type IV prepilins. We show here that ComGC is processed in competent cells and that this processing requires ComC. We also demonstrate that the PilD protein of Neisseria gonorrhoeae, a ComC homologue, can process ComGC in Escherichia coli, and that the ComC protein itself is the only B. subtilis protein needed to accomplish cleavage of ComGC in the latter organism. Based on NaOH-solubility studies, we have shown that in the absence of ComC, but in the presence of all other competence proteins, B. subtilis is incapable of correctly translocating ComGC to the outer face of the cell membrane. Finally, we show that ComGC can be cross linked to yield a form with higher molecular mass, possibly a dimer, and present evidence suggesting that formation of the higher mass complex takes place in the membrane, prior to translocation. Formation of this complex does not require ComC or any of the comG products, other than ComGC itself. PMID- 7783626 TI - Identification of cellular proteins involved in nikkomycin production in Streptomyces tendae Tu901. AB - Expression of genes involved in nikkomycin production in Streptomyces tendae was investigated by two-dimensional gel electrophoresis of cellular proteins. Ten gene products (P1-P10) were identified that were synthesized when nikkomycin was produced; these proteins were not detected in non-producing mutants. N-terminal sequences of six of the 10 proteins were obtained by microsequencing of protein spots excised from preparative two-dimensional gels. Protein P8 was identified as L-histidine amino-transferase (HisAT), which has been previously correlated with nikkomycin production. By using oligonucleotide probes deduced from the N terminal sequences of protein P2 and P6, we isolated an 8 kb BamHI fragment and a 6.5 kb PvuII fragment, respectively, from the genome of Streptomyces tendae Tu901. Restriction analyses revealed that both fragments overlapped within a region of 1.5 kb. Mapping of the oligonucleotide probe hybridizing sites indicated that the genes encoding protein P2 and P6 are closely spaced on the 8 kb BamHI fragment, and the latter is located on the overlapping region. DNA sequence analysis revealed that proteins P1 and P2 are encoded by a single gene, orfP1, that is translated at two initiation codons. The orfP1 gene was interrupted by homologous recombination using the integrating vector pWHM3. The gene-disrupted transformants did not produce nikkomycin, indicating that proteins P1 and P2 are essential for nikkomycin production. The data presented show that reverse genetics was successfully used to isolate genes involved in nikkomycin production. PMID- 7783625 TI - AmpD, essential for both beta-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase. AB - In enterobacteria, the ampD gene encodes a cytosolic protein which acts as a negative regulator of beta-lactamase expression. It is shown here that the AmpD protein is a novel N-acetylmuramyl-L-alanine amidase (E.C.3.5.1.28) participating in the intracellular recycling of peptidoglycan fragments. Surprisingly, AmpD exhibits an exclusive specificity for substrates containing anhydro muramic acid. This anhydro bond is mainly found in the peptidoglycan degradation products formed by the periplasmic lytic transglycosylases and thus might behave as a 'recycling tag' allowing the enzyme to distinguish these fragments from the newly synthesized peptidoglycan precursors. The AmpD substrate (or substrates) which accumulates in the absence of the corresponding enzymatic activity acts as an intracellular positive effector for beta-lactamase expression and might represent an element of a communication network between the chromosome and the cell wall peptidoglycan. PMID- 7783627 TI - Identification of phosphoproteins in Escherichia coli. AB - The substrates of ion- and lipid-stimulated protein kinase activity in extracts of Escherichia coli were purified by chromatography. Subsequent N-terminal sequencing suggests that these substrates include the following: a novel 80 kDa protein co-purifying with RNA polymerase but partially homologous to elongation factor G; a protein with an apparent molecular weight of 65 kDa identified as the ribosomal protein S1; and a 32 kDa protein identified as succinyl CoA synthetase, a key enzyme in the tricarboxylic acid cycle. The phosphorylation of these three proteins was markedly stimulated by the addition of manganese, and occurred on threonine, serine or tyrosine residues as indicated by the stability of the phosphoresidues during acid treatment. In addition, a calcium-stimulated protein of 70 kDa was identified as the heat-shock protein DnaK, and a 17 kDa lipid stimulated phosphoprotein as nucleotide diphosphate kinase. PMID- 7783628 TI - Group B streptococci adhere to a variant of fibronectin attached to a solid phase. AB - Group B streptococci (GBS) are the leading cause of neonatal pneumonia and meningitis. Adherence of GBS to host tissues may play an important role in the pathogenesis of infection. The host molecules which mediate GBS adherence to host tissues are unknown. Many bacterial pathogens adhere to fibronectin, an important component of the extracellular matrix (ECM). Some pathogens adhere to both immobilized and soluble fibronectin, while others adhere to immobilized fibronectin, but not to soluble fibronectin. Previous data indicated that GBS do not adhere to soluble fibronectin. We studied the ability of GBS to adhere to immobilized fibronectin. Forty-five per cent of the input inoculum of COH1, a virulent GBS isolate, adhered to fibronectin immobilized on polystyrene. COH1 did not adhere to the other ECM proteins tested (laminin, type I collagen, vitronectin, and tenascin). Nine out of nine GBS strains from human sources tested adhered specifically to fibronectin at levels varying from 4-60%. We considered the possibility that GBS were adherent to a contaminant in the fibronectin preparation. Properties of fibronectin, including the presence of an immunologic epitope of fibronectin and binding to collagen, were verified to be properties of the molecule to which GBS adhere. COH1 adhered to fibronectin captured by a monoclonal antibody to fibronectin (FN-15), confirming that the molecule to which GBS adhere bears immunologic determinants of fibronectin. Adherence of COH1 to fibronectin was inhibited by collagen, confirming that the molecule to which GBS adhere binds to collagen. These data strongly suggest that GBS adhere to fibronectin, and not to a contaminant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783629 TI - Homologies between salmolysin and some bacterial regulatory proteins. PMID- 7783630 TI - Na(+)-driven flagellar motors as a likely Na+ re-entry pathway in alkaliphilic bacteria. PMID- 7783631 TI - Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination. AB - An integron is a genetic unit that includes the determinants of the components of a site-specific recombination system capable of capturing and mobilizing genes that are contained in mobile elements called gene cassettes. An integron also provides a promoter for expression of the cassette genes, and integrons thus act both as natural cloning systems and as expression vectors. The essential components of an integron are an int gene encoding a site-specific recombinase belonging to the integrase family, an adjacent site, attI, that is recognized by the integrase and is the receptor site for the cassettes, and a promoter suitably oriented for expression of the cassette-encoded genes. The cassettes are mobile elements that include a gene (most commonly an antibiotic-resistance gene) and an integrase-specific recombination site that is a member of a family of sites known as 59-base elements. Cassettes can exist either free in a circularized form or integrated at the attI site, and only when integrated is a cassette formally part of an integron. A single site-specific recombination event involving the integron associated attI site and a cassette-associated 59-base element leads to insertion of a free circular cassette into a recipient integron. Multiple cassette insertions can occur, and integrons containing several cassettes have been found in the wild. The integrase also catalyses excisive recombination events that can lead to loss of cassettes from an itegron and generate free circular cassettes. Due to their ability to acquire new genes, integrons have a clear role in the evolution of the genomes of the plasmids and transposons that contain them. PMID- 7783632 TI - The twisted 'life' of DNA in the cell: bacterial topoisomerases. AB - DNA topoisomerases are essential to the cell for the regulation of DNA supercoiling levels and for chromosome decatenation. The proposed mechanisms for these reactions are essentially the same, except that a change in supercoiling is due to an intramolecular event, while decatenation requires an intermolecular event. The characterized bacterial topoisomerases appear capable of both types of reaction in vitro. Four DNA topoisomerases have been identified in Escherichia coli. Topoisomerase I, gyrase, and topoisomerase IV normally appear to have distinct essential functions within the cell. Gyrase and topoisomerase I are responsible for the regulation of DNA supercoiling. Both gyrase and topoisomerase IV are necessary for chromosomal decatenation. Multiple topoisomerases with distinct functions may give the cell more precise control over DNA topology by allowing tighter regulation of the principal enzymatic activities of these different proteins. PMID- 7783633 TI - Chlamydial envelope components and pathogen-host cell interactions. AB - Few bacterial pathogens are as widespread in nature or as capable of eliciting such a diversity of disease syndromes as are the chlamydiae. As obligate intracellular organisms, they pose a special research challenge in defining the molecular components and mechanisms for productive growth within host cells and the overall progress of infection throughout host tissue. Although a comprehensive view of chlamydial envelope composition and respective functions in pathogenesis is far from complete, ongoing investigations continue to expose new and intriguing avenues for exploration. PMID- 7783634 TI - Cloning and characterization of a Chlamydia psittaci gene coding for a protein localized in the inclusion membrane of infected cells. AB - Chlamydiae are obligate intracellular bacteria which occupy a non-acidified vacuole (the inclusion) throughout their developmental cycle. Little is known about events leading to the establishment and maintenance of the chlamydial inclusion membrane. To identify chlamydial proteins which are unique to the intracellular phase of the life cycle, an expression library of Chlamydia psittaci DNA was screened with convalescent antisera from infected animals and hyperimmune antisera generated against formalin-killed purified chlamydiae. Overlapping genomic clones were identified which expressed a 39 kDa protein only recognized by the convalescent sera. Sequence analysis of the clones identified two open reading frames (ORFs), one of which (ORF1) coded for a predicted 39 kDa gene product. The ORF1 sequence was amplified and fused to the malE gene of Escherichia coli and antisera were raised against the resulting fusion protein. Immunoblotting with these antisera demonstrated that the 39 kDa protein was present in lysates of infected cells and in reticulate bodies (RBs), but was at the limit of detection in lysates of purified C. psittaci elementary bodies. Fluorescence microscopy experiments demonstrated that this protein was localized in the inclusion membrane of infected HeLa cells, but was not detected on the developmental forms within the inclusion. Because the protein produced by ORF1 is deposited on the inclusion membrane of infected cells, this gene has been designated incA, (inclusion membrane protein A) and its gene product, IncA. In addition to the inclusion membrane, these antisera labelled structures that extended from the inclusion over the nucleus or into the cytoplasm of infected cells. Immunoblotting also demonstrated that IncA, in lysates of infected cells, had a migration pattern that seemed indicative of post-translational modification. This pattern was not observed in immunoblots of RBs or in the E. coli expressing IncA. Collectively, these data identify a chlamydial gene which codes for a protein that is released from RB and is localized in the inclusion membrane of infected cells. PMID- 7783635 TI - Structural identification of the lipo-chitin oligosaccharide nodulation signals of Rhizobium loti. AB - Rhizobium loti is a fast-growing Rhizobium species that has been described as a microsymbiont of plants of the genus Lotus. Nodulation studies show that Lotus plants are nodulated by R. loti, but not by most other Rhizobium strains, indicating that R. loti produces specific lipo-chitin oligosaccharides (LCOs) which are necessary for the nodulation of Lotus plants. The LCOs produced by five different Rhizobium loti strains have been purified and were shown to be N acetylglucosamine pentasaccharides of which the non-reducing residue is N methylated and N-acylated with cis-vaccenic acid (C18:1) or stearic acid (C18:O) and carries a carbamoyl group. In one R. loti strain, NZP2037, an additional carbamoyl group is present on the non-reducing terminal residue. The major class of LCO molecules is substituted on the reducing terminal residue with 4-O acetylfucose. Addition of LCOs to the roots of Lotus plants results in abundant distortion, swelling and branching of the root hairs, whereas spot inoculation leads to the formation of nodule primordia. PMID- 7783636 TI - The enterotoxin gene (cpe) of Clostridium perfringens can be chromosomal or plasmid-borne. AB - The location of the cpe gene, encoding the enterotoxin responsible for food poisoning in humans, has been studied in a series of enterotoxigenic Clostridium perfringens strains by means of pulsed field gel electrophoresis of genomic DNA. The cpe gene was found at the same chromosomal locus in strains associated with food poisoning in humans and was shown to be linked to a repetitive sequence, the HindIII repeat, and an open reading frame, ORF3, that may be part of an insertion sequence. In contrast, when the strains originated from domesticated livestock cpe was located on a large episome where it was often close to a copy of the transposable element IS1151. In these cases, the HindIII repeat was not linked to the cpe gene although this was generally preceded by ORF3. PMID- 7783637 TI - The bacteriophage T4 middle promoter PuvsX: analysis of regions important for binding of the T4 transcriptional activator MotA and for activation of transcription. AB - Bacteriophage T4 middle promoters, which are transcribed using phage-modified host RNA polymerase and the T4 transcriptional activator, MotA, match the host sigma 70 consensus sequence at -10, but they have a different consensus ((t/a)(t/a)TGCTT(t/c)A) (a MotA box) at -30. While the T4 middle promoter PuvsX has these -10 and -30 motifs, it also has matches to the MotA box at -35, -51, 70, and -87. We show that MotA binds to PuvsX DNA, footprinting a region that includes the MotA boxes at -30, -35, and -51. Very high levels of MotA are required for footprinting and gel-shift experiments, and protein-DNA complexes formed in the presence of both phage-modified polymerase and MotA are more resistant to HindIII cleavage than those formed with either protein alone. These results suggest that MotA-DNA interactions may be stabilized by phage-modified polymerase. Sequences between -18 and -38 are absolutely required for MotA activation of transcription, but sequences upstream of -38 are stimulatory, particularly when chloride instead of glutamate is the major anion. Our results dissect PuvsX into a core promoter, downstream of -38, which is required for MotA activation, and an upstream region that enhances transcription especially under conditions less favourable for protein-DNA interactions. PMID- 7783639 TI - Phosphorylation and functional analysis of PilA, a protein involved in the transcriptional regulation of the pilin gene in Neisseria gonorrhoeae. AB - The transcriptional regulation of the pilE gene, coding for the pilin in Neisseria gonorrhoeae, by PilA/PilB proteins is quite complex. Sequence analysis of PilA suggested that it has multiple domains. PilA appears to have in its N terminal half a DNA-binding site followed by a region showing sequence similarity with other bacterial transcriptional regulators. In its C-terminal half, PilA has extensive homology with the 54 kDa protein of the eukaryotic signal-recognition particle which is involved in protein secretion. A transcriptional fusion between the promoter of pilE and the lacZ gene was constructed and integrated into the gonococcal chromosome. We show that transcription of the pilE-lacZ fusion is affected in pilA mutants in the absence of any possible interference with pilin secretion. Moreover, pilE transcription depends on a -24/-12-type promoter which could be a member of a family of promoters recognized by the alternative sigma subunit, RpoN, of the RNA polymerase. We also show that PilA binds specifically to the promoter region of pilE and that it is phosphorylated in a manner dependent on acidic residues Glu-59, Asp-149 and Asp-186. The functional organization of PilA suggests that it may be an unusual transcriptional regulator different from other RpoN-dependent activators. PMID- 7783638 TI - Protective antigen-binding domain of anthrax lethal factor mediates translocation of a heterologous protein fused to its amino- or carboxy-terminus. AB - The edema factor (EF) and lethal factor (LF) components of anthrax toxin require anthrax protective antigen (PA) for binding and entry into mammalian cells. After internalization by receptor-mediated endocytosis, PA facilitates the translocation of EF and LF across the membrane of an acidic intracellular compartment. To characterize the translocation process, we generated chimeric proteins composed of the PA recognition domain of LF (LFN; residues 1-255) fused to either the amino-terminus or the carboxy-terminus of the catalytic chain of diphtheria toxin (DTA). The purified fusion proteins retained ADP ribosyltransferase activity and reacted with antisera against LF and diphtheria toxin. Both fusion proteins strongly inhibited protein synthesis in CHO-K1 cells in the presence of PA, but not in its absence, and they showed similar levels of activity. This activity could be inhibited by adding LF or the LFN fragment (which blocked the interaction of the fusion proteins with PA), by adding inhibitors of endosome acidification known to block entry of EF and LF into cells, or by introducing mutations that attenuated the ADP-ribosylation activity of the DTA moiety. The results demonstrate that LFN fused to either the amino terminus or the carboxy-terminus of a heterologous protein retains its ability to complement PA in mediating translocation of the protein to the cytoplasm. Besides its importance in understanding translocation, this finding provides the basis for constructing a translocation vector that mediates entry of a variety of heterologous proteins, which may require a free amino- or carboxy-terminus for biological activity, into the cytoplasm of mammalian cells. PMID- 7783640 TI - Localization of the start sites of lagging-strand replication of rolling-circle plasmids from gram-positive bacteria. AB - A number of small, multicopy plasmids from Gram-positive bacteria replicate by an asymmetric rolling-circle mechanism. Previous studies with several of these plasmids have identified a palindromic sequence, SSOA, that acts as the single strand origin (SSO) for the replication of the lagging-strand DNA. Although not all the SSOA sequences share DNA sequence homology, they are structurally very similar. We have used an in vitro system to study the lagging-strand replication of several plasmids from Gram-positive bacteria using the SSOA sequences of pT181, pE194 and pSN2 as representative of three different groups of Staphylococcus aureus plasmids. In addition, we have investigated the lagging strand replication of the pUB110 plasmid that contains an alternative single strand origin, SSOU. Our results confirm that RNA polymerase is involved in lagging-strand synthesis from both SSOA and SSOU-type lagging-strand origins. Interestingly, while initiation of lagging-strand DNA synthesis of pUB110 occurred predominantly at a single position within SSOU, replication of pT181, pSN2 and pE194 plasmids initiated at multiple positions from SSOA. PMID- 7783641 TI - A gene required for nutritional repression of the Bacillus subtilis dipeptide permease operon. AB - An insertion mutation was isolated that resulted in derepressed expression of the Bacillus subtillis dipeptide transport operon (dpp) during the exponential growth phase in rich medium. DNA flanking the site of insertion was found to encode an operon (codVWXY) of four potential open reading frames (ORFs). The deduced product of the codV ORF is similar to members of the lambda Int family; CodW and CodX are homologous to HsIV and HsIU, two putative heat-shock proteins from Escherichia coli, and to LapC and LapA, two gene products of unknown function from Pasteurella haemolytica. CodX also shares homology with a family of ATPases, including ClpX, a regulatory subunit of the E. coli ClpP protease. CodY does not have any homologues in the data-bases. The insertion mutation and all previously isolated spontaneous cod mutations were found to map in codY. In-frame deletion mutations in each of the other cod genes revealed that only codY is required for repression of dpp in nutrient-rich medium. The codY mutations partially relieved amino acid repression of the histidine utilization (hut) operon but had no effect on regulation of certain other early stationary phase-induced genes, such as spoVG and gsiA. PMID- 7783642 TI - The Pseudomonas aeruginosa pilK gene encodes a chemotactic methyltransferase (CheR) homologue that is translationally regulated. AB - A new locus, designated pilK, located immediately adjacent to the previously described Pseudomonas aeruginosa pilG-J gene cluster, has been identified. Sequence analysis of a 1.3 kb region revealed the presence of a single open reading frame of 291 amino acid residues (M(r) 33,338) that contained significant homology to the chemotactic methyltransferase proteins of Escherichia coli, Bacillus subtilis and the gliding bacterium Myxococcus xanthus. The 60 bp pilJ pilK intergenic region was devoid of promoter consensus sequences, suggesting that pilJ and pilK are contained within the same transcriptional unit. The intergenic region did contain, however, a large, highly GC-rich, inverted repeat that prevented PilK production in expression studies. To investigate the regulatory role of these sequences, pilK-lacZ gene fusions, as well as derivatives containing sequence alterations in the potential stem-loop region, were constructed and analysed in E. coli and P. aeruginosa. Modification of the inverted repeat region in pilK-lacZ protein fusion constructs resulted in as much as a 24-fold increase in beta-galactosidase activity, whereas similar modifications in pilK-lacZ transcriptional fusions had only a marginal effect on beta-galactosidase levels. These results indicated that PilK production may be largely regulated at the level of translation. In stark contrast to pilG-J mutants, which are dramatically impaired in pilus production and/or function, a PAO1 pilK deletion mutant was indistinguishable from the wild type. In addition, complementation studies suggested that the PilK and E. coli CheR proteins are not functionally interchangeable. PMID- 7783643 TI - Analysis of Vibrio cholerae ToxR function by construction of novel fusion proteins. AB - The ToxR protein is a transmembrane protein that regulates the expression of several virulence factors of Vibrio cholerae. Previous analysis of fusion proteins between ToxR and alkaline phosphatase (ToxR-PhoA) suggested that ToxR was active as a dimer. In order to determine whether dimerization of the ToxR periplasmic domain was essential for activity, this domain was replaced by monomeric and dimeric protein domains. Surprisingly, PhoA (dimeric), beta lactamase (monomeric, ToxR-Bla), or the leucine zipper of GCN4 (dimeric, ToxR GCN4-M) could substitute functionally for the ToxR periplasmic domain. ToxR-GCN4 fusion proteins, in which the ToxR transmembrane domain was eliminated (ToxR-GCN4 C), were inactive, but an additional fusion protein that contained a heterologous membrane-spanning domain retained activity. Strains containing each of these ToxR fusion proteins were analysed for in vivo colonization properties and response to in vitro growth conditions that are known to affect expression of the ToxR regulon. Strains containing ToxR-GCN4-M and ToxR-Bla responded like wild-type strains to in vitro growth conditions. In the infant-mouse colonization model, strains containing ToxR fusion proteins were all deficient in colonization relative to strains containing wild-type ToxR, and strains containing monomeric ToxR-Bla were most severely outcompeted. These results suggest that, under in vitro conditions, ToxR does not require a dimerized periplasmic domain, but that, under in vivo conditions, the correct conformation of the ToxR periplasmic domain may be more important for function. PMID- 7783645 TI - A 40 kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K-12 chromosome. AB - Many Salmonella typhimurium genes are required for bacterial entry into host cells. P22 transduction analysis has localized several invasion loci near minute 59 on the S. typhimurium chromosome. To further characterize the 59-60 min chromosomal region, we determined the physical and genetic map of 85 kb of S. typhimurium DNA between srl and cysC. It was previously shown that some of the invasion genes from this region are not present in Escherichia coli K-12. We examined whether other S. typhimurium genes on the 85 kb of DNA were similarly absent from E. coli. We found that a contiguous 40 kb fragment of the S. typhimurium chromosome which encodes invasion genes is absent from the corresponding region of the E. coli K-12 chromosome and may represent a 'pathogenicity island'. We speculate that acquisition of the 40 kb region must have significantly advanced the evolution of Salmonella as a pathogen. PMID- 7783644 TI - NolR controls expression of the Rhizobium meliloti nodulation genes involved in the core Nod factor synthesis. AB - The synthesis of Rhizobium meliloti Nod signal molecules, encoded by the nod gene products, is finely regulated. A negative control of plasmid-borne nod gene expression is provided by the NolR repressor encoded by the chromosomal nolR gene. NolR was previously shown to downregulate the expression of the activator nodD1 gene and the common nodABC operon by binding to an overlapping region of the two promoters adjacent to the n1 nod-box (Kondorosi et al., 1989). We demonstrate here that NolR also controls the expression of two additional genes, nodD2 and nodM, but does not directly regulate the expression of the host specific nod genes located downstream of the n2, n3 and n5 nod-boxes. Thus, the nod genes are differentially regulated by NolR and only those providing common nodulation functions, by determining the synthesis of the core Nod factor structure, are subjected to this negative regulation. Furthermore, NolR has a strong negative effect on the production of Nod metabolites, the level of which may serve as a fine-tuning mechanism for optimal nodulation, specific to host plant genotypes. In addition, it elicits preferential synthesis of Nod factors carrying unsaturated C16 fatty acids. Expression of nolR was high both in the free-living bacterium and in the bacteroid and it was downregulated by its own product and by the nod gene inducer luteolin. PMID- 7783646 TI - Requirement for FlhA in flagella assembly and swarm-cell differentiation by Proteus mirabilis. AB - Swarming by Proteus mirabilis is characterized by cycles of rapid population migration across surfaces, following differentiation of typical rods into long, aseptate swarm cells that overexpress flagella and virulence factors, particularly haemolysin. A non-swarming Tn5phoA mutant was unable to synthesize flagella, to fully elongate or to induce high levels of the toxin. The mutation lay within a 2091 bp gene encoding a homologue of the Escherichia coli FlhA belonging to a family of proteins that are required for assembly of flagella or virulence proteins and that are suggested to act either directly in membrane translocation and/or in regulating synthesis of the export apparatus. In trans expression of multicopy flhA restored cell elongation and migration and generated differentiation-specific hyperexpression of flagellin and toxin genes to levels above those seen in the wild-type strain. Transcription of flhA was strongly induced during differentiation, from its own putative sigma 28 promoter. The results suggest a mechanistic coupling of flagella assembly and swarm-cell differentiation. PMID- 7783648 TI - Hypotheses and the regulation of the bacterial cell cycle. PMID- 7783647 TI - Topological analyses of the L-fucose-H+ symport protein, FucP, from Escherichia coli. AB - The transport of L-fucose into Escherichia coli is mediated by the L-fucose-H+ symport protein (FucP). The fucP gene has been sequenced and encodes a hydrophobic protein that contains 438 amino acid residues, with a predicted M(r) of 47,773. The hydropathic profile of FucP indicates 10 to 12 hydrophobic regions that could span the membrane as alpha-helices. A 12-helix model with the N- and C termini located in the cytoplasm was derived from the hydropathic profile and from application of the 'positive inside' rule. This model was tested using beta lactamase fusion technology. Analyses of 62 different FucP-beta-lactamase fusions suggested that the FucP protein crosses the cytoplasmic membrane of E. coli 12 times, with the N- and C-termini in the cytoplasm. From measurements of [14C]-L fucose uptake, it was deduced that the last putative transmembrane region must be complete for transport activity to be retained and that the four C-terminal residues were unnecessary for transport activity. Fourier transform analyses show that all the predicted helices contain a periodicity that enables hydrophobic/hydrophilic faces to be identified; these were particularly evident in putative helices 1, 3, 4, 5, 6, 10 and 11. PMID- 7783649 TI - A tumor necrosis factor-beta polymorphism associated with hypertriglyceridemia in non-insulin-dependent diabetes mellitus. AB - Non-insulin-dependent (type II) diabetes mellitus is associated with significant abnormalities of lipoprotein metabolism. Control of glycemia rarely completely corrects the alterations in lipid metabolism, suggesting a participation of environmental and genetic factors. The observation that tumor necrosis factor (TNF) can modulate triglyceride metabolism offers a new genetic candidate to be analyzed. Samples of DNA from 91 control subjects and 61 diet-treated type II diabetic patients were analyzed to determine the lipid profile and a possible association with TNF genetic polymorphisms. For TNF restriction fragment length polymorphisms, we used the Nco I restriction enzyme and a TNF-alpha probe obtaining two allelic bands at 10.5 and 5.5 kb. We found a significant association (P < .01) of the 10.5-kb homozygous genotype in type II diabetic subjects with high triglyceride levels. Furthermore, these patients showed significant differences in triglycerides as compared with matched control subjects with the same genotype (P < .001). This study provides support for considering the TNF locus as a susceptibility genetic region in the hypertriglyceridemia of type II diabetes. PMID- 7783650 TI - Impaired nitric oxide release by glomeruli from diabetic rats. AB - Basal nitric oxide (NO) production and NO responses to carbamylcholine (CCh) and the Ca2+ ionophore A23187 were measured with a NO electrode in glomeruli isolated from 2 to 3-month-diabetic versus age-matched control rats. In the presence of CCh or A23187, NO production was markedly reduced in glomeruli from diabetic versus control rats. Spontaneous generation of NO by s-nitrosopenicillamine (SNAP) was also reduced in the presence of glomeruli from diabetic rats as compared with values either in control glomeruli or in buffer alone. The results demonstrate an impairment of NO generation and/or stability in glomeruli from 2 to 3-month-diabetic rats, which correlates with the previously observed suppression of NO-dependent glomerular cyclic guanosine 3',5'-monophosphate (cGMP) induced by diabetes. PMID- 7783651 TI - Human hepatic macrovesicular steatosis: a noninvasive study of mitochondrial ketoisocaproic acid decarboxylation. AB - Differentiating between alcoholic and nonalcoholic hepatic steatosis is often a difficult clinical task. However, decreased fatty acid mitochondrial oxidation appears as the main factor for alcoholic steatosis, whereas nonalcoholic steatosis may be due to other causes. We studied mitochondrial function, based on a 13C-ketoisocaproic acid (13C-KIC) breath test, in nine alcoholic and 12 nonalcoholic steatosis patients and 10 healthy volunteers. Our results showed a 42% 13C-KIC decarboxylation decrease in alcoholic steatosis patients, but not in nonalcoholic steatosis patients. This noninvasive breath test appears helpful for the diagnostic work-up of hepatic steatosis. PMID- 7783652 TI - Effect of kinesiologic recreation on plasma lipoproteins and apolipoproteins in fertile women. AB - The effect of physical exercise on lipid and apoprotein levels was studied in 31 healthy fertile women (mean age, 39.7 +/- 2.3 years) working as civil servants and leading a mostly sedentary way of life (group 1). A control group consisted of 31 age-matched women (mean age, 39.2 +/- 2.4 years) with a comparable life style (group 2). Group 1 performed physical exercise for at least 30 minutes three times per week. They also climbed a 500-m hill at least once per week. The study lasted 6 months, ie, from May to November 1990. Changes in maximum oxygen consumption (Vo2max), body weight, body mass index (BMI), waist to hip ratio (WHR), and levels of lipids and apolipoproteins (apos) A-1 and B were compared between the two groups of subjects. During the May-November period, the control group showed an increase in body weight (P < .02), total cholesterol, high density lipoprotein (HDL) cholesterol, HDL3, and low-density lipoprotein (LDL) cholesterol (P < .01) and a decrease in HDL2 (P < .05). In contrast, group 1 did not show any increase in total cholesterol, and their body weight decreased (P < .01). Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels decreased (P < .02), as did LDL cholesterol and HDL2 levels (P < .05), whereas HDL cholesterol and HDL3 levels increased (P < .01). There were no statistically significant changes in WHR and apo A-1 level. The findings indicated possible seasonal variations in lipoprotein levels in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783653 TI - Amylin-mediated reduction in insulin sensitivity corresponds to reduced insulin receptor kinase activity in the rat in vivo. AB - Studies were undertaken to elucidate further the mechanism whereby the pancreatic peptide amylin induces insulin resistance. Sixteen male Sprague-Dawley rats underwent hyperinsulinemic (14 pmol/kg/min, 0 to 120 minutes) euglycemic clamps in the presence or absence of amylin (500 pmol/kg/min, 60 to 120 minutes). Amylin induced insulin resistance at both the hepatic level (mean +/- SE: hepatic glucose output [HGO] with amylin 1.4 +/- 0.2 v without amylin -1.9 +/- 0.3 mmol/kg/h, P < .001) and peripheral level (glucose disposal [Rd] with amylin 5.0 +/- 0.2 v without amylin 8.5 +/- 0.6 mmol/kg/h, P < .001). Serum insulin levels were similar in the presence or absence of amylin alone (661 +/- 89 v 636 +/- 50 pmol/L, respectively, P = NS), but were significantly less when somatostatin (SRIF) was simultaneously infused (408 +/- 15 pmol/L, P < .02 v the other two groups). This suggests that endogenous insulin production was not suppressed by amylin under these study conditions. Similar findings were obtained in 18 animals in the absence of exogenous insulin infusion. In vitro kinase activity toward histone of skeletal muscle insulin receptors (IRs) activated by insulin in vivo was reduced in the presence of amylin to 6.0 +/- 0.8 versus 9.1 +/- 1.2 fmol phosphate into histone (insulin-infused) and 3.9 +/- 0.7 versus 6.9 +/- 1.4 (non insulin-infused; P < .03 by ANOVA). Serum calcium was significantly decreased in amylin-treated animals (1.93 +/- 0.04 v 2.30 +/- 0.05 mmol/L, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783654 TI - Factors affecting lipoprotein lipase in hypertensive patients. AB - Arterial hypertension is frequently associated with serum lipid abnormalities. Lipid metabolism can also be affected by antihypertensive treatment, possibly via an interference with lipoprotein lipase (LPL) activity. The aims of this study were to investigate the metabolic and hemodynamic factors that can interfere with plasma postheparin LPL activity in a sample of 13 patients with mild, uncomplicated arterial hypertension. The effects of vasodilator administration (prazosin and hydralazine) alone or in combination with a beta-blocker (propranolol) were also studied. A direct correlation between serum insulin levels and LPL activity was found during placebo treatment. This was confirmed by multiple regression analysis, which also showed a positive correlation of LPL activity with aortic flow velocity and plasma adrenaline (F significance = 0.0007, R2 = .905). Serum insulin was also directly correlated with cholesterol in high-density lipoproteins (HDLs) and in the HDL2 subfraction. A significant decrease in LPL activity was observed during the addition of propranolol to vasodilators as compared with vasodilators alone. A positive correlation was found between LPL and adrenaline changes induced by the combined treatment. These data suggest that LPL may play a role in the pathophysiologic connections between insulin action, the adrenergic nervous system (ANS), and lipid metabolism. PMID- 7783655 TI - Role of membrane transport in interorgan amino acid flow between muscle and small intestine. AB - In the fasting state, amino acids are released from the periphery to be used in splanchnic tissues. To understand the mechanism of such interorgan substrate exchange at the tissue level, we have determined the relationships between inward and outward amino acid transport and intracellular amino acid kinetics in the small intestine and skeletal muscle of postabsorptive anesthetized dogs. In the gut, amino acids appearing intracellularly (from inward transport, protein degradation, and absorption from the lumen) were used for protein synthesis more efficiently (P < .05) than in muscle (phenylalanine, 55% +/- 5% v 13% +/- 3%; lysine, 70% +/- 7% v 28% +/- 3%). In contrast, in muscle, amino acids appearing intracellularly (from inward transport and protein degradation) were preferentially (P < .05) released into the bloodstream, as opposed to being incorporated into protein (phenylalanine, 87% +/- 4%; lysine, 72% +/- 3%). Inward transport accounted for a greater (P < .05) proportion of total intracellular amino acid appearance in the gut than in muscle (leucine, 63% +/- 3% v 37 +/- 3%; valine, 75% +/- 5% v 53% +/- 3%; phenylalanine, 66% +/- 1% v 50% +/- 4%; lysine, 52% +/- 2% v 31% +/- 2%). We conclude that differences in transmembrane amino acid transport kinetics in both the inward and outward directions contribute to the net flow of amino acids from the muscle to the gut in the fasting state. PMID- 7783656 TI - Effect of short-term treatment with recombinant human growth hormone on lipids and lipoproteins in women and men without growth hormone disturbances. AB - The effect of recombinant human growth hormone (rHGH) on cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides (TG), apolipoprotein (apo) B, apo A-I, and lipoprotein(a) [Lp(a)] was studied in 40 postmenopausal women treated with 0.05, 0.1, or 0.2 IU/kg/d rHGH or placebo for 7 days. Cholesterol, LDL cholesterol, and HDL cholesterol decreased in a dose dependent manner (P = .001, P = .001, and P = .003, respectively), whereas apo B decreased insignificantly (P = .15). Apo A-I decreased significantly only among women treated with rHGH at a dose of 0.1 IU/kg/d (P = .03). When all rHGH-treated women were grouped together, Lp(a) increased (P = .001). We also studied 20 young men treated with either 0.2 IU/kg/d rHGH or placebo. As in women, cholesterol and apo B decreased P = .005 and P = .02, respectively), whereas Lp(a) increased (P = .05). There was no detectable effect of rHGH on TG concentrations in men. As in women, there was no significant effect of 0.2 IU/kg/d rHGH on apo A-I concentrations. All lipid and lipoprotein measures reached pretreatment levels during the first week after treatment was stopped, except Lp(a), which remained elevated 2 weeks after rHGH cessation. PMID- 7783657 TI - Glucocorticoids upregulate high-affinity, high-density lipoprotein binding sites in rat hepatocytes. AB - Glucocorticoid hormones (GL) regulate high-density lipoprotein (HDL) plasma concentrations by increasing synthesis and secretion of HDL by the liver. However, little is known about the effect of GL on the uptake and processing of HDL by hepatocytes (HEP). To investigate this question, we studied the effects of dexamethasone (DEX) on the expression of high-affinity HDL-binding sites via the specific binding and internalization of iodine-labeled apolipoprotein E (apo E) free HDL3 in a culture of rat HEP. Specific binding and internalization of HDL3 decreased by 60% in cells cultured in the absence of DEX for 48 hours. At concentrations of 10(-7) and 10(-5) mol/L, DEX prevented the decrease, maintaining specific binding and internalization versus the control level (at 24 hours). HDL-binding sites with a Kd of 20 micrograms/mL were revealed on the surface of cultured HEP. HEP demonstrated a greater binding capacity in the presence of DEX at concentrations of 10(-7) and 10(-5) mol/L (125 v 45 ng/mg cell protein). The effect of the hormone has demonstrated to be dose-dependent at concentrations between 10(-9) and 10(-7) mol/L, leveling off at 10(-7). Higher concentrations did not induce a further increase in specific binding and internalization. Withdrawal of the hormone from culture medium was associated with a decrease in specific binding of the ligand by 60% in the following 24 hours. To investigate the effect of glucocorticoid deficiency on liver uptake of HDL in vivo, specific binding and internalization were studied in a culture of HEP isolated from adrenalectomized rats (AER) at 2 hours after seeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783658 TI - Effect of combined administration of growth hormone (GH)-releasing hormone, GH releasing peptide-6, and pyridostigmine in normal and obese subjects. AB - Growth hormone (GH) secretion in response to all provocative stimuli is decreased in patients with obesity. Recently, we found that the combined administration of GH-releasing hormone (GHRH) and the hexapeptide GH-releasing peptide-6 (GHRP-6) induced a large increase in plasma GH levels. To gain further insight into the disrupted mechanism of GH regulation in obesity, we investigated whether the inhibition of somatostatinergic tone with pyridostigmine could further increase the GH response to combined administration of GHRH and GHRP-6. In normal subjects, administration of GHRH plus GHRP-6 induced a marked increase in plasma GH with a peak at 30 minutes (mean +/- SEM, 76.7 +/- 9.7 micrograms/L), which was similar to that obtained after pretreatment with pyridostigmine (74.7 +/- 9.4 micrograms/L). In obese patients, combined administration of GHRH plus GHRP-6 induced a clear increase in GH secretion with a peak at 15 minutes of 42.2 +/- 10.0 micrograms/L, which was also unaffected after pretreatment with pyridostigmine (38.4 +/- 5.8 micrograms/L). The GH response was lower in obese patients than in controls as assessed by the area under the curve after administration of both GHRH plus GHRP-6 (1,846 +/- 396 v 4,773 +/- 653, P < .01) and pyridostigmine plus GHRH plus GHRP-6 (1,989 +/- 372 v 5,098 +/- 679, P < .005). In conclusion, these data suggest that GHRP-6 can behave as a functional somatostatin antagonist, and that somatotrope responsiveness to the combined administration of GHRH plus GHRP-6 is largely independent of somatostatinergic tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783659 TI - Changes in plasma lipoprotein concentrations and composition in response to a low fat, high-fiber diet are associated with changes in serum estrogen concentrations in premenopausal women. AB - We have investigated the effects of a low-fat, high-fiber diet on plasma lipid and lipoprotein levels and serum sex hormone concentrations in 22 normal premenopausal women (mean age, 25.8 +/- 3.8 years). Participants consumed a baseline diet for 4 weeks (40% of calories as fat, 16% as saturated fatty acids, 8% as polyunsaturated fatty acids, 400 mg/d cholesterol, and 12 g/d dietary fiber) and then a low-fat, high-fiber diet for 8 to 10 weeks (16% to 18% of calories as fat, 4% as saturated fatty acids, 4% as polyunsaturated fatty acids, 150 mg/d cholesterol, and 40 g/d fiber). Blood samples for determination of plasma lipids and serum hormones were obtained during the follicular and luteal phases of the menstrual cycle during both diets. Compared with the baseline diet, the low-fat, high-fiber diet resulted in significant decreases in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations during both the follicular and luteal phases (TC, -14% and -16%; LDL cholesterol, -14% and -17%; and HDL cholesterol, -15% and -18%, respectively). During the follicular phase but not the luteal phase on the low-fat, high-fiber diet, women exhibited significant increases in plasma triglyceride ([TG] 22%) and very-low-density lipoprotein (VLDL)-TG (36%) concentrations. During the follicular phase, serum estrone sulfate concentrations decreased by 25% (P < .0001) when subjects were fed the low-fat, high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783660 TI - In vivo beta-cell function at the transition to early non-insulin-dependent diabetes mellitus. AB - Impaired insulin secretion occurs at some stage in the development of non-insulin dependent diabetes mellitus (NIDDM), possibly during impaired glucose tolerance (IGT) or early NIDDM. To assess insulin secretion at these critical stages, we measured the first-phase insulin response (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal glucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7.8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and insulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although as a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired insulin secretion. The first-phase response to glucose was markedly reduced in absolute terms (P < .001), but all secretion indices were impaired relative to the degree of insulin resistance (P = .05 to P < .0001). These results suggest that in Pima Indians, impairment of insulin secretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, seems intact, although a subtle defect in the first-phase insulin response to glucose could not be ruled out in this study. Glucose sensing for first-phase secretion may be one of the early secretory defects in the progression of glucose intolerance and seems to be critical at the transition from IGT to early NIDDM. PMID- 7783661 TI - Short-term changes in energy metabolism after 1 month of a regular oral diet in severely malnourished cirrhotic patients. AB - Malnutrition in patients with liver cirrhosis is currently associated with abnormal fuel metabolism. The aim of this study was to evaluate changes in energy production and substrate oxidation rates in a group of 26 nonanorectic severely malnourished cirrhotic patients in stable clinical condition after 1 month of an oral diet. Child-Pugh score, nutritional status, energy expenditure, rates of nutrient oxidation, and plasma levels of intermediary metabolites in the postabsorptive phase were assessed before and after 1 month of oral nutrition. Upon entry onto the study, caloric and protein intakes were 40.1 +/- 2.0 kcal/kg and 1.44 +/- 0.8 g/kg, respectively. The Child-Pugh score did not change during the study, whereas nutritional status improved as shown by increased muscular midarm circumference, ([MMAC] P < .02), height-creatinine index (P < .05), triceps skinfold thickness ([TST] P < .01), and fat mass (P < .001). Inflammatory state improved during the study, as shown by the decrease of C-reactive protein ([CRP] P < .01) and orosomucoid (P < .001). The ratio of caloric intake to resting energy expenditure (REE) increased (1.53 +/- 0.06 v 1.66 +/- 0.07, P < .05), as well as the rate of glucose oxidation ([Gox] 73.6 +/- 9.9 v 128.1 +/- 10.3 mg/min, P < .001) and urine nitrogen excretion (6.69 +/- 0.47 v 7.96 +/- 0.48 g/d, P < .02). On the other hand, the rate of lipid oxidation (Lox) decreased (67.3 +/- 3.9 v 47.3 +/- 4.9 mg/min, P < .001) and was correlated with the decrease of free fatty acid (FFA) levels (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783662 TI - Tissue-specific alterations in G protein expression in genetic versus diet induced models of non-insulin-dependent diabetes mellitus in the mouse. AB - Various tissues were obtained from the well-characterized genetic model (C57BL/6J ob/ob) of non-insulin-dependent diabetes mellitus (NIDDM) and from a diet-induced model of NIDDM produced in the same genetic background (C57BL/6J). The objectives were to determine whether the previously observed changes in guanine nucleotide binding regulatory protein (G protein) expression in adipose tissue from ob/ob mice were mirrored by concomitant changes in other tissues, and whether NIDDM of a different etiology would share similar alterations in G protein expression. Plasma membranes from adipocytes, brain, heart, liver, and testes were probed with alpha-subunit-specific antisera, and the level of G protein expression in each model was compared with that in its lean littermate control. Adipose, heart, and liver cell membranes from ob/ob mice contained significantly less alpha subunit of stimulatory G protein (Gs alpha) than those from their lean littermates. As compared with the lean littermates, heart alpha-subunit-2 of inhibitory G protein (Gi alpha-2), liver Gi alpha-3, and adipocyte G1 alpha-1 and Gi alpha-3 were also reduced in ob/ob mice. In contrast, Gi alpha-2 and Go alpha were increased over lean-control levels in brain tissue from ob/ob mice, whereas Gs alpha was unchanged. G protein expression in the testes did not differ between lean and ob/ob mice. In the diet-induced model of NIDDM, Gs alpha expression in the liver was twofold greater in obese/diabetic mice as compared with lean controls. However, G protein expression in all other tissues examined did not differ between obese/diabetic animals and lean littermates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783664 TI - Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus. AB - Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myocytes for lipoprotein triglyceride oxidation. In human obesity, an insulin-resistant state, SMLPL levels measured in the fasted state are either decreased or unchanged as compared with levels in normal-weight controls. However, insulin/glucose infusion increases SMLPL activity in obese individuals, whereas in normal-weight subjects the activity is decreased. One of the goals of this study was to determine the impact of obesity with concomitant non-insulin-dependent diabetes mellitus (NIDDM) on fasting SMLPL and on the change in SMLPL activity (delta MLPL) in response to an insulin/glucose infusion. Because NIDDM is often a more insulin resistant state, it was hypothesized that SMLPL activity would be further increased by insulin/glucose in subjects who were obese and had NIDDM. Measurements of SMLPL were made from biopsies of vastus lateralis skeletal muscle taken before and after a 6-hour insulin/glucose infusion in the setting of a euglycemic clamp. Thirteen nondiabetic obese women (OBC) and six nondiabetic normal-weight women (NWC) were used as control subjects. SMLPL levels measured in the fasted state were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calculation of the mean glucose infusion rate (GIR) required to sustain euglycemia over the last 60 minutes of the infusion. For all three groups combined, representing a continuum of insulin sensitivity, there was a positive correlation between GIR and fasting SMLPL. As described earlier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after insulin/glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783663 TI - Ethanol as a xanthine dehydrogenase inhibitor. AB - In the present study, we investigated whether ethanol inhibits the activity of xanthine dehydrogenase. Ethanol and/or inosine were administered to normal subjects, and plasma concentration and urinary excretion of purine bases were measured together with blood concentrations of lactic acid and pyruvic acid. In addition, ethanol and pyrazinamide were administered to these subjects, and plasma concentration and urinary excretion of pyrazinamide and its major metabolites were measured. Increases in plasma concentration and urinary excretion of xanthine induced by a combination of ethanol and inosine were greater than the sums of increases induced separately by ethanol and inosine, although increases in plasma concentration and urinary excretion of uric acid induced by the combination of ethanol and inosine were not different from the sums of increases induced separately by ethanol and inosine. Ethanol increased the ratio of blood lactic acid to blood pyruvic acid and decreased plasma concentration and urinary excretion of 5-hydroxypyrazinamide and 5 hydroxypyrazinoic acid. These results suggest that ethanol inhibits xanthine dehydrogenase presumably by an ethanol-induced increase in the cytosolic concentration of NADH in the liver. PMID- 7783665 TI - Na+/H+ exchanger isoform-1 abundance in skin fibroblasts of type I diabetic patients with nephropathy. AB - In diabetic nephropathy and essential hypertension, the cellular Na+/H+ exchanger (NHE) exhibits increased activity. Whether this reflects increased numbers of NHE isoform-1 (NHE-1) transporters or increased turnover per molecule has not been established. We have used a specific polyclonal antibody directed toward the C terminal of NHE-1 to measure NHE-1 content in cultured skin fibroblasts from diabetic patients with (DN) and without (DCON) nephropathy and normal controls (CON). NHE-1 content in fibroblasts from DN subjects was significantly less than that in the other two groups. This suggests that increased NHE activity in diabetic nephropathy is attributed to increased NHE-1 turnover per site rather than increased NHE-1 expression. PMID- 7783666 TI - Sorbitol malabsorption and nonspecific abdominal symptoms in type II diabetes. AB - Some data suggest that sorbitol intake may be responsible for diarrhea in diabetic patients. One hundred thirteen hydrogen breath tests were performed in type II diabetics (72) and normal controls (41) after oral loads of sorbitol ranging from 2.5 to 20 g in iso-osmolar solutions to assess the role of malabsorption of this compound in the genesis of abdominal symptoms. The prevalence of sorbitol malabsorption and abdominal symptoms, peak (Cmax H2) and total (Ctot H2) hydrogen production, and mouth to cecum transit time (MCTT) did not differ in type II diabetics and controls. Malabsorption was observed more frequently with the highest doses of sorbitol (10% of patients at a dose of 2.5 g and approximately 75% at 20 g). Symptoms, usually consisting of mild discomfort and abdominal distension, were observed only after sorbitol loads of 10 and 20 g in 27.2% of the diabetics and in 36.3% of the controls. Diarrhea was present in three subjects (two diabetics and one control) only at a dose of 20 g. These data indicate that it is highly unlikely for sorbitol to play a role in inducing diabetes diarrhea. A moderate (up to 10 g) sorbitol intake is not contraindicated in type II diabetics. PMID- 7783667 TI - Fish oil enhances macrophage tumor necrosis factor-alpha mRNA expression at the transcriptional level. AB - Dietary supplementation with fish oil has previously been shown to enhance in vivo and in vitro (macrophage) synthesis of tumor necrosis factor-alpha (TNF alpha) in response to bacterial lipopolysaccharide (LPS) stimulation. The studies reported here were conducted to gain insight into the molecular mechanisms of this nutrient-immune interaction by comparing the concentration, rate of synthesis, and rate of decay of TNF-alpha mRNA upon LPS stimulation of macrophages obtained from mice fed high-fat diets, rich in either fish oil, corn oil, or coconut oil, or a low-fat diet for a period of 4 weeks. The results indicate that compared with the other diet groups, LPS stimulation of macrophages from mice fed fish oil resulted in (1) enhanced levels of mRNA and protein for TNF-alpha, and (2) increased transcription of TNF-alpha mRNA as assessed by nuclear run-on assays. Posttranscriptional studies showed that the rate of decay of TNF-alpha mRNA did not vary significantly for macrophages from mice fed with fish oil as compared with corn oil. Further studies using actinomycin D and cycloheximide suggested that RNA synthesis, but not protein synthesis, was necessary for TNF-alpha mRNA accumulation. Taken together, the present studies suggest that fish oil enhances macrophage TNF-alpha mRNA expression at the transcriptional level. Although such TNF-alpha upregulation may provide a mechanism for the beneficial effects of fish oil in certain inflammatory and immune disorders, it can also underlie its potential deleterious effects if the degree of upregulation leads to exaggerated TNF-alpha production that exceeds the limits of benefit to reach toxic levels. PMID- 7783668 TI - Abnormal arachidonate distribution in low-density lipoprotein and thoracic aorta in hyperinsulinemia. AB - The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension (20 U/kg) for 12 weeks. After this period, body mass and food consumption did not differ significantly between control and insulin-treated animals. Daily insulin injection significantly increased urinary excretion of epinephrine and decreased urinary excretion of norepinephrine and dopamine, but had no significant effect on blood pressure or heart rate. Although insulin decreased plasma triglyceride concentration by 44% (P < .01), the triglyceride to protein ratio in plasma low density lipoprotein (LDL) was increased by 34% (P < .05) in insulin-treated rats; the cholesterol to protein and triglyceride to protein ratios remained unaffected, indicating a change in the quality of the LDL particle. Insulin also increased the percentage of arachidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contrast, cholesteryl esters and triglycerides in the thoracic aorta were significantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and decreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmitoleic acid (16:1) and decreased the percentages of saturated fatty acids and n-6 fatty acids in aortic cholesteryl esters. These results indicate that insulin induced deposition of cholesteryl esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data further suggest that the development of atherosclerosis in response to hyperinsulinemia may be associated with arachidonate-rich triglycerides in LDL. PMID- 7783669 TI - Adaptations in glucose homeostasis during chronic nutritional deprivation in rats: hepatic resistance to both insulin and glucagon. AB - The role of glucagon in glucose homeostasis during chronic malnutrition was studied in weanling-littermate rats either fed ad libitum or restricted to 60% of ad libitum intake for 8 weeks. Fasting glucose and insulin levels were lower in malnourished rats, and their response to glucagon (0.02 mg/kg intravenous [IV]) after a 16-hour fast was significantly less than in control littermates for both glucose (P = .039) and insulin (P = .008). During euglycemic glucose clamp studies at identical plasma glucose (PG) levels, insulin suppression of hepatic glucose production (HGP) was impaired in malnourished rats, indicating insulin resistance (mean +/- SE HGP: 48 +/- 5 v 32 +/- 10 mumol.kg-1.min-1 for controls, P = .028). Glucose disposal was not significantly different in the two groups. However, after IV glucagon, the increase in HGP was markedly impaired in malnourished rats (P = .0004), with the total amount of glucose produced by the liver over 15 minutes being 1,397 +/- 114 mumol/kg as compared with 2,031 +/- 118 in controls (P = .0047). The impaired response was not due to defective glycogenolysis, because the release of glucose from prelabeled glycogen in response to glucagon injection contributed only 6% to 8% of the overall increase in glucose output from the liver, and was not different in the two groups. Furthermore, liver glycogen stores were virtually exhausted after the 16-hour fast, without glucagon injection. Glucagon receptor affinity and number were not affected by malnutrition. It is concluded that (1) chronic malnutrition is associated with hepatic resistance to both insulin and glucagon, (2) the glucagon resistance is not due to impaired glycogenolysis, and (3) it is mediated by a postreceptor defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783671 TI - The Michigan physician today. Results of the MSMS survey on practice characteristics. Executive summary. PMID- 7783670 TI - AMA, state medical societies launch "litigation center". PMID- 7783672 TI - Virus activation by host proteinases. A pivotal role in the spread of infection, tissue tropism and pathogenicity. PMID- 7783673 TI - Isolation and characterization of bile acid 7-dehydroxylating bacteria from human feces. AB - Methods for isolation of fecal 7 alpha-dehydroxylating bacteria are presented. A total of 219 strains were isolated from feces of healthy humans, and their ability to 7-dehydroxylate cholic, chenodeoxycholic, and ursodeoxycholic acids were examined. Of all the isolates, 14 strains were found to be capable of eliminating the hydroxy group at C-7 alpha and/or C-7 beta. All the isolates were strictly anaerobic, Gram-positive rods. Thirteen isolates were non-sporeforming bacteria showing certain saccharolytic properties with the production of acid and gas from dextrose, and were catalase-positive but indole-, lecithinase-, urease- and oxidase-negative. Based on the data available at present, it was concluded that they could be regarded as members of the genus Eubacterium. One strain, however was identified as Clostridium sordellii. The isolated strains capable of 7 alpha-dehydroxylating cholic acid and chenodeoxycholic acid were also able to oxidize the hydroxy group at C-7 alpha. Nine strains (10, 12, 36S, M-2, M-17, M 18, Y-98, Y-1112, and Y-1113) of the 7 alpha-dehydroxylating bacteria were confirmed to have 7 beta-dehydroxylation ability, but five strains (O-51, O-52, O 71, O-72, and Y-67) could not transform ursodeoxycholic acid to lithocholic acid. PMID- 7783674 TI - Molecular cloning of the leuB gene from Bacteroides fragilis by functional complementation in Escherichia coli. AB - Clones containing the Bacteroides fragilis leuB-complementing gene were isolated by screening of a B. fragilis genomic library constructed in Escherichia coli. One recombinant clone, designated pOT865, with the smallest DNA insert (4.5 kb) could complement three independent leuB mutations in E. coli and the leuB complementing determinant in pOT865 was localized to a region of 1.5-kb DNA. The results of Southern blot analysis suggested that a single copy of the cloned gene was present in the B. fragilis genome. The cloned fragment appeared to contain a sequence that could function as promoter in E. coli and direct the synthesis of a 42-kDa protein. These results suggest that the cloned segment contains the structural gene for beta-isopropylmalate dehydrogenase (leuB). PMID- 7783675 TI - Purification and characterization of metallo-beta-lactamase from Serratia marcescens. AB - Carbapenem-hydrolyzing beta-lactamase from Serratia marcescens FHSM4055 was purified 926-fold by means of carboxylmethyl Sephadex C-50, Sephacryl S-200, and Mono S column chromatography. The molecular weight was 30,000 by SDS-PAGE and the isoelectric point was 8.7. The enzyme activity was inhibited by EDTA, and restored by adding zinc (II) or manganese (II). It was inhibited by p chloromercuribenzoate and iodine as well as the heavy metals, Hg (II), Fe (II), Fe (III), and Cu (II). These results indicate that the enzyme is a metallo-beta lactamase and that the SH-group of only one cysteine residue probably binds to the metal ion, thus contributing to the stability of the enzyme active center. The specific constant (kcat/Km) showed that the enzyme hydrolyzed various beta lactam antibiotics such as carbapenems, cephalosporins, moxalactam, cephamycins, and penicillins other than monobactams. Ampicillin and piperacillin with respective amino- and imino-groups, ceftazidime with a carboxypropyloxyimino group, and cefclidin with a carbamoylquinuclidine-group were poor substrates among the beta-lactam antibiotics other than the monobactams tested. The plots of the turnover number (kcat) against pH for the hydrolysis of cephaloridine gave an asymmetrical curve with the 'tail' on the acid side (pK1, 5.9; pK2, 9.0; pK3, 10.8), whereas those of kcat/Km gave a bell-shaped curve (pK1, 5.8; pK2, 9.8). Both results suggest that two ionic forms of an intermediate yield the same product at different rates and that the enzyme is stable under alkaline conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783676 TI - Characterization of the mode of Hantaan virus infection in adult mice using a nested reverse transcriptase polymerase chain reaction: transient virus replication in adult mice. AB - A polymerase chain reaction (PCR) for the detection of hantavirus genome was established and applied to analyze the mode of infection of Hantaan virus in adult ICR mice. The cDNA for the S genome segment of Hantaan virus was reverse transcribed from the total RNA of organs of the infected mice. The sequence in the S genome segment of Hantaan virus was successfully amplified by reverse transcriptase (RT)-PCR followed by nested PCR. In 5-week-old ICR mice inoculated intraperitoneally with Hantaan virus, strain 76-118 (1.3 x 10(5) FFU/mouse), the virus was detected in clots and lungs from 3 to 10 days post-inoculation (p.i.) by nested PCR and virus-isolation techniques. No virus was detected in any specimens collected on 1 day and after 28 days p.i., and in spleens and brains through the observation period by both methods. The antibody which was measured by indirect immunofluorescence antibody assay (IFA) appeared at 7 days p.i. and the geometric mean titer was elevated to its maximum level of 1:203 at 10 days p.i., maintaining the same level until 35 days p.i. These results suggest that adult mice are transiently infected with Hantaan virus. PMID- 7783677 TI - Analysis of cellular response and gamma interferon synthesis in bronchoalveolar lavage fluid and lung homogenate of mice infected with Pneumocystis carinii. AB - The cellular and cytokine responses in the lungs of mice infected with Pneumocystis carinii were examined on both lung homogenates and bronchoalveolar lavage (BAL) fluids. In the lungs of infected mice, the number of P. carinii cysts rapidly decreased by day 7, then started to increase with a peak on day 14, and thereafter decreased gradually. When the presence of P. carinii was examined at the DNA level by dot blot hybridization, a similar clearance curve was obtained, and the organisms were shown to be completely eliminated on day 28. In the late phase of infection, leukocytes, mainly lymphocytes, increased in number when analyzed on lung homogenates, while no significant increase of inflammatory cells was observed in BAL fluids. An accumulation of both CD4+ and CD8+ T cells and an increase of activated T cells expressing IL-2R alpha were observed in lung homogenates of the infected mice. In addition, a considerable amount of IFN-gamma was detected in lung homogenates, but not in BAL fluids. These data indicate that lung homogenates are more suitable than BAL fluids for the analysis of cellular and cytokine responses in the lungs of mice infected with P. carinii. To define the involvement of IFN-gamma in host defense against P. carinii, the effect of this cytokine on the killing activity of macrophages against P. carinii was examined in vitro. IFN-gamma was found to augment this activity by increasing nitric oxide synthesis of the macrophages. Thus, it is suggested that IFN-gamma plays an important role in the protection of mice from P. carinii infection. PMID- 7783678 TI - Comparison of a reversed passive latex agglutination and a polymerase chain reaction for identification of cholera toxin producing Vibrio cholerae O1. AB - Production of cholera toxin (CT) in AKI medium and conservation of CT gene (ctx) of 49 strains of Vibrio cholerae O1 were compared by reversed passive latex agglutination (RPLA) and polymerase chain reaction (PCR). The production of CT agreed with conservation of the ctx in 48 out of the 49 strains. Ten strains were positive, and 38 strains were negative by both methods. Only one strain was negative in RPLA and positive in PCR. This suggested that the combination of AKI SW and RPLA is comparable to PCR to identify CT-producing V. cholerae O1. PMID- 7783679 TI - Serological studies of the antigenic similarity between typhus group rickettsiae and Weil-Felix test antigens. AB - The sera from two patients with murine typhus reacted with whole cells of Rickettsia prowazekii, R. typhi, and Proteus vulgaris OX19, and with lipopolysaccharides (LPS) from the spotted fever group rickettsia strain TT-118 and P. vulgaris OX19 in the enzyme-linked immunosorbent assay. Sera from these patients reacted with ladder-like bands of LPS from R. prowazekii and R. typhi in the immunoblot, whereas the reactivity of these sera with LPS from P. vulgaris OX19 differed from each other. These results indicate that LPS from the typhus group rickettsiae and P. vulgaris OX19 contain similar epitopes. PMID- 7783680 TI - Production of antigenically related exocellular elastolytic proteases mediating hemagglutination by vibrios. AB - Exocellular proteases produced by Vibrio fluvialis, V. furnissii, V. metschnikovii and V. campbellii were characterized and compared to those of V. mimicus protease (VMP) and V. vulnificus protease (VVP). These proteases possessed both elastolytic and hemagglutinating abilities and were identified, except that of V. metschnikovii, as metalloprotease. Conversely, V. metschnikovii protease failed to exhibit some of the salient features for metalloproteases suggesting the existence of protease(s) other than metalloprotease. However, antibodies against VVP cross-reacted to these proteases and to VMP indicating antigenic relatedness amongst vibrio proteases. This study, thus, demonstrated the prevalent distributions of antigenically related proteases both in pathogenic and non-pathogenic vibrios, bringing their status as a virulence determinant into question. PMID- 7783681 TI - Experimental dental caries on gnotobiotic inbred mice. AB - The purpose of this study in mono-infected gnotobiotic BALB/cA and C3H/HeN mice was to evaluate the cariogenicity of Enterococcus faecalis. The caries incidence and mean caries score in the BALB/cA mice were significantly higher than those in the C3H/HeN. In both of the mouse strains, the mean number of E. faecalis isolated from the cecum content was almost the same, however, the mean number of E. faecalis from the maxilla of BALB/cA was significantly higher than that of C3H/HeN. These results indicate that C3H/HeN has some factors that prevent E. faecalis from attaching to the tooth surfaces. PMID- 7783682 TI - A gene encoding a cytochrome c oxidase-like protein is located closely to the cytochrome c-553 gene in the anaerobic bacterium, Desulfovibrio vulgaris (Miyazaki F). AB - The gene encoding cytochrome c-553 from Desulfovibrio vulgaris (Miyazaki F) was cloned using a synthetic oligodeoxyribonucleotide probe. The nucleotide sequence indicated that cytochrome c-553 was synthesized as a precursor protein with an NH2-terminal signal sequence of 23 residues. In the cloned DNA fragment, there are three other open reading frames whose products have 191, 157, 541 amino acid residues, respectively. The putative ORF-4 product is highly homologous with the cytochrome c oxidase subunit I from various organisms. PMID- 7783683 TI - Carbohydrate-dependent biological activities of glycosylated human interferon beta on human hepatoblastoma cells in vitro. AB - To evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-beta, Chinese hamster ovary cell-derived glycosylated recombinant human interferon-beta and Escherichia coli-derived unglycosylated recombinant human interferon-beta were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon-beta expressed more cell-growth inhibitory action, 2'5'-oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon-betas. These results showed that the sugar chain structure of human interferon-beta affects its biological activity on human hepatoblastoma cells. PMID- 7783684 TI - Influence of exogenous interleukin-2 concentration on the isolation of human immunodeficiency virus. AB - A significant increase (P = 0.015) in the HIV isolation rate from plasma samples was achieved by use of 10 U/ml exogenous interleukin-2 compared to 20 U/ml. The sensitivity rose from 0% to 29% in patients negative for p24 core antigen (P = 0.031) and from 71% to 86% in patients positive for p24 core antigen in plasma (P > 0.05). Titration of infectious HIV revealed that 10 U/ml interleukin-2 is the optimal concentration to isolate low numbers of infectious particles of HIV. PMID- 7783686 TI - T cell-dependent activation of macrophages and enhancement of their phagocytic activity in the lungs of mice inoculated with heat-killed Cryptococcus neoformans: involvement of IFN-gamma and its protective effect against cryptococcal infection. AB - Previous investigations have demonstrated that macrophages play a critical role in the first-line cellular defense mechanism against infection with Cryptococcus neoformans. In the present study, to elucidate the way in which anticryptococcal activity of macrophages is regulated at the site of infection, pulmonary intraparenchymal macrophages were directly analyzed for expression of their surface molecules and their phagocytic activities against the organism, and the effects of depletion of T cells and endogenous IFN-gamma in vivo on these parameters were examined. In the lungs of mice intratracheally inoculated with heat-killed C. neoformans, macrophages were activated, as indicated by augmented expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1) and Fc receptor (FcR), and about two-thirds of macrophages were found to have ingested an average of 3.77 +/- 0.12 yeast cells per macrophage. In mice depleted of both CD4+ and CD8+ T cells by injecting the specific monoclonal antibodies (mAbs) or anti-IFN-gamma mAb, not only augmentation of the expression of macrophage activation markers but also phagocytosis of C. neoformans was significantly reduced. These results suggest that anticryptococcal activity of macrophages is regulated by IFN-gamma endogenously produced by T cells. Additionally, treatment with IFN-gamma were shown to significantly prolong the survival time of mice infected with viable C. neoformans. Additionally, preimmunization with heat killed C. neoformans significantly prolonged the survival time of mice which received the following infection. PMID- 7783685 TI - CD3+/TCR-alpha beta- cells are important in protecting spinal cord tissues against Theiler's virus strain GD VII infection. AB - Intravenous infection with Theiler's virus strain GD VII causes acute encephalomyelitis in mice. Endogenous IFN-gamma produced in the spinal cord is important to protect the tissue in mice infected with this virus. Neither CD4+ cells nor CD8+ cells infiltrated the spinal cords of infected mice until Day 9 postinfection. However, the number of CD3+/TCR-gamma delta+ cells increased in the spinal cords of mice infected with the virus. These cells resided in the spinal cords of normal mice, and produced IFN-gamma as a result of stimulation by immobilized anti-CD3 mAb. Elimination of CD3+ cells by the administration of a specific mAb augmented viral replication and suppressed production of endogenous IFN-gamma. Depletion of TCR-alpha beta+ cells and ASGM1+ cells did not affect the viral replication, and did not alter the production of IFN-gamma. Therefore, CD3+/TCR-alpha beta- cells producing IFN-gamma play an important role in the protection of the spinal cord against Theiler's virus infection. These results suggest that CD3+/TCR-alpha beta- cells might be identical to TCR-gamma delta+ cells. PMID- 7783687 TI - C3d and Epstein-Barr virus (CR2/CD21 ligands) stimulate cells of an HTLV-I line, MT-2. AB - We studied the physiological role of complement receptor type II (CR2, C3d/EBV receptor) expressed on T cells using MT-2 cells. First, we confirmed CR2 expression on MT-2 cells by flow cytometry and found that the MW of CR2 molecules on these cells and Raji B cells were the same by SDS-PAGE analysis. When MT-2 lysates were incubated with anti-CR2 mAb HB5 and thereafter with 32P-labeled ATP, 52- and 74-kDa proteins were phosphorylated, suggesting the activation of MT-2 cells through the complex of CR2 with these proteins. In this respect, we measured lymphotoxin production by MT-2 cells when incubated with C3d or EBV. The cytotoxicity of the MT-2 supernatant against L929 cells was elevated in a dose- and time-dependent manner. Next, we confirmed EBNA expression on EBV-infected MT 2 cells and attempted to establish an EBV-positive MT-2 clone by in vitro EBV infection. However, these clones disappeared during cloning. To clarify this mechanism, we examined the EBV genome in MT-2 cells. By Southern blot analysis, BamHI digestion of DNA extracts from MT-2 cells 3 days after EBV treatment gave a 3.0-kb signal which comigrated with the EBV BamHI-W probe. The 3.0-kb signal of genomic EBV-DNA was detected at 1, 2, 3, 5, and 7 days after EBV treatment, but could not be detected at 14 days. Thus, natural ligands of CR2 stimulate CR2 positive MT-2 cells through their functionally active CR2 molecules and in vitro EBV infection of MT-2 cells might be transient. PMID- 7783688 TI - Conspicuous growth of intravenously inoculated Staphylococcus aureus in subcutaneously established Ehrlich ascites tumor tissue of mice. AB - Intratumoral growth of Staphylococcus aureus was compared with the intrarenal growth, to examine the usefulness of the method as a marker of its pathogenicity. When 5 x 10(7) CFU/mouse of three derivatives from S. aureus Cowan I with different intrarenal growth were intravenously injected into Ehrlich tumor bearing mice, they lodged in the tumor tissue at approximately 10(3) CFU/0.1 g by 30 min after infection, and grew in the range of 10(6) CFU/0.1 g to 10(8) CFU/0.1 g by day 4, regardless of their intrarenal growth capacity. In contrast, S. saprophyticus lodged in both tissues to the same degree as S. aureus, but did not grow at all. The time course of the staphylococcal growth was different between tumor tissue and kidney, suggesting differences in the local responses against S. aureus. PMID- 7783689 TI - Evaluation of two assay kits for thermostable direct hemolysin (TDH) as an indicator of TDH-related hemolysin (TRH) produced by Vibrio parahaemolyticus. AB - Reversed passive latex agglutination (RPLA) or enzyme-linked immunosorbent assay kits with beads (Bead-ELISA) are commercially available in Japan to detect the thermostable direct hemolysin (TDH) produced by Vibrio parahaemolyticus isolates. We evaluated whether these kits can be used to assay the pathogenic toxin, TDH related hemolysin (TRH), produced by some so-called Kanagawa phenomenon-negative V. parahaemolyticus strains isolated from patients with diarrhea. Our results showed that the two kits, RPLA and Bead-ELISA, can detect TRH, although they were originally developed for detection of TDH. This may be due to the use of polyclonal anti-TDH antisera that cross react with TRH. Although the sensitivity for TDH detection by RPLA and Bead-ELISA differed tenfold, that for TRH detection was essentially equal. The minimum concentration of TRH required for detection by the two assay kits was about 10 ng/ml. PMID- 7783690 TI - Characterization of an enterotoxin produced by Vibrio cholerae O139. AB - A cholera-like enterotoxin was purified from Vibrio cholerae O139 strain AI-1841 isolated from a diarrheal patient in Bangladesh. Its characteristics were compared with that of cholera toxins (CTs) of classical strain 569B and El Tor strain KT25. Al-1841 produced as much toxin as O1 strains. The toxins were indistinguishable in terms of their migration profiles in conventional polyacrylamide gel disc electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectrofocusing as well as their affinity for hydroxyapatite. The skin permeability factor activity and the fluid accumulation induced in rabbit ileal loops of the toxin of AI-1841 were identical to those of the CTs. Three toxins equally reacted against anti-569B CT antiserum in Western blotting, and their B subunits formed a precipitin line against any anti-B subunit antiserum by double gel immunodiffusion. Anti-569B CTB antibody neutralized the three toxins in their PF activities and enterotoxicities. The amino acid sequence of 1841 toxin B subunit was identical with that of KT25 CTB, corresponding to the DNA sequence of ctxB from El Tor strains of the seventh pandemic. We concluded 1841 toxin was identical to CT of the seventh pandemic El Tor vibrios. PMID- 7783691 TI - Different sensitivity of complement to Salmonella typhimurium accounts for the difference in natural resistance to murine typhoid between A/J and C57BL/6 mice. AB - The difference in natural resistance to Salmonella typhimurium between S. typhimurium-resistant A/J mice and S. typhimurium-susceptible C57BL/6 mice was analyzed. In both strains, the growth of S. typhimurium was controlled in the spleen until 48 hr of infection, while serum C3b levels were increased in A/J mice immediately after infection but not in C57BL/6 mice. Incubation of A/J mouse serum with S. typhimurium or its lipopolysaccharide (LPS) generated sufficient amounts of C3b, but that of C57BL/6 mouse serum with them did not. A/J macrophages had higher intracellular killing activity in vitro than did C57BL/6 cells against S. typhimurium pre-opsonized with each corresponding fresh serum. However, the cells from both mice exhibited a similar level of killing activity against S. typhimurium pre-opsonized with fresh A/J serum or rabbit complement. The resistance of C57BL/6 mice was significantly increased by opsonizing S. typhimurium with fresh A/J serum or rabbit complement before inoculation. The serum level of interferon-gamma (IFN-gamma) in A/J mice was 2.7 times as high as in C57BL/6 mice at 48 hr post-infection. Recombinant murine IFN-gamma enhanced the intracellular killing activity of macrophages from both mice when S. typhimurium was pre-opsonized with fresh A/J serum but not with fresh C57BL/6 serum. These findings suggest that A/J macrophages exhibit maximal killing activity against A/J serum-opsonized S. typhimurium in vivo when the cells are activated with IFN-gamma. Therefore, the rapid and sufficient activation of complement by Salmonella LPS may render A/J mice more resistant against murine typhoid. PMID- 7783692 TI - Varicella vaccine. PMID- 7783693 TI - Losartan for hypertension. PMID- 7783694 TI - Investigation of single and recurrent stone formers. AB - A routine programme for investigation of patients with renal stone disease is presented. The different steps in this process are determined by the stone composition and the patient's previous history of stone formation. Assessment of the supersaturation and the crystallization properties are carried out in urine collected during a 24-hour period in one 16-hour and one 8-hour sample. The programme described in this paper has been formulated with a therapeutic goal in mind, whereby expensive and unnecessary procedures are avoided. PMID- 7783696 TI - Primary hyperoxaluria. AB - Primary hyperoxaluria (PH) is a rare inborn error of amino acid metabolism, now genetically defined, that results in excessive production and urinary excretion of oxalate. It serves as a model of severe nephrolithiasis that requires management of urinary supersaturation to prevent the common outcome of renal failure, which can be the presenting finding: the continued oxalate excess than causes progressive systemic oxalosis (deposition). Routine kidney transplantation almost invariably fails, but a (live donor) protocol that reduces danger of the accumulated load of oxalate can reduce the risk of recurrence. The attractive (and curative) option of combined kidney/liver transplant has considerably greater risk of mortality (in the US), although the European experience is considerably better, often employed earlier in the course. Key to appropriate decisions are early recognition, certain diagnosis, testing for vitamin B6 response, and immediate planning for definitive therapy when renal function is failing. PH provides one example of the absolute need for workup of the metabolic causes of stone disease. PMID- 7783695 TI - Pathogenesis and management of hypercalciuric nephrolithiasis. AB - Hypercalciuria has long been recognized as an important metabolic derangement associated with the formation of calcareous renal stones. Hypercalciuria increases the saturation of the urine with respect to stone-forming salts and reduces inhibitor activity. There is now ample evidence that 'idiopathic hypercalciuria' is a heterogeneous disorder, comprising several entities including absorptive, renal and resorptive forms of hypercalciuria. Absorptive hypercalciuria is the most common variety, and recent studies suggest that in a large subset of these patients, increased intestinal calcium absorption is caused by increased production of calcitriol or greater sensitivity to calcitriol (e.g. upregulation of vitamin D receptors). Reduced spinal bone density found in these patients may relate to increased action of calcitriol on bone or to other factors. Since patients with vitamin D-dependent absorptive hypercalciuria may develop negative calcium balance when placed on diets restricted in calcium, therapy is shifting from severe dietary calcium restriction and sodium cellulose phosphate (calcium-binding resin) to thiazides and orthophosphates, which promote calcium retention. For each form of hypercalciuria, selective therapy should provide the best results. PMID- 7783697 TI - Enteric and mild hyperoxaluria. AB - Enteric hyperoxaluria complicates extensive disease or resection of the small intestine in the presence of an intact colon, and is associated with calcium oxalate nephrolithiasis. In addition to hyperoxaluria these patients have a low urine volume, low urinary ionic strength and hypocitraturia. Many forms of treatment have been recommended, but none has been subjected to a prospective clinical trial. Mild idiopathic hyperoxaluria is reported in 8-50% of idiopathic calcium oxalate stoneformers. Several pathophysiological mechanisms have been proposed, including low dietary calcium and possible oxalate transport defects in the gut and/or the kidney. Mild hyperoxaluria, or a high oxalate:calcium ratio in the urine, may be particularly important risk factors for calcium oxalate stone formation; an approach to the correction of these abnormalities is proposed. PMID- 7783698 TI - Urate and calcium oxalate stones: from repute to rhetoric to reality. AB - A critical appraisal of the evidence commonly cited to support a link between high urate excretion and calcium oxalate (CaOx) urinary calculi is presented. Two theories have been invoked to provide a scientific explanation for urate's apparent promotory effect. The first proposes that urinary urate crystals promote CaOx precipitation by the phenomenon of epitaxy; the second hypothesis is that colloidal particles of urate reduce the inhibitory activity of urinary glycosaminoglycans (GAGs) which normally prevent the crystallization of CaOx. However, to the present, neither has been verified experimentally. More recent research from our group has revealed that at normal physiological pH values dissolved urate directly promotes CaOx precipitation by the classic 'salting-out' effect by enhancing nucleation, growth and aggregation of CaOx crystals. It is therefore suggested that the beneficial effect of allopurinol in reducing CaOx stone recurrences may be attributed to its lowering the urinary output of urate and thereby reducing the probability that CaOx will be salted out of urine, rather than to epitaxy or inactivation of urinary GAGs. PMID- 7783699 TI - Citrate and renal calculi: an update. AB - Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease. PMID- 7783700 TI - Role of nephrocalcin in inhibition of calcium oxalate crystallization and nephrolithiasis. AB - Kidney cells produce at least three proteins that slow the rate of calcium oxalate crystallization. Nephrocalcin (NC), one of the three, is an acidic glycoprotein that contains gamma-carboxyglutamic acid (GLA), and inhibits nucleation, aggregation and growth of calcium oxalate crystals. Nephrocalcin is abnormal in urine of stone-forming patients, in lacking GLA. It acts by absorbing to crystal surfaces. NC is produced by cultured renal proximal tubule cells, and by some lines of renal carcinoma cells, but its regulation is not yet characterized. Its sequence is not known, nor do we known the molecular basis for the abnormal character of NC is stone-forming patients. Compared to Tamm Horsefall protein and uropontin, the two other inhibitors, NC is very potent, and is probably of major importance in protecting kidneys against supersaturations caused by normal water conservation. PMID- 7783701 TI - Uropontin in urinary calcium stone formation. AB - Normal urine is frequently supersaturated with respect to calcium oxalate. Thus, urinary inhibitors of crystallization appear to have an important role in preventing urinary stone formation. Uropontin was isolated by monoclonal antibody immunoaffinity chromatography and has the same N-terminal sequence as osteopontin derived from bone. This urinary form of osteopontin is a potent inhibitor of calcium oxalate monohydrate crystal growth at concentrations (approximately 0.1 microM) that normally prevail in human urine. Interaction with calcium oxalate monohydrate in vivo was shown by analysis of EDTA extracts of calcium stones. Uropontin is an abundant component of calcium oxalate monohydrate stones and present in only trace quantities in calcium oxalate dihydrate and hydroxyapatite stones. However, the precise role of uropontin in the pathogenesis of urinary stone formation is not known and is the subject of ongoing investigations. PMID- 7783702 TI - Tamm-Horsfall glycoprotein and calcium nephrolithiasis. AB - Available data on the effects of Tamm-Horsfall glycoprotein (THP) on calcium oxalate crystallization processes are apparently conflicting. With the main emphasis on calcium oxalate crystal aggregation, this review demonstrates that THP has a dual role as a modifier of crystal aggregation: in solutions with high pH, low ionic strength (IS) and low concentrations of calcium and THP itself, the glycoprotein acts as a powerful inhibitor of calcium oxalate crystal aggregation. Conversely, low pH, high IS and high concentrations of calcium and THP all favor self-aggregation of THP molecules which lowers their inhibitory activity against calcium oxalate crystal aggregation. Some patients with severely recurrent Ca stone disease excrete abnormal THPs which self-aggregate at levels of pH, IS and concentrations of Ca and THP at which normal THPs remain in monomeric form. With high Ca concentrations, such abnormal THPs become strong promoters of crystal aggregation, since conformational changes in crystal-bound THP molecules induce strong viscous binding forces which overcome repulsive electrostatic surface charges. By chelating free Ca ions, citrate reduces self-aggregation of THP molecules and turns promoting THPs into inhibitors of calcium oxalate crystal aggregation. PMID- 7783704 TI - Prevention of recurrent calcium stones: diet versus drugs. AB - Excessive intakes of meat protein, oxalate and potentially sodium, as well as insufficient intakes of vegetables fibers, calcium and fluid all lead to increased urinary crystallization. Renal stone disease, however, does not have to ensue. The underlying condition in a given patient is of paramount importance to allow 'bad eating habits' to lead to nephrolithiasis. Several of these underlying abnormalities have been detected so far from which we recently derived the powder keg and tinderbox theory. Most of the time, the dietary approach to nephrolithiasis allows recurrence of renal stone formation to be prevented. The pharmacological approach should be reserved for refractory cases. PMID- 7783703 TI - Crystal matrix protein--getting blood out of a stone. AB - The short history of crystal matrix protein began in 1991, when it was shown to be the predominant protein present in the organic extract of calcium oxalate crystals precipitated from fresh human urine. Here, we review what has subsequently come to be known about the protein, from its highly specific immunohistochemical distribution in the human nephron, to its finding in kidney stones, to the discovery of its relationship with the human blood coagulation zymogen prothrombin, and, finally, its identification as a urinary form of prothrombin activation fragment 1. A vitamin K-dependent glycopeptide, fragment 1 possesses the so-called GLA domain of its parent molecule; its known properties suggest that it may fulfil a determinant role in calcium oxalate urolithiasis as a potent urinary inhibitor of crystal growth and aggregation. PMID- 7783705 TI - Cystinuria: pathogenesis and treatment. AB - Cystinuria is an inherited disorder of cystine and dibasic amino acids involving renal and intestinal transport mechanisms. Cystine stones are caused by the excessive renal excretion of cystine due to its low solubility in urine. The prevalence of homozygous cystinuria appears to vary in different parts of the world. Cystine stones frequently occur in the second or third decade of life, with an occasional occurrence in infancy and in old age. Urinary cystine excretion exceeding 250 mg/g creatinine is usually diagnostic of homozygous cystinuria. The goal of treatment is to reduce the urinary cystine concentration below its solubility limit (250 mg/l). PMID- 7783706 TI - Uric acid nephrolithiasis. AB - Uric acid is the end-product of purine nucleotide metabolism in man. The renal handling of urate is a complicated process, resulting in a fractional clearance of 8.2-10.3%. The anhydrous form is thermodynamically the most stable uric acid crystal. Uric acid is a weak acid that ionizes with a Pka at pH 5.75. At the normal acidic region, uric acid solubility is strongly increased by urinary pH. The prevalence of uric acid stones varies between countries, reflecting climatic, dietary, and ethnical differences, ranging from 2.1% (in Texas) to 37.7% (in Iran). The risk for uric acid stone formation correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. Hyperuricosuria is the major risk factor, the most common cause being increased purine intake in the diet. Acquired and hereditary diseases accompanied by hyperuricosuria and stone disease include: gout, in strong correlation with the amount of uric acid excreted, myelo- and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia and hemolytic disorders, hemoglobinopathies and thalassemia, the complete or partial deficiency of HGPRT, superactivity of PRPP synthetase, and hereditary renal hypouricemia. A common denominator in patients with idiopathic and gouty stone formers is a low urinary pH. Uric acid nephrolithiasis is indicated in the presence of a radiolucent stone, a persistent undue urine acidity and uric acid crystals in fresh urine samples. A radiolucent stone in combination with normal or acidic pH should raise the possibility of urate stones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783707 TI - [The X-ray fluorescence (XRF) spectrometry of biomaterials used in dentistry. 2]. AB - In this work we analyze the following biomaterial: biomaterials used in this study are: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxiapatite. The quantitative XRF analysis was performed by a Philips PW 1480 with Rh tube. This research, besides underlining the possibility of applying the XRF method to the analysis of biomaterials. This study, shows the facility and the rapidity in the preparation of samples and standards in the form of tablets to undergo the analysis: furthermore the study shows the possibility of verify the analysis on the same sample in the future, because the tablet if well conserved, does not deteriorate. We can also verify a good analytic accuracy both for the principal elements (Ca, P) and for trace elements. The analyses show a moderate variability in the Ca/P ratio in the hydroxylapatites, and a greater variability in the secondary and trace elements. PMID- 7783708 TI - [X-ray powder diffraction (XRD) in the study of biomaterials used in dentistry. 3]. AB - This study considers X-ray power diffraction (XRD) applied to the study of mineral-based biomaterials used in odontostomatology. By means of this method the following materials were analysed: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable fine Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-oss, Biostite, Osprovit, Merck Hydroxyapatite. These analysis allow the identification of the crystalline phases, the study of the crystallinity and the crystal chemistry of the samples prepared as powder mixtures. This method permits the determination of the physical chemical and crystalline characteristics of these mineral based biomaterials formed by powders or transformable in powders. All of this information is indispensable for the evaluation of the functional biocompatibility of a biomaterial when its reaction in a biological environment is already known. This method has a great number of advantages against the traditional methods, marking with solid phases, it does not destroy the sample, it does not modify the physical or chemical characteristics and gives more information. PMID- 7783709 TI - [The characteristics and properties of calcium phosphates in biomaterial formulations used in dentistry. 1]. AB - In this work we present the features and the properties of natural and synthetic apatites, which we use in an experimental study of various commercial products composed by calcium phosphate. After having considered the general concepts of biomaterials and biocompatibility, we describe non biological tests used for the characterization of these products. Biomaterials used in this study are: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2 Osprogel, Bio-oss, Biostite, Osprovit, Merck Hydroxiapatite. Tests used are: X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric and thermodifferential analysis (TG, DTG, DTA), scanner-ing electron microscopy (SEM) morphological analysis. Last but not least, we underline the particular features of these tests whose interpretation allows a more precise definition of the bioactivity of a biocompatible material. PMID- 7783710 TI - [The characterization by Fourier-transform infrared vibration spectroscopy of mineral-based biomaterials commonly used in dentistry. 4]. AB - In this study the following biomaterials were analysed by means of Fourier transform infrared vibrational spectroscopy (FTIR); they are: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable fine Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2 Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxyapatite. The analysis was performed with a Jasco 5300-FTIR. At 64 readings for spectrum with a 2 cm-1 resolution. By means of this method it has been possible to perform a structural study at a molecular level of the commercial products mentioned before. The analysis showed which of the samples examined had lost the apatite OH- group during production. It also allowed the identification of some of the hydroxyapatites examined as carbonate apatites. Finally, it allowed the identification and quantification of the organic substances in the examined products. PMID- 7783711 TI - [The thermal analysis of mineral-based biomaterials used in dentistry. 5]. AB - In this study the following commercial products were thermo-analysed (TG, DTG, DTA): reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxiapatite. The apparatus utilized was a Setaram TAG 24, in a symmetrical set up, which gave the TG, DTG and DTA analysis simultaneously. The analysis of all the materials were performed in correct operative conditions. The thermo analyses gave useful information about the thermal stability of the samples. The TG analysis gave the data relative to the percentage of weight loss due to the volatile substances in the samples (H2Oass C, OH-, CO2). The DTG graph made it possible to establish the presence of carbonate apatite and/or hydroxyapatite or the absence of both the substances. Finally, DTA and DTG analyses allowed show the presence of various organic substances. These data were very useful to characterize the examined materials and confirmed the extreme importance and sensibility of this method. PMID- 7783712 TI - [Scanning electron microscopy (SEM) and microanalysis (EDS) applied to the study of biomaterials for dental use. 6]. AB - The study considers the use of scanning electron microscopy (SEM) and EDS microanalysis applied to the study of numerous mineral-based biomaterials of common use in odontostomatology. The products studied are the following: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non rabsorbable fine Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Ospro vit, Merck Hydroxyapatite. By means of SEM it was possible to study the morphology and the microchemistry of the various biomaterials so as to have information about their physical and chemical characteristics, such as the crystalline form, the crystalline aggregations, the space dimensional distribution of the pores and check the possibilities of composition variability. All of these factors are fundamental to evaluate the functional biocompatibility of a biomaterial, once that its performance in a biological environment is known. PMID- 7783713 TI - [The specific characteristics determined by nonbiological tests of mineral-based biomaterials used in dentistry. 7]. AB - In this work we relate about the results coming from crystallographic, physical and mineral tests taken on following biomaterials used in odontostomatology: reabsorbable Dac Blu, non reabsorbable Dac Blu, not reabsorbable atomized Dac Blu, not reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxiapatite. The data were obtained using the following tests: XRF, XRD, FTIR, TG, DTG, DTA, SEM. The results, although taken on few samples, showed that these biomaterials present a variability in some features, which can define the structural functionality. PMID- 7783714 TI - Laser surgery for retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is a common eye disorder occurring in preterm infants. Formally known as retrolental fibroplasia, ROP is defined as a vasoproliferative disorder that occurs in the developing retina of premature infants' eyes. Until recently, cryotherapy was the recommended treatment for infants diagnosed with advancing ROP. Now laser surgery is being used as an alternative treatment. This article reviews the pathophysiology, etiology, and classification of ROP, considers the pros and cons of laser surgery versus cryotherapy, and outlines the experience with laser surgery in our NICU. PMID- 7783715 TI - Adhesive tape vs pectin-based barrier use in preterm infants. AB - This controlled trial studied 20 premature infants, 28-33 weeks of gestational age, over 21 days. It compared the gross skin condition on the side of the face where tape was applied directly to the skin to anchor a nasogastric tube to the other side, where the tape was applied over a pectin-based barrier. Ninety-four percent of the infants had no gross signs of skin breakdown on the side under the barrier for as long as 21 days. In contrast, 80 percent of the same infants had gross signs of skin breakdown within five days on the side of the face where the tape was applied directly to the skin. The results indicate that a pectin-based barrier should be applied when tape must be used to anchor equipment in premature infants. PMID- 7783716 TI - Differential diagnosis: a case study. AB - Health care professionals who care for neonates must be able to recognize early signs/symptoms that suggest acute illness. Such early recognition and appropriate management may improve outcome. This article presents a case study and permits the reader to evaluate data and make decisions about diagnoses and treatment. Current research-based approaches to management are also discussed. PMID- 7783717 TI - Predictors of postnatal head molding in very low birth weight infants. AB - This study examined potential predictors of postnatal head molding in very low birth weight (VLBW) infants. Occipital-frontal circumference (OFC) and anterior posterior (AP) and biparietal (BP) diameter measurements were obtained on 144 premature infants with birth weights of less than 1,500 gm. Measurements were obtained at four days of age (baseline) and weekly until discharge. Increasing gestational age, higher birth weight, and delivery by cesarean section predicted larger OFC at three weeks of life. Only baseline AP:BP measurements significantly predicted AP:BP measurements at week 3 and 5. Within-group t-tests indicated that the severity of head molding (as indicated by AP:BP ratio) increased throughout the first six weeks of life. Results indicate that postnatal head molding can be reliably predicted and that neonates with higher AP:BP ratios at birth are at greater risk for continued narrow, elongated head shape. PMID- 7783718 TI - Integrating research into clinical practice. PMID- 7783719 TI - Vancomycin levels: to monitor or not to monitor. PMID- 7783720 TI - The effect of feeding method on the oxygen saturation of the premature infant. PMID- 7783721 TI - Get the most out of a literature search using a computerized system. PMID- 7783723 TI - Educating secondary caregivers. PMID- 7783722 TI - Clinical practice and research. PMID- 7783724 TI - A laying off of hands. PMID- 7783725 TI - Research utilization: pharmacologic management of neonatal pain. AB - Opioids, particularly morphine sulfate and fentanyl, continue to be the most commonly used agents for analgesia. Morphine provides greater sedation, and there is less of a problem with rigidity of the chest wall than with fentanyl. Morphine also has a higher level of tolerance than does fentanyl. Table 2 provides considerations for administration of morphine and fentanyl. Sedation for the relief of pain without analgesia is not acceptable. Sedation and analgesia together may be in the baby's best interest. Before any plan of care is implemented, the baby should be evaluated for need based on the amount of current respiratory support versus spontaneous respiration. There is evidence in the research literature that narcotic administration can be safely carried out in the preterm when using intravenous caffeine simultaneously to offset the risk of apnea. Others state that there really is no safe therapeutic window for narcotic administration in the preterm infant, yet the benefits outweigh the respiratory depressant effect. The complication of respiratory depression can be readily dealt with through the administration of neonatal Narcan via the intramuscular, intratracheal, or intravenous routes. PMID- 7783726 TI - Methadone maintenance and breast feeding continued.... PMID- 7783727 TI - Reflections for Jason. PMID- 7783728 TI - Renal physiology Part 1: Structure and function. AB - To assess, plan, and implement care of the critically ill neonate, the nurse must have a thorough understanding of renal embryology and physiology. This articles focuses on the developmental and anatomical structure of the kidney and the general physiological activities of the renal components. Renal embryological development begins during the 1st week of gestation and continues until around the 36th week of gestation. Functional capacity, although not mature, begins around the 6th week of gestation. Infants born premature have underdeveloped structures and decreased renal function. Comprehending renal anatomy and physiology requires a complete understanding of a single nephron, the functional unit of the kidney. Each nephron consists of a glomerulus, Bowman's capsule, and tubules, which work together to maintain ion balance for cellular function and elimination of unwanted substances from the plasma. Renal blood flow, controlled by either autoregulation or hormonal control, must remain both rapid and constant for glomerular filtration to occur. Alterations in any of these components of renal anatomy and physiology will alter the condition of the neonate. Renal evaluations are done based on output, urine chemistries, and serum chemistries. These evaluations lead to a diagnosis on which the nurse can base her plan of care. PMID- 7783729 TI - Heat--related illnesses and deaths-United States, 1994-1995. AB - Although heat-related illness and death are readily preventable, exposure to extreme temperatures causes at least 240 deaths during years with no heat wave. A heat wave is defined by the National Weather Service as > or = 3 consecutive days of temperatures > or = 90.0 F (> or = 32.2 C). In 1980, 1983, and 1988 (recent years with prolonged heat waves), 1700, 556, and 454 deaths, respectively, were attributed to heat. This report describes four instances of heat-related illness and death that occurred in the United States during 1994 and 1995 and summarizes risk factors for heat-related illness and death. PMID- 7783730 TI - Update: outbreak of Ebola viral hemorrhagic fever--Zaire, 1995. AB - As of June 25, public health authorities have identified 296 persons with viral hemorrhagic fever (VHF) attributable to documented or suspected Ebola virus infection in an outbreak in the city of Kikwit and the surrounding Bandundu region of Zaire (1,2); 79% of the cases have been fatal, and 90 (32%) of 283 cases in persons for whom occupation was known occurred in health-care workers. This report summarizes characteristics of persons with VHF from an initial description of cases and preliminary findings of an assessment of risk factors for transmission. PMID- 7783731 TI - Update: management of patients with suspected viral hemorrhagic fever--United States. AB - In 1988, CDC published guidelines for managing patients with suspected viral hemorrhagic fever (VHF) (1). Pending a comprehensive review of the 1988 guidelines, this notice provides interim recommendations that update the 1988 guidelines for healthcare settings in the United States. This update applies to four viruses that cause syndromes of VHF: Lassa, Marburg, Ebola, and Congo Crimean hemorrhagic fever viruses; although the risk and/or mode of nosocomial transmission differs for each of these viruses, the limited data do not permit clear distinctions. PMID- 7783733 TI - [CG-methylation and mutagenesis of human mitochondrial DNA]. AB - It is demonstrated that human mitochondrial DNA (mtDNA) exhibits the chain asymmetry of TG and CA dinucleotide frequencies presumably due to replicative and postreplicative methylation of CG sites of mtDNA and specific mitochondrial genome replication. The analysis of population data on human mtDNA variability has revealed two mutation flows: one intense G-->A and C-->T and less intense A- >G, T-->C and C-->G flows; the letter results in formation of G,C-enriched mtDNA palindromic structures and CG dinucleotides. The interaction of these two mutation flows through the system of DNA methylation/deamination enables to consider the above mentioned processes as a mechanism of DNA evolution maintaining certain level of mtDNA diversity in human populations. PMID- 7783732 TI - [Results of work on the project "Instruments, reagents, probes" of the state scientific-technical program "Human genome" (1989-1994)]. AB - This report reviews the activities of the "Reagents, Devices, Probes" branch of the Russian State "Human Genome" Project for six-year period (1989-1994). Data on pilot and commercial production of reagents and equipment for human genome studies along with information on the project costs and awarded grants are presented. PMID- 7783734 TI - [Determination and analysis of the primary structure of a genomic sequence adjacent to the 3'-end of the human tissue plasminogen activator gene]. AB - Primary structure was determined for the recently cloned f1/BglII-fragment [19] containing 2102 b.p. of the human tissue plasminogen activator (tPA) gene 3' end and adjacent DNA region. Computer analysis has revealed an Alu-repeat 820 b.p. downstream the tPA gene; the sequence proved to have a considerable homology (86 88%) with the Alus from the 3'-untranslated regions (3'UTRs) of cytochrome P-450, lysozyme and p53 protein human mRNAs. The same homology was estimated for this Alu in reversed orientation and Alus from the 3'UTRs of some other human mRNAs. In contrast, the homology between this 3' end tPA gene flanking Alu-repeat and other Alus dispersed throughout the gene introns either direct or reversed, was less than 70%. The polyadenylation signal AATAAA downstream the Alu and two nearby signals CACAG and GTGTT resembling consensus sequences CACAG and YGTGTTYY, respectively, were also detected. The two latter motifs located close to the 3' ends in most mammalian genes are likely to regulate mature mRNA formation. The comparison of the sequenced spaser flank adjacent to the tPA gene with short homologous sequence from the same genomic region primary structure reported previously has revealed discrepancies (substitutions, deletions or insertions) in 21 nucleotide positions. The nucleotide sequence of E. coli uvrB gene fragment (980 b.p.) is also reported. This E. coli gene fragment was cloned accidentally within the f1/BglII-fragment being an artifact of the host-vector system used. PMID- 7783735 TI - [The critical significance of a conserved single-stranded interdomain linker in the 5'-untranslated region of poliovirus RNA]. AB - Translation of polioviral RNA is initiated by interaction of a small ribosomal subunit with internal segments of the 5'-untranslated region (5'UTR). Several mutations were constructed within 5'UTR segment 425-449. All of them (including a single C444-->U replacement) inhibited in vitro translation, which decreased about 10-fold. Two mutant constructs, pPV12-05 (C444-->U) and pPV12K (containing also an AAUU insert between positions 441 and 442) produced plaques on monolayers of susceptible cells. All the viruses isolated from these plaques exhibited a reversion at position 444; the template activities of the revertant RNAs were restored completely or significantly. The results show the importance of the relevant 5'UTR segment for the initiation of polioviral RNA translation. PMID- 7783736 TI - [The mutagenic activity of N4-(4-aminobutoxy)-2'-deoxycytidine-5'-triphosphate]. AB - We have shown that deoxycytidine-5'-triphosphate modified by O-(4 aminobutyl)hydroxylamine in the pyrimidine ring, is effectively incorporated into DNA synthesizing in vitro, replacing deoxythymidine-5'-triphosphate or deoxycytidine-5'-triphosphate and inducing A-->G and G-->A transitions, respectively. UV spectroscopy and NMR spectroscopy have shown that the modified cytidine-5'-triphosphate is identical to N4-(4-aminobutoxy)-2'-deoxycytidine-5' triphosphate. When the modified deoxycytidine-5'-triphosphate was inserted into DNA in vitro by DNA polymerase I of E. coli Klenow fragment, retardation sites correlating with poly-A sites (when the modified triphosphate replaced deoxythymidine-5'-triphosphate) or with poly-G sites (when it replaced deoxycytidine-5'-triphosphate) were revealed. Our data show high mutagenic effect of the modified deoxycytidine-5'-triphosphate inserted into DNA, allowing us to recommend this compound for localized static mutagenesis. PMID- 7783737 TI - [Cloning and analysis of the nucleotide sequence of the segment in the Mycoplasma gallisepticum genome containing the gene for the ATP-binding subunit of DNA topoisomerase type II (topIIB)]. AB - M. gallisepticum genome fragment carrying complete coding sequence for ATP binding subunit of topoisomerase II (topIIB), partial coding sequence for N terminal part of A-subunit of topoisomerase II and region upstream of topIIB gene (open reading frame encoding 99 amino acids) was sequenced. The nucleotide sequence of topIIB has significant homology with previously reported gyrase genes and parE gene of E. coli. No protein sequence significantly similar to the open reading frame upstream from the gene topIIB was found in GeneBank data. PMID- 7783739 TI - [Study of the interaction of a DNA molecule with coordination compounds of divalent platinum. I. Effect of cis-diaminodichloroplatinum on molecular parameters of DNA in solution]. AB - DNA interaction with cis-diaminodichloroplatinum (cis-DDP in solutions of different ionic strength was studied by flow birefringence, viscometry, circular dichroism. Though cis-DDP is not an electrolyte, electrostatic interactions are important for binding of cis-DDP with DNA probably for transporting cis-DDP to a macromolecule. The charges aqua-complex is formed by cis-DDP. The complexation being dependent on the platinum/DNA ratio in solution. Along with the increase of platinum concentration, it forms first the complexes with phosphate groups, then with bases without destruction of the DNA secondary structure. The next type of complex formation is accompanied by the local destruction of the hydrogen bonds and stacking interactions. And when the Pt/DNA ratio grows high enough, DNA is denatured. It is suggested that the stability of the complex is provided by nitrogen groups of the bases incorporated in the platinum first coordination sphere. The phosphate DNA groups play the role of counterions in the external coordination sphere. PMID- 7783740 TI - [A synthetic zinc chelating peptide competes for DNA binding sites with antibiotics, adsorbed in a minor DNA groove]. AB - Effects of sibiromicyn, distamicyn A and its analogs on binding to DNA and to poly(dA).poly(dT) are reported for a 23-amino acid synthetic zinc-binding peptide, a part of the DNA-binding domain of the transcriptional activator GAL-4. Circular dichroism and fluorometry have shown that the synthetic peptide and two distamicyn A analogs compete for binding sites on DNA and on poly(dA).poly(dT). Antibiotic sibiromycin which forms a covalent bond with a guanine 2-amino group in the minor DNA groove can displace the peptide from a 19 bp self-complementary oligonucleotide serving as a specific target site for Gal-4 protein. The peptide is shown to bind to a glucosylated phage T2 DNA, but its affinity to T2 DNA is weaker than to calf thymus DNA under the same conditions. A method to estimate binding constant and size of the binding site for the synthetic peptide and poly(dA).poly(dT) is proposed based on the binding isotherms of distamycin analogs in the absence and in the presence of the peptide. Using isotherms of binding to poly(dA).poly(dT) for two distamycin analogs with binding constants differing 60-fold, the binding constant of the peptide in the presence of 0.1 M NaCl is estimated as 1.4.10(7)-1.8.10(7) M-1. PMID- 7783741 TI - [The possible role of rare tautomers of DNA bases in mutagenesis: study of the effect of hydration on tautomeric equilibrium by the Monte-Carlo method]. AB - Monte Carlo simulation of hydration of keto and enol tautomers of 9-methylguanine (G) and 1-methyluracil (U) has been performed in relation to a possible role of tautomer transitions of DNA bases in mutagenesis. The comparison of the simulation results with published experimental data and results of quantum mechanical computations leads us to conclusion about difference in the origins of keto-form prevalence in water solutions of G and U. Such a reason for uracil (thymine) is a greater intrinsic stability of keto tautomer while the more preferable hydration of keto form of G is the reason of its predominance. As a consequence, during biosynthesis less hydrophylic environment (as compared to water solution) can be a reason for guanine transition into enol form and can result in mispair formation. Such a mutation mechanism is of a minor probability through thymine (uracil) tautomerization. PMID- 7783738 TI - [Study of conformation transitions in proteins by tryptophan fluorescence and phosphorescence at low temperatures]. AB - The well-known conformational changes in proteins containing a single tryptophan residue, such as pH-induced N-->F transition in human serum albumin, pH-induced acidic transition in cod parvalbumin, and KCl-induced tetramerization of bee venom melittin were monitored by changes in low temperature phosphorescence and fluorescence spectra suggesting two independent series of normal components. Parameters of low temperature tryptophan luminescence were sensitive to chromophore environment. A correlation of changes of some spectral parameters with accessibility of tryptophan to water was revealed, however, spectral changes mainly depend on specific interactions of the chromophore with its environment. PMID- 7783742 TI - [The mechanism of tautomeric transitions of nucleic acid bases with limited access to water molecules]. AB - Pathways of tautomeric transformations of nucleic acid bases have been considered in the conditions when only few separate water molecules can interact with the bases. Field ionization mass-spectrometric study has demonstrated that substitution of one of the labile hydrogen atoms for deuterium takes place when thymine (or 1-methylthymine) interacts with heavy water in vacuo. This observation was explained by a supposition that a transient water-thymine complex is formed and then tautomeric transition of the base occurs via double proton transfer along hydrogen bonds. Calculations of the interaction energy between base and water molecules allowed us to suggest the structure of such a complex in which water molecule lays in the plane of the base. Formation of such complexes during biosynthesis of nucleic acids can give rise to point errors, probability of their appearance being dependent on the structure and properties of a macromolecular DNA-enzyme-nucleotide complex. PMID- 7783743 TI - [Production of biologically active recombinant ricin B-chain]. AB - Escherichia coli cells transformed with plasmids containing ricin B-chain coding sequences are shown to express this heterologous protein in inclusion bodies. After denaturation and renaturation of the product in the presence of glutathione and lactose, the recombinant ricin B-chain is soluble, biologically active and stable. Cytotoxicity of heterodimer containing this protein and ricin A-chain is found to be only ten times lower, than that of native ricin. Recombinant B-chain alone was nontoxic to cells (ID50 > 10(-6) M). Our data suggest that ricin B chain oligosaccharides are essential for stability preserving protein from proteolytic degradation in cells. PMID- 7783745 TI - [Analysis of stationary kinetics of translation elongation within the framework stereospecific stabilization hypothesis of codon- anticodon complexes in a ribosome. I. Kinetic schemes of factorless elongation]. AB - Dependences of steady-state rates of polypeptide elongation on concentrations of substrate (aminoacyl-tRNA) and product (deacylated tRNA) in the absence of elongation factors and GTP are theoretically analyzed in context of stereospecific stabilization of the codon-anticodon complexes at a ribosome. General kinetic scheme and different ribosome isomerization stages are examined. The effect of isomerization stage allows to identify reaction stage experimentally. Regulation of the direct reaction by product and regulation of the reverse reaction by substrate are possible. Under certain conditions elongation system may show kinetic cooperativity. PMID- 7783744 TI - [Reactions of 5'-H-phosphonates, 5'-F-phosphates, and 5'-phosphates of modified thymidines in human blood plasma]. AB - Mechanisms and rates of hydrolytic dephosphorylation of 5'-hydrogen phosphonates, 5'-fluorophosphates, and 5'-phosphates of 3'-azido-3'-deoxythymidine, 3'-fluoro 3'-deoxythymidine, and thymidine in human blood serum were investigated. 5' Hydrogen phosphonates of 3'-substituted thymidines are dephosphorylated 50-100 times slower than the corresponding 5'-phosphates. 5'-fluorophosphates of 3' substituted thymidines are dephosphorylated 2 times slower than corresponding 5' phosphates; first, substituted thymidine 5'-phosphates are formed, which are later dephosphorylated into substituted thymidines. These data illustrate probable molecular mechanisms of anti-HIV action of such nucleotides. 5'-hydrogen phosphonates of thymidines can serve as depot forms of corresponding thymidines, but other metabolic pathways are not excluded. Thymidine 5'-fluorophosphates can serve as depot-forms of both thymidines and their phosphates. Their fate in cells depends probably on their diffusion and on the activities of dephosphorylating and phosphorylating enzymes. PMID- 7783746 TI - [Analysis of stationary kinetics of translation elongation within the framework of the stereospecific stabilization hypothesis of codon- anticodon complexes in a ribosome. II. Kinetic schemes in the presence of protein elongation factors and GTP]. AB - Kinetics of the factor-dependent polypeptide elongation is theoretically studied in context of stereospecific stabilization of the codon-anticodon complexes at a ribosome. Kinetic schemes for the different ribosome isomerization stages are examined. The dependence of steady-state elongation rate on elongation factor concentration for each of the schemes is unique, allowing to identify isomerization stages experimentally. PMID- 7783747 TI - [Formation of 8-hydroxyguanine upon damage of guanine nucleotides by gamma radiation]. AB - Formation of 8-hydroxyguanine derivatives caused by the exposure of aqueous solutions of guanine nucleosides and nucleotides (Guo, dGuo, GMP, dGMP, GDP, and GTP) to gamma-radiation was studied by differential UV-spectroscopy. 8 hydroxyguanine had linear dose-yield relationship with G-value (radiation chemical yield) of 0.2-0.4 molecules per 100 eV. Data on irradiation of D2O solutions of nucleotides show that the mechanism of gamma-radiation-induced formation of 8-hydroxyguanine is probably different from that of heat-induced one. Levels of intracellular guanine nucleotide pool damage caused by natural background radiation and induced by heat were compared for different temperatures. Level of DNA precursor pool damage by natural background radiation at 37 degrees C is insignificant and comprises approximately 0.2% of the heat induced damage but rises sharply as the temperature decreases. The possible biological consequences of gamma-radiation-induced damage of guanine and deoxyguanine nucleotide cell pools are discussed. PMID- 7783748 TI - [Group-selective immunoanalysis]. AB - The new solid-phase immunoassay technique has been applied for antidigoxin monoclonal antibodies (Mabs) detection. At the first assay step, antidigoxin Mabs (IgG1, Kaff = 9.2 x 10(9) M-1) bound with specially prepared immunosorbent: microtiter plates with adsorbed digoxin-human serum albumin conjugate, in which free amino groups were blocked by glutaraldehyde (the microtiter plates with immobilized conjugate were treated for 3h by 2.5% glutaraldehyde at 45 degrees C, this had no significant effect on the immunological properties of immunosorbents). After antigen-antibody reaction and solid phase separation, free amino groups were located only at the antidigoxin Mabs bound to GSI immunosorbent. At the second assay step, N-hydroxysuccinimide-biotin ester solution was added to bind with the free amino groups. After separation at the third assay step, biotin labels were detected by the streptavidin-peroxidase conjugate. The method does not require second labeled antibodies and may be used for anti-hapten screening. PMID- 7783749 TI - Single peptide and anti-idiotype based immunizations can broaden the antibody response against the variable V3 domain of HIV-1 in mice. AB - The third variable (V3) domain of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 is a major target of neutralizing antibodies in infected persons and in experimental immunized animals. Given the high degree of sequence variability of V3, the humoral response toward this region is very type-specific. In the present study, we evaluated the potential of a single peptide and an anti-idiotypic antibody to broaden the anti-V3 antibody specificity in BALB/c mice. We show that a synthetic peptide derived from the V3 determinant of HIV-1 MN isolate (V3MN), when used as an immunogen, was able to induce an antibody response to multiple (up to six) HIV-1 strains. The extent of this cross-reactivity, which tended to enlarge as the injections increased, appeared to be inversely correlated with the binding affinity to V3MN peptide. These data thus present evidence that, despite its great sequence heterogeneity, the V3 loop encompasses conserved amino-acid positions and/or stretches which may be less immunogenic than their variable counterparts. We additionally demonstrate that a rabbit anti-idiotype (Ab2), recognizing a binding site related idiotype on a V3-specific mouse monoclonal antibody (Ab1), could mount a broadened humoral response (Ab3) in mice. Unlike nominal antibody Ab1 which strictly reacted with the European HIV-1 LAI isolate, elicited Ab3 recognized the two divergent HIV-1 strains SF2 and 1286, originating respectively from North America and Central Africa, in addition to LAI. The reasons accounting for this Ab2-induced enlargement of the V3 antibody response are discussed. Our findings suggest that single peptide and anti-idiotype based immunizations may provide viable approaches to overcome, at least in part, HIV epitope variability. PMID- 7783750 TI - Evidence that the hinge region plays a role in maintaining serum levels of the murine IgG1 molecule. AB - The site of the murine IgG1 molecule that regulates catabolism has recently been shown to encompass amino acids that are located at the CH2-CH3 domain interface. The CH2 and CH3 domains are connected to each other by a relatively flexible "mini-hinge" region, and flexibility in this region could clearly affect the orientation of the domains with respect to each other. The internal movement of the CH2 domain depends on the absence/presence of the hinge disulphide. The increased mobility of the CH2 domain relative to the CH3 domain in a hinge less IgG or Fc fragment may result in a conformational change at the CH2-CH3 domain interface and alter the accessibility of the residues that are involved in catabolism control. To investigate this possibility, four Fc fragments which differ in the presence/absence of hinge disulphides and hinge sequences have been analysed in both in vivo pharmacokinetic studies and in vitro by limited proteolysis with pepsin. The data show that the presence of hinge disulphide(s) in the Fc fragment results in a longer intravascular half life but a higher susceptibility to pepsin attack. This, taken together with the knowledge that pepsin cleaves close to the CH2-CH3 domain interface, suggests that the longer half life of disulphide linked Fc fragments relative to unlinked fragments may be due to conformational differences in this region of the IgG molecule, and these conformational changes may affect the accessibility of the catabolic site for binding to putative protective Fc receptors. PMID- 7783751 TI - Immunoglobulin isotype switching in xid mice. AB - Mice with the x-linked immunodeficiency mutation (xid) are unresponsive to polysaccharide antigens, lack a subset of B cells, and have low serum IgM (2-20% of normal) and IgG3 (3% of normal). Because of the disproportionate reduction of IgG3, the ability of B cells from xid mice to switch to gamma 3 was examined. Switching was indirectly measured by comparing IgG3 production and C gamma 3 mRNA steady state levels of purified B cells activated to switch to IgG3 by LPS in bulk culture. Direct measurement of switching was achieved by enumerating on a percentage basis switched cells in a filter disk culture assay and by FACS analysis. In both bulk culture and the filter disk assay, switching to gamma 3 was equivalent between xid and non-xid B cells. PMID- 7783752 TI - Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice. AB - The nature of the stimuli driving autoantibody production in systemic lupus erythematosus (SLE) is unclear, but cytokines are believed to play an important role. Since cytokines primarily appear to act locally at the tissue level, we analysed mRNA expression of several cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN gamma, TNF alpha, TNF beta and TGF beta 1) in the lymph nodes of lupus-prone mice, in models of early onset disease. We constructed a multispecific competitor fragment that allowed quantification of these cytokine transcripts by competitive PCR assay. The results reveal considerable overexpression of IL-1 beta, IL-10 and IFN gamma transcripts in SLE-prone MRL lpr/lpr (MRL/l) and BXSB male (BXSBm) mice, but with some strain differences. IFN gamma was most markedly augmented in MRL/l mice (in some cases over 100-fold greater than control mice), IL-1 beta was most severely overexpressed in BXSBm mice while IL-10 was equally increased in both strains. In addition, TGF beta 1 expression was moderately elevated in the lymph nodes of BXSBm (but not MRL/l) mice. We found no abnormality in the expression of the other cytokines. Cytokine transcript levels were only slightly altered at 4 weeks of age, but were elevated from 10 to 22 weeks of age. The latter phase corresponds to a period where lupus like disease escalates, resulting in frequent mortality. Interestingly, our results do not reveal a clear Th1 or Th2 cytokine expression pattern in these lupus-prone mice. IL-1 beta, IFN gamma and IL-10 are pleiotropic cytokines with pro-inflammatory and B-cell stimulatory effects. These results point to certain cytokines as potential targets for immunotherapy in lupus. PMID- 7783753 TI - Recombinant allergen Lol p II: expression, purification and characterization. AB - Pollen from perennial rye grass (Lolium perenne) is a major cause of type I allergies worldwide. It contains complex mixtures of proteins, among which Lol p II is a major allergen. Previously, we have reported the cloning and sequencing of Lol p II and its expression in fusion with the heavy chain of human ferritin as carrier polypeptide (Sidoli et al., 1993, J. biol. Chem. 268, 21819-21825). Here, we describe the expression, purification and characterization of a recombinant Lol p II overproduced as a non-fusion protein in the periplasm of E. coli. The recombinant allergen was expressed in high yields and was easily purified in milligram amounts. It competed with the natural Lol p II for binding to specific IgE, and it induced allergic responses in skin prick tests, indicating to be immunologically analogous to the natural protein. Biochemical analyses indicate that recombinant Lol p II is a highly stable and soluble monomeric molecule which behaves like a small globular protein. PMID- 7783754 TI - Effect of VH and VL consensus sequence-specific primers on the binding and neutralizing potential of a single-chain FV directed towards HuIFN-gamma. AB - We have previously reported on the cloning and bacterial expression of a biologically active scFv antibody fragment (scFv-D9D10) derived from the mouse anti-human interferon-gamma (HuIFN-gamma) antibody, D9D10. Since the variable (V) regions were isolated by means of VH and VL consensus sequence-specific PCR primers and cloned in an expression vector relying on primer-incorporated restriction sites, some amino acids (aa) at the N- and C-terminal ends of the cloned V domains were expected to differ from the corresponding ones in the natural D9D10 antibody. Therefore, the naturally occurring sequences of both V domains were isolated by means of traditional cDNA synthesis procedures. In comparison with scFv-D9D10, the "natural" V sequences differed in three aa in VH and three in VL. The V domains of scFv-D9D10 were adapted to their natural sequence by means of PCR-directed mutagenesis to yield scFv-D9D10N. Comparison of the binding and neutralizing potentials of both antibody fragments did not reveal differences in either of both activities. In addition, their affinities for HuIFN gamma were found to be equal. These results show that murine VH and VL consensus specific primers can yield antibody fragments having functional properties equivalent to those of the natural scFv. Information on the impact of the use of V-specific primers on kinetics of interaction between the recombinant antibody and the corresponding antigen is important for the development of most engineered antibodies or their fragments. PMID- 7783755 TI - Isolation and characterization of a new basic antigen from short ragweed pollen (Ambrosia artemisiifolia). AB - A new basic antigen with a molecular weight of 36.5 kDa and a pI of 8.65 was purified from short ragweed pollen using ammonium sulfate precipitation, Q sepharose chromatography and S-sepharose chromatography. The purified protein, herein referred to as Ambrosia artemisiifolia basic antigen (AaBA), migrated as a single band in SDS-polyacrylamide gel electrophoresis and isoelectric focusing, and as a single peak on reverse phase HPLC. AaBA reacted with sera from humans allergic to ragweed pollen including pooled NIH serum. AaBA and two major acidic allergens, Amb a I (antigen E) and Amb a II (antigen K), displayed immunological cross-reactivity inasmuch as they competed significantly with each other in a competition ELISA. This suggests that at least some major epitopes in all three antigens are similar; however, other possibilities like adjacent location of different epitopes cannot be ruled out at this time. Molecular weight, amino acid composition and sequence data suggest that AaBA is very similar to Amb a II whereas it is significantly different from other basic antigens purified from ragweed pollen. PMID- 7783756 TI - Characterization of class I MHC folding intermediates and their disparate interactions with peptide and beta 2-microglobulin. AB - Newly synthesized class I heavy chains achieve domain structure using disulfide bonds, assemble with beta-2 microglobulin (beta 2m), and bind peptide ligand to complete the trimeric complex. Although each of these initial events is thought to be critical for class I folding, their sequential order and effect on class I structure are unknown. Using mAb specific for distinct conformations of H-2Ld and Lq, we have defined folding intermediates of class I molecules. We show here that non-peptide-associated forms of Ld or Lq, detected by mAb 64-3-7 and designated L alt, lack numerous conformational epitopes surrounding their ligand binding sites. These results support the notion that L alt molecules have an open conformation. Interestingly, a significant proportion of L alt molecules were detected in association with beta 2m and these L alt/beta 2m heterodimers were preferentially folded by peptide in cell lysates. These findings indicate that class I heavy chain/beta 2m association can precede ligand binding and that peptide is probably the limiting factor for completion of the Ld/beta 2m/peptide trimeric complex in vivo. The characteristics of L alt molecules were investigated further by ascertaining the disulfide bond status of these molecules and their association with beta 2m and peptide. Treatment of cells with dithiothreitol (DTT), a membrane-permeable reducing agent, demonstrated that L alt molecules constitute a heterogeneous population including reduced, partially reduced and native class I molecules. Furthermore, partially reduced Ld alt molecules, in a cell line expressing a mutant Ld molecule lacking the alpha 2 domain disulfide bond, accumulated intracellularly, were not beta 2m-associated and displayed marginal peptide-induced folding in vitro. In accordance with this latter finding, peptide was found to preferentially convert fully disulfide bonded forms of Ld alt to conformed Ld. Thus, we propose that intrachain disulfide bond formation precedes the association of class I heavy chain with beta 2m and peptide, and that disulfide bond formation is required for efficient assembly, ligand binding and folding of the class I heavy chain. PMID- 7783757 TI - Dynamical analysis of neuromuscular transmission jitter. AB - Utilizing prolonged axonal stimulation single fiber EMG, neuromuscular transmission becomes a time-series of interpotential intervals (IPIs). In this form, the underlying processes of neuromuscular transmission can be studied using standard numerical techniques to determine whether these processes can be described by a simple mathematical model. In particular, neuromuscular transmission jitter can be examined in this way. In this article, we attempt to determine whether healthy jitter is noise or deterministic chaos. The presence of deterministic chaos was assessed by analysis of the IPI time-series using visual inspection of both phase-space plots and their principal component dimensions, and using the Grassberger-Procaccia algorithm to determine the correlation dimension of the time-series dynamics. These graphical and mathematical techniques provided little evidence for the existence of deterministic chaos. Linear autoregression time-series prediction also failed to account for the variability of the data and IPI histograms exhibited simple gaussian distributions. These results suggest normal neuromuscular transmission jitter is the result of intrinsic noise. PMID- 7783758 TI - Neurological multisystem manifestation in multiple symmetric lipomatosis: a clinical and electrophysiological study. AB - Multiple symmetric lipomatosis (MSL) is characterized by a typical neck and shoulder distribution of subcutaneous lipomata and is often associated with polyneuropathy. Occasionally, the central nervous system (CNS) can be involved. Twelve of 14 patients in this retrospective study had clinical or electrophysiological evidence of a predominantly axonal polyneuropathy. Among those were 10 with alcohol abuse, but 2 patients without alcohol abuse also showed clinical or electrophysiological polyneuropathy. Clinical CNS involvement was present in 4 patients. CNS dysfunction was documented by evoked potentials in 8 subjects [prolonged latency or low amplitude of the motor response following cortical magnetic stimulation (4 patients), abnormal visually evoked potentials (4 patients) or somatosensory evoked potentials (SEP) (4 patients)]. These findings were compared to 10 chronic alcoholics without clinical signs of MSL. Five of these showed mild sensory neuropathy. Additionally, 2 also had delayed SEP latencies. Motor evoked potentials were normal in all controls. We propose that the multisystem involvement in MSL demonstrated here cannot be attributed to alcohol abuse alone. Biochemical studies have suggested mitochondrial dysfunction as the basis of the widespread neurological pathology in MSL. PMID- 7783759 TI - Dynamic electromyography and muscle biopsy changes in a 4-year follow-up: study of patients with a history of polio. AB - Eighteen patients who had had polio 29-56 years prior to the first investigation were studied on two occasions, 4 years apart. Isokinetic and isometric strength measurements and Macro EMG were performed in 28 legs. Muscle biopsy specimens were obtained on both occasions from 11 legs. On average the muscle strength was 56% of control values at the first examination, and decreased by another 8% during the observation period. The muscle fiber area was increased compared to that of controls and did not change significantly. Macro EMG, comprising muscle fiber area and number of muscle fibers, and/or single fiber EMG showed clear signs of reinnervation in all legs. The motor units at the first examination were increased 11-fold, on average, compared with age-matched control values. During the observation period, reinnervation continued and the size of motor units increased by another 56% as a result of ongoing denervation, that is, loss of neurons. This compensation was particularly pronounced in patients with stable conditions. The parameters studied did not reveal any definite pattern predicting future development of new muscle weakness in individual subjects. PMID- 7783760 TI - CT muscle imaging and the clinical assessment of neuromuscular disease. AB - Twenty patients with neurogenic disorders, polymyositis, or muscular dystrophies were assessed clinically and by CT imaging of limb, limb girdle, and trunk muscles, using a standard protocol. On each side of these patients 26 movements were graded by the MRC scale, and 20 muscles were assessed by CT imaging. The clinical and CT findings could be compared, in a blind evaluation, in 10 muscles on each side. A quantitative assessment of the CT muscle images were also made. The CT images showed striking abnormalities, even in many muscles of normal strength by clinical testing. Asymmetrical involvement of muscles was found in all the disorders studied, even when not suspected on clinical examination. Muscles in patients with muscular dystrophy were more abnormal than those in patients with neurogenic disorders. In polymyositis the attenuation values were intermediate to the other two groups. A "washed-out" appearance with very low attenuation values was very suggestive of muscular dystrophy. Involvement of paraspinal and rectus abdominis muscles was uncommon in neurogenic disorders. The gracilis muscle was relatively resistant to degeneration. CT imaging can enhance the clinical assessment of patients with neuromuscular disease, often revealing unexpected abnormalities. PMID- 7783761 TI - Lambert-Eaton myasthenic syndrome (LEMS) in association with lymphoproliferative disorders. AB - LEMS is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characteristic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after short maximal contraction or brief tetanic nerve stimulation. Here we describe 3 patients who had LEMS in association with lymphoproliferative disorder. The first patient had Castleman's syndrome with typical clinical and electrophysiological features of LEMS, which responded partially to treatment with 3-4-diaminopyridine. The second patient was a 7-year-old boy who had an unusual acute onset of LEMS associated with relapse of his Burkitt's leukemia. The third patient was a 60-year-old woman with non-Hodgkin's lymphoma. These 3 patients (together with 6 additional patients identified in the literature) lead us to suggest that lymphoproliferative diseases are another, hitherto unrecognized, type of malignancy associated with LEMS. Thus, any patient with these malignancies and unexplained muscle weakness should have electrophysiological evaluation for LEMS. PMID- 7783763 TI - Myophosphorylase deficiency associated with rhabdomyolysis and exercise intolerance in 6 related Charolais cattle. AB - A Charolais calf presented to the Veterinary Medical Teaching Hospital with a history of recumbency following forced exercise. The calf was unable to stand, and had severe rhabdomyolysis, dehydration, and electrolyte imbalance. Blood selenium concentrations were within normal limits. A complete absence of histochemical staining for phosphorylase was apparent in muscle biopsies. Five other animals in the herd also had exercise intolerance and had a complete absence of phosphorylase staining in muscle biopsies. Biochemical analyses confirmed a deficiency of myophosphorylase (range 0-0.3 mumol/g per minute: normals 15-27) with normal to slightly elevated muscle glycogen concentrations. Pedigrees from all affected animals showed a common ancestor on the sire's and dam's side of each phosphorylase-deficient animal, suggesting an autosomal recessive transmission. Although myophosphorylase deficiency was described in humans (McArdle's disease) over 40 years ago, these cattle represent the first animal model for this disease. PMID- 7783764 TI - Amyotrophic lateral sclerosis is a multifactorial disease. AB - Amyotrophic lateral sclerosis (ALS) is probably biphasic. An initial trigger(s) is followed by a terminal cascade coinciding with the onset of neurological deficits. The terminal cascade involves interactive multifactorial pathogenic mechanisms. Aging must play a crucial role leading to multiple defective or degraded gene products accumulating with progressing years. This in turn leads to failure of receptor integrity and resulting excitotoxicity, free radical accumulation, failure of neurotrophism, and possibly immunological disturbances. These events are predated by months or years by a trigger which is also likely to be multifactorial and cumulative. Evidence suggests that environmental factors may be important triggers. Failure of specific glutamate transporters and calcium binding proteins may account for selective vulnerability of the corticomotoneuronal system. It is postulated that in ALS the primary target cell is the corticomotoneuron or the local circuit interneurons which modulate its activity. Glia cells may play an important role in the demise of the corticomotoneuronal cell. The disordered corticomotoneuron induces excessive excitatory transmitter (glutamate?) release at the corticomotoneuronal-spinal motoneuronal synapse resulting in the subsequent demise of this neuron. PMID- 7783762 TI - Five-year experience in the treatment of focal movement disorders with low-dose Dysport botulinum toxin. AB - We report the results of botulinum toxin type A (Dysport, Porton Products, UK) treatment over 5 years in 107 patients with blepharospasm, Meige's syndrome, oromandibular dystonia, hemifacial spasm, cervical dystonia, and writer's cramp. Electromyography was used to localize dystonic muscles and guide Dysport injections in Meige's syndrome, oromandibular dystonia, cervical dystonia, and writer's cramp. All but 2 Meige's syndrome and 2 writer's cramp patients responded to treatment. Improvement was dramatic in blepharospasm (79%) and hemifacial spasm (90%); pronounced in cervical dystonia (74%); and moderate in Meige's syndrome (53%), oromandibular dystonia (57%), and writer's cramp (34%). Although Dysport doses were 50-75% lower than usually reported, response and improvement rates as well as relapse intervals were similar to those of others. To treat cervical dystonia relapses, only 50% of the initial dose was required for continued optimal relief of symptoms. Low-dose Dysport was associated with a very low incidence of dysphagia in cervical dystonia. PMID- 7783765 TI - Mitochondrial encephalomyopathy with autosomal dominant inheritance: a clinical and genetic entity of mitochondrial diseases. AB - We report a Japanese family with chronic progressive external ophthalmoplegia (CPEO) with autosomal dominant inheritance, and review 54 reported CPEO patients in seven families (including the present family) with autosomal dominant inheritance and mtDNA deletions in the skeletal muscle. Mean age at onset in the CPEO was 26 years, which is older than that in published solitary cases. In addition to blepharoptosis and external opthalmoplegia, proximal muscle atrophy and weakness were found in 62%, hearing loss in 25%, and ataxia in 17% of the patients. Retinal degeneration was not found, and cardiac involvement was very rare. mtDNA deletions in the muscle were multiple and large scale, and all such deletions were located in the non-D-loop region. Autosomal dominant CPEO has unique clinical features which differ from those of solitary CPEO, and is associated with multiple large-scale mtDNA deletions. Thus, autosomal dominant CPEO can be considered a clinical and genetic entity of mitochondrial diseases. PMID- 7783766 TI - Limited longitudinal sliding of the median nerve in patients with carpal tunnel syndrome. AB - During normal movements or changes in position of the limbs, nerve structures must accommodate the resulting changes in length of the nerve path. In patients with carpal tunnel syndrome, we monitored electrophysiologically the longitudinal adjustment of the median nerve to positions of extreme flexion and extreme extension of the wrist and elbow, by measuring the differences induced in the latency of the sensory nerve action potential (SNAP) recorded in the forearm and upper arm. In patients, the latency difference was significantly shorter than in normal subjects (0.196 +/- 0.084 ms vs. 0.088 +/- 0.059 ms in the forearm, and 0.485 +/- 0.122 ms vs. 0.129 +/- 0.086 ms in the upper arm). These results indicate that the displacement of the source of the median nerve SNAP with movements of flexion and extension is limited in patients with carpal tunnel syndrome. Such an abnormality may partly underlie the pathophysiology of entrapment syndromes. PMID- 7783767 TI - Paradoxical heat sensation in uremic polyneuropathy. AB - Sensory aspects of uremic neuropathy were studied in 36 patients using clinical assessment and quantitative sensory tests (QST). The outstanding abnormality in sensory quality was perception of heat in response to low temperature stimuli. This paradoxical heat sensation was found in the foot in 42% (15) of patients, far beyond the normal prevalence of 10%. Paradoxical sensation was positively related to cold hypoesthesia (P = 0.0004) suggesting disinhibition as a possible mechanism. Paradoxical heat sensation also positively related to creatinine level (P = 0.0012). Pruritus was present in 20 patients (56%), intensity not related to any biochemical or clinical parameter. Signs of sensory polyneuropathy (PNP), based on at least two abnormal parameters in the clinical assessment or QST, were found in 39% of patients (14), of whom 11 had paradoxical heat sensation. Thus, in 4 patients (11%), this sensory aberration preceded other signs for PNP. Paradoxical heat sensation seems to be a common and often early expression of the sensory neuropathy in uremia. PMID- 7783769 TI - Proximal myotonic myopathy syndrome in the absence of trinucleotide repeat expansions. PMID- 7783768 TI - Cerebrospinal fluid and serum from patients with inflammatory polyradiculoneuropathy have opposite effects on sodium channels. AB - The effects of cerebrospinal fluid (CSF) and serum from patients having Guillain Barre syndrome (GBS) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on voltage-dependent Na+ channels were compared. Bathing human myoballs in CSF substantially reduced their Na+ currents (by > 40% with 8 of 10 patients) elicited at 1 Hz under whole-cell recording conditions. This was because, at the resting potential, more Na+ channels were inactivated (left-shift of the h infinity curve). CSF from patients with other neurological diseases (OND) produces a similar, but smaller, effect. In contrast, serum samples from the same GBS and OND patients caused an increase of the Na+ currents by reducing the number of Na+ channels inactivated at the resting potential. This right-shift of the h infinity curve is in part explained by the effect of serum albumin. We confirm that the CSF of most GBS and CIDP patients contains factors inhibiting voltage-dependent Na+ currents. There is no indication that such factors are effective in the serum of these patients. PMID- 7783770 TI - Evidence for low production of lactate and pyruvate in alcoholic rhabdomyolysis. PMID- 7783771 TI - F-wave quantitation in neuropathy (a reply) PMID- 7783773 TI - Electrophysiological assessment of functional corpus callosum integrity in internal hydrocephalus. PMID- 7783774 TI - Electrodiagnosis in the management of focal neuropathies: the "wog" syndrome. PMID- 7783775 TI - Assessment of variability in the shape of the motor unit action potential, "the jiggle," at consecutive discharges. PMID- 7783772 TI - On the myofascial origin of muscle cramps. PMID- 7783776 TI - Sciatic nerve impingement from piriformis hematoma due to prolonged labor. PMID- 7783777 TI - Tarsal tunnel revisited. PMID- 7783778 TI - Effect of processing on the composition of dietary fibre and starch in some legumes. AB - The effect of processing on the total dietary fibre (TDF) insoluble (IDF) and water-soluble (SDF) fractions as well as total (TS), available (AS) and resistant (RS) starch were studied in three legumes, viz. bengalgram (Cicer arietinum L.), Cowpea (Vigna unguiculata) and greengram (Vigna radiata). The processes studied were fermentation, germination, pressure-cooking and roasting. The dietary fibre (DF) content and its components were determined using the enzymatic-gravimetric method. The TS content was determined by the enzymatic method after solubilization with KOH. The DF content ranged from 23.2 to 25.6 g/100 g in the raw and 16.0 to 31.5 g/100 g in the processed legumes. All the processing treatments significantly decreased the SDF content and increased the IDF content of all the three legumes. The mean TS, AS and RS content of the raw legumes were similar, 46.9, 36.7 and 10.2 g/100 g respectively. AS content of all the legumes was reduced by the processing treatments, except pressure cooking. Correspondingly, higher amounts of RS were observed in the processed legumes, except pressure cooked, resulting in an increase in the TDF content. PMID- 7783779 TI - [The quantitative determination of the protein content of milk by means of violet spectral photometry. 7. The milk analyzer MAG 100 (Carl Zeiss Jena GmbH)--a possibility for simultaneous measurement of protein and fat content in raw milk at the dairy farm]. AB - A new analysing apparatus is introduced, which allows to measure protein and fat contents of milk in the dairy farm. The instrument works on the basis of ultraviolet spectral photometry. Before measuring the milk sample must be diluted with a hydrous detergent solution in the ratio 1:100 and then homogenized. Accuracy and precision of the analytic results are influenced by detergent type, the water quality of detergent solution, the detergent foam, the air content and the pH of detergent solution, the reliability of homogenizer and thermostating system, the stability of photometer and by the error of dosage. Also a milk standard was developed, which is required for daily calibration of the apparatus. PMID- 7783780 TI - Evaluation of functional properties of offal proteins. AB - Evaluation of functional properties of beef heart and lip tissue proteins was based on the data obtained in the following determinations: protein extractability, fat emulsifying capacity, emulsion stability, gel forming ability, and water holding capacity after heat treatment. Beef skeletal muscles were used as the control. It was found that extractability of proteins of the raw materials was low as well as their ability to stabilize emulsions was on a low level. Proteins soluble at high ionic strength (fraction HIS) of beef heart and lip tissue emulsified 80.7 ml and 68.9 ml of oil/100mg of protein, respectively, as compared to 106.6 ml in the control group. Analogically, protein soluble at low ionic strength (fraction LIS) emulsified 77.9 ml, 61.2 ml and 100.4 ml of oil, respectively. Emulsion stability of offal proteins appeared to be dependent on ionic strength. Generally at higher concentrations of salt their ability to stabilize emulsions was better as well as their water holding capacity increased. Their gelation properties as compared to control were also low. In each case, the functionality of cardiac proteins proved to be better than that of beef lip tissue. PMID- 7783782 TI - Content of some metals in mean tissue of salt-water and fresh-water fish and in their products. AB - The main goal of this work was to determine the concentration of some metals in meat tissue of salt-water and fresh-water fish and in their products. These studies refer to 13 species of fish most often eaten in Poland, caught in 1992. Fish (samples) for testing and examination were taken from each species once every month during the term of 6 months. The lead content in tested fish and their products did not exceed the set limits (0.6 mg Pb/kg), which were exceeded only in preserve from oyster. The average content of cadmium in flounder, Alaska pollack, Baltic herring, pickled herring pieces and in preserves with shrimp, crab and oyster exceeded the set limits (0.05 mg Cd/kg). The copper and zinc content in tested fish and their products is also within the set domestic limits (10.0 mg Cu/kg and 50.0 mg Zn/kg). The iron (3.6-24.2 mg/kg), magnesium (170-380 mg/kg) and manganese (0.12-0.31 mg/kg) contents in muscle tissue of the tested fish and their products seem to be typical. The presence of absolutely toxic metals (lead and cadmium) in some species of fish and their products points to extreme contamination of water environment by those metals. PMID- 7783781 TI - Influence of harvesting and drying techniques on microflora and mycotoxin contamination of figs. AB - Mould growth and mycotoxin (aflatoxins and ochratoxin A) formation were examined in the 1993 dried figs crop. The relationships between mould/mycotoxin contamination and orchard conditions, different harvesting techniques, harvesting time and intactness of fruits were investigated. The fruits were examined during drying and effects of different pretreatments, sun drying and solar drying on the mould and mycotoxin contamination in figs were also studied. Aflatoxins (B1, B2, G1 and G2) were not present in the firm or shrivelled ripe figs. Among the samples examined during drying, only one of the 32 samples was found to be aflatoxin positive. Ochratoxin A was not detected in any of the samples analysed. The moisture content, aw and pH values of full ripe and shrivelled fruits were suitable for mould growth and mycotoxin formation while these parameters in pretreated and dried fruits were found to be too low to allow such outcome. It was observed that harvesting the fruit by hand-treating with different solutions and application of solar drying were effective in reducing contamination level. PMID- 7783783 TI - [The psychophysics of sweet taste. 6. Context effects by use of multiple stimuli sequences]. AB - For the determination of differentiation probabilities in a multiple experimental design the range of stimuli is a significant source of disturbance. In order to determine their efficiency, sequences with 5 equidistant gradated concentrations of sucrose were used, which were compared with a basic concentration. The probability for each gradation was carried out with help of 2-AFC-technique (60 pairs each). 5 gradations at 3 basic concentrations with fixed, average balance were examined in a factorized experimental design. The frequency of the correct judgments is linearily dependent on the sequence of stimuli. In the experimental space the slope of this relationships decreases with increasing gradation hyperbolically (range-effects). The level of the basic stimuli is in this view without any greater importance. When determining the difference thresholds these context effects are to be considered. PMID- 7783784 TI - On carrots and sticks, and honey and vinegar. PMID- 7783785 TI - An interview with Sandra C. Matherly and Shannon Hodges. Interview by Connie C. Curran. AB - Sandra C. Matherly, MA, RNC, FNP, is senior vice president, business development, and Shannon Hodges, MBA, is vice president, clinical development, Nurse On Call, Inc., Norcross, GA. Founded in 1993, Nurse on Call is a software and services company offering nursing, medical, and business expertise in setting up and operating a patient management unit using telecommunications and information systems. In this interview, Ms. Matherly and Ms. Hodges discuss the history and development of Nurse on Call, and offer advice for starting a successful nurse entrepreneur enterprise. PMID- 7783786 TI - A cost-effectiveness analysis of acute care case management outcomes. AB - Case management was more cost effective in a moderately uncertain practice environment than in either a low or a high uncertainty environment. The environmental state, case manager role differentiation, and information coordination contributed most strongly to these outcomes. PMID- 7783787 TI - Economic pressures building in the hospital employed RN labor market. AB - Over the past several years, a number of powerful forces have rapidly changed hospitals' operating environment. Other forces, stemming from changes in the nation's economy and the debate over health care reform, have directly influenced RNs' employment activity. The hospital RN labor market has responded quickly and hospitals no longer face RN shortages. PMID- 7783788 TI - A decentralized model for case management. AB - Case management has been implemented in a variety of health care settings. The implementation of case management at one hospital, including rationale for selection and outcomes, is described here. A decentralized model emphasizing staff nurse control is recommended for hospitals with TQM and shared governance programs already in place. PMID- 7783789 TI - Dimensions of the staff nurse role in ambulatory care: Part II--Comparison of role dimensions in four ambulatory settings. AB - Ambulatory care nursing is one of the fastest growing and least studied areas of nursing practice. Information from a national survey of ambulatory nurses has been used to delineate the core dimensions of the current staff nurse role. Comparison of practice patterns of ambulatory staff nurses employed in university hospitals, community hospitals, physician group practices, and health maintenance organizations can provide insights for nurse managers interested in improving ambulatory nursing care delivery. Part III of this series, which will be published in the July/August 1995 issue, will examine how to use research data to design new models of nursing care delivery. PMID- 7783790 TI - Stage managing change: supporting new patient care models. AB - The scope and accelerated pace of change is providing high drama in health care organizations today. The Central DuPage Hospital experience of transitioning to patient-focused care was driven by aggressive targets and tight timelines. Providing practical, adaptable change management strategies to key players ensured a well-staged transition to the new models of patient care. PMID- 7783791 TI - Reducing specialty bed use. AB - Saint Joseph Hospital is a tertiary care teaching facility with 602 licensed beds. In 1992 it was noted that there was a significant rise in the use of specialty beds within the hospital. Guidelines for selection, initiation, and termination were nonexistent. In an effort to reduce high costs associated with specialty bed use a study was conducted to determine appropriate selection criteria and monitor patient outcomes. PMID- 7783793 TI - Re-engineered out of your job: what next? PMID- 7783792 TI - Managing your career as a contingent worker: the nurse manager's challenge. PMID- 7783794 TI - A bad month? PMID- 7783796 TI - Medicare at risk: to whose benefit? PMID- 7783797 TI - [Current treatment of Hirschsprung disease: the end of the stoma period]. PMID- 7783798 TI - [Oral contraception increases the chance of venous thrombosis in factor V Leiden mutation]. PMID- 7783795 TI - Managed care 'marriage' benefits perioperative nursing. PMID- 7783799 TI - [Display screens, eye symptoms, eyeglasses]. PMID- 7783800 TI - [Diagnosis of lymph node metastasis of head-neck carcinomas]. PMID- 7783801 TI - [Shortage of lung donors: 3-year experience in the Groningen Academic Hospital]. AB - OBJECTIVE: To analyse the background of the shortage of donor lungs; to present the procedure of allocation of donor lungs in the Eurotransplant region and the selection of donor lungs in the lung transplantation programme Groningen. DESIGN: Descriptive. SETTING: Groningen University Hospital. METHODS: From March 23, 1991 to December 31, 1993, the lungs of 279 multi-organ donors were offered to the lung transplantation programme of Groningen University Hospital. The assessment and selection criteria are presented. RESULTS: Only 35 out of all donor lungs offered could be used for transplantation: 24 double and 11 single lung transplants. Medical contraindications (notably pulmonary injury and hypoxaemia) were present in 155 out of the 244 (64%) lung donors. Forty-five out of 244 (18%) lung donors were rejected for logistic reasons, predominantly too little time between offer and imposed start of the explantation or long travel time. CONCLUSION: Lung donor shortage is the main factor limiting the expansion of lung transplantation programmes. Increase of the number of suitable donors can be achieved by improving donor recognition and donor management, and by improving preservation techniques allowing increased acceptable cold ischaemia periods. PMID- 7783803 TI - [Vaginal infection caused by Saccharomyces cerevisiae]. AB - In a woman of 26, who suffered from a vulvovaginal infection and had previously been treated for Candida vaginitis, Saccharomyces cerevisiae was cultured and identified. At her work she sold baking yeast. Topical treatment with amphotericin B 100 mg suppositories was successful. Microscopic examination (1000 x) of the discharge in saline showed haloed yeast cells. For treatment, oral ketoconazole or topical administration of amphotericin B or clotrimazole, in relatively high doses, may be applied. This yeast might be the cause of 'chronic candidiasis' more often than suspected, notably in women working in a bakery or a brewery. PMID- 7783802 TI - [Drug use by mentally handicapped persons in institutions and family-replacing residential facilities]. AB - OBJECTIVE: Description of use of medication by people with mental handicaps in relation to age, level of mental handicap and living facility. DESIGN: Cross sectional study. SETTING: Institutions and group homes for people with mental handicaps in North Brabant and Limburg, the Netherlands. METHODS: Of a patient sample (n = 1265), stratified according to age and living facility (i.e. institution or group home) data were collected by means of questionnaires to be completed by the general practitioners. For 101 persons data about level of mental handicap were lacking. RESULTS: 57% of the patients used one or more drugs. The numbers of drugs used were significantly related to (increased) age and level of mental handicap. Older patients more often used antipsychotics, laxatives and cardiovascular medication, younger ones more often used anticonvulsants. More severely handicapped persons used antipsychotics, anticonvulsants, laxatives, antacids, psychoactive medication and gastrointestinal medication more often. There was no relationship between amount of medication and living facility. CONCLUSION: Many mentally handicapped use medication. Since epilepsy, psychiatric and behavioural diseases and gastrointestinal problems are frequent, and because the patients offer little spontaneous information, alertness with respect to drug interaction and side effects is indicated. PMID- 7783804 TI - [From the library of the Nederlands Tijdschrift voor Geneeskunde: Conservandae sanitatis praecepta saluberrima: hygiene according to the Salerno School]. PMID- 7783805 TI - [Gastroesophageal reflux in infants; recommendations for diagnosis and treatment]. PMID- 7783807 TI - [Are supplemental studies always a supplement in suspected paradoxical embolism?]. PMID- 7783806 TI - [Marginal notes on esophageal pH measurement in the diagnosis of gastroesophageal reflux in children]. PMID- 7783808 TI - [Are supplemental studies always a supplement in suspected paradoxical embolism?]. PMID- 7783809 TI - [Retrobulbar hemorrhage]. PMID- 7783811 TI - [The status of transcranial color-coded real time ultrasound in diagnosis of cerebral lesions]. AB - Transcranial color-coded real-time sonography (TCCS) combines transcranial Doppler sonography and color-coded B-mode scanning of the brain parenchyma and cerebral vessels. This technique is not invasive and a broad spectrum of intracerebral lesions such as vascular lesions (ischemic stroke and intracerebral hemorrhage, aneurysms, arteriovenous malformations, arteriosclerotic vascular degeneration) and parenchymal lesions (brain tumors, degenerative and neuropsychiatric disorders) can be disclosed. Compared with MRI and CT, the ultrasound system is movable. Thus, it can be used easily in emergency rooms and intensive care units. In addition, TCCS can disclose new insights into the pathophysiology of disorders of the CNS, as in neuropsychiatric diseases. Ultrasound contrast agents improve the depiction of intracranial vessels. The pathology of the venous system can be identified. PMID- 7783812 TI - [Photographic pupil diagnosis in Horner syndrome]. AB - In cases of miosis without other clinical signs and not contributory medical history it is often hard to differentiate Horner's syndrome. In these cases the pharmacological testing with cocaine eye drops is a well established and validated method. The physiological testing, i.e. the detection and measurement of a dilatation lag in Horner's syndrome, is not so common. For this reason we measured the dilatation of pupils in 22 Horner's syndromes and 16 physiological anisocorias to find limit ("cut off") values. We used flash photography and a commercial available camcorder and took photos in bright light (400 cd/m2) as well as 4 and 15 seconds after cessation of light stimulus in darkness. An anisocoria after 4 seconds of darkness greater than 0.6 mm distinguishes both groups with a sensitivity of 82% and a specifity of 69%. A dilatation speed of the smaller pupil during the first 4 seconds of darkness lower than 1.1 mm/4 sec is also a good threshold value. Because of the additional good correlation of these parameters to the anisocoria after cocaine the photographic methods are at least a supplement to pharmacological testing with cocaine, which is sometimes equivocal and always delays the localizing hydroxyamphetamine test. The advantage of using a camcorder is the immediate evaluation on a TV screen. Because of the similar price it is more useful to buy an infrared camera to perform real pupillography. Because of the missing possibility of magnification we prefer the evaluation of slides instead of Polaroid flash photographs. PMID- 7783810 TI - [Electroconvulsive therapy in neurologic diseases]. AB - Numerous developments have improved the safety and efficacy of electroconvulsive therapy (ECT) in recent years, so that ECT is now one of the safest forms of treatment under anesthesia. The indications for psychiatric patients are clearly defined. ECT is also under discussion with respect to certain neurological disorders. This discussion has, however, been largely ignored by the German medical profession. Critical evaluation of previous experience, especially in the United States and in Scandinavia, reveals some clinical situations (e.g., akinetic crisis in Parkinson's disease) in which a primary neurological indication for ECT might be present. ECT is frequently indicated in other brain diseases if pronounced psychopathological disturbances (especially of a depressive type) occur and fail to respond to conventional treatment with psychotropic drugs. ECT may then be indicated on a case-by-case basis. ECT should not be withheld from such patients; on the other hand, there is the risk of uncontrolled expansion of these indications for ECT. PMID- 7783813 TI - [Infarcts in the brain areas supplied by the posterior cerebral artery. Clinical aspects, pathogenesis and prognosis]. AB - The clinical and neuroradiological features of 127 patients with ischemia of the posterior cerebral artery (PCA) and a positive CT scan (n = 122) or pathological angiography findings (n = 63) were analyzed. Unilateral headache was the most common presenting symptom (50%), making complicated migraine an important differential diagnosis. Clinical findings were visual field deficits (93%), sensory (29%), motor (28%), and neuropsychological deficits (25%). Infarcts, including the thalamus (n = 27), were mostly associated with sensory and slight motor deficits. Our findings suggest that motor deficits in PCA ischemia, particularly if minor and reversible, are likely to be due to ischemia-induced edema in the internal capsule adjacent to an associated thalamic infarct. Based on angiography, stroke etiology was considered embolic in 83/127 (65%), atherothrombotic in 20/126 (16%), and probably migrainous in 4 (3%) patients. In the remaining 20 patients (16%), the etiology was uncertain. Prognosis of PCA infarcts is usually good. PMID- 7783814 TI - [Local thrombolytic treatment of spontaneous intracerebral hemorrhage with plasminogen activator (rt-PA). Indications and limits]. AB - Twenty patients underwent a regimen of stereotactic puncture and consecutive local lysis with recombinant tissue plasminogen activator (rt-PA) for their spontaneous intracerebral hemorrhage (ICH). Rt-PA was administered via a stereotactically placed silicone catheter according to a hematoma-size-related formula. There was no extensive intraoperative hematoma aspiration so that the capacity of rt-PA for blood-clot lysis could be investigated. Fifteen patients were somnolent/stuporous on admission and 5 comatose, the hematoma-size ranging from 3 x 3 x 4 cm up to 7 x 4 x 4 cm (mean: 5.1 x 3.9 x 3.5 cm). Control computed tomography (CT) was performed on a daily basis, and in 19 patients the hematoma showed complete or almost complete resolution on CT within 4 days. The rt-PA dosage necessary ranged from 5 to 14 (mean: 8.5) mg. Rt-PA application was performed once in 1 patients, twice in 7, three times in 11 and four times in 1 patient. On follow-up after a mean of 7.2 months 3 patients had died (Glasgow Outcome Score--GOS I). Another was GOS II, 10 GOS III, 5 GOS IV and 1 had made an excellent recovery (GOS V). Patients who were somnolent or stuporous on admission or who exhibited secondary deterioration of their level of consciousness benefitted from the treatment protocol. Early postoperative mobilization and thereby reduction of secondary complications during the patient's stay in the intensive care unit appear to be possible. Comatose patients did not benefit from this treatment and those should be treated conservatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783816 TI - [Adenomatous hypophyseal apoplexy. Clinical, diagnostic and therapeutic aspects of a frequently misdiagnosed emergency state]. AB - Pituitary adenoma apoplexy was considered an acute life-threatening condition until more benign and even asymptomatic courses were found by advanced neuroimaging procedures. Necrosis and hemorrhage in the pituitary adenoma can cause acute enlargement of the tumor. sometimes with rupture of the tumor capsule and bleeding into the subarachnoid space and surrounding parts of the brain. Clinical symptoms include acute or subacute headache in combination with signs of meningeal irritation and neuroophthalmological and cerebral dysfunction. Severe panhypopituitarism may be an additional complication. Acute blindness due to compression of the optic chiasm and symptomatic compression of basal cerebral arteries require immediate transsphenoid tumor resection. If panhypopituitarism is suspected, immediate hormone substitution is necessary. PMID- 7783817 TI - [Differential therapeutic aspects in treatment of obstructive sleep apnea syndrome]. AB - We report the case of a 43-year-old man who suffered from obstructive sleep apnea with excessive daytime sleepiness and nocturnal sweating. His initial apnea index of 60/h improved under treatment with an Esmarch device. Apneas were totally suppressed by nCPAP application with a pressure of only 4 mb, but the patient rejected nCPAP therapy. After two years with the Esmarch device he reported increasing temporomandibular joint pain and Esmarch therapy had to be stopped. A cephalometric evaluation showed good prognosis for maxillomandibular advancement osteotomy, which was performed and which suppressed the apneas completely over a period of more than one year. Indication, surgical technique, and risks are discussed. PMID- 7783818 TI - [Cladribine in chronic progressive multiple sclerosis]. PMID- 7783819 TI - [Current therapy of multiple sclerosis: are there indications for intravenous immunoglobulins?]. PMID- 7783815 TI - [The idiopathic QT syndrome as the cause of epileptic and nonepileptic seizures]. AB - The long QT syndrome (LQTS) is characterized by a pathological lengthening of the corrected QT interval on the surface ECG and the occurrence of syncopal attacks, sometimes presenting as a seizure disorder. They are caused by ventricular tachycardia of the torsade de pointes type, an arrhythmia that is also responsible for the high incidence of sudden death among these patients. Besides the acquired forms of LQTS which are transient (e.g. therapy with QT-prolonging drugs), congenital variants (Romano-Ward syndrome, Jervell/Lange-Nielsen syndrome, sporadic form) can occur as well. The latter mostly become manifest during childhood or adolescence. Because the syndrome is rare, it is often not included in the primary differential diagnosis of syncope. Thus, misinterpretation as epilepsy may occur. Especially if siblings are affected, a genetic epilepsy may be diagnosed. However, the correct diagnosis can be made by standard ECG methods. Early recognition of the syndrome is very importance because of prognostic and therapeutic consequences. In this article, two cases of idiopathic LQTS are presented. Problems regarding differential diagnosis and therapy are discussed. PMID- 7783820 TI - [Phobic vertigo. A panic disorder--or?]. PMID- 7783821 TI - The position of theophylline in the treatment of asthma and chronic obstructive pulmonary disease. PMID- 7783822 TI - Acute pernicious or fulminating beriberi heart disease. A report of 6 patients. AB - OBJECTIVE: To investigate the incidence and presentation of acute pernicious or fulminating beriberi in a general district hospital. METHODS: All patients with a diagnosis of acute pernicious or fulminating beriberi heart disease made between 1978 and 1994 were identified, and their medical records were retrospectively examined. RESULTS: Six cases of acute pernicious or fulminating beriberi heart disease were recognized. The disease was characterized by circulatory shock and peripheral cyanosis. All patients had severe lactic acidosis, in 5 of them without hypoxaemia. Four patients were alcoholics. The most important diagnostic criterion was the impressive improvement after thiamine administration. CONCLUSIONS: Acute pernicious or fulminating beriberi heart disease can be recognized occasionally. Thiamine should be administered as soon as possible in suspected cases. PMID- 7783823 TI - CAPD patients exhibit a nocturnal fall in blood pressure: a single-centre study. AB - BACKGROUND: In 29 CAPD (continuous ambulatory peritoneal dialysis) patients the height and diurnal variation of the blood pressure (BP) and heart-rate (HR) were analyzed by means of 24-hour ambulatory blood pressure monitoring (ABPM). METHODS: Normal diurnal variation was defined as a fall of 10% or more during nighttime (NT) compared with daytime (DT) BP or HR (DT = 10.00 a.m.-9.00 p.m., NT = midnight-06.00 a.m.). To evaluate high BP in the course of time we used the concept of "whole-day BP load", defined as the percentage of BP readings above 140/90 mmHg during a 24-h period. A "hypertensive BP load" was defined as a systolic BP (SBP) load of more than 50% and/or a diastolic BP (DBP) load in excess of 40%. In addition to analysis of the circadian rhythm of BP and HR and the prevalence of a hypertensive BP load in CAPD patients, the influence of various factors such as gender, creatinine clearance, recombinant human erythropoietin, antihypertensive medication, haematocrit, whole-day BP load, and the nightly dialysis glucose concentration on the diurnal variation of BP and HR were studied. RESULTS: Based on the 95% confidence intervals for the proportional nocturnal decrease, normal diurnal variation of BP and HR was present in most CAPD patients. No correlation could be demonstrated between a blunted circadian rhythm and the variables mentioned above. However, when other time-period definitions (DT = 6.00 a.m.-11.00 p.m., NT = 11.00-6.00 and DT = 8.00 a.m.-8.00 p.m., NT = 8.00 p.m.-8.00 a.m.) were applied to the data, considerably fewer patients displayed normal diurnal variation. Whereas all patients showed normal home BP readings, ABPM of 21 out of 29 patients displayed a hypertensive BP load. CONCLUSION: The majority of our CAPD patients exhibited normal diurnal variation of SBP and DBP depending, however, on the definitions of DT and NT used. The absence of a normal circadian rhythm could not be explained by any of the variables analyzed. Surprisingly, uncontrolled hypertension, as defined by a hypertensive BP load, was found in 72% of the patients. PMID- 7783824 TI - The choriocarcinoma syndrome: an emergency. AB - A 36-year-old male patient is described who presented with gynaecomastia, pulmonary nodules and a retroperitoneal mass in combination with a markedly elevated HCG level. A diagnosis of "choriocarcinoma syndrome" was made. Despite a clear response from the tumour to chemotherapy the patient died, at least partially due to delay in treatment. Prompt treatment even without cytological or histological proof is therefore stressed. PMID- 7783825 TI - Urethral stricture as unusual complications of Wegener's granulomatosis. AB - A patient with Wegener's granulomatosis is reported. The diagnosis was confirmed by parotid gland biopsy. The patient responded to treatment with cyclophosphamide and prednisone. After many years, urethral stricture and subglottic stenosis developed and responded satisfactorily to surgery. PMID- 7783826 TI - Interference of MIBG uptake by medication: a case report. AB - Phaeochromocytoma is one of the causes of hypertension. Topographic diagnosis is made by CT-scans or scanning with 123I- or 131I-metaiodobenzylguanidine (123I- or 131I-MIBG). We describe a patient with recurrent episodes of severe hypertension and increased serum catecholamines. With the suspicion of a phaeochromocytoma labetalol was given. Subsequently the 123I-MIBG scan showed an abnormal distribution of MIBG. After discontinuation of labetalol therapy the biodistribution of 123I-MIBG returned to normal. A list of drugs known and one drug which may be expected to interfere with MIBG scintigraphy are appended. It seems advisable to discontinue labetalol and other medication that may interfere with MIBG for at least several days before administering MIBG. PMID- 7783828 TI - Computer assistance in the practice of internal medicine. AB - An overview is given of the possibilities of electronic support in the practice of internal medicine and of the preferred electronic environment in the hospital. For efficient exchange of information, mutual cooperation between all departments and medical specialists in the hospital is of great importance. The development of a sufficient hospital information system has to start with the composition of an information design, based on the concept of an open hospital database with connections to subsystems of the different departments and medical specialisms. Within this design basic, organizational, management and (medical) knowledge providing programs can be applied. General, medical, scientific and organizational aspects of electronic support in internal medicine are discussed with some practical examples. A brief comment is made on the necessity of using code numbers for diagnoses. PMID- 7783827 TI - Hyperhomocysteinaemia: a role in the accelerated atherogenesis of chronic renal failure? AB - Moderate hyperhomocysteinaemia has recently been established as an independent risk factor for atherothrombotic disease. It might be caused by heterozygosity for cystathionine beta-synthase deficiency, an enzyme involved in the conversion of methionine to cysteine through the transsulphuration pathway or by inherited thermolability of the enzyme which remethylates homocysteine into methionine. In chronic renal failure (CRF) homocysteine levels are significantly elevated at a relatively early stage. The normal kidney possibly plays an important role in homocysteine catabolism, which cannot be performed in CRF. Alternatively, decreased extrarenal catabolism can contribute to the hyperhomocysteinaemia in this disease state. Treatment with folic acid, 5 mg daily, significantly lowers homocysteine levels in chronic renal patients. PMID- 7783829 TI - [Viral hepatitis C and membranoproliferative glomerulonephritis in a renal transplant patient]. AB - We report the case of a 36 year-old-patient, hemodialyzed for idiopathic membranous glomerulonephritis, who suffers from type I membranoproliferative glomerulonephritis five years after a successful kidney transplantation. Etiologic evaluation evidenced chronic viral hepatitis C complicated by type III cryoglobulinemia. If hepatitis C induced membranoproliferative glomerulonephritis has yet been described among non transplanted patients, it is at our knowledge, the first observation in a renal transplant recipient. PMID- 7783830 TI - [Nasal carriage of Staphylococcus aureus: prevalence in a hemodialysis center and effect on bacteremia]. AB - We evaluated nasal carriage of Staphylococcus aureus (S. aureus) in 114 hemodialysis patients by performing two nasal swab cultures at a one month interval. The incidence of bacteremia was then followed for one year. Other factors associated with infections in hemodialysis patients, such as diabetes, central venous catheter, and high serum ferritin levels were also evaluated. Nasal carriage of S. aureus was present in 29.8% of patients (34/114). Six S. aureus bacteremia occurred in 6 patients. This represents an annual incidence of 0.058 bacteremia/patient-year. The incidence of bacteremia was higher in patients with S. aureus nasal carriage (0.0945) than in patients without (0.0417), but the difference was not significant. The relative risk (RR) was 2.35. On the contrary, bacteremia were significantly more frequent in patients with diabetes (RR = 11.41; p = 0.004) or in patients with central venous catheter (RR = 14.29; p = 0.002). In conclusion, in our population, diabetes and central venous catheter are more significant risk factors of bacteriemia than S. aureus nasal carriage. PMID- 7783831 TI - [Anticancer chemotherapy. Prescription in the presence of renal insufficiency]. PMID- 7783833 TI - [Production of IFN gamma, IL6 and IL10 by infiltrating cells of renal allografts and irreversible rejection: modulation by IL2 and IL4]. AB - The frequency of isolated low density graft-infiltrating cells (GIC) secreting IFN gamma, IL6 and IL10 was studied in 8 cases of irreversible rejection of human renal allografts, using ELISPOT assays. The GIC were mostly CD8+ T cells although CD4+ T cells, B cells and macrophages could also be detected. In average, in 10(6) cells, 189 secreted IFN gamma, 747 IL10, and 17,114 IL6. Culture of GIC in the presence of IL2 resulted in an increase on the frequency of IFN gamma producing cells (IFN gamma-PC), in a dose dependent manner, with an optimal 6.5 fold increase at 50 U/ml. In contrast, 25 U/ml IL4 decreased the frequency of spontaneous and IL2 induced IFN gamma-PC. Furthermore, IL4 reduced the frequency of IL6-PC. PMID- 7783832 TI - [Lymphocyte adhesion of human peripheral blood to aortic endothelial cells of a porcine xenograft: preferential adhesion to NK CD3-CD16+ cells]. AB - Xenotransplantation, the transplantation of tissues or organs between species find renewal interest because of human organ shortage. As the xenogeneic transplantation leads immediately to an humoral mediated rejection with graft necrosis, the study of the cellular response is not possible in vivo. So we developed an in vitro model to study the adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC). We showed that PBL were able to bind to PAEC, and that this adhesion was increased when PAEC were stimulated with human recombinant TNF-alpha. The action of TNF-alpha is maximal when PAEC were stimulated during 6 hours with 100 U/ml TNF-alpha. This adhesion involved preferentially CD3-CD16+ NK cells compared with CD3+CD16- T lymphocytes. Finally monoclonal antibodies directed against PBL adhesion molecules decreased PBL adhesion to PAEC. PBL adhesion to PAEC would be a first step in a cellular mediated rejection in xenotransplantation. PMID- 7783834 TI - [Bourneville's tuberous sclerosis (BTS) and nephrocalcinosis]. PMID- 7783835 TI - Baclofen is cytoprotective to cerebral ischemia in gerbils. AB - The release of the neurotransmitter, glutamate, and the activation of receptor operated calcium channels, may increase the degree of damage in ischemic brain tissue. Inhibition of excitatory neurotransmitters should therefore result in cytoprotection of ischemic brain tissue. In this study we evaluated the effect of baclofen, an inhibitor of presynaptic glutamate release, on ischemic gerbil cortex, hippocampus (CA 1 and CA4), striatum and thalamus. Histological evaluation was done in a blind manner in 4 groups (total 36 animals): a control group (9 animals) and three groups (27 animals) with varying doses of baclofen. For cerebral ischemia, we used single episode of five minutes of arterial occlusion of the carotid arteries. Baclofen in doses of 0, 25, 50, and 100 mg/kg were given to different groups five minutes prior to ischemic insult. This was followed by intraperitoneal injections given 24 and 48 hours after the initial insult. Statistically significant histological cytoprotection was demonstrated. Doses of 25 mg/kg appeared to demonstrate significant protection of the cortex (p = 0.0002), the CA1 and CA4 regions of the hippocampus (p = 0.0004 and 0.0001) respectively. At a dose of 50 mg/kg, significant cytoprotection was demonstrated at the hippocampus (CA1 and CA4 regions), in particular at the CA4 region (p = 0.0029). The 100 mg/kg dose appeared to have most significant protection at the CA1 and CA4 regions of the hippocampus (both p = 0.0001), striatum (p = 0.0011), and the thalamus (p = 0.0008). All statistical comparisons were done using non parametric tests (Mann-Whitney U test). Our study demonstrates that baclofen is cytoprotective to ischemic neuronal cells, especially in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783836 TI - Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt. AB - The effects of chronic dietary sodium chloride (NaCl) consumption on renal function and brain dopamine receptors were studied in adult, male normotensive rats. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited significant increases in plasma aldosterone, chloride and changes in urinary electrolyte excretion. In contrast, rats maintained on the high NaCl (8%) diet for 4 weeks demonstrated significant increases in urine volume and urinary sodium, chloride and dopamine excretions and water intake. Rats fed the high NaCl diet displayed a 42-59% decrease (p < 0.001-0.05) in D1 binding in the nucleus accumbens (NA), olfactory tubercle (OT) and the striatum (STM), without any effects on D2 binding in these brain regions. Rats maintained on the low NaCl diet also demonstrated decreased D1 binding in the ventral (24%, p < 0.02) and lateral (29%, p < 0.01) STM, but not in the OT, NA, entopeduncular nucleus and substantia nigra. Rats fed low or high NaCl diets exhibited a 35-180% increase (p < 0.01-0.05) in D2 binding in several mid-brain areas (e.g. hypothalamus, thalamus and hippocampus) and hindbrain regions (e.g. superior colliculus and nucleus tractus solitarius) without affecting the D1 binding. These data indicate that chronic modification of dietary salt intake profoundly affects the renal handling of sodium/water excretion and leads to selective up- and/or down-regulation of DA receptor subtypes in different areas of the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783837 TI - Current Triton X-100 treatments do not allow a complete plasminogen activator extraction from developing nervous tissue. AB - Determinations of plasminogen activator (PA) activity are usually performed in Triton X-100-treated tissue homogenates or crude membrane fractions. Such preparations usually involve a single Triton X-100 treatment. In the present paper we describe the pattern of variability of PA activity measured in different fractions obtained from the developing chick CNS by a repetitive procedure of Triton X-100 treatment and ultracentrifugation. To further characterize this PA activity we have also performed zymographic analyses during the embryonic development and the early postnatal life. Our results show that: a) a single Triton X-100 treatment does not completely extract the enzyme and this lead to an underestimation of the total PA activity; b) the PA activity is associated with the particulate component of the total tissue homogenate requiring its complete solubilization more drastic Triton X-100 treatments; c) better estimations of total and specific activities are obtained by using soluble fractions derived by ultracentrifugation from Triton X-100-treated membrane fractions; d) the developing chick optic lobe expresses only one kind of PA molecule along the entire development; e) the level of PA activity vary characteristically during the ontogeny and the early postnatal life indicating the existence of a developmentally regulated mechanism of PA expression. PMID- 7783838 TI - Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism. AB - The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction. PMID- 7783839 TI - Involvement of both a Zn2+ site and an anionic binding site in the selective inhibition of a Zn(2+)-glycerophosphocholine cholinephosphodiesterase by thiols and tellurites. AB - Inhibition of a Zn(2+)-glycerophosphocholine cholinephosphodiesterase by thiols or tellurites were examined mechanistically. Inactivation of the phosphodiesterase by thio-carboxylates, which was due to the removal of Zn2+ in the catalytic site, was enhanced by introduction of an amino group in the structure of thiols, suggesting the presence of an anionic site adjacent to a Zn2+ site. In support of the suggestion, it was found that thiols, associable with both a Zn2+ site and an anionic site, were more potent reversible inhibitors; dimethylaminoethanethiol (Ki, 17 microM), diethylaminoethanethiol (Ki, 1.2 microM) and thiocholine (Ki, 2.6 microM). Meanwhile, the inhibition of the phosphodiesterase by tellurites is ascribed to the binding of tellurite anions to a Zn2+ site, based on the protective action of tellurite anions against the inactivation of the enzyme by EDTA. Moreover, the inhibition of the phosphodiesterase by tellurites was prevented by phosphate ions, which expressed the protective effect against EDTA inactivation. In further support, it was observed that tellurite and thiocholine appeared to interact with active site in an additive manner, in contrast to a synergistic action between tellurites and quaternary ammonium compounds such as acetylcholine or choline. PMID- 7783841 TI - Inhibition of plasma membrane and mitochondrial transmembrane potentials by ethanol. AB - The actions of ethanol and its primary oxidative metabolite, acetaldehyde, on plasma membrane and mitochondrial transmembrane potentials were examined in rat brain using fluorescence techniques. Subchronic treatment of adult rats with ethanol resulted in a significant depolarization of both the plasma and mitochondrial membranes when the mean blood ethanol level of the rats was 59 +/- 11 mM (mean +/- SEM, n = 6). Acute dosing of animals (4.5 g/kg, i.p.) failed to show any significant alterations. Various concentrations of ethanol, added in vitro to a crude synaptosomal preparation isolated from the rat cerebrocortex (P2) from untreated animals, depolarized both the plasma and mitochondrial transmembrane potentials in a dose-related manner. Addition of acetaldehyde in vitro did not reveal any significant effects on plasma or mitochondrial transmembrane potential. PMID- 7783840 TI - Changes in extracellular levels of glutamate and aspartate in rat substantia nigra induced by dopamine receptor ligands: in vivo microdialysis studies. AB - The microdialysis technique was utilized to study the local effects of D1 and D2 family type dopamine (DA) receptor (R) ligands on the in vivo release of endogenous glutamate (GLU) and aspartate (ASP) from rat substantia nigra (SN). Addition to the dialysis perfusion solution of either D1-R and D2-R agonists, such as SKF-38393 (50 and 100 microM) and Quinpirole (5 and 10 microM), resulted in dose-dependent increases in extracellular concentrations of GLU and ASP, respectively. The SKF-38393 and Quinpirole-induced effects were reduced by SCH 23390 (0.5 microM), a D1-R antagonist, and by Spiperone (1.0 microM), a D2-R antagonist, respectively. However, SCH-23390 and Spiperone did increase GLU and ASP extracellular concentrations. Local infusion with Tetrodotoxin (TTX) (1.0 microM), a blocker of voltage-dependent Na+ channels, increased basal extracellular levels of GLU. In addition, co-infusion of TTX and SKF-38393 evoked increases in extracellular GLU levels higher than those observed after SKF-38393 alone. Finally, chemical lesions of nigral DA cells with 6-OH-DA increased the basal extracellular levels of GLU. It is proposed that the release of GLU and ASP from SN may be regulated by D1- and D2-receptors present in this basal ganglia structure. In addition, part of the D1 receptors present in SN might be located presynaptically on GLU-containing nerve endings. PMID- 7783842 TI - Characterization of the carrier-mediated [3H]GABA release from isolated synaptic plasma membrane vesicles. AB - Synaptic plasma membrane (SPM) vesicles were isolated under conditions which preserve most of their biochemical properties. Therefore, they appeared particularly useful to study the cytoplasmic GABA release mechanism through its neuronal transporter without interference of the exocytotic mechanism. In this work, we utilized SPM vesicles isolated from sheep brain cortex to investigate the process of [3H]GABA release induced by ouabain, veratridine and Na+ substitution by other monovalent cations (K+, Rb+, Li+, and choline). We observed that ouabain is unable to release [3H]GABA previously accumulated in the vesicles and, in our experimental conditions, it does not act as a depolarizing agent. In contrast, synaptic plasma membrane vesicles release [3H]GABA when veratridine is present in the external medium, and this process is sensitive to extravesicular Na+ and it is inhibited by extravesicular Ca2+ (1mM) under conditions which appear to permit its entry. However, veratridine-induced [3H]GABA release does not require membrane depolarization, since this drug does not induce any significant alteration in the membrane potential, which is determined by the magnitude of the ionic gradients artificially imposed to the vesicles. The substitution of Na+ by other monovalent cations promotes [3H]GABA release by altering the Na+ concentration gradient and the membrane potential of SPM vesicles. In the case of choline and Li+, we observed that the fraction of [3H]GABA released relatively to the total amount of neurotransmitter released by K+ or Rb+ is about 28% and 68%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783843 TI - Synaptosomal glutamate uptake in a model of experimental cerebral ischemia. AB - In the present investigation we studied the synaptosomal uptake of glutamate in brain omogenate of Mongolian gerbils submitted to bilateral common carotid occlusion, with and without subsequent return of blood flow. The results show that glutamate uptake after ischemia is reduced by about 35%. The damage appears to be persistent, since return of blood flow restores uptake only slightly. The membrane alterations occurring in ischemia could explain the persistence of glutamate transporter impairment. Besides the blockade of NMDA receptors, the stimulation and/or the protection of the uptake systems for glutamate could be of help in preventing neuronal ischemic damage. PMID- 7783844 TI - Effect of dibutyryl cyclic AMP and dexamethasone on glutamine synthetase gene expression in rat astrocytes in culture. AB - Astrocytes are the primary site of glutamate conversion to glutamine in the brain. We examined the effects of treatment with either dibutyryl cyclic AMP and/or the synthetic glucocorticoid dexamethasone on glutamine synthetase enzyme activity and steady-state mRNA levels in cultured neonatal rat astrocytes. Treatment of cultures with dibutyryl cyclic AMP alone (0.25 mM-1.0 mM) increased glutamine synthetase activity and steady state mRNA levels in a dose-dependent manner. Similarly, treatment with dexamethasone alone (10(-7)-10(-5) M) increased glutamine synthetase mRNA levels and enzyme activity. When astrocytes were treated with both effectors, additive increases in glutamine synthetase activity and mRNA were obtained. However, the additive effects were observed only when the effect of dibutyryl cyclic AMP alone was not maximal. These findings suggest that the actions of these effectors are mediated at the level of mRNA accumulation. The induction of glutamine synthetase mRNA by dibutyryl cyclic AMP was dependent on protein synthesis while the dexamethasone effect was not. Glucocorticoids and cyclic AMP are known to exert their effects on gene expression by different molecular mechanisms. Possible crosstalk between these effector pathways may occur in regulation of astrocyte glutamine synthetase expression. PMID- 7783845 TI - Glutamate efflux from rat brain slices and cultures: a comparison of the depolarizing agents potassium, 4-aminopyridine, and veratrine. AB - The major excitatory amino acid neurotransmitter in the mammalian brain is glutamate (GLU). GLU release from nerve terminals is both calcium-dependent and independent, yet these mechanisms of release are not fully understood. Potassium, 4-aminopyridine (4-AP) and veratrine are commonly used depolarizing agents that were studied for their ability to stimulate GLU efflux from brain slices. These agents produced significant regional variations in GLU efflux from rat brain slices. Potassium was the most potent of the three secretogogues tested. 4-AP produced a significant GLU efflux only in the cerebellum. Veratrine produced consistent stimulation of GLU efflux from all brain regions tested. Potassium was the only depolarizing agent tested that stimulated GLU release from primary astroglial cultures of rat cerebral cortex. All three agents also demonstrated an ability to inhibit GLU reuptake in brain slice preparations. This data suggest that both GLU release and uptake are modulated in a regionally selective manner, and that commonly used depolarizing agents affect not only calcium-dependent neuronal release, but also uptake and glial responses. PMID- 7783846 TI - Acute effects of sigma ligands on the extracellular DOPAC level in rat frontal cortex and striatum. AB - Acute administration of (+)-N-allylnormetazocine ((+)-SKF-10,047) and (+/-) pentazocine, was found to increase the extracellular level of 3,4 dihydroxyphenylacetic acid (DOPAC), a major dopamine (DA) metabolite, in the rat frontal cortex. By contrast, these benzomorphan sigma ligands did not change the extracellular DOPAC level in the rat striatum. On the other hand, 1,3-di(2 tolyl)guanidine (DTG) increased the extracellular DOPAC level in the frontal cortex, while it decreased that level in the striatum. Another non-benzomorphan sigma ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) decreased the extracellular DOPAC level in both frontal cortex and striatum. Moreover, the increase of the extracellular DOPAC level elicited by (+)-SKF 10,047 was significantly inhibited by rimcazole, a putative sigma antagonist, while the DTG-induced increment was not reversed by rimcazole. These findings indicated that the effects of sigma ligands on the mesocortical DA neurons differed from those on the nigrostriatal DA neurons. In addition, the effects of benzomorphan sigma ligands on the central DA neurons were different from those of non-benzomorphan sigma ligands. PMID- 7783848 TI - Neuropeptide Y: distribution of immunoreactivity and quantitative analysis in diencephalic structures and cerebral cortex of dwarf hamsters under different photoperiods. AB - The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was investigated by immunohistochemistry and radioimmunoassay (RIA) in the brain of the Djungarian hamster (Phodopus sungorus) held under either long or short photoperiods. In the diencephalic and telencephalic structures studied, distinct patterns of NPY-LI were basically consistent in male and female animals of both groups. NPY levels detected by RIA from tissue samples taken at six time points throughout the 24-hour cycle were in the range of 15-60 pmol/mg protein in the diencephalon or below 5 pmol/mg protein in cerebral cortex. In the diencephalon, immunoreactive structures were seen in the preoptic, peri- and paraventricular, supraoptic, anterior, lateral, dorso- and ventromedial hypothalamic nuclei and in the median eminence. The suprachiasmatic nuclei exhibited a dense innervation by NPY-LI terminals mainly in its ventrolateral subdivision. NPY levels in the suprachiasmatic nucleus were nocturnally augmented under long-day, but not under short-day conditions. The quantification of NPY in the paraventricular nucleus revealed a decrease at night in long-day animals and a small nocturnal augmentation in short-day hamsters. In the pineal gland and habenular nuclei, varicose fibers were observed which appeared mainly perivascular in location (pineal) or formed a dense plexus (habenular nuclei). Pineal NPY contents fell during the night in long-day animals and were relatively constant in short-day hamsters. NPY-LI structures were also observed in the metathalamic intergeniculate leaflet and in a variety of telencephalic structures including the cerebral cortex, caudate nucleus putamen, lateral septal nucleus, bed nucleus of the stria terminalis and amygdala. PMID- 7783849 TI - Pro-melanin concentrating hormone messenger ribonucleic acid and peptides expression in peripheral tissues of the rat. AB - Melanin-concentrating hormone (MCH) is a cyclic peptide which is predominantly synthetized in the hypothalamus of fish and mammalian brains. In the present paper we examined the expression of MCH mRNA and pro-MCH-derived peptides, i.e. MCH and neuropeptide-(N)-glutamic acid (E) isoleucine (I) amide (NEI), in peripheral tissues of adult rodents. By means of polymerase chain reaction (PCR) of reverse-transcribed RNA, low levels of MCH gene transcripts were detected reliably in testis, stomach, and intestine of Sprague-Dawley and Wistar rats, whereas strong expression was found in hypothalamus. Subsequent sequence analysis of the PCR products verified the authenticity of MCH mRNA found in hypothalamus and stomach. The length of MCH RNA species was measured by Northern blot and multiple MCH RNA species were detected in both rat species. Shortest polyadenylated tails were found in MCH RNAs isolated from the peripheral organs by comparison with hypothalamus MCH RNAs of Wistar rats. In order to localize MCH expression in gastrointestinal and genital tracts of Wistar rats we performed in situ hybridization with specific 33P-labeled oligoprobes joined to immunocytochemical studies with rat MCH or NEI antisera. In testis, the MCH transcripts and pro-MCH-derived peptide immunoreactivities were found at the periphery of the seminiferous tubules, suggesting expression in Sertoli cells. Studies with MCH oligoprobes and antisera directed towards MCH, NEI and alpha A inhibin revealed similar pattern of expression in isolated Sertoli cells from Swiss mice, indicating that MCH RNA species were actually synthesized and translated in these cells. In the gastrointestinal (GI) tract, the cells expressing MCH RNA species and pro-MCH-derived peptides were predominantly expressed in the antral portion of the stomach and duodenum. Strikingly, distinct oligoprobes, recognizing antisense MCH transcript, revealed a pattern of hybridization in the GI tract similar to this observed with oligoprobes revealing the mature MCH mRNA. Furthermore, total RNA from the pyloric junction, duodenum, jejunum, ileum and hypothalamus as well appeared to contain RNA complementary to MCH mRNA suggesting therefore that antisense MCH RNA species may play a general role in regulation of MCH synthesis. Taken together, our present and previous data indicate that authentic MCH RNA species and translational products are expressed in various rodent tissues at the periphery. The cellular location suggests that MCH and associated peptides may play a role in spermatogenesis and in digestive processes. PMID- 7783847 TI - Expression of synapsin I gene in primary cultures of differentiating rat cortical neurons. AB - Synapsin I is a neuron-specific protein which is present in two isoforms, Ia and Ib. In the last few years this protein has been demonstrated to play a central role in the regulation of neurotransmitter release and synaptic plasticity. In this paper the developmental expression of this protein has been investigated in primary neuronal cultures from fetal rat brain cortices. The presence of thyroid hormone in the culture medium stimulates an early expression of the protein without exerting any effect at the level of mRNA transcription and accumulation. These observations implicate a T3-dependent regulation of this neuron-specific gene at the level of mRNA translation. PMID- 7783850 TI - Bombesin-like immunoreactivity in the forebrain and pituitary and regulation of anterior pituitary hormone release by bombesin in goldfish. AB - The presence and distribution of bombesin (BBS)/gastrin-releasing peptide (GRP) like immunoreactivity (IR) was examined in the goldfish pituitary and forebrain. BBS/GRP-like IR nerve fibres were consistently observed throughout the pituitary neurointermediate lobe (NIL); occasionally, BBS/GRP-like material was localized in cells and few fibres within the pars distalis. Within the goldfish forebrain, sparse, fine-beaded BBS/GRP-like IR fibres and few perikarya were detected in the preoptic hypothalamus. BBS/GRP-like IR material was also present in the ventro posterior hypothalamus and the hypothalamic inferior lobes, and, in particular, within the nucleus lateral tuberis pars anterioris (NLTa) and nucleus lateral tuberis pars posterioris (NLTp), nucleus anterior tuberis (NAT), nucleus recessus lateralis (NRL), nucleus recessus posterioris (NRP), and the nucleus diffusus lobi inferioris (NDLI). Several BBS/GRP-like IR perikarya were observed in periventricular regions of the NLT, NRL, and NRP. Finally, BBS/GRP-like IR material was detected in the nucleus habenularis, the nucleus rotundus, several thalamic nuclei, and the optic tectum of the dorso-posterior diencephalon. The presence of BBS/GRP-like IR material within the preoptic hypothalamus, hypophysial stalk, and in the pituitary suggests that BBS-like peptides may regulate pituitary hormone release in fish. Perifusion of goldfish pituitary fragments with initial pulses of 0.1, 10, 100 or 1,000 nM BBS stimulated both growth hormone (GH) and gonadotropin (GtH-II) release. Repeated pulses of the same dose of BBS generally stimulated GH and GtH-II release to a similar magnitude. These studies provide initial evidence that BBS/GRP-like peptides are present within the central nervous system of teleost fish. The anatomical distribution of BBS/GRP-like IR in goldfish hypothalamic feeding center supports our previous report indicating a role for BBS in the central regulation of food intake in fish. Additionally, the presence of BBS/GRP-like IR material in the pituitary and brain areas associated with the regulation of anterior pituitary hormone secretion, as well as evidence demonstrating a direct action of BBS at the level of the goldfish pituitary to modify GH and GtH-II secretion, indicates that BBS/GRP-like peptides likely act to regulate pituitary hormone release in teleosts. PMID- 7783851 TI - Pituitary adenylate cyclase-activating polypeptide activates different signal transducing mechanisms in cultured cerebellar granule cells. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel 38-residue neuropeptide which stimulates adenylate cyclase activity in rat pituitary cells as well as in other neuronal and non-neuronal tissues. In this study we have investigated whether PACAP27 and PACAP38 may stimulate either cyclic AMP accumulation or phosphoinositide formation in cultured cerebellar granule cells. In cultures at 8 days of maturation in vitro (DIV), a 15-min exposure to PACAP27 or PACAP38 equally promoted a concentration-dependent increase in intracellular cAMP content: the effect was significant at 1-5 nM and maximal between 10 and 100 nM, while VIP was 1,000-fold less potent in elevating cAMP levels. In the presence of 3-isobutyl-1-methylxanthine (200 microM), stimulation by PACAP was present already at 0.1 nM and was maximal (6-fold increase) at 1 nM. A rapid elevation in intracellular cAMP (about 80%) was observed within a 30-second exposure to 10 microM PACAP38 or PACAP27; the maximal activity of PACAP was present between 15 and 30 min and progressively declined at 60 min without reaching basal values. PACAP27 and PACAP38, but not VIP, were also able to stimulate inositol phospholipid hydrolysis: PACAP38 (EC50: 0.16 nM) was 10-fold more potent than PACAP27 (EC50: 2.1 nM) in stimulating [3H]inositol phosphate formation. The effect of PACAP was rapid: fractionation of [3H]inositol phosphates revealed that inositol trisphosphate and inositol bisphosphate increased earlier (within 20 s) than inositol monophosphate (within 60 s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783852 TI - Nicotinic agonists administered into the fourth ventricle stimulate norepinephrine secretion in the hypothalamic paraventricular nucleus: an in vivo microdialysis study. AB - Nicotinic cholinergic agonists stimulate ACTH secretion by a central mechanism involving brainstem catecholamines. In vivo microdialysis studies were conducted to measure the release of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) in response to the administration of nicotine (Nic) or another nicotinic cholinergic (NAch) agonist, cytisine (Cyt), directly into the IVth ventricle. Alert, freely mobile rats, equipped 24 h previously with a chronic guide cannula in the IVth ventricle and microdialysis probe in the PVN, were injected with artificial cerebrospinal fluid (CSF, 500 nl/60 s), Nic (1-5 micrograms), or Cyt (1-25 micrograms) after three 20-min baseline samples had been taken. Analysis of the dialysates by HPLC with electrochemical detection demonstrated the dose-dependent secretion of PVN NE to Nic or Cyt with ED50s of approximately 1 or 6 micrograms, respectively; these were completely blocked by prior IVth ventricular injection of the NAch antagonist, mecamylamine (4 micrograms). In contrast, alpha-bungarotoxin, which antagonizes the action of NAch agonists by acting through the alpha 7 bungarotoxin-type NAchR, failed to reduce the NE response to Nic. Partial, but significant desensitization of NE secretion in response to a second injection of Nic (2.5 or 5 micrograms) 100 min after the first was seen, whereas NE responses to the second injection of Cyt (5 or 25 micrograms) were completely desensitized. However, cross-desensitization of each agonist to the other did not occur. This may reflect heterogeneity of the NAch receptor subtypes involved. The results of this study establish a correlation between the action of nicotine on brainstem norepinephrinergic regions and the resultant release of NE in the PVN, which would lead to the release of ACTH secretagogues. PMID- 7783853 TI - Effect of testosterone and its metabolites upon the level of vasopressin messenger ribonucleic acid in the hypothalamus of the hyperosmotically stimulated male rat. AB - We previously reported that gonadal steroids modify the expression of arginine vasopressin (AVP) in the hypothalamus of rats administered 2% sodium chloride solution for 5 days. Gonadectomy prevented, and testosterone (T) replacement restored, enhanced AVP mRNA levels in the supraoptic nucleus (SON) of male rats receiving this hyperosmotic challenge. The present study investigated the effects of the androgenic and estrogenic metabolites of T on hypothalamic AVP mRNA levels in response to chronic hyperosmolality. Gonadectomized male rats receiving 2% NaCl for 5 days and treated with T, dihydrotestosterone (DHT), or DHT+estradiol (E2), but not E2 alone or empty implants, had increased AVP mRNA levels compared to gonadectomized animals receiving tap water. Our results support a role for T and DHT-mediated effects upon the enhanced accumulation of AVP mRNA in the SON of male rats receiving a chronic hyperosmotic challenge. PMID- 7783854 TI - Effect of chronic hyponatremia on central and peripheral oxytocin and vasopressin secretion in rats. AB - Previous studies have shown that many treatments that stimulate the peripheral secretion of oxytocin (OT) and vasopressin (AVP) from the pituitary simultaneously increase the levels of these peptides in the cerebrospinal fluid (CSF). Since osmotically and nonosmotically stimulated pituitary secretion of OT and AVP is markedly blunted in hyponatremic rats, the present studies evaluated whether central OT and AVP secretion into the CSF is similarly inhibited during sustained hyponatremia. Adult male rats with indwelling cisterna magna cannulae were rendered hyponatremic (plasma [Na+] < 110 mmol/l) by s.c. infusion of desmopressin (dDAVP; 10 ng/h) in combination with ingestion of a liquid diet for 3 days, then subjected to osmotic (i.v. or i.p. injection of 2 M NaCl; HS) or nonosmotic (6 mmol/kg of 0.15 M LiCl i.p.) stimulation. In normonatremic rats both i.v. and i.p. HS caused marked increases in plasma OT and AVP levels 30 min after treatment. Significant elevations of OT, but not AVP, were also present in CSF. Despite similar increases in plasma Na+ concentrations, plasma OT responses in the hyponatremic rats were absent after HS i.v. and were significantly blunted after HS i.p., but neither group had increased plasma AVP. In parallel with the plasma results, CSF OT responses were absent in hyponatremic rats given HS i.v. and significantly blunted in hyponatremic rats given HS i.p., but neither group had increased CSF AVP. Nonosmotic stimulation with isotonic LiCl increased OT levels both in plasma and CSF in normonatremic rats 20 min after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783855 TI - Regulation of thyrotropin-releasing hormone in the posterior pituitary. AB - Although the presence of thyrotropin-releasing hormone (TRH) in the posterior pituitary (PP) was reported more than one decade ago, knowledge on its origin, regulation and functional significance is lacking. In the present study we investigated the regulation of TRH in the rat PP. Analysis by specific RIA, anion and cation exchange chromatography and reverse-phase HPLC showed that all TRH immunoreactivity in the PP is accounted for by authentic TRH. Induction of hyperthyroidism with thyroxine increased levels of TRH in the PP by 20%, whereas in methimazole-treated, hypothyroid rats the content decreased by 25% versus untreated, euthyroid controls. Food deprivation for 3 days increased levels by 35% and refeeding completely normalized TRH content again. Also 14-17 days after castration, TRH in the PP was increased by 25% while testosterone substitution prevented this increase. Castration did not affect proTRH mRNA levels in the hypothalamus. One week after adrenalectomy or daily subcutaneous dexamethasone injections, TRH content in the PP was not affected. Treatment with disulfiram, an inhibitor of the peptidylglycine alpha-amidating monooxygenase (PAM), reduced levels of TRH in the PP by 20%. ProTRH and PAM mRNA levels were not affected in the hypothalamus by this treatment. Since TRH in the PP has been suggested to play a role in prolactin (PRL) release, we determined the content of TRH in the PP during a 6-hour suckling stimulus that increased PRL levels in peripheral blood 30-fold. Whereas TRH in the median eminence increased by 35%, 6 h after the initiation of suckling, TRH levels in the PP remained constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783856 TI - Adrenergic control of alpha-melanocyte-stimulating hormone release in frog pituitary is mediated by both beta- and a nonconventional alpha 2-subtype of adrenoreceptors. AB - Previous studies have shown that melanotrope cells of the pars intermedia of Rana ridibunda are inhibited by dopaminergic D2 agonists and stimulated by beta adrenergic agonists. In the present study, we have examined the possible involvement of alpha-adrenoreceptors in the regulation of frog melanotrope cells. Reversed-phase HPLC analysis combined with electrochemical detection revealed the presence of both dopamine and noradrenaline in pars intermedia extracts (74.1 and 3.2 ng/mg protein, respectively), while adrenaline was undetectable. Administration of graded doses of noradrenaline and adrenaline (from 0.1 to 10 microM) to perifused frog neurointermediate lobes induced a dose-dependent inhibition of alpha-MSH release. The inhibitory effect of adrenaline was partially blocked by the D2-dopaminergic antagonist sulpiride and totally suppressed by concomitant administration of sulpiride and yohimbine (an alpha 2 adrenergic antagonist). Conversely, in the presence of sulpiride, noradrenaline provoked a strong stimulation of alpha-MSH secretion which was totally blocked by the beta-adrenergic antagonist propranolol. Taken together, our results indicate that endogenous catecholamines may exert a complex regulatory action on frog melanotrope cells through activation of dopaminergic D2, alpha 2- and beta adrenergic receptors. PMID- 7783857 TI - Direct regulation of hypothalamic corticotropin-releasing-hormone neurons by angiotensin II. AB - The possible role of angiotensin II (AII) in the control of the hypothalamic pituitary-adrenal (HPA) axis was studied in the rat by examining the regulation and cellular localization of AII receptors in the paraventricular nucleus (PVN) of the hypothalamus and the effect of AII on corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNA levels. In situ hybridization studies using cRNA 35S-labelled probes showed that while type 1 AII receptor (AT1) mRNA levels were high in the periventricular and parvicellular pars of the PVN, only very low levels were present in the magnocellular pars. A similar distribution of AT1 receptor binding in the periventricular, parvicellular and magnocellular divisions of the PVN was observed in autoradiographic studies in hypothalamic sections labelled with 125I[Sar1,Ile8]AII. In addition, AII receptor binding was clearly evident in nerve fibers adjacent to the PVN. Double-labelling hybridization using digoxigenin-labelled CRH, VP and oxytocin probes and 35S labelled AT1 receptor cRNA probes showed AT1 receptor mRNA in cells stained for CRH mRNA, but not in VP or oxytocin cells. Four hours after a single intracerebroventricular (i.c.v.) injection of 50 ng AII in conscious rats, CRH mRNA levels in the PVN were increased by 43%, similar to the increases observed following acute stress by intraperitoneal (i.p.) injection of 1.5 M NaCl (76%). On the other hand, while i.p. hypertonic saline injection increased VP mRNA levels by 29% in the PVN and by 32% in the supraoptic nucleus, i.c.v. AII injection had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783858 TI - Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates c-fos mRNA expression in the paraventricular nucleus after stress. AB - Corticotropin-releasing factor (CRF) plays a role in coordinating endocrine, physiological and behavioral responses to stressful stimuli. We have previously reported that centrally administered CRF rapidly induces c-fos mRNA expression in most areas that express c-fos following stress: the limbic structures including the hippocampus, amygdala, septal nucleus and hypothalamic nuclei such as the paraventricular nucleus (PVN), and brainstem nuclei such as Barrington's nucleus and locus ceruleus (LC). These results suggest several candidate structures through which CRF could exert its effects on the central nervous system. The aim of the present study was to explore the role of endogenous CRF in activating these brain regions after stress using a specific CRF receptor antagonist, alpha helical CRF(9-41). One hundred micrograms of alpha-helical CRF or vehicle alone was injected into the right lateral ventricle of rats. Thirty minutes later, they were exposed to restraint stress for 30 min, and the rat brain was then perfused transcardially with 4% paraformaldehyde. Another control group of rats was sacrificed 60 min after intracerebroventricular (ICV) injection of vehicle without restraint. In situ hybridization was performed by hybridizing sections with 35S-labeled c-fos cRNA probes. ICV injection of vehicle alone induced a weak c-fos mRNA expression in the lateral septal nucleus (LSV) and PVN in the rats without restraint, probably due to the mild stress of ICV injection. Restraint stress produced strong c-fos mRNA induction in the PVN, LSV, LC and Barrington's nucleus. However, ICV injection of 100 micrograms alpha-helical CRF significantly decreased c-fos mRNA expression in the PVN without affecting c-fos mRNA induction in the LSV, LC, or Barrington's nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783860 TI - Neuroendocrine correlates of the aging brain in humans. AB - Physiological brain aging is characterized by important biochemical and structural changes and by the unbalance among the different neurotransmitters and neuromodulators. The study of the circadian organization of neuroendocrine functions may be considered a clinically reliable tool to investigate the changes of the CNS and particularly of the limbic-hypothalamic system occurring in aged people. The circadian rhythms of plasma melatonin, ACTH and cortisol and of oral temperature were studied in 16 clinically healthy women aged 66-90 years and in 14 young controls aged 20-30. In addition, the effect of dexamethasone on the plasma cortisol circadian rhythm and the cortisol response to Synacthen pulse intravenous injection were evaluated. All subjects were studied as inpatients, with the same synchronization to the hospital life schedule. When compared with young controls, elderly subjects exhibited a reduction of the mean level and of the amplitude of the circadian rhythm of oral temperature, an increase of the mean level of ACTH and cortisol rhythms and a selective impairment of melatonin nocturnal secretion. Furthermore, elderly subjects showed a reduced sensitivity to the dexamethasone suppression test, by comparison to young controls. These changes were age-related and they may depend either on CNS modification or on alterations of the hormonal metabolic clearance. PMID- 7783859 TI - Ventromedial hypothalamic lesions inhibit corticosteroid feedback regulation of basal ACTH during the trough of the circadian rhythm. AB - We have determined the effects of bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) on activity in the hypothalamo-pituitary-adrenal (HPA) system. Acutely, during the first 5 days, lesions of the anterior-medial VMH caused loss of the diurnal rhythms in food intake and plasma corticosterone (B) levels. Plasma B concentrations were elevated during the time of the normal trough of the basal diurnal rhythm in HPA axis activity and the diurnal rhythm in food intake was abolished, in agreement with the results of others. Consistent with hyperactivity in the HPA axis, lesioned rats had increased adrenal weight, decreased thymus and body weights and decreased plasma transcortin concentrations. To determine how lesions of the VMH provoke these increases in activity of the HPA system, the sensitivity of ACTH in adrenalectomized, lesioned rats to replacement with exogenous B was determined under basal conditions during the trough (morning-AM) and peak (evening-PM) of the diurnal rhythm in HPA axis activity. ACTH in lesioned rats in the AM was insensitive to feedback over the very low range of plasma B of 1-4 micrograms/dl, whereas sham-lesioned controls exhibited the normal, high sensitivity of ACTH to B at this time of day. There was no difference between the sensitivity of ACTH to this low range of B in the PM in VMH- and sham-lesioned rats. Two to 5 weeks after VMH lesions, as found by others, mean daily plasma B levels did not differ from sham-lesioned controls; however, plasma B during the AM was still mildly elevated in these rats. Inhibition of plasma B in the PM by dexamethasone was less effective in lesioned rats. Although HPA system responses to hypoglycemia, corticotropin-releasing factor and ACTH were normal, the lesioned rats exhibited obesity, hyperinsulinemia, hyperglycemia, hypertension and tachycardia, all signs consistent with mild hyperactivity of the PHA axis. Occupancy of type I, high affinity corticosteroid receptors is known to control basal activity of the HPA system during the trough of the diurnal rhythm and to interact with glucocorticoid receptors to affect basal activity during the peak of the diurnal rhythm and during AM stress. We conclude that VMH lesions disrupt transmission of inhibitory signals, mediated by occupancy of type I corticosteroid receptors, that are initiated by a B feed-back site. PMID- 7783861 TI - The use of sumatriptan in patients on monoamine oxidase inhibitors. PMID- 7783862 TI - Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue? AB - We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue. PMID- 7783863 TI - A primary care plan for neurology. PMID- 7783864 TI - Familial progressive subcortical gliosis: presence of prions and linkage to chromosome 17. AB - Progressive subcortical gliosis (PSG) is a sporadic and familial dementing disease characterized pathologically by astrogliosis at the cortex-white matter junction, a feature present in some prion diseases. With immunocytochemical and Western blot analyses, we investigated the presence of deposits of the prion protein (PrP) and of the protease-resistant PrP isoform, the hallmarks of prion diseases, in six affected members of two large kindreds with PSG. The coding region of the PrP gene was sequenced and chromosomal linkage determined. We demonstrated "diffuse" PrP plaques in the cerebral cortex of two subjects from one kindred and protease-resistant PrP fragments in four of the five subjects examined. We found no mutation in the coding region of the PrP gene. Moreover, the disease was linked to chromosome 17 and not to chromosome 20, where the PrP gene resides. The familial form of PSG is the first human genetic disease characterized by the presence of protease-resistant PrP that lacks a mutation in the coding region of the PrP gene. The linkage to chromosome 17 suggests that other genes are involved in the PrP metabolism. Whether the protease-resistant PrP plays a primary or secondary role in the pathogenesis of this form of PSG remains to be determined. PMID- 7783866 TI - Relationship of headache to phase of the menstrual cycle among young women: a daily diary study. AB - We investigated the relationship between headache occurrence and phase of the menstrual cycle in a 4-month daily diary study of 74 women, 22 to 29 years old, residing in Washington County, Maryland. We selected subjects from women reporting a history of migraine symptoms and at least two migraine headache attacks per month in a 1986 to 1987 population-based survey. Data collection was from March 1987 through April 1988. By using detailed headache symptom information collected daily, we classified headaches into four categories: migraine with aura, migraine without aura, tension-type, and all other headaches. Odds ratios were separately estimated for the individual headache types and all types combined during each of three phases of the menstrual cycle. Risk of migraine without aura was significantly elevated during the first 3 days of menstruation (odds ratio, 1.66; 95% confidence interval, 1.21 to 2.26), but headache risk was not significantly increased during the 2 days immediately preceding onset of menstruation or on the estimated day of ovulation (day 14 before the onset of menstruation). Participants reported headaches on 28% of the study days overall, suggesting that onset of menstruation is an independent but not exclusive precipitating factor for headache attacks among young adult women with migraine. Our data show that onset of menstruation only accounts for a small proportion of migraine attacks among young women with frequent episodes of migraine. PMID- 7783865 TI - Clinical and genetic studies of fatal familial insomnia. AB - We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep. PMID- 7783867 TI - Mitral valve prolapse and the risk of stroke after initial cerebral ischemia. AB - Referral-based studies suggest that patients with cerebral ischemia and mitral valve prolapse are prone to recurrent cerebral ischemic events. Our purpose was to determine the risk of subsequent stroke in a population-based group of patients with ischemic stroke or TIA and mitral valve prolapse. From 1975 through 1990, 49 residents of Olmsted County, MN, had an initial ischemic stroke or TIA and echocardiographically diagnosed mitral valve prolapse. Risk of subsequent stroke in this cohort was compared with the age- and sex-adjusted rates of recurrent stroke after initial cerebral ischemia in the Rochester, MN, population. Mean age of the patients was 72 years. Thirty-one (63%) were women. Nine had subsequent stroke (5.5 per 100 person-years). For Rochester patients who had initial ischemic stroke in the period 1975 through 1984, 10.72 recurrent strokes were expected (relative risk, 0.84; 95% confidence limits, 0.38 to 1.59). For Rochester patients with initial ischemic stroke or TIA in the period 1975 through 1979, 12.31 recurrent strokes were expected (relative risk, 0.73; 95% confidence limits, 0.33 to 1.39). There is no evidence of increased subsequent stroke risk among patients with initial episodes of cerebral ischemia and mitral valve prolapse relative to the age- and sex-adjusted recurrent stroke rates in the community. PMID- 7783868 TI - Autosomal dominant migraine with MRI white-matter abnormalities mapping to the CADASIL locus. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant cerebral arteriopathy mapped to chromosome 19 and characterized mainly by recurrent subcortical ischemic strokes and extensive white-matter signal abnormalities (WMAs) on magnetic resonance imaging. Other clinical features include migraine attacks and progressive subcortical dementia. Herein, we describe several members of the same family who suffered migraine attacks, mostly with aura, associated with WMAs, segregating with an autosomal dominant pattern of inheritance. One individual had a progressive subcortical dementia with similar WMAs. Although ischemic stroke, one of the hallmarks of CADASIL, was not present in this family, we hypothesized that the present disorder resulted from an alteration of the CADASIL gene. Genetic linkage analysis, using four chromosome 19 markers spanning the CADASIL locus, supports this hypothesis. PMID- 7783869 TI - Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study. AB - OBJECTIVE: The joint effects of total cholesterol (TC) levels and the APOE genotype in Alzheimer's disease (AD) were evaluated because of previous reports that the APOE locus epsilon 4 allele was associated with both late-onset AD and elevated TC. DESIGN: Logistic regression was used to determine the effects of the APOE genotype, TC, age, and sex on prediction of AD in a community-based study of 206 cases and 276 controls. RESULTS: The relationship of the APOE genotype and AD was dependent on TC, age, and sex. However, current TC level does not fully explain the epsilon 4-Alzheimer's disease association. Affected men with higher TC and age under 80 years had the highest epsilon 4 allele frequencies. The epsilon 4 frequency declined significantly with age. SIGNIFICANCE: A pathologic role of higher TC or cholesterol-based differential survival of epsilon 4 carrying individuals may be involved in the relationship of the epsilon 4 allele with AD. The observed association of the APOE genotype and AD is expected to depend on the age, sex, and TC distributions of a given sample. PMID- 7783870 TI - Trigeminal neuralgia in multiple sclerosis relieved by a prostaglandin E analogue. AB - Trigeminal neuralgia is an uncommon but troublesome symptom of multiple sclerosis that can be refractory to conventional treatments. Misoprostol, a long-acting prostaglandin E1 analogue, relieved pain in six of seven patients who had failed to respond to conventional pharmacologic therapy. PMID- 7783871 TI - X-linked adrenoleukodystrophy presenting as neurologically pure familial spastic paraparesis. AB - The familial spastic paraplegias (FSPs) are heterogeneous neurologic disorders that are known to occur clinically as "pure" or "complicated" forms. Although some of the complicated FSPs have been linked to specific metabolic defects, the pure forms of this disorder remain idiopathic and are considered to be primary system degenerations. We report the case of a 28-year-old man who has evidenced a neurologically pure spastic paraparesis since age twenty-five. Consistent with this diagnosis were the findings of magnetic resonance imaging, which revealed atrophy of the thoracic spinal cord without evidence for white matter disease in the cerebrum, cerebellum, or brainstem. His 32-year-old brother has also evidenced progressive spastic paraparesis since age 30, but his case is confounded by a severe head injury at age 24 that caused a skull fracture and a focal demyelinating lesion of the right frontal lobe. Both patients have had hypogonadism, requiring treatment with testosterone, since age 20. Measurement of plasma levels of very long-chain fatty acids (VLCFA) revealed that both brothers had concentrations diagnostic of adrenoleukodystrophy; their mother had plasma VLCFA levels in the heterozygous range. We conclude that neurologically pure FSP can be an early manifestation of adrenoleukodystrophy and that levels of plasma VLCFA should be determined for all cases of FSP in which X-linked inheritance appears tenable. These considerations may have bearing on the ongoing linkage studies for these disorders. PMID- 7783872 TI - Extensive macrogyri or no visible gyri: distinct clinical, electroencephalographic, and genetic features according to different imaging patterns. AB - We studied 43 children with extensive brain gyral anomalies diagnosed radiologically and defined by (a) the absence or paucity of sulci over cortical areas affecting at least two lobes in each hemisphere, and (b) the absence or reduction of interdigitation between gray and white matter. We correlated the clinical, EEG, and genetic findings with the imaging features. A seemingly homogeneous group of patients (group A, n = 30) presented a common imaging pattern characterized by four features: (1) a thickened neocortex, (2) widened lateral ventricles, (3) apparent verticalization and widening of sylvian fissures, and (4) bilateral and symmetric distribution of the abnormalities. Another group of patients (group B, n = 13) exhibited heterogeneous imaging anomalies, termed "nonlissencephalic brain malformation," differing in at least one of the following four ways from the radiologic criteria defining group A: absence of verticalization of sylvian fissures (n = 12), thin neocortex (n = 2), normal-size lateral ventricles (n = 2), and asymmetric brain defects (n = 3). In group A, some clinical features had a significantly lower frequency (p < or = 0.01) than in group B: microcephaly, a complete lack of postural development, and intractable epilepsy. There was a significant relationship, but only in group A, between the degree of gyral anomalies and the extent of neurodevelopmental delay. Some EEG patterns (rapid rhythms and delta-theta rhythms) were highly specific for the group A patients. There was lower risk of familial recurrence in group A (recurrence of convolutional anomalies was 3.5% of sibship in group A versus 44% of sibship in group B, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783873 TI - Lacrimation induced by thermal stress in patients with a facial nerve lesion. AB - I measured facial sweating, flushing, and lacrimation during body heating in 10 patients with a facial nerve lesion compromising parasympathetic outflow. During heating, moisture accumulated in the symptomatic eye of patients with facial nerve palsy, particularly in patients with a long-standing lesion. Sweating and flushing in the forehead were symmetrical. These findings suggest that sympathetic neural discharge during heat stress influences lacrimation in the symptomatic eye of patients with a long-standing facial nerve lesion. Cross innervation of lacrimal neurons by sympathetic fibers passing through the sphenopalatine ganglion or occupation of degenerated parasympathetic pathways by sympathetic fibers in the periphery could mediate this response. PMID- 7783874 TI - Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects. AB - We determined the normal limits for various neuropathic tests in healthy subjects. The study, the Rochester Diabetic Neuropathy Study (RDNS), is noteworthy because of its size (more than 400 subjects), random selection of subjects, and selection of at least 15 men and 15 women without neuropathy, neurologic disease, or diseases predisposing to neuropathy from each hemidecade between 18 and 74 years of age from the population of a defined region (Rochester, MN). Subjects were classified into those with (nonhealthy subjects, RDNS-NS) and without (healthy subjects, RDNS-HS) neuropathy, neurologic or psychiatric disease, or diseases known to predispose to neuropathy. The study provides normal limits for tests used in the RDNS but it has broader uses as well. We found that (1) less than 10% of subjects in the third decade, approximately 20% in the fourth decade, and approximately 30% in the fifth or older decades were placed into the RDNS-NS category; (2) healthy subjects (RDNS HS) retain their ability to walk on toes and heels regardless of age, excessive weight, or lack of physical fitness, but not their ability to arise from a kneeled position--lost in more than 5% of persons 60 years and older; (3) the frequency of decreased or absent ankle reflexes exceeds 5% in healthy subjects older than 50 years--limiting their value as a sign of diabetic polyneuropathy and necessitating a grading change with age in the neuropathy impairment score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783875 TI - Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. AB - MRI has provided insight into the pathophysiology and course of MS, particularly through the use of a paramagnetic contrast agent that allows visualization of blood-brain barrier (BBB) breakdown. Neither the overall frequency of BBB breakdown in MS patients nor the characteristics associated with BBB breakdown in MS are known. We studied 68 relapsing-remitting MS (RRMS) patients with three monthly MRIs to examine these questions. Seventy-eight percent of the RRMS patients studied had evidence of BBB breakdown on at least one MRI. While there was a great deal of variability among patients in terms of mean enhancing lesion frequency, BBB breakdown was associated with younger age at onset of disease, measured by age at first symptom or age at diagnosis, and more severe disease as measured by Expanded Disability Status Scale scores equal to or greater than 4.0. We found no relationship between BBB breakdown and duration of disease or gender. We conclude that BBB breakdown is a relatively common phenomenon in RRMS patients and may be most commonly found in patients with more aggressive disease and younger onset. These findings have implications for clinical trials that use MRI as an outcome measure. PMID- 7783876 TI - Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients. AB - We present two patients with Gerstmann-Straussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129. PMID- 7783878 TI - Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. AB - Elevated iron levels in the substantia nigra (SN) of the brain in Parkinson's disease (PD) may mediate lipid peroxidative reactions, promoting SN neuronal death. To assess SN iron accumulation in living PD patients and its relation to motor performance, we measured, in 13 nondemented PD patients and 10 normal control subjects, simple reaction time (SRT) and simple movement time (SMT), followed by head MRI in a 3-tesla system. We measured T2 and T2* in the right and left SN of all subjects and calculated R2', the relaxation rate due to local magnetic field in-homogeneities, from these values. Asymmetries of 1/T2 (R2), 1/T2* (R2*), or R2' versus asymmetries of SRT and SMT were assessed in eight PD subjects who had not taken anti-PD medication(s) for 12 hours. The average of right and left SN values for R2 was lower, and R2* and R2' were higher, in PD patients than in controls (R2, p = 0.046; R2*, p = 0.001; R2', p < 0.001). R2' best predicted group differences. The asymmetry of SRT performance was highly correlated with asymmetries of SN R2* (0.91; p = 0.001) and R2' (0.72; p = 0.03). These results strongly suggest that the increases in iron levels seen postmortem in the SN in PD are reflected in increased iron-related MRI contrast at 3 tesla in living PD patients. Correlations with motor performance in PD suggest that the clinical severity of PD may be related to SN iron accumulation. PMID- 7783877 TI - Serum neuron-specific enolase in human status epilepticus. AB - Neuron-specific enolase (NSE) is a sensitive marker of brain injury after stroke, global ischemia, and coma. We report changes in serum NSE (s-NSE) in 19 patients who sustained status epilepticus. s-NSE peaked within 24 to 48 hours after status epilepticus. The mean peak s-NSE level for the entire group was elevated compared with the levels for normal controls (24.87 ng/ml versus 5.36 ng/ml, p = 0.0001) and for epileptic controls (24.87 ng/ml versus 4.61 ng/ml, p = 0.0001). The mean peak s-NSE level for the 11 subjects without an acute neurologic insult (15.44 ng/ml) was also significantly increased compared with levels for normal and epileptic controls. Further, s-NSE was significantly correlated with outcome and duration. We conclude that s-NSE is a promising in vivo marker of brain injury in status epilepticus and warrants further study in larger populations. PMID- 7783879 TI - Visual alterations in de novo Parkinson's disease: pattern electroretinogram latencies are more delayed and more reversible by levodopa than are visual evoked potentials. AB - There are increased latencies of pattern-reversal visual evoked potentials (VEPs) and electroretinograms (PERGs) in Parkinson's disease (PD) patients who have not received therapy. This study aimed to evaluate whether these delays are present in the early stage of PD and whether they are dopamine-sensitive. The results show that both PERG P50 and VEP P100 latencies are increased (p < 0.0001) in a group of patients with de novo PD (13 subjects; 13.3 +/- 5.6 months' mean disease duration) before therapy in comparison with an age-matched control group (eight subjects). A larger latency increase (9.9% at the 47% contrast level and 7.8% at the 96% contrast level) was present in PERG recordings than in VEPs (6.2% at the 47% contrast level and 3.9% at the 96% contrast level). Levodopa therapy produced recovery of both PERG and VEP latency increases at both contrast levels, but only the PERG recovery at 47% of contrast was statistically significant. Before therapy, five eyes from PD patients showed no reproducible PERG at the 47% contrast level although the simultaneously recorded VEP was present. Both potentials were recordable in the same eyes at the 96% contrast level. During therapy, four of those five eyes showed a clear PERG even at the 47% contrast level. We conclude that, using an adequate midspatial frequency, both VEPs and PERGs are delayed even in the early stage of PD, and that PERGs are more sensitive if low contrast (47%) is used. The larger alterations, as well as the larger recovery during levodopa therapy, seem to correlate the PERG response more than the VEP response to dopaminergic transmission. PMID- 7783880 TI - GM1 ganglioside treatment of Parkinson's disease: an open pilot study of safety and efficacy. AB - We performed an open-label study testing the effects of GM1 ganglioside on 10 Parkinson's disease (PD) patients. Patients received 1,000 mg of GM1 by IV infusion after the last of three baseline functional assessments. Patients then self-administered GM1 at a dose of 200 mg/d, by subcutaneous injection, for 18 weeks. Under these conditions, GM1 ganglioside proved to be safe and well tolerated. There were no serious adverse events and none of the patients developed elevated anti-GM1 antibody titers. Improvements on at least some functional measures were present in most patients, beginning after 4 to 8 weeks of GM1 treatment. When functional improvements occurred, they lasted for the duration of the study. These results suggest that GM1 ganglioside is well tolerated and may be a useful adjunct to the treatment of PD, and that a double blind, placebo-controlled study is now warranted. PMID- 7783882 TI - Ictus emeticus: further evidence of nondominant temporal involvement. AB - We report two cases of ictal vomiting in patients who had left temporal lobe epilepsy. In one patient, vomiting developed when the discharge spread to the right temporal lobe as seen during depth electrode recording. In the second patient, ictal vomiting occurred with a restricted left temporal discharge, but the patient was left-handed and had right-hemisphere language dominance. These cases provide additional evidence of the involvement of the nondominant temporal lobe in ictus emeticus. PMID- 7783881 TI - Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy. AB - We determined serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 children with epilepsy who had been receiving carbamazepine (58 children), phenobarbital (22 children), or valproic acid (39 children) for 7 months to 10.5 years (mean, 5.8 years). None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant for all except LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TG level differ significantly from the corresponding control-group mean. Our results suggest, in contrast to previous reports, that the effects on the serum lipid profile of long term treatment with hepatic-enzyme-inducing antiepileptic drugs (such as carbamazepine and phenobarbital) are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in children with epilepsy receiving carbamazepine or phenobarbital. PMID- 7783883 TI - Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. AB - We followed 828 nondemented residents of Hisayama Town, Kyushu, Japan, aged 65 years or older (88.3% of the elderly population) for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general Japanese population. Only two subjects were lost to the follow-up, during which period 103 subjects developed dementia. Morphologic examination of the brains of 89 subjects (86.4%) was made by autopsy or CT. We made the initial diagnosis of dementia based on the DSM-III-R criteria, with the diagnoses of vascular dementia (VD) being based on the NINDS-AIREN criteria and Alzheimer's disease (AD) on the NINCDS-ADRDA criteria. The incidence of VD and AD increased with age for both sexes. The age-adjusted total incidence (per 1,000 person years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates for VD were 12.2 for men and 9.0 for women, and for AD, 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology we examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant independent risk factors for the occurrence of VD. In contrast, age and a low score on Hasegawa's dementia scale were significant risk factors for AD, and physical activity was a significant preventive factor for AD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783884 TI - Using motion perimetry to detect visual field defects in patients with idiopathic intracranial hypertension: a comparison with conventional automated perimetry. AB - Motion perimetry, a method of visual field testing that uses computer graphics to measure motion perception, quantitates a subject's ability to detect a coherent shift in position of dots in a defined circular area against a background of fixed dots. Motion size threshold is defined as the smallest detectable circular target in which dot motion is detected. Subjects respond by touching a computer monitor screen with a light pen, first when they see a target (reaction time) and a second time where motion targets are detected (localization). Reaction time (msec) to the stimulus and localization error (number of pixels from target center) are then calculated and stored. We tested on eye in each of 20 idiopathic intracranial hypertension (IIH) patients and 40 age-matched normal subjects by conventional automated perimetry (Humphrey visual field analyzer, program 24-2) and motion perimetry. Pointwise probability plots of individual abnormal test points for size threshold responses were generated for the IIH patients based on the 95% confidence limits of the normal subject responses. An analysis of the subjects' visual field pairs (motion versus conventional automated perimetry) was performed based on these probability plots. The IIH patients had an elevated mean motion threshold (p < 0.001) and reaction time (p < 0.001) compared with the normal subjects. There were no significant differences for the localization errors. Based on the probability plot analysis, there was good correlation of the visual field defects between the two perimetry tests. In addition, motion perimetry identified nerve fiber bundle-shaped defects in nine patients in whom they were not detected with conventional automated perimetry. PMID- 7783885 TI - Cerebral morphometric abnormalities in Tourette's syndrome: a quantitative MRI study of monozygotic twins. AB - Although the pathologic substrate of Tourette's syndrome (TS) is unknown, studies have implicated subtle changes in the basal ganglia. To further investigate structural basal ganglia pathology in TS, we performed morphometric analyses of MRIs of 10 monozygotic twin pairs discordant for severity of TS but concordant for the presence of tic disorders (mean age, 16.3 years; range, 9 to 31 years). Right caudate volume was slightly but significantly reduced in the relatively more severely affected twins as a group compared with the less affected twins (mean difference = 6%, p < 0.01). Most of this difference was attributable to volume reduction in the anterior right caudate (p < 0.02), which was smaller in the more severely affected twin in nine of 10 twin sets. The mean volume of the left lateral ventricle was 16% smaller in the more severely affected twins than in the less severely affected twins (p < 0.01). The normal asymmetry of the lateral ventricles (left greater than right) was not present in the more severely affected twins, who had a trend toward a larger right lateral ventricle. Moreover, the difference within a pair in the degree of loss of the normal ventricular asymmetry correlated with the difference within a pair in the severity of the tic disorder (r = 0.75, p < 0.02). There were no other basal ganglia, ventricular volumetric, or asymmetry abnormalities. These findings partially replicate other MRI studies and suggest that subtle structural abnormalities in the CNS, particularly in the caudate, may play a role in the pathophysiology of TS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7783886 TI - Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability. AB - OBJECTIVE: The use of an efficient noninvasive method to investigate the autonomic nervous system and cardiovascular control during sleep. BACKGROUND: Beat-to-beat heart rate variability displays two main components: a low-frequency (LF) one representing sympathetic and parasympathetic influence and a high frequency (HF) component of parasympathetic origin. Sympathovagal balance can be defined as LF/HF ratio. METHODS/DESIGN: We reviewed normal, standardly staged all night polysomnograms from 10 healthy children aged 6 to 17 years. Recorded 256 second traces of heart rate and respiration were sampled. Power spectra of instantaneous heart rate and respiration were computed using a fast Fourier transform method. RESULTS: The study revealed a decrease in LF during sleep, with minimal values during non-REM slow-wave sleep and elevated levels similar to those of wakefulness during REM. HF increased with sleep onset, reaching maximal values during slow-wave sleep, and behaved as a mirror image of LF. LF/HF ratio displayed changes similar to those in LF. CONCLUSION: The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges toward mean awake levels during REM sleep. The autonomic balance is shifted toward parasympathetic predominance during slow wave sleep. This noninvasive method used to outline autonomic activity achieves results that are in complete agreement with those obtained with direct invasive tools. PMID- 7783887 TI - Demyelinating polyneuropathy in a patient with the tRNA(Leu)(UUR) mutation at base pair 3243 of the mitochondrial DNA. AB - A novel feature of demyelinating polyneuropathy was observed in a patient with the tRNA(Leu(UUR)) mutation at base pair 3243 of the mitochondrial DNA. Based on electrodiagnostic examination, the polyneuropathy was defined as being of the demyelinating, mixed (motor more than sensory) type. In a 1-year follow-up we observed approximately 7% reduction in both the motor and sensory conduction velocities. The other clinical features of the proband included a mild to moderate cognitive impairment and a combined hearing loss with a moderate sensorineural component. The proportion of the mutant genome found in the muscle of the proband was 29%, but the mutation was not found in his blood. A wide variability of the clinical phenotype was observed in the family of the proband. Heteroplasmic mutation was detected in the blood of most family members. The proportion of abnormal mitochondrial DNA was highest in the proband's brother, who had clinically definite mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, while the mutant genome was less frequent or absent in the subjects with less severe phenotypes and in healthy individuals. The findings on this pedigree emphasize the need for studies of complete families in the search for new clinical phenotypes of mutations in mitochondrial DNA. PMID- 7783888 TI - Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders. AB - We performed a short-term, double-blind, placebo-controlled, crossover trial of sodium dichloroacetate (DCA) therapy in 11 patients affected by various primary mitochondrial disorders. Independent measures of oxidative metabolism (venous blood metabolites, exercise testing, phosphorus magnetic resonance [MR] spectroscopy of muscle, and proton MR spectroscopy of brain) were used in order to monitor metabolic responses to the drug. One week of DCA treatment produced significant decreases (p < 0.05) in blood lactate, pyruvate, and alanine at rest and after bicycle exercise. Proton MR spectra collected from a supraventricular volume of interest in brain of seven of 11 patients also showed significant changes. Brain lactate/creatine ratio decreased by 42% during DCA treatment (p < 0.05). Brain choline/creatine ratio (which is low in patients with myelinopathies) increased by 18% (p < 0.01) after therapy. N Acetylaspartate/creatine ratio (an index of neuronal damage or loss) increased by 8% after treatment (p < 0.05). Proton MR spectra collected in two of 11 patients from a volume of interest including the basal ganglia showed similar results (decrease of 36.6% in lactate/creatine; increases of 16% in choline/creatine and 4.5% in N-acetylaspartate/creatine). Phosphorus MR spectroscopy of muscle and self-assessed clinical disability were unchanged. Our study indicates that short term DCA treatment not only lowers blood lactate but also improves indices of both brain oxidative metabolism and neuronal and glial density or function. PMID- 7783889 TI - MRI and PET studies of manganese-intoxicated monkeys. AB - Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa. PMID- 7783890 TI - Frontal lobe neglect in monkeys. AB - Using a crossed-response task, monkeys with neglect induced by frontal lesions appear to have motor rather than sensory neglect. However, the crossed-response task may not reveal sensory neglect (inattention) if no perceptual discrimination is required. We therefore trained two monkeys in a perceptually complex crossed response task. Following unilateral frontal (arcuate gyrus) ablation, we found no contralateral perceptual disorders or sensory neglect in either monkey but did find a failure to respond with the contralateral arm (motor neglect) in both monkeys. We also found that the monkeys made more incorrect responses with the arm ipsilateral to the lesion than they did with the contralateral arm. The errors made by the ipsilateral arm could be a compensatory strategy or a disinhibition phenomenon. Because these incorrect responses were not rewarded and became more frequent as motor neglect improved, the incorrect responses of the ipsilateral arm are not a compensatory strategy, but rather a defect we term "disinhibition hyperkinesia" or "allokinesia." PMID- 7783891 TI - Cardiac arrest following use of sumatriptan. AB - I report a 35-year-old woman with occult coronary artery disease who experienced cardiac arrest within minutes after receiving a first-time dose of subcutaneous sumatriptan for migraine. The patient was resuscitated, and subsequent serial cardiac enzymes indicated myocardial infarction. Because sumatriptan can cause coronary artery vasospasm, patients with significant risk factors for coronary artery disease should be carefully evaluated for cardiovascular disease prior to the use of sumatriptan. PMID- 7783892 TI - Neurologic complications following chiropractic manipulation: a survey of California neurologists. AB - To obtain an estimate of how often practicing neurologists in California encounter unexpected strokes, myelopathies, or radiculopathies following chiropractic manipulation, we surveyed each member of the American Academy of Neurology in California and inquired about the number of patients evaluated over the preceding 2 years who suffered a neurologic complication within 24 hours of chiropractic manipulation. Four hundred eighty-six neurologists were surveyed, 177 responded; 55 strokes, 16 myelopathies, and 30 radiculopathies were reported. Patients were between the ages of 21 and 60, and the majority experienced complications following cervical manipulation. Most of the patients continued to have persistent neurologic deficits 3 months after the onset, and about one-half had marked or severe deficits. Nearly all of the strokes involved the posterior circulation and almost one-half were angiographically proven. Patients, physicians, and chiropractors should be aware of the risk of neurologic complications associated with chiropractic manipulation. PMID- 7783893 TI - Gabapentin treatment of seizures in acute intermittent porphyria. AB - Most antiepileptic drugs (AEDs) available have demonstrated porphyrogenicity in hepatic porphyrias. Gabapentin is a new AED not appreciably metabolized by the liver in humans. We report two patients with acute intermittent porphyria successfully treated with gabapentin without its inducing porphyric crisis. PMID- 7783895 TI - Unique presentation of a prolapsed thoracic disk: Lhermitte's symptom in a golf player. AB - We describe a man with a thoracic disk prolapse whose major manifestation for 10 years was Lhermitte's symptom precipitated by a rotatory movement of the thoracic spine during during the golf swing. PMID- 7783894 TI - Impaired perception of facial identity and facial affect in Huntington's disease. AB - We tested five patients with Huntington's disease on tasks of facial discrimination and facial affect discrimination and matching. Four patients were impaired on a task or tasks of face discrimination, and all patients were impaired on at least one task of facial affect discrimination. We suggest that these findings reflect the role of the basal ganglia or its connections in visual processing. PMID- 7783896 TI - Monozygotic twins discordant for familial hemiplegic migraine. PMID- 7783897 TI - C-5 radiculopathy as a manifestation of giant cell arteritis. PMID- 7783898 TI - Combined system disease after nitrous oxide anesthesia: a case report. PMID- 7783899 TI - Microangiopathy of the brain and retina (Susac's syndrome): two patients with atypical features. PMID- 7783900 TI - Paraneoplastic cerebellar degeneration with anti-Yo antibody in a man. PMID- 7783901 TI - Early American neurologic textbooks. AB - Although European treatises were translated and available to American doctors interested in neurology during the 19th century, the early American neurologic textbooks were distinctive in their comprehensive integration of basic and clinical science. William A. Hammond, in 1871, published the first comprehensive American textbook of neurology, preceding the manuals by Gowers (1886) and Oppenheim (1894) by more than a decade. Four other American adult neurologic textbooks expanded on Hammond's model and incorporated other important topics, including neurologic anatomy, the formal examination, neurochemistry, and complete bibliographies. Bernard Sachs' 1895 textbook was the first pediatric neurologic textbook published in America and made significant contributions to the organization of childhood neurologic disorders. These works functioned as centralized resources for neurologic information, were influential educational tools, and helped foster a growing appreciation of the American neurologic school both nationally and internationally. PMID- 7783902 TI - CNS lymphoma. PMID- 7783903 TI - Beethoven's illness. PMID- 7783904 TI - Reflex sympathetic dystrophy. PMID- 7783905 TI - Meningeal metastases. PMID- 7783906 TI - Rasmussen's syndrome. PMID- 7783907 TI - Cytokine networks in multiple sclerosis. Proceedings of the 3rd Multiple Sclerosis Forum Workshop. Amsterdam, October 22, 1994. PMID- 7783908 TI - Circulating adhesion molecules and inflammatory mediators in demyelination: a review. AB - Accumulating evidence shows that adhesion molecules are critically involved in inflammatory demyelination in the focusing of systemic immune responses into the target tissue, the nervous system. Adhesion molecules are upregulated through the action of cytokines. Tumor necrosis factor alpha appears to be of prime importance. Circulating adhesion molecules probably reflect acute inflammatory episodes in the central and peripheral nervous system, but may also function to modulate ongoing inflammatory responses. Cytokines released by TH1 cells render resident and immigrant macrophages, as well as microglia, activated to synthesize and release increased amounts of inflammatory mediators, such as oxygen radicals, nitric oxide metabolites, and components of the complement system. A more detailed understanding of the sequence of immunopathologic events that culminate in myelin damage in the central and peripheral nervous systems has revealed several sites to which more specific and effective immunointervention can be targeted. PMID- 7783909 TI - The role of autoimmune T lymphocytes in the pathogenesis of multiple sclerosis. AB - Autoimmune T cells play a key role as regulators and effectors of autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components or other locally expressed autoantigens enter the CNS and recognize their antigen(s) on local antigen-presenting cells. After local stimulation, the T cells produce a plethora of cytokines and inflammatory mediators that have profound effects on the local cellular environment, induce and recruit additional inflammatory cells, and contribute to myelin damage. An increasingly detailed knowledge of these processes will greatly facilitate the development of new immunotherapies. This article focuses on the role of T cells in MS. We provide a brief overview of the principles of T-cell immunology, discuss the experimental techniques available for studying T cells, address the role of T cells in the pathogenesis of MS, and highlight modern concepts for immunotherapy. PMID- 7783911 TI - Differential aspects of cytokines in the immunopathology of multiple sclerosis. PMID- 7783910 TI - Inhibitory cytokines and cytokine inhibitors. AB - Cytokines such as interleukin-1 and tumor necrosis factor are involved in the triggering of the immune response, induction of acute inflammatory events, and transition to, or persistence of, chronic inflammation. The action of proinflammatory cytokines is regulated by their receptor expression, downregulation and shedding, by specific inhibitors, and by inhibitory cytokines mainly produced by lymphocytes. This review aims to pinpoint recent findings in the assessment of the biologic activities of cytokine inhibitors and inhibitory cytokines. The suitability of these agents as therapeutic tools is discussed. PMID- 7783913 TI - Interferons in multiple sclerosis: warnings from experiences. AB - Administering or neutralizing a single cytokine is currently considered to represent a promising approach to therapeutic intervention in the immune network in autoimmune diseases. In this article, evidence from animal model experiments is reviewed: intervention in such models can have results opposite to those in the clinical disease; and intended neutralization of a cytokine by the administration of anticytokine antibodies can enhance as well as block in vivo cytokine activity. In experimental autoimmune encephalitis in mice, a model system for multiple sclerosis, administration of interferon gamma (IFN-gamma) was found to reduce disease severity and, concordantly, administration of anti-IFN gamma antibodies was found to aggravate disease. These experimental data are, however, in sharp contrast to the reports on clinical trials, in which IFN-gamma administration was followed by disease relapses. Administration of a neutralizing anti-interleukin-6 (IL-6) antibody to mice to block in vivo activity of IL-6 resulted in increased rather than decreased serum titers, an effect that was found to be due to formation of immune complexes whose elimination from the body is retarded. PMID- 7783912 TI - Experimental autoimmune encephalomyelitis: immunotherapy with anti-tumor necrosis factor antibodies and soluble tumor necrosis factor receptors. AB - Multiple sclerosis (MS) is a demyelinating disease in which an inflammatory cell infiltrate represents a characteristic pathologic feature of active lesions within the CNS. The possibility has been raised that cell-mediated immune mechanisms orchestrate the pathogenesis of MS. Cytokines play a particularly important role in cellular immune mechanisms. These soluble glycoproteins, nonimmunoglobulin in nature, act nonenzymatically to regulate immune cell function. A unique family of cytokines, the tumor necrosis factors (TNFs), demonstrate immunoregulatory activity but are also involved in the effector arm of cellular immune responses. Recently, studies both in vitro and in vivo have suggested a role for TNFs in the pathology of MS. This report summarizes data implicating TNFs in the mechanisms of MS and attempts to apply the anti-TNF approach in the future therapeutic strategy for this disease. PMID- 7783914 TI - The role of cytokines in multiple sclerosis. PMID- 7783915 TI - Cytokine production in the central nervous system. AB - Cytokines participate in normal physiologic events within the CNS. At times of infection and inflammation, their role is emphasized by the upregulation of cytokines and their receptors within the CNS, with concomitant effects on brain function. Cytokines produced by glial cells, T cells, and macrophages interact within the CNS to determine the outcome of the inflammatory reaction. Cytokines have been implicated in the pathogenesis of many CNS diseases, including multiple sclerosis (MS), and their role continues to be intensely investigated. The possibility of novel cytokine therapies, such as anticytokine antibodies or receptor antagonists acting on the cytokine network, provides an optimistic future for treatment of MS and other CNS diseases in which cytokines have been implicated. PMID- 7783916 TI - Suicides in the military: 1980-1992. AB - Data abstracted from the Report of Casualty (DD 1300) is used to describe suicides of active duty personnel for the period 1980 through 1992. The Marine Corps had the fewest suicides (345), but the highest rate (13.65 per 100,000) compared to the other services: Army (1,205/12.38), Air Force (828/11.31), and the Navy (800/11.01). Personnel 17 to 24 years of age accounted for 48% of the suicides and had the highest age group-specific rate, 12.34. White males accounted for 79% of all suicides and had the highest rates across all age groups. Males had significantly higher rates than females in the Air Force, Army, and Navy. The risk of suicide among all active duty males was over two times that of all active duty females and about half that of males in the general population. Active duty females had a risk slightly lower than females in the total population. Enlisted personnel had rates two times higher than officers. Firearms were used in 61% of the male and 55% of the female suicides. PMID- 7783917 TI - Homicide victims in the military: 1980-1992. AB - Data abstracted from the Report of Casualty (DD 1300) is used to describe active duty homicide victims for the period 1980 through 1992. The Marine Corps experienced the fewest homicides (186) but the highest rate (7.36 per 100,000) compared to the other services: Army (619/6.36), Navy (381/5.24), and Air Force (194/2.65). Those younger than 25 accounted for 57% of the homicides and had a higher rate than the older age groups. Blacks had a rate 2.1 times higher than whites, and the overall female-to-male rate ratio was 1.2. Firearms were used against 63% of male and 35% of female homicide victims. Twenty-eight percent of female victims were beaten or strangled and females were over 10 times more likely than males to be strangled. The risk for homicide among active duty males was less than for males in the general population. Conversely, active duty females were at an increased risk for homicide in comparison to both males in the military and females in the general population. PMID- 7783918 TI - Female dentists in the U.S. Army: the origins. AB - Female dentists were not accepted into the U.S. Army Dental Corps until the exigencies of the Korean War in 1951 called for the "maximum utilization" of the country's professional resources. As early as 1898, during the Spanish-American War, and in 1917, during World War I, women dentists had volunteered their services to Uncle Sam. It is appropriate that the story of these early pioneers be told. PMID- 7783919 TI - Organization and work of the War Hospital in Sturba near the town of Livno, Bosnia and Herzegovina. AB - The work of the Croatian Defense Council (armed forces of the Croatian citizens of Bosnia and Herzegovina) War Hospital at Sturba, outskirts of the town of Livno, is described. The hospital was established in the beginning of April and worked until September 1992. It provided services for the battlefield of approximately 100 km of a very difficult mountainous terrain. The hospital was situated in a concrete dugout taken from the Yugoslav Federal Army. It was well equipped and supplied exclusively by numerous donations. Medical personnel were recruited partly from local medical professionals and partly from volunteers from Croatia. During the 5-month period, 597 patients (571 soldiers and 26 civilians) were admitted. A total of 314 operations, 141 in general and 173 in regional anesthesia, were performed. None of the patients died in the hospital. There was not a single epidemic either among soldiers or civilians in the area. PMID- 7783920 TI - Reconstructive surgery during Operations Just Cause and Desert Storm. AB - Operations Just Cause and Desert Storm were of relatively brief duration; however, severe wounds were produced that required complex reconstructive procedures. This paper describes the type of wounds managed in theater and subsequently at three U.S. military medical centers. Specific reconstructive techniques included local and free muscle, fasciocutaneous, and composite flaps. Emphasis is placed on the application of microsurgical techniques to battle related injuries. PMID- 7783921 TI - Health behaviors of military retirees: incidence of smoking and alcohol use. AB - Previous investigations of the health behaviors of active duty military members and their dependent spouses generally have found a higher rate of smoking and greater alcohol use in this group compared to their civilian counterparts. However, it is not known whether military retirees and their dependents also report higher smoking and alcohol use compared to the general senior population. Therefore, this study examined cigarette and alcohol use in a group of military retirees (n = 1,359) and dependents (n = 983). Contrary to studies surveying active duty members and their spouses, the present study found that smoking rates and alcohol use among military retirees and dependents were similar to those reported in surveys of the general senior population. In addition, the fact that the majority of retirees (68%) classified themselves as ex-smokers suggests that these individuals may adopt more healthy lifestyles over time. Factors associated with smoking and alcohol use are also presented, along with suggestions for future research. PMID- 7783922 TI - Medical staff resources model and methodology: ambulatory/outpatient services. AB - This paper describes a methodology that has practical applicability in the planning, implementation, and evaluation of ambulatory/outpatient services at site specific health care organizations. Fiscal year 1990 cost and reimbursement data are used for baseline values, however the methodology remains constant, for use in future years, by updating fiscal year by fiscal year as increases occur. This conceptual model can be used by military, other public sector, and civilian community health center ambulatory/outpatient services organizations that require 24 hour medical staff coverage, and economically feasible cost reimbursement accountability. PMID- 7783923 TI - Amputee soldiers and their return to active duty. AB - This study was undertaken to determine the percentage of soldiers who remain on active duty after undergoing a Physical Evaluation Board (PEB) for an amputation. The computerized records of all amputee soldiers who were presented to one of four Army PEBs during an 8-year period (October 1980 to September 1988) were reviewed. Only 11 of 469 soldiers (2.3%, 95% CI 1.2-4.2%) remained on active duty after amputation. Of those who returned to duty, most (6 of 11) sustained partial hand amputations, three had partial foot amputations, and two were below-knee amputees. Among those returning to duty, there were no female soldiers. We conclude that continuation on active duty is a rare event after amputation. Further studies on active duty is a rare event after amputation. Further studies are necessary to define the characteristics associated with active duty service as an amputee and the impact of an amputation on performance of military duties. PMID- 7783924 TI - On being informed you are HIV positive: experiences of Navy service members. AB - This study addressed the experience of being told that one has become infected with the human immunodeficiency virus (HIV) while serving in the United States Navy. Responses to a questionnaire, administered to 150 HIV-positive service members, indicated that feelings of fear, shock, disbelief, and embarrassment were experienced by study participants upon learning of their HIV-positive status. The manner in which their HIV diagnosis was disclosed was generally viewed in favorable terms and more so in recent years relative to the earliest days of the Navy's HIV program. Having a medical officer as a disclosing official was associated with more negative experiences than was the case for other categories of disclosing officials. Lastly, post-disclosure events were often excessively stressful, and no improvement in this regard over 6 years of the Navy's HIV program was evident. PMID- 7783925 TI - Epidemiology of ametropia of U.S. Army recruits. AB - All people attempting to enlist in the U.S. Army must undergo a physical examination that requires a rudimentary vision screening. Those who pass the physical, upon reporting to basic training, are again evaluated and any treatment necessary to allow the recruits to function during their initial indoctrination is provided. Those who fail to see 20/20 O.D. and O.S. with their current spectacles fail the screening and are evaluated by an optometrist. If their condition is not disqualifying, appropriate correction is prescribed. We reviewed the records of all the recruits in a 1-month period who either required spectacles to see 20/20 or failed the screening at the 43rd AG BN (reception). Epidemiological evaluation revealed most to be either simple myopes or myopic astigmats. Hyperopia and hyperopic astigmatism accounted for the next most common diagnosis. Other conditions included anisometropia, antimetropia, amblyopia, keratoconus, and nystagmus. Examinations of these recruits were very limited, with dilated fundus evaluations being performed only when there was a high probability of a disqualifying condition. Therefore, it is unknown what retinal disease or degeneration may be present other than what would be visible with direct ophthalmoscopy. PMID- 7783926 TI - Posttraumatic meningioma: explanation of an epidemiologic dichotomy. AB - A 23-year-old soldier sustained a penetrating gunshot wound to the right frontoparietal region of the head in 1971 while serving in Vietnam. In 1984, he developed headaches and seizures, and a meningioma was found at the cranioplasty site. Recurrent meningiomas, requiring resection, developed at this site in 1988 and 1990. In 1994, he developed right proptosis. An extensive mass involving the right intraorbital region and the anterior and middle cranial fossa was found. Pathological examination of this tumor demonstrated malignant meningioma. Although antecedent head trauma has been implicated as a risk factor for meningioma, epidemiological studies of this association have yielded divergent conclusions. An explanation for this epidemiologic dichotomy is suggested. PMID- 7783927 TI - Spastic quadriparesis, dysarthria, and dysphagia following cervical hyperextension: a traumatic pontomedullary syndrome. AB - A 44-year-old man developed a clinical syndrome characterized by nonprogressive spastic quadriparesis, dysarthria, and dysphagia following a severe cervical hyperextension injury. These clinical features, coupled with normal neuroimaging studies, are consistent with a stretch injury of the corticospinal and corticobulbar tracts at the pontomedullary junction. PMID- 7783928 TI - Military surgery: certification is long overdue. AB - Military surgery is a complex discipline that has progressed far beyond triage and the debridement of battle wounds. The evolution of modern warfare now demands that the combat surgeon be knowledgeable in military tactics, logistics, transport of personnel, trauma surgery, tropical medicine, public health, industrial medicine, and special weapons, as well as have a familiarity with the organizational structure and culture of the military services. This complexity qualifies military surgery as a subspecialty of surgery according to the criteria of the Accreditation Council for Graduate Medical Education (ACGME). Accreditation of military surgery as a defined specialty should be sought because that recognition will produce better care for our troops, improve education of military medical personnel, and stimulate research. PMID- 7783929 TI - The effect of father absence on the psychiatric hospitalization of Navy children. AB - Some Navy families are subject to unusual stress in that the active duty parent may be deployed for several months at a time. This study examined children and adolescents from Navy and civilian families who were admitted to a private psychiatric hospital. Deployment of the father placed Navy children and adolescents at risk for psychiatric hospitalization, but mainly in non-intact families where step-parents or single parents were present. Deployment may strain an already vulnerable family structure in selected Navy families. PMID- 7783930 TI - Current management of carotid atherosclerosis. AB - Carotid atherosclerosis affects thousands of individuals each year. A history of transient ischemic attacks should alert the clinician to the possibility of carotid artery disease. Carotid endarterectomy is of proven benefit in both symptomatic and asymptomatic individuals, with angiographically confirmed carotid stenosis of from 70 to 99%, respectively. Guidelines for the diagnostic and preoperative screening procedures as well as the surgical technique used by the Department of Neurosurgery at the National Naval Medical Center are reviewed. PMID- 7783931 TI - Seasonal symptoms in the sub-Arctic. AB - To obtain information regarding the frequency and severity of seasonal symptoms in the sub-Arctic, 361 Seasonal Pattern Assessment Questionnaires (SPAQ) were collected from four separate populations, all either assigned to Fort Wainwright, in Interior Alaska, or receiving treatment there. The study included both civilian and military personnel, of both genders, over 16 years of age. The mean score on the SPAQ was in the low end of the range of sub-syndromal seasonal affective disorder. Females scored significantly higher than males, the mean score approaching that found in seasonal affective disorder. Active duty females scored higher than civilians, and were found to have symptoms severe enough to qualify as true seasonal affective disorder in 10.9% of cases. The highest scores and highest rates of true seasonal affective disorder were found in a group of 25 Medical Activity (MEDDAC) female non-commissioned officers who were not in patient status. PMID- 7783932 TI - Radiation safety training program at the National Institutes of Health. AB - At the U.S. Public Health Service's National Institutes of Health (NIH), one of the world's largest biomedical and clinical research institutions, 70 to 80% of all research is performed using radiation or radioactive materials. To maintain a safe environment and minimize risks to the health and safety of the employees, patients, visitors, and the surrounding community, a radiation protection program is required. Under U.S. Nuclear Regulatory Commission licenses and NIH policies, the Radiation Safety Branch (RSB), Division of Safety, administers a comprehensive radiation safety program covering over 3,500 NIH laboratories and some 7,000 laboratory and ancillary staff workers. The NIH radiation protection program provides for the effective supervision, control, and monitoring of all radioactive materials and radiation sources at NIH. This includes activities such as radiation exposure monitoring, laboratory inspections, waste management, consulting, environmental monitoring, and training. Training is considered an integral part of the radiation safety program. RSB offers an extensive training program with over 20 different training courses each year. For example, in 1993 some 6,700 employees attended 243 classes. PMID- 7783933 TI - Maxillofacial war injuries in civilians and servicemen during the aggression against Croatia. AB - Although civilian populations have been heavily involved in most of the recent wars and conflicts throughout the world, most reports analyzed casualty data of military personnel, often leaving civilian casualties excluded or underestimated. A comparison of epidemiologic and medical data for maxillofacial injuries between civilians and servicemen (policemen, soldiers, and United Nations Protection Forces) during the aggression against Croatia is attempted. Of the 220 casualties admitted to the Department of Maxillofacial Surgery in Zagreb between August 1991 and December 1992, almost one-fourth were civilians. A significant difference between civilians and servicemen was noted in age and sex distribution. The incidence and severity of maxillofacial and associated injuries is almost equal, and the pattern of injuries is of the same type for civilian and military personnel. PMID- 7783934 TI - War wounds in the Sibenik area during the 1991-1992 war against Croatia. AB - This report presents the analysis of war casualties treated at the Department of Surgery of Sibenik Medical Center during a 5.5-month period, i.e., from the beginning of the aggression in August 1991 to the international recognition of the Republic of Croatia on January 15, 1992. A total of 321 war casualties were treated, 157 of whom were out-patients and 164 in-patients with severe multiple injuries, 39.25% of the wounded were civilians, 10 of whom were children. Fragment wounds from mortar shells, anti-personnel mines, and infantry weapons were the most frequent type of injuries. The most common were injuries of the limbs. Gunshot injuries to the brain had the worst prognosis. Early management of the wounds was of special importance. Stabilization of the fracture using external fixators was indicated in patients with severe, complicated fractures associated with extreme defects of the tissue. Comatose patients with possible intra-abdominal injury presented a specific diagnostic problem, which was best treated by exploratory laparotomy. The overall mortality rate was 2.49%. PMID- 7783935 TI - Orthopedic casualties in an activated National Guard Mechanized Infantry Brigade during Operation Desert Shield. AB - From November 1990 to April 1991, the 48th Infantry Brigade (Mechanized), an Army National Guard unit, was activated under Operation Desert Shield and deployed to the National Training Center, Fort Irwin, California, for training in desert warfare. All casualties requiring care beyond the battalion aid stations were evacuated to the medical company organic to the 48th Brigade. Each of 727 orthopedic patient visits were grouped into one of eight etiologies: trauma, degenerative, overuse, infectious, neoplastic, congenital/pediatric, miscellaneous, and psychiatric. Each case was also classified according to anatomic region, severity, and disposition as well as need for a minor procedure, operation, or referral. Orthopedic casualties in a reserve mechanized infantry brigade undergoing intensive field training primarily arose from four common etiologic/regional presentations: wrist/hand trauma, knee/leg trauma, spine/pelvis degenerative, and ankle/foot overuse. Many of these injuries are predictable consequences of a particular soldier's military occupational specialty and unit mission. PMID- 7783936 TI - Physical health symptomatology of Gulf War-era service personnel from the states of Pennsylvania and Hawaii. AB - We present data on physical health and possible "Gulf War syndrome" from a Congressionally mandated study of over 4,000 active duty and reserve service members from the states of Hawaii and Pennsylvania who served during Operation Desert Storm. We found that deployed veterans report significantly more physical health symptoms than non-deployed veterans that cannot be explained by reasons other than deployment alone. We also identified a subgroup of 178 deployed veterans at risk for possible Gulf War syndrome. We recommend that services collect baseline information from units likely to deploy in the future and update that information regularly. PMID- 7783937 TI - Do Vietnam-era veterans who suffer from posttraumatic stress disorder avoid VA mental health services? AB - It has been suggested that Vietnam veterans who suffer from posttraumatic stress disorder (PTSD) avoid Department of Veterans Affairs (VA) health services because their experiences in the military engendered a profound distrust of the Federal Government and its institutions. Data from a national survey of 1,676 veterans who served during the Vietnam era show that veterans with PTSD were 9.6 times more likely than other veterans to have used VA mental health services; but only 3.3 times more likely to have used non-VA services. After controlling for other factors, veterans suffering from PTSD were 1.8 times more likely than other veterans to have used VA services, but were no more likely to have used non-VA services. Contrary to conventional belief, veterans with PTSD show a preference for VA compared to non-VA mental health services. PMID- 7783938 TI - Evaluation of glucose monitoring devices in the hyperbaric chamber. AB - Diabetic patients may experience fluctuations in whole blood glucose (WBG) levels while receiving hyperbaric oxygen therapy (HBO) resulting in seizure-like activity. Therefore, hyperbaric medical attendants must accurately monitor the WBG levels of these patients during HBO. In addressing this concern, this study evaluated the accuracy and reliability of commercially available glucometers (Glucometer M+, Companion 2, HemoCue, One Touch II, and ExacTech Pen) in the hyperbaric environment. WBG samples were prepared, ranging from 25 to 250 mg/dl, for testing glucometers at ground level and at 2.36 atmospheres absolute (ATA). It was noted that at 2.36 ATA, glucose values increased using the Glucometer M+, but decreased with the Companion 2 and HemoCue. The One Touch II values decreased in the hyperglycemic ranges (> 150 mg/dl), whereas the ExacTech Pen monitor readings increased in the hypoglycemic ranges (< 100 mg/dl). The accuracy of WBG monitors is significantly affected by changes in atmospheric pressure. PMID- 7783939 TI - New studies disputing allegations of bacteriological warfare during the Korean War. AB - In the television series Korea the Unknown War produced jointly by Thames Television (London) and WGBH (Boston) in 1990, General Matthew Ridgway, Commander in Chief of United Nations forces during the Korean War, called the accusations that the United States waged bacteriological warfare "black propaganda." The charges discredited the United States and, despite denials and many international discussions, have not been completely refuted until new. Following studies in archives previously not available for research and after uncovering new sources, many specific examples of black propaganda were discovered that contained false information and lies discrediting the United States. The mechanism of lies, which convinced the Korean population that bacteriological warfare was going on and that the only way not to become victims of the United States' inhuman cruelty was to fight, are shown in this paper. PMID- 7783940 TI - Reversible inactivation of dorsal hippocampus by tetrodotoxin impairs blocking of taste aversion selectively during the acquisition but not the retrieval in rats. AB - The role of the dorsal hippocampus in the different stages of blocking was examined in a taste aversion learning task. Blocking is a learning effect in which one previously conditioned element of a compound makes the conditioning of the added element difficult. An effective blocking procedure with one trial in each stage was tested in unoperated rats. In the first stage, rats drank saccharin and later received lithium chloride by i.p. injection. In the second stage, they were presented with a serial compound saccharin-cider vinegar before lithium injection. In a one-bottle, test a reduced aversion to cider vinegar was observed in this group compared to control groups with no previous saccharin aversion. Bilateral tetrodotoxin (TTX) injection (10 ng/microliters) in the dorsal hippocampus attenuated blocking if this was applied before drinking the compound stimulus during the second stage, but it produced no effect applied either before drinking saccharin in the first stage or before testing. Non specific retrieval deficit produced by TTX injection applied before testing was ruled out in a control group subjected to a conventional cider vinegar aversion learning which showed complete retrieval of the aversion under TTX. It is concluded that the hippocampal function relevant for blocking takes place during the compound phase. PMID- 7783941 TI - S100 immunoreactivity in a subpopulation of oligodendrocytes and Ranvier's nodes of adult rat brain. AB - The Ca(2+)- and Zn(2+)-binding S-100 proteins (S100) are predominantly localized in astrocytes of adult mammalian brain. In addition, light and electron microscopic immunocytochemistry revealed S100 in a small subpopulation of oligodendrocytes. By nuclear morphology and abundance of rough ER and Golgi fields, these cells resembled actively myelinating oligodendrocytes. S100 immunoreactivity was also found in paranodal loops and outer mesaxons of isolated of myelin sheaths. Data suggests that oligodendroglial content of S100 relates to cell turnover and/or myelin repair in the adult rat brain, and that S100 is present during myelin compaction. PMID- 7783942 TI - Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease. AB - In order to establish whether positron emission tomography (PET) can identify metabolic changes in Alzheimer's disease at a presymptomatic stage, we have examined 24 asymptomatic at risk individuals from families with Alzheimer's disease. A significant reduction in global cerebral metabolic rate for glucose was found when compared with 16 age-matched controls. There was also a focal, parieto-temporal deficit similar to, although less extensive than, that found in 18 symptomatic individuals from familial Alzheimer's disease (FAD) pedigrees. Follow up of this cohort will establish whether these metabolic changes relate to a presymptomatic stage of the disease. PMID- 7783943 TI - Cerebroside formation in the peripheral nervous system of normal and Trembler mice. AB - The formation of cerebrosides by the galactosylation of ceramides was investigated in a microsomal fraction prepared from sciatic nerves of normal and Trembler mice. In the control, cerebroside synthesis is observed in the presence of uridine-diphosphate-galactose both from endogenously synthesized [1 14C]stearoyl-sphingosine (C18-ceramide), and from [1-14C]lignoceroyl-sphingosine (C24-ceramide). Cerebroside formation is also demonstrated by studying the galactosylation of exogenous ceramides with UDP[1-14C]-galactose. In the mutant, only trace amounts of labeled cerebrosides are formed from labeled stearoyl sphingosine, whereas with lignoceroyl-sphingosine, no cerebroside synthesis is detected under conditions allowing their formation in the control. However, a higher rate of synthesis of short acyl chain-glucosyl ceramides is observed in the Trembler samples. PMID- 7783944 TI - Inhibitory action of nicotinic antagonists on transmitter release at the neuromuscular junction of the rat. AB - The effects of two nicotinic antagonists, d-tubocurarine (TC) and hexamethonium (HEX) were tested on the rat diaphragm neuromuscular junction during train-of-six stimuli to determine if a second action of these antagonists on evoked release could be demonstrated, in addition to its known impact of blocking the autoreceptor pathway. To minimize the autoreceptor pathway, the preparations were examined under low transmitter release conditions. It was observed that both compounds significantly depressed the end-plate potential amplitudes more than the miniature end-plate potential amplitudes, while also significantly depressing quantal release output. This inhibitory action is contrary to what is observed when transmitter release is high, where feedback regulation via the autoreceptors serves a prominent role. It is concluded that this depressive action on transmitter output contributes to onset of tetanic fade and that when higher concentrations of these antagonists are used this inhibitory action of TC and HEX may override autoreceptor feedback regulation. PMID- 7783945 TI - Nitric oxide is involved in the non-adrenergic, non-cholinergic inhibitory neurotransmission of the pig intravesical ureter. AB - NADPH-diaphorase histochemical staining and electrical field stimulation (EFS) were performed in vitro to investigate whether nitric oxide (NO) is involved in non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission of pig intravesical ureter. NADPH-diaphorase activity was expressed in nerve trunks and thin nerve fibres around arteries and muscular bundles in the intravesical ureter. Relaxations to EFS were tetrodotoxin (10(-6) M)-sensitive which indicates their neurogenic origin. Addition of the NO-synthase inhibitor, L-NG nitroarginine (L-NOARG, 3 x 10(-5) M), abolished the electrically induced relaxations, which were significantly reversed by L-arginine (3 x 10(-3) M). Addition of acidified sodium nitrite (NaNO2, 10(-5)-10(-3) M) evoked concentration-dependent relaxations of ureteral strips which were unaffected by L NOARG. It is concluded that NO synthase is present in nerve fibres and NO seems to mediate the inhibitory neurotransmission of the porcine intravesical ureter. PMID- 7783946 TI - Increased sympathetic nerve discharge without alteration in the sympathetic baroreflex response by serotonin3 receptor stimulation in the nucleus tractus solitarius of the rat. AB - Previous studies have shown that serotonin3 receptor activation in the nucleus tractus solitarius (NTS) increased mean arterial pressure (MAP) and inhibited the cardiac component of the baroreceptor reflex [9]. We have examined the effects of such stimulation upon spontaneous and evoked sympathetic nerve activity. Microinjection of serotonin (10 nmol) into the NTS of halothane-anaesthetized, paralyzed and artificially ventilated rats produced an increase in MAP and lumbar sympathetic nerve discharge which could be completely prevented by prior local microinjection of zacopride, a potent serotonin3 antagonist (200 pmol). In addition, 1-(m-chlorophenyl)-biguanide, a selective serotonin3 receptor agonist, mimicked the sympathoexcitatory effect of serotonin. Since the gain of the sympathetic component of the baroreflex was unaltered after intra-NTS microinjection of serotonin, it could be concluded that serotonin3 receptors activation in the NTS induces a sympathetic activation which is not mediated through an inhibition of the sympathetic baroreceptor reflex arc. PMID- 7783947 TI - Modulatory effects of magnolol on potassium-stimulated 5-hydroxytryptamine release from rat cortical and hippocampal slices. AB - Magnolol, a phenolic constituent of magnolia bark, is a known central nervous system depressant. To examine the possibility that magnolol may elicit its depressant effect by modulating central serotonergic activity, its effect on 35 mM K(+)-stimulated 5-[3H]HT release from rat hippocampal and frontal cortical slices were examined. Inclusion of magnolol (1-100 microM) had no effect on 5-HT release in hippocampal slices but elicited a dose-related inhibition on 5-HT release from cortical slices. The inhibitory effect of magnolol on K(+) stimulated 5-HT release from the cortex was not affected by either antagonists (metergoline, propranolol, and cyproheptadine) (0.01-10 microM) of various 5-HT receptor subtypes or the voltage-dependent sodium channel blocker tetrodotoxin (1 microM). It is concluded that the suppression of brain 5-HT release by magnolol is site-specific, and the suppression of cortical 5-HT release by magnolol is not via the 5-HT autoreceptors at the 5-HT terminals. PMID- 7783949 TI - Growth factors and gangliosides stimulate laminin production by human glioma cells in vitro. AB - Neoplastic cells from intrinsic, neuroectodermal tumours may migrate up to several millimeters away from the original tumour mass into normal nervous tissue. The biological mechanisms underlying this local invasive behaviour of gliomas are poorly understood. We have demonstrated recently that growth factors and cell surface gangliosides are positively involved in human glioma cell adhesion, migration and invasion in vitro. In order to study the mechanism of action of gangliosides and growth factors in this process, their role in the production of laminin, the major component of glioma vascular basal lamina, was investigated. Both growth factors and gangliosides stimulated laminin production in vitro suggesting that these factors increase laminin production in order to enable glioma cells to adhere and then migrate and invade in vivo. PMID- 7783948 TI - Platelet activating factor induces nerve growth factor production by rat astrocytes. AB - During the course of brain injury and inflammation there is an enhanced secretion of neurotrophic substances. We have examined the effect of platelet activating factor (PAF), which has been associated with various pathological conditions in the central nervous system, on the secretion of nerve growth factor (NGF) by astrocytes. Enriched cultures of rat cortical astrocytes were treated with various concentrations of PAF for different periods of time. PAF induced a dose dependent increase in NGF secretion, the maximal increase of 120% obtained with 50 nM PAF after 48 h of treatment. This effect was blocked by the specific antagonist WEB 2086 and was not related to a proliferative response of the cells to PAF. Concomitant treatment of the cells with PAF and tumor necrosis factor alpha resulted in a synergistic increase in NGF secretion. These results indicate that PAF may provide a neurotrophic signal to injured neurons and may cooperate with TNF-alpha in this effect. PMID- 7783951 TI - Cerebral endothelial cells are a major source for soluble intercellular adhesion molecule-1 in the human central nervous system. AB - Immunohistological analysis of tissue sections from human brain revealed that intercellular adhesion molecule-1 (ICAM-1) is mainly expressed on endothelial cells of small vessels, including the subependymal vessels of the choroid plexus. In addition, it is expressed on cerebrospinal fluid (CSF) cells in patients with inflammatory diseases of the central nervous system. Stimulation of confluent monolayers of adult human cerebral endothelial cells with lipopolysaccharide (LPS) or recombinant human tumor necrosis factor-alpha (TNF-alpha) could induce expression and secretion of soluble ICAM-1 in a dose dependent manner. In addition, sICAM-1 was also present in the supernatant from U251 glioma cells. No sICAM was detected in the culture supernatant from activated blood or CSF lymphocytes. Cerebral endothelial cells are therefore a likely source for sICAM-1 in the CSF. PMID- 7783950 TI - Preservation of acetylcholine muscarinic M2 receptor G-protein interactions in the neocortex of patients with Alzheimer's disease. AB - The efficacy of acetylcholine muscarinic M2 receptor-G protein coupling was investigated in Alzheimer's disease and control neocortical membranes by measuring the effects of MgCl2 and 5'-guanylylimidodiphosphate (Gpp[NH]p) on high affinity [3H]oxotremorine-M ([3H]OXO-M) binding. MgCl2 gave similar enhancements of [3H]OXO-M binding in Alzheimer's disease and control occipital cortex. In contrast, MgCl2 enhanced [3H]OXO-M binding was significantly higher in Alzheimer's disease superior temporal cortex, compared to controls. MgCl2 enhanced [3H]OXO-M binding in both the occipital and temporal cortices of the Alzheimer's disease cases was reversed to control levels by Gpp[NH]p. It is concluded that the number of high-affinity muscarinic M2 sites is increased in Alzheimer's disease superior temporal, but not occipital, cortex and that M2 sites in both regions maintain an efficient G-protein coupling. PMID- 7783953 TI - Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit. AB - It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition. PMID- 7783952 TI - Ageing affects cytosolic Ca2+ binding proteins and synaptic markers in the retina but not in cerebral cortex neurons of the rat. AB - Two cerebral cortex areas (frontal and occipital) and the retina of rats varying in age from 0.4 to 30 months were investigated for the expression levels and distribution of two cytosolic high affinity Ca2+ binding proteins, calbindin-28 and calretinin, and of two presynaptic protein markers. Of these latter proteins, one is integral (synaptophysin) the other peripheral (synapsin I) to the synaptic vesicle membranes. In the cortex areas, no significant changes of the markers were observed, except for a drop of calretinin from 0.4 to 2 months, probably related to a stage of neuronal development. In the retina, calbindin-28 decreased progressively during ageing (-40% at 30 months) while calretinin remained unchanged. Concomitantly, the two synaptic vesicle proteins dropped, synaptophysin > 50% and synapsin I > 85%. The role of these changes in sustaining the functional alterations previously described in the retina of aged animals remains to be investigated. PMID- 7783954 TI - Low-affinity nerve growth factor receptor immunoreactivity in the human urinary bladder. AB - The localization of low-affinity nerve growth factor receptor (LNGFR) in the human urinary bladder was examined immunohistochemically using the mouse monoclonal antibody (ME20-4) against human LNGFR. LNGFR immunoreactivity was present in the human urinary bladder. The distribution of LNGFR-positive fibers was more abundant in the mucosa than in the muscle layer. Results also showed that some LNGFR-positive fiber bundles contained tyrosine hydroxylase immunoreactivity. Electron microscopic examination revealed that LNGFR immunoreactivity was located on the surface of Schwann cells, and frequently on the interface of axons and Schwann cells. PMID- 7783955 TI - Intracerebroventricular administration of a nitric oxide-releasing compound, NOC 18, produces thermal hyperalgesia in rats. AB - This study was undertaken to define the role of nitric oxide (NO) in central nociceptive mechanisms by intracerebroventricular injection of an NO-releasing compound, NOC-18, in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. Sixty-nine rats were divided into the seven groups, and the following drugs were injected intracerebroventricularly in 5 microliters of saline: no drug (control) (n = 13), 15 micrograms of NOC-18 (n = 15); 150 micrograms of NOC-18 (n = 9); 100 micrograms of N-nitro-L-arginine methyl ester (L-NAME) (n = 8); 15 micrograms of NOC-18 + 100 micrograms of L-NAME (n = 8); 10 micrograms of methylene blue (MB) (n = 8); 15 micrograms of NOC-18 + 10 micrograms of MB (n = 8). NOC-18 caused a dose-dependent curtailment (7% and 23% decreases for 15 micrograms and 150 micrograms of NOC-18, respectively) of the tail-flick latency during the period from 15 to 120 min. L-NAME caused prolongation (15% maximum) of the tail-flick latency during the period from 15 to 150 min. However, NOC-18-induced hyperalgesia was not influenced by L-NAME. MB also caused prolongation (9% maximum) of the tail-flick latency during the period from 15 to 150 min, and completely blocked the hyperalgesia induced by 15 micrograms of NOC-18. These findings indicate that the NO-cGMP pathway is directly involved in thermal hyperalgesia in the brain. PMID- 7783956 TI - Regional differences in the interaction of the excitotoxins domoate and L-beta oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus. AB - The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus. PMID- 7783957 TI - Binding of Lambert-Eaton myasthenic syndrome IgG to synaptosomal proteins does not correlate with an inhibition of calcium uptake. AB - The immunochemical and functional properties of IgG fractions from patients with Lambert-Eaton myasthenic syndrome (LEMS) were examined in chick and rat synaptosomes. LEMS IgG immunoprecipitated 125I-omega conotoxin GVIA (125I-omega CgTx) labeled N-type calcium channels solubilized from both tissues, and reacted with a 65 kDa protein band in immunoblots of rat synaptosomes. Depolarization induced 45Ca2+ influx into chick synaptosomes was partially inhibited by omega CgTx, whereas influx into rat synaptosomes was insensitive to omega CgTx. No effect of LEMS sera or IgG on 45Ca2+ uptake was apparent in either preparation. PMID- 7783958 TI - Allelic variations in apolipoprotein E and prion protein genotype related to plaque formation and age of onset in sporadic Creutzfeldt-Jakob disease. AB - Prion gene sequence is thought to affect the phenotypic expression of prion disease and the E2 variant of apolipoprotein E (Apo E) can be neuroprotective in dementia. We determined codon 129 of the prion gene and the Apo E variants in Creutzfeldt-Jakob disease (CJD) using PCR and restriction digest. We found a significant correlation between valine at codon 129 of the prion protein gene and the presence of plaque in CJD and a later age of onset in CJD cases possessing the Apo E2 allele. This study provides further evidence that sequence variations in the prion gene can modify disease pathology and the neuroprotection afforded by Apo E2 is not confined to Alzheimer's disease. PMID- 7783960 TI - Extracellular phosphorylation of membrane protein modifies theta burst-induced long-term potentiation in CA1 neurons of guinea-pig hippocampal slices. AB - The involvement of ecto-protein kinase activity in activity-dependent long-term potentiation (LTP) was studied in CA1 neurons of guinea-pig hippocampal slices. Application of 5 microM K-252b, an ecto-protein kinase inhibitor, blocked LTP induced by a theta-burst stimulation (3 bursts composed of 5 pulses at 100 Hz with inter-burst intervals of 200 ms). On the other hand, under 10 microM RK682, an ecto-phosphatase inhibitor, a robust LTP was induced by a weak theta-burst stimulation (3 bursts composed of 3 pulses) which was just at the threshold for the induction of LTP in the control perfusate. These findings suggest that ATP released from presynaptic terminals during the burst stimulation plays an important role in the induction of LTP through phosphorylation of extracellular domains of synaptic membrane proteins, as the substrate for ecto-protein kinase. PMID- 7783959 TI - The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons. AB - The mechanism of ATP-induced long-term potentiation was studied pharmacologically using guinea-pig hippocampal slices. Application of 1-10 microM ATP for 10 min transiently depressed and then slowly augmented the synaptic transmission in CA1 neurons leading to long-term potentiation (LTP). This ATP-induced LTP was blocked by the addition of K-252b, an ecto-protein kinase inhibitor, but was enhanced by the addition of RK682, an ecto-phosphatase inhibitor, both of which do not permeate the cell membrane. These results suggest that ATP applied to the perfusate provides enough substrate for ecto-protein kinase to induce LTP through phosphorylation of extracellular domains of membrane proteins in CA1 neurons. PMID- 7783961 TI - Inhibition of spinal nociceptive neurons by microinjections of somatostatin into the nucleus raphe magnus and the midbrain periaqueductal gray of the anesthetized cat. AB - The effects of somatostatin (SOM) after intravenous application and intracerebral microinjection into the medullary nucleus raphe magnus (NRM) or into the periaqueductal gray (PAG) on the spinal nociceptive transmission was quantitatively studied in the anesthetized cat. Noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons were reversibly depressed to 56.6 +/- 9.7% of the control after systemically applied SOM (7 micrograms/kg i.v.; 7 micrograms/kg per h infusion rate). At 11 of 14 brainstem microinjection sites in the NRM and PAG, SOM (2.5 micrograms/microliter) attenuated the heat evoked responses to 58.9 +/- 6.2% (n = 5) (NRM) and 64.4 +/- 6.3% (n = 6) (PAG) of the control. After microinjection, maximal inhibition was reached within 8-14 min (NRM) or 23-29 min (PAG), respectively. Inhibition was reversible within 60 min after the injection. Thus, SOM has an antinociceptive potency by activating descending inhibition of nociceptive dorsal horn neurons from the NRM and PAG. PMID- 7783962 TI - Increased density of cortical apolipoprotein E immunoreactive neurons in rabbit brain after dietary administration of cholesterol. AB - Rabbits were fed 2% cholesterol diet for 4, 6 and 8 weeks or control diet for 6 weeks. Frontal cortex and hippocampal formation were stained with apolipoprotein E (Apo-E) antibody using standard immunocytochemical methods. The number of neurons expressing the Apo-E epitope and the intensity of Apo-E immunoreactivity increased with increasing time on the cholesterol diet. Because Apo-E chaperones cholesterol in the brain, the data may suggest that elevated circulating levels of cholesterol eventually cause increased cerebral levels. PMID- 7783963 TI - A severe loss of choline acetyltransferase in the frontal cortex of Alzheimer patients carrying apolipoprotein epsilon 4 allele. AB - We measured the activities of choline acetyltransferase (ChAT) in the post mortem frontal cortex in 32 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes. The ChAT values were significantly lower for the AD patients with 2 epsilon 4 alleles than for those with 0 epsilon 4 (ANOVA, P < 0.05). The ChAT activities of AD patients carrying 2 or 1 epsilon 4 alleles and those without the epsilon 4 allele also differed significantly: 16.3 +/- 15.2 versus 30.5 +/- 20.6 pmol/mg protein per min, ANOVA, P < 0.05. However, the AD patients carrying the epsilon 4 allele were significantly younger than those with 0 epsilon 4 allele. The study indicates that AD patients carrying the epsilon 4 allele have a more severe cholinergic deficit than the AD patients without the epsilon 4 allele. PMID- 7783964 TI - The circadian thyrotropin rhythm is delayed in regular night workers. AB - In order to determine whether the circadian thyrotropin (TSH) rhythm is adapted to a night-active schedule, plasma TSH and body temperature were measured for 28 h every 10-min in 8 regular night workers and in 8 day-active subjects. In night workers, the shift of 8-h in the sleep period induced a mean shift of 6 h 30 min of the TSH acrophase which remained located, as in day-active subjects, at about the time of sleep onset. The nadir of the body temperature rhythm was shifted by an equivalent amount and occurred systematically during the sleep period, so that both parameters maintained a fixed phase relationship. TSH and temperature rhythms had similar amplitudes in the two groups. However, mean TSH values in night workers returned more rapidly to basal values. These results demonstrate that, together with body temperature, TSH acrophase is adapted to regular night work, suggesting that TSH may be a good index for evaluating the orientation of the endogenous clock. PMID- 7783965 TI - GABAergic neuronal circuits in the cerebellum of the dogfish Scyliorhinus canicula (Elasmobranchs): an immunocytochemical study. AB - The presence of GABAergic cells and fibres in the corpus cerebelli and auricles of a dogfish, Scyliorhinus canicula, was studied with immunocytochemistry. In both locations, two types of GABA-immunoreactive (GABA-ir) neurons were observed: stellate cells in the molecular layer and Golgi cells in the granular layer. Stellate cell axons gave rise to numerous GABA-ir boutons distributed throughout the molecular layer and a smaller number of boutons which contacted Purkinje cell perikarya. No GABA-ir baskets around Purkinje cells were observed. Golgi cells of the granular layer gave rise to numerous GABA-ir boutons which were located around cerebellar glomeruli. Purkinje cell perikarya and their axon terminals in the cerebellar nucleus were not GABA-immunoreactive. These findings are discussed in terms of the phylogeny of cerebellar circuits. PMID- 7783966 TI - Protein kinase A-dependent increase in frequency of miniature GABAergic currents in rat CA3 hippocampal neurons. AB - The whole-cell configuration of the patch clamp technique was used to study the effect of an intracellular increase in cAMP on the frequency of GABA-mediated miniature post synaptic currents (MPSCs) in neonatal rats from (P6 to P12) CA3 hippocampal neurons in slices. In the presence of tetrodotoxin (1 microM), and kynurenic acid (1 mM) to block ionotropic glutamatergic currents, forskolin, an activator of adenylate cyclase, markedly increased the frequency of MPSCs without affecting their amplitude or kinetics. The inactive forskolin analog, 1,9 dideoxyforskolin (30 microM), had no effect on the frequency of MPSCs. The effect of forskolin was prevented by the specific protein kinase A (PKA) antagonist Rp cAMP (30 microM). It is concluded that stimulation of PKA potentiates spontaneous GABA release in immature hippocampal neurons. PMID- 7783967 TI - Organization of preparatory postural responses for the initiation of lateral body motion during goal directed leg movements. AB - Postural responses preceding single leg flexion movements were examined in human subjects with respect to a hypothesized primary role of the hip joint abductor adductor musculature in initiating lateral body motion during alterations in stance. The results indicated a speed sensitive interlimb response organization compatible with predictions based on a mechanical model. In conjunction with other recent studies, the findings may be indicative of a common organizational substrate for the initiation of laterally directed motion of the body. PMID- 7783968 TI - The bipotential glial progenitor cell line can develop into both oligodendrocytes and astrocytes in the mouse forebrain. AB - Oligodendrocyte-type 2 astrocyte (O2A) progenitor cells in vivo might differentiate into oligodendrocytes. To examine the influence of the brain micro environment on the differentiation, a bipotential glial cell line from the mouse cerebrum, designated OS3 cells, was implanted into the telencephalon of infant and adult mice. About a half of the OS3 cells injected into 1-week postnatal brain expressed galactocerebroside (GalC), and even myelin basic protein, which were not observed to be expressed in vitro. By contrast, in the brain over 6 months postnatally, many OS3 cells expressed glial fibrillary acidic protein, and did not express much GalC. These findings suggest that the differentiation of glial cells is controlled by stage specific factors in the brain. PMID- 7783970 TI - Expression of messenger RNA for somatostatin receptor subtype 4 in adult rat brain. AB - The distribution and cellular localisation of somatostatin receptor subtype 4 (SSTR4) was investigated in the adult rat brain using the technique of in situ hybridisation with subtype specific oligonucleotide probes. Somatostatin receptor subtype 4 was found mainly in the hippocampus CA1 > CA2 > CA3 pyramidal cells and in the pyramidal cells in layers (IV-VI) of the cerebral cortex. Reverse transcription-PCR with SSTR4 specific primers confirmed the tissue distribution revealed by in situ hybridisation. PMID- 7783969 TI - Intracranial microdialysis of salicylic acid to detect hydroxyl radical generation by monoamine oxidase inhibitor in the rat. AB - The effect of pargyline, a monoamine oxidase inhibitor, on the generation of hydroxyl free radicals (OH) was investigated using striatal microdialysis. Salicylic acid in Ringer's solution (0.5 nmol microliter-1 min-1) was infused through a microdialysis probe to detect the generation of hydroxyl radicals (OH) as reflected by the formation of dihydroxybenzoic acid (DHBA) in the striatum. When pargyline (100 nmol microliter-1 min-1) was infused in rat brain, the level of 3,4-dihydroxyphenylacetic acid (DOPAC) gradually decreased in a time-dependent manner. In addition, a marked elevation of DHBA was observed. The present results indicate that accumulation of dopamine (DA) in the extracellular fluid elicited by pargyline can be auto-oxidized, which in turn leads (possibly by an indirect mechanism) to the formation of cytotoxic OH free radicals. PMID- 7783971 TI - Postnatal changes in glutamate binding in the lower medulla of the rat. AB - Changes in [3H]glutamate (Glu) binding occurring in the lower medulla of the rat between birth (P0) and adulthood (P72) were investigated on cryostat sections using in vitro receptor autoradiography. Densitometric measurements were performed in both autonomic (nucleus tractus solitarii, dorsal motor nucleus of the vagus nerve, ventrolateral medulla) and non-autonomic (inferior olive, spinal trigeminal nucleus) medullary regions. In all these areas, binding densities peaked at P9 and then gradually declined. Values close to those measured in adult animals were reached by P23-P30. These data indicate that glutamatergic neurotransmission within the lower medulla undergoes developmental changes during the early postnatal period. They thereby suggest that the neural circuits essential in organizing autonomic functions are still immature at birth. PMID- 7783972 TI - Phrenic responses to contralateral spinal stimulation in rats: effects of old age or chronic spinal hemisection. AB - Serotonin reveals ineffective spinal pathways from the C2-lateral funiculus to contralateral phrenic motoneurons in young adult rats with acute spinal hemisection. We tested the hypothesis that old age (1.5-2 years) or chronic hemisection (3-5 days) strengthens these pre-existing crossed spinal pathways. There were no consistent differences between young adult rats with acute hemisection versus young adult rats with chronic hemisection or old rat with acute hemisection except that one long-latency phrenic excitation could not be elicited in old rats. The results indicate that neither old age nor chronic hemisection strengthens crossed-spinal pathways, but that old age may selectively diminish spinal pathways involved in the neural control of breathing. PMID- 7783973 TI - Opening of brain potassium-channels inhibits the ACTH-induced behavioral syndrome in the male rat. AB - In adult male rats, the intracerebroventricular (i.c.v.) injection of pinacidil, a potassium channel opener, at the doses of 100, 200 or 300 micrograms/rat, dose dependently reduced the display of the most typical behavioral symptoms (excessive grooming, stretching, yawning, penile erections) induced by the i.c.v. administration of ACTH-(1-24) (4 micrograms/rat). These data indicate that the complex mechanism of the melanocortin-induced behavioral syndrome involves closure of potassium channels in target neurons, and provide further experimental support to the idea that melanocortins are functional antagonists of opioids. PMID- 7783975 TI - The effect of paroxetine on 5-HT efflux in the rat dorsal raphe nucleus is potentiated by both 5-HT1A and 5-HT1B/D receptor antagonists. AB - Serotonin (5-HT) efflux in slices of rat dorsal raphe nucleus (DRN) was evoked by pseudo one pulse electrical stimulation (20 pulses at 100 Hz, 190 ms train duration) and measured, along with 5-HT uptake, by fast cyclic voltammetry (FCV). The selective serotonin re-uptake inhibitor (SSRI) paroxetine (10(-7) M) increased 5-HT efflux to 147 +/- 6% of pre-drug values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 443 +/- 38%. The non-selective 5-HT1 antagonist methiothepin (2 x 10(-7) M) increased 5-HT efflux to 147 +/- 9% at maximum but had no effect on uptake half-life. In contrast, (+)-WAY 100135 (10( 6) M) and GR 127935 (5 x 10(-8) M), selective antagonists at 5-HT1A and 5-HT1B/D receptors, respectively, affected neither 5-HT efflux nor uptake. When given in combination with paroxetine, the antagonists significantly increased the effect of paroxetine on efflux: methiothepin to 228 +/- 24% (P < 0.001), (+)-WAY 100135 to 212 +/- 31% (P < 0.05) and GR 127935 to 203 +/- 23% (P < 0.01). These data suggest that, under these experimental conditions, DRN 5-HT autoreceptors are tonically activated in the presence of the uptake blocker and that the antagonists act by blocking this counteracting autoinhibitory tone. The data also strongly indicate that 5-HT efflux in the rat DRN is under the control not only of 5-HT1A but also of 5-HT1B/D receptors. PMID- 7783974 TI - Protein L-isoaspartyl methyltransferase: developmentally regulated gene expression and protein localization in the central nervous system of aged rat. AB - We have cloned a cDNA encoding protein L-isoaspartyl methyltransferase (PIMT) and characterized gene expression in the development, maturation, and the aging process of the central nervous system by RNA blot analysis, western blot analysis, and immunohistochemistry. PIMT transcript was detected in rat embryonic brain and showed a linear up-regulation during the maturation of the brain and maintained its level in aged rat brain. Immunoblot analysis also supported a linear increase in the amount of PIMT in the maturation process of rat brains. An immunohistochemical study showed that PIMT is strongly expressed in neurons and weakly but definitively in glial cells and oligodendrocytes. These immunoreactivities significantly increased in some neurons of the hippocampus, cerebral cortex, and the brain stem of aged rat brain. The present results suggest that the expression of PIMT is associated with the amount of racemized/isomerized proteins accumulated during the developmental and aging process of the central nervous system. PMID- 7783977 TI - Temporal analysis of neuropeptide Y expression in the rat trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve. AB - Temporal changes in the appearance and the cell-size spectrum of neuropeptide Y (NPY)-like immunoreactive (IR) cells in the rat trigeminal ganglion (TG) following peripheral axotomy of the inferior alveolar nerve (IAN) were studied by retrograde neuronal tracing with True Blue (TB) and immunohistochemistry for NPY. The number of labeled cells following application of TB to the cut-end of the IAN increased rapidly up to 3 days, and was maintained at a constant level thereafter. The size distribution of cross-sectional areas of TB-labeled cells was similar at 3 days and afterwards. NPY-IR cells, which were not detected in the normal TG, appeared on the first day following axotomy, and increased gradually in number reaching a maximum at 14 days. The frequency histogram of the cross-sectional areas of NPY-IR cells was similar at 3 days and afterwards. The present results indicate that the effect of nerve injury on the levels of NPY expression in the sensory neurons began soon after nerve injury, reaching a maximum around 14 days, and that induction of NPY in the sensory neurons occurred in the same cell size-specific manner for a long period. PMID- 7783976 TI - Day-night differences in the contents of vasoactive intestinal peptide, gastrin releasing peptide and Arg-vasopressin in the suprachiasmatic nucleus of rat pups during postnatal development. AB - To investigate the developmental features of peptide levels in the suprachiasmatic nucleus (SCN), the contents of vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP) and Arg-vasopressin (AVP) were measured in punched-out SCN tissue from rat pups on postnatal days (PD) 4, 15 and 20 using a specific enzyme immunoassay. The VIP content was high at night, and the day-night difference was largest at PD4 throughout the developmental stage. GRP and AVP contents increased following the maturation. GRP levels were higher during the dark than the light period from PD4 to PD20. Subjective day-night differences were also observed in blinded pups. Our results indicate that VIP, GRP and AVP in the SCN already show a diurnal rhythm in the SCN during the nursing period. PMID- 7783978 TI - Influence of acute arterial hypertension on blood-brain barrier permeability in streptozocin-induced diabetic rats. AB - The effect of acute arterial hypertension on blood-brain barrier (BBB) permeability was studied in streptozocin-induced diabetic rats using Evans blue as a barrier tracer. Four groups of rats were studied: Group 1, normotensive normoglycemia; Group II, normotensive+diabetes mellitus; Group III, arterial hypertension+diabetes mellitus; Group IV, arterial-hypertension+normoglycemia. During adrenaline-induced acute arterial hypertension the mean arterial blood pressure increased in both non-diabetic and diabetic animals. Changes in BBB permeability were observed in 52% of the non-diabetic rats, and in 72% of the diabetic rats after adrenaline-induced acute arterial hypertension. Mean levels of Evans blue in the whole brain were found to be 0.63 +/- 0.1 mg% in non diabetic and 0.90 +/- 0.2 mg% in diabetic rats. The difference between the non diabetic and the diabetic rats was found to be statistically significant (P < 0.01). From these results it was suggested that the extravasation of Evans blue albumin is more pronounced in the brains of diabetic rats in comparison with non diabetic rats after adrenaline-induced acute hypertension, which is indicative of changes in BBB permeability due to diabetes mellitus. PMID- 7783979 TI - Nitric oxide mediates neuropathic pain behavior in peripherally denervated rats. AB - The involvement of spinal cord nitric oxide (NO) in the development of autotomy, a proposed behavioral model of denervation pain, was studied in sciatic and saphenous nerves transected rats injected intrathecally, 10-15 min prior to neurectomies, with NG-nitro-L-arginine methyl ester (L-NAME, 20-500 nmol), NG nitro-D-arginine methyl ester (D-NAME, 500 nmol), L- or D-arginine (5 mumol), and 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP, 100 and 200 nmol). Self-inflicted lesions were scored daily for 8 weeks. The main effects on autotomy were: (1) a significant suppression in rats injected with L-NAME (500 nmol), but not with D-NAME; (2) a significant potentiation after L-arginine, but not D-arginine; and (3) a significant potentiation with 8-Br-cGMP, which was blocked by co-administration of L-NAME. These findings indicate that autotomy in rats can be modulated by blocking or enhancing nitroxidergic transmission at lumbosacral level, and suggest new therapeutic approaches for the prevention of certain pain syndromes, such as phantom limb pain. PMID- 7783980 TI - Glutamate-induced calcium responses in rat primary cortical cultures are potentiated by co-administration of glutamate transport inhibitors. AB - The effects of glutamate uptake inhibitors on the L-glutamate-induced increase in intracellular calcium concentrations were assessed in rat primary cortical cultures. The glutamate (10 microM)-induced rise in intracellular calcium concentrations was strongly and dose dependently increased and prolonged by simultaneous administration of micromolar concentrations of the reference glutamate transport inhibitors, L-trans-pyrrolidine-2,4-dicarboxylate (PDC) and D or L-threo-beta-hydroxyaspartate. PDC in concentrations up to 10 microM showed no effect on intracellular calcium when administered alone. The anticancer drug tamoxifen, which was found to be effective as a glutamate transport inhibitor, did not increase but prolonged the cellular calcium response to glutamate, indicating that it had a different mechanism of action compared to that of standard glutamate transport inhibitors. The findings suggest that compounds which inhibit the glutamate transporter may potentiate the excitatory glutamatergic signal of cultured neurons when administered together with glutamate. PMID- 7783981 TI - Cerebral vascular amyloid deposition in rabbits with induced thyroglobulin immunity. AB - Cerebral amyloid angiopathy (CAA) occurs in humans along with the neuritic amyloid plaques in Alzheimer's disease, in several familial (inherited) syndromes, and in a sporadic form that increases in prevalence with age to attain a rate of about 60% after age 90. In the non-Alzheimer conditions, it is often accompanied by cerebral hemorrhage and sometimes also by dementia. We report here the experimental induction of cerebrovascular amyloid (CVA) in thyroglobulin (Tg) immunized rabbits. The vascular deposits in these rabbits are comparable to that seen in humans in that they primarily involve arterioles, venules, and capillaries and exhibit microscopic and ultrastructural characteristics similar to the human lesion. Prominent congophilic vascular lesions in the brain were seen in three out of six Tg-immunized rabbits, whereas less striking basement membrane thickening was evident in three other experimental animals, probably reflecting individual variations in vascular responses to actively induced Tg immunity. Occasional primitive amyloid plaques were also encountered adjacent to vascular lesions. These observations are of particular interest since in other experimental models, cerebral vascular amyloid deposits have not been observed, thus suggesting that immunopathogenic events induced by active Tg immunization may be unique in their effects on the cerebral vasculature. PMID- 7783982 TI - Reciprocal control of inflammatory cytokines, IL-1 and IL-6, and beta-amyloid production in cultures. AB - To investigate the role of IL-6 in the pathogenesis of Alzheimer's disease (AD) its effect on amyloid precursor protein (APP) mRNA expression was evaluated. The levels of APP mRNA were determined by Northern blot analysis in primary cultured rat cortical neurons and glial cells exposed to IL-6 (50-200 ng/ml). The cytokine increased neuronal APP mRNA expression about 100% at the highest dose after 6 h of exposure. APP mRNA expression was unaffected in astroglial cells exposed to IL 6. Since IL-1 beta also increased neuronal APP mRNA, the combination of IL-1 beta and IL-6 was tested. The effects were partially additive. The ability of beta amyloid fragment 25-35 to induce IL-1 or IL-6 mRNA was also investigated in astroglial cells. IL-1 beta mRNA was strongly induced by beta 25-35 (25-100 microM) while the expression of IL-6 mRNA remaining unchanged. The results suggest roles for both IL-1 and IL-6 in the neuronal mechanisms related to beta amyloid protein deposition in AD. PMID- 7783983 TI - Presynaptic A2-adrenoceptors and neuropeptide Y Y2 receptors inhibit [3H]noradrenaline release from rat hypothalamic synaptosomes via different mechanisms. AB - Presynaptic receptors may reduce transmitter release with different mechanisms. Both the alpha 2-agonist, clonidine and the Y2-agonist, neuropeptide Y fragment 13-36 (NPY 13-36), induce a concentration-dependent inhibition of the 4 aminopyridine (4-AP)-evoked [3H]noradrenaline ([3H]NA) release from hypothalamic synaptosomes. Changes in alpha 2- and Y2-modulation of noradrenaline (NA) release were observed by lowering the calcium influx with the use of omega-conotoxin (omega-CgTx), a calcium-channel blocking agent. In these experimental conditions, clonidine was less active, whereas NPY 13-36 preserved its efficacy. It therefore seems possible that presynaptic alpha 2-adrenoceptors can primarily inhibit NA release by reducing calcium influx via voltage-sensitive calcium channels (VSCC), while Y2-receptors may inhibit the intracellular release process with a mechanism independent of the calcium entry. PMID- 7783984 TI - Antiretroviral treatment of HIV infection. PMID- 7783985 TI - Anaesthetists, errors in drug administration and the law. AB - AIM: To document the problem of drug administration error in anaesthesia in New Zealand, with regard to: prevalence (in context of the total number of drugs that might be administered during an anaesthetist's career); preventative strategies; and anaesthetists' perceptions concerning the medicolegal environment prevailing in New Zealand. METHODS: A questionnaire was posted to a random sample of 75 New Zealand anaesthetists. Drug administrations per anaesthetic were counted on a random sample of anaesthetic records at Green Lane Hospital. Ten anaesthetists were asked the number of anaesthetics administered per year. RESULTS: Eighty-nine percent of 66 respondents reported at least one error of drug administration, and 12.5% had actually harmed patients. There was no relationship between any preventative strategy and frequency of error. All respondents were concerned about the possibility of manslaughter charges arising from a drug error; 57% thought the medicolegal environment in New Zealand impacted adversely on their practice; 83% thought it might impede the reporting of errors. There seems to be no definitive strategy for the elimination of drug error. CONCLUSION: Error is inherent in drug administration in anaesthesia, as it is in any complex human endeavour; therefore it is illogical to treat it as necessarily criminal. Instead, effort and resources should be aimed at rational initiatives to reduce this worrying problem. PMID- 7783986 TI - Prevalence of childhood asthma symptoms in an industrial suburb of Christchurch. AB - AIM: In response to community concern about the possible respiratory effects of emissions from a fertiliser plant, a study was carried out to determine whether the prevalence of asthma symptoms in 5-8 yr old children in an industrial suburb of Christchurch (Hornby) was the same as in the rest of Christchurch. METHODS: A sample of 646 children aged 5-8 years in Hornby was compared with 1183 6-7 year old children randomly selected from schools throughout the Christchurch metropolitan area. The Christchurch sample was part of the International Study of Asthma and Allergies in Childhood (ISAAC) carried out during 1993. ISAAC questionnaires on respiratory symptoms with some additional questions about smoking and pets were answered by the caregivers of the children sampled. RESULTS: Response rates were 97% in Hornby and 94% in Christchurch. Of the sample, 29% (Hornby) and 27% (Christchurch) had 'wheeze in the last 12 months' while 45% of Hornby and 44% of Christchurch children had 'ever wheezed', 28% had 'ever had asthma'. Significantly more children in Hornby (44%) were exposed to passive smoking compared to Christchurch (29%). Indoor pets were present in 73% and 67% of homes, respectively. CONCLUSION: There was no evidence of an increase in asthma symptoms reported in children in the industrial area of Hornby. PMID- 7783987 TI - Pregnancy in renal transplant recipients: the Christchurch experience. AB - AIM: Assess the pregnancies of our female renal transplant recipients and to document long term maternal and fetal outcome. METHODS: Between 7 June 1972 and 31 December 1992 112 females had at least one renal transplant. Sixty-four of these 112 women were in the reproductive age and had a functioning graft. RESULTS: Nine women had 16 pregnancies which resulted in 11 live births and three first trimester abortions. Two unplanned pregnancies were terminated. Mean age at transplantation was 17.2 yr [range 16-22.5 yr] and mean interval from transplant to pregnancy was 6.8 yr [range 1.8-9.0 yr]. Prednisone and azathioprine were used in all patients and cyclosporin in five. For seven of the successful pregnancies plasma creatinine remained < or = 0.10 mmol/L. One of these women developed allograft nephropathy 5 years after delivery and returned to dialysis 9 years later. For the other four successful pregnancies the preconception plasma creatinine was 0.12-0.14 mmol/L. The woman with two successful pregnancies had a halving of glomerular filtration rate during the second pregnancy, but it has remained stable for 15 years; one was poorly compliant with her immunosuppressive regimen and reached endstage renal failure two years after delivery; one developed cyclosporin nephrotoxicity, but 18 months later renal function was stable after a dosage reduction. Ten infants were delivered by caesarean section, four of them urgently. Three babies were preterm and five growth retarded. One died of sudden infant death syndrome at four months. All other infants developed normally. CONCLUSION: There is no contraindication to pregnancy in female transplant recipients who have stable graft function and controlled blood pressure. Management of such pregnancies should be by shared obstetrical/nephrological/paediatric care. PMID- 7783988 TI - Triclonal gammopathy in a woman with nonHodgkin's lymphoma. PMID- 7783989 TI - Funding long term care for elderly people. AB - Asset testing of elderly people in long term care discriminates unfairly on grounds of age in two ways: only elderly people are charged for public hospital inpatient care and only for elderly people are public health system charges determined by assets not income. In this paper it is argued that the essential requirement for a public health system is that it is universally and promptly available to every person, irrespective of a person's ability to pay. This does not preclude direct charges. The costs for long term care should be met by charges for living and accommodation expenses and any charge for medical and nursing costs should be determined by income and not asset testing. There is no justification for charging for medical and nursing inpatient costs in long term care and not in other areas of public hospital care. If direct charges have to be made for inpatient care, then in the interests of equity, and to achieve adequate funding for the public health system, direct charges for such care should be for acute as well as long term care and for the young and middle aged as well as for the elderly, providing these charges do not preclude any person receiving necessary care. PMID- 7783990 TI - The Paediatric Society of New Zealand: passive exposure of children to environmental tobacco smoke. PMID- 7783991 TI - The management of hypertension. PMID- 7783993 TI - Nocturnal leg cramps in the elderly. PMID- 7783992 TI - Treatment of basal cell carcinoma with intralesional interferon alpha-2a. PMID- 7783994 TI - No measles parties. PMID- 7783995 TI - Skin reactions and terfenadine. PMID- 7783997 TI - Who should treat the infertile couple? PMID- 7783996 TI - The potential adverse effects of soybean phytoestrogens in infant feeding. PMID- 7783998 TI - Osteitis pubis: a review. AB - Osteitis pubis is a painful, noninfectious inflammatory condition that involves the pubic bone, symphysis, and surrounding structures. Initially associated with urologic procedures, osteitis pubis has been described as a complication of various obstetrical and gynecological procedures including vaginal deliveries. An incidence of approximately 2 to 3 percent has been observed after the Marshall Marchetti-Krantz urethropexy. Although the pathogenesis of osteitis pubis is not clear, periosteal trauma seems to be an important initiating event. Pain is the primary symptom associated typically with difficulty in ambulation and the characteristic "waddling gait." A low grade fever, elevated sedimentation rate, and mild leukocytosis may be observed. Radiographic findings which include reactive sclerosis, rarefaction, and osteolytic changes lag behind the symptoms by about 4 weeks. The major differential diagnosis is osteomyelitis; however, the self-limiting nature and its response to nonantibiotic therapy indicates that osteitis pubis is a separate clinical entity. Treatment is directed at the associated inflammation with most minor cases responding to antiinflammatory agents and bedrest. Other more recalcitrant cases require more involved therapy including systemic steroids and rarely surgical resection. The diagnosis of osteitis pubis should be considered when pelvic pain is present in association with potential trauma to the symphysis pubis. Also, with more women participating in sporting activities patients may present to the physician with osteitis pubis related to athletic injury. PMID- 7783999 TI - Pheochromocytoma in pregnancy: case report and review of the literature. AB - Pheochromocytoma is a rare disease that may occur during pregnancy. Only a few hundred cases have been published in the literature. Manifestations include hypertension with various clinical presentations, possibly resembling those of pregnancy-induced hypertension, or pre-eclamptic toxemia. Differentiation of these conditions is not always feasible, thus creating a serious risk, because fetal and maternal morbidity and mortality are far higher with pheochromocytoma. Biochemical measurements of catecholamines and their metabolites are apparently a convenient way to establish diagnosis during pregnancy, inasmuch as interpretation of radiological evaluation is complicated by the gravid uterus, and might even be potentially dangerous due to the use of ionizing radiation. More sophisticated methods for evaluation are not always practical during pregnancy. Medical treatment aims at controlling symptoms, mandating the use of alpha- and beta-receptors blockade medication. Surgical intervention is the only possible curative method available, but the critical issue is probably to identify the exact timing during the course of pregnancy for such intervention, or the ability to control symptoms until delivery. Although malignant transformation of pheochromocytoma have been reported, it is extremely uncommon. The overall prognosis is mainly affected by early diagnosis, and multidisciplinarian management. PMID- 7784000 TI - Combined antenatal vitamin K and phenobarbital therapy for preventing intracranial hemorrhage in newborns less than 34 weeks' gestation. AB - ok--q----_xD-xD whether maternal antenatal therapy with vitamin K and phenobarbital prevents intracranial hemorrhage in premature newborns. METHODS: Women at high risk for spontaneous or indicated premature delivery before 34 weeks' gestation were randomly assigned to receive either placebo or vitamin K and phenobarbital. All patients received betamethasone and antibiotics and were managed uniformly by a single perinatal group in one hospital. All newborns were managed uniformly in the same nursery by one neonatal group. Two independent interpretations of neonatal head ultrasound examinations were obtained. RESULTS: The duration of gestation at study entry and at delivery were similar in the placebo (181 mothers) and treatment (191) groups. With the hospital radiology group (the primary interpreter), the incidence rates of severe intracranial hemorrhage (8 versus 7%) and mild intracranial hemorrhage (38 versus 32%) were similar for both groups. With the secondary interpreter (a single pediatric radiologist), the incidence rates of severe intracranial hemorrhage (9 versus 7%) and mild intracranial hemorrhage (27 versus 26%) were also similar. Neonatal mortality was equivalent in both the placebo and treatment groups (8 versus 10%). CONCLUSION: Combined antenatal therapy with vitamin K and phenobarbital does not reduce the frequency or severity of intracranial hemorrhage in premature newborns. PMID- 7784002 TI - A computer model of uterine contractions based on discrete contractile elements. AB - OBJECTIVE: To predict uterine contraction waveforms using a microcomputer-based model of uterine activity based on discrete contractile elements, varying the shape of the model, total number of cells, and pacemaker locations. METHODS: The model is a hollow ovoid composed of discrete contractile elements (cells) that propagate electrical impulses, generate tension, and have defined contracting and refractory periods. Each cell contacts eight surrounding cells and propagates impulses iteratively from cell to cell. Contraction pressure is the sum of the tension contributions by contracting cells. Sample contraction waveforms were generated based on various numbers of cells organized in ovoids with long:short axis ratios of 1:1, 3:2, and 2:1, with one or two pacemakers at varying positions. RESULTS: Contraction waveforms are altered by altering the shape of the matrix, but not by increasing the number of contractile elements. The vertical placement of the pacemaker has a dramatic effect on the shape and symmetry of contractions, including the development of patterns characteristic of "dysfunctional" uterine contractions. CONCLUSION: Abnormal uterine contraction patterns may result from pacemaker activity in unusual locations, such as mid uterus. Further refinement of this computer model of uterine activity may contribute to a better understanding of the genesis of normal and abnormal intrauterine pressure waveforms and their relationship to the progress of labor. PMID- 7784001 TI - The effect of maternal obesity on the accuracy of fetal weight estimation. AB - OBJECTIVE: To determine if maternal obesity affects the accuracy of either clinical or sonographic fetal weight estimations. METHODS: In a year-long study, 998 singleton pregnancies of 26-43 weeks' gestation underwent both clinical (Leopold) and sonographic (Shepard and Hadlock) fetal weight estimation within 5 days of delivery (mean 1.1, 95% confidence interval 1.0-1.3). Patients were stratified into four different groups based on increasing maternal body mass index (BMI): underweight (less than 19.8), normal weight (19.8-26.0), overweight (26.1-29.0), and obese (more than 29.0). The various estimations of fetal weight were compared with actual birth weight, and the mean absolute percent error was calculated for each specific method and analyzed among the four BMI groups. RESULTS: For each method of weight estimation, there was no difference (specifically, no increase) in the magnitude of the absolute percent error with increasing maternal obesity. Regardless of maternal size, almost half of the weight predictions were within 5% of the actual birth weight. CONCLUSION: Increasing maternal obesity does not alter or decrease the accuracy of either clinical or sonographic fetal weight estimations. Therefore, fetal weight predictions provide equally accurate and valid guidelines for determining management decisions in women, regardless of body size. PMID- 7784003 TI - Gender influences on earnings of obstetrician-gynecologists. AB - OBJECTIVE: To test the hypothesis that the observed difference in earnings between male and female obstetrician-gynecologists could be explained by variations in productivity and human capital. METHODS: Data from a 1991 national survey of ACOG Fellows were used to provide a descriptive analysis of male and female obstetrician-gynecologists' demographic characteristics, net income, experience, practice characteristics, workload, and practice activities. Variables found to have a significant impact on net income or to vary significantly by sex were included in a multiple regression analysis. RESULTS: Twenty-one percent of the 1286 survey respondents were female obstetrician gynecologists. Women were almost twice as likely as men to be in salaried positions (P < .001) and more than twice as likely to have less than 10 years of experience (P < .001). Women reported fewer annual patient-contact hours (P < .05) and performed fewer than half as many hysterectomies (P < .001). Average annual earnings for women were 71% of men's annual net income (P < .001). The multivariate regression analysis found that male-female differences in the factors included in the analysis (ie, workload, experience, practice type) resulted in an 18.7% male-female income gap. The analysis also revealed an income gap of 14.2% that was not accounted for by differences in the objective factors included in the model. CONCLUSION: More than half of the overall male-female income gap was explained by differences in personal and practice characteristics. However, female obstetrician-gynecologists earned 14.2% less than men, after controlling for variations in productivity and human capital. PMID- 7784004 TI - Screening and treatment of asymptomatic bacteriuria of pregnancy to prevent pyelonephritis: a cost-effectiveness and cost-benefit analysis. AB - OBJECTIVE: To compare the effectiveness, benefits, and costs of two asymptomatic bacteriuria screening and treatment strategies to prevent pyelonephritis in pregnancy. METHODS: A decision analytic model was created to compare strategies based on either 1) a leukocyte esterase-nitrite dipstick, or 2) on urine culture, with a policy of no screening or treatment. A literature search was conducted to generate probability estimates. Cost estimates were based on a local pharmacy and laboratory survey and supplemented by recent literature estimates. Sensitivity analyses were performed over wide ranges of probability and cost estimates. RESULTS: Under baseline assumptions, no screening resulted in 23.2 cases of pyelonephritis per 1000 pregnancies, versus 16.2 cases with the dipstick strategy and 11.2 with the culture strategy. The cost of screening and treatment of asymptomatic bacteriuria per 1000 pregnancies was $1968 with dipstick and $19,264 with culture. The cost of treating pyelonephritis with no screening was $57,562, versus $40,257 with dipstick and $27,832 with culture. Therefore, both the dipstick strategy and the culture strategy were cost-beneficial (based on a pyelonephritis cost of $2485) when compared with no screening. However, because it cost $3492 to prevent each additional case of pyelonephritis with culture that was not prevented by dipstick, the culture strategy was not cost-beneficial compared with the dipstick strategy. These results were sensitive to varying estimates for the prevalence of asymptomatic bacteriuria, the rate of progression of asymptomatic bacteriuria to pyelonephritis, the sensitivity of the dipstick, culture costs, and the cost of a case of pyelonephritis. CONCLUSION: When compared with a policy of no screening, screening for and treatment of asymptomatic bacteriuria to prevent pyelonephritis in pregnancy is cost beneficial whether based on the leukocyte esterase-nitrite dipstick or on urine culture. However, the culture strategy is not cost-beneficial when compared with the dipstick strategy. PMID- 7784005 TI - Routine statistical screening revisited. PMID- 7784006 TI - Detection of human parvovirus B19 DNA by nested polymerase chain reaction. AB - We describe the development of a nested polymerase chain reaction (PCR) technique used to detect human parvovirus B19 DNA. It was performed in a two-step reaction, first with a pair of outer primers, then with a pair of inner (ie, nested) primers. Primer sequences were selected in the VP1 gene, corresponding to the capsid protein, of human parvovirus B19. To establish the nested PCR assay, the plasmid pGEM-1 containing almost the entire coding sequence of a human parvovirus B19 isolate was used. The nested PCR could detect up to 1.8 x 10(-3) ag of B19 DNA, equivalent to 10(-4) genomes, by electrophoresis. No amplification product was detected by gel electrophoresis when the reaction mixture contained human placental DNA, cytomegalovirus DNA, and sterile distilled water as templates. We used this assay to evaluate four cases of maternal B19 infection that were diagnosed by determination of the presence of anti-B19 immunoglobulin-M in maternal serum. The advantages of our nested PCR for detecting B19 DNA are plating simplicity, safety, sensitivity, and specificity. Our results suggest that this method may have general applicability in the evaluation of nonimmune hydrops fetalis and in the documentation of the natural history of fetal infection with B19 when applied to specimens of amniotic fluid or fetal blood. PMID- 7784007 TI - Modifying training attitudes and practice during health care reform. AB - Health care reform has focused on the high cost of care today. To comply with proposed changes, new attitudes, training, and practice patterns are needed. Constant concern about the cost of diagnosis must exist, and only proven therapies can be justified. PMID- 7784008 TI - Ideal residency curriculum in reproductive endocrinology and infertility. AB - OBJECTIVE: Knowledge in reproductive endocrinology and infertility is fundamental to the delivery of quality women's health care. In 1991, the American Fertility Society formed a resident education committee to gather data on the current status of reproductive endocrinology and infertility training and develop an ideal curriculum. METHODS: Program directors and reproductive endocrinology and infertility faculty from 288 residencies in obstetrics and gynecology were surveyed about training in reproductive endocrinology and infertility; 257 (89%) of the program directors (survey I) and 203 (82%) of the reproductive endocrinology and infertility faculty (survey II) responded. An ideal curriculum has been developed from consensus discussions, review of survey data, and polling of experienced educators. The curriculum was reviewed and approved by the board of directors of both the Society for Reproductive Endocrinologists and the American Fertility Society. RESULTS: The curriculum is divided into subject matter and therapeutics, which are prioritized into three levels of knowledge: critical core curriculum, less critical material, and material with which residents should have familiarity and general knowledge. In addition, other recommendations and suggestions are made regarding the number of rotations, duration of rotations, and teaching methods. CONCLUSION: The ideal curriculum may serve as a guide to assist program directors in the formulation of the most effective residency training in reproductive endocrinology and infertility. The curriculum can help prioritize what should be taught and where an emphasis can be placed. There is not enough time or resources to teach residents all aspects of reproductive endocrinology and infertility. PMID- 7784009 TI - The effects of a course in cadaver dissection on resident knowledge of pelvic anatomy: an experimental study. AB - OBJECTIVE: To determine whether a course in cadaver dissection can significantly increase resident knowledge of pelvic anatomy beyond that of current educational practices. METHODS: Thirteen first- and second-year residents were randomly assigned to a cadaver dissection course (seven) or a control group (six). The dissection group performed dissections with instruction, using a dissection guide designed specifically for the course. The control group received study references on pelvic anatomy and protected study time. Each participant took a practical and written examination at the beginning and end of the study. RESULTS: The two groups did not differ statistically in their scores on the pre-test. Both groups improved on the post-test, but the dissection group scored nearly 50% higher on the test than did the controls. The two groups differed significantly on the post test, adjusted for pre-test performance (P < .01). In their evaluation of the course, participants from the dissection group emphasized its educational value and urged that it be offered to residents as a regular part of their training. CONCLUSION: Dissection of a human cadaver provides a valuable experience, allowing participants to gain a greater understanding of surgical anatomy and surgical procedures in a no-risk, unhurried setting. Residents who participated in a cadaver dissection course designed specifically for their needs showed a statistically significant increase in knowledge compared with those without this experience. Both objectively and subjectively, a cadaver dissection course is an excellent tool for instructing gynecology residents. PMID- 7784010 TI - Perinatal implications of shoulder dystocia. AB - OBJECTIVE: To assess the antecedents of shoulder dystocia, the risk of recurrence, and the perinatal morbidity associated with the different maneuvers used for its management. METHODS: We conducted a 10-year (1980-1989) retrospective case record review of all instances of shoulder dystocia in a teaching maternity hospital. RESULTS: There were 254 cases of shoulder dystocia in 40,518 vaginal cephalic deliveries (0.6%), with 33 cases (13.0%) of brachial plexus palsy and 13 fractures (5.1%). There were no perinatal deaths attributable to shoulder dystocia. The risk of shoulder dystocia was increased with prolonged pregnancy (threefold), prolonged second stage of labor (threefold), mid-forceps deliveries (tenfold), and increasing birth weight. Of the maneuvers used to deal with shoulder dystocia, strong downward traction on the head was significantly correlated with brachial plexus palsy compared with other individual methods of delivering the shoulders. There was only one case of recurrent shoulder dystocia in 80 women having 93 cephalic vaginal deliveries after their original delivery coded with shoulder dystocia. CONCLUSION: Shoulder dystocia is not a reliably predictable event in labor. Although the risk of shoulder dystocia is increased with prolonged pregnancy, prolonged second stage of labor, increasing birth weight, and mid-forcepts delivery, the majority of cases occur without these risk factors. Strong downward traction on the head is associated with the greatest degree of neonatal trauma, whereas McRoberts maneuver has the least. The risk of recurrent shoulder dystocia is low. PMID- 7784011 TI - Development of a guidebook for senior students applying for residency training in obstetrics and gynecology. AB - This article describes a detailed residency guidebook that I developed over the course of 4 years based on interaction with 42 student advisees. Questions most frequently asked by the students were recorded, and comprehensive written responses were prepared that addressed their specific concerns. The completed guidebook contains several major sections. The introductory portion provides a general description of the discipline of obstetrics and gynecology, outlines the format of residency training programs, and assesses the competitiveness of residencies in obstetrics and gynecology compared with other disciplines. The second section lists deadlines for completing various tasks, such as selecting an adviser, planning the senior curriculum, requesting and submitting applications, preparing the curriculum vitae and personal statement, and soliciting letters of recommendation. The next section of the guidebook provides suggestions for the senior curriculum and specifically addresses the issue of "audition electives" in obstetrics and gynecology. The next two sections present formats for the student's personal statement and curriculum vitae. Next, guidelines for requesting letters of recommendation are presented. Thereafter, information is provided to help students determine the number of applications they should submit, and training programs targeted by the student are classified by size, type, and competitiveness. Finally, the guidebook addresses questions related to scheduling and preparing for interviews. PMID- 7784012 TI - Good practice with endometrial ablation. AB - OBJECTIVE: To provide clear guidelines for the safe and effective performance of endometrial ablation. DATA SOURCES: Representatives of American, Australian, British, and Canadian hysteroscopists were brought together to produce a consensus document of good practice in endometrial ablation. METHODS OF STUDY SELECTION: The guidelines were produced after researching the literature, combining the extensive experience of the group, and debating the relevant issues. CONCLUSIONS: Endometrial ablation is a new procedure. Correct patient selection is essential in producing good results. Patients must be counseled carefully about the advantages, disadvantages, and potential complications of this approach to the management of menstrual disorders. The main indication for endometrial ablation is heavy menstrual loss in the absence of organic disease. Excessive uterine size, the presence of active pelvic infection, and evidence of malignant and premalignant endometrium are absolute contraindications. Ablation can be produced by electrosurgical resection, rollerball or rollerbarrel ablation and Nd-YAG laser ablation. Severe complications can occur, and techniques should be adopted to avoid uterine perforation, hemorrhage, and excessive fluid absorption. In skilled hands, endometrial ablation can be a safe and effective treatment for menorrhagia. PMID- 7784013 TI - Cesarean delivery: a reconsideration of terminology. AB - The terminology we employ influences our perceptions. Thus, we believe in reviewing terminology regularly. The term "cesarean section" should be abandoned. A medical procedure is rarely named after a historic figure, and almost never after an ancient Roman law. Cesarean section has recently been amended to cesarean birth; however, the term is still inadequate. The word "hysterotomy" more appropriately describes the procedure we regularly perform. The adjectives used to describe cesarean birth should also be reevaluated. If we are to keep the term "classical" for the original fundal vertical uterine incision, then the other designations of hysterotomy should retain the same architectural context. Contemporary hysterotomy should be used in reference to a low transverse cesarean. Neoclassical hysterotomy might be used to describe the low vertical procedure. Transitional hysterotomy may be an appropriate term for the "hockey stick" or "J" incision. Cesarean delivery best describes a postmortem cesarean. Vaginal birth after cesarean (VBAC) is inappropriate because a vaginal birth after a cesarean section would not occur if cesarean section refers to a perimortem procedure. Vaginal birth after hysterotomy should be substituted for VBAC. Such revision of our terminology will keep obstetrics at the forefront of medical science and bring us most efficiently into the 21st century. PMID- 7784014 TI - Serious adverse events in Norplant users related to the Food and Drug Administration's MedWatch Spontaneous Reporting System. PMID- 7784015 TI - The clinical significance of a single umbilical artery as an isolated finding on prenatal ultrasound. PMID- 7784016 TI - New suturing device for laparoscopic hysterectomy. PMID- 7784017 TI - Preterm prelabor amniorrhexis: outcome of live births. AB - OBJECTIVE: To investigate the risk of postnatal death in pregnancies with preterm prelabor amniorrhexis in relation to gestational age at both amniorrhexis and delivery. METHODS: In 172 singleton pregnancies with preterm prelabor amniorrhexis resulting in live births, postnatal survival and cause of death were examined in relation to gestational age at both amniorrhexis and delivery. In 108 of the patients, the amniotic fluid index (AFI) and fetal breathing movements were determined, and in 98, the internal thoracic circumference and cardiothoracic ratio were also measured. The value of these indices in the prediction of pulmonary hypoplasia was examined. RESULTS: There were 30 (17%) deaths, 18 of which were due to pulmonary hypoplasia and 12 to prematurity related complications. Survival was related to both gestational age at amniorrhexis (50% for amniorrhexis before 20 weeks' gestation and 98% when amniorrhexis occurred after 25 weeks) and gestational age at delivery (57% for those born at 24-28 weeks' gestation and 96% for those born after 32 weeks). Pulmonary hypoplasia was also related to both gestational age at amniorrhexis (causing 92% of deaths in the group with amniorrhexis at less than 20 weeks' gestation but none of those with amniorrhexis after 23 weeks) and gestational age at delivery (causing 50% of deaths in the group delivered at 24-28 weeks' gestation and 87% of deaths in infants delivered after 28 weeks). Fetal breathing movements were present in 33 and 63% of cases with and without pulmonary hypoplasia, respectively. The corresponding values for internal thoracic circumference below the 2.5 percentile were 33 and 9%, respectively. There were no significant differences in the AFI or cardiothoracic ratio between the cases with and without pulmonary hypoplasia. Multivariate analysis demonstrated that the only characteristic that contributed significantly in distinguishing between cases with and without pulmonary hypoplasia was gestational age at amniorrhexis. CONCLUSION: In pregnancies with preterm prelabor amniorrhexis, postnatal survival is related to both gestational age at amniorrhexis and gestational age at delivery. Prediction of pulmonary hypoplasia is primarily dependent on gestational age at amniorrhexis. PMID- 7784018 TI - Bone mineral loss during lactation and recovery after weaning. AB - OBJECTIVE: To test the hypothesis that bone mineral content (BMC) and density (BMD) are lost during lactation and regained within 6 months after weaning. METHODS: Two cohorts of women, defined by time postpartum, were enrolled into the study; each cohort was followed for 6 months. Women in the lactation cohort (65 lactating women and 48 nonlactating postpartum controls) were enrolled at 2 weeks postpartum. Women in the weaning cohort (40 lactating and 43 nonlactating postpartum controls) were enrolled at 4-6 months postpartum. Lactating women enrolled in the weaning cohort had been fully breast-feeding at enrollment and weaned within 2 months of enrollment. Bone mineral content of the total body and BMD of the lumbar spine and distal radius were measured by dual-energy x-ray absorptiometry. RESULTS: Lactating women lost significantly more bone in the total body (-2.8 versus -1.7%) and lumbar spine (-3.9 versus 1.5%) than did nonlactating women during the first 6 months postpartum. There was no effect of lactation on bone changes at the distal radius. After weaning, lactating women gained significantly more bone in the lumbar spine than did nonlactating women (5.5 versus 1.8%). Earlier resumption of menses was associated with a smaller loss of bone during lactation and a greater increase of bone after weaning. CONCLUSION: Women lose bone during lactation but gain bone after weaning. Thus, lactation may not result in net bone loss. PMID- 7784019 TI - Mutational analysis of the estrogen-receptor gene in endometrial carcinoma. AB - OBJECTIVE: To determine whether mutation in the DNA of the estrogen-receptor gene occurs in endometrial cancer. METHODS: Polymerase chain reaction amplification and single-stranded conformation polymorphism analysis of the entire coding region (exons 1-8) of the human estrogen-receptor gene, as well as an untranslated region (exon I*) in the gene, were performed on genomic DNA extracted from 56 snap-frozen endometrial cancers. All cancers demonstrating mobility shifts on single-stranded conformation polymorphism suggestive of DNA sequence alteration were subjected to definitive DNA sequencing of the relevant portion of the estrogen-receptor gene. RESULTS: In addition to detecting a frequent, previously described polymorphism in exon 1, single-stranded conformation polymorphism analysis of the 56 endometrial cancers identified seven cancers with mobility shifts. Three cancers shifted in exon 3, one cancer each shifted in exons 4 and 7, and two shifted in exon 8. Deoxyribonucleic acid sequencing revealed sequence alterations in all seven cases demonstrating mobility shifts. In six of these seven cases, these alterations were consistent with infrequent silent polymorphisms; in the seventh cancer, the sequence alteration proved to be a somatic missense mutation at codon 537 in the region of the estrogen-receptor gene encoding the hormone-binding domain of the receptor protein. CONCLUSION: The infrequent DNA mutation in the estrogen-receptor gene is unlikely to account for the variation in estrogen-receptor expression observed in endometrial cancer. PMID- 7784020 TI - Comparison of D&C and office endometrial biopsy in predicting final histopathologic grade in endometrial cancer. AB - OBJECTIVE: To compare the accuracy of D&C and office Z-sampler endometrial biopsy in predicting hysterectomy tumor grade in women with endometrial cancer. METHODS: Between September 1987 and July 1994, 183 women with endometrial cancer had D&C or office Z-sampler endometrial biopsy before hysterectomy. RESULTS: One hundred thirty-one patients (72%) had Z-sampler biopsies and 52 (28%) had D&C. The Z sampler correctly identified the hysterectomy tumor grade in 76 of 131 patients (58%), compared with 40 of 52 (77%) with D&C, a significant difference (P = .024). The major difference observed was an increased fraction of lesions undergraded (ie, a lower grade tumor found in the biopsy than in the hysterectomy specimen) by the Z-sampler (34 of 131, 26%) versus D&C (five of 52, 10%). CONCLUSION: Dilation and curettage was more accurate in identifying hysterectomy tumor grade and less likely to miss a higher-grade tumor than was Z-sampler biopsy. However, the inaccuracy of D&C alone necessitates further preoperative and intraoperative assessment for other risk factors to determine the aggressiveness with which an individual patient should be staged surgically. PMID- 7784021 TI - Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. AB - OBJECTIVE: To assess the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of invasive cervical cancer. METHODS: Seventy-nine women with untreated cervical cancer underwent pre-treatment MRI (n = 71) and/or CT (n = 37) within 4 weeks of surgical evaluation. Twenty-nine women had both MRI and CT. Images were evaluated for tumor detection, size, stromal invasion, local extension, and nodal metastases. RESULTS: Tumor size was evaluated accurately by MRI, with a correlation coefficient of 0.93. Magnetic resonance estimates of tumor size were within 0.5 cm of the surgical sample in 64 of 69 women (93%). Magnetic resonance was 88% accurate evaluating the presence of stromal invasion and 78% accurate for depth of stromal invasion. Computed tomography could not evaluate tumor size or stromal invasion because it could not distinguish cancer from the surrounding normal cervical tissue. In evaluating stage of disease, MRI had an accuracy of 90%, compared with 65% for CT (P < .005). Magnetic resonance imaging was more accurate than CT (94 versus 76%, P < .005) in assessing parametrial invasion. Both modalities were comparable in evaluating lymph node metastases (86% each). In determining operative candidates (stage I and minimal IIA), MRI was 94% accurate, compared with 76% for CT (P < .005). CONCLUSION: Compared with CT, MRI offered significantly improved evaluation of tumor size, stromal invasion, and local and regional extent of disease in pre-treatment imaging for cervical cancer. PMID- 7784023 TI - Blood flow in benign ovarian tumors and normal ovaries during the follicular phase. AB - OBJECTIVE: To identify the Doppler flow characteristics of benign ovarian tumors, and to compare the variables involved with those of normal ovaries during the follicular phase. METHODS: Ninety-one women comprised the study group: 43 were recruited from patients undergoing surgical exploration because of adnexal masses, and the remaining 48 were asymptomatic volunteers with normal ovaries. The ovarian volume and morphology, location of the intratumoral and intraovarian arteries, pulsatility index (PI), resistance index (RI), peak systolic velocity, and minimum diastolic velocity were assessed with transvaginal color Doppler ultrasonography. We examined patients with adnexal tumors before surgery and asymptomatic volunteers during the follicular phase of their menstrual cycles. RESULTS: Arterial blood flow was detected in 49 (89%) of the 55 benign tumors and in 89 (94%) of the 95 normal ovaries. The PI was less than 1.0 in 80% of the benign tumors and 94% of the normal ovaries. The RI was less than 0.4 in 43% of the benign tumors and 25% of the normal ovaries. Blood flow exhibited a lower mean PI but a higher mean peak systolic velocity and minimum diastolic velocity value in benign tumors compared with normal ovaries. There were no differences in the Doppler characteristics of the benign tumors between the follicular and luteal phases. CONCLUSION: The blood flow in benign tumors and normal ovaries may have low PIs and RIs, even during the follicular phase. Therefore, low PIs and RIs alone should not be interpreted as pathognomonic signs of malignancy. PMID- 7784022 TI - Carcinoma of the vulva in young women. AB - OBJECTIVE: To determine if young women with carcinoma of the vulva have a different risk factor history and outcome compared with older women. METHODS: We conducted a retrospective review of the medical records of 78 women treated at the Medical College of Georgia for squamous carcinoma of the vulva during 1979 1993. Women younger than 45 years were compared with those 45 and over for historic risk factors, treatment modality, and outcome. RESULTS: Over the study interval, the average presenting age of these patients decreased from 69 to 55 years. Women under 45 were found to have a stronger history of condyloma (P < .001, 95% confidence interval [CI] 3.69-87.96). There was no significant difference by age in the duration of symptoms before presentation, smoking history, or tumor size. Women 45 and over were more likely to have advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV) (P = .03, 95% CI 0.43-0.91). Treatment did not differ significantly with age. In a univariate analysis, advanced FIGO stage, presence of metastases, and tumor size were associated with shorter survival. There was no detected difference in survival for women in either age group. CONCLUSION: There appears to be a trend in our patient population toward younger women presenting with squamous carcinoma of the vulva. Human papillomavirus infection appears to be more common in younger women with vulvar carcinoma. There may be a difference in the etiologies producing squamous carcinomas of the vulva. Education encouraging the early detection and prevention of sexually transmitted diseases might alter the rising incidence of this disease in younger women. PMID- 7784024 TI - Vaginal hysterectomy by uterine morcellation: an efficient, non-morbid procedure. AB - OBJECTIVE: To evaluate the relationship between uterine size and a possible increase in operative morbidity and procedure failure rates in women undergoing total vaginal hysterectomy. METHODS: A retrospective chart analysis of all hysterectomies performed for histologically confirmed leiomyomata was completed. A total of 128 cases qualified. Patients were stratified into three groups: group I, patients undergoing vaginal hysterectomy with a uterine weight of 300 g or greater but less than 1000 g; group II, patients undergoing vaginal hysterectomy with a uterine weight of 100-299 g; and group III, patients undergoing abdominal hysterectomy with a uterine weight of 100-1000 g. The variables evaluated included the following: length of hospital stay, operative time, estimated blood loss, and operative complications. Data regarding failed vaginal hysterectomy requiring an abdominal approach were also obtained. RESULTS: Both vaginal hysterectomy groups had a significantly reduced length of stay compared with the total abdominal hysterectomy group. There was no significant difference in mean estimated blood loss between groups I and III. Similarly, there were no significant differences in complication rates among the three groups. Group I had an 84% (31 of 37) success rate versus 95% (40 of 42) for group II (not statistically significant). There were no significant differences in the mean uterine weight, estimated blood loss, and complication rate in unsuccessful versus successful vaginal hysterectomies. The estimated blood loss was significantly higher for unsuccessful vaginal hysterectomy. CONCLUSION: Uterine size alone is not an absolute contra-indication to vaginal hysterectomy. Large uterine size (greater than 300 g) was not related to a significant increase in failed vaginal hysterectomy. Conversely, failed vaginal hysterectomy was not size dependent. Furthermore, there is no additional operative morbidity when vaginal hysterectomy is converted to a total abdominal hysterectomy because of a technical inability to complete the surgery vaginally. PMID- 7784025 TI - GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group. AB - OBJECTIVE: To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas. METHODS: This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater. RESULTS: Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group. CONCLUSION: Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterine-myoma volume, and in alleviating bleeding and other leiomyoma-related symptoms. PMID- 7784026 TI - Bone loss after hysterectomy with ovarian conservation. AB - OBJECTIVE: To examine the long-term effects of hysterectomy with conservation of the ovaries on bone density of the lumbar spine and proximal femur. METHODS: A cross-sectional study of the bone density of 40 postmenopausal women who had undergone hysterectomy with ovarian conservation before menopause compared with a matched group of 40 women who had not had hysterectomy. The 40 women who had undergone hysterectomy were also compared with a control population, using multiple linear regression analysis. Bone density of the femoral neck and lumbar spine was measured by quantitative digital radiography. RESULTS: Bone density in the hysterectomy group was significantly reduced at the spine (P < .05) and at the femoral neck (P < .05) compared with the matched group. Comparisons of the hysterectomy group with the reference group demonstrated that in addition to significant reductions in bone density at the spine (P < .05) and hip (P < .05), bone density at the femoral neck (P < .05), trochanter (P < .05), Ward's triangle (P < .05), and the second (P < .05) and fourth (P < .05) lumbar vertebrae was also significantly less in the hysterectomy group. CONCLUSION: Premenopausal women who have hysterectomy will have significantly lower bone density than controls, despite conservation of both ovaries at the time of surgery. PMID- 7784027 TI - Dirithromycin increases ethinyl estradiol clearance without allowing ovulation. AB - OBJECTIVE: To use a novel, sensitive study design to detect a potential oral contraceptive (OC) and dirithromycin drug interaction by assessing the pharmacokinetics of the ethinyl estradiol (E2) component of a common OC and the potential failure of OC effectiveness. METHODS: In this nonblinded study, 20 healthy women using Ortho Novum 7/7/7-28 were selected for a three-OC-cycle study. Baseline measures included E2 and progesterone serum levels on days 21, 23, 25, and 27 of cycle one and days 1, 3, 5, and 7 of cycle two. During cycle two, 24-hour blood sampling and radioimmunoassay analysis for ethinyl E2 pharmacokinetics were performed on day 8 and pelvic ultrasound on day 13. Oral dirithromycin 500 mg/day for 14 days began on day 21 of cycle 2. After starting dirithromycin, cycle two and three serum E2, progesterone, and serial ethinyl E2 levels and pelvic ultrasound replicated the baseline schedule. Ovulation was assumed if E2 concentration was greater than 50 pg/mL, progesterone concentration was greater than 3 ng/mL, or if an ovarian cyst greater than 10 mm was present on ultrasound. RESULTS: Pharmacokinetic analysis demonstrated a small (7.6%) but statistically significant decrease (P = .03) in the mean ethinyl E2 24-hour area under the curve and an increase in apparent oral clearance. No woman ovulated, based on E2 levels and progesterone concentrations or ultrasound. CONCLUSION: Dirithromycin increased the apparent oral clearance of ethinyl E2. The clinical importance of the interaction may be negligible because no woman ovulated or had compromised OC effectiveness in this small series. PMID- 7784028 TI - Evaluation of current urodynamic testing methods in the diagnosis of genuine stress incontinence. AB - OBJECTIVE: To determine the sensitivity and specificity of several urodynamic testing methods in the diagnosis of genuine stress urinary incontinence (GSI). METHODS: One hundred eight consecutive patients were evaluated prospectively by history and physical examination, cough stress test, and single and multichannel urodynamics. Sensitivities and specificities in detecting genuine stress incontinence were calculated for: a positive cough stress test with a negative cystometrogram, equalization throughout a cough urethral pressure profile, a positive stress leak-point pressure determination, observed urine loss with cough during multichannel urodynamics, and a pressure transmission ratio of less than 90% for each third of the urethra. RESULTS: Sixty-five patients (60%) were found to have GSI. Observed urine loss with cough during multichannel studies was 91% sensitive and 100% specific. A positive stress leak-point pressure determination had a 78% sensitivity and was 100% specific. A positive cough stress test with a negative cystometrogram was 77% sensitive and 100% specific. Pressure equalization throughout the length of the urethra during a cough urethral pressure profile was 49% sensitive and 98% specific. A pressure transmission ratio of less than 90% in the distal, middle, and proximal urethra had sensitivities and specificities of 54 and 79%, 51 and 65%, and 45 and 58%, respectively. A pressure transmission ratio of less than 90% along the entire length of the urethra was 22% sensitive and 93% specific. CONCLUSION: Observed urine loss with cough during multichannel urodynamics was the best examination for diagnosing GSI in our population. PMID- 7784029 TI - A randomized study to assess the efficacy of the amniotic fluid index as a fetal admission test. AB - OBJECTIVE: To determine whether there is a difference in the incidence of abdominal delivery for presumed fetal distress in women who have an intrapartum fluid index assessment and those who do not. METHODS: Over a 7-month period, parturients at 26-42 weeks' gestation and in early labor were randomized to the study (measured amniotic fluid index [AFI] on admission) or a control group (no sonographic assessment of amniotic fluid [AF] volume). The labor and delivery staff were aware of the AFI results of the study subjects. All patients had continuous electronic fetal monitoring, and none had an abnormal tracing on admission. Student t test or chi 2 was used for statistical analysis. P < .05 was considered significant. RESULTS: The study (N = 447) and control groups (N = 436) had similar maternal demographics as well as medical and obstetric complications. In the study group, the incidence of abdominal delivery for fetal distress (29 of 447) was significantly higher than among controls (14 of 436) (P = .02; relative risk 1.3, 95% confidence interval 1.1-1.7). Among parturients who had abdominal delivery for fetal distress, the decision-to-incision times (mean +/- standard deviation) were similar for parturients who had undergone assessment of AFI and those who had not (38.5 +/- 14.7 versus 32.5 +/- 14.7 minutes, respectively; P = .47). Mean birth weight, incidence of low birth weight, macrosomia, Apgar scores less than 7, and the number of admissions to the neonatal intensive care unit were not significantly different in the two groups. CONCLUSIONS: Patients having an intrapartum assessment of AFI as a fetal admission test are significantly more likely to have abdominal delivery for presumed fetal distress. However, the decision-to-incision time is not decreased and the perinatal outcome is not improved if the status of AF volume is known for patients in early labor. PMID- 7784030 TI - Long-term clinical and urodynamic evaluation of the polytetrafluoroethylene suburethral sling for treatment of genuine stress incontinence. AB - OBJECTIVE: To assess long-term clinical and urodynamic outcomes of suburethral sling procedures using polytetrafluoroethylene grafts. METHODS: Between January 1986 and May 1991, 108 women underwent suburethral sling placement to treat genuine stress incontinence. At least 1 year after surgery, 62 women participated in a telephone interview about surgical outcome and completed a follow-up urodynamic evaluation. RESULTS: Seventy-three percent of patients reported stress incontinence cure and 61% were objectively cured. Neither low urethral closure pressure nor a history of multiple prior anti-incontinence procedures, singly or in combination, adversely affected outcome. Postoperative maximum urethral closure pressure and functional urethral length were significantly greater in patients who were cured of their incontinence than in those whose surgery failed. Patients who were cured had higher amplitude detrusor contractions during micturition and greater post-void residual urine than those who were not cured. Thirty-three percent of patients with urodynamically stable bladders preoperatively developed detrusor instability after surgery. Detrusor instability remitted after surgery in half of the patients who had this condition preoperatively. Postoperative wound complications developed in 40% of patients who underwent sling placement, and 22% of the grafts were eventually removed. CONCLUSION: Polytetrafluoroethylene suburethral sling placement is an effective treatment for stress incontinence and low urethral pressure. Urodynamic data suggest that urethral obstruction is responsible for surgical cure. Patients should be warned of the high complication rate for this suburethral sling procedure and that graft removal may be necessary. PMID- 7784031 TI - Gestational diabetes mellitus: antenatal variables as predictors of postpartum glucose intolerance. AB - OBJECTIVE: To determine whether antepartum variables can predict postpartum glucose intolerance. METHODS: Glucose tolerance was assessed 6 weeks postpartum in 94 of 238 women with gestational diabetes using a 2-hour, 75-g oral glucose tolerance test (GTT). Selected antepartum variables were analyzed for predictive ability for postpartum glucose intolerance. RESULTS: Of 238 patients, 94 (39%) returned for a GTT. Those returning and those not returning were similar in all variables. Postpartum glucose intolerance occurred in 34%: impaired glucose tolerance in 18%, overt diabetes in 16%. No single maternal, intrapartum, or neonatal variable was predictive of postpartum glucose intolerance in all cases. Predictive variables included: requirement for insulin (insulin versus diet: 25 versus 3% impaired glucose tolerance, 26 versus 0% diabetes; P = .001), poor glycemic control (any 2-hour postprandial blood sugar level of 150 mg/dL or higher: 34 versus 5% diabetes; P = .005), and the 50-g GTT value (200 mg/dL or higher: 32 versus 6% diabetes; P = .01). For insulin requirement, the relative risk (RR) was 17.28 (95% confidence interval [CI] 2.46-121.45), and for the above three variables combined, the RR was 19.68 (95% CI 2.88-134.2). When the insulin dose was at least 100 U/day, all patients had abnormal glucose tolerance postpartum (RR = 34.00, 95% CI 4.93-234.39). CONCLUSIONS: Postpartum glucose screening is not warranted for women at low risk who do not require insulin during pregnancy. The incidence of postpartum glucose intolerance in this group is very low. Women with risk factors should receive postpartum screening. Patients receiving at least 100 U/day of insulin have a 100% incidence of postpartum glucose intolerance. PMID- 7784032 TI - Management of anesthetic complications and emergencies in the obstetric patient. AB - The importance of cooperation and understanding between the obstetrician and anesthesiologist in the management of obstetric emergencies cannot be overemphasized. Indications for cesarean section and choice of anesthetic are significant considerations. Algorithms for the management of special treatment problems such as malignant hyperthermia, postdural headache, and epidural abscess and hematoma are presented. Posting of protocols for the management of particular crises in both delivery and postanesthesia care units is strongly recommended. PMID- 7784033 TI - Acute hypotension related to hemorrhage in the obstetric patient. AB - Acute hypotension in the setting of hemorrhage most often signifies abrupt and dangerous blood loss. The physiologic changes of pregnancy are designed to protect the mother from blood loss at parturition. When this protective reserve is exceeded, hypovolemic shock occurs. Ideally, blood loss of this magnitude should not be allowed to occur. Notwithstanding, obstetric hemorrhage continues to be an important cause of maternal mortality. Most deaths due to hemorrhage are preventable. Successful treatment requires that the clinician must react with the immediate institution of effective resuscitative measures. The importance of an organized, team approach with input from relevant specialties in the scheme of management cannot be overemphasized. PMID- 7784034 TI - The antepartum patient. Sudden changes in central nervous system status and sensorium. AB - An approach to the pregnant patient with altered consciousness is presented. The unconscious pregnant patient often represents a straightforward simple problem if the event is a minor syncope secondary to physiologic changes of pregnancy. Most loss of consciousness is postictal in nature after either an epileptic or eclamptic seizure. If these are ruled out, other more serious causes must be considered, and the patient must be fully evaluated by appropriate neurologic consultants. PMID- 7784035 TI - Management of drug dependency, overdose, and withdrawal in the obstetric patient. AB - This article discusses the approach to pregnant patients with substance use problems, a growing problem in obstetric practice. Two alternatives used to detect patients with problematic substance use are discussed: (1) historic screening, which depends on the patient to self-report about her substance use; and (2) toxological assays for substances or their metabolites in the patients' body fluids. Management of women using cocaine and alcohol is also discussed. PMID- 7784036 TI - Management of diabetic ketoacidosis in the obstetric patient. AB - Because of the normal metabolic changes found in pregnancy, diabetics are at increased risk to develop ketoacidosis. Even though the incidence of DKA during pregnancy has declined in recent years, prompt recognition of the presenting signs and symptoms followed by appropriate treatment of the associated metabolic disturbances can be lifesaving to the mother and her unborn child. Therapy is directed toward aggressive fluid resuscitation, avoidance of hypokalemia, and reversal of the hyperglycemia and ketoacidosis. When the clinician is confronted with DKA in the obstetric patient, aggressive therapeutic measures should maximize maternal and fetal outcome. PMID- 7784037 TI - New-onset hypertension in the pregnant patient. AB - The new onset of hypertension in pregnancy most often reflects preeclampsia, underlying chronic hypertension, chronic hypertension with superimposed preeclampsia, or gestational hypertension, and less commonly is due to substance abuse or any of several rare conditions. The term "pregnancy-induced hypertension" applies to all of these categories, but because it does not adequately and specifically define the patient's condition, its use therefore is discouraged. Attention to accurate identification of the specific type of "pregnancy-induced hypertension" is important since treatment varies depending on the diagnosis and the stage of pregnancy from observation with gestational hypertension to active intervention in the patient with chronic hypertension and superimposed preeclampsia. Both perinatal and maternal outcomes are dependent also on the categorization of the hypertensive disorders of pregnancy. Efforts to selectively identify, correctly diagnose, and optimally treat each hypertensive mother should help to achieve the best possible outcome with the least maternal risk. PMID- 7784038 TI - Sudden joint and extremity pain in pregnancy. AB - To diagnosis sudden joint and extremity pain in pregnancy, the obstetrician must call upon information from several disciplines, including obstetrics, internal medicine, neurology, and orthopedics. The initial evaluation of the patient should begin with a generalized assessment, and more distant causes of the pain should be ruled out as possible causes are considered, evaluated, and rejected. This article discusses the importance of medical history, physical examination, laboratory studies, synovial fluid analysis, and immunologic studies to aid in the diagnosis of pain, as well as common presentations of musculoskeletal pain in pregnancy. PMID- 7784039 TI - Sudden chest pain and cardiac emergencies in the obstetric patient. AB - The differential diagnosis and work-up of a patient with chest pain during pregnancy is presented in this article. This is followed by discussions of cardiac emergencies including hypertensive crisis, pulmonary edema, arrhythmias, cardiopulmonary resuscitation, myocardial infarction, and aortic dissection. PMID- 7784040 TI - Acute pulmonary dysfunction and distress. AB - Acute pulmonary dysfunction and distress is not uncommon in the obstetric patient. In these situations, however, a quick assessment and intervention is necessary in many cases. This article familiarizes the practicing obstetrician with the physiology and therapy to evaluate and effectively treat these patients. PMID- 7784041 TI - Acute abdominal pain in pregnancy. AB - The anatomic and physiologic changes of pregnancy make the diagnosis and management of abdominal pain difficult. Abdominal conditions both related and unrelated to the pregnancy may be life threatening for mother or fetus; therefore, accurate diagnosis and proper management are essential. This article reviews the most common conditions presenting as acute abdominal pain during pregnancy. PMID- 7784042 TI - Management of moderate to severe trauma in pregnancy. AB - Severe trauma to an obstetric patient is truly an injury of double magnitude. While being cognizant of the fetus and its well-being, all expediency must be employed to accomplish a thorough evaluation of the injured patient and allow for the prompt employment of appropriate therapeutic measures. The best key to fetal survival is successful maternal therapy. PMID- 7784043 TI - Acute hypotension related to sepsis in the obstetric patient. AB - While infections are a common complication of pregnancy, bacteremia and septic shock are relatively rare. Efforts to prevent serious bacterial infections are the most effective means of minimizing maternal and fetal morbidity. Screening for first trimester asymptomatic bacteriuria, prompt and thorough evaluation of suspected bacterial infections, and conscientious intrapartum assessment can have a significant impact in decreasing localized bacterial infections. The prompt recognition and institution of antimicrobial therapy in women suspected of having systemic infections is of paramount importance in reducing the incidence of serious maternal morbidity and mortality. Initial efforts in the treatment of sepsis should be directed at intravascular volume expansion in an effort to improve myocardial performance and tissue oxygenation. Inotropic agents occasionally may be necessary; however, they should be used with caution and only after adequate volume expansion has been provided. Adequate antimicrobial therapy requires treatment with multiagent therapy, providing coverage for the wide variety of genital tract pathogens. PMID- 7784044 TI - [Surgical management of acute and chronic arterial occlusion]. AB - Arterial occlusion may develop acutely and chronically, can affect any artery in the body. Surgical treatment of the disease is reasonable when definite symptoms occur. The forms of surgical treatment are: in acute arterial occlusion embolectomy or thrombectomy with Fogarty balloon catheter, under special circumstances in this group of patients we are compelled to use the typical surgical technique for chronic occlusion; the bypass and thrombendarteriectomy. Reconstructive operations are made most often on the lower extremities: thrombendarteriectomy or artificial prosthetic grafting on the aortoiliac section, autogenous saphenous vein bypass on the femoropopliteal section, and this is also the recommended procedure in the cases when the occlusive disease affects the crural arteries. Other operations in connection with occlusive arterial disease are lumbal and thoracal sympathectomy, fasciotomy and amputation at different levels. The recognition of occlusive disease on the extracranial carotid arteries are getting more and more common nowadays. The recommended operation in carotid occlusive disease is eversio endarteriectomy. Compared with the above the reconstructive operations of the mesenterial and renal arteries are rare. In the cases we do operate the operations are seldomly thrombendarteriectomies and more often bypasses with autogenous saphenous vein or artificial prosthetic grafts. PMID- 7784045 TI - [Growth hormone therapy in adults]. AB - GH deficiency in adults is associated with decreased lean body mass and increased adiposity. Since body composition changes in the elderly are similar to those of GH deficiency and can be partially reversed by hGH replacement, it has been postulated that the diminished GH secretion in the later years of life may contribute to the geriatric changes in body composition. GH treatment of GH deficient adults or old men increases nitrogen retention, lean body mass, decreases percent of body fat. Clinical trials have shown beneficial effects of hGH in several disorders associated with protein catabolism. The short-term adverse effects of GH therapy have been minimized by using low-dose regimens. GH treatment is justified to certain elderly patients, such as those suffering mainly from catabolic illnesses, malnourishment, burns, cachexia, and can be considered in GH-deficient adults. PMID- 7784046 TI - [Early stage gastric cancer in Vas County]. AB - Between 1983 and 1992, 44 patients with early gastric cancer underwent operative treatment. This group comprised 13.3 percent of all patients with gastric cancer operated on during this period. Every patient underwent oesophago-gastro duodenoscopy before operation. The indication for surgery was histologically confirmed carcinoma in 37 patients, gastric haemorrhage in 2 patients and gastric ulcer unresponsive to medical treatment in 5 patients. The gastric carcinoma was limited to the mucosa in 28 cases and involved the submucosa in 16. Five patients, one with mucosal and four with submucosal early gastric cancer had regional metastatic lymph node involvement. Life-table calculated patient survival rate at 5 years, excluding the perioperative mortality, was 79.4 percent. CONCLUSIONS: 1. The prevalence of early gastric cancer proved to be similar to previously published in West-Europe and United States. 2. If early gastric cancer is limited only to the mucosa, regional metastatic lymph node is relatively rare. 3. Gastrointestinal bleeding can be the first clinical sign of early gastric cancer. 4. Therapy resistant gastric ulcer requires surgery irrespective of the histological examination of the biopsy specimen. PMID- 7784047 TI - [Use of a stoma-pouch after temporary pharyngostoma and neck fistula following surgery in the head and neck region]. AB - The authors report on a new way of stoma care that to their best knowledge has not been used yet in head and neck surgery patients. Their cases demonstrate the usefulness of this method for the rehabilitation of patients with pharyngeal stoma of any origin. PMID- 7784048 TI - [Simultaneous occurrence of ulcerative colitis and psoriasis in childhood]. AB - Authors report of a 10 years old girl who at age 2 showed signs of psoriasis and after 8 years typical symptoms of ulcerative colitis manifested. In connection with this case the association of two diseases is emphasized which may be explained by the similarity of genetic and immunological factors in both disorder. It is accentuated that at the observation of enteral symptoms in patients with psoriasis the possibility of non specific inflammatory bowel disease has also to be considered. PMID- 7784049 TI - [Possibilities of conservative treatment of childhood vesicoureteral reflux]. PMID- 7784050 TI - [Possibilities of conservative therapy of childhood vesicoureteral reflux (discussion)]. PMID- 7784052 TI - The pRb-related protein p130 is a possible effector of transforming growth factor beta 1 induced cell cycle arrest in keratinocytes. AB - Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit epithelial cell growth by inducing a G1 cell cycle arrest. We have studied the effect of TGF beta 1 on protein binding to a transcription factor E2F consensus element in extracts from early passage human keratinocytes (HFKs) and a permanent human keratinocyte cell line (HaCaT). Treatment of these cells with TGF-beta 1 resulted in the formation of a DNA binding complex between the pRb-related protein p130 and E2F. Formation of the E2F-p130 complex correlated with inhibition of cell cycle progression in G1 and suppression of the E2F-regulated cdc2 gene. While p130 mRNA and protein levels were not influenced by TGF-beta 1, the activity of cyclin-dependent kinase 2 (Cdk2) towards p130 in vitro was inhibited. The results identify p130 as a downstream target of TGF-beta 1 and a possible mediator of the G1 cell cycle arrest. PMID- 7784051 TI - A complex between E2F and the pRb-related protein p130 is specifically targeted by the simian virus 40 large T antigen during cell transformation. AB - The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation. PMID- 7784053 TI - Cloning and characterization of human DP2, a novel dimerization partner of E2F. AB - The transcription factor E2F consists of a family of proteins that bind to the sequence TTTCGCGC and regulate the expression of various cellular and viral promoters. E2F binds to DNA as homodimers or as heterodimers in association with a protein, DP1 (for dimerization partner 1). E2F-DP1 heterodimers bind more efficiently than homodimers to DNA, retinoblastoma gene product as well as the adenovirus E4 protein and DP1 can stimulate transcription from E2F sites in a synergistic fashion. Here we describe the cloning and characterization of a novel human DP gene, DP2, whose product dimerizes efficiently with E2F. Unlike DP1, there appear to be multiple transcripts for DP2 and their distribution appears to vary in different tissues and cell lines. DP2 binds to E2F as detected by in vitro reconstitution assays and an E2F-DP2 heterodimer can bind to DNA in gel retardation assays. We believe that DP2 also plays a major role in modulating the function of E2F in cell cycle regulation and oncogenesis. PMID- 7784054 TI - Raf phosphorylates p53 in vitro and potentiates p53-dependent transcriptional transactivation in vivo. AB - Using recombinant baculovirus expressed p53 and Raf proteins, we show that activated Raf-1 kinase can phosphorylate mouse p53 in vitro. We also show that co expression of vRaf and p53 in NIH3T3 fibroblasts, potentiates the ability of p53 to transactivate a minimal promoter with a p53 cognate DNA binding site. A dominant negative mutant of Raf inhibits the transactivation function of p53 in NIH3T3 fibroblasts. Incubation of Raf-1 kinase with a series of p53 derived synthetic peptides maps the Raf-1 phosphorylation sites to the 27 amino terminal residue region of p53 which coincides with the transactivation domain. Phosphorylation occurs on serines which are phosphorylated in vivo. Our results suggest that the transactivation function of p53 can be regulated by a signaling cascade involving Raf. PMID- 7784055 TI - Effects of p53 mutants on wild-type p53-mediated transactivation are cell type dependent. AB - The spectrum of p53 mutations differs among human cancer types. We have hypothesized that the p53 mutational spectrum observed in particular tumor types reflects the functional ability of different p53 mutants to modulate wild-type (WT) p53-dependent gene transcription. Missense p53 mutants representing several mutational hotspot codons were cotransfected with WT p53 and analysed for their effects on p53-dependent transactivation of a reporter construct containing a specific p53 binding sequence (PG13-CAT) in human tumor cell lines lacking endogenous p53. Our results show that the ability of p53 mutants to inhibit WT p53-mediated transactivation is cell type dependent. In cell lines derived from a lung adenocarcinoma and a mesothelioma, the transactivation function of WT p53 was strongly inhibited by all p53 mutants examined. However, in cell lines derived from a prostate carcinoma and an osteosarcoma, the mutants examined generally had only minimal dominant negative effects. In cell lines derived from a hepatocellular carcinoma and an ovarian carcinoma, two mutants (248trp and 273his) enhanced WT p53-mediated transactivation of the reporter construct. Additional mutants retained the ability to inhibit WT p53-mediated transactivation in these cell lines. In addition, in a series of four breast tumor cell lines, the p53 mutants examined had similar effects on WT p53 transactivation ability including enhanced transactivation activity in the 273his cotransfectants. The p53 mutants were incapable of transactivating the PG13-CAT reporter in the absence of WT p53 expression. Therefore, the dominant negative effects of p53 mutants on WT p53 function may vary depending on the particular cell type. In addition, mutants with stronger inhibitory capabilities may confer a selective advantage during the tumorigenic process. PMID- 7784056 TI - Signalling pathways involved in the mitogenic action of lysophosphatidylinositol. AB - Lysophosphatidylinositol has been previously shown to stimulate cell proliferation in differentiated and in K-ras transformed thyroid cells. Increased levels of lysophosphatidylinositol, but not lysophosphatidylcholine or lysophosphatidylethanolamine, are present in thyroid as well as in other ras transformed cell lines. We have now investigated the mechanism of action of this lysolipid by analysing its effects in a differentiated thyroid cell line. Lysophosphatidylinositol did not increase the levels of cAMP, the main stimulator of cell proliferation in the thyroid, whereas it stimulated phosphoinositide breakdown, mobilization of cytosolic Ca2+ and arachidonic acid release, suggesting that it activates both phospholipases C and A2. None of the effects of lysophosphatidylinositol were prevented by pretreatment of cells with pertussis toxin. Instead, the tyrosine kinase inhibitors, tyrphostins AG18 and AG561, completely blocked its mitogenic action. The effects of lysophosphatidylinositol were distinguishable from those of the well known mitogen lysophosphatidic acid, which affected differently the signalling pathways analysed and was not mitogenic in ras-transformed cells. These results suggest that the mitogenic activity of lysophosphatidylinositol is associated with the activation of phospholipase C and phospholipase A2 and is relatively specific for ras-transformed cells. PMID- 7784057 TI - Cyclin D2 is a moderately oscillating nucleoprotein required for G1 phase progression in specific cell types. AB - To explore regulation and function of cyclin D2, a candidate cell cycle regulatory proto-oncogene, we examined subcellular localisation, cell type- and cell cycle-dependent expression, and requirement of cyclin D2 protein for G1 progression, in a panel of 40 human normal and cancer cell types. Except for lymphoid cells and sarcoma cell lines, expression of cyclin D2 was considerably more restricted than that of cyclin D1, whereas both D-type cyclin proteins were low or undetectable in cells lacking functional retinoblastoma gene product. In G1 cells, the cyclin D2 protein was more resistant to extraction and localised predominantly to nuclei, whereas it became more soluble and distributed in both nuclei and cytoplasm from G1/S transition onwards. Centrifugal elutriation and multiparameter flow cytometry analyses of several cell types showed moderate cell cycle oscillation with maximum levels of the cyclin D2 protein reached in late G1. Microinjection and/or electroporation of antibodies to cyclin D2 during G1 arrested the cyclin D2-expressing lymphocytes, breast myoepithelium, and U-2-OS sarcoma cells in G1 phase, whereas cyclin D2-negative cell types were unaffected by such treatment. Consistent with the putative proto-oncogenic role of cyclin D2 in specific cell types, our data show that this G1 cyclin has properties closely resembling those of cyclin D1, including the essential positive role in regulation of G1. PMID- 7784059 TI - Wild-type p53 down-regulates transcription from oncogenic human papillomavirus promoters through the epithelial specific enhancer. AB - High-risk Human Papillomavirus (HPV) E6 and E7 immortalizing oncoproteins are expressed from a promoter tightly regulated by an epithelial specific enhancer. To determine if the p53 tumour suppressor protein can modulate the transcription of these genes, we performed co-transfection experiments with plasmids containing the HPV type 16 or 18 long control regions linked to the chloramphenicol acetyl transferase gene, along with p53 expression vectors. Wild-type, but not mutant, murine or human p53 expression vectors reduced the activity of reporter constructs when co-transfected into HeLa or C33 cell lines. Mutations within the HPV TATA boxes did not significantly alter the levels of p53 repression, suggesting a TATA-independent mechanism. Deletion analyses mapped the p53 responsive domain to the constitutive 230 base pair epithelial specific enhancer. In addition, the enhancer could confer p53-mediated repression when placed upstream of a heterologous promoter. PMID- 7784058 TI - Combined oral carcinogenicity of HPV-16 and benzo(a)pyrene: an in vitro multistep carcinogenesis model. AB - We previously immortalized normal human oral keratinocytes by transfection with recombinant HPV-16 DNA and subsequently exposed the cells to benzo(a)pyrene for 7 days. The exposure to benzo(a)pyrene modified the immortalized cells: the modified cells (HOK-16B-BaP) proliferated in an ordinary culture medium containing physiological calcium level (1.5 mM), but demonstrated only enhanced proliferation capacity without tumor formation in nude mice and failed to show in vitro anchorage-independency. In this study, we further modified the HOK-16B-BaP cells by subculturing the cells in a medium containing benzo(a)pyrene for 6 months. The cells were further modified with a chronic benzo(a)pyrene exposure and were termed HOK-16B-BaP-T cells (1) demonstrated a malignant phenotype in organotypic 'raft' culture, (2) showed in vitro anchorage-independency, (3) developed tumors in nude mice when injected subcutaneously, (4) contained a significantly higher copy number of intact and integrated HPV-16 DNA; (5) contained higher level of HPV-16 E6/E7 messages and E7 protein, (6) were more resistant to transforming growth factor-beta 1 and (7) secreted higher level of vascular endothelial growth factor with molecular weight of 56 kd than parental HOK-16B-BaP cells. However, the levels of p53 and ras proteins and the levels of p53, c-myc and c-fos transcripts in the HOK-16B-BaP-T cells were not different from those in the HOK-16B-BaP cells. The highly conserved coding regions of the p53, c-Ha-ras1, and c-Ki-ras2 genes of the tumor cells were not mutated. These data indicate that the HPV-immortalized human oral keratinocytes can convert to tumorigenic cells by chronic exposure to benzo(a)pyrene. The tumorigenic conversion seems to be associated with (1) the overexpression of viral oncogenes such as E6 and E7 genes, (2) the higher resistance of cells to transforming growth factor-beta 1 and (3) the high secretion of 56 kd vascular endothelial growth factor from the cells. PMID- 7784060 TI - Expression of antisense osteopontin RNA inhibits tumor promoter-induced neoplastic transformation of mouse JB6 epidermal cells. AB - Elevated expression of osteopontin (OPN), a secreted adhesive phosphoglycoprotein, is frequently associated with many transformed cell lines of epithelial and stromal origin. Moreover, several clonal lines of preneoplastic JB6 cells derived from Balb/c mouse epidermal cultures (Colburn et al., 1978, 1979), upon treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), become irreversibly oncogenic and concomitantly synthesize OPN at elevated levels (Smith and Denhardt, 1989). In the present study we sought to determine whether OPN expression facilitates transformation of such preneoplastic (initiated) cells. We transfected TPA-promotable JB6 c141.5a cells with an expression vector containing mouse OPN cDNA in antisense orientation under transcriptional control of dexamethasone-inducible MMTV-LTR promoter. Four stably transfected clones, which expressed drastically reduced levels of OPN in the presence of both dexamethasone and TPA, were characterized. We found that (a) more than 20 copies of OPN antisense cDNA were stably incorporated into the genome of cells from two of these clones that were examined by Southern blot analysis; (b) dexamethasone induced expression of antisense OPN RNA prevented augmented OPN expression at both mRNA and protein levels following TPA treatment; and (c) cells from all four clones failed to form colonies in soft agar medium containing both dexamethasone and TPA. Taken together, these data demonstrate that inhibition of elevated OPN expression blocks TPA-induced anchorage-independent growth of JB6 c141.5a cells, suggesting the possibility that OPN overproduction is causally related to transformation of preneoplastic cells. PMID- 7784061 TI - TTF, a gene encoding a novel small G protein, fuses to the lymphoma-associated LAZ3 gene by t(3;4) chromosomal translocation. AB - We have previously shown that the LAZ3/BCL6 gene encoding a potential transcription factor, is disrupted in B-diffuse large cell non-Hodgkin's lymphomas (NHL) with 3q27 chromosomal abnormalities involving the immunoglobulin (IG) genes. However, LAZ3 rearrangement also occurs in NHL bearing 3q27 translocations without involvement of the IG genes: for example the VAl cell line exhibits t(3;4)(q27;p11). In the present work we have used a RT-PCR method to detect and to sequence the LAZ3 mRNA products from the VAL cell line. We report that the consequence of the t(3;4) is the expression of a chimeric transcript of LAZ3 with a new gene encoding a small G-like protein, termed TTF (Translocation Three Four). Nucleotide sequence analysis of a 1.4 kb cDNA predicts that the TTF gene encodes a protein of 191 amino-acids similar to members of the RAS superfamily including HRAS (27% identical), RAB1A (30% identical) and RHO proteins: the human RAC1, RHOB and CDC42Hs proteins (respectively 43, 44 and 45% identical) and the yeast RHO2 protein (44% identical). Unlike most other small G proteins which are expressed ubiquitously, TTF was transcribed only in hemopoietic cells as a 2.2 kb transcript. TTF may define a new subgroup of RHO like proteins. PMID- 7784063 TI - Identification of the promoter of the human von Hippel-Lindau disease tumor suppressor gene. AB - The von Hippel-Lindau (VHL) disease gene is a novel multiple tumor suppressor gene which plays a causal role in the origin of some common cancers including clear cell renal carcinomas and hemangioblastomas of the central nervous system. Here we report the identification of transcription start sites and the promoter of the human VHL gene. The promoter sequence does not contain TATA and CCAAT boxes. Transcription is initiated around a putative SP1 binding site about 60 bp upstream from the first AUG codon in the VHL mRNA. Several putative transcription factor binding sites, notably for nuclear respiratory factor 1 and PAX, were found upstream of the transcription start sites. Promoter-luciferase expression constructs demonstrate, that the promoter is functional when transfected into 293 cells (transformed primary human embryonal kidney cells) and UMRC 6 renal carcinoma cells. Activity is dependent on correct orientation of the promoter. A minimal promoter region of 106 bp was delineated. A set of VHL minigenes, containing the 5' flanking VHL genomic region, was constructed and transfected into UMRC 6 cells. In these cells the level of transcription from the minigenes driven by VHL promoter was comparable with endogenous VHL expression. PMID- 7784062 TI - Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. AB - The murine Unp proto-oncogene encodes a nuclear ubiquitin protease whose overexpression leads to oncogenic transformation of NIH3T3 cells. We have cloned cDNAs originating from the human homolog of this gene, designated herein as Unph (Unp, human), and have used these cDNAs to map the gene to 3p21.3, a region frequently rearranged in human tumor cells. Unph mRNA levels are consistently elevated in small cell tumors and adenocarcinomas of the lung, suggesting a possible causative role for the gene in the neoplastic process. PMID- 7784064 TI - Specific c-myc and max regulation in epithelial cells. AB - We have investigated c-myc, max and c-fos mRNA and protein expression in proliferating, quiescent and stimulated immortalized, SV40 T antigen (LT) transformed and tumor-derived epithelial cells as well in human primary keratinocytes and have compared them to their expression in fibroblasts. In proliferating immortalized and tumor-derived epithelial cells, the levels of c myc, max and c-fos expression were comparable and much higher than in transformed fibroblasts. c-myc and c-fos mRNA and protein levels remained high even during quiescence, when cells stopped dividing. In contrast, whereas max mRNA was constitutively expressed, max protein levels decreased in both fibroblasts and epithelial cells at high cell density. Changing the medium to serum-free medium of confluent epithelial cells induced a complete proliferative response which started with a transient increase in c-fos and c-myc mRNA, followed by the expression of max. Addition of serum to the medium did not induce additional effects. In fibroblasts, similar treatment induced the arrest of c-myc expression and growth, but max expression was also induced in these cells by serum. Our results therefore show that max expression is growth regulated in both immortalized and transformed epithelial as well as fibroblast cells. In contrast, in epithelial cells, c-myc displayed two contrasting behaviors. PMID- 7784066 TI - Overexpression of PKC zeta in NIH3T3 cells does not induce cell transformation nor tumorigenicity and does not alter NF kappa B activity. AB - Signal transduction is the major mechanism by which cells communicate among themselves through extracellular stimuli. Among the different structural components involved in signal transduction, protein kinases are one of the key elements in the process. Protein kinase C is a multimember family of kinases which has been involved in the regulation of diverse cellular functions. Regulation of cell growth in fibroblasts has been reported to be one of such functions. In particular the PKC zeta isoenzyme has been postulated to be transforming to NIH3T3 cells (Berra et al., 1993) and to serve as an effector for Ras proteins through the regulation of the NF kappa B transcription factor (Dominguez et al., 1993) and direct interaction (Diaz-Meco et al., 1994). We have investigated the effects of overexpressing the mouse wild-type PKC zeta in NIH3T3 cells. When compared to the parental NIH3T3 cells, we have found (1) no significant effect on cell morphology; (2) no difference in growth properties in the absence of serum or in the presence of individual growth factors such as insulin, phorbol esters or PDGF; (3) no growth in soft agar nor tumorigenic activity in nude mice. In addition cells stably overexpressing the PKC zeta kinase did not interfere or amplify the induction of NF kappa B activity by tumor necrosis factor alfa (TNF-alpha) nor altered NF kappa B activity in transient expression of cells treated with TNF-alpha. Thus, mammalian PKC zeta is most likely not directly involved in the regulation of cell proliferation in fibroblasts nor affects directly or indirectly the activation of NF kappa B. PMID- 7784065 TI - Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells. AB - Interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM CSF) induce DNA synthesis and suppress apoptosis of hematopoietic cells. IL-3/GM CSF exert pleiotropic functions by activating multiple signaling cascades through distinct domains of the common receptor subunit. As we previously reported, the Ras signaling pathway plays a pivotal role in suppressing apoptotic death rather than stimulating DNA synthesis in IL-3 dependent hematopoietic cells. In order to clarify the molecular basis of Ras-induced cell survival, we investigated the effect of Ras activation on the expression of Bcl-2 and its related molecules. Activation of the Ras pathway by using an inducible oncogenic Ras resulted in the rapid up-regulation of bcl-2 and bcl-xL, and the level of expression was nearly equivalent to that observed in growing cells. On the other hand, expression of bax, an antagonistic bcl-2 homologue, was not affected by oncogenic Ras or IL-3 deprivation. Thus, the Ras pathway regulates the expression of Bcl-2 and its related survival protein, and this appears to underlie the mechanism by which IL 3/GM-CSF inhibit apoptosis through activation of the Ras pathway. PMID- 7784067 TI - High affinity DNA binding of native full length c-Myb and differential proteolytic sensitivity of its N- and C-terminal domains. AB - c-Myb is the prototype of a family of transcription factors characterised by a unique DNA binding domain. Previous analyses have concentrated on truncated versions of c-Myb as it has been very difficult to produce full length c-Myb. To overcome these difficulties we expressed full length c-Myb in HeLa cells using a recombinant vaccinia virus. Partially purified native full length c-Myb bound efficiently and specifically to DNA with a dissociation constant similar to that obtained with bacterially expressed DNA binding domains. No evidence was found for a negative effect of the leucine zipper on DNA binding. Furthermore the DNA binding domain was protease resistant in contrast to the transactivation and negative regulatory domains. Phosphorylation had no apparent effect on this differential protease sensitivity. The increased sensitivity of the C-terminal domain suggests a more open conformation, which may be relevant in the integration of signals and/or in protein-protein interactions. PMID- 7784068 TI - A transactivator of c-myc is coordinately regulated with the proto-oncogene during cellular growth. AB - A recently cloned nuclear protein, which binds a far upstream element (FUSE) of the human c-myc proto-oncogene, stimulates promoter driven expression in undifferentiated cells. In concert with a loss of c-myc expression, both FUSE binding protein (FBP) mRNA and protein levels disappeared in HL60 cells after PMA induced differentiation, due to a drop in the rate of transcription that was measured by nuclear runoff. During the differentiation of these cells, the brief half-lives of FBP mRNA (3 h) and protein (1.5 h) did not change, allowing for the rapid down-regulation of nuclear protein levels, as detected by immunohistochemical staining. Like c-myc, FBP is expressed in proliferating cells from a variety of lineages, but not in quiescent cells. When T cells and fibroblasts were stimulated to transit from G0 into the cell cycle, there was a dramatic rise of both FBP mRNA and DNA sequence specific nuclear FBP binding activity, which correlated with the appearance of c-myc mRNA. In contrast to the transient expression of many other immediate early growth response genes, both FBP and c-myc expression were sustained for more than 24 h. In fibroblasts, the coordinate expression of FBP and c-myc throughout all phases of the cell cycle is consistent with FBP's role as a growth-dependent regulator of c-myc expression. PMID- 7784069 TI - Identification of alternative exons, including a novel exon, in the tyrosine kinase receptor gene Etk2/tyro3 that explain differences in 5' cDNA sequences. AB - Protein tyrosine kinase transmembrane receptors trigger signal transduction cascades upon ligand binding, resulting in cellular proliferation, differentiation, differentiation inhibition or apoptosis depending upon the cell target. The ETK2/TYRO3 receptor is a tyrosine kinase expressed in embryonic stem cells, brain and testis that has recently been cloned by several groups. Analysis of cDNA clones isolated from several tissues shows 2 isoforms of the Etk2/tyro3 gene product that result from usage of alternative exons near the 5' end of the gene. In addition, our data suggest that a third alternative exon is positioned between these two alternative exons. This novel exon encodes yet another isoform that predicts a unique amino-terminal protein sequence. The alternative exons (exons 2A, 2B and 2C), predict three isoforms with different initiation codons, signal sequences and lengths. The existence of these multiple isoforms may be important for protein processing, translocation, or function. PMID- 7784070 TI - Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25. AB - The high incidence of loss of chromosome 10 alleles in glioblastoma multiforme suggests the presence on this chromosome of a tumor suppressor gene that is important in glioma tumorigenesis and progression. Our initial deletion mapping studies using restriction fragment length polymorphism markers indicated a common deletion region in 10q24-qter. In an attempt to localize the deleted region further, we screened a panel of 117 gliomas for loss of heterozygosity for chromosome 10 loci using 10 microsatellite markers. Seventeen tumors showed partial loss of a copy of chromosome 10 and were further analysed using 28 additional microsatellite markers. Of these, 10 had terminal deletion in the q arm, three had deletions in both p and q arms, two contained interstitial deletion in 10q and two carried deletions in 10p. In the 15 tumors with deletions in 10q, the minimal overlapping deletion region was in distal 10q between markers D10S587 and D10S216. Loci D10S587 and D10S216 are approximately mapped to a 5 cM region in 10q25.1. PMID- 7784071 TI - v-Src-induced degradation of focal adhesion kinase during morphological transformation of chicken embryo fibroblasts. AB - Morphological transformation of cells by the v-Src tyrosine kinase is incompletely understood. However, it is independent of nuclear functions and probably involves phosphorylation of targets associated with the cytoskeleton and focal adhesions, structures which tether the cytoskeleton to the points of cell attachment. v-Src activity both stimulates tyrosine phosphorylation of a tyrosine kinase present in focal adhesions (focal adhesion kinase or pp125FAK) and disrupts focal adhesions, leading to cell rounding and detachment. However, pp125FAK is also phosphorylated on tyrosine as a result of integrin stimulation which induces quite different biological consequences including the organisation of focal adhesions when cells spread on fibronectin (reviewed in Schaller and Parsons, 1993). To address this paradox, we examined changes in pp125FAK during activation and shut-off of temperature sensitive mutant v-Src proteins that induce varying degrees of transformation in chick embryo fibroblasts. An efficiently transforming v-Src mutant initially stimulated pp125FAK tyrosine phosphorylation, but induced subsequent pp125FAK degradation prior to the onset of cell rounding and detachment. v-Src mutants which are impaired in their ability to induce morphological transformation were much less efficient at inducing degradation of pp125FAK. Moreover, cell spreading during restitution of normal morphology did not require detectable tyrosine phosphorylation of pp125FAK, or its potential substrate paxillin, suggesting that pp125FAK may function more in the turnover of focal adhesions than in their assembly. PMID- 7784072 TI - Co-regulated expression of dbl and poly(ADP-ribose) polymerase in Ewing's sarcoma cells and dbl-transformed NIH3T3 fibroblasts. AB - Poly(ADP-ribose) polymerase (PADPRP) is a ubiquitous enzyme constitutively expressed at low levels in the majority of eukaryotic cells, including most mammalian tumors and tumor-derived cell lines. Overexpression of PADPRP following the introduction of cDNA recombinant constructs into various cell types results in cell death. An exception to this effect are Ewing's sarcoma (ES) cells, which have been shown to contain elevated steady-state levels of PADPRP mRNA and high constitutive levels of protein and polymerase activity. In fact, this excess of PADPRP has been suggested to participate in the intrinsic radiosensitivity of Ewing's sarcomas, a highly malignant childhood bone tumor frequently curable with radiotherapy. It appears that ES cells might possess a hitherto unknown mechanism(s) by which PADPRP overexpression is controlled and made compatible with cell survival and proliferation. In order to investigate the contribution of other genetic alterations to PADPRP regulation in ES cells, we analysed the expression levels of PADPRP and of other genes, such as oncogenes and tumor suppressor genes, which may enhance the proliferative potential of ES cells. We have detected a positive correlation between the expression levels of the DNA repair enzyme poly(ADP-ribose) polymerase and the dbl proto-oncogene in Ewing's sarcoma cells. The co-regulated expression of these genes has been established in NIH3T3 cells transformed by the human dbl oncogene or by overexpression of the dbl proto-oncogene. In both instances, the increase in dbl expression resulted in elevated levels of PADPRP mRNA and polymerase activity. The dbl oncogene was more efficient than the proto-oncogene in upregulating PADPRP expression. The inability of other oncogenes to upregulate PADPRP upon transformation of NIH3T3 cells demonstrated the specificity of the dbl in the process. Transfection of dbl transformed NIH3T3 cells with retroviral PADPRP vectors resulted in the establishment of clones with PADPRP levels higher than those detectable in untransformed NIH3T3 cells transfected with the same retroviral constructs. These results suggest that dbl plays a role in the mechanism by which mammalian cells autoregulate their endogenous levels of PADPRP. Post-translational modification of the dbl or proto-dbl proteins by cytoplasmic PADPRP does not participate in the mechanism(s) underlying the observed PADPRP/dbl co-regulation. PMID- 7784073 TI - The 8 kD product of the putative oncogene MTCP-1 is a mitochondrial protein. AB - An unusually small (8 kD) protein (p8MTCP-1) is coded by the putative oncogene MTCP-1 (also called c6.1B), involved in the translocation t(X;14)(q28;q11) associated with some mature T-cell proliferations. Here, we show by subcellular fractionation and by confocal microscopy that this protein is located in the mitochondria. This localization orientates toward a role of p8MTCP-1 in the mitochondrial metabolism which may be relevant for the oncogenic process. PMID- 7784074 TI - p53 involvement in control of G2 exit of the cell cycle: role in DNA damage induced apoptosis. AB - DNA damage in proliferating mammalian cells induces a complex cellular response comprising perturbation of the cell cycle and programmed cell death. The relationship between p53-dependent and p53-independent apoptotic cell death, as well as the cell cycle checkpoints induced by DNA damaging agents were explored in hematopoietic cells, using M1 myeloblastic leukemia cells, which are null for p53 expression, genetically engineered M1 variants, expressing p53ts and bcl-2 transgenes, as well as myeloblast enriched bone-marrow cells obtained from wild type p53 (wt p53) and p53-deficient mice. It is shown that gamma-irradiation of M1p53ts cells activated a function of the temperature sensitive mutant transgene p53 (p53ts), promoting increased apoptosis relative to parental, null p53 M1 cells. It is also shown that the kinetics of apoptotic cell death induced by gamma-irradiation correlated with the rapidity of exit from gamma-ray-induced G2 arrest for all the different hematopoietic cell types indicated above. Finally, data has been obtained to demonstrate that, in addition to a role in apoptosis and G1 arrest, wild-type p53 positively modulated the exit from the gamma-ray induced G2 checkpoint. Taken together, these findings indicate that this new function for p53 is a component of the physiological pathway by which p53 exerts its role in apoptosis. PMID- 7784075 TI - p53-mediated transcriptional activity increases in differentiating epidermal keratinocytes in association with decreased p53 protein. AB - The regulation of p53 protein synthesis and p53-mediated gene transactivation were evaluated in cultured mouse keratinocytes maintained as basal cells or induced to differentiate by Ca2+ > 0.1 mM. p53 protein half-life, p53 protein synthesis and the level of p53 mRNA decreased during terminal differentiation, as detected by immunoprecipitation with a panel of p53-specific antibodies and Northern blotting. Thus differentiating keratinocytes have lower levels of p53 protein. This decline is not observed following growth arrest alone, or in papilloma cell lines which do not terminally differentiate in response to Ca2+. In contrast, the ability of endogenous p53 to transactivate transcription from the PG13 CAT plasmid increased during differentiation in vitro. This change in activity cannot be explained by changes in p53 conformation or nuclear localization. Consistent with these findings, mRNA for the p53-mediated genes WAF1 and mdm-2 increased with Ca(2+)-induced differentiation in a time dependent manner, suggesting activation of p53 contributes to the differentiated phenotype. However, p53-null mice exhibit histologically normal skin and epidermal keratinocytes from these mice express the appropriate markers of differentiation and suppression of DNA synthesis in vitro when the [Ca2+] is > 0.1 mM. The observation that proliferating cells have higher levels of p53 protein which is less active for its function than differentiated cell types could have a consequence for the selection of p53 gene mutations during carcinogenesis, depending upon the stage of differentiation of the tumor cell type. PMID- 7784076 TI - Identification of binding domains on the p21Cip1 cyclin-dependent kinase inhibitor. AB - Members of the recently discovered family of cyclin-dependent kinases inhibitors (CKIs) appear to play an essential regulatory role in the control of cell proliferation. To investigate the molecular basis of the interaction between these proteins and the cyclin-dependent kinases (CDKs), we performed a systematic mutagenesis of the CKI family member p21Cip1 using the alanine-scanning strategy. We have examined the interaction between in vitro translated human cdk2, cyclins A and D1, purified proliferating cell nuclear antigen (PCNA) and a set of human p21Cip1 mutants fused to glutathione S-transferase. Independent domains that are required for the interaction with cdk2 and with PCNA have been identified. The cdk2 binding domain is located in the N-terminal part of the protein, between residues 45 and 60, a region that is fully conserved in the p27Kip1 inhibitor. A PCNA binding region was localised to the C-terminus of the protein, between residues 142 and 163. These findings define protein motifs that are highly conserved between members of the CKI family and that are likely to play an essential function in the regulation of the G1/S transition. PMID- 7784077 TI - Critical role of Rho in cell transformation by oncogenic Ras. AB - We demonstrate that Rho, a regulator of cytoskeletal actin, is necessary for Ras transformation. A dominant inhibitory Rho gene (RhoBN19) specifically suppressed Rat1 cell focus formation induced by oncogenic Ras but not by Raf. An activated Rho gene (RhoBV14) lacked focus formation activity but augmented the focus formation activity of both oncogenes. NIH3T3 cell lines expressing RhoBV14 grew to higher saturation density and displayed reduced serum and anchorage requirements for growth. We concluded that Rho played a role in cell growth regulation and was required for transformation by oncogenic Ras but not Raf. A model for Ras signal transduction proposing separate Rho-dependent and Raf dependent pathways is discussed. PMID- 7784079 TI - Ligand-independent activation of tyrosine kinase in fibroblast growth factor receptor 1 by fusion with beta-galactosidase. AB - To examine the biological role of fibroblast growth factor receptor 1 (FGFR1) oligomerization for its signal transduction, we construct an expression vector encoding a FGFR1-beta-galactosidase fusion protein. This vector is designed to fuse the 3'-portion of FGFR1 to beta-galactosidase. Transfection of this vector into FGFR-negative rat L6 myoblast cells results in ligand-independent inhibition of differentiation into myocytes, suggesting that FGFR1 within this fusion protein is constitutively activated. This can be confirmed by demonstrating that this fusion protein exhibits the tyrosine kinase activity and phospholipase C gamma 1 is tyrosine-phosphorylated even in the absence of ligand stimuli. Since the transfected cells also exhibit the enzyme activity of beta-galactosidase which is known to be active only in a tetramer form, this constitutive activation can be elicited by tetramerization of FGFR1. Furthermore, deletion of a region corresponding to C terminal 10 amino acids important for tetramerization of beta galactosidase from this expression vector abolishes the constitutively active nature of FGFR1 with simultaneous loss of beta-galactosidase activity. Transfection of non-deleted expression vector into NIH3T3 cells results in acquisition of focus-forming activity while a deleted form of expression vector fails to show this activity even in the presence of basic FGF. These results would suggest that tetramerization of FGFR1 can produce a constitutively active form responsible for transformation of NIH3T3 cells. PMID- 7784078 TI - Growth suppression of acute promyelocytic leukemia cells having increased expression of the non-rearranged alleles: RAR alpha or PML. AB - The balanced t(15;17) rearrangement found in acute promyelocytic leukemia (APL) cells fuses PML on chromosome 15 to the retinoic acid receptor alpha (RAR alpha) on chromosome 17. PML/RAR alpha is expressed in APL cells with the non-rearranged alleles, PML and RAR alpha. Clinical remissions induced by all-trans-retinoic acid (RA) treatment of APL patients are linked to expression of PML/RAR apha, a transcription factor with reported dominant negative functions. The roles of PML and RAR alpha in the RA response of APL have not yet been fully explored. This study examines these roles by individually transfecting RAR alpha and PML into NB4 APL cells. NB4 is the sole APL cell line containing the t(15;17). RA treatment represses NB4 cell growth and induces a myeloid phentoype. Full length cDNAs for RAR alpha and PML were individually cloned into a CMV-driven expression vector containing the neomycin resistance gene. Surprisingly, none of the obtained stable transfectants expressed exogenous RAR alpha or PML mRNAs even when reverse transcription polymerase chain reaction (RT-PCR) detection assays were used. All clones expressed the neomycin resistance gene and were similar to parental NB4 cells in their growth and differentiation properties. An explanation explored for this lack of gene expression was that increased levels of RAR alpha or PML might suppress APL cell growth. To examine this possibility, transfection experiments were repeated using an episomal vector-based expression system containing an SV40 driven RAR alpha or PML cDNA and the hygromycin B resistance gene. A new selection strategy augmented expression of the desired cDNAs. A control episomal vector lacked a cDNA insert. Following electroporation and selection, exogenous RAR alpha expression was obtained. Compared to controls, the growth of these transfectants was markedly inhibited before and after RA treatment and these cells more prominently induced myeloid maturation markers. In contrast, exogenous PML expression was transient since these transfectants did not appear to propagate in culture. These findings indicate: (1) a growth disadvantage for NB4 cells having increased expression of RAR alpha or PML and (2) increased RAR alpha expression augmented RA-mediated maturation of NB4 cells. This implicates a role for RAR alpha or PML in regulating the growth or differentiation of APL cells. It is hypothesized this occurs through antagonism of PML/RAR alpha actions in these leukemic cells. PMID- 7784080 TI - Expression of beta-galactosidase under the control of the human c-myc promoter in transgenic mice is inhibited by mithramycin. AB - In order to assess the functional contribution of the human c-myc promoter region in the expression of the c-myc gene, transgenic mouse lines containing a bacterial lac Z gene encoding beta-galactosidase under the control of the human c myc protooncogene promoter were generated. Transgenic mouse embryos heterozygous for the human c-myc Z transgene demonstrate high amounts of beta-galactosidase activity as early as day 11 of embryogenesis by histochemical staining of whole embryos using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) as substrate, localizing specifically to early spinal cord tissue. beta galactosidase activity can be demonstrated by histochemical staining in brain tissue of day 14 embryos, localizing mainly to the prefrontal cortex region, while relative amounts of beta-galactosidase in spinal cord tissue are reduced. Determination of specific activity of beta-galactosidase using resorufin-beta galactopyranoside as substrate in homogenates of whole embryos heterozygous for the human c-myc/lac Z transgene demonstrates significantly elevated beta galactosidase activity over control embryos in day 11 and day 14 embryos. Surprisingly, cell homogenates of brain tissue from adult G1 generation mice heterozygous for the human c-myc/lac Z transgene demonstrate greater than 10-fold higher specific activity of beta-galactosidase over normal control brain tissue. Specific inhibition of the c-myc/lac Z transgene was also demonstrated in developing embryos using mithramycin given at a dose of 150 micrograms kg-1 d-1 intraperitoneal to pregnant females on days 7-13 of gestation. Both histochemical staining of beta-galactosidase and specific activity assays of day 14 embryos demonstrated significantly lower levels of beta-galactosidase than untreated controls. These results are unique since we are able to detect expression of beta galactosidase in developing embryonic central nervous system tissue along with adult brain tissue of animals carrying the human c-myc Z transgene and we are able to specifically inhibit expression of the transgene using mithramycin administered in utero. PMID- 7784081 TI - The proto-oncogene FGF-3 is constitutively expressed in tumorigenic, but not in non-tumorigenic, clones of a human colon carcinoma cell line. AB - The human colon carcinoma cell line, SW613-S, is composed of cells with a high level amplification of the MYC proto-oncogene that are tumorigenic in nude mice and of cells with a low-level amplification of MYC that are not tumorigenic. Transcripts from FGF-3, a member of the fibroblast growth factor gene family, accumulate in cells from tumorigenic clones, but are undetectable in those from non-tumorigenic clones. Nuclear run-on analyses indicate that this differential FGF-3 expression is regulated at the level of transcription initiation. Determination of the structure of the FGF-3 transcripts indicates that they are generated by splicing of the three exons and termination at the single polyadenylation site predicted from the genomic sequence. Their size heterogeneity is due to multiple initiation sites spanning a 700 base-pair long promoter region. FGF-3 is activated in tumors induced in nude mice by MYC transfected cells from non-tumorigenic clones. However, in most of the cell lines established from these tumors, FGF-3 expression tends to be lost upon in vitro propagation. Thus, in these transfectant cell lines, the presence of exogenous MYC gene copies is not sufficient to activate FGF-3 expression and in vivo growth is also required. PMID- 7784082 TI - PuF/NM23-H2/NDPK-B transactivates a human c-myc promoter-CAT gene via a functional nuclease hypersensitive element. AB - We have isolated the transacting factor PuF that, through its interaction with a nuclease hypersensitive element (NHE) located upstream of the c-myc gene, transactivates the human c-myc gene in vitro (Postel et al., 1989). PuF was recently identified as being encoded by the nonmetastatic 23-H2 (nm23 H2)/nucleoside diphosphate kinase-B (NDPK-B) gene (Postel et al., 1993). In addition to its ability to transactivate the c-myc gene in vitro, PuF/NDPK-B catalyzes the shuttling of gamma-phosphates between nucleoside triphosphates and diphosphates (Gilles et al., 1991; Postel and Ferrone, 1994) and has been postulated to suppress tumor metastasis (Stahl et al., 1991). Here we have extended our studies of PuF and c-myc transcription by testing whether PuF affects c-myc transcription using a transient transfection assay. A plasmid containing the human c-myc promoter-NHE region was cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene. When cotransfected with a PuF expression vector, CAT activity was elevated 3-4 fold relative to transfections containing the myc-CAT plasmid. In contrast, a myc-CAT reporter plasmid in which the NHE element was deleted showed no increase in CAT activity when cotransfected with the PuF expression vector. From these results we conclude that PuF transactivates the c-myc gene via the nuclease hypersensitive element. PMID- 7784083 TI - Cloning and developmental expression analysis of the murine c-mer tyrosine kinase. AB - We have cloned the putative mouse homologue of the human c-mer receptor tyrosine kinase proto-oncogene. Comparison of the mouse and human c-mer amino acid sequences reveals an overall identity of 88%. Similar to the human, the extracellular region of the murine c-mer protein possesses two amino terminal immunoglobulin-like domains and two membrane proximal fibronectin type III domains, which places it in the Axl family of tyrosine kinases. Our analysis of the Axl family identifies eight different regions of amino acid consensus that have residues characteristic of this and no other tyrosine kinase family; six of the eight are within tyrosine kinase subdomains. The homology within the Axl family is highest between c-mer and c-eyk, the chicken proto-oncogene of the tumor virus gene product v-eyk. Northern analysis of adult tissues suggests that the mouse c-mer, although expressed in many tissues, has an expression pattern unique among Axl family members. In normal adult hematopoietic cells c-mer seems to be expressed predominantly if not exclusively in the monocytic lineage. Mouse c-mer is expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages. This early and consistent expression of c-mer was confirmed during in vitro differentiation of embryonic stem cells. The embryonic expression profile of c-mer suggests that this tyrosine kinase may play an important function in the developing mouse. PMID- 7784084 TI - Identification of p53 target genes through immune selection of genomic DNA: the cyclin G gene contains two distinct p53 binding sites. AB - An immune-selection procedure was employed in order to isolate p53-binding sites from rat genomic DNA. One such site was found to reside within the first intron of the cyclin G gene. Cyclin G mRNA levels are strongly elevated upon induction of wild type p53 activity in cells carrying a temperature sensitive p53 mutant. The cyclin G gene also carries a second p53-binding motif upstream to its transcriptional start site. The presence of two high affinity p53-binding sites may confer upon the cyclin G gene the potential to be activated very efficiently by p53. These data raise the possibility that cyclin G may be a downstream mediator of at least some of the biological effects of p53. PMID- 7784085 TI - Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. AB - We have cloned a new gene, cbl-b, with homology to the c-cbl proto-oncogene. A large protein is predicted (approx. MW 108,000) that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a putative leucine zipper. There is striking nucleotide and amino acid homology to the c-cbl proto-oncogene most notably in the structural motifs described above. Cbl-b is expressed in normal and malignant mammary epithelial cells, in a variety of normal tissues, and in hematopoietic tissue and cell lines. Cbl-b expressions is up-regulated with macrophage/monocyte differentiation of the HL60 and U937 cell lines. There is direct association of the cbl-b protein with the Src Homology 3 domains of several proteins including signaling, cytoskeletal and adaptor proteins. Our data suggest that cbl-b encodes a protein which can interact with signal transduction proteins to regulate their function or to be regulated by them. Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction. PMID- 7784086 TI - Role of the autophosphorylation site on the biological function of pp56lck. AB - Src-family tyrosine kinases act as signaling molecules in a wide array of cellular activation processes. The existence of the various src-family members reflects the requirement for different cell-surface receptors to transmit cell type specific intracellular signals. The structural basis for the functional specificity of src-kinases is being actively investigated. In the present report we have analysed the contribution of the area surrounding the autophosphorylation site (located at subdomain VII of the catalytic domain) in determining src kinases activity and functional specificity. To this end we analysed the kinase activities of the lymphoid src-kinase pp56lck and a mutant of pp56lck in which this region has been exchanged for the corresponding area of the serine/threonine kinase c-Raf. Our studies indicate that the change at subdomain VII affected the ability of pp56lck to phosphorylate physiological substrates. Furthermore, when analysed in T cells, the mutant at subdomain VII failed to induce interleukin-2 production, a specific biological function of pp56lck. Thus, the area surrounding the autophosphorylation site of pp56lck plays a critical role in mediating its specific biological function. PMID- 7784087 TI - Two critical hydrophobic amino acids in the N-terminal domain of the p53 protein are required for the gain of function phenotypes of human p53 mutants. AB - Some mutant forms of the p53 protein have been shown to gain new functions that are not shared by the wild-type p53 protein; (1) mutant p53 proteins can transcriptionally transactivate the multi-drug resistance gene-1 (MDR-1) and (2) when expressed in non-tumorigenic cells with no endogenous p53 protein, mutant p53 proteins can enhance the tumorigenic potential of these cells (Dittmer et al., 1993). It has recently been shown (Lin et al., 1994b) that the transcriptional activator domain of the p53 protein contains two amino acids, leu 22 and trp-23, which are required by the wild-type p53 protein for transcriptional activity. To determine whether these same amino acid residues are utilized by mutant p53 proteins for their gain of function phenotype, the triple mutant p53 protein (at residues 22 and 23 in the transactivation domain and residue 281 in the DNA binding domain--a gain of function mutant) was made. While the p53-281 mutant transcriptionally activates the MDR-1 gene and enhances the tumorigenic potential of cells it is expressed in, the 22, 23, 281 triple mutant failed to carry out either of these functions. PMID- 7784088 TI - Gamma-radiation-induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53. AB - The tumour suppressor gene p53 codes for a transcription factor which is thought to play a critical role in the induction of G1 cell cycle arrest and programmed cell death (apoptosis) following DNA damage by ionizing radiation. The aim of this investigation was to determine whether a p53 independent radiation-induced apoptosis pathway exists in human colon epithelial cell lines. This report describes the induction, by gamma-radiation, of apoptosis in the colorectal adenoma cell line S/RG/C2, and in the colorectal carcinoma cell line PC/JW, both of which lack wild type p53. In addition, flow cytometry revealed that both cell lines failed to arrest in G1 after radiation. Thus, although loss of wild type p53 may abrogate G1 arrest, radiation-induced apoptosis can still occur in human colonic tumour cell lines through a p53 independent mechanism. PMID- 7784090 TI - Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation. AB - In order to examine the role of p53 expression on the sensitivity of cells to radiation-induced reproductive failure, we examined the radiosensitivity of a human diploid fibroblast cell strain (AG1521) before and after transfection with the E6 or E6/E7 genes of human papillomavirus 16 (HPV16)3. HPV E6 binds to p53, promoting its degradation and abrogating wild-type p53 function. AG1521 cells transfected with either E6 or E6/E7 showed no radiation induction of either p53 or WAF1/Cip1. The radioresistance of these cells were significantly increased; the D0 of the survival curves rose from 130 +/- 4 cGy for wild type (neo transfected) cells to 178-192 cGy for three subclones transfected with E6 alone, and 151-218 cGy for eight subclones transfected with E6/E7. The change in radiosensitivity took place before the process of cellular immortalization and transformation produced by transfection with these genes. Thus, the effect on radiosensitivity appears to be an early effect of the loss of p53 function in non transformed cells, perhaps related to the loss of the G1 checkpoint and of the capacity for programmed death amongst radiation damaged cells. PMID- 7784089 TI - Loss of Fas/Apo-1 receptor accelerates lymphomagenesis in E mu L-MYC transgenic mice but not in animals infected with MoMuLV. AB - The Fas/Apo-1 receptor is an integral membrane protein that transduces apoptotic signals upon binding to its natural ligand or to specific antibodies. Loss of Fas/Apo-1 receptor leads in (lpr,lpr) mice to a nonmalignant accumulation of abnormal T-cells very probably due to the lack of induction of apoptosis in peripheral T-cells. It has been reported that soluble forms of Fas/Apo-1 receptor that may interfere with apoptotic signaling occur in patients suffering from various forms of lymphoid neoplasms. Therefore, we wished to investigate whether the loss of proper homeostatic regulation through Fas/Apo-1 receptor mediated apoptosis could influence the process of lymphomagenesis. To this end, we performed two experiments (i) we infected (lpr,lpr) animals with Moloney Murine Leukemia Virus (MoMuLV) that causes T-cell lymphoma in mice and (ii) we crossed (lpr,lpr) animals with E mu L-myc transgenic mice that are prone to develop T- and B-cell lymphoma due to deregulated expression of the L-myc transgene by the immunoglobulin enhancer E mu. We find that infection with MoMuLV did not accelerate the formation of lymphoid neoplasms in (lpr,lpr) mice when compared to infected normal animals. However, E mu L-myc/(lpr,lpr) animals that constitutively express the L-myc transgene in the lymphoid lineage clearly show accelerated formation of T- and B-cell lymphoma when compared to normal E mu L myc transgenics. These data demonstrate that in cooperation with particular oncogenes impairment of Fas/Apo-1 receptor function can indeed affect and modulate the process of tumor formation. PMID- 7784092 TI - RET mutations in exons 13 and 14 of FMTC patients. AB - RET is a receptor tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as for Hirschsprung disease (HSCR), a congenital disorder affecting the intestinal motility. Germ-line mutations in the RET exons 10 and 11 were demonstrated in the majority of the MEN 2A and FMTC patients. On the other hand, one codon of RET exon 16 is preferentially changed in MEN 2B patients. Recently, a germ-line mutation in the exon 13 was described in one FMTC family as well as in four sporadic MTCs. In the present study, we observed the same exon 13 mutation in two FMTC families. In addition, we identified a previously unreported substitution of RET exon 14 in two unrelated FMTC families. Both mutations segregate with the disease in these four FMTC families and involve the tyrosine kinase domain of RET. Haplotype analysis using polymorphic markers tightly linked to the RET gene indicates that in each pedigree the mutation arose as an independent event. PMID- 7784091 TI - Tyrosine phosphorylation of Shc proteins and formation of Shc/Grb2 complex correlate to the transformation of NIH3T3 cells mediated by the point-mutation activated neu. AB - PLC-gamma, ras-GAP and Shc have been proposed to be in vivo substrates for the neu-encoded p185neu receptor tyrosine kinases. We compared the tyrosine phosphorylation levels of PLC-gamma, ras-GAP and Shc in two NIH3T3 derived cell lines, transformed B104-1-1 and non-transformed DHFR/G8 cells in which point mutation activated and normal rat neu genes were transfected and expressed, respectively. We found that tyrosine phosphorylation of Shc and formation of Shc/Grb2 complex were more significant in B104-1-1 cells than in DHFR/G8 cells, while no obvious difference could be detected for the tyrosine phosphorylation levels of ras-GAP and PLC-gamma between these two cell lines. Furthermore, we observed that association with Shc was severely impaired by deletion of most of the major autophosphorylation sites of the point-mutated neu. The truncated neu product, however, fully retained its ability to transform NIH3T3 cells, induce Shc tyrosine phosphorylation and Shc/Grb2 complex formation. Our results suggest that tyrosine phosphorylation of Shc which allows formation of Shc/Grb2 complex may play an important role for cell transformation induced by the point mutation activated neu, and that stable binding to mutant p185neu may not be necessary for Shc to mediate this signaling pathway. PMID- 7784093 TI - The role of p53 in coordinated regulation of cyclin D1 and p21 gene expression by the adenovirus E1A and E1B oncogenes. AB - Expression of the cyclin D1 gene is induced when quiescent fibroblasts are stimulated to reenter the cell cycle by addition of growth factors. Moderate ectopic expression of cyclin D1 in early G1 facilitates progression through G1. When transiently overexpressed at the G1/S boundary, cyclin D1 prevents S phase entry, suggesting a dual role for this protein in cellular growth control. It was shown that the retinoblastoma protein (pRB) can activate cyclin D1 gene expression; furthermore, there is evidence that expression of the cyclin D1 gene is down-regulated by the SV40 large T and adenovirus E1A genes, both of which were shown to target pRB. We now report that in diploid human fibroblasts functional inactivation of pRB by adenovirus E1A is not sufficient for efficient repression of cyclin D1 gene expression, since the E1B gene product, in addition to E1A, is required for repression of the cyclin D1 gene. Since E1B was shown to target p53, we investigated the role of p53 for expression of the cyclin D1 gene. In a cell line with temperature-sensitive p53, cyclin D1 is moderately expressed at the restrictive temperature. Induction of p53 function by temperature shift leads to an increase of cyclin D1 mRNA and protein, parallel to the activation of p21WAF-1/CIP1 gene expression in this system. When the capability of adenovirus gene products to affect expression of either gene was analysed, we found that infection of Ad5 drastically reduced cyclin D1 and p21WAF-1/CIP1 gene expression in cells where p53 function is limiting. Under these conditions E1A and E1B cooperate to reduce the cyclin D1 level, while p21WAF-1/CIP1 expression was found insensitive to E1A expression. In cells containing elevated p53 function, modulation of gene expression by E1B was severely compromised; under these conditions, expression of E1A reduced expression of cyclin D1 without affecting p21WAF-1/CIP1. The data suggest that E1A and E1B cooperate to inhibit expression of cyclin D1 and identify the cyclin D1 gene as a new downstream target for p53. PMID- 7784094 TI - Characterisation of the interaction between PCNA and Gadd45. AB - We have examined the interaction between the DNA replication and repair protein PCNA, and the growth arrest and DNA damage induced protein Gadd45. An anti-Gadd45 polyclonal antibody co-immunoprecipitates PCNA but in reciprocal experiments, an anti-C terminal anti-PCNA antibody failed to co-immunoprecipitate Gadd45. We used a yeast two hybrid assay to demonstrate that human Gadd45 interacts with both human and S. pombe PCNA. We have determined that the N-terminal 94 amino acids of Gadd45 bind to PCNA, and using a series of N-terminal and C-terminal deletions of human PCNA we have mapped two potential Gadd45 binding sites. Deletion of the last 6 amino acids of PCNA ablated interaction, suggesting a role in Gadd45 binding. This explains the inability of an anti-C terminal PCNA antibody to co immunoprecipitate Gadd45. Using a peptide ELISA approach, we showed that Gadd45 protein binds strongly to three regions of PCNA (residues 1-20, 61-80, and 196 215) and weakly to residues 121-170. The crystal structure of PCNA provides insight into our genetic and immunochemical data. Our results confirm an interaction between PCNA and Gadd45, define regions of both molecules involved in this interaction, and are consistent with a potential stoichiometry of 2 Gadd45 molecules to each PCNA monomer. These data provide support for the notion that PCNA-Gadd45 interactions co-ordinate cell cycle and DNA repair. PMID- 7784096 TI - Genomic stability and wild-type p53 function of lymphoblastoid cells with germ line p53 mutation. AB - Increased cancer risk associated with germ-line p53 mutation was linked to a deficit in the ability to maintain genomic stability. Accordingly, normal fibroblasts from cancer-prone individuals accumulate genomic aberrations with concomitant loss of wild-type p53 allele during in vitro culture. We tested whether such changes also occur in EBV-immortalized lymphoblastoid cells. Both normal and p53 germ-line mutant lymphoblastoid cells maintained functional p53 and genomic stability during long term in vitro culture. These unexpected differences between fibroblastic and lymphoblastic cells suggest that phenotypic expression of p53 deficiency is cell type specific. This could contribute to selective tissular localization of tumours observed in patients with Li-Fraumeni syndrome despite the presence of a mutant p53 allele in all cells. PMID- 7784095 TI - HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone independent growth in human breast cancer cells. AB - Growth of human breast cells is closely regulated by steroid hormone as well as peptide hormone receptors. Members of both receptor classes are important prognostic factors in human breast cancer. Clinical data indicate that overexpression of the HER-2 gene is associated with an estrogen receptor-negative phenotype. In this study, we demonstrate that introduction of a HER-2 cDNA, converting non-overexpressing breast cancer cells to those which overexpress this receptor, results in development of estrogen-independent growth which is insensitive to both estrogen and the antiestrogen, tamoxifen. Moreover, activation of the HER-2 receptor in breast cancer cells by the peptide growth factor, heregulin, leads to direct and rapid phosphorylation of ER on tyrosine residues. This is followed by interaction between ER and the estrogen-response elements in the nucleus and production of an estrogen-induced protein, progesterone receptor. In addition, overexpression of HER-2 receptor in estrogen dependent tumor cells promotes ligand-independent down-regulation of ER and a delayed autoregulatory suppression of ER transcripts. These data demonstrate a direct link between these two receptor pathways and suggest one mechanism for development of endocrine resistance in human breast cancers. PMID- 7784097 TI - One or two genetic loci mediate high opiate analgesia in selectively bred mice. AB - The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U 50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques. PMID- 7784099 TI - Effects of inflammatory irritant application to the rat temporomandibular joint on jaw and neck muscle activity. AB - An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the activity of jaw and neck muscles could be influenced by injection of the small-fibre excitant and inflammatory irritant mustard oil into the region of the temporomandibular joint (TMJ). Injection of a vehicle (mineral oil, 20 microliters) did not produce any significant change in EMG activity. In contrast, injection of mustard oil (20 microliters, 20%) evoked increases in EMG activity in the jaw muscles but not in the neck muscles. The increased EMG activity evoked by mustard oil was reflected in 1 or 2 phases of increased activity. The early EMG increase occurred soon after the mustard oil injection (mean latency +/- SD: 3.5 +/- 2.3 sec), peaked within 1 min, and then subsided (mean duration: 7.5 +/- 5.2 min). The later EMG increase occurred at 14.6 +/- 10.0 min after the mustard oil injection and lasted 14.3 +/- 12.3 min. These excitatory effects of mustard oil on the EMG activity of jaw muscles appear to have a reflex basis since they could be abolished by pre-administration of local anaesthetic into the TMJ region. These results document that TMJ injection of mustard oil results in a sustained and reversible activation of jaw muscles that may be related to the reported clinical occurrence of increased muscle activity associated with trauma to the TMJ. PMID- 7784098 TI - The consumption of fentanyl is increased in rats with nociceptive but not with neuropathic pain. AB - The question whether opioids relieve neuropathic pain remains a controversial issue. Experimental as well as clinical studies report contradictory results. This study investigated the consumption of fentanyl, a short-acting opioid, in rats with neuropathic pain, induced by partial sciatic nerve injury. The experiment consisted of a drug choice procedure in which the animals could choose between a solution containing 0.008 mg/ml of fentanyl and a highly palatable sweet solution. It was reasoned that if opioids have an analgesic effect in neuropathic pain, this will reinforce the intake of fentanyl more so in rats with neuropathic pain than in pain-free controls. This protocol was previously already used by Colpaert et al. (1982) in a rat model of chronic pain of nociceptive origin, namely polyarthritis. No significant differences were found in the relative oral intake of the fentanyl solution in mononeuropathic and pain-free control rats. In contrast, rats with nociceptive pain, adjuvant monoarthritis, drank significantly more of the fentanyl solution than did control rats. These data give experimental support for the clinical findings that opioids have a poor analgesic effect in neuropathic pain. PMID- 7784100 TI - Effects of an acute muscle nerve section on the excitability of dorsal horn neurones in the rat. AB - A previous study of this laboratory showed that an acute myositis (which is associated with increased activity in slowly conducting muscle afferent fibres) is followed by marked excitability changes in the dorsal horn within a few hours. The present work addresses the question as to how the responsiveness of dorsal horn neurones changes when the same muscle nerve is transected. In anaesthetized rats, an axotomy of the gastrocnemius-soleus (GS) muscle nerves was performed and the electrical and mechanical excitability of single dorsal horn neurones in the lumbar spinal cord determined 2-8 h after the lesion. Axotomy led to a decrease in the proportion of neurones responding to A-fibre input from the cut nerve and to an increase in the efficacy of sural and peroneal nerve stimulation. The change in GS input became significant only 5-8 h after the lesion and could reflect the beginning of neuroplastic changes. The change in sural and peroneal input was most marked 2-5 h after axotomy and is probably due to fast neuronal processes. The efficacy of C-fibre input from the sural and peroneal nerves increased significantly in the lateral dorsal horn only. In comparison with the effects of an acute myositis, the axotomy had opposite effects with regard to the GS input, but similar effects with regard to the C-fibre drive from the other nerves. It is concluded that transection of a muscle nerve is similarly effective in inducing acute changes in dorsal horn excitability as is an increase in muscle nerve activity. PMID- 7784101 TI - The effect of abdominal surgery on thresholds to thermal and mechanical stimulation in sheep. AB - Thresholds to noxious mechanical and thermal stimulation were measured in 6 groups of sheep prior to induction of anaesthesia and subsequently for a period of 2 h in the post-anaesthetic period. Groups 1-4 were anaesthetised using thiopentone and underwent ventral midline laparotomy. Four animals (group 5) underwent anaesthesia but not surgery, and a further 6 sheep (group 6) undergoing surgery were anaesthetised using ketamine. Groups 1-3 were intravenously administered the following drugs intra-operatively: flunixin meglumine, carprofen and buprenorphine, respectively. Groups 4-6 received no additional treatment. Thresholds to the mechanical test were not changed in the post-anaesthetic period for any group. There was a significant reduction in the responses to thermal stimulation after surgery for sheep in group 4 (45 and 60 min), while sheep in group 2 had thresholds to thermal stimulation greater than those recorded in the remaining groups at all time points post-operatively. Responses to thermal stimulation in sheep undergoing anaesthesia but not surgery (group 5) were unaltered during the 2 h recording period after anaesthesia ended. These data indicate that abdominal surgery induces thermal but not mechanical hyperalgesia in sheep, which appears to be centrally mediated. Moreover, the absence of mechanical hyperalgesia raises the possibility that central changes in noxious information processing may not be detected using mechanical stimuli in the same time course as thermal stimuli. PMID- 7784102 TI - Subanesthetic concentrations of lidocaine selectively inhibit a nociceptive response in the isolated rat spinal cord. AB - Systemically administered local anesthetics are known to provide analgesia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In the present study, the effects of low (subblocking for nerve conduction) concentrations of lidocaine on a spinal cord nociceptive potential were studied. Spinal cords were removed from neonatal rats and maintained in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Following a stabilization period (60-120 min) with control measurements, each preparation was exposed to a single concentration of lidocaine (30-60 min) then returned to control perfusate for recovery (60-120 min). Data were digitized and integrals computed for both monosynaptic and slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow-VRP. At lidocaine concentrations of 1-10 micrograms/ml (3.6-36 microM), the slow-VRP was reduced from 79% to 36% of control. Recovery to pre exposure control levels was slow and sometimes not complete after 60-120 min in drug-free perfusate. The monosynaptic component of the VRP was unaffected by lidocaine at any concentration, suggesting that the depression of the slow-VRP cannot be attributed to simple conduction block. The addition of naloxone 0.1 microM to the perfusate had minimal effect on lidocaine-induced depression. Although resembling the selective effects of morphine, the antinociceptive effects of lidocaine do not appear to be primarily mediated through opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784103 TI - Prostanoid synthesis in the spinal cord enhances excitability of dorsal horn convergent neurones during reperfusion of ischaemic receptive fields on the rat's tail. AB - In 40 rats anaesthetized with enflurane, we identified convergent dorsal horn neurones responding to both noxious (pinch) and innocuous (brush) mechanical stimulation of their receptive fields on the tail. We recorded extracellular activity before and during ischaemia of the receptive fields, as well as during subsequent reperfusion. Two NSAIDs, indomethacin and diclofenac sodium, or saline were applied locally to the spinal cord before the induction of ischaemia. During ischaemia, spontaneous activity of the neurones increased significantly, and the responses to both pinch and brush were reduced significantly; indomethacin and diclofenac sodium had no effect on either spontaneous activity or sensitivity to mechanical stimuli. The neurones became hypersensitive to both pinch and brush during reperfusion of their receptive field, and receptive field size increased. Application of indomethacin and diclofenac sodium to the spinal cord abolished both the hypersensitivity and the increase in receptive field size. Our results indicate that spinal cord prostanoid synthesis facilitates the enhanced excitability of dorsal horn convergent neurones to both noxious and innocuous mechanical stimuli during reperfusion of their receptive fields, but does not affect the neurones' responses to receptive field ischaemia, nor their responses to mechanical stimuli in the absence of a conditioning stimulus. PMID- 7784104 TI - The effect of past-injury on pain threshold and tolerance. AB - Forty male veterans who had been injured during their military service in the Israeli Defense Forces were assessed for pain threshold and tolerance in a thermal pain procedure. Based on their medical records, subjects were classified by three independent judges as having been either severely or lightly injured. Veterans who had been severely injured had much higher threshold and tolerance for thermal pain as compared to lightly injured veterans. These results are interpreted as supporting adaptation-level theory, which implies that painful experiences can change the internal anchor points for the subjective evaluation of pain. PMID- 7784105 TI - Confirmatory factor analysis of a 4-factor model of chronic pain evaluation. AB - Extending the earlier work of Mikail et al. (1993), a confirmatory factor analysis (CFA; LISREL VII) of a 4-factor model of pain assessment was tested. This model, comprised of the Beck Depression Inventory (BDI) and 13 subscales of the McGill Pain Questionnaire (MPQ) and the West Haven-Yale Multidimensional Pain Inventory (WHYMPI), adequately accounted for the pain experience with minimal overlap. Subjects were 306 outpatient chronic pain patients seen at a multidisciplinary chronic pain clinic. Subscale scores were subjected to CFA procedures that yielded a well-fitting final model that explained 91% of the covariance in the observed data. This final model was derived through an exploratory post-hoc procedure that allowed for correlated errors among subscales of the same instrument. The 4 factors were identified as Affective Distress, Support, Pain Description, and Functional Capacity. Results supported the hypothesis that the MPQ, WHYMPI and BDI are representative of the multidimensionality of the pain experience with minimal overlap among measures. Theoretical and clinical implications of reducing the overlap among existing measures in the assessment of pain patients are discussed. PMID- 7784106 TI - The Chronic Pain Coping Inventory: development and preliminary validation. AB - This paper describes the development and validation of a measure of strategies used by patients to cope with chronic pain, the Chronic Pain Coping Inventory (CPCI). A 104-item measure of pain coping responses and 3 measures of functioning were completed by 176 chronic pain patients. Two-week retest data were provided by 111 of these patients. Item and scale analyses resulted in a 65-item measure that assessed 11 pain coping dimensions. This inventory was then cross-validated in a second sample of chronic pain patients (n = 78), who also completed a measure of pain-related distress. The significant others (typically, spouses) of patients in the second sample rated patients on a significant-other version of the CPCI and on other measures of patient functioning. The results support the reliability of the CPCI scales. Four scales (Guarding, Resting, Asking for Assistance, and Task Persistence) predicted patient- and significant other reported patient adjustment. Eight scales (Guarding, Opioid Medication Use, NSAID Use, Sedative-Hypnotic Medication Use, Resting, Asking for Assistance, and Exercise/Stretch) demonstrated moderate-to-strong relationships between patient and significant-other versions, further supporting their validity. PMID- 7784107 TI - Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to central sensitization. AB - Allodynia is a well-known component of neuropathic pain resulting from injury to the nervous system. Clinical pain states with allodynia in connection with longstanding superficial wounds have, however, not been reported in the literature. In this case a chronic pain state developed in a previously healthy 17-year-old girl in and around a persistently suppurating appendectomy wound. There was no spontaneous pain but pronounced allodynia in the wound and in the surrounding skin. Quantitative thermal tests showed abnormal thresholds for several sensory modalities confirming abnormal processing of sensory input from the involved area. The pattern of sensory abnormalities evaluated with thermal testing changed transiently and the allodynia diminished during a phentolamine block. Since the pain responded poorly to opioids and ketamine has been reported to reduce allodynia, it was administered in a sub-dissociative bolus dose during wound dressing. The wound was essentially unchanged after treatment for 3 months but the allodynia and sensory aberrations had decreased significantly. We interpret these results as a de-sensitizing effect in the long term of repeated NMDA-receptor blockade by ketamine in a chronic pain state, with indications of central sensitization, partially maintained by sympathetic activity. PMID- 7784108 TI - Phantom limb pain: are cutaneous nociceptors and spinothalamic neurons involved in the signaling and maintenance of spontaneous and touch-evoked pain? A case report. AB - A patient suffered multiple fractures of the right leg and a left brain-stem infarction involving the anterolateral fasciculus of the central nociceptive system following multiple trauma. Later, the right leg was amputated, resulting in spontaneous and touch-evoked phantom pain and mechanical stump allodynia. However, quantitative sensory testing revealed considerable impairment of sensations normally mediated by cutaneous nociceptors and central spinothalamic systems on the right body side, including the stump but nearly intact touch and vibration senses. Quantitative assessment of peripheral nociceptive C-fiber function (axon reflex vasodilatation and flare) showed no abnormalities on both sides. Sympathetic blocks did not change spontaneous and evoked pain. Epidural and spinal anesthesia abolished evoked pain but had no effect on spontaneous phantom pain. Extirpation of a neuroma of the sciatic nerve did not alter spontaneous and evoked pain. TENS resulted in an increase in pain. We concluded the following. (i) Painful somatosensory memories that are responsible for phantom limb pain are located in the brain, most probably in the thalamus or cortex. (ii) Touch-evoked phantom pain and stump allodynia are not mediated by cutaneous nociceptive C and A delta fibers and spinal nociceptive pathways (spinothalamic tract). Activity in the lemniscal system (low-threshold mechanoreceptive A beta afferents, dorsal columns and medial lemnicus system) may be transferred to central pain signaling neurons in the thalamus or cortex resulting in touch-evoked pain sensations. (iii) Ongoing activity in cutaneous nociceptive C fibers and spinal nociceptive systems is not necessary to maintain central processes that account for spontaneous and touch-evoked pain sensations. Activity in nociceptors of deep somatic tissues might be more important. PMID- 7784109 TI - The riddle of trigeminal neuralgia. PMID- 7784110 TI - Anti-inflammatory efficacy of treatments with aspirin and acetaminophen. PMID- 7784111 TI - Comments on DeConno (Pain, 55 (1993) 383-385) and Brown (Pain, 56 (1994) 139-143) PMID- 7784112 TI - A comparison of the chest radiograph and computerised tomography in assessing lung changes in acute spinal injuries--an assessment of their prevalence and the accuracy of the chest X-ray compared with CT in their assessment. AB - Lung function in patients following an acute spinal injury is frequently much more compromised than may be expected from the level of injury and the chest radiograph appearance. Experimental evidence in anaesthetised patients and subsequently our own experience with patients with acute spinal injuries suggested that in paralysed patients lung changes were frequent and that in many spinal patients large pleural effusions and lung consolidation could be present without the usual associated chest radiograph changes being recognised. This study was performed to assess the prevalence of chest pathology and the sensitivity of the chest radiograph in portraying it. Sixty patients (50 males, 10 females, 31 cervical, 29 thoracic or thoracolumbar; 15 incomplete, 45 complete; ages 17-66, mode 22 years) with spinal injuries from a variety of causes were assessed with a supine chest radiograph and three computerised tomography axial cuts at standardised locations through the thorax. The chest radiograph agreed with the computerised tomography in only 12 patients (six normal, six abnormal). The chest radiograph suggested that there were 19 normals but computerised tomography only showed 12. In a total of 35 patients, the chest radiograph significantly underestimated the degree of change and in 13 the chest radiograph suggested greater pathology than was shown on computerised tomography. Thirteen of the 20 patients with cervical lesions but no chest trauma had lung changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784113 TI - Restoration of gait by functional electrical stimulation in paraplegic patients: a modified programme of treatment. AB - Restoration of standing and of gait by functional electrical stimulation in clinically complete paraplegic patients was modified in the course of treatment and in the stimulation parameters. By substituting an initial cyclic muscle strengthening with an active stimulated standing, four patients with T3-11 lesions started walking with electrical stimulation in 10-17 days. They walked without ankle-foot orthoses. With a satisfactory stride length of 0.75-0.97 m, their gait velocity ranged from very slow to that of a leisurely healthy gait. Already established stimulation of the quadriceps muscles for standing and of the peroneal nerves for lower limb flexion during the swing phase of gait was applied. Diminished limb flexion after several weeks was restored by an increase of the stimulation frequency of the peroneal nerve from 20 to 60 Hz. EMG and kinesiological measurements displayed an improved direct response of the ankle as well as of the reflex mediated hip, knee and ankle flexion response. At the same time stimulation frequency was reduced to 16 Hz for the quadriceps muscles in order to reduce fatigue. PMID- 7784114 TI - The management of upper urinary tract calculi by piezoelectric extracorporeal shock wave lithotripsy in spinal cord injury patients. AB - From May 1988 to September 1994, 15 spinal cord injury patients were treated by piezoelectric extracorporeal shock wave lithotripsy. Aged from 23 to 71 years (mean = 39), they presented with a total of 23 stones, of which 18 were located in the calyces, three in the renal pelvis and two in the proximal ureter. The maximum dimensions of calculi varied from 5 to 35 mm (mean = 11). Patients were placed in a dorsal decubitus position during the sessions, three being sedated with diazepam, while the other 12 remained unsedated. All were treated routinely with systemic antibiotics. Auxiliary procedures consisted of two pyelocalyceal flushings, three double J ureteral stenting and three ureteroscopies with fragment removal with a Dormia basket. No episode of autonomic dysreflexia was observed. Short term side effects were limited to a few cases of gross haematuria which regressed spontaneously. Overall, eight successes (53%), and seven failures (47%), were registered. Of the failures, one was the result of a partial fragmentation, while six were related to intrarenal retention of residual fragments resulting in four cases in rapid recurrences. Extracorporeal shock wave lithotripsy can be easily applied to spinal cord injury patients. Its usefulness and limitations need to be well understood and a global consideration must be applied to the prevention and early detection of the upper urinary calculi in this exposed population of patients. PMID- 7784116 TI - Early progressive changes in tissue viability in the seated spinal cord injured subject. AB - The patient with spinal cord injury is at high risk of tissue breakdown at all times due to a number of adverse factors, such as reduced mobility and anaesthesia. It is therefore essential that each patient is prescribed appropriate support media during initial rehabilitation. In this study, the effectiveness of prescribed wheelchair cushions has been assessed in terms of tissue response at the ischial tuberosities. A total of 42 subjects who had sustained traumatic spinal cord injury within 1 year were monitored on at least two occasions during initial rehabilitation. Changes in transcutaneous gas response (TcPO2 and TcPCO2) were monitored concurrently with regional interface pressures. A series of six transcutaneous gas variables were established, as markers of tissue viability. Non-parametric statistical analyses revealed some significant correlations between these variables. The results of this study also indicate that (1) spinal cord injury subjects with lesions below T6 show a progressive decrease in ability to maintain blood flow in sitting on prescribed support cushions and (2) SCI subjects with lesions above T6 show a progressive improvement in tissue viability status at the seating support interface. Therefore results imply that paraplegics are at a potentially higher risk of tissue breakdown than tetraplegics and thus require effective support cushions with strict adherence to a pressure relief regime. PMID- 7784117 TI - Efficacy of rowing, backward wheeling and isolated scapular retractor exercise as remedial strength activities for wheelchair users: application of electromyography. AB - Shoulder dysfunction due to regular wheelchair use is a common problem among people with spinal cord injuries. As a remedial measure, strengthening of the scapular retractor muscles has been suggested. Electromyographical analysis was utilized to examine scapular retraction muscle use during rowing, backward wheeling and a standardized scapular retraction exercise in seven people with spinal cord injuries and seven able bodied subjects. In addition, a pilot study using indwelling electrodes was completed to validate the use and placement of surface electrodes. Both rowing and the standardized scapular retraction exercise recruited higher levels of retractor involvement than backward wheeling. We suggest that rowing, because of its value as a cardiovascular exercise and high level of retractor recruitment, is an appropriate and effective means of remediating scapular retractor weakness. PMID- 7784118 TI - Radiological percutaneous gastrostomy placement for enteral feeding. AB - Many patients who are unable to swallow have normal intestinal absorption and therefore do not need expensive and potentially problematic parenteral nutrition. Long term nasogastric tubes are unpleasant and interfere with communications, thus a gastrostomy is often felt to be appropriate. Traditionally this has been inserted at laparotomy but recently, other less invasive techniques of insertion such as endoscopy have been used for placement. We describe three patients where a percutaneous gastrostomy was placed by a radiological technique that we feel deserves wider recognition. It is quicker, cheaper and more versatile than the endoscopic method and avoids the unpleasant necessity for intubation by other than a fine-bore nasogastric tube. PMID- 7784115 TI - Degeneration of axons in the corticospinal tract secondary to spinal cord ischemia in rats. AB - Occlusion of the thoracic aorta and both subclavian arteries (XC) in the rat model produces spastic paraplegia. In order to characterize the lesion of white matter, 14 male Sprague-Dawley rats underwent XC for 10.5 to 12 min, were observed for 32 days and assessed with a lesion score. A sham group of eight underwent surgical manipulations without XC. The spinal cords were studied by optical microscopy and electron microscopy. An additional group of normal animals (n = 8) underwent spinal cord blood flow measurement with the autoradiographic technique. Optical microscopy showed normal histology in sham operated rats and rats with aortic cross-clamp and lesion score = 2-4 (n = 5), rare changes in the white matter of rats with lesion score = 8 (n = 2), and demyelination of the anterior and lateral tracts of the white matter and motor neuron loss in the gray matter of rats with lesion score = 13-15 (n = 7) and spastic paraplegia. In this last group, electron microscopy disclosed severe axonal degeneration of corticospinal tracts. In the same region spinal cord blood flow was higher than the remaining white matter. This study confirms that spastic paraplegia observed in the rat model after XC is due to degeneration of the pyramidal tracts, perhaps more susceptible to injury due to the high spinal cord blood flow. PMID- 7784119 TI - Trimethoprim-sulfamethoxazole prophylaxis against urinary tract infection in the chronic spinal cord injury patient. AB - Suppressive therapy with antibiotics has long been thought to decrease the number of complications from the neuropathic bladder in spinal cord injury patients, but it may also induce resistance to antibiotics which subsequently causes difficulties in treating symptomatic urinary tract infections. Forty-three chronic spinal cord injury patients were randomized to continue to receive daily trimethoprim-sulfamethoxazole (TMP-SMX) urinary tract prophylaxis versus discontinuing antibiotic prophylaxis. Patients were all at least 6 months after spinal cord injury. Patients were followed for a minimum of 3 months, with weekly catheter urine cultures. The difference in the colonization rate at onset and after 3 months (percent of cultures with asymptomatic bacteriuria) between the control and prophylaxis group was not statistically significant (P > 0.1). There was a significant decrease in the percentage of TMP-SMX resistant asymptomatic bacteriuria in the control group, 78.8%, compared to 94.1% in the suppressive group (P < 0.05). There was no significant difference in the number of symptomatic urinary tract infections following the withdrawal of suppressive therapy between the control group, 0.035/week, and the prophylaxis group, 0.043/week (P > 0.5). There was a larger percentage of TMP-SMX resistant symptomatic urinary tract infections in the treated group, 42.5% versus 37.5% in the control group, but the difference was not significant (P > 0.5). Irrespective of the method of bladder management, suppressive therapy with TMP-SMX did not reduce the incidence of symptomatic bacteriuria and did increase the percentage of cultures resistant to TMP-SMX in asymptomatic patients. PMID- 7784120 TI - Compliance and complications of clean intermittent catheterization in the spinal cord injured patient. AB - The optimal management of the neuropathic bladder secondary to spinal cord injury remains unsettled. Some have advocated the use of chronic indwelling catheters in tetraplegic patients supposedly due to comparable complication rates with non indwelling catheter management. We assessed the urological complication and compliance rates in a group of spinal cord injured patients followed over a mean of 5.9 years. Complication rates from clean intermittent catheterization were comparable if not better than the rates previously reported for clean intermittent catheterization and significantly better than chronically catheterized patients. The compliance rate in our series was 71% as determined by the number of patients remaining on clean intermittent catheterization at their last urological follow-up. We conclude that the use of clean intermittent catheterization can provide optimal management of the lower urinary tract in spinal cord injured patients. PMID- 7784121 TI - Heterotopic ossification and rhabdomyolysis. AB - Heterotopic ossification and rhabdomyolysis are well described entities but, as far as we know, their association has never been described in the literature. We recently treated a patient who presented with this association. After a suicide attempt, this patient developed rhabdomyolysis of the left upper and lower limbs with peripheral neurological impairment. Two months later radiographs showed ectopic ossification around the left hip. Rhabdomyolysis is underdiagnosed, and is due to local disturbance of the calcium-phosphorus metabolism resulting in soft tissue calcifications. Underlying rhabdomyolysis may be a possible aetiology of heterotopic ossification. Recognition of this may help us to understand the pathophysiology and to improve the management of heterotopic ossification. PMID- 7784122 TI - Brucellar spondylitis mimicking lumbar disc herniation. Case report. AB - In this paper, a patient with brucellar spondylitis who was initially diagnosed as having a lumbar disc herniation is presented. As the disc tissue enlarges in the early stages of discitis because of the inflammatory reaction, it may compress the related root(s) mimicking a disc herniation. For this reason infectious discitis, as in our case, should be kept in mind in the differential diagnosis of the radicular symptoms caused by a disc herniation. The crucial role of magnetic resonance imaging in making the differential diagnosis of the case is especially emphasized. PMID- 7784123 TI - Prolonged fever and heterotopic ossification in a C4 tetraplegic patient. Case report. AB - Prolonged fever is an uncommon diagnostic problem in a spinal cord injury patient. The underlying causes include recurrent infections, thromboembolic phenomena and central fever. We report a case of heterotopic ossification in a traumatic C4 tetraplegic patient presenting as prolonged fever of 3 months' duration. Treatment with oral indomethacin led to prompt resolution of the fever and acute manifestations of heterotopic ossification. The efficacy of indomethacin in the treatment of heterotopic ossification in spinal cord injury needs to be further confirmed in larger studies. PMID- 7784124 TI - A commercial vaccine for ovine toxoplasmosis. AB - This paper describes the development of the first commercial vaccine for toxoplasmosis. The vaccine comprises live tachyzoites of the S48 'incomplete' strain of Toxoplasma gondii and is deployed to control toxoplasma abortion in sheep. A discussion of protective immune mechanisms and recent studies on host responses to the vaccine is also included. PMID- 7784126 TI - Field trials of an asexual blood stage malaria vaccine: studies of the synthetic peptide polymer SPf66 in Thailand and the analytic plan for a phase IIb efficacy study. AB - Several years ago the Walter Reed Army Institute of Research (WRAIR) initiated an independent analysis of the candidate malaria blood stage vaccine SPf66. WRAIR contracted for the synthesis and formulation of SPf66 in United States Food and Drug Administration (FDA) inspected laboratories within the U.S., and in 1992, filed an Investigational New Drug (IND) application with the FDA. Preclinical studies indicated that the vaccine could be synthesized to meet its release specifications, and when adjuvanted with alum, was essentially equivalent to Colombian produced SPf66 in regards to immunogenicity in preclinical studies of rodents and primates, and in human volunteers in Phase I studies. The goal of these efforts was ultimately to conduct a Phase IIb field trial to determine the safety and efficacy of SPf66 produced under current Good Manufacturing Practices (cGMP). Such a trial is currently underway in a malaria endemic refugee camp along the Thai-Burmese border. Here we briefly describe the study and present the formal analytic plan that was submitted to regulatory authorities in the United States for analysis of the study results. We believe such independent confirmatory studies are an essential part of the vaccine development process and are required to provide important data regarding the safety and efficacy of candidate vaccines in diverse geographical regions, and as a means to assess their role in the context of broader malaria control programmes. PMID- 7784125 TI - The development of oral vaccines against parasitic diseases utilizing live attenuated Salmonella. AB - Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area. PMID- 7784127 TI - Field trials of a recombinant rabies vaccine. AB - To improve both safety and stability of the vaccines used in the field to vaccinate foxes against rabies by the oral route, a recombinant vaccinia virus, expressing the glycoprotein of rabies virus (VVTGgRAB) has been developed. VVTGgRAB innocuity was verified in target species and in domestic animals as well as in numerous wild animal species that could compete with the red fox in consuming vaccine baits in Europe. Oral immunization of foxes, by distributing VVTGgRAB vaccine-baits, was undertaken for the whole infected area in Belgium (10,000 km2). Five campaigns of fox vaccination, were carried out from autumn 1989 until 1991. Each time, 150,000 vaccine-baits were dropped by air at a mean density of 15 per km2. These campaigns induced a drastic decrease in the incidence of rabies and the elimination of the disease from 80% of the initially infected area. Regarding the geographical evolution of rabies in Belgium and in adjacent regions in neighbouring countries, new spatial strategies for bait dispersal were planned for 1992, 1993 and 1994: successive confined campaigns were carried out along political borders only. These campaigns induced a new decrease of incidence; no rabid fox could be detected in 1993 in spite of an improved epidemiological surveillance. In 1994, rabies was again confirmed in 13 foxes collected in an area close to the French border. These cases demonstrated the persistence of a border rabies focus and justify further restricted vaccination campaigns. PMID- 7784128 TI - Commercialisation of a recombinant vaccine against Boophilus microplus. AB - Increasingly, there is need for methods to control cattle tick (Boophilus microplus) infestations by the use of non-chemical technology. This need is brought about by a mixture of market forces and the failure or inadequacy of existing technology. A recombinant vaccine has now been developed against the tick. This vaccine relies on the uptake with the blood meal of antibody directed against a critical protein in the tick gut. The isolation of the vaccine antigen, Bm86, and its production as a recombinant protein is briefly described. The vaccine has been tested in the field, has been taken through the full registration process and is now in commercial use in Australia. A related development has occurred in Cuba. The potential for improvement of the current vaccine and for the development of similar vaccines against other haematophagous parasites is discussed. PMID- 7784129 TI - Taenia ovis recombinant vaccine--'quo vadit'. AB - Several years have elapsed since the publication by Johnson et al. (1989) of the cloning of a recombinant antigen from the cestode parasite Taenia ovis which stimulated high levels of protective immunity in sheep. A great deal of subsequent research and development was necessary to bring the fledgling vaccine to the point of being a registered commercial product. The results of these subsequent studies are dealt with briefly in this paper, including the results of field trials. The T. ovis vaccine was registered by the New Zealand Animal Remedies Board in February 1994. Where then is the commercial product? This paper gives a background to market problems which have emerged through the politics (and realities) of the NZ T. ovis control campaign. It serves as notice that the best science dedicated to producing vaccines or products for parasitic, or other, diseases often faces significant hurdles in the real world of commerce and politics. PMID- 7784130 TI - The practicality and sustainability of vaccination as an approach to parasite control. AB - The development of a successful vaccine depends not only on the production of the vaccine itself, but also on the design pf the vaccination programme. This involves a better understanding of the epidemiology of the disease to be controlled, the delivery system to be used and the costs involved. This review focuses on current understanding of parasite population dynamics and epidemiology, and on the logistic experience gained from immunization programmes using existing viral and bacterial vaccines. The feasibility and sustainability of any new vaccine would greatly benefit from research into epidemiology and health systems which are conducted in parallel, rather than sequential to, vaccine development. PMID- 7784131 TI - Reduction of cytochrome aa3 measured by near-infrared spectroscopy predicts cerebral energy loss in hypoxic piglets. AB - Near-infrared spectroscopy is a noninvasive monitoring technique that allows quantitative measurement of changes in cerebral oxygenated Hb (HbO2), deoxygenated Hb (Hb), total Hb, and oxidized cytochrome aa3 (CytO2). Changes in cerebral Hb oxygenation and CytO2 have been measured in human neonates and infants under a variety of conditions. However, the association of these measurements with cerebral high-energy phosphate loss is not known. We studied simultaneous changes in cerebral HbO2, Hb, total Hb, and CytO2 by near-infrared spectroscopy and changes in nucleoside triphosphate (NTP, mostly ATP) and phosphocreatine (PC) concentrations and intracellular pH by in vivo 31P-labeled magnetic resonance spectroscopy. Four-wk-old piglets (n = 8) underwent sequential hypoxic episodes of increasing severity (inspired O2 concentration, 12, 8, 6, 4, and 0%). Animals were anesthetized and mechanically ventilated. At all levels of hypoxia, cerebral HbO2 decreased, and Hb increased. Loss of PC or NTP was not observed until inspired O2 concentration was decreased to less than 12%. With such severe hypoxia, hypotension, intracellular acidosis, and increasingly severe PC and NTP depletions occurred. Decreases in PC and NTP correlated closely with decreased CytO2 and arterial blood pressure (p < 0.0001) but not with changes in HbO2 and Hb. In conclusion, cerebral hypoxemia is readily detected by near infrared spectroscopy as a decrease in HbO2 and an increase in Hb. However, relative changes in cerebral HbO2 and Hb have low predictive value for cerebral energy failure. Reduction of CytO2 is highly correlated with decreased brain energy state and may indicate impending cellular injury. PMID- 7784132 TI - Glial fibrillary acidic protein in the cerebrospinal fluid: a possible indicator of prognosis in full-term asphyxiated newborn infants? AB - Glial fibrillary acidic protein (GFAP) is the structural protein of intermediate filaments in astroglia. GFAP has extensively been used as a marker of gliosis in neuropathology. It also appears in excessive amounts in the cerebrospinal fluid in various acute brain disorders. Hypoxic-ischemic encephalopathy after perinatal asphyxia is a condition in which levels of GFAP could be expected to be elevated if brain cell damage occurs. We examined levels of GFAP by a sensitive ELISA in the cerebrospinal fluid of full-term infants between 12 and 48 h after birth. Cerebrospinal fluid-GFAP increased 5-fold in infants after perinatal asphyxia compared with a reference group (675 versus 137 ng/L, p < 0.001). The levels of GFAP also increased gradually in accordance with the severity of the neurologic symptoms ranked as degree of hypoxic-ischemic encephalopathy. We conclude that the cerebrospinal fluid levels of GFAP might be an important adjunct in the neonatal assessment of infants subject to perinatal asphyxia, and together with other neuronal or glial proteins, it might also help in defining temporal relationships in asphyxia. PMID- 7784133 TI - Surfactant treatment at birth reduces lung vascular injury and edema in preterm lambs. AB - To study the effect of surfactant administration on fluid balance in the premature lung, we measured pulmonary vascular pressures, lung lymph and pleural liquid flow, and concentrations of protein in lymph, pleural liquid, and plasma before and after birth in 12 chronically catheterized preterm lambs (127-128 d gestation) treated with either placebo or surfactant just before surgical delivery. Eight lambs received intrapulmonary saline (placebo), and four lambs received surfactant; all lambs were mechanically ventilated with O2 for 8 h after birth. In control lambs, lung lymph and pleural liquid flow increased from 2.7 +/ 0.4 mL/h during the 2-4 h before birth to 9.2 +/- 2.1 mL/h by 6-8 h after birth; lymph and pleural space protein drainage increased from 58 +/- 7 mg/h during the 2-4 h before birth to 134 +/- 25 mg/h by 6-8 h after birth. In lambs treated with surfactant, there was no significant increase in lymph and pleural liquid flow after birth (before birth, 2.3 +/- 0.3 mL/h; 6-8 h after birth, 3.4 +/- 0.9 mL/h); likewise, lymph and pleural space protein drainage did not change after birth (before birth, 54 +/- 6 mg/h; 6-8 h after birth, 50 +/- 8 mg/h). Postmortem extravascular lung water was significantly less in lambs treated with surfactant compared with control lambs (control, 6.5 +/- 0.3 g/g dry lung; surfactant treated, 5.0 +/- 0.2 g/g dry lung).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784134 TI - Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant. AB - The effect of the addition of surfactant protein (SP)-B or SP-B plus SP-C (SP-BC) to a surfactant made from bovine lung (Survanta) was evaluated in 27-d-gestation preterm rabbits. The animals were treated with Survanta, Survanta + 2% SP-B, Survanta + 3% SP-BC, or sheep surfactant. They were then ventilated with 3 cm H2O positive end-expiratory pressure and tidal volumes of 8 mL/kg. Survanta + 2% SP-B was prepared by adding SP-B in water to Survanta or by adding SP-B in chloroform [SP-B(Chl)] to lipid-extracted Survanta. Dynamic compliances of the Survanta + 2% SP-B(Chl)- and Survanta + 3% SP-BC-treated rabbits were greater (p < 0.05) than those treated with Survanta or Survanta + 2% SP-B in water and were comparable to sheep surfactant. Postventilation pressure-volume curves for the groups treated with Survanta supplemented with SP-B had significantly larger retained volumes on deflation compared with those treated only with Survanta (p < 0.01). The effects of ventilation style on the responses were assessed by ventilating other groups of rabbits treated with Survanta, Survanta + 0.5% SP-B(Chl), Survanta + 2% SP B(Chl), or sheep surfactant with tidal volumes of 10 mL/kg and 0 cm H2O positive end-expiratory pressure. SP-B (2%) augmented the in vivo function of Survanta without positive end-expiratory pressure, and 0.5% SP-B had no effect. Infasurf, a surfactant with more SP-B, was more effective than Survanta when tested in the preterm rabbits. SP-B is a critical factor for optimum immediate surfactant function. PMID- 7784135 TI - Effects of triiodothyronine on retention of beta-adrenergic responsiveness of voltage-gated transmembrane calcium current during culture of ventricular myocytes from neonatal rabbits. AB - To study the effects of triiodothyronine (T3) on responsiveness of L-type calcium currents to beta-adrenergic stimulation in neonatal hearts, ventricular myocytes were isolated from neonatal rabbits and cultured in medium containing 10% fetal bovine serum to which T3 had been added to achieve either hypothyroid, euthyroid, or hyperthyroid conditions, as assessed by measurement of free T3 concentrations. During a 24-h culture period, the striated rod-shaped myocardial cells progressively assumed a stellate shape with reduced surface area; however, the rate constants for diffusion of Na+ from a microelectrode pipette into the cells remained unchanged. Voltage-dependent characteristics of L-type calcium currents as assessed by whole-cell voltage clamp studies were also unchanged after culture with various concentrations of free T3. By contrast, the stimulation of voltage gated transmembrane calcium current from baseline by isoproterenol was reduced (p < 0.05) in hypothyroid cells (15 +/- 8%; n = 14) compared with either euthyroid (86 +/- 15%; n = 18), hyperthyroid (54 +/- 16%; n = 12) or freshly isolated (50 +/- 12%; n = 10) myocytes. The differences in beta-adrenergic responsiveness of voltage-gated transmembrane calcium current to isoproterenol between euthyroid, hyperthyroid, and freshly isolated cells were not significant (p > 0.05). These results indicate that retention of beta-adrenergic responsiveness of voltage gated transmembrane calcium current in neonatal cardiac myocytes depends on physiologic amounts of active thyroid hormone. Our culture method for neonatal cardiac myocytes will be useful for studying physiologic modulation of beta adrenergic responsiveness. PMID- 7784136 TI - Organization and fine structure of a pacemaker derived from fetal rat myocardium. AB - At an unknown point in mammalian development, cardiac precursor cells become committed to the cardiocyte phenotype. Certain of these are believed to specialize further into pacemaker cardiocytes. By culturing explanted embryonic ventricles into in vivo organ culture (Tucker DC, Snider C, Woods WT Jr: Pediatr Res 23:637-642, 1988), we observed pacemaker cells arising apparently from cardiocytes. We hypothesized that this event can be triggered by intercellular attachments, innervation, vascularization, or other factors. The present study was designed to test the hypothesis that primitive ventricular cells in the tubular heart can organize into an anatomically and electrophysiologically distinct pacemaker structure in the absence of innervation or vascularization from extrinsic sources. Developing ventricles of tubular hearts from 10-d-old rat embryos (n = 22) were excised and incubated in culture dishes. Within each explant, a group of cells organized into a uniform cluster (diameter, 150 +/- 50 microns) after 8 +/- 2 d in culture. These cells resembled immature conduction system cells and had electrophysiologic features similar to those of mature pacemaker cells. Single-cell action potentials and impulse conduction patterns proved that the pacemaker cluster was the dominant pacemaker for the entire explant. These results confirm that, in the absence of extrinsic nerves and blood vessels, culture of the tubular ventricle elicits formation of an organized pacemaker, resembling the mature cardiac pacemaker and suggesting that contact with the culture dish surface or some other factor triggers conversion of cardiocytes to the pacemaker phenotype. PMID- 7784138 TI - Development and maturation of the autonomic nervous system in premature and full term infants using spectral analysis of heart rate fluctuations. AB - The changes in the power spectra of heart rate (HR) fluctuations, in particular the total power (within 0.02-2.0 Hz) and the power in the low- (0.02-0.2 Hz) and high- (0.2-2.0 Hz) frequency ranges, were computed from the ECG and respiratory signals of 59 premature and full-term infants. The objective of the study was to investigate the development and maturation of the autonomic nervous system from the first day of extrauterine life to several weeks of postnatal age. The study population was divided into four age groups. Group A: seven 1-d-old premature infants with gestational age of 34-35 wk. Group B: 28 premature infants 7-49 d old with a conceptional age of 34-35 wk. Group C: seven 1-d-old full-term infants of 39-41 wk gestation. Group D: six premature infants 35-97 d old with a conceptional age of 39-40 wk. Mean HR (+/- SEM) of groups C and D combined, i.e. 135 +/- 2 bpm, was significantly lower compared with groups A and B, i.e. 152 +/- 2 (p < 0.01). The mean (+/- SEM) of the low- to high-frequency power ratio obtained from the HR power spectrum decreased progressively from 71 +/- 31 in group A to 34 +/- 8 in group B, 16 +/- 3 in group C, and 17 +/- 2 in group D. The mean low to high ratio for the combined groups C and D, 17 +/- 1, was significantly lower compared with the combined group A and B, i.e. 44 +/- 9 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784137 TI - Heart rate-dependent characteristics of diastolic ventricular filling in the developing chick embryo. AB - The contributions of the early (passive) and late (active) components of ventricular filling have been reported to decrease and increase, respectively, during chick embryo cardiac development. We hypothesized that the observed changes in ventricular filling during early cardiac development results from a decrease in cycle length. We studied the effect of development and cycle length on atrioventricular inflow in 28 chick embryos, Hamilton-Hamburger stages 17, 24, and 26. Cycle length was perturbed (range 240-1040 ms) in ovo by transiently heating or cooling the sinus venosus. Atrioventricular inflow and dorsal aortic velocities were obtained by 20-MHz pulsed Doppler flow-meter and digitally recorded at 500 samples per second. Stroke volume was calculated from dorsal aortic velocity and cross-sectional area. The atrioventricular inflow wave form was integrated and partitioned by area and percentage of total into early (passive) and late (active) components using three methods. Regardless of method, the proportion of filling volume due to the early and late components was cycle length and stage dependent (p < 0.05). The early and late filling volumes were large in the older embryos, and during cycle length decrease (heart rate increase) the early filling volume decrease was greater than the late filling volume decrease. When compared with the percentage of intrinsic heart rate, the percentage of stroke volume due to early filling decreased as heart rate increased and was greater in younger embryos at all heart rates. That due to late filling increased as the percentage of intrinsic heart rate increased. Ventricular filling characteristics are both developmentally determined and cycle length dependent. PMID- 7784139 TI - A potential role for adenosine in the inhibition of nonshivering thermogenesis in the fetal sheep. AB - Adenosine is released by the placenta into the fetal circulation and has potent antilipolytic properties in vitro. Nonshivering thermogenesis cannot be demonstrated by cooling fetal sheep in utero but can be induced by supplemental oxygenation and umbilical cord occlusion; this suggests the presence of inhibitor(s) of placental origin. To test whether circulating adenosine could be such an inhibitor, a series of experiments was carried out in nine fetal sheep at 136-145 d gestation. Birth was simulated in utero by sequentially cooling the fetus 2.49 +/- 0.23 degrees C with no change in the low levels of plasma FFA or glycerol; ventilating with O2 via an exteriorized tracheostomy tube and umbilical cord occlusion. Thermogenic indices rose markedly, and plasma FFA and glycerol concentrations peaked at 725 +/- 88 microEq/L (p < 0.01) and 771 +/- 154 mumol/L, (p < 0.001), respectively, O2 consumption rose to 20 +/- 2 mL/min/kg, and temperature increased 1.99 +/- 0.35 degrees C. The long-acting adenosine analog N6-(L-2-phenylisopropyl)-adenosine (PIA) was then infused (90 micrograms/kg bolus, then 300 micrograms/kg/h for 30 min); plasma FFA and glycerol decreased to 265 +/- 56 microEq/L (p < 0.003) and 477 +/- 102 mumol/L (p < 0.04), respectively; O2 consumption fell rapidly to 4.5 +/- 0.3 mL/min/kg (p < 0.01); temperature decreased 1.89 +/- 0.39 degrees C (p < 0.001); and fetal arterial BP decreased to 38 +/- 5 mm Hg (p < 0.004) in 30 min. A stepped dose-response study was performed in three fetal sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784140 TI - Dietary sodium modulates neonatal but not adult cardiac atrial natriuretic peptide in rats. AB - After an initial postnatal diuresis, neonates are in positive sodium balance. Because atrial natriuretic peptide (ANP) contributes to sodium homeostasis, this study was designed to evaluate the maturational effects of increased dietary sodium intake on cardiac ANP production. Preweaned Sprague-Dawley rat pups were artificially reared by feeding them either a normal-sodium or high-sodium diet for 7 d and were compared with maternally reared rat pups. Adult rats were divided into three groups: the first group was given ad libitum rat food and 1% sodium chloride to drink, the second group was pair-fed with this group but given tap water to drink, and the third group was fed ad libitum rat food and water for 10 d. Atrial and ventricular pro-ANP and ANP contents and plasma ANP concentrations were measured by RIA. Steady state atrial and ventricular ANP mRNA expression was determined by Northern and dot-blot analysis. There was a 2-fold increase in atrial pro-ANP and ANP content and a 50% decrease in plasma ANP concentration in preweaned rat pups fed a high-salt diet. In contrast, atrial pro ANP and ANP content and plasma ANP concentration were not affected by increased sodium intake in adult rats. Atrial and ventricular ANP mRNA levels and ventricular pro-ANP and ANP contents were not altered by dietary sodium at either age. We conclude that chronic increase in sodium intake in the preweaning period results in increased storage of atrial pro-ANP. The decrease in plasma ANP concentration in these preweaned rats may be due to reduced basal secretion or enhanced degradation of the peptide. PMID- 7784141 TI - Effect of chronic infusion of cortisol on renin gene expression and renin response to hemorrhage in fetal lambs. AB - In the ovine fetus, plasma renin levels increase close to term, and renin responses to various stimuli are enhanced when compared with responses earlier in gestation. These changes are accompanied by increases in renal renin gene expression and renin content, and they occur in conjunction with elevations in fetal plasma cortisol. Thus, the purpose of this study was to test the hypothesis that a chronic, physiologic elevation in fetal plasma cortisol in early gestation would increase activity in the renin-angiotensin system prematurely. We studied fetuses (control, n = 8; cortisol infused, n = 11) at 94 +/- 2 d of gestation. Fetal vessels were catheterized, and cortisol or saline solution was infused for 6 d. At the end of infusion, fetuses were hemorrhaged approximately 30% of estimated blood volume. Blood samples were collected to measure plasma renin concentration. Then the animals were killed, and kidneys were removed to measure renin mRNA and renin content. Plasma cortisol concentrations in the control and cortisol-treated animals were 7.2 +/- 0.8 and 57.7 +/- 8.6 nmol/L (p < 0.01), respectively. Basal plasma renin concentrations were similar in the two groups 3.2 +/- 0.4 versus 4.4 +/- 1.8 ng of angiotensin I/mL/h, and there was a significant increase after hemorrhage in the cortisol-treated group only. Renal renin content and mRNA levels were similar in the two groups. These data indicate that chronic increases in cortisol in fetal lambs at 0.65 gestation significantly enhance the renin response to hemorrhage but do not alter renal renin gene expression. PMID- 7784142 TI - Role of metallothionein and cysteine-rich intestinal protein in the regulation of zinc absorption by diabetic rats. AB - Hyperzincuria and low Zn absorption in diabetic animals and humans have prompted speculation that diabetics are more susceptible to Zn deficiency. There is little information, however, describing the effects of diabetes on the biochemical mechanisms of intestinal Zn transport. We evaluated Zn absorption in streptozotocin-induced diabetic rats based on a model of Zn transport in which cysteine-rich intestinal protein serves as an intracellular carrier that is inhibited by metallothionein (MT). Apparent absorption and retention of Zn and Cu in rats fed a purified diet were measured in a balance study 15-17 d after induction of diabetes. The rate of 65Zn absorption from isolated intestinal segments, molecular distribution of 65Zn in mucosal cytosol, and tissue MT levels were measured on d 20-22. Food consumption, and thus Zn and Cu intake, by diabetic rats was twice that of controls. Although fractional absorption (percent) of Zn and Cu was lower in the diabetic rats, net absorption (micrograms/100 g body weight/d) was higher. The higher net absorption in the diabetic group was offset, however, by higher urinary excretion, so that Zn and Cu retention was similar in both groups of animals. Low fractional absorption is attributable to the down-regulation of intestinal Zn transport, as indicated by the lower rate of 65Zn absorption from isolated intestinal segments in the diabetic rats. Down-regulation of intestinal transport is in turn attributable to higher concentrations of intestinal MT, which resulted in more 65Zn in the mucosal cytosol bound to MT, an inhibitor of Zn transport, and less to cysteine rich intestinal protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784143 TI - Dietary nucleotides enhance plasma lecithin cholesterol acyl transferase activity and apolipoprotein A-IV concentration in preterm newborn infants. AB - The activity of lecithin cholesterol acyl transferase (LCAT), a key enzyme in lipoprotein metabolism, is low in newborn preterm infants. It has been suggested that a normal gastrointestinal function might be necessary to induce a postnatal increase of LCAT activity because apoproteins A-I and A-IV (apoA-I and apoA-IV) synthesized in considerable amounts in the intestine are known activators of LCAT. Dietary nucleotides have been reported to enhance intestinal growth and maturation; therefore, we hypothesized that nucleotide supplementation to formulas for preterm infants may influence LCAT activity. To investigate this hypothesis, two groups of preterm infants were fed either a nucleotide-free formula or a nucleotide-supplemented formula during the first month of life. The plasma LCAT activity, plasma levels of apoA-I and apoA-IV, plasma cholesteryl esters, and plasma fatty acid composition of cholesteryl esters and phospholipids were then determined. Infants receiving nucleotides had higher LCAT activities and apoA-IV levels than those receiving the nucleotide-free formula for a few weeks. The changes in apoA-IV levels were highly correlated with those of the LCAT activities. However, there were no significant correlations between changes in LCAT activity and plasma cholesteryl esters or phospholipids. These findings indicate that nucleotide supplementation to formulas for preterm infants may improve dietary lipid tolerance by enhancing plasma LCAT activity, probably as a result of an increase in apoA-IV plasma concentrations; they also suggest that nucleotides may enhance apoA-IV synthesis in the intestine during the neonatal period. PMID- 7784144 TI - Correlations between maternal metabolism and deranged development in the offspring of normal and diabetic rats. AB - In an attempt to define the pathogenesis of congenital malformations in diabetic pregnancy, a number of serum factors were determined in normal and diabetic pregnant rats and correlated to the outcome of gestation with the aid of multivariate linear regression analysis. The animals were from two different lines of Sprague-Dawley rats with documented differences in rates of fetal dysmorphogenesis in diabetic pregnancy. The diabetic rats increased less in body weight than the normal rats, yet displayed increased liver and kidney weights. The serum concentrations of glucose, beta-hydroxybutyrate, triglycerides, the branched-chain amino acids, and asparagine, proline, alanine, citrulline, tyrosine, and ornithine were increased by diabetes. In contrast, IGF-I, glutamic acid, glutamine, cystine, and lysine were decreased in the serum of the diabetic pregnant rats. The maternal metabolic imbalance exerted profound effects on embryonic development. Thus, the embryos of the diabetic rats were smaller, had fewer somites, and contained less DNA and protein than the control embryos. In addition, the resorption and malformation rates were increased in the embryos of the diabetic rats. The regression analysis of the data revealed significant interrelationships between adverse embryonic outcome (rates of malformations and resorptions) and the maternal serum concentrations of glucose, triglycerides, beta-hydroxybutyrate, branched-chain amino acids, and creatinine. This suggests that the maternal metabolism of the three major classes of nutrients covariates with the embryonic development in diabetic rat pregnancy. The monitoring of only one of these maternal parameters, e.g. the serum glucose concentration, may therefore not adequately predict the developmental status of the offspring. Our results suggest that the pathogenesis of fetal malformations in diabetic pregnancy is multifactorial. Thus, maintaining metabolites from all nutrient classes at a normal level may be important in preventing adverse fetal outcome. PMID- 7784145 TI - Fatty acid oxidation in peripheral blood cells: characterization and use for the diagnosis of defects of fatty acid oxidation. AB - Disorders of mitochondrial fatty acid oxidation are increasingly recognized as an important group of inborn errors of metabolism that are associated with a significant, but easily preventable, morbidity and mortality in children. However, diagnosis is often delayed because there is no easily applied method that detects all defects. Therefore, we have characterized the acylcarnitine intermediates of fatty acid oxidation in peripheral blood cells from healthy control volunteers and patients with four different defects. After selective permeabilization with histone II AS, a novel permeabilizing agent, the cells were incubated with [U-14C]hexadecanoate and beta-oxidation flux and the acylcarnitine esters formed were measured. Blood cells from the control population produced large amounts of 3-hydroxyacylcarnitines and 2-enoylcarnitine esters, in addition to saturated acylcarnitine esters. This result is different from that found in other tissues (fibroblasts and muscle), where only saturated acylcarnitine esters could be detected. In blood cells from patients with defects of enzymes involved in long-chain fatty acid oxidation, flux was significantly reduced at 15 to 20% of control values (7.1 +/- 2.3 nmol C2 units formed per minute per International Unit of citrate synthase activity). There was a characteristic accumulation of acylcarnitines that was pathognomonic for the site of the defect. Thus, analysis of beta-oxidation intermediates from blood cells allows unequivocal identification of the four most common beta-oxidation defects. PMID- 7784147 TI - [Magnetic resonance imaging of sacral insufficiency fractures: characteristic features and differentiation from sacral metastasis]. AB - Seven patients with sacral insufficiency fractures and seven patients with sacral metastasis were studied with MR imaging. The diagnoses were confirmed with other imaging modalities and clinical follow-up. The insufficiency fractures appeared as bands of abnormal signal: low signal intensity on T1-weighted images and slightly low to iso signal intensity on T2-weighted images. The lesions were delineated better on T1-weighted images than on T2-weighted images. The sacral alae were involved in all patients; five patients had bilateral lesions. The lesions that run across the sacral body were seen in three cases. Inclined coronal images were useful in demonstrating the pattern of distribution of the sacral insufficiency fractures. In three patients with follow-up MR studies, the lesions were markedly reduced or disappeared. The sacral metastatic tumors were of low signal in density on T1-weighted images and iso to high signal in density on T2-weighted images. The extent and distribution patterns of the lesions were various. It is possible to differentiate sacral insufficiency fractures from sacral metastases based on their distribution patterns on MRI. However, if the diagnosis is uncertain or if the symptoms persist or become worse, follow-up MR studies may be necessary. PMID- 7784146 TI - Identification of a unique form of protein C in the ovine fetus: developmentally linked transition to the adult form. AB - To investigate fetal development of protein C, a pregnant ovine model was used. Protein C was isolated from ovine plasma, and a polyclonal antibody was raised. Citrated plasma was obtained from undisturbed chronically catheterized fetal lambs. On Western blot, nonreduced adult ovine protein C had a molecular mass of 70 kD. Fetal ovine protein C was determined to have a molecular mass of 4 to 6 kD larger than the adult molecule. Crossed immunoelectrophoresis demonstrated slightly increased anodal migration of the fetal form. Isoelectric focusing demonstrated a decreased pI of the fetal molecule (4.45 versus 4.6). The ovine protein C molecules were deglycosylated with N-glycanase. Deglycosylated fetal protein C migrated more similarly to the adult form, although a portion of the fetal form persisted. These experiments demonstrate the first example of a unique fetal form of a vitamin K-dependent protein and are compatible with increased glycosylation of fetal ovine protein C. It is speculated that altered posttranslational processing may exist as a general process by which certain coagulation proteins are modified during fetal development. mRNA was isolated from maternal and fetal hepatic tissue and analyzed by Northern hybridization. Fetal plasma concentration and hepatic mRNA for protein C were both 40% of normal maternal values from midgestation onward. At term, protein C mRNA increased to adult range (p < 0.025), although plasma protein C concentration decreased slightly (p < 0.001). A transition from fetal to adult protein C form was found beginning 6 d before term birth, with a doubling time of 24 h. These data are compatible with a gestationally determined maturation of ovine protein C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784149 TI - [Detectability of hypervascular small hepatocellular carcinoma by dynamic spiral CT]. AB - Thirty-one cases of small hepatocellular carcinoma (HCC) under 3 cm in diameter underwent Spiral CT with bolus injection of contrast medium (Dynamic Spiral CT). Dynamic Spiral CT was compared with CT after intra-arterial injection of iodized oil (Lipiodol-CT). The detectability of 79 nodules of small HCC on early phase images of Dynamic Spiral CT was 49.4% (32.6% for those under 1 cm in diameter, 58.3% for 1-2 cm, 91.7% for 2-3 cm). The detectability of small HCCs above the hilum of the liver was better than that below the hilum. Five lesions were detected only on delayed CT images, but not on early phase CT images. Dynamic Spiral CT is useful for detecting hypervascular small HCCs, and both early phase and delayed CT images must be obtained. PMID- 7784148 TI - [Evaluation of anastomosis between intrahepatic or extrahepatic vessels by intra arterial digital subtraction angiography using carbon dioxide]. AB - Carbon dioxide (CO2) intraarterial subtraction angiography (IADSA) was performed in 31 patients with various hepatobiliary diseases. The injection sites of CO2 were proper hepatic artery (10/31; group A), segmental hepatic artery (18/31; group B), and peripheral inferior phrenic artery (3/31; group C), respectively. In group A, only the third order branches of the portal venous system were visualized anterogradely in 8 of 10 patients. In group B, the microcatheter was placed coaxially through a 5 French guiding catheter at the main arterial supply of the tumor in 7 patients and at the peripheral segmental branch of the hepatic artery in 11 patients. The portal venous system was visualized retrogradely in all of the patients regardless of the injection site. The injected CO2 may flow back into the portal vein through the anastomosis known as the peribiliary or periportal plexus. In group C, not only the portal vein but also the pulmonary artery or pericardial vein were visualized by this method. CO2-IADSA was useful to image the minute communications between the various vessels, which have been not hitherto visualized by iodinated contrast medium. PMID- 7784150 TI - [Alginate gel beads for chemoembolization: initial report]. AB - Alginate gel beads (AGB) were studied as a new material for chemoembolization therapy. AGB were quickly produced by dripping a sodium alginate solution through a cannula into a calcium chloride solution, with bead size controlled by cannular size. AGB containing adriamycin or contrast medium were produced from the corresponding mixture. Sixty percent of adriamycin was eluted from AGB within one hour and 90% within 24 hours, while 95% of iopamidol was eluted in 30 minutes. AGB released these contents slower than gelatin sponge particles. Four dogs underwent transcatheter hepatic arterial embolization with AGB. Normal daily activity was recorded until sacrifice on the fourteenth day. There was no hepatic infarction in those embolized with AGB of 0.5 to 1.0 mm in diameter. Partial liver infarction was found in one with compelled embolization and in two with fragile beads. These observations suggested that AGB constitute an instantly preparable embolic material with slow-release activity and flexible solidity. PMID- 7784152 TI - [Application of digital tomosynthesis to radiographic diagnosis of the temporal bone: studies on visualization in normal subjects]. AB - To examine the usefulness of digital tomosynthesis for conducting radiographic diagnosis of the temporal bone, visualization of various aural structures such as the semicircular canals, cochlea, vestibular apparatus, ossicles of the ear and facial nerve canal was examined in 18 volunteers. The visualization of temporal bone specimens by digital tomosynthesis and CT images (slice thickness: 1.5 mm) was compared. The results showed that this system (Digital Tomosynthesis) produced clear images of bony labyrinthine structures such as the semicircular canals, cochlea, and vestibular apparatus. Visualization of the ossicles was also clear, and their continuity could be comprehended better than on CT images. This system also provided good visualization of the labyrinthine and tympanic parts of the facial nerve canal, although CT images had greater sharpness. Visualization of the lower half of the mastoid part was poor with this system. PMID- 7784151 TI - [MR imaging of intramuscular hemangiomas]. AB - Magnetic resonance images of eight surgically confirmed intramuscular hemangiomas were correlated with the pathologic findings. T1- and T2-weighted images were obtained in all cases; STIR images were also obtained in six cases, and fat suppressed enhanced images in seven cases. All eight hemangiomas showed markedly high signal intensity on T2-weighted images. Linear and round low-signal intensity components within hemangiomas corresponded to fibrous tissues, high flow vessels and phleboliths. Fat-suppressed enhanced images were superior to images without fat suppression in defining the extent of lesions. STIR images were useful in defining the extent of hemangiomas with infiltration into surrounding tissues. MRI is useful for distinguishing intramuscular hemangiomas from other soft tissue tumors and also supplies valuable information about the extent of the lesions. PMID- 7784153 TI - [Dose-volume histogram analysis of patients with hepatocellular carcinoma regarding changes in liver function after proton therapy]. AB - Seventy-five patients with hepatocellular carcinoma were treated with proton beams from 1983-1993 at the Proton Medical Research Center, University of Tsukuba. For the purpose of confirming the feasibility of proton therapy for hepatocellular carcinoma, we investigated the influence of proton therapy on liver function and also tried to evaluate the possibility of optimization using dose-volume histogram (DVH) analysis. The results indicated that proton therapy did not cause clinically symptomatic damage in liver function and the only notable change after proton therapy was the transient increase of transminase. DVH analysis showed that this transient increase of transaminase was well correlated to the normal tissue complication probability (NTCP). These results indicate that localized high dose radiation using proton beams is feasible for the treatment of liver cancers and optimization of this treatment may be possible using DVH analysis. PMID- 7784155 TI - [Assessment by three-dimensional CT of pleural indentation or invasion by peripheral lung cancer]. AB - We evaluated the effectiveness of three-dimensional (3D) CT for pleural indentation or invasion by peripheral lung cancer adjacent to pleura. Pleural indentation was shown in three of nine cases on conventional CT, and six cases were demonstrated three-dimensionally. 3D-CT was superior to conventional CT in demonstrating pleural indentation. Pleural invasion could not be assessed on 3D CT because the pleura adjacent to the tumor was not visualized. PMID- 7784154 TI - [Trial of a small image network system in a radiology department of an university hospital]. AB - This paper describes the construction of an image network system in Shinshu University Hospital, and some of its current issues and advantages. Our discussion is based on our experience with a PACS system. SAIPACS, which was installed in 1990 for use in clinical conferencing and pre- and post-graduate education, and with a new CT and MRI network, which was subsequently introduced in 1993. The SAIPACS interconnects eight digital imaging modalities, including CT, MRI, XTV-DR (including digital tomosynthesis), FCR, nuclear medicine (RI), DSA, US, and a film digitizer (FD), with a workstation. Transmission time from the magnetic disk of each imaging modality to the SAIPACS image disk is not rapid enough. Therefore, we need to select images for transfer that are pertinent to our specific purpose, to complete image transmission within a practically acceptable period of time. The new CT/MRI network is composed of two CT units, two MRI systems, an image processing unit and a Universal Gateway. It provides faster image transmission than the SAIPACS system, because there is no need to reform image data to send them in a reversible compressed form. A versatile network system connected to the SAIPACS and CT/MRI network enables digital image data to be processed and edited and images to be transferred back to SAIPACS for clinical or educational use. PMID- 7784156 TI - [Evaluation of photon-counting X-ray radiography for the detection of pulmonary nodule: a preliminary report on experimental and clinical studies]. AB - To evaluate the utility of photon counting X-ray radiography (quantum radiography: QR) for the detection of pulmonary nodules, experimental and clinical studies were performed in comparison with conventional X-ray (CXR). In the experimental study, spatial resolution was analyzed by using the micro-chart method. The simulated nodule detection study was performed by using a chest phantom. The results were evaluated by means of ROC analysis. In the clinical study, both images of CXR and QR were evaluated in a case of metastatic lung tumor. In the experimental study, the spatial resolution of QR was 200 microns. QR was superior to CXR in detecting simulated nodules in all areas. In clinical cases, QR was superior to CXR in depicting not only normal structures but also retrocardiac and retrodiaphragmatic pulmonary nodules. PMID- 7784157 TI - [19F-MR imaging of transplanted tumor: perfluorochemicals as a fluorine tumor imaging agent]. AB - PURPOSE: The purpose of our study was to detect tumor selectively using 19F magnetic resonance imaging (MRI) and to assess Fluosol-DA, a perfluorochemical emulsion, as a tumor imaging agent for 19F-MRI. MATERIALS AND METHODS: SCC VII cells were transplanted in the right leg of mice. After 6 days, Fluosol-DA was administrated intravenously (40 ml/kg). 19F-MR imaging was performed on a Bruker CSI Omega 2 at 4.7 Tesla using a homemade volume coil. RESULTS: In vitro, the concentration and 19F signal intensity of FDA showed a very high correlation (r = 0.9997). Detection on MRI was possible at a concentration of 2%. In vivo, images of 19F in SCC VII tumors were achieved in animals 2 days after the administration of FDA. CONCLUSION: Our study confirms the feasibility of 19F-MR in vivo imaging of tumors using the fluorine compound FDA. PMID- 7784158 TI - [3D-MR cholangio-angiography]. AB - This report introduces a new 3D-MR cholangioangiography technique using 3D Fast SE MR cholangiography and 3D phase contrast MR angiography for obstructive jaundice. In all eight cases, dilated biliary tracts as well as portal veins were clearly visualized on the same image. This new technique helped to determine the operability and surgical strategy for cases with obstructive jaundice. It also provided anatomical guidance for surgical procedures. This study suggests that this technique may replace the currently used modalities for obstructive jaundice. PMID- 7784159 TI - [Patient insurance in Scandinavia]. PMID- 7784160 TI - [Positive experiences in Scandinavian patient insurance]. AB - Voluntary insurance for the compensation of patients for damage sustained in health care was introduced in Sweden 20 years ago and similar systems exist in Finland, Denmark and Norway. This type of insurance is, or is in the process of becoming, statutory. The basic principle is that the apportioning of blame to any individual(s) is not a prerequisite for compensation to be paid out for injury sustained by a patient. Owing to hospital proprietors and care givers having taken out patient insurance policies with approved insurance companies, it has been possible for damages to be compensated in accordance with current insurance norms and the frequency of lawsuits arising from injury sustained in health care has been minimised. This type of insurance is universally accepted, and has often enabled unfortunate confrontations between doctors and patients to be avoided. PMID- 7784161 TI - [Patient insurance in preventive activities. Wealth of injury material demonstrates risks of complications]. AB - The patient insurance system in Sweden has manifest advantages where the mapping out of complications to medical treatment is concerned. The insurance data base contains a wealth of information which can be used for preventive purposes--not only overall statistics, but also patients' records and expert opinions in damage cases. During the 20 years since patient insurance was introduced, cases of special fundamental interest have been published, injury statistics have reported to clinics and departments, and certain issues have undergone special scrutiny- e.g. neural damage during surgery, infections arising from cataract surgery, bile duct injuries, injuries at delivery and damage resulting from physiotherapy. PMID- 7784162 TI - [Multiple sclerosis--the great imitator!]. AB - Multiple sclerosis (MS) is traditionally a clinical diagnosis based on relapsing and remitting multifocal CNS symptoms. In recent years new diagnostic tools such as cerebrospinal fluid analysis, magnetic resonance imaging and evoked potential testing have been developed. This article reviews diagnostic difficulties and discusses other medical conditions that can be mistaken for MS due to similar clinical, laboratory or radiological findings. PMID- 7784163 TI - [Astute in vivo observations discover anti-asthma medication]. AB - Will the new reductive biology write the book of revelation of all progress as concerns the pathophysiology and pharmacology of asthma? The early and recent medical history of anti-asthma drugs supports the possibility that exploratory in vivo research involving patients and disease-like test systems may "unexpectedly" provide leap discoveries in pathophysiology and pharmacology. New treatments based on defined molecular disease mechanisms will no doubt emerge. However, the future may also hold novel important anti-asthma drugs where the exact mode of action remains a challenge. Indeed, many aspects of the efficacies of the already long established anti-asthma drug principles have yet to be explained at the end organ, cellular and molecular levels. PMID- 7784164 TI - [Health and environment strategy in WHO]. PMID- 7784165 TI - [Preventive activities for the elderly--what happens after screening?]. AB - Preventive geriatric health care has become a regular part of geriatric health service in some of Norway's municipalities. There are many reports concerning the findings from screenings, but there is little material about the target group's experience with the subsequent intervention. This article describes the results from interviews with the elderly in three municipalities, concerning the perceived value of participating in geriatric screening. A random sample comprising 60 persons with a registered need of intervention was interviewed. Of the registered needs, intervention was implemented in 69 percent of the cases. In 65 percent of the cases the elderly person was satisfied with the intervention, five percent were dissatisfied and for 30 percent, the registration of a need for intervention had no practical significance. In 26 percent of the cases of registered need, the elderly person planned to seek assistance from the health/assistance services on his/her own. The most important reasons why intervention was not implemented were: the lack of a service to intervene in cases of loneliness and/or social isolation, and the lack of motivation on the part of the elderly to seek dental treatment. PMID- 7784166 TI - [Problem-based learning during surgery courses--good experiences with combination curriculum]. AB - Problem solving and critical thinking are important components of problem based learning (PBL). The driving forces are the students' interest, involvement and sense of responsibility. A curriculum comprising a combination of PBL and conventional instruction was introduced during the surgery course at Huddinge Hospital in the autumn term 1993. The results showed the level of knowledge attained by the students to be comparable with that attained under conventional instruction. The authors of the article conclude that good results can be obtained by introducing PBL in isolated sections of medical education within the framework of an otherwise traditional curriculum. PMID- 7784167 TI - [Society for homosexual physicians in Scandinavia]. PMID- 7784168 TI - Distamycin A and tallimustine inhibit TBP binding and basal in vitro transcription. AB - The antibiotic distamycin A is a DNA minor groove binding drug (MGB) that recognizes a stretch of at least four ATs. The alkylating benzoyl mustard derivative tallimustine (FCE 24517) has powerful anti-tumor activity. Using the electrophoretic mobility shift assay (EMSA) we determined that both compounds can prevent binding of TBP and, with 10-fold higher concentration, TBP-TFIIA (DA) and TBP-TFIIA-TFIIB (DAB) to a TATA box. Once formed, the DA and DAB complexes are more resistant to MGB challenge. Both drugs can inhibit basal in vitro transcription of a minimal TATA-containing promoter and similar concentrations are necessary for binding and transcriptional inhibition. Tallimustine shows strong selectivity by decreasing only correctly initiated transcripts. Even at high doses (20 microM), however, they cannot disturb a competent pre-initiation complex or Pol II progression. This functional in vitro model will provide a way to investigate the activity of sequence-specific DNA binding drugs with potential anti-viral and anti-tumour activity and to develop novel more selective compounds. PMID- 7784169 TI - Novel reagents for chemical cleavage at abasic sites and UV photoproducts in DNA. AB - Hot piperidine is often used to cleave abasic and UV-irradiated DNA at the sites of damage. It can inflict non-specific damage on DNA, probably because it is a strong base and creates significant concentrations of hydroxyl ions which can attack purines and pyrimidines. We show that several other amines can cleave abasic DNA at or near neutral pH without non-specific damage. One diamine, N,N' dimethylethylenediamine, efficiently cleaves abasic DNA at pH 7.4 by either beta- or beta,delta-elimination, depending on temperature. Using end-labelled oligonucleotides we show that cleavage depends mainly on elimination reactions, but that 4',5'-cyclization is also significant. This reagent also cleaves at photoproducts induced by UVC and UVB, producing the same overall pattern as piperidine, but with no non-specific damage. It should prove valuable in locating low levels of photoproducts in DNA, such as those induced by natural sunlight. PMID- 7784170 TI - Sequencing of an upstream region of the human HLA-DRA gene containing X' and Y' boxes. AB - In this paper we report the characterization of a newly sequenced 5' upstream region of the human HLA-DRA gene. We performed (i) search for transcription factor motifs, (ii) analysis of CpG display and observed/expected frequency ratios, (iii) search for regions homologous to the 5' upstream sequences of the murine EA gene, (iv) DNase I footprinting experiments and (v) electrophoretic mobility shift assays. Our results demonstrate the existence, in the HLA-DRA gene, of Y' and X' boxes highly homologous to the Y and X boxes present in MHC class II genes, but oriented in the opposite direction. These Y' and X' boxes have been conserved during the molecular evolution of both human HLA-DRA and murine EA genes. DNase I footprinting and gel retardation experiments suggest that the X' and Y' boxes of the HLA-DRA upstream gene region are specifically recognized by nuclear proteins that also bind to the X and Y boxes of the HLA-DRA proximal promoter, respectively. PMID- 7784171 TI - Regulation of the Saccharomyces cerevisiae DNA repair gene RAD16. AB - The RAD16 gene product has been shown to be essential for the repair of the silenced mating type loci [Bang et al. (1992) Nucleic Acids Res. 20, 3925-3931]. More recently we demonstrated that the RAD16 and RAD7 proteins are also required for repair of non-transcribed strands of active genes in Saccharomyces cerevisiae [Waters et al. (1993) Mol. Gen. Genet. 239, 28-32]. We have studied the regulation of the RAD16 gene and found that the RAD16 transcript levels increased up to 7-fold upon UV irradiation. Heat shock at 42 degrees C also results in elevated levels of RAD16 mRNA. In sporulating MAT alpha/MATa diploid cells RAD16 mRNA is also induced. The basal level of the RAD16 transcript is constant during the mitotic cell cycle. G1-arrested cells show normal induction of RAD16 mRNA upon UV irradiation demonstrating that the induction is not a secondary consequence of G2 cell cycle arrest following UV irradiation. However, in cells arrested in G1 the induction of RAD16 mRNA after UV irradiation is not followed by a rapid decline as occurs in normal growing cells suggesting that the down regulation of RAD16 transcription is dependent on progression into the cell cycle. PMID- 7784172 TI - A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. AB - A number of proteins have been rendered functionally oestrogen-dependent by fusion with the hormone-binding domain of the oestrogen receptor. There are, however, several significant disadvantages with such fusion proteins. First, their use in cells in vitro requires phenol red-free medium and laborious stripping of steroid hormones from serum in order to avoid constitutive activation. Secondly, control of oestrogen receptor fusion proteins in vivo is precluded by high endogenous levels of circulating oestrogens. Thirdly, the hormone-binding domain of the oestrogen receptor functions as a hormone-dependent transcriptional activation domain making interpretation of fusions with transcription factors problematical. In order to overcome these drawbacks we have used a transcriptionally inactive mutant of the murine oestrogen receptor which is unable to bind oestrogen yet retains normal affinity for the synthetic ligand, 4-hydroxytamoxifen. When the hormone-binding domain of this mutant oestrogen receptor is fused to the C-terminus of the c-Myc protein, Myc-induced proliferation and apoptosis in fibroblasts becomes dependent on 4 hydroxytamoxifen, but remains refractory to 17 beta-oestradiol. PMID- 7784174 TI - The processing of macronuclear-destined DNA sequences microinjected into the macronuclear anlagen of the hypotrichous ciliate Stylonchia lemnae. AB - We describe the construction of a vector carrying the micronuclear versions of two macronuclear DNA molecules, one of which was modified by the insertion of a polylinker sequence. This vector was injected into the polytene chromosomes of the developing macronucleus of Stylonychia and its processing during further macronuclear development and its fate in the mature macronucleus were analyzed. In up to 30% of injected cells the modified macronuclear DNA sequence could be detected. While the internal eliminated sequences (IES) present in the macronuclear precursor DNA sequence are still retained in the mature macronucleus, the modified macronuclear DNA sequence is correctly cut out from the vector, telomeres are added de novo and it is stably retained in the macronucleus during vegetative growth of the cells. This vector system represents an experimental system that allows the identification of DNA sequences involved in the processing of macronuclear DNA sequences during macronuclear development. PMID- 7784175 TI - A trigonal form of the idarubicin:d(CGATCG) complex; crystal and molecular structure at 2.0 A resolution. AB - The X-ray crystal structure of the complex between the anthracycline idarubicin and d(CGATCG) has been solved by molecular replacement and refined to a resolution of 2.0 A. The final R-factor is 0.19 for 3768 reflections with Fo > or = 2 sigma (Fo). The complex crystallizes in the trigonal space group P31 with unit cell parameters a = b = 52.996(4), c = 33.065(2) A, alpha = beta = 90 degree, gamma = 120 degree. The asymmetric unit consists of two duplexes, each one being complexed with two idarubicin drugs intercalated at the CpG steps, one spermine and 160 water molecules. The molecular packing underlines major groove major groove interactions between neighbouring helices, and an unusually low value of the occupied fraction of the unit cell due to a large solvent channel of approximately 30 A diameter. This is the first trigonal crystal form of a DNA anthracycline complex. The structure is compared with the previously reported structure of the same complex crystallizing in a tetragonal form. The geometry of both the double helices and the intercalation site are conserved as are the intramolecular interactions despite the different crystal forms. PMID- 7784173 TI - A novel initiator regulates expression of the nontissue-specific helix-loop-helix gene ME1. AB - The mouse ME1 gene (HEB, REB and GE1, homologues in human, rat and chick, respectively) is a member of the nontissue-specific helix-loop-helix (HLH) gene family that includes E2A, E2-2 and Drosophila daughterless. We have examined the factors that control ME1 gene expression. ME1 is a single copy gene that spans > or = 150 kb of DNA and contains > 10 exons. Transcription was directed by an unusual initiator element that contained a 13 bp poly d(A) tract flanked by palindromic and inverted repeat sequences. Both RNase protection and primer extension analyses mapped the ME1 transcriptional start site to the center of the 13 bp poly d(A) tract. The ME1 initiator and its proximal sequences were required for promoter activity, supported basal levels of transcription, and contributed to cell type-specific gene expression. Other cis-elements utilized by the TATA less ME1 promoter included a cluster of Sp1 response elements, E-boxes and a strong repressor. Collectively, our results suggest that the ME1 initiator and other cis-elements in the proximal promoter play an important role in regulating ME1 gene expression. PMID- 7784176 TI - A gene-type-specific enhancer regulates the carbamyl phosphate synthetase I promoter by cooperating with the proximal GAG activating element. AB - The rat carbamyl phosphate synthetase I gene is expressed in two cell types: hepatocytes and epithelial cells of the intestinal mucosa. The proximal promoter contains a single activating element, GAG, two repressor elements (sites I and III) and an anti-repressor element (site II). Although these elements together exhibit the potential for complex regulation, they are unable to confer tissue specific promoter activity. Here we have identified a cell-type-specific enhancer that lies 10 kilobases upstream of the promoter. Unexpectedly, the enhancer also functioned in a gene-type-specific manner. The enhancer stimulated promoter activity exclusively through the proximal GAG element. Abrogation of GAG, either directly by mutation of GAG or indirectly by sites I and III repressors, abolished enhancer activation. Conversely, activation of the heterologous thymidine kinase promoter by the enhancer required the introduction of GAG. The requirement for GAG, therefore, functions to constrain the enhancer to a specific target promoter. PMID- 7784177 TI - Physical and functional interaction of the Epstein-Barr virus BZLF1 transactivator with the retinoic acid receptors RAR alpha and RXR alpha. AB - Epstein-Barr virus (EBV) reactivation, indicated by induction of EBV early antigens from latently infected lymphoid cell lines by phorbol esters, is inhibited by retinoic acid (RA). Viral reactivation, which is triggered by the immediate-early BZLF-1 (Z) viral gene product, is repressed by retinoic acid receptors (RARs) RAR alpha and RXR alpha. These proteins negatively regulate Z mediated transactivation of the promoter for an EBV early gene product, early antigen-diffuse (EaD). Here we confirm a direct physical interaction between the AP1-like protein Z and RXR alpha and map the domains of interaction in the Z protein and RXR alpha. The domain required for homodimerization of Z is separate from that required for its interaction with RXR alpha. Z also has the effect of repressing activation of an RAR-responsive cellular promoter (BRE). Point mutants in the dimerization domain of Z unable to interact with RXR alpha do not repress RXR alpha-mediated transactivation of BRE, the promoter for RAR beta, which suggests that interaction between the two proteins is required for this repressor effect. The domain of RXR alpha required for interaction with Z has been mapped, and is again separate from that required for homodimerization. These results indicate that a 'cross-coupling' or direct interaction between Z and RAR alpha and RXR alpha can modulate the reactivation of latent EBV infection and suggest that, reciprocally, the viral protein Z may influence cellular regulatory pathways. PMID- 7784178 TI - Genetic and molecular analysis of the tRNA-tufB operon of the myxobacterium Stigmatella aurantiaca. AB - The tufB gene, encoding elongation factor Tu (EF-Tu), from the myxobacterium Stigmatella aurantiaca was cloned and sequenced. It is preceded by four tRNA genes, the first ever described in myxobacteria. The tRNA synthesized from these genes and the general organization of the locus seem identical to that of Escherichia coli, but differences of potential importance were found in the tRNA sequences and in the intergenic regions. The primary structure of EF-Tu was deduced from the tufB DNA sequence. The factor is composed of 396 amino acids, with a predicted molecular mass of 43.4 kDa, which was confirmed by expression of tufB in maxicells. Sequence comparisons between S.aurantiaca EF-Tu and other bacterial homologues from E.coli, Salmonella typhimurium and Thermus thermophilus displayed extensive homologies (75.9%). Among the variable positions, two Cys residues probably involved in the temperature sensitivity of E.coli and S.typhimurium EF-Tu are replaced in T.thermophilus and S.aurantiaca EF-Tu. Since two or even three tuf genes have been described in other bacterial species, the presence of multiple tuf genes was sought for. Southern and Northern analysis are consistent with two tuf genes in the genome of S.aurantiaca. Primer extension experiments indicate that the four tRNA genes and tufB are organized in a single operon. PMID- 7784180 TI - Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. AB - The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function. PMID- 7784179 TI - Cleavage of the HIV replication primer tRNALys,3 in human cells expressing bacterial anticodon nuclease. AB - Anticodon nuclease is a bacterial restriction enzyme directed against tRNA(Lys). We report that anticodon nuclease also cleaves mammalian tRNA(Lys) molecules, with preference and site specificity shown towards the natural substrate. Expression of the anticodon nuclease core polypeptide PrrC in HeLa cells from a recombinant vaccinia virus elicited cleavage of intracellular tRNA(Lys),3. The data justify an inquiry into the possible application of anticodon nuclease as an inhibitor of tRNA(Lys),3-primed HIV replication. They also indicate that the anticodon region of tRNA(Lys) is a substrate recognition site and suggest that PrrC harbors the enzymatic activity. PMID- 7784182 TI - Cloning and functional analysis of the TATA binding protein from Sulfolobus shibatae. AB - Archaea (formerly archaebacteria) comprise a domain of life that is phylogenetically distinct from both Eucarya and Bacteria. Here we report the cloning of a gene from the Archaeon Sulfolobus shibatae that encodes a protein with strong homology to the TATA binding protein (TBP) of eukaryotes. Sulfolobus shibatae TBP is, however, almost as diverged from other archaeal TBPs that have been cloned as it is from eukaryotic TBPs. DNA binding studies indicate that S.shibatae TBP recognizes TATA-like A-box sequences that are present upstream of most archaeal genes. By quantitatively immunodepleting S.shibatae TBP from an in vitro transcription system, we demonstrate that Sulfolobus RNA polymerase is capable of transcribing the 16S/23S rRNA promoter weakly in the absence of TBP. Most significantly, we show that addition of recombinant S.shibatae TBP to this immunodepleted system leads to transcriptional stimulation and that this stimulation is dependent on the A-box sequence of the promoter. Taken together, these findings reveal fundamental similarities between the transcription machineries of Archaea and eukaryotes. PMID- 7784181 TI - Modular structural elements in the replication origin region of Tetrahymena rDNA. AB - Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophila identified a potential initiation zone in the 5'NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res. 22, 2479-2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryotic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites in super-coiled plasmid DNA were localized within the major DUE-like element predicted by thermodynamic analyses. Three restriction fragments of the 5'NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresis on polyacrylamide gels. Restriction fragments containing the 5'NTS region bound Tetrahymena nuclear matrices in an in vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix in vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila, chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication. PMID- 7784183 TI - Presence of negative torsional tension in the promoter region of the transcriptionally poised dihydrofolate reductase gene in vivo. AB - DNA topology has been suggested to play an important role in the process of transcription. Negative torsional tension has been shown to stimulate both pre initiation complex formation and promoter clearance on plasmid DNA in vitro. We recently showed that genomic DNA in human cells contains localized torsional tension. In the present study we have further characterized and mapped torsional tension in the dihydrofolate reductase (DHFR) gene in Chinese hamster ovary (CHO) cells and investigated the effects of differential rates of transcription on the magnitude and location of this tension. Using psoralen photo-cross-linking in conjunction with X-irradiation, we found that relaxable psoralen hypersensitivity was specifically localized to the promoter region of the serum-regulated DHFR gene in serum-stimulated, but not in serum-starved, cells. Moreover, this hypersensitivity did not appear to be caused by transcription elongation, since it persisted in cells in which transcription of the DHFR gene had been reduced by the transcription inhibitor 5,6-dichloro-1-beta-D-ribofurano-sylbenzimidazole (DRB). We suggest that the generation of negative torsional tension in DNA may play an important role in gene regulation by poising genes for transcription. PMID- 7784185 TI - Ultrasensitive hybridization analysis using fluorescence correlation spectroscopy. AB - The hybridization of fluorescently tagged 18mer deoxyribonucleotides with complementary DNA templates was analysed by fluorescence correlation spectroscopy (FCS) in a droplet under an epi-illuminated fluorescence microscope at the level of single molecules. The interaction can be monitored by the change in the translational diffusion time of the smaller (18mer) primer when binding to the bigger (7.5 kb) DNA containing the complementary sequence. The hybridization process in the presence of template M13mp18 ssDNA was monitored in a small volume (2 x 10(-16)I) at various temperatures. The Arrhenius plot of the association rate constant shows that the activation energy was 38.8 kcal/mol, but the hybridization process may involve several components. The titration experiment suggested that approximately 2 primers can be associated with one template DNA at 40 degrees C. Results of a simple homology search for the sequences complementary to the primer indicate the existence of additional sites of lower specificity. PMID- 7784184 TI - Function of the upstream hypersensitive sites of the chicken beta-globin gene cluster in mice. AB - We have shown previously that the chicken beta A-globin gene, with its 3' enhancer, is expressed in a copy number-dependent manner in transgenic mice. The expression level was low but increased approximately 6-fold upon inclusion of 11 kb of upstream DNA containing four DNase I hypersensitive sites. To study the effect of the individual upstream hypersensitive sites on transgene expression, we produced lines of mice in which the individual upstream sites were linked to the beta A gene and enhancer. RNA levels were measured in blood from adult animals. With each of these four constructs, the level of transgene RNA per DNA copy varied over a > 20-fold range. These data suggest that addition of a hypersensitive site to the beta A-globin/enhancer region abrogates its position independent expression. The average beta A-globin expression per copy in the lines carrying an upstream site was comparable with that in lines without an upstream site. Thus, no single upstream hypersensitive site accounts for the higher level of beta A-globin expression seen in mice containing the complete upstream region. We had shown previously that control of the chicken beta-globin cluster is distributed between at least two regions, the beta A/epsilon enhancer and the upstream region. Our current results suggest that the control mediated by the upstream DNA is itself distributed and is not due to a single hypersensitive site. PMID- 7784187 TI - Solution structure of a nucleic acid photoproduct of deoxyfluorouridylyl-(3'-5') thymidine monophosphate (d-FpT) determined by NMR and restrained molecular dynamics: structural comparison of two sequence isomer photoadducts (d-U5p5T and d-T5p5U). AB - Acetone-sensitized irradiation using UV-B (sun lamp, lambda max = 313 nm) of deoxyfluorouridylyl-(3'-5')-thymidine monophosphate (d-FpT, F = fluorouracil), produces two major photoproducts, the cis-syn cyclobutane-type photodimer and a defluorinated (5-5) photoadduct, d-U5p5T. Product distribution is dependent on the pH of the irradiation solution, as was the case of irradiated d-TpF. At high pH (8-10) the (5-5) photoadduct is the major photoproduct. Irradiation of d-FpT shows a much faster photodegradation rate than the sequence isomer d-TpF. Multinuclear NMR experiments establish the formation of (5-5) covalent bonding between the C5 (d-U5p-, where the fluorine had been) and the C5 (-p5T) and the C6 (-p5T) acquires an OH group. NOE interproton distances and dihedral angles derived from J coupling analysis are constrained to refine model structures of d U5p5T in restrained molecular dynamics calculations. The resultant structures obtained show 5S-6S as the most chiralities of the C5 and C6 atoms of the thymine, which is the opposite chirality to the corresponding atoms in the sequence isomer d-T5p5U. The orientation of the C5 substituents (-p5T fragment), the CH3 and the uracil are pseudo-axial and pseudo-equatorial respectively. Glycosidic angles are in the anti regions for both the d-U5p- and -p5T residues. Averaged backbone conformations of the two photoadducts, d-U5p5T and d-T5p5U, are similar, although the overall structure of d-U5p5T appears much more flexible than that of d-T5p5U. In particular, the sugar conformations of the 5'-end residues show a remarkable difference in flexibility. PMID- 7784186 TI - Polyamines alter sequence-specific DNA-protein interactions. AB - The polyamines are abundant biogenic cations implicated in many biological processes. Despite a plethora of evidence on polyamine-induced DNA conformational changes, no thorough study of their effects on the activities of sequence specific DNA binding proteins has been performed. We describe the in vitro effects of polyamines on the activities of purified, representative DNA-binding proteins, and on complex protein mixtures. Polyamines at physiological concentrations enhance the binding of several proteins to DNA (e.g. USF, TFE3, Ig/EBP, NF-IL6, YY1 and ICP-4, a herpes simplex virus gene regulator), but inhibit others (e.g. Oct-1). The degree of enhancement correlates with cationic charge; divalent putrescine is ineffective whereas tetravalent spermine is more potent than trivalent spermidine. Polyamine effects on USF and ICP-4 result from increased rate of complex formation rather than a decreased rate of dissociation. DNAse I footprint analysis indicated that polyamines do not alter DNA-protein contacts. Polyamines also facilitate formation of complexes involving binding of more than one protein on a DNA fragment. PMID- 7784188 TI - Dehydrating agents sharply reduce curvature in DNAs containing A tracts. AB - The structural basis of DNA curvature remains elusive, because models for curvature based on crystallographic structures of molecules containing A tracts do not agree with any of the models for sequence-directed curvature based on solution studies. Here we demonstrate that the difference is probably due to MPD (2-methyl-2,4-pentanediol), the dehydrating agent commonly used in crystallography. One characteristic signature of curved DNA molecules is that they run anomalously slowly on polyacrylamide gels, appearing to be larger than they actually are. The gel anomalies of three curved DNAs from trypanosome kinetoplast minicircles drop monotonically with increasing MPD concentration, indicating that MPD straightens molecules that are curved in aqueous solution. This is not due to some non-specific effect of MPD on poly(dA) or polypurine tracts, because control molecules containing dA70 and dG43 run normally over the full range of MPD concentrations. Circular dichroism spectra are not affected by MPD, ruling out a conformational change to a structure outside the B-DNA family. The effect is not due to MPD-induced changes in phasing of the curved sequences, because MPD has virtually no effect on the linking numbers of relaxed plasmids containing either curved sequences or dA70. At the concentrations of MPD used in X-ray crystallography, the curvature of DNAs containing A tracts is substantially lower than in solution, which probably explains the ongoing discrepancies between the crystallographic results and models based on solution studies. PMID- 7784190 TI - Integrative modification of YAC clones in a 96-well microplate format. PMID- 7784189 TI - Multiple protein-DNA interactions over the yeast HSC82 heat shock gene promoter. AB - We have utilized DNase I and micrococcal nuclease (MNase) to map the chromatin structure of the HSC82 heat shock gene of Saccharomyces cerevisiae. The gene is expressed at a high basal level which is enhanced 2-3-fold by thermal stress. A single, heat-shock invariant DNase I hypersensitive domain is found within the HSC82 chromosomal locus; it maps to the gene's 5' end and spans 250 bp of promoter sequence. DNase I genomic footprinting reveals that within this hypersensitive region are four constitutive protein-DNA interactions. These map to the transcription initiation site, the TATA box, the promoter-distal heat shock element (HSE1) and a consensus GRF2 (REB1/Factor Y) sequence. However, two other potential regulatory sites, the promoter-proximal heat shock element (HSE0) and a consensus upstream repressor sequence (URS1), are not detectably occupied under either transcriptional state. In contrast to its sensitivity to DNAase I, the nucleosome-free promoter region is relatively protected from MNase; the enzyme excises a stable nucleoprotein fragment of approximately 210 bp. As detected by MNase, there are at least two sequence-positioned nucleosomes arrayed 5' of the promoter; regularly spaced nucleosomes exhibiting an average repeat length of 160-170 bp span several kilobases of both upstream and downstream regions. Similarly, the body of the gene, which exhibits heightened sensitivity to DNase I, displays a nucleosomal organization under both basal and induced states, but these nucleosomes are not detectably positioned with respect to the underlying DNA sequence and may be irregularly spaced and/or structurally altered. We present a model of the chromatin structure of HSC82 and compare it to one previously derived for the closely related, but differentially regulated, HSP82 heat shock gene. PMID- 7784191 TI - Differential display by PCR: novel findings and applications. PMID- 7784192 TI - Combinatorial libraries by cassette mutagenesis. PMID- 7784193 TI - arg3+, a new selection marker system for Schizosaccharomyces pombe: application of ura4+ as a removable integration marker. PMID- 7784194 TI - Selection of a sublibrary enriched for a chromosome from total human bacterial artificial chromosome library using DNA from flow sorted chromosomes as hybridization probes. PMID- 7784195 TI - Site-specific initiation of DNA replication within the non-transcribed spacer of Physarum rDNA. AB - Physarum polycephalum rRNA genes are found on extrachromosomal 60 kb linear palindromic DNA molecules. Previous work using electron microscope visualization suggested that these molecules are duplicated from one of four potential replication origins located in the 24 kb central non-transcribed spacer [Vogt and Braun (1977) Eur. J. Biochem., 80, 557-566]. Considering the controversy on the nature of the replication origins in eukaryotic cells, where both site-specific or delocalized initiations have been described, we study here Physarum rDNA replication by two dimensional agarose gel electrophoresis and compare the results to those obtained by electron microscopy. Without the need of cell treatment or enrichment in replication intermediates, we detect hybridization signals corresponding to replicating rDNA fragments throughout the cell cycle, confirming that the synthesis of rDNA molecules is not under the control of S phase. The patterns of replication intermediates along rDNA minichromosomes are consistent with the existence of four site-specific replication origins, whose localization in the central non-transcribed spacer is in agreement with the electron microscope mapping. It is also shown that, on a few molecules, at least two origins are active simultaneously. PMID- 7784196 TI - Protein-DNA interactions in soluble telosomes from Saccharomyces cerevisiae. AB - Telomeric DNA in Saccharomyces is organized into a non-nucleosomal chromatin structure called the telosome that can be released from chromosome ends in soluble form by nuclease digestion (Wright, J. H., Gottschling, D. E. and Zakian, V. A. (1992) Genes Dev. 6, 197-210). The protein-DNA interactions of soluble telosomes were investigated by monitoring isolated telomeric DNA fragments for the retention of bound protein using both gel mobility shift and nitrocellulose filter-binding assays. Telosomal proteins remained associated with telomeric DNA at concentrations of ethidium bromide that dissociated nucleosomes. The protein DNA interactions in the yeast telosome were also disrupted by much lower salt concentrations than those known to disrupt either the interactions of ciliate terminus-binding proteins with telomeric DNA or the interactions of histones with DNA in nucleosomes. Taken together, these data corroborate previously published nuclease mapping data indicating that telosomes are distinct in structure from conventional nucleosomes. These data also indicate that yeast do not possess telomere binding proteins similar to those detected in ciliates that remain tightly bound to telomeric DNA even in high salt. In addition, the characteristic gel mobility shift of soluble telosomes could be mimicked by complexes formed in vitro with yeast telomeric DNA and recombinant Rap1p suggesting that Rap1p, a known component of soluble yeast telosomes (Wright, J. H., Gottschling, D. E. and Zakian, V. A. (1992) Genes Dev. 6, 197-210; Conrad, M. N., Wright, J. H., Wolf, A. J. and Zakian, V. A. (1990) Cell 63, 739-750), is likely to be the major structural protein bound directly to yeast telomeric DNA. PMID- 7784197 TI - Defining a novel cis element in the 3'-untranslated region of mammalian ribonucleotide reductase component R2 mRNA: role in transforming growth factor beta 1 induced mRNA stabilization. AB - Ribonucleotide reductase R2 gene expression is elevated in BALB/c 3T3 fibroblasts treated with transforming growth factor beta 1. We investigated the possibility that the 3'-UTR of ribonucleotide reductase R2 mRNA contains regulatory information for TGF-beta 1 induced message stability. Using end-labeled RNA fragments in gel shift assays and UV cross-linking analyses, we detected in the 3'-UTR a novel 9 nucleotide (nt) cis element, 5'-GAGUUUGAG-3' site, which interacted specifically with a cytosolic protease sensitive factor to form a 75 kDa complex. The cis element protein binding activity was inducible and markedly up-regulated cross-link 4 h after TGF-beta 1 treatment of mouse BALB/c 3T3 cells. Other 3'-UTRs [IRE, GM-CSF, c-myc and homopolymer (U)] were poor competitors to the cis element with regard to forming the TGF-beta 1 dependent RNA-protein complex. However, the cis element effectively competed out the formation of the R2 3'-UTR protein complex. Cytosolic extracts from a variety of mammalian cell lines (monkey Cos7, several mouse fibrosarcomas and human HeLa S3) demonstrated similar TGF-beta 1 dependent RNA-protein band shifts as cell extract from BALB/c 3T3 mouse fibroblasts. Binding was completely prevented by several different mutations within the cis element, and by substitution mutagenesis, we were able to predict the consensus sequences, 5'-GAGUUUNNN-3' and 5'-NNNUUUGAG-3' for optimal protein binding. These results support a model in which the 9 nt region functions in cis to destabilize R2 mRNA in cells; and upon activation, a TGF-beta 1 responsive protein is induced and interacts with the 9 nt cis element in a mechanism that leads to stabilization of the mRNA. This appears to be the first example of a mRNA binding site that is involved in TGF-beta 1-mediated effects. PMID- 7784198 TI - The lytic replicon of bacteriophage P1 is controlled by an antisense RNA. AB - The lytic replicon of phage P1 is used for DNA replication during the lytic cycle. It comprises about 2% of the P1 genome and contains the P1 C1 repressor controlled operator-promoter element Op53.P53 and the kilA and the repL genes, in that order. Transcription of the lytic replicon of P53 and synthesis of the product of repL, but not kilA, are required for replicon function. We have identified an additional promoter, termed P53as (antisense), at the 5'-end of the kilA gene from which a 180 base transcript is constitutively synthesized and in the opposite direction to the P53 transcript. By using a promoter probe plasmid we show that transcription from P53 is strongly repressed by the C1 repressor, whereas that of P53as remains unaffected. Accordingly, the C1 repressor inhibits binding of Escherichia coli RNA polymerase to P53, but not to P53as, as shown by electron microscopy. Under non-repressed conditions transcription from P53 appears to be inhibited by P53as activity and vice versa. An inhibitory effect of P53as on the P1 lytic replicon was revealed by the construction and characterization of a P53as promoter-down mutant. Under non-repressed conditions transcription of repL and, as a consequence, replication of the plasmid is strongly enhanced when P53as is inactive. The results suggest a regulatory role for P53as on the P1 lytic replicon. PMID- 7784199 TI - Transcription activation of yeast ribosomal protein genes requires additional elements apart from binding sites for Abf1p or Rap1p. AB - All ribosomal protein (rp) gene promoters from Saccharomyces cerevisiae studied so far contain either (usually two) binding sites for the global gene regulator Rap1p or one binding site for another global factor, Abf1p. Previous analysis of the rpS33 and rpL45 gene promoters suggested that apart from the Abf1 binding site, additional cis-acting elements play a part in transcription activation of these genes. We designed a promoter reconstruction system based on the beta glucuronidase reporter gene to examine the role of the Abf1 binding site and other putative cis-acting elements in promoting transcription. An isolated Abf1 binding site turned out to be a weak activating element. A T-rich sequence derived from the rpS33 proximal promoter was found to be stronger, but full transcription activation was only achieved by a combination of these elements. Both in the natural rpL45 promoter and in the reconstituted promoter, a Rap1 binding site could functionally replace the Abf1 binding site. Characteristic rp gene nutritional control of transcription, evoked by a carbon source upshift or by nitrogen re-feeding to nitrogen starved cells, could only be mediated by the combined Abf1 (or Rap1) binding site and T-rich element and not by the individual elements. These results demonstrate that Abf1p and Rap1p do not activate rp genes in a prototypical fashion, but rather may serve to potentiate transcription activation through the T-rich element. PMID- 7784200 TI - The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. AB - Previous studies have shown that the yeast Candida albicans encodes a unique seryl-tRNA(CAG) that should decode the leucine codon CUG as serine. However, in vitro translation of several different CUG-containing mRNAs in the presence of this unusual seryl-tRNA(CAG) result in an apparent increase in the molecular weight of the encoded polypeptides as judged by SDS-PAGE even though the molecular weight of serine is lower than that of leucine. A possible explanation for this altered electrophoretic mobility is that the CUG codon is decoded as modified serine in vitro. To elucidate the nature of CUG decoding in vivo, a reporter system based on the C. albicans gene (RBP1) encoding rapamycin-binding protein (RBP), coupled to the promoter of the C. albicans TEF3 gene, was utilized. Sequencing and mass-spectrometry analysis of the recombinant RBP expressed in C. albicans demonstrated that the CUG codon was decoded exclusively as serine while the related CUU codon was translated as leucine. A database search revealed that 32 out of the 65 C. albicans gene sequences available have CUG codons in their open reading frames. The CUG-containing genes do not belong to any particular gene family. Thus the amino acid specified by the CUG codon has been reassigned within the mRNAs of C. albicans. We argue here that this unique genetic code change in cellular mRNAs cannot be explained by the 'Codon Reassignment Theory'. PMID- 7784201 TI - Prokaryotic ribosomes recode the HIV-1 gag-pol-1 frameshift sequence by an E/P site post-translocation simultaneous slippage mechanism. AB - The mechanism favoured for -1 frameshifting at typical retroviral sites is a pre translocation simultaneous slippage model. An alternative post-translocation mechanism would also generate the same protein sequence across the frameshift site and therefore in this study the strategic placement of a stop codon has been used to distinguish between the two mechanisms. A 26 base pair frameshift sequence from the HIV-1 gag-pol overlap has been modified to include a stop codon immediately 3' to the heptanucleotide frameshift signal, where it often occurs naturally in retroviral recoding sites. Stop codons at the 3'-end of the heptanucleotide sequence decreased the frame-shifting efficiency on prokaryote ribosomes and the recording event was further depressed when the levels of the release factors in vivo were increased. In the presence of elevated levels of a defective release factor 2, frameshifting efficiency in vivo was increased in the constructs containing the stop codons recognized specifically by that release factor. These results are consistent with the last six nucleotides of the heptanucleotide slippery sequence occupying the ribosomal E and P sites, rather than the P and A sites, with the next codon occupying the A site and therefore with a post-translocation rather than a pre-translocation -1 slippage model. PMID- 7784203 TI - Modified nucleotides reveal the indirect role of the central base pairs in stabilizing the lac repressor-operator complex. AB - Guanine residues in the lac operator were replaced by 2-aminopurine or purine analogues, pairing the modified nucleotides with C. The observed equilibrium dissociation constants for lac repressor binding to substituted operators were measured in 10 mM Tris, 150 mM KCl, 0.1 mM EDTA, 0.1 mM DTE, pH 7.6 at 25 degrees C. These measurements revealed five positions that destabilized the complex when substituted with either analogue. Two positions, which are related by a 2-fold symmetry, are in the major groove of the operator thought to directly interact with the protein. Three sites were in the central region of the operator. A purine analogue at a sixth site perturbed the local DNA structure and destabilized the complex. Alkylation interference experiments of the 2 aminopurine substituted operators demonstrated that, of the five affected, two substitutions displayed altered phosphate interference patterns at the phosphate adjacent to the substituted base. For these operators, complex formation was measured in different concentrations of KCl to assess the contribution of counterion release to the bimolecular process. The results indicated that both complexes were similar to wild-type, although minor changes were observed. The Kobs of the complex was then measured when 2-aminopurine or purine analogues were paired with uracil nucleotide, a base pair that serves to stabilize the DNA. The introduction of the new base pairs revealed two effects on the bimolecular interaction. For those operator sites that are thought to perturb the interaction directly, the affinity of the complex was weakened to levels observed for the singly-substituted operators. In contrast, the nucleotides of 2-aminopurine paired with uracil positioned in the central region of the operator served to enhance the stability of the complex. The purine-uracil base pair substitution on the other hand had a significant destabilizing effect on the interaction. We propose that the central base pairs modulate binding of the complex by altering the intrinsic properties of the DNA. Two specific attributes are required to achieve the lowest free energy of interaction. The DNA must have two interstrand hydrogen bonds to stabilize the duplex and it must have properties associated with directional bending or unwinding. This analysis does not rule out contributions by direct interactions between the protein and the central region of the operator but underscores how indirect effects play a major role in complex formation in this system. PMID- 7784202 TI - A Sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo. AB - The direct intramuscular delivery of naked plasmid DNA has been demonstrated to allow expression of encoded heterologous genes in the target myocytes. The method has been employed to elicit immunization based upon delivery of antigen encoding plasmid DNA. For application in the context of achieving anti-tumor immunization against antigenic transforming oncoproteins, delivery of plasmid DNAs encoding these molecules would create significant potential safety hazards. As an alternative to DNA polynucleotide vectors, we explored the utility of mRNA vehicles for inducing foreign gene expression in muscle cells in vivo. Synthetic reporter-gene encoding mRNA transcripts were derived for this analysis. The Sindbis virus vector was also used to derive luciferase mRNA transcripts which possessed self-replication capacity. In these studies, it could be shown that the replicative vector was capable of directing significantly elevated levels of reporter gene expression in myocytes compared to a non-replicative mRNA species. In addition, the replicative species was capable of achieving significantly prolonged levels of in vivo gene expression compared to non-replicative mRNA. Both of these characteristics will make replicative mRNA vectors of utility for polynucleotide-based immunization protocols. PMID- 7784205 TI - The Escherichia coli MelR transcription activator: production of a stable fragment containing the DNA-binding domain. AB - A set of nested deletions has been made in the Escherichia coli melR gene, encoding the MelR transcription activator protein. Expression of the resulting melR derivatives led to the production of nine MelR proteins with N-terminal deletions of different lengths. The properties of the shortened proteins have been studied both in vivo and in vitro. None of the truncated proteins activate transcription from the E.coli melAB promoter but three; MelR220, MelR183 and MelR173, inhibit activation of the melAB promoter by chromosomally-encoded full length MelR. In gel retardation assays, both MelR183 and MelR173 clearly retard DNA fragments carrying the melAB promoter. MelR173 has been overproduced in a T7 expression system and shown to be stable in vivo for up to 2 h. DNAase I footprinting assays of partially purified protein show that it binds to the melAB promoter, protecting the same sites as the full-length protein. This fragment may be suitable for further structure/function studies of this class of transcription activator. PMID- 7784204 TI - Role for the highly conserved region of domain IV of 23S-like rRNA in subunit subunit interactions at the peptidyl transferase centre. AB - The function of the highly conserved and accessible region of domain IV of 23S rRNA (positions 1900-1981 in Escherichia coli 23S rRNA) was investigated by subjecting it to a random mutagenesis procedure that produced single-site mutations efficiently. Nine single-site mutants were selected that were recessive lethal. High levels of mutated 23S rRNA were expressed in E. coli and extracted ribosomes were investigated for their content of mutated rRNA. The peptidyl transferase activity of the ribosomes was also estimated using a newly developed method involving selective inhibition of chromosome-encoded ribosomes by clindamycin. Two of the mutants, U1940A and U1955G, yielded 50S subunits that were defective in subunit-subunit association but active in peptidyl transferase activity and five, U1926C, U1946C, U1979C, U1982A and G1984A, produced 50S subunits that were defective in both subunit-subunit interactions and peptidyl transferase activity. We infer that the large conserved rRNA region generates a complex structure that plays an essential role in maintaining and modulating subunit-subunit interactions and argue that its involvement in the peptidyl transferase centre is secondary, possibly involving the correct alignment of protein L2. PMID- 7784206 TI - Direct measurement via phage titre of the dissociation constants in solution of fusion phage-substrate complexes. AB - Studies of interactions between filamentous fusion phage particles and protein or nucleic acid molecules have gained increasing importance with recent successes of screening techniques based upon random phage display libraries (biopanning). Since a number of different phage are usually obtained by biopanning, it is useful to compare quantitatively the binding affinities of individual phage for the substrate used for selection. A procedure is described for determination of relative dissociation constants (KdRel) between filamentous phage carrying peptide fusions to the coat protein gpIII and substrates in solution. This novel method is based on the measurement of phage titres. Phage selected from a random fusion phage library for binding to a monoclonal antibody or a viral structural protein exhibited KdRel values in the nanomolar and micromolar ranges for their respective substrates, thus validating the method over a wide range of binding affinities. PMID- 7784207 TI - Transcriptional activation by the orphan nuclear receptor ARP-1. AB - ARP-1 is a ubiquitous orphan nuclear receptor that binds to a site (site A) in the apolipoprotein AI (apoAI) liver-specific enhancer and represses its transcriptional activity in hepatoblastoma HepG2 cells. Electrophoretic mobility shift analysis of HepG2 cell nuclear extracts showed that in addition to ARP-1, site A also binds the orphan nuclear receptors Ear-2 and HNF-4. In in vitro transcription assays, Hela cell nuclear extracts which contain ARP-1 had no effect on transcription from a basal promoter linked to multiple copies of site A. However, supplementation of these extracts with excess amounts of recombinant ARP-1 resulted in significant stimulation. Supplementation of the extracts with purified polypeptides representing fusions between the ARP-1 N- or C-terminal domains and the yeast activator GAL4 DNA binding domain also stimulated transcription from a basal promoter linked to multiple GAL4 DNA binding sites. Co immunoprecipitation assays using ARP-1-selective antibodies revealed specific physical interactions between ARP-1 and the basal transcription factor TFIIB. We conclude that ARP-1 possesses intrinsic transcription activation potential which is modulated, at least in part, by the intracellular balance of other nuclear receptors that also bind to its cognate DNA binding site. PMID- 7784208 TI - Site-directed mutagenesis of the human DNA repair enzyme HAP1: identification of residues important for AP endonuclease and RNase H activity. AB - HAP1 protein, the major apurinic/apyrimidinic (AP) endonuclease in human cells, is a member of a homologous family of multifunctional DNA repair enzymes including the Escherichia coli exonuclease III and Drosophila Rrp1 proteins. The most extensively characterised member of this family, exonuclease III, exhibits both DNA- and RNA-specific nuclease activities. Here, we show that the RNase H activity characteristic of exonuclease III has been conserved in the human homologue, although the products resulting from RNA cleavage are dissimilar. To identify residues important for enzymatic activity, five mutant HAP1 proteins containing single amino acid substitutions were purified and analysed in vitro. The substitutions were made at sites of conserved amino acids and targeted either acidic or histidine residues because of their known participation in the active sites of hydrolytic nucleases. One of the mutant proteins (replacement of Asp-219 by alanine) showed a markedly reduced enzymatic activity, consistent with a greatly diminished capacity to bind DNA and RNA. In contrast, replacement of Asp 90, Asp-308 or Glu-96 by alanine led to a reduction in enzymatic activity without significantly compromising nucleic acid binding. Replacement of His-255 by alanine led to only a very small reduction in enzymatic activity. Our data are consistent with the presence of a single catalytic active site for the DNA- and RNA-specific nuclease activities of the HAP1 protein. PMID- 7784209 TI - Interaction of Xenopus TFIIIC with a 5S RNA gene. AB - Using fractionated Xenopus transcription factors we have identified and characterized a unique protein-DNA complex formed between TFIIIA, TFIIIC and a 5S RNA gene. The formation of this complex was blocked by specific competitor DNAs and by the inactivation of TFIIIC using two different methods. In addition, TFIIIC activity was retained when the complexes were affinity purified using a reversibly immobilized DNA template. The TFIII(A+C)-5S RNA gene complex has a distinct electrophoretic mobility on band-shift gels and a unique DNase I footprint. The characteristic feature of the DNase I footprint is a TFIIIC dependent extension of the TFIIIA footprint an additional 25 bp toward the 5' end of the gene. This indicates a direct interaction between Xenopus TFIIIC and the template DNA. PMID- 7784210 TI - Versatile vectors to study recoding: conservation of rules between yeast and mammalian cells. AB - In many viruses and transposons, expression of some genes requires alternative reading of the genetic code, also called recoding. Such events depend on specific mRNA sequences and can lead to read through of an in-frame stop codon or to +1 or -1 frameshifting. Here, we addressed the issue of conservation of recoding rules between the yeast Saccharomyces cerevisiae and mammalian cells by establishing a versatile vector that can be used to study recoding in both species. We first assessed this vector by analysing the site of +1 frameshift of the Ty1 transposon. Two sequences from higher organisms were then tested in both yeast and mammalian cells: the gag-pol junction of human immunodeficiency virus type 1 (HIV-1) (a site of -1 frameshift), and the stop codon region of the replicase cistron from the tobacco mosaic virus (a site of UAG read through). We show that both sequences direct a high level of recoding in yeast. Furthermore, different mutations of the target sequences have similar effects on recoding in yeast and in mouse cells. Most notably, a strong decrease of frameshifting was observed in the absence of the HIV-1 stem-loop stimulatory signal. Taken together, these data suggest that mechanisms of some recoding events are conserved between lower and higher eukaryotes, thus allowing the use of S. cerevisiae as a model system to study recoding on target sequences from higher organisms. PMID- 7784212 TI - Increased stability of nucleic acids containing 7-deaza-guanosine and 7-deaza adenosine may enable rapid DNA sequencing by matrix-assisted laser desorption mass spectrometry. AB - The use of matrix-assisted laser desorption mass spectrometry (MALDI-MS) has been suggested as an ultrafast readout of Sanger DNA sequencing ladders in a manner analogous to that used with sequencing gels. Currently, a serious limitation of MALDI-MS for the analysis of DNA results from the tendency for oligonucleotides to undergo facile fragmentation in the gas phase. The present study was undertaken to gain an understanding of the influence of various chemical structural features of purine bases on the stability of oligodeoxynucleotide ions produced by MALDI. The study focused on the stability of model compounds of the type d(TTTTTTTTTTXTTTTTTTTT TTTT), where T designates deoxythymidine and X a purine-containing 2'-deoxynucleotide. A variety of different purine derivatives were chosen as the base in the nucleotide X. The mass spectra of the model compounds containing 7-deaza analogues of guanine and adenine reveal a significantly increased stability compared to the 7-aza analogues under the conditions of MALDI-MS. The previously reported incorporation of the 7-deaza-2' deoxy-adenosine triphosphate and the 7-deaza-2'-deoxy-guanosine triphosphate into DNA by polymerases suggests their use in a Sanger dideoxy sequencing experiment. The dideoxy termination products with the 7-deaza-purines instead of the 7-aza purines might be sufficiently stable to allow separation and detection of the sequencing ladder by MALDI-MS. Thus, an ultrafast (seconds) read-out of DNA sequence may become feasible. PMID- 7784211 TI - Tandem repeats of the 5' non-transcribed spacer of Tetrahymena rDNA function as high copy number autonomous replicons in the macronucleus but do not prevent rRNA gene dosage regulation. AB - The rRNA genes in the somatic macronucleus of Tetrahymena thermophila are normally on 21 kb linear palindromic molecules (rDNA). We examined the effect on rRNA gene dosage of transforming T.thermophila macronuclei with plasmid constructs containing a pair of tandemly repeated rDNA replication origin regions unlinked to the rRNA gene. A significant proportion of the plasmid sequences were maintained as high copy circular molecules, eventually consisting solely of tandem arrays of origin regions. As reported previously for cells transformed by a construct in which the same tandem rDNA origins were linked to the rRNA gene [Yu, G.-L. and Blackburn, E. H. (1990) Mol. Cell. Biol., 10, 2070-2080], origin sequences recombined to form linear molecules bearing several tandem repeats of the origin region, as well as rRNA genes. The total number of rDNA origin sequences eventually exceeded rRNA gene copies by approximately 20- to 40-fold and the number of circular replicons carrying only rDNA origin sequences exceeded rRNA gene copies by 2- to 3-fold. However, the rRNA gene dosage was unchanged. Hence, simply monitoring the total number of rDNA origin regions is not sufficient to regulate rRNA gene copy number. PMID- 7784213 TI - The binding modes of a rationally designed photoactivated DNA nuclease determined by NMR. AB - The complex between the rationally designed synthetic DNA cleaving agent netropsin-diazene and the double-stranded DNA oligomer 5'-CGCAAAGGC-3'.5' GCCTTTTGCG-3' was characterized by two-dimensional NMR spectroscopy in solution. Photolysis of netropsin-diazene bound to DNA generates a trimethylenemethane diradical intermediate that induces single-strand breaks in the DNA. The pi-diyl trimethylenemethane based compounds are a new class of DNA nucleases. We tested the following design criteria: (i) binding of the diazene and subsequent reactive diyl to the DNA, (ii) sequence selectivity in the ligand binding and (iii) prevention of diyl dimerization. Sixteen NOE derived ligand-DNA distance restraints were used to obtain the energy minimized model of the complex. The ligand is bound to the minor groove of the oligomer with the diazene at the 5' end of the A-tract in the predominant conformation of the complex. This form of the complex exchanges with a minor conformation in which the ligand is in the opposite orientation. The DNA maintains a B-form structure. Netropsin-diazene has fulfilled all of the design criteria, binding to the DNA duplex studied in the minor groove of the central AAAA tract in a 1:1 mode, preventing diyl dimerization and other side reactions from occurring. PMID- 7784214 TI - Methylation of slipped duplexes, snapbacks and cruciforms by human DNA(cytosine 5)methyltransferase. AB - When human DNA(cytosine-5)methyltransferase was used to methylate a series of snapback oligodeoxy-nucleotides of differing stem lengths, each containing a centrally located CG dinucleotide recognition site, the enzyme required a minimum of 22 base pairs in the stem for maximum activity. Extrahelical cytosines in slipped duplexes that were 30 base pairs in length acted as effective methyl acceptors and were more rapidly methylated than cytosines that were Watson-Crick paired. Duplexes containing hairpins of CCG repeats in cruciform structures in which the enzyme recognition sequence was disrupted by a C.C mispair were also more rapidly methylated than control Watson-Crick-paired duplexes. Since enzymes have higher affinities for their transition states than for their substrates, the results with extrahelical and mispaired cytosines suggest that these structures can be viewed as analogs of the transition state intermediates produced during catalysis by methyltransferases. PMID- 7784215 TI - The DNA binding domain of the vaccinia virus early transcription factor small subunit is an extended helicase-like motif. AB - The vaccinia virus early transcription factor (VETF) is an ATP-dependent activator of the early class of viral genes. VETF is a heterodimeric protein that binds an initiator-like element surrounding the start site of transcription. Previous studies indicated that the small subunit of VETF contacts the promoter DNA. We have taken a mutational approach to determine sequences in the VETF small subunit that are important for DNA binding. Two types of sequences were targeted for mutation: ones resembling motifs that are conserved in the nucleic acid helicase family and positively charged residues in predicted alpha-helices. Mutations affecting transcription activation were clustered in two regions. One mutation that impaired DNA binding is located near the N-terminus within the putative ATP-binding pocket that comprises helicase domain I. DNA binding was also severely reduced by mutations in a sequence resembling helicase domain VI and two putative alpha-helices that flank this domain in the C-terminal third of the polypeptide. These results indicate that the DNA binding domain in the small subunit of VETF is not isolated within a separable domain as is the case with most transcription factors, but rather, spans most of the length of the 637 residue polypeptide. A model for VETF structure is suggested in which the active site for ATP hydrolysis is integrated within an extended DNA-binding domain such that the structure and function of each domain influences that of the other. PMID- 7784216 TI - Specific inhibition of DNA polymerase beta by its 14 kDa domain: role of single- and double-stranded DNA binding and 5'-phosphate recognition. AB - DNA polymerase beta (beta-polymerase) has been implicated in short-patch DNA synthesis in the DNA repair pathway known as base excision repair. The native 39 kDa enzyme is organized into four structurally and functionally distinct domains. In an effort to examine this enzyme as a potential therapeutic target, we analyzed the effect of various beta-polymerase domains on the activity of the enzyme in vitro. We show that the 14 kDa N-terminal segment of beta-polymerase, which binds to both single- and double-stranded DNA, but lacks DNA polymerase activity, inhibits beta-polymerase activity in vitro. Most importantly, the 8, 27 and 31 kDa domains of beta-polymerase do not inhibit beta-polymerase activity, demonstrating that the inhibition by the 14 kDa domain is specific. The inhibition of beta-polymerase activity in vitro is abolished by increasing the concentrations of both of the substrates (template-primer and deoxynucleoside triphosphate). In contrast, an in vitro base excision repair assay is inhibited in a domain specific manner by the 14 kDa domain even in the presence of saturating substrates. The inhibition of beta-polymerase activity by the 14 kDa domain appears specific to beta-polymerase as this domain does not inhibit either mammalian DNA polymerase alpha or Escherichia coli polymerase I (Klenow fragment). These data suggest that the 14 kDa domain could be used as a potential inhibitor of intracellular beta-polymerase and that it may provide a means for sensitizing cells to therapeutically relevant DNA damaging agents. PMID- 7784218 TI - 8-Methoxypsoralen photoinduced plasmid-chromosome recombination in Saccharomyces cerevisiae using a centromeric vector. AB - The characterization of a new system to study the induction of plasmid-chromosome recombination is described. Single-stranded and double-stranded centromeric vectors bearing 8-methoxypsoralen photoinduced lesions were used to transform a wild-type yeast strain bearing the leu2-3,112 marker. Using the SSCP methodology and DNA sequencing, it was demonstrated that repair of the lesions in plasmid DNA was mainly due to conversion of the chromosomal allele to the plasmid DNA. PMID- 7784217 TI - The HMG-1 box protein family: classification and functional relationships. AB - The abundant and highly-conserved nucleoproteins comprising the high mobility group-1/2 (HMG-1/2) family contains two homologous basic domains of about 75 amino acids. These basic domains, termed HMG-1 boxes, are highly structured and facilitate HMG-DNA interactions. Many proteins that regulate various cellular functions involving DNA binding and whose target DNA sequences share common structural characteristics have been identified as having an HMG-1 box; these proteins include the RNA polymerase I transcription factor UBF, the mammalian testis-determining factor SRY and the mitochondrial transcription factors ABF2 and mtTF1, among others. The sequences of 121 HMG-1 boxes have been compiled and aligned in accordance with thermodynamic results from homology model building (threading) experiments, basing the alignment on structure rather than by using traditional sequence homology methods. The classification of a representative subset of these proteins was then determined using standard least-squares distance methods. The proteins segregate into two groups, the first consisting of HMG-1/2 proteins and the second consisting of proteins containing the HMG-1 box but which are not canonical HMG proteins. The proteins in the second group further segregate based on their function, their ability to bind specific sequences of DNA, or their ability to recognize discrete non-B-DNA structures. The HMG-1 box provides an excellent example of how a specific protein motif, with slight alteration, can be used to recognize DNA in a variety of functional contexts. PMID- 7784219 TI - Enzymic removal of 5-methylcytosine from poly(dG-5-methyl-dC) by HeLa cell nuclear extracts is not by a DNA glycosylase. AB - A recent report in this journal [Vairapandi, M. and Duker, N.J. (1993) Nucleic Acids Res. 21, 5323-5327) presented evidence of an activity in HeLa cell nuclear extracts that released radiolabeled material from a poly(dG.dC) polymer that had been methylated and simultaneously labeled on cytosine residues by incubation with a CpG-specific DNA methylase and [methyl-3H]S-adenosylmethionine. Based on chromatographic evidence that the released products were thymine and 5 methylcytosine and on f1p4olabeling data suggesting a concomitant increase in abasic sites, the authors concluded that the releasing activity was a 5 methylcytosine-specific glycosylase and that the solubilized 5-methylcytosine was converted to thymine by a nuclear deaminase. We have confirmed that HeLa nuclear extracts promote release of ethanol-soluble radioactivity from a methyl-labeled poly(dG-5-methyl-dC)polymer, but the products released were neither 5 methylcytosine nor thymine. Furthermore, free 5-methylcytosine was not deaminated by incubation with the nuclear extract. The labeled compound released initially from the polymer appeared to be 5-methyl-deoxycytidine monophosphate, which was converted to 5-methyl-deoxycytidine, thymidine monophosphate, and/or thymidine by further incubation with the nuclear extract. The activity responsible for the release, therefore, was a nuclease. Release of 32P-labeled nucleotides from a 32P labeled poly(dG-dC) polymer suggested, furthermore, that the activity was not specific for methylated DNA. PMID- 7784220 TI - The G-rich auxiliary downstream element has distinct sequence and position requirements and mediates efficient 3' end pre-mRNA processing through a trans acting factor. AB - A downstream G-rich sequence (GRS), GGGGGAGGUGUGGG, has been previously shown to influence the efficiency of 3' end processing of the SV40 late polyadenylation signal. We have now defined several important parameters for GRS-mediated polyadenylation. The ability of the GRS to influence 3' end processing efficiency was sensitive to individual and multiple point mutations within the element, as well as the position of the element in the downstream region. Competition analysis indicated that the GRS functioned through a titratable trans-acting factor. The GRS-specific DSEF-1 protein was found to be bound to the same population of RNAs as the 64 kDa protein of the general polyadenylation factor CstF, indicating that DSEF-1 is associated with RNA substrates undergoing 3' end processing. Furthermore, an association was obtained between the relative strength of DSEF-1 protein binding to GRS variants and the relative ability of the GRS variants to mediate efficient cleavage in vitro. Finally, mutations in the GRS affected the efficiency of cross-linking of the 64 kDa protein of CstF. These data define a novel class of auxiliary downstream element and suggest an important role for DSEF-1 in 3' end processing. PMID- 7784222 TI - Single-step direct PCR amplification from solid tissues. PMID- 7784223 TI - Growth of E. coli at low temperature dramatically increases the transformation frequency by electroporation. PMID- 7784224 TI - Rapid and high efficiency site-directed mutagenesis by improvement of the homologous recombination technique. PMID- 7784221 TI - Identification of ribosome binding sites in Escherichia coli using neural network models. AB - This study investigated the use of neural networks in the identification of Escherichia coli ribosome binding sites. The recognition of these sites based on primary sequence data is difficult due to the multiple determinants that define them. Additionally, secondary structure plays a significant role in the determination of the site and this information is difficult to include in the models. Efforts to solve this problem have so far yielded poor results. A new compilation of E. coli ribosome binding sites was generated for this study. Feedforward backpropagation networks were applied to their identification. Perceptrons were also applied, since they have been the previous best method since 1982. Evaluation of performance for all the neural networks and perceptrons was determined by ROC analysis. The neural network provided significant improvement in the recognition of these sites when compared with the previous best method, finding less than half the number of false positives when both models were adjusted to find an equal number of actual sites. The best neural network used an input window of 101 nucleotides and a single hidden layer of 9 units. Both the neural network and the perceptron trained on the new compilation performed better than the original perceptron published by Stormo et al. in 1982. PMID- 7784226 TI - Genetics in cancer prediction, screening, and counseling: Part I, Genetics in cancer prediction and screening. AB - PURPOSE/OBJECTIVES: To review molecular biology and gene technology as they relate to cancer prediction and screening. DATA SOURCES: Published professional articles, texts, and proceedings; computerized data bases. DATA SYNTHESIS: Basic principles of inheritance and mutations; a discussion of proto-oncogenes, oncogenes, and anti-oncogenes; a summary of gene-mapping techniques; and a review of genes linked to familial, breast, ovarian, and colorectal cancers. CONCLUSIONS: Most human cancers are influenced genetically but are not inherited. Discoveries about cancer genes play a major role in identifying individuals and families who are likely to develop cancer. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to heighten their awareness of this science and its ramifications, which ultimately will affect recommendations for early detection and screening. PMID- 7784227 TI - Genetics in cancer prediction, screening, and counseling: Part II, The nurse's role in genetic counseling. AB - PURPOSE/OBJECTIVES: To describe an expanded role for oncology nurses in genetic counseling for cancer. DATA SOURCES: Published professional articles, computerized data bases, lay publications. DATA SYNTHESIS: A description of the availability of genetic counseling, of motivation for undergoing genetic counseling, and of the basic components of genetic counseling for cancer. CONCLUSIONS: The need for genetic counseling will increase as more families with inherited cancer are identified, more cancer genes are isolated, and genetic analysis becomes more available. IMPLICATIONS FOR NURSING PRACTICE: Advances in genetic technology provide nurses with the opportunity for an expanded role in genetic counseling for cancer. Oncology nurses also can act as case finders of families with inherited cancers and conduct research in this area. PMID- 7784228 TI - Gene therapy: current strategies and future applications. AB - PURPOSE/OBJECTIVES: To provide a brief introduction to gene therapy, including gene transfer methods and safety issues, as well as the role of nursing in gene therapy. To identify current applications of gene therapy in oncology. DATA SOURCES: Published articles, book chapters, and the author's experience with the care of patients receiving gene therapy. DATA SYNTHESIS: Gene therapy is used to add a new function to cells or to label cells for future identification. Presently, gene transfer is accomplished primarily through safety-modified retroviral vectors. A variety of innovative gene therapy approaches currently are being investigated in clinical trials, but no outcomes have been reported. CONCLUSIONS: Gene therapy is a new, rapidly-evolving investigational modality with promising applications in the treatment of patients with brain, skin, kidney, and other cancers and patients who are undergoing bone marrow transplantation. NURSING IMPLICATIONS: Gene therapy is an investigational modality in phase I clinical trials that requires thorough patient care planning and patient monitoring for unexpected side effects. There is an increasing need for nurses to understand gene therapy so that they can educate patients and families. PMID- 7784229 TI - Genetics in cancer care: confronting a Pandora's Box of dilemmas. AB - PURPOSE/OBJECTIVES: To provide an overview of sociopolitical, bioethical, and psychological issues emerging from the application of genetic technologies in cancer care in the United States and to provoke oncology nurses to consider the impact that advances in genetics may have on their practice. DATA SOURCES: Published professional articles, tests, and proceedings as well as government and lay publications. DATA SYNTHESIS: This article reviews underlying sociopolitical issues and forecasts bioethical dilemmas and psychological responses likely to emerge from expanding genetic screening and treatment options in oncology. The sociopolitical issues revolve around individual rights, the role of government, and the influence of religious dogma and public perception. The bioethical dilemmas fall within a framework of five scenarios, and a range of psychological responses are described. CONCLUSIONS: Significant changes will occur in cancer care as a result of advances in genetic technology. These changes will be accompanied by a new set of dilemmas in clinical practice and by as yet undescribed psychological responses. In addition to building a knowledge base relevant to these new technologies, oncology nurses must anticipate the new dilemmas and be prepared to manage the emotional responses of their patients. NURSING IMPLICATIONS: Nurse are in a strategic position to make significant contributions to the genetics data base by designing and conducting research to describe the ethical dilemmas and patient/family responses engendered as genetic science is integrated into cancer care. PMID- 7784230 TI - The human genome exposed: a glimpse of promise, predicament, and impact on practice. AB - PURPOSE/OBJECTIVES: To review basic gene biology, discuss current genetic advances, and project the potential impact of these advances on oncology nursing practice. DATA SOURCES: Published professional articles, tests, proceedings, governmental and lay publications. DATA SYNTHESIS: The Human Genome Project seeks to better describe the human complement of genes, which may hold the key to further defining the mechanism of carcinogenesis. The identification of genetic defects responsible for cancer will facilitate development of both preventive and therapeutic antitumor strategies. CONCLUSIONS: The data base emerging from genetic research will result in both promise and predicaments. The promise relates to the discovery of genetic abnormalities that can be used to predict risk for cancer or serve as targets for therapeutic intervention. The predicaments involve the psychosocial, ethical, and legal implications of revealing an individual's genetic profile without knowing the ultimate ramifications of that information. IMPLICATIONS FOR NURSING PRACTICE: Nurses will be at the forefront of these advances as they describe the effects of genetic advances on the public and on individuals and create innovative strategies to manage negative effects. To take advantage of opportunities presented by the genetic revolution, nurses must develop a knowledge base about gene biology and its relationship to cancer. PMID- 7784225 TI - Splinkerettes--improved vectorettes for greater efficiency in PCR walking. PMID- 7784231 TI - Australian NHMRC Twin Registry: a resource for pediatric research. PMID- 7784232 TI - Effect of technical development on the apparent incidence of congenital heart disease. PMID- 7784233 TI - Histopathology of the ductus arteriosus after PGE1 treatment. PMID- 7784234 TI - Hemolysis associated with umbrella occlusion of the arterial duct. PMID- 7784237 TI - Chest pain in children referred to a cardiology clinic. AB - One hundred consecutive patients (54 girls, 46 boys) referred to a pediatric cardiology department with the primary complaint of chest pain were evaluated. The age distribution was 2.5-16.0 years (mean 11.3 years for girls and 9.9 years for boys). The history showed 17% of patients with chest pain, 22% with heart disease, and 19% with recent death in the family. The time course of the pain was longer than 1 week in 92 patients. Localization was on the left precordium in 60 patients, and there was no radiation from the original site in 66 cases. Ninety two percent of cases were idiopathic in origin. Of the 74 patients who had a psychiatric interview, 55 (74%) had psychiatric symptoms and 5 required psychiatric care. Anxiety, conversion disorder, and depression were the main psychiatric symptoms. PMID- 7784236 TI - Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis. AB - Among 68 children with severe dilated cardiomyopathy, 43 (aged 10 months to 15 years) presented with active myocarditis, diagnosed by endomyocardial biopsy. They were divided into four treatment groups: I, controls: 9 patients submitted to conventional treatment (digitalis, diuretics, and vasodilators) for 8.1 +/- 0.7 (SD) months; II, prednisone: 12 patients received conventional therapy plus prednisone; III, azathioprine: 16 patients submitted to conventional therapy plus prednisone and azathioprine; IV, cyclosporine: 13 patients treated with conventional therapy plus prednisone and cyclosporine. Immunosuppressive therapy was maintained for a mean of 8.4 +/- 1.2 months. They were submitted to noninvasive (electrocardiogram, chest radiograph, Doppler echocardiogram, and radioisotopic scintigraphy) and invasive (hemodynamic) studies. In the control group only 2 of 9 patients showed clinical and hemodynamic improvement and 1 of 4, histologic regression of the myocarditis. Among patients submitted to conventional therapy plus prednisone, 3 of 12 presented clinical and hemodynamic improvement; 2 of 5 also showed histologic regression of inflammatory process. By contrast, patients treated with azathioprine or cyclosporine associated with prednisone had significantly better results: 13 of 16 and 10 of 13 patients, respectively, had clinical and hemodynamic improvement; all 6 patients in the azathioprine group and all 4 patients in the cyclosporine group had histologic regression of the myocarditis. Two patients in the prednisone group, one in the azathioprine group, and one in the cyclosporine group died during treatment, in cardiogenic shock. In our experience immunosuppressive therapy with azathioprine or cyclosporine associated with prednisone improves the prognosis of children with active myocarditis and severe ventricular dysfunction. PMID- 7784238 TI - Congenital valvar aortic stenosis and abnormal origin of the right coronary artery: rare combination with important clinical implications. AB - Congenital valvar aortic stenosis in association with an abnormal coronary artery origin and distribution has not been previously reported. The right coronary artery arose in the left ventricular (LV) outflow tract and supplied much of the LV myocardium. Aortic valvotomy with standard antegrade cardioplegia resulted in infarction of the left ventricle. Aggressive attempts to ascertain the origin of the coronary arteries in right dominant coronary systems must be performed before any intervention in this group of patients. PMID- 7784235 TI - Relation between age at surgery and regression of right ventricular hypertrophy in tetralogy of Fallot. AB - Pre- and postoperative echocardiographic right ventricular wall thickness (RVW), transverse dimension (RVD), and their ratio (W/D) were measured from subcostal views in 29 patients with Tetralogy of Fallot (TOF) in order to assess whether primary reparative surgery without prior palliative shunts in early infancy results in significantly faster regression of RV hypertrophy than repair later in life. Fourteen patients who were repaired before 6 months of age were compared with 15 patients who were repaired after 6 months of age. In the group of patients who were repaired before 6 months of age both RVW and W/D ratio decreased significantly whereas RVD did not change from pre- to postoperative status. The group of patients who were repaired after 6 months of age showed no significant changes in RVW, RVD, or W/D ratio. These findings suggest that early primary reparative surgery of TOF may have a positive effect on faster regression of RVH during the first postoperative year which may reduce the detrimental effect of longstanding hypertrophy on myocardial function and the potential for arrhythmia. PMID- 7784239 TI - Reversible cardiomyopathy due to carnitine deficiency from renal tubular wasting. AB - The clinical course of a 4-month-old male infant with a dilated cardiomyopathy secondary to renal tubular losses of carnitine is outlined. He was admitted to the hospital with severe congestive heart failure. An echocardiogram demonstrated normal anatomy. The left ventricular shortening fraction measured 10%. A comprehensive cardiomyopathy evaluation was initiated. The total plasma carnitine level was only 25 mumol/ml, but the urine carnitine measured 434 nm/mg of creatinine. He was begun on oral L-carnitine and weaned from mechanical ventilation and inotropic support 10 days later. Two years later he remains asymptomatic with normal left ventricular function. PMID- 7784240 TI - Effective use of magnesium for acquired torsade de pointes in a 4-month-old infant. AB - We report a 4-month-old infant with torsade de pointes secondary to procainamide treatment. The infant presented with atrial flutter and converted to normal sinus rhythm with intravenous procainamide. Oral procainamide therapy was initiated as the infusion was tapered, and the patient subsequently developed incessant torsade de pointes. Once the proarrhythmia was recognized, procainamide was withheld, and intravenous magnesium was administered. The torsade de pointes resolved after one bolus of magnesium sulfate. An infusion regimen of magnesium was given until the procainamide and N-acetylprocainamide concentrations became undetectable. Intravenous magnesium should be administered to newborns with acquired torsade de pointes; dosing guidelines for its use are suggested. PMID- 7784242 TI - Intussusception of the catheter sheath: a nonemergency. AB - Percutaneous balloon dilatation angioplasty is a common therapeutic modality in patients with congenital heart disease. We report three cases of the catheter sheath telescoping into the hub of the sheath after removal of the balloon catheter. Although initially it appeared as though the sheath was torn, in actuality it was intact. We report this problem so others can avoid needless searching and concern for the "missing" catheter tip. PMID- 7784241 TI - Ventricular fibrillation in two infants treated with amiodarone hydrochloride. AB - Antiarrhythmic agents may induce ventricular arrhythmias. Whereas amiodarone is a reported cause of ventricular fibrillation in children, there are no reported cases in infants. We observed two patients with atrial flutter and congestive heart failure who were treated with amiodarone. Both had anatomic heart defects and had failed conventional therapy. Ventricular fibrillation occurred 3 and 12 days after the initial dose. Q-T interval, electrolytes, digoxin level, and amiodarone level (one patient) were normal. Amiodarone may provoke life threatening ventricular tachyarrhythmias during the convalescent period. Consideration should be given to monitoring in a hospital setting for at least 2 weeks following initiation of amiodarone therapy. PMID- 7784243 TI - Biphasic flow velocity pattern in the descending aorta in double aortic arch. AB - We report a case of double aortic arch in which the biphasic flow velocity pattern in the descending aorta changed to a monophasic flow velocity pattern after corrective surgery. The hypoplasia of left aortic arch might prolong the acceleration time of the flow velocity in the left aortic arch. PMID- 7784244 TI - Pulmonary atresia and ventricular septal defect with coronary artery to pulmonary artery fistula: case report and review of the literature. AB - The pulmonary blood supply in patients with pulmonary atresia and ventricular septal defect is highly variable. Several cases have been reported in the literature in which a coronary artery to pulmonary artery fistula, alone or in combination with additional vessels, supplies the pulmonary circulation. We report a case of successful repair during early infancy, with unique hemodynamic, clinical, and anatomic features. The literature is reviewed. PMID- 7784245 TI - Unusual combination of congenital heart defects in an infant with Noonan syndrome. AB - Congenital heart disease occurs in 35-50% of patients diagnosed with Noonan syndrome. We present an infant with an unusual combination of congenital heart defects not previously reported, including partial atrioventricular septal defect, polyvalvular dysplasia, and progressive hypertrophic cardiomyopathy. We discuss the possible interaction between these lesions that may have led to the patient's rapid demise. PMID- 7784246 TI - Effect of acute and chronic treatment with desglycinamide-[Arg8]vasopressin in young male and female volunteers. AB - A single dose of DGAVP (2 mg) and a chronic treatment of 2 weeks (1 mg/day) were given to male and female volunteers by the intranasal route. Memory, mood, vigilance, and attention were tested starting 60 min after treatment. Initial storage of abstract words was improved in the males but not in the females after chronic treatment with DGAVP. This effect persisted after discontinuation of treatment. Initial storage and learning of concrete words were not affected by treatment with DGAVP. Chronic, but not acute, treatment with DGAVP reduced the reaction time for scanning of digits in a memory comparison task (Sternberg paradigm) in both sexes. No treatment effects were found for visual memory, vigilance, attention, mood, or blood pressure. The present study indicates a sexual dimorphism in the effect of DGAVP on certain memory processes. PMID- 7784247 TI - Third trimester POMC disregulation predicts use of anesthesia at vaginal delivery. AB - In a prospective study, third trimester plasma levels of BE and ACTH were determined in 58 women who delivered vaginally. Peptide regulation was compared between subjects who used conduction anesthesia at delivery and subjects who did not. Third trimester levels of maternal BE and ACTH were significantly related; however, the relationship was significant only in subjects who did not receive conduction anesthesia (n = 24) at delivery. The normal co-release pattern between BE and ACTH in subjects receiving conduction anesthesia (n = 34) during birth was uncoupled. The use of conduction analgesia during vaginal delivery was significantly related to a disregulation index created to quantify the BE-ACTH release pattern. Uncoupled ACTH and BE patterns may result from modified control of pro-opiomelanocortin (POMC) expression during pregnancy or unique proteolytic processing of POMC, and may alter pain tolerance during delivery. PMID- 7784248 TI - Opioid peptide receptor studies. 1. Identification of a novel delta-opioid receptor binding site in rat brain membranes. AB - Our laboratory was among the first to propose the existence of delta receptor subtypes: a delta site thought to be associated with a mu-delta-opioid receptor complex termed the delta cx binding site and delta site not associated with the mu-delta-opioid receptor complex, termed the delta ncx site. In previous studies, we assayed the delta cx site with [3H][D-Ala2,D-Leu5]enkephalin using rat brain membranes depleted of delta ncx sites by pretreatment with the site-directed acylating agent, (+)-trans-SUPERFIT. In the present study, we investigated, using (+)-trans-SUPERFIT-pretreated membranes, the possibility of heterogeneity of the delta cx binding site. Two sites were resolved: the delta cx-1 site at which mu ligands are potent noncompetitive inhibitors and delta ligands are weak competitive inhibitors, and the delta cx-2 site where delta ligands are potent and mu ligands are weak, mixed competitive-noncompetitive inhibitors. Although the delta cx-2 site has a delta-like ligand-selectivity profile, several experiments distinguished it from the delta ncx site. Two lines of evidence suggest that the delta ncx site corresponds to the cloned delta receptor. One, the delta receptor was cloned from the NG108-15 cell line, and this receptor, like the delta ncx binding site, irreversibly binds SUPERFIT and (+)-trans SUPERFIT. Secondly, administration of delta-antisense DNA selectively decreases delta ncx binding. Viewed collectively, the major finding of this study is the discovery of a novel SUPERFIT-insensitive and delta-antisense-insensitive delta cx-2 binding site. PMID- 7784250 TI - Synthesis and biological activity of N-terminal-truncated derivatives of human epidermal growth factor (h-EGF). AB - To investigate the contribution of the N-terminal sequence of h-EGF to its biological activity and the formation of three intramolecular disulfide bonds by oxidative refolding via air oxidation, five derivatives of h-EGF with a single N terminal amino acid deletion were synthesized by solid-phase synthesis. The homogeneity of the synthetic peptides was confirmed by analytical reversed-phase HPLC, amino acid analysis, and FAB-MS. The pairing of the three disulfide bridges in synthetic peptides was determined by thermolytic digestion. All N-truncated derivatives of h-FGF formed the correct intramolecular three disulfide linkages during oxidative refolding and had equipotent activity in both EGF receptor binding on A-431 epidermoid carcinoma cells and mitogenesis on NIH-3T3 fibroblast cells, compared with authentic h-EGF. The results suggested that the five residues from N-terminal sequence of h-EGF have no effect on the formation of the correct disulfide linkages in h-EGF and do not exert a significant influence on its biological activity. PMID- 7784249 TI - Structure-activity relationships of the crustacean myotropic neuropeptide orcokinin. AB - Orcokinin (OK, NFDEIDRSGFGFN) was recently identified from the crayfish, Orconectes limosus, as a potent hindgut-stimulating factor (14). To assess the importance of structural features of the peptide involved in effective ligand receptor interactions, synthetic analogues of orcokinin were tested in the hindgut bioassay. Tests with N- and C-terminal-truncated analogues and the C terminal-amidated analogue (OK-NH2) demonstrate that changes at the C-terminus interfere less with biological activity than changes at the N-terminus. Removal of more than one amino acid at the N-terminus resulted in a complete loss of activity, whereas the C-terminal deletion of three amino acids still produced an analogue with full intrinsic activity but with a drastic shift in threshold concentration of activity from 1 x 10(-10) to 1 x 10(-7) M. Deletion of four amino acids at the C-terminus resulted in a completely inactive analogue. The C terminal hydroxyl group does not seem to be important because amidation (OK-NH2) resulted in almost no loss of activity. Replacing Arg7 with Ala produced an analogue almost equipotent to orcokinin. Replacement of Phe2 by Tyr resulted in considerable loss of activity. An important role of Phe2 is further suggested by the steep drop of activity after removal of this residue in the N-terminal deleted analogues. PMID- 7784251 TI - Pheromonotropic activity of naturally occurring pyrokinin insect neuropeptides (FXPRLamide) in Helicoverpa zea. AB - Insect neuropeptides, having the common C-terminal sequence FXPRLamide X = V, T, S, or G), were tested for phyeromonotropic activity in the moth, Helicoverpa zea. Dose-response studies indicated that locustamyotropin-II or locustapyrokinin-II induced production of more pheromone than was stimulated by the pheromone biosynthesis activating neuropeptide of this moth. Other peptides showed various degrees of pheromonotropic activity. The data indicated that substitution of the variable amino acid in the C-terminal pentapeptide sequence resulted in significant differences in pheromonotropic activity. However, the overall structure of the peptide was also found to be of importance. PMID- 7784252 TI - [125I]SNF 8702: a selective radioligand for CCKB receptors. AB - The CCK-8 analogue, SNF 8702, was radioiodinated. [125I]SNF 8702 showed high affinity specific binding for both guinea pig and mouse brain tissues, whereas no specific binding was seen for guinea pig pancreatic tissue. The properties of the site labeled by [125I]SNF 8702 were characterized by binding inhibition studies for a series of CCKA and CCKB receptor ligands. The binding selectivity profile corresponded to that for the CCKB receptor. The labeled compound is stable for more than 6 weeks during storage at -20 degrees C. PMID- 7784253 TI - Glucagon-like peptide-1 binding to rat skeletal muscle. AB - We have found [125I]glucagon-like peptide-1(7-36)-amide-specific binding activity in rat skeletal muscle plasma membranes, with an estimated M(r) of 63,000 by cross-linking and SDS-PAGE. The specific binding was time and membrane protein concentration dependent, and displaceable by unlabeled GLP-1(7-36)-amide with an ID50 of 3 x 10(-9) M of the peptide; GLP-1(1-36)-amide also competed, whereas glucagon and insulin did not. GLP-1(7-36)-amide did not modify the basal adenylate cyclase activity in skeletal muscle plasma membranes. These data, together with our previous finding of a potent glycogenic effect of GLP-1(7-36) amide in rat soleus muscle, and also in isolated hepatocytes, which was not accompanied by a rise in the cell cyclic AMP content, lead use to believe that the insulin-like effects of this peptide on glucose metabolism in the muscle could be mediated by a type of receptor somehow different to that described for GLP-1 in pancreatic B cells, where GLP-1 action is mediated by the cyclic AMP adenylate cyclase system. PMID- 7784254 TI - Identification of a new chromogranin B fragment (314-365) in endocrine tumors. AB - A rabbit antiserum was raised against the fragment (350-365) of human chromogranin B corresponding to the C-terminal end of a putative proteolytic fragment generated by the cleavage of a dibasic doublet located in position 366 367 of the precursor. A radioimmunoassay was developed. Chromatographic analysis of 10 endocrine tumor extracts (one liver metastasis of a gastrinoma, one liver metastasis of a medullary carcinoma of the thyroid, one VIPoma, one insulinoma, one nonsecreting pancreatic endocrine tumor, one local recurrence of a gut carcinoid, two pituitary gonadotropinoma, and two non-secreting pituitary adenomas) revealed the presence of two forms of immunoreactive material. The most abundant form had an apparent molecular weight of 4500 and was purified to homogeneity by successive reverse-phase HPLC chromatographies and partially sequenced. The N-terminal sequence of the peptide, established by automated Edman degradation, was A-S-E-E-E-P-E-Y-G-E-E-I-K-G-Y-P-V-Q and corresponded to the 314 332 sequence of human chromogranin B. Taking into account the specificity of the antiserum used for peptide identification, we deduced that the purified peptide was chromogranin B(314-365) and represented a new form generated by limited proteolysis of chromogranin B. PMID- 7784255 TI - Triiodothyronine regulates somatostatin gene expression in cultured fetal rat cerebrocortical cells. AB - The effect of triiodothyronine (T3) on somatostatin (SS) mRNA levels in cultured fetal rat cerebrocortical cells was studied. Two different experimental approaches were sought. They differed in the length of time in which cells were deprived of thyroid hormones prior to the addition of exogenous T3. When the cells were not deprived of thyroid hormones, T3 caused a dose-related decrease in SS mRNA content at all doses tested. However, when the cells were deprived of T3 for 24 h, a biphasic effect was observed. These findings suggest that T3 regulates SS gene expression in fetal cultured cerebrocortical cells. PMID- 7784256 TI - Synthetic peptides demonstrate RGD-independent platelet glycoprotein IIb/IIIa recognition site in cell binding domain of human fibronectin. AB - Fibronectin binds to platelet membrane glycoprotein (GP) IIb/IIIa in both an Arg Gly-Asp (RGD)-dependent and -independent manner. The identification of an RGD independent binding domain(s) that interacts with GPIIb/IIIa may be the key to understand the mechanism of thrombus formation. A recombinant fibronectin fragment containing the residues from Ile1359 to Ser1436 (lacking the RGD sequence) had been shown to bind to GPIIb/IIIa in a divalent cation- and activation-dependent manner. To identify a minimal peptide ligand that participates in the recognition of GPIIb/IIIa, we synthesized peptides extending this region, which consist of 12 amino acid residues in length and overlapping by six amino acids. We obtained evidence that two 12-residue peptide sequences from this region (residues 1371-1382 and 1377-1388) inhibit fibronectin binding to GPIIb/IIIa by interacting directly with this receptor, with IC50s of 95 +/- 16 and 104 +/- 19 microM, respectively. These peptides inhibited the binding of fibrinogen to GPIIb/IIIa, as well as ADP-induced platelet aggregation. These results indicate that an RGD-independent GPIIb/IIIa binding site in the cell binding domain of fibronectin was localized within the residues His1377-Ile1382. PMID- 7784257 TI - Effects of testosterone on the behavioral response to arginine vasopressin microinjected into the central gray and septum. AB - Arginine vasopressin (AVP) plays an important role in the control of a gonadal hormone-dependent communicative behavior in the Syrian hamster (Mesocricetus auratus) called flank marking. Previous studies have shown that gonadal hormones alter the amount of flank marking stimulated by the microinjection of AVP into the medial preoptic area-anterior hypothalamus (MPOA-AH). The purpose of the present study was to determine if testicular hormones alter the amount of flank marking stimulated by the microinjection of AVP into two other sites involved in the control of flank marking, the lateral septum-bed nucleus of the stria terminalis (LS-BNST) and the central gray. The data of the present study indicate that testicular hormones may influence the amount of AVP-stimulated marking in the central gray and LS-BNST; however, these effects are subtle and appear to occur primarily at high concentrations of AVP. When taken together with previous studies, these data indicate that gonadal hormones have greater effects on AVP stimulated marking in the MPOA-AH than in the LS-BNST or central gray. PMID- 7784258 TI - Bombesin stimulates c-fos and c-jun mRNAs in small cell lung cancer cells. AB - The effects of bombesin/gastrin-releasing peptide (BN/GRP) on c-fos and c-jun gene expression were investigated using small cell lung cancer (SCLC) cells. BN (10 nM) increased c-fos mRNA fivefold using NCI-H345 or NCI-H510 cells. The increase was concentration dependent with 1 nM BN half-maximally increasing c-fos mRNA. Also, the increase in c-fos mRNA caused by BN was time dependent, being maximal after 1 h and returning to basal values after 4 h. GRP and GRP(14-27) but not GRP(1-16) increased c-fos mRNA. BW2258U89 (1 microM), a GRP receptor antagonist, had no effect on basal c-fos but inhibited the increase in c-fos mRNA caused by 10 nM BN. Also, BN transiently increased c-jun mRNA twofold and the increase caused by BN was blocked by BW2258U89. These data suggest that GRP receptors may regulate nuclear oncogene gene expression in SCLC cells. PMID- 7784259 TI - Effects of calcitonin gene-related peptide on intracellular calcium concentration in longitudinal muscle of guinea pig ileum. AB - The effect of rat calcitonin gene-related peptide (rCGRP) on intracellular free calcium concentration ([Ca2+]i) and its relationship with muscle relaxation were examined in plexus-free longitudinal muscle (LM) of the guinea pig ileum using a [Ca2+]i-tension simultaneous recording technique. Tissue was stimulated with either histamine (0.5 microM) or KCl (30 mM). rCGRP at a concentration of 263 nM (which displayed maximal relaxation of the LM) caused a small and brief but significant decrease in the [Ca2+]i in histamine-treated tissue. On the other hand, the same concentration of rCGRP relaxed the muscle without affecting the [Ca2+]i in KCl-treated tissue. rCGRP caused a dissociation between the changes in [Ca2+]i and tension. The effects of forskolin 0.5 microM) and nifedipine (10 nM) on both [Ca2+]i and tension were examined in comparison with rCGRP. Forskolin lowered the tension to greater extent than the [Ca2+]i whereas nifedipine (10 nM) diminished both the [Ca2+]i and tension in a parallel manner in histamine-treated tissues. These results suggest that rCGRP may not reduce [Ca2+]i as its primary mechanism of relaxation and it may change the calcium sensitivity of the contractile elements of the smooth muscle. PMID- 7784260 TI - Validation, role in perioperative assessment, and clinical applications of an immunoradiometric assay for human calcitonin. AB - We have evaluated a new immunoradiometric assay (IRMA) for calcitonin (CT) (Medgenix, Belgium). The detection limit of immunoreactive CT (IR-CT) was 2.8 pg/ml, and plasma levels of IR-CT of 134 healthy adults (dynamic range, 2.8-1000 pg/ml) were < 19 pg/ml (median 4.1 pg/ml). Both basal and pentagastrin-stimulated IR-CT levels were < 30 pg/ml and were well separated from the levels in patients with medullary thyroid carcinoma (MTC) (46-29,000 pg/ml, n = 38). In preoperative plasma samples in five patients with C-cell hyperplasia, CT IRMA confirmed the diagnosis, although in two patients RIA failed to detect a significant increase of IR-CT. By modifying the IRMA, we could identify residual tumor tissues perioperatively in patients undergoing thyroidectomy for MTC. RIA of gel permeation chromatography showed four IR-CT peaks, but IRMA had only three peaks, suggesting that IRMA is more specific. CT-IRMA is more specific, sensitive, robust, rapid, and reliable than RIA. In addition, neat plasma can be used directly in a single step in CT-IRMA. PMID- 7784261 TI - Homologous regulation of vasoactive intestinal peptide (VIP) receptors on rat peritoneal macrophages. AB - In the present study, we examined the effect of pretreatment with VIP and various peptides structurally related to VIP such us PHI, helodermin, and secretin on VIP receptor number and affinity, as well as VIP-stimulated cyclic AMP production in rat peritoneal macrophages. Short-term (5-30 min) exposures of rat peritoneal macrophages to 0.1 microM VIP induced a rapid reduction in specific binding. Pretreatment for 15 and 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, causing a decrease of 67% (SEM = 6) in specific binding. Pretreatment with 0.1 microM VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respectively. Only VIP concentrations at the nanomolar level and higher were shown to be effective. The potency of VIP and related peptides to desensitize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was also studied. It was shown that receptor-bound ligand is internalized during the downregulation process. However, the diminution in VIP binding to macrophages was not completely explained by internalization. PMID- 7784262 TI - Pharmacological evidence for the involvement of endogenous alpha-MSH-like peptides in peripheral nerve regeneration. AB - The possible involvement of alpha-MSH-like peptides in the regenerative response of peripheral nerves was investigated with a competitive antagonist of alpha-MSH, the synthetic hexapeptide [D-Trp7,Ala8,D-Phe10)alpha-MSH(6-11)-amide. Subcutaneous administration of the alpha-MSH antagonist during the first 10 days following sciatic nerve crush significantly decreased functional recovery as measured by the foot flick withdrawal test and the walking pattern analysis. Hypophysectomy delayed both the initial sprouting response and the outgrowth rate after major caudal nerve crush. When hypophysectomized rats were treated with the alpha-MSH antagonist, a further delay in initial sprouting was observed, whereas the outgrowth rate of nerve fibers was not affected. These results suggest that 1) endogenous alpha-MSH-like peptides stimulate nerve outgrowth following peripheral nerve injury and 2) alpha-MSH-like peptides derived from a source other than the pituitary may contribute to the physiological stimulus leading to sprouting. PMID- 7784263 TI - Properties of rat brain dipeptidyl aminopeptidases in the presence of detergents. AB - Rat brain dipeptidyl aminopeptidases I to IV were assayed in the soluble and membrane-bound fractions of rat brain, and the effects of the detergents Triton X 100 and sodium deoxycholate on their activities were studied. Dipeptidyl aminopeptidases I and II were significantly inhibited in the presence of sodium deoxycholate, but were not affected by the presence of Triton X-100. However, dipeptidyl aminopeptidase III was not influenced by either detergent, whereas the activity of dipeptidyl aminopeptidase IV was stimulated in the presence of Triton X-100, but remained unaffected by deoxycholate. These effects were partially or totally reversed after detergents were removed from the medium with adsorbent polymeric beads. Although detergents may have different effects on each DAP activity, the behavior of each enzyme activity in the presence of these substances was similar regardless of their subcellular location. These findings suggest that, as with other aminopeptidases, each of these proteins corresponds to the same molecular species in two different cell compartments. PMID- 7784264 TI - Processing of the L5-67 precursor peptide and characterization of LUQIN in the LUQ neurons of Aplysia californica. AB - Metabolic labeling of the dorsal Left Upper Quadrant (LUQ) cells of the abdominal ganglion of Aplysia californica and RP-HPLC separation of their peptide content allowed us to identify the L5-67 precursor and its processed peptides. Cleavage of the signal peptide occurred between amino acids 23 and 24 of the prepropeptide and generated a propeptide of 89 amino acids. Further processing by endopeptidases at the twin basic residues Lys12-Arg13 of the precursor generated a peptide of 76 amino acids, as well as an amidated decapeptide, LUQIN. The sequence of LUQIN was determined by amino acid sequencing and by its comigration with the synthetic peptide Ala-Pro-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-amide in three different RP-HPLC systems. The amidation of LUQIN was further demonstrated by its resistance to carboxypeptidase A digestion. PMID- 7784265 TI - Characterization of neurotensin-like immunoreactivity in human basal ganglia: increased neurotensin levels in substantia nigra in Parkinson's disease. AB - A method that combines high performance liquid chromatography with radioimmunoassay (HPLC/RIA) has been used to characterize neurotensin-like immunoreactivity (NT-IR) in the basal ganglia from control subjects and Parkinson's disease (PD) patients. In samples from the caudate nucleus and putamen, NT-IR eluted as two HPLC peaks. One was indistinguishable from the synthetic tridecapeptide, while the other peak corresponded to oxidized NT, as judged by its chromatographic behaviour and its reaction with the antiserum employed. There were marked discrepancies between the IR detected in crude extracts and that in HPLC purified samples. NT levels (HPLC/RIA) were unaltered in the caudate nucleus, putamen and both segments of the globus pallidus in the parkinsonian brain. In contrast, there was a two-fold increase in NT content in both zona compacta and zona reticulata of the substantia nigra in PD patients compared to controls. Degeneration of the nigrostriatal pathway and/or prolonged antiparkinsonian treatment in PD appears to alter neurotensin levels in an attempt to activate the dopaminergic nigrostriatal pathway. PMID- 7784266 TI - Neuropeptide FF-like immunoreactivity in human plasma. AB - In order to examine whether neuropeptide FF (NPFF), an octapeptide with pain modulating and blood pressure-raising properties in the rat, is present in circulating human blood, a radioimmunoassay (RIA) was established. Using this highly specific and sensitive RIA, the mean concentration of NPFF in human plasma was 2.9 pg/ml +/- 1.1 (n = 111). The concentration did not correlate with age or sex. Reversed-phase high pressure liquid chromatography (HPLC) followed by RIA using two different antisera for NPFF showed that plasma NPFF eluted in a position identical to that of synthetic NPFF. In view of published Kd values (0.06 mM) for NPFF receptor, the concentrations detected of NPFF in human plasma may be too low for systemic actions. Thus, plasma NPFF may represent leakage of the peptide from nervous tissue. PMID- 7784267 TI - Delta-opioid peptide receptors in muscles from obese diabetic and normal mice. AB - Autoradiography was used to study the opioid receptors in soleus and extensor digitorum longus (EDL) muscles from normal mice and mice with type II diabetes. Binding sites for [125I]beta-endorphin were present on the surface membranes in muscles from normal mice. The density of receptors was higher in muscles from obese diabetic mice. The specific delta-opioid ligands DPDPE and [D Ala2]deltorphin-II inhibited the binding of [125I]beta-endorphin whereas mu and kappa agonists did not. Therefore, the opioid receptor present in skeletal muscle fibers of the mouse is of the delta subtype and the number of these receptors is increased in type II diabetes in the mouse. PMID- 7784268 TI - Commentary on the Dunning tumor. PMID- 7784269 TI - Androgenic and antiandrogenic control on epidermal growth factor, epidermal growth factor receptor, and androgen receptor expression in human prostate cancer cell line LNCaP. AB - Both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor (AR). We studied the modification of the expression of epidermal growth factor (EGF), of its receptor (EGF-R), and of androgen receptor (AR) in the LNCaP cell line, under basal conditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked increase of EGF release was observed, completely blocked by the addition of OH-FLU. The Scatchard plot analysis of EGF-R binding revealed two classes of binding sites with high and low affinity. The administration of OH-FLU alone or combined with R1881 did not modify the affinity constants, while the low-affinity component disappeared after androgen administration. Both androgen and antiandrogen administration led to a significant increase of the EGF-R high affinity component. AR mRNA and protein levels were downregulated by R1881 treatment. Following OH-FLU administration, AR mRNA was slightly downregulated, and there was not a strict parallelism between AR mRNA levels and AR binding capacity. When combined with R1881, OH-FLU partially counteracted the androgen induced AR downregulation. Our data show that EGF-R binding capacity is the only parameter constantly raised in cell proliferation with respect to quiescent cells, and highlights the nonunivocal action of OH-FLU on androgen-induced effects. PMID- 7784270 TI - Inhibition of prostate cancer growth by estramustine and colchicine. AB - Hormone-refractory prostate cancer continues to be associated with a very poor prognosis. Agents that inhibit microtubule function have been found to be cytotoxic to prostate cancer cells in preclinical and clinical settings. It was the aim of this study to assess the activity of estramustine and colchicine, two microtubule inhibitors, in hormone-refractory prostate cancer. In clinically achievable concentrations, the combination of estramustine and colchicine was cytotoxic to both the Dunning rat prostate adenocarcinoma cell line MAT-LyLu (MLL) and human prostate cancer cells (PC-3). Microtubule function was assessed in vitro to evaluate possible mechanisms of action. In motility and cell cycle analysis assays, estramustine and colchicine inhibited cellular motility but not cell cycle transit. In vivo, these two agents both inhibited the growth of implanted Dunning rat prostate adenocarcinoma MLL cells but did not appear to have additive effects. The use of oral colchicine in the treatment of hormone refractory prostate cancer requires further investigation. PMID- 7784271 TI - Survival of patients with localized prostate cancer treated with percutaneous transperineal placement of radioactive gold seeds: stages A2, B, and C. AB - Between 1984 and 1991, a total of 177 patients with adenocarcinoma of the prostate were treated with transcutaneous, transperineal radioactive gold seeds. Of these 177 patients, 20 were determined to have pelvic lymph node involvement and were excluded from this review. The remaining 157 patients received a median radioactivity dose of 164 mCi with a median follow-up of 48 months. Cancer specific survival at 5 years was 100% for stage A2 and B1, 90% for stage B2, and 76% for stage C cancer. Covariates of grade, total radioactivity administered, age of the patient, and number of seeds implanted did not influence disease-free survival in a statistically significant manner. Significant complications were observed in two patients. The survival rates of patients treated with 198Au seed implantation for localized cancer are equivalent or better when compared to historical data of patients treated with 125I implantation, external beam radiotherapy, combination radioactive gold seed implantation and external irradiation, and radical prostatectomy. In addition, these comparable survival rates using interstitial 198Au seeds may be achieved with less morbidity. PMID- 7784272 TI - Components of a geriatric medical service: view from the UK. PMID- 7784273 TI - Urinary incontinence. PMID- 7784274 TI - Stroke prevention. PMID- 7784275 TI - Parkinson's disease. PMID- 7784276 TI - Alzheimer's disease. PMID- 7784277 TI - The role of ultrasound in the diagnosis of ganglion cysts. AB - Ganglion cysts are usually diagnosed clinically. We report three cases in which diagnostic doubt existed and in which ultrasound enabled the correct diagnosis to be made. PMID- 7784278 TI - Spectrum of renal cortical necrosis in acute renal failure in eastern India. AB - Renal cortical necrosis is an uncommon cause of acute renal failure. We report 23 cases of biopsy-proven renal cortical necrosis which constituted 6.3% (23/363) of all cases of acute renal failure studied over a period of seven years (1985-92). The patients were divided into two groups: obstetric and non-obstetric. Obstetric complications were responsible for renal cortical necrosis in 15 (65.2%) patients while non-obstetric conditions accounted for the remaining eight (34.8%) cases. The overall incidence of cortical necrosis in obstetric acute renal failure was 15/63 (23.8%) patients, the incidence being nearly equal in early (20.5%) and late (29%) pregnancy. Post-abortum renal failure was the sole cause of cortical necrosis in early pregnancy in the obstetric group. Haemolytic uraemic syndrome (three patients) and septicaemia (two patients) were the main cause of necrosis in the non-obstetric group. The cortical necrosis was diffuse and patchy in 17 and six patients, respectively. The disease had a fatal prognosis in 20 (87%) patients; mortality was due to uraemic complications and infections in the majority of patients. The high frequency of post-abortum renal cortical necrosis in our patients is similar to the experience of other Indian workers. PMID- 7784279 TI - Fractional excretion of potassium in normal subjects and in patients with hypokalaemia. AB - The aim of our study was the determination of fractional excretion of potassium (FEK+) in both normal subjects and hypokalaemic patients. Three hundred and twelve normal subjects aged 21-69 years and 84 hypokalaemic patients aged 36-72 years were studied. The mean FEK+ in normal subjects was 8% (range 4-16%). FEK+ was positively correlated with serum potassium (r = 0.74, p < 0.0001) and inversely with serum creatinine (r = -0.51, p < 0.001). The mean FEK+ in patients with hypokalaemia of external origin was 2.8% (range 1.5-6.4%). On the contrary, the mean FEK+ in hypokalaemic patients in whom renal potassium loss was the main aetiologic factor for the pathogenesis of hypokalaemia was 15% (range 9.5-24%). PMID- 7784281 TI - High dependency units in the UK: variable size, variable character, few in number. AB - An exploratory descriptive survey was conducted to determine the size and character of high dependency units (HDUs) in the UK. A telephone survey and subsequent postal questionnaire was sent to the 39 general HDUs in the UK determined by a recent survey from the Royal College of Anaesthetists; replies were received from 28. Most HDUs (82%, n = 23) were geographically distinct from the intensive care unit and varied in size from three to 13 beds, although only 64% (n = 18) reported that all beds were currently open. Nurse: patient ratios were at least 1:3. Fifty per cent of units had one or more designated consultants in charge, although only 11% (n = 3) had specifically designated consultant sessions. Junior medical cover was provided mainly by the on-call speciality term. Twenty units acted as a step-down facility for discharged intensive care unit patients and 21 offered a step-up facility for patients from general wards. Provision of facilities and levels of monitoring varied between these units. Few HDUs exist in the UK and they are variable in size and in the facilities and monitoring procedures which they provide. Future studies are urgently required to determine cost-effectiveness and outcome benefit of this intermediate care facility. PMID- 7784280 TI - Factors associated with high risk of marginal hyperthermia in elderly patients living in an institution. AB - The elderly, the very young, and the sick are known to be adversely affected by high environmental temperatures. In a retrospective open case-note review of 872 patients in a large institution during a hot summer we identified characteristics in the elderly that increase the risk of marginal hyperthermia. Women were more likely to be affected than men (25.6% vs 16.9%). We found an age-related increase in marginal hyperthermia, 15.7% of those below 60 years developed a hyperthermia compared to 18.9% in those between 70-79 years (non-significant), 28.3% in those between 80-89 years (p = 0.01) and 50% in those above 90 years (p < 0.01). There was also a direct relationship between the incidence of hyperthermia and the ambient temperature (29% in the warmer wards, compared to 17.2% in cooler ones; p < 0.01) and with the level of dependence (42.3% of the bedridden group, p < 0.01, and 20.4% of the semi-dependent, p < 0.01, compared to 11.1% of the mobile group). These factors were more significant as predictors of risk than the diagnosis. Identifying high risk patients early and taking appropriate measures to avoid hyperthermia and dehydration is important to try to decrease mortality during heatwaves. PMID- 7784283 TI - Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis? AB - Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective. PMID- 7784282 TI - Role of TSH measurements in predicting the outcome of treatment for Graves' disease following drug therapy. AB - Thyroid-stimulating hormone (TSH) levels obtained one month after the cessation of anti-thyroid drug treatment were assessed retrospectively for possible use in predicting outcome in 50 patients with a clinical diagnosis of Graves' disease. Thirty-four patients remained in remission at the end of the follow-up period and 16 patients relapsed. Although a TSH level of < 1.2 mU/1 did not discriminate between the two groups, none of the 24 patients who had TSH levels of > 1.2 mU/1 relapsed during the follow-up period, making early discharge from the thyroid clinic possible for these patients. PMID- 7784284 TI - Poisoning due to an over-the-counter hypnotic, Sleep-Qik (hyoscine, cyproheptadine, valerian). AB - The clinical features and risk of hepatotoxicity of 'Sleep-Qik' (valerian dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride 2 mg) were determined in 23 patients treated in our hospital between 1988 and 1991. The main clinical problems were central nervous system depression and anticholinergic poisoning. There was no clinical evidence of acute hepatitis in the 23 patients after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. Delayed onset of severe liver damage was excluded in 10 patients in whom a telephone follow-up was possible. However, subclinical liver dysfunction in the acute stage (onset after 12-24 hours) and in the intervening period after discharge from hospital could not be excluded. To establish the risk of hepatotoxicity in long-term users and in those taking an overdosage of valerian, a much larger study of longer duration with serial liver function tests is clearly needed. PMID- 7784285 TI - Iatrogenic Cushing's syndrome due to nasal betamethasone: a problem not to be sniffed at! PMID- 7784286 TI - Antiphospholipid syndrome in a patient with rapidly progressive fibrosing alveolitis. AB - The antiphospholipid syndrome is a thrombotic disorder which can occur in a primary form or more classically in systemic lupus erythematosus. An association between cryptogenic fibrosing alveolitis and the antiphospholipid syndrome has not previously been reported. We describe a patient with severe cryptogenic fibrosing alveolitis who developed pulmonary embolism and myocardial infarction in the presence of antiphospholipid antibody. The case also illustrates that worsening respiratory function may represent superimposition of one lung pathology on another, and may not simply be a deterioration of the pre-existing disease. PMID- 7784287 TI - Central pontine myelinolysis following orthotopic liver transplant: association with cyclosporine toxicity. AB - Central pontine myelinolysis can occur after orthotopic liver transplantation leading to high mortality and serious morbidity. In our case, central pontine myelinolysis was associated with wide fluctuations in cyclosporine levels during an episode of hypocholesterolaemia, which may have precipitated central pontine myelinolysis. PMID- 7784289 TI - Methotrexate-induced pericarditis and pericardial effusion; first reported case. AB - We report a case of methotrexate-induced pericarditis and pericardial effusion in a 22-year-old pregnant woman. These complications have not previously been described as isolated phenomena associated with methotrexate therapy. PMID- 7784288 TI - Post-thymectomy collapse: an unusual case of acute adrenal insufficiency. AB - A 54-year-old man who had an appearance strongly suggestive of Cushing's syndrome, collapsed after the removal of a carcinoid tumour of the thymus. The clinical suspicion of acute adrenal insufficiency was supported by invasive haemodynamic data and the diagnosis was subsequently confirmed biochemically. These post-operative events were subsequently ignored and a further crisis was probably prevented by tumour recurrence (and hence resumption of adrenocorticotropic hormone (ACTH) production). The ectopic production of ACTH from a carcinoid tumour of the thymus is recognised but a report of acute adrenal insufficiency from its removal is probably unique. PMID- 7784290 TI - The association of hereditary neuropathies and heritable skeletal disorders. AB - We describe two patients with associations of hereditary neuropathies and heritable skeletal disorders not previously reported. The first patient had Marfan's syndrome and hereditary motor and sensory neuropathy Type 1. The second patient had Ehlers-Danlos syndrome, Klippel-Feil syndrome and tomaculous neuropathy. PMID- 7784291 TI - Dysphagia in an HIV-positive man. AB - An HIV-positive man whose dysphagia was due to non-Hodgkin's lymphoma. The differential diagnosis of this symptom in the context of HIV infection is summarised in box 3. PMID- 7784293 TI - Wernike-Korjakoff syndrome due to hyperemesis gravidarum precipitated by thyrotoxicosis. PMID- 7784292 TI - Thiamine in Wernicke's syndrome--how much and how long? PMID- 7784294 TI - Peritonitis complicating leptospirosis. PMID- 7784295 TI - Lead preparations in Ayurvedic medicines. PMID- 7784296 TI - Streptococcus mitis causing epidural abscess. PMID- 7784298 TI - Giant chest wall arteriovenous malformation with spinal cord compression. PMID- 7784297 TI - Benign spontaneous pneumoperitoneum in an elderly patient treated medically with recovery. PMID- 7784299 TI - A negative skin biopsy for malignancy does not exclude the possibility of subsequent fatal disease. PMID- 7784300 TI - Fluctuating dementia and rhinorrhoea. PMID- 7784301 TI - Treatment with omega-3 fatty acid ethyl esters in hyperlipoproteinaemias: comparative studies on lipid metabolism and thrombotic indexes. PMID- 7784302 TI - Gastroprotective effect of aqueous extract of Cistus incanus L. in rats. AB - The antiulcer activity of a short-boiled aqueous extract from aerial parts of Cistus incanus was studied in rats against gastric lesions induced by necrotizing agents (1N HCl and absolute ethanol), indomethacin, serotonin and reserpine. The extract, containing bioflavonoids, was orally administered in the range from 0.25 to 0.50 g kg-1. It was found to have significant dose-related protective effects in all these experimental models, and was more effective against reserpine- and serotonin-induced mucosal congestion and haemorrhagic ulcers. These data suggest that the active constituents of the crude extract could be responsible for its protective effect by maintaining an efficient gastric mucosal microvascular supply. PMID- 7784303 TI - Protective effects of cilazapril against free radical injury in myocardial ischaemia-reperfusion. AB - Cilazapril is a prodrug which is rapidly hydrolysed to the pharmacologically active cilazaprilat following absorption to the bloodstream. In clinical pharmacological studies, administration of cilazapril resulted in potent, reversible, selective and competitive angiotensin converting enzyme inhibition. In this study, we have examined the protective effect of cilazapril on a myocardial ischaemia-reperfusion model by using different parameters of lipid peroxidation and protein oxidation. We have observed increased levels of diene conjugates, carbonyls and malondialdehyde as well as protein carbonyls after ischaemia-reperfusion, whereas protein sulphydryl groups were decreased. Our results clearly demonstrate that cilazapril, a non-sulphydryl, long-acting angiotensin converting enzyme inhibitor, has free-radical-scavenging potential in a model comparable to the clinical situation observed in humans. PMID- 7784304 TI - A modified liquid diet of chronic ethanol administration: validation by ethanol withdrawal syndrome in rats. AB - The validity of a modified liquid diet prepared from cow's milk, 7.2% ethanol, vitamin A and sucrose mixture has been investigated for chronic ethanol administration in rats. The rats fed by the modified liquid diet lost 3.8% of their body weight along 20 days. The mean ethanol consumption was in the range of 12.6 to 17.6 g kg-1 day-1. The blood ethanol level just before the withdrawal of ethanol was found to be 301.38 +/- 36.68 mg dl-1. A severe ethanol withdrawal syndrome was observed after 20-day exposure to ethanol in the modified liquid diet. The results suggest that the modified liquid diet can be used satisfactorily for chronic ethanol administration in rats. PMID- 7784305 TI - Regional differences in motor responsiveness to antimuscarinic drugs in rabbit isolated small and large intestine. AB - The pirenzepine-related analogue, nuvenzepine, and the antagonists selective for the three muscarinic receptor subtypes 4-DAMP (M1 and M3 receptors), pirenzepine (M1 receptors), methoctramine (M2 receptors) have been tested on rabbit isolated small and large intestinal regions provided with spontaneous motor activity. The employed drugs differently affected intestinal motility patterns. The ileum pendular movements as well as the proximal colon and taenia coli tone, spike amplitude and frequency were concentration-dependently inhibited by the compounds here employed. Their pIC50 values followed the rank order of potency generally reported for the involvement of the M3 muscarinic receptors (4-DAMP > or = atropine > nuvenzepine > or = pirenzepine > methoctramine). Unlike nuvenzepine and the other antimuscarinics assayed, the M1 selective antagonist pirenzepine, at nanomolar concentrations, was able to enhance the proximal taenia coli motility patterns suggesting that a M1-inhibitory pathway might operate in the physiological modulation of taenia coli motility. At variance with longitudinal ileum and colon contractile activity, proximal circular colon motility was resistant to muscarinic as well as to alpha 1-, H1-, 5-HT-blockade indicating that NANC neuronal mechanisms could act at this level. In summary, these data provide evidence that, at intestinal level, nuvenzepine is almost completely devoid of reliable M1-linked effect thus possessing a different pharmacological selectivity at muscarinic receptor subtypes with respect to pirenzepine. Furthermore, it emerges that rabbit spontaneous small and large intestinal motility is probably driven by different physiological mechanisms regional related. The peculiar circular colon refractoriness deserves further studies to be extended to the human tissue. PMID- 7784306 TI - Impact of drug dosage and brand on bioavailability and efficacy of praziquantel. AB - The efficacy of two brands (brand 1 = Biltricide; Bayer AG, Leverkusen, Germany; brand 2 = Distocide; EPICO pharmaceuticals, Cairo, Egypt) of praziquantel (PZQ) in full and half doses (40 and 20 mg kg-1) monitored as percentage egg reduction and cure rate was investigated in S. mansoni infected school-children. A total of 506 school-children (8-16 years of age) were classified into three groups according to their intensity of infection, heavy [> 500 eggs per grams (epg)], moderate (100-500 epg) and light (< 100 epg), after examination three stool samples (three slides per sample) on three consecutive days. Percentage egg reduction and cure rate were monitored 4 and 10 weeks post-treatment for each dose regimen in the different test groups. Before testing the efficacy of either bran in patients, the pharmacokinetic parameters of the two brands were studied in non-infected normal volunteers. Statistical analysis of the pharmacokinetic parameters of brand 1 vs brand 2 (in a dose of 20 or 40 mg kg-1) revealed no significant difference in elimination (ke), absorption rate constant (ka), elimination half life (t1/2e), area under the time-concentration curve (Auc), serum maximum concentration (Cpmax) and time to maximum concentration (Tmax). As regards the efficacy of test drugs, statistical analysis revealed that up to 10 weeks post-treatment the two brands of PZQ in full dose were equally effective in reducing egg count as their half doses except in heavily infected cases treated with brand 2 of PZQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784307 TI - Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen. AB - Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity. PMID- 7784308 TI - Protective effect of propionyl-L-carnitine against PAF-induced rat paw oedema. AB - Recent reports from our laboratory gave evidence showing that propionyl-L carnitine (PLC), unlike L-carnitine (LC) and acetyl-L-carnitine (ALC), has anti inflammatory activity in some models of vascular inflammation in rodents. The present paper shows that PLC (50 to 200 mg kg-1 i.p.) inhibits rat paw oedema induced by platelet activating factor (PAF), while LC and ALC, as well as indomethacin and phenylbutazone, are ineffective. The extent of the maximal inhibition produced by PLC at 200 mg kg-1 was comparable to that of betamethasone 0.05 mg kg-1 or sodium salicylate 100 mg kg-1. PLC inhibited also the early phase (1-2 h) of carrageenin-induced rat paw oedema, which is partly dependent on PAF release, but it was ineffective in the eicosanoid-dependent late phase (3-4 h) of the carrageenin oedema. We suggest that such anti-inflammatory activity of PLC may be due to various mechanisms converging on a stabilizing action upon biomembranes. PMID- 7784309 TI - Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats. AB - Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6 phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone. PMID- 7784311 TI - Management of dementia. PMID- 7784310 TI - Pharmacology of competitive inhibitors of HMG-CoA reductase. PMID- 7784312 TI - Child abuse--true or false? PMID- 7784313 TI - Anterior cruciate ligament injury. PMID- 7784314 TI - Multiple pathology in the elderly. PMID- 7784315 TI - Written papers. PMID- 7784316 TI - Dermatology. PMID- 7784317 TI - Skin surgery. PMID- 7784318 TI - Skin changes in systemic disease. PMID- 7784319 TI - Management of superficial fungal infections. PMID- 7784320 TI - Acne--general practice management. PMID- 7784321 TI - Atopic eczema. PMID- 7784322 TI - Hypertension and renal disease. PMID- 7784323 TI - Atypical pneumonias. PMID- 7784324 TI - A radical review of antenatal care? PMID- 7784325 TI - Communication and cooperation. PMID- 7784326 TI - Management of peptic ulcer. PMID- 7784327 TI - Rheumatology symposium. PMID- 7784328 TI - Rheumatology symposium. PMID- 7784329 TI - A contraindication to HRT. PMID- 7784330 TI - Transfollicular drug delivery. AB - The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both localized and systemic drug delivery. Greater understanding of the structure and function of the hair follicle may facilitate rational design of drug formulations to target follicular delivery. Targeted drug delivery may enhance current therapeutic approaches to treating diseases of follicular origin. Presented here is a review of follicular drug delivery and a discussion of the feasibility of the pilosebaceous unit as a target site. PMID- 7784332 TI - Physical entrapment of adriamycin in AB block copolymer micelles. AB - The entrapment of Adriamycin (ADR) in micelles composed of AB block copolymers (poly(ethylene oxide-co-beta-benzyl L-aspartate) (PEO-PBLA)) was investigated. The loading process involved transfer of ADR and PEO-PBLA into an aqueous milieu from dimethylformamide (DMF) through a dialysis procedure. Evidence for the physical entrapment of ADR in the polymeric micelles was derived from fluorescence spectroscopy and gel permeation chromatography (GPC). The total fluorescence intensity of ADR was low, suggesting that the drug was self associated in the micelles. In addition, quenching experiments, using a water soluble quencher (iodide (I-)), showed that the fluorescence of ADR present in micellar solutions was largely unaffected by I-, whereas the fluorescence of free ADR was readily quenched. From Stern-Volmer plots, quenching constants (KSV) of 2.2 and 17 M-1 were determined for ADR in micellar solutions and free ADR, respectively. As a result of the entrapment of ADR in the micelles, ADR binds only slightly serum albumin as evidenced by GPC. In contrast, ADR readily binds serum albumin in aqueous solutions. The findings suggest that ADR is stably entrapped in PEO-PBLA micelles. ADR entrapment in polymeric micelles is expected to affect markedly the pharmacokinetics of ADR. PMID- 7784331 TI - Synthesis and pharmacological properties of 2-[S-acetylthiorphan]-1,3- diacylaminopropan-2-ol derivatives as chimeric lipid drug carriers containing an enkephalinase inhibitor. AB - The design of 1,3-dacylaminopropan-2-ols as CNS-directed carrier groups is based on their resemblance to endogenous lipids and the properties of pseudotriglyceride esters to facilitate the brain penetration of therapeutic agents. 2-[S-acetylthiorphan]-1,3-diacylaminopropan-2-ols, differing from the nature of 1,3-acyl chains, were synthesized and evaluated in vivo using the hot plate jump test. The compounds exhibited naloxone reversible analgesic properties. The effects were superior to those of parent compounds thiorphan and S-acetylthiorphan. The palmitoyl derivative showed also activity at 0.8 mmol/kg after oral administration. Like acetorphan, a thiorphan prodrug, these compounds were poor substrates for brain enkephalinase, suggesting the release of the pharmacological active inhibitor at the site of action in the brain. PMID- 7784333 TI - Construction of an intermittent-motion capsule filling machine simulator. AB - A pneumatically operated apparatus is described which simulates the forces generated by and the component movements encountered in a Macofar 13/2 dosator type capsule filling machine. Force transducers are fitted to the dosing piston and dosator tip, and the movement of the dosator piston and the powder bed followed by displacement transducers. Calibration of the transducers is described. The output from the transducers is collated, stored and manipulated by microcomputer. The manufacturing parameters which can be studied using this apparatus are discussed. PMID- 7784334 TI - Preparation and physicochemical characterization of aqueous dispersions of coenzyme Q10 nanoparticles. AB - The present study describes a novel pharmaceutical formulation of coenzyme Q10, viz. submicron-sized dispersions of the substance prepared by emulsification of molten coenzyme Q10 in an aqueous phase. Photon correlation spectroscopy reveals mean diameters of 60 to 300 nm depending on process parameters. Coenzyme Q10 nanoparticles remain stable on storage for more than 30 months. Lipophilic drugs can be incorporated into the nanoparticles demonstrating their potential use as a drug carrier system. Transmission electron micrographs of freeze-fractured replica show spherical particles with an amorphous core. Cryo-electron microscopy reveals the coexistence of small unilamellar vesicles in phospholipid stabilized dispersions. Thermoanalysis and X-ray studies indicate that the dispersed and emulsified coenzyme Q10 does not recrystallize even at 4 degrees C over 30 months. These agree with 1H NMR data which demonstrate that coenzyme Q10 molecules have a high mobility when formulated as nanoparticles and that colloidally dispersed coenzyme Q10 remains in the state of a supercooled melt. Despite the high melting point of the bulk material, coenzyme Q10 dispersions represent no suspensions but O/W emulsions according to the IUPAC definition (1). PMID- 7784335 TI - Design for cell-specific targeting of proteins utilizing sugar-recognition mechanism: effect of molecular weight of proteins on targeting efficiency. AB - Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine gamma-globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2 methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70-80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784336 TI - Stabilization of chimeric BR96-doxorubicin immunoconjugate. AB - Chimeric BR96-doxorubicin conjugate (BR96-DOX) is an immunoconjugate designed to specifically target and kill certain tumor cells. The linker between the chimeric BR96 antibody and DOX is an acid-labile hydrazone group which was designed to undergo lysosomal hydrolysis to release DOX in vivo. Stability studies indicated that acid-catalyzed hydrazone hydrolysis was the major degradation route in vitro. Even under optimal conditions of pH and temperature, the stability of BR96 DOX in solution was not acceptable for long-term storage. Lyophilization of BR96 DOX in the presence of added sugars, such as lactose or sucrose, and subsequent storage of the lyophile under refrigeration significantly improved the stability. Therefore lyophilization appears to be a viable approach for achieving long-term stabilization of BR96-DOX. PMID- 7784337 TI - Efficacy evaluation of a novel submicron miconazole emulsion in a murine cryptococcosis model. AB - Submicron emulsions of miconazole were stabilized by using a combination of three emulsifiers comprising phospholipids, poloxamer, and deoxycholic acid (DCA). The presence of DCA was vital for prolonged emulsion stability owing to its contribution to the elevated zeta potential of the emulsion. Further, the results by the phospholipid surface labelling colorimetric technique clearly suggested that poloxamer molecules interacted with phospholipid polar-head groups of the mixed DCA-phospholipid interfacial film, resulting in the stabilization of the emulsion by a steric enthalpic entropic mechanism. The plain emulsion vehicle was well tolerated up to a dose of 0.6 ml injected i.v. to BALB/c mice. The maximum tolerated dose of miconazole was 80 and 250 mg/kg in Daktarin i.v. (a marketed product) and emulsion, respectively, showing an improved safety ratio of 1 to 3 in favor of the emulsion. These results tended to confirm that the adverse effects associated with Daktarin i.v. injection should be associated with the vehicle rather than with the miconazole itself. In a murine cryptococcosis model, only one mouse out of ten remained alive by day 15 in the infected group treated with Daktarin i.v., while in the miconazole emulsion treated group, mice began to die from day 16 up to day 25 post inoculation. Thus, the multiple-dose treatment with the miconazole emulsions improved the protection offered to the infected mice. However, the therapeutic levels of miconazole that were reached in the target organ (brain) were lower than those required for complete eradication of Cryptococcus neoformans, which is known to multiply preferentially in the brain. PMID- 7784338 TI - Comparison of gamma scintigraphy and a pharmacokinetic technique for assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler. AB - A comparison has been made of pulmonary deposition of terbutaline sulphate from a pressurized metered dose inhaler (pMDI), measured in 8 healthy male subjects by gamma scintigraphy and by a pharmacokinetic (charcoal-block) method, involving drug recovery in urine. Measurements were carried out with a pMDI at slow (27 l/min) and fast (151 l/min) inhaled flows and with Nebuhaler large volume spacer device (average inhaled flow 17 l/min). Overall, the two methods did not differ significantly in their estimates of whole lung deposition, although values obtained by gamma scintigraphy exceeded those from the charcoal-block method for the pMDI with fast inhalation. The regional distribution of drug within the lungs and deposition in the oropharynx could be assessed by gamma scintigraphy, but not by the charcoal-block method. It is concluded that either method may be used to assess whole lung deposition of terbutaline sulphate from pMDIs, both with and without a spacer, although each method has its own inherent advantages and disadvantages. PMID- 7784339 TI - Estimation of agitation intensity in the GI tract in humans and dogs based on in vitro/in vivo correlation. AB - In this study, we assessed the hydrodynamic flow around a dosage form in the GI tract in humans by comparing the characteristics of in vitro and in vivo release of two different types of controlled release acetaminophen (paracetamol) tablets, A and B. The former tablet showed an agitation speed-dependent release at a high speed range (50-100 rpm), whereas the latter showed this characteristic at a low speed range (10-50 rpm). The mean release amount-time profiles of tablets A and B in humans showed biphasic characteristics, and the first phase of the absorption profiles of A and B was close to their in vitro profiles at a paddle speed of 10 rpm. The in vivo profiles were also superimposable on in vitro dissolution curves obtained by the flow-through cell method at a flow rate of 1 mL/min (velocity 0.89 cm/min) or less. These results indicate that the hydrodynamic flow around the dosage forms in the human GI tract could be extremely low. The in vivo release rate of these tablets in dogs was greater than in humans, and was estimated to be equivalent to the release rate determined by the paddle method at 100 rpm. This indicates that a higher agitation intensity in the GI tract in dogs than in humans may be one cause of the discrepancies between humans and dogs in drug absorption studies. PMID- 7784340 TI - In vivo evaluation of a colon-specific drug delivery system: an absorption study of theophylline from capsules coated with azo polymers in rats. AB - Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N'-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coating for colon-specific drug delivery. The gastrointestinal absorption of theophylline from capsules coated with the azo polymers was examined in the proximal part of the small intestine and the cecum of male Wistar rats. The capsules were surgically inserted in the region of interest. The plasma concentration of the drug was higher when the capsules were inserted in the cecum as compared to the small intestine. The appearance of theophylline in the plasma when capsules were administered in the small intestine can be attributed to simple diffusion of the drug through the swollen polymer coating. Release and absorption from the cecum is the combined results of diffusion and degradation of the azo polymer coatings by bacterial azo reductase. PMID- 7784341 TI - Drug transport across nylon 610 films: influence of synthesis variables. AB - Nylon 610 is a hydrophilic polymer with considerable potential as a membrane for drug microencapsulation. To better understand drug transport through such membrane, the influence of the solvents and monomers used in the synthesis of nylon films were examined using a full factorial study. Nylon 610 films were synthesized by an interfacial polycondensation reaction using hexamethylenediamine (HD) in the water phase and sebacoyl chloride (SC) in the organic phase, which was a solvent blend of chloroform and trichlorotrifluoroethane at ratios of 1:1, 1:4, and 4:1. Monomer concentrations studied were 0.2, 0.4, and 0.6 M with respect to their appropriate phase, while the monomer ratios were 1:1, 3:1, and 1:3. The molecular weight, porosity, thickness, and crystallinity of the films were characterized. The transport of potassium chloride, hydrocortisone, and m-cresol was studied at 25 degrees C as a function of the synthesis variables. Potassium chloride was selected to measure the porosity of the membrane. Hydrocortisone and m-cresol, a known solvent for nylon 610, were used to study pore and solution-diffusion transport, respectively. The molecular weight of the films was proportional to the chloroform concentration. As the molecular weight increased, film thickness, porosity, and hydrocortisone permeability increased. As the molecular weight decreased, film thickness and porosity decreased, while m-cresol permeability increased. These results can be explained on the basis of HD ability to readily partition into a good solvent such as chloroform permitting high molecular weight polymer to form before precipitation. PMID- 7784342 TI - Effect of norfloxacin on theophylline disposition: a comparison with other fluoroquinolones. AB - The effects of norfloxacin (NOR), at steady-state plasma concentrations of 0-32 mg.l-1, on the plasma clearance of a 6 mg.kg-1 i.v. bolus dose of theophylline (THEO) in the male Sprague-Dawley rat have been studied. The effects were characterised by a Ki value (Ki = 12 microM), which was comparable with Ki values obtained previously under identical conditions for ciprofloxacin, but higher than that obtained for enoxacin. The distributional characteristics, volume of distribution and liver to plasma concentration ratio, were very similar for the three compounds. The only marked pharmacokinetic differences were in hepatic clearance, where there was a rank order NOR > ciprofloxacin > enoxacin, a reverse of the order in the reduction of THEO clearance seen in clinical studies. The advantages of using the steady-state experimental design described here are that equivalent concentrations are utilised to compare related drugs and differences in pharmacokinetics are accounted for, to allow a direct comparison of potency. This information, together with additional pharmacokinetic considerations, suggests that the different effects on THEO clearance seen in the clinic for NOR, ciprofloxacin and enoxacin are not solely due to differences in inhibitory potency, but also involve differences in hepatic clearance and hence systemic availability of the fluoroquinolones. PMID- 7784343 TI - Incorporation of first-order uptake rate constants from simple mammillary models into blood-flow limited physiological pharmacokinetic models via extraction efficiencies. AB - Incorporation of First-Order Uptake Rate Constants from Simple Mammillary Models into Blood-Flow Limited Physiological Pharmacokinetic Models via Extraction Efficiencies. W. L. Roth, L. W. D. Weber, and K. Rozman (1995). Pharm. Res. 263 269. First-order rate constants obtained from classical pharmacokinetic models correspond to mammillary systems in which all of the blood (or plasma) is assumed to be located in a central compartment. In such models the rate at which chemicals are transported out of this pool and into another compartment is the product of the mass of chemical in the central compartment multiplied by a rate constant, which is not limited in magnitude by the blood flow, or the rate at which chemicals from the blood are delivered to the peripheral compartment. Most of the physiologically-based models published to date dispense with some of the information available from mammillary models by assuming that all of the chemical delivered by the flow of blood rapidly equilibrates and can be taken up by the tissue under the control of a "partition coefficient" (Rij = Cj/Ci). We show that the partition coefficient alone does not retain the uptake rate (kji) information available from a classical mammillary model, but that the uptake rate information can be incorporated via unitless extraction efficiency parameters, epsilon j. PMID- 7784344 TI - Pharmacokinetic study of zeolite A, sodium aluminosilicate, magnesium silicate, and aluminum hydroxide in dogs. AB - Zeolite A is a synthetic zeolite which may have therapeutic utility in osteoporotic individuals because of its ability to stimulate bone formation. A study of Zeolite A (30 mg/kg), sodium aluminosilicate (16 mg/kg), magnesium trisilicate (20 mg/kg), and aluminum hydroxide (675 mg) was designed in beagle dogs. The purpose of this study was to compare the oral bioavailability of silicon and aluminum from Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide in dogs. Twelve female dogs received each compound as a single dose separated by one week in a randomized, 4-way, crossover design. Plasma samples were drawn at time 0 and for 24 hours after dosing. The concentrations of silicon and aluminum were determined by graphite furnace atomic absorption. The mean plasma silicon AUC values (+/- S.D.) were 9.5 +/- 4.5, 7.7 +/- 1.6, 8.8 +/- 3.0, 6.1 +/- 1.9 mg.hr/L and the mean plasma silicon Cmax values (+/- S.D.) were 1.07 +/- 1.06, 0.67 +/- 0.27, 0.75 +/- 0.31, 0.44 +/- 0.17 mg/L for Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide respectively. Although mean silicon AUC and Cmax values were elevated when compared to baseline after administration of the silicon containing compounds, only the AUC from Zeolite A reached statistical significance (p = 0.041). The mean plasma silicon Tmax values (+/- S.D.) were 7.9 +/- 6.4, 5.8 +/- 4.6, 6.9 +/- 6.3 and 8.5 +/- 3.4 hrs for Zeolite A, sodium aluminosilicate, magnesium trisilicate and aluminum Hydroxide respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784345 TI - Comparative tissue distribution and elimination of amphotericin B colloidal dispersion (Amphocil) and Fungizone after repeated dosing in rats. AB - The pharmacokinetic profiles of amphotericin B (AmB) after administration of Amphocil, an AmB/cholesteryl sulfate colloidal dispersion (ABCD) and the micellar AmB/deoxycholate (Fungizone) were compared after repeated dosing in rats. After administration of ABCD and Fungizone at an equal AmB dose (1 mg/kg), AmB concentrations in plasma and most tissues were lower for the ABCD dose, especially in the kidneys where reduced drug concentration correlated with reduced nephrotoxicity. In contrast, AmB concentrations in the liver were substantially higher when ABCD was administered; however, without an accompanying increase in hepatotoxicity. Daily administration of ABCD for 14 days did not lead to AmB accumulation in plasma; while a slight accumulation was observed after multiple administration of Fungizone. AmB was eliminated more slowly from the plasma and various tissues and urinary and fecal recoveries of AmB were reduced after ABCD administration. These results suggest that ABCD may be stored in tissues in a form that is less toxic and is eliminated from the systemic circulation by a different mechanism than the free and protein-bound AmB in plasma. AmB accumulation in the spleen was observed when higher, doses of ABCD (5 mg/kg) were administered, which could be due to saturation of hepatic uptake of AmB. Comparison of spleen concentrations of AmB between ABCD and Fungizone at 5 mg/kg AmB doses was not possible because of Fungizone's toxicity in rats. In all other organs, AmB concentrations reached or approached a steady state within two weeks of dosing with ABCD. Urinary and fecal clearences of AmB were not different between ABCD and Fungizone administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784346 TI - Age-dependent intestinal absorption of valproic acid in the rat. AB - The absorption of valproic acid (VPA) across isolated perfused segments of jejunum, ileum and colon was examined in situ in 14-day- to 24-month-old Fischer 344 rats. Within each age group, the intrinsic absorptive clearance (Cla) of VPA at a perfusate concentration of 1 mg/ml was highest in the jejunum, lowest in the colon, and intermediate in the ileum. When intestinal Cla was normalized for the dry weight of the segment, within-group variability decreased. In all segments, VPA Cla normalized by dry weight decreased during development (< or = 20 to 90 days) and remained relatively constant during aging (90 days to 24 months). The mechanism of valproate absorption (active vs. passive) was examined across age in everted intestinal sacs prepared from each of the three segments. Data were consistent with active transport of VPA in the jejunum and ileum of rats of all ages, and in the colon of pre-weanling animals. Colonic absorption of VPA appeared to occur by passive diffusion in adult rats. In contrast, colonic absorption of d-glucose occurred, only by passive diffusion in all age groups. These data indicate that, during development, significant alterations in the rate of VPA absorption occur throughout the rat intestine. Furthermore, while active transport of VPA by the small intestine was present throughout the age range investigated, active transport by the colon became negligible by the time of weaning. PMID- 7784348 TI - Estimation of impurity profiles of drugs and related materials. 12. Isolation and identification of an isomeric impurity in danazol. AB - We report on a new isomeric impurity of danazol. This impurity designated as isodanazol was detected by reversed-phase high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Its structure was determined after separation by preparative HPLC. Mass spectrometry revealed the isomeric nature of the impurity while the UV spectrum indicated profound difference in the isoxazole moieties. The structure of the isomeric isoxazole ring in isodanazol was determined by NMR spectroscopy using COSY, HETCOR and NOE measurements. The difference between the UV spectra of danazol and isodanazol is explained on the basis of the difference between the aromaticities of their isoxazole rings supported by quantum chemical calculations. The quantitative determination of the impurity down to the 0.05% level can be performed by HPLC, gas chromatography and TLC densitometry. PMID- 7784347 TI - Microdialysis sampling to determine the pharmacokinetics of unbound SDZ ICM 567 in blood and brain in awake, freely-moving rats. AB - The free concentrations of the serotoninergic 5-HT3 antagonist SDZ ICM 567 in blood and in the central nervous system were examined in awake, freely-moving rats using blood and brain microdialysis coupled to liquid chromatography. Microdialysis probes were implanted in the jugular vein and in the frontal cortex and dialysis samples were simultaneously collected from both sites. Pharmacokinetic parameters were calculated after a 10 mg/kg intravenous dose of [14C]SDZ ICM 567. The elimination half lives measured in whole blood, brain and blood microdialysates were similar (congruent to 1.7 h). The AUC0-5h corresponding to the unbound drug was 462 +/- 142 ng.ml-1.h in blood dialysate, not significantly different from the AUC corresponding to the free concentration in whole blood, i.e. 586 +/- 63 ng.ml-1.h. The free fraction in blood obtained in vitro by equilibrium dialysis (21%) or by microdialysis (19%) was not statistically different from that obtained in vivo (17%) in microdialysis experiments. The unbound concentrations (AUC0-5h) of SDZ ICM 567 in the brain cortex were 86 +/- 24 ng.ml-1.h, lower than those expected from unbound blood concentrations, suggesting an active transport out of the central nervous system. Finally, microdialysis sampling allowed the determination of pharmacokinetic parameters of SDZ ICM 567 in blood and brain as well as the estimation of the free fraction of drug in blood. PMID- 7784349 TI - Changes in solid-state structure of cyclophosphamide monohydrate induced by mechanical treatment and storage. AB - The effects of mechanical treatment and various storage conditions on the structure of cyclophosphamide monohydrate were evaluated by thermal and X-ray analyses and molecular modeling. The monohydrate form of cyclophosphamide was found to convert to the anhydrous form through a metastable phase. Metastable forms were produced by mechanical treatment and by desiccation. These forms could be detected in differential scanning calometric thermograms as endothermic peaks, at approximately 39 degrees C, and X-ray powder diffractometric analysis, e.g.; by a characteristic reflection at 15.3 degrees (2 theta). Molecular modeling was used to study molecular interactions and putative metastable structures. The dehydration enthalpies of the cyclophosphamide monohydrate obtained from quantum chemical calculations and DSC analysis were 51.6 and 36.1 J/g, respectively. In a unit cell of the stable monohydrate, a water molecule is held by O(7) of the cyclophosphamide molecule and N(6)H of a neighboring cyclophosphamide molecule, with hydrogen bonds enabling existence of a water tunnel. The metastable form of cyclophosphamide is detected when a sterically formed block in the possible tunnel is removed, and the water molecules are allowed to leave the system one by one. PMID- 7784350 TI - Chemical pathways of degradation of the bradykinin analog, RMP-7. PMID- 7784351 TI - Differential expression of the phenol family of UDP-glucuronosyltransferases in hepatoma cell lines. PMID- 7784352 TI - Pharmacokinetics of caffeine and its demethylated metabolites in lactation: predictions of milk to serum concentration ratios. PMID- 7784353 TI - Structural requirements for interaction with the oligopeptide transporter in Caco 2 cells. PMID- 7784354 TI - [Patient admission to a child and adolescent psychiatric polyclinic. Referral, patient information, preparation, concepts, expectations and fears of children, adolescents and their parents]. AB - This study investigates 77 families i.e. their children, aged 7-17, and their parents, who attended the out-patient clinic of the child psychiatric department for the first time. It was intended to examine and outline the subjective situation on entering the clinic. A structured verbal interview was conducted with the children before the start of the actual examination procedure, while a written questionnaire was submitted to the parents. Among the questioned items were modes of referral, references, sources of information, knowledge and preparedness, ideas, expectations and apprehensions about the institution and its treatments. The answer that were obtained reflected a lack of self-determination on the part of the children and the strength of influence exerted by the parents along with other relevant authorities. The children were often taken to the clinic without any active consent on their part. When asked about hopes of improvement they did not often confirm. Similarly fears about the impending examination were at first denied by most children but subsequently conceded, when concrete suggestions were made. Strikingly the better informed and prepared, children were able to admit to their fears more often. The results of the parental questionnaire illustrate an extensive lack of information about the institution that the families were actually attending. It may be concluded that the parents had also been little assertive when preparing their children for the examination. When asked about their expectations the parents primarily quoted "help" and "advice". Scepticism about the examination came only at the bottom of the list.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784355 TI - [Is there an end to adolescence?--Observations from the ethnopsychoanalytic viewpoint]. AB - Being an adult today does not mean anymore to have secure knowledge and routine at one's disposal, but rather being able to endure anxiety and uncertainty in culture. In the course of the process of civilization youth has more and more become the model and embodiment of a dynamic, ever-changing culture. As a consequence of abolishing initiation rituals, which originally determined the transition to adulthood, adolescents today must develop their own strategies in order to relate chaos and order to each other. The antagonism between family and culture plays a central role here: The individual must be able to personify two aggregate states as it were, that is being firm in the family and being fluid in culture. Today adolescence only ends inside the family when the individual takes on a parent role, but in the cultural area we should remain adolescents all of our lives, in order to muster the creativity necessary for a changing culture. PMID- 7784356 TI - [The inpatient routine as a therapeutic community: multiprofessional treatment concept within the scope of a child psychiatric day care clinic]. AB - The article will describe a multiprofessional (nurses, social workers, teachers, psychologists, physicians) treatment in a child psychiatric daycare-clinic. In that context the importance of relationship as an equivalence to the "primary motherliness" for early-disturbed children will be stressed. Further the article will focus on the relevance of continuous "post-education" and the broadening of the children's cognitive range by way of this object relation. Also, the article will inform about the uncovering psychotherapy with the children and their parents and about the importance of informations both from the therapists to the team as the other way round. Based on case studies it will be demonstrated how the multiprofessional team functioning as a "whole object" becomes instrumental for patients to work through affective relationships and mechanisms of defence. PMID- 7784357 TI - [Diagnosis of performance anxiety in educational spelling tests: new results of the psychometric properties and validity of a relevant brief scale]. AB - In the present study the psychometric properties and the criterion-related validity of a short scale for measuring students' spelling-specific test anxiety were analyzed. This scale consists of 13 self-rating items which reflect students' worry and emotionality reactions in face of spelling requirements at school. Along with some concurrent criterion variables (such as general self esteem, academic and spelling-related self-concept, and spelling-related attributions, spelling and mathematics achievement, regressive classroom behavior), data were gathered at the beginning (N = 274) and, nearly 11 months later, at the end (N = 257) of the school year. At both measurement times, principal component analyses correspondingly revealed one common test anxiety factor and led to an overall scale format. This final scale solutions appeared to be sufficiently reliable and stable. Furthermore, their relationships to the various criterion variables largely turned out as theoretically expected. Especially, the spelling-specific test anxiety scores could be best predicted by spelling-specific self-concept and by spelling achievement, respectively. Thus, the findings of the present study could replicate the results of a previous pilot study and provided further support for the construct validity of interpretations based upon the spelling-specific test anxiety scale. PMID- 7784358 TI - [Aspects of pediatric psychotherapy with children and adolescents with uncontrolled aggressive behavior]. AB - Starting from theoretical psychodynamic preliminary thoughts concerning the symptomatics of aggressive-uncontrolled behavior of children and adolescents, aspects of practical childpsychotherapeutic treatment processes are described. The latter is described as being dependent from the individual level of development of each child. Since it is usually the case that children and adolescent with these symptoms are psycho-socially immature based on ego structural deficits at the beginning of treatment, the therapist primarily has the function of a transition object in accordance with Winnicott in the therapeutic beginning phase. Since the communication possibilities of these children are situated mostly on a deep nonverbal level of affectively loaded patterns of interaction in the beginning, the affective 'answer' of the therapist is of primary importance at this stage. In later stages of increased ego maturity symbolic communication possibilities increasingly open, whereby the child's conflicts can be worked through, shifted to play and shaping objects. PMID- 7784359 TI - [Prolegomena on transcultural pediatric psychotherapy]. AB - In a first step the concept of "transcultural child psychotherapy" is explained. Based on an analysis on the demand for a transcultural child psychotherapy in Germany the necessity for its development is pointed out. Names of institutions and persons suitable for transcultural child psychotherapy are given. A systematic attempt follows to integrate the transcultural point of view into general strategies and intervention techniques of child psychotherapy, stressing the psychoanalytical, client-centered and behaviour therapeutic approach. Specific problems as non-verbal, verbal and diagnostic aspects in transcultural child psychotherapy as well as toys are briefly mentioned. Problem groups of a special interest of a transcultural child psychotherapy (e.g. asylum seeking, migrant, persecuted, sold, and adopted children) are mentioned and pointed out to as specific risk groups. The essay ends with questions regarding the effectiveness of transcultural child psychotherapy and with an outlook into further research activities. PMID- 7784360 TI - [Sexual abuse by staff of inpatient facilities for children and adolescents]. AB - Examples of sexual abuse by professionals in residential agencies for children are presented as well as aspects of sexual attraction between staff members and children which is put under taboo among professionals. The author focuses on incestuous and sexual abuse supporting institutional structures: a) rigid and authoritarian structures, which contribute to the emotional isolation of staff members and b) unstructured and diffuse leadership. Indications are given for staff members who suspect colleagues of sexual abuse of children. PMID- 7784361 TI - An audit of trisomy 16 in man. AB - Sufficient information is now available from the literature to produce an audit of trisomy 16, in a theoretical cohort of 100,000 recognized pregnancies, from gametogenesis to term and onwards. Recent reports of premature separation of chromosome 16 bivalents during maternal meiosis I provide a novel mechanism for generation of this aneuploidy. Most, if not all, errors resulting in recognized mosaic and non-mosaic trisomy 16 pregnancies investigated using polymorphic DNA markers appear to originate at that stage. The incidence of this maternally derived trisomy 16 in the late first trimester is equivalent to 1500 cases in 100,000 recognized pregnancies, a figure which now corresponds very closely to the reinterpreted oogenesis data. Most trisomy 16 pregnancies are lost around 12 weeks' gestation, but of the order of 10 per cent (120-150 in this audit) undergo reduction to disomy, with 30 of these excluding aneuploidy from the fetal cell lineage (trisomic zygote rescue) and continuing into the second trimester. Maternal uniparental disomy (UPD) in one-third of this latter group is associated with loss later in pregnancy or severe intrauterine growth retardation, but can be compatible with a viable pregnancy. Adverse pregnancy outcomes are not restricted to those with UPD. Analysis of reports of confined placental mosaicism for chromosome 16 without associated UPD indicates that the presence of high levels of trisomic cells in the placenta alone consistently produces a more variable inhibition of fetal growth, which may also, in cases, be associated with late pregnancy loss. PMID- 7784362 TI - An accessory marker derived from chromosome 20 and its co-existence with a mosaic trisomy 20 cell line. AB - We report a 16-month-old boy with delayed psychomotor development, dysmorphic features, and failure to thrive. He had a mosaic karyotype detected prenatally: mos 46,XY/47,XY, +r(20)/47,XY, +20. After birth, the abnormal cell lines were confirmed in a number of tissues. The small ring chromosome was identified using fluorescence in situ hybridization as derived from chromosome 20. We compared our patient with previously reported cases of mosaic trisomy 20 detected prenatally and associated with an abnormal phenotype. In an attempt to characterize an r(20) syndrome, we also compared our case with two similar reports in the literature. PMID- 7784363 TI - Prenatal diagnosis of neurofibromatosis type 1: from flanking RFLPs to intragenic microsatellite markers. AB - Even though the neurofibromatosis type 1 (NF1) gene was cloned more than 3 years ago, the process of identifying mutations has not been fruitful, and genetic counselling is mainly based on the use of linked markers. Since 1990, we have analysed 130 NF1 families and have performed six prenatal diagnoses. In each case, genetic counselling has relied on linked markers and informativity was achieved in all of them. The use of intragenic microsatellite polymorphisms (IVS27AAAT2.1, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0) has increased the informativeness in our series of NF1 families to an average of 90 per cent, providing accurate diagnosis and confirmation of the disease status. PMID- 7784364 TI - Early prenatal diagnosis of cartilage-hair hypoplasia (CHH) with polymorphic DNA markers. AB - Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder resulting in short stature and hypoplasia of hair. Associated features include impaired T-cell mediated immunity, deficient erythropoiesis, gastrointestinal dysfunction, and an increased risk of malignancies. As the condition may, in some cases, be severe or even fatal during childhood, families with a previous history of CHH may wish to have prenatal diagnosis. We have previously assigned the gene for CHH to the proximal 9p by linkage analysis using several polymorphic DNA markers. Here we report the prenatal testing for CHH in three Finnish and one Australian family using three DNA markers closely linked to the CHH gene. In three cases a fetus unaffected with CHH was predicted at the probability level of more than 94 per cent. In one case, an affected fetus was predicted. The results were in concordance with ultrasonography performed for all fetuses. The three children born to date were unaffected as predicted. The DNA marker-based analysis thus provides a useful method for early prenatal testing for CHH. PMID- 7784365 TI - Rapid fetal karyotype from cystic hygroma and pleural effusions. AB - Fluid from pleural effusion (n = 2) and cystic hygroma (n = 7) was obtained from eight fetuses, between 13 and 32 weeks of pregnancy at the time when a conventional prenatal diagnosis procedure was carried out. As these fluids contain lymphocytes, they were processed like peripheral blood. A karyotype was obtained in 4 days in both cases of pleural effusion and in four out of seven samples of cystic hygroma. An abnormal karyotype was detected in three of the four samples of cystic hygroma: two trisomies 21 and a monosomy X. Different parameters were evaluated in order to predict the feasibility of obtaining a cytogenetic diagnosis. Our data showed that if the amount of fluid obtained was > or = 4 ml and the initial lymphocyte count (ILC) was > 0.2 x 10(6) cells/ml, a cytogenetic diagnosis was possible from an initial concentration of cultured lymphocytes (ICCL) of > 0.06 x 10(6) cells/ml. PMID- 7784366 TI - Fetal erythroblasts from maternal blood identified with 2,3-bisphosphoglycerate (BPG) and in situ hybridization (ISH) using Y-specific probes. AB - Different types of fetal nucleated cells can be found in maternal blood, providing the possibility of non-invasive prenatal diagnosis. For this purpose, we have studied fetal erythroblasts. We discovered that haemoglobin-containing cells treated with 2,3-bisphosphoglycerate (BPG) can be visualized by a peroxidase reaction, which at the same time visualizes an in situ hybridization (ISH) signal, specific for the X, Y or 21 chromosome. In order to prove that the BPG-positive cells were erythroid, an anti-glycophorin A (GPA) antiserum combined with a staphylococcal rosette technique was used. To enrich for erythroblasts, leukocytes were depleted from maternal blood by treatment with anti-CD45 monoclonal antibody and passage over an anti-mouse IgG-coated glass bead column. To evaluate the potential of the method for clinical use, we studied maternal blood samples from 18 women referred to us for prenatal diagnosis between 6 and 19 weeks of gestation. Erythroblasts were found in 13 out of 14 normal pregnancies. Erythroblasts with a Y-signal were found as early as 9 weeks of gestation, but at 6 weeks the Y-signal was seen in BPG-negative cells only. These cells showed an epithelioid morphology indicating that they were cytotrophoblasts. The BPG-ISH method provides a simple technique for identifying erythroblasts and simultaneously visualizing a desired probe. PMID- 7784368 TI - Oligohydramnios with amnio-chorionic separation at 15-16 weeks' gestation. AB - Nine patients with oligohydramnios and amnio-chorionic separation were identified out of 7000 women who underwent a vaginal ultrasound examination at 15-16 weeks' gestation. Oligohydramnios was defined as a reduced amount of amniotic fluid, a distance of more than 1 cm between the chorion and amnion, and a good turgor of the amnion without floating membranes of intrauterine sheets. Fetal malformations were observed in all nine cases. In four of six fetuses where chromosomal analysis was available, an abnormal karyotype was found. It is concluded that oligohydramnios in the early second trimester is associated with fetal abnormality. PMID- 7784367 TI - The development of the fetal eye: in utero ultrasonographic measurements of the vitreous and lens. AB - Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective cross-sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r2 = 0.79) and lens (r2 = 0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos. PMID- 7784369 TI - Collagen biosynthesis in cell culture from chorionic villi. AB - After chorionic villus biopsy of human placenta, cell cultures were propagated with Ham's F10 medium or Eagle's minimum essential medium (MEM). It was possible to study the morphology of the cells by transmission electron microscopy (TEM) after a special culture of the cells in a collagen gel. The cells embedded in a collagen gel were able to contract the gel and to organize collagen fibres, as fibroblast cultures do. TEM showed vacuolization and well-developed cisternae of the endoplasmic reticulum, especially in the case of MEM culture. The aim was to determine whether cells cultivated from early placenta were able to synthesize enough collagen for a metabolic study. A high level of collagen biosynthesis could be quantified. Types I and III collagen can be determined which is useful for studying the abnormalities of collagen synthesis in suspected cases of osteogenesis imperfecta or Ehlers-Danlos type IV syndrome. The hydroxylation of lysine can also be studied with respect to Ehlers-Danlos type VI syndrome. Moreover, these cells, in contrast to fibroblast cultures, made it possible to study the biosynthesis of type IV collagen. PMID- 7784370 TI - Early second-trimester diagnosis of sirenomelia. AB - Two cases of sirenomelia are described, detected in the 14th and 16th weeks of gestation by transvaginal ultrasonography. A hypothesis for the aetiology of sirenomelia and its associated anomalies is discussed. PMID- 7784371 TI - Prenatal diagnosis of Freeman-Sheldon syndrome (whistling face). AB - The diagnosis of Freeman-Sheldon syndrome was made by ultrasonographic evaluation of a 20-week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth. PMID- 7784372 TI - Echocardiographic diagnosis of fetal Marfan syndrome at 34 weeks' gestation. AB - Fetal echocardiography was performed during the third trimester in a normal primigravida. The fetal heart was severely affected with the typical cardiac manifestations of Marfan syndrome. The medical history of the father was investigated and a mild form of the syndrome was diagnosed. The neonate died at 2 months of age of congestive heart failure. PMID- 7784373 TI - Early prenatal diagnosis of an infratentorial arachnoid cyst: association with an unbalanced translocation. AB - Arachnoid cysts are an uncommon central nervous system malformation, representing only 1 per cent of all intracranial masses. We report the second-trimester prenatal diagnosis of a posterior fossa arachnoid cyst, associated with an unbalanced X;9 translocation. PMID- 7784374 TI - Digeorge syndrome with total monosomy 22 diagnosed prenatally. AB - A case of monosomy 22 diagnosed prenatally is reported. During pregnancy, ultrasonic observations already revealed several cardiac malformations of the fetus in the 25th week. Following counselling, the pregnancy was terminated. Fetal autopsy revealed several abnormalities associated with DiGeorge syndrome. PMID- 7784375 TI - Fetal cholecystomegaly: a prenatal marker of aneuploidy. AB - The fetal gall bladder can now be easily identified during the second and third trimesters using high-resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19-31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one women underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered. PMID- 7784376 TI - Possibility of screening for fetal hyperinsulinism at genetic amniocentesis in women of advanced maternal age. PMID- 7784377 TI - An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). AB - The incidence of haemangiomas was ascertained by questionnaire in infants born to 578 consecutive CVS patients and 445 consecutive mid-trimester amniocentesis patients seen at a single institution between 1 January 1989 and 31 May 1991. The incidence of 7.4 per cent reported in the amniocentesis group was comparable to previous estimates of the incidence of haemangiomas in the general population. In contrast, a 21.1 per cent incidence, three-fold higher than that observed in the amniocentesis group, was observed among CVS-exposed infants (P < 0.001). This increased incidence was largely confined to patients undergoing a transcervical procedure. No correlation was observed between the incidence of haemangiomas and gestational age at sampling, sample size, number of sampling attempts, or a history of bleeding following the procedure. PMID- 7784379 TI - Genetic amniocentesis following multifetal pregnancy reduction to twins: assessing the risk. AB - Fifty-three patients who elected to reduce their pregnancies to a twin gestation in our centre are known to have subsequently undergone genetic amniocentesis. Five of these patients lost entire pregnancy following the genetic amniocentesis procedure. This is equivalent to a 9.4 per cent pregnancy loss rate for reduced twin gestations in comparison with an expected loss rate of 2 per cent for non reduced twin gestations. PMID- 7784378 TI - Prenatal sonographic signs of possible fetal genital anomalies. AB - The sonographic markers of female and male external genitalia have been documented in early and late gestation. The aim of the present study was to report our experience of possible sonographic markers of fetal genital anomalies. Sonography was performed with a vaginal probe in early gestation and an abdominal sector scanner in advanced gestation. The following genital anomalies were observed: hypospadias, epispadias, ambiguous genitalia, and testicular feminization or Smith-Lemli-Opitz syndrome. It is therefore concluded that prenatal diagnosis of some genital anomalies is now possible. PMID- 7784381 TI - Prenatal sonographic diagnosis of intracranial haemorrhage: report of a case with a sinusoidal fetal heart rate tracing, and review of the literature. AB - The sinusoidal fetal heart rate pattern has been described in association with severe fetal anaemia, with fetal hypoxaemia, and with the administration of parenteral narcotics. Here, we report a case of decreased fetal movement in which a sinusoidal tracing was recorded. The sonographic diagnosis of a massive fetal intracranial haemorrhage was made. A non-interventive approach was taken and the fetus died soon after in utero. We review 28 previous cases in which the prenatal sonographic diagnosis of fetal intracranial haemorrhage was made, including the underlying maternal and fetal factors and neonatal outcomes. We propose that the sinusoidal tracing in this case was due to the intracranial bleed and suggest that fetal intracranial haemorrhage be considered in the sonographic evaluation of the fetus with a sinusoidal pattern. PMID- 7784380 TI - Serum lipid, apolipoprotein and lipoparticle levels in the human fetus. AB - Blood collected from 62 fetuses aged 20-38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life. PMID- 7784382 TI - Prenatal diagnosis of trisomy 21 using interphase fluorescence in situ hybridization of post-replicated cells with site-specific cosmid and cosmid contig probes. AB - Interphase fluorescence in situ hybridization (FISH) with chromosome 21-specific cosmid clones was used to identify trisomy 21 in cultured and uncultured amniotic cells. Two novel site-specific cosmid clones (regions 21q22 and 21qtel) were compared with a cosmid contig (Zheng et al., 1992). Correct identification of chromosome 21 copy number was made in 65-75 per cent of trisomic cells and in 70 75 per cent of normal disomic cells by using all the tested probes. However, the chromosome 21-specific telomeric probe (cos 17F8) showed the best results due to more intense and clearly visible hybridization. Utilization of a directly fluorophorated telomeric probe using Cy3-dCTP and FluorX-dCTP allows accurate detection of chromosome 21 in a fast 'one-step' FISH procedure on uncultured interphase nuclei. In addition, we compared the efficacy of FISH analysis for the total population of interphase cells and cells in the post-replication (late S, G2) periods of the cell cycle. Selective scoring of cells in the post-replicative period (showing a pair of hybridization signals on each chromatid of the replicated interphase chromosome) increased the number of informative nuclei by up to 95-97 per cent. This approach allows cells with overlapping chromosomes, artificial double hybridization signals on separate chromatids in interphase chromosomes, background hybridization, and polyploid cells to be analysed. Application of directly labelled telomeric cosmid probes and integral analysis of hybridized nuclei in the pre- and post-replication periods of the cell cycle may help to further improve the prenatal detection of trisomy 21. PMID- 7784383 TI - Parental reaction and adaptability to the prenatal diagnosis of fetal defect or genetic disease leading to pregnancy interruption. AB - The objective of the study was to evaluate the psychological reaction of two groups of parents to a pregnancy termination after they had undergone a prenatal diagnostic procedure. The analysis involved interviews with a study group of 76 patients who were at risk of giving birth to a child with a genetic disease or defect and a comparison group of 124 who had a pregnancy termination after a major anomaly had been detected by routine ultrasound and who were not at known risk for a genetic disease. Only patients in the study group had received counselling before the prenatal diagnosis and were aware that the fetus could be affected. The overall reaction of the comparison group was one of shock, denial of fetal abnormality, and guilt over 'abandoning the fetus'. A feeling of guilt was expressed by patients in the comparison group (73 per cent versus 29 per cent) in the period immediately following the interruption. One-third of patients in both groups felt obliged to undergo a therapeutic abortion. More patients in the study group than in the comparison group expressed the need to see a psychiatrist at the time of the study (19 per cent versus 7 per cent) and viewed future pregnancies as a replacement for the lost pregnancy (63 per cent versus 19 per cent). The recommendations of the study focus on information sessions to personnel, nursing support, analgesia during the expulsion period, an atmosphere of respect that should be present at the time that the fetus is viewed, the anticipation of mourning, and the long-term follow-up of the couple to ensure that counselling for future pregnancies and psychological support are provided when needed. PMID- 7784384 TI - Detection of fetal HLA-DQa sequences in maternal blood: a gender-independent technique of fetal cell identification. AB - The objective of this study was to detect fetal HLA-DQa gene sequences in maternal blood. HLA-DQa genotypes of 70 pregnant women and their partners were determined for type A1. We specifically sought couples where the father, but not the mother, had genotype A1. In 12 women, maternal blood samples were flow sorted. Candidate fetal cells were isolated and amplified by using PCR primers specific for a paternal HLA-DQa A1 allele. Fetal HLA-DQa A1 genotype was predicted from sorted cells; amniocytes or cheek swabs were used for confirmation. Six of twelve sorted samples had amplification products indicating the presence of the HLA-DQa A1 allele; 6/12 did not. Prediction of the fetal genotype was 100 per cent correct, as determined by subsequent amplification of amniocytes or cheek swabs. We conclude that paternally inherited uniquely fetal HLA-DQa gene sequences can be identified in maternal blood. This system permits the identification of fetal cells independent of fetal gender, and has the potential for non-invasive prenatal diagnosis of paternally inherited conditions. PMID- 7784385 TI - Prenatal diagnosis of familial ring 21 chromosome. AB - Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX,-21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report. PMID- 7784386 TI - Prenatal diagnosis of mosaic 4p- in a fetus with trisomy 21. AB - Mosaicism for the Wolf-Hirschhorn syndrome, del(4)(p16), is extremely rare and has not been reported in association with a numerical chromosome abnormality. We report the prenatal diagnosis of mosaic del(4)(p16) and non-mosaic trisomy 21 in a 16-week female fetus. The pregnancy ended in spontaneous abortion at 34 weeks secondary to fetal demise. The fetus had features of both 4p- and trisomy 21. PMID- 7784387 TI - Fetal translocation between chromosomes 2, 18, and 21 resolved by fish. AB - An apparently balanced t(2q;21q) translocation was discovered in fetal blood and amniocytes of a 22-week fetus, monitored because of ultrasonographic evidence of a heart disease. FISH (fluorescence in situ hybridization) analysis disclosed a complex translocation between chromosomes 2q, 18q, and 21q, which was inherited from the healthy mother. This observation corroborates the usefulness of molecular cytogenetic techniques in raising the quality of prenatal diagnosis and detecting subtle rearrangements not resolved by standard cytogenetics. PMID- 7784388 TI - Blood transferrin receptor expression in chromosomally abnormal fetuses. AB - In a cross-sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17-32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean = 79.8 per cent, range = 60-98 per cent) and nucleated red cell count (mean = 10.4 x 10(9) per 1, range = 1.0-25.0 x 10(9) per 1) were significantly higher than the appropriate normal mean for gestation (z = 3.92, P < 0.0001 and z = 3.69, P < 0.001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression. PMID- 7784389 TI - 46,XY,dup(10q) in direct CVS preparation and mosaic 48,XXXY,dup(10q) in CVS long term culture and fetal tissue. AB - Chorionic villus sampling (CVS) was performed on a 40-year-old woman at 9 1/2 menstrual weeks because of advanced maternal age. The direct preparation showed 46,XY,dup(10)(q11.2q23.2). CVS long-term culture and fetal tissue revealed a rare additional abnormality: 48,XXXY,dup(10)(q11.2q23.2). This abnormality represented the major cell line (> 85 per cent in 691 cells) in an (XY)/XXY/XXXY/(XXXXY) mosaic (all cell lines presumably bearing the dup(10q); the presence of XY and XXXXY cell lines is uncertain). To our knowledge, this is the first report of trisomy 10q11-q23 and of prenatally detected 48,XXXY in chorionic villi. The mosaic could have resulted from early post-zygotic non-disjunctions in a 46,XY,dup(10q) or 47,XXY,dup(10q) zygote. The results from DNA studies of four polymorphisms, mapped to Xp and Xq, support this theory. The literature on prenatally detected cases with sex chromosome tetrasomy and pentasomy and those with additional autosomal abnormalities is reviewed. The reported case underlines the problem of false-negative findings when only direct CVS preparations are karyotyped. PMID- 7784390 TI - Chromosome abnormality in an isolated choroid plexus cyst. PMID- 7784391 TI - Current awareness in prenatal diagnosis. PMID- 7784392 TI - Acceptability and viscosity of low cost home processed supplementary foods developed for preschool children. AB - Four supplement mixtures using whole wheat, pearl millet, bengal gram, green gram, groundnuts and amaranth leaves were developed employing roasting and malting techniques. Malting used in the formation of the supplements reduced significantly hot paste viscosity of all the four supplements and increased their nutrient density per unit volume. The organoleptic trials conducted on rural mothers revealed that taste, texture, colour, aroma, appearance and overall acceptability of all the four supplements were found to be excellent with mean overall acceptability. Children did not develop any GIT disorders after consuming the products. Trained panelists found all the four supplements acceptable as indicated by a nine point hedonic scale. PMID- 7784393 TI - Formulation and characterization of dry mixes based on dehydrated fresh high lysine corn. AB - Fresh sweet corn pulp from high-lysine corn was dehydrated in a drum-dryer and utilized in the formulation of creamy instant soups. Studied formulas contained 27.5 to 67% dehydrated high-lysine corn pulp. The sensory profiles of the formulas improved with increasing proportion of dehydrated fresh corn pulp. Formula with 27.5% fresh corn pulp was rated lowest by the tasters on the basis of poor appearance, low characteristic fresh corn flavor and low overall impression. Formulas with 60 and 67% corn pulp rated highest in sensory quality and were nutritionally adequate. The PER for these formulas did not differ from casein control diet but nitrogen absorption and nitrogen retention was inferior for the formulas protein as compared to casein. PMID- 7784394 TI - Nutrient content of young cassava leaves and assessment of their acceptance as a green vegetable in Nigeria. AB - Cassava (Manihot esculenta Crantz) leaves contained a high level of crude protein (29.3-32.4% dry weight) compared to a conventional vegetable, Amaranthus (19.6%). Ash was 4.6-6.4% in cassava leaf samples but 13.1% dry weight in Amaranthus. Dietary fibre was very high in all samples (26.9-39% dry weight) while HCN potential was low (5.1-12.6 mg/100 g dry weight). Tannin was the highest in IITA red cassava leaves (29.7 mg/g) and the lowest in Amaranthus vegetable. In vitro digestibility was very low in oven dried samples (15.6-22.7%). Blanching increased protein content (except Amaranthus) and in vitro protein digestibility but decreased ash, minerals, dietary fibre and tannin, while HCN-potential was unchanged. Grinding reduced both HCN-potential and tannin by 84 and 71% respectively while oven drying only reduced the HCN content marginally. Preference studies showed that the highest percentage of respondents (25.3%) preferred Amaranthus vegetable, followed by Celosia (17.5%), Talinum (12.4%), garden egg (11.5%), with cassava leaves as the least (0.5%). Organoleptic evaluation rated cassava leaf soup inferior to Amaranthus in terms of appearance, colour and texture but equal in terms of taste and flavour and overall acceptability. PMID- 7784395 TI - Seed characteristics and nutrient composition of selected beans (Phaseolus vulgaris L.) with different ozone tolerance. AB - Ozone sensitivity, nutritional quality, seed characteristics, and growth habit of beans (Phaseolus vulgaris L.) were evaluated in two separate experiments. In the first experiment the data showed a significant variation among 34 bean accessions for ozone sensitivity following acute exposure of 18-day-old plants to 0.6 microliters/l O3 for 2 hours under environmentally controlled greenhouse conditions. PI-163579, PI-169735, PI-171790, PI-176684, PI-201374, PI-310711, PI 345576, PI-370569, PI-379435, and PI-414831 were identified as tolerant to acute ozone exposures. Protein, oil, starch, sugar, and ash contents in the seed of selected germplasm were determined and no correlation was found between these components and ozone sensitivity. Seed size and growth habit varied considerably among the 34 accessions but were not correlated to ozone sensitivity. In a second experiment, ten accessions, selected from the tolerant ones identified in the first experiment, were subjected to chronic ozone exposure in open-top chambers at 0.04 and 0.08 microliters/l concentrations for 7 hours/day 44 days after transplanting. Based on foliar injury and yield reductions, only PI-370569 and PI 414831 were tolerant to prolonged ozone exposure (0.08 microliters/l). A significant positive correlation (r = 0.83) existed between foliar injury rating from chronic treatments involving 0.04 and 0.08 microliters O3/l and acute exposure (0.6 microliter O3/l/2 hours). The data indicated that acute ozone exposure can be used to initially screen a large number of bean accessions, however, this is an imperfect indicator of ozone sensitivity with chronic exposure. PMID- 7784396 TI - Anti-hypertensive substances in fermented soybean, natto. AB - Natto is a traditional Japanese fermented food made by fermenting boiled soy beans with Bacillus natto. Its contents of inhibitors against the angiotensin converting enzyme (ACE, EC3.4.15.1) were investigated. Relatively strong inhibitory activity (IC50: 0.4 mg/ml, 11.8 inhibition units/g natto) was detected in natto extracts and the inhibitory activity observed in the viscous fraction was more potent than in the bean extract. Two groups of inhibitors in the viscous material, high and low molecular weight inhibitors, were resolved by dialysis test. The inhibitor of high molecular weight was a protein with low IC50 value (0.12 mg/ml). The two types of low molecular weight inhibitors were detected in ethanol extracts (IC50: 0.53 mg/ml and 0.95 mg/ml) and they were found to be stable over a wide range of pH and temperature up to 100 degrees C. They were different in the mode of ACE inhibition. One is competitive, and the other noncompetitive against the hydrolysis of Bz-Gly-His-Leu by ACE. PMID- 7784397 TI - Amaranth seed proteins: effect of defatting on extraction yield and on electrophoretic patterns. AB - Acetone and hexane were used to know the effect of defatting amaranth flour on the extraction yield of protein fractions and on the electrophoretic patterns. It was found that albumins (33%) and globulins (20%) did not present yield changes when using these two solvents, but it was noted that with hexane compared to acetone, prolamins extraction was reduced by half (3.0 to 1.6%) whereas glutelins increased from 26.5 to 30%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of prolamins extracted with acetone and hexane showed one band of low molecular weight (22 KDa) and five bands between 52 to 22 KDa, respectively. No electrophoretic changes were observed in the remaining fractions. PMID- 7784398 TI - The Indian laburnum (Cassia fistula L.) fruit: an analysis of its chemical constituents. AB - The edible fruit tissue of Indian laburnum fruit (Cassia fistula L.), a member of the leguminosae family, was analyzed for certain organic compounds and mineral nutrients. Of the nine macro- and micronutrients studied, K was the most highly concentrated such that 100% of the US Recommended Dietary Allowances (RDA) for adults could be met by the consumption of about 100 g of the fresh fruit. Na contents in pulp and seeds are relatively low. Ca content at 827 mg per 100 g of dry matter is one of the highest of any fruits, and could contribute towards the RDA requirement of 800 mg of Ca for adults per day. The fruit is a good source of Fe and Mn, and their concentrations are considerably higher than those found in apple, apricot, peach, pear, and orange. Aspartic acid, glutamic acid, and lysine constituted 15.3, 13.0, and 7.8% of the total amino acids respectively in the pulp. In the seeds the same amino acids constituted, 16.6, 19.5, and 6.6%. The relatively high energy content of the fruit at 18 kJ/g could enhance the daily energy requirement of people in need of adequate caloric intake. The results of the present study demonstrate that the Indian laburnum fruit could be a source of some important nutrients and energy for humans. PMID- 7784399 TI - Biosynthesis of ascorbic acid in germinating rapeseed cultivars. AB - Biosynthesis of ascorbic acid in irradiated and unirradiated germinating rapeseed cultivars was studied at ambient room temperature (20-35 degrees C). Appreciable quantities of ascorbic acid (19.8-24.1 mg/100 g) were detected in the seeds and synthesis of this vitamin increased significantly (three fold) with increasing germination time depending upon rapeseed cultivars (p < 0.05). Soaking of seeds in tap water (1:2) for 24 hours resulted in the decrease of the vitamin in each case. Among the radiation treatments (0.05-0.20 kGy), maximum amounts of ascorbic acid were found in 0.10 kGy (342.1 mg/100 g dry weight) and 0.15 kGy (113.8 mg/100 g wet weight) samples after 96 hours of germination. An overall significant linear relation (r = 0.96) was observed between vitamin biosynthesis and germination time upto 96 hours in rapeseed. PMID- 7784400 TI - Use of peanut and cowpea in wheat-based products containing composite flours. AB - Cowpeas and peanuts are legumes of major dietary and economic importance. They are favored worldwide because of their palatability, contribution to nutritional status, and low cost as a protein source compared to animal protein. Flours processed from cowpeas and peanuts have unique physico-chemical and sensory properties when used in composite flour mixtures. Appropriate blends of cowpea and peanut flours to replace wheat flour in Chinese-type noodles, muffins, and tortillas were determined using modelling and optimization procedures. For noodles, 15% peanut flour and 8% cowpea flour supplementation produced an acceptable product with high protein content (21%). For wheat flour replacement in muffins, up to 43% cowpea and up to 44% peanut flours may be used. However, when wheat flour replacement is 50% or greater, cassava flour should comprise 56 to 72% of the blend with a few exceptions. In tortillas, 24% cowpea and 46% peanut flours produced products similar in quality characteristics to those made from 100% wheat flour. The systematic approach used in these studies is more efficient than the traditional substitution method to optimize sensory qualities of wheat-based products containing composite flours. PMID- 7784401 TI - [Antral gastritis in chronic alcoholism. Role of cirrhosis and Helicobacter pylori]. AB - OBJECTIVES: Antral gastritis is frequent in alcoholics. The role of H. pylori in the pathogenesis of gastritis in these patients is not well known. The aim of our study was to study the role of H. pylori and cirrhosis in the pathogenesis of antral gastritis in alcoholic patients. METHODS: Seventy-nine patients were included in the study. All underwent upper gastrointestinal tract endoscopy with antral biopsies, independently of the presence of abdominal pain, and had serological examination for H. pylori antibodies. RESULTS: Cirrhosis and gastritis were present in 50 and 40 patients respectively, H. pylori serological assay and histological identification of the bacterium were positive in 35 (44%) and 19 (24%) patients respectively. Discrepancy between the 2 tests were observed more frequently in cirrhotic patients. A positive serology with a negative histologic examination for H. pylori was present for 18 cirrhotic and 4 noncirrhotic patients (p < 0.05). A gastritis without evidence of H. pylori was more frequent in cirrhotic than in noncirrhotic patients. H. pylori was histologically present in 11 of 29 cirrhotic patients and in 8 of the 11 noncirrhotic patients with a gastritis (p < 0.05). CONCLUSIONS: Discrepancies between histological examination and H. pylori serology in patients with cirrhosis might be due to the inhospitable environment for H. pylori in case of portal hypertension; the positive serology could be in relation with a past infection. PMID- 7784402 TI - [Evolution of levels of free thyroxine and thyrotropin in treated Cushing disease]. AB - OBJECTIVE: Determine the frequency and changes in thyroid hormones in Cushing's disease. METHODS: Free thyroxin and thyrotropin levels were measured in 11 patients (age range 17 to 60 years) with Cushing's disease both before and after resection of the pituitary adenoma. RESULTS: Free thyroxin levels were low (8.3 to 11.7 pmol/l) in 7 patients. These patients had no clinical manifestations of hypothyroidism. In 4 patients, cure of the pituitary adenoma led to normalization of the thyroid hormones 10 days after operation (13 to 55 pmol/l); in the other cases surgical cure was unsuccessful and thyroxin levels remained low. Cortisol levels were finally normalized in these patients after irradiation of the pituitary, a second pituitary operation, or bilateral resection of the adrenal glands in 2 patients. Normal thyroxin levels were thus achieved. There was no correlation between serum cortisol and free thyroxin. CONCLUSION: Thyroid hormones should be assayed regularly in patients with Cushing's disease as a supplementary control of treatment effectiveness. PMID- 7784403 TI - [Pneumopathies caused by Streptococcus pneumoniae in 27 HIV infected patients]. AB - OBJECTIVES: Determine the clinical features and outcome of acute pneumonia due to Streptococcus pneumoniae in HIV infected patients compared with non-HIV infected patients. METHODS: From January 1986 to February 1992, we observed 33 episodes of pneumococcal pneumonia in 27 HIV-infected patients. Most of the patients were drug addicts (16/27), and/or originated from Central Africa or Haiti (10/27). In 9/27 (33%) patients, HIV infection was previously unknown. Eleven of the 27 patients were at the CDC stages II-III and CD4 cell count was greater than 200/mm3 and CD8 cell count was greater than 1000/mm3 in 12/23 patients and 10/20 patients respectively. RESULTS: In 10/33 episodes, respiratory symptoms were severe: bilateral pneumonia (n = 2) and/or hypoxaemia (n = 9). In 22/33 episodes, hospitalization occurred less than 24 h after the onset of symptoms and in 9/33 episodes, the initial chest X-ray was normal. Streptococcus pneumoniae was isolated in 16/33 episodes, from blood (n = 10), bronchoalveolar lavage (n = 3) or sputum (n = 3). Penicillin G or amoxicillin was used and allowed a favorable and quick response in all episodes. Recurrence occurred in 5/18 (27%) followed patients. These recurrences were not favoured by a low CD4 cell count since it was more than 200/mm3 in these five patients. However, the mean count of CD8 cells was higher in patients with recurrence than in patients without recurrence, 1990/mm3 versus 995/mm3 (p = 0.03). CONCLUSION: CD8 hyperlymphocytosis could increase the risk of recurrence and would help identify a subgroup with higher risk of pneumococcal pneumonia among HIV infected persons. PMID- 7784404 TI - [Idiopathic massive osteolysis of the femur. Syndrome called Gorham-Stout syndrome]. AB - A case of massive osteolysis (disappearing bone disease, phantom bone, Gorham's massive osteolysis) was observed in a young african man with two lesions of the femur. This is a very rare syndrome characterized by an acute spontaneous resorption of bone, without any sign of malignant or infectious disorder. The lesion may develop in any part of the skeleton, with extensive bone loss, but is benign. Bone is replaced by haemangiomatous tissue. The diagnosis lead on the association of clinical, radiological and histological signs. The pathogenesis is still unknown and the treatment remains controversial. Osteolysis stops after a few years, but this is unpredictable; in our case, we have proposed prosthetic replacement, associated with bone grafting and irradiation. PMID- 7784405 TI - [Relationship between type III intestinal metaplasia, age and gastric cancer. 560 biopsies]. AB - OBJECTIVE: A significant association between type III intestinal metaplasia and gastric adenocarcinoma has been demonstrated in gastrectomy and biopsy series. We investigated the effect of age in a large series of gastric biopsies in order to determine whether this association is age dependent or independent. METHODS: Histochemistry examinations were performed in 560 gastric biopsies showing intestinal metaplasia. The percentage of type III versus type I/II metaplasia in patients with malignant (n = 41) or benign disease (n = 519) was compared between patients aged 50 to 69 years and patients aged 70 to 89 years. RESULTS: The prevalence of type III metaplasia increased with age both in malignant (30 vs 61% in the 50-69 and 70-89 year age groups respectively) and benign disease (9 vs 17% respectively). In patients with cancer, type III metaplasia was found more often than type I/II metaplasia (n = 22 vs 19). In the 70-89 year age group, there was a significant difference (p < 0.001) in the percentage of type III metaplasia in patients with cancer (61%) and those with benign disease (17%). CONCLUSION: These findings demonstrate that there is a specific age-independent relationship between intestinal metaplasia and gastric cancer. PMID- 7784407 TI - [Methods for the measurement of insulin resistance. Hyperinsulinemic euglycemic clamp]. AB - Insulin resistance is defined as the decrease of the biological action of insulin, and it mainly presents as an hyperinsulinaemia. The clinical investigation of the states of insulin resistance requires expertise in sophisticated in vivo and in vitro methods. The hyperinsulinaemic euglycemic clamp is the reference method for quantifying insulin resistance. The clamp technique consists in infusing insulin at constant rate and, to prevent any decrease in the plasma glucose level, by infusing dextrose. The rate of dextrose infused to maintain euglycaemia is an estimate of the amount of glucose which is taken up by the tissues under the effect of a defined plasma insulin concentration. Using several rates of insulin infusion allows to establish the relationship between the whole body glucose disposal and plasma insulin levels, and to discriminate between the states of decreased insulin sensitivity and/or altered maximal capacity to dispose of glucose. The measurement of glucose fluxes, using the constant infusion of stable isotope labelled glucose, allows to differentiate the hepatic and the peripheral components of insulin resistance. Insulin sensitivity may be estimated using other methods, such as the minimal model which consists in a mathematical analysis of the intravenous glucose tolerance test. In vitro studies include the search for anti-insulin antibodies and anti-insulin-receptor antibodies, the study of insulin receptors (insulin binding, tyrosine-kinase activity and gene structure) and of the post-receptor glucose metabolism. Genetic syndromes of extreme insulin resistance, the pathophysiology of which is poorly known, are the main applications of these investigations. However, insulin resistance plays an important role in non insulin-dependent diabetes mellitus, and also in insulin-dependent diabetes and various pathological or physiological endocrine disorders. PMID- 7784406 TI - [Farnesyl transferase inhibitors (anti-Ras). A new class of anticancer agents]. AB - Ras genes are frequently activated in human tumours. The role of their product, the P21 proteins, in the transduction of the mitogenic signal makes them attractive targets for an anti-neoplastic therapy. The p21 ras proteins are linked to the plasma membrane and transformed into an active form for signal transmission. Their effect is to mediate the effects of growth factors. Two drug families, the Benzodiazepine peptidomimetics and the CAAX tetrapeptides which inhibit the farnesylation of P21-Ras proteins abolish the transforming properties of mutated P21. These promising drugs could rapidly have clinical applications. They have been shown to be highly active at precise concentrations on ras transformed cells but at the same concentrations are not toxic for untransformed cells. They do not effect other similar enzyme systems within the cell, underlining their selective capacity. Theoretically anti-ras therapy could only suspend cell transformation although it might be possible that if given long enough, a lethal threshold could be reached. PMID- 7784408 TI - [Amyotrophic neuralgia, a multiple atypical form. Possible role of herpes simplex virus]. PMID- 7784409 TI - [Tumor of Oddi's sphincter associated with pemphigus]. PMID- 7784410 TI - [Acute appendicitis in newborn infants. Value of repeated clinical examinations and directed ultrasonography]. PMID- 7784411 TI - [Acute hyponatremia after resection of a pituitary micro-adenoma by transphenoidal approach]. PMID- 7784412 TI - [Critical serum concentration of antibiotics. A therapeutic tool and means of comparative evaluation]. AB - It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data. Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available. The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain. When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue. The relevance of this therapeutic tool in comparison with other methods is discussed. PMID- 7784413 TI - [Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study]. AB - OBJECTIVES: Cabergoline is a new, long-acting D2 agonist, highly effective in suppressing prolactin and restoring gonadal function in hyperprolactinaemic amenorrhoea. This study compares its efficacity and safety with that of the reference compound, bromocriptine. METHODS: A prospective study involved 21 French Centres and 120 women, with hyperprolactinaemic amenorrhoea, randomized to either cabergoline (CAB 0.5-1 mg twice weekly) or bromocriptine (BRC 2.5-5 mg twice daily). Treatment is given under double-blind conditions for the first 8 weeks, and subsequently in open conditions in further 16 weeks with dose adjustments according to response. Patients were assessed for biochemical and clinical efficacy and drug safety (adverse symptoms and biology). RESULTS: Normoprolactinaemia was achieved in 56/60 (93.3%) taking CAB and 27/58 (48.2%) taking BRC (p < 0.0001). Ovulatory cycles or pregnancy were recorded in 71.6% and 48.2% of patients (p = 0.001). Prolactin suppression to below 50% of the baseline value was observed in 1.6% and 15.5% (p = 0.007). Adverse symptoms were recorded in 31/60 (51.6%) and 40/58 (69.2%) patients respectively in the double-blind period, and 53.3% versus 65.5% for the full course of the study. There were significantly fewer gastro-intestinal symptoms in the CAB group, 36.6% versus 84.5% (p < 0.0001). CONCLUSION: Cabergoline is a new prolactin-lowering drug, more effective and better tolerated with fewer gastrointestinal symptoms than the reference compound, bromocriptine. PMID- 7784414 TI - [Directional velocity of the arterial flow, systemic vascular resistance and urinary excretion of sodium in cirrhotic patients]. AB - OBJECTIVES: We have studied the vascular resistance at the posterior tibial artery utilizing the Doppler reverse/forward flow ratio, and its relationship to systemic vascular resistance and renal function in 32 nonazotemic cirrhotic patients. METHODS: Patients were divided into three groups. Group A comprised 10 patients without ascites or oedema; group B comprised 9 patients with ascites and a relatively high sodium excretion (40 +/- 34 mmol/day); and group C comprised 13 patients with ascites and very low sodium excretion (4.9 +/- 2 mmol/day). RESULTS: No significant differences were found in urine flow, creatinine or creatinine clearance between the three groups. Renin and aldosterone levels were found increased in group C. Systemic vascular resistance differed significantly in the three groups, being lower in group C. Significant higher values in the Doppler reverse/forward ratio were observed in patients with markedly increased sodium retention and less systemic vascular resistance (group C). The Doppler reverse/forward ratio showed significant correlations with systemic vascular resistance (r = 0.65; n = 32; p < 0.001), urinary sodium excretion (r = 0.53; n = 32; p < 0.01), renin (r = 0.474; n = 32; p < 0.01) and aldosterone levels (r = 0.589; n = 32; p < 0.001). CONCLUSIONS: These preliminary results suggest in patients with hepatic cirrhosis vascular resistance, assessed non-invasively, at the posterior tibial artery, increases with the severity of sodium retention and the impairment in systemic hemodynamics. Thus, this measurement may be useful for the evaluation and follow-up of patients with cirrhosis of the liver. PMID- 7784415 TI - [Cardiovascular effects of a calcium channel blocker in hypoxia caused by altitude]. AB - OBJECTIVE: High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers. Moreover, calcium entering in the cells could explain the congestive phenomena of acute mountain sickness (AMS). These findings led us to study the action of a calcium channel blocker, isradipine, in the prevention of non-complicated AMS. METHODS: In a double blind randomized study, 20 healthy volunteers received 5 mg of isradipine (n = 6) or placebo (n = 6) for 8 days. After 5 days of treatment in normoxia, the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score, haemodynamic parameters and renal function. RESULTS: The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia. Heart rate was an average of 15 b/min lower in the isradipine group, probably because of a direct action of isradipine on the sinus node. Otherwise, the effects of hypoxia were similar in both groups and were in accordance with the literature. There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to standing position. Renal blood flow, measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia. Cerebral blood flow was elevated, due to the direct vasodilator effect of hypoxia. However this increase did not seem to be the main mechanism responsible for the congestive phenomena. On the other hand, the increase in capillary permeability (demonstrated by the increased transcapillary escape rate of albumin, and albuminuria) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema. Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema. PMID- 7784416 TI - [Detection of the Arg 3500-->Gln mutation of B apolipoprotein. Value in clinical practice]. AB - OBJECTIVE: Familial defective apolipoprotein B-100, caused by a mutation in position 3500 of apolipoprotein B, induces hypercholesterolaemia, a major risk factor of coronary artery disease. The objective is to evaluate the interest of the detecting subjects bearing the Arg3500-->Gln mutation and to observe the response of these subjects to different physiological and therapeutic situations, in clinical practice. METHODS: We performed a systematic screening among hypercholesterolaemic outpatients attending a lipid clinic. The heterozygote subjects were followed up during more than one year and, in some of them, we compared the efficiency of cholesterol-lowering drugs belonging to the different classes: fibrate and statine. RESULTS: Two probands and 3 related subjects were detected. Three patients were treated. For two patients, reduction of LDL cholesterol plasma levels was observed with both drugs but was significantly higher with statine than with fibrate. For the third one, carrying the E2E4 phenotype, the statine did not seemed to have a major effect. CONCLUSION: The number of probands is in agreement with the frequency reported in literature. A possible interaction of the effect of statine with the apo E2 isoform is discussed. PMID- 7784417 TI - [Microfibroendoscopy of the eustachian tube]. AB - The development of extremely minute high performance optical fibers have made possible fibroscopic examination of the Eustachian tube. We have developed a microfibroendoscopic technique since 1987 to explore the Eustachian tube and the tympanic cavity without opening the tympanic membrane. This technique has been used in 125 patients with chronic otitis. The exploration is performed in the operating theatre during a tympanoplasty procedure. Patients are placed in supine position under general anaesthesia. Endoscopic exploration of the Eustachian tube has demonstrated that tube obstruction is very rare, encountered in only 2% of our cases. The major advantage of the technique is the direct antero-posterior visualization of the middle ear. Viewing the middle ear from this anterior view point, the surgeon can analyze regions unattainable with other techniques. The future challenge for this technique is to achieve the goal of non-invasive surgery of the middle ear. PMID- 7784418 TI - [RU 486: current and potential indications. Great expectations and strong resistance]. AB - RU 486 is the code name for mifepristone, a 19-norsteroid first synthesized in 1980. Its chemical structure is similar to progesterone and progesterone derivatives. The difference lies in an 11 beta ring substitution which results in high affinity for progesterone and cortisol receptors. Once linked to the receptor, RU 486 temporarily blocks the action of the corresponding hormone. In vitro and in vivo, RU 486 has a powerful anti-progesterone and anti glucocorticoid effect and a less powerful but nevertheless important anti androgen effect. The essential clinical application for RU 486 involves its anti progesterone effect, currently used in several indications including voluntary pregnancy termination and preparation for the prostaglandin action used to induce labour in interrupted pregnancies. Potential indications have been suggested for preparing the cervix for endo-uterine manoeuvres, induction of labour in term pregnancy and contraception. Other potential indications in gynaecology include breast cancer, endometriosis and uterine fibroma. Meningioma and Cushing's syndrome would be further indications. How far will we go with RU 486? All will depend on the social and economic resistance to the drug and to an even greater extent on ethical considerations. The strength of the anti-RU 486 lobby may well dampen the development of non-contraception indications for this effective anti progesterone agent. PMID- 7784419 TI - [Medical treatment of atrial fibrillation in the healthy heart]. AB - Whatever the cause and clinical features, establishing the strategy for the medical treatment of atrial fibrillation, requires three basic steps. First sinus rhythm must be restored, followed by the prescription of antiarrhythmic drugs to prevent recurrence and finally the use of anticoagulants. Obviously the underlying heart disease has a major effect on the patient's tolerance of atrial fibrillation, the risks of peripheral embolism and overall mortality. In patients with "solitary atrial fibrillation" and an apparently normal heart, each step of the treatment must be examined in light of the individual patients clinical situation and the risks of haemorrhage with anticoagulants as well as the risk of lethal ventricular arrhythmia due to the arrhythmogenic effect of class la or 1c antiarrhythmic drugs. PMID- 7784420 TI - [Uveitis and rifabutin: two new cases]. PMID- 7784421 TI - [Apropos of the resistance to activated protein-C in venous thromboembolic accidents]. PMID- 7784422 TI - [Diaphragmatic paralysis during hereditary myasthenia]. PMID- 7784423 TI - Funnels, pathways, and the energy landscape of protein folding: a synthesis. AB - The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences. This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two-state first-order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uniexponential vs. multiexponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions. PMID- 7784424 TI - Computational approaches to study protein unfolding: hen egg white lysozyme as a case study. AB - Four methods are compared to drive the unfolding of a protein: (1) high temperature (T-run), (2) high pressure (P-run), (3) by imposing a gradual increase in the mean radius of the protein using a penalty function added to the physical interaction function (F-run, radial force driven unfolding), and (4) by weak coupling of the difference between the temperature of the radially outward moving atoms and the radially inward moving atoms to an external temperature bath (K-run, kinetic energy driven unfolding). The characteristic features of the four unfolding pathways are analyzed in order to detect distortions due to the size or the type of the applied perturbation, as well as the features that are common to all of them. Hen egg white lysozyme is used as a test system. The simulations are analyzed and compared to experimental data like 1H-NMR amide proton exchange folding competition, heat capacity, and compressibility measurements. PMID- 7784425 TI - Modeling the quinone-B binding site of the photosystem-II reaction center using notions of complementarity and contact-surface between atoms. AB - Functional identity and significant similarities in cofactors and sequence exist between the L and M reaction center proteins of the photosynthetic bacteria and the D1 and D2 photosystem-II reaction center proteins of cyanobacteria, algae, and plants. A model of the quinone (QB) binding site of the D1 protein is presented based upon the resolved structure of the QB binding pocket of the L subunit, and introducing novel quantitative notions of complementarity and contact surface between atoms. This model, built without using traditional methods of molecular mechanics and restricted to residues in direct contact with QB, accounts for the experimentally derived functional state of mutants of the D1 protein in the region of QB. It predicts the binding of both the classical and phenol-type PSII herbicides and rationalizes the relative levels of tolerance of mutant phenotypes. PMID- 7784427 TI - Dramatic differences in the motions of the mouth of open and closed cytochrome P450BM-3 by molecular dynamics simulations. AB - Molecular dynamics trajectories were calculated separately for each of the two molecules in the asymmetric unit of the crystal structure of the hemoprotein domain of cytochrome P450BM-3. Each simulation was 200 ps in length and included a 10 A layer of explicit solvent. The simulated time-average structure of each P450BM-3 molecule is closer to its crystal structure than the two molecular dynamics time-averaged structures are to each other. In the crystal structure, molecule 2 has a more accessible substrate binding pocket than molecule 1, and this difference is maintained throughout the simulations presented here. In particular, the substrate docking regions of molecule 1 and molecule 2 diverge in the solution state simulations. The mouth of the substrate binding pocket is significantly more mobile in the simulation of molecule 2 than in the simulation of molecule 1. For molecule 1, the width of the mouth is only slightly larger than its X-ray value of 8.7 A and undergoes fluctuations of about 1 A. However, in molecule 2, the mouth of the substrate binding pocket is dramatically more open in the time-average molecular dynamics structure (14.7 A) than in the X-ray structure (10.9 A). Furthermore, this region of the protein undergoes large amplitude motions during the trajectory that are not seen in the trajectory of molecule 1, repeatedly opening and closing up to 7 A. Presumably, the binding of different substrates will induce the mouth region to adopt different conformations from within the wide range of structures that are accessible. PMID- 7784426 TI - A model for the LexA repressor DNA complex. AB - A structural model for the interaction of the LexA repressor DNA binding domain (DBD) with operator DNA is derived by means of Monte Carlo docking. Protein-DNA complexes were generated by docking the LexA repressor DBD NMR solution structure onto both rigid and bent B-DNA structures while giving energy bonuses for contacts in agreement with experimental data. In the resulting complexes, helix III of the LexA repressor DBD is located in the major groove of the DNA and residues Asn-41, Glu-44, and Glu-45 form specific hydrogen bonds with bases of the CTGT DNA sequence. Ser-39, Ala-42, and Asn-41 are involved in a hydrophobic interaction with the methyl group of the first thymine base. Residues in the loop region connecting the two beta-sheet strands are involved in nonspecific contacts near the dyad axis of the operator. The contacts observed in the docked complexes cover the entire consensus CTGT half-site DNA operator, thus explaining the specificity of the LexA repressor for such sequences. In addition, a large number of nonspecific interactions between protein and DNA is observed. The agreement between the derived model for the LexA repressor DBD/DNA complex and experimental biochemical results is discussed. PMID- 7784429 TI - Packing constraints of hydrophobic side chains in (alpha/beta)8 barrels. AB - An analysis of possible tight packing of hydrophobic groups simultaneously at the both surfaces of beta-hyperboloid-8 was conducted. This analysis shows that the disposition of amino acid side chains at the real beta-structure's surface is unique. If we sign the mean distance between adjacent beta-strands as "a," and the mean distance along beta-strand between C alpha atoms, whose side chains are directed to one side of the beta-sheet, as "b," the ratio b/a = square root of 2 very precisely. This ratio ensures the most efficient packing of side hydrophobic groups at the outer surface of beta-hyperboloid-8, forming, at the same time, the second by efficiency packing at its inner surface. PMID- 7784428 TI - The first solvation shell of magnesium ion in a model protein environment with formate, water, and X-NH3, H2S, imidazole, formaldehyde, and chloride as ligands: an Ab initio study. AB - The first coordination shell of an Mg(II) ion in a model protein environment is studied. Complexes containing a model carboxylate, an Mg(II) ion, various ligands (NH3, H2S, imidazole, and formaldehyde) and water of hydration about the divalent metal ion were geometry optimized. We find that for complexes with the same coordination number, the unidentate carboxylate-Mg(II) ion is greater than 10 kcal mol-1 more stable than the bidentate orientation. Imidazole was found to be the most stable ligand, followed in order by NH3, formaldehyde, H2O, and H2S. PMID- 7784430 TI - Preliminary X-ray diffraction analysis of crystals of tomato aspermy virus (TAV). AB - Tomato aspermy virus (TAV) is a member of the T = 3 cucumovirus group, and the chrysanthemum strain (C-TAV) has been crystallized in a form suitable for X-ray structural analysis. The crystals, which grow in 14-17% ethanol at pH 8.5, are of orthorhombic space group I222 with unit cell dimensions of a = 295.1 A, b = 320.5 A, and c = 383.6 A. There are two T = 3 virus particles in the unit cell, which means that they must be centered at 0,0,0 and 1/2, 1/2, 1/2 with icosahedral 222 symmetry elements coincident with crystallographic symmetry operators. The asymmetric unit of the crystals, therefore, contains one quarter of a virus particle, or 45 capsid subunits. Native diffraction data to 4 A resolution have been collected using synchrotron radiation, though data appear to be present beyond that resolution. PMID- 7784431 TI - Purification, crystallization, and preliminary X-ray diffraction analysis of even skipped homeodomain complexed to DNA. AB - Embryonic development in metazoa, to a significant extent, is directed by genes which contain a conserved sequence motif named the homeobox. This sequence encodes a polypeptide called the homeodomain which has sequence specific DNA binding activity. We report the purification, crystallization, and preliminary diffraction analysis of the Drosophila Even-skipped homeodomain (Eve HD) bound to two different oligonucleotides. Crystals of Eve HD complexed with an AT-rich sequence belong to space group P2(1), a = 34.06, b = 61.61, c = 39.99 Angstrom, beta = 90.0 degrees. These crystals diffract to at least 2.0 Angstrom and both native and derivative data sets have been collected. Crystals of Eve HD complexed with a GC-rich sequence belong to space group P6(3), a = b = 124.52, c = 66.78 Angstrom and diffract to 3.5 Angstrom resolution. A native data set has been collected. PMID- 7784432 TI - Inward rectification of neuronal nicotinic acetylcholine receptors investigated by using the homomeric alpha 7 receptor. AB - The strong inward rectification observed in neuronal nicotinic ACh receptors was examined by using alpha-bungarotoxin sensitive, homomeric alpha 7 neuronal nicotinic ACh receptors derived from chick brain. Receptors were expressed in Xenopus laevis oocytes and functionally assessed by the two electrode voltage clamp technique. Site directed mutagenesis of residues thought to line the putative ion pore revealed that negatively charged glutamate residues located at the inner mouth of the channel are essential for rectification. This finding was confirmed both for the active open state and for receptors mutated to conduct in one of the desensitized states. No outward tail relaxations were observed with voltage jumps to depolarizing potentials, suggesting that rectification was not due to intrinsic gating. For the wild type receptor, intracellular injection of CDTA, a chelating agent having a high affinity for Mg2+, reduced rectification in a dose dependent manner, suggesting that rectification originates, in part, from open channel block by internal free Mg2+. These findings support the hypothesis that charged residues at the inner mouth of the pore influence the Mg2+ affinity of the blocking site. PMID- 7784433 TI - Conformational study of the Thr-Gly repeat in the Drosophila clock protein, PERIOD. AB - Recent results with the Drosophila melanogaster period gene suggest that the apparently conserved repetitive motif (Thr-Gly)n encoded by this gene may play an important role in the temperature compensation of the circadian clock. We have therefore initiated both a theoretical and experimental conformational analysis of (Thr-Gly)n peptides. By using a build-up method, it is clear that the hexapeptide (Thr-Gly)3 represents a 'conformational monomer' and generates a stable type II or type III beta-turn. Circular dichroism and nuclear magnetic resonance spectra of synthetic (Thr-Gly)3 and poly(Thr-Gly) peptides revealed that these peptides exhibit flexible conformations, especially in more polar environments and at higher temperatures. We speculate that this flexibility may illuminate our understanding of both the molecular mechanism of temperature compensation and the systematic geographical distribution within Europe of the Thr-Gly length polymorphism in D. melanogaster. PMID- 7784434 TI - Phenomenal motion seen through artificial intra-ocular lenses. PMID- 7784435 TI - Brain-created visual motion: an illusion? PMID- 7784436 TI - Colour identification and colour constancy are impaired in a patient with incomplete achromatopsia associated with prestriate cortical lesions. AB - We have examined visual functions, including colour vision, in a patient with bilateral cortical lesions involving mainly the fusiform and lingual gyri, areas known to be involved in the central processing of chromatic stimuli. The patient has near normal (6/9) acuity, and his responses to tests of binocular function and spatial vision are normal, as are his discrimination of changes in target speed and surface lightness. He does, however, exhibit minor losses in the upper visual field, mild prosopagnosia and topographical agnosia, all conditions commonly associated with cerebral achromatopsia. Colour matches and spectral response data establish that his cone photoreceptors have normal spectral characteristics and his spectral sensitivity measured against a white background reveals normal postreceptoral chromatic function. The patient's colour discrimination for differences in wavelength, hue or saturation is, however, impaired and his colour naming is significantly disturbed, particularly for blues and greens. We have determined the areas of the chromaticity chart that correspond to his naming categories for surface colours, and show that changes in illuminant cause him to alter the names of surface colours in a manner consistent with the changes in their chromaticities. Other subjects with normal or congenital red-green deficient colour vision make many fewer name changes under changes in illuminant. We conclude that the patient's colour constancy is impaired as a consequence of abnormal central processing of colour vision. PMID- 7784437 TI - Molecular support for vicariance as a source of diversity in rainforest. AB - The origin of high diversity in tropical rainforests is attributed to divergence amongst relatively mesic, late Pleistocene refuges. To test this hypothesis we analysed sequence variation within the mitochondrial DNA of populations of six rainforest-dwelling vertebrate species (one lizard and five birds) in the Wet Tropical rainforests of northeastern Australia. Vicariance among historical refuges was indicated by geographically congruent variation across a historical climatic barrier previously predicted by modelling. Sequence divergence across the barrier varied widely, being highest in species with lowest vagility and greatest restriction to rainforest. A high altitude, rainforest-restricted species was exceptional in lacking mtDNA variation. These data support the suggested role of vicariance in promoting evolutionary diversity in rainforests but also indicate variation in the timing of vicariance events, with most speciation or divergence events occurring well before the late Pleistocene. The relation between the amount of molecular divergence and current ecology suggests a sequence of isolation events, perhaps of increasing severity, occurring between the late Tertiary and the late Pleistocene. PMID- 7784438 TI - The inner ear of the echidna Tachyglossus aculeatus: the vestibular sensory organs. AB - The monotremes, comprising the echidnas and platypus, have more sensory organs in the inner ear than do other mammals. In addition to the organs usually seen in the mammalian inner ear, they have a lagenar macula, a sense organ found in all non-mammalian vertebrates. In the echidna Tachyglossus aculeatus, this macula consists of a narrow sensory strip at the end of the cochlea. All vestibular sensory organs are populated by two types of sensory cells, cylindrical bouton innervated hair cells and more or less regular bottle-shaped calyceal-innervated hair cells. The two types are mixed in all vestibular organs, as in placental mammals, and their arrangement in the maculae in particular is very unlike that in reptiles. The sensory epithelia are very large relative to the size of the animals. The utricular macula contains more sensory cells than found in any other amniote so far examined. PMID- 7784439 TI - Kinematics of eye movement control. AB - In this paper a kinematic description of the restrictions imposed on the eye movements is presented. The restrictions arise from a pattern of nonlinear interactions between desired changes in viewing direction and current eye position. It is shown that various reported relations between eye torsion and viewing direction can be derived by changing only the relative weights of the interactions terms. This descriptive scheme may help to elucidate the control of eye torsion in the brainstem. PMID- 7784440 TI - Control of re-entrant activity in a model of mammalian atrial tissue. AB - We evaluate the feasibility of using resonant drift under feedback driven stimulation to control re-entrant excitation in atrial muscle. We simulate a two dimensional sheet of atrial tissue, where the local kinetics are described by the Earm-Hilgemann-Noble equations for a rabbit atrial cell, and the effects of small amplitude spatially uniform forcing of the whole sheet are computed. Repetitive forcing can induce a drift of a spiral wave in the two-dimensional model, with a drift velocity of up to 10 cm s-1. For a 4 cm x 4 cm atrial surface this resonant drift can move the re-entrant spiral to the inexcitable boundaries, eliminating re-entry in less than 10 s when the amplitude of the repetitive stimulation is 10% that of the single shock defibrillation threshold. PMID- 7784442 TI - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical Information Service. PMID- 7784441 TI - Concordant evolutionary patterns among Indo-West Pacific butterflyfishes. AB - Genetic differences within a 495 base pair section of the mitochondrial cytochrome b gene reveal a striking concordance among species in two monophyletic groups of Indo-west Pacific butterflyfishes. In both species groups, an approximately 2.0% genetic break clearly partitions individuals between the Indian Ocean and Pacific Ocean. However, levels of intra-Pacific mtDNA variation are low, on average less than 1.0%, and fail to cluster by species boundaries defined by colour pattern. Individuals from different species, separated by thousands of kilometers, often possess identical cytochrome b sequences, whereas conspecifics from the same reefs can show up to 1.5% difference. The discrepancy between the mtDNA gene tree and species boundaries may reflect retained ancestral variation or may be the result of hybridization. The strong temporal and phylogenetic concordance between these two independent species groups suggests that genetic differentiation was influenced by common environmental factors. Low levels of within- and between-species genetic differences imply a recent divergence time and suggest a link between speciation within each group and Pleistocene climatic fluctuations. These results paint a turbulent picture of the recent evolutionary history of the Indo-West Pacific. PMID- 7784443 TI - Fate of exogenous arachidonic acid in THP-1 cells: incorporation in cell lipids and conversion to outer N-6 fatty acids. PMID- 7784444 TI - Effects of fatty acids on hepatic gene expression. AB - Polyunsaturated fatty acids (PUFA) have dramatic effects on hepatic lipid metabolism by regulating the transcription of specific genes encoding enzymes involved in glycolysis and lipogenesis. The S14 gene, a putative lipogenic protein, has been used as a model to define the molecular basis of PUFA action on hepatic gene expression. We have shown that PUFA-regulated hepatic transcription factors target cis-regulatory elements located between -220 and -80 bp upstream from the 5' end of the S14 gene. Peroxisomal proliferators (PP) also have dramatic effects on hepatic lipid metabolism through effects on gene expression. The mechanism of PP action is mediated, at least in part, through nuclear receptors, i.e. PP activated receptor (PPAR). We found that the potent PP, i.e. WY14,643, suppressed mRNAS14 and the activity of an S14CAT fusion gene in cultured primary hepatocytes. Preliminary mapping studies showed that WY14,643 cis-regulatory elements were located either within the S14 proximal promoter ( 290 and +19), the S14 TRE (-2900 to -2500) or both regions. Gel shift analysis showed that PPAR did not bind S14 promoter elements. These studies suggest that PUFA- and PP-regulated factors may share common cis-acting elements within the S14 promoter. However, if PUFA control of S14 gene transcription is mediated by PPAR, this mechanism does not involve direct interaction of PPAR with the S14 proximal promoter. PMID- 7784445 TI - Fatty acids and adipose cell differentiation. AB - Fatty acids are important metabolic substrates for adipose tissue. In preadipose cells, fatty acids are also potent inducers of various genes encoding proteins directly involved in fatty acid metabolism. On a longer-term basis, fatty acids induce the terminal differentiation of preadipose to adipose cells. Fatty acids act primarily at a transcriptional level. A member of the steroid/thyroid hormone receptor superfamily has been identified by cDNA cloning from a mouse Ob1771 preadipose cell library. This receptor is likely the fatty acid-activated receptor implicated in the transcriptional effects of fatty acids in adipose cells. Thus fatty acids appear to play a new role as signal transducing molecules which are involved in adipose cell differentiation. PMID- 7784446 TI - Cellular differentiation and dietary regulation of gene expression. AB - The differentiation of 3T3-L1 preadipocytes into adipocytes is one of the few well characterized model systems available to study cellular differentiation in culture. We cloned and determined the genetic organization of two murine stearoyl CoA desaturase genes (SCD1 and SCD2), both of which are transcriptionally activated during preadipocyte differentiation, but are regulated differentially by diet in liver and other tissues. These genes are now being used as a model to study mechanisms of cellular differentiation, tissue-specific gene expression, and dietary regulation of gene expression. It is the objective of this article to provide a brief overview of some of the studies on the regulation of the SCD1 and SCD2 genes during 3T3-L1 preadipocyte differentiation, and also on their differential responses to dietary manipulations in liver tissue. PMID- 7784447 TI - Fatty acids in cell signalling: modulation by lipid binding proteins. AB - Long-chain fatty acids and several of their metabolites have now been shown to be involved as primary or secondary messengers in specific cell signalling pathways. In view of their extremely low aqueous solubility, the extracellular as well as intracellular transport of these compounds is assumed to be facilitated by specific lipid binding proteins, such as cytoplasmic fatty acid-binding protein (FABP). In this paper a survey is given on the biological significance and possible modulatory action of intracellular lipid binding proteins for fatty acid mediated signal transduction pathways. PMID- 7784448 TI - Protein kinase C: cellular target of the second messenger arachidonic acid? PMID- 7784449 TI - Fatty acids: ancestral ligands and modern co-regulators of the steroid hormone receptor cell signalling pathway. AB - Long chain fatty acids derived from endogenous metabolism and/or nutrition are regulators of cell signalling pathways. They can be lipid second messengers of signal transduction systems or modulators and regulators of intracellular signalling pathways such as those involved in the mechanism of action of steroid hormones. Fatty acids have been shown to activate gene transcription under the control of some evolutionarily primitive members of the steroid/thyroid superfamily of receptors. They may represent ancestral ligands of this superfamily of receptors. Fatty acids are also known to regulate the activity of protein kinases, particularly protein kinase C, and thereby phosphorylation of intracellular proteins involved in regulation of gene transcription. Fatty acids may be co-regulators in the cross-talk between membrane-triggered signal transduction and the intracellular steroid hormone signalling pathway. Fatty acids are known to affect either negatively and/or positively the binding of steroid hormones to their specific plasma transport proteins and their specific intracellular receptors and, very recently, fatty acids have also been shown to co-regulate glucocorticoid-dependent gene expression. The mechanism of action of steroid hormones will be used as an illustration of how fatty acids can intervene at different levels of cellular organization to regulate biological activity, with a focus on the glucocorticoid receptor. PMID- 7784450 TI - Specificity and mechanism of fatty acid inhibition of aldosterone secretion. AB - We have shown that unesterified, unsaturated long-chain fatty acids inhibit angiotensin II (AII) binding to receptors in adrenal glomerulosa cells. In this report, we show that oleic and arachidonic acids are specific inhibitors of the AT1 subtype of angiotensin receptor, and exert no effect on receptors of the AT2 subtype. By contrast, decanoic acid is a weak inhibitor of the AT2 subtype only. Our previous work on a post-receptor locus of inhibition by fatty acids of aldosterone biosynthesis showed that the 18-oxidase step is uniquely sensitive. In brief, the first and last steps involved in angiotensin-stimulated aldosterone secretion are particularly sensitive to inhibition by fatty acids. These results suggest a specific role for unesterified fatty acids in regulation of salt and water metabolism. PMID- 7784452 TI - Blood cell redox status and fatty acids. AB - Glutathione-dependent peroxidase (GSH-Px) degrades the deleterious hydroperoxides, including those issued from arachidonic acid (AA) by the action of lipoxygenases, into their alcohol counterpart. We report that the hyperactivity of platelets from elderly people and of polymorphonuclear neutrophils from allergic patients, at least partly due to higher formation of thromboxane A2 and leukotriene B4, respectively, is associated with a depressed GSH-Px activity. As we report that n-3 fatty acids may enhance the cell GSH-Px activity, we conclude that the reduction of cell hyperactivity described in response to those fatty acids might be linked to their effect on GSH-Px. PMID- 7784451 TI - Role of GTP-binding proteins in the polyunsaturated fatty acid stimulated proliferation of mouse mammary epithelial cells. AB - Polyunsaturated fatty acids enhance the proliferation of mouse mammary epithelial cells stimulated by epidermal growth factor (EGF) by modulating the post-receptor signaling pathways. The growth stimulatory effect of these fatty acids is completely inhibited by pertussis toxin, whereas the inhibition of EGF and insulin stimulated growth is only partial. The treatment of cell cultures with 12 O-tetradecanoyl-phorbol-13 acetate (TPA) reverses the growth inhibitory effect of pertussis toxin and fully restores the growth as was in the control cultures untreated with the toxin suggesting a role for PKC in this reversal. It appears that the functions of Gi-proteins are required in the mediation of fatty acid effect on growth. The predominant types of Gi alpha in mammary epithelial cells are Gi alpha 1, Gi alpha 2, and Gi alpha 3. Among these, the levels of Gi alpha 1 and 2 appears to be regulated by steroid hormones. Linoleic acid raises the level of GTP-bound Ras in the cells above the levels induced by EGF. Pertussis toxin reduces the level of Ras-GTP and inhibits phosphorylation of MAP kinase by EGF. It has been speculated that Gi-proteins interact with the receptor bound nucleotide exchange factor and the membrane anchored Raf kinase and constitute two sites for pertussis toxin action. The phosphorylation by PKC may uncouple Gi protein interaction with these effectors and enable the agonist-induced signals to bypass the inhibitory action of PT on growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784454 TI - Structure-activity relationship of the effect of cis-unsaturated fatty acids on heart sarcolemmal phospholipase D activity. AB - This study examined the role of fatty acids on the phosphatidylcholine-specific phospholipase D (PLD) function of purified sarcolemmal (SL) membranes isolated from rat hearts. The enzyme's hydrolytic activity was determined by measuring [14C] phosphatidic acid formation from exogenous [14C] phosphatidylcholine (PtdCho) in the absence or presence of the sodium salts of various saturated or unsaturated long-chain fatty acids (FA). In certain experiments the enzyme was also assayed in the transphosphatidylation mode. Cis-unsaturation and free carboxyl groups were structural prerequisites for the stimulatory effect exerted by FA on SL PLD. The most effective compounds were arachidonate and oleate, which maximally activated PLD at 4 and 5 mM concentration, respectively. To verify if a detergent-like mechanism was involved in PLD activation, anionic, zwitterionic and non-ionic detergents were used. Only anionic taurodeoxycholate had a slight effect, which was about 7% of that achieved by arachidonate or oleate. These results suggest that cis-unsaturated FA activate cardiac sarcolemmal PLD by a mechanism(s) which seems to be unrelated to non-specific perturbation of the membrane. PMID- 7784453 TI - Fatty acyl CoA esters as regulators of cell metabolism. AB - Long chain fatty acyl CoA esters have the ability to interact with certain proteins and thereby serve as effectors in cell metabolism. In particular, they can displace nucleotides from specific nucleotide dependent or binding proteins and interfere with their action. The ADP/ATP carrier and uncoupling protein are two examples where the interplay of nucleotide and acyl CoA binding to the proteins regulate their function. Other proteins such as glucokinase can be considered in this group. In certain tissues like liver they are affected during fasting and insulin deficiency, and when serum fatty acids and liver acyl CoA levels are elevated. More recently, an acyl CoA binding protein in E. coli has been found to be a transcription factor for gene regulation of fatty acid metabolism enzymes. There appears to be some consensus in the amino acid sequence for acyl CoA binding sites on these proteins which serve a variety of important roles in cellular metabolism. PMID- 7784455 TI - Direct effects of fatty acids and other charged lipids on ion channel activity in smooth muscle cells. AB - A variety of fatty acids increase the activity of certain types of K+ channels. This effect is not dependent on the three enzymatic pathways that convert arachidonic acid to various bioactive oxygenated metabolites. One type of K+ channel in toad stomach smooth muscle cell membranes in activated by fatty acids and other single chain lipids which possess both a negatively charged head group and a sufficiently hydrophobic acyl chain. Neutral lipids have no effect on K+ channel activity, while positively charged lipids with a sufficiently hydrophobic acyl chain suppress channel activity. Acyl Coenzyme A's, which do not flip across the bilayer, act only from the cytosolic surface of the membrane, suggesting that the binding site for channel activation is also located there. This fatty acid activated channel is also activated by membrane stretch. Moreover, this mechanical response is either mediated or modulated by fatty acids. Thus, fatty acids and other charged single chain lipids may comprise another class of first or second messenger molecules that target ion channels. PMID- 7784456 TI - Regulation of pituitary-adrenocortical activity by free fatty acids in vivo and in vitro. AB - Virtually every metabolic disorder characterized by elevated plasma free fatty acid (FFA) levels is also associated with hypercorticoidism. For example, the glucocorticoid response to insulin-hypoglycemia is shown in this report to be greatly potentiated in Type I diabetic rats. Since glucocorticoids (corticosterone, in rats) potentiate lipolysis and promote gluconeogenesis, they exacerbate diabetes. We found that elevation of circulating FFA levels in normal rats (via Intralipid/heparin infusion) increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and resulted in hyperglycemia. In vitro, however, cultured pituitary cells were relatively unaffected by FFA except at very high concentrations. Neither basal ACTH secretion nor the ACTH response to corticotropin-releasing hormone (CRH) was affected by pathophysiological molar ratios of FFA:BSA. Thus, the ACTH secretory response to FFA in vivo likely is mediated via neuroendocrine activation. Cultured adrenocortical cells, however, were stimulated by oleic acid and, to a lesser extent, by linoleic acid; saturated fatty acids were without effect. The latencies of oleic acid-induced steroidogenesis in vitro and Intralipid-induced corticosterone secretion in vivo were both about 60 min. We conclude that pathophysiological levels of circulating FFA (typical of diabetes, obesity, starvation, and consumption of high-fat diets) initiate a positive feedback loop between the adipocyte and the HPA axis, which ultimately exacerbates the symptoms of these disorders. PMID- 7784457 TI - Omega-3 fatty acids and prevention of ventricular fibrillation. AB - Interest in the potential cardiovascular benefits of omega-3 long chain polyunsaturated fatty acids has been largely focused on possible antiatherothrombotic effects. In addition, however, definitive antiarrhythmic effects of these dietary omega-3 fatty acids have been reported by Charnock & McLennan. Our studies commenced with the observation that two of these fatty acids, eicosapentaenoic (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) prevented contracture and fibrillation of isolated neonatal cardiac myocytes when exposed to toxic levels of ouabain (0.1 mM). This protection was associated with prevention of excessively high intracellular calcium concentrations in the myocyte. Further, it was shown that these fatty acids modulate calcium currents through L-type calcium channels and that the effect occurs within a few minutes of adding EPA or DHA to the medium perfusing the cultured cardiac myocytes. Infusing an emulsion of the omega-3 fatty acids intravenously just prior to compression of a coronary artery in a conscious, prepared dog will prevent the expected subsequent ischemia-induced ventricular fibrillation. PMID- 7784458 TI - Altered lipid metabolism in the failing heart of cardiomyopathic hamsters (UM X7.1). AB - The lipid composition of different anatomic regions of 150 day-old UM-X7.1 cardiomyopathic hamster and age-matched controls (Syrian golden hamsters) was examined. Cardiomyopathic hamsters exhibit a phospholipid to protein ratio higher than healthy animals in atria, whereas the contrary is true in the other anatomic regions examined. In all tissues the cholesterol to phospholipid ratio is higher in cardiomyopathic hamster than in controls. Healthy and UM-X7.1 hamsters differ substantially as far as the percent distribution of fatty acids in total lipids is concerned, the lipids from cardiomyopathic animals accumulating fatty acids of the omega-6 series and being relatively poor in monoenoic fatty acids. The different fatty acid composition of heart lipids appears to be a consequence of a generalized disturbance of the lipid metabolism in cardiomyopathic hamsters during congestive heart failure. PMID- 7784460 TI - Central obesity and free fatty acid metabolism. PMID- 7784459 TI - Coupling the cholesterol- and tumor-suppressive actions of palm oil to the impact of its minor constituents on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. AB - The impact of palm oil on cardiovascular disease and cancer may be explained by the mevalonate-suppressive action of constituent isoprenoid end products of plant secondary metabolism. Assorted monoterpenes, sesquiterpenes, carotenoids and tocotrienols down regulate, post-transcriptionally, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity thereby modestly decreasing cholesterol synthesis and concomitantly decreasing LDL cholesterol. The reductase activity in tumor tissues differs from that of liver in being resistant to sterol feedback regulation. Tumor reductase activity retains sensitivity to the post transcriptional regulation. As a consequence, the isoprenoid-mediated suppression of mevalonate synthesis depletes tumor tissues of two intermediate products, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are incorporated post-translationally into growth control-associated proteins. PMID- 7784461 TI - Proceedings of the 2nd International Round Table on Fatty Acids in Cell Signaling. Madison, Wisconsin, 12-13 June 1994. PMID- 7784462 TI - The binding of novel phenolic derivatives of anandamide to brain cannabinoid receptors. AB - Arachidonylethanolamide (N-2-hydroxyethyl-arachidonamide) or 'anandamide' is a naturally occurring derivative of arachidonic acid that has been shown to bind and activate cannabinoid receptors in the brain. Since other potent ligands for the cannabinoid receptor have an aromatic hydroxyl group, we investigated the hypothesis that replacement of the ethanolamine hydroxyl with an aromatic hydroxyl will increase the binding affinity for the cannabinoid receptor. Two novel congeners of anandamide containing aromatic hydroxyl groups were synthesized: N-2-(4-hydroxyphenyl)ethyl arachidonamide (HEA) and N-2 hydroxyphenyl arachidonamide (HPA). The affinity of these congeners for the brain cannabinoid receptor was determined by competition with [3H]CP55940. HEA competed for [3H]CP55940 binding with a Ki of 600 nM; HPA had a Ki of 2200 nM. These results indicate that increased size in the amide portion of anandamide decreases affinity for the receptor. Phenylmethylsulfonyl fluoride (PMSF), an inhibitor of anandamide catabolism by brain membranes, had no effect on the binding of either HEA or HPA. We conclude that these congeners are not substrates for the amidase that catabolizes anandamide. PMID- 7784463 TI - Fatty acid ethyl esters: non-oxidative metabolites of ethanol. AB - Fatty acid ethyl esters are esterification products of fatty acids and ethanol. These compounds have been detected in the serum and cells of individuals following ethanol ingestion. Fatty acid ethyl esters can be quantitated by gas chromatography-mass spectroscopy (GC-MS) in the serum following ethanol ingestion and have been found in concentrations up to 42 microM. Fatty acid ethyl esters have also been isolated from adipose tissue of subjects ingesting fatty acid ethyl ester capsules as well as from subjects ingesting ethanol. HepG2 cells, a human hepatoblastoma cell line, have also been shown to generate fatty acid ethyl esters when incubated with 1.25 microM fatty acid and 0.17 M ethanol. Fatty acid ethyl esters were found to be toxic to HepG2 cells when presented to the cells in the core of low density lipoprotein particles. PMID- 7784464 TI - Cellular regulation of arachidonate mobilization and metabolism. AB - Synthesis of eicosanoids is initiated by signal transduction cascades which result in the hydrolysis of free arachidonic acid from membrane phospholipids. Both a cytosolic 85 kDa and a nonpancreatic 14 kDa PLA2 may contribute to cellular arachidonate mobilization. In many cells, agonist-stimulated fatty acid release is dependent upon increases in intracellular free calcium and is enhanced by pretreatment with agents such as phorbol esters and soluble diglycerides. The response is specific for arachidonate and structurally similar polyunsaturated fatty acids containing a cis 5, 6 double bond. DMSO-differentiation of U937 cells markedly enhances the A23187-stimulated release of [3H]arachidonate, which appears to be coupled to differentiation-induced enhancement of capacitance calcium entry. Although both phorbol esters and soluble diglycerides enhance subsequent fMLP or A23187-stimulated arachidonate release in human neutrophils, several lines of evidence indicate that the effects of oleoylacetylglycerol and 1,2-dioctanoylglycerol are protein kinase C-independent. Soluble diglycerides, but not phorbol esters, enhance the coupling of arachidonate mobilization to subsequent leukotriene B4 synthesis. Further studies will be required to elucidate the mechanisms which regulate activation of cellular phospholipases and subsequent synthesis. PMID- 7784466 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 7784465 TI - Differences in the regulation of biosynthesis of 20- versus 22-carbon polyunsaturated fatty acids. PMID- 7784467 TI - Regulation of prostaglandin endoperoxide synthase (cyclooxygenase) isozyme expression. PMID- 7784468 TI - Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. AB - In traditional medicine, Ayurveda, several spices and herbs are held to possess medicinal properties. Earlier we have reported that extracts from several spices, including turmeric, inhibit platelet aggregation and modulate eicosanoid biosynthesis. Due to their eicosanoid-modulating property, it was suggested that the spices may serve to provide clues to drugs directed to arachidonic acid (AA) pathway enzymes as pharmacological targets. Curcumin, a major component of turmeric, inhibited platelet aggregation induced by arachidonate, adrenaline and collagen. This compound inhibited thromboxane B2 (TXB2) production from exogenous [14C] arachidonate in washed platelets with a concomitant increase in the formation of 12-lipoxygenase products. Moreover, curcumin inhibited the incorporation of [14C]AA into platelet phospholipids and inhibited the deacylation of AA-labelled phospholipids (liberation of free AA) on stimulation with calcium ionophore A23187. Curcumin's anti-inflammatory property may, in part, be explained by its effects on eicosanoid biosynthesis. PMID- 7784469 TI - The regulation of arachidonate lipoxygenase metabolite formation in cells derived from intrauterine tissues. AB - Products of arachidonic acid (AA) metabolism via the lipoxygenase pathways may have key roles in the maintenance of pregnancy and the onset of labor. We have determined whether calcium ionophores can modulate the rate of biosynthesis within the uterus of five important arachidonate lipoxygenase metabolites, i.e. leukotriene B4 (LTB4), LTC4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. Amnion, chorion, and decidual cells were isolated, grown to confluence and incubated with ionomycin. The production of LTB4, LTC4, 5-HETE, 12 HETE, and 15-HETE was determined using specific radioimmunoassays. Cell-specific, concentration-related stimulatory actions of ionomycin on 5-HETE, 12-HETE, 15 HETE, and LTC4 but not LTB4 production were found. A23187 had effects similar to ionomycin. Hence elevation of intracellular calcium levels can result in enhanced intrauterine production of arachidonate lipoxygenase metabolites that may affect pregnancy outcome. PMID- 7784470 TI - Prostaglandin metabolism during growth and differentiation of the regenerating vertebrate appendage. AB - House lizards are able to regenerate their tails. This is an ideal model to study the growth and differentiation of an organ. Prostaglandins (PGs) are local hormones having diverse and potent biological activities. In an effort to understand PG metabolism during the growth and differentiation of the regenerating lizard tail, we analysed the fatty acid (FA) composition of phospholipids are free FAs by GC, the activity of two rate-limiting enzymes (phospholipases A and C), the activity of the enzyme responsible for the oxygenation of polyunsaturated fatty acids to PGs (cyclooxygenase) and characterized the endogenous PGs by HPLC. It was observed that on the 20th day, i.e. the tissue differentiation period, there was an increase in phospholipase A activity, together with a sudden fall in the free arachidonic acid (AA) level, an increase in cyclooxygenase activity and the appearance of endogenous PGE2. PGE2 can stimulate cyclic adenosine monophosphate (cAMP) production and it may stimulate a cascade of events associated with tissue differentiation. PMID- 7784471 TI - Angiotensin II stimulates peptide leukotriene production by guinea pig airway via the AT1 receptor pathway. AB - Angiotensin II (Ang II) regulates a variety of physiological functions, including contraction of smooth muscle. Peptide leukotrienes (LTs) have recently been reported to be potent bronchoconstrictors and may play a role in the pathogenesis of airway inflammation. However, the possibility that Ang II and peptide LTs interact in the control of airway function has not been studied. In this study, we showed that Ang II receptors are present on guinea pig airway, and that they are of the AT1 subtype. We showed the possibility that Ang II induced the release of peptide LTs from guinea pig airway by activation of the AT1 receptor pathway. Our findings thus suggest that interaction between Ang II and peptide LTs might increase airway inflammation in the guinea pig. PMID- 7784472 TI - Studies on the mechanism of PAF-induced vasopermeability in rat lungs. AB - The present study evaluated the effect of platelet activating factor (PAF) instilled into rat airways on vascular permeability assessed in isolated lung tissues by Evans blue (EB)-labelled plasma protein extravasation. It was found that intratracheal instillation of PAF induces a dose-dependent increase of EB extravasation in the bronchi (upper and inner) but not in the lung parenchyma. The contribution of eicosanoids to PAF-induced increase of vascular permeability was investigated by treating the animals with selected inhibitors prior to PAF administration. Mepacrine (5 mg/kg), L-663,536 (10 mg/kg), indomethacin (4 mg/kg) and dazoxiben (10 mg/kg) significantly reduced EB extravasation in the bronchi. The PAF antagonists BN-52021 (5 mg/kg), WEB-2086 (1 mg/kg), WEB-2170 (5 mg/kg) and PCA-4248 (3 mg/kg) were all effective in reducing the extravasation. These results suggest that PAF-induced increase of vascular permeability in rat bronchi is mediated by cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. PMID- 7784473 TI - Hypoglycemia stimulates thrombin-induced PGI2 production by cultured human umbilical vein endothelial cells. AB - The effect of a low concentration of glucose on prostacyclin (PGI2) production by human umbilical vein endothelial cells in culture (HUVEC) was examined. When HUVEC were cultured for 24 h in a medium containing various concentrations of glucose (0.26, 0.63, or 1.29 mg/ml), thrombin-induced PGI2 production was increased in the cells exposed to low concentrations of glucose; the increase was inversely proportional to the glucose concentration and was seen at all concentrations of thrombin tested. Thus, hypoglycemia may increase the production of PGI2 by endothelial cells in vivo, leading to a compensatory vasodilation with an increase in blood flow to increase the delivery of glucose. PMID- 7784474 TI - Effects of fatty acyl coenzyme A esters on lipoxygenase and cyclooxygenase metabolism of arachidonic acid in rabbit platelets. AB - The effects of fatty acyl coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl , linoleoyl- and arachidonoyl--CoA) on the activities of lipoxygenase and cyclooxygenase in rabbit platelets were examined. Palmitoyl-, stearoyl-, oleoyl- and linoleoyl- CoA were potent inhibitors of platelet lipoxygenase activity. In addition to the lipoxygenase, the four fatty acyl-CoA esters elicited inhibitory activity on platelet cyclooxygenase, although the inhibition was a little weaker. The CoA derivative of the icosanoid precursor arachidonic acid (AA) showed little inhibition on lipoxygenase and cyclooxygenase. Palmitic, stearic and oleic acids had little or no effect on lipoxygenase and cyclooxygenase, in contrast with their CoA derivatives. Linoleic acid was more potent than linoleoyl-CoA as an inhibitor of the cyclooxygenase, but it was a weak inhibitor of the lipoxygenase. These results suggest that the CoA derivatives of palmitic, stearic, oleic and linoleic acids have the potential to modulate both platelet lipoxygenase and cyclooxygenase activities and may have functional effects within platelets. PMID- 7784475 TI - Eicosapentaenoic acid modulates arachidonic acid metabolism in rat alveolar macrophages. AB - Eicosapentaenoic acid (EPA) is an unsaturated fatty acid contained in fish oils. In order to clarify the mechanism of its anti-inflammatory effects on the lung, we studied arachidonic acid (AA) metabolism by in vitro exposure of rat alveolar macrophages to EPA. EPA was found to inhibit the endogenous production of leukotriene B4 (LTB4) from AA. At a low concentration of EPA, generation of LTB5 was increased, while at a high concentration it was decreased. These results suggest that at a lower concentration EPA may be competitive with AA as a substrate, and that at a higher concentration it may directly inhibit AA metabolism via inhibition of 5-lipoxygenase or phospholipase A2. PMID- 7784476 TI - Enhancement of prostacyclin production in cultured bovine aortic endothelial cells by oxidized glycated low-density lipoprotein. AB - Oxidized low-density lipoprotein (oLDL) is implicated in the pathogenesis of atherosclerosis. The serum concentration of glycated LDL (gLDL) is increased in diabetics, and it is possible that oxidative modification of gLDL contributes to the increased incidence of atherosclerosis associated with diabetes. The mechanism and effect on prostacyclin (PGI2) production by cultured bovine aortic endothelial cells of oxidized glycated LDL (ogLDL) prepared in vitro have now been examined. Glycation of LDL was performed by incubating LDL with 20 mM glucose for 3 days. ogLDL was then prepared by incubation of gLDL with 1 microM CuSO4 for 12 h. Both the electrophoretic mobility and the thiobarbituric acid reactive substance content of ogLDL were greater than those of native LDL (nLDL) or gLDL. Binding, cell-association, and degradation of ogLDL in endothelial cells were significantly greater than those of nLDL and gLDL. The stimulatory effect of ogLDL on PGI2 production was significantly greater than that of nLDL or gLDL; this effect was dose dependent. Both cell-association and the stimulatory effect on PGI2 production of oLDL were dependent on the extent of oxidation in a biphasic manner. Endothelial cells thus appear to protect against atherosclerosis by removing atherogenic lipoproteins and by producing PGI2. PMID- 7784477 TI - Diabetes mellitus-induced alterations of hepatobiliary function. PMID- 7784478 TI - Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system. PMID- 7784479 TI - Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. AB - From pharmacological investigations and clinical studies, it is known that ACE inhibitors exhibit additional local actions that are not related to hemodynamic changes and that cannot be explained only by interference with the renin angiotensin system by means of an inhibition of ANG II formation. Because ACE is identical to kininase II, which inactivates the nonapeptide BK and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. ACE inhibition, concentration, and time dependently increased the formation of NO and PGI2 in cultured endothelial cells of different origin and from different species, including humans. The specific B2 kinin receptor antagonist, icatibant, suppressed the ACE inhibitor-induced increase in endothelial cyclic GMP accumulation index for NO-formation and, in parallel, attenuated the increase in PGI2 release. In renovascular models of hypertension associated with a stimulated renin-angiotensin system (two-kidney, one-clip), blood pressure reduction by ACE inhibitors was attenuated by icatibant, whereas in rats with genetic hypertension with normal to low plasma renin, blood pressure reduction through ACE inhibitors was not affected. In experimental atherosclerosis in rabbits, ACE inhibitors were able to preserve endothelial function and vascular reactivity and to reduce surface involvement. In the balloon denudation model of carotid arteries in rats, it was found that ACE inhibition markedly reduced neointima formation. However, when the ACE inhibitor was given together with icatibant, its effect was significantly blunted. Perfusion with ACE inhibitors induced a reduction of the incidence, as well as of the duration, of ventricular fibrillation and improved cardiodynamics and myocardial metabolism. BK perfusion induced comparable cardioprotective effects. In addition, perfusion with ACE inhibitors markedly increased the outflow of BK and related kinins from isolated rat hearts. The antiischemic effect of ACE inhibitors and BK were abolished by the addition of L-NNA (1 x 10(-6) mol/l) or icatibant (1 x 10(-9) mol/l). Similar results were found in dogs and rabbits with myocardial infarction. BK and related kinins also seem to be involved in preconditioning and remodeling. The effect of ACE inhibition in LVH was investigated in rats made hypertensive by aortic banding. ACE inhibition with ramipril, in the antihypertensive dose of 1 mg/kg/day for 6 weeks, prevented the increase in blood pressure and the development of LVH. A lower, nonantihypertensive dose of the ACE inhibitor (10 micrograms/kg/day for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity, but also prevented LVH after aortic banding.4+ off PMID- 7784480 TI - Transforming growth factor alpha: expression, regulation, and biological activities. PMID- 7784481 TI - Regulation of pulmonary vascular tone. PMID- 7784482 TI - Dr. William James: physician-philosopher (1842-1910). PMID- 7784483 TI - Will there be a job for you? The physician work force under health care reform. PMID- 7784484 TI - From stethoscope to spreadsheet: the physician with an M.B.A. PMID- 7784485 TI - Traditional African medicine. PMID- 7784486 TI - A night at the clinic. PMID- 7784487 TI - Basic lessons in resource allocation: sharing, setting limits, and being fair. PMID- 7784489 TI - Physician education in a diverse society: listening to and learning from new voices. PMID- 7784491 TI - Questions and reflections. Death, where is thy sting? PMID- 7784488 TI - Anthrax: from Mesopotamia to molecular biology. PMID- 7784490 TI - Western and traditional medicine in Africa: a century of encounter. PMID- 7784492 TI - Polish medicine. PMID- 7784493 TI - Tuberculosis in New York City's homeless. PMID- 7784494 TI - In defense of defensive medicine. PMID- 7784495 TI - Encounters with Soma Weiss. PMID- 7784496 TI - Pulmonary circulation and Ibn Nafis. PMID- 7784498 TI - Sixty-eight president of APS. PMID- 7784497 TI - Health care workers, patients, and HIV: an analysis of the policy and ethical debate. PMID- 7784499 TI - The future of academic health centers. PMID- 7784500 TI - O'Doherty receives APS-Genentech Fellowship. PMID- 7784501 TI - Purification, characterization, and cDNA cloning of profilin from Phaseolus vulgaris. AB - Profilin from common bean (Phaseolus vulgaris L.) was purified to homogeneity by poly-L-Pro affinity chromatography and gel filtration. The hypocotyl and symbiotic root nodule protein was detected as a single isoform with a 14.4-kD molecular mass and an isoelectric point of 5.3. Partial amino acid and DNA sequencing of a full-length cDNA clone confirmed its identity as profilin. An antibody generated against the purified protein binds to a protein with the same molecular mass in leaves and nodules. Immunolocalization of the protein showed a diffuse distribution in the cytoplasm of hypocotyls and nodules but enhanced staining at the vascular bundles. The strong identity of the sequence among the profilins of birch, maize, and bean suggests that it may play an important role in the signal transduction mechanism of plant cells and plant-bacterial symbioses. PMID- 7784502 TI - Three glycosylated polypeptides secreted by several embryogenic cell cultures of pine show highly specific serological affinity to antibodies directed against the wheat germin apoprotein monomer. AB - Embryogenic tissues of Pinus caribaea Morelet var hondurensis produce extracellular proteins; among them germins have been identified. Two-dimensional electrophoresis followed by electroblotting onto a polyvinylidene difluoride membrane allowed isolation and N-terminal amino acid sequencing of extracellular GP111, which is present within the five embryogenic cell lines studied. The amino acid sequence showed strong homologies with the sequences of germins deduced from cDNA sequencing, starting at the same amino acid position but one, compared with other sequences of mature germins deduced from protein sequencing. Immunoblots of embryogenic and nonembryogenic extracellular proteins indicated that the polypeptide GP111 plus two others with similar relative molecular mass values are present in embryogenic cell lines but not in nonembryogenic ones. They were recognized by an antiserum raised against the nonglycosylated monomer of wheat germin. The cross-reaction between pine and wheat apoproteins was highly specific. An antiserum against the glycosylated pentameric germin-like protein (an oxalate oxidase) of barley cross-reacted with all three, as well as with several other glycosylated polypeptides. PMID- 7784503 TI - Pathogenesis-related PR-1 proteins are antifungal. Isolation and characterization of three 14-kilodalton proteins of tomato and of a basic PR-1 of tobacco with inhibitory activity against Phytophthora infestans. AB - Three distinct basic 14-kD proteins, P14a, P14b, and P14c, were isolated from tomato (Lycopersicon esculentum Mill. cv Baby) leaves infected with Phytophthora infestans. They exhibited antifungal activity against P. infestans both in vitro (inhibition of zoospore germination) and in vivo with a tomato leaf disc assay (decrease in infected leaf surface). Serological cross-reactions and amino acid sequence comparisons showed that the three proteins are members of the PR-1 group of pathogenesis-related (PR) proteins. P14a and P14b showed high similarity to a previously characterized P14, whereas P14c was found to be very similar to a putative basic-type PR-1 from tobacco predicted from isolated DNA clones. This protein, named PR-1 g, was purified from virus-infected tobacco (Nicotiana tabacum Samsun NN) leaves and characterized by amino acid microsequencing, along with the well-known acidic tobacco PR-1a, PR-1b, and PR-1c. The various tomato and tobacco PR-1 proteins were compared for their biological activity and found to display differential fungicidal activity against P. infestans in both the in vitro and in vivo assays, the most efficient being the newly characterized tomato P14c and tobacco PR-1g. PMID- 7784504 TI - The choice of reducing substrate is altered by replacement of an alanine by a proline in the FAD domain of a bispecific NAD(P)H-nitrate reductase from birch. AB - Differences in the amino acid sequence between the bispecific NAD(P)H-nitrate reductase of birch (Betula pendula Roth) and the monospecific NADH-nitrate reductases of a variety of other higher plants have been found at the dinucleotide-binding site in the FAD domain. To pinpoint amino acid residues that determine the choice of reducing substrate, we introduced mutations into the cDNA coding for birch nitrate reductase. These mutations were aimed at replacing certain amino acids of the NAD(P)H-binding site by conserved amino acids located at identical positions in NADH-monospecific enzymes. The mutated cDNAs were integrated into the genome of tobacco by Agrobacterium-mediated transformation. Transgenic tobacco (Nicotiana tabacum) plants were grown on a medium containing ammonium as the sole nitrogen source to keep endogenous tobacco nitrate reductase activity low. Whereas some of the mutated enzymes showed a slight preference for NADPH, as does the nonmutated birch enzyme, the activity of some others greatly depended on the availability of NADH and was low with NADPH alone. Comparison of the mutations reveals that replacement of a single amino acid in the birch sequence (alanine871 by proline) is critical for the use of reducing substrate. PMID- 7784505 TI - Correct processing of the kiwifruit protease actinidin in transgenic tobacco requires the presence of the C-terminal propeptide. AB - A 355 cauliflower mosaic virus promoter and a tapetum-specific promoter were used to direct the synthesis in tobacco of preproactinidin and a derivative that lacked a C-terminal extension. Preproactinidin was processed into a form that migrated identically on protein gels with mature actinidin extracted from kiwifruit. This protein was proteolytically active in vitro, and high-level accumulation of this protein appeared to be detrimental to plant growth. Plants expressing an actinidin cDNA construct that lacked the sequence encoding the C terminal propeptide were phenotypically normal but accumulated N-proactinidin, which was proteolytically active in vitro but did not self-cleave to mature actinidin. In transgenic tobacco, the C-terminal extension of actinidin is therefore required for correct processing. PMID- 7784506 TI - Induction of apoplastic invertase of Chenopodium rubrum by D-glucose and a glucose analog and tissue-specific expression suggest a role in sink-source regulation. AB - Photoautotrophic suspension-culture cells of Chenopodium rubrum that were shifted to mixotrophic growth by adding glucose were used as model system to investigate the influence of the source-sink transition in higher plants on the expression and enzyme activities of intracellular and extracellular invertases. The complete cDNA coding for an extracellular invertase was cloned and sequenced from C. rubrum, and its identity has been proven by heterologous expression in Saccharomyces cerevisiae. The higher activity of extracellular invertase after preincubation in the presence of glucose was paralleled by an increased expression of the corresponding gene. The induction by glucose could be mimicked by the nonmetabolizable glucose analog 6-deoxyglucose. Both enzyme activity and mRNA level of extracellular invertase showed a sink-tissue-specific distribution in plants. The activity of neutral and acidic intracellular invertases were not affected by preincubation of autotrophic tissue cultures with sugars, nor did they show a tissue-specific distribution in plants. The data suggest that apoplastic invertase not only has an important function in phloem unloading and carbohydrate partitioning between source and sink tissues but may also have a role in establishing metabolic sinks. PMID- 7784507 TI - Purification, characterization, and intracellular localization of glycosylated protein disulfide isomerase from wheat grains. AB - Wheat (Triticum aestivum) storage proteins fold and assemble into complexes that are linked by intra- and intermolecular disulfide bonds, but it is not yet clear whether these processes are spontaneous or require the assistance of endoplasmic reticulum (ER)-resident enzymes and molecular chaperones. Aiming to unravel these processes, we have purified and characterized the enzyme protein disulfide isomerase (PDI) from wheat endosperm, as well as studied its developmental expression and intracellular localization. This ER-resident enzyme was previously shown to be involved in the formation of disulfide bonds in secretory proteins. Wheat PDI appears as a 60-kD glycoprotein and is among the most abundant proteins within the ER of developing grains. PDI is notably upregulated in developing endosperm in comparison to embryos, leaves, and roots. In addition, the increase in PDI expression in grains appears at relatively early stages of development, preceding the onset of storage protein accumulation by several days. Subcellular localization analysis and immunogold labeling of electron micrographs showed that PDI is not only present in the lumen of the ER but is also co-localized with the storage proteins in the dense protein bodies. These observations are consistent with the hypothesis that PDI is involved in the assembly of wheat storage proteins within the ER. PMID- 7784508 TI - Purification and characterization of a DNA strand transferase from broccoli. AB - A protein with DNA binding, renaturation, and strand-transfer activities has been purified to homogeneity from broccoli (Brassica oleracea var italica). The enzyme, broccoli DNA strand transferase, has a native molecular mass of at least 200 kD and an apparent subunit molecular mass of 95 kD and is isolated as a set of isoforms differing only in charge. All three activities are saturated at very low stoichiometry, one monomer per approximately 1000 nucleotides of single stranded DNA. Strand transfer is not effected by nuclease activity and reannealing, is only slightly dependent on ATP, and is independent of added Mg2+. Transfer requires homologous single- and double-stranded DNA and at higher enzyme concentrations results in very high molecular mass complexes. As with Escherichia coli RecA, transfer by broccoli DNA strand transferase depends strongly on the presence of 3' homologous ends. PMID- 7784510 TI - Alteration of seed fatty acid composition by an ethyl methanesulfonate-induced mutation in Arabidopsis thaliana affecting diacylglycerol acyltransferase activity. AB - In characterizing the enzymes involved in the formation of very long-chain fatty acids (VLCFAs) in the Brassicaceae, we have generated a series of mutants of Arabidopsis thaliana that have reduced VLCFA content. Here we report the characterization of a seed lipid mutant, AS11, which, in comparison to wild type (WT), has reduced levels of 20:1 and 18:1 and accumulates 18:3 as the major fatty acid in triacylglycerols. Proportions of 18:2 remain similar to WT. Genetic analyses indicate that the fatty acid phenotype is caused by a semidominant mutation in a single nuclear gene, designated TAG1, located on chromosome 2. Biochemical analyses have shown that the AS11 phenotype is not due to a deficiency in the capacity to elongate 18:1 or to an increase in the relative delta 15 or delta 12 desaturase activities. Indeed, the ratio of desaturase/elongase activities measured in vitro is virtually identical in developing WT and AS11 seed homogenates. Rather, the fatty acid phenotype of AS11 is the result of reduced diacylglycerol acyltransferase activity throughout development, such that triacylglycerol biosynthesis is reduced. This leads to a reduction in 20:1 biosynthesis during seed development, leaving more 18:1 available for desaturation. Thus, we have demonstrated that changes to triacylglycerol biosynthesis can result in dramatic changes in fatty acid composition and, in particular, in the accumulation of VLCFAs in seed storage lipids. PMID- 7784509 TI - Plasma membrane intrinsic proteins of Beta vulgaris L. AB - The plasma membrane (PM) of higher plants contains numerous proteins; however, due to their low abundance, only a few have been identified and characterized by direct biochemical approaches. The major intrinsic protein (MIP) family is a class of highly hydrophobic integral membrane proteins thought to function as channels that facilitate the passage of water, small solutes, and possibly other moieties through the membrane. A family of PM intrinsic proteins was purified and characterized from PM vesicles derived from storage tissue of Beta vulgaris L. using the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate. This PM intrinsic protein-enriched fraction also contains high levels of UDP glucose:(1,3)-beta-glucan (callose) synthase activity. Dithiothreitol is required to visualize the monomeric species of these highly hydrophobic integral membrane proteins. Sequence analysis of tryptic fragments derived from polypeptides of 31 and 27 kD revealed significant homologies to plant MIPs identified from cloned sequences. These MIPs include clone 7a from pea and RD28 from Arabidopsis, both of which are water-stress proteins, a tomato ripening-associated membrane protein, and PIP 2b, a PM-bound water channel protein from Arabidopsis. MIPs, therefore, represent abundantly occurring components of PMs derived from beet storage tissue. PMID- 7784511 TI - Ascorbate free radical reductase mRNA levels are induced by wounding. AB - A cDNA clone encoding ascorbate free radical (AFR) reductase (EC 1.6.5.4) was isolated from tomato (Lycopersicon esculentum Mill.) and its mRNA levels were analyzed. The cDNA encoded a deduced protein of 433 amino acids and possessed amino acid domains characteristic of flavin adenine dinucleotide- and NAD(P)H binding proteins but did not possess typical eukaryotic targeting sequences, suggesting that it encodes a cytosolic form of AFR reductase. Low-stringency genomic DNA gel blot analysis indicated that a single nuclear gene encoded this enzyme. Total ascorbate contents were greatest in leaves, with decreasing amounts in stems and roots and relatively constant levels in all stages of fruit. AFR reductase activity was inversely correlated with total ascorbate content, whereas the relative abundance of AFR reductase mRNA was directly correlated with enzyme activity in tissues examined. AFR reductase mRNA abundance increased dramatically in response to wounding, a treatment that is known to also induce ascorbate dependent prolyl hydroxylation required for the accumulation of hydroxyproline rich glycoproteins. In addition, AFR reductase may contribute to maintaining levels of ascorbic acid for protection against wound-induced free radical mediated damage. Collectively, the results suggest that AFR reductase activity is regulated at the level of mRNA abundance by low ascorbate contents or by factors that promote ascorbate utilization. PMID- 7784512 TI - Cloning of a harvest-induced beta-galactosidase from tips of harvested asparagus spears. PMID- 7784513 TI - Nucleotide sequence of the Rhodobacter capsulatus hemB gene. PMID- 7784514 TI - Nucleotide sequence of the Rhodobacter capsulatus hemE gene. PMID- 7784515 TI - Identification of a cell cycle-related gene, cyclin, in Nicotiana tabacum (L.). PMID- 7784516 TI - Cloning and nucleotide sequence of the S7-RNase from Nicotiana alata Link and Otto. PMID- 7784517 TI - Nucleotide sequence of a cDNA clone encoding caffeoyl-coenzyme A 3-O methyltransferase of Stellaria longipes (Caryophyllaceae). PMID- 7784518 TI - A cDNA encoding ribosomal protein S4e from cotton (Gossypium hirsutum L.). PMID- 7784520 TI - Sequencing and analysis of a calmodulin cDNA from pea (Pisum sativum L. var Alaska). PMID- 7784519 TI - Sequence of a cDNA encoding carbonic anhydrase from barley. PMID- 7784522 TI - Complete cDNA and genomic sequence encoding a flooding-responsive gene from maize (Zea mays L.) homologous to xyloglucan endotransglycosylase. PMID- 7784521 TI - Isolation, sequencing, and analysis of a calmodulin-like cDNA from pea (Pisum sativum L. var Alaska). PMID- 7784523 TI - The cDNA sequence of a cauliflower apetala-1/squamosa homolog. PMID- 7784524 TI - cDNA clones encoding beta-ketoacyl-acyl carrier protein synthase III from Cuphea wrightii. PMID- 7784525 TI - Characterization of membrane-bound small GTP-binding proteins from Nicotiana tabacum. AB - We have cloned nine cDNAs encoding small GTP-binding proteins from leaf cDNA libraries of tobacco (Nicotiana tabacum). These cDNAs encode distinct proteins (22-25 kD) that display different levels of identity with members of the mammalian Rab family: Nt-Rab6 with Rab6 (83%), Nt-Rab7a-c with Rab7 (63-70%), and Nt-Rab11a-e with Rab11 (53-69%). Functionally important regions of these proteins, including the "effector binding" domain, the C-terminal Cys residues for membrane attachment, and the four regions involved in GTP-binding and hydrolysis, are highly conserved. Northern and western blot analyses show that these genes are expressed, although at slightly different levels, in all plant tissues examined. We demonstrate that the plant Rab5, Rab6, and Rab11 proteins, similar to their mammalian and yeast counterparts, are tightly bound to membranes and that they exhibit different solubilization characteristics. Furthermore, we show that the yeast GTPase-activating protein Gyp6, shown to be specifically required to control the GTP hydrolysis of the yeast Ypt6 protein, could interact with tobacco GTP-binding proteins. It increases in vitro the GTP hydrolysis rate of the wild-type Nt-Rab7 protein. In addition, it also increases, at different levels, the GTP hydrolysis rates of a Nt-Rab7m protein with a Rab6 effector domain and of two other chimaeric Nt-Rab6/Nt-Rab7 proteins. However, it does not interact with the wild-type Nt-Rab6 protein, which is most similar to the yeast Ypt6 protein. PMID- 7784527 TI - 4-coumarate:coenzyme a ligase from loblolly pine xylem. Isolation, characterization, and complementary DNA cloning. AB - 4-Coumarate:CoA ligase (4CL, EC 6.2.1.12) was purified from differentiating xylem of loblolly pine (Pinus taeda L.). The pine enzyme had an apparent molecular mass of 64 kD and was similar in size and kinetic properties to 4CL isolated from Norway spruce. The pine enzyme used 4-coumaric acid, caffeic acid, ferulic acid, and cinnamic acid as substrates but had no detectable activity using sinapic acid. 4CL was inhibited by naringenin and coniferin, products of phenylpropanoid metabolism. Although the lignin composition in compression wood is higher in p hydroxyphenyl units than lignin from normal wood, there was no evidence for a different form of 4CL enzyme in differentiating xylem that was forming compression wood. cDNA clones for 4CL were obtained from a xylem expression library. The cDNA sequences matched pine xylem 4CL protein sequences and showed 60 to 66% DNA sequence identity with 4CL sequences from herbaceous angiosperms. There were two classes of cDNA obtained from pine xylem, and the genetic analysis showed that they were products of a single gene. PMID- 7784528 TI - Cardiac function and behavioral reactivity during infancy. AB - Longitudinal cardiac data from the end of the fetal period to 21 months of age were examined for change and stability over age and relations to the temperamental characteristics of high and low reactivity at 4 months of age and fear to the unfamiliar in the second year. Heart period and power in the cardiac spectra changed dramatically over the first 2 years, and individual differences were not preserved until 9-14 months of age. Sleep heart period at 2 weeks of age and low frequency power at 2 months of age were better predictors of the temperamental categories than later measures of the same variables, suggesting that cardiac function early in life may be an especially sensitive index of temperamental qualities. PMID- 7784529 TI - Fear conditioning, preparedness, and the contingent negative variation. AB - Psychophysiological research on preparedness has previously focused on autonomic nervous system parameters. The present study used electrocortical indices of fear conditioning. Subjects (n = 10) were tested under fear-relevant and fear irrelevant conditions (1 week apart, order of conditions counterbalanced). Each condition comprised acquisition and extinction sessions. The contingent negative variation (CNV) was elicited in anticipation of forewarned slides (fear relevant: small animals; fear irrelevant: landscapes). In acquisition, reinforced conditioned stimulus (CS+) (but not nonreinforced conditioned stimulus [CS-]) slides were followed by white noise as an unconditioned stimulus (UCS). In extinction, the UCS was omitted. In the fear-relevant condition, CNV amplitude was significantly larger for CS+ than CS- in both acquisition and extinction. In the fear-relevant condition, CNV amplitude was significantly larger for CS+ than CS- in both acquisition and extinction. In the fear-irrelevant condition, CNV differentiation between CS+ and CS- was weak in both sessions. CNV was significantly larger in the fear-relevant than in the fear-irrelevant condition, for CS+ but not CS-. The findings are consistent with a preparedness interpretation and suggest that CNV under such circumstances may represent an automatic affective response to fear-relevant stimuli. Electrocortical measures could be particularly useful in examining information processing mechanisms in phobia and cognition-affect relationships generally. PMID- 7784526 TI - Biochemical, physiological, and molecular characterization of sucrose synthase from Daucus carota. AB - Sucrose synthase (EC 2.4.1.13) from carrot (Daucus carota) is a tetramer with a molecular mass of 320 kD and subunits of 80 kD. The enzyme has a pH optimum of 7.0 (cleavage direction). Maximal activities were measured at 55 degrees C. The Km for Suc was estimated as 87 mM and for UDP as 0.39 mM. Fructose acts as a noncompetitive inhibitor with an inhibition constant of 17.2 mM. In contrast, glucose inhibits carrot sucrose synthase uncompetitively with an inhibition constant of 4.3 mM. cDNA clones encoding a single class of sucrose synthase polypeptide were isolated and sequenced. DNA gel blot analysis also indicated the occurrence of only one to two genes. The deduced amino acid sequence of the carrot enzyme is highly homologous to the sucrose synthase sequences of tomato, potato, and bean. A comparison of the cDNA-derived amino acid sequence with the SS1- and SS2-type sucrose synthase sequences of the monocot plants maize, rice, and barley showed that the carrot enzyme is neither of the SS1 nor of the SS2 type. High enzyme activity was found in roots and petioles of developing carrot plants, with maximal activity in roots at the transition of primary roots to tap roots. Enzyme activity was highly correlated with both polypeptide and transcript levels, indicating that gene expression is regulated mainly at the mRNA level in the different tissues and organs of developing carrot plants. PMID- 7784530 TI - Language, memory, and aging: an electrophysiological exploration of the N400 during reading of memory-demanding sentences. AB - Twenty-four young and 24 middle-aged academics carried out a language recognition task in which sentences were presented that made either a high or a low demand on working memory (WM). The sentences ended either normally (i.e., congruent) or with an incongruous word. Middle-aged subjects had smaller WM scores, a marginally slowed down recognition performance, and a smaller and delayed N400 component. The event-related potential (ERP) difference between congruent and incongruent endings was smaller in the high-load condition for younger subjects and totally disappeared for the middle-aged subjects. ERPs for all subjects showed a WM-related positivity in the middle of the sentence and a WM-related negativity at the sentence ending. These shifts could be associated with either storage and retrieval processes or with clause wrap-up processes. Most ERP effects were dependent on WM capacity. Age differences in sentence processing are not simply explained by age itself but depend to a large extent on individual memory capacity. PMID- 7784531 TI - Response complexity and precue interval effects on the lateralized readiness potential. AB - Fundamental properties of an important new tool in cognitive electrophysiology, the lateralized readiness potential (LRP), were examined in two experiments. Experiment 1 resolved an apparent inconsistency in the literature by demonstrating that this response-specific lateralization is larger preceding complex then preceding simple finger movements. In Experiment 2, the foveally presented precue, which indicated hand of response, preceded the go/no-go stimulus by 0, 100, 300, or 1,400 ms. Analyses of LRP latency indicated that hand specific preparation began earlier with longer foreperiods but was temporally linked to the reaction stimulus as well as the precue. Although the degree of lateralization did not predict reaction speed in either study, a nonlateralized, response-locked negativity was larger prior to faster reactions. PMID- 7784532 TI - Mental effort during active and passive coping: a dual-task analysis. AB - This study was designed to examine the invested mental effort during active and passive coping by means of performance data. Dual-task performance was measured while subjects coped with a situation, either actively or passively. Thirty-six male students worked on a primary mental arithmetic task (MAT) and a secondary choice reaction time task simultaneously. Half of the sample could avoid an aversive tone by performing well on the MAT. For the remaining half, their performance had no influence on the tone. The aversive tone stimulation of these subjects was yoked to a "partner," in the first group. Subjects with control showed elevated cardiovascular responses and inferior secondary task performance than subjects without control. No differences were found in the performance on the MAT. These results were in line with the assumption that subjects with control spent more effort on the primary task. Subjects under the active coping condition probably payed more attention to the tone, which consumed more cognitive resources. PMID- 7784533 TI - Sources of P300 attenuation after head injury: single-trial amplitude, latency jitter, and EEG power. AB - Single trial amplitude, latency jitter, and electroencephalographic (EEG) power were examined as sources of the group difference in averaged P300 amplitude among 15 traumatically brain injured and 20 control individuals in an auditory oddball paradigm. Mean amplitude of the individual trials was highly correlated with the amplitude of the averaged P300, with little additional unique variance attributable to latency jitter or EEG power. The group difference in P300 amplitude was also explained by the mean amplitude of the single trials. These results support the robustness of the evtent-related potential averaging technique within the paradigm used. PMID- 7784534 TI - P300 topography in Alzheimer's disease. AB - This study assessed whether P300 scalp topography distinguished subjects with Alzheimer's disease (AD) from controls. Specifically, it was predicted that the AD group would show maximum P300 amplitude over frontal areas and the largest P300 reduction over parietal and left hemisphere areas. These hypotheses were tested using a standard auditory oddball paradigm to compare 26 AD subjects and 26 controls matched on age, sex, handedness, and education. P300 was measured at frontal, central, parietal, and occipital sites over left and right hemispheres and along the midline. Results revealed that the distribution of P300 was different for the two groups such that the controls manifested a maximum over parietal areas, whereas the AD subjects showed a maximum at frontal sites with the largest reductions in P300 over parietal areas. No hemispheric differences in P300 were found. These results are consistent with the hypothesis that P300 represents the activity of multiple neural generators that are differentially disrupted by the disease process. PMID- 7784535 TI - Attentional modulation of startle in psychosis-prone college students. AB - Attentional modulation of startle eyeblink was studied in college students putatively at risk for psychosis and in normal controls. At-risk subjects had extreme scores on scales for either anhedonia or perceptual aberration-magical thinking (per-mags). Subjects were presented with to-be-attended and to-be ignored tones; white noise startle probes were presented at lead intervals of 60, 120, 240, or 2,000 ms following the onset of attended and ignored tones and during intertone intervals. Controls showed greater inhibition of startle blink at 120 ms and greater facilitation at 2,000 ms during to-be-attended than to-be ignored tone, demonstrating attentional modulation of prepulse inhibition and facilitation. Both at-risk groups showed normal overall levels of early inhibition and late facilitation. However, per-mags failed to show attentional modulation of either inhibition at 120 ms or facilitation at 2,000 ms; anhedonics showed no modulation of inhibition and modulation of facilitation was delayed in development. The results for the per-mags are strikingly similar to those observed in schizophrenic patients and suggest that these deficits index a trait linked vulnerability to disorders in the schizophrenic spectrum. PMID- 7784536 TI - The N400 as a function of the level of processing. AB - In a semantic priming paradigm, the effects of different levels of processing on the N400 were assessed by changing the task demands. In the lexical decision task, subjects had to discriminate between words and nonwords, and in the physical task, subjects had to discriminate between uppercase and lowercase letters. The proportion of related versus unrelated word pairs differed between conditions. A lexicality test on reaction times demonstrated that the physical task was performed nonlexically. Moreover, a semantic priming reaction time effect was obtained only in the lexical decision task. The level of processing clearly affected the event-related potentials. An N400 priming effect was only observed in the lexical decision task. In contrast, in the physical task a P300 effect was observed for either related or unrelated targets, depending on their frequency of occurrence. Taken together, the results indicate that an N400 priming effect is only evoked when the task performance induces the semantic aspects of words to become part of an episodic trace of the stimulus event. PMID- 7784537 TI - Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring. AB - The circadian distribution of motor activity and immobility of 14 unmedicated narcoleptics and matched controls was evaluated by monitoring continuous wrist motor activity 5 successive days and nights at home. Sleep was also assessed by sleep logs. The amplitude of the circadian rhythm of motor activity and immobility was significantly lower in narcoleptics than in controls. The variables that best distinguish narcoleptics from controls were the diurnal and nocturnal mean duration of uninterrupted immobility, which can be explained by excessive daytime sleepiness and frequent nocturnal awakenings, respectively. Thus, measures of diurnal and nocturnal motor activity and immobility appear useful for the objective assessment of some of the sleep-wakefulness manifestations of narcolepsy. PMID- 7784538 TI - Removing the heart from the brain: compensation for the pulse artifact in the photon migration signal. AB - Various factors, including variations in the concentration of hemoglobin, determine changes in the transparency of living tissue to near-infrared light. Hence, optical measures have been proposed as a noninvasive method for investigating regional changes in brain activity. However, the amount of near infrared light traversing a region of the head is also influenced by the periodic changes in blood pressure that occur during the cardiac cycle (pulse). These large changes may obscure smaller, localized events associated with brain activity. We developed a least-squares regression algorithm for compensating for the artifact introduced by the pulse. This procedure takes into account beat-to beat variability in heart rate and differences in the shape of the pulse among subjects and among recording conditions. PMID- 7784539 TI - Professor Dorothy Hodgkin. PMID- 7784541 TI - Earning a living. PMID- 7784540 TI - Fundamentals of drug design from a biophysical viewpoint. PMID- 7784542 TI - Patients vs. paperwork. PMID- 7784544 TI - Using virtual reality to teach radiographic positioning. AB - Using virtual reality to teach radiographic positioning overcomes many of the limitations of traditional teaching methods and offers several unique advantages. This article describes a virtual reality prototype that could be used to teach radiographic positioning of the elbow joint. By using virtual reality, students are able to see the movement of bones as the arm is manipulated. The article also describes the development and challenges of using virtual reality in medical education. PMID- 7784543 TI - Radiography education in the United Kingdom. AB - The U.S. system of educating radiologic technologists is changing to meet the demands of an evolving health care work force. As a result, the educational standards and role of tomorrow's radiologic technologist will be very different from those of today. Many of the changes being considered by radiologic science professionals in the United States already have occurred in the United Kingdom. Beginning this year, for example, all entry-level radiographers in the United Kingdom must be graduates of a baccalaureate degree program. This article describes how radiography programs in the United Kingdom made the transition to a baccalaureate degree standard. It also examines how the role and scope of practice of U.K. technologists changed following the increase in educational standards. PMID- 7784545 TI - Recording the radiographic image. PMID- 7784546 TI - Computer-based instruction. PMID- 7784547 TI - Split screen contiguous ultrasound imaging. PMID- 7784548 TI - Hedis 2.0 and its impact on radiology. PMID- 7784549 TI - Thrombolysis in interventional radiology. PMID- 7784550 TI - Health care reform and human resources. PMID- 7784551 TI - Neuroradiology: a historical perspective. PMID- 7784552 TI - Superior hypogastric plexus block for chronic pelvic pain in the presence of endometriosis: CT techniques and results. AB - PURPOSE: To evaluate the use of superior hypogastric plexus block with computed tomographic (CT) guidance in patients with endometriosis and chronic pelvic pain. MATERIALS AND METHODS: Seven blocks were performed on an outpatient basis in five women with endometriosis and pelvic pain. In the first four patients, one or two 20-gauge, 15-cm needles were placed anterior to the spine at the common iliac bifurcation from a posterior approach. In the fifth patient, the block was performed from an anterior approach with a single needle. RESULTS: One procedure resulted in mild pain relief, three in considerable pain relief, one in complete midline pain relief with no change in the lateral pain, and one in complete pain relief. One procedure was terminated because anesthetic was injected into the peritoneal cavity. There were no other complications. CONCLUSION: CT-guided superior hypogastric plexus block is easily performed and can be used to assess whether chronic pelvic pain can be attenuated by blocking the superior hypogastric plexus. PMID- 7784553 TI - Mechanism of colloidal particle uptake into the lymphatic system: basic study with percutaneous lymphography. AB - PURPOSE: To examine the extracellular (dispersed particles) and intracellular (phagocytosed particles) colloidal particle transport from subcutaneous tissue into the lymphatic system. MATERIALS AND METHODS: Perfluorocarbon emulsions LA11063 (mean particle diameter, 0.34 micron) and ZY12149 (mean particle diameter, 0.06 micron) were individually injected into the dorsal skin of the hind foot of rabbits. Lymph flow rates and particle concentrations were determined in prenodal lymph fluid after injection, with and without massage of the skin over the injection site. RESULTS: In the first 24 hours after injection, extracellular colloid flux was substantially larger than intracellular flux. Lymph flow rates and colloid concentrations increased substantially with massage. Extracellular LA11063 flux was smaller than ZY12149 flux, whereas intracellular LA11063 flux exceeded ZY12149 flux. CONCLUSION: Transport of colloids into lymphatic vessels is dependent on particle size. Both extracellular and intracellular pathways are utilized. External tissue movement contributes substantially to the rate of particle uptake via both pathways. PMID- 7784554 TI - Staging of suspected breast cancer: effect of MR imaging and MR-guided biopsy. AB - PURPOSE: To investigate the effect of contrast material-enhanced magnetic resonance (MR) imaging on staging of breast cancer in patients with mammographically or clinically suspected tumor. MATERIALS AND METHODS: One hundred seventy-six patients underwent breast MR imaging at 1.5 T before excisional biopsy of a suspicious mammographic or palpable abnormality. Diagnostic imaging studies in patients with biopsy-proved or presumed breast carcinoma were reviewed. RESULTS: Sixty-four patients met the study criteria. MR imaging enabled detection of all 57 invasive breast cancers and nine of 15 in situ cancers. In 22 patients (34%), MR imaging depicted one or more cancers not visible at mammography, 13 (20%) of which were unsuspected multifocal or diffuse disease. As a result of the increased sensitivity of MR imaging compared with that of mammography, clinical staging and subsequent treatment were altered in seven patients (11%). CONCLUSION: MR imaging allows detection of mammographically and clinically occult foci of carcinoma in patients with suspected breast cancer. PMID- 7784555 TI - Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. AB - PURPOSE: To determine whether sonography could help accurately distinguish benign solid breast nodules from indeterminate or malignant nodules and whether this distinction could be definite enough to obviate biopsy. MATERIALS AND METHODS: Seven hundred fifty sonographically solid breast nodules were prospectively classified as benign, indeterminate, or malignant. Benign nodules had no malignant characteristics and had either intense homogeneous hyperechogenicity or a thin echogenic pseudocapsule with an ellipsoid shape or fewer than four gentle lobulations. Sonographic classifications were compared with biopsy results. The sensitivity, specificity, and negative and positive predictive values of the classifications were calculated. RESULTS: Benign histologic features were found in 625 (83%) lesions; malignant histologic features, in 125 (17%). Of benign lesions, 424 had been prospectively classified as benign. Two lesions classified as benign were found to be malignant at biopsy. Thus, the classification scheme had a negative predictive value of 99.5%. Of 125 malignant lesions, 123 were correctly classified as indeterminate or malignant (98.4% sensitivity). CONCLUSION: Sonography can be used to accurately classify some solid lesions as benign, allowing imaging follow-up rather than biopsy. PMID- 7784556 TI - Dynamic three-dimensional imaging with partial k-space sampling: initial application for gadolinium-enhanced rate characterization of breast lesions. AB - PURPOSE: To evaluate a method to monitor gadolinium enhancement patterns at magnetic resonance (MR) imaging with high temporal resolution and full coverage through both breasts. MATERIALS AND METHODS: In 12 patients with 13 masses, including nine carcinoma, nonenhanced three-dimensional MR imaging was performed with full-matrix resolution. At dynamic imaging, 32 serial passes were made during bolus administration of contrast material, and temporal resolution was reduced to 12 seconds by collecting the central (low spatial frequency) 32 x 16 or 16 x 16 phase-encode views. Full-matrix dynamic images were reconstructed by complementing central phase-encode data with precontrast data from peripheral high-spatial-frequency views. RESULTS: Results at time-course analysis with a mono-exponential saturation model indicated malignant lesions tend to show rapid (< 60 seconds) contrast change relative to benign masses and normal tissues. One cancer displayed an exceptionally slow contrast change (260 seconds). CONCLUSION: The technical objectives of full tissue coverage, rapid temporal sampling, and quantification of enhancement curves are met with this method for certain lesions (> 5 mm in largest diameter). PMID- 7784557 TI - Management of solid breast nodules: what is the role of sonography? PMID- 7784558 TI - Breast MR imaging with commercially available techniques: radiologic-pathologic correlation. AB - PURPOSE: To evaluate the clinical utility of dynamic gadolinium-enhanced magnetic resonance (MR) imaging of the breast with commercially available techniques in patients scheduled for excisional biopsy. MATERIALS AND METHODS: A total of 91 breast abnormalities, 70 benign and 21 malignant, were evaluated. Thin-section three-dimensional gradient-echo images were obtained before and 2, 4, and 7 minutes after injection of contrast material. Three radiologists prospectively evaluated the mammograms and MR images. RESULTS: The areas under the receiver operating characteristic curves were 0.820 for mammography and 0.893 for MR imaging (P = .67). Sensitivity of MR imaging was 82.5%, compared with 74.6% for mammography. Specificity of MR imaging was 82.5%, compared with 79.1% for mammography. Enhancement profiles showed early intense enhancement in malignancies but considerable overlap with enhancement of benign disease. CONCLUSION: Breast MR imaging is a slightly more sensitive modality than mammography but not a highly specific technique for evaluating breast lesions. It has utility in several clinical situations but should not be used as a substitute for biopsy or general screening. PMID- 7784559 TI - Breast dose during electron-beam CT: measurement with film dosimetry. AB - PURPOSE: To measure the breast dose and dose distribution from examinations performed with electron-beam computed tomography (CT). MATERIALS AND METHODS: Radiographic film was placed bilaterally at three depths in the breasts of an anthropomorphic phantom and exposed with clinically relevant protocols. The average breast dose and the dose distribution were obtained from the digitized and calibrated film and compared with those obtained with conventional CT. RESULTS: Breast doses from electron-beam CT chest, coronary artery calcium, and cardiac function examinations were 21.9, 2.87, and 1.55 mGy, respectively. Within the breast, the dose decreased linearly by a factor of three from the axilla to the sternum. The breast dose from a conventional CT chest examination ranged from 18 to 33 mGy and did not vary substantially across the breast. CONCLUSION: For chest examinations, the average breast dose from an electron-beam CT scanner was comparable to that from conventional CT scanners, despite the differences in dose distribution. PMID- 7784560 TI - Electron-beam CT: use of a calibration phantom to reduce variability in calcium quantitation. AB - PURPOSE: To measure scanner and patient variation in computed tomographic (CT) numbers for electron-beam CT and to determine the ability of calibration phantoms to reduce variability in calcium quantitation. MATERIALS AND METHODS: Two calibration phantoms were imaged to ensure longitudinal homogeneity and to determine the short-term intrascanner variation in CT numbers. Each phantom set was imaged twice a day for 14 weeks to determine intra- and interscanner variation. Data from examinations of 167 patients that included the phantom were analyzed to determine the intra- and interpatient variation in CT numbers of objects with known calcium concentrations. RESULTS: The calibration reduced scanner variations by approximately 25%. The calcium concentration associated with a CT number of 130 HU varied from 77.1 to 136.4 mg/cm3 and was dependent on patient girth, sex, smoking history, and image level. CONCLUSION: Scanner and patient variations in CT numbers in electron-beam CT can be reduced with a calibration phantom. In vitro and in vivo estimates of calcium concentration had a precision of 2% and 7%, respectively. PMID- 7784561 TI - Breast cancer staging with contrast material-enhanced MR imaging: should it change patient treatment? PMID- 7784562 TI - Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18] fluoro-2-deoxy-D-glucose uptake at PET. AB - PURPOSE: To study the precision of repeated 2-[fluorine-18]-fluoro-2-deoxy-D glucose (FDG) uptake measurements at positron emission tomography (PET) in patients with primary lung cancer. MATERIALS AND METHODS: Ten patients with untreated lung cancer underwent two dynamic FDG PET examinations after a 4-hour fast within 1 week. Kinetic modeling of tumor FDG uptake was performed on the basis of a three-compartment model. The tumor concentration of F-18 (standardized uptake value calculated on the basis of predicted lean body mass [SUV-lean]) was also measured 50-60 minutes after injection of a tracer. Blood glucose, insulin, and free fatty acid levels were monitored. RESULTS: SUV-lean and the FDG influx constant Ki were measured with a mean +/- standard deviation difference of 10% +/ 7 and 10% +/- 8, respectively, over repeated PET scans. The mean difference was reduced to 6% +/- 6 and 6% +/- 5 by multiplying SUV-lean and Ki by plasma glucose concentration. CONCLUSION: SUV-lean and graphical Ki can be measured reproducibly, supporting their use in quantitative FDG PET algorithms. PMID- 7784563 TI - Peripheral bronchopleural fistula: CT evaluation in 20 patients with pneumonia, empyema, or postoperative air leak. AB - PURPOSE: To assess the usefulness of standard and thin-section computed tomography (CT) in the examination of patients with possible bronchopleural fistulas (BPFs). MATERIALS AND METHODS: Twenty patients with known or suspected BPFs underwent CT. Twelve had pleural air and fluid collections; eight had air leaks. Fourteen patients also underwent thin-section CT. RESULTS: The BPF or its probable cause was visualized in all patients with air and fluid collections and in two of the patients with air leaks. BPFs due to bronchiectasis, necrotizing pneumonia, or alveolar cell carcinoma were identified in 10 patients. In four others, bronchiectasis was seen but the actual communication was not. In seven patients with postoperative air leaks, standard or thin-section CT demonstrated the air-leak source in only one. Thin-section CT was superior to standard CT in six of eight patients in whom the BPF or its probable cause was visible. CONCLUSION: Standard and thin-section CT are useful in the diagnosis and management of peripheral BPFs. PMID- 7784564 TI - Needle aspiration lung biopsy: reevaluation of the blood patch technique in an equine model. AB - PURPOSE: To reexamine the blood patch technique in a laboratory model of lung biopsy free of confounding clinical variables. MATERIALS AND METHODS: An equine model of lung biopsy was developed with an excised lobe connected to an insufflation bulb and pressure monitor. Patched and control unpatched punctures were made in the lung surface, and the pressure within the lung was raised to the maximum achievable. Whether air leakage from the puncture sites could be induced was determined and, if so, at what pressure it occurred. RESULTS: At statistical analysis with the Kaplan-Meier test and the Cox proportional hazards regression model, the difference between failure of the patched and unpatched punctures was statistically significant (P < .0001). CONCLUSION: The blood patch technique is effective in the laboratory setting and deserves reevaluation in a clinical series with updated biopsy techniques. PMID- 7784565 TI - Intracranial arteriovenous malformations: quantitative analysis of magnitude contrast MR angiography versus gradient-echo MR imaging versus conventional angiography. AB - PURPOSE: To quantitatively analyze magnitude contrast (MC) magnetic resonance (MR) angiography and gradient-echo (GRE) MR imaging for evaluation of persistent transnidal blood flow in intracranial arteriovenous malformations (AVMs) of various sizes before or after stereotaxic radiosurgery. MATERIALS AND METHODS: Thirty-three patients with AVMs underwent 42 MC MR angiographic (maximum intensity projection [MIP] and source imaging), GRE imaging with and without flow compensation, and conventional angiographic studies within 90 days of each other. RESULTS: For MIP, source, and GRE images, the sensitivities for detection of large AVMs (> 1 cm) were 95%, 100%, and 100%, respectively, and for small AVMs (< or = 1 cm) were 27%, 50%, and 67%, respectively. MC MR angiography and GRE imaging depicted all eight nidi that were completely thrombosed on conventional angiograms. CONCLUSION: GRE imaging and MC MR angiography reliably depict AVMs larger than 1 cm. GRE is more sensitive for detection of small residual nidi (< 1 cm). Source images must be evaluated to accurately assess low-flow lesions. Neither GRE nor MR angiography is reliable for detection of mean nidus diameters less than 0.36 cm. PMID- 7784566 TI - Intracolonic pressure and enemas in children: form follows function. PMID- 7784567 TI - Cerebrospinal fluid flow waveforms: analysis in patients with Chiari I malformation by means of gated phase-contrast MR imaging velocity measurements. AB - PURPOSE: To determine the features of the cardiac cycle-related cerebrospinal fluid (CSF) flow pulsations in with Chiari I malformation before and after decompressive surgery. MATERIALS AND METHODS: Fifteen patients and 23 healthy subjects underwent cine phase-contrast magnetic resonance imaging. Ten patients were also examined after decompressive surgery. Four regions of interest were selected in the upper cervical subarachnoid space and premedullary cistern. Velocity and fraction of the cardiac cycle waveforms were plotted, and amplitude, temporal, and CSF displacement parameters were assessed. RESULTS: In the Chiari I patients, impaired systolic and unaltered diastolic CSF flow pulsations immediately below the foramen magnum were identified. After surgery, the systolic flow pulsations immediately below the foramen magnum improved. Good correlation with post-surgical improvement was observed. CONCLUSION: CSF flow waveform analysis helps demonstrate abnormalities in CSF flow at the foramen magnum and the benefits of decompressive surgery in patients with the Chiari I malformation. PMID- 7784568 TI - Metabolic changes in acute and subacute cerebral infarctions: findings at proton MR spectroscopic imaging. AB - PURPOSE: To analyze the advantages of proton magnetic resonance (MR) spectroscopic imaging in the evaluation of acute and subacute cerebral infarcts. MATERIALS AND METHODS: Metabolite maps of choline-containing compounds, total creatine consisting of creatine and phosphocreatine, N-acetyl aspartate (NAA), and lactate were obtained in 23 patients with acute and subacute cerebral infarctions 1-35 days after onset of symptoms. Maps were obtained with a 1.5-T MR system with 32 x 32 phase-encoding steps. RESULTS: Distinct abnormal metabolite distributions could be detected in all lesions larger than 1 cm in diameter. In the center of infarcts with a diameter larger than the section thickness of 2 cm, NAA values decreased to 20% +/- 8 compared with contralateral brain as early as 1 day after onset of symptoms (P < .0001). Choline was reduced to 67% +/- 30 (not significant) and creatine to 51% +/- 22 (P = .0025). Large amounts of lactate were detected in all acute infarcts. Choline, creatine, and lactate values declined during the first 5 weeks after stroke. CONCLUSION: MR spectroscopic imaging allows visualization of metabolic changes in stroke with a reasonable spatial resolution. PMID- 7784569 TI - Moyamoya disease: comparison of assessment with MR angiography and MR imaging versus conventional angiography. AB - PURPOSE: To evaluate magnetic resonance (MR) angiography and MR imaging in assessment of moyamoya disease. MATERIALS AND METHODS: The cases of 26 patients with moyamoya disease were evaluated prospectively. After three-dimensional time of-flight 1.5-T MR angiography and MR imaging, images were evaluated in blinded separate interpretation. RESULTS: MR angiography and MR imaging accurately depicted 217 (82%) and 184 (70%) of 264 arteries, respectively, but the degree of stenosis was overestimated in the other arteries. Basal cerebral moyamoya vessels were depicted in all 52 hemispheres with conventional angiography and in 42 (81%) and 48 (92%) hemispheres with MR angiography and MR imaging, respectively. The respective sensitivity and specificity for diagnosis of moyamoya disease were 73% and 100% for MR angiography, 92% and 100% for MR imaging, and 92% and 100% for MR angiography plus MR imaging. CONCLUSION: Assessment of moyamoya disease is most thorough with MR angiography and MR imaging. PMID- 7784570 TI - MR imaging: quality assessment method and ratings at 33 centers. AB - PURPOSE: To outline a quality assessment method with peer review for magnetic resonance (MR) imaging. MATERIALS AND METHODS: Thirty-three providers in the Philadelphia area were rated on a random sample of 132 brain, 124 cervical spine, and 113 lower extremity MR imaging examinations performed during 1990. Blinded peer review was performed by panels of three subspecialty-trained academic radiologists. Technical performance, completeness, and report appropriateness of each MR imaging examination were evaluated. Aggregated scores were calculated to rate provider performance for each of the three parameters of quality. RESULTS: Two or three panelists assessed technical performance as inadequate in 15 cases, completeness as incomplete in 58 cases, and the interpretative report as inappropriate and affecting treatment in 72 cases. Eleven providers received an unsatisfactory rating on one or more parameters of quality. The association between unsatisfactory ratings and the use of low-field-strength (< or = 0.6-T) imagers was statistically significant (P < .008). CONCLUSION: Substantial deficiencies were identified in the performance of examinations and interpretation of MR images in the Philadelphia area in 1990. These findings indicate the need for a program to monitor quality of MR imaging. PMID- 7784571 TI - Triangular fibrocartilage in asymptomatic subjects: investigation of abnormal MR signal intensity. PMID- 7784572 TI - Evaluation of a non-breath-hold MR cholangiography technique. AB - PURPOSE: To evaluate prospectively a non-breath-hold magnetic resonance (MR) cholangiographic technique. MATERIALS AND METHODS: Twenty-nine non-breath-hold, heavily T2-weighted, turbo spin-echo MR cholangiograms were obtained in 28 patients and compared with 28 direct cholangiographic studies in 24 patients. RESULTS: MR cholangiography showed the intrahepatic ducts (IHDs) within the peripheral third of the liver and within the four hepatic segments in 100% of cases with dilated ducts. IHDs were seen in the peripheral third in 82% of cases with nondilated ducts and within the four hepatic segments in 91%. The extrahepatic duct (EHD), dilated and nondilated, was visualized in 90% of cases. Filling defects were identified in the EHD in 71% of cases and in the gallbladder in 100%. All obstructions were identified and their site and character accurately shown in most cases. The presence of IHD dilatation was accurately shown, and estimates of EHD and main pancreatic duct caliber correlated closely with those of direct cholangiography. CONCLUSION: Non-breath-hold MR cholangiography is a reliable method for depiction of the biliary system. PMID- 7784573 TI - Carcinoma of the head of the pancreas: evaluation of the pancreaticoduodenal veins with dynamic CT--potential for improved accuracy in staging. AB - PURPOSE: To determine if detection of abnormal dilatation of pancreaticoduodenal veins can improve the accuracy of computed tomographic (CT) staging of pancreatic adenocarcinoma. MATERIALS AND METHODS: CT scans obtained during bolus administration of contrast material in 86 patients (aged 34-85 years) with pancreatic head carcinoma were reviewed. The diameter of the small veins that surround the head of the pancreas was measured (normal diameter of gastrocolic trunk, < or = 7 mm; of anterior superior pancreaticoduodenal vein, < or = 4 mm; of posterior superior pancreaticoduodenal vein, < or = 4 mm). RESULTS: Twenty nine abnormally dilated peripancreatic veins were identified in 22 patients. Twenty-two of these dilated veins were in 16 patients with other CT criteria of tumor unresectability; seven dilated veins were in six patients with tumors deemed resectable at CT. All tumors in these latter six patients were unresectable at surgery. CONCLUSION: Although dilatation of these small peripancreatic veins without other CT criteria of tumor unresectability is an unusual finding, it may be a reliable sign of unresectable pancreatic carcinoma. PMID- 7784574 TI - Experimental gastrointestinal hemorrhage: detection with contrast-enhanced MR imaging and scintigraphy. AB - PURPOSE: To examine the use of O-methoxy poly(ethylene)glycol-O'-succinyl-N epsilon-poly(L-lysyl) gadolinium diethylenetriaminepentaacetic acid (MPEG-PL-Gd DTPA) as a potential magnetic resonance (MR) angiographic contrast agent for the detection of gastrointestinal (GI) bleeding. MATERIALS AND METHODS: MPEG-PL-Gd DTPA was used for blood pool enhancement, and MPEG-PL-technetium-99m DTPA was used for planar nuclear imaging studies. GI bleeding was tested in rats by controlled injection of contrast material-doped blood through a jejunostomy catheter. MR imaging was performed at 1.5 T. RESULTS: Ideal flip angle, used with a spoiled gradient-echo pulse sequence, was 40 degrees. The smallest amount of hemorrhage detected at MR imaging was 0.05 mL; at nuclear imaging it was 0.02 mL. With the superior spatial resolution of MR imaging, individual loops of contrast material-filled bowel were identified and bleeding points were pinpointed. CONCLUSION: GI hemorrhage can be easily detected at MR imaging if a long circulating macromolecular contrast agent is used to decrease the T1 of extravasated blood. PMID- 7784575 TI - The dangers of roentgenoscopy and methods of protection against them: state of the art, 1930s. PMID- 7784576 TI - Hepatic pseudolesion in the left lobe around the falciform ligament at helical CT. AB - PURPOSE: To determine the prevalence and possible cause of pseudolesions in the left hepatic lobe around the falciform ligament at hepatic helical computed tomography (CT). MATERIALS AND METHODS: Portal venous-dominant CT scans of 472 consecutive patients were reviewed. CT of the left hepatic lobe was performed after injection of contrast material into the portal vein in 73 patients, the hepatic artery in 32, and the internal thoracic artery in four. The scans were compared with those obtained at helical CT, and the findings were analyzed. RESULTS: Pseudolesions were seen on 64 (14%) of 472 helical CT scans and correlated well (accuracy, 96%) with portal perfusion defects. They were not more enhanced than the surrounding liver parenchyma at CT arteriography with hepatic artery injection but were enhanced in two patients at CT arteriography with internal thoracic artery injection. CONCLUSION: Pseudolesions are caused by portal perfusion defects and may receive an aberrant blood supply. PMID- 7784577 TI - Pancreaticogastrostomy and the Whipple procedure: radiographic appearance and complications. AB - PURPOSE: To evaluate the radiographic appearance of a pancreaticogastrostomy (PG) and its complications. MATERIALS AND METHODS: Seventy-two patients underwent pancreaticoduodenectomy and PG or pancreaticojejunostomy. Those who underwent PG and were evaluated postoperatively with T-tube cholangiography and upper gastrointestinal (UGI) series constitute the study group (n = 22; 10 men, 12 women; age range, 33-88 years). RESULTS: Twenty-one of the patients had a gastric filling defect radiographically detected. Four patients had clinically apparent delayed gastric emptying and one patient had a clinically apparent pancreatic fistula not detected radiographically. Two patients outside the study group had complications: One had a pancreatic fistula seen only with sinography, and one had a PG leak seen only with repeat UGI series and computed tomography (CT). CONCLUSION: PG caused a gastric filling defect in most patients. Suspected pancreatic fistulas are best confirmed with sinography, and suspected PG leaks may require repeat evaluation and CT. Clinical findings of delayed gastric emptying do not correlate with findings of UGI. PMID- 7784578 TI - Evaluation of 2-(3-aminobenzamido)-2-deoxy-D-glucose as a radiosensitizer. AB - PURPOSE: 3-Aminobenzamide (3-AB), an inhibitor of poly(adenosine diphosphate [ADP]-ribose) synthetase, functions as a radiosensitizer in several human tumor cell lines. 2-(3-AB)-2-deoxy-D-glucose (3-AB-G) was designed to increase preferentially the intracellular concentration of the drug in tumor cells. Both the toxicity and effectiveness of 3-AB-G as a radiosensitizer were determined. MATERIALS AND METHODS: The toxicity of 3-AB-G was measured in HeLa and Chinese hamster ovary cells. The radiosensitizing effect of 3-AB-G was determined for both cell lines. RESULTS: 3-AB-G was not toxic to cells at concentrations of 10 mmol/L or less. 3-AB-G did not alter cell survival after irradiation. CONCLUSION: 3-AB-G was not an effective radiosensitizer for the cells tested. Coupling 2 deoxyglucose to 3-AB may block the uptake of the inhibitor into the cell by altering the ability of the receptor to recognize the molecule or may interfere with the specificity of the inhibitor for poly(ADP-ribose) synthetase. PMID- 7784579 TI - Glenohumeral ligaments and shoulder capsular mechanism: evaluation with MR arthrography. AB - PURPOSE: To evaluate the efficacy of magnetic resonance (MR) arthrography in identification of the glenohumeral ligaments (GHLs) and to determine the location of abnormalities of the GHL, joint capsule, and labrum. MATERIALS AND METHODS: MR arthrograms were evaluated retrospectively in 46 patients with a history of shoulder instability, impingement syndrome, or pain of unknown cause. Imaging findings were correlated with surgical observations. RESULTS: The superior, middle, and inferior GHLs were identified on MR arthrograms in 39 (85%), 39 (85%), and 42 (91%) of the 46 patients, respectively. In diagnosis of tears of the superior, middle, and inferior GHLs, MR arthrography had a sensitivity of 100%, 89%, and 88% and a specificity of 94%, 88%, and 100%, respectively. CONCLUSION: Findings at MR arthrography can help accurate identification and demonstration of the integrity of the GHL and labrum and can help in staging of abnormalities. The large number of abnormalities depicted in the middle and inferior GHLs suggests that both might be important in the maintenance of glenohumeral joint congruity. PMID- 7784580 TI - Superficial esophageal cancer: multicenter analysis of results of definitive radiation therapy in Japan. AB - PURPOSE: To assess the effectiveness of definitive radiation therapy in patients with superficial esophageal cancer. MATERIALS AND METHODS: Method of irradiation, local control rate, survival rate, and complications were assessed in 105 patients (89 men, 16 women; age range, 50-88 years) with superficial esophageal cancer treated with definitive radiation therapy at 15 hospitals in 1981-1990. RESULTS: All lesions were confirmed to be squamous cell carcinoma. The overall 5 year survival rate was 38.7%; the 5-year disease-specific survival rate was 71.0%. The 2-year local control rate was 83.0%. Late complications occurred in 16 patients. The prevalence of complications was relatively high in the group treated with intraluminal radiation therapy. CONCLUSION: Local control and survival rates in patients treated with radiation therapy were excellent, especially in the group treated with external and intraluminal radiation therapy; however, the optimal dose and optimal combination of external and intraluminal radiation therapy should be further assessed. PMID- 7784581 TI - Definitive radiation therapy for extrahepatic bile duct carcinoma. AB - PURPOSE: To evaluate retrospectively the role of radiation therapy for extrahepatic bile duct (EHBD) carcinoma. MATERIALS AND METHODS: Twenty-seven patients with local-regional EHBD carcinomas were treated with definitive radiation therapy. Radiation therapy was delivered by means of external beam radiation therapy (EBRT) alone or combined with transcatheter iridium-192 brachytherapy. The median total dose was 54 Gy (range, 30-144 Gy). Survival rates were calculated and compared by using the log-rank test. Possible prognostic factors affecting survival were evaluated by means of univariate analysis. RESULTS: The median survival of all patients was 13 months, with 1- and 2-year actuarial survival rates of 52% and 10%, respectively. Univariate analysis revealed that men, patients with tumors limited to the bile duct, and patients receiving EBRT doses of at least 45 Gy had significantly better outcomes. Local regional recurrence was the main cause of treatment failure (82%). Two patients developed gastric outlet obstruction. CONCLUSION: Patients with locally advanced EHBD carcinomas have a low survival rate. Certain factors, however, appear to have prognostic significance. PMID- 7784582 TI - Renal perfusion in humans: MR imaging with spin tagging of arterial water. AB - The authors tested a noninvasive technique for magnetic resonance imaging of perfusion in human kidneys. Magnetic labeling (spin tagging) of aortic arterial water was performed to generate an endogenous tracer. Breath-hold renal perfusion images obtained in seven volunteers yielded average perfusion rates in cortex and medulla of 278 mL.100 g-1.min-1 +/- 55 (standard error) and 55 mL.100 g-1.min-1 +/- 25, respectively. PMID- 7784583 TI - Diseases of the bronchioles: CT and histopathologic findings. PMID- 7784585 TI - Lateral epicondylitis: correlation of MR imaging, surgical, and histopathologic findings. AB - PURPOSE: To determine the value of magnetic resonance (MR) imaging in the clinical management of chronic refractory lateral epicondylitis. MATERIALS AND METHODS: Coronal three-dimensional Fourier transform, multiplanar gradient recalled-echo, and fat-suppressed sagittal images were obtained in 33 patients. Twenty of these patients underwent surgical debridement and/or primary tendon repair and were included in the correlative study. Surgical and pathologic reports were reviewed to determine the location and gross characteristics of the tissue. RESULTS: Findings at MR imaging correlated with the surgical findings of primary degeneration of the extensor carpi radialis brevis (n = 20). Histopathologic examination demonstrated neovascularization, disruption of collagen, and mucoid degeneration without inflammation. CONCLUSION: The use of MR imaging in patients with recalcitrant lateral epicondylitis assists in surgical planning. The definition of tendon degeneration and degree of tear, as depicted on MR images, correlate well with surgical and histologic findings. PMID- 7784584 TI - Glenoid labrum: MR imaging with histologic correlation. AB - PURPOSE: To document the histopathologic basis of altered intralabral and sublabral signal intensity on magnetic resonance (MR) images. MATERIALS AND METHODS: Ten fresh cadaveric shoulder specimens underwent transaxial MR imaging with T1-weighted, proton-density-weighted, and T2-weighted spin-echo; multiplanar gradient-recalled echo (MPGR); three-dimensional Fourier transform gradient recalled echo (GRE); spoiled gradient-recalled echo (SPGR); and T1-weighted, fat suppressed sequences before and after intraarticular injection of gadolinium. Shoulders were then frozen and transversely sectioned, and histologic analysis of the labrum was performed. RESULTS: Altered intralabral signal intensity correlated with fibrovascular tissue, mucoid or eosinophilic degeneration, calcification, ossification, synovial tissue, or combinations of these findings. A sublabral transitional band of intermediate signal intensity correlated with a transitional zone of fibrocartilage. CONCLUSION: There are several causes of altered intralabral signal intensity. A transitional fibrocartilaginous zone correlates with sublabral increased signal intensity. Intraarticular administration of gadolinium improves evaluation of the glenoid labrum. PMID- 7784586 TI - Meniscal ossicle: radiographic and MR imaging findings. AB - PURPOSE: To determine the magnetic resonance (MR) imaging appearance of meniscal ossicles and correlate that with the radiographic and clinical features. MATERIALS AND METHODS: Radiographs and MR images were studied retrospectively in six patients with meniscal ossicles; all patients had intermittent discomfort in the knee, and five patients had experienced knee trauma. Imaging findings were correlated with the clinical history. Four patients underwent arthroscopy. RESULTS: All patients had a visible ossicle on conventional radiographs initially interpreted as a loose joint body. MR imaging features included a corticated marrow-containing structure within the substance of the medial meniscus near the tibial attachment that appeared as a rounded focus of increased signal intensity on T1-weighted images that decreased in signal intensity on T2-weighted images. CONCLUSION: Meniscal ossicles have a characteristic MR appearance that may help distinguish them from loose bodies. They should be considered diagnostically when a circumscribed ossification is identified near the posterior horn of the medial meniscus on radiographs. PMID- 7784587 TI - Another RSNA Malaysian journey. AB - The RSNA International Visiting Professor program gave us an opportunity to live in a different and exciting country for 6 months. We had adequate travel opportunities to visit in Southeast Asia. Most of all, the feeling of appreciation and accomplishment we received from the master students as exemplified by their concern for us made our adventure extremely rewarding. For example, on the day of departure about half the class came to the airport to bid us farewell. This gesture, as well as several farewell parties in our honor, was certainly very gratifying. I enthusiastically recommend the opportunity afforded by the RSNA Visiting Professor program, and, specifically, I am enthusiastic about the program at Universiti Malaya. PMID- 7784588 TI - Participation by radiologists and other specialists in percutaneous vascular and nonvascular interventions: findings from a seven-state database. AB - PURPOSE: To determine the relative degree of participation by radiologists and other specialists in percutaneous interventional procedures. MATERIALS AND METHODS: By using 1992 Medicare Part B claims data that covered seven states, the specialty of the physician provider was determined for all services performed within various percutaneous vascular and nonvascular interventional procedure codes. RESULTS: Radiologists' performance of interventional procedures in descending percentage of participation was as follows: renal cyst aspiration (92.7%), biliary decompression (90.5%), abdominal or retroperitoneal mass biopsy (87.7%), lung or mediastinal biopsy (84.2%), noncardiac angioplasty (76.8%), pancreatic biopsy (75.2%), upper urinary tract decompression (73.7%), liver biopsy (43.7%), renal biopsy (38.4%), certain types of abscess drainages (38.2%), and thoracentesis with tube insertion (29.4%). They had only small roles in thoracentesis for aspiration (4.7%) and tube thoracostomy (1.7%). CONCLUSION: Despite controversy between radiologists and other specialists over who should perform percutaneous interventions, radiologists have maintained strong predominance in many types of these procedures. In others, they have a shared, but still major, role. PMID- 7784590 TI - Posttraumatic arterial priapism in children: management with embolization. AB - PURPOSE: To evaluate selective embolization for management of posttraumatic priapism in preadolescent boys and color Doppler sonography for diagnosis of the causative lesion and for planning embolization. MATERIALS AND METHODS: Five preadolescent boys with posttraumatic priapism underwent selective angiography and embolization. Color Doppler sonography was performed in the last three patients. RESULTS: Selective angiography showed an intracavernosal arteriovenous fistula in two patients, pseudoaneurysm of the cavernosal artery in two patients, and asymmetric cavernosal arterial flow in the other patient. After successful embolization, detumescence was achieved in all patients. Color Doppler sonography enabled localization and characterization of the lesion causing the priapism in the three patients. CONCLUSION: Angiography with selective embolization is a safe and effective method to correct posttraumatic priapism in children. Color Doppler sonography is a valuable preangiographic study, as it allows for characterization and localization of the causative lesion and obviates diagnostic cavernosal aspiration. PMID- 7784589 TI - Intracolonic pressure measurements during hydrostatic and air contrast barium enema studies in children. AB - PURPOSE: To prospectively evaluate intraluminal pressure changes in the colon of children undergoing conventional hydrostatic (barium and water-soluble contrast material) and air contrast barium enema studies. MATERIALS AND METHODS: Dynamic intracolonic pressure was measured in 26 children undergoing hydrostatic barium (23% wt/vol) enema studies, air contrast barium enema studies, or water-soluble contrast material enema examinations. Measurements were obtained with a measuring device capable of recording rapid changes in pressure. Pressure measurements were obtained with the contrast reservoir system open (contrast material was free to run through the tubing into the patient's colon) and closed (tube was clamped). RESULTS: The colonic pressures during the filling phase with liquid contrast material were equal to those elsewhere at the same level with the hydrostatic system. Mean pressure ranged from 30 to 50 mm Hg with peaks of more than 100 mm Hg during Valsalva maneuvers. During air contrast barium enema studies, sharp pressure increases and rapid swings in the intracolonic pressure occurred during and after manual insufflation of air. CONCLUSION: During conventional hydrostatic barium enema studies, intracolonic pressures remain low. During air insufflation, there were intermittent high, sharp pressure peaks. PMID- 7784591 TI - AIDS-related lymphoma: radiologic features in pediatric patients. AB - PURPOSE: To determine the clinical, pathologic, and radiologic features in pediatric patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma and to compare these features with those in adult patients with AIDS related lymphoma. MATERIALS AND METHODS: Clinical and radiologic findings were retrospectively reviewed in nine children (aged 1-15 years) with AIDS-related lymphoma. All patients had neoplastic changes that were not consistent with hyperplastic lymphoid tissue. The children underwent ultrasonography, computed tomography, magnetic resonance imaging, and plain radiography. RESULTS: Sites of involvement by malignant non-Hodgkin lymphoma at diagnosis were the liver (n = 7), spleen (n = 5), kidney (n = 4), central nervous system (n = 2), and testis and bone (n = 1). Symptoms included seizures, respiratory distress, testicular swelling, and increased abdominal girth. CONCLUSION: Children with AIDS-related lymphoma have symptoms distinct from those found in adults, but clinical, radiologic, and pathologic findings show that almost any anatomic site in these children can be involved. PMID- 7784592 TI - Long iliac stenosis: initial clinical experience with the Cragg endoluminal graft. AB - PURPOSE: To determine the feasibility of use of a self-expanding nitinol stent covered with polyester fabric in long iliac stenoses. MATERIALS AND METHODS: In 10 patients with 12 iliac artery stenoses (6-10 cm long [mean, 7.5 cm]), a Cragg endoluminal graft was placed percutaneously after failure of percutaneous transluminal angioplasty. RESULTS: At angiography after implantation of 15 Cragg endoluminal grafts, patency was restored and the dissection flap was eliminated without any residual stenosis in all cases. At 1-13-month follow-up (mean, 7 months), eight patients were asymptomatic, with a mean ankle-brachial index of 0.90 +/- 0.15 (standard deviation). Arterial rupture occurred in one patient, with thrombosis of the artery with the stent within 1 day. In one patient, tight restenosis was seen at the proximal part of the stent. In another patient, moderate restenosis was seen at the distal junction of the prosthesis with the native artery, but restenosis did not occur within the stent. The 6-month primary patency rate of the stent graft was 80%. CONCLUSION: In long iliac artery stenoses, the deployment of the Cragg endoluminal graft is feasible and no short term complications were seen. PMID- 7784593 TI - Thrombosed hemodialysis grafts: percutaneous mechanical balloon declotting versus thrombolysis. AB - PURPOSE: To compare a technique of mechanical balloon declotting of thrombosed hemodialysis grafts with conventional pulsed-spray thrombolysis. MATERIALS AND METHODS: Forty patients had 53 episodes of graft thrombosis over a 19-month period. Twenty-nine grafts were randomly treated with thrombolysis with urokinase and 24 grafts with mechanical declotting by placement of crossed balloon catheters within the graft. Patency was determined by retrospective review of hemodialysis records. RESULTS: Successful hemodialysis for 1 week after the procedure was achieved in 21 (88%) of the 24 grafts treated mechanically and 26 (90%) of 29 grafts treated with thrombolysis. Continuous pulse oximetry showed no change in oxygen saturation in either group, and no clinical signs or symptoms of pulmonary embolism were noted. Average total procedure times were 2.2 hours for mechanical declotting and 3.5 hours for thrombolysis (P < .05). Probability of patency (mechanical vs thrombolysis) was 42% vs 45% at 3 months, 36% vs 25% at 6 months, and 8% vs 4% at 12 months. One major complication of ulnar artery embolization occurred in the thrombolysis group. CONCLUSION: Mechanical declotting of hemodialysis grafts is faster and as effective as thrombolysis. PMID- 7784594 TI - Coronary artery stenosis: detection with contrast-enhanced MR imaging in dogs. AB - PURPOSE: To monitor with fast gradient-echo magnetic resonance (MR) imaging the dynamics of gadolinium benzyloxypropionictetraacetate (gadobenate) dimeglumine on myocardial signal intensity in dogs with critical left circumflex coronary artery stenosis. MATERIALS AND METHODS: Fast gradient-echo MR images were acquired in a short axis of the left ventricle. Two bolus injections of 0.05 mmol/kg gadobenate dimeglumine were administered in the basal state after stenosis and after infusion of 0.5 mg/kg dipyridamole. RESULTS: In the basal state, there was an equivalent increase in signal intensity of normal and hypoperfused myocardium during the first pass. Dipyridamole increased left anterior descending flow (287% +/- 36; P < .05) and decreased left circumflex flow (65% +/- 14; P < .05). The magnitude of signal intensity increase during the second bolus in the hypoperfused region was less than that of normal myocardium (P < .05). Contrast enhanced images showed the hypoperfused region as smaller than the postmortem measurement (43.8% +/- 3.3; P < .05). CONCLUSION: Contrast-enhanced fast MR imaging in the vasodilated state allows detection of hypoperfused myocardium in the presence of critical coronary stenosis. PMID- 7784595 TI - Left pulmonic recess of the pericardium: findings at CT and MR imaging. AB - PURPOSE: To assess the prevalence and appearance of fluid in the left pulmonic pericardial recess (LPR) on computed tomographic (CT) scans and magnetic resonance (MR) images of patients without pericardial effusion. MATERIALS AND METHODS: Eighty consecutive contrast material-enhanced CT scans and 50 consecutive MR images of the thorax were evaluated for the presence of fluid in the LPR, transverse sinus, and superior pericardial recess. RESULTS: Fluid was identified in the LPR in approximately 25% of patients without pericardial effusion (14 of 62 CT scans, eight of 30 MR images). At MR imaging, the LPR and other recesses appeared as a signal void on spin-echo images but demonstrated high signal intensity on gradient-echo flow-sensitive images. CONCLUSION: Recognition that fluid in the LPR can be a normal finding in patients without pericardial effusion should help avert misdiagnoses of lymphadenopathy. PMID- 7784596 TI - Takayasu arteritis: evaluation of mural changes in the aorta and pulmonary artery with CT angiography. AB - PURPOSE: To evaluate mural changes in the aorta and pulmonary artery in Takayasu arteritis by using computed tomographic (CT) angiography. MATERIALS AND METHODS: CT angiography was prospectively performed in 12 women with Takayasu arteritis and in 10 healthy adults. Scanning included three distinct phases: precontrast (before administration of contrast material), arterial, and delayed. RESULTS: Precontrast transverse images revealed a high-attenuation aortic wall (10 patients) and mural calcifications in the aorta (nine patients). Arterial-phase images revealed circumferential wall thickening of 1-4 mm in all patients and enhancement in five patients with active disease. Delayed-phase CT revealed circumferential enhancement in eight patients. A concentric, low-attenuation ring was also identified inside the aorta on the arterial-phase (two patients) and delayed-phase (three patients) images. In the pulmonary artery, wall thickening was revealed with early and delayed enhancement in two patients. CONCLUSION: CT angiography may demonstrate changes in the vascular wall in patients with Takayasu arteritis. PMID- 7784597 TI - Hepatic artery resistance changes in portal vein thrombosis. AB - PURPOSE: To determine if portal vein thrombosis (PVT) is associated with changes in the hepatic artery resistive index (RI) at Doppler ultrasonography (US). MATERIALS AND METHODS: In 35 patients with findings suspicious for PVT, prospective hepatic artery RIs were obtained before angiographic proof of portal vein status. RIs were also obtained from 27 age-matched patients with liver disease (without PVT) and from eight patients with PVT (without occlusion). RESULTS: Twenty-seven of the 35 patients had proved PVT and a significantly lower (P < .01) mean hepatic artery RI than did patients in any other group studied. Twelve of these 27 patients had RI values of .50 or less, while none of the patients in any other group studied had an RI value this low (specificity, 100%). CONCLUSION: A reduction in hepatic artery RI accompanies PVT and may be a helpful secondary sign to determine this venous abnormality. PMID- 7784598 TI - Acoustic shadowing from uterine leiomyomas: sonographic-pathologic correlation. AB - PURPOSE: To investigate the origin of discrete shadowing from uterine leiomyomas at ultrasound (US) that does not progress from an echogenic origin. MATERIALS AND METHODS: Seven hysterectomy specimens with leiomyomas were scanned in a water bath. With US guidance, 13 self-retaining needles were placed at the origin of shadows that did not (12 cases) or did (one case) arise from an echogenic focus. The localized tissues were inspected for gross pathologic features and microanatomic detail. RESULTS: In the 12 cases, the shadow originated from transitional zones: the margins of the fibroid with adjacent myometrium (three needles), the edges of nodular whorls of smooth muscle (four needles), and the margin between smooth muscle bundles and hyalinized connective tissue (five needles). There was no evidence of calcification, hemorrhage, or necrosis. In the other case, microcalcifications were found. CONCLUSION: Discrete shadowing not arising from echogenic foci resulted from the structural features of the leiomyomas and occurred at transitional boundaries between juxtaposed tissue types or at the curved margins of organized anatomic structures. PMID- 7784599 TI - [Why (some) psychoanalytic therapies (must) have a long duration. Thoughts on appropriate catamnestic methods]. AB - First the author discusses some of the reasons why psychoanalytic therapy takes time, showing in the process how the psychoanalytic understanding of time is at odds with the everyday concept of it. He then makes out a case against the unthinking adoption of the psychometric procedures and evaluation techniques used hitherto in determining the success of psychotherapy. In this way certain erroneous developments in traditional psychology can be avoided in psychoanalytic catamnesis. In the concluding section the author outlines an alternative methodology of catamnesis geared to the specific epistemological requirements inherent in the process of psychoanalysis. PMID- 7784600 TI - [The individual case study as a psychoanalytic research instrument]. AB - The attacks mounted by Grawe, Donati and Bernauer on the individual case study as an instrument of research in psychoanalytic studies has had major political repercussions, not least with regard to professional corporate identity. The author takes the opportunity of inquiring into the quality and the advantages of scientific inquiry into the individual case. She proceeds in this from a discussion of the familiar quandary posed by the fact that the necessarily idiosyncratic nature of the individual case will by definition resist generalization. The very definition of inquiry that qualifies for the term "scientific" is, however, precisely that it should be able to make statements with a claim to general validity. The line taken by Leuzinger-Bohleber is that the internal (narrative) coherence of psychoanalytic interpretations should be supplemented by an external form of coherence in such a way as to ensure that genuinely psychoanalytic interpretations and concepts do not stand at odds with accepted knowledge in other scientific disciplines. With special reference to Moser's arguments, she demonstrates that a trial-and-error research approach with an inbuilt suspicion of and resistance to orthodox tenets, professions of faith and ultimate truths is quite definitely in a position to proceed from individual cases to subsequent generalizations, from data to metaphors, concepts and finally theories susceptible of validation by further new data. By referring theoretical models back to new practical situations (the therapeutic situation, the experimental situation, computer simulation) the author feels that it is entirely possible to at least sustain, if not resolve, the tension between individual case study and scientific claims of general validity. This is entirely in line with the view of psychoanalysis as a "science between the sciences", an approach reconciling "understanding" and "explanation", hermeneutics and hardcore science. PMID- 7784602 TI - [The Bern psychotherapeutic universal spirit: Klaus Graw et al]. PMID- 7784601 TI - [Klaus Grawe's confession and the psychoanalytic profession]. AB - 1994 saw the publication of the volume Psychotherapie im Wandel. Von der Konfession zur Profession ("Psychotherapy in Transition. From Confession to Profession") by K. Grawe et al. This book did much to fuel the professional policy debate on the purpose and efficiency of long-term and high-frequency analytic psychotherapies. The author examines Grawe's book, comparing its methodological approach with other (largely US-American) studies on psychotherapeutic research, and concludes that the studies analysed by Grawe do not do justice to the realities of psychoanalytic therapy. He advocates more naturalist designs reflecting the change from controlled therapies in institutions to clinical treatment in private practices. Finally he criticises psychoanalysts for having failed to provide evaluation of long-term and high frequency analysis. PMID- 7784603 TI - [Classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Genetic considerations in light of personal studies]. AB - Long-term immunogenetic studies on HLA and GLOI systems in the families of probands with classic 21-hydroxylase related adrenal hyperplasia served as a basis for a complex analysis. The analyzed factors included the phenotype and haplotype incidence, HLA-ABC homozygosity, and -in informational families-the strength of genetic linkage for recombinant fractions (lod score). The results suggest the usefulness of routine determinations of class I HLA antigens in families of patients with 21-hydroxylase deficiency. PMID- 7784604 TI - [Personal experience in clinical use of low power laser therapy]. AB - The results of our own clinical trials regarding therapeutical effects of low power lasers in the treatment of some diseases of motional system, skin and lesions of peripheral circulation were presented in the paper. The laser therapy was used in over 320 patients in period of last 3 years. The infra-red laser (wave-length 904 nm, mean power 4 mW) was used. The procedures were performed daily, for 5 days a week in 2 stages: the scan of sore region (3-min.) and the irradiation of trigger points (2-3 min. each). As a result of 10-25 procedures a significant clinical improvement in 65-90% patients was obtained. On the base of obtained results one can conclude that low-power laser therapy could make a useful supplementary method of treatment of overloading syndrome of motional system, postthrombotic syndrome, lymphatic edema and trophic lesions of skin. PMID- 7784605 TI - [Significance of myoinositol in renal physiology and pathology]. PMID- 7784606 TI - [The role of hydrochloric acid and pepsin in the etiology of peptic ulcer]. PMID- 7784607 TI - [Metformin -- biguanid of choice]. PMID- 7784608 TI - [Retinal autoimmunity]. PMID- 7784609 TI - [Intensive insulin therapy-- benefits and risks]. PMID- 7784610 TI - [All-trans-retinoic acid in the differential therapy of proliferative hemocytic diseases. I. Properties of biological retinoids]. PMID- 7784611 TI - [Inspection of work on Polish territory in the XIX century-historical features]. PMID- 7784612 TI - [Cytogenetic studies in clinical diagnosis --analysis of 1611 examination results]. AB - An analysis of the frequency and type of chromosome aberrations found in 1611 cytogenetic studies has been done in relation to the clinical indications. The most frequent reason for referral was: MCM/MR syndrome (15.4% cases), suspicion of sex chromosome abnormality (13.1%), Down syndrome (11.2%) and reproductive wastage (10.6%). The incidence of abnormal karyotypes in these groups of patients was 10.1%, 24.2%, 87.9% and 9.3% per couple, respectively. The lowest percentage of chromosome aberrations was found among patients with nonspecific mental retardation (2.2%) and in the families who lost a baby with MCM Syndrome (3.3% per couple). On the whole, abnormal karyotype was found in 364 patients (22.6%). Among 62 families identified by the affected child with, structural chromosome aberration in 24 families (38.7%) the abnormality was familial in the origin. PMID- 7784613 TI - [Respiratory infections in the surgical intensive care unit]. AB - The purpose of the study was to assess microbiological structure and the influence of the predisposing factors on frequency of lower respiratory tract infections. The study group consisted of 72 patients admitted to the Intensive Care Unit between January and October 1994. We found that 27 pts. (39%) developed respiratory infections. The risk of an infection was much higher in the group with long (over 5 days) stay on ICU, which required artificial ventilation as well as in the group of patients treated due to acute pancreatitis. More than 75% of isolated strains were Gram negative bacteria. Using susceptibility tests we conclude that Pseudomonas aeruginosa, Serratia, and Acinetobacter baumanii are highly resistant to antibiotics. The results suggests that 3rd generation cephalosporins and imipenem are most efficient in vitro. PMID- 7784614 TI - [Prognostic significance of some clinical and laboratory parameters in patients with chronic myelogenous leukemia]. AB - The correlations between select clinical and laboratory data recorded at the time of diagnosis in 125 chronic myelogenous leukemia patients (60 men and 65 women) and survival time these patient was analysed. All patients were treated with similar methods. Characteristics for which there was evidence of associations with shorter survival outcome were older age, anemia, high percentage of peripheral and marrow blasts and thrombocytopenia or thrombocytosis. There was no evidence of statistically significant prognostic value such parameters as: sex, presence of symptoms, hepatosplenomegaly, high leukocytosis (WBC), high proportion of circulating promyelocytes, neutrophils and eosinophils and serum LDH or leukocyte alkaline phosphatase activity. Peripheral basophilia appeared to have advantage prognostic relevance to survival time. The median survival time observed patients was 38-65 months. PMID- 7784615 TI - [Hepatitis B (HBV) and C (HCV) virus infections as an eventual cause of chronic hepatic damage in patients undergoing maintenance hemodialysis ]. AB - In 67 hemodialysis patients with high prevalence of HBV infection (64/67-95.5%) the occurrence of anti-HCV antibodies in second generation enzyme immunoassay was 61.2% (41/67). Among 40/67 (59.7%) patients with actually or previously detected biochemical signs of chronic hepatic injury the H Bs antigen or/and/anti-HCV antibodies were positive in 38 (95.0%) cases. High prevalence of HBV and HCV infections in studied population and their connection with biochemical signs of chronic hepatic injury shows the necessity of introduction the intensive prophylaxis of those infections in polish hemodialysis centers. PMID- 7784616 TI - [The value of serum CA 125 for monitoring treatment of patients with ovarian cancer]. AB - To evaluate the value of serum CA 125 antigen in monitoring of treatment of ovarian carcinoma, serum levels of this marker were monthly assayed during treatment and follow-up period in a group of 112 patients. CA 125 levels decreased in all 67 patients with remission. In a group of 41 patients with progressive disease, in 38 (93%) CA 125 levels increased, and in 3 (7%) - remained elevated. CA 125 became negative in all patients with clinical complete remission, although in 14 (38%) patients in this group second-look laparotomy revealed microscopic disease. In 12 of 15 patients with complete pathologic remission the increase of CA 125 preceded (2 to 58 weeks, median - 12 weeks) the recurrence of the disease. Time to progression depended on the increase rate of the antigen level. PMID- 7784618 TI - [Use of alprazolam in treatment of mental disorders]. PMID- 7784617 TI - [Postoperative complications after intestinal bypass operations for extreme obesity]. PMID- 7784619 TI - [The role of selenium in the metabolism of thyroid hormones]. PMID- 7784620 TI - [Non-typical tumor of the left kidney]. AB - The paper presents the diagnosis and treatment of 62-years old male, admitted to the hospital with supposition of splenomegaly. X-ray of abdomen and urography showed in the location of left kidney irregularly calcified tumor with features of a huge mould concretion in the collecting system of the left kidney. After subsequent diagnostic procedures as: ultrasonography of abdomen, aortonephrography, CT, patient was qualified for surgical intervention. A large tumor (10 cm in diameter) with calcified walls, in part infiltrating mesenterium of large intestine suggesting neoplastic infiltration, was removed from extraperitoneal area. Histopathological examination identified the tumor as a defunct kidney filled with caseous masses, separated from the remains of kidney with calcified wall. No active tuberculosis was found in examined sections. The paper presents the problems in differential diagnosis of tumors localised in left hypochondrium. PMID- 7784621 TI - [Electrolyte disturbance and hyperglycemia in villous adenoma of the sigmoid colon-case report]. PMID- 7784622 TI - [Inspiration for initiation of collections in the Medical Department Museum of the Jagellonian University]. PMID- 7784623 TI - A novel application of a competitive binding model in dioxin risk assessment. AB - The EPA-recommended toxicity equivalence factor (TEF) approach to estimating the lifetime incremental cancer risks for dioxins does not address (a) differences in the severity of toxicity according to the composition of chemical mixture and (b) potentials for modification of tissue-level doses of congeners in mixtures and consequently the cancer risk estimates. Our earlier efforts to model the binding of congeners to the Ah receptor in the low-dose range and to develop quantitative estimates for the formation of fractions of Ah receptor-congener complexes resulted in the definition of a unique parameter, defined as competitive binding ratio (CBR), to adjust tissue-level doses for mixture exposure. We made an effort to incorporate CBR values in the dose-response analysis and risk characterization of congeners in two distinct exposure scenarios. The modified approach to estimating tissue-level doses of congeners in mixtures by the use of a competitive binding model indicated that (a) the Ah receptor affinity is an important criterion in the determination of tissue-level dose of congeners, (b) the TEF doses calculated by using the model algorithms modified the tissue-level doses for congeners in mixture exposures, and (c) the combined lifetime incremental cancer risks for all congeners were generally lower when model algorithms were used in the dose-response analysis. However, the percentage contribution of toxic congeners was significantly higher when model algorithms were used. The percentage contribution of higher congeners with low toxicity was considerably reduced when model algorithms were used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784624 TI - Evaluation of ambient asbestos concentrations in buildings following the Loma Prieta earthquake. AB - On October 17, 1989, an earthquake struck central, coastal California including San Francisco and the Bay Area, damaging many buildings. Because of concern over the possible exposure to asbestos in the damaged buildings, building owners/managers hired several Bay Area industrial hygiene firms to collect air samples in suspect buildings. RJ Lee Group analyzed a total of 419 air samples from 55 buildings (25 school, 3 university, 20 commercial, 5 public, and 2 residential buildings) using transmission electron microscopy and has compiled the results. The data from each building were averaged and grouped accordingly into three classifications: indoor buildings, buildings with asbestos abatement in progress at the time of the earthquake, and buildings where sampling was performed to monitor clean-up of debris. Several buildings were sampled on more than 1 day. The results indicate that asbestos levels differed little from outdoor levels, even immediately after the earthquake. Exceptions to this were samples collected in the vicinity of debris clean-up and in buildings undergoing abatement which were higher than the indoor or outdoor samples. However, these samples generally had concentrations below the AHERA clearance levels and all were well below the OSHA action limit. PMID- 7784625 TI - Lung particle overload: implications for occupational exposures to particles. AB - Chronic pulmonary inflammation, pulmonary fibrosis, and even lung tumors developed in a number of chronic inhalation studies in rats with highly insoluble nonfibrous particles of low cytotoxicity. Concerns were expressed that these responses are due to excessive particulate lung burdens, and the term "particle overload" was coined to characterize these conditions. The hallmark of the particle-overloaded lung is an impairment of alveolar macrophage (AM)-mediated lung clearance which has been demonstrated in all species tested so far and which eventually leads to accumulation of excessive lung burdens. Experimental evidence suggests that the volume of the particles phagocytized by AM is most critical for causing their impaired clearance function, and that the condition of lung overload is reached once the retained lung particle burden reaches a level equivalent to a volume of approximately 1 microliter/g of lung. Cytotoxic particles also cause impaired AM clearance function, yet at a much lower lung burden which does not qualify as particle overload. Significant species differences exist with respect to the induction of adverse chronic effects in response to lung overload; i.e., mice and hamsters are less prone to developing chronic inflammation and pulmonary fibrosis, and lung tumors have been observed only in rat studies. Lung tumors or fibrosis in the rats were seen only at lung burdens having caused impaired particle clearance, and a threshold dose for the adverse chronic effects can be postulated which is defined by a lung particle burden not causing impairment of clearance. Thus, the lung tumors observed in chronic rat studies at very high particulate exposure concentrations may not be relevant for human extrapolation to low-exposure concentrations. Evidence in humans suggests that particle-overloaded lungs, e.g., in coal workers, respond with fibrosis, but no increased incidence of lung tumors has been found in this group. However, it cannot be excluded that other types of chronically inhaled particles may have a carcinogenic potential in the human lung if accumulating to very high lung burdens. More research is needed for a detailed understanding of the basic mechanism leading to nonfibrous particle-induced tumorigenesis in the lungs of different species. Altered particle accumulation and retention kinetics and chronic inflammation in the overloaded lung indicate that the maximum tolerated dose (MTD) has been exceeded. No specific guidelines for inhalation studies defining the MTD have been established; general guidelines are not necessarily applicable for chronic inhalation studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7784626 TI - Human exposure to polychlorinated biphenyls (PCBs): a critical assessment of the evidence for adverse health effects. AB - Results from epidemiologic studies involving human exposures to polychlorinated biphenyls (PCBs) are often used to estimate the potential risk or hazard posed by the presence of these chemicals in the workplace or the environment. The use of results and conclusions from individual studies requires an assessment of the scientific quality of the information contained in published reports. The results of a critical review of the scientific literature reported here should be an aid to those who are interested in risk evaluations surrounding exposures to PCBs. There are diverse approaches that one could take to an evaluation of scientific reports of the health hazards of various chemicals. We present one approach to assessing the strengths and weaknesses of studies conducted to understand the potential association between PCB exposure and human health effects. A comprehensive review of the scientific literature involving human exposures to PCBs was performed and each study was evaluated on the basis of a defined set of criteria that were considered standards in epidemiologic research. Two of the 39 occupational studies reviewed provided positive evidence and 3 suggestive evidence for an exposure-related effect, whereas none of the 33 studies where exposure had occurred in the natural environment provided positive or suggestive evidence of an association with adverse effects. PMID- 7784628 TI - Copper guideline values for drinking water: reviews in need of review? PMID- 7784627 TI - Analysis of studies related to tumorigenicity induced by hydroquinone. AB - Hydroquinone (HQ) produced renal adenomas in male F344 rats, and these tumors appeared to arise from areas of spontaneous progressive nephropathy; the nephropathy itself has been found to be enhanced by HQ. Other neoplasms were not confirmed to be causally related to HQ among the reported bioassays. In the male F344 rat, HQ administered alone was not DNA reactive. HQ produced enhanced proliferation of renal tubular epithelium, presumably through toxicity involving glutathione conjugate formation. In the kidney, bone marrow, and other tissues, HQ may induce toxicity by redox cycling and lipid peroxidation. In bone marrow, HQ may produce microtubulin dysfunction, which is a plausible explanation for positive cytogenetic tests, the only consistently positive genotoxicity effect reported for HQ. Although HQ is a metabolic product of benzene, several lines of evidence suggest that the effects of HQ exposure are significantly different from those of benzene. Based upon the plausible mechanisms by which HQ may produce kidney tumors in male rats, we have concluded that occupational exposure levels of HQ are not predicted to be a cancer risk for humans. PMID- 7784629 TI - Ischemic heart disease and spousal smoking in the National Mortality Followback Survey. AB - Data on never-smoking decedents from the 1986 National Mortality Followback Survey were used to perform a case-control analysis of ischemic heart disease in relation to spousal cigarette smoking. The case groups consisted of 475 men and 914 women who died from heart disease. Controls consisted of 998 men and 1930 women who died from other causes. In this study there was no association between spousal smoking and ischemic heart disease in either sex (males, odds ratio = 0.97; females, odds ratio = 0.99). The results of this study are in striking disagreement with risk elevations reported in several previous studies of spousal smoking and heart disease. PMID- 7784631 TI - Short communication: selecting input distributions for use in Monte Carlo simulations. AB - Monte Carlo analysis is increasingly employed as a means of quantifying uncertainties in risk assessment. However, the output of any Monte Carlo analysis is extremely sensitive to the input distributions used. In this paper we present a simple set of guidelines for the selection of input distributions. The guidelines involve allocating variables with unknown distributions to appropriate distributional "classes," based on the range of possible values that could be obtained for the data and known characteristics about the behavior of the variable. If the class of distribution is not identifiable, then variables can be related to a specific distribution using goodness-of-fit techniques. If these identification schemes fail, bootstrapping techniques may be used to generate a sampled distribution from the available data. Finally, "default" distributions may be employed using analogous data if site-specific data are unavailable. PMID- 7784630 TI - Publication bias in the environmental tobacco smoke/coronary heart disease epidemiologic literature. AB - Two approaches are used to assess publication bias in the environmental tobacco smoke/coronary heart disease (ETS/CHD) literature: (1) Statistical tests applied to all sex-specific relative risk (rr) estimates from 14 previously published studies indicate that publication bias is likely. A funnel graph of the studies' log relative risks plotted against their standard errors is asymmetrical, and weighted regression of the studies' log relative risks on their standard errors is significant (P < 0.01). (2) Previously unpublished ETS/CHD relative risks from the American Cancer Society's Cancer Prevention Studies (CPS-I and CPS-II) and the National Mortality Followback Survey (NMFS) do not show an increased CHD risk associated with ETS exposure. CPS-I: men, rr = 0.97 (0.90-1.05); CPS-I: women, rr = 1.03 (0.98-1.08); CPS-II: men, rr = 0.97 (0.87-1.08); CPS-II: women, rr = 1.00, (0.88-1.14); NMFS: men, rr = 0.97 (0.73-1.28); women, rr = 0.99 (0.84-1.16). Comparison of pooled relative risk estimates from 14 previously published studies (rr = 1.29; 1.18-1.41) and unpublished results from three studies (rr = 1.00; 0.97-1.04) also indicates that published data overestimate the association of spousal smoking and CHD (chi 2 = 25.1; P < 0.0001). PMID- 7784632 TI - A reexamination of recent publications suggesting o-toluidine may be a human bladder carcinogen. PMID- 7784633 TI - Integrated approach for environmental assessment of new and existing substances. AB - To ensure the environmental safety of new and existing substances, the environmental fate and potential effects resulting from their release into the environment must be assessed. This requires the development of reasonable, consistent, and effective methods to conduct environmental risk assessments and to prioritize testing for these substances. This assessment must integrate fate and effects at the point-of-entry; it should also extend to an assessment of the potential to persist, and the consequences of increases in exposure concentrations, and to bioaccumulate. The conventional environmental risk assessment approach is used to assess the fate and effects of a substance at its point-of-entry into the environment. In this paper, an approach is presented for conducting quantitative environmental risk assessments of new and existing substances that builds on this conventional approach by including quantitative assessment of the potential for, and consequences of, persistence and bioaccumulation. The approach is described for aquatic, sediment, and terrestrial environments. For each environmental compartment, the approach includes (i) classification of the substance, based on environmental partitioning processes, to ensure that the appropriate data are collected and models used; (ii) a fate assessment to understand the ultimate fate of the substance after entry into the environment or "an environmental compartment" and to predict the exposure concentration of the substance at point-of-entry; (iii) a persistence assessment which determines the potential for increase in the exposure concentration as a result of repeated additions of the substance; (iv) effects assessment; (v) environmental risk assessment to examine the potential for adverse impact on ecosystems; and (vi) a bioaccumulation assessment to evaluate the potential for direct and indirect effects on the species of interest due to bioaccumulation. The assessment approach is illustrated using data for a hypothetical consumer product substance that is disposed down-the-drain. PMID- 7784634 TI - Historical review of the rodent bioassay and future directions. PMID- 7784635 TI - Bioassay design and MTD setting: old methods and new approaches. AB - The proper design of carcinogenicity bioassays is critical to the interpretation and use of the data that emerge upon its completion. This paper explores some of the scientific underpinnings that need to be considered when designing bioassays. It also discusses new approaches that can be used to improve dose setting and interpretation of bioassay results. Critical information that determines the shape of the dose-response curve include the molecular dose of the agent that binds to DNA, cell proliferation, and cell death. Such data can be used to replace default assumptions and improve the extrapolation of risk from animal studies to humans. PMID- 7784636 TI - Data analysis: statistical analysis and use of historical control data. AB - Survival-adjusted methods for the statistical analysis of tumor data from long term rodent carcinogenicity studies are described. Although most of these methods require knowledge of whether individual tumors are "fatal" or "incidental," such determinations may be difficult. Several methods for dealing with this and with other data analysis issues are discussed. Historical control tumor data may be useful in the interpretation of rodent carcinogenicity studies, particularly for rare tumors and for borderline effects. Although statistical methods are available for using historical control data in a formal testing framework, the primary difficulty is establishing a database that is truly comparable to the study under evaluation with respect to those factors known to influence tumor occurrence. Major sources of variability in tumor incidence include the animal room environment, dietary factors/body weight, gross necropsy and slide preparation procedures, and histopathology diagnosis. The National Toxicology Program's use of historical control data is briefly described and illustrated. PMID- 7784637 TI - Modulators of carcinogenesis. AB - For decades, it has been known that a number of different factors (e.g., species, metabolism, age, animal husbandry, diet) may exhibit a significant modulating effect on the process of carcinogenesis. Often, however, these modulators have been largely uncontrolled and thus have made uncertain the results of many carcinogenicity bioassays. Fortunately, current research into molecular carcinogenesis is beginning to provide methods, not only to understand the molecular basis of known modulators of carcinogenesis, previously described only in empirical terms, but also to allow genetic modulation of carcinogenesis in experimental systems. An expanding body of knowledge regarding the role of oncogenes and tumor suppressor genes in neoplastic events is leading to a better understanding of carcinogenic mechanisms and points to the use of transgenic animal species in carcinogenicity bioassays. The transgenic animal provides methods to examine the molecular basis of carcinogenesis in experimental systems in addition to enhancing the sensitivity of carcinogen identification and the biological specificity of chemical risk extrapolation. PMID- 7784638 TI - Regulatory aspects of carcinogenicity studies and the Delaney clause. PMID- 7784639 TI - Human relevance of animal carcinogenicity studies. AB - Extrapolation of results from rodent bioassays involving high-dose exposures to possible carcinogenic risk in humans exposed to low doses is based on the assumptions of species relevance and high- to low-dose extrapolation. For genotoxic chemicals, such as 2-acetylaminofluorene and N-[4-(5-nitro-2-furyl)-2 thiazolyl]formamide, these assumptions appear to be appropriate, although the dose response can be greatly modified by cell proliferation effects of these chemicals at high doses. In contrast, nongenotoxic chemicals, such as chemicals causing urinary calculi or sodium saccharin and related sodium and potassium salts, frequently are carcinogenic only at high doses and/or only in specific species. Consequently, for extrapolation of results for nongenotoxic chemicals these assumptions may not be appropriate. PMID- 7784640 TI - Benzoyl peroxide: an integrated human safety assessment for carcinogenicity. AB - Topical benzoyl peroxide has been used in the treatment of acne for over 30 years, with no reports of adverse effects that could be related to skin carcinogenesis. Two case-control epidemiological studies have found a lack of association between the specific use of benzoyl peroxide and skin cancer. In addition to these findings in humans, 23 carcinogenicity studies in rodents with benzoyl peroxide, including 16 employing topical application, have yielded negative results. An increase in skin carcinomas was reported in 1 study in which benzoyl peroxide in acetone was applied to the skin of SENCAR mice for a 1-year period; however, this study did not employ adequate control groups to fully understand the unusual findings, and the results were inconsistent with those of 6 other similar studies. While benzoyl peroxide is not a complete carcinogen in animals and has weak or no mutagenic potential, it has been found to be a tumor promoter in mouse skin using experimental two-stage models of carcinogenesis. Consistently positive results have been obtained in tumor promotion studies in which SENCAR mice were exposed to initiating doses of potent experimental carcinogens followed by promotion with benzoyl peroxide in acetone. Negative results have been obtained in similar studies with commercial formulations. However, the results of promotion studies with benzoyl peroxide do not carry significant weight for human safety assessment as evidenced by (i) the absence of demonstrated carcinogenicity in humans of a number of rodent tumor promoters despite long-term human exposure; (ii) the observation that tumor promotion in mouse skin occurs only under specific experimental conditions and predominantly in highly sensitive strains; (iii) clinical use scenarios markedly different from the conditions resulting in tumor promotion in mouse skin; and (iv) the significant physiological differences between mouse and human skin. Thus, to date, available scientific evidence does not allow the results of these rodent promotion studies to be meaningfully applied to human safety assessment. As such, significant scientific progress must be made before human safety estimations can be derived from rodent promotion data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7784641 TI - [Dynamic anterior jerk of the shoulder. A new clinical test for shoulder instability. Preliminary study]. AB - PURPOSE OF STUDY: A new clinical test named "The shoulder anterior jerk test" is proposed to confirm the diagnosis of chronic shoulder anterior instability. MATERIAL: The test combines of a compression force and a translation force, applied along the arm between the humeral head and the glenoid cavity. In so doing, a subluxation of the humeral head is provoked and it is accompanied with a jerk recognised by the patient as his instability. METHODS: Three different populations of patients had been studied: Population A: 28 patients operated on for chronic anterior dislocation, uni or bilateral (32 shoulders), had been tested before the operation, without and under anesthesia. Population B: 100 patients without any problem at the shoulder, had been tested before and under anesthesia done for knee or hip surgery. Population C: 100 young sportive athletes with normal shoulder tested without anesthesia. RESULTS: Population A: The 28 patients suffering from shoulder instability had all a positive shoulder jerk test under anesthesia. Without anesthesia the test had been positive only in 10 cases (30 per cent). The jerk is potentially present for all the patients, but it is disturbed by apprehension. Population B: Among the 200 shoulders tested, 26 shoulders (17 patients) had a positive test under anesthesia (13 per cent). 5 had positive jerk test without anesthesia. Population C: 5 among the 200 shoulders tested had a positive jerk test (2.5 per cent) Under anesthesia the test has a sensitivity of 100 per cent, a specificity of 87 per cent, a positive predictive value of 55 per cent and a negative value of 100 per cent. Without anesthesia, the test has a sensitivity of 31 per cent, a specificity of 97.5 per cent, a positive predictive value of 66 per cent and a negative predictive value of 90 per cent. DISCUSSION: The instability which is shown by the jerk test is in relation with the anterior subluxation of the humeral head in front of the anterior edge of the glenoid cavity. It reproducts, with a minimal amplitude, the clinical instability which is recognized by the patient. The test is always positive under anesthesia in case of chronic anterior instability, it may confirm pre-operative diagnosis just before the begining of the procedure and may orientate the choice of it. Apprehension is a major obstacle to the research of the jerk, but it is the same with the other classical clinical tests of the shoulder anterior instability. CONCLUSION: The anterior jerk test of the shoulder is thus a test which is able to prove the diagnosis of an anterior instability. The future will permit to confirm its efficiency and will confirm if the test may differenciate anterior and inferior instability with variation of the abduction, as it has been shown in this preliminary study. PMID- 7784642 TI - [Long-term result of lumbar disk chemonucleolysis (a 8-12 years follow-up)]. AB - INTRODUCTION: This study is an attempt to assess the effects of chemonucleolysis over an extended period of time (8 to 12 years follow-up). MATERIAL AND METHODS: From 1981 to 1985, chemonucleolysis using Chymopapain was performed on 134 patients for the relief of radicular pain from herniated lumbar discs. The long term results were evaluated in 110 patients. This represented a total follow-up rate of 82 per cent. 24 patients were lost to follow-up. RESULTS: Of the 110 patients who had been reviewed at 8 to 12 years follow-up: 76 patients did not need other treatment than the initial chemonucleolysis. The results were excellent or good in 69 patients (63 per cent) and fair in 7 patients (6 per cent). 34 required surgery (31 per cent). This rate does not reflect the real failure rate of chemonucleolysis: 7 patients underwent early surgery and corresponded with the beginning of our experience with chemonucleolysis. 7 patients needed surgical treatment after a successful initial result for two to nine years. The real failure rate concerned 19 patients (17 per cent). These patients did not have any pain relief following chemonucleolysis. Surgical treatment was undertaken on the average 18 months after chemonucleolysis. One patient had suffered from radicular pain 6 years following the first chemonucleolysis. In this case, iterative chemonucleolysis had been done on the same lumbar level. It was effective on the radicular pain but not on the back pain. Chemonucleolysis had been effective in 70 per cent of the patients. DISCUSSION: Our study showed that the long term results following chemonucleolysis were effective and the mortality rate was low. (No severe complication in this study). This study is compared with the literature, studying the results of chemonucleolysis patients, or comparing patients treated by chymopapain or surgical discectomy. CONCLUSION: We conclude that chemonucleolysis is an effective and safe method for treating sciatica by herniated lumbar discs. PMID- 7784643 TI - [Letournel's ilio-femoral way in acetabular fractures of the two columns. A prospective study]. AB - PURPOSE OF THE STUDY: The authors present the anatomical and functional results of the systematic use of Letournel's extensive lateral approach for internal fixation of the fractures of the acetabulum involving the two columns. MATERIAL: This prospective study concerns 25 patients. Mean age was 38 years. Mean follow up was 4 years and 6 months (with extremes of 1 year and 9 years 9 months). 13 cases had a minimum of 4 years of follow-up. There were 1 transversal fracture, 9 transversal fractures associated with a posterior wall fracture, 2 anterior column fractures associated with a hemitransversal posterior fracture, 6 "T" shaped fractures, 7 fractures of the two columns. During the procedure, a trochanterotomy was carried out. Not any of the patients was irradiated postoperatively and they did not take any indomethacin. The patients were operated on 10 days after the accident, on average (with the extremes of 2 and 60 days). The average time of the procedure was 4 H 20 and 1080 cc of globular sediment were used during the intervention on average. The same surgeons participated in each operation. METHODS: The anatomical results were analysed according to Matta's criteria and the congruence study head-roof and head acetabulum of the SOFCOT symposium in 1981. The functional results were analysed using the quotation of Merle d'Aubigne. Complications were searched systematically. The appearance of heterotopic ossifications was analysed according to Brooker. RESULTS: 23 patients had a satisfactory anatomical reduction and 11 patients out of 13 did not present any arthrosis after a minimum of 4 years follow-up. 12 patients had very good or good functional results. 3 patients had no heterotopic ossifications, 7 were grade I, 5 grade II, 8 grade III, and 2 grade IV. The gluteus medius was quoted 4 in 18 patients and 5 in 5 patients. There were 2 cases of deep suppuration, one of them was a patient who died 6 months later of a pancreas cancer unrecognized at the time of the accident. There were 5 aseptic osteonecroses and 3 cases of regressive paralysis of the sciatic nerve. 4 total hip prosthesis were inserted secondarily. DISCUSSION: The Letournel extensive lateral approach was efficient to obtain an anatomical reduction but, functionally, it was only efficient in one case out of two. For the moment, the authors associate systematically a postoperative irradiation to reduce the ossifications (10 to 12 gray in 5 sessions). On the other hand, they try to obtain a more efficient reinsertion of the glutei muscles, thank to a bone fragment of the iliac crest. CONCLUSION: The authors limit their indications of the Letournel's extensive lateral approach to the fractures of the two columns, not older than 10 days or to the comminuted ones. PMID- 7784645 TI - [Prosthetic replacement for pathological fractures of the proximal end of the femur: total prosthesis or bipolar arthroplasty?]. AB - INTRODUCTION: The purpose of this prospective study was to present our experience with bipolar or total hip arthroplasty in 28 consecutive cases of metastasis of the intertrochanteric and subtrochanteric area. MATERIALS AND METHODS: Twenty eight patients with metastatic involvement of the proximal femur underwent either bipolar or total hip arthroplasty. Proximal femoral resection and prosthetic replacement with a massive component was routinely performed. RESULTS: The postoperative morbidity rates for dislocation and pressure sores were significantly lower (p < 0.05) in the bipolar arthroplasty group. Postoperative pain relief according to Habermann was excellent in 81.5 per cent and good in 14.8 per cent of the patients. The functional results according to the hip rating scale of Merle d'Aubigne were rated as excellent in 19 per cent, very good in 22 per cent and good in 22 per cent of the hips. The prognosis for survival was superior in patients with a preoperative Karnofsky performance status index of more than 60 points (p < 0.01) and in patients without postoperative pulmonary complications (p < 0.01). New bone formation around the femoral prosthetic component occurred in 11 (61 per cent) of the 18 patients surviving three months or longer. This bone formation did not affect the clinical results. In the current series pain relief as well as postoperative walking ability were comparable in both groups but the dislocation rate was significantly lower (p < 0.05) with bipolar arthroplasty. CONCLUSION: We recommend bipolar arthroplasty rather than total hip arthroplasty in patients with a preoperative Karnofsky performance status index of more than 60 points if bone disease of the acetabulum is not evident on standard radiographs and if during operation the acetabular cartilage appears normal. PMID- 7784644 TI - [Femoral osteotomy for severe hip osteoarthritis: an actuarial analysis of results]. AB - INTRODUCTION: In cases of severe hip osteoarthritis in young patients, the intertrochanteric osteotomy can delay total hip arthroplasty. The main advantage of the osteotomy is to preserve the bone stock. The main disadvantages are the lasting postoperative invalidity and the varying longterm success rate. Our aim was to quantify these disadvantages using survivorship analysis. MATERIAL AND METHODS: The study included 64 patients (65 osteotomies) ranging from 16 to 68 years. The osteotomies were performed between 1975 and 1987. The osteoarthritis was stage III or IV, with a joint space less than 50 per cent. Osteoarthritis was primitive in 25 cases and secondary in the others. The osteotomy always included a medial displacement of the shaft according to the principle of Mac Murray's procedure, but also 22 cases (33.8 per cent) had a varus angulation and 19 (29.2 per cent) a valgus angulation. The preoperative pain score according to the Merle d'Aubigne (MDA) grading was 2.6 (1 to 4) and the global functional score was 11.1 (5 to 15). The patients were reviewed in 1991 and examined clinically and radiographically. RESULTS: The results of the 65 cases were distributed into 3 groups: -29 cases having reached the follow-up without difficulty, -7 patients were lost for follow-up examination, 6 of these latter than 9 years, -29 patients taking osteotomy failure as a pain lesser than the 3 MDA score. The postoperative delay to obtain the best functional result was 6 to 24 months (mean: 13.65). This result ranged from 5 to 17 MDA score (mean: 15) with pain ranging from 2 to 6 (mean: 5). The survivorship analysis curve showed 67.5 +/- 19.5 per cent survival for all osteotomies to the interval of 9-10 years. There were 3 types of results: -3 early failures (4.6 per cent) one because of a deep infection, -in 7 cases, after a short initial functional improvement, there was a progressive degradation leading to failure in 3.7 years (2 to 6 years), -55 cases with a lasting period of functional improvement, 26 osteotomies leading to failure in 3.5 to 15 postoperative years and, 29 cases having reached the follow-up (7 to 16 years mean 10 years). There was radiographic improvement of the osteoarthritis increasing the joint space in 59 cases (90.7 per cent). There was no radiographic improvement in the 6 other cases, including the 2 functional failures. The functional degradation appeared parallel to the radiographic degradation leading to a decrease of joint space to 90 per cent. We tested differences between various groups using Log Rank test. We found no difference in survival between the 3 different types of osteotomy. DISCUSSION: The results of this study can help to choose between intertrochanteric osteotomy and THA in the case of severe osteoarthritis. The best functional result of the osteotomy is in one postoperative year, with a mean MDA score of 15 and a mean pain score of 5. It appears that we do not predict the duration of functional improvement, the patient has 2/3 chances that this improvement reaches 10 years. PMID- 7784646 TI - [Femoral neck fractures: position of the implant, unrecognized articular penetration and its consequences]. AB - INTRODUCTION: Only two dimensions of a three dimensional object are visible on plain roentgenograms. Therefore, on gross inspection of antero-posterior and lateral roentgenograms, a screw may project as being safely within the head of the femur even though penetration has occurred. This region may be referred to as a "blind zone". MATERIAL AND METHODS: Unrecognized screw penetration into the hip joint during internal fixation of femoral neck fractures was researched on intra operative roentgenograms of 30 patients. Unrecognized pin penetration through the posterior part of the neck was also analyzed on the same X Rays. RESULTS: Unrecognized screw penetration into the hip joint was observed in 20 per cent and penetration at the posterior part of the neck was observed in 10 per cent of cases. DISCUSSION: Several methods of determining screw position are described and discussed in this study. PMID- 7784647 TI - [Hollow femoral trochlea and femoro-patellar osteoarthritis]. AB - INTRODUCTION: The high frequency of femoro-patellar syndrome encountered in Libreville (Gabon) and its association with shallow trochlea and important cartilaginous lesions in our surgical cases urged us to investigate the role of this dysplasia as a cause of femoro-patellar osteoarthritis. MATERIAL AND METHODS: Our study consisted of two series: a retrospective study: 50 patients operated for complications of femoro-patellar syndrome. a prospective study: we analysed the trochlea morphology of 100 healthy Gabonese. RESULTS: In our operated cases, we noted a high frequency of shallow trochlea (61 per cent) with important cartilaginous lesions (64 per cent of femoro-patellar osteoarthritis). In the prospective study, we noted 89 per cent of shallow trochlea. The average trochlea angle was 126 degrees. DISCUSSION: The review of the operated patients showed important cartilaginous lesions associated with a "closed angle trochlea", confirming the observations of Buard and coll., and showing that this dysplasia can be a cause of femoro-patellar osteoarthritis. The prospective study found 89 per cent of shallow trochlea, which is higher to that seen in Europe (19 per cent for Buard and Coll.) and may pose the problem of an anatomic predisposition of osteoarthritis in the Central African patients. CONCLUSION: The shallow trochlea is a dysplasia often encountered in Central Africa. It is associated with important cartilaginous lesions. The shallow trochlea seems to be a favourable factor to femoro-patellar osteoarthritis. PMID- 7784648 TI - [Posterior luxation of the tibia on total knee prosthesis: apropos of 6 cases]. AB - PURPOSE OF THE STUDY: Posterior dislocation of Total knee arthroplasty is an infrequent but serious complication. Six cases of this complication were treated from 1979 to december 1993, all occurring on primary arthroplasties. MATERIAL AND METHODS: Knee arthroplasty was performed once for rheumatoid arthritis, five times for osteoarthritis. All cases occurred with a semi constrained prosthesis sacrifying posterior cruciate ligament: 2 Total condylar without posterior stabilisation, and 4 posterior stabilised prosthesis. In one case the dislocation occurred on a very severe rheumatoid arthritis: the patient, confined in a wheel chair, was not reoperated. In two patients, the dislocation was due to rotatory malposition of the tibial component. In the last three cases, we did not found any cause to the dislocation, except ligament laxity: 2 of these patients had, pre operatively, a valgus deformity. In 6 cases, we found only 2 problems on extensor system (one patellar dislocation and one patellectomy). RESULTS: 5 patients required a surgical treatment In 2 cases, we used a more constrained prosthesis, with poor results, but the knee was stable. Once, by changing the position of the tibial component, and using a thicker plate. In 2 patients we only put a thicker tibial polyethylene component. These 3 patients had a good stability: 2 have an excellent result with H.S.S. rating system, the third one has a poor result explained by patellar pseudoarthrosis occurring after traumatic patellar fracture. DISCUSSION: With our patients and cases published in North American works, we have studied the different mechanisms of such a posterior dislocation: rotatory disorder on tibial component, ligament laxity in flexion, extensor system deficiency, valgus deformity with important postero lateral release. CONCLUSION: The causes of posterior dislocation on Total knee arthroplasties must be known: we have to try to prevent such a complication. If it occurs, a precise analysis will permit a logical curative treatment, which must avoid constrained prosthesis. PMID- 7784649 TI - [Upper metaphyseal lengthening of the tibia. Report of 57 cases in children and adolescents]. AB - INTRODUCTION: The authors reviewed 57 upper metaphyseal lengthenings of the tibia. They especially studied complications in order to evaluate this method. MATERIAL AND METHODS: Fifty seven tibial lengthenings in 47 children and adolescents were reviewed. All lengthenings were performed according to the callotasis technique, using Judet's lengthener in the first 15 cases, the, OF Garches Orthofix in 42 cases. All the callotasis principles were applied: delayed elongation, 1 mm per day distraction, one month neutralization after elongation period, then dynamization before removing the apparatus. Particularities were: a) metaphyseal osteotomy of the upper tibia, b) screw fixation and osteotomy of the fibula, c) classical dynamization according to De Bastiani and Aldegheri in 29 cases, dynamization by a silastic collar (OF-Dyna-Ring) in 28 cases. METHODS: Severity of complications was classified according to Caton: none, benign, serious (needed reoperation or reanesthesia) and severe (sequel). Complications and rate of lengthenings without complication or with benign complications were studied relative to etiology, age, amount of lengthening and the stage of program in which they occurred. A table summarizes data of all the lengthenings. RESULTS: Lengthening was 52.3 mm in average. Healing time (number of days to lengthen and to fuse the bone divided by the number of lengthened centimeter) was 40 in average (range: 20-105): it was 45.6 days per cm when using classical dynamization and only 34.3 with silastic collar dynamization (p = 0.002). Total of complications was 59 out of 57 lengthenings. 21 complications were benign, 37 serious and 1 severe (partial motor palsy of the foot). Thirty two (56 per cent) lengthenings were performed without unforeseen procedure or anesthesia. There were 4 intra-operative complications: 1 vascular lesion, 1 incomplete osteotomy and 2 malpositioned half screws. Complications of elongation period were the most numerous, 4 transient palsies, 6 knee contractures (2 led to a supracondylar fracture), 6 equinism (4 needed an Achilles tendon lengthening), 12 valgus deviations in which 9 were realigned using OF-Garches fixator without reoperation, 1 serious depression occurred in a bilateral lengthening. Consolidation was achieved without complication in 52 cases. Complications were: 1 refracture (fourth lengthening of the same tibia), 1 delayed union, 1 non union, 2 late deviations. DISCUSSION: Rate of nervous and joint complications is close to that of other series. However, a high osteotomy decreases the consequences on the foot without increasing knee contracture in flexion. The ability to realign during the elongation period appears to be a prevention of valgus deformity compared to Wagner's technique. The authors's distractor is better tolerated than Ilizarov's. Problems with consolidation are rare, less than 9 per cent of the cases. CONCLUSION: A modular distractor improves the results of tibial lengthening; realignment is possible before, during or after the elongation. OF-Orthofix is easy to apply and well-tolerated by the patient, especially in bilateral lengthenings. Performing a high osteotomy, the callus is thick and the consolidation is quickly achieved and safe. A well-thought dynamization using Orthofix Dyna-Ring decreases the treatment time which is 35 days per centimeter in average. PMID- 7784650 TI - [Neuro-aggressive dorsal vertebral hemangioma and vertebrectomy. Apropos of 2 cases. Review of the literature]. AB - PURPOSE OF STUDY: Vertebral hemangioma is a benign and relatively frequent lesion. It is rarely associated with medullary compression. Two cases of vertebral hemangioma with progressive neurologic deficit are presented. METHODS AND RESULTS: Successful treatment was accomplished using pre-operative embolization and vertebrectomy. The tumor was resected by an antero-lateral transthoracic and posterior approach. DISCUSSION: The technique of operative management and complications are discussed. Based on these two patients and a review of the literature, the authors recommend that management of patients with progressive neurological deficit should include pre-operative angiography and embolization, decompressive surgery with the approach determined by the degree of vertebral involvement and site of spinal compression. PMID- 7784651 TI - [Necrotizing fasciitis of the foot. An unknown surgical emergency. Apropos of a case]. AB - INTRODUCTION: The purpose of this study was to review the literature concerning Necrotizing Fasciitis (N.F.) and to discuss a typical case where late diagnosis led to severe consequences. MATERIAL AND METHODS: A young male patient with no pertinent medical history, progressively developed a large swelling of his foot and severe pain 3-4 days following a simple contusion. The absence of an entry site lead to local incision without microbiological study. The patient developed blistering on the leg, then septic shock necessitating amputation. DISCUSSION: N.F. is an infectious necrosis of the sub-cutaneous tissue appearing frequently in surgical or post traumatic contexts. Streptococcal origin is classical but multibacterial anaerobic infection is more and more frequently observed. An entry site is not always found while the affected site becomes red, hot and painful. Evolution is extremely rapid with the appearance of blisters and cutaneous necrotic sites and a severe alteration in the general condition of the patient. The extent of sub-cutaneous necrosis is larger than the affected area of skin. N.F. is a surgical emergency. Treatment consists of complete debridement, sometimes very extensive and mutilating. High dose intra-venous antibiotic therapy is necessary while the benefits of hyperbaric therapy are discussed. Because of the lack of specific clinical signs, diagnosis is difficult and is often made too late. The rapidity of the evolution shows that vital and functional prognosis is better with early diagnosis and treatment even for patients without associated pathology. The rate of mortality is approximately 50 per cent. CONCLUSION: Better information of practitioners allowing a rapid clinical diagnosis could improve the prognosis which is still life-threatening in 1994. PMID- 7784652 TI - [The present and future of transplants in Spain]. PMID- 7784653 TI - [The liver transplant program of the Hospital General Universitario Gregorio Maranon: an analysis of the first 100 patients]. AB - During a 3-year period between 1990 and 1993, 100 patients received orthotopic liver transplantation at the "Gregorio Maranon" University General Hospital. The mean age of the patients was relatively high (46.9 +/- 10 years), with an important number of cirrhotic patients (91%). The rate of primary liver failure was relatively low (4.5% of transplantations) although 12 cases with more than 55 years were included in the present series. Eleven retransplantations were performed, 8 for early failure of the graft and 3 for chronic failure. Postoperative complications of the graft were vascular in 9 cases, biliary in 17 cases, and acute rejection (cellular) in 70 patients, although only 50 of these patients required treatment with steroid boluses. Infections were diagnosed in 60 cases with 80% of major infections, 6 of them caused by Aspergillus fumigatus that were lethal in all the cases. Postoperative survival was 82%, 72%, 69% and 69% at 1 month, 6 months, 1 year and 2 years respectively. PMID- 7784654 TI - [A decrease in the basal levels of serum pepsinogen I after H. pylori eradication]. AB - Hyperpepsinogenaemia has long been considered an important factor in the pathophysiology of duodenal ulcer. Moreover, H. pylori infection has been reported in virtually all duodenal ulcers. OBJECTIVE. To demonstrate the influence of H. pylori eradication on basal pepsinogen I levels in patients with duodenal ulcer. METHODS. 86 patients with endoscopically proven duodenal ulcer were prospectively studied. Different therapeutic regimens were used: Amoxycillin/clavulanate plus omeprazole or ranitidine, triple therapy, omeprazole and ranitidine. At diagnostic endoscopy and after therapy, three biopsy samples were taken from different levels and analyzed by microbiological and histological methods; also, basal pepsinogen I levels were measured. RESULTS. H pylori eradication was associated with a significant histological improvement (p < 0.001), both in gastric antrum and corpus. In patients where H. pylori was eradicated pepsinogen I levels decreased from 107.6 +/- 31 ng/ml to 79.7 +/- 32 ng/ml after therapy (p < 0.001); however, when eradication was not achieved differences were not significant. CONCLUSION. H pylori eradication in patients with duodenal ulcer was associated with a significant decrease in basal pepsinogen I levels. The verification of such a decrease could represent a useful non-invasive method to monitor the efficiency of therapy, both in H. pylori eradication and in the resolution of the associated gastritis. This procedure is also associated with early results and a low cost. PMID- 7784655 TI - [H. pylori infection at the duodenal bulb in different endoscopic diagnoses]. AB - Biopsy samples obtained by endoscopy to diagnose infection by H. pylori usually come from the antral region. Nevertheless, there are few reports documenting the prevalence of infection at duodenal level. OBJECTIVE. To investigate the prevalence of H. pylori infection in duodenal bulb in different endoscopic diagnosis. METHODS. 331 patients with the following endoscopic diagnosis were studied: normal appearance (n = 55), gastritis (87), gastric ulcer (49), duodenal ulcer (120), and duodenitis (20). At endoscopy, different samples from duodenal bulb were obtained (apart from gastric fundus, body and antrum), which were processed for microbiology (Gram stain and culture) and histology (hematoxilin eosin). RESULTS. Patients with duodenal ulcer or duodenitis had the highest H. pylori infection rate at duodenal bulb (47.7% and 65%, respectively). Differences were significant when compared with normal appearance (14.5%; p < 0.001) and gastritis (25%; p < 0.05). In all patients with H. pylori at duodenal bulb this organism was also detected at antral region. CONCLUSIONS. 1) The highest prevalence rates for H. pylori infection in duodenal bulb were found in patients with duodenal ulcer or duodenitis. 2) Diagnosis of H. pylori infection should not be based on the duodenal bulb samples alone, as this sample yields high false negative results. PMID- 7784657 TI - [The SAPHO syndrome or psoriatic arthritis: a complicated differential diagnosis. Apropos 3 cases]. AB - SAPHO syndrome is characterized by osteoarticular involvement of ventral chest wall in the form of sternocostoclavicular osteoarthritis and hyperostosis and skin changes such as palmoplantar pustulosis and acne. Occasionally, psoriatic lesions and sacroiliitis are observed. However, despite the higher frequency of psoriasis in this syndrome, its inclusion in psoriatic arthropathy spectrum is not clearly established. The authors report three cases of SAPHO syndrome in psoriatic patients commenting on the difficulty in differentiating this entity from psoriatic arthritis as well as its relationship with seronegative spondyloarthropathies. This disease has been described mainly in Japan and only a few cases of this disease have been reported in the European or American literature. PMID- 7784656 TI - [Guidelines for the dietetic treatment of patients with anorexia nervosa based on an assessment of their nutritional status]. AB - The evaluation of the nutritional status of patients with anorexia nervosa is of great utility when establishing guidelines for specific and appropriate dietary programs to face nutritional deficiencies and thus favoring their recovery. The nutritional status of patients was evaluated by means of anthropometric, biochemical, and dietetic parameters in a group of 78 anorexics who followed a psychiatric and nutritional therapy, 57 in an ambulatory basis and 21 as in patients. Anthropometric parameters (weight and body mass index) showed a severe depletion of the nutritional status, particularly in in-patients. Only 25% of patients had a body mass index higher than 18 and 5% had values within normal ranges. While biochemical indexes (hemoglobin, hematocrit, red blood cells, mean corpuscular volume, total proteins and vitamins: thiamine, riboflavin, B6, ascorbic acid, alpha-tocopherol, retinol and beta-carotene) were within normal ranges in most cases, there were variable percentages of patients with marginal values and clearly deficient for group B vitamins: thiamine (79 +/- 11 U/l; P25 = 70 U/l), riboflavin (884 +/- 160 U/l; P5 = 640 U/l) and B6 (309 +/- 131 U/l; P25 = 227 U/l). The study of the diet showed a marked lack of energy supply (only 25% of patients had their needs satisfied (P75 = 101%) and minerals (iron, magnesium, and zinc). Intake of proteins and vitamins was, in general, satisfactory. Critical points to be considered in refeeding are energy and mineral deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784658 TI - [Cervical spondylosis: a review of up-dated concepts]. PMID- 7784659 TI - [The physiopathology of duodenal ulcer: an attempt at a link between "classical" knowledge and Helicobacter pylori infection]. PMID- 7784660 TI - [Practical toxicologic mycology for physicians. Independent synonyms]. PMID- 7784661 TI - [Painful neuropathy]. PMID- 7784662 TI - [A young woman with asthenia and electrocardiographic changes]. PMID- 7784663 TI - [Syncope and a heart murmur in a 37-year-old woman]. PMID- 7784664 TI - [A 51-year-old woman with hypothyroidism, hypogonadism and an acute picture of abdominal pain, diarrhea, vomiting, fever and hypotension]. PMID- 7784665 TI - [Cardiorespiratory arrest as the first manifestation of hypothyroidism]. PMID- 7784666 TI - [Bacteremic pneumonia due to Moraxella catarrhalis in an immunosuppressed patient]. PMID- 7784667 TI - [Laryngeal tuberculosis. A report of 3 cases]. PMID- 7784669 TI - [Epidemiological research on handicaps in children]. PMID- 7784668 TI - [Monoclonal gammopathy and anti-HCV: a mixed cryoglobulinemia?]. PMID- 7784670 TI - [Comparative analysis of the costs of cytogenetic techniques and molecular biology techniques in the diagnosis of fragile X disease]. AB - Mental retardation is sometimes due to chromosomal abnormalities. Most frequent illnesses are Down syndrome and Fragile X syndrome. Using a cost analysis, we try to see what diagnosis method is the most relevant to find chromosomic causes for mental retardation in an institutionalized male population. Two techniques are compared: cytogenetic technique and molecular biology technique. Four diagnostic strategies are identified. They all have the same effectiveness, but, costs vary. Results depend on prevalence rates in the epidemiologic literature on Fragile X syndrome and other chromosomic abnormalities. The least-cost diagnostic strategy is molecular biology then constitutional karyotype in case of a negative result. This strategy costs about 600 FF1991 less compared with Fragile X karyotype and about 120 FF1991 less than when molecular biology is done in second, for fixed prevalence rates (i.e. Fragile X prevalence rate between 4.5 and 10% and other abnormalities between 2.2 and 25%). Fragile X karyotype strategy has the highest cost whatever the prevalence rates. Those results are discussed when introducing female population and delay to test results for prenatal diagnosis. PMID- 7784671 TI - [Risk factors in prematurity and intrauterine growth retardation in Burkina Faso]. AB - A case-control study to investigate determinants of preterm delivery and intrauterine growth retardation (IUGR) in Bobo-Dioulasso, Burkina Faso, was conducted between December 1991 and November 1992. A total of 581 cases were recruited, 281 preterm infants with birthweight < 2500 g and 300 term infants with birthweight < 2500 g. 578 infants born at term with birthweights of 2500 g or more were recruited as controls. Logistic regression analyses identified three factors linked independently to both preterm delivery and IUGR: maternal illness during the pregnancy, nulliparity and failure to attend three antenatal consultations. In addition, primiparity and a maternal weight < 50 kg were associated with an increased risk of preterm delivery. Other factors associated with increased risk of IUGR were maternal height less than or equal to 155 cm, mid-upper arm circumference < 24 cm, and female sex of the infant. Improvements in the pre-pregnancy weight of women and in antenatal care focused on nulli- and primiparous women might in this population, reduce substantially the incidence of preterm delivery and IUGR. PMID- 7784672 TI - Prevalence of non-insulin dependent diabetes as perceived by general practitioners in France. AB - A representative, random sample of French general practitioners, reported the number of diabetic patients they treated in their practices. The resulting NIDDM prevalence rate for France was 1.71% (SE +/- 0.03), compatible with the rates found in other studies. Prevalence rates for NIDDM were also calculated by region and a multivariate covariance model was used to correlate the prevalence with known risk factors. The three significant factors were: the quantity of wine consumed, the female/male sex ratio of people over 45 years of age, both positively correlated, and the consumption of animal fats, which was negatively correlated with NIDDM prevalence. PMID- 7784674 TI - [Comparison of 3 quality of life instruments in the longitudinal study of rheumatoid arthritis]. AB - Quality of life measures take into account the patient's perception of health. Many generic or specific instruments are available. The psychometric properties of such measures should allow for adequately testing the hypothesis of an investigation. We studied the properties of three quality of life measures: the Health Assessment Questionnaire (HAQ) specific for rheumatic diseases, the Nottingham Health Profile (NHP)--a generic measure--and the General Health Questionnaire (GHQ) which measures psychological dimensions. They were applied in a one year cohort study of 111 French rheumatoid arthritis patients set up for determining prognosis factors of quality of life. Criterion validity was established on high correlation between Ritchie index and physical dimensions (r = 0.29 to 0.58, p < 0.01). Internal consistency was good with Cronbach's alpha coefficients over 0.8 for all dimensions. Reproducibility was studied for physical dimensions with Intra-class Correlation Coefficient (ICC) for patients clinically unchanged. It was excellent for the HAQ (ICC = 0.89), good for the NHP (ICC = 0.57 to 0.73) but weak for the GHQ (ICC = 0.13 for somatic dimension). After one year follow-up, a significant change in quality of life could only be evidenced by the HAQ (Standardized Response Mean = 0.4, p < 0.05) in patients with clinical significant change. So among the three instruments, the HAQ should be preferred for longitudinal studies, possibly supplemented with a generic instrument that investigates more dimensions of quality of life. PMID- 7784673 TI - Misuse of pressurized metered dose inhalers by asthmatic patients treated in French private practice. AB - Although metered dose inhalers (MDIs) are widely used to treat asthma, clinical studies suggest that misuse is frequent. We studied the frequency of, and factors related to, misuse of MDIs in asthmatic patients of French private practice. 264 chest specialists or general practitioners completed questionnaires including characteristics of patients and asthma, technique in using inhalers and previous instruction, for three consecutive asthmatics aged > 6 years and currently using MDIs: 668 adults (mean age 47.8 years +/- 18.5, 51.8% males) and 100 children (mean age 11.5 years +/- 2.1, 72.0% males) were included. Adequate technique (deep inspiration synchronized with inhaler activation, followed by holding breath for 5 seconds) was used by 33.2% of adults and 26.0% of children; optimal technique (same, plus shaking the inhaler before use and activating it only once) was used by 22.1% of adults and 20.0% of children. The main factor related to misuse of MDIs was absence of previous instruction. However only 26.5% of instructed adults and 22.1% of instructed children used the optimal technique. Misuse of MDIs is a public health problem and instruction is unlikely to solve it. The use of different types of devices, like dry powder breath-actuated inhalers should be encouraged. PMID- 7784675 TI - [Relationship between perceived health status and career choice in a sample of wage-earners]. AB - Many factors were related with subjective health status (SHS), but few studies have focused on identifying some intrinsic personal factors like the choice of job and perceived working situations. The present paper examines the relationships among such factors in a large French sample. Data were collected from 21,378 subjects who were randomly selected from the lists of male and female wage earners who were followed up by 380 occupational physicians and who were born in 1938, 1943, 1948 or 1953. SHS was evaluated using the French version of the Nottingham Health Profile (NHP). Socio-demographic and job characteristics were assessed by means of closed questions during the annual medical examination. Results showed that low subjective health status was related to sex, age and perceived working situation: for each of the six areas of the NHP (pain, physical mobility, energy, sleep, social isolation, emotional reactions) there was a lower SHS for women and a decrease with age for both sexes. The poorer the perceived working situations the worse was the SHS. Using general linear models it appeared that independently of these factors and the socio-economical category dichotomized in upper classes versus lower classes, those who had claimed to have not chosen their job had a lower SHS, whatever the area of SHS. Awaiting the second survey in 1995, it is difficult to explain these results from this cross sectional analysis: is the choice of job a possible risk factor or an artefact due to some unmeasured confounding factors like motivation or job satisfaction. PMID- 7784676 TI - [Levels of low birth-weight in Europe: registration problems and effects of medical interventions]. AB - The rate of low birthweight births, percentage of live births weighing less than 2500 grams is one of the perinatal health indicators recommended by the World Health Organisation. A review of the literature has revealed numerous problems related to this indicator. Some countries, including France and the Netherlands do not collect birthweight data. Elsewhere, there are more than 10% "unknown birthweight". The poorest registration is for birthweights below 1000 grams. Exclusion of babies who were registered as stillborn, when in fact they died shortly after birth can cause underregistration of low birthweights. Conversely, inclusion of true stillbirths will bring on an overestimation of low birthweight rate. Some countries have too few births to deliver accurate rates. Rates of medical interventions, such as infertility treatment and elective induction should be taken into account when analyzing differences between countries. Improvement in quality of registration and caution in the use of this indicator are warranted. PMID- 7784677 TI - Daily smoking among adolescents in the European Community. PMID- 7784679 TI - [Evaluation of a self-assessment questionnaire with optical reader in a cohort study]. PMID- 7784678 TI - [Surveillance of HIV infection in children in Europe]. PMID- 7784680 TI - [HIV-1 infection: how are long-term asymptomatic subjects characterized?]. PMID- 7784681 TI - [Breast cancer between 2 screenings: is a 3-year interval too long?]. PMID- 7784682 TI - [Obstetric analgesia. Still controversial?]. PMID- 7784683 TI - [Comparative study of single-dose intradural anesthesia and continuous intradural anesthesia with or without fentanyl]. AB - OBJECTIVE: To compare the hemodynamic effects, level of anesthetic blockade and advantages of single-dose versus continuous intrathecal anesthesia with hyperbaric bupivacaine with and without fentanyl. PATIENTS AND METHOD: Prospective study in 45 patients under 65 who were scheduled for elective surgery of the lower abdomen, randomly divided into 3 groups. Group 1 and 2 received continuous intrathecal anesthesia with 10 mg hyperbaric bupivacaine; group 2 also received 25 mcg fentanyl. Patients in group 3 were given a single intrathecal dose of 15 mg hyperbaric bupivacaine. Mean arterial pressure and heart rate were recorded at baseline and 10, 20 and 30 minutes after the start of anesthesia. The level of block achieved was recorded after 10, 30 and 60 minutes. Hemodynamic changes, differences in blockade and side effects were analyzed. RESULTS: Hemodynamic changes were greater in group 2 (fentanyl) than in groups 1 and 3 (p < 0.05), with group 3 showing the greatest degree of hemodynamic stability. Level of blockade was always higher in group 2, with significant differences at 30 min (p < 0.05). Seven and 5 reinjections by catheter were necessary in groups 1 and 2, respectively. Two patients in group 3 required general anesthesia when blockade was inadequate. Apart from pruritus in group 2 (40%), no side effects due to anesthesia were observed. CONCLUSIONS: A single dose intrathecal anesthesia, produces less hemodynamic changes than a continuous intrathecal block. Nevertheless, continuous intrathecal block, allows the maintenance of the block as long as required. The association of fentanyl enhances the hemodynamic changes with no other beneficial effects. PMID- 7784685 TI - [Analgesia of postoperative pain in ambulatory surgery]. AB - Although the role of outpatient surgery has become increasingly important in the campaign to reduce waiting lists and health care costs, careful control and treatment of postoperative pain too often receives slight attention. Pain control after surgery must produce high quality analgesia without lengthening the hospital stay or increasing the risk of complications. The risk of side effects must be low, the safety margin wide and administration simple. Anesthesiologists must therefore take preventive measures as well as apply techniques during and after surgery that diminish the intensity of pain and the incidence of nausea or vomiting. Drugs that act in the short term and have few side effects, regional anesthesia (depending on type of operation), non-opioid analgesics and balanced analgesia seem to give good quality control of pain after outpatient surgery. PMID- 7784684 TI - [Published books on pain and its treatment in Spain. Analysis with the ISBN database]. AB - INTRODUCTION: Although analyses have been done on the publishing of scientific articles on pain in Spanish, book publications in the field have not been studied. This article fills that gap. MATERIAL AND METHODS: A bibliography of books with pain approached from a medical standpoint was compiled from ISBN CD ROM database (updated for 1993). Books going into more than one edition were considered single titles. Multi-volume collections were considered single books. We analyzed type of book, subject, ISBN classification, year, language (of publication and original), publisher and place of publication. RESULTS: Two hundred books were studied. Over 60% had been published within the previous 10 years. The year that showed the most books published was 1990 (19) followed by 1989 (16) and 1988 (16). Output has been rising steadily. One hundred ninety eight books were published in Spanish and 2 in Catalan. The original language was Spanish in 114 cases, English in 51 cases, French in 21 and German in 7. By ISBN classification, most (146) covered pathology, disease and medical/therapeutic clinical practice. By topic, 51 books were general, 41 treated lumbalgia, sciatica or back pain and 35 covered headaches in general or migraine. Most of the books were issued by trade publishers. The cities most often involved were Barcelona and Madrid. CONCLUSIONS: An increased number of books about pain are being published in Spain, coinciding with a rise in the publication of scientific articles on the subject. PMID- 7784686 TI - [Obstetric anesthesia-analgesia in Spain. A review of its historic evolution during the second half of the past century]. AB - To examine the historical development of obstetric anesthesia in Spain during the second half of the nineteenth century. Research was based on in-depth analysis of accounts of anesthesia during the period covered, mainly from original sources, using established methods for studying the history of medicine. We collected a great deal of documentary evidence, much of it unpublished and of clear historical value for tracing the history of obstetric anesthesia in Spain and identifying the main factors that have influenced it. We emphasize that controversy limited to a large extent the use of anesthesia in obstetrics. The controversy seems to have been fed by physicians' uneasiness with anesthesia as well as by certain prejudices of a religious or moral nature that are deeply rooted in Spanish society. PMID- 7784687 TI - [Anesthetic management of labor in a pregnant woman with myocardial infarction]. AB - Given the rarity of acute myocardial infarction (AMI) in parturients, we report the case of a 29-years-old woman who suffered 2 AMIs related to her 2 pregnancies. In our patient, the anesthetic technique chosen for the second birth, which was vaginal, was epidural analgesia with invasive hemodynamic monitoring. No complications occurred during the birth or the perinatal period. PMID- 7784688 TI - [Placenta praevia accreta and obstetric hysterectomy]. AB - We present the case of a 38-years-old tertipara at full term with a diagnosis by ultrasound of placenta previa who underwent elective cesarean under spinal anesthesia. After a difficult birth, anomalous adhesion of the placenta prevented its removal and caused massive hemorrhage of the placental bed and hypovolemic shock. Blood volume was restored and emergency hysterectomy under general anesthesia was effected, as bleeding and hemodynamic state were brought under control. Abnormal heart rhythm appearing after the operation responded to treatment; postoperative recovery was unremarkable. Placenta accreta is a rare complication of placenta previa. Given that massive obstetric hemorrhage is associated with significant mortality and morbidity, both maternal and fetal, the anesthesiologist must be aware of potential problems that might arise in cases of placental accreta so that readiness can keep risk to a minimum. PMID- 7784689 TI - [HELLP syndrome and its complications during preeclampsia-eclampsia]. AB - HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) is a rare complication that can appear during and/or after pregnancy in patients with preeclampsia or eclampsia. As the syndrome can have serious complications, early diagnosis is important for management. We describe a patient with HELLP syndrome who developed one of its unusual but severe complications: ruptured liver capsule. PMID- 7784690 TI - [Anuria in the third trimester of pregnancy in a patient with renal transplant]. AB - We present a pregnant patient with a transplanted kidney experiencing chronic rejection, with chronic kidney failure and arterial hypertension. During the third trimester the patient's kidney function deteriorated somewhat and hypertension worsened. In the thirty-second week of pregnancy uterine activity increased, fetal movement decreased and oliguria progressed rapidly to anuria, leading to an emergency cesarean section. Surgery was performed under epidural anesthesia; after removal of the fetus diuresis immediately began and was maintained. Both mother and infant recovered, but after three months the patient entered a hemodialysis program due to terminal kidney failure. The risk of acute kidney failure is greater in the parturient who has been the recipient of a transplanted kidney because of the functional overload that pregnancy involves, the possible exacerbation of acute or chronic rejection, and the higher incidence of pyelonephritis and preeclampsia. The extraperitoneal location of the transplanted organ in the iliac fossa may cause obstructive anuria. Our patient's recovery of diuresis immediately after removal of the fetus suggests that the excretory channel coming from the kidney was compressed by the uterus. PMID- 7784691 TI - [Anesthetic management of abdominal pregnancy and postoperative complications]. PMID- 7784692 TI - [Intraoperative rupture of subclavian aneurysm caused by self intra-arterial injections in a drug addict]. PMID- 7784693 TI - [Diagnostic value of microalbuminuria and the calcium/creatinine ratio in the early detection of preeclampsia]. AB - We have evaluated the biochemical and clinical parameters for early detection of their alterations in pregnant women with late preeclampsia. Eighty nine patients between 24 and 32 gestation weeks were studied. Fifteen of them (18%) developed arterial hypertension (mean 141.5 +/- 3mmHg). The perinatal results, gestational age at delivery, birth weight and Apgar score of the newborns were not significantly different among the groups that were evaluated. The microalbuminuria was analyzed through radioimmunoanalysis and reactive strips for the immunochemical semiquantitative determination. The calciura was analyzed using the compleximetric method and the urinary creatine using the colorimetric method of Jaffe. No significative differences were found among the results of each evaluated method. The RIA showed greater sensibility, greater specificity and greater positive or negative predictive value with respect to other methods, but the differences were not wide enough to consider it the method of choice. In the group of patients (n = 15) who developed arterial hypertension, all the biochemical methods showed a normality higher than 80%. We conclude that none of these methods used alone is useful for the early prediction of the appearance of preeclampsia. PMID- 7784694 TI - [Angiolymphoid hyperplasia: clinico-pathological considerations]. AB - Two cases of angiolymphoid hyperplasia with eosinophilia or Kimura's disease are presented. A nodular and papuoid pattern of presentation was observed. The first one is the histologic expression of the vascular and cellular components which were found in the subcutaneous fat whereas the latter was in the dermis. Clinical and pathological considerations were made to differentiate both illnesses. However, due to the overlapping of certain criteria it is considered that we are dealing with the same disease at different phases. PMID- 7784695 TI - [PAS-positive T-lymphocytes in chagasic cardiomyoneuropathy. I. Immunopathologic mechanisms in Chagas]. PMID- 7784696 TI - [An experience with teaching training at the School of Medical Sciences of the National University of Cordoba]. PMID- 7784697 TI - [Quantitative study of encephalic components in 3 tinamid species, with an ecoethological approach (birds: Tinamidae)]. AB - The encephalon of three tinamids: Eudromia elegans, Nothura maculosa, and Rhynchotus rufescens are quantitatively analyzed. Both relative volumes and cerebral indexes are calculated for eleven encephalic components. Results are discussed from an eco-etiological approach. The relative size of encephalic components in Eudromia, Rhynchotus, and Nothura indicate a close relationship among brain components and some behavioral patterns and the environment. Marked differences in the cerebral organization of these tinamid genera are not evident. A greater development of the wulst and low values of olfactory bulbs suggest that Eudromia and Rhynchotus are progressive species. Nothura is considered primitive. PMID- 7784698 TI - [Treatment of non tuberculous mycobacteriosis with quinolones]. AB - Two cases of Non-tuberculous Mycobacterium from the MAI group and another by Mycobacterium Fortuitum are presented. None of them with extrapulmonary manifestations. They were treated with a scheme of four drugs among which the Quinolone was included. The patients were adults with pulmonary processes clinically and radiologically similar to pulmonary Tuberculosis (TBC); non tuberculous mycobacteria were isolated from the sputum. It has been shown "in vitro" that the nontuberculous mycobacteria are sensitive to the Fluoroquinolones. Thus, Ciprofloxacine or Ofloxacine were used, taking into consideration the initial polirresistence to the habitual tuberculostatics. Consequently, these patients were treated with schemes which included these new Quinolones, getting good clinical responsiveness and negativization of the sputum in all the cases. PMID- 7784699 TI - Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs. AB - The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n = 5), an 84% Hx group (n = 5) and an 84% Hx+PSS group (n = 5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immunohistochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs. PMID- 7784700 TI - Semi-quantitative analysis of cytokine gene expression in blood and cerebrospinal fluid cells by reverse transcriptase polymerase chain reaction. AB - An easy, reproducible and semi-quantitative, non-radioactive method for the analysis of mRNA expression for various cytokines, (i.e., Interleukin (IL)-1 beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, lymphotoxin (LT), transforming growth factor (TGF)-beta, interferon (IFN)-gamma and endothelin-1 (ET-1)) in cells from cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) has been established. By means of polymerase chain reaction primers that cover a splice junction, amplification of contaminating DNA was omitted. Densitometric scanning of ethidium bromide-stained agarose gels proved to be very sensitive for semiquantitative analysis of PCR products. Serial tenfold dilutions of cDNA revealed a log-linear regression from 10(6) to 10(2) cells under optimal cycle conditions. The intra- and inter-assay variability of the method was below 10%. With this assay, the cytokine expression pattern of as few as 10(4) mononuclear cells from blood or CSF was determined. This method made it possible to detect differences in the cytokine gene expression pattern of mononuclear cells from patients with different neurological diseases. CSF cells from 43 patients with various neurological diseases were analyzed. TNF-alpha, LT, and IL 1 mRNA were prominent in the CSF cells of most patients with bacterial meningitis. TNF-alpha, LT, IFN-gamma and IL-6 mRNAs were detected in patients with active multiple sclerosis, whereas TNF-alpha, IL-6, and endothelin-1 mRNA expression was found frequently in patients with HIV encephalitis. Pro inflammatory cytokines were rarely detected in CSF cells from patients with non inflammatory diseases of the central nervous system. In blood mononuclear cells from patients with multiple sclerosis, TNF-alpha mRNA expression was associated with disease activity. The sensitivity, specificity, velocity and reliability of this assay considerably facilitates the analysis of cytokine production in mononuclear cells even in conditions where only a limited number of cells is available for analysis. PMID- 7784701 TI - Experimental evaluation of peritoneum and pericardium as dural substitutes. AB - Although many substances have been tested in the search for an ideal dural substitute, an entirely satisfactory material has still not been found. The authors report an experimental study involving the closure of dural defects in rabbits with biomaterials developed from pig peritoneum and pericardium. Macroscopic and histologic examination, performed over a period between 15 and 45 days after implantation showed slight or no adhesion between the graft material and the cortex. No infection, CSF leakage, fistula or toxicity was noticed. The results demonstrated that these biomaterials could be used as satisfactory dural substitutes. PMID- 7784702 TI - Differing kinase activity of the c-yes and c-src gene proteins in TPA-induced megakaryocytic differentiation of T-33 and K562 cell lines. AB - We examined the protein kinase (PK) activity of the c-yes and c-src gene proteins (c-YES, c-SRC) at an early phase of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced megakaryocytic differentiation of T-33 and K562 cells with use of immunoprecipitation and in vitro kinase assay. We found that c-SRC PK activity of TPA-treated T-33 and K562 cell lines had been enhanced compared with the untreated ones, but in contrast, no enhancement of c-YES PK activity by the TPA treatment was observed in these cell lines. We also examined PK activity in TPA induced monocytic differentiation of U937 monoblastic cells that exhibited no megakaryocytic markers and found that both the c-YES and c-SRC PK activity was enhanced by the TPA treatment. Our data suggest that c-YES and c-SRC play different and unique roles in TPA-induced megakaryocytic differentiation in T-33 and K562 cells. PMID- 7784703 TI - Delayed gastric emptying in conscious male rats following chronic estrogen and progesterone treatment. AB - Several clinical observations and animal experiments have led to speculation concerning the possible effects of pregnancy and pregnancy-associated sex steroids on gastrointestinal function. It was reported that estrogen increases intestinal contractile activity, while progesterone or the combination of estrogen and progesterone decreases it. In order to measure gastric emptying, a methylcellulose test meal was given orally into the stomach of conscious rats. In progesterone-treated rats, at the dose of 0.2 mg/kg, gastric emptying was not significantly different from that of the control, but it was found to be significantly delayed at the dose of 10 mg/kg (P < 0.05). Estrogen treatment at doses of 20 micrograms/kg and 600 micrograms/kg significantly delayed gastric emptying, when compared with controls (P < 0.001). Combined therapy of estrogen and progesterone induced a significant delay in gastric emptying rate compared with the control group (P < 0.001). In the animals with pseudopregnancy treatment (100 micrograms/kg estrogen+ 15 mg/kg progesterone; 7-12 days) the gastric emptying rate was significantly different from that of the control (P < 0.05). We conclude that both estrogen and progesterone exert inhibitory effects on gastric emptying, and this may account for the disturbances in gastrointestinal function that pregnant women frequently experience. PMID- 7784704 TI - Influence of chronic liver damage on regeneration of the organ in rats. AB - To investigate the influence of chronic hepatic damage on liver regeneration, a 70% hepatectomy was carried out in male BDE rats in which chronic hepatic damage had been induced by i.m. injection of 0.1 ml CCl4/100 g b. w. twice a week for 4 weeks. After resection, we examined adenine nucleotide concentration in the remaining liver tissues, also body weight and wet and dry weight of the liver. The total adenine nucleotide concentration fell 6 h after resection from 2.89 +/- 0.22 mumol/g to 2.03 +/- 0.15 mumol/g and then recovered on the 3rd postoperative day. However, control animals showed lowest values 3 h after resection, and had already begun to recover at 6 h. Energy charges fell 3 h after liver both groups to the lowest values, but recovery was slower in the animals with chronic liver damage. These observations suggest that in animals with hepatic damage regeneration is delayed in the initial post-resection period. However, 5 days after resection the wet and dry weights of the liver were completely normalized and there was no difference between the two groups, i.e., 5 days after 70% liver resection we could not find any delayed regeneration tendency in animals with chronic liver damage. PMID- 7784705 TI - Pulmonary damage due to paraquat poisoning through skin absorption. AB - A case of recovery from acute respiratory insufficiency due to paraquat is described. A 57-year-old farmer developed breathlessness, high fever and interstitial infiltrates in the upper and middle lung fields few days after percutaneous paraquat poisoning with rapid evolution to pulmonary fibrosis. Anti inflammatory drugs and antioxidants, were administered to the patient, though with a delay, with some improvement; the patient survived despite residual lung fibrosis. Paraquat lung, as confirmed by this paper, is not invariably fatal. PMID- 7784706 TI - Fatal intrathoracic hemorrhage in a patient with von Recklinghausen's disease. AB - Neurofibromatosis can involve the mediastinum. A 44-year-old woman with a dumbbell-shaped mediastinal mass developed a large pleural effusion, respiratory failure and fatal hemoptysis. Autopsy revealed systemic neurofibromatosis involving the mediastinum and pleura. Mediastinal and pleural hemorrhage probably occurred as a result of an eroded thoracic artery. Massive hemorrhage in mediastinal neurofibromatosis occurs uncommonly but with potentially fatal results. PMID- 7784707 TI - Pneumonia caused by Listeria monocytogenes. AB - Pneumonia due to Listeria monocytogenes is extremely uncommon. We report the case of an 87-year-old woman with no underlying immunosuppressive disease who presented with listerial pneumonia. Cutaneous anergy and a decrease in total lymphocyte count in this elderly woman could predispose her to listerial infection. PMID- 7784708 TI - Lymphoepithelial cysts in the mediastinum with an opening to the trachea. AB - A case of lymphoepithelial cysts (LECs) in the mediastinum, manifested radiographically by paratracheal air collection, is reported. Percutaneous injection of radiopaque material and indocyanine green into a cyst showed an opening to the trachea. During surgical resection, three well-circumscribed cysts were isolated. Pathologically the cysts were lined by a ciliated columnar epithelium and surrounded by lymphoid tissue with germinal centers. Judging from the level of the duct opening onto the airway, these LECs might have derived from a remnant of the fourth branchial pouch. To the authors' knowledge, this is the first case described. PMID- 7784709 TI - Necrotizing bronchitis, angiitis, and amyloidosis associated with chronic Q fever. AB - The authors report the clinical, radiological and histological findings in a 63 year-old male patient who developed severe necrotizing bronchitis, necrotizing angiitis, and secondary amyloidosis of the right upper love and intermediate bronchus. The patient expired due to respiratory insufficiency. At the age of 27 years, the patient had had radiotherapy of the mediastinum because of suspected Hodgkin's disease. Acute pneumonia suggestive of Q-fever infection was diagnosed at the age of 48. Progressive restrictive lung disease developed during the last decade. Serological evaluation revealed IgM and IgA high titers against Coxiella burnetii. IgA, complement and amyloid deposits were detected in the walls of small arteries. Bronchial lavage and pleural effusions displayed numerous activated T lymphocytes. Analysis of endogenous lectins revealed alterations of the pulmonary defense system. The clinical history, histological and immunological findings suggest that chronic Q fever may induce remarkable changes in the immune system, comparable to autoimmune-reactive diseases. PMID- 7784710 TI - Pleural cholesterol in differentiating transudates and exudates. A prospective study of 232 cases. AB - Two hundred and four patients with pleural effusion were studied to investigate the utility of Light's criteria and pleural fluid cholesterol level (pCHOL) in the identification of exudative pleural effusion (EPE) and transudative pleural effusion (TPE). There were 48 TPE, 56 tumor, 47 tuberculous, 30 metapneumonic and 23 miscellaneous patients. A value > or = 54 mg/dl for pCHOL and > or = 0.32 for the pleura/serum cholesterol ratio (p/sCHOL) showed sensitivity (S) and specificity (Sp) of 95.5% and 91.6% for pCHOL, and 97.4% and 91.6% for p/sCHOL, respectively. Combined pCHOL and/or p/sCHOL showed a S of 98.7% and Sp of 89.5%. Light's criteria achieved a S of 100% and Sp of 64.5%. Combined pCHOL and p/sCHOL revealed a similar accuracy to Light's criteria in EPE diagnosis but was found to be more exact in TPE diagnosis. PMID- 7784712 TI - Hypercapnic ventilation response in patients with lung disease: improved accuracy by correcting for ventilation ability. AB - The hypercapnic ventilation response (HCVR) is positively correlated with forced expired volume in 1 s (FEV1). Therefore, subjects of small stature or patients with lung disease have low values for HCVR. However, indexing the HCVR for the subject's predicted maximal voluntary ventilation (MVV) results in a corrected HCVR (CHCVR) which is not dependent on FEV1 in normal subjects [Respiration 1993;60:197-202]. We hypothesized that the CHCVR would also be useful in assessing chemosensitivity in patients with poor lung function. To obtain the predicted MVV, we used the linear regression for FEV1 vs. measured MVV obtained from 411 patients with a wide range of FEV1 values (MVV = 31.2 x FEV1 + 11.8, r = 0.90, p < 0.001). We compared HCVR and CHCVR to the occlusion pressure response to hypercapnia (OPRH) in 34 patients with chronic obstructive pulmonary disease (COPD) and in 19 patients with low FEV1 due to small stature. All patients had been referred for assessment of possible sleep apnea. The results for the two groups of patients were similar. For the COPD patients, the HCVR had high values for sensitivity (86%) and negative predictive value (94%), but specificity, positive predictive value and accuracy were low (59, 35 and 65%, respectively). In contrast, CHCVR had high values for all the foregoing (86, 96, 100, 100 and 97%, respectively). Our results suggest that the CHCVR is useful in assessing chemosensitivity in patients who are ventilation-limited. PMID- 7784711 TI - Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic pulmonary fibrosis and its clinical significance. AB - Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid associated glycoprotein in pulmonary surfactant, which is specific to the lung. In this study, the SP-A concentrations in sera of patients with various lung diseases were determined using an enzyme-linked immunosorbent assay. Patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis (PAP) exhibited prominently high concentrations of serum SP-A compared to those of other lung diseases and healthy volunteers, although there were significant increases in serum SP-A concentrations in patients with pulmonary tuberculosis, chronic pulmonary emphysema, diffuse panbronchiolitis and bacterial pneumonia compared to those of healthy volunteers. Successive measurement in 2 patients with IPF showed that serum SP-A levels reflect the disease activity of IPF. In patients with IPF, serum SP-A concentrations were significantly correlated with those of serum lactate dehydrogenase, whereas there were no significant correlations of serum SP-A concentrations with erythrocyte sedimentation rate, arterial oxygen saturation, vital capacity and carbon monoxide diffusing capacity. Determination of serum SP-A will contribute to diagnosing IPF and PAP, and may reflect the disease activity of IPF. PMID- 7784714 TI - Pulmonary infections in bone marrow transplantation: the Hong Kong experience. AB - The pattern of pulmonary infections in 59 consecutive bone marrow transplantations in Hong Kong was reviewed. Compared with published data from other marrow transplant units, we had a lower incidence of cytomegalovirus pneumonitis (1.7%) and a higher incidence of mycobacterial infections (5%). The latter is probably related to the high background prevalence of tuberculosis in the local population. Treatment with antituberculous drugs was effective. PMID- 7784713 TI - Preliminary evidence that augmentation therapy diminishes degradation of cross linked elastin in alpha-1-antitrypsin-deficient humans. AB - It is hypothesized that emphysema develops in some severely alpha 1-antitrypsin (AAT)-deficient persons because endogenous elastases are not adequately controlled by AAT, and accelerated elastin degradation occurs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung disease. Two severely deficient, PiZ patients were studied, a 63-year-old never-smoking woman with bronchiectasis and a 41-year-old smoking man with emphysema. Urinary desmosine (DES) was determined before and after augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pretreatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) micrograms/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) micrograms/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respectively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) microgram/g creatinine (p < 0.05). We conclude that monthly AAT augmentation therapy decreased DES excretion in the urine of these PiZ patients. We speculate that since there was lung disease in both patients, a decrease in degradation of lung elastin is the most likely explanation for this observation. PMID- 7784715 TI - Circulating gamma delta-T-cell-receptor-positive lymphocytes in sarcoidosis. AB - We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis. PMID- 7784716 TI - Stimulatory effect of 1 alpha,25-dihydroxyvitamin D3 on mouse alveolar macrophage tumor necrosis factor-alpha production in vitro: involvement of protein kinase C and Ca2+/calmodulin-dependent kinase. AB - 1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3, calcitriol] has been shown to modulate the immune function of peripheral monocytes and peritoneal macrophages. However, its effect on alveolar macrophage (AM) cytokine secretion has not been reported. We therefore investigated the influence of calcitriol on tumor necrosis factor (TNF-alpha) production by murine AMs and attempted to elucidate changes in the signal transduction system involved in such effects. Calcitriol significantly enhanced TNF-alpha secretion by AM stimulated with either lipopolysaccharide (LPS; 10 micrograms/ml; p < 0.005) or phorbol 12-myristate 13-acetate (PMA; 100 ng/ml; p < 0.05) at low doses (between 10(-11) and 10(-9) M). However the protein kinase C (PKC) inhibitor, H7 (10 microM), and the Ca2+/calmodulin inhibitor, W7 (25 microM), reversed such calcitriol effects. Calcitriol increased the total PKC activity of AMs. These findings indicate that calcitriol enhances both LPS- and PMA-stimulated TNF-alpha secretion through PKC- or Ca2+/calmodulin-dependent pathways. PMID- 7784717 TI - Effect of three different doses of a slow-release theophylline formulation on bronchial response to inhaled methacholine in asthmatic patients. AB - This study investigated whether or not a sustained release formulation of theophylline (SRT) at different dosages had any effect on bronchial hyperresponsiveness as measured by the methacholine challenge. On four separate occasions, 16 patients with mild asthma took either placebo or 300, 400, 500 mg of SRT twice a day. SRT had a slight bronchodilating effect that was not dose related, but produced a dose-related decrease in the bronchial response to inhaled methacholine (r = 0.39, p = 0.007). This effect was present after all three treatment periods with the active drug when mean +/- SE theophylline serum concentrations of 10.3 +/- 0.7, 12.6 +/- 0.9 and 17.1 +/- 1.1 mg/l respectively were reached. A highly significant relationship between theophylline serum concentration and the degree of protection against methacholine bronchospasm was also found (r = 0.45, p = 0.001). It is concluded that oral theophylline does reduce bronchial hyperresponsiveness in a dose dependent fashion, this effect being present at all the serum concentrations within the normal range. PMID- 7784718 TI - Hospital mortality after out-of-hospital cardiac arrest among patients found in ventricular fibrillation. AB - The aim of this study was to describe factors associated with in-hospital mortality among patients being hospitalised after out-of-hospital cardiac arrest and who were found in ventricular fibrillation. The study was set in the community of Goteborg, Sweden. The subjects consisted of all patients who were hospitalised alive after out-of-hospital cardiac arrest, being reached by our mobile coronary care unit and who were found in ventricular fibrillation, between 1981 and 1992. In all, 488 patients fulfilled the inclusion criteria of which 262 (54%) died during initial hospitalization. In a multivariate analysis including age, sex, history of cardiovascular disease, chronic medication prior to arrest and circumstances at the time of arrest, the following appeared as independent predictors of hospital mortality: (1) interval between collapse and first defibrillation (P < 0.001); (2) on chronic medication with diuretics (P < 0.01); (3) age (P < 0.01); (4) bystander initiated CPR (P < 0.05); and (5) a history of diabetes (P < 0.05). In a multivariate analysis considering various aspects of status on admission to hospital, the following were independently associated with death: (1) degree of consciousness (P < 0.001) and (2) systolic blood pressure (P < 0.05). In conclusion, among patients with out of hospital cardiac arrest found in ventricular fibrillation and being hospitalised alive, 54% died in hospital. The in-hospital mortality was related to patient characteristics before the cardiac arrest as well as to factors at the resuscitation itself. PMID- 7784719 TI - Comparison of exertion required to perform standard and active compression decompression cardiopulmonary resuscitation. AB - OBJECTIVE: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) utilizes a hand-held suction device with a pressure gauge that enables the operator to compress as well as actively decompress the chest. This new CPR method improves hemodynamic and ventilatory parameters when compared with standard CPR. ACD-CPR is easy to perform but may be more labor intensive. The purpose of this study was to quantify and compare the work required to perform ACD and standard CPR. METHODS: Cardiopulmonary testing was performed on six basic cardiac life support- and ACD-trained St. Paul, MN fire-fighter personnel during performance of 10 min each of ACD and standard CPR on a mannequin equipped with a compression gauge. The order of CPR techniques was determined randomly with > 1 h between each study. Each CPR method was performed at 80 compressions/min (timed with a metronome), to a depth of 1.5-2 inches, and with a 50% duty cycle. RESULTS: Baseline cardiopulmonary measurements were similar at rest prior to performance of both CPR methods. During standard and ACD-CPR, respectively, rate pressure product was 18.2 +/- 3.0 vs. 23.8 +/- 1.7 (x 1000, P < 0.01); mean oxygen consumption 15.98 +/- 2.29 vs. 20.07 +/- 2.10 ml/kg/min or 4.6 +/- 0.7 vs. 5.7 +/- 0.6 METS (P < 0.01); carbon dioxide production 1115.7 +/- 110 vs. 1459.1 +/- 176 ml/min; respiratory exchange ratio 0.88 +/- 0.04 vs. 0.92 +/- 0.04 (P = NS); and minute ventilation 35.5 +/- 5.1 vs. 45.6 +/- 9.2 l/min (P < 0.01). CONCLUSIONS: Approximately 25% more work is required to perform ACD-CPR compared with standard CPR. Both methods require subanaerobic energy expenditure and can therefore be sustained for a sufficient length of time by most individuals to optimize resuscitation efforts. Due to the slightly higher work requirement, ACD CPR may be more difficult to perform compared with standard CPR for long periods of time, particularly by individuals unaccustomed to the workload requirement of CPR, in general. PMID- 7784720 TI - Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. AB - Among all of the cathecolamines used for cardiac arrest treatment, epinephrine injection during cardio-pulmonary resuscitation is currently the most powerful means of enhancing effectiveness; however, deliberations about the optimal dosage have recently become intense. In the SAMU of Lyon (F), we conducted a double blind prospective randomized study over an 18-month period, comparing repeated standard-dose epinephrine (1 mg) and repeated high-dose epinephrine (5 mg) in the management of cardiac arrest outside the hospital. Five-hundred thirty-six patients were enrolled with 265 in the standard-dose group and 271 in the high dose group; both groups are globally similar. One-hundred eighty-one (33.8%) patients returned to spontaneous circulation (R.O.S.C.); 85 in the standard-dose group (32%) and 96 in the high-dose group (35.5%). One-hundred nineteen patients (22.2%) were admitted; 54 in the standard-dose group (20.4%) and 65 in the high dose group (24%). At 6 months nine patients (7.6%) were alive; three patients from the standard-dose group (5.5%) and six from the high-dose group (9.2%). We never noticed cardiac or neurologic adverse effects with the high doses. The results of this study are not statistically significant, but we observed a marginal trend towards repeated 5 mg epinephrine doses. A large French multicentre study is now necessary. PMID- 7784721 TI - Evaluation of outcome following cardiac arrest in patients presenting to two Scottish emergency departments. AB - OBJECTIVES: To compare and contrast outcomes following cardiac arrest managed in two Accident and Emergency departments, and to identify factors which might account for such differences. DESIGN: Prospective 1-year evaluation of patients sustaining an out-of-hospital cardiac arrest. SETTING: The Accident and Emergency departments of the Edinburgh (ERI) and Glasgow (GRI) Royal Infirmaries which serve two large urban municipalities. PATIENTS: All patients sustaining a prehospital cardiac arrest and brought to ERI or GRI were included. Children (< 13 years), those declared dead on arrival at the scene, and events related to poisoning, near drowning, trauma and pregnancy were excluded. MEASUREMENTS AND MAIN RESULTS: There were 297 prehospital arrests from ERI, and 158 from GRI. Eighty-two (27.6%) were admitted as 'in-patients' to ERI and 23 (14.6%) to GRI (P < 0.01). Thirty-nine (13.1%) survived to hospital discharge from ERI; 13 (8.2%) survived to discharge from GRI (NS). The proportion of VF/VT:Asystole observed was significantly different between the two centres--162:98 from ERI, 54:73 from GRI (P < 0.001). Significantly more prehospital arrests were witnessed and received bystander CPR in those brought to ERI (P < 0.02). For the combined VF/VT/Asystole groups the ERI ambulance response times were significantly shorter (P < 0.01). However, there was no significant difference in the collapse to EMS arrival at the scene times between ERI and GRI. Two survivors from ERI had asystole as their initial observed rhythm. From GRI, one survivor had asystole, one had electromechanical dissociation and in another the initial rhythm was unknown. No survivor to discharge had severe neurological disability. CONCLUSIONS: Patients suffering out-of-hospital cardiac arrests in Edinburgh have a significantly better chance of being admitted to a ward. There is a trend favouring better survival to discharge in Edinburgh, but with the numbers investigated this does not achieve statistical significance. Amongst those factors which contribute to survival there are fewer witnessed arrests, less bystander CPR and slower ambulance response times in those brought to GRI. There is a need to investigate the environment in which patients collapse, to train the public in CPR, and to review the efficiency and resourcing of the ambulance service. PMID- 7784722 TI - Failure of ambulance crew to initiate cardiopulmonary resuscitation. AB - The Utstein style of reporting out-of-hospital cardiac arrests requires that all confirmed cardiac arrests considered for resuscitation are analysed and that a record is made of the number of cases where no resuscitation is attempted. We report a series of 942 confirmed cardiac arrests considered for resuscitation by South Glamorgan Emergency Medical Service (EMS). There were 370 (39.3%) cases where no resuscitation was attempted by the EMS. The ages, male/female ratio and EMS response times were similar in both the group that received ambulance resuscitation and those that did not. Those not receiving resuscitation were less likely to have had an arrest of cardiac aetiology (51.3% vs. 75%, P < 0.00001). Rigor mortis or decomposition of the body was present in 50.8% of cases and in 20% a doctor had already confirmed the patient dead. In the remainder the ambulance crew failed to start resuscitation for a variety of reasons. PMID- 7784723 TI - Pre-hospital cardiac arrest: room for improvement. AB - OBJECTIVE: To audit the outcome from pre-hospital cardiac arrest managed by ambulance personnel, and to assess their proficiency by analysing the time to initiate basic and advanced cardiac life support, the compliance with national guidelines, and the overall success of resuscitation. DESIGN: A retrospective analysis of ambulance service report forms of pre-hospital cardiac arrests, where active resuscitation was attempted by ambulance personnel between October 1992 and May 1993. SETTING: The City of Salford. SUBJECTS: 100 consecutive patients who suffered cardiac arrest out-of-hospital and who were brought to the accident and emergency department of Hope Hospital alive, or with resuscitation still in progress. RESULTS: Only 4 of 100 patients were successfully resuscitated out of hospital, of whom 2 survived to leave hospital. Detailed analysis of pre-hospital performance was performed on 89 patients only, as 11 report forms were missing (no successful pre-hospital resuscitations in this 11). Ventricular fibrillation was the first recorded rhythm in 51.7%, but 85.7% were in asystole or electromechanical dissociation on arrival at hospital. No patient who was still in cardiac arrest on arrival at hospital was successfully resuscitated. 11 patients received 'bystander CPR'. The median time to basic life support was 6 min; the median call-to-response interval was 8 min; the median call-to-advanced cardiac life support interval was 21 min; the median on-scene time was 31 min (paramedics), or 15 min (technicians). The dose of drugs given by the intravenous route did not comply with the contemporary recommendations in 43.2%, and those doses given by the endotracheal route were inadequate in 37.9% of the cases. Endotracheal intubation was attempted in all paramedic resuscitations (91.4% success); intravenous access was attempted in 60.3% (91.7% success). CONCLUSIONS: The survival from pre-hospital cardiac arrest in this community is worse than the national average. There is no single explanation for this. Better community CPR training, greater efficiency at the scene through additional personnel, and stricter compliance with national ACLS guidelines, facilitated by extended refresher training, are all required if outcome is to be improved. PMID- 7784724 TI - The technique of endobronchial lidocaine administration does not influence plasma concentration profiles and pharmacokinetic parameters in humans. AB - This study investigated plasma concentration profiles, pharmacokinetic characteristics and side-effects of lidocaine following 3 different administration techniques. Sixty ASA I/II patients undergoing elective ENT operations were randomised into 4 groups. Lidocaine 1% (1 mg/kg) was administered 50 min before the end of the operation, via a regular endotracheal tube (group 1), a suction-catheter deep endobronchially (group 2), or an EDGAR-(Endobronchial Drug and Gas Application during Resuscitation)-tube characterized by a separate injection channel ending at the orifice of the tube (group 3). For the control group, a regular endotracheal tube was inserted without lidocaine administration (group 4). Anesthesia was induced with propofol (2 mg/kg), sufentanil (0.5 micrograms/kg), and vecuronium (0.08 mg/kg) and continued as total intravenous anesthesia with propofol (8 mg/kg/h) and oxygen in air (FiO2 = 0.33). A control and 13 blood samples were taken up to 180 min after lidocaine administration. Lidocaine plasma concentrations were determined using a fluorescence polarization immunoassay (TDxFLx). Heart rate, blood pressure, endtidal PcO2, and oxygen saturation were similar in all groups investigated. Ventilation was interrupted for 3.6 +/- 0.5 s in group 1 and 10.2 +/- 0.8 s in group 2, to administer lidocaine. Patients from group 3 were ventilated continuously because of a separate injection channel integrated in the EDGAR-tube. Sore throat was significantly increased in group 2 as compared with groups 1, 3 and 4. Asorption of lidocaine in groups 1-3 resulted in maximal mean plasma concentrations ranging from 0.78 to 0.85 micrograms/ml after 16.9 to 22.4 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784727 TI - [Classification of Klebsiella strains with lectins]. AB - Fourteen different plant seeds were used to obtain lectins which in turn were used to agglutinate 72 different serological strains of Klebsiella. The results were used to design a scheme which distinguishes 62 serotypes (91.6%) with a unique agglutination pattern with lectins. Two pairs of strains as well as two sets of three strains gave the same patterns. This procedure is useful as an alternative in the identification of strains for epidemiological purposes. PMID- 7784725 TI - Contribution of brain injury to hypertension following intravenously-administered pancuronium in rats. AB - Abnormal hypertension sometimes occurs following intravenous administration (i.v.) of pancuronium in patients with brain injury. The present experiment was designed to determine whether brain injury contributes to the hypertensive response of i.v. pancuronium. Forty-six Wister strain rats were studied, of which 39 had induced brain injury at (a) upper pons (b) midbrain (c) thalamus region (excluding hypothalamus) and (d) cerebellum or a combination of these sites. The injury was made by single insertion of a 22 Gauge needle through the skull surface. The quantity of pancuronium solution administered i.v. in each case was 1.0 ml containing either 0.8 mg/kg or 8 mg/kg of pancuronium. Group A (n = 7) had no brain injury and the mean arterial pressure (MAP) did not change following i.v. administration of pancuronium. In Group B (n = 9) (a+b+c, 8.0 mg/kg) MAP rose from 90.9 +/- 15.4 to 102 +/- 22.0 mmHg and in Group C (n = 7) (a+b+c, 0.8 mg/kg) MAP rose from 148.4 +/- 13.3 to 160 +/- 14.4 mmHg. In Group D (n = 5) (b+c, 8.0 mg/kg) MAP remained unchanged. In Group E (n = 5) (a, 8.0 mg/kg) MAP rose from 130.3 +/- 18.7 to 146 +/- 27.6 mmHg and in Group F (n = 6) (a, 0.8 mg/kg) MAP rose from 129.7 +/- 15.6 to 135.8 +/- 13.8 mmHg. In Group G (n = 7) (d, 8.0 mg/kg) MAP remained unchanged. Since the MAP was elevated in only those groups that received injury in the upper pons, we concluded that injury in the upper pons can lead to hypertension following i.v. administration of pancuronium. PMID- 7784726 TI - [Pseudomonas fluorescens: production of pyoverdine in human blood at 4 degrees C and cytotoxic effect of the pigment]. AB - Pseudomonas fluorescens PAB strain produced pyoverdine in a synthetic medium, this pigment was purified by solvent extraction and ion exchange, then sterilized by filtration. Where cytotoxic effect on human leukocytes was assayed, death and lysis was observed. Sublytic doses decreased leukocytes phagocytosis and chemotaxis. Bacteria grew and produced pigment in blood stored a 4 degrees C, with a pyoverdine production of 0.13 mg/ml of serum after 5 days of incubation. PMID- 7784728 TI - [Gardnerella vaginalis biotypes: modification of a proposed system]. AB - A modified scheme is proposed for biotyping Gardnerella vaginalis based on detection of hippurate hydrolysis, beta-galactosidase (ONPG) and lipase, and fermentation of arabinose, galactose and xylose. Thirty three biotypes were found among 140 strains from women with and without bacterial vaginosis (non-specific vaginitis). The distribution of biotypes were found to be significantly different, being more predominant the biotypes 1A; 5G; 7A; 7D and 7G in women with vaginosis and the biotypes 5G and 6H in women without vaginosis. These data suggest that some biotypes of Gardnerella vaginalis are associated with bacterial vaginosis. PMID- 7784729 TI - A discrete factor A is detected on Vibrio cholerae Non-O1, O:139 by laser flow cytometry. AB - A new serogroup of Vibrio cholerae non-O1, O:139, has been implicated in recent epidemics. It was scanned with a factor A-specific fluoresceine-conjugated monoclonal antibody, searching for antigen determinants by laser flow cytometry. First, a group of gram-negative 4-amine-4, 6 dideoxy-D-mannose antigen-related microorganisms were tested to assess monoclonal antibody cross reactions. Later, a clear recognition of antigen determinants was found with this monoclonal antibody, on V. cholerae non-O1, O:136, Bengal, and MO45 strains, showing no cross reactions with the antigenically related non O1, O:22, and Inaba and Ogawa O1 strains. On the other hand, factor A of V. cholerae O1 strains was recognized by the specific monoclonal antibody and a discrete factor A on V. cholerae non O1, O:139, Bengal and MO45 strains was detected. PMID- 7784732 TI - Tn1, a Tn3-like transposon present in plasmid RP1, transposes more frequently to another plasmid than to the chromosome. PMID- 7784730 TI - Biological and protective activities of outer membrane proteins from Bordetella. AB - In this work the biological properties and the capability of the outer membrane proteins (OMPs) from different strains of Bordetella to induce protection against challenge with B. pertussis 18323 were examined. The OMPs from each strain were isolated using Schnaitmann's method. Two OMPs (30 and 32 kDa) were found to be specific for the vaccine strains of B. pertussis and were absent in the OMPs preparation from both B. parapertussis and B. bronchiseptica. When the OMPs from the vaccine strains of B. pertussis were assayed in the mouse intracerebral protection test, they were found to be highly protective (75%-88%) against a challenge with 250 50% lethal doses (LD50) of B. pertussis 18323. However, no correlation was observed between the protective activity and the lymphocytosis promoting factor (LPF) content of different preparations. Moreover, neither LPF activity or histamine-sensitizing activity (HSA) were found in any of the OMPs assayed. Our results show that OMPs from B. pertussis vaccine strains play a key role in the induction of protective immunity against B. pertussis 18323 in mice, making them excellent candidates to be used in further studies for the development of a pertussis vaccine for humans. PMID- 7784731 TI - [Biological flow tracers: growth and survival of Bacillus subtilis 65-8 under environmental stress]. AB - Microbial flow tracers are presently limited to a strain of Bacillus globigii and a few highly specific bacteriophages. Bacillus subtilis 65-8 produces a black pigment as part of the primary metabolism under minimal nutritional conditions, with glucose as the sole carbon and energy source. This work shows that Bacillus subtilis 65-8 spores are thermostable (55 degrees C during 150 dias), halotolerant (they germinate and grow in an enriched medium with up to 12% NaCl), persistent in a system of sand-soil and sewage, even in the presence of added commercial oil derivatives (kerosene, leaded gasoline and unleaded diesel), they are capable to move through porous systems even as the liquids, viscous as they may be, move through. Moreover, spores were resistant to the presence of autochtonous microorganisms in sewage, where we did not detect any other organism with differential characteristics like our strain (black pigment production in minimal medium) which could interfere with the identification of our biological flow tracer. The characteristics of Bacillus subtilis 65-8 make it a suitable biological flow tracer. PMID- 7784733 TI - [Sporulation of the entomopathogenic fungi Hirsutella thompsonii Fisher and H. nodulosa petch in mixed culture]. AB - A large-scale method for producing fungal pathogens for mites, Hirsutella thompsonii and H. nodulosa in two phase culture (liquid and solid), was developed to induce conidiogenesis. The vegetative growth that was obtained in the liquid media of soy meal with shaking, from an inoculum 0.5 g wet weight equivalent to 0.1 g of dry weight, was inoculated on eight solid supports. Generally for most of the strains, the three supports yielding greater conidiogenesis were rice, barley and bran, excluding the strains whose greater sporulation is achieved in rice, oats and sorghum, sorghum and oats as compared to barley and bran, respectively. Maximum production of conidia was obtained with HtM2, HtM4481 and HtC59 strains of H. thompsonii, which reached on solid support 334.75, 269.68 and 137.12 x 10(7) conidia/g, respectively. PMID- 7784734 TI - Comparison of neuroinvasive abilities of HSV-1 and HSV-2 in mice. AB - We compared neuroinvasive properties of HSV-1 MacIntyre strain and HSV-2 G strain, after inoculation of mice by intraperitoneal, intranasal and intracaudal route, by scoring for encephalitis and death. HSV-2 was more neuroinvasive than HSV-1 by any route, since mice inoculated intranasally or intracaudally with HSV 2 required 100 fold lower dose than HSV-1 to induce encephalitis and death, which occurred earlier than in HSV-1 infected mice. HSV-2 was found in brain tissues at a lower concentration (10(1.8) to 10(2.7) PFU per 0.1 g of brain) than HSV-1. Mice inoculated with HSV-2 developed a more aggressive behavior than those inoculated with HSV-1, although they showed a lower virus concentration per gram of brain. These results showed that HSV-2 G strain was more neuroinvasive than HSV-1 MacIntyre strain and its ability to produce damage of CNS was not directly related to the amount of virus in it, and suggests that neuroinvasiveness is a complex phenomenon, which could involve viral genomic expression and evasion of the immune system. PMID- 7784735 TI - Detection of Borrelia burgdorferi DNA in human skin biopsies and dog synovial fluid by the polymerase chain reaction. AB - The polymerase chain reaction was used to amplify DNA sequences of the etiologic agent of Lyme disease, Borrelia burgdorferi, and was applied to the detection of the spirochete in humans and dogs. Oligonucleotide primers used in the reaction flank a 244-base-pair representing part of the variable region V4 of the B. burgdorferi 16S rRNA from biopsies of patients with acrodermatitis, and in synovial fluid from a dog with arthritis. These data suggest the presence of the disease in our state. PMID- 7784737 TI - [Current progress in chemotherapy for bronchial cancer]. AB - Recent progress has, as practical consequence, placed chemotherapy as the first line therapy for any type of lung cancer, except for stages I and II non-small cell lung cancers where surgery alone remains the best approach so far. Indeed, the introduction of cisplatin-based chemotherapy in front-line ("neo-adjuvant") has significantly improved in non small lung cancer the results of surgery and radiotherapy in stage III and of supportive care in stage IV, mainly in term of survival. The development of new cytostatic agents and growth factors and the evolution of therapeutic concepts have lead to multiple clinical investigations that are reviewed in both small cell and non small cell lung cancers. PMID- 7784736 TI - [Trypanosoma cruzi: influence of human plasma on the morphogenesis of blood trypomastigotes in a cell-free culture media]. AB - Morphogenesis of blood stream trypomastigotes in the cell free culture medium F69 at 37 degrees C for 10 days showed qualitative differences either with or without human plasma. Without human plasma, blood stream trypomastigotes performed only one cycle before disappearing and the culture kept growing as amastigotes and epimastigotes until the end of the experiment. In contrast, human plasma induced multiple cycles of transformation. The sequence was blood stream trypomastigotes, regressive parasites, amastigotes, progressive parasite and again trypomastigotes. Human plasma preserved the trypomastigote stage, produced a blockade of the epimastigote stage and inhibited the division of amastigotes. In this experimental model, human plasma modified the biological cycle of T. cruzi by inducing or inhibiting different stages. PMID- 7784738 TI - [Cardiovascular toxicity of anticancer chemotherapy: 5 cases treated in intensive care]. AB - During a five-months period, 5 cases of cardiovascular toxicity related to chemotherapy were observed. Various hypotheses are discussed to explain the pathogenicity of this type of toxicity. Cardiovascular risk factors may favor this toxicity. In the presence of known cardiovascular risk factors, the choice of a less toxic regimen is desirable and, if this is not possible, the patient should be treated with continuous monitoring of the vital parameters. PMID- 7784739 TI - [Exploratory laparotomy under local anesthesia]. AB - Diagnostic laparoscopy under local anaesthesia for acute pain in the right iliac fossa in an old man is reported. Exploring the abdominal cavity under local anaesthesia is an excellent method for establishing a diagnosis in doubtful abdominal pain presentation. This technically easy procedure may avoid up to 45% of unnecessary laparotomies and related complications. PMID- 7784740 TI - [Crises of public health, medicine, society?]. AB - Public health is in crisis. Apart from temporary factors, this crisis could have also its origin in theoretical and conceptual insufficiencies relative to the definition of this scientific domain. Organisational and institutional conditions needed for the strengthening of public health are discussed in relation with the localization of its production sites, taking into account the needed synthesis or consensus to reach and in view of the larger and valuable intellectual traditions to which it belongs. The crisis of public health is only part of a crisis of medicine and of our modern societies. PMID- 7784741 TI - [Complications of intrauterine devices]. AB - Abdominal migration of intrauterine devices is very rare. However, during the puerperium when the uterus is small and the uterine wall thin, the risk of perforation increases. A device removed by coelioscopy is described. PMID- 7784742 TI - [Syndrome X and general medicine]. AB - The general practitioner man be confronted with the X syndrome, which includes central obesity, impaired glucose tolerance or type II diabetes mellitus, dyslipidemia and eventually hypertension. Insulinoresistance and hyperinsulinaemia contribute to the pathogenesis of these disorders. The syndrome X, which leads to important cardiovascular morbidity, needs appropriate treatment, which has to take into account the actions of drugs on glucose and lipid profiles. Syndrome X is rarely treated as a whole, but to treat separately each of its manifestations would be a mistake. The necessity of a global approach, a complete understanding of the familial environment and also the duration of the development of syndrome X justify the prominent part of the family doctor in the follow-up. PMID- 7784743 TI - [Food deficiencies in children--multicenter survey in the school environment. Analysis of the daily diet of adolescents]. AB - The aim of this work is to study the food habits in a group of 131 children of school ages (11-14 years); they had to take notice of their food, with control by interview; results shown a shortage in calories (80% of normal supply for age), but also a severe imbalance: too many lipids, too few complex sugars, deficiencies in calcium, phosphorus, iron, iodine, vitamins A and C, fibers (30% of normal supply); alcohol has been used by 35 children. A nutritional education is recommended for this age group. PMID- 7784744 TI - [How I treat... a patient with severe or aggravated cardiac insufficiency]. PMID- 7784745 TI - [Hashimoto-Pritzker self-healing histiocytosis: a skin tumor in infants]. PMID- 7784746 TI - [Role of converting enzyme inhibitors in myocardial infarction]. PMID- 7784748 TI - [Value of the study of induced expectoration in pulmonary pathology]. PMID- 7784747 TI - [Current pharmacological approach to the treatment of locomotion disorders due to spinal lesions]. PMID- 7784749 TI - [Asialia: diagnosis--treatment]. PMID- 7784750 TI - [Endoscopy in plastic surgery]. PMID- 7784751 TI - [Sports activities and susceptibility to infection]. PMID- 7784752 TI - [Recombinant alpha 2b interferon in the treatment of chronic viral hepatitis C: comparison of 2 schemes, classical and high-dosage]. PMID- 7784753 TI - [How I manage... a type 2 diabetic patient]. PMID- 7784754 TI - [Drug of the month. Citalopram (Cipramil)]. PMID- 7784755 TI - Can running injuries be effectively prevented? PMID- 7784756 TI - The use of doubly labelled water in quantifying energy expenditure during prolonged activity. Personal observations. PMID- 7784757 TI - The relationship of hypercapnic ventilatory responses to age, gender and athleticism. AB - When a gas mixture containing carbon dioxide (CO2) is inhaled by an individual, alveolar ventilation is increased. This ventilatory response to CO2 highlights the relationship between the increase in exercise ventilation and the increase in alveolar CO2 pressure (paCO2). This response is mediated centrally by brainstem chemoreceptors in the medulla and, to a lesser extent, peripherally by the carotid and aortic bodies. However, the response of increased breathing to rising paCO2 varies markedly among individuals. The responses to CO2 rebreathing have been investigated by a variety of research groups for different reasons. The range of responses by children and adults including: gender differences; responses by athletes; the relationship between age and body size; and whether it is an acquired or inherited response have been studied. The following is a summary of these different aspects of CO2 rebreathing has been complied to assist researchers studying any single or multiple facets of the area. PMID- 7784758 TI - Applied physiology of ice hockey. AB - Today's elite hockey players are physically bigger and have improved levels of physiological fitness when compared with their predecessors. Correspondingly, previous ice hockey studies that have become widely referenced may have little relevance to current players and the way the game is presently played. A great need exists to apply exercise science to the game of ice hockey. Although much has been written about the physiology of ice hockey, there is little information based on well controlled studies. Particularly, there is a paucity of knowledge concerning optimal training schedules, training specificity, recovery profiles and seasonal detraining. Moreover, the reports that do exist have attempted to make comparisons across all levels of skill and talent. Thus, fundamental questions remain as to actual physiological exercise response and specialised training programmes for ice hockey players, particularly at the elite level. There is a demand for new properly designed experiments to find answers pertaining to the appropriate training methods for today's ice hockey players. Future research directions should consider the relationships between performance and such variables as neuromuscular skills, strength, power, peripheral adaptations, travel, hydration, detraining and sport-specific training programmes. Incidence and severity of injury among ice hockey players in relation to fatigue and fitness must also be investigated. Much of the information currently used in ice hockey will remain speculative and anecdotal until these studies are conducted. PMID- 7784761 TI - [What is your diagnosis? Scar of the lower and anterior wall in coronary heart disease]. PMID- 7784759 TI - Isokinetic eccentric exercise. AB - The development of active isokinetic dynamometers has allowed the assessment of muscular moment under eccentric activations that have different characteristics to concentric actions. It is well documented that at a given angular velocity the eccentric moment is greater than the corresponding concentric moment. The moment velocity relationship under eccentric conditions has been investigated, with conflicting results. Particularly, eccentric moment was reported to remain similar to, or to increase or decrease with, increasing angular velocity. As with concentric actions, the reliability of isokinetic eccentric measurements is influenced by a number of factors such as gravity, preload force and testing position. The velocity-specific effects of eccentric training have not been extensively investigated. Based on current knowledge, eccentric exercise does not appear to be velocity-specific. Although the mode specificity of both concentric and eccentric exercises have been investigated, the resultant observations are conflicting. Eccentric training has been found to improve both concentric and eccentric strength: yet, it has also been reported to improve only concentric or eccentric strength. The reciprocal muscle group ratios under eccentric actions were found not to be influenced by angular velocity, but the significant role of the eccentric/concentric moment ratio of each muscle has not been examined thoroughly. It is well documented that eccentric activations are associated with delayed muscle soreness and muscle damage. A limited number of studies have reported that isokinetic eccentric efforts may result in a lower amount of muscle soreness compared with other exercise modalities. Isokinetic dynamometers provide some unique characteristics for rehabilitation applications. Examination of the clinical application of eccentric exercise is limited. Consequently, the use of this exercise modality in prevention and assessment of musculoskeletal injuries should be investigated further. PMID- 7784760 TI - Syncope in athletes. AB - Syncope is a brief sudden loss of consciousness and muscle tone secondary to cerebral ischaemia, inadequate oxygen or glucose delivery to the brain. The causes of syncope may be benign and require very little in the way of evaluation or treatment. However, syncope may be the harbinger of sudden death, and extensive evaluation, monitoring and detailed recommendations regarding advisability of participating in sports should be reviewed with the patient. The history is the most important clue when attempting to identify which patient with syncope is at risk for sudden death. A careful cardiac and neurological examination should be performed in any patient presenting with syncope. Selective use of laboratory testing and cardiac monitoring may assist the practitioner in making the diagnosis. Most often patients with syncope will have a benign cause such as vaso-vagal events, hyperventilation or orthostatic hypotension. Patients with a cardiac condition causing their syncope are at increased risk for sudden death. The ominous, cardiac-related causes of syncope in the younger population include hypertrophic cardiomyopathy, aberrant coronary arteries and aortic dissection secondary to Marfan's syndrome. In the older athletic population, coronary atherosclerosis may present with syncope. Dysrhythmias may be the cause of syncope in both populations. PMID- 7784762 TI - [The most dangerous drug in patients over 70 years old]. PMID- 7784763 TI - [Adult patients with congenital heart diseases: Berne statistics]. AB - Data of the 272 adult patients with congenital heart disease followed up in our department are analyzed. We emphasize the lack of reliable statistical surveys of this group of patients at the present time. The need for better intra- and interdisciplinary cooperation, specially between referring physicians and tertiary centers, is stressed. PMID- 7784764 TI - [Hypertrophic osteoarthropathy as indicator for bronchial carcinoma]. AB - Clubbing of the fingers and periosteal bone formation are the typical signs of hypertrophic osteoarthropathy, which mostly is a secondary manifestation of an underlying disease. Reporting a case of hypertrophic osteoarthropathy in association with bronchial carcinoma, we stress the importance of an extensive diagnostic evaluation with chest X-ray as a first step. PMID- 7784765 TI - [Possibilities in psychiatric-psychotherapeutic and family practice treatment of borderline patients]. AB - In this article it is shown that, in spite of the diagnostic heterogeneity and in spite of differing concepts for treatment, basic principles for treatment may be assessed that have proven effective in daily therapeutic routine. It is decisive to consider typical difficulties in which therapists of borderline patients may get involved. Treatment is primarily based on psychotherapy. After a short review of different therapeutic concepts for borderline derangements, fundamental psychotherapeutic principles are illustrated. According to target symptoms, psychotropic drugs may be indicated as an adjunct. The use of various drugs is discussed. Ambulatory and clinical options for treatment and their indications are summarized, and treatment of borderline patients by their family doctor is stressed in particular. PMID- 7784766 TI - [Circumscribed skin necrosis following intramuscular injection (embolia cutis medicamentosa)]. AB - Among the local complications following the intramuscular injection of therapeutic drugs, the syndrome of 'embolia cutis medicamentosa' deserves special attention. Shortly after the intramuscular injection, the patients notice severe pain and an erythematous discoloration of the skin at the injection site, followed by central demarcation and a sharply circumscribed skin necrosis with or without damage to peripheral nerves. We report about three patients, two of which had to be hospitalized. The drugs injected were combinations of analgesics of the phenylbutazone-type, corticosteroids, local anesthetics and cyanocobalamin. The observation that this severe complication may be associated with technically proper ventrogluteal injection of a wide array of therapeutic drugs shows that intramuscular injections require valid indications. PMID- 7784767 TI - [A case from practice (325). 1. Strongyloidiasis--reactive arthritis. 2. Anemia in multiple helminth infestation. 3. Essential hypotension]. PMID- 7784768 TI - [Psoriasis: diagnosis and therapy]. AB - The pathogenesis of psoriasis is not fully understood, but two mechanisms seem important, i.e. epidermal proliferation and an inflammatory process. Among these, the cytokines production and the expression of adhesion molecules, are the most important. To make an exact diagnosis of psoriasis it is essential to have the case history and the clinical findings. In difficult cases it might be necessary to make a biopsy. If the patient has not been treated, the histopathology is very characteristic. There are two main possibilities for treatment: either local therapy or internal therapy. Local treatment usually starts with the treatment of keratotic plaques, mostly by baths (salt or sulphur), followed by ointments or oils containing salicylic acid 5% or 10%. After a couple of days a specific local treatment is started. In the clinic or in a day care center one might use the classical therapeutic modalities such as dyes (Castellani) or tar or dithranol preparations. The inconveniences of these modalities are that they either color the body or the textiles or that they smell. These preparations, especially in combination with UV light, are very effective and useful. On an outpatient basis corticosteroid preparations are mostly used, but in certain skin areas they might provoke skin atrophy. With the development of the vitamin-D derivative calcipotriol, further progress has been achieved. This preparation is not colored, does not smell and is not followed by atrophy. The efficacy of calcipotriol is similar to potent corticosteroids. Calcipotriol can very well be combined with UV therapy. UV therapy modalities consist in solar light therapy (sea shore or mountains), UVB phototherapy, SUP therapy, or PUVA therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784769 TI - [Surgical diseases in the inguinal area in children]. AB - This outline describes the diagnostic and prognostic factors as well as the operative procedures based on the experiences made at the University Clinic for Pediatric Surgery, Zurich. Focused on practical work, the most frequent congenital, acute and chronic affections are described with respect to differential diagnostic characteristics. PMID- 7784770 TI - [Practice-oriented treatment of depression today]. AB - The modern treatment methods which are relevant for everyday practice are summarized, and their application is discussed based on an integrative depression model. The biological and psychosocial therapeutic methods can be complementary, if the actual stage of illness is taken into consideration. An antidepressive medication is needed, especially in severe depressive episodes. The application of some simple rules can assist in the choice of antidepressive medication. But also the employment of sound principles for the psychosocial treatment of depressive patients is recommended. PMID- 7784772 TI - [What is your diagnosis? Hypertrophic cardiomyopathy]. PMID- 7784771 TI - [Current treatment concepts in patients in the acute stage of subarachnoid hemorrhage due to rupture of an intracranial aneurysm]. AB - Subarachnoid hemorrhage (SAH) due to rupture of intracranial aneurysm constitutes almost 10% of all strokes and is a neurosurgical emergency along with head injury and intracerebral hemorrhage. Accurate diagnosis and surgical intervention without time loss are the key factors for successful treatment. Almost 40% of the patients with SAH already die or are in a moribund status at the first bleeding before hospitalization, the rest of the patients (60%) can be transferred to hospitals for further treatment. The factors determining prognosis of SAH involve a direct initial injury to the brain at the time of the rupture, a high rebleeding rate in the acute stage, development of cerebral vasospasms, and hydrocephalus due to stasis of the cerebrospinal fluid. Surgical intervention is intended to eliminate these factors as much as possible. Perioperative intensive medical care in combination with the surgical intervention is essential to achieve best outcome from the surgical treatment. The aim of this article is to make a short review over SAH and to give a current concept of therapy in the acute stage of SAH. The results of treatment of SAH in our institute are also presented and discussed. PMID- 7784773 TI - [Diabetic nephropathy: course, therapy and prevention of a serious complication]. PMID- 7784774 TI - [The borderline patient. Diagnosis, psychodynamics and physician-patient relation]. AB - 'Borderline' is a popular psychiatric diagnosis. The uses of the term are variable and often unclear. It is the goal of this presentation to elaborate a borderline concept for use in daily clinical practise. First, development of the term over the preanalytical, analytical and empirical areas is summarized. Next, the term of borderline for clinical practise is developed on the basis of characteristics and the global picture. Characteristics are: intensive, instable behaviour in relations, reduced control of impulse, disturbed affection and mood, psychotic manifestations, instable social adaptation. Diagnosis is founded on exploration of characteristics and on seizing of the global picture. The combination with other psychiatric disorders and separation from other personality disorders have to be considered with respect to differential diagnosis. The descriptive diagnosis has to be complemented from a psychodynamic point of view. The borderline patient has in his psychologic development failed to segregate sufficiently from his primary reference person. This results in a structural deficit and a weak ego. This latter is characterized by deficient integration and deficient separation, by disturbed perception of reality and by a non-specific general weakness of the ego. Finally, difficulties arising in the relations between physician and borderline patient are outlined. PMID- 7784775 TI - [The Sentinella reporting system in Switzerland exemplified by pertussis monitoring from 1991 to 1993. Sentinel Work Group]. AB - Since 1986, 150 to 180 general practitioners, internists and pediatricians in private practises have reported morbidity data to the Swiss Federal Office of Public Health within the Sentinella network. Data on a certain number of infectious diseases, some noninfectious diseases and other reasons for consultation are collected through this reporting system. The number of participating physicians corresponded to 2.3 to 3.1% of all family practitioners for each of the three specialties. They also covered approximately 2.7% of the total annual number of consultations in Switzerland. In 1992/93, all cantons and all half-cantons except Nidwalden and the two half-cantons of Appenzell were represented by at least one physician who reported during 75% or more of the total reporting period. When compared to other countries, the network density of the Swiss Sentinel network is high. Since 1986, several infectious diseases have been continuously monitored by the Sentinella system (measles, mumps, rubella, influenza). Surveillance of pertussis, which was started in 1991, will be continued for several years. According to these data, an annual pertussis incidence rate of 60 out of 100,000 population and 100 out of 100,000 population was estimated in 1991/92 and 1992/93, resp. More than 55% of cases were children aged between one and eight years. Of these children, 70.4% were reported to be vaccinated, and 62.6% had a well-documented vaccination status (based on a vaccination certificate). In 95.6% of these cases, at least three vaccine doses were given.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784776 TI - [Disulfiram in the treatment of alcoholic patients]. AB - In a retrospective investigation we report our experience with alcohol-dependent patients who were hospitalized between 1987 and 1990. There were 58 patients, 29% of them were hospitalized several times. In the middle of 1991 and 1992 we interviewed the family doctors and the social workers who cared for the patients. In 48% of the patients there was improvement, in 24% there was a stabilization, and in 28% we noted a deterioration. There was no difference in patients treated by the family doctor alone or in patients treated by the social workers. Comparing patients taking Disulfiram with patients taking no drug, there was no difference in improvement (48% versus 50%). But the good results in patients not taking disulfiram were nearly exclusively noted for those who had been hospitalized in a special clinic for alcohol-dependent persons. Patients who were hospitalized several times for alcohol withdrawal had a worse chance to improve their situation (-20%). The therapy with disulfiram in alcohol-dependent patients is helpful to cure chronic alcoholics. Programs in a specialized clinic improve also the chance to be cured of the addiction. PMID- 7784778 TI - [A case from practice (326). Dysentery (inflammatory diarrhea, cause Campylobacter jejuni]. PMID- 7784779 TI - [HIV seropositive pregnant women from black Africa seen at the Guy de Lorier maternity unit of Tenon hospital. Report of 33 cases]. AB - There were 5503 deliveries between 1989 and 1991 in the Guy de Lorier Maternity Unit (Pr Salat-Baroux) of Tenon Hospital, Paris. These included 81 women testing HIV+ in the department with 33 asymptomatic black African women among 781 deliveries. Africans account for 14% of women delivered in the department but for 40% of seropositives in the unit, with a predilection for women from Zaire (central Africa), accounting for 17 seropositives. They only represent 50% of all cases of African HIV+ and 20% of the unit, while they account for only 6% of the black African community and 0.8% of the maternity unit. Women from west Africa accounted for 45.5% of African seropositive cases, with Ivory Coast in first place with 24.3% while only 9% of women from Mali, accounting for 40% of African patients and 5% the units, tested positive (3 cases out of 309 patients). The mean age of seropositive patients was 23 +/- 4, pregnancies proceeded normally and there were 4 therapeutic abortions. There were 9 births by cesarean section, with no evidence of neonatal contamination, the same applying in the other 20 vaginal deliveries. Routine testing (informed consent) for HIV in these high-risk (endemic zone, drug addiction) or unrecognised seropositive patients is important whenever the opportunity presents itself (prenuptial examinations, prenatal visits, family planning, preoperative assessment) in order to attempt to lower infection rates and ensure the best possible care for mother and child when there is a wish to continue the pregnancy, but also to protect hospital staff from the risks to which they may be exposed. PMID- 7784780 TI - [Basedow's disease and pregnancy in a black African population. Epidemiology and interrelations in 51 pregnancies]. AB - Forty one patients with 51 pregnancies form the basis of this study of etiological factors and reciprocal effects of pregnancy and thyrotoxicosis. Pregnancy influences the course of thyrotoxicosis and may modify its diagnostic aspects, clinical course, variations in laboratory parameters and treatment. The effect of thyrotoxicosis on pregnancy may lead to abortions, premature labour and/or toxemia. It may sometimes influence the products of conception. The essential point appears to be to seek the minimal dose of antithyroid drug capable of controlling thyroid disease without impairing fetal thyroid function. PMID- 7784777 TI - [Chest pain, dyspnea, syncope]. AB - We report about the history of a 53-year-old female who suffered from dyspnea as well as leg and chest pain for six months; in addition she experienced two syncopal events. Recurrent pulmonary embolism was suspected, which was subsequently confirmed by positive scintigraphical findings. Acute cor pulmonale may have caused the syncopes. Therapy with heparin and oral warfarin was started. Within few days the patients condition improved markedly. Signs of pulmonary hypertension disappeared within five months. PMID- 7784781 TI - [Anemia and pregnancy. Epidemiologic, clinical and prognostic study at the university clinic of the Ignace Deen Hospital, Conakry (Guinee)]. AB - Our intentions were to determine the incidence of the association of anemia and pregnancy, to evaluate maternal and fetal prognosis and to offer some recommendations regarding national health care policies. This prospective study lasting 30 months included all cases of anemia and pregnancy detected by clinical and laboratory examinations. Thus 13,191 women were enrolled in the study but only 1408 cases of anemia and pregnancy (10.67%). Primipara and grand multipara were particularly at risk. Severe forms of anemia and pregnancy were encountered often (51.71%). Maternal and fetal prognoses were very poor. Maternal mortality was 852/100,000, accounting for 65% of the maternal mortality of the department. The stillborn rate was 50 per thousand. This is a serious health problem which needs to be dealt with by a national health education programme. PMID- 7784782 TI - [Role of iron deficiency in anemia in pregnant women in Mali]. AB - The epidemiological characteristics of iron deficiency anemia after radioimmunoassay of serum and erythrocyte ferritin were evaluated in 209 Malian women at the time of delivery in a maternity unit in Bamako, Mali. The incidence of iron deficiency anemia was high (36.8%). This incidence did not reflect socio economic status, nor even any particular obstetric history, but was significantly higher in younger mothers (aged under 26). The severity of anemia was such that 2.4% of women would require a blood transfusion post-partum. It looks therefore desirable, in Mali, to screen routinely and to ensure the prevention of iron deficiency in adolescent girls and to include, in the prevention of anemia of pregnant women, routine iron supplements from the beginning of pregnancy. PMID- 7784783 TI - [Determinant factors in the choice of site of delivery and the role of peripheral maternity units in a semi-urban environment in Tunisia]. AB - The authors analyse, in the context of a developing country, a number of factors which can determine the choice of site of delivery in a population with access to several possibilities. The role of peripheral (or local) maternity units is considered in particular, in view of the utilisation problems which they raise. This leads to the conclusion of a degree of irrationality in the choice of health care services and the characteristics of women interacting with those of professionals when explaining the choice of site of delivery. Better management of available services is desirable in order to render peripheral maternity units more useful, and improve the medical performance at the time of delivery. Sensitization of the public and above all of health professionals nevertheless remains essential. PMID- 7784784 TI - [Fetal risk factors in twin pregnancies. Critical analysis of 265 cases]. AB - The authors report their critical analysis of perinatal mortality concerning 265 twin pregnancies collected between 1982 and 1993 in the Maternity Unit of the Yaounde (Cameroon) Teaching Hospital Group. There were a total of 14,277 deliveries during this period. The twin pregnancy rate was 1.8 per cent. Delivery was spontaneous in 89.6 per cent of cases and by cesarean section in 10 per cent of cases. In 3 cases the second twin was delivered by section after spontaneous delivery of the first twin. Perinatal mortality evaluated at 6.9 per cent (37 cases) was analysed according to fetal risk factors such as gestational age, type of delivery, fetal presentation, birth weight, birth rank and the time interval between birth of the first and second twin. Perinatal mortality of premature twins with 25 fetal deaths accounted for approximately 2/3 of the fetal deaths in this series. Twenty-two cases of fetal deaths seen in the group of second twins accounted for more than half of all fetal mortality. The time interval between the two births was an important factor in the fetal prognosis of the second twin. There were 14 cases of death of the second twin for a time interval longer than 20 minutes as compared with 8 fetal deaths for an interval of 20 minutes or less. Breech presentation was associated with abnormally high fetal mortality (16 cases). Our conclusion is that improved perinatal mortality in twin pregnancies must be sought by preventing prematurity. Breech presentation is a factor of poor prognosis, in which it is important to widen indications for prophylactic cesarean section aimed at improving fetal prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784785 TI - [Coexistence of a partial hydatiform mole and a viable twin pregnancy. A case seen at the Sokode regional hospital (Togo)]. AB - A case was seen of partial hydatidiform mole coexisting with a viable twin pregnancy. Apart from prematurity which created early problems in caring for these girls twins, born with a good Apgar score and birth weights of 1400 g and 1350 g, the outcome was satisfactory for both the mother and daughters, who thrived marvelously. The incidence of this clinical form of trophoblastic disease which is 1/10,000 deliveries in our series confirms it rarity as reported by many authors. PMID- 7784786 TI - [Uterine rupture during labor. Report of 106 cases at the Maternity Center of Tunis (Tunisia)]. AB - This study involves 106 cases of the uterus seen at the Rabta Maternity and Neonatology Center (Tunis) over a period of 6 years. The incidence was 1.51% of labors and 75.4% of cases involved rupture of a scarred uterus. Rupture of a healthy uterus accounted for 24.6% of cases. The clinical picture was asymptomatic in 66.25% of cases involving a scarred uterus. Treatment of rupture of the uterus was essentially conservative by suture of the tear (73.6%). Maternal mortality was 2.8%. Perinatal mortality was high at 37.7%. PMID- 7784787 TI - [Endoscopic gynecologic surgery in Africa. Luxury of necessity?]. AB - Per- and postoperative mortality remain high in black Africa, with rates of the order of 30 to 40% according to teams. Three essential causes are generally reported: infection, hemorrhage and anesthetic complications. There can be no doubt as to the advantages of celiosurgery over open surgery: low postoperative morbidity, less than 1% serious complications, real savings in treatment costs by shortening of average hospital stay and time off work. Celio-surgery is technology-dependent and operator-dependent. The cost of equipment remains prohibitive and its maintenance delicate and expensive, potentially hampering the implantation and spread of this new technique in Africa, which also lacks specifically trained staff as well as an appropriate technical infrastructure. Nevertheless, the experience of teams in Cameroon and Gabon are encouraging with 110 and 220 patients respectively treated by celio-surgery without complications. A veritable journeyman-apprentice approach is necessary for the learning of these new techniques by teams in developing countries, in several possible ways (locally or abroad), in order that the population as a whole can enjoy the benefits of the reproducible therapeutic and diagnostic advances of new techniques (celio-surgery, MAP, antenatal diagnosis, medical imaging). PMID- 7784788 TI - Prevalence of septal deviations in school-aged children. AB - A total of 687 school children, aged 6-15 years, were examined for nasal septal deviations with anterior rhinoscopy and maxillary sinus radiography. Septum deviations were divided into four different categories and the final evaluation included the clinically significant deviation, based on purely morphological findings. Columella deviation was an exceptional condition in 0.7% of children, septum spurs were found in 3.8%, bending of the quadrilateral cartilage was present in 13.4%, and premaxillary luxation in 28.7%. A clinical diagnosis of septum deviation was made in 9.5% of children. The occipitomental projection of the maxillary sinus X-ray was a good diagnostic tool in evaluating the clinical significance of septum deviation. PMID- 7784789 TI - A comparison of budesonide nasal dry powder with fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis. AB - There is circumstantial evidence that the incidence of allergic rhinitis is becoming increasingly common. There may also be a need for more potent drugs with minimal local and systemic side effects. This study has compared the efficacy and safety of budesonide delivered as nasal dry powder with fluticasone propionate aqueous nasal spray in the treatment of perennial allergic rhinitis. Ninety-eight patients participated in a randomized, parallel group and partly blinded study. Treatment consisted of budesonide dry powder (Rhinocort Turbuhaler) at once daily doses of 200 micrograms (n = 24) or 400 micrograms (n = 22), fluticasone propionate (200 micrograms) once daily (n = 25), and placebo for budesonide dry powder (n = 27). A six-week treatment period was preceded by a two-week baseline period without treatment. Efficacy was assessed by daily subjective scoring of nasal symptoms. Safety was assessed by rhinoscopy, analysis of urine cortisol, and questioning of adverse events. All active treatments were significantly superior to placebo in controlling nasal symptoms. No significant differences in efficacy were found between the two budesonide regimens and fluticasone propionate. Adverse events were few and minor, and non-significantly distributed between treatments. In conclusion, this study shows that budesonide dry powder administered from Turbuhaler (200 or 400 micrograms) and fluticasone propionate aqueous spray (200 micrograms) administered in once daily doses, are effective and safe treatments of perennial allergic rhinitis. These novel treatments may enhance the current available alternatives in clinical practice. PMID- 7784790 TI - Effects of inflammatory mediators on ciliary function in vitro. AB - Prostaglandins and histamine released during inflammatory and allergic reactions can affect the mucociliary system in different ways. By studying the effect of these mediators on ciliary beat frequency (CBF) with a photo-electrical technique in airway explants from different species, i.e. guinea-pig trachea, rabbit maxillary sinus, and human adenoid, the mechanisms underlying the effects of prostaglandin and histamine were further elucidated. Prostaglandin E1 (PGE1) produced a modest increase in CBF in preparations from guinea-pig trachea. The maximum response was 12.9 +/- 3.4% for the dose of 0.1 micrograms/ml, corresponding with 0.28 microM. Prostaglandin E1 produced a dose-dependent increase in explants from rabbit maxillary sinus, the maximum effect was 35.9 +/- 14.1% at a dose of 1.0 micrograms/ml. PGE1 produced a lesser increase in CBF in explants from human adenoids. A maximum increase of 4.1 +/- 1.6% was observed at a dose of 0.1 mg/ml. Histamine produced a moderate increase in CBF in explants from human adenoid at concentrations of 0.01-0.1 mM, corresponding with 1.84-18.4 micrograms/ml. In contrast, histamine did not significantly alter CBF in explants from the rabbit maxillary sinus or guinea-pig trachea. These results indicate that there are interspecies differences in the responsiveness to prostaglandins, and that PGE1 seems to have more powerful effects on CBF in the upper than in the lower airways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784791 TI - New aerodynamic aspects of nasal patency. AB - In considering possible aerodynamic indicators of subjective nasal stuffiness, we measured nasal resistance, acceleration change of nasal airflow, and alteration of differential pressure and compared those with the degree of severity of sensation of nasal obstruction in 75 patients. The acceleration change of airflow and alteration of differential pressure are presented as an equation: y = ax2 + bx + c, in which "a" represents the approximate shape of the curve. Nasal resistance, on either inspiration or expiration, and coefficient "a" of acceleration change the rapid phase from inspiration to expiration correlated well with subjective nasal patency, while coefficient "a" of acceleration change the rapid phase from expiration to inspiration and alteration of differential pressure either the rapid phase from inspiration to expiration or from expiration to inspiration did not correlate well with perception of nasal blockage. It seems that measurement of respiratory acceleration of airflow of quiet nasal breathing is a useful indicator of subjective nasal patency. PMID- 7784792 TI - Suture tip plasty. AB - The three main characteristics of the nasal tip are projection, rotation, and contour. During rhinoplasty the surgeon will strive to preserve or change these characteristics in a predictable fashion, avoiding undesirable sequelae, even after long-term follow-up. Conservation, relocation and augmentation rather than reduction are key principles in modern rhinoplasty, i.e. for obtaining gratifying tip surgery. Interdomal suture, transdomal suture, and lateral crural steal follow these modern principles, while having their clear indications for different nasal tip pathology. All three types of techniques involve (semi )permanent sutures to change the shape of alar cartilages and can be considered complementary. Based on the same surgical philosophy these three techniques can be captured with the term "suture tip plasty". The objective of this paper is to describe, in a retrospective fashion, a series of 112 patients in whom suture tip plasty has been used as part of the rhinoplasty procedure. The technique proved versatile with predictable results and few manageable complications. PMID- 7784793 TI - Modified midfacial degloving. A practical approach to extensive bilateral benign tumours of the nasal cavity and paranasal sinuses. AB - Midfacial degloving is a well-known technique for entering the nasal and paranasal cavities, the rhinopharynx and the base of the skull. We report our experience with a modification of midfacial degloving, applied to two patients with extensive bilateral benign tumours in the nasal cavities and the paranasal sinuses. No rhinoplastic procedure is necessary in this modification, and the access to the upper part of the nasal cavity is improved. PMID- 7784794 TI - Chronic nasal obstruction in children. A fiberscopic study. AB - In this prospective study, fiberscopies were gently performed in 375 paediatric patients. The purpose of the study was to evaluate the nasal and nasopharyngeal anatomy and aetiologies of chronic nasal obstruction using fiberoptic examination in children. The essential advantage of this examination is that it allows a more thorough inspection of these cavities. The authors demonstrated that there exists a significant relationship between the relative size of the adenoid tissue and nasal obstruction complaints in children (p < 0.001). When the presence of adenoid hypertrophy was confirmed endoscopically, surgery proved to be highly efficacious in relieving chronic nasal obstruction. PMID- 7784795 TI - Sphenochoanal polyp in children. Diagnosis and treatment. AB - Two cases of sphenochoanal polyp (SCP) in children are reported. SCPs originate in the sphenoid sinus cavity, and extend into the choanal via the ostium. Symptoms associated with the syndrome include nasal blockage and headaches. Endoscopical examination reveals the presence of a choanal polyp, and the sphenoid origin of the polyp can be determined by CT scan. In cases where the middle meatus is obstructed, an opacity of the maxillary sinus is often observed. SCPs cannot be distinguished from antrochoanal polyp (ACP) by histological means. The treatment of the SCPs involves surgical removal and enlargement of the sphenoid sinus ostium. Ignorance surrounding the existence and the treatment of this syndrome may result in insufficient treatment and the consequent recurrence of the disorder. PMID- 7784797 TI - Giant sphenoid sinus. A case report. AB - A rare case of giant sphenoid sinus with excessive pneumatization is presented. The relevant literature is discussed. PMID- 7784796 TI - Aspergillosis of the paranasal sinuses. AB - Aspergillosis of the paranasal sinuses is a well-established clinical entity which has recently been classified into non-invasive and invasive forms with distinct sub-divisions of both types. Two cases are described, both highlighting potential serious complications of the disease as well as the importance of adequate medical and surgical treatment in effecting a favourable outcome. The disease is reviewed and the question as to whether cases necessarily fall into previously-defined clinical and pathological categories is also discussed. PMID- 7784798 TI - Noninvasive polygraphic cardiac changes in daunorubicin-induced cardiomyopathy in rabbits. AB - The use of anthracycline antitumour agents (e.g., adriamycin and daunorubicin) is limited by their dose-related cardiotoxicity. The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 11 weeks)) were investigated in rabbits in vivo from the point of view of the occurrence of cardiotoxicity and compared with a control group of animals. Noninvasive polygraphic records (in ketamine anaesthesia, 50 mg/kg i.m.) were used for the measurement of systolic time intervals (especially the PEP:LVET ratio) to evaluate the function of the heart. The administration of daunorubicin induced a significant, progressive increase in the PEP:LVET ratio (0.3775-0.9473) and in the PEP:LVETcorr. ratio, as well as a lengthening of the preejection period PEP and a shortening of the left ventricular ejection time LVET without significant changes in the electromechanical systole Q-2. The values in the daunorubicin group were mostly significantly different from the control group of animals. The results of polygraphic records reflect thus a presence of cardiac dysfunction on the basis of daunorubicin-induced cardiomyopathy. It is thus possible to conclude that the results obtained in the study confirm the adequacy of the rabbit model of daunorubicin-induced cardiomyopathy and the methods used in the study. PMID- 7784799 TI - Treatment of intoxication with GV compound in laboratory rats. AB - Changes of some physiological functions in rats were studied following intoxication with new type of highly toxic organophosphate GV [2 dimethylaminoethyl-(dimethylamido)-fluorophosphate] in doses of 2x and 4x LD50 i.m. The intoxication has begun with increasing motoric activity followed by increased salivation, rumination and bristling. Tachypnoe and fasciculations followed by convulsions and death were observed later. Therapy of intoxication with GV compound (in dose of 2x LD50) in rats demonstrated the best antidotal effect of combination of benactyzine, atropine and HI-6. In GV intoxication in higher doses (4x LD50), therapeutic efficacy (survival of experimental animals) was limited for 24 hours. HI-6 can be therefore considered as potentially universal reactivator for the treatment of nerve agents intoxication. PMID- 7784800 TI - Teaching programs for medical biophysics: the frequency analysis. AB - Teaching programs and possibilities of creating them are discussed. A teaching program the Frequency Analysis written in the C++ language is described. Principle of harmonic analysis and FFT is explained. PMID- 7784801 TI - The immunofluorescence evaluation of some subepidermal bullous diseases by use of NaCl-split skin. AB - Authors described the results of immunohistological investigation in 13 patients- 12 with clinical diagnosis of bullous pemphigoid and 1 patient with clinical diagnosis of epidermolysis bullosa acquisita. 1 M NaCl solution was used to split normal human skin, used as substrates for immunohistological testing of the antilamina lucida and anti-sublamina densa antibodies. PMID- 7784802 TI - Examination of sensory nerve fibers by needle recording in the carpal tunnel syndrome; use of the orthodromic method with special attention to the paresthetic forms. AB - The authors examined clinically, by EMG and by electrostimulation the motor and sensory fibers of the median nerve in 15 control hands (group A), 35 hands with the paresthetic form of CTS (group B), and 33 hands with CTS and pathologic DML (group C). The examination of the sensory fibers was performed on the first (thumb) to 4th digits separately by the orthodromic technique with monitoring the NAP by needle electrodes from the wrist. Two hundred fifty six responses were averaged out and always 4 stimulatory values were followed on the sensory fibers. The highest percentage of pathologic values by DSL in group B was on the first digit (thumb: 37%), in group C on the 3rd digit (93%). By DSCV the highest number of pathologic values in groups B and C was on the thumb (43 and 90 per cent respectively), for NAP duration in groups B and C on the third digit (26 and 60 per cent respectively). In the controls the mean amplitude of NAP fluctuated between 19-50 uV. The best parameters are considered: the DSL, DSCV, somewhat less the duration of NAP. In the paresthetic form of CTS pathologic values of sensory parameters fluctuated between 8.6-42.8 per cent, in the group with pathologic DML in the range of 24.2-93.3 per cent. If one considered pathologic an examination that had at least one pathologic sensory parameter at least on one digit, group B yielded 77 per cent, and group C 100 per cent of pathological results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784803 TI - Long-term results of scleroplasty operations in children. AB - The authors refer results of 773 scleroplasty operations performed in 411 children, mean age was 11.3, S.D. 3.6 years. Irradiated human sclera proved to be the best material for scleral reinforcement. Mean myopia progression was 0.26 D/year in myopia progressiva and 0.23 D/year in myopia gravis. Mean visual acuity was better in all intervals after surgery (p = 0.0000 one and four years after, 0.0002 six years after in myopia progressiva, in the same intervals in myopia gravis it was 0.0009, 0.0027, 0.0002). Scleral reinforcement can positively influence myopia progression. PMID- 7784804 TI - Conservative surgery for renal cell carcinoma--indications, technique and results. AB - At the Department of urology in Hradec Kralove between 1989-1993 287 patients with a tumor of the kidney were operated on, in 45 of them (15.6%) conservatively. In this set there are 29 men and 16 women with the mean age 56.5 years. In 29 patients the contralateral kidney was normal (64%), 5 patients underwent nephrectomy for renal cell carcinoma, in 9 patients the opposite kidney was hypofunctionalised (hydronephrosis, cysts). In two patients the conservative approach was used for reasons of another type of malignancy (haematological). In 33 (73.3%) patients enucleation, in 12 patients resection of the lower or upper pole were done. The tumor was classified as T 1 stage in 6 patients, but in 4 patients already as T 3a (in patients with imperative indication). In 35 patients the tumor was moderately differentiated, in two ones with histologically confirmed renal cell carcinomas the tumors were poorly differentiated, in 8 patients there were histologically adenomas, in one angiomyolipoma and in another case scar after PCN (percutaneous nephrolithotomy). Preoperative examination included immunological examination, this was not done in two patients. Good results were obtained in 21 patients (60%), 12 patients were in high risk and 6 of them received immunotherapy. As an early complication one patient had urinary fistula, which resolved after introduction of stent. Relapse of malignancy in the screening period was not noticed. PMID- 7784805 TI - Low prevalence of anti-HCV antibodies among Italian Air Force recruits. AB - In 1990, the prevalence of antibodies to hepatitis C virus (anti-HCV) was assessed among 4,978 Air Force recruits aged 18-26 years coming from all regions of Italy. Positivity to anti-HCV was found by both IIIrd generation EIA and RIBA in 24 (0.48%) study participants. The prevalence was twice as high in Southern Italy and the islands as in Northern and Central Italy (0.76% vs. 0.35%), a difference which was not statistically significant. The results of multiple logistic regression showed that no sociodemographic variable (region of birth, father's years of education, number of siblings) was associated with anti-HCV positivity. No anti-HCV-positive individual was positive for HBsAg. Anti-HCV positivity was found in 0.8% (2/236) of the participants who were positive for anti-HBc and in 0.5% (22/4742) of those who were anti-HBc negative, also a difference which was not statistically significant. Thus no association was found between HCV and HBV infections. These findings indicate that in Italy, HCV infection is an uncommon event among young adult males. PMID- 7784806 TI - Prevalence of antibodies against tick-borne encephalitis among residents of north eastern Poland. AB - In 37 out of 613 (6%) residents of north eastern Poland, IgG antibodies to tick borne encephalitis virus (TBEV) were detected at levels exceeding the diagnostic value of 60 VIEU/ml. The prevalence of the antibodies was not related to sex or place or residence. However, significantly higher antibody levels were found in the group of forest workers than in individuals not professionally connected with forestry. PMID- 7784807 TI - Arcanobacterium haemolyticum and streptococcal pharyngitis in army conscripts. AB - Arcanobacterium haemolyticum was found in 1.4% and beta-haemolytic streptococci in 23% of throat cultures from army conscripts with sore throat (n = 498). 38% of the beta-haemolytic streptococci were of group A. Patients culture-positive for A. haemolyticum or beta-haemolytic streptococci had pharyngeal exudate, cervical lymphadenopathy and ear ache significantly more often--but cough less often--than culture-negative patients. The pharyngeal colonization rate of healthy conscripts (n = 232) by A. haemolyticum was 0.4% and by beta-haemolytic streptococci, 6.5%. PMID- 7784809 TI - Human nocardiosis in northern Italy from 1982 to 1992. Northern Italy Collaborative Group on Nocardiosis. AB - We conducted a retrospective survey of nocardiosis in 9 city hospitals in northern Italy from 1982 to 1992. The medical records of 30 patients with documented nocardiosis were reviewed. Microbiological data included morphology, biochemical characteristics, serology and in vitro susceptibility testing. The 29 isolates (1 case was diagnosed on the basis of serological results) were Nocardia asteroides (n = 25) and Nocardia farcinica (n = 4). Predisposing factors including immunosuppression for organ transplant rejection prophylaxis, lung disease (silicotuberculosis and pulmonary fibrosis), solid tumours and hematological malignancies, and AIDS. Three patients had no identified risk factors. 20 cases of pulmonary nocardiosis were observed. Sites of infection in patients without previous pulmonary involvement were: brain abscesses, soft tissues, pericardium, blood, and cerebrospinal fluid. Most strains tested were susceptible to amikacin and imipenem. Resistance to several antimicrobial agents was found, particularly erythromycin, fosfomycin, pefloxacin, sulphonamides and trimethoprim. Antimicrobial chemotherapy included sulphonamides, amikacin, ceftriaxone, imipenem and minocycline. 21 patients survived, although 2 relapsed transiently. Nocardiosis appears to be more common than generally realised by physicians in northern Italy. The local species distribution and disease spectrum are similar to those described elsewhere. Nocardiosis should be part of the differential diagnosis in patients with pulmonary infiltrates or brain abscess, particularly those with predisposing factors. PMID- 7784808 TI - Mortality rate and magnitude of Staphylococcus aureus bacteremia as assessed by a semiquantitative blood culture system. AB - A 4-year retrospective study ascertained the relation between the magnitude of Staphylococcus aureus bacteremia and mortality. 253 episodes of S. aureus bacteremia diagnosed in a Danish regional Department of Clinical Microbiology were included. Blood cultures were routinely done by inoculation of aseptically drawn blood into multiple tubes of bacteriological media. The rate of positive tubes was assumed to distinguish high- from low-grade bacteremia without providing an absolute count of colony forming units. The median number of tubes inoculated was 18 (range 6-48) with approximately 0.5-1 ml of blood per tube. The rate of positive tubes was related neither to the source of infection, i.e. whether the S. aureus infection was nosocomially or community-acquired, nor to the portal of entry. However, mortality increased with increasing rate: it was 18% for rates < 0.30, 23% for 0.30-0.69, 30% for 0.70-0.99, and 37% for a rate of 1.0. Thus, for S. aureus infections the magnitude of bacteremia seems to be a prognostic factor with possible bearings on clinical and therapeutic decisions. PMID- 7784810 TI - Treatment of louse-borne relapsing fever with low dose penicillin or tetracycline: a clinical trial. AB - A clinical trial was conducted in order to evaluate the efficacy of procaine penicillin and tetracycline, respectively, in the treatment of louse-borne relapsing fever. 184 patients (160 men, 24 women) admitted to the Gondar hospital during the rainy season 1992 were assigned to 1 of 4 treatment groups: procaine penicillin 100,000 (PP100), 200,000 (PP200) or 400,000 (PP400) international units (IU) intramuscularly (i.m.), or tetracycline 250 mg per os (TTC, p.o.). All drugs were given as single doses. The overall case fatality rate was 3.3%. Frequency of relapses, Jarisch-Herxheimer-like reactions (JHR) and deaths were significantly different between patients treated with TTC and those treated with PP100. Relapses occurred most often in the group receiving the lowest dose of penicillin (46%), and decreased with increasing dosage of penicillin; none of the patients treated with TTC had a relapse. Occurrence of JHR showed the opposite pattern: whilst 2 (5%) patients treated with PP100 developed a JHR, 16 (29%) in the PP200 group, 10 (31%) in the PP400 group, and 27 (47%) in the TTC group developed a JHR. As mortality is linked to severe JHR, and most relapses are clinically mild and easily treated, these results speak in favour of using low dose penicillin to initiate the treatment of relapsing fever. PMID- 7784811 TI - Prevention of hepatitis B by immunization of the newborn infant--a long-term follow-up study in Stockholm, Sweden. AB - In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used. PMID- 7784812 TI - Endotoxin, interleukin-6 and phospholipase-A2 as markers of sepsis in patients with hematological malignancies. AB - The concentrations of endotoxin, interleukin-6 (IL-6) and group II phospholipase A2 (PLA2-II) were measured in serum or plasma during cytotoxic chemotherapy, fever of unknown origin and sepsis in 56 patients with hematological malignancies and during sepsis and viral infections in 22 non-hematological patients. High concentrations of IL-6, PLA2-II and endotoxin were detected in sepsis, the levels being similarly elevated in hematological and non-hematological patients. The levels of IL-6 and PLA2-II correlated closely with that of C-reactive protein (CRP). The levels of PLA2-II and IL-6 declined earlier than the level of CRP during the course of antimicrobial treatment. The levels of IL-6 also rose earlier than the level of CRP. The ability of IL-6 and PLA2-II and endotoxin to discriminate between sepsis and other causes of fever was comparable to that of CRP. IL-6 and PLA2-II are, together with CRP, valuable tools for the detection of sepsis in patients with hematological malignancies who undergo cytotoxic medication. Endotoxin is not suitable for routine laboratory diagnosis of sepsis. PMID- 7784813 TI - Disk diffusion susceptibility tests: need for laboratory-specific breakpoints. AB - Significant changes were observed in the measured resistance levels of Escherichia coli and Staphylococcus aureus when the Biodisk disk susceptibility test method used in 1992 was replaced with another commercial method, Oxoid. For example, when non-species-specific breakpoints were used, the frequency of cephalotin-resistant E. coli was 12% of all isolates in 1992 but only 4% in 1993; the corresponding figures for the intermediately resistant isolates were 84% and 8%. The population distribution histograms were however, practically unchanged. Thus, the resistance percentages apparently did not reflect the real development of resistance. Similar findings were also made for several other antimicrobials. Susceptibility test breakpoints should therefore be examined separately for all bacterial species in each laboratory, and the application of adjusted laboratory specific breakpoints should be considered. For this purpose, the WHONET computer program provides excellent assistance. PMID- 7784814 TI - Detecting erythromycin resistance in Streptococcus pyogenes: reliability of the disk diffusion method and the breakpoint susceptibility testing method. Finnish Study Group for Antimicrobial Resistance (FIRE). AB - Erythromycin susceptibility of clinical Streptococcus pyogenes isolates was determined at 19 Finnish clinical microbiology laboratories by their routine disk diffusion method and by a screening method adapted from the breakpoint susceptibility testing method. Results obtained at 12 laboratories using 4 major variants of the disk method were further evaluated. From these laboratories, 286 consecutive resistant and 349 consecutive susceptible isolates were sent to the Antimicrobial Research Laboratory, Turku where the MIC of erythromycin was determined. 96% and 97% of the disk results were correct, as compared with MIC results, when general and laboratory-specific breakpoints, respectively, were used. The results of the screening method were comparable to those of the disk method. PMID- 7784815 TI - Antimicrobial resistance in Haemophilus influenzae isolated from blood, cerebrospinal fluid, middle ear fluid and throat samples of children. A nationwide study in Finland in 1988-1990. AB - A nation-wide survey of the prevalence of antimicrobial resistance in Haemophilus influenzae was conducted on isolates collected in 1988-90 from middle ear fluid (MEF), blood, or cerebrospinal fluid (CSF) in infected children or throat samples of healthy children. Altogether 885 strains were examined regarding capsular type b, beta-lactamase production and the minimal inhibitory concentration (MIC) of ampicillin, cefaclor, erythromycin, tetracycline, chloramphenicol, trimethoprim and trimethoprim-sulfamethoxazole for these strains was determined by the agar dilution method. 99% (578/585) of MEF isolates, 93% (112/121) of throat isolates, but only 6% (10/179) of blood/CSF isolates were not of type b (Hib). The rate of beta-lactamase production was 11.4% among Hib strains, 8.0% among non-type b MEF isolates, and 4.5% among non-type b throat isolates. No increase in the prevalence of beta-lactamase production in H. influenzae has taken place in Finland since the early 1980s. Resistance to ampicillin among strains that lacked beta-lactamase activity was rare (0.2%). Of the non-type b MEF and throat isolates, 5.9% and 2.7%, respectively, were resistant to trimethoprim and 3.6% and 2.7%, respectively, to trimethoprim-sulfamethoxazole. Resistance to other drugs was rare (< 2%) in all isolate groups. PMID- 7784816 TI - Invasive Haemophilus influenzae disease: epidemiology and clinical spectrum before large-scale H. influenzae type b vaccination. AB - In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (case/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found. PMID- 7784817 TI - Prevalence of Cryptosporidium sp. in patients with neoplasia and diarrhea. AB - The prevalence of Cryptosporidium sp. was investigated in fecal specimens from 106 patients with neoplasia and diarrhea (74 females, 32 males) by using Ziehl Neelsen and Giemsa stains. Oocystic forms of Cryptosporidium sp. were found in 18 (17%) of these patients. No oocystic form of Cryptosporidium sp. was detected in the control group of 60 patients with neoplasia (37 females, 23 males) but without diarrhea. The frequent findings of Cryptosporidium sp. in patients with neoplasia and diarrhea who are undergoing chemotherapy indicates that a search for this organism is justified. PMID- 7784819 TI - Cranial nerve palsies and cerebral infarction in a young infant with meningococcal meningitis. AB - A previously healthy 30-day-old male infant became ill with fever, poor activity, and refusal to feed for 2 days. A cerebrospinal fluid examination revealed 7.15 x 10(8) leukocytes/l with 72% neutrophils, protein 4.6g/l, and glucose 7 mg/dl. Neisseria meningitidis was isolated from the blood and cerebrospinal fluid. On the fourth day of hospitalization, the baby was found to have left oculomotor and facial palsies, which resolved gradually. He was treated with intravenous penicillin for 2 weeks. A repeat CSF examination revealed a high persisting protein level of 2.9 g/l and a computerized tomographic brain scan revealed a cerebral infarction in the bilateral frontal lobes. The treatment was extended to 4 weeks. No relapse of the infection was noted. This is the first case report of an infant with meningococcal meningitis complicated by cranial nerve palsies and cerebral infarction. This and previous reports, show that meningococcal meningitis at an extremely young age is associated with a greater risk of developing neurological complications. PMID- 7784818 TI - Disseminated toxoplasmosis in AIDS patients--report of 16 cases. AB - Between June 1986 and October 1992, disseminated toxoplasmosis was diagnosed in 16 AIDS patients. 13 cases were diagnosed at autopsy where multiple organ involvement was documented in all 13. Three patients were diagnosed intra vitam. All 3 survived with appropriate treatment. Clinical features indicative of disseminated toxoplasmosis were: fever of unknown origin between 39 degrees and 40 degrees C in 16 cases, clinical signs suggestive of sepsis or septic shock in 15, with progression to multiorgan failure in 10, disseminated intravascular coagulopathy in 6, confusion, disorientation or apathy in 13 and lack of a systemic pneumocystis carinii prophylaxis in all 16. Typical laboratory markers were: CD4 cell counts below 100 x 10(6)/l in 16 cases, elevation of serum lactic dehydrogenase in 16 and creatine phosphokinase (in 4/6), normal or only slightly elevated C-reactive protein (in 9/11), positive Toxoplasma gondii IgG antibodies in 15/16 and negative IgM antibodies in all 16. Lesions indicative of cerebral toxoplasmosis were visualized on cranial computerized tomography in only 3/10 evaluated patients. In patients with advanced HIV infection presenting with a systemic illness, including the clinical and laboratory features described above, systemic Toxoplasma gondii infection must be included in the differential diagnosis. In these patients, specific and if warranted, invasive diagnostic procedures followed by early vigorous therapeutic intervention should be considered. PMID- 7784820 TI - Acute epiglottitis in the adult caused by Neisseria meningitidis. AB - Acute epiglottitis is being increasingly encountered in the adult population. While it has many similarities to its pediatric counterpart, the presentation and associated pathogens are distinct. In addition, although the recent literature has suggested that acute epiglottitis in the adult follows a benign course this is not always the case. Here we describe a case of acute, fulminant epiglottitis in an immunocompetent host, caused by Neisseria meningitidis. PMID- 7784821 TI - Bacteraemia caused by Rahnella aquatilis: report of two cases and review. AB - Rahnella aquatilis, a rare Gram-negative rod, usually found in fresh water, was isolated from blood of a diabetic patient and a patient with laryngeal carcinoma. Both recovered from the infection after treatment with parenteral antibiotics including gentamicin. PMID- 7784822 TI - First documented case of bacteremia with Vibrio vulnificus in Sweden. AB - A few days after a mild trauma to a toe, a 90-year-old woman presented with fever, malaise and cellulitis. On suspicion of erysipelas the patient was initially treated with benzylpenicillin and cefuroxime. Her general condition improved rapidly, but there was local progression with numerous necrotic areas with surrounding bullae. Vibrio vulnificus was isolated from the blood. After susceptibility testing, the patient was finally treated with ciprofloxacin and pivampicillin, and recovered slowly. To our knowledge, this is the first reported case of bacteremia with V. vulnificus in Sweden. PMID- 7784823 TI - Fusobacterium nucleatum, a new invasive pathogen in neutropenic patients? AB - Three chemotherapy-induced neutropenic hematologic patients with severe systemic infection caused by Fusobacterium nucleatum, a Gram-negative anaerobic rod, are described. Anaerobic infections are not very common in this patient category, but in a short period of time, several such patients were seen. The infection was considered to be caused by a combination of chemotherapy-induced mucositis, which served as a portal of entry for the systemic infection, and the antibiotic regime used in these patients. This is a serious infection with a high mortality. In hematological neutropenic patients suffering from severe mucositis and fever, antibiotic therapy should cover anaerobic bacteria. PMID- 7784824 TI - Catheter-related infections by Hansenula anomala in children. AB - During August and September, 1992, we experienced 4 cases of Hansenula anomala (H. anomala, synonym Pichia anomala) fungemia in immunocompromised patients. Two patients had been suffering from a malignant disease, 3 of them had received broad-spectrum antibiotics and a central venous catheter (CVC) had been inserted in all of them. H. anomala was isolated as the sole pathogen from all 4 patients. Three of them responded favorably to fluconazole after withdrawal of the catheter, but one failed. H. anomala should be considered as a possible cause of catheter-related infections. PMID- 7784825 TI - Histoplasma capsulatum infection in three AIDS patients living in Africa. AB - Three AIDS patients are reported, 2 European and 1 African. All 3 developed Histoplasma capsulatum infection while living in Africa. Two developed a pulmonary infiltrate, and 2 had skin lesions. One patient was successfully treated with itraconazole, 400 mg daily; in a second patient, itraconazole was partially successful; the third patient was lost to follow-up before adequate treatment could be started. Histoplasma infection is probably an often undiagnosed complication in African AIDS patients. PMID- 7784826 TI - Etiology of acute sporadic hepatitis in adults in Senegal and Tunisia. AB - Markers for acute hepatitis A, B, C and E virus infections were examined in the sera of 72 patients suffering from acute hepatitis in Senegal and Tunisia. Hepatitis B was responsible for 36% and hepatitis C for 21% of the cases. Acute hepatitis A was not diagnosed. HEV infection was not observed in Senegal and represents only 4% of the acute hepatitis cases in Tunisia. PMID- 7784828 TI - Moraxella catarrhalis bacteraemia in an immunocompetent adult. PMID- 7784827 TI - Hypersensitivity hepatitis due to pyrazinamide. AB - Pyrazinamide hepatotoxicity is considered secondary to a direct and dose-related toxic effect. At currently used doses, pyrazinamide provides effective short-term treatment and is free from serious side effects. We report a case of pyrazinamide induced hepatitis for which the rechallenge data strongly suggest a hypersensitivity mechanism. PMID- 7784829 TI - Dapsone as prophylaxis for disseminated Mycobacterium avium complex infection. PMID- 7784830 TI - Back to work: neck-and-shoulder problems; etiology, prevention, consequences and rehabilitation. Proceedings of an international conference. Stockholm, April 21 23, 1992. PMID- 7784831 TI - Health economy: evaluating the costs and benefits of occupational health programs. PMID- 7784832 TI - Neck-and-shoulder pain, an increasing problem. Strategies for using insurance material to follow trends. PMID- 7784834 TI - Ethical issues in prevention and rehabilitation. PMID- 7784833 TI - The Swedish social insurance system: overview of organization and costs. PMID- 7784835 TI - Conclusions and consensus statements presented by the chairmen responsible for the workshops. PMID- 7784836 TI - Pain physiology and principles of treatment. PMID- 7784837 TI - Clinical aspects of neck-and-shoulder pain. PMID- 7784838 TI - Impairments, disabilities, and handicaps of patients with neck-and-shoulder pain; how are these consequences of disease classified? AB - This article describes various ways of classifying clinical problems related to pain in the neck-and-shoulder regions: the classification of impairments, disabilities, and handicaps, the classification of diseases and injuries, and the classification of chronic pain. It has been argued that diagnosis and classification is bad for patients: "it only labels the patient", it has been said. Of course, the individual patient must be taken care of with a comprehensive view, yet the best way to improve our possibilities to help patients is to strive for better understanding of the mechanisms underlying the problem they present, and this cannot be done without tools of categories. Hence the classifications of clinical problems are absolutely necessary. Classifications do not harm the patients, but lack of knowledge can do so! PMID- 7784839 TI - Principles for medical rehabilitation of patients with chronic neck-and-shoulder pain. PMID- 7784840 TI - An overview of psychosocial and behavioral factors in neck-and-shoulder pain. AB - Psychological factors are suspected to be pertinent in the etiology, maintenance, treatment and prevention of neck and shoulder pain problems. I present a broad overview of current knowledge and trends concerning cognitive-behavioral factors for these pain problems. Although there is a dire lack of research concerning cognitive-behavioral approaches and no psychological theory specific to neck and shoulder problems is currently available, a good deal is nevertheless known about musculoskeletal pain in general. Consequently, there is reason to believe that these factors may be involved in the etiology of neck-and-shoulder disorders. In particular, psychological factors appear to be important in the development and maintenance of subacute and chronic problems. Treatment techniques, adherence, and prevention are examined from a psychological perspective. The application of cognitive-behavioral factors to the treatment and prevention of neck and shoulder pain should provide new avenues which enhance results. It is concluded that while a lack of research precludes definite conclusions, there is ample reason to believe that research into psychological factors may well result in a better understanding of neck and shoulder pain and enhanced treatment and prevention outcomes. PMID- 7784841 TI - Should physical therapists treat pain or dysfunction? What is the primary treatment goal? PMID- 7784842 TI - The new role of Swedish Occupational Health Care in relation to rehabilitation. PMID- 7784843 TI - A new role of the Swedish social insurance office in rehabilitation: current research and development at the Stockholm Office. PMID- 7784845 TI - Predicting injury and identifying the cause. Can we always do so? PMID- 7784846 TI - Scandinavian journal of social medicine: continuation and change. PMID- 7784844 TI - Principles of prevention of neck-and-shoulder pain. PMID- 7784847 TI - Social network, social support and the prevalence of neck and low back pain after retirement. A population study of men born in 1914 in Malmo, Sweden. AB - In this study we investigated the importance of social network and social support systems outside the workplace and workload and psychological job strain in former work for the prevalence of daily neck and low back pain. The study population (n = 621) comprised a random half of all male residents in Malmo, Sweden, born in 1914, of whom 500 (80.5%) participated. Two of the social network and social support indices (social anchorage and availability of material and informational support) were independent of life-style factors (leisure time physical activity, smoking and alcohol consumption) related to daily neck and back pain after retirement (OR = 2.0, 95% CI 1.2-3.4 and OR = 1.7, 95% CI 1.0-2.7, respectively), while the psycho-social and physical factors in former work were not. As no conclusion about the direction of the association can be drawn, prospective studies are needed to further explore these findings. PMID- 7784848 TI - Social inequality in height. A comparison between 10-year-old Helsinki and Stockholm children. AB - The height of children may be used to indicate social inequality. The aim of this study was to analyze the difference in height of the socially more and less privileged 10-year-old Helsinki children in 1963 and 1991 and to compare the social gap to the corresponding gap in 1943, 1963 and 1991 in previous studies of Stockholm children. The difference in mean height of the Helsinki boys in 1963 was 4.5 cm (p < 0.001) and for girls 4.4 cm (p < 0.001). In Stockholm the corresponding differences in 1963 were negligible. Twenty years earlier (in 1943) it was 3.2 cm (p < 0.001) in Stockholm. In 1991 the difference was 1.4 cm (p < 0.05) for boys and 0.6 cm (n.s.) for girls in Helsinki, equivalent to the findings of the Stockholm children at the same time. The well-off Helsinki children already in 1963 were as tall as the Stockholm children. Thus, the decrease of the social gap in height from 1963 to 1991 in Helsinki seems to be mainly due to an increase in height of the socially less privileged children, exactly what was previously found for the Stockholm children between 1943 and 1963. Would the time for the equalization of height mirror the time for the development of the welfare states in Finland and Sweden respectively? PMID- 7784849 TI - Height and social mobility. A study of the height of 10 year olds in relation to socio-economic background and type of formal schooling. AB - Based on a representative sample of Stockholm school-children born in 1943, the association between the height at 10 years of age and the selection to higher and lower education at the same age was examined for upper and lower social groups defined by the father's occupational status. The hypothesis that there is a link between height and change of social position even among children was examined. Upwardly mobile boys (lower class boys selected for higher education) were taller than those staying in their social position. Downwardly mobile boys (higher class boys selected only for elementary education) were smaller than those remaining in their social position. The same tendency was found for girls--although not statistically significant. PMID- 7784850 TI - Social class and cardiovascular disease--an update. AB - Cardiovascular disease is associated with a low social class position in numerous epidemiological studies. The mechanisms behind this finding are not fully known, although several factors may be of importance (e.g. lifestyle, neuroendocrine regulation, foetal deprivation). A better understanding of the biological basis for class-related disease may facilitate efforts in preventive medicine related to cardiovascular health. PMID- 7784851 TI - Smoking or quitting during pregnancy: associations with background and future social factors. AB - Current and future social factors associated with smoking habits during pregnancy were assessed. Data on maternal smoking, social background and the family's development during the 21 years after delivery were gathered for a prospective longitudinal cohort study of 12,068 pregnant women and their children in Northern Finland in 1966 and for a second birth cohort of 9,362 mothers in 1985-86. The prevalence of smoking before pregnancy was 22% in the 1966 cohort (29% in 1985 86). 12% (18%) of the women continued smoking throughout their pregnancy. The following background factors were mainly associated with the mother's smoking and/or continuing during pregnancy in both cohorts when mother's age, parity, place of residence and social class were standardized: mother's age under 23, parity two or more, low social class, urban dwelling, unmarried, gainful employment and heavy smoking. The follow-up responses after 14 and 21 years, respectively, were mostly more favourable among the non-smoking mothers and those who quit smoking during pregnancy-e.g. stable family structure, child's smoking and drinking habits and application for intermediate education. Smoking throughout pregnancy or quitting of smoking late in pregnancy were associated with undesirable future development of the child and family in most of these aspects. PMID- 7784852 TI - Health promotion in schools: policies and practices in Stockholm county, 1990. AB - A survey was undertaken of the policies and practices concerning organisation and implementation of health education and health promotion in schools in 151 of the total 213 Local Educational Areas (LEAs) in Stockholm county in 1990. Health education was included in the workplan of 49% of the responding LEAs, while 39% of respondents had a local action programme or guidelines for health education. Topic areas taught to all pupils and considered most important included alcohol, drug abuse, smoking, sex education, bullying, nutrition and physical exercise. Most senior level schools (55-83%) had written policies concerning pupils using alcohol, drugs or smoking in school, and 68% of LEAs had restrictions on staff smoking in school. Continuing health education was desired by 87% of the respondents. A written programme/plan regarding health education was identified as an important indicator of interest and commitment in health education and health policy issues by the local school. PMID- 7784853 TI - Physicians' experience with Norplant implantable contraceptives in Finland. AB - Norplant contraceptives are manufactured in Finland, but the majority of Norplant users live in the Third World. The objective of this study was to study Finnish family planning physicians experience with and attitudes towards Norplant contraceptives. Three data sources were used: (1) review of articles published in non-commercial Finnish medical journals between 1980 and 1990, (2) a sample of eleven physicians known to have experience with Norplant and chosen by a snow ball method, and (3) a random sample of 22 physicians in charge of public family planning services stratified by municipality and degree of urbanization. The articles reflected a positive attitude towards Norplant, but the authors did not believe that Norplant should replace any previous method of contraception. In the random sample the amount of experience with Norplant was low. In both groups the general attitude towards Norplant was reserved. It was not used as a method of first choice, but was considered a good method for carefully selected women. Norplant was considered troublesome for the physician, requiring surgical procedures, producing side-effects and demanding time for counselling. Adequate use of Norplant calls for a good health care infrastructure, hygienic facilities and trained personnel. These are often lacking in Third World settings. PMID- 7784855 TI - Asthma and allergic rhinitis among Finnish adolescents in 1977-1991. AB - OBJECTIVES: To study whether asthma and allergic rhinitis had increased from 1977 to 1991 and if so, in which subpopulations; to study if structural changes of the society or change in the genetic susceptibility of the population could explain the increase. DESIGN: Cross-sectional surveys with mailed questionnaires in 1977, 1979 and 1991, data from 1977 and 1979 combined; national mortality statistics. SETTING: Finland. SUBJECTS: A nationwide sample of 12-, 14-, 16- and 18- year olds. Sample sizes were 4335 and 3059, response rates 88% and 77%. Mortality statistics from 1958 to 1990. MAIN OUTCOME MEASURES: Point prevalence rate (%) of self-reported, physician-diagnosed asthma and allergic rhinitis, susceptibility of the population measured by probability of respiratory death. RESULTS: Prevalence of asthma was 1.0% in 1977-1979 and 2.8% in 1991, that of allergic rhinitis 5.0% and 14.9%. Logistic regression analysis showed that the increase did not differ in socio-demographic subgroups or parents' smoking groups and that changes in the distribution of socio-demographic variables did not explain the difference either. Respiratory deaths in ages 0-4 were fewer in the birth cohorts measured in 1991. CONCLUSIONS: Physician-diagnosed asthma and allergic rhinitis increased three-fold among Finnish adolescents in 1977-1991. Factors which explain the increase affected all subgroups similarly. Such factors could be changes in diagnostic practices and indoor air quality. Increased susceptibility could explain only a small part. It is likely that a major part of this considerable increase is real. PMID- 7784854 TI - Nonresponse bias due to consent procedures in school-based, health-related research. AB - Written, parental consent was solicited from parents of 517 seventh grade students in four junior high schools in Bergen, Norway for their children's participation in a longitudinal nutrition education study. After having received several reminders, 97.3% of the parents gave their written consent. Students whose parents gave an immediate written consent reported more positive eating habits and were more likely to plan for college than were students whose parents responded after receiving one or more reminders. The observed differences did not severely bias our baseline estimates of these variables, and the magnitude of the observed intervention impact did not change as a result of excluding students whose parents were slow to respond. Excluding these students did, however, affect our ability to identify important factors associated with healthy eating behavior including socio-economic status. Subject selection bias may represent a threat to the validity of studies using a written parental consent procedure. PMID- 7784857 TI - Data quality after restructuring a national medical registry. AB - The validity of the 1991 Finnish Medical Birth Registry data was assessed, with special emphasis on the effects of changes made to the data collection form in 1990. Data abstracted from medical records for all births occurring in 49 hospitals during a five-day sample period (n = 865) were compared to the register information. Good or satisfactory validity was found for 32 of 33 variables, when minor error was tolerated in variables with continuous scales. For diagnoses and procedures, recorded in check-box format, satisfactory validity was found for 10 of 45 variables. Validity could not be assessed for 18 variables because of insufficient number of cases (13 items) or definition problems (5 items). When the results were compared to a 1987 data quality study, many of the variables that had been changed to the check-box format showed improvement in validity. In addition, in some cases a small change in question alternatives or instructions caused a noticeable change in validity. PMID- 7784856 TI - Validity assessment of a social support index. AB - The purpose of this study was to reevaluate the psychometric properties of the social support sumindex used earlier in a Swedish longitudinal study. The results based on the data of a cross-sectional survey in 1992. A randomly selected cohort consisted of 212 men, aged 50 to 60 years. The population sample (n = 4853) was resident in Kuopio Province, Eastern Finland. The 34-item-index was stable. Item total and item-item coefficients showed low internal consistency of the overall index and of most of the subindices. The index had good content validity. Limited evidence of construct validity was noticed. Index assessed well person's social network and support level, and association between the blood pressure and some of the subindices was noticed. The eight underlying subindices did not emerge in factor analysis. Before further using this index we propose its shortening with six items and re-grouping items into subindices. PMID- 7784858 TI - Major differences in cardiovascular risk indicators by educational status. Results from a population based screening program. AB - All people aged 30-59 years living in one primary health care center's catchment area were invited to participate in a population based screening program. A total of 2642 people (68%) participated. An overall risk index for having a heart attack within 5 years (Ps) was calculated based on diastolic BP, smoking status, total cholesterol, and age. Other risk indicators registered were Body Mass Index, and physical activity. A highly significant association between education level and age-adjusted overall risk index for both men (p = 0.001) and women (p < 0.001) was found. Also Body Mass Index, total cholesterol, smoking status, and, for women, diastolic blood pressure showed similar significant variation with education level with higher education associated to lower risk. These findings imply the possibility of a great variation in the "risk" of receiving pharmacological treatment for one's CVD risk factors. PMID- 7784859 TI - Reducing random measurement error in assessing postural load on the back in epidemiologic surveys. AB - OBJECTIVES: The goal of this study was to design strategies to assess postural load on the back in occupational epidemiology by taking into account the reliability of measurement methods and the variability of exposure among the workers under study. METHODS: Intermethod reliability studies were evaluated to estimate the systematic bias (accuracy) and random measurement error (precision) of various methods to assess postural load on the back. Intramethod reliability studies were reviewed to estimate random variability of back load over time. RESULTS: Intermethod surveys have shown that questionnaires have a moderate reliability for gross activities such as sitting, whereas duration of trunk flexion and rotation should be assessed by observation methods or inclinometers. Intramethod surveys indicate that exposure variability can markedly affect the reliability of estimates of back load if the estimates are based upon a single measurement over a certain time period. Equations have been presented to evaluate various study designs according to the reliability of the measurement method, the optimum allocation of the number of repeated measurements per subject, and the number of subjects in the study. CONCLUSION: Prior to a large epidemiologic study, an exposure-oriented survey should be conducted to evaluate the performance of measurement instruments and to estimate sources of variability for back load. The strategy for assessing back load can be optimized by balancing the number of workers under study and the number of repeated measurements per worker. PMID- 7784860 TI - Mortality among Icelandic nurses. AB - OBJECTIVE: The goal of the study was to investigate the mortality pattern of female nurses in a retrospective cohort study with special focus on suicide. METHODS: The mortality of nurses was compared with that of the general female population. The main outcome measure was the standardized mortality ratio (SMR). The participants were 2159 female nurses (ie, all registered nurses in Iceland between 1920-1979). RESULTS: A long-lasting healthy worker effect was found in the cohort. A moderate excess of suicide was observed. A deficit was found for stomach cancer, ischemic heart disease, and respiratory disease. When the cohort was divided according to employment time, there was an excess of brain cancer among those with an employment time of less than 20 years, and all the suicides occurred in that group. The deficit of ischemic heart disease and respiratory disease was more pronounced in the group employed more than 20 years. CONCLUSIONS: It was concluded that nurses, primarily those with a long employment time, enjoy the benefits of their initial good health, but the moderate excess of suicide could be associated with stress and frustration, which the nurses relate to their work situation. PMID- 7784861 TI - Occupational back pain--an unhelpful polemic. AB - In most industrialized countries, disability and work absence due to occupational back pain have risen steadily in recent decades. Conventional views of the causes of this slow epidemic tend to fall into one of the following three areas: (i) the clinical pathology view, which attributes the level of pain and disability to either the severity of the initial injury or to psychosomatic conditions; (ii) the biomechanical exposures view, which attributes the problem to hazardous and preventable conditions of work; and (iii) the perverse incentives view, which suggests that reporting and disability are influenced by a combination of work dissatisfaction and accessible disability benefits. This paper reviews, from an epidemiologic perspective, the specific methodological hurdles faced during investigations of the etiology of occupational back pain. It is argued that methodological issues have contributed to the perpetuation of the three distinct but incomplete views of the problem. New research directions are suggested and a broader interdisciplinary perspective is proposed to help resolve the existing polemic. PMID- 7784862 TI - Dermatoses determined in a population of farmers in a questionnaire-based clinical study including methodology validation. AB - OBJECTIVES: The study analyzed skin diseases in a population sample of Finnish farmers descriptively and in the process validated the question "Do you have a skin disease now?" METHODS: All farmers from one Finnish municipality were surveyed for dermatoses, first with a questionnaire and then with a clinical examination of those who reported dermatoses. Another population of farmers answered a set of questions immediately before a clinical examination, and the self-report of current dermatosis was validated. RESULTS: Eczema was diagnosed for 66% of the women and 53% of the men who had reported dermatosis in the questionnaire study 6 to 12 months earlier. Toe-web maceration, psoriasis, folliculitis, and acne were, after eczema, the most frequent diagnoses (in that order). In more than 50% of the cases, the location of clinically determined dermatoses corresponded with the skin disease areas reported 6 to 12 months earlier. In the validation study, everyone who reported a skin disease immediately before the clinical examination were found to have a skin disease. In addition 22% of those not reporting dermatosis were found to have a skin disease. Toe-web maceration was the most common dermatosis not reported by the farmers. CONCLUSIONS: Finnish farmers suffered from the same type of dermatoses as other populations. The prevalence of eczema and hand eczema was similar to that of other risk populations. A self-report of current dermatosis is probably a good indicator of the point prevalence of explicit skin diseases in populations. PMID- 7784863 TI - Single-strand breaks in deoxyribonucleic acid in fire fighters accidentally exposed to o-nitroanisole and other chemicals. AB - OBJECTIVES: The aim of the study was to detect single-strand breaks in deoxyribonucleic acid (DNA) in mononuclear blood cells of fire fighters exposed to o-nitroanisole and other substances released into the environment during an accident in a chemical plant. METHODS: The level of DNA single-strand breaks in mononuclear blood cells was detected by alkaline elution. The results were compared for 16 fire fighters who worked in a contaminated area for about 8 h and two reference groups (one of fire fighters who had not worked in the contaminated area, group I, and one of persons without any apparent occupational exposure to genotoxic substances, group II). RESULTS: The mean normalized elution rate (nER) 19 d after the accident was slightly but statistically significantly (P < 0.05) higher for the exposed fire fighters [mean 1.48 +/- 95% confidence interval (95% CI) 0.21] than for reference group I (mean 1.21 +/- 95% CI 0.21) or reference group II (mean 1.17 +/- 95% CI 0.18). No statistically significant difference was found between reference groups I and II. Another analysis was performed three months after the first. The level of DNA single-strand breaks (mean nER 1.12 +/- 95% CI 0.11) was no longer increased in comparison with the levels of the reference groups. CONCLUSIONS: DNA single-strand breaks were increased in fire fighters exposed to o-nitroanisole and other substances. In comparison with the extent of DNA strand breaks found in other occupational groups the increase was only moderate. The observed decrease in DNA single-strand breaks to the reference level in exposed fire fighters three months later suggests a DNA repair mechanism for DNA single-strand breaks caused by o-nitroanisole. PMID- 7784864 TI - Assessment and grouping of occupational magnetic field exposure in five electric utility companies. AB - OBJECTIVES: Occupational exposure to 60-Hz magnetic fields was surveyed among randomly selected workers in five electric power companies. METHODS: The study facilitated the examination of exposure variability and provided the base for a job-exposure matrix linking health outcomes and occupational magnetic field exposures. RESULTS: Average exposures ranged from 0.11 to 1.50 microT. The differences among the five companies were small, the more urban companies showing somewhat higher averages. The day-to-day component of variance exceeded the within- and between-group components of variance. The final job-exposure matrix consisted of five groups with average exposure levels of 0.12, 0.21, 0.39, 0.62, and 1.27 microT. Given the variance in exposure, even this optimal grouping considerably overlapped. CONCLUSIONS: The job-exposure matrix used in this study efficiently incorporated the differences in exposure within occupational categories between companies and provided an objective and statistically based method for estimating cumulative magnetic field exposure. PMID- 7784865 TI - Health symptoms and the work environment in four nonproblem United States office buildings. AB - OBJECTIVES: The objective of this study was to quantify health symptom reports in four "nonproblem" buildings and to assess the relationship between symptoms and air quality measures, workstation characteristics, and psychosocial aspects of the workplace. METHODS: Environmental sampling was conducted in four office buildings occupied by employees working for the state of Washington in March of 1992. A questionnaire was concurrently administered to building occupants. RESULTS: While measured contaminant levels were low, symptoms were frequent. Fifty-five percent of the 646 respondents reported recent symptoms which affected the eyes, nose, or throat and improved when away from work. Symptoms were not associated with measured contaminant levels, but, rather, with perceptions about air movement, dryness, odors, and noise. Psychosocial factors were less strongly associated with symptoms. CONCLUSIONS: Even in nonproblem buildings, symptom reports can be frequent and may represent overall satisfaction with the work environment. In response to symptoms ascribed to air quality problems, it may be appropriate to address employee perceptions regarding the work environment in addition to evaluating environmental characteristics relating to chemicals, biological contamination, air movement, temperature, and humidity. PMID- 7784866 TI - Musculoskeletal disorders among operators of visual display terminals. AB - Using a visual display terminal (VDT) is today a common occupational task with both benefits and hazards. One of the hazards is the occurrence of musculoskeletal disorders. This paper examines the possible causes of such disorders and suggests some preventive strategies. The debate on the relationship between musculoskeletal disorders and VDT usage usually centers around occupational factors (eg, constrained posture, poor ergonomic design of the workplace, equipment design), work-related psychological factors (eg, perceived high job demands, mundane, boring and repetitive job activity, little control, poor support from colleagues and superiors), and psychosocial factors (eg, biodemographic characteristics such as age, previous musculoskeletal injuries, emotional stress, family burden, environmental factors). Improving the ergonomic design of VDT workstations, changing occupational legislation, and improving occupational health services have been suggested as means to decrease the incidence of musculoskeletal disorders among VDT workers. Much research with a multidisciplinary approach is still needed. PMID- 7784867 TI - Does welding stainless steel cause cancer? PMID- 7784868 TI - Sex ratio of offspring of female physiotherapists exposed to low-level high frequency electromagnetic radiation. PMID- 7784869 TI - [Thrombendarterectomy in aorto-iliac occlusive disease]. AB - An overview is given of the history and operative techniques of open and semiclosed thrombendarterectomy (TEA) for aortoiliac obstructive disease. The second part of the paper reviews the long-term results of 514 aortoiliac TEA's performed in 415 patients between 1959 and 1972. The data were prospectively acquired and the analysis was done on a retrospective basis. Median follow-up was over 15 years. Open and semiclosed TEA were performed on 167 and 347 limbs respectively. Hospital mortality was 1.2% and operative morbidity 11.1%. The overall life-table patency rate at 5, 10, 15, and 20 years was 93.4%, 90.4%, 84.2% and 69.5% respectively. Patency rate depended on significant factors: open versus semiclosed method (p < 0.04), anatomic localization: common iliac artery versus external iliac artery (p < 0.0004), preexisting stage of occlusive disease: stage II versus stage IV (p < 0.008), and gender: female versus male (p < 0.007). Patient's age was not a predictive factor on patency. The limb salvage rate was greater than 90% even in long-term follow-up. We conclude that in aortoiliac obstructive disease both open and semiclosed TEA give highly satisfactory long-term results with low mortality and morbidity rates. PMID- 7784870 TI - [Comparative study of preliminary and definitive anatomo-pathological diagnoses in 375 autopsies in adults]. AB - For the past 5 years the institute of pathology of the University of Lausanne has been delivering both provisional and final autopsy reports. The provisional reports are based mainly upon macroscopic findings, whereas the final reports include the information provided by supplementary investigations such as microscopy, histochemistry, more rarely electron microscopy, immunohistochemistry and/or microbiology. The reliability and usefulness of the provisional reports were analyzed by systematic comparison between the provisional and final reports of 375 adult post-mortems as well as through an inquiry among requesting physicians. No significant difference was found between the two reports in 77.1% of the cases. In 22.1% the supplementary investigations provided information which had a bearing on the final diagnosis and made it possible to complete or correct the macroscopic diagnosis. In 0.8% the significant difference was due to the omission, in the provisional report, of an obvious macroscopic diagnosis. Finally, 95% of the consulted physicians found the provisional reports useful because of the precise written and particularly rapid information they provided. These results not only demonstrated that the establishment of such provisional reports is fully justified, but further emphasize the fundamental and complementary role played by the final autopsy reports. PMID- 7784871 TI - [Torsion of the large omentum in Prader-Willi syndrome]. AB - Although excess fat deposition in the omentum and obesity have been suggested as possible predisposing factors for omental torsion, no previous descriptions of an association between the Prader-Willi syndrome and omental torsion have been found in the literature. We therefore report the case of a 6-year-old boy with Prader Willi syndrome and primary torsion of the greater omentum. PMID- 7784872 TI - [Lung transplantation]. AB - Human lung transplantation was successfully performed in the early eighties and is now an option for patients with endstage lung disease, which is associated with poor survival. Most frequent indications for lung transplantation are emphysema, cystic fibrosis, fibrosing alveolitis, primary pulmonary hypertension and Eisenmenger's syndrome. Single lung transplantation (SLT) is most often performed in emphysema, fibrosing alveolitis and other diseases which are not associated with chronic infection of the lung. Double lung transplantation was recently replaced by the technique of sequential single lung or bilateral lung transplantation (BLT). Cardiopulmonary bypass can often be avoided and problems of the airway anastomosis are less frequent using BLT. Main indications for this procedure are cystic fibrosis, bronchiectasis and primary pulmonary hypertension (PPH). In PPH often only SLT is performed. Cor pulmonale is reversible following SLT or BLT even if the heart is not replaced. Combined heart-lung transplantation (HLT) is reserved for some cases of Eisenmenger's syndrome and few centers still prefer HLT in patients with cystic fibrosis. Patients are usually accepted for transplantation when they are considered to have life expectancy of 12 to 24 months. Quality of life and physical working capacity are severely decreased and patients suffer dyspnea NYHA grade III or IV. Most of the patients are hypoxic and need continuous oxygen therapy. Hypercapnia is also a negative predictive factor for survival without transplantation. In PPH cardiac index of less than 2 litres/m2 is associated with poor outcome. Not only absolute values for FEV1 and pO2 have to be considered in finding the best moment for assessment for transplantation but the clinical course of the disease during previous months and years also has to be taken into account. Contraindications to transplantation include acute infection, concomitant diseases of other organs, bronchial carcinoma and psychiatric disorders if noncompliance is likely. To achieve good results after lung transplantation, proper donor and recipient selection, experienced surgery and careful postoperative management are essential. Complications must be diagnosed early to provide effective treatment. Most complications occur within the first months after surgery. Early complications include primary organ failure, pleural bleeding, problems at the site of the airway anastomosis, infection and acute rejection. Acute rejection is common but can be treated successfully if diagnosed early.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7784874 TI - [And if we speak of continuing education!]. PMID- 7784873 TI - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). On systematic goiter therapy and prevention. 1922]. PMID- 7784875 TI - [The chemical solubility and stability of low-melting dental porcelains]. AB - The aim of this investigation was to study the chemical solubility of 3 new low fusing ceramics (Duceram-LFC, Duceragold and Vita Omega 800) in comparison with a conventional PFM-ceramic (Vita Omega) together with different surface treatments. Additionally, the three-point flexure strengths were measured. Although the test conditions were very stringent in comparison to the standard solubility test, all ceramics comply with ISO/DIS 6872 specifications, and are thus deemed to be well tolerated in the oral environment. Vita Omega demonstrated the lowest chemical solubility. Mechanical polishing of the surfaces of LFC and Duceragold ceramics produced lower solubility results as compared to glazing. Vita Omega and Omega 800 behaved contrarily. After repeated hydrolysis testings Ducera-LFC demonstrated the highest disintegration resistance. The three-point flexure strengths of low-fusing ceramics were generally higher than that of the conventional PFM-ceramic. As opposed to the other ceramic materials tested, the flexure strength of Duceram-LFC increased significantly after hydrolysis testing. PMID- 7784876 TI - [A mathematical model for the treatment of root surfaces with rigid and flexible instruments]. AB - The objective of this study was to assess the accessibility of root surfaces using stiff instruments in order to evaluate the advantages of a new flexible instrument-set for the treatment of periodontally diseased roots. 100 extracted human teeth were sectioned and histologically prepared. They were divided into two groups each containing 50 sections. Group I showing the interproximal, group II the buccal/lingual morphology. Slides were taken of each section under a constant magnification (3.2x) and a selected number of distances and angles were measured on each section. Using trigonometric functions the following parameters were calculated and set in relation with hypothetical probing depths ranging from 0-15 mm: 1.) instrument length; 2.) change of the instrument angulation; 3.) theoretical deflection of the gums. Statistical analysis was performed using Student's t-test. For a given probing depth the instrument length was independent of the sites and the deflection of the gums. When a deflection of the gums was assumed, the instrument angulation was constant; an exponential decrease of the angulation with increasing probing depth was found with gum deflection. The deflection was increasing with increasing probing depth, showing statistically significant differences between interproximal and buccal/lingual sites (p < or = 0.05). In conclusion the instrument length seems not to be an impeding factor for the accessibility of root surfaces in contrast to the instrument angulation and the fact that teeth are encircled by the gum. Due to morphological reasons stiff instruments seem to be inferior to flexible instruments when a non-surgical root treatment is performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784877 TI - [Personnel and instrumental differences in the treatment of root surfaces. A comparison on a phantom model]. AB - The treatment of root surfaces in periodontal lesions with mechanical instruments is becoming more and more popular as an alternative to the conventional treatment with curets. In this in-vitro study a phantom head with a simulated periodontitis was used. The aim of this investigation was to determine the percentage of the subgingival non-treated root surfaces after treatment with different instruments and by different persons. Newly developed mechanical file instruments (Rootshape) were tested. Hand curets served as control group. The treatment of the teeth was carried out by three groups, each including 4 people. Group one were dental hygienists (DH), group two dentists with (Spez) and group three dentist without (Zaz) experience in the therapy of periodontal diseases. They were asked to perform a scaling and root planing on six teeth (16, 21, 24, 36, 41, 44) both with curets and Rootshape files. The size of the non-treated areas was subsequently determined planimetrically and expressed as percentage of the entire subgingival root surface. Independent of the group the percentage after file treatment was significantly lower (mean 9.85 +/- 7.78%) than that after curet treatment (mean 14.74 +/- 10.20%). Significant differences were found when the three groups were compared after treatment either with files or curets (DH 9.61 +/- 8.02%, Spez 12.11 +/- 8.01%, Zaz 15.18 +/- 11.01%; p < 0.001). Zaz working with files achieved as good results as DH or Spez with curets (p < or = 0.05). The results indicate that the files represent an alternative to hand instruments concerning the accessibility of root surfaces. PMID- 7784878 TI - [The intraoral bacterial colonization of temporary denture plastics]. AB - Plastic materials used for temporary crowns and bridges in prosthetic dentistry are investigated with regard to the possibility of their microbial colonization. For this purpose four different kinds of materials, i.e. Resincap, Trim, Snap (Polyalcylmethacrylate) and Protemp (Bisphenol-A-Glycidyl-Methacrylate) were chose. With the help of 10 test persons in vivo experiments were carried out. After a period of two weeks it could be verified, that the bacteria have a stronger affinity to Protemp than to Polyalcylmethacrylate. The hypothesis, that the different intensity of colonization is due to the roughness of certain surfaces could be confirmed by additional experiments. PMID- 7784879 TI - [The TIME technic. Local osteoplasty with micro-titanium mesh (TIME) for alveolar ridge augmentation]. PMID- 7784880 TI - [Deciduous tooth reconstruction with composite polymers. The ITN care of amelogenesis imperfecta (first dentition) with composite polymeric materials as well as steel crowns--a case report]. PMID- 7784881 TI - ["Every movement, even out on the periphery, immediately affects the chief, who is in the middle, and indeed abruptly". Interview by Kurt Venner]. PMID- 7784882 TI - [Modern prosthodontics--with and without implants. A report on the 4th Winter Symposium, Going/Tirol (A), 15-21 January 1995]. PMID- 7784883 TI - [Esthetic dentistry. Interview by Kurt Venner]. PMID- 7784884 TI - [The Swiss Union for Preventive and Restorative Dentistry founded. Interview by Kurt Venner]. PMID- 7784885 TI - [The first case in Switzerland: profession-related HIV infection]. PMID- 7784887 TI - [Transfer without the particulars of concrete questioning is not ideal. Interview by Kurt Venner and Catherine Strahm]. PMID- 7784886 TI - [A response to the letter of Dr. J. Stassen in SMfZ 2/1995]. PMID- 7784888 TI - ["Do not do the maximum but what is truly necessary". The meeting of consulting dentists and specialists in insurance of 26 January 1995 at Bern]. PMID- 7784889 TI - [The founding of the Swiss Association of Working Groups for the Treatment of Cheilognathopalatoschisis and Craniofacial Anomalies]. PMID- 7784890 TI - [Caries prevention in Peru]. PMID- 7784891 TI - [Amino acid neurotransmitter receptors of carp brain expressed in amphibian oocytes]. AB - GABA receptor and inotropic glutamate receptors were expressed in amphibian oocytes and studied with the voltage-clamp technique and pharmacological method after injection of mRNA from carp (Carassius carassius) brains. It was found that about 90% of the response to GABA was mediated by GABAA receptor, but there was also about 10% of the response which was insensitive to bicuculline, a selective antagonist to GABAA receptor, baclofen, a selective agonist to GABAB receptor, had no effect on the injected oocytes. These observations suggest the existence of GABAC receptor. Subtypes of glutamate receptors, including NMDA subtype, KA/AMPA subtype and metabotropic glutamate receptors were also expressed and the dose-response relations were studied. Furthermore, we found that NMDA competitively suppressed the current response to KA, suggesting that NMDA probably was a weak antagonist of the KA/AMPA receptor. PMID- 7784892 TI - [Aging changes of the electro-physiological characteristics of hypothalamic neurons in culture]. AB - The aging changes of the electrophysiological characteristics of the hypothalamic neurons cultured for 0-140 days were studied in neonatal SD rats by the intracellular microelectrode recording technique. The growth velocity of the neurites was used as an index to divide the living process of the neurons into three periods, i.e. recovering period, growth period and aging period. It was found that the time constant and the membrane capacitance reached a top value in the growth period and then decreased significantly in the aging period (P < 0.05, P < 0.01). In the recovering period, the membrane resistance reached the highest; and then decreased significantly in growth period but did not change significantly in the aging period. The amplitude of the membrane resting potential was about -30 - -60 mv and increased with the days in vitro (P < 0.05). The neurons could produce single or burst discharges. It appears that certain electrophysiological characteristics of the hypothalamic neurons in culture could characterize certain aging changes. PMID- 7784893 TI - [Preventive effect of quinacrine on the development of heat injury by stabilizing membrane phospholipids metabolism and beta-adrenoceptor]. AB - Previous studies have demonstrated that the activation of phospholipase A2 (PLA2) during heat stress would caused disorder of membrane phospholipids metabolism, accompanied by a decrease in phosphatidylcholine and phosphatidyl-serine and an increase in arachidonic acid. In heat stressed rats, a down-regulation of beta adrenergic receptor in lung tissue was observed due to activation of PLA2. In the present work, it was demonstrated that pretreatment of rats with PLA2 inhibitor, quinacrine (20 mg/kg, I.P.), 1 h before heat stress could block these membrane lipid alterations, and the tolerance of rats to heat exposure was enhanced. The effect of quinacrine on the thermotolerance of marching soldiers with 15 kg of load under hot environment was also investigated. The results indicated that in the soldiers taken orally 200 mg quinacrine 1 h before marching, their heart rate, body temperature, accumulation of blood lactic acid and the changes of index of heart function were significantly improved as compared to the control group at the end of 3 h marching. According to these data, it can be concluded that quinacrine is a useful drug to prevent derangement of beta-adrenoceptor and membrane phospholipids metabolism in the development of heat stress. So as to prevent heat injury, and to improve tolerance to heat stress. PMID- 7784895 TI - [Reversible elimination of K+ and Na+ currents at motor nerve terminals by SM486, a derivative of artemisinin]. AB - Some derivatives of Artemisinin have been used as malariacides. Artemisinin derivative SM486 is water-soluble and has been shown also to have local anesthesia action. Here we report the effect of SM486 on Na+ and K+ channels at motor nerve terminals. Experiments were performed on mouse triangularis sterni nerve-muscle preparations. Presynaptic currents were picked up with a microelectrode inserted into the subendothelial space of the superficial nerve bundle under visual control using a x400 magnification water immersion objective. The results showed: (1) Both IK and INa were depressed in a dose-dependent manner, although the minimal effective concentration of SM486 for IK was lower than that for INa; (2) The depression was reversible as shown by the fact that the nearly completely blocked INa and IK currents could be restored to the control by simply washing away the perfusate SM486. (3) The decrease of IK was progressive, while the change of INa always began after IK proceeded to decrease rapidly. The effects of procaine on INa and IK are similar to SM486 but the effective concentration was higher. PMID- 7784894 TI - [Effect of hypothalamic paraventricular beta-endorphin on burn shock in rats]. AB - Dynamic changes of immunoreactive beta-endorphin (ir-beta-EP) in perfusates collected from hypothalamic paraventricular nuclei at different times after burn, and the effects of intrahypothalamic paraventricular microinjection of beta endorphin or its antiserum on various cardiac indices (MAP, dP/dtmax, Lvsp and HR) and survival time, were observed in anesthetized SD rats after third degree burn of 20% total body surface area. The results showed a significant increase of ir-beta-endorphin contents in the perfusate with the appearance of two peaks. According to the cardiac indices and mean survival time, the condition of the burned animals were improved by injection of anti-beta-endorphin serum, while injection of beta-endorphin did the reverse. The above results suggest that massive accumulation of beta-endorphin in the paraventricular nucleus appears to be one of the important factors detrimental to burn shock. PMID- 7784897 TI - [Elevated expression of B-50 (GAP-43) -mRNA in a subpopulation of olfactory bulb mitral cells following axotomy]. AB - Using in-situ hybridization method. We studied B-50 (GAP-43) mRNA expression following lesion of olfactory bulb mitral cells in rats. Expression of B-50 mRNA in approximately 40% of the mitral cells was upregulated in response to transection of their axons in the lateral olfactory tract (LOT). Enhanced expressin persisted for 10 days postlesion but than declined to control levels by 4 weeks after the lesion. A large proportion of the mitral cells gradually degenerated subsequent to LOT transection. Thus, a subpopulation of mitral cells maintain their ability to upregulate B-50, a protein characteristic of growing axons, but enhanced B-50 expression is not accompanied by regeneration of the severed LOT. PMID- 7784896 TI - [Fate of human fetal dopamine neurons transplanted into rhesus monkey model of Parkinson's disease: a tyrosine hydroxylase immunocytochemical study]. AB - To predicate the value of human fetal substantia nigra transplantation in clinical treatment of Parkinson's disease (PD), dissociated cells of substantia nigra from 8-12 week old abortive human fetus were grafted into the neostriatum of 5 adult rhesus monkeys with hemiparkinsonism induced by unilateral injection of MPTP. At 2, 5 and 12 months after transplanting the monkeys were sacrificed for tyrosine hydroxylase (TH) immunocytochemistry to examine the survival and possible synaptic contact of transplanted dopamine (DA) neurons. Transplanted TH immunoreactive cells took a pattern of patches scattered in the neostriatum. Each of the cell patches consisted of 3-10 cells. The TH immunoreactive fiber network was seen in the neostriatum. Electron microscopic survey revealed that TH+ buttons arising from grafted DA neurons formed symmetric or asymmetric synapses with TH- dendritic shafts/spines, and TH+ dendrites were seen to form synapses with TH- axons of the host. Additionally, there were a few synapses formed by TH+ axonal terminals with negative buttons. The results suggest that DA neurons from 8-12 week old abortive human fetus are able to survive grafting into the neostriatum of monkey, a species phylogenetically very close to human, and to establish reciprocal synaptic connectivity with the host even at 2 months post transplanting. It is, therefore, inferable that embryonic human DA neurons transplanted into human neostriatum may have the same fate as in monkeys. PMID- 7784898 TI - [Dual mode control of head movements during eye-head coordination]. AB - Eye-head coordination during the shift of gaze is investigated. Dynamic trajectories of eye movements and head movements were measured for exploring the control mechanism of the head movement in eye-head coordination. The experimental results revealed the dual mode control of the head movement in eye-head coordination: a linear control for small amplitude movement (less than 30 degree), and a Bang-Bang control for larger amplitude. PMID- 7784899 TI - [Study of H(+)-Ca2+ exchange in cultured heart cells after hypoxia and reoxygenation]. AB - Reoxygenation is more serious for hypoxic myocardial cells because of the subsequent calcium overload. The calcium overload is known due to augmentation of H(+)-Na+, Na(+)-Ca2+, exchange during pH paradox. But the present experiment showed that, when H(+)-Na+, Na(+)-Ca2+ exchange was inhibited, calcium could still enter myocardial cells after hypoxia or reoxygenation. Similar result was observed after using Na(+)-Free solution, suggesting that calcium entrance into the cell was unrelated to Na+ channel. It was further shown that calcium accumulation was related to pH gradient across the myocardial cell membrane, i.e., being increased with increase of H+ concentration in the cell. Therefore, it appears that, besides H(+)-Na+, Na(+)-Ca2+ exchange, H(+)-Ca2+ exchange is one of the reasons of calcium overload during intracellular pH paradox. PMID- 7784900 TI - [Angiotensin II induces c-fos and c-myc proto-oncogene expression in the left ventricle]. AB - In the present study, the effects of angiotension II on the expression of protooncogene c-fos and c-myc in the left ventricle were investigated on Langedorff heart preparations. It was observed that angiotensin induced both c fos and c-myc expression in a dose-dependent manner and the c-fos expression showed an earlier appearance than c-myc. All these induced expressions were blocked by a Angiotensin II receptor antagonist saralasin. The Angiotensin II induced expression of c-fos was also blocked by TTX, but the c-myc gene expression was unaffected. PMID- 7784901 TI - [Morphine-3-glucuronide (M3G) potentiates noxious stimulus-evoked Fos protein like immunoreactivity in the rat spinal cord]. AB - The effect of morphine-3-glucuronide (M3G) on noxious stimulus-evoked Fos protein like immunoreactivity in the rat spinal cord were assessed by ABC method. It was found that a dose-dependent increase of Fos-like immunoreactive neurons could be induced by M3G intrathecal injection followed by formaline injection into hindpaw. With high dosage M3G (1.1 x 10(-7) mole), dense Fos-like labelling was found in the superficial and the deep dorsal horn bilaterally, While with low dosage M3G (5.4 x 10(-8) and 1.1 x 10(-8) mole), most of the positively labelled neurons were only found in laminae I and II of the ipsilateral dorsal horn to the injured paw. The above results revealed that M3G exerts a potentiating effect on the noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. PMID- 7784902 TI - [Effects of recurrent laryngeal nerve on thyroid hormone secretion in rats]. AB - The effects of recurrent laryngeal never (RLN) on serum thyroid hormones and thyroidal radioiodide uptake were examined in rats. The results are (1) Serum thyroxine (T4) level increased significantly after section of unilateral RLN. When the sectioned peripheral end was stimulated immediately after section, the serum T4 level went even significantly lower than the control within 30 minutes. (2) Radioiodide uptake by homolateral thyroid increased significantly after section of unilateral RLN. These results indicate that RLN normally exerts an inhibitory effect on thyroxine secretion possibly mediated by muscarinic receptors. PMID- 7784903 TI - [Depression of TTX-blocking effect on Na+ current by 8A5, an anti-TTX monoclonal antibody]. AB - Anti-TTX effect of 8A5 on Na+ current was observed by whole-cell voltage-clamp technique in NG108-15 cells. The results show that 8A5 inhibits TTX action efficiently: (1) When 1 mumol/L TTX is added to the normal perfusion solution INa disappears immediately, and can be restored to the control level with futher addition of 8A5. (2) When the cell is pre-incubated with 1 mumol/L 8A5, 1 mumol/L TTX can only cause a partial inhibition of INa. PMID- 7784904 TI - [Effects of stimulating rabbit's cerebral cortex on respiratory frequency and amplitude]. AB - The effects on respiration upon stimulation of different areas of cerebral cortex were studied in 38 urethance anesthetized rabbits after both vagotomy and section of the maxillary division of trigeminal nerves. The results showed that: (1) Light continuous stimulations of the limb motor area (L) enforced inspiration by increasing respiratory frequency (RF) and tidal volume (TV). Stimulation of the facial motor area (F) increased RF notably, but depth of expiration and inspiration were notably decreased. Upon stimulation of the masticatory motor area (M), expiration or inspiration was accentuated, RF and TV were obviously increased. Upon stimulation of the posterior orbital area RF and TV were decreased markably. No obvious effects on respiration were observed on stimulation of the other areas of the cortex. (2) With shortened total period of stimulation, a stimulating L, F or M area would cause a longer period of apnoea after expiration and resumption of inspiration insured an increased TV. PMID- 7784906 TI - Medical genetics in primary health care. PMID- 7784907 TI - Congenital anomalies in black South African liveborn neonates at an urban academic hospital. AB - STUDY OBJECTIVE: The aim was to study the spectrum of clinical problems and outcomes in infants born at an urban academic hospital. In consequence, as part of the overall study, the incidence of congenital anomalies and the outcomes of affected infants were recorded. DESIGN: This was a prospective, hospital-based study, undertaken on liveborn infants born over a 3-year period, 1 May 1986 to 30 April 1989. SETTING: Kalafong Hospital, Pretoria. MAIN RESULTS: A total of 17,351 liveborn infants was examined and the total congenital anomalies incidence was 11.87 per 1,000 livebirths. The central nervous system was the system most frequently involved (2.30 per 1,000 livebirths), followed by the musculoskeletal system (2.13 per 1,000 livebirths). The commonest individual congenital anomaly was Down syndrome (1.33 per 1,000 livebirths), followed by neural tube defects (0.99 per 1,000 livebirths) and ventricular septal defects (0.69 per 1,000 livebirths). In 11% (2.25 per 1,000 livebirths) of neonatal deaths, infant loss was attributable to congenital anomalies. CONCLUSIONS: The incidence of congenital anomalies in black South African neonates, born in an urban setting, is as high as in other First- and Third-World countries, and the incidence of some individual congenital anomalies is higher. This study indicates the need for further research and the establishment of prenatal, genetics and paediatric facilities to manage these problems. PMID- 7784905 TI - [Effect of prolactin on gonadotropin-induced ovarian estrogen and progesterone production in mouse]. AB - Immature mice (21-23 days old) were injected with 8 IU PMSG to stimulate follicle growth and followed 24 h later by either injection of 8 IU hCG alone or hCG plus 100 micrograms of prolactin (PRL). The animals were killed at 3, 12 and 24 h after hCG treatment. The ovaries and blood samples were collected. Granulosa cells were prepared for incubation. Progesterone and estrogen concentrations in both the serum and the culture medium were determined. The results showed that PRL significantly enhanced hCG-induced mouse serum progesterone content, while serum estrogen concentrations were considerably decreased by the co-injection of PRL. Prolactin was also capable of stimulating gonadotropin-induced progesterone secretion in the cultured GC. However, the aromatase activity induced by FSH and hCG was remarkably inhibited by the presence of PRL. These data suggest that PRL inhibition of hCG-induced ovulation may be due to its interference with the gonadotropin-induced estrogen production by the follicular granulosa cells. PMID- 7784908 TI - Congenital anomalies in rural black South African neonates--a silent epidemic? AB - STUDY OBJECTIVE: To ascertain the incidence and spectrum of congenital anomalies in neonates born in a rural hospital. DESIGN: This was a prospective, hospital based study, undertaken on liveborn neonates over the period 12 June 1989 - 31 December 1992. SETTING: Mankweng Hospital, Sovenga, Northern Transvaal. MAIN RESULTS: Of a total of 10,380 neonates born during this period, 7,617 (73.4%) were examined within the first 24 hours of life. On the basis of published observations, only 26.2% of severe congenital anomalies diagnosable by age 5 years are diagnosable at birth. In this South African study the finding at birth of severe, externally visible congenital anomalies in 14.97 per 1,000 livebirths could mean that by age 5 years the minimum cumulative incidence of severe congenital anomalies may involve 57.14 per 1,000 children. Extrapolating from other Third-World studies, the cumulative incidence of severe congenital anomalies in such communities may affect up to 84.85 per 1,000 children by the age of 5 years. High incidences of neural tube defects (3.55 per 1,000 livebirths) and Down syndrome (2.10 per 1,000 livebirths), both conditions which can be prevented by prenatal screening, were recorded. CONCLUSIONS: These figures indicate the necessity for inclusion of appropriate prenatal, genetic, family planning and paediatric facilities into the primary health care delivery system of rural areas, to manage such problems and to initiate programmes to reduce the incidence of selected congenital anomalies such as Down syndrome and neural tube defects. PMID- 7784909 TI - The costs and benefits of a vaccination programme for Haemophilus influenzae type B disease. AB - Haemophilus influenzae type b (Hib) infection is a major cause of severe bacterial infection in young children in South Africa and world-wide. These diseases can be prevented by immunisation with conjugate Hib vaccines. In South Africa, unlike some developed countries, Hib vaccines are not part of the routine immunisation schedule. The objective of this study was to measure the expected net benefits from a hypothetical programme of vaccination of the 1992 Cape Town birth cohort (N = 46,537). Costs were calculated by summing the estimated direct medical care costs together with the indirect costs of Hib disease. The latter were calculated by valuing human life using alternative, and conservative human capital and willingness-to-pay measures. The difference between Hib disease costs (i.e. the benefits which would be gained from a successful vaccination programme) and the costs of the vaccination programme itself (HibTITER, Praxis Biologicals) defined the expected net benefits. In the absence of an immunisation programme, the estimated economic costs of Hib disease in the 1992 Cape Town cohort ranged from R10.7 million to R11.8 million. The costs of introducing the vaccine would have amounted to R8.3 million. Had the vaccine been administered to the 1992 birth cohort, benefits would have exceeded costs by between R2.4 million and R3.5 million. PMID- 7784910 TI - Prevalence and incidence of blindness due to age-related cataract in the rural areas of South Africa. AB - OBJECTIVES: The Bureau for the Prevention of Blindness is responsible for the provision of cataract surgery to the rural indigent population of South Africa. It is important for the Bureau to know both the prevalence and the incidence of cataract blindness in the population. DESIGN, SETTING AND SUBJECTS: Blindness prevalence surveys were conducted in KwaZulu in 1990 and 1993. OUTCOME MEASURES AND RESULTS: The prevalence of cataract blindness was 0.59% (95% confidence interval 0.21) in 1990 and 1993. The prevalence of aphakia was 0.1% in 1990 and 0.2% in 1993, demonstrating a probable increase in the delivery of cataract surgical services, although this had not produced a demonstrable fall in the prevalence of cataract blindness. The calculated annual incidence of cataract blindness was 0.14%. CONCLUSION: Among a rural population of approximately 19 million South Africans, there is a backlog of 113,000 unoperated cataract-blind people and an incidence of 27,000 new cataract blind per year. The implications of this backlog for cataract blindness in our rural areas are discussed. PMID- 7784911 TI - Impact of a sight-saver clinic on the prevalence of blindness in northern KwaZulu. AB - The prevalence of blindness in the Ingwavuma district of northern KwaZulu was 1% (95% confidence interval 0.75 - 1.25) in 1990, and the prevalence of blindness due solely to age-related cataract was 0.39% (95% CI 0.24 - 0.54). Eight sight saver clinics were held between 1990 and 1993. Nine hundred and thirteen patients were seen and 113 cataract extractions performed at a cost of R62,000. The prevalence of blindness due solely to age-related cataract was reduced by 25% to 0.29% (95% CI 0.17 - 0.41). The overall prevalence of blindness was reduced by 4% to 0.96% (95% CI 0.72 - 1.20). The provision of aphakic spectacles to aphakic patients whose spectacles have either been lost or broken would effect a further 11% reduction to 0.85% (95% CI 0.63 - 1.07). The establishment of a permanent sight-saver clinic staffed by an ophthalmic medical assistant who is working full time in this capacity would facilitate an improvement in the delivery of eye care in the area. PMID- 7784912 TI - Inpatient care and mental handicap. PMID- 7784913 TI - Lletz look before we leep. PMID- 7784914 TI - Towards a rational cervical cytology screening strategy. Case study of a peri urban settlement. AB - OBJECTIVES: To assess cervical cytology screening activity in a peri-urban settlement near Cape Town, with a view to informing rational policy development. METHOD: Total and age-specific prevalence rates of women who had been screened, relative prevalence by age group of women who had not been screened, and yield of screening were estimated from cytopathology laboratory records and available demographic data. Age-specific prevalence rates among women who had been screened were compared with age at presentation with cervical cancer at the referral hospital. Attendance for colposcopy follow-up was assessed from colposcopy clinic records. RESULTS: The number of smears taken and the prevalence of women who had been screened peaked in the 20 - 24-year age group, and declined to low levels in those over the age of 40 years. The relative prevalence of those who had not had a smear exceeded 9 in all age groups over 39 years, compared with women of 20 - 24 years. Smears which showed signs of CIN III, malignancy or possible malignancy comprised 0.13%. Thirty-six per cent of women booked for colposcopy did not attend. CONCLUSIONS: Efficiency of screening could be improved by emphasising coverage of higher-risk age groups, e.g. women over the age of 30 years, and better follow-up. PMID- 7784915 TI - Phenylketonuria in South Africa. A report on the status quo. AB - During the 1980s a pilot newborn screening programme for the early detection (and treatment) of amino acidopathies, especially phenylketonuria (PKU), was conducted by the Department of National Health and Population Development. The motivation for this pilot programme was the high priority accorded PKU screening in Europe and North America and the presumed similarly high incidence of this condition among South Africans of European origin. From a cohort of 59,600 newborns screened in the Pretoria area over a period of 8 consecutive years (1979-1986), only 1 case of PKU (and 1 of tyrosinaemia) was found. Statistically this result is compatible (Poisson distribution, 95% confidence interval) with a 'true' incidence of not more than 3/59,600 (or about 1/20,000) newborns. It is concluded from this result and other relevant information that newborn screening for PKU and other amino acidopathies is not cost-effective and justifiable, especially against the background of prevailing demographic conditions and more pressing health priorities in South Africa. This particular screening programme was discontinued in 1986. The results and conclusions are presented here for the record. PMID- 7784916 TI - Micromanipulation at an infertility centre. AB - AIM: Human in vitro fertilisation (IVF) and gamete intrafallopian transfer have been used in the management of various forms of infertility. In cases of severe male-factor infertility, fertilisation can be a factor. In this study micromanipulation was used to increase fertilisation in such cases. METHODS: Two micromanipulation techniques, subzonal sperm injection (SUZI) and partial zona dissection (PZD), were used to assist fertilisation in patients with abnormal semen parameters. Ten couples with severe oligo-, terato- and asthenozoospermia participated in the SUZI programme. Seventy-three oocytes were obtained from these 10 patients. PZD was used on day 1 oocytes in cases of male infertility as well as a rescue attempt on day 2 oocytes when fertilisation had failed after routine insemination. RESULTS: The SUZI technique had a fertilisation rate of 37.7%. In this group, a biochemical pregnancy was achieved. Differences between the fertilisation rate of conventional IVF (33.3%) and PZD (56.3%) in cases of male infertility, were not statistically significant although a clinical difference could be detected. PZD was statistically effective in facilitating fertilisation (37.5% v. 8.3%) in couples where this procedure was introduced to reinseminate 24-hour-old unfertilised oocytes. Four patients received PZD reinseminated embryos. An average of 1.45 PZD embryos were replaced and 1 implantation pregnancy was confirmed. CONCLUSION: The micromanipulation results are encouraging and seemed to increase the efficiency of IVF in humans. Furthermore, our data support the conclusion that micromanipulation procedures can bring about pregnancies. PMID- 7784917 TI - Impoverished Africa--time to restress the value of breast-feeding. PMID- 7784918 TI - Myringoplasty--effects on hearing and contributing factors. AB - Indications for myringoplasty are chronic otorrhoea and hearing impairment. Some authors have described poor postoperative hearing results and sensorineural hearing loss associated with the surgery, and question the indication for myringoplasty on an ear with normal hearing (< 25 dB). This study of 211 consecutive myringoplasties performed over 1 year details the 'take rate,' hearing gains and losses, and factors found to influence the above. The take rate of 78% is comparable with figures in the literature. The most significant factors influencing this are the grade of the surgeon and the size of the perforation. The average pre-operative air-bone gap was closed from 23.7 dB to 13.9 dB with a 4.5% incidence of postoperative sensorineural hearing loss. Postoperatively 77.9% of patients had an air-bone gap of less than 20 dB. We conclude that myringoplasty is a beneficial procedure, closing the tympanic membrane and improving the hearing. PMID- 7784919 TI - Macrosomia--maternal and fetal risk factors. AB - Risk factors associated with fetal macrosomia were studied in 348 pregnancies resulting in the delivery of an infant weighing 4,000 g or more in a black population. Identifiable maternal risk factors included a mother in her 3rd decade of life, multiparity, maternal weight of 70 kg or more at the end of pregnancy, prolonged or post-term pregnancy, abnormal glucose tolerance and previous history of a macrosomic infant. Male infants had a higher risk of being macrosomic. Macrosomic infants accounted for 3.4% of all singleton deliveries, with their caesarean section rate of 33.9% being almost three times that of control infants. The importance of antenatal prediction of fetal weight is emphasised and suggestions for reduction of the high perinatal mortality and morbidity rates, as well as maternal morbidity, are discussed. PMID- 7784920 TI - A wolf in wolf's clothing--the abdominal compartment syndrome. AB - Four patients are described in whom massive abdominal distension after laparotomy led to increased airway and central venous pressure and severely reduced urine output. All cases were associated with massive fluid resuscitation and operative findings were a grossly oedematous bowel with free fluid under pressure in the abdomen. These findings are consistent with the diagnosis of intra-abdominal compartment syndrome. In 1 case trauma was remote from the abdomen indicating that abdominal surgery or trauma may not be a prerequisite for the development of the condition. Recognition of the features of the condition is essential as it can only be treated by decompression of the abdominal contents. PMID- 7784921 TI - An update on AIDS. PMID- 7784922 TI - Inadequate seals on enflurane bottles. PMID- 7784923 TI - 'A cervical smear, please!'. PMID- 7784924 TI - WHO cervical cytology screening guidelines--how relevant to us? PMID- 7784925 TI - Pioneering in modern ophthalmology in South Africa. PMID- 7784926 TI - Laparoscopically assisted vaginal hysterectomy--gimmick or gain? PMID- 7784927 TI - Laparoscopic versus open cholecystectomy. PMID- 7784928 TI - Last virologically confirmed cases of wild-type poliomyelitis in South Africa. PMID- 7784929 TI - Schizophrenia and prenatal influenza exposure. PMID- 7784930 TI - HIV testing and informed consent. PMID- 7784931 TI - HIV testing and informed consent. PMID- 7784932 TI - Active STDs at rural community clinics in KwaZulu. PMID- 7784934 TI - Food allergy and chronic disease--a link to keep in mind. PMID- 7784935 TI - Genetics, primary health care and the Third World. PMID- 7784933 TI - The syndromic management of genital ulcer--a note of caution. PMID- 7784936 TI - Should routine screening of neonates for deafness be introduced in South Africa? PMID- 7784937 TI - The epidemiological basis for cervical cancer screening. PMID- 7784938 TI - [Evaluation of 3 automatic systems for measurement of the erythrocyte sedimentation rate]. AB - PURPOSE: To evaluate three automated devices for measuring the erythrocyte sedimentation rate (ESR) (VES-MATIC 60, Menarini(R); SEDISCAN Becton-Dickinson(R) y SEDIMATIC, Ral(R)) by comparison with the Westergren method (WM). MATERIAL AND METHODS: A total of 1576 whole blood samples (VM: 694, SC: 316 and SM: 566) from patients of the Hospital Clinic i Provincial de Barcelona were included in this study. In all the specimens, the ESR was determined following the ICSH recommendations (WM). The Student's t test for paired data and linear regression analysis were used for inaccuracy study. Reproducibility was assessed after five measurements of three different samples and establishing the coefficient of variation (CV). RESULTS: Significant correlation was found between the systems studied and th WM. Moreover, for ESR > 21 mm/h (groups II, III and IV) the results provided by VM system were not significantly different from those of WM. Finally, all the systems presented a good reproducibility, although the lower values of CV were obtained with the VM method. CONCLUSIONS: The automatic systems for measurements of the ESR demonstrate important advantages and, from this analysis, we concluded that the VM could be the alternative method to conventional Westergren for the ESR determination. PMID- 7784939 TI - [Relationship between HLA antigens and the HIV infection in patients from the state of Zulia]. AB - PURPOSE: Some genetic factors associated to the HLA system phenotypes may allegedly predispose to the development of infection in patients exposed to the human immunodeficiency virus (HIV). So the aim of this study was to assess if certain HLA antigens are positive or negative risk factors in the development of AIDS in Zulia State. PATIENTS AND METHODS: A total of 62 samples were studied, 31 from HIV seropositive subjects and 31 form healthy individuals. The patients were subclassified into four groups in accordance with Atlanta's CDC guidelines. Tests for histocompatibility including HLA-A-B-C, DR and DQ typing were performed with Terasaki's technique. VIH positivity was determined by ELISA and confirmed by Western Blot. The statistical evalub1p4n was performed with the chi 2 test for antigen frequency comparison, the relative risk (RR) was estimated with the Ryder and Svelgaard test, and the inferential analysis was made by means of non parametric statistics. RESULTS: Most patients were included in CDC's groups II and IV, 48.4% and 29.0%, respectively. Increased B35 and DQw2 and decreased B39 and DR2 antigens were found when comparing the HLA distribution in the sample and the antigenic frequency of the population. RR > 1 was observed in the infected patients A for A1, A3, A10, A11, B5, B7, B12, B14, B35, B61, CW4, DR4, DRW52 and DQW2 HLA antigens. A positive association between symptomatic infected patients and antigen B35 was present (X = 7.045). CONCLUSION: The findings reported here suggest that antigen B35 is a major risk factor for the development of AIDS. PMID- 7784940 TI - [Treatment with fludarabine of chronic refractory lymphoid leukemia]. AB - PURPOSE: New antimetabolic drugs, purine-analogous, have been introduced in the treatment of advanced or refractory cases of chronic lymphocytic leukaemia (CLL), fludarabine (FLU) being one of such drugs. The results attained with FLU in 6 cases of refractory CLL are reported. PATIENTS AND METHODS: The efficacy and toxicity of FLU was evaluated in 6 patients (median age 63 years) between March 1993 and March 1994. Five patients were in stage III-IV and one in stage II of the Rai's system, and they were refractory to the usual treatment. The dosis used here was 30 mg/sq m/day, for 5 days every 4 weeks, up to a total of 6 therapeutic courses. The response was assessed after 3 and 6 courses. Anti-infectious prophylaxis was made with co-trimoxazole, monthly benzathine penicillin G and isoniazid in Mantoux-positive patients. The response criteria were those given by the NIC Working Group for CLL. RESULTS: The patients received 2 to 6 courses. None of them attained complete remission: 1 had nodular remission, 2 had partial remission, 2 responded partially although not reaching criteria for partial remission (1 died of pancytopenia), and 1 had disease progression and died after the second course. Fast and important reduction of the lymphocyte count as well as the CD4 lymphocytes was present in all cases. Bone-marrow infiltration decreased strikingly in 2 cases and the platelet count improved in 3 cases and worsened in 2 others. The following toxicity was recorded: 2 patients had nausea, 5 had neutropenia (below 500 x 10(9)/L in 3 instances) and 4 had thrombocytopenia (lower than 40 x 10(9)/L in one case). In 26 therapeutic courses there were 10 febrile episodes (1 for pneumonia, 1 for gastroenteritis and 8 without any septic foci); 1 patient developed pulmonary tuberculosis after completing the treatment and one patient died of posttransfusion graft versus host disease after splenectomy once she had completes six courses. CONCLUSION: This experience confirms the efficacy of FLU in the treatment of refractory B-CLL patients and is in agreement with previous reports as no response is initiated after the 3rd course. The lymphocyte count decreases quickly and strikingly. Depletion of CD4 lymphocytes along with neutropenia and hypogammaglobulinaemia make these patients highly sensitive to all types of infection, chiefly by opportunistic germs, so adequate anti-infectious prophylaxis is of great importance. The two patients with pre-treatment haemoglobin and platelet values lower than 10 g/dL and 40 x 10(9)/L, respectively, were the only ones in need of transfusion. No cumulative myelosuppression was appreciated. PMID- 7784941 TI - [Evaluation of the hematologic autoanalyzer Coulter Maxm]. AB - PURPOSE: To evaluate the performance of the Coulter MaxM autoanalyser, based on volume, cell conductivity and laser-beam dispersion, and to assess the automated leucocyte differential count (LDC). MATERIAL AND METHODS: A total number of 2,016 blood samples drawn on tri-K EDTA as anticoagulant were studied. The following data were analysed: 1-Intra- and inter-assay inaccuracy, the findings being expressed as mean and variation coefficient (CV%). 2- Correlation with the results attained with other systems (Coulter STKS and Technicon H1); The Pearson's correlation coefficient was used for this analysis. 3- Assessment of the morphologic suspect warning flags, optic microscope examination being used as reference. 4- Stability of the samples along time; the samples were analysed at 2, 6, 24 and 48 hours after withdrawal, and the Scheffe's test was used for comparison of results. 5- Performance speed. RESULTS: 1- The intra-assay inaccuracy was found acceptable for all the values except the basophil count (CV: 30.8%). The lack of reproducibility for basophil count is similar to that observed in the Coulter STKS system. 2- Correlation: Optimal LDC was found for neutrophils, eosinophils and lymphocytes. Excellent correlation with the Coulter STKS was seen except for haemoglobin, haematocrit and basophil count. The correlation with the Technicon H1 was better then with the STKS, except for basophil and monocyte counts. The correlation with basophil count was low with every system. 3- Warning flags appeared in 13.4% of the samples, the worse results corresponded to basophils, monocytes, stabs and atypical lymphocytes. 4- Samples stored at 4 degrees C for 24 hr had not significant variations in LDC. Those ones stored at 20-25 degrees C only showed significant variations after 24 hr in the monocyte count. 5- The working speed was 60 samples processed and printed in one hour. CONCLUSION: The Coulter MaxM autoanalyser is a useful machine for laboratories and provides a 5-class LDC plus a sound screen for leucocyte morphologic anomalies. PMID- 7784942 TI - [Circulating thrombomodulin: current knowledge and future prospects]. PMID- 7784943 TI - [Significance of blood components in oxidative stress]. PMID- 7784944 TI - [Production of specific antibodies against isoforms of the beta subunit of human Na,K-ATPase]. AB - The study of the differential and functional tissular distribution of the isoforms of Na,K-ATPase, an enzyme located on the plasma membrane of animal cells, must be performed with the aid of antibodies capable of specifically recognising beta 1 and beta 2 subunits. In order to facilitate the study of the functions and distribution of such isoforms, proteins were generated using pET series plasmid construction and transformation in E coli bacteria, and their production was promoted with IPTG, these being the antigens that induce antibodies specific for each isoform. The antisera thus obtained were used in Western Blot assays with tissue microsomes from different animal species; specifically, beta 1 and beta 2 isoforms of Na,K-ATPase could be recognised. A panel of polyclonal antibodies was obtained which proved capable of recognising these isoforms in different animal species, as well as their deglycosylated isoform. Such antibodies can be used as an efficient tool for functional and tissue distribution studies of the two isoforms. PMID- 7784945 TI - [Richter syndrome: morphologic transformation with persistence of the same phenotype]. AB - Richter's syndrome is termed as the occurrence of a high-grade lymphoma along with a chronic lymphocytic leukaemia. We report a patient diagnosed as having a CLL evolving into an immunoblastic lymphoma. In spite of this morphologic change, the same identical immunophenotype remained in both types of cells assessed, that is, CLL-type lymphocytes and immunoblastic and lymphoplasmocytoid cells. This event appears to favour the common clonal origin of these two entities. PMID- 7784947 TI - [External evaluation of the quality of visual count if reticulocytes: 4 years' experience]. PMID- 7784946 TI - [Idiopathic myelofibrosis with extramedullary hematopoiesis foci in the skin and testicles. Report of a case]. AB - Idiopathic myelofibrosis (IMF) is a clonal chronic myeloproliferative syndrome characterized by the proliferation of the three haemopoietic series and the marrow connective tissue and by the development of extramedullary haemopoiesis in the liver, spleen and lymph nodes. Cutaneous extramedullary haemopoiesis is an uncommon event and we could not find any reported cases of testicular involvement in this disease. We report the case of a 28 year-old male with diagnosis of idiopathic myelofibrosis in November 1988. During the course of the disease, three years later, he developed a tumor on his right testis. Histologic examination showed extramedullary haemopoiesis with cells of the myeloid, erythroid and megakaryocyte series, in the interstice. Eight months later, numerous red-purple papules and nodules developed on the patients's trunk. The biopsy of a skin lesion revealed an infiltration of the dermis by myeloid, erythroid cells and few megakaryocytes. The patient's clinical condition worsened, and he died in February 1993 following progressive deterioration of the general condition. We describe a case of IFM with extramedullary hemopoiesis involving the skin and the testis pointing out the rarity of these localization. PMID- 7784948 TI - [Fever caused by myeloma or brucellosis? Overlapping of 2 entities]. PMID- 7784949 TI - [Paraparesis caused by epidural granulocytic sarcoma in a non-leukemic patient]. PMID- 7784950 TI - [Lymphocytotoxic antibodies in blood donors. Relationship with HIV antibodies at the blood bank of the state of Zulia-Venezuela]. PMID- 7784951 TI - [Hematology at local hospitals. An option with a future? Workshop on Hematology of the Local Hospitals of Catalonia]. PMID- 7784952 TI - [Hematology: a specialty in crisis?]. PMID- 7784953 TI - [Blood fractionation based on the extraction of the buffy-coat layer. Analysis of our results]. AB - PURPOSE: To compare a procedure of blood processing via a quadruple bag for the preparation of white-cell-poor blood components with the results obtained with triple-bag-system, in order to adopt it as routine in our blood centre. MATERIAL AND METHODS: Blood was collected in 289 quadruple-bag-system containing 63 mL of CPD as anticoagulant and 100 mL of SAG M solution as additive for the red cells. We used 237 standard quadruple-bags supplied by Fenwal (195) and NPBI (42), and 52 of the top-and-bottom system supplied by Fenwal. Blood separation was made automatically by CompomatR (NPBI) and platelet concentrates were prepared from the buffy-coat fraction. Standard bags were processing as follows: After the first centrifugation of the whole blood (28,800 g), the plasma was transferred into the 300-mL bag until the interface of red cells and plasma was detected; then approximately 80 mL of plasma and buffy-coat (BC) were collected into the 100-mL satellite bag. Top-and-bottom bags were centrifuged at 43,500 g., the red cells were transferred into the bottom-bag containing SAGM, and plasma was transferred into the top-bag. The buffy-coat fraction remains in the original bag. In both procedures, platelet concentrates were prepared from buffy-coat fraction. After the centrifugation of this fraction (1,400 g and 1,600 g), the supernatant (concentrated platelets in plasma) was transferred into a 300-mL bag and the bag with the residual buffy-coat was then discarded. 287 triple-bags were separated in the traditional way, using platelet-rich plasma (PRP) as a source for the preparation of platelet concentrate (PC). Volumes were measured by weigh and specificity gravity. Platelet, leukocytes and red-cells were counted in the Coulter-Counter (STKR.Izasa). T-Student test and Chi2 test were used for statistical analysis and p < 0.05 was taken as a significant difference between samples. RESULTS: The three kinds of quadruple-bags showed results very homogeneous with little differences. For all brand of bags packed-red-cells showed a volume of 300 +/- 2.9 mL, EVF of 51.9 +/- 0.7%. The recovery of red cells into the packed red cells and of platelets into the platelet concentrate was 90 +/- 0.4 percent and 69 +/- 2 percent respectively, of the original value. White cells in the packed red cells were 9.7 +/- 03 x 10(9) with recovery of 30.1 +/- 1.4 percent of the original value; statistical difference was found in comparison with triple bags PRC (p < 0.001). The PC volumes averaged 71 +/- 1 mL and the overall mean platelet concentration was 77 +/- 2 x 10(9). Eighty three percent of PC contained more than 55 x 10(9). White cells contamination of platelet concentrates was 0.283 +/- 0.039 x 10(9), with a recovery of 9.5 +/- 1.5 percent of the leukocytes present in the whole blood. This value is below the threshold that prevents febrile reactions and microaggregate formation. The plasma yield in the quadruple-bag system was much greater than that in the triple bag system (p < 0.001). With this process we removed about 77 +/- 0.5 percent of the plasma present in the original unit in comparison with 56 +/- 1 percent removed in that of the triple-bag system. CONCLUSION: With this procedure leukocyte-poor blood components are obtained in which more of 90 percent original white cells have been removed, with a red-cell recovery of 90 percent. Moreover, the plasma yield is also excellent. PMID- 7784954 TI - [Age and racial geographic distribution of S hemoglobin in Brazil]. AB - OBJECTIVES: This paper was meant to analyse distribution of HbS carriers in Brazil, comprising its regional prevalence and the relationship with racial settlement and age groups. MATERIAL AND METHODS: 67,667 blood samples from 48 Brazilian towns were analysed from 1976 to 1988. Such samples were classified as Caucasoid and Negroid. The diagnosis was defined by means of qualitative electrophoresis in alkaline and acid pH, quantification of haemoglobin fractions, cytological studies and some cases were confirmed after examination of the parents. RESULTS: The study of those 67,667 samples allowed us to detect 1,492 HbS carriers (2.2%). That frequency is higher among Negroids (5.16%) than among Caucasoids (1.22%): Z = 22.1397 (Zcritical; 0.05 = 1.9600). Taking the HbS carrier distribution into consideration, we noticed that it is relatively homogeneous among Negroids and higher than 5% in 9 out of the 16 areas involved in the study. By classifying the age group of the areas in the general sample and by comparing the proportions, we found out that there are significant differences (chi 2 = 50.88; chi 2 critical; 0.05; 5 gl = 11.070). CONCLUSIONS: Sickle-cell anaemia diseases play an important role among the pathologies found in several countries, including Brazil. This paper shows that the carriers prevalence varies in the several areas under study and is higher among Negroids in almost all of them. The decreasing frequency occurring from North to South in the general samples and among Caucasoids may be assigned to the contribution of the Negroes in the interracial crossing, particularly in the Northeast. PMID- 7784955 TI - Forskolin induces preproenkephalin and preprodynorphin mRNA in rat striatum as demonstrated by in situ hybridization histochemistry. AB - Cyclase response elements (CREs) are located in the promoter regions of several neuropeptide and immediate early genes. Activation of the adenylate cylase/cAMP second messenger cascade leads to phosphorylation of CRE-binding proteins (P CREBs) which bind to CREs in the promoter regions of these genes and alter their rate of transcription. We have previously reported an increase in striatal immunoreactivity for P-CREB (phosphorylated on Ser-133) and Fos following intracerebroventricular (ICV) injection of H2O-soluble forskolin, a direct activator of adenylate cyclase. Because CREs are located in the promoter regions of the opioid peptide genes, preproenkephalin (PPE) and preprodynorphin (PPD), we investigated what effect continuous ICV infusion of H2O-soluble forskolin has on striatal PPE and PPD mRNA levels. Quantitative in situ hybridization histochemistry demonstrated that continuous activation of the adenylate cyclase/cAMP second messenger cascade results in a significant induction of striatal PPE and PPD mRNA at 6, 24, and 72 h. The sustained induction of striatal PPE and PPD mRNA indicates that pro-opioid gene transcription is not desensitized following 72 h of continuous adenylate cyclase activation. Continuous ICV infusion of 1, 9-dideoxyforskolin, a forskolin analog which does not activate adenylate cyclase, did not induce striatal PPE and PPD mRNA. These data are consistent with cAMP-dependent protein kinase-induced phosphorylation and binding of CREBs to CREs in the promoter regions of pro-opioid genes during sustained activation of adenylate cyclase. PMID- 7784956 TI - Neuropeptide Y and dynorphin-immunoreactive large dense-core vesicles are strategically localized for presynaptic modulation in the hippocampal formation and substantia nigra. AB - Neuropeptide Y (NPY) and dynorphin elicit regionally selective presynaptic modulation in the hippocampal formation and the pars reticulata of the substantia nigra, respectively. We examined potential anatomical substrates for their presynaptic modulation by determining the distribution and size of large (80-120 nm) dense-core vesicles (DCVs), organelles previously shown to be immunoreactive for each peptide. Throughout the hippocampal formation, NPY-immunoreactive DCVs were located primarily in axon terminals and were more sparingly distributed in dendrites. In comparison with other portions of the hippocampal formation, NPY labeled DCVs were most abundant in axons and terminals of the CA1 region. The DCVs in the CA1 region of the hippocampus also more frequently had larger mean cross-sectional diameters when located along portions of the terminal in contact with unlabeled axons. In both the CA1 region of the hippocampus and the dentate gyrus, NPY-labeled DCVs in contact with portions of the axonal membrane apposed to astrocytes also were larger than those located more centrally in the axon terminal. Dynorphin-immunoreactive DCVs in axon terminals of the substantia nigra were significantly larger when found near portions of the axonal membrane in contact not only with other axons and astrocytic processes, but also occasionally with postsynaptic dendrites. The parallels between diameters of DCVs and known selectivity of NPY for presynaptic modulation in the CA1 region of the hippocampus suggest a direct correlation between the size and distribution of immunoreactive DCVs and their sites of exocytotic release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784957 TI - Evidence for 5-HT autoreceptor-mediated, nerve impulse-independent, control of 5 HT synthesis in the rat brain. AB - To gain further insight into the operation of 5-HT autoreceptor-mediated feedback control of 5-HT biosynthesis in serotonergic nerve terminal areas, the effect of the 5-HT1B and the 5-HT1A receptor agonists, TFMPP and 8-OH-DPAT, respectively, were investigated in the rat central nervous system (CNS) using in vivo and in vitro neurochemical approaches. TFMPP suppressed 5-HT synthesis (5-HTP accumulation after decarboxylase inhibition) both in vivo and in vitro. In vivo, the 5-HT synthesis-suppressing effect of the drug (3.0 mg/kg, s.c.) proved resistant to either acute hemitransection or reserpine (5 mg/kg, i.p.; 90 min before) pretreatment. In vitro, in cortical, hippocampal and striatal slice preparations, TFMPP (0.1-10 microM) decreased 5-HT synthesis under basal and stimulated (30 mM K+) conditions, an effect which was unaltered by prior in vivo reserpine-induced 5-HT depletion but was attenuated in the presence of 5-HT1B receptor antagonists such as methiothepin, cyanopindolol or propranolol. The 8-OH DPAT (0.1 mg/kg, s.c.)-induced decrease of 5-HT synthesis in vivo was abolished by hemitransection but resistant to acute reserpine pretreatment; 8-OH-DPAT (10 microM) did not decrease 5-HT synthesis in vitro. In conclusion, the present study confirms the importance of 5-HT autoreceptors in the feedback control of nerve terminal 5-HT biosynthesis. Specifically, our data indicate: (1) that the reduction of rat brain 5-HT synthesis after TFMPP is mediated by 5-HT1B autoreceptors located on the serotonergic axon terminals, and (2) that the effect is directly mediated and occurs independently of 5-HT neuronal firing and intact monoamine stores. PMID- 7784959 TI - Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes. AB - Experiments were performed to examine neurochemically the functional diversity of GABAA receptors as measured by muscimol-, 5 alpha-pregnane-3 alpha,21-diol-20-one (THDOC)-, and pentobarbital-stimulated 36Cl- uptake, and region-specific changes in muscimol-, THDOC- and THDOC-induced potentiation of muscimol-stimulated 36Cl- uptake in rats treated acutely or subacutely with a subconvulsive dose of bicuculline. The data for stimulation of 36Cl- uptake by muscimol showed a single binding site interaction in the cerebral cortex, hippocampus and cerebellum. The concentration-response curves for muscimol in the cerebral cortex and hippocampus were steep and indicated an increase of approximately 130% at the maximum concentration. In contrast, the curve for the cerebellum was shallow and exhibited a smaller maximal response (approximately 60%). Apparent affinity for muscimol also differed among these brain regions. The regional differences in 36Cl- uptake induced by THDOC and pentobarbital were not as apparent as those induced by muscimol; however, the maximal modulatory effect of pentobarbital in the hippocampus was significantly higher than that in the cerebellum. In rats treated subacutely with a subconvulsive dose of bicuculline, a significant increase in muscimol-stimulated 36Cl- uptake was observed in the cerebellum but not in the frontal cortex or hippocampus. Analysis of the concentration-response curves for muscimol-stimulated 36Cl- uptake in the cerebellum revealed that the Vmax for muscimol in the subacutely treated group was significantly higher than those for muscimol in the control and acutely treated groups without any differences in the KD value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784958 TI - PET imaging studies of dopamine D2 receptors: comparison of [18F]N methylspiperone and the benzamide analogues [18F]MABN and [18F]MBP in baboon brain. AB - A series of positron emission tomography (PET) imaging studies was conducted in a baboon with the benzamide derivatives [18F]2,3-dimethoxy-N-[9-(4-fluorobenzyl)-9 azabicyclo[3.3.1]non an-3 beta-yl]benzamide ([18F]MABN) and [18F]2,3-dimethoxy-N [1-(4-fluorobenzyl)piperidin-4-yl]be nza mide ([18F]MBP). Studies were also conducted with the butyrophenone [18F]N-methylspiperone (NMSP) for comparison. Tissue-time activity curves of [18F]MABN are similar to those of [18F]NMSP since both compounds displayed approximately the same uptake in the basal ganglia and displayed irreversible binding kinetics in vivo. However, the rapid rate of clearance from the cerebellum and high basal ganglia:cerebellum ratio of [18F]MABN indicate that this compound has a much lower amount of nonspecific binding than [18F]NMSP. [18F]MBP displayed a higher uptake in the basal ganglia relative to [18F]NMSP and [18F]MABN and exhibited reversible binding kinetics in vivo. This property of [18F]MBP is desirable since the uptake of radioactivity in D2-rich ligands is less likely to be influenced by changes in cerebral blood flow. The current data suggest that both [18F]MABN and [18F]MBP are promising ligands for studying dopamine D2 receptors with PET. PMID- 7784960 TI - Long-lasting inhibition of in vivo cocaine binding to dopamine transporters by 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester: RTI-55 or beta CIT. AB - Cocaine analogs such as 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) with a higher affinity for the dopamine transporter (DAT) may be potentially useful in interfering with cocaine's actions in brain. This study evaluates the time course of the effects of RTI-55 on cocaine binding in baboon brain using PET and [11C]cocaine. [11C]Cocaine binding was measured prior to, and 90 minutes, 24 hours, 4-5 days and 11-13 days after RTI-55 (0.3 mg/kg i.v.). Parallel studies with [3H]cocaine and RTI-55 (0.5 mg/kg i.v. or 2 mg/kg i.p.) were performed in the mouse. RTI-55 significantly inhibited [11C]cocaine binding at 90 minutes and 24 hours after administration. The half life for the clearance of RTI-55 from the DAT was estimated to be 2 to 3 days in the baboon brain. In the mouse brain, RTI-55 significantly inhibited [3H]cocaine binding at 60 and 180 minutes after administration and recovery was observed at 12 hours. These results document long-lasting inhibition of cocaine binding by RTI-55 and corroborate that binding kinetics of RTI-55 in striatum observed in imaging studies with [123I]RTI-55 represents binding to DATs. PMID- 7784961 TI - Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: alterations during rat amphetamine withdrawal and following chronic injection stress. AB - Transcription factors are known to act as gene expression regulators, possibly linking extracellular stimuli to long-term modifications at the neuronal level. Such modifications may potentially underlie chronic psychostimulant- and stress induced behavioral alterations. This study illustrates how a 2 week, twice daily 7.5 mg/kg d-amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including c-fos, fos-B, jun-B, c-jun, and zif 268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses. Amphetamine withdrawal induced decreases in transcription factor mRNA levels, assessed using Northern blot analysis, appear most prominent in prefrontal cortex, begin approximately 12 h after the last injection, and largely recover to control levels by 54 h. Prefrontal cortical and striatal dopamine content, assessed using HPLC, decrease and recover over a similar time course. Behavioral "stereotypy time" manifest by animals exposed to a novel environment, a measure sensitive to psychostimulant withdrawal, also decreases beginning 12 h after the last injection, is still significantly reduced at 54 h, and recovers at 72 h. Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a "rebound" increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short-lived increase in striatal dopamine turnover. At the same time, rats display much longer-lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection. The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor-mediated gene expression in neurochemical mechanisms underlying psychostimulant withdrawal and chronic injection stress-induced behavioral alterations. PMID- 7784963 TI - [Therapists and therapeutic service during World War II]. PMID- 7784962 TI - Biological mechanisms and perinatal exposure to abused drugs. AB - Use of illicit and licit drugs during pregnancy is a major public health concern, as it can have adverse effects on the developing fetus. Infants born of women addicted to narcotics, cocaine, alcohol, or polydrugs often undergo a characteristic withdrawal syndrome and may have physical, behavioral, and/or neurological abnormalities. As it is not feasible to ascertain whether these functional changes in human infants are produced by abused substance(s) per se or by a combination of complex socioeconomic factors and polydrug use, researchers in recent years have developed and utilized various innovative animal models to assess drug-induced alterations and their biological mechanisms during the developmental period under a controlled environment. To promote interdisciplinary communications as well as to assess the progress and the future needs in this area, the National Institute on Drug Abuse (NIDA) held a technical review at which biomedical researchers discussed their current findings in various physiological systems. This report summarizes the major findings and the methodological and experimental issues discussed at the conference. The meeting was held in Washington, DC, on May 25 and 26, 1994. PMID- 7784964 TI - [In the last year of the war (the notes of a therapist in mobile surgical field hospital No. 200)]. PMID- 7784966 TI - [Medicine of the twentieth century. The evolution of diagnosis]. PMID- 7784965 TI - [The organizers of therapeutic operations in World War II 1941-1945 (on the 50th anniversary of a great victory)]. PMID- 7784967 TI - [Magnetic resonance tomography in hydronephrotic transformation, cystic lesions and tumors of the kidneys in patients with arterial hypertension]. AB - MR tomography was carried out on MR tomographs Tomicon 1100 (Bruker, 0.23 T) and Magnetom SP 63 (Siemens, 1.5 T) in 126 hypertensive subjects (66 had cysts, 20 HT and 31 renal tumors) and 27 healthy controls. MR tomography proved highly specific and sensitive in diagnosis of renal new growths. In complicated cases additional information can be provided by paramagnetic contrast examinations. MR tomography as an on demand diagnostic method is recommended for use in a two stage check-ups of patients with arterial hypertension. PMID- 7784968 TI - [The characteristics of the intracardiac hemodynamics in hypertrophic cardiomyopathy: the role of cine-magnetic resonance tomography]. AB - Cine-magnetic resonance (CMR) tomography was assessed for ability to determine cardiac function and structure in patients with hypertrophic cardiomyopathy (HTCM). CMR tomography findings were compared to those of two-dimension and doppler-echocardiography, cardiac catheterization. The trial entered 16 patients with obstructive, 22 patients with nonobstructive HTCM and 14 healthy controls. CMR tomography was performed on a superconducting tomograph (1.5 T) in synchronism with ECG. CMR tomography helped detect obstruction for the blood outflowing from the left ventricle. This was impossible with the use of spin echo. It also defined area and volume of low-intensity regions. CMR tomography proved sensitive in bringing out mitral regurgitation, the results being close to those of doppler-echocardiography. Opportunities of MRT in HTCM gets expanded in cine-regimen as it provides additional information on cardiac function and intracardiac hemodynamics. PMID- 7784970 TI - [The clinico-hemodynamic effects of the antioxidant ceruloplasmin in IHD patients]. AB - Ceruloplasmin- and placebo-treated CHD patients were studied for severity of angina pectoris, changes in central hemodynamics, exercise tolerance. It is shown that ceruloplasmin promoted an increase in exercise tolerance, higher quality of life, arrest of the disease progress. Combined treatment of CHD incorporating ceruloplasmin produced a positive effect on central hemodynamics and contractile, pump capacities of the myocardium. PMID- 7784972 TI - [Ultrasonic methods in evaluating the blood supply of the kidney. The characteristics of normal renal blood flow]. PMID- 7784971 TI - [Predictors of coronary artery restenosis in IHD patients after transluminal balloon coronary angioplasty]. AB - To determine clinical and angiographic predictors of restenosis after successful PTCA, we analysed the data on 63 patients (68 stenoses) who had undergone repeat coronary angiography during the first eight months after successful PTCA. The overall restenosis rate was 42.6%. Four clinical and angiographic factors were associated with high risk of restenosis. Residual stenosis > or = 25% was the strongest predictor of restenosis (p = 0.002). Among other factors presence of unstable angina, complicated lesion morphology and absence of intimal dissection had equal value of significance (p = 0.02 in all the cases). PMID- 7784969 TI - [The assessment of left ventricular diastolic function in patients with systemic scleroderma by radionuclide ventriculography]. AB - To assess left ventricular (LV) diastolic function in scleroderma systematica (SS) with regard to SS course and skin lesion degree, a total of 24 SS patients were examined versus control subjects. Though cardiac symptoms manifested clinically only in 8 patients, parameters of LV diastolic function underwent changes in the majority of the examinees: the time to attaining maximal filling velocity increased, contribution of the first diastolic third to LV filling diminished, hemodynamic significance of the left atrial systole grew. More pronounced dysfunction of the myocardium occurred in patients with diffuse skin lesions, acute and subacute disease who also appeared to have reduced LV ejection fraction. The conclusion is made on frequent subclinical pattern of myocardial involvement in SS patients which runs primarily as LV diastolic dysfunction. Systolic disturbance emerge later or in more active forms. PMID- 7784973 TI - [The formation and development of therapeutic care during World War II]. PMID- 7784975 TI - [The first experience in Russia of using DNA diagnosis in Alport's syndrome in a family with a unique morphological picture of the kidney lesion]. AB - Clinicomorphological findings are reported for two children from families with hereditary predisposition to hematuria characterized by early occurrence of chronic renal insufficiency, neurosensory hypoacusis, congenital ocular abnormalities inherited by sex-linked dominant type. Light microscopy of nephrobiopsies revealed diffuse mesangial proliferation in both children. Final diagnosis of Alport's syndrome was feasible only on molecular-genetic level after polymerase chain reactions had identified mutation in collagen type 4 alpha-5 chain gene on a long arm of X-chromosome in genotypes of both patients and their mothers. Genetical, clinical, morphological, evolutional and diagnostic aspects of Alport's syndrome are reviewed. PMID- 7784974 TI - [The venous occlusion test in assessing the fibrinolytic activity of the vascular endothelium in lupus nephritis patients]. AB - A venous occlusion test was used to evaluate the reserves of the kidneys and that of vascular endothelium fibrinolytic activity (VEFA) in patients with lupus nephritis (LN). Prior to and following venous occlusion functional activity of plasminogen activators in plasma and urine (PAPU), plasma activity of antiactivator (PAAA), urokinase urine activity (UUA) were measured by fibrin plate lysis test in 24 patients with active LN, 6 SLE patients with intact kidneys, 10 healthy subjects. Venous occlusion test revealed normal reserve of plasma activator activity in mild LN and depletion of this reserve in LN patients with nephrotic syndrome and rapidly progressive LN. In the latter patients PAPU and PAAA were suppressed. PAPU reserve existed in all the patients, but those with rapidly progressive LN. UUA in LN was close to normal and did not change significantly after venous occlusion. The data obtained suggest that patients with severe LN had reduced reserves of VEFA, while in those with progressive LN there were also diminished reserves of renal fibrinolytic activity reflecting the severity of endothelial lesion. PMID- 7784976 TI - [Postcoital allergy: the possibilities for a specific diagnosis]. PMID- 7784977 TI - [Lipid peroxidation markers in the exhaled breath and microsomal oxidation in patients with chronic diffuse liver diseases]. AB - Low-molecular hydrocarbons (butan, pentan) from the exhaled air as lipid peroxidation (LPO) markers were quantified in patients with chronic diffuse liver diseases. The study was also made of microsomal oxidation enzymic activity by antipirin metabolism. The above parameters were followed up in the course of antioxidant treatment. As shown by total butan and pentan levels, LPO activity varied with the disease, being high in hepatic cirrhosis and primary biliary cirrhosis, but low in chronic active hepatitis and fat dystrophy. Increased levels of butan and pentan occurred in association with inhibited activity of P450-dependent monooxygenases. This was determined by antipirin biotransformation and confirmed by a strong inverse correlation between the amount of hydrocarbons and antipirin metabolites (4-hydroxy- and norantipirin) clearance. In the course of antioxidant therapy the most pronounced inhibiting action on formation of low molecular hydrocarbons was distinctive of essenciale, pikamilon and copmplivit. Relevant efficacy of carsil was weaker. Similar regularity for these drugs takes place in relation to activation of microsomal oxidation. PMID- 7784978 TI - [The conservative treatment of thrombophlebitis of the surface veins of the lower extremities]. AB - Clinical presentation of acute thrombophlebitis affecting lower limbs, classification of its forms and the response of the patients to essaven-gel are reviewed. Indications to such treatment are provided. High efficacy of essaven gel is stated. PMID- 7784979 TI - [Pneumatic balloon dilatation using a Rigiflex dilator in the treatment of patients with achalasia]. PMID- 7784981 TI - [The genetics of intermediate phenotypes in hypertension]. PMID- 7784980 TI - [Prognostic criteria for the clinical course of systemic lupus erythematosus]. AB - To develop some individual prognostic criteria of SLE clinical course the Wald's analysis of immunogenetic markers (HLA) was used. The obtained summarized diagnostic coefficients allow predicting a subacute or chronic pattern of the disease, the rate of generalization and the most frequent location of the process in certain organs. The constant character of HLA-typing results and the simplicity of the given prognostic tables made the proposed diagnostic method convenient for medical practice. PMID- 7784982 TI - [Enzyme autoantibodies--the key to the more specific diagnosis of autoimmune diseases]. PMID- 7784983 TI - [Rapidly progressing glomerulonephritis]. PMID- 7784984 TI - [The early diagnosis of kidney failure in diabetic patients and the new developments in its treatment]. PMID- 7784985 TI - [The basic trends in the research on and treatment of chronic obstructive lung diseases. The Working Group of the Canadian Thoracic Society]. PMID- 7784986 TI - [The drug treatment of gastric and duodenal peptic ulcer]. PMID- 7784987 TI - [The ultrasonic diagnosis of a mycotic aneurysm of the superior mesenteric artery in a patient with infectious endocarditis]. PMID- 7784988 TI - [Cases of the outpatient diagnosis and treatment of Horton-Magath-Brown disease]. PMID- 7784989 TI - [A case of relapsing febrile nonsuppurative panniculitis]. PMID- 7784992 TI - [Cystic kidneys (autosomal dominant polycystic kidney disease)]. AB - Polycystic kidney disease is a rather common genetic disorder, with an estimated amount of 8 to 10% of patients in the dialysis population. Meanwhile the defective gene of autosomal dominant polycystic kidney disease [ADPKD], another common terminus for this disorder, has been localized on the short arm of chromosome 16. The genetic disorder is not strictly localized on the kidney, whereas other organ systems like cardiac valves, brain arteries, liver, colon, etc. may be involved in the disease process. Hypertension is an early and common feature of the disease and its probably an important factor for progression of renal failure in ADPKD. Not all carriers of the ADPKD-trait progress to endstage renal failure, about 50% at the age of 50 years. Patients with ADPKD have a good prognosis in renal replacement therapy programs such as dialysis or renal transplantation. PMID- 7784993 TI - [Therapy of primary chronic glomerulonephritis]. AB - Primary chronic glomerulonephritis may emerge clinically as acute nephritis, the nephrotic syndrome as well as asymptomatic hematuria and proteinuria. Therapeutic consequences still depend on the morphological diagnosis. In cases of minor proteinuria [< 3,5 g/24 h] immunosuppressive therapy is not superior to symptomatic therapy. In patients with nephrotic syndrome immunosuppressive therapy depends on the morphological diagnosis. Glucocorticoids are the therapy of choice in minimal changes glomerulopathy and should be tried in focal segmental sclerosing glomerulonephritis. Steroids may be tried in pure mesangial as well as in IgA and IgM nephropathy. Especially Ponticelli claims significant therapeutic success in patients with membranous glomerulonephritis treated with Prednisolone and Chlorambucil. Failures and relapses may be treated with Cyclophosphamide, Chlorambucil or Cyclosporin A. Anticoagulants may be advantageous in the therapy of membranoproliferative glomerulonephritis. PMID- 7784990 TI - [Clinical nephrology]. PMID- 7784991 TI - [Nephritic sedimentation findings]. AB - The urinary nephritic sediment represents a well defined microscopic pattern, which indicates an active renal disease or its relapse. Therefore, once a nephritic sediment is found, the physician should immediately proceed to further diagnostic steps to define the renal disease and to start treatment. PMID- 7784995 TI - [Ischemic nephropathy]. AB - Ischemic nephropathy encompasses renal insufficiency due to 3 different diseases, namely renal artery stenosis, so-called benign nephrosclerosis, and renal cholesterol embolism. All 3 disease entities may lead to a progressive loss of renal excretory function. If a patient presents with renal failure of unknown origin, renal artery stenosis should be looked for by color-coded duplex scanning or arteriography. The clinical presentation of benign nephrosclerosis in caucasians has no typical clues. Usually, a renal biopsy identifies this renal disorder in a patient with long-standing hypertension, moderate proteinuria and renal insufficiency. Cholesterol embolism typically affects several arterial trees, and is induced by arteriography in patients with arteriosclerosis of the aorta. The best treatment for ischemic nephropathy due to renal artery stenosis [conservative, angioplasty, surgery] is unknown because appropriately controlled trials are lacking. Invasive therapy should be considered in patients with bilateral renal artery stenosis or stenosis of a single functioning kidney, particularly if the affected kidney is not contracted. Arguments in favor of invasive therapy include the progressive nature of renal artery stenosis and the poor outcome of dialysis patients with this diagnosis as underlying renal disease. PMID- 7784994 TI - [Diagnosis and therapy in systemic vasculitis with renal involvement]. AB - The diagnosis of Wegener's granulomatosis, microscopic polyarteritis and idiopathic rapidly progressive glomerulonephritis as the main cause of renal involvement in systemic necrotizing vasculitis was revolutionized following the introduction of the ANCA test. The different clinical manifestations of these diseases are described. By means of the ANCA test it could be demonstrated that the pulmonary-renal syndrome was mainly caused by these vasculitides and not by Goodpasture's syndrome. Cyclophosphamide and steroids remain the drugs of choice in the treatment. They can be administered in different ways depending upon the clinical manifestation of the diseases. As therapeutic alternatives cyclosporin, trimethoprim/sulfamethoxazole, intravenous immunglobulins and monoclonal antibodies are discussed. PMID- 7784996 TI - [Acute kidney failure caused by Hantaviruses]. AB - Hantavirus-induced acute renal failure is a worldwide occurring disease and rarely known and diagnosed in Germany and in Western Europe. Its various clinical features are embraced by the term Hemorrhagic Fever With Renal Syndrome (HFRS). Cardinal symptoms of the mild European form called Nephropathia epidemica (NE) leading to diagnosis are: abrupt onset, fever, pain (abdominal, loin-, or headache), acute renal failure, proteinuria and/or hematuria, polyuria, and thrombocytopenia. Etiologic agent of NE is the vole transmitted Puumula-serotype of Hantaviruses. Severe courses of HFRS characterized by hemorrhagic complications occur in Asia and Southeast Europe and are caused by the serotypes Hantaan (Korean Hemorrhagic Fever), Seoul (rat associated) and Belgrade (both Epidemic Hemorrhagic Fever). Serological evidence of IgG and/or IgM-antibodies by indirect immunofluorescent antibody assay (IFA), enzyme linked immunosorbent assay (ELISA) or mu-capture-ELISA proves the diagnosis and allows distinction of the infecting virus type. Transmission occurs primarily through inhalation of virus contaminated aerosols or dust. Transmission between humans has never been observed. The incubation period ranges between four days to four weeks. All persons who have much outdoor activities in forests, open fields, farms, and nearby waters are at risk to be infected. Practical exposure prophylaxis seems rarely possible. Therapy of NE is only symptomatic, confined to the treatment of pain, diuretic therapy in oliguric patients, and volume and electrolyte substitution in volume depleted or polyuric patients. Sometimes temporary hemodialysis is needed. Renal history reveals commonly the pattern of acute interstitial nephritis with typical focal interstitial microhemorrhages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7784997 TI - [What should the general practitioner know about diagnosis and treatment of acute kidney failure?]. AB - Acute renal failure (ARF) is defined as a renal insufficiency of sudden onset (increase of creatinine and urea in the serum) combined with or without oliguria (less than 500 ml of urine per day). Nephrotoxins (drugs, contrast medium) or renal ischemia (hypovolemia, hypotension, shock, septicemia, treatment with CEI) may affect the renal tubulus through several pathways, all of which may result in ARF. Ultrasound allows to distinguish hydronephrosis from ARF which is characterized by increased width of the parenchyma and low echodensity of the medulla. ARF is usually reversible. If conservative therapy fails, dialysis treatment is necessary. PMID- 7784998 TI - [Conservative treatment in chronic kidney insufficiency]. AB - Modern therapeutic concepts of chronic renal insufficiency are based on observations showing a retardation of progressive renal failure by therapeutic measures. In the context emphasis is now placed on the treatment of arterial hypertension and on the patient's adherence to a protein-restricted diet. In addition to these conservative measures it is important to avoid nephrotoxins, to hydrate the patient sufficiently and to treat advanced hyperlipidemias. Deficiencies of active vitamin D should be treated by oral vitamin D substitution after correction of hyperphosphatemia. In the treatment of the latter, preparations of calcium carbonate are now the preferred mode of treatment. In advanced renal insufficiency it is important to maintain a salt-restricted diet and to treat any attendant hyperkalemia and hyponatremia. PMID- 7784999 TI - [Urinary tract infections in adults: old and current aspects]. AB - Urinary tract infections are common clinical problems. Intense research in the last decade has led to improved knowledge about the pathogenesis, diagnosis and management of these infections. Virulence factors of uropathogenic E. coli have been well defined. Factors putting the host at increased risk of infections such as behaviour in women and men and genetic determinants in women such as blood group secretor status have been elucidated. Several diagnostic studies have shown that in symptomatic women colony counts of > or = 10(2) CFU/ml [CFU = colony forming units] of urine usually indicate infection. Finally, optimal and cost effective management of urinary tract infections is now well defined based on clinical studies. We review the management of urinary tract infections in adults taking into account recent research data and some of the still controversial issues. PMID- 7785000 TI - rhDNase in cystic fibrosis. PMID- 7785001 TI - Pulmonary surfactant: unanswered questions. PMID- 7785002 TI - The consequences of chronic allergic inflammation. PMID- 7785003 TI - Medium term treatment of stable stage cystic fibrosis with recombinant human DNase I. AB - BACKGROUND: A phase II multicentre double blind placebo controlled study in 1993 showed that short term treatment (10 days) with recombinant human DNase I (rhDNase) was safe and improved pulmonary function in patients with cystic fibrosis with stable stage lung disease. A six month open label treatment study was conducted in some of the patients who participated in the short term study to assess the medium term effects of rhDNase. METHODS: Patients who completed the phase II study and were stable for 14 days prior to treatment were eligible. They were treated with rhDNase 2.5 mg twice daily for six months and reviewed at regular intervals to assess safety and efficacy. RESULTS: Fifty nine patients (31M,28F) of age range 16-55 years were recruited. Mean baseline values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were 41.5% and 72.4% of predicted, respectively. The mean increase in FEV1 over the first month of treatment was 13.1% (range 12-14.1%) and then stabilised at 6.2% (4.6-7.8%) for the subsequent five months. FVC was similarly improved. Administration of rhDNase improved the severity of dyspnoea, cystic fibrosis related symptoms, and the modified Taussig/NIH score (not statistically significant). Fifty seven of the 59 patients completed the study; two died from progression of their pulmonary disease unrelated to treatment with rhDNase. The adverse events and intercurrent illnesses were no different from those expected in a cystic fibrosis population. Pharyngitis was the only possible drug related adverse event which occurred at least once in 14% of patients during the six month period. CONCLUSIONS: Administration of rhDNase was safe, well tolerated, and improved pulmonary function in patients with cystic fibrosis. When rhDNase was stopped at day 169 there was a deterioration in pulmonary function and dyspnoea score. PMID- 7785004 TI - Bronchial responsiveness and symptoms in 5-6 year old children: a comparison of a direct and indirect challenge. AB - BACKGROUND: The level of bronchial responsiveness in those with definite asthma correlates with disease severity and markers of airway inflammation. However, in population studies no clear distinction between normal and abnormal is found. Since the outcome of wheeze in early childhood is very variable, a marker of underlying airway inflammation would be of practical value. A stimulus acting indirectly may be more appropriate than one acting directly on smooth muscle. In this study the airway response to a direct (methacholine) and indirect (hypertonic saline) challenge have been compared in 5-6 year old children with past or present wheeze to see if symptom patterns or severity could be distinguished by either test. METHODS: Forty children with a wide spectrum of wheeze were monitored for a six month period after which their pattern and severity of symptoms were graded. Hypertonic saline and methacholine challenges were then performed on separate days. The response was assessed by both respiratory resistance (Rrs6) and transcutaneous oxygen (PTCO2). Atopic status was determined by IgE and skin prick tests. RESULTS: The results of both challenges were similar whether assessed by Rrs6 or PTCO2. There was no difference in the response to either methacholine or saline between different symptom patterns or severity grades, nor was there any correlation with either test to atopic status. CONCLUSIONS: Neither an indirect nor a direct challenge distinguished between past or present wheeze or degree of clinical severity in this group of children. Either wheezy children of this age do not have airway inflammation or bronchial responsiveness is not a marker for it. PMID- 7785005 TI - Analysis of tidal expiratory flow pattern in the assessment of histamine-induced bronchoconstriction. AB - BACKGROUND: There are times in clinical practice when it would be useful to be able to assess the severity of airways obstruction from tidal breathing. Three indices of airways obstruction derived from analysis of resting tidal expiratory flow have previously been described: (1) Tme/TE = time to reach maximum expiratory flow/expiratory time; (2) Krs = decay constant of exponential fitted to tidal expiratory flow versus time curve; and (3) EV = extrapolated volume- that is, area under the curve when the fitted exponential is extrapolated to zero flow. In this paper a further index--dtr/TE, time from the beginning of expiration till the rapid decay of flow begins/expiratory time--is evaluated. The aim of this study was to assess the ability of these indices to detect mild airways obstruction. METHODS: A histamine bronchial provocation test was performed in 20 adult patients with a diagnosis of asthma or symptoms of cough and/or shortness of breath. Baseline forced expiratory volume in one second (FEV1), functional residual capacity (FRC), and specific inspiratory conductance (sGaw) were measured and the measurements repeated after the final inhalation of histamine. Expiratory flow patterns during quiet breathing over five consecutive representative breaths were analysed before and after histamine. The test was concluded in 12 subjects when FEV1 had decreased by 20% of the post saline value, and in the remaining eight after inhalation of 16 or 32 mg/ml histamine. RESULTS: FEV1, sGaw, FRC, Krs, EV, and dtr/TE were all different after histamine (paired t test). For Tme/TE no difference was shown. Change in EV detected change in end tidal volume but underestimated it compared with the change measured by body plethysmography. Percentage fall in Krs after histamine correlated with percentage fall in FEV1 (r = 0.527, Pearson correlation coefficient). This was of a similar order to the correlation between the percentage fall in sGaw and in FEV1 (r = 0.543). CONCLUSIONS: Analysis of expiratory tidal flow-time patterns predicted a decrease in FEV1 following histamine challenge as did measurement of sGaw. This analysis of tidal breathing would be useful in circumstances where forced expiratory manoeuvres are unreliable or inapplicable. PMID- 7785008 TI - Expiratory muscle training and sensation of respiratory effort during exercise in normal subjects. AB - BACKGROUND: The sensation of respiratory effort may increase as expiratory muscles become fatigued during expiratory loading. A study was performed to determine whether expiratory muscle training (EMT) affects the sensation of respiratory effort during exercise in healthy subjects. METHODS: Six subjects performed EMT for 15 minutes twice daily for four weeks using a pressure threshold device; another six subjects served as a control group. The expiratory threshold was set at 30% of the individual's maximum expiratory mouth pressure (PEmax). The sensation of respiratory effort was evaluated during a progressive exercise test using the Borg scale. RESULTS: After EMT PEmax increased by 25% in the training group. The Borg score increased as exercise grade increased before and after EMT, but scores for each grade were lower after EMT. Minute ventilation during exercise decreased after EMT, as did the breathing frequency during exercise, while the expiratory time increased. Although there was no difference in the relationship between Borg score and minute ventilation before or after EMT, the curve shifted to a lower Borg score after EMT. There were no changes in PEmax, Borg score, minute ventilation, or breathing pattern after the four week study period in the control group. CONCLUSION: These findings suggest that EMT increases expiratory muscle strength and reduces the sensation of respiratory effort during exercise, presumably by reducing minute ventilation. PMID- 7785007 TI - Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid. AB - BACKGROUND: Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. METHODS: Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush. RESULTS: Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis. CONCLUSIONS: Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation. PMID- 7785009 TI - Maximal values of sniff nasal inspiratory pressure in healthy subjects. AB - BACKGROUND: Inspiratory muscle strength is often better reflected by oesophageal pressure during a maximal sniff (sniff POES) than by maximal inspiratory pressure (PImax). Sniff POES can be estimated non-invasively by measuring the sniff nasal inspiratory pressure (SNIP). The aim was to establish maximal normal values for the SNIP and to compare them with PImax. METHODS: One hundred and sixty healthy subjects (80 men) aged 20-80 years were recruited. All subjects had a forced vital capacity (FVC) of > 80%, a forced expiratory volume in one second (FEV1)/FVC of > 85% predicted value, and a body mass index of 18-31 kg/m2. Because PImax is known to be reduced in the supine posture, the SNIP was measured in both the sitting and the supine positions. PImax sustained over one second was measured from functional residual capacity (FRC) in the sitting position with a standard flanged mouthpiece during four manoeuvres. SNIP was measured from FRC in the sitting and supine positions using a catheter through a plug occluding one nostril during 10 maximal sniffs through the contralateral nostril. For each test the largest pressure measured in cm H2O was taken into account. RESULTS: For both men and women maximal SNIP was negatively correlated with age, and was similar in the sitting and the supine positions. In the sitting position maximal SNIP was greater or equal to PImax in 107 of 160 subjects. The mean (SD) ratio SNIP/PImax was 1.08 (0.22) in men and 1.17 (0.29) in women. CONCLUSIONS: Normal values of maximal SNIP can be predicted from age and sex. Maximal SNIP is similar in the sitting and the supine position and is significantly higher than PImax in healthy subjects. The low level of agreement between maximal SNIP and PImax indicates that the two manoeuvres are not interchangeable but complementary. PMID- 7785010 TI - Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) periods of hypopnoea occur during rapid eye movement (REM) sleep, but the mechanisms involved are not clear. METHODS: Ten patients with stable COPD were studied during nocturnal sleep. Detailed measurements were made of surface electromyographic (EMG) activity of several respiratory muscle groups and the accompanying chest wall motion using magnetometers. RESULTS: Hypopnoea occurred in association with eye movements during phasic rapid eye movement (pREM) sleep. During pREM sleep there were reductions in EMG activity of the intercostal, diaphragm, and upper airway muscles compared with non-REM sleep. Episodic hypopnoea due to partial upper airway occlusion ("obstructive" hypopnoea) was seen consistently in four subjects while the others showed the pattern of "central" hypopnoea accompanied by an overall reduction in inspiratory muscle activity. Although activity of the intercostal muscles was reduced relatively more than that of the diaphragm, lateral rib cage paradox (Hoover's sign) was less obvious during pREM-related hypopnoea than during wakefulness or non-REM sleep. CONCLUSIONS: Hypopnoea during REM sleep in patients with COPD is associated with reduced inspiratory muscle activity. The pattern of hypopnoea may be either "obstructive" or "central" and is generally consistent within an individual. Relatively unopposed action of the diaphragm on the rib cage during REM sleep is not accompanied by greater lateral inspiratory paradox. PMID- 7785006 TI - Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma. AB - BACKGROUND: Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS: The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS: A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS: These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma. PMID- 7785012 TI - Attenuation of ischaemia reperfusion injury by human thioredoxin. AB - BACKGROUND: Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS: Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS: In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS: These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals. PMID- 7785013 TI - Initial experience of video assisted thoracoscopic pneumonectomy. AB - BACKGROUND: Preliminary experience of video assisted thoracoscopic pneumonectomy in six patients with bronchogenic carcinoma is described. METHODS: Four left and two right pneumonectomies were performed under video thoracoscopic imaging. Thoracoscopic instruments were passed through two separate stab incisions on the lateral chest wall and a separate 6 cm submammary incision was also created to allow further access for instrumentation and removal of the resected lung. In this initial experience resection was restricted to patients with bronchogenic carcinomas of less than 6 cm in diameter who had no involvement of the mediastinum. RESULTS: There were no operative deaths and no complications attributable to the technique. One patient developed postoperative atrial fibrillation and a small sacral sore and one patient was readmitted with abdominal pain and pyrexia which settled following exclusion of post pneumonectomy empyema. The remaining four patients made a rapid uncomplicated postoperative recovery with less pain and discomfort than that normally associated with a standard posterolateral thoracotomy. Postoperatively the mean (SD) patient controlled morphine consumption was 1.36 (1.90) mg per hour in the first 36 hours compared with the unit mean for open thoracotomy of 1.73 (1.68) mg per hour. The mean linear visual analogue pain score was 15.4 (15.6) in the first 24 hours compared with the unit mean for open thoracotomy of 34.5 (8.5). CONCLUSIONS: Video assisted thoracoscopic pneumonectomy can be performed safely in patients who have stage I and stage II bronchogenic carcinomas, up to 6 cm in diameter, with no mediastinal involvement on mediastinoscopy and thoracic computed tomographic assessment. This technique may result in less postoperative pain and discomfort and should allow a quicker return to normal activities. PMID- 7785011 TI - Critical evaluation of computerised x ray planimetry for the measurement of lung volumes. AB - BACKGROUND: Computerised x-ray planimetry has been advocated as an alternative to body plethysmography and helium dilution for measuring static lung volumes. The accuracy and reproducibility of this method has been assessed in comparison with these standard methods. METHODS: Plethysmographic and planimetric measurements of total lung capacity (TLC) and functional residual capacity (FRC) were made in 10 normal subjects and in 12 patients with chronic obstructive pulmonary disease (COPD), with additional helium dilution measurements in the latter 12 patients. RESULTS: Mean lung volumes (TLC and FRC) for groups of subjects measured by planimetry and by plethysmography were similar in both groups and larger than the helium dilution measurement in patients with COPD. Intraindividual agreement between planimetry and plethysmography was poor, however, with a wide confidence interval (-2.2 to +2.31). The planimeter did not measure reliably changes in volume from TLC to FRC in individuals. CONCLUSIONS: Mean lung volumes measured by planimetry in a group of patients probably reflect a regression to the mean of the computer algorithm rather than accurate TLC estimation. The technique is not yet robust enough to replace the established techniques of helium dilution or plethysmography. PMID- 7785014 TI - Surgical management of pulmonary hydatid cysts in children. AB - BACKGROUND: Hydatid disease is common in Libya with a prevalence of 2%. Surgery of pulmonary hydatid disease remains the best treatment and aims to remove the cyst or its remnants and obliterate the residual cavity. METHODS: Forty three consecutive patients under 15 years of age were investigated by plain chest radiography, ultrasonography of the abdomen, and indirect haemagglutination tests. At thoracotomy the parasite or its remnants were removed and the bronchial fistula sutured. RESULTS: All but four of the patients were discharged within 12 days. These four had had their large cavities obliterated by purse string sutures and developed air fluid levels with cavity reformation at the cyst site. They were treated conservatively by physiotherapy and antibiotics and remained in hospital for 2-3 weeks. There was only one recurrence after three years of follow up. CONCLUSIONS: Pulmonary hydatid cysts in children can be treated successfully by evacuation and obliteration. The methods described can also be applied to adults. PMID- 7785015 TI - Acute lung injury in fulminant hepatic failure following paracetamol poisoning. AB - BACKGROUND: There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS: The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS: Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS: Acute lung injury was common in patients with paracetamol-induced fulminant hepatic failure and was associated with systemic circulatory failure and cerebral oedema. The development of acute lung injury was associated with high mortality. PMID- 7785016 TI - Compliance at night with low flow oxygen therapy: a comparison of nasal cannulae and Venturi face masks. AB - BACKGROUND: The factors that influence nocturnal compliance among patients prescribed low flow oxygen therapy were determined and tolerance of nasal cannulae and Venturi face masks compared. METHODS: Two studies were performed: (1) a prospective study of 99 hospitalised patients prescribed low flow oxygen therapy, 49 on nasal cannulae and 50 on Venturi face mask; and (2) a prospective study of 20 separate patients with an acute respiratory disorder requiring low flow oxygen therapy who were given nasal cannulae and Venturi face mask on successive nights in random order. RESULTS: In study 1, 49 patients dislodged their device at least once during the night. Those using Venturi face masks and those over 75 years of age had the most dislodgements. In study 2 patients also dislodged Venturi face masks more frequently (mean (SD) 2.0 (2.4)) than nasal cannulae (0.7 (1.4)). Most patients expressed a preference for nasal cannulae. CONCLUSIONS: Nocturnal tolerance of nasal cannulae is superior to Venturi face masks, and this factor should be considered when choosing the method of oxygen delivery. PMID- 7785017 TI - AIDS and the lung: update 1995. 3. Intrathoracic Kaposi's sarcoma in patients with AIDS. PMID- 7785019 TI - Fatal chickenpox pneumonia in an asthmatic patient on oral steroids and methotrexate. AB - A 49 year old man with a long history of severe chronic asthma, treated with oral corticosteroids and weekly doses of methotrexate, contracted chickenpox from his son whose chickenpox rash had developed three weeks before presentation. Five days before admission the patient developed a vesicular skin rash which became extensive, with general malaise, bilateral pneumonia, and acute deterioration of his asthma. He died two weeks after admission despite treatment with acyclovir. PMID- 7785020 TI - Bronchiectasis and homozygous (P1ZZ) alpha 1-antitrypsin deficiency in a young man. AB - Pulmonary complications of alpha 1-antitrypsin deficiency are most commonly manifested by panlobular emphysema. This report describes histologically proven bronchiectasis in a 21 year old man with massive haemoptysis and homozygous deficiency of alpha 1-antitrypsin. Neither panlobular emphysema nor cirrhosis of the liver were present. Bronchiectasis must be considered part of the spectrum of the pulmonary pathology that may be encountered in individuals with alpha 1 antitrypsin deficiency. PMID- 7785018 TI - New strategies for treatment of pulmonary fibrosis. PMID- 7785021 TI - Demonstration of supernumerary tracheal bronchus by computed tomographic scanning and magnetic resonance imaging. AB - A bronchus arising directly from the trachea is an infrequent congenital anomaly which usually represents the displaced origin of a normal bronchus. Rarely, a true supernumerary tracheal bronchus occurs supplying an associated tracheal lobe. The case is described of a patient in whom a supernumerary tracheal bronchus and tracheal lobe was demonstrated by computed tomographic scanning and magnetic resonance imaging. PMID- 7785022 TI - Replacement of one lung by a large bulla in active tuberculosis. PMID- 7785023 TI - Co-amoxiclav levels in bronchial mucosa. PMID- 7785025 TI - [While we are waiting for the Social Welfare Draft...the constitutional law on social insurance may be critically scrutinized]. PMID- 7785024 TI - Effects of ACE inhibition on sodium excretion in COPD. PMID- 7785026 TI - [Under the magnifying glass--treatment of stroke]. PMID- 7785027 TI - [Testicular cancer--Norway among the countries with the highest frequency. Regional multicenter cooperation is effective]. PMID- 7785029 TI - [Rehabilitation status at a regional social insurance office. Experiences with 103 clients at the Grunerlokka-Sofienberg office]. AB - 103 patients, mostly females, on rehabilitation measures mainly because of psychiatric conditions and chronic musculo-skeletal pain syndromes, were investigated with regard to outcome. In general, the patients had a low level of education, only 10% had vocational training, and most were unskilled labourers. Prior to the rehabilitation period they had been certified sick on several occasions. On average, the patients were followed up for three years. 84% were still on medical rehabilitation, i.e. they were under more or less systematic medical treatment, and were receiving benefits. 8% had been granted a disability pension, and only 4% had managed to become independent of the social insurance system. Until the recent years the rehabilitation system has functioned inefficiently as regards bringing people back to work. The patients remain inactive for long periods, owing to lack of planning and systematic implementation of rehabilitation measures, medical as well as vocational. In addition the vocational quality requirements of the labour market make it hard for people even with mainly minor health problems to obtain employment. PMID- 7785030 TI - [Ethical considerations in neonatal medicine]. AB - Ethical dilemmas are a daily occurrence in neonatal intensive care units. Some of these questions relate to life-and-death issues such as whom to treat or not to treat, if and when to discontinue life support, and organ donation. However, other issues are just as important in daily practice. These include the choice of a framework for ethical discussions, the question of who participates in the discussions, the parents' right to participation and information, the process and timing of decision-making, the ethics of clinical research in subjects unable to consent, respect and communication between health professionals, and the limits of confidentiality. In most of these dilemmas there is no quick and easy route to the one and only true answer. Neonatal health care workers are frequently confronted with ethical dilemmas, and are forced to reflect ethically. In this process, it is essential to be able to listen attentively to others, health workers as well as lay persons, and to integrate their opinions into one's own reflections. These two factors together must form the basis for daily clinical work and for ethical decisions. PMID- 7785031 TI - [Ventilator treatment at a subregional neonatal unit. Experiences form the Vestfold central hospital 1989-1994]. AB - During the six-year period 1989-94, 106 infants were treated with mechanical ventilation at the neonatal unit, Vestfold Central Hospital, Tonsberg, Norway (0.8% of live born infants). A total of 114 treatments were started. Indications were respiratory distress syndrome (RDS) in 63 (55%) of the treatments, asphyxia in 21 (18%), septicaemia/pneumonia in 12 (11%), congenital malformations in 8 (7%) and other indications in 10 (9%). 56 (49%) of the treatments lasted less than 24 hours until extubation or transportation to a regional hospital. The mean duration of treatment was 42.2 hours (range 0.7-183 hours). Pneumothorax occurred in seven infants (7%), in six of these during resuscitation and stabilizing treatment before mechanical ventilation. 16 infants (15%) died (cumulated mortality). Of the 90 surviving infants, nine (10%) acquired brain damage. The local ventilator treatment programme reduced the need of postnatal transports in infants with RDS by 65% during the period 1989-94 (1.2 per 1000 live born infants) compared with the period 1982-88 (3.4 per 1000) (p < 0.01). Ventilator treatment programmes for newborn infants can be undertaken safely at a subregional neonatal unit. The incidence of postnatal transports to a regional hospital is reduced. PMID- 7785028 TI - [Testicular cancer treated at the regional hospital in Tromso 1985-1993]. AB - The case histories of 98 patients (47 seminomas and 51 non-seminomas) treated at the Department of Oncology, University Hospital of Tromso between January 1985 and March 1993 were retrospectively analysed in August 1994. The analysis was undertaken to ascertain whether a small centre can achieve state of the art results. Complete remission was achieved in all cases. During a four year median follow-up period (range 1-10 years), three seminomas and eight non-seminomas relapsed. Only one retroperitoneally located relapse was revealed after retroperitoneal lymph node dissection. Two patients (one seminoma, one non seminoma) died of progressive disease. A statistically significant correlation was found between stage of disease and human chorionic gonadotropin, lactate dehydrogenate and alpha-fetoprotein in non-seminoma. Our results are similar to those of the major oncological centres. Hence our unit is able to achieve state of the art results in the treatment of testicular carcinomas. PMID- 7785033 TI - [Stroke. An effective evaluation and specialized treatment]. AB - Stroke is an acute disorder with a high fatality rate and with severe residual impairment among many of the survivors. Advances in neuroimaging and ultrasound have increased our understanding of the disease process. New drugs seem to reduce the neuronal damage caused by brain infarction if they are administered within the first few hours after onset of stroke. Management of stroke patients in a specialised stroke unit hastens recovery and is associated with a sustained reduction in mortality. Both recovery and survival can be jeopardized by cerebral, systemic, and cardiac complications, which may be attenuated by rigorous attention to general medical factors. Treatment of acute stroke will certainly change dramatically in coming years. PMID- 7785032 TI - [Combination of low molecular weight heparin and non-steroidal anti-inflammatory agents]. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) play an important part in postoperative relief of pain. Non-steroidal anti-inflammatory drugs and paracetamol should act as non-opioid basis analgesics in the postoperative period, leading to reduced need of opioid analgesia. This is beneficial, since it may reduce possible dosage-dependent side-effects of opioids such as nausea, tiredness and respiratory depression. The inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs also affects haemostasis, and the combination of these drugs with prophylaxis against postoperative thrombosis with heparin is controversial. We refer to a case history which illustrates this controversy. We also discuss the effect of non-steroidal anti-inflammatory drugs on pain and inflammation. Possible side-effects of these drugs and their interaction with heparin are reviewed. PMID- 7785034 TI - [Peripheral neuropathies]. AB - Some new aspects of peripheral nerve disease are reviewed. Hereditary motor and sensory neuropathy (HSMN) constitutes a genetically heterogeneous group of chronic polyneuropathies with loci mapping to chromosome 17 (type Ia), chromosome 1 (type Ib), and the X chromosome (X-linked HSMN). Although peripheral nerve abnormalities occur in approximately 50% of diabetic patients, the frequency of severe diabetic neuropathy even in insulin-dependent persons is rather modest (6%). Intensified insulin treatment seems more important for preserving peripheral nerve function than treatment with aldose reductase inhibitors. Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barre syndrome) and chronic inflammatory demyelinating polyneuropathy may both be beneficially influenced by plasma exchange or intravenous immunoglobulin. In acute inflammatory demyelinating polyradiculoneuropathy, campylobacter jejuni infection is a common preceding event. There is some evidence of cross reactivity between this infectious agent and the ganglioside GM1 in peripheral nerve myelin. PMID- 7785035 TI - [What do we know about the frequency of stroke? A review of incidence studies]. AB - In Norway, mortality from stroke has declined during the last 30-40 years. It is unknown whether the frequency of stroke has declined. This article presents studies on incidence and trends in incidence of stroke in different countries, especially Scandinavian countries. Geographical differences in incidence are small, when the rates are compared, adjusted for age and sex. Time trend studies on incidence give conflicting results. Some studies suggest increasing incidence of stroke, others a decrease or even no change of incidence. The age-standardised incidence rate (adjusted to the Norwegian population) from six studies in people aged 55-84 years is estimated to 6-8 per 1,000 per year. Little is known about incidence and time trend in Norway. Factors of importance for primary prevention of stroke (e.g. treatment of hypertension), treatment and rehabilitation of the stroke patient and knowledge about the incidence. PMID- 7785036 TI - [Rehabilitation of stroke patients--does it have an effect?]. AB - A search of the literature was carried out in order to identify controlled trials to study the effect of rehabilitation after a stroke. A limited number of studies have been published, and many are of poor quality. Making the organization of rehabilitation more efficient, emphasizing early start of rehabilitation, and close cooperation between the involved health professionals and an improvement of their competence have the best documented effect on mortality and on the percentage of patients who return home. There is also evidence that retraining of motor function and of language skills is effective. Rehabilitation seems to lead to more rapid recovery and a better result overtime. However, the achieved functional level may decline when the rehabilitational efforts are scaled down. The effect of rehabilitation on sensory and cognitive functioning is poorly documented. PMID- 7785039 TI - [A catalog of institutions for drug abuse treatment]. PMID- 7785037 TI - [Assessment by consulting physicians and general practitioners about complex disability pension matters]. AB - In the study we wanted to explore physicians' judgement of applicants for disability benefit who have complex medical and psychosocial histories. A postal questionnaire was used, containing six patient management problems focusing on whether the applicant would fill the criteria for obtaining a disability benefit according to Norwegian legislation. The participants were all medical officers hired as consultants by the social security officers in Norway (n = 122, response rate 75%) and a random sample of Norwegian general practitioners (n = 160, response rate 55%). There was a high degree of variation among physicians. The tendency to spread was almost parallel in the two groups of doctors, but the general practitioners tended to be slightly more liberal (in favour of disability benefit) than the social security medical officers. The latter expressed a more optimistic view of the rehabilitation potential of the applicants. Some physicians in each group seemed to be generally restrictive, others were liberal. Younger doctors seemed to be slightly more restrictive than older ones, while the attitudes of the physicians did not seem to be influenced by their sex, the form of payment or the location of the practice. The variation within each group of doctors indicates that both feedback and further discussion are needed to improve quality in this field of social security medicine. PMID- 7785038 TI - [What happens to patients not granted disability pension?]. AB - Subsequent to a recent (1991) narrowing of the medical legibility criteria for granting disability pensions in Norway, we wanted to follow up rejected applicants with regard to main sources of income. As setting were chosen five mainly rural municipalities on the North-West coast of Norway and the city of Trondheim. The study was carried out as a historic prospective study of a sample of rejected applicants for a disability pension, mainly based on follow-up data from local social security offices. Among a sample of 146 applicants rejected in 1990/91 and 1992, 143 (87 women and 56 men) were available for the analysis in March 1994. A rather stable 20% of the sample were occupationally active throughout three years of follow-up, this percentage being slightly higher among women than among men. In spite of the initial rejection, 25% had been granted a disability pension after two years. The rest received other kinds of public social support, or had left the labour market and had no social security support (mostly women). PMID- 7785040 TI - [An advertising campaign with adverse effects]. PMID- 7785041 TI - [Suture material and suturing of the laparotomy wound in horses and cattle]. AB - Wound healing is discussed in the introduction. Subsequently in a review of the suture materials used in large animal laparotomies is presented. In the discussion examples are given of the suture materials that are used at the Department of General and Large Animal Surgery. PMID- 7785043 TI - [Veterinary medicine after 2002, preliminary questions]. PMID- 7785042 TI - [A pig farm with chronic fertility problems]. AB - A herd with 320 sows with chronic fertility problems is described. About 20 to 30% of the inseminated sows returned to oestrus, for unknown reasons. When the interval from insemination to return to oestrus was analysed, it appeared that 20% of the sows returned between 24 and 28 days. A thorough and extensive control of the pig-farmer's oestrus detection technique revealed that nearly all sows were inseminated between 4 to 6 days post-weaning. However, this was too early for a number of sows. These sows showed optimal oestrus symptoms 6-8 days post weaning. This was also the explanation for the high number of sows returning to oestrus 'irregularly' between 24 and 28 days. Thus when analysing insemination intervals, the interval between 24 and 35 days should not be considered as one period but should be divided into the periods, 24-28 days and 29-35 days. In this way it is possible to distinguish between sows inseminated too early and sows returning to oestrus irregularly. PMID- 7785044 TI - [Veterinary medicine after 2002: the market]. PMID- 7785045 TI - [Bald back]. PMID- 7785046 TI - [Hepatic encephalopathy]. PMID- 7785047 TI - Chemical-induced vasculature injury. Summary of the symposium presented at the 32nd annual meeting of the Society of Toxicology, New Orleans, Louisiana, March 1993. AB - The cross-sectional structure of the vasculature is comparatively simple, comprising three layers--the intima, adjacent to the lumen, the media, and the adventitia. Notwithstanding this simplicity, the vessels are host to a variety of reactions to injury. Two cell types, endothelial cells of the intima and smooth muscle cells of the media, are principal targets of damage and repair. The endothelial cells of the intimal layer of the vessel wall present a macromolecular barrier and are important in maintaining vessel integrity. When the integrity is compromised by physical or chemical injury, endothelial cells play a key role in the repair processes. The use of single-cell wound models allows the mechanisms of damage and subsequent repair to be studied in depth. Repair processes can be observed using time-lapse photography and differences between cytoskeleton changes during repair and reendothelialization of small and large wounds can be discriminated. In rats treated with the plant toxin monocrotaline, pulmonary vascular injury occurs which manifests as thrombosis and remodeling with consequent progressive pulmonary hypertension. In vivo and in vitro studies of the mechanism of monocrotaline toxicity suggest that the endothelial cells are an important target. In vitro studies show monocrotaline to be directly cytotoxic; in cells that survive, there are functional changes to the endothelial cells, resulting in a decreased repair capability which may lead to the complex, progressive lung lesions that develop. The other target cells of the vasculature are the smooth muscle cells of the media. Ingestion of primary amines allylamine and beta-aminopropionitrile (beta-APN) results in chronic vasculotoxicity to the aorta and medium-sized arteries. For allylamine, subtle changes in smooth muscle result in medial hypertrophy and subintimal proliferation. The changes are slow to occur, taking weeks or months of repeated treatment. For beta-APN, which is the active ingredient of the toxic sweet pea Lathyrus odoratous, vascular toxicity is manifested by fatal rupture of aortic aneurysms. When these agents are administered concomitantly, a synergistic acute smooth muscle necrosis occurs in large elastic arteries and degenerative changes are seen in muscular arteries. A change in the target for toxicity of allylamine toward the vasculature may be responsible for this synergistic toxic insult. Medial smooth muscle necrosis is also noteworthy after administration of certain pharmaceutical agents of diverse structure and pharmacological activity. These agents induce arteriopathies in dogs and rats, although at different sites. In dogs, the coronary arteries are susceptible, whereas in rats the mesenteric arteries are the principal sites of injury.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7785049 TI - Sex differences in hexachlorobutadiene biotransformation and nephrotoxicity. AB - Hexachlorobutadiene is nephrotoxic in rats, causing damage to the proximale tubules. Renal toxicity is presumed to be due to bioactivation by glutathione S conjugate formation. Hexachlorobutadiene is conjugated with glutathione to S (1,2,3,4,4-pentachlorobutadienyl)glutathione and further transformed to S (1,2,3,4,4-pentachlorobutadienyl)-L-cysteine (PCBC), which is N-acetylated in the liver to form N-acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine (N-ac PCBC). N-ac-PCBC is accumulated in the kidney. Renal acylases cleave N-ac-PCBC to PCBC, which is a substrate for renal cysteine conjugate beta-lyase and transformed to a reactive thioketene. Binding of this intermediate to renal macromolecules is most likely responsible for the nephrotoxicity of hexachlorobutadiene. In this study, we administered [14C]HCBD (200 mg/kg, per gavage) to male and female Wistar rats and compared the distribution and biotransformation. No significant differences in the disposition and rates of excretion of [14C]hexachlorobutadiene-derived radioactivity were observed between male and female rats. A portion of the dose (15.6 +/- 4.2) was excreted in the feces and 3.1% ( +/- 0.7) in the urine of male rats, and 11.1% ( +/- 3.8) of the dose was excreted in the feces and 4.5% ( +/- 1.5) in the urine of female rats. The major metabolite excreted by female rats was N-ac-PCBC, while small amounts of PCBC were also detected. In the urine of male rats, in addition to small amounts of PCBC and N-ac-PCBC, N-acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L cysteine sulfoxide and [14C]hexachlorobutadiene were identified. Formation of the electrophile N-ac-PCBC sulfoxide must be considered as an alternative, beta-lyase independent, bioactivation pathway for hexachlorobutadiene-derived S-conjugates. In isolated rat renal tubular cells, N-ac-PCBC sulfoxide induced a significantly more marked loss in cell viability than N-ac-PCBC. After identical doses of hexachlorobutadiene, the extent of necrosis to the pars recta of the proximal tubules was increased in male rats compared to the necrotic changes in female rats. While female animals showed a normal liver histology, male rats revealed slight toxic centrilobular liver changes in addition to the renal necroses. In vitro, only liver microsomes from male rats catalyzed the formation of N-ac-PCBC sulfoxide from N-ac-PCBC. Our results describe a new pathway of hexachlorobutadiene biotransformation in male rats, the formation of a mercapturic acid sulfoxide. The formation of this Michael acceptor may contribute to sex differences in hexachlorobutadiene nephrotoxicity. PMID- 7785048 TI - MK-801 protects against carbon monoxide-induced hearing loss. AB - MK-801, a glutamate receptor blocker, has been reported to protect against hypoxic-ischemic neuronal degeneration. The purpose of this study was to investigate the protective effects of MK-801 on cochlear impairment induced by carbon monoxide (CO) in the guinea pig and whether the protection reflected systemic or local effects. Glutamate has been proposed to be the neurotransmitter at the inner hair cell/type I spiral ganglion cell synapse. CO (35 ml/kg ip) elevated the compound action potential threshold at high frequencies (16-40 kHz) 30 min after treatment. In the group pretreated with 1 mg/kg MK-801 ip there was no significant elevation of compound action potential threshold 30 min after CO exposure, suggesting that MK-801 provided some protection at this dosage. In the group pretreated with 0.1 mg/kg MK-801 there was protection against cochlear dysfunction 15 min after CO injection, but significant elevation of compound action potential threshold occurred 30 and 60 min after CO exposure. Data also indicated that 1 mM MK-801 applied topically on the round window membrane provided protective effects against CO hypoxia from 15 up to 60 min. This experiment suggests that cochlear impairment induced by CO hypoxia may result from excess extracellular concentrations of glutamate. PMID- 7785051 TI - Transforming growth factor beta 1 preferentially induces apoptotic cell death in rat hepatocytes cultured under pericentral-equivalent conditions. AB - The cytotoxicity of transforming growth factor beta 1 (TGF beta 1) was assessed in rat hepatocytes cultured under periportal (PP)-or pericentral (PC)-equivalent conditions. TGF beta 1 induced a 5-fold greater DNA fragmentation and LDH release in PC cultures than in PP cultures. At low exposure level (1 ng/ml TGF beta 1), albumin secretion and mitochondrial activity (rhodamine-123 uptake) were selectively reduced in PP cultures, whereas the incidence of apoptotic cells in PC cultures was about 10-fold higher than that in PP cultures. The time profiles of TGF beta 1-induced apoptotic and necrotic events and the concentration response relationship differed in PC and PP cultures. In PC cultures the early appearance of cells with apoptotic nuclei was not associated with DNA fragmentation nor with an increase in LDH release or impaired mitochondrial function. At a high exposure level (5 ng/ml TGF beta 1), again cells with apoptotic nuclei were much more strongly induced in PC cultures but DNA fragmentation, LDH release, and impairment of mitochondrial activity all increased in an exposure-time dependent manner in both PP and PC cultures. At this exposure level 48 and 72% of the apoptotic cells detected in PC cultures after continuous exposure for 24 hr were induced within an exposure of 1 and 4 hr, respectively. Aurintricarboxylic acid (50 microM), an inhibitor of endonucleases, significantly inhibited the appearance of apoptotic cells and the progression in apoptosis. Clearly, TGF beta 1 preferentially induced apoptotic cell death in hepatocytes with PC-equivalent metabolism at low exposure levels. High exposure levels or prolonged exposure periods produced both apoptosis and necrosis. PMID- 7785050 TI - The hematotoxic effects of 6-hydroxy-trans,trans-2,4-hexadienal, a reactive metabolite of trans,trans-muconaldehyde, in CD-1 mice. AB - 6-Hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH) is a metabolite of trans,trans muconaldehyde (muconaldehyde or MUC), a microsomal hematotoxic ring-opened metabolite of benzene. In the present study, the toxicity of CHO-M-OH was examined. In order to assess potential toxic effects of CHO-M-OH on the maturation of erythroid cells in the bone marrow, 10-week-old male CD-1 mice were administered CHO-M-OH intraperitoneally and 59Fe incorporation into erythrocytes was measured. The uptake of 59Fe by erythroid cells was significantly inhibited at doses of 20, 25, and 30 mg/kg. There was no inhibition of 59Fe incorporation at a dose of 15 mg/kg. In other hematotoxicity studies, bone marrow cellularity, peripheral blood cells, and sulfhydryl contents in bone marrow cells were examined in mice administered CHO-M-OH intraperitoneally. An increase in the white blood cell count was observed in mice treated with 5 mg/kg/day for 16 consecutive days, while bone marrow cellularity and red blood cell parameters were not changed. Administration of 10 mg/kg/day for 16 consecutive days caused a significant decrease in sulfhydryls of bone marrow cells but no changes in bone marrow cellularity and peripheral blood parameters compared with controls. At a dose of 25 mg/kg/day for 4 days, there was a significant decrease in nucleated bone marrow cells. The white blood cell count, mainly lymphocytes, also significantly decreased. Our results indicate that CHO-M-OH is a hematotoxin in mice and conceivably could play a role in benzene toxicity. PMID- 7785052 TI - Differential toxicity of cisplatin, carboplatin, and CI-973 correlates with cellular platinum levels in rat renal cortical slices. AB - The differential toxicity of the platinum-containing compounds, cisplatin, carboplatin, CI-973, and transplatin, was investigated in renal cortical slices over a 24-hr period. Platinum accumulation was measured to assess whether platinum levels correlated with inhibition of specific cell functions (accumulation of organic ions, protein synthesis) or potassium loss. The earliest indicator of toxicity was decreased accumulation of the organic anion, para aminohippuric acid (PAH), which preceded a decrease in the accumulation of the organic cation, tetraethyl-ammonium (TEA), and protein synthesis. Cisplatin (1 mM) and CI-973 (3 mM) treatment reduced PAH accumulation within 2 hr; carboplatin (3 mM) decreased PAH at 6 hr. TEA accumulation was absent in slices incubated for 6 hr or longer in 1 mM cisplatin, or for 24 hr in 3 mM carboplatin or CI-973. Protein synthesis was inhibited 80, 75, and 87% in slices treated for 24 hr with 100 microM cisplatin, 1 mM carboplatin, and 1 mM CI-973, respectively, compared to control. Intracellular potassium levels, which decreased between 6 and 24 hr, were the least sensitive indicator of cell damage. Transplatin, which lacks antitumor activity and is nonnephrotoxic in vivo, effectively decreased protein synthesis, intracellular potassium, and organic ion accumulation in rat renal cortical slices in vitro. The concentration of slice-associated platinum following treatment with cisplatin, carboplatin, CI-973, and transplatin increased with time and concentration. Inhibition of protein synthesis and loss of intracellular potassium correlated with increased total cellular platinum, indicating that platinum compounds negatively affect cell function and viability. The relative toxicity of these compounds in rat renal cortical slices was cisplatin = transplatin > CI-973 > carboplatin. PMID- 7785054 TI - Regeneration of renal proximal tubule cells in primary culture following toxicant injury: response to growth factors. AB - Growth factors may play an important role in the repair of the renal proximal tubule epithelium following toxic injury. This study investigated the regeneration of rabbit renal proximal tubule cell (RPTC) monolayers following exposure to the nephrotoxicants tert-butylhydroperoxide (TBHP) and 1,2 dichlorovinyl-L-cysteine (DCVC), and the effect of exogenous growth factors on the regeneration process. Confluent monolayers exposed to TBHP or DCVC for 1.5-2 hr were 23 and 43% confluent, respectively, after 24 hr. Confluency increased to 63 and 80% 4 days after TBHP or DCVC exposure, but decreased to 29 and 24% after 8 days. Monolayer DNA content did not increase after TBHP or DCVC exposure; however, monolayer protein/DNA ratio increased above control values after DCVC exposure. Recovery of confluency was not sensitive to RGD-containing peptides that inhibit the binding of integrins to extracellular matrix. Epidermal growth factor (EGF) treatment resulted in complete recovery of confluency, and protein and DNA contents 4-6 days after injury. Unlike EGF, IGF-1 or insulin treatment produced a small increase in confluency following TBHP exposure. These results suggest that hypertrophy following DCVC exposure and migration/spreading after TBHP and DCVC exposure play a partial and temporary role in the regeneration of RPTC monolayers, that in the absence of exogenous growth factors proliferation and complete regeneration of the monolayer does not occur, that toxicants may alter the production of mitogenic factors, and that EGF is a potent and efficacious growth factor in promoting regeneration. PMID- 7785053 TI - TCDD reduces rat hepatic epidermal growth factor receptor: comparison of binding, immunodetection, and autophosphorylation. AB - Administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent tumor promoter, to rats resulted in a dose-dependent decrease in hepatic plasma membrane epidermal growth factor receptor (EGFR). The present study is the first to quantify and compare alterations in hepatic EGFR levels in female Sprague Dawley rats 7 days after a single oral gavage dose of TCDD (0, 1, 5, 25, and 50 micrograms/kg) using three different techniques: (1) equilibrium receptor binding, (2) EGF induced receptor autophosphorylation, and (3) Western blot detection with a rabbit anti-rat EGFR polyclonal antibody. All three methods similarly demonstrated that the level of hepatic EGFR is significantly decreased at a dose of TCDD as low as 1 micrograms/kg. We showed that the immunoblot technique is a sensitive and quantitative alternative to radioligand binding assays. It is concluded that TCDD decreased total EGFR protein and maximum binding capacity without altering ligand binding affinity (Kd). The results demonstrated that ligand-induced autophosphorylation capacity and basal phosphotyrosine residues of plasma membrane EGFR were both decreased parallel with the decrease in EGFR protein, suggesting no TCDD-related alteration in the inherent functional ability of the receptor to undergo activation. Furthermore, it was found that the dose-response curve for EGFR protein level determined by Western blot analysis was similar for both male and female Sprague-Dawley rats. PMID- 7785055 TI - High concentrations of butadiene epoxides in livers and lungs of mice compared to rats exposed to 1,3-butadiene. AB - 1,3-Butadiene (BD) is carcinogenic in B6C3F1 mice and Sprague-Dawley rats, and mice are more sensitive than rats. This study measured the concentrations of the putative DNA-reactive BD metabolites, butadiene monoxide (BMO) and butadiene diepoxide (BDE), in lung and liver of male Sprague-Dawley rats and B6C3F1 mice exposed to BD by inhalation. Samples (n = 3-6) of lung and liver were collected at 3 and 6 hr during and at 6 and 12 min following 6-hr nose-only inhalation exposure to 0, 62.5, 625, 1250, or 8000 (rats only) ppm BD. BMO and BDE were extracted into methylene chloride and quantified by gas chromatography-mass spectrometry. Since BD epoxides can be conjugated with glutathione (GSH), the nonprotein sulfhydryl content of lung and liver was quantified colorimetrically. Analytical limitations precluded quantitation of BD epoxides in tissues of rats or mice exposed to 62.5 ppm BD. Exposures greater than or equal to 625 ppm BD resulted in higher BMO concentrations in lungs and livers of mice compared to rats. In mice exposed to 625 and 1250 ppm BD, the maximum concentrations of BMO at 3 or 6 hr of exposure in lungs (2.6 +/- 0.2 and 3.7 +/- 1.2 nmol/g tissue; mean +/- SE) were higher than in livers (0.58 +/- 0.12 and 0.93 +/- 0.19 nmol/g). Rats exposed to 625 and 1250 ppm BD had lower concentrations of BMO in lungs (0.16 +/- 0.03 and 0.31 +/- 0.07 nmol/g) and livers (0.06 +/- 0.01 and 0.16 +/- 0.06 nmol/g) than mice. In rats exposed to 8000 ppm BD, the maximum concentrations of BMO in lungs (1.3 +/- 0.2 nmol/g) and livers (1.2 +/- 0.1 nmol/g) were nearly identical. BDE was quantified in lungs, but not livers, of mice exposed to 625 and 1250 ppm BD. The maximum concentrations of BDE in mouse lungs were 0.71 +/- 0.06 and 1.5 +/- 0.1 nmol/g, respectively; BDE was not detected in livers or lungs of rats exposed to any of the concentrations of BD tested. GSH depletion was dependent on the concentration and duration of BD exposure. The lungs of mice sustained the greatest magnitude of depletion (26% of control at 6 hr of exposure to 1250 ppm BD).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7785056 TI - Organic anion transport and action of gamma-glutamyl transpeptidase in kidney linked mechanistically to renal tubular uptake of inorganic mercury. AB - In the present study, the roles of renal tubular gamma-glutamyl transpeptidase and renal organic anion transport on the renal uptake and accumulation and intrarenal distribution of injected inorganic mercury were investigated. The renal (and general) disposition of injected inorganic mercury (Hg2+) was evaluated in control rats, rats pretreated with two 10 mg/kg doses of acivicin, rats pretreated with a 10 mmol/kg dose of p-aminohippurate (PAH), and rats pretreated with both acivicin and PAH. The dose(s) of acivicin were used to inhibit the activity of renal gamma-glutamyl transpeptidase to a near maximal level and the dose of PAH (which is a water-soluble organic anion) was used to competitively inhibit the renal organic anion transport system to a near maximal level. Dispositional data were obtained at both 1 and 24 hr after a nontoxic, 0.5 mumol/kg iv dose of mercuric chloride had been administered. Radiolabeled inorganic mercury (203Hg2+) was added to the injection solution containing the mercuric chloride to make it possible to quantitate the accumulation and disposition of mercury using standard isotopic methods. The renal concentration and content of mercury were significantly lower in the rats pretreated with either acivicin or PAH than in the control rats at both times after the injection of inorganic mercury. Pretreatment with acivicin mainly affected the content of mercury in the renal cortex, while pretreatment with PAH affected the content of mercury in both the renal cortex and the outer stripe of the outer medulla. Interestingly, the renal concentration and content of mercury in the rats pretreated with both acivicin and PAH were significantly lower than in any of the other three groups at both times after injection of inorganic mercury. Evaluation of the intrarenal distribution of mercury indicated that the renal cortex was the main zone in which the uptake of mercury was significantly affected by both acivicin and PAH. The findings from this study indicate that the renal tubular uptake of administered inorganic mercury is linked both to the transport of organic anions and to the action of gamma-glutamyltransferase. Thus, at least two mechanisms appear to be involved in the renal tubular uptake of inorganic mercury. PMID- 7785057 TI - Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice: dose-response studies. AB - Six groups of genetically mercury-susceptible female SJL/N (H-2s) mice were exposed to mercury vapor at a concentration of 0.3-1.0 mg Hg/m3 air for 0.5-19 hr/day 5 days a week for 10 weeks. The absorbed doses were calculated to be between 75 and 2365 micrograms Hg/week/kg body wt (micrograms Hg/week/kg). The correlation between the dose and the concentration of Hg in kidney, spleen, and thymus was highly significant (p < 0.0001; Spearman's rank correlation test). The lowest observed adverse effect level (LOAEL) for serum IgG antinucleolar antibodies (ANoA) was 170 micrograms Hg/week/kg, corresponding to a renal mercury concentration of 4.0 +/- 0.76 micrograms Hg/g wet wt. The correlation between the absorbed dose and the ANoA titer was highly significant (p < 0.0001; Spearman's rank correlation test), and all mice were ANoA-positive at a dose of 480 micrograms Hg/week/kg. High-titer ANoA targeted the nucleolar 34-kDa protein fibrillarin. The LOAEL for B-cell stimulation, measured as an increase in serum IgG2a and IgG1 concentrations, was 360 micrograms Hg/week/kg, but the increase was fivefold higher and also included IgE at a dose of 690 and 2365 micrograms Hg/week/kg. The serum Ig concentrations peaked after 2-4 weeks and then slowly declined but, except for IgE, remained significantly increased during the entire exposure time. Glomerular, mesangial IgG immune complex (IC) deposits, accompanied by systemic vessel wall IC deposits, were first detected at a dose of 480 micrograms Hg/week/kg. The mesangium also showed increased titers of IgM IC deposits and complement factor C3c. The correlation between the absorbed dose, and the individual titer of IgG, IgM, and C3c, was highly significant (p < 0.0001; Spearman's rank correlation test). In conclusion, mercury vapor efficiently induced an autoimmune syndrome in genetically susceptible mice, and the LOAEL for the adverse effects varied in the order ANoA < B-cell stimulation < IC deposits. Comparing the body burden of mercury in mice at the LOAEL for autoantibodies with the body burden in populations of occupationally exposed humans suggests that the safety margin may be narrow for genetically susceptible individuals. PMID- 7785058 TI - Validation of an in vitro teratology system using chiral substances: stereoselective teratogenicity of 4-yn-valproic acid in cultured mouse embryos. AB - In vitro systems are important for toxicity testing as well as for investigating the mechanism of action of xenobiotics. The validation of such in vitro systems is often incomplete and extrapolation to the in vivo situation is equivocal. In the present study, we studied the effects of enantiomers of an analogue of the antiepileptic drug valproic acid (VPA): R(+)- and S(-)-4-yn-VPA (R- and S-2-n propyl-4-pentynoic acid), which have previously been shown to induce selective teratogenicity in mice after in vivo administration, in mouse whole-embryo culture (WEC). Aqueous solutions of the sodium salts of the pure R- and S enantiomers as well as R,S-4-yn-VPA (racemic mixture) or VPA itself were added to the culture medium at 0, 0.075, 0.15, 0.3, 0.6, or 1.2 mmol/liter and embryos were evaluated 24 hr later. The S-4-yn-VPA enantiomer induced clear concentration dependent dysmorphogenesis that was evident even at the lowest concentration. The primary anomalies were neural tube defects, erratic neural seams, blisters, and rotational defects. Embryolethality was observed at 1.2 mmol/liter. The R-4-yn VPA enantiomer was neither embryotoxic nor dysmorphogenic at any tested concentration. The lack of biological activity over 24 hr in WEC with the R enantiomer suggests also that, as previously shown in vivo, there was no racemization of this isomer to the more active S-enantiomer. The racemic mixture of R and S isomers appeared to be slightly more embryolethal and dysmorphogenic than VPA. Overall, the potency of the S-enantiomer was approximately four times that of VPA. Therefore, the rank order of the four chemicals tested was S(-) >> S(-), R(+) > VPA >>> R(+), which is in agreement with the effects observed in in vivo exposed mice. These data demonstrate a direct stereoselective effect of these compounds on the embryo. This is the first illustration of the stereoselectivity of a xenobiotic in the WEC in vitro test system. Pure and stable enantiomers, which induce stereoselective toxicity in vivo, are demonstrated to be valuable for validation of this in vitro system. PMID- 7785059 TI - Peroxisome proliferator-activated receptor response specificities as defined in yeast and mammalian cell transcription assays. AB - Peroxisome proliferators include a heterogeneous group of xenobiotic agents capable of inducing peroxisome proliferation and hepatocellular carcinomas in rodent model systems. These chemicals appear to mediate their activity through a family of transcription factors known as peroxisome proliferator-activated receptors (PPAR). Recently it has been shown that DNA binding of PPAR is contingent upon heterodimerization with a member of the retinoic acid X (RXR) family of receptors. In this report transcription parameters of a rat PPAR alpha were analyzed using mammalian and yeast cotransfection assays. PPAR activity was observed to be peroxisome proliferator dependent in the mammalian cotransfection assay, and heterodimer dependent but peroxisome proliferator independent in a yeast version of the same assay. Moreover, when the naturally occurring ligand for RXR, 9-cis-retinoic acid (RA), was tested in the same assays, it was observed to generate an RXR-specific response in the yeast cell assay but host cell specific response in the mammalian cell assay. Finally, the combination of peroxisome proliferator and 9-cis-RA had very little added effect on the yeast cell assay but again produced a cell-specific synergistic response in the mammalian cell assay. These data demonstrate that PPAR transcriptional activity is strongly influenced by the RXR family of receptors, and that peroxisome proliferators may be regulating PPAR mammalian cell activity through a secondary mechanism. PMID- 7785060 TI - Autometallographic determination of inorganic mercury distribution in the cortex of the calcarine sulcus of the monkey Macaca fascicularis following long-term subclinical exposure to methylmercury and mercuric chloride. AB - The distribution of accumulated inorganic mercury deposits 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 determined by autometallography. Four groups of monkeys were exposed to MeHg (50 micrograms Hg/kg body wt/day) by mouth for 6, 12, and 18 months or 12 months followed by 6 months without exposure (clearance group). A fifth group of monkeys was administered inorganic mercury (as HgCl2; 200 micrograms Hg/kg body wt/day) for 3 months by constant rate intravenous infusion via an indwelling catheter. Staining of IHg deposits in the MeHg-exposed groups increased for all cell types with increased length of exposure. The astrocytes and microglia in the MeHg exposure groups contained the largest deposits of IHg. Neurons in the 6-month MeHg exposure group were either not labeled or contained very fine deposits of IHg. The frequency of labeled neurons increased somewhat in the 12-month and clearance exposure groups. Virtually all neurons in the 18-month exposure group contained labeled deposits of IHg; however, these total deposits were considerably smaller than those present within the astrocytes and microglia. The majority of endothelial cells and pericytes did not contain notable mercury deposits, although scattered individual cells were heavily labeled. Labeled oligodendrocytes were relatively rare in all MeHg-exposed groups. Gitter cells, primarily located in a perivascular position, were common in the 12-month, 18 month, and clearance groups and many of these were found to be heavily labeled. The staining of mercury deposits in the IHg-exposed animals was low compared to the MeHg-exposed groups. The astrocytes and microglia were the primary cell types labeled. It is concluded that the astrocytes, and possibly microglia, are the primary location of the demethylation of MeHg into IHg within the cortex of the calcarine sulcus. PMID- 7785061 TI - Relative potencies of induction of hepatic drug-metabolizing enzyme genes by individual PCB congeners. AB - The induction of a variety of drug-metabolizing enzymes by polychlorinated biphenyl (PCB) congeners that elicit a 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD)-type hepatic pleiotropic response, including 2,3,3',4,4' pentachlorobiphenyl (BZ 105), 2,3',4,4',5-pentachlorobiphenyl (BZ 118), 2,3,3',4,4',5-hexachlorobiphenyl (BZ 156), and 3,3',4,4',5,5'-hexachlorobiphenyl (BZ 169) was examined. Following dietary exposure to the individual congeners for 5 days, livers were removed and catalytic assays for cytochrome P450 (CYP) isozymes 1A1 and 1A2 were performed. Additionally, total cellular RNA coding for hepatic drug-metabolizing genes (CYP 1A1, CYP 1A2, microsomal epoxide hydrolase, glutathione S-transferase [GST] Ya/Yc, and the TCDD-inducible isozyme of aldehyde dehydrogenase [ALDH] was quantified. 3-Methylcholanthrene (MC), TCDD, or BZ 156 (32 ppm) caused nearly maximal induction of the CYP 1A proteins but lower induction of the other genes. When the dose-response curves for induction of various drug-metabolizing genes (CYP 1A1 and 1A2, microsomal epoxide hydrolase, the GST Ya/Yc subfamily and ALDH) were examined, a spectrum of ED50s (half maximal inductions) was observed. While CYP 1A2 exhibited an ED50 of 1.7 ppm, the induction of ALDH was shifted far to the right (ED50 > 11 ppm). Thus, different genes in a single tissue may display different dose-response characteristics. The potency (extent of induction of CYP 1A1 activity resulting from a given dietary dose) was BZ 169 >> BZ 156 > BZ 118 > BZ 105. In contrast, the potencies of the four congeners for CYP 1A1 induction were nearly equivalent when related to hepatic PCB burden, apparently due to the preferential accumulation in the liver of BZs 169 and 156 following low-level administration in the diet. PMID- 7785062 TI - Protective effect of various antagonists of inflammatory mediators against paraoxon-induced pulmonary edema in the rabbit. AB - The protective effect of some antagonists of various inflammatory mediators against paraoxon-induced increases in endothelial permeability has been investigated in isolated perfused rabbit lungs. The edema induced by paraoxon has been previously related to a chain reaction mediated by acetylcholine. Lungs were ventilated and blood-free perfused with a constant flow. Arterial and venous pressures and lung weight were continuously recorded. Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). Paraoxon (4 x 10(-4) M) was injected in the perfusion circuit, in lungs with or without pretreatment with atropine, ketanserin, clonidine, morphine, indomethacin, and terfenadine plus cimetidine. Paraoxon induced a time-dependent increase in the Kf,c, a maximal effect being recorded 60 min after the injection. All the antagonists used as pretreatment significantly reduced the maximal effect recorded after paraoxon. These results show that muscarinic receptor antagonists, inhibitors of neuropeptides release, cyclooxygenase inhibitors, and 5 hydroxytryptamine and histamine receptor antagonists can protect the lung against the edema induced by paraoxon. This protective effect is due to inhibition of the chain reaction triggered by acetylcholine. PMID- 7785063 TI - Diffusion of the culture of contraception: program effects on young women in rural Bangladesh. AB - This article describes a process of diffusion of family planning information, ideas, and technology among an unanticipated audience of young, unmarried women in rural Bangladesh. The data are derived from a focus-group study conducted in 1987-88 in the Maternal Child Health and Family Planning Project in Matlab, Bangladesh. A discussion with a staff member revealed her vivid memory of the arrival of the community-based family planning worker in her village 10 years earlier, before she was married. Based on this research lead, four focus-group sessions were held with newly married young women, and a set of questions about young women were incorporated into the sessions with other community women. The discussions showed that many young, unmarried women learn about family planning from an early age from the community-based family planning worker, from female relatives, peers, and the media. The findings of this exploratory study suggest that greater attention be paid to the contraceptive needs of young women and that continued research be conducted with this population of women. PMID- 7785065 TI - Beliefs and practices regarding delivery and postpartum maternal morbidity in rural Bangladesh. AB - Most maternal deaths occur in the puerperium and most maternal morbidities probably also arise at that time. Maternal morbidities occur much more frequently than maternal deaths, but very little is known about their magnitude or causes. This study uses focus-group discussions to explore the experiences of childbirth and postpartum illness among rural Bangladeshi women. The women's beliefs about disease causation, and their use of traditional health care, are explored. The significance of the findings for the training of traditional birth attendants and for programs of postpartum care is discussed. PMID- 7785064 TI - Comparing women's reports with medical diagnoses of reproductive morbidity conditions in rural Egypt. AB - This article is based on a survey of a random sample of 509 ever-married nonpregnant women residing in two villages in the Giza Governorate of Egypt, each of whom responded to a questionnaire on symptoms of gynecological conditions and then was accompanied to the village health center for a gynecological exam. A response rate of 91 percent was achieved. The article focuses on reproductive tract infections and genital prolapse, highly prevalent conditions in the community. The women's reports of symptoms are compared with the medical diagnoses, using indicators of sensitivity, specificity, positive and negative predictive values, and percentage of agreement. The findings show that women's reports of vaginal discharge agree moderately well with the physicians' observations but are not good predictors of the occurrence of reproductive tract infections. Women's reports of the symptoms of prolapse do not agree well with medical diagnoses of the condition. The findings are analyzed, taking into account the social context of the lives of the women surveyed to arrive at conclusions as to how to improve ways of learning from women themselves about gynecological problems in the community. PMID- 7785067 TI - Sterilization regret in the Dominican Republic: looking for quality-of-care issues. AB - This report approaches the concept of quality of care by looking at the covariates of sterilization regret in the Dominican Republic according to the results from the 1991 Demographic and Health Survey. The main variables observed are the women's satisfaction with sterilization, their decisionmaking process, sterilization experience, use of family planning, and socioeconomic characteristics. The more detailed measurement and analysis of the outcomes of care point to a need for improvement in the public program effort with regard to sterilization. Substantial proportions of women were sterilized who were younger than 30, who had three or fewer living children, and who had the operation before they had used any other method of contraception. Because a greater proportion of sterilization regret is observed among these groups, women must be enabled to make a free and informed decision about sterilization by means of programs that offer a more balanced choice of methods, as well as better counseling, education, and access to high-quality services. PMID- 7785068 TI - Philippines 1993: results from the National Demographic Survey. PMID- 7785066 TI - Maternal mortality estimation: separating pregnancy-related and non-pregnancy related risks. AB - The increased availability of survey data and improved estimation techniques have furthered our understanding of maternal mortality in developing countries. Both the indirect and direct sisterhood methods of estimation depend on time-of-death information from surveys. This report proposes a method for calculating two rates, one during the pregnancy period and one outside of it. Analysis of both rates provides more information about mortality associated with pregnancy than do methods that only produce one rate. The pregnancy-related mortality rate can be estimated by assuming that non-pregnancy-related risks are constant, irrespective of whether women are pregnant or not. An estimated 69 percent of deaths in Bolivia during pregnancy may be pregnancy related; this result is significantly lower than that obtained using the traditional sisterhood method. In certain cases, this result may be viewed as a plausible lower bound. A variety of estimates should probably be used for policy purposes. PMID- 7785069 TI - New bedfellows in the mammalian sex-determination affair. PMID- 7785070 TI - Gene therapy by and for muscle cells. PMID- 7785071 TI - Is TFIIH an activator of the p53-mediated G1/S checkpoint? PMID- 7785073 TI - PCR on the gram-positive organism Frankia without prior DNA extraction. PMID- 7785072 TI - Mitochondria contaminate databases. PMID- 7785074 TI - Cloning of PCR fragments with a modified M13mp18 T-vector. PMID- 7785075 TI - Artefacts in protein-DNA interactions produced by DNA probes isolated using a transilluminator. PMID- 7785076 TI - Transcriptional regulation during the mammalian cell cycle. AB - Progression of the cell cycle in mammalian cells, as in all other organisms, is associated with the phase-specific transcription of defined sets of genes. Such periodically expressed genes frequently encode proteins that either directly control cell-cycle progression or function in metabolic processes linked to the cell cycle, such as nucleotide and DNA biosynthesis. Here, I summarize our current knowledge and views of the mechanisms governing the coupling of cell cycle control mechanisms to transcriptional regulation, with particular emphasis on the transcription factor E2F and its connections with cyclin-dependent kinases and the retinoblastoma gene family. PMID- 7785077 TI - Platyfish and swordtails: a genetic system for the analysis of molecular mechanisms in tumor formation. AB - Inspired by recent reports, many geneticists would agree that it is worth looking into aquaria or even replacing the Drosophila bottles in their laboratories with fish tanks. Indeed, encouraging results from large-scale mutagenesis screens in zebrafish have promoted this organism to a prominent position in the research of vertebrate developmental biology. Some other small aquarium fish species still inhabit side streams or backwaters of science, like the zebrafish did before, serving smaller communities of researchers as tools in fields such as developmental biology and neurobiology. One such type of fish is Xiphophorus, which offers a genetic system for the analysis of molecular mechanisms in tumorigenesis. PMID- 7785078 TI - Chicken genome mapping: a new era in avian genetics. AB - More than 460 loci representing either expressed or anonymous sequences have been mapped on to the first comprehensive molecular genetic linkage map of the chicken genome. Here, we review the current status of poultry genome mapping and discuss some of the new opportunities this provides. PMID- 7785079 TI - The elusive fertility genes of Drosophila: the ultimate haven for selfish genetic elements. AB - The Y chromosomes of Drosophila are necessary for male fertility. They carry giant genes that have some unconventional properties besides controlling the motility of the spermatozoa. Classical genetic and molecular studies suggest that evolution has favoured the close association between these genes and repetitive DNA sequences with 'selfish' traits. PMID- 7785080 TI - [Respiratory activity, ATP content and Rb+ transport in a cell culture after freezing-thawing]. AB - Energy-dependent processes and cation transfer in calf's kidney finite cell culture following freezing-thawing have been studied. It has been established that cell culture cryopreservation under the optimum conditions results in the reduction of breathing activity level, ATP, reduction of 86Pb+ general transfer ratio and increase of passive cation permeability of cytoplasmic membrane that indicates considerable changes of bioenergetic processes of recryopreserved cells. At the same time in the process of restoration of cell culture after it has been frozen and following two consecutive passages with application of enriched growth media, parameters of studied energy-dependent processes and cation membrane transfer system are completely restored. PMID- 7785081 TI - [Use of monoclonal antibodies for determining complement-binding activity of human immunoglobulins G in health and in chronic lympholeukemia]. AB - Mouse monoclonal IgG1-antibodies (MA) against melittin were used for the investigation of human IgG-C1q binding. The ELISA method, allowing one to determine the dissociation constants of IgG-C1q complex, based on the competition of two IgG (investigating human IgG and MA, labelled by peroxidase) for C1q binding was developed. The method was used to show that IgG in 50% of cases of chronic lymphoid leukemia possessed lesser complement-binding activity than normal human IgG. This effect can be the result of screening of effector centres of immunoglobulins by ligands which appeared in the process of tissue destruction under pathology. PMID- 7785082 TI - [Peptide hydrolases of marine organisms]. AB - The survey is devoted to the description of properties of proteolytic enzymes of some sea organisms. Structure peculiarities and properties of proteinases of trypsin and chymotrypsin type, carboxypeptidases A and B, aminopeptidase and leucine aminopeptidase of molluscs, stars, shrimps, fishes and other sea organisms have been considered. Data are presented about trypsins typical of the sea organisms which are characterized by high content of asparaginic and glutaminic acids and small values of activation energy of the reactions which they catalyse. Data are discussed concerning stability of enzymes as to heat denaturation, effect of the environment with external values of pH. Based on the similarity of the substrate specificity of enzymes, their sensitivity to inhibitors, it is concluded that the enzymes of the sea organisms and mammals are similar. PMID- 7785083 TI - [Correction of radiation injuries caused by low-intensity irradiation using antioxidants]. AB - The appearance of active oxygen form beginning and lipid peroxidation's activation (side by side with DNA injury) play the leading role in the mechanism of radiation injury. It is expedient to use antioxydants as prophylactic and early pathogenetic therapy remedies. The paper includes the survey of data from literature about usage of different classes of antioxidants (enzymes, vitamins, thiols and other) during prolonged low intensive radiation action. PMID- 7785084 TI - [Role of S'2-stimulation of serine proteases in regulation of proteolysis]. AB - Data about ligand specificity and functionality of the nearest surrounding of hydrolytic centre of serine proteases are presented. A regulatory role of S'2 site predetermining highly-specific activation of proenzymes into the enzymes and formation of stable enzyme-serine complexes is discussed. PMID- 7785085 TI - Protein phosphatases: function and regulation. AB - Thousands of proteins are expressed in a typical mammalian cell, of which a third are now thought to contain covalently bound phosphate. About 200 protein kinases and 100 protein phosphatases have already been identified. Whereas the classification, properties and regulation of protein kinases are largely studied, the information about the protein phosphatase is far to be completed. Relatively better is studied a group of serine/treonine protein phosphatases. It has been discovered that besides the control of the key enzymes of metabolic pathways, these phosphatases participate in the regulation of gene transcription and cell division in eukariots. In addition, the identification of tyrosine protein phosphatases points to a novel intracellular signalling pathways, controlling cell-cell communication, cell proliferation and signal transduction of receptors for peptide hormones and growth factors. The recent progress in these families of protein phosphatases is the topic of present review. PMID- 7785086 TI - Some evidence in favour of the partnership between rabbit muscle aldolase and glyceraldehyde 3-phosphate dehydrogenase in the consecutive reactions. AB - An additional indication in favour of interaction between sequential glycolytic enzymes is provided by the mutual enhancement of aldolase and glyceraldehyde 3 phosphate dehydrogenase activities. The efficiency of aldolase as the activator is progressively affected by the presence of its substrate, fructose-1,6 diphosphate, and its structural analogue, hexitol-1,6-diphosphate. Such interrelation of two sequential glycolytic enzymes can originate from their conformational interadjustment for the subsequent metabolic channeling between them. PMID- 7785087 TI - [Thermal sensitivity of Na+,K+-ATPase isoenzymes in the brain and kidney]. AB - Thermal stabilities of Na+, K(+)-ATP-ase preparations with different isozyme content from brain and kidneys of different animal species have been compared. The greater thermal lability of the alpha(+)-isoform of a catalytic subunit of Na+, K(+)-ATP-ase is established. The method of specific thermal inactivation of in brain preparations was used in comparative study of ouabain sensitivity of Na+, K(+)-ATP-ase isozymes from rat, cow and rabbit. It is concluded that the existing structural and functional model of the receptor site of Na+, K(+)-ATP ase catalytic subunit is not sufficient for the complete explanation of the species heterogeneity of Na+, K(+)-ATP-ase affinity to heart glycosides. PMID- 7785088 TI - [Isolation and some properties of protein inhibitor of trypsin from acorns of the oak tree]. AB - Four protein fractions with trypsin-inhibiting activity have been isolated from acorns of oak tree (Quercus robur L.) by chromatography on DEAE-cellulose. Further their purification on trypsin-agarose column have demonstrated 12 peaks of activity. Every fraction corresponded to these peaks, left the column with Sephadex G-50 with the same volume of elution that corresponded to molecular weight of 16000 +/- 10% dalton. It was concluded that they have the same protein inhibitor. All the fractions proved to be steady to high-temperature denaturation, 8 M carbamide and 0.1% SDS, but preserved not more than 20% of activity under dithiothreitol effect. All they had specificity to trypsin only and were significantly less active to chymotrypsin, peptine and pronase. PMID- 7785089 TI - [Ca2+ metabolism in the sarcoplasmic reticulum of skeletal muscle after surgical denervation]. AB - The ability of sarcoplasmic reticulum to regulate Ca(2+)-metabolism was studied at different terms after surgical denervation. The increase of Ca(2+)-ATP-ase activity, intensification of active Ca(2+)-accumulation under insignificant change of passive Ca(2+)-outflow from sarcoplasmic reticulum vesicles were observed 3-days after denervation. At more remote terms 14 days and 28 days after denervation all these parameters decreased except for Km: Ca(2+)-ATP activity and active Ca2+ accumulation decreased below normal level. PMID- 7785090 TI - [Interaction of anionic complex of palladium (II) with the bilayer lipid membrane]. AB - The interaction of anionic complex of palladium (II) with the bilayer phospholipid membrane (BLM) have been studied. It is shown that electric conductivity of membrane increases with the rise of concentration of the complex compound. The effect of the lipophilicity and polar properties of a cation on the transmembrane that carries this complex across BLM have been discussed. The mechanism of biological action of the compound under study is supposed. PMID- 7785091 TI - [Aggregation of neutrophils and their generation of active forms of oxygen as affected by lectins]. AB - It was shown that neutrophil aggregation is caused by all lectins with different specificity for carbohydrates but generation of active oxygen forms is induced only by some lectins. Polyspecific lectins-erythroagglutinin and phytohemagglutinins have the greatest activity in relation to both processes. PMID- 7785093 TI - [Antioxidant system of rat erythrocytes under conditions of prolonged intake of honeybee flower pollen load]. AB - The state of erythrocyte redox system of rats feeding on apis flower pollen load during a month was investigated. It was established that the content of glutathione, total SH-groups as well as activities of glutathione peroxidase and glutathione reductase in these animals in comparison with the control group were increased. Simultaneously a decrease of malondialdehyde and dienic conjugates in erythrocytes was shown. The activity of catalase and superoxide dismutase were increased, but it was not statistically reliable. A conclusion was made that the antioxidative system is nonspecifically activated and oxidative processes are blocked in erythrocytes of rats fed on apis flower pollen load. PMID- 7785092 TI - [Immunomodulatory effect of honeybee flower pollen load]. AB - Primary and secondary humoral immune response (the level of specific IgM and IgG) as well as the intensity of delayed-type hypersensitivity to sheep erythrocytes were investigated in rabbits fed with apis flower pollen load for a month. It is shown that apis flower pollen load is an immunomodulator. It stimulated humoral immune response and changed the reaction of delayed-type hypersensitivity. PMID- 7785094 TI - [Electron donor capacity of various amino acids]. AB - Constants of equilibria of reactions of 13 amino acids with I2 have been determined. It is shown that the values of constants are determined by the nature of side radicals. The highest values of donor-acceptor characteristics are noted in sulphur-containing amino acids, triptophan, low ones--in hydroxy-amino acids. It is shown on the example of flavonoid quertzetin that formation of donor acceptor bonds is characteristic of aminoacids parallel to the acid-base interaction. PMID- 7785095 TI - [Treatment of venous thromboses and pulmonary embolisms]. PMID- 7785096 TI - [Molecular biology and medical bacteriology]. PMID- 7785097 TI - [Anticoagulant and thrombolytic therapy in deep venous thrombosis and pulmonary embolism]. AB - During the last 10 years anticoagulant (AC) therapy and thrombolytic treatment of venous thromboembolism (VT) have been evaluated in randomized studies. Adjusted subcutaneous (s.c.) heparin and low molecular weight heparin (LMWH) are found at least as effective as intravenous (i.v.) infusion of heparin in deep venous thrombosis (DVT) without an increased bleeding risk. In pulmonary embolism (PE) randomized trials assessing the efficacy of s.c. heparin and LMWH are missing. Oral AC-treatment can be initiated from the first or second day in VT. The recommended duration is three months for medical patients, and 4 weeks seem appropriate for surgical patients that are completely mobilized and without persisting predisposing factors. Long-term efficacy of thrombolytic treatment of DVT has only been assessed in small trials showing a trend towards reduced risk of developing chronic venous insufficiency. Short-term thrombolytic treatment of DVT is evaluated in ongoing trials. In the treatment of PE short-term thrombolysis with either t-PA or urokinase is found to be as effective as long term thrombolytic treatment with a reduced bleeding risk. Thrombolytic therapy rapidly reduces embolic mass and stabilizes haemodynamics, but mortality and long term efficacy of thrombolysis and AC-treatment versus AC-treatment alone in PE are being assessed in ongoing studies. PMID- 7785099 TI - [Long-term prognosis of pulmonary sarcoidosis. 1. Prognostic value of lung function and symptoms]. AB - A follow-up of 254 patients with intrathoracic sarcoidosis has been carried out after a median of 27 years from diagnosis. All patients could be traced. No excess mortality was found (80 deaths observed versus 66 expected). The causes of death were related to sarcoidosis in 41%. X-ray stage was related to survival with a significant excess mortality for stage 3. Early clearing of X-ray changes gave a favourable vital prognosis. Survival was related to lung function, especially forced expiratory volume in 1 second (FEV1) and total lung capacity (TLC). All deaths from sarcoidosis were seen among patients with respiratory symptoms at presentation. For sarcoidosis & sarcoidosis-related deaths (N = 33), presence of one or more of the respiratory symptoms increased the risk significantly. For overall mortality respiratory symptoms were also significant predictors; this was the case even after adjusting for age, sex, x-ray stage and lung function (FEV1 & TLC) at presentation. In conclusion, no excess mortality was observed after a median of 27 years follow-up. Lung function, respiratory symptoms and to some extent X-ray stage at time of diagnosis influenced long-term mortality in patients with intrathoracic sarcoidosis. PMID- 7785098 TI - [Laser-assisted balloon angioplasty of occlusions in the femoropopliteal segment]. AB - During 1990 through 1992, 32 patients with arterial occlusive disease of the femoropopliteal segment underwent laser-assisted balloon angioplasty at the vascular service of Rigshospitalet, Copenhagen. A pulsed ultraviolet excimer laser was employed. Initial angiographic and clinical success was achieved in 20 of 32 femoropopliteal occlusions (63%). Life-table analysis revealed a cumulated patency rate of 40%, 33% and 25% after one month, one and three years, respectively. There was no correlation between initial success rate and length of occlusion, status of run-off, calcification or number of collateral vessels. In this series, laser angioplasty carried a high risk of perforation. The initial and long-term results were no better than could be expected of percutaneous transluminal angioplasty, suggesting that laser-assisted balloon angioplasty has no place in the vascular surgical armamentarium. PMID- 7785100 TI - [Long-term prognosis of pulmonary sarcoidosis. 2. Cardiac sarcoidosis and other extrapulmonary manifestations]. AB - Frequency and prognostic importance of extrapulmonary manifestations have been examined in 254 patients with intrathoracic sarcoidosis. A follow-up was carried out after a median of 27 years from diagnosis. All patients could be traced. Extrapulmonary manifestations were found in 119 patients (47%), mostly occurring within the first years after diagnosis of intrathoracic sarcoidosis; skin manifestations were most frequently seen. ECG-abnormalities were found in 35 patients (14%); in 17 cases in the form of sinus tachycardia. No excess mortality was found (80 deaths observed versus 66 expected). The causes of death were related to sarcoidosis in 41%. Only tachycardia was associated with an unfavourable prognosis and this association vanished after adjusting for decreased lung function. None of the other extrapulmonary manifestations were associated with an unfavourable vital prognosis. Erythema nodosum was of no prognostic significance concerning survival. In conclusion, extrapulmonary manifestations are frequent in patients with intrathoracic sarcoidosis but do not influence vital prognosis. PMID- 7785101 TI - [Respiratory tract infections in general practice--the effect of a medical audit project]. AB - A medical audit of the management of respiratory tract infections was performed among 31 general practitioners in Funen county. The first registration of prescriptions in 1992 showed that broadspectrum antibiotics were used to a higher extent than seemed necessary. An intervention with courses, visits to the department of clinical microbiology and distribution of recommendations concerning diagnosis and treatment was performed. The intention was to give the necessary and only the necessary amount of antibiotics and when an antibiotic was indicated to use penicillin as often as possible. A new registration was made one year after the first one. The proportion of antibiotic prescriptions was reduced from 0.49 to 0.38 and the proportion of prescriptions of broadspectrum antibiotics was reduced from 0.21 to 0.12. Detection of group A streptococci in tonsillitis was used more frequently in 1993 than in 1992. Medical audit performed after this model seems a good instrument for changing prescription habits. Medical audit thus seems to be a useful tool in quality improvement in general practice. PMID- 7785103 TI - [Unexpected cardiac arrest during combined spinal-epidural analgesia]. AB - A 58-year old man who had combined spinal-epidural anaesthesia for a total knee alloplasty suffered a sudden and unexpected cardiac arrest during an otherwise uncomplicated anaesthesia. The patient was promptly resuscitated by ephedrine i.v. The reason for the cardiac arrest is thought to be relative hypovolaemia. The importance of monitoring the patient, giving proper fluid-treatment and early use of ephedrine is emphasized. PMID- 7785102 TI - [Sick leave in relation to occupational environment and family conditions. An analysis of data from a study on health and morbidity performed 86]. AB - Data previously collected by the Danish Institute of Clinical Epidemiology (DICE) in 1986/87 by a structured interview of a sample of the adult Danish population was analysed to evaluate sick leave among 1) persons with preschool children, 2) persons with either physically demanding work or with exposure to chemicals, and 3) persons with mentally demanding employment. Average absence from work in the year previous to the interview was increased in unmarried women with preschool children (9.8 days). Average absence from work increased in a stepwise fashion from 4.7 to 18.7 days with increasing physical work loads, and from 5.6 to 10.1 days with increasing exposure to chemicals. In the group with mentally demanding work, the increased was from 6.3 to 20.0 days up to a load level of five. Risk of long lasting (above 10 days) sick leave was increased among the 52.9% of persons in the study base who either had physically demanding work or who were exposed to chemicals, prevalence rate 1.91 (1.56-2.35, 95% CI), as well as among the 20.9% of persons in the study base with mentally demanding work, prevalence rate 1.68 (1.38-2.05, 95% CI). Logistic regression analysis revealed statistically significant odds ratios also when age, tobacco smoking, marital status, chronic disease and overlap between the risk groups were taken into consideration. PMID- 7785104 TI - [Nitrogen oxide inhalation in acute pulmonary failure]. AB - Two cases of adult respiratory distress syndrome (ARDS) treated successfully with nitric oxide (NO) inhalation are described. One patient had severe sepsis and the other had trauma induced ARDS. The slow entry criteria for extracorporeal membrane oxygenation (ECMO) was fulfilled in both cases. NO inhalation substantially improved oxygenation, reduced pulmonary arterial pressure and peak inspiratory pressure. Treatment with NO inhalation was without side effects and easy to administer through the ventilator. Both patients survived without sequelae. We suggest that inhalation with NO should be tried before ECMO treatment is considered in severe ARDS. PMID- 7785105 TI - [Improved prognosis in breast cancer]. PMID- 7785106 TI - [The osteoporosis profile]. PMID- 7785107 TI - [The U-formed connection between alcohol and mortality]. PMID- 7785109 TI - [Lansoprazole--a new acid pump inhibitor]. PMID- 7785108 TI - [Blood alcohol and (air)traffic]. PMID- 7785110 TI - [The late results of the surgical treatment of vesicorenal reflux in children]. AB - 1-27-year follow-up results are available for 455 patients who at the age of 3 months-14 years were operated on vesicoureteral segments with reflux of the II, III and IV degree. Overall 648 interventions were made, of them 78 according to Gregoir-Lich (54 patients). Good results were obtained in 91.02% of cases (reflux degree II and III). Resection of distal ureter with its implantation into the bladder by Politano-Leadbetter technique was performed in 401 patients on 570 vesicoureteral segments. In reflux degree II and III good outcomes were reached in 97.37%, degree IV in 90.80% of the cases. Histological findings on the resected ureters showed that pathogenetically the reflux was initiated by structural changes in distal ureteral wall which occurred as a congenital or acquired condition. The removal of the destroyed segment contributed to advanced treatment effects. The reflux elimination favoured renal growth and clinical improvement of pyelonephritis. X-ray images of 150 kidneys (95 patients) 10-26 years after the reflux discontinuation reflected a 1.5-5-fold increase in the kidney size. Before stabilization parenchymal sclerosis developed the following 1 2 to 10-15 years. PMID- 7785111 TI - [The treatment of neurogenic hyperreflexic bladder dysfunctions in girls with low intensity laser radiation]. AB - 120 girls were investigated for the efficacy of three methods of treatment: conventional, infrared laser radiation on the projection of the bladder plus He Ne laser radiation on biologically active points (BAP), red He-Ne laser BAP radiation. All the patients suffered from neurogenic hyperreflexic dysfunctions of the bladder, 99.8% had the diagnosis of vegetovascular dystonia, 94.9% had sympathetic-tonic or mixed patterns. The combined laser exposure brought about the greatest response rate-90.0%. PMID- 7785113 TI - [The concept of the development of a Russian urology]. PMID- 7785112 TI - [Valves of the posterior urethra in children]. AB - The paper reports the analysis of 62 cases of posterior urethra valves treated from 1988 to 1993 in the Central Children's Hospital of Russia. The patients' age ranged from 6 months to 14 years. The patients were examined with the use of urethroscopy, urethrography and urodynamic tests providing accurate differential diagnosis of the urethral valves and other infravesical obstructions. Transurethral electroresection of the valvular cusps proved most effective treatment. There exists high probability of self cure of upper urinary tract complications after the transurethral resection (65%). The expectant policy should be followed in relation to vesicoureteral reflux and megaureter (3-6 and 6 12 months, respectively). The exceptions comprise the cases of the above reflux with marked lateralization, ectopy and exposure of ureteral ostia which are more effectively managed by simultaneous valvular transurethral resection and endoscopic submucous injections of teflon paste underneath ureteral ostia. The study of the prevalence of chronic renal failure suggested a conclusion on its equal occurrence in different age groups. PMID- 7785114 TI - [Lipid peroxidation in patients with nephrolithiasis and chronic pyelonephritis in the remission stage]. AB - Lipid peroxidation (LPO) was evaluated in 31 patients with nephrolithiasis and chronic pyelonephritis in remission. Chronic inflammation of renal parenchyma is shown to be associated with LPO activation. Urine diene conjugates excretion, plasma and red cell membrane malonic dialdehyde concentrations increase. LPO activation may contribute to maintenance of chronic renal inflammation in nephrolithiasis. PMID- 7785115 TI - [Xanthogranulomatous pyelonephritis]. AB - Based on the evidence obtained on 28 cases of xanthogranulomatous pyelonephritis (XP), the authors suggest to distinguish two XP clinical forms: obstructive and nonobstructive. The former may occur in noticeable destruction of renal tissue and urine retention secondary, most frequently, to long-standing nephrolithiasis. The latter simulates by symptoms and examination results renal carcinoma. In suspicion of nonobstructive XP, the surgeon should consider fast-made intraoperative biopsy to decide on feasibility of sparing intervention. PMID- 7785116 TI - [Varicocele in children and adolescents and infertility]. AB - 28 adolescents aged 16-18 were examined 2-4 years after correction of varicocele. Some ejaculate characteristics were found subnormal as well as the function of the prostate gland as indicated by reduced concentrations of citric acid and zinc ions. To make definite conclusions on possible effect of varicocele in adolescents on their future fertility further studies are necessary. PMID- 7785119 TI - [Clinical and diagnostic problems in angiomyolipoma of the kidney]. AB - 29 cases of angiomyolipoma (AML) reported in the paper illustrate clinical pictures and difficulties in this disease diagnosis. It is shown that when AML overgrows 5 cm in size it often provokes pain (13 cases), which ranks the first among AML symptoms. Ultrasonic differential diagnosis is not easy in large bleeding AML, in extrarenal AML location, whereas well and poorly vascularized tumors, the absence in them of clear-cut spiral arteries or aneurysm-like cavities cause much trouble for AML angiographic diagnosis. For the above causes computed tomography is also likely to provide misdiagnosis. A comprehensive approach to AML preoperative diagnosis brings about satisfactory results in 80% of the cases. PMID- 7785118 TI - [Arterial factors in the mechanism of penile erection]. AB - Hemodynamic study of the penis in diagnosis of erectile impotence is thought essential because many investigators have obtained evidence for involvement of vascular affections in the mechanisms of somatogenic erectile disturbances in 70 80% of the cases. The authors have assessed arterial and venous phases of penile hemodynamics in healthy males at rest and erection (28 subjects aged 24-56) and in 37 patients with functional sex disturbances aged 21-43. It was found that erection is maintained not only in participation of deep penile arteries, but also dorsal ones. This is also confirmed by synchronous changes in a.a. dorsalis et profunda penis circulation in response to sexual stimulation. However, more expanded network of arteriovenous anastomoses in the system of dorsal arteries makes hemodynamic changes in the course of erection less pronounced than in deep penile arteries. No hemodynamic alterations in the system of common iliac arteries during erection confirmed autonomic pattern of the processes running in penile vascular system. PMID- 7785120 TI - [The effect of a Rhodiola rosea extract on the incidence of recurrences of a superficial bladder cancer (experimental clinical research)]. AB - Oral administration of Rhodiola rosea extract to a small group of patents (n = 12) with superficial bladder carcinoma (T1G1-2) improved the characteristics of the urothelial tissue integration, parameters of leukocyte integrins and T-cell immunity. The average frequency of relapses for these patients has been found to fall twice, though statistical differences were not significant. PMID- 7785117 TI - [Azoospermia in patients with kidney diseases taking immunosuppressants long term]. AB - Ten sterile males of reproductive age previously treated with immunodepressants were examined andrologically. Azoospermia in them was treated with zinc sulfate (30-90 mg/day, 2-12 months), which was replaced by clomifen citrate in 6 of them (100 mg/day, 2-6.6 months). The response was recorded only in one male: zinc sulfate administration induced subnormal spermatogenesis improved by clomifen citrate as a result of which the patient became a father. In the rest cases azoospermia did not improve. Testicular biopsy performed in 3 patients detected the absence of cells of spermatogenic epithelium (del Castillo syndrome). The absence of response to stimulating therapy may indicate bad prognosis in azoospermia patients with renal diseases treated with immunodepressants. PMID- 7785122 TI - [The possibilities for arresting the progression of diffuse nephropathies]. PMID- 7785121 TI - [Rupture of the corpora cavernosa (clinical observations)]. AB - The authors performed emergency operation for rupture of the cavernous bodies in 2 patients whose urethra remained intact. The defect of the bodies and tunica albuginea was repaired by placing interrupted catgut sutures. Postoperative policy included antiinflammatory and resolving modalities. 10-year follow-up results were satisfactory. Complications did not occur. The patients retained sex function. PMID- 7785123 TI - [Computed renal angiography in the diagnosis of congenital hydronephrosis in children]. PMID- 7785125 TI - Ultrasonic B-mode image enhancement based on level-dependent spread functions. AB - The concept of level-dependent spatial summation is applied to the 2-dimensional amplitude distribution comprising an ultrasonic brightness image. The distribution is convolved with a level-dependent kernel. The size (i.e., extent) of the kernel is inversely proportional to the local signal level. The result is a 2-dimensional distribution of Mach bands, accentuating edges and providing useful information for the reduction of speckle. In addition, a small but powerful extension of the processing scheme is presented that supports global edge enhancement and contrast enhancement. The level of improvement has been quantified in terms of an increase in the lesion signal-to-noise ratio on the order of 60 percent. Only two system-dependent parameters have to be supplied for adjustment. The algorithm is rather insensitive to the exact choice of the parameters, making it quite robust. Since only a limited number of simple operations is required for the processing of a frame, the algorithm is expected to be suitable for real time application. PMID- 7785124 TI - [The central hemodynamics and hormonal status before, during and after urologic operations in children]. AB - Urological operations in children are made as a rule to correct congenital malformations. The prevention of operative injury to the child' body is secured only in conditions of adequate anesthesiological defense. This is possible only in availability of rapid information on cardiovascular, oxygen metabolic and hormonal statuses. Central hemodynamics, oxygen metabolism and hormonal findings have been summarized for 89 children. The above parameters were measured before and during plastic reconstruction of the upper urinary tract. Initially hyperkinetic hemodynamics because of inadequate premedication to control psychoemotional lability, changed for stable and hypokinetic circulation to the end of the operative intervention as a result of neuroleptanalgesia. Eukinetic trends were induced by balanced promedol analgesia throughout the operation. Concentrations of hydrocortisone, aldosterone and STH were on the increase, while T3 and T4 levels lowered. Hyperkinetic and eukinetic hemodynamics were observed postoperatively after neuroleptanalgesia and balanced promedol-including analgesia, respectively. PMID- 7785126 TI - An efficient real time focusing delay calculation in ultrasonic imaging systems. AB - An efficient real time focusing delay calculation algorithm is proposed for variable sampling clock generation (SCG) with high accuracy needed in digital focusing in ultrasonic imaging systems. The proposed algorithm is an extension of the midpoint drawing algorithm that is well known in the computer graphics area. It can be implemented with simple hardware amenable to VLSI realization, without using a large amount of look-up memory to store the sampling clock information otherwise required. PMID- 7785127 TI - Postprocessing of velocity distributions in real-time ultrasonic color velocity imaging. AB - A robust processing scheme is proposed that improves the presentation of 2 dimensional velocity distributions in real-time ultrasonic color velocity images. Essentially, the algorithm is a modification of a first order recursive filter, processing each velocity signal in the spatial distribution separately from the others. It restores the sudden holes and notches in the velocity profiles that occur whenever the observed blood velocity is incidentally close to zero. At the same time, unlike conventional persistence filters, it does not influence any of the true velocity information that is measured. The result is a consistent sequence of color velocity images with smooth transitions between the borders of the consecutive velocity profiles and with an improved definition of the regions containing blood. PMID- 7785128 TI - Ultrasound echo envelope analysis using a homodyned K distribution signal model. AB - The statistics of ultrasound echo envelope signals can be used to characterize scattering media. The Rayleigh distribution and its generalized forms, the K and Rice distributions, have been previously used to model the echo signal. A more generalized statistical model, the homodyned K distribution, combines the K and Rice distribution features to better account for the statistics of the echo signal. We show that this model can give two parameters that are useful for media characterization: k, the ratio of coherent to diffuse signals, and, beta, which characterizes the clustering of scatters in the medium. PMID- 7785130 TI - [Immune response to Epstein-Barr virus in patients with otorhinolaryngologic neoplasms of various morphology and invasiveness]. AB - Both nasopharyngeal and tumors and epithelial cancer of topographically different sites of the mouth, laryngopharynx are shown to be associated in many cases with high immunity to virus Epstein-Barr (VEB) antigens. VEB-associated antibody quantitation in patients with laryngeal, laryngopharyngeal, oral and lingual cancer revealed that the malignant process dissemination and the tumor differentiation are related to immune response to VEB antigens: the more advanced is cancer and the poorer is its differentiation, the more pronounced is the immune response. PMID- 7785129 TI - [Clinical and morphological characteristics of verrucous carcinoma]. AB - Verrucose carcinoma is well differentiated squamous carcinoma characterized by exophitic growth, slow surface spread, marked lymphoplasmocytic infiltration and fibrosis of submucosal lining. Verrucose carcinoma runs relatively benign course, is effectively treated surgically, is prognostically favourable. There are cases free of both metastases and recurrences for postdiagnosis 15 years. PMID- 7785131 TI - [Prognostic significance of tumor necrosis in cancer of laryngeal vestibule]. AB - The degree of tumor necrosis in 245 patients with squamous cancer of the larynx were graded as: pronounced necrosis (group I), moderate necrosis (group II), insignificant necrosis (group III), absence of necrosis (group IV). Regional metastases were identified in 39%, 32%, 28.5%, 18.5% of the patients from groups I, II, III and IV, respectively. Five-year survival was, respectively, 53, 70, 14 and 78%. Tumor necrosis severity seems to be more prognostically significant than differentiation of squamous carcinoma. PMID- 7785132 TI - [Repeated adenoidectomy and prevention of the recurrence of adenoid hypertrophy]. AB - Basing on comprehensive clinical experience and the analysis of long- and short term results of adenotomy, the author evaluates the effectiveness of this procedure, the causes of residual nasal respiration problems. The main reason of postoperative incomplete restoration of nasal respiration is suggested to be nonradical removal of the adenoid tissue which may result from specific features of the adenoids size, location, anatomical structure of the nasopharynx, the surgeon's equipment and experience, etc. The author thinks postadenotomy nasal problems should be managed with repeat operation which is recommended in the literature and has been practiced by the author for 30 years with the overall efficacy of 90%. Clinical symptoms, indications to repeat surgery are provided. Repeat adenotomy in a few days after the initial operation permits the author to reduce the percent of the vegetations recurrences in many patients. PMID- 7785133 TI - [Clinical and biochemical aspects in the treatment of acute maxillary sinusitis with antioxidants]. AB - A trial has been made of traditional versus antioxidant treatment of acute maxillary sinusitides. The patients were injected a mixture consisting of 4 ml emulsion of 10% dibunol liniment and 2 ml of 5% ascorbic acid made by dilution of 10 g dibunol in 30 ml sterile 0.5% novocaine solution. The mixture was introduced into the sinuses 2 times a day, in one of the study groups it was combined with 500,000 U of ampicillin in cases of purulent sinusitis. In catarrhal form the mixture was injected once a day without the antibiotic. Control groups received 4 ml dioxidine in a single dose after the sinus lavage in catarrhal sinusitis and 500,000 U ampicillin plus hydrocortisone emulsion (1 ml in 4 ml solution) 2 times a day in case of purulent sinusitis. All the patients received aevit (one capsule daily). The mean number of manipulations for the study groups were 4.4 +/- 0.4 in catarrhal sinuses and 6.3 +/- 0.5 in purulent sinusitis; in control groups, respectively, 5.9 +/- 0.5 and 10.7 +/- 0.7. Mean duration of treatment reached 5.3 +/- 0.4, 6.2 +/- 0.3 and 7.1 +/- 0.1 in the study groups and 8.5 +/- 0.2, 10.2 +/- 0.4 days in the control groups. Positive response to the treatment with antioxidants was confirmed by positive changes in blood levels of LPO products, activity of lysosomal hydrolases and antioxidant defense enzymes. The results obtained justify the inclusion of antioxidants in the schemes of acute sinusitis treatment. PMID- 7785134 TI - [Peripheral nervous system in children with chronic inflammatory otorhinolaryngologic diseases]. AB - A comparative evaluation of central and vegetative nervous as well as cardiovascular systems in 20 normal children and 45 patients with ENT problems found out vegetative lability in 8 children. Three of them were from the control healthy group, 4 had tonsillitis, 1 purulent sinusitis. These children were referred to the vegetative dystonia risk group. In 28 patients (9.3 and 16 cases of purulent-polypous, purulent and decompensated tonsillitis, respectively) parasympathicotonic and sympathicotonic shifts revealed in the baseline vegetative tone and vegetative reactivity require adequate therapeutic correction. PMID- 7785135 TI - [Complications of ENT diseases as a criterion in the evaluation of physician's competency]. PMID- 7785136 TI - [Computed tomography in the diagnosis of postoperative changes of paranasal sinuses]. AB - Basing on the evidence obtained at examinations of 37 patients within 15-year follow-up after surgery on the maxillary and ethmoidal sinuses, the authors analyse potentialities and techniques of computed tomography in diagnosis of the developments in operated on paranasal sinuses. CT demonstrated advantages in examination of paranasal sinus walls and soft tissue alterations in them. PMID- 7785137 TI - [The syndrome of sphenopalatine ganglion]. AB - The author considers a rare disease of the sphenopalatine ganglion known in the literature as Sluder's syndrome. In view of the ganglion anatomical structure and connections with afferent and vegetative formations of the face and skull, clinical presentation of the syndrome various greatly. The author analyses the causes of the disease, its differential diagnosis, methods of treatment, gives a case report of a male patient who has been followed up for 26 years to illustrate the complicacy of Sluder's syndrome diagnosis. PMID- 7785138 TI - [An unusual foreign body in the larynx]. PMID- 7785139 TI - [Injury of internal carotid artery and internal jugular vein during emergency laryngotomy in an infant]. PMID- 7785140 TI - [Chronic asymptomatic foreign body in the frontal sinus]. PMID- 7785141 TI - [Chronic suppurative polypous sinusitis complicated with rhinogenous basal meningoencephalitis with impairement of the V,VI,VII,VIII,X,XI cranial nerves]. PMID- 7785142 TI - [Metastasis of kidney cancer into the maxillary sinus]. PMID- 7785144 TI - [Diagnostic significance of eye movements in otoneurology]. PMID- 7785143 TI - [A case of chronic foreign body in the nasal cavity]. PMID- 7785145 TI - [Statistics and prehospital diagnosis of malignant neoplasms of upper respiratory tract in Russia]. AB - In 1990 in Russia there were 12,264 newly diagnosed cases of upper respiratory tract cancer and 7562 relevant lethal cases. The authors provide data on such cancer incidence rate by site, groups of population, sex, age, type of tumor. Standardized incidence and mortality rates for various regions of Russia are indicative of the trend to the rates increase and relevant economic losses. The emphasis is on late diagnosis of ENT cancer, as 70-85% of the patients start anticancer treatment in advanced stages of the disease. This shows unsatisfactory situation in prehospital diagnosis of such tumors, numerous cases of misdiagnosis. The authors express their concern about poor oncological qualification of the practicing ENT specialists and urge improvements in current system of otorhinolaryngological training, performance of updated prophylactic and diagnostic measures. PMID- 7785146 TI - [Methods in the control of educational level in ENT students]. PMID- 7785147 TI - [Effect of cryotherapy and laser destruction on experimental model of human vascular tumor]. AB - Macro- and microscopical changes in the biological model of hemangioma, hen's comb, were assessed to compare the effectiveness of cryotherapy, CO2-, YAG-Nd- and copper vapour (in the green part of the spectrum) laser radiation. The best results were obtained upon exposure to laser on copper vapour and SO2-laser of minor capacity. PMID- 7785148 TI - [Rhinologic and otoneurologic tests in the diagnosis of nasal liquorrhea and their significance in the choice of surgical treatment]. AB - Liquorrhea nasalis (LN) is considered by ENT specialists as vasomotor--allergic rhinitis. It is divided into craniosinusonasal and cranionasal. The latter form is more dangerous as to intracranial complications. Otorhinolaryngological and otoneurological examinations of LN patients are essential in the disease diagnosis, evaluation of surgical results (by nasal endoscopy), detection of intranasal medullary hernia, liquor cysts and tumors as well as residual otoneurological symptoms consequent to meningitis, brain trauma, etc. In choice of surgical treatment the attention of the physician should be directed to concomitant intranasal hernias and liquor cysts, tumors, purulent sinusitis. Out of 70 LN cases residual symptoms of olfactory disorders were recorded in 35%, neurosensory hypoacusis in 30% of the cases. The best position of the patient and relevant facilities for identification of even minimal LN are described. PMID- 7785149 TI - [Use of sinus catheter "Iamik" in children]. AB - Sinus catheters were inserted in 44 children (mean age 8.5 years) suffering from acute and chronic purulent polysinusitis. In 33 outpatients sinus catheterization was combined with nasal irrigation providing a persistent therapeutic effect on the inflammation focus. In view of good treatment results both methods are offered for inpatient and outpatient pediatric practice of treating sinusitis. PMID- 7785151 TI - [Time factors in the acoustic reflex of intra-aural muscles and brain stem acoustic evoked potentials in workers with occupational hearing loss and normal and delayed speech discrimination]. AB - Time characteristics of brain stem acoustic evoked potentials and acoustic reflex of the intra-aural muscles were measured in workers with occupational hypoacusis having normal and delayed capacity for speech discrimination. The findings provided evidence for inhibition of speech information analysis at the level of the brain stem and dissociation of interaction between the brain stem nuclei. PMID- 7785152 TI - [Post-traumatic rehabilitative treatment of hollow neck organs]. AB - The attention of the reader is focused on the errors and shortcomings in rendering urgent emergency care for patients who underwent traumas of the neck hollow organs. The 30-year experience with 1000 patients managed by the authors convinced him of the necessity to consider more carefully the medical history of the patient, to use more frequently Killian's and Brunings's examinations, microlaryngoscopy, fibroendoscopy, x-rays. Restorative treatment becomes more effective under ultrasound and laser separation of the tissues, laryngochioido plexy, tracheopexy with establishment of the laryngeal patency and that of trachea. The technique is proposed for broadening the lumen of the cervical trachea in cicatricial stenosis and in going-on scarring in the thoracic trachea. The progress in the surgery of the neck hollow organs depends on adequate facilities and treatment policy. PMID- 7785150 TI - [Thromboelastography of blood coagulation in patients with complicated nasal furunculosis]. AB - The study of blood coagulation in 50 patients with complicated nasal furuncle using thromboelastogram indicated that such patients have hypercoagulation correctable by intravascular laser radiation. Thromboelastography proved a reliable objective technique in evaluation of blood coagulation this promoting a valid choice of therapeutic policy in complicated nasal furunculi. PMID- 7785153 TI - [Diagnosis of pharyngeal and laryngeal diphtheria in adults]. AB - 142 adults with pharyngeal and laryngeal diphtheria were registered in Yekaterinburg in 1993. Of them, 136 patients recovered and 6 died. The analysis of the clinical features and diagnostic errors showed that subjects with chronic visceral diseases and alcoholics are more likely to have poor prognosis of diphtheria. Diphtheria manifested primarily with edema followed by infiltration of the mucosa, with appearance of thin transparent furs, tenderness of cervical regional lymph nodes. The typical greyish-brown thick and firm false membranes occurred only in the late stage of the disease. The features of the diphtheric croup in the adults complicated the diagnosis. These were, unlike croup in children, the vagueness of the stages of this syndrome, rapid involvement of the trachea and bronchi, mixed type of dispnea and delirious state in alcoholics. It is necessary to set up the duty of ENT specialists in the diagnostic departments of the infectious hospitals for repeated endoscopic and bacteriologic examinations of the diphtheria suspects. PMID- 7785154 TI - [Allergy and acute stenosing laryngotracheitis in children]. AB - An allergological examination of 144 patients suffering from acute stenosing laryngotracheitis revealed food, drug, bacterial allergy of exudative diathesis in 62.5% of the cases. Allergic children had laryngostenosis of degree II and more advanced two times more frequently, whereas recurrences (12 cases) occurred primarily in children in premorbid condition. Allergy of shown to contribute to the onset of acute stenosing laryndotracheitis as allergic subjects are more susceptible to respiratory bacterial and viral infection. Local factors are mostly responsible for this. The author offers recommendations on more advanced treatment of acute stenosing laryngotracheitis with consideration of allergic aspects. PMID- 7785155 TI - [Occupational diseases of upper respiratory tract caused by ecologic factors]. AB - The author considers evidence for a close relationships between industrial zone pollution with irritants, allergens and diseases of the upper respiratory tracts. The investigators emphasize that 80% of the subjects exposed to the above pollution at their jobs develop chronic dystrophy and allergy affecting nose, pharynx and larynx. PMID- 7785157 TI - [Use of collagen in otorhinolaryngology]. PMID- 7785156 TI - [Critical and emergency medical care in ammonia intoxication of upper respiratory tract]. AB - 37 subjects were admitted to hospital after the accident which caused their exposure to liquid ammonia which produced respiratory lesions in 29 of them. The severity of the respiratory damage depended on oxygen insufficiency (stenosing laryngeal or tracheal bronchitis, pneumonia) and intoxication. Multimodality treatment resulted in cure of 24 patients, 3 patients improved, 2 patients died. The authors think it proper to place such victims into general hospitals where multiprofile care can be rendered including that of ENT specialist whose care proved necessary for the majority of the above patients. Subjects exposed to ammonia can be transported to distant hospitals as the symptoms worsen gradually. PMID- 7785159 TI - [Chronic sinusitis complicated with multiple brain abscesses]. PMID- 7785158 TI - [Physical therapy of otorhinolaryngologic inflammatory diseases]. AB - The paper reviews clinical, morphological, immunological and biochemical effects on acute and chronic inflammation in the upper airways and the ear produced by the exposure to cryoeffects, He-Ne or infrared laser radiation, ultraviolet blood radiation. The original advanced procedures developed by the author seem superior to conventional approaches to diagnosis and treatment of ENT inflammation. PMID- 7785160 TI - [A rare case of malignant trichoepithelioma of the external acoustic meatus]. PMID- 7785161 TI - [Development of scientific research of professor Undrits V.F., member of Academy of Medical Sciences of USSR, in the works of Leningrad Scientific Research Institute on ear, larynx, nose and speech diseases]. PMID- 7785162 TI - [Intravascular laser irradiation of the blood in the treatment of suppurative septic complications in otorhinolaryngology]. AB - The paper reviews the results of intravascular laser radiation (ILR) for pyoseptic complications in 8 patients with otogenic and 2 patients with rhinogenic meningitis, 1 patient with cavernous sinus thrombosis and 5 patients with Dupuytren's phlegmon. The adjuvant to conventional treatment use of ILR activates immune system, improves rheological blood characteristics, enhances tissue regeneration. PMID- 7785163 TI - Clinicopathologic evaluation of the liver. AB - Clinicopathologic data are important tools in the evaluation of a patient with liver dysfunction. It is imperative, however, that the data not be looked at with a dogmatic approach. Many of the laboratory tests are sensitive indicators of hepatic dysfunction; however, they seldom, if ever, indicate a specific cause of hepatic dysfunction. History, physical, radiographic, and ultrasonographic examination findings, and laboratory data must be used together to fully evaluate a patient with biochemical abnormalities related to hepatic function. The prevalence of secondary hepatic disease and the difficulty of differentiating it from primary hepatic disease based on laboratory data must always be kept in mind. PMID- 7785164 TI - Hepatic aspiration and biopsy techniques. AB - Hepatic biopsy can be a key part of the diagnostic plan in dogs or cats with liver disease. There are a wide variety of techniques for the clinician to choose from based on the patient's condition, liver size, equipment available, experience of the operator, and financial considerations. Although major complications are rare, the clinician should not attempt a biopsy procedure without being prepared to diagnose and treat complications appropriately if they occur. Many techniques for hepatic biopsy are easy to learn and to perform and should be a part of small animal practice at every level. PMID- 7785165 TI - Interpretation of liver biopsies. AB - Liver biopsies help define the disease process and can assist the clinician in forming a prognosis. The small size of liver biopsy specimens and limited responses of the liver to a wide spectrum of injuries often do not allow for a specific etiologic diagnosis. Determination of the distribution and morphology of the lesion often provides useful diagnostic and prognostic information. Maximum value can be attained from liver biopsies when the histologic findings are correlated with the results of other diagnostic tests and there is good communication between the clinician and pathologist. PMID- 7785166 TI - Hepatic imaging with radiology and ultrasound. AB - Radiographically, the diseased liver may change in size, shape, position, or opacity. Contrast studies such as peritoneography, cholecystography, portography, and arteriography may be performed to increase the specificity of the radiographic diagnosis. Ultrasound can be used to detect the changes in liver echogenicity associated with disease, identify focal verses diffuse disease processes, detect vascular and biliary abnormalities noninvasively, and direct needle aspirates and biopsies for culture, cytology, and histopathology. PMID- 7785167 TI - Hepatic encephalopathy: clinical signs, pathogenesis, and treatment. AB - Hepatic encephalopathy is a metabolic encephalopathy that is completely reversible if treated early and appropriately. It is seen most commonly in dogs and cats with portosystemic portal hypertension. Antibiotics, lactulose, and dietary manipulation should be initiated as soon as hepatic encephalopathy is suspected. The prognosis of hepatic encephalopathy is complex and is not completely understood. PMID- 7785168 TI - Feline idiopathic hepatic lipidosis. AB - Feline IHL is a severe hepatopathy that can be treated by aggressive nutritional support. Until the underlying mechanisms of protein and lipid metabolism are understood in both healthy and ill cats, dietary therapy remains supportive. It is likely that the pathogenesis of IHL in cats is multifactorial, involving both increased fatty acid mobilization to the liver and a defect in oxidation of fatty acids or removal of VLDL. It is also possible that individual variation may play a role in the development of this disease in cats undergoing starvation. Continued studies will focus on the unique pathways of hepatic metabolism in the cat, and how these pathways are altered, leading to hepatic lipid accumulation and clinical disease. Hopefully, these studies can be applied to the prevention or treatment of IHL in cats. PMID- 7785169 TI - Feline cholangiohepatitis complex. AB - Feline cholangiohepatitis complex causes a diffuse intrahepatic cholestasis of unknown etiology. Recognized histologic forms include acute suppurative cholangitis/cholangiohepatitis, long-term nonsuppurative cholangitis/cholangiohepatitis, and biliary cirrhosis. Treatment of cholangiohepatitis complex varies based on histologic type. Thus a liver biopsy is necessary for definitive diagnosis and treatment. Because cholangiohepatitis complex causes diffuse hepatic change, percutaneous needle biopsies are often sufficient for obtaining a diagnosis. Antibiotics are used to treat all forms of feline cholangiohepatitis complex, but steroids may be of equal or greater importance for use in the treatment of long-term nonsuppurative cholangiohepatitis. Prognosis is guarded for cats with any form of cholangiohepatitis complex due to the variable response to treatment seen in many cats. Spontaneous remission occasionally occurs. PMID- 7785170 TI - Chronic hepatitis in dogs. AB - Chronic hepatitis in dogs is not one disease but a diverse group of diseases, resulting in a common clinical and clinical pathologic picture. Viruses, leptospires, other infectious agents, drugs, hereditary factors, and autoimmunity have all been associated with hepatic disease leading to chronic hepatitis in dogs. In most cases of canine hepatitis, the etiology is unknown. Biopsy and histopathology are needed to establish a diagnosis, possible etiology, and prognosis. Treatment is mostly supportive. In some cases of chronic active hepatitis, corticosteroid therapy is appropriate. Sequential liver biopsies are the best way to monitor progress. PMID- 7785171 TI - Copper-associated hepatopathies in dogs. AB - Copper-associated hepatotoxicity in certain breeds has been identified for almost 20 years, and the list of affected breeds is growing. The importance for copper analysis of liver specimens is emphasized by the realization that copper accumulation occurs in many hepatic disease states, and it may become pathologic. Many treatment possibilities exist. It is important that therapy be tailored to the needs of the animal and the severity of accumulation. To determine efficacy of treatment and when an endpoint has been reached, follow-up liver biopsies are essential. PMID- 7785172 TI - Hepatic neoplasia in the dog and cat. AB - The histopathologic types of liver tumors in dogs and cats are reviewed with particular emphasis on the presenting signs and distribution within the liver. Ultrasonographic findings are discussed, as well as laboratory abnormalities. Finally, treatment options, prognoses, and survival times are presented, including chemotherapy protocols. PMID- 7785173 TI - The diagnosis and management of acute liver failure in dogs and cats. AB - Management of the small animal patient with a presumptive diagnosis of acute liver failure should aim to provide high quality supportive care aimed at the functional derangements that occur. A definitive histopathologic diagnosis should be pursued to allow evaluation of the reversibility of the underlying condition. With the current advances in veterinary critical care, improved medical and technical management should reduce both morbidity and mortality in the patient with potentially reversible liver failure. PMID- 7785174 TI - Management of portal hypertension and its consequences. AB - Increased pressure in the protal venous system results from impedance to blood flow at any point along it's course from the splanchnic circulation through the liver to the right heart. Typical manifestations of sustained increases in portal venous pressure commonly may include accumulation of abdominal fluid and development of acquired portosystemic shunts. Pathophysiology of altered portal vascular dynamics, diagnostic approach for animals suspected of having an intra abdominal source of portal hypertension and treatment options are discussed. PMID- 7785175 TI - Nutritional management of liver disease. AB - The provision of adequate nutrition to the patient with liver disease is a challenge. The practitioner must avoid overwhelming the remaining metabolic capabilities of the damaged organ. The ability of the liver to regenerate and the patient to recover depends on the availability of sufficient nutrients. There is no default diet for the patient with liver disease. Each patient must be evaluated individually, with consideration given to the type and origin of the liver disease, the current extent of hepatic dysfunction, and the patient's previous dietary history. Efforts should be directed at the provision of an energy intake adequate to maintain body weight and a protein intake as close to normal as can be tolerated without precipitating signs of hepatic encephalopathy. PMID- 7785176 TI - Bile acids in the diagnosis, pathology, and therapy of hepatobiliary diseases. AB - Bile acids are normally confined in the enterohepatic circulation in which they play an important role in bile formation, biliary lipid excretion, and intestinal lipid absorption. In hepatobiliary diseases, bile acids escape the confinement of the enterohepatic circulation, allowing the measurement of the serum total bile acid concentration as a diagnostic indicator. Accumulation of certain bile acids within the hepatocyte, amplified as a consequence of cholestatic hepatobiliary disease, probably enhances cytotoxicity and leads to secondary pathology. Ursodeoxycholate, a bile acid with atypical physiological effects, may be useful in the treatment of various long-term cholestatic hepatobiliary diseases. Presently, most of the information on the toxicity and therapeutic usefulness of bile acids are based on studies in humans and experimental animals. Further studies, both basic and clinical, are needed to determine the pathologic as well as the therapeutic effects of bile acids in domestic animals. PMID- 7785177 TI - Treatment of naturally occurring sheep scab (Psoroptes ovis infestation) in the United Kingdom with ivermectin. AB - An outbreak of naturally occurring sheep scab in a flock of 207 sheep was successfully treated with three consecutive weekly subcutaneous injections of ivermectin at a dose rate of 200 micrograms/kg. Plunge dipping ewes during early pregnancy was not considered appropriate on welfare grounds. PMID- 7785178 TI - Ultrasonographic examination of the small intestine of cows. AB - The small intestine of 50 cows was examined ultrasonographically with a 3.5 MHz linear transducer. The cows were examined on the right side, from the tuber coxae to the eighth intercostal space and from the transverse processes of the vertebrae to the linea alba. The appearance of loops of small intestine and their contents and motility were assessed. In the majority of cases, the intestine contained feed and the contents appeared hyperechoic, but in some cows, the intestinal lumen contained mucus or fluid which was hypoechoic. The cranial part of the duodenum could be viewed longitudinally and in cross-section: its largest diameter varied from 1.1 to 5.4 cm and it could be identified with certainty only medial to the gall bladder, which served as an acoustic window. The descending part of the duodenum was adjacent to the abdominal wall and was enveloped in the hyperechoic greater omentum, differentiating it from the jejunum and ileum. The largest diameter of the descending part of the duodenum varied from 0.9 to 3.7 cm. The ascending duodenum could not be identified because of its anatomical position. Loops of jejunum and ileum were usually viewed in cross-section and sometimes longitudinally; in contrast with the duodenum, they were constantly moving. The average diameter of the jejunum and ileum varied from 2.2 to 4.5 cm. PMID- 7785180 TI - Sudden death in dairy cattle with putative acute aflatoxin B poisoning. PMID- 7785179 TI - Canine Lyme disease in Belgium. AB - Lyme borreliosis is a multisystem disease caused by the tick-borne spirochaete Borrelia burgdorferi. In addition to causing human illness, borreliosis has been recorded in many species of mammals, including domestic animals which come into contact with the infected tick vector. This paper describes the first two cases to the authors' knowledge of Lyme borreliosis in dogs in Belgium. Both animals suffered recurrent lameness and general prostration. In addition, one of the dogs had recurrent paralysis of nerves V, VII, IX and X, leading to dysphagia and total bilateral paralysis of the mandibular muscles. This complication of Lyme borreliosis has been well documented in human pathology, but has not previously been recorded in the veterinary literature. PMID- 7785181 TI - Serological survey for swine vesicular disease in the UK. PMID- 7785182 TI - New rules on medicines. PMID- 7785183 TI - New rules on medicines. PMID- 7785184 TI - Future of the State Veterinary Service. PMID- 7785185 TI - Ethics of farm animal exports. PMID- 7785186 TI - Peracute pleuropneumonia in adult cattle. PMID- 7785187 TI - Detection of antibodies against Actinobacillus pleuropneumoniae, serotype 2 in porcine colostrum using a blocking enzyme-linked immunosorbent assay specific for serotype 2. AB - A blocking enzyme-linked immunosorbent assay (ELISA) developed for detection of antibodies to Actinobacillus pleuropneumoniae serotype 2 in sera from pigs (Nielsen et al., 1991) was evaluated for its suitability to detect antibodies in colostrum to this serotype. Using colostrum from sows experimentally infected with serotype 2 and from herds known to be infected with this serotype, the sensitivity of the test was 100%. Antibodies to A. pleuropneumoniae serotype 2 could be detected in colostrum of experimentally infected sows until at least 5 days after farrowing. Positive results were not observed with colostrum samples from herds known to be free from A. pleuropneumoniae. The high diagnostic sensitivity and specificity of the assay indicated that screening of herds for A. pleuropneumoniae serotype 2 infection by testing colostrum would be a reliable and simple method for herd monitoring. PMID- 7785188 TI - Identification of herd-specific bovine viral diarrhoea virus isolates from infected cattle and sheep. AB - Thirteen pestiviruses isolated from ruminants on four different farms in Sweden were compared antigenically and genetically. On two farms, viruses were isolated from both cattle and sheep, a third farm contained only sheep and a fourth only cattle. Seven viruses were isolated from six different cattle and six viruses were isolated from five different sheep. Epitope conservation between the viruses was studied with a panel of 32 monoclonal antibodies, revealing that all of the isolates were BVDV-like. However, certain epitopes present in isolates from cattle were lost following virus transmission to sheep. In vitro amplification of the 5'-untranslated region of the 13 isolates by the polymerase chain reaction (PCR) and subsequent analyses of amplified products with restriction enzymes also indicated that all 13 isolates belong to the BVDV group of pestiviruses. A fragment of the E2 (gp53) gene of each virus was amplified by PCR and a comparison of the amplified sequence of 188 nucleotides separated the isolates into four groups each of which could be identified with a particular farm of origin. The 13 isolates were thus herd-specific rather than species-specific demonstrating that BVDV is readily transmitted between cattle and sheep. PMID- 7785189 TI - Chemiluminescent detection of caprine arthritis encephalitis virus with a PCR generated single stranded nonradiolabelled probe. AB - A 814-bp digoxigenin-labelled single stranded DNA probe was produced and utilized in slot-blot hybridization for detection of caprine arthritis encephalitis virus (CAEV) in goat synovial membrane (GSM) cell culture infected with CAEV. The sensitivity of a PCR-generated probe was compared with a random primer labelled probe. The probe with digoxigenin-dUTP incorporated in the PCR reaction mixture was more sensitive for RNA detection than the random primer probe and it was much simpler to use. The probe was applied for detection of CAEV by blot blot hybridization in peripheral blood mononuclear cells (PBMC) and macrophage cultures obtained from naturally infected goats. This technique was not sufficiently sensitive to detect the viral nucleic acid directly from PBMC or cultured macrophages. When macrophages were cultured in vitro and then cocultured with susceptible GSM cells, samples gave a positive signal in the slot-blot hybridization technique. The use of slot-blot RNA hybridization permits more convenient and rapid confirmation of CAEV isolation in susceptible cells than the conventional identification by syncytia formation. PMID- 7785190 TI - Rapid method utilizing the polymerase chain reaction for detection of canine parvovirus in feces of diarrheic dogs. AB - By using primers based on the sequence of the VP2 gene of canine parovirus (CPV), we established a rapid and specific assay for identification of the virus from fecal specimens based on the polymerase chain reaction (PCR). By use of a pair of primers, a specific 226-bp sequence was amplified by the PCR. All strains of CPV tested gave a specific amplification product by the PCR, while neither porcine parovirus nor host cell did so. The PCR assay can detect fewer particles of CPV than the conventional methods, being able to detect CPV from fecal specimens in a rapid manner, provided that gel filtration of the samples through a spun column was done to remove inhibitory substances from the fecal specimens. These results suggest that the PCR assay can detect the presence of CPV in dogs early enough to prevent secondary infection by CPV in veterinary hospitals. PMID- 7785191 TI - Antibioresistance of Escherichia coli strains isolated in Morocco from chickens with colibacillosis. AB - Two hundred and fifty eight isolates of Escherichia coli were made from autopsied chickens showing lesions of avian colibacillosis. Antibiograms showed high levels of resistance (greater than 40%) to sulphonamides (SSS), oxytetracycline (OT), trimethoprim + sulphamethoxazole (STX) and chloramphenicol (C). Medium frequencies of resistances (from 15 to 40%) were noted for streptomycin (S), spectinomycin (SPT), nalidixic acid (NA), oxolinic acid (OA), flumequine (UB) and enrofloxacine (ENR). For ampicillin (AM), gentamicin (GM), nitrofurans (FT), colistin (CS) and rifampin (RA) the frequencies of resistance were low (less than 15%). A linked resistance was observed for the 4 quinolones. A significant percentage of isolates (82.5%) were resistant to at least 2 antimicrobial agents. The most frequent antibiotypes were: C.OT.SSS.STX (4.65%), C.OT.SSS.STX.OA.NA.UB.ENR (4.65%), AM.S.C.OT.SSS.STX (4.26%) and OT.SSS.STX (3.87%). PMID- 7785193 TI - [Comparative evaluation of subtotal irradiation and polychemotherapy in the treatment of patients with lymphogranulomatosis]. AB - Subtotal irradiation after a method developed at the Central Research Roentgeno Radiological Institute in St.-Petersburg was used as the first stage of antitumor treatment in 15 patients with Hodgkin's disease. In another group of 15 patients with the same disease antitumor treatment was started with a cycle of polychemotherapy. Comparison of the two types of total-system cytostatic therapy demonstrated their similar antitumor efficacy as far as the immediate results were concerned, but it also showed a higher hematologic toxicity of subtotal irradiation vs. polychemotheapy. Possibility of assessing the total dose of cytostatic exposure in multiple-modality treatment (chemoradiotherapy) is discussed. PMID- 7785192 TI - [Clinical, radiologic and morphologic characteristics of localized forms of pulmonary tuberculosis. Tuberculosis and hypoplasia]. AB - Clinical and x-ray examinations and study of operation material from 555 patients with local forms of tuberculosis permitted the authors to distinguish three form of the condition: tuberculoma (77% of cases), cavitary (cavernous) tuberculosis (16%), and tuberculosis of the bronchi (5%). Morphologic investigations showed the local tuberculosis develops at small sites of pulmonary tissue hypoplasia. Sites of hypoplasia are usually concentrated in the pulmonary segments which are formed in the postnatal period, thus explaining the typical localization of a postprimary tuberculous focus. Tissue decomposition with development of destruction cavities is not characteristic of local tuberculosis. Cavitary (cavernous) form is a morphologic reflection of a tuberculous inflammation in the zone of cestous hypoplasia. Morphonesis of local forms of tuberculosis reflects its social dependence. PMID- 7785194 TI - [Use of magnevist in the clinical practice (clinical trials]. PMID- 7785195 TI - [Radiologic diagnosis of inflammatory complications of colonic diverticulosis]. AB - The authors analyze x-ray findings in 194 patients with colonic diverticulosis and its inflammatory complications. Clinical, x-ray, and morphologic studies helped the authors to specify the x-ray semeiotics of diverticulitis, paraintestinal infiltrates, intestinal fistulas. An optimal complex of radiological methods to detect each of these complications has been developed. The authors claim that irrigoscopy supplemented, if necessary, with simultaneous fistulography, or oral enterography is the priority and basic method for the diagnosis of inflammatory complications of colonic diverticulosis. PMID- 7785196 TI - [Radiologic endoscopy of the biliary system in cholelithiasis]. AB - Roentgenoendoscopic interventions combining diagnostic and therapeutic procedures were carried out in 320 patients with various pancreatobiliary diseases. Different combinations of therapeutic roentgenoendovascular interventions on the biliferous system are shown, which were used in 102 patients with clolelithiasis. These interventions were found a highly effective method for preoperative treatment and therapy of patients with cholelithiasis. Roentgenoendovascular interventions in cholelithiasis are conductive to optimization of surgical treatment. PMID- 7785197 TI - [Clinical and radiologic diagnosis of etiology of macrohematuria from urinary tract]. AB - Clinical, laboratory, ultrasonic, X-ray, and endoscopic methods were used to specify the cause of macrohematuria from the urinary tract at all levels. Seventy two patients with macrohematuria were examined; in 37 the process was localizes in the urinary tract (pelvic tumors in 2, calculi in 14, bladder tumors in 9, hemorrhagic cystitis in 2, cystic diverticuli in 3, tuberculosis in 1, prostatic adenoma in 2, prostatic cancer in 4, cases). An ultrasonic examination, though a valuable method, failed to detect papillary tumors of the pelvis when used alone. Transabdominal and transrectal ultrasonic examinations are sufficient to diagnose calculi, diverticuli, or cancer of the bladder, and the advantages of computer aided tomography over ultrasonic examination in the diagnosis of bladder carcinoma are doubtful. Examination of the prostate by transabdominal and transrectal ultrasonic methods helps to assess its true size and shape, detect changes in these parameters both in prostatitis and in tumors, including metastases of the tumor into adjacent organs and tissues. The problem of recognizing metastases of cancer of the bladder and prostate, when computer-aided tomography and magnetic imaging are of no avail for today, is still to be solved. PMID- 7785198 TI - [Radiographic evaluation of the clinical course and outcome in acute pneumonias]. AB - The authors review the data of x-ray functional examinations of 525 patients with acute parenchymatoys pneumonia, 393 convalescents after pneumonia 3-6 months after the disease and analyze 480 case histories of patients, hospitalized for acute pneumonia 10 years ago. Development, x-ray picture, and resolution of the process are described. Besides traditional x-ray examination, roentgenography in oblique projections and pulmonary sonography are recommended in order to specify the anatomic changes in the lungs. Functional peculiarities of the involved and intact lungs were studied. Altogether 92.4% of convalescents are discharged from hospital with changed pulmonary pattern and, rather often, with infiltration of the parenchyma in the subpieural portions of the involved lobes and segments, as well as with disordered respiratory function of the lungs. Unfavorable outcomes in remote period after disease (pneumosclerosis, pneumocirrhosis, emphysema, chronic pneumonia) are observed mainly in subjects discharged from hospital before complete clinical cure. PMID- 7785199 TI - [Interventional radiology of chronic hemorrhoids]. AB - Basing on the concept of hemorrhoids from pathologically changed groups of cavernous bodies of submucous layer of rectal transitional zone, the author used for the first time selective dearterialization of hyperplastic cavernous bodies which were at the same time three internal hemorrhoidal nodes. The therapeutic method consisted in roentgenoendovascular catheterization of the superior hemorrhoidal artery and embolization of its distal branches delivering blood to the internal hemorrhoidal nodes. Results of roentgenoendovascular treatment of 34 patients suffering from chronic hemorrhoids are analyzed. The author emphasizes the advantages of roentgenoendovascular occlusion of the superior hemorrhoidal artery in comparison with traditional drug therapy and surgery. No recurrences were recorded over 24 months after the intervention. PMID- 7785200 TI - [Psychophysiological factors in radiodiagnosis]. PMID- 7785201 TI - [Radiologic equipment with reduced radiation dosage]. PMID- 7785202 TI - [Magnetic resonance tomography in the diagnosis of intramedullary tumors]. AB - The data of magnetic resonance imaging in 23 patients is hardly sufficient to characterize the histologic types of intramedullary tumors. However, the presence of cystous type of structure of intramedullary tumors on magnetic tomograms with nonhomogeneous (iso- or hypointensive) signal on T1-suspended tomograms or of hyper- or hypointensive signal on T2-suspended ones is to a great measure indicative of infiltration and diffuse growth of a tumor. A solid structure of intramedullary tumor with homogenous hyperintensive signals on both T1- and T2 dependent tomograms is more frequently indicative of a slowly growing tumor not involving the medulla, e.g. ependioma. PMID- 7785204 TI - [Radiologic evaluation of effectiveness of physical training in patients with myocardial infarction]. AB - The findings of two-projection large-image fluorography of the thorax of 134 men aged 32 to 60 with a history of myocardial infarction are presented. Physical rehabilitation of these patients was either traditional (controls) or enhanced by physical training (test group). X-Ray characteristics of the pulmonary vascular bed help to detect left ventricular insufficiency even in cases when there are no clinical symptoms of it. Time course of X-ray and cardiometrical data helps not only to assess the efficacy of training, but permits detection of the progress of left ventricular insufficiency as well. Cardiometrical parameters (volume of the heart, left ventricular coefficient, hvs index, right-atrial coefficient) may be used to predict the course of coronary heart disease in the postinfarction period. PMID- 7785203 TI - [Transcutaneous transvenous occlusion of patent ductus arteriosus]. AB - Transvenous closure is described of the patent ductus arteriosus with a conical device that consists of polyurethane foam mounted on a stainless steel flame. Since 1981, the procedure has been performed in 273 patients in Russia. Permanent complete ductus closure was achieved in 258 (95%) patients. In eight cases (3%), the occlusion was incomplete. Complications occurred in 10 patients (4%), seven of whom required emergency surgery. The new technique combines certain advantages of both alternative methods. The conical shape of the occlusion device is well suited for the anatomic structure of the ductus. The possibility of selecting the size of the device permits reduction in the rate of incomplete closure while still taking advantage of transvenous delivery to avoid entryside problems. In the initial 10 years of experience, the described technique proved effective, safe, and applicable in the vast majority of patients older than 2 years. PMID- 7785205 TI - [Radiologic evaluation of the invasiveness of obliterative esophageal tumors]. AB - An original method of double contrast staining of the esophagus performed at the height of Muller's test has been developed and tried in 170 patients with obturating cancer of the esophagus. The composition and preparation of the mixture used is described, as well as the steps of the technique. The advantages of the new method in comparison with routine double contrast staining are demonstrated, for the extent of cancerous process in the caudal direction was accurately determined in each case. The authors recommend their method for surgical clinics and radiological departments to be used for determining the scope of surgical intervention and specifying the topometry before radiotherapy. PMID- 7785206 TI - [Combination of mandibular fibromyxoma and fibrous dysplasia of cranial bones]. PMID- 7785207 TI - [Differential diagnosis of benign spinal neoplasms]. AB - The authors analyze problems arising in differential diagnosis of benign spinal tumors not adequately described in available literature. The most characteristic x-ray symptoms of rare spinal tumors are presented. Methods of radiologic investigation such as polipositional roentgenography, tomography, roentgenography with direct image amplification are described in detail. A total of 102 observations of benign spinal tumors are analyzed: osteoblaclastomas responsible for 14.7% of osteoblastoclastomas, angiomas responsible for 66.7% of cases, osteochondroma occurring in 6.7% of cases, chordomas and osteoid ostema occurring in 10.7 and 1.0% of cases, respectively. PMID- 7785208 TI - [Advocating radiotherapy of non-neoplastic diseases]. AB - The authors a sum of the principal proofs, phenomena and facts that confirm the high efficacy of radiotherapy in acute and chronic inflammatory processes, degenerative dystrophic and hyperplastic diseases. The authors analyze the causes responsible for the unjustified rejection of the method in practical medicine and prove its efficacy in therapy of nontumorous diseases. PMID- 7785209 TI - [Gd-DTPA in the diagnosis of brain metastasis]. AB - The potentialities of present-day methods of imaging (computer-aided and magnetic resonance tomography) in the diagnosis of metastatic involvement of the brain are discussed. Besides routine scanning, the authors assess the efficacy of a contrast agent Gd-DTPA (Magnevist, Schering AG, Germany) used in magnetic imaging. The potentialities of reinforced-aided tomography, 0.04 and 1.0 Tesla magnetic imaging are compared on the basis of 23 cases. The results indicate that magnetic imaging at low-intensity magnetic field is approximately as effective as computer-aided tomography in the assessment of metastatic involvement of the brain; contrast reinforcement with Gd-DTPA appreciably improves the informative value of the method in comparison with reinforced computer-aided tomography. As for 1.0 Tesla magnetic imaging, it is highly informative and accurate in assessment of the type (single or multiple) of the pathologic process. Extra contrast staining with Gd-DTPA makes magnetic imaging still more reliable and superior to computer-aided tomography and 0.04 T magnetic imaging in the diagnosis of metastatic involvement of the brain. In this investigation authors performed analysis of 23 observations with metastases (22 cases were hystological verified) and estimated possibilities of modern diagnostic methods such as CT (+CM), standard MR imaging and MRI with Gd-DTPA (Magnevist, Schering AG, Germany). Authors have noticed that MR imaging with contrast enhancement is more efficient in diagnosis of brain metastases in comparison with CT. Metastases showed the signal intensity increase after Gd-DTPA injection. Small tumors and nodi situated nearly skull base and in cerebellum were more distinguished on MR imaging with contrast enhancement than before it. PMID- 7785210 TI - [Diagnosis of kidney tumors invading the vascular pedicle and inferior vena cava]. PMID- 7785211 TI - [The use of halotherapy for the rehabilitation of patients with acute bronchitis and a protracted and recurrent course]. AB - Halotherapy was used for rehabilitation in 25 patients with acute bronchitis of long-standing and recurrent types. The main therapeutic action was ensured by aerodispersed medium saturated with dry highly dispersed sodium chloride aerosol, the required mass concentration being maintained in the range of 1 to 5 mg/m3. Therapy efficacy was controlled through assessment of clinical, functional, immunological and microbiological findings. Metabolic activity values were taken into consideration as well. Positive dynamics of the function indices in the clinical picture resulted from elimination of pathogenic agents, control of slowly running inflammatory lesions and stimulation of some immune system factors. Favourable changes in metabolic activity were present: normalization of serotonin excretion, marked decrease of unbalance in lipid peroxidation antioxidant system. PMID- 7785213 TI - [Physical factors in the rehabilitative treatment of patients who have undergone operations on the fallopian tubes]. AB - Treatment results assessed in 170 females of the reproductive age who had previously undergone reconstructive-plastic operations on uterine tubes provide evidence for effectiveness of differentiated use of impulse infrared laser and sinusoidal modulated currents in combination with balneotherapy. The above physiotherapeutic modalities are considered good aftertreatment for females operated on the uterine tubes. PMID- 7785212 TI - [The treatment of patients with a disordered menstrual function by the transcerebral action of an ultrahigh-frequency electrical field]. AB - Transcerebral exposure to 27.12 MHz electric field was used in 100 females of reproductive age with menstrual dysfunction because of neuroendocrine syndrome. The treatment proved highly effective in menstrual disorders of central genesis this making it a treatment of choice in combined therapy of the above patients. PMID- 7785214 TI - [The use of low-temperature pelotherapy in the treatment of patients with rheumatoid arthritis (II)]. AB - Low-temperature peloids (t = +13, +14, +15 degrees C) application in rheumatoid arthritis patients produces local antiinflammatory, analgetic actions, suppresses immunocompetent system, improves locomotor functions. The above balneotherapy is indicated for patients with articular seropositive or seronegative RA irrespective of its activity in the presence of exudative-proliferative manifestations in the affected joints. In articular-visceral RA it is better to apply peloids in minimal activity of the inflammation. PMID- 7785215 TI - [Changes in the lipid peroxidation indices during the sanatorium-health resort treatment of patients with joint diseases, victims in the accident at the Chernobyl Atomic Electric Power Station]. AB - Joint degeneration and dystrophy observed in some subjects exposed to low-dose radiation after the Chernobyl accident is accompanied with more active production of lipid peroxidation products. This overproduction is corrected by combined sulfurated hydrogen balneotherapy and magnetophoresis of vitamin E on the affected joints. PMID- 7785216 TI - [Therapeutic physical exercise for patients after the amputation of the lower extremities at the sanatorium stage of rehabilitation]. AB - The authors propose a set of therapeutic exercises developed to prevent degenerative-dystrophic processes and to improve locomotor function in patients undergoing sanatorium treatment after lower limb amputation. Swimming and loading exercises have improved strength and performance of spinal muscles, amputated and supporting limb, reduced osteoporosis of the stump bone fragment. The efficacy of the above approach was evaluated by dynamometry on the test-dynamometer Biodex and by ultrasound osteometry. PMID- 7785217 TI - [The rehabilitation of patients with secondary (radiation) injuries to the brachial plexus]. AB - A close control is needed over large nerve trunks and plexuses in the course of their area radiation in cancer patients to prevent radiation damage to peripheral nervous system. Rehabilitation of patients with radiation-induced plexitis and neuritis urges early diagnosis and treatment as essential conditions for adequate recovery of the limb function. Diagnosis of radiation damage to peripheral nervous system should rest on clinical electrophysiological findings defining the degree of the nerve fiber injury and predict treatment outcomes. PMID- 7785218 TI - [Experience in treating patients with lymphedema using radon baths combined with local barotherapy at Belokurikha health resort]. AB - The efficacy of thermal nitrogen-radon water and local pneumocompression was studied in 66 patients with lymphedema of the lower limbs stage I-II receiving treatment in Belokurikha resort. The response of 10-48-month duration was achieved in 63 (95.5%) of those treated. The course of radon baths only was less effective. PMID- 7785220 TI - [A comparative evaluation of the results of using different means for stone expelling therapy in urolithiasis]. AB - A conventional approach to urolith elimination involving spasmolytics, water loading, terpene-containing drugs warrants efficacy in 80% of the cases. Diuretic tea promoted the stones evacuation from the ureter in 88.5%. Sinusoidal modulated currents with inductothermia and sound stimulation of the upper urinary tracts resulted in the stones elimination in 88 and 85.7% of the cases, respectively. A new method of urolithiasis treatment is suggested, tried and patented. It implies introduction of upper urinary tract sound stimulation with the frequency 2.4-3.3 kHz at the height of urinative effect of the tea. The resultant elimination of uroliths occurred in 129 of 134 patients treated (96.3%). The treatment is feasible both in inpatient and outpatient settings. PMID- 7785219 TI - [The stress-limiting action of pulsed infrared laser radiation]. AB - Experiments were carried out on male rats to study molecular background of stress limiting effect of impulse infrared laser radiation (0.89 mu). The motor cortex was subjected to 4.8 W local impulse laser radiation with an impulse length 10( 8) sec, 3000 Hz base frequency and 10 Hz modulating frequency during 10 minutes. The following data were estimated: DNA synthesis in the cells of the cortex, skeletal muscles and thymus recorded by 3H-thymidine inclusion in nuclear DNA, 11 OCS content in blood plasma. It was revealed that IR radiation stimulated DNA synthesis in all the examined tissues of intact animals and animals after proactive physical load (swimming). The preliminary laser radiation was an effective stress-limiting factor for the cortex and thymocytes of swimming rats, but did not prevent decreasing 3H-thymidine inclusion in muscles' nuclear DNA initiated by swimming. PMID- 7785221 TI - [The health resort as a center for propagandizing social health]. PMID- 7785222 TI - [The efficacy of the internal use of Slavyanovsk mineral water and a pectin extract in the combined health resort treatment of children exposed to radiation action]. PMID- 7785224 TI - [Regional hemodynamic indices as a criterion of the efficacy of massage effects]. PMID- 7785223 TI - [The effect of the types of balneo- and physiotherapeutic treatment on nickel and cobalt elimination from the body]. PMID- 7785226 TI - [The 80th anniversary of the I. M. Sechenov Crimean Republic Research Institute]. PMID- 7785225 TI - [The primary prevention of osteopenia]. PMID- 7785227 TI - [The 75th anniversary of the State Research Institute of Health Resort Science in Pyatigorsk]. PMID- 7785228 TI - [The 150th anniversary of Krainka health resort]. PMID- 7785229 TI - [The effect of different types of laser therapy on the reactivity of the peripheral blood neutrophils in patients with ischemic heart disease]. AB - The responses to laser therapy (intravenous, continuous skin exposure without a magnet, magnetic laser therapy) of 83 patients with coronary heart disease aged 50-80 demonstrated the advantages of noninvasive laser irradiation of blood. Myeloperoxidase activity may serve a criterion for estimating the number of irradiation procedures needed. PMID- 7785230 TI - [The terrain cure under moderate altitude hypoxia in the combined sanatorium health resort treatment of patients with ischemic heart disease after aortocoronary bypass]. AB - Muscular exercise in the form of terrain walking proved to be a useful component of combined conditioning of coronary heart disease patients after aortocoronary shunt functional class 1 and 2. In conditions of moderate altitude resort such training mobilizes cardiovascular reserves of CHD patients. The outcome of the above sanatorium rehabilitation depends largely on contractility of left ventricular myocardium. PMID- 7785232 TI - [Macrosomia and prognosis in cancer patients]. PMID- 7785233 TI - [Photodynamic therapy for malignant tumors]. PMID- 7785231 TI - [The effect of cold exposure on the respiratory function in children suffering from inflammatory lung diseases]. AB - Single total (air bath, douche) and local (cooling of the feet with water) exposure to mild cold do not arise noticeable disorders of the respiration function in children suffering from recurrent and asthmatic bronchitis in remission. Local cold procedures improve bronchial patency while the exposure to heat results in its worsening. PMID- 7785234 TI - [Molecular mechanisms of estradiol-dependent tumor growth]. PMID- 7785235 TI - [Breast cancer morbidity in Dagestan]. PMID- 7785236 TI - [Biochemical parameters in the comprehensive diagnosis of lung cancer]. AB - Biochemical characteristics of blood serum were studied in 310 patients with lung cancer (stage I-IV), 188 cases of non-malignant pathology od the lung and 35 healthy subjects. Mean levels of total sialic acids, lipid-bound sialic acids, neuron-specific enolase and lactate depydrogenase in blood serum of cancer patients were significantly higher than those in control groups. Mean neuron specific enolase concentrations in small cell carcinoma of the lung were significantly higher than those in squamous cell and glandular carcinoma and carcinoid. Significant differences were observed for blood serum levels in cases of lung cancer disseminated to the liver and bones, as compared with those without distant metastases. Gamma-glutamyl transferase proced the most sensitive and specific when used for diagnosis of hepatic metastases, while alkaline phospohase--for bone metastases. PMID- 7785237 TI - [Diagnostic value of investigating exhaled air condensate in lung cancer]. AB - Parameters of lipid peroxidation and the levels of calcium ions in blood plasma and exhaled air condensate (EAC) were studied in 47 patients with lung cancer. The changes in EAC turned out to be more specific than those of blood plasma. The level of lipoperoxidation in condensate in cancer patients was lower than in healthy subjects. However, calcium cations concentrations in both blood and EAC were relatively higher, the latter difference being significant. The investigation pointed to a greater diagnostic value of EAC measurements, as compared with blood plasma, in lung cancer patients. PMID- 7785238 TI - [Evaluation of radiation and non-radiation factors in the development of lung cancer in radiochemical plant employees]. AB - Five hundred workers of a nuclear facility (162 cases of lung cancer and 338 healthy subjects) were examined on a case-control basis using the logical regression method and 10 radiation and non-radiation factors. Five significant factors were identified. The following rick values were obtained for them: tobacco smoking-6.6; plutonium-associated pneumosclerosis-4.6; plutonium incorporation-3.1; chronic non-specific diseases of the lung-2.1 and gamma ray exposure-1.6. Radiation-associated rick was under 25%, while that of non radiation factors not less than 70%. PMID- 7785239 TI - [Prostaglandins E in malignant stomach neoplasms]. AB - Prostaglandins E (PGE) levels in gastric neoplasme have been studied radioimmunologically in 84 patients (aged 31-77) with tumors of different stages. A relationship between PGE level and main clinico-morphological features of tumor has been established. PGE concentration was shown to correlate with age, stage, histological pattern of tumor, cell differentiation and tumor infiltration. The highest PGE concentrations were observed in young patients, low-differentiated adenocarcino, a and pronounced tumor infiltration to adjacent tissues. No correlation has been found between PGE level and sex and tumor localization and size. The PGE level in the intact gastric mucosa was significantly lower in the body of the stomach than in its proximal and upper parts. The results of the investigation suggest a possible use of PGE antagonists for stomach cancer treatment. PMID- 7785240 TI - [Lactate dehydrogenase isozyme profile in gastric mucosa as an early marker of possible neoplastic pathology in children with chronic gastroduodenal diseases]. AB - The lactate dehydrogenase (LDH) isoenzyme profile was studied in bioptic samples of gastric mucosa taken from 57 infantile patients suffering from chronic gastroduodenal pathology and 7 children with gastric functional disorders. The investigation showed LDH1 level to decrease and that of LDH5 to increase, the LDH5/LDH1 ratio increasing accordingly, in cases of erosive gastro-like gastroduodenitis and duodenal ulcers. The degree of said changes was found to correlate with the extent of morphological lesions of gastric mucosa and the most pronounced changes were recorded in cases of gastric mucosa gland atrophy. Similar changes in LDH isoenzyme profile had been identified in patients with gastric tumors. Said findings may be used in identification of groups at high risk for gastric carcinoma. PMID- 7785241 TI - [Evaluation of tumor necrosis factor (TNF) in cancer patients]. AB - The levels of TNF spontaneously produced in monocyte and macrophage supernatants were measured in 65 patients with tumors of different localization and stages. The TNF levels in blood monocyte and macrophage supernatants obtained from peritoneal washings were found to significantly differ from those in blood serum in the same patients. The highest TNF concentrations were registered in monocytes supernatants sampled from rectal and breast cancer patients. A relationship between cancer cachexia and TNF level is discussed. PMID- 7785242 TI - [Distribution of alleles of DRB, DQB and DQA loci of major histocompatibility complex in healthy donors of Saint Peterburg]. AB - The distribution of alleles of DRB, DQB and DQA loci was investigated in 118 healthy donors from St. Petersburg. Said alleles were identified by the restriction fragment length polymorphism method using DRB, DQB and DQA probes after TaqI digestion and Southern blotting. The frequencies of said alleles were compared with those of a cohort of healthy donors living in Germany. A significantly higher frequency of DRB-17-2 was identified in the Russian donors, as compared with the German counterparts. Also, the Russian donors revealed a decrease in the frequency of DQB-1 (P = 0.01) and an increase in that of DQB-X allele (P = 0.05). An analysis of DRB, DQB and DQA locus a alleles adhesion in a sample of donors from St. Petersburg showed it to agree, in a large proportion of cases, with the literature data. A parallel study of immunological specificity of DR antigen was undertaken to compare the results of genetic and serologic typing; errors in DR specificity identification were found to have been made in 17.0%. PMID- 7785243 TI - [Intrathecal synthesis of immunoglobulins G in patients with nervous system neoplasms]. AB - Brain tumor development and their recurrence are accompanied by an increase in IgG levels in liquor as well as in the number of circulating immunocomplexes and by the presence of blockage factors in liquor. The data presented in the paper, on the whole, illustrate the development of autoimmune reactions, which happen to be mechanisms involved in the pathogenesis of brain tumor growth and recurrence. Surgical removal of tumor is followed by a reduction in the rates of IgG synthesis. PMID- 7785245 TI - [Functional status of mast cells in subcutaneous connective tissue of rats with lymphosarcoma of Pliss]. AB - The functional status of a population of mast cells taken from the subcutaneous connective tissue of rats with lymphosarcoma of Pliss and those suffering from aseptic inflammation was evaluated. The experiment established such manifestations of remote influence on the mast cell population, at early stages of tumorigenesis, as faster rates of tumor growth and mast cells maturation and enhanced degranulation. Initial signs of functional exhaustion of the mast cells population was seen as a paraneoplastic syndrome. PMID- 7785244 TI - [Leukemia in delta-GAG-MYC transgenic mice]. AB - Transgenic mice carrying two delta-gag-myc genetic constructions were produced and kept under observation during their whole life. Nineteen out of 119 transgenic mice developed such hemopoietic diseases as lymphoid tissue hyperplasia, lymphoma, lymphosarcoma and myeloma. Lymphoid tissue hyperplasia and lymphoma generally involved multiple hyperplastic and neoplastic pathologies which were regarded, on the whole, as "malignant disease". In all cases, lymphosarcoma and myeloma were the only deadly pathologies. Lymphomas and myelomas were detected after 3-9 months, lymphosarcomas--18-29 months while lymphoid tissue hyperplasia occurred virtually throughout the entire life span--3 31 months. The study has shown that transgenic mice carrying delta-gag-myc gene in their genome can be used in the designing of special models for investigations of certain patterns of leukemia. PMID- 7785247 TI - [Criteria for evaluation of non-specific anti-tumor resistance]. AB - Non-specific antitumor resistance levels have been measured by correlation regression analysis on the basis of 33 parameters in rats with tumors and under the influence of Thio-TEPA treatment, endolymphatic administration included. The study established 16 highly-informative criteria and parameter a, an integral indicator for non-specific antitumor resistance evaluation, which describes the synthetic activity of peripheral blood lymphocytes. PMID- 7785246 TI - [Coordination of lymphocytic enzymes of the rat thymus gland in experimental chemotherapy]. AB - The report deals with an investigation of the relationship between thymal cortical lymphocytes metabolism and antitumor response in Wistar rats with ovarian tumors, injected with Thio-TEPA intramuscularly and endolymphatically. Antitumor response and enzymatic indexes coordination appeared to be higher with the latter route. PMID- 7785248 TI - [Groups at high risk for skin cancer]. AB - A special program aimed at detecting skin cancer at early stages was worked out and launched into use in 1989. It provides for a series of measures for primary examination and subsequent follow-up of population. Dermatologists conducted examinations of persons at high risk 2-4 times a year depending on the disease. They were joined by oncologists, whenever required, and morphological examinations were sometimes carried out. The group at high risk for skin cancer included patients older than 50, with the following pathologies: (I) Obligate precancerous dermatites: Bowen's syndrome, erythroplasia of Queyrat, Paget's disease (extramammary localization), intraepidermal epithelioma of Jadassohn, late-onset radiation dermatitis, early childhood-Kaposi's disease, Manganotti's chilitis and verrucous precancer of the lip; Optional precancerous dermatosis: childhood-onset epidermodysplasia veruciformis, actinic keratosis, cutaneous horn, keratoacanthoma, carcinoid papillomatosis of Gottron, giant condyloma of Buschke-Lowenstein, leukoplakia and limited precancerous hyperkeratosis of the lip's red edge; (2) Dermatoses involving pathological regeneration: eruthematosis, lupus tuberculosis, psoriasis (more than 15 years old), trophic ulcers, extensive scars (particularly, those caused by burns), chronic ulcerative pyoderma and pyoderma vegetans; (3) Hemorrhagic diathesis on the surface or fundus of neoplasm; (4) Consolidation at neoplasm base; (5) Absence of complaints; (6) Resistance to therapy. PMID- 7785249 TI - [Diagnosis of cerebral meningioma before hospitalization]. AB - Clinical neurologic symptoms were evaluated in 300 cases of brain meningioma eersus tumor course. An attempt was made to assess difficulties involved and errors made in diagnosing tumors before admission to hospital. The study identified initial signs of the disease, symptom combinations as well as single symptoms considering their frequency and importance for cerebral meningioma diagnosis before admission. PMID- 7785251 TI - [Morbidity and mortality of malignant tumors in the population of a Moscow district]. AB - An epidemiologic study of malignant tumors was carried out in a cohort of population of a district in Moscow. The district is situated on the leeward side of a cluster of factories which discharge 270 cu tons of pollutants per year. Nine of the eleven apartment houses under study were put up in the 60-70 ies when the factories were in operation. The cohort included 1,095 males and females who had lived in that district at least 5 years until the start of the investigation. The tumor morbidity and mortality in this cohort were evaluated for the period of 1988-1992. Morbidity of virtually all known tumors and mortality proved to be in excess of all expectations. However, significant differences between the actual and expected levels were obtained in the total number of tumors, in females, only (actual number-24; expected number-13.76), and for breast tumors (7 and 2.82, respectively). PMID- 7785250 TI - [Use of navoban for nausea and vomiting caused by chemotherapy for malignant tumors]. AB - The antiemetogenic effect of navoban (Sandoz) was studied in 26 patients receiving chemotherapy, with application of platidiam in 22 cases included. No vomiting was registered. Nausea was observed in 9 cases within the first 24 hrs and a slight reduction in appetite--in 13 cases. Navoban proved one of the most potent antiemetics devoid of any untoward side-effects. PMID- 7785252 TI - [Combined multi-stage treatment of a patient with non-differentiated adenocarcinoma of the lungs with solitary brain metastasis]. PMID- 7785253 TI - [Representation of the dynamics of a neoplastic process]. PMID- 7785254 TI - Neurologic complications of lightning injuries. AB - Over the past ten years, we have cared for 13 patients who suffered serious neurologic complications after being struck by lightning. The spectrum of neurologic lesions includes the entire neuraxis from the cerebral hemispheres to the peripheral nerves. We describe these various neurologic disorders with regard to the site of the lesion, severity of the deficit, and the outcome. Damage to the nervous system can be a serious problem for patients struck by lightning. Fatalities are associated with hypoxic encephalopathy in patients who suffered cardiac arrests. Patients with spinal cord lesions are likely to have permanent sequelae and paralysis. New technology for detecting lightning with wideband magnetic direction finders is useful in establishing lightning-flash densities in each state. Florida and the Gulf Coast states have the highest densities. Colorado and the Rocky Mountain states have the next highest. PMID- 7785256 TI - Costs of minimally invasive laser surgery compared with transurethral electrocautery resection of the prostate. AB - We reviewed hospital charges for patients undergoing uncomplicated endoscopic surgical resection for symptomatic bladder outlet obstruction due to benign prostatic hyperplasia over a 1-year period at a single institution. Of 115 patients, 67 underwent transurethral electrocautery resection of the prostate, and 48 underwent endoscopic neodymium:yttrium-aluminum-garnet laser ablation of the prostate under direct vision. Analysis showed a cost differential between these 2 surgical treatments in excess of $2,000, favoring laser prostatectomy (P < .0001) over transurethral electrocautery resection. The single greatest difference between the treatments was the ability to manage all patients receiving laser treatment as outpatients, whereas the mean and median hospital stay after transurethral electrocautery resection was 3.0 days. Taking additional cost variables into account and decreasing the cost of laser delivery systems would further increase this cost differential in favor of laser therapy. The diminished postoperative morbidity associated with laser treatment also promises lower total costs over the long term. PMID- 7785255 TI - Immunopathologic effects of silicone breast implants. AB - Silicone-gel breast implants have been associated with a myriad of autoimmune and connective tissue disorders by anecdotal reports and small observational series. To date, no prospective epidemiologic studies have been done to substantiate these observations, but an increasing body of literature is being developed and older studies are being recognized that point to immunotoxic or inflammatory effects of these breast implant components. The development of disease due to implants would depend on the interaction of genetic host factors so that only a few patients would potentially be at risk. Based on the example of other chemically mediated disorders, such as scleroderma in association with silica exposure, latency periods of more than 30 years before disease develops may be possible. Herein we review studies on silicone and immunity. PMID- 7785257 TI - Glycemic control and complications of diabetes mellitus. PMID- 7785259 TI - Cervical pathology--the Bethesda System and the 'atypical squamous cells of undetermined significance' controversy. AB - The Council on Scientific Affairs of the California Medical Association presents the following epitomes of progress in pathology. Each item, in the judgment of a knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and clinical importance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of progress in medicine, whether in their own field of special interest or another. The epitomes included here were selected by the Advisory Panel to the Section on Pathology of the California Medical Association, and the summaries were prepared under the direction of Yutaka Kikkawa, MD, and the panel. PMID- 7785260 TI - Specimen quality and accuracy of fine-needle aspiration biopsies. PMID- 7785258 TI - Role of nitric oxide in insulin-dependent diabetes mellitus-related vascular complications. AB - Patients with insulin-dependent diabetes mellitus are at high risk for vascular disorders such as hypertension, nephropathy, and retinopathy. The most common cause of morbidity and mortality in patients with insulin-dependent diabetes is vascular disease. Despite ongoing research, the pathogenesis of vascular disease in diabetes remains unclear. In recent years, numerous investigators have examined the role of the endothelium-derived relaxing factor, nitric oxide, in the disease state of hypertension and its complications. We review the role of nitric oxide in the development of diabetes-related vascular disease and discuss findings suggesting that nitric oxide metabolism and vascular responsiveness to nitric oxide are altered in diabetes. Patients with diabetes may benefit from therapy that addresses this pathogenic deficiency. PMID- 7785261 TI - Molecular pathology and cancer genetic screening. PMID- 7785262 TI - Predisposition to thrombosis by a factor V mutation causing hereditary resistance to activated protein C. PMID- 7785263 TI - Microalbuminuria. PMID- 7785264 TI - 'Crystal' and pregnancy--methamphetamine-associated maternal deaths. PMID- 7785265 TI - Congenital malaria in a nonidentical twin. PMID- 7785266 TI - Cardiac rhabdomyoma with cardiac arrest. PMID- 7785267 TI - Lesbian health care. What a primary care physician needs to know. AB - Many primary care physicians take care of lesbians and women sexually active with women without being aware of their patients' sexual orientation. These women have unique medical and psychosocial needs that each physician must consider. Lesbian identity or being sexually active exclusively with women influences care in areas such as sexually transmitted diseases, risk of human immunodeficiency virus infection, counseling, cancer risk, screening, parenting, depression, alcohol use, and violence. We review an approach to taking a history with all women that facilitates open, comfortable communication with lesbians. We also review specific medical and psychosocial areas of primary care in which caring for lesbians is different from caring for other women. Further research is needed on lesbian health issues to provide appropriate guidelines to clinicians. PMID- 7785268 TI - Work-site health promotion programs and health care reform. PMID- 7785269 TI - Management of diabetes mellitus after the DCCT--what's next? PMID- 7785270 TI - Dietl's crisis revisited--the enigma of nephroptosis. PMID- 7785271 TI - Can specialists practice primary care? PMID- 7785272 TI - Guns and violence--a second opinion. PMID- 7785273 TI - Lead poisoning alert--false alarm? PMID- 7785274 TI - Gallium citrate Ga 67 scanning in acute renal failure. PMID- 7785276 TI - [Multifocal-motor neuropathy and motor neuropathy with multifocal conduction block (Lewis-Sumner syndrome)]. AB - Multifocal motor neuropathy, which mimics lower motor neuron disease, is a rare and curious demyelinating neuropathy characterised by slowly progressive, asymmetric limb weakness within the distribution of individual peripheral nerves, wasting, cramps, fasciculations and rare sensory involvement, but without upper motor neuron signs. The cardinal feature and primary pathophysiological basis for the weakness is the multifocal motor conduction block which remains stable for years at the same site and is confined to motor axons. It is defined as > 50% reduction in both the CMAP and the negative peak area on proximal stimulation, as compared with the distal stimulus response without any change in the negative peak duration. Nerves at the site of the conduction block show demyelination, endoneural edema, rudimentary onion bulbs and lymphocytic inflammation. Sensory nerves may show mild demyelination, axon loss and lymphocytic inflammation. The majority of patients shows elevated titers of anti-glycolipid antibodies, which may block the Na+ channels, produce demyelination or interfere with remyelination. However, their role in the pathogenesis of multifocal motor neuropathy remains uncertain. Multifocal motor neuropathy is regarded as the predominantly motor variant of chronic inflammatory demyelinating polyneuropathy and can be treated best with immunoglobulins and cyclophosphamide. PMID- 7785275 TI - [The interactions of antidepressant drugs]. AB - An overview is presented of interactions of currently frequently used antidepressants with various other drugs. The effects of interactions of tricyclic antidepressants, tetracyclics, monoamine oxidase (MAO) inhibitors, lithium and carbamazepine are comparatively well documented, their pharmcodynamic and pharmacokinetic characteristics extensively researched and well known to the practitioner. These interactions concern synergic effects, enzyme inhibition, enzyme induction in the liver, competitive inhibition of absorption and reciprocal effects on the receptor. With regard to lithium, problems of renal clearance and circulation are also important. On the other hand, interactions of reversible and selective MAO-A inhibitors (RI-MA) and selective serotonin reuptake inhibitors (SSRI) with various other drugs are in the process of elucidation. Very threatening interactions are known to be caused by a combination of SSRI and MAO inhibitors (serotonergic syndrome). SSRI and tricyclic antidepressants dispensed concurrently cause an increase in the plasma level of the tricyclic antidepressant. Hence, the practitioner must become aware of this high responsibility towards the patient when prescribing even on single drug, which must be selected with the utmost care. PMID- 7785277 TI - [Peripheral cranial nerve paralysis as a sequela of operations of the carotid artery]. AB - 265 carotid endarterectomies in 210 patients (all vein patch in the carotid bifurcation) were investigated postoperatively for the presence and reversibility of cranial nerve palsy especially for N. facialis, N. hypoglossus, and N. vagus paresis. Additionally, the anatomical relationship between the affected cranial nerve and the carotid artery and the influence of surgical case load on the incidence of cranial nerve paresis were investigated. Altogether 28 (10.5%) cranial nerve injuries were registered. In 6 (2.2%) cases the hypoglossus nerve was injured, in 13 (4.9%) the vagal nerve (N. laryngeus recurrens) and in 9 (3.4%) facial nerve paresis occurred. Cranial nerves VII and X, which are not directly connected with the area operated on, show significantly more injuries than the hypoglossal nerve (p < 0.01), which is located closer to the carotid artery. Significantly lower rates of cranial nerve injuries (p < 0.01) were recorded in cases operated on by surgeons with greater experience (> 30 cases) than by surgeons with a case load below this threshold. Although different reasons for cranial nerve injuries such as direct pressure, retraction or edema are known, all pareses show an excellent spontaneous recovery rate within the period of one year. PMID- 7785278 TI - [Comparative psychiatric diagnosis in dialysis patients and kidney transplant recipients]. AB - 12 male and 8 female patients treated by hemodialysis (mean age: 38.5 years, s = 11.1) and 10 male and 10 female renal transplant recipients (mean age: 35.4 years, s = 9.7) were given 8 psychological tests. The results of both groups were compared with each other and with the respective standardizations. RESULTS: In comparison with the respect standardizations the transplant recipients obtained average results in 5 to 6 achievement tests, whereas the dialysis patients showed deficiencies in higher perceptive processes, namely attentiveness, power of concentration, speed of performance, reductive thinking, and short-time memory. Confronted with problems which must be solved by making use of formerly acquired knowledge, experiences, and skills (crystallized intelligence), the average results of both groups coincided with the average of the respective standardizations. As for their way of acting in frustrating situations, the persons of both groups tried to avoid any aggressive reaction against fellow-men. They tended to self-reproaches, though generally referring to inevitable circumstances. If possible they evaded any question of guilt by minimizing the problems. All in all, renal transplantation can effect a substantial improvement in mental ability, especially of fluid intelligence. PMID- 7785279 TI - Chronic relapsing polyradiculoneuropathy in IgG lambda monoclonal gammopathy of undetermined significance (MGUS)--complete remission following carmustine treatment. AB - A previously healthy 43 year-old female developed IgG lambda monoclonal gammopathy of undetermined significance (MGUS) and ascending sensorimotor polyradiculoneuropathy which relapsed 11 times within 2 years. Marked improvement was noted repeatedly after plasmapheresis. However, on each occasion symptoms and signs of polyradiculoneuropathy recurred almost exactly 3 weeks after plasma pheresis. Following 6 weeks of treatment with carmustine (70 mg/week), nearly complete recovery was established, which has persisted up to now (82 months after the end of therapy). The close temporal correlation between clinical relapse and recurrence of the IgG paraprotein and its permanent absence in stable clinical remission after carmustine treatment suggest a causal relationship between the paraprotein and the polyradiculoneuropathy. However, further studies are required to confirm this observation, as well as the efficacy of carmustine therapy. PMID- 7785280 TI - [Microinvasive, CT-controlled periradicular therapy in treatment of chronic intervertebral disk-induced functional disorders]. AB - The disease of the spinal column is number 2 of common diseases world-wide and leads to high business- and commerce-related losses as well as to high expenses for the health care systems. An effective treatment of this disease is given by the microinvasive. CT controlled periradicular therapy (micro PRT). Under visibility, the tip of a canula is led directly and high precisely in close neighbourhood to the prolaps, then locally NaCl and cristaline cortisone (40 mg Volon A) is instillated. The periradicular distribution and the distribution into the epidural space is documented via contrast medium. A retrospective study with 220 patients and a prospective randomized double blind study with 40 patients (10 mg vs. 40 mg Volon A) were carried out. The average age of the retrospective collective was 53.1 +/- 12.4 years, average treatment period 18.4 weeks, and the mean follow-up 17 months. The mean value of successful treatment of lumbal spine was at 60% (spine 88.5%) with protrusion, with prolaps at 75% (spine 94%), with sequester at 94%, and with stenoses at 69% (spine 60%). With 78.8% of the patients, the percentual result was constantly good at the time of questionnaire as to the end of the treatment. 7.7% still took analgesics, 5.9% were post operated. 1.8% of the patients made a pension application. The average age of patients within the prospective randomized double-blind-study was 47.2 +/- 11.9 years. At 27.5% of the patients, the start of pain was about more than 5 years ago and goes back to about 23 years (72.5% had pain more than 1 year). The mean value of visits was 4 physicians per patient, and 5 months of follow-up. There is a high significant improvement in results within the group with 40 mg Volon A (p = 0.0351479). The entire improvement, subjectively estimated (visual analogical scale) within this group was at 90%. After end of therapy, 83.3% (n = 30) had stopped the taking of analgesics and the neurologic deficit decreased significantly. Furthermore, significant reduction of prolapses could be observed at 60% of the patients in both study groups (n = 156). The CT scopic micro PRT with 40 mg Volon A leads to a significant improvement of pain and neurologic symptoms caused by chronical disk herniation. PMID- 7785281 TI - [Unexpected fatalities of patients in medical treatment]. AB - Our results are based on 190 autopsy records of unexpectedly deceased patients in connection with medical treatment between 1984 and 1993. 161 times autopsy has been ordered by the local Public Health Office to establish cause of death. In 5 of these cases indications of medical maltreatment were found and the cases had been brought to trial. Inspite of suspected problems with medical treatment the treating doctors certified natural death in 8 of these cases and autopsies were carried out by general pathologists. Secundarily these cases were brought to court and corpses were reexamined by forensic pathologists. 29 times autopsy has been ordered by court from the beginning. 102 patients (53.7%) died during medical treatment ("mors in tabula"), while 88 patients (46.3%) died within days or weeks after treatment. 135 fatal incidents occurred in surgery, 13 cases during diagnostic procedures or puncturing veins, 5 cases after drug administration, 5 cases during attempts at resuscitation, and 8 fatal cases during other special treatment. 11 times no medical treatment has been started (omission). Legal consequences of 42 cases done by court were: no accusation in 48%, only accusation and cessation in 26%, condemnation in 21% and acquittal in 5%. PMID- 7785282 TI - [A case of patient homicide]. AB - The phenomenon of patient homicides committed by health service employees has, in the previous years, repeatedly aroused much attention. The cases made known in Germany, the USA, Holland, Norway, and Austria appear to provide evidence to the effect that we are not only dealing with unique incidents. The scientific investigation of this especially sensitive taboo-topic is, to date, missing. The judicial trials carried out emphatically indicate that culprit motives, colleague behavior, but also to a large extent decisions made by superiors remain unclear. It remains controversial, what effect working conditions, strain of employees, their level of education and personal viewpoints over such criminal acts they possess. Finally, the long latency period between the first internal suspicions and the responsible parties' appropriate reactions requires duplicatable explanation. The following paper presents a German single-case study of patient homicide by a female nurse. The focus on causality rests on the presentation of developments up to the point where the long-fermenting suspicion could no longer be dismissed, and appropriate consequences took place. The account largely avoids the "definite" findings required during the judicial process. It concerns rather above all an open, uncertain, and possibly without external influence course of development which in stages each colleague in the health professions can trace, to the point where the uncertain and horrifying suspicion became a certainty. With this single-case study in hand it is made understandable in which ways personal circumstances and professional conditions at the worksituation can intertwine in such a way that the original motivation to help turns into its abysmal opposite. It is the author's intention to make preventive learning possible through this single case study. Every employee in the health professions should proceed on the assumption that such occurrences could also in his own field of work come to pass. In this respect, it is of considerable importance to differentiate between hasty and untenable incriminations and original increasing early-warning signs. PMID- 7785283 TI - [Bioprosthesis degeneration and reoperation in the aortic and mitral position]. AB - In agreement with our experiences from our first study 15 patients (8 men, 7 women) underwent reoperation because of degeneration of bioprosthetic valves implanted in aortic or mitral position during the last 24 months. At reoperation 4 patients had a more complex cardiac procedure (double valve replacement, double valve replacement with bypass grafting, valve replacement with enlargement of the valvular area). There was no acute operation and only 1 patient was serious symptomatic preoperatively (NYHA IV). We revealed a mean implantation time of 126.4 months +/- 32.2 (median 130) for all bioprostheses without a significant difference in implant time regarding to aortic or mitral position. At reoperation bypass time (p = 0.001) and aortic clamp time (p = 0.011) was significantly longer compared to the first operation. There was no perioperative death, all patients are still alive and in good condition (8 of them NYHA I, 7 NYHA II). The early change of tissue degenerated bioprostheses can be carried out under elective conditions with improved postoperative outcome: mortality and morbidity remains acceptable low. In our group incremental risk factors for early mortality are severely affected patients with low functional status (NYHA IV) and acute operation. Preoperative coronary angiography remains essential for evaluation of concomitant coronary artery disease. PMID- 7785286 TI - The gynecological manifestations of Crohn's disease. PMID- 7785287 TI - Cap on malpractice awards. PMID- 7785285 TI - Caring for the diabetic patient. PMID- 7785288 TI - An unusual sonographic appearance of a chronic renal peritransplant lymphocele. AB - Lymphoceles are the most common renal peritransplant collections. They typically develop and progress within 6 months of transplantation. Clinical presentation is varied and includes azotemia, lower extremity edema, fever, weight gain, tenderness over the allograft, palpable mass, and thromboembolic complications. Herein, we present a chronic peritransplant lymphocele with unusually thick and irregular internal septae which could easily be mistaken for other complex peritransplant or pelvic masses. In this case, color Doppler flow imaging helped to limit the differential diagnosis as well as to guide appropriate intervention. Additionally, we describe the pathophysiology of lymphocele formation and treatment options. PMID- 7785289 TI - The Wisconsin Diabetes Control Program: a health systems and community-based approach. AB - The Wisconsin Diabetes Control Program will address the health needs of people with diabetes by working closely with the Wisconsin Affiliate of the American Diabetes Association and other diabetes health professionals in the state. The 5 year program will use both health systems and community-based approaches to coordinate prevention, detection, and control activities required to reduce the burden of this chronic condition. This program represents a major shift in focus from previous diabetes control programs supported by the CDC, and is designed to establish the program as a key component of an evolving health care environment. PMID- 7785290 TI - A primary care perspective on "upgrading diabetes therapy" and NIDDM. PMID- 7785284 TI - [Expanded diagnostic possibilities for diagnosis and differential diagnosis of autoimmune hepatopathies using polymerase chain reaction (PCR)]. AB - This is a report on a case of autoimmunehepatopathy with misleading virus serology: A 34-year old female patient presented with abdominal signs of hepatopathy at Graz University School of Medicine. Hepatitis-C virus (HCV) serology was strongly positive indicating virus contact. The cellular activation was elevated, additionally increased ds-DNA-titer and mitochondrial antibody titres including the subfraction M2 were increased. In view of the differential diagnosis and therapeutic consequences molecular biology was used for additional information and a PCR carried out. The latter excluded infection with HCV confirming a false positive virus serology. The patient was treated with ursodesoxycholic acid, steroids and enzymes. She improved and showed no viral exposure. We conclude, that molecular biology represents an essential tool for the diagnosis of some selected critical cases of autoimmune-diseases such as autoimmune hepatopathy with false positive virus serology, if the underlying etiopathogenesis is not clear. PMID- 7785291 TI - Effects of a high protein intake on renal acid excretion in bodybuilders. AB - Bodybuilders often prefer a high protein diet to achieve maximum skeletal muscle hypertrophy. In this study the effect of a high protein diet on renal acid load and renal handling of proton excretion was studied comparing dietary intake and urinary ionograms in 37 male bodybuilders and 20 young male adults. Energy intake (+ 7%), protein intake (128 vs 88 g/d/1.73 m2), and renal net acid excretion (95 vs 64 mmol/d/1.73 m2) were higher in the bodybuilders than in the controls, however, urine-pH was only slightly lower (5.83 vs 6.12). In the bodybuilders renal ammonium excretion was higher at any given value of urine pH than in the controls. In a regression analysis protein intake proved to be an independent factor modulating the ratio between urine-pH and renal ammonium excretion. The concomitant increase of renal net acid excretion and maximum renal acid excretion capacity in periods of high protein intake appears to be a highly effective response of the kidney to a specific food intake leaving a large renal surplus capacity for an additional renal acid load. PMID- 7785292 TI - Olive oil- and sunflower oil-fried sardines in the prevention of rat hypercholesterolemia. AB - The effect of diets containing olive-oil-fried sardines (diet 1) or sunflower-oil fried sardines (diet 3) upon the serum cholesterol-raise induced by dietary cholesterol was studied after a 4-week experiment in growing Wistar rats. Results of diet 1 were compared to those obtained in diets containing casein plus olive oil (diet 2), whereas results of diet 3 were compared to those obtained with casein plus sunflower oil (diet 4). All diets contained cholesterol and bovine bile as a cholesterol-raising agent. The hypercholesterolemic effect of dietary cholesterol in fried-sardine groups (a total cholesterol (TC) increase of 0.9 mmol/L (p < 0.05 and 0.4 mmol/L (not significant) in groups 1 and 3, respectively) was markedly lower than in groups 2 and 4 (a TC increase of 13.9 mmol/L (p < 0.01) and 18.2 mmol/L (p < 0.01), respectively). Serum triglyceride levels decreased in fried-sardine diets (p < 0.05) while they increased in casein diets (p < 0.05). HDL-cholesterol levels appear lower in diet 1 than in diet 2 (p < 0.05), but similar in diets 3 and 4. However, HDL-fraction carries in diets 1, 2, 3 and 4, 13%, 4%, 53% and 5% of TC, respectively. Results showed that fried sardine diets exert a powerful check effect on the cholesterol-raising effect induced by dietary cholesterol. PMID- 7785293 TI - [Mealtime patterns in a southern German population. Results from the WHO MONICA 1984/1985 Augsburg nutritional survey project]. AB - Seven-day food records of the MONICA project Augsburg dietary survey, which were collected between October 1984 and May 1985 in 899 men aged 45-64 years (random sample), were used to analyze meal patterns. Among other variables, the emphasis was placed on meal frequency and rhythm, frequency of meal combinations, place and time of meal intake as well as on the contribution of different meals to selected nutrient intake. Breakfast delivers 17%, lunch 29%, and dinner 33% of the total daily energy intake; all other meals (snacks) deliver 21% of the energy intake. The mean contribution of the three major meals, such as breakfast, lunch and dinner to daily protein intake is 14%, 36%, and 36%; to fat intake 17%, 33%, and 35%, and to carbohydrate intake 23%, 25%, and 29%, respectively. Data on meal patterns are useful for the development of preventive strategies. PMID- 7785295 TI - Variation of trans fatty acids in milk fats. AB - Trans fatty acids are discussed in connection with an increased risk of atherosclerosis. Therefore, the development of a rapid and exact measuring method for the determination of trans fatty acids in milk fat is of great interest. Using gas chromatographic analysis of the trans-octadecenoic fatty acids as well as of the triglycerides of 100 different milk fat samples a formula consisting of different triglycerides for the quick determination of trans contents was developed by means of statistical methods (standard deviation = 0.293%, r = 0.9977). Subsequently, the seasonal variations of the trans contents in milk fat samples from a large milk collection area were determined using rapid triglyceride analyses. For the trans fatty acid contents of the 100 milk fat samples and the samples from the milk collection area scattering ranges of 1.91 6.34 wt% resp. 1.97-4.37 wt% were found; the mean contents were 3.83 and 3.18 wt%, and the median values 3.67 and 3.30 wt%, respectively. PMID- 7785296 TI - [Percutaneous mitral valvulotomy with the Inoue balloon in over 65-year-old patients--acute results and short-term follow-up in comparison with younger patients]. AB - Percutaneous balloon mitral valvulotomy (PBMV) with the Inoue-balloon is a proven therapy in young patients with mitral stenosis. In this study, we investigated primary results in PBMV of elderly patients. In 383 patients with mitral stenosis PBMV was done with the Inoue-balloon. We compared primary success rates and short term follow-up of 287 (74.9%) < 65-year-old patients and 96 (26.1%) > or = 65 year-old patients. Elderly patients were more likely to have atrial fibrillation (58% vs. 45%; p < 0.05), tricuspid regurgitation < or = II degrees (58% vs. 45%; p < 0.05), coronary artery disease (16% vs. 6%; p < 0.01), and previous pulmonary edema (42% vs. 30%; p < 0.05). PBMV was successful in 73.9% of the elderly and 84.7% of the younger patients (p < 0.05). Mitral valve gradients could be reduced from 12.5 +/- 11.6 mm Hg to 6.2 +/- 6.8 mmHg (p < 0.001) in elderly patients and from 15.5 +/- 6.9 mm Hg to 7.0 +/- 3.2 mm Hg (p < 0.001) in younger patients. Mitral valve areas increased from 1.0 +/- 0.3 cm2 to 1.6 +/- 0.5 cm2 (p < 0.001) in elderly patients and from 1.0 +/- 0.3 cm2 to 1.7 +/- 0.4 cm2 (p < 0.001) in younger patients. No patient died during the procedure. Two younger patients had emergency surgery because of pericardial tamponade following transseptal puncture. After PBMV elderly patients had more often an increase of mitral regurgitation (47% vs. 35%; p < 0.05) without need of an emergency mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785294 TI - [Improved microbiological assay of heterocyclic aromatic amines in cooked food]. AB - Heating of protein, especially muscle meat and meat extracts, can result in the formation of heterocyclic aromatic amines (HA) which are carcinogenic in animals. They are therefore unwelcome in human food. Here, an improved method for the microbiological assay of HA is reported; it makes use of the high mutagenic potency of HA in the Ames test and of the new Salmonella typhimurium strain YG1024 instead of strain TA98. The high sensitivity of the new strain is a consequence of its high acetyltransferase activity which results in a more efficient formation of genotoxic HA metabolites. The mutagenic activity of three selected HA in YG1024 is 10-20 times higher than that in TA98. This method can be used for the analysis of the HA content of food. A study of meat patties revealed significant differences in the mutagenic activity in the center and crust and of home-made and commercial patties; in both, the mutagenic activity was localized in the crust. PMID- 7785298 TI - [Dynamic obstruction of the left ventricular outflow tract by prosthesis dysfunction]. AB - We report on a case of dynamic left ventricular (LV) outflow tract obstruction combined with a prosthetic valve dysfunction 13 years following mitral valve replacement with a Hancock bioprosthesis in a 46-year-old patient. Previously, repeated echocardiographic controls had been performed at regular intervals and the prosthesis had been found to be oversized and seated in abnormal position, with projection of the struts into the LV outflow tract. Moreover, a mild chronic LV outflow tract obstruction had been diagnosed upon intermittent findings of relatively high velocity in the outflow tract. Clinically, however, the patient had been stable and the function of the prosthesis had been good. With the onset of the mitral regurgitation due to prosthesis failure, a dynamic obstruction to LV outflow occurred, with severe narrowing of the LV outflow tract by a strut of the bioprosthesis during systole. Subsequently, a low cardiac output syndrome developed. The patient was referred for a mitral valve reoperation. The valve was replaced with a Sorin Bileaflet Carbon prosthesis. On the setting of a mild chronic LV outflow obstruction due to the oversized prosthesis and its abnormal position, hypercontractile cardiac function as a result of mitral regurgitation may have caused the dynamic and symptomatic LV outflow tract obstruction. PMID- 7785297 TI - [Results of valve-sparing correction of aortic valve insufficiency]. AB - The risk of valve-related complications and the necessity of anticoagulation in patients with prosthetic valves, has led to new operative techniques in the correction of severe aortic insufficiency. In the last 2 years, 35 patients (mean age 41.3 years, range 10-80 years) with aortic insufficiency underwent reconstructive valves surgery. Eighteen patients had a commissuroplasty with or without triangular resection. In 5 patients with perforation, the valves could be reconstructed with a pericardial patch. In 12 patients with insufficiency due to aortic aneurysm, the valves were resuspended within the aortic prosthesis. In 2 patients the aortic valves were replaced intraoperatively because of unsatisfactory results. The perioperative mortality was 5.7%. The echocardiographic degree of aortic insufficiency decreased from 3.3 +/- 0.5 preoperatively to 0.45 +/- 0.53 postoperatively. Two patients were reoperated within the first week. Five of 23 patients at 1-year follow-up have mild to moderate aortic insufficiency. Mean ventricular dimensions and function at discharge and after 1-year follow-up are normal. With the new operative techniques described recently, valve-sparing corrections of aortic insufficiency are possible in an increasing number of patients, and autologous valve tissue can be saved. With more refinement of surgical technique, early postoperative results will further improve. PMID- 7785299 TI - [Experiences with the new cardioverter-defibrillator Ventak PRxII]. AB - Clinical safety and efficacy of the new third-generation implantable cardioverter defibrillator (ICD) Ventak PRxII was studied in 50 patients (pts) with ventricular tachycardia (VT) and/or fibrillation (VF). In 23 pts (46%) the ICD was implanted with a transvenous lead system as first implant and 27 pts (54%) received the Ventak PRxII as generator replacement. Intraoperatively, the mean defibrillation threshold (DFT) was 13 +/- 8 joules and 12 +/- 8 joules, respectively. One pt died perioperatively. During a follow-up of 5.3 +/- 3.8 months 3 patients died due to heart failure. During follow-up 1060 arrhythmia episodes (AE) occurred and were terminated primarily by countershock in 121 AE (11%). Antitachycardia pacing (ATP) was tried in 939 AE (89%) and was successful in 878 AE (94%). Acceleration was present in 6 AE (< 1%). We conclude that there is a high efficacy rate in AE termination by the Ventak PRxII, using ATP or countershock. Therefore, the Ventak PRxII allows a flexible approach to cardiac rhythm management. PMID- 7785300 TI - [The T-wave shock: a new reliable method for induction of ventricular fibrillation in ICD testing]. AB - During ICD-implantation it is necessary to induce ventricular fibrillation several times to determine the defibrillation threshold. In third generation ICDs there are several options to induce ventricular fibrillation. We want to present a new method, called T-wave-shock, which is first available in the PCD Jewel 7219 (Medtronic). The T-wave-shock is the delivery of a low-energy-shock into the vulnerable period after ventricular stimulation with a basic cycle-length. We applied the T-wave-shock in 46 consecutive ICD-recipients intraoperatively and at the pre-hospital-discharge test. The method is highly effective when applying the shock into the ascending part of the T-wave (98% of the patients were inducible), and the duration of cardial and cerebral ischemia during induction is short (between 3.1 and 3.8 s). This raises defibrillation efficacy. PMID- 7785301 TI - [Modern electrodes with and without steroid: effects on stimulation current of cardiac pacemakers]. AB - The aim of the investigation was to test whether new leads without steroid, a meshwire tip leads (Ionyx 4180, CPI; n = 10) and a carbon tip lead (Facet ITP 13, Vitatron; n = 10), have electrical characteristics similar to a new steroid eluting tip lead (CapSure SP 4023, Medtronic; n = 10) and their impact on the pacemaker's pacing current. Pacing thresholds, impedance, and R-wave amplitudes measured at implantation were similar for the three leads. One, 4 and 12 weeks after implantation both nonsteroid leads had significantly higher pacing thresholds at 0.1 and 0.3 ms pulse duration in comparison to the steroid lead (after 12 weeks at 0.3 ms steroid: 0.9 +/- 0.2 V, carbon: 2.1 +/- 0.5 V; meshwire: 1.5 +/- 0.5 V). This result was restricted to the carbon lead after 52 weeks. At 0.5 ms pulse duration higher pacing thresholds were obtained for the carbon lead (after 12 weeks at 0.5 ms; steroid: 0.8 V, carbon: 1.7 +/- 0.6 V; meshwire: 1.1 +/- 0.4 V). Impedance of the steroid lead was 531 +/- 61 ohms, 535 +/- 54 ohms, and 511 +/- 50 ohms, respectively, after 4, 12, and 52 weeks, whereas the carbon lead had significantly higher values with 652 +/- 84 ohms, 669 +/- 93 ohms, and 657 +/- 107 ohms, respectively. The impedance of the meshwired lead (4 weeks: 585 +/- 92 ohms; 12 weeks: 592 +/- 89 ohms; 52 weeks: 550 +/- 130 ohms) did not differ from the steroid lead.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785302 TI - [An unusual series of complications in therapy with implantable cardioverter defibrillator]. AB - A 48-year-old man with dilative cardiomyopathy and a history of resuscitation due to ventricular fibrillation received an implantable cardioverter-defibrillator (ICD) with epicardial sensing and defibrillation electrodes in March 1990. An early battery depletion due to increased electrical leakage of a filter capacitor necessitated a generator exchange in July 1990. Subsequent inappropriate discharges occurred, but no underlying cause could be documented by history, clinical examination, Holter monitoring, and beepograms. Only 3 months later was it possible to demonstrate oversensing by repeated beepograms, and a new generator and transvenous sensing electrode were implanted in October 1991. Four months later, inappropriate shocks were suspected again. Once more, history, clinical examination, Holter monitoring, and beepograms were without pathological result. At follow-up, repeated beepograms during exercise demonstrated an oversensing, and an insulation defect of the newly implanted sensing electrode close to the edge of the generator could be documented on x-ray. Since replacement of generator and sensing electrode in July 1992 the patient is doing well. He received two appropriate shocks which were associated with presyncope. ICD therapy is very complex and therefore should only be performed in centers providing the necessary personal, apparative and logistic conditions. PMID- 7785303 TI - [Autoantibodies against cardiac myosin in patients with myocarditis and dilated cardiomyopathy]. AB - Evidence accumulated in recent years indicates that autoimmunologic mechanisms may play an important role in the pathogenesis of myocarditis and dilated cardiomyopathy. In animal studies with Coxsackie B3-virus-induced murine myocarditis circulating autoantibodies against cardiac myosin have been detected. The present study investigates whether in patients with myocarditis and dilated cardiomyopathy antimyosin-autoantibodies can be detected. Patients with other cardiac diseases and healthy blood donors were used as controls. In 30 of 62 (48.4%) patients with myocarditis antimyosin-antibodies could be detected, whereas in patients with dilated cardiomyopathy only 10 of 41 (24.4%) sera contained antimyosin-antibodies (p < 0.05). In patients with other cardiac diseases, 9 of 43 (21%) sera showed antimyosin-autoantibodies (p < 0.05 vs myocarditis, not significant vs DCM). In healthy blood donors, antimyosin autoantibodies could only be detected in 1 of 39 (2.5%) sera. In Western-blot tests, the antimyosin-antibodies in patients with myocarditis bound to the myosin heavy chain. Protein A-Sepharose chromatography showed that the antimyosin autoantibodies are of the IgG-type. No organ-specificity of the antibodies for cardiac myosin could be detected, and the antimyosin-autoantibodies bind equally to myosin prepared from either cardiac or skeletal muscle, respectively. PMID- 7785304 TI - [Presentation and quantification of acute myocardial infarct using antibody-bound MR contrast medium]. AB - A magnetically labeled antimyosin (MION-AM) has previously been developed for immunospecific MR imaging in vivo. The current study was designed to extend previous feasibility studies and to correlate MR infarct size to that determined by histopathology. The left anterior coronary artery (LAD) was temporarily occluded in rabbits (n = 10) and subsequently reperfused for 1 h prior to the administration of 100 mumol Fe/kg of MION-AM (corresponding to 0.5 mg AM). One hour after i.v. administration, the infarcted myocardium appeared hypointense by MRI as a result of target-specific attachment of the magnetic T2 label to damaged but not normal myocardium. There was a close correlation between infarct size determined by MR and pathology (SE 2500/30: r = 0.92, p < or = 0.0001; SE 2500/60: r = 0.85, p < or = 0.0001). Our results are evidence that a) immunospecific magnetic probes can be utilized for cardiac MR imaging, and b) that these or similar agents may aid in the quantitation of myocardial infarct size. PMID- 7785306 TI - [Traumatic aortic rupture: diagnosis using biplanar transesophageal echocardiography]. AB - Acute aortic rupture is a typical consequence of severe blunt chest trauma often associated with rapid deceleration in car accidents. Initial diagnostic findings are often misleading and multiorgan injuries add to the diagnostic complexity; therefore, the natural history of acute rupture is usually fatal during the first 24 h after injury if left untreated. Prompt and simple diagnosis is, hence, of paramount importance for successful treatment of acute aortic rupture. Transesophageal echocardiography, particularly with a biplane or multiplane probe, currently represents the diagnostic tool of choice to meet these criteria; because of its high sensitivity and specificity transesophageal echocardiography will replace aortography as "gold standard" for diagnosis of acute aortic rupture. We report on a 47-year-old woman with severe blunt thoraco-abdominal trauma resulting from a car accident; at hospital admission abdominal injuries were predominant and diagnosis of an acute rupture of the descending thoracic aorta was made only about 18 h after admission using biplane transesophageal echocardiography. Emergency surgical revision confirmed the diagnosis of complete transsection of the descending thoracic aorta immediately after the origin of the left subclavian artery; the site of transsection was surrounded by a large hematoma. Despite successful reconstruction of the descending thoracic aorta by means of graft interposition, a recurrent local bleeding event lead to complete circulatory destabilization and, finally, to the death of the patient. PMID- 7785305 TI - [Magnetic resonance tomography findings in adult patients with congenital corrected transposition of great arteries]. AB - In four adult patients with congenitally corrected transposition (C-TGA) of the great arteries the typical anatomy and relevant additional lesions such as perimembranous ventricular septal defect (n = 3), secundum atrial septal defect (n = 2), sub-/valvular pulmonic stenosis (n = 3) and pulmonary artery dilatation (n = 4) and/or relevant tricuspid valve insufficiency (n = 3) were depicted by magnetic resonance imaging (MRI) using spin-echo and gradient-echo techniques. The severity of the additional lesions could be evaluated qualitatively. Therefore, in cases of C-TGA magnetic resonance imaging may provide additional information or in selected patients may serve as a useful alternative to conventional imaging techniques such as echocardiography and angiocardiography. PMID- 7785307 TI - [The organized brain (an essay on the structure of functional brain organization). II]. AB - This communication is dedicated to the main postulates of the author's conception about systematic-structural organization of the cerebral functions--the principles of the space and temporal dispersion of the external and internal signals, the division of connections on the mono- and oligoprojections as well as hierarchic stage of fashion and modulation of entering information, the functional multifactory of the sensory stimuli as well as principles of overlapping both afferent and efferent influences and their mutual regulation. The principle of the change of dominant participation of one brain system to another within the behavioral act's formation is one of the main postulate of our conception. These data testify to very complicate dynamic character of the function's correlation with the brain structures. This correlation depends on the self cerebral organization as well as the role in its acting the diverse afferent messages and effector reactions. PMID- 7785308 TI - [The morphofunctional bases of forebrain and cerebellum interaction]. AB - The article reviews data on structural and functional basis of forebrain and cerebellum interactions. The results of studies of cortical and thalamic structures' neuronal activity under cerebellar influence are considered. Specific and nonspecific cerebello-thalamo-cortical projection systems are analysed. Data on functioning of corticocerebellar loops as well as synaptic transmission in its various links are given. Hypotheses and modern ideas of cerebellocortical interaction' mechanisms are discussed. PMID- 7785309 TI - [The action of high-molecular linear polymers on the circulatory system]. AB - An analysis of the hemodynamic consequences of the injections of long linear polymers with high molecular weight is introduced. These injections lead to an increase of the cardiac output, to a decrease of the blood pressure, and hence cause a reduction of the resistance to blood flow. It follows that such kind of polymers is able to normalize hemodynamics under some pathophysiological conditions, e.g., during experimental atherosclerosis, ischemic state, hemorrhagic shock. An addition of drag-reducing polymers into the blood system is associated with a modification of the blood flow microstructure itself. PMID- 7785310 TI - [The neuroendocrine regulation of gonadotropin and prolactin secretion and the role of neuromediators]. AB - The paper deals with the neuroendocrine relationships between true neuromediators of adrenergic and cholinergic nature as well as the neuromediators of peptidic character and the neurosecretory neurons controlling the secretion of gonadotropines and prolactine. The properties of about 30 neuromediators of different character with consideration for the structures of the central nervous system, participation in the synthesis and secretion of gonadoliberine, gonadotropines and prolactine and hence functioning of the reproductive system as a whole are characterized. The significance of the hormonal background of sexual steroids in the system of these complex relationships is analyzed. The author's and literature findings on the time-course of changing the contents of catecholamines in the hypothalamic structures relating to the control of the gonadotropic function of pituitary body are studied; the correlation relationships between a changed level of sexual steroids and gonadotropines in the blood during the cycle and the time-course of changing the catecholamines and luliberine in the hypothalamus are discussed. The possible mechanisms of coordinating the different neuromediators of adrenergic character and amino neuromediators with various mechanisms of action in the regulation of normal activity of the reproductive system are investigated. PMID- 7785312 TI - [The physiological classification of human thermal states under high environmental temperatures]. AB - The paper deals with the physiological classification of human thermal states in a hot environment. A review of the basic systems of classifications of thermal states is given, their main drawbacks are discussed. On the basis of human functional state research in a broad range of environmental temperatures the system of evaluation and classification of human thermal states is proposed. New integral one-dimensional multi-parametric criteria for evaluation are used. For the development of these criteria methods of factor, cluster and canonical correlation analyses are applied. Stochastic nomograms capable of identification of human thermal state for different intensity of influence are given. In this case evaluation of intensity is estimated according to one-dimensional criteria taking into account environmental temperature, physical load and time of man's staying in overheating conditions. PMID- 7785311 TI - [The mechanisms of the temperature sensitivity of the hypothalamic neurons]. AB - Studies of the 1960-80-s in intact animals and brain slices showed the existence of brain temperature-sensitive neurons in the vertebrate hypothalamus. Increased firing rate of these units activates the thermoregulatory processes. Applications of synaptic blockade in slices, and of intracellular recordings and clamp technique in the last 3-4 years allowed to find that many hypothalamic thermosensitive neurons possess an intrinsic mechanism of temperature sensitivity central to. This mechanism is a change in ionic permeability of neuronal membrane. The review summarizes the results of these studies and considers possible causes of thermo-induced changes in ionic conductivity of hypothalamic thermosensitive neuron membrane. PMID- 7785313 TI - [The role of the substantia nigra in the mechanisms of the cessation of epileptic activity]. AB - In the review of literature and author's own data the participation of pars compacta and pars reticulata of the substantia nigra in mechanisms of epileptic syndrome development and cessation of epileptic activity was shown. The results are given which testified for dependence of substantia nigra-derived effects upon form and intensity of epileptic activity as well as upon neuromediator and peptidergic systems of the brain involvement. The conclusion was made concerning the significance of substantia nigra as a part of antiepileptic system of the brain in the processes of restriction and suppression of epileptiform manifestations. PMID- 7785314 TI - Complete nucleotide sequence of RNA segment 3 of bluetongue virus serotype 2 (Ona A). Phylogenetic analyses reveal the probable origin and relationship with other orbiviruses. AB - The nucleotide sequence of the RNA segment 3 of bluetongue virus (BTV) serotype 2 (Ona-A) from North America was determined to be 2772 nucleotides containing a single large open reading frame of 2703 nucleotides (901 amino acid). The predicted VP3 protein exhibited general physiochemical properties (including hydropathy profiles) which were very similar to those previously deduced for other BTV VP3 proteins. Partial genome segment 3 sequences, obtained by polymerase chain reaction (PCR) sequencing, of BTV isolates from the Caribbean were compared to those from North America, South Africa, India, Indonesia, Malaysia and Australia, as well as other orbiviruses, to determine the phylogenetic relationships amongst them. Three major BTV topotypes (Gould, A.R. (1987) Virus Res. 7, 169-183) were observed which had nucleotide sequences that differed by approximately 20%. At the molecular level, geographic separation had resulted in significant divergence in the BTV genome segment 3 sequences, consistent with the evolution of distinct viral populations. The close phylogenetic relationship between the BTV serotype 2 (Ona-A strain) from Florida and the BTV serotypes 1, 6 and 12 from Jamaica and Honduras, indicated that the presence of BTV serotype 2 in North America was probably due to an exotic incursion from the Caribbean region as previously proposed by Sellers and Maaroof ((1989) Can. J. Vet. Res. 53, 100-102) based on trajectory analysis. Conversely, nucleotide sequence analysis of Caribbean BTV serotype 17 isolates suggested they arose from incursions which originated in the USA, possibly from a BTV population distinct from those circulating in Wyoming. PMID- 7785315 TI - Expression in Escherichia coli and purification of biologically active L proteinase of foot-and-mouth disease virus. AB - The foot-and-mouth disease virus (FMDV) Lb gene was cloned into bacterial expression vectors under the control of a T7 RNA polymerase promoter. The Lb protein was expressed in both an in vitro transcription-translation system and in Escherichia coli. In vitro expression of a construct containing the Lb gene fused to a portion of the VP4 and 3D genes demonstrated cis cleavage activity that could be blocked by the thiol protease inhibitor E-64. Lb expressed in E. coli was purified from the soluble fraction by metal chelation chromatography. Purified Lb had trans cleavage activity at the L/P1 junction and cleaved the p220 component of the cap-binding protein complex. PMID- 7785316 TI - Molecular characterization of the S proteins of two enterotropic murine coronavirus strains. AB - Enterotropic strains of murine coronaviruses (MHV-Y and MHV-RI) differ extensively in their pathogenesis from the prototypic respiratory strains of murine coronaviruses. In an effort to determine which viral proteins might be determinants of enterotropism, immunoblots of MHV-Y and MHV-RI virions using anti S, -N and -M protein-specific antisera were performed. The uncleaved MHV-Y and MHV-RI S proteins migrated slightly faster than the MHV-A59 S protein. The MHV-Y S protein was inefficiently cleaved. The MHV-Y, MHV-RI and MHV-A59 N and M proteins showed only minor differences in their migration. The S genes of MHV-Y and MHV-RI were cloned, sequenced and found to encode 1361 and 1376 amino acid long proteins, respectively. The presence of several amino acids changes upstream from the predicted cleavage site of the MHV-Y S protein may contribute its inefficient cleavage. A high degree of homology was found between the MHV-RI and MHV-4 S proteins, whereas the homology between the MHV-Y S protein and the S proteins of other MHV strains was much lower. These results indicate that the enterotropism of MHV-RI and MHV-Y may be determined by different amino acid changes in the S protein and/or by changes in other viral proteins. PMID- 7785317 TI - Characterization of a protein kinase gene from two Chlorella viruses. AB - An open reading frame (ORF) with strong homology to eukaryotic serine/threonine protein kinases was found in the two Chlorella viruses SC-1A and PBCV-1. The deduced molecular weights of each putative protein kinase were 35 kDa and the predicted amino acid sequences of the two proteins were 95% identical. The ORF encoding the SC-1A protein kinase was over-expressed as a fusion protein in Escherichia coli. The recombinant fusion protein had autophosphorylation activity and could phosphorylate certain exogenous proteins. Antiserum against the recombinant fusion protein reacted with a 35 kDa protein plus three larger proteins from virus infected cells. The 35 kDa protein was a late protein; however, the 35 kDa protein was not packaged in the virion, even though virions contain protein kinase activity. PMID- 7785318 TI - Analysis of flavivirus envelope proteins reveals variable domains that reflect their antigenicity and may determine their pathogenesis. AB - Studies on the molecular basis of flavivirus neutralisation, attenuation and tropism indicate that amino acid substitutions, in different parts of the envelope gene, may be responsible for the altered phenotypes. However, the association of particular substitutions with individual characteristics has proven difficult. Comparative analysis of all known tick-borne flavivirus envelope proteins through sequence alignment and a sliding window, reveals clusters of amino acid variation distributed throughout the envelope protein coding region. Further comparison with mosquito-borne flaviviruses reveals essentially the same profile of variability throughout the envelope protein sequence although there is a major difference within the postulated B domain of these viruses which may reflect their different evolutionary development. Most phenotypically variant properties, such as serotypic differences, variants characteristic of vaccine strains, altered tropisms and neutralisation escape mutants, map within the variable clusters. Thus, we propose that natural mutagenesis and selection may occur at specific sites that do not destroy the secondary and tertiary E protein structure and that the variable clusters represent the exposed surface amino acids of the envelope protein defining antigenicity, tropicity and pathogenesis. PMID- 7785319 TI - Receptor proteins on newborn Balb/c mouse brain cells for coxsackievirus B3 are immunologically distinct from those on HeLa cells. AB - Newborn Balb/c mice are highly susceptible to infection by the six coxsackievirus serotypes of group B (CVB) and it is known that receptor for these viruses are in highest concentration in the brain as compared to other tissues. Therefore, proteins from the brain tissues of these animals were solubilized (Brain-Ext) and characterized for the identification of mouse brain receptor (MBR) proteins. Virus-blot analyses of Brain-Ext suggested that each of three virus variants of CVB3-(N, W and RD) recognized four receptor proteins designated p46, p44, p36 and p33 according to their molecular size. Similar analyses of cultured neurons from newborn Balb/c mice revealed the presence of the same four receptor proteins, while astrocytes appeared to possess only p46 and/or p44. Isoelectric focusing of Brain-Ext, focused MBR proteins in the pH range 4.0-8.5, with a peak around pH 5.7. P46 was found to be neuraminidase sensitive. A polyclonal rat antiserum (anti-MBR) protected cultured neurons and astrocytes against infection by CVB3, inhibited virus binding to these cells and recognized the same four receptor proteins on western-blots as detected on virus-blots by CVB3. However, a rabbit polyclonal anti-HeLa cell antiserum, which strongly binds to HeLa cells and protects them from CVB3 infection, neither recognized any of the receptor proteins in western-blot analyses of Brain-Ext nor inhibited CVB3 infection on cultured neurons and astrocytes. Conversely, anti-MBR did not recognize any of the receptor proteins by western-blot analysis of HeLa cell extracts nor did it inhibit CVB3 infection of HeLa cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785321 TI - A map of the Kluyveromyces lactis genome. PMID- 7785320 TI - Localization of a protein A-tagged Kex2 protein to the vacuole of Saccharomyces cerevisiae allows rapid purification of vacuolar membranes. AB - We have previously reported an immunoisolation procedure which allows purification of Kex2p-containing Golgi membranes from lysed yeast cells. In order to evaluate the use of tagging procedures in organelle isolation we set out to isolate the same Golgi membrane fraction using a version of the Kex2 protease that had been affinity-tagged at its C-terminus. This protein is found to be localized in the vacuole, providing the basis of a method for the affinity purification of vacuolar membranes. PMID- 7785322 TI - Molecular analysis of the SNF8 gene of Saccharomyces cerevisiae. AB - Mutations in the SNF8 gene impair derepression of the SUC2 gene, encoding invertase, in response to glucose limitation of Saccharomyces cerevisiae. We report here the cloning of the SNF8 gene by complementation. Sequence analysis predicts a 26,936-dalton product. Disruption of the chromosomal locus caused a five-fold decrease in invertase derepression, defective growth on raffinose, and a sporulation defect in homozygous diploids. Genetic analysis of the interactions of the snf8 null mutation with spt6/ssn20 and ssn6 suppressors distinguished SNF8 from the groups, SNF1, SNF4 and SNF2, SNF5, SNF6. Notably, the snf8 ssn6 double mutants were extremely sick. Mutations of SNF8 and SNF7 showed similar phenotypes and genetic interactions, and the double mutant combination caused no additional phenotypic impairment. These findings suggest that SNF7 and SNF8 are functionally related. PMID- 7785323 TI - Effects of phleomycin-induced DNA damage on the fission yeast Schizosaccharomyces pombe cell cycle. AB - The effect of phleomycin, a bleomycin-like antibiotic, has been investigated in the fission yeast, Schizosaccharomyces pombe. We report that in response to phleomycin-induced DNA damage, growth was inhibited and S. pombe cells arrested in the G2-phase of the cell cycle. DNA repair mutants rad9 and rad17 did not arrest and were hypersensitive to phleomycin. Cell cycle mutants that entered mitosis without monitoring the completion of DNA replication also displayed an increased sensitivity to this DNA-damaging agent. Thus, phleomycin could be used as a tool in the fission yeast S. pombe model system for the study of DNA damage and cell cycle checkpoints, or as a new selective agent. PMID- 7785324 TI - Genetic and carbon source regulation of phosphorylation of Sip1p, a Snf1p associated protein involved in carbon response in Saccharomyces cerevisiae. AB - The SIP1 gene of Saccharomyces cerevisiae is a carbon-catabolite-specific negative regulator of GAL gene transcription and acts as a multicopy suppressor of growth defects associated with impaired Snf1p protein kinase activity. The Sip1 protein is known to undergo phosphorylation when associated in vitro with the Snf1 protein kinase. We have carried out in vivo studies of the genetic and carbon control of Sip1p phosphorylation. Metabolic labeling reveals phosphorylation of Sip1p under both carbon catabolite-repressing and non repressing conditions and in both SNF1 wild-type and snf1-deletion cells. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblot assay, we detect apparent changes in Sip1p phosphorylation states in response to changes in carbon source. At least one dephosphorylation of Sip1p occurs with a shift from non-repressing carbon source to repressing carbon source. The MIG1 gene, acting through SNF1-dependent and SNF1-independent pathways, is required for some Sip1p phosphorylations. REG1 appears to be required for at least one dephosphorylation of Sip1p, whereas SSN6 appears to be required for at least one phosphorylation of Sip1p. These results reveal new complexities in carbon response signaling, and may reflect the involvement of the Sip1 protein in the same complex as the Mig1 and Ssn6 proteins. PMID- 7785326 TI - The IFH1 gene product interacts with a fork head protein in Saccharomyces cerevisiae. AB - FHL1 encodes a polypeptide closely related to the fork head protein family of transcriptional activators. Deleting this gene leads to a slow-growth phenotype with impaired rRNA maturation. IFH1 (located on chromosome IV) was isolated as a dosage-dependent suppressor partially correcting the growth defect of the fhl1 deletion. It codes for a highly hydrophilic protein with a predicted molecular weight of 122 kDa and a pI of 4.8, that is very rich in charged residues (mostly acidic) but otherwise unrelated to any known protein. Carboxy-terminal deletions removing the last third of the protein lead to a leaky growth phenotype with impaired rRNA maturation, as in the case of the fhl1 deletion. A full deletion of IFH1 is lethal, but growth was restored in a strain deleted for both IFH1 and FHL1. Thus, Ifh1p is essential for growth, but only in the presence of a functional Fhp1p protein. Conversely, its overexpression by increased gene dosage partially compensates for the genetic inactivation of Fhl1p. These data suggest a direct interaction between the Fhl1p and Ifh1p proteins, and are consistent with a model where Fhl1p is converted from a transcriptional repressor to an activator on binding of Ifh1p. PMID- 7785325 TI - UASNTR functioning in combination with other UAS elements underlies exceptional patterns of nitrogen regulation in Saccharomyces cerevisiae. AB - UASNTR, the UAS responsible for nitrogen catabolite repression-sensitive transcriptional activation of many nitrogen catabolic genes in Saccharomyces cerevisiae, has been previously thought to operate only as a pair of closely related dodecanucleotide sites each containing the sequence GATAA at its core. Here we show that a single UASNTR the unrelated cis-acting element was TTTGTTTAC situated upstream of GLN1, while in another the cis-acting element was the one previously shown to bind the PUT3 protein. When a UASNTR site functions in combination with an unrelated site, the regulatory responses observed are a hybrid consisting of characteristics derived from both the UASNTR site and the unrelated site as well. These observations resolve several significant inconsistencies that have plagued studies focused on elucidation of the mechanisms involved in the global regulation of nitrogen catabolism. PMID- 7785327 TI - Vacuolar carboxypeptidase Y of Saccharomyces cerevisiae is glycosylated, sorted and matured in the fission yeast Schizosaccharomyces pombe. AB - Vacuolar carboxypeptidase Y of Saccharomyces cerevisiae (CPYsc) has been expressed in a Schizosaccharomyces pombe strain devoid of the endogenous equivalent peptidase, employing a 2 mu derived plasmid. Immunoblot analysis revealed that CPYsc produced in the fission yeast has a higher molecular mass than mature CPYsc produced by the budding yeast. CPYsc is glycosylated when expressed in S. pombe and uses four N-linked glycosylation sites as shown by endoglycosidase H digestion. Carbohydrate removal leads to a protein moiety which is indistinguishable in size from deglycosylated CPYsc produced by S. cerevisiae. CPYsc isolated from S. pombe soluble extracts is enzymatically active and thus is presumed to undergo correct proteolytic maturation. Subcellular fractionation experiments showed a cofractionation of CPYsc with the S. pombe endoproteinases PrA and PrB, suggesting that the protein is correctly sorted to the vacuole and that these peptidases might be responsible for zymogen activation. PMID- 7785329 TI - Current awareness on yeast. PMID- 7785328 TI - Sequence, mapping and disruption of CCC2, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants and encodes a P-type ATPase belonging to the Cu(2+)-ATPase subfamily. AB - We have isolated, sequenced, mapped and disrupted a gene, CCC2, from Saccharomyces cerevisiae. This gene displays non-allelic complementation of the Ca(2+)-sensitive phenotype conferred by the csg1 mutation. Analysis of the CCC2p amino acid sequence reveals that it encodes a member of the P-type ATPase family and is most similar to a subfamily thought to consist of Cu2+ transporters, including the human genes that mutate to cause Wilson disease and Menkes disease. The ability of this gene, in two or more copies, to reverse the csg1 defect suggests that Ca(2+)-induced death of csg1 mutant cells is related to Cu2+ metabolism. Cells without CCC2 require increased Cu2+ concentrations for growth. Therefore CCC2p may function to provide Cu2+ to a cellular compartment rather than in removal of excess Cu2+. PMID- 7785330 TI - Cloning and heterologous expression of the Candida albicans gene PMI 1 encoding phosphomannose isomerase. AB - Using a DNA fragment derived from the Saccharomyces cerevisiae phosphomannose isomerase (PMI) structural gene as a probe against a random ordered array library of genomic DNA from the pathogenic fungus Candida albicans, we have cloned the C. albicans PMI 1 gene. This gene, which is unique in the C. albicans genome, can functionally complement PMI-deficient mutants of both S. cerevisiae and Escherichia coli. The DNA sequence of the PMI 1 gene predicts a protein with 64.1% identity to PMI from S. cerevisiae. Sequential gene disruption of PMI 1 produces a strain with an auxotrophic requirement for D-mannose. The heterologous expression of the PMI 1 gene at levels up to 45% of total cell protein in E. coli leads to partitioning of the enzyme between the soluble and particulate fractions. The protein produced in the soluble fraction is indistinguishable in kinetic properties from the material isolated from C. albicans cells. PMID- 7785331 TI - Tandem integration of multiple ILV5 copies and elevated transcription in polyploid yeast. AB - An industrial yeast strain was modified by introducing DNA into brewing yeast such that the derived cells contain only yeast DNA. Thus selectable markers and bacterial sequences are not present in the final strain, making this procedure attractive for the development of generally acceptable brewing yeast. Linear DNA containing the cloned ILV5 gene was introduced into lager yeast along with an unlinked circular bifunctional plasmid containing a dominant resistance marker. Resistant colonies were screened for site-directed integration of the ILV5 DNA. Candidates were examined by several methods including Southern transfer and polymerase chain reaction. In this way, a strain WM56 was identified containing three tandem copies of ILV5. The amplified ILV5 region is stable during repeated subculturing in the absence of selective pressure. Correspondingly elevated levels of ILV5 transcript in strain WM56 compared to the control (i.e. non tandem) parental strain led to increased amounts of encoded acetohydroxyacid reductoisomerase as evidenced by significantly lower diacetyl production. WM56 appears to be identical to the parental strain judged by CHEF, total restriction digestion patterns, and probing, but differs in the ILV5 region of the chromosome. The method is generally applicable to other yeast strains, and if desired, is amenable to iterated cycles of integration to increase the number of copies. PMID- 7785332 TI - Transient responses of Candida utilis to oxygen limitation: regulation of the Kluyver effect for maltose. AB - The facultatively fermentative yeast Candida utilis exhibits the Kluyver effect for maltose: this disaccharide is respired and assimilated but, in contrast to glucose, it cannot be fermented. To study the mechanism of the Kluyver effect, metabolic responses of C. utilis to a transition from aerobic, sugar-limited growth to oxygen-limited conditions were studied in chemostat cultures. Unexpectedly, the initial response of maltose-grown cultures to oxygen limitation was very similar to that of glucose-grown cultures. In both cases, alcoholic fermentation occurred after a lag phase of 1 h, during which glycerol, pyruvate and D-lactate were the main fermentation products. After ca. 10 h the behaviour of the maltose- and glucose-grown cultures diverged: ethanol disappeared from the maltose-grown cultures, whereas fermentation continued in steady-state, oxygen limited cultures grown on glucose. The disappearance of alcoholic fermentation in oxygen-limited chemostat cultures growing on maltose was not due to a repression of the synthesis of pyruvate decarboxylase and alcohol dehydrogenase. The results demonstrate that the Kluyver effect for maltose in C. utilis does not reflect an intrinsic inability of this yeast to ferment maltose, but is caused by a regulatory phenomenon that affects a key enzyme in maltose metabolism, probably the maltose carrier. The observed kinetics indicate that this regulation occurs at the level of enzyme synthesis rather than via modification of existing enzyme activity. PMID- 7785333 TI - Glucose metabolism, enzymic analysis and product formation in chemostat culture of Hanseniaspora uvarum. AB - The physiology of Hanseniaspora uvarum K5 was studied in glucose-limited chemostat cultures and upon glucose pulse. Up to a dilution rate of 0.28 h-1, glucose was completely metabolized in biomass and CO2. Above this value, increase in the dilution rate was accompanied by sequential production of metabolites (glycerol, acetate and ethanol) and decrease in cell yield. Similar results were observed upon glucose pulse. From the enzyme activities (pyruvate dehydrogenase, pyruvate decarboxylase, NAD and NADP-dependent acetaldehyde dehydrogenases, acetyl coenzyme A synthetase and alcohol dehydrogenase) and substrate affinities, the following conclusions were drawn with respect to product formation of cells: (1) pyruvate was preferentially metabolized via pyruvate dehydrogenase, when biomass and CO2 were the only products formed; (2) acetaldehyde formed by pyruvate decarboxylase was preferentially oxidized in acetate by NADP-dependent aldehyde dehydrogenase; acetate accumulation results from insufficient activity of acetyl-CoA synthetase required for the complete oxidation of acetate; (3) acetaldehyde was oxidized in ethanol by alcohol dehydrogenase, in addition to acetate production. PMID- 7785334 TI - Extraordinary sequence conservation of the PRP8 splicing factor. PMID- 7785335 TI - Plasmid reorganization during integrative transformation in Hansenula polymorpha. AB - During studies of integrative transformation in Hansenula polymorpha, it was found that transformants with plasmids possessing the LEU2 gene of H. polymorpha were frequently unstable and lost plasmids while growing on non-selective medium. These transformants possessed reorganized plasmids capable of replication in H. polymorpha. Two such plasmids were isolated and characterized. It was shown that they contain additional DNA segments which were not present in the original plasmid used for transformation. Southern hybridization analysis carried out with labeled DNA probes derived from these segments showed that they consisted of H. polymorpha DNA. The hybridization patterns indicated that corresponding sequences were homologous to several chromosomal regions. These chromosomal DNA segments apparently carried H. polymorpha autonomous replicating sequences (HARS), since plasmids bearing them could transform H. polymorpha with high efficiency and were maintained in transformants in an autonomous state. Sequence analysis of one such captured chromosomal fragment revealed several eight- to ten-base AT-rich blocks similar to the presumed HARS sequence defined by Roggenkamp et al. (1986). Analogous reorganization was also observed with respect to integrative plasmids carrying the TRP3 and HIS3 genes of H. polymorpha and the ADE2 gene of Saccharomyces cerevisiae as selectable markers. PMID- 7785336 TI - Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure. AB - An improved lithium acetate (LiAc)/single-stranded DNA (SS-DNA)/polyethylene glycol (PEG) protocol which yields > 1 x 10(6) transformants/micrograms plasmid DNA and the original protocol described by Schiestl and Gietz (1989) were used to investigate aspects of the mechanism of LiAc/SS-DNA/PEG transformation. The highest transformation efficiency was observed when 1 x 10(8) cells were transformed with 100 ng plasmid DNA in the presence of 50 micrograms SS carrier DNA. The yield of transformants increased linearly up to 5 micrograms plasmid per transformation. A 20-min heat shock at 42 degrees C was necessary for maximal yields. PEG was found to deposit both carrier DNA and plasmid DNA onto cells. SS carrier DNA bound more effectively to the cells and caused tighter binding of 32P labelled plasmid DNA than did double-stranded (DS) carrier. The LiAc/SS-DNA/PEG transformation method did not result in cell fusion. DS carrier DNA competed with DS vector DNA in the transformation reaction. SS plasmid DNA transformed cells poorly in combination with both SS and DS carrier DNA. The LiAc/SS-DNA/PEG method was shown to be more effective than other treatments known to make cells transformable. A model for the mechanism of transformation by the LiAc/SS-DNA/PEG method is discussed. PMID- 7785337 TI - Production of senescent cells of Saccharomyces cerevisiae by centrifugal elutriation. AB - The centrifugal elutriator has been used as a baby machine by loading the chamber with a population of mixed-generation daughter cells and allowing this population to grow, divide and age under continuous washing-out of newborn daughter cells. Clear peaks in the number of elutriated cells were reproducibly obtained for at least ten generations. The parent cells growing in the chamber continued to divide at the steady-state generation time of 95-100 min, showing no change in cycle time during aging. The washed-out daughter cells increased in volume during the first five generations from their steady-state value of 17 micro3 to a maximum of 34 micro3. As to be expected, the generation times of these large daughters, determined in a synchronous batch culture, were shorter (130 min) than that of the steady-state daughters (240 min), even when derived from 15 generation parents. No indication for a volume increase of daughter cells without bud was observed when a population was allowed to grow in the chamber without washing-out the smaller daughter cells. The 15-generation parent population, recovered from the chamber, had an average volume of 80 micro3 and consisted of: (i) 71% cells with more than ten scars, (ii) 13% cells with one to nine scars, and (iii) 17% daughter cells. The production of senescent cells by undisturbed growth in the elutriator chamber has been prolonged to 29 generations. The method is therefore suitable to examine what factors determine the life span of budding yeast. PMID- 7785338 TI - Sequence analysis of the right end of chromosome XV in Saccharomyces cerevisiae: an insight into the structural and functional significance of sub-telomeric repeat sequences. AB - Approximately 3.9 kb of DNA, centromere proximal to the previously sequenced Y' element at the right end of chromosome XV in Saccharomyces cerevisiae strain YP1, has been sequenced. A number of the known sub-telomeric repeat sequences were identified, including Y', core X and STRs A, B. C and D. Several of these repeat elements contain potentially functional sequences. In addition, two other members of repeated gene families were identified. The first of these shows 61% and 60% DNA sequence identity to Enolases 1 and 2 respectively. The Enolase-like sequence appears to be species specific, with three copies being found in all strains of S. cerevisiae studied. The location of the three copies is the same for all strains. The second repeated sequence has homology with known open reading frames on chromosomes III, V and XI. There are five or six copies of this sequence in all S. cerevisiae and S. paradoxus strains studied and three in S. bayanus strains. The analysis of this region and comparison to sub-telomeric regions on other chromosomes gives some indication as to the potential functional and structural significance of sub-telomeric repeat sequences. In addition, these findings are consistent with the idea that sub-telomeric regions may be targets for unusual recombination events. PMID- 7785339 TI - Nucleotide sequence and characterization of the Saccharomyces cerevisiae RPL19A gene encoding a homolog of the mammalian ribosomal protein L19. AB - A gene designated RPL19A has been identified in the region downstream from the 3' end of the Saccharomyces cerevisiae MIS1 gene encoding the mitochondrial C1 tetrahydrofolate synthase. The gene codes for the yeast ribosomal protein YL19 which exhibits 57.5% identify with the mammalian ribosomal protein L19. RPL19A is one of two functional copies of the YL19 gene located on chromosome II. The disruption of RPL19A has no effect on the growth of the yeast. The RPL19A gene contains an intron located near the 5'-end. The 5'-flanking region contains one similar and one complete UASrpg upstream activating sequence. RPL19A was also found to be adjacent to the chromosome II AAC3 gene, encoding the mitochondrial ADP/ATP carrier protein. PMID- 7785340 TI - Acid-catalysed reduction of ferrylmyoglobin: product distribution and kinetics of autoreduction and reduction by NADH. AB - The pH dependence of iron(II)/iron(III) product distribution, following reduction of the hypervalent iron in equine ferrylmyoglobin by the protein moiety of the pigment (so-called autoreduction) and by NADH (nicotinamide adenine dinucleotide, reduced) and the rate of reduction was found to depend different on pH. Autoreduction is specific acid catalysed and has a more modest temperature dependence than autoxidation of oxymyoglobin, with the activation parameters delta H# = 58.5 +/- 0.4 kJ.mol-1 and delta S# = 2.7 +/- 0.1 J.mol-1.K-1 in 0.16 mol.l-1 NaCl. The product of autoreduction is the iron(III) pigment metmyoglobin, which is slightly modified in the protein moiety. The reaction has a positive kinetic salt effect from which it is deduced that the reactive centre of ferrylmyoglobin has a charge of +1 in agreement with the structure Fe(IV) = O. Reduction by NADH involves parallel reactions of two pigment forms in acid/base equilibrium with each other with a pKa equal to 4.9, both forms yielding metmyoglobin as well as the iron(II) pigment, oxymyoglobin, as products. The protonated form reacts faster than the deprotonated form, and two-electron transfer has greater importance for the protonated form with a limiting Fe(II)/Fe(III) product ratio of 0.6 in acidic solution compared to 0.12 in alkaline solution. A square root dependence of rate on NADH concentration suggests involvement of NAD.radicals with a disproportionation as the termination reaction. PMID- 7785341 TI - Frozen storage of dressed and pre-fried portions of minced sardine muscle. AB - The aim of this work was to study the modifications occurring during frozen storage (-18 degrees C) of dressed and pre-fried portions of minced muscle of the sardine (Sardina pilchardus). Various samples were prepared in order to discover the effect on the samples of different preparatory frying times, the influence of vacuum-packing and the possible alterations in the state of preservation of the portions due to the presence of anti-oxidant agents. The results indicate that the presence of tocopherols did not have the expected effect on rancidity; it reduced the degree of rancidity reached during storage only slightly, while texture with respect to the control sample remained the same. Although the washed muscle sample presented minimum rancidity values, the tasting panel awarded it the lowest score for acceptability. In contrast, the vacuum-packed sample presented less toughness and rancidity and was considered more acceptable, in the light of which this latter procedure would appear to be the best suited for frozen storage for pre-fried battered sardine portions. PMID- 7785342 TI - Chemical and fatty acid composition of meat from Spanish wild rabbits and hares. AB - The differences in the chemical and fatty acid compositions between the meats of five Spanish wild rabbits (Oryctolagus cuniculus) and five Spanish wild hares (Lepus europaeus) for foreleg, loin, hindleg and perirenal fat have been studied. Only significant differences (P < 0.05) in the meat chemical composition were observed between rabbits and hares for dry matter and fat in loins, and for ash in hindlegs. Significant differences (P < 0.05) between saturated fatty acids in foreleg and perirenal fat and between unsaturated C-18:1 and C-18:2 fatty acids in loins were observed. PMID- 7785343 TI - Rapid determination of alpha-tocopherol in muscle and adipose tissues of pork. AB - A fast, sensitive and reproducible method for the analysis of alpha-tocopherol in pork tissues is presented. It combines saponification of the tissue and alpha tocopherol extraction in a single vessel, followed by HPLC separation and fluorescence detection. Added alpha-tocopherol was recovered quantitatively. The reduction of lipid peroxides with potassium iodide before the saponification step did not alter the amounts of alpha-tocopherol detected. Membrane-bound alpha tocopherol was not oxidized by lipid peroxides during the procedure. The coefficient of variation of alpha-tocopherol analysed using this method was +/- 4.2% for muscle and +/- 2.5% for adipose tissues. PMID- 7785344 TI - A microbiological screening method for the indication of irradiation of frozen poultry meat. AB - A microbiological screening method for the detection of irradiation of frozen poultry meat was developed on the basis of the combined use of total cell count by the direct epifluorescent filter technique (DEFT) and viable cell count by the aerobic plate count method (APC). Samples of ground, deboned poultry leg were irradiated or not with dose levels of 3, 5 and 7 kGy using an electron beam accelerator. All samples were frozen before the irradiation treatment. The average values of the differences between DEFT and APC counts in control samples and those irradiated with doses of 3, 5 and 7 kGy were 1.14 log units for control samples, and 3.16, 3.68 and 3.79 log units for the irradiated samples. A difference of at least 2 log units can therefore be considered as a limit value indicating probable irradiation treatment necessitating further investigations. PMID- 7785345 TI - [Bakery goods from irradiated and unirradiated eggs--detection of irradiation in a processed food]. AB - The detection of radiation-specific degradation products in fat has become an established method which has successfully been applied to egg products. This study is making evident the detectability of irradiated eggs as an ingredient of specified processed foods. Tart layers were produced from both irradiated and non irradiated liquid whole egg. When the fat components were isolated from the tart layers and investigated by GC/MS, the presence of irradiated eggs could clearly be shown. While the radiation-induced hydrocarbons and 2-alkylcyclobutanones could not be found in unirradiated samples, tart layers from irradiated eggs contained these substances. Especially for the hydrocarbons a satisfying correlation between radiation dose and concentration could be observed. The concentrations of radiation-induced compounds were generally lower in the tart layers than in the liquid egg samples they had been produced from. PMID- 7785346 TI - [Intake of folic acid in the total daily diet--effect of food preparation on its folic acid content]. AB - The folic acid content of total daily diet was determined by means of high performance liquid chromatography (HPLC). The contents of tetrahydrofolic acid (THF), 5-methyl-THF and 5-formyl-THF were differentiated. The mean of the folic acid content of the total daily diet samples determined analytically was 205 +/- 60 micrograms and the mean of the individual ingredients of the samples was 401 +/- 78 micrograms, which implies that about 50% of folic acid is destroyed by common household food preparation methods. If the contents of pteroylglutamic acid (PteGlu) and 10-formyl-PteGlu (which cannot be determined analytically) are added, it can be assumed that the folic acid content with only be reduced by about 40%. THF and 5-methyl-THF proved to be less stable than 5-formyl-THF. The monoglutamate portion of the total folat content was higher in the total diet samples than in the individual foodstuffs as a consequence of the action of the enzyme "deconjugase" which is released when the matrix of food-stuffs is destroyed. PMID- 7785347 TI - Utilisation of nitrates--a decisive criterion in the selection of Lactobacilli for bioconservation of vegetables. AB - This work presents results of the observations of cabbage and carrot juice fermentation after inoculation with pure cultures of lactic acid bacteria. From the point of view of nitrates, utilisation, the most suitable microorganisms found from those studied were Lactobacillus plantarum 92H, Lb. plantarum 90H and Lb. delbrueckii 37H. At the same time, other observed parameters were assessed as well for their suitability for vegetable bioconservation. PMID- 7785348 TI - Dietary fibre in white asparagus before and after processing. AB - The changes that occur, especially in the dietary fibre, during processing of white asparagus have been studied. Processing consists of submitting the vegetable to a treatment with hot water (96 degrees C), for 4 min (blanching) and subsequently immersing it in a sodium chloride solution (brining). Finally, the asparagus is sealed and sterilised at 115-116 degrees C. The study was performed on the whole asparagus and also, separately, on the apex and stem. As a result of processing there was an increase in the moisture and protein contents and a decrease in those of uronic acids and free sugars, saccharose disappearing entirely. It is concluded that the most important changes taking place in the asparagus fibre fraction during thermal treatments are the slight decrease of lignin and uronic acids, the slight increase in proteins and an important decrease in hemicelluloses. PMID- 7785349 TI - [Chemical composition of seeds and testa of Vicia faba L]. AB - Different chemical components were analysed in the seeds and in testa of Vicia faba. The seeds contain a relatively high crude protein (27.5%), a low crude fat (3.36%) content; and the lignin concentration is low (2.65%). The testa of the seeds has a very high fibre concentration and is a significant Ca-source (1.86 g/kg). The higher macroelement concentrations in the seeds were measured from K, P and Mg. The main microelements (Fe, Mn, Cu, Zn) have significant higher concentrations in the seed than in the testa. The amino acid composition of seeds is positive (compared to data of white lupine), the rate of essential amino acids is good. The concentrations of the examined antinutritive organic constituents, especially of alkaloids, are low. On the basis of chemical analysis, the production and utilisation of seeds of Vicia faba is recommended. PMID- 7785350 TI - Silicon, phosphorus, sulphur, chlorine and ash contents of Spanish commercial honeys. AB - Silicon, phosphorus, sulphur, chlorine and ash contents were determined in samples of 24 Spanish commercial honeys. Mean contents (mg/kg of honey) were 3.2 for silicon, 78 for phosphorus, 45 for sulphur and 262 for chlorine. The values for phosphorus and chlorine are high with respect to honeys from other regions. Mean ash content was 0.19%. In all cases there were high coefficients of variation, ranging from 0.43 for silicon to 0.58 for phosphorus. PMID- 7785351 TI - Fast and sensitive determination of furosine. AB - Sensitive determination of furosine in acid hydrolysates of foods was achieved by isocratic ion-pair reversed-phase HPLC and direct UV-detection within a run time of 5 minutes and levels lower than 1.5 mg per kg of protein. The formation of furosine during hydrolysis of food samples with hydrochloric acid of varying concentration was studied. Furosine formation increased linearly with acid concentration (4 to 8 mol/L). PMID- 7785352 TI - [Automated determination of total nitrogen in milk by the Dumas method]. AB - A nitrogen analyser based on the Dumas method (LECO FP-428) and equipped with a liquid injector has been tested. The intensive steam production during injection may result in poor nitrogen recoveries for volatile nitrogen compounds such as ethylene diamine. However, recoveries could be improved by slow injection and by filling the combustion tube with Cer(IV)-oxide. For the analysis of milk the instrument was calibrated with NaN3 solutions because their response was found to be less sensitive to burning conditions. Dumas-N and Kjeldahl-N of milk showed good correlation (r = 0.998). However, with the Dumas method about 6.7% (+ 0.035% N) higher nitrogen values were obtained. With a standard deviation of repeatability S(r) = 0.002% N (CVr = 0.33) and a between day reproducibility SD = 0.006% N (CVD = 1.1%) the precision of the Dumas method was similar to that reported for the Kjeldahl method. In order to avoid systematic errors the use of standard milk samples for calibration is recommended. It is concluded that modern instruments using the Dumas method allow precise measurements of nitrogen in milk with a high sample throughout. PMID- 7785353 TI - Alteration of the electrophoretic pattern of myofibrillar proteins in fish mince during frozen storage. AB - A study was made of the variations in the electrophoretic profile of myofibrillar proteins in the muscles of blue whiting (Micromesistius poutassou R.), horse mackerel (Trachurus trachurus L.) and mackerel (Scomber scombrus L.). It was shown that all species presented different deterioration patterns during frozen storage. The fish were caught at two separate times of the year (winter and summer) and were stored frozen at -18 degrees C for 1 year. The results indicate that during frozen storage, electrophoretic patterns varied according to species. Comparison of myosin heavy chain/actin (MHC/A) ratios indicates that blue whiting is the species that undergoes most alteration, and that this is more intense in fish caught in the summer than in the winter. Alteration of the MHC/A ratio was similar in horse mackerel and mackerel caught in the winter, whereas in the summer horse mackerel proved to be the most stable species. In all cases, the reduction of the MHC/A ratio was due essentially to alteration of the MHC, an effect which was particularly marked in blue whiting. Tropomyosin remained stable throughout the storage period in all three species. PMID- 7785354 TI - A comparison between conventional and fluorescence detection methods of cooking induced damage to tuna fish lipids. AB - The damage to tuna fish lipids induced by cooking was investigated in the Thunnus obesus and Th. thynnus varieties, using conventional and fluorescence detection methods, and the results were compared. As a consequence of thermal processing, the peaks at longer wavelengths increased, which correlated with other conventional indices of lipid damage (i.e. carbonyl compound formation, browning and increases in the free fatty acid content). A special significance was given to the fluorescence ratio between the maxima of the excitation emission data at 393/460 nm and 327/415 nm; increases in this ratio as a result of cooking were less dependent on the samples than were other conventional methods of measuring lipid damage. PMID- 7785355 TI - Comparison between ion chromatography and a spectrophotometric method for determination of nitrates in meat products. AB - Ion chromatography and colorimetry were used to determine nitrate ion concentration in 76 different pork meat products (salami, mortadella, wurstel, raw and cooked ham and other whole-muscle cooked products) and the results were compared. The comparison revealed that the two techniques yield quantitatively similar results, except in cases where the matrix was so complex that it might have influenced the analytical data. These results are consistent with those obtained by other authors who used UV spectrophotometric detection. PMID- 7785356 TI - Biogenic amines and microbial quality of sprouts. AB - Changes in the biogenic amine content relative to microbial activities in mung bean, lentil and radish sprouts were investigated in prepacked and "home-grown" products. Biogenic amines were determined by ion-exchange chromatography. The major groups of micro-organisms were enumerated by aerobic plate count procedures, using universal and selective media. Putrescine, cadaverine, spermidine, agmatine and spermine were detected in different concentrations, depending on the type of sprouts. In prepacked retail products the total biogenic amine content was higher than in home-grown samples (mung bean 106 micrograms/g compared to 87 micrograms/g; lentil 316 micrograms/g compared to 181 micrograms/g; radish 1486 micrograms/g compared to 252 micrograms/g). It is concluded that sprouting time and storage conditions play a major part in the hygienic quality of legume sprouts. PMID- 7785357 TI - On the origin of benzene, toluene, ethylbenzene and xylene in extra virgin olive oil. AB - Concentrations of benzene, toluene, C2-benzenes and styrene were determined in olives and the oils produced thereof, as well as at various intermediate steps during production. Concentrations were compared to those found in samples of air taken from the olive grove and the olive mills. In an exposition experiment in the laboratory, olives absorbed aromatic compounds, approaching saturation corresponding to the partition coefficient between air and oil. However, concentrations in olives delivered to the mills were 4-10 times higher than expected from the analysis of the air in the olive grove. In the olive mills, concentrations were increased further by a factor of up to 2 because of uptake from air which contained high concentrations of aromatics. Styrene concentrations strongly increased during storage of crushed olives at ambient temperature, which confirms the hypothesis that styrene is a product of metabolism. PMID- 7785358 TI - Preservation of raw milk with CO2. Sensory evaluation of heat-processed milks. AB - The effect of CO2 on the growth of psychrotrophic milk spoilage organisms was studied, both in raw fresh milk and in pure cultures of three species of Pseudomonas growing in sterilised milk. Changes of sensory properties of CO2 treated samples after heat treatment were also analysed. Inhibition of psychrotrophic growth at 7 degrees C in milk treated with CO2 to a pH 6.2 or 6.0 was impaired by a gradual reduction of the CO2 content during storage. Growth inhibition was considerably improved by pH adjustment at 24-h intervals. Sensory analysis showed significant differences between non-acidified and acidified samples after heat treatment at 75 degrees C for 20 s or 110 degrees C for 5 min. No sensory differences were found between non-acidified and acidified milks degassed before heat treatment. PMID- 7785359 TI - Extraction of ewe's milk cream with supercritical carbon dioxide. AB - The extraction of ewe's milk cream by supercritical carbon dioxide in the pressure range 9-30 MPa (90-300 bar) and at temperatures of 40 degrees C and 50 degrees C was studied. The solubility of total fat increased with pressure at both temperatures until a plateau was reached. The extraction of cholesterol also increased with pressure until a plateau was reached and it was higher at 50 degrees C than at 40 degrees C when the pressure was > or = 15 MPa (150 bar). The triglyceride composition of each extract, determined by GC, showed that extracts obtained at lower pressures were enriched in short-chain triglycerides and their concentration decreased as the pressure increased. In the other hand, long-chain triglycerides were enriched in the extracts obtained at higher pressures and their concentration rose with increasing pressure. PMID- 7785360 TI - Daily dietary copper intake in Belgium, using duplicate portion sampling. AB - Daily dietary copper intake in Belgium has been evaluated by duplicate portion sampling, heating in a microwave oven and atomic absorption spectrometric determination of this element. The mean intake value (1.5 +/- 0.4 mg/day) is similar to levels found for most other countries, but is situated at the lower end of the recommended range for a safe and adequate daily dietary intake. PMID- 7785361 TI - [Reversible changes in brain volume in anorexia nervosa]. AB - Cranial computed tomography (CT) was performed in three different samples of young women with anorexia nervosa before and after treatment. The biggest changes in cerebrospinal fluid volume were observed in the supratentorial and extracerebral-subarachnoid area, with smaller changes in the ventricles. These changes, as assessed by different methods of volumetric and planimetric measurement, were statistically significant and were correlated with the changes in body weight. Two patient groups could be distinguished on the basis of the presence or absence of cerebellar pseudoatrophy in the initial CT, and these groups also showed differences in preclinical and clinical course. PMID- 7785362 TI - [Diagnosis of psychiatric disorders in children and adolescents using structured interviews]. PMID- 7785363 TI - [Behavioral medicine]. PMID- 7785364 TI - [Responsibilities and problems in quality assurance in psychiatry and psychotherapy in childhood and adolescence]. AB - The goals of quality assurance in child and adolescent psychiatry and psychotherapy and related problems are reviewed. Three dimensions of quality assurance are differentiated: the substantive aspect (quality of the treatment process and results, quality of structural aspects of treatment facility) the area (diagnosis, therapy, staff training) and the tasks to be accomplished in the process of quality assurance (development of standards, assessment of the current situation, comparison of current situation with standards, planning and implementation of changes). Several important problems related to quality assurance are outlined and the most urgent tasks discussed in detail (development of quality standards and assessment of the current situation). It is proposed that quality assurance documentation is divided into four parts: documentation of structural characteristics of facility, basic documentation about patient, documentation of diagnostic and treatment services provided, and documentation of evaluation of services provided. An example of a therapy evaluation method (Questionnaire for Therapy Evaluation, QTE) is described. PMID- 7785365 TI - [Subjective evaluation by parents and objective findings in former perinatal risk children]. AB - Several studies have shown no correlation between individual perinatal risk factors and outcome. Rather, the children's development depends more on social factors. In our retrospective study we compared the development of 26 at-risk newborns with that of a same-sex healthy sibling 10 to 16 years later. Data were collected by interview, questionnaires and neuropsychological tests. In the parents' view, the children who were at-risk newborns had a special position in the family (close mother-child relationship, overprotectiveness, child cause for concern). They had more educational and behavioral problems and their social network was limited. With one exception (d2 test), the neuropsychological tests showed no significant differences between the two groups of children. However, overall the at-risk children had more attention deficit disorders with hyperactivity (ICD-10, F90.0) and more selected learning disturbances (F81). A division of the children into those with minor and major perinatal risk factors was not of predictive value for outcome. There was only a low correlation between the parent's assessments of the at-risk children and more objective criteria (need for professional help or special schooling). The authors discuss the types of support that should be provided to parents with at-risk newborns. PMID- 7785367 TI - [Psychological versus psychogenic--a necessary clarification of terminology]. AB - Confusion exists regarding the usage of the two adjectives psychic and psychogenic. Therefore a differentiation of the two words is necessary. We will try to do this with the help of concrete examples. Regarding the pair of terms psychic versus somatic one has to differentiate strictly between (psychic or somatic) causes on the one hand and the forms of manifestation in the psychic or somatic field of observation on the other hand. The discussion about the linguistic ruling of psychic versus psychogenic has important consequences for the responsibilities and care of the different professions: psychiatrist, psychosomatist/psychotherapist, other specialists, general physician. PMID- 7785366 TI - [The intelligence structure of autistic persons]. AB - In a research project on the genetics of autistic disorders 115 subjects were examined. An autistic disorder was diagnosed in 102 of the subjects using the standardized Autism Diagnostic Interview (ADI; Le Couteur et al., 1989/ADI-R; Lord et al., 1994). The WAIS-R or WISC-R could be administered to 42 of the subjects. The mean full-scale IQ was 84.4, slightly below the range of normal intelligence. The mean verbal IQ (89.3) was considerably higher than the performance IQ (78.9). Analysis of the subtest patterns showed the highest scores to be in those subtests measuring knowledge of dates and facts and visuospatial abilities. The lowest scores were on subtests requiring an understanding of social relations and the ability to understand concrete social actions. This subtest pattern confirms results of other studies on the intelligence of individuals with autism and was independent of gender and level of intelligence. The subtest pattern appears to be specific for autistic disorder; it has been interpreted with reference to the theory of "weak central coherence" (Frith, 1989; Shah & Frith, 1993), which postulates that in autistic individuals stimulus perception and processing occurs independently of the general context. The results suggest that the differentiation between different types of autistic disorders should be abandoned in favor of a continuum of autistic disorders with differing degrees of severity. PMID- 7785368 TI - [Disordered partner relations in neurotic diseases and treatment with psychotherapy]. AB - Couples with neurotic partner problems are characterized by considerable psychic and/or psycho-somatic complaints. Men usually judge the relationships with their spouses more satisfactory than women do. Women suffer more from conflicts in partner-relationships than men do responding to such conflicts with psychic and/or psycho-somatic complaints. Men are more disturbed by a conflict mobilizing therapy than women are. The strongest decrease of men's psychic symptoms can be found in the year after their therapy. Women's defence against psychic problems is less strong than men's. Decrease of women's symptoms can be found during therapy already. Character neuroses don't make psychic and/or psycho-somatic symptoms in a direct manner. Character neuroses rather give rise to conflicts with other people, and stress by those conflicts cause symptoms. PMID- 7785369 TI - [Markers of the "fit" between therapist and patient as determinants of treatment outcome of inpatient group psychotherapy]. AB - Within a study concerning process and outcome of inpatient longterm group treatments the specific question was tested to what extent characteristics of the "fit" between the therapist and the patients were related to treatment outcome. The study shows that a concordance in the formulation of the treatment goals seems to be favorable for a positive outcome. Similarly, congruences between the therapeutic factors of the group treatment, subjectively important for the patients, and those factors classified as typical for the treatment concept by the therapists, were related to treatment success. The results can be discussed within the context of concepts of the therapeutic alliance and might help to operationalize those concepts in a more specific manner. PMID- 7785370 TI - [Social support and social stress in tumor patients and their partners]. AB - Social support is widely believed to be an important buffer against stress in patients coping with cancer. Support efforts can, however, in turn prove to become a source of distress in themselves, both in patients and support providers. The present study was designed to explore the connections between support and emotional distress. N = 120 lung cancer patients and their relatives (n = 57) are interviewed at three intervals. Social support is assessed by multiple methods: Content analysis, a questionnaire and a confidant rating performed by experts. Cross-sectional and longitudinal analyses are combined. Content-analytical and self-report data show a correlation of support efforts and emotional distress. In the confidant rating, however, the expected differences between supportive and non-supportive spousal relationships emerge. The results are discussed from an interactional point of view. PMID- 7785371 TI - [Physicians' attitudes of relations with AIDS, cancer and metabolic patients: core conflictual relationship theme and affects]. AB - With this comes the question: Are there typical relationship patterns and affects, that appear in physicians experience of their relationships to patients with different illnesses? We asked 33 physicians about impressive experiences with one AIDS-, one cancer- and one metabolic disorder patient each. The narratives we received were evaluated with two contentanalytic methods. The relationship patterns were assessed by the Core Conflictual Relationship Theme (CCRT), developed by Luborsky. The affects were assessed by the Gottschalk-Gleser Content Analysis Scales. We found some significant differences between the relationship experience with AIDS- and cancer patients on the one hand, and metabolic disorder patients on the other hand. In relationships with critical ill AIDS- and cancer patients the physicians verbalize more death anxiety and more diffuse or nonspecific anxiety. Furthermore they show more covert hostility against the AIDS- and cancer patient, whereas they verbalize more overt hostility against the metabolic disorder patients. We found also some fine distinction between the relationship experiences with AIDS-patients on the one hand and cancer patients on the other hand. The physicians get more involved with the relationships to AIDS-patients and the closeness-distance-regulation seems to be one central issue in this relationships. PMID- 7785372 TI - [The course of immunologic parameters in inpatient psychotherapy exemplified by 2 single case studies]. AB - Psycho-neuroimmunology depicts a conceptual frame in which possible interactions between psychic and physical processes can be examined. It could be very significant in the field of psychosomatics when the courses of psychic and somatic processes are examined. However, the research results from this field of study are varied and only for a few parameters of immunity is it possible to prove correlations with psychic variables. Many of the studies that have been conducted up to date were construed as cross-section studies and possibly therefore are not very suitable for depicting the probably very complicated forms of interactions between psychic and somatic levels in an adequate manner. In the framework of stationary psychosomatic psychotherapy two single case studies were carried out in order to examine temporal connections between psychic and immunological course parameters. Both single case studies are to be viewed as explorative attempts of examining questions of examination design and organization which are highly resolved regarding time. Furthermore we report several interesting individual results which emphasize in general the correlation between psychic and somatic parameters also in the course of time. However the limits of such studies regarding the significance of the individual immunological parameters, using time serial analytical methods as well as constructing models in the field of psycho-neuroimmunology are discussed. PMID- 7785373 TI - [Physician-surgeons in Serbian medieval medicine--contribution to the history of the Serbian medical school]. PMID- 7785374 TI - [Limited or extensive surgery in gastric carcinoma?]. AB - Although the incidence of gastric cancer has dropped it is still the most frequent carcinoma of dhe digestive tract. Surgical management of gastric carcinoma was always dependent on the stage of the disease. Contemporary knowledge of gastric lymph drainage and attempts to remove metastatic glands with the tumor gave rise to more optimism. In the beginning such and approach did not fulfill expectations, but during the past decades, especially in Japan, it became evident that more aggressive and extensive surgical procedures could benefit certain groups of patients. In order to asses this new approach it is necessary to have a unique TNM classification and to perform a rigorous and systematic identification of cancer metastasis in the lymph nodal system of the stomach. Comparison of partial gastric resection with limited standard lymphadenectomy to total gastrectomy with extensive lymphadenectomy is not possible. Nevertheless, patients with gastric cancer stages Ib, II and IIIa profit from more extensive surgery. The author present the modifications in the extent of surgical procedures for the management of gastric cancer. Special emphasis is drawn to the surgical technique and results of systemic extensive lymphadenectomy. The author has demonstrated the benefits of the new extensive surgical approach in he management of gastric cancer in his series. Operative mortality in the group of patients after systemic lymphadenectomy was 6.7% and the 5-year survival rate was 21.0%. In the group of patients where gastric resection with standard lymphadenectomy was performed postoperative mortality was 14.0% and the 5-year survival was only 5.3%. PMID- 7785375 TI - [Causes of dehiscence in the anastomosis between the stomach and small intestine in our clinical data 1970-1990]. AB - Gastrojejunal anastomotic leakage occurred in our clinical material of 4284 gastric resections Billroth II type with an incidence of 0.93 percent. 62 cases with anastomotic dehiscence were analyzed, with 22 from other clinics. The most critical part of the anastomosis was the upper angle of Billroth II Hoffmeister Finsterer anastomosis. The causes were mostly local; reoperations and resuture with necrotic and devitalized tissue, impaired vascularization of the stomach and small intestine due to rough manipulation, too narrow anastomosis and too tight securing of ligatures, as well as too massive tissue aglomeration in more layers. Stomach obstruction is a significant cause, as it is dista obstruction to anastomosis, duodenal dehiscence, peritonitis or pancreatitis. Some of the local causes are likely to be solved with using of one layer of resorptive suture material or using of a stapling device. General conditions are also important, but only as factors that stress the local conditions of risk. The mortality rate in this serial is high as 70.9%, in spite of the reoperations and complex conservative treatment. PMID- 7785376 TI - [Comparative analysis of vascular injuries during times of peace and war]. AB - The authors present results of reconstructive surgical procedures in 127 non-war and 59 war vascular injures operated on in the last ten and 2 years, respectively. Non-war injures were dominated by blunt trauma, while fire arms and explosives caused most of war injuries. Two thirds of the patients were subjected to primary, and one third to secondary operations. As much as 85% of secondary operations were made in cases of war injuries. The most common reasons for inappropriate primary operations were: incomplete diagnostics, inappropriate surgical procedure and technical errors. About two thirds of the cases were isolated vascular injuries, and one third were combined injuries where in addition to blood vessels, bones and peripheral nerves were also affected. Topographically, the upper and lower extremities were most commonly affected. Most of the operations were complex reconstructive procedures such as graft interpositions or by-passes, and less frequently only suture of a blood vessel or end-to-end anastomosis were made. Fasciotomy was an auxillary method used in all patients with late vascularization syndrome, and exposure in a special "tent" in patients with wound infection. Early success was noted on 88% of operated patients. In 12% of them amputation was performed. Primary amputation (without attempts of reconstruction) was performed in 4% out of the total number of patients. After primary operations they performed (127) the authors had to undertake amputation because of failure of the primary surgery in 4% of patients, while after secondary reconstructions (primary operations performed elsewhere) amputations were necessitated in 23% out of 57 patients. A significant difference was noted which directly correlated with the number of primary and secondary operations after war (28%) and non-war (6%) injuries. PMID- 7785377 TI - [Bronchoplasty surgery]. AB - Bronchoplastic operations are analysed in 114 patients: 76 (66.67%) with bronchial carcinoma, 33 (28.94%) bronchial adenoma, 4 (3.51%) bronchial rupture or stenosis and bronchial hondroma in one case. Sleeve resection was done in 99 (86.84%) and other kind of bronchoplastic operations in 15 (13.16%). Preoperative diagnostic procedures were focused on: clinical course and symptomatology, exact location of bronchial lesion, type of tumor, mediastinal lymph nodes, bronchial three distal from the lesion and respiratory lung tests. Intraoperatively attention was toward to the evidence of peribronchial growth of tumor, mediastinal lymph nodes and lung tissue. Early postoperative course was without complications in 85 (75.89%), with complications in 26 (23.21%) but two patients died. Incomplete reexpansion or athelectasis of the entire lung or lobe but easily treated, were the commonest complications. There was no evidence of bronchial fistula or bronchial sutura at the level of submucosal growth of tumor. In certain indications bronchoplastic operations are good operative choice for surgical treatment of bronchial tumors and traumatic bronchial rupture or its sequelas-stenosis. For malignant tumors, late results, are, after this kind of operations, equivalent to those achieved after classic resections and they do not depend of the kind of surgical procedures but correlate to the nature of the tumor. For benign and slowly growing malignant tumors late results after these operations are excellent. PMID- 7785378 TI - [Surgical treatment of peroperative injuries of the duodenum]. AB - Operative duodenal lesions are rare, but often fatal complications of certain abdominal procedures. This was reported in small series with an incidence of 0.2% of all abdominal operations. The management of these injuries requests the surgeon to be familiar with a number of specific operative approaches, which are to be used according to the operative situation. In the 1985-1992, year period, 21 cases of the operative injury of duodenum were managed without mortality, and with 3 cases of transient postoperative fistula, which healed spontaneously. The most important factors in the management of this complication are the early operative recognition of duodenal injury, or early reoperation, if, in a case of duodenal fistula, distal outflow is considered insufficient. The particularities of the duodenal suture and perioperative treatment are to be well understood. Roux en Y covering of the duodenal defect by open jejunal loop is the best method in management of these injuries. PMID- 7785380 TI - [Disorders of respiratory function in rib fractures]. AB - In the one-year prospective study 71 injured patients were observed (75% male and 25% female). Traffic traumatism was the dominant case (45%). The wounded are divided in the groups with one side fracture of ribs (left/right) and on both sides fracture of ribs considering the side of fracture, and there is consideration about the kind of fracture--there are single fracture of ribs and serial fracture of ribs. The samples of artery blood were followed in PaCO2, %SaO2 and level pH in three points of time: when the patients came, after 24 and after 48 hours. In the group with the both side fracture of the ribs, the fall of worth pH was observed after 48 hours, PaCO2 is increasing to the 6.98 kPa. PaO2 is falling after 48 hours. In %SaO2 there is no considerable difference at any time, but%SaO2 is the highest in the second group. With the serial fracture of ribs wounded are considerate the fall of worth pH which is progressively increasing and is the highest after 48 hours. PaCO2 is increasing in the both groups, but with the serial fracture the worth are considerably higher. PaO2 and %SaO2 are much lower after 48 hours. The authors conclude that the wounded on both sides and wounded with serial fracture along one or several lines of with fracture of all ribs suffer the highest respiratory insufficiency (ARI), so they need artificial ventilation as respiratory support. PMID- 7785379 TI - [Experience of the surgical service and surgeons at the 1st Surgical Clinical Center in Belgrade in the primary care of abdominal war injuries 1991-1992]. AB - During the recent (1991/92) war on the territory of the former Yugoslavia, 12 of our surgeons participated in the treating of war abdominal injuries, on 8 localities with the various characteristics of combat. Treating all injuries, with adequate evidence and documentation, the general experience of all participants of our team was that abdominal injuries range from 0-12% depending on the the intensity of combat, with the mean percentage of 5.43% while combined injuries approximate 50% with the most common injuries of extremities (24%). The number of laparotomies was 65. The most common cause of abdominal injuries were bullets (75%) except in the localities with heavy combat where the explosive and bullet woundings were equally observed. The blast injuries were recorded in 3%. The most common injured organs were large (29.5%), small intestine (23.46%) liver, stomach and spleen subsequently. The severity of injury and mortality depends mostly of the number of injured organs, and multiorgan lesions were systematically observed (1.89 of injured organs SD 0.96). The total hospital mortality was 6.15% (4 cases: 2 "in tabula" and 2 later) due to multiorgan injuries with severe shock and bleeding. To achieve better results, early transportation to a place where operation could be made is necessary, with the effective first aid and good organisation of the initial management and triage. The diagnosis must be fast and effective, decision quick and the operation must deal with all the injuries primary, by the most safe surgical procedure, with the exposition of external wound. PMID- 7785381 TI - [Leiomyosarcoma of the duodenum (case report)]. AB - Leiomyosarcomas of the duodenum are rare tumors, usually presented with gastrointestinal bleeding and/or symptoms of duodenal obstruction, rarely with obstructive jaundice. If successfully removed, these tumors have better prognosis than carcinomas of duodenum or head of the pancreas. A 62 year old man in whom leiomyosarcoma of the duodenum was successfully removed by cephalic duodenopancreatectomy (Whipple's procedure) is presented. PMID- 7785382 TI - [Percutaneous transluminal angioplasty of the abdominal aorta using the "kissing balloon" technic]. AB - Percutaneous transluminal angioplasty (PTA) of the distal abdominal aorta is still rarely performed procedure. Sporadic reports come from selected institutions with extensive experience in the field of PTA. Procedure is performed using so called "kissing-balloon" technique, and may be an alternative to the surgical treatment in well selected cases. We present a 45 years old woman with intermittent claudications and infrarenal abdominal aortic stenosis, treated successfully using above mentioned technique. PMID- 7785383 TI - [Sepsis and septic shock]. PMID- 7785384 TI - [Does extracorporeal shock wave lithotripsy have a role in the treatment of biliary calculosis?]. PMID- 7785385 TI - (Vladan Dordevic, the first trained surgeon. Contribution to the history of the Serbian medical School (2). PMID- 7785386 TI - [Surgery of colorectal carcinoma--limitations and possibilities]. PMID- 7785388 TI - [Results of surgical treatment of primary hyperparathyroidism]. AB - In the period 1981-1993, 102 patients underwent surgery for primary hyperparathyroidism (HP). Parathyroid adenoma was found in 81, carcinoma in 4 and hyperplasia in 17 patients. HP was usually diagnosed late with marked skeletal or renal damage, psychiatric symptoms and hypertension. Following the first operation in our institution hypercalcemia was successfully reduced in 100 of 102 patients, in two hypercalcemia persisted after the operation and both were reoperated. Postoperative hypocalcemic syndrome (transitory hypoparathyroidism) due to advanced stage of HP and enormous calcium deficit in bones, occurred in 47% of patients (most frequently with skeletal and hypercalcemic form of the disease). PMID- 7785387 TI - [Importance of oximetry parameters in the detection of hypoxia in the early phase of septic shock]. AB - The routinely monitored variables in shock stages include: arterial pressure, heart rate, central venous pressure, pulmonary artery wedge pressure and cardiac index. With vigorous therapy it is possible to bring these values back into the normal range in both survivors and nonsurvivors. The therapeutic goal in septic shock stages is to maximize the values of cardiac index, O2 delivery (DO2) and O2 consumption (CO2). The aim of this study is to determine the relationship between O2 delivery and O2 consumption as an early sign of hypoxia. Fifteen patients with septic shock were treated in order to maximize the value of CI, DO2 and VO2. We compared the levels of these parameters between the survivors and nonsurvivors and found no significant differences after 24 hours. High levels of DO2 and VO2 do not exclude tissue hypoxia in the early stage of septic shock. PMID- 7785389 TI - [Surgical treatment of recurrent Crohn's disease]. AB - According to the literature, the incidence of Crohn's disease is 6.0:100,000, and the prevalence is 50.0-60.0:100,000. The prevalence in this countries 3.2:100,000 and the characteristics of the disease are: a more benign course, better prognosis and infrequent involvement of the colon. The incidence of recurrence is 40.0% during a 5 year period and 65% during a 10 year period. Practically, every patient operated for Crohn's disease will be reoperated once during the first five postoperative years. The experience of the authors indicates that the situation in this country is considerably better. During the period ranging from 1980-1992, a total of 70 patients were operated for Crohn's disease. In this group of operated patients 24 (34.40%) had recurrent symptoms. Seven patients (10.0%) in the series, operated at an earlier date at this Institution, were reoperated for Crohn's disease. Another 8 patients (11.43%) were also reoperated for Crohn's disease in this series, but their initial operation had been done at a different Institution (palliative or inadequate prior surgery). Indications for reoperation did not differ from indications for the initial operation: existence of surgical complications. The most important factors in the surgical management of recurrence are: assessment of disease activity and progression and adequate preoperative and postoperative nutrition in order to improve the immune response, which is often impaired by previous surgery, disease activity and inadequate management. Correct operative strategy is crucial. The authors, in both initial and reoperations, perform limited resection of the small intestine, generous resection of the large intestine and stricturoplasty and divergent stomas on the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785390 TI - [Modern surgical treatment of pulmonary tuberculosis]. AB - Correctly performed antituberculous chemotherapy, together with the early diagnostics of tuberculosis, significantly lowered the need for surgery. Surgery is limited to patients with poor or no response to chemotherapy. In the period between 1983-1992 212 tuberculous patients were operated in the Clinic for Thoracic surgery, the Institute for the Pulmonary Disease the operated patients had the following form of the disease: primary tuberculosis in 4 patients (1.87%), 104 patients (49.06%) had the postprimary form of the disease, 67 patients (31.60%) had tuberculoma (causative lesion) cavernous tuberculosis existed in 33 patients (15.57%), while only 4 patients (1.87%) had diffuse pulmonary lesion. Diagnosis of post-tuberculous syndrome was made in 68 patients (32.08%). Secondary aspergylloma existed in 36 patients while the frequency of bronchial stenosis and bronchiectasis was the same -m 31 patients (16.98% and 14.63% respectively). One patient had broncho-oesophageal fistula. Tuberculous empiema, complicating the disease, existed in 36 patients (16.98%). Comparing the two 5-years periods, (1983-87 and 1988 to 1992) the authors conclude that the number of operations for tuberculosis is decreasing. Treatment was successful in all patients except in a patient with a broncho-esophageal fistula, who died postoperatively slow lung reexpansion existed in 5 patients, and in two cases partial upper thoracoplasty had to be done in order to solve the complication of the initial treatment. In all cases postoperative antituberculous chemotherapy was performed taking in consideration the problem of possible drug-resistance. There were no recurrences. PMID- 7785392 TI - [Diagnostic and surgical approaches in the treatment of tracheal diseases]. AB - The authors present 100 patients operate for diseases of the trachea during a period ranging from 1972-1991. Stricture of the trachea was observed in 75% of pts. and tumours in the remaining 25%. Stricture resulting from tracheostomy was the most frequent. The majority of patients underwent end-to-end anastomosis. A Nevill prosthesis was implanted in 5 patients. The results were good in 93.34% of pts. The mortality was 6.6%. The most frequent operation for malignant tumours was resection of the trachea and end-to-end anastomosis. The length of the respected segment ranged from 3-6 cm. There was no mortality. The authors conclude that adequate preoperative diagnostic procedures unable good assessment of a lesions and a well planed operation with good results and no mortality. PMID- 7785393 TI - [Personal experience in the treatment of injured patients with craniocerebral injuries associated with thoracic injuries]. AB - In the Emergency Center of the Neurosurgical Intensive Care Unit Belgrade, in the one-year period (from January, 1st 1992 to December, 31st 1992), 54 injured patients with severe head injuries associated with chest trauma were treated. In all injured patients the following parameters were considered: sex, age, mechanism of injury, surgical procedures, and fatal outcome. Thirty-nine patients (72.22%) survived. PMID- 7785391 TI - [Teratogenic tumors of the mediastinum]. AB - Primary teratogen tumors of the mediastinum are rarities in clinical and pathological practice. Their polymorphic histological picture and their enormous size provoke a great diagnostic difficulty. We analyze 85 primary teratogen tumors of the mediastinum (except those that were localized in thymus) which have been diagnosed in Institute for pulmonary diseases and tuberculosis, Clinical center of Serbia, between 1973 and 1991. Material for pathohistological evaluation was obtained by surgical resection of the whole tumor in 58 patients or by percutaneous needle aspiration biopsy in 47 patients. Malignant (immature or teratomas with malignant transformation) were present in 49 (57.65%) patients and benign (mature) teratomas in 36 (42.35%). The majority of benign (mature) teratomas (83.33%) were composed of a variety of tissue elements derived from all three germ layers and 16.67% show only ectodermal and mesodermal derivates. Malignant (immature) teratomas contained both epithelial and mesenchymal incompletely differentiated elements in 67.35% of cases and in 22.45% of cases only epithelial component undergoes malignant transformation. In our series there were two cases of primary seminoma of the mediastinum and one case of primary embryonal carcinoma, primary yolk sac tumor and primary choriocarcinoma of the mediastinum. PMID- 7785394 TI - [Treatment of severe craniocerebral injuries]. AB - During 1992. 19357 patients were examined at the Department for Neurosurgery of the Emergency Centre, Clinical Center of Serbia, out of which 15879 had head injury. In addition to those necessitating hospitalisation, there was also a large number of patients with mild head injury that were not admitted for hospital management and were sent home following initial first aid. The average incidence of these patients was 45 patients per day during 1992. During 1992. a total of 1,978 patients were hospitalised, out of which 1,520 (84%) were injured. A total of 633 patients (25%) were hospitalised due to injuries sustained in traffic accidents. All patients were examined and evaluated according to the standard protocol including GCS as well. PMID- 7785395 TI - [Isolated tuberculosis of the liver--case report]. AB - Tuberculosis of the liver is rare even in areas where tuberculosis is widespread. Isolated tuberculosis of the liver is extremely rare. It usually presents as a nodular - pseudo-tumorous form. Tuberculosis of the bile ducts is even less frequent. A 37 year old woman with nodular - pseudotumorous form of tuberculosis of the liver is presented. The diagnosis was established after surgical biopsy and histology. It may be caused by the bovine type of the bacillus. The patient had an excellent response to tuberculostatic drugs. Tuberculosis of the liver must be taken into account in the differential diagnosis of the liver masses. PMID- 7785396 TI - [Mesenteric panniculitis--case report]. AB - Mesenteric panniculitis is a very rare disease usually involving the mesentery of the small bowel, less frequently the sigmoid colon or other intraabdominal fat tissue. The disease is benign with a favorable prognosis. Diagnosis is, as a rule, established at operation or autopsy and histology. A 58 year old male with this disease is presented. The paticut hod mild abdominal pain and a palpable mass. A tumor of the mesentery was suspected on CT scan. The exact diagnosis was established at operation and confirmed at histology. PMID- 7785397 TI - [A surgical technic for bilio-enterostomy]. PMID- 7785398 TI - [Biofeedback and surgery in the treatment of fecal incontinence and lesion of the external anal sphincter: long-term follow-up]. AB - INTRODUCTION: In children, damage in the anal area which affects both the external anal sphincter and the internal anal sphincter is serious problem. Biofeedback is not effective if the external anal sphincter is severely damaged, and surgery by itself cannot effect a cure for incontinence in these cases. CLINICAL CASE: a girl aged 6 yrs 8 months who from the age of two suffered from massive recurrent tricolephalosis, causing rectal prolapse, anal abscesses and fistulas, fistulectomy, and finally severe damage in the anal area with total incontinence. The treatment began with recto-anal manometry, and rectal sensitivity studies. Biofeedback was used before and after gracilis muscle transfer and colostomy. After 12 months, total continence was achieved, and has continued through 7 years of follow-up examinations. CONCLUSIONS: To treat fecal incontinence combined with severe damage in the external anal sphincter, the following procedure should be followed: manometry and sensitivity studies, reconstruction of the external anal sphincter with gracilis muscle transfer, and biofeedback. PMID- 7785399 TI - [Predictive factors in the treatment of esophageal achalasia]. AB - With aim of determining if there are predictive factors in the treatment of achalasia of the esophagus, we analyzed in a group of 119 patients variables such as age, gender, X-Rays, Chagas' disease serology and esophageal manometry before and after treatment. The only significant factor was the LES pressure post treatment but, since the sampling was heterogeneous, and the differences where the same between bad and good results, we believe it has no predictive value in the treatment of achalasia of the esophagus. PMID- 7785400 TI - [Do the physical characteristics of radiopaque markers modify the results of the measurement of colonic transit time?]. AB - This study was performed in 15 healthy control subjects (8 males- age 23-70 and 7 females age 20-74) as a way to compare the total and segmental colonic transit time with two different type of radiopaque markers. One type of markers was 3 mm cut sections of a radiopaque polietilene 14 French Levine tube, with a medium weight of 64.3 mg and a specific gravity (SG) of 1.28. The other type were 7 mm lenticular insoluble barium (lentils) with medium weight of 231 mg and a SG of 1.87. Each subject ingested 20 markers of each type with the breakfast and front and profile plain films of the abdomen were taken 24 and 48 hs after. The total colonic transit time for the polietilene markers was 17.7 hs and 27.3 hs for the barium type (BM) (p < 0.001). The segmental transit time for right colon was 2.4 hs (PM) and 9.7 hs (PM) and 9.7 hs (BM) (p < 0.001) in the left colon 9.5 hs (PM) and 11.3 hs (BM) and in rectoanun 5.9 hs (BM) with no statistical significance. CONCLUSION: the physical characteristics of the radiopaque markers can modify the results of the colonic transit times. PMID- 7785401 TI - [Viral hepatitis infection and response to the hepatitis B vaccine in hemodialyzed patients]. AB - Data from 219 hemodyalized patients receiving attention in our Hospital and other private centers in our city are shown. Mean age was 46.9 (range: 14-85), and 132 were male; mean time under dialysis was 20 months, and subjects received an average of 5 transfusions per patient year. Serological reactivity to HBs Ag, Anti HBs and IgG anti HBc by ELISA were investigated in all of them, and anti HCV by second generation enzimo-immunoassay (EIA II) in 73 HBe Ag/anti HBe system were determined in HBs Ag positive patients and those reactive to anti HCV (EIA II) were confirmed by LIA (immunoblotting of synthetic peptides LIA-TEK Organos Teknica). Recombinant anti HBV vaccine 40 mcg at 0-1 and six month were received by 81 cases without HBV markers in their sera and a protective response was considered when anti HBs titration of 10 mU/ml or more were obtained two months later. Prevalence for anti HBc and anti HBs were 38.8% respectively and that for HBs Ag was 21% with 78% of them reactive for HBs Ag. True reactivity for anti HCV (confirmed by LIA) was present in 35.6%, but it was 9.7% in our Hospital and 54.8% in private units (p < 0.0002). Anti HBs titration was done in 69/81 patients who received anti HBV vaccine, and a protective response in 49% were obtained; the other 12 patients underwent acute hepatitis B during the vaccination period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785402 TI - [Congenital hepatic fibrosis. Study of 26 cases]. AB - We studied 26 children with congenital hepatic fibrosis during the period 1971 1993. About half of the children were about the 6 years old. Only two had brothers with same disease. The chief clinical manifestation was hematemesis associated or not with liver enlargement, predominantly of left lobe. Only one case showed fever and cholangitis. Liver function tests were usually normal. Twenty-two children had portal hypertension. Liver biopsy was of definitive for diagnosis. Seven children died. PMID- 7785403 TI - [Non cardiogenic chest pain, sensorial-motor esophageal dysfunction, and provocation tests]. PMID- 7785404 TI - [Anal incontinence]. PMID- 7785405 TI - [5-ASA versus sulfasalazine]. PMID- 7785406 TI - [Lymphatics of the thoracic surface of the diaphragm especially located around the inferior surface of the pericardial sac]. AB - The lymphatics on the thoracic surface of the diaphragm, especially lying around the lateral and posterior sides of the base of the cardiac sac, were examined in 68 adult Japanese cadavers macroscopically (37 males and 24 females, aged 45-92 years, no clinical evidences of neoplasms). In this observation, a vein which drained into the terminal portion of the inferior vena cava was observed. The lymph nodes in this region were located along the vein frequently (80.9%). The vein passed through the esophageal hiatus, or penetrated the diaphragm and finally communicated with veins around the esophagogastric junction. However, lymphatic vessels were not observed passing through the phrenico-esophageal membrane and/or the diaphragm. The collecting vessels, which originated from the lymphatics, drained into the esophageal lymphatics, and it drained into the thoracic duct via the esophageal lymphatics. In pleural effusion cases, lymphatic nets were clearly observed on the thoracic surface of the diaphragm immediately under the parietal pleura. The lymphatic nets did not communicate with the diaphragmatic lymphatics around the base of the cardiac sac. Moreover, large collecting vessel from the lymphatic nets passed through the muscular crus of the diaphragm near the medial arcuate ligament and traveled inferior to merge at the original portion of the thoracic duct at the level of the renal vessels. From these observations, the lymphatics on the posterior part of the thoracic surface of the diaphragm communicated with several regional lymphatics independently. This morphological lymphatic traveling suggests that the route differs in cases of pleural effusion or cancer metastasis. PMID- 7785407 TI - An unusual coursing of the facial vein. AB - During the dissections of 50 adult cadavers for educational purposes, we found a 45-year-old male cadaver with an abnormally coursing facial vein which has joined the retromandibular vein at a higher level--in the parotid gland--on the right side of the face. This anomaly has also been detected radiologically. PMID- 7785408 TI - [A case of mandibular retromolar canal: elements of nerves and arteries in this canal]. AB - The large bilateral mandibular retromolar canals were found in a 47-year-old Japanese man. This paper presents the nature and distribution of the elements of nerves and arteries in the left retromolar canal which were able to examined. The left mandibular retromolar canal arose from the bifurcation of the mandibular canal at 18 mm anterior to the mandibular foramen and it opened on the surface of the retromolar fossa at 13 mm posterior to the third mandibular molar. The total length of the retromolar canal from the bifurcation to the retromolar foramen was about 16 mm, and 2.5-2.6 mm in diameter. The radiographic image of this retromolar canal was a liner shadow with thin radiopaque anterior and posterior borders cast on a lateral radiography of the left half of the head. Within the retromolar canal, the artery that was branched from the inferior alveolar artery ran through the canal forwards and joined with the branches of the buccal artery and the facial artery, and then gave off the superior and inferior labial arteries. The nerve (R. retromolaris) in the retromolar canal derived from the inferior alveolar nerve trunk and branched off to the following areas: the third mandibular molar, the mucosa of retromolar triangle, the buccal mucosa, and the buccal gingiva of the mandibular premolar and molar region. The retromolar canals and foramina were found in 8 out of 41 Japanese skulls. Clinically, if the arteries in the retromolar canal become injured, complications may arise such as bleeding, and iatrogenic nerve damage may lead to paralysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785409 TI - Anomaly of the ulnar artery arising from the brachial artery. AB - A high origin of the ulnar artery was encountered in the body of an 87-year-old Japanese man in the course of normal anatomic dissection at Nara Medical University. The left ulnar artery originated from the brachial artery at the height of the left inferior angle of the left scapula and passed medially to the brachial artery and the median nerve. In the forearm, the ulnar artery passed deep to the flexor carpi ulnaris muscle. Thereafter, the two branches from the ulnar artery contributed to form the superficial and deep palmar arterial arches. The left brachial artery was divided into two terminal branches of the radial and common interosseous arteries. PMID- 7785410 TI - CT measurement of the normal brain ventricular system in 100 adults. AB - Examination of 100 voluntary cases with no physical or neurological deficit revealed that the sizes of the cerebral ventricles increase with age in both sexes. According to regression analysis in women, increase in the size of the third ventricle by age was statistically significant. Compared to women, the size of the third ventricle was larger in men. In the measurements of the lateral ventricles, it was observed that bifrontal the cerebroventricular index in men and the bicaudal cerebroventricular index in women increase significantly with age. The indices showed no significant difference between the two sexes. PMID- 7785411 TI - Axonal elongation of grafted, embryonic inferior olivary neurons in the adult rat cerebellum and their synaptic formation on host Purkinje cells. AB - Although the brain grafting of adult mammals had failed to show reinnervation of host targets, embryonic neural tissue grafted to adult brains has been reported to establish new neuronal connections. However, the trajectories of growing axons of grafted neurons in the host brain are poorly understood. To study the morphological aspects of the trajectories of growing axons of grafted neurons in detail, ventromedial medulla containing the inferior olivary nucleus of 14-day rat embryos were grafted into the hemicerebella of 8-week-old adult rats whose inferior olivary neurons and climbing fibers were previously destroyed. The cerebellum and the inferior olivary complex of host rats were histologically examined 1-6 weeks after surgery. The heterotopically grafted neurons sent their axons into the white matter and the molecular layer of the host cerebellum. These growing fibers made plexus formation in the molecular layer, ending with axo somatic and/or axo-dendritic synapses on host Purkinje cells whose afferent climbing fibers had been eliminated. These results show that the growth cones of growing axons arising from the grafted neuron can find and reach host targets along unusual pathways, and that some of the mature host Purkinje cells retain the ability to form synapses with newly developing axons from the grafted immature inferior olivary neuron. PMID- 7785412 TI - Immunohistochemical studies on supporting cells in the adrenal medulla and pineal gland of adult rat, especially on S-100 protein, glial fibrillary acidic protein and vimentin. AB - In the adrenal medulla and pineal gland, the morphological and chemical nature of supporting cells were examined immunohistochemically. In the adrenal medulla, supporting cells in noradrenaline (NA)-cell regions showed similar and intense immunoreactivities to the three glial marker proteins, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin, forming a network, while those in adrenaline (A)-cell regions were less numerous and their immunoreactivity was positive to S-100 protein but negative to GFAP and, at least in part, negative to vimentin. In the pineal gland, supporting cells in the stalk and the proximal region of the body portion formed a network and showed immunoreactivities to the three antibodies, while those in the distal region of the body portion were less numerous and their immunoreactivity was positive to S-100 protein and vimentin, but negative to GFAP. Thus, the distribution pattern and chemical nature of supporting cells showed regional differences in both glands. There were several similarities in supporting cells between those in NA-cell regions of the adrenal medulla and in the stalk and the proximal region of the body portion of the pineal gland, and also between in A-cell regions of the adrenal medulla and in the distal region of the body portion of the pineal gland, respectively. The biological and functional significances of these results are discussed. PMID- 7785413 TI - Architecture and function of the extravascular fluid pathway: special reference to the macula cribriformis in the diaphragm. AB - Silver staining, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) have been used to delineate the structure and function of the extravascular fluid pathway of the diaphragm of monkeys, rats, mice and rabbits. The submesothelial connective tissue was examined by SEM using the NaOH maceration method. A sieve-like structure, the macula cribriformis, was found in the submesothelial connective tissue on the peritoneal side of both the muscular and tendinous portions. The macula cribriformis, which consisted of densely packed collagen fibrils, was oval, spindle and polygonal in shape and ranged in diameter from 20 to 300 microns with 5-300 foramina (3-15 microns). The macula cribriformis was located between peritoneal mesothelial cells with stomata and subperitoneal lymphatic capillaries. Intraperitoneally-injected latex particles were carried into the diaphragmatic lymphatic capillaries via the peritoneal stomata and the foramina of the macula cribriformis. These results support the hypothesis proposed by Kihara (Okajimas Fol Anat Jpn 28: 601-621, 1956) that the macula cribriformis is a pre-lymphocapillary pathway, one of the extravascular fluid pathways. PMID- 7785414 TI - Distribution and size of cerebellar and thalamic projection neurons in the trigeminal principal sensory nucleus and adjacent nuclei in the rat. AB - Using retrograde axonal transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), the distribution and size of the cerebellar and thalamic projection neurons were demonstrated in the trigeminal principal sensory nucleus (Vpr) and four adjacent nuclei: the trigemino-angular nucleus (Ta), the supratrigeminal nucleus (SupV), the intertrigeminal nucleus (IntV) and the juxtatrigeminal nucleus (JxtV). In the control animal, the size of the constituent neurons of these five nuclei was also analyzed. The mean size of the somata was significantly (p < 0.05) different among these nuclei: it was largest in the Ta, followed by the IntV, SupV and JxtV, and smallest in the Vpr. After cerebellar and thalamic injections of WGA-HRP, labeled neurons were found in all of these nuclei. The cerebellar projection from the SupV and the thalamic projections from the Ta, SupV and IntV were observed for the first time in this study. The proportion of neurons projecting to the cerebellum and the thalamus varied in these nuclei. In the Ta and IntV, the majority of neurons were labeled after cerebellar injections, whereas nearly all neurons in the Vpr were labeled after thalamic injections. In the SupV and JxtV, thalamic projection neurons were greater in number. Thus, each nucleus examined in this study had distinct organizations concerning the soma size and the mode of projection to the cerebellum and the thalamus. PMID- 7785415 TI - Lateral plate mesoderm and guidance cues for cutaneous nerve growth in the avian body wall. AB - Transplantation of the somatic layer of the lateral plate mesoderm (somatic mesoderm) was performed using the quail-chick chimera system in order to evaluate whether the connective tissue acts as guidance cues for the developing cutaneous nerve in the body wall. When quail somatic mesoderm at the sacro-coccygeal (pudendal) level was transplanted into the chick somatic mesodermal region at the thoracic level, the ventral nerve exhibited the pudendal type of branching pattern in the thoracic region. However, the cutaneous nerve course remained the thoracic type. These results suggest that the connective tissue derived from the somatic mesoderm provides cues for the determination of the nerve branching pattern. In contrast, the pathway selection might require other guidance cues than the somatic mesoderm in the ventral cutaneous nerve growth in the body wall. PMID- 7785416 TI - Agenesis of the celiac trunk: an angiographic case. AB - In the angiography performed for a clinical diagnosis, a unique case of "agenesis of the celiac trunk" was encountered in a 42-year-old Turkish male. There was instead an artery which arose from the aorta at the level of the first lumbar vertebra, and supplied blood to the territory of both the celiac and superior mesenteric arteries by giving rise to the splenic, the jejunal, the ileal, the pancreaticoduodenal, the proper hepatic and the left gastric arteries, consecutively. PMID- 7785417 TI - Fine incremental lines observed on the enamel surfaces with a prismless structure in human teeth after phosphoric acid etching. AB - In human tooth enamel, the surface prismless layer contains liner laminas homologous to the cross-striations of enamel prisms other than the Retzius lines, while these lines terminate on the perikymata or run in parallel with the enamel surface. In our present scanning electron microscope observations after phosphoric acid etching, many fine incremental lines (FIL) running transversely were found on the inner occlusal enamel with a prismless structure in a young permanent premolar. Almost the same structures were also found on the upper coronal enamel with scattered prismless and indistinct prism structures in an exfoliated deciduous molar, and the FIL occasionally went across the indistinct prisms or caused the lower half of the prisms to disappear. Their intervals ranged from about 0.5 to 2 microns; less than the diameter of the prisms. Such results suggest that the FIL are not the termination of the laminate striations in the surface prismless layer, but that the previously unnoticed patterns sometimes formed by the sequential completion of the activity of ameloblasts which interact with each other in a transverse row at the final stage of matrix formation. PMID- 7785418 TI - Morphological studies on the kidney of the spontaneous nephrotic (ICGN) mice in the late stage. AB - Spontaneous nephrotic (ICGN) mice develop proteinuria, hypoproteinemia and hypercholesterolemia. These symptoms steadily progress to chronic renal failure. Details of the changes of the kidney, in the late stage (more than 5 months old) were investigated by both light and electron microscopy. The kidney exhibited a slightly whitish, granular surface and the cortex became thinner and contained fibrous lesions, in which clusters of unaffected and occluded renal tubules were randomly scattered. In the juxtamedullary and outer medullary zone, there were highly dilated renal tubules, which sometimes contained urinary casts. The glomerulus exhibited basement membrane thickening in the capillary loops and the capillary lumen was narrowed in size and sometimes occluded. No detachment of the podocyte from the basement membrane was observed and the podocyte foot-processes were extensively fused, causing their characteristic slits to be lost. The thickened basement membranes were found both in the glomerulus and around the occluded renal tubules, while the basement membrane in the dilated renal tubule appeared normal. Therefore, the basement membranes of the glomerulus and renal tubules appear to react differently in the pathogenesis of the condition. In conclusion, ICGN mice are a good model for not only the nephrotic syndrome but also for chronic renal failure. PMID- 7785419 TI - Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities. AB - Six adults and 2 children with focal inhibitory motor seizures (ictal paralysis) were evaluated during a 4-year period. Paresthesias at seizure onset occurred during some seizures in all patients, and focal clonic activity followed paralysis in 4. EEG-CCTV recordings of the seizures in 2 patients showed that ictal paralysis coincided with an ictal discharge starting in one centroparietal area. MRI showed centroparietal structural lesions in six patients. One patient with a normal MRI scan had right centroparietal hypometabolism on PET. Inhibitory motor seizures must be differentiated from transient ischemic attacks and migraine. In our patients a centroparietal epileptogenic focus was suggested by neuroimaging studies, and in 2 instances by ictal EEG. PMID- 7785421 TI - Rasch analysis in the development of a rating scale for assessment of mobility after stroke. AB - The study describes the development of a rating scale for assessment of mobility after stroke. It was based on 74 first-stroke patients, 40 men and 34 women, each assessed three times during rehabilitation. Their median age was 69 years, and they represented all degrees of severity of paresis. Content, construct, criterion and convergent validity were examined, as well as the inter-rater reliability. The final rating scale has three special characteristics: 1) it reflects the regularity in the recovery of mobility after stroke; 2) the sum of item scores comprises the information contained in the 10-item subscores; 3) the score sum is independent of age, side of hemiparesis, and gender of the patient. Latent trait analysis (Rasch) was found to be an ideal model for statistical investigation of these properties. PMID- 7785420 TI - Guillain-Barre syndrome in south-west Stockholm, 1973-1991, 1. Quality of registered hospital diagnoses and incidence. AB - We describe the incidence and explore the quality of registered diagnosis for Guillain-Barre syndrome (GBS) in a population-based retrospective study in South West Stockholm (SWS), Sweden, during the period 1973-1991. We used data on registered hospital discharges and open-care visits, and from medical records. Medical records were available for 83 (80.6%) of 103 patients with registered GBS diagnosis at discharge from hospitals. For 69 (83.1%) of such patients, the information from the hospital record fulfilled the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) clinical criteria for GBS. One out-patient presented with suspected GBS. In contrast, none of 40 patients discharged with diagnosis of unspecific polyneuropathy fulfilled the above mentioned criteria. During the period 1973-1991, the mean annual incidence of GBS per 100,000 was 1.74, 95% CI 1.41-2.12, from register data and 1.49, 95% CI 1.19-1.85, after excluding those not fulfilling criteria for GBS. The age adjusted incidence after validation was higher for men, 1.64, 95% CI 1.19-2.21, than for women, 1.46, 95% CI 1.05-1.99. An increasing incidence with age was found, presenting the age-specific curve a bimodal shape. The results of this study confirm that hospital discharge diagnostic data in Sweden can be used for purposes of epidemiological research and surveillance for GBS, and show that the incidence of GBS in SWS compares to those described in other populations. PMID- 7785422 TI - Recurrent hypertensive intracerebral hemorrhage. AB - Hypertensive intracerebral hemorrhage has been considered as a one-time event with rare recurrence. This observation is quite different from our experience in Taiwan. We, therefore, conducted a systematic review of our series of consecutive patients with recurrent bleeding. During a 2-year period, we encountered 47 patients with recurrent hypertensive intracerebral hemorrhage from a total of 892 consecutive patients with hypertensive hemorrhage (5.3%). There were 25 men and 22 women with a mean age of 59 +/- 10 (range: 36-78) years at the onset of the first hemorrhage and 62 +/- 9 (range: 39-80) years at the second hemorrhage. The median interval between 2 hemorrhages was 2 years and 4 months (range: 1 month to 8.5 years). All except one recurrent hemorrhages occurred at a site different from the previous one. Of the 38 patients admitted to our hospital for both hemorrhages only 5 were regularly treated with antihypertensive therapy. The outcome for the recurrent bleeding was grave: 26% died and 51% became totally dependent or vegetative. Recurrent hypertensive hemorrhage is not as rare as previously thought; it comprises 5.3% of our patients with hypertensive intracerebral hemorrhage. The recurrent hemorrhage, however, rarely occurs at the same location as the previous one. Uncontrolled hypertension appears to be an important risk factor for the recurrence. Control of blood pressure after the first bleeding should be attempted to prevent recurrent hemorrhage. PMID- 7785423 TI - A syndrome of olivopontocerebellar atrophy and deafness with onset in infancy. AB - Olivopontocerebellar atrophy (OPCA) is rare in childhood and onset in infancy is uncommon. We encountered 11 consecutive children with clinical and radiological features of OPCA which started in infancy. In addition to cerebellar ataxia, these children also had sensorineural deafness and speech impairment. Of the present cases, 8 were sporadic and the pedigree patterns in 3 (with a sibling also involved) point to an AR inheritance. The CT scan showed varying degrees of cerebellar and pontine atrophy. The underlying genetic and neurochemical substrates of this syndrome await further study. PMID- 7785425 TI - F wave in acute cerebellar damage. AB - Studies of occurrence of the F wave can be considered as a method of assessment of excitability of the spinal cord motoneurones. So far it has been analyzed in relation to the damage to the pyramidal and extrapyramidal systems. In the present paper, various parameters of the F response (maximal and mean amplitude absolute and in relation to the M response, frequency of occurrence of all and identical F waves, minimal latency and chronodyspersion) were given analysis in 15 patients with hypotonia after acute cerebellar damage, and in 35 healthy subjects. In the patients, the F response was found to be decreased in amplitude (mean-absolute and ratio to M) and in frequency. Therefore, a conclusion can be drawn that it confirms the decrease of segmental motoneurone excitability after cerebellar damage. PMID- 7785424 TI - Immunocytochemical detection of tumor necrosis factor-alpha in infiltrating tumor cells in the cerebrospinal fluid from five patients with leptomeningeal carcinomatosis. AB - We studied the immunoreactivity for tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) cell smears from five patients with leptomeningeal carcinomatosis (LC). Immunostained TNF-alpha-positive tumor cells had brownish deposits in the cytoplasm, but no deposits were observed in the nucleus. The intensity of the TNF-alpha staining was greater in these tumor cells than in macrophages from patients with inflammatory diseases. Approximately 27-72% of the tumor cells were found to be TNF-alpha immunoreactive in all five samples from the patient with LC. These results suggest that the large amount of TNF-alpha produced by infiltrating tumor cells may play an important role in the development of the tumor. PMID- 7785426 TI - Microsatellite D21S210 (GT-12) allele frequencies in sporadic Alzheimer's disease. AB - Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid precursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. PMID- 7785427 TI - Absence of 4,977-bp deletion of blood cell mitochondrial DNA in patients with young-onset Parkinson's disease. AB - Decreased mitochondrial Complex I activities and a 4,977-bp deletion in mitochondrial DNA (mtDNA) have been reported in patients with Parkinson's disease. Based on the assumption of possible links between this 4,977-bp deletion and the etiology of Parkinson's disease, we analyzed mtDNA of blood cells from 15 patients with young-onset Parkinson's disease after the DNA was amplified by polymerase chain reaction. We could not detect the 4,977-bp mtDNA deletion in any of these patients. This result suggests that Parkinson's disease is not a mitochondrial disease due to the 4,977-bp mtDNA deletion. The 4,977-bp deletion in mtDNA appears to be an age-related phenomenon. PMID- 7785428 TI - Regional cerebral glucose metabolism in autopsy-confirmed Creutzfeldt-Jakob disease. AB - Regional cerebral glucose metabolism was measured in a 72-year-old man, with Creutzfeldt-Jakob disease (CJD), by positron emission tomography using [18F]-2 fluoro-2-deoxy-D-glucose as the tracer. The diagnosis of CJD, a rare neurodegenerative disorder, was confirmed at autopsy 13 months later. Compared with five unaffected elderly men, the patient had reduced metabolism heterogeneously distributed throughout the brain. The hypometabolism was most evident in the right hemisphere, particularly in the posterior frontal, parietal, Sylvian, and temporal regions. This left-right asymmetry is more extensive than that previously reported in Alzheimer's disease, and may provide a useful metabolic marker for early diagnosis of CJD. PMID- 7785429 TI - High levodopa use in periodically time-clustered, Icelandic birth cohorts. A vestige of parkinsonism etiology? Europarkinson Preparatory Activity Research Group. AB - We evaluated levodopa use (LDU) by the Icelandic population focusing on: 1) annual gross levodopa (LD) sales from wholesalers to pharmacies for the period 1978-1990, using a reported method; 2) data from a prescription survey conducted from October 1st, 1990 to March 31st, 1991; and 3)raw and reported data on prevalences of Parkinson's disease (PD) in 1963 in this country. The standard for adjustments and reference population for LDU comparisons was the Swedish in 1984. Crude gross sales of LD in Iceland in 1990 and in Sweden in 1984 amounted to 1.67 and 1.35 DDD/1000 person days respectively. After respective adjustments for age, and for age and the infant mortality rates, taken as an indicator of health care quality, LDU in Iceland in 1990 was found to be 1.82 and 1.63 (95% CI 1.47-1.89) times that for Sweden. Prevalences of LD-prescription recipients in 1990-1991 and of PD in 1963 increased with age; however, those of drug users were higher than those of PD among the elderly. Higher-than-expected prevalences of PD and LD prescription users (there being a partial overlap between these two categories) were found in periodically-clustered, one-year birth cohorts. These results support the notion that Iceland has a high LDU and suggest that this variation is due to a high prevalence of LD responsive disorders. Cohorts born after registered whooping cough outbreaks in Iceland may account for the magnitude and birth-related pattern of PD prevalences and LDU levels. PMID- 7785430 TI - Levodopa use in Denmark: high levels in Greenland and the Faroe Islands. Europarkinson Preparatory Activity Research Group. AB - Levodopa (LD) sales from wholesalers to pharmacies during the periods, 1977-1989 in Denmark, 1981-1989 in Greenland, and April 1988-May 1989 in Danish counties and the Faroe Islands, were evaluated using a reported method and a procedure expressly developed for assessment of random variation comparative levodopa use (LDU) measurements. The reference population for comparison of LDU was the Swedish from 1984. LDU diffusion had stabilized by 1989 in Denmark, but considerable annual increments of LD sales were still seen in Greenland in 1989. Crude LDU in Denmark and most Danish counties amounted to a level similar to that of Sweden. Adjustments for age and infant mortality rates, taken as an indicator of socioeconomic development, disclosed statistically significant twofold levels of LDU in the Faroe Islands and Greenland, and lowest LDU in urban regions. The social or biological factors underlying such differences in drug use remain unknown. PMID- 7785431 TI - Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson's disease--a retrospective comparison. AB - INTRODUCTION: Autonomic dysfunction (AD) can be a feature of both multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD), conditions that are frequently misdiagnosed in life. Most studies on AD in MSA and IPD are based on clinical cases without pathological verification. MATERIAL AND METHODS: We retrospectively analysed AD in 135 pathologically confirmed cases of IPD and in 33 of MSA from the UK PD Society Brain Bank. RESULTS: MSA started at a younger age than IPD (54.4 +/- 10.7 yrs versus 60.6 +/- 10.8 yrs), and AD began earlier in the course of the illness All MSA patients had some degree of AD in life whereas AD was absent in 24% of IPD patients. Although each of five autonomic domains was affected in variable numbers of IPD patients, AD in MSA generally involved more autonomic domains than in IPD, and to a more severe degree, in particular with regard to inspiratory stridor. CONCLUSIONS: These results indicate that the presence of autonomic disturbance alone does not distinguish between MSA and IPD in individual cases. However, the presence of severe AD, of AD preceding parkinsonism, or of inspiratory stridor, are all individually suggestive of MSA. PMID- 7785432 TI - [Antiulcer effect of polycyclicamine compound HH01 on experimental gastric ulcer in rats]. AB - HH01(1-methyl-3,4,5,6,9,10-hexahydro-7H-cyclopenta [j,k]-1,3-dioxolo [4,5-h] pyrrolo[2,1-b] [3]-benzazepine) A and B in doses 30 mg.kg-1 and 60 mg.kg-1 were shown to protect gastric mucosa of rats from damage induced by absolute ethanol, cold-immersion stress and pylorus ligation. No effect was found in indomethacin model in mice. HH01 was found to decrease secretion of gastric juice and HCl in pylorus ligated rats. The content of DNA in gastric juice of animals treated with HH01 was lower than in control. The results suggest that HH01 is effective as an anti-ulcer agent, but its mechanism of action is yet unknown. PMID- 7785433 TI - [Synthesis of Achyranthes bidentata polysaccharide sulfate and its antivirus activity]. AB - Sulfation of Achyranthes bidentata polysaccharide (Abps) with sulfuric acid or sulfur trioxide-pyridine or chlorosulfonic acid-pyridine was studied. A homogeneous sulfation method with good yield of 82.11% was obtained, using chlorosulfonic acid in an excess of pyridine. Sulfated Achyranthes bidentata polysaccharide was obtained as an amorphous sodium salt easily soluble in water. The UV and IR spectrum of Abps sulfate showed absorptions at 208, 268, 286 nm and 1232, 823.6 cm-1 respectively. The sulfur content of the products was found to be 20-22%. The degree of substitution varied from 2.8 to 3.2. It showed that the hydroxy group of Abps was almost completely esterified by chlorosulfonic acid. The Abps sulfate was shown to have high activity as anti-HBsAg and HBeAg. It is also effective on simple herpes virus type-I. PMID- 7785434 TI - [Comparison of multiple dosage bioavailability between phenylpropanolamine controlled release suspension and conventional tablet in healthy volunteers]. AB - Compared studies between the pharmacokinetics of phenylpropanolamine (PPA) controlled release suspension (CRS) and that of PPA conventional tablet in 10 healthy volunteers showed that the maximal plasma concentration (Cmax), the minimal plasma concentration (Cmin) and the fluctuation index (FI) values were 169.06 +/- 7.76 ng.ml-1, 82.80 +/- 4.29 ng/ml-1 and 0.20 +/- 0.04 respectively for PPA CRS, 180.5 +/- 8.91 ng.ml-1, 76.18 +/- 5.97 ng.ml-1 and 0.81 +/- 0.07 respectively for the conventional tablet. The Cmax and FI of PPA CRS were significantly lower compared with those of the conventional tablet (P < 0.01) during steady state. The Cmin of PPA CRS was higher than that of the conventional tablet (P < 0.05). PMID- 7785435 TI - [Inhibition of chemically induced microvascular leakage by ONO-1078, a leukotriene antagonist, in rat skin]. AB - This study is to determine whether ONO-1078, a potent leukotriene antagonist, influences chemically induced rat skin microvascular leakage which is considered to be, at least in part, due to stimulation of sensory nerve ending and release of sensory neuropeptides. Evans blue dye was used as a tracer for plasma leakage. Intradermal injections of chemical stimuli, histamine (10 micrograms), capsaicin (10 micrograms) and formalin (0.5 mg), evoked Evans blue dye extravasation in rat skin. Intraperitoneal ONO-1078 dose-dependently inhibited the dye extravasation induced by these stimuli, with ID5v values of 1.98 mg.kg-1 for histamine, 1.78 mg.kg-1 for capsaicin, and 2.23 mg.kg-1 for formalin. In contrast to chlorpheniramine, a H1 receptor antagonist, the inhibitory effect of ONO-1078 was weaker on histamine, but more potent on capsaicin and formalin. The inhibitory effect of dexamethasone was more potent than that of ONO-1078 on these stimuli. On the other hand, ONO-1078 inhibited the dye extravasation induced by leukotriene D4 (0.05 micrograms), but showed no effect on those induced by substance P (0.5 micrograms, a sensory neuropeptide), a larger dose of histamine (100 micrograms), and bradykinin (1 microgram). These results suggest that inhibition of chemically induced skin microvascular leakage by ONO-1078 may be mediated by inhibiting the release of sensory neuropeptides from capsaicin sensitive sensory fibers. PMID- 7785437 TI - [Tyr-D-Ala-Gly-Phe-D-Leu (DADL) solid-phase synthesis and its effects on immune function]. AB - DADL, a delta-receptor selective enkephalin analogue, was prepared with the technique of solid-phase peptide synthesis. It was found to stimulate directly the proliferation of mouse splenic lymphocytes dose-dependently. However, synergistic effect of DADL at different concentrations with ConA and LPS were not found. In addition, TNF-alpha production was increased by ip DADL (1.0 mg.kg-1 x 6 d) in mice and the production of LPS-induced TNF-alpha in mouse peritoneal macrophages was enhanced after DADL was added in vitro. These results suggest that DADL, like enkephalins, exerts some immunoregulatory activities. PMID- 7785436 TI - [Effects of tetrandrine on cardiac hemodynamics of hypertrophied left ventricle from deoxycorticosterone-salt hypertensive rats]. AB - Effects of tetrandrine (Tet) on cardiac mass and hemodynamic parameters were studied in deoxycorticosterone-salt (DOCA-salt) hypertensive rats. Treatment with Tet (50 mg.kg-1, qd x 9 wk) markedly lowered systolic blood pressure and left ventricular (LV) weight. Study on isolated working heart demonstrated that the Tet group compared with the LVH group, AP, LVSP, +/- dp/dtmax, LVDP, coronary blood flow and cardiac output were increased while LVEDP and T were decreased. Studies on LV pressure-volume relation showed that Tet can markedly improve the LV compliance and the LV stiffness constant of LVH rat. These findings suggest that the regression of LVH in DOCA-salt hypertensive rats with Tet is associated with improvement of the contraction, relaxation and pump function, especially relaxation function and hemodynamics. PMID- 7785438 TI - [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6 keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. AB - Berberine (Ber) 20 mg.kg-1.d-1 for 1, 3, or 5 d inhibited platelet aggregation induced by ADP, arachidonic acid (AA) and collagen (Coll) in rats with 24 h reversible middle cerebral artery occlusion (MCAO), and the platelet adhesiveness was inhibited as well. Using radioimmunoassay method, the thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) contents in rat plasma were measured 24 h after MCAO. The results indicate that the TXB2 levels after drug treatment were lower than those in ischemia control rats, but the 6-keto-PGF1 alpha levels showed no obvious difference between the two groups. The same dose of Ber was also shown to inhibit thrombosis formation. This suggests that the decline of platelet aggregation and decrease of TXB2 content may be one of the important factors involved in the anti-cerebral ischemia effect of Ber. PMID- 7785439 TI - Demonstration of the potassium channel opening activity of GYKI-12743 by 86Rb+ efflux studies. AB - It has been demonstrated that the novel antihypertensive compounds GYKI-12743 showed a potassium channel opening effect as studied in rabbit ear arteries with 86Rb+ as K+ marker. GYKI-12743 produced a concentration dependent 86Rb+ efflux in the same concentration range as the well-known K(+)-channel openers, pinacidil and cromakalim. PMID- 7785440 TI - The combined cardiovascular effect of alcohol and noise in rats. AB - Groups of 20 CFY male rats were made to drink water containing 10% alcohol and 5% sugar or 5% sugar. Half of both groups (10-10 animals) were exposed to 95 dBAeq mixed industrial noise for 3 weeks, 6 hours daily. Haemodynamic measurements were carried out using isotope (57Co) labelled microspheres, which were repeated after the i.v. administration of 30 micrograms/kg/3 min noradrenaline, using a second isotope (113Sn). It was found, that alcohol decreased the cardiac fraction of the cardiac output, the nutritive blood flow of the myocardium and increased the vascular resistance of the adrenals. Noise decreased the lung fraction of the cardiac output and the hepatic blood flow. Interaction between noise and alcohol, inhibiting the effect of alcohol, was demonstrated on the intestinal blood flow, adrenal fraction of cardiac output and testicular vascular resistance. The haemodynamic effects of noradrenaline observed in the control were in several organs more or less modified in the animals treated with alcohol or noise or both. It was concluded that the exposures (alcohol, noise or both) modify the alpha-adrenergic effect of noradrenaline. PMID- 7785441 TI - Pharmacokinetic study on a new antiischaemic agent (BRLP-42). AB - In the present study the pharmacokinetics of BRLP-42--a new antiischaemic agent- was investigated in dogs and rats. Plasma concentrations were measured by HPLC. After intravenous application the curves can be characterized by a two compartment open pharmacokinetic model. The central volume of distribution (Vcentr.) is large (1.07 +/- 0.14 l/kg in dogs and 2.74 l/kg in rats), the first elimination half-life (t1/2 alpha) is 5.47 +/- 1.67 min in dogs and 13.7 min in rats. These facts indicate rapid and large tissue distribution. The excretion and/or metabolic elimination of BRLP-42 resulted in short second elimination half life (t1/2 beta = 41.45 +/- 2.34 min in dogs and 43.8 min in rats). After oral application high individual variability can be seen. This fact may be due to the different rate and/or extent of absorption process. The plasma level curves can be characterized by a one-compartment open pharmacokinetic model. The absorption seems to conceal the distribution phase of the kinetic curve. The absorption half life was short (t1/2a = 17.36 +/- 5.90 min in dogs and 2.7 min in rats). The bioavailability was 40 +/- 8% in dogs and 28% in rats. The elimination half-life (t1/2e = 28.77 +/- 0.88 min in dogs and 30.1 min in rats) is connected dominantly with metabolic elimination and/or excretion of BRLP-42. In the cases of intravenous as well as oral administrations the plasma concentrations decreased under the limit of quantitation by 4-6 hours in dogs and 4 hours in rats after treatments. PMID- 7785442 TI - Adaptive control in drug therapy. AB - In medical practice, drugs are administered with the goal of attaining a therapeutic effect without exceeding predetermined safety limits on any adverse action. This paper is intended to provide an introduction to pharmacokinetic model based adaptive control of drug levels that can be of use in achieving such therapeutic objectives. The principles are illustrated by the problem of providing rapid relief of acute asthmatic symptoms by infusing theophylline. PMID- 7785443 TI - Administration of benzpyrene and allylestrenol in fetal or neonatal periods of life: does it make difference in the microsomal activity? AB - Administration of allylestrenol or benzpyrene in fetal and neonatal periods of life make the rats susceptible to phenobarbiturate induction. Changes to controls could be observed in three of the enzyme activities tested (p-nitrophenol hydroxylase, cytochrome P450 and aniline-hydroxylase), with a dominance of the p nitrophenol-hydroxylase among them. There seemed to be no difference in the action of allylestrenol and benzpyrene, although treatment protocol in the neonatal period proved to be more effective. PMID- 7785444 TI - Changes in binding of monoclonal antibodies to TSH receptor following thyrotropin (TSH) and gonadotropin (GTH) pretreatments (studies on human thyroid and CHO cell lines). AB - Monoclonal antibody to TSH-receptor binds to the cells of human thyroid gland and to Chinese hamster ovary cell cultures. Pretreatments with TSH can decrease the binding of antibody, which effect is more expressed in CHO than in thyroid cells. Gonadotropin (FSH + LH) cannot influence the binding of antibody to thyroid, but there is an effect on CHO cells. Endotoxin (lipopolysaccharide, LPS) can depress the binding of antibodies on both objects and abolishes the difference between thyrotropin and gonadotropin receptors in their binding capacity, on both cell types. The experiments prove the similarity of thyrotropin and gonadotropin receptors which is responsible for the hormonal overlap. PMID- 7785445 TI - LB-145 a new radioactive isotope eliminating product with high selectivity. AB - LB-145 is a macrocyclic ligand, which forms, 200 times more stable complex with Stroncium (Sr) ions, than with calcium ones. The product is not toxic, it has no effect on circulation, respiratory system. 85,90Sr and 144Ce were given oral, i.p., s.c. or by inhalation, LB-145 either prophylactic or 30 (60) minutes after the radiointoxication i.v. or i.p. to the animals. The isotope contents of the organism were measured by whole body autoradiography, liquid scintillation, or by NK 350 ratemeter. One injection given prophylactic inhibited the incorporation of isotopes into the organism, within 24 hours after radiointoxication 75-80% of the isotopes were excreted by urine and faeces on the first day, 90-95% excreted on the first week. Also the isotope contents of femur and scissors were mobilised. The suggested human dose-0.5 g/70 kg bw-can be life-saving antihavaric injection. PMID- 7785446 TI - Methodological aspects in the studies on the mechanism of action of synthetic direct thrombin antagonists. AB - Requirements reported for an ideal anticoagulant [12] and for an ideal antithrombotic [18] show the necessity of many-sided methodological approach in order to detect the molecular mechanism of action of a novel synthetic antagonist of thrombin. The lack of a protocol internationally accepted, on the one hand, and with regard to a general proposal accepted [16], on the other hand, authors applied a complex methodological system involving also the study on the possible interactions at molecular level of some novel thrombin antagonists with the main components of their site of action. The surprising contradiction found between in vitro and in vivo efficacy of several antagonists could be attributed and explained by the significant differences in Ki and IC50 values determined in complex clotting assays containing plasma proteins and/or blood cells versus those measured in reaction mixtures consisting of a synthetic chromogenic substrate, the target enzyme, thrombin, and the antagonist compound in buffer solution. PMID- 7785447 TI - Three-dimensional (type I) microcrystals of detergent-solubilized membrane-bound gastric (H+, K+)-ATPase enzyme from hog and rabbit stomachs. AB - Multilamellar 3-dimensional (Type I) microcrystals of detergent-solubilized crude microsomes or purified protein preparations of membrane-bound gastric (H+, K+) ATPase from rabbit or hog stomachs develop in media consisting of 0.1 M KCl, 20 mM imidazole, 5 mM MgCl2, 3 mM NaN3, 5 mM DTT, 25 IU/ml Trasylol, 2 micrograms/ml DTBpC and 20-40% glycerol, using nonionic detergent of C12E8 or BRIJ 36 for solubilization. Crystals developed in a pH-range of 6.0-7.25, during 3-10 days of incubation, at 2 degrees C. For C12E8, the most effective detergent:protein ratio for crystallization varied between (1.8-2.0):1 for the microsomes and between (0.25-0.75):1 for the purified preparations. The results of biochemical and structural analysis of the (H+, K+)-ATPase crystals showed close resemblance to those of the sarcoplasmic reticulum Ca(2+)-ATPase from skeletal muscle and plasmamembrane (Na+, K+)-ATPase from kidney (J. Biol. Chem., 269, 10107-111, 1994). Based on these identities and the high (62%) overall sequential homology to the (Na+, K+)-ATPase, we conclude that the new crystals of the (H+, K+)-ATPase could also contain only the alpha-chain of the alpha beta heterodimers found in the native membrane. High-resolution electron microscopy of frozen-hydrated crystalline (H+, K+)-ATPase samples are in progress to give unit cell dimensions and molecular packing of the new crystals. PMID- 7785448 TI - Post-implantation fasting does not induce pregnancy failure in newly inseminated mice. AB - The effect of food deprivation on the rate of pregnancy failure in newly inseminated mice was evaluated. The pre-implantation fasting for 48 h beginning on day 4 or 5 postcoitum induced a high rate of pregnancy failure in newly inseminated females. However, fasting for 48 h on day 6 had a moderate effect in inducing pregnancy failure. By contrast, females which were deprived of food on day 7 postcoitum exhibited a significant reduction in the rate of pregnancy failure. Pre-implantation fasting was highly effective in inducing pregnancy failure compared to that of post-implantation fasting. The results suggest that fasting (i.e. day 4 or 5 postcoitum)--induced depression in prolactin has resulted in failure of pregnancy and fasting at post-implantation period (i.e. day 6 or after postcoitum) has not been interfered with progesterone production by placenta. PMID- 7785449 TI - Bradykinin-induced shifts in microhemodynamics, lymph production and flow in cat intestine; the effect of gut denervation. AB - In experiments on anaesthetized cats increased doses of bradykinin were administered intraarterially into an innervated part of the small intestine perfused in situ with constant inflow. It is concluded that the main factor accelerating transcapillary fluid efflux and lymph flow in this region with bradykinin is the rise in permeability of gut capillaries. This is confirmed by elevation in capillary filtration coefficient which takes place on the background of an increase in capillary hydrostatic pressure (when the intestine is naturally blood supplied), as decrease in the latter (when the preparation is perfused under constant inflow). The gut denervation decreasing regional vascular tone modifies bradykinin-induced lymph flow and shifts of hemodynamics in the small intestine. In denervated small intestine when compared with innervated ones bradykinin causes less expressed increase in lymph production and capillary hydrostatic pressure, but more marked elevation in capillary filtration coefficient. PMID- 7785450 TI - O2 transport in hypoxic albino rats of first and second generation. AB - The generations of rats raised in normobaric hypoxia (10% O2 in N2) were observed for changes in their oxygen-hemoglobin affinity, hemoglobin content (Hb) blood O2 capacity and pO2-O2 content curves: the first generation (H1) and the second generation (H2). H1 rats possessed a lower O2-Hb affinity while H2 rats had a higher O2-Hb affinity than normoxic control rats. Hb was greater in both hypoxic groups, however, H2 rats showed a Hb lower than that of H1 rats. Both hypoxic groups showed a leftward shift of the pO2-O2 content curve. In pO2 range between 25 and 50 mmHg, H2 rats showed a shift greater than H1 rats. So in hypoxic conditions the H1 rat's ability to supply enough O2 to the tissues is smaller than that of H2 rats. In the rat's adaptation to hypoxia the Hb increase plays only a minor role while O2-Hb affinity increase constitutes a physiologically meaningful adaptation. PMID- 7785451 TI - Protein level in testes, kidneys and liver after AET or MEA treatment of mice. AB - The adult male Swiss mice were treated intraperitoneally with AET (2 aminoethylisothiouronium Br.HBr) or MEA (cysteamine HCl), in a toxic dose of 400 mg/kg body weight. The measurements of the protein content in crude homogenates of testes, kidneys and liver were done every fourth hour throughout a 24-hour period. Treatment of mice with AET and MEA resulted in different patterns of temporal changes in the protein content in testes, kidneys and liver expressed in mg per 1 g of fresh tissue and per the whole organ weight. The extent and timing of the alterations in the protein level appeared to depend on the particular organ chosen and the thiol agent applied. PMID- 7785452 TI - Changes in the mast cell number and degranulation pattern during periovulatory period and after blocking gonadotrophin surge in mice ovarian compartments. AB - Mast cell in the ovary of cyclic mice were observed in the ovarian medulla, hilum and bursa, but not in the cortex. A significant increase in the degranulation of mast cells was observed in the hilum and bursa but not in the medulla following the gonadotrophin (Gn) surge as compared with before the surge at proestrus. The results of pentobarbital treatment at proestrus imply the significant role played by estradiol 17-beta (E2) in inducing mast cells migration and degranulation, specially in the medullary, cortical and bursal region of the ovary. The results indicate differential regulation of mast cells number and degranulation in different ovarian compartments of mice. PMID- 7785453 TI - Ultrasound velocity, through bone predicts incident vertebral deformity. AB - We followed 130 postmenopausal women without evidence of vertebral deformity by lateral spine radiographs on entry into study for 2 years, and repeat spine radiographs were taken at the end of that time. Incident deformities occurring within this 2 year period were detected by two methods, a level-specific radiogrammetric approach and visual inspection by skilled clinicians. Fourteen incident deformities were detected by the radiogrammetric method, and 19 by the clinicians. Ultrasound transmission velocity was measured at the patella in each subject on entry. Values for ultrasound velocity were significantly correlated with incident fracture occurrence, with individuals having velocity values more than one standard deviation below the mean for the group exhibiting from 3.3 to 4.6 times the probability of incident fracture as individuals with velocity values more than one standard deviation above the mean. Thus, low values for ultrasound transmission velocity at the patella detect yet-unexpressed bony fragility at the spine and predict future fracture. PMID- 7785454 TI - Comparison of speed of sound ultrasound with single photon absorptiometry for determining fracture odds ratios. AB - The purpose of this study was to compare the ability of ultrasound velocity measurement with that of single photon absorptiometry to determine the odds of history of fracture since age 40, for a population-based study. To do this we computed odds ratios and 95% confidence intervals for 809 women and 502 men, aged 50 years and older, who are participants in the prospective phase of the Saunders County Bone Quality Study. These participants received both the ultrasound and single photon absorptiometry bone measurements at the initiation of the study. In addition, a history of all fractures that had occurred to participants since age 40 was obtained. The two bone assessment methods were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals to show which estimate of odds ratio is the most precise. Ultrasound velocity estimates a higher probability of odds of both low-trauma fractures and all fractures than distal radius and ulna bone mineral content, but lower than bone mineral density at the same sites for both women and men. However, the ultrasound measure is more precise than bone mineral density, but less precise than bone mineral content. We conclude that ultrasound velocity is as good as single photon absorptiometry in estimating odds of fracture. PMID- 7785455 TI - Quantitative ultrasound and vertebral fracture in postmenopausal women. Fracture Intervention Trial Research Group. AB - Quantitative ultrasound is a promising technique to evaluate fracture risk. To test the hypothesis that reduction of one ultrasound measurement, broadband ultrasound attenuation (BUA), is associated with an increased risk of vertebral fracture in postmenopausal women, we performed a cross-sectional analysis of 442 women aged 55-80 years enrolling in a clinical trial of alendronate. Prior to randomization, we obtained bone mineral density (BMD) measurements of the hip, spine, and whole body, radiographs of lateral lumbar and thoracic spine, and duplicate measurements of calcaneal BUA with a Walker Sonix UBA575. Vertebral fractures were defined by morphometry and semiquantitative reading by a radiologist. After adjustment for potential confounders, the relative risk of vertebral fracture was 1.8 (95% CI 1.4-2.3) for each standard deviation reduction in BUA; for each standard deviation reduction in BMD, the relative risk was 1.7 (95% CI 1.3-2.1) at the femoral neck, and 2.2 (95% CI 1.7-2.9) at the spine. Adjustment for hip, spine, or whole body BMD did not significantly alter the relation between BUA and vertebral fracture. For example, after adjusting for spine BMD, the relative risk of vertebral fracture was 1.5 (95% CI 1.1-2.0) for each standard deviation reduction in BUA. We conclude that low BUA is associated with the presence of vertebral fractures in postmenopausal women. The relation between BUA and vertebral fracture is similar to that observed for BMD and vertebral fractures. Furthermore, the relation between BUA and vertebral fracture persists after adjustment for BMD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785456 TI - Ethnic differences in bone density in female South African nurses. AB - In the United States, the higher prevalence of osteoporosis and the higher incidence of fractures in whites than in blacks may be attributed to the finding of lower bone density (BD) in both white children and adults. In South Africa, osteoporosis and fractures also occur more frequently in whites than in blacks. Appendicular BD has been found to be similar in black and white children in South Africa, but there is little information available on BD of adults in South Africa. This cross-sectional study aimed to assess changes in BD with age in adult females in South Africa and to assess possible differences in peak BD and in the rate of postmenopausal bone loss between blacks and whites. Data for 180 black and 184 white female nurses aged 20-64 years were analyzed. The distal radius bone density (RBD) was measured by single photon absorptiometry. The lumbar spine bone density (SBD) and the femur bone density (FBD) were measured by dual-energy X-ray absorptiometry. Blacks were shorter than whites (p = 0.0001), and blacks' weight, body mass index, and skinfold thickness increased with age. Peak SBD and RBD were similar in blacks and whites, but peak FBD was higher in blacks (p = 0.0001). This ethnic difference in peak FBD became apparent in the fourth decade. Peak FBD was similar in black and white subjects with normal body mass indices (p = 0.09), but in overweight subjects peak FBD was higher in blacks than in whites (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785457 TI - Sources of interracial variation in bone mineral density. AB - Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785458 TI - The relations between physical ability and bone mass in women aged over 65 years. AB - In this cross-sectional study of 55 women (mean age 73.54 +/- 5.87), the magnitude of the relation between different indices of physical ability and confounding factors to bone density were determined. Physical fitness was assessed by direct measurement of maximal oxygen consumption (VO2 max), isokinetic muscle strength, and quadriceps and psoas muscle surfaces and densities using computed tomography. Anthropometry, chronological and gynecological ages, and dietary calcium intake were also recorded. The bone mineral density (BMD) was evaluated at the axial level (lumbar spine and proximal femur) and at the peripheral level (radius and tibia, cancellous and cortical compartments). Parameters related to physical ability proved to be the best predictors of BMD in radial and tibial cancellous compartments, spine, femoral neck, and trochanter, accounting for 15-27.5% of the total variance. The VO2 max was a major determinant of the femoral mineral density and one of the predictors of radial and tibial cancellous compartments. Psoas parameters were strongly related to spine mineral density and also constituted a predictor of radius (cancellous) and tibia mineral densities. The arm muscle strength could predict, though weakly, the BMD of axial skeleton, whereas thigh muscle strength only predicted the BMD of inferior limbs. No correlation was observed between current dietary calcium intake and BMD. Age-postmenopause and fertile life remained predictive of BMD at mostly cancellous sites, whereas anthropometry exerted important effects on radial and tibial cortices. The study suggests distinct sets of relations between physical ability and the BMD variables. Subjects with greater and denser psoas muscles had greater spine BMD, and those with higher VO2 max had greater proximal femur BMD. PMID- 7785459 TI - Bone density in young women is associated with body weight and muscle strength but not dietary intakes. AB - Potential determinants of bone mineral density (BMD) were studied cross sectionally in 115 healthy, sexually mature Caucasian women aged 18 years. Bone mineral density (Hologic QDR1000W) of the lumbar spine, proximal femur (five sites), and distal tibia and fibula; fasting blood and urine calcium biochemistry; serum sex hormone levels (follicular phase); nutrient intakes; aerobic fitness; trunk muscle strength; and habitual activity levels were measured. The effects of heredity were considered by measuring the BMD of 107 of the subjects' mothers. Simple and stepwise regression analysis were used to identify significant determinants of BMD at each of the regions studied. The analysis indicated that significant bivariate correlations exist between BMD at all sites and body weight (r = 0.23-0.47, p < or = 0.01), lean body weight (r = 0.34-0.46), trunk strength (r = 0.27-0.47), physical activity score (r = 0.20 0.25), and aerobic fitness (r = 0.29-0.45). Dietary calcium intake correlated significantly with BMD at the trochanter site only (r = 0.19), and none of the biochemical or hormonal indices measured correlated consistently with BMD at any site. Significant correlations between the BMD of mothers and daughters ranged from r = 0.43 at lumbar spine to r = 0.34 at the intertrochanteric site. Paired t tests showed the daughters had significantly (p < 0.03) lower BMD than their mothers at the lumbar spine (98 +/- 12% [mean +/- SD]) and significantly higher (p < 0.002) BMD at the femoral neck, trochanter, and total hip sites (110 +/- 16%, 108 +/- 17%, 103 +/- 14%, respectively). When stepwise regression analysis included weight-corrected strength of the trunk flexor muscles (Corr Flex), weight-corrected aerobic fitness (Corr VO2max), physical activity score, and body weight, body weight was the only significant determinant of BMD at all sites. Corr Flex made significant contributions at all sites except the femoral neck, while Corr VO2max made additional contribution at the femoral neck, trochanter, total hip, and shaft of femur sites. These variables accounted for 13-27% of the variance in BMD. The addition of mother's BMD to these independent variables, in stepwise regression analysis, improved the prediction to 18-31% of the variance. PMID- 7785460 TI - Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria. AB - A new slow-release, neutral potassium phosphate salt (UroPhos-K) has been formulated in order to minimize gastrointestinal side effects and avoid sodium induced calciuria. It was tested in a prospective randomized, double-blind trial in a group of 21 kidney stone patients with absorptive hypercalciuria type I (AH). Twelve patients allocated to the UroPhos-K group received four tablets twice daily with breakfast and an evening snack providing 1240 mg of phosphorus and 63.5 mEq of potassium daily. Nine patients assigned to the placebo group received placebo tablets of the same appearance containing excipient only. Subjects were studied during a 3-day period in the hospital while consuming a constant metabolic diet containing 400 mg Ca, 100 mEq Na, and 800 mg P per day before and after 3 months of treatment. Treatment with UroPhos-K did not cause any significant gastrointestinal side effects; nor did it raise fasting serum K or phosphorus, or reduce hemoglobin or creatinine clearance. It was associated with a rise in urinary K from 46 +/- 7 to 98 +/- 9 mEq per day and phosphorus from 744 +/- 185 to 1535 +/- 112 mg per day (p < 0.001 each). UroPhos-K treatment reduced urinary Ca from 288 +/- 63 to 171 +/- 49 mg/day (p < 0.001), without altering oxalate excretion. It reduced the urinary saturation of calcium oxalate without altering that of brushite. Moreover, by increasing urinary excretion of inhibitors (citrate and pyrophosphate), it reduced the propensity for spontaneous nucleation of brushite (increased formation product of brushite) and inhibited crystal agglomeration of calcium oxalate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785461 TI - Expression of bone morphogenetic protein-6 messenger RNA in bovine growth plate chondrocytes of different size. AB - Bone morphogenetic protein-6 (BMP-6) is an osteoinductive factor that may have a regulatory role in the terminal differentiation of chondrocytes. We investigated the expression of BMP-6 messenger RNA in freshly isolated newborn calf rib chondrocytes separated by density gradient centrifugation into five highly enriched subpopulations at different stages of maturation as assessed by cell size and alkaline phosphatase activity. Expression of BMP-6 mRNA was compared with expression of type II collagen mRNA and type X collagen mRNA using Northern analysis. Type X collagen mRNA expression increased with increasing cell size whereas type II collagen mRNA varied little with cell size. BMP-6 mRNA expression was highest in small cells and lowest in the largest cells, which were maximally expressing type X collagen mRNA. This suggests that up-regulation of the BMP-6 gene may precede chondrocyte hypertrophy. PMID- 7785462 TI - Autoregulation of inducible prostaglandin G/H synthase in osteoblastic cells by prostaglandins. AB - Prostaglandins (PGs) have been postulated to amplify their own production by stimulating cyclic adenosine monophosphate activity, which in turn stimulates PG production. We examined regulation of messenger RNA levels for the inducible and constitutive prostaglandin G/H synthases, PGHS-2 and PGHS-1, in murine osteoblastic MC3T3-E1 cells, which express both PGHS-1 and PGHS-2, and in rat osteoblastic Py1a cells, which express only PGHS-2. Prostaglandins E2, F2 alpha, and D2 induced PGHS-2 mRNA in both cell lines under serum-free conditions and stimulated small increases in PGHS-1 mRNA levels in MC3T3-E1 cells. PGE2 (1 microM) increased the transcription rate of PGHS-2 mRNA 9-fold at 2 h in serum free cells and also induced PGHS-2 protein. In the presence of arachidonic acid or serum, PGs also increased medium PGE2. Both forskolin, a protein kinase A activator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, have previously been shown to induce PGHS-2 mRNA in MC3T3-E1 cells, but in the present study only PMA induced PGHS-2 expression in Py1a cells. The induction of PGHS-2 mRNA in Py1a cells by PGs was inhibited by chelerythrine, a PKC inhibitor, and blocked by 24 h of pretreatment with PMA. The 2 h serum stimulation of PGHS-2 mRNA in MC3T3-E1 cells was inhibited 40-50% by three structurally unrelated nonsteroidal anti-inflammatory drugs (NSAIDs), suggesting that endogenous PGs also amplify PG production through induction of PGHS 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785464 TI - Effect of 1,25-dihydroxyvitamin D3 treatment on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice. AB - Bone cells isolated from the Hyp mouse, the murine homologue for hypophosphatemic vitamin D-resistant rickets, produce abnormal bone when transplanted to either normal or phosphate-supplemented Hyp mice. To assess whether correction of the bone formation by mutant cells transplanted into either normal or Hyp mice could be achieved in the presence of supraphysiologic serum concentrations of 1.25 dihydroxyvitamin D3 (1.25-(OH)2D3), recipient mice of both genotypes were infused continuously with 1.25-(OH)2D3 (0.2 micrograms/kg/day). Bone nodules present in transplants recovered after 14 days were characterized by measuring the osteoid thickness and volume. Administration of 1.25-(OH)2D3 to Hyp mice corrected the defective bone formation by normal cells but not by pair-transplanted Hyp cells, despite normalization of serum phosphate levels and 3-fold increases in serum 1.25-(OH)2D3. The osteoid thickness and volume in Hyp transplants into 1.25 (OH)2D3-treated Hyp mice were, however, markedly reduced down to values observed for Hyp transplants into recipient normal mice. Administration of 1.25-(OH)2D3 to normal mice improved further bone formation by mutant cells without affecting that by pair-transplanted normal cells. Administration of 24.25-(OH)2D3 (1 microgram/kg/day) combined with 1.25-(OH)2D3 to recipient mice of both genotypes prevented the sharp fall in serum 24.25-(OH)2D3 but was not more beneficial than 1.25-(OH)2D3 alone for improving bone formation by transplanted Hyp cells. These observations demonstrate an abnormal response of the mutant cells to the extracellular environment and support the concept of an intrinsic osteoblast defect in the Hyp mouse. PMID- 7785463 TI - Rat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic differentiation of bone marrow stromal cells. AB - We previously reported that bone marrow stromal cells produce insulin-like growth factors (IGF-I and -II), and that medium conditioned by marrow stromal cells stimulates osteoblast proliferation in vitro. The present study employed the rat tail-suspension model to unload the hindlimbs. It was designed to test the hypothesis that the development of osteopenia or osteoporosis could be due to a deficit in the osteogenic function of marrow stromal cells. Although tail suspension suppressed body weight during the first 3 days of an 11-day pair-fed study, the overall weight gain recorded by these animals was normal. Nevertheless, bone growth was inhibited by suspension. Similarly, the total adherent marrow stromal cell population harvested from the femurs and tibias was decreased by tail suspension, and only half the normal number of fibroblastic stromal cell colonies grew when they were cultured. The proliferation of alkaline phosphatase-positive cells in the stroma was also inhibited. Northern hybridization revealed that the messenger RNA level for transforming growth factor-beta 2 and IGF-II in stromal cell was reduced by tail suspension. The production of IGF-II by marrow stromal cells was also decreased. The steady-state level of five different transcript sizes of IGF-I mRNA was altered differentially by tail suspension. Osteopontin mRNA was also reduced in marrow stromal cells from tail-suspended rats compared with the normal rats. These data suggest that skeletal unloading not only alters the mRNA level for growth factors and peptide production, but also affects the proliferation and osteogenic differentiation of marrow stromal cells. These changes may be responsible for the reduced bone formation in osteopenia and osteoporosis. PMID- 7785465 TI - Upper extremity bone mass and osteoarthritis of the knees: data from the Baltimore Longitudinal Study of Aging. AB - To examine the association of upper extremity bone mass with osteoarthritis (OA) of the knee, bilateral standing knee radiographs, taken between 1985 and 1991, in 430 Caucasian male and 266 Caucasian female subjects aged 40 years and above in the Baltimore Longitudinal Study of Aging, were read by one investigator for grade of OA using Kellgren-Lawrence scales. Several measures of upper extremity bone mass, size, and density, including combined cortical thickness (CCT), total width and percentage of cortical area of the second metacarpal, and bone mineral content (BMC), width, and density of the distal third of the left radius measured with single photon absorptiometry, were assessed at the same visit. In univariate analyses, men and women with definite knee OA were significantly older, men had significantly greater radial width, and women had significantly lower bone mass as measured by both CCT and BMC. After adjustment for age and body weight, however, men with knee OA had significantly higher BMC and radial width while neither of these measures of upper extremity bone mass and size was significantly associated with the presence of definite knee OA in women. Neither measure of upper extremity bone density was significantly associated with definite knee OA in either sex. These data suggest that, although men (but not women) with definite knee OA have significantly higher levels of adjusted radial bone mass and size, subjects with knee OA do not have significantly higher levels of adjusted bone mineral density at either upper extremity site. PMID- 7785467 TI - Zinc is a potent inhibitor of osteoclastic bone resorption in vitro. AB - It is well established that zinc, an essential trace element, plays an important role in growth and stimulates bone formation. However, the effects of zinc on bone resorption have received little attention. We studied its effects on isolated rat osteoclasts. Unexpectedly, osteoclasts were exquisitely sensitive to zinc, with a significant decrease in bone resorption occurring at concentrations as low as 10(-14) M. This effect was specific for zinc and was not observed with the other transitional or alkaline metals studied. There was no evidence of toxicity at concentrations up to 10(-4) M. Zinc also completely abolished the stimulatory effect of parathyroid hormone. Zinc is therefore a highly potent and selective inhibitor of osteoclastic bone resorption in vitro. The mode of action remains to be established and may represent a novel inhibitory mechanism in the osteoclast. PMID- 7785466 TI - Regulation of parathyroid hormone messenger RNA levels by protein kinase A and C in bovine parathyroid cells. AB - Secretion of parathyroid hormone (PTH) is regulated by Ca2+ as well as by protein kinases A and C. In this study we report that protein kinases A and C regulate PTH messenger RNA levels in vitro in dispersed bovine parathyroid cells. Incubation of bovine parathyroid cells with cholera toxin (10(-9) M), which activates adenylate cyclase and indirectly stimulates protein kinase A, increased PTH mRNA levels about 2-fold after 3 and 7 h incubation, but not at 24 h. Incubation with pertussis toxin (5 x 10(-9) M), which blocks the high-calcium mediated inhibition of cyclic adenosine monophosphate accumulation in these cells, also reversed the inhibition of PTH mRNA levels at high Ca2+ (2.0 mM) with a marked increase in PTH mRNA levels. Pertussis toxin also increased PTH mRNA at a low extracellular Ca2+ concentration (0.7 mM) (4-fold increase) and a normal concentration (1.25 mM) (2-fold increase). Inhibition of protein kinase C both by staurosporine (1 x 10(-8) M) and by prolonged incubation with the phorbol ester phorbol 12-myristate 13-acetate (PMA) (1 x 10(-7) M), decreased PTH mRNA levels at 24 h, reaching approximately 40% and 5% of control, respectively. Staurosporine and PMA had no effect on PTH mRNA levels at 3 h. The inactive phorbol ester, phorbol 12-13-dibutyrate (PDBu), had no effect on PTH mRNA levels at 1 and 24 h. There were no changes in a control gene 18S RNA in these studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785469 TI - Relations between histologic indices of bone formation: implications for the pathogenesis of spinal osteoporosis. AB - Wall thickness, a major determinant of trabecular thickness, falls with age and falls further in osteoporosis. To estimate the importance of defective osteoblast recruitment in the pathogenesis of this defect, we compared various histologic indices of bone formation in iliac bone biopsies in three groups of subjects- healthy premenopausal women, healthy postmenopausal women, and patients with postmenopausal osteoporosis and at least one non-traumatic vertebral compression fracture. Indices that reflect the frequency of activation of bone remodeling and consequent birth rate of new teams of osteoblasts (osteoid surface, mineralizing surface, osteoblast surface, and bone formation rate, all expressed per unit of bone surface) were each higher in healthy subjects who were postmenopausal than in those who were premenopausal, but lower in osteoporotic than in normal postmenopausal women. In each group, the primary surface measurements were significantly correlated with each other, but the correlation was less close in those with osteoporosis. Indices that reflect the average collective performance of individual teams of osteoblasts (mineralizing surface and osteoblast surface per unit of osteoid surface, mineral apposition rate, adjusted apposition rate, and wall thickness) were all lower in postmenopausal than in premenopausal normal subjects, and even lower in those with postmenopausal osteoporosis. The parameters of the regression lines relating bone formation rate to osteoblast surface were essentially the same in each group, indicating that bone formation rate per unit of osteoblast surface was unaffected by age or menopause, and was the same in osteoporosis as in healthy subjects of similar age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785468 TI - Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. AB - Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785470 TI - Bone marrow cells are targets for the anabolic actions of prostaglandin E2 on bone: induction of a transition from nonadherent to adherent osteoblast precursors. AB - Although prostaglandin E2 (PGE2) is known to stimulate bone formation in vivo, its mechanism of action is not well understood. Circumstantial evidence suggests that bone marrow cells (BMC) may well be involved in this, and in order to investigate this further we have studied the effect of PGE2 on proliferation and matrix synthesis in high-density BMC cultures and on colony-forming unit (CFU-f) formation efficiency by BMC in vitro. High-density cultures of BMC formed a collagenous, calcified matrix, synthesized osteocalcin and expressed alkaline phosphatase activity. The addition of PGE2 caused a concentration-dependent increase in total (but not specific) APase activity, cell number, and collagen accumulation. It was found that PGE2 need only be present during the first 48 hours of the culture period and that longer exposure had no additional effect. PGE2 also caused a concentration-dependent increase in CFU-f formation, and it was found that this was due to the recruitment of new mesenchymal precursor cells from the nonadherent fraction of the BMC. Once again, the presence of PGE2 for only the first 48 hours of the culture period was enough to precipitate a maximal response. We conclude that one mechanism for the anabolic actions of PGE2 may be the recruitment of OB precursors from a population of nonadherent mesenchymal precursor cells present in the bone marrow. PMID- 7785471 TI - Morphologic stages in lamellar bone formation stimulated by a potent mechanical stimulus. AB - The temporal stages of lamellar bone formation were studied using an animal model subject to up to 16 weeks of a controlled, externally applied load. The left ulnae of 15 adult male turkeys were functionally isolated via transverse metaphyseal osteotomies, while transcutaneous Steinmann pins permitted in vivo loading of the preparation via a servo-hydraulic actuator. For 5 days per week, the ulnae were exposed to 100 cycles per day of an applied load sufficient to cause a peak strain normal to the bone's longitudinal axis of 2000 microstrain (mu E). The contralateral limb was left surgically undisturbed and served as a baseline control. Following a loading period of 4, 8 or 16 weeks, ulnae were harvested and prepared for quantitative bone histomorphometry. Compared with each animal's contralateral ulna, the area of the experimental ulnae increased by 12.5% (+/- 5.6%) at 16 weeks. Periosteal mineral apposition rates in the loaded ulnae were significantly increased compared with control values, with a maximum rate of 6.0 +/- 3.4 microns/day at 5 weeks, slowing to 2.0 +/- 0.3 microns/day by 15 weeks. At 16 weeks, new bone was composed of primary and secondary osteons as well as circumferential lamellae, with osteocyte density and organization indistinguishable from that of the original cortex. Remnants of the initial woven bone response seen at 4 weeks remained clearly visible at both 8 and 16 weeks as diffusely labeled interstitial elements within the newly formed lamellar construct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785473 TI - Hip axis length and osteoporotic fractures. Study of Osteoporotic Fractures Research Group. PMID- 7785472 TI - Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats. AB - The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6 month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1 38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans. PMID- 7785475 TI - The relationship between gender, symptoms of bulimia, and tolerance for stress. AB - University students completed a questionnaire that included a measure of bulimia and a measure of tolerance for stress. Women reported significantly more symptoms of bulimia and a lower tolerance for stress than did men. Women in their first year on campus reported significantly more symptoms of bulimia than those not in their first year. For both women and men, a greater number of bulimic symptoms was associated with lower levels of stress tolerance. The present results suggest that women in their first year on campus should be targeted in intervention and prevention activities for eating disorders and that the relationship between disordered eating and stress is the same for both women and men. PMID- 7785474 TI - Evaluating multiple outcomes and gender differences in alcoholism treatment. AB - This study followed 592 alcoholics (180 women and 412 men) after discharge from inpatient treatment. Multiple measures of treatment outcome were used to broaden our understanding of the process of recovery from alcohol abuse, and how that process differs for men and women. Patients were interviewed by telephone between 3 and 15 months after discharge to gather information about post-treatment experiences including: relationship with family, role performance, psychological impairment, and effort toward recovery. Additionally, if any alcohol use took place after treatment, information was collected about the pattern of alcohol consumption. Results indicated being married is consistently related to less drinking for men, while for women, being married contributes to relapse in the short term. The determinants of each measure of outcome were different for women and men, indicating that the process of recovery is not the same for both genders. The study confirms that drinking is related to other adverse outcomes for men, but not necessarily for women. It is evidence that women and men have different post-treatment functioning, and that different characteristics are predictive of these outcomes. PMID- 7785476 TI - Pretreatment dropout as a function of treatment delay and client variables. AB - Utilizing a retrospective analysis we examined factors correlated with preintake dropout in patients phoning to make intake appointments for cocaine treatment. Inquiries of 235 individuals calling our outpatient cocaine treatment program over a 7-month period were analyzed for relationships between patient age and gender; residence in the city where the program is located; marital status; referral source; reported problems with alcohol, marijuana, and heroin; reported last use of cocaine or other illicit stimulants; assigned counselor gender; person who made the appointment; days to the intake appointment; and attending the scheduled intake session. Only days to appointment was significantly (Wald = 12.4587, df = 1, p < .05 and chi 2 = 17.7, df = 8, p < .05) correlated with attending the scheduled intake session. Appointments scheduled the same day differed significantly (chi 2 = 4.3, n = 235, df = 1, p < .05) from appointments scheduled later. This suggests that client and situational variables are not significantly related to initial attendance and enhances the significance of systemic variables that are under a clinic's control, such as appointment delay. The results indicate that the longer the delay between the initial phone contact and the scheduled appointment, the less likely a client is to attend an appointment. Further, they suggest that the greatest decrease in initial attendance occurs in the first 24 hours following the phone inquiry. Taking a "microscopic" look at the appointment delay variable is valuable in understanding and addressing preintake dropout. PMID- 7785477 TI - Participation in a parent training program for methadone clients. AB - Programs for drug abusers are plagued by high rates of dropout. Because of the strong relationship between longer treatment and positive outcome, researchers have begun to study individual and program-specific factors that influence premature termination of treatment. For the most part, these studies have focused on dichotomous measures of dropout or number of sessions attended. In this article, we extend this line of research in two ways. First, we develop and measure a number of indicators of treatment participation based on therapist ratings. Second, we develop a model of treatment participation that employs both individual and program-specific factors. The data show that tremendous variation in participation occurred even among those who attended a majority of sessions, which highlights the importance of obtaining more elaborate measures of treatment participation. The model predicting treatment participation suggests that initiation of heroin use later in life, continued use of marijuana, and behavioral indicators of motivation are the strongest predictors of program participation. Research and practical implications of the findings are discussed. PMID- 7785478 TI - Influence of family disharmony and parental alcohol use on adolescent social skills, self-efficacy, and alcohol use. AB - Deficits in social skills have been found to be related to adolescent substance use. Little effort has been devoted to understanding how family factors influence the acquisition of these skills. This study examined the manner in which family disharmony and parental alcohol use affect adolescent alcohol use through their influence on the acquisition of social skills and self-efficacy regarding one's ability to utilize these skills. It was hypothesized that family disharmony and parental alcohol use directly influenced usage and affected usage indirectly through their influence on acquisition of social skills. Social skills were also hypothesized to affect usage directly and to affect usage indirectly by influencing beliefs regarding one's ability to implement these skills. Results indicated that family disharmony was directly related to adolescent alcohol use and social skills. Parental alcohol use was related only to adolescent usages, not to social skills. Social skills were related to self-efficacy, which was related to alcohol use but was not directly related to usage. Results are discussed in terms of the importance of family influences on adolescent alcohol use, the importance of including families in prevention efforts, and the importance of the acquisition of self-efficacy relative to social skills. PMID- 7785479 TI - MMPI performance among women with bulimia: a cluster-analytic study. AB - Forty-two women, meeting criteria for bulimia, completed the MMPI. Cluster analysis of their scores revealed two distinct profile types. The first cluster, comprising about 64% of subjects, produced a mean profile in which only the Pd scale exceeded a t score of 70. In contrast, about 36% of subjects yielded a cluster-derived mean profile that was significantly elevated on many scales, including Pd, D, Pt, and Sc. The existence of these two very different subgroups of women with bulimia replicates previous work in this area and has potentially important implications for the description, treatment, and general understanding of those with this condition. PMID- 7785480 TI - An empirical classification of drinking patterns among alcoholics: binge, episodic, sporadic, and steady. AB - Steady (daily, continuous) versus nonsteady (binge, episodic, bout, intermittent) drinking pattern have been influential Jellinek's (1960) formulation of delta and gamma drinkers, and are used as variables in various typological systems and drinker profiles. However, definitions of drinking patterns vary widely across studies, and most studies rely on one self-report item to establish a subject's pattern. To systematize and empirically test drinking-pattern schemas, we developed detailed definitions of binge, episodic, sporadic, and steady drinking patterns. A computer algorithm was written in SAS to classify 94 male alcoholics participating in outpatient conjoint therapy, using 6-month pretreatment drinking data from the Timeline Followback Interview. The final classification was: 3 (3%) binge, 33 (35%) episodic, 12 (13%) sporadic, and 40 (43%) steady drinkers. Six (6%) were unclassifiable (due to too few drinking days or too many interruptions to the pattern) by the computer. Episodic, sporadic, and steady drinkers did not differ in demographics, alcohol-related consequences, global psychological distress, or marital satisfaction. Steady drinking was associated with later onset of drinking problems (> 25), while episodic and sporadic drinking were associated with earlier onset. These results are contrary to current use of "binge drinking" as a variable associated with Type 1 alcoholism. Predictive validity analyses indicated that steady drinkers continued to drink more frequently than episodic and sporadic drinkers during treatment and 6 months posttreatment. Also, preliminary data indicate that pretreatment drinking pattern may be predictive of similar within-treatment urge-to-drink patterns. Implications for research and treatment are discussed. PMID- 7785481 TI - Vagal tone regulation during sustained attention in boys exposed to opiates in utero. AB - Attention and learning problems among children exposed to opiates in utero have been previously reported but are difficult to interpret due to imprecise measurement and inadequate control of postnatal factors. In this study, we used a behavior-based measure of attention (continuous-performance tasks) and a physiological index of sustained attention (cardiac vagal tone) to measure more precisely the process of sustained attention. Boys, aged 7 to 12, exposed to opiates in utero, were compared to boys whose mothers began using illicit substances after the child's birth (environmental controls), and boys whose mothers were non-drug users. This three-group design was intended to isolate in utero effects from postnatal environmental influences. Vagal tone, a measure of heart-rate variability sensitive to vagal influences on the heart, was measured pre- and postbaseline and during the three tasks of the Gordon Diagnostic System (Delay, Vigilance, and Distractibility). Vagal tone has been found to be sensitive to changes in environmental demand for sustained attention in infants, school-age children, and adults. Results indicated that when distractors were added to the vigilance task (Distractibility task), opiate-exposed boys failed to suppress vagal tone compared to both control groups. However, both the opiate exposed boys and the environmental controls made fewer correct responses than non drug-exposed controls on this task. These results indicate that normal physiological responses to increased attentional demand may be impaired in boys exposed in utero to opiates in this age range. However, the poor Distractibility scores of both the opiate-exposed and environmental controls suggests an important role of environmental influences on attentional performance. PMID- 7785483 TI - Eating style and symptoms of eating disorders: further explorations. AB - Based on earlier efforts to document relationships between eating styles involving hunger, deprivation, and restraint and symptoms of eating disorders, three scales--Eating Style, Feeling Deprived, and Dieting Style--were created and administered to 259 University females, 118 males, and 50 nonstudent females. Of interest were psychometric properties of the scales, their relationships to each other and with symptoms, beliefs about weight control, and body weight. One year later, findings based on Eating Style were replicated and extended in smaller groups of the original University subjects. Appreciable relationships occurred almost uniformly between Eating Style (addressing hunger, deprivation, and restraint) and proposed correlates. Feeling Deprived (a measure of avowed deprivation) correlated consistently with beliefs about weight control and weight variables, but not symptoms. Measurement of Dieting Style was hampered by small ns. PMID- 7785482 TI - Parent-child closeness affects the similarity of drinking levels between parents and their college-age children. AB - College males reported drinking more frequently and in higher amounts than females. Correlations between quantity-frequency (QF) indices of drinking by parents and by their college-age children showed the greatest similarity between fathers and sons. Log linear analyses compared each parent's drinking level against each of three other factors that might affect the QF levels of college age children: the relationship between parent and child, the effect of the parent's drinking on the parent, and how the parent's drinking affected their treatment of the child. The results supported models in which the relationship of each parent's drinking to the QF levels of both sons and daughters was affected by the closeness of the parent-child relationship. However, there was no support for models involving how each parent's drinking affected that parent or how each parent's drinking affected their treatment of the child. PMID- 7785484 TI - Childhood and adulthood temperament and problem behaviors and adulthood substance use. AB - A sample of 229 adult men and women were assessed to examine the relationships between childhood and adulthood temperament and problem behaviors. The influence of these variables on adult substance use was also assessed. Results indicated that individuals who had "difficult" temperament characteristics (e.g., hyperactivity) and who experienced problem behaviors (e.g., antisocial behaviors) as children were likely to exhibit them as adults. In addition, the continuation of temperament characteristics and problem behaviors from childhood into adulthood did not demonstrate a high degree of specificity. When the relationships between temperament and problem behaviors to substance use were examined, conduct disorder during childhood and antisocial behavior during adulthood were found to be the best predictors of adult substance abuse. Moreover, this relationship became increasingly stronger with more substance involvement. These results underscore the importance of examining substance use in finer detail by assessing the pattern of substance use, instead of overall substance use involvement. PMID- 7785486 TI - Alcohol consumption: biochemical and personality correlates in a college student population. AB - The frequency of alcohol use among a subject population of 28 male and 60 female college students was assessed using the Student Alcohol and Drug Use Survey (STADUS). Data were also collected on personality traits as measured by the Sensation Seeking Scale V (SSSV) and the Eysenck Personality Questionnaire (EPQ). Finally, three biochemical variables were assessed: monoamine oxidase (MAO) activity, dopamine beta hydroxylase (DBH) activity, and testosterone levels. Among males, high SSSV scores, high testosterone levels, and low MAO activity contributed to the variance in alcohol use, whereas among females, a significant proportion of the variability in alcohol use was accounted for by high SSSV scores, high DBH activity, and younger age. PMID- 7785485 TI - Exercise enhances the maintenance of smoking cessation in women. AB - We examined the effects of physical exercise on smoking relapse. Twenty previously sedentary female smokers were randomly assigned to smoking cessation plus exercise or smoking cessation with frequency contact control. The smoking cessation program included 12 professionally led sessions over 12 weeks. Exercise treatment included three supervised exercise sessions per week for 15 weeks. Contact control included three women's health/wellness lectures per week for 15 weeks. Smoking abstinence was validated by carbon monoxide and saliva cotinine. Mean exercise attendance for exercise subjects was 88% with an increase in estimated VO2 of 25%. The percentage of subjects who quit for 24 hours was 80% for the exercise and 90% for the contact group. One subject in the contact group remained abstinent at the end of the 12-week treatment and at 1-, 3-, and 12 month follow-ups, whereas three subjects in the exercise group were abstinent at these time points. These results suggest that exercise training improves short term quit rates and may prove a useful strategy for long-term maintenance of smoking cessation. PMID- 7785487 TI - The pathogenesis of rheumatoid arthritis and the development of therapeutic strategies for the clinical investigation of biologics. AB - This review discusses current concepts of the pathogenesis of rheumatoid arthritis. It is proposed that RA is a T cell mediated disease following which a large number of subsequent inflammatory events are unleashed. Many of the pathogenetic steps are targets for new therapies including biologics. Laboratory, clinical and radiological methods of assessing disease activity are sufficiently sensitive and reproducible to permit their use in multicentre studies capable of detecting a biologic with disease modifying activity. The clinical assessment of the efficacy and toxicity of biologics poses unique problems. These have been illustrated by the example of 3 monoclonal antibodies directed against ICAM-1, CD4 and TNF alpha. The main role of most biologics may be to pinpoint important therapeutic targets which can be attacked by more easily administered and less costly xenobiotic drugs. PMID- 7785488 TI - Inflammation, Mechanisms and Therapeutics. Proceedings of the 7th International Conference of the Inflammation Research Association. White Haven, Pennsylvania, September 25-29, 1994. PMID- 7785489 TI - Regulation of alpha 6 beta 1 integrin-mediated migration in macrophages. AB - Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. P388D1 macrophages that had been transfected with the alpha A integrin subunit were 3-4 fold more migratory than P388D1 macrophages that had been transfected with the alpha 6 B integrin subunit. Deletion of the alpha 6 cytoplasmic domain markedly inhibited the ability of the alpha 6 beta 1 receptor to promote migration. PMID- 7785491 TI - C. Gordon van Arman Scholarship Competition 7th International Conference of the Inflammation Research Association. PMID- 7785492 TI - New animal models of inflammatory disease workshop. PMID- 7785493 TI - Cell adhesion workshop. PMID- 7785490 TI - Site-directed mutagenesis--molecular biology and rational drug design. AB - Using site-directed mutagenesis, we have determined the location and composition of the binding sites in human IL-1 alpha and IL-1 beta for the Type I IL-1 receptor (IL-1R). The binding site in each ligand is a discontinuous epitope made up of at least seven amino acids whose side chains are exposed on a contiguous region of the protein surface. Although human IL-1 alpha and IL-1 beta have similar affinities and cross-compete for binding to the human Type I IL-1R, the binding site residues are not identical in the two ligands. In addition, the residues in the binding site of each ligand contribute differently to binding of the human versus the mouse IL-1R. The structure of the IL-1 binding site has implications for the rational design of IL-1 antagonists. PMID- 7785494 TI - Cartilage degradation and osteoarthritis workshop. PMID- 7785495 TI - New drugs in phase I and beyond workshop. PMID- 7785498 TI - Inflammatory cytokines workshop. PMID- 7785497 TI - Lipid mediators: mechanisms. PMID- 7785499 TI - Pulmonary inflammation workshop. PMID- 7785496 TI - Lymphocyte activation and immunoregulation workshop. PMID- 7785500 TI - Poster discussion lipid mediators--new agents. PMID- 7785502 TI - Cytokine networks in rheumatoid arthritis: implications for therapy. PMID- 7785503 TI - T cell receptor peptide vaccines as immunotherapy. PMID- 7785501 TI - Immunoglobulin gene expression in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is characterized by inflammation of synovium, in which immunoglobulin-secreting plasma cells are generally present. The forces driving immunoglobulin expression in RA synovium are unknown. Sequences of VH and VK transcripts from an RA synovial cDNA library demonstrate patterns of somatic mutation typical of an antigen-driven response. Moreover, 5% of the kappa repertoire appears to derive from the same B cell progenitor, suggesting an oligoclonal response. Immunoglobulin expression in this synovium thus appears to result from antigen stimulation. In addition, this patient's synovium is enriched for unusually long VK-JK joins (CDR3s), suggesting abnormal selection or regulation of the B cell response in RA. PMID- 7785504 TI - Antigen specific therapies for the treatment of autoimmune diseases. PMID- 7785505 TI - Protein kinase C in cell signaling: strategies for the development of selective inhibitors. AB - Protein kinase C plays a central role in the cellular signaling pathway for the lipophilic second messenger sn-1,2-diacylglycerol, which is involved in many biological responses, including tumor promotion and inflammation. A major effort has been directed at understanding diversity within this system in order to develop strategies for selective inhibition. Two classes of ligands for the regulatory domain of protein kinase C have been identified which, although they function in vitro as activators of the enzyme, paradoxically behave in vivo as partial antagonists. Identification of targets for the phorbol esters distinct from protein kinase C argues that antagonists acting on the regulatory and catalytic domains of protein kinase C will have different spectra of action. PMID- 7785508 TI - [Distribution of free amino acids and related compounds in ocular fluids of rat- I. Aging and inherited cataracts]. AB - The distribution of free amino acids and their related compounds has been determined in the aqueous humors of Wistar strain and Ihara cataract f-strain (ICR) aging rats. Taurine was the most abundant amino acid in aqueous humors except in ICR rats of 16 and 70 weeks. It was supposed that the increase of serine and glutamine, and the decrease of aspartate, proline and glycine in aqueous humors were related to aging. There were interesting changes in amino acids related to opacity of lens, concentration of taurine was lower than that of Wistar rats in ICR rats of 4, 16, and 70 weeks, alanine and citrulline increased in Wistar rats and decreased in ICR rats, and histidine increased in ICR rats with aging. The changes in free amino acids in aqueous humors were the greatest in ICR rats, and these data will provide useful clues for the formation of cataract and the transportation of amino acids. PMID- 7785506 TI - [Recent advances in neuro-ophthalmological research and clinical application]. PMID- 7785507 TI - [Induction of oral tolerance to experimental allergic conjunctivitis in rats]. AB - Immunological tolerance can be induced by the oral administration of antigen. We induced oral tolerance rats to experimental allergic conjunctivitis by ovalbumin and investigated the suppression of inflammation. In groups which had started eating antigen both before and after the immunization, the serum anti-ovalbumin IgE level measured by passive cutaneous anaphylaxis reaction was significantly lower than in a group that had not been fed antigen. The intensity of experimental allergic conjunctivitis in the group which had started eating antigen before immunization, was significantly suppressed in regard to the leakage of Evans Blue from conjunctival vessels 30 minutes after the challenge and the neutrophil infiltration 6 hours after. The dye leakage of the group which had started feeding after immunization was also significantly suppressed. There was a positive correlation between the serum IgE level and the leakage of Evans Blue (r = 0.90, p < 0.001). These results suggest that the suppression of antigen specific IgE antibody production caused by oral tolerance affected the decrease of local inflammation on the conjunctiva. PMID- 7785510 TI - [In vitro topically applied fluoroquinolone penetration into the anterior chamber]. AB - The penetration mode of five fluoroquinolone ophthalmic solutions (OFLX, NFLX, LVFX, LFLX and CPFX) through the rabbit cornea was examined with an in vitro experimental system. The system was an artificial anterior eye segment model made of acrylamide covered with a New Zealand albino rabbit cornea with a scleral flap. In vivo studies on the penetration of OFLX and NFLX ophthalmic solutions into the anterior chamber of albino rabbits were performed separately. Parameters gained from in vivo pharmacokinetic analysis and those from the model eye were compared. The permeability coefficients (K) (cm/s) through the cornea and partition coefficient were 6.95 x 10(-7) cm/s in LVFX, 6.78 x 10(-7) cm/s in OFLX, 3.58 x 10(-7) cm/s in LFLX, 2.46 x 10(-7) cm/s in CPFX and 0.06 x 10(-7) cm/s in NFLX, and 0.24, 0.23, 0.14, 0.06 and 0.07, respectively. High correlation was seen between the corneal permeability coefficients, and the partition coefficient Cmax of OFLX obtained from the in vivo study was higher than that of NFLX. The applied experimental system would be a useful tool for the estimation of the in vivo Cmax of the examined drug. PMID- 7785509 TI - [Permeability to horseradish peroxidase of the ciliary muscle vessels of squirrel monkeys]. AB - The morphology and permeability to horseradish peroxidase (HRP) of the ciliary muscle capillaries of squirrel monkeys were studied. The endothelial cells of the capillaries were of the continuous type and the interendothelial clefts were closed by a zonula occludens. Many vesicles were present in the cytoplasm of the endothelial cells. In addition to these vesicles, large vacuole-like structures, 100-500 nm in diameter, were observed in the cytoplasm of capillary endothelium, especially in the circular and radial ciliary muscles. When HRP was perfused into the anterior chamber, the 3,3'-diaminobenzidine reaction product was observed in the lumen of the ciliary muscle vessels after 30 minutes. When HRP was administered intravenously, the reaction product was observed among the muscle fiber bundles after 15 minutes. In both cases, the reaction products were also present in the cytoplasmic vesicles and vacuole-like structures, suggesting that these structures are involved in the bidirectional transport of HRP between interstitium and blood. PMID- 7785511 TI - [MHC and non-MHC gene effects on the development of experimental autoimmune uveoretinitis]. AB - Experimental autoimmune uveoretinitis (EAU) can be induced in rats by interphotoreceptor retinoid-binding protein (IRBP), and served as a model for human uveitis. Using IRBP-derived peptide R16, we investigated the MHC and non MHC genes' effect on the regulation and susceptibility to EAU. EAU-high susceptible LEW (RT1l), EAU-low susceptible WKAH (RT1k), and WKAH.1L rats which carry RT1l and WKAH background were immunized with 2 nmol of R16. One hundred percent of LEW rats developed EAU and 92.9% of WKAH. 1L rats. Only, 18.8% of WKAH rats developed EAU. Among these strains tested, the severity of EAU was 2.06 in LEW, 1.23 in WKAH.1L, and 0.38 in WKAH. R16 evoked substantial proliferative responses in all these strains. The present data suggest that both MHC and non MHC genes play distinct roles in development of EAU. PMID- 7785512 TI - [Endothelin receptors in bovine retinal vessels--quantitative receptor autographic analysis with radioluminography]. AB - Endothelin (ET) receptors in bovine retinal macrovessels, microvessels, and nonvascular tissues were characterized using a quantitative receptor autoradiographic method with 125I-endothelin-1 (125I-ET-1), ET-1, ET-, ET-3, BQ123 (a selective antagonist for the ETA receptor) and sarafotoxin S6c (an agonist for the ETB receptor). A quantitation was made with a computerized radioluminographic system and imaging plates. The method we used revealed that there were specific binding sites for 125I-ET-1 in the bovine retinal macrovessels, microvessels, and nonvascular tissues. There was no difference in the dissociation constant (Kd) showing binding characteristics between the retinal macrovessels and the microvessels. The bindings to the retinal macrovessels and the microvessels were effectively displaced by BQ123, whereas the binding to the retinal nonvascular tissues was displaced by sarafotoxin S6c. Thus, we obtained evidence that macrovessels and microvessels of the bovine retina have ETA receptor, and that the nonvascular tissues have ETB receptors. PMID- 7785513 TI - [An electrophysiological study on the effect of antioxidant drugs against retinal ischemia-reperfusion damage]. AB - The effects of antioxidant drugs on retinal ischemia-reperfusion damage were studied by electroretinograms (ERGs) from reperfused Dutch rabbit eyes. After inducing retinal ischemia by increasing the intraocular pressure (IOP) up to 140 mmHg for 60 minutes, the reperfusion was started by lowering the IOP to the normal level. Mannitol, polyethylene glycol superoxide dismutase (PEG-SOD), or ascorbic acid was administered by drip-infusion to the rabbits immediately after (early group) or 1 hr after (delayed group) the start of reperfusion. Saline, as a control, was administered by the same method as the early group. The a- and b waves were recorded before the ischemia and during the reperfusion. In the early group treated by each drug, the recovery rates of the b-wave amplitudes at 4 hrs after the start of reperfusion were significantly greater than those in the controls. In the delayed group, the ERG recovery rate in rabbits treated with PEG SOD was significantly better than in the controls. These results indicated that all these drugs were effective in protecting from the retina from the ischemia reperfusion damage, and that some antioxidant drugs might be effective even when they were administered after the start of reperfusion. PMID- 7785514 TI - [Matrix metalloproteinase in the cynomolugus monkey optic nerve heads]. AB - Gelationolytic and caseinolytic activity of matrix metalloproteinase in normal cynomolugus monkey optic nerve heads was investigated. Optic nerve heads of three eyes were incubated in the media for 20 hours. Each media was applied to the gelatin or casein containing gels, and zymography was performed. Major bands of 94 kDa and 62 kDa gelatinase activities were demonstrated in all three eyes. In one eye gelatinolytic activity of the 58 kDa band was also demonstrated. Caseinase activity was not detected in any of the three optic nerve heads. PMID- 7785515 TI - [Localization and response characteristics of thalamic corneal units in the cat]. AB - Units in the thalamus responsive to mechanical stimulation of the cornea (thalamic corneal units) were studied in urethane-chloralose anesthetized cats. Four different classes of corneal units were found in the nucleus ventralis posteromedialis (VPM) and intralaminar nuclei. They corresponded to 4 different classes of corneal units in the trigeminal subnucleus caudalis and adjacent bulbar lateral reticular formation reported by Nishida (1987). Low threshold corneal specific (LTCS) units, whose mechanical threshold was well below the pain threshold in patients with cataract, were located in the dorsolateral part of the VPM proper. High threshold corneal specific (HTCS) units and wide dynamic range (WDR) units, whose mechanical threshold was well above the pain threshold of the human cornea, were located in the shell region of caudal VPM. Each class of these three corneal units was incorporated in the somatotopic organization of low threshold mechanoreceptive, nociceptive specific, or WDR units having a cutaneous receptive field in the contralateral trigeminal nerve territory. Units having receptive fields in the head similar to those of subnucleus reticularis ventralis (SRV) units were found in the intralaminar nuclei. Their corneal mechanical thresholds were much the same as those of HTCS units and WDR units. These results supported the suggestion that both nonpainful sensation and pain can be evoked in the cornea. PMID- 7785516 TI - [A new method to elicit pathological entoptic phenomenon from the retina- stenopeic flicker test]. AB - Patients with central serous chorioretinopathy noticed that a part of the visual field became light for a few seconds when half of the visual field was covered in front of the eye. We devised a stenopeic flicker test (s-f test) to elicit this phenomenon continuously, and evaluated the clinical usefulness. We examined 17 eyes with central serous chorioretinopathy using the s-f test and Amsler grid test. Retinal abnormality was detected in 17 of 17 eyes with the s-f test and 14 of 17 eyes with the Amsler grid test. In detecting the extent of the retinal detachment on fluorescein angiograms, the s-f test (p < 0.0001, r = 0.842) was more precise than the Amsler grid test (p < 0.0003, r = 0.506). These results suggest that the s-f test is useful to detect retinal abnormality and to grasp the extest of the retinal detachment in central serous chorioretinopathy. PMID- 7785517 TI - [An apparatus using laser speckle phenomenon for noncontact two-dimensional analysis of microcirculation in optic nerve head or choroid in human eyes]. AB - The previously reported apparatus using the laser speckle phenomenon for noncontact two-dimensional analysis of the fundus peripheral circulation was improved so that peripheral circulation in the optic nerve head (ONH) or choroid in human eyes can be measured on a real-time basis. The fundus was illuminated by a diode laser spot and its image speckle was detected with an area sensor. The NB value, a quantitative index of blood velocity, was calculated by the logic board every 0.125 sec successively for 7 sec. Using this apparatus, the NB averaged over the measurement field located in the temporal site of ONH, free of visible surface vessels (NBONH), and that located in the posterior choroid (NBCh) were measured in normal human eyes. The coefficients of reproducibility of 5-minute interval measurements were 11.7% for the NBONH averaged over 5 pulses (mean NBONH) and 8.7% for the NBONH averaged over 5 pulses (mean NBCh), and those of 24 hour interval measurements were 13.0% for the former and 9.7% for the latter, respectively. The average of pulsatile component of NBONH was 38.4% of mean NBONH and that of NBCh was 26.6% of mean NBCh. PMID- 7785518 TI - [Static characteristics of accommodation on the relationship between accommodative resting position and viewing distance]. AB - The steady-state accommodation of subjects during a 15 min visual task was measured in real time by an infrared optometer to investigate the relationship between accommodative resting position and the effect of viewing distance. When the subjects were loaded at 50 cm (closer than their resting state), the steady state accommodation showed an inward shift which was enhanced when computation was done. On the contrary, when they worked outside their resting position-2m viewing distance-, an outward shift of steady-state accommodation was seen in the control group who reacted only to the visual objects displayed. For the mental task group this was not evident. It appears that the steady-state accommodation is different between the cases of visual stimuli given inside and outside the resting position. PMID- 7785519 TI - [Functional magnetic resonance imaging of the human primary visual cortex during visual stimulation]. AB - Signal changes in the human primary visual cortex during visual stimulation were evaluated using non-invasive functional magnetic resonance imaging (fMRI). The experiments were performed on 10 normal human volunteers and 2 patients with homonymous hemianopsia, including one who was recovering from the exacerbation of multiple sclerosis. The visual stimuli were provided by a pattern generator using the checkerboard pattern for determining the visual evoked potential of full field and hemifield stimulation. In normal volunteers, a signal increase was observed on the bilateral primary visual cortex during the full-field stimulation and on the contra-lateral cortex during hemifield stimulation. In the patient with homonymous hemianopsia after cerebral infarction, the signal change was clearly decreased on the affected side. In the other patient, the one recovering from multiple sclerosis with an almost normal visual field, the fMRI was within normal limits. These results suggest that it is possible to visualize the activation of the visual cortex during visual stimulation, and that there is a possibility of using this test as an objective method of visual field examination. PMID- 7785520 TI - [A case of multifocal choroiditis associated with progressive subretinal fibrosis]. AB - Multifocal choroiditis associated with progressive subretinal fibrosis, which was reported by Cantrill and Folk in 1986, is characterized by acute multifocal choroiditis resulting in progressive subretinal fibrosis. All cases were young, healthy females. Our case was a 17-year-old female who complained of visual disturbance in her left eye. Ophalmoscopy showed multiple, small, yellowish-white hypopigmented, choroidial lesions in the posterior fundus of her left eye. These lesions showed hyperfluorescence in fluorescein angiography and hypofluorescence in indocyanine green (ICG) angiography. One month later the yellowish-white hypopigmented, choroidal lesions increased in number and subretinal fibrosis appeared in the macular area. Two months later subretinal fibrosis was also found in the area except for the macula. In her right eye, ophthalmoscopy and fluorescein angiography showed no abnormal findings, but ICG angiography revealed choroidal hypofluorescence areas. Two years later the subretinal fibrosis was increased and the yellowish-white lesions showed pigmentation. PMID- 7785521 TI - [Horizontal gaze palsy due to lesion of the abducens nucleus detected with magnetic resonance imaging]. AB - A case of unilateral horizontal gaze palsy is reported. The lesion of the abducens nucleus was clearly detected with magnetic resonance imaging. In the early stage, the adduction of the right eye and abduction of the left eye were completely limited and the vestibulo-ocular reflex was also impaired. However, during the recovery stage, the improvement of limitation of abduction was delayed compared with that of adduction. We suggest that this phenomenon is useful as a differential diagnosis between lesions of the abducens nucleus and of the paramedian pontine reticular formation. PMID- 7785522 TI - Mapping the densities of malaria vectors within a single village. AB - Small scale spatial variation and temporal heterogeneity in mosquito densities can have important consequences for disease transmission, but the extreme variation which is observed in populations of malaria vectors makes it difficult to obtain good predictions of densities for short time periods over limited areas. We have applied Bayesian techniques derived for use in cancer epidemiology in order to map densities of Anopheles gambiae s.l. and A. funestus in a Tanzanian village where there is intense transmission of Plasmodium falciparum malaria. Estimates derived in this way should prove useful in vector population biology and in improving estimates of exposure-response relationships of the human host to malaria. The same methods can be applied in other fields of animal ecology. PMID- 7785523 TI - Immunodiagnosis of schistosomiasis mansoni in a low endemic area in Surinam by determination of the circulating antigens CAA and CCA. AB - We evaluated the applicability of circulating antigen detection in serum and urine for the diagnosis of Schistosoma infections in a low endemic area. In total 389 individuals from Saramacca (Surinam) participated in the survey. Stool samples were examined using the Kato method, while circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were determined by highly specific monoclonal antibody-based ELISA's. Also schistosome specific IgM antibodies were measured by the indirect immunofluorescence assay, but the diagnostic performance of this test was found to be poor in this population. S. mansoni eggs were found in 29% of the examined cases, while CAA and CCA could be demonstrated in 23% and 17% of the serum samples and in 3% and 28% of the urine samples, respectively. Forty three percent of the study population was positive in at least one of these diagnostic assays, indicating that each individual test misses a substantial part of the subjects with an active infection. In most positive cases, intensities of infection were very low. As 204 individuals participated in all screening assays, diagnostic performance of each test was evaluated in this sub-population. The highest sensitivities were achieved with the urine-CCA assay and the parasitological examination, detecting 59 and 58 out of the 107 cases with an active infection, respectively. The serum-CAA assay detected 47 positive cases. Our results demonstrate that determination of circulating antigens, especially CCA in urine and CAA in serum, provides information additional to the parasitological examination, for the assessment of prevalence and intensity of Schistosoma infection in low endemic areas. PMID- 7785524 TI - Characterisation of taeniid cestode species by PCR-RFLP of ITS2 ribosomal DNA. AB - Seven species of taeniid cestode (Echinococcus granulosus. E. multilocularis, Taenia hydatigena, T. ovis, T. pisiformis, T. multiceps and T. serialis) were characterised using a polymerase chain reaction-based restriction fragment length polymorphism technique (PCR-RFLP). The second internal transcribed spacer of ribosomal DNA (ITS2) was amplified from various geographical isolates of each of the seven species, digested separately with four restriction endonucleases and the fragments were separated by conventional agarose gel electrophoresis. PCR RFLP produced characteristic patterns for each taeniid species examined. No variation in RFLP patterns was observed among different isolates of E. multilocularis and the species of Taenia, but distinct intraspecific variation was detected in E. granulosus. The present study indicates the usefulness of the PCR-RFLP of ITS2 for systematic, epidemiological and diagnostic purposes. PMID- 7785526 TI - Anaemia and Plasmodium falciparum infections among young children in an holoendemic area, Bagamoyo, Tanzania. AB - Although the aetiology of anaemia in tropical areas is multifactorial, Plasmodium falciparum malaria is commonly associated with anaemia in children living in holoendemic malaria areas. Such an association was examined in a population based study of 338 children 6 to 40 months of age living in the Bagamoyo area of Tanzania. Stepwise regression analysis showed that fever and parasitaemia were effective in predicting anaemia and that the anaemic condition was age dependent. The majority of the children were iron deficient, followed by normochromic macrocytic anaemias. There was strong evidence in this age group that the anaemia was associated with malaria and not geohelminth infection. The importance of malaria and anaemia as a cause of childhood morbidity in Africa is discussed. This condition has taken on new significance with the realization that blood transfusions commonly used to treat severe anaemia are a major vehicle for Human Immunodeficiency Virus (HIV) transmission. PMID- 7785525 TI - Social aspects of malaria in Heping, Hainan. AB - This paper presents findings from a study conducted in Heping Town, Qiongzhong County, Hainan Province, China. The study, conducted in 1992, used qualitative as well as quantitative methods to gather social, cultural and behavioural data associated with the acquisition, transmission and prevention of malaria, and the diagnosis and treatment of disease. These methods included focus groups, key informant and other in-depth interviews, and observations, a household survey and tests of school children of knowledge of malaria. The study is among the first to our knowledge that has utilized this broad mix of methods for tropical disease research in China. PMID- 7785528 TI - Establishment of a partly DFMO-sensitive primate model of Trypanosoma rhodesiense sleeping sickness. PMID- 7785527 TI - Inoculum size and severity of malaria induced with Plasmodium ovale. AB - Although it might be expected that the size of the infecting inoculum would influence the severity of the consequent malaria, evidence that it does so is scarce. Using records from 80 non-immune neurosyphilis patients who received malaria therapy with a single strain of Plasmodium ovale by blood inoculation, the relationships between the number of trophozoites inoculated, the prepatent period, and measures of severity of the resulting malaria were examined. The number of trophozoites was not related to any of the outcome measures, but patients with shorter prepatent periods had higher and more peaks of fever and longer lasting infections. PMID- 7785529 TI - Proceedings of the Belgian Society of Urology International Congress. Ghent, May 12-13, 1995. PMID- 7785530 TI - Clinical history and computerized questionnaires in the evaluation of incontinence. PMID- 7785531 TI - Commercial television bladder dysfunction. AB - Bladderdysfunction seems to have an increasing frequency in infancy, and especially in children without obvious congenital organic or functional bladderdysfunction. The disorder seems is related with changes in our behaviour, that are stimulated by familial and social pseudo-reasons. Commercial interests and marketing play a major role. This leads to wrong dry-training, an exaggerated hygienic education, prudisheness, wrong toilet-posture, lack of time to void, post-poning, wrong drink- and void-pattern, wrong food-pattern and increasing constipation. Prevention is necessary by an adapted reeducation of parents ans society. PMID- 7785532 TI - Female incontinence: critical analysis of diagnostic procedures. PMID- 7785533 TI - Reducing uncertainty for vesico-urethral sonography in women. AB - The author endeavours to detail the technical modalities which can be used to avoid uncertainty in urodynamic sonography, and to obtain easily reproducible quality imaging. The 5 major techniques (transparietal, transperineal, introital, endovaginal and endorectal) are compared. The artifacts generated are described. A choice between these different techniques is performed as a function of the methodological advantages specific to each of them and the clinical applications contemplated by the sonographer. The characteristics of the "ideal" equipment are defined to help the sonographer-to-be to choose his or her equipment with full awareness of the facts (characteristics of the probe, emission frequency, settings by the sonographer, automatic image freeze during coughing). The methodology is described in detail and widely illustrated: position of the patient, choice of the section plane, choice of the reference system, location of the urethra, and definition of the vesical neck, maintenance of the probe position during effort or free movement, degree of vesical fullness, choice of the parameters. Some difficulties can be linked to the patient's anatomical characteristics (vaginal scar, short or narrow vagina, twisted urethra,...); ways to avoid them are briefly described. PMID- 7785534 TI - Female urinary incontinence: imaging by or for the urologist. AB - The author reviews the imaging techniques useful in the evaluation of female urinary incontinence: voiding cystourethrography and videoradiourodynamics. Voiding cystourethrography allows to disclose two forms of bladder base suspension defects: anterior and posterior suspension defects. It will be performed before surgery. Videoradiourodynamics will be limited to patients with recurrent urinary incontinence following unsuccessful surgery. PMID- 7785535 TI - Female incontinence: critical analysis of diagnostic procedures. AB - Urodynamic procedures when required as part of the evaluation of female urinary incontinence should be tailored to the individual case. A wide range of tests are available which are reviewed with hints to which will add most information to previously obtained clinical data. PMID- 7785536 TI - Minimal prerequisites to operate a stress-incontinent woman. PMID- 7785537 TI - Non surgical treatment of female incontinence. PMID- 7785538 TI - Indications and operative treatment of stress urinary incontinence. PMID- 7785539 TI - The artificial urinary sphincter AMS 800: our experience in women with or without uterine prolapse. PMID- 7785540 TI - Colpopromontoriopexy. AB - This is a review article about the colposacropexy and the colpopromontoriopexy in the treatment of vaginal prolapse. We reviewed the literature through the eyes of a urologist dealing with genuine stress incontinence. The treatment of genuine stress incontinence without sphincterdeficiency consists in the correction of the anterior compartment prolapse. Preoperative it is important to examen the middle and the posterior compartment of the vagina in order to achieve good postoperative results. Most urologists cure genuine stress incontinence with an abdominal approach. The combination of a colposuspension and a colpopromontoriopexy is an operation that corrects anterior, middle and posterior compartment prolapse by the same approach without significant more complications or bloodloss. PMID- 7785541 TI - Testicular and vascular changes in patients with varicocele. PMID- 7785542 TI - Recurrence of varicocele after spermatic vein embolization in young patients: radiological aspect. PMID- 7785543 TI - [Antegrade scrotal sclerotherapy in the treatment of varicocele]. AB - The antegrade scrotal sclerotherapy is a minimally invasive surgical technique in the treatment of the varicocele. Through a small scrotal incision a straight vein merging in the spermatic vein is isolated and cannulated. An antegrade phlebography is performed and ethoxysclerol is injected in the vein. We have performed this technique in 35 patients with a follow-up of at least 3 months. All patients except one (97%) show no more varicocele. This technique has a low morbidity, is cheap and as effective as the other treatment modalities. The antegrade sclerotherapy is competitive to the retrograde embolisation and has the advantage that the treatment can be performed in all cases, even in cases of recidive. PMID- 7785544 TI - [Laparoscopic treatment of recurrence and embolization failure of varicocele]. AB - Varicocele is a benign pathology, for which the less invasive treatment is percutaneous embolisation. Literature reports results from 70 to 85% (1,2). Laparoscopic treatment seems to be a good alternative for patients suffering from a recurrence, or patients who can not be embolised. We report our experience concerning the first 13 patients treated with laparoscopic technic. In all 13 cases it was possible to practice the technic, and patients were cured. PMID- 7785545 TI - [Examination of the non-palpable cryptorchid testis]. AB - Cryptorchidism affects approximately 1 in 150 boys. Non-palpable testes represent nearly 20% of all cases. If present, they are situated between the inferior renal pole and the external inguinal ring. Often at surgical exploration, however, a "nubbin" of testicular tissue is found at the end of blind ending spermatic vessels without demonstration of a recognizable testis; this finding is referred to as an absent testis. In other patients, no vascular or ductular (epididymis vas deferens) or even testicular structure can be observed. This situation defines true testicular agenesis. Non-palpable testes have an increased risk of malignant transformation, infertility, associated inguinal hernia and congenital ductular abnormalities. Surgical treatment is often more complex and unsuccessful. Many imaging diagnostic methods to investigate patients with non palpable testes (pneumoperitoneography, angiography, ultrasonography, CT scan and RMN) have been used so far but none of these has been uniformly accepted as the ideal investigative technique because they are unreliable and/or they involve a fair risk. Since Cortesi and associates first described in 1976 a case of abdominal testes identified by laparoscopy, this technique has gained increased acceptance by pediatric urologists and surgeons. Today, celioscopy plays a central role in the exploration of non-palpable cryptorchid testes. The authors try to establish an algorithm methodology for investigating non-palpable testes under the light of recently reported anatomical, pathological and surgical data. PMID- 7785546 TI - Hormonal treatment of cryptorchidism: lessons from 15 years of worldwide experience. PMID- 7785547 TI - Cryptorchidism: the disease and its management. PMID- 7785548 TI - Laparoscopy: any indication in the work-up and treatment of undescended testis? AB - About 10% of undescended testis are non palpable. Surgical exploration of the inguinal region was the standard treatment, mainly because reliable "localisation tests" were not available. Today, laparoscopy is becoming the first step for optimal management of this problem. This technique combines relevant diagnostic information with therapeutic facilitations. PMID- 7785549 TI - Female incontinence. Clinical examination by the gynecologist. PMID- 7785551 TI - Pitfalls in urodynamic investigations in children. AB - For the evaluation of bladder (dys)function in young children with neuropathic bladder or other congenital malformations urodynamic investigations have become widely accepted. Although urodynamic studies can be conducted as early as the newborn period, there are some specific studies that can only be performed in somewhat older children, such as pressure-flow studies. Unlike adult patients, children most often do not understand why such an invasive study needs to be performed and are therefore less co-operative. In order to make the study as pleasant as possible some special measures have to be taken. This paper describes the different modalities available to perform urodynamic investigations in children, its drawbacks, pitfalls, indications, clinical implications and prerequisites. PMID- 7785550 TI - Bladder function and non-neurogenic dysfunction in children: classification and terminology. AB - Urological function and dysfunction in children are different from function and dysfunction in adults. The dynamics of the urinary tract in children are more complex as development from simple reflex controlled infant bladder to mature bladder function takes place during the first five years of live. The most crucial event in this development is the maturation of the inhibition that takes place in the growing urinary tract. Apart from gaining neurological control over de lower urinary tract there is the physical growth of the bladder-sfincter unit. Otherwise in children there exist a large amount of structural organic congenital pathology of the lower urinary tract that can trouble the normal development. Finally there is the cognitive function that has no anatomical substrate in the lower urinary tract but which takes place in the central nervous system and which is influenced by training and which can play a major role in development of non structural functional dysfunction. In order to train a child adequately the anatomical structure needs to have undergone enough maturation. By training a child on a too early age one can help to develop non structural functional dysfunction. In a time where competition in dry-training is encouraged by commercial pressure and where parents have less time, so that they are urged to train their children dry, more and more non-structural functional dysfunction in children is seen. The most prominent symptom of maldevelopment of the urinary tract, be it structural or functional is urinary incontinence. It is the most common problem seen in the paediatric urology practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785552 TI - [Evaluation of surgical treatment for bone metastatic lesion in renal cell carcinoma]. AB - Ten renal cell carcinoma (RCC) patients with bone metastatic lesions were treated in the Kyoto Prefectural University of Medicine between January, 1977, and December, 1992. Surgical treatment for the metastatic lesion was performed on 4 patients, while conservative treatment was performed on the other 6 patients. Surgical treatment made the patients painless consecutively, resulting in higher activities of daily life. However, recurrence of RCC developed in all the cases between 2 and 7 years later. Surgical treatment for the metastatic lesion was considered to be only a palliative therapy for RCC with bone metastasis and the indication should be limited to patients expected to have a good prognosis. PMID- 7785553 TI - [Clinical study on antimicrobial prophylaxis following extracorporeal shock wave lithotripsy]. AB - One hundred and sixty one patients with upper urinary stones were examined for antimicrobial prophylaxis following extracorporeal shock wave lithotripsy (ESWL). They were divided into two groups, the low-risk group (n = 133) and high-risk group (n = 28), according to the risk factors of urinary tract infection. The patients in the low-risk group were further randomized into two groups which were orally given ofloxacin for 7 days after ESWL (Group A, n = 66), no antimicrobial (Group B, n = 67). The patients in the high-risk group were randomly subdivided into three groups which were given flomoxef intravenously for 2 or 3 days and ofloxacin for 4 or 5 days thereafter (Group C, n = 10), flomoxef only for 2 or 3 days and no drugs later (Group D, n = 10), ofloxacin for 7 days (Group E, n = 8). In all of the patients in the low-risk group, during the 7 days after ESWL, fever elevation was observed in only 1.5% of patients, and bacteriuria in 10.0% on the 7th day. There was no difference in frequency of fever elevation and bacteriuria following ESWL between Group A and Group B. These findings indicate that prophylactic antimicrobial after ESWL treatment is not necessary for low risk patients with urinary tract infections. In the high-risk group, the over-all rates of fever elevation and bacteriuria were 21.4% and 24.0% respectively. The difference of effectiveness among the prophylactic regimens of the three groups (Group C, D, E) was not shown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785554 TI - [Expression of PCNA/cyclin, p53, C-erbB-2 versus histological grade in transitional cell carcinoma of urinary bladder]. AB - It is important to know the proliferating ability and the malignant potential of tumor tissues. We have examined the expression of PCNA/cyclin, p53 and C-erbB-2 in transitional cell carcinoma of the human urinary bladder by an immunohistochemical method, and compared the results with the histological grade, stage and survival rate. Immunohistochemical studies, using monoclonal and polyclonal antibodies, on these proteins were performed with formaline fixed paraffin sections of tumor tissue from 40 patients with bladder cancer. Generally, a higher grade and higher stage tumors expressed PCNA/cyclin, p53 and C-erbB-2 with a greater frequency than the tumors with a lower grade and lower stage and strongly stained cases had a lower survival rate than weakly stained cases. These findings suggest that the detection of each antigen is useful for estimating the malignant potential of transitional cell carcinoma as the adjuvant studies, because of its applicability to paraffin-embedded tissue sections and its simple, rapid technique. PMID- 7785555 TI - [Morphological changes in major pelvic ganglion neurons and histological structure of bladder using rat model of partial urethral ligation]. AB - Ninety six rats were divided into 4 groups (normal control group (N = 4), ligation group (N = 20), ligation-removed group (N = 36), and sham surgery group (N = 36)). The neuronal size of the 4-week ligated rats returned to normal 6 weeks after removal of the ligation. Rats ligated for 7, 11 and 20 weeks also exhibited a significant increase in the mean area but they could not make a complete recovery after removal of ligation for 6 weeks. Only the rats in the 1- and 4-week ligation groups could recover their neuronal size. Area densities of smooth muscle: connective tissue (ADsc ratio) was calculated using Elastica van Gieson staining sections of bladder strips. When ligation was removed, the ratio dropped and became nearly equal to the value of the sham surgery group. Only the 7-week group showed a lower ADsc ratio than the sham surgery group after the ligation was removed. These findings suggest that the reversibility of neuronal hypertrophy might become irreversible when the period of partial urethral ligation persisted beyond 7 weeks. Irreversible hypertrophy of major pelvic ganglion (MPG) neurons might be greatly related with the irreversibly enlarged fibrous bladder which could not show the same ADsc ratio as was seen in the sham surgery groups. PMID- 7785556 TI - [Experimental studies on evaluation of rat testicular function by 31P magnetic resonance spectroscopy]. AB - To evaluate the efficacy of 31P magnetic resonance spectroscopy (31P MRS) as a diagnostic method for abnormal testicular function, we examined three conditions using rat testes, ischemia, irradiation, and hormone manipulation. 1) Ischemia: Immediately after clamping of the feeding vessels, ATP signals began to fall and disappeared within 60 minutes. With the release of blood supply after 3 hours of ischemia, ATP appeared within 2 hours. However, after more than 4 hours of ischemia, ATP did not recover within 2 hours and the testis became necrotic after 1 week. 2) Irradiation: 31P MRS of the testis 2 weeks after irradiation with 10 Gy., 9 MeV showed a significant decrease (P < 0.05) in the PME/beta-ATP ratio from 1.30 +/- 0.11 (control level) to 1.11 +/- 0.12 and a decrease in PME/PDE ratio from 1.43 +/- 0.17 to 1.13 +/- 0.20. However 3 weeks later, the PME/beta ATP ratio recovered to a control level. 3) Hormone manipulation: In the testes 5 weeks after weekly intramuscular injections of estradiol benzoate and testosterone enanthate, PDE/beta-ATP ratio significantly increased (P < 0.01) from 0.83 +/- 0.09 (control level) to 1.03 +/- 0.19. 31P MRS is a non-invasive method for evaluation of various testicular abnormalities, and ATP signals may be useful to evaluate an acute ischemic change for example testicular torstion and the changes of PME, PDE signals may be useful parameters in the assessment of the status of spermatogenesis. PMID- 7785557 TI - [Consecutive annual changes in minimum inhibitory concentration in clinically isolated Neisseria gonorrhoeae strains]. AB - Between 1983 and 1991, 465 gonococcal strains isolated in the urological department of Japanese Red Cross Medical Center. The minimum inhibitory concentration (MIC) of these isolates to 22 kinds of antibiotics including penicillins (PC), cephems, tetracyclins (TC) and new quinolons (NQ) were determined and the annual difference of MIC was studied. The annual incidence of penicillinase producing neisseria gonorrhoeae (PPNG) of these 9 years were distributed in 3 to 17% and increasing tendency was not observed. As for Penicillin G, the MIC 90 of PPNG was seven fold higher than that of non-PPNG. No remarked difference was observed between MIC 90 of Cephems, TC and NQ of PPNG and non-PPNG. No annual difference was observed in MIC of PC, Cephems and SPCM. However the rising tendency of MIC was observed in NQ. PMID- 7785558 TI - Evaluation of effects of chitosan in preventing hemorrhagic cystitis in rats induced by cyclophosphamide. AB - Hemorrhagic cystitis is a common problem following cyclophosphamide or radiation therapy. Chitosan has been shown to be an effective hemostatic agent and promoter of wound healing in animal experiments. We evaluated the safety and efficacy of intravesical chitosan in an animal model of cyclophosphamide cystitis. Hemorrhagic cystitis was induced in female F344 rats by intraperitoneal cyclophosphamide, 100 mg/kg. Chitosan solution (0.3 ml) was instilled intravesically on day 1 (Group 1), on days 1, 3, and 5 (Group 2), or 1 hour after the administration of cyclophosphamide (Group 3). The rats in group 4 were treated with chitosan diluent on day 1 after cyclophosphamide, and the rats in group 5 received intravesical chitosan without cyclophosphamide. Sequential examination revealed decreased mortality and lower incidences of severe bladder bleeding, necrosis and inflammation in Group 3. Treatment delayed until after the appearance of the cystitis, especially repeated treatments, appeared to make the cyclophosphamide-induced changes worse. Used within 1 hour of cyclophosphamide administration, before the cystitis develops, chitosan seemed to have the possibility to inhibit the appearance of hemorrhagic cystitis. In addition to the changes in the bladder, severe changes occurred in the kidneys secondary to cyclophosphamide. PMID- 7785559 TI - [A case of middle ureteral tumor treated by end-to-end anastomosis following resection of 6.7 cm segment]. AB - A 71-year-old male with a right ureteral tumor in the midportion and contracted kidney of the opposite side, due to complete vesicoureteral reflux, underwent end to-end anastomosis after partial ureterectomy 6.7 cm in length. Our experience in this case led us to conclude that end-to-end anastomosis of the upper or mid portion of the ureter was possible for the maximal 7.0 cm length of the ureteral loss, when the kidney could be fixed downward as much as possible. PMID- 7785560 TI - [Intra-arterial chemotherapy with cisplatin, vincristine, methotrexate and adriamycin for recurrent penile cancer: a case report]. AB - A 60-year-old man visited our hospital with a chief complaint of penile tumor on November 13, 1984. Circumcision of true phimosis was performed and biopsy of the 27 x 27 mm fixed tumor on the glans revealed well differentiated squamous cell carcinoma. Seventy Gy of electron irradiation to the penis revealed a complete response. On February 1, 1985 bilateral inguinal lymph node dissection was performed and revealed metastasis to a left inguinal node. In May 1990, erosive changes occurred on the irradiated region, and local recurrence was confirmed. Since 2 courses of MBD (methotrexate, bleomycin, cisplatin) chemotherapy was not effective, additional wedge dissection was performed. In January 1992, local recurrence was found. Four courses of intra-arterial chemotherapy (cisplatin, vincristine, methotrexate, adriamycin) was performed with a complete response. No evidence of disease has been recognized for more than two years after completion of the treatment. PMID- 7785562 TI - [A case of granulomatous orchitis]. AB - A 69-year-old man complained of a painless left scrotal swelling. The scrotal mass was enlarged to a hen's egg size with a smooth surface. The scrotal ultrasonogram showed diffuse hypoechogenicity. A testicular tumor was suspected and left high orchiectomy was performed. Histopathological diagnosis was granulomatous orchitis. PMID- 7785561 TI - [Two cases of priapism cured by transcatheter embolization of internal pudendal arteries]. AB - We report here two cases of priapism. One of these cases was suspected to be drug induced and high and low flow mixed type. The patient had taken the drugs, alpha blocker for hypertension and dysuria by BPH for a long time. He was treated by a caveno-glandular shunt. After surgery, detumescence was obtained for some time, but erection appeared again soon. Transcatheter embolization of the internal pudendal arteries was then performed, and detumescence became permanent. The other case was an idiopathic and high flow type. Detumescence was achieved soon by transcatheter embolization of the internal pudendal arteries only, then he experienced morning erection imperfectly on the 9th day after this treatment. The management of priapism as reported to date is also reviewed. PMID- 7785563 TI - [Clinical statistics at the urological clinic of Sanjukai Hospital--statistics on new outpatients during the last five years]. AB - We report the clinical statistics of new outpatients for five years since 1989 at our hospital. The average total number of new outpatients in a year was 8309.8 (8122-8691) and new outpatients tended to show little change. The male to female ratio was 1.57:1, and 24.3% of the outpatients were referred to us by others sources. The representative operations on outpatients were circumcision, vasectomy, resection of condyloma and resection of caruncle. A statistical study was made on new outpatients according to the international classification of disease. There were 140.6 (1.97%) malignant urogenital tumors per year. Sexually transmitted diseases showed a tendency to increase for the last five years. In males the major disease was upper urinary tract stone (21-24%), prostatistis (21 24%) and benign prostatic hypertrophy (17-20%) and in females they were cystitis (58-61%), upper urinary tract stone (15-17%) and pyelonephritis (3-4%). We conclude that our hospital plays a major role as a private urological hospital. PMID- 7785564 TI - Duplex sonography after transjugular intrahepatic portosystemic shunts (TIPS): normal hemodynamic findings and efficacy in predicting shunt patency and stenosis. AB - OBJECTIVE: Portal hemodynamics are altered by placement of a transjugular intrahepatic portosystemic shunt (TIPS). Normal duplex sonographic findings after TIPS placement and hemodynamic alterations indicating shunt failure have not yet been well described. The purposes of this study were to determine normal hemodynamic changes on duplex sonography after TIPS placement and to assess the efficacy of duplex sonography in detecting shunt dysfunction. SUBJECTS AND METHODS: Forty patients underwent TIPS placement and were entered into a study that included routine sonographic evaluation and portal venography at regular intervals. Portal venography was also performed if shunt velocities on duplex sonography changed from the baseline, which raised the question of shunt stenosis or occlusion. The pre-TIPS duplex sonographic study included determination of patency, velocity, and flow direction in the main, right, and left portal veins and in the hepatic artery. Follow-up sonography included the pre-TIPS examination in addition to velocity determinations in three segments of the shunt. Correlation was made between 82 concurrent sonographic and portal venographic studies. RESULTS: High-velocity blood flow (mean peak velocity, 135-200 cm/sec) was consistently seen within patent, well-functioning shunts. Hepatic artery peak systolic velocities increased from 79 cm/sec before TIPS placement to 131 cm/sec after TIPS placement (p < .001). Main portal vein velocities increased from 21.8 cm/sec before TIPS placement to 41.5 cm/sec after TIPS placement (p < .001). When compared with portal venography, duplex sonography was 98% sensitive and 100% specific in predicting the presence of blood flow within the stent. Sonography was highly sensitive and specific for detecting stent stenosis. Final sonographic criteria for shunt stenosis in angiographically documented cases were low velocity shunt flow (< or = 60 cm/sec) in the entire stent, or low-velocity shunt flow with an associated focal velocity elevation. CONCLUSION: Consistent changes in portal venous and hepatic arterial hemodynamics are normally seen on duplex sonography after placement of a TIPS. Duplex sonography accurately predicts shunt patency and dysfunction when compared with portal venography. Duplex sonography is an effective, noninvasive method of evaluating shunt function and should be considered for use as the primary imaging technique in routine follow-up after TIPS placement. PMID- 7785565 TI - Pheochromocytoma of the bladder in an adolescent: sonographic and MR imaging findings. PMID- 7785566 TI - Filmless musculoskeletal radiology: why is it taking so long? AB - Digital images as an alternative to plain radiographs in musculoskeletal radiology have not been readily accepted to date. This article looks at the different aspects of filmless imaging and offers an opinion concerning this lack of acceptance. Although spatial resolution, image storage, and image transmission present potential problems, the greatest problem is image display. Commercially available workstations do not compete well with the speed and simplicity of the conventional film and view box. PMID- 7785567 TI - Predicting neurologic outcome with MR imaging in a patient in spinal shock. PMID- 7785568 TI - Increased signal in the normal supraspinatus tendon on MR imaging: diagnostic pitfall caused by the magic-angle effect. AB - OBJECTIVE: Increased signal intensity within the distal portion of the supraspinatus tendon during MR imaging is a frequent observation even in healthy subjects. This finding has been variously attributed to the presence of fat, muscle, connective tissue, abnormal vascularity, or degenerative changes. More recently, the effect of tendon orientation in the static magnetic field (Bo) has been implicated. It has been shown that tendons at the magic angle of 55 degrees to Bo show markedly increased signal. This study was designed to determine the contribution of the magic-angle effect to the MR signal in the distal portion of the supraspinatus tendon. SUBJECTS AND METHODS: Five healthy volunteers were imaged in a 1.5-T unit using short TR/TE sequences in standard supine position; they were then reimaged laterally flexed at the waist to reorient the plane of the distal portion of the supraspinatus tendon by approximately 20 degrees relative to Bo. In the second part of the study, three cadaveric shoulders were similarly imaged, first in standard position and then reoriented approximately 35 degrees by simple rotation of the specimen. The supraspinatus tendon was evaluated in each subject by noting the length of the segment with increased signal and the position of this segment relative to the insertion of the tendon on the greater tuberosity. Comparisons were made for each live and cadaveric subject between neutral and rotated positions. RESULTS: Segments of increased signal changed in length and position for each live and cadaveric subject from the neutral to the reoriented position. CONCLUSION: Our study suggests that tendon orientation contributes significantly to the presence of increased signal within the supraspinatus tendon, as caused by the magic-angle effect. Failure to recognize this effect may lead to diagnostic inaccuracy when evaluating the rotator cuff on short TR/TE sequences. PMID- 7785569 TI - Correlation of MR imaging and pathologic findings in athletes undergoing surgery for chronic patellar tendinitis. AB - OBJECTIVE: Jumper's knee, or chronic patellar tendinitis, can be a source of considerable pain in athletes. The changes that occur with shearing of the tendinous fibers from repeated microtrauma can progress to significant degeneration and increase the risk of tendon rupture. In order to better understand this phenomenon, a correlative study relating the MR imaging and pathologic findings was performed. SUBJECTS AND METHODS: Nine high-performance athletes 18-22 years old (mean age, 20 years) underwent operation of 11 knees for long-standing jumper's knee. The average period of symptoms was 3 years (range, 2 to 6 years). MR knee examinations were performed before surgery in all athletes. The symptoms, MR findings, and pathological findings were correlated. RESULTS: There was focal thickening in the proximal one third of the patellar tendon (range, 9-16 mm; mean, 12 mm) in all 11 knees, involving the medial portion of the tendon in 10 and the center in one. On proton-density-weighted MR images, all knees demonstrated a focus of abnormal signal intensity in the proximal one third of the patellar tendon. On T2-weighted MR images, 10 knees demonstrated abnormal signal intensity; eight were isointense to that seen on proton-density-weighted images, and two were relatively hyperintense. Ten tendons demonstrated a poorly defined posterior margin. Pathologically, the areas of abnormal signal intensity corresponded to tissue containing tenocyte hyperplasia, prominent angiogenesis with endothelial hyperplasia, loss of longitudinal collagenous architecture, and microtears with collagen fiber separation. Hyaline degeneration was present in specimens from every patient. CONCLUSION: In athletes with chronic patellar tendinitis, areas of abnormal signal intensity on MR imaging corresponded to degenerative pathologic changes consistent with angiofibroblastic tendinosis. In nearly all patients, the tendon thickening occurred eccentrically. Disproportionate medial tendon thickening may be related to unequal tensile forces across the knee joint, resulting in greater stress on the medial portion of the extensor mechanism of the knee. PMID- 7785570 TI - Abnormalities of the foot and ankle: MR imaging findings. AB - Although plain film radiography remains the appropriate imaging technique used in the initial evaluation of ankle and foot disorders, MR imaging has rapidly become important because it provides high soft-tissue contrast and multiplanar capability, and because it can detect subtle marrow abnormalities. MR imaging is most useful for evaluating pathologic processes that involve soft-tissue structures and for evaluating patients whose clinical findings remain unexplained despite normal findings with other imaging techniques. This pictorial essay illustrates various applications for MR imaging of the foot and ankle. PMID- 7785571 TI - Treatment of high-grade bone sarcomas with neoadjuvant chemotherapy: the utility of sequential color Doppler sonography in predicting histopathologic response. AB - OBJECTIVE: The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing's sarcoma or high-grade osteosarcomas early in treatment. SUBJECTS AND METHODS: Color Doppler flow imaging was done in 31 patients before, during, and after chemotherapy. In each phase of treatment, semiquantitative changes in intratumoral blood flow, changes in maximum intratumoral Doppler shifts, and changes in resistive indexes of arteries feeding limbs that contained tumors relative to contralateral normal arteries were compared with the histopathologic response, as evaluated on the resected specimens. RESULTS: Before chemotherapy, pathologic flow was found in the extraosseous component of all but two patients. Resistive indexes in arteries that fed tumors were significantly lower (p < .001) than the resistive indexes in the contralateral normal arteries. Histopathologic response could not be predicted on the basis of the initial measurements of Doppler shifts and resistive indexes taken before or after the first cycle of chemotherapy. Histopathologic response could be predicted after the second cycle of chemotherapy. After the second cycle of chemotherapy, the resistive index in the arteries that fed tumors increased in eight of nine good respondents but did not change or decreased in eight of nine poor respondents (p = .03). Lower intratumoral Doppler shifts were measured in six of 10 good respondents but also in five of 13 poor respondents (p = .07). After the full course of chemotherapy, persistent lower resistive indexes were measured in the arteries that fed tumors in all poor respondents but one. Intratumoral flow and Doppler shifts further decreased in all good respondents but one. Changes in Doppler shifts (p = .001) and resistive indexes (p < .001) were statistically significant between good and poor respondents, irrespective of the tumor type studied. CONCLUSION: Decreased or unaltered resistive index in the arteries that feed tumors in addition to persistent intratumoral flow and high-frequency Doppler shifts after two cycles of chemotherapy suggest poor histologic response to chemotherapy in osteosarcoma and Ewing's sarcoma. An increased resistive index after two cycles is indicative of good response. PMID- 7785572 TI - Primary bone tumors: value of MR angiography for preoperative planning and monitoring response to chemotherapy. AB - OBJECTIVE: The purposes of our study were to investigate the use of MR angiography with two- (2D) and three-dimensional (3D) displays in evaluating vascular morphology of musculoskeletal neoplasms for preoperative planning of limb-salvage surgery and to assess the use of MR angiography for monitoring changes in neovascularity and evaluating response to chemotherapy. SUBJECTS AND METHODS: We used MR angiography (2D time-of-flight) to study 13 patients with primary bone tumors (nine osteogenic sarcomas, two Ewing's sarcomas, and two primary lymphomas of bone) at the time of initial presentation. Eight patients (all of whom had osteogenic sarcoma) also underwent MR angiography following chemotherapy before limb-salvage surgery. Two-dimensional maximum intensity projections were obtained. Three-dimensional reconstructions of vascular structures were created from the angiographic source images and were displayed simultaneously with 3D reconstructions of tumor and normal bone generated from conventional MR images. RESULTS: Two-dimensional maximum intensity projections were useful for evaluating small vessel neovascularity; 3D displays demonstrated spatial relationships of tumor, feeder vessels, and normal vascular structures. Tumor encroachment onto or encasement of normal vascular structures was shown in four patients on 2D maximum intensity projections and on 3D displays. The eight patients with osteogenic sarcoma who had follow-up imaging showed marked neovascularity prior to chemotherapy. Five patients responded to chemotherapy (> or = 90% tumor necrosis at histology); MR angiography showed marked reduction in tumor neovascularity in these patients. Three patients did not respond to chemotherapy; MR angiography showed unchanged neovascularity in one and increased neovascularity in two of these patients. CONCLUSION: MR angiography provides good visualization of peripheral vascular branches and tumor neovascularity in patients with primary bone tumors. MR angiography demonstrates encroachment onto and encasement of major vessels by the tumor mass and appears to be useful for assessing response to chemotherapy in osteogenic sarcoma and possibly other primary bone tumors by detecting treatment-induced changes in tumor neovascularity. PMID- 7785573 TI - Renal osteodystrophy: imaging findings that mimic those of other diseases. AB - Musculoskeletal complications in patients with chronic renal failure are common and may be related to the disease itself or to treatment. The altered metabolism in patients with chronic renal failure leads to renal osteodystrophy, which consists of osteomalacia and secondary hyperparathyroidism [1]. Erosive changes attributable to secondary hyperparathyroidism may be easily confused with rheumatoid arthritis, seronegative spondyloarthropathies, infection, or even malignancy. Brown tumors and amyloid deposition can easily be mistaken for a neoplastic process. The purpose of this article is to illustrate radiographic findings that are caused by renal failure and that often mimic other diseases by use of plain radiographs, CT scans, and MR images. Particular emphasis is placed on periarticular findings. PMID- 7785574 TI - Estimation of total lung capacity from chest radiography and chest CT in children: comparison with body plethysmography. AB - OBJECTIVE: The purpose of this study was to evaluate two methods of estimating lung volume using chest radiographs and one using chest CT in children. Estimates made with these techniques were compared with total lung capacity calculated with body plethysmography. MATERIALS AND METHODS: CT scans and posteroanterior and lateral radiographs of the chest were obtained in 21 children (14 girls and seven boys) for follow-up evaluation after lung transplantation. Lung volume was measured by CT using a previously validated technique of tracing the margins of the lungs on each axial CT scan. Two methods were used to estimate lung volume on chest radiographs: a technique previously described in adults and children that requires 21 measurements on posteroanterior and lateral radiographs, and a modification of a simplified technique previously reported in adults that uses only two measurements on a posteroanterior radiograph alone. Estimated lung volumes from CT and from both methods using chest radiographs were compared with total lung capacity determined from body plethysmography using regression analysis, and 95% prediction intervals were generated. RESULTS: All three methods of estimating lung volumes from radiographs correlated well with total lung capacity from plethysmography (r = .89-.92). However, we found no statistically significant or clinically meaningful difference among the methods of estimating lung volume. CONCLUSIONS: Lung volumes in children can be accurately estimated from specific measurements made on chest radiographs and on CT scans. Of the two methods tested with chest radiographs, the technique that required only two measurements from a posteroanterior chest radiograph was as accurate as the more complicated technique that required 21 measurements. PMID- 7785576 TI - The role of imaging in patients with ascites. AB - Imaging plays a significant role in patients with ascites for assessing the size and the causes of ascitic fluid, for assisting sampling or draining of ascitic fluid, for selecting candidates for TIPS placement, and for surveilling and detecting complications after TIPS placement. Sonography and CT are primary imaging tools, and MR imaging is used in selected cases such as demonstration of peritoneal or ascitic fluid enhancement, particularly in patients with compromised renal function. Interventional procedures combined with CT and sonography play a major role in the assessment of patients considered for TIPS placement because of refractory esophageal bleeding or ascites. Before the TIPS procedure, these procedures are used to exclude contraindications such as polycystic liver disease, hypervascular hepatic tumors, and portal vein thrombosis. After the TIPS procedure, sonography combined with interventional procedures is used to detect immediate complications such as hemorrhage or intractable shunt-induced encephalopathy due to excessive portosystemic diversion and to detect and treat mid- to long-term complications such as shunt stenosis and occlusion through a routine surveillance program. PMID- 7785577 TI - Sudden death in Marfan syndrome. PMID- 7785575 TI - Lateral ventricular effacement as an isolated sonographic finding in premature infants: prevalence and significance. AB - OBJECTIVE: The sonographic finding of effaced lateral ventricles in premature infants, defined as the absence of visible CSF within the lateral ventricles on both coronal and sagittal sonograms, may be cause to suspect diffuse cerebral edema, especially as published reference standards do not address this phenomenon. This investigation was undertaken to determine the prevalence and significance of effaced lateral ventricles without associated parenchymal abnormality (isolated lateral ventricular effacement, or ILVE) in premature infants. MATERIALS AND METHODS: Sonographic records of 398 consecutive newborns examined from January 1 to December 31, 1993, were reviewed retrospectively to identify those premature infants (< 36 weeks of gestational age) whose initial sonograms showed no evidence of intracranial hemorrhage, ventriculomegaly, structural abnormality, or abnormal parenchymal echogenicity. We identified 142 neonates who met these criteria. Patients were separated into two groups on the basis of whether they had at least one sonographic study in which CSF was not visible within both lateral ventricles on coronal and sagittal images. Medical records were reviewed to assess neurologic outcome. RESULTS: Forty patients (28%) had at least one sonogram demonstrating ILVE, with neurologic follow-up in 33 (representing group A). One hundred two patients (72%) never demonstrated ILVE, with neurologic follow-up established in 86 (representing group B). A comparison of the two groups showed no significant difference in the development of ischemic injury (one patient in each group). ILVE was first detected on the initial sonogram obtained (mean, 4 days) in 30 of the 33 neonates in group A. ILVE was demonstrated beyond the seventh day of life in 30%. Of the 89 patients whose initial sonograms showed CSF in the lateral ventricles (86 in group B and three in group A), three (3%) subsequently had sonograms that showed ILVE; all three were normal at follow-up. CONCLUSION: ILVE in premature infants is common and not associated with neurologic deficits indicative of hypoxic-ischemic encephalopathy. By itself, ILVE is not a significant finding. PMID- 7785578 TI - Portal vein stenosis in children with segmental liver transplants: treatment with percutaneous transhepatic venoplasty. AB - OBJECTIVE: We reviewed the early results of percutaneous portal venoplasty as a method of treating portal vein stenosis in 11 children with reduced-size liver transplants. SUBJECTS AND METHODS: Percutaneous transhepatic portal venoplasty was attempted in 11 children with portal vein stenoses over a period of 9 months. The venoplasty was performed by direct puncture of an intrahepatic portal vein followed by balloon angioplasty of the stenotic segment. Patients presented with symptoms of portal venous hypertension or were identified by routine surveillance with posttransplant Doppler sonography. All stenoses were verified with angiography before portal venoplasty was attempted. In patients with suboptimal results after portal venoplasty or who developed recurrent stenoses, intravascular stents were placed across stenoses. RESULTS: In eight of 11 patients, initial clinical and technical success was achieved. Intravascular stents were placed in two of these patients. In the three unsuccessful procedures, complete occlusion of the portal vein precluded vascular access. Two procedure-related complications and one nonprocedure-related complication developed. In one patient, the portal vein restenosed after 6 months, and a metallic intravascular stent was placed to alleviate the stenosis. Portal vein patency in all other successful procedures has been maintained for 3-9 months (mean, 6.1 months) without further intervention. CONCLUSION: Percutaneous transhepatic portal venoplasty of portal vein stenosis in children with living, related liver transplant donors has excellent early results. In patients with this complication, the procedure has become the initial choice in our hospital, eliminating the need for surgical revision, portacaval shunting, or retransplantation. PMID- 7785580 TI - Sinus pericranii: sonographic findings. PMID- 7785579 TI - The value of portal vein pulsatility on duplex sonograms as a sign of portal hypertension in children with liver disease. AB - OBJECTIVE: The purpose of this study was to determine the significance of portal vein pulsatility on duplex Doppler waveforms in children with end-stage hepatic failure undergoing liver transplantation. SUBJECTS AND METHODS: Thirty-eight children with end-stage hepatic decompensation were examined with color-assisted spectral Doppler waveform analysis of the hepatic artery and the portal vein. Correlation was made with age, duration of illness, clinical and pathologic diagnosis, and presence of portal hypertension. Findings were compared with those for six patients with acute viral hepatitis and 12 healthy control subjects. RESULTS: Portal vein pulsatility was noted in all 36 patients in whom portal vein flow was detected by Doppler imaging. The majority of these (34) had clinical or sonographic evidence of portal hypertension. In two patients, no portal vein flow was identified in the liver hilum; both had a large portosystemic shunt through collaterals or surgical graft. Significantly increased pulsatility of the hepatic artery waveform (resistive index [RI] = 0.89 +/- 0.15, p < .0001) was seen in patients with end-stage liver disease. In contrast, no portal vein pulsatility and normal hepatic artery pulsatility (RI = 0.60 +/- 0.11) was noted in all patients with acute hepatitis and control subjects. CONCLUSION: Portal vein waveform pulsatility is 94% sensitive and 90% specific for portal hypertension in end-stage liver disease. PMID- 7785581 TI - Accuracy of a voice-to-text personal dictation system in the generation of radiology reports. AB - OBJECTIVE: Systems that convert spoken words directly into text have recently become available. The purpose of this study was to test the accuracy, on a word for-word basis, of one such system for generating radiology reports. MATERIALS AND METHODS: The IBM Personal Dictation System (IPDS), with the optional add-on radiology vocabulary, was assessed (the system is now known as VoiceType Dictation). The system requires one to use discrete speech (i.e., with a momentary pause between words). Two hundred current radiology reports, including 100 consecutive chest radiographs, 50 consecutive thoracic CT scans, and 50 random sonography and angiography reports, were read to the system. Before testing, the IPDS had been used in the dictation of material related to chest radiology. All errors were noted on a word-for-word basis and categorized as follows: incorrect, partially incorrect (no effect on meaning), not in dictionary (word was then added), homophone, or formatting. Medical words (those thought to be relevant to the meaning of the report) were considered separately. Specific assessments of numbers and dates were made. Words added to the dictionary were reread after the 200 reports had been assessed. RESULTS: When all mistakes were considered, the accuracy was 0.99 for chest radiology and 0.96 for material not concerning chest radiology. When only relevant mistakes on medical words were considered, the accuracies were 0.98 and 0.96, respectively. Accuracy for numbers was 0.95 and for dates 0.97. Redictation of the 22 words previously not in the dictionary was 100% accurate. CONCLUSION: The IPDS is an accurate system for direct voice-to-text dictation of radiology reports that improves with continued use. The most important future enhancement of such systems will be to allow the more natural continuous or conversational speech style. PMID- 7785582 TI - American martyrs to radiology. Walter James Dodd (1869-1916). 1936. PMID- 7785583 TI - Chest case of the day. Metastatic bronchial carcinoid. PMID- 7785584 TI - Chest case of the day. Hypersensitivity pneumonitis. PMID- 7785585 TI - Chest case of the day. Fibrosing mediastinitis. PMID- 7785586 TI - The mammography audit: a primer for the mammography quality standards act (MQSA). AB - The medical audit of a mammography practice is a recognized method for evaluating mammography and the accuracy of mammographic interpretation [1-4]. As such, portions of the audit will become integral to the quality assurance activities of every mammography practice under the Mammography Quality Standards Act (MQSA) of 1992, administered by the Food and Drug Administration (FDA). The FDA Interim Rules, which became effective October 1, 1994, state that "each facility shall establish a system for reviewing outcome data from all mammography performed, including follow-up on the disposition of positive mammograms and correlation of surgical biopsy results with mammogram reports" [5]. It is expected that the proposed final rules, due to be released for public comment in 1995, will require collection of additional data for medical audits (public meeting of the National Mammography Advisory Committee, May 3, 1994). Although most mammography practices are now collecting clinical outcomes data on abnormal mammographic examinations, very few have established an organized and deliberate system of data collection necessary for a more complete mammography audit [6]. A detailed discussion of and recommendations for such an audit were recently published as part of the Quality Determinants of Mammography Guideline by the Agency for Healthcare Policy and Research (AHCPR) [7]. As members and consultants on the multidisciplinary panel that produced the guideline, we offer the following review of the various elements, definitions, and processes of the mammography audit. This is intended as a primer for all radiologists who will be performing some of the same audit activities for the MQSA. PMID- 7785587 TI - Chest case of the day. Williams-Campbell syndrome. PMID- 7785588 TI - Gastrointestinal case of the day. Obturator hernia causing small bowel obstruction. PMID- 7785590 TI - Gastrointestinal case of the day. Mirizzi syndrome. PMID- 7785591 TI - Gastrointestinal case of the day. Cystic fibrosis with colonic intussusception. PMID- 7785589 TI - Gastrointestinal case of the day. Systemic mastocytosis. PMID- 7785592 TI - Genitourinary case of the day. Renal lymphangiomatosis. PMID- 7785593 TI - Genitourinary case of the day. Angiomyolipoma of the kidney with fat thrombus in the inferior vena cava. PMID- 7785594 TI - Genitourinary case of the day. Renal tuberculosis. PMID- 7785595 TI - Genitourinary case of the day. Replacement lipomatosis of the kidney. PMID- 7785596 TI - Musculoskeletal case of the day. Giant cell tumor of the sacrum. PMID- 7785597 TI - Musculoskeletal case of the day. Sarcomatous degeneration of Paget disease. PMID- 7785598 TI - Musculoskeletal case of the day. Periosteal (juxtacortical) chondroma. PMID- 7785600 TI - Pediatric radiology case of the day. Peritoneal carcinomatosis. PMID- 7785601 TI - Pediatric radiology case of the day. Congenital goiter secondary to inherited thyroid dyshormonogenesis. PMID- 7785599 TI - Musculoskeletal case of the day. Tuberculous sacroiliitis. PMID- 7785603 TI - Pediatric radiology case of the day. Disseminated neonatal hemangiomatosis. PMID- 7785604 TI - Neuroradiology case of the day. Von Hippel-Lindau disease. PMID- 7785602 TI - Pediatric radiology case of the day. Multifocal infantile fibromatosis. PMID- 7785606 TI - Neuroradiology case of the day. Gliomatosis cerebri. PMID- 7785605 TI - Neuroradiology case of the day. Enhancing calcified hematoma due to prior hypertensive bleed. PMID- 7785608 TI - What technique should I try if spontaneous reflux does not occur? PMID- 7785607 TI - Neuroradiology case of the day. Multifocal inflammatory leukoencephalopathy due to treatment with 5-fluorouracil and levamisole. PMID- 7785609 TI - What is the simplest and most easily monitored regimen of sedation for CT and MR in children in a setting in which only occasional outpatients are scanned? PMID- 7785610 TI - Which is the most sensitive study for testicular torsion in children--Doppler sonography or testicular nuclear scan? PMID- 7785611 TI - When should you use contrast agents for CT of the head? PMID- 7785612 TI - What MR sequences should be used in the evaluation of pulsatile tinnitus? PMID- 7785613 TI - Focal anterior mediastinal fibrosis following median sternotomy. PMID- 7785614 TI - Liquefaction of thrombus in thoracic aortic aneurysm: MR findings. PMID- 7785615 TI - Traumatic pneumatocele as a complication of guidewire manipulation. PMID- 7785616 TI - Minimizing repeat mammography. PMID- 7785617 TI - Granular cell tumor of the breast in a male. PMID- 7785619 TI - Primary hepatic actinomycosis: association with portal vein thrombosis. PMID- 7785620 TI - Schwannoma arising from peripancreatic nerve plexus. PMID- 7785618 TI - Surgical injury of the common bile duct. PMID- 7785622 TI - Scalp lipogranuloma due to dermal lipid injections: CT and MR findings. PMID- 7785621 TI - MR appearance of intratesticular varicocele. PMID- 7785624 TI - Re: Advances in perinatal neurosonography. PMID- 7785623 TI - Carotid artery stenosis: old measurement for new technology? PMID- 7785625 TI - Triage of patients to angiography for detection of aortic rupture after blunt chest trauma: cost-effectiveness analysis of using CT. AB - OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of dynamic chest CT, compared with plain chest radiography and immediate angiography, in deciding when angiography should be performed in hemodynamically stable patients with suspected aortic rupture after blunt chest trauma. The use of CT was evaluated in relation to the prior probability of aortic rupture. MATERIALS AND METHODS: A cost-effectiveness analysis comparing six diagnostic strategies combining chest radiography, CT, and angiography in various sequences was performed. Effectiveness was expressed as survival to hospital discharge, and costs were those incurred to society. Estimates for the variables in the analysis were derived from published reports. The model was evaluated for two cohorts of patients: those undergoing and those not undergoing CT for the evaluation of other injuries. Sensitivity analysis was performed for all variables in the model with emphasis on the prior probability of aortic rupture. RESULTS: Selecting patients for triage to angiography based on the CT findings yielded higher effectiveness at a lower cost-effectiveness ratio than doing so based on the chest radiograph, and the incremental cost-effectiveness ratio was less than $500,000 per life saved. For the cohort undergoing CT for the evaluation of other injuries, triage to angiography based on the CT findings yielded equivalent survival chances compared with immediate angiography and cost less ($1468 per patient evaluated compared with $2508). For the cohort not undergoing CT for other injuries, immediate angiography yielded the highest survival chances but was expensive, with an incremental cost-effectiveness ratio of $2 million per life saved compared with triage based on CT. In the latter cohort, immediate angiography yielded higher survival chances and had a cost-effectiveness ratio of less than $500,000 compared with the triage by CT if the prior probability of aortic rupture was 5% or more. CONCLUSION: Selecting hemodynamically stable patients after blunt chest trauma with suspected aortic rupture for angiography on the basis of CT findings is more effective than doing so based on the findings on chest radiography and is cost-effective compared with other accepted health care programs. Immediate angiography has a high incremental cost-effectiveness ratio compared with triage by CT and is warranted only in patients not undergoing CT for the evaluation of other injuries who have a prior probability of aortic rupture of 5% or more. PMID- 7785626 TI - Radiology decision making: the importance of cost-effectiveness analysis. PMID- 7785627 TI - Radiology in Lithuania: impressions of a visiting professor. AB - In the fall of 1993, I had the privilege of spending 3 months as a Radiological Society of North America (RSNA) International Visiting Professor at the Kaunas Medical Academy in Lithuania. This visiting professor program was started in 1986 and is funded by the RSNA Research and Education Fund [1]. It is designed for a visiting professor who can spend 3 months or longer at a radiology residency training program in an evolving country. Lithuania, with a population of about 4 million, is located on the eastern shore of the Baltic Sea, just north of Poland. The land area is approximately equal to that of Switzerland. An independent country until World War II, when it was forcibly occupied and integrated into the Soviet Union, it regained independence in 1990. As a result of 50 years of communist rule, two generations grew up having little knowledge about Western medicine in general and radiology in particular. A communist legacy is still evident not only in education but also in the thought process of the people, although there is a clear desire to integrate into western Europe. Currently Western and Asian consumer goods are readily available, but the country has undergone steep inflation and it is the perception of many that the standard of living continues to decline. PMID- 7785628 TI - Grandpa takes the boards. PMID- 7785629 TI - Detection of pneumoperitoneum on chest radiographs: comparison of upright lateral and posteroanterior projections. AB - OBJECTIVE: This study was done to determine whether upright lateral chest radiographs were more sensitive than upright posteroanterior chest radiographs in detecting pneumoperitoneum. SUBJECTS AND METHODS: We prospectively evaluated the ability of upright posteroanterior and lateral chest radiographs to show subdiaphragmatic air in 100 consecutive patients with known pneumoperitoneum from a variety of causes. The difference in sensitivity between the two was evaluated by means of McNemar's test. RESULTS: The upright lateral chest radiograph showed pneumoperitoneum in 98% of the cases; the upright posteroanterior chest radiograph showed pneumoperitoneum in only 80%. The upright lateral chest radiograph was significantly better at showing pneumoperitoneum than was the upright posteroanterior chest radiograph (p < .01). CONCLUSION: The upright lateral chest radiograph is more sensitive than the upright posteroanterior chest radiograph in detecting small amounts of pneumoperitoneum. When there is a strong clinical suspicion of a perforated hollow viscus, it may be of benefit to include an erect lateral chest radiograph as part of the acute abdominal series. PMID- 7785630 TI - Pulmonary lymphangitic carcinomatosis: chronicity of radiographic findings in long-term survivors. AB - OBJECTIVE: Long-term survival after development of pulmonary lymphangitic carcinomatosis is considered unusual. However, modern chemotherapy can result in surprising stability or only gradual progression of lymphangitic carcinomatosis. We evaluated the course of radiographic findings in 10 patients with chronic lymphangitic carcinomatosis. MATERIALS AND METHODS: Ten patients met our criterion of having lymphangitic carcinomatosis for at least 6 months. The primary tumor was a carcinoma of the breast in six cases, the ovary in two, the pancreas in one, and the skin in one. Serial radiographs (all cases) and CT scans (eight cases) were analyzed retrospectively. RESULTS: Survival with lymphangitic carcinomatosis ranged from 11 to 30 months (median, 13 months). With chemotherapy, the radiographic abnormalities and pulmonary symptoms initially regressed in six patients, progressed in two, and remained unchanged in two; the radiographic findings of lymphangitic carcinomatosis were progressing at the time of death in four patients. All patients had periods of at least 4 months of relative stability or slow progression of pulmonary radiographic abnormalities. Serial transbronchial biopsies in one case confirmed persistent lymphangitic carcinomatosis despite therapy, and autopsy disclosed persistent lymphangitic tumor in two others. CONCLUSION: Stability or slow progression of radiographic findings can occur in some patients with lymphangitic carcinomatosis. Therefore, chronicity of radiographic findings should not be taken as evidence against lymphangitic carcinomatosis as the cause of an interstitial abnormality in a patient with cancer. PMID- 7785631 TI - CT-guided automated needle biopsy of the chest. AB - OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy and frequency of complications of CT-guided transthoracic needle biopsy done with an automated biopsy system. MATERIALS AND METHODS: Thirty-three consecutive biopsies were performed on 32 patients between February 1992 and July 1994 (mean age, 55 +/- 15 years; 18 men and 14 women). An 18-gauge (n = 28) or 20-gauge (n = 5) needle was used. Core specimens were submitted for pathologic examination in 10% formalin. No cytopathologist or frozen section analysis was available at the time of biopsy. All biopsies but one were performed by one chest radiologist. RESULTS: Thirty-one lung biopsies and two mediastinal biopsies yielded a mean lesion size of 4.0 cm (range, 1.2-13.0 cm). Postbiopsy pneumothorax occurred in three (9%) of 33 biopsies; none of the pneumothoraces required placement of a chest tube. The mean number of needle passes was 1.3 (+/- 0.6). Thirty biopsies (91%) yielded sufficient tissue for pathologic evaluation. The diagnoses included carcinoma in 14 cases, acute or chronic pneumonia in 4 cases, non-Hodgkin's lymphoma in two cases, and Kaposi's sarcoma, plasma cell granuloma, hypersensitivity pneumonitis, Pneumocystis carinii pneumonia, and fibrosis in one case each. One patient with a 1.5-cm nodule stable for 1 year on CT had fibrosis and chronic inflammation found on needle biopsy, and the nodule was considered benign. Overall, biopsies in 12 (80%) of 15 patients without carcinoma were diagnostic. In three patients, the tissue obtained was not representative of the underlying abnormality. The biopsy specimen showed only inflammatory changes in two patients who ultimately had proved carcinoma. One patient with multiple pulmonary infarcts due to tumor emboli showed evidence of only pulmonary infarct on biopsy. Three patients had insufficient tissue for analysis; none of the three had malignant tumor on follow up. The sensitivity of CT-guided automated needle biopsy of the chest was 84%. CONCLUSION: CT-guided transthoracic needle biopsy of the chest done with an automated biopsy system is safe, with a pneumothorax rate comparable to that of skinny needle aspiration. An overall accurate tissue diagnosis was made in 26 (81%) of 32 patients. Biopsies in 12 (80%) of 15 patients without carcinoma were diagnostic, which compares favorably with the reported accuracy of skinny needle aspiration. PMID- 7785632 TI - Thoracic bacillary angiomatosis in a patient with AIDS. PMID- 7785633 TI - Mammography immediately after stereotaxic breast biopsy: is it necessary? AB - OBJECTIVE: The purpose of this study was to determine whether mammography immediately after stereotaxic core breast biopsy should be performed routinely to diagnose hematoma, to confirm the sampling site, and to establish a new baseline for future mammograms. MATERIALS AND METHODS: Stereotaxic core biopsies of 113 mammographically indeterminate or suspicious lesions were performed by use of a dedicated stereotaxic table with digital imaging, a 14-gauge needle, and an automated gun. The indication for biopsy was a mass with or without calcifications in 59 cases (52%) and calcifications without a mass in 54 cases (48%). The number of core biopsies per case ranged from one to 16 (mean = six). Craniocaudal and mediolateral oblique mammograms of the sampled breast were obtained immediately after the biopsies and were compared with prebiopsy mammograms. In cases with microcalcifications, the mammograms also were compared with specimen radiographs. RESULTS: Mammograms obtained immediately after the procedure showed changes related to the biopsy in 86 cases (76%). These findings included decreased lesion size in 11 (10%), air at the biopsy site in 47 (42%), and hematoma, manifested as poorly defined increased density at the biopsy site, in 58 (51%). One hematoma was clinically significant, but the remaining 57 were clinically occult. When core biopsies were performed for calcifications, the postprocedural mammograms showed a decrease in the number of calcifications in 26 (48%) of 54 cases, but specimen radiographs showed calcium in 50 (93%) of 54 cases. Four lesions (three masses and one cluster of microcalcifications) disappeared after biopsy. In three cases, hematomas obscured residual calcifications at the biopsy site. CONCLUSION: Mammography immediately after core biopsy is not necessary for the diagnosis of procedure-related hematoma and is inferior to specimen radiography for verifying that calcifications have been sampled. Postprocedural mammograms also may be suboptimal for the establishment of a new baseline because of the frequent finding of hematoma. PMID- 7785634 TI - Granular cell tumor of the breast in a male patient. PMID- 7785635 TI - Medullary thyroid carcinoma metastatic to the breast: mammographic appearance. PMID- 7785636 TI - Cytomegalovirus colitis in AIDS: CT features. AB - OBJECTIVE: The purpose of this study was to determine the CT features of cytomegalovirus colitis in patients with AIDS. MATERIALS AND METHODS: Abdominal CT scans of 24 patients with biopsy-proved cytomegalovirus colitis (colonoscopy, n = 14; sigmoidoscopy, n = 8; surgery, n = 2) were jointly reviewed by two observers. Patients were men 26-68 years old (mean age, 39 years; SD, 9 years) with CD4 counts of 3-129 mm3 (mean, 32 mm3; SD, 34 mm3). The mean interval between CT and biopsy was 6 days (range, 0-20 days; SD, 6 days). Scans were assessed for colonic wall thickening (> or = 4 mm), ulceration, mural edema, pericolonic stranding, ascites, lymphadenopathy, and thickening of the small bowel wall. Mural involvement was recorded as asymmetric or circumferential. Disease location was recorded as ascending colon, transverse colon, descending colon, rectosigmoid colon, or pancolonic. RESULTS: Colonic wall thickening of 8 to 33 mm (mean, 15 mm; SD, 6 mm) was seen in 22 patients. One patient had pancolonic involvement. The ascending colon was involved in 13, the transverse colon in five, the descending colon in 10, and the rectosigmoid colon in 16. Circumferential colonic thickening was seen in 17 patients. Deep mural ulceration was seen in 15 patients, mural edema in 15, pericolonic stranding in 23, ascites in 10, lymphadenopathy in four, and small-bowel involvement in 10. Two patients had appendicitis. Three patients had perforations (two rectal, one cecal). One patient had a giant rectal ulcer. CONCLUSION: Although many of the CT features of cytomegalovirus colitis are nonspecific, the diagnosis should be suggested when CT shows colonic wall thickening, particularly if the thickening is associated with mural ulceration in patients with AIDS and CD4 counts of less than 200 mm3. PMID- 7785637 TI - Helical CT of the liver: clinical application of an automated computer technique, SmartPrep, for obtaining images with optimal contrast enhancement. AB - OBJECTIVES: The purpose of this study was to evaluate an automated computer technique (SmartPrep) for achieving a consistently high level of contrast enhancement in the liver with helical CT. The technique compensates for variability between patients by indicating graphically the time at which scanning should be initiated to reach a desired level of hepatic enhancement. MATERIALS AND METHODS: One hundred nine consecutive patients undergoing helical CT of the abdomen were randomly evaluated, using either a standard 70-sec delay from the start of the injection of contrast material to scanning or a newly developed, commercially available automated technique, SmartPrep. A series of multiple low dose scans was performed until an arbitrary threshold of hepatic enhancement (50 H) over baseline was achieved. Three regions of interest (ROIs) were imaged on a baseline scan and on contrast-enhanced scans at the upper, mid, and lower liver. Average hepatic enhancement and the standard deviation over baseline was calculated for each group at all anatomic levels. For the SmartPrep group, the range of time between scan initiation and onset of scanning was calculated. RESULTS: The mean hepatic enhancement for the control group (n = 56) was 59.8 +/- 20.1 H, which differed significantly (p = .0002) from that for the SmartPrep group (n = 53), which was 71.6 +/- 15.2 H. Comparison of the variability between the two groups' enhancement levels was also significant (p = .02). The range of delay times for the SmartPrep group was 48-86 sec. In two additional cases, abnormal graphically displayed enhancement curves were the first indication of an improper injection. CONCLUSION: Use of SmartPrep yields a greater and more consistent level of hepatic enhancement from patient to patient than does use of a conventional fixed delay time. The ability to scan more efficiently to achieve greater hepatic enhancement using SmartPrep has significant implications for potential contrast cost savings. PMID- 7785639 TI - Base hospital. PMID- 7785638 TI - High-dose localized radiation therapy for treatment of hepatic malignant tumors: CT findings and their relation to radiation hepatitis. AB - OBJECTIVE: High-dose radiation therapy of the liver performed using overlapping portals defined by a three-dimensional treatment-planning system (conformal radiation therapy) is a new method of treating hepatic tumors. This study was performed to delineate the differences in the CT appearances of the liver after therapy compared with other methods of radiotherapy and to correlate imaging findings to clinical findings of radiation hepatitis. MATERIALS AND METHODS: Contrast-enhanced CT scans were obtained at 8- to 12-week intervals on 31 consecutive patients with primary or metastatic hepatic malignant tumors. All had undergone high-dose conformal radiation therapy and injection of fluorodeoxyuridine into the hepatic artery as part of the treatment for unresectable hepatic neoplasms. Tumor size, location, presence of changes within the target volume after therapy, presence of atrophy of the treated segments or hypertrophy of the untreated segments, ascites, and any changes in adjacent organs seen on serial CT scans obtained before and after treatment were recorded. Clinical records were reviewed for evidence of radiation hepatitis (nonmalignant ascites evident on physical examination and a twofold elevation of alkaline phosphatase in the anicteric patient). RESULTS: In 23 (74%) of the 31 patients, follow-up CT studies after treatment showed a low-attenuation area adjacent to the hepatic tumor in the target volume. In two patients with fatty infiltration of the liver, CT showed relative increased density in the treatment portal. A sharp, straight interface was rarely seen at the treatment margin. Maximal effect was seen 2-3 months after completion of therapy and persisted for up to 3 months. Atrophy in the treated segment or lobe was seen in four patients, hypertrophy of the untreated liver was seen in four patients, and both effects were seen in seven patients. Extrahepatic effects included segmental right renal atrophy in three patients and duodenal wall thickening in two patients. Only two patients (6%) in this series had clinical evidence of radiation hepatitis. CONCLUSION: High-dose localized radiotherapy of the liver results in reversible hypodense regions in the liver parenchyma within the target volume that do not have a sharp interface delineating the radiation portal. This appearance should not be confused with tumor progression or irreversible liver injury. The changes evident on CT scans after therapy are not predictive of radiation hepatitis. PMID- 7785640 TI - Acute cholecystitis in an animal model: findings on color Doppler sonography. AB - OBJECTIVE: The purpose of our study was to evaluate the color Doppler findings of acute cholecystitis in a controlled canine model. MATERIALS AND METHODS: Fourteen animals had a laparotomy: cystic duct ligation was done in eight, and incision with closure was performed in six control subjects. Animals were scanned in a blinded fashion preoperatively, immediately postoperatively, and on postoperative days 1-5. On postoperative day 5, a hepatobiliary scan was done with 2 mCi (74 MBq) 99mTc-mebrofenin. Blinded histopathology was performed and correlated with imaging. RESULTS: Flow was seen in the wall of each gallbladder at some point during the postoperative course, demonstrating vascular patency. Hepatobiliary scintigraphy confirmed cystic duct status in 12 cases; two animals died before radionuclide imaging was complete. Color Doppler signal decreased in the gallbladder wall in ligated dogs from postoperative day 1 to postoperative day 3 (p = .03 versus controls at postoperative day 2) and increasingly returned by postoperative day 5. Hyperemia was seen in only two cases (both with severe necrotizing cholecystitis) and only at postoperative day 5. Although not statistically significant, a weak trend of increasing flow with more severe pathologic grades of cholecystitis was observed (p = .20). CONCLUSIONS: In this animal model, loss of vascular signal (not hyperemia) at postoperative day 2 was the finding to diagnose early acute cholecystitis, although lack of flow can also be seen in some normal subjects. Flow tended to return by postoperative day 5, and it increased in some of the more severe cases of cholecystitis. Hyperemia was a somewhat useful sign of acute necrotizing cholecystitis. PMID- 7785641 TI - Diagnosis and management of ascites in the age of TIPS. AB - In the mid 1990s, radiologists are asked to provide advice on managing patients with cirrhosis and refractory ascites. Liver disease is the most common cause of ascites. However, appropriate management of these patients is based on the ability to exclude other causes as well as knowledge of the physiological abnormalities that result in ascites. The goal of this review is to summarize advances in these areas as well as to discuss therapeutic options. PMID- 7785642 TI - Characterization of adrenal masses (< 5 cm) by use of chemical shift MR imaging: observer performance versus quantitative measures. AB - OBJECTIVE: The purposes of this study were to evaluate the ability of chemical shift MR imaging to differentiate 1- to 5-cm adrenal adenomas from metastases and to compare subjective interpretation with several different quantitative measures. SUBJECTS AND METHODS: Forty-three patients with 46 proved adrenal lesions (28 adenomas and 18 metastases) had MR imaging with a gradient-echo breath-hold technique and echo time varied to obtain in-phase and out-of-phase images. Qualitative analysis of the MR images was done by three experienced observers, who reported their confidence in diagnosing the benignity versus the malignancy of the adrenal masses on the basis of signal loss on out-of-phase images. Quantitative analysis was performed by calculating the difference in signal intensity between in-phase and out-of-phase images by use of regions of interest (signal intensity index) and by use of adrenal-liver, adrenal-spleen, and adrenal-muscle signal intensity ratios. Results between quantitative and qualitative measures were compared by use of receiver operating characteristic (ROC) analysis. RESULTS: The mean signal intensity was significantly different between adenomas and metastases on out-of-phase images (64 versus 98) (p < .0005) but not in-phase images (130 versus 122) (p = .47). The adrenal-spleen ratio discriminated between adenomas and metastases better than did the adrenal-liver ratio, the adrenal-muscle ratio, or the signal intensity index. No significant difference in interpretation among the three observers was evident (areas under the ROC curves, 0.93, 0.95, and 0.96). The performance of the observers was comparable to the results obtained with the adrenal-spleen ratio measurement (area under the ROC curve, 0.97). CONCLUSION: Experienced observers were able to differentiate adrenal adenomas from metastases just as well as quantitative measures. The adrenal-spleen ratio is the best quantitative means of distinguishing benign from malignant adrenal masses. Chemical shift MR imaging is a good but imperfect discriminator of adrenal adenomas. PMID- 7785645 TI - A case of lumbar hernia occurring through surgical defect of iliac crest. AB - Hernias occurring in the lumbar area are rare. The lumbar area is a broad anatomic area bordered superiorly by the 12th rib, interiorly by iliac crest, medially by the erector spinae muscle and laterally by the external oblique muscle. Acquired hernias occurring in the lumbar area are often diffuse and grotesque appearing and most of them are post operative incisional hernias occurring in nephrectomy incisions. Rarely hernias occur through bicortical surgical defect of iliac crest. We would like to present such a case and review the literature briefly. PMID- 7785644 TI - Fatal post-cesarean endometritis: report of two Alabama cases. AB - Postpartum endometritis remains a major cause of morbidity in the puerperium with a fatal outcome on occasion. We present two cases of fatal, post-cesarean endometritis which occurred within a fifteen month period in Alabama. We discuss the features of endometritis including pathophysiology, causative organisms, risk factors and complications. PMID- 7785643 TI - Percutaneous balloon catheter dilatation of benign ureteral strictures: effect of multiple dilatation procedures on long-term patency. AB - OBJECTIVE: The purpose of this study was to evaluate the long-term efficacy of multiple percutaneous balloon dilatations of benign ureteral strictures. Percutaneous dilatation of ureteral strictures with a balloon catheter was done as an alternative to open surgical repair. MATERIAL AND METHODS: Twenty-eight benign ureteral strictures (in 23 patients) were dilated. These included 21 postoperative strictures, 18 of which were at ureteroenteric anastomosis, three postradiation strictures, and four strictures of unknown origin. If the stenosis persisted, dilatation was repeated (maximum of four dilatations at 1-month intervals). Patients were reevaluated with sonography at 1-month intervals after stent removal. RESULTS: The procedure was considered a technical success if there was no radiographic evidence of a stricture or if hydronephrosis improved on the sonographic examination. Clinical success was determined by stable or improved renal function. All dilatations were technically successful. Fifteen (54%) of the 28 ureters remained patent 1 month after the final dilatation and removal of the stent. Of these 15, 12 were patent 2 months after stent removal, and only five were free of stenosis at the 9-month follow-up, making overall success 18%. All five of these ureters were in the subgroup of patients with ureteroenteric strictures. CONCLUSION: Balloon dilatation of ureteral strictures is technically successful; however, long-term results are poor. Multiple dilatations are of no benefit in maintaining ureteral patency. PMID- 7785646 TI - The real contract with America. PMID- 7785647 TI - Reactive tumor-like lesions of the peritoneum. PMID- 7785649 TI - The role of pathologists in cancer patient staging. Cancer Committee. PMID- 7785650 TI - Vernix caseosa peritonitis. An infrequent complication of cesarean section with distinctive histopathologic features. AB - The authors report two cases of vernix caseosa peritonitis, an infrequent complication of cesarean section with distinctive histopathologic findings. Both patients underwent exploratory laparotomy for unexplained abdominal pain after cesarean section. Histopathologic evaluation of surgically removed tissue revealed an organizing peritonitis, which included prominent collections of anucleate squamous cells in association with a foreign body-type granulomatous response. In both cases, the surgical pathologist suggested that the abdominal pain was likely a result of peritoneal reaction to spillage of keratinous material (vernix caseosa) derived from amniotic fluid contents during cesarean section. Surgical pathologists should be aware of this entity and include it in the differential diagnosis of acute abdominal pain. PMID- 7785651 TI - Hamartoma of the breast, an underrecognized breast lesion. A clinicopathologic and radiographic study of 25 cases. AB - This study investigated the clinical, radiographic, and pathologic features of breast hamartoma. The patients ranged in age from 18 to 89 years, with a mean age of 45 years, and a median age of 43 years. Seventy-five percent of the patients were asymptomatic, other than reporting a breast lump. In two patients, the lesions recurred at 7 and 18 months after the initial resection. The clinical diagnoses were fibroadenoma in 10 cases, carcinoma in 5 cases, hamartoma in 4 cases, and phyllodes tumor and lipoma in 2 other cases. Mammograms were available in 12 cases, the majority of which showed a well-defined mass of homogeneous density. Grossly, these lesions were oval to round, well-circumscribed masses, ranging in size from 1 to 7 cm in maximum dimension (mean, 3.9 cm). The microscopic appearance of these tumors corresponded to their gross appearance. Lesions that were grossly firm, rubbery, and white consisted largely of dense fibroconnective tissue with variable amounts of glandular elements with little adipose tissue. Softer, pale, yellow lesions contained more adipose tissue. A consistent and important diagnostic feature was the presence of both lobules and ducts, in contrast to fibroadenoma in which lobules are often absent or rare. The current trend of mammographic breast screening has made us aware that mammary hamartomas are not uncommon. These lesions may go unrecognized by the pathologists because they show all the constituents of normal breast tissue and may be reported as "no pathological diagnosis" or "normal breast tissue," which are inappropriate diagnoses for a lesion that presents as a palpable and a well circumscribed mass. PMID- 7785648 TI - Clinical laboratory informatics, the promised land. Are we there yet? PMID- 7785652 TI - Assessment of histopathologic changes in the colonic biopsy in acute graft-versus host disease. AB - The authors reviewed 78 colonic biopsies from 63 patients undergoing bone marrow transplantation (BMT), 56 allogeneic and 7 autologous, to assess different morphologic changes related with intestinal acute graft-versus-host disease (A GVHD). Only five biopsies were done before the 20th day after BMT. The authors studied the presence of ulcers and atrophy in the mucosa, the nuclear atypia, and inflammatory infiltrate in the surface epithelium, and the architectural abnormalities, as well as dilation of the glands, and the presence of crypt abscesses. The authors explored the glandular epithelium for apoptosis and intraepithelial lymphocytes. They examined the lamina propria for inflammatory infiltrate, especially for so-called "focal periglandular infiltrate (FPGI)," edema fibrosis, increase of capillary vessels and presence of muciphages and clusters of enterochromaffin cells. Cases were grouped according to clinical symptoms and histologic diagnosis of A-GVHD in skin or liver. Group A had 15 asymptomatic cases (control). Group B had 20 cases from asymptomatic patients with a histologically proven A-GVHD. Group C had 43 cases with gastrointestinal symptoms and histologically proven A-GVHD. Then, the relative frequency of every histologic feature previously described were compared in the different groups by means of an univariate analysis. Apoptosis of the glandular epithelium was found in 48 cases, two of them in patients carrying an auto-BMT. Focal periglandular infiltrate was found in 11 cases that was associated with apoptosis (P < .03, Fisher's exact test). In this series, the presence of FPGI was linked with finding apoptosis in a given specimen with a probability of 91%. Glandular architectural changes and dilation were also more frequent in group C than in groups A and B when compared in the univariate analysis. PMID- 7785653 TI - Intraneural perineurioma. A clonal neoplasm associated with abnormalities of chromosome 22. AB - The nature of perineurioma, variably termed "localized hypertrophic neuropathy," "intraneural neurofibroma," and "hypertrophic interstitial neuritis" has long been an issue of contention. Most authors consider it a neoplasm, but some a reactive process. Eight clinically and morphologically typical perineuriomas were studied by histologic, immunohistochemical and ultrastructural methods. One perineurioma was subject to tissue culture and cytogenetic study and another to fluorescence in situ hybridization (FISH) analysis. The patients, 3 males and 5 females, ranged in age from 11 to 38 years. All tumors were intraneural, and involved extremities (2 sciatic, 1 median, 1 femoral, 1 peroneal, 1 brachial plexus, 1 ulnar, and 1 radial). Neurologic symptoms, motor in all cases and sensory in 4, were present from 1 month to 7 years (mean 1.2 years). Fusiform, segmental nerve enlargement was clinically apparent in only two patients, but was evident on MRI in five of eight patients. Lesion length ranged from 3.5 to 30 cm, the largest involving the sciatic nerve from the obturator foramen to the knee. One lesion involved two nerve roots, but no association with a phakomatosis was noted. Treatment consisted of biopsy in six cases and resection in two cases. Histologically, pseudo-onion bulbs composed of epithelial membrane antigen reactive, S-100 protein-negative perineurial cells surrounded myelinated or nonmyelinated nerve fibers. Many were accompanied by their S-100 protein-positive Schwann sheaths. Some whorls lacked a central axon. A single mitosis was noted in one case. The MIB-1 antigen labelling index ranged from 4% to 17%. Staining for p53 antigen in six cases showed no (2 of 6), rare (2 of 6), or scattered (2 of 6) immunoreactive nuclei. Cytogenetic analysis in one case demonstrated a chromosomally abnormal clone. Each of 16 metaphases was abnormal; the tumor cells appeared to be homozygously deficient for the region 22q11.2qter. In another case, 53% of interphase nuclei showed three FISH signals with a chromosome 14/22 probe, thus suggesting either monosomy for the centromere of chromosome 14 or that of chromosome 22.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7785654 TI - Protoplasmic astrocytoma. A clinicopathologic study of 16 tumors. AB - Protoplasmic astrocytomas, composed of process-poor astrocytic cells and a microcystic background, are rare variants of low grade astrocytoma. Three hundred eight low grade astrocytomas over a 23-year period were reviewed. Sixteen (5.2%) were classified as pure protoplasmic astrocytoma. Patients (12 males, 4 females) ranged in age from 2.5 to 41 years (mean, 20.7 years). All patients presented with seizures and three had headaches. Duration of symptoms ranged from 7 months to 28 years (mean, 6.6 years). Nine tumors (56%) were left-sided and seven right sided (44%). Seven (44%) occurred in the temporal lobe, six (37%) in the frontal lobe, two (13%) in the parietal lobe, and one (6%) in the thalamus. Surgery consisted of partial lobectomy with total tumor resection in nine and biopsy alone in seven. Five patients received adjuvant therapy with no apparent effect on survival. At frozen section, protoplasmic astrocytoma was most confused with fibrillary low grade astrocytoma (n = 6). Follow-up revealed 10 patients with no evidence of disease 2 to 108 months postoperatively (mean, 41 months), 5 patients were alive with disease 10 to 84 months postoperatively (mean, 56 months) and 1 patient died with disease at 36 months. Of patients with total tumor resection, eight had no evidence of disease and one died with disease. IN CONCLUSION: (1) protoplasmic astrocytomas in this study were more frequently observed in males at a younger mean age than fibrillary low grade astrocytomas as reported in literature; (2) temporal and frontal lobes were the most likely site of origin; and (3) complete excision may be beneficial, whereas adjuvant therapy appeared to have no effect on outcome. PMID- 7785655 TI - Identification of patients for pharmacologic review by computer analysis of clinical laboratory drug concentration data. AB - Clinical pharmacokinetics evaluation and consultation can improve drug therapy and decrease the incidence of adverse reactions in selected patients. However, identification of patients appropriate for review is difficult. The authors developed a microcomputer-based expert system that scans clinical laboratory drug concentration data to identify patients for follow-up. Rules were developed from a review of data for digoxin, phenytoin, and theophylline. These were implemented in software that provides for simple rule creation and modification, on-screen graphic review of data, and printing of chart reports. This program is readily adapted for use with most laboratory information systems. In a retrospective study of 868 patients monitored for digoxin, phenytoin, and theophylline, 29% were flagged as having drug level profiles of possible concern. The majority (62%) of these patients had multiple specimens flagged, suggesting persistent problems. These data suggest that patients can be identified for follow-up by scanning serial drug concentrations, allowing consultative resources to be focused on patients most likely to benefit from them. PMID- 7785656 TI - A strategy to promote rational clinical chemistry test utilization. AB - There is abundant evidence that clinical chemistry laboratory tests are over ordered in North America, but there does not seem to be an effective corrective strategy that has a prolonged effect. The goal of this study was to design one that had a prolonged effect. Using a pre- and post-intervention survey study design, the authors observed the effect of physician education followed by a ban on test-panel ordering of common clinical chemistry tests, reinforced by written reminders to physicians not heeding the ban, on ordering patterns (tests per specimen), and total numbers of these tests ordered. Panels of > 16 common biochemistry tests per specimen were reduced from 15% to 6% of orders for inpatients and from 44% to 11% for outpatients 1 year after the implementation of the ban on test-panel ordering. However, the ban had little effect on the ordering rates for panels of 7 common tests. Educational exercises (newsletters and lectures) had no effect. The authors conclude that a ban on test-panel (profile) ordering reinforced by continuing reminders to nonconforming physicians is an effective means of reducing clinical chemistry test usage over the long term. A 38% reduction of common biochemistry tests ordered was achieved. However, overall costs savings were modest. Nevertheless, the authors conclude that the cost-effective use of the clinical pathology laboratory by careful selection of tests in an essential part of a medical trainee's education. PMID- 7785657 TI - Is myoglobin useful in the diagnosis of acute myocardial infarction in the emergency department setting? AB - The authors evaluated the usefulness of a rapid fluorometric enzyme immunoassay for myoglobin (Myo) for early diagnosis of acute myocardial infarction (AMI) in patients in the emergency department. The rapid fluorometric enzyme immunoassay for myoglobin was performed on timed blood samples collected previously for serial CK and CKMB determinations from 41 patients who initially presented to the ED with chest pain and were subsequently admitted to patient care units. Twenty two patients were AMI positive and 19 were AMI negative. In 12 patients who were AMI positive, Myo increased rapidly and significantly peaking at 6.53 +/- 5.45 hours, whereas in the other 10 patients who were AMI positive, only the declining slopes of Myo were observed due to late AMI presentation. In the AMI negative group, Myo values were within reference range in 8 and persistently elevated in 11. Using the initial rate of Myo release of 20 ng/mL per hour as criteria of discrimination, this assay has a sensitivity of 90.1% and a specificity of 74%. Available samples for the two patients who were false negative were past the window of Myo release for AMI detection. All five patients who were false positive were associated with various degrees of muscular trauma or renal disorder. The authors conclude that the initial rate of Myo release demonstrates good utility both at early detection and early exclusion of AMI. However, its tissue nonspecificity may not permit AMI recognition in the presence of muscular injury. PMID- 7785658 TI - Acute intermittent porphyria in a native North American family. Biochemical and molecular analysis. AB - A native North American family with acute intermittent porphyria was investigated by molecular methods to locate the causative mutation and identify carriers of the mutant allele. All 15 exons of the porphobilinogen deaminase gene were screened by single-strand conformation polymorphism analysis, and a unique banding pattern was observed in exon 14. Sequencing revealed a one base-pair insertion in this exon that shifts the reading frame of the mRNA, and generates a premature stop codon. Family members were tested for the mutation by amplification of exon 14 followed by digestion with the restriction enzyme NlaIII. The activity of erythrocyte porphobilinogen deaminase was measured in 36 family members. The results agreed with mutational analysis in 32 cases. However, four individuals who were not gene carriers had low enzyme activity, and in the absence of molecular genetic data would have been incorrectly diagnosed. This is the first study to identify the molecular basis of acute intermittent porphyria in native North Americans. PMID- 7785659 TI - Heparin-induced increase in the international normalized ratio. Responses of 10 commercial thromboplastin reagents. AB - A clinician's concern about an erratic response to oral anticoagulation in a patient treated concurrently with heparin and warfarin led the authors to investigate the effect of heparin on INR values obtained with various commercial thromboplastin reagents. Studies conducted with pooled normal plasma and with pooled plasma from patients treated long-term with oral anticoagulants demonstrated a wide range of sensitivities to heparin of these reagents as characterized by prolongation of INR values. Innovin was unaffected by concentrations of heparin as high as 1 U/mL. In contrast, Ortho thromboplastin showed the greatest increase in INR values over the range of heparin concentrations studied. Three other thromboplastins including Neoplastine CI, Dade thromboplastin, and Simplastin A demonstrated only limited sensitivity to heparin. Prolongation of the INR by heparin was reversed by protamine in a dose related manner and also by preincubation of the plasma with heparinase. Some patients treated with warfarin while on the authors' institutional protocol for heparin had plasma concentrations greater than 0.8 U/mL. When thromboplastin reagents sensitive to heparin were used with such specimens, the INR values obtained were falsely elevated. The authors suggest that reagents insensitive to heparin be employed to avoid this difficulty. PMID- 7785660 TI - Platelet satellitism is Fc gamma RIII (CD16) receptor-mediated. AB - Platelet satellitism (PS), the phenomenon of platelet rosetting around polymorphonuclear neutrophils (PMN), which is observed in ethylenediamineetetraacetic acid (EDTA)-anticoagulated blood at room temperature, is caused by the presence of IgG autoantibodies in the serum. Fourteen patients with PS were studied, and the presence of both EDTA-dependent antiplatelet and EDTA-dependent antineutrophil IgG (auto)antibodies were found in their sera. Anti neutrophil activity was completely abolished when the sera were absorbed on normal platelets, which suggests that a single antibody is involved. Inhibition studies with monoclonal antibodies indicated that this IgG autoantibody is directed against the glycoprotein IIb/IIIa complex of the platelet membrane, as well as the neutrophil Fc gamma receptor III (Fc gamma RIII). In addition, the antibody did not react with platelets from a patient with type I Glanzmann's disease, nor with neutrophils from a patient with congenital Fc gamma RIII absence (NAnull phenotype), thus confirming both specificities. As in other literature cases, a clear correlation between the presence of this IgG and a specific clinical situation, disease, or use of drugs could not be shown. Therefore, these antibodies, which are present in some normal individuals, might occur naturally. Because of the exposure of particular cryptoantigenic structures present on EDTA-modified platelet and PMNs, they may manifest themselves by triggering the PS phenomenon. PMID- 7785661 TI - The effect of a heparin removal filter on platelet aggregation studies in heparin induced thrombocytopenia. AB - Patients having a heparin-associated platelet antibody who are receiving heparin at the time of testing for heparin-induced thrombocytopenia (HIT) by platelet aggregometry may exhibit aggregation in the negative control channel. Filtering plasma to remove the heparin in may produce a nonaggregating negative control channel. The effect of the Pall Hepchek (Pall Biomedical, East Hills, NY) heparin removal filter on platelet aggregation studies was evaluated. Samples were studied from 10 patients with clinically established HIT. The pre-filtration platelet aggregation studies were unequivocally positive for heparin antibody. The remainder of each sample was filtered and the aggregation studies were repeated. Of the four patients on IV heparin, only one remained positive post filtration. Of the six patients receiving subcutaneous heparin or flushes, one remained strongly positive, one was borderline, and four became negative. Pall Hepchek heparin filtration unpredictably alters the results of platelet aggregation studies, and should not be used routinely to remove heparin in the presence of aggregation in the negative control. PMID- 7785663 TI - Lymphocytosis of gamma/delta T cells in human ehrlichiosis. AB - The majority of T cells in peripheral blood express a T-cell receptor (TCR) comprised of alpha and beta chains. An alternate form of the TCR is comprised of gamma and delta chains. These gamma/delta T cells are associated with certain infectious lesions, and modestly elevated in peripheral blood in certain disease states. Human ehrlichiosis is characterized by hematologic abnormalities including multi-lineage cytopenias. In most cases reported, a lymphocytopenia has been present either at diagnosis, or at some time during the illness. Early in the course of antibiotic treatment (48-72 hours), the lymphocytopenia corrects itself and is rapidly followed by a lymphocytosis of T cells that express CD3, but are negative for CD4 and CD8, as well as the major form of the TCR formed by the alpha/beta heterodimer. Instead, these CD3+4-8- T cells express the gamma/delta heterodimer associated with V gamma 9 and V delta 2 chains, a population of cells usually the distinctive minority of peripheral blood T cells, but constituting the major phenotype of peripheral gamma/delta T cells. PMID- 7785662 TI - Posttransplantation lymphoproliferative disorders in solid organ recipients are predominantly aggressive tumors of host origin. AB - Patients immunosuppressed after organ transplantation have an increased frequency of lymphoproliferative disorders, known as posttransplantation lymphoproliferative disorders (PTLDs). In recipients of bone marrow allografts. PTLDs are often of donor origin. In only a few cases of lymphoma arising in solid organ transplant recipients has the origin from host or donor lymphocytes been established. The authors have analyzed 11 cases of PTLD from Massachusetts General Hospital, arising in seven male and four female patients, aged 8 to 63, five with renal, four with cardiac, and two with hepatic allografts. Using the polymerase chain reaction (PCR) to investigate genetic polymorphism at the D4S174 locus on chromosome 4, the Rb1.20 locus on chromosome 13, and the D19S178 locus on chromosome 19, only one tumor (previously reported) was of donor origin, whereas 10 were of host origin. Follow-up revealed that six patients died of PTLD, one was alive with recurrent PTLD, and four were alive and well or had died of other causes, including the patient with donor-origin PTLD. Based on these cases and on a review of previously reported cases, the authors conclude that the majority of PTLDs in solid organ recipients are of host origin. There appears to be a trend toward a greater likelihood of persistent or recurrent PTLD among solid organ recipients with host-origin tumors than among those with donor-origin tumor. PMID- 7785664 TI - Comparing methods of estimating maximum allowable analytical error in glycohemoglobin testing. PMID- 7785665 TI - S100 protein and HMB-45 negative "rhabdoid" malignant melanoma: a totally dedifferentiated malignant melanoma? PMID- 7785666 TI - Invited commentary on "Aerial dissemination of pulmonary tuberculosis. A two-year study of contagion in a tuberculosis ward". PMID- 7785667 TI - Re: "Validity of parental report of a child's medical history in otitis media research". PMID- 7785668 TI - Re: "Statistical significance testing in the American Journal of Epidemiology, 1970-1990". PMID- 7785669 TI - Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases. AB - The association of daily cardiac and respiratory admissions to 168 acute care hospitals in Ontario, Canada, with daily levels of particulate sulfates was examined over the 6-year period 1983-1988. Sulfate levels were recorded at nine monitoring stations in regions of southern and central Ontario spanned by three monitoring networks. A 13-micrograms/m3 increase in sulfates recorded on the day prior to admission (the 95th percentile) was associated with a 3.7% (p < 0.0001) increase in respiratory admissions and a 2.8% (p < 0.0001) increase in cardiac admissions. Increases were observed for all age groups examined. Admissions for cardiac diseases increased 2.5% for those under 65 years and 3.5% for those 65 years and older. After adjusting for ambient temperature and ozone, similar increases in respiratory admissions were observed in the period from April to September (3.2%) and in the period from October to March (2.8%). A 3.2% increase was observed for cardiac admissions in the period from April to September, and a 3.4% increase was observed in the period from October to March after adjusting for ambient temperature and ozone. PMID- 7785670 TI - Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. AB - In the December 1952 smog disaster in London, a substantial increase in mortality was closely associated with the increase in air pollution. Deaths from cardiovascular causes were elevated as well as respiratory deaths. The increase was greatest in the elderly. Hospital admissions were increased for both respiratory and cardiovascular diseases. Since then, many studies have reported associations between lower concentrations of air pollution and daily mortality. Little attention has been paid to the question of hospital admissions for cardiovascular illness, however. This study examined the association between air pollution and cardiovascular hospital admissions for persons aged 65 years and older in the Detroit, Michigan, metropolitan area during the years 1986-1989. After controlling for seasonal and other long-term temporal trends, temperature, and dew point temperature, the particulate matter with an aerodiameter of < or = 10 microns (PM10) was associated with daily admissions for ischemic heart disease (relative risk (RR) = 1.018, 95% confidence interval (CI) 1.005-1.032 for an interquartile range (32 micrograms/m3) increase in pollution). SO2, CO, and ozone made no independent contribution to ischemic heart disease admissions. Both PM10 (RR = 1.024, 95% CI 1.004-1.044) and CO (RR = 1.022, 95% CI 1.010-1.034 for an interquartile range (1.28 ppm) increase in pollution) showed independent associations with heart failure admissions. These results were robust to alternate methods of estimation and weather control. PMID- 7785671 TI - Aerial dissemination of pulmonary tuberculosis. A two-year study of contagion in a tuberculosis ward. 1959. PMID- 7785672 TI - Clustering of risk habits in young adults. The Cardiovascular Risk in Young Finns Study. AB - The authors studied the occurrence of common lifestyle risk factors, namely, nonprudent diet, smoking, physical inactivity, and frequent inebriation by alcohol in a cohort of young adults aged 18, 21, and 24 years (n = 484) as part of the Cardiovascular Risk in Young Finns Study in 1986. Risk habits showed significant clustering; the number of subjects was greater than expected in groups with zero and three of four risk habits and less than expected in the group with only one or two risk habits. Stepwise logistic regression analysis was used to find independent determinants for this clustering from a set of socioeconomic, demographic, and behavioral (type A components) determinants. The logistic model suggested several independent risk factors for risk habit clustering. These included male sex, aggressiveness, and past unemployment. Paying a lot of attention to health habits, higher education (being a student), good self-perceived health, and a high sense of responsibility seemed to be protective factors against risk habit clustering. The accumulation of risk habits was also associated with an atherogenic lipid and blood pressure profile (clustering of high density lipoprotein cholesterol/total cholesterol ratio, triglycerides, and diastolic blood pressure in their extreme tertiles). These findings show that common risk habits cluster among young adults. Knowledge about the determinants of this clustering will aid in the planning of future preventive strategies against cardiovascular diseases in young people. PMID- 7785673 TI - Coronary heart disease mortality and sudden death: trends and patterns in 35- to 44-year-old white males, 1970-1990. AB - Trends in coronary heart disease mortality and sudden death were studied in 35- to 44-year-old white male residents of Allegheny County, Pennsylvania. Deaths coded as any cardiac or vascular disease, diabetes, unexplained sudden death, and other rubrics were eligible for investigation, and the cause of death was validated by physicians examining multiple data sources about the deaths. During 1970-1990, 1,424 white male deaths were investigated, with 903 validated as coronary heart disease. In that time span, white male coronary heart disease mortality fell from 93.4 to 36.7 per 100,000 population per year, a 60% decline. Little proportionate change was seen in characteristics of the deaths, which were predominantly sudden and out-of-hospital. Diabetes mellitus history increased proportionately over time, largely because diabetics' mortality rates, unlike those of all other subgroups, did not fall. These observations support the contention that the decline in coronary heart disease mortality relates to risk factor modification more than to improvements in the treatment of coronary heart disease. Differences in death certification practices must be considered when interpreting and comparing vital statistics data. PMID- 7785674 TI - Relation of body fat distribution to ischemic heart disease. The National Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study. AB - Although an excess of adipose tissue in the abdominal and truncal regions is associated with various metabolic alterations, relatively few cohort studies have examined its importance in the development of ischemic heart disease, and little information is available from black populations. The authors examined the relation of central obesity, as characterized by a thick subscapular skinfold relative to the triceps skinfold, to the incidence of ischemic heart disease among 9,822 persons in the Epidemiologic Follow-up Study of the National Health and Nutrition Examination Survey I; baseline data were collected in 1971-1975 and follow-up was through 1987. We found that, independently of relative weight, cigarette smoking, and other covariates, the hazard rate ratios for ischemic heart disease incidence contrasting the upper and lower quintiles of central obesity were 1.75 (95% confidence interval 1.3-2.3) among women and 1.65 (95% confidence interval 1.3-2.2) among men. Although central obesity was related similarly to disease among white and black men, the association among women differed between whites (rate ratio = 1.94) and blacks (rate ratio = 0.73); p = 0.002 for race x the central obesity product term. Additional research is needed to clarify the relation of various anthropometric measurements to ischemic heart disease, particularly among blacks, but the assessment of fat distribution may help identify high-risk persons for whom weight loss might be most beneficial. PMID- 7785675 TI - Effects of question order on estimates of the prevalence of attempted weight loss. AB - Although numerous surveys have been conducted to estimate the prevalence of attempted weight loss, little information is available on the possible effects of question order on the prevalence estimates. The authors examined data collected from 231,852 respondents to surveys conducted in the District of Columbia and 20 states that participated in the Behavioral Risk Factor Surveillance System between 1985 and 1992. In surveys conducted from 1985 to 1988, respondents (n = 117,827) were first asked their body weight and then were asked if they were trying to lose weight; 48% of the women and 29% of the men reported that they were trying to lose weight. In 1989, 1991, and 1992 (no questions about weight control were asked in 1990), the order of the questions was reversed so that respondents (n = 114,025) were asked whether they were trying to lose weight before they were asked to report their weight; 41% of the women and 26% of the men reported that they were trying to lose weight. The authors conclude that survey respondents, especially women, may be more likely to report that they are trying to lose weight when questions about weight control practices immediately follow questions on current weight. This apparent effect of question order points to the need for caution in comparing prevalence estimates across surveys in which the questions are not asked in a similar order, even when the questions are worded identically. PMID- 7785676 TI - Incidence of benign gastrointestinal tumors among atomic bomb survivors. AB - Using the Hiroshima and Nagasaki tumor and tissue registries, benign tumors of the stomach, colon, and rectum were identified among members of the Life Span Study cohort of atomic bomb survivors. During the period 1958-1989, a total of 470 cases with histologically confirmed benign gastrointestinal tumors (163 stomach, 215 colon, and 92 rectum) were identified among approximately 80,000 Life Span Study members with known radiation doses, who were alive in 1958. Restricting the analysis to adenomatous tumors not detected at autopsy, a dose response relation was observed for stomach tumors (excess relative risk at 1 sievert (ERR1Sv) = 0.53; 95% confidence interval (CI) -0.01 to 1.43). However, there was little evidence of a dose response for colon tumors (ERR1Sv = 0.14; 95% CI -0.20 to 0.76), and no evidence was present for rectal tumors (ERR1Sv = -0.25; 95% CI undetermined to 0.80). The excess relative risk (ERR) for benign tumors of the stomach is consistent with the excess found for stomach cancer. For cancer of the rectum, the dose response was not significant, but the point estimate of the excess relative risk was positive. The excess relative risk for benign colon tumors is less than that reported for colon cancer (ERR1Sv = 0.72). The authors observed a dramatic increase in colon tumors detected after 1985, suggesting that the relatively recent introduction of colonoscopy may be influencing these results. PMID- 7785677 TI - Irritable bowel syndrome in a community: symptom subgroups, risk factors, and health care utilization. AB - The clinical relevance of subdividing the irritable bowel syndrome (IBS) into subgroups based on bowel habit is largely unknown. We therefore obtained an age- and sex-stratified random sample of Olmsted County, Minnesota, residents aged 20 95 years. All subjects were mailed a valid self-report questionnaire during the years 1988-1993; the response rate was 74% (n = 3,022). Among subjects with IBS (n = 536), four symptom-based subgroups of similar size were identified: constipation predominant, diarrhea predominant, alternating constipation and diarrhea, and neither. The prevalence of IBS was significantly greater in females, primarily because of a higher prevalence of constipation-predominant IBS in women. Of persons > or = 60 years of age, 23% reported the initial onset of IBS in the previous year compared with 10% in younger subjects; the age at onset of IBS was similar among the subgroups. Marital status, education level, smoking, and alcohol use were not significantly different among the subgroups. Of those with IBS, 25% reported visiting a physician for abdominal pain or disturbed defecation in the prior year compared with only 8% of persons without IBS. Female sex, an increased number of Manning's symptom criteria, and the individual IBS subgroups were not associated with higher rates of physician visits. We conclude that the onset of IBS may not be limited to early adulthood and that subgroups of IBS based on bowel patterns may not identify clinically distinct entities. PMID- 7785678 TI - Fetal growth retardation in sudden infant death syndrome (SIDS) babies and their siblings. AB - To evaluate the intrauterine growth potential of infants that die from sudden infant death syndrome (SIDS), the authors compared SIDS infants with their surviving siblings. The SIDS sibships themselves were also compared with sibships where all infants survived. Data from the population-based Medical Birth Registry of Norway, with 1.3 million births during 1967-1988, were used. From the birth cohorts, 1,984 SIDS cases were identified. All births were linked into sibships. The mean birth weight and gestational age were calculated across sibships of different sizes for first to fourth birth order. In a further analysis, birth weights were standardized to adjust for gestational age. Mothers of SIDS infants give birth to smaller babies in general. SIDS infants weighed, on average, 85 g less at birth than their siblings and 164 g less compared with babies in nonaffected sibships. When birth weights were standardized for gestational age, most of the weight difference between SIDS infants and siblings was due to a shorter gestational age of SIDS infants, while the difference between surviving siblings of SIDS infants and births from nonaffected sibships remained. All births in sibships with a SIDS infant were intrauterine growth retarded. This may reflect factors that contribute to SIDS risk (such as maternal smoking). The factors that contribute to shorter gestational age and further slowing of growth in the SIDS infants may specifically influence the SIDS infant and not its siblings. PMID- 7785679 TI - Control sampling strategies for case-crossover studies: an assessment of relative efficiency. AB - The case-crossover study design is a method to assess the effect of transient exposures on the risk of onset of acute events. Control information for each case is based on his/her past exposure experience, and a self-matched analysis is conducted. Empiric evaluation of five approaches to the analysis of case crossover data from a study of heavy physical exertion and acute myocardial infarction onset is shown. The data presented are from the Onset Study, a case crossover study of the determinants of myocardial infarction onset conducted in 45 centers from August 1989 to October 1992. In model 1, exactly one control period (matched on clock-time) was sampled per case. In models 2-4, up to 25 control periods were sampled, and the effect of clock-time on the baseline hazard of infarction was modeled. In model 5, a census of the person-time experienced by each subject over the year preceding the infarction was sampled. The 95% confidence interval for model 1 was 2.7 times wider, and the relative efficiency, defined as v infinity/vM, where vM represents the asymptotic variance estimate of the estimated log relative risk with M control periods sampled per case, was only about 14% of model 5. In models 2-4, the efficiency increased with the number of control periods, regardless of the modeling assumptions. Even with many control periods sampled, models 2-4 achieved only half the efficiency of model 5. The control sampling strategy in any given case-crossover study should be selected with the trade-offs between precision and potential biases of the estimates in mind. PMID- 7785680 TI - Re: "Air-conditioning and mortality in hot weather". PMID- 7785681 TI - Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma. AB - PURPOSE: We used color Doppler imaging to study blood flow velocity in the central retinal artery and the short posterior ciliary arteries in patients with glaucoma. METHOD: Fifty-two patients with chronic open-angle glaucoma, 24 patients with normal-tension glaucoma, and 28 normal subjects were studied. The mean of the peak systolic velocity, the end diastolic velocity, and the resistive index were compared in the three groups. RESULTS: Compared with the normal subjects, the patients with chronic open-angle glaucoma showed a statistically significant (P < .05) decrease in the mean end diastolic velocity and an increase in the mean resistive index in all vessels studied. The patients with normal tension glaucoma showed similar changes, achieving significance most prominently in the central retinal arteries, compared with normal subjects (P < .05). There were no statistically significant differences between the patients with chronic open-angle glaucoma and those with normal-tension glaucoma. CONCLUSIONS: Open angle glaucoma appears to be associated with a decreased mean flow velocity and an increased mean resistive index in the ocular vasculature. These changes are in keeping with possibly compromised circulation in this region. PMID- 7785684 TI - The effect of artificial tears on computer-assisted corneal topography in normal eyes and after penetrating keratoplasty. AB - PURPOSE: To examine the effect of adding artificial tears for one minute to normal eyes and eyes that have undergone keratoplasty by using computer-assisted videokeratography. METHODS: We prospectively analyzed 24 normal corneas (24 patients) chosen by random number table (reproducibility section [10 eyes], tear section [14 eyes]) as well as 14 postkeratoplasty corneas. The parametric descriptors analyzed statistically included the simulated keratometry value, surface asymmetry index, surface regularity index, power at the vertex normal, and the pupil offsets from the visual axis. Vectoral analysis was used to calculate the difference in power and axis between the simulated keratometry values before and after tear instillation. RESULTS: In normal eyes, tear instillation increased the surface asymmetry index (0.28 +/- 0.34, P = .01), changed the simulated keratometry value (0.23 diopter by 27.8 degrees), and power (0.79 +/- 0.82 diopters, P = .004) and location (0.91 +/- 0.76 mm) of the steepest point of the cornea changed. In postkeratoplasty eyes, the surface regularity index decreased (0.49 +/- 0.80, P = .04), surface asymmetry index decreased (0.37 +/- 1.03, P = .21), mean simulated keratometry value changed (1.04 diopters by 1.01 degrees), and power (0.70 +/- 2.34 diopters, P = .28) and location (1.04 +/- 1.17 mm) of the steepest point of the cornea changed. Changes were greater than the variability of the surface regularity index (0.07 +/- 0.05), surface asymmetry index (0.04 +/- 0.03), simulated keratometry value power (0.08 +/- 0.06 diopter), and axis (4.6 +/- 5 degrees). CONCLUSIONS: The addition of artificial tears to normal or regular and symmetric eyes that have undergone keratoplasty worsened symmetry and changed the power and location of the steepest point. However, the addition of artificial tears to irregular eyes that have undergone penetrating keratoplasty created a more regular and symmetric surface and significantly altered the simulated keratometry values. We recommend that corneal topography be performed before the application of artificial tears. PMID- 7785682 TI - Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker. AB - PURPOSE: To investigate the effect of topical administration of the calcium channel blocker verapamil on intraocular pressure and retrobulbar hemodynamics. METHODS: In this randomized, prospective, double-masked study, we examined the effects of single-dose topical administration of verapamil in ten normal human volunteers by using color Doppler ultrasound imaging to measure hemodynamic parameters. Limitations of this study include single-dose application of verapamil and relatively small sample size. RESULTS: No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The intraocular pressure significantly decreased compared with baseline two hours after topical 0.125% and 0.25% verapamil (P = .015 and .040, respectively). Pourcelot's ratio, an index of vascular resistance, measured in the central retinal artery was significantly reduced after topical application of 0.125% verapamil (P = .008). The change in Pourcelot's ratio primarily resulted from an increased end diastolic velocity in the central retinal artery. No significant differences compared with baseline values were detected in the color Doppler ultrasound measurements of the posterior ciliary arteries and the central retinal vein two hours after topically administered verapamil. CONCLUSIONS: Topical administration of verapamil decreases intraocular pressure and alters ocular hemodynamics, reducing the vascular resistance index in the central retinal artery. PMID- 7785683 TI - Membranous outgrowth suggesting lens epithelial cell proliferation in pseudophakic eyes. AB - PURPOSE: We sought to determine the incidence and structure of membranous outgrowth, which extends from the anterior capsular opening onto the intraocular lens surface in pseudophakic eyes. METHODS: Thirty-four eyes of 31 patients with age-related cataract were prospectively studied. No patient had any abnormality other than cataract. Each patient underwent continuous circular capsulorhexis, phacoemulsification, and implantation within the capsule of a three-piece posterior chamber lens. A slit lamp and specular microscope were used to observe and photograph the intraocular lens surface and anterior capsular opening every day for the first postoperative week, and at days 14, 21, and 28. We counted the number of eyes with the membranous outgrowth and graded the outgrowth according to its shape and length at each postoperative period. RESULTS: In total, 27 of 34 (79%) eyes had the membranous outgrowth from the anterior capsular opening onto the intraocular lens surface. The membrane was first observed on day 3. Three of 34 eyes had the dendritic or fan-shaped structure, which extended less than 0.5 mm from the capsular edge. The membranes were most frequently found on day 7. Twenty-five of 34 eyes had the outgrowth in various grades. After four weeks, no membranes were observed. CONCLUSIONS: The time course and structure of the membranous outgrowth we observed were comparable to those of the outgrowth of lens epithelial cells under tissue culture conditions. The membranous outgrowth may be the result of a transient but active proliferation of human lens epithelial cells onto the intraocular lens surface. PMID- 7785685 TI - Assessment of the power and height of radial aspheres reported by a computer assisted keratoscope. AB - PURPOSE: The two purposes of this study were (a) to assess the accuracy with which a keratoscope, the Topographic Modeling System (TMS-1), calculated the heights and powers of rotationally symmetric, radially aspheric test surfaces and (b) to determine whether the TMS-1 used an axial solution for radius of curvature to determine the power of a sphere that would produce the same semichord as would the test surface on a keratograph. METHODS: The TMS-1 heights and powers were studied for four test surfaces that had radial profiles similar to those of normal corneas. The powers of the surfaces were calculated from the local radius of curvature derived from the surfaces' manufacturing formulas. The heights and powers that would result from an axial solution were calculated in a TMS-1 simulator. TMS-1 data were compared with data from the surfaces' formulas and with data from the simulation. RESULTS: The TMS-1 data were almost identical to the heights and powers calculated from the simulated axial solution. The TMS-1 data were similar to the heights and powers calculated from the mathematical formulas from the apex to 2 mm from the apex but differed by up to 85 microns of height and 10 diopters of power in the periphery. CONCLUSIONS: The TMS-1 appeared to use the axial solution that does not calculate power from local radius of curvature. Clinicians should use caution when inferring corneal shape from power maps based on an axial solution, especially outside the central 2-mm radius of a normal cornea, because such power does not depict corneal curvature. PMID- 7785686 TI - Refractive changes at extreme altitude after radial keratotomy. AB - PURPOSE: We studied the effects of altitude on four corneas that had undergone radial keratotomy and four normal corneas exposed to increasing elevation during a high-altitude excursion. METHODS: We measured visual acuity, cycloplegic refraction, keratometry, and intraocular pressure at sea level and after 24-hour exposure to 12,000 and 17,000 ft. RESULTS: We observed a significant increase in spherical equivalence (hyperopic shift) in radial keratotomy eyes exposed to altitude as compared to controls (P < .0001). The average change in spherical equivalent cycloplegic refraction from sea level to 12,000 ft was 1.03 +/- 0.16 diopters and from sea level to 17,000 ft was 1.94 +/- 0.26 diopters. We also observed a significant decrease in keratometry values at altitude as compared with control corneas (P < .0001). The average change in keratometry from sea level to 12,000 ft was 0.59 +/- 0.19 diopter and from sea level to 17,000 ft was 1.75 +/- 0.27 diopters. CONCLUSIONS: Although the specific origin of these changes is open to question, we hypothesize that hypoxic corneal expansion in the area of the radial keratotomy incisions may lead to central corneal flattening and a hyperopic shift in refractive error. The cornea that has undergone radial keratotomy appears to adjust constantly to changing environmental oxygen concentration, producing a new refractive error over a period of 24 hours or more. Additional study is required to identify with certainty the specific origin of the hyperopic shift at high altitude. PMID- 7785687 TI - The effect of cleaning and disinfection of soft contact lenses on corneal infectivity in an animal model. AB - PURPOSE: Bacterial contamination of previously worn soft contact lenses, especially at sites of lens deposits, might play a role in the pathogenesis of lens-associated bacterial keratitis. We studied the effects of three commercial contact lens cleaners and disinfectants in a rabbit model to determine whether cleaning and disinfection reduced infectivity. METHODS: Duragel 75 soft contact lenses, designed to fit the eyes of rabbits, were worn by rabbits under tarsorrhaphies, then were removed and cleaned in one of three cleaner and disinfectant solutions according to the manufacturers' instructions. The lenses were contaminated by overnight incubation in a suspension of 10(8) Pseudomonas aeruginosa/ml and were placed under tarsorrhaphies on the eyes of fresh rabbits. The rabbits were observed for two weeks for signs of infection. Control rabbits wore new, uncleaned but contaminated lenses or worn, uncleaned but contaminated lenses. RESULTS: The rates of infection with the three commercial cleaner and disinfectant solutions ranged from 18% (two of 11) to 31% (four of 13); these incidences were not significantly different from one another or from the 19% (three of 16) incidence with new, contaminated but uncleaned lenses. By contrast, when worn, uncleaned but contaminated lenses were placed in rabbits' eyes, seven of eight were infected, a rate that is significantly higher than that of the other four groups (P = .0003). CONCLUSIONS: These data indicate that the three commercial lens cleaner and disinfectant solutions were of similar efficacy in reducing the infectivity of contaminated contact lenses to a level similar to that of new, unworn lenses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785688 TI - The prevalence of dissociated vertical deviation in patients with sensory heterotropia. AB - PURPOSE: We reviewed 281 consecutive patients with sensory esotropia or exotropia to determine the prevalence of dissociated vertical deviation in patients with sensory strabismus. METHODS: We reviewed the charts of all patients who received a diagnosis of sensory heterotropia or dissociated vertical deviation and who were examined at the Pediatric Ophthalmology Service at the Texas Children's Hospital between 1973 and 1992. Statistical analyses of the prevalence of dissociated vertical deviation were determined after evaluating the direction of the accompanying horizontal strabismus and examining the temporal relationship of the unilateral vision loss. RESULTS: Dissociated vertical deviation was diagnosed in 35 patients (12.5%). It occurred more frequently in sensory esotropia (22 patients, 18.3%) than exotropia (13 patients, 8.1%) (P = .009). The age at which unilateral visual loss occurred did not influence the development of dissociated vertical deviation. CONCLUSION: Dissociated vertical deviation in patients with acquired loss of vision does not support the contention that dissociated vertical deviation is a genetically predetermined anomaly of binocular vision. PMID- 7785690 TI - Reappraisal of biomicroscopic classification of stages of development of a macular hole. AB - PURPOSE: To update the biomicroscopic classification and anatomic interpretations of the stages of development of age-related macular hole and provide explanations for the remarkable recovery of visual acuity that occurs in some patients after vitreous surgery. METHODS: Recent biomicroscopic observations of various stages of macular holes are used to postulate new anatomic explanations for these stages. RESULTS: Biomicroscopic observations include the following: (1) the change from a yellow spot (stage 1-A) to a yellow ring (stage 1-B) during the early stages of foveal detachment is unique to patients at risk of macular hole; (2) the prehole opacity with a small stage 2 hole may be larger than the hole diameter; and (3) the opacity resembling an operculum that accompanies macular holes is indistinguishable from a pseudo-operculum found in otherwise normal fellow eyes. CONCLUSIONS: The change from a yellow spot (stage 1-A) to a yellow ring (stage 1-B) is caused primarily by centrifugal displacement of retinal receptors after a dehiscence at the umbo. The hole may be hidden by semiopaque contracted prefoveolar vitreous cortex bridging the yellow ring (stage 1-B occult hole). Stage 1-B occult holes become manifest (stage 2 holes) either after early separation of the contracted prefoveolar vitreous cortex from the retina surrounding a small hole or as an eccentric can-opener-like tear in the contracted prefoveolar vitreous cortex, at the edge of larger stage 2 holes. Most prehole opacities probably contain no retinal receptors (pseudo-opercula). Surgical reattachment of the retina surrounding the hole and centripetal movement of the foveolar retina induced by gliosis may restore foveal anatomy and function to near normal. PMID- 7785689 TI - Diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis. AB - PURPOSE: To determine possible side effects of diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis. METHODS: In a prospective clinical study, threshold retinopathy of prematurity was treated in 14 eyes of seven consecutive preterm infants with tunica vasculosa lentis (birth weight, 480 to 980 g; mean +/- S.D., 777 +/- 175 g; gestational age, 24 to 27 weeks; mean +/- S.D., 25.7 +/- 0.9 weeks) by using the diode laser indirect ophthalmoscope. Main outcome measure was the incidence of adverse treatment effects. Follow-up included anterior segment examination with a hand held slit lamp and ranged from seven to 17 months (12.6 +/- 3.5 months). RESULTS: The tunica vasculosa lentis did not interfere with photocoagulation in any of the 14 eyes. Laser power ranged from 200 to 400 mW (260 +/- 52 mW). Duration of a single spot was 200 msec. Number of burns ranged from 1,060 to 2,132 (1,556 +/- 315). Retinopathy of prematurity regressed in all eyes, and the outcome was a flat, attached retina. A small amount of postoperative anterior chamber bleeding was noticed in one eye (7% of the eyes, 14% of the patients). There were neither lenticular opacities nor cataract formation. CONCLUSION: Diode laser photocoagulation with the laser indirect ophthalmoscope can be used safely in eyes with tunica vasculosa lentis. At the laser energy levels used in our study, no transient lens opacities or cataract formation occurred. However, the results of this study are limited by a relatively small number of patients and a relatively short follow-up. PMID- 7785691 TI - Quantitation of retinal ablation in proliferative diabetic retinopathy. AB - PURPOSE: We studied 294 eyes of 182 patients, to quantitate the amount of retinal ablation required for regression of proliferative diabetic retinopathy. METHODS: Eyes included in the study had two or more proliferative diabetic retinopathy risk factors, received panretinal photocoagulation, and had a minimum follow-up of one year. Laser photocoagulation or cryotherapy was given to eyes that failed to regress or had progression of retinopathy. Eyes treated by other physicians, treated with xenon arc photocoagulation, or undergoing laser treatment or vitrectomy for other retinal conditions were excluded. The total area of retina ablated was calculated and used as a quantitative measure of treatment. RESULTS: Regression was observed in 275 eyes (93%); 19 eyes (7%) failed to regress and eventually required vitrectomy. Panretinal photocoagulation alone successfully led to regression in 229 eyes (77%), whereas 46 eyes (15.6%) required both photocoagulation and peripheral anterior retinal cryotherapy. An average of 1.7 treatments per eye led to regression. Eyes were bimodally distributed by requirement for treatment, into low and high treatment groups. Low treatment eyes received an average of 510 mm2 of retinal ablation (2,600 500-microns burns), and high treatment eyes, 1,280 mm2 (6,500 500-microns burns). More extensive treatment was required with more retinopathy risk factors (P = .002 for four vs three risk factors and P = .0007 for four vs two risk factors); duration of diabetes mellitus longer than 15 years (P = .004), and onset of diabetes mellitus before 30 years of age (P = .0008). CONCLUSION: Patients with proliferative diabetic retinopathy should be treated aggressively with panretinal photocoagulation, cryotherapy, or both. The amount of initial treatment required for regression may be considerably more than that recommended by the Diabetic Retinopathy Study. PMID- 7785692 TI - Accidental Nd:YAG laser injuries to the macula. AB - PURPOSE: To study the clinical course of accidental, single-focus Nd:YAG laser injuries to the macula. METHODS: We reviewed the clinical course of five eyes (four patients) that sustained macular injuries from a Nd:YAG laser. All patients were examined within 24 hours of injury and were observed without surgical intervention for a mean of 20 months (range, 12 to 32 months). RESULTS: A single full-thickness foveal or parafoveal retinal hole was apparent in all eyes either on initial examination or within two weeks of injury. All macular holes were within 650 microns of the foveal center. The mean final visual acuity was 20/60 (range, 20/25 to 20/400) and was related to the distance between the macular hole and the foveal center. None of the eyes developed either subretinal neovascularization or clinically significant epiretinal membrane formation during the study period. CONCLUSIONS: Despite initial poor visual acuity in patients who had a full-thickness foveal or parafoveal retinal hole, visual acuity improved without treatment when the site of the laser injury was located outside the foveal center. PMID- 7785693 TI - Vancomycin levels in the vitreous cavity after intravenous administration. AB - PURPOSE: We studied the effects of inflammation, repeated antibiotic doses, and the surgical status of the eye on penetration of vancomycin hydrochloride into the rabbit vitreous cavity after intravenous administration. METHODS: We studied three anatomic states (phakic, aphakic, and aphakic, vitrectomy-treated eyes) subdividing each into inflamed and noninflamed groups. Intravenous vancomycin hydrochloride (15 mg/kg of body weight) was administered every 12 hours for 48 hours. Eyes were harvested for the assay of vitreous cavity antibiotic levels at various intervals from one to 49 hours. We determined concentrations and calculated mean values and S.E.M. RESULTS: Therapeutic levels were not established in the vitreous cavity at any time period in the two phakic groups. At 25 hours, the inflamed aphakic eyes had concentrations of 5.05 +/- 1.9 micrograms/ml and the control noninflamed aphakic eyes 4.5 +/- 1.23 micrograms/ml; slight increases were found by 49 hours. Concentrations tested in the aphakic, vitrectomy-treated eyes at two, 13, 25, and 49 hours demonstrated progressive increases both in the inflamed eyes (5.4 +/- 2.4 micrograms/ml, 9.64 +/- 4.25 micrograms/ml, 9.2 +/- 3.96 micrograms/ml, 10.34 +/- 4.49 micrograms/ml) and noninflamed eyes (3.52 +/- 2.1 micrograms/ml, 5.4 +/- 1.96 micrograms/ml, 6.8 +/- 2.53 micrograms/ml, 8.7 +/- 5.44 micrograms/ml). CONCLUSIONS: Vitreous vancomycin concentrations in aphakic and aphakic, vitrectomy-treated eyes after intravenous administration exceed the minimal inhibitory concentrations for the usual gram-positive pathogens that create endophthalmitis, suggesting a role for intravenous vancomycin in the treatment of bacterial endophthalmitis. PMID- 7785694 TI - Metastatic tumors to the pituitary. AB - PURPOSE: To illustrate how the ophthalmologist can distinguish a metastatic tumor to the pituitary from a pituitary adenoma through clinical, particularly ophthalmic, findings. METHODS: We studied three patients with metastatic disease to the pituitary. One patient had a history of breast cancer without known metastatic disease, and two patients had no previous diagnosis of malignancy. We reviewed the literature with respect to signs and symptoms that may differentiate such lesions from histologically benign pituitary adenomas. RESULTS: Including our patients and the recent cases in the literature, 42% of patients with metastatic tumors had oculomotor palsies, compared with less than 5% of patients with pituitary adenomas. Of patients with metastatic tumors, 33% had diabetes insipidus, compared with 1% who had pituitary adenomas. Furthermore, with respect to differentiating a pituitary adenoma from a metastatic process, radiographic examinations were not helpful, and histopathologic examination was occasionally incorrect. CONCLUSION: The ophthalmologist can potentially differentiate a metastatic tumor to the pituitary from a pituitary adenoma, thereby assisting in the proper treatment of patients. PMID- 7785695 TI - No demonstrated effect of pre-enucleation irradiation on survival of patients with uveal melanoma. AB - PURPOSE: To evaluate the hypothetical effect of pre-enucleation irradiation on survival of patients with uveal melanoma. METHODS: In a prospective study between 1978 and 1990, 145 patients with uveal melanoma were treated by irradiation in two fractions of 4 Gy before enucleation. A historical control group of 89 patients with uveal melanoma treated by enucleation alone was operated on between 1971 and 1990. Patients were followed up until December 1992 or until death. The mean follow-up period was 65 months in the irradiated group and 88 months in the control group. RESULTS: The preoperatively irradiated group of patients showed no significant improvement of the survival rate after 7 1/2 years (75.9%) compared with the control group (72.1%). Preoperative irradiation was not associated with survival (P = .93), as assessed by Cox proportional hazard analysis, adjusted for age, gender, tumor location, tumor size, cell type, and year of enucleation. Women in both the irradiated and control groups had a better prognosis than men (P = .002). CONCLUSION: Preoperative irradiation in this nonrandomized study had no effect on survival of patients with uveal melanoma. PMID- 7785696 TI - Diagnostic criteria for Graves' ophthalmopathy. AB - PURPOSE: To propose criteria for the diagnosis of Graves' ophthalmopathy. METHODS: We reviewed the evolution of nomenclature describing Graves' ophthalmopathy. and the diagnostic schema used in key published reports. RESULTS: A laboratory test or clinical finding pathognomonic for Graves' ophthalmopathy currently is not available or recognized. Extant diagnostic criteria may exclude appropriate cases. CONCLUSIONS: Graves' ophthalmopathy is considered to be present if eyelid retraction occurs in association with objective evidence of thyroid dysfunction or abnormal regulation, exophthalmos, optic nerve dysfunction, or extraocular muscle involvement. The ophthalmic signs may be unilateral or bilateral, and confounding causes must be excluded. If eyelid retraction is absent, then Graves' ophthalmopathy may be diagnosed only if exophthalmos, optic nerve involvement, or restrictive extraocular myopathy is associated with thyroid dysfunction or abnormal regulation and if no other cause for the ophthalmic feature is apparent. PMID- 7785697 TI - Possible role of herpes simplex virus in the origin of Posner-Schlossman syndrome. AB - PURPOSE/METHODS: We conducted this study to determine if the herpesviruses are possible etiologic agents in Posner-Schlossman syndrome. We aspirated aqueous humor samples from patients during acute attacks of the syndrome. Ten normal aqueous humor specimens from patients undergoing cataract surgery were used as controls. DNA was extracted and subjected to polymerase chain reaction amplification and Southern blot hybridization. RESULTS/CONCLUSION: All three specimens were positive for amplified genomic fragments of herpes simplex virus and negative for varicella-zoster virus and cytomegalovirus. Ten normal aqueous specimens were negative for all three. Herpes simplex virus may play a role in the origin of Posner-Schlossman syndrome. PMID- 7785698 TI - Infection after radial keratotomy. AB - PURPOSE/METHODS: Eight years after eight-incision radial keratotomy, a corneal ulcer developed around the inferotemporal incision in an otherwise healthy 39 year-old man. There was no history of corneal trauma or contact lens wear. RESULTS/CONCLUSIONS: Both Fusarium and Acanthamoeba organisms were eventually isolated from the ulcer. A therapeutic keratoplasty was performed. Inferotemporal incisions may be predisposed to epithelial breakdown and infection many years after radial keratotomy. PMID- 7785700 TI - Asymmetric canthaxanthin retinopathy. AB - PURPOSE/METHODS: We studied a case of crystalline retinopathy occurring after prolonged use of oral canthaxanthin. The patient was followed up for 38 months during which time she sustained a branch retinal vein occlusion in her left eye. RESULTS/CONCLUSIONS: An asymmetric appearance to the crystalline deposition was noted with increased sedimentation seen in the left eye. Vascular alterations after a branch retinal vein occlusion may lead to local stasis that may exacerbate the development of canthaxanthin retinopathy. PMID- 7785699 TI - Psoriatic corneal abscess. AB - PURPOSE/METHODS: We examined a patient with psoriasis and stromal infiltrate that was treated with topical corticosteroids. RESULTS/CONCLUSIONS: The patient gradually improved and the stromal infiltrate diminished. The cause of psoriasis and its ocular manifestations remains unknown. A corneal abscess without epithelial infiltration that responds to topical corticosteroid therapy may represent a specific ocular manifestation of psoriasis. PMID- 7785701 TI - Scleromalacia after retinal detachment surgery. AB - PURPOSE/METHODS: A 34-year-old man developed severe scleral thinning with imminent prolapse after conventional retinal detachment repair, including pars plana vitrectomy, endolaser photocoagulation, and perfluoropropane injection. Cadaveric dura mater was used to repair the scleral defect. RESULTS/CONCLUSION: The cause of scleromalacia in this case remains to be determined. Commercially prepared cadaveric dura mater can be successfully used as a tectonic graft for the treatment of scleral thinning. PMID- 7785702 TI - White-centered retinal hemorrhages as an early sign of preeclampsia. AB - PURPOSE/METHOD: We examined a pregnant patient who had symptomatic white-centered retinal hemorrhages. Severe preeclampsia rapidly developed despite the patient not having hypertension, proteinuria, or edema at initial examination. RESULTS/CONCLUSIONS: Retinal hemorrhages gradually resolved without treatment and visual acuity returned to 20/20 six months after emergency delivery of a healthy infant. Retinal or choroidal vascular abnormalities in pregnant patients may be caused by early preeclampsia and immediate obstetric referral is indicated. PMID- 7785704 TI - Duane's retraction syndrome associated with chromosome 4q27-31 segment deletion. AB - PURPOSE/METHOD: A 15-year-old boy with bilateral blepharoptosis, bilateral type 1 Duane's retraction syndrome, and mild learning difficulties underwent chromosomal analysis. RESULTS/CONCLUSIONS: A de novo deletion of a segment of the long arm of chromosome 4 (4q27-31) was found. To our knowledge, no other individuals with this chromosome deletion have Duane's retraction syndrome. The chromosome defect lies close to the epidermal growth factor gene, 4q25, which was recently linked to Rieger's syndrome. We suggest that families with Duane's retraction syndrome should be assessed for linkage to the area of 4q27-31. PMID- 7785703 TI - Branch retinal vein occlusion in a child with ocular sarcoidosis. AB - PURPOSE/METHODS: A 13-year-old girl had unilateral iridocyclitis and periphlebitis. The periphlebitis exacerbated, and macular edema as well as branch retinal vein occlusion developed. The patient was treated with systemic corticosteroids. RESULTS/CONCLUSIONS: The lesions responded well to systemic corticosteroids. Histologic diagnosis of sarcoidosis was obtained by transbronchial lung biopsy. Ocular lesions in this child were similar to those seen in adult sarcoidosis. Branch retinal vein occlusion may occur as a rare vascular complication of sarcoidosis. PMID- 7785705 TI - Tonic pupil and orbital glial-neural hamartoma in infancy. AB - PURPOSE/METHODS: Tonic pupils in early childhood are rare. We studied an otherwise healthy 31/2-month-old girl who had a right pupil that was poorly reactive to light, without other signs of oculomotor nerve palsy. RESULTS/CONCLUSIONS: Constriction of the right pupil after instillation of 0.125% pilocarpine eyedrops confirmed denervation hypersensitivity, consistent with a tonic pupil. There was no strabismus or proptosis. A magnetic resonance imaging scan demonstrated a right orbital mass, interposed between the lateral and inferior recti muscles. Biopsy was consistent with a benign, glial-neural hamartoma. Thus, in this young patient, a tonic pupil was associated with a benign orbital mass. PMID- 7785706 TI - Horner's syndrome in subadventitial carotid artery dissection and the role of magnetic resonance angiography. AB - PURPOSE/METHODS: A 47-year-old man with a postganglionic Horner's syndrome and severe right facial pain was found to have a normal carotid angiogram. We obtained a magnetic resonance angiogram of the neck because of our continued clinical suspicion of dissection. RESULT/CONCLUSION: An area of hyperintensity was identified along the lumen of the right internal carotid artery, suggesting a subadventitial dissection. Magnetic resonance angiography is a noninvasive, sensitive technique for identifying some carotid dissections. PMID- 7785707 TI - Oval defect in detached posterior hyaloid membrane in idiopathic preretinal macular fibrosis. PMID- 7785708 TI - Cyclodeviation in skew deviation. PMID- 7785709 TI - Silicone intubation without intranasal fixation for treatment of congenital nasolacrimal duct obstruction. PMID- 7785710 TI - Progression of nuclear sclerosis and long-term visual results of vitrectomy with transforming growth factor beta-2 for macular holes. PMID- 7785711 TI - Who is the keeper of occupational therapy's practice and knowledge? PMID- 7785713 TI - Reasoning and the art of therapy for spinal cord injury. AB - In this pilot study, qualitative methodology was used to examine the clinical reasoning of four experienced occupational therapists as they presented and modified therapeutic activities to treat patients with spinal cord injuries. The therapists demonstrated the multi-layered thinking discovered in previous research, but hierarchical structuring of knowledge emerged as an unexpectedly dominant theme in their reasoning. Examples of hierarchical thinking about therapeutic activity included creating mental files of therapy tasks and materials sequenced from elementary to advanced and determining the level of difficulty at which to present an activity in order to build the patient's skills in a stepwise manner. The therapists reported that they learned to make decisions about the use of activities in treatment by observing skilled clinicians and by treating patients. PMID- 7785712 TI - Building inclusive community: a challenge for occupational therapy. 1994 Eleanor Clarke Slagle Lecture. AB - Occupational therapy was founded on values of choice, relevance, and active participation in meaningful occupations. To assure choice in daily living, learning, work, and play for persons with disabilities or significant health issues, occupational therapy practitioners are challenged to gain increased understanding of the unique culture and community of each person and family with whom they work; create opportunities for these persons to develop their capabilities in community settings of their choice; promote more interactive models of practice in which the practitioner affects the arrangements between the person and society; work with communities to welcome the gifts of diversity; and develop skill in analyzing environments and facilitating environmental interaction. The environment category of the spatiotemporal adaptation theory is expanded and a communication model for collaboration in building individual community is proposed as means for addressing the challenges. PMID- 7785714 TI - Spherical grip strength in children 3 to 6 years of age. AB - OBJECTIVE: The purpose of this study was to establish normative data on spherical grip strength of children 3 to 6 years of age with the Martin Vigorimeter. METHOD: Two hundred twenty-five preschoolers in the Kalamazoo, Michigan, area were tested with standardized positioning and instructions. The mean of three trials for each hand was used as the grip-strength score. A repeated measure design was used and the right and left hands were alternated during testing to allow a 20-sec rest period between trials. Hand width also was measured in inches from the head of the second metacarpal to the head of the fifth metacarpal. RESULTS: Hand width and grip strength were significantly correlated for both the right (p < .0001) and the left hands (p < .001). Grip strength increased linearly across all of the age groups (p < .001). The results of paired t tests did not show a significant difference in grip strength between the right and left hands or between boys and girls. A table of mean grip-strength scores and hand width measurements along with their standard deviations is presented for clinical use. CONCLUSION: The vigorimeter could be used to assess the grip strength of children with rheumatic disorders without putting excessive pressure on the joints or skin of the hand. PMID- 7785715 TI - Functional capacity evaluations of persons with chronic fatigue immune dysfunction syndrome. AB - Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is estimated to affect 2 to 5 million people in the United States. Despite its high incidence, persons with CFIDS have been neglected by the medical community mainly because there is no singular confirming diagnostic test or proven effective treatment. The CFIDS population is incorrectly stereotyped as upper-middle-class, white, female hypochondriacs; consequently, symptoms often are belittled or ignored. In reality, CFIDS is a severe medical condition that affects women, men, and children of any race and often causes long-term or total disability. The results of a modified functional capacity evaluation developed by the author and completed on 86 persons with CFIDS between 1988 and 1990 confirm that this population has severe physical and cognitive disabilities that affect their professional, familial, and social lives. The results of these evaluations are used to present a profile of persons with CFIDS that can serve as a basis for understanding this population and for guiding intervention. PMID- 7785716 TI - A problem-based learning curriculum for occupational therapy education. AB - To prepare practitioners and researchers who are well equipped to deal with the inevitable myriad changes in health care and in society coming in the 21st century, a new focus is needed in occupational therapy education. In addition to proficiency in clinical skills and technical knowledge, occupational therapy graduates will need outcome competencies underlying the skills of critical reflection. In this article, the author presents (a) the rationale for the need for change in occupational therapy education, (b) key concepts of clinical reasoning and critical reflection pertaining to the outcome such change in occupational therapy education should address, (c) problem-based learning as a process and educational method to prepare occupational therapists in these competencies, and (d) the experience of the Program in Occupational Therapy at Shenandoah University in Winchester, Virginia, in implementing a problem-based learning curriculum. PMID- 7785717 TI - Using the case method to develop clinical reasoning skills in problem-based learning. AB - Clinical reasoning is increasingly recognized as a crucial component of the occupational therapy process. Different types of clinical reasoning used by occupational therapists have been identified, including scientific, procedural, interactive, narrative, conditional, and pragmatic reasoning. This article describes the use of the case method in the University of New Mexico undergraduate occupational therapy curriculum to facilitate development of occupational therapy students' problem-solving and reasoning abilities. The case method is a component of problem-based learning that emphasizes small group work to solve clinical problems that are presented as case studies. Students are presented with a variety of case formulas including paper or written cases, videotape cases, simulated client cases, and real client cases to promote the development of specific types of clinical reasoning. Problem-based learning may also hold promise as an educational strategy for fieldwork students and clinicians. PMID- 7785719 TI - An education program on acquired immunodeficiency syndrome for patients with mental illness. PMID- 7785718 TI - A group approach to mental health fieldwork. AB - Fieldwork opportunities in mental health settings are limited and difficult to find. There is increased pressure for occupational therapy supervisors to accept more students although they have less time to devote to them. This article describes a group approach to training occupational therapy students that was used at one fieldwork site. The occupational therapy staff members were each responsible for specific teaching assignments that allowed them to work with a number of students simultaneously. Program development and evaluation meetings created an alternative forum for exploring ideas and practice issues and for providing guidance and supervision. This approach reduced the amount of time each therapist spent with students, provided students with several role models, and encouraged independent thinking in students. PMID- 7785720 TI - Vestibular rehabilitation with graded occupations. AB - These three case reports are examples of the use of graded, purposeful activities in remediating the symptoms of vestibular disorders. Therapists can design individualized treatment plans for each patient by incorporating activities of interest to the patient. The treatment activities must include the particular head movements and positions that elicit vertigo during assessment. Additionally, activities must be interesting to the individual patient. Use of interesting activities may sustain the patient's interest and motivation for the treatment program and enable the patient to relate the learning process to real life experience. The principle that graded, repetitive head movement exercise is efficacious in reducing vertigo and disequilibrium in patients with vestibular disorders is now well accepted among physicians and therapists who treat these patients. The principle of adding meaning or purpose to otherwise rote exercise is well accepted among occupational therapists and is supported by evidence from the empirical literature (Heck, 1988; Kircher, 1984; Yoder, Nelson, & Smith, 1989). This concept of adding purpose to repetitive exercise may now be extended to the treatment of patients with peripheral vestibular disorders. PMID- 7785721 TI - Certified occupational therapy assistants need a name change: a response to Hirama. PMID- 7785722 TI - Ohalo II H2: a 19,000-year-old skeleton from a water-logged site at the Sea of Galilee, Israel. AB - The discovery of well-preserved human remains at the site of Ohalo II in the northern Jordan Valley substantially augments the meager fossil record of the Levantine late Upper Pleistocene. The Ohalo II H2 specimen, dated to ca. 19,000 B.P., is the most complete early Epipaleolithic hominid discovered in Israel and promises to contribute to the clarification of a number of problematic issues in the local evolution of anatomically modern humans. In addition to a description of the burial and its Kebaran context, a detailed anatomical description of the skeleton is offered and morphometric comparisons are made to other Upper Paleolithic hominids. Ohalo II H2 is shown to demonstrate affinities in the craniofacial skeleton to fossils from the early Upper Paleolithic and late Epi Paleolithic of the Levant. PMID- 7785723 TI - Faunal assemblage seriation of southern African Pliocene and Pleistocene fossil deposits. AB - Fossil assemblages from the Pliocene and Pleistocene of southern Africa were seriated in order to give a better idea of their relative chronology. Time sensitive mammals were selected for calculation of the Faunal Resemblance Index among 17 site units. On the basis of a logistical seriation and subsequent site analysis, the following sequence of sites was deemed most probable: Makapansgat Member 3, Makapansgat Member 4, Taung Dart deposits, Sterkfontein Member 4 and Taung Hrdlicka deposits, Sterkfontein Member 5 (in part) and Kromdraai B, Kromdraai A and Swartkrans Member 1, Swartkrans Member 2, Swartkrans Member 3, Plovers Lake, Cornelia, Elandsfontein Main Site, Cave of Hearths Acheulian levels, Florisbad and Equus Cave and Klasies River Mouth. PMID- 7785724 TI - Sexual dimorphism in the snub-nosed langurs (Colobinae: Rhinopithecus). AB - Sexual dimorphism in the dentition and skeleton of the four extant species of snub-nosed langurs, Rhinopithecus (R.) bieti, R. (R.) brelichi, R. (R.) roxellana and R. (Presbytiscus) avunculus, was studied. The species shared a similar general pattern of sexual dimorphism, but were found to differ in respects that appear to reflect the influence of disparate socioecological and environmental factors. All the species showed marked canine dimorphism but the very high degree of canine dimorphism in R. bieti appeared to be due to the intensity of intermale competition for mates during a temporally restricted breeding season, and possibly also to the intensity of competition between males for other resources during other times of the year. Sexual dimorphism in the postcranial skeleton of Rhinopithecus species was also most pronounced in R. bieti and may be related to the relatively higher frequency of terrestrial locomotion in males of the species. PMID- 7785725 TI - Nonlinearity in the relationship between bone Sr/Ca and diet: paleodietary implications. AB - Strontium in archaeological human bones is widely, almost paradigmatically, used as a measure of the relative dietary abundances of plants and meat. Quantitative modeling reveals, however, that there is not a simple proportional relationship between bone strontium and the dietary plant/meat ratio. While knowledge of specific foods and their compositions may permit accurate calculation of average bone strontium levels, knowledge of bone strontium does not inversely allow accurate calculation of specific foods. Although bone strontium quantitatively reflects the average dietary Sr/Ca ratio, it is disproportionately sensitive to high-calcium foods and can be easily affected by minor dietary constituents and culinary practices. Bone strontium, and by analogy, barium, should be seen as a reflection of the high-mineral dietary components rather than a quantitative index of trophic position. PMID- 7785726 TI - Pattern profile analysis of hominid and chimpanzee hand bones. AB - In a study designed to complement morphological research on hominid hand bones, length and width measurements of the thumb, index, and middle rays were obtained from radiographs of modern human hands. These rays are primary in precision gripping postures and are therefore the ones most relevant for investigating evolutionary changes in fine manipulation. Pattern profile analysis allows individuals or samples to be plotted against a reference sample in standard deviation units, or Z-scores. It provides an indication of how different measurements are from modern human averages, while taking into consideration the degree of variation present within modern human samples. A pattern profile for chimpanzees is clearly distinct from humans but quite similar to that of a bonobo, demonstrating the promise of pattern analysis. Partial pattern profiles of several of the more complete early hominid bones from Hadar, Swartkrans, and Olduvai (O.H. 7) are presented and compared. Hadar bones are long and wide at midshaft relative to articular widths; both body-size effects and functional differences are likely. Thumb distal phalanges from Swartkrans and Olduvai both have relatively small base widths, but they differ in other proportions. Two first metacarpals from Swartkrans show distinct patterns. The profiles of La Ferrassie I and Shanidar IV show the characteristically large Neanderthal distal phalanges. Profiles of Skhul IV and Predmost III are alike in some regions with reference to modern North American white males, though they are less similar overall than are those of the two Neanderthals. PMID- 7785727 TI - Enamel hypoplasia in the middle pleistocene hominids from Atapuerca (Spain). AB - The prevalence and chronology of enamel hypoplasias were studied in a hominid dental sample from the Sima de los Huesos (SH) Middle Pleistocene site at the Sierra de Atapuerca (Burgos, northern Spain). A total of 89 permanent maxillary teeth, 143 permanent mandibular teeth, and one deciduous lower canine, belonging to a minimum of 29 individuals, were examined. Excluding the antimeres (16 maxillary and 37 mandibular cases) from the sample, the prevalence of hypoplasias in the permanent dentition is 12.8% (23/179), whereas the deciduous tooth also showed an enamel defect. No statistically significant differences were found between both arcades and between the anterior and postcanine teeth for the prevalence of hypoplasias. In both the maxilla and the mandible the highest frequency of enamel hypoplasias was recorded in the canines. Only one tooth (a permanent upper canine) showed two different enamel defects, and most of the hypoplasias were expressed as faint linear horizontal defects. Taking into account the limitations that the incompleteness of virtually all permanent dentitions imposes, we have estimated that the frequency by individual in the SH hominid sample was not greater than 40%. Most of the hypoplasias occurred between birth and 7 years (N = 18, X = 3.5, SD = 1.3). Both the prevalence and severity of the hypoplasias of the SH hominid sample are significantly less than those of a large Neandertal sample. Furthermore, prehistoric hunter-gatherers and historic agricultural and industrial populations exhibit a prevalence of hypoplasias generally higher than that of the SH hominids. Implications for the survival strategies and life quality of the SH hominids are also discussed. PMID- 7785728 TI - Brief communication: estimation of adult stature from the calcaneus and talus. AB - Calcanei and tali of 100 skeletons in the Hamann-Todd Collection at the Cleveland Museum of Natural History were measured. The skeletons represented 50 males and 50 females distributed equally by race, i.e., whites and blacks. Linear regression equations, with standard errors ranging from 4.09 to 6.11 cm, were derived from these measurements for the purpose of estimating stature. Two independent control samples, including one comprised of remains of American servicemen lost in World War II and the Korea and Vietnam wars, were tested with relatively accurate results. PMID- 7785729 TI - [The treatment of hirsutism]. PMID- 7785730 TI - [So-called familial forms of uterine myoma]. PMID- 7785731 TI - [The transplacental passage and distribution of ceftazidime in the fetal and maternal organs in a 2nd-trimester abortion]. AB - Transplacental passage of ceftazidime was studied in 17 women with second trimester pregnancy which had to be discontinued for medical causes. A single intramuscular injection of the antibiotic resulted in creation of therapeutically active concentrations in fetal blood and organs, amniotic fluid, and placenta. Transplacental passage of ceftazidime from the mother to the fetus was 19.12%, diffusions to the amniotic fluid 14.46%, diffusion to the placenta 48.46%. Ceftazidime may be effective for the prevention and therapy of fetal intrauterine infection and chorioamnionitis. PMID- 7785732 TI - [A prospective study of antipyrine pharmacokinetics in pregnancy]. AB - Pharmacokinetics of a single dose of antipyrin (10 mg/kg) subjected to biotransformation at the expense of microsomal oxidation of its molecule in the liver was studied in 6 healthy nonpregnant women and in 24 women within the frames of a prospective follow-up starting from the early terms of gestation; 7 of these women developed edemas, proteinuria and/or hypertension in the course of follow-up. The results permit us consider that a test with a single antipyrin dose may be used as a marker to characterize drugs with similar metabolic transformations when used in pregnant women. The identity of pharmacokinetic regularities of antipyrin in samples of blood plasma and saliva permit the use of saliva as biological material for assessment of the metabolic profile of pregnant women. The problem of drug therapy in the third trimester is closely connected with specific features of pharmacokinetic profile detected by antipyrin test both in normal and complicated gestation. Our data evidence that the third trimester is characterized by special tension of the metabolic processes. A complicated course is associated with unambiguous changes in the metabolic activity of drugs, this necessitating special attention of a physician to drug dose. PMID- 7785733 TI - [The steroid content of the amniotic fluid in the 1st and 2nd pregnancy trimesters in 21-hydroxylase insufficiency and in fetal central nervous system defects]. AB - A total of 103 samples of amniotic fluid obtained by transabdominal amniocentesis were examined, 52 of these from women at a high risk of giving birth to children with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency and 30 ones with fetuses with different neural tube malformations. 17 Hydroxyprogesterone was found to be a reliable marker indicating the disease in fetuses from the group at risk of hereditary 21-OH deficiency. This marker can be effectively used as early as in the 1 gestation trimester. Fetal CNS defects are associated with hypofunction of the adrenal cortex in the II gestation trimester, observed in 60-63% of cases with hydrocephalus, anencephaly, or microcephaly. Since the function of fetal adrenals is of paramount importance for the development and maturation of a fetus, it should be examined in case of developmental defects of the neural tube, in order to predict the effect of prenatal treatment. PMID- 7785735 TI - [The main trends of research in obstetrics in the 90s]. PMID- 7785736 TI - [The clinical importance of the dopplerometric study of the blood flow in the normal iliac, uterine and ovarian arteries, in myoma and in endometriosis interna of the corpus uteri]. AB - Dopplerometric investigation of pelvic arteries was carried out in 30 women without gynecologic diseases, in 51 patients with internal endometriosis, and 48 ones with uterine myomas. Internal endometriosis of the uterus was found to be characterized by specific qualitative changes in spectral curves of bloodstream velocity in the internal iliac and uterine arteries. Moreover, progressive changes in spectral curves related to dissemination of endometrioid heterotopias were revealed. In patients with uterine myomas combined with internal endometriosis disorders of peripheral circulation typical of endometriosis predominated. PMID- 7785734 TI - [The importance of the vertical transmission of enteroviruses in the epidemiology of congenital viral infections]. AB - A total of 814 newborns were examined using a highly sensitive method of indication of viral antigens. A high incidence of congenital viral infection was revealed: 450 per 1000 live-born children. Enteroviral infections (mainly Coxsackie) ranked first in prevalence. These infections in the newborns are mainly caused by the vertical transmission of enteroviruses from mothers with persistent forms of infections. Virtually all the other viruses (influenza viruses, cytomegalovirus, herpes simplex virus, parainfluenza, measles, and rubella viruses) are detected in the newborns included in the group at a high risk of vertical transmissions of enteroviral infections. In the majority of cases the said viruses were detected in association with enteroviruses. PMID- 7785738 TI - [Changes in the phosphoinositide metabolism in the blood and tissues of benign and malignant uterine tumors]. AB - Measurements of phosphoinositide levels in the blood, immunocompetent cells, and tumors of 105 patients with uterine myomas, 24 patients with cancer of the corpus uteri, and 17 ones with uterine sarcoma showed that the parameters of phosphoinositide metabolism in the blood of patients with tumors of the uterus reliably differed from those in healthy women. The content of phosphatidylinosites and other phosphoinositide fractions in patients with uterine myomas reliably differed from those in patients with malignant tumors of the uterus, this permitting the use of such measurements in the differential diagnosis. Phosphoinositide mechanism of development of tumors of the uterus is discussed, which is related to the "new" phosphoinositides and secondary messengers directly participating in transfer of cell growth signals. PMID- 7785737 TI - [The prevention of the adhesive process after surgical interventions in gynecological patients in the reproductive period]. AB - Dynamic laparoscopy making use of special tubes was carried out in 149 patients (30 with acute inflammatory diseases of the uterine tubes, 80 following reconstructive surgery on the tubes suffering from tuboperitoneal sterility, 9 operated on the internal genitals). Repeated laparoscopic examinations were carried out in the course of 14 days, every 2-3 days. The course of the postoperative period was assessed by the presence of adhesions, hyperemia, edema, and exudation. Adhesions were separated, during mixtures were delivered including antibiotics, corticosteroids, enzymes, rheopolygluquins; chromohydrotubations was carried out. Dynamic laparoscopy in patients with inflammatory diseases of the internal genitals helped detect positive results 2-3 days after intensive care was started and prevent adhesions. This method appears to be particularly valuable if used after inflammatory processes and interventions on the internal genitals in young, more so in nulliparous women planning to have children in future. PMID- 7785739 TI - [Coagulation hemostasis in pregnant women with toxicosis and the effect of vitamin antioxidants]. PMID- 7785740 TI - [The characteristics of uterine hemodynamics during labor pains]. PMID- 7785741 TI - [Labor during the collision of twins]. PMID- 7785742 TI - [The ultrasonic characteristics of breast status in gynecologic patients]. PMID- 7785743 TI - [Memoirs of service on a military ambulance train in World War II]. PMID- 7785744 TI - [The central and peripheral maternal hemodynamics in an uncomplicated course of pregnancy and in EPH gestosis]. PMID- 7785745 TI - [Endothelins and their role in obstetrical pathology]. PMID- 7785746 TI - Clinical experience with Tilavist: an overview of efficacy and safety. AB - A programme of clinical studies was carried out to determine the basic efficacy and safety of 2% nedocromil sodium eye drops (Tilavist) in treating allergic conjunctivitis, in 2,905 patients from 3-76 years of age. Results of all the double-masked placebo comparative studies completed to date-five in vernal keratoconjunctivitis (VKC), five in perennial (PAC) and 16 in seasonal allergic conjunctivitis (SAC)-have been assessed in a statistical overview analysis. Nedocromil sodium, administered four times daily to 153 patients with VKC, was significantly more effective than placebo (155 patients) and in the clinicians' opinion gave good control in 76% of cases, compared with 46% for placebo (p < 0.001). Patients with chronic symptoms of PAC also responded better to nedocromil sodium given four times daily (n = 146) rather than twice daily (n = 86), and significantly more patients (p < 0.001) were effectively controlled by four times daily treatment with nedocromil sodium (72%) than with placebo (47%; n = 156). Twice-daily dosage with nedocromil sodium (n = 677) was adequate for SAC, however, and the treatment was statistically better than placebo (p < 0.01-p < 0.001) whether dosed twice or four times daily. Speed of action was assessed in seven SAC studies in which 79% of all patients (n = 295) using nedocromil sodium had experienced relief of symptoms when questioned, half of them within 15 minutes and 74% during the first hour after dosing. Test treatments were well accepted by both adults and children, and there were no major adverse events. Minor irritations reported more frequently with nedocromil sodium than placebo were stinging or burning of the eyes on application of the drops and a distinctive taste, noted by 5% of the active treatment group (n = 1,552). PMID- 7785747 TI - Comparative therapeutic studies with Tilavist. AB - Comparative clinical trials which include known therapies as well as placebos are essential in constructing a solid basis from which to 'launch' any new drug. This applies especially to eye drops for treatment of seasonal allergic conjunctivitis, where the symptomatology, already dependent on the vagaries of the natural pollen challenge season, is further influenced by a positive washing action of the placebo eye drops. Tilavist (2% nedocromil sodium ophthalmic solution) has therefore been compared with sodium cromoglycate eye drops and non sedating antihistamine tablets, both mainstays in the treatment of seasonal allergy, in a series of double-masked, placebo-controlled, mainly multicentre studies. Nedocromil sodium, twice or four times daily, proved as effective overall as sodium cromoglycate (2% or 4% four times daily) in three seasonal trials, and was the more effective treatment in a study of patients with vernal keratoconjunctivitis. Its efficacy was most evident during peak periods of pollen challenge, when neither placebo nor sodium cromoglycate eye drops controlled breakthrough symptoms. Three further seasonal studies showed nedocromil sodium eye drops to be as effective as standard oral doses of astemizole and terfenadine, whilst a faster onset of action than terfenadine was reported in one multicentre study. PMID- 7785748 TI - Current practice: diagnosis and treatment in primary healthcare. AB - In a primary healthcare facility, there are certain 'rules of thumb' that can be recommended for the diagnosis and treatment of conjunctivitis. The type of discharge is a crucial factor in the differential diagnosis and can also be a clue towards the management in primary care. It is important to identify whether the conjunctivitis is an isolated case or part of another disease, and if it is acute or chronic, and I would suggest taking a smear or culture sample whenever possible. When the aetiology is not clear, I would try antibiotics. If the patient is allergic, and an allergic conjunctivitis is suspected, the best management today is to use mast cell stabilisers, and combine these with conservative measures of frequent washings, and compresses. If the aetiology remains doubtful, or if there is no obvious improvement using these treatments, the patient should be re-evaluated and/or referred to an ophthalmologist or specialist eye centre. The use of corticosteroids for conjunctivitis should certainly be avoided in primary healthcare. Conjunctivitis is often self-limited and the drug-induced consequences of improper management can be far more devastating than the disease itself. PMID- 7785749 TI - The pathophysiology of ocular allergy: current thinking. AB - Seasonal allergic conjunctivitis is the only ocular disease to involve solely Type-1 hypersensitivity, the other main forms of ocular allergy--perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis--each having a more complex immunological basis and a chronic inflammatory component. Involvement of secondary inflammatory cells, particularly eosinophils, in addition to the mast cells resident in the conjunctival substantia propria, can lead to more serious corneal damage with vision-threatening potential. Thoughtful management of allergic conjunctivitis is needed in order to control the ocular inflammation without incurring steroid induced side-effects, and patient education is also an important factor in maintaining optimal allergen avoidance, especially in the more severe and chronic cases. Laboratory models can be helpful in assessing the potential of new drugs, and SWR mice (topically sensitised and challenged with short ragweed) show clinical signs of allergic conjunctivitis, together with mast cell and eosinophil involvement, remarkably similar to the human pathophysiology. The antiinflammatory activity of both steroids and nedocromil sodium observed in this animal model supports therapeutic evidence of the usefulness of second-generation mast cell stabilising drugs in the treatment of ocular allergy. PMID- 7785750 TI - [Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Therapeutic value of treatment with calcium antagonists, hypervolemic hemodilution and induced arterial hypertension]. AB - Only 53%-58% of patients with a subarachnoid haemorrhage (SAB) following the rupture of a cerebral aneurysm survive without neurological damage. Morbidity and mortality are closely related to the delayed ischaemic neurological deficit due to cerebral vasospasm. The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature. PATHOPHYSIOLOGY. In addition to other vasoactive substances in the blood, haemoglobin, which is released from lysed erythrocytes on the 2nd to 4th day after the haemorrhage, plays an important role in inducing vasospasm. An inflammatory angiopathy ensues, with complete resolution after 6-12 weeks. The cerebral blood flow (CBF) is reduced depending on the extent of vasospasm. Irreversible infarction may follow the decrease of CBF below a critical value. Severe vasospasm causes autoregulatory disturbances and reduced responsiveness of cerebral vessels to CO2. CALCIUM ANTAGONISTS. The calcium blocker nimodipine causes dilatation of small pial vessels with increased CBF. However, systemic vasodilation with the subsequent fall in blood pressure may limit the increase in CBF. Furthermore, it is known that nimodipine decreases intracellular calcium concentrations resulting in some protection against ischaemic cellular injury. Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm. HYPERVOLAEMIC HAEMODILUTION. Volume expansion and haemodilution to a hematocrit of 30%-33% is suggested to improve cerebral perfusion during vasospasm. The central venous and pulmonary capillary wedge pressures should be 10-12 mm Hg and 15-18 mm Hg, respectively. But there is no evidence of improved outcome with this measure, and pulmonary edema is a frequent side effect. However, impairment of cerebral perfusion and increased neurological damage can be demonstrated with hypovolaemia and haemoconcentration. INDUCED ARTERIAL HYPERTENSION. In the presence of cerebral vasospasm and resulting autoregulatory disturbances, cerebral perfusion can be increased by raising systemic arterial pressure. This measure, too, fails to improve neurological outcome. CONCLUSION. Treatment of cerebral vasospasm following a SAB aims to avoid any impairment of cerebral perfusion. Hypovolaemia and haemoconcentration have to be corrected. Normoventilation should be established to avoid hypocapnic vasoconstriction. Nimodipine should be administered continuously after a SAB. In view of the autoregulatory disturbances, systemic hypotension with its danger of decreased CBF must be prevented. The importance of hypervolaemic haemodilution and/or induced arterial hypertension is not clear. Despite therapeutic efforts, the number of patients who have survived a SAB without a substantial neurological deficit has not increased. PMID- 7785751 TI - [The role of autologous blood transfusion in the the Federal Republic of Germany. Results of a 1993 questionnaire. 1. The reunited Germany]. AB - The objective of the study was to evaluate the role of autologous blood transfusion in current clinical practice in the Federal Republic of Germany after reunification. METHODS: Questionnaires were sent to the anaesthesia departments of 684 German hospitals in January 1993. The sample consisted of 400 randomly selected hospitals from the former West Germany ("old federal states") and 284 hospitals from the former German Democratic Republic ("new federal states"). Only hospitals with more than 25 surgical beds were included in the study. The questionnaire contained 36 questions related to (1) general information on the hospital, (2) preoperative autologous blood donation (PABD), (3) preoperative plasmapheresis, (4) isovolaemic haemodilution, (5) perioperative blood salvage, and (6) general management of blood transfusion. RESULTS: A total of 502 completed questionnaires (73%) were returned, 305 from hospitals in the "old federal states" and 197 from hospitals in the former German Democratic Republic. Nine per cent of the responding hospitals were running their own transfusion services, and 56% were located in the vicinity of a regional blood bank. The overall proportion of surgical procedures requiring perioperative blood transfusion ranged from 1% to 90% (median 10%). PABD was performed "not at all" in 18%, "rarely" in 20% "occasionally" in 27%, "frequently" in 17%, and "mostly" in 16% of the responding hospitals. The principal use of PABD was in orthopaedic surgery and cardiac surgery (83% and 70% of the departments in question, respectively). In more than 50% of the hospitals reporting, the PABD service was run by the anaesthesia department. Patients not meeting the established criteria for homologous blood donors were accepted for autologous blood donation "frequently" and "mostly" in 20% and 12% of the hospitals, respectively, but at most "occasionally" in 63% of the hospitals. Preoperative plasmapheresis was performed in 12% of the responding hospitals. Autologous fresh frozen plasma predominantly was used for volume replacement, and for prevention of coagulation disorders when major blood loss was anticipated. Isovolaemic haemodilution was performed "not at all" in 28%, "rarely" in 19%, "occasionally" in 28%, "frequently" in 16%, and "mostly" in 8% of the responding hospitals. The reasons most frequently invoked for not performing haemodilution were "too time consuming" and "too little blood-saving effect". Cell separators for perioperative blood salvage were available in 30% of the responding hospitals. Of the other hospitals not equipped with cell-washing devices, 11% performed perioperative blood salvage of unprocessed blood by means of simple collection devices. Some 80% of those hospitals using intraoperative autotransfusion devices also performed blood salvage postoperatively. The principal use of perioperative blood salvage was in cardiac surgery, orthopaedics, and vascular surgery (90%, 54%, and 54% of departments, respectively). Some 48% of the responding anaesthetists "mostly" considered haemoglobin levels of 8-10 g/dl acceptable in patients without cardiopulmonary disease, but only 18% did so in patients with cardiopulmonary disease. CONCLUSIONS: Although available in the majority of hospitals surveyed, the simple techniques of both PABD and isovolaemic haemodilution are unduly neglected in routine clinical practice. The consistent use of both of these techniques, and the careful weighing up of the indication for every single blood transfusion, would not only effectively reduce homologous blood transfusions, but also enable even small hospitals to run successful autologous transfusion programmes without expensive cell-washing and plasmapheresis devices. PMID- 7785752 TI - [Quality control in anesthesiology. Results of a prospective study following the recommendations of the German Society of Anesthesiology and Intensive Care]. AB - The German Social Law has required quality assurance (QA) procedures since 1989. The measures must be suitable to allow "comparing investigations". In 1992 the German Society of Anaesthesiology and Intensive Care Medicine published recommendations for QA in anaesthesia: most problems during an anaesthetic should be documented in a standardised manner, and thus, a list of 63 pitfalls, events, and complications (PECs) and five degrees of severity were defined. The goal of this study was to determine the frequency of PECs in anaesthesia and to correlate PECs with procedures and preoperative health status. MATERIALS AND METHODS. Demographic data, preoperative findings, type and duration of anaesthesia and operation, and kind and severity of PECs were integrated in an automatically readable anaesthetic data record (ARADR). During 12 months all anaesthetics in our department were documented by the ARADR; the records were read by a reading device and the data stored in a modern SQL database (Informix). Degrees of severity: I. PEC leads to reaction of anaesthetist, no impact for recovery room (RR); II. impact for RR, no impact on transfer to ward; III. significant prolongation of RR stay or additional monitoring on ward; IV. PEC leads to intensive care unit admission; V. disabling damage or death. RESULTS. In all, 18350 anaesthetics were recorded (9055 male, 9295 female); the median age was 41 years (1 day-99 years). In 4251 (23.2%) anaesthetics 5927 PECs occurred, 3412 of them involving the cardiovascular and 949 the respiratory system, the latter with a tendency to higher degrees of severity. PECs caused by technical equipment (126) or lesions caused by anaesthesists (342) had no fatal outcomes and were less severe. Patients in ASA class I had 12.3% anaesthetics with PECs, ASA II 23.3%, ASA III 33.8%, ASA IV 34.9%, and ASA V 58.5%. PECs of degrees IV and V showed a higher incidence in the higher ASA classes. There was no fatal PEC in an ASA class I patient and only one (of 13615) in an elective procedure. Emergency cases had more frequent and more severe PECs: 16 of 19 PECs of degree V were in ASA class IV and V patients and 15 in emergency situations, all of them in surgical patients. Patients with cardiovascular disease had a more frequent incidence of PECs by a factor of 1.39 to 5.93 than those without such disease. CONCLUSIONS. Standardised incident reporting by defined PECs seems a good way to describe problems in anaesthesia. The types of PECs in our study had a similar distribution to those in other investigations, but there was a tendency to less frequent fatal PECs in ASA classes I to IV and more frequent ones in ASA class V. We expect better comparability when multicenter studies are done using identical methods in the next few years. Perhaps different patients collectives with special risks will be detected; efforts in quality improvement could focus on these patients. PMID- 7785753 TI - [Anesthesia for heart transplantation in newborn and suckling infants. Special aspects of the hypoplastic left heart syndrome]. AB - Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres. PMID- 7785754 TI - [Operations with a heart-lung machine in adult members of Jehovah's Witnesses]. AB - Members of Jehovah's Witnesses refuse blood transfusions and blood products under any circumstances. Because of an improvement in blood salvage techniques in our centre, they are not excluded from open-heart surgery. In recent years recombinant human erythropoietin (rhEPO) has been applied to correct perioperative anemia in these patients. METHODS. Seventeen members of Jehovah's Witnesses who were more than 18 years of age were operated on using various blood salvage technique, e.g., haemoseparation and a high dose of Aprotinin. We present the first three patients treated with 4 x 500 U of i.v. rhEPO/kg body wt. given within 11 days preoperatively. Thirteen of the patients operated on had elevated preoperative risk factors, for instance poor left ventricle, severe aortic valve stenosis, metabolic syndrome, age older than 70 years, etc. In other centres that perform cardiac operations on members of Jehovah's Witnesses, these risk factors represent contraindications for open-heart surgery in these patients. RESULTS. Patients with rhEPO treatment showed a preoperative hematocrit increase of 7 Vol.% within 10 days and no postoperative complications. At the 6th postoperative hour the hematocrit returned to the starting values; in patients without rhEPO, however, the hematocrit generally had not increased to preoperative values even by the 8th day after operation. In 9 patients with preoperative elevated risk factors and a postoperative relative decrease in hematocrit below 33% we observed an uncomplicated postoperative period. Four patients with these risk factors, a pronounced decrease in hematocrit and blood loss postoperatively had various severe complications. CONCLUSIONS. Preoperative treatment with a high dose of rhEPO to enhance the hematocrit and maturity by precursor red blood cells in patients with a hematocrit below 45 Vol.% is a possibility to compensate for the blood loss perioperatively and to avoid complications from a decrease in oxygen transport capacity. The anaemia and high blood loss postoperatively are the main causes for a slightly elevated operation risk in members of Jehovah's Witnesses in all heart centres that perform cardiac operations on these patients. Nevertheless, Jehovah's Witnesses should be not excluded from cardiac operations, since open-heart surgery without use of homologous blood is becoming a routine procedure. PMID- 7785755 TI - [Postoperative pulmonary function after lung surgery. Total intravenous anesthesia with propofol in comparison to balanced anesthesia with isoflurane]. AB - After lung resection, early extubation and the rapid return of the patients ability to cooperate is the predominant goal. Propofol anaesthesia is characterised by rapid awakening and recovery of cognitive and psychomotor functions and is consequently desirable for such operations. Experience so far in lung surgery, however, is limited. Besides the level of consciousness we investigated various spirometric parameters after lung resection. Total intravenous anaesthesia was performed with propofol, while balanced anaesthesia was performed with isoflurane. METHODS. A total of 93 patients evaluated electively for wedge excision or lobectomy were enrolled in an open, prospective, randomised, interindividual comparative study. Sixty-three patients could be evaluated with complete data sets. In the evening and the morning before the operation the patients were premedicated orally with clorazepate 0.5-0.7 mg/kg. Anaesthesia was induced in group 1 with propofol (1.0-2.5 mg/kg) and maintained with propofol (4-12 mg/kg) in 50% O2/air. The patients in group 2 received methohexital (1-2 mg/kg) for induction and isoflurane (0.4-2.0 vol%) in 50% O2/air for the maintenance of general anaesthesia. In both groups analgesia was achieved by using fentanyl (up to 10 micrograms/kg) and muscle relaxation by using atracurium. Psychomotor tests (minimal mental state, reaction time) were performed the day before the operation (t1), immediately prior to induction of anaesthesia (t2) and 5 min, 30 min, 60 min, 90 min, 24 h, and 7 days after extubation (t3-t8). Spirometry (forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC; peak expiratory flow, PEF) was carried out at times t1, t2 and t5-t8. RESULTS. The two groups were comparable regarding preoperative status (age, sex, preoperative risk score, psychomotor tests, and spirometric values) and the operation performed (wedge excision/lobectomy, duration of anaesthesia). The extubation time was slightly shorter in the propofol group (18 +/- 8 min) than in the isoflurane group (20 +/- 6 min). Also, the results of the psychomotor tests were somewhat better in the propofol group than those in the isoflurane group. The clearest differences were found in the early postoperative period, but not all differences were significant. Statistically highly significant differences between the two groups were found for the three spirometric parameters. Based on the FEV1 value of the 7th postoperative day, FEV1 taken 60 min after extubation declined by 27.9% in the propofol group vs. 51.7% in the isoflurane group (P = 0.01). At 90 min after extubation the corresponding decline in the propofol group was 26.6%, in the isoflurane group 51.1% (P = 0.003). In addition, the decline of FVC and PEF measured 60 min and 90 min after extubation was significantly smaller in the propofol group than in the isoflurane group. CONCLUSION. The postoperative impairment of lung function after lung resection under propofol anaesthesia is statistically significantly smaller than under isoflurane anaesthesia. Total intravenous anaesthesia with propofol is particularly suitable for this kind of operation. PMID- 7785757 TI - [Three isoflurane preparations from various manufacturers. A comparison of isoflurane concentrations in fresh gas after vaporization with a Drager vaporizer type 19.3]. AB - OBJECTIVES: The purpose of this study was to check the precision of the Drager vaporizer model 19.3 when filled with three different preparations of isoflurane. METHODS: Six Drager vaporizers model 19.3 calibrated with forene were filled with forene (Abbott), isoflurane (Lilly) and isoflurane (Pharmacia); gas output was measured by infrared absorption (Irina, Drager) at vaporizer settings of 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 and 5.0 vol%, starting with a fresh gas flow of 2 1/min followed by 4, 6 and 12 1/min. Thus each of the three isoflurane preparations was checked in six different vaporizers and with four different fresh gas flows. RESULTS: Within the concentration range used in clinical practice there was no significant difference in the delivery of the three isoflurane preparations. Each of the six vaporizers produced a controllable and predictable concentration of the three preparations. CONCLUSION: Vaporizers of Drager type 19.n calibrated with forene deliver the same predictable concentration of the volatile anaesthetic when filled with isoflurane from Lilly or isoflurane from Pharmacia instead of forene and may be used without impairment in patient safety. In addition, no specific calibration with one of the new isoflurane preparations is required. PMID- 7785756 TI - [Heat and moisture exchangers for conditioning of inspired air of intubated patients in intensive care. The humidification properties of passive air exchangers under clinical conditions]. AB - Heat and moisture exchangers (HME) are used as artificial noses for intubated patients to prevent tracheo-bronchial or pulmonary damage resulting from dry and cold inspired gases. HME are mounted directly on the tracheal tube, where they collect a large fraction of the heat and moisture of the expired air, adding this to the subsequent inspired breath. The effective performance depends on the water retention capacity of the HME: the amount of water added to the inspired gas cannot exceed the stored water uptake of the previous breath. This study evaluates the efficiency of four different HME under laboratory and clinical conditions using a new moisture-measuring device. METHODS. In a first step, the absolute efficiency of four different HME (DAR Hygrobac, Gibeck Humid-Vent 2P, Pall BB 22-15 T, and Pall BB 100) was evaluated using a lung model simulating physiological heat and humidity conditions of the upper airways. The model was ventilated with tidal volumes of 500, 1,000, and 1,500 ml and different flow rates. The water content of the ventilated air was determined between tracheal tube and HME using a new high-resolution humidity meter and compared with the absolute water loss of the exhaled air at the gas outlet of a Siemens Servo C ventilator measured with a dew-point hygrometer. Secondly, the moisturizing efficiency was evaluated under clinical conditions in an intensive care unit with 25 intubated patients. Maintaining the ventilatory conditions for each patient, the HME were randomly changed. The humidity data were determined as described above and compared with the laboratory findings. RESULTS AND DISCUSSION. The water content at the respirator outlet is inversely equivalent to the humidity of the inspired gases and represents the water loss from the respiratory tract if the patient is ventilated with dry gases. Moisture retention and heating capacity decreased with higher volumes and higher flow rates. These data are simple to obtain without affecting the patient and can easily be interpreted. It was demonstrated that, compared to physiological conditions, the DAR Hygrobac and Gibeck Humid Vent 2P-HME coated with hygroscopic salts-were able to maintain sufficient inspiratory humidity and heat. The Pall-HME, solely a condensation humidifier, did not meet the physiological requirements. PMID- 7785758 TI - [Intravenous administration of ondansetron vs. metoclopramide for the prophylaxis of postoperative nausea and vomiting]. AB - This randomized, double-blind, multicentre, parallel-group study compared the efficacy and safety of an intravenous dose of ondansetron 4 mg for the prevention of postoperative nausea and vomiting (PONV) with metoclopramide 10 mg and placebo in patients undergoing major gynaecological surgery. A total of 1044 patients (465 ondansetron, 462 metoclopramide, 117 placebo) received study medication immediately prior to induction of anaesthesia and were included in the analysis of data. The proportion of patients experiencing no emesis and no nausea or provided with rescue antiemetic medication, the number of emetic episodes, and the duration and severity of nausea were recorded during the 24-h period after recovery. Significantly more patients who received ondansetron had no emetic episodes (44%) than those who received metoclopramide (36%, P = 0.049) or placebo (25%, P < 0.001). A higher proportion of patients receiving ondansetron (32%) did not experience nausea (metoclopramide 24%, P = 0.009; placebo 16%, P < 0.001). Significantly fewer patients in the ondansetron group required rescue medication or were withdrawn due to treatment failure (P < 0.05). In the ondansetron group the total number of emetic episodes, the median time to the first emetic episode or treatment failure, and the duration and severity of nausea were reduced significantly compared with metoclopramide or placebo (P < 0.05). The safety profile was similar for each treatment group. PMID- 7785759 TI - [Controlled hypotension]. AB - Induced hypotension is defined as a reduction in mean arterial blood pressure to 50-60 mm Hg in normotensive subjects. The aim of induced hypotension is to decrease intraoperative blood loss, decrease the need for blood transfusions and improve operating conditions. Most studies indicate that induced hypotension can decrease intraoperative blood loss by 50% in many surgical procedures; however, some studies report that blood loss is not significantly reduced. Current methods of induced hypotension are based on the use of rapid and short-acting vasodilators as primary agents (nitroprusside, nitroglycerine, urapidil), supplemented by volatile anesthetics (isoflurane) and/or beta-blockers (esmolol) to improve effect, reduce dosage and prevent side effects (reflex tachycardia, tachyphylaxis, rebound hypertension). Proper positioning of the patient and controlled ventilation aid in reducing blood loss. Major risks of induced hypotension are a reduction in blood flow (i.e. ischaemia) of vital organs (brain, myocardium) and elevation of intracranial pressure in neurosurgical patients. Thus, major contraindications of induced hypotension are severe coronary artery disease, hypertension combined with arteriosclerosis of cerebral vessels and increased intracranial pressure in patients with cerebral disease. Complications are rare in otherwise healthy patients, but may be higher in elderly patients and those with underlying organ dysfunction. Therefore, careful assessment and selection of patients, together with consideration of the potential complications, appropriate choice of drugs and invasive beat-by-beat monitoring, are essential for the safe practice of induced hypotension. PMID- 7785760 TI - Development and application of a fluorometric assay for mammalian membrane dipeptidase. AB - Membrane dipeptidase (EC 3.4.13.19) is a widely distributed mammalian cell surface enzyme involved in the metabolism of glutathione, leukotriene D4, and certain beta-lactam antibiotics. In this study we have developed a sensitive and rapid assay for membrane dipeptidase based on the fluorometric detection of the D Phe released from the model substrate Gly-D-Phe. The released D-Phe is first acted on by D-amino acid oxidase in the presence of flavin adenine dinucleotide. The resulting hydrogen peroxide is then metabolized by peroxidase in the presence of the acceptor substrate p-hydroxyphenylacetic acid which is converted to a highly fluorescent compound. The assay configuration is sensitive down to 0.1 nmol D-Phe and can accurately measure membrane dipeptidase activity even in the presence of large amounts of contaminating protein. The membrane dipeptidase assay and the subsequent fluorometric detection of the released D-Phe can be performed in microtiter plates, thus taking less than 1 h to process 96 samples. This sensitive and rapid assay will be useful for the routine measurement of membrane dipeptidase activity in a number of different applications. PMID- 7785761 TI - Isotopomer study of lipogenesis in human hepatoma cells in culture: contribution of carbon and hydrogen atoms from glucose. AB - Recent developments in the application of stable isotopes and mass spectrometry have permitted the estimation of precursor enrichment and fractional synthesis of the product through mass isotopomer analysis. Thus, the application of isotopomer analysis in studies with 2H- and 13C-labeled glucose may potentially overcome the limitations of traditional methods which can only estimate the fractional use of carbon and hydrogen from glucose for lipogenesis. To illustrate this approach, isotope incorporation and mass isotopomer distribution were determined in fatty acids and cholesterol from a hepatoma cell line (Hep G2) grown in media containing specific (C1 or C6) 2H- or 13C-labeled glucose. Using the binomial model, the respective precursor enrichment, and fractional synthesis of palmitate, stearate and cholesterol were determined using mass isotopomer distribution analysis. In 1 week, 80% of palmitate, 65.5% of stearate, and 50% of cholesterol molecules in the cell extract were derived from de novo synthesis. Under serum-free condition, glucose contributed about 80% of the carbon of the newly synthesized lipids. Using the relative isotope yield of [1-13C] and [6 13C]glucose and a standard formula, the contribution of the pentose pathway to glucose catabolism was calculated to be 4.7%. Fractional syntheses of palmitate, stearate, and cholesterol determined using [1-2H]glucose agreed well with values determined using 13C-labeled glucose. After correcting for the contribution of deuterium label from the glycolytic pathway, the deuterium from [1-2H]glucose contributed 4.7% of the total reducing equivalents for lipogenesis. Unlike radioisotope studies, the stable isotope approach provides information from the perspective of the product and insight into the economy of acetyl units and reducing equivalents which were otherwise not available. PMID- 7785762 TI - A complete platelet system for metabolic studies: pure, defined, and viable over 8 hours. AB - We have been using a human platelet preparation to investigate various aspects of cellular metabolism. These experiments require a pure, quantitated platelet preparation that is viable for up to 8 h. The purity of the preparation has previously been characterized and we have now assessed its viability over 8 h and developed a simple spectrophotometric counting method. This method of counting results in estimations that are within 6% of those from an electronic cell counter (Coulter). Pure platelets stored in a Hepes physiological saline were resuspended periodically in autologous plasma to assess function over 24 h. The platelets consumed oxygen, changed shape, aggregated, and released dense granule ATP at all times. There was a slow and linear decrease in the various processes with time, ranging from 1.7% per hour for oxygen consumption to 3.8% per hour for percentage aggregation. The preparation is therefore not stable, but the changes with time are small and defined and it represents a useful system for the study of platelet and cell biology. PMID- 7785763 TI - Preparation and characterization of RNA standards for use in quantitative branched DNA hybridization assays. AB - RNA standards were developed for use in quantitative hybridization assays such as the Quantiplex HCV RNA Assay and Quantiplex HIV RNA Assay, which are based on branched DNA signal amplification. In vitro transcripts ranging in size from 0.5 to 9.4 kb were prepared and purified by phenol extraction following gel electrophoresis or column chromatography. Aliquots of the transcripts were digested to nucleosides and phosphate and then quantified by phosphate analysis against the U.S. National Institute of Standards and Technology phosphate standard. The quantitation was checked by OD260 and by either hyperchromicity or isotopic tracer analysis. The quantitation of each lot of RNA agreed within 20% by the three methods. The reproducibility of the methods was tested by preparing a total of 13 lots of standard RNAs. The average percentage full-length RNA of the 13 lots was 82%, with a range of 59 to 97%. The standard RNAs were used to test the ability of the branched DNA hybridization assay to quantify all target RNAs accurately regardless of size or slight variations in sequence. Standard Hepatitis C virus (HCV) RNAs of 1.3, 2.2, and 3.2 kb showed that size has no detectable effect on quantitation in the branched DNA hybridization assay. Three different lots of standard 3.2-kb HCV RNA were serially diluted and quantified over a thousand-fold range in the branched DNA hybridization assay. The average signal per attomole of target varied by less than 20% among the 3 lots. Standard HCV RNA transcripts were also prepared from clones of HCV subtypes 1b and 3a to study the effects of target sequence diversity and probe design on quantitation by hybridization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785764 TI - Identification of neutral and sialyl N-linked oligosaccharide structures from human serum glycoproteins using three kinds of high-performance liquid chromatography. AB - The distribution of neutral and sialyl N-linked oligosaccharides from human serum glycoproteins has been studied using three kinds of HPLC columns as described below. N-linked oligosaccharides were released from chymotrypsin- and trypsin digested glycopeptides of human serum by means of glycoamidase (from almond) digestion. The reducing ends of the oligosaccharides were derivatized with the fluorescent reagent 2-aminopyridine (PA). The mixture of PA-oligosaccharides was separated by high-performance liquid chromatography on a diethylaminoethyl column according to the sialic acid content. Each fraction separated was then applied on an octadecylsilyl (ODS) column, and the elution volume of each peak was recorded as a glucose unit on the X-axis. Then, each of the separated oligosaccharides was applied to the amide column. Each peak's elution volume was recorded as a glucose unit on the Y-axis. The elution volumes from these two columns (ODS and amide) provide a unique set of coordinates. The structure of each sialyl oligosaccharide fraction was analyzed by the same two-dimensional sugar-mapping technique as previously developed for neutral oligosaccharides. This was combined with exoglycosidase digestion and high-resolution proton NMR measurement. Fourteen neutral, eight mon-sialyl, four di-sialyl, and five tri-sialyl oligosaccharides were isolated from human serum and their structures were characterized. PMID- 7785765 TI - Fluorescence-based enzymatic assay by capillary electrophoresis laser-induced fluorescence detection for the determination of a few beta-galactosidase molecules. AB - beta-Galactosidase can be assayed by monitoring the generation of the fluorescent products, fluorescein-mono-beta-D-galactopyranoside and fluorescein, when the fluorogenic substrate fluorescein-di-beta-D-galactopyranoside is used. We have used capillary electrophoresis with ultrasensitive laser-induced fluorescence detection to monitor the formation of the fluorescent products of off-column enzymatic reactions. By analyzing as little as 40 pl of the enzymatic mixture we obtain limits of detection of 6.5 x 10(-14) M beta-galactosidase or 1.6 molecules based on the detection of fluorescein-mono-beta-D-galactopyranoside. PMID- 7785767 TI - An assay for galactosyltransferase-I activity in articular cartilage. AB - UDP-D-Galactose:D-xylose galactosyltransferase (Galactosyltransferase-I) is an enzyme involved in the synthesis of the linkage region of chondroitin sulfate. Measurement of galactosyltransferase-I in mature articular cartilage has depended on milling such tissue in liquid nitrogen to break open the cells and enable interaction of exogenous substrates with galactosyltransferase-I. This process requires large amounts (approximately 1 g wet wt) of cartilage. This paper reports the development of an assay for galactosyltransferase-I in articular cartilage where 10-25 mg (wet wt) of the tissue was extracted with a buffer containing the detergent Thesit. This assay was more time efficient, required less tissue, and was linear for up to 6 h. It was effective on both mature bovine articular cartilage and embryonic chick epiphyseal cartilage, detecting 100 and 68% of total galactosyltransferase-I activity, respectively. The higher number of measurements available allowed kinetic studies to be conducted on bovine articular cartilage explant cultures under conditions of up- and down-regulation. Incubation with fetal calf serum resulted in an increase in galactosyltransferase I activity. Galactosyltransferase-I activity, however, did not change markedly in cartilage cultured in the absence of fetal calf serum or in the presence of cycloheximide. A soluble preparation of galactosyltransferase-I, extracted from bovine articular cartilage using Thesit, eluted from a Superose-6 column, with a molecular mass of about 55 kDa. PMID- 7785766 TI - Simplified high-sensitivity sequencing of a major histocompatibility complex class I-associated immunoreactive peptide using matrix-assisted laser desorption/ionization mass spectrometry. AB - Cytotoxic T cells (CTL) are known to recognize small peptide fragments of cytoplasmic proteins bound to major histocompatibility complex (MHC) class I molecules on cell surfaces. Recent work indicates that tumor antigens are processed and presented in a manner similar to viral antigens. Identification of the peptides recognized by tumor-specific CTL would provide valuable information about their parent proteins, as well as allowing for the development of recombinant antigen-specific tumor vaccines. While highly represented MHC-bound peptides have been routinely purified by reversed-phase HPLC for Edman degradation sequencing, identification and sequencing of infrequent peptides that represent the biologically relevant targets of tumor-specific CTL have proved elusive. We have combined matrix-assisted laser desorption/ionization mass spectrometry with on-slide exopeptidase digestion to successfully identify and directly sequence a model tumor-specific peptide antigen derived from an integrated viral gene. The enhanced sensitivity of this technique (femtomolar range) allows for the sequencing of specific MHC-bound peptides derived from as few as 1 x 10(9) cells. PMID- 7785769 TI - Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors. AB - The development of noninvasive optical studies necessitates an understanding of the biological parameters which affect light propagation in soft tissues. In the present report, we have measured the optical properties of various normal (i.e., perfused liver, brain, skeletal muscle, white adipose tissue) and neoplastic rodent tissues (i.e., glioma, hepatoma, mammary adenocarcinoma) by using time resolved spectroscopy. The contribution of the hemoglobin (+ myoglobin in the case of muscle) to the total light absorption at 780 nm has been determined. This contribution varies from about 25% (brain, skeletal muscle) to about 100% (white adipose tissue, 13762A mammary adenocarcinoma, 9L glioma). These results are explained by different blood volume fractions in the tissues and by the existence at 780 nm of other chromophores, such as the mitochondrial cytochrome oxidase. Secondly, the dependence of the light scattering of the tissue on both the cell and the mitochondrial content has been analyzed. The results indicate that there is no correlation between the light scattering and the DNA content, measured as an indicator of the cell number in the tissue. The scattering coefficient is proportional to both the succinate dehydrogenase activity and the mitochondrial protein content of the tissue, which are indicators of the mitochondria content of the tissue when based upon estimates of tissue wet weight. PMID- 7785770 TI - Separation of neutral asparagine-linked oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection. PMID- 7785768 TI - A bisulfite method of 5-methylcytosine mapping that minimizes template degradation. AB - The bisulfite method is a highly sensitive approach to 5-methylcytosine mapping that utilizes the capability of the polymerase chain reaction to exponentially amplify DNA. We have observed that the bisulfite reaction results in a significant level of template degradation due to DNA depurination. Furthermore, our data suggest that the DNA fragmentation which occurs limits the sensitivity of the method. We describe a simple solution to limit degradation of the DNA template. PMID- 7785771 TI - Acetyl phosphate as an energy source for bacterial cell-free translation systems. PMID- 7785773 TI - Quantitative determination of protamines by coomassie blue G assay. PMID- 7785772 TI - Localization of epitopes for monoclonal antibodies directed against the adult rat skeletal muscle sodium channel (rSkM1) using polymerase chain reaction, fusion proteins, and western blotting. PMID- 7785774 TI - Reverse electrophoresis to concentrate DNA fractions. PMID- 7785776 TI - Reduction of strong lipase-polyclonal antibodies binding by limited proteolysis. AB - Initial attempts to purify Geotrichum candidum lipase (EC 3.1.1.3) using immunoaffinity chromatography have been hampered by the tight binding of the lipase to the immobilized rabbit anti-GCL IgG. Stringent elution conditions were unable to release more than a few percent of the antigen. To decrease the tight binding, the immunosorbent was treated with minute amounts of different proteases, of which elastase proved to be most effective. Using the elastase treated immunosorbent both natural and recombinant GCL II were purified to homogeneity with 30% of lipase recovered from the immunoaffinity chromatography step. PMID- 7785775 TI - A comparison of methods for determining total body protein. AB - The aim of the study was to find the optimal method (with respect to convenience and accuracy) for determining total protein in whole-body homogenates of rats. Three different protein extraction methods and five different protein concentration methods were assessed. The results were compared against a reference value measured by complete amino acid analysis after acid hydrolysis. The data demonstrated that extraction with 5% (w/v) sodium dodecylsulfate (SDS) in 0.5 N NaOH was far superior to that with water alone or to 6 N guanidine-HCl. A comparison of the Biuret, Bradford, and bicinchoninic acid methods on the SDS NaOH-extracted samples showed that the Biuret method was optimal, giving a value that was 90% of the reference value with a small variation (2.4% of the mean). The Kjeldahl method gave the correct protein concentration only when a nitrogen factor of 5.51 +/- 0.03 (N = 5) was applied. The results suggest that extraction with SDS-NaOH followed by the Biuret procedure is a good method for measuring protein concentrations in whole body rat homogenates. PMID- 7785777 TI - Precipitation of Hevea brasiliensis latex proteins with trichloroacetic acid and phosphotungstic acid in preparation for the Lowry protein assay. AB - Many proteins derived from the latex of Hevea brasiliensis that remain soluble in trichloroacetic acid (TCA) can be precipitated by phosphotungstic acid (PTA). A combination of 5% TCA and 0.2% PTA precipitates a wide range of proteins effectively even when they are present in low concentrations (below 1 microgram ml-1). In addition to its protein purification function, acid precipitation also increases the sensitivity of the subsequent protein assay by allowing the test sample to be concentrated. Another advantage of protein precipitation by TCA and PTA is that very small amounts of protein (of the order of 10 micrograms) can be repeatably recovered without the use of precipitate-bulking agents such as sodium deoxycholate. This general procedure of protein purification and concentration is simple and rapid, but the use of PTA may not be fully compatible with the Bradford protein assay. A modified Lowry microassay is described which enables about 3 micrograms ml-1 to be quantitated at the photometric absorbance of 0.05. When used in conjunction with protein concentration by precipitating with TCA/PTA, approximately 0.4 microgram ml-1 protein present in 6 ml of solution can be assayed. PMID- 7785778 TI - A double labeling procedure for lipoproteins: independent visualization of dual ligand-receptor interaction with colloidal gold- and 125I-labeled ligands. AB - The analysis of multiple ligand binding to a single receptor molecule poses a methodological challenge. The chicken oocyte 95-kDa receptor for the uptake of the two major yolk lipoprotein precursors very low-density lipoprotein (VLDL) and vitellogenin (VTG) is such a multipotent transport receptor. Here we describe methods for rapid independent and simultaneous analysis of VLDL and VTG binding to this receptor, termed VLDL/VTG receptor. First, further development of a one step labeling protocol for chicken lipoproteins with colloidal gold (Au) to visualize independently the binding of VLDL and VTG to the chicken VLDL/VTG receptor is reported. The advantage of this protocol is that the preparation of the Au-lipoprotein conjugates is rapid, and utilization of Au-lipoprotein complexes in ligand blots does not require their further purification, while signal enhancement by silver staining is still applicable. Second, the simultaneous use of 125I- and Au-labeled ligands in a one-step ligand blotting procedure facilitates the direct demonstration of the competitive interaction of VLDL and VTG with the receptor. Following sequential processing of the nitrocellulose strips, binding of differently labeled ligands can be studied independently. In summary, we describe a procedure for differential labeling of lipoproteins and its application toward the analysis of receptors that bind more than one ligand. PMID- 7785779 TI - Correlation of electrophoretic mobilities of proteins and peptides with their physicochemical properties. AB - Electrophoretic mobilities, mu, of nine proteins (M(r) 14,200 to 70,000) in 28 mM Tris/47 mM glycine buffer at pH 8.77 and 5 mM ionic strength were measured by laser Doppler velocimetry and correlated to ratios of charge (q) to molecular weight (M(r)) and shape factor (f/f0) by the equation mu(f/f0) = (Aq/Mpr-B). This correlation was previously reported for peptides and proteins for mu measured at 100 mM ionic strength. When A = 6.048 x 10(-3), B = 1.13 x 10(-5), and p = 2/3, the correlation fitted 51 measured and literature values over the molecular weight range of 178 to 140,000 for components whose electrophoretic mobilities ranged from +13.35 x 10(-5) to -19.7 x 10(-5) cm2/(V.s). The experimental measurements confirm the general suitability of p = 2/3 and show that the familiar charge/mass relation for electrophoresis is applicable to proteins in low-ionic-strength buffers which are typical of electrochromatography systems. Extrapolation of the correlation to different ionic strengths indicates that a low-ionic-strength buffer amplifies differences of electrophoretic mobility as a function of charge/mass, while high ionic strength diminishes such differences. PMID- 7785781 TI - A continuous spectrophotometric assay for protein phosphatases. AB - A continuous spectrophotometric assay for the determination of protein phosphatase activity is presented. The assay incorporates the coupled enzyme system of Webb (M. R. Webb, 1992, Proc. Natl. Acad. Sci. USA 89, 4884-4887), which used purine nucleoside phosphorylase and the chromophoric substrate 7 methyl-6-thioguanosine for the quantitation of inorganic phosphate. The assay is exemplified and validated here for the phosphorylase phosphatase activity of protamine-stimulated protein phosphatase 2A1 (PP-2A1). The effects of reaction components on the activities of both PP-2A1 and purine nucleoside phosphorylase were studied. The application of the coupled assay system to kinetic analysis of the phosphorylase phosphatase activity of PP-2A1 and to the assay of the catalytic subunits of type 1 and 2A protein phosphatases and a recombinant type 1 catalytic subunit is demonstrated. The applicability of this coupled enzyme system to the assay of other protein phosphatases is discussed. PMID- 7785780 TI - Imaging and quantitation of chemiluminescence using photoexcitable storage phosphor screen. AB - A novel storage phosphor (SrS:Ce,Sm) imaging screen optimized for the detection of luminescence has been developed. When coupled with an appropriate scanning system, this screen exhibits the following characteristics: (i) a range of visible light detection between 400 and 500 nm with a peak response at 450 nm; (ii) sensitivity comparable to X-ray film; (iii) 200-microns resolution; (iv) linear dynamic range greater than four orders of magnitude; and (v) a uniformity of response of +/- 1.32% coefficient of variation. These features facilitate the detection and accurate quantitation of light radiation produced from the enzymatic catalysis of chemiluminescent substrates such as 1,2-dioxetanes and luminol. Its suitability for chemiluminescent applications is demonstrated by the analysis of cosmid hybridization and enzyme-linked immunosorbent assay samples. PMID- 7785782 TI - Simultaneous determination of enzyme activity and enzyme quantity in single human erythrocytes. AB - An integrated laser-based fluorescence enzyme assay and particle-counting immunoassay system with zeptomole sensitivity has been developed for simultaneous determinations of activity and concentration of enzymes in single erythrocytes. The product NADPH of the reaction between glucose-6-phosphate and NADP+ catalyzed by glucose-6-phosphate dehydrogenase (G6PDH) is monitored. Simultaneously, the agglutination of antibody-coated particles in the presence of G6PDH produces large particles which are counted by light scattering. The correlation between the two parameters indicates that on average only about 35% of the enzyme in individual cells is active. There is more than a 10-fold cell-to-cell variation in the ratios of the two parameters. This indicates that there are multiple mechanisms for the degradation of intracellular enzymes as a function of cell age. PMID- 7785783 TI - A quantitative test for copper using bicinchoninic acid. AB - We describe a direct colorimetric assay for copper in serum and biological samples using 2,2'-bicinchoninic acid (BCA), a common reagent in most laboratories. BCA offers the advantage of being highly sensitive and specific for Cu(I) which rapidly forms an intense purple complex in the presence of BCA. The complex has peak absorbances at 562 and 354.5 nm with molar absorptivities of 7.7 x 10(3) liter mol-1 cm-1 and 4.6 x 10(4) liter mol-1 cm-1, respectively. Interference by other metal ions, pH, and detergents is minimal and the results correlate strongly with atomic absorption spectrophotometry. PMID- 7785784 TI - A microtiter plate-based high-throughput DNA purification method. AB - A fast, reliable, inexpensive, and high-throughput method to purify DNA has been developed. It is based on DNA amplification by polymerase chain reaction utilizing a mini spin-column made from a 96-well membrane-bottomed assay plate. With this method, 50% of the DNA is recovered routinely using Sephacryl-500HR as filtration media. Purified DNA can then be used in various enzymatic manipulations, such as sequencing and hybridization. This provides an economical alternative protocol for routine large-scale purification of DNA templates for sequencing or other enzymatic manipulations. PMID- 7785785 TI - Isolation of pure populations of epithelial and myoepithelial cells from the normal human mammary gland using immunomagnetic separation with Dynabeads. AB - Monoclonal antibodies to epithelial membrane antigen and common acute lymphoblastic leukemia antigen were bound to second antibody-coated magnetic microspheres. These specific antibody/bead complexes were then used to directly isolate purified epithelial and myoepithelial cells from normal breast organoid cell preparations by magnetic separation. Near homogeneous cell populations were selected with yields of 10-20 x 10(6) epithelial and myoepithelial cells per organoid preparation. Repeated purification steps allowed almost complete depletion of myoepithelial cells for RNA studies. Tissue culture of separated cell populations in appropriate defined media further ensured purity of cell type and was unimpeded by Dynabead attachment. PMID- 7785786 TI - Contraction of isolated porcine coronary arteries is inhibited by high concentrations of propranolol. AB - Isometric tension responses of isolated porcine coronary artery rings were studied in the presence of concentrations of propranolol higher than those necessary to block effects mediated by beta-adrenergic receptors. Propranolol (50 300 microM) inhibited contractions induced by 30 mM KCl and by histamine, norepinephrine, and acetylcholine in a concentration-dependent, noncompetitive fashion. The (+) propranolol isomer and the racemic mixture were equipotent inhibitors of contraction. Propranolol inhibition was partly reversed by increased extracellular Ca++. These effects of propranolol thus appeared to be independent of beta-blockade and could be relevant to some of the drug's observed but still unexplained in vivo actions. PMID- 7785787 TI - Combined left ventricular wall motion and myocardial perfusion stress imaging in the initial assessment of patients with a recent uncomplicated myocardial infarction. AB - The aim of the study was to examine the ability to simultaneously assess left ventricular function and myocardial perfusion by using a single injection of technetium-99m sestamibi at rest and during submaximal exercise to identify high risk patients with left main, proximal left anterior descending (LAD), or three vessel coronary artery disease (CAD) after an uncomplicated acute myocardial infarction (AMI). Multiple studies have evaluated the separate value of the exercise ECG, myocardial perfusion scintigraphy, and radionuclide angiocardiography (RNA) for identifying patients with severe CAD. The availability of technetium-99m (Tc99m)-labeled myocardial imaging agents offers the opportunity to evaluate simultaneously ventricular function and myocardial perfusion during a single exercise session. Only limited data are available about the value of this combined technique in the workout of patients early after an uncomplicated AMI. Combined first-pass RNA and myocardial perfusion tomoscintigraphy (SPECT) at rest and during submaximal exercise were performed in 52 patients, less than six weeks after an uncomplicated AMI, with use of Tc99m sestamibi. Patients were classified in two subgroups according to the presence of left main, proximal LAD, or three-vessel CAD. Stepwise logistic regression analysis was used to determine the independent predictors of severe CAD. All patients underwent the exercise testing without any medical complication. On univariate analysis, the global left ventricular ejection fraction (LVEF), wall motion score, and myocardial perfusion score, both at rest and at submaximal exercise, were significantly associated with the presence of severe CAD. The response of LVEF to exercise, and the presence of exercise-induced wall motion or myocardial perfusion abnormalities, were not associated with the severity of CAD. On multivariant analysis only the wall motion score during exercise was an independent predictor for the presence of severe CAD (P < 0.001, r = 0.6). In analyzing patients with anterior AMI separately, LVEF at submaximal exercise was the most accurate predictive parameter. If a cutoff value of 40% was chosen, the LVEF at exercise had a sensitivity of 85% and a specificity of 78% for the detection of severe CAD. In patients with inferior AMI, neither LVEF nor wall motion or myocardial perfusion scores were useful for differentiating the two subgroups. In these patients the presence of an additional perfusion defect during exercise in one of the anterior wall segments yielded a sensitivity of 70% and a specificity of 75% for the presence of severe CAD. IN CONCLUSION: simultaneous evaluation of LV function and myocardial perfusion at submaximal exercise, using a single injection of Tc99m-sestamibi, is a safe and accurate technique for selecting patients with severe CAD after an uncomplicated AMI. PMID- 7785788 TI - Brain infarction developed in hypertensive and normotensive patients during hospitalization--hemodynamic factors. AB - To determine the effects of changes in blood pressure (BP) on the development of ischemic stroke, 17 patients who developed acute brain infarction during hospitalization were analyzed in relation to the vascular risk factors such as hypertension, previous stroke, diabetes mellitus, and hyperlipidemia. Their BPs were retrospectively referred to the onset of stroke. The average values of mean arterial blood pressure (MABP) on admission were 137 mmHg in hypertensive patients (HT; n = 9) and 101 mmHg in normotensives (NT; n = 8). HT patients received antihypertensive treatment after admission and MABP decreased by 22 mmHg (14%) prior to the ictus (three to sixty-five days after admission). MABP in NT patients remained constant before the attack (-1.4 mmHg, four to one hundred ten days after admission). Similarly, MABP decreased by 17 mmHg (four to ninety-three days) before the ictus in patients with previous stroke (n = 9), whereas it changed only a little in patients without history of stroke (n = 8). BP in each group elevated immediately after the stroke and gradually decreased to 90% of the resting level after two weeks. An excessive reduction of BP may induce brain infarction in HT or chronic stroke patients or cause it to recur. PMID- 7785790 TI - Relation between postpacing T wave changes and myocardial scintigraphic characteristics in patients with ventricular demand pacemaker. AB - The aim of this study was to elucidate the cause of T wave changes after ventricular pacing using thallium 201 single photon emission computed tomography (Tl-SPECT). Tl-SPECT was performed in 20 patients with sick sinus syndrome who had negative T wave after ventricular pacing and had had a ventricular demand pacemaker (VVI) implanted. Patients who have stenotic coronary arteries were excluded from the study. From the analysis of Tl-SPECT, extent score was calculated as the ischemic region. Data in patients with SSS were compared with those in 20 normal controls (NC). Thallium perfusion defects in patients with VVI were observed and distributed mainly in apex and inferior regions on the polar map. The extent score in patients with VVI was significantly higher than that in NC (56.4 +/- 21.6% vs 3.2 +/- 6.4%, P < 0.01). The washout rate of thallium 201 in the defect area was significantly lower in patients with VVI than in NC (27.4 +/- 10.2% vs 46.8 +/- 12.3%, P < 0.01). These results suggest that T wave changes after ventricular pacing are closely related to myocardial ischemia. PMID- 7785789 TI - In vivo measurement of regional large artery compliance by intravascular ultrasound under pentobarbital anesthesia. AB - BACKGROUND: The presence of smooth muscle fibers on the wall of large arteries would suggest that arterial compliance might change in response to vasoactive substances. The purpose of this study is to determine the basal level of vasomotor tone in these arteries in a commonly used animal preparation and to learn whether the compliance of large conductance arteries can be altered in vivo by vasoactive agents. METHODS: Proximal iliac arterial compliance was measured in 7 pentobarbital-anesthetized pigs, before and during local infusions of adenosine and norepinephrine. Luminal area was measured every forty milliseconds by means of a 30 MHz intravascular ultrasound catheter and an automatic edge detection program. Simultaneous high-fidelity pressure measurements were obtained by means of a catheter-tipped pressure microtransducer positioned at the origin of the iliac artery. Linear regression analysis of the area/pressure relationship in two consecutive cardiac cycles (systolic phase only) was performed before and during adenosine and norepinephrine infusions. The slope of the area/pressure regression line was defined as an index of arterial compliance. Measurements after three minutes of infusions of adenosine (5-5000 micrograms/minute) and norepinephrine (0.001-10 micrograms/minute) were compared with the control measurements. RESULTS: Even at the highest infusion rate, adenosine did not significantly increase arterial compliance as compared with baseline (25 +/- 7 vs 19 +/- 4 mm2/mmHg x 10(-3), respectively, P = ns). In contrast, norepinephrine decreased arterial compliance as compared with the second baseline control (13 +/- 3 vs 20 +/- 3 mm2/mmHg x 10(-3), respectively, P < 0.01). CONCLUSIONS: In this animal model with pentobarbital anesthesia, arterial compliance may be modified more by the acute infusion of norepinephrine than by adenosine in large conductance arteries such as the proximal iliac. Thus, in this preparation, smooth muscle tone tends to be minimal and arterial compliance near maximal (ie, mostly a passive phenomenon). However, in response to norepinephrine, arterial compliance can decrease significantly as smooth muscle tone increases. Intravascular ultrasound allows continuous and accurate monitoring of these changes of arterial dimensions, suggesting that this technique may be useful in the evaluation of pharmacologically induced changes in the compliance of large arteries by vasoactive agents. PMID- 7785791 TI - Unstable angina of crescendo pattern vs new onset: a clinical, coronary arteriographic and hemodynamic study. AB - Unstable angina includes a variety of clinical presentations with a different level of risk for an unfavorable outcome. In this study the authors investigated the prognostic significance of crescendo angina and new-onset angina to discuss management strategies, paying attention to the relevance of baseline clinical characteristics, coronary artery lesions, and left ventricular function, as well as their alterations during atrial pacing. Accordingly coronary arteriographic anatomy and changes in left ventricular volumes and ejection fraction before and during atrial pacing were studied by means of digital subtraction ventriculography in 18 patients with crescendo angina and in 18 patients with new onset angina. Triple-vessel disease was more frequently observed in crescendo angina (56%; P < 0.05) as compared with the patients with new-onset angina (11%). Complex coronary morphology was statistically more likely to be found in crescendo angina. The angiographic evidence of intracoronary thrombi was found in 33% (P < 0.05) patients with crescendo angina and in 4% patients with new-onset angina. Compared with the patients with new-onset angina, patients with crescendo angina had higher end-diastolic and end-systolic volumes and lower ejection fraction at rest. At peak pacing, ejection fraction was significantly (P < 0.05) lower in crescendo angina (0.48 +/- 0.06) than in new-onset angina (0.66 +/- 0.04). In crescendo angina, during pacing, the magnitude of velocity of circumferential fiber shortening was significantly decreased as compared with new onset angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785792 TI - Percutaneous balloon valvuloplasty in severe pulmonary valvular stenosis. AB - Percutaneous balloon pulmonary valvuloplasty (PBPV) was achieved successfully in 20 of 22 patients with severe pulmonary valvular stenosis, aged two days to ten years (median four years and two months). The diameters of the balloon for PBPV were 88-125% (mean +/- SD = 109.5 +/- 10.0%) of the pulmonary valve annulus. PBPV failed in 2 patients because of the inability of the cardiac catheters to cross the stenotic valve. A significant reduction of right ventricle-pulmonary artery (RV-PA) pressure gradient occurred in all 20 patients (mean +/- SD = 72.1 +/- 10.3%). The mean RV-PA pressure gradient was reduced from 93.2 +/- 33.1 to 26.3 +/- 15.6 mmHg (P < 0.0001) and the mean right ventricular peak systolic pressure fell from 117.2 +/- 32.4 to 51.6 +/- 17.3 mmHg (P < 0.0001). Five (25%) of 20 patients had an infundibular gradient before PBPV. Two (10%) developed a new infundibular stenosis immediately after PBPV. Four (20%) presented with cyanosis, which disappeared after the successful PBPV. Two patients (10%) who showed a residual RV-PA pressure gradient of more than 40 mmHg had a significant infundibular obstruction initially. Two patients underwent recatheterization fifteen months after PBPV owing to a significant residual RV-PA pressure gradient and had no reductions in right ventricular pressure and RV-PA pressure gradient, but resolution of infundibular obstruction was noted in both. Repeat PBPV was successfully performed on these 2 patients. No significant complications were noted in any patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785793 TI - Atrial natriuretic peptide and antihypertensive action due to beta-blockade in essential hypertensive patients. AB - The effects of beta-blocker treatment on hemodynamics were studied in relation to plasma atrial natriuretic peptide (ANP) levels in 17 outpatients with essential hypertension. Administration of propranolol for twelve weeks to untreated subjects resulted in a significant (P < 0.001) rise in plasma ANP levels (from 37.9 +/- 21.2 to 66.7 +/- 46.2 pg/mL, mean +/- SD). Systolic and diastolic blood pressures were significantly decreased (P < 0.05 and P < 0.01, respectively). Heart rate was also significantly decreased (P < 0.001). On the other hand, a significant reduction of cardiac index was detected (from 4.12 +/- 1.34 to 2.96 +/- 0.75 L/min/m2, P < 0.01) with chronic administration of propranolol, suggesting a reflection of decreased cardiac function. A significant negative correlation was observed between %changes in systolic blood pressure and %changes in plasma ANP (r = -0.594, P < 0.05). These results suggest that the increased plasma ANP levels may contribute to the antihypertensive effect with propranolol. PMID- 7785794 TI - Refractory cardiogenic shock and complete heart block after verapamil SR and metoprolol treatment. A case report. AB - A seventy-eight-year-old woman presented with complete heart block and refractory hypotension two days after a therapeutic dose of sustained-release verapamil with concomitant use of metoprolol. The patient continued to remain hypotensive with complete heart block, even with multiple uses of intravenous atropine as well as high doses of pressor agents such as dopamine and dobutamine. However, shortly after the use of intravenous calcium chloride, the refractory hypotension and complete heart block resolved. PMID- 7785795 TI - Acute myocardial infarction shortly after a normal exercise stress test. Case reports. AB - The authors describe 3 cases of AMI occurring shortly after a negative bicycle ergometer stress test. These cases represent an unfortunate but extremely rare complication of a relatively safe diagnostic procedure. The authors also focus on the pathogenesis of the ischemic event, which may be attributed either to intraplaque hemorrhage or to platelet aggregation, both exercise-induced. The prevalence of AMI in this paper (0.06%) is similar to the data described in literature. PMID- 7785796 TI - Myocardial infarction secondary to coronary aneurysm in systemic lupus erythematosus. An autopsy case. AB - The authors report a thirty-seven-year-old woman with systemic lupus erythematosus (SLE), a coronary aneurysm, and myocardial infarction. SLE was diagnosed at twenty-three years of age and treated with prednisolone. Seven years later, she developed inferior myocardial infarction, and coronary angiography showed an aneurysm in the proximal right coronary artery without associated stenosis. At the age of thirty-seven years, she died from cerebral infarction and sepsis. Autopsy revealed an aneurysm (6 mm in diameter) in the proximal right coronary artery and an old inferior myocardial infarction. Histologic examination showed recanalization and fibrosis in the media of the aneurysm wall. This case suggests that coronary aneurysm may cause myocardial infarction in SLE and that aneurysm formation may be a sequela of arteritis. PMID- 7785797 TI - Transesophageal echocardiography combined with magnetic resonance imaging for detecting venous anomalies in dextrocardia. A case report. AB - A fifty-six-year-old woman was admitted to Osaka Rosai hospital because of dyspnea, chills, and fatigue. The patient was diagnosed by transthoracic echocardiography as having congestive heart failure due to severe biatrioventricular valve regurgitation, and cardiac surgery was proposed. Preoperative transesophageal echocardiography (TEE) revealed a dilatation of the coronary sinus (CS), a right-sided hemiazygos vein (R-AZ), and another great vessel lying between the CS and the R-AZ. Magnetic resonance imaging (MRI) was also performed, and this showed a persistent right superior vena cava (PRSVC) entering the left atrium via the dilatated CS. However, the site of connection between the R-AZ and the PRSVC could not be detected by MRI because of inadequate slice acquisition. Each method has its limitations, particularly with regard to visualizing the extracardiac vascular system. Therefore, the authors demonstrated that the combination of TEE and MRI might be more useful than each alone, and the combination is as a valuable method as digital subtraction angiography for the diagnosis of extracardiac venous anomalies. PMID- 7785798 TI - Heart block in dextrocardia with situs inversus. A case report. AB - The authors report a case of a forty-one-year-old white woman with dextrocardia with situs inversus who presented episodes of prolonged sinus arrest and syncopal episodes secondary to possible idiopathic degeneration of the conduction system, managed successfully with a permanent bicameral pacemaker. In their literature review they found that this case represents a very rare association. PMID- 7785799 TI - Cerebral dural sinus thrombosis. A case report. AB - Cerebral dural sinus thrombosis is an uncommon syndrome that a patient presents with severe headache, which may be associated with complex physical and neurologic findings. The authors present a thirty-two-year-old woman with severe headache, focal motor seizures, and subsequent hemiparesis when she was ten weeks pregnant, diagnosed as having a dural sinus thrombosis by magnetic resonance imaging and magnetic resonance angiography. In this report, the application of magnetic resonance techniques, including angiography to diagnose and monitor therapy for dural sinus thrombosis, is presented. PMID- 7785800 TI - Enamel surfaces after orthodontic bracket debonding. AB - The enamel surfaces of extracted teeth were studied clinically and with a scanning electron microscope following debonding of orthodontic attachments and subsequent polishing. Excess orthodontic resin was removed with tungsten carbide burs and abrasive discs. Several combinations of polishing agents were evaluated. The no. 30 fluted tungsten carbide bur appeared to be the most efficient method of removing highly filled resin, and it produced the least amount of scarring. A polishing sequence was developed which used resin points and cups followed by a water slurry of fine pumice and brown and green cups. This procedure was tested clinically and appeared to return the enamel to an acceptable condition. This procedure is fast, efficient, and comfortable for the patient. PMID- 7785801 TI - In vitro release of nickel and chromium from different types of simulated orthodontic appliances. AB - Five identical samples, each consisting of a fixed appliance, a headgear and a quad-helix for one-half of a dental arch, were immersed in 0.9% sodium chloride for 2 hours, 24 hours and 7 days. A control appliance was subjected to dynamic test conditions in a specially built "oral simulator" under similar test conditions. A significant release of nickel was detected from the quad-helix during the first two hours in static conditions, whereas during the following two periods significantly less nickel was released from the quad-helix than from the other appliances. The fixed appliance with simulated function showed a significantly higher cumulative release of nickel than the similar appliance in static conditions, 44.2 micrograms (SD 22.8) and 17.1 micrograms (SD 3.4). The total amounts of chromium released from the fixed appliance were significantly lower than those of nickel. No difference in the release of chromium was seen between the static and dynamic conditions. The results indicate certain differences in the amount and pattern of nickel release from different stainless steel orthodontic appliances in vitro. The release rate of nickel from dynamically loaded fixed appliances was found to be accelerated compared with that released under static conditions. Caution should be exercised when applying the results to the in vivo situation. PMID- 7785802 TI - Comparisons of the thermodynamic properties of three nickel-titanium orthodontic archwires. AB - The unique memory property of thermodynamic wire is only partially understood. It is believed to result from the wire's inherent capability to markedly alter its atomic bonding forces as a function of temperature. This shape recovery phenomenon may be the result of a transition in crystal structure that occurs by deformation and cooling. When the transition is reversed, by heating, the structure reverts to its original form and abrupt property changes occur. The purpose of this study was to determine the transition temperature ranges (TTR) of three commercially available thermodynamic archwires and to determine the rate of recovery of the wires when bent to a uniform shape. A jig was constructed to hold the wires and was suspended in a water bath within a plexiglass box. The temperature of the water bath was gradually increased. A program was written to acquire a single video frame from a running video tape and then allow the operator to graphically overlay the position of each wire specimen. The results indicate that the TTRs for the three commercially available thermodynamic wires are of similar magnitudes (x = 6.7 degrees C, 6.2 degrees C and 6.7 degrees C). The greatest differences were in the standard deviations (1.3 degrees C, 2.2 degrees C and 3.7 degrees C) which may be a function of manufacturing during alloying of the wire and/or its heat treatment. PMID- 7785803 TI - Biomechanical behavior of the periodontium before and after orthodontic tooth movement. AB - This study was designed to investigate the biomechanical behavior of the periodontium including the periodontal ligament (PDL) in terms of tooth mobility. Tooth mobility was measured in the canines of 10 adolescent patients before and after distal movement. Distal movement of the canines was carried out by use of a calibrated sectional archwire exerting an initial retraction force of 200 g. Tooth mobility was measured immediately before and after canine retraction by use of a noncontact displacement sensor when varying distal forces of 0 to 500 g were applied to the mesial of the canine. Before tooth movement, tooth mobility exhibited a substantial increase in loading with forces ranging from 50 to 150 g. The rate of increase gradually decreased up to 500 g. A nonlinear change in tooth mobility was similarly observed at the end of tooth movement or 24 days after the initiation of movement. Tooth mobility, however, was significantly greater when forces above 200 g were loaded. The periodontal tissues--the PDL and alveolar bone in particular--become more flexible at the end of tooth movement, indicating reduced support by the periodontal tissues. These findings suggest that the elastic nature of the PDL and alveolar bone may decrease substantially at the end of tooth movement. PMID- 7785804 TI - Orthodontic bone remodeling in relation to appliance decay. AB - This study examined alveolar bone turnover and orthodontic tooth movement after appliance decay. One group of rats (N = 54) received orthodontic force (40 g initial activation) while the other (N = 36) was sham-treated. Groups of six rats were sacrificed at various times following activation. Tooth movement and appliance decay were monitored cephalometrically, and bone turnover was monitored locally by histomorphometry and phosphatase chemistries and systemically by serum phosphatase and osteocalcin changes. A significant association was found between spring forces assessed by direct measurement and by cephalometric images (R2 = 0.784; p = 0.02). The cephalometric method indicated appliances were at least 93% deactivated by day 16. Tooth movement continued beyond the point of appliance decay (p < 0.001). This was accompanied by a dramatic decline in osteoblast surface (p < 0.0001) and an increase in osteoclast surface to control levels (p < 0.001). A significant peak in bone formation rate was also noted around appliance decay (p = 0.005). Serum acid phosphatase and osteocalcin also increased after appliance decay (p < 0.05), but alkaline phosphatase did not. Bone acid phosphatase was characterized by a peak after appliance decay (p = 0.0004), but alkaline phosphatase remained depressed (p < 0.0001). These data demonstrate that significant amounts of alveolar bone turnover continue for an indeterminant period following appliance decay. PMID- 7785805 TI - Remodeling mechanisms of transseptal fibers during and after tooth movement. AB - The remodeling mechanisms of transseptal fibers during and after tooth movement were investigated histologically. An autoradiographic study was conducted to assess the synthetic response. One hundred fifty male Wistar strain growing rats were divided into three groups--one control and two experimental groups. Animals in the experimental groups were subjected to tooth movement with 25 g and 150 g of force. Maxillary first and second molars were separated and retained mechanically. Transseptal fibers were stretched in proportion to the amount of force applied for up to 2 days. Dynamic remodeling with proliferation of fibroblasts during tooth movement and slow rearrangement during retention periods occurred in both experimental groups. Collagen phagocytosis within the fibroblasts was observed ultrastructurally during the experimental periods. The number of silver grains in fibroblasts in the collagen fibers increased 160% the first day and 206% during the first 3 days. Proliferating fibroblasts remodeled the transseptal fibers through the synthesization and degradation of collagen fibers. PMID- 7785806 TI - Statistical analysis of differential lissajous EMG from normal occlusion and Class III malocclusion. AB - The method of differential lissajous electromyography (DL-EMG) was applied to investigate the relationship among the integrated EMG activity, timing, and coordination of the bilateral superficial anterior temporal and masseter muscle activities in normal occlusion and Class III malocclusion subjects. In both Class III malocclusion and normal occlusion subjects, the working side muscles showed a higher mean cumulative voltage (MCV) and mean maximum peak voltage (MMPV) compared with the balancing side. In addition, a higher MCV and MMPV of the working side masseter was observed in the normal occlusion group compared with that seen in the Class III group during both right and left side chewing (p < 0.01). Discriminant analysis applied to examine the distribution, the size and the shape of DL-EMG pattern further indicated a statistical difference between subject groups (p < 0.01). Finally, there was a significantly higher percentage of clockwise DL-EMG pattern-generation in the normal group compared with that seen for Class III subjects (p < 0.01). These data indicate that, compared with normal subjects, patients with a Class III malocclusion have a demonstrably abnormal masticatory muscle balance which is well characterized by the DL-EMG method. PMID- 7785807 TI - The return of tooth surface luster following bracket removal. PMID- 7785808 TI - Crowding: timing of treatment. PMID- 7785809 TI - Extraction frequencies. PMID- 7785810 TI - Case report MH. Class II, Division 1 malocclusion with anterior openbite. AB - This case report was presented at a regular meeting of the Southern California Component of the Edward H. Angle Society in 1994. It demonstrates the value of two-phase treatment which resulted in effective vertical control. PMID- 7785811 TI - In defense of the guidance theory of palatal canine displacement. AB - From the foregoing debate it will be quite clear that Peck et al. have provided ample evidence that may be used to fuel the arguments of both sides: 1. Their material does not contradict the possibility that environmental factors may give rise to palatal displacement of canines generated by genetic anomaly of the adjacent teeth. 2. The buccally displaced canine finds itself similarly environmentally compromised by the different factor of crowding which leads to its characteristic buccally ectopic guidance pattern. 3. (a) Canines that are transposed with the premolar, (b) others that have erupted ectopically, high in the buccal sulcus and in the absence of crowding, and (c) certain palatal canines whose root apex is located markedly distant from their designated site, may all be labeled as genetically controlled with a fair degree of confidence. 4. In between these clearly defined entities there exists a "gray area" in which it is probable that the etiology of the individual displaced teeth may be linked to a combination of circumstances that obey premise number 1 and premise number 2, to varying degrees. The guidance theory cannot provide the complete answer to the etiology of the palatally displaced canine. Were this so, we would find PDC every time there was an anomalous or missing lateral incisor. Equally, it may not yet be discounted out of hand and certainly not on the basis of the evidence provided in the article in question. PMID- 7785812 TI - Enzyme-linked immunosorbent assay for apolipoprotein A-I in the serum of cattle. AB - An ELISA was developed to evaluate the concentration of apolipoprotein A-I, a major apoprotein in high-density lipoprotein, in the serum of cattle. Serum apolipoprotein A-I was purified electrophoretically, and antibodies to this protein were raised in rabbits. The specificity of the antiserum was assessed by use of several immunologic techniques including western blotting. The ELISA was sensitive (detection limit was 70 ng of apolipoprotein A-I/ml) and reliable (coefficients of variance were in the range of 3.5 to 8.2%). By use of this method, the serum apolipoprotein A-I concentration was higher in 2- to 6-year-old Holstein cows (mean +/- SD, 0.580 +/- 0.304 mg/ml) than in 7- to 15-month-old heifers (0.339 +/- 0.237 mg/ml), 6-month-old heifers (0.238 +/- 0.188 mg/ml), and 6-month-old steers (0.173 +/- 0.146 mg/ml). The concentration, however, is not largely different in cows in early, middle, and late lactation and in non lactating stages. Results also indicated that apolipoprotein A-I concentration was decreased in cows with hepatic lipidosis (fatty liver) induced by administration of ethionine, suggesting that this method is a useful tool for the pathophysiologic study of lipid metabolism and its impairment in cattle. PMID- 7785814 TI - Body weight, heart weight, and heart-to-body weight ratio in greyhounds. AB - Heart and body weights were obtained from 230 Greyhounds during necropsy. Sex and age were recorded for each Greyhound. Twenty-nine racing and 21 nonracing Greyhounds among the 230 dogs were compared. Heart-to-body weight ratio was calculated. Statistical analysis was done to determine the effects of age, sex, and racing on heart and body weights and heart-to-body weight ratio. In adult Greyhounds, mean +/- SD body weight was 28.4 +/- 3.1 and 31.5 +/- 2.8 kg, heart weight was 355.6 +/- 52.8 and 381.4 +/- 50.8 g, and heart-to-body weight ratio was 1.3 +/- 0.2 and 1.2 +/- 0.2% for females and males, respectively. Heart and body weights were significantly different between sex and age groups and among nonracing and racing males. However, heart-to-body weight ratio was not significantly different among age, sex, or racing groups. PMID- 7785813 TI - Comparison of the sensitivity of the caudal fold skin test and a commercial gamma interferon assay for diagnosis of bovine tuberculosis. AB - A study to determine and compare the sensitivity of the caudal fold tuberculin test (CFT) and a commercial gamma-interferon (gamma-IFN) assay for diagnosis of bovine tuberculosis was conducted. A dairy herd with approximately a third of the cattle infected with Mycobacterium bovis was chosen for this study. All cattle from this herd were slaughtered, and tissue specimens for bacteriologic culturing and histologic examination were collected. Results of the CFT and gamma-IFN assay were compared with results of bacteriologic culturing and histologic examination to determine test sensitivity. Results were analyzed, using each of the following 4 standards to classify cattle as infected: positive test result by bacteriologic culturing only; histologic examination only; bacteriologic culturing and histologic examination; and bacteriologic culturing or histologic examination. Sensitivity of the CFT ranged from 80.4 to 84.4%, depending on the standard of comparison. Sensitivity of the gamma-IFN assay ranged from 55.4 to 97.1%, depending on the standard of comparison and on the method of interpretation. The CFT was significantly (P < 0.001) more sensitive than the gamma-IFN assay for diagnosis of bovine tuberculosis when the gamma-IFN assay was conducted and interpreted as instructed by the manufacturer. Maximum overall sensitivity was achieved when results of the CFT and gamma-IFN assay were interpreted in parallel. PMID- 7785815 TI - Tissue and serum enzyme activities in the yellow rat snake (Elaphe obsoleta quadrivitatta). AB - Activities of diagnostically important enzymes were measured in serum and lysates of liver, kidney, skeletal muscle, heart, intestine, lung, and pancreatic tissues from wild-caught yellow rat snakes, Elaphe obsoleta quadrivitatta. All samples were analyzed for alkaline phosphatase, lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase, gamma-glutamyltransferase, and creatine kinase (CK) activities. The major enzyme activities found in the liver were LD and AST. The kidney had moderate activities of LD, AST, alanine transaminase, and CK. Skeletal muscle and heart contained high CK activity. Intestine, lung, and pancreas had low activities for most enzymes analyzed. Little to no gamma glutamyltransferase activity was found in serum or tissues analyzed. Serum enzyme activities in yellow rat snakes were similar to those described for other reptile species, except for serum CK activity, which was increased in rat snakes. PMID- 7785816 TI - Risk of feline infectious peritonitis in cats naturally infected with feline coronavirus. AB - A longitudinal survey of 820 cats in 73 households was conducted over a period of 6 years to establish the fate of pet cats that were seropositive after natural exposure to feline coronavirus (FCoV). In particular, their risk of developing feline infectious peritonitis (FIP) was determined. The seropositive cats were assigned to 1 of 3 groups: cats from households in which FIP had recently been diagnosed; cats from households in which FIP had not been diagnosed, but from which kittens had been relocated and subsequently died of FIP; and cats from households in which FIP had not been diagnosed. Cats in the first group were not at greater risk of developing FIP than were cats in the other 2 groups. Consequently, any household in which seropositive cats live must be considered a potential source of FCoV that can cause FIP. There was no evidence that the enhanced disease, which has been described after experimentally induced infection of seropositive cats, exists in nature. Thus, analysis of the survival of the seropositive cats over periods of up to 36 months indicated that their risk of developing FIP decreased with time, suggesting the development of immunity rather than increased susceptibility to disease. In addition, of 56 cats deemed to have been naturally reinfected because their anti-FCoV antibody titers decreased and subsequently increased, only 3 developed FIP. PMID- 7785817 TI - Complement component C3b and immunoglobulin Fc receptors on neutrophils from calves with leukocyte adhesion deficiency. AB - Receptors for opsonins, such as complement component C3b (CR1) and immunoglobulins, Fc receptors, interact with adhesion glycoproteins in mediating immune functions. Defects in expression of the adhesion glycoproteins CD11/CD18 results in severely hampered in vitro and in vivo adherence-related functions of leukocytes. Little is known regarding the effect of leukocyte adhesion deficiency (LAD) on ligand binding and receptor expression. We investigated the binding and expression of CR1 and Fc receptors by bovine neutrophils isolated from dairy calves suffering from LAD, compared with clinically normal (hereafter referred to as normal) age-matched calves. Neutrophils were also assayed for endogenously bound IgG and IgM and for exogenous binding of C3b, IgG1, IgG2, IgM, and aggregated IgG (aIgG), using flow cytometry. Luminol-enhanced chemiluminescence (CL) production in response to IgG2 opsonized zymosan was studied, and specific inhibition of CL was used to determine the specificity of IgG2 binding. Activation of protein kinase C with phorbol myristate acetate was used to determine the effect of cellular activation on expression of CR1. A greater percentage of neutrophils from normal calves bound C3b than did neutrophils from LAD-affected calves. Receptor expression was similar. Activation with phorbol myristate acetate resulted in increased expression of CR1 on neutrophils from normal and LAD-affected calves, but expression was almost twofold greater on neutrophils from normal calves. There was no difference between LAD-affected and normal calves in percentage of neutrophils that bound endogenous IgG and IgM. A greater percentage of neutrophils from normal calves bound exogenous IgM than did neutrophils from LAD-affected calves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785818 TI - Use of predictive modeling to evaluate the manipulation of milking frequency, temperature, and oxygen tension on growth of Escherichia coli in an artificial intramammary environment. AB - A method was developed to evaluate frequent milking as a means of controlling intramammary infection. An artificial intramammary environment was used to determine growth responses of Escherichia coli (P4) to natural changes in the mammary gland resulting from bacterial invasion. Physical conditions manipulated in this model were growth medium, temperature, and oxygen tension. Mathematical modeling was then incorporated to generate predictions concerning growth dynamics of the organism when milking frequency was changed. To test accuracy of the model, initial predictions were derived from bacterial growth data in which E coli was incubated in tryptose soy broth for 12 hours at 37 C and PO2 equal to 23.3 mm of Hg. These predictions matched closely with experimental data in which 12-, 4-, and 2-hour milking intervals were simulated in the artificial intramammary environment. The mathematical model was then used to characterize growth rate data from in vitro experiments in ultra-high temperature-treated milk and in vivo experimental infection data generated with E coli (P4). Predictions generated from this model suggested that increasing milking frequency to 4 or 6 times daily controls growth of E coli for a prolonged period and that 12 times daily milking may lead to elimination of the bacterium. PMID- 7785819 TI - Detection of bovine immunodeficiency virus in blood and milk-derived leukocytes by use of polymerase chain reaction. AB - Bovine immunodeficiency virus (BIV) is prevalent in beef and dairy cattle, yet the mode(s) of BIV transmission are undefined. Using polymerase chain reaction, which specifically targeted a 235-bp, highly conserved region of the BIV pol gene, BIV-infected leukocytes were detected in the blood and milk of BIV seropositive cows. These data confirm the presence of BIV in milk and identify the potential for lactogenic transmission of this virus. PMID- 7785820 TI - Effect of selenium supplementation on colostral IgG concentration in cows grazing selenium-deficient pastures and on postsuckle serum IgG concentration in their calves. AB - Effects of selenium (Se) deficiency and supplementation on production of colostral immunoglobulins by beef cows and transfer of antigen-specific and nonspecific immunoglobulins to their calves were examined. Eight beef cows, with marginal to deficient Se status (blood Se concentration, 50 micrograms/L), were allotted by breed and age to 1 of 4 Se treatment groups (n = 20/group): no supplemental Se; parenteral administration of 0.1 mg of Se and 1 mg of vitamin E/kg of body weight; ad libitum consumption of 120 mg of Se/kg of salt-mineral mix (SMM); and parenteral administration of 0.1 mg of Se and 1 mg of vitamin E/kg plus ad libitum consumption of 120 mg of Se/kg of SMM. All cows were inoculated IM with lysozyme. Cows consumed Se-deficient pastures or hay (21 to 62 micrograms/kg) during the study that began at mid-gestation and ended at postpartum hour 24. Although the concentration of specific lysozyme antibodies was not affected, cows given 120 mg of Se/kg of SMM (treatments 3 and 4) had higher colostral IgG concentration (P < 0.002) than did Se-deficient cows (treatments 1 and 2). Calves from cows in treatments 3 and 4 had higher postsuckle serum concentrations of IgG (P < 0.01) than did calves from cows in treatments 1 and 2. Colostral IgM and calf serum IgM concentrations did not differ among treatments. PMID- 7785821 TI - Specific antibodies in serum and vaginal mucus of heifers inoculated with a vaccine containing Tritrichomonas foetus. AB - Thirty-five heifers were allotted to 3 groups. Group 1 (control) consisted of 10 heifers that were not vaccinated and were challenge exposed by breeding to infected bulls. Group 2 (natural challenge exposure) consisted of 10 heifers that were vaccinated and challenge exposed by breeding to infected bulls. Group 3 (experimental challenge exposure) consisted of 15 heifers that were vaccinated and challenge exposed by breeding to infected bulls and by intravaginal inoculation with 10(7) Tritrichomonas foetus. Total immunoglobulin concentrations and specific trichomonal antibodies were determined in serum and vaginal secretions of heifers, using radial immunodiffusion and ELISA procedures. Control heifers remained infected for a mean of 10.6 weeks (range, 0 to 18 weeks), and heifers of the natural and experimental challenge-exposure groups remained infected for 3.2 and 5.0 weeks, respectively (range, 0 to 12 weeks). Total serum and cervicovaginal mucus concentrations of IgM, IgA, IgG1, and IgG2 did not change significantly after vaccination or challenge exposure. However, ELISA titers of total trichomonal antibodies increased up to 1:10,000 (range, 1:400 to 1:10,000) in serum after vaccination, and increased approximately tenfold above background in cervicovaginal mucus. In serum, the predominant trichomonal antibody isotype was IgG1, although trichomonal IgA and IgM antibodies also increased. The predominant trichomonal antibody detected in cervicovaginal mucus was IgA. Antibody titers in serum and cervicovaginal mucus of vaccinated heifers were not increased by infection. However, in control heifers, the total local trichomonal antibody response increased three- to fivefold after infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785822 TI - Efficacy of injectable doramectin against natural Boophilus microplus infestations in cattle. AB - Three experiments were conducted in Latin America--1 in Brazil, 1 in Venezuela, and 1 in Argentina--using a common protocol to investigate the efficacy of a single SC injection of doramectin (200 micrograms/kg of body weight) for treatment and control of Boophilus microplus infestations in grazing cattle. In each experiment, 2 groups of 20 to 27 cattle were allocated on the basis of tick burdens present 24 hours before treatment to a treated or control group, which received saline solution (1 ml/50 kg). All cattle were injected in the mid-dorsal cervical region and examined on treatment day and on posttreatment days (PTD) 8, 14, 21, and 28. On each observation day, the number of engorged and semiengorged ticks on half of each animals was counted and recorded. Doramectin was highly efficacious in removing tick burdens and controlling reestablishment of B microplus under field conditions of continuous reinfestation. Compared with tick counts in the control group, doramectin-treated cattle began to eliminate ticks after treatment and efficacy improved on subsequent observation days. In Brazil, efficacy was 91% at PTD 8 and 14, and increased to 99% or higher at PTD 21 and 28. In Venezuela, efficacy was 100% at PTD 8, 14, and 21 and 92% at PTD 28. In Argentina, efficacy progressed from 94.5% at PTD 8 to 99 and 98.5% at PTD 21 and 28, respectively. The reduction of the number of ticks in the doramectin-treated cattle was significant (P < 0.05) at each observation day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785823 TI - Efficacy of lufenuron against developmental stages of fleas (Ctenocephalides felis felis) in dogs housed in simulated home environments. AB - Twenty-four, adult, female Beagles were arranged by body weight from greatest to least and allocated to 2 groups of 12 dogs, using random numbers. Dogs were housed collectively in 2 adjacent metal buildings, each divided into 4 rooms measuring 2.1 x 3.7 m. Each room was paneled and carpeted and had an access door to the outside with a connecting run that measured 2.1 x 9.1 m. Each run had a surface consisting of 5 cm of pea gravel overlaying 5 cm of sand, and was partially covered by an awning that provided shade at its proximal end. For placement in room/run units, dogs in each of the treated and control groups were alloted to 4 subgroups of 3 dogs each. Each subgroup of dogs was placed in a separate room/run unit. Units containing treatment or control subgroups were alternated to avoid placing identically treated subgroups adjacent to each other. Dogs of subgroups A, C, E, and G were treated with lufenuron monthly at a minimal target dosage of 10 mg/kg of body weight; those of subgroups B, D, F, and H were treated with excipient tablets. Dogs were treated on study days 7, 37, 68, and 98. Each dog was infested with 100 newly emerged, unfed, insectary-reared, adult Ctenocephalides felis on each of study days 0 and 2. Thereafter, infestations on all dogs were dependent on continued development of fleas either in the indoor or outdoor environment. Numbers of fleas on each of the treated and control dogs were determined, using a nondestructive counting technique on days 6, 14, 21, 28, 35, 56, 70, 84, 98, 112, and 119.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785824 TI - Comparative treatment of mares susceptible to chronic uterine infection. AB - Four intrauterine treatment strategies were evaluated for effectiveness in mares that were confirmed to be susceptible to chronic uterine infection. Pretreatment samples were obtained at detection of estrus, and a genital strain of Streptococcus zooepidemicus was infused into the uterus when a preovulatory (> 35 mm) follicle was detected. At 12 hours after inoculation, mares were assigned to 1 of 4 selected treatment groups: autologous plasma, 100 ml (n = 5); potassium penicillin, 5 million U in 100 ml of phosphate-buffered saline solution (PBSS; n = 5); 10 mg of prostaglandin F2 alpha in 100 ml of PBSS (n = 5)' and large-volume lavage with normal saline solution (1,000 ml increments). A fifth group, treated with vehicle alone (100 ml of PBSS), served as a negative control (n = 7). All treatments were administered into the uterus. To assess the effectiveness of the treatment, samples for culture and cytologic examination were collected at 96 hours after bacterial inoculation. An effect of treatment was observed on the number of uterine neutrophils (P = 0.02) and growth of S zooepidemicus (P < 0.01). Intrauterine treatment with potassium penicillin, prostaglandin F2 alpha, and large-volume uterine lavage significantly reduced the growth of S zooepidemicus (P < 0.01) as well as the number of neutrophils (P < 0.02). Autologous plasma reduced the number of neutrophils (P < 0.05), but not growth of S zooepidemicus. There was significant correlation between the number of uterine neutrophils and growth of S zooepidemicus for each treatment group (r = 0.57; P < 0.05). PMID- 7785825 TI - Articular chondrocalcinosis of the humeral head in greyhounds. AB - Of 143 Greyhounds necropsied consecutively, 6 (4%) had chondrocalcinosis of the scapulohumeral joint; lesions were identified in 6 additional dogs. Lesions were seen exclusively in the humeral head, mainly in the plateau region. The lesions in the dogs of the initial group were unilateral, but 2 of the 6 additional dogs had bilateral lesions. Focal mineralization of articular cartilage appeared as a white raised nidus, sometimes surrounded by a translucent halo in the opaque cartilage. Circular, small translucent cartilage foci, with or without beginning mineralization, were adjacent to definitive chondrocalcinosis lesions. Chondrocyte necrosis and matrix degradation were considered to antedate appearance of matrical mineral granules; mineralization of the cartilage was considered a secondary process, but not necessarily an epiphenomenon. Scanning electron microscopy indicated that the chondrocalcinosis lesion was composed of deposits of irregularly fused stone material that, in scanning and transmission electron micrographs, was composed of irregular spheroids, 0.05 to 0.5 micron in diameter. The spheroids contained poorly formed needle-like crystals of apatite. Sparse transformation of the mineral phase into hydroxyapatite was considered to be attributable to a biological mechanism that inhibited phase transition. Cartilage degeneration and chondrocalcinosis of the plateau region of the humeral head appear to be unique lesions that develop in young Greyhounds. It is possible that these lesions are the result of the biomechanical stress of training and racing. PMID- 7785826 TI - Ceftiofur distribution in serum and milk from clinically normal cows and cows with experimental Escherichia coli-induced mastitis. AB - Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/- SEM peak log10 bacterial concentration in milk of 5.03 +/ 0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 microgram/ml, and was 0.20 microgram/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 microgram/ml and 0.7 +/- 0.1 microgram/ml for infected and noninfected cows, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785827 TI - Effect of methacholine on mucociliary transport in bovine trachea in vitro. AB - A method is described to evaluate pharmacologic influence on bovine tracheal mucus transport in vitro. In this model, cholinergic agonist methacholine stimulated transport velocity. Methacholine at concentration of 10(-6)M increased velocity by 13.6%, whereas 10(-5)M increased velocity by 26%. Stimulation was inhibited by atropine. PMID- 7785828 TI - High-performance liquid chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug. AB - A high-performance liquid chromatography method was developed for determination of flunixin in bovine plasma. The extraction procedure was easily performed and made it possible to detect low concentrations of flunixin with high accuracy. The limit of quantitation was 7 ng/ml (relative standard deviation = 18% n = 10). The analytic method permits processing of 60 samples/d. Flunixin, as well as the internal standard (diclofenac sodium), belong to the group of nonsteroidal anti inflammatory drugs, which are known to have a high degree of binding to plasma proteins. Therefore, an evaluation of several buffer systems was undertaken to optimize analytic conditions. Cattle were given 2.2 mg of flunixin melgumine/kg of body weight. In experiment 1, single injections were administered IV to 1 cow and IV and IM to 1 heifer (7 days apart), and pharmacokinetic variables were calculated. The IV data were best described by a two-compartment model. The half life after single IV or IM administration was around 4.0 hours. In experiment 2, the decreasing flunixin concentration was determined after the last of either 4 IM injections daily (n = 3 cows) or 2 IM injections daily (n = 3 cows) administered during a 14-day postpartum period. The half-life, determined between 48 and 96 hours after the last dose, was approximately 26 hours in both groups, and flunixin could be detected in plasma up to 8 days, on average. The protein binding of flunixin was studied, using the method of equilibrium dialysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785829 TI - Cardiovascular effects of epidurally administered morphine and a xylazine morphine combination in isoflurane-anesthetized dogs. AB - Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ECG, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3- concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.02 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included ANOVA for repeated measures. Significance was set at P < 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane maintained anesthesia in dogs. PMID- 7785831 TI - Eicosanoid concentrations in digital venous blood from horses with chronic laminitis. AB - The eicosanoids are a family of lipid-derived autocoids that are released in response to a variety of physical and hormonal stimuli. In this study, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured in the digital veins of clinically normal horses and horses with chronic laminitis to determine whether these arachidonic acid metabolites have a role in mediating signs of hoof pain and lesions associated with chronic laminitis. Horses were evaluated at rest and after a brief exercise period, to determine whether eicosanoids are released into the circulation after mild concussion. Digital vein eicosanoid concentrations in horses with signs of hoof pain attributable to chronic laminitis were not different than those in clinically normal horses. There was no difference in resting and postexercise PGE2 or LTB4 concentrations. Mean digital vein PGE2 concentration for the 2 groups was 187.18 pg/ml, whereas mean digital vein LTB4 concentration for the 2 groups was 74.71 pg/ml. These data do not support the hypothesis that PGE2 and LTB4 have a role in mediating the signs of pain and pathologic features of chronic laminitis. PMID- 7785830 TI - Pharmacokinetics and residues of enrofloxacin in chickens. AB - The pharmacokinetic properties of enrofloxacin were determined in broiler chickens after single IV and orally administered doses of 10 mg/kg of body weight. After IV and oral administrations, the plasma concentration-time graph was characteristic of a two-compartment open model. The elimination half-life and the mean +/- SEM residence time of enrofloxacin for plasma were 10.29 +/- 0.45 and 9.65 +/- 0.48 hours, respectively, after IV administration and 14.23 +/- 0.46 and 15.30 +/- 0.53 hours, respectively, after oral administration. After single oral administration, enrofloxacin was absorbed slowly, with time to reach maximal plasma concentration of 1.64 +/- 0.04 hours. Maximal plasma concentration was 2.44 +/- 0.06 micrograms/ml. Oral bioavailability was found to be 64.0 +/- 0.2%. Statistically significant differences between the 2 routes of administration were found for the pharmacokinetic variables--half-lives of the distribution and elimination phase and apparent volume of distribution and volume of distribution at steady state. In chickens, enrofloxacin was extensively metabolized into ciprofloxacin. Residues of enrofloxacin and the major metabolite ciprofloxacin in fat, kidney, liver, lungs, muscles, and skin were measured in chickens that received an orally administered dose of 10 mg/kg once daily for 4 days. The results indicate that enrofloxacin and ciprofloxacin residues were cleared slowly. Mean muscle, liver, and kidney concentrations of the metabolite ciprofloxacin ranging between 0.020 and 0.075 micrograms/g persisted on day 12 in chickens after dosing. However, at the time of slaughter (12 days), enrofloxacin residues were only detected in liver and mean +/- SEM concentration was 0.025 +/- 0.003 micrograms/g. PMID- 7785832 TI - Adrenocortical function in neonatal and weanling beagle pups. AB - Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785833 TI - Laparoscopic anatomy of the equine abdomen. AB - Laparoscopy was performed on 6 horses (2 mares, 2 geldings, 2 stallions) to determine the normal laparoscopic anatomy of the equine abdomen. After withholding feed for 36 hours, horses were examined from the left and right paralumbar fossae, and the visceral anatomic structures were recorded by videotape and photography. One mare developed emphysema located subcutaneously at the primary laparoscopic portal; otherwise, there were no complications. The anatomic structures of diagnostic importance that were observed in the left half of the abdomen were the hepatic duct; left lateral and quadrate lobes of the liver; stomach; spleen; left kidney with the associated nephrosplenic ligament; segments of jejunum, descending colon, and ascending colon; left side of the male and female reproductive tracts; urinary bladder; vaginal ring; and mesorchium. Important structures observed in the right side of the abdomen were portions of the common hepatic duct; left lateral, quadrate, and right lobes of the liver; caudate process of the liver; stomach; duodenum; right dorsal colon, epiploic foramen; omental bursa; right kidney; base of the cecum; segments of jejunum, descending colon, and ascending colon; urinary bladder; right half of the male and female reproductive tracts; and rectum. PMID- 7785834 TI - Ototoxicity assessment of a gentamicin sulfate otic preparation in dogs. AB - Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment. Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations. PMID- 7785835 TI - Enzyme Engineering XII. Conference proceedings. Deauville, France, September 19 24, 1993. PMID- 7785836 TI - Reaction mechanism for the conversion of 5-monosubstituted hydantoins to enantiomerically pure L-amino acids. AB - The specific conversion of D,L-5-monosubstituted hydantoins to optically pure L amino acids by resting cells of Arthrobacter sp. DSM 7330 has been evaluated. A new nonstereoselective hydantoinase from Arthrobacter sp. DSM 7330 was isolated and characterized. When whole cells were tested, the conversion of D,L-5 methylthioethylhydantoin (D,L-5-MTEH) led to the optically pure intermediate D carbamoylmethionine (D-CM) and to the optically pure amino acid L-methionine. After purification of the hydantoin hydrolyzing enzyme, the probable reaction mechanism of the conversion of 5-monosubstituted hydantoins to enantiomerically pure L-amino acids could be enlightened. PMID- 7785837 TI - Random mutagenesis of the substrate-binding site of a serine protease. A new library of alpha-lytic protease S1 mutants. PMID- 7785838 TI - Micromachining technology and biosensors. PMID- 7785839 TI - A novel electropolymerized sensing layer for biosensors involving entrapped enzyme-phospholipid vesicles. PMID- 7785840 TI - Reconstitution of a functional electron transfer in a biomimetic structure, including an electrode interface, phospholipid and ubiquinone molecules, and a membrane enzyme. PMID- 7785841 TI - In vitro glycosylation of enzymes. Modification of activity and stability. PMID- 7785842 TI - Enzymatic polymerization of p-phenylphenol in aqueous micelles. PMID- 7785843 TI - In vitro protein biosynthesis using ribosome and foreign mRNA. An approach to construct a protein biosynthesizer. PMID- 7785844 TI - Stereoselective microbial reduction of 2-keto-3-(N-benzoylamino)-3-phenyl propionic acid ethyl ester. Synthesis of taxol side-chain synthon. PMID- 7785845 TI - Time course of glutamine in a culture medium during high-density culture of mouse C127 transformants. PMID- 7785846 TI - The design, synthesis, and activity of a ribozyme that specially cleaves rat 28S rRNA. PMID- 7785847 TI - Studies on the engineering of human lysozyme. PMID- 7785848 TI - Relationships between structures and kinetic properties of pancreatic lipases. PMID- 7785849 TI - Structural and functional aspects of an industrial lipase. PMID- 7785850 TI - A new method for estimating the selectivity of lipases for fatty acids and fatty alcohols in organic solvents. PMID- 7785851 TI - DNA-hydrolyzing autoantibodies in autoimmune pathologies. PMID- 7785852 TI - Antiidiotypic antibodies as functional internal images of enzyme-active sites. PMID- 7785853 TI - Study of the abzyme with peroxidase catalytic activity. PMID- 7785854 TI - A new strategy for generating selenium-containing abzyme. Chemical mutation of monoclonal antibodies with substrate-binding sites. PMID- 7785856 TI - Protein disulfide isomerase reaction kinetics in endoplasmic reticulum for monoclonal antibody refolding and assembly. PMID- 7785855 TI - Complementary approach for the determination of histidine in the metal-binding site of an anti-DTPA-indium monoclonal antibody. PMID- 7785857 TI - A multifunctional flow-injection biosensor for the simultaneous determination of ammonia, creatinine, and urea. AB - A strategy for the multifunctionalization of the FIA biosensor was developed. The described multifunctional FIA system offers a fast and simple method for the simultaneous determination of ammonia, creatinine, and urea. The hydrolysis of creatinine by creatinine deiminase (CRDI) or of urea by urease forms ammonia, which is amperometrically detected by an oxygen electrode, based on an enzyme conversion system, glutamate dehydrogenase (GLDH)/glutamate oxidase (GLOD). The split of the stream into three after sample injection and confluence before the GLDH reactor resulted in a three-channel system, into which were set three parallel columns, respectively, filled with immobilized CRDI, urease, and CPG. A triple-peak recording was obtained by putting two delay coils at the channels involving CRDI and urease. Thus the interfering of the endogenous ammonia on the creatinine and urea assay is simultaneously compensated. Furthermore, the problem of great difference in concentration between urea and the other two components is resolved by taking advantage of the differentiated dilution effect for each channel caused from the split-stream, flow-injection system. Linear calibration ranges for ammonia, creatinine, and urea were 0.1-5, 0.2-10, and 2-40 mM, respectively. One run was finished within 5 minutes, and the system was reproducibility good (3 to 5%). The results of the urine assay obtained by the present method will be described in the near future. PMID- 7785859 TI - Enzymatic synthesis of low-calorie sugar substitutes. Cellobiofructose and gentiobiofructose. PMID- 7785858 TI - Enzymatic production of glucooligosaccharides containing alpha-(1-->2) osidic bonds. Potential application in nutrition. PMID- 7785861 TI - Application of sucrose synthase from rice grains for the synthesis of carbohydrates. PMID- 7785860 TI - Transglucosylation of a fungal alpha-glucosidase. The enzyme properties and correlation of isomaltooligosaccharide production. PMID- 7785862 TI - Enzymatic synthesis of partially acylated sucroses. PMID- 7785863 TI - Enzymes from Zymomonas mobilis and their application to glucose determination. PMID- 7785864 TI - Design of novel biocatalysts by "bioimprinting" during unfolding-refolding of fully dispersed covalently immobilized enzymes. PMID- 7785865 TI - New developments in the application of enzymes to synthesis reactions. Peptides and oligosaccharides. PMID- 7785866 TI - Industrial application of immobilized biocatalysts in Japan. PMID- 7785867 TI - 3-Ketoacyl CoA thiolases of a yeast, Candida tropicalis. Properties and functions. PMID- 7785868 TI - Industrial utilization of a hollow-fiber membrane reactor for the controlled lipolysis of butterfat. PMID- 7785869 TI - Production of fibrin polymerization inhibitor from collagen by some proteases. PMID- 7785870 TI - Production of L-amino acids by applying D-amino acid oxidases. PMID- 7785871 TI - Preparation of (R)- and (S)-propylene glycol with baker's yeast. PMID- 7785872 TI - Production of bioactive peptides from corn endosperm proteins by some proteases. PMID- 7785873 TI - Bioremediation using an immobilized cell generator. PMID- 7785874 TI - An integrated bioreactor system for biologically active peptides from isolated soybean protein. PMID- 7785875 TI - Enhanced subtilisin production with spore mutants of Bacillus subtilis and their characterization. PMID- 7785876 TI - Peptic hemoglobin hydrolysis in an ultrafiltration reactor at pilot plant scale generates opioid peptides. AB - Two hemorphins, peptides with opioid activity, have been isolated from a pepsin hydrolysate of bovine hemoglobin, by use of gel permeation (GP) and reverse phase (RP) high-performance liquid chromatography (HPLC). Their primary structure and accurate molecular weights, determined by amino acid analysis and fast atom bombardment (FAB) mass spectrometry, were identical to fragments 31-40 (LVV hemorphin-7) and 32-40 (VV-hemorphin 7) of the beta-chain of bovine hemoglobin. Two other peptides, 34-40 (hemorphin-7) and 34-41 (hemorphin-8) of the beta-chain of bovine hemoglobin, have been synthesized and studied. The opioid potency of these peptides, exhibited by the use of electrically stimulated muscle of isolated guinea pig ileum (GPI), were significant and comparable with some others previously described. Studies of opioid activities and primary structure of hemorphins led us to postulate the important role of arginine and phenylalanine in opioid potency. PMID- 7785877 TI - Photosensitizing activity of porphyrinic peptide hydrolysates derived from bovine hemoglobin. PMID- 7785878 TI - Purification and properties of uricase from Candida sp. and its application in uric acid analysis in serum. PMID- 7785879 TI - Experimentally targeted thrombolytic therapy. Application of modified thrombin conjugated with urokinase. PMID- 7785880 TI - Aspergillus ficuum phytase active site: involvement of Arg and Trp residues. PMID- 7785881 TI - Determination of the intrinsic Michaelis constant of immobilized heparinase. PMID- 7785882 TI - Controlling susceptibility against protease digestion. PMID- 7785883 TI - Micellar enzymology for enzyme engineering. Ideas and realization. PMID- 7785884 TI - Structural effect of reversed micelles of AOT over a recombinant cutinase from Fusarium solani pisi. A steady state fluorescence study. PMID- 7785885 TI - Permanent enzyme microencapsulation in reverse micellar media. PMID- 7785886 TI - Baroenzymology in reversed micelles. PMID- 7785887 TI - Stability and activity of acid phosphatase in reverse micelles. PMID- 7785888 TI - Osteopontin: Role in Cell Signalling and Adhesion. Proceedings of a conference. New Brunswick, New Jersey, October 21-23, 1994. PMID- 7785889 TI - Regulation and function of osteopontin in ras-transformed cells. AB - Transformation of nontumorigenic NIH 3T3 fibroblasts with an activated ras oncogene produces malignant cells that can metastasize. This induction of malignant behavior is due to changes in gene expression induced by Ras-mediated signal transduction. Osteopontin expression is induced in response to Ras, due to increased osteopontin transcription mediated by Ras-responsive regions in the osteopontin gene promoter. The increased expression of osteopontin contributes functionally to the malignant ability of the cells. Ras-transformed cells that express antisense osteopontin RNA show markedly reduced ability to form tumors and to metastasize in experimental animals. Increased osteopontin expression in human tumors thus may also contribute to increased malignancy. Site-directed mutagenesis of recombinant osteopontin protein indicates that an intact RGD sequence is required for cell adhesion and induction of chemotaxis, consistent with the idea that integrin-mediated signal transduction is a consequence of osteopontin binding to cells. Osteopontin may contribute to malignancy by inducing responses in host and/or tumor cells. PMID- 7785891 TI - Conformational analyses on soluble and surface bound osteopontin. AB - Immunohistology of calvarial sections revealed that staining with monoclonal anti osteopontin antibodies (clone MPIIIB10) is minimal unless sections are first treated with EDTA. In contrast, following treatment of sections with EDTA, strong staining of mineralizing osteoid areas and osteoblast-like cells was noted (Fig. 1B). Immunostaining for osteopontin appeared to be specific in that controls which substituted rabbit IgG or normal mouse ascites fluid for monoclonal antibody, or which omitted monoclonal antibody uniformly gave background results (Fig. 1C). In an effort to circumvent problems of antibody accessibility we examined the immunoreactivity of OP when adsorbed to plastic and hydroxyapatite surfaces. Although OP bound to plastic surfaces is reactive with MPIIIB10 antibodies, OP adsorbed to hydroxyapatite crystal surfaces is not recognized by these antibodies as assessed by two detection methods. These results demonstrate that most or all of OP bound to hydroxyapatite exhibits a different conformation than when bound to plastic surfaces. On the basis of immunohistologic results with calvarial sections, we suggest that the conformation of native OP in bone and of isolated OP adsorbed to hydroxyapatite may be similar. Finally, solution circular dichroism and Fourier-transformed infrared spectroscopic studies indicate that the conformation of bone OP is dependent upon its concentration, and, secondarily to the presence or absence of calcium ion. With both spectroscopic methods, addition of calcium appeared to increase the extent of disordered structure. We suggest that these findings support our hypothesis that bone matrix proteins exhibit a different conformation when adsorbed on hydroxyapatite crystal surfaces. Assumption of a more organized secondary structure in concentrated OP solutions (i.e., 15 mg/ml) is consistent with these results in that local concentrations of OP within a semisolid matrix may approach or exceed levels used here. PMID- 7785890 TI - Osteopontin expression in cardiovascular diseases. AB - Adhesive interactions are recognized requirements for cellular proliferation, migration and differentiation during normal morphogenesis as well as disease. By differential cloning, osteopontin was identified as an adhesive protein upregulated during vascular remodeling and neointima formation in both rat models and human vascular diseases including atherosclerosis and restenosis. In functional studies, purified osteopontin promoted adhesion, focal contact formation, and migration of vascular smooth muscle and endothelial cells. Utilizing neutralizing antibodies, three integrin-type receptors, alpha v beta 3, alpha v beta 1, and alpha v beta 5 were found to support cellular adhesion to osteopontin. In contrast, only cells containing the alpha v beta 3 integrin could migrate towards an osteopontin gradient, demonstrating for the first time that different functions of osteopontin are mediated via distinct receptors. These results suggest a model whereby osteopontin, via its integrin-type receptors, contributes to vascular remodeling during development and disease by facilitating smooth muscle migration and simultaneously promoting endothelial coverage of the affected area. PMID- 7785892 TI - The role of Eta-1/osteopontin in the pathogenesis of immunological disorders. PMID- 7785894 TI - Osteopontin and the bone remodeling sequence. Colloidal-gold immunocytochemistry of an interfacial extracellular matrix protein. AB - Relative to other noncollagenous, extracellular matrix proteins in mineralized tissues, colloidal-gold immunocytochemistry has demonstrated that the ultrastructural distribution of osteopontin (OPN) is unique in that this protein preferentially accumulates at mineralized tissue interfaces. In bone, this protein is present as a major component of cell-matrix and matrix-matrix interfacial structures called cement lines and laminae limitantes. In the present article, the implications of this distinct tissue distribution are discussed in terms of the bone remodeling sequence, and a detailed account of the secretion, accumulation and potential role of OPN is presented and related to current theory on the cellular and extracellular matrix events associated with basic multicellular unit (BMU)-based bone remodeling. In this context, a proposal is made describing the production of this protein as one of the earliest, and latest, secretory activities of the osteoblastic lineage, and that this activity manifests itself morphologically as a cement line ('plane') and a lamina limitans, respectively, at bone matrix interfaces. When integrated with other, known functional characteristics of this protein, the present morphological and compositional data indicate that OPN in cement lines and laminae limitantes may participate in initial and late extracellular matrix organization and mineralization, matrix-matrix/mineral adhesion and/or cell adhesion at bone interfaces. PMID- 7785895 TI - Interaction of osteopontin with fibronectin and other extracellular matrix molecules. PMID- 7785893 TI - Localization and expression of osteopontin in mineralized and nonmineralized tissues of the periodontium. AB - To summarize results from various studies focusing on determining the expression/localization of BSP and OPN during tooth root development, there is general agreement that OPN is expressed/localized to the root surface during cementogenesis and is also seen throughout the PDL region. The expression/localization of OPN to odontoblasts and its role in dentinogenesis is less apparent. Recent studies directed at establishing odontoblast cell lines should help to resolve this conflict. Studies on BSP expression during tooth root formation indicate a very precise expression and localization of this molecule during cementogenesis indicating that this molecule may play an important role in the formation of this mineralized tissue. However, as with OPN, the expression of BSP and its role in dentin formation is not clearly defined. PMID- 7785896 TI - Regulation of osteopontin expression in osteoblasts. AB - Osteopontin (OPN) is a prominent bone matrix protein that is synthesized by osteoblastic cells. To elucidate the function of OPN in bone we studied the regulated expression of the rat OPN protein during bone formation in vivo and in vitro. OPN mRNA is expressed by preosteoblastic cells early in bone formation, but the highest expression is observed in mature osteoblasts at sites of bone remodelling. A low-phosphorylated, 55-kDa form of OPN is produced by the preosteoblastic cells, whereas osteoblasts produce a highly phosphorylated, 44 kDa protein; the two forms of OPN corresponding to pp69 and pp62 in transformed rat cells. The synthesis of the 55-kDa OPN correlates with the formation of a 'cement' matrix that is synthesized prior to bone deposition, whereas the 44-kDa OPN synthesized by osteoblasts associates rapidly with hydroxyapatite, possibly regulating crystal growth, and may also provide a substratum for osteoclast attachment. Expression of OPN mRNA is upregulated by growth and differentiation factors (PDGF, EGF, TGF-beta and BMP-7/OP-1) and by mechanical stress, which promote bone formation, as well as by osteotropic hormones (retinoic acid and vitamin D3), which can promote bone resorption and remodelling. However, OPN mRNA is down-regulated by bisphosphonates, which abrogate bone resorption. Regulation of OPN expression is, therefore, consistent with a multiplicity of functions for OPN that involve specific structural motifs in both the synthesis and resorption of bone. PMID- 7785897 TI - Effects of okadaic acid on calcitriol- and phorbol ester-induced expression and phosphorylation of osteopontin in mouse JB6 epidermal cells. PMID- 7785898 TI - Regulation of osteopontin gene expression in osteoblasts. PMID- 7785899 TI - Osteopontin and related phosphorylated sialoproteins: effects on mineralization. AB - Osteopontin is one of a family of phosphorylated sialoproteins found in the extracellular matrices of mineralized connective tissues. Solution studies from a variety of laboratories have shown that while some of these proteins (e.g., osteopontin, dentin sialoprotein) inhibit calcium phosphate production, others, such as bone sialoprotein, can act as a nucleator of calcium phosphate formation. The differences in the behaviors of these proteins can be related to their interactions with mineral crystal nuclei and crystal growth sites. The specificity of these interactions, in turn, can be related to differences in the primary structures of the sialoproteins and to the extent to which they are phosphorylated. In vitro systems for the study of osteopontins and osteopontin related protein effects on mineral deposition are described, along with mechanisms explaining the contrasting abilities of the polyglutamate-containing bone sialoprotein to act as a nucleator, while the polyaspartate-containing osteopontin and dentin sialoproteins inhibit calcium phosphate formation and growth. PMID- 7785900 TI - Osteopontin in urinary stone formation. PMID- 7785901 TI - Osteopontin production by cultured kidney cells. PMID- 7785902 TI - Expression of osteopontin in the inner ear. PMID- 7785903 TI - Phosphorylation of osteopontin by Golgi kinases. PMID- 7785904 TI - Expression of antisense osteopontin RNA in metastatic mouse fibroblasts is associated with reduced malignancy. PMID- 7785905 TI - HL-60 cell differentiation and osteopontin expression. PMID- 7785906 TI - The inhibitory activity of osteopontin on hydroxyapatite formation in vitro. PMID- 7785907 TI - A monoclonal antibody against osteopontin inhibits RGD-mediated cell adhesion to osteopontin. PMID- 7785908 TI - The Puerap motif in the promoter of the mouse osteopontin gene. PMID- 7785909 TI - Upregulation of osteopontin expression by ischemia in rat kidney. PMID- 7785910 TI - The mutagenesis of the RGD sequence of recombinant osteopontin causes it to lose its cell adhesion ability. PMID- 7785911 TI - Expression of osteopontin in a macrophage cell line and in transgenic mice with pulmonary fibrosis resulting from the lung expression of a tumor necrosis factor alpha transgene. AB - The expression level of osteopontin (OPN) mRNA was found to be increased in a macrophage cell line in the presence of recombinant tumor necrosis factor-alpha (TNF-alpha). OPN mRNA level was also explored in the lungs of transgenic mice which were expressing TNF-alpha in type II pneumocytes, a condition leading to pulmonary alveolitis and progressive fibrosis. OPN mRNA was significantly increased in the lungs of these transgenic mice. In situ hybridization showed that it was localized mostly in alveolar macrophages. Since OPN can be induced in macrophages by TNF-alpha stimulation and since on the other hand osteopontin appears to decrease the level of nitric oxide synthase, and thus the production of nitric oxide, osteopontin might also indirectly have an antifibrotic effect. The role played by osteopontin in fibrotic lesions resulting from the release of TNF-alpha deserves further study, since it may be involved in the balance of opposite effects eventually leading to local tissue damage ending in fibrosis. PMID- 7785912 TI - Osteopontin expression in clonal dental pulp cells. PMID- 7785913 TI - Regulated expression of osteopontin in human trophoblasts. PMID- 7785914 TI - Osteopontin gene expression in avian tibial dyschondroplasia. PMID- 7785915 TI - Osteopontin mRNA expression in a chemically-induced model of atherogenesis. PMID- 7785916 TI - Identification of the in vivo phosphorylated sites of secreted osteopontin from cultured chicken osteoblasts. PMID- 7785917 TI - Identification of osteopontin mRNA and protein in rat epididymis and of protein on epididymal sperm. PMID- 7785918 TI - Phosphorylation, glycosylation, and transglutaminase sites in bovine osteopontin. PMID- 7785919 TI - Localization of osteopontin during mouse development. PMID- 7785920 TI - Functional analysis of the osteopontin molecule. PMID- 7785921 TI - Osteopontin inhibits nucleation of calcium oxalate crystals. PMID- 7785922 TI - Effect of recombinant osteopontin on adhesion and migration of P388D1 cells. PMID- 7785923 TI - High expression of osteopontin mRNA in human macrophages but not human vascular smooth muscle cells in culture. PMID- 7785924 TI - Structure of the osteopontin gene and its promoter. AB - We cloned the hOPN gene and its 5' upstream region, and analyzed its exon-intron structure and potential regulatory sequences of the promoter region in comparison with those of mouse and porcine homologues. The hOPN gene consists of 7 exons that are similar to those of the mouse gene, although the hOPN gene is longer than the mouse homologue. This difference is attributable to an insertion of about 1750 bp immediately before exon 4 in the hOPN gene. A region of approximately 285 bp immediately upstream of the hOPN transcription initiation site was highly conserved and contained a number of potential cis regulatory consensus sequences. CAT analysis using SCC-3 cells demonstrated that nucleotides at positions -439 to -270, -124 to -80, and -55 to -39 contained cis-acting enhancing elements, in which the -124 to -80 element was much more active than the others. Deletion of the sequences between -474 and -270 localized the cis elements to the sequence at position -439 to -410, whereas the deletion between 124 to -80 localized it to -124 to -115, and -94 to -80 (data not shown). Gel shift analysis using synthesized double-stranded oligonucleotides corresponding to the 30 bp at position -439 to -410 (data not shown), and 10 and 15 bp regions at positions -124 to -115 and -94 to -80, respectively, as probes revealed that each probe formed one or two bands complexed with a nuclear protein prepared from SCC-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7785925 TI - Characterization of the rat osteopontin gene. Evidence for two vitamin D response elements. PMID- 7785926 TI - Structural and functional domains of osteopontin. PMID- 7785928 TI - [Benign paroxysmal positional vertigo. Apropos of 51 cases]. AB - 51 cases of benign paroxysmal vertigo have been investigated in 3 years. The findings put in evidence: the particular frequency of this pathology (18% of BPPV in a vestibulometry consultation), its opportunist character and the possible association with other more severe pathologies (meningiomas, multiple sclerosis, cerebellar venous angioma, vascular cerebral infarction) or more benign pathologies (labyrinth malformation, middle fossa atrophia). Semont liberatory maneuver revealed to be much efficient (50% of patients free of disease after a single repositioning manoeuvre). Only 3 cases remaining unchanged after 2 years and intractable were proposed for surgery. We mention 7% of bilateral forms and 5% of alternating recurrent forms (sometimes on the right and sometimes on the left side). The recurrence is noted in 50% of BPPV followed at least during one year. We describe a particular topographic form concerning probably a cupulolithiasis of the external canal. 53% of cases beneficiated of CT-scan or of magnetic resonance imaging. The frequency and the possibility of pathological associations with BPPV bring to a particular vigilance for the diagnosis and to a particular care in the affirmation of the benignity in the case of long lasting vertigo (superior to 6 months), or when the nystagmus duration in Hallpike position is superior to 60 seconds. PMID- 7785927 TI - Regulation of avian osteopontin pre- and posttranscriptional expression in skeletal tissues. PMID- 7785929 TI - [Implantation on the cochlear nucleus. Apropos of a patient with bilateral neuroma]. AB - A new auditory brainstem implant (ABI), manufactured by Cochlear, was implanted in a young patient suffering from a large bilateral acoustic neuroma, associated with multiple other tumors due to a tuberor sclerosis of Bourneville. The operating procedure and the first results are described. A short historical summary, the anatomical basis and the difficulties due to side effects of stimulation are exposed. PMID- 7785930 TI - [Clinical development of acute noise-induced acoustic trauma. An evaluation of a study of 250 cases]. AB - Traumatic damage on Cochlea (250 cases) induced by assault gun (F.A.M.A.S.) consists in tinitus and hearing impairement on 6000 Hz. Noise's effects are specific to one Cochlea. Dissociated developments of both tinitus and hearing loss show that their anatomical sites are different. Acoustic injury entails definitive haire cells lesions, cellular biochemical and vascular changes. The treatment that reestablishes or raises cochlear blood flow entails recovery in 80% of cases provided that it is given within 48 hours after the trauma. PMID- 7785931 TI - [Short-term reproducibility of acoustic oto-emissions induced by clicks in adults]. AB - Otoacoustic emissions (OAE) are sounds emitted by the cochlea and recordable in the external ear canal by a miniature microphone. The OAE reflect the existence of an active mechanism within the cochlea. Development of the OAE has spurred much interest because they may used as a valid test for screening and monitoring cochlear changes. The OAE were recorded in 8 normal hearing subjects (15 ears) during nine test sessions under similar conditions. The aim of this work was to study the short-term variability in the amplitude of the emissions. Results of the study indicate that response levels are stable over time in the same ear therefore changes in the response level can be associated with changes in the cochlea. PMID- 7785932 TI - [Role of modern imaging (tomodensitometry and MRI) in cochlear implantation in children]. AB - Since 1989, 40 patients have received implants in the O.R.L. ward of the Hopital d'Enfants Armand Trousseau (Paris). Over the past 2 years, 17 children have undergone radiological assessment combining M.R.I. anf high resolution C.T scanning. Imagery is not the essential stage, and is only used after assessment by a multidisciplinary team. However, the imagery results influence the choice of implant, and sometimes the side to be implanted. C.T is always the first stage as it detects congenital abnormalities, and, for children with a history of bacterial meningitis, it can detect signs of labyrinthine ossification which contraindicate cochlear implantation. These signs are not always visible using tomodensitometry, especially when fibrosis within the canal has not yet ossified. This examination also provides for post-operative confirmation of implant position in case of failure or complication. Over the past 3 years, Magnetic Resonance Imagery has been combined with tomodensitometry, especially with children having a past medical history of meningitis. This examination provides a basis for evaluating the liquid nature of the labyrinth. A G.E. Sygna 1.5 T was used by the authors, employing sequences of volumetric acquisition (S.S.F.P. with 1.5 mm image slices and an angle of 15 to 35 degrees). Hence, modern imagery plays an important role when the decision to implant has already been taken, particularly in the case of profoundly deaf children. M.R.I. is always used in combination with a scanner in cases involving children with a past medical history of meningitis. PMID- 7785933 TI - [Malignant transformation of inverted papilloma of the nasal sinuses.. Apropos of a series of 7 cases]. AB - Seven cases of malignant inverting papillomas are presented (6 men and 1 woman) with ages ranging from 31 to 72 years (mean age: 58 years); the minimum follow up was 37 months. The diagnosis was based on the histopathologic analysis of biopsy in five patients. In two patients the diagnosis was confirmed by the pathological analysis of the specimen. Treatment was always surgical: lateral rhinotomy and total ethmoidectomy. Neoadjuvant chemotherapy was given to four patients. Post operative radiation therapy was delivered in five patients. Five patients on seven died: local recurrence and systemic metastases: 3; systemic metastases: 1; second primary: 1. Reports from the literature are discussed. The authors emphasize the treatment modalities based on complete tumor removal through lateral rhinotomy. PMID- 7785934 TI - [Dysphonia in adults caused by unilateral pseudohypertrophy of the ventricular band with deformation of the thyroid cartilage. Apropos of three cases]. AB - The association of dysphonia appearing in adulthood with unilateral bulging of the false cord associated with a convex deformation of the overlying thyroid cartilage is to be remarked in three cases. The origin, which was presumably acquired by gradual deformation of the thyroid cartilage with age, is discussed in the light of the literature and the clinical history. A past traumatic cause can also be implicated (1 case). CT-Scan is essential for the diagnostic of the cartilage deformation and eliminates laryngeal tumors. In one of the cases reported, we were able to demonstrate the possibility of treatment by CO2 laser resection of the false cord hypertrophy. PMID- 7785935 TI - [Contribution of L lactate and amino-acid enzymatic biosensors for the analysis of Frey syndrome]. AB - Twelve patients with Frey's syndrome after total parotidectomy for plemorphic adenoma were analysed using simultaneously 2 biosensors. Biosensors allowed for detection of L lactate and amino acid level on intact skin. The assay procedure and the results achieved with the simultaneous use of these 2 biosensors are presented. The L lactate biosensor appears to be an interesting tool for Frey's syndrome analysis. The sensibility of the amino acid biosensor is not sufficient enough to allow its use at time of Frey's syndrome analysis. PMID- 7785937 TI - [How to compose an expert report]. PMID- 7785936 TI - [Scopulariopsis brevicaulis otomycosis after tympanoplasty]. AB - We report a case of otomycosis due to Scopulariopsis brevicaulis in a patient who has undergone tympanoplasty 3 months before. Mycological finding led us to consider this fungus as the causative agent. Whereas in vitro studies show a better efficiency of azole derivatives, cure was obtained with nystatine after two treatment failures in our patient. PMID- 7785938 TI - [How to diagnose deafness in a child less than 2 years old]. PMID- 7785939 TI - Stone analysis is not useful in the routine investigation of renal stone disease. PMID- 7785940 TI - Biochemical investigations in renal stone formers. PMID- 7785941 TI - Screening for drugs of abuse. I: Opiates, amphetamines and cocaine. AB - (1) In order to provide an efficient and reliable service for drugs of abuse screening in urine, the laboratory should analyse 20-30 samples per week, and the staff should include a scientist with special expertise in the subject. (2) Turnaround times should be between 2-3 days of sample collection. To achieve this aim it may be necessary to make special arrangements for the delivery of samples to the laboratory. Results should preferably be transmitted by electronic mail or facsimile with the necessary precautions for security and confidentiality: hardcopy reports may also be required. (3) Good communications between the requesting clinician and the laboratory are essential. An advisory service should be provided by the laboratory and clinicians should be encouraged to discuss requests and results with laboratory staff. It is important that the laboratory inform doctors of the range of substances detected and the sensitivity and specificity of laboratory assays. (4) Assays should be performed according to the manufacturer's protocols, or by modified methods that have been rigorously validated. Quality control samples should be included in each analytical run and participation in an external quality assessment scheme, e.g. UKNEQAS, is essential to provide independent confirmation and confidence that results compare with those from other laboratories. Other requirements include adequate training and supervision of staff, and careful recording of samples and results. (5) Drugs to be tested will depend on the drug 'scene' in the area but should include those drugs regularly prescribed for maintenance therapy (e.g. methadone, dihydrocodeine, benzodiazepines), and drugs frequently misused (e.g. heroin, buprenorphine, amphetamines, cocaine). (6) Positive results obtained by preliminary screening methods e.g. EMIT, should be confirmed by another analytical technique, e.g. TLC, GC or GC-MS. If there are potentially serious or legal implications, and in employment and preemployment testing, confirmation of positive results is mandatory. In some cases, e.g. checking for methadone or benzodiazepine compliance, it may be considered unnecessary to confirm positive results although possible spiking of samples cannot be excluded without checking for the presence of metabolites by a chromatographic procedure. PMID- 7785942 TI - Rapid diagnosis of long chain and medium chain fatty acid oxidation disorders using lymphocytes. AB - A method based on the release of tritiated water from [9,10(n)-3H] palmitic and myristic acids previously described for fibroblasts, was adapted for lymphocytes for the rapid diagnosis of fatty acid oxidation disorders. Optimal concentrations for both substrates and linearity of the assay were established. Normal values were established in control subjects of different age groups (58 children and 117 adults) and 16 patients with known fatty acid oxidation disorders were tested. Tritiated water production from patients' lymphocytes was expressed as a ratio between residual oxidations of palmitate and myristate and the results show that this method allows good differentiation between long chain and medium chain fatty acid oxidation defects. PMID- 7785943 TI - Determination of aluminium in serum, dialysate fluid and water by inductively coupled plasma optical emission spectrometry. AB - Methods for the determination of aluminium in serum, dialysate fluid and water by inductively coupled plasma optical emission spectrometry are described and validated. Aluminium was measured at 167 nm using an argon purged monochromator. Matrix effects in serum and dialysate fluid were overcome by using an yttrium internal standard. Serum was found to have a complicated background in the region of 167 nm: careful selection of the wavelength used for background correction is therefore a pre-requisite for accurate analysis. The method for serum was validated by comparison with electrothermal atomization atomic spectrometry and the limit of agreement determined to be +/- 0.3 mumol/L. Routine performance in a quality assessment scheme has been highly satisfactory for a period of 1 year. The method is ideal for fast and accurate monitoring of patients potentially at risk from aluminium toxicity. PMID- 7785944 TI - A rapid method for measurement of the susceptibility to oxidation of low-density lipoprotein. AB - Oxidation of low-density lipoprotein (LDL) may be important in the pathogenesis of atherosclerosis. We describe a method which measures the oxidation resistance of LDL isolated by a rapid procedure without added antioxidants. LDL was isolated from heparinized plasma by density gradient ultracentrifugation and desalted by gel filtration. The protein concentration was standardized to 50 mg/L and oxidation was promoted by copper (2 mumol/L) at 37 degrees C. The total sample preparation time was 2.5 h. Conjugated diene production was monitored at lambda = 234 nm with computation of the lag time. LDL oxidation was inhibited by EDTA but not heparin. Albumin inhibited LDL oxidation but only in concentrations greater than 50 mg/L. LDL was stable in frozen plasma (-70 degrees C) for 10 weeks, but unstable in the isolated and desalted state. The lag time for LDL from patients treated with the antioxidant probucol was markedly prolonged compared to normal subjects. PMID- 7785945 TI - An improved method for the quantitation of apolipoprotein B and apolipoprotein A 1 in dried blood spots. AB - An extraction protocol has been developed to elute apolipoprotein B (apo B) and apolipoprotein A-1 (apo A-1) from dried blood spots with assay of the extracted apolipoproteins by automated immunoturbidimetry. Various extraction media were investigated to assess their elution efficiency and the optimum medium was found to be deionized water. Studies on the rate of elution suggested both apolipoproteins were eluted readily in less than an hour with a recovery of 71% for apo B and 65% for apo A-1. Extracted apo B but not aop A-1 was found to be stable for 24 h when kept at 4 degrees C. The within-batch coefficients of variation (CV) for the combined extraction and assay of apo B were found to be 5.9% and 8.5% at 0.6 g/L and 1.2 g/L respectively. The CVs for apo A-1 were found to be 7.4% at 0.7 g/L and 8.9% at 1.5 g/L. Antiserum from three sources (Immuno, Incstar and Bayer) was investigated for immunoreactivity with apo B and apo A-1 and cross-reactivity with red blood cells was also assessed. Although the antisera from the three companies showed similar immunoreactivity towards apo B and apo A-1, antiserum from Bayer was found to cross-react with red cells. PMID- 7785946 TI - Long-term physical exercise and lipoprotein(a) levels in a previously sedentary male and female population. AB - We investigated the effect of long-term physical exercise on serum lipoprotein(a) levels. 21 sedentary men and 15 sedentary women were trained three to four times a week with increasing intensity during 9 months. After 24 weeks all subjects ran a 15 km race and after 36 weeks a half marathon run (21 km). Blood samples were drawn before the training programme, 5 days before both races and 5 days after the half marathon run. Median (interquartile range) pre-training values in the male group were 32 (11-63) mg/L and in the female group 65 (23-199) mg/L. After 24 weeks of training, serum lipoprotein(a) concentrations had risen significantly in both male and female groups. Moreover, after 36 weeks of training, in preparation for the half marathon competition, median serum lipoprotein(a) rose almost twofold in both groups and was still elevated 5 days later. This study demonstrates that an exercise programme which includes running of increasing distances significantly increases serum lipoprotein(a) concentration. PMID- 7785947 TI - Evaluation of a first-line spectrophotometric screening test for increased urine porphyrin excretion. AB - We compared a spectrophotometric screening test for urine porphyrin concentration with a high performance liquid chromatography (HPLC) method. The screening test gave lower values than those obtained by HPLC, but the overall correlation was good. Occasionally, spectrophotometry failed to detect porphyrins in the urine which were detected by HPLC. The type of porphyria had no influence on the efficacy of the screening method. Receiver operating characteristic plot analysis of the screening test led to a cut-off value of 110 nmol/24 h with a sensitivity of 96% and a specificity of 86%. We conclude that the spectrophotometric screening method is useful for detection of increased total urine porphyrin concentration. PMID- 7785948 TI - The cryopreservation of skin biopsies--a technique for reducing workload in a cell culture laboratory. AB - A method is described for the cryopreservation of skin biopsies at -70 degrees C for subsequent possible reculture. Biopsies stored up to 1 year could be successfully recultured without affecting the time to achieve confluence or the culture failure rate. This technique has been in operation in our department for over 3 years and has resulted in a demonstrable reduction in cell culture costs and a greater flexibility in the acceptance of skin biopsies for culture. PMID- 7785950 TI - Measurement of markers of tobacco smoking in patients with coronary heart disease. AB - 591 patients with a history of coronary heart disease had one or more biochemical markers of tobacco smoking measured. 26% were self reported smokers and a further 4% were apparent 'smoking deceivers'. The urinary nicotine metabolite concentration is an excellent marker for tobacco smoking; breath CO would be a suitable alternative for busy clinics. Half the patients were subjected to regular advice on risk factor management but there was no evidence that this contributed effectively to smoking cessation. Overall smoking cessation rate was poor. PMID- 7785949 TI - D-dimer tests detect both plasmin and neutrophil elastase derived split products. AB - Both plasmin and elastase, a protease released from neutrophil granulocytes, are known to degrade fibrin(ogen). This raises the possibility that elevated plasma levels of split products such as D-dimer may in part result from elastase action. After incubation in vitro of fibrinogen and fibrin clots with elastase, a clearcut increase of D-dimer immunoreactivity was demonstrated by two commercial ELISA kits. In the plasma of 79 patients with inflammatory bowel disease, D-dimer values measured by one of the ELISA kits were correlated significantly not only with markers of thrombin and plasmin activation, but also with elastase-alpha 1 antitrypsin complexes (r = 0.3555; P = 0.014). Thus, the findings of this study suggest that indeed the D-dimer levels in patients with inflammatory disorders are influenced by neutrophil elastase. New tests discriminating effects of activated haemostasis from proteolysis by neutrophil enzymes might be helpful in differential diagnosis and monitoring of therapy. PMID- 7785951 TI - A method of relating whole blood cyclosporin A results by HPLC to Abbott TDx monoclonal and polyclonal immunoassays. PMID- 7785952 TI - Lower values for immunoglobulin M in cerebrospinal fluid when sampled with an atraumatic Sprotte needle compared with conventional lumbar puncture. AB - Immunoglobulin M (IgM) has a very low concentration in cerebrospinal fluid (CSF) compared with serum, and therefore determinations of IgM in CSF are highly sensitive to pre-analytical errors caused by contamination with serum or interstitial fluid. Capillary attraction causes a thin layer of liquid containing serum proteins to be formed inside a conventional (Quincke) needle during penetration of tissue. To investigate this source of pre-analytical error, 35 patients had lumbar punctures using a 22 G atraumatic (Sprotte) or 25 G conventional (Quincke) needle according to a randomized scheme, and the IgM concentrations in CSF and serum were determined. The CSF IgM concentrations for samples taken with a Sprotte needle were significantly lower than those taken with a Quincke needle (P < 0.05), whereas the corresponding serum IgM concentrations and CSF erythrocyte counts did not differ significantly. The difference indicates that CSF IgM concentrations determined after conventional sampling may be falsely increased by contamination. We conclude that IgM concentrations in CSF samples taken with the atraumatic technique are more accurate, and recommend the use of this technique when CSF IgM is to be determined. PMID- 7785953 TI - Effect of short-term corticosteroid administration on the concentration of serum proteins. PMID- 7785954 TI - The stability of parathyroid hormone in blood and serum samples at 4 degrees C and at room temperature. PMID- 7785955 TI - Three different methods for the determination of total homocysteine in plasma. PMID- 7785956 TI - Hypercholesterolaemia presenting in a patient with familial defective apolipoprotein B-100 and hypothyroidism. PMID- 7785957 TI - Hypertriglyceridaemia in a child with hypernatraemia due to a hypothalamic tumour. PMID- 7785958 TI - Fatal isoniazid poisoning. PMID- 7785959 TI - Poor performance of serum separator. PMID- 7785960 TI - Calcium metabolism following renal transplantation. PMID- 7785961 TI - Diseases related to oxygen-derived free radicals. AB - Oxygen-derived free radicals are very important mediators of cell injury and death. Not only are these highly reactive chemical species important in the aging process, but they are either directly or indirectly involved in a wide variety of clinical disorders, such as atherosclerosis, reperfusion injury, pulmonary toxicity, macular degeneration, cataractogenesis, and cancer. In addition, they play an important role in chronic granulomatous disease and act as secondary sources of cellular injury in chronic granulomatous disease and act as secondary sources of cellular injury in chronic inflammatory processes and several disorders of the central nervous system. Furthermore, a wide variety of drugs and xenobiotics are themselves either converted to, or stimulate the formation of, free radicals. Prevention and/or treatment of many of these disorders may be possible by appropriate antioxidant therapy, either currently available or to be discovered through continued research. PMID- 7785962 TI - Renal function in the elderly. AB - Renal size and volume decrease with age, accompanied by intrarenal vascular changes. The number of glomeruli decreases and the mass of the juxtamedullary nephrons falls. The result is a decrease in the filtration area of the glomerular basement membrane and decreased permeability. The glomerular filtration rate (GFR) is reduced with aging. The GFR is approximated by the endogenous creatinine clearance, which falls in parallel with the inulin clearance (the true measure of GFR) and is always greater because of tubular excretion of creatinine. Analytical methods for serum and urine creatinine overestimate its concentration and suffer, to varying degrees, from interferences, making the normal range method dependent. A further uncertainty arises from the use of a correction to standard surface area. Serum creatinine concentration is an insensitive indicator of renal function in the elderly. Deduction of creatinine clearance from serum creatinine concentration, weight and age using one of many formulae gives only approximate values, usually too high, and is unsuitable for debilitated and seriously ill patients. Tubular function, in general, is decreased in the elderly. The ability of the kidney to concentrate urine maximally after water deprivation decreases with age, as does the ability to excrete a water and salt load, particularly during the night. Nocturnal polyuria is common in the elderly. The aged kidney can maintain acid-base balance under normal conditions, but not when subjected to an acid load. PMID- 7785963 TI - The influence of zinc on apoptosis. AB - This review summarizes the evidence that apoptosis is modulated by intracellular excess or deficiency of Zn2+, considers mechanisms whereby Zn2+ may influence apoptosis, and delineates gaps in current knowledge and opportunities for research. The experimental evidence supports four major conclusions: [1] Zinc deficiency, resulting from dietary deprivation of mice, or exposure of cultured cells to membrane-permeable Zn(2+)-chelators, can induce apoptosis; [2] Zinc supplementation, either by pretreating mice with ZnSO4, or adding Zn2+ to the media of cell cultures, can prevent apoptotic death. Zn2+ protects against the apoptosis induced by diverse physical, chemical, or immunologic stimuli in cultured cells of lymphoid, hepatic, or neoplastic origin; [3] Zn2+ does not affect the triggering events or earliest signs of apoptosis, but acts later in the apoptotic pathway, preventing endonucleosomal fragmentation and subsequent cytolysis; and [4] An intracellular pool of chelatable Zn2+ plays a critical role in apoptosis, possibly by modulating the activation or activity of endonuclease(s). These conclusions should alert pharmacologists and physicians to the potential therapeutic applications of zinc compounds and zinc chelators in clinical disorders and diseases that involve apoptosis, and to the relevance of zinc nutrition in such conditions. PMID- 7785965 TI - An enzyme-linked immunosorbent assay for urinary screening of fentanyl citrate abuse. AB - An enzyme-linked immunosorbent assay (ELISA) for quantitation of urinary fentanyl was evaluated as a screening tool for detecting abuse of this potent narcotic. The assay was found to have reproducible calibration curves from 0.5 to 10 ng/mL and a limit of detection of 0.5 ng/mL. Interference by proteins, glucose, or pH was negligible. The assay was specific for fentanyl with little cross-reactivity against despropionyl fentanyl and norfentanyl metabolites, other analgesics and common drugs of abuse. To evaluate its use in humans, urines were collected from 57 normal individuals, 48 patients seen in the Emergency Department, and 18 surgical patients receiving either low (50 micrograms) or moderate fentanyl dosage (200 and 250 micrograms) for routine anesthesia. In patients receiving 50 micrograms (a dose consistent with early abuse), urinary fentanyl was detectable for 3 to 10 h post administration. In patients receiving 200 or 250 micrograms (a dose more consistent with addiction), urinary fentanyl was detectable for longer time periods (> 24 h). These results indicate that the ELISA is sensitive for the detection of recent fentanyl exposure under conditions likely to mimic those in abuse and addiction. The assay is simple to perform, reliable, and can be used to screen urine specimens prior to gas chromatography/mass spectrometry (GC/MS) confirmation. PMID- 7785964 TI - Cell proliferation and apoptosis during development and aging of the rabbit corpus luteum. AB - Corpora lutea (CL) are endocrine ovarian structures that regulate fundamental reproductive events in mammals. The functional lifespan of these structures is finite as CL regress and cease secreting progesterone after species-dependent intervals during nonfertile postovulatory cycles or pregnancy. The signals that regulate CL aging are poorly understood. This study investigates cell growth and programmed cell death or apoptosis in corpora lutea of New Zealand White rabbits. To study cell growth, CL were obtained at various postovulatory days (POD) from animals injected with the deoxyribonucleic acid (DNA) precursor analog bromodeoxyuridine (BUdR). The BUdR-labeled cells were identified by avidin-biotin complex immunocytochemistry, and the mean proliferation index area computed by image analysis. Apoptotic cells were scored and further identified by in situ demonstration of DNA fragmentation. Proliferation in parenchymal, stromal, and endothelial CL cells was significantly elevated at POD 3, 5, 18, and 21 and highest at POD 3 (P < 0.001). The number of apoptotic cells was elevated (P < 0.001) at POD 18 and 21, while 1 percent or less of CL cells were apoptotic at POD 3, 5, and 12. Apoptosis was accompanied by shrinkage or vacuolization of CL cells and increased mean number (P < 0.001) of heterophilic leucocytes at POD 18. These data demonstrate that cell growth is more intense during early luteal development and that cell deletion via apoptosis plays an important role in CL regression. The role of paracrine signals such as microphagic cytokines in CL aging remains to be elucidated. PMID- 7785967 TI - Cytogenetic characterization of three cell lines derived from primary cervical tumors. AB - Braun et al established three cell lines from keratinizing and nonkeratinizing cervical carcinomas. These cell lines were subsequently analyzed for growth properties and physical state of the human papillomavirus type 16 genome. It was found that these cell lines have distinct growth properties in vitro and in vivo. Furthermore, they differ in the physical state of the viral genome. TC-140/7, derived from a keratinizing cervical tumor, contains primarily human papillomavirus type 16 in the episomal state. Both TC-146A and TC-146B, derived from a nonkeratinizing large-cell cervical carcinoma, contain exclusively human papillomavirus type 16 in the integrated state. The chromosomes of these three cell lines were characterized in the present study using GTG-banding analysis. The most striking chromosomal abnormalities noted in the TC-140/7 cell line were the presence of a small metacentric consistent with the morphology of an i(12p) or i(5p), an isochromosome 8q and multiple copies of chromosome 9. For TC-146A, the most notable chromosomal abnormalities were in the presence of a derivative chromosome 7 with additional material present on its long arm, an i(8q) and derivative chromosome 19's. For cell line 146B, the most notable chromosomal abnormalities were found to be a marker resembling a derivative X chromosome, a derivative chromosome 7 with additional material on its long arms, an i(8q), an i(16q) and one or more copies of a marker with morphology resembling i(17q). Fluorescent in situ hybridization experiments using select probes further corroborate the results of the conventional cytogenetic studies. PMID- 7785966 TI - Myoglobin clearance as an early indicator for rhabdomyolysis-induced acute renal failure. AB - Two cases are described to illustrate the use of the myoglobin clearance rate as a predictor of acute renal failure (ARF). Both patients suffered extensive skeletal muscle injury characterized by high total creatinine kinase and urine myoglobin. In the first case, a high myoglobin clearance at admission (27 mL/min) was accompanied by normal serum creatinine and creatinine clearances. This patient recovered without renal complications. The second case also had normal serum creatinine and creatinine clearances at the initial presentation of symptoms, but was accompanied by a very low myoglobin clearance (0.64 mL/min). Within 48 h, this patient developed acute renal failure, with creatinine rising from 1.5 to 5.8 mg/dL, and creatinine clearance dropping from 270 to 2.8 mL/min. Because myoglobin has been recognized as a cause of ARF, these cases help illustrate how the myoglobin clearance rate might be used in evaluating patients with rhabdomyolysis for the development ARF. PMID- 7785968 TI - Poliovirus neutralizing antibody persistence after vaccination with the Sabin vaccine: a follow-up study. AB - In 1976, a cohort survey on the persistence of neutralizing antibodies in children regularly immunized 1 to 4 years earlier with the Sabin attenuated vaccine (OPV) was undertaken in the Venice mainland. Subsequent serological evaluations in the same cohort were carried out in 1983 and 1993. A macroneutralization test using a 1:4 initial serum dilution was utilized in the 1976 and 1983 survey years. In the 1993 survey a microneutralization test using a 1:2 initial dilution was utilized. In this survey, however, sera were tested using both the latter microneutralization test and the former test. Using the former method, the results indicate that the OPV-induced humoral immunity to poliovirus 1 and 2 remain fairly stable after the initial decrease, whereas antibodies to poliovirus 3 are further declining. Using the latter more sensitive method the seropositivity rates were found to be equal or close to 100 percent. The results of our follow-up survey thus indicate that the OPV-induced humoral immunity is long-lasting when tested with a highly sensitive and reproducible method. The clinical protection that ensues after OPV-immunization is probably lifelong similar to that which follows the natural infection. PMID- 7785969 TI - Pharmacokinetics of high-dose intravenous ciprofloxacin in young and elderly and in male and female subjects. AB - The effects of age and gender on the pharmacokinetics of high-dose intravenous ciprofloxacin in a healthy volunteer study were investigated. Plasma ciprofloxacin concentrations were higher in the elderly than in the young, and the pharmacokinetic parameters were not significantly different between the genders. Ciprofloxacin was well tolerated, with the majority of adverse events related to local reactions at the IV site. PMID- 7785970 TI - Ribosylation by mycobacterial strains as a new mechanism of rifampin inactivation. AB - Several fast-growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were determined to be those of 3-formyl-23-[O-(alpha-D-ribofuranosyl)]rifamycin SV and 23-[O-(alpha-D-ribofuranosyl)]rifampin, respectively. To our knowledge, this is the first known example of ribosylation as a mechanism of antibiotic inactivation. PMID- 7785971 TI - Transferable resistance to beta-lactams in a nosocomial strain of Xanthomonas maltophilia. PMID- 7785972 TI - Questionable susceptibility reporting in a multicenter trial. PMID- 7785973 TI - Ginkgo biloba extract EGb 761 is not active against Mycobacterium avium infection in C57BL/6 mice. PMID- 7785974 TI - Insights into erythromycin action from studies of its activity as inducer of resistance. PMID- 7785975 TI - Effect of atovaquone and atovaquone drug combinations on prophylaxis of Pneumocystis carinii pneumonia in SCID mice. AB - The prophylactic efficacies of atovaquone (ATQ) alone and in combination with azithromycin, clarithromycin, rifabutin, proguanil, PS-15, trimethoprim, co trimoxazole, or dapsone were investigated in a SCID mouse model of Pneumocystis carinii pneumonia (PCP). ATQ alone was shown to have a significant dose-related effect, and at 200 mg/kg of body weight per day administered orally, the efficacy of ATQ was comparable to that of Septrin (co-trimoxazole). Of the drugs investigated orally in combination with ATQ, only dapsone (25 mg/kg/day) and to a lesser extent PS-15 (5 mg/kg/day) had any noteworthy antipneumocystis activity (at the doses examined) when administered alone. ATQ drug combinations affected the prophylactic efficacy of a subcurative dosage of ATQ (50 mg/kg/day given orally) in the following ways: dapsone (25 mg/kg/day) or co-trimoxazole (25 mg of sulfamethoxazole plus 5 mg of trimethoprim per kg/day) had no significant effect on ATQ, azithromycin (200 mg/kg/day) or clarithromycin (200 mg/kg/day) had a slight additive effect with ATQ, trimethoprim (100 mg/kg/day) or PS-15 (5 mg/kg/day) had an additive effect with ATQ, and proguanil (25 mg/kg/day) or rifabutin (200 mg/kg/day) had a marked synergistic effect on ATQ. The last result was particularly noteworthy as neither proguanil nor rifabutin was effective against PCP when administered alone. None of the drugs examined antagonized the prophylactic activity of ATQ in experimental PCP in SCID mice. The results suggest that clinical trials of ATQ with synergistic drug combinations may now be justified, particularly if such drug combinations improve ATQ's efficacy and broaden its spectrum of activity. PMID- 7785976 TI - Target for bacteriostatic and bactericidal activities of beta-lactam antibiotics against Escherichia coli resides in different penicillin-binding proteins. AB - The relationship between cell-killing kinetics and penicillin-binding protein (PBP) saturation has been evaluated in the permeability mutant Escherichia coli DC2 in which the antimicrobial activity of beta-lactams has been described as being directly related to the extent of saturation of the PBP target(s). Saturation of a single PBP by cefsulodin (PBP 1s), mecillinam (PBP 2), and aztreonam (PBP 3) resulted in a slow rate of killing (2.5-, 1.5-, and 0.8-log unit decreases in the number of CFU per milliliter, respectively, in 6 h). Saturation of two of the three essential PBPs resulted in a marked increase in the rate of killing, which reached the maximum value when PBPs 1s and 2 were simultaneously saturated by a combination of cefsulodin and mecillinam (4.7-log unit decrease in the number of CFU per milliliter in 6 h). Inactivation of all three essential PBPs by the combination of cefsulodin, mecillinam, and aztreonam further increased the killing kinetics (5.5-log-unit decrease in the number of CFU per milliliter), and this was not significantly changed upon additional saturation of the nonessential PBPs 5 and 6 by cefoxitin. Similar relationships between PBP saturation and killing kinetics were obtained with imipenem and meropenem at concentrations which inhibited only one PBP (PBP 2), only two PBPs (PBP 1s and 2), or all three essential PBPs. Saturation of one or more PBPs also resulted in a different rate of bacteriolysis, the highest rate being obtained by the cefsulodin-mecillinam combination and by 5 micrograms of either imipenem or meropenem per ml. All of these conditions caused saturation of PBP 2 and saturation or extensive binding of PBP 1s. However, none of these conditions caused determined the fastest possible rate of killing, which occurred only when all three essential PBPs were saturated. It was concluded that the actual killing effect of beta-lactams is reflected by killing rates that approach the fastest possible rate for the given microorganism and that the targets for the bactericidal activity are precisely those PBPs whose saturation or binding occurs under conditions. PMID- 7785977 TI - Increasing antimicrobial resistance of Shigella isolates in Israel during the period 1984 to 1992. AB - Recent (1984 to 1992) trends in the antimicrobial resistance of Shigella isolates in Israel were studied by analyzing the results of 106,000 stool cultures, 3,511 of which yielded Shigella spp. Over the study period, resistance to trimethoprim sulfamethoxazole (TMP-SMX) increased from 59 to 92% (P = 0.0038) and that to ampicillin increased from 13 to 86% (P < 0.0001). Resistances to nalidixic acid, chloramphenicol, and broad-spectrum cephalosporins remained low. Shigella sonnei, which currently accounts for 90% of Shigella infections, was more resistant than S. flexneri to TMP-SMX (81 versus 57%, P < 10(-6)), ampicillin (42 versus 32%, P < 10(-5)), and tetracycline (38 versus 28%, P < 10(-5)). S. boydii and S. dysenteriae were relatively rare. Seasonality in antimicrobial resistance was found, with summer isolates being less resistant to TMP-SMX, ampicillin, or both than isolates obtained over the rest of the year (P < 10(-5)). We conclude that the resistance of shigellae, especially S. sonnei, to TMP-SMX and ampicillin is increasing to approximately 90%. Resistance should be recorded locally, and empiric therapy for suspected shigellosis should be changed accordingly. PMID- 7785979 TI - Inducible and constitutive expression of resistance to glycopeptides and vancomycin dependence in glycopeptide-resistant Enterococcus avium. AB - A clinical isolate of Enterococcus avium, Ea1, which exhibited inducible, low level resistance to vancomycin and teicoplanin, and two mutants selected from this strain, Ea3 and Ea31, were studied. Ea3 was vancomycin dependent and derived from Ea1, while Ea31 was not vancomycin dependent, was constitutively resistant, and was derived from Ea3. Hybridization studies revealed that vanA was present in Ea1 and suggested that it was located on a high-molecular-weight plasmid. In the absence of induction, Ea1 synthesized only the natural UDP-MurNAc-pentapeptide precursor, and after induction it synthesized an additional precursor identified as UDP-MurNAc-tetrapeptide-D-lactate. The latter was the only precursor found in Ea3 and Ea31, even after precursor accumulation. From these results, we infer that (i) the low level of resistance to glycopeptides in strain Ea1 may be in part due to the residual synthesis of the normal precursor and (ii) the vancomycin dependence of mutant Ea3 could be due to the fact that this strain does not produce any peptidoglycan precursor in the absence of induction. PMID- 7785978 TI - Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens. AB - The distribution of strains producing metallo-beta-lactamase among 105 strains of Serratia marcescens was investigated. All of these strains were isolated in seven general hospitals located in Aichi Prefecture, Japan, from April to May 1993. Southern hybridization analysis suggested that four S. marcescens strains, AK9373, AK9374, AK9385, and AK9391, had a metallo-beta-lactamase genes similar to the blaIMP gene found by our laboratory (E. Osano, Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato, Antimicrob. Agents Chemother. 38:71-78, 1994), and these four strains showed resistance to carbapenems as well as to the other broad-spectrum beta-lactams. In particular, strains AK9373, AK9374, and AK9391 showed an extraordinarily high level resistance to imipenem (MICs, > or = 64 micrograms/ml), whereas strain AK9385 demonstrated moderate imipenem resistance (MIC, 8 micrograms/ml). The imipenem resistance of AK9373 was transferred to Escherichia coli CSH2 by conjugation with a frequency of 10(-5). The DNA probe of the blaIMP gene hybridized to a large plasmid (approximately 120 kb) transferred into the E. coli transconjugant as well as to the large plasmids harbored by AK9373. On the other hand, although we failed in the conjugational transfer of imipenem resistance from strains AK9374, AK9385, and AK9391 to E. coli CSH2, imipenem resistance was transferred from these strains to E. coli HB101 by transformation. A plasmid (approximately 25 kb) was observed in each transformant which acquired imipenem resistance. The amino acid sequence at the N terminus of the enzyme purified from strain AK9373 was identical to that of the metallo-beta-lactamase IMP-1. In contrast, strains ES9348, AK9386, and AK93101, which were moderately resistant to imipenem (MICs, > or = 4 to < or = 8 micrograms/ml), had no detectable blaIMP gene. As a conclusion, 19% of clinically isolated S. marcescens strains in Aichi Prefecture, Japan, in 1993 were resistant to imipenem (MICs, > or = 2 micrograms/ml), and strains which showed high-level imipenem resistance because of acquisition of a plasmid-mediated blaIMP-like metallo-beta-lactamase gene had already proliferated as nosocomial infections, at least in a general hospital. PMID- 7785980 TI - Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits. AB - Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes. PMID- 7785981 TI - Quantitation of slow drug release from an implantable and degradable gentamicin conjugate by in vivo magnetic resonance imaging. AB - A biodegradable model hydrogel containing a covalently bound aminoglycoside in which drug release can be monitored by magnetic resonance imaging (MRI) in vivo was developed. The hydrogel consists of the bishydroxysuccinimide ester of polyethylene glycol disuccinate cross-linked albumin, to which gentamicin and Gd diethylenetriaminepentaacetic acid are covalently attached in stochiometric quantities. MRI allowed us to depict the three-dimensional structure of implanted gels, to accurately calculate their volumes, and thus to calculate the concentration of hydrogel-bound gentamicin. The correlation coefficient for the concentration of released gentamicin and the hydrogel volume was 0.965. Free and hydrogel-released gentamicin conjugates had similar antibiotic efficacies when tested in microbiological agar diffusion assays. In vivo, hydrogel-released gentamicin had a longer half-life in plasma than unaltered gentamicin (5.6 versus 0.7 h), presumably because of residual bound polyethylene glycol residues. Hydrogel implants into rats resulted in a prolonged (7 to 10 days) release of gentamicin and a decreased 24-h mortality in mice infected with a lethal dose of Pseudomonas aeruginosa. The results indicate the feasibility of imaging and quantitating therapeutic drug concentrations in vivo by MRI. PMID- 7785983 TI - In vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent. AB - This study evaluated the in vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent. The drug inhibited all tested members of the family Enterobacteriaceae at < or = 0.5 microgram/ml and all tested Pseudomonas aeruginosa, Burkholderia (Pseudomonas) cepacia, and Xanthomonas maltophilia strains at < or = 2 micrograms/ml. All but two strains of gram-positive bacteria were inhibited by < or = 1 microgram of the new drug per ml, including isolates highly resistant to ciprofloxacin. PMID- 7785982 TI - Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo. AB - Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1. PMID- 7785984 TI - Evaluation of maduramicin and alborixin in a SCID mouse model of chronic cryptosporidiosis. AB - Two polyether ionophores, maduramicin and alborixin, were evaluated for anticryptosporidial activity in a severe combined immune deficient (SCID) mouse model of cryptosporidiosis. Groups of SCID mice were inoculated with 10(6) oocysts of bovine origin by oral gavage. Maduramicin or alborixin was administered beginning 4 weeks postinfection at 3 mg/kg of body weight per day. Maduramicin treatment resulted in a 96% reduction in fecal parasite load over the 3-week treatment period (P < 0.003). This reduction correlated with decreases in tissue parasite loads observed in histological sections of the small intestine (P < 0.000002) and the colon (P < 0.000006). A significant decrease in oocyst shedding was also observed after a 3-week treatment with alborixin (71% reduction, P < 0.01). Maduramicin was also evaluated in a relapsing model of cryptosporidiosis in which the infection was observed to recur after treatments were discontinued. Some toxicity, as demonstrated by weight loss, was observed with both maduramicin and alborixin. Both drugs exhibited significant anticryptosporidial activities with concomitant moderate toxicity. These polyether ionophores should be valuable as positive controls in compound evaluation studies and as lead compounds for chemical optimization (modification). PMID- 7785985 TI - Alterations in penicillin-binding protein 2B from penicillin-resistant wild-type strains of Streptococcus pneumoniae. AB - The 1.5-kb transpeptidase-encoding region (TER) of penicillin-binding protein (PBP) 2B was amplified and sequenced from 18 penicillin-resistant isolates of Streptococcus pneumoniae, with each isolate representing a different DNA fingerprint profile of the TER. PBP 2B TERs from penicillin-resistant isolates revealed extensive sequence divergence from the penicillin-susceptible R6 strain, differing by up to 170 nucleotide substitutions and resulting in up to 38 alterations in the amino acid sequence of the protein. All penicillin-resistant isolates showed sequence divergence within a +/- 300-bp area at the center of the PBP 2B TER. Although a number of amino acid substitutions were found within this central area of PBP 2B, only two substitutions were common to all resistant isolates, namely, Thr-252 replacement by Ala and Glu-282 replacement by Gly. These two substitutions appear to be essentially associated with a decreased affinity of PBP 2B for penicillin. A second block of divergent nucleotide sequence was prominent amongst isolates with high levels of resistance. This was a +/- 100-bp area of the TER around nucleotide 1300 and included the substitution of Gly for Asp-431, which was the only amino acid substitution within this area that was common to all isolates. These data may assist in the definition of the structural changes in the penicillin-binding site of PBP 2B associated with penicillin resistance in S. pneumoniae. PMID- 7785986 TI - In vitro activity of D0870 compared with those of other azoles against fluconazole-resistant Candida spp. AB - We compared the in vitro activity of a new triazole, D0870, with those of fluconazole, itraconazole, and ketoconazole against 41 clinical isolates of fluconazole-resistant Candida belonging to nine different species. The 50% inhibitory concentrations (IC50s) were determined by a microdilution method with morpholinopropanesulfonic acid (MOPS)-buffered RPMI medium and an inoculum of approximately 10(4) yeasts per ml. After incubation for 48 h at 37 degrees C the optical density at 550 nm was measured. The IC50 was the lowest drug concentration which reduced the optical density at 550 nm by > or = 50% compared with that for a drug-free control. D0870 had significant activity against many of the isolates. Its activity was comparable to that of ketoconazole, slightly superior to that of itraconazole, and markedly superior to that of fluconazole against Candida albicans. Against Candida glabrata, Candida krusei, and Candida inconspicua, it had activity similar to those of itraconazole and ketoconazole but had activity superior to that of fluconazole. D0870 IC50s for some isolates were increased. This may be due to cross-resistance mechanisms because the IC50s of both itraconazole and ketoconazole for these isolates were often high. When IC50s and IC80s were compared there was a marked organism and drug variation. With C. glabrata much higher endpoints for itraconazole were observed when an IC80 endpoint was used. For C. albicans there was also a significant shift upward in endpoints for itraconazole and ketoconazole. Values were changed little when IC50 and IC80 endpoints of D0870 were compared. For 35 of 41 isolates tested the D0870 IC50 was less than the 2.5-mg/liter breakpoint threshold proposed previously. Therefore, D0870 may be a useful agent for the therapy of infections caused by fluconazole-resistant Candida spp. PMID- 7785987 TI - Erythromycin shortens neutrophil survival by accelerating apoptosis. AB - Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To evaluate the anti-inflammatory action of erythromycin, we examined the survival of isolated neutrophils with and without erythromycin. Erythromycin shortened neutrophil survival in a dose-dependent fashion, with a maximum effect at 10 micrograms/ml [corrected] and above. Survival at 24 h was 63.4% in medium with 10 micrograms of erythromycin per ml compared with 82.7% in control medium (P < 0.01). This shortening of survival was brought about by acceleration of apoptosis, as evidenced by transmission electron microscopy. In a manner similar to that of erythromycin, other macrolide antibiotics, i.e., clarithromycin, roxithromycin, and midecamycin, also shortened neutrophil survival, but neither the beta-lactams ampicillin and cefazolin nor the aminoglycoside gentamicin affected their survival. Erythromycin increased intracellular levels of cyclic AMP (cAMP) to 150% of control levels in neutrophils. Forskolin, rolipram, and dibutyryl-cAMP, which are known to increase intracellular cAMP levels, also shortened neutrophil survival. H-89, an inhibitor of cAMP-dependent protein kinase A, partially blocked the survival-shortening effect of erythromycin. Our findings suggest that erythromycin shortens neutrophil survival at least in part through elevation of intracellular cAMP levels. PMID- 7785988 TI - Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice. AB - The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment. Mice were infected with the MO-1 strain. Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection. At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens. Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo. PMID- 7785990 TI - Primary structure of OXA-3 and phylogeny of oxacillin-hydrolyzing class D beta lactamases. AB - We determined the nucleotide sequence of the blaOXA-3(pMG25) gene from Pseudomonas aeruginosa. The bla structural gene encoded a protein of 275 amino acids representing one monomer of 31,879 Da for the OXA-3 enzyme. Comparisons between the OXA-3 nucleotide and amino acid sequences and those of class A, B, C, and D beta-lactamases were performed. An alignment of the eight known class D beta-lactamases including OXA-3 demonstrated the presence of conserved amino acids. In addition, conserved motifs composed of identical amino acids typical of penicillin-recognizing proteins and specific class D motifs were identified. These conserved motifs were considered for possible roles in the structure and function of oxacillinases. On the basis of the alignment and identity scores, a dendrogram was constructed. The phylogenetic data obtained revealed five groups of class D beta-lactamases with large evolutionary distances between each group. PMID- 7785989 TI - Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria. AB - Cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) is a nucleotide analog with activity against human cytomegalovirus (CMV). A phase I/II dose escalation trial was conducted with asymptomatic human immunodeficiency virus (HIV)-infected patients with CMV viruria to determine its pharmacokinetics, maximally tolerated dose, and preliminary antiviral activity against CMV. Qualitative CMV blood and urine cultures were monitored weekly to assess anti-CMV activity. Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per microliters (median, 39) were enrolled in six dose-ranging groups. The first five groups enrolled four patients each to receive cidofovir infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12 weeks. The sixth group enrolled one patient who received infusions of 5 mg/kg of body weight every other week. Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity. Seventeen patients experienced proteinuria on one or more occasions; 6 of them experienced at least 2+ proteinuria. Four patients did not complete the study as planned because of renal toxicity. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated. The dose-limiting toxicity is renal; however, concurrent administration of probenecid may be protective. The maximally tolerated weekly intravenous dose with probenecid is approximately 5 mg/kg. Efficacy trials with CMV disease will define the therapeutic utility and optimal dosing interval for cidofovir. PMID- 7785991 TI - Chlorhexidine susceptibilities of mutans streptococcal serotypes and ribotypes. AB - The susceptibilities of 379 clinical mutans streptococcal isolates to chlorhexidine (CHX) were tested by agar dilution according to the standards of the National Committee for Clinical Laboratory Standards. Isolates were obtained from saliva samples of 34 young mothers who had high or moderate salivary levels of mutans streptococci at baseline. Samples were collected on three occasions, before childbirth, when each child was 6 months old, and 1 year later. Of these isolates, 50% were inhibited at 1 microgram of CHX per ml, 90% were inhibited at 2.0 micrograms/ml, and all were inhibited at 4.0 micrograms/ml. The MICs for Streptococcus mutans isolates (serotypes c, e, and f) were lower than those for Streptococcus sobrinus isolates (serotypes d and g). In some subjects, the MICs for isolates of the same serotype were different. This phenomenon was studied by ribotyping isolates (n = 45) from selected subjects (n = 7). It was found that if there were intraindividual differences in the MICs for isolates of the same serotype, then the ribotypes of these isolates were different. In order to decrease the mutans streptococcal infection risk for children, 24 mothers (test group) brushed their teeth periodically with a gel that contained 0.3% CHX digluconate and 0.2% NaF, pH 5.8, between the second and third sampling occasions. The gel was used twice a day for the first 10 days of each month. Development of resistant strains during CHX-NaF gel use was not detected. The serotype distribution of isolates from the test group after 1 year of periodic CHX-NaF gel use did not differ from that at baseline. Periodic CHX-NaF gel brushing did not lead to lower salivary mutans streptococcal counts. PMID- 7785992 TI - SHV-7, a novel cefotaxime-hydrolyzing beta-lactamase, identified in Escherichia coli isolates from hospitalized nursing home patients. AB - Four ceftazidime-resistant Escherichia coli strains were isolated from elderly nursing home patients in a New York hospital during 1993. Strains MCQ-2, MCQ-3, and MCQ-4 were determined to be identical by pulsed-field gel electrophoresis and plasmid profiles, whereas strain MCQ-1 was unique. Strain MCQ-1 was determined to produce a TEM-10 beta-lactamase. Strains MCQ-2, MCQ-3, and MCQ-4 were also noted to be resistant to cefotaxime. These three strains produced two beta-lactamases with pIs of 5.4 (TEM-1) and 7.6. beta-Lactamase assays revealed that the pI 7.6 enzyme hydrolyzed cefotaxime faster (at a relative hydrolysis rate of 30% compared with that of benzylpenicillin) than either ceftazidime or aztreonam (relative hydrolysis rates of 13 and 3.3%, respectively). Nucleotide sequencing of the gene encoding the pI 7.6 beta-lactamase from strain MCQ-3 revealed a blaSHV-type gene differing from the gene encoding SHV-1 at four nucleotides which resulted in amino acid substitutions: phenylalanine for isoleucine at position 8, serine for arginine at position 43, serine for glycine at position 238, and lysine for glutamate at position 240. This novel SHV-type extended-spectrum beta lactamase is designated SHV-7. PMID- 7785993 TI - Detection of amphotericin B-resistant Candida isolates in a broth-based system. AB - Because of the limited ability of the National Committee for Clinical Laboratory Standards proposed M27P methodology to detect resistance to amphotericin B by Candida isolates, we sought to identify alternative media and pH conditions that could reliably identify resistant isolates. Antibiotic Medium 3 broth (also known as Penassay broth) buffered to pH 5 or pH 7 produced superior results and readily identified a series of resistant isolates. PMID- 7785994 TI - Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus. AB - The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM 17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem. PMID- 7785996 TI - Effect of testing method on apparent activities of antiviral disinfectants and antiseptics. AB - This study was designed to evaluate the independent effects of various test methods on the activities of antiviral chemical germicides. The activities of germicides against MS2 and phi 6 bacteriophages in a new porcine tissue carrier model were compared to those obtained by four other methods (suspension, glass carrier, tile carrier, and fingerpad tissue carrier tests). After a 1-min contact followed by neutralization (and elution off the carriers), the residual virus in the treated samples was quantified and the amount was compared with that in the saline controls. Antiviral activity was highly dependent on the test method for both viruses and was always greatest in suspension tests and lowest in tissue carrier tests. Results obtained for hydrophilic MS2 with the porcine tissue carrier were comparable to those from fingerpads, but lipophilic phi 6 was subject to spontaneous inactivation on human skin and proved unsuitable for fingerpad testing. These data indicate that the activities of germicides in tests with nonbiological substrates may overestimate antiviral antiseptic activity on skin surfaces. Products intended for use as antiviral antiseptics or hand-washing agents should be evaluated in a tissue carrier system. The porcine tissue carrier model provides a safe, inexpensive, accurate, and reproducible method for testing the activities of antiseptics. PMID- 7785995 TI - Trends in susceptibility of Neisseria gonorrhoeae to ceftriaxone from 1985 through 1991. AB - The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline. From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County. MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study. Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991. The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991. The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea. Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community. PMID- 7785997 TI - Fluconazole, D0870, and flucytosine treatment of disseminated Candida tropicalis infections in mice. AB - D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herein we have evaluated the efficacy of D0870, alone and combined with flucytosine, in a murine model of disseminated Candida tropicalis infection. Four isolates of C. tropicalis were evaluated. Two were highly susceptible in vitro to fluconazole, and two were resistant to fluconazole. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropicalis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for > 10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptible C. tropicalis. D0870 was more potent than fluconazole and was effective in fluconazole-resistant isolates. Flucytosine was consistently effective when used alone but did not consistently add to the benefit of D0870 or fluconazole. D0870 has potential in treatment of candidiasis caused by C. tropicalis, including fluconazole-resistant isolates. PMID- 7785998 TI - Comparison of ampicillin-sulbactam regimens simulating 1.5- and 3.0-gram doses to humans in treatment of Escherichia coli bacteremia in mice. AB - A mouse model of bacteremia was used to compare the efficacies of 1.5- and 3.0-g intravenous doses of ampicillin-sulbactam. Seven strains of Escherichia coli producing various levels of TEM-1 beta-lactamase were used as the challenge isolates. These strains included six clinical isolates (MICs from 2/1 micrograms/ml [with 2 and 1 microgram/ml being the respective concentrations of ampicillin and sulbactam] to 32/16 micrograms/ml) with similar degrees of virulence in mice and a laboratory genetic transformant (E. coli AFE) which hyperproduces TEM-1 (MIC = 128/64 micrograms/ml). Human pharmacokinetics were simulated by injecting mice subcutaneously twice (1 h apart) with ampicillin sulbactam at concentrations of 40 mg/kg of body weight (1.5 g) and 80 mg/kg (3.0 g). Against two clinical isolates for which ampicillin-sulbactam MICs were < or = 8/4 micrograms/ml, no difference was observed in either the rate or level of killing between the two doses, and both doses were 100% protective against lethal infection. Against the four clinical isolates for which ampicillin-sulbactam MICs were between 16/8 and 32/16 micrograms/ml, a slight delay in killing was noted with three of the strains. This delay was followed by a rapid 2- to 3-log drop in the level of bacteremia, and both doses of ampicillin-sulbactam were 100% protective against lethal septicemia. With strain AFE, no killing was observed with the 40-mg/kg dose compared with a 2-log killing with the 80-mg/kg dose. This difference in killing correlated with a decreased protective efficacy of the 40 mg/kg dose. These data suggest that the 1.5-g preparation of ampicillin-sulbactam is as effective as the 3.0-g dose in the treatment of experimentally induced E. coli bacteremia, as long as ampicillin-sulbactam MICs are 32/16 micrograms/ml or less. PMID- 7785999 TI - Prospective randomized comparison of cefepime and cefotaxime for treatment of bacterial meningitis in infants and children. AB - Ninety infants and children were prospectively randomized to receive cefepime (n = 43) or cefotaxime (n = 47) for therapy of bacterial meningitis. The two treatment groups were comparable in terms of age, duration of illness before enrollment, history of seizures, clinical status on admission, and etiology. Six (7%) patients died--two treated with cefepime and four treated with cefotaxime. Clinical response, cerebrospinal fluid sterilization, development of complications, antibiotic toxicity, and hospital stay were similar for the two treatment regimens. Concentrations of cefepime in cerebrospinal fluid varied from 55 to 95 times greater than the maximal MIC required by the causative pathogens. Audiologic and/or neurologic sequelae were found in 16% of the cefepime-treated patients and 15% of the cefotaxime-treated patients examined 2 to 6 months after discharge. We conclude that cefepime is safe and therapeutically equivalent to cefotaxime for management of bacterial meningitis in infants and children. PMID- 7786000 TI - Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection? AB - Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used concurrent controls, 14 studies used historic controls. To test this assumption, three observations from the two types of studies were compared. (i) The differences between observed and expected event rates for each study were used to perform a meta-analysis. This revealed that the summary odds ratios for bacteremia and respiratory infection were marked by significant heterogeneity (P > 0.95) and inconsistencies between those derived from studies with concurrent versus studies with historic controls. (ii) Where the data were available, the rates of acquisition of colonization in control groups were higher in studies with concurrent controls than in studies with historic controls. (iii) At least four studies with concurrent controls have shown a pattern of pathogenic isolates consistent with cross-infection between groups. These results are contrary to the initial assumption and suggest the possibility that SDD represents a major cross infection hazard. PMID- 7786001 TI - In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs. AB - The potency of antimalarial dihydrofolate reductase inhibitors, alone and in synergistic combination with dihydropteroate synthetase inhibitors, against the Kenyan K39 strain of Plasmodium falciparum (pyrimethamine resistant) and against normal replicating human bone marrow cells in in vitro culture has been studied. Therapeutic indices and rank order of synergistic potency were derived. Trimethoprim, pyrimethamine, and the quinazolines WR159412 and WR158122 had the smallest therapeutic indices (1.39, 4.38, 2.56, and 90.0, respectively), while the three triazines clociguanil, WR99210, and chlorcycloguanil had the largest (3,562, 3,000, and 2,000, respectively). In rank order of decreasing activity against P. falciparum, the six most potent drug combinations were WR99210 dapsone, chlorcycloguanil-dapsone, WR158122-dapsone, WR159412-dapsone, WR159412 sulfamethoxazole, and chlorcycloguanil-sulfamethoxazole; pyrimethamine sulfadoxine was the least potent combination. These experiments form a basis for the selection of rapidly eliminated antifolate combinations for further clinical testing. PMID- 7786002 TI - Treatment of experimental endocarditis due to methicillin-susceptible or methicillin-resistant Staphylococcus aureus with trimethoprim-sulfamethoxazole and antibiotics that inhibit cell wall synthesis. AB - Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 micrograms/ml and 0.06 and 0.25 microgram/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts. PMID- 7786003 TI - Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole. AB - We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be > 10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a > 90% reduction in fungal load (P < 0.05) and 33% were sterile. After 4 weeks, all had a > 99% reduction in fungal load (P < 0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a > 90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model. PMID- 7786004 TI - In vitro evaluation of ABT-719, a novel DNA gyrase inhibitor. AB - ABT-719 (A-86719.1) is the first compound of a new class of novel DNA gyrase inhibitors, the 2-pyridones, with potent antibacterial activity against gram positive, gram-negative, and anaerobic organisms. ABT-719 was more active than ciprofloxacin, sparfloxacin, and clinafloxacin against gram-positive bacteria. ABT-719 was particularly active against Staphylococcus aureus (MIC at which 90% of the isolates were inhibited [MIC90] = 0.015 micrograms/ml) and Streptococcus pneumoniae (MIC90 = 0.03 micrograms/ml). ABT-719 was also the most active of the compounds tested against ciprofloxacin-resistant S. aureus isolates, with an MIC90 of 0.25 micrograms/ml, compared with 64 micrograms/ml for ciprofloxacin. Against gram-negative organisms, ABT-719 was as active as or slightly more active than ciprofloxacin and was the most active compound against ciprofloxacin resistant Pseudomonas aeruginosa (MIC90 = 2.0 micrograms/ml). ABT-719 was also the most active compound against both gram-positive and gram-negative anaerobes, with MIC90s ranging from 0.12 to 0.25 micrograms/ml. PMID- 7786006 TI - Intracellular activities of roxithromycin used alone and in association with other drugs against Mycobacterium avium complex in human macrophages. AB - Recent reports have shown that roxithromycin possesses significant activity against atypical mycobacteria, including the Mycobacterium avium complex (MAC), and that its extracellular anti-MAC activity is further enhanced in two- or three drug combinations with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine. In accordance with the above data, the anti-MAC potential of roxithromycin used alone and in combination with the above-mentioned antituberculous drugs was screened intracellularly against five clinical MAC isolates (from both human immunodeficiency virus-positive and human immunodeficiency virus-negative patients), phagocytized by human monocyte-derived macrophages. The results showed that roxithromycin used alone and within clinically achievable levels was active against all of the MAC isolates tested. Screening of two-drug combinations showed that both rifampin and clofazimine further increased the intracellular activity of roxithromycin against all five isolates by 35 to 80% (ethambutol, ofloxacin, and amikacin resulted in increased intracellular activity against one, two, and four isolates, respectively). For the three-drug combinations, the combination of roxithromycin plus ethambutol used with rifampin or clofazimine was the most uniformly active against all five MAC isolates, with activity increases of 42 to 90%, followed by roxithromycin plus ethambutol used with amikacin, which resulted in activity increases of 15 to 90%. The overall level of intracellular killing after 5 days of drug addition, in comparison with growth in untreated controls, varied from 1 to 3 log units depending on the individual MAC isolate and/or drug combination used. PMID- 7786005 TI - Efficacies of ABT-719 and related 2-pyridones, members of a new class of antibacterial agents, against experimental bacterial infections. AB - The 2-pyridones are a new class of broad-spectrum orally bioavailable antibacterial agents. These compounds are potent bacterial DNA gyrase inhibitors which differ from fluoroquinolones by placement of the nitrogen atom in the ring juncture. ABT-719 is an S isomer and a representative 2-pyridone. ABT-719 administered orally or subcutaneously was 4- to 10-fold more effective than ciprofloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes infections in normal mice. ABT-719 was equivalent in efficacy to ciprofloxacin for treatment of gram-negative bacterial infections caused by Pseudomonas aeruginosa or Escherichia coli. The racemate and R forms of ABT-719 produced similar results against gram-positive and gram-negative bacterial infections. The 50% effective doses of ABT-719 were at least threefold lower than those of ciprofloxacin for therapy of intracellular infections caused by Salmonella typhimurium or Listeria monocytogenes. In immunosuppressed mice, ABT-719 was more effective than ciprofloxacin against quinolone-sensitive S. aureus, Enterococcus faecalis, and Enterococcus faecium. The pharmacokinetic properties of ABT-719 were consistent with its relative efficacy. The 2-pyridones are potent, orally available antibacterial agents with efficacy against gram positive and gram-negative bacterial infections in mice. PMID- 7786007 TI - Use of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil as a novel antiviral agent for hepatitis B virus and Epstein-Barr virus. AB - A novel anti-hepatitis B virus (anti-HBV) agent, 2'-fluoro-5-methyl-beta-L arabinofuranosyluracil (L-FMAU), was synthesized and found to be a potent anti HBV and anti-Epstein-Barr virus agent. Its in vitro potency was evaluated in 2.2.15 and H1 cells for anti-HBV and anti-Epstein-Barr virus activities, respectively. In vitro cytotoxicity in MT2, CEM, 2.2.15, and H1 cells was also assessed, and the results indicated high antiviral selectivities of L-FMAU in these cells. PMID- 7786009 TI - Pneumococcal resistance in southwest Virginia. AB - Resistance patterns of Streptococcus pneumoniae in southwest Virginia were determined for 100 consecutive, hospital-based isolates, mostly from adults. Oxacillin disk screening identified all resistant isolates. Sixteen percent of the isolates were penicillin resistant (10% were highly resistant). E-strip testing revealed the following MICs (in micrograms per milliliter, with percentages of isolates in parentheses): cefotaxime, < or = 0.5 (92%); ceftriaxone, < or = 0.5 (95%); ceftizoxime, < or = 0.5 (85%); erythromycin, < or = 1 (87%); ofloxacin, < or = 2 (80%); vancomycin, < or = 1 (98%). PMID- 7786008 TI - Revised interpretation of oxacillin MICs for Staphylococcus epidermidis based on mecA detection. AB - In 1992 and 1993, at The Ohio State University Medical Center, a larger proportion of Staphylococcus epidermidis strains required oxacillin MICs of 1 to 2 micrograms/ml than did Staphylococcus aureus strains. mecA genotype was correlated with antimicrobial susceptibility for selected clinical S. epidermidis strains. All 14 strains that required oxacillin MICs of < or = 0.25 microgram/ml and 2 of 5 strains that required oxacillin MICs of 0.5 microgram/ml were susceptible by 1-microgram oxacillin disk test and were mecA negative. Three of 5 strains that required oxacillin MICs of 0.5 microgram/ml and all 18 strains that required oxacillin MICs of > or = 1.0 microgram/ml were resistant by oxacillin disk test and were mecA positive. Current National Committee for Clinical Laboratory Standards MIC interpretive criteria may underestimate methicillin resistance among S. epidermidis strains. PMID- 7786010 TI - In vitro activity of a new fluoroquinolone, CP-99,219, against strains of Neisseria gonorrhoeae. AB - The susceptibilities of 216 strains of Neisseria gonorrhoeae to a new fluoroquinolone, CP-99,219 were determined. For strains for which the MICs of ciprofloxacin were < or = 0.06 microgram/ml, the MICs at which 90% of the isolates are inhibited (MIC90s) of CP-99,219, ciprofloxacin, and ofloxacin were 0.008, 0.015, and 0.03 microgram/ml, respectively. For strains for which the MICs of ciprofloxacin were 0.125 to 0.5 microgram/ml, the MIC90s of CP-99,219, ciprofloxacin, and ofloxacin were 0.06, 0.25, and 0.5 microgram/ml, respectively. For strains for which the MICs of ciprofloxacin and ofloxacin were 2.0 micrograms/ml, the MIC of CP-99,219 was 0.25 microgram/ml. PMID- 7786011 TI - Comparative in vitro activities of L-695,256, a novel carbapenem, against gram positive bacteria. AB - The in vitro activity of a prototype 2-aryl carbapenem, L-695,256, against gram positive bacteria was examined. All streptococci and oxacillin-susceptible and resistant staphylococci were inhibited at concentrations of < or = 0.125, < or = 0.125, and 4 micrograms/ml, respectively. The activity of L-695,256 was superior to that of imipenem against other organisms intrinsically resistant to beta lactams. PMID- 7786012 TI - Treatment of murine pulmonary blastomycosis with SCH 51048, a broad-spectrum triazole antifungal agent. AB - The in vitro and in vivo activities of a new broad-spectrum triazole derivative, SCH 51048, against Blastomyces dermatitidis were evaluated. As determined by using the new National Committee for Clinical Laboratory Standards proposed standard for susceptibility testing of yeasts, SCH 51048 was the most active of the four agents tested in vitro against 13 strains of B. dermatitidis. In a well described murine model of acute pulmonary blastomycosis, SCH 51048 was comparable to amphotericin B and at least 30 times more active than itraconazole. On the basis of these experiments, clinical evaluation of SCH 51048 for the use in treatment of human blastomycosis should proceed. PMID- 7786013 TI - Chloroperoxidase-catalyzed benzylic hydroxylation. AB - Chloroperoxidase oxidizes p-methylanisole and p-ethylanisole to 4-methoxybenzyl alcohol and 1-(4'-methoxyphenyl)ethanol, respectively. It ineffectively oxidizes toluene to benzyl alcohol but does not appear to oxidize toluene substituted with strong electron-withdrawing groups. O-Demethylation is also observed. The enzyme is sensitive to substituents at other than the para position and does not detectably catalyze benzylic hydroxylation of p-methylanisole if it bears additional methyl or methoxy groups. An exception is 1,2-(methylenedioxy)-4 methylbenzene, which is oxidized to both 3,4-(methylenedioxy)benzyl alcohol and 2 hydroxy-4-methylphenol. Studies with H2(18)O2 indicate that all the oxygen incorporated into the product in the oxidation of p-methylanisole to 4 methoxybenzyl alcohol derives from the peroxide. The mono- and dideuterated methyl analogues of p-methylanisole are oxidized with apparent intramolecular isotope effects of 3.51 and 3.34, respectively. Abstraction of a hydrogen from a carbon bearing a hydroxyl group competes effectively with benzylic oxidation because 2-[1,1-2H2]phenylethanol is oxidized to 2-[1-2H]- rather than 2-[1,2 2H2]phenylacetaldehyde. Aldehyde formation therefore involves abstraction of the carbinol hydrogen rather than hydrogen migration to a benzylic carbocation intermediate. Chloroperoxidase resembles cytochrome P450 in that it catalyzes benzylic hydroxylation reactions but it has a more limited substrate specificity. PMID- 7786014 TI - Tyrosine modification by reactive nitrogen species: a closer look. AB - Peroxynitrite (ONOO-) is a powerful oxidant and cytotoxic species formed by the rapid reaction between nitrogen monoxide (nitric oxide, .NO) and superoxide (O2. ). At neutral pH ONOO- is partly protonated and this protonated form, peroxynitrous acid (ONOOH), decomposes rapidly to nitrate, forming (an) intermediate(s) with reactivity similar to .OH and .NO2. Peroxynitrite can hydroxylate and nitrate aromatic rings, and aromatic nitration of phenols such as tyrosine by ONOOH is proposed to proceed via a radical mechanism, with intermediate formation of .NO2. Modification of tyrosine by .NO2 also involves nitration via a radical mechanism. Aromatic nitration of phenols by ONOO- has been shown to be enhanced by superoxide dismutase or Fe(3+)-EDTA, which were proposed to catalyze heterolytic cleavage of ONOOH to form a nitrating species similar to the nitronium ion (NO2+). We investigated possible mechanisms of tyrosine modification by various reactive nitrogen species, including ONOO-, 3 morpholinosydnonimine (SIN-1), and .NO2. Reaction of tyrosine with ONOO- leads to formation of 3-nitrotyrosine and dityrosine, indicating intermediate formation of tyrosyl radicals. The pH dependence of formation of both 3-nitrotyrosine and dityrosine by ONOO- suggests that intermediate formation of ONOOH is required. Qualitatively similar results were obtained when ONOOH was generated continuously by H2O2 and NaNO2 at mildly acidic pH or with SIN-1, a compound which at neutral pH releases both .NO and O2.-, presumably producing ONOO-. However, relatively low yields of nitrotyrosine were obtained with SIN-1, possibly because of competing reactions of tyrosyl radicals with .NO or O2.-. Possible involvement of .NO2 in tyrosine modification by ONOO- was studied using hydroxyl radical scavengers, which can increase the radical yield during decomposition of ONOOH and thereby enhance generation of .NO2. Hydroxyl radical scavengers did not affect tyrosine modification by .NO2 directly and slightly inhibited tyrosine modification by authentic ONOO-. However, when ONOO- was produced at a slower rate, either by SIN-1 or by H2O2/NaNO2 at acidic pH, hydroxyl radical scavengers were found to significantly enhance tyrosine nitration. Our results suggest that ONOO- or ONOO(-)-generating systems induce nitration of tyrosine (or tyrosine residues in proteins) via intermediate formation of tyrosyl radicals and .NO2. PMID- 7786016 TI - Inhibition of glycosylation by amphomycin and sugar nucleotide analogs PP36 and PP55 indicates that Haloferax volcanii beta-glucosylates both glycoproteins and glycolipids through lipid-linked sugar intermediates: evidence for three novel glycoproteins and a novel sulfated dihexosyl-archaeol glycolipid. AB - Arachaebacteria have been recently placed in evolution as a separate kingdom of organisms between procaryotes and eucaryotes. Although these organisms contain both glycolipids and glycoproteins, they possess no Golgi. No biosynthetic work has been published on the complex carbohydrates of these newly reassigned organisms. This report describes preliminary results from one member of this kingdom, Haloferax volcanii, which suggest that all glycosylation proceeds through lipid intermediates. Evidence for novel glycolipid structure was also found during this study. H. volcanii plasma membranes contain all of the enzyme activities for synthesis of N-linked glycoproteins and archaeol-based glycolipids. For glucose transfer, all reactions apparently proceed through glucose-phosphopolyisoprenol using UDP-glucose as primary donor. Incorporation of D-[3H]glucose from UDP-D-[3H]glucose into glycoproteins and glycolipids of H. volcanii was stimulated by addition of C55-polyisoprenol phosphate, but not by C85-105 dolichol phosphate, and was inhibited by amphomycin and two recently described sugar nucleotide analogs, PP36 (5'-[N-(2-decanoylamino-3-hydroxy-3 phenylpropyloxy carbonyl)glycyl]amino]-5'-deoxyuridine) and PP55 (5'-O-[[(2 decanoylamino-3-phenylpropyloxycarbonyl) amino]sulfonyl]uridine). All three inhibitors are reported to block transfer of sugar from UDP-sugars to phosphopolyisoprenols in eucaryotes. However, in H. volcanii these inhibitors apparently block transfer of glucose from polyprenyl intermediates to final glycoproteins and glycolipid products. The sulfodihexosyl archaeol glycolipid fraction was partially characterized by mass spectrometry and was found to contain a previously unreported structure with sulfate on the reducing-end sugar. Four major glycoproteins 190, 105, 56, and 52 kDa and an archaeol-based glycolipid fraction were labeled by amphomycin-sensitive pathways. Photoaffinity labeling of H. volcanii homogenate with 5-azido-[32P]UDP-Glc tagged only one 45 kDa polypeptide which is a probable glucosyl-phosphorylpolyisoprenol synthase. The fact that only one polypeptide band was photoaffinity-labeled indicated that no other transferase utilized UDP-glucose directly in H. volcanii. The salt requirement of the UDP-glucose-dependent pathways suggests that cytoplasmic enzymes function in a high salt environment in H. volcanii. The archaebacterial plasma membrane thus expresses many functions for glycosylation of both glycoproteins and glycolipids, normally found in the endoplasmic reticulum and Golgi of eucaryotes. PMID- 7786015 TI - Metabolic inhibition of cardiomyocytes causes an increase in sarcolemmal fluidity which may be due to loss of cellular cholesterol. AB - We examined whether metabolic inhibition (5 mM NaCN + 10 mM 2-deoxyglucose) affects sarcolemmal fluidity in cultured neonatal cardiomyocytes. As a measure of sarcolemmal fluidity we determined the fluorescence steady-state anisotropy (rss, which is reciprocally related to membrane fluidity) of cardiomyocytes labeled with 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene, p-toluenesulfonate. During metabolic inhibition, membrane fluidity increased progressively: after 30 min rss had fallen by 6.7 +/- 1.2% (mean +/- SE; n = 9; P < 0.05) compared to baseline values, and after 90 min by 14.5 +/- 3.5% (P < 0.05; n = 5). Beyond 90 min rss did not decrease any further. During control incubations (without metabolic inhibition), no significant changes in rss were observed. During metabolic inhibition cellular free cholesterol content declined: after 30 min free cholesterol content had decreased by 12.2 +/- 3.1% (P < 0.02; n = 4), compared to baseline values, and after 90 min by 31.1 +/- 8.3% (P < 0.02; n = 4). We conclude that metabolic inhibition induces an increase in sarcolemmal fluidity, which may be caused by a decrease in sarcolemmal free cholesterol content. PMID- 7786017 TI - Limited proteolysis of S-adenosylhomocysteine hydrolase: implications for the three-dimensional structure. AB - S-Adenosylhomocysteine (AdoHcy) hydrolase was subjected to limited proteolytic digestion utilizing the proteases trypsin, V8, and papain. Results of the trypsin digest revealed one major susceptible peptide bond between amino acid residues 103 and 104 which is most likely exposed to solvent. Binding of the substrate adenosine substantially reduced the susceptibility of this site, indicating that this peptide bond may be located at or near the substrate binding site. Wild-type AdoHcy hydrolase (which exists as a tetramer) was completely resistant to V8 digestion, while a site-directed mutant form (in which Lys at position 426 was changed to Glu) of the enzyme that exists primarily as a monomer had one major V8 protease cleavage site between amino acid residues 198 and 199, suggesting that these two amino acid residues may be positioned within the tetramerization region of each subunit. Limited papain digestion of AdoHcy hydrolase revealed that the enzyme, despite multiple peptide bond cleavages, was able to maintain its quaternary structure and remain catalytically functional. This observation suggests that AdoHcy hydrolase exists as a very compact enzyme with extensive intramolecular bonding. Identification of a surface-exposed peptide bond and one located in the tetramerization domain of each subunit may provide some constraints on how each subunit can be oriented in space. Results from this study support a previously described model (D. B. Ault-Riche, C. S. Yuan, and R. T. Borchardt (1994) J. Biol. Chem., 269, 31, 472-31, 478) in which the formation of the active site is dependent upon proper quaternary structure and also suggest that the active site of the enzyme may be located at or near the tetramerization domain of each subunit. PMID- 7786019 TI - Glycosaminoglycan addition to proteoglycans by articular chondrocytes--evidence for core protein-specific pathways. AB - The intracellular compartmentalization of enzyme activities involved in the elongation and sulfation of glycosaminoglycans on aggrecan, decorin, and fibromodulin was investigated using brefeldin A, a compound with known inhibitory action on normal vesicular transport and secretion of macromolecules. Treatment of bovine chondrocyte cultures with the compound resulted in greater than 98% inhibition of Na35SO4 incorporation into macromolecules, whereas [3H]leucine or [3H]glucosamine continued at 60-70% of the levels measured in control cultures. The release of newly synthesized products into the medium was also decreased markedly by brefeldin A to 7 and 2% of control levels for [3H]leucine- and [3H]glucosamine-labeled macromolecules, respectively. Analysis of [3H] glucosamine-labeled products in these cultures showed that synthesis of sulfated glycosaminoglycans (chondroitin/dermatan sulfate and keratan sulfate) was inhibited in response to brefeldin A, whereas hyaluronan synthesis was essentially unaffected. Significant amounts of elongated chondroitin continued to be synthesized in the presence of brefeldin A. Immunoprecipitation of [3H]leucine labeled decorin, aggrecan, and fibromodulin from cells showed that aggrecan and fibromodulin were not substituted with glycosamino-glycans, whereas all decorin molecules synthesized under these conditions were substituted with chondroitin. The results suggest that in articular chondrocytes, elongation of the glycosaminoglycan chains on decorin, but not their sulfation, occurs in a Golgi compartment unaffected by disruption of vesicular core protein transport. This is in contrast to glycosaminoglycan elongation and sulfation on aggrecan and fibromodulin, where both processes apparently occur in the trans-Golgi network, which becomes inaccessible to these core proteins in the presence of brefeldin A. The results further suggest that in brefeldin A-treated cells decorin is contained in a discrete ER-Golgi compartment separated from aggrecan; this compartment is accessible to p-nitrophenyl-beta-D-xylosides, since beta-xylosides become elongated with chondroitin even in the presence of brefeldin A. PMID- 7786020 TI - Identification and distribution of peptide:N-glycanase (PNGase) in mouse organs. AB - A wide occurrence of peptide:N-glycanase (PNGase) in mouse organs was demonstrated. PNGase activities were determined using 14C-labeled fetuin glycopeptide I as a substrate by a newly improved enzyme assay based on the paper chromatographic and paper electrophoretic analyses. PNGase activities were detected in both soluble and membranous (or particulate) fractions, although the levels of the activities were different from organ to organ. Soluble PNGases were partially purified from brain, liver, kidney, and spleen by TSK butyl-Toyopearl 650 M hydrophobicity chromatography and characterized for enzymatic properties. The soluble enzymes were found to share the following properties: (a) high hydrophobicity; (b) sensitivity to metal cations such as Zn2+, Cu2+, and Fe3+; and (c) requirement of sulfhydryl group(s) for enzyme activity. Notably, soluble PNGases were unable to degrade glycoasparagine substrates and the optimal pH was near 7.0, suggesting that they were not lysosomal enzymes, but perhaps being involved in basic biological processes in certain intracellular nonlysosomal events. All of these enzymatic properties found for mouse organ-derived PNGases were the same as those recently found for L-929 PNGase that was highly purified as a soluble enzyme from mouse fibroblast L-929 cells (Suzuki, T., Seko, A., Kitajima, K., Inoue, Y., and Inoue, S. (1994) J. Biol. Chem. 269, 17611-17618. PMID- 7786018 TI - A new cytochrome P450 form belonging to the CYP2D in dog liver microsomes: purification, cDNA cloning, and enzyme characterization. AB - A new form of cytochrome P450 (P450 DUT2) was purified from untreated male dog liver microsomes. The final preparation (a specific content of 19.1 nmol P450/mg protein) showed a single band with an apparent monomeric molecular weight of 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but was further separated into two apoproteins (P450 DUT2a and P450 DUT2b) by reverse phase HPLC. Both proteins had identical NH2-terminal amino acid sequences, but the first three amino acids of P450 DUT2b were truncated in P450 DUT2a. Purified P450 DUT2 showed 5 to 18 times higher catalytic activities than did hepatic microsomes toward desipramine, metoprolol, and dextromethorphan. These activities in dog liver microsomes were strongly inhibited by anti-P450 DUT2-IgG. A 1.7 kilobase pair cDNA (cDUT2) encoding a male dog liver P450 of 500 amino acid residues (molecular weight 56,400) was isolated and sequenced. The first 35 NH2 terminal amino acid sequence of P450 DUT2b coincided with the deduced amino acid sequence of cDUT2 at 2-36. The deduced total amino acid sequence of cDUT2 shared high similarity with the reported 2D forms (with 2D6, 74.6%; 2D14, 75.4%; 2D1, 65.4%; and 2D9, 63.6%). Moreover, the expressed P450 DUT2 in COS-7 cells had catalytic activities similar to those of purified P450 DUT2. Therefore, this paper is the first report about dog CYP2D. Furthermore, Northern and Western blot analyses indicated that the expressed levels of mRNA and protein were almost equal between male and female dogs. Western blot analysis suggested that P450 DUT2 is a constitutive and major (approximately 20% of the total P450) form, indicating that the 2D subfamily P450 in dog liver is quite unique from CYP2D members of other species. PMID- 7786022 TI - A calorimetric study of binary mixtures of 1-octadecanoyl-2-decanoyl-sn-glycero-3 phosphoethanolamine and dimyristoyl phosphatidylethanolamine. AB - Model membranes composed of 1-octadecanoyl-2-decanoyl-sn-glycero-3- phosphoethanolamine and dimyristoyl phosphatidylethanolamine have been studied calorimetrically. 1-Octadecanoyl-2-decanoyl-sn-glycero-3- phosphoethanolamine is a highly asymmetric mixed-chain lipid, whereas dimyristoyl phosphatidylethanolamine is an identical-chain lipid with the same molecular weight. Calorimetric results indicate that these two lipids with a common molecular weight are completely miscible in the two-dimensional plane of the lipid bilayer in the liquid-crystalline state and that they are only partially miscible in the gel-state bilayer. Specifically, binary mixtures of these two lipids form eutectic phase diagrams at pH 7.4 and 10.0. PMID- 7786021 TI - Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: further insights into the role nitric oxide plays in oxidative stress. AB - Endogenously formed nitric oxide (NO) possesses diverse properties such as regulating physiological functions, exerting specific toxic effects, and protecting against various toxic substances. Recent studies suggest that in the presence of reactive oxygen species, NO can serve as an antioxidant. We show here that NO delivered from the NO donor compound, PAPA/NO (NH2(C3H6)(N[N(O)NO](C3H7)), protects Chinese hamster V79 lung fibroblasts from the cytotoxicity of t-butyl hydroperoxide and cumene hydroperoxide. In contrast, the other end products of PAPA/NO degradation in aqueous solution, NH2(C3H6)NH(C3H7) and nitrite, did not protect. The NONOate DEA/NO releases NO six times faster than PAPA/NO, yet did not afford protection, which implies that NO must be present throughout the alkyl hydroperoxide exposure. Measurements of NO concentrations released from PAPA/NO suggest that micromolar levels protect against cytotoxicity induced by alkyl hydroperoxides. These findings demonstrate that the flux of NO sustained over the duration of the peroxide exposure determines protection and not the total of NO delivered. These results suggest that concentrations of NO produced in the microenvironment of endothelial cells are high enough to protect cells from Fenton-type-mediated toxicity and support the premise that NO may exert a salutary effect in certain diseases associated with membrane damage. PMID- 7786023 TI - Purification and characterization of human serum N-acetylglucosamine-1 phosphodiester alpha-N-acetylglucosaminidase. AB - Many lysosomal enzymes are recognized and selected by a unique marker in the form of mannose 6-phosphate groups which are present exclusively on their N-linked oligosaccharides. Two enzymes act sequentially to catalyze the addition of mannose 6-phosphate groups to the proteins: N-acetylglucosamine phosphotransferase (GlcNAc phosphotransferase) and N-acetylglucosamine-1 phosphodiester alpha-N-acetylglucosaminidase (phosphodiester alpha-GlcNAcase). We report here the purification and partial characterization of phosphodiester alpha GlcNAcase from human serum. The enzyme was purified over 600,000-fold by utilizing ammonium sulfate precipitation, fractionation on wheat germ agglutinin Sepharose, Fe(3+)-chelating Sepharose, and Cu(2+)-chelating Sepharose, and renaturation from gel slices after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The protein observed after renaturation and subsequent SDS-PAGE and silver staining had an apparent molecular mass of 118 kDa, which is slightly smaller than bovine liver phosphodiester alpha-GlcNAcase (Mullis et al. (1994) J. Biol. Chem. 269, 1718-1726). Serum enzyme activity does not require Triton X-100 and is not stimulated by its addition. These results suggest that the enzyme found in serum represents a form secreted after proteolysis in the Golgi of the membrane-bound enzyme. The serum enzyme hydrolyzed UDP-GlcNAc to UDP and GlcNAc and hydrolyzed GlcNAc-P-Man alpha Me into alpha MeMan-P and GlcNAc. The enzyme had no hydrolyzing activity toward UDP GalNAc, UDP-Glc, [6-3H]GlcNAc beta 1-3Gal beta 1-4Glc, p-nitrophenyl-alpha-N- acetylglucosaminide, p-nitrophenyl-beta-N-acetylglucosaminide, p-nitrophenyl alpha-N-galactopyranoside, or p-nitrophenyl-beta-N- galactopyranoside. The enzyme activity was strongly inhibited by UDP-GlcNAc and GlcNAc-1-phosphate, had a pH optimum between pH 6.0 and 7.0, and was inhibited by FeCl3, FeSO4, and CuSO4. The Km values for UDP-GlcNAc and GlcNAc-P-Man alpha Me were 0.94 and 0.45 mM, respectively. Over 77% of enzyme activity remained after incubation for 10 min at 70 degrees C, demonstrating an unusual thermostability of the serum enzyme. PMID- 7786024 TI - Isolation and characterization of Cajanus cajan lectin. AB - Cajanus cajan lectin was isolated by ammonium sulfate fractionation and affinity chromatography on an IgM-Sepharose 6B column. Gel filtration and SDS-PAGE showed size homogeneity of the lectin. The lectin with M(r) 18,000 on SDS-PAGE had gel filtration behavior which was consistent with a molecular weight of 39 kDa and a Stokes radius of 2.74 nm. The results showed that the lectin is a dimer composed of identical subunits with N- and C-terminal residues of threonine and alanine, respectively. The glycoprotein lectin contained 3% concanavalin A-reactive neutral carbohydrates. Its amino acid composition is characterized by high contents of acidic amino acids. The number of tyrosine and tryptophan residues per mole of the lectin was determined to be 14 and 4, respectively, by spectrophotometry. Results on the effects of large numbers of saccharides on lectin-mediated hemagglutination and lectin-IgM precipitation showed that the C. cajan lectin was specific for mannose and glucose. A comparative study of the properties of C. cajan lectin and concanavalin A is also presented. PMID- 7786025 TI - Modulation of 2-oxoglutarate dehydrogenase and oxidative phosphorylation by Ca2+ in pancreas and adrenal cortex mitochondria. AB - The effect of external free Ca2+ ([Ca2+]ex) on the 2-oxoglutarate dehydrogenase (2-OGDH) activity and the rate of state 3 respiration was studied in dog pancreas and adrenal cortex mitochondria. A method for the preparation of mitochondria from pancreas, free of zymogen granules, was developed. The mitochondria showed high respiratory control values and maintained adequate ADP/O ratios in the course of several hours. Half-maximal stimulation (K0.5) of 2-OGDH activity and state 3 respiration by Ca2+ was decreased twofold by spermine, in both pancreas and adrenal cortex mitochondria incubated with Mg2+; Na+ increased the K0.5 value for Ca2+ in both kinds of mitochondria. The matrix Ca2+ content was enhanced by spermine at different [Ca2+]ex. The Ca2+ gradient ([Ca2+]m/[Ca2+]ex) determined in Fluo 3-loaded pancreas mitochondria was found to be below 1, either in the presence of Na+ or in the absence of spermine. The protonmotive force was increased by 1 microM Ca2+, in state 3 conditions, by 6-8 mV; lower Ca2+ concentrations kept the H+ gradient rather constant. An increase in the spermine/Mg2+ ratio at constant external Ca2+ resulted in stimulation of the 2 OGDH activity and state 3 respiration. The data indicate that matrix Ca2+ may regulate the rate of ATP synthesis in pancreas and adrenal cortex mitochondria, through the modulation of 2-OGDH and the maintenance of a high H+ gradient. In addition to changes in external Ca2+, the variation in the spermine/Mg2+ ratio may also exert control of oxidative phosphorylation. PMID- 7786026 TI - Interaction of retinoblastoma gene product with transcription factors ATFa and ATF2. AB - Two highly related transcription factors, activating transcription factors a and 2 (ATFa and ATF2) are able to activate expression in CHO cells of a reporter gene driven by the human transforming growth factor beta 2 gene promoter. This action is dependent on the intact motif CGTCA which is found as part of the cAMP responsive element in a number of promoters and to which both factors can bind in vitro. The retinoblastoma gene product also weakly stimulates expression of this reporter gene but, in combination with the factors, it exhibits a differential action: additive or greater stimulatory effects with ATF2 but strong inhibition of the actions of ATFa. Thus, although both of these two related factors are able to exert the same apparent effect on this promoter, coexpression of the retinoblastoma gene product reveals at least one significant difference in their actions. PMID- 7786027 TI - Food restriction stimulates conjugation of p-nitrophenol in perfused rat liver. AB - Rates of conjugation of p-nitrophenol were studied in livers from normal and food restricted rats perfused with either p-nitroanisole or p-nitrophenol. Female Sprague-Dawley rats had ad libitum access to a Purina 5001 nonpurified diet (control) or were given 65% of the intake of controls for 3 weeks. Livers were perfused with oxygenated Krebs-Henseleit buffer using a nonrecirculating system. Maximal rates of conjugation of p-nitrophenol, generated either from the O demethylation of p-nitroanisole (200 microM) or from the infusion of p nitrophenol (70 microM), were elevated significantly nearly twofold by food restriction. Thus, food restriction stimulates conjugation in the intact liver cell. Specifically, rates of conjugation were increased from 2.1 +/- 0.2 to 3.7 +/- 0.4 and from 3.3 +/- 0.6 to 5.8 +/- 0.5 mumol/g/h when 200 microM p nitroanisole or 70 microM p-nitrophenol were infused, respectively. On the other hand, rates of conjugation were not affected by food restriction when low concentrations of p-nitroanisole (50 microM) or p-nitrophenol (20 microM) were infused. Further, food restriction did not alter rates of conjugation in isolated microsomes supplemented with excess UDPGA. Interestingly, both UDP-glucose and UDP-glucuronic acid were increased significantly in liver extracts from food restricted rats when livers were perfused with high but not low concentrations of p-nitrophenol. Under these conditions, the increase in UDP-glucuronic acid was threefold. Moreover, food restriction increased carbohydrate release from the liver about twofold. Glycogen content was also increased significantly in liver extracts from 8.4 +/- 1.9 to 60.4 +/- 13.8 mmol/kg wet weight by food restriction. Taken together, these data support the hypothesis that food restriction stimulates conjugation of p-nitrophenol concentrations by increasing the supply of the pivotal cofactor UDP-glucuronic acid from carbohydrate reserves (e.g., glycogen). PMID- 7786028 TI - 9-cis-retinoic acid selectively activates the cellular retinoic acid binding protein-II gene in human neuroblastoma cells. AB - Two families of nuclear retinoid receptors, retinoic acid receptor and retinoid X receptor (RAR and RXR respectively), and a family of cellular retinoic acid binding proteins (CRABPI and II) participate in the retinoic acid (RA) signaling pathway. The presence and function of many of these receptors and cellular binding proteins have not been fully explored in RA-responsive human neuroblastoma cells. We have previously shown that RAR transcripts and protein are present in human neuroblastoma cells, and that all-trans RA induces the expression of the RAR beta mRNA. In this paper, we demonstrate that human neuroblastoma cells express mRNA for RXR alpha and beta. The mRNA for CRABPI is present in untreated human neuroblastoma cells, whereas the mRNA for CRABPII is induced in cells treated with either all-trans RA or 9-cis RA. Furthermore, 9-cis RA, a ligand that binds to both the RAR and the RXR families, selectively activates the CRABPII gene. In contrast, all-trans RA and 9-cis RA are equally effective in the induction of RAR beta transcript and inhibition of cell proliferation. Since both retinoids inhibit human neuroblastoma cell proliferation, it appears that induction of RAR beta rather than of CRABPII is more likely linked to the regulation of human neuroblastoma cell growth. PMID- 7786030 TI - The DNA binding of purified Ah receptor heterodimer is regulated by redox conditions. AB - The Ah receptor from rat liver has been purified, using a specific oligonucleotide affinity column, in order to characterize the components of the receptor and to investigate features that modulate its DNA-binding activity. The purified DNA-binding form of rat Ah receptor contains three major components, with estimated molecular masses of 108, 98, and 96 kDa. Antibodies to two peptides from the mouse Ah receptor bind the 108-kDa protein, but not the 98-kDa protein, and bind weakly at the position of the 96-kDa protein. The sequences of four peptides from samples containing both the 96- and 98-kDa proteins are all highly similar to segments of the human Ah receptor nuclear translocator (Arnt) protein. Antibodies to a peptide from the human Arnt protein bind the 96- and 98 kDa proteins, but not the 108-kDa protein. These data show that the Ah receptor itself and two forms of the Arnt protein are the major components of the purified DNA-binding form of receptor. In gel shift assays the purified receptor forms two specifically bound complexes with a xenobiotic responsive element (XRE), which may correspond to Ah receptor heterodimers with either of the two forms of Arnt protein. The DNA binding of the purified heterodimer is substantially decreased under oxidizing conditions. Oxidation inhibits receptor DNA binding without greatly altering the size of the purified heterodimer. This sediments at 5.9S in its reduced form and at 6.5S in its oxidized form. Dithiothreitol restores the XRE binding of oxidized receptor, with similar effects on both of the receptor XRE complexes. In the presence of nuclear extract, reduced thioredoxin also restores the XRE binding of oxidized receptor. PMID- 7786029 TI - Detection of hydroxyl radicals upon interaction of ozone with aqueous media or extracellular surfactant: the role of trace iron. AB - As part of a study on mechanisms modulating ozone-induced surfactant perturbations, we used the electron paramagnetic resonance (EPR) spin trapping technique to determine the type and origin of radicals generated following interaction of ozone with aqueous solutions and cell-free bronchoalveolar lavage fluid (BAL) fractions. All aqueous media were exposed to ozone at 25 degrees C with or without added chelator, 1 mM diethylenetriaminepentaacetic acid, and spintrap, 100 mM 5,5'-dimethyl-1-pyrroline-1-oxide (DMPO). Exposure of distilled water to 0.5, 1.0, 2.0, and 3.0 ppm ozone for 1 h yielded four-line spectra, 1:2:2:1, consistent with hydroxyl radical adduct formation (DMPO-OH), the amplitudes of which increased with the ozone concentration. No signals were obtained from air-exposed samples. Similar four-line spectra were also produced following interaction of 3 ppm ozone with Hank's balanced salt solution (HBSS) alone or containing BAL fractions. Addition of the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) to the incubation medium strongly inhibited formation of DMPO-OH adduct during ozone exposure. As an alternate method of demonstrating the generation of hydroxyl radicals, aqueous solutions of 1 mM L-phenylalanine were exposed to high concentrations of ozone and shown, using ion-exchange chromatography, to contain small amounts of L-tyrosine. Production of hydroxyl radicals upon interaction of ozone and water was further substantiated using the spintrap PBN (phenyl-N-tert-butylnitrone) in the presence of DMSO which reacts with the hydroxyl radical resulting in the formation of methyl radical. The methyl radical subsequently reacts with spintrap PBN, yielding PBN-methyl adduct. In the absence of DMSO there was no detectable formation of methyl radical adduct. EPR double distilled water containing DMPO showed a small amount of DMPO OH adduct upon exposure to ozone. Addition of 10 microM ferrous sulfate to this mixture produced a 10-fold increase of the signal, which was attenuated in the presence of 1500 U catalase, strongly attenuated with 50-500 microM deferoxamine or 8000 U catalase and abolished by higher concentration of deferoxamine (1 mM). The signal was not influenced by 1000 U superoxide dismutase. These results indicate that hydroxyl radicals are produced via iron-dependent reactions during the initial interaction of ozone with aqueous media, including bronchoalveolar fluid. PMID- 7786032 TI - Kinetics of cytochrome c2+ oxidation by peroxynitrite: implications for superoxide measurements in nitric oxide-producing biological systems. AB - Cytochrome c3+ has been extensively used for the detection of superoxide produced in biological systems due to its fast superoxide-mediated reduction to cytochrome c2+. However, another biomolecule which is sometimes cogenerated with superoxide, nitric oxide, reacts with superoxide at almost diffusion-controlled rates (6.7 x 10(9) M-1 s-1), leading to the production of a highly oxidizing species, peroxynitrite anion (ONOO-). In this work we report that peroxynitrite readily oxidizes cytochrome c2+ to cytochrome c3+ in an ascorbate-reversible manner. The reaction between peroxynitrite and cytochrome c2+ occurs with a second-order rate constant of 2.3 x 10(5) M-1 s-1. The pH dependence of the apparent second-order rate constants as well as the effect of different scavengers indicated that peroxynitrous acid (ONOOH) in the ground state was the actual species responsible of cytochrome c2+ oxidation. The activation enthalpy, free energy, and entropy were +10.8 kcal mol-1, +11.8 kcal mol-1, and -3.15 cal mol-1 K-1, respectively, in agreement with the proposed reaction mechanism. Additionally, our results imply that when quantitating superoxide by the cytochrome c3+ reduction method, the existence of a simultaneous generation of nitric oxide and peroxynitrite may lead to an underestimation of the rates of superoxide production. PMID- 7786031 TI - Substrate specificity of human liver aldehyde oxidase toward substituted quinazolines and phthalazines: a comparison with hepatic enzyme from guinea pig, rabbit, and baboon. AB - Partially purified aldehyde oxidase (EC 1.2.3.1) has been prepared from human, rabbit, guinea pig, and baboon liver by heat treatment and precipitation with ammonium sulfate. The interaction of 35 substituted quinazolines and phthalazines with human liver enzyme has been studied using a spectrophotometric assay. Fifteen quinazoline and 14 phthalazine derivatives were found to be substrates for human liver aldehyde oxidase with Km values ranging from 5 to 500 microM. The substrate specificity of the quinazolines toward rabbit, guinea pig, and baboon liver aldehyde oxidase has also been investigated; the reaction of substituted phthalazines with mammalian liver enzyme has been reported previously (Beedham et al., 1990, Biochem. Pharmacol. 39, 1213-1221). Oxidation products of 2 substituted (4-substituted) quinazolines with rabbit liver aldehyde oxidase were identified by MS as 4-oxo (2-oxo)-quinazolines, respectively. In all cases, unsubstituted compounds gave the highest oxidation rates and the presence of lipophilic substituents presumably facilitated hydrophobic binding to the enzymes. However, there were marked differences in substrate specificity between human liver aldehyde oxidase and hepatic enzyme from rabbit, guinea pig, and baboon with the size of substrate being the differentiating factor. The molecular sizes of the substrates, estimated using calculated molar refractivities, ranked the size of the binding site of aldehyde oxidase in the order rabbit < guinea pig < baboon < man. Isoelectric points of the different aldehyde oxidase isozymes ranged from pH 5.10 for rabbit to 6.40 for the human liver isozyme. These results indicate that rabbit liver aldehyde oxidase shows marked differences from the human liver enzyme in its handling of quinazoline and phthalazine substrates. PMID- 7786033 TI - Purification and characterization of tubulin from parental and vincristine resistant HOB1 lymphoma cells. AB - A multidrug-resistant lymphoma cell line resistant to 1.0 microM vincristine (designated HOB1/VCR1.0) was established. The tubulins of parental and resistant cell lines were purified by ion-exchange chromatography. Two-dimensional polyacrylamide gel electrophoresis of tubulins showed a decrease in the basic component of beta-tubulin in the HOB1/VCR1.0 cell line; native isoelectric focusing of tubulins showed decreased expression of two more basic tubulin dimers in the same cell line. The [3H]vincristine-tubulin binding studies were performed by filtration and HPLC and displayed the tubulin of HOB1/VCR1.0 cells having a weaker binding affinity to vincristine than those of parental HOB1 and HOB1/VCR0.5 cells. The binding constant Ka of purified tubulin to vincristine, calculated from the slope of the Scatchard curve, for parental HOB1 cells was 5.6 x 10(6), and that for HOB1/VCR1.0 cells was 3.1 x 10(6). The Scatchard kinetics was also used to determine the binding ability of the purified tubulins to [3H]colcemid: the Kas for parental and HOB1/VCR1.0 cells were 3.9 x 10(5) and 2.0 x 10(5), respectively. The current study suggests that high-level resistant cells, HOB1/VCR1.0, tend to express fewer tubulin isoforms of stronger binding affinities to antimitotic agents; that is, they preserve weak drug-binding forms rather than produce additional species. This may be a mechanism for the cells to protect themselves from drug injury when the P-glycoprotein cannot efficiently pump out the agent of high concentration within the cells. PMID- 7786034 TI - 25-Hydroxy[26,27-methyl-3H]vitamin D3-3 beta-(1,2-epoxypropyl)ether: an affinity labeling reagent for human vitamin D-binding protein. AB - Vitamin D-binding protein (DBP) is primarily involved in the binding and transportation of vitamin D3 and its various metabolites to target organs and tissues. This is manifested by the ability of DBP to bind vitamin D3 and its metabolites with high affinity. In the present study we developed 25 hydroxyvitamin D3-3 beta-(1,2-epoxypropyl)ether (25-OH-D3-epoxide) as an affinity labeling reagent of human DBP (hDBP). Competitive radioligand binding assays of 25-OH-D3-epoxide with hDBP demonstrated that the binding affinity of this analog was similar to that of 25-hydroxyvitamin D3 (25-OH-D3). Incubation of 25 hydroxy[26(27)-3H]-vitamin D3-3 beta-(1,2-epoxypropyl)ether [[3H]25-OH-D3 epoxide] with hDBP covalently labeled the protein. When the incubation was carried out in the presence of a large excess of 25-OH-D3, labeling was removed completely. When human Cohn IV fraction, containing hDBP, was incubated with [3H]25-OH-D3-epoxide a single protein band, corresponding to hDBP, was labeled. Labeling was completely obliterated in the presence of a large amount of 25-OH D3. However, an equivalent amount of 7-dehydrocholesterol had no effect on labeling. These results demonstrated that [3H]25-OH-D3-epoxide most probably labeled the vitamin D sterol-binding domain of hDBP. PMID- 7786035 TI - Copper, zinc superoxide dismutase in Escherichia coli: periplasmic localization. AB - Cu,ZnSOD purified from Escherichia coli has been used to raise antibodies in rabbits. The resultant antiserum was found to recognize a single band on Western blots of SDS-polyacrylamide gel electropherograms, and that single band coincided with the position of the Cu,ZnSOD. Ultrathin sections of fixed E. coli were treated with the antibody followed by protein A bearing 10-nm gold particles. Electron microscopy revealed that Cu,ZnSOD was largely localized in the periplasm in polar bays. PMID- 7786036 TI - Growth inhibition and cell killing by N-methyl-N-nitrosourea: metabolic alterations that accompany poly(ADP-ribosyl)ation. AB - The effect of inhibition of poly(ADP-ribose) polymerase (PARP) on the growth arrest and cell killing induced by N-methyl-N-nitrosourea (MNU) was studied in L929 fibroblasts. Depletion of NAD and ATP preceded the cell killing by a 1-h exposure to 10 or 15 mM MNU. 3-Aminobenzamide (ABA), an inhibitor of PARP, spared the depletion of NAD and ATP and prevented the cell killing. With 5 mM MNU, a depletion of NAD was promptly reversed, and there was no loss of ATP and no cell death. Aphidicolin, a DNA polymerase inhibitor, prevented the restoration of NAD, with resulting depletion of ATP and death of the cells, effects that were prevented by ABA. Azide together with 2-deoxyglucose depleted ATP, followed by a loss of NAD and cell death, changes that occurred in the absence of DNA single strand breaks (DNA SSB). ABA prevented the depletion of NAD, but not that of ATP, nor the cell killing. MNU (2.5 mM) inhibited cell growth without effect on the viability of the cells. ABA potentiated the cell growth inhibition. Thus, inhibition of PARP potentiates cell growth inhibition by limiting DNA repair mechanisms. Alternatively, inhibition of the DNA repair response to more extensive DNA damage prevents cell killing. The ATP depletion caused by poly(ADP ribosyl)ation, rather than DNA SSB and the loss of NAD, is the more critical event in the cell killing. PMID- 7786037 TI - Redox imbalance at the start of each morphogenetic step of Neurospora crassa conidiation. AB - The conidiation process of Neurospora crassa is characterized by three morphogenetic steps: hyphal adhesion, aerial hyphal formation, and production of conidia. Total protein oxidation and specific enzyme oxidation coincided with an increased oxygen-dependent chemiluminescence and indicated the occurrence of a hyperoxidant state at the onset of all three morphogenetic steps. Oxidation of NAD(P)H and excretion of glutathione disulfide was detected at the start of hyphae adhesion. Here we show that NAD(P)H and glutathione redox imbalance also occurred at the beginning of aerial hyphal growth and just before formation of conidia in the isolated cell structures. An increased loss and oxidation of NAD(P)(H) and glutathione were detected with each morphogenetic transition. These results give further support to our proposal that a hyperoxidant state develops at the start of each of the three morphogenetic processes during N. crassa conidiation. PMID- 7786038 TI - Sea urchin ovoperoxidase: solubilization and isolation from the fertilization envelope, some structural and functional properties, and degradation by hatching enzyme. AB - The soft fertilization envelope (SFE) devoid of tyrosine-derived cross-links was isolated from the sea urchin Hemicentrotus pulcherrimus embryos fertilized in the presence of 2 mM aminotriazole, a reversible inhibitor of ovoperoxidase (OPO). Most of the component proteins including OPO were solubilized from SFE by the use of a buffer containing 10 mM EDTA. The solubilized OPO was purified by chromatographies on Sepharose CL-6B, DEAE-Sephacel, and Superose 12HR columns to apparent electrophoretical homogeneity with Mr 70,000. The enzyme accounts for at least 3% of the total FE by weight and 10% by gel densitometry. Partial amino acid sequences of three proteolytic fragments of OPO, accidentally including the distal and proximal His residues, revealed up to 84% homology to mammalian thyroid peroxidases, myeloperoxidases, and lactoperoxidases (LPO), but the N terminal sequence showed little homology to them. The uv-VIS absorption spectrum of OPO has a maximum at 279 nm, Soret band at 415 nm, and a small quartet at 490, 542, 580, and 642 nm. The tyrosine cross-link profile in the reaction products of the OPO/tyrosine/H2O2 system as analyzed by HPLC with uv and fluorescence detection was similar to those of LPO and HRPO, with dityrosine as the only major component. However, it is different from that of the HCl hydrolysate of normally hardened FE that has much higher contents of trivalent cross-links trityrosine and pulcherosine. This result reflects the difference in the accessibility of the substrates to the enzyme: free tyrosine and OPO in solution vs Tyr residues and OPO both immobilized in FE. The enzyme OPO was degraded limitedly by purified hatching enzyme (envelysin) after 24 h incubation to mainly a 47-kDa fragment with its 67% peroxidase activity retained. PMID- 7786039 TI - The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase. AB - We studied the effects of dietary calcium (Ca) restriction and excess vitamin D3 on tissue 25-hydroxyvitamin D-1-hydroxylase (1-OHase) and 1,25(OH)2D/25-OH-D-24 hydroxylase (24-OHase) activities in rats. Effects were studied in four groups of rats, with each group receiving one of the following diets: a control diet consisting of normal Ca and normal vitamin D3 (NC), NC plus excess (75,000 IU/week) vitamin D3 (NCT), low Ca and normal vitamin D3 (LC), or LC diet with excess vitamin D3 (LCT). Rats fed the low-Ca diets (LC and LCT) had elevated plasma parathyroid hormone (PTH) concentrations, increasing > 3-fold relative to rats fed the normal Ca diets. The elevated concentrations of PTH in LCT rats did not result in increased plasma 1,25-dihydroxycholecalciferol [1,25(OH)2D3] (NC = 115 +/- 7 pg/ml; LCT = 99 +/- 11 pg/ml). Plasma 1,25(OH)2D in LC rats, however, was increased significantly (615 +/- 110, P = < 0.001). There were no differences in either plasma Ca or phosphorus between the LC and LCT groups. Dietary Ca restriction led to an 18-fold stimulation in renal 1-OHase activity in LC rats (P = < 0.01), while 1-OHase in the LCT rats was marginally but significantly elevated 2.3-fold (P = < 0.05). The ability of PTH to downregulate renal 24-OHase and the 1,25-dihydroxyvitamin D receptor (VDR) during prolonged Ca restriction remained intact, irrespective of vitamin D status. Also, the metabolic clearance rate for 1,25(OH)2D3 was enhanced by feeding excess vitamin D3, which was likely a result of the substantial elevations in intestinal (25-fold) and renal (46 fold) 24-OHase activities in the LCT and NCT groups, respectively. These data indicate that calcium restriction accompanied by excess vitamin D3 is attended by impaired responsiveness of renal 1-OHase to PTH and enhanced metabolic clearance of 1,25(OH)2D. PMID- 7786040 TI - Expression of cytochrome P450 2D6 in Escherichia coli, purification, and spectral and catalytic characterization. AB - Cytochrome P450 (P450) 2D6 is the classic human liver debrisoquine 4-hydroxylase, the first human P450 for which genetic polymorphism was clearly demonstrated. We prepared 11 different constructs of P450 2D6, with modification at the N terminus, for expression in Escherichia coli with the vector pCW. These varied considerably in levels of expression of apo- and holoprotein, with the best yield being obtained in a system in which much of the N-terminal hydrophobic segment was removed. Production of holoprotein was highly dependent upon the addition of delta-aminolevulinic acid and FeCl3 to cultures, even though heme production should not be limiting in this system. The expressed protein was not tightly bound to the "heavier" membrane fraction but did not appear to behave as a soluble protein either. A purification strategy was developed involving fractional centrifugation, Triton X-114 phase separation, and flavodoxin affinity chromatography, which led to recovery of apparently electrophoretically homogeneous protein in good yield. Purified P450 2D6 had the expected N-terminal amino acid sequence and catalytic activities toward debrisoquine (4 hydroxylation) and bufuralol (1'-hydroxylation). The availability of a ready source of the recombinant protein should facilitate physical as well as functional studies and antibody production for other uses. PMID- 7786042 TI - A 55-kDa protein (p55) of the goat uterus mediates nuclear transport of the estrogen receptor. II. Details of the transport mechanism. AB - A 55-kDa protein (p55) that mediates the transport of the estrogen receptor (ER) from the cytoplasm to the nucleus has been purified to homogeneity from goat uterine cytosol. Using this pure protein, some of the aspects of the mechanisms associated with the transport of the ER to the nucleus have been elucidated. The mechanism of ER transport into the nucleus can be separated into two steps: the p55-mediated transport and binding of ER to the nuclear membrane, followed by an ATP-dependent, 14-kDa protein(s)-mediated translocation of ER into the nucleus. The p55 has inherent ATPase activity and it is proposed that the energy released during this ATP hydrolysis is utilized in the nuclear transport of the ER. PMID- 7786041 TI - A 55-kDa protein (p55) of the goat uterus mediates nuclear transport of the estrogen receptor. I. Purification and characterization. AB - A 55-kDa protein (p55), purified from the goat uterine cytosol, transports estrogen receptor (ER) into the nucleus. Selective elution of this protein from a column of estrogen receptor-Sepharose using buffers containing high concentrations of lysine and the high affinity with which it binds to poly-L lysine-Sepharose indicate that it recognizes a lysine-rich region in the ER. Its strong binding to tubulin-Sepharose and actin-Sepharose is indicative of a role that the cytoskeletal elements play in the nuclear transport of the ER, mediated by p55. This protein can be purified in a single step following chromatography of the uterine cytosol on a column of actin-Sepharose. Antibodies raised against poly-L-aspartic acid cross-reacted with p55 and inhibited the nuclear transport of the ER. The binding of p55 to a heterologous nuclear localization sequence of the SV40 large T suggests that it may also be involved in the transport of proteins other than the ER. PMID- 7786043 TI - Detection of short-lived free radicals by low-frequency electron paramagnetic resonance spin trapping in whole living animals. AB - We report the direct observation of sulfur trioxide anion free radical (SO3.-) from the body of live mice by using a low-frequency (1.2 GHz, L-band) EPR spin trapping method. Intraperitoneal injection of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (15 mmol/kg) used as trapping agent was followed by sequential iv injections of sodium sulfate (2-5 mmol/kg) and sodium dichromate (0.3 mmol/kg). The mouse was placed in an L-band loop gap resonator. The observed spectra consisted of two superposed components: DMPO/SO3.- (alpha N = 14.0, alpha H = 16.0) and Cr(V) (g = 1.9798). The time course for the generation and reduction of DMPO/SO3.- was followed. The signal intensity reached a maximum at about 7 min. In vitro experiments carried out at 9.15 GHz confirmed the production of SO3.- under the conditions used for in vivo studies; the hyperfine splittings of DMPO/SO3.- produced in the in vitro experiments were the same as those produced in the in vivo studies. The production of SO.-3 is supported by oxygen uptake studies, which show that the prior addition of 300 mM DMPO inhibits oxygen consumption by SO3.-. PMID- 7786044 TI - Glucokinase of Escherichia coli: induction in response to the stress of overexpressing foreign proteins. AB - A variety of stressful conditions, such as heat shock, ethanol, osmotic shock, glucose deprivation, and oxidative stress, are known to induce the synthesis of specific proteins. Here, we report the induction in Escherichia coli of a protein elicited in response to a hitherto unidentified stress condition, i.e., the overexpression of foreign proteins. The induced protein identified as glucokinase (EC 2.7.1.2) is produced at a level > or = 20-fold higher than the level in wild type E. coli when foreign proteins are expressed under the control of the alkaline phosphatase (phoA) promoter. The bacterial glucokinase is shown to have a mass of approximately 47 kDa determined by a "renaturation activity stain assay" in situ following sodium dodecyl sulfate-poly-acrylamide gel electrophoresis and exhibits a high specificity for the phosphorylation of glucose. The apparent Km values for glucose and ATP for the enzyme are 0.15 and 0.50 mM, respectively, indicating that the E. coli enzyme is a low Km glucose hexokinase. The enzyme cross-reacts with rabbit antisera raised against hexokinase from higher eukaryotes, implicating some sequence similarity with mammalian hexokinases. Under normal conditions, E. coli glucokinase plays a minor role in glucose metabolism. However, under anabolic stress conditions, this glycolytic enzyme may be required to supplement levels of glucose 6-phosphate. Alternatively, glucokinase, which is predicted in analogy to other hexose utilizing kinases to have structural folds characteristic of hsp 70, may itself, or in combination with other E. coli proteins, function in the stabilization of newly synthesized proteins. PMID- 7786045 TI - Dental amalgam, low-dose exposure to mercury, and urinary proteins in young Swedish men. AB - Chronic exposure to inorganic mercury can cause kidney injury. Evidence gained from occupational medicine indicates that individuals who are exposed to only environmental sources, including amalgam tooth fillings, are at very little risk. Animal experiments, however, have revealed glomerular lesions of immunologic origin after low-dose exposure to inorganic mercury. In this study, the association between the number of amalgam tooth surfaces, urinary mercury, and proteinuria was explored in a sample of 48 randomly selected, apparently healthy male students who were 17-22 y of age. Presence of any of the following proteins in two separate urine samples was considered to be potentially indicative of any tubular and/or glomerular lesion: albumin, alpha-1-microglobulin (HC-protein), kappa and lambda light chains, and N-acetyl-beta-D-glucosaminidase. No significant relationship was found between any of the proteins and amalgam or urinary mercury. The results of this study did not suggest that amalgam fillings cause kidney dysfunction in humans. PMID- 7786046 TI - Symptom clusters in a community with chronic exposure to chemicals in two superfund sites. AB - Sikes and French, Ltd., two National Priority List sites that are proximal to one another, are located approximately 20 mi (32 km) east of Houston, Texas. Dumping at Sikes occurred during the early 1960s and continued until 1967. Benzene, 1,2 dichloroethane, toluene, 1,1,2-trichloroethane, naphthalene, lead, fluorene, and pyrene are chemicals that pose a particular public health concern. French, Ltd., commenced operations in 1966, and dumping ceased in 1973. Chemicals of potential public health impact at the French, Ltd., site are benzene, benzo(a)anthracene, benzo(a)pyrene, copper, chrysene, chromium, dichlorodiphenyltrichloroethane, heptachlor, lead, nickel, polychlorinated biphenyls, tetrachloroethylene, trichloroethylene, and zinc. During the 1980s, both sites were placed on the National Priority List. Barrett Station is a stable black community located near the two sites. The question of whether levels of exposure to dumpsite chemicals were related to health complaints in the Barrett Station population was examined. The prevalence of 29 symptoms reported by 321 individuals who had been highly exposed was compared with symptoms reported by a group of 351 persons from the same community who had limited exposure. A meaningful difference between the two groups emerged for some of the symptoms, the most notable of which symptoms were neurologic. Almost twice as many subjects in the high-exposure group reported five or more neurologic symptoms, compared with the low-exposure group. This excess of neurological symptoms is consistent with the known toxic properties of the chemicals at the sites. PMID- 7786047 TI - Respiratory conditions among schoolchildren and their relationship to environmental tobacco smoke and other combustion products. AB - The purpose of this study was to examine possible links between respiratory conditions among schoolchildren and exposure to environmental tobacco smoke and other home and community exposures. More than 8,000 second- and fifth-grade schoolchildren who lived in three towns along the Israeli coast were administered pulmonary function tests, and their parents completed standardized health questionnaires. The prevalence of the most reported respiratory conditions was found to be higher, some of them significantly so, among children whose fathers or mothers were smokers, compared with children of non-smoking parents. Most respiratory conditions were reported significantly more often for children who were growing up in medium- and highly polluted communities than for children from low-polluted areas. House heating with kerosene or gas was seldom associated with higher prevalence of respiratory conditions among children. No consistent r trend of reduced pulmonary function tests was associated with exposure to environmental tobacco smoke, with community pollution, or with house heating pollution. In conclusion, exposure of schoolchildren to their parents' cigarette smoke and to community air pollution is associated with higher prevalence of respiratory conditions, whereas house heating does not appear to be a public health problem in Israel. PMID- 7786048 TI - Chemical sensitivity attributed to pesticide exposure versus remodeling. AB - One hundred twelve individuals who reported onset of multiple chemical sensitivity following well-documented exposure to either (1) a cholinesterase inhibiting organophosphate or carbamate pesticide or (2) remodeling of a building completed mail-out/mail-back questionnaires concerning their exposure, symptoms, sensitivity to ingestants and inhalants, utilization of health-care resources, and impact of their illness on lifestyle. It was hypothesized that if multiple chemical sensitivity resulted from neurotoxic exposure, then organophosphate exposed respondents should report greater severity of illness resulting from the relatively greater neurotoxicity of this class of chemicals. Pesticide-exposed and remodeling-exposed multiple chemical sensitivity groups reported similar patterns of symptoms and identified similar inhalants and ingestants as triggers for their symptoms; these results suggested a common mechanism (biological and/or psychological) for their conditions. The pesticide-exposed group, however, reported significantly greater symptom severity than did the remodeling-exposed group, especially for neuromuscular, affective, airway, gastrointestinal, and cardiac symptoms. These findings provide evidence for (1) a possible biological basis for multiple chemical sensitivity and (2) a distinct pathophysiology or final common pathway for the condition that, while as yet undefined, appears to be shared by these two groups. Although subjective multisystem health complaints characterize both multiple chemical sensitivity and somatoform disorder, features of this multiple chemical sensitivity sample were inconsistent with somatoform disorder, i.e., onset after 30 y of age in 83%, the predominance of severe cognitive symptoms, and attributions of environmental causation. No group differences were found with respect to lifestyle impact. Eighty-one percent of respondents said they had been working full-time at the time they were exposed, yet at the time of the survey (on average, 7.7 y post exposure) only 12.5% were working full-time. The majority said they had quit their jobs, changed jobs, or changed careers because of their illness. Approximately 40% reported that they had consulted 10 or more medical practitioners. The persistent, disabling neuropsychological symptoms reported by these multiple chemical sensitivity groups are strikingly similar to those reported among individuals exposed occupationally to pesticides and solvents. These parallel findings suggest that the types and levels of exposures associated with extermination and remodeling may not be inconsequential, at least for a subset of the population. Further studies from a variety of perspectives, including human challenge studies and the development of animal models, are needed to define the pathophysiological and psychological mechanisms underlying this costly condition. PMID- 7786049 TI - Urinary cotinine in children and adults during and after semiexperimental exposure to environmental tobacco smoke. AB - Urinary cotinine (U-cotinine) as a biomarker of environmental tobacco smoke exposure was evaluated in 14 children (age 4-11 y) and in 7 adults who were exposed to environmental tobacco smoke at an air nicotine level of 110 mg/m3 for 2 h in a bus. Nicotine in air and U-cotinine were measured by gas chromatography/mass spectrometry before, during, and after the experiment. U cotinine rose rapidly to a maximum after a median of 6 h following the end of exposure; remained at an apparent plateau for half a day; and then decreased exponentially, with a mean half-time of 19 h (95% confidence interval 18-20 h; no significant difference between children and adults). The maximum U-cotinine was higher in the children (mean = 22 mg/l) than in the adults (13 mg/l; p = .005); decreased with age among the children (r = -.74; p = .002); and increased as the estimated inhaled nicotine dose increased. Therefore, the findings of the present study showed that young children had higher U-cotinine than adults at the same experimental environmental tobacco smoke exposure, probably because they had a higher relative nicotine dose because of a higher relative ventilation rate, and possibly also because of metabolic differences; the elimination rate did not differ. The long half-time makes U-cotinine a good biomarker of environmental tobacco smoke exposure; the time of sampling is not very critical. Dilution adjusted concentrations should be employed, and in children, preferably by density correction. A certain urinary cotinine level indicates a lower environmental tobacco smoke exposure in a small child than in an adult. PMID- 7786050 TI - Estimated long-term ambient concentrations of PM10 and development of respiratory symptoms in a nonsmoking population. AB - Site- and season-specific regressions of particulates less than 10 mu in diameter (PM10) on total suspended particulates (TSPs) were formed throughout California during years when both were monitored. The regressions were then applied to monitored TSPs for the years 1973 to 1987, and indirect estimates of PM10 were formed. These estimates of PM10 were validated by interpolating them to other monitoring stations. The split-halves correlation between the estimated and monitored mean concentrations, obtained when both were first cumulated for a 2-y period, was .86. Indirect estimates of PM10 at monitoring stations were interpolated, by month, to zip code centroids of home and work location and were cumulated for a cohort of 3,914 California Seventh-day Adventist (SDA) nonsmokers. Multivariate analyses, adjusted for several covariates, showed statistically significant (p < .05), but small, positive associations between PM10 and development of (a) definite symptoms of overall airway obstructive disease, (b) chronic productive cough, and (c) increased severity of airway obstructive disease and asthma. The relative risk (RR) associated with 1,000 h/y (42 d) exposure to concentrations of PM10 that exceeded 100 micrograms/m3 for development of airway obstructive disease was 1.17 (95% confidence interval [CI]: 1.02, 1.33); for development of productive cough, the RR was 1.21 (CI 1.02, 1.44); and for development of asthma, the RR was 1.30 (CI, 0.97, 1.73). Stronger associations were observed for those who were exposed occupationally to dusts and fumes. The RR of developing airway obstructive disease as an adult for those who had airway obstructive disease as a child was 1.66 (CI 1.15, 2.33). PMID- 7786052 TI - Air pollution and mortality in elderly people: a time-series study in Sao Paulo, Brazil. AB - The relationship between daily mortality of elderly (65+ y) persons and air pollution in the metropolitan area of Sao Paulo, Brazil, for the period May 1990 to April 1991 was evaluated by time series regression, controlling for season, weather, and other factors. Mortality was associated with respirable particles (PM10), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO). The association with PM10 was most statistically significant, robust, and independent of other air pollutants. An increase in PM10 equal to 100 micrograms/m3 was associated with an increase in overall mortality equal to approximately 13%. This association was consistent across various model specifications and estimation techniques. The dose-response relationship between mortality and respirable particulate pollution was almost linear, with no evidence of a "safe" threshold level. The results were similar to those observed in London and several U.S. cities. The results were also supportive of recent animal studies that have observed adverse health outcomes in experimental animals exposed to air pollution in Sao Paulo. PMID- 7786051 TI - Pulmonary function response to equivalent doses of ozone consequent to intermittent and continuous exercise. AB - The effects on pulmonary function of inhaling the same effective dose of ozone, as well as subjective responses during continuous exercise and intermittent exercise, were studied in 12 aerobically trained men. Each subject completed 1 h of continuous exercise at work rates that elicited a mean minute ventilation of 60 l/min, and two additional 2-h intermittent exercise exposures eliciting a mean exercise minute ventilation of 45-47 l/min (i.e., total minute ventilation for each protocol was approximately 3,600 l). Subjects were exposed in randomized sequence to 0.30 ppm ozone on three occasions and to filtered air on three occasions. Forced expiratory volume in 1 s decrements of -17.6%, -17.0%, and 17.9%, respectively, for the 1-h continuous exercise exposure and the two 2-h intermittent exercise exposures to 0.30 ppm ozone were significantly different. Exposure to ozone caused significant differences between postexposure subjective symptom responses; that is, responses associated with continuous exercise were greater than those for either intermittent exercise protocol. However, the overall symptom severity responses during the last minute of exercise for the two intermittent exercise protocols (at 90 and 105 min, respectively) were not significantly different from the continuous exercise postexposure value. The findings indicate that when the ozone effective dose is equivalent at a given ozone concentration, there is no difference between pulmonary function responses to continuous exercise or intermittent exercise exposures of 2-h duration (or less), although subjective symptoms are reduced somewhat during the last rest period of intermittent exercise. PMID- 7786054 TI - Apparent increased risk of leukemia in their highest category of exposure to tetrachloroethylene (PCE) in drinking water. AB - The potential human carcinogenicity of PCE has been the subject of study for many years, yet the largest and most recent occupational studies have not reported any increased risk of leukemia in PCE-exposed groups, let alone a risk of the magnitude suggested by Aschengrau et al. The EPA's own Science Advisory Board concluded in 1991 that PCE is a chemical "for which there is no compelling evidence of human cancer risk, accompanied by animal data of carcinogenicity whose extrapolation to humans is ambiguous." Given this background, it is not plausible that a leukemia risk of the magnitude reported by Aschengrau et al. should exist but not have been found among highly exposed occupational groups. Aschengrau et al. could contribute to our understanding of this inconsistency by presenting the additional data analysis that I have suggested. PMID- 7786053 TI - Lead in inner-city soil and its possible contribution to children's blood lead. AB - This study was designed to assess distribution and sources of lead in inner-city soils in Washington, D.C. Duplicate soil samples were collected randomly from 239 unpaved front yards of homes in Washington, D.C. Soil samples were collected 1 m from the houses. Lead concentration in soil was determined by flame atomic absorption spectrophotometry. Presence of lead detected in soil was correlated and traced to the anticipated source of origin. A significantly high concentration of lead was present in inner-city soils. Areas of the city in which the highest lead concentrations were found (Wards 1, 4, 5, 6, 7, 8) were determined to contain a large number of residents who had attained lower education levels than most residents in the remaining wards. It was concluded that lead concentration in inner-city soil plays a significant role in the incidence of lead poisoning in children in the District of Columbia and that paint is the main source of soil lead. Demographic characteristics of the residents appeared to enhance the distribution of lead poisoning. PMID- 7786055 TI - An integrated environmental asthma model. AB - Asthma is a significant public health problem in many communities. Symptoms of asthma occur as a direct or indirect result of many contributing factors, including influences from the natural and built environments, human behavior, and the adequacy of techniques used in its management. A model is presented to integrate many of these contributing factors, highlighting the characteristics of the atmosphere, i.e., climate, irritants, and allergens. The model stresses the need for investigators to heed the many contributing triggers and influences, including possible synergistic mechanisms, in this disease. PMID- 7786056 TI - Community risk perception and waste management: a comparison of three communities. AB - Three cross-sectional surveys were conducted in different regions of British Columbia, using a model of risk perception that divides the community into attitudinal and behavioral subgroups based on awareness and concern about waste management facilities. The three communities differed with respect to their levels of both awareness and concern about facilities, either planned for or situated in their region. Surprisingly, the most polarized community, which had nevertheless accepted a facility, rated this facility as more desirable than the other two communities. The unconcerned group in this community felt well informed, was more trusting of siting and operating agencies, and believed that the facility would generate benefits. The concerned group in this community also felt better informed, was more trusting of siting and operating agencies, and believed that its facility would generate benefits, compared with concerned groups in the other two communities. Longitudinal studies of the attitudes driving the siting process are needed to understand how these relationships evolve over time. PMID- 7786058 TI - Nephrology clinical outcomes. Part 1: Mortality, morbidity, adequacy of treatment, and quality of life. AB - In this presentation, Ms. Burrows-Hudson introduces objective outcome measurements for the End Stage Renal Disease (ESRD) population. Mortality, morbidity, adequacy of treatment, and quality of life are all cited as viable indicators of quality in nephrology patient care. Nephrology nurses play key roles in improving patient outcomes through ongoing interventions. PMID- 7786057 TI - The nephrology nursing practice environment: responding to changes. AB - In this session, Ms. Smith and Ms. Sims outlined the practice milieu for today's nephrology nurse. The speakers portrayed the end stage renal disease (ESRD) environment by defining the providers of care, outlining the changing characteristics of the recipients of care, and describing the effects of health care reform. PMID- 7786059 TI - Nephrology clinical outcomes. Part 2: Transplant, hemodialysis, and peritoneal dialysis. AB - Part II of the clinical outcome session dealt with treatment-specific issues as they relate to outcome. Ms. McNatt and Ms. Kleindienst described cardiovascular disease as it influences mortality and morbidity in organ transplant recipients. Ms. Hawkins outlined the impact of vascular access on patients undergoing hemodialysis treatment while Ms. Currier delineated the problem of infection in peritoneal dialysis treatment. PMID- 7786060 TI - Nurse's role in achieving patient outcomes. AB - Nephrology nursing's influence on patient outcomes has as many facets as there are practice roles in nephrology nursing. These speakers discussed the impact on patient outcomes from a variety of practice perspectives. The roles of administrator, educator, staff nurse, government nurse, research nurse, and corporate nurse are each described. PMID- 7786062 TI - A nurse entrepreneur making a difference: an interview with Patricia J. Clark.. Interview by Sally D. McCulloch, Susan T. Perras. AB - Nursing leaders have long advocated that nurses should take risks and begin operating their own enterprises in which patient care services are delivered. One such effort in the U.S. is being undertaken by ANNA member Patricia J. Clark, BSN, RN, CNN, a past president of the Keystone Chapter who is president and CEO of Nephrology Nursing Service, Inc. (NNSI) in Philadelphia. NNSI, which opened in the Fall of 1994, provides any nursing service related to the care of renal patients, including consultation to other professionals, hospitals, and dialysis facilities. In this interview, Clark details the challenges of forming a nurse operated nephrology service, her relationships and dealings with other patient care providers, and her company's long-term prospects. PMID- 7786061 TI - Consensus development conference draft documents: your opinions are important. PMID- 7786063 TI - Efforts in vein: control as a factor in one-site-itis. PMID- 7786064 TI - Chylous ascites: an unexpected complication that resembles peritonitis. PMID- 7786065 TI - Continuous renal replacement therapy in chronic hemodialysis patients. PMID- 7786066 TI - Fluvastatin: pharmakokinetic properties. PMID- 7786068 TI - Impact of nursing care on morbidity and mortality in ESRD patients. PMID- 7786067 TI - Case study of the anemic patient: epoetin alfa--focus on iron management. AB - Optimal maintenance of iron status is the keystone to sustaining normal erythrocyte production and function. Despite ongoing educational efforts for health care professionals and patients, iron management remains a challenge for clinicians managing patients who receive Epoetin alfa therapy. This article illustrates how to use a protocol to improve iron management in these patients; two case studies provide examples of the clinical application of the protocol. PMID- 7786070 TI - President's message: consensus conference helps nephrology nurses to document outcomes. PMID- 7786069 TI - Working toward consensus. PMID- 7786071 TI - Building consensus for nephrology nursing practice. AB - Building consensus for nephrology nursing practice was the theme for the American Nephrology Nurses' Association's (ANNA's) 1994 Clinical Concerns Meetings in Chicago and LaJolla, California respectively. This article emphasizes the importance of consensus building, traditional approaches to consensus conferences, and the inherent risks in conducting such a conference. Additionally, the consensus conference design and steps leading to a final working document are presented by members of the Clinical Concerns Planning Committee. PMID- 7786072 TI - Consensus for practice in the 21st century: setting a framework. AB - The American Nephrology Nurses' Association (ANNA) broke ground in specialty nursing last Fall by holding two Consensus Development Conferences in La Jolla, CA, and Chicago. In this opening presentation to conference attendees, Facilitator Anne Keane, EdD, MSN, RN, laid the groundwork to reach consensus for practice in the 21st century. Topics explored included how health care reform will influence nephrology nursing in the 21st century and what consumers and practitioners will expect and demand. PMID- 7786073 TI - 1994-1995 president's report: state of the association. PMID- 7786074 TI - 1994-1995 national directory of certified nephrology nurses. PMID- 7786075 TI - ANNA position statements. PMID- 7786076 TI - Creating an environment for positive patient outcomes: an interview with Beverly Malone. Interview by Karen E. Schardin. AB - With health care reform initiatives sweeping America, nurses must now more than ever strive to create environments to enhance positive patient outcomes. In this interview, Beverly Malone, PhD, RN, FAAN, dean of the School of Nursing at North Carolina A & T State University in Greensboro, NC, describes nurses' roles in today's managed care climate. Dr. Malone, who will deliver the keynote address at ANNA's 26th National Symposium on June 10 in Philadelphia, discusses future recruitment of students, minority issues, transforming the nursing work force, validating nursing's worth, and the future of nursing. PMID- 7786077 TI - Facilitating a "good death" in patients with end stage renal disease. AB - End stage renal disease (ESRD) patients can achieve a "good death" when planning is combined with an ethic of care. Advance directives can help to ensure that patients who want to participate in their treatment decisions may do so. An ethic of care ensures that the actual process of dying incorporates important factors such as readiness to die, appropriate interpretation of advance directives in terminal clinical situations, and proper timing of death. Nephrology nurses can play key roles in ensuring that patients die comfortably. PMID- 7786078 TI - Social support and health-related quality of life in black and white dialysis patients. AB - OBJECTIVES: To identify factors associated with health-related quality of life (HRQoL) in end stage renal disease (ESRD) patients treated with dialysis, and to identify potential racial differences in HRQoL. DESIGN: Cross-sectional study. SAMPLE/SETTINGS: 256 dialysis patients; 72 black women, 59 black men, 61 white women, and 64 white men at Piedmont Dialysis Center, a university-affiliated dialysis center in northwest North Carolina. METHODS: Information was obtained on perceived social support, social networks, blood chemistries, blood pressure, cause of renal failure, treatment-related factors, and socioeconomic factors. HRQoL indicators included two measures of life satisfaction, limitations in leisure-time activities, and Karnofsky's Physical Functioning Scale. RESULTS: On all HRQoL indicators, blacks consistently rated their HRQoL better than whites. In univariate analyses, lack of social support was consistently related to poorer HRQoL. In multivariate regression analyses, good social support and black race were the two strongest predictors of more positive responses to each of the HRQoL indicators, after controlling for the effects of the other investigated factors. With respect to the Karnofsky scale, younger age and fewer medications taken were additional significant predictors of better functioning. CONCLUSIONS: HRQoL was consistently rated better among blacks than among whites. In addition, perceived social support exerted a strong, independent influence on objectively and subjectively measured HRQoL of ESRD patients. PMID- 7786079 TI - Significance of increasing organ donations by African Americans and implications for nursing practice. AB - The scarcity of organs donated by African Americans has an important impact on the number of organs available for transplantation. An increase in the total time African Americans spend on dialysis combined with difficulty in matching human leukocyte antigens make increased organ donation by African Americans essential. Barriers to organ donation are identified and the implications for nursing practice are discussed. PMID- 7786080 TI - Peritoneal dialysis technician: a process for role definition. AB - Declining reimbursement and rising supply costs have led to use of technicians in peritoneal dialysis. This evolution has helped contain costs effectively while enhancing quality care. Recommendations for use of unlicensed assistive personnel by professional organizations include clear role definition, documented training, and delegation criteria. Applications of technician use in peritoneal dialysis allow nurses to delegate tasks to technicians in harmony with legal and professional standards. PMID- 7786081 TI - Use of sodium citrate anticoagulation in a pediatric continuous venovenous hemodialysis patient. AB - CVVHD therapy in critically ill pediatric patients presents many challenges. The ability to maintain hemodynamic stability in the face of multiple fluid and medication requirements made this therapy a successful treatment option. The difficulties often associated with heparin anticoagulation were avoided through the use of citrate, and this was achieved without any bleeding complications. Using a collaborative approach of critical care nurses from one facility and nephrology nurses from another was a unique experience. The patient benefited from the professionals' expert care. All nurses collaborated in meeting jointly set patient goals. PMID- 7786082 TI - Precautions for sports-minded patients on peritoneal dialysis. PMID- 7786084 TI - Advance practice nurses in nephrology: a response to the RPA. PMID- 7786083 TI - Case study of the anemic patient: epoetin alfa--focus on improving ventricular function. AB - Multiple factors, including chronic anemia, can impair left ventricular function and lead to serious or fatal consequences. Correcting anemia with Epoetin alfa is an important step in improving compromised left ventricular function. Continuous management of fluid status, blood pressure, and hematocrit is the best way for nephrology nurses to help patients improve their cardiac function and quality of life. PMID- 7786085 TI - Practice guidelines in cardiothoracic surgery. Ad Hoc Committee for Cardiothoracic Surgical Practice Guidelines. PMID- 7786086 TI - Inhibin functions in male rats. AB - The role of inhibin in modulating FSH secretion at sexual maturation in male rats was studied using antibodies against inhibin alpha subunit. An immunohistochemical study was performed by immunogold-silver staining; modulation of FSH secretion in sexual maturation was studied by immunoneutralization. The results show that immunoreactive inhibin alpha subunit is localized in the Sertoli cell, especially at young ages. There were no significant differences in testes weights and histology between the antibody-administered group and the control group. Marked FSH increase was observed in the antibody-administered group from 5 to 30 days. No significant difference was detected in the over 50 days group. It would appear that inhibin plays a role in suppressing FSH secretion in infantile male rats, especially before puberty. However, inhibin's role might not be particularly important, as shown by the lack of significant changes in the gonads of antibody-administered group. PMID- 7786087 TI - Correlation between sperm morphology using strict criteria in original semen and swim-up inseminate and human in vitro fertilization. AB - To study the value of sperm morphology using strict criteria in raw semen and in swim-up inseminate of human in vitro fertilization (IVF), 135 cycles of IVF with normal sperm concentration and motility were recruited. At least two mature oocytes were recovered in each cycle. The correlation between the percentages of normal forms and fertilization rates of mature oocytes was analyzed. The results demonstrate that the percentage of normal forms in both the raw semen and swim-up sample of patients with poor fertilization was significantly lower than in those with acceptable fertilization. The percentages of normal forms both in raw semen and in swim-up sample were significantly correlated with fertilization rates in vitro, however, the former seemed to have a better correlation (r = .51 and .19, respectively). Regarding the percentages of normal forms in raw semen, the fertilization rate in patients with normal forms < 4% was 6 +/- 11%, for 4-14% it was 58 +/- 36%, and for > 14% it was 88 +/- 20%. The fertilization rates were significantly different among these three groups of patients. The evaluation of sperm morphology using strict criteria in raw semen before IVF is predictive of fertilization outcome and may also help doctors to choose an optimal method of treatment for patients. PMID- 7786088 TI - Quantitative electrophoretic study of the modification of sperm plasma membrane by the ampullary gland in the golden hamster. AB - Plasma membrane proteins were extracted either from epididymal sperm after incubation with ampullary gland secretion or from uterine sperm derived from surgically treated males belonging to the following groups: TX, excision of all accessory sex glands (ASG); AGX, bilateral excision of ampullary glands; AG, excision of all ASG except ampullary glands; and SH, sham-operated. Total membrane protein, glycoprotein, and SDS-PAGE of individual polypeptide subunits were quantified. After incubation with ampullary gland secretion, both protein and glycoprotein concentrations of epididymal sperm membrane were increased. The protein profile was also significantly altered, with the removal of the 43- and 71-kD subunits and the addition of the 36- and 50-kD subunits. The in vitro results confirmed this proteolytic effect of ampullary gland and other ASG on the 43- and 71-kD subunits, despite a reduction in membrane protein concentration. Modification of the 17-, 20-, 25-, 28-, 56-, and 66-kD proteins were also observed. This report is the first demonstration that the ampullary gland is capable of modifying proteins on the sperm surface. PMID- 7786089 TI - Stimulation of ejaculated domestic cat sperm motility with caffeine, pentoxifylline, and 2'-deoxyadenosine. AB - Sperm motility patterns of cryopreserved domestic cat ejaculates treated at 37 degrees C with 1 mM caffeine, pentoxifylline, or 2'-deoxyadenosine were analyzed using computer-assisted semen analysis (CASA). The percent motility (MOT), curvilinear velocity (VLC), straight-line velocity (VSL), linearity (LIN), and amplitude of lateral head displacement (ALH) were measured for each group following 15 min of treatment. Motility indices were examined during a 6-h treatment period to determine the effect of each chemical on sperm longevity. Caffeine, pentoxifylline, and 2'-deoxyadenosine each increased (p > .05) the MOT and VCL of the ejaculates compared to the controls. The longevity of the treated and control samples were not significantly different throughout the incubation period. These results, similar to previous findings with cryopreserved epididymal cat sperm, demonstrate that motility stimulants can significantly elevate the MOT and VCL of cryopreserved ejaculated cat sperm without having deleterious effects on longevity. PMID- 7786090 TI - Effects of time and sperm concentration on reactive oxygen species formation in human semen. AB - Although generally accepted standards exist for routine semen analysis, recent methods of assessing reactive oxygen species (ROS) in human semen lack a standardized protocol. The purpose of this study was to investigate (1) the relationship between ROS level and the time interval between semen collection and analysis, and (2) the effect of sperm concentration on the level of ROS formation. Semen specimens from men (n = 40) consulting for infertility treatment were divided in two groups: in 20, routine semen analysis was performed and ROS formation evaluated at 1, 3, 5, and 24 h after semen collection; in the other 20, ROS formation was evaluated at four sperm concentrations (60, 30, 15, and 7.5 x 10(6)/mL). White blood cell (WBC) concentration was assessed before ROS measurement using a myeloperoxidase staining technique (Endtz test). ROS level was measured by a chemiluminescence method. ROS formation decreased significantly over time. The mean ROS level 343.4 (1 h), 133.5 x 10(4) cpm (3 h, p = .004), 66.0 x 10(4) cpm (5 h, p < or = .001), and 22.2 x 10(4) cpm (24 h, p < or = .001), respectively. In the first group of 20 specimens, 14 were positive for ROS formation at 1 h after collection, and 4 of these were positive for the Endtz test (> 1 x 10(6) WBC/mL). The number of ROS-positive specimens after 3, 5, and 24 h was eight, six, and two, respectively. In the second group, eight patients were positive for ROS formation at 1 h after collection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786091 TI - Effects of nicotine on sperm attachment and penetration of zona-free hamster eggs. AB - A previous study from this laboratory showed that nicotine in vitro has deleterious effects on sperm motion characteristics. This study was conducted to evaluate the effects of nicotine on the ability of human spermatozoa to attach and penetrate zona-free hamster eggs. Spermatozoa from fertile donors, washed free of seminal plasma, were incubated with medium (control) and 0.1, 1, 5, and 10 mM concentrations of nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers) for 18 h at 37 degrees C in a humid 5% carbon dioxide incubator. The sperm preparations were then mixed with enzymatically denuded hamster eggs and incubated for 3 h at 37 degrees C. The oocytes were examined by phase-contrast microscopy to enumerate the rates of sperm attachment and penetration. The data were analyzed by a paired t test and repeated measures analysis of variance using the arcsine transformation of the percentages. The percentages of eggs with attached spermatozoa significantly declined in a dose-dependent manner, the highest inhibition being at 10 mM (F = 24). The rate of sperm penetration was even more significantly decreased with the increase in nicotine concentrations in the following order: 10 mM (F = 56) > 5 mM (F = 30) > 1 mM (F = 44) > 0.1 mM (F = 12). Nicotine concentrations of 0.1 mM and above negatively affected sperm penetration of zona-free hamster eggs. PMID- 7786092 TI - Pudendal artery syndrome with erectile dysfunction: treatment by pudendal canal decompression. AB - Pudendal artery syndrome (PAS) was studied in 10 patients with erectile dysfunction (ED). Ages ranged from 38 to 55 years. All had chronic constipation and straining at stool, absent nocturnal penile tumescence, low penobrachial pressure index (p < .01), low peak flow velocity (p < .001), and a diameter increase (p < .0001) upon duplex ultrasonography screening. Four of the 10 patients had perineal hypoesthesia, prolonged bulbocavernosus reflex (p < .05), and pudendal nerve terminal motor latency (p < .05), and weak anal reflex and EMG activity of the external anal sphincter. The levator EMG activity was reduced in all patients. Intracavernous papaverine injection induced partial erection after a period longer than normal. Selective pudendal arteriography showed narrowing or obstruction of the distal part of the internal pudendal artery (IPA) on both sides with poorly or non-visualized penile arteries. A generalized arterial disease was excluded and pudendal artery compression in the pudendal canal (PC) was suspected as causing ED. The narrow or obstructed part of the IPA corresponds to the part in the PC. Four of the 10 patients had manifestations of pudendal neuropathy in addition to IPA compression. Pudendal canal decompression (PCD) was performed through a perineal approach. ED improved in 8 of the 10 patients 3-6 months postoperatively. Two of the 4 patients who had pudendal arteriopathy combined with neuropathy did not improve. In conclusion, the 10 patients with ED had common clinical and investigative findings that constitute the pudendal artery syndrome. PCD effected improvement in 80% of the cases. PMID- 7786094 TI - [Bone mineralization in Chilean children determined by dual photon bone densitometry]. AB - In 198 school age children, aged 6 to 13 years, the bone mineral density (BMD) and total bone mass (TBM) was measured in total body, lumbar spine and hip, using a double beam photon densitometer with a Gd 153 source. An increase with age of BMD and TBM was found in all the analyzed areas. At 12 years of age, TBM and BMD of total body were higher in girls than in boys. BMD of lumbar spine was significantly higher in girls than in boys at ages between 11 to 13 years. BMD of lumbar spine and femoral neck of 9 years old females were 36% and 18% respectively, lower than values of young adult Chilean females. The importance of normal values of bone mineralization for the diagnosis of bone diseases and for the evaluation of programmes directed to solve this problems is emphasized. PMID- 7786093 TI - Oxidation of polyamines in human seminal plasma: a possible role in immunological infertility. AB - Sixty-two specimens of seminal plasma obtained from normozoospermic, oligozoospermic, azoospermic, and immunologically infertile males were investigated. The levels of spermine, basal aldehyde, and aldehyde oxidation products were measured, as was the immunosuppressive activity of seminal plasma. No immunosuppressive activity was found in the immunologically infertile group; all other groups showed immunosuppressive activity. The immunologically infertile males showed low aldehyde oxidation products. PMID- 7786095 TI - [Relationship between plasmatic lipids and fat soluble vitamins in Guatemalan periurban elderly]. AB - The levels of plasmatic lipids and fat liposoluble vitamins were measured in 107 elderlies (29% males, 71% females) who were residents of a poor periurban neighborhood of Guatemala City. The age ranged between 60-103 years (means +/- sd 69 +/- 8). The mean and sd for the plasmatic levels of lipids and vitamins were (ranges in parenthesis): cholesterol 220 +/- 42 mg/dl (128 to 428); triglycerides: 189 +/- 92 mg/dl (54 to 513); retinol 50 +/- 16 ug/dl (4.5 to 103); beta-carotene 17 +/- 12 ug/dl (12 to 60), tocopherol 1.32 +/- 0.36 mg/dl (0.54 to 2.46). A significant correlation was found in both sexes between cholesterol and retinol (r = 0.3, p < 0.05) and cholesterol and tocopherol (r = 0.4, p < 0.05), triglycerides and retinol (r = 0.3, p < 0.05). Cholesterol and beta-carotene was also significant in women (r = 0.5, p < 0.05). The correlation between triglycerides and beta-carotene by gender was not significant. PMID- 7786096 TI - Accurate assessment of the quantitative significance of different sources of salt in the diet. AB - A metabolic study was conducted to assess the validity of using lithium tagged salt as a technique for monitoring the sources of salt in the diet. Discretionary sources, table and cooking salt, were separately labelled and studied, the table salt being available ad libitum whereas cooking salt intakes were controlled. The study showed that lithium excretion in the urine did provide an accurate measure of the amount of the labelled salt ingested. Subsequent analysis suggest that Li is not excreted readily in sweat or faeces so it can be used on its own to ensure the completeness of a series of 24h urines. Latin American studies on salt sources in the diet are needed as a base for programmes of primary prevention of hypertension. PMID- 7786097 TI - [Chemical and nutrition evaluation of whole sorghum flour (Sorghum bicolor, L. Moench), complementation with bean and milk whey, application in baking]. AB - The chemical characteristics nutritive value and technological properties of the whole sorghum flour for consumption were studied. The chemical analyses indicated 11.5% of protein, 2.7% of fat, 1.3% of fiber and 72% of carbohydrate. Major mineral in the flour were sulphur 0.25%, phosphorus 0.21%, potassium 0.15%, magnesium 0.07% and calcium 0.03%. The amino acid analyses showed lysine as the first limiting amino acid (score 31.3%) and as the second treonine (score 61.5%). The essential fatty acid contents in the oil were linolenic acid 36.2%, linolenic acid 1.4% and trace of arachidonic acid. The tanin content was 0.04%. PER and CEA were increased when the whole sorghum flour was supplemented with exception of digestibility. It was concluded that whole sorghum flour is a good source of calories in the diet (359 Cal/100g) and the protein responded positively to complementing with Phaseoulus vulgaris flour, dried milk whey and synthetic lysine. The bread baked with 0, 5, 10 and 15% of composite flour (wheat-sorghum) showed good volume, good external and internal characteristics and a high percentage of acceptability, by a panel of degustation testers. PMID- 7786098 TI - [Occurrence of Listeria monocytogenes in raw milk, pasteurized type C milk and minas frescal cheese commercialized in Piracicaba-Sao Paulo]. AB - Samples of raw milk, pasteurized C type milk and minas frescal cheese were analyzed for the presence of Listeria monocytogenes by a method developed for dairy products by Lovett (1) and by Lovett & Hitchins (2). A total of 20 samples of each product and from different commercial brands were analyzed, obtained from various retail stores in Piracicaba, SP. According to the pattern of sampling and methodology adopted, none of the samples of the aforesaid products was positive for the presence of L. monocytogenes or another species of the genus. It was possible to observe differences in the degree of selectivity of the selective media utilized, notwithstanding the LPM agar showing to be superior to MMA. Based on the literature and on the result obtained, becomes evident the need of a more suitable method for the detection and isolation of L. monocytogenes from foods, even when the patogen appears in low numbers, with purpose to obtain rapid, reliable and reproducible results. PMID- 7786099 TI - [Sanitary quality of some food distributed by hospital food services of Costa Rica]. AB - The sanitary quality of 100 samples of salad and 100 samples of skinless fruits distributed by the Hospital Food Services were studied. Samples were processed according to rinse solution method, and the bacteriological determination was based in the methodology described by Vanderzant & Splittstoesser. The preparation scheme of each product was realized in order to analyze risks and determine the critical control points according to ICMSF (International Commission on Microbiological Specifications for Foods). Microbiological studies on the critical control points (total and fecal coliforms determinations) were done according to the surface analysis using the swab contact method as described by Vanderzant & Splittstoesser. Our results show that 93% of the salads and 65% of the fruits presented contamination of fecal origin. The hands of the operators and kitchen utensils also presented important fecal contamination indexes. PMID- 7786100 TI - [Nutrient content in raw and processed foods derived from cereals and legumes. I: Centesimal composition and energetic value]. AB - Proximate composition and metabolizable energy of raw and processed foods derived from cereals and legumes, were determined. Results can be used to revise the out of day national composition table, to incorporate data of ash, new data of dietary fiber obtained by an enzimatic hydrolysis method, asimilable carbohydrates and metabolizable energy. They also replace the composition of various foods which were compiled from foreing tables. Difference observed on values of lipids in those foods with low lipid content, are imputed to the solvents used in the extraction. PMID- 7786102 TI - [Nutrition of children under 6 years old in Latin America. Basis for the development of food guidelines]. PMID- 7786101 TI - Physico-chemical characteristics of the Barinas nut (Caryodendron orinocense Karst. Euphorbiaceae) crude oil. AB - A proximate analysis of the seed of the C. orinocense K. (Euphorbiaceae) has demonstrated that these are a good source of edible oil. The crude oil was analyzed to determine its physical and chemical characteristics and the lipid composition, using the AOAC methods and gas liquid chromatography. The results showed that the oil meets Venezuelan standards for edible vegetable oils, with the exception of moisture content and the acid index. It is rich in polyunsaturated fatty acids (75.13% lineoleic acid), having a polyunsaturated to saturated fatty acid ratio of 6.50, and therefore could be used for human consumption. PMID- 7786103 TI - [Genetics of hypertrophic cardiomyopathies; towards molecular cardiology?]. PMID- 7786104 TI - [Demonstration of a fifth locus implicated in familial hypertrophic cardiomyopathies]. AB - Hypertrophic cardiomyopathy is familial in about 50% of cases and is transmitted in the autosomal dominant mode. The first morbid gene implicated in the disease was the gene coding the beta myosin heavy chain (beta MHC) on chromosome 14. However, only 30% of families have this genetic abnormality. Recently, three new loci have been identified on chromosomes 1q3, 11p13-q13 and 15q2. In order to determine whether other genes could be implicated in the disease a linkage analysis study was performed in a West Indian family. The method is based on the analysis of the distribution of the disease in the family and the microsatellite markers. The microsatellites used were those which recognised the 4 loci previously mentioned and 4 new markers situated and arranged with respect to known microsatellites. The results show that in the family studied, the disease did not concord with the markers of the beta MHC gene or with those recognising the loci on chromosomes 1q3, 11p13-q13 and 15q2. There is, therefore, a fifth gene implicated in familial HCM. The heterogeneity of the disease seems even greater than originally thought. PMID- 7786105 TI - [Elastic recoil after transluminal coronary angioplasty; implications of clinical and angiographic data]. AB - Secondary elastic recoil after transluminal coronary angioplasty is a constant and immediate phenomenon after successful coronary angioplasty. It was studied by quantitative coronary angiography in 75 consecutive patients undergoing transluminal coronary angioplasty. This procedure was performed on lesions presumed to be responsible for the clinical presentation. The population was divided into 3 groups: stable angina (25 patients), unstable angina (25 patients) and recent post-infarction ischaemic syndromes (25 patients). There were 57 men and 18 women (mean age 59 +/- 11 years) with 31 left anterior descending (LA), 29 right coronary (RC) and 15 left circumflex (Cx) dilatations. The lesions dilated were eccentric in 29 cases and calcified in 37 cases whereas only one thrombus was detected at coronary angiography. The elastic recoil appreciated 10 mn after the last balloon inflation was 0.97 +/- 0.28 mm for the whole population. There was no significant difference between the 3 groups studies (respectively 0.94 +/- 0.24 mm; 0.96 +/- 0.26 mm; 0.99 +/- 0.33 mm). This appeared to be greater than the RC (1.06 +/- 0.30 mm) with respect to the Cx (0.86 +/- 0.23: p < 0.02) or LAD (0.92 +/- 0.25 mm: p < 0.04). Overall, a balloon to vessel diameter ratio > 1 and a lesion length > 10 mm were parameters predicting greater secondary elastic recoil (p < 0.07 and p < 0.001 respectively), whereas the degree of eccentricity only played a role in the post-infarction ischaemic syndromes and calcification only in unstable angina (p < 0.01 and p < 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786106 TI - [Cardiac surgery in aged patients; immediate and medium-term results in 100 patients over 75 years of age]. AB - With improved operative technique and postoperative care, progressively older patients are being referred for cardiac surgery. One hundred out of 633 patients operated between September 1990 and December 1992, were over 75 years of age (Group I). These patients were compared with the last 100 patients under 75 years of age (Group II). Both groups were operated by the same surgical team with the same anaesthetic, cardiopulmonary bypass and myocardial protection techniques. The average age of the groups was 79.5 +/- 3.1 and 62.1 +/- 9.2 years, respectively. The procedures performed were: myocardial revascularisation (Group I, 28 cases; Group II, 59 cases), aortic valve surgery alone or associated with coronary bypass (56 and 22 cases respectively), and mitral valve surgery alone or associated with another procedure (11 and 12 cases). There were no significant differences between the two groups with respect to true low output state, the duration of mechanical ventilation and of intensive care and hospital stay. On the other hand, there were significant differences in: the number of blood transfusions (44 cases versus 20, p < 0.001), the occurrence of atrial fibrillation (52 cases versus 29, p < 0.001) and neuropsychiatric disturbances (27 cases versus 5, p < 0.0001). There were no cases of mediastinitis in either group. The hospital mortality was 6% in Group I and 5% in Group II (NS). The medium-term mortality after an interval of 5 to 32 months in the over 75 age group was 7 cases, including 4 cases of cerebrovascular accident. An enquiry was performed in the 87 survivors of Group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786107 TI - [Incidence and prognosis of early primary cardiogenic shock in myocardial infarction]. AB - The aim of this retrospective study was to analyse the results of coronary reperfusion on the incidence and short and medium term prognosis of early primary cardiogenic shock in acute myocardial infarction. Of 339 consecutive patients admitted within 6 hours of the onset of acute myocardial infarction, 25 (7.4%) had cardiogenic shock from the onset. The majority of patients (18) underwent direct angioplasty with a successful result in 16 cases. Intravenous thrombolysis was instituted in 5 cases followed by emergency coronary angiography leading to "rescue" coronary angioplasty in 3 cases, which was successful in 2 cases. Two patients had no coronary revascularisation because of a double contra-indication to thrombolysis and catheterization by the femoral approach. Intra-aortic balloon pumping was used in 17 cases. Complementary emergency surgical revascularization was necessary in 5 patients (20%). In all, early reperfusion of the infarct related artery was obtained in 80% of cases (20 patients). The hospital mortality was 72% (18 patients) due to refractory cardiac failure in nearly all cases. After an average follow-up of 17 months, 3 of the 7 survivors of the hospital period have died and of the 4 remaining patients, 2 are in the NYHA classes III or IV. Recent therapeutic advances have not influenced the incidence of cardiogenic shock but have significantly increased the proportion of very early cardiogenic shock, whereas the late cardiogenic shocks of more progressive onset, have nearly disappeared (4/339, 1.2% in this series). The prognosis of these early shocks, caused by severe myocardial damage, remains catastrophic and hardly improved by emergency coronary reperfusion by angioplasty and intraaortic balloon pumping.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786108 TI - [Effects of repeated and prolonged inflations on immediate angiographic results and complications of coronary angioplasty. Prospective and randomized study]. AB - The effects of the duration of balloon inflation on the immediate and mid-term results of angioplasty were assessed in a randomized study initiated in June 1992. To date, 239 lesions in 224 consecutive patients were allocated randomly into 2 groups according to the duration of balloon inflation: short duration (123 lesions): 3 or 4 successive inflations, each < or = 1 mn, for a total duration < or = 3 min; long duration (116 lesions): 3 to 5 inflations, each of 4 to 5 minutes each for a total duration > or = 12 min. Patients with acute myocardial infarction, restenosis and lesions of bypass grafts were excluded. Stenosis (% of reduction of the internal diameter) was calculated with a digitalised Philips DCI system. Success was defined by < 50% residual stenosis in the absence of severe complications: death, emergency bypass surgery, infarction and extensive and/or occlusive dissection. The baseline clinical, haemodynamic and angiographic parameters of the two groups were comparable. The residual stenosis after angioplasty in the "short duration" group was 33 +/- 11% and 29 +/- 11% in the "long duration" group (p < 0.05). The primary success rate was 75% in the "short duration" compared to 89% in the "long duration" group (< 0.001). Angiographic dissection after angioplasty was observed in 38 cases in the "short" but only in 17 cases in the "long duration" group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786109 TI - [Isoforms of creatine kinase and myoglobin in myocardial infarct treated by thrombolysis]. AB - The isoforms of creatinine kinase (CK) and myoglobin were analysed by serial samplings in 45 patients admitted consecutively for myocardial infarction treated by thrombolysis according to the usual indications. Angiographic controls were carried out systematically in the first 24 hours, including 20 cases at the end of thrombolysis. The patients were divided into two groups according to the patency of the infarct related artery: Group I (n = 35) with a patent vessel and Group II (n = 10) with an occluded vessel; 4 patients in Group II were successfully revascularised by angioplasty. The total CK had a higher peak value in Group II (2,393 +/- 1,991 UI/l at 547 +/- 247 min versus 2,888 +/- 2,189 IU/l at 584 +/- 395 min) but the difference was not statistically significant. The analysis of CK isoforms showed the MM3/MM1 ratio to be higher at the 2nd hour in Group I (3.74 +/- 2.37 versus 3.09 +/- 1.43) with a faster increase, without attaining statistical significance. A fourth CK MM fraction was observed at the 2nd hour in 71% of patients in Group I compared with only 20% of patients in Group II. Analysis of myoglobin showed a significantly earlier peak value in Group I (1,218 +/- 1,117 micrograms/l at 133 +/- 62 min versus 1,309 +/- 1,549 micrograms/l at 210 +/- 84 min). The sensitivity and specificity of these different markers were respectively 40%, 86%, 77%, and 60%, 70% and 67% for the CK (peak before 8 hours), the MM3/MM1 ratio (increase of over 35% in the first hour) and myoglobin (peak before 2 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786110 TI - [Right accessory pathways with slow and decremential anterograde conduction. Electrophysiological changes during ablation of the proximal atrial poles]. AB - Right sided accessory pathways with slow and decremential anterograde conduction differ from the anatomical substrates of the nodo-ventricular connections described by Mahaim. The connection may also be atrio-ventricular or atrio fascicular. The authors report a series of 6 patients (2 men, average age 31 +/- 9 years) with antidromic reciprocating tachycardia implicating accessory pathways with decremential conduction (wide QRS complexes with left bundle branch block) the radiofrequency ablation of which was centered on the proximal atrial pole. The increment of pre-excitation was 75 +/- 18 ms. No nodo-ventricular or nodo fascicular connections were observed. One patient had an atrio-ventricular connection, the mapping and ablation (5 applications) of which were performed on the annulus, as if it were a bundle of Kent. Five patients had a nodo-fascicular connection which was masked during sinus rhythm. The localisation of the proximal atrial insertion on the tricuspid annulus was initially estimated by studying the superior junction of the circuit and by endocavitary stimulation, and then by recording the M potential (activation of the accessory pathway). This was recorded in 4 patients, either at a specific point on the annulus (lateral or postero-lateral) which was the target of ablation (3 patients, 5 +/- 3 applications) or over a wider region (2 cm) at which ablation failed (1 patient: 13 applications). The site of the increment was determined in 2 patients and was proximal to the M potential. The M potential could not be recorded on the annulus in one patient. In 2 patients, the M potential was also recorded along the side of the pathway on the antero-lateral wall of the right ventricle of the tricuspid valve at its distal pole. In 2 patients, ablation was centered on the distal pole in second intention, near to the terminal part of the right bundle where it was localised in one of the two (18 applications). Finally, ablation was obtained in 5 out of 6 patients. They remain asymptomatic after 12 +/- 7 months follow-up. These cases show that accessory pathways with slow decremential conduction usually behave like a complete conduction pathway with an accessory laterally situated atrioventricular node on the tricuspid, an accessory bundle and a distal insertion which are all accessible to ablation. PMID- 7786111 TI - [Pulmonary arterial hypertension of chronic thromboembolic origin; therapeutic indications]. AB - Chronic thromboembolic pulmonary hypertension is a rare complication of acute pulmonary embolism. The therapeutic approach to the disease is addressed, based on a series of 81 patients referred to our department between 1984 and 1993. Medical treatment associates long-term anticoagulant therapy and, in some cases, inferior vena cava interruption. Two surgical procedures are available in selected patients: lung transplantation and pulmonary thrombo-endareterectomy. Lung transplantation has been performed in 8 patients since 1988 with 6 survivors with a maximal follow-up of 5 years. Twelve patients underwent pulmonary thromboendareterectomy with in 9 patients a dramatic functional and haemodynamic improvement. Chronic thromboembolism should be systematically investigated as the cause of pulmonary hypertension considering that in selected cases, curative surgery is possible. PMID- 7786112 TI - [The causes of intracranial hemorrhagic complications induced by antivitamins K]. AB - Cerebral haemorrhage is the main life-threatening complication of oral anticoagulant therapy. In order to identify a means of prevention, the authors undertook a retrospective study of 68 consecutive cases of anticoagulant-related intracerebral haemorrhage. The mortality was 38.5%. The respective frequency of intracerebral haemorrhage, subarachnoid haemorrhage, acute and chronic subdural haematomas was 63.2, 16.2, 10.3 and 10.3%, respectively. On admission, nearly half the patients (53%) had prothrombin ratios inferior to 25%. A predisposing factor was found in 58% of cases: hypertension (30.6%), head injury (14.5%), alcoholism or drug interaction (11.2%), and one case of intracerebral aneurysm. A history of a transient ischaemic attack or of a cerebrovascular accident was found in 10.2% of cases and 11.7% had a previous anticoagulant related extracranial haemorrhage. The initial indications for oral anticoagulation were ischaemic heart disease (32%), atrial fibrillation (20.5%), secondary prevention of venous thromboembolic disease (17.6%) and primary prevention of venous thrombosis (11.7%). The duration of treatment for isolated ischaemic heart disease was over 6 months in all cases: the average duration of treatment was 12.4 months in phlebitis and pulmonary embolism. A critical review of the indications of treatment in the light of recent recommendations showed that if inappropriate indications were rare, the sometimes unnecessary prolongation of treatment was more common. Nearly half of these cases were receiving anticoagulants when the potential benefits were questionable at the time of the haemorrhagic complication. Clinical and biological follow-up is necessary for patients on anticoagulants; minor bleeding complications may be the prelude to major haemorrhage. Biological follow-up is based on control of the international normalised ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786113 TI - [Infectious endocarditis induced by Actinobacillus actinomycetemcomitans. 8 new cases]. AB - A commensal organism of the buccal cavity, Actinobacillus actinomycetemcomitans (AAC) has been responsible for at least four new cases of infectious endocarditis by year in France. This retrospective study was based on 90 new cases of infectious endocarditis by AAC, including 8 personal observations. One third of patients had no known cardiac disease before their infectious endocarditis, the portal of entry of which was usually dental. In cases of suspected infectious endocarditis, rapid and severe weight loss (43% of cases) and, less commonly, anicteric cholestasis (8%) should alert the physician for the possible pathological role of AAC. The echocardiographic appearances are non-specific. The diagnosis is confirmed on blood cultures but the organism grows slowly in CO2 enriched atmosphere. Initially, the course of the disease was favourable in one third of patients but, in two thirds of cases, complications were observed almost renal (26%), cardiac (24%) and neurological (18%). Two thirds of patients were cured by the time they were discharged whereas the remainder had sequellae, mainly valvular and neurological. The hospital mortality was 9%; late mortality was 6%. Therefore, the prognosis of AAC endocarditis, seems to be better than that of other bacteriological forms. A combination of cephalosporin and aminoside, or even a simple third generation cephalosporin antibiotic therapy for at least 4 weeks are usually effective. The complementary surgical indications are the same as for other forms of infectious endocarditis. Prophylaxis depends on strict prophylactic amoxicillin therapy for all cardiac patients at risk of infectious endocarditis before dental treatment and on good bucco-dental hygiene. PMID- 7786114 TI - [Single coronary artery]. AB - A single coronary artery is a rare abnormality of the coronary circulation (0.09% in the authors' experience), a fortuitous finding on coronary angiography. The authors report three new cases of this abnormality, including one with a ventricular septal defect and another with ischaemic heart disease. Exercise stress testing was positive in two patients. PMID- 7786115 TI - [Spondylodiscitis disclosing endocarditis on the endocavitary electrodes of cardiac pacemakers]. AB - Permanent pacemaker electrode infection is rare but can be fatal. The authors report two cases presenting with spondylodiscitis, a previously described mode of presentation of valve endocarditis but not previously reported in this context. In one case, recurrent courses of antibiotics did not prevent repeated episodes of bacteraemia. In the second, the relapse of infection occurred at different sites of the vertebral column until surgical removal of the electrodes: the usual features of this pathology were observed: frequent but not constant infection at the site of the pacemaker implantation, making the diagnosis more difficult; delayed signs of spondylodiscitis after implantation of the pacemaker; recurrence of infection when antibiotic therapy alone was prescribed and, therefore, the need for surgical ablation of all implanted material. The authors underline the diagnostic value of transoesophageal echocardiography. PMID- 7786116 TI - [Does syndrome X exist?]. AB - The syndrome X is an entity characterised by the association of chest pain on exercise and a positive exercise stress test in patients with normal coronary angiography. However, this diagnosis can only be admitted when all other causes of angina with normal coronary arteries have been excluded. They include angina secondary to coronary artery spasm and myocardial hypertrophy. A review of the literature based on 26 publications recensing 822 patients shows that these criteria are not always respected: a really positive exercise stress test is an inclusion criterion in only 13 studies and concerns only 313 patients (38.1%); myocardial hypertrophy and coronary spasm were formally excluded in only 278 (33.3%) and 228 patients (27.7%) respectively. Taking into consideration only the patients of these 26 series with a positive exercise stress test after exclusion of coronary spasm and myocardial hypertrophy, 143 (17.4%) may be considered to be due to syndrome X. Syndrome X is a real entity but its incidence is usually overestimated. It is appropriate to distinguish it from other conditions associating, though the exercise stress test is negative, chest pain on effort and the positivity of a test considered to be indicative of myocardial ischaemia. PMID- 7786117 TI - [Angioplasty of a single coronary artery. Apropos of angioplasty of a right coronary artery arising from the left main coronary artery]. PMID- 7786118 TI - [Severe aneurysmal dilatation of the left atrium. Apropos of a case]. AB - The authors report the case of an eleven year old child with aneurysmal dilatation of the left atrial appendage and underline the diagnostic value of Doppler echocardiography in this affectation. The two signs which led to investigation of the patient and the diagnosis of this rare congenital abnormality were bulging of the left heart border on chest X-ray and atrial fibrillation. In addition to visualising a left para-cardiac chamber communicating with the left atrium on transthoracic and transoesophageal echocardiography, colour Doppler confirmed an exchange of blood between the two chambers. This aneurysm was particularly voluminous and contained echos of spontaneous contrast, a possible source of thrombosis. Thoracic CT scan and angiocardiography did not provide any further useful information. The surgical findings confirmed the presence of a large aneurysm of the left atrial appendage and excluded partial agenesis of the pericardium, the main differential diagnosis. The aneurysm was excised under cardiopulmonary bypass, and, in particular, atrial fibrillation did not recur after surgery. PMID- 7786119 TI - [Epidemiology and nosology of atrial fibrillation]. AB - Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice. It presents as chronic AF (duration > 7 days) or paroxysmal AF with intermittence of sinus rhythm giving rise to different clinical patterns which require classification. The prevalence of AF depends on the age and health of the population under consideration. The arrhythmia is exceptional in children, uncommon in young adults, but 3 to 4% of subjects over 60 years of age. Underlying cardiac disease is present in nearly 80% of cases. Valvular heart disease, though decreasing in frequency, represented 23% of cases in our hospital series. Coronary artery disease is commonly associated with AF especially in cases with left ventricular dysfunction. The relations between hypertension and AF is not clear. This relationship is more significant in the presence of left ventricular hypertrophy. Myocardial disease (hypertrophic or dilated cardiomyopathy) often underlies AF but the prognosis does not seem to be influenced by the arrhythmia. After valvular disease, cardiac failure is the most significant predictive factor of AF. Atrial fibrillation doubles the mortality and carries a 3-6% risk of systemic embolism per year, usually as a cerebrovascular accident. This risk is influenced by age, the presence of valvular disease, hypertension, previous history of myocardial infarction or cardiac failure. Idiopathic AF is a common entity (about 20% of cases in hospital series) and carries an embolic risk of 2 to 5% per year. These observations are essential for appropriate therapeutic strategy for this arrhythmia which is less benign than previously thought. PMID- 7786121 TI - [Atrial fibrillation, restoration of sinus rhythm]. AB - Conversion to sinus rhythm (cardioversion) is recommended to prevent the haemodynamic and thromboembolic complications of atrial fibrillation. Prior anticoagulation is compulsory except in emergencies. The duration of anticoagulant therapy depends on the terrain and chronicity of the arrhythmia. Cardioversion may be proposed for the majority of patients in whom it is thought that sinus rhythm can be maintained by appropriate therapy. It may be carried out pharmacologically by oral or intravenous antiarrhythmic therapy. Amiodarone is the drug of choice. Cardioversion may also be carried out by external or internal direct current shock. The success rate of external electrical defibrillation depends on the energy administered, the site of the electrodes and a number of factors related to thoracic impedence. Internal electrical defibrillation may be performed with an endocavitary catheter or by the oesophageal approach, with few complications. The main problem resides in maintaining sinus rhythm in the long term. When this is not possible, cardioversion is useless, and therapy to slow the cardiac rhythm should be instituted. PMID- 7786123 TI - [Mechanisms of atrial fibrillation: recent advances]. AB - Atrial fibrillation (AF) is due to the presence of multiple reentry pathways. Although this mechanism has been known for some time, new information has recently been acquired about the factors of atrial vulnerability and the conditions of myocardial alteration. There are two main factors of atrial vulnerability: intra-atrial conduction defects and abnormalities of the refractory periods. In addition, the concept of critical mass and the influence of the autonomic nervous system have to be taken into consideration. The abnormalities of the refractory periods liable to increase atrial vulnerability are their shortening, spatial dispersion and poor adaptation to the heart rate. All these changes may be demonstrated at cellular level. The product of the intra atrial conduction velocity and the duration of the refractory period defines the wave length. The risk of developing reentry pathways increases as the wave length shortens. Moreover, the more the atrium fibrillates, the greater will be the decrease of the refractory periods, atrial fibrillation giving rise to atrial fibrillation. Histological lesions of the atrial tissue may be demonstrated, even in the absence of underlying cardiac disease. They mainly consist of fibrosis, fatty degeneration and myocytic hypertrophy. In the long-term, atrial fibrillation leads to a number of structural abnormalities of the atrial, and sometimes ventricular tissues, progressing to cardiomyopathy in some cases. PMID- 7786120 TI - [Thromboembolic complications of arrhythmia due to atrial fibrillation]. AB - Fifteen per cent of cerebrovascular accidents have a cardiac origin, two thirds of which are due to atrial fibrillation (AF). The Framingham study showed the risk of an ischaemic cerebral event to be increased by 5.6 in AF unrelated to rheumatic heart disease and by 17.5 when AF is associated with valvular heart disease. The risk of embolism is higher in elderly subjects and in those with underlying cardiac disease. Other high risk conditions include hypertension, diabetes, hyperthyroidism and cases with echocardiographic changes: left atrial dilatation, pre-thrombotic state or intra-atrial thrombus, atheroma of the ascending aorta. This stratification of risk should be taken into account when deciding on treatment. Conscious of the importance of the risk of embolism in AF, several authors have undertaken, over the last few years, randomised studies of the prevention of thromboembolic complications of AF: the AFASAK, BAATAF, SPAF and SPINAF trials. All showed the unquestionable efficacy of warfarin, even at low doses, at the price of a haemorrhagic risk of less than 2% per year for severe haemorrhages. A more recent study (SPAF II) confirmed the value of aspirin at the dosage of 325 mg/day which would seem to be a good alternative to anticoagulant therapy when this is contraindicated, although aspirin is less effective. The indications for anticoagulant therapy have become clearer since the publication of these results. Anticoagulant therapy is essential in permanent AF whether or not associated with rheumatic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786122 TI - [Control of ventricular response in patients with atrial fibrillation]. AB - The underlying treatment of atrial fibrillation comprises two possible options. In the best of cases, sinus rhythm obtained by cardioversion must be maintained by appropriate therapy. This solution is the best option for preventing the risks of embolism or of myocardial deterioration. In refractory cases, the remaining option is to control the ventricular response. The principle is to maintain the rhythm within acceptable limits (70 to 90/min at rest), an action which also aims to limit the response to effort. This results in a symptomatic improvement and protects myocardial function. Digitalis is the commonest drug used for controlling the ventricular response. It is usually successful at recommended therapeutic doses, but often fails to control the response to effort. Adjustment of dosage using plasma concentrations may improve the situation. Another method of improving the control of the ventricular response is to associate digitalis with beta-blockers or calcium inhibitors. The risk of this option is the induction of an excessive bradycardia but, on the other hand, the response to exercise can be reduced and the variations of ventricular response decreased over a 24 hour period. In forms resistant to pharmacological treatment, it is possible to intervene directly on the atrioventricular conduction pathways. Radio frequency current is used in this indication. Sometimes, the objective is only to alter atrioventricular conduction to reduce the ventricular response to atrial fibrillation. In fact, this is often difficult to obtain and a number of cases develops complete atrioventricular block. In general, the aim is to create complete atrioventricular block which is then associated with implantation of a pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786124 TI - [Value of electrophysiological studies in the evaluation of atrial fibrillation]. AB - Electrophysiological studies of the atrium provide a means of evaluating the parameter involved in the process of fibrillation. The study of atrial vulnerability, initially limited to the test of provocation of the arrhythmia, has widened to include analysis of the substrate. Shortened refractory periods and regional conduction defects play a role in the creation of reentry pathways. Variations in the heart rate influence these parameters and explain the fundamental role of the autonomic nervous system on the uniformity of the activation front. The risk of atrial fibrillation is related essentially to thrombo-embolism: atrial vulnerability was investigated in 70 patients with unexplained cerebrovascular accidents. Globally, one out of two patients had pathological substrates. This study of atrial vulnerability showed that it was possible to identify a group of patients at risk of atrial fibrillation, even before the arrhythmia was recorded. This prognostic approach could also be applied to the investigation of preexcitation and syncope, and to the evaluation of the effects of pharmacological intervention. PMID- 7786125 TI - [Paroxysmal atrial fibrillation: role of autonomic nervous system]. AB - The electrophysiological properties of the atrial cells (duration of action potential and refractory period, conduction speed) are differently influenced by vagal and catecholamine stimulation: the first favorising phenomena of macroreentry, the second abnormal automatism and induced activity. In the normal heart, vagal tone is dominant at atrial level explaining that the clinical entity of paroxysmal vagal atrial fibrillation is observed in the absence of detectable cardiac disease in relatively young men with ECG appearances of alternating atrial flutter and fibrillation. Catecholamine-induced atrial fibrillation is usually observed with underlying cardiac disease. Besides the clinical terrain and appearances, the observation of the circumstances surrounding the triggering of atrial fibrillation and the features of the sinus rhythm and its variability before the induction of the episodes are the main factors which demonstrate the modalities of the influence of the autonomic nervous system. In cases resistant to treatment, the knowledge of these factors provides a guide to treatment, indicating which antiarrhythmic agents are poorly adapted or even harmful. PMID- 7786126 TI - [Can atrial fibrillation be managed without anti-arrhythmia drugs?]. AB - Antiarrhythmic drugs are widely used in atrial fibrillation. The demonstration of severe pro-arrhythmic effects in recent years has led to the reappraisal of their indications in this pathology. Antiarrhythmic agents have three roles: reduction of the fibrillation, maintenance of sinus rhythm and, in case of failure, control of the ventricular response. In the first indication, although intravenous injection of Class Ic antiarrhythmics is effective in 70% of cases, there is an alternative: electrical cardioversion, which is effective in 90% of cases with the transthoracic method when a certain number of technical conditions are respected. The success rate is even better with endocavitary defibrillation. Sinus rhythm is sustained in only 25% of patients at one year with placebo and in 50% of patients with antiarrhythmic therapy. The alternatives in this indication are few at present and consist in right atrial pacing in cases of vagal fibrillation and biatrial pacing for resynchronizing the activation of the two atriae when there is a major interatrial conduction defect. The control of the ventricular response, in cases of permanent atrial fibrillation, is usually reserved to digitalis, betablockers, amiodarone and some calcium antagonists. They are often inadequate and an alternative is radiofrequency catheter ablation of the atrioventricular node, which requires permanent ventricular pacing. In conclusion, there are a few alternatives to antiarrhythmic drug therapy in atrial fibrillation, but they are relatively ineffective in maintaining sinus rhythm. PMID- 7786128 TI - [Atrial defibrillator: dream or reality?]. AB - The experience acquired with the use of automatic ventricular cardiovertor defibrillator led to the idea of developing an atrial device capable of automatically detecting and reducing atrial fibrillation. The large group of patients with paroxysmal atrial fibrillation not responding to pharmacological therapy makes this a particularly relevant question. The first problem is to define the need of this type of device. There is only one group of patients with resistant and/or poorly tolerated paroxysmal atrial fibrillation in whom non pharmacological therapy is considered, for example ablation of the AV node with implantation of a pacemaker or surgery. The second problem concerns the technical feasibility of an atrial defibrillator with the difficulty related to the detection of the arrhythmia and atrial defibrillation. The recognition of atrial fibrillation may be envisaged from endocavitary signals with satisfactory specificity and sensitivity. The problems related to atrial defibrillation with low energy shocks have not yet been solved clinically, although experimental studies have given promising results. The possible dangers are dominated by a pro arrhythmic effect and the risk of ventricular fibrillation, but they could be avoided by synchronizing the atrial shock with ventricular activation based on results also obtained in the animal. Before the dream becomes reality, trials are necessary to develop a safe and effective automatic device. Intermediary stages of evaluation of such a device could include a device activated by the physician. PMID- 7786127 TI - [Surgical treatment of atrial fibrillation]. AB - The persistence of atrial fibrillation with a controlled ventricular response with medical treatment or ablation of the His bundle, suppresses troublesome palpitations but leaves potential haemodynamic problems and the risk of thromboembolism. Surgical treatment of this arrhythmia, by leaving an anatomic bridge between the sinus and atrioventricular nodes, aims to allow acceleration of the ventricular rhythm on exercise whilst preventing by partial, total or selective exclusion of atrial tissues, the multiple intra-atrial reentries responsible for atrial flutter or fibrillation. The first method proposed was isolation of the left atrium (Cox, 1980) which allows acceleration of the ventricular rhythm during exercise, leaving little or no haemodynamic disturbance, but, in theory, the same risk of embolism. The second method, the "corridor" operation (Guiraudon, 1985) consists in isolating both atria, but significantly alters the haemodynamic efficacy without reducing the embolic risk, and hardly offers any advantage over ablation of the nodo-hisian pathway completed by implantation of a ventricular, rate responsive, pacemaker. The recently described "maze" procedure (Cox and Boineau, 1991) would seem to be more promising with judiciously chosen incisions (at the base of the atria, around the pulmonary veins, between the vena cavae, along the interatrial septum, etc.) and points of cryoablation in the region of the coronary sinus, allowing modulation of the ventricular response with activation of sufficient atrial tissue to prevent reentry and recurrence of atrial fibrillation without affecting haemodynamic efficacy. The results of this technique are encouraging in the hands of its inventors but require confirmation in larger series of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786129 TI - [Atrial fibrillation]. PMID- 7786130 TI - [Current aspects of atrial fibrillation. Proceedings of conference. Paris, 17 December 1993]. PMID- 7786131 TI - [Meta-analysis of clinical trials: values and limitations]. AB - Meta-analysis produces reproductible, qualitative as well as quantitative overviews of available evidence. Such a synthesis is a compulsory step in conveying information on therapeutics to health care providers. Compared to more traditional approaches, meta-analysis has enough advantages to make them no longer relevant. Its limitations come from inappropriate use or less than required rigorous application of its methodology. PMID- 7786132 TI - [Reflections on therapeutic trials]. AB - The approach of establishing a relationship between cause and effect is a form of research contrary to the empirism which characterises many therapeutic trials. This empirism may result in certain embarrassing situations when the criteria of evaluation do not turn out to have the value that simple correlations attribute to them. Evaluating the efficacy of a drug whilst ignoring its mechanisms of action is courting danger, especially that of being unable to pursue a line of research when the global results are known in advance. These phenomena, observed in the example of the prevention of sudden death by antiarrhythmic drugs and betablockers, have the effect of impeding research in this complex field and the development of new and potentially useful drugs. It has become necessary to reevaluate the rules of medical experimentation which, in some cases, have reached the limits of feasibility and efficacy. PMID- 7786133 TI - [Should substitution criteria be used in hypertensive disease?]. AB - A number of methods, some of which are still in the development phase, enable progressively more accurate assessment of structural and/or functional changes of the target organs of hypertension. The notion that these changes may be used as a substitution criterion in the evaluation of hypertensive disease is at the heart of the concept of preclinical cardiovascular disease: in its theoretical and practical aspects, this concept stipulates that the preclinical disease is an intermediate stage between exposure to the risk factor of hypertension and the advant of morbid or mortal cardiovascular events, and it suggests that the evaluation of the preclinical disease leads to a more accurate stratification of cardiovascular risk than measurement of the risk factors alone. However, at present, none of the parameters proposed (albuminuria, left ventricular mass, arterial wall thickness) is a validated substitution criterion; but many arguments indicate that the use of these parameters as intermediate criteria is justified under certain conditions. PMID- 7786134 TI - [Coronary angioplasty: methods of evaluation]. AB - Coronary angioplasty is sometimes thought to be insufficiently validated considering the considerable development it has undergone and its place in modern cardiological practice. Nevertheless, several randomised clinical trials comparing angioplasty with medical therapy in stable angina (ACME) and with surgical treatment in stable and unstable angina (RITA) have provided more scientific support for the technique. The serious perioperative complications have become rare, the limiting factor being restenosis which is responsible for a large number of clinical recurrences and the reappearance of documented myocardial ischaemia. It is therefore logical to make restenosis the first objective of evaluation of PTCA. There are two possible approaches to this problem. The first relies on automatic quantitative operator-independent angiography as a gold standard. However, this method is methodologically complex, technically fastidious and only takes into consideration the anatomical appearances, the correlations with clinical outcome and prognosis of which are poor. It allows measurement of the amplitude of the process which is an unquestionable advantage, but it is only a partial view of the problem. The second method considers that only stenosis causing ischaemia is significant and that the criterion of evaluation should be the rate of new events and that the necessity of repeated attempts at revascularisation is the criterion of failure of the method. This overlooks the possibility of an anti-restenosis drug producing clinical results independents of its anatomical effect. Both methods have their advantages and drawbacks, which necessitates using them both in all trials of new tools or new molecules designed to prevent restenosis. PMID- 7786136 TI - [Reading of articles concerning treatment of acute phase of myocardial infarction]. AB - The number of articles concerning the treatment of acute myocardial infarction is large, and systematic analysis can improve the comprehension of their results. The object of this paper is to propose a method of classifying these articles with respect to their qualities and defects in order to orient workers towards the use of the most satisfactory articles for bibliographic purposes. The questions that have to be addressed are: what is the object of the study; is the instrument of measurement adapted to the objective of the study; which patients were studied; was the study performed with a double-blind protocol; what was the number of cases and does this number allow a valid response to the question; what was the plan of the study; what were the judgement criteria and what significance can be accorded to these criteria, and finally, what was the type of analysis, were there analyses of sub-groups, and if so, are the analyses pertinent. Based on examples in the literature, the authors justify why these questions should be asked and how the responses to these questions influence the judgement of a given article. In conclusion, the quality of therapeutic trials in acute myocardial infarction is very variable: systematic analysis allows them to be classified in a subjective scale of quality. PMID- 7786135 TI - [Nitric oxide, from vascular physiology to therapeutics]. AB - Nitric oxide (NO) synthesised by endothelial cells, plays a key role in the control of vascular tone. Its synthesis from L-arginine is assured by NO synthase, the activity of which is dependent on intracellular calcium concentrations, which are themselves modulated by pharmacological (acetylcholine, serotonin, bradykinin...) or physical factors (shearing forces exerted by blood flow). NO acts by stimulating a soluble guanylate-cyclase of the smooth muscle cells in the vessel wall. Its vasodilator effect is therefore mediated by an increase in intracellular cyclic GMP concentration. The synthesis or liberation of NO by the endothelium may be decreased or abolished during many pathological processes (hypercholesterolaemia, atherosclerosis, systemic or pulmonary hypertension...). The significance of this abnormality of NO-mediated endothelium dependent vasodilation in different pathological conditions has not been established. However, it is probably significant in view of the different properties of NO: vaso-relaxation, antiaggregant and inhibition of vascular smooth muscle growth. It is not yet known whether this abnormality is a cause or a consequence of the underlying disease. From the therapeutic point of view, NO is an active metabolite of nitrate derivatives, sodium nitroprussiate and molsidomine which therefore share the same mode of action as the so-called "endothelium-dependent" vasodilatoe agents. The inhalation of NO, which is increasingly used in neonatal and adult intensive care units, is an alternative therapeutic approach in many conditions associated with pulmonary hypertension. PMID- 7786137 TI - [Reading of the trials in cardiac insufficiency; preliminary and experimental studies (phases I-II)]. AB - In addition to general consideration concerning the justification and methodology of therapeutic trials, the interpretation of the results of evaluation of new products in the field of cardiac failure poses a number of problems. In experimental studies in the animal, the choice of model of cardiac failure, the mode of evaluation of the parameters and the justification of the choice of dosage studied require particular attention. In preliminary clinical trials (Phases I and II), the choice and number of subjects, the dosage and methodology both for recensement and interpretation of data, are factors which influence the quality of the information obtained. When these studies have been completed, the decisions whether to develop the product and the recommended dosage have to be taken. The importance of these decisions justifies the extreme attention which has to be taken in the elaboration of these studies and in their interpretation. PMID- 7786138 TI - [Reading of the trials in cardiac insufficiency; therapeutic studies (phases II B and III)]. AB - The object of therapeutic trials in cardiac failure is to improve the quality of life by controlling the principal symptoms which are dyspnoea and tiredness on effort and to improve survival. A critical review of therapeutic trials in cardiac failure must examine whether these two objectives have been attained and if they are attained simultaneously. In some cases, there is symptomatic improvement but with decreased life expectancy whereas in others, survival is prolonged without adequate control of symptoms. A critical analysis should examine the pertinence of these criteria of efficacy, and confirm that the problem of survival has been assessed, that reliable data has been provided, that the study population is representative of the real population of the patients to be treated, and finally, that the experimental protocol is realistic, i.e. a prospective study with analysis of intention to treat. PMID- 7786139 TI - [Critical analysis of scales of quality of life in cardiology; applications to cardiac insufficiency]. AB - Scales of quality of life have only recently been imposed in cardiology. Essentially an Anglosaxon invention, they have been used for evaluating most treatment of cardiac failure. The main qualities of a good quality of life questionnaire are its sensitivity, its reproducibility and its validity. The contents of the questionnaire, particularly the relationship between items concerning symptoms and those concerning the psychological aspects of the disease, have a great influence on the quality of results. The "Living with Heart Failure Questionnaire" of the University of Minnesota is the most validated questionnaire at present. As with most other methods of therapeutic assessment in cardiology, the most recently obtained results from large multicenter trials, seem to show a much smaller benefit of drugs reputed to be effective in this condition, with respect to the quality of life of patients. This justifies: the continuation of validation of these questionnaires, a reflection on the efficacy of classical management of these patients. PMID- 7786141 TI - [Hidden electric phenomena]. AB - Concealed electrical phenomena are activations which penetrate the specialised tissue incompletely, which do not have a direct electrical effect but which usually affect the conduction of the following normal impulse. The phenomena are extremely common. They arise physiologically in the node of Aschoff Tawara and express the relationship between flutter waves and their propagation to the ventricle. Any extrasystole or ectopic rhythm may give rise to these phenomena and modify conduction in the anterograde or retrograde direction if the ectopic rhythm is ventricular, by slowing the rate but also, in some cases, by paradoxically improving it. In addition, some reciprocating nodal tachycardias are due to a concealed bundle of Kent invisible in sinus rhythm, the presence of which may be suspected by the ECG appearances of the reciprocating tachycardia (negative P wave in lead 1, phenomenon of delaying bundle branch block or simply the auriculogram after the ventriculogram. PMID- 7786140 TI - [Subjectivity in the reading of scientific articles]. AB - With the examples of historical incoherencies in the diagnosis and treatment of myocardial infarction and pulmonary embolism, the author shows that it is not easy to be an objective reader of "good" scientific articles. Our neuropsychological mechanisms do not facilitate an "intelligent" attitude without the aid of affectivity. An unwanted thymotic component places the reader in an ambiguous position with respect to authority and reality. Though one can never know too much, it is difficult, alone, to maintain an intelligent curiosity. Some financial interests may awaken it. During his career, the physician has to navigate between two slightly contradictory necessities: changing his attitude with respect to new information, and according credence to his personal experience. PMID- 7786142 TI - [Ventricular fibrillation and defibrillation; electrophysiological bases and clinical applications]. AB - During sinus rhythm, the successive responses to the application of electrical stimuli of increasing intensity during the vulnerable period are cardiac stimulations followed by repetitive ventricular responses and then ventricular fibrillation. An impulse of even greater intensity is not followed by ventricular fibrillation (shock at the upper limit of vulnerability) suggesting that defibrillatory shock is effective only when it does not reinduce fibrillation. Two other hypotheses are also proposed in fibrillation, that of critical mass and that of extension of the refractory periods, in particular after biphasic shocks. Clinically, the measurement of the threshold of defibrillation is difficult as it is a random process which does not obey the all or nothing principle. Ideally, a graph of efficacy versus energy should be constructed but this is only possible under experimental conditions. The effects of different antiarrhythmic drugs have been studied in this manner; in general, the sodium channel blockers improve the energies of defibrillation. PMID- 7786144 TI - [Atrioventricular nodal tachycardia]. AB - The atrioventricular junction consists of the atrioventricular node and the bundle of His up to its division. All tachycardias arising in these structures or which depend on these structures for their sustenance are called "junctional". There are four main types. The first three correspond to reciprocating rhythms, nodal tachycardia, tachycardias using an accessory pathway with unidirectional retrograde conduction, and chronic reciprocating atrioventricular nodal tachycardia. All varieties of reciprocating atrioventricular nodal tachycardia have been well studied and their diagnosis is possible from the standard surface electrocardiogram from the position and morphology of the P' wave. They are accessible to radical treatment by radiofrequency ablation of the slow pathway or accessory pathway, when present. The definitive treatment of ectopic atrioventricular nodal tachycardia is not yet established and has to be considered case by case, this form of arrhythmia being rare. PMID- 7786143 TI - [Mechanisms of action of class III anti-arrhythmia agents]. AB - Vaughan-Williams class III antiarrhythmic agents act mainly by prolonging the duration of the cardiac action potential and, thus, the refractory period. This effect may be obtained: 1) by increasing the inward sodium or calcium currents, which may lead to an intracellular calcium overload and induce a very proarrhythmic situation, or 2) by decreasing the outward potassium currents, the objective of the new class III antiarrhythmic drugs under development. They selectively block one or several potassium channels regulated by the membrane potential (transient outward current Ito, delayed rectifying current IK and rectifying inward current IK1). Under physiological conditions the blockade of potassium channels regulated by a ligand (for example, ATP-dependent) does not lead to a class III effect. Prolongation of ventricular repolarisation is accompanied by a slowing of the heart rate and a positive inotropic effect. It is attenuated by rapid rhythms and amplified by slow rhythms: this is the reverse frequency-dependent phenomenon. However, normal frequency dependence (or "use dependence") has been reported with the ionic channel, this paradox apparently being related to the complexity of the relations between the relative contributions of the ionic currents of repolarisation and their modulation by the heart rate. The class III effect confers a proarrhythmic potential and may lead to torsades de pointes, favorised by bradycardia, hypokalaemia and hypomagnesaemia. Experimentally, it favorises early after depolarisations which are presumed to be the cellular trigger event. The comprehension of factors influencing the antiarrhythmic and proarrhythmic class III effects has led to the establishment of a pharmacological profile of the "ideal" drug conferring the least proarrhythmic risk and the best efficacy. PMID- 7786145 TI - [Hemiblocks: electrocardiographic diagnosis]. AB - Left hemiblocks or fascicular blocks are conduction defects which lead to asynchronous left ventricular activation. The classical diagnostic criteria must be respected, especially the degree of left axial deviation in complete forms. Other, less well-known criteria, which include the widening of the QRS complex opposite the myocardial walls showing delayed activation, seem very useful for making the diagnosis. The real diagnostic difficulties lie in incomplete forms because the inferior limits of axial deviation in this type of conduction defect are not known and clinical progression is usually the decisive factor. Precise understanding of the clinical signs of hemiblock is useful in clinical practice for the discussion of the significance of Q waves in the right precordial leads or for explaining sudden changes in QRS axis or amplitude. PMID- 7786146 TI - [Value of the exercise test in the study of arrhythmia]. AB - Exercise testing may be used to assess symptoms occurring on effort, to search for and evaluate arrhythmias or conduction defects, antiarrhythmic drugs, pacemakers or implantable cardioverter defibrillators. Interpretation of exercise testing is difficult because of the complexity of the factors in play. Exercise itself induces changes in myocardial metabolism and the autonomic nervous system, the nature and importance of which are influenced by the underlying cardiac disease and the presence of cardiac failure or myocardial ischaemia. This is particularly true when studying the behaviour of arrhythmias on effort, which depends on many parameters, in that they may appear or disappear during exercise, irrespective of their relationship to autonomic nervous system activation. The main problem lies in the interpretation of changes in the heart rate before the onset of an arrhythmia. The sinus rhythm is both a passive indicator of the vago sympathetic equilibrium and one of the determining factor of the arrhythmia (relationship to the rate), but it is, itself, dependent on the presence of myocardial dysfunction, a source of arrhythmias, and its changes then become difficult to interpret. These reasons explain why exercise testing is certainly a valuable tool in assessing arrhythmias but the poor reproducibility, especially in the evaluation of ventricular arrhythmias, advises prudence in the interpretation of results. PMID- 7786148 TI - Proceedings of the 1994 EUROTOX Congress. Basel, Switzerland, August 21-24, 1994. PMID- 7786149 TI - Inhibitors of the sodium pump: toxins, then drugs, and now hormones. PMID- 7786147 TI - [Electrocardiographic aspects of atrial fibrillations]. AB - The electrocardiographic analysis of atrial fibrillation is usually easy. However, some cases may be difficult to interpret: the organisation and voltage of the fibrillation waves can be very variable leading to appearances of atypical flutter in cases with large "f" waves or, conversely, in cases with low voltage fibrillation, to those of sinus mode dysfunction. The ventricular response may be slow: the conduction is usually delayed in the atrioventricular node where concealed conduction plays an important role in determining the ventricular response. Regular ventriculogrammes correspond to a junctional or ventricular escape rhythms. Aberrant conduction in the His-Purkinje system may sometimes be observed after long diastoles (phase 4 block) but often terminates short, preceded by long cycles (phase 3 block). It is usually easy to differentiate them from ventricular ectopics or preexcitation by careful examination and application of classical diagnostic criteria. PMID- 7786150 TI - Rodent responses to peroxisome proliferators--a receptor-mediated phenomenon? PMID- 7786151 TI - Role of second messengers in mineral particle-induced production of reactive oxygen species by phagocytes. PMID- 7786152 TI - Estrogenic effects of some xenobiotics. PMID- 7786153 TI - In vitro methods in regulatory toxicology: the crucial significance of validation. PMID- 7786154 TI - Scientific, ethical and legal aspects of the acceptance of in vitro methods in regulatory toxicology. PMID- 7786155 TI - The validation and use of in vitro teratogenicity tests. PMID- 7786156 TI - In vitro methods in regulatory toxicology. PMID- 7786157 TI - In vitro tests in regulatory toxicology: symposium chairman's summing-up. PMID- 7786158 TI - Ex vivo and in vitro models in acetaminophen hepatotoxicity studies. Relationship between glutathione depletion, oxidative stress and disturbances in calcium homeostasis and energy metabolism. PMID- 7786160 TI - Neurobehavioral abnormalities induced by prenatal exposure to substances of abuse -stating the problems. PMID- 7786159 TI - Rabbit renal proximal tubule suspensions as a model for nephrotoxicity evaluation of native or in situ metabolized beta-lactam antibiotics. PMID- 7786161 TI - Applications for transgenic animals in toxicology. PMID- 7786163 TI - Delayed developmental neuro- and immunotoxicity of benzodiazepines. PMID- 7786162 TI - Prenatal exposure to marihuana and tobacco during infancy, early and middle childhood: effects and an attempt at synthesis. AB - Both marihuana and cigarettes appear implicated, in a differential fashion, in the neurobehaviour of infants and children born to women who used these substances during pregnancy. In a low-risk upper middle class sample, marihuana use was associated, in the newborn, with mild withdrawal symptoms and some autonomic disruption of nervous system state regulation. However, between 6 months and 3 years of age no behavioural consequences of marihuana exposure (once confounding factors were controlled) were noted. At four years of age, although global tests of intelligence did not differentiate exposed from non-marihuana exposed children, verbal ability and memory were associated with in utero marihuana exposure. At five and six years of age these general areas were also noted to be associated with maternal cannabis use as was sustained attention. These areas of neurobehavior that appear affected by marihuana exposure during fetal development are ones that are consistent with the cognitive construct of 'executive functioning' which is thought to be a marker of prefrontal lobe functioning. Consistent with the observations derived from these children is that prefrontal functioning may not be apparent until approximately four years of age and that executive functioning is disassociated from measures of global intelligence. Exposure to cigarettes during pregnancy appears to be associated with neurobehavioural deficits in the auditory domain. In the newborn this is manifested by decreased responsivity to sound and altered auditory habituation. Between the ages of one and 11 years the performance on auditory related tasks (verbal memory, language, auditory processing) were consistently the domains that differentiated the cigarette exposed from the non exposed children. The possible role of the cholinergic mediated efferent auditory system is discussed. Also associated with in utero exposure to cigarettes were general cognitive performance and parental reports and objectively derived measures of impulsivity. The striking degree of consistency over the years lends strength to the interpretation that the observations in childhood have, at least as their partial etiology, the prenatal exposure to cigarettes. However, in interpreting the evidence presented it must be recognized that the alterations in the child's behaviour may well affect the parenting behaviour. This potential transactional interaction must remain an integral part of drawing conclusions about both marihuana and cigarette's effects. PMID- 7786164 TI - Changes in EEG of freely-moving rats caused by three-generation organophosphate treatment. PMID- 7786165 TI - Developmental neurotoxicity of carbon monoxide. AB - The results of recent studies dealing with behavioral and electrophysiological dysfunctions induced in rat offspring by prenatal exposure to relatively mild CO concentrations (75 and 150 ppm) have been reviewed in the present paper. In particular, gestational exposure to CO produced the following behavioral changes: (i) reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest; (ii) decrease in ultrasonic responsiveness to a challenge dose of diazepam; (iii) alterations in the acquisition of an active avoidance task. The electrophysiological changes induced by prenatal CO in peripheral nervous system are as follows: (i) increase in time constants of sodium current inactivation; (ii) increase in the percentage of the maximum number of activatable sodium channels at the normal resting potential; (iii) negative shift of sodium current reversal potential. Moreover, results of ongoing researches on peripheral myelinogenesis in rats exposed to CO during gestation will be also summarized. PMID- 7786166 TI - Concepts, potentials and methods for constructing transgenic cells and animals. PMID- 7786167 TI - The safety assessment of over-the-counter (OTC) products. AB - In recent years many compounds have become available as Over-The-Counter (OTC) medicine, for self-medication, which were originally marketed as prescription medicines only. This has been coupled with changes in the consumers' behaviour to self treatment and the governments commitment to restrict rising health costs. The safety and safe use of OTC products are important considerations for their wide distribution which is paralleled by diminishing medical supervision. OTC products were generally registered when toxicological requirements differed from the stringent guidelines of today, and their safety assessment thus often involves ongoing evaluation as new data become available. For this, human data must also be integrated for these assessments. However, in some areas, such as mutagenicity and carcinogenicity testing, human data are hardly obtainable and testing in animals or cells, is ultimately the only reliable source for extrapolation to man. Routine toxicological methods have mainly been developed for the assessment of new pharmaceutical entities and often provide 'yes/no' answers only. Data of such tests are, therefore, not directly applicable to the safety assessment of OTC products. Additional information on the kinetics in animal and man are indispensable for such extrapolation. On the other hand, modifications of original test protocols for the assessment of new formulations are indispensable. It was the aim of this workshop to discuss general approaches of safety assessments within the important new area of OTC products, as well as to present specific cases of recently arisen safety issues. PMID- 7786168 TI - OTC pharmaceuticals and genotoxicity testing: the paracetamol, anthraquinone, and griseofulvin cases. AB - Genotoxic effects are hardly assessable in an exposed population but are generally considered to be serious due to their unpredictable effects on subsequent generations and to the link between genotoxicity and cancer. Lack of knowledge about a genotoxic/carcinogenic potential has to be stated for numerous compounds which are often in pharmaceutical use known for a long time. A thorough testing programme like it is done for new compounds is essential for such compounds that are not completely unsuspicious with respect to being reactive with macromolecules or that have the potential to generate reactive metabolites in the body. Paracetamol, anthraquinone-containing preparations, and griseofulvin are examples for pharmaceuticals that have been in use for a long time but for which genotoxicity testing revealed a possible deleterious potential only recently. The Federal Health Office/Federal Institute for Drugs and Medical Devices therefore imposed new studies upon companies marketing these compounds in the last years. These studies in part led to a more thorough description of possible adverse effects or even restrictions for use. Paracetamol exhibits a genotoxic potential in vitro and in vivo probably via indirect, cytotoxicity or enzyme inhibition-mediated effects. Further studies will have to clarify whether a threshold could be established and whether effects do not occur at therapeutic dose levels. Genotoxicity data on the mixed group of anthraquinones reveal positive and negative findings. Compounds such as lucidin, danthron, emodin supposedly have a genotoxic and carcinogenic potential. Further studies with anthraquinone-containing plant preparations will have to clarify the content and genotoxic activity of the preparations and the active ingredients. Lucidin- and danthron-containing preparations are currently no longer in use now whereas restrictions apply for other anthraquinone-containing laxatives. Griseofulvin is acknowledged in the meantime as an aneugen for somatic and germ cells. It is in vitro effective in concentrations that correspond to therapeutic plasma levels. PMID- 7786170 TI - Safety assessment of OTC products--a regulatory view. PMID- 7786169 TI - Safety assessment of OTC drugs: doxylamine succinate. PMID- 7786172 TI - Species specificity of organ toxicity. PMID- 7786171 TI - Drug toxicity findings and no action taken. PMID- 7786173 TI - Mechanisms underlying species-specificity in target organ toxicity. PMID- 7786174 TI - Principles, benefits and limitations of the NOEL approach. PMID- 7786176 TI - Development of OECD Test Guidelines and Hazard Assessment procedures for terrestrial effects [Organization for Economic Co-operation and Development]. PMID- 7786175 TI - Species specificity of organ toxicity: behavioral differences. PMID- 7786177 TI - Development of guidance for terrestrial effects assessment. [Organisation for Economic Co-operation and Development]. PMID- 7786178 TI - Application of quick and simple plant bioassays to assess the genotoxicity of environmental pollutants--detection of potential health hazards of air, water and soil contaminants. PMID- 7786179 TI - Comparison of susceptibilities of species used in toxicological and environmental risk assessment to chemicals (pesticides). PMID- 7786180 TI - Comparison of BMD with NOAEL and LOAEL values derived from subchronic toxicity studies. PMID- 7786181 TI - Toxicological evaluation of pollutants in soil--concept of the AGU* and assessment of tolerable concentrations for metals. PMID- 7786182 TI - The SCID (severe combined immunodeficiency) mouse--its biology and use in immunotoxicological research. PMID- 7786183 TI - The SCID mouse as a tool to bridge the gap between animal and human responses. PMID- 7786184 TI - The SCID mouse and its use for immunopharmacological and immunotoxicological investigations. PMID- 7786185 TI - Chirality--from molecules to organisms. PMID- 7786186 TI - Interactions between the in vitro metabolism of xenobiotics and fatty acids. The case of ibuprofen and other chiral profens. PMID- 7786187 TI - Side effects and toxic reactions of chiral drugs: a clinical perspective. PMID- 7786189 TI - Biological behavior of prestages of cancer cells: an introduction. PMID- 7786188 TI - Analysis of (S)- and (R)-propranolol in human plasma and urine by a specific immunoenzymatic assay versus HPLC. PMID- 7786190 TI - Preneoplastic lesions in kidney and carcinogenesis by non-genotoxic compounds. PMID- 7786192 TI - The UK approach to the regulation and evaluation of novel foods produced by biotechnology. PMID- 7786191 TI - Early cellular alterations in chemical liver carcinogenesis as addressed by immunohistochemical and molecular biological techniques. PMID- 7786193 TI - Biomarkers in ecotoxicology: an overview. PMID- 7786194 TI - Use of recombinant cells in metabolic and mechanistic studies. PMID- 7786195 TI - Use of cytochrome P450 1A (CYP1A) in fish as a biomarker of aquatic pollution. PMID- 7786196 TI - Cellular and molecular biology of aryl hydrocarbon (Ah) receptor-mediated gene expression. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds elicit diverse toxic and biochemical responses in laboratory animals and mammalian cells in culture. TCDD induces CYP1A1 gene expression and results of extensive research have delineated the molecular mechanism of this response. In target cells, TCDD initially binds to the aryl hydrocarbon (Ah) receptor which accumulates in the nucleus as an Ah-receptor:aryl hydrocarbon nuclear translocator (Arnt) protein heterodimeric complex. The nuclear Ah receptor complex acts as a ligand-induced transcription factor which binds to transacting genomic dioxin/xenobiotic responsive elements (DREs/XREs) located in the 5'-regulatory region upstream from the initiation start site and this interaction results in transactivation of gene transcription. DREs have been identified in several other genes which are induced by TCDD, including CYP1A2, aldehyde-3-dehydrogenase, NAD(P)H quinone oxidoreductase, and glutathione S transferase Ya and similar induction response pathways have been observed or proposed. However, TCDD and other Ah receptor agonists also inhibit expression of several genes and research in this laboratory has investigated inhibition of estrogen (E2)-induced genes including uterine epidermal growth factor, c-fos protooncogene, and the progesterone receptor, estrogen receptor (ER) and cathepsin D genes in human breast cancer cell lines. In MCF-7 human breast cancer cells, E2 induces cathepsin D gene expression and this is associated with formation of an ER/Sp1 complex at the sequence in the promoter region (-199/-165) of this gene. Within 30 min TCDD causes a rapid inhibition of E2-induced cathepsin D gene expression in MCF-7 cells. Moreover, using a series of synthetic oligonucleotides which include the wild-type ER/Sp1 and various mutants, it was shown by gel electromobility shift and transient transfection assays that the nuclear Ah receptor complex binds to an imperfect DRE located between the ER and Sp1 binding sequences. This interaction results in disruption of the ER/Sp1 complex and inhibition of E2-induced gene expression. These results illustrate that the nuclear Ah receptor complex also exhibits activity as a negative transcription factor via a mechanism which is similar to that reported for Ah receptor-mediated induction of gene expression. PMID- 7786197 TI - The corneal endothelium and myopic excimer laser photorefractive keratectomy. PMID- 7786198 TI - Is a 'favorable' outcome acceptable? PMID- 7786199 TI - Oral imipramine and acute angle-closure glaucoma. PMID- 7786200 TI - Acute uveitis in patients with acquired immunodeficiency syndrome receiving prophylactic rifabutin. PMID- 7786201 TI - Choroidal hyperpermeability in central serous choroidopathy: a new concept? PMID- 7786202 TI - Transconjunctival entropion surgery. PMID- 7786203 TI - The Wisconsin Epidemiologic Study of Diabetic Retinopathy. PMID- 7786204 TI - Partial splitting of the anterior lens capsule giving a 'double-ring' sign. PMID- 7786205 TI - Management of ablation decentration following excimer photorefractive keratectomy. PMID- 7786207 TI - Ischemic optic neuropathy during corticosteroid therapy for giant cell arteritis. PMID- 7786206 TI - Rifabutin-associated uveitis during prophylaxis for Mycobacterium avium complex infection. PMID- 7786208 TI - Questions concerning the role of apraclonidine in the management of glaucoma. PMID- 7786209 TI - The effectiveness initiative. I. Medical practice guidelines. AB - We examined the impact of the "effectiveness initiative" and medical practice guidelines on the practice of ophthalmology. The effectiveness initiative asserts that much of current medical practice is unnecessary or harmful, too costly, and unresponsive to patient desires. It promotes more critical review of the medical literature, research on outcomes, and stringent practice guidelines. Whereas current practice guidelines are helpful in codifying accepted procedures, they tend to sanction interventions of unproved value. Future guidelines will probably reject unproved interventions, especially if they are expensive. Although such guidelines may limit physicians' freedom of choice, they may protect them against capricious malpractice claims and unreasonable patient expectations. PMID- 7786211 TI - Teaching ophthalmology to primary care physicians. The Association of University Professors of Ophthalmology Education Committee. AB - The evolution of our health care system toward managed care has placed primary care "gatekeeper" physicians in a position where they must examine and treat patients with diseases that are ordinarily treated by medical and surgical subspecialists. Many of these physicians may be poorly prepared to accept this new responsibility. The Association of University Professors of Ophthalmology (AUPO) has published a Policy Statement on Medical Student Education that suggests the minimum level of competence expected of general physicians when dealing with ophthalmologic problems. A recent survey of directors of residency programs in family practice, internal medicine, and pediatrics revealed that the training of primary care physicians (as opposed to academicians or subspecialists) has become a nearly universal programmatic goal. Most program directs believe that less than half of their residents meet the AUPO standard at the completion of medical school, and a significant minority do not meet the AUPO standard at the completion of their residency. An overwhelming majority of program directors believe that additional training in ophthalmology and other subspecialties should be incorporated into the training programs of primary care physicians. Ophthalmologists and other subspecialists should develop programs at the medical student level directed toward the education of primary care physicians, and should participate in the training of primary care physicians, as well as their own subspecialty residents. In the future, the primary care physician must be considered part of the "eye care team." Enhancing the ophthalmologic education of primary care physicians is in the best interest of quality patient care. PMID- 7786212 TI - A comparison of topical diclofenac with prednisolone for postcataract inflammation. AB - OBJECTIVE: To compare diclofenac sodium with prednisolone acetate for the control of postoperative inflammation after cataract surgery. DESIGN: Fifty-two patients undergoing phacoemulsification with posterior chamber intraocular lens implantation were randomly assigned to receive either 0.1% diclofenac eye drops or 1% prednisolone eye drops as their postoperative anti-inflammatory medication. The patients were examined 1 day (baseline), 1 week, and 1 month after surgery. Postoperative inflammation was evaluated subjectively by slit-lamp assessment of cell and flare and objectively by measurement of cell and flare with a laser cell and flare meter. RESULTS: At each visit, there was no statistically significant difference in postoperative inflammation either by slit-lamp assessment or with the laser cell and flare meter for the two treatment groups. CONCLUSION: In the dosage used, diclofenac was as effective an anti-inflammatory agent for uncomplicated post-cataract inflammation as prednisolone. PMID- 7786213 TI - Features of age-related macular degeneration in a black population. The Barbados Eye Study Group. AB - OBJECTIVE: To report on the frequency of features of age-related macular degeneration in a black population based on fundus photograph gradings. DESIGN: Population-based study. SETTING: Barbados, West Indies. STUDY POPULATION: Residents of Barbados, selected by a random sample of Barbados-born citizens, aged 40 to 84 years. MAIN OUTCOME MEASURE: Gradings from 30 degrees stereoscopic macular photographs. RESULTS: Black participants (n = 3444) completed examinations at the study site and had gradable macular photographs in both eyes. Drusen larger than 63 microns occurred with comparable frequency in men and women. The frequency of small drusen decreased with age, while medium and large drusen were more common in older participants. Frequencies of all age-related macular degeneration-related characteristics were similar for men and women except for small drusen, which occurred more commonly in women. Confluent drusen and pigment atrophy also increased significantly with age. Exudative features occurred in 0.5% of the participants. CONCLUSIONS: This study provides population based data on the frequency of features of age-related macular degeneration based on photographic gradings of a black population. Features of early age-related macular degeneration were common, but appeared at a lower frequency than has been reported for white populations. Exudative disease was infrequent, occurring in about one of 200 participants. PMID- 7786210 TI - Socioeconomics viewpoint: the need for an update of the clinical practice guideline on cataract. AB - In June 1994, the Agency for Health Care Policy and Research (AHCPR), Washington, DC, called a meeting to hear opinions on the need for a reconstituted panel to revise the recently published clinical practice guideline Cataract in Adults: Management of Functional Impairment. The need and timing of a revision depend essentially on the answer to two questions: (1) Are there serious flaws in the previous panel's work that would necessitate a re-review? or (2) Is there new scientific information that can be critically assessed that would substantially alter the recommendations of the guideline? It is important to consider these questions with care because any revision is likely to be both costly and time consuming. PMID- 7786214 TI - Sudden visual loss associated with sexual activity. AB - OBJECTIVE: To characterize the ocular fundus findings of patients who suffered sudden visual loss associated with sexual activity. DESIGN: Case series. SETTING: Outpatient ophthalmic practice. PATIENTS: Six patients presented with a precipitous decrease in vision in one eye with no apparent predisposing factors. After obtaining a careful history, each patient revealed that he or she had been engaging in rigorous sexual activity immediately before experiencing the visual loss. INTERVENTION: Five of the six patients were followed up without intervention. One patient required prophylactic laser photocoagulation of a retinal tear to decrease the risk of retinal detachment. RESULTS: Six patients aged 24 to 53 years suffered sudden loss of vision secondary to intraretinal, preretinal, or vitreous hemorrhaging. Visual acuity in the affected eyes ranged from a mild decrease (20/40) to profound visual loss (counting fingers at 6 in). Five of the six patients were followed up for at least 1 month and showed spontaneous improvement in vision as the blood cleared. Those who returned for long-term follow-up enjoyed complete visual recovery without any sequelae. CONCLUSIONS: Sudden debilitating visual loss may occur during sexual activity from the rupture of retinal blood vessels in the macular region or from the development of vitreous bleeding from an induced retinal tear. The long-term prognosis after such hemorrhaging appears to be excellent, with good visual recovery occurring as the blood resorbs spontaneously. PMID- 7786215 TI - Dietary fat and age-related maculopathy. AB - OBJECTIVE: To describe the relationship between type and level of fat in the diet and the prevalence of age-related maculopathy. DESIGN: Retrospective population based study. SETTING AND PARTICIPANTS: Residents of Beaver Dam, Wis, between the ages of 45 and 84 years, participating in the Beaver Dam Eye Study and Nutritional Factors in Eye Disease Study. DATA COLLECTION: Presence and severity of age-related maculopathy were determined from masked grading of fundus photographs taken from 1988 through 1990. Diets in the past (1978 through 1980) were assessed retrospectively using a food frequency questionnaire during in person home interviews. RESULTS: Persons with intake of saturated fat and cholesterol in the highest compared with the lowest quintile had 80% and 60% increased odds for early age-related maculopathy, respectively, after adjusting for age and intake of beer. These relationships were not influenced by adjusting for several other potential confounding variables (carotenoid intake, intake of vitamins C or E in supplements, smoking, body mass index, time spent outdoors in the summer, gender, and history of diabetes, hypertension, or cardiovascular disease). Odds ratios for late age-related maculopathy were in similar directions but were not statistically significant. CONCLUSIONS: High intake of saturated fat and cholesterol is associated with increased risk for early age-related maculopathy in the Beaver Dam population. This supports the hypothesis that atherosclerosis or its risk factors are related to age-related maculopathy. Confirmation of this finding in other populations and in prospective studies is needed. PMID- 7786217 TI - Outcome of corneal grafting with donor tissue from eyes with primary choroidal melanomas. A retrospective cohort comparison. AB - OBJECTIVES: To determine if melanomas have occurred in the recipients of corneas from donor eyes with primary choroidal melanomas and to determine the success of corneal grafting with tissue taken from eyes with primary choroidal melanomas. DESIGN: Retrospective cohort comparison and follow-up patient questionnaire. SETTING: A tertiary medical center in Rochester, Minn. PATIENTS: In patients who received corneal transplants, we reviewed 47 consecutive corneas transplanted from donor eyes enucleated for choroidal melanomas and compared them with 47 corneal grafts from donor eyes without melanomas matched for recipient age (+/- 10 years), date of operation (+/- 12 months), corneal storage time (+/- 24 hours), and operation type. RESULTS: No melanomas occurred in either group over a mean follow-up of 5.4 years (range, 0.4 to 15 years). There was no significant difference between the two groups in corneal thickness and endothelial cell loss at 2 months and 1 year after transplantation and in the probability of a rejection episode. CONCLUSIONS: There is no evidence of tumor transmission by transplantation of corneas from donor eyes with primary choroidal melanomas. Corneas transplanted from donor eyes with primary choroidal melanomas have similar outcomes to corneas transplanted from donor eyes without melanomas. PMID- 7786218 TI - Keratoprosthesis with biocolonizable microporous fluorocarbon haptic. Preliminary results in a 24-patient study. AB - BACKGROUND: Most complications of a keratoprosthesis occur at the tissue-to implant interface. The ideal prosthesis would eliminate this interface by having the tissue actually grow into the supporting material. We present a prospective clinical human study of a novel biocolonizable keratoprosthesis in 24 eyes of 24 patients. DESIGN: To promote implant stability, the 9-mm-diameter haptic was fashioned using a custom-made microporous fluorocarbon with a 4-mm-diameter, 2.67 mm-long, central optic made of medical grade polymethylmethacrylate, giving a global visual field of 110 degrees to 130 degrees. Only bilaterally blind patients with untreatable corneal diseases were included in the study. The haptic was inserted into a lamellar pocket delaminated in the stroma, and the optic was positioned through a hole trephined in the central cornea. RESULTS: The average follow-up was 15.7 months (range, 4 to 28 months). The host corneal fibroblasts penetrated and proliferated into the peripheral microporous fluorocarbon and provided anchorage between the cornea and prosthesis. Seventeen patients (70.8%) had visual acuity improvements. Mean corrected final visual acuity was 20/100 (range, 20/30 to 20/400). Five anatomic failures occurred in the first 6 months (three extrusions, one dislocation of the optic, and one endophthalmitis). We had one case (4.1%) of treatable glaucoma. We successfully removed four of five retroprosthetic membranes that had occurred. No retinal detachment occurred. CONCLUSION: The biocompatible inert microporous polymer did not eliminate all mechanical complications associated with a keratoprosthesis. PMID- 7786216 TI - The National Basketball Association eye injury study. AB - OBJECTIVE: To investigate the epidemiology of eye injuries sustained by professional basketball players in the National Basketball Association (NBA). METHODS: A prospective study involving all NBA athletes who sustained eye injuries between February 1, 1992, and June 20, 1993, was conducted. Twenty-seven NBA team athletic trainers, physicians, and ophthalmologists were provided data forms to complete for any player examined for an eye injury. Practice and game exposures during the preseason, regular season, playoffs, and championships were included. RESULTS: Of the 1092 injuries sustained by NBA players during the 17 month period, 59 (5.4%) involved the eye and adnexa. Eighteen (30.5%) of the injuries occurred while the player was in the act of rebounding, and 16 (27.1%) while the player was on offense. The most common diagnoses included 30 abrasions or lacerations to the eyelid (50.9%), 17 contusions (edema and/or ecchymosis) to the eyelid or periorbital region (28.8%), and seven corneal abrasions (11.9%). There were three orbital fractures (5.1%). Most injuries were caused by fingers (35.6%) or elbows (28.8%). Nine players (15.3%) missed subsequent games because of their injury. Fifty-seven players (96.6%) were not wearing protective eyewear at the time of injury. CONCLUSIONS: The incidence of eye injuries in NBA players during the 17-month period was 1.44 per 1000 game exposures. Frequent physical contact in professional basketball players leaves them at great risk for sustaining eye injuries. To prevent these injuries, protective eyewear is recommended. PMID- 7786219 TI - The incidence of corneal abnormalities in the Silicone Study. Silicone Study Report 7. AB - OBJECTIVE: To determine factors that were prognostic of corneal abnormalities in eyes following surgery for severe proliferative vitreoretinopathy. DESIGN: Subgroup analysis of the Silicone Study. SETTINGS: Community and university-based ophthalmology clinics. MATERIALS: Eyes with attached maculae at the 24-month follow-up examination that did not have a pre-existing corneal abnormality. INTERVENTIONS: Vitrectomy surgery with long-acting gas or silicone oil. OUTCOME MEASURES: Epithelial and/or stromal edema, corneal opacity and/or previous corneal transplant. RESULTS: The incidence of corneal abnormalities at 24 months was 27% and did not differ significantly between treatment groups. Prognostic factors were preoperative aphakia or pseudophakia (P = .003), preoperative iris neovascularization (P = .006), reoperation (P = .001), the absence of a fluid/gas exchange (P = .03), corneal touch by silicone oil (P = .02), and the presence of aqueous cells (P = .009) or aqueous flare (P = .08). In a multivariate analysis, independent prognostic factors were iris neovascularization (relative risk [RR] = 13.1), aphakia or pseudophakia (RR = 3.0), postoperative aqueous flare (RR = 5.4), and reoperations (RR = 3.4). Corneal abnormalities were correlated with poor visual acuity and hypotony (P < .001). CONCLUSIONS: To our knowledge, this is the first study to document that the incidence rates of corneal abnormalities are equivalent between oil and gas. The incidence of corneal abnormalities in gas filled eyes was higher than expected, and remained high in oil-filled eyes, despite the use of an inferior iridectomy. Successful surgical repair of the retinal detachment with a single operation, and prevention and early management of corneal touch by silicone oil should help to prevent corneal abnormalities. If rubeosis iridis or severe aqueous flare is present, preoperative treatment with intense topical and possibly periocular steroids might reduce inflammation, which might mediate corneal damage. PMID- 7786221 TI - Epithelial inclusion cyst of the iris. AB - We describe the clinical presentation, high-frequency ultrasound biomicroscopic characteristics, and pathologic findings associated with a conjunctival inclusion cyst within the iris. The patient had undergone an uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens insertion 9 months prior to presenting with a progressively enlarging iris mass. A clinical examination revealed a solid-appearing white tumor within the midiris stroma, accompanied by limbal-conjunctival hyperemia and anterior chamber inflammation. Ultrasound biomicroscopy revealed an egg-shaped solid iris stromal tumor that displaced the pigment epithelium. The mass was composed of three concentric layers of different echogenicity: a moderately reflective mantle, a less reflective middle zone, and a hyperreflective core. Within 3 days of initiation of topical corticosteroid therapy (prednisolone acetate, 0.5 mg per drop four times daily), the tumor enlarged and induced a plasmoid aqueous and a hypopyon. Histopathologic study revealed a conjunctival inclusion cyst with evidence of acute and chronic inflammation. We have found that the diagnosis of epithelial inclusion cyst within the iris can be aided by an ultrasound evaluation. This case also suggests that it may be preferable to excise these tumors prior to topical corticosteroid treatment. PMID- 7786220 TI - Prevalence of foveal lesions in type 1 and type 2 Usher's syndrome. AB - PURPOSE: To evaluate possible differences in the prevalence of clinically detectable foveal lesions between patients with type 1 and type 2 Usher's syndrome. METHODS: Records of 48 patients with type 1 and 98 patients with type 2 Usher's syndrome were retrospectively evaluated for the presence of a foveal lesion. The age, gender, and racial distribution of patients were similar in the two subtypes. Two investigators reviewed fundus photographs from all patients and, when available, fluorescein angiograms. RESULTS: In the 48 patients with type 1 Usher's syndrome, 30 (62%) showed a clinically apparent atrophic- or cystic-appearing foveal lesion, whereas in the 98 patients with type 2 Usher's syndrome, 33 (34%) had either an atrophic- or a cystic-appearing foveal lesion. Logistic regression analysis showed that the probability of exhibiting a foveal lesion in both type 1 and type 2 Usher's syndrome increases with age and that patients with type 1 Usher's syndrome are more likely to have a foveal lesion than are patients with type 2 Usher's syndrome. CONCLUSIONS: Patients with type 1 Usher's syndrome show a greater probability of having either an atrophic- or cystic-appearing foveal lesion than do patients with type 2 Usher's syndrome. This higher prevalence of foveal lesions is consistent with a previous observation that the severity of visual acuity impairment with age is greater for patients with type 1 than type 2 Usher's syndrome. These data are useful in counseling such patients as to their prognosis for central visual function. PMID- 7786222 TI - Calcific phacolysis. Salvageable vision following treatment. AB - Calcific phacolysis has been previously described histopathologically in the enucleated eyes of three patients with unilateral posttraumatic total blindness. Each eye showed dissolution of a mature cataractous lens with dispersion of calcific lens material throughout the globe. We studied a patient in whom the signs of calcific phacolysis developed 19 months following intraoperative dislocation of a cataract into the vitreous. Partial removal of calcific particles was achieved by subtotal vitrectomy and lensectomy, with subsequent penetrating keratoplasty. Corneal histopathological findings showed a deposition of calcified lens particles between Descemet's membrane and retrocorneal fibrous membrane. Despite diffuse retinal calcification, the patient's visual acuity was 20/400. To our knowledge, this is the first report of calcific phacolysis occurring after surgical dislocation of a cataract into the vitreous and wherein treatment resulted in some preservation of vision. Early diagnosis and aggressive therapy may improve the visual prognosis in this condition. PMID- 7786223 TI - Retinoblastoma. Cell of origin. AB - OBJECTIVES: To apply modern techniques of molecular cell biology and to revisit the old question of the cell of origin for retinoblastoma in hopes of gaining a better understanding of the retinoblastoma gene's antioncogenic mechanisms. METHODS: Twenty-two consecutively accessed retinoblastomas were examined with immunocytochemical techniques for numerous retinal proteins. Both single and double labeling were used. Enzyme histochemistry for carbonic anhydrase was used as well. RESULTS: Differentiated areas of the tumors contained abundant Mullerlike cells. Fleurettes stained mostly for red and green cone-specific antibodies while features of blue cones and rods predominated in areas with high cytoplasmic-to-nuclear ratios but no fleurettes. All of the differentiated neoplastic cells were either photoreceptors or Muller's cells. No other retinal cell types were found. CONCLUSIONS: The cells of retinoblastoma are capable only of bipotential differentiation, ie, Muller's cells and photoreceptors. Given this and recent findings concerning retinal embryogenesis, we argue for the rod photoreceptor as the cell of origin. A possible role for the retinoblastoma gene product is discussed. PMID- 7786225 TI - Progressive enlargement of a choroidal osteoma. PMID- 7786224 TI - Viability of human corneal endothelium following Optisol-GS storage. AB - OBJECTIVES: To evaluate endothelial viability of human corneas stored in glass vials and in viewing chambers (Alcon) for extended periods, and to compare endothelial viability of Optisol-GS-stored corneas with corneas excised from moist chamber-stored globes. METHODS: Endothelial viability was assessed using two staining techniques. Endothelium from stored corneas was stained with trypan blue combined with alizarin red S or stained with calcein AM-ethidium homodimer. Both techniques were used to determine which method is a more sensitive indicator of cytotoxic change. RESULTS: Corneas stored 4 to 21 days in Optisol-GS had a rate (mean +/- SE) of endothelial cell damage of 0.57% +/- 0.30% per day in vials and 0.69% +/- 0.27% in chambers. After storage intervals from 4 to 21 days, the Optisol-GS endothelium had an average decrease in viability of 9.5% to 16%. The endothelium of moist chamber eyes had a 44% to 59% decrease in viability after 2 to 5 days. After 24 hours, corneal endothelium of moist chamber eyes had less than 15% decrease in viability. Optisol-GS corneas stored for 35 to 56 days had greater than 50% decrease in endothelial viability. After 67 days, 95% to 100% of endothelial viability was lost. CONCLUSIONS: Corneas stored in Optisol-GS through 21 days at 4 degrees C maintain a high percentage of viable endothelial cells. There was no significant difference of endothelial viability between corneas stored in glass vials or in viewing chambers (Alcon). A 50% loss of endothelial viability occurred in moist chamber-stored corneas after 2 days and by 35 days in corneas stored in Optisol-GS. PMID- 7786226 TI - Use of intravitreal autologous blood to identify posterior cortical vitreous in macular hole surgery. AB - Surgical management of macular holes involves removal of tractional prefovial vitreous cortex. Accurately identifying this adherent tissue can potentially decrease intraoperative complications. A new, effective technique using autologous whole blood can be used to identify and facilitate separation of the posterior cortical vitreous. PMID- 7786227 TI - An eye for an eye. A simplified model for teaching. AB - We developed an easily constructed, inexpensive eye model that consists of a Styrofoam head carved out to house a slide holder, a wide-angle, clinical photographic fundus slide, a plastic face, and an anatomically correct eye. The model can be used by students and residents to learn direct and indirect ophthalmoscopy, fundus photography, and laser photocoagulation. This model gives students and residents a realistic learning experience without inconveniencing or endangering patients. PMID- 7786228 TI - Genetic and environmental influences on facial profile. AB - Observed variation in facial morphology results from the influences of both genetic and environmental factors. To investigate the role of genetic influences on variation in facial profile, lateral photographs of 23 male and 19 female monozygous (MZ), and 15 male and 22 female dizygous (DZ) twin pairs were selected from the records of the South Australian Twin Study. Soft tissue landmarks and facial profiles were identified, traced and digitized. Linear and angular measures defined by the landmarks were calculated and a series of Fourier functions derived to describe the facial profiles. These Fourier amplitudes were interpreted in terms of the specific regions which they represented. Correlations within MZ pairs were consistently higher than within DZ pairs for both the facial dimensions and the Fourier amplitudes, providing evidence of significant genetic contribution to facial convexity, facial height and facial depth. Variability in nose and lip morphology appeared to be under stronger environmental influence. PMID- 7786230 TI - Extrusion of root-filled incisors in beagles--a light microscope and scanning electron microscope investigation. AB - The response of the periodontal ligament to orthodontic extrusion of the incisor of a beagle was examined with light microscope and scanning electron microscope techniques. The ligament morphology was slightly altered by the procedure but was essentially normal. Teeth that were extruded and retained for 12 weeks exhibited partial relapse. Where a full thickness mucogingival flap was raised and immediately replaced in lieu of retention, continued extrusion was observed. Root resorption was observed at the interproximal region of the cervical third in three out of five specimens. The resorption had been repaired with cellular cementum. PMID- 7786229 TI - Donor variability in the proliferation of human dental pulp fibroblasts. AB - Fibroblasts were isolated from human dental pulps of healthy third molars from 49 donors of ages ranging from 17 to 68. Significant variability was noted in the success of obtaining primary cultures from these pulps. Variability between the various cultures was also observed in the reliability of maintaining subcultures of the primary cultures as well as recovery from frozen stocks of established cell lines. Of the original 49 explant cultures studied, only three survived long term passage and freezing. In addition to difficulties and variability in establishing cell lines, the human pulp fibroblasts also showed great variability in proliferative activity which could not be accounted for by donor age, source, or passage number. These findings highlight significant difficulties in establishing reliable human pulp fibroblast cultures and the need for great care in interpreting any in vitro data. PMID- 7786231 TI - Degradative enzymes of oral streptococci. AB - Members of the Streptococcus sanguis group (SSG) and Streptococcus milleri group (SMG) were screened for their ability to produce glycosidase, arylamidase (peptidase), protease, dextranase and glycosyltransferase activities. Species within each group produced unique patterns of activity. The most commonly produced glycosidases were beta-D-glucosidase, beta-D-galactosidase, N-acetyl beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase and the least commonly produced glycosidase activity was beta-fucosidase with Streptococcus intermedius (SMG) being the only species capable of producing the activity. For arylamidase activity, the most commonly produced type was lysine-arylamidase. Glycosidase and arylamidase activities were localized to particular sub-cellular fractions. alpha-galactosidase was found only in culture supernatant fluids whereas N-acetyl-beta-D-glucosaminidase was found in all fractions; the culture supernatant, cell wall, cell membrane and cytoplasm. No arylamidase activity was seen in culture supernatants. Phe-arg-arylamidase was found only in cytoplasmic fractions whereas val-pro-argarylamidase was found in cell walls, cell membranes and cytoplasmic fraction. Protease activity was measured as the degradation of bovine serum albumin (BSA) and casein. Casein was degraded by a number of strains whereas no species/strains were able to degrade BSA. Streptococcus intermedius, Streptococcus constellatus (SMG), Streptococcus mitior and Streptococcus defectivus (SSG) were the only species that produced hyaluronidase and no species produced chondroitin sulphatase. The groups were also examined for their abilities to produce glycosyltransferase and dextranase. Strep. sanguis, Streptococcus gordonii, Streptococcus mitis and Streptococcus oralis produced glucosyltransferase and, with the exception of the latter species, fructosyltransferase. No species within the SMG was capable of producing either glycosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786232 TI - Mouthguard protection in sports injury. PMID- 7786233 TI - Effects of splint therapy in TMJ dysfunction: a study using magnetic resonance imaging. AB - This pilot study was undertaken to correlate clinical and MRI diagnoses in seven symptomatic TMJ dysfunction patients and to account, if possible, for the clinical improvement in the signs and symptoms after the use of a maxillary stabilizing splint. The symptomatic TMJs were evaluated by means of MRI prior to splint insertion. Sagittal open/closed, and coronal closed images were obtained with a 0.3 T Fonar MR Scanner. A follow-up MRI was taken after three months of splint therapy for the purposes of a comparative study. All subjects responded positively even at the early phase of splint treatment. By the end of the three month period, six subjects experienced full remission of pain in the TMJ and associated masticatory muscles with one subject experiencing only partial remission following therapy. Baseline MRI study revealed that only three subjects had anterior disc displacement while the other four subjects had normal disc/condyle relationships and morphology. In the follow-up MRI study, there were no signs of recapture of the three anteriorly displaced discs despite there being evidence of improved jaw movement and remission of pain symptoms. The use of MRI in this preliminary study indicates that some but not all TMJ pain dysfunction syndromes are caused by internal derangements of the joint. A larger MRI study using the same clinical parameters is indicated for future research. PMID- 7786234 TI - A comparison of the effects of Nd:YAG and Ho:YAG laser irradiation on dentine and enamel. AB - This preliminary study was undertaken to investigate the effects of Nd:YAG and Ho:YAG lasers on enamel and dentine of extracted teeth. The Ho:YAG laser (spot size 250 microns, energy density 4160 J/cm2) produced a cleaner puncture in dentine with less melting of the surrounding tissue than did the Nd:YAG laser (spot size 20 microns), energy density 50,000 J/cm2), which produced considerable melting and recrystallization of dentine and was more difficult to control. It was possible to cut enamel and dentine with both lasers, but considerable melted and recrystallized enamel was produced. From the limited observations of this study it appears that the Ho:YAG laser is more suitable for cutting both enamel and dentine than the Nd:YAG laser. More work needs to be done to ascertain the effect on enamel and dentine of modification of the parameters of both lasers. PMID- 7786235 TI - The choice of irrigant during hand instrumentation and ultrasonic irrigation of the root canal: a scanning electron microscope study. AB - The purpose of this study was to investigate the use of 4 per cent sodium hypochlorite and 15 per cent EDTAC, either alone or in conjunction, as irrigants during hand instrumentation and ultrasonic irrigation of the root canal. Thirty six extracted human teeth, each with a single, straight root 21-25 mm long were hand-instrumented through a clinical access cavity to file size 40. One millilitre of the test irrigant was used after each instrument size. Canal debridement was completed with an intermittent flush irrigation technique with one or both of the test irrigants activated by ultrasound at a medium effective power output. The specimens were sectioned longitudinally, viewed in a scanning electron microscope and scored for the presence or absence of debris and smear layer at levels less than 1 mm, 5 mm, and 10 mm from the apical seat. Under the conditions of this experiment the most effective regime was irrigation with 1 mL EDTAC after each instrument size, followed by two 30 second exposures to ultrasound+EDTAC then four 30 second exposures to ultrasound + 4 per cent sodium hypochlorite. The specimens in this group were free from retained pulp tissue and superficial smear layer, had the lowest debris scores at the < 1 mm and 5 mm levels, and the lowest total debris score. All of the techniques tested produced smear-free canals at the 10 mm level. PMID- 7786236 TI - Oral Candida albicans from patients infected with the human immunodeficiency virus and characterization of a genetically distinct subgroup of Candida albicans. AB - Candida albicans has been shown to vary in its phenotypic expression with the progression of human immunodeficiency virus (HIV) infection. This study was designed to investigate whether in Category IV HIV infected patients (CDC, Atlanta, USA) these phenotypic changes were related to changes in the genetic strain of the organism. Isolates of C. albicans were obtained from 45 patients with HIV infection during the progression of their disease as determined by percentage T4 lymphocyte count. Isolates were strain differentiated using two methods. In 67 per cent of the patients a single strain of C. albicans, as determined by the DNA analysis, was isolated from each individual over the experimental period. The phenotypic expression of the genetically identical strains isolated from each patient varied considerably over the experimental period with the morphotype 754 being predominant. These results showed that the genotype of C. albicans isolated persisted in the majority of HIV infected individuals, but that the phenotypical expression of this strain changed. A finding in this study was that 18 strains of C. albicans had DNA which did not hybridize to the probe used. These strains were analysed for the presence of two other C. albicans specific DNA segments using PCR. The probe 27A hybridizing strains yielded PCR products which differed from the non-hybridizing strains. Five of these genetically atypical C. albicans strains and 98 of the C. albicans strains were then analysed for purported virulence factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786237 TI - A questionnaire survey of dentists regarding knowledge and perceived competence in resuscitation and occurrence of resuscitation emergencies. AB - Little information has been published on the knowledge and perceived competence of dentists in resuscitation or the occurrence of resuscitation emergencies in dental practice. Further, no such surveys have been done in Australia. A postal survey was therefore devised and the names of 350 dentists were randomly selected from the Australian Dental Association national membership registry. The response rate was approximately 45 per cent and the main results included: just under half of the respondents felt they were competent in basic resuscitation at the time of graduation, that is, in expired air resuscitation (EAR) and cardiopulmonary resuscitation (CPR); just less than two-thirds had undertaken resuscitation training since graduation; about three-quarters felt they would be able to perform EAR and almost two-thirds felt they would be able to perform CPR; almost 90 per cent gained a satisfactory score in a Resuscitation Quiz included in the survey; and just over 5 per cent had had to resuscitate a patient. PMID- 7786238 TI - Smoking-related beliefs and behaviour among adults with asthma in a representative population sample. AB - BACKGROUND: Smoking and exposure to environmental tobacco smoke are inadvisable for adults with asthma. AIMS: To determine the smoking prevalence and daily smoking rate of asthmatics and compare smoking-related beliefs and behaviours among smokers with and without asthma. To compare beliefs of asthmatics about passive smoking and asthma, how many are exposed at home and what they do when they are exposed, with people who do not have asthma. METHODS: A representative population survey of 3019 South Australian adults aged 15 years and older interviewed in their own homes in late 1992. RESULTS: Twenty-eight per cent of asthmatics were smokers; mean daily smoking rate was 17.6. Asthmatics had similar patterns of smoking, readiness to quit and quit attempt histories as people without asthma. More than 40% of smokers with asthma did not perceive that smoking had greatly affected their health, over half did not believe they were at risk in future and two-thirds did not think future health problems would be serious. Among non-smokers, despite being more convinced of the effects of passive smoking on asthma, and being more concerned about exposure, those with asthma were no more likely to take protective action in response to actual or imminent exposure than those without asthma. One in ten non-smokers with asthma were exposed to smoking at home. CONCLUSIONS: The smoking habits of adults with asthma are cause for concern, with many asthmatic smokers perceiving they are not personally at risk from their smoking. Health education principles should be used by health professionals caring for asthmatic smokers to guide the selection and delivery of smoking cessation strategies. Prevailing restrictions on indoor smoking play an important role in protecting the respiratory health of non smokers with asthma. PMID- 7786240 TI - Comparative hospitalisation and mortality rates of aboriginal and non-aboriginal Western Australians in their sixth and seventh decades. AB - BACKGROUND: Aboriginals have higher hospitalisation and mortality rates and die, on average, about 15 years earlier than non-Aboriginals in Western Australia (WA). AIMS: To investigate Aboriginal morbidity and mortality rates in WA in comparison with the rest of the population, with particular reference to the ages of 50 to 65 years. METHODS: Mortality rates from 1983-1989 inclusive for Aboriginals and non-Aboriginals in WA were compared. Major causes of Aboriginal mortality in males and females were matched to the ages at which similar rates from the same causes occurred in non-Aboriginals. Rate ratios (Aboriginal:non Aboriginal) for causes of death at ages 60-64 years were determined. Hospitalisation rates for Aboriginal and non-Aboriginal people aged 50-64 years in WA in 1988 were used to estimate hospitalisation rate ratios. RESULTS: Hospitalisation rates in WA were much higher among 50 to 64 year old Aboriginals than non-Aboriginals for most diseases, particularly for infectious and parasitic diseases, and injury and poisoning. Admissions for circulatory diseases were double to four times as frequent among Aboriginals. The main causes of deaths in Aboriginal males were circulatory diseases, injury and poisoning, respiratory diseases, neoplasms, and digestive diseases; in Aboriginal females the main causes of deaths were circulatory diseases, neoplasms, diabetes, respiratory diseases, and injury and poisoning. Except for neoplasms, deaths from these causes occurred among 50-54 year old Aboriginals at rates that were experienced by non-Aboriginal people ten to 30 years later in life. These results underline special needs of the Aboriginal population that have not been adequately met by appropriate services. PMID- 7786239 TI - Application of the Poincare plot to heart rate variability: a new measure of functional status in heart failure. AB - BACKGROUND: Conventional methods of quantifying heart rate variability using summary statistics have shown that decreased variability is associated with increased mortality in heart failure. However, many patients with heart failure have arrhythmias which make the 'raw' heart rate variability data less suitable for the use of summary statistical measures. AIMS: To examine the clinical potential of a new measure of heart rate variability data, presented by the Poincare plot pattern, as an adjunct to the summary statistical measures of R-R interval variability. METHODS: We used the Poincare plot pattern to display beat to-beat heart rate variability data from a group of 23 patients with heart failure and compared them with data collected from 20 healthy age-matched control subjects. The data, which consists of 2000 consecutive R-R intervals, were gathered over 20-40 minutes while the subjects rested supine in a quiet darkened room. RESULTS: The morphological classification scheme proposed reflected the functional status of patients in heart failure. There was a significant difference (chi-square = 27.5, p < 0.0001) in the different pattern types between patients with NYHA Class I and II compared to patients with NYHA Class II and IV. All healthy subjects displayed a 'cluster' type of pattern characterised by normally distributed data. Sixteen of the 23 patients in heart failure also produced data which were normally distributed but the remaining seven produced data which required careful filtering to make them suitable for analysis using summary statistics, but which could be analysed by the Poincare plot. CONCLUSIONS: The Poincare plot pattern is a semi-quantitative tool which can be applied to the analysis of R-R interval data. It has potential advantages in that it allows assessment of data which are grossly non-Gaussian in distribution, and is a simple and easily implemented method which can be used in a clinical setting to augment the standard electrocardiogram to provide 'real time' visualisation of data. PMID- 7786242 TI - A prospective study of screening upper gastrointestinal (GI) endoscopy prior to and after bone marrow transplantation (BMT). AB - BACKGROUND: Upper gastrointestinal (GI) endoscopic abnormalities are common in symptomatic bone marrow transplant (BMT) recipients but the incidence of occult gastrointestinal disease in these patients is unknown. AIMS: To examine the role of screening upper GI endoscopy before and after BMT. METHODS: Endoscopy was performed routinely on allogeneic (n = 24) and autologous (n = 17) BMT patients before transplant and at 30 and 120 days after transplant. RESULTS: Twenty-one of 41 patients (51%) had an endoscopic abnormality on one or more occasions which necessitated a change in treatment. These abnormalities were present in ten of 41 (24%) pre-transplant endoscopies, ten of 32 (31%) endoscopies at day 30 after BMT, and in seven of 22 (32%) day 120 endoscopies. Abnormalities included mucosal erosions or ulcers n = 22 endoscopies), infections (n = 5) or previously undiagnosed GI graft-versus-host disease (n = 3). Mucosal erosions or ulcers were present in eight of 28 endoscopies despite regular anti ulcer drug therapy. CONCLUSIONS: Screening upper GI endoscopy before and after BMT is generally safe and detects a high yield of significant GI abnormalities. However, it remains to be demonstrated that treatment of these lesions will improve the clinical outcome in BMT recipients without GI symptoms. PMID- 7786241 TI - Smoking more--enjoying the asthma. PMID- 7786244 TI - Anti-neutrophil cytoplasmic antibodies (ANCA) and renal diseases. PMID- 7786243 TI - Treatment of haemophilia A by continuous factor VIII infusion. PMID- 7786246 TI - Doctoring the planet: health effects of global change. PMID- 7786245 TI - The use of a highly purified factor IX (FIX) concentrate in patients with 'haemophilia B' undergoing surgery. PMID- 7786247 TI - A quantification of alcohol-related mortality in New Zealand. AB - BACKGROUND: There are no published New Zealand (NZ) studies on alcohol drinking and total mortality, despite its importance to alcohol health policy. AIMS: To estimate the proportion of NZ deaths caused or prevented by alcohol drinking. METHODS: The proportion of current alcohol drinkers from recent NZ surveys, and pooled relative risks from a review of the international literature on alcohol and mortality, were used to calculate disease-specific population attributable risks. The number of deaths caused (or prevented) by alcohol were calculated for 1987 New Zealand deaths. Person-years of life lost (or saved) were calculated using recent NZ life tables. RESULTS: The association between alcohol and total mortality was related to age. Alcohol was estimated to have caused 3.0% of all deaths among 0-14 year olds and 20.1% of deaths among 15-34 year olds, mostly from road injuries. In contrast, alcohol was estimated to have prevented 0.5% of all deaths among 35-64 year olds and 3.4% of deaths among > or = 65 year olds due to its protective effect against coronary heart disease. For all age groups, alcohol was estimated to have prevented 1.5% of deaths. However, the number of person-years of life lost among ages less than 35 years was greater than those saved in the older age groups, so that alcohol was estimated to have caused the loss of 9525 person-years of life for all ages combined. CONCLUSIONS: The adverse effects of alcohol on total mortality are confined to age groups less than 35 years. Public health policy to minimise deaths from alcohol should be concentrated on this group. PMID- 7786248 TI - Trigeminal sensory neuropathy induced by interferon-alpha therapy. PMID- 7786249 TI - Stroke among Australian aboriginals in Perth, WA, 1988-1992. PMID- 7786250 TI - Disseminated histoplasmosis: successful maintenance therapy with oral fluconazole. PMID- 7786251 TI - Severe salicylate poisoning associated with the intake of Chinese medicinal oil ('red flower oil') PMID- 7786253 TI - Anaphylactic reaction to intravenous cyclophosphamide. PMID- 7786254 TI - Interaction of 5-fluorouracil with folates. PMID- 7786252 TI - Acute renal failure due to sulphadiazine in a patient with acquired immunodeficiency syndrome (AIDS) PMID- 7786255 TI - Cytomegalovirus appendicitis in a patient with acquired immune deficiency syndrome (AIDS) PMID- 7786257 TI - Helicobacter pylori in peptic ulcer disease. PMID- 7786256 TI - Asthma spoils from polyunsaturated oils? PMID- 7786258 TI - The Royal Australasian College of Surgeons and trauma care. AB - This presentation is an account of the involvement of the Royal Australasian College of Surgeons in trauma care over the past 25 years. In October 1969 a 3 day seminar was held at the College entitled 'The Management of Road Traffic Casualties'. This was in response to an increasing demand for the College to combat the devastating effects resulting from road traffic accidents. By the mid 60s road trauma in Australia and New Zealand, as seen in other fully motorized countries, had reached epidemic proportions. Those directly involved in the care of surgical emergencies were aware of the frequency and severity of road trauma which was striking all sections of the community. Unlike the USA, Australia was not troubled by a high incidence of penetrating injuries due to guns and knives. PMID- 7786260 TI - Bone scanning in the multiply injured patient. AB - A prospective study was undertaken to evaluate the role of radionuclide bone scanning in the management of patients with multiple injuries. During a 7 month period, 14 patients with multiple injuries underwent a bone scan in order to identify occult skeletal injuries. All of the patients had new injuries diagnosed. The majority of new injuries occurred either in a limb in which an injury had already been diagnosed at presentation, or in the chest. Such findings are consistent with previously published data. Infrequently, there was a change in management of the patients in this series following the bone scan. PMID- 7786259 TI - Hepatic artery chemotherapy for colorectal liver metastases. AB - Fifty per cent of patients with colorectal cancer develop hepatic metastases but only a minority are candidates for potentially curative surgical resection. Hepatic artery chemotherapy (HAC) has been used to treat patients with non resectable metastases confined to the liver. Although response rates to HAC have been shown to be higher than response rates to systemic chemotherapy, the advantage in terms of survival has been debated. Furthermore, HAC requires surgical catheter placement which adds to the cost and morbidity of treatment. There have now been eight prospective randomized trials of HAC vs intravenous chemotherapy and/or supportive therapy. The present paper analyses the results of these trials with particular reference to survival. Surgical morbidity, treatment related toxicity and cost are also discussed. PMID- 7786261 TI - Penetrating thoracoabdominal injuries with arrows: experience with 63 patients. PMID- 7786262 TI - The influence of other diseases upon the outcome of colorectal cancer patients. AB - Little attention may be paid during follow up of colorectal cancer patients to other medical problems because the follow up is normally focused upon the diagnosis of recurrence and the detection of metachronous neoplasms. Attention directed at improving the medical condition of patients would be justified if it were shown that other diseases had a significant effect upon survival. Review of a selected consecutive series of 207 patients included collection of data about variables relating to demography, pathology, presentation, smoking, present and past health, performance, surgery, complications, length of stay, mortality, follow up and cause of death. Significance of relationships between medical and surgical problems and the outcome was determined by analyses of variation. Medical problems were present in 79% of patients; correlated with advancing age. Medical problems were not associated with complications, or with inpatient death. Previous cerebrovascular accident, dementia, limited mobility and increasing numbers of problems were associated with prolonged stay. Prolongation of stay, however, was related mainly to surgical complications. Smoking, which was present in 50% of patients, did not alter performance status, stage or substage, stay or survival significantly. Smoking and respiratory complications were associated significantly. Patients with heart or peripheral vascular disease had significantly poorer survival (P = 0.007) than those without those problems. Survival was reduced significantly for patients known to have diabetes, cardiovascular and cerebrovascular disease and limited mobility. Other malignant neoplasms were responsible for 18% of deaths which were unrelated to colorectal cancer. Residual or recurrent colorectal cancer had a more rapid adverse influence upon outcome than did medical problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786264 TI - A comparative study of two types of latex surgical gloves in elective orthopaedic surgery. AB - Glove perforation during surgery represents a potential risk of infection for the surgeon. The authors postulated that thicker latex gloves may offer greater protection. The perforation rates for the Ansell Gammex glove and the thicker Baxter Triflex gloves were compared in single- and double-glove usage and no difference was found between the two brands, in either usage. The authors recommend double-gloving for all orthopaedic operations with regular glove changes during major procedures. PMID- 7786263 TI - 99mTechnetium labelled leucocyte scanning in acute lower abdominal pain: can it reduce the negative appendectomy rate? AB - While the incidence of 'negative' appendectomy has long been justified as a necessary evil in the management of acute appendicitis, attempts to improve diagnostic accuracy have met with mixed results. In a prospective study of 34 selected patients who presented with acute lower abdominal pain the potential role of 99mTechnetium labelled leucocyte scanning in the diagnosis of acute appendicitis has been evaluated. Patient management was not based on the result of the nuclear scan. The clinical outcome was correlated with the scan diagnosis. There was one false positive and one false negative scan result with respect to the clinical diagnosis of appendicitis yielding a sensitivity of 90% and a specificity of 96%. 99mTechnetium labelled leucocyte scanning may have an important role in the assessment of selected patients presenting with acute lower abdominal pain. PMID- 7786265 TI - Limb length discrepancy in congenital talipes equinovarus. AB - A retrospective analysis was performed to establish the prevalence and clinical significance of limb length discrepancy in congenital talipes equinovarus. Of 536 patients with the diagnosis of congenital talipes equinovarus, 259 were unilaterally affected and 277 bilaterally affected. Fifty-eight patients were identified with limb length discrepancy greater than 0.5 cm. Forty-six patients had unilateral foot deformity and in 12 cases that was bilateral. This represented a prevalence of documented limb length discrepancy in 18% of unilateral cases and 4% of bilateral cases. The discrepancy resulted in a surgical procedure to equalize the limb lengths in fourteen unilateral cases (5%). A further six unilateral cases were deemed likely to require limb length equalization, increasing the rate to 8%. Only three bilateral cases required or will require surgery for equalization (1%). There was a weak but significant correlation between the number of operations undergone and the magnitude of discrepancy. The tibia was as important in its contribution to the shortening in these patients as the foot. A total of 89% unilateral cases studied had at least 0.3 cm of tibial shortening and 43% had ipsilateral femoral shortening of at least 0.3 cm. PMID- 7786266 TI - V-Y advancement hamstring myocutaneous island flap repair of ischial pressure ulcers. AB - Thirty-seven ischial pressure ulcers were repaired in 27 patients (eight quadriplegic, 19 paraplegic) between 1988-1993 using the V-Y advancement hamstring myocutaneous island flap. Twenty-one ulcers (57%) arose de novo and 16 were recurrent, with five patients having bilateral ulcers. The average duration of the ulcer was 5 months (range 1-30). All ulcers extended through the deep fascia (clinical grade IV), with the average diameter being 4.7 cm (range 2-10). There were four major flap complications (11%). All but one of the ulcers healed at discharge (97%). Mean follow up was 20 months (range 5-54) in 21 patients (78%), with six patients being lost to follow up. Seven of the 21 (33%) patients developed recurrent ulcers, with four of these having flap re-advancement with successful healing, and one patient having two re-advancements. Overall, 18 of the 21 (86%) patients with follow up had healed ulcers at time of follow up. The V-Y advancement hamstring myocutaneous island flap is versatile, reliable, easy to perform, has few complications, and can be re-advanced in the event of recurrence. PMID- 7786267 TI - Morbidity and mortality after abdominal aortic surgery in a population of patients with high cardiovascular risk. AB - Postoperative myocardial infarction is a major risk factor in patients undergoing abdominal aortic surgery. Correction of cardiac ischaemia prior to abdominal aortic surgery improves outcome. The morbidity and mortality of 639 consecutive patients were reviewed from an area with poor access to cardiac surgery, operated upon in a single tertiary referral hospital for aortic aneurysm or aortobifemoral grafting. A total of 101 patients with ruptured aortic aneurysm who survived to reach the intensive care unit experienced a hospital mortality of 29%. Multiorgan failure was the cause of death in 48% and postoperative myocardial infarction in 31%. Of the 253 patients with intact aortic aneurysm, which included elective and urgent resection, the mortality was 9%. There was a high incidence of uncorrected pre-operative ischaemic heart disease and myocardial infarction was the major cause of death (62%). Pre-operative myocardial infarction was predictive of postoperative cardiac morbidity and mortality. Of the 285 patients undergoing aortobifemoral grafting the mortality was 3% despite a high incidence of pre operative ischaemic heart disease. Further reductions in postoperative death from ruptured aortic aneurysm must await improved screening to diagnose and treat the aneurysm before rupture. In patients operated upon electively, improved pre operative cardiac screening and coronary bypass grafting where appropriate, especially for patients with aortic aneurysm and previous myocardial infarction, may further reduce peri-operative mortality. PMID- 7786268 TI - Video-assisted thoracoscopic lobectomy: a word of caution. AB - Advances in video-assisted thoracoscopic (VAT) surgery allow it to assume an increasingly important therapeutic role. Two successful VAT lobectomies (left upper lobe and right lower lobe) were performed in patients with stage I adenocarcinoma. An 8 cm access minithoracotomy for hilar dissection and subsequent specimen delivery was used. Routine mediastinal node sampling was performed thoracoscopically as would be done conventionally. Video-assisted thoracoscopic lobectomy of the right upper lobe was attempted in another patient but he required emergency conversion to open thoracotomy because of bleeding from mechanical failure of the vascular staple-cutter. Although VAT lobectomy is feasible technically, attention to detail is important when mechanical devices are used to minimize the chance of malfunctioning. Once disaster occurs the surgeon should be capable of dealing with the consequences. PMID- 7786269 TI - 'To record his voice': two memorials to surgeon Walter Scott (1787-1854), first surgeon of northern Australia. PMID- 7786270 TI - Autologous blood donation in total hip replacement. PMID- 7786271 TI - Severe bronchospasm during rectal carcinoid resection. AB - The manifestations of carcinoid syndrome result from a variety of hormones secreted by the carcinoid tumour. The minority of patients with carcinoid tumour suffer bronchospasm and flushing. In this report the possibility of carcinoid syndrome in a patient who developed severe bronchospasm during operative manipulation of his rectal carcinoid is discussed. PMID- 7786272 TI - Sporting 'groin strains': not always muscular! AB - A gluteal artery pseudoaneurysm presenting as a 'groin strain' following minor trauma is reported. Diagnosis was made by CT scan and arteriography. Treatment was with superselective catheterization and microcoil embolization. PMID- 7786273 TI - Intracranial invasion from a primary adenocarcinoma arising in the middle and external ear. AB - Cerumenal adenocarcinoma is a rare neoplasm arising from the modified sweat glands of the ear. Before the diagnosis of primary tumour is made, a thorough search must be undertaken to exclude the possibility of metastatic disease, which occurs more commonly. Benign adenoma can also occur and this may be identical histologically to the malignant variety. The presence of local invasiveness may be the only differentiating feature. Aggressive local resection followed by postoperative radiotherapy form the cornerstone of management. Individuals treated with radiotherapy alone have a life expectancy of less than 12 months whereas cures have been reported with radical surgery. PMID- 7786274 TI - Endoscopic treatment of a giant ileal conduit calculus. AB - A giant ileal conduit calculus is an uncommon complication of urinary diversion, with few recent reports present in the English literature. To date all described instances have necessitated treatment by laparotomy. The first reported successful management of such a condition by purely endoscopic means is reported. PMID- 7786276 TI - [Two mesenchymal tumor cell lines for the determination of natural killer (NK) cell activity in the peripheral blood of dogs]. AB - The two mesenchymal cell lines K1 and K6 were established from round cell tumours located at the lips of two dogs. Both cell lines were characterized as being of myelomonocytic origin by morphological, cytochemical, immunocytochemical and functional criteria. In the 51chromium release assay (effector/target cell ratio 100/1) the K6-cell line revealed a mean cytotoxic sensitivity of 53.6% and thus showed a susceptibility similar to that of the epithelial CTAC line (57.8%). The K1-cell line exhibited less cytotoxic activity (41%) when incubated for 14 h, but showed results comparable to the K6-cell line, when the incubation time was reduced to 8 h. PMID- 7786275 TI - [Mammary carcinoma in female dogs: a new routine diagnosis by the detection of occult micrometastases in the regional lymph nodes]. AB - It was here to find an antibody staining either the epithelial tissues of the canine mammary or the tumor cell embolisms and metastases in their regional lymph nodes. 77 formalin-fixed and paraffin-embedded mammary carcinomas and their regional lymph nodes were examined by immunocytochemical technique, all of them free of metastases in routine haematoxylin and eosin (HE) staining. To compare the two methods two serial sections were cut of three parts of the lymph nodes. One was stained with the antibody AE1, which reacts with cytokeratin subtype I/A, in the SEQUENZA by APAAP-method, the other with HE. In 84.4% of all 77 lymph nodes tumour cell embolism and/or micrometastases were detected. Comparing the two methods we found that in HE-staining it was only possible to detect two thirds of all micrometastases containing more than 50 tumor cells. Smaller micrometastases were suspicious in a few cases, the majority could not be detected at all. PMID- 7786277 TI - [Detection of distemper virus N protein RNA in the brain of dogs with spontaneous distemper encephalitis using a digoxigenin-labeled, double-stranded DNA probe for in situ hybridization]. AB - A digoxigenin-labelled dsDNA-probe of 287 basepairs length complementary to the nucleoprotein-gene of canine distemper virus (CDV) was generated by the polymerase-chain-reaction. The dsDNA-probe hybridized specifically with base sequences of 8 different CDV strains, whereas no hybridization was observed with a porpoise and a canine parainfluenza virus and only a weak signal was obtained with measles virus. In formalin-fixed, paraffin-embedded brain sections of 35 immunohistologically CDV antigen positive dogs with spontaneous distemper encephalitis CDV-RNA could be detected in 25 cases by in situ hybridization. The reason for the lack of RNA detection in some immunohistologically positive dogs may be due to the low stability of DNA-RNA-hybrids. Degradation of RNA by RNAses or diffusion out of autolysed cells can not be excluded. PMID- 7786278 TI - [Clostridium bifermentans infection in grass carp (Ctenopharyngodon idella)]. AB - The outbreak of an infection with Clostridium bifermentans in grass carp (Ctenopharyngodon idella) from a polyculture fish pond is documented. PMID- 7786280 TI - [Pulmonary emboli of skin and hair particles after intravenous injections]. AB - Among 1422 Sprague-Dawley rats treated daily for 28 consecutive days by i.v. injections, 779 animals (55.8%) showed lesions at the site of injection. 381 rats (26.8%) had pulmonary emboli with fragments of hair or skin in arterial thrombi or in giant cell granulomas. 6 weeks after cessation of treatment lesions were still found in lungs from 5 of 90 rats (5.6%) allowed to recover. In 8 of 64 Himalayan rabbits (12.5%) given 28 injections into ear veins pulmonary embolism was observed. Among 184 rhesus and cynomolgus monkeys treated daily for 28 consecutive days by injection into cephalic or saphenous veins, 167 monkeys (91%) showed lesions at the site of injection, 14 animals (7.6%) had pulmonary emboli with fragments of hair and skin in arterial thrombi or giant cell granulomas. PMID- 7786279 TI - [The significance of FeLV infection for diseases in necropsied cats]. AB - Persistent FeLV infection was demonstrated in more than 3000 necropsied cats by an immunohistological method. The findings were associated with the diagnoses established by means of post-mortem examination, histopathological, bacteriological, virological, and parasitological investigations. Statistically significant differences between FeLV-positive and FeLV-negative cats in the relative risk for certain lesions could be demonstrated for the first time. As a consequence, the importance of FeLV infection for the development of certain lesions in cats is to be seen under new aspects for some diagnoses. The relative risk for development of anemia, e.g., is only slightly increased in FeLV-positive animals whereas the relative risk for focal myocardial necrosis and coccidiosis is elevated tremendously in these cats. The relative risk for some lesions and diagnoses is much higher in FeLV-negative cats than in FeLV-positive animals. This is true, e.g., for myocardiopathy and hemorrhagic cystitis. PMID- 7786281 TI - [Elevation of 7-dehydrocholesterol concentrations in serum and liver and pericentral peroxisome proliferation in hepatocytes of rats after inhibition of cholesterol biosynthesis by BM 15,766]. AB - Sprague-Dawley rats of both sexes were treated for three months with BM 15,766, an inhibitor of cholesterol biosynthesis in conjunction with standard or high-fat and high-cholesterol diets. In serum and livers of all drug-treated rats lowered cholesterol concentration associated with an increase of 7-dehydrocholesterol (7 DHC) was found. Electron microscopy of the liver showed a distinct proliferation of peroxisomes and an increase of dumb-bell shaped mitochondria in the pericentral zone 3. Abnormal-shaped peroxisomes with DAB-negative loops attached to their membranes were found in the intermediate zone 2. These alterations were more accentuated in drug-treated rats fed standard diet, then in treated rats receiving a high-fat and high-cholesterol diet. The observations demonstrate, that the increase of 7-DHC is due to the inhibition of 7-DHC-delta 7-reductase by BM 15.766 and emphasize the zonal heterogeneity of hepatocytes. The relevance of these observations for the investigation of the human Smith-Lemli-Opitz syndrome, in which also decreased plasma-cholesterol levels and an increase of 7-DHC were reported, is discussed. PMID- 7786282 TI - [Intraosseous epidermoid cysts of the toe phalanx in dogs]. AB - Out of 1057 amputated canine toes with tumours, tumour-like or other lesions, 17 cases were histopathologically diagnosed as epidermoid cysts of the terminal phalanx (EP). They were accompanied by osteolysis, reactive bone formation and chronic inflammation of phalanx 3. Extension of reactive changes to the phalangeal joint and phalanx 2 was less frequent. Various breeds were involved. There was no breed predisposition. The average age was 10.8 years; the male female ratio 2.4:1. Nine EP were located on the forelimbs, 4 on the hindlimbs. In 4 cases location was unknown. Toes 4 and 5 were most frequently affected. A traumatic origin is suspected. PMID- 7786284 TI - Precursor cell types in the germinal zone of the cerebral cortex. AB - Retroviral lineage tracing experiments suggest that the cortical ventricular zone is composed of a mixture of precursor cell types. The majority generate a single cell type (neurones, astrocytes or oligodendrocytes) and the remainder generate neurones and a single type of glial cell. Pluripotential precursor cells, that have the ability to generate all three cell types, are not observed. A recent paper, however, reports that when single ventricular zone cells are cultured in isolation, a small percentage of these cells are pluripotential. This review will discuss what this knowledge tells us about cortical development. PMID- 7786283 TI - Specifying the target identity of motoneurons. AB - In the vertebrate spinal cord, motoneurons are clustered into longitudinal columns in agreement with the targets they innervate. Motoneurons within each column acquire properties early in development that ensure their axons navigate to appropriate targets, but how this target identity is specified is unknown. Recently, Tsuchida et al. described the expression of putative regulatory genes within motor columns in the chicken spinal cord. Combinations of LIM-family homeobox genes differentially mark columns that project to distinct target groups. Expression precedes column formation and axon outgrowth, making these genes candidates for specifying the target identity of motoneuron groups. PMID- 7786286 TI - Determinants of blastomere identity in the early C. elegans embryo. AB - Genetic and molecular studies of development in Caenorhabditis elegans have identified regulators that appear to control pattern formation in the cellularized nematode embryo. Two genes, skn-1 and pie-1, are required for specifying the different identities of two sister blastomeres in a 4-cell embryo, called P2 and EMS. The skn-1 gene encodes a DNA binding protein that may control blastomere development by regulating transcription in EMS and its descendants. ABa and ABp, the other two sisters in a 4-cell embryo, are influenced to develop differently by cell signaling events that require the two genes apx-1 and glp-1. In this review, I summarize evidence that some or all of these genes may encode embryonic determinants of blastomere identity. PMID- 7786285 TI - Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. AB - Ras proteins function as critical relay switches that regulate diverse signaling pathways between cell surface receptors and the nucleus. Over the past 2-3 years researchers have identified many components of these pathways that mediate Ras activation and effector function. Among these proteins are several guanine nucleotide exchange factors (GEFs), which are responsible for directly interacting with and activating Ras in response to extracellular stimuli. Analogous GEFs regulate Ras-related proteins that serve other diverse cellular functions. In particular, a growing family of proteins (Dbl homology proteins) has recently been identified, which may function as GEFs for the Rho family of Ras-related proteins. This review summarizes our current knowledge of the structure, biochemistry and biology of Ras and Rho family GEFs. Additionally, we describe mechanisms of GEF activation of Ras in signal transduction and address the potential that deregulated GEFs might contribute to malignant transformation through chronic Ras protein activation. PMID- 7786288 TI - Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. AB - Reversible acetylation at the epsilon-amino group of lysines located at the conserved domain of core histones is supposed to play an important role in the regulation of chromatin structure and its transcriptional activity. One promising strategy for analyzing the precise function of histone acetylation is to block the activities of acetylating or deacetylating enzymes by specific inhibitors. Recently, two microbial metabolites, trichostatin A and trapoxin, were found to be potent inhibitors of histone deacetylases. Trichostatin A reversibly inhibits the mammalian histone deacetylase, whereas trapoxin causes inhibition through irreversible binding to the enzyme. The histone deacetylase from a trichostatin A resistant cell line is resistant to trichostatin A, indicating that the enzyme is the primary target. Both of the agents induce a variety of biological responses of cells such as induction of differentiation and cell cycle arrest. Trichostatin A and trapoxin are useful in analyzing the role of histone acetylation in chromatin structure and function as well as in determining the genes whose activities are regulated by histone acetylation. PMID- 7786289 TI - A radical approach to enzyme catalysis. AB - Free radicals are generally perceived as highly reactive species which are harmful to biological systems. There are, however, a number of enzymes that use carbon-based radicals to catalyse a variety of important and unusual reactions. The most prominent example is ribonucleotide reductase, an enzyme which is crucial for the synthesis of DNA. In general, radicals are used to remove hydrogen from unreactive positions in the substrate, and in this way the substrate is activated to undergo chemical transformations that would otherwise be difficult to achieve. Several different mechanisms have evolved which allow enzymes to generate and maintain radicals in increasingly aerobic environments. An unexpected finding is the existence of stable protein-based radicals, residing on a variety of amino-acid side chains, which serve to link the radical generating and catalytic sites and to store the radical between turnovers. PMID- 7786287 TI - Seminal plasmin. AB - The importance of seminal plasma in fertilization was appreciated as early as 1677 and would thus hardly seem a source for the search of antibacterial agents. The observation that seminal plasma had the ability to inhibit the growth of microorganisms in 1940 led to a systematic search for molecules possessing antimicrobial activity in addition to factors that might have a role in reproductive physiology. Extensive investigations led to the discovery in bovine seminal fluid of a 47-residue peptide, possessing potent antimicrobial activity as well as calcium transport modulatory properties in bovine sperm. We describe in this article the two, apparently unrelated, biological activities of this peptide. PMID- 7786291 TI - Model systems in developmental biology. AB - The practical criteria by which developmental biologists choose their model systems have evolutionary correlates. The result is a sample that is not merely small, but biased in particular ways, for example towards species with rapid, highly canalized development. These biases influence both data collection and interpretation, and our views of how development works and which aspects of it are important. PMID- 7786290 TI - The channels model of nuclear matrix structure. AB - The specificity of eukaryotic DNA organization into loops fixed to the nuclear matrix/chromosomal scaffold has been studied for more than fifteen years. The results and conclusions of different authors remain, however, controversial. Recently, we have elaborated a new approach to the study of chromosomal DNA loops. Instead of characterizing loop basements (nuclear matrix DNA), we have concentrated our efforts on the characterization of individual loops after their excision by DNA topoisomerase II-mediated DNA cleavage at matrix attachment sites. In this review the results of applying this mapping approach are compared with the results and conclusions from studies of nuclear matrix DNA. An attempt is also made to reconsider all data about the specificity of DNA interactions with the nuclear matrix and to suggest a model of spatial organization of the eukaryotic genome which resolves apparent contradictions between these data. PMID- 7786292 TI - A model for repair of radiation-induced DNA double-strand breaks in the extreme radiophile Deinococcus radiodurans. AB - The bacterium Deinococcus (formerly Micrococcus) radiodurans and other members of the eubacterial family Deinococaceae are extremely resistant to ionizing radiation and many other agents that damage DNA. Stationary phase D. radiodurans exposed to 1.0-1.5 Mrad gamma-irradiation sustains > 120 DNA double-strand breaks (dsbs) per chromosome; these dsbs are mended over a period of hours with 100% survival and virtually no mutagenesis. This contrasts with nearly all other organisms in which just a few ionizing radiation induced-dsbs per chromosome are lethal. In this article we present an hypothesis that resistance of D. radiodurans to ionizing radiation and its ability to mend radiation-induced dsbs are due to a special form of redundancy wherein chromosomes exist in pairs, linked to each other by thousands of four-stranded (Holliday) junctions. Thus, a dsb is not a lethal event because the identical undamaged duplex is nearby, providing an accurate repair template. As addressed in this article, much of what is known about D. radiodurans suggests that it is particularly suited for this proposed novel form of DNA repair. PMID- 7786293 TI - Chance and longevity. PMID- 7786294 TI - Use of pure antioestrogens to elucidate the mode of action of oestrogens. PMID- 7786295 TI - Inhibition of tumor necrosis factor by curcumin, a phytochemical. AB - Curcumin, contained in the rhizome of the plant Curcuma longa Linn, is a naturally occurring phytochemical that has been used widely in India and Indonesia for the treatment of inflammation. The pleiotropic cytokine tumor necrosis factor-alpha (TNF) induces the production of interleukin-1 beta (IL-1), and, together, they play significant roles in many acute and chronic inflammatory diseases. They have been implicated in the pathogenesis of intracellular parasitic infections, atherosclerosis, AIDS and autoimmune disorders. This report shows that, in vitro, curcumin, at 5 microM, inhibited lipopolysaccharide (LPS) induced production of TNF and IL-1 by a human monocytic macrophage cell line, Mono Mac 6. In addition, it demonstrates that curcumin, at the corresponding concentration, inhibited LPS-induced activation of nuclear factor kappa B and reduced the biological activity of TNF in L929 fibroblast lytic assay. PMID- 7786296 TI - Sulphoxide reduction by rat and rabbit tissues in vitro. AB - The reduction of sulindac, sulphinpyrazone and diphenyl sulphoxide to their thioether analogues has been studied in vitro using rat and rabbit tissues. Sulindac reduction was about 10-fold higher in homogenates of rat kidney and liver than in other tissues although the tissue differences decreased when dithiothreitol was used as a co-factor. The greatest sulindac reducing activity in rat liver was in the cytosolic fraction whereas reoxidation of the thioether back to the sulphoxide was largely in the microsomal fraction. Studies using NADPH/NADH, acetaldehyde and dithiothreitol as cofactors showed that aldehyde oxidase was the main sulindac reducing system in rat and rabbit liver cytosols but not in renal cytosols where reduction was probably linked to the thioredoxin system, as reported previously. Menadione and hydralazine caused essentially complete inhibition of sulindac reduction by hepatic but not renal cytosol and the inhibition was dependent on preincubation of the enzyme with the inhibitor, which is indicative of aldehyde oxidase activity. Little reduction of sulphinpyrazone or diphenyl sulphoxide was detected with rat or rabbit kidney or renal cytosols, although increased reduction was detected when acetaldehyde was added as a cofactor to rabbit and rat liver cytosols. The data indicate that different enzyme systems are responsible for sulphoxide reduction in the liver and kidney. PMID- 7786297 TI - Sulphoxide reduction by rat intestinal flora and by Escherichia coli in vitro. AB - The caecal microflora from female rats show a greater ability to reduce the sulphoxide group of sulindac than either the liver or kidneys. Studies on sulphoxide reduction by Escherichia coli showed that NADH, NADPH and dithiothreitol (DTT), but not acetaldehyde could act as cofactors. The cytosolic fraction was responsible for about 90%, 80% and 60% of the total reducing activity with sulindac, diphenyl sulphoxide and sulphinpyrazone, respectively. The main NADPH linked activity in the E. coli cytosol was dependent on thioredoxin, since the activity was essentially abolished by passing through a G50 column or by the addition of anti-thioredoxin anti-serum. Partial purification and separation of sulphoxide reducing activity by DEAE-cellulose chromatography separated two main protein bands, each of which possessed sulindac reducing activity. The importance of thioredoxin for much of the NADPH dependent activity was confirmed but the eluate fractions also showed the presence of other activities with NADH, NADPH and DTT that were independent of thioredoxin. Incubation of the DEAE-cellulose eluate fractions with flosequinan and sulphinpyrazone showed that the reducing activity in the two main protein peaks showed different substrate specificities and that there were multiple sulphoxide reductase systems present in E. coli cytosol. PMID- 7786298 TI - 1-O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine--a methoxy ether lipid inhibiting platelet activating factor-induced platelet aggregation and neutrophil oxidative metabolism. AB - Whether or not two alkylglycerols could initiate a functional response in human platelets or modify responses induced by platelet activating factor (PAF) was evaluated. It was found that 1-100 microM 1-O-hexadecyl-2-metoxy-glycero-3 phosphatidylcholine (Et-16-OCH3) induced platelet aggregation but 1-O-hexadecyl sn-glycerol (chimyl alcohol; CA) did not. Et-16-OCH3-induced platelet aggregation was abolished by pretreatment with the PAF receptor antagonist WEB 2086. While CA had no effect on platelet aggregation induced by PAF, pretreatment with Et-16 OCH3 (0.1 microM or higher) significantly inhibited platelet aggregation induced by PAF, but had no effect on aggregation caused by ADP, thrombin or phorbol myristate acetate (PMA). A receptor binding study using radiolabelled [3H]WEB 2086 showed that Et-16-OCH3 exerts its actions through interaction with the PAF receptor. Moreover, Et-16-OCH3 inhibited neutrophil chemiluminescence responses induced by PAF, but not reactions to PMA or a formyl peptide. Finally, 1 microM Et-16-OCH3 induced a rise in the intracellular calcium concentration in platelets equal to that induced by PAF and also had an calcium ionophore-like effect at 100 microM. Thus, this study shows that Et-16-OCH3 is both a potent inducer of platelet aggregation and an inhibitor of PAF-induced platelet aggregation and neutrophil chemiluminescence, through interaction with the PAF receptor. PMID- 7786299 TI - Effects of the phosphatase inhibitor calyculin A on the phosphorylation of C protein in mammalian ventricular cardiomyocytes. AB - The effects of inhibitors of protein phosphatase activity on C-protein phosphorylation were studied in preparations from mammalian ventricles. Calyculin A (CyA), an inhibitor of type 1 and 2A protein phosphatases, was studied. CyA concentration- and time-dependency increased the phosphorylation state of C protein in isolated 32P-labelled guinea pig ventricular cardiomyocytes. C-protein was identified by its reaction with a polyclonal antibody and immunoprecipitation. It is concluded that C-protein in intact cardiomyocytes could be a substrate for type 1 and 2A protein phosphatases. PMID- 7786300 TI - Formation of mono- and diglucuronides and other glycosides of benzo(a)pyrene-3,6 quinol by V79 cell-expressed human phenol UDP-glucuronosyltransferases of the UGT1 gene complex. AB - Glucuronidation of quinols of polycyclic aromatic hydrocarbons (PAHs) represents an important detoxication pathway preventing toxic quinone/quinol redox cycles. Therefore, mono- and diglucuronide formation of benzo(a)pyrene-3,6-quinol was investigated and compared to that of structurally related 3,6-dihydroxychrysene and simple phenols (1-naphthol and 4-methylumbelliferone) using V79 cell expressed human UGT1.6 (= P1) and human UGT1.7 (= P4). Properties of human UGT1.6 were compared to those of the rat ortholog. Cofactors related to UDP-glucuronic acid such as UDP-galacturonic acid and UDP-glucose were also studied. It was found that rat and human UGT1.6 and human UGT1.7 catalyse monoglucuronide formation of planar PAH quinols. Diglucuronide formation was only detectable with human UGT1.7. The UGT isozymes studied also formed galacturonides and, although only to a minor extent, glucosides. Rat UGT1.6 (but not the human ortholog) catalysed digalacturonide formation of benzo(a)pyrene-3,6-quinol; the in vivo significance of galacturonide formation remains to be established. The results suggest that planar PAH phenols and quinols are conjugated more efficiently by human UGT1.7 than by UGT1.6, which preferentially conjugates simple planar phenols. PMID- 7786301 TI - Modification of DNA bases by anthralin and related compounds. AB - Modification of bases in calf thymus DNA by treatment with the antipsoriatic drug anthralin was studied. The products of DNA bases were identified and their yields measured by gas chromatography-mass spectrometry with selected ion monitoring. Treatment of calf thymus DNA with anthralin significantly enhanced the amount of modified bases above control levels. Purine bases were modified to products identical with those known to be typical of DNA damage induced by hydroxyl radicals. The yields of Fapy-adenine, 8-hydroxyadenine, Fapy-guanine, and 8 hydroxyguanine were maximally increased at an anthralin concentration of 75 microM. A variety of structural analogues of anthralin were also tested at 75 microM were either weaker or stronger hydroxylating agents. It is likely that damage to DNA bases induced by anthrones contributes to their antiproliferative activity. The pharmacological implications of these characteristics of the action of anthralin on DNA bases are discussed. PMID- 7786302 TI - Photosensitized inhibition of growth factor-regulated protein kinases by hypericin. AB - The naphthodianthrone hypericin causes a photosensitized inhibition of protein kinases involved in growth factor signalling pathways. Nanomolar concentrations of hypericin inhibit the protein tyrosine kinase activities (PTK) of the epidermal growth factor receptor and the insulin receptor, while being ineffective towards the cytosolic protein tyrosine kinases Lyn, Fgr, TPK-IIB and CSK. Photosensitized inhibition by hypericin is not restricted to receptor-PTKs since the Ser/Thr protein kinases (protein kinase CK-2, protein kinase C and mitogen-activated kinase) are also extremely sensitive to inhibition (IC50 value for protein kinase CK-2 = 6 nM). A comparison of the hypericin-mediated inhibition of the epidermal growth factor-receptor PTK and protein kinase CK-2 revealed that the inhibition is irreversible, strictly dependent upon irradiation of the enzyme-inhibitor complex with fluorescent light and likely mediated by the formation of radical intermediates (type I mechanism). Although the exact molecular basis for the selectivity of enzyme inhibition by hypericin remains unknown, our results suggest that distantly related protein kinases could still share common reactive domains for the interaction with hypericin. PMID- 7786303 TI - Antinociceptive activity of calcitonin and central cholinergic system: behavioural and neurochemical analyses. AB - Behavioural and neurochemical analyses were carried out to investigate the relationship between the antinociceptive activity of porcine calcitonin (pCT) and central cholinergic system in mice and rats. Behavioural studies revealed that the antinociceptive activity of pCT encapsulated in sulphatide-containing liposomes injected intravenously into mice was significantly inhibited by atropine sulphate, but not by atropine methylnitrate, and potentiated by physostigmine, but not by neostigmine. Neurochemical studies using rat brain synaptosomes showed that pCT stimulated synaptosomal sodium-dependent high affinity choline uptake, which was found to be closely associated with acetylcholine (ACh) synthesis (50-60%). This effect was concentration-dependent. In addition, pCT elicited a biphasic effect on ACh release from synaptosomes with an initial brief period of stimulation and subsequent prolonged inhibition. This stimulation was not affected by atropine sulphate, but markedly reduced by incubation in the presence of diltiazem or in a calcium-free medium, indicating that the modulation of ACh release by the peptide may be mediated by calcium fluxes across the synaptosomal membrane independent of cholinergic receptor activation. However, pCT does not affect the activity of synaptosomal acetylcholinesterase. Therefore, the behavioural study in vivo with the neurochemical analysis in vitro suggests that the central cholinergic system may be involved in the antinociceptive activity of calcitonin. PMID- 7786305 TI - Virtual cofactors for an Escherichia coli nitroreductase enzyme: relevance to reductively activated prodrugs in antibody directed enzyme prodrug therapy (ADEPT). AB - A nitroreductase enzyme has been isolated from Escherichia coli that has the unusual property of being equally capable of using either NADH or NADPH as a cofactor for the reduction of its substrates which include menadione as well as 5 (aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954). This property is shared with the mammalian enzyme, DT diaphorase. The nitroreductase can, like DT diaphorase, also use simple reduced pyridinium compounds as virtual cofactors. The intact NAD(P)H molecule is not required and the simplest quaternary (and therefore reducible) derivative of nicotinamide, 1-methylnicotinamide (reduced), is as effective as NAD(P)H in its ability to act as an electron donor for the nitroreductase. The structure-activity relationship is not identical to that of DT diaphorase and nicotinic acid riboside (reduced) is selective, being active only for the nitroreductase. Irrespective of the virtual cofactor used, the nitroreductase formed the same reduction products of CB 1954 (the 2- and 4-hydroxylamino derivatives in equal proportions). Nicotinic acid riboside (reduced), unlike NADH, was stable to metabolism by serum enzymes and had a plasma half-life of seven minutes in the mouse after an i.v. bolus administration. NADH had an unmeasurably short half-life. Nicotinic acid riboside (reduced) could also be produced in vivo by administration of nicotinic acid 5'-O-benzoyl riboside (reduced). These results demonstrate that the requirement for a cofactor need not be a limitation in the use of reductive enzymes in antibody directed enzyme prodrug therapy (ADEPT). It is proposed that the E. coli nitroreductase would be a suitable enzyme for ADEPT in combination with CB 1954 and a synthetic, enzyme selective, virtual cofactor such as nicotinic acid riboside (reduced). PMID- 7786304 TI - Adenylyl cyclase in SH-SY5Y human neuroblastoma cells is regulated by intra- and extracellular calcium. AB - Adenylyl cyclase exists as a family of closely related subtypes which differ in their tissue distribution and regulatory properties. Submicromolar rises in [Ca2+]i produced via activation of phospholipase C (PLC) or Ca2+ channel opening, provide a mechanism by which Ca2+/calmodulin (CaM) or protein kinase C (PKC) sensitive isoforms of adenylyl cyclase can be regulated. In this study we have examined, in detail, the muscarinic (M3) regulation of adenylyl cyclase in SH SY5Y cells and report a role for both [Ca2+]e and [Ca2+]i. Carbachol (1 mM) and potassium (100 mM) caused a time (T1/2 = 3 and 4 min, respectively) and dose (EC50 = 6.95 microM and 34.7 mM respectively) related increase in cAMP formation. This amounted to an approximate two-fold increase over basal levels. Carbachol and potassium also caused a biphasic increase in [Ca2+]i with basal, peak and plateau values of 118.4 nM, 697.6 nM, 253.0 nM and 104.0 nM, 351.6 nM, 181.5 nM, respectively. Calcium channel blockade with nickel (2.5 mM) abolished potassium stimulated cAMP formation and rises in [Ca2+]i. However, carbachol-stimulated cAMP formation was significantly decreased only at the later time points, where rises in [Ca2+]i were also essentially abolished. Further evidence for a role for [Ca2+]e and [Ca2+]i is provided by the stimulation of cAMP formation by carbachol in the absence of added Ca2+, followed by a further increase on its re-addition. Carbachol- and potassium-stimulated cAMP formation were inhibited by the CaM antagonist trifluoperazine (100 microM). The mu-opiate agonists, morphine and fentanyl also inhibited carbachol-stimulated cAMP formation. In addition, cAMP formation in SH-SY5Y cell membranes was significantly increased in the presence of Ca2+ (1.46 microM), CaM (200 nM) and forskolin (1 microM). PKC inhibition with Ro 31 8220 did not affect carbachol-stimulated cAMP formation. Taken collectively, these data suggest that SH-SY5Y cells express type 1, and possibly type 8 isoforms of adenylyl cyclase, which can be regulated by intra- and extracellular Ca2+. PMID- 7786306 TI - Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761. AB - Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2 amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis parinaric acid with peroxyl radicals generated from 2,2'-azobis (2,4 dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha-tocopherol and beta carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761. PMID- 7786307 TI - Characterization of the independent and combined effects of two inhibitors on oxidative drug metabolism in rat liver microsomes. AB - To evaluate how two inhibitors influence oxidative drug metabolism, this study investigated the inhibitory effects of mexiletine with cimetidine and mexiletine with lidocaine, both individually and in combination, on the oxidative metabolism of two probe substrates, aminopyrine and aniline in rat liver microsomes. Mexiletine was a competitive inhibitor of aminopyrine N-demethylation, whereas cimetidine was a mixed type of inhibitor (Ki = 2.00 +/- 0.04 and 0.20 +/- 0.02 mM, respectively). For aniline hydroxylation, mexiletine exhibited a mixed type of inhibition, whereas lidocaine was a noncompetitive inhibitor (Ki = 0.60 +/- 0.07 and 8.50 +/- 0.12 mM, respectively). The combined inhibition of either mexiletine with cimetidine or mexiletine with lidocaine on aminopyrine and aniline metabolism was close to the fully additive effects of the individual compounds when their individual concentrations were below a 2-fold Ki concentration, regardless of the apparent kinetic inhibition type. The combined inhibition was less than fully additive when the individual concentrations were twice the Ki or above. These results demonstrate that, when two inhibitors of oxidative drug metabolism are combined, both the Ki values and the concentrations of inhibitors play important roles in determining the extent of additive inhibition of enzyme activity. PMID- 7786308 TI - Rapid changes in cytochrome P4502E1 (CYP2E1) activity and other P450 isozymes following ethanol withdrawal in rats. AB - This study describes the effects of chronic ethanol (ETOH) treatment and withdrawal on the rat hepatic mixed-function mono-oxygenase system. Male Sprague Dawley rats (150-200 g, 10 per group) were administered ETOH as part of the Lieber-deCarli liquid diet for 3 weeks. Ethanol was removed, and the animals were euthanized at 0, 24, 48, 72 and 168 hr post-withdrawal. Microsomes were prepared, and ethanol-inducible cytochrome P4502E1 (CYP2E1) activity was measured using the enzyme markers N-nitrosodimethylamine demethylase (NDMAd), p-nitrophenol hydroxylase (PNPH) and aniline hydroxylase (AH). Activities were found to be induced significantly after chronic ETOH feeding using all three assays (NDMAd, 5 fold; PNPH, 3.5-fold; AH, 9-fold). Upon ETOH withdrawal, all three activities dropped markedly, with NDMAd and PNPH at control values at 24 hr and all subsequent time points. AH activity remained 3-fold higher than controls at 24, 48 and 72 hr. Western blot analyses showed that immunoreactive CYP2E1 returned to control at 24 hr, consonant with NDMAd and PNPH activities. The prolonged induction of AH activity following ETOH withdrawal indicates that it is not a specific marker of CYP2E1-catalyzed reactions. Collectively, these data are suggestive of a rapid mechanism of CYP2E1 degradation in the rat liver. Of the other parameters investigated in this study, total cytochrome P450 content was increased 2.5-fold after ETOH feeding, with levels dropping markedly 24 hr post withdrawal. NADPH-dependent cytochrome c reductase activity was unchanged throughout the course of the study. CYP1A1, CYP2B1 and CYP3A activities were assessed by the substrate probes ethoxyresorufin O-dealkylase (EROD), pentoxyresorufin O-dealkylase (PROD) and erythromycin N-demethylase (ERNd). EROD and PROD were induced significantly by ETOH administration (2-fold) at 0 hr, with EROD remaining elevated over controls 24 hr post-withdrawal. Quantitative western blot analysis of CYP1A1 and CYP2B1 revealed a pattern of immunostaining generally consistent with but less variable than levels predicted by the respective substrate markers. Both proteins were induced significantly by chronic ethanol administration (CYP1A1, 1.9-fold; CYP2B1, 4-fold). Induction of these P450 isoforms persisted for several days following withdrawal. In contrast, immunoreactive CYP1A2 was found to decrease significantly (by 30-40%) during ethanol withdrawal (24, 48, 72, 168 hr). ERNd activity was induced significantly by chronic ETOH feeding (2.5-fold) and remained so for 24 hr into the withdrawal period (2-fold). Immunoreactive CYP3A1 was also induced significantly following ETOH administration (0 hr) and 24 hr following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7786309 TI - Blockade of human neutrophil activation by 2-[2-propyl-3-[3-[2-ethyl-4-(4 fluorophenyl)-5- hydroxyphenoxy]propoxy]phenoxy]benzoic acid (LY293111), a novel leukotriene B4 receptor antagonist. AB - Leukotriene B4 (LTB4), a naturally occurring pro-inflammatory product of arachidonic acid metabolism, has been associated with human inflammatory disease. This study compares the abilities of two LTB4 receptor antagonists, 2-[2-propyl-3 [3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid (LY293111) and 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]- 3,4-dihydro-8 propyl-2H-1-benzopyran-2-carboxylic acid (SC-41930), to displace LTB4 binding and their functional blockade of human neutrophil activation. LY293111 inhibited the binding of [3H]LTB4 with a Ki of 25 nM; SC-41930 displayed a similar potency (Ki = 17 nM). In contrast, LY293111 prevented LTB4-induced calcium mobilization with an IC50 = 20 nM, or 40 times more effectively than SC-41930 (IC50 = 808 nM). LY293111 was 300 times more potent than SC-41930 in blocking LTB4-induced CD11b up-regulation on isolated neutrophils. LY293111 also arrested LTB4-induced up regulation of CD11b on neutrophils in whole human blood. LY293111 was not effective in blocking human neutrophil activation responses induced by N-formyl methionyl-leucyl-phenylalanine (fMLP), platelet-activating factor (PAF), human recombinant endothelial interleukin-8 (IL-8) or human recombinant complement component 5a (C5a). PMID- 7786310 TI - Identification of glutathione S-transferase as a determinant of 4 hydroperoxycyclophosphamide resistance in human breast cancer cells. AB - Aldehyde dehydrogenase (ALDH) is well known for its involvement in the resistance of tumor cells to cyclophosphamide (CPA) and its activated derivatives, such as 4 hydroperoxy-CPA (4HC). The role of other drug-metabolizing enzymes such as glutathione S-transferase (GST) in CPA resistance is, however, less certain. In the present study of a human breast cancer cell line (MCF-7) exhibiting about 6 fold resistance to 4HC (MCF/HC), cellular levels of glutathione (GSH) were increased 1.4-fold, while cytosolic GST and ALDH activities were increased 2.7- and 7.2-fold, respectively, relative to the MCF-7 parental line. No significant changes in glutathione peroxidase and NADPH cytochrome P450 reductase activity, and no increase in microsomal GST and GST pi mRNAs were found in the resistant cells. Treatment with the ALDH substrate octanal sensitized the cells to the cytotoxic effects of 4HC to a modest extent in both MCF-7 and MCF/HC cells [dose modification factor (DMF) of 1.4 and 1.6, respectively]. Depletion of GSH by treatment with the GSH synthesis inhibitor buthionine sulfoximine (BSO) enhanced the cytotoxic effect of 4HC to a similar extent in both cell lines. By contrast, ethacrynic acid, which inhibited GST activity by > 85% in MCF-7 and MCF/HC cell extracts without depletion of GSH, sensitized the resistant but not the parental cells to 4HC cytotoxicity, indicating the importance of GST as a determinant of 4HC resistance in these cells. This conclusion is supported by the observation that in MCF/HC cells, ethacrynic acid in combination with BSO increased the DMF 3 fold higher than did BSO or EA alone, while in the parental MCF-7 cells ethacrynic acid with BSO had no significant chemosensitization effect over BSO alone. These studies establish that in addition to ALDH, GST overexpression can contribute to acquired resistance of tumor cells to 4HC and, furthermore, suggest that modulators that target the GSH/GST system could be useful in overcoming CPA resistance in the clinic. PMID- 7786312 TI - Thermodynamic studies with acetylthiocholine on nicotinic receptors of mammalian skeletal muscle in vitro. AB - The temperature dependency of binding of acetylthiocholine, a specific nicotinic agonist, to the nicotinic receptor of mammalian skeletal muscle was studied using isotonic contractions of the rat denervated diaphragm preparation in vitro. The dissociation constants at different temperatures (22-39 degrees) were determined by the Furchgott method using alpha-bungarotoxin as an irreversible antagonist. Both free energy of association (delta G zero = -22.93 kJ/mol at 37 degrees) and enthalpy of binding (delta H zero = -58.35 kJ/mol) calculated from Kd (dissociation constant) and slope of lnKd versus 1/T (van't Hoff plot) respectively were found to be negative. The negative entropy value (delta S zero = -0.113 kJ/mol/deg) obtained from the intercept of this van't Hoff plot differs from the large positive value obtained earlier employing radioligand binding studies of the nicotinic receptor of Electrophorus electricus. PMID- 7786311 TI - Effect of eugenol on drug-metabolizing enzymes of carbon tetrachloride intoxicated rat liver. AB - The chemoprotection extended by eugenol against carbon tetrachloride (CCl4) intoxication was established by studies on drug-metabolizing phase I and phase II enzymes. An overall decrease in drug-metabolizing enzymes, namely NADPH cytochrome c reductase, NADH-cytochrome reductase, coumarin hydroxylase, 7-ethoxy coumarin-O-deethylase, UDP-glucuronyltransferase and glutathione-S-transferase, was observed with CCl4 intoxication, with a subsequent decrease in cytochrome P450 and cytochrome b5 content. CCl4 caused a significant decrease in microsomal phospholipids and the marker enzymes glucose-6-phosphatase and 5'-nucleotidase, and an increase in thiobarbituric acid reactive substances (TBARS). Simultaneous administration of eugenol with CCl4 inhibited the accumulation of TBARS and the decrease in the microsomal phospholipids and marker enzymes. Further, the chemical onslaught imposed by CCl4 on the drug-metabolizing system was removed successfully by eugenol. Eugenol appears to act as an in vivo antioxidant and as a better inducer of phase II enzymes than phase I enzymes. It is therefore suggested that eugenol could be an interesting basic structure for drug design. PMID- 7786313 TI - (-)-R-fenoprofen: formation of fenoprofenyl-coenzyme A by rat liver microsomes. AB - The thioesterification of fenoprofen (FPF) by rat liver microsomes has been studied using an HPLC method enabling direct quantification of the FPF-CoA produced. Over the concentration range studied (5-400 microM), studies showed the participation of a single CoA ligase in the formation of FPF-CoA, in contrast with the involvement of several isozymes with different affinities, that has been found with ibuprofen (IPF). The Km for the reaction was dependent upon the presence of non-ionic detergent, a concentration of 0.05% Triton X-100 reducing the Km from 397 to 20 microM although the detergent had no effect on Vmax. The microsomal long-chain fatty acid CoA ligase was markedly enantioselective towards (-)-R-FPF and the formation of (-)-R-FP-CoA was inhibited by both the (+)-S enantiomer and palmitic acid. PMID- 7786314 TI - [A new differentiation factor from culture media of the HL-60 cell line treated with retinoic acid. Isolation and primary structure determination]. AB - A new 8.2-kDa protein factor was isolated from cell culture of a promyelocyte leukemic HL-60 cell line that exhibited a differentiation-inducing effect upon the initial cell line. The primary structure of this factor was determined by sequencing the protein (N-terminal region) and the corresponding cDNA. A molecule of the differentiation factor secreted by HL-60 cells consisted of 54 amino acid residues and was glycosylated. PMID- 7786316 TI - [Polyacrolein latex as a solid phase carrier for radioimmunoassay. Comparison with microcrystalline cellulose and polystyrene test tube surface]. AB - The immunosorbent obtained through a covalent immobilization of antibodies on a polyacrolein latex was studied in comparison with the sorbents based on microcrystalline cellulose and with the surface of polystyrene test tubes in a two-center radioimmunoassay for ferritin. It was shown that the polyacrolein latex provides a covalent binding of up to 75 mg protein per g dry polymer with an immobilization efficiency of 50-70% and a high effective association constant of immobilized antibodies (Ka = 4.5 x 10(9) M-1). The same parameters for the sorbent based on microcrystalline cellulose were 33 mg/g, 25-35%, and 4.3 x 10(8) M-1, respectively. In the radioimmunoassay for ferritin, the immunosorbents based on polyacrolein latex and cellulose ensured a nearly the same analytical sensitivity at the level of (0.7-0.9) x 10(-13) M ferritin and pointed to the possibility of eliminating the "hook-effect". Compared to the immunosorbent based on polystyrene test tubes, the advantages of the polyacrolein latex are the decrease in the minimum detectable concentration (increase in analytical sensitivity), the extension of the dynamical range of analysis, and the absence of the "hook-effect". PMID- 7786315 TI - [Isolation and properties of carboxypeptidase from the Kamchatka crab Paralithodes camtshatica]. AB - Homogeneous carboxypeptidase PC from a hematopancreas of kamchatka crab Paralithodes camtshatica was obtained by means of an affinity chromatography on sorbents containing arginine, protamine hydrolysate, and phenylalanine as ligands with an yield 23% and purification degree 37.4. The isolated enzyme has a molecular mass 34 kDa, as evidenced by an SDS-PAGE; pI 3.1; an optimum pH 6.5, as estimated for hydrolysis of Dnp-Ala-Ala-Arg; pH-stability range 5-8 in the presence of Ca2+; a temperature optimum 55 degrees C; and Km 0.4 mM. The carboxypeptidase is activated by Co2+ and Ca2+ ions and is inhibited by EDTA and o-phenanthroline, and therefore, it is a metallocarboxypeptidase. The enzyme can effectively split off C-terminal residues Phe and Tyr, as well as Arg and Lys. Residues Pro, Glu, and Asp cannot be split off, and they stop the cleaving of a preceding bond. Thus, the carboxypeptidase PC of kamchatka crab has a mixed substrate specificity, which is characteristic of carboxypeptidase from crawfish and of microbial carboxypeptidases T and SG. The new carboxypeptidase has an amino acid composition Asp41Thr24Ser22Glu32Pro15Gly32Ala291/2Cys5Val19Met8Ile14Leu20Ty r18Phe8Lys7His4 Arg8Trp4. The N-terminal sequence of the enzyme demonstrate a 40% homology with the N-terminal sequence of carboxypeptidase from crawfish. PMID- 7786317 TI - [Polypeptides from murine peritoneal macrophages recognizing glycosaminylmuramoyl dipeptide]. AB - By means of radioligand analysis, murine peritoneal macrophages were shown to express several hundreds cell surface high-affinity GMDP-binding sites with a binding constant 350 pM. Photoaffinity labeling followed by SDS-PAGE enabled us to identify inside these cells 32-34 and 38 kDa proteins, specifically binding GMDP. Proteins 32-34 kDa were also detected by Western blotting analysis using biotinylated conjugate of polyacrylamide with immobilized GMDP-Lys [(GMDP-Lys) PAA-(Bi)] in cell lysate of murine peritoneal macrophages. PMID- 7786318 TI - [Synthesis of a cyclic enkephalin analog with prolonged action]. AB - A cyclic analog of enkephalin, cyclo(Lys-Tyr-DMet-Gly-Phe-Pro-) and two corresponding linear hexapeptides with lysine residue on the N- and C-termini of the pentapeptide sequence, Lys-Tyr-DMet-Gly-Phe-Pro and Tyr-DMet-Gly-Phe-Pro-Lys were synthesized by classical and solid phase methods of peptide chemistry. The cyclic analog exhibited significantly prolonged analgesic effect, evaluated by the "tail pinch" method after intracysternal injection to mice. The cycloanalog also had a weak influence on the peripheral opiate receptors of the isolated segment of guinea pig iliac intestine. Addition of the lysine residue to the N terminus of the pentapeptide sequence enhanced by an order of magnitude the selectivity of binding of the analog with opiate receptors of mu-type. PMID- 7786319 TI - [Dependence of the level of gene expression in E. coli on the structure of the translation initiation segment (TIR)]. AB - The expression levels of genes that are transcribed to give mRNAs with identical leader sequences and even with identical extended coding regions may differ considerably. In order to determine the mechanism of this phenomenon, secondary structures of some mRNAs synthesized from a series of expression plasmids were studied. It was shown that the effect of the mRNA secondary structure in the translation initiation region on the initiation efficiency is due not only to the hairpin formation in this region but also to long-range interactions. When complementary structures tighter than those resulted from the interaction of regions SD, UB1, UB2, and DB with 16S rRNA are formed, the efficiency of the translation initiation and, consequently, the expression level decrease. PMID- 7786320 TI - [Modification of pyrimidine nucleosides using nicotinic acid derivatives]. AB - Interaction of nicotinoyl chloride in situ with 2'-deoxyuridine, its 3'-O-acetyl , or 5'-O-trityl derivatives led to 3'-O-nicotinoyl-, 5'-O-nicotinoyl-, 3',5'-di O-nicotinoyl-, and N3,3'-di-O-nicotinoyl-2'-deoxyuridine. Similarly, 5'-O nicotinoyl-6-azauridine resulted from the reaction of 2',3'-O-ethoxymethylidene-6 azauridine followed by the deprotection. Reaction of 5'-amino-5'-deoxy-2',3'-O ethoxymethylidene-6-azauridine with nicotinic acid in the presence of 2-ethoxy-1 ethoxycarbonyl-1,2-dihydroquinoline followed by the cleavage of the 2',3'-O protecting group gave 5'-deoxy-5'-nicotinamido-6-azauridine. The same compound was obtained from 5'-amino-5'-deoxy-6-azauridine and N-succinimidyl nicotinate. Structures of the compounds obtained were corroborated by 1H NMR spectra. It is shown that 3',5'-di-O-nicotinoyl-2'- deoxyuridine and 5'-deoxy-5'-O-nicotinamido 6-azauridine are cytotoxic toward CaOv cells in vitro (CE50 10(-5) M). PMID- 7786321 TI - [Nonchemical methods of modifying substrates for studying biopolymers with atomic force microscopy]. AB - Two simple procedures of DNA molecule fixation on mica for following imaging by the atomic force microscopy were developed. The distinctive features of the procedures are their simplicity, absence of chemical modification stages, and the possibility to obtain the images in air under relative high humidity. Comparison of the features of the images obtained indicated that the procedures developed were competitive with the procedures earlier suggested. PMID- 7786322 TI - [Open access upper endoscopy. Can the practice be improved?]. AB - 150 patients who were referred to the open access endoscopical unit in a county hospital for upper gastrointestinal examination were evaluated. The aim was to answer the following questions: How often is this upper GI-endoscopy of value for medical treatment of the patient, and is "open access endoscopy" a practical system? In order to obtain a more reliable diagnosis it is necessary to examine the patient without delay, and thereby avoid the masking effect of H-2 blockers and omeprazole. More attention to anamnestic risk factors would improve case selection. In many cases it is possible to rely on X-ray examination, and thus reduce the burden on the endoscopy unit and allow for instant endoscopy service. PMID- 7786323 TI - [Meta-analyses are necessary but technically difficult. Hard criticism against an article on mammography]. PMID- 7786324 TI - Chromosome mapping and organization of the human beta-galactoside alpha 2,6 sialyltransferase gene. Differential and cell-type specific usage of upstream exon sequences in B-lymphoblastoid cells. AB - The human beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1) (SiaT-1) gene is localized to human chromosome 3 (q21-q28) by Southern analysis of somatic cell hybrids and by in situ hybridization of metaphase chromosomes. Comparative analysis between the human and the previously reported rat SiaT-1 genomic sequences demonstrates precise conservation of the intron/exon boundaries throughout the coding domains. Furthermore, there is extensive inter-species sequence similarity in some of the exons that contain information only for the 5' leader regions. Human genomic sequences were also analyzed to reconcile reported differences in the 5'-untranslated region in SiaT-1 mRNAs. In cultured cell lines of the B-lineage, Reh, Nalm-6, Jok-1, Ball-1, Daudi, and Louckes, the study demonstrates that three upstream exons, Exons(Y+Z) and Exon(X), are mutually exclusively utilized, resulting in at least two distinct populations of SiaT-1 mRNA being synthesized. None of these exons is present in the SiaT-1 mRNA isotype expressed in HepG2 human hepatoma cells. In all B-lymphoblastoid cell lines examined, the basal level SiaT-1 mRNA is maintained by the expression of an isotype containing the Exons(Y+Z) sequence. The slightly smaller SiaT-1 mRNA, which contains the Exon(X) sequence but not Exons(Y+Z) sequence, is synthesized at a high level and found only in Jok-1, Daudi, and Louckes, the cell lines with mature B-cell phenotype. The study also provides further evidence that induced SiaT-1 expression accompanies the appearance of CDw75, a putatively sialylated cell surface epitope and a marker of human mature B-lymphocytes. The SiaT-1 induction is the result of the appearance of a novel form of SiaT-1 mRNA isotype. PMID- 7786325 TI - [Smoking and fetal growth. Do nicotine levels in tobacco play a role?]. PMID- 7786328 TI - [Alternative cancer treatment and informative censorship]. PMID- 7786327 TI - [Gonadal functional disorders following the therapy of testicular tumors]. PMID- 7786326 TI - [Consensus diagnosis pulmonary embolism]. PMID- 7786329 TI - [Oral typhoid vaccination and cross immunity against enteritis-causing salmonellae]. PMID- 7786330 TI - [Open access upper endoscopy. Selection of upper endoscopy]. PMID- 7786331 TI - [More on normal fees]. PMID- 7786333 TI - [Abuse potential during use and withdrawal psychosis after treatment with the hypnotic zolpidem (Stilnoct)]. AB - Three cases are presented. Withdrawal symptoms and ultimately psychosis developed in two cases following cessation of the hypno-sedative zolpidem. Two cases involve dependence upon and abuse of the drug; in one, a well-known alcoholic, it was abused in combination with alcohol, the other had prior well-known dependence on sedative hypnotics. One patient had chronic dysphoria and one encephalopatia toxica. Adverse effects such as withdrawal symptoms, dependence and abuse have not previously been reported in relation to zolpidem. Chemically unrelated to benzodiazepines, zolpidem is thought to have fewer adverse effects, but shares a pharmacokinetic profile with the benzodiazepine triazolam. It is advised that normal criteria for the prescription of benzodiazepines also be used when prescribing non-benzodiazepine sedatives and hypnotics, as they act upon the same receptor, namely the benzodiazepine-GABA-chloride complex. PMID- 7786332 TI - Folate status, women's health, pregnancy outcome, and cancer. AB - Key observations by Dr. Lucy Wills 65 years ago have led to the identification of folate as a nutrient essential for the prevention of megaloblastic anemia of pregnancy. The more recently discovered relationships of folate status to cervical dysplasia, neural tube defects, and atherosclerosis are reviewed here. PMID- 7786334 TI - [Treatment possibilities in basal cell carcinoma]. PMID- 7786335 TI - [Trained personnel is needed for home care of patients with mental disorders]. PMID- 7786336 TI - [Guidelines for advanced cardiopulmonary resuscitation of adults]. PMID- 7786337 TI - [Evaluation shows that centralization of thoracoscopic surgery is unnecessary]. PMID- 7786338 TI - [Treatment of ischemic heart disease--coronary surgery or angioplasty?]. PMID- 7786339 TI - [Molecular biology and physiology go hand in hand]. PMID- 7786340 TI - [Anaphylactic reactions following insect bites: clinical aspects, course and treatment]. PMID- 7786341 TI - Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus. AB - Tetanus and botulinum neurotoxins bind to nerve cells, penetrate the cytosol, and block neurotransmitter release. Comparison of their amino-acid sequences shows the presence of the highly conserved His-Glu-x-x-His zinc-binding motif of zinc endopeptidases (HExxH). Atomic absorption measurements of clostridial neurotoxins show the presence of one atom of zinc/toxin molecule bound to the light chain. The toxin-bound zinc ion is essential for the neurotoxins inhibition of neurotransmitter release in Aplysia neurons injected with the toxins. Phosphoramidon, a very specific inhibitor of zinc-endopeptidases, blocks the intracellular activity of the clostridial neurotoxins. Highly purified preparations of the light chain of tetanus and botulinum B and F neurotoxins cleaved specifically VAMP/synaptobrevin, an integral membrane protein of small synaptic vesicles, both in vivo and in vitro. From these studies, it can be concluded that the clostridial neurotoxins responsible for tetanus and botulism block neuroexocytosis via the proteolytic cleavage of specific components of the neuroexocytotic machinery. PMID- 7786342 TI - [Allopurinol]. PMID- 7786343 TI - [Personal development and continuing formation. A requirement for maintenance and improvement of the professional qualifications of nurses]. PMID- 7786344 TI - [Pain in children]. PMID- 7786345 TI - [Anti-inflammatory effects of cromones in asthma]. AB - The cromone family comprises sodium cromoglycate and the more recently developed nedocromil sodium. Nedocromil sodium prevents the bronchial obstruction induced by a variety of stimuli, including antigen. When given before antigen inhalation, nedocromil sodium prevents the early and late reaction and the increase in bronchial hyperresponsiveness. It is still effective in preventing the late phase when given after antigen exposure. These effects may result from the action of nedocromil sodium on inflammatory cells observed in vitro, particularly mast cells and eosinophils. When inhaled regularly, nedocromil sodium improves symptoms, especially in moderate asthma, decreases bronchial obstruction and reduces bronchial hyperreactivity. Bronchial biopsy studies have shown a decrease in activated eosinophils during prolonged nedocromil sodium treatment, suggesting that the clinical benefit results from an antiinflammatory effect of the drug. More recently, it has been suggested that nedocromil sodium may act on membrane chloride channel involved in activation of many cell types. In vitro data have shown a decrease in IgE production by isolated mononuclear cells, suggesting new therapeutic potential to be studied clinically. PMID- 7786346 TI - Antituberculous therapy and acute liver failure. PMID- 7786347 TI - Antituberculous therapy and acute liver function. PMID- 7786348 TI - Treadmill exercise training and estradiol differentially modulate hypothalamic pituitary-adrenal cortical responses to acute running and immobilization. AB - It is generally believed that physical fitness promotes health by attenuating responsiveness to other stressors. The experimental evidence for this belief is limited and does not extend to interactions between the hypothalamic-pituitary adrenal cortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We tested the hypothesis that treadmill exercise training would lead to an estrogen dependent hyporesponsiveness of the HPA axis that would generalize to immobilization stress. Ovariectomized female Sprague-Dawley rats (N = 74) that had been treadmill trained (TT) or sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of acute treadmill running or immobilization. Plasma (adrenocorticotrophin) (ACTH), (corticosterone) (B) and (prolactin) (PRL) were determined from trunk blood by radioimmunoassay and compared in a 2 group (TT vs. sedentary)-by-2 treatment (Eb vs. oil)-by-2 acute stressor (running vs. immobilization) design. Home-cage (HC) animals (N = 24) provided baseline hormone levels. ACTH and B levels were elevated after stressors in animals treated with either Eb or oil compared to HC, but increases in PRL after stressors were dependent on Eb. Treadmill exercise training led to an attenuation of ACTH and prolactin to running, but the attenuation did not generalize to immobilization. In contrast, treadmill exercise training led to a hyperresponsiveness of ACTH. Treadmill training did not modulate prolactin responses to immobilization. The modulating effects of the estradiol treatment are consistent with an interaction of the HPA and HPG axes in response to stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786349 TI - Carbohydrate, fat, and protein condition similar flavor preferences in rats using an oral-delay procedure. AB - Flavor preferences conditioned by carbohydrate (Polycose), protein (casein hydrolysate), and fat (corn oil) were compared using an oral-delay training method. In Experiment 1 separate groups of food deprived rats were trained to associate a CS+ flavor (e.g., grape-saccharin) with the delayed (10 min) presentation of isocaloric carbohydrate, protein, or fat sources. A CS- flavor (e.g., cherry-saccharin) was paired with the delayed presentation of an unflavored saccharin solution. In subsequent two-bottle tests the carbohydrate, protein, and fat trained groups displayed significant preferences for the CS+ over the CS-. In Experiment 2 each rat was trained to associate two new flavors with two of the three nutrients (e.g., orange with carbohydrate, and strawberry with protein). In subsequent two-bottle tests the rats equally preferred the two nutrient-paired flavors. Experiment 3 compared the preferences for the new CS+ flavors vs. the original CS-flavor. The rats displayed similar preferences for carbohydrate-, protein- and fat-paired CS+ over the CS-. The similar preferences obtained with the three different nutrients support the view that preference conditioning is mediated by the nutrients' caloric value. Other studies suggest, however, that nutrient-specific signals are also involved in the conditioning process. PMID- 7786350 TI - Anti-tuberculous therapy and acute liver failure. AB - The incidence of tuberculosis has been increasing since 1987, exposing a greater number of patients to the risks of three potentially hepatotoxic drugs, isoniazid, rifampicin, and pyrazinamide. Awareness of potentially severe drug hepatotoxic reactions is vital because fulminant hepatic failure is a devastating and often fatal condition without liver transplantation. We report four cases of fulminant hepatic failure caused by rifampicin, isoniazid, or both. These cases highlight the need for stricter adherence to and review of current guidelines on liver function tests after starting anti-tuberculous therapies. PMID- 7786351 TI - [Toward an integral vision of health reform]. PMID- 7786352 TI - Current results of lower extremity revascularization with vein grafts. PMID- 7786353 TI - Laser assisted surgery: the San Pablo experience. AB - Two thousand plus (2,000+) assisted laser surgical procedures were performed between July 1986 and November 1993. Multiwavelength specialties: Argon, CO2 and NdYAG usage include: general surgery, thoracic surgery, neurosurgery, ophthalmology, and gynecology. 65% of the patients were female whose ages range from 6 to 105 years. Endoscopic vs. handheld procedures ratios 1:1. In 95% of the cases attended, the procedures were performed for benign conditions. The office hospital usage distribution was 60-40%. The office morbidity was 0.8% (16 out of 2,000 cases) and a mortality of 0.15% (3 out of 2,000 cases). A reported 100% safety compliance was seen. Laser assisted surgery is a safe, effective and reliable option available to the surgeon's armamentarium. It appears that in some procedures it will allow shorter hospital stays and an earlier return of the patient to his/her normal routine. PMID- 7786354 TI - Changing trends in adenotonsillectomy at San Pablo Hospital 1983 vs. 1993. AB - The purpose of this paper is to review the changing trends in Adenotonsillectomies performed in San Pablo Medical Center during the last ten years. We have reviewed using a 25 variable questionnaire all patients undergoing this surgical procedure during the first six months in 1983 and compared the information with the patients having this procedure during the first six months of 1993. We conclude that the number of interventions, the indications, prior medical history and cost effects have changed substantially. Our data supports the accuracy of some of the trends being reported in the literature regarding this surgical intervention. PMID- 7786355 TI - Dengue fever with thrombocytopenia: studies towards defining vulnerability of bleeding. AB - PURPOSE: To define the period of greater vulnerability of bleeding in patients with Dengue fever in reference to the onset of their constitutional symptoms and the laboratory abnormalities. PATIENTS AND METHODS: In a retrospective study we reviewed the records of all patients admitted to San Pablo Medical Center in 1991 with a diagnosis of Dengue Fever or Hemorrhagic Dengue. All patients with a platelet count of less than 125,000 were included for analysis. The exclusion criteria included the presence of systemic disorders which may influence the platelet count, and patients without documentation regarding the presence of constitutional symptoms suggestive of viral illness. RESULTS: A total of 101 patients were analyzed of which only 74 were included in the study. All patients had fever and chills; skin rash, asthenia and general malaise was seen in over 50% of patients. Over 70% of patients had recovery of their platelet count, and most had their maximal thrombocytopenia within the 5th day and 8th day from the onset of constitutional symptoms. Leukopenia was seen in over 70% of patients with its lowest level within the 5th and 8th day from the onset of the constitutional symptoms. Significantly prolonged partial thromboplastin time was seen in 11% of the patients. Proteinuria was seen in 22% of the patients, 38% of which had it within the first 4 days of the onset of constitutional symptoms and also noted on the 5th and 6th day. Alteration in liver enzymes were noted in 47% of patients, with a maximal severity distributed in all time frames. Hypoalbuminemia was present in 28% of the patients, of these 67% presented within the first 4 days from the onset of constitutional symptoms. The pulse rate was usually normal in spite of the patient's dehydration and fever. CONCLUSIONS: We identified three phases that define the sequence of events seen in the majority of patients with Dengue Fever and Thrombocytopenia. These are: 1. proteinuria and hypoalbuminemia; 2. maximal cytopenia; 3. bradycardia and liver enzyme elevation. We believe this information is useful in the management of patients with Dengue Fever and thrombocytopenia. PMID- 7786356 TI - Group B streptococcal disease in pregnancy. AB - Group B Streptococcal (GBS) infection in the pregnant female represents a challenging and often complex scenario which may cause deleterious effects in the neonate. In this paper we present three case reports of GBS infection in neonates with different outcome. A comprehensive review of the history, microbiology, clinical presentation and therapy guidelines is presented. Early diagnosis and institution of therapy are the most important factors which may have an impact on maternal and neonatal outcome. PMID- 7786357 TI - [Risk management in the hospital industry]. AB - The author provides an introduction to the risk management process in the hospital industry as well as explains some of the basic elements in a risk management program in such industry. The author also explains the factors to be evaluated in a risk management program. PMID- 7786358 TI - Rehabilitation of the patient with an anterior cruciate ligament injury: a brief review. PMID- 7786359 TI - The pediatric inguinal hernia: is contralateral exploration justified? AB - To determine if contralateral inguinal hernia exploration is justified we decided to study our experience with 161 consecutive cases who underwent bilateral repair during a 30 months period. 61% of the population were infants younger than two years of age, and 19% premature babies. 69 pts presented with an RIH, 47 with an LIH and 45 pts with BIH. 16% suffered an episode of preoperative incarceration which were all reduced satisfactorily and operated promptly. A positive contralateral finding (either a hernial sac or a patent processus vaginalis) was identified in 74% RIH and 72% LIH patients upon exploration. No incidence of testicular edema/atrophy, vas deferens injury, or recurrence was reported in the six-year follow-up of the study. Statistical analysis of the contralateral findings during surgery with sex, gestational age and age at operation showed that females and infants younger than two months of age had a higher probability of having positive findings. We could not show that prematurity or left-sided hernias were associated with a higher positive contralateral rate. The major benefit of contralateral exploration is based on the fact that it allows discovery and elimination of a patent processus vaginalis so a hernia cannot develop subsequently. We conclude by establishing certain criteria that justifies the routine contralateral exploration of the pediatric hernia: the surgeon should be experienced in child care, associated conditions should not increase the surgical risks significantly, time-consuming dissections of the cord structures should be discouraged, and the operating time should be kept to a minimum. PMID- 7786360 TI - Other attitudes affecting the doctor-patient relationship. PMID- 7786361 TI - Who needs history? PMID- 7786362 TI - Proposal for a standardized electronic medical student record. PMID- 7786363 TI - Compliance with the review requirement for residency program sponsors. PMID- 7786364 TI - Training residents to work with diverse populations. PMID- 7786365 TI - CQI and planning the expansion of the primary care workforce. PMID- 7786366 TI - A reexamination of the NRMP matching algorithm. National Resident Matching Program. AB - Most graduating medical students in the United States find their first professional appointments through the National Resident Matching Program (NRMP). This service receives rank-order lists of preferences from students and from hospitals, and then generates final assignments of students to hospitals through the use of a specific computerized matching algorithm. The author uses recent findings from the mathematics and economics literatures to demonstrate three difficulties with the NRMP's matching algorithm and the official descriptions thereof. First, the algorithm favors hospitals over students, a feature known to the NRMP since at least 1976, but, in the author's opinion, not made clear in NRMP literature for students. Second, the author argues that the NRMP's justification that its algorithm mimics orderly, noncentralized admission processes is not correct. Institutions operating under non-centralized procedures must typically make more initial offers than there are positions, in the realization that some fraction of their offers will be declined. This arrangement enlarges the choices available to many applicants, and thereby benefits them, whereas the NRMP's algorithm unrealistically assumes that no institution would ever send out any extra offers. Third, the NRMP's algorithm contains incentives for students to misrepresent their true preferences when constructing their rank order lists. This feature is a substantial disadvantage of the current algorithm and is incorrectly described in literature distributed to students and in published articles from the NRMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786367 TI - The NRMP matching algorithm revisited: theory versus practice. National Resident Matching Program. AB - The authors examine the algorithm used by the National Resident Matching Program (NRMP) in its centralized matching of applicants to U.S. residency programs ("the Match"). Their goal is to evaluate the current NRMP matching algorithm to determine whether it still fulfills its intended purpose adequately and whether changes could be made that would improve the Match. They describe the basic NRMP algorithm and many of the variations of the matching process ("match variations") incorporated over the last 20 years to meet participants' requirements. An overview of the current state of the theory of preference matching is presented, including descriptions of the characteristics of stable matches in general, program-optimal and applicant-optimal matchings, and strategies for formulating preference lists. The characteristics of the current NRMP algorithm are then compared with the theoretical findings. Research conducted long after the original NRMP algorithm was devised has shown that an algorithm that produces stable matches is the best approach for matching applicants to positions. In the absence of requirements to satisfy match variations, the NRMP's deferred acceptance algorithm produces a program-optimal stable match. When match variations, such as those handled by the NRMP, must be introduced, it is possible that no stable matching exists, and the resulting matching produced by the NRMP algorithm may not be program-optimal. The question of program-optimal versus applicant-optimal matchings is discussed. Theoretical and empirical evidence currently available suggest that differences between these two kinds of matchings are likely to be small. However, further tests and research are needed to assess the real differences in the results produced by different stable matching algorithms that produce program-optimal or applicant-optimal stable matches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786368 TI - A model alcohol and other drug use curriculum for pediatric residents. AB - While alcohol and other drug (AOD) use is a major health risk for adolescents in the United States, there is a paucity of AOD training for pediatric residents. In 1991-92, the University of Wisconsin Medical School developed an experiential, community-based AOD curriculum for pediatrics residents. The curriculum included resident participation in a community-based AOD adolescent assessment and intervention program, interactive didactic sessions, role-playing practice, and interviewing skills sessions. The residents who participated in the curriculum (n = 25) were compared with a control group (n = 19). Evaluation included pre- and post-curriculum written tests, objective structured clinical examinations, and residents' ratings of the curriculum components. The residents who participated showed significant gains in AOD knowledge, utilization of screening techniques, and clinical management skills as compared with the controls. The residents gave positive ratings to all curriculum components. This well-received curriculum can serve as a national model both for AOD education in pediatrics and for curriculum development in other areas of adolescent health-risk-taking. PMID- 7786370 TI - Medicine's relation to homosexuality and for gay people within medicine. PMID- 7786369 TI - The potential of computerized representations of anatomy in the training of health care providers. AB - The purpose of anatomy education is to develop the skills for anatomical reasoning, which is a requirement for performing a number of clinical tasks. Anatomical reasoning integrates an understanding of the three-dimensional (3-D) geometry of the body and its parts (the spatial domain of anatomical information) with an understanding of functional, developmental, pathological, and other relationships among anatomic entities (the symbolic domain of anatomical information). Traditional methods in anatomy have substantial shortcomings for representing and integrating these two information domains. Computer-based methods of knowledge representation have a great potential for overcoming the shortcomings and for promoting anatomical reasoning. To realize this potential, there is a need for (1) establishing 3-D electronic atlases of the human body; (2) generating models of symbolic anatomical information, and (3) developing computer programs (user interfaces) that integrate these knowledge sources and serve the needs of trainees and practitioners in different fields of the health sciences. The Digital Anatomist Program at the University of Washington has begun to build such a client-server framework for anatomical information, and its application for biomedical education is being evaluated. PMID- 7786372 TI - Validity of three clinical performance assessments of internal medicine clerks. AB - PURPOSE: To analyze the construct validity of three methods to assess the clinical performances of internal medicine clerks. METHOD: A multitrait multimethod (MTMM) study was conducted at the Case Western Reserve University School of Medicine to determine the convergent and divergent validity of a clinical evaluation form (CEF) completed by faculty and residents, an objective structured clinical examination (OSCE), and the medicine subject test of the National Board of Medical Examiners. Three traits were involved in the analysis: clinical skills, knowledge, and personal characteristics. A correlation matrix was computed for 410 third-year students who completed the clerkship between August 1988 and July 1991. RESULTS: There was a significant (p < .01) convergence of the four correlations that assessed the same traits by using different methods. However, the four convergent correlations were of moderate magnitude (ranging from .29 to .47). Divergent validity was assessed by comparing the magnitudes of the convergence correlations with the magnitudes of correlations among unrelated assessments (i.e., different traits by different methods). Seven of nine possible coefficients were smaller than the convergent coefficients, suggesting evidence of divergent validity. A significant CEF method effect was identified. CONCLUSION: There was convergent validity and some evidence of divergent validity with a significant method effect. The findings were similar for correlations corrected for attenuation. Four conclusions were reached: (1) the reliability of the OSCE must be improved, (2) the CEF ratings must be redesigned to further discriminate among the specific traits assessed, (3) additional methods to assess personal characteristics must be instituted, and (4) several assessment methods should be used to evaluate individual student performances. PMID- 7786371 TI - Indicators of the educational effectiveness of subspecialty training programs in internal medicine. AB - PURPOSE: To identify markers within the subspecialty educational process in internal medicine that are associated with greater improvements in knowledge and skill. METHOD: Candidates for the 1991 cardiovascular disease examination of the American Board of Internal Medicine (ABIM) were matched to the fellowship programs they attended, and their performances on the internal medicine examination of the ABIM, demographic data, and performances on the cardiovascular disease examination were averaged within each program. Information on the programs themselves was also available. The variables were divided according to whether they controlled for input to the training programs, were indicators of educational process, or served as the outcome measure. Analyses were restricted to the 140 programs for which complete information was available and that had four or more candidates who took the cardiovascular examination (97 programs were excluded). RESULTS: The multiple correlation between all measures and scores on the cardiovascular disease examination was .80. Forty-five percent of the explained variance is attributable to previous performance on the internal medicine examination alone. The remaining 55% is shared by the educational indicators and the input measure or explained by the indicators alone. Among the indicators, location of medical school, length of fellowship training, ratings of overall clinical competence, fellow-to-faculty ratio, and number of subspecialties in the same institution made small contributions on their own. Program size, university affiliation, and period of approval by the residency review committee contributed little. CONCLUSION: The data are clear that indicators of educational process such as fellow-to-faculty ratio, longer periods of training, and performance during fellowship can generate greater gains in knowledge and judgment than would be expected if fellows merely built on their abilities at the time of entry to training. Such indicators may be useful if changes in health care delivery require reducing the numbers of specialty and subspecialty training positions. PMID- 7786373 TI - Analysis of the cost of training residents in a community health center. AB - BACKGROUND: Currently one federal program funds community health centers (CHCs) to provide services in underserved communities, and a second supports development of primary care teaching programs. Teaching CHCs respond to both program's goals, but their development is hindered by restrictive regulations of the two programs and lack of information regarding cost. METHOD: Spreadsheet software was used to develop a model that allocates cost components of a CHC-based residency. Productivity and staffing data from a teaching CHC program were used to estimate the cost of training and its sensitivity to selected variables. Data from 1992 through 1994 were collected from the family practice residency sponsored by the Brown University School of Medicine, the Memorial Hospital of Rhode Island, and the Blackstone Valley Community Health Center. RESULTS: An educational supplement of $13.21 per visit would be required for the program to be cost-neutral relative to staff. The cost of outpatient training for a resident averaged $13,935 per year. Residents would "break even" if they saw patients at 19% above the average rate recommended by the residency review committee. If staff physicians instead of residents had provided the patient care, the CHC would have saved $6,171 per resident. Additional savings from improved physician recruiting and decreased turnover would increase the value of the program to the CHC. Cost was most sensitive to resident productivity, precepting arrangements, nursing staff support, and staff turnover. CONCLUSION: Developing graduate medical education programs in CHCs can be a cost-effective way of increasing the pool of appropriately trained primary care physicians and increasing health care access for underserved populations. If teaching CHCs are to expand, provisions will need to be made for adequate reimbursement of their costs. PMID- 7786375 TI - A prospective, randomized trial of a six-week ambulatory medicine rotation. AB - BACKGROUND: Medical schools are placing increased emphasis on training students in the ambulatory setting, but few studies show the benefit or academic risk of such innovation. The authors studied the effect of such a new rotation with a rigorous study design. METHOD: From a group of 166 third-year students at the Uniformed Services University of the Health Sciences F. Edward Hebert School of Medicine assigned in 1990-91 to do six weeks of their third-year medicine clerkship at Walter Reed Army Medical Center, 106 volunteers were randomized to six weeks either on the usual rotation on the general medicine wards (69 students) or to a new ambulatory rotation (37 students). Multiple pre- and postclerkship parameters were used to evaluate clerkship skills and knowledge; eventual internship choice was determined. RESULTS: The randomization was successful. Postclerkship performances were the same in (1) the medicine subject examination of the National Board of Medical Examiners, (2) a multiple-choice test in interpreting laboratory results, (3) blinded rating by an expert panel of the quality of final written histories and physical exams, (4) blinded rating by an expert panel of the students' written case analyses of their own patients, and (5) a written multiple-step examination of problem-solving ability. Any differences between groups favored the ambulatory group. An increase in choice of primary care internships among students randomized to the ambulatory rotation was not significant. CONCLUSION: It is possible to study innovative rotations using a prospective, randomized design. Substituting a six-week block ambulatory experience for a ward rotation did not decrease students' abilities to write up or analyze complex cases. PMID- 7786374 TI - Influence of medical school applicants' demographic and cognitive characteristics on interviewers' ratings of noncognitive traits. AB - BACKGROUND: Interviews are commonly used to measure noncognitive traits of medical school applicants. The present study investigated the influence of knowledge of applicants' cognitive abilities on interviewers' ratings of noncognitive traits. METHOD: Academic and demographic predictors of interview ratings of applicants' noncognitive traits were examined at the Medical University of South Carolina College of Medicine during two years: 1992, when applicants' Medical College Admission Test (MCAT) total scores and undergraduate grade-point averages (GPAs) were available to interviewers; and 1993, when MCAT and GPA data were not available. In 1992, 226 applicants met study criteria (i.e., they received ratings from three interviewers in addition to having MCAT and GPA data on file); in 1993, 245 applicants met the criteria. Step-wise regression analyses were conducted to measure the influences of seven independent variables on applicants' interview ratings. Two-way analyses of variances and t tests were used to determine the effects of gender of applicants and interviewers. Cronbach's alpha coefficients were used as measures of interviewers' reliability. RESULTS: GPA was the best predictor for both years but accounted for double the amount of variance in interview ratings in 1992 (15.7%) compared with 1993 (7.4%). The reliability coefficients for the interviewers were .496 for 1992 and .473 for 1993. CONCLUSION: If the goal of the medical school admission interview is to assess noncognitive traits independently from academic skills, the authors recommend that MCAT and GPA data not be available to interviewers during interviews. The authors also found that gender and race influenced interview ratings in accordance with affirmative-action goals. Finally, the authors found that interview scores were only moderately reliable across different interviewers. They discuss ways to increase their reliability. PMID- 7786376 TI - Inpatient versus outpatient settings: where are the essential medical problems seen? PMID- 7786379 TI - Results of the National Resident Matching Program for 1995. PMID- 7786378 TI - Effect on medical education of computerized physician order entry. PMID- 7786377 TI - Medical students' choices of teaching institutions for residency training. PMID- 7786381 TI - Influencing factors on the injury severity of restrained front seat occupants in car-to-car head-on collisions. AB - The results of 319 cases of belt-restrained front seat car occupants (234 drivers and 85 passengers) from 241 vehicles in car-to-car head-on collisions were examined. Ninety-five occupants were uninjured, 195 sustained a total injury severity of Maximum Abbreviated Injury Score (MAIS) 1-3 and 29, MAIS 4-6. There were 27 fatalities, and the main causes of death were polytrauma and hemorrhage. The main factors influencing occupant injury severity were: the energy equivalent speed (EES); the change of velocity (delta upsilon); the maximum deformation depth; and the collision angle. With an EES > 50 km/h fatal injuries can be expected, and above 60 km/h no occupant remained uninjured. The results of a multivariate analysis were: EES influenced the injury severity at all body locations except the spinal cord; occupant position effected only head injury severity, with drivers being more severely injured; occupant age influenced the injury severity at the thorax, abdomen, and extremities and MAIS as well. Age was a further factor influencing injury severity, e.g. with an EES of 50 km/h the probability of being fatally injured was 30%-45% higher for occupants over 59 years than those under 20. PMID- 7786380 TI - Gender-associated differences in matriculating and graduating medical students. AB - Data from the 1993 Matriculating Student Questionnaire (MSQ) and the 1994 Medical School Graduation Questionnaire (GQ) of the Association of American Medical Colleges were investigated for differences in responses between men and women. Notable differences were discovered, particularly with regard to career plans and experiences during medical school. Findings from the GQ include that a higher proportion of women rated curricular coverage of numerous subjects inadequate and that women students more frequently reported mistreatment during medical school. Women were also more likely than men to work in clinics serving the indigent and to complete a primary care clerkship. Over 30% of the 1994 women seniors, compared with 18% of the men, planned to pursue generalist careers. The authors discuss the gender-associated differences, with reference to previous studies, and conclude that medical educators should ensure that women have access to the same skill-development opportunities that men do and to a humane learning environment. Moreover, educators should examine what adaptations can encourage students of both genders to develop an ethic of "social responsibility." PMID- 7786382 TI - Abandonment of mandatory jail for impaired drivers in Norway and Sweden. AB - In 1988 and 1990, respectively, Norway and Sweden adopted legal reforms including abandonment of mandatory jail sentences for persons driving with BACs above specific limits. Interrupted time-series analysis finds that in both countries traffic deaths diminished simultaneously with the reforms, consistent with the understanding that Scandinavian success in reducing impaired driving does not depend upon mandatory jail. PMID- 7786383 TI - Who's in the car? Passengers as potential interveners in alcohol-involved fatal crashes. AB - This article assesses the promise of motor vehicle passengers as interveners to prevent drinking and driving. It describes data from the U.S. Fatal Accident Reporting System (FARS), which indicate that most alcohol-involved fatally injured drivers (70% of males, 66% of females) were not accompanied by "adult" passengers (16 or older), and alcohol involvement among those passengers present appears to be high (80%). Nonetheless, in approximately 5% to 10% of cases it appears that sober or relatively "unimpaired" passengers could have served as interveners in alcohol-involved driving incidents. Passenger interveners may hold the most promise among teenagers, where passengers in general and unimpaired passengers in particular appear to be most prevalent. PMID- 7786384 TI - A five-year experience with severe injuries in elderly patients. AB - Recent reports of injury in elderly patients document that aggressive care is justified. Our experience indicates that geriatric injury differs from that of other trauma patients. All patients entered into a large urban trauma center registry over a five-year period were analyzed. Variables reviewed included demographics, trauma indices, mechanism of injury, mean number of hospital days, and morbidity and mortality for patients under 60 years old and for geriatric patients defined as those aged 60 and above. There were 3,064 patients in the reviewed group, of whom 243 qualified for geriatric analysis. Blunt injuries in males were the most typical scenario. Failure to use safety belts and alcohol intoxication persist into the geriatric age group (83% and 13%, respectively). Trauma indices including Injury Severity Score (ISS) were slightly greater in the geriatric group (27 versus 23) as compared to younger patients; plus geriatric patients tolerated head injury less well (GCS in those who died 6.7 versus 4.6, respectively; p < 0.001). Mortality in the geriatric group was 31% while being 17.1% in the younger group (p < 0.005). Days in the hospital were 20 for the geriatric compared to 13 for the younger group (p < 0.025). Infections and chest complications were twice as common in the elderly and dysrhythmias were five times more frequent. Elderly patients constitute 8% of the trauma population and suffer a magnitude of injury at least comparable to the general population. Their mortality is approximately 50% above the population as a whole and morbidity twice as common, accounting for the prolonged hospital stay. PMID- 7786386 TI - Field observation of advance warning/advisory signage for passive railway crossings with restricted lateral sightline visibility: an experimental investigation. AB - This study evaluated a newly proposed series of signs intended for passive crossings with restrictions to lateral sightline visibility. These signs provide advance warning of a crossing and the restriction to lateral visibility. In addition, the signs advise motorists to come to a complete stop before crossing. Motorist behaviour was examined before and after installation of these signs at a rural passive crossing. A second site was observed in parallel to control partially for any confounding effects. Results indicated that motorists reduced speed and searched approach quadrants longer at points in the approachway after installation of the signs. However, there was no reliable increase in the number of motorists coming to complete stop, engaging in search behaviours, or classified as safe. The results are discussed in terms of reasons for the lack of compliance with the sign advisory. PMID- 7786385 TI - A study of injury-producing crashes on median divided highways in southwestern Ontario. AB - The University of Western Ontario Accident Research Team investigates every fatal crash, and approximately one out of every 50 personal-injury crash, within a defined geographic area of three counties. Over a seven-year period, the team investigated 107 collisions (62 fatal and 45 personal injury) that occurred on median-divided highways. These crashes were representative of over 2,300 collisions on the highways involving 81 fatalities and injury to over 3,200 vehicle occupants. Vehicle loss of directional control prior to any impact occurred in 55 of the 62 fatal cases and in 36 of the 45 personal-injury cases. In 36 fatal cases and 17 personal-injury cases loss of control was initiated after a vehicle travelled from the roadway onto the gravel shoulder. Rollover collisions were the most frequent collision type investigated and comprised 25 fatal and 25 personal-injury cases. Unrestrained occupants made up 24 of the 29 rollover fatalities with 96% of these unrestrained occupants being ejected from the vehicle. Collision with an oncoming vehicle after median-crossover occurred in 26 fatal cases. These crashes were usually frontal or side impacts characterized by extensive vehicle damage and massive intrusion into the occupant compartment. Severe head injury (AIS 5 or greater) predominated as the cause of death in all collision types. PMID- 7786388 TI - Impact of the 65 mph speed limit on accidents, deaths, and injuries in Illinois. AB - At the end of April 1987, Illinois raised the speed limit from 55 to 65 mph on rural interstates and limited-access highways. This paper examines the effects of this change. It applies ARIMA techniques to a monthly time series of accidents, injuries, and fatalities dating from five years before the limit increase to four years after. Two types of rural highways are examined: those where the speed limit was raised and those where it remained at 55 mph. The impact of higher limits on mean speeds, speed variance, traffic diversion, traffic generation, speed spillover, and issues of benefits and costs are considered. The findings suggest the higher limit led to 300 additional accidents per month in rural Illinois, with associated increases in deaths and injuries. This impact was apparent on both 65 and 55 mph roads. There is some evidence of traffic diversion from 55 to 65 mph highways plus traffic generation and speed spillover. PMID- 7786387 TI - Preventable death classification: interrater reliability and comparison with ISS based survival probability estimates. AB - The purpose of the study was to compare the injury-related threat to survival estimated by the Injury Severity Score (ISS) and a committee of experts. The charts of 116 (73 fatalities and 43 survivors) patients with severe injuries were reviewed. A committee of nine clinicians classified each case as survivable, potentially survivable, and nonsurvivable based on anatomical descriptors, mechanism of injury, and patient's age. Majority was used to determine the final committee classification. Based on the ISS values, cases were classified as survivable (9-24), potentially survivable (25-49), and nonsurvivable (> 49). The results showed poor interrater reliability among the nine clinicians with an overall intraclass correlation coefficient of 0.43. The ISS-based classification had high agreement with the final committee classification (overall weighted kappa = 0.71). Lower agreement was observed for falls and with increasing number of injuries. This study has demonstrated no additional benefit for using a committee to classify injury severity on the basis of anatomical damage over applying ISS-based survival probabilities. The continued use of the ISS is supported. PMID- 7786389 TI - Bicyclist deaths and fatality risk patterns. AB - While there are almost 1,000 bicyclist deaths in the United States every year, there has been little formal analysis of the fatal risk patterns of bicyclists. In large part, this is because there has been little information available on riding exposure. The purpose of this article is to determine and quantify the relative risks of death for bicyclists according to age, gender, and daylight conditions. Relative risks are estimated by comparing data on the characteristics of fatally injured bicyclists with estimates of riding exposure from a recent national survey of bicyclists in the United States. The results suggest substantially higher fatality risks for males, for bicyclists over the age of 44, and for bicyclists who ride after dark. Discussion of the results includes implications regarding differences in the fatal and nonfatal injury risks associated with bicycle use. PMID- 7786390 TI - Safety implications of extending some Canadian Motor Vehicle Safety Standards to light trucks and vans. AB - The primary objective of this research was to evaluate the implications of extending specific Canadian Motor Vehicle Safety Standards (CMVSS) to light trucks and vans (LTVs). This was accomplished through the examination of the potential safety-related benefits of these standards comparing the injury frequencies and severities of the light trucks and vans and the passenger cars (PCs). The standards considered, which currently apply to passenger cars but not to LTVs, are the head restraint (CMVSS 202), side door strength (CMVSS 214), and roof crush strength (CMVSS 216) standards. The comparison was effected by means of logit models developed from multidimensional tables with injury frequency and severity as dependent variables. There are indications that installing head restraints in light trucks and vans could reduce or prevent minor neck injuries and that modest benefits could be achieved by extending the roof crush standard to the LTVs. It was also determined that the side door strength standard may not necessarily be as beneficial to LTVs in conditions in which the vehicle is struck on the side by another LTV. It is suggested that the general public be made aware of the differences in safety standards between LTVs and PCs. PMID- 7786391 TI - Analysis of official economic valuations of traffic accident fatalities in 20 motorized countries. AB - Official economic valuations (costs) of a traffic accident fatality in 20 motorized countries are described. The economic valuation per fatality varies from 0.87 million Norwegian kroner to 17.80 million kroner. The mean value is 5.69 million kroner. An attempt is made to explain the differences in official cost estimates. The valuation method used in estimating the costs has major importance for the level of costs. Recently, a number of motorized countries have accepted the willingness-to-pay approach as the basis for the economic valuation of traffic accident fatalities. In these countries, this has led to major upward revisions of previous cost estimates. PMID- 7786392 TI - The relationship of the retail availability of alcohol and alcohol sales to alcohol-related traffic crashes. AB - The research literature on the relationship of alcohol consumption to motor vehicle crash risk clearly implicates the importance of minimizing the use of alcohol in conjunction with the operation of motor vehicles. However, there has been relatively little documentation of the direct impact of changes in beverage specific alcohol sales on the most common surrogate for alcohol-involved traffic crashes, single-vehicle nighttime fatalities. Similarly, there have been few studies of the relationship between the physical availability of alcohol and fatal crash rates which have concurrently controlled for differences in alcohol sales. Indeed, the possibility that reduced availability might lead to increases rather than decreases in fatal crashes (due to increased driving after drinking) has not been adequately tested. This paper presents a series of analyses of time series cross-sectional data from 38 states over 12 years to evaluate the impact of changes in alcohol sales and the physical availability of alcohol upon single vehicle nighttime fatal crashes. The results of the study showed, first, that independent of a number of economic and demographic covariates, rates of single vehicle nighttime fatal crashes were most strongly related to sales of beer and less so to sales of spirits and wine. Second, net of beverage-specific alcohol sales, the physical availability of alcohol was not related to measurable changes in fatal crash rates. Thus, reductions in availability intended to reduce alcohol sales and problems would not appear to increase traffic-related crashes through increased driving exposure. PMID- 7786393 TI - The identification of mistakes in road accident records: Part 1, Locational variables. AB - The current method of checking police-reported road accident data involves a rigorous process of manual and computer validation, with the objective of removing all the errors that exist on the accident report forms. This paper shows how a geographic information system (GIS) can be used to identify mistakes that exist in several locational variables once this process has been undertaken. It compares items contained on the accident report form with accurate highway feature information obtained from other sources. There were less than 10% of mistakes for the variables of district, speed limit, road class, and road number; less than 20% for junction control, junction detail, and pedestrian crossing facilities; and over 20% for carriageway type. If highway data were routinely entered onto a GIS by all British highway authorities, the above variables might not need to be entered by the police on their accident report forms. PMID- 7786394 TI - The identification of mistakes in road accident records: Part 2, Casualty variables. AB - It has been acknowledged that there are many mistakes in recording the casualty variables on the police accident report forms. This study shows how a computer based linkage of police and hospital records can be used routinely to identify the mistakes for the variables of casualty age, gender, and severity. The level of omissions and misidentifications were 0.4% for gender, 12.2% for severity, and 15.7% for age. The number of records that had age omitted or coded incorrectly was not significantly greater for seriously injured casualties than for those who were slightly injured. This system could be effectively used to code casualty severity using medical information instead of police judgement. PMID- 7786395 TI - Synthesis and biological evaluation of amino-substituted benzo[f]pyrido[4,3-b] and pyrido[3,4-b]quinoxalines: a new class of antineoplastic agents. AB - In order to study the structure-activity relationships in the series of new intercalating polycyclic agents, 1-amino-substituted pyrido[3,4-b]quinoxalines, benzo[f]pyrido[4,3-b]quinoxaline derivatives bearing a dibasic side chain and their benzo[f]pyrido[3,4-b] isomers have been synthesized. Biological evaluation was carried out for topoisomerase I and II inhibition, and for in vitro and in vivo antitumor properties in several models. Results demonstrate that appropriately substituted benzo[f]pyrido[4,3-b]quinoxaline derivatives are inhibitors of topoisomerase I and II, and have significant antitumor properties in various experimental models. In addition, the most active compounds appear to be minimally recognized by tumor cells expressing the multidrug resistance phenotype. PMID- 7786396 TI - Antineoplastic agents 322. synthesis of combretastatin A-4 prodrugs. AB - Combretastatin A-4 (1a), the principal cancer cell growth-inhibitory constituent of the Zulu medicinal plant Combretum caffrum, has been undergoing preclinical development. However, the very limited water solubility of this phenol has complicated drug formation. Hence, derivatives of the combretastatin A-4 (1a) 3' phenol group were prepared for evaluation as possible water-soluble prodrugs. As observed for combretastatin A-4, the sodium salt (1b), potassium salt (1c) and hemisuccinic acid ester (1e) derivatives of phenol 1a were essentially insoluble in water. Indeed, these substances regenerated combretastatin A-4 upon reaction with water. A series of other simple derivatives (1d, 1f-j) proved unsatisfactory in terms of water solubility or stability, or both. The most soluble derivatives evaluated included the ammonium (1l), potassium (1m) and sodium (1n) phosphate salts, where the latter two proved most stable and suitable. Both the potassium (1m) and sodium (1n) phosphate derivatives of combretastatin A-4 were also found to exhibit the requisite biological properties necessary for a useful prodrug. Sodium salt 1n was selected for drug formulation and further pre-clinical development. PMID- 7786397 TI - Synthesis and biological evaluation of basic side chain derivatives of Analog II as pure antiestrogens and antitumor agents. AB - In an effort to prepare effective non-steroidal antiestrogens without intrinsic estrogenicity and with greater antagonism than those of the triarylethylenes (tamoxifen; TAM) four N-substituted (Z)-1,1-dichloro-2-[4-(2-aminoethoxy)phenyl] 3-phenylcyclopropa ne derivatives of the antiestrogen, Analog II, in which the basic side chains contain cyclic (piperidino and piperazino) and non-cyclic (dimethyl amino and diethyl amino) moieties, were synthesized. These compounds were prepared from an intermediate methanesulfonyloxyethoxy side chain ester of 1,1-dichloro-2,3-cis-diphenylcyclopropane using their respective side chain bases in triethylamine and acetonitrile. The gem-dichloro-cis-diarylcyclopropane derivatives were tested for their ability to inhibit the growth-stimulating effect of estradiol on immature mouse uteri and the growth of estrogen receptor (ER)-positive MCF-7E3, ER-negative MDA-MB-231 and the ER-positive MCF-7LY2 antiestrogen-resistant breast cancer cells in culture. The introduction of the various aminoethoxy side chains into Analog II did not improve its ER-binding affinity. Like Analog II, the derivatives did not exhibit any intrinsic estrogenicity, and compounds 9 and 10 antagonized estradiol action more completely than the parent compound. None of the compounds potentiated the uterine weight gain from the stimulating dose of estradiol (0.03 micrograms). Derivatives 9 (150 micrograms), 10 (150 micrograms) and 11 (150 micrograms) had uterine mean weights significantly below the estradiol-treated group, and were better antagonists than Analog II and MER25 at the same concentrations. All compounds exhibited a statistically significant (P < 0.01) reduction in control growth (antitumor activity) from 0.01 to 10 nM concentration in the MCF-7E3 cells. At 10 nM concentration, 8 (66%) and 9 (64%) had the greater antitumor activity over 10 (58%) and 11 (58%). No activity in this cell line was observed for Analog II, TAM and ICI 182,780. Antitumor action was also demonstrated in the MDA-MB-231 cells for all derivatives at 1.0 microM dose, with 9 having the greatest (27%) inhibition of control growth, followed by 8 (20%), 10 (18%) and 11 (12%). Analog II and ICI 182,780 had no antitumor activity in this cell line, while TAM exhibited only 8% inhibition. In the MCF-7E3 cell line at 1.0 microM, 9 exhibited 86% inhibition of the estradiol-stimulated growth (antiestrogenic activity), followed by 8 (64%), 10 (52%) and 11 (21%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7786399 TI - Novel quinone antiproliferative inhibitors of phosphatidylinositol-3-kinase. AB - The inhibition of phosphatidylinositol-3-kinase (PtdIns-3-kinase), protein kinase C and c-Src protein tyrosine kinase by a series of halogenated naphthoquinones and quinoline quinones related to the plant-derived naphthoquinones juglone and methyljuglone, which inhibit protein kinase C, has been investigated. Some of the compounds inhibited PtdIns-3-kinase at micromolar concentrations and below. PtdIns-3-kinase inhibition was time dependent and could be prevented by endogenous thiol. The compounds were only weak inhibitors of PtdIns-4-kinase. Some of the compounds inhibited protein kinase C, but c-Src protein tyrosine kinase was only weakly inhibited. In intact cells, PtdIns-3-kinase was only partly inhibited by concentrations of the halogenated quinones that inhibited cell growth. Some halogenated quinones showed in vivo antitumor activity without accompanying toxicity, while methyljuglone was without in vivo antitumor activity. Halogenated quinones may have multiple biochemical effects in the cell that could contribute to their cytotoxic and antitumor effects. Inhibition of PtdIns-3-kinase by the halogenated quinones may provide a lead for the development of more potent and specific inhibitors. PMID- 7786398 TI - Binding to DNA and cytotoxic evaluation of ascididemin, the major alkaloid from the Mediterranean ascidian Cystodytes dellechiajei. AB - The isolation of ascididemin from the Mediterranean ascidian Cystodytes dellechiajei is described. This alkaloid consists of a planar pentacyclic chromophore which was investigated for its DNA-binding and cytotoxic properties. Spectroscopic measurements provided evidence that the drug intercalates into DNA. DNase I footprinting assays indicated that the binding of ascididemin to GC-rich sequences is favoured over binding to AT-rich and mixed sequences. Chemical probes were used to detect ligand-induced structural changes in DNA. The alkaloid induces a hyper-reactivity of the DNA towards potassium permanganate, but not towards diethylpyrocarbonate, just as is the case with ethidium bromide; it has little effect on the catalytic activities of topoisomerases I and II. Ascididemin exhibits marked cytotoxicity towards human leukaemic cells in vitro and appears to be practically equally toxic for drug-sensitive and multidrug-resistant cell lines. The results suggest that DNA, but not topoisomerases, may represent the critical cellular target at which this marine alkaloid exhibits its potent cytotoxic properties in vitro. PMID- 7786400 TI - Protein malnutrition on suprachiasmatic nucleus cells in rats of three ages. AB - The effects of prenatal and postnatal protein malnutrition on the major and minor somatic axes of the suprachiasmatic nucleus (SCN) cells of the rat were investigated. Female rats were fed either 6%, 8% or 25% casein diet 5 weeks before mating, during gestation and lactation. After weaning the pups were maintained on the same diet until sacrifice at 30, 90 or 220 days of age. The major and minor axes in fusiform, multipolar and ovoid cells were measured in Nissl-stained SCN slices. Although the 8% diet group displayed significant reductions in fusiform and ovoid cells, the 6% diet group showed the most intense reductions in cell size of the three cell types. In the 6% diet group, cell size was significantly lower at 30 days but the difference with the other nutritional groups ameliorated at 90 days and almost reached control values at 220 days. These data suggest that malnutrition maintained during gestation and postnatal life reduces the somatic size of SCN cells. This alteration may be a morphological substrate underlying sleep and behavioral circadian alterations observed in malnourished rats. PMID- 7786403 TI - Distribution of mast cells in the tracheal tissue components of the guinea pig and its bearing on the Schultz-Dale reaction. AB - The distribution of mast cells in the tracheal tissue components and its bearing on anaphylaxis was studied in the guinea pig. According to a statistical analysis (Nested ANOVA) the density found in the tissue elements showed the following gradation (mean +/- SE): muscle (299.7 +/- 61.6 cells/mm3) < serosa (802.7 +/- 131.2 cells/mm3) < submucosa (24283.5 +/- 2549.2) < mucosa (48066.4 cells/mm3 +/- 7837.4). Regardless of their location in tissue elements, the cell density in a zone far from the muscle was larger than in a zone close to the muscle. Considering the histamine release capability of mast cells, the density found either in muscle or in its surroundings does not account for the mediation theory unless some postulates ad hoc are introduced. A direct biophysical mechanism is possibly involved. Another alternative is a reflex to histamine, since there is preponderant location of mast cells in mucosa and submucosa. PMID- 7786401 TI - Increased oxygen radical and high-dietary-carbohydrate pancreatic damage. AB - These data suggest that an improved understanding of the relationship between high dietary carbohydrate and the rate of lipid peroxidation may give some insight into possible treatment modalities for pancreatic damages and may shed light on molecular mechanisms underlying certain pathological processes. High dietary carbohydrate lesions are age related and induced alterations on ceruloplasmin, phospholipids, total proteins, copper and zinc serum levels. Significantly increased serum and pancreatic amylase, and lipoperoxide determinations were observed in 20 month old rats. Cu-Zn superoxide dismutase was decreased in these animals. Daily injection of Cu-Zn superoxide dismutase conjugated with polyethylene glycol (SOD-PEG) prevented the serum and pancreatic changes, indicating that superoxide radical is an important intermediate to high dietary carbohydrate lesion. PMID- 7786404 TI - New electrophysiological approaches to the suprachiasmatic circadian pacemaker. AB - Suprachiasmatic nucleus contains the main circadian pacemaker for mammals rhythmical behavior and physiology. In this paper we revise recent experimental advances on electrophysiological studies to suprachiasmatic circadian pacemaker in rodents. Our growing understanding of the electrophysiology of this nucleus will help to elucidate the clock organization and its input and output mechanisms. PMID- 7786402 TI - Preliminary characterization of epithelial root sheath cells in vitro. AB - Murine root sheath cells from CD-1 mice were isolated and propagated in culture in both monolayer and tridimensional system using basement membrane components as substrata. Cells were grown for a period of seven days. The epithelial cells cultured in monolayer exhibited the typical cobblestone-like feature and also were cytokeratin positive when they were immunostained with the specific antibody. The histological analysis of the cells cultured in basement membrane components revealed differentiated behavior of the cells, and they organized in a round structure with a center of material probably representing keratin. Also the cells differentiated and organized into a squamous stratified epithelia, with a basal, intermedium and superficial layers. The preliminary data obtained with this model could be useful as a new approach to study root formation in the murine periodontum. PMID- 7786405 TI - The molecular basis for N-glycosylation in the 11S globulin (legumin) of lupin seed. AB - Ion exchange-HPLC under denaturing conditions was used to purify to homogeneity the major M(r) 44,000 alpha subunit of lupin seed (Lupinus albus, L.) 11S storage globulin (legumin). The carboxymethylated subunit was digested with trypsin and the peptide fragments separated by reverse phase HPLC. Only one glycosylated peptide reacting with concanavalin A was identified by dot-blotting. Its amino acid sequence allowed the location of this peptide within a highly conserved region in proximity to the N-terminus of the alpha subunits of the 11S globulins from other seeds. The unique presence of a serine residue in a sequence N-X-S of lupin 11S globulin, compared with all other 11S proteins, allows it to be the only protein of this class to bear covalently linked carbohydrate. PMID- 7786406 TI - Purification and characterization of a 60-kDa protein from oat, formerly known as a TCP1-related chaperone. AB - Recently, Mummert et al. [Nature 363, 644-648 (1993)] isolated a proposed TCP1 related chaperone. Here we report several findings concerning the protein which they sequenced. Two similar N-terminal sequences were obtained from this abundant 60-kDa protein. Internal sequences were also acquired by protease digestion. Initially it was believed the protein was able to completely inhibit citrate synthase aggregation, but later purifications demonstrated that the 60-kDa polypeptide lacked both chaperone activity and the previously reported kinase activity [Grimm et al., Planta 178, 199-206 (1989)]. It is now our belief that this protein is neither a chaperone nor a kinase. PMID- 7786408 TI - Expression and purification of recombinant cynomolgus monkey cholesteryl ester transfer protein from Chinese hamster ovary cells. AB - Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl ester from high- and low-density lipoproteins to triglyceride-rich lipoproteins, and reciprocally mediates triglyceride transfer. The gene for cynomolgus monkey CETP was expressed in serum-free CHO culture with 2 micrograms/ml insulin as its only exogenous protein supplement. Cell growth was facilitated by immobilizing the CHO cells in alginate beads. Recombinant CETP (rCETP) was purified 176-fold with a three-step protocol resulting in a 60% final yield as measured by a fluorescent CETP activity assay. Typically, 3.4 mg of rCETP was purified from 1700 ml of media by affinity-gel chromatography involving Reactive Red 120 (RR120) followed by concanavalin A Sepharose 4B and rechromatography on RR120. SDS-PAGE shows a single broad band of M(r) ranging from 68,000 to 74,000 which immunoreacts in Western blot analysis. Amino acid analysis and protein sequencing of the purified protein agree with the theoretical amino acid composition and sequence of cynomolgus CETP. PMID- 7786407 TI - Complete amino acid sequence of Proteus mirabilis PR catalase. Occurrence of a methionine sulfone in the close proximity of the active site. AB - The catalase of Proteus mirabilis PR, a peroxide-resistant (PR) mutant of Proteus mirabilis, binds strongly NADPH, which is a unique property among known bacterial catalases. The enzyme subunit consists of 484 amino acid residues for a mass of 55,647 daltons. The complete amino acid sequence was resolved through the combination of protein sequencing, mass spectrometry, and nucleotide sequencing of a PCR fragment. The sequence obtained was compared with that of other known catalases. Amino acids of the active site are all conserved as well as essential residues involved in NADPH binding. Among the amino acids interacting with the heme, a methionine sulfone was found at position 53, in place of a valine in most other catalases. The origin of oxidation of this methionine is unknown, but the presence of this modification could change iron accessibility by large substrates or inhibitors. This posttranslational modification was also demonstrated in the wild-type P. mirabilis catalase. PMID- 7786409 TI - Symmetric interspecies hybrids of mouse and human hemoglobin: molecular basis of their abnormal oxygen affinity. AB - Interspecies hybrids of HbA and Hb from mouse C57BL/10 [alpha 2M beta 2H and alpha 2H beta 2M (H = human, M = mouse)], representing 19 and 27 sequence differences per alpha beta dimers (as compared with human alpha beta dimer) have been generated in vitro. The efficiency of the assembly of the interspecies hybrids by the alloplex intermediate pathway is about twofold higher than the low pH-mediated subunit approach. The interspecies hybrids exhibit a cooperative O2 binding. The intrinsic O2 affinity of mouse Hb is slightly lower than HbA, while the 2,3-diphosphoglycerate (DPG) effect is comparable. Interestingly, the interspecies hybrid alpha 2M beta 2H has high O2 affinity (compared to either human or mouse Hb), while the interspecies hybrid alpha 2H beta 2M exhibits a very low O2 affinity. These results suggest that the mouse beta chain generates a tetramer with very low oxygen affinity. However, the complementarity of the mouse alpha and beta chains generates a set of unique interactions that compensate for the low-oxygen-affinity propensity of the mouse beta chain. DPG binds the tetramer in the central cavity formed by the two beta subunits, hence the DPG effects on the interspecies hybrids should be as in the parent molecule. However, the results of the present study demonstrate that the DPG binding pocket is influenced by the nature of the alpha chain present in the tetramer. The mouse alpha chain reduces considerably the DPG right shift of the O2 affinity of the human beta-chain containing hybrid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786410 TI - Chemical modification of tryptophan residues in alpha-neurotoxins from Ophiophagus hannah (king cobra) venom. AB - Two alpha-neurotoxins, Oh-4 and Oh-7, from the king cobra (Ophiophagus hannah) venom were subjected to Trp modification with 2-nitrophenylsulfenyl chloride (NPS Cl). One major NPS derivative was isolated from the modified mixtures of Oh-4 and two from Oh-7 by HPLC. Amino acid analysis and sequence determination revealed that Trp-27 in Oh-4, and Trp-30 and Trp-26 and 30 in the two Oh-7 derivatives, were modified, respectively. Sulfenylation of Trp-27 in Oh-4 caused about 70% drop in lethal toxicity and nicotinic acetylcholine receptor-binding activity. Modification of Trp-30 in Oh-7 resulted in the decrease of lethal toxicity by 36% and binding activity by 61%. The activities were further lost when the conserved Trp-26 in Oh-7 was modified. Sulfenylation of the Trp residues did not significantly affect the secondary structure of the toxins as revealed by the CD spectra. These results indicate that the Trp residues in these two long alpha neurotoxins may be involved in the receptor binding. PMID- 7786412 TI - PDI-, PPI- and chaperone-catalyzed refolding of recombinant human IL-2 and GM CSF. AB - The studies on PDI-, PPI- and chaperone-catalyzed refolding of recombinant human IL-2 and GM-CSF show that PDI can prevent the mismatch of disulfide bonds and formation of aggregates by interchains linkage; furthermore, PDI can correct the mismatching of disulfide bonds in IL-2 isomers. PPI can increase the rate of folding reaction while chaperone can prevent the aggregation during the folding process. In addition, there is a synergistic effect between them. PMID- 7786413 TI - Stable oncogenic transformation induced by microcell-mediated gene transfer. AB - Oncogenes have been identified using DNA-mediated transfection, but the size of the transferable and unrearranged DNA, gene rearrangement and amplification which occur during the transfection process limit the use of the techniques. We have evaluated microcell-mediated gene transfer techniques for the transfer and analysis of dominant oncogenes. MNNG-HOS, a transformed human cell line which contained the met oncogene mapping to human chromosome 7 was infected with retroviruses carrying drug resistance markers and used to optimize microcell preparation and transfer. Stable and drug-resistant hybrids containing single human chromosomes as well as the foci of the transformed cells containing the activated met oncogene and intact human chromosomes were obtained. Hybridization analysis with probes (i.e. col1A2, pJ3.11) mapping up to 1 Mb away from met shows that the cells from the individual foci contain different amounts of apparently unrearranged human DNA associated with the oncogene, and the microcell-generated transformants retain more distal markers than those observed in either DNA- or chromosome-mediated transfers. In conjunction with other techniques, microcell fusion should be useful for gene mapping as well as the study of gene function and expression in cell transformation and malignancy. PMID- 7786414 TI - [Deficiency in public services and breeding of Aedes aegypti in Venezuela]. PMID- 7786415 TI - [Attitudes of Bolivian pharmacy distributors in a case of diarrhea]. AB - In order to learn the recommendations given for a case of diarrhea by persons who sell medications at pharmacies, interviewers visited pharmacies in three Bolivian cities and said they had a child suffering from diarrhea. Less than 2% of the vendors recommended using oral rehydration salts, increasing fluid intake, or consulting a doctor. Most of them recommended antibiotics, antidiarrheals, or both. Oral rehydration salts were not available in nearly two-thirds of the establishments visited, and those that had the salts rarely offered them. This study revealed the lack of integration of these professionals into the Health Secretariat's training program, and as a result activities were initiated to solve this problem. PMID- 7786411 TI - Tau protein kinase I/GSK-3 beta/kinase FA in heparin phosphorylates tau on Ser199, Thr231, Ser235, Ser262, Ser369, and Ser400 sites phosphorylated in Alzheimer disease brain. AB - Previously, tau protein kinase I/glycogen synthase kinase-3 beta/kinase FA(TPKI/GSK-3 beta/FA) was identified as a brain microtubule-associated tau kinase possibly involved in the Alzheimer disease-like phosphorylation of tau. In this report, we find that the TPKI/GSK-3 beta/FA can be stimulated to phosphorylate brain tau up to 8.5 mol of phosphates per mol of protein by heparin, a polyanion compound. Tryptic digestion of 32P-labeled tau followed by high-performance liquid chromatography and high-voltage electrophoresis/thin layer chromatography reveals 12 phosphopeptides. Phosphoamino acid analysis together with sequential manual Edman degradation and peptide sequence analysis further reveals that TPKI/GSK-3 beta/FA after heparin potentiation phosphorylates tau on sites of Ser199, Thr231, Ser235, Ser262, Ser396, and Ser400, which are potential sites abnormally phosphorylated in Alzheimer tau and potent sites responsible for reducing microtubule binding possibly involved in neuronal degeneration. The results provide initial evidence that TPKI/GSK-3 beta/FA after heparin potentiation may represent one of the most potent systems possibly involved in the abnormal phosphorylation of PHF-tau and neuronal degeneration in Alzheimer disease brains. PMID- 7786417 TI - [Sixth meeting of Directors of National Reference Laboratories of AIDS]. PMID- 7786416 TI - [Central American project of local action to prevent violence against women]. PMID- 7786419 TI - Ruptured intracranial aneurysms. PMID- 7786418 TI - Cervical myelopathy caused by pseudogout. AB - A case of pseudogout manifesting as a cervical myelopathy is presented. Surgery can offer the definitive treatment with removal of the compressing crystalline mass. This diagnosis should be considered in a progressive myelopathy in the elderly person shown to have extradural compression, even in the absence of other stigmata of gout. PMID- 7786420 TI - Trigeminal neuralgia treated by microvascular decompression: a long-term follow up study. AB - Since 1976, 133 patients treated by posterior fossa microvascular decompression (MVD) for trigeminal neuralgia (TN) have been followed-up prospectively to determine the incidence of recurrent TN. The follow-up period was between 6 months and 15 years, with 60 patients having been follow-up for more than 5 years. Of these patients, 71% have remained pain-free, while 29% have suffered a major or minor recurrence. Of patients who developed recurrent TN, 90% did so within 2 years of operation. No patients who were pain-free up to 5 years after operation subsequently developed recurrent TN. Recurrent TN was more likely to occur when the operative findings did not show nerve root distortion or displacement, or when the age of onset was less than 35 years. PMID- 7786421 TI - CT assessment of subarachnoid haemorrhage. A comparison between different CT methods of grading subarachnoid haemorrhage. AB - A number of different CT classifications of subarachnoid haemorrhage (SAH) were applied to a consecutive series of 50 patients with aneurysmal SAH. The best correlation with delayed ischaemic deficits (DID) was obtained with a score formed by the sum of the individual cisternal grades except that of the cortical subarachnoid space. The findings emphasize the significance of the extent of the SAH, rather than the presence of a localized cisternal clot with regard to the development of DID. PMID- 7786422 TI - Post-traumatic brain abscess: experience of 36 patients. AB - Thirty-six patients with post-traumatic brain abscess were managed over 18 years. They constituted 9.3% of all brain abscesses encountered during the same period. The head injury was associated with an external compound fracture in 20, internal compounding in three and was closed in 13 patients. The mean interval between the time of injury to presentation with an abscess was 113 days. This did not differ significantly in patients with closed and compound head injury, and amongst patients who had wound sepsis and with clean wounds after the injury. The occurrence of focal neurological deficit was more frequent in patients with a closed injury (p < 0.05). Twenty patients underwent primary excision of the abscess with recurrence of the abscess in one patient. Of the 14 patients in whom the abscess was initially aspirated, eight patients required a subsequent excision. Excision was required in 18 patients (94.7%) with external compound injury, five (50%) of those with closed injury and in all patients with internally compound injuries. Two patients had 'coned' and died before they could be operated upon. The operative mortality in the absence of signs of herniation preoperatively was 12.5% in patient with compound injury and none among patients with closed head injury. PMID- 7786423 TI - Motivation and internal markets in a National Health Service. PMID- 7786424 TI - Fatal postoperative 'pituitary apoplexy': its cause and management. AB - Two cases of giant pituitary tumours are reported. The patients underwent transcranial operation, one by the pterional and one by the subfrontal route. Only partial resection of the tumour was possible in each instance for various reasons. Acute worsening of the clinical condition in the immediate postoperative phase led to reoperation in both patients. In one case the reoperation was carried out within 45 min of the closure of the wound and in the other after 12 h. Massive swelling of the tumour with evidence of haemorrhagic infarction was a surprise finding. After a turbulent postoperative phase, both patients died. We postulate that these patients developed pituitary apoplexy of the residual tumours. PMID- 7786426 TI - The presence of progesterone receptors in arachnoid granulations and in the lining of arachnoid cysts: its relevance to expression of progesterone receptors in meningiomas. AB - Progesterone receptors (PR) were identified with an enzyme immunoassay in cytosols from human arachnoid granulations and arachnoid cysts. Meningiomas presumably originate from subdural endothelium which is abundantly present in these structures. In the three cases studied, oestrogen receptors were absent. The presence of PR in subdural endothelium may provide further ground for the expression of PR in meningiomas. PMID- 7786425 TI - Pituitary function after selective adenomectomy for Cushing's disease. AB - This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F: 8 M, mean age 33.6 years) undergoing transphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy, repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 155 and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery. PMID- 7786428 TI - Inflammatory pseudotumour of the central nervous system: clinicopathological study of one case and review of the literature. AB - A 58-year-old male who had been diagnosed as having polymyositis was found to have a mass in the fourth ventricle. This mass showed features of an inflammatory pseudotumor. This lesion has been described in many parts of the body including the central nervous system. This case showed some features different from the previously reported cases in the central nervous system (i.e. presence of necrosis and association with polymyositis) which may throw some light on the pathogenesis of the condition. Inflammatory pseudotumour is most likely to be caused by an exaggerated immunological process and is sometimes associated with high levels of serum immunoglobulin. PMID- 7786427 TI - Rathke's cleft cysts within a growth hormone producing pituitary adenoma. AB - Two cases with a unique association of Rathke's cleft cysts and a growth hormone secreting pituitary adenoma in the same tumour tissue are reported. The embryological pathogenesis, diagnostic evaluation and treatment of these lesions are discussed. PMID- 7786429 TI - The surgical treatment of Chiari malformation association with atlantoaxial dislocation. AB - Five cases of Chiari malformation associated with atlantoaxial dislocation are presented. A lateral plate and screw fixation was performed in all cases. Reversal foramen magnotomy was performed in three cases and two patients underwent the conventional posterior bony decompression for Chiari malformation. In an average postoperative follow-up period of 8 months (range 3 months to 2 years) neurological symptoms and signs improved in all patients, with radiological and clinical evidence of bony union and stability of the craniovertebral region. The surgical problems encountered in such cases where a posterior decompression was required in addition to a fixation procedure are enumerated in this report. The advantages of the proposed operations are described. PMID- 7786430 TI - Results of cortical resection for intractable epilepsy using intra-operative corticography without chronic intracranial recording. AB - Twenty-four patients with intractable partial epilepsy underwent surgery between 1969 and 1988. Localization was by non-invasive means using scalp EEG and CT. In 12 cases the focus was temporal and in eight frontal. Craniotomy was undertaken with intraoperative electrocorticography (ECoG). Ten cases had a standard temporal lobectomy, seven a topectomy, four topectomy with tumour excision and one tumour excision alone. Two cases did not have a resection. Pathology revealed a mass lesion in 12 cases, hippocampal sclerosis in two and gliosis in six. Mean length of follow-up was 7.4 was. Fourteen patients (64%) were seizure free, two (9%) almost seizure free, four (18%) had worthwhile improvement and two (9%) no improvement. Of the temporal resections, 9 out of 12 (75%) were seizure free and of the extratemporal resections 5 out of 10 (50%) were seizure free. Removal of a mass lesion carried the most favourable prognosis for seizure outcome: 10 our of 12 (83%) of the cases with mass lesions, but 3 out of 6 (50%) of the cases with gliosis were seizure free. In two of the frontal resections removal of tumour resulted in disappearance of contralateral frontal independent spikes. It is concluded that where sufficient information exists to localize seizure activity by non-invasive means, invasive recording is unnecessary. The utility of intraoperative ECoG is discussed. It may be of limited use in cases of standard resection of when a mass lesion is present, but ECoG can prove useful to delineate the epileptogenic area in cases where there is o mass lesion and the results can still be rewarding. PMID- 7786431 TI - CT-directed perineural infiltration in the localization of radicular pain in a patient with neurofibromatosis. AB - Computed tomography-guided infiltration of lumbar or sacral nerve roots with local anaesthetic can be a valuable aid in localizing the spinal level from which radicular pain originates especially when multiple abnormalities are present. This is illustrated by the case of a young woman with neurofibromatosis complaining of sciatica. PMID- 7786432 TI - Cavernous haemangioma in the cavernous sinus. AB - A case of intracavernous sinus cavernous hemangioma is reported. The tumor was totally resected en masse. The management of the lesion and technical issues concerning the surgery are discussed. PMID- 7786434 TI - Subdural empyema in an HIV positive patient. AB - A subdural empyema with a Salmonella species as the likely causative organism is presented. We believe that this is the first reported case of such an infection in an HIV positive patient. The difficulties in treatment and diagnosis are discussed. PMID- 7786435 TI - Parasellar chondrosarcoma: total excision improves prognosis. PMID- 7786433 TI - Supratentorial haemangioblastoma not associated with Von Hippel Lindau complex or polycythaemia: case report and literature review. AB - Solitary or multiple supratentorial haemangioblastomas are rare and may be associated with Von Hippel Lindau complex (VHLC), polycythaemia or a family history of VHLC. An extensive review of the literature (1902-1992) has revealed 112 cases. They account for 2-8% of all haemangioblastomas and are commonly intraparenchymatous (86.8%) and infrequently intraventricular (6.6%). However, a meningeal location 5.6%) is extremely rare. Only one case of a solitary leptomeningeal haemangioblastoma has previously been reported and this was associated with a family and personal history of VHLC, cerebellar haemangioblastoma and renal carcinoma. We report a solitary solid left parietal leptomeningeal haemangioblastoma mimicking a meningioma or a secondary deposit on computed tomography in a 72-year-old male. There were no manifestations of or a family history of VHLC or polycythaemia. PMID- 7786436 TI - Intracerebral haemorrhage due to amphetamine abuse: report of two cases with underlying arteriovenous malformations. AB - Amphetamine abuse may be complicated by intracerebral, subdural or subarachnoid haemorrhage. The causative mechanism is probably a combination of vasculitis and induced hypertension. Most cases of intracerebral haemorrhage are subcortical. Only one case of amphetamine-induced intracerebral haematoma where there was also an underlying arteriovenous malformation has been previously reported. We report two cases of intracerebral haematoma due to amphetamine abuse whether an underlying AVM was found at the time of surgery. This possibility should be considered in cases of amphetamine-induced intracerebral haemorrhage. PMID- 7786437 TI - Suprasellar granular-cell tumour, presenting with intraventricular haemorrhage. AB - A case of suprasellar granular-cell tumour (GCT), presenting with intraventricular haemorrhage is described. The authors emphasize the exceptional character of spontaneous haemorrhage for a GCT, although haemorrhagic state during surgery has often been reported and may hinder total removal. Preoperative arteriography discloses a suprasellar blush in half of the cases. This facilitates the preoperative diagnosis. By taking special preoperative and operative precautions against haemorrhage complete removal can be carried out provided there is no encasement of the optic chiasm. PMID- 7786438 TI - Acute promyelocytic leukemia is a distinct subset of acute myelocytic leukemia with unique clinicopathologic characteristics including longer duration of relapse free survival: experience in 13 cases. AB - Acute promyelocytic leukemia(APL) is a subtype of acute myelocytic leukemia(AML) associated with unique features such as the presence of atypical promyelocytes and bleeding tendency due to disseminated intravascular coagulation(DIC). In a retrospective study, we analyzed 96 cases of AML seen at our hospital between June, 1989 and December 1993. Thirteen cases of APL(14%) were identified and their clinicopathologic characteristics were analyzed. The 86 cases of other types of AML served as controls. The distinct clinicopathologic features of APL as contrasted to other types of AML included younger age of patients, shorter duration of symptom before diagnosis, higher level of albumin at presentation, and a higher proportion of patients having coagulation abnormalities (75 vs. 25%). Bone marrow cellularity was higher in APL when compared to other types of AML (100 vs. 90%, P = 0.013). Of 13 patients with APL, 4 died of bleeding/sepsis between days 2 to 4 after admission. Seven of 9 patients who received induction therapy achieved complete remission(CR). CR rate in APL was similar to other types of AML (78 vs. 64%, P = 0.743). Five of seven patients who achieved CR remain in continuous CR at 9+ to 42+ months. CR duration is significantly longer in APL when compared to other types of AML (P = 0.029). In conclusion, this study showed that APL is a distinct entity among subtypes of AML with clinically significant bleeding tendency and rapidly fatal course if untreated. With appropriate antileukemic therapy, CR can be achieved in the majority of patients and the patients show a longer duration of CR when compared to other types of AML. PMID- 7786439 TI - Familial clustering of hepatitis B and C viruses in Korea. AB - In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea. PMID- 7786440 TI - Bilateral primary pigmented nodular adrenocortical disease--a case of report describing a rare cause of Cushing's syndrome. AB - A case of Cushing's syndrome due to bilateral pigmented nodular adrenal disease in a 35-year-old male is presented. The adrenals showed multiple, black, variable sized nodules. Histologically the cells contained lipofuscin and either had a clear cytoplasm or an eosinophilic cytoplasm with a prominent nucleus. Lymphocytic infiltration and fatty metaplasia within the nodules are two of the prominent histological features. There is extreme internodular atrophy which suggests that primary pigmented nodular adrenocortical disease is a non adrenocorticotropic hormone dependent condition. Since the disorder appears to involve primarily the cortex of both adrenals, the treatment of choice is bilateral adrenalectomy followed by steroid replacement. The characteristic clinicopathological manifestations that separate this diagnosis from other types of adrenal disease are also discussed. This is the first reported case in Korea to be documented with the pertinent clinicopathological findings. PMID- 7786441 TI - Adult T-cell leukemia/lymphoma in a Korean--a case report. AB - The clinicopathologic features of a Korean patient with adult T-cell leukemia/lymphoma(ATLL) are presented. A 51-year-old man, who has lived in Korea since birth, had multiple cutaneous nodules and multiple lymphadenopathy for the previous two months. A histopathologic study of the lymph node and skin lesion revealed T-cell non-Hodgkin's lymphoma of pleomorphic type, medium and large cell type. Peripheral blood examination showed leukemic features with 30% of abnormal lymphoid cells. HTLV-I proviral DNA pX region was detected in the DNA from peripheral blood mononuclear cells(PBMC) and the specific gag, pol, and env HTLV I sequences were detected in the lymph node using polymerase chain reaction technique. Human T-cell leukemia/lymphoma type I(HTLV-I) antibodies were present in the serum. An immunophenotypic study of the lymph node revealed CD4 positive and CD8 negative helper/inducer T cell type surface markers. This case is the acute type, i.e. prototypic ATLL. He was treated with an intensive chemotherapy including cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone. Despite initial transient improvement, the tumor progressed after three cycles of the regimen and became refractory to further chemotherapy. These clinicopathologic findings, including the immunophenotypic analysis, established with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma. PMID- 7786442 TI - Ipsilateral synchronous renal cell carcinoma and transitional cell carcinoma. AB - The simultaneous occurrence of renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) in the same kidney is unusual. We report a 53-year-old man with ipsilateral synchronous renal adenocarcinoma and renal pelvic transitional cell carcinoma with severe hypercalcemia and a huge staghorn calculus in the opposite kidney. The patient was admitted to the hospital because of left flank pain and intermittent fever which he had had for 2 months. Computerized tomography revealed a huge stone in the right kidney and a mass in the upper pole with an irregular calcified pelvis in the left enlarged kidney. Left radical nephrectomy was done. A section of the specimen revealed a renal cell carcinoma located at the upper pole and a papillary transitional cell carcinoma arising from the renal pelvis. This is a rare case of combined renal malignancies. PMID- 7786443 TI - Plexiform malignant peripheral nerve sheath tumor(MPNST) in infancy and childhood -a case report. AB - We present a congenital plexiform cellular tumor with high mitotic activities arising in the right thigh of a 3-days-old infant. This subcutaneous tumor measured 6.5 x 4.5 cm in diameter with multinodular, whitish, elastic cut surface. Microscopically, the tumor was composed of fascicles of closely packed uniform spindle cells with frequent nuclear palisadings. The most remarkable finding was frequent mitoses(4-5/10 HPF). The tumor cells were strongly positive for S-100 protein, myelin basic protein and vimentin, and weakly positive for Leu 7. On electron microscopic examination, the spindle cells were found to be surrounded by continuous basal lamina and had interlocking long cytoplasmic processes. Although the prognosis of this tumor is difficult to predict, aggressive behavior such as recurrences may be suggested, but it is less likely to be metastatic. Further accumulation of similar unusual cases may be helpful in evaluation of its biologic behavior. PMID- 7786444 TI - Gene cloning of the human cytomegalovirus (HCMV) antigen reactive with the serum from a HCMV-infected patient. AB - The human cytomegalovirus(HCMV) gene encoding the protein reactive with the sera of HCMV-infected patient was cloned and characterized. A reactive phage clone was screened from a lambda gt11 expression library of cDNA of HCMV AD169 strain using HCMV-infected patient sera. The recombinant protein was expressed as 138 kDa fusion protein with beta-galactosidase, which was reactive with IgM or IgG HCMV antibody-positive sera, but not with anti-HCMV antibody-negative sera. A homology search of the DNA sequence of the cloned gene with HCMV AD169 sequences revealed that it was composed of 709 base pairs spanning between 0.174 and 0.177 map units of the UL32 region of the HCMV AD169 strain genome. This position corresponded to a part of the gene encoding 150 kDa phosphoprotein-(pp150), a major tegument protein, which was reported as an immunogenic protein which evoked strong and longstanding antibody response and had no sequence homology with the proteins of other herpesviruses. These results suggested that pp150 was an immunogenic protein in natural HCMV infection and therefore this clone was regarded as a useful candidate for developing an antigen for the serodiagnosis of HCMV. PMID- 7786445 TI - CYP1A2 activity as a risk factor for bladder cancer. AB - CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p < 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3 demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer. PMID- 7786446 TI - Modulation of transglutaminase expression in rat skeletal muscle by induction of atrophy and endurance training. AB - The persistence of muscle fiber number regardless of size reduction in muscle atrophy has not yet been fully explained. For the mechanism inherent in skeletal muscle tissues for preventing cellular death, the protective function of muscle tissue through transglutaminases has been tested, since the enzyme is responsible for structural stabilization and participates in signal transduction. In the present experiment, hindlimb suspension for two weeks caused a marked muscle atrophy in Wistar female rats. Comparison of muscle weight and histological analysis showed that suspension-induced atrophy in the hindlimb was more prominent in the soleus muscle, comprised mainly of type I fiber than that in the plantaris muscle of type II fibers. The immunohistochemical analysis with antitransglutaminase C antibody (anti TGase C Ab) showed that some atrophic bundles of soleus muscle were positively reacted with the antibody. The anti TGase C Ab-reactive substances were observed to disappear significantly after endurance exercise, indicating their characteristic atrophy-dependency. The enzymatic analysis of transglutaminase showed the increase in activity in the atrophic soleus muscle tissue, compared with that in the normal or exercise trained muscle tissues. From these results, the expression of TGase in the atrophic muscle is suggested to be the possible marker for muscle atrophy and its expression is probably related with the protective mechanism of the muscle tissue to prevent further cellular damage in the atrophic process. PMID- 7786448 TI - Bilateral fractures of Hydroflex penile prostheses: an unusual complication. AB - We report bilaterally fractured Hydroflex implants in 2 patients. One fracture was complete and three were incomplete. All the fractures occurred at the junction of the rear reservoir and the inflation chamber. PMID- 7786447 TI - Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells. AB - We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms. PMID- 7786449 TI - Five cases of cytomegalovirus infection detected by in situ hybridization and antigenemia assay. AB - We report five cases of cytomegalovirus infection in immunocompromised patients which were detected by either cytomegalovirus antigenemia assay or in situ hybridization. Four cases had leukemia and the other had chronic renal failure. All the three BMT recipients suffered from GvHD. Interestingly, there was an unique case of CMV disease without a history of BMT, which reminded us that CMV could attack immunocompromised patients who had not undergone transplantation, too. Four out of five cases died. We think that cytomegalovirus infection or disease should not be regarded as a minor problem in post-transplantation infection in Korea. PMID- 7786450 TI - Job-sharing a clinical teacher's position: an evaluation. AB - The aim of this study was to evaluate the effects on staff of having two teachers share one clinical teaching position in their intensive care unit (ICU). Three, six and 12 months after the job-sharing arrangement was initiated, an 11 item questionnaire was distributed to 26 students in post-registration critical care courses, 41 clinical staff in ICU and 9 RN-managers with responsibilities for the unit. The overall response rate to the three questionnaires was 58%. All groups agreed that job-sharing was a viable alternative to full-time work. Three months after the shared position was initiated, there was uncertainty about the consistency of the teachers' performance and the adequacy of communication between them. Nine months later, there was a high level of positive responses to all areas of the teachers' performance. Most respondents felt they could approach either teacher and that more diverse ideas were generated by having two people in the teaching position. PMID- 7786451 TI - Measuring pain in neonates: evaluating an instrument and developing a common language. AB - This paper describes the development and evaluation of the Pain Assessment Tool (PAT), a scoring system that was developed by a group of neonatal nurses to assess neonates' pain. To test the practical application of the tool and to compare the scoring system with nurses' subjective pain assessments, a pilot study was conducted with a sample of 20 neonates during the 24 hours following their surgery. The study found that PAT effectively quantified neonates' pain and that PAT scores reflected nurses' perceptions of the pain experienced by neonates. Based on the PAT scores, 15 babies experienced discomfort that required nursing comfort measures and eight babies needed both comfort measures and analgesia to relieve pain. Recommendations for future use of the Pain Assessment Tool are discussed. PMID- 7786452 TI - Domestic violence: are we listening? Do we see? AB - This article reports on a study of female victims of abuse who had been hospitalised for treatment of injuries inflicted by their spouses. A phenomenological approach was adopted wherein four women were interviewed to elicit their perceptions of their last hospital experience. Four major themes emerged from analysis of the interview data, these were that the women consistently experienced: disengagement and loss of status; disempowerment and lack of control; stigma and social isolation and a sense of being misunderstood. The results of the study are discussed in relation to women's expectations of nurses' attitudes and nursing interventions. PMID- 7786453 TI - The impact of critical incidents in paediatric hospitals: a review. AB - Literature addressing critical incidents involving hospitalised children is reviewed and circumstances that produce critical incidents are discussed. It is argued that critical incidents often have a major impact on children and their families and on staff, and particularly nursing staff, in paediatric intensive care and burns, oncology and emergency units. Some strategies for assisting children, families and staff to cope with severe trauma, life-threatening illness and death in paediatric hospitals are presented. PMID- 7786454 TI - Peer review--how does it work? PMID- 7786458 TI - Relinquishing the sick role: convalescence and rehabilitation. AB - This paper examines the problems of patients who have been considered by their doctors to have received adequate rehabilitation and to be ready to relinquish the sick role. The sick role is discussed in its historical context and convalescence and rehabilitation are considered as alternative approaches to medical and nursing care. It is argued that many patients leaving hospital are frightened because they do not feel well and they will receive little if any follow-up or support after discharge. It is the author's belief that many patients need to convalesce because the very essence of their being is still ill. PMID- 7786457 TI - Blood letting for BSL: the effects of timing and sites on blood volume. AB - The purpose of this study was to establish the most appropriate timing and site for obtaining an adequate volume of blood for accurate measurement of blood sugar levels by blood glucose monitors. The 248 samples of blood used in the study were collected from 18 men and 16 women recruited from a group of people with type II diabetes mellitus who were attending an outpatient Diabetes Centre. Neither the timing between lancing and collecting the blood nor the sites from which blood was obtained significantly affected the volume of blood samples. Sufficient blood to give an accurate measure of blood sugar levels from monitors requiring 30, 15 18 and five microlitres of blood was obtained from 37%, 65% and 98% of the procedures respectively. PMID- 7786456 TI - Gender bias in cardiology: are women missing out on PTCA? AB - The purpose of this study was to determine if there were differences in the ages of women and men who underwent percutaneous transluminal coronary angioplasty (PTCA), in the duration of PTCA procedures performed on women and men and in the percentage of women and men treated with PTCA relative to the gender distribution of deaths attributed to coronary heart disease. The study was conducted as a retrospective audit of the operation records of 959 PTCA procedures performed over a two year period in a cardiology clinic in a Sydney teaching hospital. Results indicate that, on average, women were older than men when they underwent PTCA, that the average duration of the procedure was longer for women than men and that disproportionately fewer women aged 65 and over were treated with PTCA. The results suggest that gender bias in the delivery of PTCA cannot be discounted and that further research is needed on the clinical needs of women with coronary heart disease. PMID- 7786455 TI - EDPS and clinical depression. PMID- 7786461 TI - The clinician and the academic: nursing experience and academic study. AB - This study was conducted at an Australian university which uses telephone group tutorials to enable off-campus students to link their academic and practice worlds. Audiotapes of the content of the 16 teletutorials in one first year unit of the university's Bachelor of Nursing course and interviews with the tutor and 10 of the registered nurses who were student participants were transcribed for analysis. Analysis of the tapes and texts revealed that there was discernible tension between the students' roles as 'expert' clinicians and 'novice' students and, further, that this was a reflection of inherent tension between faculty rhetoric, reality/belief and practice. It became evident that these tensions would become problematic and impact on both the tutor's and students' perceptions of the course. PMID- 7786462 TI - Conversations with researchers. Interview by Natalie Newman. PMID- 7786459 TI - Patients' experiences of nursing interventions during hospitalisation with an AIDS-defining illness. AB - The aim of this phenomenologically informed study was to explore the experience of being hospitalised with an AIDS-defining illness. Eight men recently hospitalised with an AIDS-defining illness were asked at interview to describe the meaning of AIDS for them and the nursing interventions they experienced as helpful and unhelpful while they were in hospital. The findings pertaining to participants' experiences of nursing interventions are highlighted in this paper. Overall, the interventions experienced as helpful were those which the participants interpreted as being motivated by care. Conversely, the interventions described as unhelpful were those that suggested to the participants a lack of care on the part of nurses. The main implications of patients' experiences for nursing practice are discussed. PMID- 7786463 TI - Tracing lost research participants. AB - This paper discusses search strategies that were used to locate research participants with whom researchers had lost contact during a 13 year longitudinal study. The information that proved to be most useful in tracing 'lost' participants was a record of correct names and next of kin. The most cost effective method of re-establishing contact was via the telephone. PMID- 7786464 TI - [Alcohol and traffic safety--study of epidemiology (II. 1990/1991 status]. AB - With the co-operation of a further 13 institutes and as a continuation of our own epidemiological-statistical survey, we recorded the total and relative distribution (frequency profile) of the blood alcohol concentration of car drivers for the 3rd quarter 1990 and the 1st quarter 1991. The participating institutes recorded almost 27,000 blood samples and compared them with results of the first part of the study (1989). The survey dealt separately with sex-, age- and time of day-distribution of drivers involved and not involved in road accidents. One of our repeatedly presented field research into the problem of "alcohol and road safety", once again, provided to be a useful method in the run up to the unprejudiced alcohol test which we are striving for. We noticed characteristic changes in the frequency profiles of the old and the new counties (Bundeslander) in Germany in the 1st (1989) and the 2nd (1990/91) report of the study. The results of Police supervisory operations in the administrative district of Cologne have basically given useful indications as to their epidemiological-statistical value as evidence. PMID- 7786460 TI - The time has come the Walrus said, to speak of many things... PMID- 7786465 TI - [Indicators for alcohol abuse in female drunk drivers. (Comparative study with alcohol intoxicated male automobile drivers)]. AB - Women account for about 12% of all cases of drink driving in German cities. Little is known about their drinking behaviour and the extent of their alcohol misuse. In order that these questions may be clarified, three major studies were evaluated. In these studies, additional indicators for alcohol misuse such as GGT or methanol and acetone+isopropanol or indeed CDT, GGT, methanol and acetone+isopropanol were measured in blood samples. The results were compared with studies of the same kind on male car drivers. There were no significant differences in the ages of males and females. However, there were no differences at all regarding the frequency of the blood alcohol levels or the CDT. Indicators levels of chronic alcohol abuse, such als GGT levels above 70 U/L, methanol levels above 10.00 mg/kg or acetone+isopropanol concentrations above 9.00 mg/kg were approximately the same with women as they were with men. This demonstrates an increasing similarity amongst male and female DWI drivers regarding the drinking behaviour and alcohol abuse. PMID- 7786466 TI - [Arterial and venous alcohol elimination in 10 polytrauma patients]. AB - Alcohol elimination was examined in 10 patients involved in accidents while intoxicated. The influence of trauma, particularly polytrauma resulting in haemorrhage shock and its therapeutic treatment were analysed. The blood alcohol concentrations were determined according to the usual forensic criteria (2 alcohol dehydrogenase and 2 gas chromatography measurements). Observation periods ranged from 3 hours 45 minutes to 12 hours 35 minutes, with blood being drawn at intervals ranging from 45 minutes to 185 minutes (on average 70 minutes). Results of two patients (delta 60 = 0.22/1000/h and 0.28/1000/h) who only had 3 venous drawn and results of a deceased patient from whom only four arterial samples could be obtained (beta 60 = 0.21/1000/h) were disregarded when working out the average values. The blood alcohol curve plateaued in the case of the deceased patient as well as in the case of a patient whose hepatic circulation was curtailed for approximately half an hour during surgery. The blood alcohol curves for the remaining patients for uniformly linear with beta 60 values between 0.17/1000/h and 0.21/1000/h (mean = 0.18/1000/h +/- 0.01) in arterial samples and 0.18/1000/h and 0.21/1000/h (mean = 0.18/1000/h +/- 0.01) in venous samples. Given our results and the existing literature, we feel that retrograde calculations of the BAC can be justified in patients with polytrauma, despite the small number of patients included in the study. Naturally, the usual forensic criteria have to be taken into account, as well as individual situations. Examples that can be mentioned here are liver failure or curtailment of hepatic circulation during surgery. PMID- 7786467 TI - [Intake of addictive drugs and traffic safety--a report of experiences of the Vienna federal police department]. AB - Urine samples of 27 individuals with extremely conspicuous behaviour in road traffic were analysed by means of the Abbott ADx-analyser for cocaine metabolites, cannabinoids and opiates. Gas chromatography/mass spectrometry (GC/MS) confirmed positive results. 52% of those 26 positive samples confirmed the simultaneous consumption of two drugs. In 16% all three drugs tested could be found positive, exceeding the threshold values given for the tests hundred fold. Without exception, all 25 urine samples found positive in the ADx-analyser belonged to young people (22 males, 3 females) with 48% of them born between 1968 and 1970. 84% of tested people had previous convictions and 68% had drug addiction records. We also see this project as the beginning of continuing investigations of other drugs and pharmaceuticals. Given the fact that 25 out of 27 samples were found to be positive we most certainly detected nothing but the "tip of the iceberg". We should strive, in conjunction with other European countries, for a political solution to the problem of the illegal and legal consumption of drugs and pharmaceuticals and their effect on driving performance. PMID- 7786469 TI - Potentiometric butyrylcholine sensor for organophosphate pesticides. AB - A highly sensitive potentiometric butyrylcholine (BuCh) sensor based on plasticized poly(vinyl chloride) membrane was fabricated using tetrakis (3,5 bis[2-methoxy-hexafluoro-methyl] phenyl) borate (HFPB) as a cation exchanger. The sensor showed a Nernstian response from 10(-1) M to 10(-6) M for BuCh. The detection limit of the sensor was 1.8 x 10(-7) M. The potential stability, lifetime and detection limit of the BuCh-sensor were improved in comparison with corresponding parameters of BuCh-sensors using prepared other cation exchangers. This improvement was proved to be due to higher hydrophobicity of the cation exchanger, HFPB. Enzyme activity of butyrylcholinesterase (BuChE) was determined by the BuCh-sensor fabricated. Since the selectivity coefficient of the BuCh sensor for BuCh against a product of the enzyme reaction, choline, was as low as 6.3 x 10(-3), the sensor was not affected by interference from choline even when the enzyme reaction proceeded up to about 80%. Michaelis parameters for the BuChE reaction were obtained by the sensor. Determinations of organophosphate pesticides, 2,2-dichlorovinyldimethylphosphate and o-(4-bromo-2-chlorophenyl)o ethyl S-propylphosphothiolate) were conducted by measuring inhibition of enzyme activity. The enzyme reaction rate was related to the concentration of pesticides. Pesticides were successfully determined between micromole and sub nanomole levels by the BuCh-sensor. PMID- 7786468 TI - [Unethical advertising?--The promille killer and alcohol tester]. PMID- 7786470 TI - Retained activities of some membrane proteins in stable lipid bilayers on a solid support. AB - Highly stable lipid bilayers, composed of biologically relevant lipids such as phosphatidylcholine, phosphatidylethanolamine and cholesterol, were formed on platinum surfaces. Bacteriorhodopsin isolated from purple membrane (PM) from Halobacterium halobium, cytochrome oxidase from bovine heart, acetylcholinesterase from bovine brain and the nicotinic acetylcholine receptor from Torpedo electric organ were also incorporated into these reconstituted membranes. The proteins retained their biological activities. Some of them were active several weeks after the reconstitution and after several cycles of assay, washing and storage. PMID- 7786471 TI - An approach for an immunoaffinity AIDS sensor using the conservative region of the HIV envelope protein (gp41) and its monoclonal antibody. AB - A monoclonal antibody for the conservative region of gp41, which is one of the HIV envelope proteins, was produced. The antigen determining site of gp41 was examined using the epitope mapping technique, followed by an enzyme linked immunosorbent assay. Some peptides had comparable affinities for the monoclonal antibody, but the peptide EGIEE, having a slightly weaker immunoaffinity than gp41, was the most preferable for the construction of an immunoaffinity AIDS sensor. For the detection of gp41, EGIEE was labelled with catalase and used as a mimic antigen; it was bound to the antibody present on an immuno-membrane and, due to the replacement reaction of the mimic antigen by gp41, indirect quantitative measurement of gp41 was possible using an oxygen electrode. Anti gp41 antibody was also detected using a mimic antibody, which was chemically modified with polyethylene glycol. An immunoaffinity AIDS sensor was constructed using the mimic molecules which were tailored to have a suitable immunoaffinity for HIV antigen and/or antibody. PMID- 7786472 TI - Integrated implantable device for long-term glucose monitoring. AB - In this study we report the development of an integrated implantable device for glucose monitoring. The dimensions of the device (5.0 x 7.0 x 1.5 cm) allow implantation under the abdominal skin of a large animal for in vivo evaluation of sensor performance. The experimental set-up includes amperometric glucose biosensor, a miniature potentiostat, an FM signal transmitter, a power supply and an antenna and receiver linked to a computer-based data acquisition system. The device performance was evaluated in vitro using a ten-day continuous test and other long-term operation experiments. The biosensor was tested in different model solutions that simulated the physiological environment in which it will be ultimately used. A linear response to glucose concentration was obtained up to 25 mM glucose, with a sensitivity of less than 0.5 microA/mM. The ability of the biosensor to measure glucose levels in serum was also tested, and a good correlation demonstrated between glucose serum levels measured by routine technique and those measured using the biosensor (R2 = 0.993; slope = 0.996). Initial results obtained from the short-term subcutaneous implantation of the sensor demonstrate its potential for the monitoring of glucose concentration in vivo. PMID- 7786474 TI - A matter of some sensitivity. AB - The development of sensitive chromatographic and spectroscopic techniques for the isolation and structure determination of natural products has greatly facilitated phytochemical investigations. Chemical investigations of herbarium material have resulted in the isolation of indole, quinoline and isoquinoline alkaloids from a wide number of plants. Examples of novel natural products from higher plants are given and include alkaloids, terpenoids, phenolics and quinones. Some plants investigated have not yielded the types of constituents which would have been predicted from them. Plant tissue cultures provide alternative sources of biologically active compounds and examples investigated include Cinchona, Ailanthus, Brucea and Artemisia for antiprotozoal compounds and Datura for tropane alkaloids. Biological tests are useful for bioassay-guided fractionation of plant extracts and examples of the isolation of a series of natural products with antiprotozoal and cytotoxic activities are given. Chemical and biological investigations into the traditional medicine Dragon's blood (Croton lechleri) from S. America and a Chinese prescription for the treatment of atopic eczema are described. The use of radio-ligand binding assays for the detection of a wide range of biological activities is discussed. Sensitivity of chemical and biological techniques has greatly improved prospects for finding new drug entities from plants and for investigating traditional medicines. Basic phytochemical investigations should continue to be encouraged especially in view of the rapid loss of plant species. PMID- 7786473 TI - Specific binding assay for biotin based on enzyme channelling with direct electron transfer electrochemical detection using horseradish peroxidase. AB - A model 'homogeneous' format enzyme channelling specific binding assay for biotin based on peroxide-sensitive horseradish peroxidase mediatorless enzyme electrodes is described. The procedure involved the immobilisation of avidin onto the surface of printed carbon horseradish peroxidase (HRP) enzyme electrodes and the competitive binding of biotin and biotinylated glucose oxidase. Upon addition of glucose, hydrogen peroxide was generated via the glucose oxidase label. Direct electron transfer between the electrodes and HRP resulted in the detection of H2O2 by electroenzymic reduction at +50 mV vs Ag/AgCl. The cathodic current response could be measured in the presence of excess biotinylated glucose oxidase by incorporation of catalase in homogeneous solution to scavenge H2O2 generated in the bulk before it diffused to the electrode surface. The assay showed greatest sensitivity over the range of biotin concentrations 0.07 to 2 micrograms ml-1 in the presence of 10 micrograms ml-1 excess biotinylated glucose oxidase in the bulk solution. PMID- 7786475 TI - Diterpenoids from Isodon eriocalyx var. laxiflora. AB - Three new, seco-ent-kaurane diterpenoids, laxiflorins A, B and C, together with four known diterpenoids eriocalyxin B, oriodonin, and maeocrystals A and B, were isolated from the leaves of Isodon eriocalyx var. laxiflora. Their structures were assigned by a combination of one- and two-dimensional NMR techniques and computer modeling calculations. Laxiflorin C displayed weak cytotoxic activity. PMID- 7786476 TI - Polyandrol, a C19 quassinoid from Castela polyandra. PMID- 7786477 TI - Triterpenoid saponins from Clematis chinensis. AB - From the roots of Clematis chinensis, two new triterpenoid saponins, named clematichinenoside A and B, were isolated and their structures were elucidated as 3-O-beta-D-ribopyranosyl-(1-3)-alpha-L-rhamnopyranosyl-(1-2)-alpha -L- arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester and 3-O-beta-D glucopyranosyl-(1-4)-beta-D-ribopyranosyl-(1-3)-alpha-L - rhamnopyranosyl-(1-2) alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl-(1-4)-beta-D glucopyranosyl-(1-6)- beta-D-glucopyranosyl ester, respectively. In addition oleanolic acid, hederagenin and seven known saponins were obtained. PMID- 7786478 TI - Isolation of triterpene saponins from Gypsophila capillaris. AB - Four novel triterpenoid saponins have been isolated from Gypsophila capillaris. Three were monodesmosidic: 3 beta-hydroxyolean-12-en-23,28-dioic acid 28-O-[beta D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->2)] [beta-D galactopyranosyl(1-->6)]beta-D-glucopyranoside, 3 beta-hydroxyolean-12-en-23-oxo 28-oic acid 28-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->3)] [beta-D-glucopyranosyl(1-->6)]beta-D-galactopyranoside, 3 beta-hydroxyolean-12-en 23,28-dioic acid 28-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1- >3)] [beta-D-glucopyranosyl(1-->6)]beta-D-galactopyranoside. The fourth was bisdesmosidic: 3 beta-hydroxyolean-12-en-23,28-dioic acid 23-O-beta-D glucopyranosyl-28-O-[beta-D-glucopyranosyl-(1-->2)-beta-D- galactopyranosyl-(1- >3)][beta-D-glucopyranosyl-(1-->6)]beta-D- galactopyranoside. The structures of the compounds were elucidated by 1D and 2D NMR techniques and from other spectroscopic evidence. PMID- 7786479 TI - Triterpene saponins from Aster yunnanensis. AB - Four new triterpene saponins, asteryunnanosides A, B, C and D, have been isolated from Aster yunnanensis and their structures deduced as 2 alpha,3 beta,23 trihydroxyolean-12-en-28-oic acid-28-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D glucopyranoside, 2 alpha,3 beta,23-trihydroxyolean-12-en-28-oic acid-28-O-beta-D glucopyranosyl-(1-->2)-beta-D-glucopyranoside, 2 alpha,3 beta-dihydroxyolean-12 en-28-oic acid-28-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside and 2 alpha,3 beta-dihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl-(1-->2) beta-D-glucopyranoside, respectively, by means of spectral and chemical data. PMID- 7786480 TI - A bidesmosidic triterpene saponin from Cephalaria transsylvanica. AB - The structure of cephalaria saponin B, isolated from Cephalaria transsylvanica was elucidated as 3-O-([beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1- >2)-beta-D- xylopyranosyl]-[28-O-beta-D-glucopyranosyl])-3beta,23-dihydroxy 12(13)-oleanene-28-oic acid. PMID- 7786481 TI - A ferulic acid ester of sucrose and other constituents of Bhesa paniculata. AB - A novel derivative of sucrose, beta-(3,6-di-O-feruloyl)-fructofuranosyl-alpha (2,3,4,6-tetra-O-ac etyl)- glucopyranoside, was isolated from the wood of Bhesa paniculata. Its structure was determined by a combination of 2D 1H-1H and 1H-13C correlation NMR spectroscopy. The known compounds, glycerol 1-9',12' octadecadienoate, beta-sitosterol, (+/-)-pinoresinol, methyl 3,4 dihydroxybenzoate, 4-hydroxy-3-methoxybenzoic acid, anofinic acid and 2-(1' methylethenyl)-benzofuran-5-carboxylic acid were also isolated. PMID- 7786483 TI - (S)-13-hydroxygeranylgeraniol-derived furanoditerpenes from Bifurcaria bifurcata. AB - Two new diterpenes were isolated from a sample of the brown alga Bifurcaria bifurcata collected from Brittany on the Atlantic coast and their structures established by spectroscopic methods. The new diterpenes are derived from (S)-13 hydroxygeranylgeraniol by terminal cyclization and oxidation leading to a furan-3 yl ring or a beta,gamma-epoxy-gamma-lactone. One of them showed a cytotoxic effect to fertilized sea urchin eggs. The chemical shifts of the methyl groups and quaternary carbons in (S)-13-hydroxygeranylgeraniol have been revised to take account of the results obtained in a 2D NMR long-range C-H correlation experiment and the absolute configuration at C-13 determined for the first time. The geographical variation in the diterpenoid composition of B. bifurcata was also studied. PMID- 7786482 TI - Antiallergic dimeric prenylbenzoquinones from Ehretia microphylla. AB - The ethyl acetate-soluble portion of the MeOH extract of Ehretia microphylla showed inhibitory activity on exocytosis in antigen-stimulated rat basophils. The bioassay-guided separation of this fraction afforded five biologically active compounds. By means of chemical and spectroscopic methods, the structures of these compounds, which include microphyllone, a unique dimeric prenylbenzoquinone, and its congeners, were elucidated. PMID- 7786484 TI - Two cytotoxic pentacyclic triterpenoids from Nerium oleander. PMID- 7786486 TI - Saponins from Hacquetia epipactis. AB - Four new estersaponins were isolated from hacquetia epipactis. Using GC-MS, FAB MS and various 2D-NMR techniques they were identified as 3-O-[beta-D glucopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1--> 3)]- beta-D glucuronopyranosyl-(1-->)]-21-acetyl-22-(2-methylbutyryl)- barringtogenol C (hacquetiasaponin 1), the corresponding 21-(2-acetoxy-2-methylbutyryl)-22-acetyl derivative (hacquetiasaponin 2), 3-O-[beta-D-glucopyranosyl-(1-->2)-[alpha-L arabinopyranosyl- (1-->3)]-beta-D-glucuronopyranosyl-(1-->)]-21-acetyl-22-(2 methylb utyryl)- R1-barrigenol (hacquetiasaponin 3) and its corresponding 21-(2 acetoxy-2-methylbutyryl)-22-acetyl-derivative (hacquetiasaponin 4). PMID- 7786485 TI - Mazusaponins I-IV, triterpene saponins from Mazus miquelii. AB - From whole plants of Mazus miquelii, four new saponins designated as mazusaponins I-IV and a known saponin, ilexoside VIII, were isolated and the structures of the new compounds elucidated as 3-O-alpha-L-arabinopyranosyl siaresinolic acid 28-O beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L arabinopyranosyl siaresinolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D glucopyranosyl ester and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D glucopyranosyl ester, respectively, by spectroscopic data and chemical evidence. PMID- 7786487 TI - Steroidal glycosides from Cynanchum caudatum. AB - The aerial part of Cynanchum caudatum afforded 10 new pregnane glycosides which had sarcostin or deacylmetaplexigenin as the aglycone moiety. The structures of these compounds were elucidated by spectroscopic methods and from chemical evidence. PMID- 7786488 TI - Cucurbitacin glycosides from Caput nigri. AB - The chemical structures of cabenosides I-L were investigated. These are four of the 12 cucurbitacin glycosides isolated from 'Cabeca-de-negro', the roots of Caput nigri. By means of chemical analyses the structures of cabenosides I-L were elucidated as 10 alpha-cucurbit-5-ene-3 beta,11 alpha,20S,24 xi,25-pentaol [3, 25 di-O-beta-D-glucopyranoside, and 3-O-beta-D-glucopyranosyl-(1-2)-beta-D glucopyranosyl (sophorosyl), 25-O-beta-D-glucopyranoside], and 10 alpha-cucurbit 5,20,24-triene-11-oxo-3 beta,26-diol [3-O-beta-D-glucopyranosyl-(1-6)-beta-D glucopyranosyl (gentiobiosyl), 26-O-beta-D-glucopyranoside and 3,26-di-O gentiobioside], respectively. PMID- 7786489 TI - Cucurbitacin glycosides from Cabeca-de-negro. AB - Five cucurbitacin glycosides named cabenosides D-L were isolated from 'Cabeca-de negro', the roots of Caput nigri. Among them, the structures of cabenosides D-H were elucidated as 10 alpha-cucurbit-5-en-11-oxo-3 beta,24R,25-triol-3-O-beta-D glucopyranoside, 10 alpha-cucurbit-5-en-24-oxo-3 beta, 11 alpha,25-triol-25-O beta-D- glucopyranosyl, [3,O-beta-D-glucopyranoside, 3-O-beta-D-glucopyranosyl-(1 2)-beta-D-glucopyranoside, 3-O-beta-D-glucopyranosyl-(1-6)-beta-D glucopyranoside] and 10 alpha-cucurbit-5-en-11,24-dioxo-3 beta,25-diol-25-O-beta D- glucopyranosyl, 3-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside, respectively, on the basis of chemical and spectral evidence. PMID- 7786491 TI - Structural features of fungal beta-D-glucans for the efficient inhibition of the initiation of virus infection on Nicotiana tabacum. AB - Glucans of fungal origin have been shown to inhibit the early stages of infection of Nicotiana by numerous viruses of different taxonomic groups. Several glucans were isolated from the cell walls of Phytophthora parasitica, Phytophthora megasperma f. sp. glycinea (Pmg) and Fusarium oxysporum, and their antiviral activity compared on tobacco leaves inoculated with tobacco mosaic virus. These polysaccharides consist of a mixture of (1-->3)(1-->6)-beta-D-glucans with M(r) varying from 1.1 x 10(3) to 2 x 10(6). Requirements for a prominent antiviral activity of the fungal polysaccharides are a beta-(1-->3)(1-->6)-D-glucan structure with mono-, di-, tri- or tetra-glucosidic side branches attached to a linear main chain of beta-(1-->3)-linked-D-glucose residues. Very high activity is correlated with a high degree of branching at position 6 and with the size and glycosidic nature of the side chains. The molecular masses and the organized structure of fungal beta-D-glucans are not essential for their antiviral activity. The structural motif for antiviral activity in Nicotiana is distinct from that required for elicitation of phytoalexins in soybean cotyledons. PMID- 7786492 TI - Molluscicidal saponins from Catunaregam nilotica. AB - Two new saponins were isolated from the fruits of Catunaregam nilotica Stapf, syn. Lachnosiphonium nilotica; Randia nilotica; Xeromphis nilotica. Their structures were determined mainly by spectroscopic methods as 3- O-[O-alpha-L rhamnopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1 -->3)]- beta-D glucopyranosyl]oleanolic acid and 28-O-beta-D- glucopyranosyl-3-O-[O-alpha-L rhamnopyranosyl-(1-->3)-O[O-beta-D- glucopyranosyl]-beta-D glycopyranosyl]oleanolate. The monodesmosidic saponin is a potent molluscicide against the schistosomiasis transmitting snail Biomphalaria glabrata with a LC50 value of 3 ppm. In addition two known saponins, 3-O-[2', 3'-di-O-(beta-D glucopyranosyl)-beta-D- glucopyranosyl]oleanolic acid and 3-O-[O-beta-D glucopyranosyl(1-->3)- beta-D-glucopyranosyl]oleanolic acid, were identified and their molluscicidal activity determined, the LC50 values being 26 and 3 ppm, respectively. Initial molluscicidal screening of the crude water and ethanol extracts revealed 100% snail mortality at concentrations of 100 and 50 ppm, respectively. The haemolytic activity of the molluscicidal saponins was determined as well and the HC50 values towards bovine erythrocytes found to be 3 ppm for the new saponin, and 16 and 2 ppm, respectively, for the two known saponins. PMID- 7786493 TI - Whose genome is it anyway? PMID- 7786490 TI - Two cationic peroxidases from cell walls of Araucaria araucana seeds. AB - We have previously reported the purification and partial characterization of two cationic peroxidases from the cell walls of seeds and seedlings of the South American conifer, Araucaria araucana. In this work, we have studied the amino acid composition and NH2-terminal sequences of both enzymes. We also compare the data obtained from these analyses with those reported for other plant peroxidases. The two peroxidases are similar in their amino acid compositions. Both are particularly rich in glycine, which comprises more than 30% of the amino acid residues. The content of serine is also high, ca 17%. The two enzymes are different in their content of arginine, alanine, valine, phenylalanine and threonine. Both peroxidases have identical NH2-terminal sequences, indicating that the two proteins are genetically related and probably are isoforms of the same kind of peroxidase. The amino acid composition and NH2-terminal sequence analyses showed marked differences from the cationic peroxidases from turnip and horseradish. PMID- 7786494 TI - Application of enzymes to the synthesis of surfactants. AB - Recent progress in the application of isolated enzymes to the preparation of surface-active compounds demonstrates the feasibility of an alternative to organosynthetic methods. Processes such as the syntheses of monoglycerides, sugar fatty acid esters, (lyso)phospholipids, anomerically pure alkyl glycosides and amino acid-based surfactants are discussed, highlighting some of the advantages of enzymatic methods over conventional organic syntheses and whole-cell systems. PMID- 7786495 TI - Manipulating the immune response in allergic disease: targeting CD4+ T cells. AB - CD4+ T lymphocytes play an important role in the induction and maintenance of inflammatory responses in allergic diseases. In this review, we examine some of the recent developments that have expanded our knowledge of how T cells recognize and respond to common environmental allergens. In addition, we discuss the role of allergen-derived peptides and their derivatives in the modulation of the immunological activity of allergen-specific T cells, and their potential application for immune intervention. It appears that the ability to redress the balance between qualitatively different subsets of functional components of the immune system may guide the development of therapy. PMID- 7786496 TI - Microbiological criteria for retail foods. Professional Food Microbiology Group (PFMG) of the Institute of Food Science and Technology (IFST). AB - This article proposes that microbiological criteria should only be drawn up and applied to foods if there is a full understanding and consideration of raw material selection, production process, packaging and finished product characteristics. The combined knowledge and expertise of public sector microbiologists and food industry microbiologists and technologists need to be harnessed in the establishment of such criteria. In this manner, microbiological criteria could be derived to the overall benefit of the consumer. A meeting of the Society for Applied Bacteriology held in November 1994 considered the issue of microbiological standards for foods and, in this paper, the recently formed PFMG presents an opinion on the 'Provisional microbiological guidelines' published by the Food Surveillance Group of the Public Health Laboratory Service. PMID- 7786497 TI - An assessment of environmental factors influencing acid tolerance and sensitivity in Escherichia coli, Salmonella spp. and other enterobacteria. AB - Environmental factors such as temperature, pH and nutrient level affect enterobacterial acid sensitivity, as do the presence of phosphate and Na+ and the extent of aeration. The mechanisms governing these effects are partially understood and the involvement of phoE, fur and atp in acid tolerance, of phoE, envZ, tonB, (p)ppGpp and cAMP in salt-induced acid sensitivity and of rpoS in stationary-phase acid tolerance are of particular interest. It should be noted that surface attachment enhances acid resistance. PMID- 7786498 TI - Sensitivity of Campylobacter spp. to irradiation in poultry meat. AB - The sensitivity of Campylobacter jejuni (three strains), Camp. coli (three strains), Camp. fetus (one strain) and Camp. lari (one strain) to irradiation in poultry meat was investigated. There was no significant difference in the counts obtained on Blood or Skirrows agar. Preston agar gave a significantly lower recovery of the pathogens after irradiation so these results were not included in calculations of D10 values. The D10 values ranged from 0.12 to 0.25 kGy and there was a significant difference in the radiation sensitivity between different Campylobacter spp. and within strains of the same species. These values indicate that Campylobacter spp. are more radiation-sensitive than Salmonella and Listeria monocytogenes irradiated under similar conditions. Therefore irradiation treatments suggested to eliminate the latter from poultry carcasses would also be sufficient to remove Campylobacter. PMID- 7786499 TI - Efficacy of the E-test in evaluating the antimicrobial susceptibility of anaerobic bacteria of veterinary interest. AB - A study was made of the sensitivity of 39 clinical isolates of anaerobic bacteria to 10 antimicrobial agents. Minimal inhibitory concentrations (MICs) were calculated using a new method--the E-test (AB Biodisk, Solna, Sweden)--and compared with those obtained using the conventional agar dilution method. Agreement between the MICs obtained by the two methods with a variation of +/- 2 dilutions was 78.7%. The E-test, though less sensitive than the conventional agar dilution method, may be of value in clinical veterinary practice when rapid selection of treatment for a given infectious process is required. PMID- 7786500 TI - X-ray microanalysis of chlorhexidine-treated cells of Saccharomyces cerevisiae. AB - The use of energy dispersive analysis of X-rays (EDAX) to identify and quantify the presence of chlorhexidine diacetate (CHA) within Saccharomyces cerevisiae cells was examined. Chlorine was used as the elemental marker tag. Saccharomyces cerevisiae cells exposed to 1000 micrograms ml-1 CHA took up increasing amounts of CHA over a time period of 30 s to 30 min. Electron probe micro-analysis was employed to examine the specific accumulation of CHA across the treated cells. These results showed that CHA was distributed evenly between the cell wall, cytoplasm and vacuoles of cells pre-treated with this concentration of CHA for 30 min. The EDAX system therefore provides a useful tool for examining the qualitative and quantitative effects of chlorhexidine on yeast cells, although quantitative data must be interpreted with caution. PMID- 7786501 TI - Energy dispersive analysis of X-rays study of the distribution of chlorhexidine diacetate and cetylpyridinium chloride on the Pseudomonas aeruginosa bacteriophage F116. AB - Using an energy dispersive analyser of X-rays fitted to a scanning electron microscope, chlorhexidine was shown not to bind onto F116 bacteriophage, unlike cetylpyridinium chloride, which possibly penetrated the phage. This could explain the difference in viricidal activity between the two compounds. PMID- 7786503 TI - Differentiation of Yersinia pestis and Y. pseudotuberculosis by SDS-PAGE analysis of lipopolysaccharide. PMID- 7786502 TI - The detection of Salmonella in skimmed milk powder enrichments using conventional methods and immunomagnetic separation. AB - Skimmed milk powders were spiked with one of three Salmonella serovars and incubated in buffered peptone water for 24 h. No false-negative results were obtained by immunomagnetic separation (IMS), compared to seven for selenite cysteine, one for Muller-Kauffmann tetrathionate and two for Rappaport Vassiliadis enrichment broths. Salmonella virchow was detected and enumerated during the pre-enrichment incubation by IMS and indirect conductance techniques. The Salm. virchow cell number did not increase after 12 h incubation and remained at 3 x 10(6) cfu ml-1. IMS was able to capture Salm. virchow cells at cell numbers ca 50 ml-1 in the presence of a 1000 greater number of non-salmonella cells. PMID- 7786504 TI - Discrepancy between Penner serotyping and polymerase chain reaction fingerprinting of Campylobacter isolated from poultry and other animal sources. AB - Thirty-four Campylobacter jejuni or coli strains, isolated from various livestock and darkling beetles from two Dutch poultry farms during different broiler production cycles, were subjected to Penner serotyping and polymerase chain reaction (PCR) fingerprint analysis. Ten different Penner serotypes were determined in the isolates. Visual scoring of the PCR fingerprints resulted in 14 clearly different profiles. Some strains with identical Penner serotypes exhibited different PCR fingerprints and conversely strains with different serotypes produced identical PCR fingerprints. Discrepancies between Penner serotyping and PCR fingerprinting were most obvious between isolates from different animal sources. Indications for the occurrence of genomic rearrangements were found. The inconsistency between serotyping and fingerprinting of Campylobacter strains suggests that conventional typing methods should be used in combination with fingerprinting if the epidemiological factors that contribute to Campylobacter colonization of live chickens are to be assessed reliably. PMID- 7786505 TI - Evaluation of methods for the isolation and detection of Escherichia coli O157 in minced beef. AB - This study has evaluated enrichment and detection procedures for the isolation and detection of Escherichia coli O157 inoculated into minced beef. The use of a 24 h enrichment in modified EC broth containing novobiocin allowed low numbers of contaminating cells to multiply to levels detectable on culture media and by ELISA test kits. Total analysis time was reduced by the use of the Dynabead immunomagnetic separation system. The use of the Petrifilm Test Kit-HEC for E. coli O157:H7 and Organon Teknika EHEC-TEK system detected low numbers of contaminating cells following enrichment and reduced analysis time by 1 d. The incorporation of cefixime and tellurite into Sorbitol MacConkey Agar increased the rate and ease of isolation of E. coli O157 and its use is therefore recommended. PMID- 7786506 TI - Formation of viable but nonculturable Salmonella during starvation in chemically defined solutions. AB - Salmonella enteritidis enters a viable-but-nonculturable state when exposed to starvation in aquatic environments. This study determined starvation survival of this pathogen in chemically defined solutions and tested the ability of nonselective enrichment to detect viable-but-nonculturable cells. Starvation of Salm. enteritidis at 7 degrees C in 7.35 mmol l-1 potassium phosphate buffer resulted in complete loss of culturability after 5 weeks with maintenance of a substrate-responsive population of over 10,000 cell ml-1. Starvation at 21 degrees C and starvation in saline solutions or lower concentrations of phosphate buffer resulted in prolonged survival of a culturable population although this population was lower than the total viable population. Enrichment using lactose broth did not allow resuscitation of viable-but-nonculturable cells even after 5 d of incubation at 35 degrees C. PMID- 7786508 TI - Virulence factors of Listeria monocytogenes. PMID- 7786507 TI - Antimicrobial drug resistance in Staphylococcus aureus isolated from cattle in Brazil. AB - Isolates of Staphylococcus aureus obtained from apparently healthy cattle in the State of Paraiba, Brazil were characterized in relation to resistance to 21 antimicrobial agents. Among the 46 isolates obtained, resistance to penicillin was most frequent, followed by resistance to cadmium, streptomycin, arsenate, tetracycline, mercury, erythromycin and kanamycin/neomycin. All isolates were susceptible to fusidic acid, ethidium bromide, cetrimide, chloramphenicol, benzalkonium chloride, doxycycline, gentamicin, methicillin, minocycline, novobiocin, rifamycin, tylosin and vancomycin. Only six isolates were susceptible to all the drugs tested. With respect to the antibiotics, multi-resistant isolates were uncommon. These results are probably a consequence of the peculiarities of local drug usage pressures. In relation to metal ions, resistance to mercury was rare while resistance to arsenate was relatively frequent, which contrasts with the situation for human Staph. aureus strains. After treatment with ethidium bromide, elimination of resistance to penicillin, tetracycline, streptomycin, erythromycin and cadmium was observed, which was consistent with the genetic determinants being plasmid-borne. PMID- 7786509 TI - Detection of FRNA coliphages in groundwater. PMID- 7786510 TI - The action of muscles in swimming fish. PMID- 7786511 TI - Glutamate-immunoreactivity in identified vagal afferent terminals of the cat: a study combining horseradish peroxidase tracing and postembedding electron microscopic immunogold staining. AB - Using electron microscopic immunohistochemistry we have shown that strong glutamate-immunoreactivity (glutamate-ir) is present in neuronal cell bodies of the nodose ganglion, axons in the tractus solitarius and afferent terminals in the nucleus tractus solitarii. Vagal afferent fibres were specifically labelled by transganglionic retrograde transport of horseradish peroxidase (HRP). Fifty seven per cent of the HRP-labelled terminals in the dorsomedial medulla were found to contain a high level of glutamate-ir, suggesting that a population of vagal afferent fibres uses glutamate as a neurotransmitter substance. There were no apparent ultrastructural differences between glutamate-ir and non-glutamate-ir vagal afferent terminals, both classes mainly containing rounded vesicles and forming asymmetric synapses. However, some difference in their preference for postsynaptic target was noted. The great majority (83%) of non-glutamate-ir vagal afferent terminals made axodendritic synapses, but only just over half (57%) of the glutamate-ir vagal terminals made synaptic contact with dendrites. Approximately 13% of the HRP-labelled terminals were found to make synaptic contact with HRP-labelled dendrites or soma of motoneurones of the dorsal vagal motor nucleus, confirming the existence of monosynaptic connections between vagal afferent fibres and vagal motoneurones. PMID- 7786513 TI - Comparison of synovial PO2 and sympathetic vasoconstrictor responses in normal and acutely inflamed rabbit knee joints. AB - Experiments were performed to assess the effect of acute inflammation of the rabbit knee joint on the partial pressure of oxygen in synovial fluid (Ps,O2) and nerve-mediated vasoconstrictor responses of articular blood vessels. With the hypodermic needle oxygen electrode sited within the synovial cavity in the posterior region of the knee joint, mean (+/- S.E.M.). Ps,O2 was 37.4 +/- 3.6 mmHg (n = 10) in the inflamed group, which differed significantly (P < 0.05) from that occurring in the normal group from a different series (48.2 +/- 3.1 mmHg; n = 18). Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode into the joint cavity of the inflamed knee, as in the normal knee. The lowest values were observed close to articular cartilage. Absolute blood flow was measured using radiolabelled microspheres whilst relative changes in blood flow were assessed using laser Doppler flowmetry. The former technique showed that the inflamed joints had a significantly higher blood flow. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels, which was accompanied by a reduction in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of the PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. The frequency-response profile to electrical stimulation of the PAN shifted to the right in inflamed joints compared with normal joints, suggesting a reduction in the efficacy of the sympathetic nervous system in regulating blood flow to the inflamed joints. Although the inflamed joint had a higher blood flow, Ps,O2 was lower compared with the normal joint. The results of this study show significantly altered blood flow, Ps,O2 and nerve-mediated constrictor responses in the acutely inflamed joint. These are related to the inflammatory response and may contribute to the pathogenesis of arthritis. PMID- 7786512 TI - Composition and viscosity of interstitial fluid of rabbits. AB - Open-ended plastic tubes were used as capsules for obtaining interstitial fluid from rabbits. The capsule was a 2.5 cm long plastic tube with an inner diameter of 6 mm. Three small incisions were made in the dorsal mid-line of the anaesthetized rabbit; two capsules were inserted into each incision. A sample of capsular fluid was obtained 6 weeks later by inserting a hypodermic needle through the skin. The volume of fluid obtained from the capsule was sufficient for the analysis of total protein, albumin, albumin:globulin ratio, colloid osmotic pressure and the fluid viscosity. Despite the significantly lower total protein, albumin, globulin and colloid pressure of intracapsular fluid compared with plasma, the intracapsular fluid was found to have a greater viscosity. It is our opinion that the increased viscosity of the intracapsular fluid is due to the presence of a high molecular weight substance other than albumin and globulin, possibly hyaluronan. PMID- 7786514 TI - Influence of stretch on excitation threshold of single frog ventricular cells. AB - The excitation threshold of enzymatically dissociated single frog ventricular myocytes was measured as a function of cell length or sarcomere length. Field stimulation with 3 ms duration rectangular current pulses was applied via two platinum wire electrodes oriented either parallel or perpendicular to the long axis of the cell. Excitation threshold was measured as the amplitude of applied current, with an error of less than 1%. Single cells were held isometrically by two glass pipettes and wrapped around an optical fibre, which was used to control cell length. Sarcomere length was measured using video microscopy and a phase locked loop system. Changes in cell length and sarcomere length were induced by mechanical stretch and release of the whole cell. The excitation threshold decreased with increasing resting length (preload), and increased with decrease of the cell length back to its original length, regardless of the orientation of the electric field. The measured change in excitation threshold with stretch was of the order of 1%/% strain. These results suggest that stretch affects the excitation threshold of cardiac cells by factors other than simple shape changes in the cell, perhaps through the activity of mechanosensitive ionic channels. PMID- 7786515 TI - Recognition of a pharyngo-oesophageal sphincter inhibitory reflex in dogs and its role in deglutition. AB - The present study describes the 'pharyngo-oesophageal sphincter inhibitory reflex' and its clinical significance. The study was performed on twelve anaesthetized dogs. A balloon-tipped catheter was placed within the pharyngo oesophageal sphincter (POS) and another in the pharynx. The POS response to distension of the pharynx with a balloon filled with 2, 4 or 6 ml of water was recorded before and after application of local anaesthetic to the POS, and after successive section of the anatomical constituents of the POS. Upon pharyngeal distension, POS pressure was reduced; the greater the distension, the greater the pressure reduction. The anaesthetized POS did not respond to pharyngeal distension. Section of the cricopharyngeus muscle did not influence the resting POS pressure or the POS response to pharyngeal distension. The POS pressure dropped significantly (P < 0.0001) and was unresponsive to pharyngeal distension after section of both the cricopharyngeus muscle and the oesophageal circular muscle bundles. This shows that the cricopharyngeus muscle is not involved in the upper oesophagus sphincter mechanism. PMID- 7786516 TI - Depression of ventilation by dopamine in cats: effects of bilateral cervical sympathetic and vagal trunk section. AB - The contribution of sympathetic and vagal inputs to ventilatory depression induced by dopamine was studied in eighteen anaesthetized, spontaneously breathing, normoxic cats. Breathing was via a tracheostomy. Dopamine (20 micrograms (kg body wt)-1) was injected intravenously in the intact animal, then after section of the cervical sympathetic trunks, and finally after midcervical vagotomy. Dopamine, injected as a bolus, induced depression of ventilation, affecting predominantly the volume component of the breathing pattern at all experimental stages. The extent of volume reduction was larger and different from that in intact animals following section of sympathetic (P < 0.05) and vagal trunks (P < 0.01). The respiratory cycle was significantly prolonged (P < 0.01) prior to vagotomy, due entirely to the increase in the expiratory time (TE). Bilateral section of the carotid sinus nerves performed in six cats virtually abolished postdopamine ventilatory depression. PMID- 7786517 TI - Responses to reduced water intake, including dehydration natriuresis, in sheep excreting sodium predominantly in urine or in faeces. AB - Sheep which were predominantly urinary excretors (U) or faecal excretors (F) of sodium were exposed to a 75% reduction of water intake for 72 h. The experiment was performed on moderate, low or high sodium intakes (0.4, 0.05 or 1.2 mmol kg-1 day-1) to test the hypothesis that dehydration natriuresis was not a cause of sodium depletion but a defence against hypernatraemia. Dehydration caused elevation of plasma sodium concentration, osmolality, antidiuretic hormone (ADH) and oxytocin but, as in other experiments, a fall in haematocrit. The two higher levels of sodium intake were associated with dehydration natriuresis but also a smaller increase in faecal sodium excretion in both U and F sheep. On low sodium intake, however, neither urinary nor faecal sodium excretion increased in either group of sheep although the rise in plasma sodium concentration caused by dehydration was similar. Thus, when there is a risk of sodium depletion, due to low sodium intake, dehydration natriuresis does not occur, consistent with the hypothesis. Active sodium transport inhibitor (ASTI) and atrial natriuretic peptide (ANP) fell rather than rose during dehydration. Since aldosterone is suppressed by the higher levels of sodium intake, none of these hormones is likely to mediate dehydration natriuresis in sheep. F sheep showed more effective renal and faecal water conservation when dehydrated. During water restriction, the urinary potassium excretion of U sheep was significantly reduced, unlike that of F sheep; moreover, the latter maintained an identical plasma potassium concentration between baseline and restriction period, whereas in U sheep it was 0.3 mmol l-1 higher during water restriction. Increased drinking rather than reduced urine output was the basis of rehydration when ad lib. water intake was restored. PMID- 7786518 TI - Renal, endocrine and vascular effects of atrial natriuretic peptide in a novel vasopressin-deficient genetically hypertensive strain of rat. AB - In the absence of the potentially confounding influence of vasopressin in hypertension, the effects of atrial natriuretic peptide (ANP) on arterial blood pressure and renal handling of water and sodium were assessed from comparison of responses to intravenous ANP infusion in anaesthetized vasopressin-deficient New Zealand genetically hypertensive (DI/H) rats and their normotensive substrain (DI/N). After 320 min of hypotonic saline infusion, plasma ANP concentration was significantly higher in DI/H compared with DI/N rats. ANP administration increased circulating ANP concentration in both groups. Plasma angiotensin II concentration was higher in DI/H than in DI/N rats; infusion of ANP raised circulating angiotensin II in both groups though this achieved statistical significance only in DI/N rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and, in both, were reduced markedly by I.V. ANP infusion. Administration of ANP produced sustained hypotension in both groups. However, the hypotensive effect of ANP was more pronounced in DI/H compared with DI/N rats. Heart rate was initially similar in the two groups, and infusion of ANP produced no detectable change. By comparison with animals maintained on hormone-free infusate, urine flow increased markedly over the 80 min period of ANP infusion in both groups, by 142% in DI/H rats and 127% in DI/N rats. ANP administration produced a natriuresis in both groups but the increase in Na+ excretion was much greater in DI/H (342%) than in DI/N (139%) rats. It appears from the current study that vasopressin-deficient hypertensive rats are more sensitive to ANP with regard to effects on blood pressure and renal excretion than their vasopressin-deficient normotensive substrain. These differences may, in part, reflect adjustments to long-term elevation in blood pressure and in plasma ANP concentration in hypertension and, in part, rely on the associated disturbances in related endocrine systems. PMID- 7786519 TI - Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep. AB - An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289 treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses. PMID- 7786520 TI - The effects of attentional factors on an inhibitory jaw reflex in man. AB - Electromyographic recordings (EMGs) were made from the active masseter muscle, of the inhibitory reflex evoked by application of electrical stimuli to the skin of the upper lip in fifteen human subjects. In control sequences, the reflex had a mean latency of 42 +/- 1.1 ms and a mean duration of 45 +/- 2.1 ms. The magnitude of the reflex (measured by integration of the EMG) was reduced (by 18 +/- 7.0%, n = 11; P < 0.05, Student's t test) while the subjects concentrated on a visual feedback signal in order to maintain a steady level of EMG activity. It was further reduced (by 25 +/- 3.6%, n = 10; P < 0.001, Student's t test) when the subjects additionally undertook mental calculations (the 17-times table). These effects were predominantly in the later parts of the responses. They occurred regardless of whether the baseline activity in the masseter muscle was inadvertently raised or lowered during the conditioning procedures. It is concluded that attentional factors can modulate jaw reflexes in man by exerting an influence on the reflex pathway at a point prior to the motoneurones. The underlying mechanism may involve the activation of descending inhibitory pathways and/or a facilitation of mechanisms underlying excitatory responses in jaw closing muscles. PMID- 7786521 TI - Treatment of psoriasis with anthrones-chemical principles, biochemical aspects, and approaches to the design of novel derivatives. AB - Antipsoriatic anthrones are probably the most commonly used topical agents in the treatment of psoriasis. There is growing evidence that the biochemical basis for their mechanism of action at the molecular level is related to their redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical, and hydroxyl radical. These species are involved in a variety of oxidative effects affecting cellular targets that have been implicated both in the mode of action and the skin-irritating properties of antipsoriatic anthrones: interaction with DNA, inhibition of various enzyme systems associated with cell proliferation and inflammation, such as glucose-6 phosphate dehydrogenase and inflammation, such as glucose-6-phosphate dehydrogenase and 5-lipoxygenase, and destruction of membrane lipids. Furthermore, the application of this information to the design of novel derivatives is discussed. In particular, compounds with diminished oxygen radical generating properties have been developed, which may permit a separation of antipsoriatic and inflammatory effects. Some of the novel anthrone analogs which produced significantly less amounts of oxygen radicals than dithranol compared favorably in biological tests with this known antipsoriatic drug as an alternative method of treating psoriasis. PMID- 7786522 TI - Inhibitor of the release of mast cell mediators does not improve the psoriatic plaque. AB - The number of mast cells is increased in psoriatic lesions and this is particularly prominent in their early phase. Mediators released by mast cells may interfere with various aspects of cutaneous inflammation and epidermal proliferation. Therefore, the aim of the present investigation was to find out whether a 4-week treatment period with Tiacrilast, a highly potent inhibitor of mast cell degranulation, might have antipsoriatic potential. A total of 31 patients with plaque-type psoriasis were evaluated after treatment with a 3% Tiacrilast hydrogel and hydrogel alone, in a double-blind, placebo-controlled, within-patient comparative study. No statistically significant improvement of the Tiacrilast-treated plaques compared to the hydrogel-treated sites could be demonstrated. Therefore, the present study does not provide evidence of a potential role of mast cell degranulation in the treatment of psoriasis. PMID- 7786524 TI - Regulatory effects of antipsoriatic agents on interleukin-1 alpha production by human keratinocytes stimulated with gamma interferon in vitro. AB - It is known that keratinocytes produce and secrete interleukin-1 (IL-1) de novo and that this process can be enhanced by various stimulators. IL-1 has been shown to be a potent proinflammatory cytokine which mediates inflammation in various cutaneous disorders. It has also been demonstrated that gamma-interferon (IFN gamma) which is released from infiltrated T cells can be detected in inflamed lesional sites. In order to understand the effects of IFN-gamma on IL-1 production by keratinocytes in such inflammatory lesions, normal human keratinocytes (NHKs) and human squamous cell carcinoma cell line (HSC-1) cells were cultivated with recombinant human IFN-gamma (rIFN-gamma) and IL-1 levels were measured by ELISA. The effects of antipsoriatic agents such as hydrocortisone (HC), cyclosporin A (CsA), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogue MC903 on IL-1 production by keratinocytes were also investigated. IL-1 release by both NHK and HSC-1 cells was accelerated by stimulation with rIFN-gamma dose-dependently, although IL-1 alpha was released only transiently by rIFN-gamma-stimulated NHKs in serum-free keratinocyte growth medium containing HC. Antihuman IFN-gamma antibody inhibited IL-1 alpha release by HSC-1 cells stimulated with rIFN-gamma, suggesting that IL-1 alpha release from keratinocytes is upregulated by IFN-gamma. HC (5 micrograms/ml), 1,25(OH)2D3 (10(-6) M) and MC903 (10(-6) M), but not CsA (5 micrograms/ml), inhibited IL-1 alpha production by HSC-1 cells stimulated with 100 U/ml of rIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786525 TI - Use of human skin recombinants as an in vitro model for testing the irritation potential of cutaneous irritants. AB - Two human skin recombinants, the epidermis reconstructed on the deepidermized dermis (RE-DED) or on fibroblast-populated collagen matrix (Living Skin Equivalent, LSE), were used to study the irritating effect of sodium lauryl sulfate (SLS). The extent of cytotoxicity induced after a 24-hour exposure period to increasing concentrations of SLS (0-5%) was evaluated on the basis of (1) morphological perturbations, (2) changes in the expression of differentiation specific protein markers (keratin 1, 10, 6, 16, involucrin and transglutaminase), (3) cell membrane integrity (LDH leakage) and (4) release of proinflammatory mediators (PGE2, IL-1, IL-6 and IL-8). SLS induced significant changes in epidermal morphology and changes in the expression and localization of differentiation-specific protein markers when applied topically in concentrations higher than 1% on RE-DED and higher than 0.1% on LSE. The exposure of both human skin recombinants to SLS resulted in a dose-dependent release of LDH, PGE2 and IL 1 alpha and in an increase in keratinocyte intracellular IL-1 levels. Upon application of 5% SLS on RE-DED the total (intra- and extracellular) IL-1 levels remained high but due to cell damage the intracellular IL-1 level was markedly decreased and the extracellular IL-1 level increased. Similar observations have been made with LSE after application of 0.5% SLS. However, with LSE the extracellular IL-1 alpha levels were found to be about 100 times lower than those measured with RE-DED. Exposure of LSE to SLS induced a marked increase of IL-6 production in fibroblasts incorporated in the collagen matrix. Contrary to LSE, both intra- and extracellular levels of IL-6 were low in unexposed controls and were only marginally modulated by the exposure of the RE-DED to SLS. In addition, a dose-dependent increase in IL-8 release was observed upon application of SLS on RE-DED. The results of the present study indicate that concentrations of SLS required to induce epidermal irritancy in vitro approximate those inducing irritation in human skin in vivo. All parameters used in the present study for evaluation of toxicity can serve as useful endpoints for screening of contact skin irritancy in vitro. Compared to RE-DED, the LSE seems to be more susceptible to SLS. The differences in sensitivity between LSE and RE-DEd can be ascribed to reported differences in their stratum corneum barrier function. PMID- 7786523 TI - Differential utilization of linoleic and arachidonic acid by cultured human keratinocytes. AB - The essential fatty acid, linoleic acid (LA), is required for the epidermal barrier and LA is also the precursor fatty acid for arachidonic acid (AA). Both fatty acids are imported from systemic sources, because AA is also not synthesized in the epidermis. The present studies were undertaken to compare the uptake and incorporation into cellular lipid of these fatty acids and to determine whether they compete with one another in these processes in relation to keratinocyte differentiation. The incorporation of [14C]LA and/or [14C]AA into phospholipids and triglycerides was examined in keratinocytes cultured under submerged and lifted conditions. In submerged (less well-differentiated) cultures, more LA was incorporated into phospholipids than AA, while AA was incorporated into triglycerides to a greater extent. When given together, neither fatty acid influenced the total and/or relative uptake and lipid distribution of the other. Compared to submerged cultures, the uptake of LA increased 2-fold in lifted (differentiated) cultures, while the uptake of AA was unchanged. Lifting increased the proportion of AA incorporated into phospholipids, but did not alter the distribution of LA among phospholipids or triglycerides. These data suggest that the essential fatty acids, LA and AA, which are destined for different metabolic roles within the keratinocyte do not compete with one another during their uptake and distribution among cellular lipid species. Furthermore, as keratinocytes differentiate in culture, their increased requirement for LA for the synthesis of barrier lipids may be achieved through the preferentially enhanced uptake and lipid incorporation. PMID- 7786526 TI - Update in surgical treatment of acute post infarction VSDs and MIs. PMID- 7786527 TI - Modified operation technique for orthotopic heart transplantation. AB - Atrioventricular (AV) valve dysfunction with tricuspid regurgitation is a common finding after orthotopic heart transplantation (HTx). In 20 patients the heart transplantation was performed with bicaval anastomoses and the results were compared to the precedent 20 patients operated with the standard technique. The right atrium of the recipient was completely removed and the caval anastomoses were performed on the beating heart during reperfusion. Using an interrupted suture line, no stenoses at the venous anastomoses were seen as known from the early implantation technique in heart-lung transplantation. Due to a more stable sinus rhythm only 15% of the patients in the bicaval group needed prolonged pacing (> 30 min) versus 55% (P < 0.01) in the group with standard operation. One to 3 months after surgery the transthoracic echocardiographic evaluation of the AV valve function showed tricuspid valve regurgitation (TVR) in 20% of the patients with bicaval anastomoses versus 75% with a right atrial anastomosis (P < 0.001). Tricuspid valve regurgitation during the first 2 weeks (in 31% of recipients with bicaval and in 70% with atrial anastomoses) improved in all recipients with bicaval anastomoses and in 14% of the recipients with atrial anastomosis. The modification of the operation technique did not result in significantly longer bypass time (75 +/- 14 versus 68 +/- 14 min) and ischemia time (44 +/- 12 versus 41 +/- 9 min with local organ procurement and 111 +/- 24 versus 101 +/- 19 min with distant organ procurement). The AV valve function and the postoperative rhythm after orthotopic HTx can be improved by implanting the heart with bicaval anastomoses. PMID- 7786528 TI - Replacement of the ascending aorta and aortic arch with bovine pericardial grafts. A preliminary report. AB - Bovine pericardial (BP) grafts have been clinical use at Biocor Hospital since 1989 for replacement or repair of the ascending aorta (AsAo) and initial segment of the aortic arch (AoAr). The main advantages of BP grafts that have justified their clinical application are much easier surgical technique, perfect hemostasis and low cost. From Feb/89 to Feb/94, 88 BP grafts were implanted in the AsAo or the AoAr. There were 33 valved conduits, 47 non-valved conduits and 8 patches. The main indication for the procedure was acute dissection of the aorta, accounting for 50% of the cases. The total hospital mortality was 20.4%. Follow up was obtained in all but two patients. Patients who survived 2 or more years postoperatively (n = 31) underwent either an echocardiographic or an angiographic study in order to access the behavior of the graft, which was perfect in all of them. The current follow-up is short and complications such as calcification may still develop. However the present study has clearly shown the superior handling and better hemostasis of BP grafts compared to the classical Dacron prosthesis. PMID- 7786529 TI - Interrupted warm blood cardioplegia for coronary artery bypass grafting. AB - Continuous warm blood cardioplegia has been used with good clinical outcome in both antegrade and retrograde delivery. However, the continuous delivery of cardioplegia is sometimes interrupted for adequate visualization and flow is not constant with heart manipulation during operation. We studied the effects of interrupted antegrade delivery of warm blood cardioplegia on myocardial metabolism and clinical results after surgery. Fifty-five patients undergoing isolated coronary bypass surgery received warm blood cardioplegia (n = 29) or cold crystalloid cardioplegia (n = 26) in an antegrade fashion. During reperfusion, myocardial oxygen consumption, lactate extraction, creatinine kinase isoenzyme (CK-MB), and malondialdehyde (MDA) were measured. Post-operatively, serum CK-MB and cardiac output (CO) were determined over a period of time. Myocardial oxygen extraction in the warm group was significantly greater than in the cold group 1 min after reperfusion (P < 0.02). The results revealed a tendency for patients in the warm group to have prior lactate extraction, although the difference did not reach statistic difference (P < 0.10). After removal of the aortic cross-clamp, the heart returned to sinus rhythm spontaneously in 90% of the patients with warm cardioplegia and 15.4% of those with a cold heart (P < 0.01). Postoperatively, there was no significant CK-MB or MDA release in either group except for one patient with perioperative myocardial infarction. After operation inotropic support was required for two and one patient in the warm and cold groups, respectively, although there were significantly more patients with poor left ventricular function in the warm, than in the cold, group (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786530 TI - Delivery pressure of the cardioplegic solution influences myocardial protection. AB - To investigate whether cardioplegic solution (CS) delivery pressure influences myocardial protection, intermittent infusions of CS at different pressures were used in an isolated Langendorff rat heart preparation. In group 1 the hearts were kept arrested for 210 min at 12 degrees C with intermittent infusions of 5 ml CS every 20 min at 30 cm H2O (22 mmHg) pressure, in group 2 the same volume of CS was infused at 100 cm H2O (73.5 mmHg) pressure, in group 3 at 145 cm H2O (106.5 mmHg) pressure and in group 4 at 238 cm H2O (175 mmHg) pressure. There was a significantly higher coronary resistance in groups 1 and 4 (7.3 +/- 0.2 RU and 6.9 +/- 0.2 RU) than in groups 2 and 3 (4.2 +/- 0.2 RU and 4.2 +/- 0.2 RU) (P < 0.05) during the ischemic period. There were no significant differences between group 2 and 3 in the reperfusion period. Groups 2 and 3 showed higher coronary flow and left ventricle developed pressure than group 1 and 4. Hearts from group 1 and 4 had lower adenosine triphosphate (7.88 +/- 0.44 mumol.g-1, 5.56 +/- 0.56 mumol.g-1) (P < 0.05) and creatine phosphate (24.66 +/- 0.47 mumol.g-1, 15.34 +/- 0.94 mumol.g-1) (P < 0.05) content at the end of the reperfusion period than group 2 (10.56 +/- 0.41 mumol.g-1, 30.06 +/- 0.38 mumol.g-1) and group 3 (14.13 +/- 0.69 mumol.g-1, 35.25 +/- 0.78 mumol.g-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786531 TI - Comparison of propafenone to atenolol for the prophylaxis of postcardiotomy supraventricular tachyarrhythmias: a prospective trial. AB - To compare the efficacy of propafenone to atenolol in the prevention of supraventricular tachyarrhythmias (SVT) following cardiac surgery, 207 consecutive patients were randomly allocated to receive either propafenone 300 mg twice daily (105 patients) or atenolol 50 mg once daily (102 patients) orally for 7 days after operation. Double blinding was achieved using placebos. The end point was the development of a SVT which was symptomatic, recurrent, or lasting over 2 minutes, or the occurrence of adverse effects possibly attributable to the drugs. The groups were well matched for age, sex, bypass- and cross-clamp times, and other data. Thirteen patients in the propafenone group and 11 in the atenolol group developed SVT during the first week after operation. (P = 0.89, non significant, chi-squared with Yates' correction). In our study propafenone and atenolol were of approximately equal efficacy in preventing post cardiotomy SVT. Propafenone may have an advantage in being less negatively inotropic than atenolol; it could therefore be used in patients with poor left ventricular function or marginal haemodynamics when a beta blocker is contraindicated. PMID- 7786532 TI - Posterior pericardiotomy reduces the incidence of supra-ventricular arrhythmias following coronary artery bypass surgery. AB - A prospective study of 100 patients undergoing coronary artery bypass surgery was performed to demonstrate the effectiveness of a posterior pericardiotomy in reducing the incidence of pericardial effusions and, consequently, reducing the incidence of supraventricular arrhythmias in the post-operative period. Pericardial effusion occurred in 4 of 50 patients following a posterior pericardiotomy, whereas effusion occurred in 20 of 50 patients in whom a pericardiotomy was not created (P < 0.0005). Supra-ventricular arrhythmias occurred in 4 patients in the pericardiotomy group and 18 in the group treated without pericardiotomy (P < 0.005). No complications resulted from this procedure. We conclude that pericardiotomy is a simple, safe and effective method for reducing the incidence or pericardial effusion and thereby post-operative supra-ventricular arrhythmias. PMID- 7786533 TI - Incidence of deep and superficial sternal infection after open heart surgery. A ten years retrospective study from 1981 to 1991. AB - Between January 1981 and December 1991, 4137 adult patients underwent various cardiac procedures via a median sternotomy under cardiopulmonary bypass. The overall infection rate was 1.33%, including superficial wound infections (SWI) (1.18%) and deep sternal infection (DSI) (0.145%). Pericardial and retrosternal suction drains with a vent allowed a better drainage of blood and serosities and probably contributed to our low DSI rate. Eleven factors predisposing to infection were evaluated by Fisher's exact test. Only the operative urgency (P = 0.006), reexploration for bleeding (P = 0.00001) and preoperative renal failure (P = 0.0005) were statistically significant. Twenty of our infected patients had no risk factors for infection. When the risk factors described in the literature were applied to our infected patients, only one had no risk factor. PMID- 7786534 TI - Changes in gastric tissue oxygenation during mobilisation for oesophageal replacement. AB - We have measured changes in gastric tissue oxygen tension (PtO2, mmHg), with a modified Clark oxygen electrode, in eight patients (median age 59 years, range 52 to 74) undergoing oesophagectomy for carcinoma. Operations were performed with a cervical anastomosis and the stomach mobilised on the right gastric and gastroepiploic arteries. Tissue oxygen tension was measured in the gastric fundus at 4 points: (1) before mobilisation, (2) after mobilisation with the stomach in the abdomen, (3) with the fundus lifted to the neck and (4) after anastomosis. From a mean of 77 mmHg before mobilisation, PtO2 was halved to 36 mmHg after mobilisation with no further fall after transposition to the neck or anastomosis. Arterial oxygen concentration (PaO2), mean arterial pressure (MAP) and oxygen delivery (DO2) were similar at each point. Tissue oxygen tension was correlated with PAO2 at points 1 and 4 but MAP only at point 1 and DO2 not at all. These findings document the relationship of gastric PtO2 to mobilisation of the stomach and demonstrate the important influence of PaO2 on PtO2. PMID- 7786535 TI - Descending necrotising mediastinitis: a case report and review of the literature. AB - We report a case of descending necrotising mediastinitis complicating an oropharyngeal infection in a 25-year-old male. The clinical presentation, the diagnosis and the management of this rare disease and its complications are discussed in this case report with a brief review of the literature. PMID- 7786536 TI - Pyoderma gangrenosum as a complication of coronary artery bypass grafting. AB - A 60-year-old male patient developed progressive wound ulcerations, simulating wound sepsis after coronary bypass operation. The condition did not respond to intensive antibiotic therapy. Based on clinical signs and biopsy, the diagnosis of pyoderma gangrenosum was made and successfully treated with cyclosporin A. Pyoderma gangrenosum, although extremely rare, must be considered as a possible diagnosis in wound complications unresponsive to traditional therapy. PMID- 7786538 TI - Isolated right ventricular unloading for postcardiotomy right ventricular failure in a child. AB - Severe right ventricular (RV) failure after total correction of double outlet RV (DORV) with pulmonary atresia was completely reversed with extracorporeal mechanical RV unloading in a 2.5-year-old child. The patient could be weaned after 168 h of RV assist device (RVAD) support using a centrifugal Bio-Medicus pump and was discharged from the hospital without adverse effects. This experience of isolated RV unloading in a child encourages further application of RVAD in pediatric patients. PMID- 7786540 TI - [Preparation of a levodopa/carbidopa solution in ascorbic acid (citridopa) and chromatographic and electrochemical assessment of its stability over 24 hours]. AB - Levodopa/inhibitor improves motor function in parkinsonian patients. In its usual tablet form, however, its efficacy is reduced after several years, partially due to absorption deficiencies and changes in plasma kinetics; thus, other therapeutic strategies to provide a stable, easy to prepare formula are being sought. One such approach could be to dissolve L-dopa/carbidopa in ascorbic acid. This report describes the preparation method and demonstrates the stability of the sample using High pressure liquid cromatography (HPLC) with electrochemical detection. Regardless of the number of tablets the patient takes, the concentration of L-dopa/carbidopa/ascorbic acid remains constant (1/0.25/2 mg/ml). Thus, a patient taking 5 tablets of Sinemet Plus a day, would pulverize them in a glass, ceramic or marble mortar and add them to a measuring cup containing a 1 gram tablet of vitamin C (Redoxon) dissolved in 500 cc of cold water. This would be shaken or stirred until the Sinemet powder had dissolved. A few particles remaining in suspension after this process would be of no concern. The liquid would be stored in the refrigerator in an opaque or aluminum foil covered glass bottle or, if possible, in several small dose-size vials. Using a measuring cup, a test tube and a syringe, the correct volume can be drawn out of the bottle and shaken well before drinking. The solution would be taken at regular intervals throughout the day (which vary from one patient to another) to maintain stable plasma L-dopa levels. PMID- 7786539 TI - Early degeneration of a Medtronic intact bioprosthesis in aortic position. PMID- 7786541 TI - [Classification of head injuries based on computerized tomography: prognostic value]. AB - A new classification system for head injury based on the findings of computerized tomography was used in a population of 809 head injured patients. The system emphasizes the status of mesencephalic cisterns, the degree of midline shift and the presence or absence of mass lesions, allowing high risk patients to be identified and outcome to be predicted. PMID- 7786537 TI - Congenital pulmonary arteriovenous fistula. AB - Pulmonary arteriovenous fistula wherein the malformation has venous drainage directly to the left atrium is a rare anomaly. Two case reports present such unusual arteriovenous malformations successfully treated by surgery. PMID- 7786542 TI - [Lobar dementia]. PMID- 7786543 TI - [Hemidiaphragmatic paralysis as a manifestation of familial brachial plexus neuropathy]. AB - We present a patient with familial brachial plexus neuropathy (FBPN) who is in the second generation of a family found to have this disease. The patient suffered phrenic paralysis, which has only been previously described in association with FBPN in 4 similar cases, all of which also involved the left phrenic nerve. The side of phrenic paralysis's was unrelated to the side where brachial plexus lesions occurred. We believe that paralysis of the diaphragm, although rare, can be considered a sign of FBPN and that therefore this disease should be included in the differential diagnosis of such paralysis. This is particularly so whenever family or personal history suggest that the peripheral nervous system may be involved, compromising the brachial plexus, or whenever facial or digital dysmorphia is present. PMID- 7786544 TI - [Multiple entrapments neuropathy in adult polyglucosan body disease]. AB - Adult polyglucosan body disease (APBD) is a rare condition characterized by neuropathy, dementia, upper motor neuron dysfunction and neurogenic bladder. For diagnosis, the presence of polyglucosan bodies (PB), or PAS (+) glucose polymers, must be demonstrated. In this description of a woman with APBD and multiple entrapment neuropathy, we discuss a possible role for morphological changes induced by PB in increasing susceptibility to pressure palsies. PMID- 7786545 TI - [Palilalia due to thalamic infarctions]. AB - A 45-years-old woman developed palilalia without other neurologic symptoms or signs. Cranial MR and CT scan showed only bilateral thalamic infarcts; the SPECT showed bilateral frontoparietal hypoactivity. We conclude that involvement of the supplementary motor area by diaschisis after bilateral thalamic lesions may produce palilalia. PMID- 7786546 TI - [Spontaneous syncope as the only sign of Arnold-Chiari type I malformations]. AB - We present a patient suffering from spontaneous recurrent syncopes as the sole symptom of Arnold-Chiari type I malformation. The syncopes were attributed to transient compression of neural and/or vascular structures at the cranio-cervical junction by the descended cerebellar tonsils, triggered by an increase in intracranial pressure. The disappearance of symptoms after posterior fossa decompression confirmed our hypothesis. PMID- 7786548 TI - [Acute myelopathy, anti-phospholipid antibodies and S-protein deficiency]. PMID- 7786549 TI - [Neurology in primary health care]. PMID- 7786547 TI - [Peripheral neuropathy in progressive systemic sclerosis]. AB - We report a patient that developed a sensorimotor polyneuropathy more than a year before the appearance of the typical clinical signs of progressive systemic sclerosis. A sural nerve biopsy showed epineural vasculitis with involvement of the basal membrane of the endoneural vessels, without proliferation of the connective tissue. PMID- 7786550 TI - [Neurology in primary health care]. PMID- 7786551 TI - [Remarks on Ross syndrome]. PMID- 7786552 TI - [Remarks on Ross syndrome]. PMID- 7786553 TI - [Information]. PMID- 7786554 TI - Sex education in schools: opportunities. PMID- 7786556 TI - Tokyo Citizens' Council for Health Promotion, and its action plan. PMID- 7786555 TI - An estimate of the prevalence of drug misuse in Liverpool and a spatial analysis of known addiction. AB - BACKGROUND: The objective of this study was to determine the prevalence and distribution of opiate and cocaine misuse in the City of Liverpool in 1991. The databases included residents of the city using opiates or cocaine, who were known to the Drug Dependency Units or the Infectious Diseases Unit, or who were arrested for possession of drugs in 1991. METHODS: A three-sample log-linear capture-recapture method was applied to databases containing details of drug users with City of Liverpool postcodes, to determine the prevalence of drug misuse in 1991. Linear regression analysis was performed to correlate the prevalence of known drug misuse with indices of material deprivation in each electoral ward. RESULTS: Data on 1427 individuals were analysed, producing an estimate of the drug-using population of 2344 [95 per cent confidence interval (CI) = 1972-2716] and a period prevalence of 5.2 per 1000 [95 per cent CI = (4.5 6.0) per 1000]. In the 15-29 year age group, the prevalence of drug abuse was 16.9 per 1000 [95 per cent CI = (13.9-19.9) per 1000]. There was a negative interdependence between the police and Drug Dependency Unit databases with attenders at the Unit being 7.2 (95 per cent CI = 4.6-11.4) times less likely to be arrested for possession than non-attenders. There was a strong correlation between the distribution of known drug use and material deprivation, as measured by the Townsend index (r = 0.75; p < 0.001). CONCLUSIONS: The capture-recapture method allows the prevalence of drug misuse to be estimated and provides more meaningful information than is available from the notification system. The study suggests that people in contact with drug services are less likely to commit crimes of possession of class A drugs than those not in contact with drug services. There is a strong association between drug abuse and deprivation, and therefore the purchasing of services for drug misusers should be focused on areas of deprivation. PMID- 7786557 TI - Quarterly communicable disease review July to September 1994. From the PHLS Communicable Disease Surveillance Centre. PMID- 7786558 TI - The ethnic health bibliography. PMID- 7786559 TI - Fractured neck of femur patients. PMID- 7786560 TI - Uptake of breast screening by Asian women. PMID- 7786561 TI - Environmental health in Australia. PMID- 7786562 TI - Safety and place of birth in Scotland. AB - BACKGROUND: The recent publication of policies suggesting women should have choice about where they give birth prompted a comparison of stillbirth and neonatal mortality rates for three types of maternity unit in relation to changes in booking and place of delivery. METHODS: Scottish Maternity Discharge records and data from stillbirth and neonatal death reports for Scotland were used to analyse stillbirth and neonatal mortality rates according to the level of care, birthweight and cause of death for the years 1986-1990. RESULTS: For those categories of stillbirths and neonatal deaths which are amenable to prevention by perinatal care, intrapartum stillbirth rates were higher in general practitioner (GP) units than in consultant units, but these accounted for only 11 stillbirths and the difference is compatible with chance variation. Neonatal mortality among babies weighting 2500 g or more was independent of type of hospital. Among babies weighing under 1500 g or 1500-2499 g, neonatal mortality was significantly higher in non-teaching hospitals than in teaching hospitals. CONCLUSIONS: Although the differences are compatible with chance variation, there is some suggestion that small GP hospitals might have higher rates of intrapartum stillbirths and such rates should be monitored. Provided that there are no barriers to transfer to hospitals with consultant units when appropriate, there is no evidence that these small GP hospitals are unsafe. The high neonatal mortality rates, especially among babies weighing 1500-2499 g in non-teaching consultant units, compared with teaching units, should be investigated further. PMID- 7786564 TI - Whither the NHS? PMID- 7786563 TI - Differences in hospital casemix, and the relationship between casemix and hospital costs. AB - BACKGROUND: The aim of the study was to examine the relationship between hospital costs and casemix, and after adjustment for casemix differences, between cost and institutional size, number of specialties, occupancy and teaching status. METHODS: A retrospective analysis of all admissions to nine acute-care NHS hospitals in the Oxford region during the 1991-1992 financial year was undertaken. All episodes were assigned to a diagnosis-related group (DRG) and a cost weight assigned accordingly. Costs per finished consultant episode, before and after adjustment for casemix differences, were analysed at the hospital and specialty level. RESULTS: Casemix differences were significant, and accounted for approximately 77 per cent of the difference in costs between providers. Costs per casemix-adjusted episode were not significantly associated with differences in hospital size, scope, occupancy levels or teaching status, but sample size was insufficient to investigate these relationships adequately. Specialty costs were poorly correlated with specialty casemix. This was probably due to poor apportionment of specialty costs in hospital accounting returns. CONCLUSIONS: Casemix differences need to be taken into account when comparing providers for the purposes of contracting, as unadjusted unit costs may be misleading. Although the methods used may currently be applied to most NHS hospitals, widespread use would be greatly facilitated by the development of indigenous cost weights and better routine hospital data coding and collection. PMID- 7786565 TI - Increasing response rates in telephone surveys: a randomized trial. AB - BACKGROUND: Sampling frames and mode of contact and administration of questionnaires are important factors contributing to response rates and selection bias in population-based research. The purpose of this paper is to evaluate whether contact by mail before contact by telephone increases response rate, and to assess the concurrent validity of telephone surveys for collecting health research and service data. METHODS: Two thousand households were randomly selected from electronic white pages. Half were randomly allocated to receive or not to receive an explanatory letter before telephone contact. Interviewers were blinded to whether a household received a letter. Respondents aged 18 years or over were randomly selected from within each household using a Kish grid and interviewed by telephone. RESULTS: The overall response rate was 68 per cent [confidence interval (CI) 66-70]. The response rate of those who received the letter was 76 per cent (CI 73-79), and of those who did not receive the letter was 60 per cent (CI 56-63). Use of the Kish grid to select randomly a respondent decreased the response rate by less than 10 per cent. The internal validity of the data was as follows: in a 10 per cent sub-sample, the Kish grid had been correctly applied in 93 per cent of households, and in 99 per cent of households the exclusion criteria had been correctly adhered to. The external validity was as follows: comparisons with data obtained from the same reference population using similar instruments administered face-to-face revealed no meaningful or significant differences in population estimates. CONCLUSIONS: Mail-out before telephone contact greatly increases response rates at low cost. Telephone surveys can yield valid, useful data for health research and service evaluation. PMID- 7786567 TI - Measuring health status with the SF-36: the need for regional norms. AB - BACKGROUND: Normative data on SF-36 scores in populations from Oxford and Aberdeen have recently been published. It has been suggested that such data provide suitable normative values for the UK population. However, other indices of health vary considerably across regions, and tend to be worse in areas such as South Wales. The objective of this study was to determine whether population SF 36 scores in West Glamorgan differ from scores from other parts of the United Kingdom. METHOD: The SF-36 health status questionnaire was administered to two random samples of adults aged 20-89 years, drawn from the West Glamorgan Family Health Services Authority register. One sample (n = 919) received postal questionnaires and those in the other sample (n = 1201) were interviewed in their own homes. Normative data from this study were compared with published data from other areas of the United Kingdom. RESULTS: SF-36 population scores were significantly lower in the two West Glamorgan samples; this was not due to differences in age, sex, social class, or response rates. CONCLUSION: Health status in West Glamorgan, as measured by the SF-36, is lower than in Oxford or Aberdeen. A national study would be required to provide appropriate normative data for the UK population. PMID- 7786566 TI - Does routine child health surveillance reach children most at risk of accidental injury? AB - BACKGROUND: There is currently an increasing emphasis on accident prevention as part of routine child health surveillance, which unlike opportunistic accident prevention has the potential to reach the whole population. However, non attenders at routine child health surveillance may also be children at higher risk of accidental injury, as there is some evidence that non-attenders may be more likely to live in socio-economic disadvantage, which is a risk factor for accidental injury. METHODS: A case control study was carried out in one general practice in Nottingham with 253 cases and 243 controls, aged four years and under, obtained from the practice age-sex register. Cases were defined as children who had attended the accident and emergency department, the general practitioner or the practice nurse after an accidental injury at any time during their life. Controls were children who had not had a medically attended accidental injury. Attendance at routine child health surveillance, before the date of the case's accidental injury, was assessed by attendance at the eight month hearing test, immunization status, child health clinic visits and home visits by the health visitor. RESULTS: There was no significant difference between cases and controls in attendance for the hearing test, or immunization status. Cases received significantly more home visits after adjusting for confounding variables (odds ratio 2.44, 95 per cent confidence intervals 1.28 4.66). CONCLUSIONS: These findings suggest that non-attenders at routine child health surveillance activities are not at an increased risk of medically attended accidental injury. They also suggest that health visitors can identify those children most at risk of accidental injury using criteria for classifying priorities in caseloads. PMID- 7786568 TI - The changing pattern of in-patient care. AB - BACKGROUND: A nationally representative longitudinal study presented the opportunity to describe National Health Service (NHS) and private in-patient care used over seven years by a population of young adults in relation to known risk factors for admission and for future health. METHODS: Information on each hospital admission between ages 36 and 43 years, comprising length of admission and whether under NHS or private care, was collected from 1625 men and 1623 women, the population of the 1946 birth cohort study. Obstetric care was excluded from most analyses. RESULTS: From this population, 22 per cent of men and 39 per cent of women were admitted to hospital at least once during the seven-year period, for a total of 11,276 days, a mean of 3.5 days (SD 13.1) for each person in the study, and 11.6 (SD 21.9) days for those admitted. The proportion of admissions not under NHS care rose from 14 per cent of all admissions in 1982 to 23 per cent in 1989. Employers contributed to health insurance for 25 per cent of employed men and 7 per cent of employed women. Risk of admission was greater, and admissions were longer, in those least educated and from poorest circumstances; men with largest waist-hip ratios were admitted for longer than others. Private admissions were proportionately greater in nonmanual classes and among those from favourable social and educational backgrounds, that is, those known to be at least risk of serious and chronic illness. CONCLUSION: Heaviest users of in patient care were those most likely to be at greatest health risk, who were least likely to have private health insurance. The rising mid-life uptake of private health insurance through employers (25 per cent of employed men by age 43 years) may foreshadow a future problem in a return to NHS care on retirement in this population, which represents the beginning of the future population bulge in the elderly. PMID- 7786569 TI - The detection and management of hypertension in the elderly of Northamptonshire. AB - BACKGROUND: The aim of this study was to apply recommendations from randomized controlled trials and guidelines on the detection and control of hypertension in the elderly to a district health authority population. METHODS: A cross-sectional audit of Northamptonshire general practitioners' (GPs') records from February to June 1993 was carried out. RESULTS: A total of 2428 notes of men and women aged 65 or over registered with their GP was audited. A large proportion of patients, 86 per cent (95 per cent CI 84.6-87.4 per cent), had a blood pressure record taken in the last 10 years. Of those with raised blood pressure (BP > or = 160/90 mmHg) 49 per cent (95 per cent CI 46.2-51.8 per cent) were untreated, and 58 per cent (95 per cent CI 54-61.9 per cent) of those labelled as hypertensive were not adequately controlled. The prevalence of labelled hypertension was 25 per cent (95 per cent CI 23.3-26.7 per cent). CONCLUSIONS: From these results it is estimated that between 11 and 29 fatal and non-fatal strokes could be prevented in the 65-74-year-old age population of Northamptonshire each year if current guidelines were followed. Improved detection and management of elderly hypertensive patients in primary care could contribute significantly towards the target for stroke reduction set in the Health of the nation strategy. PMID- 7786570 TI - The state of primary medical care in Bulgaria. AB - This paper describes the state of primary medical care in Bulgaria and related issues. This component of the state health system is based on the so-called principle of the 'district physician'. It is built on the idea of establishing long-lasting contact between the physician and the patients. Primary care is provided by a district therapist (for populations of up to 3000 inhabitants), a paediatrician (for 800-1200 children aged up to 14 years) and an obstetrician gynaecologist (for 16,000-18,000 female inhabitants), as well as by numerous freely accessible narrow-profile specialists. The main disadvantages of the existing system of primary medical care are the lack of opportunity for personal choice of physician, division of responsibilities among numerous physicians and other medical staff, expensive medical care owing to abundant polyclinical specialists, reduced physician's motivation and hampered users' influence on the quality of medical care. Questions about the future status of polyclinics and both children's and female health centres, as well as about the optimal ratio between family physicians and specialists, remain unresolved. PMID- 7786571 TI - Access to elective surgery at electoral ward level: the impact of the private sector. AB - BACKGROUND: Purchasers of health care receive no routine information on the use of the private health sector by their residents, and are consequently unaware of any resulting differentials in access to health services. This information would assist in assessing need for services on a locality basis. METHODS: For the period 1990-1992 surgical activity data from the single private hospital in Preston were examined by electoral ward of residence and compared with corresponding NHS data. RESULTS: For the procedures examined, the private sector contributed only 8 per cent to overall surgical activity within Preston. People from the more affluent wards were far more likely to use the private sector than those from deprived wards. CONCLUSION: The private sector did not introduce any inequity of access to surgery within Preston at electoral ward level. However, in districts with higher levels of private sector activity significant differentials in access may exist. PMID- 7786572 TI - An investigation into the default rate at the Fife colposcopy clinic: implications for target setting. AB - BACKGROUND: High default rates have been reported from the Fife colposcopy clinic in recent years. However, it was felt that this rate was misleading, as many patients who defaulted initially attended subsequent appointments. It was therefore decided to determine the default rate of a cohort of new patients given appointments at the clinic. The objective of the study was to determine the attendance rates for these new patients, between the dates they were first invited to their various appointments and the dates that their notes were subsequently examined as part of this study in September 1992. METHODS: A retrospective cohort study of new patients invited to the Fife colposcopy clinic was undertaken. The notes of 200 new patients who had been invited during the eight-month period January-August 1991 were selected by systematic sampling. The dates that they had attended for their new patient assessment/treatment, first follow-up and second follow-up appointments were recorded. Attendance rates were then calculated using an incomplete life-table method. Patients were censored if they failed to attend their assessment/treatment or review appointments by 1 October 1992. RESULTS: The study demonstrated that 96 per cent of patients attended their first treatment appointment within six months of their appointment date, 91 per cent of first review patients attended within six months, and 88 per cent of second review patients attended within four months. CONCLUSIONS: These findings suggest that there are two distinct groups of defaulters: those who default initially but subsequently re-attend, and those who default completely. We have named these type A and type B defaulters, respectively. This means that attendance within a certain period of time should also be used to monitor clinic attendance in addition to simple mean attendance rates. As patients who default completely may be more likely to have a severe histological lesion, further work is required to identify factors associated with this type of patient. PMID- 7786573 TI - Press coverage of the Cleveland child sexual abuse enquiry: a source of public enlightenment? AB - BACKGROUND: The objective of this study was to assess national and local newspaper reporting of events considered by a Public Enquiry which investigated a major crisis involving child protection services. The Judicial Enquiry, held in Cleveland, North East England, examined the actions of statutory bodies and the professionals working within them following the diagnosis of suspected sexual abuse in 121 children. METHODS: This is a descriptive study using analysis of legal transcripts and newspaper reports. The data involved a total of 216,360 lines of transcript evidence given by 111 witnesses and lawyers representing them at the Judicial Enquiry which lasted 74 days; together with 344,899 words in reports covering 17 newspapers (seven local and ten national). The main outcome measures were based on the volume and type of newspaper coverage including that for each witness' and lawyer's evidence. A coverage index related the amount of newspaper reporting to the extent of evidence given. RESULTS: The highest coverage of any single day of the Enquiry in both local and national newspapers occurred when Dr Marietta Higgs (one of the two principal paediatricians involved) made her first appearance. However, the highest interest (coverage index) was shown in evidence given by lawyers for the parents and the least in evidence given by public bodies. The evidence of witnesses was used very selectively by the press in emotive headlines to imply blame or support for the main protagonists or their actions. This sustained several lines of reporting: criticism of the doctors and social workers, inter-professional conflicts, damage and wrong-doing to the families and the search for someone to blame. CONCLUSIONS: The Cleveland crisis occupied newspaper headlines in the United Kingdom for more than a year. Much of the newspaper coverage took an adversarial approach which sought to apportion blame and take sides. The press appeared to report negative issues which were newsworthy and did not give a balanced view. Broader policy issues, which formed an important part of the Enquiry report's influence on subsequent child protection legislation, were largely ignored. PMID- 7786574 TI - Understanding variations in lengths of stay between hospitals for fractured neck of femur patients and the potential consequences of reduced stay targets. AB - BACKGROUND: Economic incentives exist to scrutinize length of stay variations between hospitals. However, the reasons for variations can be complex, and without knowing these the feasibility of shorter stay targets, and their implications for patient outcome, are unclear. METHODS: This research compared care received by patients admitted for fractured neck of femur at an inner-city university teaching hospital, an inner-city associated teaching hospital and an associated teaching hospital in an urban setting. Multiple regression and descriptive analysis were used to examine how in-patient acute stay was affected by the severity of cases on admission and the supply of beds beyond the acute setting. Data on patient outcome were mortality up to three months post fracture and functional ability at in-patient discharge and three months post fracture. RESULTS: A total of 492 patients were recruited. Patient outcomes at three months were similar at the hospitals. Multiple regression revealed significant differences between the patient stay of the inner-city teaching hospital and the urban associated teaching hospital. A difference in stay of around 14 days was demonstrated, with the urban hospital having the shorter stay. These differences were linked it to having a greater supply of non-acute beds. CONCLUSION: Significant differences in patient stay between hospitals can be due to factors beyond the direct control of the acute unit. Economic incentives may mean that purchasers and providers ignore a full analysis of these factors and set length of stay targets which are not feasible in the short term. This could reduce the quality and impair the outcome of patient care. PMID- 7786576 TI - Health services research in the United Kingdom 1990-1992. AB - BACKGROUND: Shortly before the National Health Service (NHS) research and development (R&D) strategy was launched in April 1991, the Department of Health commissioned a study to collect information on current health services research and related work in the United Kingdom. The term 'health services research' was interpreted as research that could usefully inform the contracting arrangements in the reformed NHS. METHODS: The information was collected from funding agencies, in particular the UK health departments, the Medical Research Council and medical research charities; academic departments and research units and centres; NHS authorities; and research registers and directories. A total of 6185 projects that were either in progress or completed between January 1990 and mid 1992 were identified. RESULTS: Forty-three per cent of projects were disease related; 33 per cent assessed health technologies. Patterns were evident in the database. Sixty-three per cent of the projects on diseases were covered by five categories: cancer, the largest category with a quarter of the disease projects; perinatal medicine; cardiovascular disease and stroke; HIV and AIDS; and mental illness. Conditions that cause severe discomfort but are not life threatening were poorly represented. Clinical trials formed 25 per cent of the health technology projects, but only 6 per cent of the trials assessed surgical procedures. Less than 10 per cent of all health technology projects contained a costing component. In England, 34 per cent of projects with identified funding sources were supported by medical charities and other independent bodies, 31 per cent by NHS authorities, 20 per cent by the Department of Health and 15 per cent by the research councils. CONCLUSION: This collection of information represents a 'snapshot' of the scope of health services research against which it will be possible to measure the changes promoted by the NHS R&D programme. PMID- 7786575 TI - Is a policy of cervical screening for all women attending a genito-urinary medicine clinic justified? AB - BACKGROUND: The study took place at the Genito-Urinary Medicine Department at the University Hospital of South Manchester and the Cytology Department at Christie NHS Trust Hospital. There were two main objectives, as follows: (1) to determine if patients attending a Genito-Urinary Medicine (GUM) Clinic are less likely to have had a cervical smear in the preceding five years than a control group drawn from the general population; (2) to compare the prevalence of cytological abnormalitity in cases and controls. METHODS: Cases comprised all women attending the Withington GUM Clinic, between 1991 and 1993, who had had a cervical smear taken at this clinic. Controls were selected from residents of the North West Regional Health Authority who had a cervical smear taken either by a general practitioner (GP) or in an NHS Community Clinic during the same period. The design was a matched case-control study. The main outcome measures considered the proportion of women who had had a cervical smear taken by a GP or in an NHS Community Clinic during the five years preceding the index smear, and the prevalence of abnormal smears in cases and controls. RESULTS: There was no significant difference in the screening history of cases and controls; 363 (50.2 per cent) cases had had a cervical smear taken in the preceding five years as compared with 380 (52.6 per cent) controls [chi 2 (1df) = 0.95; p > 0.05; 95 per cent confidence interval (CI) on difference in proportions, -7.1 per cent to 2.4 per cent]. There was a small case-control difference of borderline significance in the prevalence of all grades of cytological abnormality: 22.7 per cent of cases had abnormal cytology as compared with 18.5 per cent of controls [chi 2 (1df) = 3.98; 0.01 < p < 0.05; 95 per cent CI on difference in proportions, 1 per cent to 8.2 per cent). This excess was largely attributable to differences in the prevalence of minor cytological abnormality. There was no significant difference in the prevalence of cytological abnormality in those case-control pairs who had had a smear in the preceding five years. CONCLUSION: A policy of cervical screening of all GUM patients can no longer be sustained. We would recommend cervical cytology only for those women who have not been screened in the previous three to five years. PMID- 7786577 TI - The autumn peak in campylobacter gastro-enteritis. Are the risk factors the same for travel- and UK-acquired campylobacter infections? AB - BACKGROUND: In the autumn of 1992 there was an excess of campylobacter cases in Nottingham compared with the national average. No relative increase was seen for salmonella infections. METHODS: A case-control study with a postal questionnaire was carried out to determine exposure to possible risk factors. The patients were 282 laboratory confirmed cases of campylobacter and 318 culture negative controls who had submitted a faeces specimen. All patients were aged 18 or older. The main outcome measures were relative risks for campylobacter infection compared with controls with a negative faeces culture. RESULTS: Twenty-five per cent of cases were associated with foreign travel. Eating chicken and handling raw poultry were the main risk factors for UK-acquired infections. The number of cases with a history of contact with puppies or drinking milk that was either unpasteurized or from bottles with bird-damaged tops was small. CONCLUSION: Eating chicken and handling raw poultry are the main risk factors for campylobacter infections. Contact with puppies or drinking potentially infected milk can explain only a small percentage of campylobacter infections. Risk factors for infection acquired abroad follow a different pattern compared with UK-acquired cases. PMID- 7786578 TI - The inhibitory activity of an HIV type 1 peptide correlates with its ability to interact with a leucine zipper structure. PMID- 7786579 TI - Human immunodeficiency virus type 1-neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus. AB - An oligonucleotide encoding the amino acids 731-752 of the gp41 envelope protein of the human immunodeficiency virus type 1 strain IIIB, which is known to induce cross-reactive neutralizing antibodies in humans, was inserted into a full-length clone of the RNA encoding the coat proteins of cowpea mosaic virus (RNA 2 of CPMV). When transfected together with RNA 1 of CPMV, transcribed RNA 2 was able to replicate in plants and form infectious virions (CPMV-HIV). Purified virions were injected subcutaneously with alum adjuvant into adult C57/BL6 mice to determine their ability to stimulate ELISA and neutralizing antibody specific for HIV-1. Antisera to CPMV-HIV obtained after only two injections gave a strong ELISA response (mean of 1:25,800) using the free gp41 peptide as antigen, showing that the gp41 peptide incorporated into the chimera was immunogenic. The same antisera gave 97% neutralization of HIV-1 IIIB at 1:100 dilution, with a highly uniform response in all (six of six) animals tested. A third injection barely increased the neutralization titer. Normal mouse serum had no neutralizing activity. Antisera also strongly neutralized the HIV-1 strains RF and SF2. ELISA and neutralizing activity to HIV-1 IIIB declined after the second injection and were undetectable after 7 weeks, but were restimulated to the same level after the third injection. Neutralization was marginally more stable after the third injection. Antibody specific for CPMV epitopes was equally short lived. A bonus of this system was unexpected neutralizing activity specifically stimulated by unmodified CPMV virions, although this amounted to no more than 10% of the neutralizing activity stimulated by the CPMV-HIV chimera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786580 TI - Increase in sensitivity to soluble CD4 by primary HIV type 1 isolates after passage through C8166 cells: association with sequence differences in the first constant (C1) region of glycoprotein 120. AB - Primary isolates of human immunodeficiency virus type 1 (HIV-1) were obtained by coculture of peripheral blood lymphocytes (PBLs) from HIV-1-infected people with PBLs from uninfected donors. These viral stocks tend to be resistant to neutralization/inactivation by soluble CD4 (sCD4). When these stocks were passed through the T cell line C8166, virus stocks emerged that were sensitive to sCD4. Pre- and post-C8166 stocks maintained their sCD4-resistant and -sensitive phenotypes, respectively, with further passage in PBLs. Pre- and post-C8166 stocks were biologically cloned by two cycles of limiting dilution. The majority (14 of 17) of pre-C8166 clones were sCD4 resistant, and, conversely, the majority of post-C8166 clones (11 of 12) were sensitive to sCD4. Nucleotide and predicted amino acid sequence analysis in the env (gp120) region revealed a limited number of differences between the clones. The only differences that sorted with biological phenotype were in the first constant (C1) region of gp120. Adaptation to growth in C8166 cells and conversion from the sCD4-resistant to the sCD4 sensitive phenotype represent the emergence to prominence of viral species in the pre-C8166 stock that have a replication advantage in C8166 coincident with increased sensitivity to sCD4. PMID- 7786581 TI - Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AB - Quantification of HIV-1 RNA in human plasma has provided unique insight into AIDS pathogenesis and promises to hasten progress in antiretroviral therapy and vaccine research. However, no generally available HIV-1 RNA assay has yet been subjected to rigorous clinical testing or to comparative evaluation with research based RNA assays using large numbers of well-characterized clinical specimens. In this study, the Chiron Quantiplex branched DNA (bDNA) signal amplification assay was used to measure viral RNA in the plasma of 152 HIV-1-positive individuals at all stages of infection and in 12 patients before and after initiating zidovudine therapy. Eighty-six percent of patients had bDNA assay results above the 10,000 RNA Eq/ml sensitivity cutoff. Branched DNA values were significantly correlated with plasma viral RNA levels determined by quantitative competitive polymerase chain reaction (QC-PCR) assay (Spearman rank correlation, r = 0.89), infectious plasma virus titers (r = 0.72), p24 antigen levels (r = 0.51), immune complex dissociated p24 antigen levels (r = 0.56), and CD4+ lymphocyte counts (r = -0.72; p < 0.0001 for all comparisons). Plasma viral RNA determinations by bDNA and QC PCR assays were quantitatively similar in the range of 10(4) to 10(7) RNA molecules/ml [log bDNA = 0.93 + 0.80 (log QC-PCR); R2 = 0.81, p < 0.0001] and declined identically following the institution of zidovudine therapy (68-73% decrease from baseline). The close quantitative correlation between bDNA and QC PCR results, and their significant association with other viral markers and CD4+ counts, support the use of plasma viral RNA measurement in HIV-1 clinical trials. PMID- 7786582 TI - Coamplification of HIV type 1 and beta-globin gene DNA sequences in a nonisotopic polymerase chain reaction assay to control for amplification efficiency. AB - The polymerase chain reaction (PCR) fails to detect HIV-1 sequences in 5% of infected individuals. To screen for false-negative PCR tests, we developed a nonisotopic PCR assay in which sequences from the beta-globin gene and from the HIV-1 vpu-env region were coamplified with biotinylated and fluorescein-labeled primers, respectively. Coamplified products were reacted with specific internal digoxigenin-labeled RNA probes. Hybrids were detected in a microtiter plate coated with streptavidin or anti-fluorescein antibody, with enzyme-labeled anti digoxigenin antibody. After the optimization of the coamplification conditions, the assay could detect 5 proviral DNA copies in a lysate from 100,000 peripheral blood mononuclear cells. Fifty-seven samples from 55 HIV-1-seropositive patients and 25 samples from 25 seronegative individuals were evaluated. Fifty-two samples from HIV-infected individuals were positive for HIV-1 vpu-env sequences. Three of the 5 PBMC lysates falsely negative for HIV-1 sequences had reactivities for beta globin (3-23 fu) below that of 100,000 cells (304 fu). Nonisotopic coamplification allowed for the evaluation of the quality of specimens for PCR concurrently with the detection of the presence of viral template sequences. PMID- 7786583 TI - Humoral and cellular immune responses in rhesus macaques infected with human immunodeficiency virus type 2. AB - Eighteen rhesus macaques were inoculated with either an infectious molecularly cloned human immunodeficiency virus type 2 (HIV-2)SBL/ISY, or with one of eight mutants defective in one or more accessory genes. The immune responses generated by the macaques were monitored for up to 2 years postinfection. All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate antibody titers. Macaques inoculated with vpx- mutants exhibited a persistent serological response, suggesting continuous virus expression even in the absence of detectable virus in the peripheral blood mononuclear cells (PBMCs). Neutralizing antibodies developed in only four macaques. In general, low level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs. However, one virus-negative macaque exhibited significant HIV 2-specific CTL activity in an enriched CD8+ cell population from PBMCs, suggesting clearance of the viral infection. In addition, CTL activity against the Env and Gag/Pol epitopes of HIV-2 by CD8+ lymphocytes from the spleens and lymph nodes of two infected macaques, in one case requiring CD8+ T cell enrichment and in the other clearly evident in unfractionated tissue lymphocytes, was demonstrated for the first time. This sequestration of tissue CTLs occurred in the absence of significant levels of circulating CTLs in the blood. Our results suggest that routine monitoring of PBMCs may sometimes be inadequate for detecting cell-mediated immune responses. Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8+ populations. PMID- 7786584 TI - Analysis of envelope glycoprotein-specific antibodies from SIV-infected and gp110 immunized monkeys in ACC and ADCC assays. AB - Sera collected from SIV-infected or recombinant glycoprotein-immunized monkeys were characterized for antibodies participating in antibody-complement-mediated cytolysis (ACC) and antibody-dependent cellular cytolysis (ADCC) in terms of their IgG subclass and epitope specificity. In a competitive inhibition ELISA, gp110-specific antibody reactivity with nondenatured rgp110 was blocked completely by soluble homologous rgp110 and partially inhibited by heterologous rgp110, suggesting cross-reactivity between viral strains. However, only partial inhibition was observed with denatured recombinant gp140 (rgp140) in selected monkeys, indicating that the majority of gp110-specific antibodies recognized conformational epitopes. ACC activity against recombinant vaccinia-infected, envelope-expressing targets was found in sera from both infected and immunized monkeys, whereas ADCC activity was observed only in sera from infected monkeys. ACC was blocked with denatured rgp140 as well as nondenatured rgp110, indicating that ACC-mediating antibodies recognized mainly linear epitopes. In contrast, rgp140 did not compete as effectively as rgp110 in the ADCC assay, indicating that the majority of ADCC antibodies recognized conformational epitopes. Competitive inhibition using three peptide fragments of gp110 indicated that epitopes recognized by ACC antibodies lie within amino acid residues 214-471, a region that spans V3, whereas ADCC-reactive epitopes lie between amino acid residues 52 and 214 at the N-terminal end of gp110. Column chromatography of rhesus IgG resulted in three subclass-enriched fractions, designated IgG-I, IgG II, and IgG-III. IgG-I, but not IgG-II or IgG-III, from both infected and immunized monkeys mediated ACC, whereas IgG-I and IgG-II from infected monkeys mediated ADCC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786586 TI - Evaluation of HIV type 1 western blot-indeterminate blood donors for the presence of human or bovine retroviruses. AB - From 1985 through 1990, 1100 of 500,000 human blood donations in Syracuse, New York were repeatedly reactive by ELISA for antibodies to the human immunodeficiency virus type 1 (HIV-1). Nine hundred of the ELISA-reactive samples were confirmed as negative by Western blot (WB), 40 were confirmed as positive, and the remaining 160 sera were indeterminate, reacting mainly with HIV-1 gag gene products. Twenty donors with the most reactive indeterminate WB were selected for follow-up studies. Four of these 20 donors admitted to retroviral risk factors and, interestingly, 12 (60%) had exposure to dairy cattle and drank unpasteurized milk. These 20 donors were analyzed over a 3-year period for the presence of the pathogenic human retroviruses HIV-1, HIV-2, human T cell lymphoma/leukemia virus types I and II (HTLV-I and HTLV-II), as well as bovine immunodeficiency virus (BIV) and leukemia virus (BLV). Retroviral analyses included serology, plasma antigen capture, virus culture, and the polymerase chain reaction. Only one donor seroconverted and was clearly infected with HIV-1. None of the other 19 donor serological reactivities to HIV-1 changed, nor were they positive for any of the above-mentioned retroviruses. Although we cannot ascertain whether these latter 19 HIV-1 WB-indeterminate donors were exposed to human or bovine retroviral proteins, it is unlikely that their HIV-1 seroreactivity was caused by infection with HIV-1, HIV-2, HTLV-I, HTLV-II, BLV, or BIV. PMID- 7786585 TI - Polyclonal rabbit antisera that detect the Vpr protein of SIVSM and SIVMAC on immunoblots of purified virions. AB - Antisera suitable for detection of SIVSM or SIVMAC Vpr proteins on Western blots of purified virions are currently not available. We have expressed the Vpr protein of SIVSMPBj1.9 in a gst-based prokaryotic expression system and used it to raise polyclonal antisera in rabbits. Two immune sera were obtained that specifically recognized both cell- and virion-associated Vpr protein on immunoblots of three different SIV isolates (SIVSMPBj1.9, SIVMACBK28, and SIVMAC239). Because Vpr is believed to play an important role in HIV/SIV replication and pathogenesis, these reagents will allow the extension of functional analyses of this protein to a broader spectrum of viruses. Both antisera and the gst-Vpr expression plasmid have been submitted to the NIAID AIDS Research and Reagent Program and are available to interested investigators. PMID- 7786587 TI - Differential Tax expression in HTLV type I-infected asymptomatic carriers. AB - tax gene expression in a family cluster of three HTLV-I-infected asymptomatic individuals was investigated. Two carriers had normal tax mRNA, Tax-specific humoral antibody, and cell-mediated immune (CMI) response. In one carrier who had only weak Tax-specific humoral and no Tax-specific CMI response, an abnormal Tax related mRNA product was detected. This product was sequenced and found to consist of two exons derived from the LTR gag and pX regions. The abnormal mRNA has an ORF predicting a 17-kDa protein, the translation of which is initiated in the first exon. The presence of this protein, of antibody to it, and of its function remain to be elucidated. PMID- 7786588 TI - Characterization of the V3 region of HIV-1 isolates from Sydney, Australia. PMID- 7786589 TI - At least five HIV-1 sequence subtypes (A, B, C, D, A/E) occur in England. PMID- 7786590 TI - Non-specialist units, clinical trials and survival from testicular cancer. PMID- 7786591 TI - Should we still advocate referral to specialist centres for teratoma? PMID- 7786592 TI - Long-term prognosis following macroscopic complete response at second-look laparotomy in advanced ovarian cancer patients treated with platinum-based chemotherapy. The Gruppo Oncologico Nord Ovest. AB - Survival (S) and progression-free survival (PFS) were evaluated in 129 advanced ovarian cancer patients, who achieved a macroscopic complete response (112 pathological complete response and 17 microscopic disease) at second-look after platinum-based combination chemotherapy with or without doxorubicin (DX). The impact on S and PFS of age, performance status (PS), stage, histology, grade (G), residual disease after first surgery (RD), chemotherapy regimen, disease status at second-look and consolidation therapy were evaluated by univariate and multivariate analysis. In the 118 months observation period, median S and PFS were 81 and 34 months, respectively. Stage, G, RD, PS and disease status at second-look had significant impact on both S and PFS in univariate analysis, whereas consolidation therapy did not influence outcome. Cox's regression analysis showed that G, RD and PS had an independent impact on PFS. Test for interaction demonstrated no statistically significant relationship between RD, chemotherapy regimen and outcome. In conclusion, advanced ovarian cancer patients with macroscopically complete remission at second-look have a substantial risk of relapse after aggressive treatment. The risk of recurrence was estimated to be maximal in the first 3 years after restaging, and was correlated with poor PS, RD > 2 cm after first surgery and undifferentiated tumour. PMID- 7786593 TI - Is neuro-ectodermal differentiation of Ewing's sarcoma of bone associated with an unfavourable prognosis? AB - Among Ewing's sarcoma (ES) of bone and related entities are tumours with neuro ectodermal features that could represent a biologically distinct type. In order to assess the prognostic significance of the various forms of ES, a retrospective joint study involving three cancer centres in Europe and the U.S.A. was initiated. The material from 315 primary ES was reviewed by a panel of five pathologists and classified as typical ES (220 cases), atypical ES (48 cases) or ES with neuro-ectodermal features (47 cases). Prognostic factor analysis on treatment failure-free survival was performed using the Cox model. It included histopathological classification, initial patient characteristics, clinical presentation and treatment type. After multivariate analysis, in addition to treatment type (P < 0.001), metastases (P = 0.003) and proximal tumour location (P = 0.006), two histopathological parameters correlated with poor treatment failure-free survival, the presence of filigree pattern (P = 0.044) and dark cells (P = 0.043). We conclude that ES with neuro-ectodermal features does not appear to have a different outcome to the other subtypes. PMID- 7786595 TI - Prognostic parameters in localised melanoma: gender versus anatomical location. AB - Extremity location and female gender are both considered favourable prognostic parameters in primary melanoma, but since they cluster in the same group of patients, the question remains as to whether they are both independent variables. Multivariate analysis of 695 patients with primary, localised melanoma was used. The effects of gender and anatomical location were compared directly by sequentially controlling one factor while the other remained free. Following multivariate analysis, significant prognostic factors related to survival were the thickness of the primary lesion (P < 0.0001), the age of the patient at diagnosis (P < 0.0001), the gender of the patient (P = 0.0008) and the anatomical location of the primary lesion (P = 0.005). Thicker lesions, patients older than 50 years, males, and trunk, head and neck locations had poorer prognoses. There was a significant difference in survival according to gender within each location, extremity (P = 0.002) or trunk, head and neck (P = 0.0004); however, there was no significant difference in survival according to anatomical location within each gender, male (P = 0.11) or female (P = 0.29). The thickness of the primary lesion, the age of the patient at diagnosis, the gender and the anatomical location of the melanoma are all significant prognostic parameters in localised melanoma. Gender appears to have a more pronounced effect on survival than anatomical location. PMID- 7786594 TI - Different dose regimens of 5-fluorouracil and interferon-alpha in patients with metastatic colorectal carcinoma. AB - Three different 5-fluorouracil (5-FU)-interferon-alpha-2b (IFN)-containing regimens were designed for treatment of patients with advanced colorectal cancer. 87 patients with a Karnofsky index > or = 70 were included in three sequential non-randomised phase II trials. Regimen A consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by weekly 1-h intravenous infusions until week 8. IFN (5 MU) was given subcutaneously on days 1, 3 and 5 followed by injections (9 MU) every second day until week 8. The cycle was then repeated. Regimen B consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by 5-min intravenous injections on days 12 and 19. IFN (3 MU) was given subcutaneously on days 1-5 followed by injections (5 MU) on days 11-13 and 18-20. The cycle was repeated every fourth week. Regimen C consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5. IFN (3 MU) was given subcutaneously on days 1-5. The cycle was repeated every third week. The objective response rates (complete response (CR) and partial response (PR)) after approximately 4 months of therapy or longer were as follows: regimen A (n = 27) 22% (2 CR, 4 PR), regimen B (n = 33) 42% (4 CR, 10 PR) and regimen C (n = 27) 22% (1 CR, 5 PR). The corresponding response figures for previously untreated patients were regimen A 50%, regimen B 64% and regimen C 38%. Response durations varied from a few weeks up to 142 + weeks. Toxicities were generally mild and reversible, and the treatments were convenient for the patients and cost effective since the 5-day infusions could be given by a portable pump without hospitalisation. Our results are in agreement with those of others showing that 5 FU/IFN combinations can be highly effective in advanced colorectal cancer, and that a number of factors such as doses, dose intensities, infusion rates and timing of the two drugs may be crucial for the anti-tumour activity of this drug combination. PMID- 7786596 TI - Timing of surgery during the menstrual cycle for breast cancer: possible role of growth factors. AB - Premenopausal patients undergoing surgery for breast cancer were prospectively studied. Data regarding menstrual history, pathological parameters and hormone receptor status were collected. Serum oestradiol, prolactin and progesterone levels, tumour epidermal growth factor receptor (EGFR) levels, tumour epidermal growth factor (EGF) levels and flow cytometry were measured. Patients were allocated to the follicular or luteal phase of their cycle both by history and progesterone level. No significant differences were seen in hormone receptor levels, pathological parameters or EGF levels between the two groups. EGFR levels were significantly higher in women undergoing surgery during the follicular phase of their cycle, when classified by menstrual history. Patients operated on during this phase have previously been found to have a poorer prognosis, and these results may provide a basis for this finding. This may have implications for prognosis and timing of surgery, and further investigation is warranted. PMID- 7786597 TI - Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival. AB - The expression of retinoblastoma gene product (Rb protein) was studied by immunohistochemical analysis of 205 cases of breast cancer. Rb protein was invariably expressed in non-neoblastic breast epithelium, in dysplastic and hyperblastic lesions adjacent to tumours, and none of the breast tumours was totally negative for Rb protein. According to the scoring system used, the expression of Rb protein was abnormal in 36.6% of cases. Abnormal expression of Rb protein was significantly related to grade (P < 0.00004), type (P = 0.0183), margin formation (P = 0.0116), DNA ploidy (P < 0.0002) and nuclear pleomorphism (P < 0.0001). Abnormal expression of Rb protein was related to high S phase fraction (P = 0.004), high mitotic index (P < 0.001) and high morphometric nuclear factor values (P < 0.01). The expression of Rb protein had no prognostic value in univariate or multivariate analysis. The results show that the tumour suppressor gene Rb participates in the growth regulation of breast cancer cells in vivo, but immunohistochemical assessment of the expression of Rb protein has no prognostic significance in clinical breast cancer over already established prognostic factors. PMID- 7786598 TI - Parathyroid hormone-related protein (PTHrP) in breast cancer and benign breast tissue. AB - Parathyroid hormone-related protein (PTHrP) 1-86 was quantified by immunoassay in extracts of 132 breast cancers, 27 samples of normal breast tissue and four fibroadenomas. PTHrP 1-86, was detected in 68% of primary tumours (range 40 302,000 fmol/g), 33% of normal breast tissues (range 100-1800 fmol/g), and all four fibroadenomas (range 110-11,600 fmol/g). PTHrP displayed molecular heterogeneity on gel filtration chromatography, and 1-86, 1-34 and 37-67 immunoreactivity eluted as 25-27 kDa together with a peak of 19-21 kDA containing only 37-67 activity. Tumour PTHrP 1-86 levels correlated inversely with age (P < 0.05) and were higher in premenopausal women (P = 0.05). The proportion of tumours containing PTHrP was higher in axillary node positive premenopausal women (P < 0.05). These data suggest that oestrogen may regulate expression of PTHrP in breast cancer and that production of PTHrP may be linked to development of axillary node metastases. PMID- 7786600 TI - A model-based prediction of the impact on reduction in mortality by a breast cancer screening programme in the city of Florence, Italy. AB - The efficacy of breast cancer screening for women older than 50 years has been shown in several studies. Service screening is now ongoing or planned in several countries in Europe. MISCAN, a computer simulation programme, has been used to analyse data from the Florence District Programme (FDP) breast cancer experience. First, the model was fitted to the screening results for the period 1975-1986. A good correspondence between the model outcomes and the FDP results was achieved. It was then used to predict the impact on mortality of the new starting programme of the city of Florence (63,000 women, 50-69 years old). Assuming a 70% attendance rate, then for the city of Florence, 2563 screen-detected breast cancers are predicted for the period 1991-2020 out of the total number of 9095 breast cancers for all ages (28%). A total of 3720 deaths for breast cancer are expected without screening. An absolute reduction of 472 deaths (13%) is predicted for the whole population. The estimated number of years of life gained by screening until 2020 is 4354. Simulation by MISCAN has previously been a useful support tool for decision-making about screening. The present paper is the first based on a southern European experience. The possibility of applying MISCAN to predict the impact of a national programme in Italy is discussed. PMID- 7786601 TI - Trends in cervical cancer incidence in the district of Florence. AB - The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30 39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50 59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population. PMID- 7786599 TI - Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: results of a phase I-II study by the GOTHA group. Group d'Oncologie Thoracique des Regions Alpines. AB - The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. PMID- 7786602 TI - Cycloplatam: a novel platinum compound exhibiting a different spectrum of anti tumour activity to cisplatin. AB - Cycloplatam is a novel platinum compound which has shown anti-tumour activity in murine tumour models. In this study, cycloplatam was found to have anti-tumour activity in vitro and in vivo in human tumour models. In 15 cell lines (mainly ovarian), cycloplatam showed similar cytotoxicity as cisplatin, using the sulphorhodamine B assay. Determination of the resistance factor (IC50 of cisplatin-resistant divided by IC50 of parental cell line) clearly showed lower values for cycloplatam than for cisplatin. In the parental ovarian cell line CH1 and the cisplatin-resistant CH1 cisR model, we observed no cross-resistance of cycloplatam and cisplatin. The in vitro anti-tumour activity was confirmed in human tumour xenografts using the clonogenic assay. Mean IC70 values of cycloplatam were 0.54 microgram/ml (1.25 microM) and of cisplatin 0.42 microgram/ml (1.4 microM), respectively. In the murine subcutaneously implanted ADJ/PC6 plasmacytoma in vivo cycloplatam showed less activity than cisplatin, with a 2-fold smaller therapeutic index than cisplatin. In ovarian cancer xenografts cycloplatam was less active than cisplatin. However, anti-tumour activity of cycloplatam in lung cancer xenografts was quite different from cisplatin. In LXFS 538, a model moderately sensitive to cisplatin, a partial remission was observed, but in LXFL 529, a cisplatin-sensitive model, cycloplatam was inactive, cycloplatam thus demonstrating a different spectrum of anti-tumour activity. Based on these results, further preclinical investigations with other tumours, such as cisplatin-sensitive and -resistant gastric cancer models, are warranted with cycloplatam. PMID- 7786603 TI - Growth factor requirement, oncogene expression and TP53 mutations of a tumorigenic and a non-tumorigenic subline of the human breast carcinoma cell line, HMT-3909. AB - From a human breast carcinoma cell line, HMT-3909, a tumorigenic and a non tumorigenic subline have previously been described. Cells of both sublines have been characterised as carcinoma cells. In the present work we examined whether differences in growth factor requirements or oncogene expression may explain the difference in tumorigenicity. We found that exogenous growth factor dependence discriminated between the two sublines. No alterations in oncogenes or tumour suppressor genes were demonstrated that could explain the differences in tumorigenicity. The lower growth factor requirement and the higher growth rate of the tumorigenic subline indicates that, in these cells, growth potential may determine the outcome of the tumorigenicity assay. PMID- 7786604 TI - Prophylaxis and therapy of mouse mammary carcinomas with doxorubicin and vincristine encapsulated in sterically stabilised liposomes. AB - This study tested the prophylactic efficacies of doxorubicin hydrochloride and vincristine sulphate, encapsulated in sterically stabilised long circulating liposomes, against the spontaneous development of mammary carcinomas in C3H/He mice. Monthly prophylactic intravenous (i.v.) injections of 6 mg/kg doses of liposome-encapsulated doxorubicin (DOX-SL) or 1 mg/kg doses of liposome encapsulated vincristine (VIN-SL) were begun when retired breeding mice were 26 weeks old. Mice that developed a mammary carcinoma while on the monthly prophylactic protocols were then given weekly i.v. injections of 6 mg/kg DOX-SL or 1 mg/kg VIN-SL to test the therapeutic efficacies of the drugs, and to determine whether the tumours were susceptible or resistant to therapy. The monthly prophylactic injections reduced the incidence of first mammary carcinomas from 87/88 (99%) in untreated mice to 24/42 (57%) in DOX-SL-treated mice and to 26/32 (81%) in VIN-SL-treated mice. Of the mice that developed a mammary tumour while on the prophylactic protocols, 12 of 30 mice were cured by the weekly therapeutic use of DOX-SL, and the growth of 18 tumours was inhibited. The weekly therapeutic use of VIN-SL cured 3 of 8 mice, and inhibited the growth of five tumours. Weekly DOX-SL therapy cured 7 of 22 previously untreated mice. The mean survival of tumour-bearing mice was extended from 24 days in untreated mice to 87 days in DOX-SL-treated mice, which had not received prophylactic treatment. Metastases were found in 29 of 54 untreated mice, and in 3 of 72 mice treated with DOX-SL and VIN-SL. Toxic side effects were limited to a transient weight loss during the weekly treatments. Drug resistance as a result of treatments was not observed. PMID- 7786605 TI - Opposite effect of miltefosine on the antineoplastic activity and haematological toxicity of cyclophosphamide. AB - The effect of pretreatment with miltefosine (MIL) on the antineoplastic activity of cyclophosphamide (CPA) was evaluated in subcutaneous benzo(a)pyrene-induced sarcomas (BPS) of the rat. MIL alone had no antineoplastic effect on this autochthonous tumour, but enhanced the chemotherapeutic effect of CPA. Conversely, MIL counteracted the myelotoxicity of CPA in normal adult rats. Although the nadir of the leucocyte count remained unchanged, the recovery phase was considerably shortened, an effect which resembled the pharmacological action of GM-CSF. PMID- 7786606 TI - KT-5720 reverses multidrug resistance in variant S49 mouse lymphoma cells transduced with the human MDR1 cDNA and in human multidrug-resistant carcinoma cells. AB - T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy. PMID- 7786607 TI - Failure of liposomal encapsulation of doxorubicin to circumvent multidrug resistance in an in vitro model of rat glioblastoma cells. AB - We studied the capacity of doxorubicin encapsulation in liposomes of various lipid compositions to circumvent multidrug resistance in several variants of the C6 rat glioblastoma cell line in culture, and to inhibit azidopine binding to membranes isolated from these cells. Three formulations of liposomes were prepared: (a) phosphatidylcholine (PC)/phosphatidylserine (PS)/cholesterol (cho) at a 9/24 ratio; (b) PC/cardiolipin (CL)/cho at 10/1/4 ratio; (c) dipalmitoylphosphatidylcholine (DPPC)/cho at 11/4 ratio. Unloaded liposomes presented no cytotoxicity against sensitive or resistant cells. Doxorubicin encapsulated in PC/PS/cho and PC/CL/cho liposomes had a cytotoxic activity close to that of free doxorubicin, whereas doxorubicin encapsulated in DPPC/cho liposomes was significantly less active than free doxorubicin in sensitive as well as in two of the three multidrug resistant cell lines, and as active as free doxorubicin in the third one. Free doxorubicin was able to decrease 50% of [3H]azidopine photolabelling to P-glycoprotein at a concentration of 40 microM; doxorubicin encapsulated in PC/CL/cho or PC/PS/cho liposomes was able to inhibit [3H]azidopine binding similarly as free drug, whereas doxorubicin encapsulated in DPPC/cho liposomes had no significant effect on this parameter. Unloaded liposomes of either lipid composition had no effect on [3H]azidopine binding. Together with physical studies performed in parallel on doxorubicin trapping in liposomes (J Liposome Res 1993, 3, 753-766), these results suggest that doxorubicin leaked out of fluid liposomes (PC/PS/cho or PC/CL/cho), whereas rigid liposomes (DPPC/cho) were able to sequester the drug more efficiently. In that case, however, no availability of the drug to the cells was possible and only a weak cytotoxicity was exhibited, especially without any favourable effect on multidrug resistance. In conclusion, no reversal of doxorubicin resistance was found to occur through liposomal encapsulation of the drug. PMID- 7786608 TI - Clonal diversity, measured by heterogeneity of Ig and TCR gene rearrangements, in some acute leukaemias of childhood is associated with a more aggressive disease. AB - The pattern of immune system gene rearrangements in acute leukaemias of childhood is heterogeneous. The biological significance of this heterogeneity in childhood acute leukaemia is still poorly understood. In this study, we analysed 49 children with acute leukaemia (29 B-precursor acute lymphoblastic leukaemia (ALL), 5 relapsed cALL, 6 T-ALL, 7 acute non-lymphocytic (ANLL) and 2 mixed lineage leukaemias), for the presence of different immune system gene rearrangements (Ig JH, C kappa, C lambda, TCR J gamma, C beta, J delta and J alpha) by Southern blot hybridisation. The most prominent heterogeneity of immune system gene rearrangements was observed in the group of B-precursor ALL. The results from our study suggest that the heterogeneity of immune system gene rearrangement reflects clonal diversity in approximately one-third of patients with B-precursor ALL at presentation and in most patients in relapse. The observed association of clonal diversity with high white blood cell count, pre-B immunophenotype and age under 1 year in B-precursor ALL may have clinical significance. There was a significantly shorter disease-free survival in the group of B-precursor ALL patients with clonal diversity compared with those without clonal diversity. Clonal diversity may, therefore, be a mechanism of disease progression common to different types of aggressive B-precursor ALL. PMID- 7786609 TI - Revisions of general guidelines for the preclinical toxicology of new cytotoxic anticancer agents in Europe. The Cancer Research Campaign (CRC) Phase I/II Clinical Trials Committee and the European Organization for Research and Treatment of Cancer (EORTC) New Drug Development Office. PMID- 7786610 TI - Steroid receptor distribution in 47,892 breast cancers. A collaborative study of 7 European laboratories. The EORTC Receptor Study Group. AB - Seven laboratories of the EORTC Receptor Study Group reported the distribution of oestrogen (ER) and progesterone receptors (PR) routinely assayed in breast cancer cytosols. A low interlaboratory variability was demonstrated for the median values, and for the frequency of positive tumours as measured by enzyme immunoassay (EIA). Larger variations were found for the frequency of positive tumours, as measured by radioligand binding assay (RLA). They are probably due to differences in the cut-off levels and in the sensitivity of the assay. Analysis of the variability over time clearly demonstrated that the ER-EIA values initially increased compared with RLA. A possible source of variations could be the calibration drift in the ER-EIA kit. In conclusion, quality assessment of steroid receptors should be monitored by comparison of both common standards and distributions routinely obtained in each laboratory. In-house analysis over time is also essential for reagent survey. PMID- 7786611 TI - Resection of a solitary brain metastasis in a patient with small cell lung cancer -long-term survival. PMID- 7786612 TI - The metabolite N-4-methoxyphenylretinamide is a major determinant of fenretinide induced decline of plasma insulin-like growth factor-1. PMID- 7786614 TI - Hepatic angiosarcoma in a patient with essential thrombocythaemia and Budd-Chiari syndrome. PMID- 7786613 TI - Fotemustine and tamoxifen combination therapy in metastatic malignant melanoma. A phase II study. PMID- 7786615 TI - Evidence of responsiveness to chemotherapy in aggressive Rosai-Dorfman disease. PMID- 7786616 TI - Effective stimulation of thrombopoiesis with interleukin-3 in chemotherapy induced myelosuppression--a case report. PMID- 7786617 TI - Prospective analysis of the information level of Italian cancer patients. PMID- 7786618 TI - [Hippocampus and memory disturbance: study on cases of transient global amnesia with dysfunction in the medial temporal lobe]. PMID- 7786619 TI - [Amnesia due to thalamic lesion]. PMID- 7786620 TI - [Basal forebrain lesions and memory disorders]. PMID- 7786621 TI - [Amnesia due to fornix and retrosplenial lesion]. PMID- 7786622 TI - [Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion]. AB - Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300. PMID- 7786623 TI - [Subset analysis of tumor infiltrating lymphocytes and peripheral blood lymphocytes in malignant glioma patients]. AB - It has already been reported that T cell infiltration is observed in brain tumor tissue but that general cellular immunity is suppressed in malignant brain tumor patients. In this report, the subsets of tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) were analyzed in 8 patients with malignant glioma in order to investigate the relationship between the local and systemic immunological response in malignant brain tumor patients. TIL subsets in surgical specimens were analyzed immunohistochemically using the ABC method and monoclonal antibodies of the Leu series (anti-Leu 2a, 3a + b, 4 + 5b, 7, 12 and M5), and identified more precisely by double immunofluorescence staining (DIFS) using paired fluorescein isothiocyanate (FITC)-Leu 3a + b and phycoerythrin (PE) Leu8 or FITC-Leu 2a and PE-Leu 15. PBL subsets were determined preoperatively by two-color analysis with a fluorescence-activated cell sorter (FACS) using fluorescence-labeled monoclonal antibodies (paired FITC-Leu 4 and PE-Leu 12, FITC Leu 3a and PE-Leu 8, or FITC-Leu 2a and PE-Leu 15). Most TILs proved to be T lymphocytes containing Leu 3a + b+ (T helper/inducer) cells and Leu 2a+ (T suppressor/cytotoxic) cells in almost equal numbers, but there were too few TILs to kill the tumor cells. Detailed examination by DIFS revealed that 93% of the Leu 3a + b+ cells were helper T cells (Leu3a + b+.Leu8- cells) and that 88% of the Leu 2a+ cells were cytotoxic T cells (Leu 2a+.Leu15- cells). Analysis of PBLs showed statistically significant decreases in T cells as a whole and in helper T cells (Leu 3a+.Leu 8- cells).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786624 TI - [Jacksonian seizure model induced by a kainic acid microinjection into unilateral sensori-motor cortex]. AB - Kainic acid microinjection into unilateral sensori-motor cortex induced focal seizure status and secondarily generalized seizure status for about 4 hours. After these seizure status, focal myoclonic jerkings were induced for about 2 days. EEG demonstrated generalized synchronous periodic spikes with these myoclonic jerkings. This phenomenon was very similar to those symptoms of epilepsia partialis continua in man. During focal seizure status, autoradiographic study with 14C-deoxyglucose demonstrated increased local cerebral glucose utilizations in the injected site of the sensori-motor cortex, ipsilateral caudate nucleus, globus pallidus, substantia nigra and thalamic nuclei. The result suggested that subcortical pathways played an important roles in the seizure propagation from the cortical epileptogenic focus. PMID- 7786626 TI - [Prognostic evaluation of patients with severe head injury by motor evoked potentials induced by transcranial magnetic stimulation--combined analysis with brainstem auditory evoked potentials]. AB - Prognostic evaluation of severe head injury was performed on the basis of transcranial magnetic motor evoked potentials (MEPs) and brainstem auditory evoked potentials (BAEPs). The subjects were 43 severe head injury patients with Glasgow Coma Scale Scores (GCS) of 9 or less. MEPs were recorded within 3 days after the injury. Patient outcome at 1, 6 and 12 months after the injury was correlated with the MEPs and BAEPs. Differences between MEP and BAEP findings in focal lesions and diffuse lesions also were analyzed. MEP wave latencies and inter-peak latencies between BAEP waves IV and V and between waves I and V were evaluated. There was a closer relationship between MEP latency and GOS, especially between the good recovery group and other outcome groups. At 1 month after the injury, there was a closer correlation between MEP latency and BAEP latency in those who died than in those who survived, and this tendency was more evident with regard to focal lesions. However, there was no significant correlation between MEP and patient outcome when the lesions were diffuse. There was no correlation between BAEP latencies and patient outcome, but there was a good, close correlation between prolonged MEP latency and unfavorable outcome at 1, 6, 12 months after injury. In conclusion, the combined use of BAEPs and MEPs induced by transcranial magnetic stimulation is useful in prognostic evaluation of acute head injury patients, especially when the brain lesions are focal. PMID- 7786625 TI - [The effects of mild hypothermia on expression of stress protein (HSP72) after experimental brain injury]. AB - Recent studies have demonstrated that mild hypothermia protects brain from ischemic insults. In the present study, we investigated the effects of mild hypothermia on stress responses of the neurons and glia after experimental brain injury. We evaluated the immunocytochemical expression of 72kDa molecular weight heat shock protein (HSP72) as a marker of cellular injury. Adult male Sprague Dawley rats were subjected to a lateral fluid percussive injury. After injury the animals were divided into two groups (normothermic and hypothermic groups). Body temperature of the normothermic groups was maintained at 37.0-37.5 degrees C throughout the experiment. In the latter groups, the rats were exposed to hypothermia of 30.0-31.5 degrees C by surface cooling for 150 minutes beginning at 15 minutes after injury. Animals in each groups were sacrificed at 24, 48, and 72 hours after injury. Vibratomed brain sections were provided for immunocytochemical staining of HSP72 and hematoxyline-eosin staining. The induction of HSP72 was evaluated under the light microscopic level. Results 1) The rats that produced HSP72 in the hypothermic group were significantly less than those in the normothermic group. 2) HSP72 was expressed in the neurons and glia in the various brain regions including the impact site, parasagittal cortex, deep cortical layer, hippocampus, caudate-putamen and midbrain in both groups. However HSP72 positive cells in each brain region of the hypothermic group were significantly less than those in the corresponding regions of the normothermic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786627 TI - [HTLV-I-associated neuropathy]. AB - A 70-year-old man was admitted to our hospital because of a 15-year history of walking difficulty, disturbance of sensation in the palm for 2 years and hand tremor for 6 months. On admission, the scapulohumeral muscles showed fasciculation and atrophy. There was action tremor in the upper limb, and the proximal lower limb showed atrophy and weakness. Standing and walking were impossible. Deep tendon reflexes were decreased in lower limbs. Pathologic reflexes were not found. There was distal dominant sensory disturbance, and urination was difficult. Needle EMG showed a neurogenic pattern in 4 all limbs. MCV and F-latency were delayed. SCV in the median nerve and the amplitude in the sural nerve were decreased. Biopsy of the sural nerve revealed both axonal change and demyelination. Biopsy of the quadriceps femoris muscle showed neurogenic change with helper T-cell infiltration. Anti-HTLV-I antibody and ATL-like cells in both blood and CSF were positive. There were HTLV-I provirus DNA with a polyclonal pattern and the type of HLA as HAM. The HTLV-I infection was of the HAM type. As the present patient showed mainly neuropathy without pyramidal signs, was not considered to have HAM. PMID- 7786628 TI - [A case of deep sylvian meningioma presenting temporal lobe epilepsy]. AB - A rare case of deep sylvian meningioma is presented. A 62-year-old woman was admitted to our hospital because of one year history of temporal lobe epilepsy. She had no neurological deficit except for EEG abnormality. CT scans showed a small calcified mass in the left temporal lobe adjacent to the sylvian fissure with no enhancement by contrast medium. The mass was low-intense in both T1- and T2-weighted MR images. The T1-weighted image after the infusion of gadolinium revealed enhancement of the middle cerebral artery adjacent to the mass, similar to dural tail sign. Left external carotid angiography did not show any tumor stain nor the dilatation of the middle meningeal artery. Left internal carotid angiography disclosed enlarged middle cerebral artery without tumor stain. A left frontotemporal craniotomy was performed and the mass was totally removed. The tumor was located deep in sylvian fissure without any connection to the dura or ventricular system, which was firmly adherent to the middle cerebral artery. The histological examination of the surgical specimen revealed a psammomatous meningioma. Meningiomas are believed to originate from the arachnoid cap cells and can arise from various intracranial locations where arachnoid cap cells exist. The majority of them are attached to the dura, choroid plexus, or the tela choroidea. Only eleven cases of deep sylvian meningiomas have been presented in the literature. We have reviewed the clinical and radiological findings in such meningiomas. MR findings in deep sylvian meningioma have not been described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786629 TI - [A 21-year-old man with distal dominant progressive muscle atrophy]. AB - We report a 21-year-old man with distal dominant progressive muscle atrophy. The patient was apparently well until 17 years of age when he noted a decrease in exercise tolerance. One year later, he noted difficulty in arising his heels when the walked. He was admitted to our service for the work up in June 10, 1992. On admission, the patient was rather slender in the body build up; otherwise general physical examination was unremarkable. Upon neurologic examination, mental status and higher cerebral functions were normal. In the cranial nerves, the sternocleidomastoid muscles were atrophic bilaterally; other cranial nerves appeared intact. His gait was unstable and he showed steppage gait; walking on toes and heels were impossible. Distal dominant muscle atrophy was noted in both upper and lower extremities. Muscle strength in the deltoid, biceps brachii and triceps brachii was normal. In the lower extremities, both tibialis anterior and triceps surae muscles were weak (3/5). The iliopsoas and quadriceps femoris muscles were normal, however, the adductor muscles of the thigh showed marked weakness (2/5). Myotonia was absent. Deep reflexes were decreased; sensation was intact. Routine blood tests were unremarkable; CK was 96 IU/l, lactate 6.9 mg/dl, and pyruvate 0.61 mg/dl. After an ischemic forearm exercise test, blood lactate level rose to 22.5mg/dl (base line 11.2), and blood ammonia to 88.3 micrograms/dl (base line 71.2). EMG showed myogenic changes and myotonic discharges. A diagnostic biopsy was performed. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had type III glycogen storage disease. The differential diagnosis included rimmed vacuole type myopathy, Miyoshi type distal muscular dystrophy, Welander type muscular dystrophy, adult type acid-maltase deficiency, and lysosomal glycogen storage disease with normal acid maltase. However, characteristic clinical presentation of initial weakness in the triceps surae muscle associated with atrophy of the sternocleidomastoid muscle confirmed best of the clinical characteristics of type III glycogen storage disease; the only finding which did not fit with its diagnosis was elevation of the blood lactate level after the ischemic exercise test. The muscle biopsy specimen showed marked vacuole formation; approximately 20 to 30% of the vacuoles were rimmed vacuoles, however, the majority was not rimmed. PAS staining on an epon-embedded specimen revealed marked accumulation of PAS-positive materials in those vacuoles as well as in the interfascular space. The non-rimmed vacuoles were not positively stained in the acid-phosphatase staining, which exclude the diagnosis of acid maltase deficiency. No mitochondrial abnormalities were found.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7786630 TI - What role does the osteocyte network play in bone adaptation? PMID- 7786631 TI - Osteoblasts and osteoclasts in adult human osteophyte tissue express the mRNAs for insulin-like growth factors I and II and the type 1 IGF receptor. AB - Insulin-like growth factors (IGFs) are among the most abundant growth factors present in bone. In vitro, bone-derived cells both produce and respond to IGFs I and II, suggesting that these growth factors play an autocrine role in the regulation of bone turnover. In vivo, however, particularly in adult bone, their sites of expression have not been well documented. We have used, therefore, the technique of in situ hybridization to study the expression of the mRNAs for IGFs I and II and the type 1 IGF receptor in adult human osteophyte tissue. Throughout the developing osteophyte there was a strong association between osteogenesis and the expression of all three mRNA transcripts. The highest levels of expression were observed in active osteoblasts. Hybridization signals were weak or absent in flat cells lining quiescent surfaces and in cells of the bone marrow, including those that expressed alkaline phosphatase activity. Osteocytes and cells of the periosteum were negative. At sites of endochondral bone formation newly differentiated and hypertrophic chondrocytes expressed the mRNAs for IGFs and IGF receptor whereas cells of the perichondrium were negative. A striking finding of this investigation was that osteoclasts at sites of bone and calcified cartilage resorption expressed high levels of all three mRNA transcripts. These results support the hypothesis that locally produced IGFs are important regulators of bone formation. The differential expression of all three transcripts among cells of the osteoblast lineage suggests that IGFs may be involved in the maintenance of the mature osteoblast phenotype rather than in inducing the differentiation of marrow precursors or controlling the osteoblast-osteocyte transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786632 TI - Do ultrasound measurements on the os calcis reflect more the bone microarchitecture than the bone mass?: a two-dimensional histomorphometric study. AB - Few studies have analyzed the relationship between ultrasound measurements (US) and corresponding histomorphometric parameters of the calcaneus. To address this question we have compared US and histomorphometric parameters in 17 whole human os calcis from amputation or necropsy. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and bone mineral density (BMD) were measured on the whole foot at the calcaneal site using an Achilles device and a DPX-L densitometer (Lunar). The os calcis was dissected and a 1-cm-wide transcortical parallelepiped extracted with a biopsy needle, focused on the center of the measured area. Histomorphometry was performed on undecalcified biopsies. Structural and connectivity parameters were measured on 7-microns-thick sections with both automatic (Biocom) and semiautomatic analyzers (Ibas 1, Kontron). We found that all ultrasonic and densitometric parameters reflected the true amount of bone and were correlated with only some of the parameters reflecting bone microarchitecture. From stepwise regression analysis, we found that 68%, 67%, 72%, and 74% of the variance of SOS, BUA stiffness, and BMD, respectively, were explained significantly by trabeculae thickness only. Ultrasonic measurements appear to reflect bone quantity rather than bone microarchitecture. The current conclusion is fairly negative with respect to the ability of ultrasound to assess structural parameters, but our limited sample size did not give enough power to our study to reach statistically significant correlations. In addition, the calcaneus is anisotropic and the ultrasound interaction in bone is a three dimensional phenomenon. So, a three-dimensional study rather than a two dimensional one should be performed. PMID- 7786633 TI - Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age. AB - The vertebral bodies of the complete spine (C-3-L-5) were removed in 26 autopsy cases without evidence for primary or secondary bone disease (13 males aged 19-79 years and 13 females aged 17-90 years). A sagittal segment through the center of all vertebral bodies was embedded undecalcified in hydroxyethylmethacrylate and processed to so-called surface stained block grindings. Histomorphometric analysis of the complete segment was performed using a computer-assisted image analysis system (IBAS 2000). The structural parameters investigated were bone volume (BV/TV) and trabecular interconnection quantificated by trabecular bone pattern factor (TBPf). A close correlation of BV/TV and TBPf was found in all vertebral bodies irrespective of vertebral region (r = 0.8, p < 0.001). This indicates that the age-related decrease of trabecular bone mass is primarily the consequence of the transformation from plates to rods and the loss of whole trabecular structures. This basic principle is valid throughout the complete spine. However, the systematic analysis of vertebral trabecular bone from C-3 to L-5 revealed a significant intervertebral variation of trabecular microarchitecture. The density of trabecular structure of cervical vertebrae is much higher than that of thoracic and lumbar vertebrae (p < 0.001). The extent of age-related loss of trabecular bone mass and structure showed a decrease within the spine from the caudal to the cranial region (p < 0.05). The loss of bone volume in individuals between the ages of 30 and 80 years in the lumbar spine was 53%, whereas in the thoracic spine the decrease was 41%, and in the cervical spine only 24%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786634 TI - Stimulation of bone formation by dynamic mechanical loading of rat caudal vertebrae is not suppressed by 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP). AB - We have recently developed an experimental system whereby pins inserted into the seventh and ninth caudal vertebrae of rat tails are used to load the eighth caudal vertebrae (C-8) in compression. In this model, a single 5-min period of dynamic loading, sufficient to induce strains within the range to which bones are exposed under physiological circumstances, stimulates lamellar bone formation in the cancellous bone of the vertebrae. The rapidity with which the increase in bone formation was induced raised the possibility that this bone formation might have occurred without prior resorption. To test the role of bone resorption in the response of the bone to mechanical stimulation, we compared the anabolic response to a single period of loading, of rats treated with 3-amino-1 hydroxypropylidene-1-bisphosphonate (AHPrBP) or vehicle. We found that mechanical loading caused a significant increase in dynamic and static indices of bone formation. The same indices were unaffected by AHPrBP, while the bone formation rate in the tibiae was reduced by AHPrBP. These results suggest that the increased bone formation induced by mechanical stimulation in the cancellous bone of rat vertebrae is not dependent on bone resorption. PMID- 7786635 TI - Predicting vertebral deformity using bone densitometry at various skeletal sites and calcaneus ultrasound. AB - We investigated the usefulness of bone density measurements from multiple skeletal sites and calcaneus ultrasound for evaluating the probability of vertebral deformation. Bone mineral density (BMD) was measured at the second metacarpal and middle phalanges using radiographic absorptiometry of hand radiographs, and at the lumbar spine using dual-energy x-ray absorptiometry. Distal radius and proximal radius were measured using single-energy x-ray absorptiometry (SXA), expressed as bone mineral content (BMC, grams per centimeter), and as BMD (grams per square centimeter). The calcaneus was measured using both SXA (BMD) and broadband ultrasound attenuation (BUA). Among the women in this study (mean age 74, SD = 5), 84 women developed new vertebral deformations (57 cases with one and 27 cases with two or more deformations), which were identified on serial radiographs during an average of 9 years prior to the measurements of bone density. Logistic regression analysis was used to calculate odds ratios for risk of deformation corresponding to a 1-SD difference in density or ultrasound, adjusted for age. All bone measurements were significantly associated with vertebral deformation, with odds ratios (95% confidence intervals) ranging from 1.40 (1.10, 1.78) for proximal radius BMD to 1.88 (1.45, 2.44) for calcaneus BMD measurements. Measurements of calcaneal BUA, calcaneal BMD, and hand BMD generally remained significant when included simultaneously with another measurement in the same model, suggesting that spine or radius BMD may not provide much additional information about risk of deformation. It appears that all of the measurements of bone density and ultrasound provide useful information regarding the probability of deformation. These findings await confirmation in a prospective study. PMID- 7786637 TI - Evidence for the synthesis of parathyroid hormone-related protein (PTHrP) by nontransformed clonal rat osteoblastic cells in vitro. AB - Parathyroid hormone-related protein (PTHrP) is synthesized by a variety of tumors and is thought to be the main cause of the clinical syndrome of humoral hypercalcemia of malignancy (HHM). In addition to its parathyroid hormone (PTH) like actions, novel actions of PTHrP on placental calcium transport and inhibition of in vitro osteoclast activity have been demonstrated. The fact that osteoblasts act as mediators of osteoclastic bone resorption prompted us to investigate whether nontranformed, osteoblastlike cells produce PTHrP. PTHrP has been detected in developing human fetal bones and in rat long bones in culture. For this study, osteogenic cells, CRP 5/4 and CRP 10/30, were employed. Both cell types represent clonal bone cell populations established from 1-day-old rats. While CRP 10/30 cells express the osteoblastic phenotype, CRP 5/4 cells resemble cells with preosteoblastic properties. With a radioimmunoassay (RIA), utilizing antiserum directed against the amino-terminal PTHrP(1-40), it was found that both cell types synthesize PTHrP constitutively. CRP 10/30 cells produce about twice as much as CRP 5/4 cells. Transforming growth factor-beta (TGF-beta 1) was shown to increase the synthesis of PTHrP in CRP 5/4 cells by about 2.5-fold, while in CRP 10/30 cells it caused an approximate 50% reduction of PTHrP. Employing the reverse transcriptase polymerase chain reaction (RT-PCR) technique it was found that both bone cell types express mRNA for PTHrP and that the modulation of the PTHrP mRNA levels by TGF-beta 1 in CRP 5/4, and to a lesser degree in CRP 10/30 cells, was reflected in a change in the level of PTHrP protein in the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786636 TI - Hypercalciuria in osteogenesis imperfecta: a follow-up study to assess renal effects. AB - In 1991, we reported that hypercalciuria is a common finding in our pediatric patient population with osteogenesis imperfecta (OI) (17 of 47 = 36%). Here, we prospectively screened 12 of these hypercalciuric children, on average 4 years subsequent to the discovery of elevated urine calcium levels, for adverse effects on renal function. Despite an ad libitum decrease since initial investigation of about 30% in their previously normal dietary calcium intake (adjusted for body weight), 8 of the 12 patients remained hypercalciuric (urine calcium/creatinine > 0.62 mmol/mmol). We found, once again, that urinary calcium levels significantly correlated with the severity of the skeletal disease as assessed by z-score for height (r = -0.75, p = 0.005). Evaluation of kidney function, however, revealed: (i) normal routine urinalysis in all but 1 subject who had transient microscopic hematuria; (ii) unremarkable concentrating ability determined by fasting urine osmolality; (iii) normal creatinine clearance, and (iv) unremarkable ultrasonography to measure renal size and to screen for nephrocalcinosis or nephrolithiasis. Although no significant renal compromise was detected with these studies in our hypercalciuric pediatric OI patients, investigation of affected adults, especially those severely affected, will be important to assess whether this is a long-term problem and if adverse effects on the kidneys do develop. PMID- 7786639 TI - Parathyroid hormone restores bone mass and enhances osteoblast insulin-like growth factor I gene expression in ovariectomized rats. AB - In the osteopenic rat model, estrogen deficiency results in increased bone turnover with net bone loss occurring during cancellous modeling. However, estrogen-deficient rats treated with parathyroid hormone (PTH) experience a net gain of bone tissue due to the anabolic effects of PTH. To evaluate the possibility that local insulinlike growth factor I (IGF-I) production modulates the in vivo balance of bone formation and resorption in ovariectomized (OVX) estrogen-deficient rats and in OVX rats treated with PTH, we have studied the expression of IGF-I mRNA in cancellous bone osteoblasts using in situ hybridization techniques. Three-month-old virgin rats were subjected to sham surgery or OVX. Two weeks later, half the OVX rats began treatment with hPTH(1 34), 5 micrograms/100 g body weight, 5 days/week for 4 weeks. All animals were killed at the same time, providing three groups: sham surgery alone; OVX alone; and OVX + PTH. Bone histomorphometry performed in undecalcified sections of tibial metaphysis confirmed that OVX rats had significantly (p < 0.05) increased bone surface formation rates (BFR/BS, micron 3/micron 2/year) with osteopenia while OVX + PTH rats had increased BFR/BS with increased bone volumes compared to sham animals (p < 0.05). Decalcified tissue from all three groups contained immunoreactive IGF-I. Similar tissue sections were hybridized with an 35S-labeled IGF-I antisense riboprobe. Evaluation of the specific signal over cancellous osteoblasts allowed a relative estimate of IGF-I mRNA transcript abundance in the three groups by counting silver grains per osteoblast, corrected for background activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786638 TI - Bone resorption induced by a metastatic human melanoma cell line. AB - Bone resorption resulting from the metastatic human melanoma cell line (A375) was investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 (1 x 10(5)) in the left ventricle produced multiple osteolytic lesions. Many TRAPase-positive multinucleated cells, identified by EM as osteoclasts, were observed on the bone surface at the site of metastases. The findings suggest that bone resorption was caused by osteoclasts developed in the presence of tumor cells. Even where tumor cells were juxtaposed to bone surface, small and flat TRAPase-positive cells were shown to exist on the bone surface. Thus, bone resorption was mainly associated with the occurrence of osteoclasts. A large number of osteoclast progenitor cells were also observed adjacent to tumor cells and/or stromal cells located apart from bone, indicating possible participation of tumor cells and/or stromal cells in the differentiation of osteoclasts. Ultrastructurally, stromal cells and/or extracellular matrices were present between tumor cells and osteoclast progenitor cells. Immunohistochemical observation clarified the localization of heparan sulfate proteoglycan (HSPG) and fibronectin (FN) around osteoclast progenitor cells. These findings suggest that they play an important role in providing a microenvironment favorable for osteoclast differentiation and activation. The immunohistochemical localization of IL-6, PGE2, and TGF-alpha also indicates that they are involved in osteoclast differentiation and activation. In conclusion, bone resorption at the metastatic sites of A375 is mediated via osteoclasts and A375 cells may be involved in the differentiation and activation of osteoclasts in association with stromal cells, extracellular matrices (HSPG, FN) and osteotropic cytokines (IL-6, PGE2, TGF-alpha). PMID- 7786640 TI - Effects of basic fibroblast growth factor (bFGF) on bone formation in growing rats. AB - The effects of basic fibroblasts growth factor (bFGF) administered intravenously at dosages of 0.1 and 0.3 mg/kg per day for 7 days to growing rats are reported. Static and dynamic histomorphometry techniques were applied to the microradiographs and undecalcified ground sections of the proximal tibiae and tibial shafts. The bone histomorphometric analyses in the proximal tibia revealed that 0.1 mg/kg per day of bFGF increased longitudinal growth rate, cartilage cell production rate, and metaphyseal bone area. In the tibial shaft, the endocortical mineral apposition and bone formation rates, total bone area, total osteoid area, and medullary bone area were increased, but the periosteal mineral apposition and bone formation rates were depressed. Two weeks after the cessation of treatment, the increased osteoid bone on the endocortical surface and in the marrow cavity was completely calcified, and the total mineralized area in the tibial shaft was significantly increased. The rats given 0.3 mg of bFGF/kg per day showed retarded weight gain, defective calcification at the growth plate metaphyseal junction, and on the endocortical surface. The growth plate width was increased, and the longitudinal growth rate, cartilage cell production rate, endocortical labeled surface, and bone formation rate were decreased. Two weeks after the cessation of treatment, these changes were almost reversed, and the longitudinal growth rate and cartilage cell production rate were increased as rebound phenomena. These results suggest that a low dose (0.1 mg/kg per day) of bFGF stimulates endosteal and endochondral bone formation and depresses periosteal bone formation in growing rats. PMID- 7786641 TI - Cortical mineral content of the radius assessed by peripheral QCT predicts compressive strength on biomechanical testing. AB - Our aim was to evaluate the role of cortical bone in resistance to compression in the human radius. Thirty-three left cadaver forearms were scanned on an XCT 960 Stratec CT scanner. Cortical density and cortical thickness were measured at the junction of the middle and distal third of the radius. Subsequently, 2-cm-high cylindrical specimens, centrated on the level of the CT slice, were cut. After removal of the endosteal trabecular bone, the specimens were submitted to compressive testing, using an Instron machine, and load deformation curves were obtained. Maximal stress (load corrected for cross-sectional area) showed a significant relationship with the density (r = 0.78) as well as with the thickness (r = 0.74) of the cortex. The closest correlation involved the maximal load and the mineral content of the cortex specimens (r = 0.87). We conclude that the mineral content of these radius cortex specimens, measured using peripheral QCT, predicts their compressive strength on biomechanical testing. PMID- 7786642 TI - Validation of wall thickness estimates obtained with polarized light microscopy using multiple fluorochrome labels: correlation with erosion depth estimates obtained by lamellar counting. AB - Numerous methods are currently being employed to estimate completed wall thickness and final erosion depth. Conflicting estimates of calculated bone balance have been obtained from the estimates of wall thickness and erosion depth using these various methods. To assess the utility of two specific methods to estimate wall thickness (polarized microscopy) and erosion depth (lamellar counts), we conducted a study in normal young adult beagle dogs, a model where bone balance should approximate 0. Dogs were administered multiple fluorochrome labels in vivo to label activity forming bone pockets. These labels were used to confirm the position of the cement line of the bone structural unit (BSU) in fluorescent light. Parallel measurements of wall thickness were then collected in polarized light. These estimates were compared to estimates of erosion depth obtained by lamellar counting and bone balance was calculated. Estimates of wall thickness correlated well with estimates of erosion depth with bone balance not differing significantly from 0. These data suggest that the combination of these two methods is a reasonable approach to obtaining estimates of bone balance at the level of the remodeling unit. PMID- 7786643 TI - Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements. AB - Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786644 TI - ACE inhibitors after myocardial infarction: selection and treatment for all. PMID- 7786646 TI - Medical devices: new regulations, new responsibilities. PMID- 7786645 TI - ACE inhibitors after myocardial infarction: patient selection or treatment for all? PMID- 7786647 TI - Primary angioplasty in myocardial infarction. PMID- 7786648 TI - Primary angioplasty is the most effective treatment for an acute myocardial infarction. PMID- 7786651 TI - Limitations of primary angioplasty in acute myocardial infarction. PMID- 7786650 TI - Immediate angioplasty: a conservative view from Europe. PMID- 7786652 TI - Primary angioplasty in a community hospital in the USA. PMID- 7786649 TI - Primary angioplasty. PMID- 7786653 TI - Immediate angioplasty in the United Kingdom. PMID- 7786654 TI - Experience of primary angioplasty in the United Kingdom. PMID- 7786656 TI - Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction. AB - OBJECTIVE: To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD: Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS: The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS: These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment. PMID- 7786655 TI - Familial dilated cardiomyopathy in the United Kingdom. AB - OBJECTIVES: To determine the frequency and mode of inheritance of familial dilated cardiomyopathy in the United Kingdom. BACKGROUND: Two recent prospective studies have suggested that familial forms of dilated cardiomyopathy are common but have been limited by selective screening methods, inadequate diagnostic criteria, and low rates of ascertainment. METHODS: Prospective screening study of 236 relatives from 40 families of patients with dilated cardiomyopathy. Screening consisted of clinical examination, 12 lead electrocardiogram, and two-dimensional Doppler echocardiography. Relatives with systemic hypertension and other cardiac diseases were excluded from the study. All echocardiograms were performed by an experienced echocardiographer who was blinded to clinical information. Relatives were classified as having dilated cardiomyopathy, left ventricular enlargement (method of Henry), depressed fractional shortening, or as being normal. Relatives with abnormal investigations underwent further evaluation as appropriate. RESULTS: Twenty five cases of dilated cardiomyopathy were identified and came from 10 (25%) of the 40 families screened. Pedigree analysis was most consistent with autosomal dominant inheritance and variable penetrance (65-95%). Of the remaining apparently healthy relatives, 37 (18%) were found to have left ventricular enlargement and nine (4%) depressed fractional shortening; these values were significantly higher than those observed in 239 healthy controls (24 (10%), P = 0.02 and one (0.4%), P = 0.01, respectively). CONCLUSIONS: Patients with dilated cardiomyopathy commonly have an affected family member and a high proportion of apparently healthy relatives with minor echocardiographic abnormalities. Segregation analysis suggests that familial dilated cardiomyopathy is the result of the transmission of a rare autosomal dominant gene. Further studies are currently underway to characterise the molecular basis of familial dilated cardiomyopathy and identify early disease within these families. PMID- 7786657 TI - Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. AB - OBJECTIVE: To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. PATIENTS AND DESIGN: 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. METHODS: Patients aged 18 75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. RESULTS: Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. CONCLUSION: Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure. PMID- 7786659 TI - Change in delay of atrioventricular conduction after radiofrequency catheter ablation for atrioventricular nodal re-entry tachycardia. AB - OBJECTIVE: To monitor atrioventricular conduction after radiofrequency ablation for atrioventricular nodal re-entry tachycardia. DESIGN: Measurement of PR interval from 12 lead surface electrocardiograms before; at 0, 24, 48, 72, and 96 hours; and at 1 and 6 months after radiofrequency ablation. PATIENTS: 40 consecutive patients with atrioventricular nodal re-entry tachycardia. The anterior approach was used in 23 patients, the posterior approach in 17. RESULTS: With the anterior approach the PR interval increased significantly and progressively until 48 hours after ablation (maximum 282 (SD 62.2) ms, before ablation 142 (29.5) ms; P < 0.0001). Up to 96 hours no further change was observed, but one month after ablation the PR interval had decreased to a value not significantly different from that 24 hours after the procedure (231 (51.2) ms). In one patient total atrioventricular block developed 24 hours after an uncomplicated procedure and a permanent pacemaker was implanted. With the posterior approach the PR interval increased slightly in the first 24 hours (156 (22.7) ms, before ablation 144 (21.2) ms P = 0.004), but it had returned to preablation values at 1 month. One patient developed second degree atrioventricular block during the first 24 hours after ablation, despite delivery of all radiofrequency pulses posterior to Koch's triangle at sites without His bundle deflection. PR intervals at 6 months did not differ significantly from the values at 1 month. CONCLUSION: After the anterior approach the progressive delay in atrioventricular conduction up to 48 hours after radiofrequency ablation for atrioventricular nodal re-entry tachycardia warrants continuous in hospital monitoring of patients for at least two days after the procedure. PMID- 7786658 TI - Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril. AB - OBJECTIVES: To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. DESIGN: Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by "open" intravenous infusion of prostaglandin E2 (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before "open" captopril (study B). METHODS: Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E2 was measured by radioimmunoassay. SETTING: University department of cardiovascular medicine. PATIENTS: 12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors. RESULTS: Indomethacin resulted in adverse effects on cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration, urinary sodium excretion, and calf vascular resistance. Changes were reversed with infusion of prostaglandin E2. Pretreatment with indomethacin resulted in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril. Similarly, an increase in renal blood flow with captopril was attenuated by indomethacin. CONCLUSIONS: The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostaglandins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure. The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostaglandin synthesis. PMID- 7786660 TI - Ventilatory responses to exercise in adults after repair of tetralogy of Fallot. AB - BACKGROUND: Adult patients with total correction of tetralogy of Fallot may have poor exercise capacity associated with impaired right heart function and in particular pulmonary regurgitation. The ventilatory responses to exercise were studied in a group of such patients to assess relations between ventilation, exercise capacity, and right ventricular function. METHODS: 30 patients (7 female) (aged 27.8 (6.0) years) and 30 (7 female) controls of a similar age range were studied prospectively. All underwent exercise testing with metabolic gas exchange to determine peak oxygen consumption (peak VO2), and (as indices of the ventilatory response) the slope of the relation between both respiratory rate (RR) and ventilation (VE) against carbon dioxide production (VCO2). Patients were studied with pulsed wave Doppler echocardiography to determine pulmonary arterial systolic and diastolic flow characteristics. Patients were defined as having restrictive right ventricular function where diastolic pulmonary forward flow was seen coincident with atrial systole. RESULTS: In the group with tetralogy of Fallot mean (SD) peak VO2 was 35.3 (7.5) ml/kg/min (93.6 (15.3) % of expected for age, weight, height and sex). The RR/VCO2 slope was steeper in the Fallot group (6.8 (2.6) v 9.6 (4.7), P < 0.02). Those with restrictive right ventricles achieved a higher peak VO2 than those without (82.5 (10.1) % v 100.9 (13.8), P < 0.001). In the Fallot group alone, there was an inverse relation between ventilatory response and peak VO2 (RR/VCO2 v peak VO2; r = -0.63, P = 0.003: VE/VCO2 v peak VO2; r = -0.62, P < 0.001). CONCLUSIONS: Many of these patients with repaired tetralogy of Fallot had near normal exercise capacity, but as exercise capacity decreased, the ventilatory response to exercise increased. This was not due to alterations in pulmonary function tests or to the effects of cardiac size causing decreased lung volume. It may be that the increased ventilatory rate at a given level of carbon dioxide production acts as a respiratory pump aiding right ventricular function. PMID- 7786662 TI - High wall shear stress proximal to myocardial bridging and atherosclerosis: intracoronary ultrasound and pressure measurements. AB - BACKGROUND: Studies have shown that myocardial bridging may prevent coronary atherosclerosis and that the segment proximal to the bridge is often sclerosed. The underlying mechanism is still unknown. METHODS: Intracoronary ultrasound and pressure measurements were performed in a patient with myocardial bridging in the left anterior descending coronary artery. A 3.5 F, 20 MHz probe was used to measure the change in cross sectional area of the lumen during the cardiac cycle. Intracoronary pressure was measured with a Double tip, end mounted pressure transducer system, the catheter having two pressure sensors located at the end of the catheter 3 cm apart. Intracoronary pressure was recorded as the catheter was slowly advanced and pulled back through the left anterior descending coronary artery. RESULTS: Systolic compression of the bridge segment was clearly visualised on ultrasonography and an eccentric plaque with calcium deposit was found in the segment proximal to the bridge. The pressure in the segment proximal to the bridge (160/26 mm Hg) was higher than that of the proximal normal segment (126/68 mm Hg). The pressure distal to the bridge was 68/30 mm Hg. A highly characteristic "sucking effect" was found in the bridge segment. The pressure in the bridge segment was 102/-40 mm Hg. CONCLUSION: The pressure in the segment proximal to the myocardial bridging was higher than aortic pressure. Disturbance of blood flow and high wall stress proximal to myocardial bridging was a main contributor to the development of atherosclerosis in the segment proximal to the bridge. PMID- 7786661 TI - Effects of type 1 diabetes mellitus on cardiac function: a study of monozygotic twins. AB - OBJECTIVE: To investigate left ventricular size and function in type 1 diabetes and their relation with diabetes duration, glycaemic control, autonomic dysfunction, and complications of diabetes. DESIGN: Cross sectional study using a pulsed wave Doppler echocardiogram to assess left ventricular dimensions, wall thickness, and transmitral blood flow velocity signals. PATIENTS: 40 monozygotic twin pairs (23 male, mean age 26 years) discordant for type 1 diabetes and 40 non diabetic singleton controls with no clinical evidence of cardiac ischaemia. RESULTS: For all Doppler echocardiographic measurements there were strong correlations between monozygotic twins but not between twins and control subjects. Left ventricular dimensions, wall thickness and systolic function, peak E velocity, and the velocity integrals of early left ventricular filling were similar in all three groups. Peak A velocity and the velocity integrals of late ventricular filling (mean (SD)) were greater in diabetic twins (45 (12) v 38 (8) cm/s, P = 0.002; and 32 (11) v 26 (6), P = 0.0002). Diabetic twins had lower E/A ratio (1.59 (0.39) v 1.83 (0.39), P < 0.001), greater atrial filling fraction to total diastolic filling (28 (6) v 25 (5)%, P = 0.002), and prolonged isovolumic relaxation time (72 (12) v 63 (9) ms, P < 0.001). The differences in Doppler findings between diabetic and non-diabetic twins were related to disease duration whereas the prolongation of the isovolumic relaxation time was related to cardiac autonomic dysfunction. CONCLUSIONS: These results show that twins with type 1 diabetes have left ventricular diastolic dysfunction related to diabetes duration and cardiac autonomic dysfunction but not to glycaemic control or microvascular complications. In addition, genetic factors contribute to left ventricular dimension and function. PMID- 7786663 TI - Do radionuclide and echocardiographic techniques give a universal cut off value for left ventricular ejection fraction that can be used to select patients for treatment with ACE inhibitors after myocardial infarction? AB - OBJECTIVE: To determine whether echocardiography and radionuclide angiography give comparable results when the left ventricular ejection fraction is measured early after myocardial infarction and thus whether, irrespective of the method used, a single value for the ejection fraction could be used as a guide for starting treatment with an angiotensin converting enzyme inhibitor. DESIGN: Prospective comparison of measurement of left ventricular ejection fraction by echocardiography and radionuclide angiography. SETTING: Coronary care units of two university teaching hospitals in Glasgow. PATIENTS: 99 patients studied within 36 hours of acute myocardial infarction. OUTCOME MEASURES: Left ventricular ejection fraction assessed by echocardiography and radionuclide angiography. RESULTS: 70 (77%) of the 99 patients had ejection fraction measured by both echocardiographic and radionuclide techniques, 30 in centre 1 and 40 in centre 2. In centre 1 the mean difference (SD) in ejection fraction (radionuclide angiography--echocardiography) was -8 (10%); 95% CI -12 to -4%. In centre 2 the mean difference was -14 (11%); 95% CI -17 to -11%. If patients had been treated with an ACE inhibitor on the basis of a radionuclide ejection fraction of < 40% then 93% in centre 1 (28 of 30) and 98% in centre 2 (39 of 40) would have been treated. This compares with 63% (19 of 30) and 50% (20 of 40), respectively if echocardiography had been used as a guide. CONCLUSION: Measurement of ejection fraction is highly dependent on the method used and it is therefore impossible to quote a universally applicable figure for left ventricular ejection fraction below which an ACE inhibitor should be used after myocardial infarction. PMID- 7786664 TI - ACE for whom? Implications for clinical practice of post-infarct trials. AB - OBJECTIVE: To determine how many lives would be saved if patients were routinely treated with ACE inhibitors after myocardial infarction according to the criteria of four recent major clinical trials, and to estimate the costs and benefits of these approaches. DESIGN: Retrospective survey. SETTING: The Nottingham Health District. PATIENTS: Data from 7855 patients admitted between 1989 and 1990 were combined and the selection criteria of four major clinical trials (AIRE, SAVE, GISSI-3, and ISIS-4) were applied. RESULTS: Of the patients admitted in Nottingham with confirmed myocardial infarcts 39% were eligible for AIRE and 8% for SAVE. In patients with suspected myocardial infarction as defined by the major trials, 60% would have been eligible for GISSI-3 and 63% for ISIS-4. Treating appropriate patients in accordance with these trials would have saved 20 (AIRE), 3 (SAVE), 4 (GISSI-3) and 5 (ISIS-4) lives each year in Nottingham at a drug cost of 5400 pounds, 33 pounds 791, 2730 pounds, and 4116 pounds per life per year saved respectively. CONCLUSIONS: Short-term treatment with ACE inhibition appears to be cheaper but such an approach would save fewer lives. The AIRE study is the most applicable to current clinical practice but ACE inhibitors should be offered routinely to patients satisfying the criteria of any of the four major clinical trials. PMID- 7786665 TI - Permanent pacemaker practice at a Scottish district general hospital between 1987 and 1993. AB - BACKGROUND: Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. It has been argued that the British public would be better served by a less centralised pacing service. There also exists the view, however, that a lower rate of complications and best follow up practice are achieved by specialised centres. The pacemaker practice over a 79 month period (January 1987 to July 1993) was thus reviewed with these issues in mind. METHODS: The pacemaker records of all new implantations for the period under observation were reviewed retrospectively. Data were acquired under the headings age, sex, symptoms, electrocardiographic (ECG) indications, and complications (early and late). Comparison was made with United Kingdom national data, a previous audit from Raigmore, and two recently published large series from specialist centres (one British and the other French). RESULTS: The mean age of patients who underwent implantation was 74 years and 47.5% were male. The most common presenting symptoms were syncope (46%), dizzy spells (24.5%), and heart failure (11.5%). The most common ECG indications for pacing were complete heart block (wide QRS) (28%), atrial flutter/fibrillation with bradycardia (21.6%) and complete heart block (narrow QRS) (9.6%). The implantation rate was 184/million population/year in 1993. The early and late complication rates were low (2.48%). CONCLUSIONS: The presence of a pacing centre in a remote part of the United Kingdom fulfils a necessary service and has low complication rates, with implantation rates and patterns that are comparable with those in other parts of the country. PMID- 7786666 TI - Combined atrial and arterial switch procedure for congenital corrected transposition with ventricular septal defect. AB - OBJECTIVES: A combined atrial and arterial switch procedure was performed in selected patients with congenitally corrected transposition to establish the morphological left ventricle as the systemic ventricle. Immediate and early follow up results are presented. BACKGROUND: Progressive right ventricular dysfunction and tricuspid regurgitation are common in patients with congenitally corrected transposition who undergo repair of associated lesions. A surgical procedure which re-establishes the left ventricle as the systemic ventricle should improve functional results. METHODS: Four symptomatic children aged from 9 months to 3 years 1 month (mean 2 years 3 months) with congenitally corrected transposition and ventricular septal defect underwent both an atrial and arterial switch procedure and were followed up for a mean of 12 months (range 6-21 months). RESULTS: There were no early or late deaths. Conduction abnormalities worsened in two patients. Hospital stay ranged from 8 to 17 days (mean 13 days). The cardiothoracic ratio decreased from a mean (range) of 0.65 (0.6 to 0.71) to 0.58 (0.52 to 0.6). Currently, three patients are in functional class I and one child is in functional class II. CONCLUSIONS: The combination of an atrial and an arterial switch procedure in symptomatic children with congenitally corrected transposition establishes the left ventricle as the systemic ventricle. The initial experience is encouraging with excellent immediate and early follow up results. PMID- 7786667 TI - Systemic thromboembolism leading to myocardial infarction and stroke after fenestrated total cavopulmonary connection. AB - Thromboembolic phenomena involving the caval veins, right atrium, and pulmonary artery are recognised complications after the Fontan operation and other forms of total cavopulmonary connection. A rare case of systemic thromboembolism is reported in a 3 year old girl who had repeated coronary and cerebral thromboembolic events after a fenestrated total cavopulmonary shunt operation. A survey of the 18 paediatric cardiac units in the United Kingdom and Ireland showed a wide discrepancy in anticoagulation policies after Fontan-type operations. Prevention of thrombotic complications by lifelong postoperative anticoagulation may outweigh the risk of haemorrhage. PMID- 7786669 TI - Increase in plasma beta endorphins precedes vasodepressor syncope. PMID- 7786670 TI - Nocturnal hypoxaemia after myocardial infarction. PMID- 7786671 TI - British Cardiac Society annual meeting. North Yorkshire, 23-25 May 1995. Abstracts. PMID- 7786668 TI - Reversal of haemochromatotic cardiomyopathy in beta thalassaemia by chelation therapy. AB - Haemochromatotic cardiomyopathy is the main cause of morbidity and mortality in patients with beta thalassaemia major. Once congestive heart failure develops most patients die in a few months. Congestive heart failure was reversed and echocardiographic findings were restored to normal in a 24 year old woman with beta thalassaemia who resumed treatment with chelation therapy (desferrioxamine). PMID- 7786673 TI - [Modification of the Furnas-Vilkki technic in the reconstruction of congenital or traumatic carpal hands]. AB - A technique is described for reconstruction of a pincer, by a second toe transfer, in traumatic and congenital deformities, leaving only the wrist. Transfer on the anterior aspect of the radius allows to benefit from the wrist mobility to compensate for the limited range of motion of the second toe. Proximal situation of the toe gives the possibility of harvesting plenty of tendons to balance the toe. Results have been encouraging in two traumatic and 6 congenital cases of peromelic type of symbrachydactyly. PMID- 7786672 TI - [The "die punch" operation in the sequellae of articular fractures of the radius]. PMID- 7786674 TI - [The prognosis of algodystrophic syndrome of the hand. Late results in 47 patients]. PMID- 7786675 TI - [A psychological approach to patients undergoing ambulatory surgery]. AB - 200 patients undergoing outpatient hand surgery were included in a sociological and psychological study. Certain points were found to be important: structure adapted to outpatient surgery, a single team, availability of the surgeon 24 hours a day, telephone call on the day after the operation, etc. Only 0.5% of operated patients claimed to be unhappy with their outpatient experience, but 2.5% would have preferred admission to hospital (for comfort reasons). Overall, outpatient procedures make the patient and his family responsible, by stimulating his cooperation and avoiding regression and dependence, frequently encountered in conventional hospitalization. Psychoanalysis has an important place in the pre- and postoperative approach to the patient. PMID- 7786679 TI - [A salvage technic: the "parrot" surgery]. PMID- 7786677 TI - [A comparative study of metacarpal resection and translocation after amputation of the middle finger]. AB - The authors studied 43 patients having sustained an amputation of one middle finger treated either by simple ray resection or translocation. The index-middle translocation was followed by more minor postoperative complications compared to all other techniques. A global score, taking into account daily activities, cosmetic result lack of mobility, residual pain, decreased strength, time off work, and return to work gave 131 points for simple third ray resection compare to index middle translocation (-252 points). Surprisingly, reduction of hand span on X ray study was minimal but strength was not correlated and translocation gave better strength, and therefore appears to be more appropriate for manual workers. For ring amputation, the score was definitely better for Leviet translocation with intracarpal osteotomy (143 points versus -36 for simple ray resection). However, the only drawback is more frequent (but minor) residual pain. PMID- 7786678 TI - [Vasomotor disorders of the hand and carpal tunnel syndrome]. AB - Clinical electrophysiological and chronothermodynamic examinations were performed on 71 patients with paresthesiae and pain of the hands. In 35 patients, the electromyographic examination confirmed the diagnosis of carpal tunnel syndrome on the basis of clear signs of chronic compression of the median nerve at the carpal tunnel. In the other 36 patients, the electro-physiological findings were normal. Twenty-nine patients with bilateral (n = 24) or unilateral (n = 5) carpal tunnel syndrome, and 29 patients without, this syndrome had chronothermodynamic abnormalities demonstrating the vascular origin of the disorders of the hands; in 18 patients, a Raynaud's syndrome was suspected on the basis of severe dysthermia. In 7 patients, the origin of pain and paresthesiae remained unknown. This study shows that (i) vascular disorders of the hand are very frequent in patients with paresthesiae and pain of the hands and may mimic a carpal tunnel syndrome, and (ii) clinical examination is insufficient to assess the diagnosis of carpal tunnel syndrome. Before deciding on any kind of therapy, this diagnosis has to be assessed on electrophysiological and chronothermodynamic examinations performed according to precise protocols. PMID- 7786676 TI - [Results of flexor tendon repair using the Tsuge technic. Apropos of a series of 95 fingers]. AB - The authors review a series of 76 patients with 95 fingers involved, 66.6% of them occurring in zone II. The core stitch was performed according to the Tsuge technique (type II) combined with a peritendinous running suture. Results based on TAM were excellent or good in 60%, fair in 22%, and poor in 18%. Influencing factors were associated lesions, mainly vascular and lesions in zone II. Rupture occurred in 5% and adhesion in 22% of cases. Providing similar results to those of other techniques published in the current literature, the Tsuge techniques is preferred because it is simpler and faster to perform. PMID- 7786681 TI - Magnesium and lithium antagonism of carbachol- and electrically-induced smooth muscle contractions in the rat gastrointestinal tract. AB - The pharmacological actions of lithium and magnesium have been investigated using isolated smooth muscle preparations from the rat gastrointestinal tract. Tissue contraction was evoked by means of carbachol or electrical field stimulation and the degree of inhibition of contraction caused by lithium was measured. Lithium effects were compared with those of the chemically similar ions, magnesium and calcium, by manipulation of the physiological buffer solutions. Lithium antagonism was enhanced when tissue contractile mechanisms were dependent on extracellular calcium concentration in the bathing fluid. This suggests that lithium is acting at the cell membrane by preventing calcium entry via ion channels. These results are consistent with evidence from clinical studies which indicate low cellular accumulation of lithium at therapeutic concentrations. PMID- 7786680 TI - European Association of Cardiothoracic Anaesthesiologists 10th annual meeting. Madrid, Spain, 15-17 June 1995. Abstracts. PMID- 7786682 TI - Effects of extracellular magnesium and beta adrenergic stimulation on contractile force and magnesium mobilization in the isolated rat heart. AB - This study investigates the metabolism of the divalent cation, magnesium (Mg2+) in the isolated perfused Langendorff's rat heart and ventricular slices in the absence and presence of catecholamines including isoprenaline, noradrenaline and adrenaline. Perfusion of the isolated rat heart with a physiological salt solution containing elevated extracellular Mg2+ [Mg2+]o (2.4 mM-6.0 mM) resulted in a marked and progressive decrease in the amplitude of contraction compared to control [Mg2+]o (1.2 mM). In contrast, perfusion of hearts with low (0-0.6 mM) [Mg2+]o caused a small transient increase in the amplitude of contraction which was often accompanied by arrhythmic activity. Perfusion of the heart with a nominally Mg2+ free medium resulted in a time-dependent net efflux of Mg2+ reaching a steady state after approximately 40-50 min of perfusion. This release of Mg2+ was associated with a concurrent decrease in total heart Mg2+. Stimulation of the heart with the beta adrenergic agonist, isoprenaline (10(-7) M) caused large increases in net Mg2+ efflux which was associated with marked increased in both rate and the amplitude of contraction. Similar effects on Mg2+ efflux were also observed during perfusion of the heart with the adenylate cyclase activator, forskolin (10(-5) M). Superfusion of paced ventricular segments with either isoprenaline, adrenaline or noradrenaline (all 10(-6) M) also resulted in a marked transient net efflux of Mg2+. Pre-treatment of segments with the beta adrenergic antagonist, propranolol (10(-5) M) competitively blocked the Mg2+ efflux evoked by the catecholamines. Similarly, pre-treatment of segments with the calcium (Ca2+) channel blocker, verapamil (10(-5) M) caused a significant (P < 0.05) decrease in net Mg2+ efflux evoked by isoprenaline. The results of this study indicate that (1) the perturbation of [Mg2+]o has an important influence on myocardial contractility and (2) the mobilization of Mg2+ in the heart is associated with beta adrenergic stimulation possibly via an elevation in intracellular adenosine 3.5 cyclic monophosphate (cyclic AMP). PMID- 7786683 TI - Enhanced contractile response to phenylephrine and increased density of [3H]PN200 110 binding sites in thoracic aorta isolated from dietary magnesium-deficient rats. AB - The present study was undertaken to examine whether the enhanced contractile response to phenylephrine observed in thoracic aorta isolated from dietary magnesium-deficient rats depends on an increased density of alpha 1-adrenoceptor or calcium channels. Adult male Wistar rats were fed with a magnesium-deficient diet (0.001 per cent magnesium) for 30 days with control groups (0.07 per cent magnesium). The contractile response to phenylephrine was significantly inhibited by nifedipine in both aortas without endothelium, and the degree of the inhibition was significantly greater in magnesium-deficient rats than in controls. Membranes were isolated from both thoracic aortas without endothelium, and the binding of [3H]PN200-110 or [3H]prazosin to the membranes was studied. A single binding site for [3H]PN200-110 or [3H]prazosin was evident for both membranes with high affinity. Dietary magnesium-deficiency increased significantly the maximal number (Bmax) of [3H]PN200-110 binding sites, but not Bmax of [3H]prazosin, and did not alter the binding affinity of both ligands. These results suggest that increased density of calcium channels participates in the enhanced contractile response to phenylephrine in thoracic aortas isolated from dietary magnesium-deficient rats. PMID- 7786684 TI - Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function. AB - The cholesterol oxide (ChO) levels in the plasma and low density lipoproteins (LDL and VLDL) in four groups of rabbits fed for seven weeks either normal (NC) or high cholesterol (HC) with low or normal magnesium (Mg) diets were determined and compared with the NC group fed a standard rabbit diet. The plasma from the NC group contained low levels of different cholesterol oxides. These cholesterol oxides were significantly elevated in the plasma of rabbits fed a HC-normal magnesium or a HC-low magnesium diet. In the NC-low Mg group, 7 alpha hydroxycholesterol, 7 beta-hydroxycholesterol and 7-ketocholesterol were elevated while the other cholesterol oxides remained within the normal range of the NC group. When the cholesterol oxides were assayed in the LDL and VLDL fractions as micrograms/mg protein, the fractions obtained from the groups fed NC-low Mg, HC normal Mg or HC-low Mg diets showed higher levels of cholesterol oxides than the fractions obtained from the NC group. When LDL and VLDL fractions from the different groups were incubated at equal protein concentration with confluent endothelial cell monolayers, transendothelial albumin transfer was significantly increased by the lipoproteins from the experimental groups as compared to the control group. These results suggest that elevation of cholesterol oxides in magnesium deficiency or hypercholesterolaemia may be related to their atherogenic effects through decreasing the endothelial barrier function which could enhance the deposition of cholesterol rich lipoproteins into the arterial wall. PMID- 7786685 TI - Oestrogen but not testosterone increases bone density in orchiectomized rats more when fed moderately magnesium-deficient fructose than moderately magnesium deficient cornstarch. AB - To investigate interactions between circulating sex hormones, dietary fructose and magnesium on bone mineral density and numbers of trabeculae, 10 weeks old orchiectomized and sham-orchiectomized rats were studied. One-third of the orchiectomized animals were injected with beta-oestradiol-3-benzoate twice per week in sesame oil; another one-third, testosterone cypionate; the remaining one third as well as the sham-orchiectomized animals, sesame oil only. All animals were fed either fructose or cornstarch without added magnesium. After 14 weeks, a 24 h urine sample was collected for measurements of calcium, magnesium, phosphorus, and cAMP. Blood was collected for determinations of calcium, magnesium, phosphorus, 25-monohydroxy and 1,25-dihydroxycholecalciferols, oestrogen, testosterone, and parathyroid hormone. Femurs were used for measurements of bone mineral density, and tibiae, for numbers of trabeculae. Exogenous testosterone interacted with starch and magnesium deficiency to decrease serum calcium concentration significantly, which increased circulating parathyroid hormone. High circulating parathyroid hormone raised urinary cAMP and serum 1,25-dihydroxycholecalciferol. Increased parathyroid hormone, cAMP and 1,25 dihydroxycholecalciferol may be responsible for bone resorption which was noted in reductions of bone mineral density and the numbers of trabeculae in the group. In contrast, exogenous oestrogen interacted with fructose and magnesium deficiency to increase serum calcium concentration which caused a reduction of circulating parathyroid. Low parathyroid hormone, reduced 1,25 dihydroxycholecalciferol and cAMP may explain the increased bone mineral density and the numbers of trabeculae in this group. PMID- 7786686 TI - Influence of high and low dietary magnesium levels on functional, chemical and morphological parameters of 'old' rats. AB - The effect of dietary magnesium deficiency has so far been studied preferentially in rapidly growing rodents or in adult animals. Since magnesium deficiency frequently occurs in elderly persons too, magnesium- and calcium-deficient diets were offered during 32 and 64 days to 'old' rats (34 months old, spontaneous mortality of 15 per cent). The calcium-deficient diet (2.5 per cent of the requirement) was well tolerated and no profound biochemical disturbances were noted. In contrast, dietary magnesium deficiency (12.5 per cent of the requirement) induced loss of body weight, formation of erythema, severe hypomagnesaemia and increase of tissue calcium levels. No seizures were noted and mortality did not increase, in contrast to growing magnesium-deficient rats. Histologically, age effects were present in bone tissues of old rats, however no additional dietary effects became visible. Tensile strength of femur and rib did not reveal treatment-related changes. Fourteen days preloading with high dietary magnesium increased plasma magnesium and also skeletal concentrations, although to an only small degree. Nevertheless, time until the appearance of erythema in 50 per cent of the rats subsequently fed the magnesium-deficient diet was significantly delayed. PMID- 7786687 TI - Potentiation of magnesium-deficiency-induced foetotoxicity by concomitant iron deficiency and its prevention by adequate supply via drinking water. AB - Magnesium (Mg) and iron (Fe) deficiency frequently develop during pregnancy. Therefore these factors were studied alone (Mg-L, resp. Fe-L) or in combination (Mg-L/Fe-L) on 16 female and 8 male adult fertile Sprague-Dawley rats. The animals were offered a basal diet containing 30 per cent and 17 per cent of the rat's requirement for magnesium and iron, respectively, starting 21 days before mating (2:1) until 49 days after mating. Offspring were also kept on this regimen during a 3-week lactation period and 7 days post weaning. Drinking water was either enriched with 101 ppm Fe2+ (ferrous gluconate): Mg-L, or 365 ppm magnesium (magnesium-L-aspartate hydrochloride trihydrate, MAH): Fe-L, or with any: Mg-L/Fe L or with both electrolytes: Controls. Fertility remained unaffected under these conditions. Clinically, Fe-L induced iron deficiency and growth retardation of offspring. Pronounced reproductive toxicity was elicited by Mg-L and was even potentiated by Mg-L/Fe-L. In the parental generation, too, adverse effects of Mg L were aggravated by Mg-L/Fe-L despite the fact that no iron accumulation occurred. Bioavailability of iron was not impaired by magnesium as MAH. With respect to human pregnancy magnesium supplementation has higher priority over iron supplements. To improve tolerance and compliance both minerals are suggested to be taken simultaneously. PMID- 7786688 TI - Parenteral magnesium sulphate restores regional contractile function in the post ischaemic canine myocardium. AB - The effects of parenteral magnesium sulphate (MS) on the regional contractile response of stunned myocardium was examined in 45 pentobarbital anaesthetized dogs. The hearts were instrumented to measure left ventricular pressure (LVP), coronary flow velocity (CFV), mean arterial blood pressure (MAP), and regional contractile function (percent segment shortening, %S; and end-diastolic segment length, EDL). Stunning was produced by a 10 min occlusion of the first descending branch of the left circumflex coronary artery. Immediately upon release of the occlusion, either magnesium sulphate or a dextrose vehicle (D5W, n = 15) was infused. Magnesium sulphate was given intravenously (IV-MS, 100 mg/kg, n = 15) or intracoronarily (IC-MS, 1.5 mg/kg, n = 15). Coronary occlusion was consistently associated with significant decreases in coronary flow velocity and %S in all groups. Following IV-MS, heart rate (HR) and mean arterial blood pressure decreased significantly from preocclusion values, whereas end-diastolic segment length tended to increase and left ventricular pressure remained constant. IC-MS did not produce any changes in heart rate, mean arterial blood pressure, end- diastolic segment length or left ventricular pressure. At the end of the magnesium sulphate infusion (IV or IC), and for the next 60 min, %S returned to or above pre-occlusion values (P < 0.05 vs. D5W). Dyskinesia and hypokinesia were abolished in the magnesium sulphate groups, but were still present in the D5W group at the end of the 60 min period (P < 0.05 vs. pre-occlusion). We conclude that parenteral magnesium sulphate significantly improves regional contractile function in the stunned myocardium. Data from the IC-MS group would suggest a direct myocardial effect, independent of changes in preload, afterload, heart rate or flow. PMID- 7786689 TI - A prospective randomized trial of intravenous magnesium versus intravenous propranolol in acute myocardial infarction. AB - A total of 266 patients entered into a study comparing the effect of intravenous magnesium and propranolol following acute myocardial infarction. Of these, 97 were able to receive either drug and were therefore randomized into the magnesium (n = 51) or propranolol group (n = 46). 88 patients were unable to receive propranolol and formed a third group (NR) while a further 81 patients could not receive either drug and formed a fourth group (N). The study showed that intravenous magnesium was as effective in preventing potentially lethal arrhythmias as propranolol and could be given to some 70 per cent of such patients whereas propranolol could only be given to 36 per cent. PMID- 7786690 TI - Long-term follow-up after acute myocardial infarction in patients randomized to treatment with intravenous magnesium or intravenous propranolol in the acute phase. AB - Ninety-five patients with acute myocardial infarction were followed up for 6 months to 3 years (mean 25.4 months) in a preliminary study to compare the effects of intravenous magnesium (49 patients) with that of intravenous propranolol (44 patients) given immediately after admission to the intensive care unit. There were four cardiac deaths in the propranolol group and no deaths in the magnesium group (P < 0.046) and 27 per cent of patients who received propranolol subsequently developed cardiac failure as opposed to 12 per cent of those who had received magnesium (P < 0.04). Intravenous magnesium given in the early stages of myocardial infarction reduces the subsequent cardiac death rate possibly by reducing infarct size. PMID- 7786691 TI - Nutritional magnesium supplementation does not change blood pressure nor serum or muscle potassium and magnesium in untreated hypertension. A double-blind crossover study. AB - The aim of this study was to evaluate if a nutritional dose of magnesium given orally changes the blood pressure in untreated hypertensive patients and if orally-given magnesium had any influence on serum and muscle magnesium and potassium. A randomized, double-blind crossover study design was followed with magnesium 15 mmol/day or placebo treatment for two months. Thirty-nine patients aged 20-59 years, were treated. Samples for magnesium and potassium in blood, muscle and urine were taken at entry time, after two months (crossover time) and after four months (end of study). Systolic and diastolic supine and standing blood pressures were measured at the same times. No significant change in blood pressure, serum or muscle concentrations of electrolytes were observed on magnesium treatment. Urine magnesium rose significantly on magnesium, and it decreased significantly on placebo. Therefore results suggest that 15 mmol magnesium/day, given to untreated mild-to-moderate hypertensives does not alter blood pressure nor the concentrations of magnesium and potassium in serum and muscle, in patients with normal magnesium turnover. PMID- 7786692 TI - Selenium and magnesium status in fibromyalgia. AB - Muscle pain has been associated with magnesium (Mg) and selenium (Se) deficiency: magnesium and selenium status were investigated in fibromyalgia (FM). Erythrocyte (E), leucocyte (L) and serum (S) magnesium, serum selenium and zinc, and vitamin B1, B2, A or E status were assessed in 22 patients with fibromyalgia and in 23 age-matched healthy controls. LMg is significantly increased (P < 0.05) and EMg slightly decreased in fibromyalgia. These magnesium abnormalities are associated with previously-reported impairment of thiamin metabolism. Antioxidant status (as well as plasma malondialdehyde) is unchanged in fibromyalgia and serum selenium levels, slightly but not significantly correlated with serum magnesium, is normal. PMID- 7786693 TI - Magnesium status and parenteral magnesium sulphate therapy in acute aluminum phosphide intoxication. AB - The results of an open randomized study on magnesium status and parenteral magnesium sulphate therapy in acute aluminium phosphide intoxication are presented. The study was conducted on 105 patients divided into two group (I & II). Patients of Group I did not receive parenteral magnesium and acted as blank. Magnesium levels were monitored every 6 h for 24 h. Patients of group II received magnesium sulphate therapy. It was administered as 1.0 g (8.1 mEq or 4.05 mmol) magnesium sulphate dissolved in 100 ml of 5 per cent dextrose intravenously as a bolus dose followed by 1.0 g every hour for three successive hours, then 1.0 g every 6 h as a maintenance dose for the next 24 h as intravenous infusion in 5 per cent dextrose. The total dose of magnesium sulphate infused was 30.0 mmol over a period of 24 h (initial dose), then 16.0 mmol (4.0 g) daily till final outcome or a maximum of five days. All the vital parameters were monitored. All the patients were followed till final outcome. The resuscitation methods used were the same in both groups. At the end of the study, mortality rates were calculated in both groups. Hypomagnesaemia was observed as the constant finding in patients of Group I. It was transient and reversed itself without MgSO4. The mortality rate was 52 per cent. On the other hand, magnesium levels rose immediately after parenteral MgSO4 administration in patients of group II and they remained persistently above normal during the observed period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786694 TI - New concepts in the cardioprotective action of magnesium and taurine during the calcium paradox and ischaemia of the heart. AB - A rise in intracellular sodium during periods of exposure to calcium free media would seem to be the critical step that predisposes the mammalian heart to the damaging effects of the calcium paradox. The damage which is seen in both single cells and multicellular preparations, occurs on reperfusion with calcium containing media and results from calcium loading via the sodium/calcium exchanger where the rise in intracellular calcium provokes hypercontraction as well as activating hydrolytic enzymes. Because the rise in intracellular sodium is a critical step in inducing damage, manoeuvres which reduce this rise during calcium depletion are expected to protect the heart against the calcium paradox. Raising extracellular magnesium concentration is one such manoeuvre which by blocking the influx of sodium through the L-type calcium channels, reduces the rise in intracellular sodium during calcium depletion. The beta-amino acid taurine is another agent capable of opposing a rise in intracellular sodium. Taurine is present at high concentration in mammalian heart cells and is maintained against high concentration gradient. During calcium depletion, heart cells use this energy to efflux taurine and sodium via a taurine/sodium symport and therefore protect against the calcium paradox. A similar mechanism may also be used by the ischaemic heart to reduce the rise in intracellular sodium. In contrast to the changes seen during the calcium paradox the ischaemic heart shows a rise in intracellular magnesium concentration. This rise will have several and diverse cellular effects including the modulation of intracellular calcium mobilisation and of several membrane transporters. The potential significance of these effects remains to be evaluated. On the other hand elevated levels of extracellular magnesium may protect the ischaemic heart by reducing the influx of calcium by suppressing the L-type calcium channels and possibly the sodium/calcium exchanger. Finally evidence suggests that the rat heart may not be identical to that of other species in its response to the calcium paradox and to the protective role of intracellular taurine and extracellular magnesium. The reason for this species difference would seem to be due to different metabolic activity and the activity of the sodium, potassium-ATPase. PMID- 7786695 TI - Magnesium and therapeutics. AB - Two different types of therapy with magnesium are used: physiological oral magnesium supplementation which is totally atoxic since it palliates magnesium deficiencies by simply normalizing the magnesium intake and pharmacological magnesium therapy which may induce toxicity since it creates iatrogenic magnesium overload. Primary and secondary magnesium deficiencies constitute the sole indication of physiological oral magnesium therapy. It is therefore necessary to be well acquainted with the clinical and paraclinical pattern of magnesium deficit and to discriminate between magnesium deficiency due to an insufficient magnesium intake which only requires oral physiological supplementation and magnesium depletion related to a dysregulation of the control mechanisms of magnesium status which requires more or less specific regulation of its causal dysregulation. Physiological oral magnesium load constitutes the best tool for diagnosis of magnesium deficiency and the first step of its treatment. Physiological oral magnesium supplementation (5 mg/kg/day) is easy and can be carried out in the diet or with magnesium salts, with practically only one contra indication: overt renal failure. Specific and aspecific treatments of magnesium depletion are tricky using for example magnesium sparing diuretics, pharmacological doses of vitamin B6, physiological doses of vitamin D and of selenium. In order to use the pharmacological properties of induced therapeutic hypermagnesaemia, high oral doses of magnesium (> 10 mg/kg/day) are advisable for chronic indications and the parenteral route is suitable for acute indications. There are 3 types of indications: specific (for the treatment of some forms of magnesium deficit i.e. acute), pharmacological (i.e. without alterations of magnesium status) and mixed--pharmacological and aetiopathogenic--(for example complications of chronic alcoholism). Today pharmacological magnesium therapy mainly concerns the obstetrical, cardiological and anaesthesiological fields. The main indications are eclampsia, some dysrhythmias (torsades de pointe particularly) and myocardial ischaemias. But it is now difficult to situate the exact place of the pharmacological indications of magnesium. Magnesium infusions can only be envisaged in intensive care units with careful monitoring of pulse, arterial pressure, deep tendon reflexes, hourly diuresis, electrocardiogram and respiratory recordings. High oral magnesium doses besides their laxative action may bring latent complications which may reduce lifespan. There may remain some indications of the laxative and antacid properties of non soluble magnesium, particularly during intermittent haemodialysis. Lastly local use of the mucocutaneous and cytoprotective properties of magnesium is still valid, in cardioplegic solutions and for preservation of transplants particularly. PMID- 7786696 TI - Primary mitral valve prolapse: a clinical form of primary magnesium deficit. PMID- 7786697 TI - Early intravenous magnesium administration in acute myocardial infarction. PMID- 7786698 TI - Preliminary evaluation of a technique for inhibiting intimal hyperplasia: implantation of a resorbable luminal collagen membrane. AB - Pharmacologic control of intimal hyperplasia has been attempted through oral and intravenous administration of smooth muscle cell inhibitors. We report a more direct method of altering arterial healing using a novel bioresorbable membrane that can be applied to the lumen of an artery or anastomosis following endarterectomy or vascular reconstruction. Following a standard balloon injury, the infrarenal aortas of 3 kg female New Zealand white rabbits were opened and a thin membrane composed of collagen/chondroitin 6-sulfate copolymer was sutured to the posterior wall of each artery. Animals were killed at intervals of up to 3 months. All arteries remained patent. By 24 hours the membrane had become infiltrated with fibrin and red blood cells. An inflammatory response ensued and by 8 days the membrane was filled with mononuclear cells. At 3 months only a small remnant of the membrane remained. Intimal hyperplasia developed throughout the injured aorta. However, the hyperplastic response beneath the membrane was no greater than that observed in the adjacent injured aorta. A bioresorbable membrane can be sutured into the lumen of a small-diameter vessel without inducing thrombosis and without locally increasing intimal hyperplasia. A prosthesis of this type might be used to deliver inhibitors of smooth muscle cell proliferation and migration to the injured arterial wall. PMID- 7786699 TI - The effect of aging on the transarterial wall oxygen gradient. AB - Atherosclerosis is associated with aging based on numerous epidemiologic studies, whereas arterial wall hypoxia has been associated with other risk factors for atherosclerosis. We studied the effect of age on the transarterial wall oxygen gradient in the rat using an oxygen microelectrode. A decrease in oxygen tension in the outer 35% of the artery wall was noted in 36- to 40-week-old rats when compared to 3- to 4-week-old rats. These findings were noted despite no difference in arterial blood oxygen tension between the two groups and prior to any histologic evidence of atherosclerotic lesion formation. Our observations suggest that aging decreases the delivery of oxygen to the outer artery wall. PMID- 7786701 TI - Characteristics of patients at risk for perioperative myocardial infarction after infrainguinal bypass surgery: an exploratory study. AB - Patients requiring infrainguinal bypass surgery often have diffuse atherosclerotic disease, and perioperative myocardial infarction (MI) is a potentially lethal complication that is not uncommon in these patients. To establish additional clinical characteristics that might be useful in identifying patients who require more extensive cardiac evaluation, we conducted an exploratory case-control study comparing 22 patients who had a perioperative MI following elective infrainguinal bypass surgery with 191 control subjects whose bypasses were uneventful. In addition to previously recognized risk factors (e.g., history of angina or prior MI), we examined the association of perioperative MI with (1) results of common preoperative laboratory tests and ECG, (2) preoperative use of certain medications, and (3) intraoperative factors that might be anticipated prior to surgery (e.g., duration of surgery or type of anesthesia). Perioperative MI was associated not only with a history of angina, prior MI, or coronary artery disease but also with the need for certain cardiac medications, higher white blood cell (WBC) counts, ST-segment depression, left bundle branch block, and lengthy surgical procedures. Multiple logistic regression analysis identified the following factors as being independently associated with perioperative MI: preoperative antiarrhythmic agents (odds ratio [OR] = 26.4, p = 0.006), nitrates (OR = 8.4, p = 0.006), calcium channel blockers (OR = 5.5, p = 0.04), and aspirin (OR = 6.8, p < 0.01) and ST-segment depression (OR = 11.8, p = 0.01), WBC count (OR = 1.27/1000, p = 0.005), and duration of surgery (OR = 2.2/hr, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786700 TI - Early inflammatory response to gelatin- and collagen-sealed Dacron prostheses. AB - The immediate inflammatory response following aortic reconstruction with two types of sealed Dacron grafts was studied in a prospective, randomized manner. C reactive protein (CRP) levels were measured before surgery and on days 2 and 8 postoperatively. In the collagen-sealed group (n = 10) CRP levels were 10 +/- 9.6, 180.2 +/- 48.3, and 54.3 +/- 34.3 mg/L, respectively. In the gelatin impregnated group (n = 10) the values were 10.5 +/- 8.7, 200.7 +/- 27.3, and 80.3 +/- 30.2 mg/L, respectively. The slight differences were not significant according to the analysis of variance test for repeated measurements. These findings suggest that implantation of a knitted Dacron graft sealed with collagen does not lead to a higher inflammatory reaction compared with a gelatin-sealed graft. PMID- 7786703 TI - Is infrapopliteal bypass compromised by distal origin of the proximal anastomosis? AB - Distal origination of the proximal anastomosis (DOPA) of an infrapopliteal bypass beyond the adductor hiatus minimizes the length of graft required and optimizes use of scarce autogenous conduit. Sixty-two DOPA infrapopliteal revascularizations using autogenous vein performed for limb salvage over a 7-year period were reviewed and compared with 203 concurrent infrapopliteal bypasses originating more proximally (POPA). Life-table analysis revealed no difference at 54 months between DOPA and POPA bypass with regard to primary patency (57% vs. 50%, respectively) or secondary patency (67% vs. 65%, respectively). Differences in limb salvage at 54 months between DOPA and POPA bypasses did not reach statistical significance (53% vs. 66%, p = 0.12), although DOPA fared worse. Inferior limb salvage results in all infrapopliteal bypasses were correlated with the presence of tissue necrosis (52% vs. 70%, p < 0.001), which was more prevalent in patients undergoing DOPA bypass (71% vs. 49%, p < 0.01). The long term patency of infrapopliteal bypass appears only marginally affected by DOPA. However, the prognosis for limb salvage in this setting is compromised as a result of the virulent behavior of the atherosclerotic disease that spares the superficial femoral artery while predominantly involving the popliteal and tibial vessels. PMID- 7786704 TI - Intraoperative fibrinolytic therapy for salvage of limbs with acute arterial ischemia: an adjunct to thromboembolectomy. AB - The purpose of this prospective study was to determine the value of intraoperative intra-arterial fibrinolytic therapy (IIFT) in patients with acute arterial ischemia as an adjunct to mechanical thromboembolectomy. Sixty-six femoropopliteal or distal acute arterial occlusions were assessed by means of arteriography and Doppler imaging pre- and postoperatively. Two groups of patients were compared: one (n = 35) in which mechanical thromboembolectomy was applied as the single technique and another (n = 31) in which 250,000 IU of urokinase diluted in 250 ml of normal saline solution was instilled at the end of mechanical thromboembolectomy over a 30-minute period with the arterial inflow occluded. Candidates for IIFT were selected according to a nonrandomized method. Intraoperative arteriography showed residual thrombus in 20 (30.3%) patients and unsuspected arterial lesions in 23 (34.8%). Thrombosis recurrence was associated with residual thrombus (p < 0.001) and amputation (p < 0.001). The ankle/brachial index increased significantly (p < 0.05) in the patients who received IIFT (0.88 +/- 0.03) in comparison with those who underwent mechanical thromboembolectomy (0.75 +/- 0.05). Although the percentages of distal revascularization and amputation did not differ significantly between the two groups, quantitatively the results were better in the IIFT group (80.65% success and 9.68% failure) compared to the mechanical thromboembolectomy group (60% success and 22.86% failure). There was no bleeding due to IIFT. Significant variables in our study were diabetes (p < 0.05), the time period of 12 to 24 hours before the surgery (p < 0.05), and the severity of the ischemia in association with rest pain (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786702 TI - Hemodynamics of stenotic infrainguinal vein grafts: theoretic considerations. AB - We developed a theoretic model of arterial stenosis to study the relationship between perfusion pressure and regional hemodynamics in stenotic infrainguinal vein grafts in an attempt to identify grafts at high risk for failure. Our model was based on the concept of energy and mass conservation of the flowing blood. We used the modified Bernoulli equation (delta P = 4 delta V2) to calculate the maximum possible intrastenotic peak systolic velocity (PSV) from the systolic blood pressure. PSV was measured by means of duplex ultrasonography in infrainguinal bypasses up to the time of revision (nine grafts) or spontaneous thrombosis (two grafts). We related arm systolic blood pressure, intrastenotic PSV, and prestenotic PSV obtained from duplex examinations conducted prior to graft thrombosis or revision and applied our model to these stenotic vein grafts. Intrastenotic PSV was consistently lower than maximum PSV predicted from the Bernoulli equation. The highest measured intrastenotic PSV of 600 cm/sec would require a minimum perfusion pressure of 144 mm Hg. The lowest measured PSV (20 cm/sec) was considered the minimum "thrombotic threshold velocity." This model predicts that for parabolic profile flow in an 80% diameter-reducing axisymmetric stenosis (96% cross-sectional area reduction), a prestenotic PSV of 20 cm/sec would produce an intrastenotic PSV of 500 cm/sec requiring the equivalent potential energy of 100 mm Hg systolic blood pressure. Our theory implies that in patients with nocturnal hypotension thrombosis of stenotic vein grafts may occur. PMID- 7786705 TI - Infrapopliteal polytetrafluoroethylene and composite bypass: factors influencing patency. AB - Between January 1, 1979, and December 31, 1988, 149 infrapopliteal polytetrafluoroethylene (PTFE) bypasses were performed in 145 patients with chronic, critical, limb-threatening ischemia. These operations represented 27.9% of 534 infrapopliteal bypasses performed during the same period. There were 92 males and 53 females. Mean age was 71.8 +/- 12.3 years. Signs and symptoms of critical ischemia were gangrene, ulceration, and isolated rest pain in 101 (69%), 23 (15.3%), and 25 (16.7%) cases, respectively. A composite (PTFE-saphenous vein) graft was used in 53 (35%) cases. In 96 prosthetic bypasses the distal anastomosis was performed using vein patch angioplasty in 65 (44%) cases and directly in 31 (21%). The in-hospital mortality rate was 3.3%. Patency, limb salvage, and patient survival rates were plotted according to the actuarial method and the curves obtained were compared using the log-rank test. Actuarial survival rates were 68% +/- 5% and 57% +/- 7% at 3 and 5 years, respectively. Primary patency and lower limb salvage rates were 41% +/- 5% and 68% +/- 6% at 3 years and 35% +/- 9% and 65% +/- 10% at 5 years, respectively. There was no statistically significant difference noted in primary patency rates at 3 years according to the type of bypass (composite or all-prosthetic: 36% vs. 44%), the type of distal anastomosis (direct or vein patch angioplasty: 43% vs. 45%), the site of distal anastomosis (upper or lower half of the leg: 38% vs. 46%), lateral or medial placement of the bypass (39% vs. 43%), or according to whether or not it was a repeat operation (40% vs. 44%). In conclusion, patency rates using infrapopliteal PTFE bypasses are low. Certain technical approaches, although they do not seem to improve patency, definitely increase the feasibility of bypass and in our opinion decrease the risk of early failure in unfavorable anatomic settings. The limb salvage rates following infrapopliteal PTFE and composite bypass are encouraging and justify the use of routine distal revascularization, even in the absence of autogenous vein graft. PMID- 7786706 TI - Tumor embolism after pneumonectomy for primary pulmonary neoplasia. AB - We report a case of tumor embolism of the lower right extremity after right pneumonectomy. This is an infrequent complication and in most cases occurs during the intraoperative or immediate postoperative period. Our patient underwent surgery for primary pulmonary neoplasia (squamous cell carcinoma) and 4 hours later showed clinical signs of acute arterial occlusion in the lower right extremity. An emergency embolectomy was performed and a thrombus with tumor characteristics was extracted from the right common femoral artery. The pathologic features of this thrombus were identical to those of the pulmonary tumor. PMID- 7786707 TI - Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria. AB - Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention. PMID- 7786709 TI - Primary subclavian-axillary vein thrombosis. PMID- 7786708 TI - Transperitoneal medial visceral rotation. PMID- 7786711 TI - Meningococcal meningitis. PMID- 7786710 TI - Expanded programme on immunization. Progress towards poliomyelitis eradication, 1994. PMID- 7786712 TI - Yellow fever. Investigation of an epidemic in Imo State. PMID- 7786713 TI - Expanded programme on immunization. Measles elimination by the year 2000 in the Americas. PMID- 7786714 TI - Dracunculiasis. Global surveillance summary, 1994. PMID- 7786715 TI - Expanded programme on immunization. Diphtheria epidemic in the Newly Independent States of the former USSR, 1990-1994. PMID- 7786716 TI - Surveillance of measles following a national mass immunization campaign. PMID- 7786717 TI - Streptococcal infections. PMID- 7786718 TI - Ebola haemorrhagic fever. PMID- 7786719 TI - British Oncological Association and British Association of Surgical Oncology joint meeting. 9-11 July 1995. Abstracts. PMID- 7786720 TI - Compulsory HIV testing firmly rejected by official inquiry. PMID- 7786722 TI - Chiropody services: a feat for nursing? PMID- 7786723 TI - Long-term catheter use in the community. AB - This article discusses the advantages and disadvantages of long-term urinary catheters and explores patients' attitudes to catheterisation. The author argues that, with careful selection of equipment, long-term catheterisation can be acceptable to patients and a useful method of management for people whose lives are severely restricted by incontinence. PMID- 7786724 TI - Learning theories made easy: humanism. AB - This is the last of three articles explaining theories of learning with particular relevance to clinical areas. In the story so far, the Director of Nursing Education at the St Elsewhere Academy of Nursing is trying to create the ultimate programme of nursing education. In order to ensure that the very highest standards of teaching and learning are achieved, the DNE has decided to employ a theorist of learning. She first interviewed the candidate representing the school of behaviourism, and last week the cognitivist candidate made his presentation. The series now concludes with the humanist candidate--and the final decision. PMID- 7786721 TI - Bovine spongiform encephalopathy: something to beef about? PMID- 7786725 TI - Traumatic stress: a nurse therapist role? AB - The study of people who experience post-traumatic stress disorder (PTSD) is still in its infancy. Yet it is already clear that victims of more common traumatic events are as much at risk of suffering short- and long-term psychological consequences as the victims of major disasters. Nurse therapists and specialists clinics could have a key role in working with people experiencing PTSD and in educating others about the problems. PMID- 7786726 TI - Nurses' attire in a special hospital: perceptions of patients and staff. AB - Nurses' uniforms have been the subject of ongoing debate in many areas. Following the Ashworth Hospital inquiry, two wards at the hospital piloted the wearing of casual clothes by nurses. Patients and nurses in these wards completed questionnaires to evaluate the effects of the change. The results showed that the patients felt casual clothes helped remove a 'them and us' distinction and enhanced nurse/patient relationships. Nurses found casual clothes to be more comfortable and practical. Although concern was expressed that, without uniform, nurses might not be readily identifiable in an emergency situation, the change to casual clothing was generally viewed positively by both patients and nurses. PMID- 7786727 TI - Tissue viability. What causes pressure sores? PMID- 7786728 TI - Tissue viability. Home nursing equipment needs. PMID- 7786729 TI - All a misunderstanding. Interview by Dina Leifer. PMID- 7786730 TI - What the public says. PMID- 7786731 TI - One nurse's war. PMID- 7786733 TI - Child health: modules for the 90s. PMID- 7786734 TI - Using care plans to replace the handover. AB - This article describes the attempts of an NDU to make better use of written nursing care plans. It had been found that care plans were used more as historical records than as they were intended--to direct and plan care. The author outlines how staff identified the problem and then used primary nursing to enable the care plan to replace the oral handover. PMID- 7786732 TI - Mental health: a forum for support. PMID- 7786735 TI - Identifying the coping behaviours used by nurses in intensive care. AB - This study examines the use and perceived effectiveness among nurses of five coping styles: problem-focused coping, positive appraisal, help seeking, avoidance and aggression. Subjects were asked how they would cope with a conflict between themselves and a physician in the ward. The relationship between the coping behaviour and subjects' professional characteristics was explored. The subjects were 128 intensive cardiac care unit (ICCU) nurses. The results indicate that more experienced nurses use coping strategies less and may experience more burnout. The study also shows that nurses who participate in professional extra curricular activities tend to choose more effective coping strategies. PMID- 7786736 TI - Pain management: a review of the uses of epidural analgesia. AB - Epidural analgesia can be a valuable method of pain control in a variety of situations. It can facilitate early mobilisation and enhance recovery from surgery. This article describes the physiology of epidural pain relief and the nurse's role in monitoring patients effectively, recognising complications and minimising risk. PMID- 7786738 TI - One minute wisdom. Changes in nursing are not always good. PMID- 7786737 TI - Menorrhagia: care and treatment. AB - Approximately one tenth of women in this country experience menorrhagia. This can cause considerable discomfort, distress and curtailment of lifestyle. Hysterectomy is a common treatment, but morbidity and convalescence can be prolonged. Alternative surgical and pharmacological treatments are currently being developed which, it is hoped, will be available in the future. In the meantime, nurses have an important role to play in investigating, diagnosing and treating menorrhagia, and in supporting the women who experience it. PMID- 7786739 TI - Sister Susie. New horizons for pioneer New Nurse. PMID- 7786740 TI - Media: Messages from the frontline. PMID- 7786741 TI - Debate: a help or ... a hindrance. PMID- 7786743 TI - Positive action on equal opportunities. PMID- 7786742 TI - The really useful guide to portfolios and profiles (continuing education credit). AB - It is generally accepted that there is value in developing personal professional portfolios within nursing. This assumption is based on its inclusion as one of the main features of the UKCC's Standards for Education and Practice Following Registration (1): the requirement that all practitioners should maintain a personal professional profile. The fundamental purpose of the personal professional profiel is to 'provide a means for showing that nurses, midwives and health visitors have maintained and developed their professional knowledge and competence' (1). However, there is the potential to achieve much more than this rudimentary outcome. This Unit is relevant to UKCC Professional Development category Educational Development. PMID- 7786745 TI - Patient-controlled analgesia (continuing education credit). PMID- 7786746 TI - Consent to surgery: the role of the nurse. AB - In the first of two articles relating to consent issues, the author examines the role of the nurse in helping patients to have a more equal relationship with doctors when they sign a consent form. It is based on sociological research studies of consent to surgery (1-3). Next week, the author will look at issues relating to consent to research. PMID- 7786744 TI - Using benchmarking to improve practice. AB - Benchmarking is a relatively new addition to NHS quality initiatives. This article describes how a group of paediatric nurses set up a project to introduce benchmarking across units in the north west of England, and explores the benefits and disadvantages of this approach for nursing in general. PMID- 7786747 TI - NDUs: cut flowers. PMID- 7786748 TI - A day in the life.... PMID- 7786749 TI - Cardiology update. Thoracic aortic dissection. PMID- 7786750 TI - Cardiology update. Electrolytes in cardiac patients. PMID- 7786751 TI - Cardiology update. Central venous pressure. PMID- 7786752 TI - Cardiology update. Pulse oximetry. PMID- 7786753 TI - Concern over HIV testing. PMID- 7786760 TI - Viruria during acute Japanese encephalitis virus infection. AB - In this study, viruria following Japanese encephalitis virus (JEV) infection in mice has been shown to appear earlier in pregnant than in normal mice with proteinuria and haematuria. This was related to the production of splenic macrophage derived neutrophil chemotactic factor (MDF) following JEV infection. Intravenous inoculation of MDF in mice resulted in leakage of cells, proteins and erythrocytes in the urine as a result of altered capillary permeability. The isolation of virus from kidney did not correlate with the shedding of virus in the urine. The histological examination of sections of kidneys showed no morphological damage; however, ultrastructural degenerative changes in the mesangial cells were observed following JEV infection. These data suggest that JEV-induced macrophage derived factor regulates the leakage of proteins, erythrocytes and cells into the urine. PMID- 7786761 TI - Studies on early events of Borrelia burgdorferi-induced cytokine production in immunodeficient SCID mice by using a tissue chamber model for acute inflammation. AB - Lyme arthritis, one of the common features of Borrelia burgdorferi infection in the human, is associated with the production of various monocyte derived cytokines. To investigate the expression and regulation of cytokines during the acute phase of spirochete induced inflammation, a perforated Teflon chamber was implanted under the dorsal skin of severe combined immunodeficiency (SCID) and immunocompetent co-isogenic C.B-17 mice. The histology of the surrounding chamber tissue exhibited sterile inflammation with several features reminiscent of an inflamed synovium, i.e. infiltration of polymorphonuclear and mononuclear cells, fibroblast-like cells and neovascularization. The experimental inoculation of Borrelia burgdorferi into the chamber resulted in the production of TNF-alpha, IL 1 and IL-6 into the chamber exudate, in both the immunodeficient, disease susceptible SCID and the immunocompetent, disease resistant C.B-17 mice. Peak levels of TNF-alpha were reached at 2 hours and of IL-1 and IL-6 at 6 hours after infection; by 24 hours, cytokine levels were only marginal (IL-1, IL-6) or non detectable (TNF-alpha). Experimental infection by s.c. injection distant from the tissue chamber led to colonization of the spirochetes into the chamber, suggesting a tropism of the bacteria for this tissue. Thus, this model provides a system for studying acute events of Borellia burgdorferi induced cytokine regulation in a complex cellular, synovium-like environment that the bacterium encounters in vivo. PMID- 7786763 TI - Site of localization of Mycoplasma pulmonis and Mycoplasma hominis in the genital tract of female mice demonstrated by culture and scanning and immuno-electron microscopy. AB - Thirty young adult mice, of strain BALB/c, treated previously with progesterone, were inoculated intravaginally (10 mice) or directly into the uterus (10 mice) with Mycoplasma pulmonis and 10 mice remained uninoculated. Ten mice not treated with the hormone were also inoculated intrauterinely with M. pulmonis. The same numbers of mice treated with oestradiol were inoculated in the same ways with M. hominis. Vaginal swab specimens were obtained from all mice 7, 14 and 28 days after inoculation and samples of genital tract tissue were collected from pairs of mice at the same time intervals. Large numbers of M. pulmonis and M. hominis organisms were isolated from the vagina throughout the course of the experiments and they were cultured also from the cervix and uterine horns. Mycoplasma-like bodies were demonstrated by scanning electron microscopy in the cervix and in the uterus, but neither mycoplasmal species was found attached to vaginal epithelium. The results of silver-enhanced immunogold labelling in conjunction with scanning microscopy provided assurance that the mycoplasma-like bodies were, in fact, mycoplasmas. The importance of hormone treatment was indicated by the diminished susceptibility of untreated mice to M. pulmonis and the almost complete insusceptibility to M. hominis, shown by culture and scanning electron microscopy. PMID- 7786762 TI - Sexually differentiated response to choline in choline deficiency and ethionine intoxication. AB - A sex difference exists in the response of rats to a choline deficient diet and to ethionine intoxication. Female rats are less susceptible than males to the acute effects of choline deficiency, such as fatty liver and impaired secretion of triglycerides into blood plasma, while they are more susceptible to inhibition of liver protein synthesis and triglyceride accumulation by ethionine. These differences have been ascribed to sex differences in the biosynthesis of phosphatidylcholine in the liver of rats. The available data indicate that females are more dependent than males on the stepwise methylation of phosphatidylethanolamine rather than the direct incorporation of preformed choline. Continuous prefeeding with choline for three weeks was able to shift the female pattern of response to choline deficiency and ethionine intoxication towards that observed in males; thus, choline caused accumulation of hepatic triglycerides and a decrease in plasma triglycerides after choline deficiency, while it protected against ethionine induced triglyceride accumulation and protein synthesis inhibition in the liver. These results suggest that choline prefeeding in females makes them more dependent on choline availability and, thus, more susceptible to a choline deficient diet and less sensitive to ethionine intoxication, as are males. No effect of choline was observed in either choline deficient or ethionine intoxicated male rats. PMID- 7786764 TI - Pulmonary capillaries are smaller in the centre than in the periphery of the guinea-pig lung lobule: possible contributory mechanism for the centrilobular location of emphysema? AB - We used scanning electron microscopic morphometry of microvascular corrosion casts to compare the capillary structure in the centre and periphery of the lung lobule in the guinea-pig. Capillaries in the centre of the lobule had a lesser diameter than in the periphery (8.6 +/- 1.6 vs 10.4 +/- 1.9 microns respectively, P < 0.001). The polygonal capillary rings differed in structure between the centre and periphery of the lobule, although the number of branches remained constant. Capillary density in the centre of the lung (0.71 +/- 0.05) was significantly less than in its periphery (0.78 +/- 0.06, P < 0.001). We conclude that the capillary structure of the centre of the lung lobule is markedly different from that seen in the periphery. The smaller capillary diameter seen in the centre might be important in trapping polymorphonuclear leucocytes that lose the ability to deform after contact with cigarette smoke components; such an effect could explain why cigarette smoke induced emphysema tends to involve the centre of the lung lobule. PMID- 7786766 TI - Anti-glomerular basement membrane glomerulonephritis in the mouse: the role of macrophages. AB - An immunohistochemical study was undertaken on fixed, paraffin-embedded mouse kidney in order to elucidate the role and significance of infiltrating macrophages in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Tissue was available representing the full gamut of histological features seen in this model. The mouse macrophage-specific antigen F4/80 was detected in tissue sections of glomerulonephritic kidney and the pattern and extent of staining was compared with normal mouse kidney. In glomerulonephritic kidney, an increase in the number of F4/80-positive cells was evident in close proximity to and surrounding Bowman's capsule of those glomeruli which were severely damaged, with extensive fibrin deposition and well developed cellular crescents. F4/80-positive cells did not feature in the glomerular tuft or in the region of the parietal epithelium of Bowman's capsule even when extensive cellular crescents were present. Breaks in Bowman's capsule were not demonstrated. We conclude that F4/80-positive macrophages are not a major constitutive cell type of developing crescents in this mouse model of anti-GBM GN but, by virtue of their peri-glomerular localization, may be involved in the destructive process, perhaps producing signalling molecules which contribute to the inflammatory reaction. PMID- 7786765 TI - Mycobacterial granulomatous inflammation in the ulcerated caecum of indomethacin treated rats. AB - We report mycobacterial granulomatous inflammation in the ulcerated caecum of rats that received indomethacin. Two groups of male rats were treated with dietary indomethacin 3 mg/kg/day or untreated diet for 3 weeks. Six out of 8 indomethacin treated rats showed both ulceration and inflammation of the caecal mucosa. Two of the rats showing caecal ulceration also showed distinct granulomatous inflammation of the caecal mucosa and acid-fast bacilli were identified within granulomata. None of the other indomethacin treated or control rats contained acid-fast bacilli within caecal tissue sections but they were present, in the same sections, within the lumen of most rats in both groups. Polymerase chain reaction analysis identified the mycobacterial 65 kDa GroEL gene within control and granulomatous caecal tissue. In a repeat of indomethacin administration to a third group of rats, culture of both non-granulomatous caecal tissue (containing histologically identified luminal acid-fast bacilli) and faecal samples for mycobacteria was negative. PMID- 7786767 TI - Increased Na+,K(+)-pump activity in erythrocytes of rabbits fed cholesterol. AB - Na+,L(+)-pump activity, intracellular sodium, potassium and magnesium concentrations and membrane cholesterol content were studied in erythrocytes of rabbits fed cholesterol. The average activity of the Na+,K(+)-pump in erythrocytes of rabbits with high plasma cholesterol was twice that in erythrocytes of control animals. Analysis showed a positive correlation between the pump activity and plasma cholesterol. The sodium content in erythrocytes correlated negatively with plasma cholesterol, as well as with the Na+,K(+)-pump activity. No significant differences in potassium and magnesium concentrations or in the membrane cholesterol content were observed between the two groups. The results indicate that modulation of the pump activity by cholesterol is not necessarily mediated by changes in the membrane viscosity. PMID- 7786769 TI - Low molecular weight heparin(s). PMID- 7786768 TI - Differential decline of rabbit chondrocytic dehydrogenases with age. AB - We have previously found that the restoration of cartilage matrical proteoglycans is preceded by markedly increased activity of uridine diphosphoglucose dehydrogenase (UDPGD), an enzyme directly associated with glycosaminoglycan (GAG) synthesis, and by increased activity of enzymes of the major energy yielding pathways (glucose-6-phosphate dehydrogenase (G6PD), glyceraldehyde-3-phosphate dehydrogenase (GAPD) and succinate dehydrogenase (SDH)). We did not find an increase in lactate dehydrogenase (LDH). In the present longitudinal study of rabbits (from 5 weeks to 42 months of age), we looked for age related changes in the activity of these enzymes in auricular chondrocytes, as well as for collagen and GAG content. Collagen content (micrograms/wet weight) increased up to 12 months and remained stable; total GAG content (micrograms/wet weight) reached its maximal value at growth and then declined gradually, reducing the GAG/collagen ratio dramatically from 36 to 8. At any age LDH was two to three times more active than either G6PD, aldolase, or GAPD. SDH and UDPGD activities were even lower. The age related changes varied: (1) LDH and GAPD were stable and did not change with either growing or aging; (2) G6PD and aldolase reached their maximal activity at 3-9 months, followed by a sharp drop at 12 months. G6PD remained stable, while aldolase continued to decline, although more slowly; (3) Maximal activity of SDH and UDPGD was measured at 5 weeks. Thus, the changes in enzyme activity in chondrocytes with age were specific for each enzyme. The significant decline in G6PD, aldolase, the rate-limiting enzymes of the pentose shunt and classic glycolysis, and SDH markedly reduced the ability of chondrocytes to generate energy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786770 TI - Clinical significance of serum thymidine kinase in adult T-cell leukaemia and acute myeloid leukaemia. AB - To clarify the clinical and biological significance of serum thymidine kinase (TK) in adult T-cell leukaemia (ATL) associated with human lymphotropic virus type-I (HTLV-I) and in acute myeloid leukaemia (AML), TK was measured in 52 patients with ATL (acute ATL, 35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smouldering ATL, three patients), and in 27 patients with AML (one FAB MO, one M1, 10 M2, seven M3, five M4, one M5, one M6, one MU). In ATL patients, statistical analysis disclosed a close correlation between TK level and the leucocyte count (P < 0.01), and absolute number of abnormal lymphocytes (P < 0.01). However, no correlation was observed between serum lactic dehydrogenase (LDH) level and these items. Concerning the therapeutic response, a statistical difference was present in TK between complete remission and no response (P < 0.05), but not in LDH. We also investigated a significant inverse correlation between TK level as well as LDH level and the length of survival after the initial diagnosis (P < 0.01). In AML patients a close correlation of TK level with the count of leucocytes (P < 0.01), percentage of blasts in the blood (P < 0.05), therapeutic response (P < 0.01) and the length of survival after the initial diagnosis (P < 0.05) was present. Therefore the TK level may indicate the aggressiveness of leukaemic cells and predict the response to the chemotherapy and the length of survival in ATL and AML. PMID- 7786771 TI - Prognostic implications of DNA aneuploidy in 156 untreated multiple myeloma patients. Castelano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. AB - In this study the incidence of DNA aneuploidy in a large series of untreated multiple myeloma (MM) patients was assessed in order to determine its clinical and prognostic significance. A total of 156 MM patients were included in the study. DNA measurements were performed in all cases at diagnosis using two different flow cytometry methods: (1) propidium iodide (PI) staining on isolated nuclei, and (2) CD38/PI double staining on whole cells. The DNA ploidy status was correlated with the most relevant clinical and haematological disease characteristics. From the 156 cases analysed, 91 (58%) were aneuploid (56% hyperdiploid and 2% hypodiploid). The correlation between the two techniques on the detection of DNA aneuploidy was excellent, although CD38/PI double staining would be preferable in cases with < 5% of DNA aneuploid plasma cells (PC). Upon comparing the clinical and haematological disease characteristics of hyperdiploid versus diploid cases, the former group was characterized by a lower age, reduced incidence of anaemia, lower beta 2M levels, higher proliferative activity within the residual normal haemopoietic cells, increased expression of CD56 antigen in PC, and higher proportion of PB CD4+ T cells. In contrast, diploid cases had a higher expression of the CD10, CD20 and CD15 antigens and greater numbers of PB CD56+CD3- NK cells (P < 0.05). Circulating PC were identified in six cases, all being diploid. Overall survival was significantly longer in hyperdiploid compared to diploid MM (P = 0.02). These results show that over 50% of MM patients are aneuploid, almost all of them being hyperdiploid. This characteristic is associated with better prognosis. PMID- 7786772 TI - Idiotypic oligonucleotide probes to detect myeloma cells by mRNA in situ hybridization. AB - An mRNA in situ hybridization (ISH) method which used non-radioactive idiotypic oligonucleotide probes has been used to detect malignant cells in the bone marrow and peripheral blood of patients with multiple myeloma. For each of two patients with multiple myeloma a pair of biotinylated antisense oligonucleotide probes (18 22mer) was prepared from non-germline sequences of the rear-ranged immunoglobulin heavy chain (IgH) gene. These oligonucleotide sequences were not homologous with any previously published sequence. The probes from each patient were specific as shown by a failure to hybridize to any cells from six other myeloma patients and four normal individuals. Specific staining of IgH gene mRNA occurred only when the myeloma cells and the sequence of the probe used were from the same patient. Using simultaneous fluorescent immunocytochemistry it was shown that more than 95% of the ISH-positive cells expressed the malignant light chain in their cytoplasm. ISH positive cells were found in 1-4% of the peripheral blood mononuclear fraction of these two patients. These studies show that idiotypic oligonucleotide IgH gene probes can be used to identify individual cells belonging to the malignant clone and offer the possibility of developing innovative tumour-specific therapeutic procedures using antisense technology for patients with myeloma. PMID- 7786773 TI - Der(16)t(1;16)(q11;q11) in myelodysplastic syndromes: a new non-random abnormality characterized by cytogenic and fluorescence in situ hybridization studies. AB - The der(16)t(1;16)(q11;q11) is a frequent recurrent rearrangement in solid tumours such as breast carcinomas and Ewings sarcomas. Recently, this abnormality was described also in multiple myeloma. We identified a der(16)t(1;16)(q11;q11) in three patients with myelodysplastic syndrome, either during preleukaemic phase (n = 2) or at the time of blastic transformation (n = 1). Breakpoints were ascertained by fluorescence in situ hybridization (FISH) using specific centromeric alpha-satellite probes and whole chromosome painting for chromosome 1 and chromosome 16. These observations, combined with isolated cases of the literature, suggest that der(16)t(1;16)(q11; q11) is a nonrandom abnormality associated with myelodysplastic syndromes. PMID- 7786774 TI - Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia. AB - The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML. PMID- 7786775 TI - Clonal analysis of haemopoietic cells in essential thrombocythaemia. AB - Essential thrombocythaemia (ET) is a myeloproliferative disease (MPD) predominantly involving the platelet lineage, with a diagnosis often difficult to establish in practice. The demonstration of a clonal haemopoiesis can contribute to diagnosis. The clonal origin of blood cells can be assessed in female patients using X-chromosome-linked polymorphisms, assuming a random inactivation of the X chromosome. The human androgen receptor gene HUMARA has been used for this purpose, taking advantage of a highly polymorphic trinucleotide repeat in the first exon. The close proximity of the polymorphic trinucleotide repeat to four methylation sites permits a clonal analysis based on the polymerase chain reaction. We have used this technique to study the clonality of haemopoietic cells in 32 patients with ET and 23 age-matched control heterozygotes for the HUMARA polymorphism. A monoclonal pattern of haemopoiesis was detected in unfractionated nucleated blood cells from 22 patients, suggesting that haemopoiesis is essentially monoclonal in a majority of cases in this disease. In some patients a monoclonality of granulocytes was documented, whereas the mononuclear fraction had a polyclonal pattern of X-inactivation. Finally, in two patients for whom a polyclonality had been found in unfractionated blood, analysis of G6PD transcripts in platelets revealed a clonal megakaryocytopoiesis. These findings confirm the heterogeneity of haematological abnormalities in ET patients and the potential utility of a multifaceted laboratory approach to investigate these patients. PMID- 7786777 TI - Hemizygous expression of the wild-type p53 allele may confer a selective growth advantage before complete inactivation of the p53 gene in the progression of chronic myelogenous leukaemia. AB - We analysed the expression of the p53 gene in various clinical phases of chronic myelogenous leukaemia (CML) by quantitative reverse transcriptase (RT) polymerase chain reaction (PCR). Hemizygous expression of the wild-type p53 allele was observed in two samples showing the loss of one p53 allele, and affected p53 expression was associated with p53 allelic loss rather than the clinical phase of CML. In four patients with CML showing p53 inactivation, we performed a detailed sequential analysis of p53 allelic loss, p53 mutation and expression from the onset of the disease to the patients' death. Consequently, we demonstrated that the loss of a wild-type p53 allele preceded mutation of the remaining allele, and that cells hemizygous for the wild-type p53 allele dominated those with both wild type alleles, then were replaced by cells with complete p53 inactivation. These observations indicate that not only complete p53 inactivation but also hemizygous expression of the wild-type p53 allele may confer a selective growth advantage, and that the former is implicated in a more malignant phase than the latter. Alternatively, the inactivation of another undefined anti-oncogene on chromosome 17p may allow selective growth before the p53 mutation occurs. PMID- 7786776 TI - Characterization of genomic BCR-ABL breakpoints in chronic myeloid leukaemia by PCR. AB - In order to understand better the mechanism of translocation between the BCR and ABL genes in CML, we have exploited a 'bubble PCR' technique to clone genomic breakpoints. BCR-ABL junction fragments were successfully amplified and sequenced in 14/32 (43%) patients tested. Breakpoints were dispersed throughout the major breakpoint cluster region without any clustering or hot spots. In three cases Alu sequences were found at or near the breakpoint on the ABL side of the translocation but no other obvious sequence homologies were found either in BCR or ABL. The translocation event was characterized further in three other patients by amplifying the reciprocal ABL-BCR junction on the 9q+ chromosome and also normal ABL around breakpoints. In two of these patients a few nucleotides of BCR and ABL were either duplicated or deleted on translocation, suggesting that staggered cuts had been made in the DNA strand prior to recombination. In the third patient 50 bp of ABL was deleted and 159 bp of M-BCR including exon b3 was duplicated, indicating either that the single-stranded cuts may span a larger distance than previously thought or that another mechanism, perhaps involving gene conversion, may be involved in this instance. PMID- 7786780 TI - Analysis of heat-shock protein expression in myeloid leukaemia cells by flow cytometry. AB - Expression of heat-shock proteins (hsp) was analysed in the leukaemic cells of 12 patients with acute myeloid leukaemia (AML) and nine patients with chronic myeloid leukaemia (CML). Using monoclonal antibodies to hsp70, hsp90 and hsp60 (ML30, a mycobacterial antigen with homology to human hsp60), we measured hsp levels by flow cytometry of permeabilized cells. Mononuclear cells from 10 healthy volunteers were also examined. The results demonstrate that hsp expression is significantly increased (P < 0.01) in the circulating cells of patients with AML compared with cells from CML patients, and compared with normal peripheral blood mononuclear cells. This increased pattern of expression was found for all three heat-shock protein families included in this study. Mononuclear cells from leukaemic patients showed a heterogenous pattern of hsp expression, between different patients, between cells from individual patients, and between the different hsp proteins examined. It is possible that hsp expression relates to the differentiation state or proliferative potential of these leukaemic cells. PMID- 7786779 TI - Evidence for a paracrine pathway of B-cell stimulation in hairy cell leukaemia. AB - It is a well-known phenomenon that the growth of malignant B-lymphocytes, i.e. hairy cells, is regulated by cytokines. Several investigators have suggested that the stimulating cytokines are produced by the malignant B cells themselves, indicating an autocrine growth regulation. In this paper we demonstrate that T lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth-stimulating T-cell clones derived from peripheral blood is identical in patients with hairy cell leukaemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alpha (IFN alpha), but not antibodies against tumour necrosis factor alpha (TNF alpha) or interleukin-2 (IL-2), completely inhibit the growth stimulating activity. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells. PMID- 7786781 TI - Attenuated-dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results. AB - AML in the elderly is characterized by intrinsic biological features implying an enhanced chemoresistance. Intensive chemotherapy should be the treatment of choice, but the standard doses could induce unacceptable rates of aplastic deaths. We evaluated the efficacy of an induction protocol with attenuated-dose idarubicin (IDA) 8 mg/m2 for 3 d plus cytarabine and etoposide in 26 AML patients aged > 60. 18 patients (69%) achieved CR, five (19%) were non-responders and three (12%) died during induction. To compare the pharmacokinetics of IDA between elderly and young patients, we assayed daily the serum level of the drug and of its metabolite (idarubicinol, IDAol) in a group of eight elderly patients who received a dose of 8 mg/m2 (group A) and in a group of nine younger AML patients treated with 12 mg/m2 (group B). The apparent terminal half-life of IDAol was significantly longer in the elderly than in the younger patients (mean half-life 59.7 h versus 41.4 h, P < 0.05). The values of the area under the serum concentration curve of IDAol indicated that the two patient groups received a very similar exposure to the drug despite the different doses. In conclusion, this protocol, based on attenuated doses of IDA, compares well with the results obtained previously in similar age-matched patient series. PMID- 7786778 TI - Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-gamma and tumour necrosis factor-alpha in patients with myelodysplastic syndromes. AB - The effects of interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL 12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL 12 and/or IL-2 (type C response). All patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3- CD56+ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-gamma and TNF-alpha production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL 12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients. PMID- 7786782 TI - Evidence for a light chain restriction of glycoprotein Ib/IX and IIb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP). AB - To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPIIb/IIIa-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IIIa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes. PMID- 7786783 TI - A low M(r) GTP-binding protein, Rap1, in human platelets: localization, translocation and phosphorylation by cyclic AMP-dependent protein kinase. AB - Subcellular fractions were prepared from human platelet membranes by sucrose density gradient centrifugation and the localization of a low M(r) GTP-binding protein, rap1 protein (Rap1) was analysed by immunoblotting using a specific antibody. Rap1, which has been purified from human platelets, was found to be located in plasma membrane and alpha-granule fractions in resting platelets. Treatment of isolated alpha-granules with pronase led to proteolysis of Rap1, indicating that this protein is exposed to the cytoplasmic face of the granules. Degranulation of alpha-granules consists of translocation and subsequent fusion of the granules with the open canalicular system. Activation of this process by thrombin induced the redistribution of Rap1 on the alpha-granules to plasma membranes. On the other hand, Rap1 is known to be phosphorylated by cyclic AMP dependent protein kinase (A-kinase) in vitro and in vivo. In intact human platelets, phosphorylation of Rap1 by A-kinase in response to prostaglandin E1 (PGE1) was observed only in Rap1 localized in plasma membranes and not on alpha granules, although Rap1 was phosphorylated in a cell-free system when plasma membranes and alpha-granule membranes were exposed to A-kinase as substrates. These results strongly suggest that Rap1 in plasma membranes and the protein on alpha-granules are regulated by different mechanisms, and have different functions. PMID- 7786784 TI - Fibrin degradation product (FnDP) assays: analysis of standardization issues and target antigens in plasma. AB - The in vivo formation of fibrin and its subsequent secondary fibrinolytic digestion yields a variety of crosslinked fibrin degradation products (XL/FnDP). One of these is known as D-dimer and a variety of ELISA-type commercial kits using monoclonal antibodies to D-dimer have been developed. We have investigated the possibility of establishing a standard such that these various kits might indicate the same levels of D-dimer in the same samples. We have concluded that because it seems that each individual monoclonal antibody to D-dimer targets a unique and distinct epitope in the FnDP fraction the notion of introducing a standard D-dimer which will respond uniformly to each D-dimer monoclonal antibody is not feasible. Using various monoclonal and polyclonal antibodies in conjunction with gel exclusion chromatography we have examined human plasma derived from patients with disseminated intravascular coagulation (DIC) which contained high levels of fibrin degradation products (FnDP). The data suggested that the FnDP fraction in plasma contained mostly high molecular weight (> 2 x 10(6) daltons) crosslinked fragments which contain high levels of fibrinopeptide A. Many of these crosslinked fragments crossreact with antibodies to D-dimer because they each contain D-dimer as a structural component. On the basis of this data, a novel sequence of events is proposed which may occur during the aggregation of fibrin in vivo. PMID- 7786785 TI - Resistance to activated protein C activity of an anti-beta 2-glycoprotein I antibody in the presence of beta 2-glycoprotein I. AB - Some researchers claim that lupus anticoagulant-positive plasma may cause a false positive reaction in the test for activated protein C (APC) resistance, a hereditary thrombophilic state characterized by abnormal factor V, which frequently causes venous thrombosis. We investigated whether anti-beta 2 glycoprotein I antibody (aGPI), which has recently come to be regarded as an anti cardiolipin antibody (aCL) itself, might have an effect on the APC resistance test. PMID- 7786786 TI - Acquired hypochromic and microcytic sideroblastic anaemia responsive to pyridoxine with low value of free erythrocyte protoporphyrin: a possible subgroup of idiopathic acquired sideroblastic anaemia (IASA). AB - Patients with idiopathic acquired sideroblastic anaemia (IASA) usually show macrocytic or normocytic anaemia and increased free erythrocyte protoporphyrin (FEP). The mean cell haemoglobin concentration is normal or slightly low. Here we report a pyridoxine-responsive IASA patient with microcytic and hypochromic anaemia and low FEL level; these features are usually seen in cases of hereditary sideroblastic anaemia. Microcytosis increased during therapy. There may be a subgroup of IASA with microcytic and hypochromic anaemia, low normal FEP and some response to pyridoxine like hereditary sideroblastic anaemia. PMID- 7786787 TI - Random X chromosome inactivation in a female with a variant of Wiskott-Aldrich syndrome. AB - A 15-month-old female presented with eczema, thrombocytopenia, recurrent infections and failure to thrive. She had low serum IgM and IgG subclasses and an abnormal lymphocyte proliferative response to periodate in vitro. Molecular X chromosome inactivation analysis, using the polymorphic HUMARA DNA probe, showed that the infant has random X chromosome inactivation. We conclude that she has an atypical form of Wiskott-Aldrich syndrome which may be inherited in an autosomal recessive manner. PMID- 7786788 TI - Successful bone marrow transplantation for idiopathic hypereosinophilic syndrome. AB - A 21-year-old man who had an increased number of eosinophils with morphological abnormalities, bone marrow fibrosis and multiple organ dysfunction failed to respond to methylprednisolone and hydroxyurea. He was diagnosed with hypereosinophilic syndrome (HES) probably due to myeloproliferative disorder, and underwent allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical sibling. The engraftment was confirmed on day 21 after BMT, but the patient developed acute graft-versus-host disease (GVHD) with grade I veno-occlusive disease, and transient increase of eosinophils of the donor type followed by chronic GVHD of the extensive type. These complications were eventually controlled with cyclosporin A. The patient survived free of disease for more than a year after BMT. Allo-BMT seems to be a possible treatment of HES/MPD. PMID- 7786789 TI - Refractory cytopenia with t(1;7),+8 abnormality and dysplastic eosinophils showing intranuclear Charcot-Leyden crystals: a fluorescence in situ hybridization study. AB - A case of refractory cytopenia and marrow eosinophilia showing t(1;7) translocation and concomitant trisomy 8 is reported. The eosinophils were dysplastic, and showed the unique feature of intranuclear Charcot-Leyden crystal formation, giving rise to a 'lip-like' appearance. We speculate that this unusual cytologic feature resulted from abnormal precipitation of Charcot-Leyden crystal protein in the eosinophils. By fluorescence in situ hybridization using a chromosome 8 specific alpha-satellite probe, the abnormal eosinophils were shown to have derived from the abnormal clone. We postulate that the dysplastic clone might have retained a differentiation potential and be responsive to normal haemopoietic stimuli. PMID- 7786790 TI - Expression of an erythropoietin-like gene in the trout. AB - Cross-species Northern blot hybridization and radioimmunoassay have provided evidence for the expression of an erythropoietin (EPO)-like gene in the rainbow trout. The principal site of EPO-like mRNA and antigen expression in the adult trout appears to be the kidney which also acts as the major erythropoietic organ. The data suggest that a locally produced EPO-like factor may regulate renal erythropoiesis in bony fish and, furthermore, they identify a possible evolutionary origin for renal EPO production in mammals. PMID- 7786791 TI - Scintigraphic evaluation of the haemopoietic bone marrow using a 99mTc-anti granulocyte antibody: a validation study with 52Fe. AB - To specify the validity of bone marrow scanning using a monoclonal anti granulocyte antibody labelled with 99mTc (BW 250/183) for the functional assessment of haemopoiesis, we compared this method with 52Fe scan in 16 patients with haematological disorders. The examinations were performed using a rectilinear whole-body scanner and the distribution of the two tracers was assessed visually and quantitatively in anatomical bone marrow segments, the spleen and liver. Qualitative comparison showed concordance in the bone marrow distribution of the two tracers in 83% of the segments. Discrepancies were found in six patients with hypoplastic or aplastic marrow. The spleen was visualized in all cases with the 99mTc-Moab, including nine patients without splenic haemopoiesis (i.e. without spleen uptake of 52Fe). The uptake of the two tracers, quantified in bone marrow segments and the spleen, correlated well (P < 0.001), but not in the liver (NS). The correlation between the uptake values for each patient was excellent, except in cases of aplastic bone marrow. In conclusion, bone marrow scanning using a 99mTc labelled anti-granulocyte monoclonal antibody enables functional evaluation of the distribution of haemopoiesis. Limitations include the evaluation of bone marrow aplasia and identification of splenic haemopoiesis, for which 52Fe remains the tracer of choice. PMID- 7786792 TI - The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event. AB - We have recently identified a common ALL patient which harboured a chromosomal fusion between the TEL gene on chromosome 12 and the ABL gene on chromosome 9. We designed an RT-PCR assay to screen 186 adult ALL and 30 childhood ALL patients for this novel translocation. We were unable to identify any additional cases with a TEL/ABL fusion product. PMID- 7786793 TI - Detection of the BCR-ABL gene by reverse transcription/polymerase chain reaction and fluorescence in situ hybridization in a patient with Philadelphia chromosome negative acute lymphoblastic leukaemia. AB - The Philadelphia (Ph) chromosome is detected in leukaemia cells in approximately 20% of adults with acute lymphoblastic leukaemia (ALL). When treated with chemotherapy alone, Ph-positive ALL has a poor prognosis, and patients may benefit from bone marrow transplantation in first remission. Here we report a patient with chromosomally normal bone marrow, in all 60 cells analysed, who was found to have the p210-type BCR-ABL chimaeric transcript by RT/PCR. Fluorescence in situ hybridization was labelled cosmid probes for BCR and ABL showed the presence of BCR-ABL juxtaposition on a normal chromosome 22 in leukaemia cell metaphases. We conclude that molecular and cytogenetic methods should be used in conjunction to detect the BCR-ABL gene rearrangement in ALL. PMID- 7786794 TI - Haemoglobin Dhofar is linked to the codon 29 C-->T (IVS-1 nt-3) splice mutation which causes beta+ thalassaemia. AB - Investigations of a young man with apparent thalassaemia minor showed that he was a heterozygote for a rare abnormal haemoglobin variant, Hb Dhofar. The amino acid replacement is in the beta-globin chain (beta 58 Pro-->Arg) and is therefore not consistent with the observed proportion of Hb Dhofar, as in both this and the original case, it constituted only 15% of the total haemoglobin. We have determined the basis of the low expression of this mutant, which is due to its linkage to a thalassaemic splicing mutation on the same beta-globin gene at codon 29 (C-->T). The finding of this thalassaemia mutation linked to Hb Dhofar not only explains the low level of Hb Dhofar, but also provides evidence that the codon 29 C-->T, IVS-1 splice junction mutation causes a beta+ form of thalassaemia. PMID- 7786796 TI - Enhanced Mg(2+)-ATPase activity in ghosts from HS erythrocytes and in normal ghosts stripped of membrane skeletal proteins may reflect enhanced aminophospholipid translocase activity. AB - Hereditary spherocytosis (HS) is a congenital haemolytic anaemia which is characterized by a great variety of structural defects in the red cell's membrane skeleton and/or deficiencies in particular membrane (skeletal) proteins. Enhanced (Mg2+)-dependent adenosine triphosphatase (Mg(2+)-ATPase) activities, varying from 115% to 160%, were invariably found in erythrocyte ghosts derived from 13 HS patients. Similarly, an enhancement of Mg(2+)-ATPase activity by 30% is observed in normal red cell ghosts that have been stripped of the greater part of their membrane skeletal proteins by treatment with a low ionic strength buffer. Reassociation of those stripped ghosts with spectrin reduces the enhanced Mg(2+) ATPase activity to its original level. Since in both cases, HS ghosts and stripped normal ghosts, the stabilizing effects that the membrane skeleton exerts on the maintenance of an endofacial localization of the aminophospholipids are impaired, the enhanced Mg(2+)-ATPase activity is interpreted to reflect an increased activity of the aminophospholipid translocase. The present observations therefore support a role of the membrane skeleton in the stabilization of phospholipid asymmetry in the red cell membrane and consequently in reducing the energy consumption of the translocase. PMID- 7786795 TI - Clonal and non-clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis. AB - We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein-Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV-associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease. Although HLH did not show histological and/or haematological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation. PMID- 7786797 TI - Low plasma heparin cofactor II levels in thalassaemia syndromes are corrected by chronic blood transfusion. AB - Low plasma heparin cofactor II (HCII) levels are associated with a thrombotic tendency, and we have previously shown these to be decreased in a variety of haemolytic conditions. The risk of thrombosis is recognized to be increased in both thalassaemia major (TM) and intermedia (TI), although the exact mechanisms are poorly understood. HCII levels have therefore been compared in 20 untransfused patients with TI and 20 regularly transfused TM patients to determine the influence of transfusion on HCII. Additionally, untransfused TI patients have been commenced on regular red cell transfusion and the effects on correction of low HCII levels investigated. HCII levels were significantly lower in the untransfused TI patients (mean 0.56 +/- 0.06 U/ml) compared to TM patients (mean 0.85 +/- 0.1 U/ml; P < 0.001). Levels in TI were significantly less than in healthy age-matched controls (P < 0.001) and correlated with Hb values (r = 0.8), whereas levels in TM were at the lower end of the normal range. ATIII values were within the normal reference range in both TI and TM, and HCII antigen showed a parallel reduction to HCII activity, indicating that reduction in HCII is not a consequence of increased thrombin consumption. Three patients with TI were commenced prospectively on hypertransfusion programmes which resulted in a slow normalization of their levels taking 2-3 months. These findings support a hypothesis that the low HCII levels are related to increased red cell turnover and can be normalized once this turnover has been suppressed by hypertransfusion. The thrombotic risk to patients with low HCII levels in the presence of haemolysis might in principle be decreased by such transfusion regimes. PMID- 7786798 TI - Haemoglobin Tunis-Bizerte: a new alpha 1 globin 129 Leu-->Pro unstable variant with thalassaemic phenotype. AB - A Leu-->Pro substitution at position 129 of the alpha 1 globin gene was detected in three members of a Tunisian family by sequencing the whole alpha 2 and alpha 1 DNA. The mutation was verified by dot-blot allele-specific hybridization as well as by digestion of PCR and RT-PCR products with Nci I, since the alpha 1(129) T- >C mutation creates an additional recognition site for the above-mentioned enzyme. The alpha 1(129)(H12)Leu-->Pro substitution disturbs helix H resulting in alpha-thal trait most probably because the unstable alpha-globin chain variant cannot form alpha beta dimers. A search for the abnormal Hb and for the abnormal alpha globin chain by isoelectric focusing, carboxymethyl cellulose chromatography and electrospray ionization mass spectrometry was negative. In the heterozygous state, the alpha 1(129)(H12) Leu-->Pro variant is manifested by microcytosis (MCV approximately 73 fl), whereas in the homozygous state there is moderate anaemia with marked microcytosis (Hb 11.6 g/dl, MCV 65 fl). PMID- 7786799 TI - Leukaemic non-Hodgkin's lymphomas with hyperdiploid cells and t(11;14)(q13;q32): a subtype of mantle cell lymphoma? AB - The present study describes five patients with leukaemic non-Hodgkin's lymphoma (NHL) detected on the basis of particular morphology and cytogenetic findings. With respect to histological, immunological and cytogenetic features these NHL are closely related to mantle cell lymphoma/intermediate differentiated lymphocytic lymphoma. However, the presence of unusual large cells associated with the t(11;14)(q13;q32) translocation and numerical chromosome changes, in the near triploid or near tetraploid range, could delineate a particular subtype of mantle cell lymphoma. PMID- 7786800 TI - Modulation of cell kinetics and cell cycle status by treating CD34+ chronic myeloid leukaemia cells with p53 antisense phosphorothioate oligonucleotides. AB - Mutations of the p53 tumour suppressor gene occur in 20% of chronic myeloid leukaemia (CML) patients in blastic crisis, but it is still uncertain whether this inactivation plays a role in the pathogenesis of blastic transformation or in maintaining the leukaemic proliferation in CML, as it does in several solid tumours. We have previously shown that more than 50% of both normal and CML CD34+ cells express the p53 protein. However, haemopoietic cells at different phases of the cell cycle express p53 with different conformations, suggesting that the function of p53 may be closely regulated during the cell cycle. In order to elucidate the mechanism by which p53 suppresses cell proliferation, we evaluated the effects of inhibiting p53 expression on cell cycle and cell kinetics of chronic phase CML (n = 12) and normal (n = 7) bone marrow light-density cells and purified CD34+ progenitors by using an 18-mer modified antisense oligonucleotide which targets the region covering the six base pairs immediately before the first codon and the first four coding codons of p53. We found that the number of cells positive for the cell cycle-specific nuclear antigen Ki67 and for the BrdU monoclonal antibody (McAb) was significantly increased after p53 antisense olignucleotide treatment. At the same time, p53 protein expression was completely abrogated in both light-density and CD34+ cells. In addition, DNA analysis by flow cytometry demonstrated that the number of cells in quiescent phases of the cell cycle (G0-G1) was significantly decreased after exposure of light-density cells to p53 antisense oligomers, whereas the number of cells in S or G2-M phases was increased. Furthermore, the longer the incubation time the higher the increase in cell proliferation. Treatment of CML, cells with p53 antisense oligomers also resulted in significantly increased numbers of CFU-GM colonies. Our data suggest that p53 is a negative regulator of cell proliferation and its action is mediated through changes in cell cycle kinetics, mainly before the S phase. We can further speculate that the loss of p53 function, at the time of blastic crisis of CML, may play a role, in combination with other genetic changes (p210 BCR/ABL, Rb gene abnormality, others to be defined), in inducing disturbances in cell proliferation, differentiation, and apoptosis. PMID- 7786801 TI - Assessment of clonal evolution at Ig/TCR loci in acute lymphoblastic leukaemia by single-strand conformation polymorphism studies and highly resolutive PCR derived methods: implication for a general strategy of minimal residual disease detection. AB - Junctional sequences of immunoglobulin (Ig)/T-cell receptor (TCR) gene rearrangements are used as patient-specific PCR targets for the detection of minimal residual disease (MRD) in acute lymphoblastic leukaemias (ALLs). Clonal evolution of gene rearrangements is a major pitfall of this strategy. Using high resolution PCR-based analyses (including denaturing gel electrophoresis and single-stranded conformation polymorphism (SSCP)) we have compared Ig/TCR gene rearrangements at presentation and relapse in a series of ALLs. These methods allow an unambigous comparison of rearrangements taking into account junctional size and nucleotide sequence information and allow a precise assessment of the clonal evolution. V gamma-J gamma and V delta 1-J delta 1 rearrangements were analysed in 12 T-ALLs. VH-JH, V gamma-J gamma, V delta 2-D delta 3 and, in selected cases, DH-JH rearrangements were studied in 14 B-lineage ALLs. Clonal evolution, regarding major rearrangements, occurs for at least one of these loci in 2/12 T-ALLs and in 5/14 B-lineage ALLs. Clonal evolution is more marked for minor rearrangements than for major ones. As shown using SSCP analysis, rearrangements observed at relapse are sometimes found in minor clones at presentation which are therefore selected in vivo by a proliferative advantage. These data, as well as those from the available literature, suggest the use of at least two patient-specific probes to detect MRD in ALLs. A general strategy including selected Ig/TCR rearrangements and chromosomal abnormalities as PCR targets is proposed. PMID- 7786802 TI - Over-expression and amplification of the CDC2 gene in leukaemia cells. AB - The expression and structure of the cdc2 gene, one of the master regulators of the eukaryotic cell cycle, were investigated in fresh leukaemic cells from 51 cases of various types of leukaemia. Cdc2 mRNA transcripts were detectable in approximately 40% (21/51) of cases by Northern blotting. Over-expression of cdc2 mRNA as compared to normal bone marrow cells was noted in 10/21 cases with detectable cdc2 mRNA transcripts. Amplification of the cdc2 gene was found in three cases. Cdc2 mRNA was over-expressed in these three cases, suggesting that gene amplification is a direct cause of mRNA over-expression in a subset of cases. Cell proliferative capacity was well correlated with the amount of cdc2 mRNA transcripts, i.e. 3H-thymidine incorporation was highest in cases with cdc2 mRNA over-expression and was significantly higher in cdc2-positive cases than in cdc2-negative cases. These results suggest that over-expression of CDC2, which is due to the gene amplification in some cases, might play a role in altered growth of leukaemic cells. PMID- 7786803 TI - Predicting outcome in the tethered cord syndrome: a study of cord motion. AB - Thirty-two children with spinal dysraphism have been studied with phase MRI to assess longitudinal cord motion. Seventeen children who were asymptomatic and who had normal or slightly decreased motion were not operated. Fifteen had signs and symptoms of spinal cord tethering as well as decreased cord motion and underwent surgery. None of the nonsurgical patients have become symptomatic. The children with markedly decreased cord motion did not improve after surgery. A trend was seen toward a better outcome in younger patients with slight or moderate decrease in cord motion. All children with worse outcome were previously operated meningomyeloceles who had markedly decreased cord motion and who were greater than 10 years old. PMID- 7786804 TI - Electrophysiological studies on brainstem function in patients with myelomeningocele. AB - We investigated the brainstem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and electrically elicited blink reflexes (BRs) to evaluate the brainstem function in 31 patients with meyelomeningocele (MMC) including 22 with Chiari type-II malformation. The I-III interpeak latency (IPL) of the BAEPs and the N9-N13 IPL of the SEPs tended to become gradually prolonged from the normal range with increasing age. The III-V IPL of the BAEPs and the N13 N20 IPL of the SEPs were initially prolonged and decreased progressively to the normal range. These findings indicated a gradual latency shortening of the brainstem components and latency prolongation of the peripheral components. Thus, while primary brainstem dysfunction may improve with age, secondary dysfunction due to stretching and elongation of the lower cranial nerves and cervical nerve roots may intensify. The BRs showed an abnormal R2 in 90% of the cases, disclosing subclinical lesions in the medulla oblongata which were not detected by BAEPs alone. BAEPs, SEPs and BRs were combined to yield a functional evaluation of the brainstem and lower cranial nerves that could not be done by magnetic resonance imaging alone. No close relation was found between electrophysiological abnormalities and the degree of hindbrain anomaly by neuroimaging. PMID- 7786805 TI - Contemporaneous shunting with repair of myelomeningocele. AB - The combination of overt hydrocephalus and an open myelomeningocele in a newborn has prompted some authors to advocate the repair of the myelomeningocele and the performance of a shunt procedure during the same anesthetic procedure. Advocates of this approach stress the merits of administering only one anesthetic, diminution in incidence of cerebrospinal fluid leaks from the repair, and shortened hospital stay and the resultant cost-effectiveness. This study was performed to assess the complication rate of shunts inserted at the time of myelomeningocele repair as well as of those inserted at a later date as a separate procedure. It would later appear that the insertion of a ventriculoperitoneal shunt, contemporaneous with the repair of the myelomeningocele, does not increase the risks of shunt infection or shunt malfunction within the 1st year of life. PMID- 7786806 TI - Reflections on the natural history of lipomyelomeningocele. AB - A retrospective analysis of patients with lipomyelomeningocele cared for at two referral centers was completed to derive relationships between neurological function and patient age. Thirty-seven percent of 177 patients had intact neurological function on initial examination. Neurological deficits were progressive and linked with a logarithmic relationship to increasing patient age. Each child with intact examination retained normal bladder function following lipomyelomeningocele repair and release of cord tethering; complications of surgery were limited. Our analysis suggests that surgery on patients with intact function offers greater long-term protection of critical function than is offered by conservative management and expectant care. We recommend repair of lipomyelomeningocele at the time of diagnosis regardless of patient age or neurological function. PMID- 7786807 TI - Radiographic imaging requirements following ventriculoperitoneal shunt procedures. AB - The requirements for radiographic imaging of the ventricles after a ventricular shunt procedure are not well defined. At British Columbia's Children's Hospital, the standard protocol included an ultrasound examination or CT scan at 6-8 weeks postoperatively, and a delayed CT scan at 6 months to 2 years, with additional scans only if the patient had symptoms of shunt malfunction. This study was performed to determine if the delayed scan could be omitted without compromising patient care. The study comprised 86 children with ventriculoperitoneal shunt operations, who had early CT scans or ultrasound examinations less than 20 weeks postoperatively, delayed postoperative CT scans between 20 weeks and 2 years, and who were asymptomatic at the time of these radiographic studies. In 39 of the 86 patients a change in ventricular size occurred between the early and delayed imaging studies, and in these patients the delayed scan was felt to be required. In patients in whom the early imaging study was done at more than 12 weeks postoperatively, and probably in patients with small ventricles preoperatively, there was no added information gained by doing a delayed scan. It is concluded that a radiographic examination of ventricular size at 12 weeks after a shunt operation may provide an adequate baseline study. If the early postoperative radiographic study is done less than 12 weeks after surgery, we would advise that in asymptomatic patients, with the exception of patients with very small ventricles preoperatively, a CT scan be repeated at a later date to obtain an appropriate baseline assessment of ventricular size for the future. PMID- 7786809 TI - Spinal intradural arteriovenous fistula: a case with an unusual presentation. AB - Spinal intradural arteriovenous fistula is a rare type of spinal vascular malformation. It is usually fed by the anterior spinal artery and causes episodic myelopathy in young adults. We present a pediatric patient with such a vascular malformation which was fed directly by a medullary artery. The clinical course, complete radiological study and the excellent outcome will be described in detail. This rare subtype of spinal vascular malformation will be discussed. PMID- 7786808 TI - Pediatric cervical spine instrumentation using screw fixation. AB - From July 1986 to August 1993 we performed 24 pediatric cervical spine screw fixation procedures on 23 patients 16 years of age or less. The types of cervical instrumentation procedures performed were as follows: anterior cervical plates 12, posterior C1-2 screw fixations 8, posterior lateral mass plates 2, odontoid screw fixations 2. The mean age of all patients was 14.2 years (range 6-16). Indications for operation included traumatic instability in 20 cases, congenital instability in 1 case, 2 cases of postoperative swan neck deformity, and one reoperation for early graft and hardware failure. Six of the 23 patients had persistent instability following previous failed fusions (3 with 1 prior surgery, 2 with 2 prior surgeries, and 1 with 3 prior surgeries). Eight patients had improvement of their neurological status following operation and 15 remained at their preoperative level of neurological function. No patient was worse neurologically after their procedure. There were no long-term instrumentation, graft or fusion failures. Two complications occurred. One was the aforementioned graft and hardware failure requiring reoperation, the other was a superficial wound infection treated successfully with antibiotics. We feel that cervical spine fixation techniques have increased our ability to stabilize the pediatric cervical spine and have proven to be safe and effective. PMID- 7786810 TI - The Sunrise Technique: the correction of occipital plagiocephaly using bandeau occipital plate and radial osteotomies. AB - Posterior plagiocephaly secondary to lambdoid suture stenosis requires surgical release and repair to prevent progressive deformational changes associated with a suture stenosis. A surgical technique is described for release of the stenosed lambdoid suture and asterion region, followed by occipital reconstruction. This technique provides excellent cosmetic results. Using a standard biparietal incision, most of the occipital bone is removed en bloc. The asymmetric occiput is then reconstructed using an autologous bone bandeau and Marchac forehead template graft. The remaining bone is cut into longitudinal strips and placed in a centrifugal fashion around this construct. This technique creates a stable unit that provides immediate symmetry to the occipital area. The operative time and blood loss are comparable to that of similar procedures. With this technique there have been no complications or need for reoperation. PMID- 7786811 TI - Automated grading of astrocytomas based on histomorphometric analysis of Ki-67 and Feulgen stained paraffin sections. Classification results of neuronal networks and discriminant analysis. AB - In stereotactically obtained astrocytoma biopsies, four morphometric nuclear parameters were determined with the use of an image analysis system. A special Ki 67 (MIB1)/Feulgen stain made it possible to quantify the essential characteristics of gliomas of the astrocytoma/glioblastoma group: growth pattern, cellularity, proliferation tendency and nucleus pleomorphism. A grading scale based on a cluster analysis resembling the WHO-scheme, which is suitable for automated astrocytoma grading, was developed. Large back propagation neural networks were used and their results compared with those of a classical multivariate discriminant classification analysis. It is possible to show that the neural network technology is superior to the statistical approach for automated astrocytoma grading. Based on the results of our study we believe neural network technology to be useful for tumour grading problems. The presented approach can be generalized for the automated grading of other tumour entities. PMID- 7786812 TI - Grading of transitional cell bladder carcinoma by image analysis of histological sections. AB - Image analysis of histological sections was used to achieve a more objective malignancy grading of transitional cell carcinoma of the bladder. Images from Feulgen-stained sections from a clinical material of 197 tumours were analyzed. Features at various levels of analysis, e.g. mainly related to individual objects, neighbouring objects and the entire image, were analyzed. The features used were based on relational rather than individual nuclear features. With this technique, typical tissue architecture and degree of order/disorder can be described. These characteristics were compared by means of multivariate statistical methods with the subjective grading of the pathologists at our institution. This comparison provided the best subset of features and the agreement between the subjective and computer-based classification was 73%. The size, orientation and variation of the grey scale of the nuclei were particularly powerful. On a continuous scale, from grade 1 to 2A and 2B to 3, the four grades formed two distinct classes, low and high grade. In this distribution, the intermediate grade 2A was identified as a displaced grade 1 and the other intermediate grade 2B as a displaced grade 3. PMID- 7786813 TI - Changes in the activities of signal transduction and transport membrane enzymes in CEM lymphoblastoid cells by glucocorticoid-induced apoptosis. AB - The behaviour of the membrane enzymes PIP2-phospholipase C (PLC), that modulates the extracellular signals, and gamma-glutamyltransferase (gamma-GT), involved in metabolite transport, was followed during the early and active phases of apoptosis induced in CCRF-CEM cells by glucocorticoid (10(-6) M dexamethasone, DEX). The activities of gamma-GT and PLC increased significantly at 15 and 30 s after dexamethasone addition. Both activities decreased to the control level after 2 min but increased again at 5 min. The enzyme activities were high in apoptotic cells. Apoptosis was seen after incubation with 10(-6)M dexamethasone for 48 h, with decreased cell number, cellular activation (MTT) and S-phase percentage; enhanced DNA fragmentation and propidium iodide uptake; and ultrastructural changes in the chromatin and cell membranes. The changes in enzyme activity are indicators which occur much earlier than the cellular events related to the apoptotic death in CD4(+)-T CEM lymphoblastoid cells. PMID- 7786815 TI - Topoisomerase I inhibition: a new target or new missiles? PMID- 7786817 TI - Critique of the critique: response to the editorial entitled 'Classification of lymphoid neoplasms' by Dr. Saul Rosenberg which accompanied the publication of the 'Revised European-American Lymphoma Classification Proposal' in the September 1994 issue of Blood. PMID- 7786814 TI - Decreased E-cadherin expression correlates with poor survival in patients with gastric cancer. AB - E-cadherin, Ca(2+)-dependent intracellular adhesion molecule, is known to be an invasion suppressor gene. To elucidate the correlation between E-cadherin expression and invasion or metastasis in gastric cancer, we examined E-cadherin tissue status immunohistochemically. Ninety-eight primary gastric cancer, prepared by AMeX method, were retrospectively analyzed with anti-E-cadherin monoclonal antibody. In normal gastric epithelium, E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased and heterogeneous expression is found in 70 of 98 tumours. Tumours with decreased E-cadherin expression had a tendency to infiltrate more deeply in stomach wall, and metastasize in lymph nodes or peritoneal surface. More importantly, decreased E-cadherin expression correlates with shorter survival (z = 3.98, P = 0.00086). These results may indicate that E-cadherin tissue status is a powerful prognostic indicator in gastric cancer. The high malignant potential of tumours with decreased E-cadherin expression may be associated with high potential of lymph node metastasis and peritoneal dissemination. PMID- 7786816 TI - Current position of vinorelbine in cancer chemotherapy. PMID- 7786818 TI - The treatment of advanced bladder cancer. PMID- 7786819 TI - Tamoxifen chemoprevention: public health goals, toxicities for all and benefits to a few. PMID- 7786820 TI - Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. AB - BACKGROUND: CPT-11 (irinotecan) is a semi-synthetic derivative of camptothecin and exerts its activity by inhibiting DNA topoisomerase I. A phase II study of this drug was performed in patients with pancreatic cancer. PATIENTS AND METHODS: Eligibility criteria included advanced non-chemotherapy-pretreated pancreatic cancer. CPT-11 was administered as a 30-minute i.v. infusion at a dose of 350 mg/m2 diluted in 250 ml normal saline every 3 weeks. RESULTS: Thirty-four eligible patients were enrolled in the study, thirty-two of them were evaluated, and three achieved partial responses (9%; 95% C.I. = 3%-25%). The duration of response was 7.2, 7.5 and 7.8 months, respectively. Thirteen patients had no change, fourteen patients had progressive disease and two had early progressive disease. The median duration of survival for all patients treated was 5.2 months. The main toxicities (CTC grade > or = 3) were diarrhea, leukocytopenia, asthenia, nausea and vomiting in, respectively, 7%, 16%, 8%, 6%, 4% of the courses. These toxicities were reversible and manageable with anti-emetics and prophylactic or curative antidiarrheal agents. CONCLUSION: CPT-11 is an interesting moderately effective drug in pancreatic cancer. PMID- 7786822 TI - Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. AB - BACKGROUND: Irinotecan (CPT-11) is a novel water-soluble camptothecin derivative selected for clinical testing based on its good in vitro and in vivo activity in various experimental systems, including pleiotropic drug-resistant tumors. Its mechanism of action appears mediated through topoisomerase I inhibition. The purpose of this study was to describe CPT-11 and active metabolite SN-38 population pharmacokinetics, examine patient characteristics that may influence pharmacokinetics, and to investigate pharmacokinetic-pharmacodynamic relationships that may prove useful in the future clinical management of this drug. PATIENTS AND METHODS: As part of 3 Phase I studies including 235 patients, pharmacokinetics of CPT-11 and metabolite SN-38 were determined in 107 patients. CPT-11 was administered as a 30-min i.v. infusion according to 3 different schedules: daily for 3 consecutive days every 3 weeks, weekly for 3 weeks, and once every 3 weeks. Patients characteristics were the following: median age 53 years; 62 men, 45 women; 105 caucasians, 2 blacks; performance status was 0-1 in 96 patients; tumor sites were predominantly colon, rectum, head and neck, lung, ovary and breast; with the exception of 6 patients, all had been previously treated with surgery, chemotherapy and/or radiotherapy. CPT-11 and metabolite SN 38 were simultaneously determined by HPLC using fluorescence detection. Pharmacokinetic parameters were determined using model-independent and model dependent analyses. RESULTS: 168 pharmacokinetic data sets were obtained in 107 patients (97 first courses, 43 second courses, 23 third courses, 4 fourth courses, and 1 fifth course). Rebound concentrations of CPT-11 were frequently observed at about 0.5 to 1 h following the end of the i.v. infusion, which is suggestive of enterohepatic recycling of the drug. Model-independent analysis yielded the following mean population pharmacokinetic parameters for CPT-11: a terminal half-life of 10.8 h, a mean residence time (MRT) of 10.7 h, a volume of distribution at steady state (Vdss) of 150 L/m2, and a total body clearance of 14.3 L/m2/h. Model-dependent analysis disclosed a CPT-11 plasma disposition as either biphasic or triphasic with a mean terminal half-life of 12.0 h. The volume of distribution Vdss (150 L/m2) and total body clearance (14.8 L/m2/h) yielded almost identical values to the above model-independent analysis. The active metabolite SN-38 presented rebound concentrations in many courses at about 1 h following the end of the i.v. infusion which is suggestive of enterohepatic recycling. The mean time at which SN-38 maximum concentrations was reached was at 1 h since the beginning of the 0.5 h infusion (i.e., 0.5 h post i.v.). SN-38 plasma decay followed closely that of the parent compound with a mean apparent terminal half-life of 10.6 h. Mean 24 h CPT-11 urinary excretion represented 16.7% of the administered dose, whereas metabolite SN-38 recovery in urine was minimal (0.23% of the CPT-11 dose). The number of CPT-11 treatments did not influence pharmacokinetic parameters of either the parent compound or metabolite SN-38. Although CPT-11 pharmacokinetics presented an important interpatient variability, both CPT-11 maximum concentrations (Cmax) and the CPT-11 area under the plasma concentration versus time curves (AUC) increased proportionally and linearly with dosage (Cmax, r = 0.78, p < 0.001); CPT-11 AUC, r = 0.88, p < 0.001). An increase in half-life and MRT was observed at higher dosages, although this did not influence the linear increase in AUC as a function of dose. The volume of distribution at steady state (Vdss) and the total body clearance (CL) were not affected by the CPT-11 dose. Metabolite SN-38 AUC increased proportionally to the CPT-11 dose (r = 0.67, p < 0.001) and also with the parent compound AUC (r = 0.75, p < 0.001) (ABSTRACT TRUNCATED) PMID- 7786821 TI - Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. AB - BACKGROUND: We conducted a phase I and pharmacokinetic study to determine the maximum tolerable dose (MTD), toxicities, pharmacokinetic profile, and antitumor activity of Irinotecan (CPT-11) in patients with refractory solid malignancies. PATIENTS AND METHODS: Forty-six patients were entered in this phase I study. CPT 11 was administered intravenously over 30 minutes for 3 consecutive days every 3 weeks. Dose levels ranged from 33 mg/m2/day to 115 mg/m2/day on days 1 through 3. The pharmacokinetics of total CPT-11 and its active metabolite SN-38 were assayed by HPLC. RESULTS: The combination of leukopenia and diarrhea was dose-limiting toxicity at 115 mg/m2/day dose level, since 50% of the patients (5/10) experienced either grade 3-4 leukopenia, or diarrhea, or both. Leukopenia appeared to be a cumulative toxicity, with a global increase in its incidence and severity upon repeated administration of CPT-11. Other toxicities included nausea, vomiting, fatigue and alopecia. CPT-11 and active metabolite SN-38 pharmacokinetics were determined in 21 patients (29 courses). Both CPT-11 and SN 38 pharmacokinetics presented a high interpatient variability. CPT-11 mean maximum plasma concentrations reached 2034 ng/ml at the MTD (115 mg/m2). The terminal-phase half-life was 8.3 h and the mean residence time 10.2 h. The mean volume of distribution at steady state was 141 l/m2/h. CPT-11 rebound concentrations were observed in many courses at about 0.5 to 1 hour following the end of the i.v. infusion, which is suggestive of enterohepatic recycling. Total body clearance did not vary with increased dosage (mean = 14.3 l/h/m2), indicating linear pharmacokinetics within the dose range administered in this trial. The total area under the plasma concentration versus time curve (AUC) increased proportionally to the CPT-11 dose. Mean metabolite SN-38 peak levels reached 41 ng/ml at the MTD. A significant correlation was observed between CPT 11 area under the curve (AUC) and its corresponding metabolite SN-38 AUC (r = 0.52, p < 0.05). SN-38 rebound concentrations were observed in many courses at about 0.5 to 1 hour following the end of the i.v. infusion, which is suggestive of enterohepatic recycling. Mean 24-h urinary excretion of CPT-11 accounted for 10% of the administered dose by the third day, whereas SN-38 urinary excretion accounted for 0.18% of the CPT-11 dose. In this phase I trial, the hematological toxicity correlated with neither CPT-11 nor SN-38 AUC. Diarrhea grade correlated significantly with CPT-11 AUC. Two partial (breast adenocarcinoma and carcinoma of unknown primary) and 2 minor (hepatocarcinoma and pancreatic adenocarcinoma) responses were observed. CONCLUSION: The MTD for CPT-11 administered in a 3 consecutive-days-every-3 weeks schedule in this patient population is 115 mg/m2/day. The recommended dose for phase II studies is 100 mg/m2/day. PMID- 7786823 TI - Early versus late alternating chemotherapy in small-cell lung cancer. Swiss Group for Clinical Cancer Research (SAKK). AB - BACKGROUND: From 1984 to 1989, the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial comparing early versus late alternating chemotherapy in patients with small-cell lung cancer. PATIENTS AND METHODS: 406 eligible patients were entered into the trial. Regimen A consisted of PAV (cisPlatin, Adriamycin, VP 16-213, and Regimen B of CyMOC (Cyclophosphamide, Methotrexate, Oncovin, CCNU). Cycles were repeated as rapidly as possible. patients were randomized to receive either ABABAB (early alternating chemotherapy) or AAABBB (late alternating chemotherapy). After six cycles patients with limited disease in complete or partial remission and those with extensive disease in complete remission received irradiation to the primary (45 Gy) and the CNS (36 Gy). RESULTS: The overall remission rate was 87% with 31% complete remissions. The median survival of all 406 eligible patients was 346 days with 15% of the patients alive at two years. The overall remission rate, the rate of complete remission, the median survival and the rate of long-term survival were not significantly different in the two treatment arms. In limited disease the estimated percentages of survival at 2 years were 33% in the early and 24% in the late alternating chemotherapy arms. Patients with extensive disease survived significantly longer with late alternating chemotherapy than on the early alternation regimen (median survival 336 days versus 301 days, p = 0.01). In the latter patients the received dose intensities (RDI) of cisplatin, adriamycin and etoposide were significantly higher in the late-alternation arm. Patients treated with early alternating chemotherapy rated their tumor symptoms, functional states, fatigue/malaise and restriction of social activity significantly better, reflecting an improved subjective adjustment. CONCLUSIONS: Alternating chemotherapy with PAV-CyMOC plus consolidating radiotherapy is a feasible and effective treatment for small-cell lung cancer, with acceptable toxicity. Whereas patients with early alternating chemotherapy achieve a better subjective adjustment, late alternating chemotherapy allows for a higher RDI of cisplatin, adriamycin and etoposide, which results in a significantly longer median survival of patients with extensive disease. PMID- 7786824 TI - ChlVPP therapy for Hodgkin's disease: experience of 960 patients. The International ChlVPP Treatment Group. AB - BACKGROUND: Combination chemotherapy or combined chemo-radiotherapy is the treatment of choice for patients with advanced stage Hodgkin's disease and for patients failing curative radiotherapy. Increasingly, particularly in Europe, patients with early stage disease with poor prognostic features are also primarily treated with chemotherapy or combined chemo-radiotherapy. We analyzed the experience of 4 research groups which used ChlVPP, with or without radiotherapy, as standard chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Patients with Hodgkin's disease were treated with ChlVPP chemotherapy: days 1-14: chlorambucil: 6 mg/m2/day, procarbazine: 100 mg/m2/day, prednisone or prednisolone: 40 mg/day; Days 1, 8: vinblastine: 6 mg/m2/day. The use of radiotherapy varied across research groups, with many, but not all, patients receiving radiotherapy. RESULTS: A total of 960 patients were treated. 60% were male, 25% were aged 50+, 59% had nodular sclerosis histology. Failure-free survival (time to first occurrence of progression, relapse after response or death from any cause) at 5 years by stage was: Stage I/IIA (231 patients), 75%; I/IIB (152 patients), 62%; IIIA (180 patients), 67%; IIIB/IV (397 patients), 51%. Adverse prognostic factors for all patients included age 50+ and 'B' symptoms. Patients aged 50+ of all stages did especially poorly on ChlVPP therapy. The 34 stage IIIB/IV patients with lymphocyte depleted histology also did poorly. CONCLUSIONS: These results compare favorably with other reported series. ChlVPP is an appropriate alternative to other chemotherapy regimens for some Hodgkin's disease patients, often with a reduced toxicity profile. Other chemotherapy may be preferred in patients greater than 50 years of age. PMID- 7786825 TI - A phase II trial of vinorelbine and thiotepa in metastatic breast cancer. AB - BACKGROUND: Vinorelbine as single-agent has achieved an overall response rate of > 20% as second-line treatment and 40%-50% as first-line treatment. The aim of this study was to evaluate the activity and toxicity of the combination of vinorelbine and thiotepa as second-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-three patients (31: anthracycline based chemotherapy, 16: high-dose epirubicin) were given vinorelbine 30 mg/m2 and thiotepa 12 mg/m2 d 1 and 8 every 21 days. RESULTS: Among the 32 evaluable patients two complete responses and seven partial responses were observed, for an overall response rate of 28% (C.I. 12-44). The median duration of response was 9 months and the median time to progression 6 months. Significant toxicity was primarily leukopenia (72%); anemia was also frequent (48%) as well as local phlebitis (39%). CONCLUSION: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines. PMID- 7786827 TI - Oregon approves assisted suicide measures. PMID- 7786826 TI - Phase I study of weekly high-dose cisplatin combined with long-term oral etoposide in advanced solid tumors. AB - BACKGROUND: In a previous phase I study we showed that single-agent cisplatin can be given weekly for six weeks at a dose of 80 mg/m2/wk. It has been suggested that etoposide has synergistic activity with cisplatin and the drug can be given orally continuously. We therefore performed a phase I study with weekly cisplatin combined with oral etoposide. PATIENTS AND METHODS: Nineteen patients with metastases of a solid tumor were entered in the study. Cisplatin was administered in hypertonic saline (NaCl 3%). Etoposide was administered as 50-mg capsules. RESULTS: The starting dose was cisplatin weekly at a dose of 70 mg/m2 for six weeks combined with daily oral etoposide at a dose of 50 mg. At the maximum tolerable dose of cisplatin 75 mg/m2/wk and etoposide 50 mg/m2 daily, leukocytopenia and thrombocytopenia were dose-limiting toxic effects which resulted in frequent treatment delays. Other toxicities were mild. Finally, a dose of cisplatin 70 mg/m2/wk weeks 1-2-3 and weeks 5-6-7 in combination with etoposide 50 mg orally days 1-15 and days 29-43 combined a high median cisplatin dose intensity of 52.5 mg/m2/wk with a good patient tolerance. CONCLUSION: It is feasible to administer frequently dosed cisplatin in combination with oral etoposide. Leukocytopenia and thrombocytopenia are dose-limiting toxicities. The schedule will be explored further in phase II studies. PMID- 7786828 TI - Survey on euthanasia in Britain. PMID- 7786829 TI - . . . and funding for cancer research must be transparent. PMID- 7786830 TI - French minister: "we badly need a cancer plan...". PMID- 7786831 TI - Preconditioning with a single short episode of global ischemia in the isolated working rat heart: effect on structure, mechanical function, and energy metabolism for various durations of sustained global ischemia. AB - PURPOSE: Preconditioning in the setting of global ischemia, using functional recovery during reperfusion as the endpoint, has recently been demonstrated in the isolated perfused rat heart. It has been suggested that its beneficial actions have a metabolic basis. The isolated rat heart has not been fully characterized with respect to the metabolic, functional, and structural changes associated with this phenomenon in the setting of global ischemia. The purpose of this study was to determine (1) the time course of protection conferred by a single episode (5 minutes) of preconditioning; (2) changes in tissue high energy phosphates, lactate, and glycogen levels at different time intervals; and (3) morphological appearance of the heart at the end of ischemia as well as after reperfusion. METHODS: Isolated perfused working rat hearts were used. Preconditioning consisted of a single episode of 5 minutes of global ischemia and 15 minutes of reperfusion. Preconditioned and non-preconditioned hearts were subjected to global ischemia of 20-35 minutes duration. Functional recovery, energy metabolism (high energy phosphates, lactate, and glycogen), and structural appearance were studied at different stages. RESULTS: The functional recovery of the preconditioned hearts was significantly higher than in the corresponding nonpreconditioned group during reperfusion for all durations of ischemia longer than 25 minutes. The degree of protection observed was less than reported previously. A minor degree of energy sparing was reflected by differences in the rate of depletion of glycogen and accumulation of tissue lactate during the sustained episode of ischemia. Semiquantitative light microscopy evaluation revealed that ischemia-induced structural damage was less in the preconditioned hearts, both at the end of the sustained ischemic episode as well as after reperfusion. CONCLUSIONS: A single episode of global ischemia successfully preconditions the isolated working rat heart. The protection elicited was demonstrated on a functional and structural level, and was accompanied by a small energy-sparing effect. PMID- 7786832 TI - Effects of growth hormone in rats with postinfarction left ventricular dysfunction. AB - Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p < 0.05) and dP/dt (p < 0.05) and reduced left ventricular end-diastolic pressure (p < 0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure. PMID- 7786833 TI - Effect of beta-blockade on exercise capacity in hypertensive subjects: a one-year double-blind study of celiprolol and metoprolol. AB - To assess the effect of beta-blocker antihypertensive therapy on exercise capacity, 40 patients randomized to celiprolol 200 mg and metoprolol 100 mg daily in a double-blind fashion were studied after a month of placebo and a year of active treatment. Both drugs normalized office blood pressure and produced echocardiographic and electrocardiographic left ventricular hypertrophy regression. In symptom-limited maximal stress tests before and after treatment, exercise duration increased with (p < 0.0001) celiprolol (513-700 seconds) and metoprolol (520-634 seconds), although more with the former (p = 0.02). Resting heart rate was reduced with both, more with metoprolol (p < 0.001), while heart rate at peak exercise was reduced similarly with both medications (p < 0.005). Blood pressure at peak exercise was reduced with both celiprolol (217-184 mmHg; p = 0.0002) and metoprolol (218-185 mmHg, p < 0.0001) to a similar degree (p = NS). Exercise parameters were not related to patient age or the degree of left ventricular hypertrophy regression (p = NS). It is concluded that beta-blocker antihypertensive therapy improves exercise capacity, decreasing heart rate and blood pressure responses to stress, irrespective of left ventricular structural changes. PMID- 7786834 TI - Comparative effects of fosinopril and nifedipine on regression of left ventricular hypertrophy in hypertensive patients: a double-blind study. AB - The effects of fosinopril and nifedipine on left ventricular (LV) mass were evaluated in 35 hypertensive patients with LV mass index greater than 110 g/m2 in female and 130 g/m2 in male patients. The goal of therapy was also to obtain a seated diastolic blood pressure (SDBP) of less than 90 mmHg. The patients were studied by echocardiography after 2 weeks of placebo treatment and 4, 12, and 24 weeks of monotherapy with active drugs. Both fosinopril and nifedipine reduced SDBP to a normal level after 6 months of treatment (p < .001). Regression of LV hypertrophy was achieved by either agent (p < .001), with fosinopril being more effective than nifedipine (p < .002). In conclusion, both fosinopril and nifedipine effectively reduce SDBP and achieve important regression of LV hypertrophy. PMID- 7786835 TI - "Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. AB - Despite the findings in randomized trials of a significant effect of angiotensin converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of a aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may "escape" despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor. PMID- 7786836 TI - Distinct modulation of myocardial performance, energy metabolism, and [Ca2+]i transients by positive inotropic drugs in normal and severely failing hamster hearts. AB - The present study compared the effects of amrinone, dobutamine, dibutyryl cAMP, digoxin, and isoproterenol on mechanical performance, the high energy phosphate metabolites, and the [Ca2+]i transients in normal and cardiomyopathic hamster hearts with severe heart failure. In normal hearts dobutamine, dibutyryl cAMP, and isoproterenol increased left ventricular developed pressure, while amrinone and digoxin did not. However, the amplitude of [Ca2+]i transients was augmented with all drugs. Diastolic [Ca2+]i level was increased with dobutamine and lowered with dibutyryl cAMP and isoproterenol. In cardiomyopathic hearts with severe heart failure, left ventricular developed pressure, the amplitude of [Ca2+]i transients, the phosphorylation potential, and [cAMP]i were significantly depressed and left ventricular end-diastolic pressure and diastolic [Ca2+]i were significantly elevated when compared with normal hearts. Amrinone, dibutyryl cAMP, and isoproterenol improved mechanical performance while increasing [cAMP]i and the amplitude of [Ca2+]i transients, and decreasing diastolic [Ca2+]i. On the other hand, with dobutamine and digoxin diastolic [Ca2+]i was further increased and mechanical performance deteriorated with digoxin. Thus, distinct differences exist in modulation of mechanical performance, high-energy phosphate metabolism, and [Ca2+]i transients by positive inotropic drugs between normal and cardiomyopathic hearts with severe heart failure. PMID- 7786837 TI - Muscarinic receptors and drugs in cardiovascular medicine. AB - The parasympathetic system and its associated muscarinic receptors have been the subject of a renaissance of interest for the following two main reasons: (1) the association of endothelial muscarinic receptors and the nitric oxide (NO) pathway; (2) the discovery of several muscarinic receptor subtypes and drugs interacting with them. In the present survey modern insights into the subdivision of muscarinic receptors have been dealt with as the basis for a description of the muscarinic receptor agonists and antagonists thus far known. There are at least four pharmacologically defined M receptors (M1, M2, M3, M4) in primary tissues, and five muscarinic receptors have been cloned (m1, m2, m3, m4, m5). Selective agonists for M-receptor subtypes hardly exist, and all classical agonists (acetylcholine, carbachol, etc.) are clearly nonselective. A few selective antagonists for M1 (pirenzepine) and M2 receptors (AF-DX 116) have been introduced, although selective M3 receptors are hardly available. Finally, the potential therapeutic use of M-receptor agonists (myocardial ischemia, hypertension) and muscarinic antagonists (certain forms of bradycardia, coronary spasm) has been critically discussed. Although only in a preliminary stage, this development appears to be promising and at least of great fundamental interest. PMID- 7786838 TI - Elastic properties and Windkessel function of the human aorta. AB - An understanding of the role of the aortic elastic properties indicates their relevance at several sites of cardiovascular function. Acting as an elastic buffering chamber behind the heart (the Windkessel function), the aorta and some of the proximal large vessels store about 50% of the left ventricular stroke volume during systole. In diastole, the elastic forces of the aortic wall forward this 50% of the volume to the peripheral circulation, thus creating a nearly continuous peripheral blood flow. This systolic-diastolic interplay represents the Windkessel function, which has an influence not only on the peripheral circulation but also on the heart, resulting in a reduction of left ventricular afterload and improvement in coronary blood flow and left ventricular relaxation. The elastic resistance (or stiffness), which the aorta sets against its systolic distention, increases with aging, with an increase in blood pressure, and with pathological changes such as atherosclerosis. This increased stiffness leads to an increase in systolic blood pressure and a decrease in diastolic blood pressure at any given mean pressure, an increase in systolic blood velocity, an increase in left ventricular afterload, and a decrease in subendocardial blood supply during diastole, and must be considered a major pathophysiological factor, for example, in systolic hypertension. The elastic properties of the aortic Windkessel can be assessed in vivo in humans in several ways, most easily by measuring the pulse wave velocity along the aorta. The higher this velocity, the higher the elastic resistance, that is, the stiffness. Other methods depend on assessment of the ratio between pulse pressure and aortic volume changes (delata P/delta V), which can be assessed noninvasively by ultrasonic or tomographic methods. All assessments of vessel stiffness have to take into account the direct effect of current blood pressure, and thus judgements about influences of interventions rely on an unchanged blood pressure. Alternatively, to derive the "intrinsic" stiffness of the aortic wall one has to correct for the effect of the blood pressure present. Recently reports about pharmacologic influences on the elastic properties of the aorta have emerged in the literature.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7786840 TI - Reduction of ischemic events with angiotensin-converting enzyme inhibitors: lessons and controversy emerging from recent clinical trials. AB - Angiotensin-converting enzyme (ACE) inhibitor therapy has been associated with a substantial (> or = 20%) reduction in the risk of major ischemic events in two recent clinical trials with long-term follow-up: Studies of Left Ventricular Dysfunction (SOLVD) and the Survival and Ventricular Enlargement (SAVE) study. Participants in these studies included patients with a low ejection fraction (< or = 0.35 in SOLVD and < or = 0.40 in SAVE), generally without symptoms of congestive heart failure. Approximately 80% of patients enrolled in SOLVD and all participants in SAVE had histories of ischemic heart disease or acute myocardial infarction (SAVE). In both SOLVD and SAVE the risk of experiencing a major ischemic event such as myocardial infarction was reduced significantly following prolonged ACE inhibitor therapy. In the SOLVD trial, this effect was evident across a range of patient subgroups, including varying concomitant drug therapies. In both studies, several months elapsed before this benefit became apparent, suggesting an effect on underlying ischemic pathophysiology. A third trial of ACE inhibitor therapy postinfarction, the Acute Infarction Ramipril Efficacy (AIRE) Study, demonstrated a 27% reduction in all cause mortality but no effect on myocardial infarction after a 15-month mean follow-up. No effect of ACE inhibition on risk of survival or reinfarction was reported in the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS-II), which began the drug within 24 hours of infarction and terminated follow-up at 6 months, a time not likely to demonstrate infarction reduction benefit based on the SOLVD and SAVE observations. Neither AIRE nor CONSENSUS-II had objectively determined left ventricular dysfunction as an entry criterion, as did SOLVD and SAVE, but AIRE mandated "clinical" congestive heart failure prior to randomization. More recently, preliminary results from the third Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3), the Fourth International Study of Infarct Survival (ISIS-4), and the Chinese Captopril Trial suggested that angiotensin-converting enzyme (ACE) inhibitor mortality benefits post-myocardial infarction would be detected in these megatrials as early as 35 days after the event.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7786839 TI - Intravenous cibenzoline in the management of acute supraventricular tachyarrhythmias. AB - Intravenous cibenzoline was evaluated in 37 patients with acute supraventricular tachyarrhythmias and a ventricular rate > 120 beats/min. The presenting arrhythmia was atrial fibrillation in 15 patients, atrial flutter in 5, ectopic atrial tachycardia in 11, and paroxysmal atrioventricular (AV) junctional reentrant tachycardia in 6 patients. Intravenous cibenzoline was administered as a bolus given over 2 minutes, at a dose of 1 mg/kg in the first 26 patients and 1.2 mg/kg in the subsequent 11 patients, 15 minutes following failure of placebo (isotonic glucose). The results were evaluated 15 minutes after the intravenous injection. Restoration of sinus rhythm was obtained in 3 out of 6 patients with paroxysmal AV junctional tachycardia (50%) and in 7 out of 31 patients (23%) with atrial tachyarrhythmias (5 out of 15 patients with atrial fibrillation and 2 out of 16 patients with ectopic atrial tachycardia or atrial flutter). Five additional patients with atrial tachyarrhythmias had slowing of ventricular rate below 100 beats/min. Therefore, a satisfactory result, that is, restoration of sinus rhythm or slowing of ventricular rate, occurred in 15 patients (40.5%). Side effects were transient, including visual disturbance (one patient), asymptomatic widening of QRS complex (three patients), incessant reciprocating tachycardia (one patient), and acceleration of ventricular rate (eight patients), resulting in 1:1 flutter, with poor tolerance in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786841 TI - Adaptation aftereffects in single neurons of cat visual cortex: response timing is retarded by adapting. AB - Extracellular single-unit recordings were made from simple cells in area 17 of anesthetized cats. Cells were tested with drifting gratings under control and adapted conditions. Response amplitude and phase were measured as a function of either contrast or temporal frequency. Adapting not only reduces amplitude, but also retards phase. Adaptation alters the responses of simple cells in a particular way: the onset of the response to each cycle of a sinusoidally modulate stimulus is delayed. Once cells start to respond during each cycle, however, they generally recover to control levels, and the offset of the response is unaffected by adapting. The timing aftereffects are independent of the amplitude aftereffects. Timing aftereffects are tuned around the adapting temporal frequency, with a bias toward lower temporal frequencies. Adaptation thus modifies cortical responses even more specifically then previously thought. Firing rates are depressed primarily at response onset, even after several stimulus cycles have occurred following the end of adapting. Because all cells appear to adapt in this way, the data offer an opportunity to theorize about cortical connectivity. One implication is that inhibition onto a simple cell arises from other simple cells with similar response properties that fire a half cycle out of phase with the target cell. PMID- 7786842 TI - How task-related are the responses of inferior temporal neurons? AB - The responses of inferior temporal (IT) neurons may depend on the behavioral context of the stimuli; e.g. in Konorski tasks responses to two successively presented physically identical stimuli can be markedly different. This effect has been interpreted as being linked to the behavioral task, and to be involved in short-term memory and/or the temporal comparison of successively presented stimuli. We tested whether this behavioral context effect also occurs when the monkey is not executing a Konorski task, i.e. no temporal comparison of stimuli is being performed. Responses of the same IT neurons under two behavioral conditions were compared using the same temporal stimulus sequence (but different stimuli): a Konorski task and a Fixation task. We found that the occurrence of the behavioral context effect did not depend on the execution of the short-term memory task. The observed decline in the level of responses to repeated presentation of similar stimuli is interpreted as being a passive mechanism involved in recency detection, which occurs even if the recency information is not useful for the task. The importance of these results in the interpretation of "task-related" neuronal responses is discussed. PMID- 7786843 TI - Expression of the proto-oncogene, trk, receptors in the developing rat retina. AB - The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 are important in a variety of developmental processes in the peripheral and central nervous systems. These molecules bind to a low-affinity receptor and to distinct high-affinity receptors. The high-affinity receptor for NGF is the proto-oncogene product, p140trkA(trkA). Isoforms of p140trkA, p145trkB(trkB), and p140trkC(trkC), are the primary high-affinity receptors for BDNF and NT-3, respectively. We evaluated the developmental regulation of the high-affinity neurotrophin receptors in the rat retina using polyclonal antibodies directed to a highly conserved region of the C terminus of the p140trkA isoforms (pantrk) and antibodies directed to unique amino-acid sequences of p140trkA, p145trkB, and p140trkC. Immunoreactivities for trkA and trkB, as well as pantrk, were detected in the developing retina and showed similar distributions. At similar antibody concentrations, trkC immunoreactivity was not detected. In the embryo, immunoreactivties were present in cells located throughout the neuroblastic retina, especially in the inner retinal layers, and in fibers in the nerve fiber layer and optic nerve. In the newborn retina, immunoreactivities for these two receptor isoforms were localized to numerous somata in the inner nuclear layer (INL), as well as to cells in the ganglion cell layer (GCL) and axons in the nerve fiber layer and optic nerve. A similar pattern of immunostaining persisted throughout the first postnatal week. By postnatal day-10, immunostaining was confined to large-diameter cells in the GCL, both heavily stained and lightly stained cells in the INL and a plexus of processes in the inner plexiform layer (IPL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786844 TI - The VEP thresholds for full-field stimuli in dark-adapted infants. AB - Dark-adapted adults' electroretinographic b-wave thresholds are approximately 2 log units below a-wave thresholds and approximately 3 log units above the perceptual threshold, and their perceptual and the visually evoked cortical potential (VEP) thresholds are similar. Dark-adapted infants' scotopic a- and b wave thresholds for full-field stimuli are both about 0.5 log units above those of adults, but their scotopic VEP thresholds for such stimuli have not been studied. We obtained scotopic VEP thresholds for brief, full-field stimuli from dark-adapted, infants and adults to consider the relationships of the cortical responses to the responses of more distal structures, namely the rod photoreceptors (scotopic a-wave) and ON-bipolars (scotopic b-wave). The median VEP threshold of infants is 0.5 log unit above that of adults. Thus, the relationships of a- and b-wave and VEP thresholds in infants are similar to those in adults. These results are consistent with rod cell immaturities being the primary determinant of the difference between infants' and adults' thresholds. PMID- 7786845 TI - Effects of wavelength on the timing and laminar distribution of illuminance evoked activity in macaque V1. AB - Responses to full-field colored flashes (red, blue, and green) were compared with those to illuminance-matched white flashes in area V1, optic radiations, and the lateral geniculate nucleus of two alert macaques. Laminar profiles of visual evoked potentials (VEPs), current source density, and multiunit activity were obtained using multicontact electrodes capable of sampling from all layers of cortex or lateral geniculate nucleus, simultaneously. In striate cortex, stimulation with colored flash enhanced transmembrane current flow dramatically in both layer 4c and the supragranular laminae. Stimulation with red evoked the largest enhancement in every electrode penetration. The mean peak amplitudes of current sinks evoked by red were 203% and 537% of those evoked by white light in layer 4c and the supragranular laminae, respectively. Color effects in V1 were preceded by an initial epoch of wavelength-insensitive activity. In layer 4c, the red effect reached significance, on average, at 47 ms, or approximately 24 ms after the onset of transmembrane current flow. In the supragranular layers, the red effect reached significance, on average, at 55 ms, or approximately 14 ms after the onset of current flow. Recordings from optic radiations in the white matter below V1 and from lateral geniculate nucleus showed no significant difference in the responses to color and illuminance-matched white light. Enhancement of supragranular current flow with color stimulation increased the contribution of these laminae to the generation of the surface VEP. Comparison of the surface VEP wave forms evoked by white and color stimuli may, therefore, help to differentiate the responses of the granular and supragranular laminae. PMID- 7786846 TI - Ultrastructural study of the optic nerve in blind mole-rats (Spalacidae, Spalax). AB - The optic nerve in two species of subterranean mole-rats (Spalacidae) has been examined at the ultrastructural level. The axial length of the eye and the diameter of the optic nerve are 1.9 mm and 52.5 microns in Spalax leucodon, and 0.7 mm and 80.8 microns in Spalax ehrenbergi, respectively. An anti-glial fibrillary acidic protein postembedding procedure was used to distinguish glial cell processes from axons. In both species, the optic nerve is composed exclusively of unmyelinated axons and a spatial distribution gradient according to the size or the density of fibers is lacking. The optic nerve of S. leucodon contains 1790 fibers ranging in diameter from 0.07-2.30 microns (mean = 0.57 microns), whereas in S. ehrenbergi, only 928 fibers, with diameters of 0.04-1.77 microns (mean = 0.53 microns) are observed. In S. ehrenbergi, a higher proportion of glial tissue is present and the fascicular organization of optic fibers is less obvious. Distribution gradients according to size frequency or density of fibers in the optic nerve are absent in both species. Comparison with other mammals suggests that although ocular regression in microphthalmic species is correlated with a significant decrease in the total number of optic fibers and the relative proportion of myelinated fibers, no difference in the absolute size range of unmyelinated axons is observed. The total absence of myelinated fibers in Spalax may be related to the subcutaneous location of the eyes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786848 TI - The glial ensheathment of the soma and axon hillock of retinal ganglion cells. AB - We have studied the glial investment of ganglion cells of the cat's retina, orienting the sections taken for electron microscopy so that the investment could be traced from the soma along the axon. The soma of each ganglion cell is covered by a close-fitting, continuous sheath formed by Muller cells. The axon hillock and the first part of the initial segment are invested by an extension of the somal sheath, and are thus enclosed in the same glial compartment as the soma. The initial segment extends a few microns past the Muller cell sheath; this last length of the initial segment is contacted by numerous processes of astrocytes, which converge on it in a pattern found also on nodes of the same axons, in the optic nerve. Beyond the initial segment, the intraretinal lengths of the axons are invested by both Muller cells and astrocytes, but the investment is strikingly incomplete. Large areas of axonal membrane have no glial cover, and lie close to other axonal membranes. The sequential arrangement of these distinct forms of glial wrapping of the soma, initial segment, and axon is described here for the first time. It is suggested that this pattern of glial investment controls the flow of current between dendrite and initial segment of the ganglion cell, defines the site of initiation of action spikes, and controls the formation of synapses on the soma and initial segment. PMID- 7786847 TI - Characterization and localization of an aldehyde dehydrogenase to amacrine cells of bovine retina. AB - An enzyme of bovine retina that catalyzes oxidation of retinaldehyde to retinoic acid was purified to homogeneity and a monoclonal antibody (mAb H-4) was generated. MAb H-4 recognized a single component (Mr = 55,000) in extracts of bovine retina and other bovine tissues. The antibody showed no cross-reactivity with extracts of rat, monkey, or human retinas. A 2067 bp cDNA was selected from a retina cDNA expression library using mAb H-4. The cDNA hybridized with a similarly sized, moderately abundant mRNA prepared from bovine retina. Nucleotide sequence analysis indicated that the cDNA contained a single open reading frame encoding 501 amino acids that have 88% sequence identity with the amino-acid sequence of human hepatic Class 1 aldehyde dehydrogenase. Amino-acid sequence analysis of purified enzyme demonstrated that the cDNA encodes the isolated enzyme. MAb H-4 specifically labeled the somata and processes of a subset of amacrine cells in bovine retinal sections. Labeled amacrine somata were located on both sides of the inner plexiform layer, and their processes ramified into two laminae within the inner plexiform layer. The inner radial processes of Muller (glial) cells were weakly reactive with mAb H-4. Weak immunostaining of amacrine cells was found in monkey retina with mAb H-4, but no signal was detected in rat or human retina. The results provide further evidence for metabolism and function of retinoids within cells of the inner retina and define a novel class of retinal amacrine cells. PMID- 7786850 TI - Receptive-field properties of Q retinal ganglion cells of the cat. AB - The goal of this work was to provide a detailed quantitative description of the receptive-field properties of one of the types of rarely encountered retinal ganglion cells of cat; the cell named the Q-cell by Enroth-Cugell et al. (1983). Quantitative comparisons are made between the discharge statistics and between the spatial receptive properties of Q-cells and the most common of cat retinal ganglion cells, the X-cells. The center-surround receptive field of the Q-cell is modeled here quantitatively and the typical Q-cell is described. The temporal properties of the Q-cell receptive field were also investigated and the dynamics of the center mechanism of the Q-cell modeled quantitatively. In addition, the response vs. contrast relationship for a Q-cell at optimal spatial and temporal frequencies is shown, and Q-cells are also demonstrated to have nonlinear spatial summation somewhat like that exhibited by Y-cells, although much higher contrasts are required to reveal this nonlinear behavior. Finally, the relationship between Q-cells and Barlow and Levick's (1969) luminance units was investigated and it was found that most Q-cells could not be luminance units. PMID- 7786849 TI - The cat's pupillary light response under urethane anesthesia. AB - Pupillary area was measured in urethane-anesthetized cats as a function of retinal illuminance. When appropriate corrections are made for differences in experimental procedures, it was found that the pupillary response of the urethane anesthetized cat's eyes to light was basically unchanged from that of the alert behaving cat. This preparation may therefore be a very satisfactory one in which to study the pupillary response pathway in a higher mammal. PMID- 7786851 TI - Calbindin D-28K immunoreactivity of human cone cells varies with retinal position. AB - Calbindin D-28K is a calcium-binding protein found in the cone but not rod photoreceptor cells in the retinas of a variety of species. Recent studies of the monkey retina indicated that calbindin D-28K may be expressed preferentially in non-foveal regions of the retina. In the current studies of human retinas, immunohistochemical experiments demonstrated that calbindin D-28K is reduced or absent in the fovea and parafovea, but prevalent in the perifovea and periphery. These findings were supported by the quantification of calbindin D-28K in 1-mm trephine punches obtained from different regions of the human retina. The specificity of the anti-calbindin D-28K antibodies used in these studies was confirmed by Western blot analysis using purified calbindin D-28K. The protein was purified from retinal tissue and its identity confirmed by partial amino-acid sequence analysis. The expression of calbindin D-28K did not correlate with the spectral properties of the cones, rather to their position in the retina. The study of spatially expressed genes, like the one encoding calbindin D-28K, may help explain the patterns of retinal degeneration seen in some human cone-rod dystrophies. PMID- 7786853 TI - Behavioral and neural effects of chromatic isoluminance in the primate visual motion system. AB - We have previously reported that the responses of individual neurons in macaque visual area MT elicited by movement of contrast-reversing heterochromatic red/green borders are largest when the two hues are "balanced" or isoluminant (Dobkins & Albright, 1994). This "neural" isoluminant point was found to vary somewhat across the sample of neurons. Here, we compare the average neural isoluminant point in area MT to a behavioral measure of isoluminance, obtained using a modification of an oculomotor procedure developed by Chaudhuri and Albright (1992). These behavioral estimates of isoluminance closely parallel the neuronal data obtained from area MT. In accordance with previous evidence (e.g. Lee et al., 1988; Kaiser et al., 1990; Valberg et al., 1992), this correlation suggests that activity within the dorsal/magnocellular stream underlies behavioral expression of chromatic isoluminance. PMID- 7786852 TI - The influence of input from the lower cortical layers on the orientation tuning of upper layer V1 cells in a primate. AB - The receptive fields of cells in the primary visual cortex (area 17 or V1) show clear orientation selectivity, unlike those of the lateral geniculate nucleus (LGN) cells which provide their visual input. The intrinsic circuitry of V1 cells is believed to be partly responsible for this selectivity. We investigated the influence of ascending projections from neurons in the lower layers (5 and 6) of V1 on the orientation selectivity of single neurons in the upper layers (2,3, and 4) by reversibly inactivating ("blocking") lower layer neural activity with iontophoretic application of gamma-aminobutyric acid (GABA) while recording from upper layer cells in the prosimian primate, Galago crassicaudatus. During lower layer blocking, the majority (20/28 = 71.4%) of upper layer neurons exhibited a change in the orientation of their preferred stimulus, a reduction in their orientation tuning, and/or an increase in their response amplitude. Twelve (42.9%) neurons exhibited shifts in their preferred orientation averaging 11 (+/- 4) deg. These neurons were located on average, 272 (+/- 120) microns tangential from the vertical axis of the pipette center. Eleven neurons (39.2%) exhibited an average reduced orientation tuning of 52.5%. Their average location was 230 +/- (115) microns away from the vertical axis of the pipette. Five (17.9%) neurons with average location 145 (+/- 75) microns from the vertical axis exhibited both effects. Two (7.1%) neurons that exhibited significant increases in response amplitude to stimulus angles within 10 deg of the peak excitatory stimulus without changes in orientation selectivity or tuning were located less than 100 microns from the vertical axis. The effects on the orientation tuning of cells were restricted in all cases to within +/- 30 deg of the preferred stimulus orientation. This suggests that layer blocking affects cells with preferred stimulus orientations similar to those of the recorded neurons. Only cells located within 500 microns tangential to the vertical axis of the injection site exhibited these effects. These results suggest that cells within layers 5 and 6 provide organized, orientation-tuned inhibition that sharpens the orientation tuning of cells in the upper cortical layers within the same, or closely neighboring, cell columns. PMID- 7786854 TI - Spectral properties of turtle cones. AB - Microelectrodes were used to record from red and green cones of the turtle Pseudemys scripta elegans. The purpose of this study was to determine the action spectra of the red and green cone photopigments, and to look closely for direct interactions between the two cone classes. An isolated retina preparation was employed so that cones could be stimulated from the outer segment side, thereby avoiding the oil droplets that reside in the inner segments of many cones and normally filter incident light. In agreement with some previous electrophysiological studies, we found little evidence for significant direct connections between red and green cones. Exceptions to this rule are noted and discussed. Measurements indicate that this result does not appear to be due to a general loss of cone connectivity in the isolated retina preparation. Action spectra of the cone photopigments differed markedly from action spectra reported for cones in the eyecup preparation. In contrast to cones in the eyecup, cones in the isolated retina showed higher short-wavelength sensitivity and had action spectra that were adequately described by photopigment nomograms. A model of cone optical properties suggests that in the eyecup up to about 40% of the light that reaches a cone outer segment may do so without first passing through an oil droplet. PMID- 7786855 TI - Co-stratification of GABAA receptors with the directionally selective circuitry of the rat retina. AB - Direction-selective (DS) ganglion cells of the mammalian retina have their dendrites in the inner plexiform layer (IPL) confined to two narrow strata. The same strata are also occupied by the dendrites of cholinergic amacrine cells which are probably presynaptic to the DS ganglion cells. GABA is known to play a crucial role in creating DS responses. We examined the types of GABAA receptors expressed by the cholinergic amacrine cells and also those expressed by their presynaptic and postsynaptic neurons, by applying immunocytochemical markers to vertical sections of rat retinas. Double-labelling experiments with antibodies against choline acetyltransferase (ChAT) and specific antibodies against different GABAA receptor subunits were performed. Cholinergic amacrine cells seem to express an unusual combination of GABAA receptor subunits consisting of alpha 2-, beta 1-, beta 2/3-, gamma 2-, and delta-subunits. Bipolar cells, which could provide synaptic input to the DS circuitry, were stained with antibodies against the glutamate transporter GLT-1. The axon terminals of these bipolar cells are narrowly stratified in close proximity to the dendritic plexus of displaced cholinergic amacrine cells. The retinal distribution of synaptoporin, a synaptic vesicle associated protein, was studied. Strong reduction of immunolabelling was observed in the two cholinergic strata. The anatomical findings are discussed in the context of models of the DS circuitry of the mammalian retina. PMID- 7786857 TI - Visual latencies in areas V1 and V2 of the macaque monkey. AB - Latencies to small flashing spots of light were measured in different layers of areas V1 and V2 in anesthetized and paralyzed macaque monkeys. The shortest latencies were found in layers 4C alpha and 4B of area V1. Latencies in layer 4C beta were on average 20 ms longer than those in 4C alpha and 4B. The shortest latencies in area V2 were observed in the infragranular layers and they did not differ significantly from those found in the infragranular layers in V1. Similarly, latencies in the supragranular layers of V2 were not significantly different from those measured in the supragranular layers of V1. These results show that, in area V1, neurons of the magnocellular pathway are activated on average 20 ms earlier than those of the parvocellular pathway. Our data also suggest that much processing begins simultaneously in areas V1 and V2. PMID- 7786856 TI - The occurrence of dopaminergic interplexiform cells correlates with the presence of cones in the retinae of fish. AB - Using light-microscopic immunocytochemistry against tyrosine hydroxylase, we have investigated the morphology of dopaminergic cells in 23 species of fishes representing various systematic classes and subclasses and which live in very different habitats. We have, for the first time, observed teleosts with dopaminergic amacrine cells. Thus, in both bony and cartilaginous fishes, dopaminergic cells are differentiated as interplexiform and amacrine cells. The differentiation of dopaminergic cells into amacrine or interplexiform cells in fishes correlates with the absence or presence of cones. In pure-rod retinae, they occur as amacrine cells, and in mixed rod/cone retinae, they occur as interplexiform cells. We conclude therefore that the differentiation of retinal dopaminergic cells in fish does not depend on the evolutionary or systematic classification of a given species. Rather, it is correlated with the occurrence of rods and/or cones, and thus linked more closely to the habitat. We argue that, in fish, the presence of cones and cone-specific horizontal cells may be responsible for inducing dopaminergic cells to differentiate as interplexiform cells. Possible functions of dopamine in all-rod retinae, which may not require adaptation, may include neuromodulation in the inner plexiform layer for the sensitization of the rod pathway, the shaping of biological rhythms, and the control of eye growth. PMID- 7786858 TI - Perceived length across the physiological blind spot. AB - Objects falling across the physiological blind spot appear "complete" despite the absence of photoreceptors. Completion of objects may occur across the blind spot because (1) the blind spot is filled in with the background (the associative explanation); (2) the opposite sides of the blind spot may be contiguously represented in the cortex (i.e. the blind spot is simply sewn up-the retinotopic explanation); or (3) the blind spot may be sewn up, with compensatory expansion occurring around the blind spot (the compensation explanation). These theories would predict no size distortions regardless of object size; constant size distortions regardless of object size; and distortions that depend on the size of the object, respectively. To evaluate these explanations, we measured size distortions at the blind spot. We measured length distortions at the blind spot using a criterion-free two-alternative forced-choice method with feedback. Observers compared the lengths of test bars presented across the blind spot with lengths of reference bars presented at the corresponding location in the fellow eye. Test bar lengths ranged from 7-14 deg. Reference bar lengths were in the range of +/- 3 deg of test bar length. From the observers' responses the perceived length of each bar at the blind spot was estimated. Estimates of the precision of length discrimination at the blind spot were also obtained. Our results were consistent with the associative explanation. In all seven observers, length distortions at the blind spot were smaller than 1 deg (< 20% of the vertical height of the blind spot) for all bar lengths tested. For bars that were presented across the blind spot, the precision with which observers could discriminate length was comparable to that of normal periphery (Weber fraction approximately 20%). Both the veridicality and precision of perceived length are preserved around the blind spot. PMID- 7786859 TI - Cephalometric analysis of changes produced by a modified Herbst appliance in the treatment of Class II division 1 malocclusion. AB - This study investigated treatment changes produced by the Herbst appliance in a sample of severe Class II division 1 cases, over a period of 8 months. The sample consisted of 16 girls, of whom eight were treated by the Herbst appliance, whilst eight served as controls. All cases were matched with respect to age, sex, skeletofacial morphology, and length of treatment/observation period. Twenty-two skeletal and 19 dental parameters were recorded on pre- and post-treatment cephalograms. The net treatment effect of Herbst therapy was evaluated, taking into account the growth that occurred in the control sample. The study revealed that during 8 months of Herbst therapy there was a significant increase in mandibular length, along with sagittal repositioning. The skeletal changes in the mandible were mainly responsible for overjet and molar relation correction. A slight, favourable forward rotation of the mandible was identified. Dentoalveolar features included flaring of lower incisors and distalization of upper molars. The appliance did not have any retrusive effect on the maxilla. The modified splint design differed from the original and was cemented rather than bonded. PMID- 7786860 TI - Consent and orthodontic treatment. PMID- 7786861 TI - Stability of the lower labial segment following orthodontic treatment--a comparison of treatment with Andresen and Begg appliances. AB - This retrospective cephalometric study of Class II division 1 malocclusions investigates the effects on the lower labial segment of two forms of orthodontic treatment. Non-extraction Andresen myofunctional therapy and first premolar extraction Begg treatment are compared to the lower incisor changes found in appropriate non-extraction and first premolar extraction control groups, which also presented with Class II division 1 malocclusions. Using four angular and two linear measurements, the lower labial segment was found to procline during Andresen therapy (1-2 degrees, 1-2 mm), and on withdrawal of the appliance it retroclined by about one-half of the in-treatment proclination (0.4-0.8 degrees, 0.1-0.5 mm). During extraction Begg mechanics, the lower incisors were found to retrocline (1.3-1.5 degrees, 0.4-0.9 mm), and they continued to retrocline following removal of the appliance (0.2-3.0 degrees, 0.8-1.1 mm). In general, the variables used to measure lower incisor position demonstrated only very small changes, and were near method error. The reliability of these changes are discussed. It is considered that the axial inclination of the lower incisor in relation to the mandibular plane is the most consistent and therefore still the most useful clinical measurement of lower incisor change available from cephalometric radiographs. PMID- 7786862 TI - Effects of cyclic stressing on attachment bond strength using glass ionomer cement and composite resin. AB - Bonded orthodontic brackets were subjected to cyclic loading in order to simulate the effect of occlusal forces. The subsequent effect on bond strength was determined. Stainless steel, mesh-based brackets were bonded to extracted teeth with either composite resin or glass ionomer cement. A jig was designed to subject each bracket to a preselected loading level and the 24-hour shear/peel bond strength of both stressed and unstressed brackets was subsequently measured. Cyclic loading brought about a comparative decrease in bond strength when using both types of material. The potential implications of selecting these different types of bonding material for clinical use are discussed. PMID- 7786863 TI - An investigation into the fluoride release of a variety of orthodontic bonding agents. AB - The purpose of this study was to compare the fluoride release from a variety of orthodontic bonding agents. Fluoride release into de-ionized water was measured over a 20-week period. Material based on the fluoride exchange resin was also tested in a saline solution. Fluoride release from a variety of orthodontic bonding agents was compared and the amount of release found to be highly variable. Glass ionomer-based materials showed substantially greater fluoride release when compared with resin-based materials. The presence of anions (Cl-) did not improve the release from fluoride exchange resin. Glass ionomer/resin hybrid material (Vitrabond) released the greatest amount of fluoride. PMID- 7786864 TI - Bond strengths of ceramic brackets using different bonding techniques. AB - A series of laboratory investigations was carried out to compare the shear-type bond strengths and site of bond failure of ceramic orthodontic brackets bonded to etched enamel. When light-cured composite resin was used as the luting agent, there was no reduction in bond strength when using 2.5 per cent nitric acid to etch the enamel, compared to 37 per cent phosphoric acid. The use of the two resin modified glass ionomer cements were found to give rise to significantly lower bond strengths than composite resin when used for placing ceramic brackets. Significantly less composite resin remained on the enamel surface following bracket removal in those samples etched with nitric acid. PMID- 7786866 TI - Financial consequences of reducing treatment availability in a publicly-funded orthodontic service. A decision analysis problem. AB - When a third party is responsible for funding a component of the health service, cost/benefit assessments become important. Such assessments become urgent when the budget is reduced. In this paper decision analysis has been applied to evaluate potential savings by reducing the proportion of children offered free orthodontic treatment through the National Health Service in Denmark. Data for the development of the decision tree was acquired using the Delphi technique. The results suggest that a reduction in the proportion of children offered early treatment might ultimately lead to an increased consumption of resources. Further investigation of the issue is needed before definitive recommendations can be made. PMID- 7786865 TI - The effect of artificial saliva on the frictional forces between orthodontic brackets and archwires. AB - The effect of artificial saliva on the static and kinetic frictional forces of stainless steel (Dentaurum) and polycrystalline ceramic (Transcend) brackets in combination with 0.018-inch round and 0.019 x 0.025-inch Edgewise archwire sizes and stainless steel, nickel-titanium and beta-titanium archwire materials, under a constant ligature force were investigated. In all cases, artificial saliva had the effect of increasing the frictional force when compared with the dry state. PMID- 7786867 TI - The Consultant Orthodontists Group survey of hospital waiting lists and treated cases. AB - A questionnaire sent to all U.K. hospital orthodontic consultants resulted in an 88 per cent response rate. The average waiting time for initial consultation was 31.6 weeks for routine cases and 3.6 weeks for urgent cases. The average waiting time for out patient treatment was 68.7 weeks for routine cases and 7.5 weeks for urgent cases. Nearly 33 per cent of hospitals used the Dental Health Component of the Index of Orthodontic Treatment need (IOTN) as a guide to placing patients on waiting lists. 'Urgency' and 'Complexity' were used more frequently than indices. Sixty-nine per cent of hospitals exclude some categories of malocclusion from treatment in their departments. A prospective survey reported on 2480 completed treatments over a six week period and there was an average discontinuation rate of 9.2 per cent of all cases finished during the period. Comparison of the completed and discontinued groups revealed few significant treatment-related factors. There was some evidence that the more senior and experienced the operator, the less the rate of discontinuation. A greater rate of discontinuation was seen in removable appliance cases when compared with fixed appliance cases. PMID- 7786869 TI - A sectional approach to the alignment of ectopic maxillary canines. AB - A sectional fixed appliance is described for the alignment of ectopic maxillary canines. This system has a number of advantages over conventionally employed mechanics. These include both good aesthetics and optimal tooth alignment. PMID- 7786868 TI - An evaluation of the views of general dental practitioners who have participated in an extended orthodontic training scheme. AB - A questionnaire was sent to 255 dental practitioners who had participated in an extended orthodontic training scheme, incorporating formal teaching and supervised clinical sessions over a period of not less than 24 months. The response of the practitioners was good; 78 per cent of the forms returned were suitable for analysis. Overall, the practitioners responded favourably to the schemes and felt that they had been of benefit to their clinical practice. The majority undertook more orthodontic treatment as a result and on average, fixed appliances were used in half of these treatments. PMID- 7786870 TI - Congenital absence of the atlas posterior arch. A case report. AB - A report of a healthy young adult woman with non-pathological congenital absence of the lateral and posterior parts of the atlas is presented. This occurred in association with a steep mandibular plane angle and an extremely obtuse gonial angle. Similar facial features are common in females with hypoplastic dorsal arches, and this case illustrates the intimate developmental association between the upper part of the cervical spine and the craniofacial complex. PMID- 7786871 TI - A new instrument for composite removal after debonding. PMID- 7786874 TI - Non-completion of active orthodontic treatment. PMID- 7786872 TI - Quality assurance in orthodontic radiography. AB - The implementation of a Quality Assurance (QA) programme in orthodontic radiography is designed to improve the quality of the resultant radiographs and to reduce the number of repeat exposures. This is particularly desirable in orthodontic practice where the majority of patients are young and therefore more at risk from the detrimental effects of X-rays. A programme is described and QA tests are given that may be applied in the surgery. Particular emphasis is placed on QA measures for extraoral radiography, since this is frequently undertaken in the treatment of the orthodontic patient. PMID- 7786873 TI - The thoughts of Chairman Bill: an interview with William Proffit. Interview by O. Keith. PMID- 7786875 TI - A comparative evaluation of Class II treatment strategies--Lysle Johnston at the Royal Berkshire Hospital. PMID- 7786876 TI - Dental hygienists in Australia and their employment in orthodontic practice. AB - Dental hygienists are the designated dental auxiliary of the future in Australia. This article explains how their duties came into existence and why their duties in orthodontic practice seem limited in some instances. Dental hygienists, a class of operating dental auxiliaries, work in Australian orthodontic practices, but their employment is not widespread. The ratio of hygienists to dentists is reported to be 1:40 in Australia and 1:10 in South Australia (Pash, personal communication). PMID- 7786877 TI - Placebo: a potent but misunderstood psychotrope. PMID- 7786878 TI - [Sleep, respiration and benzodiazepines: effects of benzodiazepines on nocturnal respiration]. PMID- 7786879 TI - Neuroprotective effect of selenium on iminodipropionitrile-induced toxicity. AB - The present investigation was undertaken to study the effect of selenium on experimental dyskinesia in rats. The movement disorders were produced in rats by intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100 mg/kg per day for 12 days. Selenious acid was administered daily 30 minutes before IDPN in the doses of 5 mumol/kg, 10 mumol/kg and 20 mumol/kg bodyweight in three different groups of rats. Animals were observed daily for any neurobehavioral changes including circling, backwalking, head weaving and twitching. Immediately after behavioral studies, blood and brain specimens were collected for analysis of thiobarbituric acid reactive substances (TBARS) to measure the extent of free radical production. Our results showed that concurrent use of selenium significantly inhibited IDPN-induced neurobehavioral changes in a dose-dependent manner. Treatment of rats with selenium also reduced the TBARS production in blood and different regions of brain. These findings suggest that selenium attenuates the IDPN-induced neurotoxicity by inhibiting lipid peroxidation. PMID- 7786880 TI - Fluoxetine in panic disorder: pharmacologic and tritiated platelet imipramine and paroxetine binding study. AB - Serotonergic implication in panic disorder has been demonstrated by the efficacy of serotonin reuptake blockers in treatment. Fluoxetine, a potent 5-HT reuptake blocker, has been suggested to have anti-panic efficacy. This open study examines 30 patients (eight males and 22 females) with an average age of 36.9 years, ranging from 18 to 62, who were treated for eight weeks with fluoxetine (mean dose 20 mg per day). All patients fulfilled DSM-III-R criteria of panic disorder with agoraphobia as determined in a SCID interview schedule. Out of 28 patients who started medication, 64% of the patients completed the clinical trial and 36% of the patients dropped out of treatment because of increased anxiety or a lack of efficacy. Thirty-two percent of the patients had zero panic attacks by week 3. By the end of eight weeks of treatment, 48% of the patients had zero panic attacks. There was a significant reduction in anxiety and phobic avoidance and panic attacks. Tritiated platelet imipramine and paroxetine bindings revealed significantly lower maximal binding for patients with panic disorder in comparison with controls. Paroxetine Bmax showed a trend to increase in the direction of control values by the end of the trial. PMID- 7786881 TI - Temperature gradient gel electrophoresis analysis of the beta-NGF gene in schizophrenia. AB - Methods for localizing functional polymorphisms in candidate genes are important for the elucidation of pathogenesis in complex diseases such as schizophrenia and manic depression. Temperature gradient gel electrophoresis (TGGE), a variant of denaturing gradient gel electrophoresis (DGGE), can detect single-base mutations in a specified region of double-stranded DNA. This technique has been evaluated for use with polymerase chain reaction (PCR)-generated DNA fragments containing either transitional (A to G) or transversional (T to A) mutations. Single-base mutations of both types are detectable in PCR fragments up to 500 bp long. This method was then used to examine the coding region of the beta-nerve growth factor (NGF) gene for polymorphisms in PCR-generated DNA fragments derived from lymphocyte DNA of subjects with schizophrenia and normal subjects. No single-base mutations in sequence coding for the mature beta-NGF peptide were found in any of the subjects who were examined. If DNA sequence information is available for PCR primer design, TGGE detection of DNA polymorphisms can be used to rapidly determine whether or not a defect in a gene of interest contributes to the pathophysiology of the illness. PMID- 7786882 TI - Chronic dopamine antagonism facilitates opiate-induced feeding. AB - Chronic interference with dopamine (DA) transmission has been found to facilitate opiate reward and opiate-induced behavioral activation derived from the nucleus accumbens. This study was aimed at determining the extent to which these effects are generalizable to opiate-induced feeding. Rats were tested for their feeding response to morphine following chronic interference with DAergic transmission with the long-acting neuroleptic, flupenthixol decanoate (FLU). It was found that FLU-treated animals showed an enhanced feeding response to morphine following three and four weeks of DA blockade, but not on weeks 1 and 2. Neither morphine treatment in FLU-control animals nor chronic FLU treatment alone produced any such time-dependent facilitation in feeding. The results indicate that the increased sensitivity to the rewarding effects of opiates following chronic DA blockade is generalizable to opiate-induced feeding. PMID- 7786883 TI - Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates. AB - Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5 HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5 HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5 HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5 HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors. PMID- 7786885 TI - Effect of blood sampling on apomorphine-induced penile tumescence in erectile impotence: a case report. AB - Apomorphine HCl (Apo) (0.5 mg sc), but not placebo, induced an erectile response (monitored with a mercury strain gauge) lasting 40 min in an impotent hyperprolactinemic patient. Serial blood sampling modified the 40 min erectile response. Prompt detumescence followed by complete or partial restoration of tumescence occurred each time blood was drawn. This observation points to the sensitivity of the Apo-erectile response to experimental procedures subjectively perceived as anxiogenic. PMID- 7786886 TI - An open-label study of famotidine as a treatment for schizophrenia. PMID- 7786887 TI - Optimization of epoxyeicosatrienoic acid syntheses to test their effects on cerebral blood flow in vivo. AB - Epoxyeicosatrienoic acids (EETs), normally present in brain and blood, appear to be released from atherosclerotic vessels in large amounts. Once intravascular, EETs can constrict renal arteries in vivo and dilate cerebral and coronary arteries in vitro. Whether EETs in blood will alter cerebral blood flow (CBF) in vivo is unknown. In the present study, the chemical synthesis of four EET regioisomers was optimized, and their identity and structural integrity established by chromatographic and mass spectral methods. The chemically labile EETs were converted to a sodium salt, complexed with albumin, and infused into anesthetized rats via the common carotid. The objective was to test whether sustained, high levels of intravascular EETs alter CBF. The CBF (cortical H2 clearance) was measured before and 30 min after the continuous infusion of 14,15- (n = 5), 11,12- (n = 5), 8,9- (n = 7) and 5,6-EET (unesterified or as the methyl ester, n = 5 for each). Neither the CBF nor the systemic blood pressure was affected by EETs. Because the infusions elevated the plasma concentrations of EETs about 700-fold above normal levels (1.0 nM), it is unlikely that EETs released from atherosclerotic vessels will alter CBF. PMID- 7786884 TI - The effect of adjunctive light therapy on ameliorating breakthrough depressive symptoms in adolescent-onset bipolar disorder. AB - Seven adolescents or young adults (aged 16 to 22 years) who met DSM-III-R criteria for bipolar disorder were treated for persistent depressive symptoms (greater than three weeks) with adjunctive light therapy (10,000 lux given twice per day). Patients were evaluated using the Beck Depression Inventory (BDI) and Symptoms Check List (SCL-58). Three patients showed a marked response of greater than 70% decrease of their baseline score. Two patients had a moderate decrease (40% to 74%) and two patients obtained mild to no response. There were no reported side-effects. Paired t-tests done on pre- and post-BDI scores (pre mean = 21.2 sd +/- 10.0; post mean = 11.1, sd +/- 8.8; paired t = 4.31; p > 0.0051) and pre- and post-SCL-58 scores above baseline of 58 (pre mean = 57.4, sd +/- 24.4; post mean = 28.7, sd +/- 18.6; paired t = 5.50; p > 0.0015) showed significant improvement. These preliminary results indicate that some bipolar adolescents with breakthrough depressive symptoms could benefit from light therapy as an adjunct to their continued thymoleptic treatment. PMID- 7786888 TI - The role of calcium influx in cellular proliferation induced by interaction of endogenous ganglioside GM1 with the B subunit of cholera toxin. AB - The B subunit of cholera toxin, which binds specifically to ganglioside GM1, is mitogenic for quiescent Swiss 3T3 fibroblasts. It was previously shown that the B subunit had no effect on cAMP, protein kinase C or phosphoinositide turnover, but did cause an increase in the influx of calcium from extracellular sources (Spiegel, S. and Panagiotopoulos, C. (1988) Exp. Cell Res. 177, 414-427). In contrast to the action of known growth factors, the B subunit induced significant DNA synthesis after only a 1-3 h treatment. We utilized this unique property to determine whether the increase in calcium influx plays a role in B subunit induced mitogenicity. Cells were briefly treated with the B subunit in the presence of calcium channel blockers, followed by removal of the blockers and further incubation in B subunit-free medium for the remaining time required to measure DNA synthesis. When 1 mM cobalt was only present during the first 3 h incubation. DNA synthesis induced by either the B subunit or fetal bovine serum was completely abolished. However, both nickel (1 mM) adn the L-type voltage gated calcium channel inhibitor nicardipin (10 microM) inhibited B subunit induced cell proliferation without abrogating the response to fetal bovine serum. Using a gel retardation assay, we found that the B subunit markedly stimulated specific DNA-binding activity of the transcription factor, activator protein-1 (AP-1), which functions as a major convergence point coupling early events induced by a variety of mitogens to long term growth responses. Presence of c-Fos protein in the AP-1 complex was demonstrated as a supershift band in the gel mobility assay using c-Fos polyclonal antibody. Cobalt, which markedly inhibited B subunit-induced DNA synthesis, also completely abolished AP-1 DNA-binding activity stimulated by the B subunit. In sharp contrast, cobalt had no effect on DNA-binding activity of AP-1 induced by the tumor promoter, 12-O tetradecanoylphorbol 13-acetate. Our results suggest that calcium influx is a key element for both DNA-binding activity of AP-1 and cell proliferation induced by binding of the B subunit of cholera toxin to cell surface ganglioside GM1. PMID- 7786889 TI - Phospholipid hydrolysis of mildly oxidized LDL reduces their cytotoxicity to cultured endothelial cells. Potential protective role against atherogenesis. AB - Oxidized low density lipoproteins (LDL) are cytotoxic to cultured endothelial cells and thereby are potentially involved in endothelial cell injury and atherogenesis. Oxidized phospholipids of oxLDL undergo spontaneous hydrolysis (PL hydrolysis) by LDL-associated phospholipase A2 (PLA2) activities. The present study aimed to investigate whether hydrolysis of oxidized phospholipids contained in mildly oxLDL could influence their cytotoxicity to cultured endothelial cells. PL-hydrolysis (spontaneous or mediated by exogenous PLA2) of mildly oxLDL elicited a significant reduction of their cytotoxicity to cultured endothelial cells. The reduced cytotoxicity of PL-hydrolysed oxLDL was not due to their reduced uptake by cells, but rather to their reduced content of oxidation products which are liberated by PL-hydrolysis and released (at least the more polar compounds) in the aqueous phase, as shown by ultrafiltration experiments. Oxidation products released in the aqueous phase were not or only slightly cytotoxic to endothelial cells, probably because a selective uptake of non oxidized fatty acids as shown by studies of uptake of oxidized and non oxidized [1-14C]linoleic acid. These data suggest that during PL-hydrolysis of mildly oxLDL, (i) oxidized phospholipids are hydrolysed; (ii) oxidation products liberated from oxLDL particles are released (at least in part) to the aqueous phase; (iii) the cytotoxicity of oxLDL to endothelial cells is reduced, probably because oxidized free fatty acids (released by PL-hydrolysis towards the aqueous phase) are not taken up by the cells. Finally, the possibility of a favourable role of PL-hydrolysis of oxLDL against atherogenesis is discussed. PMID- 7786890 TI - omega-Hydroxylation of docosahexaenoic acid or arachidonic acid in human colonic well differentiated adenocarcinoma homogenate. AB - Human colonic well differentiated adenocarcinoma homogenate was incubated with NADPH and docosahexaenoic acid (22:6(n-3)) or arachidonic acid (20:4(n-6)) as a substrate. On a selected ion monitoring chromatogram obtained with reversed phase high-performance liquid chromatography thermospray mass spectrometry, omega hydroxydocosahexaenoic acid (omega-HDHE) or omega-hydroxyeicosatetraenoic acid (omega-HETE) from an incubation mixture of the homogenate was detected in significant amount, compared to that from a colonic region remote from the carcinoma. In contrast, epoxydocosapentaenoic acids and the dihydroxy derivatives from 22:6(n-3) or epoxyeicosatrienoic acids and the dihydroxy derivatives from 20:4(n-6) were detected in low amounts, compared to that from a colonic region remote from the carcinoma. The results suggest that highly active NADPH-dependent omega-oxidations of polyunsaturated fatty acids occur in colonic adenocarcinoma homogenate. PMID- 7786891 TI - Characterization of specific subcellular 15-hydroxyeicosatetraenoic acid (15 HETE) binding sites on rat basophilic leukemia cells. AB - 15-Hydroxyeicosatetraenoic acid [15-(S)-HETE], a major arachidonic acid metabolite produced from the 15-lipoxygenase pathway, has been characterized as an antiinflammatory cellular mediator since it can inhibit the in vivo and in vitro formation of the proinflammatory leukotrienes via the 5-lipoxygenase pathway in various cells. 15-HETE has been confirmed to inhibit the 5 lipoxygenase in rat basophilic leukemia cell (RBL-1) homogenates with an I50 = 7.7 microM. The I50 of the 12-HETE isomer was 6 microM whereas prostaglandin F2 alpha was ineffective. In order to examine the mechanistic basis underlying the inhibitory action of 15-HETE, association assays of [3H]-15-HETE with RBL-1 subcellular fractions were carried out. The presence of the zwitterionic detergent CHAPS enhanced specific [3H]-15-HETE binding in the membrane fractions three-fold and specific 15-HETE binding was distributed among the nuclear (32%)-, granule (19%)-, plasma membrane (35%)-, and cytosol (14%)-enriched fractions. Studies using combined granule and plasma membrane enriched-, CHAPS treated fractions showed that [3H]-15-HETE binding was time-dependent, specific and reversible, sensitive to pertussis toxin treatment, and indicated a single class of binding sites with a Kd = 460 +/- 160 nM and Bmax = 5.0 +/- 1.1 nM. Competition experiments showed that the order of 15-HETE or analogs in inhibiting the binding of [3H]-15-HETE was: 15(S)-HETE > or = 12-(S)-HETE = 5-(S)-HETE > 15 (R)-HETE > arachidonic acid. Prostaglandin F2 alpha and lipoxin B4 were ineffective as competitors. The similar profiles of the binding assays and inhibition of the 5-lipoxygenase suggest that 15-HETE binding sites may mediate this inhibitory action of 15-HETE. PMID- 7786893 TI - Photoaffinity labeling of cottonseed microsomal N-acylphosphatidylethanolamine synthase protein with a substrate analogue, 12-[(4-azidosalicyl)amino]dodecanoic acid. AB - N-Acylphosphatidylethanolamine (NAPE), an unusual acylated derivative of phosphatidylethanolamine (PE), is synthesized from free fatty acids and PE in cotton seedlings (Chapman and Moore (1993) Plant Physiol. 102(3), 761-769). Here we use a photoreactive dodecanoic acid analogue, [12-(4 azidosalicy)amino]dodecanoic acid (ASD), and its 125I-labeled derivative to identify a protein subunit which corresponds to this cottonseed NAPE synthase activity. Dodecylmaltoside (DDM)-solubilized microsomal NAPE synthase enzyme was irreversibly and progressively inactivated by adding increasing concentrations of ASD and illuminating with UV254 light. Protection from this photoinactivation was afforded by the natural substrate, palmitic acid. In low light, microsomal NAPE synthase utilized ASD as a substrate to synthesize NAPE; palmitic acid competed for this activity. NAPE synthase activity was measured directly in gel slices following nondenaturing PAGE of DDM-solubilized microsomal membrane proteins. Two dimensional electrophoresis (nondenaturing PAGE, followed by SDS-PAGE) of photoaffinity-labeled, DDM-solubilized microsomal proteins revealed a 64 kDa polypeptide that was associated with the active NAPE synthase enzyme. Also, a 64 kDa protein was photoaffinity labeled in all NAPE synthase isozyme fractions isolated by preparative isoelectric focusing; photoaffinity labeling of this 64 kDa polypeptide was diminished in the presence of exogenously supplied palmitic acid. Collectively, our results demonstrate that ASD specifically interacts with NAPE synthase in a manner analogous to its fatty acid substrate and indicate that a 64 kDa polypeptide is a component of cottonseed microsomal NAPE synthase. ASD will be a useful molecular probe in future studies aimed at understanding the physiological role of this NAPE synthase enzyme in membranes of plant cells. PMID- 7786894 TI - Purification and characterization of two forms of cytochrome b5 from an arachidonic acid-producing fungus, Mortierella hygrophila. AB - Two forms of cytochrome b5 have been purified from the microsomes of an arachidonic acid-producing fungus, Mortierella hygrophila IFO 5941, after detergent solubilization. They have monomeric molecular masses of about 16 kDa and 19 kDa. Their absorption spectra are similar to those of mammalian cytochrome b5s. Their amino acid compositions show some similarity to those of mammalian cytochrome b5s, but the contents of some amino acids (glycine, alanine, aspartic acid + asparagine, glutamic acid + glutamine, arginine, proline, histidine, leucine and lysine) are unique to the cytochrome b5s of M. hygrophila. Some of their internal peptide sequences also show close homology with those of some mammals (approx. 65 to 67%), while some others show no or little homology. The addition of various acyl-CoAs to NADH-reduced microsomes caused an abrupt shiftdown of the steady state reduction level of cytochrome b5. This indicates the increased utilization of electrons for the desaturation process and may suggest that the cytochrome b5s of this fungus actually take part in its microsomal desaturation system for polyunsaturated fatty acid biosynthesis as electron carriers. PMID- 7786892 TI - Effect of Escherichia coli lipopolysaccharide on surfactant secretion in primary cultures of rat type II pneumocytes. AB - The purpose of this study is to evaluate the effect of the Escherichia coli lipopolysaccharide on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, in primary cultures of rat alveolar type II pneumocytes. Lipopolysaccharide stimulated phosphatidylcholine secretion in a time- and dose-dependent manner. At a concentration of 200 micrograms/ml, lipopolysaccharide stimulated the release of phosphatidylcholine 4-fold over the basal secretory rate, and the concentration producing half the maximal response was 20 micrograms/ml. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to that of the protein kinase C activator TPA, which is a potent stimulator of surfactant secretion. Lipopolysaccharide did not activate protein kinase C, which suggests that stimulation of phosphatidylcholine secretion by the endotoxin was through a mechanism independent of protein kinase C activation. PMID- 7786895 TI - Suppression of clofibrate-induction of peroxisomal and microsomal fatty acid oxidizing enzymes by growth hormone and thyroid hormone in primary cultures of rat hepatocytes. AB - Using primary cultures of rat hepatocytes on a matri-gel, effects of peroxisome proliferator and omega-hydroxydodecanoic acid on cellular levels of acyl-CoA oxidase and CYP4A have been studied to determine the hormonal influence in serum free media. Peroxisomal acyl-CoA oxidation, microsomal CYP4A content and laurate omega-hydroxylation were increased in rat hepatocytes by the addition of 100 microM clofibrate or Wy14,643 for two days. omega-Hydroxydodecanoic acid (100 microM) also increased peroxisomal acyl-CoA oxidation, but had no clear effect on microsomal CYP4A level and laurate omega-hydroxylation. CYP4A-mediated laurate omega-hydroxylation in hepatocytes was suppressed by the addition of pituitary growth hormone (0.05 mU/ml), but was not altered by the addition of triiodothyronine (30 nM). In contrast, clofibrate-mediated induction of acyl-CoA oxidase activity was decreased by the addition of either one of the hormones in hepatocytes. Suppression by those hormones was also observed with omega hydroxydodecanoic acid-mediated induction of acyl-CoA oxidase activity. These results indicate the possibility that GH and T3 exert the suppressive effects on peroxisomal acyl-CoA oxidation through plural mechanisms with and without the alteration of CYP4A levels in livers. PMID- 7786897 TI - Eicosapentaenoic acid causes transient accumulation of lipids in rat myocardium. AB - Rats were given eicosapentaenoic acid (EPA) or palmitic acid (PALM) up to 15 days, and control animals were given carboxymethylcellulose. All suspensions which were given by gastric intubation contained tocopherol. Heart triacylglycerols, heart cholesterol and heart phospholipids significantly increased after one day of EPA treatment, but they were normalized within 15 days. Both after 2 and 10 days of treatment with palmitic acid the heart triacylglycerols were significantly greater than control. The heart cholesterol and heart phospholipids were significantly greater than control after 10 days of treatment with palmitic acid. Total carnitine palmitoyltransferase (CPT) activity in heart was significantly greater in rats treated with EPA for 15 days compared to control, but treatment with palmitic acid had no effect. The fatty acyl-CoA oxidase activity was greater in rats treated with EPA for 15 days and palmitic acid for 10 days compared to control. The fractional volume of lipid droplets in myocardial cells was calculated from electronmicrographs and was 0.112 +/- 0.016% after 1 day of EPA treatment compared to 0.035 +/- 0.016% in the control group. After 5 and 15 days the fractional volume was the same as control. The fractional volume of lipid droplets in rats treated with palmitic acid for 10 days was 0.120 +/- 0.023%. Treatment with EPA caused an immediate accumulation of lipids and lipid droplets in the rat heart which after few days normalized in parallel with an increased activity of total CPT in the heart. PMID- 7786896 TI - Release of aldehydes from rat alveolar macrophages exposed in vitro to low concentrations of nitrogen dioxide. AB - This study demonstrated that aldehydes are released into the extracellular medium when alveolar macrophages (AM) are exposed to nitrogen dioxide (NO2) at concentrations that impair cell function but do not cause cell death. Butanal, glycolaldehyde, 4-hydroxynonenal, pentanal, pentenal, and hexanal were found. Dinitrophenylhydrazine (DNP) derivitization, thin layer chromatography, high performance liquid chromatography, and gas chromatography-mass spectrometry were used to identify the products. Some of the aldehydes have potential toxicity and may be responsible, in part, for altered AM function observed following NO2 exposure. PMID- 7786899 TI - 7 alpha-Hydroxylation of 25-hydroxycholesterol and 27-hydroxycholesterol in human fibroblasts. AB - The metabolism of 27-hydroxycholesterol and 25-hydroxycholesterol was studied in cultures of human diploid fibroblasts. Both steroids underwent 7 alpha hydroxylation with subsequent oxidation to 7 alpha-hydroxy-3-oxo-delta 4 steroids. A minor fraction of the 27-hydroxysteroids was oxidized to acids. Competition experiments indicated that both hydroxycholesterols were hydroxylated by the same enzyme, different from cholesterol 7 alpha-hydroxylase. 7 alpha,25 Dihydroxycholesterol suppressed the activity of HMG-CoA reductase at least as effectively as 25-hydroxycholesterol whereas 7 alpha,25-dihydroxy-4-cholesten-3 one was a less effective suppressor. The results suggest that cholesterol might be converted to 7 alpha-hydroxylated bile acid precursors in extrahepatic tissues in vivo and that the regulation of the activity of HMG-CoA reductase by oxysterols might be modulated by 7 alpha-hydroxylation and subsequent oxidation by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase. PMID- 7786898 TI - Effect of maternal ethanol consumption during pregnancy on the phospholipid molecular species composition of fetal guinea-pig brain, liver and plasma. AB - The effect of maternal ethanol consumption during pregnancy upon accumulation of docosahexaenoic acid (22:6(n - 3)) into developing brain phospholipids was determined in a guinea-pig model of fetal alcohol syndrome. Feeding adult guinea pigs 6 g/kg per day ethanol both before and throughout pregnancy was associated with decreased 22:6(n - 3) concentration in both fetal brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) at 40/68 days gestation and at term. Since adequate assimilation of 22:6(n - 3) into fetal brain is critical for optimal neuronal development, reduced accumulation of 22:6(n - 3) into phospholipids may be one important mechanism for ethanol-induced brain damage. Liver from ethanol exposed fetuses contained significantly lower concentrations of both PC and PE 22:6(n - 3)-containing molecular species. However, there was no difference in plasma PC polyunsaturated fatty acid content in ethanol-exposed fetuses compared with controls. One possible explanation for impaired 22:6(n - 3) accumulation into ethanol-exposed fetal brain phospholipids may be the result of the action of inappropriate mechanisms which counteract ethanol-induced increased membrane fluidity by reducing the polyunsaturated fatty acid content of brain phospholipids. PMID- 7786900 TI - In vitro determination by 1H-NMR studies that bile with shorter nucleation times contain cholesterol-enriched vesicles. AB - Although biliary vesicles are considered to be the primary source of cholesterol found in cholesterol gallstones, difficulties in quantitatively separating the different cholesterol transport modes in bile still remain. Proton nuclear magnetic resonance spectroscopy (1H-NMR) offers an alternative approach. Investigations were carried out on both model biles and human gallbladder bile samples: (i) to follow the effect of increasing sodium glycocholate concentrations on the 1H-NMR spectra of arachidonic acid rich-phospholipid, and cholesterol-lecithin vesicles, (ii) to compare the concentrations of total phospholipids in bile determined enzymatically with those obtained by integration of the phospholipid choline head group resonance peak, and (iii) to examine the relationship between biliary cholesterol nucleation time (NT) and the areas of the biliary lipid 1H-NMR peaks. It was found that the molecular motions of vesicle phospholipid, as determined by 1H-NMR, were restricted by saturation with cholesterol. In bile from patients with cholesterol gallstones, the reduced NMR fluidity of the phospholipid choline-head group indicated that the proportion of cholesterol-phospholipid vesicles containing more than 50% cholesterol, on a molar basis, was increased. The ratios of the N+(CH3)3 and = CH proton resonance peaks showed no overlap between samples with cholesterol gallstones and shorter NT and those with either no gallstones or pigment stones and longer NT. 1H-NMR spectroscopy indicates in a non-invasive manner those biles which are prone to cholesterol crystal formation. PMID- 7786901 TI - Phospholipid interactions affect substrate hydrolysis by bovine brain phospholipase A1. AB - The specificity of substrate hydrolysis by bovine brain phospholipase A1 (PLA1) was examined. In the presence of Mg2+, using pH values of 7 to 9, the purified enzyme deacylated 1-palmitoyl-2-[1-14C]arachidonoyl-phosphatidylethanolamine yielding 2-[1-14C]arachidonoyl-lysophosphatidylethanolamine at a rate of 70 mumol/min per mg. In the absence of Mg2+, however, the reaction rate slowed at pH values above 7.25. In contrast, brain PLA1 slowly (3.8 mumol/min per mg) hydrolyzed 1-palmitoyl-2-[1-14C]arachidonoyl-phosphatidylcholine (PAPC) unless phosphatidylserine (PS) was included. Maximal PAPC hydrolyzing activity required a PAPC/PS molar ratio of 2.5:1, Mg2+, and a pH value of 8.5-9.5. Replacing PS with phosphatidylethanolamine (PE) or phosphatidic acid (PA), but not phosphatidylinositol (PI), produced a similar effect. Moreover, hydrolysis of either arachidonoyl-substituted or dipalmitoyl-substituted PC at pH 7.5 was enhanced by increasing the mol fraction of PE. Brain PLA1 also hydrolyzed 1 stearoyl-[1-14C]arachidonoyl-PI with high velocity, but only if the substrate was dispersed in PE vesicles. In contrast, the velocity of PS, 1-palmitoyl-lyso-PC or diacylglycerol hydrolysis was low and unaffected by PE. In summary, PLA1 hydrolyzed PE with high velocity and specificity, whereas a high rate of PC or PI hydrolysis was observed only if PS, PE, or PA was present. In addition, PLA1 activity was greatly influenced by pH and Mg2+, implying that the substrate conformation is important to the catalytic efficiency of PLA1. Finally, the high rate of PE, PC or PI hydrolysis suggests PLA1 significantly contributes to the turnover of these phospholipids in the brain. PMID- 7786902 TI - Biliary lipid output by isolated perfused rat livers in response to cholyl lysylfluorescein. AB - The biliary output of bile acids and lipids is tightly coupled. The ability of the natural bile acid glycocholate to trigger biliary lipid secretion was compared with that of the fluorescent bile acid analogue cholyl-lysylfluorescein (cholyl-lys-F). When administered as a 5 min pulse of 2.5 mumol/min to bile acid depleted rat livers perfused under recycling conditions, glycocholate produced well-defined peaks of phospholipid and cholesterol output, and of bile flow, which were coincident with the peak of bile acid output. Although cholyl-lys-F did trigger biliary lipid secretion, its time course of appearance was delayed and well-defined peaks of output were not observed. However, the increased biliary output of phospholipid and cholesterol was coincident with that of bile acids and, as judged by phospholipid/bile acid and cholesterol/bile acid ratios, cholyl-lys-F was as effective as glycocholate in triggering biliary lipid output. When administered to livers perfused under single pass conditions, perfusate to bile transfer of glycocholate was > 85% at infusion rates of up to 5 mumol/min whereas transfer of cholyl-lys-F showed saturation at infusion rates of > 0.2 mumol/min; the time course of biliary output of both bile acids was similar. Thus, under recycling conditions, cholyl-lys-F not taken up during first pass will be continually represented for transfer to bile, explaining why bile acid and lipid output did not occur as well-defined peaks. PMID- 7786903 TI - Rate of release and retentivity of prostaglandin E1 in lipid emulsion. AB - The rates of release of prostaglandin E1 (PGE1) from lipid particles into aqueous solution were obtained by the dialysis method, for parenteral lipid emulsion (Lipo-PGE1) diluted 10-times with buffered solutions of various pH. The findings, which were the rates of release of PGE1, were used to calculate the amount of PGE1 distributed in lipid particles when Lipo-PGE1, diluted 100-times with various pH levels of the buffered solution, was administered by intravenous drip infusion. More than 90% of PGE1 was retained in the lipid particles and intravenously infused when transfusion fluid pH was less than 5.5 and 2 ml of Lipo-PGE1 and 198 ml of transfusion fluid had been mixed and were administered over 2 h. Results from simulation showed that half of the PGE1 was retained in lipid particles and was infused, if Lipo-PGE1 was diluted 100-times with pH 8 transfusion fluid. Though PGE1 was sparingly soluble in an aqueous solution, these findings demonstrated that a significant amount of PGE1 was retained in lipid particles. Thus, this dosage form is expected to be highly effective for a drug delivery of PGE1 in clinical treatment. PMID- 7786905 TI - Lipase from Chromobacterium viscosum: biochemical characterization indicating homology to the lipase from Pseudomonas glumae. AB - Previous purification of a commercial lipolytic preparation from Chromobacterium viscosum using gel filtration chromatography yielded two enzymatically active fractions, named lipases A and B. Characterization of these fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that lipase A consisted of a high molecular weight aggregate of lipase protein with lipopolysaccharides. This complex could be dissociated by treatment with EDTA Tris buffer containing the non-ionic detergent n-octyl-beta-D-glucopyranoside and subsequent isoelectric focusing in an agarose gel containing the same detergent. Both lipases A and B revealed a major peak corresponding to an isoelectric point of 7.1. SDS-PAGE analysis of lipases A and B after purification by gel filtration or by IEF revealed one major protein band of M(r) of 33 K. Determination of N terminal amino acid sequences confirmed that both fractions A and B contained the same lipase protein. Furthermore, the N-terminal amino acid sequence of the C. viscosum lipase was identical to the one of Pseudomonas glumae lipase. PMID- 7786904 TI - Species-specific polymorphism in the promoter of the apolipoprotein A-I gene: restoration of human transcriptional efficiency by substitution at positions 189, -144 and -48 bp. AB - Previous studies indicate that species-specific differences in apolipoprotein A-I (apo A-I) expression could be largely explained by cis-acting factors located within or near the 5' flanking region (-231 to +223 bp, where +1 is the start site of transcription). In the present studies, we have localized 7 sites within the (-231 to -15 bp) region of the African green monkey apo A-I gene that differ from the human apo A-I gene 5' flanking region. To identify which of the 7 polymorphic sites were essential for the species-specific differences in apo A-I gene expression, mutated promoter constructs were transfected into HepG2 cells and reporter gene expression was measured. Each of the 7 sites within a defined 5' flanking region of the human gene was individually mutated to the African green nucleotide sequence found at that position. Three of the sites (-189, -144 and -48) were found to raise the human apo A-I promoter activity to approx. 60 65% of the African green promoter. While double mutations (-144/-48 bp and -189/ 144 bp), restored the human apo A-I promoter activity to 100% of that found with the African green monkey promoter. Additional studies revealed similar DNA: protein interactions with DNA probes from either human or African green monkey and HepG2 cell nuclear extract. In conclusion, these studies demonstrate that double and triple nucleotide substitutions within the human apo A-I promoter are sufficient to restore gene expression in HepG2 cells to levels seen with the African green monkey promoter. These data suggest that sites -189, -144 and -48 bp are involved in significantly altering the binding affinity of a nuclear factor determining the species-specific level of apo A-I gene transcription. PMID- 7786906 TI - A set of male monozygotic triplets with schizophrenic psychoses: nature or nurture? AB - A set of schizophrenic male monozygotic triplets is described. At age 20 years, within 8 months the three men independently developed acute fulminant schizophrenic disorders (DSM-III-R) with auditory hallucinations, bizarre delusions, and thought disturbances. There were also great similarities between the triplets with regard to the chronic intermittent course of the disorder, impairment of social adjustment, and loss of working ability. The psychoses responded rapidly to conventional neuroleptic treatment. Neuropsychological assessment demonstrated similar marked reductions of attentional, mnestic, and executive functions. Magnetic resonance imaging (MRI) showed similar borderline ventricular enlargement and widened subarachnoid spaces over frontoparietal and basal regions as well as around the pituitary gland (empty sella). All the boys also had a right-sided hearing defect with a marked reduction of the ossicular bones on the right side. Possible clues as to etiological mechanisms were the lack of reported family history for the disorder and a possible influenza infection in the mother during the first trimester. It is suggested that a DNA aberration being present or occurring at conception initiated a precise time programmed series of events that produced the very similar schizophrenic phenotypes. Such an aberration might have been induced by an external agent, occurred spontaneously, or been inherited by a recessive mechanism. It seems possible that the psychoses, the reductions of neuropsychological functions, the morphological MRI changes, and the right-sided ossicular reductions may all be related to such a DNA alteration. PMID- 7786908 TI - Factors affecting public attitudes towards mental health care. AB - This study presents a telephone survey of 501 randomly sampled residents of the Grand Duchy of Luxembourg older than 15 years of age. The interviewees were questioned on their attitudes and judgements towards mental health care in Luxembourg. The implementation of a community-based mental-health-services delivery system in Luxembourg is in its initial stages. Being the smallest member of the European Community Luxembourg offers the opportunity to analyze a whole catchment area in transition marked off clearly by national borders. As a general rule the people of Luxembourg are undecided when it comes to mental health care. Almost half of the sample answered "don't know" when asked about the quality of several sectors of mental health care, excluding inpatient care. The factors that had a significant influence on the attitude of the people of Luxembourg regarding mental health care were nationality, age, class and personal contact with mentally ill persons, with a tendency of worse judgements in younger age groups and in members of upper social classes. We fitted multivariate models including these variables. The results of our study point to entrenched prejudice. The findings suggest, however, that attitudes are changeable by direct or indirect contact with mentally ill persons. Possible strategies that could change public attitudes towards mental health care in a mental health care system that is in transition are discussed. PMID- 7786907 TI - Intelligence and temperament as protective factors for mental health. A cross sectional and prospective epidemiological study. AB - The Sjobring system of personality dimensions measuring intellectual capacity, activity, impulsivity and sociability was used to study possible "salutogenic" (i.e. causes of health) effects. The study comprised 590 subjects investigated in 1947, 1957, 1972 and 1988-1989 in the Lundby project, an epidemiological study in Sweden. Psychiatric diagnoses were made in 1947, 1957 and 1972. Mental health was estimated in 1988-1989 using the concept "love well, work well, play well and expect well". The Sjobring dimensions were clinically assessed in 1972. Both in the concurrent study in 1972 and in the prospective study in 1988-1989 "super capacity" (high intellectual function), "super validity" (high activity level) and "super solidity" (low impulsivity) were statistically associated with lower frequencies of certain psychiatric diagnoses and a higher frequency of positive mental health. These variables are proposed to increase coping capacity, and therefore increase stress resilience. PMID- 7786909 TI - Nonlinear analysis of sleep EEG in depression: calculation of the largest lyapunov exponent. AB - Conventional sleep analysis according to Rechtschaffen and Kales (1968) has provided meaningful contributions to the understanding of disturbed sleep architecture in depression. However, there is no characteristic alteration of the sleep cycle, which could serve as a highly specific feature for depressive illness. Therefore, we started to investigate nonlinear properties of sleep electroencephalographic (EEG) data in order to elucidate functional alterations other than those obtained from classical sleep analysis. The application of methods from nonlinear dynamical system theory to EEG data has led to the assumption that the EEG can be treated as a deterministic chaotic process. Chaotic systems are characterized by a so-called sensitive dependence on initial conditions. This property can be quantified by calculating the system's Lyapunov exponents, which measure the exponential separation of nearby initial states in phase space. For 15 depressive inpatients (major depressive episodes according to DSM-III-R criteria) and 13 healthy controls, matched in gender, age, and education, we computed the principal Lyapunov exponents L1 of EEG segments corresponding to sleep stages, I, II, III, IV, and rapid eye movement (REM), according to Rechtschaffen and Kales, for the lead positions CZ and PZ. We found statistically significant decreased values of L1 during sleep stage IV in depressives compared with a healthy control group. PMID- 7786910 TI - Psychiatric morbidity among repatriated Greek migrants in a rural area. AB - This paper reports on psychiatric case identification by the application of the Structured Clinical Interview for DSM-III-R (SCID) in a sample of 198 Greek migrants repatriated from western europe in a northwestern province of Greece. The current (1 month) prevalence of psychiatric morbidity, based on the total number of diagnosed cases, was found to be 43.4%. Lifetime prevalence of psychiatric disorders was found to be higher (49.4%). The majority of the sample were diagnosed as suffering from anxiety disorders and dysthymia. Psychiatric disorders were found to be more prevalent among middle-aged respondents. Duration of stay in the foreign country was a factor correlated with psychiatric morbidity. Of short-term migrants 54% were found to suffer from specific nosological entities, whereas 32% of long-term migrants were diagnosed as cases. The results are discussed within the framework of the existing sociocultural context of emigration and repatriation. PMID- 7786911 TI - Dopamine D2 receptor gene polymorphisms in Scandinavian chronic alcoholics: a reappraisal. PMID- 7786912 TI - Comment to "Dopamine D2 receptor gene polymorphisms in Scandinavian chronic alcoholics: a reappraisal". PMID- 7786914 TI - Radionuclide ventriculography in dynamic cardiomyoplasty. AB - Dynamic cardiomyoplasty improves ventricular function by increasing pump function and by limiting cardiac dilatation. The aim of this study was to assess long-term myocardial performance by radionuclide ventriculography on dilated cardiomyopathy patients subjected to cardiomyoplasty. Thirteen survivors were included. Radionuclide ventriculography was performed one week before surgery and one year later. Five patients were also studied two years following surgery. The left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and ventricular amplitude ratio (VAR) to assess mitral regurgitation were measured. Every case after one year showed a non-significant increase in LVEF. However, the decrease in EDV and in VAR was significant (p < 0.01). No significant difference in these values was found after two years. We conclude that the effects of cardiomyoplasty -reduction of cardiac dilatation, wall stress and mitral regurgitation--are more evident during the first year after surgery. Thereafter, a certain stabilization is observed. PMID- 7786913 TI - Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration. AB - The nocturnal myoclonus syndrome (NMS) consists of stereotyped, repetitive jerks of the lower limbs that occur during sleep or wakefulness. NMS is often related with restless-legs syndrome (RLS) and can cause severe sleep disturbances and daytime sleepiness. The efficacy of dopamine agonists in the treatment points to a dopaminergic dysfunction in NMS. We investigated the central dopamine D2 receptor occupancy with [123I] labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2 pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) ([123I]IBZM) and single photon emission tomography (SPET) in 20 patients with NMS and in 10 healthy controls. In most of the patients with NMS there was a lower [123I]IBZM binding in the striatal structures compared to controls. The results indicate that NMS is related to a decrease of central D2 receptor occupancy. PMID- 7786915 TI - Rest distribution of 99mTc-MIBI in patients with coronary artery disease assessed by SPECT: comparison with the distribution of [18F]FDG assessed by PET. AB - The distribution of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), assessed by single photon emission computed tomography (SPECT) was compared to the distribution of 2-[18F]-2-deoxy-D-glucose ([18F]FDG) assessed with positron emission tomography (PET) under fasting conditions, in 21 patients with coronary artery disease (CAD) and severe left ventricular dysfunction in order to evaluate the potential usefulness of SPECT/99mTc-MIBI for the identification of viable myocardium. Stress and rest SPECT/99mTc-MIBI studies were scored based on the percent of 99mTc-MIBI uptake defined by semi-quantitative circumferential-profile analyses. PET metabolic studies with [18F]FDG under fasting conditions, were adopted as a standard of viability. The results of the comparison of 99mTc-MIBI and [18F]FDG distribution showed that among the segments with stress hypoperfusion, [18F]FDG uptake was present in 95% of the segments that had > 40% of the peak tracer uptake at the rest SPECT/99mTc-MIBI study. [18F]FDG uptake was also present, however, in 25% of the segments that had < 40% uptake at the rest SPECT/99mTc-MIBI scintigraphy. We conclude that in patients with CAD the pattern of 99mTc-MIBI distribution appears to underestimate the extent of viable myocardium but only in those regions that are very severely hypoperfused. PMID- 7786916 TI - Locating neuroblastoma in the opsoclonus-myoclonus syndrome. AB - We examined the role of various medical imaging modalities, particularly metaiodobenzylguanidine (MIBG) scintigraphy in the investigation of patients presenting with the opsoclonus-myoclonus syndrome (OMS) who may harbor neuroblastomas. A retrospective analysis was therefore performed of all patients presenting with OMS in a 5 1/2 year period. Between December, 1988 and May, 1994, all 13 patients (mean age 15.2 months, range 3 days-30 months) presenting with OMS were extensively studied. A wide range of medical imaging modalities including CT, MRI and [131I] or [123I]-metaiodobenzylguanidine (MIBG) scintigraphy (total of 21 scans) were examined as a means of detecting a structural brain lesion or locating a neuroblastoma, a tumor generally found in less than half of patients with OMS. As anticipated a minority of patients (4) were eventually found to harbor neuroblastomas. In these four cases, two tumors were revealed on preoperative MIBG scintigraphy, one gave a false negative study and one tumor was not studied preoperatively. Each patient was also subjected to extensive radiological investigations in addition to MIBG scintigraphy, many of which were repetitive, redundant or had low clinical yield. The relative merits of the various procedures are compared, and an algorithm incorporating MIBG scintigraphy and limited central nervous system and abdominal anatomical modalities for the investigation of opsoclonus-myoclonus is suggested. PMID- 7786917 TI - Determination of glomerular filtration rate with 99mTc-DTPA in clinical practice. AB - In order to assess the practical reliability of glomerular filtration rate (GFR) determination with 99mTc-DTPA and plasma sampling, the authors compared the results obtained with 51Cr-EDTA and 99mTc-DTPA in 50 patients using five easily applied methods (two double-plasma-sample methods and three single-plasma-sample methods), and two kits with different compositions. It was observed that: 1) there is no difference between the results obtained with the two different kits. 2) Compared with 51Cr-EDTA the 99mTc-DTPA overestimates the result by about 2 mL/min: precision is slightly lower with 99mTc-DTPA than with 51Cr-EDTA but is sufficient for practical use. 3) The method recommended by the authors on the basis of this experience is the Russell's method with two samples. 4) The simplified methods with one sample give comparable results to the Russell's method for GFR levels between 50 and 115 mL/min, while the results are unsatisfactory below 50 mL/min. 5) Among the single-sample methods, the authors suggest that of Christensen and Groth. 6) A preliminary estimate of GFR (from the serum creatinine level, for instance) is useful for the choice between double plasma-sample methods and simplified methods. In conclusion, the authors consider that the estimation of GFR with 99mTc-DTPA can be performed efficiently in clinical practice even when operating in absolutely routine conditions. PMID- 7786918 TI - Different tracers and stressors in patients with coronary artery disease: how to standardize clinical questions and nuclear cardiology answers. AB - The recent introduction of new tracers and stressors has increased the number of combinations of techniques that can be used for the diagnostic and prognostic stratification of patients with coronary artery disease. However, these new techniques still need to be standardized for clinical use. Thallium-201 scintigraphy is at present the most common method to assess transient ischemia and viability in patients. Dynamic exercise and dipyridamole show similar incidence of major cardiac complications and their use can be considered sufficiently safe. Further experimental and multicenter clinical studies are needed for 99mTc-Sestamibi and 99mTc-Teboroxime and for new stressors such as adenosine and dobutamine. PMID- 7786919 TI - The future of SPECT radioisotopes: technetium-99m or iodine-123? PMID- 7786920 TI - 111In-octreotide uptake in granulomatous and tumor lesions in a patient with small-cell lung cancer. AB - A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer. PMID- 7786921 TI - A bioimaging integration system implemented for neurological applications. AB - A system aimed at the management and fusion of multimodal biomedical images, including X-ray computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, has been implemented for neurological applications. This bioimaging integration system (BIS) consists of a network for image transmission from acquisition machines to dedicated image processing workstations, a software library for image standardization, and an image registration technique to project multimodal volumetric images into a common reference space. The registration procedure was evaluated in MRI/PET correlation studies, in which misalignment errors of 2.6 mm in the xy transaxial plane and 3.4 mm along the z axis were found. BIS has been validated for the anatomical-functional correlation analysis of MRI and PET images in neurological research protocols and clinical studies. PMID- 7786922 TI - Micronuclei and 3AB-index in patients receiving iodine-131 therapy. AB - In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for cancer, the micronucleus (MN) frequency observed in peripheral blood lymphocytes (MN-test on binucleated cells) had a weighted mean of 0.044 +/- 0.006 (SEM), which was significantly different (p < 0.001) from that observed in 93 healthy individuals (0.025 +/- 0.001). The MN frequency (F(MN)) of the patients correlated fairly well (R = 0.736) with the modified activity (Amod) calculated by the following equation: [formula: see text] where Ai is the 131I activity on a determined day, e the logarithm base, di the number of days that have passed between the determined day and the day when the blood was drawn, and k is a day coefficient, defined in this context as the "daily attenuation factor". The use of the value of 0.0003 for k allowed the following equation to be obtained: F(MN) = 7.9 x 10(-5) (+/- 1.4 x 10(-5)).Amod + 0.014 (R = 0.736) The MN frequency was used to estimate, by our DOSIME program, the dose (Gy) received at the individual level in the 131I treatment. In these subjects the calculated dose was well correlated with Amod by the relationship: DBio = 0.0009 (+/- 0.0002).Amod + 0.0675 (R = 0.755) 3-aminobenzamide (3AB), an inhibitor of the poly(ADP-ribose)polymerase enzyme involved in DNA repair, induced and increase in X-ray cytogenetic damage (MN yields), evaluated at the individual level using the 3AB-index (I-3AB). The index was obtained from the MN-yield count after x irradiation with (MN + 3AB) and without (MN - 3AB) 3AB, using the following formula: I = 1-(MN - 3AB/MN + 3AB).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786923 TI - Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats. AB - In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6 biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues. PMID- 7786924 TI - Reliability of psychophysiological responding as a function of trait anxiety. AB - This study examined the temporal stability of three psychophysiological responses (frontal electromyographic activity, hand surface temperature, and heart rate) recorded over four sessions (days 1, 2, 8, and 28) on 34 subjects, 17 with high Spielberger Trait Anxiety Inventory scores and 17 with low scores. Each session consisted of a 20-minute adaptation period, a baseline condition, and two stressors (one cognitive, the other physical). Two forms of reliability coefficients were employed, intraclass correlations and Pearson Product Moment; the two types of reliability coefficients arrived at the same conclusions. Results indicated that reliability coefficients for the two anxiety groups did not differ on frontal EMG or heart rate responses; however, hand surface temperature responding was considerably less reliable for high anxious individuals than low anxious individuals. Reliability coefficients on absolute scores were, for the most part, reliable. Treating the responses as relative measures (percent change from baseline or simple change scores from baseline) produced smaller and less reliable coefficients. Magnitudes of the three physiological responses did not significantly differ as a function of high or low trait anxiety. Findings are discussed in terms of their clinical, as well as basic psychophysiological, importance. PMID- 7786925 TI - Assessment of lumbar EMG during static and dynamic activity in pain-free normals: implications for muscle scanning protocols. AB - The purpose of this study was to provide a thorough description of lumbar surface integrated electromyography (EMG) in pain-free normals during a standardized assessment protocol of static isometric and unresisted dynamic tasks. It has been proposed that in pain-free normals, symmetrical tasks that bend the trunk forward or extend the trunk backward produce symmetrical paraspinal EMG activity, and asymmetrical tasks that rotate or laterally bend the trunk produce asymmetrical paraspinal EMG activity. In addition, it has been observed that lumbar EMG assessment during static tasks has been more consistent than tasks involving dynamic activities. Twenty-eight pain-free normals were assessed during symmetrical and asymmetrical tasks in both static and dynamic activities in a counterbalanced manner. The assessment of paraspinal EMG patterns was conducted while subjects were secured in a triaxial dynamometer, which provided standardization of body position and concurrent measurement of torque, range of motion, and velocity. The results provided experimental evidence for the above stated propositions. An implication derived from this research is that clinicians may be better served utilizing local norms when using EMG for classification purposes. PMID- 7786926 TI - Electromyographic recordings of paraspinal muscles: variations related to subcutaneous tissue thickness. AB - The aim of this study was to assess the effect on EMG amplitude measures of variations in the thickness of underlying tissue between surface electrodes and the active muscle. 20 normal subjects with different amounts of subcutaneous tissue performed comparable constant force contractions for a 45-second period, during which paraspinal EMG recordings were taken. Three measures of subcutaneous tissue thickness were obtained from each subject: Body Mass Index, total body fat as calculated by Durnin's formula, and skinfold thickness at the recording sites. The results show that (i) the greater the thickness of subcutaneous tissue between the surface recording site and the contracting muscles, the lower the recorded electromyographic activity, and that (ii) up to 81.2% of the variance in the EMG measures can be explained by variation in the amount of subcutaneous tissue. These findings support the view that the absolute level of surface recorded EMG cannot simply be taken at face value. The amplitude of the signal will be affected by, for example, the amount of body fat. PMID- 7786927 TI - The relationship of expectancies to outcome in stress management treatment of essential hypertension: results from the Joint USSR-USA Behavioral Hypertension Project. AB - Outcome expectancy and efficacy expectancy measures were made during the course of a cross-cultural comparison of thermal biofeedback and autogenic training as treatments for mild essential hypertension. There were no differences between groups at either pre- or posttreatment, and expectancy measures were not related to initial success or failure at the completion of treatment. However, both outcome and efficacy expectations were related to relapse over the three months immediately following the completion of treatment. Treatment failures had lower ratings for both outcome and efficacy expectations at the posttreatment assessment in comparison to treatment successes. Implications of these results are discussed. PMID- 7786929 TI - Evaluation of the effectiveness of EEG neurofeedback training for ADHD in a clinical setting as measured by changes in T.O.V.A. scores, behavioral ratings, and WISC-R performance. AB - A study with three component parts was performed to assess the effectiveness of neurofeedback treatment for Attention Deficit/Hyperactivity Disorder (ADHD). The subject pool consisted of 23 children and adolescents ranging in age from 8 to 19 years with a mean of 11.4 years who participated in a 2- to 3-month summer program of intensive neurofeedback training. Feedback was contingent on the production of 16-20 hertz (beta) activity in the absence of 4-8 hertz (theta) activity. Posttraining changes in EEG activity, T.O.V.A. performance, (ADDES) behavior ratings, and WISC-R performance were assessed. Part I indicated that subjects who successfully decreased theta activity showed significant improvement in T.O.V.A. performance; Part II revealed significant improvement in parent ratings following neurofeedback training; and Part III indicated significant increases in WISC-R scores following neurofeedback training. This study is significant in that it examines the effects of neurofeedback training on both objective and subjective measures under relatively controlled conditions. Our findings corroborate and extend previous research, indicating that neurofeedback training can be an appropriate and efficacious treatment for children with ADHD. PMID- 7786928 TI - Differences in baseline EEG measures for ADD and normally achieving preadolescent males. AB - This study was designed as a replication of previous studies describing dynamic EEG differences between behaviorally dissimilar groups. This study is intended as a reference point from which other researchers can continue to establish the EEG correlates of "on-task" behavior. Eight Attention Deficit Disordered (ADD) children and eight Normally Achieving Controls (NAC) were assessed using dynamic EEG measures. Results are reported for the tasks of baseline (eyes open), reading, and drawing as recorded from FZ, CZ, PZ, C3, and C4. Significant amplitude differences between the groups were demonstrated in the theta band (4-8 hertz) during all tasks and for all sites. Amplitude differences in the beta band (12-20 hertz) were negligible. Differences between groups expressed as a ratio of theta/beta revealed significant differences mainly in the parietal region for on task conditions. These results are discussed in relation to EEG neuro-feedback training paradigms and the importance of establishing normative "on-task" EEG values. PMID- 7786930 TI - [XII Congress of the Spanish Society of Parenteral and Enteral Nutrition. Madrid, 3-6 May 1995. Abstracts]. PMID- 7786933 TI - Perceptions of the contemporary status of smoking-control strategies. PMID- 7786931 TI - Towards a population-based screening program for cervical cancer. PMID- 7786932 TI - The health of Australians of non-English-speaking background: key concerns. PMID- 7786935 TI - Smoking in New Zealand: a census investigation. AB - New Zealand may well be unique in that in the 1976 and the 1981 Censuses of Population and Dwellings, persons over the age of 15 were asked about their cigarette smoking habits. The data are available on the basis of age and ethnicity, enabling an examination of the prevalence of ever-smoking by a cohort born some 80 years before the censuses were taken, at the end of the last century. Thus the effect of ever-smoking on mortality can be calculated. Ever regularly smoking reduced the life expectation of males by 11.7 years and females by 15.6 years. The corresponding reductions for Maori were 19.3 years and 23.8 years. The effect of smoking on health has been of epidemic proportions, notably for the Maori. PMID- 7786934 TI - Increase in the self-reported prevalence of asthma and hay fever in adults over the last generation: a matched parent-offspring study. AB - The study compared current measures on a population-based cohort of adults with past measures on their parents to determine whether the prevalence of self reported asthma and hay fever in adults increased between 1968 and the early 1990s. In 1968, 8585 cohort members (99 per cent of eligible Tasmanian 7-year-old school children born in 1961), 16,273 (95 per cent) of their parents (mean age 35 years) and 20,937 siblings completed a questionnaire about asthma and hay fever. In 1991-1993, 1494 members (75 per cent) of a stratified random sample of the cohort (aged 29 to 32 years), 75 per cent resident in Tasmania, were surveyed again. In 1968, the proportion of parents who reported having ever had asthma or attacks of wheezing like asthma was 10.9 per cent, independent of age and sex. In 1991-1993, the estimated adult prevalence of having ever suffered from attacks of asthma or wheezy breathing was 23.2 per cent. The proportion reporting at least one asthma attack within the previous 10 years, 5 years, 2 years, 12 months and 6 months was 17.6 per cent, 16.1 per cent, 14.5 per cent, 13.3 per cent and 10.3 per cent, respectively. For hay fever, the adult prevalence was 19.2 per cent in 1968, and 41.3 per cent in 1991-1993. The self-reported lifetime prevalence of asthma and hay fever among adults in the 1961 birth cohort of Tasmanians was twice as high in 1991-1993 as in their parents 25 years earlier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7786936 TI - Quitting smoking: estimation by meta-analysis of the rate of unaided smoking cessation. AB - The rates (after 12 months' follow-up) of unassisted smoking cessation reported in the literature have varied from 13.8 per cent to 8.5 per cent. A meta-analysis was conducted of the abstinence rates observed in 14 samples of smokers who presented at primary health settings and received either no intervention aimed at smoking or usual care (which involved no deliberate intervention for smoking cessation). The estimated rate of stopping smoking without intervention, over an average 10-month period, was 7.33 per cent. This rate is consistent with others reported in the literature when motivation to quit is taken into account. The estimate provides a baseline to judge the effects of smoking-cessation interventions. PMID- 7786937 TI - Predictors of unprotected male-to-male anal intercourse with casual partners in a national sample. AB - The focus of the paper is the predictors of unprotected anal intercourse with casual partners among a national Australian sample of homosexually active men. We interviewed by telephone 2583 homosexually active men (sex with a man within the last five years) about their sexual practice, type of sexual partners, human immunodeficiency virus (HIV) test status, attachment to the gay community, knowledge of HIV and acquired immune deficiency syndrome (AIDS) and a range of demographic variables. Logistic regression analyses were used to distinguish men who practised unprotected anal intercourse with casual partners from those who practised safe sex with casual partners. Men who practised unprotected anal intercourse with casual partners were less likely to have a regular male sexual partner than men who practised safe sex with their casual partners. They were less likely to be tertiary educated, more likely to be employed in trade and manual occupations and to live in Tasmania and the Northern Territory. They were less likely to be culturally or politically attached to the gay community. Knowledge of HIV/AIDS also distinguished the men: men with an accurate knowledge of HIV transmission were less likely to engage in unprotected anal intercourse with their casual partners. Several other variables, including age and HIV test status, did not distinguish those who practised safe sex with casual partners from those who practised unprotected anal intercourse with casual partners. PMID- 7786938 TI - An improved aetiologic fraction for alcohol-caused mortality. AB - A method is proposed for estimation of alcohol-caused mortality in which the aetiologic fraction of deaths is derived from an exposure contrast between the 'unsafe' drinker and 'safe' drinker; not between the drinker and the nondrinker. The method is consistent with the objectives of public health intervention in the alcohol education field. The 'safe' drinker is the reference exposure category and aetiologic fractions are obtained for the single categories of a multiple level exposure scale, using separate relative risks for the 'unsafe' drinker and the nondrinker. Preliminary application of the method to Australian data yields an estimate of the number of deaths caused by misuse of alcohol that is larger than those obtained under the old conceptual model. Thus, the public health importance of unsafe alcohol consumption has been underrepresented. PMID- 7786939 TI - A controlled trial of educational visiting to improve benzodiazepine prescribing in general practice. AB - A randomised controlled trial studied the effect of an educational visit on benzodiazepine prescribing. An approximately representative sample of 286 general practitioners was allocated to an intervention or a control group. Rates of benzodiazepine prescriptions were derived from two comprehensive self-report surveys seven months apart. Two months after the first survey the intervention group received an educational visit and supporting material from a doctor or pharmacist, ostensibly unconnected with the surveys. The overall benzodiazepine prescribing rate fell by 23.7 per cent from the first to the second surveys, from 4.93 to 3.76 prescriptions per 100 encounters (P < 0.001). Anxiety and insomnia diagnosis rates also declined from 4.68 to 3.76 per 100 encounters (19.7 per cent). After adjusting for confounders, there was a differential downward trend in prescriptions per diagnosis of insomnia but not to a statistical level. The same was true of initial prescriptions per insomnia diagnosis. In a subsidiary analysis selecting only new insomnia diagnoses, the intervention had a strong effect in reducing initial prescriptions (odds ratio 0.18, 95 per cent confidence interval 0.04 to 0.73). No effect was seen on prescribing for anxiety diagnoses. Educational practice visiting for benzodiazepine prescribing in anxiety, as we conducted it, is not justified in an unselected population of general practitioners. Specific education on prescribing for insomnia is probably useful. Our interpretation of the reduction in benzodiazepine prescribing is that probably there was an effect from self-monitoring alone which overwhelmed a main analysis intervention effect. Retrospective diagnosis may also have obscured a real intervention effect. PMID- 7786940 TI - Injury from assault in New Zealand: an increasing public health problem. AB - Injury purposely inflicted by other persons is a significant public health problem accounting for approximately 4 per cent of all injury hospitalisations in New Zealand. National injury morbidity data for the years 1979-1988 were examined. These data were used to identify the characteristics of victims of assault who were hospitalised, the nature of the injuries they sustained, and the circumstances in which the injuries were inflicted. The incidence of hospitalisations in 1988 was 73.7 per 100,000 persons per year. A significant increase in the rate of hospitalisations over the decade 1979-1988 was identified. The rates for males were higher than those for females, with males 20 24 years of age most at risk. Maori had higher rates than non-Maori. Fights or brawls were the leading cause of hospitalisation. The most common place of occurrence was private homes, followed by streets and highways, and licensed premises. The findings with regard to age, sex, employment status and use of weapons were consistent with earlier studies. A higher proportion of incidents occurring in the home was attributed to differences in selection of cases between studies. An indication of underreporting by women was attributed to concealment of intentionality, possible owing to fear of reprisal. Standard hospital reporting procedures were proposed as a means of improving identification. PMID- 7786941 TI - Critical path analysis for the management of fractured neck of femur. AB - The aim of this study was to determine the effect of a critical path analysis, used as a management tool, on the efficiency of clinical service delivery for patients with a fractured neck of femur. It is a before-and-after study of the medical records of all patients admitted between October 1992 and October 1993 with a primary diagnosis of fractured neck of femur, but excluding patients under 50 years old and those with multiple fractures or metastatic disease. Patients fell into two groups: those admitted in the six months before the introduction of a clinical management program based on a critical path analysis, and those admitted after the introduction of the program in April 1993 (88 program cases and 90 nonprogram cases). A medical records administrator blinded to the program category of the patients independently coded diagnostic data, while other data were abstracted from the clinical notes. The length of stay for a fractured neck of femur declined from a mean of 19.3 days to a mean of 11.0 days (P < 0.0001). The outcome measures were: the distance walked just before discharge from hospital, the discharge destination, and unplanned readmission. These did not change significantly, and the wound infection rate declined during the period of the intervention. The implementation of a clinical management pathway based on a critical path analysis dramatically reduced the length of stay for patients admitted with a fractured neck of femur while maintaining quality of outcomes. Critical path analysis is a useful management tool to improve the efficiency of certain clinical services. PMID- 7786942 TI - The SF-36 in an Australian sample: validating a new, generic health status measure. AB - The SF-36 is a self-reported, 36-item, generic measure of health status that has been validated for adult age groups in the United States, the United Kingdom and in some non-English-speaking countries. The Australian Bureau of Statistics used it in the 1995 National Health Survey and it has been used in health status measurement, in monitoring health outcomes and in clinical trials. The validity of the SF-36 was examined in the National Centre for Epidemiology and Population Health Record Linkage Study using a sample of 555 respondents to the National Heart Foundation Risk Factor Prevalence Survey in 1989; they were followed up in 1992. Items chosen for the scale had been used in health status assessment and had stood the test of time. The health concepts measured demonstrated good internal consistency. The eight scales of the SF-36 formed factors as predicted in the general health dimensions of physical and mental health. The component scales of the SF-36 demonstrated good discrimination between people with and without health conditions, including those with medical and those with psychiatric types of conditions. Although the SF-36 was a valid measure of general health status among Australian respondents, further work is needed to establish clinical validity and to produce population norms for Australia. Use of the SF-36 will allow Australian and international comparison of health status from the point of view of the users of health services. PMID- 7786943 TI - Cervical screening in general practice. AB - This study examined the effect of three interventions for encouraging women to have a Pap smear in a general practice: tagging the medical record to remind the doctor to offer a Pap smear, sending an invitation to make an appointment for a Pap smear, and sending an invitation with an appointment to attend for a Pap smear at a special screening clinic staffed by women. The study took place in a university general practice at Lockridge, near Perth. A computerised practice age sex register provided 2139 women in the age range 36 to 69 inclusive. Of these, 757 were eligible for inclusion in the study and were allocated randomly to one of three intervention groups or a control group. In total, 177 women had a Pap smear during the study. Significantly more Pap smears were taken for the appointment-letter and letter-only groups than the control group (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.34 to 3.57, and OR 1.67, CI 1.01 to 2.77 respectively), but there was no significant difference between the tagged-notes and the control groups. Women who attended the screening clinic rated the experience positively. Attendance, however, was inadequate for the clinic's viability in a private practice. PMID- 7786944 TI - A prospective cohort study investigating psychosocial predictors of attendance at a mobile breast screening service. AB - This study aimed to examine whether knowledge, attitudes and concerns predicted attendance at the mobile Breast X-Ray Programme in Sydney. A cohort study design was used, whereby women were surveyed prior to the implementation of the program, and two years later records were checked to determine whether they had attended for screening. Telephone interviews were sought with randomly selected women aged 45 to 70 years living in the central Sydney area (the screening van's catchment area). A total of 285 women was surveyed (response rate: 50 per cent). Of these, 86 (30 per cent) subsequently attended at the mobile van and 199 did not. Attendance did not appear to be related to any of the following factors: knowledge; attitudes; prior experience; perceived susceptibility and morbid concern in relation to breast cancer; the amount of information about screening mammography to which a woman had been exposed. The results are interpreted in light of methodological considerations plus findings from our other research. PMID- 7786946 TI - Psychological impairment following motor vehicle accidents. AB - This study investigated the rate of psychological impairment and stressful life events in survivors of motor vehicle accidents. Fifty-six patients who had been hospitalised because of motor-vehicle-accident-related injuries were reviewed twelve months after the accident. In this sample, 41 per cent of patients reported significant levels of psychological impairment. Patients reporting psychological disturbance were characterised by having more pain, unemployment, substance abuse, avoidance of road transport and compensation claims. Only 44 per cent of patients reporting significant psychological impairment had sought professional help for their conditions. Psychological dysfunction following motor vehicle accidents appears to be a common occurrence, and education of medical personnel and survivors is required to enhance identification and management of this problem. PMID- 7786945 TI - Aboriginal wellbeing and liquor licensing legislation in Western Australia. AB - This paper is based on the results of a project undertaken as the basis for a submission to the committee established to review the Western Australian Liquor Licensing Act 1988. It reports on key issues relating to liquor licensing, as identified by members of regional Aboriginal organisations. Among these issues are the promotion of alcohol consumption and misuse, discriminatory practices by licensees and the police and the need for greater community involvement in liquor licensing decisions. To address these issues, members of the participating organisations proposed: inclusion of a harm-minimisation objective in the Act, education and training programs for the public, licensees and the police, and industry funding for harm-minimisation programs. PMID- 7786947 TI - Soil lead levels in parks and playgrounds: an environmental risk assessment in Newcastle. AB - In June 1993 the National Health and Medical Research Council set a national goal for blood lead of below 10 micrograms/dl. There is a need to know if the lead contamination of the urban environment is so high as to put community health at risk. Decisions, including whether soil should be removed and replaced, will have to be made. During the second half of 1993, an environmental assessment of lead contamination of soil within the City of Newcastle was conducted. Samples, 108 from surface soil and 10 from subsurface soil, were taken from public parks and playgrounds in the city area and analysed for lead content. The proportion within and the proportion above the guidelines for soil contamination were reported. Lead concentrations ranged from 25 to 2400 parts per million (ppm); 21 per cent of samples had concentrations higher than the 300 ppm action level, and the geometric mean was 134 ppm. Both the range and the average lead levels were typically no more than, or were even less than, soil lead levels documented for other cities in Australia, the United States and United Kingdom. Although each sampling site was noted, it was not our intention to focus in on individual sites. Indeed, to draw health-risk implications from any one result may be misleading and inaccurate. The results indicated moderate lead contamination of soil that could be controlled by regular top-dressing of soils, the use of bark chip on playground surfaces and by government initiatives aimed at lowering lead levels in petrol. PMID- 7786948 TI - Information for family carers: does it help? AB - Family carers in Victoria were identified through a statewide telephone survey in 1993. A total of 976 carers was interviewed and a random sample of approximately one in 10 (n = 103) were offered the Carer Support Kit leaflet. The leaflet details the components of the Carer Support Kit (a Federal Government initiative developed in 1992-93) and informs carers how to apply for it through the Victorian Carers' Association. Approximately three-quarters of these carers accepted the offer, and around a third subsequently applied for the kit. Carers who applied for the kit reported significantly more overload and lower life satisfaction than those who did not apply. Only two-thirds of those mailed the kit (just 23 per cent of the eligible study sample) went on to use it. Those who had not used it reported significantly more negative emotions and health problems than those who used it, suggesting that stress and crises could preclude utilisation of the information. A brief evaluation of the components of the kit is presented; however, findings need to be treated with caution in view of the small sample size. PMID- 7786949 TI - Ethnic health workers in primary health care. AB - Ethnic health workers were employed to increase the access of communities of non English-speaking background to health services, but their role has remained unclear in a national health system that has been criticised for being slow to respond to the needs of these communities. Interviews and a questionnaire were used to survey a convenience sample of 40 South Australian ethnic health workers, how they should perform their roles and their ability to fulfil them. Interviews with 11 staff from the New South Wales Ethnic Health Worker Program then provided a broader perspective to the South Australian findings. High-priority roles were to provide help to solve immediate health problems. Roles included providing access as well as services. There were pressures on ethnic health workers to become service providers: clients from non-English-speaking backgrounds expected assistance with a wide range of problems, and mainstream staff lacked competence in meeting these needs. Ethnic health workers' involvement in needs assessment and health agency change was limited by these pressures, by ethnic health workers' separation from the work of mainstream staff and because systematic planning of services to non-English-speaking communities was lacking. The appropriate role for an ethnic health worker is as an access provider, with a greater emphasis on needs assessment and agency change. Agencies need to develop culturally appropriate service plans and training so that ethnic health workers and mainstream staff are better able to work together. PMID- 7786950 TI - Community nutrition education for people with coronary heart disease--who attends? AB - A qualitative food-frequency questionnaire was administered by mail to a representative sample of 137 people previously diagnosed with possible or definite myocardial infarct. Seventy-eight percent of subjects returned a completed questionnaire and were subsequently invited to attend local tastings of foods with the National Heart Foundation Tick of Approval. These tastings were organised and promoted with the active involvement of the local branch of the Australian Cardiac Association. The purpose of this study was to measure voluntary participation by people with coronary heart disease in community nutrition education and to identify any self-selection bias with respect to eating habits among the participants. A dietary risk score, which was the proportion of all food choices that were high in fat, was calculated from the data. Eighteen per cent of subjects who answered also participated in the food tastings; there was a statistically significant association between membership of the Australian Cardiac Association and being a participant. Participants had a significantly lower risk score (P < 0.01) after adjustment for age, sex and membership of the association. The results suggest that voluntary participation by people with heart disease in community nutrition education is low and that there is a self-selection bias, with those at highest dietary risk being least likely to attend. The use of existing community networks to recruit participants is also discussed. PMID- 7786951 TI - Notifying women of the results of their cervical smear tests by mail: does it result in a decreased loss to follow-up of abnormal smears? AB - We undertook a prospective randomised intervention study of the proportions of women with abnormal cytology results who were lost to follow-up in 42 general practices in urban and rural Queensland over 26 weeks. Practices in the intervention group were provided with a redesigned cervical smear request form that allowed patients to provide an address for direct notification from the laboratory by mail. Satisfaction questionnaires sent to the general practitioners in the intervention group showed that most made at least some use of direct notification, and most felt it was worthwhile. For women with an initial result of cervical intraepithelial neoplasia (CIN), there was a loss to follow-up of 23 per cent (95 per cent confidence interval (CI) 11 to 39) among the control group compared to none in the intervention group (upper CI 7 per cent), a highly significant difference (P < 0.001). Mailing cervical screening results to women may reduce the loss to follow-up of those with CIN findings. PMID- 7786952 TI - Cars, boats, dogs ... why not guns? The case for national gun registration in Australia. PMID- 7786953 TI - Public health advocacy in the Northern Territory. PMID- 7786954 TI - Clozapine: the Yin and Yang of seizures and psychosis. PMID- 7786955 TI - Clozapine and seizures. AB - Epileptiform EEG changes, myoclonus, and seizures are reported in some patients treated with clozapine. Although these are undesirable side effects, the excitation of specific neuronal networks by clozapine and other neuroleptics may be important for the therapeutic effect of this class of agents. In these experiments, intraperitoneal clozapine 2-16 mg/kg produced dose-related myoclonic jerks in partially restrained rats. Paroxysmal slow waves and spike activity were recorded from implanted electrodes in amygdala, hippocampus, and cortex following higher doses of clozapine, but the EEG abnormalities were not correlated with the myoclonic jerks. Single doses of chlorpromazine (8 and 16 mg/kg) rarely produced myoclonic jerks but provoked generalized tonic seizures in two animals preceded by multiple myoclonic jerks in one. Myoclonus and seizures reflect increased excitability of the central nervous system. It is possible that clozapine and other neuroleptics exert a therapeutic effect by increasing excitability in critical subcortical areas of the brain. PMID- 7786957 TI - Platelet serotonin markers and depressive symptomatology. AB - Dysfunction of brain serotonergic symptoms may be a factor in the mood and behavioral disturbances associated with depression. Platelet serotonin measures represent indirect but easily obtainable indices of brain serotonin function. To examine the specificity of relationships between cognitive and vegetative symptom groupings and platelet serotonin measures, we assessed 35 depressed outpatients using the Hamilton Rating Scale for Depression and collected platelets after a minimum 3-week drug-free period. Platelets were also collected from 14 controls. The results showed that depressed patients had lower platelet serotonin (5-HT) uptake site density values than controls and that 5-HT uptake site density values were inversely correlated with the severity of cognitive symptoms of depression. Platelet 5-HT2 receptor density values were higher in depressed patients than controls, and there was a trend toward a direct correlation between the cognitive symptoms of depression and 5-HT2 receptor density values. Neither platelet measure showed any relationship with the severity of the vegetative symptoms of depression. PMID- 7786956 TI - Estrogen augments serotonergic activity in postmenopausal women. AB - To investigate the influence of estrogen replacement on serotonergic activity in postmenopausal women, the serotonin agonist meta-chlorophenylpiperazine (m-CPP) (0.5 mg/kg) was given orally to 18 normal postmenopausal women, 11 of whom were also tested following 30 days' treatment with estrogen transdermal patches (estraderm 0.1 mg). Fifteen normal, healthy women of reproductive status served as a control group. Cortisol and prolactin responses to m-CPP were measured. Without estrogen, the prolactin and cortisol responses of postmenopausal women to m-CPP were blunted compared to those of reproductive women. Estrogen replacement increased the hormonal responses. It is suggested that decreased serotonergic activity in postmenopausal women might contribute to their vulnerability to affective disorders. Estrogen replacement therapy might decrease this vulnerability and might add to the efficacy of serotonergic antidepressants when warranted. PMID- 7786958 TI - Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients. AB - This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls. The time course of diurnal heart rate also differed in acutely depressed patients from controls: acutely depressed patients started higher and converged by midday to normal levels. These diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression. PMID- 7786959 TI - The relationship between tiredness prior to sleep deprivation and the antidepressant response to sleep deprivation in depression. AB - Recently it was hypothesized that the antidepressant response to total sleep deprivation (SD) results from a disinhibition process induced by the increase of tiredness in the course of SD. In the present study, the role of tiredness in the antidepressant response to SD is further investigated. Seventy-two depressed patients scored subjective tiredness and depressed mood three times daily (in the morning, afternoon, and evening) on the days preceding and following SD. It was found that averaged tiredness on the day prior to SD was related to the SD response, when the severity of depression prior to SD had been held statistically constant. Also, when both severity of depression and diurnal variation of mood prior to SD were partialed out, tiredness showed a positive correlation with the SD response: patients who reported a relatively low degree of tiredness on the day preceding SD improved by SD. This result suggests that tiredness has an influence on SD effects, and that this influence is independent from that of the severity of depression. The findings are in accordance with current ideas on the role of tiredness as a mediating factor in the induction of the therapeutic effects of SD. PMID- 7786960 TI - A placebo-controlled trial of L-365,260, a CCKB antagonist, in panic disorder. AB - The functional role of cholecystokinin in the central nervous system is unknown. The tetra peptide CCK-4 was previously observed to induce panic attacks in a majority of normal volunteers and patients with panic disorder. Furthermore, it had been demonstrated that pretreatment with 10-50 mg of L-365,260, a selective CCKB antagonist, blocked CCK-4 induced panic in patients with panic disorder. Therefore, the present multicenter, placebo-controlled, double-blind trial was designed to investigate the efficacy of L-365,260, a CCKB antagonist, in patients with panic disorder with or without agoraphobia. Following a 1-week, single-blind placebo period, 88 patients were randomized to double-blind treatment in which they received either L-365,260, 30 mg qid, or placebo for 6 weeks. At the dose tested, there were no clinically significant differences between L-365,260 and placebo in global improvement ratings, Hamilton anxiety rating scale scores, panic attack frequency, panic attack intensity, or disability measures. The possible reasons for lack of effect with L-365,260 are discussed. PMID- 7786961 TI - Sensory cortical processing and the biological basis of personality. AB - Action-oriented personality traits such as sensation seeking, extraversion, and impulsivity have been related to a pronounced amplitude increase of auditory evoked scalp potentials with increasing stimulus intensity. Dipole source analysis represents a crucial methodological progress in this context, because overlapping subcomponents of the scalp potentials can be separated and can be related to their generating cortical structures. In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex. These results support the concept that the serotonergic brain system, which is supposed to modulate sensory processing in primary auditory cortices, is an important factor underlying individual differences in sensation seeking. PMID- 7786962 TI - Anxiolytic effects of chlordiazepoxide blocked by injection of GABAA and benzodiazepine receptor antagonists in the region of the anterior basolateral amygdala of rats. AB - The amygdala is a structure that is often implicated in the regulation of anxiety responses. Many studies have shown that injection of benzodiazepines into the amygdala produces an anxiolytic effect. The present study was undertaken to determine whether the anxiolytic effect of administration of systemic benzodiazepine (chlordiazepoxide) might be blocked by local injection of a benzodiazepine receptor antagonist (flumazenil) or GABAA receptor antagonist (bicuculline methiodide; BMI) into the region of the anterior basolateral amygdala (BLA) of rats using an ethologically based test of anxiety, the social interaction test. Injection of flumazenil or BMI into the BLA of rats was found to reverse the anxiolytic effects of peripherally administered chlordiazepoxide. These results suggest a major role for the BLA in mediating the anxiolytic effects of benzodiazepines. PMID- 7786963 TI - Bipolar affective disorder associated with beta-thalassemia minor. AB - A family suggesting cosegregation of beta-thalassemia minor and bipolar affective disorder was reported. The monogenic hereditary anemia was surveyed over three generations in this family, and three patients with the beta-thalassemia and the bipolar affective disorder were observed over two generations. The localization of a gene responsible for bipolar affective disorder was discussed on the basis of previous reports. PMID- 7786964 TI - CSF isatin is elevated in bulimia nervosa. PMID- 7786965 TI - No association of a tyrosine hydroxylase gene tetranucleotide repeat polymorphism in autism, Tourette syndrome, or ADHD. PMID- 7786966 TI - Parallel development of dopamine metabolism tolerance in the rat prefrontal cortex, caudate-putamen, and amygdala following haloperidol decanoate administration. PMID- 7786967 TI - Lateralized attentional abnormality in schizophrenia is correlated with severity of symptoms. PMID- 7786968 TI - The Office of Research Integrity Biannual Report 1991-1992. PMID- 7786970 TI - [Clinical usefulness of questionnaires in primary care]. PMID- 7786972 TI - [Characteristics of AIDS cases detected at a prison in Barcelona (1991-1993)]. AB - OBJECTIVE: To describe the cases of AIDS detected in a Barcelona prison. DESIGN: A prospective study. SETTING: A penitentiary for men in Barcelona. PATIENTS: All those inmates who had AIDS or were diagnosed with the illness during their stay in prison during the 36 months between 1/1/1991 and 31/12/93. RESULTS: 220 cases of AIDS (91.7% PVDA), 60% of which were diagnosed in prison. The PVDA were younger (p < 0.0001). There were a greater number of Spaniards among the UDVP (p < 0.01) and among those with tattoos (p < 0.001). The first manifestation of the disease in 53% of the cases was extrapulmonary Tuberculosis. CONCLUSIONS: Prisons are key places in the prevention and monitoring of HIV infection. The use of care programmes, including maintenance programmes using Methadone, for drug-dependent patients are recommended. The continuation of programmes tracking Tuberculosis, the main illness related to HIV infection in prison, is also recommended. PMID- 7786969 TI - Society of Biological Psychiatry 50th annual convention. Miami, Florida, May 17 21, 1995. Abstracts. PMID- 7786973 TI - [Is it possible to improve psychiatric care through the referral process?]. AB - OBJECTIVE: To evaluate the quality of referral from Primary Care to Mental Health and its relationship to the illness referred. DESIGN: A descriptive retrospective study over 4 years on the quality of the process. SETTING: Mental Health Centre II in the Autonomous Community of Murcia. PATIENTS: 209 patients referred by three Primary Care teams. MEASUREMENTS AND MAIN RESULTS: 91.4% of patients (C.I. 95%: 100%, 81.1%) were accepted with a referral report. 97.9% (C.I. 95%: 100%, 87.8%) presented a reason for psychiatric consultation. The report included the clinical history of the illness in 58.1% of cases (C.I. 95%: 70.3%, 45.9%); a diagnostic opinion was given in 79.6% (C.I. 95%: 91.1%, 68%); and 37.2% (C.I. 95%: 49.3%, 25%) were referred with a request for a specific consultation. 68.4% of the referrals (C.I. 95%: 81.8%, 54.9%) coincided with the Mental Health diagnosis. It was observed that among the most commonly referred pathologies: anxiety disorders (31.6%), affective (28.8%), personality (7.7%), psychotic (5.3%), and adaptive disorders (5.3%); diagnoses were commonly made for affective or anxiety disorders (p < 0.0001); the specific cause of referral of anxiety disorders was recorded (p < 0.01); and in cases of psychotic and personality disorders, the diagnoses did not coincide (p < 0.001). CONCLUSIONS: Referral to Mental Health can be improved, fundamentally by sending a report which includes the clinical history and the reason for referral. It is common to express a diagnostic opinion on affective and anxiety disorders, to note a specific reason for referral in the case of anxiety disorders and not to specify personality and psychotic disorders. PMID- 7786971 TI - [Family medicine tutors: attitudes and activities of tutoring]. AB - OBJECTIVE: To discover the attitude of tutors to tutoring and describe how they apply the teaching programme during the period interns spend at the Health Centre. DESIGN: Crossover study. Stratified random sampling by Teaching Units. SETTING: Primary Care Centres with teaching accreditation. PARTICIPANTS: 258 tutors from the state-wide Teaching Programme. MEASUREMENTS AND MAIN RESULTS: Tutors' attitudes and the activities undertaken with the interns were studied by means of a self-filled questionnaire. The attitudes scale revealed a good attitude toward tutoring. Above all ability to motivate (73%) was required of the good tutor. Shared quotas was the commonest model of tutoring (85%). Clinical care was the activity the tutors developed best (70%), with the doctor-patient relationship in second place (46%). The majority discussed the Clinical History with their intern (75%). Few supervised the carrying out of procedures (36%). 68% of interns performed at least one piece of research, although tutors thought they should do more investigative work (41%). During the three intern years, the relationship was hardly ever maintained (13%). CONCLUSIONS: Tutors' attitude to tutoring is adequate. There is agreement with the basic features of the Programme, which is best developed in the area of care. The general model is that of a shared quota. Teaching must be improved in the non-care aspects, with specific training being made available to tutors. PMID- 7786974 TI - [Relaxation therapy in patients with anxiety and somatoform disorders in primary care]. AB - OBJECTIVE: To study the effect of relaxation therapy on the symptomology of patients with anxiety and somatoform disorders. DESIGN: An experimental prospective study, controlled through random assignation, using evaluation scales. SETTING: Mn. Jaume Soler Health Centre, Cornella (Barcelona). PATIENTS: 31 patients (8 men and 23 women), diagnosed with anxiety or previously untreated somatoform disorders, for whom combined anti-depressive and relaxation therapy over a 5-month period was established. The results were compared with those of a control group (n = 17) with identical diagnoses, which only received antidepressive medication. MEASUREMENTS AND MAIN RESULTS: The STAI tests and two pain scales were administered at 0, 15, 30, 45, 60 and 150 days and the HRS and SCL-90-R at 0 and 150 days. The possible impact of the psychiatric diagnosis, age, gender, married status, existence of concomitant physical illness, SRE, present employment status and the presence of children or not were all considered. The results pointed to a significant improvement over the period in the analogue-visual scale of pain (p = .009) and in the HRS (p = .046) for the group comprised of those complying with the relaxation therapy independently of the psychiatric diagnosis. CONCLUSIONS: The benefit of relaxation in anxious and somatoform patients, when pain--and not anxiety--is the principal symptom, was confirmed. Depression improved when antidepressants were administered simultaneously, whereas anxiety varied little, at least during the time the trial lasted. PMID- 7786975 TI - [Evaluation of the surveillance system of chlorination of public water supply in the province of Albacete]. AB - OBJECTIVE: The aim was to study the reliability of the available data, stemming from the concordance between two different observers' measurement of the level of free residual chlorine. DESIGN: An observational, crossover study, using measurements of the level of free residual chlorine repeated on the same day by two different observers. SETTING: Health Area of Albacete. PATIENTS AND OTHER PARTICIPANTS: 176 double measurements of chlorine, carried out during the study period in 69 networks distributing different waters. MEASUREMENTS AND MAIN RESULTS: Concordance between observers on the absence or presence of chlorination was low (I.Kappa = 0.261), showing a bias in favour of the presence of chlorination in the measurements made by local technicians (McNemar p < 0.01). Applying a logistic regression model, it was observed that the risk of disagreement was as much as 8.5 times greater when chlorine measurement required the local technician to travel. CONCLUSIONS: We concluded that the data available was of questionable value and that it would be useful to put forward some new proposals to improve the supervision of the network. PMID- 7786977 TI - [Something more about adverse reactions to medications]. AB - OBJECTIVE: To describe adverse drug effects (ADE) and their frequency in primary care patients. DESIGN: Descriptive and longitudinal study during 1 year (1990). SETTING: Urban Health Center. Primary Care. Madrid (Spain). PATIENTS AND OTHER PARTICIPANTS: 15,483 persons, nine general practitioner and one pharmacist. INTERVENTIONS: Doctors were invited to register any adverse drug effects they had notice in their patients. Doctors registered information and gave notice to the pharmacist about medicines, dosage and period of administration, clinical manifestations, and improving or not if drug was withdrawal. MEASUREMENTS AND MAIN RESULTS: 326 adverse drugs effects were notified, 30.9 ADE per thousand attended patients. 117 principles actives were involved, and 415 clinical manifestations were registered. The more affected patients were women (2/1). The age groups with higher ADE relative frequencies were children under one year and older people. CONCLUSIONS: The absolute frequency of medicines involved in ADE are different to relative frequencies when ADE per thousand prescription units are used. Some of the ADE notified were not referred before in the bibliography, so primary care is a good place to research on pharmacosurveillance. PMID- 7786976 TI - [Tuberculous infection in the province of Las Palmas (1990-1993)]. AB - OBJECTIVE: The objective of this study was the study of the parameters of tubercular infection (prevalence and RAI) arising from tuberculin surveys of the school-age population. DESIGN: A descriptive study of a crossover type, looking at each school year. SETTING: The surveys were carried out among the entire school population (n = 10,711) of all the public and private schools in Las Palmas. PARTICIPANTS: The population under study was a representative sample of first-year EGB students (age 6-7) of the 1990-91 (n = 1,951), 1991-92 (n = 2,505) and 1992-93 (n = 2,208) school intakes. There was a "no authorisations" index of 35%, 25% and 33.2%, respectively. The sample selection was made each year, in a random manner per conglomerates, after previous stratification by geographical areas. The sample unit was those schools with over 45 pupils per class, distributed throughout the province of Las Palmas. The confidence level for overall data was 95.5% and the margin of error +/- 2. INTERVENTIONS: The tuberculin tests were performed by specifically contracted and trained doctors and DUE (nurses) at Health Centres, belonging to Primary Care and town councils. The technique used for the tuberculin survey was the intradermal injection of 0.1 ml of PPD which contained 2 units of PPD-RT 23 with Tween-80, with a reading at 72 hours, when a reaction of 5 mm or over was considered positive. To calculate RAI the formula proposed by Styblo was used. RESULTS: The prevalence of tubercular infection in the province of Las Palmas was 0.71% (0.52-0.90) in 1990 and 1.18% (0.75-1.61) in 1993. RAI was 0.11% in 1990 and 0.18% in 1993. CONCLUSIONS: It was almost impossible to make any comparisons with other similar studies because of the lack of homogeneous criteria. Both the prevalence and the risk of tubercular infection in Las Palmas between 1990 and 1993 show an upward tendency. PMID- 7786978 TI - [Physical exercise and disease (and II)]. PMID- 7786979 TI - [Management of atrial fibrillation]. PMID- 7786980 TI - [Arterial hypertension program: new evaluation strategies]. PMID- 7786981 TI - [Referrals from primary care to rheumatology]. PMID- 7786983 TI - Modelling progression of CD4-lymphocyte count and its relationship to survival time. AB - The purpose of this article is to model the progression of CD4-lymphocyte count and the relationship between different features of this progression and survival time. The complicating factors in this analysis are that the CD4-lymphocyte count is observed only at certain fixed times and with a high degree of measurement error, and that the length of the vector of observations is determined, in part, by the length of survival. If probability of death depends on the true, unobserved CD4-lymphocyte count, then the survival process must be modelled. Wu and Carroll (1988, Biometrics 44, 175-188) proposed a random effects model for two-sample longitudinal data in the presence of informative censoring, in which the individual effects included only slopes and intercepts. We propose methods for fitting a broad class of models of this type, in which both the repeated CD4 lymphocyte counts and the survival time are modelled using random effects. These methods permit us to estimate parameters describing the progression of CD4 lymphocyte count as well as the effect of differences in the CD4 trajectory on survival. We apply these methods to results of AIDS clinical trials. PMID- 7786982 TI - [Suitability of routine screening of tuberculosis at 15 months of age]. PMID- 7786984 TI - A nonparametric analysis of the transmission rate of human immunodeficiency virus from mother to infant. AB - Infants born to mothers who are infected with the human immunodeficiency virus (HIV) may or may not become infected by perinatal transmission. Unfortunately, passively transferred maternal antibodies make it hard to determine the infant's infection status from HIV antibody testing, because shortly after birth it is not possible to distinguish passively transferred maternal antibodies from antibodies produced by an infected infant. Usually, the infection status is unobservable for each infant, unless the infant reaches the age of 15 months or develops an HIV related disease such as the acquired immunodeficiency syndrome (AIDS). Traditionally, statistical analyses of the perinatal transmission rate of HIV are based on infants who had been born at least 15 months before the date of analysis. Such analyses can be both inefficient and biased. In this note, we define a mixture model underlying the onset time of AIDS and then obtain the nonparametric maximum likelihood estimators of the HIV transmission rate and of the distribution function of AIDS onset time for infected infants. Nonparametric tests are also derived for detecting differences in HIV transmission rates among different groups of infants. Finally, the methods are applied to the Mothers and Infants Cohort Study in New York City. The transmission rate of HIV from infected mothers to their infants was estimated to be 30.0% with 95% confidence interval (22.3%, 39.1%). PMID- 7786986 TI - Exact permutational tests for group sequential clinical trials. AB - An efficient numerical algorithm is developed for computing stopping boundaries for group sequential clinical trials. Patients arrive in sequence, and are randomized to one of two treatments. The data are monitored at interim time points, with a fresh block of patients entering the study from one monitoring point to the next. The stopping boundaries are derived from the exact joint permutational distribution of the linear rank statistics observed across all the monitoring times. Specifically, the algorithm yields the exact boundary generating function, Pr(W1 < b1, W2 < b2, ..., Wi-1 < bi-1, Wi = wi), where Wj is the linear rank statistic at the jth interim time point. The distribution theory is based on assigning ranks after pooling all the patients who have entered the study, and then permuting the patients to the two treatments independently within each block of newly arrived patients. The methods are applicable for an arbitrary number of monitoring times, which need not be specified at the start of the study. The data may be continuous or categorical, and censored or uncensored. The randomization rule for treatment allocation can be adaptive. The algorithm is especially useful during the early stages of a clinical trial, when very little data have been gathered, and stopping boundaries are based on the extreme tails of the relevant boundary generating function. In that case the corresponding large-sample theory is not very reliable. To illustrate the techniques we present a group sequential analysis of a recently completed study by the Eastern Cooperative Oncology Group. PMID- 7786985 TI - Evaluation of experiments with adaptive interim analyses. AB - A general method for statistical testing in experiments with an adaptive interim analysis is proposed. The method is based on the observed error probabilities from the disjoint subsamples before and after the interim analysis. Formally, an intersection of individual null hypotheses is tested by combining the two p values into a global test statistic. Stopping rules for Fisher's product criterion in terms of critical limits for the p-value in the first subsample are introduced, including early stopping in the case of missing effects. The control of qualitative treatment-stage interactions is considered. A generalization to three stages is outlined. The loss of power when using the product criterion instead of the optimal classical test on the whole sample is calculated for the test of the mean of a normal distribution, depending on increasing proportions of the first subsample in relation to the total sample size. An upper bound on the loss of power due to early stopping is derived. A general example is presented and rules for assessing the sample size in the second stage of the trial are given. The problems of interpretation and precautions to be taken for applications are discussed. Finally, the sources of bias for estimation in such designs are described. PMID- 7786987 TI - The use of logistic models for the analysis of codon frequencies of DNA sequences in terms of explanatory variables. AB - The development of the regressive logistic model applicable to the analysis of codon frequencies of DNA sequences in terms of explanatory variables is presented. A codon is a triplet of nucleotides that code for an amino acid, and may be considered as a trivariate response (B1, B2, B3), where Bi (i = 1, 2, 3) is a categorical random variable with values A, C, G, T. The linear order of bases in the DNA and possible statistical dependence of the bases in a given codon make the regressive logistic model a suitable tool for the analysis of codon frequencies. A problem of structural zeros arises from the fact that the stopping codons (terminators) do not code for amino acids; this is solved by normalizing the likelihood function. Codon frequencies may also depend on the function of the gene and they are known to differ between genes of the same genome. Differences also occur between synonymous codons for the same amino acid. Thus, the use of covariates that differ between synonymous codons as well as covariates that are constant within codons of the same amino acid may be useful in explaining the frequencies. As an illustration, the method is applied to the human mitochondrial genome using the following as explanatory variables: (1) TSCORE, a measure of the number of single base mutations required for a given codon to become a terminator; (2) AARISK, an indicator of a codon's ability of changing by a single base substitution to triplets coding for amino acids with very different characteristics; (3) AVDIST, a measure of the typicality of the amino acid coded for by the triplets. The results indicate that models that incorporate dependency structure and covariates are to be preferred to either the models comprising covariates alone or dependency structure alone. PMID- 7786988 TI - Robust variance estimation for the case-cohort design. AB - Large cohort studies of rare outcomes require extensive data collection, often for many relatively uninformative subjects. Sampling schemes have been proposed that oversample certain groups. For example, the case-cohort design of Prentice (1986, Biometrika 73, 1-11) provides an efficient method of analysis of failure time data. However, the variance estimate must explicitly correct for correlated score contributions. A simple robust variance estimator is proposed that allows for more complicated sampling mechanisms. The variance estimate uses a jackknife estimate of the variance of the individual influence function and is shown to be equivalent to a robust variance estimator proposed by Lin and Wei (1989, Journal of the American Statistical Association 84, 1074-1078) for the standard Cox model. Simulation results indicate excellent agreement with corrected asymptotic estimates and appropriate test size. The technique is illustrated with data evaluating the efficacy of mammography screening in reducing breast cancer mortality. PMID- 7786989 TI - Segregation analysis of case-control data using generalized estimating equations. AB - Generalized estimating equations (GEEs) (Liang and Zeger, 1986, Biometrika 73, 13 22) are used to fit genetic models to binary disease data for families of subjects in case-control studies. The GEEs include model specification of both the disease probabilities and the two-way (and possibly three-way) correlation coefficients of the family disease data. These quantities are modelled as nonlinear functions of unobserved genotypes, observed environmental covariates, and the unknown parameters; the functions reflect the method used to ascertain the family data. Goodness of fit is tested by allowing more flexible forms for the correlation coefficients, regressing them against covariates specific to the relevant pair (or triple) of family members. The approach is applied to family data obtained from simulated and real case-control studies. This semiparametric approach is less dependent on unverifiable assumptions and more computationally tractable than other methods for segregation analysis. PMID- 7786991 TI - Causal nonresponse models for repeated categorical measurements. AB - This paper uses causal models for nonresponse (Fay, 1986, Journal of the American Statistical Association 81, 354-365) to extend the conditional likelihood procedure for repeated categorical outcome variables to allow for nonrandomly missing data. The extension based on causal models is similar to the log-linear approach presented by Conaway (1992, Journal of the American Statistical Association, 87, 817-824), but has the advantage that the parameters are directly interpretable in terms of the distribution of the outcome variables. As with log linear model approach, all of the computations can be done with standard statistical software. The methods are first described in terms of a simple example with three binary responses with no covariates and then are applied to a more complicated example. A simulation study evaluates the properties of the estimates based on the proposed method. PMID- 7786990 TI - Operating characteristics of a rank correlation test for publication bias. AB - An adjusted rank correlation test is proposed as a technique for identifying publication bias in a meta-analysis, and its operating characteristics are evaluated via simulations. The test statistic is a direct statistical analogue of the popular "funnel-graph." The number of component studies in the meta-analysis, the nature of the selection mechanism, the range of variances of the effect size estimates, and the true underlying effect size are all observed to be influential in determining the power of the test. The test is fairly powerful for large meta analyses with 75 component studies, but has only moderate power for meta-analyses with 25 component studies. However, in many of the configurations in which there is low power, there is also relatively little bias in the summary effect size estimate. Nonetheless, the test must be interpreted with caution in small meta analyses. In particular, bias cannot be ruled out if the test is not significant. The proposed technique has potential utility as an exploratory tool for meta analysts, as a formal procedure to complement the funnel-graph. PMID- 7786992 TI - Influence diagnostics for generalized linear measurement error models. AB - We study influence diagnostics for generalized linear models when the true covariates are unobservable but measured with error. Based on the bias-corrected estimation of model parameters, diagnostic measures are developed to identify outlying and influential observations. The magnitude of influence is then assessed via a simulated envelope approach. The proposed diagnostic procedure is illustrated on two examples. PMID- 7786993 TI - Pooled population parameter from mark-recapture data. AB - The reduced capture history (RCH), compiled from complete capture histories of uniquely marked animals, for a given pooling interval contains the same information as would be obtained from experiments where (i) a single sample lasts the duration of the pooling interval; (ii) an identical batch mark is applied to animals captured in a series of samples carried out during the pooling interval. For stationary populations, biases are calculated for the RCH estimates for all parameters in the Jolly-Seber (J-S) model. The results are verified using simulation. The biases are functions of the survival and capture probabilities and the degree of pooling; they are less than 5% for the total population, birth and survival rates, and probability of capture during the pooling interval if the mortality and capture probabilities do not exceed about 50% per pooling interval. The marked population, marked fraction, and probability of recapture cannot estimated directly by the RCH method but can be obtained iteratively from the bias formulae. The biases in other parameters can be reduced by the same procedure. Alternative estimates are derived that are not detectably biased, for any estimate, for mortality and capture probability up to about 60% per pooling period. The new estimates have higher sample variances than the RCH estimates, but for large populations with high mortalities and capture probabilities the difference is small. PMID- 7786994 TI - On inconsistency of Breslow's estimator as an estimator of the hazard rate in the Cox model. AB - In the Cox proportional hazards model, Breslow's estimator of the cumulative hazard function is well known. This estimator is sometimes presented in such a way that it appears to offer a method of estimating the hazard rate function as well. We state and prove an asymptotic result for this estimator of the hazard rate, which shows that the estimator is inconsistent, and that it is asymptotically unbiased. PMID- 7786995 TI - Guidelines for monitoring efficacy and toxicity responses in clinical trials. AB - There is currently a need for clinical trial methodology that allows formal consideration of toxicity responses. Since a complete evaluation of an experimental therapy addresses both relative efficacy and relative toxicity, general methods for handling bivariate response data are of interest. A procedure for sequentially analysing both efficacy and toxicity data is presented. The procedure is designed to allow early termination due to efficacy results, toxicity results, or both. The method is based on modified marginal sequential analyses, accounting for bivariate correlated responses and multiple analyses over time. The theory is presented in the context of normally distributed responses. Extensions to bivariate failure time data are indicated and an example from a kidney transplant study demonstrates the procedure. PMID- 7786996 TI - On a truncation-flexible repeated significance test. AB - A repeated significance test for the mean of a normal distribution with guaranteed Type I error rate not depending on the truncation point is presented. The type of design has the advantage that it may be applied to define a sequential test based on accumulating data, applicable to a wide range of variables of which the fixed-sample-size test would have been based on the standard normal, without the requirement that the covariance structure of the sequence by computed explicitly. The test is shown to be especially convenient for certain types of ongoing survival studies, and for the problem of testing for differences in means or proportions, and appears to have operating characteristics similar to those of standard repeated significance tests with corresponding truncation points. PMID- 7786997 TI - On the likelihood ratio test statistic for the number of components in a normal mixture of unequal variances. AB - An important but difficult problem in practice is to determine the number of components in a normal mixture model with unequal variances. When the likelihood ratio test statistic--21og lambda is used, it is unbounded above and fails to satisfy standard regularity conditions. A restricted maximization procedure must therefore be used, which makes the procedure ad hoc. A consequence of this may explain the discrepancies among the simulation results of previous investigations. PMID- 7786998 TI - A note on the bias of estimators with missing data. AB - It is well known that many standard analyses, including maximum likelihood estimation and the generalized estimating equation approach (Liang and Zeger, 1986, Biometrika 73, 13-22) can result in biased estimation when there are missing observations. In such cases it is of interest to calculate the magnitude of the bias incurred under specific assumptions about the process generating the full data and the nonresponse mechanism. In this paper we give a condition that identifies the limit in probability of estimators that are solutions of estimating equations computed from the incomplete data. With discrete data, this condition suggests a simple algorithm to compute the asymptotic bias of these estimators that can be easily implemented with existing statistical software. We illustrate our approach with asthma prevalence data in children. PMID- 7786999 TI - Variance components testing in the longitudinal mixed effects model. AB - This article discusses the asymptotic behavior of likelihood ratio tests for nonzero variance components in the longitudinal mixed effects linear model described by Laird and Ware (1982, Biometrics 38, 963-974). Our discussion of the large-sample behavior of likelihood ratio tests for nonzero variance components is based on the results for nonstandard testing situations by Self and Liang (1987, Journal of the American Statistical Association 82, 605-610). PMID- 7787000 TI - Heterogeneity models of disease susceptibility, with application to diabetic nephropathy. AB - It is not, in general, possible to include all relevant risk factors in a model of survival or disease incidence. This heterogeneity must be accounted for in the interpretation, as it can imply otherwise unexpected results. This is illustrated by diabetic nephropathy, a serious complication experienced by some diabetic patients. A mathematical model with varying susceptibility can explain that the incidence increases until 20 years duration of diabetes and later decreases. The hospital-based data cover patients diagnosed during 1933-1972. They are interval censored, because early detection of nephropathy requires chemical analysis of urine samples. The data are consistent with a model where less than half of the patients are susceptible, and for each of these the hazard is increasing. The estimated degree of heterogeneity markedly depends on the assumed model. The dependence on age at onset and calendar time of onset is examined. The highest risk is seen at onset age 13-17 years, and the risk decreases with calendar time. The effect of covariates on the hazard is markedly different for the various models, but this is partly a matter of parametrization, as the disagreement is reduced by a reparametrization inspired by accelerated failure time models. PMID- 7787002 TI - Statistical analysis of food webs. AB - The numbers of species in different trophic levels of a food web are modeled as a trinomial random vector, with cell probabilities potentially depending on the total number of species in the web. A maximum likelihood method is developed to test the hypothesis that the fractions of species in different levels are independent of the total number of species. The method is applied to a data set whose properties have been debated in the literature, and it is shown to be a powerful alternative to the simple linear regression approach used in previous analyses. PMID- 7787001 TI - Testing for segregation distortion in the HLA complex. AB - One of the long-standing issues in HLA research is whether there is segregation distortion in the HLA complex in human populations. In this paper we study some simple statistical models aimed at detecting segregation distortion. We present a statistic to test the Mendelian null hypothesis of equal transmission probabilities. To assess the possible contribution of multiple alleles to segregation distortion, we employ a specific log-linear model for transmission probabilities equivalent to the Bradley-Terry model in the literature of paired comparisons. We also provide a simple method for detecting a single allele effect, if present. PMID- 7787003 TI - Regression analysis of censored and truncated data: estimating reporting-delay distributions and AIDS incidence from surveillance data. AB - AIDS surveillance provides a vital source of information for health departments to assess the AIDS epidemic and to plan for future health-care needs. However, the use of surveillance data requires proper adjustments for the underreporting of AIDS cases caused by the delay in reporting diagnosed AIDS cases to the surveillance system. The statistical problem of adjusting for this underreporting concerns making inferences about an unobservable random sample of which only a portion is observed in a chronologic time interval defined by the analysis. Most regression methods for making inferences using right-truncated data employ a reverse-time hazard function, which requires that the observed data be transformed so that methods for left-truncated data can be applied. In this paper, we discuss fitting regression models to data that can be truncated and even censored in arbitrary intervals. The proposed methodology was applied to the national AIDS surveillance data provided by the Centers for Disease Control to analyze the trend of delays over chronologic time and variation among different geographic regions as well as across risk groups. PMID- 7787004 TI - A cautionary note on applying scores in stratified data. AB - When rank tests are used to analyze stratified data, three methods for assigning scores to the observations have been proposed: (S) independently within each stratum (see Lehmann, 1975, Nonparametrics: Statistical Methods Based on Ranks; San Francisco: Holden-Day); (A) after aligning the observations within each stratum and then pooling the aligned observations (Hodges and Lehmann, 1962, Annals of Mathematical Statistics 33, 482-497); and (P) after pooling the observations across all strata (that is, without alignment) (Mantel, 1963, Journal of the American Statistical Association 58, 690-700; Mantel and Ciminera, 1979, Cancer Research 39, 4308-4315). Test statistics are formed for each method by combining the stratum-specific linear rank tests using the assigned scores. We show that method P is sensitive to the score function used in the case of two moderately sized strata. In general, we recommend methods S and A for use with moderate to large-sized strata. PMID- 7787005 TI - The world of biometry. AB - The International Biometric Society is an international society for the advancement of biological science through the development of quantitative theories and the application, development and dissemination of effective mathematical and statistical techniques. We consider some of the nonscientific and scientific issues being addressed by researchers in and across Regions and Groups of our Biometric world. These run the gamut of theoretical to applied mathematics and statistics with the applications spanning many fields and, not surprisingly, forming a rich source of new theoretical developments. PMID- 7787006 TI - A random-effects ordinal regression model for multilevel analysis. AB - A random-effects ordinal regression model is proposed for analysis of clustered or longitudinal ordinal response data. This model is developed for both the probit and logistic response functions. The threshold concept is used, in which it is assumed that the observed ordered category is determined by the value of a latent unobservable continuous response that follows a linear regression model incorporating random effects. A maximum marginal likelihood (MML) solution is described using Gauss-Hermite quadrature to numerically integrate over the distribution of random effects. An analysis of a dataset where students are clustered or nested within classrooms is used to illustrate features of random effects analysis of clustered ordinal data, while an analysis of a longitudinal dataset where psychiatric patients are repeatedly rated as to their severity is used to illustrate features of the random-effects approach for longitudinal ordinal data. PMID- 7787008 TI - A parametric model for cluster correlated categorical data. AB - A fully parametric copula model for symmetric dependent clustered categorical data is discussed. The model accommodates any marginal regression models of interest and admits a broad range of within-cluster association. The form of the distribution is independent of cluster size and may be used to model data with varying cluster sizes. The model contains an association parameter that is estimated from the data to give a measure of strength of the within-cluster association and also a test of independence. Two examples are given to illustrate methods. PMID- 7787007 TI - An application of maximum likelihood and generalized estimating equations to the analysis of ordinal data from a longitudinal study with cases missing at random. AB - Data are analysed from a longitudinal psychiatric study in which there are no dropouts that do not occur completely at random. A marginal proportional odds model is fitted that relates the response (severity of side effects) to various covariates. Two methods of estimation are used: generalized estimating equations (GEE) and maximum likelihood (ML). Both the complete set of data and the data from only those subjects completing the study are analysed. For the completers only data, the GEE and ML analyses produce very similar results. These results differ considerably from those obtained from the analyses of the full data set. There are also marked differences between the results obtained from the GEE and ML analysis of the full data set. The occurrence of such differences is consistent with the presence of a non-completely-random dropout process and it can be concluded in this example that both the analyses of the completers only and the GEE analysis of the full data set produce misleading conclusions about the relationships between the response and covariates. PMID- 7787009 TI - Exact analysis for paired binary data. AB - This paper provides an efficient algorithm to generate exact distributions for the bivariate logistic model with common and sub-unit-specific covariates. The algorithm can be used to analyze correlated paired binary response data from studies lacking a large sample size. Possible applications include a clinical trial with two distinct binary outcomes, a binary outcome cross-over or two-time point cohort study, and a pair-matched prospective study with binary outcome. Analysis of data from an ophthalmologic study is provided to illustrate the method. Extension to three or more correlated binary responses is also outlined. PMID- 7787010 TI - Multivariate survival analysis using piecewise gamma frailty. AB - In this note we propose a frailty model called piecewise gamma frailty for correlated survival data with random effects having a nested structure. In frailty models, a dependence function defined as a hazard ratio of one member given the failure time of another member in a unit is determined by the distributional assumptions on frailty. In the piecewise gamma frailty model, the nested structure of random effects or frailty allows the dependence function to vary over the time periods. This model includes existing models such as the piecewise exponential model (Breslow, 1974, Biometrics 30, 89-100) and the gamma frailty model (Clayton, 1978, Biometrika 65, 141-151; Oakes, 1982, Journal of the Royal Statistical Society, Series B 44, 414-428) as special cases. A study of familial aggregation of epilepsy is used to illustrate the proposed method. PMID- 7787011 TI - Iterative generalized least squares for meta-analysis of survival data at multiple times. AB - A method is presented for joint analysis of survival proportions reported at multiple times in published studies to be combined in a meta-analysis. Generalized least squares is used to fit linear models including between-trial and within-trial covariates, using current fitted values iteratively to derive correlations between times within studies. Multi-arm studies and nonrandomized historical controls can be included with no special handling. The method is illustrated with data from two previously published meta-analyses. In one, an early treatment difference is detected that was not apparent in the original analysis. PMID- 7787012 TI - Intracellular calcium levels correlate with speed and persistent forward motion in migrating neutrophils. AB - The relationship between cytosolic free calcium concentration ([Ca2+]i) and human neutrophil motility was studied by video microscopy. Neutrophils stimulated by a uniform concentration of an N-formylated peptide chemoattractant (f-Met-Leu-Phe) were tracked during chemokinetic migration on albumin, fibronectin, and vitronectin. [Ca2+]i buffering with quin2 resulted in significant decreases in mean speed on albumin. To further characterize the relationship between [Ca2+]i changes and motility we carried out a cross-correlation analysis of [Ca2+]i with several motility parameters. Cross-correlations between [Ca2+]i and each cell's speed, angle changes, turn strength, and persistent forward motion revealed (i) a positive correlation between [Ca2+]i and cell speed (p < 0.05), (ii) no significant correlation between turns and calcium spikes, and (iii) the occurrence of turns during periods of low speed. Significant negative correlations between [Ca2+]i and angle change were noted on the high adhesion substrates vitronectin and fibronectin but not on the low adhesion substrate albumin. These data imply that there is a general temporal relationship between [Ca2+]i, speed, and persistent motion. However, the correlations are not sufficiently strong to imply that changes in [Ca2+]i are required proximal signals for velocity changes. PMID- 7787013 TI - Cell fission and formation of mini cell bodies by high frequency alternating electric field. AB - We report the use of high frequency alternating electric fields (AC) to induce deformation of sea urchin eggs, leading to budding of membrane vesicles or fission of cells. Several mini cell bodies can be prepared from a single egg by carefully manipulating the frequency and amplitude of the AC field and the ratio between the interelectrode spacing and the cell diameter, alpha. alpha values between 2.2 and 3.5 have been found to be optimal for inducing fission of sea urchin eggs. In a typical experiment, a sea urchin egg (diameter = 75 microns), suspended in a low ionic medium (conductance < 2 mS/m), was located under the microscope between two platinum wire electrodes, separated by a distance of approximately 200 microns. A medium strength AC field (< 100 V/cm at 2 MHz) was applied to attract the egg to one of the two electrodes via dielectrophoresis. This process took place in a few seconds. The voltage was then slowly increased to approximately 1000 V/cm over approximately 30 s. The cell elongated and separated into two fragments, the larger one containing the nucleus. When the field was turned off, the mother cell and the daughter vesicle retracted to form spherical mini cell bodies that appear to be stable as assessed by the absence of swelling for the duration of the experiment (approximately 15 min). This indicates that membranes of these mini cell bodies were not leaky to ions and small molecules. This procedure could be repeated a few times to make several mini cell bodies from a single egg. With practice, several minicell bodies could also be prepared in a single fission experiment by adjusting the field parameters and the a value. Cell fission is a result of the mechanical stress produced by the AC field. These procedures may be used to prepare mini membrane vesicles for voltage clamp experiments or to perform microsurgical manipulation of cells, embryos, or chromosomes. PMID- 7787014 TI - Approximating the effects of diffusion on reversible reactions at the cell surface: ligand-receptor kinetics. AB - We consider the problem of determining the time dependence of the bound ligand concentration for the reversible binding of a diffusing monovalent ligand to receptors uniformly distributed over the surface of a spherical cell. We start by formulating a boundary value problem that captures the essential physics of this situation. We then introduce a systematic approximation scheme based on the method of weighted residuals. By this means we convert the initial boundary value problem into a simpler problem that requires solving only a small number of ordinary differential equations. We show how, at the lowest order of approximation, the method can be used to obtain modified chemical rate equations where, in place of fundamental rate constants, effective rate coefficients appear. These rate coefficients are functions of the ligand diffusion coefficient, the cell radius, the receptor density and other variables. We compare exact and approximate solutions and discuss under what conditions the approximate equations can be used. We also apply the method of weighted residuals to obtain approximate descriptions of the binding kinetics when (1) there are two different cell surface receptor populations that bind the ligand and (2) the cell secretes a ligand that can bind back to receptors on the cell (autocrine binding). PMID- 7787015 TI - Dynamic and elastic properties of F-actin: a normal-modes analysis. AB - We examine the dynamic, elastic, and mechanical consequences of the proposed atomic models of F-actin, using a normal mode analysis. This initial analysis is done in vacuo and assumes that all monomers are rigid and equivalent. Our computation proceeds from the atomic level and, relying on a single fitting parameter, reproduces various experimental results, including persistence lengths, elastic moduli, and contact energies. The computations reveal modes of motion characteristic to all polymers, such as longitudinal pressure waves, torsional waves, and bending, as well as motions unique to F-actin. Motions typical to actin include a "groove-swinging" motion of the two long-pitch helices, as well as an axial slipping motion of the two strands. We prepare snapshots of thermally activated filaments and quantify the accumulation of azimuthal angular "disorder," variations in cross-over lengths, and various other fluctuations. We find that the orientation of a small number of select residues has a surprisingly large effect on the filament flexibility and elasticity characteristics. PMID- 7787016 TI - An easy-to-use model for O2 supply to red muscle. Validity of assumptions, sensitivity to errors in data. AB - An easy-to-use capillary cylinder model of O2 supply to muscle is presented that considers all those factors that are known to be most important for realistic results: (1) red blood cell (RBC) O2 unloading along the capillary, (2) effects of the particulate nature of blood, (3) free and hemoglobin-facilitated O2 diffusion and reaction kinetics inside RBCs, (4) free and myoglobin-facilitated O2 diffusion inside the muscle cell, and (5) carrier-free region separating RBC and tissue. In a first approach, a highly simplified yet reasonably accurate treatment of the complex three-dimensional oxygen diffusion field in and next to capillaries is employed. As an alternative, a more realistic description using RBC/capillary diffusing capacity has been included. Model development proceeds step by step and is designed to be easily comprehensible for a broad readership. In spite of the number of features accounted for, the model is simple to apply, even for scientists not specialized in the field of modeling. PO2 distributions calculated by the model are in good qualitative agreement with experimental data and with former modelling results. By means of suitable extensions to the model that are also developed it is shown for a wide range of muscle performances that quite generally the following complication may be neglected safely: (1) complexity of O2 diffusion field near capillaries, (2) deviations of capillary domain cross sections from the circular shape, (3) O2 diffusion parallel to the capillary direction, and (4) PO2 dependence of O2 consumption rate. Finally, a sensitivity analysis is performed in which propagation of errors in the input data into the results is investigated. The interpretation of the calculated sensitivities gives insights in the specific dependencies of muscular O2 supply on the various input parameters. Moreover, basic interrelations governing carrier facilitated diffusional O2 transport to muscle become apparent and are discussed. PMID- 7787017 TI - Molecular dynamics study of the 13-cis form (bR548) of bacteriorhodopsin and its photocycle. AB - The structure and the photocycle of bacteriorhodopsin (bR) containing 13-cis,15 syn retinal, so-called bR548, has been studied by means of molecular dynamics simulations performed on the complete protein. The simulated structure of bR548 was obtained through isomerization of in situ retinal around both its C13-C14 and its C15-N bond starting from the simulated structure of bR568 described previously, containing all-trans,15-anti retinal. After a 50-ps equilibration, the resulting structure of bR548 was examined by replacing retinal by analogues with modified beta-ionone rings and comparing with respective observations. The photocycle of bR548 was simulated by inducing a rapid 13-cis,15-anti-->all trans,15-syn isomerization through a 1-ps application of a potential that destabilizes the 13-cis isomer. The simulation resulted in structures consistent with the J, K, and L intermediates observed in the photocycle of bR548. The results offer an explanation of why an unprotonated retinal Schiff base intermediate, i.e., an M state, is not formed in the bR548 photocycle. The Schiff base nitrogen after photoisomerization of bR548 points to the intracellular rather than to the extracellular site. The simulations suggest also that leakage from the bR548 to the bR568 cycle arises due to an initial 13-cis,15-anti-->all trans,15-anti photoisomerization. PMID- 7787020 TI - Confinement as a determinant of macromolecular structure and reactivity. II. Effects of weakly attractive interactions between confined macrosolutes and confining structures. AB - The effect of weak, nonspecific interaction between molecules confined within restricted elements of volume ("pores") and the boundary surfaces of the pore, upon the reactivity and physical state of the confined molecules, is explored by means of simple models. A confined molecule is represented by a rectangular parallelopiped having one of six orientations aligned with the cartesian coordinate axes, and the confining volume element is represented by a pair of parallel surfaces (planar pore), a tube of square cross section (square pore), or a cubical box (cubical pore). Weak interactions are modeled by square-well potentials having a defined range and well depth. Partition coefficients for distribution of molecules between the bulk and confined phase are calculated using an extension of the statistical-thermodynamic theory of Giddings et al. (1968). It is calculated that surface attraction with a potential of only a few kcal/mol monomer may result in large increases in the extent of self- or heteroassociation of confined molecules (as much as several orders of magnitude in favorable cases) linked to adsorption of the oligomeric species onto boundary surfaces. Calculations are also presented suggesting that surface attraction can lead to deformation of the native structure of adsorbed macromolecules. It is suggested that these findings are relevant to an understanding of the structure of eukaryotic cytoplasm. PMID- 7787018 TI - Distal residue-CO interaction in carbonmonoxy myoglobins: a molecular dynamics study of three distal mutants. AB - Six 90-ps molecular dynamics trajectories, two for each of three distal mutants of sperm whale carbonmonoxy myoglobin, are reported; solvent waters within 16 A of the active site have been included. In both His64GIn trajectories, the distal side chain remains part of the heme pocket, forming a "closed" conformation similar to that of the wild type 64N delta H tautomer. Despite a connectivity more closely resembling the N epsilon H histidine tautomer, close interactions with the carbonyl ligand similar to those observed for the wild type 64N epsilon H tautomer are prevented in this mutant by repulsive interactions between the carbonyl O and the 64O epsilon. The aliphatic distal side chain of the His64Leu mutant shows little interaction with the carbonyl ligand in either His64Leu trajectory. Solvent water molecules move into and out of the active site in the His64Gly mutant trajectories; during all the other carbonmonoxy myoglobin trajectories, including the wild type distal tautomers considered in an earlier work, solvent molecules rarely encroach closer than 6 A of the active site. These results are consistent with a recent structural interpretation of the wild type infrared spectrum, and the current reinterpretation that the distal-ligand interaction in carbonmonoxy myoglobin is largely electrostatic, not steric, in nature. PMID- 7787019 TI - Seven-helix bundles: molecular modeling via restrained molecular dynamics. AB - Simulated annealing via restrained molecular dynamics (SA/MD) has been used to model compact bundles of seven approximately (anti)parallel alpha-helices. Seven such helix bundles occur, e.g., in bacteriorhodopsin, in rhodopsin, and in the channel-forming N-terminal domain of Bacillus thuringiensis delta-endotoxin. Two classes of model are considered: (a) those consisting of seven Ala20 peptide chains; and (b) those containing a single polypeptide chain, made up of seven Ala20 helices linked by GlyN interhelix loops (where N = 5 or 10). Three different starting C alpha templates for SA/MD are used, in which the seven helices are arranged (a) on a left-handed circular template, (b) on a bacteriorhodopsin-like template, or (c) on a zig-zag template. The ensembles of models generated by SA/MD are analyzed in terms of their geometry and energetics, and the most stable structures from each ensemble are examined in greater detail. Structures resembling bacteriorhodopsin and structures resembling delta-endotoxin are both represented among the most stable structures. delta-Endotoxin-like structures arise from both circular and bacteriorhodopsin-like C alpha templates. A third helix-packing mode occurs several times among the stable structures, regardless of the C alpha template and of the presence or absence of interhelix loops. It is characterized by a "4 + 1" core, in which four helices form a distorted left-handed supercoil around a central, buried helix. The remaining two helices pack onto the outside of the core. This packing mode is comparable with that proposed for rhodopsin on the basis of two-dimensional electron crystallographic and sequence analysis studies. PMID- 7787021 TI - Kinetic analysis of barium currents in chick cochlear hair cells. AB - Inward barium current (IBa) through voltage-gated calcium channels was recorded from chick cochlear hair cells using the whole-cell clamp technique. IBa was sensitive to dihydropyridines and insensitive to the peptide toxins omega agatoxin IVa, omega-conotoxin GVIa, and omega-conotoxin MVIIC. Changing the holding potential over a -40 to -80 mV range had no effect on the time course or magnitude of IBa nor did it reveal any inactivating inward currents. The activation of IBa was modeled with Hodgkin-Huxley m2 kinetics. The time constant of activation, tau m, was 550 microseconds at -30 mV and gradually decreased to 100 microseconds at +50 mV. A Boltzmann fit to the activation curve, m infinity, yielded a half activation voltage of -15 mV and a steepness factor of 7.8 mV. Opening and closing rate constants, alpha m and beta m, were calculated from tau m and m infinity, then fit with modified exponential functions. The H-H model derived by evaluating the exponential functions for alpha m and beta m not only provided an excellent fit to the time course of IBa activation, but was predictive of the time course and magnitude of the IBa tail current. No differences in kinetics or voltage dependence of activation of IBa were found between tall and short hair cells. We conclude that both tall and short hair cells of the chick cochlea predominantly, if not exclusively, express noninactivating L-type calcium channels. These channels are therefore responsible for processes requiring voltage-dependent calcium entry through the basolateral cell membrane, such as transmitter release and activation of Ca(2+)-dependent K+ channels. PMID- 7787022 TI - Trimethyloxonium modification of batrachotoxin-activated Na channels alters functionally important protein residues. AB - The extracellular side of single batrachotoxin-activated voltage-dependent Na channels isolated from rat skeletal muscle membranes incorporated into neutral planar lipid bilayers were treated in situ with the carboxyl methylating reagent, trimethyloxonium (TMO). These experiments were designed to determine whether TMO alters Na channel function by a general through-space electrostatic mechanism or by methylating specific carboxyl groups essential to channel function. TMO modification reduced single-channel conductance by decreasing the maximal turnover rate. Modification increased channel selectivity for sodium ions relative to potassium ions as measured under biionic conditions. TMO modification increased the mu-conotoxin (muCTX) off-rate by three orders of magnitude. Modification did not alter the muCTX on-rate at low ionic strength or Na channel voltage-dependent gating characteristics. These data demonstrate that TMO does not act via a general electrostatic mechanism. Instead, TMO targets protein residues specifically involved in ion conduction, ion selectivity, and muCTX binding. These data support the hypothesis that muCTX blocks open-channel current by physically obstructing the ion channel pore. PMID- 7787023 TI - Characterization of complexes formed in fully hydrated dispersions of dipalmitoyl derivatives of phosphatidylcholine and diacylglycerol. AB - The phase diagram of fully hydrated binary mixtures of dipalmitoylphosphatidylcholine (DPPC) with 1,2-dipalmitoylglycerol (DPG) published recently by Lopez-Garcia et al. identifies regions where stoichiometric complexes of 1:1 and 1:2 DPPC:DPG, respectively, are formed. In this study, the structural parameters of the 1:1 complex in the presence of pure DPPC was characterized by synchrotron low angle and static x-ray diffraction methods. Structural changes upon transitions through phase boundaries were correlated with enthalpy changes observed by differential scanning calorimetry in mixtures of DPPC with 5, 7.5, 10, and 20 mol% DPG dispersed in excess water. Phase separation of a complex in gel phase could be detected by calorimetry in the mixture containing 5 mol% DPG but was not detectable by synchrotron low angle x-ray diffraction. Static x-ray measurements show evidence of phase separation, particularly in the reflections indexing chain packing. In the mixture containing 7.5 mol% DPG, two distinct lamellar repeat spacings could be seen in the temperature range from 25 to 34 degrees C. The lamellar spacing of about 6.6 nm was assigned to pure gel phase DPPC because the change in the spacing corresponds with thermal transition of the pure phospholipid, and a longer repeat spacing of about 7.2 nm was assigned to domains of the 1:1 complex of DPPC-DPG. In the temperature range from 34 to 420C, i.e., in the region of coexistence of the ripple phase of DPPC and the gel phase of the complex, a single, rather broad lamellar reflection appears because of superposition of two reflections of DPPC and the complex; the lamellar spacing of DPPC in the ripple phase is similar to that of the gel phase of complex. In the coexistence region of the liquid crystalline phase of DPPC and the gel phase of complex (-42-480C), the lamellar reflections of the both phases are present. The fluidus boundary lies between the coexistence region and the fluid region.In the fluid region (-48-550C), the gel state of complex persists up to the fluidus boundary, whereupon the liquid crystalline state of complex replaces the gel state of the complex. This indicates that the complex is also immiscible with DPPC even above the fluidus boundary at least in the temperature range close to the phase boundary. For mixtures comprising 10 and 20 mol%DPG in DPPC, complex formation is clearly detectable in both the gel region and the coexistence region by x-ray diffraction.Synchrotron x-ray measurements indicate phase separation between pure DPPC and liquid-crystalline complex just above thefluidus boundary. Static, wide angle x-ray measurements also suggest phase separations of the 1:1 complex not only from the gel phase but also the liquid-crystalline phase of pure DPPC. Two distinct diffraction peaks were detected for the mixture of DPPC with 5, 10, and 20 mol% DPG. One is due to the chain spacing of the complex, and the other is due to that of the pure DPPC. In the coexistence region of the liquid-crystalline phase of DPPC and the gel phase of complex, two kinds of diffraction peaks of the hydrocarbon chain of the gel phase complex and the broad scattering profile for the chain melting of DPPC were observed in the wide angle region. Electron density reconstructed from the lamellar reflections indicates that the thicknesses of both the bilayer and the water layer of the gel phase complex are greater than those of the respective thicknesses of gel phase DPPC. PMID- 7787024 TI - Molecular organization and motions of crystalline monoacylglycerols and diacylglycerols: a C-13 MASNMR study. AB - Six saturated acylglycerols (1-myristoyl-sn-glycerol, 1-palmitoyl-sn-glycerol, 1,2-dimyristoyl-sn-glycerol, 1,2-dipalmitoyl-sn-glycerol, 1,2-dipalmitoyl-rac glycerol, and 1,3-dimyristoylglycerol) were studied in their various polymorphic forms (sub-alpha, alpha, beta') by natural abundance C-13 nuclear magnetic resonance (NMR) with magic angle spinning (MASNMR). C-13 MASNMR does not require single crystals and can observe relatively disordered crystals, distinct advantages over crystallographic diffraction methods. Well resolved spectra were obtained for each acylglycerol, and the chemical shifts of corresponding carbons were different for each crystalline phase and the isotropic liquid phase; moreover, in the case of monoacylglycerols, the symmetrically nonequivalent molecules in the same crystalline structure gave distinct C-13 resonances for the same carbon. The C-13 chemical shifts corresponding to each polymorphic phase were interpreted in terms of differences in intramolecular bond distances, intermolecular interactions (such as H bonding), and molecular motions. Mobilities of the glycerol backbone and acyl chains were assessed by the C-13 linewidths and the C-H dipolar relaxation rates. The chemical shift anisotropy(ies) (delta sigma) of the carbonyl group(s) of each acylglycerol was determined from slow-spinning MAS spectra, and was discussed in terms of the conformational and/or motional changes for the carbonyl carbon(s). PMID- 7787027 TI - Three-dimensional structure of lipid vesicles embedded in vitreous ice and investigated by automated electron tomography. AB - Automated electron tomography is shown to be a suitable means to visualize the shape of phospholipid vesicles embedded in vitrified ice. With a slow-scan charge coupled device camera as a recording device, the cumulative electron dose needed to record a data set of 60 projections at a magnification of 20,000X can be kept as low as 15 e-/A2 (or 1500 electrons/nm2). The membrane of the three dimensionally reconstructed vesicles is clearly visible in two-dimensional sections through the three-dimensionally reconstructed volume. Some edges indicating a polygonal shape of the vesicles, frozen from the gel phase, are also clearly recognized. Because of the presently limited tilt angle range (+/- 60 degrees), the upper and lower "caps" of the vesicles (representing about 35% of the surface of the ellipsoidal particles) remain invisible in the three dimensional reconstruction. PMID- 7787026 TI - Voltage sensitivity of the fluorescent probe RH421 in a model membrane system. AB - The voltage sensitivity of the fluorescent styrylpyridinium dye RH421 has been investigated in dimyristoylphosphatidylcholine vesicles by inducing an intramembrane electric field through the binding of the hydrophobic ion tetraphenylborate (TPB). To assess the probability of electrochromic and solvatochromic mechanisms for the dye response, the ground-state dipole moment of the dye in chloroform solution was determined from dielectric constant measurements to be 12 (+/- 1) Debye, and the change in dipole moment upon excitation was calculated from measurements of the Stokes shift in solvents of varying polarity to be 25 (+/- 11) Debye. As well as causing absorbance and fluorescence changes of membrane-bound dye, the TPB-induced electrical field was found to reduce significantly the pKa of the dye. The pH at which experiments are carried out is, thus, an important factor in determining the amplitude of the voltage-induced absorbance and fluorescence changes. The observed absorbance changes induced by the field are inconsistent with a pure electrochromic mechanism. A reorientation/solvatochromic mechanism, whereby the electrical field reorients the dye molecules so that they experience a change in polarity of their lipid environment is likely to make a significant contribution to both the spectral changes and to the field effect on the acid-base properties of the dye. PMID- 7787025 TI - Macro-ripple phase formation in bilayers composed of galactosylceramide and phosphatidylcholine. AB - As determined by freeze fracture electron microscopy, increasing levels of bovine brain galactosylceramide (GalCer) altered the surface structure of 1-palmitoyl-2 oleoyl-phosphatidylcholine (POPC) bilayers by inducing a striking "macro-ripple" phase in the larger, multilamellar lipid vesicles at GalCer mole fractions between 0.4 and 0.8. The term "macro-ripple" phase was used to distinguish it from the P beta' ripple phase observed in saturated, symmetric-chain length phosphatidylcholines. Whereas the P beta' ripple phase displays two types of corrugations, one with a wavelength of 12-15 nm and the other with a wavelength of 25-35 nm, the macro-ripple phase occurring in GalCer/POPC dispersions was of one type with a wavelength of 100-110 nm. Also, in contrast to the extended linear arrays of adjacent ripples observed in the P beta' ripple phase, the macro ripple phase of GalCer/POPC dispersions was interrupted frequently by packing defects resulting from double dislocations and various disclinations and, thus, appeared to be continuously twisting and turning. Control experiments verified that the macro-ripple phase was not an artifact of incomplete lipid mixing or demixing during preparation. Three different methods of lipid mixing were compared: a spray method of rapid solvent evaporation, a sublimation method of solvent removal, and solvent removal using a rotary evaporation apparatus. Control experiments also revealed that the macro-ripple phase was observed regardless of whether lipid specimens were prepared by either ultra-rapid or manual plunge freezing methods as well as either in the presence or absence of the cryo-protectant glycerol. The macro-ripple phase was always observed in mixtures that were fully annealed by incubation above the main thermal transition of both POPC and bovine brain GalCer before rapid freezing. If the GalCer mixed with POPC contained only nonhydroxy acyl chains or only 2-hydroxy acyl chains, then the occurrence of macro-ripple phase decreased dramatically. PMID- 7787028 TI - Temperature- and pressure-dependent phase behavior of monoacylglycerides monoolein and monoelaidin. AB - We used x-ray and neutron diffraction to study the temperature- and pressure dependent structure and phase behavior of the monoacylglycerides 1-monoelaidin (ME) and 1-monoolein (MO) in excess water. The monoacylglycerides were chosen for investigation of their phase behavior because they exhibit mesomorphic phases with one-, two-, and three-dimensional periodicity, such as lamellar, an inverted hexagonal and bicontinuous cubic phases, in a rather easily accessible temperature and pressure range. We studied the structure, stability, and transformations of the different phases over a wide temperature and pressure range, explored the epitaxial relations that exist between different phases, and established a relationship between the chemical structure of the lipid molecules and their phase behavior. For both systems, a temperature-pressure phase diagram has been determined in the temperature range from 0 to 100 degrees C at pressures from ambient up to 1400 bar, and drastic differences in phase behavior are found for the two systems. In MO-water dispersions, the cubic phase Pn3m extends over a large phase field in the T,p-plane. At temperatures above 95 degrees C, the inverted hexagonal phase is found. In the lower temperature region, a crystalline lamellar phase is induced at higher pressures. The phases found in ME-water include the lamellar crystalline Lc phase, the L beta gel phase, the L alpha liquid-crystalline phase, and two cubic phases belonging to the crystallographic space groups Im3m and Pn3m. In addition, the existence of metastable phases has been exploited. Between coexisting metastable cubic structures, a metric relationship has been found that is predicted theoretically on the basis of the curvature elastic energy approximation only. PMID- 7787029 TI - Myosin binding-induced cooperative activation of the thin filament in cardiac myocytes and skeletal muscle fibers. AB - Myosin binding-induced activation of the thin filament was examined in isolated cardiac myocytes and single slow and fast skeletal muscle fibers. The number of cross-bridge attachments was increased by stepwise lowering of the [MgATP] in the Ca(2+)-free solution bathing the preparations. The extent of thin filament activation was determined by monitoring steadystate isometric tension at each MgATP concentration. As pMgATP (where pMgATP is -log [MgATP]) was increased from 3.0 to 8.0, isometric tension increased to a peak value in the pMgATP range of 5.0-5.4. The steepness of the tension-pMgATP relationship, between the region of the curve where tension was zero and the peak tension, is hypothesized to be due to myosin-induced cooperative activation of the thin filament. Results showed that the steepness of the tension-pMgATP relationship was markedly greater in cardiac as compared with either slow or fast skeletal muscle fibers. The steeper slope in cardiac myocytes provides evidence of greater myosin binding-induced cooperative activation of the thin filament in cardiac as compared with skeletal muscle, at least under these experimental conditions of nominal free Ca2+. Cooperative activation is also evident in the tension-pCa relation, and is dependent upon thin filament molecular interactions, which require the presence of troponin C. Thus, it was determined whether myosin-based cooperative activation of the thin filament also requires troponin C. Partial extraction of troponin C reduced the steepness of the tension-pMgATP relationship, with the effect being significantly greater in cardiac than in skeletal muscle. After partial extraction of troponin C, muscle type differences in the steepness of the tension-pMgATP relationship were no longer apparent, and reconstitution with purified troponin C restored the muscle lineage differences. These results suggest that, in the absence of Ca2+, myosin-mediated activation of the thin filament is greater in cardiac than in skeletal muscle, and this apparent cooperativity requires the presence of troponin C on thin filament regulatory strands. PMID- 7787030 TI - Effects of a non-divalent cation binding mutant of myosin regulatory light chain on tension generation in skinned skeletal muscle fibers. AB - Each myosin molecule contains two heavy chains and a total of four low-molecular weight light chain subunits, two "essential" and two "regulatory" light chains (RLCs). Although the roles of myosin light chains in vertebrate striated muscle are poorly understood at present, recent studies on the RLC have suggested that it has a modulatory role with respect to Ca2+ sensitivity of tension and the rate of tension development, effects that may be mediated by Ca2+ binding to the RLC. To examine possible roles of the RLC Ca2+/Mg2+ binding site in tension development by skeletal muscle, we replaced endogenous RLC in rabbit skinned psoas fibers with an avian mutant RLC (D47A) having much reduced affinity for divalent cations. After replacement of up to 80% of the endogenous RLC with D47A RLC, maximum tension (at pCa 4.5) was significantly reduced compared with preexchange tension, and the amount of decrease was directly related to the extent of D47A exchange. Fiber stiffness changed in proportion to tension, indicating that the decrease in tension was due to a decrease in the number of tension-generating cross-bridges. Decreases in both tension and stiffness were substantially, although incompletely, reversed after reexchange of native RLC for D47A. RLC exchange was also performed using a wild-type RLC. Although a small decrease in tension was observed after wild-type RLC exchange, the decrease was not proportional to the extent of RLC exchange and was not reversed by reexchange of the native RLC. D47A exchange also decreased the Ca2+ sensitivity of tension and reduced the apparent cooperativity of tension development. The results suggest that divalent cation binding to myosin RLC plays an important role in tension generation in skeletal muscle fibers. PMID- 7787031 TI - Calibration of indo-1 and resting intracellular [Ca]i in intact rabbit cardiac myocytes. AB - Fluorescent Ca indicators have been extremely valuable in understanding intracellular [Ca] ([Ca]i) regulation in many cell types. The calibration of these indicators in the intracellular environment, however, has been a continuous challenge. We performed in vivo calibrations of indo-1 in isolated rabbit ventricular myocytes loaded with the acetoxymethylester form of indo-1 and used the perforated patch variation of whole cell voltage clamp. Voltage, [Na], and [K] gradients were eliminated to approach equilibrium. We also took advantage of the powerful Na/Ca exchange in cardiac myocytes so that [Ca]i would be equilibrated with [Ca]o (because there was no [Na] or voltage gradient). The equilibration of [Na] and [Ca] across the membrane was tested by measuring the reversal potential of Na current and poking the cell to test for changes in [Ca]i dependent fluorescence ratio. The apparent dissociation constant, Kd for indo-1 in the cellular environment was 844 nM, which is approximately 2-3 times higher than that in aqueous solutions. In a separate series of experiments, a null point approach was used to determine the [Ca]i in intact cells at rest for very long periods (82 +/- 6 nM). This is lower than that measured 15 s after a train of steady-state twitches ([Ca]i = 294 +/- 53 nM). These experiments also allowed the direct assessment of the shortening versus [Ca]i relationship in intact cells. PMID- 7787033 TI - Comparison of rotation models for describing DNA conformations: application to static and polymorphic forms. AB - A new method, based on a space-fixed rotation axis, or local helix axis, is proposed for the calculation of the relative orientation variables for a sequence of base pairs. With this method, orientation variables are determined through the rotation of a base pair about this axis. These variables uniquely determine a set of helical variables, similar to the roll, tilt, and twist, commonly used for a description of spatial orientations of internally rigid base pairs. The proposed identification of roll and tilt with the direction cosines of the space-fixed rotation axis agrees well with their customary definitions as the openings of the angles between adjoining base pairs toward the minor groove and toward the ascending (5' to 3') backbone strand, respectively. These new variables permit a more direct physical comprehension of DNA conformations and also the behavior of self-complementary sequences. These direction cosines, together with the rotation angle about the space-fixed axis, form a set of three independent orientation variables of the bases that afford some advantages over the variously defined twist, roll, and tilt angles, either for static or average forms. An example for the static form of these variables is shown through their use to interpret crystal coordinates. An example for the average of orientation variables is based on statistical calculations. In this example, the orientation variables, together with the translational variables that describe the relative displacements of a pair of adjacent base pairs, form a canonically distributed ensemble in phase space spanned by these variables. Two sets of conformational variables are generated by using two different methods for performing rotation operations on the sequences of base pairs. The first method is based on the new single rotation about a space-fixed axis of rotation. This space-fixed axis of rotation is, in fact, the local helical axis as constructed previously by others. The second method is based on three consecutive rotations by Euler angles. Because of large flexibilities and anisotropies along various conformational variables of DNA base pairs, the two sets of generated conformational variables, based on these two different methods of performing rotation operations, lead to slightly different sets of structurally different, but energetically equivalent, spatial arrangements of the base pairs. PMID- 7787032 TI - Orientational dynamics of indane dione spin-labeled myosin heads in relaxed and contracting skeletal muscle fibers. AB - We have used electron paramagnetic resonance (EPR) spectroscopy to study the orientation and rotational motions of spin-labeled myosin heads during steady state relaxation and contraction of skinned rabbit psoas muscle fibers. Using an indane-dione spin label, we obtained EPR spectra corresponding specifically to probes attached to Cys 707 (SH1) on the catalytic domain of myosin heads. The probe is rigidly immobilized, so that it reports the global rotation of the myosin head, and the probe's principal axis is aligned almost parallel with the fiber axis in rigor, making it directly sensitive to axial rotation of the head. Numerical simulations of EPR spectra showed that the labeled heads are highly oriented in rigor, but in relaxation they have at least 90 degrees (Gaussian full width) of axial disorder, centered at an angle approximately equal to that in rigor. Spectra obtained in isometric contraction are fit quite well by assuming that 79 +/- 2% of the myosin heads are disordered as in relaxation, whereas the remaining 21 +/- 2% have the same orientation as in rigor. Computer-simulated spectra confirm that there is no significant population (> 5%) of heads having a distinct orientation substantially different (> 10 degrees) from that in rigor, and even the large disordered population of heads has a mean orientation that is similar to that in rigor. Because this spin label reports axial head rotations directly, these results suggest strongly that the catalytic domain of myosin does not undergo a transition between two distinct axial orientations during force generation. Saturation transfer EPR shows that the rotational disorder is dynamic on the microsecond time scale in both relaxation and contraction. These results are consistent with models of contraction involving 1) a transition from a dynamically disordered preforce state to an ordered (rigorlike) force-generating state and/or 2) domain movements within the myosin head that do not change the axial orientation of the SH1-containing catalytic domain relative to actin. PMID- 7787034 TI - Testing BR photocycle kinetics. AB - An improved K absorption spectrum in the visible is obtained from previous photocycle data for the D96N mutant of bacteriorhodopsin, and the previously obtained M absorption spectrum in the visible and the fraction cycling are confirmed at 25 degrees C. Data at lower temperatures are consistent with negligible temperature dependence in the spectra from 5 degrees C to 25 degrees C. Detailed analysis strongly indicates that there are two intermediates in addition to the first intermediate K and the last intermediate M. Assuming two of the intermediates have the same spectrum and using the L spectrum obtained previously, the best kinetic model with four intermediates that fits the time course of the intermediates is rather unusual, with two L's on a cul-de-sac. However, a previously proposed, more conventional model with five intermediates, including two L's with the same spectra and two M's with the same spectra, also fits the time course of the intermediates nearly as well. A new criterion that tests an individual proposed spectrum against data is also proposed. PMID- 7787035 TI - Deconvolution of C-phycocyanin beta-84 and beta-155 chromophore absorption and fluorescence spectra of cyanobacterium Mastigocladus laminosus. AB - Absorption and fluorescence spectra of the C-phycocyanin beta-subunit were quantitatively deconvoluted into component spectra of the beta-84 and beta-155 chromophores. The deconvolution procedure was based on a theoretical treatment of polarization properties. Four kinds of spectra (absorption, emission, emission polarization, and excitation polarization) measured on C-phycocyanin isolated from the cyanobacterium Mastigocladus laminosus were used as the experimental data set. Without any assumption of spectral shape, the absorption and fluorescence spectra of both chromophores were unambiguously resolved and their fluorescence quantum yields were evaluated. By combining the spectra of the alpha subunit, independently measured, with the resolved spectra of the beta-subunit, the fluorescence and fluorescence polarization spectra and the fluorescence quantum yield of the monomer were estimated; they agree with experimental values to within an acceptable error. Further, the matrix of energy transfer rates in the monomer was estimated; it gave a significantly different result (by up to 40%) from previously estimated ones. PMID- 7787036 TI - Rapid pH change due to bacteriorhodopsin measured with a tin-oxide electrode. AB - The photocurrent transient generated by bacteriorhodopsin (bR) on a tin-oxide electrode is due to pH change and not to charge displacement as previously assumed. Films of either randomly oriented or highly oriented purple membranes were deposited on transparent electrodes made of tin-oxide-coated glass. The membranes contained either wild-type or D96N-mutant bR. When excited with yellow light through the glass, the bR pumps protons across the membrane. The result is a rapid local pH change as well as a charge displacement. Experiments with these films show that it is the pH change rather than the displacement that produces the current transient. The calibration for the transient pH measurement is given. The sensitivity of a tin-oxide electrode to a transient pH change is very much larger than its sensitivity to a steady-state pH change. PMID- 7787037 TI - Relationship of proton release at the extracellular surface to deprotonation of the schiff base in the bacteriorhodopsin photocycle. AB - The surface potential of purple membranes and the release of protons during the bacteriorhodopsin photocycle have been studied with the covalently linked pH indicator dye, fluorescein. The titration of acidic lipids appears to cause the surface potential to be pH-dependent and causes other deviations from ideal behavior. If these anomalies are neglected, the appearance of protons can be followed by measuring the absorption change of fluorescein bound to various residues at the extracellular surface. Contrary to widely held assumption, the activation enthalpies of kinetic components, deuterium isotope effects in the time constants, and the consequences of the D85E, F208R, and D212N mutations demonstrate a lack of direct correlation between proton transfer from the buried retinal Schiff base to D85 and proton release at the surface. Depending on conditions and residue replacements, the proton release can occur at any time between the protonation of D85 and the recovery of the initial state. We conclude that once D85 is protonated the proton release at the extracellular protein surface is essentially independent of the chromophore reactions that follow. This finding is consistent with the recently suggested version of the alternating access mechanism of bacteriorhodopsin, in which the change of the accessibility of the Schiff base is to and away from D85 rather than to and away from the extracellular membrane surface. PMID- 7787039 TI - 13C multiplet nuclear magnetic resonance relaxation-derived ring puckering and backbone dynamics in proline-containing glycine-based peptides. AB - 13CH2-multiplet nuclear magnetic resonance relaxation studies on proline (P) containing glycine (G)-based peptides, GP, PG, GPG, PGG, and GPGG, provided numerous dipolar auto- and cross-correlation times for various motional model analyses of backbone and proline-ring bond rotations. Molecular dynamics simulations and bond rotation energy profiles were calculated to assess which motions could contribute most to observed relaxation phenomena. Results indicate that proline restricts backbone psi 1, psi 2, and phi 2 motions by 50% relative to those found for a polyglycine control peptide. psi 1 rotations are more restricted in the trans-proline isomer state than in the cis form. A two-state jump model best approximates proline ring puckering which in water could occur either by the C gamma endo-exo or by the C2 interconversion mechanism. The temperature dependence (5 degrees to 75 degrees C) of C beta, and C gamma, and C delta angular changes is rather flat, suggesting a near zero enthalpic contribution to the ring puckering process. In lower dielectric solvents, dimethylsulfoxide and methanol, which may mimic the hydrophobic environment within a protein, the endo-exo mechanism is preferred. PMID- 7787040 TI - Three-dimensional reconstruction of fibrin clot networks from stereoscopic intermediate voltage electron microscope images and analysis of branching. AB - Fibrin polymerizes to produce branching fibers forming a three-dimensional network, which has been difficult to visualize by conventional microscopy. Three dimensional images of whole clots at high resolution were obtained from stereo pair intermediate-voltage electron micrographs. Computer software was developed to produce three-dimensional reconstructions of the networks in the form of a pattern of links that connect branching junctions. Network parameters were measured and analyzed to characterize the clots quantitatively. Models in which all links were moved to the origin, while preserving their orientation, allowed visualization of some network parameters and facilitated comparison of networks. Fibrin clots formed in three different conditions were analyzed and compared by these methods. Clots formed in 0.20 M saline buffer consist of fibers of uniform size, and most of the branching junctions consist of three links. Fibrin clots formed in 0.05 M saline buffer are made up of very large diameter fiber bundles with far fewer branching junctions and correspondingly longer links. Clots formed in 0.40 M saline buffer consist of very fine fibers with numerous branching junctions and very short links. In summary, the extent of lateral aggregation is directly related to the distance between branching junctions and inversely related to the total number of branching junctions. These observations must be considered in defining possible mechanisms of fibrin branching. PMID- 7787038 TI - Protein sequence randomness and sequence/structure correlations. AB - We investigated protein sequence/structure correlation by constructing a space of protein sequences, based on methods developed previously for constructing a space of protein structures. The space is constructed by using a representation of the amino acids as vectors of 10 property factors that encode almost all of their physical properties. Each sequence is represented by a distribution of overlapping sequence fragments. A distance between any two sequences can be calculated. By attaching a weight to each factor, intersequence distances can be varied. We optimize the correlation between corresponding distances in the sequence and structure spaces. The optimal correlation between the sequence and structure spaces is significantly better than that which results from correlating randomly generated sequences, having the overall composition of the data base, with the structure space. However, sets of randomly generated sequences, each of which approximates the composition of the real sequence it replaces, produce correlations with the structure space that are as good as that observed for the actual protein sequences. A connection is proposed with previous studies of the protein folding code. It is shown that the most important property factors for the correlation of the sequence and structure spaces are related to helix/bend preference, side chain bulk, and beta-structure preference. PMID- 7787042 TI - Mesoscopic gel at low agarose concentration in water: a dynamic light scattering study. AB - Previous work in our laboratory has shown that at very low agarose concentration in water gelation still occurs within mutually disconnected, high concentration regions generated by spinodal demixing. The freely diffusing particles obtained in these conditions are studied in the present work by depolarized dynamic light scattering and probe diffusion experiments. These particles are found to behave as large (in fact, mesoscopic) polymer fibers entangled in a continuously rearranged mesh with scaling parameters typical of partially flexible, neutral chains. The present results allow specifying the notion of mesoscopic gelation. They also reveal that the same symmetry-breaking mechanism that allows macroscopic gelation at polymer concentrations well below the threshold for random cross-link percolation generates additional and unexpected phenomena. PMID- 7787043 TI - Fluorescence lifetime-based sensing in tissues: a computational study. AB - We have numerically solved the photon diffusion equation to predict the distribution of light in a tissue model system with a uniform concentration of fluorophore. Our results show that time-dependent measurements of light propagation can be used to monitor the fluorescent lifetimes of a uniformly distributed fluorophore in tissues. With proper referencing, frequency-domain measurements of phase-shift, theta, may allow quantitation of fluorescent lifetimes, tau, independent of changes in the local absorption and scattering properties. These results point to a new approach for noninvasive diagnostic monitoring through quantitation of fluorescent lifetime, tau, when the lifetime of the fluorophore is comparable with photon migration times. PMID- 7787041 TI - Diffusion and partitioning of proteins in charged agarose gels. AB - The effects of electrostatic interactions on the diffusion and equilibrium partitioning of fluorescein-labeled proteins in charged gels were examined using fluorescence recovery after photobleaching and gel chromatography, respectively. Measurements were made with BSA, ovalbumin, and lactalbumin in SP-Sepharose (6% sulfated agarose), in phosphate buffers at pH 7 and ionic strengths ranging from 0.01 to 1.0 M. Diffusivities in individual gel beads (D) and in the adjacent bulk solution (D infinity) were determined from the spatial Fourier transform of the digitized two-dimensional fluorescence recovery images. Equilibrium partition coefficients (phi) were measured by recirculating protein solutions through a gel chromatography column until equilibrium was reached, and using a mass balance. Diffusion in the gel beads was hindered noticeably, with D/D infinity = 0.4-0.5 in each case. There were no effects of ionic strength on BSA diffusivities, but with the smaller proteins (ovalbumin and lactalbumin) D infinity increased slightly and D decreased at the lowest ionic strength. In contrast to the modest changes in diffusivity, there were marked effects of ionic strength on the partition coefficients of these proteins. We conclude that for diffusion of globular proteins through gel membranes of like charge, electrostatic effects on the effective diffusivity (Deff = phi D) are likely to result primarily from variations in phi with only small contributions from the intramembrane diffusivity. PMID- 7787044 TI - Stark effect spectroscopy of tryptophan. AB - The change in permanent dipole moment (magnitude of delta mu) for the transition from the 1La state to the ground state of tryptophan is the key photophysical parameter for the interpretation of tryptophan fluorescence spectra in terms of static and dynamic dielectric properties of the surrounding medium. We report measurement of this parameter by means of electric field effect (Stark) spectroscopy for N-acetyl-L-tryptophanamide (NATA) in two solvents, the single tryptophan containing peptide melittin, and 5-methoxytryptophan. The values ranged from 5.9 to 6.2 +/- 0.4 Debye/f for NATA and melittin, where f represents the local field correction. The 1Lb magnitude of delta mu was much smaller. Application of Stark spectroscopy to these chromophores required decomposition of the near-UV absorption into the 1La and 1Lb bands by measurement of the fluorescence excitation anisotropy spectrum and represents an extension of the method to systems where band overlap would normally preclude quantitative analysis of the Stark spectrum. The results obtained for 5-methoxytryptophan point out limitations of this method of spectral decomposition. The relevance of these results to the interpretation of steady-state and time-resolved spectroscopy of tryptophan is discussed. PMID- 7787045 TI - Calculation of resonance energy transfer in crowded biological membranes. AB - Analytical and numerical models were developed to describe fluorescence resonance energy transfer (RET) in crowded biological membranes. It was assumed that fluorescent donors were linked to membrane proteins and that acceptors were linked to membrane lipids. No restrictions were placed on the location of the donor within the protein or the partitioning of acceptors between the two leaflets of the bilayer; however, acceptors were excluded from the area occupied by proteins. Analytical equations were derived that give the average quantum yield of a donor at low protein concentrations. Monte Carlo simulations were used to generate protein and lipid distributions that were linked numerically with RET equations to determine the average quantum yield and the distribution of donor fluorescence lifetimes at high protein concentrations, up to 50% area fraction. The Monte Carlo results show such crowding always reduces the quantum yield, probably because crowding increases acceptor concentrations near donor-bearing proteins; the magnitude of the reduction increases monotonically with protein concentration. The Monte Carlo results also show that the distribution of fluorescence lifetimes can differ markedly, even for systems possessing the same average lifetime. The dependence of energy transfer on acceptor concentration, protein radius, donor position within the protein, and the fraction of acceptors in each leaflet was also examined. The model and results are directly applicable to the analysis of RET data obtained from biological membranes; their application should result in a more complete and accurate determination of the structures of membrane components. PMID- 7787046 TI - Atomic force microscopy of the myosin molecule. AB - Atomic force microscopy (AFM) has been used to study the structure of rabbit skeletal muscle myosin deposited onto a mica substrate from glycerol solution. Images of the myosin molecule have been obtained using contact mode AFM with the sample immersed in propanol. The molecules have two heads at one end of a long tail and have an appearance similar to those prepared by glycerol deposition techniques for electron microscopy, except that the separation of the two heads is not so well defined. The average length of the tail (155 +/- 5 nm) agrees well with previous studies. Bends in the myosin tail have been observed at locations similar to those observed in the electron microscope. By raising the applied force, it has been possible locally to separate the two strands of the alpha helical coiled-coil tail. We conclude that the glycerol-mica technique is a useful tool for the preparation of fibrous proteins for examination by scanning probe microscopy. PMID- 7787048 TI - A class of parametrically excited calcium oscillation detectors. AB - Intracellular Ca2+ oscillations are often a response to external signals such as hormones. Changes in the external signal can alter the frequency, amplitude, or form of the oscillations suggesting that information is encoded in the pattern of Ca2+ oscillations. How might a cell decode this signal? We show that an excitable system whose kinetic parameters are modulated by the Ca2+ concentration can function as a Ca2+ oscillation detector. Such systems have the following properties: (1) They are more sensitive to an oscillatory than to a steady Ca2+ signal. (2) Their response is largely independent of the signal amplitude. (3) They can extract information from a noisy signal. (4) Unlike other frequency sensitive detectors, they have a flat frequency response. These properties make a Ca(2+)-sensitive excitable system nearly ideal for detecting and decoding Ca2+ oscillations. We suggest that Ca2+ oscillations, in concert with these detectors, can act as cellular timekeepers to coordinate related biochemical reactions and enhance their overall efficiency. PMID- 7787049 TI - "Surface tensions" in the lung. PMID- 7787047 TI - Design and performance of an ultraviolet resonance Raman spectrometer for proteins and nucleic acids. AB - We describe an ultraviolet resonance Raman (UVRR) spectrometer appropriate for structural studies of biological macromolecules and their assemblies. Instrument design includes the following features: a continuous wave, intracavity doubled, ultraviolet laser source for excitation of the Raman spectrum; a rotating cell (or jet source) for presentation of the sample to the laser beam; a Cassegrain optic with f/1.0 aperture for collection of the Raman scattering; a quartz prism dispersing element for rejection of stray light and Rayleigh scattering; a 0.75-m single grating monochromator for dispersion of the Raman scattering; and a liquid nitrogen-cooled, charge-coupled device for detection of the Raman photons. The performance of this instrument, assessed on the basis of the observed signal-to noise ratios, the apparent resolution of closely spaced spectral bands, and the wide spectrometer bandpass of 2200 cm-1, is believed superior to previously described UVRR spectrometers of similar design. Performance characteristics of the instrument are demonstrated in UVRR spectra obtained from standard solvents, p-ethylphenol, which serves as a model for the tyrosine side chain, the DNA nucleotide deoxyguanosine-5'-monophosphate, and the human tumor necrosis factor binding protein, which is considered representative of soluble globular proteins. PMID- 7787050 TI - 7th Biophysical Discussions. Molecular motors: structure, mechanics and energy transduction. Proceedings of a meeting. PMID- 7787051 TI - Distinct molecular processes associated with isometric force generation and rapid tension recovery after quick release. AB - It was proposed by Huxley and Simmons (Nature 1971, 233:533-538) that force generating cross-bridges are attached to actin in several stable positions. In this concept, isometric force is generated by the same mechanism as the quick tension recovery after an abrupt release of length; i.e., when crossbridges proceed from the first postulated stable position to the second and/or subsequent positions, resulting in straining of the elastic elements within the cross bridges. Therefore, isometric force is generated by cross-bridges in the second or even subsequent stable positions. However, through mechanical measurements of skinned rabbit psoas muscle fibers, we found that during isometric contraction only the first stable state is significantly occupied; i.e., isometric force is generated by cross-bridges in the first of the stable states. Thus, isometric force and the quick tension recovery appear to result from two distinctly different molecular processes. We propose that isometric force results from a structural change in the actomyosin complex associated with the transition from a weakly bound configuration to a strongly bound configuration before the reaction steps in the Huxley-Simmons model, whereas a major component of quick tension recovery originates from transitions among the subsequent strongly bound states. Mechanical, biochemical, and structural evidence for the two distinct processes is summarized and reviewed. PMID- 7787052 TI - Function of the N terminus of the myosin essential light chain of vertebrate striated muscle. AB - All but one (LC3-f; a fast skeletal muscle isoform) of the essential light chain isoforms of myosin (ELC) that are expressed in vertebrate striated muscles have an extended N terminus that is found neither in invertebrate ELCs nor in the majority of vertebrate smooth and nonmuscle myosin ELCs. Studies with permeabilized skeletal muscle fibers and in vitro motility assays have demonstrated that the presence of the ELC isoform lacking the N-terminal extension (LC3-f) is correlated with an increased maximal velocity of filament sliding. To examine further this modulatory role of the ELCs, a procedure was developed for the exchange of ELCs that is based on a technique for the removal of regulatory light chains from permeabilized muscle fibers. Different isoforms of the ELCs and mutant ELCs were exchanged into permeabilized skeletal muscle fibers from rabbit psoas muscle. The role of the ELCs of myosin in altering the shortening Vmax of striated muscle was confirmed. Additionally, experiments with mutant ELCs in which lysines at the extreme N terminus were replaced with alanines, demonstrated an increased shortening Vmax that coincided with removal of the positive charges contributed by the lysines. This suggests that charge interactions (i.e., salt bridges) between the N terminus of the ELC and negatively charged amino acids on the surface of actin cause a slowing of filament sliding. Whether this role in altering shortening velocity is the primary function of the extended N terminus of the ELC or whether it is merely a consequence of providing a tether between the thick and thin filaments is discussed. PMID- 7787053 TI - Structural studies on the ribbon-to-helix transition in profilin: actin crystals. AB - Knowledge of the structure of actin in its various conformational states is important for understanding the diverse motile activities carried out by eukaryotic cells. Profilin:actin crystals provide a unique system for studying conformational states of actin, because they exhibit a high degree of polymorphism in response to environmental conditions while maintaining crystalline order. A preliminary comparison of two states of profilin:beta-actin crystals shows that crystal polymorphism involves movements of actin subdomains at hinge points homologous to those found in hexokinase, a protein whose polypeptide fold is related to actin. The homology of the hinge points in actin to those in hexokinase suggests that actin subdomain movements in profilin:beta actin crystals have functional significance. We discuss how these movements could be related to structural transitions between states of filamentous actin in muscle contraction. PMID- 7787054 TI - Role of skeletal and smooth muscle myosin light chains. AB - A persistent problem with the rotating cross-bridge model for muscle contraction has been the inability to detect any large conformational changes within the myosin molecule to account for a working stroke of 5-10 nm. The recent crystal structure of myosin subfragment-1 suggests a solution to this problem by showing the presence of two distinct domains: a catalytic or motor domain, from which extends a long, 8.5-nm alpha-helix that is stabilized by the regulatory and essential light chains. Rayment et al. (1993) proposed that closure of a cleft in the motor domain could rotate the light chain-binding domain by a sufficient distance to account for the power stroke. With the development of new in vitro motility assays, and the ability to prepare unusual myosins by biochemical and molecular biological methods, we can now examine this hypothesis and explore the role of the light chains in generating force and movement. Here we will review some of these recent data and outline a possible mechanism for how light chains regulate contractile properties. PMID- 7787055 TI - A novel electron paramagnetic resonance spin label and its application to study the cross-bridge cycle. AB - We have used a novel alpha-iodoketone spin-label (IKSL) to study myosin head orientation and cross-bridge dynamics in the putative pre-powerstroke state. Possible perturbation of the cross-bridge cycle by the label was assayed by the sinusoidal analysis method (Kawai and Brandt, 1980; Kawai and Zhao, 1993), which determines the rate constants of the elementary steps in the cycle. A comparison of the rates obtained from unlabeled and IKSL fibers revealed small (10-20%) changes in the ATP hydrolysis rate and in the rate constants of the elementary steps. The labeling induced small changes (< 13%) in the distribution of the cross-bridges among the various intermediate states. Pre-powerstroke cross bridges were induced by aluminum fluoride in the presence of Ca2+ and ATP. In this state, force development is inhibited, but a large proportion (40%) of the cross-bridges are still attached to the thin filament. We have used conventional electron paramagnetic resonance to measure orientation, and have found that the pre-powerstroke heads are as disordered as in relaxation. Their mobility, as determined by saturation transfer electron paramagnetic resonance, was significantly restricted. Assuming that stiffness is proportional to the fraction of strongly attached heads, the rotational correlation time of the bound heads is estimated to be tau r = approximately 150-400 microseconds. PMID- 7787057 TI - The conformation of the active site of myosin probed using mant-nucleotides. AB - Changes in the conformation of the active site of myosin subfragment-1 (S1) may be linked to the production of force during the powerstroke. We probed the conformation of the nucleotide pocket by measuring the solvent accessibility of bound mant-nucleotides. Solvent accessibility was determined by measuring the quenching of fluorescence produced by the solvent phase quencher acrylamide. The fluorescent mant moiety is attached to the ribose and is located near the outside of the pocket where it is likely to be sensitive to opening of the pocket. MantADP was highly protected from the quencher when bound to the active site of S1. A similar degree of protection was also observed for mantATP during steady state hydrolysis by S1, and for mantADP bound to acto-S1 or to myosin in myofibrils. Assuming that S1-mantATP and actoS1-mantADP represent states at the beginning and the end of the powerstroke, respectively, we conclude that the myosin nucleotide pocket does not undergo a large conformational change during the powerstroke. However, the high degree of protection seen for mant-nucleotides is not easily explained by the open structure of the nucleotide pocket in the S1 nucleotide complex observed by x-ray diffraction. PMID- 7787059 TI - Purification of kinesin-related protein complexes from eggs and embryos. AB - We have developed a biochemical screen for the identification of kinesin-related proteins (KRPs) in their natural host cells and the subsequent purification of these KRPs as native, functional multimeric complexes. The screen involves immunoblotting with pan-kinesin peptide antibodies that recognize several presumptive KRPs in cytosolic extracts; the antibodies have been used so far to monitor the purification of two bona fide kinesin-related motor protein complexes. These two KRPs were purified via AMPPNP-induced microtubule affinity binding, ATP-induced elution from AMPPNP microtubules, gel filtration fractionation, and sucrose density gradient centrifugation. KRP(85/95) from sea urchin (Strongylocentrotus purpuratus) eggs behaves as a heterotrimeric complex of 85-, 95-, and 115-kDa subunits that moves toward the plus ends of microtubule tracks at approximately 0.4 micron/s. KRP(130) from fruitfly (Drosophila melanogaster) embryos behaves as a homotetrameric complex of four 130-kDa subunits that moves toward the plus ends of microtubule tracks at approximately 0.04 micron/s. To our knowledge, KRP(85/95) and KRP(130) are the only KRPs to have been purified from native tissue as functional multimeric motor complexes. PMID- 7787056 TI - The mechanism of force generation in myosin: a disorder-to-order transition, coupled to internal structural changes. AB - We propose a molecular mechanism of force generation in muscle, based primarily on site-specific spectroscopic probe studies of myosin heads in contracting muscle fibers and myofibrils. Electron paramagnetic resonance (EPR) and time resolved phosphorescence anisotropy (TPA) of probes attached to SH1 (Cys 707, in the catalytic domain of the head) have consistently shown that most myosin heads in contracting muscle are dynamically disordered, undergoing large-amplitude rotations in the microsecond time range. Some of these disordered heads are bound to actin, especially in the early (weak-binding, preforce) phase of the ATPase cycle. The small ordered population (10-20%) is rigidly oriented precisely as in rigor, with no other distinct angle observed in contraction or in the presence of intermediate states trapped by nucleotide analogs. These results are not consistent with the classical model in which the entire head undergoes a 45 degree transition between two distinct orientations. Therefore, it has been proposed that the catalytic domain of the myosin head has only one stereospecific (rigor-like) actin-binding angle, and that the head's internal structure changes during force generation, causing the distal light-chain-binding domain to rotate. To test this model, we have performed EPR and TPA studies of probes attached to regulatory light chains (RLCs) in rabbit and scallop myofibrils and fibers. The RLC results confirm the predominance of dynamic (microsecond) rotational disorder in both relaxation and contraction, and show that the different mechanisms of calcium regulation in the two muscles produce different rotational dynamics. In rabbit myofibrils, RLC probes are more dynamically disordered than SH1 probes, especially in rigor and contraction,indicating that the light-chain-binding domain undergoes rotational motions relative to the catalytic domain when myosin heads interact with actin. An SH1-bound spin label, which is sensitive to myosin's internal dynamics, resolves three distinct conformations during contraction, and time-resolved EPR shows that these transitions are coupled to specific steps in the ATPase cycle. We propose that force is generated during contraction by a disorder-to-order transition, in which myosin heads first attach weakly to actin in a nonstereospecific mode characterized by large-scale dynamic disorder, then undergo at least two conformational transitions involving large scale structural (rotational) changes within the head, culminating in a highly ordered strong-binding state that bears force. PMID- 7787060 TI - Torque generation by the flagellar rotary motor. AB - A review is given of the structure and dynamics of the flagellar rotary motor. Force-generating elements in a motor driving a tethered bacterium (a cell fixed to the substratum by a single flagellum) exert forces of order 20 pN while moving at speeds of order 1 micron/s. Force-generating elements in a motor driving a flagellar filament in a bundle exert forces some 10-fold lower but move at speeds more than 10-fold higher. The motor torque-speed relationship has been measured over a wide dynamic range. Motors strongly resist being driven backwards and are easily broken. PMID- 7787062 TI - Pathway of the microtubule-kinesin ATPase. AB - We have established pathway of the kinesin ATPase by direct measurement of each step in the pathway. Kinesin binds to microtubules with an 8-nm repeat and a stoichiometry of one kinesin monomer unit per tubulin dimer. Thus, the dimeric kinesin binds with both heads attached to the microtubule and on adjacent tubulin subunits. In the steady state, kinesin has a low ATPase activity that is limited by the rate of ADP release (< 0.01 s-1) in the absence of microtubules and is activated 2000-fold by the addition of microtubules to achieve a maximum rate of approximately 20 s-1. Transient-state kinetic analysis has provided direct measurement of individual steps of the reaction to define the pathway of the microtubule-kinesin ATPase. These studies establish that the rate-limiting step in the ATPase pathway is the release of the kinesin-product complex (K.ADP.P) from the microtubule following ATP hydrolysis. After phosphate release, the rebinding of kinesin-ADP to the microtubule is fast, accounting for the high activation of the ATPase at low microtubule concentration. This ATPase cycle explains the phenomenological differences between myosin and kinesin observed in motility assays. Kinesin remains associated with a microtubule through multiple rounds of hydrolysis, because it spends only a small fraction of its duty cycle in the dissociated state. The discussion of this paper will focus on the new data, their interpretation, and significance for mechanisms of force production. The ATPase coupling mechanism will be compared with dynein and myosin. PMID- 7787058 TI - Molecular genetic analysis of myoF, a new Dictyostelium myosin I gene. AB - Several new members of the Dictyostelium myosin family have been identified by physical mapping techniques in combination with PCR. Here we describe the initial molecular genetic characterization of one of these, myoF. A 1-kb segment of the myoF gene was obtained by the PCR and used as a specific probe for Northern analysis and as a vehicle for gene-targeting studies. The myoF gene is expressed as a 3.7-kb message, a size consistent with it encoding a myosin I class unconventional myosin, bringing the total of myosin is present in Dictyostelium to six. Analysis of strains in which the myoF gene has been disrupted reveals that loss of the myoF protein does not result in obvious defects either in cellular translocation, or in other readily assayed actin-based processes. The results of our investigation indicate that the myosin I family is quite large in Dictyostelium, and that several members, including myoF, may either be functionally redundant or play roles in as yet undescribed actin-based processes. PMID- 7787061 TI - Conserved machinery of the bacterial flagellar motor. AB - Novel periplasmic and cytoplasmic structural modules of the bases of bacterial flagella have been observed in situ and isolated using new biochemical protocols. Flagellar rotation may depend upon interactions of these modules with the intramembrane particle rings, a ubiquitous feature of flagellar bases necessary for torque generation. The outer membrane-associated basal disk of the Wolinella succinogenes polar flagellum has architecture well suited for interaction with the ring particles. However, antibody against the main W. succinogenes basal disk protein did not cross-react with flagella-enriched fractions from Salmonella typhimurium and Bacillus firmus; nor have such structures been observed in these species thus far. Antibodies against two S. typhimurium proteins, FliG and FliM, known to be involved in motor function and part of the cytoplasmic module in this species cross-reacted with flagella-enriched fractions from both W. succinogenes and B. firmus. In addition, flagellar cytoplasmic structure could be isolated from B. firmus. The basal disk may anchor the flagellar motor to the cell wall in some polar bacteria, but this does not seem to be a unique strategy. In contrast, the data indicate that the cytoplasmic module is conserved. PMID- 7787063 TI - Helicase-catalyzed DNA unwinding: energy coupling by DNA motor proteins. AB - DNA helicases catalyze the unwinding of double-stranded (ds) DNA to yield the single-stranded (ss) DNA intermediates required in DNA replication, recombination, and repair. DNA helicases couple the free energy of nucleoside triphosphate (NTP) binding and hydrolysis to separate the two complementary DNA strands while also translocating vectorially along the DNA substrate. As such, helicases are functionally DNA motor proteins. The functional form of helicases generally appears to be oligomeric (usually dimers or hexamers), which provides the helicase with multiple DNA binding sites that are required for translocation and DNA unwinding. The affinity of ss- versus dsDNA for these multiple DNA binding sites is modulated allosterically by NTP binding, hydrolysis, and product release, which is central to helicase-catalyzed DNA unwinding. The mechanistic details of the DNA unwinding, translocation, and NTPase reactions are only starting to emerge. We discuss energy coupling by DNA helicases in general, and by the dimeric E. coli Rep helicase in particular, focusing on the similarities of these enzymes to classical motor proteins. PMID- 7787064 TI - Nucleotide binding studies of bacteriophage T7 DNA helicase-primase protein. AB - Bacteriophage T7 DNA helicase protein is a hexameric protein that contains identical subunits arranged in a ring-like structure. Single-stranded DNA binds through the hole of the ring, and the helicase protein translocates and unwinds duplex DNA using nucleoside triphosphate (NTP) hydrolysis. In our efforts to understand how NTP hydrolysis may be coupled to movement of the helicase on the DNA, we have quantitated the equilibrium binding of deoxythymidine triphosphate and thymidine 5'-(beta,gamma-methylenetriphosphate) using nitrocellulose binding assays. Even though the helicase consists of six identical subunits, each hexamer was found to bind only three NTP molecules. These results indicate half-site binding or negative cooperativity in NTP binding by the hexamer. Interestingly, binding of three NTP molecules to the hexamer was sufficient for stoichiometric binding of a single-stranded oligodeoxynucleotide. Similar negative cooperativity in NTP binding has also been observed for other helicases, suggesting that it may be a general feature of hexameric helicases. The significance of half-site binding, however, is not understood at the present time. PMID- 7787066 TI - A new method for the time-resolved measurement of phosphate release in permeabilized muscle fibers. AB - A new method for the measurement of phosphate release in contracting and relaxed permeabilized muscle fibers is described. The assay is based on a genetically engineered phosphate-binding protein labeled with a coumarin fluorescent probe, which binds inorganic phosphate tightly and shows a fourfold increase in fluorescence upon binding. Measurements of Pi release on the millisecond time scale with sensitivity in the 10 microM range are obtained that provide new information about the relationship between ATP hydrolysis and force production. PMID- 7787065 TI - Structural studies of myosin:nucleotide complexes: a revised model for the molecular basis of muscle contraction. AB - The structures of the MgADP-beryllium fluoride and MgADP-aluminum fluoride complexes of the truncated myosin head from Dictyostelium myosin II are reported. These reveal the location of the nucleotide complex and define the amino acid residues that form the active site. The tertiary structure of the beryllium fluoride complex is essentially identical to that seen previously in the three dimensional structure of chicken skeletal muscle myosin. By contrast, significant domain movements are observed in the aluminum fluoride complex. These structural findings form the basis of a revised model for the structural basis of the contractile cycle. It is now suggested that the narrow cleft that splits the central 50-kDa segment of the heavy chain provides not only the communication route between the nucleotide-binding pocket and actin but also transmits the conformational change necessary for movement. PMID- 7787068 TI - The actomyosin interaction and its control by tropomyosin. PMID- 7787067 TI - The role of three-state docking of myosin S1 with actin in force generation. AB - It has been shown that in solution myosin subfragment 1 binds to actin in three principal steps: [formula: see text] The nucleotide bound to myosin has a major influence on the equilibrium constant of the third of these steps but little effect on the other two. The third step is thought to be coupled to the force generating event. Three-step binding and structure: The formation of the collision complex is strongly ionic strength dependent but independent of temperature. The isomerization to the A state is not strongly dependent on ionic strength but is affected by organic solvent and temperature. In contrast the isomerization to the R state-is affected by both ionic strength and organic solvent but little affected by temperature. The recent docking of the three dimensional structures of actin and S1 suggest possible structural correlates of these events. These studies lead to predictions for the docking process, which may be tested using site-directed mutagenesis or peptide inhibitors. Three-step binding and head-head interactions: Studies of HMM binding to actin compared with S1 binding show that binding of two heads in the A state are unlikely presumably because of strain effects. However, binding of two heads as one A and one R state shows little evidence of strain while the isomerization of the second head to give two R states is fivefold weaker than for an isolated S1 head. These results suggest that in a rapidly shortening muscle only one head is likely to be attached at a time. Under isometric conditions, although it is possible for both heads to bind to adjacent actins, it is unlikely that both will be in the force holding R state simultaneously. Three-step binding and regulation by tropomyosin troponin:Our recent solution studies have established that the thin filament can exist in three calcium-dependent states which we termed blocked, closed and open. A blocked state cannot form the A state with S1 and a closed state cannot form the force holding R state nor accelerate product release from S1. Thus control operates at two distinct points in the docking process. The docking process itself is coupled to hydrolysis of ATP (the A-to-R isomerization is inhibited by the presence of the gamma Pi on ATP), and therefore all of these events are interrelated.The coming together of these different strands provides a biochemical framework that should allow the dynamic properties of the crossbridge in muscle to be understood. PMID- 7787069 TI - Coordinated hydrolysis explains the mechanical behavior of kinesin. AB - The two-headed motor protein kinesin hydrolyzes nucleotide to move unidirectionally along its microtubule track at speeds up to 1000 nm/s (Saxton et al., 1988) and develops forces in excess of 5 pN (Hunt et al., 1994; Svoboda et al., 1994a). Individual kinesin molecules have been studied recently in vitro, and their behavior has been characterized in terms of force-velocity curves and variance measurements (Svoboda and Block, 1994a; Svoboda et al., 1994b). We present a model for force generation in kinesin in which the ATP hydrolysis reactions are coordinated with the relative positions of the two heads. The model explains the experimental data and permits us to study the relative roles of Brownian motion and elastic deformation in the motor mechanism of kinesin. PMID- 7787070 TI - Can membrane proteins drive a cell? PMID- 7787071 TI - A three-line muscle cross-bridge cycle with strain-dependent ligand releases. PMID- 7787072 TI - Nucleotide-binding site of the myosin head is under the influence of thin filament proteins. PMID- 7787073 TI - The myofibril as a model for muscle fiber ATPase. PMID- 7787074 TI - Comparison between tension transients during isometric contraction and in rigor in isolated fibers from frog skeletal muscle. PMID- 7787075 TI - Mechanochemical coupling of molecular motors to ATP hydrolysis. PMID- 7787076 TI - Ciliary beat frequency is controlled by a dynein light chain phosphorylation. AB - cAMP-dependent phosphorylation of a 29-kDa axonemal polypeptide (p29) increases the swimming speed of permeabilized Paramecium and in vitro translocation velocity of bovine brain microtubules over 22S dynein extracted from Paramecium axonemes. A quantitative relationship between microtubule translocation velocity and beat frequency is developed. We conclude that p29 acts as a regulatory light chain of outer arm dynein in the control of ciliary beat frequency. PMID- 7787077 TI - The contributions of light chains to myosin function. PMID- 7787078 TI - Myosin regulatory light chain phosphorylation and the production of functionally significant changes in myosin head arrangement on striated muscle thick filaments. PMID- 7787079 TI - Characterization of myosin II isoforms containing insertions of amino acids in the flexible loop near the ATP-binding pocket. PMID- 7787080 TI - Differential phosphorylation in vivo of cytoplasmic dynein in anterograde and whole cell compartments. PMID- 7787082 TI - Two heads are required for phosphorylation-dependent regulation of smooth muscle myosin. PMID- 7787081 TI - Essential myosin light chain isoforms and energy transduction in skeletal muscle fibers. PMID- 7787084 TI - Measurement of the isometric force exerted by a single kinesin molecule. PMID- 7787083 TI - Analysis of high resolution recordings of motor movement. AB - The development of in vitro motility assays for motor proteins has been accompanied by a parallel development of advanced optical instrumentation capable of recording motion at the molecular level. Devices now exist that can record displacements to better than 0.1 nm at bandwidths in excess of 10 kHz, and that can place controlled forces up to many pN on single motors. Ultra-high resolution data from experiments are now pouring in. The analysis and subsequent interpretation of experimental records, which are inevitably contaminated with high levels of thermal noise, remain an ongoing challenge. This essay examines selected issues relating to this challenge and discusses some alternative approaches. PMID- 7787085 TI - The mechanics of force generation by kinesin. AB - Several laboratories have developed highly sensitive mechanical techniques for studying the movement of purified motor proteins along their associated filaments. The aim of these experiments is to test models for force generation, such as the powerstroke model and "ratchet" or diffusional models, by 1) directly visualizing the path on the filament along which the motor moves, 2) measuring the force exerted by the motor against the filament, and 3) characterizing the passive mechanical properties (elasticity) of the motor. This paper focuses on recently published work on the microtubule-based motor kinesin taking this mechanical approach. Related work on myosin is mentioned for comparison. PMID- 7787086 TI - Smooth muscle myosin: a high force-generating molecular motor. AB - Smooth muscle generates as much force per cross sectional area of muscle as skeletal muscle with only one-fifth the myosin content. Although this apparent difference could be explained at the tissue or cellular level, it is possible that at the molecular level smooth muscle cross-bridges generate greater average force than skeletal muscle cross-bridges. To test this hypothesis, we used an in vitro motility assay (VanBuren et al., 1994) in which either chicken thiophosphorylated gizzard smooth or pectoralis skeletal muscle monomeric myosin is adhered to a nitrocellulose surface. A fluorescently labeled actin filament, attached to an ultracompliant (50-200 nm/pN) glass microneedle, is brought in contact with the myosin surface. Isometric force, being generated by myosin cross bridges pulling on the attached actin filament, is calculated from the extent to which the calibrated microneedle is deflected. By measuring the density of myosin adhered to the surface, we estimated the number of myosin cross-bridges that are able to interact with a length of actin filament in contact with the myosin surface. In a direct comparison between smooth and skeletal muscle myosin, the average force per cross-bridge was 0.8 and 0.2 pN, respectively. Surprisingly, smooth muscle myosin generates approximately 4 times greater average force per cross-bridge head than skeletal muscle myosin. Because average isometric force is the product of the cross-bridge unitary force and duty cycle, we are presently using a laser optical trap in an attempt to measure unitary events from single myosin molecules. This approach should allow us to determine whether an increase in unitary force, duty cycle, or both contribute to smooth muscle myosin's enhanced force-generating capacity compared with skeletal muscle myosin. PMID- 7787088 TI - Implications of diffusion-controlled limit for processivity of dimeric kinesin head domains. AB - The diffusion-limited rate for association of the ADP complex of dimeric DKH392 kinesin head domains with a microtubule was estimated to be 2-3 x 10(7) M-1 s-1 based on approximation of a microtubule as a highly elongated prolate ellipsoidal adsorber of 100% efficiency. This theoretical bimolecular rate is approximately 100-fold smaller than the experimental rate, kcat/KMT0.5, for DKH392 that was determined from the stimulation of the steady-state ATPase rate by microtubules. The large difference between these two estimates of the bimolecular rate indicates that it is likely that dimeric DKH392 hydrolyzes multiple ATP molecules during each diffusional encounter with a microtubule. PMID- 7787087 TI - Structural features involved in force generation in the kinesin superfamily. AB - In this article, I discuss our current understanding of the structural features of the microtubule-dependent motor kinesin and its relatives, which are needed for force generation. It has become clear that the motor domain itself is likely to be only about 340 amino acids, and that direction of movement is also controlled within this region. There is reason, however, to be suspicious that elements in the tail that are located immediately adjacent to the motor region influence, or in some way contribute to, normal motor activity. Finally, I describe recent work designed to identify the regions involved in the kinesin microtubule interaction. PMID- 7787089 TI - Determinants of motor polarity in the kinesin proteins. AB - Many of the proteins that are members of the kinesin family of microtubule motor proteins are plus-end motors; however, a few of the kinesin proteins have now been found to be minus-end microtubule motors. Overall structural features of the proteins can be used to identify further kinesins that are likely to be minus-end motors. Structural or biochemical differences that may serve as the basis of the "reversed" polarity of a unique subset of the kinesin proteins are discussed. PMID- 7787090 TI - Structural and functional features of one- and two-headed biotinated kinesin derivatives. AB - The oligomeric structure was determined for four recombinant kinesin derivatives containing N-terminal fragments of the kinesin alpha-subunit. Some of the proteins were dimeric (two-headed) molecules with mechanochemical properties similar to those of intact kinesin. Comparison of the primary and quaternary structures of the derivatives with those of intact kinesin suggests that structures distinct from the long alpha-helical coiled-coil rod domain contribute to subunit self-association. Three of the proteins contain a single engineered site for post-translational biotination in vivo; this facilitates analysis of motility in experiments in which the proteins are specifically bound to streptavidin-conjugated microscopic plastic beads. One of the derivatives is monomeric (one-headed); like the two-headed derivatives, it is functional in the motility assay and is a microtubule-dependent ATPase. Unlike intact kinesin and the two-headed derivatives, the one-headed enzyme fails to track microtubule protofilaments. This confirms a prediction of proposed "hand-over-hand" mechanisms of kinesin movement. The ability of molecules with a one-headed solution structure to generate movement is consistent with a translocation generating conformational change internal to the kinesin head. A simple set of coupling rules can be used to formulate consistent mechano-chemical mechanisms that explain movement by both one- and two-headed kinesin molecules. PMID- 7787091 TI - Cargo-activated ATPase activity of kinesin. AB - We have measured the ATPase activity of squid optic lobe kinesin bound to polystyrene beads in the presence of microtubules. We find that there is a substantial increase (> 10-fold) in the microtubule-activated ATPase activity for bead-bound kinesin over free kinesin. We tentatively attribute such cargo activated ATPase activity to the presence of a self-inhibited form of kinesin in solution, which becomes activated when bound to a bead in the presence of alpha casein. Further experiments are underway to unravel this phenomenon and, in addition, to associate the traveling distance of beads with the observed ATPase rate to determine the average number of ATP consumed per kinesin-bead per micron of travel along microtubule. PMID- 7787092 TI - Mechanical measurements of single actomyosin motor force. AB - To elucidate the mechanism of force generation by actomyosin motor, a measuring system was constructed, in which an in vitro motility assay was combined with an optical trapping technique. An actin filament of several micron long was attached to a gelsolin-coated polystyrene bead, and was allowed to interact with a small number (approximately 1/1 micron actin filament) of rabbit skeletal heavy meromyosin (an active subfragment of myosin) molecules bound to a nitrocellulose coated coverglass. The bead position was determined at 33-ms intervals. We measured the force generation event at relatively low (100-400 nM) ATP concentration so that the occurrence of individual force generation events could be detected with our time resolution. The actin-bound bead held in the optical trap moved in a stepwise manner in the direction of the actin filament only in the presence of ATP. At the trap strength of 0.3 pN/nm, the maximum size of the step was 11 nm, and the maximum force associated with the movement was 3.3 pN. PMID- 7787093 TI - Conformational changes of the myosin heads during hydrolysis of ATP as analyzed by x-ray solution scattering. AB - We have shown for the first time that the myosin head (subfragment-1, S1), the energy-transducing component in the actomyosin motor system undergoes a distinct shape change during hydrolysis of ATP using x-ray solution scattering techniques. Among various analogs for intermediate states of the S1 ATPase cycle, the complexes with MgADP and vanadate (S1.ADP.Vi), MgADP and beryllium fluoride (S1.ADP.BeF3), or MgADP and aluminum fluoride (S1.ADP.AIF4) showed a shape change similar to that in the presence of MgATP, but the complexes with ATP gamma S (S1.ADP gamma S) and MgADP trapped by cross-linking with pPDM (S1.ADP-pPDM) seemed to have a shape similar to that of nucleotide-free S1. These results indicate that the shape of an S1**.ADP.Pi state is more rounded or bent than in other intermediate states of the S1 ATPase cycle. Such changes occur in light chain 2-deficient S1 and also in smooth muscle S1. However, MgADP-fluoride complexes with smooth muscle S1 (without phosphorylation of a regulatory light chain) seemed to have a structure similar to that of nucleotide-free S1. Analysis of x-ray scattering data indicated that a conformational change of S1 in the presence of MgATP might be caused by a hinge-like bending movement between the catalytic and regulatory domains. The global change of S1 is correlated with some specific changes of a nucleotide-binding moiety. PMID- 7787094 TI - Characterization of single actin-myosin interactions. AB - The feedback-enhanced laser trap assay (Finer et al., 1994) allows the measurement of force and displacement produced by single myosin molecules interacting with an actin filament suspended in solution by two laser traps. The average displacement of 11 nm at low load and the average force of 4 pN near isometric conditions are consistent with the conventional swinging cross-bridge model of muscle contraction (Huxley, 1969). The durations of single actin-myosin interactions at low load, 3-7 ms, suggest a relatively small duty ratio. Event durations can be increased either by reducing the ATP concentration until ATP binding is rate-limiting or by lowering the temperature. For sufficiently long interactions near isometric conditions, low frequency force fluctuations were observed within the time frame of a single event. Single myosin events can be measured at ionic strengths that disrupt weak binding actomyosin interactions, supporting the postulate of distinct weak and strong binding states. Myosin generated force and displacement were measured simultaneously against several different loads to generate a force-displacement curve. The linear appearance of this curve suggests that the myosin powerstroke is driven by the release of a strained linear elastic element with a stiffness of approximately 0.4 pN nm-1. PMID- 7787097 TI - Forces and steps generated by single myosin molecules. PMID- 7787096 TI - Are actin filaments moving under unloaded conditions in the in vitro motility assay? AB - With sliding actin-filament motility assays, filament velocity should be independent of changes in the level of actomyosin activation under unloaded conditions. Using a simple modification of the motility assay to measure relative changes in isometric force (activation), we determined that isometric force increased 200-fold with thiophosphorylation of the myosin regulatory light chain, and that with thiophosphorylated myosin, isometric force was further increased by the addition of saturating smooth-muscle tropomyosin (100%) or tropomyosin plus calponin (500%), and decreased with the addition of saturating caldesmon (-100%). Under "reducing conditions," filament velocity (2.0 microns/s) was constant for mixtures of dephosphorylated and thiophosphorylated myosin containing > 5% thiophosphorylated myosin, and was unaffected by the addition of saturating concentrations of tropomyosin or caldesmon. In contrast, "standard assay conditions" were found to be nonreducing. With fully thiophosphorylated smooth muscle myosin, saturating smooth-muscle tropomyosin increased velocity to 150% of control, and caldesmon halted all filament motion; with fully dephosphorylated myosin (< 0.002 mol/mol) filaments only moved when tropomyosin or tropomyosin plus calponin was added. Taken together, these observations suggest that under "standard conditions" a mechanical load is present that is eliminated by "reducing conditions." Filament velocity was insensitive to changes in cross bridge density, under all conditions, suggesting that noncycling cross-bridges, generated by photochemical oxidation of myosin, is a likely source of mechanical loading. PMID- 7787095 TI - Single-molecule mechanics of heavy meromyosin and S1 interacting with rabbit or Drosophila actins using optical tweezers. AB - Single-molecule mechanical interactions between rabbit heavy meromyosin (HMM) or subfragment 1 (S1) and rabbit actin were measured with an optical tweezers piconewton, nanometer transducer. Similar intermittent interactions were observed with HMM and S1. The mean magnitude of the single interaction isotonic displacements was 20 nm for HMM and 15 nm with S1. The mean value of the force of single-molecule interactions was 1.8 pN for HMM and 1.7 pN with S1. The stiffness of myosin S1 was determined by applying a sinusoidal length change to the thin filament and measuring the corresponding force; the mean stiffness was 0.13 pN nm 1. By moving an actin filament over a long distance past an isolated S1 head, we found that cross-bridge attachment occurred preferentially at a periodicity of about 40 nm, similar to that of the actin helical repeat. Rate constants for the probability of detachment of HMM from actin were determined from histograms of the lifetime of the attached state. This gave a value of 8 s-1 or 0.8 x 10(6) M-1 s-1 for binding of ATP to the rigor complex. We conclude (1) that our HMM-actin interactions involve just one head, (2) that compliance of the cross-bridge is not in myosin subfragment 2, although we cannot say to what extent contributions arise from myosin S1 or actin, and (3) that the elemental movement can be caused by a change of shape of the S1 head, but that this would have to be much greater than the movements suggested from structural studies of S1 (Rayment et al., 1993). PMID- 7787098 TI - A single myosin head can be cross-linked to the N termini of two adjacent actin monomers. AB - Myosin subfragment-1 (S1) can be cross-linked to two actin monomers by 1-ethyl-3 [3-(dimethylamino)-propyl]-carbodiimide only when F-actin is in excess over S1. Electron micrographs of the covalent actin2-S1 complex showed that S1 was cross linked to two adjacent monomers of the same actin filament. Cross-linking experiments with pre-proteolyzed S1 derivatives in combination with a proteolytic dissection of the intact covalent actin2-S1 adduct (m = 265 kDa), revealed that two N-terminal segments of actin (residues 1-28) were covalently attached to a single S1 molecule. One was cross-linked to either the 20-kDa or the 50-kDa heavy chain fragments of S1, and the other only to the 50-kDa region. The doubly cross linked product was formed under physiological ionic strength with S1 or with reconstituted myosin filaments, regardless of the presence of ADP or the regulatory proteins, tropomyosin and troponin. Finally, we found that this cross linking could also take place within myofibrils in the rigor state. These results demonstrate that under nonsaturating conditions, the actin-S1 interface encompasses a much larger region than that recently proposed for the nonphysiological, fully saturated actin filaments. PMID- 7787099 TI - Is myosin a "back door" enzyme? AB - ATP has been modeled into the active site of chicken skeletal myosin subfragment 1 using the adenylate kinase.Ap5A structure as a starting reference. The resulting docked ATP.S1 structure is justified in that it rationalizes the photolabeling data from several ATP analogs. The gamma-phosphate of ATP sits at the bottom of the active site pocket and is partially visible via a view along the prominent 50-kDa cleft of S1 but not when viewed from above the active site. It is postulated that actin binding promotes the movement of the P-loop and Arg 245 to allow Pi from ATP to leave via a "back-door" in the 50-kDa fragment while ADP is still bound at the active site. Such a mechanism can explain a number of experimental observations, including the kinetics of ATP hydrolysis, the nucleotide dependence of Pi exchange into ATP, and the formation of stable myosin.ADP.vanadate complexes in muscle fibers. PMID- 7787100 TI - Actin's view of actomyosin interface. AB - Actomyosin interactions were examined by using yeast actin mutants with alanines replacing charged amino acid pairs D24/D25, E99/E100, D80/D81, and E83/K84. In the in vitro motility experiments, actin filaments of D24A/D25A or E99A/E100A mutants moved in the presence of 0.7% methylcellulose at the velocities of wild type actin. Without methylcellulose, these mutant filaments, but not the D80/D81 or E83/K84 filaments, dissociated from the assay surface upon addition of ATP. Measurements of myosin subfragment-1 (S1) binding to D24A/D25A- and E99A/E100A polymerized actins in the presence of ATP revealed a three- and twofold decrease in their binding constant, respectively, compared with wild-type actin. In contrast to this, all monomeric actins had the same binding affinity for S1. The rates and extents of polymerization of D24A/D25A and E99A/E100A actins by S1 were reduced in comparison to wild-type actin. The local structure of subdomain-2 on actin, as probed by subtilisin cleavage, was not altered for either mutant. A twofold decrease in nucleotide exchange was detected for the D24A/D25A mutant actin. These results demonstrate the involvement of the D24/D25 and E99/E100 residues in the weak binding of myosin to actin and reveal that residues D80/D81 and E83/K84 do not modulate actomyosin interactions. PMID- 7787101 TI - The working stroke of myosin crossbridges. AB - Recent x-ray diffraction measurements of the axial periodicities of the actin and myosin filaments in contracting muscles show that they are stretched by small but significant amounts by the developed tension, so that at least one half, possibly more, of the observed compliance of a sarcomere must reside in the filaments themselves. This implies that the movement steps of a crossbridge deduced from quick-release experiments may be shorter than some previous estimates, necessitating at least two steps to account for current in vitro single-molecule measurements. Intensity measurements of the wider angle x-ray reflections also show some unexpected features. PMID- 7787102 TI - Solution structure of two molecular motor domains: nonclaret disjunctional and kinesin. AB - The effects of selected ligands on the structure of the truncated heavy-chain chemomechanical motor domains of Drosophila ncd and human kinesin were compared using the technique of transient electric birefringence. The 366-amino acid C terminal motor domain of Drosophila nonclaret disjunctional, ncd(335-700), and the 349-amino acid N-terminal motor domain of human kinesin, kinesin(349), were studied at 4 degrees C in neutral buffers with ionic strength of 100 mM to form complexes with either MgADP or MgADP.Vi. The rotational diffusion time adjusted to 20 degrees C and water, tau 20,W, for ncd(335-700).MgADP is 32.8 ns, and for ncd(335-700).MgADP.Vi is 34.8 ns, suggesting prolate ellipsoids with dimensions 9.40 x 3.77 nm and 9.73 x 3.70 nm, respectively. The specific Kerr constant, Ksp, of ncd is -1.65 x 10(-12) cm2V-2 for the MgADP complex and -1.15 x 10(-12) cm2V-2 for the MgADP.Vi complex. The large negative Ksp for a prolate protein suggests an unusual charge distribution with two long surfaces with opposite charge. The tau 20,W for kinesin(349).MgADP is longer than the corresponding ncd motor and shows a decrease with increased electric field. The kinesin(349).MgADP.Vi complex has a longer tau 20,W. The Ksp for kinesin(349) is 0.36 x 10(-12) cm2V-2 for each complex. PMID- 7787103 TI - A single-track fluctuation analysis in the sliding movement by protein motors in vitro. PMID- 7787104 TI - Fluctuation analysis of kinesin movement. PMID- 7787105 TI - Is actin-filament velocity in the in vitro motility assay periodic? PMID- 7787106 TI - Force generation in kinesin measured in a centrifuge microscope-based motility assay. PMID- 7787108 TI - Single-molecule kinetic studies on DNA transcription and transcriptional regulation. PMID- 7787107 TI - Motility assays using myosin attached to surfaces through specific binding to monoclonal antibodies. AB - We have analyzed the dependence of actin filament movement on the mode of myosin attachment to surfaces. Monoclonal antibodies that bind to three distinct sites were used to tether myosin to nitrocellulose-coated glass. One antibody reacts with an epitope on the regulatory light chain located at the head-rod junction. The other two react with sites in the rod domain, one in the S2 region near the S2-LMM hinge, and the other at the C terminus of the myosin rod. These monoclonal antibodies were used to provide increasing flexibility in the mode of attachment. Fast skeletal muscle myosin monomers were bound to the surfaces through the specific interaction with these monoclonal antibodies and the sliding movement of fluorescently labeled actin filaments analyzed by video microscopy. Each of these antibodies produced stable, myosin-coated surfaces that supported uniform movement of actin over the course of several hours. Attachment of myosin through the anti-S2 and anti-LMM monoclonal antibodies yielded a maximum velocity of 10 microns/s at 30 degrees C, whereas attachment through anti-LC2 produced a lower velocity of 4-5 microns/s. Each antibody showed a characteristic minimum myosin density below which sliding movement was no longer supported and an exponential dependence of actin filament velocity on myosin surface density below Vmax. Maximum sliding velocity was achieved over a range of myosin surface densities. Thus, the specific mode of attachment can influence the characteristic velocity of actin filament movement and the surface density needed to support movement. These data are being used to analyze the dynamics of sliding filament assays and evaluate estimates of the average number of motor molecules per unit length of actin required to support movement. PMID- 7787109 TI - Single kinesin molecules stressed with optical tweezers. AB - Using the optical tweezers to pull on microtubules, we have stretched and twisted single kinesin molecules adsorbed to glass surfaces. Preliminary measurements suggest that the mechanical system is very compliant, with an apparent stretch of 120 nm with < 2 pN of force. Although measurements of the series compliance of the bead-microtubule structure are still in progress, the kinesin attachment site does not slip with stretch. However, under torsional stress, kinesin appears to slip. With torques < 2 pN-microns approximately 1 Hz in 2 mM AMP-PNP, there is no apparent limit to the number of revolutions that the microtubule can rotate around the kinesin attachment site (n = 44). Preliminary data from other nucleotide conditions are similar. Although there are rare instances of torsional elasticity where the attachment site unwinds, the restoring forces are not constant with angular position, also indicating slippage. Mechanisms of mechanochemical transduction must account for linear force generation in the presence of angular "slippage." PMID- 7787110 TI - Mechanical properties of single protein motor of muscle studied by optical tweezers. PMID- 7787111 TI - Fluorescence polarization from isomers of tetramethylrhodamine at SH-1 in rabbit psoas muscle fibers. AB - We have used fluorescence polarization to examine orientational changes of the 5- and 6-isomers of acetamidotetramethylrhodamine (ATR) covalently bound to SH-1 (Cys-707 of the myosin heavy chain) in single, skinned fibers from rabbit psoas muscle after rapid length steps or photolysis of caged nucleotides. Similar results were obtained with both the 5- and 6-isomers of ATR. After the photolysis of caged ATP, large and rapid changes in the fluorescence polarization signals were observed and were complete well before appreciable force had been generated. Changes in the fluorescence polarization signals after the photolysis of caged ADP were similar to those after the photolysis of caged ATP, despite an almost negligible change in force. The fluorescence polarization signals remained almost constant after rapid length steps in both rigor and active muscle fibers. These results suggest that structural changes at SH-1 monitored by 5- or 6-ATR are not associated directly with the force-generating event of muscle contraction, but may be involved in the communication pathway between the nucleotide and actin binding sites of myosin. PMID- 7787112 TI - Three-dimensional structure of the acrosomal filament of Limulus sperm by 400 kV electron cryomicroscopy. AB - The acrosomal bundle of Limulus sperm was imaged by electron cryomicroscopy, and the three-dimensional structure of a filament computationally isolated from the bundle was determined by helical image reconstruction. The actin model of Holmes was fit into the map, and its interactions with scruin, the actin-binding and cross-linking protein, were studied. Scruin binds to two consecutive actins along the helix via subdomains 1 and 3. These interactions involve helix-loop-beta motifs that are present in both actin subdomains (in different monomers) in positions available for binding by the same scruin molecule as it wraps around the actin. Taking first the structural motif homology and then looking for sequence pattern similarities, a stretch of 12 out of 20 matches in hydrophobicity is found. Scruin itself has been found to have an internal tandem homology. PMID- 7787113 TI - Transients of fluorescence polarization in skeletal muscle fibers labeled with rhodamine on the regulatory light chain. AB - Structural changes of the myosin heads were correlated with mechanical events in the cross-bridge cycle by measuring fluorescence polarization signals at high time resolution from rhodamine probes bound to myosin regulatory light chains in skeletal muscle fibers. Motions of the cross-bridges were partially synchronized either by applying quick length changes to the fibers during active contractions or by activating the fibers from rigor by photolysis of caged ATP in the presence of Ca2+. With fibers in rigor, the fluorescence polarization values indicate that the probe dipoles are quite well ordered and are directed away from the muscle fiber axis. After photorelease of ATP from caged ATP, changes in polarization signals are consistent with broadening of the distribution of probe orientations. The signal deflections occur when ATP binds to actomyosin or when the cross bridges detach, but the orientational distribution changes surprisingly little during active force development. In contrast, when staircases of quick releases are applied to labeled fibers during active contractions, the fluorescence polarization signals suggest a concerted rotation of the probes. The results indicate that the light chain region of myosin tilts during the quick release and/or during the tension recovery phase within the next few ms. PMID- 7787114 TI - Millisecond time resolution electron cryo-microscopy of the M-ATP transient kinetic state of the acto-myosin ATPase. AB - The structure of the AM-ATP transient kinetic state of the acto-myosin ATPase cycle has been examined by electron microscopy using frozen-hydrated specimens prepared in low ionic strength. By spraying grids layered with the acto-S1 complex with ATP immediately before freezing, it was possible to examine the structure of the ternary complex with a time resolution of 10 ms. Disordered binding of the S1 was observed, suggesting more than one attachment geometry. This could be due to the presence of more than one biochemical intermediate, or to a single intermediate binding in more than one conformation. PMID- 7787117 TI - Fetal cells in maternal blood. AB - Fetal cells have been successfully detected in maternal blood in all three trimesters of gestation in a substantial proportion of normal pregnancies. Various enrichment techniques have been developed for fetal trophoblast cells, leucocytes and nucleated red blood cells. Nucleated red blood cells are considered to be best suited for noninvasive prenatal diagnosis. Fluorescence in situ hybridization detected the first cases of fetal trisomy in maternal blood after enrichment of fetal nucleated red blood cells. Despite recent encouraging results, accurate and reproducible diagnoses of fetal anomalies by polymerase chain reaction or fluorescence in-situ hybridization require further optimization of enrichment devices and detection protocols. PMID- 7787118 TI - Chorionic villus sampling. AB - Chorionic villus sampling (CVS) has the great advantage over mid-trimester amniocentesis of producing early results. Moreover, rapid analytic techniques have significantly reduced the waiting time between sampling and diagnosis, whereas progress in recombinant DNA technology and human gene mapping has led to an increase in the range of conditions it can detect. The role of CVS in twin pregnancy has been investigated and compared with amniocentesis. Although these techniques are equally safe, CVS should be considered the approach of choice because of a number of technical advantages, and in relation to selective fetal reduction in discordant twins. Confined placental mosaicism has been investigated and a list of chromosomes related to adverse pregnancy outcome has been compiled. Recent reports have substantially contributed to solving the controversy on the hypothetical relationship between limb reduction defects and CVS. Analysis of limb reduction defects among more than 130,000 cases reported to the World Health Organization CVS registry has been unable to find any relationship between sampling and fetal malformations, including limb reduction defects. PMID- 7787119 TI - Early amniocentesis. AB - Amniocentesis before 15 weeks has been introduced in many prenatal diagnosis centres. There are, however, major anatomical differences between the appearance of fetus at 15-16 weeks, when amniocentesis has normally been performed, and in the first and early second trimester. This is mainly because of the presence of extraembryonic coelome and the relatively small amount of amniotic fluid in early pregnancy. Several small cohort studies have indicated no increased fetal loss rate with early amniocentesis. Others have suggested an increased risk of respiratory distress among the newborn. The only randomized study published, however, found a significantly increased rate of fetal losses after early amniocentesis. This incomplete study indicates the urgency of further randomized studies of early amniocentesis. A randomized study comparing early amniocentesis with transabdominal chorionic villus sampling is being undertaken at our centre in Copenhagen using a filter method that reduces the volume of fluid needed for karyotyping. PMID- 7787115 TI - Changes in the x-ray diffraction pattern from single, intact muscle fibers produced by rapid shortening and stretch. AB - Changes in the x-ray diffraction patterns produced by 100-microseconds-length steps imposed during tetanic stimulation were recorded from single intact fibers of frog tibialis anterior muscle. For shortening steps, a staircase length change was applied, with a 20-ms interval between steps. For stretches, each 20-ms cycle started with a stretch, followed after 4 ms by shortening to the original length. Each shortening step in the staircase and each stretch in the stretch/shortening protocol produced a response similar to that of a single step from the isometric steady state. The intensity of the 14.5-nm x-ray reflection arising from the axial repeat of the myosin heads along their filaments decreased after both shortening and stretch; this decrease was not accompanied by broadening along or across the meridian. The relationship between the intensity after the length step and step amplitude was approximately linear for both stretches and shortening steps, extrapolating to zero intensity for 11-nm stretches and 13-nm shortening steps, but there was no significant intensity change for the first approximately 2 nm of shortening. These results are broadly consistent with conventional models of muscle contraction in which myosin heads move through about 10 nm during the working stroke in the shortening direction, but an additional distortion of the myosin heads may be produced by a stretch. PMID- 7787116 TI - X-ray evidence that in contracting live frog muscles there exist two distinct populations of myosin heads. AB - Using synchrotron radiation and whole muscles, 2 ms time-resolved x-ray diffraction patterns were recorded at 8 degrees C. The results show that in both isotonic and isometric contractions, as well as in length changes imposed at maximum tension [Po], the meridional third myosin layer line consists of two distinct reflections with different intensities and spacings that measure approximately 14,623 and 14,412 nm at Po. Although the intensity behavior of the two reflections is strikingly different during quick releases, it is very similar during stretches. Study of the time courses indicates that myosin heads diffracting at Po with the approximately 14.623 nm periodicity are actively involved in tension production. Those diffracting at Po with the periodicity of approximately 14.412 nm appear not be associated with tension production during isometric contraction and releases, but the results suggest that they are recruited during stretches and here contribute to tension production. Our most important conclusion is that under all conditions of contraction we have investigated there exist two populations of myosin heads, each with a well defined axial disposition and configuration. PMID- 7787121 TI - Multifetal pregnancy reduction and selective termination. AB - Multifetal pregnancy reduction has had a major impact upon perinatal morbidity and mortality following iatrogenic multiple pregnancies. There are still residual risks, however, that are higher for higher order multiples than for pregnancies that started out at lower numbers. There are many, but not complete, parallels between reductions for number per se, and selective termination because of diagnosed abnormalities. PMID- 7787120 TI - Early detection of structural anomalies and markers of chromosomal aberrations by transvaginal ultrasonography. AB - Transvaginal ultrasonography is emerging as the newest method for the early detection of structural malformations and markers of chromosomal aberrations. According to a multicenter registry on the onset of fetal anomalies, many defects are potentially detectable at an early transvaginal scan. Moreover, cystic hygroma and other nuchal signs thought to indicate a very significant risk for a genetic problem detected during the first trimester may resolve and not be detected at the later abdominal scan. Current research presented in this review indicates a possible transition from an abdominal scan at 18-22 weeks to two scans: an early transvaginal scan at 12-14 weeks for the detection of gross congenital anomalies and markers of chromosomal aberrations, and then an abdominal scan at 22 weeks for cardiac and other anomalies. PMID- 7787124 TI - The pathophysiology of premature rupture of the membranes. AB - Premature rupture of the membranes (PROM) is the condition in which the chorioamnion is disrupted before the onset of labor. This condition creates a dilemma for the practicing obstetrician, because once the membranes have broken the risk of fetal or maternal infection, or both, increases. Preterm PROM adds to this management challenge, mainly because of the added problem of prematurity. Although the epidemiology of PROM has been well defined, the exact etiology has yet to be understood. However, using the associated clinical risk factors of PROM, researchers in this field have contributed to our understanding of the causes. Various mechanisms have been proposed, including mechanical, as well as infectious or inflammatory processes. The purpose of this article is to review the various proposed mechanisms of PROM. Maternal risk factors for PROM are presented, mainly to place into context the current literature involving both in vitro and in-vivo research. It is apparent that a single pathophysiologic mechanism is not responsible for all cases of PROM, but rather a combination of processes is in operation. PMID- 7787123 TI - Low-dose aspirin therapy in obstetrics. AB - The results of four large controlled clinical trials, encompassing over 13,000 pregnant women, indicate that low-dose aspirin is of benefit in the prevention of pre-eclampsia in women at high risk. The preventive effect on fetal growth retardation seems to be small, and no therapeutic benefits could be established. Low-dose aspirin appears to be safe for mother, fetus, and neonate. PMID- 7787125 TI - Antepartum fetal surveillance. AB - In recent years the advances in prenatal diagnosis of fetal asphyxia have been dramatic and increasing at a remarkable pace. Now that a solid base of multivariable testing has been accepted as the method of choice for assessment of fetal health, the focus of clinical research has shifted towards identification of factors and signs that might predict not only risk of death and immediate morbid outcome but also the quality of life after delivery. The papers reviewed here outline the scope of the problem of cerebral palsy and offer clues as to how fetal disease may become manifest as child or adult sustained neurological injury. Concurrently, the advances in refinement of the testing methods are reviewed. Clearly a better understanding of the etiology, physiology, and range of fetal responses to asphyxia will be the key to effecting not only better survival rates but also a higher quality of survival. PMID- 7787127 TI - Early prenatal diagnosis: a range of diagnostic tools: selection or combination? PMID- 7787122 TI - Congenital infection. AB - The past year has shed much new light on congenital infection. A key development has been the application of polymerase chain reaction technology to the diagnosis of intrauterine infection. This technique appears to be the diagnostic tool of choice for toxoplasmosis and cytomegalovirus. Pharmacologic treatment appears to reduce the sequellae of toxoplasmosis when treated either in utero or postnatally. Obstetric interventions may reduce vertical transmission. Education has been shown to reduce the incidence of seroconversion for toxoplasmosis, and HIV-positive women treated with zidovudine have a dramatically reduced rate of transmission to their offspring. PMID- 7787126 TI - A large placental venous lake. PMID- 7787128 TI - Nutritional supplementation and prevention of congenital abnormalities. AB - Recent intervention studies have shown a reduction of occurrence and recurrence of neural tube defects caused by the periconceptional supplementation of folic acid-containing multivitamins or pharmacological doses of folic acid alone. This new primary preventive method can also reduce the occurrence of other major congenital abnormalities, mainly the reduction of conotruncal cardiovascular malformations, defects of the urinary tract, congenital hypertrophic pyloric stenosis and congenital limb deficiencies. The rate of cleft lip, palate, or both, was not lowered by periconceptional multivitamin supplementation, however. The underlying biologic mechanisms of this protective effect are not still understood, but naturally occurring folates (polyglutamates) or synthetic folic acid (monoglutamate) have a key role. The debate over supplementation concerns which vitamins (folic-acid-containing multivitamins, or folic acid alone); what doses (0.4 mg, 0.8 mg or 4 mg folic acid) and to whom (whether it is worthwhile differentiating between women at high and low risk). At present there are three possibilities: folate- and other vitamin-rich diet, supplementation, and food fortification to provide appropriate multivitamin and folic acid consumption for all women of childbearing age who are capable of becoming pregnant. PMID- 7787129 TI - Pharmacokinetics of amoxicillin coadministered with a saline-polyethylene glycol solution in healthy volunteers. AB - The pharmacokinetics of orally administered amoxicillin were investigated in 12 healthy volunteers in a crossover design. They received either a placebo or a saline-polyethylene glycol solution (SPG) for 4 d, the last dose being given simultaneously with 1 g amoxicillin; blood samples were drawn for the next 12 h. Amoxicillin kinetics were similar in the two treatments but small differences in some pharmacokinetic parameters reached significance. The mean +/- SD area under the curve was lower with SPG (43.8 +/- 6.8 against 47.8 +/- 8.2 mg h L-1, p < 0.05) but the treatments were equivalent according to Westlake's test (95% confidence interval = 14.95%). Analysis of SPG against placebo amoxicillin absorption kinetics after fitting the data to a Weibull model revealed a longer duration of the absorption, a slower rate of absorption, and a different shape of the curve. No clinical consequences are expected from these minor variations but possible mechanisms could be relevant to other drugs. PMID- 7787130 TI - Pharmacokinetics of dolasetron following single- and multiple-dose intravenous administration to normal male subjects. AB - Dolasetron, Anzemet, a 5-hydroxytryptamine receptor antagonist, is under investigation as an antiemetic agent. The keto-reduced metabolite of dolasetron has been identified in human plasma and is probably responsible for the majority of the antiemetic activity. This study evaluated the pharmacokinetics of dolasetron and the reduced metabolite following single and multiple intravenous (IV) infusions of dolasetron mesylate in healthy male subjects. Four groups of subjects (six active/two placebo) received either dolasetron mesylate or placebo in single IV doses ranging from 0.30 to 0.60 mg kg-1 on day 1 and multiple IV doses ranging from 0.60 to 1.20 mg kg-1 d-1 on days 2-9. Dolasetron could be detected for less than 1 h, while the reduced metabolite appeared rapidly in the plasma, reaching a maximal plasma concentration in less than 1 h. Reduced metabolic maximal plasma concentration was proportional to the dose and the area under plasma concentration curve was linear based on regression analysis. The half-life of reduced metabolite ranged from 3.82 to 7.46 h. The mean renal clearance of reduced metabolite was 2.20-4.43 mL min-1 kg-1 and was dose independent. All of the evidence supports dose independent pharmacokinetics for the reduced metabolite. Upon multiple dosing, the reduced metabolite AUC can be predicted from the single-dose pharmacokinetics of this metabolite. PMID- 7787132 TI - Pharmacokinetic analysis of diethylcarbonate prodrugs of ibuprofen and naproxen. AB - The pharmacokinetics of ibuprofen diethylcarbonate (ibudice) and naproxen diethythylcarbonate (napdice), two new diethylcarbonate prodrugs of ibuprofen and naproxen, was investigated in dogs. The rationale for the development of ibudice and napdice was that esterification of the carboxylic moiety of the parent compounds would suppress gastrotoxicity without adversely affecting their anti inflammatory activity. In addition the biotransformation of the prodrugs to the parent compounds may be utilized to achieve rate and time controlled drug delivery of the active entities. Following oral administration the diethylcarbonate esters were rapidly biotransformed to the parent compounds and no ibudice or napdice was detected in the plasma. The relative bioavailability of ibuprofen and naproxen, following oral administration of ibudice and napdice, was 96% and 74%, respectively, and the rate of absorption was not significantly different from that obtained following oral dosing of the parent compound. Stability studies in gastric and intestinal juice showed that, unlike napdice, ibudice was stable in gastric juice, with both prodrugs undergoing rapid biotransformation to their parent compounds in intestinal juice. This rapid conversion led to the lack of sustained release performance following oral administration of ibudice or napidice. PMID- 7787131 TI - The effect of food on the absorption of 14C-SDZ FOX 988, an antidiabetic agent, in healthy human volunteers. AB - The objective of this study is to examine the effect of food on oral absorption of SDZ FOX 988 (FOX 988), an antidiabetic agent, and circulating levels of its active metabolite, SDZ 53-450 (53-450). Sixteen normal volunteers received a single 10 mg dose of 14C-FOX 988, either as gelatin capsules or in a suspension (0.5% CMC). For subjects receiving each formulation, four subjects received a meal, consisting of 50% fat by calories, immediately following dosing, while the other four received the same meal at 2 h post-dose. Serial blood, urine, and fecal samples were collected for 120 h and analyzed for total radioactivity. Blood concentrations of 53-450 were analyzed using an HPLC-UV method. Concomitant administration with food increased the extent of FOX 988 absorption from either suspension or capsule, as shown by an increase in AUC and in urinary recovery of radioactivity. Blood concentrations of 53-450 were only detected in subjects receiving food at dosing. No difference in absorption was observed between the capsule and the suspension. Results from this study showed that oral absorption of FOX 988 is enhanced by co-administration of food in normal volunteers. PMID- 7787133 TI - Disposition of [3H]fluvastatin following single oral doses in beagle dogs and rhesus monkeys with bile fistulae. AB - The disposition of [3H]fluvastatin was examined following single oral doses in dogs (12.4 mg kg-1) and monkeys (0.48 and 45.5 mg kg-1) with bile fistulae. Serial plasma and complete urine, feces, and bile were collected at designated intervals for 3 or 4 d, and were analyzed for total radioactivity and unchanged fluvastatin. In the dog, peak radioactivity concentrations (Cmax) averaged 7260 ng equiv. mL-1 and the mean time to peak (tmax) was approximately 9 h. In the monkey, the mean radioactivity tmax values were approximately 5 and 13 h following the low and high doses, the respective Cmax values being 116 and 10,400 ng equiv. mL-1. The mean AUC of total radioactivity was proportional to the dose while that of fluvastatin was overproportional to dose, suggesting dose independent absorption but saturable first-pass effect. The AUC ratio of unchanged fluvastatin versus total radioactivity was approximately 63% in the dog, and 9% and 13% for the low and high doses, respectively in the monkey. The bile was the major excretory route of radioactivity (dog, 56%; low-dose monkey, 73%; high-dose monkey, 69%) whereas the renal pathway accounted for < 5% of the dose in both species. Approximately 12% of the biliary radioactivity in the dog was due to intact fluvastatin, compared with 0% and 7.5% after the low and high doses in the monkey. These results showed a smaller extent of fluvastatin metabolism in the dog than in the monkey, and suggested that metabolism in the monkey was saturable in the dose range studied. PMID- 7787134 TI - The influence of food intake on the effect of two controlled release formulations of furosemide. AB - Differences in the urinary excretion rate of furosemide may explain discrepancies observed between the bioavailability and the total diuretic effect of different formulations of this drug. Furosemide was given at a dose of 60 mg as two oral controlled release (CR) formulations (FR and LR), with and without breakfast, in a randomized, four-treatment, four-period, crossover design to 28 healthy volunteers. Urinary volume, and contents of furosemide and sodium, were measured in samples taken over 24 h. The extent and rate of absorption of furosemide from FR were decreased after breakfast as compared to fasting: the mean (SD) of total furosemide excreted decreased from 11.38 (3.12) to 7.73 (1.67) mg, p < 0.0001, and the median (range) mean residence time increased from 6.3 (4.1-9.3) to 9.5 (5.9-11.8) h, p < 0.001. On the other hand, the extent of absorption of LR was increased after breakfast, from 8.04 (3.32) to 9.45 (1.83) mg, p < 0.05, without a significant change in MRT. FR had a higher extent and rate of absorption than LR during fasting, but its extent of absorption was lower than that of LR in the postprandial state. Interestingly, the total fraction of furosemide absorbed, as estimated from total furosemide excretion, was not correlated with the total diuresis (r2 = 0.079) and the differences in drug response compared among the four periods were much smaller than would be expected from the differences in amount absorbed. This discrepancy may be explained by differences in urinary excretion rate of furosemide and, related to this, differences in efficiency profiles between the four treatments. Therefore, the urinary excretion profile of a formulation of furosemide may be more important for the cumulated drug effect than the amount absorbed. PMID- 7787135 TI - The influence of pyruvic acid on the pharmacokinetics of sulphadiazine in rabbits. AB - During the past few years, acetylation polymorphism has been shown to be a proven, established fact, and N-acetyltransferase, an enzyme that transfers an acetyl group to the substrate, has been recognized as the main factor in acetylation polymorphism. In a recent study, a significant difference between the acetylation phenotype and plasma pyruvic acid (PA) concentration in rabbits was found. In this report, the influence of PA on the pharmacokinetics of sulphadiazine (SDZ), a drug that has been used in pharmacogenetic studies of acetylation, was studied. By using a loading dose of 300 mg kg-1, and an infusion rate of 7.5 mg min-1 kg-1 of PA, the concentration of PA reached a steady state (Css approximately equal to 100 micrograms mL-1) in 30 min. During PA infusion in rapid-acetylation rabbits, no significant changes were found in any of the pharmacokinetic parameters for SDZ. However, differences were found in the beta half-life, AUC, clearance, and k10 of SDZ in slow acetylators: the beta half-life decreased from 115.74 +/- 12.47 min to 62.96 +/- 4.36 min (p < 0.001); AUC decreased from 10,617.38 +/- 1179.81 micrograms min mL-1 to 6217.14 +/- 391.32 micrograms min mL-1 (p < 0.001); clearance increased from 0.0044 +/- 0.0008 L min 1 kg-1 to 0.0068 +/- 0.0007 L min-1 kg-1 (p < 0.001); and k10 increased from 0.0090 +/- 0.0009 min-1 to 0.0193 +/- 0.0028 min-1 (p < 0.005). The reason for this may be that PA influences the elimination of SDZ in slow-acetylation rabbits. PMID- 7787136 TI - The effect of water deprivation on the pharmacokinetics of methotrexate in rats. PMID- 7787137 TI - The effect of dehydration on the disposition kinetics of propranolol in rats. PMID- 7787138 TI - Presidential address. Personal views on health care issues. PMID- 7787139 TI - Structure-stabilizing forces in the glomerular tuft. AB - The glomerular tuft is constantly exposed to considerable expansile forces resulting from high capillary pressures. Counterforces must be generated in order to maintain structural stability. This review analyzes those structures of the glomerular tuft capable of developing such stabilizing forces. Two systems are described. A basic system consists of the glomerular basement membrane (GBM) and the mesangium. The GBM represents the main skeletal element of the glomerular tuft. In general, opposing portions of the GBM are bridged by contractile mesangial cell processes, generating inwardly directed forces that balance the expansile forces resulting from pressure gradients across the GBM. A second structure-stabilizing role of the podocytes appears to be superimposed on this system. Podocytes are attached to the GBM by numerous foot processes that contain a contractile system. The foot process attachments probably stabilize small patches of the underlying GBM, counteracting local elastic distension. In addition, podocytes may contribute to the stabilization of the folding pattern of the tuft by linking neighboring capillary loops to each other. PMID- 7787141 TI - Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease. AB - Intravenous immune globulin (IVIg) has been advocated as efficacious therapy for a variety of disorders including idiopathic thrombocytopenic purpura and Kawasaki disease. Several reports have also documented the effectiveness of IVIg in systemic lupus erythematosus (SLE). Two patients with symptomatic SLE and ESRD were treated with IVIg. Both patients tolerated IVIg administration well and demonstrated clinical and serologic improvement. Both individuals also experienced a transient decline in serum albumin concentration with IVIg treatment. The mechanisms by which IVIg might have effected improvement in these patients are varied and are likely related to the immunomodulatory actions of IVIg. The reversible change in albumin concentration seen in these individuals may be secondary to abrupt alterations in oncotic homeostasis. Despite this unusual effect, the documented improvement in these patients suggests that IVIg therapy may be of benefit in patients with active SLE and ESRD. Further studies are warranted to examine the mechanisms by which IVIg may exert its therapeutic effect. PMID- 7787140 TI - Rapidly progressive glomerulonephritis after immunotherapy for cancer. AB - Cytokines have been used in experimental and standard protocols for immune enhancement for cancer. The combination of interleukin-2 and interferon-alpha 2 beta has been used in experimental protocols for metastatic renal cell carcinoma. A man who developed rapidly progressive renal failure after receiving this combination therapy is reported. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were absent. The spectrum of renal disease and potentially related extrarenal manifestations associated with interleukin-2 and inteferon-alpha are reviewed. A pathogenesis of altered cell mediated immunity, consistent with abnormalities in extrarenal organs after immune enhancement, is proposed. PMID- 7787142 TI - Renal hemodynamics and sodium handling in moderate renal insufficiency: the role of insulin resistance and dyslipidemia. AB - Insulin infusion during euglycemia causes antinatriuresis and renal vasodilation in healthy humans, whereas the effects of acute insulin infusion on tubular sodium handling and renal hemodynamics in chronic renal disease are unknown. The response to euglycemic insulin infusion was investigated in two homogeneous patient groups with a slight renal impairment-one with nephrotic syndrome (GFR, 64 mL/min; N = 9) and one with non-nephrotic immunoglobulin A nephropathy (GFR, 70 mL/min; N = 8). In addition, nine renal transplant recipients (GFR, 44 +/- 6 mL/min) were investigated. The results were compared with those of 12 healthy controls (GFR, 105 +/- 4 mL/min). Renal hemodynamics and renal tubular sodium handling were estimated with inulin, p-aminohippurate, sodium, and lithium clearances. The results showed that patients with nephrotic syndrome (5.0 +/- 0.4 mg/kg per minute) and renal transplant recipients (4.8 +/- 0.6 mg/kg per minute) had a significant lower metabolic clearance of glucose as compared with control subjects (7.9 +/- 0.4 mg/kg per minute), whereas patients with immunoglobulin A nephropathy (6.7 +/- 0.6 mg/kg per minute) had a metabolic clearance of glucose that was similar to that of the controls. Despite insulin resistance to carbohydrate metabolism, insulin infusion still induced hypokalemia and antinatriuresis in patients with nephrotic syndrome and renal transplant recipients. Insulin infusion caused a significant 13% increase in RPF and lithium clearance in control subjects, and a positive Spearman rank correlation (Rs = 0.41; P < 0.05) was observed between the changes in p-aminohippurate and lithium clearances during insulin infusion in the combined patient group, suggesting that impaired renal vasodilation may contribute to abnormal proximal tubular sodium handling and sodium retention. The results also suggest that hypertriglyceridemia could be a factor contributing to abnormal proximal tubular sodium handling in chronic renal disease. PMID- 7787144 TI - Impaired renal autoregulatory ability in dogs with reduced renal mass. AB - In normal dogs, the renal autoregulatory mechanism limits the effect of changes in renal arterial pressure (RAP) on RBF, renal outer cortical blood flow (OCBF), and GFR by adjusting the vascular tone of the preglomerular arterioles. To determine the extent to which autoregulatory ability was impaired in remnant renal tissue in dogs, the effects of variations in RAP on RBF, OCBF, and GFR were studied after sham-operation (Group 1; N = 5), 3/4 nephrectomy (Group 2; N = 5), or 7/8 nephrectomy (Group 3; N = 5). In Group 1, the RBF, OCBF, and GFR were not significantly affected by variations in RAP between 75 and 125 mm Hg, indicating intact renal autoregulatory ability. In contrast, both groups of partially nephrectomized dogs exhibited a loss of renal autoregulatory ability below 100 mm Hg (P < 0.05). As RAP rose above 100 mm Hg, dogs with 7/8 nephrectomy exhibited a greater increase than control dogs in RBF (0.586 +/- 0.211 versus -0.080 +/- 0.030 percent change in RBF/mm Hg change in RAP; P < 0.05), OCBF (0.408 +/- 0.157 versus -0.059 +/- 0.054 percent change in RBF/mm Hg change in RAP; P < 0.05), and GFR (0.784 +/- 0.230 versus 0.134 +/- 0.049 percent change in RBF/mm Hg change in RAP; P < 0.05). The ability of the renal vasculature to maintain renal function stable above 100 mm Hg was intermediate in Group 2 and not significantly different from corresponding values for Group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787143 TI - Renal hemodynamics and plasma and kidney angiotensin II in established diabetes mellitus in rats: effect of sodium and salt restriction. AB - Six weeks after the onset of insulin-treated streptozotocin diabetes (STZ) in Munich-Wistar rats, the effect of a low-sodium (LNa) and a low-salt (LNaCl) diet on renal function and on plasma and kidney tissue angiotensin II (AIIp, AIIk) was tested. Clearance experiments were performed in anesthetized rats 7 days after starting on LNa or LNaCl. On a control diet, STZ exhibited an increase in GFR, RBF, and kidney weight (KW) and a reduction in renal vascular resistance (RVR) and AIIk, but no change in AIIp, compared with nondiabetic normal rats (CON). Although sodium restriction reduced and salt restriction increased AIIk in CON, both diets increased AIIp without affecting renal hemodynamics or KW. In diabetic rats, both salt and sodium restriction further increased GFR and RBF by reducing RVR, increased KW, and changed AIIk and AIIp in a similar pattern, but at significantly lower values compared with CON. Daily treatment of STZ-LNa with the AII-receptor blocker losartan (20 mg/L, in drinking water) did not affect the reduction in RVR and the increase in KW but slightly reduced RBF because of a decrease in mean arterial blood pressure and further increased GFR. It was concluded that (1) AIIk but not AIIp is affected differently by LNa compared with LNaCl in both CON and STZ; (2) LNaCl and LNa change AIIp and AIIk in a similar pattern but at significant lower values in STZ compared with CON; and (3) with regard to renal hemodynamics and KW, the response to LNa and LNaCl is different in CON compared with rats 6 wk after the onset of diabetes mellitus, the latter exhibiting a further increase in renal hyperfiltration and KW by a mechanism that is not directly AII receptor dependent. PMID- 7787145 TI - The study of the effect of intensity of blood pressure management on the progression of type 1 diabetic nephropathy: study design and baseline patient characteristics. Collaborative Study Group. AB - A randomized, prospective, clinical trial has been initiated to continue follow up in a subset of the patients previously enrolled in the recently completed Study of Angiotensin-Converting Enzyme Inhibition (ACEi) in Type 1 Diabetic Nephropathy. In that study, the use of captopril was associated with a 48% reduction in the risk of doubling the serum creatinine and a 50% reduction in the risk of experiencing dialysis, transplantation, or death, compared with the use of placebo. These effects were independent of captopril's effect on the blood pressure. This study is designed to determine whether the level of mean arterial blood pressure (MAP), using the ACE inhibitor ramipril as the primary therapy, is associated with an improved prognosis of diabetic nephropathy with respect to (1) the rate of decline in renal function; (2) the rate of progression to end-stage renal failure; (3) the clinical course of proteinuria; (4) morbidity; and (5) mortality. Patients are randomized into one of two distinct blood pressure control groups, an Intensive Group #1, MAP < or = 92 mm Hg; and a Moderate Group #2, MAP 100 to 107 mm Hg. Patients previously enrolled in the "Study of ACEi in Type 1 Diabetic Nephropathy" whose serum creatinine was less than 4.0 mg/dL (354 mumol/L) were eligible for randomization into this study. All patients will receive ramipril (2.5 to 10.0 mg/day) as the primary therapy, with the addition or removal of other antihypertensive agents as needed to achieve the assigned blood pressure goal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787146 TI - Prostaglandin F2 alpha- and 12-O-tetradecanoylphorbol-13-acetate-induced alterations in the pathways of renal ammoniagenesis. AB - The mechanisms whereby prostaglandin F2 alpha (PGF2 alpha) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit ammoniagenesis and the reason why they behave differently at pH 7.4, were examined with (15N)glutamine to assess the metabolic pathways and 2'-7'-bis(2-carboxyethyl)-5-(and-6) carboxylfluorescein, acetoxymethylester (BCECF-AM) to evaluate Na+/H+ antiporter activity. LLC-PK1 cultures were incubated for 1 h in a Krebs-Hensleit bicarbonate buffer of pH 7.4 and pH 6.8 supplemented either with 5-15N- or 2-15N-labeled glutamine, followed by the assessment of (15N)ammonia and (15N)amino acid formation. Exposure of cells to either PGF2 alpha or TPA completely inhibited the low pH-induced increases in (15N)ammonia formation from incubations with 5-15N, reflecting reduced flux through the mitochondrial phosphate-dependent glutaminase, and from (2-15N)glutamine, reflecting reduced flux through the mitochondrial glutamate dehydrogenase pathway. They also qualitatively reversed the acute acidosis-induced changes in (15N)alanine formation and (15N)glutamate accumulation in the media. By contrast only TPA, but not PGF2 alpha, modified glutamine metabolism at pH 7.4. Na+/H+ antiporter activity was assessed under both acidified and basal (pH 7.4) conditions by measuring changes in intracellular pH in cells loaded with BCECF. TPA and PGF2 alpha both stimulated Na+/H+ antiporter activity comparably under acidified conditions. When cells were studied at pH 7.4, TPA but not PGF2 alpha stimulated the Na+/H+ antiporter and increased steady-state intracellular pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787147 TI - Modifications in glomerular polyanion distribution in adriamycin nephrosis. AB - Previous reports have suggested that, in proteinuria induced by adriamycin (ADR), the functional size barrier of the glomerular basement membrane (GBM) is altered as the result of a sieving defect, whereas the functional charge barrier of the glomeruli remains intact. The aim of this study was to reevaluate the effect of ADR on anionic constituents in the glomerular capillary wall (GCW). Kidneys of nephrotic rats, induced by the injection of 7.5 mg/kg ADR, and controls were resected, and cortices were isolated 24 h and 10 days postinjection, fixed with formaldehyde, and embedded in paraffin. For the histochemical evaluation of sialyl residues, deparafinized sections were treated with biotin-labeled peanut agglutinin (PNA), before or after neuraminidase treatment. PNA binding was visualized by the avidin-biotin-peroxidase complex and interacted with hydrogen peroxide and diaminobenzidine. For electron microscopy, kidney cortices were fixed with glutaraldehyde and embedded in araldite or LR-white. The postembedding localization of anionic sites was carried out by cationic colloidal gold (CCG), directly applied on thin LR-white sections. Although in the 24-h ADR group, kidney functions and glomerular morphology were generally unaltered, the 10-day ADR group exhibited severe proteinuria, hypoalbuminemia, and massive fusion of intercalated foot processes of the podocytes. Intense PNA binding was observed after neuraminidase treatment in the GCW of the controls. This was gradually decreased in the 24-h ADR kidneys and further decreased in the 10-day ADR, indicating a gradual decrease in glomerular sialic acid content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787148 TI - Familial risk, age at onset, and cause of end-stage renal disease in white Americans. AB - A strong familial clustering of ESRD has been reported among African Americans, suggesting that factors predisposing to renal failure, whether genetic, environmental, or both, may disproportionately affect certain families. A case control study was undertaken to determine if a familial risk of ESRD was present among white Americans, if this risk differed among causes of ESRD, and if variability in age at onset was attributed to familial factors. Data were obtained from 103 white American patients (cases) with ESRD receiving dialysis treatments at the Bowman Gray School of Medicine's affiliated dialysis facility in Winston-Salem, NC. One hundred three age-, sex- and race-matched non-ESRD controls were consecutively selected from the Wake Forest University Physicians internal medicine clinic. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated to signify the prevalence of a relative with ESRD among cases versus controls. The presence of either a first- or second-degree relative increased a white American's risk for developing ESRD nearly threefold (OR = 2.7, 95% CI 1.1 to 7.2; P = 0.038), whereas the presence of either a first , second- or third-degree relative with ESRD increased the risk nearly fourfold (OR = 3.5, 95% CI 1.5 to 8.4; P = 0.004). Cases with chronic glomerulonephritis and Type II diabetic nephropathy as the cause of ESRD had relatives with ESRD more often than cases with Type I diabetic nephropathy, interstitial nephritis, or renal artery stenosis. The average correlation (f) of ages at onset of ESRD among individuals in a single family (cases and their relatives) was 55%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787149 TI - Dietary vitamin E supplementation ameliorates renal injury in chronic puromycin aminonucleoside nephropathy. AB - Chronic puromycin aminonucleoside nephropathy (PAN) is an experimental analog of focal segmental glomerulosclerosis. Progressive renal damage in this model is partly mediated by excessive production of oxidant species. Whether dietary supplementation with vitamin E, an endogenous lipophilic antioxidant, ameliorates the severity of chronic PAN was tested. PAN was induced by seven serial injections of the glomerular epithelial cell toxin puromycin aminonucleoside, 2 mg/100 g body wt per dose, over a 12-wk period. Experimental animals (N = 8) received vitamin E-enriched chow (100 IU/kg), whereas control PAN rats (N = 10) were fed standard rodent diet containing vitamin E (30 IU/kg of chow). The administration of vitamin E had no effect on somatic growth or blood pressure; however, rats with PAN fed the vitamin E-enriched diet had an increased hematocrit. In addition, the experimental diet resulted in a 50% reduction in urinary total protein and albumin excretion and stabilization of the serum albumin, cholesterol, and triglyceride concentrations (P < 0.01). The inulin clearance was 69% higher in the vitamin E-supplemented animals (P < 0.001). Tubular function, namely, phosphate reabsorption and beta 2-microglobulin excretion, was improved in rats with chronic PAN treated with the vitamin E enriched diet. There was a significant decrease in glomerulosclerosis and glomerular planar area, and tubulointerstitial scarring was diminished in vitamin E-treated animals with chronic PAN (P < 0.01). These beneficial effects on renal structure and function were associated with reduced malondialdehyde content in the kidney and liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787150 TI - Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis. AB - Short-term cyclosporine (CsA) has been shown to reduce the proteinuria in refractory nephrotic syndrome, but the effect on disease progression has not been evaluated. This study was undertaken to evaluate whether maintenance CsA therapy in steroid-resistant focal segmental glomerulosclerosis (FSGS) will prevent progression to ESRD. Twenty-one black and Hispanic children (mean age, 8.4 +/- 4.5 yr) with biopsy-proven, steroid/cyclophosphamide-resistant FSGS were treated with CsA (initiated at 6 mg/kg per day and titrated to the serum cholesterol level to achieve a response). The mean CsA dose was 7 (4 to 20) mg/kg per day, the duration of CsA therapy was 27.5 (3 to 97) months, and the duration of follow up was 8.5 +/- 4.7 yr. At the end of CsA therapy, the mean (+/- SE) proteinuria fell from 6.2 +/- 0.2 to 2.0 +/- 0.1 g/24 h (P < 0.001), the mean albumin rose from 1.95 +/- 0.04 to 3.41 +/- 0.04 g/dL (P < 0.001), the mean cholesterol decreased from 472 +/- 12.7 to 257 +/- 5.3 mg/dL (P < 0.005), and the mean creatinine rose from 0.79 +/- 0.02 to 1.16 +/- 0.03 mg/dL (P < 0.005). Seven children continue to receive maintenance CsA therapy, and 14 patients have had CsA stopped: 6 for an increase in serum creatinine and/or continued proteinuria, 5 for sustained remission, 2 for noncompliance, and 1 for pregnancy. Five (24%) of the 21 patients progressed to ESRD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787152 TI - Comparison of continuous ambulatory peritoneal dialysis-related infections with different "Y-tubing" exchange systems. AB - Despite several modifications of the continuous ambulatory peritoneal dialysis (CAPD) technique over the last decade, peritonitis remains a major source of morbidity and is the leading cause of dropout for patients maintained on CAPD therapy. Recently, Baxter Healthcare introduced the Ultra Twin bag system, which uses drainage and infusion bags both secured to Y connecting tubing. Previous nonrandomized studies comparing the Ultra Twin bag system with other systems have indicated an improvement in the peritonitis rate with the Ultra Twin bag system. In this study, 82 patients were randomized to use the Ultra Twin bag system or the Ultra Y-set system, which uses only the drainage bag already attached to the Y connecting tubing. Peritonitis rates were significantly lower with the Ultra Twin bag system, one episode per 33.9 patient months, compared with the Ultra Y set system, one episode per 11.7 patient months (P < 0.05). Furthermore, the 1-yr infection-free survival rates with the Ultra Twin bag system and the Ultra Y-set system were 71 and 40%, respectively. Exit-site infections were lower with the Ultra Twin bag system, one episode per 12.5 patient months, compared with the Ultra Y-set system, one episode per 28.3 patient months, although this difference was not statistically significant (P = 0.084). The effect of the reduction in the infection rate on patient dropout with the Ultra Twin bag system remains to be addressed. PMID- 7787153 TI - The development of hypertension in the remnant kidney model after either pole resection or partial infarction of the kidney. PMID- 7787154 TI - Ras oncogene and p53 gene hotspot mutations in colorectal cancers. AB - Ras oncogene and p53 gene mutations are frequently observed in colorectal cancers. The role of co-operation between these two genes in the tumorigenesis of colorectal cancer was evaluated. Point mutations in K-ras oncogene and hotspot codons of p53 gene of colorectal cancers were evaluated by naturally created or amplified created restriction site method. Nine of 42 cases (21.4%) of colorectal cancer showed K-ras oncogene mutations. Six of 42 cases (14.3%) of colorectal cancer showed p53 gene hotspot point mutations. The low frequency of p53 gene mutation in this series may be due to racial difference or different hotspot codons. When six cases with mutated p53 gene were examined, only one (16.7%) showed concurrent K-ras oncogene codon 12 and p53 gene codon 248 mutations. We concluded that the co-operation between ras oncogene and p53 gene hotspot point mutations in the tumorigenesis of colorectal cancer in Chinese was not common. Other factors such as adenomatous polyposis coli gene mutations, oncogene activation or tumour suppression gene inactivation may be involved. PMID- 7787155 TI - The effects of abdominal irradiation for seminoma of the testis on gastrointestinal function. AB - To evaluate the long-term effects of abdominal irradiation for the treatment of seminoma of the testis on gastrointestinal function, 15 randomly selected patients who had been treated for stage I seminoma of the testis 2-10 years previously had the following parameters of gastrointestinal function evaluated: gastrointestinal symptoms; absorption of bile acid; vitamin B12; lactose and fat; gastric emptying; small intestinal and total gut transit; and intestinal permeability. Results were compared to those obtained in 18 normal volunteers. There was an increased prevalence of gastrointestinal symptoms (P < 0.01) in the patients and stool frequency was above the control range in two of them. Gastric emptying was faster (P < 0.01) in the patients. There were no significant differences in vitamin B12, bile acid, lactose or fat absorption, small intestinal transit or whole gut transit between the two groups, although faecal fat excretion was greater than the control range in three of the patients. At least one parameter of gastrointestinal function was abnormal in 11 of the 15 patients. Patients with right-sided seminoma had a greater bowel frequency when compared to those with left-sided seminoma (P < 0.05). We conclude that mild abnormalities in gastrointestinal function occur frequently when abdominal irradiation is used to treat stage I seminoma. PMID- 7787151 TI - Behavioral compliance with dialysis prescription in hemodialysis patients. AB - The relationship between compliance and outcome is poorly understood, partially because there has been no gold standard for measuring compliance in hemodialysis patients. To investigate interrelationships between psychological, medical, and compliance factors, hemodialysis (HD) patients were studied with the Beck Depression Inventory, and a subset, the Cognitive Depression Index, the Perception of Illness Effects scale, and the Multidimensional Scale of Perceived Social Support. Behavioral compliance was measured in three ways: (1) percent time compliance (signifying "shortening behavior"); (2) percent attendance (signifying "skipping behavior) (3) percent total time compliance, assessing patients' time on dialysis normalized for prescribed time, including all shortenings and absences. Standard compliance indicators (predialysis serum potassium and phosphorus concentrations and interdialytic weight gain) were also analyzed. The patients' mean Beck Depression Inventory was in the range of mild depression. The prevalence of depression was 25.5%. Both depression indices correlated with Perception of Illness Effects scale scores. In general, social support was related to both measures of depression and perception of illness effects. Total time compliance was 95.8 +/- 5.0%. Younger patients were more likely to skip treatments compared with older patients. Time compliance comprised a wide spectrum, with most patients relatively compliant, whereas a small proportion received far less than their prescribed dialysis. Skipping and shortening behaviors did not correlate, suggesting that these constitute two separate types of noncompliant behaviors. Time compliance parameters did not correlate with potassium levels or interdialytic weight gain, but did correlate with phosphorus levels. Interrelationships between behavioral compliance measures and other parameters varied between units and patients of different gender. Finally, behavioral compliance patterns were stable over months in patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787156 TI - Familial juvenile polyposis with adenomatous-carcinomatous change. AB - A family tree of 118 members with five members found to have juvenile polyposis adenomatous change and four juvenile polyposis-adenomatous-carcinomatous change is presented. All the patients developed bleeding per rectum between 10 and 17 years of age. Four members died of colonic malignancy between 30 and 55 years of age. Colonoscopy in five living members revealed typical juvenile polyps throughout the whole length of the colon and atypical large lobulated polyps containing adenomatous change in juvenile polyps in the rectosigmoid area. An autosomal dominant mode of transmission was evident on analysis of the pedigree. Gastric hyperplastic polyps were present in three of the five living members. Familial juvenile polyposis may have the potential to progress into adenoma carcinoma sequence and is not always a benign disorder. Colonoscopic surveillance should be done to detect adenomatous change if any member of the juvenile polyposis family develops colonic malignancy. PMID- 7787157 TI - A single standard nocturnal dose of nizatidine enhances the healing of active duodenal ulcers among Chinese. AB - Chinese people have a lower maximal acid output and gastrin response to meals compared to Western people. The aim of the present study was to assess the efficacy of a half-single nocturnal dose of nizatidine (150 mg at bedtime [h.s.], n = 40) with a standard full dose given once nightly (300 mg h.s., n = 38) or twice daily (150 mg twice a day [b.i.d.], n = 43) in the treatment of Chinese patients with active duodenal ulcers. An endoscopy was performed upon entry and at 4 week intervals until the ulcer healed (up to 8 weeks). There is no statistical difference in healing rates after 4 weeks of treatment (52.5, 52 and 47% in nizatidine 150 mg h.s., 150 mg b.i.d. and nizatidine 300 mg h.s., respectively) whereas nizatidine 300 h.s. had a significantly higher healing rate compared to nizatidine 150 mg h.s. and b.i.d. after 8 weeks of treatment (89 vs 70 and 67%, P < 0.05) by uni- and multivariate analysis of clinical and endoscopic characteristics. Symptomatic response was not significantly different in these three treated groups. Our study suggested that a half-single nocturnal dose of nizatidine is not ideal for the treatment of duodenal ulcer in Chinese patients, whereas a single standard nocturnal dose appears more effective than a twice-daily regimen. PMID- 7787159 TI - Sulphated macromolecules produced by in vivo labelling in the rat gastric mucosa. AB - The aim of this study was to investigate the nature and distribution of sulphated macromolecules of the extracellular matrix in rat gastric mucosa. This was achieved by developing an in vivo labelling system. An intraperitoneal injection of 1 mCi [35S]-sulphate was given for either 4 h (0.01% incorporation into macromolecular fraction) or 8 h (0.13% incorporation). At the end of the labelling period the stomach was removed and the mucosa and submucosa was either taken as a single combined sample or separated into four layers by blunt dissection. Each sample was papain digested and analysed by ion-exchange chromatography. This analysis revealed sulphated species of differing charge existing in differing proportions throughout the mucosa. These sulphated species eluted at NaCl concentrations of approximately 0 (A), 0.19 (B), 0.34 (C) and 0.78 mol/L (D) from a Q-Sepharose ion exchange column. Further analysis by size exclusion chromatography and chemical and enzymatic digestion showed that peaks B and C had molecular weights of 2.4 x 10(5) and 2.8 x 10(5), respectively and were resistant to chondroitinase ABC, heparitinase and nitrous acid digestion. Peak D was found to contain a polydisperse population of molecules with a molecular weight range of approximately 1 x 10(4) to 6 x 10(4). This sample was susceptible to nitrous acid and chondroitinase ABC digestion and was found predominantly in the sample isolated from deeper in the tissue. We have thus developed an in vivo labelling technique for sulphated macromolecules that can be used in the further study of injury to the gastric mucosa. PMID- 7787158 TI - Colonic mucosal antioxidant enzymes and lipid peroxide levels in normal subjects and patients with ulcerative colitis. AB - Oxygen-derived free radicals have been implicated in the pathogenesis of ulcerative colitis. Mammalian tissues contain antioxidant systems that offer protection from the damaging effect of these active species. In the present study, the activity of the antioxidant enzymes catalase, glutathione peroxidase, glutathione transferase and glutathione reductase were measured in rectal biopsies from patients with ulcerative colitis and compared with that obtained from normal subjects. A significant decrease in the activity of glutathione transferase was observed in ulcerative colitis (48.32 +/- 6.73 units/mg protein, mean +/- s.e.) compared to normal (68.20 +/- 6.83; P = 0.015). There was no difference in the activity of other antioxidant enzymes between controls and ulcerative colitis. Myeloperoxidase, a marker for neutrophil infiltration, was considerably increased in ulcerative colitis while malonaldehyde, the end product of lipid peroxidation, was not increased. The reduced activity of glutathione transferase in ulcerative colitis may be an additional factor in the pathogenesis of mucosal damage in this disease. PMID- 7787161 TI - Immunoglobulin G subclass distribution of human anticolon antibodies in ulcerative colitis. AB - Immunoglobulin G (IgG) subclasses of anticolon antibodies were studied in patients with ulcerative colitis (UC) using enzyme-linked immunosorbent assay (ELISA). The concentrations of total serum IgG subclasses were also measured by ELISA. The values for total serum IgG subclasses in patients with UC were not significantly different from those in normal controls, while the ratio of IgG1 to IgG2 in the patients was significantly higher than that in normal controls. All four IgG subclasses of autoantibodies were demonstrated in the sera of the patients. IgG4 anticolon antibodies were detected most frequently (15 out of 18 patients, 83%). IgG2 was the next most prevalent (9 of 18 patients, 50%). The activity of anticolon antibodies in each subclass did not correlate with the concentration of the corresponding serum IgG subclass. Seven cell lines producing anticolon antibodies were obtained from the colonic mucosa of the patients by Epstein-Barr virus (EBV) transformation. IgG subclasses of anticolon antibodies secreted by these cell lines were also varied. IgG4 subclass was secreted by three EBV transformed cell lines, all of which produced IgG4 anticolon antibodies. These results suggest that all four different IgG subclasses could respond to the colon antigens and that various antigens in colonic mucosa or lumen may contribute to the induction of those autoantibodies. In addition, the prominence of IgG4 anticolon antibodies may support the pathogenic role of this subclass in UC as in other autoimmune diseases. PMID- 7787162 TI - Plasma kallikrein clearance by the liver of chronic carbon tetrachloride-treated rats. AB - We have previously reported that the endocytosis of rat plasma kallikrein (RPK) by hepatocytes is a calcium-independent and beta-galactoside-dependent mechanism. We now report the clearance of RPK by the liver of four groups of rats: normal, inflamed (48 h ex-turpentine) and two groups chronically treated with CCl4 (52 mg/kg per week, intragastrically, for 9-12 weeks). Each liver was isolated, exsanguinated and perfused at 37 degrees C with 30 mL of BSA-Krebs-Henseleit bicarbonate medium containing 10 nmol/L RPK. Although all rats received the same mild CCl4 treatment, the liver histology showed that they evolved either to severe hepatitis (serum alanine aminotransferase [ALT] 4852 +/- 885 U/L, parenchymatous necrosis in the perivenous region) or to compensated cirrhosis (serum ALT 209 +/- 42 U/L, vigorous fibrous encircling regeneration nodules); neither jaundice nor ascites was noted. The results show that serum albumin was not altered among the groups and that: the acute-phase response by itself (inflamed group) increased RPK clearance rate (3.01 +/- 0.59 mL/min) as compared with the normal group (1.85 +/- 0.14 mL/min); the CCl4 treatment, although induced an acute-phase response, decreased (P < 0.01) RPK clearance rates (0.80 +/- 0.11 mL/min hepatitis group and 0.98 +/- 0.10 mL/min cirrhosis group). These findings suggest that the hepatic clearance rate of plasma kallikrein is an early indicator of liver injury. PMID- 7787160 TI - Correlation between serum pepsinogen concentration and gastric acidity measured by 24 h pH monitoring. AB - The relationship between the intragastric pH measured by 24 h pH monitoring system and the serum pepsinogen I/II ratio was studied in 68 cases. When pepsinogen I/II ratio was compared with pH 3.0 holding time (the percentage time during which the gastric pH is above 3.0), there was a negative correlation between these two parameters (correlation coefficient r = -0.62, P < 0.001). Furthermore, there was also a strong negative correlation between the early morning (from 03.00 to 06.00 h) gastric pH and pepsinogen I/II ratio (r = -0.76, P < 0.001). Accordingly, by simply measuring serum pepsinogen I and II, it may be possible to infer gastric acidity and to obtain the information concerning the early morning intragastric pH. PMID- 7787164 TI - Carbohydrate-deficient transferrin in alcoholics with liver disease. AB - To assess the relationship between carbohydrate-deficient transferrin (CDT) and alcoholic liver disease, we measured the ratio of carbohydrate-deficient transferrin to total transferrin (rCDT) in 32 male alcoholics with liver disease (Child-Pugh class A, 8; B, 11; C, 13) and 14 male alcoholics without clinically evident liver disease. Twenty of 32 with liver disease and six of 14 without clinically apparent liver disease had recent abstinence. The 32 patients with liver disease were assessed, in addition to the Child-Pugh class, using a linear prognostic score, the Combined Clinical and Laboratory Index (CCLI). Transferrin and CDT were measured by isocratic anion exchange chromatography and a radio immunoassay. When the total group (n = 46) was divided into those with recent abstinence (n = 26) and those without (n = 20), the rCDT was lower in the abstainers than non-abstainers (0.7 +/- 0.6 vs 2.9 +/- 2.4, P < 0.005). Similarly, abstainers with liver disease (n = 20) had a significantly lower rCDT than non-abstainers (n = 12) with liver disease (0.7 +/- 0.7 vs 3.5 +/- 2.8, P < 0.005). The rCDT in the 20 abstaining patients with liver disease did not differ significantly between Child-Pugh classes. Furthermore, there was no correlation between the CCLI and rCDT (r = 0.05). We conclude that the relationship between rCDT and alcohol abuse is not appreciably altered by the presence of clinically severe liver disease in male alcoholics. PMID- 7787163 TI - A non-invasive method for evaluating cirrhotic portal hypertension by administration of 99mTc-MIBI per rectum. AB - A study was performed to evaluate radio-isotopic imaging using technetium-99m hexakis 2-methoxyisobutyl isonitrile administered per rectum to assess portal collateral circulation. The heart-liver ratios (H/L; mean +/- standard deviation) in 15 controls, 13 cases of histologically confirmed viral hepatitis and 57 cirrhosis patients were 0.27 +/- 0.11, 0.43 +/- 0.14 and 1.00 +/- 0.28, respectively (P < 0.001). Among the cirrhosis patients those with the Child-Pugh classification A, B and C had H/L of 0.56 +/- 0.14, 1.00 +/- 0.20 and 1.19 +/- 0.26, respectively (P < 0.001). A high value of H/L was associated with a high risk of hepatic encephalopathy (1.25 +/- 0.17, P < 0.01) and oesophageal varices (1.02 +/- 0.20, P < 0.01). There were associations between H/L and serum bilirubin (P < 0.01), albumin (P < 0.05) and prothrombin time (P < 0.05). The results also showed a good correlation between H/L and portal vein pressure measured during operation in 13 patients (P < 0.001, r = 0.87). The regression equation: y = 6.77 + 32.5 H/L, allowed portal vein pressure to be estimated. The prognostic value of the test was supported by the fact that good correlations were observed between the H/L ratio and widely accepted prognostic classification (Child-Pugh). It is suggested that this new method could be a reliable non invasive way to give an indication of the degree of portasystemic shunting to evaluate the prognosis and to follow up the effects of medications for reducing portal hypertension in patients with cirrhotic portal hypertension. PMID- 7787166 TI - Hepatitis B vaccination alone is not adequate for the categorizing of adult subjects with isolated anti-HBc. AB - To evaluate the meaning of isolated antibody to hepatitis B core antigen (anti HBc), 88 Chinese subjects with isolated anti-HBc received rescreening of hepatitis B virus (HBV) markers. Eighty (90.9%) of them were still positive for this antibody and 29 were also found to be positive for antibody to hepatitis B surface antigen (anti-HBs). The remaining 51 subjects (58.0%) were positive for anti-HBc alone; 50 of them received a four-dose schedule of hepatitis B (HB) vaccine. After the initial dose, only one vaccinee disclosed an amnestic anti-HBs response, that is, anti-HBs titre > 1000 miu/mL. Forty-five vaccinees completed the vaccination schedule and 44 (97.8%) had anti-HBs response. The anti-HBs responses in 25 of these vaccinees were compared with 25 age- and sex-matched normal susceptible vaccinees. The anti-HBs response rates in both groups were the same (96 vs 96%). However, the geometric mean titre was significantly lower in the vaccinees with isolated anti-HBc (512 mIU/mL vs 4688 mIU/mL, P < 0.001). Prevaccinated sera were available in 49 vaccinees with isolated anti-HBc for detection of antibody to hepatitis B e antigen (anti-HBe) and HBV DNA; 37 (75.5%) of them had one or two of these markers. As we regarded the rescreening of HBV markers, response to hepatitis B vaccination and presence or absence of anti-HBe and/or HBV DNA together for categorizing the 88 subjects with isolated anti-HBc, at least three-quarters of them had past infection of HBV. The subjects with false positive anti-HBc test were a minor group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787165 TI - Influence of ascites on the chemotaxis of granulocytes in patients with cirrhosis. AB - Spontaneous bacterial peritonitis is a specific infectious complication in liver cirrhosis. The reasons for the preferred location of infection on the peritoneum are not clear. The aims of the present study were to ascertain whether hepatogenic ascites fluid is chemotactically effective, what part is played by complement factor C3 and whether there are inhibitors of chemotaxis in ascites. Chemotaxis of granulocytes in serum and ascites fluid was measured in 18 patients with cirrhosis and ascites and in 18 healthy individuals using the Boyden chamber method. In the patients, the chemotactic effect of serum was reduced significantly. Ascites fluid had lower chemotactic activity than autologous serum (P < 0.01), directly correlated to C3 levels (P < 0.025). There was a significant correlation between chemotaxis in serum and in ascites fluid (P < 0.005). Adding ascites fluid to serum led to reduction of chemotactic activity only in the patients (P < 0.025). In conclusion, the chemotactic effect of ascites fluid is considerably lower than that of serum and is proportional to local concentrations of C3. Chemotaxis-inhibiting factors can also be identified in ascites fluid, their pathogenetic relevance being limited. PMID- 7787168 TI - Nizatidine and acid-pepsin related gastrointestinal disease. PMID- 7787167 TI - Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis. AB - We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vasodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease. PMID- 7787169 TI - A radical perspective on ulcerative colitis. PMID- 7787170 TI - Sulphation of proteoglycans and intestinal function. PMID- 7787171 TI - Twenty-four hour pH monitoring and serological parameters of gastric secretion. PMID- 7787172 TI - The role of gastrin and cholecystokinin in normal and neoplastic gastrointestinal growth. AB - Gastrin and cholecystokinin (CCK) act as growth factors for the gastric mucosa and the pancreas, respectively. CCK is also responsible, via the CCK-A receptor, for the pancreatic hyperplasia observed following the feeding of protease inhibitors or pancreaticobiliary diversion. Hypergastrinaemia does not increase the incidence of spontaneous gastrointestinal carcinoma, but does stimulate the proliferation of gastric enterochromaffin-like cells via the gastrin/CCK-B receptor, with a consequent increase in the incidence of gastric carcinoids. Whether gastrin influences mutagen-induced gastrointestinal carcinogenesis is still controversial, but CCK clearly enhances the induction by carcinogens of acinar tumours in the pancreas. While gastrin increases xenograft growth of 50% of gastrointestinal tumours tested, effects on the proliferation of gastrointestinal tumour cell lines in vitro have been more difficult to demonstrate, perhaps because many cell lines are already maximally stimulated by autocrine gastrin. Gastrin mRNA and progastrin, but not mature amidated gastrin, have been detected in all gastrointestinal cell lines tested. Although cell proliferation is inhibited by gastrin/CCK receptor antagonists, the spectrum of antagonist affinities is not consistent with binding to either CCK-A or gastrin/CCK-B receptors. Definition of the molecular structure of the receptor involved in the autocrine loop may lead to novel therapies for gastrointestinal cancer. PMID- 7787173 TI - Successful in vitro fertilization and pregnancy in a patient with autoimmune chronic active hepatitis and cirrhosis. AB - Fertility is reduced in women with chronic active autoimmune hepatitis (AIH) and pregnancy is hazardous. This report describes a 33 year old woman with AIH and cirrhosis in whom a successful pregnancy was achieved following in vitro fertilization/embryo transfer. Disease exacerbation during pregnancy was controlled by azathioprine and an increased dose of prednisone, and a healthy child was delivered by Caesarean section at 36 weeks gestation. Since the perinatal care of preterm infants and the obstetric care available to women with complicated medical problems has improved markedly in recent years and since active disease can be controlled by adequate immunosuppressive therapy, we propose that it is justified to allow these patients access to in vitro fertilization programmes. PMID- 7787175 TI - Molecular cloning and characterization of a pea chitinase gene expressed in response to wounding, fungal infection and the elicitor chitosan. AB - The fungicidal class I endochitinases (E.C.3.3.1.14, chitinase) are associated with the biochemical defense of plants against potential pathogens. We isolated and sequenced a genomic clone, DAH53, corresponding to a class I basic endochitinase gene in pea, Chi1. The predicted amino acid sequence of this chitinase contains a hydrophobic C-terminal domain similar to the vacuole targeting sequences of class I chitinases isolated from other plants. The pea genome contains one gene corresponding to the chitinase DAH53 probe. Chitinase RNA accumulation was observed in pea pods within 2 to 4 h after inoculation with the incompatible fungal strain Fusarium solani f. sp. phaseoli, the compatible strain F. solani f.sp. pisi, or the elicitor chitosan. The RNA accumulation was high in the basal region (lower stem and root) of both fungus challenged and wounded pea seedlings. The sustained high levels of chitinase mRNA expression may contribute to later stages of pea's non-host resistance. PMID- 7787174 TI - Features of the hmg 1 subfamily of genes encoding HMG-CoA reductase in potato. AB - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes a key step in isoprenoid metabolism leading to a range of compounds that are important for the growth, development and health of the plant. We have isolated 7 classes of genomic clones encoding HMGR from a potato genomic library. Comparison of nucleic acid sequences reveals a high degree of identity between all seven classes of clones and the potato hmg 1 gene described by Choi et al. (Plant Cell 4: 1333, 1992), indicating that all are members of the same subfamily in potato. A representative member (hmg 1.2) of the most abundant class of genomic clones was selected for further characterization. Transgenic tobacco and potato containing the beta-glucuronidase (GUS) reporter gene under the control of the hmg 1.2 promoter expressed GUS activity constitutively at a low level in many plant tissues. High levels of GUS activity were observed only in the pollen. GUS assays of isolated pollen, correlations of GUS activity with the HMGR activity of anthers, hmg 1.2 promoter deletion studies, and segregation analysis of the expression of hmg 1.2::GUS among the R2 pollen of R1 progeny plants demonstrated that the hmg 1.2 promoter controls pollen expression. PMID- 7787176 TI - Characterization of cDNA clones for differentially expressed genes in embryos of dormant and nondormant Avena fatua L. caryopses. AB - The molecular regulation of seed dormancy was investigated using differential display to visualize and isolate cDNAs representing differentially expressed genes during early imbibition of dormant and nondormant Avena fatua L. embryos. Of about 3000 cDNA bands examined, 5 cDNAs hybridized with mRNAs exhibiting dormancy-associated expression patterns during the first 48 h of inhibition, while many more nondormancy-associated cDNAs were observed. Dormancy-associated clone AFD1 hybridized with a 1.5 kb mRNA barely detectable in dry dormant and nondormant embryos that became more abundant in dormant embryos after 24 h of imbibition. Clone AFD2 hybridized with two mRNAs, a 1.3 kb message constitutively expressed in dormant and nondormant embryos and a 0.9 kb message present at higher levels in dormant embryos after 3 h of imbibition. Nondormancy-associated clones AFN1, AFN2 and AFN3 hybridized with 1.5 kb, 1.7 kb and 1.1 kb mRNAs, respectively, that were more abundant in nondormant embryos during imbibition. Expression patterns of some mRNAs in dormant embryos induced to germinate by GA3 treatment were different than water controls, but were not identical to those observed in nondormant embryos. DNA sequence analysis revealed 76% sequence identity between clone AFN3 and a Citrus sinensis glutathione peroxidase-like cDNA, while significant sequence similarities with known genes were not found for other clones. Southern hybridization analyses showed that all clones represent low (1 to 4) copy number genes. PMID- 7787177 TI - Expression of Agrobacterium rhizogenes auxin biosynthesis genes in transgenic tobacco plants. AB - Plant oncogenes aux1 and aux2 carried by the TR-DNA of Agrobacterium rhizogenes strain A4 encode two enzymes involved in the auxin biosynthesis pathway in transformed plant cells. The short divergent promoter region between the two aux coding sequences contains the main regulatory elements. This region was fused to the uidA reporter gene and introduced into Nicotiana tabacum in order to investigate the regulation and the tissue specificity of these genes. Neither wound nor hormone induction could be detected on transgenic leaf discs. However, phytohormone concentration and auxin/cytokinin balance controlled the expression of the chimaeric genes in transgenic protoplasts. The expression was localised in apical meristems, root tip meristems, lateral root primordia, in cells derived from transgenic protoplasts and in transgenic calli. Histological analysis showed that the expression was located in cells reactivated by in vitro culture. Experiments using cell-cycle inhibitors such as hydroxyurea or aphidicolin on transgenic protoplast cultures highly decreased the beta-glucuronidase activity of the chimaeric genes. These results as well as the histological approach suggest a correlation between expression of the aux1 and aux2 genes and cell division. PMID- 7787178 TI - A corm-specific gene encodes tarin, a major globulin of taro (Colocasia esculenta L. Schott). AB - A gene encoding a globulin from a major taro (Colocasia esculenta L. Schott) corm protein family, tarin (G1, ca. 28 kDa) was isolated from a lambda Charon 35 library, using a cDNA derived from a highly abundant corm-specific mRNA, as probe. The gene, named tar1, and the corresponding cDNA were characterized and compared. No introns were found. The major transcription start site was determined by primer extension analysis. The gene has an open reading frame (ORF) of 765 bp, and the deduced amino acid sequence indicated a precursor polypeptide of 255 residues that is post-translationally processed into two subunits of about 12.5 kDa each. The deduced protein is 45% homologous to curculin, a sweet-tasting protein found in the fruit pulp of Curculigo latifolia and 40% homologous to a mannose-binding lectin from Galanthus nivalis. Significant similarity was also found at the nucleic acid sequence level with genes encoding lectins from plant species of the Amaryllidaceae and Lilliaceae families. PMID- 7787179 TI - A GCC element and a G-box motif participate in ethylene-induced expression of the PRB-1b gene. AB - The PRB-1b gene codes for a basic-type pathogenesis-related protein and is activated at the transcriptional level by the plant hormone ethylene. To identify cis-acting DNA elements essential for ethylene induction, deleted and mutant forms of the PRB-1b promoter, fused to the beta-glucuronidase (GUS) coding region, were introduced in transgenic tobacco plants. A 73 bp fragment (X1 region) of the PRB-1b promoter, located between positions -213 and -141, was sufficient to confer ethylene responsiveness to the reporter gene. The X1 region contains a TAAGAGCCGCC motif (GCC-box) well conserved in several ethylene inducible genes. A substitution mutation in this sequence, in the context of a 213 bp PRB-1b promoter, completely abolished ethylene induction in transgenic tobacco, defining this conserved motif as part of a cis-acting element responsive to ethylene. Three other mutations in the X1 region caused a pronounced decrease in the PRB-1b promoter activity in transgenic plants, but did not affect ethylene inducibility. One of them, localized in a G-box like motif (CACGTG), disrupted the binding site for a nuclear factor, as observed in gel-shift analysis. Interestingly, the mobility of the complex formed on the G-box element was dependent on its phosphorylation state. These results suggest that a cis-acting element involved in the perception of the ethylene signal resides in a GCC motif and acts in concert with additional elements in the regulation of ethylene induced PRB-1b expression. PMID- 7787181 TI - Expression of three osmotin-like protein genes in response to osmotic stress and fungal infection in potato. AB - We have characterized three cDNAs encoding osmotin-like proteins from potato (Solanum commersonii) cell cultures. These cDNAs (pA13, pA35, and pA81) have extensive nucleotide identity in the coding regions but low homology in the 3' non-coding sequences, and may encode three isoforms of potato pathogenesis related (PR) type 5 proteins. Using gene-specific probes, RNA gel blot analyses showed constitutive accumulation of osmotin-like protein mRNAs in cell cultures, leaves, stems, roots and flowers, with high abundance in the roots and mature flowers. Treatments with abscisic acid (ABA), low temperature, and NaCl increased the accumulation of all three mRNAs in S. commersonii cell cultures and plants grown in vitro. Salicylic acid (SA), and wounding resulted in a moderate increase in the levels of pA13 and pA81 but not pA35 mRNAs. Infection with the fungus Phytophthora infestans activated strong and non-systemic expression of all three osmotin-like protein genes. The accumulation of osmotin-like proteins, however, was detected only in P. infestans-infected tissues but not in plants treated with ABA, SA, NaCl, low temperature, or wounding. PMID- 7787180 TI - Structural and functional characterization of two wheat histone H2B promoters. AB - Two wheat histone H2B genes (TH123 and TH153) were isolated. Nucleotide sequence analysis revealed that some characteristic sequence motifs were conserved in both the 5'- and 3'-flanking regions. A canonical TATA box and several CCAAT sequences were present in the presumed promoter regions. Motifs similar or identical to the hexamer (ACGTCA) and octamer (CGCGGATC) motifs that are positive cis-acting elements of the wheat H3 (TH012) promoter were also observed in both the H2B promoters. A gel mobility shift assay indicated that the hexamer and hexamer-like motifs bound the wheat bZIP proteins HBP-1a and/or HBP-1b in vitro. A novel sequence motif, (A/T)(G/A)AAAT(A/G), was found downstream of a translational stop codon as observed in several plant histone H2B cDNAs. Promoter activity was analyzed with H2B promoter-GUS fusion genes in the transient system using tobacco protoplasts. Studies of the promoter function in transgenic tobacco plants showed that the H2B promoters were preferentially active in meristematic tissues. Taken together, our data indicate that the H2B genes are regulated, in part, by the same mechanism as found in H3 and H4 gene transcription. PMID- 7787184 TI - The location of untranscribed DNA sequences within ras genes essential for eliciting plant growth suppression. AB - Three heterologous ras DNA-coding sequences and their deletion derivatives were introduced into plant cells to investigate the role of the ras-coding sequences, especially conserved regions, in eliciting growth inhibition. All three ras coding sequences caused a similar inhibition of plant cell growth, and it was the conserved coding regions which were responsible for this inhibitory effect. The 493 bp conserved region within the v-Ha-ras-coding sequence was studied further, and was shown to be responsible for the inhibitory effect. This region is conserved (over 44%) among the three ras genes studied and encodes a catalytic region of the Ras protein. Small deletions at either the 5' or 3' end of this 493 bp sequence could abolish or dramatically reduce the inhibitory effect. A 36 bp region at the 5' end of the 493 bp region was found to be highly conserved between v-Ha-ras and eight different plant ras or ras-related genes based upon analysis of published sequences. Small deletions affecting this highly conserved 36 bp region completely abolished the inhibitory effect, while deletion of a similar number of base pairs in adjacent regions did not. These results indicate that plant growth inhibition by ras DNA requires small regions at both ends of the 493 bp conserved region. PMID- 7787183 TI - Structural organization and differential expression of carrot beta fructofuranosidase genes: identification of a gene coding for a flower bud specific isozyme. AB - Three genomic clones (Inv*Dc1, Inv*Dc2 and Inv*Dc3) were isolated by using the cDNA for carrot cell wall beta-fructofuranosidase as a probe. The expression patterns of the three genes differed markedly. High levels of Inv*Dc1 transcripts were found in leaves and roots of young carrot, whereas in plants with developing tap roots no transcripts were detected. A high level of mRNA of Inv*Dc1 was also present in suspension-cultured cells. In developing reproductive organs, only low levels of transcripts of Inv*Dc1 were found in flower buds and flowers and none at later stages of development. In contrast, Inv*Dc2 and Inv*Dc3 were not expressed in vegetative plant organs. Invb1*Dc1 was exclusively and strongly expressed in flower buds, and Inv*Dc3 at a very low level in suspension-cultured cells. PMID- 7787182 TI - The NADP-glutamate dehydrogenase of the cyanobacterium Synechocystis 6803: cloning, transcriptional analysis and disruption of the gdhA gene. AB - The gdhA gene of Synechocystis PCC 6803, which encodes an NADP-dependent glutamate dehydrogenase (NADP-GDH), has been cloned by complementation of an Escherichia coli glutamate auxotroph. This gene was found to code for a polypeptide of 428 amino acid residues, whose sequence shows high identity with those of archaebacteria (42-47%), some Gram-positive bacteria (40-44%) and mammals (37%). The minimal fragment of Synechocystis DNA required for complementation (2kb) carries the gdhA gene preceded by an open reading frame (ORF2) encoding a polypeptide of 130 amino acids. ORF2 and gdhA are co transcribed as a 1.9 kb mRNA, but shorter transcripts including only gdhA were also detected. Two promoter regions were identified upon transcriptional fusion to the cat reporter gene of a promoter probe plasmid. Transcription from the promoter upstream of ORF2 was found to be regulated depending on the growth phase of Synechocystis, in parallel to NADP-GDH activity. This promoter is expressed in Escherichia coli too, in contrast to the second promoter, located between ORF2 and gdhA, which was silent in E. coli and did not respond to the stage of growth in Synechocystis. Disruption of the cyanobacterial gdhA gene with a chloramphenicol resistance cassette yielded a mutant strain totally lacking NADP GDH activity, demonstrating that this gene is not essential to Synechocystis 6803 under our laboratory conditions. PMID- 7787185 TI - Identification and characterization of genes with unstable transcripts (GUTs) in tobacco. AB - Plants and other higher eukaryotes have the ability to recognize and target specific transcripts for rapid decay from among the majority of relatively stable mRNAs present within cells. However, little is known about the nature of unstable transcripts in plants, or the mechanisms that facilitate their rapid degradation. As a first step toward understanding how plants distinguish between unstable and stable transcripts, a novel differential screen was used to identify cDNAs for genes with unstable transcripts (GUTs), solely on the basis of the instability of their mRNAs. cDNA probes were prepared from tobacco cells that had been depleted of highly unstable mRNAs by treatment for 90 min with a transcriptional inhibitor, and from control, untreated cells. GUT clones were selected on the basis of weak hybridization to the former probe relative to the latter probe. Half-life measurements performed on the mRNAs hybridizing to eight GUT clones indicated that each was unstable, with a half-life on the order of about an hour or less. All eight of the cDNAs corresponded to new tobacco genes, and four showed sequence similarity with genes from other species, including the eukaryotic family of DNAJ homologs, a tomato wound-inducible protein, and histone H3. In addition to providing information about the types of transcripts that are inherently unstable in plants, the GUT clones should provide excellent tools for the identification of cis- and trans-acting determinants of mRNA instability. PMID- 7787186 TI - Isolation of a carrot gene expressed specifically during early-stage somatic embryogenesis. AB - We report the first successful isolation by subtractive hybridization of a gene expressed specifically during somatic embryogenesis. Embryogenic cell clusters, 32-50 microns in diameter, were isolated by sieving and density-gradient centrifugation. The cDNA library was constructed from proglobulars which were formed from embryogenic cell clusters 3 days after transfer to auxin-free modified Lin and Staba's medium. For use as probe in screening, the same cDNA used for library construction was enriched for specific sequences using subtractive hybridization. The cDNA used for subtraction was prepared from suspension cultures 5 days after subculturing in auxin-containing medium. Nine independent differentially expressed cDNA clones were obtained from a screen of 150,000 recombinant phages. Northern analysis indicated one of these, CEM6, to be expressed specifically during somatic embryogenesis. In addition, one hybridizing transcript was detected in plantlet cotyledons, and two transcripts were detected in hypocotyls. Two separate and distinct hybridizing transcripts are expressed specifically in hypocotyl tissue. The amino acid sequence deduced from the nucleotide sequence of the CEM6 cDNA indicates that it encodes a glycine-rich protein containing a hydrophobic signal-sequence like domain. Its early embryo specific expression and sequence characteristics suggest an important role as a cell wall protein in embryogenesis. PMID- 7787188 TI - Narbonin, a novel 2S protein from Vicia narbonensis L. seeds: cDNA, gene structure and developmentally regulated formation. AB - cDNA and genomic clones encoding narbonin, a 2S globulin from the seed of narbon bean (Vicia narbonensis L.), were obtained using the polymerase chain reaction (PCR) and sequenced. The full-length cDNA as well as genomic clones contain a single open reading frame (ORF) of 873 bp that encodes a protein with 291 amino acids comprising the mature narbonin polypeptide (M(r) ca. 33 100) and an initiation methionine. The deduced amino acid sequence lacks a transient N terminal signal peptide. The genomic clones do not contain any intron. No homology was found to nucleic acid and protein sequences so far registered in sequence data libraries. The biosynthesis of narbonin during embryogenesis is developmentally-regulated and its pattern of synthesis closely resembles that of typical seed storage globulins. However, during seed germination narbonin was degraded very slowly, indicating that it may have other function than storage protein. Southern analysis suggests the existence of a small narbonin gene family. Narbonin genes were also found in four different species of the genus Vicia as well as in other legumes such as Canavalia ensiformis and Glycine max. In Escherichia coli a recombinant narbonin was produced which yielded crystals like those prepared from narbonin purified from seeds. PMID- 7787189 TI - Developmental regulation and tissue-specific differences of heat shock gene expression in transgenic tobacco and Arabidopsis plants. AB - The heat shock (hs) response during plant growth and development was analyzed in tobacco and Arabidopsis using chimaeric beta-glucuronidase reporter genes (hs Gus) driven by a soybean hs promoter. Fluorimetric measurements and histochemical staining revealed high Gus activities in leaves, roots, and flowers exclusively after heat stress. The highest levels of heat-inducible expression were found in the vascular tissues. Without heat stress, a developmental induction of hs-Gus was indicated by the accumulation of high levels of Gus in transgenic tobacco seeds. There was no developmental induction of hs-Gus in Arabidopsis seeds. In situ hybridization to the RNA of the small heat shock protein gene Athsp17.6 in tissue sections revealed an expression in heat-shocked leaves but no expression in control leaves of Arabidopsis. However, a high level of constitutive expression of hs genes was detected in meristematic and provascular tissues of the Arabidopsis embryo. The developmental and tissue-specific regulation of the hs response is discussed. PMID- 7787187 TI - Chalcone synthase-like genes active during corolla development are differentially expressed and encode enzymes with different catalytic properties in Gerbera hybrida (Asteraceae). AB - Recent studies on chalcone synthase (CHS) and the related stilbene synthase (STS) suggest that the structure of chs-like genes in plants has evolved into different forms, whose members have both different regulation and capacity to code for different but related enzymatic activities. We have studied the diversity of chs like genes by analysing the structure, expression patterns and catalytic properties of the corresponding enzymes of three genes that are active during corolla development in Gerbera hybrida. The expression patterns demonstrate that chs-like genes are representatives of three distinct genetic programmes that are active during organ differentiation in gerbera. Gchs1 and gchs3 code for typical CHS enzymes, and their gene expression pattern temporally correlates with flavonol (gchs1, gchs3) and anthocyanin (gchs1) synthesis during corolla development. Gchs2 is different. The expression pattern does not correlate with the pigmentation pattern, the amino acid sequence deviates considerably from the consensus of typical CHSs, and the catalytic properties are different. The data indicate that it represents a new member in the large superfamily of chs and chs related genes. PMID- 7787192 TI - The International Classification of Impairments, Disabilities, and Handicaps (ICIDH): perspectives and developments (part I) PMID- 7787190 TI - Expression of the CMS-associated urfS sequence in transgenic petunia and tobacco. AB - The expression of a 25 kDa protein, encoded by the fused mitochondrial pcf gene, is associated with cytoplasmic male sterility (CMS) in petunia. To investigate the role of the 25 kDa protein in CMS we have transformed petunia and tobacco plants with constructs expressing a portion of the urfS sequence of the pcf cDNA which encodes the 25 kDa protein. The urfS sequence was fused with two different mitochondrial targeting sequences. The chimeric gene coding region was placed under the control of the CaMV 35S promoter or a tapetum-specific promoter. Expression of the PCF protein was obtained in mitochondria of transgenic petunia and tobacco plants, yet fertility of the plants was not affected. Analysis of the location of the urfS-encoded protein revealed that it fractionates primarily into the soluble fraction in the transgenic plants whereas the genuine 25 kDa protein is found primarily in the soluble fraction but also in the membrane portion of immature buds from CMS petunia plants. Fertile transgenic plants were obtained which expressed the 25 kDa protein in the tapetal layer of post-meiotic anthers, while CMS plants express the endogenous 25 kDa protein in both the tapetal layer and sporogenous tissue of pre-meiotic anthers. PMID- 7787193 TI - The ICIDH: evolution, status, and prospects. AB - The assessment of disability prevalence in populations is a long-standing concern. In the mid-1970s the World Health Organization (WHO) introduced a scheme for the measurement of the consequences of disease. The classification of the long-term non-fatal consequences of disease is structured on three axes, corresponding roughly to experiences at the level of organ or function (impairment--1009 items), individual action (disability--338 items) and societal interaction (handicap/disadvantage--72 items). The International Classification of Impairments, Disabilities, and Handicaps (ICIDH) is now well established. This paper describes developments in the use of the ICIDH since 1980, in assessing the prevalence of disability in populations, in formulating policy decisions, in management at institution level, and in the care of individuals. It lists problems identified in the use of the ICIDH, such as the need to clarify the role and interrelationship of environmental factors in the definition and development of the different planes addressed by the ICIDH, problems of overlap between disabilities and handicaps, and between impairments and disabilities. Suggestions for improvement include a greater emphasis on presenting handicap as a description of the interrelation between impairments or disabilities and their physical and social environment. It is anticipated that a revised proposal will be finalized for 1998 and formally issued in 1999. PMID- 7787194 TI - Reflection on the definition of impairment and disability as defined by the World Health Organization. AB - The International Classification of Impairments, Disabilities, and Handicaps (ICIDH) is gaining wide acceptance inside and outside the field of rehabilitation medicine. Impairment and disability are concepts which are often used interchangeably or defined differently. The World Health Organization (WHO) has defined impairment and disability in the ICIDH. In this article an analysis is made of these definitions and the characteristics that are given for the definitions. Based on this analysis, modifications for the definitions and characteristics of impairment and disability are suggested. PMID- 7787195 TI - The ICIDH: health problems in a medical and social perspective. AB - The ICIDH is a classification of health problems. Impairments, disabilities, and handicaps are to be considered as three different interpretations of a person's health state. Use of the ICIDH is indicated when a person's health problems need to be described at a particular point in time, both in medical and in social terms, i.e. including their significance for the daily life functioning of the patient. It is argued that the ICIDH is relevant to health problems other than just those for disabled and for chronically ill. The ICIDH subtitle and the model explaining the relations between disease and impairment-disability-handicap do not reflect a clear notion of the perspective of the ICIDH on health problems. An overview of ICIDH applications shows that the ICIDH is being used not so much for the evaluation of the health-care system but for many other purposes, among these the understanding of therapeutic activities. PMID- 7787191 TI - Molecular cloning of an ozone-induced 1-aminocyclopropane-1-carboxylate synthase cDNA and its relationship with a loss of rbcS in potato (Solanum tuberosum L.) plants. AB - Acute or chronic exposure of potato plants to ozone (O3) induces ethylene production. We isolated a 1586 bp cDNA (pOIP-1) encoding 1-aminocyclopropane-1 carboxylate (ACC) synthase from a cDNA library constructed with mRNA extracted from O3-treated leaves. The clone has a 1365 bp open reading frame and a 221 bp trailing sequence. The active site found in all ACC synthases and 11 of the 12 amino acid residues conserved in aminotransferases are found in pOIP-1. Northern analysis showed that the mRNA encoding ACC synthase was detectable 1 h after the onset of O3 exposure, and the message increased over time as did ethylene production. Concurrent with the increased ACC synthase mRNA was a decrease in the message for the Rubisco small subunit (rbcS) with no change in the large subunit (rbcL). When the plants were treated with aminooxyacetic acid (AOA), both ethylene production and level of ACC synthase transcript were inhibited. The decline in rbcS was also inhibited by AOA suggesting a correlation between ethylene production and loss of rbcS. Based on nuclear run-on studies it appears that the increase in ACC synthase mRNA may result from O3-induced transcriptional activity. PMID- 7787196 TI - Human experience in disablement: the imperative of the ICIDH. AB - The ICIDH recognizes that the perspectives of people whose lives are personally shaped by disablement are critical to improving our understanding of disease consequences. However, this 'insider's perspective' has received comparatively little attention in medical research. This article suggests that the weight of medical history mitigates against human experience as a focus of investigation, traces the history of the International Classification of Diseases (ICD) from this perspective, and suggests that these historical influences are still operative in disablement studies. The ICIDH's inclusion of the insider's perspective represents a significant departure from traditional ways of thinking in medical science, and allows for important changes in the discourse about disablement. This article uses phenomenological theory to show how the insider's perspective might be more fully integrated into clinical research and theory development. Finally, this article suggests modifications to the ICIDH that would help to include more explicitly the insider's perspective in its structure. PMID- 7787197 TI - Documenting environmental factors for preventing the handicap creation process: Quebec contributions relating to ICIDH and social participation of people with functional differences. AB - This article presents the conceptual origins and the usefulness of an holistic model, stressing the role of environmental determinants in the performance of day to-day activities and the fulfilment of social roles by persons with disabilities. The Quebec Committee on ICIDH contribution to the development of knowledge on the clarification of the relationship of disabled individual environment and the understanding of the handicap creation process in relation with ICIDH experimentations is presented. Finally, on the basis of anthropological social research conducted in Quebec, the article illustrates a methodology for environmental analysis of the handicap situations of disabled clients in rehabilitation and social integration support programmes. PMID- 7787198 TI - The ICIDH in the USA: applications and relevance to ADA goals. AB - The measurements of disability and environmental barriers have received growing nationwide attention and dissemination in the United States, particularly since the 1990 passage of the Americans with Disabilities Act (ADA). This article presents a brief overview of selected ICIDH uses and applications in the USA. Potential contributions of the ICIDH for ADA implementation are discussed, and parallel definitions of disability in the ICIDH and the ADA are cited. PMID- 7787199 TI - Disability, resources, role demands and mobility handicap. AB - Research on disablement highlights a wide variability in the impact of disabling conditions on individuals' lives. However, in most of this work, the relationships between impairment/disability and features of individuals' social and physical environments are not specified conceptually. Recent conceptual work in the context of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) suggests that the impact of impairment/disability on individuals' lives is contingent on levels of resources and other aspects of social context. The research question addressed in this paper is whether selected social factors affect the impact of impairment/disability on mobility handicap, defined as 'the individual's ability to move about effectively in his/her surroundings'. Two types of social factors are considered: resources such as help from others or having a car available; and social role obligations such as having a job or visiting relatives. Data are derived from a 1986 probability sample of 570 individuals with disabilities living in communities in Calderdale, Yorkshire, England. Multiple-regression models indicate that the impact of walking disability on mobility handicap was reduced by availability of a car in the household and school or job obligations. Other impairments/disabilities, resources and social role demands examined did not act on mobility outcomes in this manner. Implications for conceptualizing and testing relationships between impairment, disability, handicap and social and physical environments are discussed. A critical task for future research is the investigation of personal and social resources and barriers that may moderate the impact of disability on individuals' lives. PMID- 7787200 TI - Rehabilitation Activities Profile: the ICIDH as a framework for a problem oriented assessment method in rehabilitation medicine. AB - The Rehabilitation Activities Profile (RAP) is an ICIDH-based assessment method that covers the domains of communication, mobility, personal care, occupation, and relationships. Disabilities and handicaps in these domains are assessed on four-point Likert scales for severity. Problems perceived by the patient associated with these disabilities or handicaps are also assessed on four-point Likert scales for severity. High scores on perceived problems represent a patient's priorities. Information is gathered through a semi-structured interview with the patient; proxies and observations can be used as additional sources of information. Assessment can be performed at two levels. The first level is a global one, serving as a screening device. If disabilities or handicaps are identified, the second level provides for an in-depth assessment of those specific disabilities and handicaps as well as the related perceived problems. The method is designed to assist screening, goal-setting, and outcome evaluation of individual patients. PMID- 7787201 TI - Using the handicap code of the ICIDH for classifying patients by intensity of nursing care requirements. AB - An 11-class patient classification system (PCS) has been built on a recode of two dimensions of the handicap code of the ICIDH: physical independence and mobility handicaps. The proposed system, called MAC XI, explains 78% of the variance of nursing care hours required by nursing-home residents and extended-care hospital patients. This percentage of variation is higher than the one explained by traditional dependency grids such as the Exton-Smith, Murphy, Kuntzmann and SMAF. MAC XI, based on two dimensions of the handicap code, is thus a powerful tool for predicting intensity of nursing care for staffing and budgeting purposes in long term care institutions. PMID- 7787202 TI - The need for revision of the ICIDH: an example--problems in gait. AB - In this article a proposal is formulated for adjustment of the Classification of Impairments and the Classification of Disabilities of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH). This proposal is a product of a project from the Dutch National Institute of Research and Postgraduate Education in Physical Therapy. This project is conducted in close cooperation with the professional national organizations of five health professions. To give an indication of the kind of changes proposed, the disabilities and impairments necessary for classifying the complaints, the examination findings, the treatment goals and the treatment results in patients with gait problems are discussed. PMID- 7787203 TI - Application of the ICIDH in survey research on rehabilitation: the emergence of the functional diagnosis. AB - The International Classification of Impairments, Disabilities, and Handicaps (ICIDH) has been hypothesized to be an excellent conceptual framework for the functional diagnosis, i.e. the evaluation of health problems by rehabilitation specialists. The ICIDH-based functional diagnosis was assessed in a series of survey studies on physical therapy, exercise therapy, occupational therapy, podiatry, and speech therapy. The results show that the functional diagnosis tends to be reliable; that treatment goals, derived from the diagnosis, offer a sensible characterization of care given by rehabilitation specialists; and that treatment goals validity predict the selection of interventions by rehabilitation specialists. It is concluded that the application of the ICIDH in research on the functional diagnosis is highly appropriate. In future studies the concept of the functional diagnosis and the diagnostic procedures should be further developed. PMID- 7787204 TI - Revision of the ICIDH: mental health aspects. WHO/MNH Disability Working Group. AB - This article reviews the key issues arising in the revision of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) from a mental health perspective, and describes the work of the Disability Working Group of the WHO's Division of Mental Health. The ICIDH, which describes the consequences of disorders at three levels as impairments, disabilities, and handicaps, is generally applicable and useful for mental health purposes. While some impairments are mainly a consequence of 'mental' disorders (e.g. cognitive impairment), there should be no differences between mental and physical disorders in the classification scheme, to avoid a dichotomy between mind and body. There is also a need to improve the ways in which interference with the performance of social roles is described, since this is often the most obvious consequence of mental disorders. This article presents the potentials of the ICIDH in the field of mental health, and gives recommendations for the development of the revision process of the ICIDH. To stimulate the process of producing a 'common language' in the ICIDH related to mental health issues, former and potential users of the ICIDH are invited to give comments and suggestions. PMID- 7787205 TI - Lymphotropism of hepatitis B and C viruses: an update and a newcomer. AB - The mechanisms of viral persistence are complex and include infection of the lymphoid cells. In the case of hepatitis B virus, early observations have suggested that HBV may infect peripheral blood mononuclear cells (PBMC). In animal models studies in chronic hepatitis B patients have further confirmed that viral DNA replicative intermediates, as well as viral transcripts and proteins, can be detected in PBMC under certain conditions. The consequences of this lymphotropism are not fully understood, but it seems likely that PBMC represent an extrahepatic reservoir of virus. The ability of hepatitis C virus to infect PBMC has been demonstrated in vivo and in vitro. The link between HCV lymphotropism and both the natural history of the viral infection and the immunological disorders frequently observed in HCV infections still needs to be established. In both cases, the infection of PBMC by HBV or HCV may represent the source of infection of the liver graft in patients transplanted for end-stage liver disease associated with HBV or HCV. PMID- 7787206 TI - Cytokines as adjuvants in immunocompromised hosts. AB - Vaccination of immunocompromised subjects may be ineffective due to the poor immune responses induced. In addition, vaccination with live attenuated organisms may also be dangerous due to the possible lack of control of the infection. This review describes the protection of cytokines in the vaccination of immunocompromised individuals. Cytokines have possible roles as immunological adjuvants, enhancing immune responses to vaccination, and can also have effects on the growth of live vaccines or vaccine vectors. PMID- 7787207 TI - The role of cytokines in the acquired immunodeficiency syndrome. AB - HIV replication in vitro is regulated by many factors, including various exogeneous stimuli and proteins encoded by either virus or cellular genomes. During the asymptomatic period, cells latently or chronically infected with HIV gradually express virus, leading to immunosuppression and opportunistic infection. These conditions would result in the increased secretion of cytokines, especially TNF, from infected and uninfected cells, which can induce HIV and killing of infected cells. A vicious circle is then set in motion in which heterologous microbial infections directly or indirectly activate HIV and the production of cytokines, thereby accelerating lymphocyte depletion and immunodeficiency. AIDS is a disorder of the immune network caused by a unique retrovirus HIV. However, if the whole story described above is true, this disease can also be termed a "cytokine disease". Immunity resembles a "double-edged sword", with aspects not only protective, but also deleterious to the host. Therefore, it is essential to more extensively investigate the mechanism of cytokine regulation of HIV expression in vivo, not only to understand the complex pathophysiology of AIDS, but also to design a therapeutic strategy to halt this deadly disease. PMID- 7787208 TI - Detection of hepatitis D virus RNA in serum by a reverse transcription, polymerase chain reaction-based assay. AB - We designed a reverse transcription, polymerase chain reaction-based assay for serum hepatitis D virus RNA. Amplified hepatitis D virus cDNA was revealed by ethidium bromide staining, followed by blotting onto a nylon membrane and hybridization with a 32phosphorus-labelled oligonucleotide, or by a DNA enzyme immunoassay (DEIA) using a double stranded DNA-specific monoclonal antibody. The absolute sensitivity was expressed as number of hepatitis D virus RNA molecules, using a serum of known viral RNA concentration. Three sets of primers were used, encompassing the base positions 66-686 (variable rod-stabilizing region), 701-962 (conserved, viroid-like domain) and 886-1,333 (portion of the open reading frame 5 encoding for the carboxyterminus of the hepatitis D antigen) of the viral genome. The lower detection limits, after amplification of the three RNA portions, as assessed by ethidium bromide staining, were 7.5 x 10(6), 7.5 x 10(4) and 7.5 x 10(2) molecules of hepatitis D virus RNA per assay, respectively. The region encompassing bases 886-1,333 was chosen for blotting and hybridization to a radiolabelled oligonucleotide probe or for a capture-based DNA enzyme immunoassay, where the microplate was coated with this same probe. The two procedures showed comparable sensitivity, i.e., about 10 molecules of viral RNA per assay. The specificity of the assay was further on a panel of both anti hepatitis D-positive and -negative sera. Amplification of serum hepatitis D virus RNA by reverse transcription/polymerase chain reaction followed by detection of the amplified cDNA by DNA enzyme immunoassay is a promising and feasible routine assay for detecting low amounts of circulating virions. PMID- 7787209 TI - Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. AB - We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread. PMID- 7787210 TI - Orthotopic liver transplantation in a patient with severe hemophilia A: a life saving treatment for the first Italian case. AB - Clinical cure of hemophilia A by orthotopic liver transplantation has been reported in 11 cases. We describe the first successful Italian case. A 27-year old man had cirrhosis caused by previous infections with the hepatitis B, C and D viruses following life-long treatment with factor VIII concentrates made from large plasma pools. He was, however, seronegative for the human immunodeficiency virus. In the year before transplantation, life-threatening gastrointestinal bleeding due to severe esophageal varices required a large transfusion regimen (on average, 13 bags of red cell concentrates and 35,000 U of factor VIII/week). To perform orthotopic liver transplantation 8,000 U of factor VIII were given during surgery together with 10 bags of red cells and 11 of fresh-frozen plasma. Intraoperative bleeding was not different from that of non-hemophilic patients undergoing orthotopic liver transplantation. No additional factor VIII was used after transplantation and factor VIII levels in plasma were always above 50 U/dl, reaching the highest value of 184 U/dl on day 4 post transplantation. He was discharged from hospital 10 weeks after transplantation with factor VIII levels of 68 U/dl. All virological markers are currently negative, except anti-hepatitis C virus antibodies. In this patient orthotopic liver transplantation was a life saving treatment for end-stage cirrhosis and a cure for hemophilia A. PMID- 7787213 TI - International normalized ratio: merits, limits and improvements. PMID- 7787212 TI - Methotrexate therapy and liver fibrosis: are human prolyl hydroxylase and type IV collagen reliable and sensitive markers? PMID- 7787211 TI - Abundance of guanine, guanosine, inosine and adenosine in human seminal plasma. AB - Guanine, guanosine, inosine and adenosine were found in large amounts in seminal plasma from 145 men, regardless of whether spermatozoa were present or not. The mean guanine level in 61 normozoospermic men was 89.7 +/- 93.1 mumol/l; this was significantly lower in 32 vasectomized men (18.9 +/- 31 mumol/l) suggesting the involvement of the epididymis in its secretion. Guanine and nucleoside levels were significantly higher in the seminal plasma of oligozoo- and azoospermic than normozoospermic men. Guanine and nucleoside levels were consistently inter related in the seminal plasma of normozoospermic men with the best correlation between guanine and guanosine. PMID- 7787215 TI - Cholecystokinin in the control of gastric acid and plasma gastrin and somatostatin secretion in healthy subjects and duodenal ulcer patients before and after eradication of Helicobacter pylori. AB - BACKGROUND: Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown. METHODS AND SUBJECTS: In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays. RESULTS: In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin. PMID- 7787214 TI - Ultrastructural analysis of the development of human basophils and mast cells in vitro. AB - The ultrastructural analysis of a variety of culture systems of human cord blood mononuclear cells (spanning a 10-year research effort) is reviewed. Human basophils, eosinophils and mast cells reliably developed from their agranular precursors that are present in human cord blood. Suspension cultures and cocultures with fibroblasts were used to examine the effects on differentiation and maturation of full (fibroblast), interleukin-2-depleted (human T cells), and murine inducer T cell culture supernatants, partially purified mouse fibroblast factor(s), recombinant human interleukins 3 and 5, and recombinant human and murine c-kit ligands (stem cell factor, mast cell growth factor). Together, these studies allowed us to define the differentiation and full maturation of the basophil and eosinophil lineages and provided evidence for the induction of a form of secretion (termed piecemeal degranulation) of the basophil and eosinophil lineages in interleukin-3- or -5-supplemented cultures. Mast cells were absent from interleukin-3- or -5-containing cultures. The development of fully mature mast cells occurred regularly in fibroblast-containing cocultures; partially mature mast cells developed in fibroblast culture supernatant-, partially purified mouse fibroblast factor(s)-, and either recombinant human or murine c kit ligand-supplemented suspension cultures. Small numbers of basophils and eosinophils were present in the suspension cultures that received c-kit ligand in its recombinant or naturally occurring forms. Ultrastructural immunogold analyses confirmed that basophils and eosinophils contained the Charcot-Leyden crystal protein (in different subcellular locations) but that mast cells did not. In both cocultures and suspension cultures, the primary event recorded for mast cells was that of differentiation and maturation, with the ultrastructural correlates of synthetic activity and granule building prevailing. Spontaneous secretory events, recognizable by ultrastructural analysis, were not evident in either mature or partially mature mast cells developing in these cultures. PMID- 7787217 TI - A cost-benefit analysis of feeding in female tsetse. AB - Three models for feeding in female tsetse are considered. Model I: there is a prolonged non-feeding phase after each meal followed by feeding at a constant rate, with a constant probability of dying as a consequence of feeding. Model II: the feeding rate increases linearly after each meal. Model III: the feeding rate increases exponentially after each meal. In Models II and III the feeding hazard is a linear function of the probability of feeding. Production of viable female offspring is estimated under each model, making allowance for losses of adults due to starvation and to background and feeding mortality, losses of pupae due to predation and parasitization, and losses of young flies if their mothers take insufficient blood during pregnancy. Under Model I, if females require three meals to produce viable pupae in 9 days, then for a non-decreasing population with a background mortality of 1%/day, and 25% pupal losses due to predation and parasitism, the feeding risk must be < or = 5%/feed. At this maximum level the non-feeding phase should be 2-2.5 days for optimal productivity, with a mean feeding interval of 60-72 h. If the background mortality is 2%/day, feeding losses cannot exceed 1%/feed for a non-decreasing population. If four or five meals are required for the production of fully viable pupae, the optimal values of the non-feeding phase and mean feeding interval tend towards 1 and 2 days respectively. Under Models II and III the mean feeding interval is 50-60 h for optimal productivity (with variances 3 times as large as for Model I), in good agreement with estimates from recent models for feeding and digestion. Field evidence suggests that feeding tsetse take greater risks as their fat levels dwindle. This should result in feeding (and feeding mortality) rates which increase during the feeding phase--as assumed in Models II and III but not in Model I. These models allow greater flexibility than Model I, because flies can feed early in the hunger cycle, at low probability, as long as the feeding risk is also low. PMID- 7787218 TI - Isolation and characterization of a trypsin-like enzyme from the buffalo fly, Haematobia irritans exigua. AB - The incorporation of soybean trypsin inhibitor (SBTI) into the diet of the buffalo fly, Haematobia irritans exigua (De Meijere), results in increased mortality and reduced fecundity. A trypsin-like enzyme which binds to SBTI was isolated by affinity chromatography on a Sepharose-SBTI column followed by ion exchange chromatography. The enzyme was inhibited by benzamidine, phenylmethylsulfonyl fluoride, ovomucoid, leupeptin and alpha-2 macroglobulin. The enzyme was not inhibited by EDTA or p-chloromecuribenzoic acid and had a broad pH optimum of pH 7-9. Vaccination of sheep produced antibodies specific for the trypsin-like enzyme which inhibited enzyme activity in vitro but did not affect the survival of flies maintained in in vitro culture. PMID- 7787216 TI - Oviposition aggregation pheromone in the Simulium damnosum complex. AB - Communal oviposition by the Simulium damnosum complex of Afrotropical blackflies (Diptera: Simuliidae) was investigated under controlled laboratory conditions, using wild-caught flies in Sierra Leone. Volatile compounds emitted by Simulium eggs were trapped using a closed collection system, and their attractiveness to gravid flies was tested in a two-choice behavioural bioassay. Significantly more female blackflies oviposited on substrates baited with freshly laid eggs (100% chose the baited substrate), or with the volatiles collected from freshly laid eggs (85% chose the baited substrate), in preference to the relevant control substrates. Substrates baited with volatiles from 12-h-old eggs were not significantly more attractive than controls (only 31% chose the baited substrates; P = 0.33). Gas chromatographic analysis of the egg volatiles consistently showed two peaks emanating from fresh eggs, but significantly lower amounts from 12-h-old eggs (P < 0.05). A novel system for collecting the volatiles from this and other blackfly species, as they laid eggs on a substrate in flowing water, is described. Volatiles collected using this method showed identical gas chromatographic profiles to those of fresh eggs alone, indicating that the flies themselves produced no other volatile chemical signals during oviposition. Evidently communal oviposition by S. damnosum s.l. was mediated by a pheromone emanating from fresh eggs. The role of pheromone-mediated egg aggregation in blackfly ecology is discussed, and its possible manipulation is considered. PMID- 7787219 TI - An association between phlebotomine sandflies and aphids in the Peruvian Andes. AB - As the composition of natural sugars in the diet of adult sandflies (Diptera: Psychodidae: Phlebotominae) may affect the development of Leishmania (Kinetoplastida: Trypanosomatidae) in sandfly guts, and so play an important role in the epidemiology of leishmaniasis, there is increasing interest in the sources of sugars for wild sandflies. Advanced chromatography techniques have provided indirect evidence that wild sandflies feed on honeydew, a substance released by aphids (Hemiptera: Aphididae) when feeding. Our objective was to determine whether sandfly density can be influenced directly by the local density of aphids. Aphid density was determined by counting absolute numbers of aphids on alfalfa stems in Purisima Valley, Peru, where sandflies transmit Leishmania peruviana causing Andean cutaneous leishmaniasis (uta). Sandfly relative abundance was measured using sticky trap sampling repeatedly in alfalfa fields. Lutzomyia verrucarum accounted for 92% of the total sandflies collected. As there was a female bias in sandflies collected close to houses, only the numbers of male sandflies were used in analysis. Most of the adult aphids found feeding on alfalfa were either Therioaphis trifolii forma maculata (97%) or Acyrthosiphon pisum (3%). By regression analysis, a significant relationship was found between the density of Lu.verrucarum males and the density of adults of both aphid species. This is the first ecological study to support the hypothesis that aphid honeydew may be a source of sugar for sandflies. PMID- 7787224 TI - Dispersal of the Old World screw-worm fly Chrysomya bezziana. AB - Dispersal of the Old World screw-worm fly, Chrysomya bezziana Villeneuve, was studied in Papua New Guinea by releasing radio-isotope labelled, laboratory reared flies and collecting their labelled egg masses from sentinel cattle. A log linear model was developed to describe recapture rate. Distance was found to dominate the model and was represented by a bilinear ('broken-stick') term as log distance. Further terms in the model such as attractiveness of the site (estimated from the number of non-labelled egg masses), the season of the year and a time trend were statistically significant but of minor importance. From the model, the median distance females dispersed before depositing an egg mass was 10.8 km. The maximum distance from the release site that egg masses were recovered was 100 km. The dispersal ability of C. bezziana is discussed in terms of its impact on the prospects of eradicating this species using SIRM if an outbreak occurred in Australia. PMID- 7787220 TI - Immunosuppression and feeding success of Ixodes ricinus nymphs on BALB/c mice. AB - The effect of repeated infestations of Ixodes ricinus (L.) nymphs on BALB/c mice was studied. Four successive infectations resulted in an increase of tick feeding success. Tick yield and mean engorged weight increased and the length of the feeding period was reduced significantly (P < 0.05-0.01). The increase of specific anti-tick antibodies was not significant (P > 0.05). The blastogenic response of spleen lymphocytes to T-cell mitogens (Con A and PHA-P) was unimpaired or slightly enhanced, whereas the response to B-cell activators (LPS and PWM) was suppressed, as was the total antibody generation in vitro. The numbers of mast cells in murine skin at the tick attachment sites slightly decreased during the third infestation. The suppression of B-cell competence and of antibody generation, together with decrease of skin mast cell numbers in tick attachment sits, are considered to be responsible for enhancement of tick feeding success. PMID- 7787221 TI - Mosquito control in Dar es Salaam. I. Assessment of Culex quinquefasciatus breeding sites prior to intervention. AB - In preparation for a trial polystyrene beads and pyriproxyfen for the control of Culex quinquefasciatus mosquitoes, surveys of their breeding were carried out in two contrasting areas of Dar es Salaam, Mikocheni and Ilala, during the dry season. Sanitation structures (latrines, soakage pits, septic tanks and cess pits) were the most profilic breeding places, totalling 780 in Mikocheni and 1544 in Ilala. Those in Mikocheni were estimated to contain about 1.4 times more mosquito pupae, per site, than in such structures in Ilala. This was both because a higher proportion of sites contained visible water and because sites with water were more likely to contain pupae in Mikocheni. The relative importance of the different types of structure, in terms of productivity, was the same in both areas. Although septic tanks and cess pits made up only 10.5% of the on-site sanitation structures in Ilala, they contained 53% of the total number of pupae in enclosed sites; they were therefore particularly important targets for treatment with polystyrene beads. A survey during the rainy season of sites in Ilala revealed little change in the proportion that were wet, or in the frequency of breeding in those with visible water. The number, type and area of open breeding sites varied greatly between the two study areas. In Mikocheni the area of open breeding sites was 100 times greater than in Ilala, with 97% of the 13,000 m2 being flooded grassland. In Ilala all but four of the sixty-six open breeding sites were puddles of sullage water derived from bathrooms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787223 TI - Relationships between host blood factors and proteases in Glossina morsitans subspecies infected with Trypanosoma congolense. AB - Host blood effects on Trypanosoma congolense establishment in Glossina morsitans morsitans and Glossina morsitans centralis were investigated using goat, rabbit, cow and rhinoceros blood. Meals containing goat erythrocytes facilitated infection in G.m.morsitans, whereas meals containing goat plasma facilitated infection in G.m.centralis. Goat blood effects were not observed in the presence of complementary rabbit blood components. N-acetyl-glucosamine (a midgut-lectin inhibitor) increased infection rates in some, but not all, blood manipulations. Cholesterol increased infection rates in G.m.centralis only. Both compounds together added to cow blood produced superinfection in G.m.centralis, but not in G.m.morsitans. Midgut protease levels did not differ 6 days post-infection in flies maintaining infections versus flies clearing infections. Protease levels were weakly correlated with patterns of infection, but only in G.m.morsitans. These results suggest that physiological mechanisms responsible for variation in infection rates are only superficially similar in these closely-related tsetse. PMID- 7787222 TI - Mosquito control in Dar es Salaam. II. Impact of expanded polystyrene beads and pyriproxyfen treatment of breeding sites on Culex quinquefasciatus densities. AB - In two contrasting areas of Dar es Salaam (Ilala and Mikocheni) all enclosed breeding sites of Culex quinquefasciatus, such as latrines and septic tanks, were treated with a floating layer of expanded polystyrene beads. 7 months later checks in both study areas revealed only one site (from which the polystyrene had been removed during emptying) containing immature stages of Cx quinquefasciatus. Open breeding sites such as areas of flooded land and blocked drains were treated with pyriproxyfen (an insect growth regulator) at a concentration of 0.1 ppm. Emergence of Cx quinquefasciatus adults from these sites was inhibited for 4 weeks during the rainy season and for up to 11 weeks during the dry season. The problem of mosquito breeding sites caused by bathroom sullage water was addressed through a combination of health education and indirect pressure from the Urban Malaria Control Project (UMCP) via local community leaders. Households responsible for these sites were encouraged to eliminate them by diverting the water into an enclosed drainage structure, usually a pit latrine. After two weekly visits 64.7% of households had complied and 93.4% had complied after five visits. 5 months later, only 15.7% had reverted to allowing sullage water to collect into puddles. Densities of Cx quinquefasciatus adults dropped by 76.7% in Mikocheni and by 46.2% in Ilala following intervention, but increased by 84.9% and 25.6% in two untreated comparison areas. The reasons for differential success of the combined interventions in the two treated areas are discussed. PMID- 7787225 TI - Pyrethroid-impregnated hessian curtains for protection against mosquitoes indoors in south India. AB - Hessian curtains impregnated with deltamethrin 50 mg/m2 were hung in the eaves and doorways of eight one-roomed huts in Madurai, Tamil Nadu State, South India. Statistically significant reductions of indoor-resting and man-biting densities of the mosquitoes Anopheles subpictus and Culex quinquefasciatus were observed for 14 weeks, in two field trials. Bioassays on curtains in the field showed over 50% mortality of Cx quinquefasciatus and An.stephensi for up to 8 weeks. The curtains were highly acceptable to the community, and cost approximately Rs.33.15 (US$1.05) for material and Rs.10 ($0.32) for delta-methrin per hut, totalling Rs 53.15 ($1.70) for two impregnations giving 6 months protection. Comparative costs of house-spraying with residual insecticides are estimated as Rs.1.92 ($0.06) for two rounds of DDT at 1 g/m2, or Rs.40 ($1.27) for three rounds of malathion at 2 g/m2. Therefore the relative annual cost of protection using deltamethrin impregnated hessian curtains is 28 x or 1.3 x more than for house-spraying with DDT or malathion, respectively (excluding operational expenditure). PMID- 7787226 TI - Malaria-induced reduction of fecundity during the first gonotrophic cycle of Anopheles stephensi mosquitoes. AB - Anopheles stephensi mosquitoes which had fed upon mice infected with Plasmodium yoelii nigeriensis malaria parasites produced significantly fewer eggs than mosquitoes fed on an uninfected mouse. Fecundity reduction was more pronounced when the bloodmeal contained malaria gametocytes and the mosquitoes developed oocysts. Egg production and haematin excretion were correlated for uninfected bloodfed mosquitoes; the presence of P.y.nigeriensis in the blood affected this relationship. Reduced fecundity was associated with a significant reduction of bloodmeal size (measured by haematin excretion) in mosquitoes which ingested gametocytaemic blood. The bloodmeal size in mosquitoes fed on parasitaemic blood without gametocytes was not significantly reduced. The use of haematin assays for determination of bloodmeal size in mosquitoes is discussed. PMID- 7787227 TI - Anopheles culicifacies in Baluchistan, Iran. AB - Anopheles culicifacies (probably species A) is the main vector of malaria in Baluchistan, southeastern Iran. Adult mosquitoes were collected during 1990-92 by five methods of sampling: knock-down pyrethrum space-spray indoors, human and animal bait (18.00-05.00 hours), pit shelters and CDC light traps, yielding 62%, 3%, 6%, 4% and 25% of specimens, respectively. Whereas spray-catches comprised c. 70% gravid and semi-gravid females, light trap catches were mostly (c. 60%) unfed females, while females from pit shelters comprised all abdominal stages more equally (13-36%). An.culicifacies populations peaked in April-May and rose again during August-November. Densities of indoor-resting mosquitoes were consistently greater in an unsprayed village than in villages subjected to residual house spraying with propoxur, malathion or pirimiphos-methyl. Monthly malaria incidence generally followed fluctuations of An.culicifacies density, usually with a peak in May-June. PMID- 7787229 TI - Simulium metallicum cytospecies E larval habitat characterization in the Altamira focus of onchocerciasis, northern Venezuela. AB - Simulium metallicum sibling species E was identified cytotaxonomically from an onchocerciasis focus at Altamira in northern Venezuela. S. metallicum E larvae were sampled monthly from two small mountain streams over a 15-month period (July 1990 to September 1991) and eleven habitat variables were measured at two altitudes. One stream consistently harboured much higher densities of S. metallicum E larvae than the other, with three annual peaks of abundance: during the dry season and at the beginning and end of the rainy season. These peak densities were correlated with high rainfall 4 months previously. Larvae were most abundant on submerged rocks and fallen leaves, in small shallow areas characterized by slow water current, high conductivity and sparse terrestrial vegetation cover. Stream variables which best explained the temporal changes in abundance were water discharge and conductivity. The population dynamics of S. metallicum E appeared to be influenced primarily by interactions between stream discharge and substrate stability. Relevance of these results to vector control with larvicides is discussed. PMID- 7787228 TI - Low-volume application by mist-blower compared with conventional compression sprayer treatment of houses with residual pyrethroid to control the malaria vector Anopheles albimanus in Mexico. AB - Village-scale trials were carried out in southern Mexico to compare the efficacy of indoor-spraying of the pyrethroid insecticide lambda-cyhalothrin applied either as low-volume (LV) aqueous emulsion or as wettable-powder (WP) aqueous suspension for residual control of the principal coastal malaria vector Anopheles albimanus. Three indoor spray rounds were conducted at 3-month intervals using back-pack mist-blowers to apply lambda-cyhalothrin 12.5 mg a.i./m2 by LV, whereas the WP was applied by conventional compression sprayer at a mean rate of 26.5 mg a.i./m2. Both treatments caused mosquito mortality indoors and outdoors (collected inside house curtains) as a result of contact with treated surfaces before and after feeding, but had no significant impact on overall population density of An. albimanus resting indoors or assessed by human bait collections. Contact bioassays showed that WP and LV treatments with lambda-cyhalothrin were effective for 12-20 weeks (> 75% mortality) without causing excito-repellency. Compared to the WP treatment (8 houses/man/day), LV treatment (25 houses/man/day) was more than 3 times quicker per house, potentially saving 68% of labour costs. This is offset, however, by the much lower unit price of a compression sprayer (e.g. Hudson 'X-pert' at US$120) than a mist-blower (e.g. 'Super Jolly' at US$350), and higher running costs for LV applications. It was calculated, therefore, that LV becomes more economical than WP after 18.8 treatments/100 houses/10 men at equivalent rates of application, or after 7.6 spray rounds with half-rate LV applications. PMID- 7787230 TI - A comparison of susceptibility to stocks of Trypanosoma vivax of Glossina pallidipes from allopatric populations in Kenya. PMID- 7787231 TI - Borreliae in larval Ixodes ricinus ticks. PMID- 7787232 TI - Evaluation of host-targeted applications of permethrin for control of Borrelia infected Ixodes ricinus (Acari: Ixodidae). PMID- 7787233 TI - A cytoplasmic polyhedrosis virus in the phlebotomine sandfly Lutzomyia longipalpis. PMID- 7787234 TI - The use of an enhanced ELISA method for the identification of Culicoides bloodmeals in host-preference studies. PMID- 7787235 TI - Muscle-specific gene expression during myogenesis in the mouse. AB - Over the past decade, significant advances in molecular biological techniques have substantially increased our understanding of in vivo myogenesis, supplementing the information that previously had been obtained from classical embryological and morphological studies of muscle development. In this review, we have attempted to correlate morphogenetic events in developing murine muscle with the expression of genes encoding the MyoD family of myogenic regulatory factors and the contractile proteins. Differences in the pattern of expression of these genes in murine myotomal and limb muscle are discussed in the context of muscle cell lineage and environmental factors. The differences in gene expression in these two types of muscle suggest that no single coordinated pattern of gene activation is required during the initial formation of the muscles of the mouse. PMID- 7787237 TI - Patterns of myosin isoforms in mammalian skeletal muscle fibres. AB - The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres. Four myosin heavy chain (MHC) isoforms, MHCI, MHCIIa, MHCIIb, and MHCIId(x), have been identified in small mammals and have been assigned to the histochemically defined fibre types I, IIA, IIB, and IID(X), respectively. These fibres express only one MHC isoform and are called pure fibre types. Hybrid fibres expressing two MHC isoforms are regarded as transitory between respective pure fibre types. The existence of pure and hybrid fibres even in normal muscles under steady state conditions creates a spectrum of fibre types. The multiplicity of fibre types is even greater when myosin light chains are taken into account. A large number of isomyosins results from the combinatorial patterns of various myosin light and heavy chains isoforms, further increasing the diversity of muscle fibres. As shown by comparative studies, the distribution of different fibre types varies in a muscle-specific, as well as a species-specific manner. PMID- 7787238 TI - Expression of myosin heavy chain isoforms and myogenesis of intrafusal fibres in rat muscle spindles. AB - This review concerns the pattern of expression and regulation of myosin heavy chain (MHC) isoforms in intrafusal fibres of rat muscle spindles detected by immunocytochemistry. The three types of intrafusal fibres--nuclear bag1, nuclear bag2, and nuclear chain fibres--are unique in co-expressing several MHCs including special isoforms such as slow tonic and alpha cardiac-like MHC and isoforms typical of muscle development, such as embryonic and neonatal MHC. The distinct intrafusal fibre types appear sequentially during rat hind limb development, the nuclear bag2 precursors being first identifiable at 17-18 days in utero as the only primary myotubes expressing slow tonic MHC. Sensory innervation is required for the expression of "spindle-specific" MHC isoforms. Motor innervation contributes to the diversity in distribution of the different MHCs along the length of the nuclear bag fibres. It is suggested that unique populations of myoblasts are destined to become intrafusal fibres during development in the rat hind limb muscles and that the regional heterogeneity in MHC expression is related both to sensory and motor innervation and to the properties of the myoblast lineages. These distinct features make intrafusal fibres an attractive in situ model for investigating myogenesis, myofibrillogenesis, and the mechanisms regulating MHC expression. PMID- 7787239 TI - Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates. AB - There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell. PMID- 7787236 TI - Development and postnatal regulation of adult myoblasts. AB - The myogenic precursor cells of postnatal and adult skeletal muscle are situated underneath the basement membrane of the myofibers. It is because of their unique positions that these precursor cells are often referred to as satellite cells. Such defined satellite cells can first be detected following the formation of a distinct basement membrane around the fiber, which takes place in late stages of embryogenesis. Like myoblasts found during development, satellite cells can proliferate, differentiate, and fuse into myofibers. However, in the normal, uninjured adult muscle, satellite cells are mitotically quiescent. In recent years several important questions concerning the biology of satellite cells have been asked. One aspect has been the relationship between satellite cells and myoblasts found in the developing muscle: are these myogenic populations identical or different? Another aspect has been the physiological cues that control the quiescent, proliferative, and differentiative states of these myogenic precursors: what are the growth regulators and how do they function? These issues are discussed, referring to previous work by others and further emphasizing our own studies on avian and rodent satellite cells. Collectively, the studies presented indicate that satellite cells represent a distinct myogenic population that becomes dominant in late stages of embryogenesis. Moreover, although satellite cells are already destined to be myogenic precursors, they do not express any of the four known myogenic regulatory genes unless their activation is induced in the animal or in culture. Furthermore, multiple growth factors are important regulators of satellite cell proliferation and differentiation. Our work on the role of one of these growth factors [platelet derived growth factor (PDGF)] during proliferation of adult myoblasts is further discussed with greater detail and the possibility that PDGF is involved in the transition from fetal to adult myoblasts in late embryogenesis is brought forward. PMID- 7787240 TI - Comparison of SEM processing methods for cultured human lens epithelial cells grown on flat and microcarrier bead substrates. AB - The increasing importance of in vitro models has presented new challenges in SEM processing techniques. The present study has evaluated the quality of preservation of cultured human lens epithelial cells processed by critical point, Peldri II, and tert-butyl alcohol drying. Specimens processed by critical point drying produced specimens with severe cracking of cell processes and microcracks across cell membrane surfaces. Peldri II and tert-butyl alcohol drying eliminated breakage of the filopodia and lamellipodia as well as eliminating the microcracks across the apical membrane surface. The morphology of lens epithelial cells grown on Cytodex 3 beads appeared rounded with convoluted membrane surfaces. These morphological features were present for cells processed by all three methods. Cytodex 3 beads were subsequently shown to shrink 52% in diameter during dehydration, which results in an 89% reduction in volume for the bead. Cells grown on Biosilon beads, which do not shrink, had a morphology similar to the cells grown on a flat substrate. These results indicate that Peldri II and tert butyl alcohol drying offer an attractive alternative to critical point drying when preparing cultured cells for SEM. Interpretation of cultured cell morphology must consider shrinkage of the substrate material as a possible contributor to artifact. PMID- 7787241 TI - Ultrastructural characterization of neurons recorded intracellularly in vivo and injected with lucifer yellow: advantages of immunogold-silver vs. immunoperoxidase labeling. AB - Immunoperoxidase labeling of lucifer yellow provides a sensitive method for morphological characterization of neurons recorded intracellularly in vitro or in vivo. However, the reaction product is often so dense that it obscures ultrastructural details necessary for the analysis of synaptic contacts onto individually filled neurons. In the present study, we describe a silver intensification procedure using 1 nm gold labeling of lucifer yellow as an optimal means for immunocytochemically identifying single physiologically characterized neurons at the ultrastructural level. Single neurons in the frontal cortex of anesthetized rats were impaled in vivo and filled with lucifer yellow. The brains were then perfused with an acrolein fixative. Single vibratome sections through the recording site were reacted with a rabbit antibody directed against lucifer yellow followed by goat anti-rabbit 1 nm gold-labeled IgG and silver intensified. For comparison, additional sections were processed for immunoperoxidase detection of lucifer yellow. Labeled sections were processed for light microscopy or embedded in plastic for electron microscopy. The immunogold silver label as well as peroxidase reaction product of lucifer yellow was readily detected in cell bodies, proximal and distal dendrites, and spines. However, in contrast to immunoperoxidase, the immunogold-silver reaction did not obscure subcellular organelles. Most importantly, the synaptic junctions formed by afferents to the filled neuron were more easily identifiable following the immunogold-silver procedure. This clear visualization of postsynaptic densities is essential for examining synaptic circuitry between afferents and physiologically characterized neurons. PMID- 7787242 TI - A fluorescent lipid analogue can be used to monitor secretory activity and for isolation of mammalian secretion mutants. AB - The use of reporter proteins to study the regulation of secretion has often been complicated by posttranslational processing events that influence the secretion of certain proteins, but are not part of the cellular mechanisms that specifically regulate secretion. This has been a particular limitation for the isolation of mammalian secretion mutants, which has typically been a slow process. To provide a reporter of secretory activity independent of protein processing events, cells were labeled with the fluorescent lipid analogue C5-DMB ceramide (ceramide coupled to the fluorophore boron dipyrromethene difluoride) and its secretion was followed by fluorescence microscopy and fluorescence activated cell sorting. Brefeldin A, which severely inhibits secretion in Chinese hamster ovary cells, blocked secretion of C5-DMB-ceramide. At high temperature, export of C5-DMB-ceramide was inhibited in HRP-1 cells, which have a conditional defect in secretion. Using C5-DMB-ceramide as a reporter of secretory activity, several different pulse-chase protocols were designed that selected mutant Chinese hamster ovary cells that were resistant to the drug brefeldin A and others that were defective in the transport of glycoproteins to the cell surface. Mutant cells of either type were identified in a mutagenized population at a frequency of 10(-6). Thus, the fluorescent lipid C5-DMB-ceramide can be used as a specific marker of secretory activity, providing an efficient, general approach for isolating mammalian cells with defects in the secretory pathway. PMID- 7787243 TI - Molecular cloning and characterization of human kinectin. AB - We have identified a human cDNA that is homologous to the chicken kinectin, a putative receptor for the organelle motor kinesin. The human cDNA clone hybridized to a single 4.6-kb mRNA species that codes for a protein of 156 kDa molecular mass. The predicted primary translation product contains an N-terminal transmembrane helix followed by a bipartite nuclear localization sequence and two further C-terminal leucine zipper motifs. In addition, the aminoacid sequence revealed a large region (327-1362) of predicted alpha-helical coiled coils. A monoclonal antibody CT-1 raised against a GST-kinectin fusion protein produced a perinuclear, endoplasmic reticulum-like staining pattern in diverse cell types from different species, indicating evolutionary conservation. Monoclonal antibody CT-1 and anti-chicken kinectin antibodies cross-reacted both in Western blotting and immunoprecipitation with a 160-kDa protein, confirming the antigenic identity of this 160-kDa protein with chicken kinectin. Epitope tagging studies revealed that the nuclear localization sequence motif of kinectin is not functional. Furthermore, a truncated kinesin cDNA lacking the N-terminal hydrophobic domain revealed a nonspecific cytoplasmic staining pattern. Together the data suggest that kinectin is an integral membrane protein anchored in the endoplasmic reticulum via a transmembrane domain. PMID- 7787244 TI - Characterization of kinectin, a kinesin-binding protein: primary sequence and N terminal topogenic signal analysis. AB - Kinectin is a kinesin-binding protein (Toyoshima et al., 1992) that is required for kinesin-based motility (Kumar et al., 1995). A kinectin cDNA clone containing a 4.7-kilobase insert was isolated from an embryonic chick brain cDNA library by immunoscreening with a panel of monoclonal antibodies. The cDNA contained an open reading frame of 1364 amino acids encoding a protein of 156 kDa. A bacterially expressed product of the full length cDNA bound purified kinesin. Transient expression in CV-1 cells gave an endoplasmic reticulum distribution that depended upon the N-terminal domain. Analysis of the predicted amino acid sequence indicated a highly hydrophobic near N-terminal stretch of 28 amino acids and a large portion (326-1248) of predicted alpha helical coiled coils. The 30-kDa fragment containing the N-terminal hydrophobic region was produced by cell-free in vitro translation and found to assemble with canine pancreas rough microsomes. Cleavage of the N terminus was not observed confirming its role as a potential transmembrane domain. Thus, the kinectin cDNA encodes a cytoplasmic-oriented integral membrane protein that binds kinesin and is likely to be a coiled-coil dimer. PMID- 7787245 TI - The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. AB - The ubiquitin-mediated degradation of mitotic cyclins is required for cells to exit from mitosis. Previous work with cell-free systems has revealed four components required for cyclin-ubiquitin ligation and proteolysis: a nonspecific ubiquitin-activating enzyme E1, a soluble fraction containing a ubiquitin carrier protein activity called E2-C, a crude particulate fraction containing a ubiquitin ligase (E3) activity that is activated during M-phase, and a constitutively active 26S proteasome that degrades ubiquitinated proteins. Here, we identify a novel approximately 1500-kDa complex, termed the cyclosome, which contains a cyclin-selective ubiquitin ligase activity, E3-C. E3-C is present but inactive during interphase; it can be activated in vitro by the addition of cdc2, enabling the transfer of ubiquitin from E2-C to cyclin. The kinetics of E3-C activation suggest the existence of one or more intermediates between cdc2 and E3-C. Cyclosome-associated E3-C acts on both cyclin A and B, and requires the presence of wild-type N-terminal destruction box motifs in each cyclin. Ubiquitinated cyclins are then rapidly recognized and degraded by the proteasome. These results identify the cyclosome-associated E3-C as the component of the cyclin destruction machinery whose activity is ultimately regulated by cdc2 and, as such, the element directly responsible for setting mitotic cyclin levels during early embryonic cell cycles. PMID- 7787246 TI - Control of the Cdc2/cyclin B complex in Xenopus egg extracts arrested at a G2/M checkpoint with DNA synthesis inhibitors. AB - Proliferating eukaryotic cells possess checkpoint mechanisms that block cell division in the presence of unreplicated or damaged DNA. Using cell-free extracts from Xenopus eggs, we have investigated the mechanisms underlying the inability of a recombinant Cdc2/cyclin B complex to induce mitosis in the presence of incompletely replicated DNA. We found that the activities of the kinases and phosphatases that regulate the major phosphorylation sites on Cdc2 (e.g., tyrosine 15, threonine 14, and threonine 161) are not altered significantly under conditions where Xenopus extracts remain stably arrested in interphase due to the presence of the replication inhibitor aphidicolin. However, at threshold concentrations, a Cdc2/cyclin B complex containing a mutant Cdc2 subunit that cannot be phosphorylated on either tyrosine 15 or threonine 14 displays a markedly reduced capacity to induce mitosis in the presence of aphidicolin. This observation indicates that the replication checkpoint in Xenopus egg extracts functions without the inhibitory tyrosine and threonine phosphorylation of Cdc2. We provide evidence that the checkpoint-dependent suppression of the Cdc2/cyclin B complex involves a titratable inhibitor that is regulated by the presence of unreplicated DNA. PMID- 7787249 TI - Annexin II marks astrocytic brain tumors of high histologic grade. AB - Annexin II is highly expressed in glioblastoma multiforme [Reeves, S. A.; Chavez Kappel, C.; Davis, R.; Rosenblum, M.; Israel, M. A. Developmental regulation of annexin II (lipocortin 2) in human brain and expression in high grade glioma. Cancer Res. 52:6871-6876; 1992] and is a likely second messenger in mitogenic pathways known to be important for the growth of these tumors. We have examined tumor tissue from patients diagnosed with low-, intermediate-, or high-grade astrocytic tumors for expression of annexin II by immunohistochemistry, and found that annexin II levels varied significantly among these three tumors (P < 0.0005). Levels were highest in glioblastoma multiforme, intermediate in anaplastic astrocytomas, and lowest in astrocytomas. In contrast to the usual cytoplasmic localization of annexin II, distinct nuclear staining was found in many of the specimens. Reactive astrocytes found in gliotic brain also stained with anti-annexin II antibody. We examined matched specimens for a correlation between annexin II staining intensity and the bromodeoxyuridine labeling index and found that, while tumors with the most intense annexin II staining had highest bromodeoxyuridine labeling indexes, there was not a strong association between these two parameters. The association between annexin II staining and histologic grade in astrocytic malignancies indicates that annexin II may be an important marker of high-grade glial tumors, and suggests that this marker may be useful for the pathologic classification of glial tumors and the clinical evaluation of brain tumor patients. PMID- 7787247 TI - Phosphorylation and activation of the Xenopus Cdc25 phosphatase in the absence of Cdc2 and Cdk2 kinase activity. AB - The M-phase inducer, Cdc25C, is a dual-specificity phosphatase that directly phosphorylates and activates the cyclin B/Cdc2 kinase complex, leading to initiation of mitosis. Cdc25 itself is activated at the G2/M transition by phosphorylation on serine and threonine residues. Previously, it was demonstrated that Cdc2 kinase is capable of phosphorylating and activating Cdc25, suggesting the existence of a positive feedback loop. In the present study, kinases other than Cdc2 that can phosphorylate and activate Cdc25 were investigated. Cdc25 was found to be phosphorylated and activated by cyclin A/Cdk2 and cyclin E/Cdk2 in vitro. However, in interphase Xenopus egg extracts with no detectable Cdc2 and Cdk2, treatment with the phosphatase inhibitor microcystin activated a distinct kinase that could phosphorylate and activate Cdc25. Microcystin also induced other mitotic phenomena such as chromosome condensation and nuclear envelope breakdown in extracts containing less than 5% of the mitotic level of Cdc2 kinase activity. These findings implicate a kinase other than Cdc2 and Cdk2 that may initially activate Cdc25 in vivo and suggest that this kinase may also phosphorylate M-phase substrates even in the absence of Cdc2 kinase. PMID- 7787248 TI - The bulk of unpolymerized actin in Xenopus egg extracts is ATP-bound. AB - Non-muscle cells contain 15-500 microM actin, a large fraction of which is unpolymerized. Thus, the concentration of unpolymerized actin is well above the critical concentration for polymerization in vitro (0.2 microM). This fraction of actin could be prevented from polymerization by being ADP bound (therefore less favored to polymerize) or by being ATP bound and sequestered by a protein such as thymosin beta 4, or both. We isolated the unpolymerized actin from Xenopus egg extracts using immobilized DNase 1 and assayed the bound nucleotide. High pressure liquid chromatography analysis showed that the bulk of soluble actin is ATP bound. Analysis of actin-bound nucleotide exchange rates suggested the existence of two pools of unpolymerized actin, one of which exchanges nucleotide relatively rapidly and another that apparently does not exchange. Native gel electrophoresis of Xenopus egg extracts demonstrated that most of the soluble actin exists in complexes with other proteins, one of which might be thymosin beta 4. These results are consistent with actin polymerization being controlled by the sequestration and release of ATP-bound actin, and argue against nucleotide exchange playing a major role in regulating actin polymerization. PMID- 7787250 TI - p53 mutations in bladder carcinoma cell lines. AB - Point mutations and deletions in the p53 tumor suppressor gene occur frequently in advanced stage bladder tumors. To extend these observations to an in vitro model of bladder tumorigenicity, we have evaluated the presence of p53 mutations in a panel of bladder carcinoma cell lines. p53 alleles were cloned using the reverse transcriptase-polymerase chain reaction method, and exons 2-11 were sequenced. Of 11 cell lines examined, 5 cell lines had missense point mutations, and each overexpressed p53 protein on western blot analysis. Except for the HT 1197 cell line, these point mutations occurred in evolutionarily conserved domains, which are characteristic hot spots for mutations. HT-1197 encodes an unusual C-terminal point mutation in codon 365, within the basic motif tetramerization domain, suggesting a linkage between induction of a mutant p53 conformation and alterations in protein oligomerization. Six of 11 cell lines had wild-type levels of p53 expression, with 4 producing p53 proteins having either internal deletions or truncations, and 2 producing wild-type p53. Presence of wild-type p53 was found only in cell lines derived from either a low-grade, papillary tumor (RT4) or fetal bladder (FHs 738Bl). The T24 cell line was found to contain a novel p53 mutant having an in-frame deletion of tyrosine 126. This p53 mutant does not bind SV40 large T antigen, yet is expressed at low levels, comparable to cell lines containing wild-type p53 alleles. Our findings characterize p53 mutations in a panel of bladder carcinoma cell lines, and provide a model for testing the role of wild-type or mutant p53 cDNA to suppress or induce tumorigenic properties. PMID- 7787251 TI - Enhanced cytotoxicity with interleukin-1 alpha and 5-fluorouracil in HCT116 colon cancer cells. AB - Recombinant human interleukin-1 alpha (rIL-1 alpha), at concentrations that were not growth-inhibitory when given alone (100-10,000 U/ml), enhanced the growth inhibition resulting from a 72-h fluorouracil (FUra) exposure in HCT116 colon cancer cells. Median-effect analysis of clonogenic assays indicated that rIL-1 alpha, given 24 h prior to and following a 24-h exposure to FUra, increased lethality in a more than additive fashion. rIL-1 alpha did not appear to significantly affect [3H]-FUra metabolism, total [3H]-FUra-RNA incorporation or RNA retention after drug removal, inhibition of thymidylate synthase, or thymidine triphosphate pool depletion. During continuous exposure to rIL-1 alpha, transient stimulation of RNA and DNA synthesis was observed at 72 h, with a return to normal by 96 h. A 24-h exposure to 10 microM FUra altered the elution profile of newly synthesized DNA as monitored by pH step alkaline elution. An accumulation of lower-MW single-stranded DNA species was noted with FUra compared to control, accompanied by a significantly decreased proportion of DNA retained on the polycarbonate filter: 10% retained vs. 32% for control (P = 0.01). A 48-h exposure to rIL-1 alpha alone did not affect the elution profile of nascent DNA species, nor did it enhance the effects of FUra. Although FUra did not appreciably affect pulse [3H]-uridine incorporation into RNA for the initial 8-24 h of FUra exposure, progressive inhibition of net RNA synthesis was observed thereafter. FUra prevented the stimulatory effect of rIL-1 alpha on RNA synthesis, and net RNA synthesis was significantly inhibited (by 64-79% after 72 and 96 h) with the combination compared to rIL-1 alpha alone. Continuous exposure to 10 microM thymidine did not rescue cells from the lethality of FUra alone or the combination of FUra plus rIL-1 alpha, suggesting that depletion of deoxythymidine triphosphate as a consequence of thymidylate synthase inhibition was not the most important component of FUra toxicity. In contrast, 1 mM uridine provided partial protection against the toxicity of FUra alone or with rIL-1 alpha. Although uridine did not affect FUra metabolism, it decreased FUra-RNA incorporation by 42-60%, presumably as a consequence of the 2-fold expansion of UTP pools. [125I]-rIL-1 alpha binding was nonspecific; with a 24-h exposure, however, internalized [125I]-rIL-1 alpha exceeded cell surface-bound material by 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787253 TI - Whole-body autoradiographic study of [3H]-PK 11195 distribution in dunning AT-1 tumour-bearing rats. AB - In vivo binding of [3H]-PK 11195 to peripheral benzodiazepine binding sites in Dunning AT-1 prostatic tumour-bearing rats was investigated by whole-body autoradiography. Distribution and retention of PK 11195 in tumour and other organs was examined at different time intervals. Autoradiograms indicated PK 11195 binding sites in the periphery of the tumour, whereas no or little binding was detected in the prostate. Among other organs, adrenal cortex was most intensely radiolabelled. Administration of nonradioactive PK 11195 before [3H]-PK 11195 blocked binding in all organs more completely than in tumour, kidney, and adrenal cortex, where low levels of radioactivity still were present. Radioactivity in the tumour, contrary to other organs, seemed to increase with time, indicating a slow uptake with large capacity. High performance liquid chromatography analysis of extracted radioactivity from the tumour showed that almost all radioactivity consisted of intact [3H]-PK 11195. These results indicate binding in vivo of PK 11195 to peripheral benzodiazepine receptors in Dunning AT-1 rat prostatic tumours and a large capacity for uptake and retention of [3H]-PK 11195 in tumours. PMID- 7787252 TI - Effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells. AB - The effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Even at low concentrations, bupivacaine decreased the oxygen uptake rate, but its effect was remarkably higher on the uncoupled respiration. Experiments on specific segments of the respiratory chain have shown that bupivacaine did not inhibit electron transport from Q to oxygen. Spectroscopic evidences demonstrated a NAD(P)H oxidation in bupivacaine-treated cells respiring on endogenous substrates, indicating that the inhibition of oxygen depended on a reduced electron transport from site 1 entering substrates to respiratory chain. The aerobic glycolysis was stimulated by low and inhibited by high bupivacaine concentrations. The increased lactate production rate was due to an activation of mitochondrial ATPase, whereas its decrease was related to an inhibition of the hexokinase activity. PMID- 7787256 TI - Arrhythmias. PMID- 7787254 TI - Biological activity of human N-ras and K-ras genes containing the Asn17 dominant negative mutation. AB - Substitution of asparagine for serine at position 17 of human H-ras results in an impaired GTP-binding activity, causing the mutant Ras protein to be locked in a constitutively inactive GDP-bound state. Expression of this mutant in NIH 3T3 cells inhibits cell proliferation by blocking endogenous ras function. Plasmids that encode the analogous dominant negative mutation at position 17 in human N- and K-ras were constructed. These mutant ras genes, driven by a heavy metal inducible sheep metallothionein promoter, were introduced by transfection into a variety of animal cell lines. All three mutant ras genes displayed an inhibitory phenotype when expressed in NIH 3T3 cells. This inhibition could be overcome by cotransfection with either activated H-ras or v-raf. These data indicate that the three human Ras proteins probably act through the same signal transduction pathway in NIH 3T3 cells and suggest that these mutations may confer similar phenotypes to other GTP/GDP-binding proteins. PMID- 7787255 TI - Reference listings in cancer research. PMID- 7787257 TI - Pediatrics. PMID- 7787258 TI - Arrhythmogenic right ventricular dysplasia. AB - Arrhythmogenic right ventricular dysplasia is a relatively newly described clinical entity that is more and more frequently recognized. It may explain an increasing number of unexpected, sudden deaths in young adults that are or are not preceded by cardiac symptoms. A genetic transmission of the disease has been suggested by the study of familial cases. A location on chromosome 14 appears to be responsible for this disease. In some patients, a superimposed inflammatory process mixed with the pattern of arrhythmogenic right ventricular dysplasia may explain the progressive deterioration of left ventricular function. The systematic study of electrocardiograms demonstrates prolongation of the QRS complex and repolarization abnormalities in the right precordial leads due to a parietal block. Multiple therapeutic approaches are now available. The first line of therapy remains antiarrhythmic drugs, which are effective in most cases. Ablative techniques, implantable defibrillators, and heart transplantation have been used in the most severe examples of the disease. PMID- 7787259 TI - Catheter ablation of ventricular tachycardia. AB - Endocardial lesions created by radiofrequency catheter ablation are relatively small and focal. The application of radiofrequency ablation to patients with structural heart disease and ventricular tachycardia is quite limited because the substrate for these tachycardias is often diffuse or difficult to localize. In contrast, idiopathic ventricular tachycardia often originates from a discrete focus and can usually be ablated using radiofrequency energy. The wider applicability of ablation therapy for ventricular tachycardia will depend on improvements in mapping techniques and the ability to create larger areas of injury in patients with coronary artery disease and ventricular tachycardia. PMID- 7787260 TI - Antiarrhythmic drug interactions. PMID- 7787261 TI - Health care reform and belt tightening: how can we become more cost effective? Commentary. PMID- 7787262 TI - New insights on anatomical location of components of the reentrant circuit and ablation therapy for atrioventricular junctional reentrant tachycardia. AB - The success of radiofrequency catheter ablation in the treatment of atrioventricular junctional, or atrioventricular nodal, reentrant tachycardia has rekindled interest in the electrophysiological and anatomical characteristics of the reentrant circuit. We conclude that there is no evidence that within the atrioventricular nodal area, which contains both the compact node and transitional cells, there are anatomically delineated dual or multiple pathways. Rather, the two main atrial inputs into the atrioventricular nodal area (posterior and anterior) seem to be the anatomically relevant structures for "slow" and "fast" pathways. Two other inputs (sinus septum and left atrial) may be the cause for multiple pathways in some individuals. Nonuniform anisotropic properties of the zone of transitional cells may account for slow or fast conduction in the same area, depending on directional differences of wavefronts. We prefer the term atrioventricular junctional reentrant tachycardia rather than atrioventricular nodal reentrant tachycardia because of mounting evidence that perinodal tissue is involved in the reentrant circuit. Finally, the role and origin of double extracellular electrograms is discussed. Further research is required to establish whether an anatomical or an electrogram-guided approach for catheter ablation is preferred. PMID- 7787263 TI - The molecular genetics of cardiovascular disease. AB - The following consideration of this past year's published studies uses the cited reports as important examples of the ongoing characterization of the molecular basis of cardiac disease and the process of cardiac development. Mutations in cardiac troponin T and alpha-tropomyosin have been identified in familial hypertrophic cardiomyopathy, as have new beta-myosin heavy chain gene mutations. The general relation between beta-myosin heavy chain gene mutations that produce a charge change versus conservative amino acid replacements and sudden death remains unresolved. New fibrillin 1 gene mutations have been identified in patients with Marfan syndrome, the neonatal form of Marfan syndrome, and ectopia lentis. The same mutation is rarely found in more than one family. The association of supravalvar aortic stenosis and elastin gene mutations was further strengthened. The complexity of the relation between dystrophin mutations and the cell-specific loss of dystrophin expression can result in patients having cardiomyopathy and no myopathy. X-chromosome inactivation was shown to be the basis of cardiomyopathy in women with a single mutated dystrophin allele. New candidate genes that control cardiac morphogenesis and myocyte differentiation were proposed. New evidence to support 22q11 microdeletions as a common basis of nonsyndromic conotruncal malformations was published. These studies represent an important beginning. Although mutant genes have been recognized in affected individuals with various syndromes and congenital cardiac abnormalities, our understanding of how a genotype yields a given phenotype remains to be established. PMID- 7787264 TI - Recent insights into the regulation of cardiac Ca2+ flux during perinatal development and in cardiac failure. AB - Systolic and diastolic cardiac function improve during the transition from fetus to newborn to adult. This perinatal maturation is temporally correlated with and at least partially dependent on subcellular changes in the expression of several gene products that regulate cytosolic Ca2+ concentration. Expression of the Na(+) Ca2+ exchanger of the sarcolemma is highest in the fetus, whereas expression of the sarcoplasmic reticulum Ca2+ pump and the voltage-dependent Ca2+ channel of the sarcolemma increase in conjunction with the perinatal maturation of cardiac function. Whereas cardiac relaxation in the normal mature heart depends primarily on the sarcoplasmic reticulum Ca2+ pump, relaxation in the fetal heart appears to be more dependent on transsarcolemmal Ca2+ flux. Like the fetal heart during prolonged relaxation, the failing human heart exhibits impaired relaxation and abnormal Ca2+ flux regulation. Although altered expression of several gene products has been demonstrated in the failing heart, the responsible factor(s) remains unknown. PMID- 7787266 TI - Congenital cardiovascular disease and cardiac surgery in childhood: Part 1. Cyanotic congenital heart defects. AB - The management of congenital heart disease is in a state of evolution, with earlier surgical and/or catheter interventions dominating clinical decision making. Recent advances in interventional cardiac catheterization techniques, as well as continuing advances in the surgical management of complex congenital defects, continue to be the focus of attention of cardiologists and surgeons. The majority of the papers reviewed document mid- and long-term results of specific operative procedures for and address the appropriate role of cardiac catheterization techniques in the management of transposition of the great vessels, tetralogy of Fallot, total anomalous pulmonary venous connection, truncus arteriosus, pulmonary atresia with intact ventricular septum, and the univentricular heart. Early definitive intervention has become the standard of care for almost all defects reviewed. PMID- 7787265 TI - Fetal arrhythmias, pediatric arrhythmias, and pediatric electrophysiology. AB - The practice of pediatric electrophysiology has been altered drastically and irrevocably over the past 5 years. With the advent of widespread application of transcatheter radiofrequency ablative techniques in young patients, decision making in the management of childhood arrhythmias has focused less on palliative medical therapies and more on the potential for curative, nonsurgical interventions. This review examines the published contributions in the area of pediatric catheter ablation, antiarrhythmic drug therapy, postoperative arrhythmias, fetal arrhythmias, and electrocardiographic phenomena after cardiac transplantation. PMID- 7787267 TI - Congenital cardiovascular disease and cardiac surgery in childhood: Part 2. Acyanotic congenital heart defects and interventional techniques. AB - The literature for the period reviewed documents a significant reduction of morbidity and mortality for neonatal repairs of atrioventricular septal defects, coarctation of the aorta, and ventricular septal defects. Long-term follow-up of patients with coarctation of the aorta provides important suggesting that earlier repair of asymptomatic coarctation and complete elimination of obstruction in the arch as well as at the coarctation site are essential to better long-term results. Surgery for complete atrioventricular septal defect has evolved from palliation, with poor long-term results, to complete repair within the first 6 months of life, with minimal morbidity and mortality. Special emphasis is now placed on children with Down's syndrome who have complete atrioventricular septal defects; data confirm their tendency for earlier development of pulmonary vascular obstructive changes. Further refinements in surgical and interventional catheterization techniques have resulted in promising advances for many lesions- coarctation of the aorta (native and recurrent); valvular, subvalvular, and supravalvular aortic stenosis; valvular pulmonary stenosis; patent ductus arteriosus; and branch pulmonary artery stenosis--and have prompted provocative discourse between cardiologists and surgeons. These refinements in surgical and interventional techniques have initiated a new era in the clinical management of congenital heart disease in childhood. PMID- 7787268 TI - Advances in acquired pediatric heart disease. AB - Acquired heart disease in children may result in significant morbidity and mortality. Advances continue to be made in understanding Kawasaki disease, acute and chronic rheumatic heart disease, infective endocarditis, myocarditis, and dilated cardiomyopathy. The role of superantigens, particularly bacterial toxins, in the pathogenesis of Kawasaki disease continues to be defined. Intravascular ultrasound promises to improve the assessment of coronary arteries in Kawasaki disease. Current recommendations for the long-term management of Kawasaki disease are discussed. Significant changes in the epidemiology of acute rheumatic fever and endocarditis are noted. Updates on the role of echocardiography as well as current therapeutic issues in these diseases are addressed. The application of immunologic and molecular biologic techniques have implicated genetic and immune factors in the pathogenesis of myocarditis and cardiomyopathy. The relationship between viral infection and subsequent dilated cardiomyopathy, as well as the role of autoimmune mechanisms in the pathogenesis of these disorders, remains controversial. PMID- 7787269 TI - New perspectives in childhood blood pressure. AB - Ambulatory blood pressure monitoring is a new technique available to the pediatric cardiologist, and several studies have investigated its usefulness. Investigators are now providing data for both normal values and reproducibility. Other authors have examined the effects of hypertension in mothers upon their offspring, which include small birthweight and possible developmental delay. New data, particularly from the Bergen Blood Pressure Study, indicate that maternal hypertension may be a precursor for future blood pressure elevation in offspring. It is known that obese people are more likely to be hypertensive. A study performed in China in a lean population, including individuals who were relatively obese, showed the positive relation of body weight to blood pressure. Furthermore, data now emerging indicate that both retinal vessels and renal arteries in children suffer changes with persistently elevated blood pressure. This clearly is something to follow. Other articles examined in this review investigate the relation of atherosclerosis to hypertensive disease. PMID- 7787270 TI - Identification of patients with hypertrophic cardiomyopathy at high risk for sudden death. AB - Patients with hypertrophic cardiomyopathy are at increased risk for sudden death. Recent studies have improved our ability to risk-stratify such patients and have elucidated several potential mechanisms of sudden death and syncope. Certain noninvasive tests, such as signal-averaged electrocardiography and measurements of cardiac autonomic function and QT/QT dispersion, are often abnormal in hypertrophic cardiomyopathy, but are not useful for risk stratification. Myocardial ischemia determined by exercise thallium scintigraphy, however, identifies young patients with hypertrophic cardiomyopathy who are at high risk for cardiac arrest and syncope. Nonsustained ventricular tachycardia on ambulatory Holter monitoring in the absence of symptoms of impaired consciousness is associated with a benign prognosis and is not predictive of sudden death. Conversely, ventricular tachycardia induced at electrophysiologic study identifies adult patients with hypertrophic cardiomyopathy who subsequently experience sudden death. Finally, characterization of the natural history of the genetic defects will increasingly become an integral part of risk evaluation in hypertrophic cardiomyopathy. PMID- 7787271 TI - Adult congenital heart disease. AB - Much of the literature published in 1993 on the topic of adult congenital heart disease described long-term follow-up of patients following repair in childhood. This report reviews the most important papers published during the past year related to long-term follow-up, and also describes new information on the noninvasive evaluation of congenital heart disease in adults as well as the interventional cardiologic techniques that are currently being applied to treat some defects in the catheterization laboratory. PMID- 7787272 TI - Valvular heart disease. PMID- 7787273 TI - Heart transplantation. PMID- 7787274 TI - Advances in noninvasive assessment of valvular heart disease. AB - Echocardiography continues to be the noninvasive method of choice in the evaluation of valvular heart disease. Important recent developments include clinical validation of approaches used to quantify valvular regurgitation, in particular the proximal flow convergence zone method; use of transesophageal imaging to monitor and evaluate surgical or percutaneous interventions in valvular heart disease, in particular mitral valve repair; insight into flow related stretch of the orifice area in aortic stenosis; and validation of nuclear magnetic resonance imaging in small series for quantification of left-sided valvular stenotic and regurgitant lesions. PMID- 7787275 TI - Recent developments in the diagnosis and management of mitral valve prolapse. AB - Mitral valve prolapse (MVP), which occurs in about 3% of adults, is usually a primary, dominantly inherited condition. MVP may be diagnosed by auscultation of a mid-systolic click and late-systolic murmur that move dynamically with postural maneuvers. M-mode echocardiography confirms MVP by demonstrating late-systolic prolapse and two-dimensional echocardiography reveals leaflet billowing into the left atrium. Echocardiography identifies severe forms of MVP by documenting significant mitral regurgitation, enlargement and thickening of the mitral leaflets and annulus, and loss of leaflet apposition. In contrast to early reports, true "MVP syndrome" as revealed by controlled studies consists of low body weight and blood pressure, minor skeletal abnormalities, orthostatic hypotension, palpitations, and mitral regurgitation that is usually mild. Complications of MVP include progressive mitral regurgitation, infective endocarditis, orthostatic syncope, and possible risks of neurologic ischemia and arrhythmic sudden death. Risk factors we have identified for complications among patients with MVP include older age, male gender, the presence of mitral regurgitation, and possibly, higher weight and blood pressure. The cumulative risk of all complications of MVP by age 75 is from 5% to 10% for affected men and 2% to 5% for affected women. Patients with MVP who have neither a murmur nor Doppler evidence of mitral regurgitation may be reassured that their condition is benign. For other patients with MVP we have shown that oral antibiotic prophylaxis is cost-effective. The presence and severity of mitral regurgitation govern the frequency and intensiveness of follow-up. PMID- 7787276 TI - Management of valvular stenosis. AB - The management of valvular stenosis has changed dramatically over the past 15 years, largely due to interventional cardiology. At the beginning of the 1980s, balloon valvuloplasty was thought by many to represent a definitive new treatment for calcific aortic stenosis in the elderly infirm. Before the end of the decade, this treatment had gone out of favor, but by that time we had learned that many of those same patients could undergo aortic valve replacement relatively safely and with excellent results. Unlike aortic stenosis, mitral stenosis is a disabling rather than a lethal disease, so the timing of intervention is much more difficult, particularly as there are treatment choices. Mortality, morbidity, and the possible bonus from proceeding earlier rather than later all need to be taken into consideration. Much to many people's surprise, mitral balloon valvuloplasty has grown and prospered, especially since the introduction of the Inoue balloon. It is the treatment of choice for young patients with mobile, noncalcified, stenosed valves, although still offering worthwhile palliation for older patients with higher echocardiographically determined valve scores. Echocardiography has gradually usurped cardiac catheterization for the assessment of valve stenosis and left ventricular function, but in patients with concomitant coronary disease that will be treated at the same time, the need for coronary angiography remains almost unchallenged. PMID- 7787277 TI - Management of valvular regurgitation. AB - The principles of the management of left-sided valvular regurgitation, which weigh watchful waiting against surgery, have crystallized over the past 15 years. While the timing of surgery once was enigmatic, it is now clear that surgery must be done prior to the development of prolonged left ventricular dysfunction. Fortunately, satisfactory indexes have been developed that allow the clinician to detect and avoid such dysfunction. Therefore, patients now undergo surgery sooner, resulting in reduced operative mortality and better long-term survival. However, there are still several unresolved issues regarding the management of valvular regurgitation. For instance, operations for mitral regurgitation that preserve the mitral apparatus improve postoperative left ventricular performance compared with conventional mitral valve replacement. However, the proper timing for these operations is still being examined. Another issue is whether vasodilators, which reduce the regurgitant overload, can delay the onset of ventricular dysfunction and thus also delay surgery. In contemplating vasodilator use there is a paradox between the principle of early surgery to prevent dysfunction and use of medical therapy to delay surgery. Several studies which have appeared in the literature in the past year help resolve some of these issues. PMID- 7787278 TI - Recent developments in balloon valvuloplasty techniques. AB - The long-term outcome after mitral valvuloplasty is excellent and compares well with surgical treatment of mitral stenosis. Compared with the double balloon technique, the Inoue method is technically easier and may reduce acute complications without any adverse effect on long-term outcomes. Excellent long term outcome is also seen after balloon valvuloplasty of aortic stenosis in the young and in pulmonary stenosis at all ages. Finally, although balloon aortic valvuloplasty in the elderly may not change the terrible prognosis of such patients, it does improve functional status and is a useful bridge to surgery in selected patients. PMID- 7787279 TI - Surgical repair and reconstruction of valvular lesions. AB - Thirty-six years have passed since the inception of mitral valve repair by Lillehei and McGoon. In the period presently under review it is apparent that mitral valve repair and the late results have become more predictable. Previously, repair was not attempted because of concern that valve replacement, with its attendant problems, might be necessary. This attitude appears to be slowly changing. The current issue is whether patients who have severe mitral regurgitation but are relatively asymptomatic should be referred for repair before ventricular function deteriorates or atrial fibrillation develops. Current evidence suggests that approximately 10% of asymptomatic patients will progress sufficiently each year to require surgical intervention. Systolic anterior motion of the mitral valve causing left ventricular outflow tract obstruction, has, since the era of routine intraoperative transesophageal echocardiography, become a well-recognized occasional consequence of mitral valve repair. Numerous theories have been suggested as to its cause: the most plausible suggest that risk factors include the presence of excess valvular tissue, a bulging septum, a nondilated hyperdynamic left ventricle, and a narrow mitral-aortic angle. The fact that numerous annuloplasty techniques exist, each having its own proponent(s), suggests that different techniques or types of annuloplasty are equally effective. Reparative techniques for the aortic valve have lagged behind those for the mitral valve because of limited previous success. The type of valve pathology was recently classified in terms of repair and new techniques, which are briefly documented, have been tried.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787280 TI - Which prosthetic valve should we choose? AB - In this review I concentrate on issues related to prosthetic valves themselves: their development, performance, and durability. For example, mechanical failure or tissue deterioration appear to be intrinsic properties of the valve and are therefore central to my topic, whereas the development, diagnosis, and management of endocarditis are largely independent of the type of prosthesis and are thus not dealt with here. Other outcomes such as stroke are also determined by factors other than the choice of valve, as was cogently argued in papers published during the past year. The papers on tissue valves have a common theme: they document the inevitability of tissue failure, too early for acceptable use other than in old age. The mechanical valves that have stood the test of time have done so because they do not fail. PMID- 7787282 TI - Heart transplantation. PMID- 7787281 TI - New developments in infective endocarditis. AB - Endocarditis as seen today differs significantly from that outlined by Sir William Osler in his famous Gulstonian lectures in 1885. The median age of the patients has increased; the spectrum of predisposing cardiac lesions has changed; more cases are due to unusual organisms, including gram-negative bacteria and fungi; and more cases present acutely and the classic findings of late endocarditis are seldom seen. Endocarditis was untreatable and uniformly fatal in 1885. Although continued advances in medical and surgical therapy have significantly increased survival, the recent appearance of multiresistant organisms in some cases is reminiscent of the Osler era. Recent advances in the diagnosis and management of endocarditis include the identification of a specific Staphylococcus aureus receptor protein on endothelial cells, better imaging of the cardiac structures using transesophageal echocardiography, improvement in clinical diagnostic criteria and surgical techniques, and the use of outpatient oral antibiotics for penicillin-sensitive streptococcal endocarditis. PMID- 7787283 TI - Candidate evaluation and selection for heart transplantation. AB - Because of the increasing discrepancy between the number of identified candidates for heart transplantation and available donor organs, appropriate selection of patients for heart transplantation is critical. The establishment of a cardiac prognosis that is significantly worse than that following heart transplant is central in the determination of candidacy for transplantation. However, with recent improvements in heart failure management, prognosis must be considered a dynamic state involving periodic reassessment to ensure an individual's ongoing suitability for transplantation. There have been many descriptions of prognostic indexes in heart failure, but care must be used when extrapolating observations collected from patients with a broad range of conditions to those with end-stage disease. The contraindications to heart transplantation have also evolved with the increasing success of the transplant process. Many conditions that precluded patients from heart transplant in the past are no longer regarded as absolute. Despite less stringent conditions for recipient candidacy, the need to achieve optimal results with an increasingly valuable donor resource will necessitate careful scrutiny of the posttransplant implications of the various conditions currently regarded as contraindications to heart transplant. Determination of heart transplantation candidacy therefore continues to remain a highly individualized process, requiring clinical judgment and experience. PMID- 7787284 TI - Socioeconomic aspects of heart transplantation. AB - Heart transplantation is an established treatment modality for end-stage cardiac disease. Unfortunately, relative to other health care priorities, heart transplantation has fallen into disrepute. Efforts to reform the health care system have focused on three fundamental issues--cost, quality, and access. On each count, heart transplantation is vulnerable to criticism. Managed care is an incremental approach to health care reform that imposes fiscal constraint on providers. This constraint is expressed in the form of capitation which, in turn, requires providers to assume risk and accept economic responsibility for clinical decisions. While the need for transplantation is considerable, there are both clinical and economic factors limiting the overall level of activity. In 1993, over 2200 heart transplants were performed in the United States on people who were dying of end-stage cardiac disease. The total demand for heart transplantation was estimated to be about 5900 persons, which was not met due to an insufficient supply of donor hearts. Absent donors, the fiscal consequences of heart transplantation are minimized. In 1993, actuaries estimated that the total charge per heart transplant was $209,100. By designating centers based on price and quality considerations, managed care plans have reduced this per procedure expense to less than $100,000. While the benefits of transplantation are noteworthy, there are still concerns. Sixty percent of patients report that they are able to work, but only 30% do so. Employers hope to improve upon this record by expanding the designated center approach. In conclusion, the future of heart transplantation is unclear. Opportunities for innovation are limited, although the management of heart failure is an area of increased interest. PMID- 7787285 TI - Clinical follow-up of the heart transplant recipient. AB - Long-term survival of heart transplant recipients is now commonplace, due to improved perioperative care. It is thus appropriate to review recent studies concerning immunosuppression-related clinical problems in heart transplant recipients, including infections, malignancies, hypertension, hyperlipidemia, and osteoporosis. Hormonal and peripheral vascular responses of the denervated heart, exercise tolerance, pulmonary function, and parenting are also discussed. PMID- 7787286 TI - Immunopathology of cardiac transplant rejection. AB - Transplant rejection represents a diverse series of complex immunological events beginning with allorecognition and lymphocyte activation and differentiation, followed by interactions of antibodies and activated lymphocytes with the vascular endothelium and subsequent cellular infiltration into the allograft, and, finally, the inflammatory process leading to tissue injury. This paper reviews how these events contribute to the different types of cardiac transplant rejection, including cardiac allograft vasculopathy. PMID- 7787287 TI - Immunosuppression in cardiac transplantation: a new era in immunopharmacology. AB - During the past 5 years, there has been a concerted effort to identify new immunosuppressive agents for organ transplantation that have greater efficacy and fewer side effects than current therapies (corticosteroids, azathioprine, cyclosporine, anti-T cell antibodies). These new drugs can be generally classified according to their varying structures or mechanisms of action: xenobiotic molecules (FK506, rapamycin, cyclosporine analogues); antimetabolites (mycophenolate mofetil, mizoribine, brequinar sodium); and those agents with novel or incompletely defined mechanisms of action (leflunomide, 15 deoxyspergualin). Many of the newer agents offer better therapeutic indexes, and some even show promise in the treatment of two of the major obstacles currently facing cardiac allograft transplantation: antibody-mediated accelerated humoral rejection and chronic vascular rejection (also known as accelerated graft coronary artery disease). With the increasing shortage of donor organs in recent years, there has been a resurgence of interest in xenotransplantation; some of the new immunosuppressants demonstrate efficacy in prolonging xenograft survival. Most of these agents will probably find their niches as components of low-dose combination regimens designed to maximize effective immunosuppression and minimize drug toxicities and opportunistic infections. PMID- 7787288 TI - Alternatives to human heart replacement. AB - The continuing and increasing discrepancy between the number of available donor hearts and the number of patients who might benefit from cardiac transplantation has prompted efforts in the development of xenotransplantation, mechanical assist devices, and cardiomyoplasty techniques. We briefly review recent work in these three fields. The results of experimental xenotransplantation between closely related species are improving slowly with currently available drugs, and clinical trials in this field may be possible in the near future. Implantable ventricular assist devices are also at a stage of development where permanent implantation is likely to be followed by a reasonable and worthwhile period of patient survival. With regard to cardiomyoplasty, steady progress is being made in clarifying exact indications and patient selection, as well as confirming the potential benefits. PMID- 7787290 TI - Therapeutic interventions in valvular heart disease: lessons about timing learned over time. PMID- 7787289 TI - Pediatric heart transplantation. AB - Studies from a number of centers have documented the growth and success of pediatric heart transplantation. The 1st year of life is the period of greatest mortality from congenital heart disease and has now become the single most frequent age of pediatric heart transplantation. Appropriately, congenital heart disease is the most common diagnosis leading to heart transplantation. Early mortality is still greatest in recipients who undergo transplantation during the 1st year of life. The patients at greatest risk are being identified and new maneuvers to lower early mortality are emerging. Long-term follow-up continues to indicate excellent late survival with low morbidity. This review focuses on key advances in knowledge reported in the last year. PMID- 7787291 TI - Systemic release of mucosal mast-cell protease in primed brown Norway rats after feeding with beta-lactoglobulin. AB - The plasma level of mucosal mast-cell protease was examined to find whether such measurements could be an indicator of allergic response to beta-lactoglobulin (beta-LG) challenged orally by rats. Brown Norway rats, which had been raised on a bovine milk-free diet, were systemically sensitized on day 0 with a low dose of beta-LG, and then by an oral administration of beta-LG for 3 h on day 14. The oral challenge with beta-LG in saline, when compared to saline alone, resulted in a systemic elevation of rat mast-cell protease II (RMCPII), one of the specific markers for gut mucosal mast-cell secretion. The challenge with beta-LG in a fat emulsion further increased the level of plasma RMCPII. This manipulation, however, was not successful for detecting any significant difference in mucosal leucotriene C4, another allergic mediator. An oral challenge with polymerized beta-LG did not induce any elevation of the protease, but resulted in a lower plasma level of beta-LG-specific IgG. This animal model is thus relevant to investigate the events regulating the mucosal hypersensitivity and humoral immunity to food proteins. PMID- 7787293 TI - Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. AB - We investigated the mechanism for the inhibition of fat digestion by chitosan, and the synergistic effect of ascorbate. The important inhibition characteristics of fat digestion by chitosan from observations of the ileal contents were that it dissolved in the stomach and then changed to a gelled form, entrapping fat in the intestine. The synergistic effect of ascorbate (AsA) on the inhibition of fat digestion by chitosan is thought not to be acid-dependent but due to the specificity of AsA itself, according to the data resulting from using preparations supplemented with sodium ascorbate (AsN). The mechanism for the synergistic effect is considered to be 1) viscosity reduction in the stomach, which implies that chitosan mixed with a lipid is better than chitosan alone, 2) an increase in the oil-holding capacity of the chitosan gel, and 3) the chitosan fat gel being more flexible and less likely to leak entrapped fat in the intestinal tract. PMID- 7787292 TI - Effect of the viscosity or deacetylation degree of chitosan on fecal fat excreted from rats fed on a high-fat diet. AB - Several chitosan preparations, either with a comparable degree of deacetylation but differing viscosity or with comparable viscosity but a differing degree of deacetylation, were examined for their effect on the fecal fat excreted from rats fed on a high-fat diet. As the viscosity or deacetylation degree of a chitosan preparation increased, the more its effect on the apparent fat digestibility by rats became conspicuous. A supplement of ascorbic acid to each chitosan diets resulted in a significant depression of fat digestion and absorption in the lumen. The chitosan intake caused a higher level of fat to be excreted in the feces of the corn oil-receiving rats than the lard-receiving ones, although the effect was strong with both diet groups. PMID- 7787294 TI - Change in the distribution of alpha-tocopherol stereoisomers in rats after intravenous administration. AB - Synthetic alpha-tocopherol (alpha-Toc) contains equal amounts of eight different stereoisomers arising from three chiral centers in the phytyl tail. Of these, the four stereoisomers with the 2R configuration are generally more active than their corresponding 2S-isomers. We investigated the change in distribution of alpha-Toc stereoisomers in the plasma and tissues after intravenously administering all-rac and SRR-alpha-Toc acetate. The concentration of 2R-isomers in the rat plasma after administering all-roc-alpha-Toc acetate was higher than that of the 2S isomers. On the other hand, the concentration of 2R-isomers in the liver was lower than that of 2S-isomers up to 6 h. In the rat plasma after administering only SRR-alpha-Toc acetate, no SRR-alpha-Toc was detected after 6 h, although SRR alpha-Toc in the liver was retained at a higher level than in the other tissues. We presume that the intravenously administered 2R- and 2S-isomers were easily transported into the liver from the plasma, the 2R-isomers being preferentially released from the liver into the blood, whereas the 2S-isomers remained in the liver for up to 6 h. PMID- 7787296 TI - Measurement of superoxide dismutase-like activity of natural antioxidants. AB - The superoxide dismutase (SOD)-like activity of natural antioxidants was evaluated by measuring the inhibition of pyrogallol autoxidation that is catalyzed by the superoxide radical. Among 22 water-soluble antioxidants tested, L-ascrobic acid, L-ascorbic acid 6-palmitate, glutathione (reduced form), (+) catechin, and (-)-epicatechin showed effective SOD-like activity. To analyze lipophilic antioxidants, an optically clear organic system composed of diethyl ether, surfactant (dioctyl sulfosuccinate, AOT) and water, called reverse micelles, was developed. The optimum concentrations of AOT, water and pyrogallol for determining SOD-like activity were found to be 50 mM, 1.3 M, and 40 mM, respectively. After proving that pyrogallol autoxidation was mediated by the superoxide anion in that system, the SOD-like activity of 24 lipophilic antioxidants was measured. Cinnamon oil, gamma-oryzanol, extract of rosemary leaf, L-alpha-lecithin, and L-alpha-cephalin exhibited activity, although the activity of some antioxidants could not be measured because of the intense color or low solubility. PMID- 7787295 TI - Role of ornithine in urea synthesis in rats treated with thyroid hormone. AB - The purpose of this study was to find whether the regulation of urea synthesis was mediated through the activation of N-acetyglutamate synthesis by ornithine when the thyroid status was manipulated. Experiments were done on three groups of rats, given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU + T3, or neither PTU nor T3 (control). Urinary excretion of urea and the liver concentrations of ornithine and N-acetylglutamate in rats given PTU + T3 were significantly lower than in rats given PTU alone. The liver concentration of N-acetylglutamate was correlated with the liver concentration of ornithine (r = 0.920, p < 0.001). Ornithine administration (0.5 mmol/100 g body wt) elevated the liver concentration of N acetylglutamate in all three groups. The results suggest that the greater concentration of ornithine in the hypothyroid (PTU alone) rats is likely to increase the N-acetylglutamate concentration in liver and stimulate urea synthesis. PMID- 7787298 TI - The complete amino acid sequence of chitinase-B from the leaves of pokeweed (Phytolacca americana). AB - The complete amino acid sequence of pokeweed leaf chitinase-B (PLC-B) has been determined by first sequencing all 19 tryptic peptides derived from the reduced and S-carboxymethylated (RCm-) PLC-B and then connecting them by analyzing the chymotryptic peptides from three fragments produced by cyanogen bromide cleavage of RCm-PLC-B. PLC-B consists of 274 amino acid residues and has a molecular mass of 29,473 Da. Six cysteine residues are linked by disulfide bonds between Cys20 and Cys67, Cys50 and Cys57, and Cys159 and Cys188. From 58-68% sequence homology of PLC-B with five class III chitinases, it was concluded that PLC-B is a basic class III chitinase. PMID- 7787297 TI - Alpha-subunit of beta-conglycinin, an allergenic protein recognized by IgE antibodies of soybean-sensitive patients with atopic dermatitis. AB - One of the major allergenic proteins in the soybean 7S-globulin fraction, which was recognized by sera of about 25% soybean-sensitive patients with atopic dermatitis, was identified as alpha-subunit of beta-conglycinin. The IgE antibodies recognizing the alpha-subunit did not show a cross-reactivity against both alpha'- and beta-subunits known to be highly homologous to alpha-subunit, and also against other allergenic components identified in soybeans [Ogawa et al., J. Nutr. Sci. Vitaminol., 35, 555-565 (1993)]. The IgE-binding site(s) was estimated to be located on the peptide 232-283 of alpha-subunit. PMID- 7787299 TI - Rapid and simple procedure for purifying PAS-4 glycoprotein from bovine milk fat globule membrane. AB - The isolation and partial characterization of PAS-4 glycoprotein (78 kDa) from bovine milk fat globule membrane (MFGM) is described. PAS-4 was selectively extracted with Triton X-114 nonionic detergent and then fractionated on DEAE Sepharose at pH 7.5. The PAS-4 fraction that was not bound on DEAE-Sepharose gave a single band by SDS-PAGE. The recovery of PAS-4 was 57.4% from MFGM. An amino acid analysis found a high percentage of nonpolar residues. Approximately 7.2% of carbohydrate from PAS-4 was composed of mannose, galactose (Gal), N acetylglucosamine, N-acetylgalactosamine (GalNAc), and sialic acid, most of the Gal and GalNAc in PAS-4 being released after mild alkaline hydrolysis. This indicated that PAS-4 contained both N- and O-linked sugar chains in concordance with the results of lectin affinity. PAS-4 had apparent isoelectric points of 7.45, 7.41, and 7.32, but these were shifted to pI 7.47 by a neuraminidase treatment. The apparent molecular weight of PAS-4 after deglycosylation with N glycanase was approximately 57,000 by SDS-PAGE. PMID- 7787300 TI - Effects of the lipid-saccharide complex and unsaponifiable matter from sunflowers on liver lipid metabolism and intestinal flora in rats. AB - The effects of the flower lipid-saccharide complex and unsaponifiable matter (1 g/kg of diet) from the sunflower on liver lipid metabolism and intestinal flora was studied in rats given cholesterol-enriched diets. After six weeks of feeding, the microsomal cholesterol concentration in the liver had been significantly reduced with the sunflower diet. The ratio of cholesterol/phospholipid was also reduced by the sunflower diet. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the sunflower groups was significantly lower than that of the control group. There was no significant difference in the cholesterol 7 alpha hydroxylase activity, although this tended to increase with dietary sunflower consumption. The number of Bacillus in the cecum flora was significantly higher in the lipid-saccharide complex group than in the other groups, while Bifidobacterium and Eubacterium in the cecum flora was significantly higher in the unsaponifiable matter group when compared to the control group. These results suggest that the lipid-saccharide complex and unsaponifiable matter in the sunflower are related to liver cholesterol synthesis and intestinal flora. PMID- 7787301 TI - Comparison of o-phthalaldehyde modification of alpha-amylases from porcine pancreas and Bacillus subtilis with Taka-amylase A. AB - A fluorescent reagent, o-phthalaldehyde (OPA), competitively inhibited porcine pancreatic alpha-amylase (PPA) with Ki values of 0.7-0.9 mM, while alpha-amylase from Bacillus subtilis (BS) was uncompetitively inhibited, with Ki values of 5.8 7.6 mM. In both cases, OPA gave a time-dependent irreversible inactivation, where the amylase activity was lost faster than the maltosidase activity. Zymograms of the course of OPA modification showed that PPA was converted into at least six, faster moving components and BS gave two components. The OPA modification was retarded by the addition of the substrate analog, cyclodextrins, and the OPA modified enzymes decreased in affinity for the substrate soluble starch. Stoichiometric measurement showed that both PPA and BS was inactivated by the incorporation of 1 mol of OPA per mol of enzyme. The role of OPA modification of alpha-amylases was discussed in relation to the regulation of catalytic activity of enzymes. PMID- 7787302 TI - Promoinducin, a novel thiopeptide produced by Streptomyces sp. SF2741. AB - Our continued screening to find tipA promoter-inducing substances resulted in the isolation of promoinducin from a mycelial extract of Streptomyces sp. SF2741. Based on various 1D- and 2D-NMR studies, including field gradient (FG)-COSY, HSQC, FG-HMBC, phase-sensitive 13C-decoupled HMBC and NOESY experiments, promoinducin's structure was established to be a thiopeptide composed of threonine, some unusual amino acids masked at their carboxyl groups by thiazole or methyloxazole rings, sulfomycinamate and five dehydroalanine residues. Promoinducin induced the tipA promoter at 40 ng/ml, and also exhibited strong antibacterial activity against some Gram-positive bacteria. PMID- 7787303 TI - Pyromeconic acid and its glucosidic derivatives from leaves of Erigeron annuus, and the siderophile activity of pyromeconic acid. AB - 3'-O-Caffeylerigeroside (pyromeconic acid 3-O-beta-D-glucoside 3'-O-caffeyl ester) was obtained from the leaves of Erigeron annuus as a new pyromeconic acid derivative, and its structure was elucidated. Together with the gamma-pyrone derivative, pyromeconic acid (3-hydroxy-4H-pyran-4-one) and its beta-glucoside (erigeroside) were also isolated from the aerial parts of E. annuus. The siderophile activity of pyromeconic acid was also studied. PMID- 7787304 TI - Selective use of L-valine and L-isoleucine for the biosynthesis of branched-chain fatty acids in rat skin. AB - Iso- and anteiso-fatty acids are detected in more than trace amounts in rat skin surface lipid. The terminal portion of even carbon number iso- and anteiso-fatty acids are synthesized respectively from valine (Val) and isoleucine (Ile) by essentially the same reaction sequences established for straight chain fatty acids. This paper describes the stereospecific biosynthesis of these branched chain fatty acids (BCFAs) and alcohols (BCFALs) in rat skin. Dependence of the concentration of these BCFAs on dietary L-Val and L-Ile was studied. Concentrations of even carbon number iso- and anteiso-fatty acid increased respectively with dietary L-Val and L-Ile. The saturation dose appeared to be 2% for L-Val and 1% for L-Ile. Supplementation of the diet with 2% D-Val, however, did not affect the concentration of even carbon number iso-fatty acid in rat skin surface lipid despite a comparable serum Val level to that of the 2% L-Val group. A similar experiment using 1% DL-Ile found that L-isomer, but not D-isomer, in the circulation was used for the biosynthesis of anteiso-fatty acids. This view was applicable to the incorporation of D-Val and DL-Ile into related BCFALs. PMID- 7787305 TI - Cleavage of connectin by calpain and cathepsin D. AB - mu-Calpain quickly split the alpha-connectin in myofibrils into beta-connectin, and then produced a 1700-kDa component. Cathepsin D also split alpha-connectin into beta-connectin, further degrading it to fragments smaller than the 1700-kDa component with increasing incubation time. The action of cathepsin D on the connectin molecule was distinctly different from that of mu-calpain in terms of the splitting rate and manner. When freshly excised muscle was exposed to a temperature of 37 degrees C, complete disappearance of connectin (alpha, beta and 1700-kDa component) was observed within 36 h. In contrast, at 2 degrees C, about 75% of connectin was retained as beta-form even after 3 weeks. The present data suggest that the degradation of connectin in muscle might be caused by mu-calpain in the early stage of aging, and then with time, this action is replaced by m calpain or cathepsin D. However, the possibility of other intrinsic proteases participating in the degradation of connectin still remains. PMID- 7787306 TI - A 3-deazauracil-resistant mutant of Bacillus subtilis with increased production of cytidine. AB - Bacillus subtilis No. 344 is a cytidine-producing mutant strain derived from wild type strain No. 122. When 3-deazauracil-resistant mutants were derived from strain No. 344, some of the mutants had higher productivities of cytidine. Among them, strain No. 428 accumulated 14.2 mg/ml cytidine in the culture. Cytidine 5' triphosphate (CTP) synthetase from strain No. 428 changed to be free from feedback inhibition by CTP, compared with the enzyme from strain No. 344. PMID- 7787310 TI - Isolation of bacteria degrading carbazole under microaerobic conditions, i.e. nitrogen gas substituted conditions. AB - Microorganisms degrading carbazole (CA), a model substrate of heterocyclic nitrogen compounds in crude petroleum oil, were screened under microaerobic conditions, i.e. nitrogen gas substituted conditions. Eight bacteria were isolated and identified. For example, Bacillus sp. KUKK-4 degraded 31% of CA when cultivated for 28 days in a medium initially containing CA at 1000 mg/l with shaking under the microaerobic conditions. PMID- 7787307 TI - Purification and characterization of membrane-bound hydrogenase from a thermophilic hydrogen-oxidizing bacterium, Pseudomonas hydrogenothermophila strain TH-1. AB - A membrane-bound hydrogenase was purified aerobically by one step using a hydroxyapatite column after solubilization by acetone treatment from a thermophilic hydrogen-oxidizing bacterium, Pseudomonas hydrogenothermophila strain TH-1. The enzyme consists of two polypeptides of 63 and 31 kDa, respectively. The amino-terminal amino acid sequences of both subunits were homologous to membrane-bound type [Ni-Fe] hydrogenases from other origins. The thermostability under a hydrogen gas atmosphere is highly stable at 50 degrees C, which is the optimum temperature for the cell growth. PMID- 7787308 TI - Functional distinction among structural subsections in the specific priming signal for DNA replication of the broad host-range plasmid RSF1010. AB - To analyze the functional contribution to the ssiA function of subsections of the ssiA-determinant sequence based on their dimensions, we constructed ssiA mutants carrying insertions and deletions. Results of the examination of the ssiA mutants told us that, in addition to the base sequence, the dimensions were crucial factors for the functional contribution of the subsections of ssiA. PMID- 7787311 TI - Binding of amino acid pyrolysates and aflatoxins to autoclaved cells of Enterococcus faecalis FK-23. AB - There was significant binding in autoclaved cells of Enterococcus faecalis FK-23 toward Trp-P1 and Trp-P2. Although the binding ability towards aflatoxins B1, B2, G1, and G2 was less compared with the significant binding toward Trp-P1 and Trp P2, higher percentage binding toward these aflatoxins was observed when the amount of the cell preparation was increased. PMID- 7787309 TI - USF-19A, a new lipoxygenase inhibitor from Streptomyces sp. AB - USF-19A, a soybean lipoxygenase (SBL) and human 5-lipoxygenase (5-LO) inhibitor, was isolated from Streptomyces sp. USF-19 strain. Its chemical structure was determined by spectroscopic evidence to be a new member of the antimycin antibiotic family. The IC50 value of USF-19A against 5-LO was 28.0 microM. PMID- 7787312 TI - Stimulatory factors for enzymatic biotin synthesis from dethiobiotin in cell-free extracts of Escherichia coli. AB - The activity of biotin synthesis from dethiobiotin was found in cell-free extracts of an Escherichia coli bioB transformant. Among the sulfur compounds tested, only S-adenosyl-L-methionine (AdoMet) had a significant effect, while methionine and cysteine were inert. The activity was linearly stimulated by increasing protein concentration. When the dialyzed cell-free extracts were used for the reaction, NADP+, NADPH, and FAD among the well-known cofactors tested promoted the activity. Furthermore, in the presence of AdoMet, cysteine was apparently effective for biotin synthetic activity. PMID- 7787313 TI - The phylogeny of Williopsis salicorniae Hinzelin, Kurtzman et Smith based on the partial sequences of 18S and 26S ribosomal RNAs (Saccharomycetaceae) AB - Williopsis salicorniae IFO 10733 (type strain), which is characterized by the formation of saturn-shaped ascospores, by the incapability of assimilating nitrate, and by a lower DNA base composition (36.7 mol% G + C), was examined for its partial base sequences of 18S and 26S rRNAs. In the 18S rRNA partial base sequencings, it had an identical base sequence with the type strain of Ogataea glucozyma (identical to Pichia glucozyma, identical to Hansenula glucozyma), which produces hat-shaped ascospores and has the ability to assimilate nitrate and methanol and a higher DNA base composition (45.1 mol% G + C). In the 26S rRNA partial base sequencings, the base differences were four, and the percent similarity was 87 between the type strains of the two species. The data obtained are discussed phylogenetically and taxonomically. PMID- 7787314 TI - Molecular cloning of a cDNA for proctase B from Aspergillus niger var. macrosporus and sequence comparison with other aspergillopepsins I. AB - A cDNA for proctase B from Aspergillus niger var. macrosporus was isolated and sequenced. The deduced amino acid sequence (394 residues) of the preproform of the enzyme was highly homologous (98% identify) with those of aspergillopepsins I from A. awamori and A. saitoi, and moderately homologous (68% identity) with that of A. oryzae. Most of the sequence differences were found in the carboxyl terminal domain. PMID- 7787316 TI - Event-related potential components analysis of cognitive impairment in patients with multiple lacunar infarcts. AB - We measured the visual event-related potentials (ERPs) and reaction time (RT) in 21 patients with multiple lacunar infarcts and in 8 age-equivalent normal subjects. The N2 latency of the infarct patients was significantly longer than that of the normal subjects, although the NA and the P3 latencies and RT did not differ between the two groups. The N2 latency was negatively correlated with the scores of Mini-Mental State Examination or the Hasegawa's dementia scale. These results suggest that the impairment of cognitive information processing in these patients arises from an uncertainty in the classification of a perceived event. In addition, the N2 latency may be more sensitive in detecting cognitive impairment in multiple infarct patients. PMID- 7787315 TI - Hepatic role in the storage and utilization of fish oil fatty acids in humans: studies on liver surgery patients. AB - Fish oil fatty acids (FOFA) were analyzed in fresh liver tissue and in subcutaneous and omental adipose tissue obtained from 5 patients who underwent partial hepatectomy. FOFA were also determined in plasma from 5 patients and in 10 healthy subjects. There was a high content of FOFA in the liver phospholipid (PL) fraction (twice that in our previous autopsy study) suggesting that these surgery patients had a hepatic FOFA content of at least 25g. In plasma, FOFA was predominantly found in the PL of high density lipoprotein (HDL) and partly in the PL of other lipoproteins. Since these lipoproteins are produced by the liver, the present findings indicate the role of the liver not only in storage but also in the utilization of FOFA to form the biologically important surface PL component of circulating lipoproteins. PMID- 7787317 TI - TRH stimulation test in healthy elderly: paradoxical response of growth hormone is abnormal in normal aging. AB - The purpose of this study was to measure TSH (thyrotropin), PRL (prolactin) and GH (growth hormone) response to a TRH (thyrotropin releasing hormone) stimulation test in 37 healthy elderly male subjects and determine if these responses correlate with the incidence of mental decline; and also, to determine if these responses occur more frequently in the elderly than in the general population. A hyperresponse of TSH was documented in 7 of our 37 elderly male subjects, a delayed response of TSH in 4, a low response of PRL in 29 and a significant paradoxical response of GH in 2. Those subjects with a significant paradoxical response of GH were 82 and 83 years of age and their HDS was 20.0 and 25.5, respectively. We did not find a causal relationship between mental decline and the paradoxical response of GH, but our data suggests that the paradoxical response of GH is not normal in elderly older than 80 years old. PMID- 7787318 TI - Portal hypertensive colopathy: endoscopic findings and the relation to portal pressure. AB - Portal hypertensive colopathy (PHC) is a new clinical entity in patients with liver cirrhosis. In this study, colonoscopic findings and clinical features including upper gastrointestinal endoscopy and hepatic hemodynamics were prospectively investigated among 35 PH patients with a hepatic venous pressure gradient (HVPG) of greater than 12 mmHg due to chronic liver diseases. Colonoscopy was also performed in 100 patients without liver disease as non-PH controls. The colonoscopy revealed vascular ectasias, vascular irregularity, vascular dilatation, solitary red spots, diffuse red spots, and hemorrhoids in 26, 32, 30, 25, 10 and 25, respectively, of 35 PH patients compared to 3, 7, 3, 11, 0 and 19, respectively, in controls. PHC was endoscopically diagnosed in 27 of 35 PH patients according to our criteria. These patients with PHC were more frequently associated with esophageal varices and portal hypertensive gastropathy, and had higher HVPG than PH patients without PHC. Portal hypertension is an important factor in the etiology of PHC. PMID- 7787319 TI - Thrombomodulin in exercise-induced asthma. AB - Thrombomodulin (TM) is a membrane protein present in the vascular endothelium. It has also been found in human plasma, within which, however, its pathological functions have not been clearly described. In this study, the plasma TM concentrations in 19 asthmatic patients were determined by sandwich enzyme immunoassay using two monoclonal antibodies for human TM. The concentration of plasma TM in exercise-induced asthma (EIA)-positive asthmatic patients was significantly increased by exercise challenge. In addition, for these patients a positive correlation was found between the severity of EIA and the degree of change in plasma TM induced by exercise challenge. These findings suggest that the increase in influx of TM into the plasma in EIA-positive asthmatics may be due to generalized pulmonary endothelial damage following exercise challenge. PMID- 7787320 TI - Parvovirus infection and generalized edema in adults. AB - We describe the clinical and laboratory findings of 7 adult patients with serological evidence of recent human parvovirus B19 (HPV) infection who presented with generalized edema. Six of the 7 patients had household contact with children with erythema infectiosum and had flu-like symptoms before visiting hospital. The interval between the flu-like episode and the development of edema ranged from 4 to 13 days (mean 7.0). In all 7 patients, there was serological confirmation of recent HPV infection, and all showed the development of edema following HPV infection without urine abnormalities or anemia. Two patients presented hypocomplementemia, and two patients showed signs of congestive heart failure. HPV may be considered a causative agent of generalized edema not only in the fetus but also in adults and HPV infection should be included in the differential diagnosis of generalized edema formation. PMID- 7787321 TI - Cytoplasmic body myopathy with hypertrophic cardiomyopathy. AB - A patient with cytoplasmic body myopathy presented muscle hypotonia from birth and developed progressive muscular atrophy and weakness, scoliosis, contracture of joints and cardiorespiratory failure. At the age of 17, he died of heart failure. Post mortem examination revealed severe hypertrophy of cardiac walls and generalized muscular atrophy. Microscopic examination showed many cytoplasmic bodies in skeletal muscle fibers and myofiber disarray in myocardium. No cases of cytoplasmic body myopathy with hypertrophic cardiomyopathy have been reported previously. It is suggested that the Z-line component is related to the formation of the cytoplasmic body in skeletal muscle and disarray in the cardiac muscle. PMID- 7787322 TI - Coronary thrombosis induced by intracoronary acetylcholine injection in a patient with normal coronary myocardial infarction. AB - A 67-year-old male was admitted with acute myocardial infarction. Coronary thrombolysis was carried out because complete occlusion of the obtuse marginal branch (OM) in the circumflex artery was detected in emergent coronary angiography, and recanalization of the OM was obtained at 3 hours after the onset of chest pain. No significant stenosis of the OM was found in coronary angiography performed at the recovery stage. After intracoronary acetylcholine injection to the left coronary artery, coronary spasm was induced and coronary thrombosis was observed in the left anterior descending artery thereafter. These findings indicate the possibility that the etiology of myocardial infarction is coronary thrombosis induced by coronary spasm. PMID- 7787323 TI - Appropriate intravenous doses of L-thyroxine and magnesium in a thyroidectomized patient with thyroid and parathyroid carcinomas receiving total parenteral nutrition during acute necrotizing pancreatitis. AB - A totally thyroidectomized patient with thyroid and parathyroid carcinomas, which had developed after neck irradiation in childhood, became hypercalcemic due to pulmonary metastases. The hypercalcemia was ameliorated by intermittent iv administration of bisphosphonate for 3.5 years, but this gradually became refractory to the bisphosphonate treatment. After right thoracotomy for resection of pulmonary metastases, acute necrotizing pancreatitis developed. The patient was therefore placed on total parenteral nutrition supplemented with T4 and a restricted dose of magnesium. Thyroxine(T4) (30 micrograms/day, iv) was not sufficient to maintain euthyroidism, but a higher dose (60 micrograms/day) elicited mild hyperthyroidism to the same extent as that elicited by an oral dose of 100 micrograms/day. The present case showed that the appropriate iv dose of T4 in this thyroidectomized patient with acute pancreatitis was about 60% of the oral dose. Furthermore, bisphosphonates (pamidronate and alendronate) and magnesium depletion were very effective in controlling the hypercalcemia. PMID- 7787324 TI - Acromegalic gigantism with low serum level of growth hormone and elevated serum insulin-like growth factor-I. AB - In a case of acromegalic gigantism with hyperprolactinemia is reported, the basal serum growth hormone (GH) levels ranged from 1.2 to 1.9 ng/ml. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood sampling showed non-pulsatile GH secretion. Serum prolactin and insulin-like growth factor-I (IGF-I) levels were elevated. After unsuccessful surgery, bromocriptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide with bromocriptine reduced serum GH and IGF-I levels. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF I and cause clinical acromegalic gigantism. PMID- 7787325 TI - Involvement of the central nervous system in rheumatoid arthritis: its clinical manifestations and analysis by magnetic resonance imaging. AB - A rheumatoid arthritis (RA) patient showed high signal intensity in the subcortical region of the frontal and occipital lobes on T2-weighted magnetic resonance imaging (MRI). Histopathological examination in the autopsy specimen revealed severe systemic vasculitis. Additional radiological and laboratory studies revealed that transient cerebral ischemia induced by vasculitis occurred in this patient. PMID- 7787327 TI - Collagenous colitis. AB - Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by colonic mucosal subepithelial collagen deposition. We report a 72-year-old woman who had collagenous colitis associated with chronic watery diarrhea. She received a non-steroidal anti-inflammatory agent (sulindac) because of rheumatoid arthritis. Histological examination of biopsy showed a thick subepithelial collagen layer with lymphocytes, plasma cells, and infiltration of a few eosinocytes in the lamina propria. These findings led to the diagnosis of collagenous colitis. After treatment with salazosulfapyridine, her bowel movement became normalized and mucosal subepithelial collagen deposition disappeared. PMID- 7787326 TI - Primary malignant lymphoma of the liver associated with cirrhosis induced by hepatitis C viral infection. AB - We present a case of primary malignant lymphoma of the liver of B cell origin with cirrhosis induced by hepatitis C viral infection. A 75-year-old Japanese woman with chronic liver dysfunction was admitted for hepatic tumors. The tumors were hypoechoic on ultrasonography and hypodense on computed tomography. Antibody to hepatitis C virus was positive. Ultrasonically guided biopsy was performed, and we diagnosed hepatic lymphoma with cirrhosis induced by hepatitis C virus clinically and immunohistochemically. This case may be the first report of the association of these two diseases, and may provide additional evidence of a predisposition to malignancy in cirrhosis. PMID- 7787328 TI - Aneurysmal dilatation of the pulmonary trunk with mild pulmonic stenosis. AB - We present the unusual case of a 72-year-old woman whose chest X-ray showed an abnormal left hilar shadow. A pulmonary angiogram revealed an aneurysm in the pulmonary artery with a diameter of 55 mm that extended from the main pulmonary trunk to its bifurcation. Mild pulmonic stenosis with a systolic pressure gradient of 18 mmHg across the pulmonic valve was recognized. Mild dilatation of the ascending aorta was also present. The pressure gradient across the pulmonic valve was lower than is typical for an aneurysmal dilatation, suggesting that this patient represented a case of idiopathic pulmonary artery dilatation. We suspected the presence of a congenital structural alteration common to the pulmonary artery and the ascending aorta. PMID- 7787329 TI - Virus-associated hemophagocytic syndrome due to measles accompanied by acute respiratory failure. AB - An 18-year-old male who was admitted to hospital due to fever, skin rashes, cough, and malaise showed laboratory examination findings of leukopenia, thrombocytopenia, mild liver dysfunction, and hypoxia. Bone marrow aspiration revealed 2% histiocytes with hemophagocytosis. Chest X-ray showed bilateral diffuse interstitial pneumonia. The titer of anti-measles virus antibody was < 1:4, and that at convalescence stage was 1:64. He was diagnosed as having hemophagocytic syndrome and acute respiratory failure due to measles, and was treated with methylprednisolone pulse therapy. He promptly recovered from thrombocytopenia and acute respiratory distress. Steroid pulse therapy may be effective in these conditions due to measles. PMID- 7787330 TI - Enlargement of multiple cavernous hemangioma of the liver in association with pregnancy. AB - Four cavernous hemangiomas were found in a 34-year-old woman after the first delivery. All four hemangiomas became enlarged after the second delivery. Due to complaints of symptoms of compression, and to rule out malignancy, surgical intervention was employed. Histologically, the tumors were typical cavernous hemangiomas. Although a relationship between enlargement of hemangiomas and estrogen was suggested, estrogen receptors were not detected in the tumors. PMID- 7787331 TI - Pneumatosis cystoides intestinalis after chemotherapy for hematological malignancies: report of 4 cases. AB - Pneumatosis cystoides intestinalis (PCI) is known to be a relatively rare condition which is characterized by gas cysts in the gastrointestinal mucosa. We treated four cases of PCI accompanied by hematological malignancies during chemotherapy treatment. All cases suffered from abdominal discomfort. Abdominal X ray films revealed gas cysts in the intestine. PCI was observed during leukocytopenic states, and three cases had septicemia. Etoposide was administered to three cases, and prednisolone to all cases. It is considered that PCI sometimes occurs in patients with hematological malignancies during a period of leukocytopenia, and may be caused by intestinal mucosal damage due to myelosuppressive agents and immunosuppression from prednisolone. PMID- 7787332 TI - Von Hippel-Lindau disease with multiple spinal cord hemangioblastomas, syringomyelia and pheochromocytoma. AB - A 31-year-old blind man presented with numbness and weakness in the left hand, and elevated blood pressure. Multiple hemangioblastomas in the spinal cord associated with syringomyelia were well demonstrated by gadolinium-enhanced magnetic resonance imaging (MRI). He also had pheochromocytoma in the right adrenal gland, which was disclosed by abdominal computed tomography, MRI and 131I metaiodobenzylguanidine scintigraphy. MRI screening should be considered for patients with von Hippel-Lindau gene to detect the multiple lesions in this disease. PMID- 7787333 TI - Determination of a common clonal origin of gastric and pulmonary mucosa associated lymphoid tissue lymphomas presenting five years apart. AB - Mucosa-associated lymphoid tissue (MALT) lymphoma is often mis-diagnosed as a benign tumor. Dissemination to other sites occurs in MALT lymphoma. We report a 60-year-old man with gastric and pulmonary tumors of MALT lymphoma which occurred 5 years apart. Initially, the gastric tumor had been diagnosed as reactive lymphoreticular hyperplasia. To determine whether the two tumors arose from the same malignant clone, we amplified and sequenced the complementarity-determining region 3 of the immunoglobulin heavy chain gene using the polymerase chain reaction (PCR). The sequences were identical except for 11-nucleotide difference, suggesting identical clonality. PMID- 7787334 TI - Abrupt-onset diabetes mellitus in the elderly. AB - We present three elderly Japanese patients with abrupt onset of diabetes mellitus: a 61-year-old male with a complete defect of insulin secretion without insulin resistance, a 60-year-old male with an incomplete defect of insulin secretion associated with insulin resistance, and a 69-year-old female with a complete defect of insulin secretion and insulin resistance. The findings in these cases indicate the heterogeneity in insulin secretion and sensitivity of abrupt onset diabetes mellitus in the elderly. The changes in insulin secretion and sensitivity over time due to glucose toxicity may at least partially explain the heterogeneity. PMID- 7787336 TI - Predicting subsequent employment status of SSA disability applicants with chronic pain. AB - OBJECTIVE: The study assessed the predictive ability of the standardized Multiperspective Multidimensional Pain Assessment Protocol (MMPAP). An assessment tool that predicts return to work with chronic pain patients is needed, as increasing numbers of disability applications are adjudicated in the courts. DESIGN: National randomized validation sample of disability applicants. Each MMPAP consisted of physical examinations by two physiatrists and the participant's subjective assessment. Criterion standards were Multidimensional Pain Inventory and McGill Pain Questionnaire. There was phone follow-up 6 months postdecision. SETTING: Six clinical sites were ambulatory referral centers, both public and private. PARTICIPANTS: Population-based random national sample of 710 Social Security disability applicants claiming chronic pain related to their disability, stratified by national Social Security Administration (SSA) applicant demographics. Seventy-eight were lost to follow-up, and 688 initially refused. INTERVENTIONS: No interventions were continued or initiated by the research team between assessment and follow-up. MAIN OUTCOME MEASURES: Claimant employment status 6 months after disability decision was primary outcome, change in pain intensity, and change in employment situation. RESULTS: The MMPAP predicted with 90% accuracy employment status of SSA disability applicants with chronic pain 6 months postdecision when assessed at application by two physicians trained in Physical Medicine and Rehabilitation (physiatry). Accuracy of employment situation change was 93%, and pain intensity change was 65%. Self-report measures, physical examination results, psychological status, functional limitations, and physician's subjective appraisal predict future employment. CONCLUSIONS: The MMPAP accurately predicts future employment of disability applicants claiming chronic pain. The introduction of this standardized protocol will assist in standardizing disability determination for claimants with chronic pain. PMID- 7787337 TI - Pain in young adults. II: The use and perceived effectiveness of pain-coping strategies. AB - OBJECTIVE: The first goal of the study was to determine the internal reliability of the Coping Strategies Questionnaire (CSQ) in young adults. The second goal was to examine the relation of the CSQ to reported pain levels. The third goal was to investigate the relationship between the CSQ and concomitant pain problems. The fourth goal was to compare young adults and different chronic pain samples in terms of the frequency of coping strategy use and perceived effectiveness of coping strategies. DESIGN: The study included 252 undergraduate students who were given the CSQ, a demographic and pain level questionnaire, and a concomitant pain problem survey. RESULTS: The results indicated that the CSQ was internally reliable when used to assess pain coping strategy use among young adults. Catastrophizing was found to be associated with both pain level and concomitant pain problems, with subjects reporting higher levels of catastrophizing having higher levels of pain and a higher frequency of both migraine headaches and low back pain. Finally, differences were found when comparing the perceived effectiveness in controlling and decreasing pain, and in the use of specific coping strategies in the young adult and chronic pain samples. The young adult sample reported a greater perceived efficacy in controlling and decreasing pain, compared to a sample of low back pain patients and a sample of myofacial pain patients. CONCLUSIONS: The results indicate that the CSQ is a reliable measure for the study of pain-coping strategies used in this population, and one that relates to differences reported in the experience of pain. PMID- 7787335 TI - The curate's egg. PMID- 7787338 TI - Secondary gain concept: a review of the scientific evidence. AB - The "secondary gain" concept originated in the psychoanalytic literature, where it was never vigorously examined. The purpose of this review is to determine if there are scientific studies that have explored the validity of this concept. DESIGN: A computer and manual literature review yielded 166 references in which primary, secondary, and tertiary gain were mentioned. Twenty-four (14.5%) of these reports were "secondary gain" studies. Fourteen "reinforcement" studies were also found. These 38 studies were grouped according to topics and reviewed in detail. SETTING: Any medical treatment setting including pain treatment was utilized in the review procedure, i.e., no exclusion criteria. PATIENTS: Any patient type, including those suffering from chronic pain, were utilized in the review procedure, i.e., no exclusion criteria. RESULTS: A significant but limited number of studies have investigated the "secondary gain" concept, and the results of some of these studies are in conflict. Results of some studies, however, are remarkably consistent in supporting the importance of "secondary gain" to behavior. Some studies have methodological flaws, usually relating to how the presence of secondary gain was established. CONCLUSIONS: Overall the results of the reviewed studies support the potential importance of the "secondary gain" concept to understanding illness behavior and underscore a need for future research in this area. PMID- 7787339 TI - Painful neuropathy: C-nociceptor activity may not be necessary to maintain central mechanisms accounting for dynamic mechanical allodynia. AB - OBJECTIVE: In neuropathic pain states, dynamic mechanical allodynia is mediated by large diameter A beta-fibers. We test whether ongoing peripheral C-nociceptor input is necessary to maintain central changes hypothetically responsible for A beta-mediated allodynia. CASE REPORT: A patient with long-standing diabetes mellitus demonstrated generalized signs of painless diabetic small fiber polyneuropathy. Following mechanical trauma, the patient additionally developed a typical neuropathic pain syndrome at the arm. Despite substantial impairment of cutaneous small fiber function, he complained of severe dynamic mechanical allodynia confined to a forearm skin area. METHODS AND RESULTS: Marstock test revealed a considerably increased cold perception threshold within the allodynic area and on the contralateral side. The patient could not perceive any warm sensation on either side. Histamine iontophoresis was not followed by any itch or pain sensations within the allodynic area or contralaterally. Nociceptive C-fiber axon reflex reactions were substantially impaired within the allodynic skin or contralaterally. Standard neurophysiological testing and quantitative vibrametry showed only mild impairment of large diameter sensory and motor fiber function at the arms. Cardiovascular reflex tests showed almost no heart rate variation indicating impairment of vagal small fiber function. CONCLUSIONS: (a) Cutaneous nociceptive C-fibers do not signal dynamic mechanical allodynia. This symptom may hypothetically be due to secondary changes in the central nervous system processing that might strengthen the synaptic ties between A beta-fibers and central nociceptive pathways, or due to peripheral multiplication of primary afferent low threshold mechanoreceptor input. (b) Ongoing nociceptive C-fiber input is not necessary to maintain either hypothetical mechanism. (c) Hypothetical secondary central hyperexcitability might work autonomously without any nociceptive C-fiber input for a long time or even indefinitely in some neuropathic patients. PMID- 7787340 TI - Is diabetic autonomic neuropathy protective against reflex sympathetic dystrophy? PMID- 7787341 TI - The nature of myofascial trigger points. PMID- 7787343 TI - MR imaging evaluation of the spine with titanium alloy pedicular screw fixation. AB - We studied the cases of 60 patients who underwent magnetic resonance (MR) imaging evaluation after fixation with the titanium alloy pedicular screw system. Spine stabilization was required in the thoracic and lumbar region for various spinal disorders. The images were evaluated for the spinal and adjacent tissues. These pedicular screw systems were imaged safely and caused no particular clinical problems. The localized signal void artifacts were seen around the implants. This artifact did not interfere with the diagnosis for another disease. The spinal cord and dura mater appeared in midsagittal and in axial images except for regions lying close to the implants. After surgery MR imaging revealed the decompressed or the deformed spinal cord. However, the prognosis of spinal disorder could not be revealed by the intensity grade of MR imaging because of the distortion in the spinal cord. PMID- 7787342 TI - The application of Diapason spinal fixator device: a comparison with the Steffee VSP plate. AB - Twenty-five consecutive patients who had a variety of lumbar disorders and who underwent lumbar spinal fusion using the Diapason fixator were followed for a mean period of 20 months. The operations included 16 posterior lumbar interbody fusion (PLIF), 7 posterolateral fusion (PLF), and 2 combined PLIF and PLF (PLIF/PLF). As a control group, 38 patients undergoing PLIF using a Steffee VSP plate (VSP) were followed for a mean period of 24 months. There were no significant differences between the two groups regarding the operation time, blood loss, and improvement of preoperative symptoms. However, incidence of incomplete bony union and radiolucent zone around the screws were higher in the Diapason group than in the VSP group. Our study suggests that there was a possibility of insufficient rigidity of screw-rod fixation in the Diapason system. PMID- 7787345 TI - Hydroxylapatite-coated Diapason screws: first clinical report. AB - We report our preliminary experience with 27 patients who underwent surgery for posterior spinal arthrodesis using the hydroxylapatite-coated Diapason screws. Each of the patients was considered to have a condition that was mechanically risky from the surgical standpoint. The results were good for patients with lytic spondylolisthesis and were excellent for patients with osteoporosis, but were generally less successful for patients requiring "long lever arm" fixations and those with degenerative scoliosis. PMID- 7787344 TI - Clinical application of the Diapason hook system: a preliminary case report. AB - A preliminary case report of the clinical application of the Diapason hook system is discussed. The hooks were implanted in six patients for the fixation of the thoracic region (n = 3), the prevention of backout of pedicular screws (n = 3), and repair of the pars interarticularis (n = 1); the patients were followed for more than 6 months after the surgery. Results indicate that in all of the cases the initial purpose of the Diapason hook system was served. The advantages of the Diapason screw and hook system are its titanium alloy material and simplicity in implanting. Although there have been no instrument failures or any other complications, the cases need longer follow-up. In addition, the size of some hooks needs to be improved because they were too large to apply to the short segments. PMID- 7787346 TI - Lumbar spinal fusion using the Diapason system. AB - Lumbar spinal fusion with the Diapason system was performed on 58 patients at Toho University Ohmori Hospital from November 1991 to November 1994. The first 44 consecutive patients were followed for more than 1 year, including 34 cases with degenerative diseases. Those 34 cases consisted of 22 men and 12 women, ages 19 78 years (average 47.4), with 49 vertebral levels; these patients were followed for an average of 26.3 months. The clinical improvement and rate of bony union after 1 year of surgery were examined and the intervertebral angulatory motion degree of fused vertebrae was measured using a radiographic functional photo image during 1 year. We also performed an experimental study to evaluate the rigidity of this system. There were no severe complications. Although there was no instrument breakage or screw migration, two cases of rod migration were observed in L5-S1 arthrodesis. A mean improvement rate of 84.3% in the Japanese Orthopaedics Association (JOA) score was revealed. Thirty-three of 34 (97.1%) patients demonstrated successful arthrodesis after their initial procedure. In 10 segments (20.4%) 3-5 degrees of angulatory mobility were still retained, and no angulatory motion was observed in 27 segments (55.1%) 3 months after the surgery; however, no angulatory motion was observed in 44 segments (89.8%) 1 year after the surgery. In our biomechanical study, we observed that the anterior intervertebral space became narrow and mobile with loading, but when the loading was removed, the space reverted to the initial site. This movement was thought to be due to a certain elasticity in the rod and screw, and not loosening at the connection level. This system was evaluated based on the results of both clinical and biomechanical study. Notwithstanding the fact that this method has been evaluated as semirigid fusion, it does provide satisfactory bony union in posterolateral fusion, with excellent clinical results. PMID- 7787347 TI - Impact of different patency criteria on long-term results of femoropopliteal angioplasty: analysis of 106 consecutive patients with claudication. AB - PURPOSE: To assess the impact of different patency criteria on long-term results after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. PATIENTS AND METHODS: The results of femoropopliteal PTA in 106 consecutive patients with claudication (140 treated limbs) were analyzed. The treated artery segment was considered patent if (a) the ankle-brachial index (ABI) had increased by more than 0.10 initially and not deteriorated by more than 0.15 from the maximum early postprocedural level and (b) the ABI was consistently at least 0.15 above the preprocedural level. The third criteria was based on patients' subjective assessment of patency. Initial failures were either included or excluded and both primary (the outcome of the original PTA) and secondary patency (also repeated PTAs included) were determined. RESULTS: When the different criteria were applied, the patency rates at 3 years ranged from 42% to 82% in this patient population. CONCLUSION: These results stress the importance of uniform criteria when results of different kind of vascular interventions are reported. PMID- 7787348 TI - Percutaneous transluminal angioplasty of visceral arterial stenoses: results and long-term clinical follow-up. AB - PURPOSE: To determine the efficacy and safety of percutaneous transluminal angioplasty (PTA) of the visceral arteries. PATIENTS AND METHODS: We retrospectively evaluated the results of PTA performed in 20 visceral arteries in 19 patients (10 men, nine women; mean age, 63 years). Eleven patients had symptoms characteristic of mesenteric ischemia, four had atypical abdominal pain, and four were undergoing prophylactic dilation before undergoing another procedure involving the abdominal aorta. Clinical follow-up was possible in all patients. RESULTS: PTA was technically successful in 15 of 19 patients (79%); among these 15 patients, 12 (80%) did well clinically. Of the seven PTA procedures that were immediate failures, five failed secondary to an occult malignancy or to extrinsic arterial compression by the median arcuate ligament. Ten (83%) of the 12 patients in whom the procedures were immediate clinical successes are still clinically improved at 4-73 months follow-up (mean, 25 months). PTA was successful in only one of the four patients who had symptoms atypical of mesenteric ischemia, but it was successful in 11 of the 15 patients who had symptoms of mesenteric ischemia or who underwent prophylactic dilation. Major complications occurred in three (16%) of the 19 patients. CONCLUSION: PTA of visceral artery stenoses is effective in patients with symptoms of mesenteric ischemia. It is also effective as prophylaxis in patients undergoing additional procedures in the abdominal aorta. PMID- 7787350 TI - Gastrostomy button placement through percutaneous gastrostomy tracts created with fluoroscopic guidance: experience in 27 children. AB - PURPOSE: The authors report their experience with skin level (button) gastrostomy placement through radiologically created gastrostomy tracts. PATIENTS AND METHODS: Fifty-two gastrostomy buttons have been placed in 27 children (average age, 73 months; range, 9-235 months). All buttons were placed through tracts created during earlier fluoroscopically guided percutaneous gastrostomy. Fifteen Bard mushroom-type buttons and 12 MIC-Key balloon-type buttons were initially placed. Patients have been followed up for an average of 13.4 months. RESULTS: Button placement was successful at the initial attempt in 25 of 27 patients (93%). Tract age at button placement averaged 18.5 weeks. The average tract length measured 3.5 cm (1.7-6.0 cm). Tract rupture and peritoneal leakage occurred in three patients; one patient had the button immediately repositioned without sequela, and the remaining two patients underwent replacement of the gastrostomy tube into the stomach and successful button placement approximately 1 week later. There were no major complications. Minor problems (leak, granulation tissue, valve malfunction, balloon breakage) occurred in 19 patients. CONCLUSION: Button gastrostomy is a useful alternative to the traditional gastrostomy tube for the pediatric population. Conversion with use of existing radiologically created tracts is possible and safe. Attention to tract integrity and proper button position is required to avoid complications. PMID- 7787349 TI - Use of the Palmaz stent in primary treatment of renal artery intimal injury secondary to blunt trauma. PMID- 7787351 TI - Peritoneal abscesses due to bowel perforation: effect of extent on outcome after percutaneous drainage. AB - PURPOSE: To determine the effect of extent of peritoneal contamination in enteric abscesses on final outcome and duration of percutaneous drainage. PATIENTS AND METHODS: Results were retrospectively reviewed for 11 patients with varying degrees of peritoneal contamination secondary to subacute bowel perforation who were primarily treated with percutaneous drainage. Stepwise linear regression analysis of duration of drainage was performed with use of patient age and immune status, the site of bowel perforation, and the number of peritoneal compartments involved in the resultant contamination as independent variables. RESULTS: In 10 of 11 patients (91%) treatment of the resultant intraperitoneal collections with percutaneous drainage was successful irrespective of the extent of peritoneal contamination. There was no correlation between duration of drainage and extent of peritoneal contamination but good correlation with patient age and site of bowel perforation (r = 0.82, P = .02). CONCLUSION: In patients with enteric abscesses due to subacute bowel perforation, the duration of drainage and final outcome after percutaneous drainage are independent of the extent of peritoneal contamination. PMID- 7787352 TI - Percutaneous management of external pancreatic fistulas: the use of articulated and metal stents. PMID- 7787355 TI - Treatment of acute mesenteric venous thrombosis with transjugular intramesenteric urokinase infusion. PMID- 7787353 TI - Experimental investigation of hypercoagulant conditions associated with angiography. AB - PURPOSE: To evaluate changes in blood coagulability after high-velocity intravascular fluid injections under conditions relevant to angiography. MATERIALS AND METHODS: In 101 rabbits, fluids were injected at 1,000 psi (6,890 kPa) via a multiple-side-hole catheter in the abdominal aorta, while blood was simultaneously aspirated via a second downstream catheter. The fluids injected included saline, contrast media, blood, tissue plasminogen activator, and heparin. The aspirate was evaluated for clotting time with an activated clotting time (ACT) device, for elevated levels of plasma hemoglobin to confirm capture of at least part of the injection bolus in the sample, and sometimes for hematocrit or fibrin degradation products (FDP). RESULTS: A single high-pressure injection of 2 mL of saline briefly accelerated the ACT of a blood-saline bolus (mean, 38% +/- 4). The mean volume of the hypercoagulable bolus was 15 mL. Systemic FDP levels became elevated within a few minutes after initial injection, suggesting activation of the fibrinolytic system by intravascular clot formation. Subsequent injections produced less hypercoagulability, probably reflecting the anticoagulant effects of FDP. Pressure-injected contrast agents had anticoagulant effects. The ACT was accelerated by up to 80% after injection of blood that had remained within the catheter for 3-10 minutes. Glove powder or gauze lint from wiping the guide wire markedly accelerated intracatheter clotting. Hypercoagulability after injection of clotting blood was partially prevented by injections with contrast agent and was completely inhibited by low-dose systemic heparinization. CONCLUSION: A hypercoagulable bolus may occur after angiographically relevant high-pressure fluid injections. The major contributing factors appear to be high jet velocities and injection of small amounts of clotting blood. Heparinization provides a simple and effective means of prevention. PMID- 7787354 TI - Thrombolytic therapy and balloon catheter thrombectomy in experimental femoral artery thrombosis: effect on arterial wall morphology. AB - PURPOSE: To determine vessel wall architectural changes after lytic therapy and balloon catheter thrombectomy in experimentally thrombosed arteries. MATERIALS AND METHODS: Bilateral 5-cm femoral artery occlusions were created by ligation in 14 dogs. Two dogs served as controls, and 12 animals underwent balloon catheter thrombectomy on the left and lytic therapy with urokinase on the right either 24 hours (group 1, n = 6) or 7 days (group 2, n = 6) after creation of the occlusion. After treatment, the area of thrombosis was subjected to light and scanning electron microscopy. RESULTS: The IEL was intact in all lysed arteries. IEL fractures were present in 11 of 12 arteries treated with thrombectomy. For group 1 arteries, average luminal area after thrombectomy was 5.63 mm2 +/- 0.66 versus 1.94 mm2 +/- 0.7 after lytic therapy (P < .007). Mean control artery luminal area was 2.86 mm2 +/- 0.52. Similar differences were found in group 2 arteries. With lytic therapy, scanning electron microscopy grading revealed surfaces to be intact in group 1, but moderate injury was exhibited in group 2. All arteries treated with thrombectomy had severe injury. CONCLUSIONS: Lysis of acute thrombi (group 1) preserved arterial wall architecture, with an intact IEL and no endothelial injury. Lysis of chronic thrombi (group 2) was associated with mild to moderate injury. Catheter thrombectomy caused severe injury regardless of the time of intervention. These results may help explain the poor long-term patency observed after these interventions. PMID- 7787358 TI - Angiographic embolization of the distal internal mammary artery as an adjunct to regional chemotherapy in inoperable breast carcinoma. PMID- 7787357 TI - Bleeding stomal varices: treatment with a transjugular intrahepatic portosystemic shunt in two pediatric patients. PMID- 7787359 TI - Use of a LeVeen shunt as a percutaneously placed abdominal drainage catheter for malignant ascites. PMID- 7787361 TI - The misplaced central venous catheter: a long loop technique for repositioning. PMID- 7787356 TI - Prevention of significant hemobilia during placement of transhepatic biliary drainage catheters: technique modification and initial results. AB - PURPOSE: The authors evaluated a technique for the prevention of significant hemobilia during placement of transhepatic biliary drainage catheters (TBDCs). PATIENTS AND METHODS: Twenty patients with strictures were randomized to two groups. In the control group, the biliary tree was accessed with an Accustick system and a TBDC was placed routinely. In the experimental group, following initial access, a rotating hemostatic valve was attached and the outer sheath was pulled back over the wire while contrast material was injected. If a major vascular structure was encountered, the tract was not used for TBDC placement. However, the outer sheath was re-advanced and used to opacify the ducts. This facilitated separate access. Once access was achieved without traversing a major vascular structure, a TBDC was placed, and the Accustick system was removed. If a portal vein or hepatic vein branch was traversed, no additional maneuvers were performed. However, if a branch of the hepatic artery had been traversed, the tract and biliary-arterial fistula were embolized with gelatin sponge pledgets. Both groups were evaluated for hemobilia for 6 weeks. RESULTS: In the control group, there were three cases of significant hemobilia; two were mild, one was severe. In the experimental group, the tract communicated with a major vascular structure in three patients. In these patients, a second access was used for TBDC placement. None of the patients in the experimental group experienced significant hemobilia. CONCLUSION: Visualization prevents the usage of tracts that communicate with large vascular structures. Initial results indicate that this reduces the frequency of significant hemobilia when TBDCs are placed. PMID- 7787360 TI - Radiologic placement of long-term central venous peripheral access system ports (PAS Port): results in 150 patients. AB - PURPOSE: The author reports experience with 150 peripheral access system ports (PAS Ports) placed in an interventional radiology suite. Complication rates from this series are compared with those of surgically placed tunneled catheters. The average cost of placement is compared with that of a surgically placed chest port. PATIENTS AND METHODS: Findings were retrospectively reviewed in 150 patients in whom the PAS Port catheter was implanted. The age range was 26-84 years (mean, 46 years). The diagnoses in these patients included cancer (n = 68), acquired immunodeficiency syndrome (n = 52), osteomyelitis (n = 21), and abscess (n = 9). Implantation with use of fluoroscopic guidance and "Cath-finder" technology is described. RESULTS: One hundred fifty ports have been indwelling for a total of 24,151 patient days (range, 40-220 days; mean duration, 161 days). Sepsis occurred in 3.3%, local infection in 5% (early infection 1%, late infection 4%), temporary catheter occlusion in 3.3%, postinsertion phlebitis in 7.3%, and venous thrombosis in 2%. The cost of radiologic PAS Port insertion averaged $1,488 versus $3,720 for surgical chest port insertion. CONCLUSION: PAS Port central venous catheter placement by an interventional radiologist in this series is safe and cost effective and compares very favorably with surgery. Radiologists will likely see increasing requests by referring physicians for radiologically placed catheters and ports in this era of cost containment. PMID- 7787362 TI - Graft-to-vein fistulas associated with polytetrafluoroethylene dialysis grafts: diagnosis and clinical significance. AB - PURPOSE: To describe the diagnosis and morphology of abnormal fistulas between dialysis grafts and adjacent native veins in five patients and to discuss their clinical significance. PATIENTS AND METHODS: Five patients with PTFE loop-type forearm dialysis grafts were found to have graft-to-vein fistulas in the presence of venous outflow stenosis or occlusion. Three patients underwent surgical revision and two patients underwent percutaneous angioplasty of the venous obstruction. Only one patient required ligation of the abnormal graft-to-vein fistula. The clinical history, dialysis records, surgical reports, and subsequent radiographs of the fistula were reviewed to determine the clinical significance of these fistulas. RESULTS: Two patients presented with partial graft thrombosis; the proximal portion of the graft remained patent due to persistent flow through the fistulous communication to an adjacent native vein. Two other patients had a graft-to-vein fistula arising from a pseudoaneurysm, which itself was originating from the graft. After either surgical or percutaneous treatment of the venous obstruction, all five grafts remained functional during the follow-up period. CONCLUSION: These iatrogenic, small-caliber fistulas are not uncommon but only manifest during periods of elevated graft pressure. Once the graft pressure is normalized, these fistulas have minimal hemodynamic effect and need not be specifically treated. PMID- 7787363 TI - Successful restoration of renal allograft function with urokinase thrombolysis in the setting of phlegmasia cerulea dolens. PMID- 7787364 TI - Phlegmasia cerulea dolens of the upper extremity. PMID- 7787365 TI - Endovascular credentialing. Endovascular Surgery Credentialing and Training Subcommittee. PMID- 7787366 TI - Foreign body retrieval with the braiding maneuver. PMID- 7787367 TI - Infusion catheter protection with use of an ostomy bag system. PMID- 7787368 TI - [Effects of the Health Structure Regulation on prescribing behavior of established physicians]. AB - In 1992 the German Federal Minister of Health enacted a new law to secure the health insurance system by budgeting the expenses for prescriptions among else. The data derived from a sample of computer-assisted private practices show a significant decline of prescriptions both in natural units and in value since 1993, but the analysis of the patients' data also reveals a more or less deliberate pattern of procedure followed by the GPs with regard to certain groups of patients such as elderly or chronically ill patients. PMID- 7787370 TI - [Measuring bone density--applications, critique, consequences]. AB - The supporters of bone density measurement or osteodensitometry claim that it is possible to reduce the frequency of fractures if a lack of systemic bone mineral content is detected in time. Important topical points of criticism are brought forward. Meaningful clinical use is only possible if reference data referring to population are accepted, and standardised quality assurance is safeguarded. Densitometrical methods do not guarantee sufficient prognostic data neither for diagnostic purposes nor for estimating the risk of fracture. In addition, they are not reliable enough for assessment of a treatment. The compensation of costs by statutory health insurance for bone density measurements as therapeutic aid should be restricted to regular controls of bone density after having diagnosed a pathological fracture, and to controls of certain secondary forms of osteoporosis. PMID- 7787369 TI - [Evaluation and utilization of complementary medical procedures--a survey of 793 physicians in general practice and the clinic]. AB - It is well known that complementary medicine is demanded by numerous patients and used by many doctors. In a representative postal survey of 793 female and male doctors working in practices and hospitals in the town and in the district of Kassel we could confirm the wide distribution of these procedures, especially as far as doctors in practice are concerned. It was the special interest of our study to analyse the motives for the use and the indications and to ask for a detailed and differential assessment of 18 complementary techniques. PMID- 7787371 TI - [Complete nutrition and social assistance]. AB - Additional supplementary benefits for nutrition are provided by social legislation; they are based on recommendations which have to be reconsidered in general as regards contents and quantities. The practice of assessment by Public Health Offices has no standardized regulations. Surveys have indicated that the recommendations are based on low-price calculations. The fundamental basis of supplementary benefits cannot guarantee healthy nutrition and therefore ignores the aim of prevention which had originally been included in social legislation. PMID- 7787372 TI - [Evaluation of impact on health--a central responsibility of the public health service]. AB - Health impact assessment (HIA) is defined in this paper as the adequate coverage of health aspects within the context of environmental impact assessment. HIA is a typical task for the public health service. A project on HIA undertaken by the North Rhine-Westphalian Research Compound for Public Health found out that presently the opportunity to use HIA for preventive health purposes is still largely neglected. However, in a survey local health departments expressed great interest in receiving HIA-training. A workable concept and supporting tools are both necessary prerequisites for the practice of HIA becoming routine. This paper presents a ten step HIA-conceptl. Supporting tools are presently under development and testing. PMID- 7787373 TI - [A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)]. AB - This pilot-study should contribute to the question whether Pyrethroid intoxication can be distinguished from other diseases by characteristic clinical symptoms. The results show that the characteristics of the intoxication do not consist in singular symptoms but in combinations and correlations of symptoms, i.e. of central-neurological with peripheral- and autonomic-neurological as well as with characteristic immunological disturbances. Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. Non-neurological symptoms include immunosuppression with consecutive opportunistic infections, like candida albicans, most frequently of the alimentary tract, but also dermal and mucosal swellings, lichen-ruber-like efflorescences, loss of hair, conjunctivitis. Other symptoms are: hypoglycaemic crises inhibition of fertility, disturbances of blood clotting, and most frequently in children, suspected hematopoetic disorders. PMID- 7787374 TI - [Frequency analysis for achieving health goals--II: Analysis of mortality tables for cause of death, expected mortality]. AB - The article gives algorithms to calculate mean ages at death for specific causes, based on life table models. Parameters of interest are death due to a specific cause, dying after the "elimination" of the specific cause, or the transition into a "new" structure of mortality when a specific cause of death vanishes. The setbacks of widely used calculations are discussed in this context. These different approaches are demonstrated by means of data pertaining to accident and cardiovascular mortality of the male population of Berlin (West). The estimated impact on life expectancy varies according to both the mathematical model and the specific cause of death: differences are negligible in mortality due to accidents, whereas the results differ considerably in cardiovascular causes of death. The algorithm suggested allows to constrain the calculations to specific age groups. Topics such as "avoidable death" and "health objectives" have to be aware of these different methods. PMID- 7787375 TI - [Medical aid according to the asylum application regulation--a report of experiences after the first year]. AB - In 1993 the Law Concerning Social and Medical Aid for People Asking for Political Asylum in the Federal Republic of Germany (Asylbewerberleistungsgesetz) was promulgated. In so far the main political aims of the new law are concerned it is to say that in the case of dental treatment they have failed at least in the first year. The author believes it to be more serious from a medical point of view that there is a tendency towards a medicine having two different "classes". PMID- 7787376 TI - [Women and Health--Perspectives in Epidemiology and Public Health Sciences, Symposium, Bremen 28 October 1994]. PMID- 7787377 TI - [Quality assurance in social medicine and as the responsibility of the German Society of Social Medicine and Prevention]. PMID- 7787379 TI - [Graduate education for the physician in public health, theoretical section at the Mecklenburg-Vorpommern Academy of Social Medicine]. PMID- 7787378 TI - [Report on the Physicians' Congress of Thuringen and Hessen Medical Services in Health Insurance 5 and 6 December 1994 in Weimar]. PMID- 7787380 TI - Employment, retirement and elderly persons with an intellectual disability. AB - A national Australian study of people with an intellectual disability of 55 years of age and over investigated their employment and retirement patterns, attitudes to work and retirement, and the degree to which they were involved in leisure or recreational programmes. Two cohorts were recruited: one included all known members of the target group who agreed to participate in the study in the states of Queensland and Western Australia; and the second was a proportional, random sample drawn from a national database on a state population basis. A large number of the participants had never been involved in full- or part-time employment, either in a competitive or supported environment, or in workshops. The majority of those who had worked expressed strong positive attitudes toward employment and concern about retirement, suggesting the need for pre-retirement programmes including transition and choice-making skills to prepare participants for the future. PMID- 7787381 TI - How do carers assess the severity of challenging behaviour? A total population study. AB - The severity of management problems of 13 types of problem behaviour presented by a total population sample of people with learning disabilities, as reported by their primary carers on eight separate assessments over 5 years, was examined. Three types of residential setting were represented: hospitals, family homes and community houses. The results showed a remarkable consistency in carers' assessments of the severity of management problem posed to them. An association was found between the reported frequency of occurrence and the assessment of the severity of behaviours, with certain behaviours likely to be rated as severe regardless of the frequency with which they occurred. Differences between residential settings were found, with carers in family homes and community houses rating more behaviours as presenting severe management problems than carers in hospital. The results from this study and other studies which have examined the relative severity of different behaviour topographies are discussed. PMID- 7787383 TI - Menopause in women with learning disabilities. AB - A brief questionnaire concerning previous and current menstrual status was sent to 280 women over the age of 35 on the Wandsworth Register for People with Learning Disabilities: 196 questionnaires (70.4%) were returned. One hundred and seventy-one were used in the analyses; 45 were from women with Down's syndrome. The results suggested that, compared with data on normal women, menopause may occur earlier in women with learning disabilities and earlier still in women with Down's syndrome. PMID- 7787382 TI - Electrophysiological correlates of psychopathology in individuals with mental retardation and epilepsy. AB - One hundred adults with mental retardation and epilepsy were randomly selected from hospital and community settings for a detailed study of psychopathology (maladaptive behaviour, psychiatric illness and personality disorder). All of them had a recording of interictal EEG within the 12-month study period. Of all the EEG recordings, nine were completely normal, 48 showed excessive slow background wave, and a further 43 showed epileptiform discharges. Of the 43 with epileptiform discharges in the EEG, 12 showed bilateral, diffuse, generalized activities (including 3 Hz abnormality), 18 showed temporal lobe focus (five left sided, four right-sided and nine bilateral), and the other 13 showed secondary generalization from a temporal lobe focus. A comparison of psychopathology between the groups with a generalized epileptiform activity in the EEG (n = 12) and focal changes (n = 18) did not reveal any significant differences. PMID- 7787384 TI - Autism in immigrants: children born in Sweden to mothers born in Uganda. AB - Three boys diagnosed as suffering from autistic disorder were born in Sweden to mothers born in Uganda. Two were related but the third boy was unrelated to the others. The prevalence for autistic disorder in Goteborg children born to mothers who were born in Uganda was 15% which is almost 200 times higher than in the general population of children. The possible reason for the high autism rate in this particular ethnic subgroup is discussed. PMID- 7787386 TI - International colloquium on mental retardation and Alzheimer's disease. PMID- 7787387 TI - Alterations in replication timing of X-chromosome bands in Rett syndrome. AB - A cytogenetic study has been carried out on 30 girls affected with Rett syndrome, 35 of their family members and 25 unrelated healthy control females. Karyotyping at the 850 band level revealed no detectable chromosome abnormalities in either the affected girls or their families. Observations on the sequence of the appearance of early replicating bands on both the active and the inactive X chromosome demonstrated the same replication patterns in all of the groups investigated with the exception that band Xp21 appeared with greater frequency in the Rett syndrome cells. A degree of variation was detected both between and within the subjects when the timing of the latest bands to replicate was investigated for the active X, but the same consensus order was obtained for all groups. A comparable number of elongated X-chromosomes was found in the girls with Rett syndrome (8%) when compared to their mothers (12%) when synchronized cells were treated with a short pulse of BrdU. If a disturbance in X-inactivation does contribute to the aetiology of Rett syndrome, it is at a level which is not detected by observations on the relative timing of replication of chromosome bands. PMID- 7787385 TI - Urine fetish in a man with learning disabilities. AB - Urine fetishes are uncommon. A 30-year-old man with learning disabilities and a fetish for observing women urinate is described, and the possible dynamic aspects of his paraphilia are discussed. PMID- 7787389 TI - [Effects of shi-ka-ron and Chinese herbs in mice treated with anti-tumor agent mitomycin C]. AB - The Shi-ka-Ron, and its constituent Chinese herbs Lithospermum erythrorhizon, Astragalus membranaceus and Ligusticum Wallichii were administered with antitumor agent, mitomycin C (MMC) to ICR mice, and their effects on murine macrophages and lymphocytes were studied. Peritoneal macrophages were significantly inhibited both in their number and chemotactic activity by MMC treatment. Splenic weight and blastogenic responsiveness to Concanavalin A of spleen lymphocytes also decreased significantly in MMC-treated mice. NK cell activity was also suppressed by MMC treatment. When these mice were orally treated with extracts of Shi-ka-ron or each Chinese herbs mentioned above, it showed protective effects to immunosuppressive mice on all 5 items studied. The number of macrophages, and the functions of macrophages and lymphocytes maintained the same or more than normal levels in MMC plus each group of these extracts treated mice. These results suggest that the Shi-Ka-Ron and Chinese herbs could resist immunosuppression induced by antitumor agent MMC, and its mechanisms might be correlated with stimulation of the RES (reticuloendothelial system), activation of T cell blastogenesis and NK cell cytotoxicity. PMID- 7787388 TI - Behaviour problems in Angelman syndrome. AB - Angelman syndrome (AS) is a genetic disorder that is associated with a deletion on chromosome 15, and is characterized by abnormalities or impairments in neurological, motor and intellectual functioning. While behaviour problems have been reported in clients with AS, relatively little is known about their developmental course and outcome. In this study, data on the nature and prevalence of behaviour problems among clients with AS were gathered from two sources: (1) a review of published case reports; and (2) parent responses to a survey of behaviour problems in a small (n = 11) sample of children with AS. Data from both sources showed that behaviour problems were present in males and females of all ages, and included language deficits, excessive laughter, hyperactivity, short attention span, problems with eating and sleeping, aggression, noncompliance, mouthing of objects, tantrums, and repetitive and stereotyped behaviour. Identification and treatment of severe behaviour problems in clients with AS may improve their adaptive functioning. PMID- 7787390 TI - [Progress in the study in treating senile dementia with traditional Chinese medicine]. PMID- 7787391 TI - [Progress in the prevention and treatment of ischemic cerebrovascular diseases with garlic extract]. PMID- 7787393 TI - [Study on effect of mediation principle in retarding progression of chronic renal failure]. AB - 100 Patients with chronic renal failure(CRF) were treated mainly by the mediation principle (MP). Results showed that the progression of CRF with MP was slower than that without MP. There was very significant difference (P < 0.01) between the regression coefficient. In addition, the effect of MP on the factors in promoting the progression of CRF, e.g., hypertension, albuminuria, hyperlipemia and immune function etc. was discussed in detail. PMID- 7787394 TI - [Clinical observation on treatment of myelodysplastic syndromes with yisuikang]. AB - 20 cases of myelodysplastic syndrome (MDS) patients were treated with Yisuikang (YSK) including MDS-RA 17 cases, MDS-RAEB 2 cases, MDS-RAEB-T 1 case. 14 patients were treated with YSK only, 6 cases were treated with both YSK and Western medicine. The result showed that 4 cases were remitted, 5 cases markedly improved, 6 cases improved and 5 cases ineffective, the total effective rate was 75.0%. It was found that YSK was effective in the treatment of MDS-RA or Qi-Blood Deficiency and Yu-Re Syndrome in TCM, while any other types were ineffective. They also found that types of TCM might be correlated with MDS. PMID- 7787395 TI - [Clinical observation on the treatment of ischemic heart disease with Astragalus membranaceus]. AB - 92 patients suffering from ischemic heart disease was successfully treated with Astragalus membranaceus (AM). The effect of the treatment was compared with that of Nifedipine and Tab. Salviae miltiorrhizae. The clinical practice showed that the group treated with AM yielded better results. After having administered the drug, the patients were markedly relieved from angina pectoris (heart stroke). Meanwhile the improvement of clinical objective index such as electrocardiogram (EKG) and impedance cardiogram can also be observed. The effective rate of EKG improvement was 82.6%. The treatment of ischemic heart disease with AM was significantly more effective in comparing with control group (P < 0.05). PMID- 7787392 TI - [Preliminary study on pathophysiology of liver-qi deficiency syndrome]. AB - The authors advocate a program for diagnosing Liver-Qi Deficiency Syndrome (LQDS) based on the TCM theory and clinical practice. Through investigation, LQDS was found to be widely existed as latent period or as external manifestation, which occupied 18.85% in Qi Deficiency Syndrome. The subjects were divided into four groups including normal group, Spleen-Qi Deficiency Syndrome (SQDS) group, LQDS with Liver diseases (LD) and LQDS with non-Liver diseases (NLD) group. In order to explore the essence, the simultaneous determinations were done on lactate dehydrogenase (LDH) and its isoenzyme, dopamine beta-hydroxylase (D beta H), trace element Zn and Cu, and other serological indexes such as GPT, TP, Alb, A/G, etc. The results were, the content of LDH and trace element Zn in both LQDS-NLD and SQDS were significantly lower than that of normal group. D beta H reflecting sympathetic nerve function in LQDS-NLD was significantly higher than that of both normal and SQDS group; comparing LQDS-LD and LQDS-NLD group, the content of GPT, LDH, LDH5 and trace element Cu in former was significantly higher than that of the latter, but the content of TP, Alb, A/G, D beta H and Zn in former was remarkably lower than that of the latter. In order to avoid confusion, in studying this syndrome, one should distinguish LD and NLD. PMID- 7787396 TI - [Study of relationship between TCM syndrome-types of malignant tumours and thyroid functional test]. AB - The relationship between the thyroid functional test in 107 malignant tumour patients' sera with Deficiency-Excessiveness Syndromes in TCM, was studied. The results revealed that there were significant differences between the FT3, FT4 in tumour and control groups (P < 0.01) as well as between the rT3, FT3/rT3 in each type of tumour and control groups (P < 0.05-0.01). There was also definite relationship between the FT3, rT3, FT3/rT3 and the degree of differentiation, rate of progression and malignancy of tumours as well. rT3 elevated and FT3 reduced in accordance with the lowering of body resistance and reinforcing of pathogenic factors. FT3, rT3, FT3/rT3 are essential factors that reflecting the wax and wane of body resistance in the cases with malignant tumours in modern medicine. PMID- 7787397 TI - [Study on objective parameters of syndrome differentiation of diabetic nephropathy]. AB - This is a study about objective parameters of Syndrome Differentiation of diabetic nephropathy (DN) using radio immunoassay (RIA) technique. The result showed that beta 2-microglobulin (beta 2-mG), alpha 1-microglobulin (alpha 1-mG) in blood rose significantly in both groups. The group of Spleen-Kidney Deficiency and Qi-Blood Deficiency as well as the group of Yang Deficiency caused edema and upward gush of turbid Yin, there was significant difference between two groups, also there was significant difference between the two groups in measuring on atrial natriuretic factor (ANP), pancreatic glucagon (PG) in blood and beta 2-mG. Immunoglobulin G (IgG), albumin (Alb), secretory immunoglobulin A(SIg A) in urine. So above-mentioned parameters offered us some objective data on Syndrome Differentiation of DN. It is vital in guiding the Syndrome Differentiation and treatment of DN. PMID- 7787399 TI - [Tube pregnancy treated with trichosanthin and followed up by hysterosalpingography]. AB - Twenty cases of unruptured tube pregnancy were treated with Trichosanthin intramuscularly given. Only two cases were eventually operated, so the effective rate was 90%. The hysterosalpingography was taken in 14 of 18 cases who was willing to accept the procedure at 0.5-1.5 year after the conservative treatment. Both tubes were patent in 10 of 14 cases, the rate of patency was 71.4%. PMID- 7787398 TI - [Effect of shenmai injection on sIL-2R NK and LAK cells in patients with advanced carcinoma]. AB - Serum interleukin-2 receptor (sIL-2R) level activities of natural killer cell (NK) and lymphokine activated killer cell (LAK) cells were determined in 60 patients with advanced carcinoma (AC) before and after treatment with Shenmai injection (SMI), 40 healthy persons were taken as non-carcinoma control (NC). The results showed that: Serum sIL-2R level in AC were much higher than those in NC (P < 0.05) and activities of NK and LAK cells in AC were much lower than those in NC (P < 0.05) before treatment. There was no significant difference among gastric cancer, colonic carcinoma and lung cancer (P < 0.05). After treatment with SMI we also found that the level of sIL-2R in all patients were obviously lower (P < 0.05) while the activity of NK and LAK cells were significantly higher than that prior treatment (P < 0.05). Linear correlation was not found between sIL-2R and NK, LAK cells. These data suggested that the immune function was compromised in AC. The mechanism of the inhibitory effect of SMI on carcinoma might be related to the activity of biological response modifier. PMID- 7787400 TI - [Effect of guzhen recipe on glucocorticoid receptor in senile rate thymocyte]. AB - The effects of Guzhen Recipe (GZ) which composed of Polygonum multiflorum, Cistanche deserticole, Rubus chiagii etc, on the number of thymocyte glucocorticoid receptor (GCR) sites, the GCR nuclear translocation rate, and the activity of serum thymic factors etc in senile rats were observed. The results showed: The number of thymocyte GCR sites, the contents of cytoplasmic protein, nuclear RNA and DNA, the thymus weight/body weight ratio and the serum thymic factors in senile rats were significantly decreased, while thymocyte GCR nuclear translocation rate increased obviously than that of young control rats. GZ, however, was capable of improving the above-mentioned changes of thymus in senile rats markedly, suggesting that GZ might weaken the inhibitory effect of glucocorticoid on the thymus by means of suppressing the translocation activity of GCR from cytoplasm to nucleus in senile rats, thus enhance thymus-dependent immune function in senile rats. PMID- 7787401 TI - [Comprehensive study on mechanism of leukocytogenic effect of fuzheng shengbai capsule]. AB - In order to study the mechanism of the therapeutic effect of Chinese medicine in raising white blood cells, the effects of multiplication of splenocyte of leukopenic mice, the activity of interleukin-2 (IL-2), the lipoperoxidant (LPO) content, the concentration of blood serum testosterone of male mice by using Fuzheng Shengbai Capsules (FZSBC) were observed. The results showed that the multiplication of splenocyte, the activity of IL-2, and testosterone level of the experimental group were significantly higher than those of the control group (P < 0.05-0.01), LPO was decreased slightly, which had no statistic significance. Therefore, the increasing of WBC had no relation with the content of LPO but was positively correlated with T lymphocytes as well as the activity of IL-2. This study showed that the mechanism of leukocytogenic effect of FZSBC might be that it was related with promoting the proliferation of T lymphocytes, elevating the activity of IL-2 and raising the testosterone level, but was not relevant with anti-LPO. PMID- 7787402 TI - [Study of treating experimental ulcerative colitis of spleen deficiency type with "guben yichang tablet" in guinea pigs]. AB - Guinea pigs were perfused with the extract of senna (20%). 3 days later glacial acetic acid (5%) was given intra-anally so as to replicate the animal model of Spleen Deficiency (SD) and ulcerative colitis which is the disease of Western medicine combined with the Syndrome in TCM. The model animals showed the symptoms of SD such as loose stool, anorexia, wasting, aversion of cold, laziness and loss of hair luster and the symptoms of ulcerative colitis such as abdominal distension and mucous bloody stool. The colonic lesion were observed by eyes that the mucosa were edematous, congestive with ulcerative foci. The pathological examinations showed edema and congestion in submucous layers; large amount of inflammatory cell infiltration; and the scaling and ulcer formation of epithelium mucosae. The above-mentioned symptoms and pathological changes were the same as SD and ulcerative colitis in clinical practice. The new medicine "Guben Yichang Tablet" against ulcerative colitis was given to guinea pigs for 7 days could abate their symptoms, increase their body weights and decrease the size of colonic ulcer and edema. PMID- 7787403 TI - Protein synthesis in specific tissues during sepsis. AB - BACKGROUND: The hypothesis that fractional protein synthesis rates (Ks) are tissue-specific and bidirectional during sepsis was tested in an animal model. MATERIAL AND METHODS: Ks in liver, triceps muscle, and diaphragm were measured in septic (n = 27) and control rats (n = 26). Sepsis was induced by a reproducible model established in our laboratory (intraperitoneal injection of sterile NaOH 0.75 N at 0.075 ml/100 g of body weight). Ks were measured using the flooding dose method in tissue obtained from the diaphragm, liver, and from the triceps muscle. RESULTS: In hepatic and diaphragmatic tissue, Ks were significantly higher in the septic animals (Ks: 112.2 +/- 8 and 5.4 +/- 1.9, respectively) than in control animals (Ks: 78.5 +/- 13 and 2.9 +/- 1.7, respectively). In the triceps, Ks were significantly lower in septic animals (Ks: 2.9 +/- 1.4) than in control animals (Ks: 5 +/- 1.8). CONCLUSION: The results suggest that in septic animals the rate of protein synthesis is enhanced in tissues of priority, such as the liver, and varies in response to differences in muscle activity. PMID- 7787404 TI - [Immunosuppressive effect of parenteral fat emulsions in defined immunostimulation]. AB - BACKGROUND: In the heterotopic rat heart allotransplant model we have previously shown that intravenous fat emulsions are to a various extent immunosuppressive or immunoneutral, dependent on their n-3/n-6 fatty acid ratio. Safflower oil (n-3: n 6 = 1:370), fish oil (7.6:1) and soybean oil (1:6.5) prolonged the transplant survival time to 13.3, 12.3 and 10.4 days compared to 6.7 days (oil control group; 1.2.1) and 7.8 days (saline control group) (p < 0.01), respectively. This study presents a correlation of graft survival to immunohistological, cell biological and biochemical parameters. MATERIALS AND METHODS: 20% emulsions of safflower oil, fish oil, soybean oil and a 1:1 mixture of safflower and fish oil (oil control group) were continuously infused (9 g fat/kg body weight/day; n = 10 each group) after transplantation. Subpopulations of infiltrating and circulating immunocompetent cells and leukotriene B4 and B5 release of circulating mononuclear cells were analyzed (on the 4th postoperative day). RESULTS: In the 2 groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 40% and the peripheral blood mononuclear cell interleukin-6 release by up to 45%. Beyond that, circulating T cells were reduced in the fish oil group. Leukotriene B4 was released in all groups to the same extent, leukotriene B5 exclusively in the fish oil group. CONCLUSIONS: Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration and mobilisation of immunocompetent cells. Soybean oil with a more balanced n-3/n 6 fatty acid ratio than safflower oil is significantly less immunosuppressive than safflower oil, and fat emulsions with a n-3/n-6 fatty acid ratio of 1:2 are immunologically neutral. PMID- 7787405 TI - [Suitability of monoclonal test sera for determination of blood group markers in positive direct Coombs test]. AB - BACKGROUND: Monoclonal reagents of the IgM type allow to test some red blood cell antigens (K; Jka; Jkb) by the tube centrifugation method at room temperature, for the examination of which the indirect antiglobulin test was necessary in the past. This permits to test antigens also when the direct antiglobulin test is positive, provided the sera do not contain too much supplement. MATERIALS AND METHODS: We tested a choice of monoclonal reagents of different manufacturers (for the ABO system, A subgroups, the Rhesus, MN, Kell, Kidd and Lewis system) for their ability to examine antibody-coated erythrocytes. To recognize false positive reactions of the reagents, erythrocytes without the particular antigen were coated with an incomplete antibody, and then the reagent was tested with these self-made Coombs control cells. RESULTS: We found no false-positive reactions for all tested anti-A, anti-B, anti-AB, and anti-A1 reagents. Some anti C, anti-c, anti-E, anti-e and anti-N reagents showed weak false-positive reactions, some anti-H, anti-D, anti-K, anti-Jka, anti-Jkb, anti-Lea, anti-Leb and anti-M reagents stronger false-positive reactions. PMID- 7787406 TI - The F-cell ratio: a clinically important parameter or just fine tuning? PMID- 7787407 TI - GIK in cardiac surgery. PMID- 7787408 TI - Amino acid-enriched glucose-insulin-potassium infusion improves hemodynamic function after coronary bypass surgery. A double-blind study in patients with unstable angina and/or compromised left ventricular function. AB - OBJECTIVE: The goal of this study was to assess the effects of a combination of glucose-insulin-potassium (GIK) and the amino acids aspartate and glutamate upon perioperative hemodynamics in coronary surgery patients with unstable angina and/or compromised left ventricular function. DESIGN: Prospective, randomized, and double-blind clinical study. SETTING: Operating theatre and intensive care unit (ICU) of a university hospital. PATIENTS: 44 coronary artery bypass graft (CABG) patients with unstable angina and/or compromised left ventricular function. INTERVENTIONS: 22 patients (group A) were given 1l of an infusion with 250g glucose, 100 I.U. fast-acting human insulin, 72 mmol potassium, 32 mmol magnesium, 20 mmol phosphate, 65 mmol aspartate, and 65 mmol glutamate, while another 22 patients (group C) were given 1l of an infusion with 50 g glucose, 72 mmol potassium, 32 mmol magnesium, and 8 mmol phosphate. The infusion rate was 1.2 ml/kg/h from the anesthesia induction onward to the commencement of cardiopulmonary bypass, when it was reduced to 0.8 ml/kg/h. When 11 had been infused, but not later than 4 a.m., the infusion was continued by giving 10% glucose at the same rate to both groups. Additional insulin (median: 14.2 I.U., range: 0-41.5) or saline was given during bypass to the A and C patients, respectively. A blood cardioplegia technique containing aspartate and glutamate was used in both groups. RESULTS: At aortic cannulation, the cardiac index (CI) had increased from the pre-anesthetic level by 15.3% (mean) (SD: 31.7%) in group A and decreased by 7.7% (15.1%) in C patients, p = 0.0069. Also the changes in stroke index (SI; p = 0.022), left (LVSWI; p = 0.0037) and right ventricular stroke work index (RVSWI; p = 0.0097) were more favorable in group A. Despite longer aortic cross-clamp, p = 0.031, and perfusion times, p = 0.042, in A patients, the change in cardiac index was also better in this group after bypass: At decannulation, the difference between mean values was 31.8%, p = 0.0001, and at arrival in the ICU it was 16.1%, p = 0.028. The same was also seen 8 h postoperatively and on the 1st and 2nd postoperative mornings; p = 0.034, 0.040, and 0.037, respectively (Wilcoxon test). Favorable changes were seen for the A patients also regarding SI at decannulation (p = 0.0002) and after 8 h (p = 0.017); LVSWI at decannulation (p = 0.0002), at arrival in the ICU (p = 0.0023), and after 8 h (p = 0.0011); and RVSWI at decannulation (p = 0.0027), at the ICU (p = 0.021), after 8 h (p = 0.014), and on the 1st postoperative morning (p = 0.039). However, the response to a hemodynamic loading test (6% hydroxyethyl starch 5 ml/kg) was similar in the 2 groups, and there was no difference in the need for inotropic support. CONCLUSIONS: Amino acid-enriched GIK infusion improves hemodynamic function in CABG patients with unstable angina and/or compromised left ventricular function. PMID- 7787409 TI - Is the transfusion requirement predictable in critically ill patients after admission to the intensive care unit? AB - OBJECTIVE: In intensive care medicine the clinical decision to order and transfuse red blood cells (RBC) is usually based on hematocrit or hemoglobin levels. The intention of this study was to investigate whether clinical or laboratory variables, taken after the admission of patients to the intensive care unit (ICU), are able to predict the transfusion requirement of the following 72 h. DESIGN: The values of initially measured systolic blood pressure, hematocrit level, and the values of 2 scores of severity of disease (Acute Physiology And Chronic Health Evaluation [APACHE-II], Mortality Prediction Model [MPM]) were calculated after the admission of patients to the ICU. The decision for transfusion was based on specific criteria. The median values of the scores, those of the variables, and the median number of transfused RBC units of the surviving group were compared to the values of the group of patients who died during hospital stay. The quantity of RBC transfusions was compared to the variables and score values by linear regression analysis. Additionally, the values of the patients who did not receive blood transfusion were compared to those of patients who required RBC. Furthermore, the patient group with neurosurgical diseases was compared to the group without neurosurgical diseases. PATIENTS: 117 patients were prospectively and consecutively investigated in an 8 bed ICU of a university hospital. RESULTS: Nonsurvivors required significantly more units of RBC during the first 72 h (p < 0.05). Patients who did not require transfusion had a higher hematocrit and a lower APACHE-II value at admission (p < 0.001). In the MPM values no differences were found. Patients with neurosurgical diseases had a higher initial hematocrit value, and they required less units of RBC in comparison to patients without neurosurgical diseases. In the analysis of linear regression neither in the initially measured systolic blood pressure nor in the APACHE-II and MPM we found a strong linear correlation to the quantity of blood transfusion. CONCLUSIONS: A hematocrit value < or = 20% and a APACHE-II score > or = 20 at the time of admission to the ICU referred to a demand for blood transfusion. We believe that these parameters are useful as predictive instruments. The initially measured systolic blood pressure had no prognostic capacity. In the individual patient a number of factors should be taken into account to decide whether to transfuse or not. PMID- 7787410 TI - Long-term evaluation of a continuous intra-arterial blood gas monitoring system in patients with severe respiratory failure. AB - OBJECTIVE: The purpose of this study was to evaluate the reliability and accuracy of a new continuous intra-arterial blood gas monitoring system (IABG; PB3300, Puritan Bennett) over a prolonged period of time (> 7 days). DESIGN: Prospective criterion standard study. SETTING: Anesthesiological intensive care unit in a university hospital. PATIENTS: 11 sensors were tested in 10 mechanically ventilated patients with severe respiratory failure. INTERVENTIONS: PO2, PCO2, and pH measured using IABG were compared to values obtained from 2 conventional blood gas analyzers. The quality of blood pressure tracings was assessed using a scoring system consisting of 5 grades. RESULTS: The median study period was 205h/sensor (range: 169-506h). 320 blood samples were obtained. The ranges of measured parameters were: PO2 = 46-433 mmHg, PCO2 = 25-79 mmHg, pH = 7.25-7.55. The mean (SD) differences for the whole study period were: -4.3 (11.9) mmHg for PO2, for the clinically important range (PO2 < 150 mmHg) -1.9 (5.4) mmHg, -2.8 (4.5) mmHg for PCO2, and -0.03 (0.04) for the pH value. The MD (SD) in relation to the sensor lifetime were for days 1-3: -1.1 (5.1) mmHg for PO2, -0.4 (3.9) mmHg for PCO2, and -0.01 (0.03) for the pH value; for days 4-6: -1.5 (6.0) mmHg for PO2, -3.3 (4.0) mmHg for PCO2, and -0.03 (0.03) for the pH value; for days 7 9: -2.5 (4.7) mmHg for PO2, -5.1 (4.6) mmHg for PCO2, and -0.04 (0.04) for the pH value; for days > 9: -4.9 (4.4) mmHg for PO2, -5.3 (4.1) mmHg for PCO2, and -0.05 (0.03) for the pH value. CONCLUSIONS: The IABG reliably measured blood gases and pH values with acceptable clinical performance based on the overall results. There was, however, a decline in the agreement of the sensors and conventional values with increasing sensor lifetime. The mean differences (bias) and the standard deviation of differences (precision) of PO2, PCO2 and the pH values were acceptable for clinical purposes up to day 6. The arterial blood pressure tracings and blood withdrawal were not adversely affected. No side effects due to the sensors occurred. In summary, a prolonged sensor use for a period of up to 6 days appears to be reasonable. This system offers on-line information on oxygenation, ventilation, and acid-base status and allows immediate detection of acute and potentially life-threatening events. PMID- 7787413 TI - Transcriptional activity of domain A of the rat glucagon G3 element conferred by an islet-specific nuclear protein that also binds to similar pancreatic islet cell-specific enhancer sequences (PISCES). AB - A pancreatic islet cell-specific enhancer element in the rat glucagon gene, Glu G3, contains two domains, one of which, domain A, has been shown to be necessary for Glu-G3 activity. In the present study, the functions of the isolated domain A of Glu-G3 were investigated by using transient reporter fusion gene expression and DNA binding assays. A single copy of domain A was transcriptionally inactive in glucagon-producing islet cell lines, whereas it did confer activity when combined with domain B, suggesting that Glu-G3 may be a bipartite element. Multiple copies of domain A did function independently as transcriptional enhancer in phenotypically distinct islet cell lines but not in several nonislet cell lines. Sequences (PISCES, pancreatic islet cell-specific enhancer sequences), similar to that of domain A of Glu-G3 and present in cell-specific control elements of the rat insulin I (Ins-E1) and rat somatostatin genes (SMS UE), are shown to be required for transcriptional activity of these elements. In addition, a protein was detected in islet cell lines that bound to the PISCES motifs within Glu-G3, Ins-E1, and SMS-UE. These results support the view that cell-specific control elements of the glucagon, insulin, and somatostatin genes share a functional regulatory sequence, PISCES, and provide direct evidence for the existence of an islet-specific, PISCES-binding transcription factor or closely related proteins being involved in the coordinate expression of islet hormone genes. PMID- 7787412 TI - Overexpression of the E2F-1 transcription factor gene mediates cell transformation. AB - The E2F transcription factor can regulate expression of numerous cellular genes controlling proliferation, including proto-oncogenes and genes regulating cell cycle progression. Therefore, genes comprising the E2F gene family could potentially contribute to carcinogenesis. To test the potential of E2F to act as a transforming gene, a cDNA encoding E2F-1 was constitutively overexpressed in established rodent cells using a retroviral vector. Overexpressed E2F-1 was functional, as shown by stimulation of a transfected adenovirus E2 promoter driving a chloramphenicol acetyltransferase reporter gene in E2F-1 overexpressing cells. This stimulation was dependent on functional E2F binding sites in the promoter. Examination of phenotype showed that E2F-1 overexpression mediated cell transformation as measured by the ability of cells to form colonies in soft agar medium. In addition, overexpressed E2F-1 shortened the duration of the G1 cell cycle phase in proliferating cells, a property characteristic of other transforming genes. These data provide direct evidence that E2F-1 can act as a transforming gene and a critical regulator of cell cycle progression and suggest the possibility of E2F involvement in carcinogenesis. PMID- 7787411 TI - Role of homeodomain protein binding region in the expression of Drosophila proliferating cell nuclear antigen gene: analysis with transgenic flies. AB - The regulatory region of Drosophila proliferating cell nuclear antigen (PCNA) gene consists of a promoter region (-168 to +24 with respect to the transcription initiation site) and an upstream region containing three homeodomain protein binding sites (HDB) (-357 to -165). The PCNA gene regulatory regions with HDB ( 607 to +137) or without HDB (-168 to +137) were fused with the lacZ and transgenic flies were established by P-element-mediated transformation. Male transgenic flies were crossed with wild-type females, and zygotic expression of the lacZ was monitored by quantitative beta-galactosidase assay, at various stages of development. Expression of the lacZ was high in embryos, first and second instar larvae, and adult females, and low at other stages of development. Only a marginal difference in expression was observed between flies carrying the homeodomain protein binding region and those not carrying it. Spatial pattern of the lacZ expression in the embryo visualized by immunostaining with the anti-lacZ antibody was similar to the distribution of the endogenous PCNA protein. Here, too, only a marginal difference was observed between transgenic flies carrying two different constructs of the PCNA lacZ. In genetic crossing experiments of transgenic flies with those carrying mutation in homeobox genes, no significant change in the lacZ expression pattern was observed. However, when male transgenic flies were crossed with female flies homozygous for a torso gain-of-function allele, repression of the lacZ expression was observed in the central region of the embryo. Because these local changes in the lacZ expression depend on the homeodomain protein binding region, unidentified homeodomain proteins are probably involved. Our results suggest that the promoter region is practically sufficient for expression of the PCNA gene and that the homeodomain protein binding region functions as a silencer when torso is activated ectopically. PMID- 7787415 TI - Transactivation by PPAR/RXR heterodimers in yeast is potentiated by exogenous fatty acid via a pathway requiring intact peroxisomes. AB - Peroxisome proliferator-activated receptors (PPARs) are orphan members of the nuclear hormone receptor superfamily. PPARs bind to cognate response elements through heterodimerization with retinoid X receptors (RXRs). Together PPAR/RXR regulate the transcription of genes for which products are involved in lipid homeostasis, cell growth, and differentiation. PPARs are activated by fatty acids and by nongenotoxic rodent hepatocarcinogens called peroxisome proliferators through as of yet undefined signal transduction pathways. In an effort to elucidate the requirements for PPAR function and the pathways of its activation, we expressed mouse PPAR alpha and human RXR alpha in the yeast Saccharomyces cerevisiae. Mouse PPAR alpha and human RXR alpha had little activity individually in yeast; however, when cosynthesized, they were able to synergistically activate transcription via cognate response elements. Transactivation was independent of exogenously added activators of either receptor but was potentiated by the addition of petroselinic acid, a fatty acid shown to activate PPARs in mammalian cells. Similar experiments were carried out in a mutant yeast strain lacking peroxisomes entirely or in a mutant strain deficient for 3-ketoacyl-CoA thiolase, the final enzyme of the peroxisomal beta-oxidation cascade. The findings showed that constitutive transactivation by PPAR/RXR did not require the complete beta oxidation pathway or intact peroxisomes but required intact peroxisomes for potentiation by exogenously added petroselinic acid. This study demonstrates that at least part of the mammalian peroxisome proliferator-signaling pathway can be faithfully reconstituted in yeast and that activation of PPAR by at least one particular fatty acid requires the integrity of peroxisomes. PMID- 7787414 TI - Lineage-specific alternative splicing of the human Fc gamma RIIA transmembrane exon requires sequences near the 3' splice site. AB - The human Fc gamma RIIA gene produces multiple transcripts, including those with (Fc gamma RIIa1) and without (Fc gamma RIIa2) the single exon encoding the transmembrane domain (TM). Previously, a fluorescence-based RT-PCR assay showed lineage-specific differences in Fc gamma RIIA transcript ratios (Fc gamma RIIa2/Fc gamma RIIa1). The mechanism of this lineage-specific expression was investigated in this study. Differential transcript stability does not play a major role, because transcript ratios remained constant in cells with both low (K562) and high (Dami) ratios following actinomycin D treatment. Transient expression studies in K562 and Dami cells using a minigene construct containing a 5.0 kb genomic fragment including the TM exon and adjacent intron and exon sequences showed recapitulation of endogenous transcript ratios. The TM exon was efficiently spliced in by the constitutive splicing machinery in HeLa cells, an Fc gamma RIIA-negative cell line. Lineage-specific TM exon skipping was markedly diminished by two independent minigene mutations: a point mutation of the first nucleotide of the TM exon, and a five basepair intronic deletion near a putative branchpoint. These data demonstrate that cis-acting sequences in or near the TM exon 3' splice acceptor site contribute to lineage-specific differences in Fc gamma RIIA transcript ratios. PMID- 7787417 TI - Overexpression, purification, and characterization of the ADP-ribosyltransferase (gpAlt) of bacteriophage T4: ADP-ribosylation of E. coli RNA polymerase modulates T4 "early" transcription. AB - The bacteriophage T4 Alt gene product is a component of the phage head and enters the host cell in the process of infection together with the phage DNA. It immediately ADP-ribosylates host RNA polymerase, presumably at only one of the two alpha-subunits. Transcription from T4 "early" promoters, therefore, might be catalyzed, at least in part, by an altered RNA polymerase. The T4 alt gene was cloned into the expression vector pBluescript. E. coli cells, transformed with this recombinant vector, overexpressed the 76 kDa Alt gene product, which was purified to homogeneity. The purified enzyme not only ADP-ribosylates the alpha subunit of RNA polymerase, but also subunits beta and beta', as well as the sigma 70-factor. The recombinant enzyme behaved like the native enzyme isolated from mature phage particles. The effect of the ribosylation reaction on the transcription activity of host RNA polymerase was investigated in vivo. It results in a modulation of T4 "early" promoter strengths, presumably, in a number of cases, leading to an overexpression of T4 "early" genes. The degree of overexpression, in some cases, should reach 50%, and seems to be well dosed for each promoter, controlling an individual transcription unit. PMID- 7787416 TI - Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells. AB - Translation of ribosomal protein (rp) mRNA is selectively repressed in mouse erythroleukemia (MEL) cells, which cease to proliferate upon differentiation, and in NIH 3T3 cells, for which growth is arrested by either serum starvation, contact inhibition, or treatment with the DNA polymerase inhibitor, aphidicolin. The efficiency of translation of rp mRNAs correlates with the expression of the gene encoding the cap binding protein, eIF-4E, as indicated by the fact that the abundance of the corresponding mRNA and protein also fluctuates in a growth dependent manner. To examine the hypothesis that eIF-4E plays a role in regulation of the translation efficiency of rp mRNAs, we utilized an NIH 3T3 derived eIF-4E-overexpressing cell line. These cells overproduce eIF-4E to the extent that even under conditions of growth arrest, the abundance of the respective protein in its active (phosphorylated) form is higher than that found in exponentially growing NIH 3T3 cells. Nevertheless, this surplus amount of eIF 4E does not prevent the translational repression of rp mRNAs when the growth of these cells is arrested by blocking DNA synthesis with aphidicolin or hydroxyurea. In complementary experiments we used an in vitro translation system to compare the competitive potential of mRNAs, containing the translational cis regulatory element (5' terminal oligopyrimidne tract) and mRNAs lacking such a motif, for the cap binding protein. Our results demonstrate that both types of mRNAs, regardless of their translational response to growth arrest, exhibit similar sensitivity to the cap analogue m7G(5')ppp(5')G. It appears, therefore, that the presence of the regulatory sequence at the 5' terminus of rp mRNAs does not lessen its competitive potential for the cap binding protein and that the growth-dependent decrease in the activity of eIF-4E does not play a key role in the repression of translation of rp mRNAs. PMID- 7787418 TI - An upstream activator sequence regulates the murine Pgk-1 promoter and binds multiple nuclear proteins. AB - The murine Pgk-1 gene is driven by a strong promoter that is regulated by a 304 bp upstream activator sequence (UAS). The activity of the UAS is high in undifferentiated embryonal carcinoma cells but declines when these cells are induced to differentiate with retinoic acid. The effect of the UAS on promoter activity is particularly striking when the activity of the Pgk-1 promoter is assayed following its integration into the genome, suggesting that it may function by regulating chromatin structure in the region of the core promoter. Three sites on the UAS bind nuclear proteins. Two of these sites bind factors present in both embryonal carcinoma cells and their differentiated derivatives whereas one site binds factors present only in differentiated cells. There appears to be both cooperation and antagonism in the binding of proteins to different sites in the UAS, suggesting that the activity of the Pgk-1 promoter is determined by the constellation of proteins assembled upstream of its transcription start site. PMID- 7787420 TI - Chemical shifts and three-dimensional protein structures. AB - During the past three years it has become possible to compute ab initio the 13C, 15N and 19F NMR chemical shifts of many sites in native proteins. Chemical shifts are beginning to become a useful supplement to more established methods of solution structure determination, and may find utility in solid-state analysis as well. From 13C NMR, information on phi, psi and chi torsions can be obtained, permitting both assignment verification, and structure refinement and prediction. For 15N, both torsional and hydrogen-bonding effects are important, while for 19F, chemical shifts are primarily indicators of the local charge field. Chemical shift calculations are still slow, but shielding hypersurfaces - the shift as a function of the dihedral angles that define the molecular conformation - are becoming accessible. Over the next few years, theoretical and computer hardware improvements will enable more routine use of chemical shifts in structural studies, including the study of metal-ligand interactions, the analysis of drug and substrate binding and catalysis, the study of folding/unfolding pathways, as well as the characterization of conformational substates. Rather than simply being a necessary prerequisite for multidimensional NMR, chemical shifts and chemical shift non-equivalence due to folding are now beginning to be useful for structural characterization. PMID- 7787419 TI - Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. AB - The nuclear receptor superfamily of transcription factors, which includes the retinoic acid receptors and v-erb A, play important roles in the molecular control of hematopoiesis. To identify nuclear receptors expressed in hematopoietic cells, we screened a human bone marrow cDNA library using a degenerate oligonucleotide and isolated a 1.85-kb full-length cDNA encoding a new human member of this superfamily, the peroxisome proliferator activated receptor gamma (hPPAR gamma). Two different hPPAR gamma transcripts were expressed in hematopoietic cells: a 1.85-kb transcript, which corresponds to the full-length mRNA (PPAR gamma 1), and a 0.65-kb transcript (PPAR gamma 2), which cannot encode all of the nuclear receptor functional domains. Normal neutrophils and peripheral blood lymphocytes, as well as circulating leukemic cells from patients with AML, ALL, and CML, express only PPAR gamma 2 on Northern blot analysis. In contrast, only the PPAR gamma 1 transcript was detected in a variety of human leukemia cell lines and in cultured normal primary bone marrow stromal cells. Both transcripts were detected in various fetal and adult nonhematopoietic tissues. We mapped the location of the hPPAR gamma gene to human chromosome 3p25 by somatic cell hybridization and linkage analysis. PPARs have been shown to be activated by peroxisome proliferating agents, long-chain fatty acids and arachidonic acid. Human PPAR gamma, although homologous to the PPAR gamma s of other species, has unique sequence and amino acid differences. Identification of hPPAR gamma will allow further understanding of its role in human cellular leukotriene, prostaglandin, and peroxide degradative or synthetic pathways, as well as its role in lipid metabolism and regulation of adipocyte differentiation. PMID- 7787421 TI - Internal motions of apo-neocarzinostatin as studied by 13C NMR methine relaxation at natural abundance. AB - Dynamics of the backbone and some side chains of apo-neocarzinostatin, a 10.7 kDa carrier protein, have been studied from 13C relaxation rates R1, R2 and steady state 13C-(1H) NOEs, measured at natural abundance. Relaxation data were obtained for 79 nonoverlapping C alpha resonances and for 11 threonine C beta single resonances. Except for three C alpha relaxation rates, all data were analysed from a simple two-parameter spectral density function using the model-free approach of Lipari and Szabo. The corresponding C-H fragments exhibit fast (tau e < 40 ps) restricted libration motions (S2 = 0.73 to 0.95). Global examination of the microdynamical parameters S2 and tau e along the amino acid sequence gives no immediate correlation with structural elements. However, different trends for the three loops involved in the binding site are revealed. The beta-ribbon comprising residues 37 to 47 is spatially restricted, with relatively large tau e values in its hairpin region. The other beta-ribbon (residues 72 to 87) and the large disordered loop ranging between residues 97-107 experience small-amplitude motions on a much faster (picosecond) time scale. The two N-terminal residues, Ala1 and Ala2, and the C-terminal residue Asn113, exhibit an additional slow motion on a subnanosecond time scale (400-500 ps). Similarly, the relaxation data for eight threonine side-chain C beta must be interpreted in terms of a three parameter spectral density function. They exhibit slower motions, on the nanosecond time scale (500-3000 ps). Three threonine (Thr65, Thr68, Thr81) side chains do not display a slow component, but an exchange contribution to the observed transverse relaxation rate R2 could no be excluded at these sites. The microdynamical parameter (S2, tau e and R2ex) or (S(slow)2, S(fast)2 and tauslow) were obtained from a straightforward solution of the equations describing the relaxation data. They were calculated assuming an overall isotropic rotational correlation time tau c for the protein of 5.7 ns, determined using standard procedures from R2/R1 ratios. However, it is shown that the product (1-S2) x tau e is nearly independent of tau c for residues not exhibiting slow motions on the nanosecond time scale. In addition, this parameter very closely follows the heteronuclear NOEs, which therefore could be good indices for local fast motions on the picosecond time scale. PMID- 7787422 TI - Theory and application of the maximum likelihood principle to NMR parameter estimation of multidimensional NMR data. AB - A general theory has been developed for the application of the maximum likelihood (ML) principle to the estimation of NMR parameters (frequency and amplitudes) from multidimensional time-domain NMR data. A computer program (ChiFit) has been written that carries out ML parameter estimation in the D-1 indirectly detected dimensions of a D-dimensional NMR data set. The performance of this algorithm has been tested with experimental three-dimensional (HNCO) and four-dimensional (HN(CO)-CAHA) data from a small protein labeled with 13C and 15N. These data sets, with different levels of digital resolution, were processed using ChiFit for ML analysis and employing conventional Fourier transform methods with prior extrapolation of the time-domain dimensions by linear prediction. Comparison of the results indicates that the ML approach provides superior frequency resolution compared to conventional methods, particularly under conditions of limited digital resolution in the time-domain input data, as is characteristic of D dimensional NMR data of biomolecules. Close correspondence is demonstrated between the results of analyzing multidimensional time-domain NMR data by Fourier transformation, Bayesian probability theory [Chylla, R.A. and Markley, J.L. (1993) J. Biomol. NMR, 3, 515-533], and the ML principle. PMID- 7787423 TI - Complete 1H, 13C and 15N NMR assignments and secondary structure of the 269 residue serine protease PB92 from Bacillus alcalophilus. AB - The 1H, 13C and 15N NMR resonances of serine protease PB92 have been assigned using 3D triple-resonance NMR techniques. With a molecular weight of 27 kDa (269 residues) this protein is one of the largest monomeric proteins assigned so far. The side-chain assignments were based mainly on 3D H(C)CH and 3D (H)CCH COSY and TOCSY experiments. The set of assignments encompasses all backbone carbonyl and CHn carbons, all amide (NH and NH2) nitrogens and 99.2% of the amide and CHn protons. The secondary structure and general topology appear to be identical to those found in the crystal structure of serine protease PB92 [Van der Laan et al. (1992) Protein Eng., 5, 405-411], as judged by chemical shift deviations from random coil values, NH exchange data and analysis of NOEs between backbone NH groups. PMID- 7787424 TI - High-resolution solution structure of siamycin II: novel amphipathic character of a 21-residue peptide that inhibits HIV fusion. AB - The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 A, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frechet, D. et al. (1994) Biochemistry, 33, 42-50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation. PMID- 7787426 TI - The American Thyroid Association: d'ou venons nous? Que sommes nous? Ou allons nous? (Whence do we come? What are we? Where are we going?). PMID- 7787425 TI - Three-dimensional structure of gurmarin, a sweet taste-suppressing polypeptide. AB - The solution structure of gurmarin was studied by two-dimensional proton NMR spectroscopy at 600 MHz. Gurmarin, a 35-amino acid residue polypeptide recently discovered in an Indian-originated tree Gymnema sylvestre, selectively suppresses the neural responses of rat to sweet taste stimuli. Sequence-specific resonance assignments were obtained for all backbone protons and for most of the side-chain protons. The three-dimensional solution structure was determined by simulated annealing calculations on the basis of 135 interproton distance constraints derived from NOEs, six distance constraints for three hydrogen bonds and 16 dihedral angle constraints derived from coupling constants. A total of 10 structures folded into a well-defined structure with a triple-stranded antiparallel beta-sheet. The average rmsd values between any two structures were 1.65 +/- 0.39 A for the backbone atoms (N, C alpha, C) and 2.95 +/- 0.27 A for all heavy atoms. The positions of the three disulfide bridges, which could not be determined chemically, were estimated to be Cys3-Cys18, Cys10-Cys23 and Cys17 Cys33 on the basis of the NMR distance constraints. This disulfide bridge pattern in gurmarin turned out to be analogous to that in omega-conotoxin and Momordica charantia trypsin inhibitor-II, and the topology of folding was the same as that in omega-conotoxin. PMID- 7787427 TI - Suppressive doses of thyroxine do not accelerate age-related bone loss in late postmenopausal women. AB - To examine whether suppressive doses of thyroxine have any adverse effects on bone, we evaluated various bone metabolic markers (lectin-precipitated alkaline phosphatase, osteocalcin, carboxyl-terminal region of type I collagen propeptide, tartrate-resistant alkaline phosphatase, and urinary excretion of hydroxyproline and pyridinium crosslinks), incidence of vertebral deformity, total body and regional (lumbar spine and radius) bone mineral densities (BMDs), and rates of bone loss in 24 late postmenopausal (more than 5 years after menopause) women who were treated with levothyroxine (L-T4) after total thyroidectomy for differentiated carcinoma. Depending on the clinical records, including serum TSH levels measured by immunoradiometric assay, these patients were divided into two groups. One group of patients was given suppressive doses of L-T4 (TSH < 0.1 mU/L, n = 12) and the other group was given nonsuppressive doses of L-T4 (TSH > 0.1 mU/L, n = 12). There was no difference in bone metabolic markers and incidence of vertebral deformity between the groups. In patients with TSH suppression, Z-scores of BMDs calculated from age-matched healthy women (n = 179, aged 55 to 80) were nearly in the zero range of values (0.077 at total body, 0.228 at lumbar spine, and -0.117 at trabecular region of lumbar spine). The rate of bone loss in TSH-suppressed patients (-0.849 +/- 0.605%/year) was not significantly different from that of nonsuppressed patients (-0.669 +/- 0.659). These prospective and cross-sectional data suggest that long-term levothyroxine therapy using suppressive doses has no significant adverse effects on bone. PMID- 7787429 TI - Role of neck ultrasonography in the follow-up of patients operated on for thyroid cancer. AB - The aim of the study was to evaluate the role of neck ultrasonography in follow up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level. PMID- 7787428 TI - Effects of suppressive doses of levothyroxine treatment on sex-hormone-binding globulin and bone metabolism. AB - The adverse effects of suppressive thyroxine treatment have previously been investigated and conflicting results have been published. This study aimed at evaluating the effects of subclinical hyperthyroidism on the liver and bones. We investigated the action of thyroxine on the liver by measuring sex-hormone binding globulin (SHBG) levels and on bone turnover by evaluating osteocalcin (BGP) in both pre- and postmenopausal women. We compared the levels of both proteins to those of untreated subjects matched for age, menopausal status, and weight. Bone mineral density (BMD) was evaluated by biphotonic absorptiometry only in postmenopausal women with estrogen replacement therapy (ERT) and compared to two postmenopausal estrogen-treated controls. Forty-five women with multinodular goiter (38) or postsurgical thyroid carcinoma (7) were studied. They had received LT4 for 3 to 5 years (150 +/- 34 micrograms/day for nontoxic multinodular goiter, 184 +/- 46 micrograms/day for thyroid carcinoma). All patients had normal free T3 concentrations. No significant difference was found in SHBG values between patients and controls whatever the menopausal status and the BMI; a significant increase in BGP was noted in premenopausal women (9.6 +/- 2.2 vs 6.7 +/- 2.3 ng/ml; p < 0.0006). No significant BGP and BMD variations were observed in treated postmenopausal women. In summary, the study of carefully matched patients and controls revealed that thyroxine treatment has no effect on SHBG levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787430 TI - Thyroid abnormalities among children in the contaminated area related to the Chernobyl accident. AB - Gradual increases of various radiation-related diseases including thyroid cancer following the Chernobyl accident have been recently reported. We have carried out systematic thyroid surveys in school children aged 10-15 years in the highly contaminated area and compared the results with a similar survey in a nonaffected neighboring area as a control. Systematic examinations of the thyroid gland were performed in 888 schoolchildren (408 males and 480 females) in the districts of Chechelsk city with 5 to over 40 Ci/km2 of radiation level for 137Cs. In the control area (Bobruisk city), 521 children with the same age range (229 males and 292 females) were examined. Thyroid surveys were carried out as follows: palpation, ultrasonography, blood examinations of thyroid function, and measurements of daily urinary excretion of iodine. Certain thyroid abnormalities were observed in the high radioactive fallout area more frequently than in the control region. In particular, the prevalence of multiple micronodular lesions in diffuse goiter in the contaminated area was significantly higher than in the control area. However, endemic goiter due to iodine deficiency was present in both districts. The environment factor of iodine deficiency might have resulted in the early occurrence of ultrasonographic thyroid abnormalities attributed to radioactive contamination. PMID- 7787432 TI - Different growth control of the two human thyroid cell lines of adenomatous goiter and papillary carcinoma. AB - To study the growth control of human thyroid cells in different stages of differentiation, we established two human thyroid cell lines of adenomatous goiter and papillary carcinoma. A 59-year-old female patient with adenomatous goiter was operated in September 1991, and a 27-year-old female patient with papillary carcinoma in May 1990. The thyroid cell lines were established by successive passage without cellular or genetic manipulations such as fusing other cell lines or oncogenic viral infection. These cell lines, human adenomatous goiter cells (hAG) and human papillary thyroid carcinoma cells (hPTC), exhibited a flattened polygonal shape and proliferated as a monolayer in cell culture. The doubling time of the hAG cells was 60 h in Ham's F12 medium supplemented with 10% fetal bovine serum, and that of the hPTC cells, 18 h in the same medium. Both cell lines expressed mRNA for TSH receptor and secreted cAMP into the medium during incubation with thyrotropin (TSH) at concentrations as low as 0.01 mU/mL. The effects of activators of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (TK), and estradiol (E2) on proliferation of the hAG cells and the hPTC cells were assessed by measuring cellular DNA content in 24-well plates with diaminobenzoic acid. TSH stimulated proliferation of the hAG cells, but it inhibited proliferation of the hPTC cells. Since TSH activates two signaling pathways, the adenyl cyclase-PKA system and phospholipase C-PKC system, we tested effects of dibutylyl cAMP (dBC) and phorbol myristate 13-acetate (PMA), separately. dBC stimulated proliferation of the hAG cells, but it inhibited that of the hPTC cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787431 TI - Biphasic effects of thyrotropin on invasion and growth of papillary and follicular thyroid cancer in vitro. AB - The rationale for TSH suppression in the treatment of follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) is to inhibit tumor growth, prevent recurrent disease, and eventually prolong survival. We analyzed the effects of TSH on invasion and growth of 3 FTC cell lines from 1 patient (FTC133, primary; FTC236, lymph node; FTC238, lung metastasis) and 2 PTC cell lines (PTC-UC1, PTC UC3). Cell growth and invasion through an 8-micron pore polycarbonate membrane coated with Matrigel were measured using the MTT assay. The dose-response to TSH was biphasic, stimulating invasion and growth of FTC and PTC at low concentrations (0.1-10 mU/mL), and inhibiting them at high concentrations (100 mU/mL). Interestingly, the metastatic FTC cell lines had higher basal invasion, but were less responsive to TSH than the primary tumor. TSH (1 mU/mL) stimulated invasion of FTC133 by 21%, FTC236 by 8%, and FTC238 by 8% (p < 0.01). At 100 mU/mL, TSH inhibited invasion of FTC133 by 21%, compared to 11% in FTC236 and 12% in FTC238. Also, TSH dose-dependently influenced proliferation of follicular thyroid cancer cells. At low concentrations it stimulated growth of FTC133 (20%) and inhibited it at high concentrations (23%; p < 0.01). Again, the amplitude of TSH effects was significantly smaller in the cell lines from metastatic tumors. TSH affected invasion and growth of PTC-UC1 and PTC-UC3 also biphasically. These results show that TSH may act as a mitogenic and antimitogenic growth factor for invasion and proliferation of well-differentiated thyroid cancer cells in vitro. PMID- 7787433 TI - An association between acromegaly and thyroid carcinoma. AB - Acromegaly has been associated with goiter as well as with benign and malignant tumors. Three cases of thyroid carcinoma in patients with acromegaly had been reported in the literature. We previously reported two additional cases of thyroid carcinoma and now present a third from 100 patients with acromegaly, exceeding the expected prevalence. All three thyroid carcinomas were multifocal, suggesting a generalized promotion toward malignancy. These patients had elevated levels of growth hormone and somatomedin-C [insulin-like growth factor (IGF-1)] at the time of thyroid carcinoma diagnosis. We discuss the role of IGF-1 in both benign and malignant thyroid growth, including the presence of IGF-1 receptors on thyroid cells, stimulation of thyroid cell replication by IGF-1, and paracrine secretion of IGF-1 and its binding proteins by thyroid cells. We propose possible mechanisms for the development of thyroid carcinoma in patients with acromegaly and discuss implications for the physician treating patients with acromegaly. PMID- 7787434 TI - Expression of human thyrotropin receptor by recombinant adenovirus. AB - We developed a new system for expressing a functional human thyrotropin receptor in eukaryotic cells using replication-deficient recombinant human type 5 adenovirus. COS-7 cells infected with recombinant adenovirus encoding human thyrotropin receptor cDNA showed specific thyrotropin binding (Kd = 1.8 x 10(-9) M) and cAMP responses after stimulation by human thyrotropin. Cells infected with control virus encoding firefly luciferase cDNA did not show thyrotropin binding nor cAMP responses following incubation with thyrotropin. This system will be useful for analyzing T cell immunity to thyrotropin receptor in patients with Graves' disease by expressing human thyrotropin receptor in patients' antigen presenting cells. PMID- 7787436 TI - Human liver triiodothyronine sulfotransferase: copurification with phenol sulfotransferases. AB - To ascertain whether triiodothyronine (T3) sulfotransferase coeluted with the known phenol sulfotransferases (PSTs) during purification, human liver thermostable PST, thermolabile PST, and T3 sulfotransferase were assayed with p nitrophenol, dopamine, and T3, respectively. Thermostable PST eluted from an ion exchange column in two sequential peaks of activity (Peaks I and II), followed by a peak of thermolabile PST activity. There were three peaks of T3 sulfotransferase with thermostable PST: two within thermostable PST Peak I, and one peak of T3 sulfotransferase activity within thermostable PST Peak II. There was a minor peak of T3 sulfotransferase with thermolabile PST. Further purification of thermostable Peak I showed coelution of T3 sulfotransferase with thermostable PST during gel filtration and affinity chromatography. SDS-PAGE revealed a major protein band at 31 kDa. Dehydroepiandrosterone sulfotransferase comprised only 4% of the final activity. This report demonstrates coelution of T3 sulfotransferase with thermostable PST, shows a potential additional isozyme of T3 sulfotransferase, and points out the apparent minimal role of dehydroepiandrosterone sulfotransferase in T3 sulfation. The findings support the hypothesis that thermostable PST is the predominant human liver T3 sulfotransferase activity. PMID- 7787435 TI - A novel, nonradioactive in vivo bioassay of thyrotropin (TSH). AB - A new and simple in vivo bioassay suitable for routine testing of pituitary and recombinant TSH preparations was developed. Male Albino Swiss CF-1 mice were given T3 in their drinking water to suppress endogenous TSH. T3, 3.0 micrograms/mL, given to mice for a period of 4 days decreased plasma total T4 (TT4) level to less than 10% of the nonsuppressed (control) level. Various doses of exogenous pituitary and recombinant TSH preparations were injected intraperitoneally and blood samples were obtained from the orbital sinus 6 h later. The TT4 level, measured by radioimmunoassay, served as the assay end point. The assay required injection of approximately 3.0 micrograms of pituitary human TSH (phTSH), 1.0 microgram recombinant human TSH (rhTSH), 0.2 microgram bovine TSH (bTSH), and 0.1 microgram rat TSH (rTSH) to attain half-maximal response. The maximal level of TT4 after TSH stimulation was similar to that observed in normal, nonsuppressed mice. The procedure developed is relatively easy to perform, economical, and, unlike earlier TSH bioassays, does not require the use of radionuclides. This bioassay showed acceptable sensitivity and reliability in structure-function studies of pituitary TSH from different species as well as rhTSH. PMID- 7787438 TI - The action of methimazole and L-thyroxine in radioiodine therapy: a prospective study on the incidence of hypothyroidism. AB - Thiourea drugs have been postulated to possess radioprotective property. We studied the effect of adjunctive antithyroid drugs (ATD) and L-thyroxine (L-T4) on the result of radioiodine (RAI) 131I therapy and determined the incidence of hypothyroidism and relapse of hyperthyroidism. One hundred and fifty-nine patients with Graves' disease were randomized prospectively to receive either RAI alone or adjunctive ATD in a form of block-replacement regimen of methimazole (MMI) plus L-T4 for 6 months. The patients were observed for a mean period of 4.6 (range 2-10) years. The incidence of permanent hypothyroidism was studied and the effect of ATD on iodine kinetics was analyzed. The cumulative incidence of hypothyroidism in the ATD group was significantly lower than the RAI group (p = 0.0009), and the difference is accounted by a reduction of early hypothyroidism within 12 months from 20.2 to 3.7% (p = 0.003). The incidence of late hypothyroidism was similar between the two groups. Treatment with ATD did not affect the one dose cure rate with RAI (61.2 vs 55.5%, p = NS), but the time to achieve euthyroidism was significantly earlier with adjunctive ATD (2 vs 8 weeks, p < 0.02). The incidence of relapse within the first year after one dose was also similar between the two groups (38.7 vs 44.5%, p = NS). Comparing the kinetics of the therapeutic dose with a tracer dose, patients receiving MMI were found to be underdosed by 22% (p = 0.003) and the biological half-life was significantly shortened. We conclude that ATD rendered euthyroidism earlier without compromising the one dose cure rate of RAI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787439 TI - Patient treated solely with thyroid hormone. PMID- 7787437 TI - Expression of growth factors and growth factor receptors in normal and tumorous human thyroid tissues. AB - A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates with morphological alterations in proliferative lesions of thyroid, we examined the localization of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and their common receptor, EGF-receptor (EGF-R), insulin-like growth factor-1 (IGF 1), IGF-1-receptor (IGF-R) and IGF binding proteins (IGFBP)-1, -2, -3, and -4, nerve growth factor (NGF), and its receptor NGF-receptor (NGF-R), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF), in normal thyroid tissue and various thyroid tumors. We applied the streptavidin biotin technique to formalin-fixed, paraffin-embedded tissues. We studied 8-16 different cases of each of the following: normal human thyroid, multinodular hyperplasia, follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma. EGF, TGF-alpha, and their receptor EGF-R were widely expressed in normal thyroid and in all the thyroid lesions examined. IGF-1 and IGFBP-1 were diffusely present in all different thyroid tissues as well. There was no difference in staining intensity or distribution that correlated with the pathological process. IGFBP-4 seemed to have a variable expression. IGFBP-2 and -3 were detected only in medullary carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787441 TI - Paul Starr Lectureship. PMID- 7787440 TI - Sidney H. Ingbar Distinguished Lectureship. PMID- 7787442 TI - Van Meter Award. PMID- 7787443 TI - Distinguished Service Award. PMID- 7787444 TI - [Echographic morbidity due to Schistosoma haematobium in a peripheral district of Bamako in Mali, Missabougou]. AB - Frequency of urologic lesions was evaluated in 408 children from 6-15 years old in a suburban area of Bamako district in Mali, Missabougou; 65.2% from children were infected by Schistosoma haematobium, 13% by Schistosoma mansoni and 0.2% by Schistosoma intercalatum. Urologic lesions have been demonstrated in 223 cases among which 66 cases of urinary bladder lesions, 108 cases of hydronephrosis and 49 cases of mixed lesions. In order of the frequency we had the following uropathic lesions: wall thickening, wall irregularities, localised hypertrophies and hydronephrosis. We did not found any lesions in 185 children. Infection due to S. haematobium did not varied significantly in spite of age group, sex, schooling of children or the profession of the parents. Lesions were strongly correlated with age group (47.8 and 61.3% in 6-9 and 10-15 years old respectively) (p < 0.01) and with intensity of infection as measured by urinary egg counts (p = 0.0017). PMID- 7787446 TI - [Malaria and febrile pathology of expatriates in Brazzaville in 1993]. AB - Between January 1 and December 31, 1993, malaria was found in 22.6% of unexplained fever cases among expatriates in Brazzaville, i.e. 0.5% of all consulting physicians at the Medico-Social Centre of the Cooperation francaise. There are three possible explanations for the small proportion of paludism infection among expatriates: the low density of anopheles in the city centre, living conditions that restrict possible man-vector contacts and use of chemoprophylaxis. Considering the risks of self-treatment which are not insignificant, the authors on the importance of taking into account these facts when treating cases of fever among European residents in Brazzaville. PMID- 7787445 TI - [Variation of cholostase enzymes (5'-nucleotidase and alkaline phosphatase) during a specific treatment for malaria in the Gabonese child]. AB - Biological variations of 5'nucleotidase (5'NU) and alkaline phosphatase (AP) in 102 Gabonese children with malaria features (MF) and malaria infection (MI) receiving treatment are reported. [formula: see text] During the therapeutic assay, 5'NU rate decreases faster than AP'S; Fourteen days after the beginning of treatment, difference between AP MF and AP M1 is still significant. Enzymes decrease is an indication of the malaria drugs tolerance (MSP (*)). PMID- 7787447 TI - [Cerebral toxoplasmosis in a hospital environment in Lome (Togo)]. AB - The authors report the clinical, serological and neuroradiological results of a study about 23 cases of cerebral toxoplasmosis in the Teaching Hospital of Lome. Response to antitoxoplasmic treatment was rapidly favourable with all patients. Cerebral toxoplasmosis was the inaugural manifestation of AIDS in 20 of the 23 patients. PMID- 7787448 TI - [Study of an HIV positive, tropical origin population in a refugee center in France]. AB - The study describes HIV positive refugee patients, who were seen over a 3 years period at COMEDE, a dispensary for foreign nationals. COMEDE offered a HIV test to every patient, and it followed up on the disease and its prevention. Out of 5,234 tests, 328 were positive (6.3%). Less than 5% of the patients refused the test. All the patients returned for the result; 88.4% were African and 11.3% Haitian. The mean age was 31.5 years. The male/female sex ratio was 1.28. In this study, 94.5% of the HIV patients were HIV1, 3% HIV2 and 2.5% carried both strains; 78% were asymptomatic, 7% had ARC and 12.5% had AIDS. The prevalence of tuberculosis was high (10.6%), especially for AIDS patients (65%); Treponematosis prevalence was 13% and toxoplasmosis was 62.8%; 40% had intestinal parasites. 36.4% of the women became pregnant during the study; 41% of the pregnancies were terminated, while 27% went full term. The proportion of missing patients after 6 months was high (57%) because of numerous factors which prevented them from returning. This study shows the importance of proposing a HIV test to this immigrant population, although follow-up is difficult, due to social and economic factors. PMID- 7787449 TI - [Epidemiology of schistosomiasis in a suburban school area of Bamako (Republic of Mali)]. AB - Epidemiology of schistosomiasis has been assessed in October, 1990 in three primary schools of a suburban district of Bamako: Magnambougou. It was a cross sectional study which was carried out on an hazardous sample of 549 pupils of 7 to 14 years old. The Kato-Katz and urine filtration methods were used to search schistosome eggs. The prevalence rate was 50% (256/512) in Schistosoma haematobium and 5.6% (26/464) in S. mansoni. Children from 11-14 years old were more infected by Schistosoma haematobium (59.4%), than those from 7-10 years old (35.2%) (p < 0.005). Among these children, 26.2% excreted more than 100 eggs per 10 ml of urine. The infection did not varied significantly no matter what the sex is (53.7 and 44.8% respectively in boys and girls) (p = 0.05). According to the residence, pupils living in Magnambougou were more infected (54.9%) than those of others district (31.1%) (p < 0.001). Likewise, S. haematobium infection was more important in A and C schools (64.9 and 73.2% respectively) than in B school (11.2%) (p < 0.001). Two major snails species which are the intermediate hosts of urine schistosomiasis in Mali (Bulinus truncatus and Bulinus globosus) were found in the shelters: however, B. truncatus was only infected in 13.1% (19/145). Contamination was local and "ruralization" activities (particularly gardening) seemed to be the most important displaying factor. PMID- 7787450 TI - [Pathogenic approach of thrombopenia in dengue and its hemorrhagic complications]. AB - Dengue is a frequent viral infection in the intertropical countries. The frequency and the severe forms of this infection are a real problem of public health. The haemorrhagic forms of the disease are constantly associated with thrombocytopenia. Its pathophysiology is still unclear. Among the different hypothesis, immune mechanisms play the main role. The authors discussed here the responsibility of the binding of immune complexes and the role of cytokines. PMID- 7787451 TI - [Prevalence of urinary schistosomiasis in a school environment in N'Djamena (Chad)]. AB - A parasitologic investigation, realised between March and November 1993, among 532 pupils 6-15 years old living in N'Djamena's peripheric quarter and in 5 Chari Baguirmi's villages had showed urogenital schistosomiasis infection prevalence is 11.8%. PMID- 7787452 TI - [Trypanosomiasis from Trypanosoma brucei gambiense in the center of north-west Uganda. Evaluation of 5 years of control (1987-1991)]. AB - In Uganda, a case-finding and treatment programme has been implemented by Medecine Sans Frontieres (MSF) and the Ministry of Health in the North of West Nile province. Data collected in the hospital of Moyo from January 1987 to June 1991 were analyzed. Forty eight hundred and twenty two cases of trypanosomiasis due to T. B. gambiense has been recorded. Cumulative incidence rate for this period was 5.6%. Passive and active case-finding strategies were used, both based on Card Agglutination Test (CATT) as screening tool, followed by parasitological examinations. The mobile teams identified 1906 of the 4,822 cases (39.5%). Case fatality rate was 2.6%. This study confirmed the association between social and political disruptions, large movements of population and extension of trypanosomiasis. Active case-finding seems to quickly reduce disease prevalence in hyper-endemic areas. An integrated programme is then necessary to control sleeping sickness transmission. PMID- 7787453 TI - [Zoonotic cutaneous leishmaniasis to the north of Isfahan. Human infection in 1991]. AB - An epidemiological investigation was carried out in 1991 at four villages in Borkhar rural district, north of Isfahan, Iran, to obtain baseline data for studying the candidate vaccines of zoonotic cutaneous leishmaniasis (ZCL). A study of prevalence among 6,284 inhabitants showed a rate of 61.95% for scars and 2.9% for active lesions. The under 10 years old showed a rate of 42.9% for scars and 7.5% for active lesions. The above 10 years old showed a rate of 71.06% for scars and 0.7% for active lesions. The highest prevalence of the disease is in the seasons of autumn and winter. The incidence of the disease was 68.4 per thousand in 1991. Comparing the results of this study with those from the years 1963-1965 showed that the disease incidence has increased after 28 years and ZCL has remained as an important health problem in this area. PMID- 7787454 TI - [Prevalence of toxoplasmosis in a population of pregnant women in Antananarivo (Madagascar)]. AB - The prevalence of Toxoplasma antibodies by ELISA was studied in Antananarivo area, in the Republic of Madagascar, among a population of 599 pregnant women. The overall prevalence is 83.5%. From the age of 19 years old, 75% of the pregnant women have already antitoxoplasma antibodies. The ethnic factor, the foods habits or the presence of a domestic cat do not seem to have an influence on prevalence of toxoplasmosis among the studied population. PMID- 7787456 TI - [AIDS. Hypothesis on the origin and emergence of HIV]. AB - Cross-species transfer of simian immunodeficiency viruses (SIV) may occur accidentally. This transfer, with the possible exception of the virus of the sooty mangabey monkey, leads to a biological dead-end. Thus, only serial passages of the virus from man to man, through blood inoculation, could explain its progressive evolution from SIV to HIV. Such an artificial cycle may have been initiated, in the 1910s, following the introduction of syringes and needles into the region of the African Great Lakes, a region where some communities were considering that the inoculation of blood from certain individuals or from monkeys was a very powerful magical remedy. The first HIV-1 infection may have emerged in the 1940s, in one of these isolated communities among which the virus remained at first confined before spreading to other populations. PMID- 7787457 TI - [Risk of contamination by Borrelia burgdorferi S. lato in a forest environment. Survey during 13 months of abundance of the tick Ixodes ricinus and its level of infestation by the Lyme borreliosis agent in Brittany]. AB - The authors, in a forest in Brittany previously studied for several years, caught by flagging, each month from April 1992 to May 1993, nymphs of I. ricinus tick, and looked by indirect immunofluorescence, for B. burgdorferi infestation. An amount of 1,506 ticks was thus studied. Infestation frequency was varying from 0 per cent in January and February to 14.4 per cent in August. Standarding of tick collecting method allowed to establish, for each month, a tick, "availability" index, and, according to the spirochete infestation frequency, to do estimation of the risk level, for human visiting the concerned forest, of being infected by B. burgdorferi. Obtained results show that this risk is the highest in August, and quite non-existent in January and February. PMID- 7787455 TI - [Protein profile in malnutrition states of the Ivory Coast child]. AB - Prospectively assessment of nutritional status, besides anthropometric parameters measurements, included determination of the following plasma proteins: albumin, transferrin, retinol-binding protein and thyroxine-binding prealbumin, usually regarded as useful indices of protein depletion states. Patients' inflammatory or infectious diseases were investigated by measuring the two most reliable acute phase reactants (orosomucoid and c-reactive protein). This study was conducted on a group of 56 pediatric patients malnourished and 54 age- and sex-matched healthy subjects as controls. Data showed a higher prevalence of inflammatory process during the course of malnutrition as revealed progressive but severe alteration of the Prognostic Inflammatory and Nutritional Index (PINI) or CRP x a1-GPA/Alb x TBPA. On the other hand, kwashiorkor and marasmus seemed to be a precipitating cause of infectious or/and inflammatory process. We, therefore, conclude that the PINI scoring system should be for the pediatricians, a sensitive and precious tool allowing the correct follow-up of inflammatory pole in nutritional disorders in developing countries. PMID- 7787458 TI - [Extra-pulmonary tuberculosis and dissemination in patients infected by the human immunodeficiency virus in Bujumbura (Burundi)]. AB - Scattered and extra pulmonary tuberculosis patients coinfected with HIV represent in Bujumbura (Burundi) more than 56% of tuberculosis cases. The high prevalence of these forms could be explained partly by the hospital recruitment, therefore by patients already strongly immunocompromised. Performing further examinations as abdominal echography, ganglionic biopsy (or firstly a puncture sucking procedure) permit to reveal multifocal affections. These examinations provide valuable diagnostic arguments specially among the negative bacteriological forms. PMID- 7787459 TI - Embryology and congenital heart disease. PMID- 7787460 TI - "Acquired" left ventricular-to-right atrial shunt (Gerbode defect) after bacterial endocarditis. AB - We present, with echocardiographic and intraoperative findings, a rare case of left ventricular-to-right atrial communication (Gerbode defect) after endocarditis associated with Staphylococcus aureus. (Tex Heart Inst J 1995;22:100 2) PMID- 7787461 TI - Radiation-induced superior vena cava syndrome. AB - A 59-year-old man developed superior vena caval obstruction 20 years after receiving a radiation treatment for primary germinal cell tumor of the mediastinum. Venous decompression was achieved by anastomosing a 10-mm ringed polytetrafluoroethylene graft from the left internal jugular vein to the right atrium, which yielded immediate relief of symptoms. A left internal jugular venogram demonstrated graft patency 11 months post-operatively, and the patient remained free of symptoms of superior vena caval obstruction 29 months postoperatively. PMID- 7787462 TI - Successful stenting of a superior vena caval bypass graft. Report of a case. PMID- 7787463 TI - "Pseudocoarctation" of the aorta. PMID- 7787464 TI - Pentalogy of Cantrell vs pentalogy of Fallot. PMID- 7787465 TI - Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products. AB - Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium. PMID- 7787466 TI - Coronary angioscopy. AB - Coronary angioscopy will not replace angiography as the gold standard for imaging atherosclerotic coronary arteries. However, there may well be a clinical niche for a technology that gives accurate information regarding a specific lesion, if that information can be used to improve the acute or chronic outcome of an interventional procedure. Our experience demonstrates that angioscopy indeed provides this information. Using angioscopy, we now have access to information regarding arterial wall disease that heretofore has been available only at necropsy. In addition, whereas angiography has provided only a 2-dimensional, gray-scale image of the coronary vessels, angioscopy offers a full-color, 3 dimensional perspective of the intracoronary surface morphology. These important lesion-specific details, not reliably available from angiography alone, may ultimately be used to improve patient outcome and to assess risk. PMID- 7787467 TI - Recent advances in the treatment of acute myocardial infarction. AB - A number of recent major clinical trials have added substantially to the understanding of what the current "optimal" therapy for acute myocardial infarction may include. This review highlights a number of studies that have been published or presented within the last 2 years. Clearly, there is still room for improvement, but we have made considerable progress in recent years, and the pace of our advances continues to accelerate. PMID- 7787468 TI - Dobutamine echocardiography and myocardial contrast echocardiography. Two new techniques for the assessment of myocardial viability. AB - As investigators have discovered that cardiac regions displaying resting wall motion abnormalities are not the necessary equivalent of myocardial scar (and therefore of irreversible injury) but are potentially viable regions rendered dysfunctional by stunning or hibernation, a new field of medicine has developed to identify viable myocardium that can improve in function after revascularization. Moreover, improvements in myocardial preservation and perfusion during coronary artery bypass grafting and percutaneous transluminal coronary angioplasty have enabled patients with poor resting ejection fractions to undergo safer revascularization. In this review, we describe briefly the diagnostic techniques most commonly used in identifying dysfunctional but viable myocardium. We give specific attention to the assets and limitations of these techniques and special emphasis to 2 promising new techniques: dobutamine echocardiography and myocardial contrast echocardiography. PMID- 7787470 TI - Cardiac rehabilitation, exercise training, and preventive cardiology research at Ochsner Heart and Vascular Institute. AB - We review data from our institution demonstrating the benefits of cardiac rehabilitation and exercise training on coronary risk factors, exercise capacity, behavioral characteristics, and quality of life in various subgroups of patients. In addition, we discuss our research in several other areas of preventive cardiology, including lipid disorders, hypertension, left ventricular hypertrophy, fish oils, and antioxidants. We believe that we are now in a very exciting era in which a multifactorial approach to the primary and secondary prevention of coronary artery disease is needed in order to further reduce morbidity and mortality rates. PMID- 7787469 TI - Use of amiodarone in the postmyocardial infarction patient. AB - Amiodarone appears to be an effective antiarrhythmic agent for reducing mortality in the postmyocardial infarction patient with ventricular ectopic activity. Such activity has long been recognized to have an adverse effect on prognosis after acute myocardial infarction. When a strong correlation between ectopic activity and left ventricular dysfunction was demonstrated, ventricular ectopic activity was thought to be a consequence of underlying myocardial damage. However, ventricular ectopic activity is now considered to be an independent risk factor for mortality after myocardial infarction. Because of the basic premise that a positive correlation existed between arrhythmia suppression and improved survival, it had been common practice to use antiarrhythmic agents to treat asymptomatic ventricular ectopic activity in the postinfarction patient. After the results of the Cardiac Arrhythmia Suppression Trial (CAST) were released, this practice was largely abandoned. In the post-CAST era, however, amiodarone has appeared to improve survival in patients who have sustained myocardial infarctions. In this report, we briefly review the pharmacology of amiodarone and discuss the results of relevant clinical trials. Large, multicenter trials currently under way may clarify some of the unanswered questions surrounding the use of this promising antiarrhythmic agent in postmyocardial infarction patients. PMID- 7787472 TI - Effect of IgM-positive crossmatches on survival in heart transplant recipients. AB - To determine whether an IgM-positive crossmatch adversely affects the results of heart transplantation, we conducted a retrospective study of 125 orthotopic heart transplant recipients. A direct donor-recipient crossmatch was performed retrospectively on sera from all patients by the standard National Institutes of Health (NIH) method and the antihuman globulin (AHG) procedure. The patients were then divided into 3 groups as follows. Group 1 comprised 110 patients with a negative NIH and AHG crossmatch (control group). Group 2 comprised 5 patients with a positive NIH crossmatch and a negative AHG crossmatch. Group 3 comprised 10 patients with positive NIH and AHG crossmatches. All positive crossmatches in group 3 patients converted to negative after treatment of sera with dithioerythritol, indicating that the initial result was due to IgM antibodies. All patients received standard immunosuppressive treatment. An IgM-positive crossmatch did not affect the number or severity of rejection episodes among the 3 groups, nor did it have an effect on the incidence of infection. Whereas coronary artery disease was detected by angiography in 16 of 110 patients (14.6%) in group 1 and in 1 of 10 patients (10%) in group 3 (P = NS), no patient in group 2 was affected. Actuarial survival at 1 and 2 years post-transplant was significantly better for patients with an IgM-positive crossmatch (group 2) (100% survival at 2 years) than for patients with a negative crossmatch (group 1) (73% at 1 year and 71% at 2 years, P < 0.05). Based on our study, the effect of an IgM positive crossmatch on survival is difficult to interpret because of the small sample size. An IgM-positive crossmatch, however;did not appear to have a deleterious effect on survival. It may be that the IgM antibody has an immunoregulatory role. A larger series of patients with positive crossmatches and longer follow-up will be necessary to evaluate the importance of these results. PMID- 7787471 TI - Endomyocardial biopsy in the evaluation of conditions leading to cardiac transplantation and in the evaluation of cardiac allograft rejection. PMID- 7787473 TI - CardioVascular Care Providers. A pioneer in bundled services, shared risk, and single payment. AB - In 1984, physicians at the Texas Heart Institute developed CardioVascular Care Providers, Inc., the 1st packaged pricing plan for cardiovascular surgery. Under this arrangement, all services (including physician and hospital charges) are covered by a global payment package (bundled service). The resulting flat fee is lower than the sum of the individual charges. Since November 1984, the plan has been offered to the non-Medicare (< 65-year-old) population through contracts with self-insured corporations, prepaid health plans, union trusts, and foreign governments. In 1993, it was extended to Medicare patients who require coronary artery bypass grafting. Our experience has shown that the plan lowers costs, increases patient access, allows payers to forecast their expenses, and streamlines the billing process, while maintaining a high quality of care and enabling patients to choose their own providers. Our success with this approach is attributed not only to the plan's simplicity but also to the fact that it is physician-directed and organ-specific, involving many related specialties. Equally important keys to success include our hospital's large patient population and extensive database. Similar packaged pricing plans have been adopted by several other cardiovascular centers. The approach is now being evaluated by Medicare in 6 other hospitals nationwide. With time, this approach is likely to become an increasingly popular reimbursement option. PMID- 7787474 TI - The Medicare Participating Heart Bypass Demonstration Project in Houston, Texas. The experience of St. Luke's Episcopal Hospital, Texas Heart Institute, and CardioVascular Care Providers, Inc. AB - While passage of a health care bill remains uncertain, the structure of health care in the United States is nonetheless changing rapidly. In some cases, physicians and hospitals are working more closely with one another to provide high-quality care at lower costs. Patients, physicians, hospitals, and insurers (including the Federal government) can all benefit from such an arrangement. We review here the experience with a program of bundled-free (physician and hospital) cardiovascular care for Medicare patients at the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, Texas. PMID- 7787475 TI - Scopulariopsis endocarditis associated with Duran ring valvuloplasty. AB - Fungal endocarditis is rare and is usually caused by Aspergillus and Candida species. We present a patient with endocarditis caused by Scopulariopsis brevicaulis. The patient had a history of mitral valve disease and, 1 year earlier, had undergone valvuloplasty with the placement of a prosthetic Duran ring in the mitral valve position. S. brevicaulis was cultured from samples of a large vegetation on the mitral valve apparatus. The mitral valve was replaced with a St. Jude mechanical prosthesis. The patient was treated with amphotericin B but was later switched to oral itraconazole when antibiotic tests indicated susceptibility to that agent. We believe this is the 1st reported case of endocarditis caused by Scopulariopsis. PMID- 7787476 TI - The epidemiology of prosthetic heart valves in the United States. AB - The Center for Devices and Radiological Health of the Food and Drug Administration, in collaboration with the National Center for Health Statistics, conducted the Medical Device Implant Supplement to the 1988 National Health Interview Survey, generating the 1st available population-based estimates of the use of prosthetic heart valves in the United States. The 1988 National Health Interview Survey was a massive, nationally representative cross-sectional survey that encompassed 47,485 households and 122,310 individuals. Data from the Medical Device Implant Supplement indicate that an estimated 253,283 persons with 279,175 heart valves were present in the civilian, non-institutionalized US population (population prevalence of 1.1/1,000, 95% CI 0.8-1.3). Prevalence of valve prostheses ranged from 0.2 per 1,000 in those age 44 and under to 5.3 per 1,000 in those 75 years of age and older. Age-adjusted prevalence of valve prostheses did not differ significantly according to sex, race, region of residence, education, or income of recipients. Two thirds of aortic valve recipients identified by the survey were male, compared with only one third of mitral valve recipients. Approximately two thirds of both aortic and mitral valve implants were reported as mechanical. Reported use of anticoagulative agents was significantly more common in recipients of mechanical than of bioprosthetic valves. The single most common reported reason for prosthetic valve implantation was rheumatic heart disease. These data provide useful epidemiologic and public health planning information on prosthetic heart valve use. PMID- 7787477 TI - Concomitant cerebral, brachiocephalic trunk, and cardiac revascularization. An unusual case. AB - Extensive transthoracic brachiocephalic revascularization is rarely performed. Instances of this operation performed concomitantly with cardiac revascularization and carotid endarterectomy have been reported in fewer than 10 cases in the literature. We report the case of a patient requiring complex brachiocephalic revascularization associated with coronary bypass grafting and a left carotid endarterectomy. PMID- 7787478 TI - First experience with cardiomyoplasty in Ukraine. AB - We have been studying feasible surgical alternatives for treating congestive heart failure, including the use of cardiomyoplasty. In this operation, skeletal muscles are conditioned, through electrical stimulation, to provide active tension on diseased myocardium, which improves left ventricular performance and ultimately increases cardiac output. We performed cardiomyoplasty in a 37-year old man with severe ischemic cardiomyopathy. He was discharged from the hospital 2.5 months after the operation, and he did not require medical therapy. We believe this to be the 1st cardiomyoplasty performed in Ukraine. PMID- 7787479 TI - Family physician maternity care. PMID- 7787480 TI - Family practice obstetrics. PMID- 7787481 TI - Potential for abuse. PMID- 7787482 TI - Guideline interpretation varies. PMID- 7787483 TI - External controls limit effectiveness. PMID- 7787484 TI - Misconceived ideas. PMID- 7787485 TI - Differing diagnostic beliefs. PMID- 7787486 TI - Health care clinics in Cambodia. PMID- 7787487 TI - Radiology rounds. Tracheoesophageal fistula. PMID- 7787488 TI - Dermacase. Contact photodermatitis. PMID- 7787489 TI - Consultation in family practice obstetrics. AB - PURPOSE: To examine the types of non-low-risk obstetric patients managed by family physicians in urban teaching hospitals, and to determine indications for consultation for women at low risk when labour began. METHOD: Retrospective chart review for all patients delivered by family physicians in three downtown Toronto teaching hospitals during 1 year. RESULTS: Of 1710 cases, 595 (34.8%) were classified as non-low risk, with the main indications being postdates (> 42 weeks) (19.9%); pregnancy-induced hypertension (19.3%); and premature labour (< 37 weeks) (14.8%). Of the 1115 low-risk patients, 363 (32.6%) had an intrapartum consultation, usually for failure to progress (50.1%) or fetal distress (12.7%). More than 80% of intrapartum consultations were associated with induction and augmentation of labour. CONCLUSION: Family physicians can continue to care for many non-low-risk women, usually with the help of obstetricians. Consultations were obtained for many women at low risk. We need to reevaluate whether some mandatory consultations are necessary in family practice obstetrics. PMID- 7787490 TI - Family medicine in a tertiary care hospital. Obstetrical outcomes and interventions. AB - OBJECTIVE: To examine the rates of obstetrical complications and interventions among patients managed or comanaged by family physicians. DESIGN: Case series. Retrospective review of hospital records. SETTING: Victoria Hospital, a tertiary care centre affiliated with the University of Western Ontario in London, Ont. PARTICIPANTS: Five hundred forty-two women in labour admitted consecutively by family physicians from October 1, 1990, to September 31, 1991. There were no exclusions based on antenatal risk. MAIN OUTCOME MEASURES: Degree of risk on admission, and rates of cesarean sections, inductions, epidurals, forceps deliveries, episiotomies, perineal tears, postpartum hemorrhages, and postpartum fever for mothers. For newborns, Apgar scores and rate of need for a pediatric critical care unit or special observation nursery. RESULTS: Except for rates of inductions and episiotomies, which were lower than those reported elsewhere, results were all comparable to those in previous North American studies of low risk family medicine obstetric patients. CONCLUSION: Family physicians care for women with a range of antenatal risks. Even when practising in tertiary care environments, family physicians can minimize many obstetrical interventions while maintaining good maternal and neonatal outcomes. PMID- 7787491 TI - Family practice obstetrics in a teaching hospital. Does a tertiary care environment make a difference? AB - OBJECTIVE: To determine referral rates, to study the nature of consultations with obstetricians, and to examine how both patient and physician characteristics affect referrals. DESIGN: Case series. Retrospective review of hospital records. SETTING: Victoria Hospital, a tertiary care centre affiliated with the University of Western Ontario in London, Ont. PARTICIPANTS: Five hundred forty-two women admitted consecutively for delivery under the care of family physicians from October 1, 1990, to September 31, 1991. OUTCOME MEASURE: The number and types of obstetrical consultations obtained for the study population. RESULTS: Of the 50.7% of cases requiring consultation, half were delivered by obstetricians. The most common reasons for consultation were failure to progress in labour, induction of labour, posterior presentation, fetal distress, and pregnancy induced hypertension. The most common reasons for obstetricians to attend delivery were to perform forceps rotations and cesarean sections. CONCLUSIONS: Parity and risk classification were the two most important factors for predicting whether consultation would occur. The high rate of consultation in this study might relate to ease of access to consultation in a tertiary care environment. More study is needed to examine the reasons for consultation because it seems that some of the situations for which obstetricians were consulted could have been safely managed by family physicians. PMID- 7787492 TI - Family practice obstetrics in a community hospital. AB - OBJECTIVE: To review obstetric care provided by family physicians and to determine why they transfer patients to obstetricians. DESIGN: Retrospective chart review. SETTING: Obstetrics department of a regional non-academic community hospital PATIENTS: Of 683 women booked with family physicians for obstetrical care, 601 were admitted by family physicians and 82 were transferred to obstetricians before admission. MAIN OUTCOME MEASURES: Risk score, induction, augmentation, consultation, forceps delivery, cesarean section, episiotomy, epidural anaesthesia, narcotic analgesia, neonatal birth weight and Apgar scores, and maternal complications. RESULTS: Family physicians' patients had good maternal and neonatal outcomes; spontaneous delivery rate was 82%; cesarean section rate was 9%. Women transferred from family physicians to obstetricians before admission for delivery had a cesarean section rate of 63%. CONCLUSIONS: Family physicians provided total obstetric care to most women in this community and transferred patients to obstetricians for expected reasons. Community hospitals with family physicians highly involved in providing obstetric care are likely ideal institutions for training future family physicians. PMID- 7787493 TI - Hypertension in pregnancy. AB - Hypertension occurs in 7% to 10% of pregnancies. It is associated with increased risk of maternal and fetal complications. Early diagnosis in the office by careful attention to signs and symptoms could result in adequate management. Delivery provides the only care for this disease process. Recently, low-dose acetylsalicylic acid has been used in high-risk situations to prevent the development of preeclampsia. PMID- 7787494 TI - Postpolio syndrome. Unusual disease in rural family practice. AB - Postpolio syndrome is a sequela of paralytic poliomyelitis seen in approximately 25% of polio victims. Because the symptoms are nonspecific, it can be difficult to diagnose. Getting information about diagnosis and treatment of unusual conditions in rural and remote regions can be difficult, and physicians sometimes find themselves in the position of being the on-site "expert." Physicians must make difficult decisions with patients and their families about life-giving therapies, advance directives, and the like. PMID- 7787495 TI - Cardiopulmonary resuscitation. Not for all terminally ill patients. AB - Where there are clear clinical indications that a patient suffering from a terminal illness would not benefit from cardiopulmonary resuscitation, there is no legal or ethical requirement that CPR be discussed with the patient as a treatment option or that CPR be administered if the patient stops breathing or suffers cardiac arrest. PMID- 7787496 TI - Sotalol-induced bradycardia reversed by glucagon. AB - Glucagon is considered the drug of choice for treating bradycardia and hypotension encountered during beta-blocker poisoning. Its potential usefulness in reversing adverse effects encountered during therapeutic dosing with beta blockers has not been well characterized. We present a case of sotalol-induced bradycardia reversed by glucagon. PMID- 7787497 TI - Practical tips on postpolio syndrome. PMID- 7787498 TI - A public/private partnership in the quest for quality: development of cerebrovascular disease practice guidelines and review criteria. AB - The development of Uniform Clinical Data Set (UCDS) algorithms for cerebrovascular disease can serve as a model for cooperation between government agencies and physician organizations in the development of clinical guidelines and the translation of practice guidelines into review criteria. UCDS is a computerized system of data collection and case finding developed by the Health Care Financing Administration (HCFA) to standardize the Peer Review Organization screening process for potential utilization and quality problems. Input on the cerebrovascular disease algorithms was provided through the American Medical Association UCDS Advisory Panel and the American Academy of Neurology Task Force on Hospital Utilization for Stroke. Physician organizations were successful in identifying problematic areas, improving the original algorithms, suggesting new issues for development, and deleting inappropriate or misdirected algorithms. Since HCFA modified the cerebrovascular disease algorithms in response to feedback, physician organizations have had an important impact on algorithm development. Unfortunately, the process for algorithm review was often complicated, inefficient, and slow. This process is reviewed, problems and constraints are discussed, and specific recommendations are given for improving the process. PMID- 7787499 TI - The legal status of clinical practice parameters: an updated annotated bibliography. AB - In response to extensive speculation about the probable liability implications for health care providers of the formal creation and dissemination of explicit practice parameters of guidelines, I prepared several years ago an annotated bibliography of emerging literature on that topic (1). Since preparation of that catalogue, little meaningful clarification of these issues has emerged from the courts, legislatures, or regulatory agencies. PMID- 7787500 TI - Reengineering quality for health care reform. PMID- 7787501 TI - An empirical test of the structure, process, and outcome quality paradigm using resident-based, nursing facility assessment data. AB - This study distinguishes between organizational characteristics, regarded as exogenous structural indicators of quality, and those identified as endogenous indicators of structural care (SC), and investigates the degree to which measures of SC vary by ownership mode (defined by four combinations of chain affiliation and profit status) for 142 certified and licensed nursing facilities (NFs) in a southern state. Structural care measures include: licensed and unlicensed staffing, licensed therapists, and case mix-adjusted direct care expenditures. In addition, seven (four process and three outcome) facility-level, risk-adjusted process, and outcome quality scales are developed from 39 resident-level quality indicators. A causal mode of NF quality arranged according to the structure, process and outcome paradigm is specified and estimated using path analysis. Organizational data derive from the 1991 Medicaid Cost Report; process and outcome quality measures were developed from the Minimum Data Set Plus Resident Assessment Instrument. Using the percentage of Medicaid and private pay residents as covariates, there was a significant overall multivariate effect due to ownership mode on the SC measures. Although there were several significant direct effects, the overall path model was unconfirmed. The multivariate results suggest that some organizational characteristics of structure quality may be more appropriately considered exogenous to causal quality models and therefore have indirect (versus direct) effects on process or outcome quality indicators. The path analysis implies that the structure-process-outcome paradigm may not accurately capture the way NF health care is delivered. Research which considers alternate NF quality paradigms needs to be done with samples that are more representative of national proportions of each ownership mode. PMID- 7787502 TI - Severity-adjusted differences in hospital utilization by gender. AB - Gender-based differences in hospital use may result from biological differences or may suggest problems of access to health services and quality of care. We hypothesized that there should be no difference in hospital care between men and women, given the same diagnosis. Hospitalizations were characterized by severity of illness, as this may indicate the timeliness of hospital care. Hospitalizations may be too late (with higher severity of illness) resulting in long stays and high costs, or too early (with lower severity of illness) resulting in care that could be given in alternative treatment settings. Three abdominal conditions were examined which could be misdiagnosed or confused with other diseases involving the female reproductive system: appendicitis, diverticulitis, and cholecystitis. The National Hospital Discharge Survey (NHDS) was used for analysis. Disease staging was used to assign a severity of illness indicator, ranging from stage 1 (conditions with no complications) to stage 3 (multiple site involvement, poor prognosis). For each disease, the percentage of discharges and the age-adjusted discharge rate per 1000 population was examined by stage of illness and gender. For appendectomy, there was a significantly greater percentage of men at stage 1 (lower severity) compared to women (73% versus 67%). For diverticular disease, women had higher proportions of stage 2/3 discharges than men for both medical and surgical hospitalizations. For cholecystitis, women had a greater percentage of hospitalizations at stage 1 than men, notably for surgical treatment (63% compared with 38%), although more men were admitted at stage 2 for both medical and surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787503 TI - Use of follow-up services by patients referred from a walk-in unit: how can patient compliance be improved? AB - Timely use of necessary follow-up services is an important dimension of ambulatory care quality. Using a hospital-based walk-in center, this study identified patients who were referred for follow-up care and examined factors related to compliance with these referrals. The participants were 696 adults seen in a hospital-based walk-in unit between June 1, 1992, and December 1, 1992. Patients completed a self-administered questionnaire including questions about sociodemographic characteristics, prior use of health services, and the Medical Outcomes Study (MOS) 36-Item Health Survey. Medical findings, follow-up recommendations, insurance status, and compliance with follow-up referrals were ascertained using chart review, the hospital's computing system, and clinic records. Fifty percent of the patients were referred for follow-up medical care; 55% of these complied with follow-up referrals. Factors associated with referral for follow-up care included older age, inability to afford a physician, longer duration of chief complaint, the patient's belief that follow-up care would be needed, and worse MOS pain score. The most important factor associated with compliance with follow-up referral was scheduling appointments while patients were still in the walk-in unit. Patients with such scheduled appointments were almost 10 times more likely than others to receive follow-up (adjusted odds ratio = 9.6, 95% confidence interval = 4.4-21.2). The most important step a provider can take to improve compliance with follow-up referral is to schedule appointments before patients are sent home. This should presumably improve quality of ambulatory care. PMID- 7787504 TI - Emergency department utilization in a large pediatric group practice. AB - The effect of a triage and care system, which employs continued patient education, alternatives to emergency department (ED) care for nonemergent problems, and close cooperation between ED staff and the primary care physician on inappropriate ED use, was analyzed for three groups of patients: (a) Medicaid patients, all of whom had unrestricted access to the ED; (b) group A patients who required prior physician approval and copayments for all ED services; and (c) patients enrolled in group B who were responsible for copayments only and did not require prior physician approval for ED use. Two hundred ninety-nine (299) charts were prospectively reviewed for age, payer status, date, time of visit, diagnosis, outcome of visit, and severity of illness. Medicaid patients utilized the ED much more than expected, compared to either group A or B patients (P < 0.001). Expected rates of utilization were based upon that particular group's representation in a medical associate's patient panel, which was based upon patient billing data. Medicaid patients were significantly younger than group A or B patients (P < 0.001) and had lower severity scores (P = 0.04). Our triage and care system failed to alter patterns of ED utilization for Medicaid patients. PMID- 7787505 TI - A managed care model for home infusion therapy. AB - Home infusion therapy began in response to the medical needs of the patients. In the traditional model, products and services were delivered in the home on a physician's prescription. Limitations related to medical quality management and cost were recognized in this model. Because of these limitations, the changes that continue to occur in health care delivery and the increase in number and acuity of patients requiring non-hospital services, a managed care model was conceived and implemented at the University of Minnesota Medical School and Hospital. This model emphasizes physician-based case management, total quality management, a point of contact medical information system, outcomes assessment and management, and research and education activities designed to evaluate and improve home infusion therapies. The model was implemented through a public private partnership. This application of managed care to home infusion therapies is described in this communication. PMID- 7787506 TI - [Industrial hygiene and occupational diseases in chemical industry at present]. AB - The working conditions of workers engaged in chemical industry today make them be at risk of an occupational disease whose early manifestation can be detected by modern techniques of medical investigations, such as electromyography, electron spirometry, allergic, immunological and neuropsychological tests. The preventive trend in occupational medicine should be in progress by developing the system of biological and hygienic monitoring techniques for those getting in contact with noxious chemicals and by improving the legal bases for creating safe working conditions with allowance made for new economic relations. PMID- 7787507 TI - [Health status of dwellers of cities and towns with developed chemical industry]. AB - Assessing the physical development of children residing in the developed chemical industrial town has revealed that more than a fourth of the children examined are abreast of their biological age and that there is a trend for reducing the number of those who have the level of biological development which corresponds to their age. In the total morbidity pattern among children, respiratory diseases rank first, whose proportion increases in the higher air-polluted areas. A comprehensive assessment shows that the overwhelming majority (88-93%) belong to Health Groups II-IY, which is indicative of the unfavourable environmental factors of the town. The predictive calculation makes it possible to determine possible changes in the morbidity rates due to the identified diseases. The morbidity rate shows 4-6 increases per each unit of changes in the complex indicator of environmental pollution. PMID- 7787508 TI - [Dioxins in the environment]. PMID- 7787511 TI - [Ecological hygiene--a science of global health]. AB - The paper defines ecological hygiene, a science that combines a preventive trend and comprehensive ecological analysis of man-made changes occurring in the biosphere. Ecological hygiene may be regarded as a science of global human health in relation to ecological situations, of modes of its maintenance, promotion, and improvement. As for its application, ecological hygiene may be determined as a complex of medical preventive research subjects whose purpose is to maintain and promote health by preventing diseases and premature aging. To apply this approach, ecological hygiene studies the environment and its influence on the human body, reveals unfavourable environmental factors and defines the maximum acceptable levels of their influence, works out recommendation how to eliminate unfavourable factors and how to rationally apply useful ones. PMID- 7787510 TI - [Probability of health impairment by exposure to chemicals at the level of sanitary standards and the problem of individual sensitivity]. AB - The paper briefly outlines the problems in estimating the probability of the population's health impairments caused to the individual person's hypersensitivity due do their genetic and their acquired properties when it is chemically exposed at the level of the maximum allowable concentrations. In connection with the environmental situation, it is quite necessary to concentrate everybody's attention on palliative antichemical protective measures. PMID- 7787509 TI - [Effects of chemical agents on the immunity status of workers at Novomoskovsk enterprises]. AB - A comprehensive study was made of the body's immunological and microbiological responses to industrial health hazards at chemical enterprises. For this, a total of 284 workers from the Novomoskovsk Bytchim and Orgsintez Production Associations were investigated by the conventional procedures. The workers were found to have immunological changes at the cellular and humoral levels as compared with the persons who were not engaged in chemical industry. There are also changes in the structure of the intestinal microflora at the expense of higher quantities of opportunistic microbes. The findings suggest that the workers of chemical enterprises experience great immunological influences of chemical compounds in their working places, despite the existing safety and protection measures. A number of proposals have been introduced to prevent immunological and microbiological changes in this group of persons. PMID- 7787512 TI - [Interactions of various amino acids, dipeptides and glutathione with hypochlorite anion (CLO-)]. AB - The specific features of interaction between sodium hypochlorite and various amino compounds were examined. It is shown that in the first reaction munite, methionine and glutathione are the most active in neutralizing hypochlorite anion, while histidine, glycine, alanine, dipeptides and taurine are less active. The chloroamino complexes formed by dipeptides and taurine are the most resistant. PMID- 7787514 TI - [Free and esterified epidermal cholesterol in psoriasis]. AB - The levels of epidermal total, free and esterified cholesterol were studied in psoriatic patients. Lipids were isolated from the areas of psoriatic lesions and from the normally appearing epidermis by the authors' non-invasive surface extractive method. The quantity of cholesterol was given in microgram per square centimeter. Fifty six and 11 healthy persons were examined. The skin cholesterol levels were twice-four-fold higher in the patients than in the healthy subjects. The same levels were noted from the areas of lesion and from normally appearing epidermis. The proportion of an esterified fraction decreased mainly in the normally appearing epidermis areas, especially in severe psoriasis. The role of the findings was also discussed. PMID- 7787513 TI - [Molecular mechanisms of the effects of sodium hypochlorite on thrombocytes and lipoproteins]. AB - Hypochlorite seems to inhibit platelet aggregation in the platelet-rich plasma (PRP) by modifying fibrinogen receptors. The hypochlorite-inactivated isolated platelets are completely repaired by native plasma. Platelet aggregation in PRP is suppressed by hypochlorite by its direct interaction with cells and indirectly due to plasma modification. The indirect action of hypochlorite is a reversible reaction between the platelet active groups and the products of plasma modification. The reaction may involve sulphur-containing groups. The spin-probe method shows that hypochlorite penetrates into the lipid phase of human blood lipoproteins. It initiates lipid peroxidation and causes the disturbance of the lipid structure and the protein please. PMID- 7787515 TI - [Specific hemosorption, kinetics and physiological effects]. AB - The paper covers the physicochemical and clinicophysiological aspects of hemosorption. It proposes mathematical models of blood elimination kinetics of substances which have different affinities for plasma proteins and cellular receptors. It also describes the processes occurring onto the surface of hemosorbents on their contact with blood. It is attempted to associate these processes with some immunomodulating effects of hemoperfusion. PMID- 7787516 TI - [Methodical approaches to the assessment of population's domestic exposure to chemicals]. AB - The paper deals with the specific action of biocidal agents of household chemistry as part of population's chemical loading. A concept of evaluation of disinfectants on human health was formulated and its guidelines are substantiated. For this, the author proposes to use criteria for membrane damaging and immunodepressive effect based on the non-invasive test-systems to identify the immunometabolic status of the body. He also defines the ways of searching the approaches to identifying a life-threatening abnormality in either prenosological status. PMID- 7787517 TI - [Mechanisms of natural detoxication and antioxidant protection]. AB - This paper considers the mechanisms of energy-dependent and synchronized detoxication and antioxidative defense (AOD) when synchronized detoxication and antioxidative defense (AOD) when the body is exposed to chemicals. It emphasizes the role of glutathione as a binder of this system involving in the regulation of this activity. It also discusses the mechanisms that define the reliability and efficiency of detoxication and AOD. The paper discusses whether the body's resistance to technogenic toxicants can be enhanced by using metabolic precursors of glutathione and other natural and (or) synthetic agents activating natural detoxication and AOD. PMID- 7787518 TI - BMJ on the internet. PMID- 7787519 TI - Ebola virus. PMID- 7787520 TI - Spinal cord injuries in rugby union players. PMID- 7787521 TI - Primary care at last for Brazil? PMID- 7787522 TI - Corneal transplantation in Britain. PMID- 7787523 TI - Recertifying general practitioners. PMID- 7787524 TI - Cooperating, not competing, to improve health care. PMID- 7787526 TI - First "no win, no fee" case to go to Lords. PMID- 7787525 TI - US religious groups oppose gene patents. PMID- 7787527 TI - Britain ranks poorly for cancer survival rates. PMID- 7787528 TI - Ebola threat eases. PMID- 7787529 TI - Britain to boost competitiveness and science. PMID- 7787530 TI - Traffic victims call for help. PMID- 7787531 TI - Overseas doctors coming to Britain need language test. PMID- 7787532 TI - Spanish doctors strike over pay. PMID- 7787533 TI - Consent is not always essential, say Dutch experts. PMID- 7787534 TI - New infection control measures miss the point. PMID- 7787535 TI - Patient packs to come on stream in Britain. PMID- 7787536 TI - Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain. AB - OBJECTIVES: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN: Cross sectional twin study. SETTING: Twin population based in Britain. SUBJECTS: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS: The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis. PMID- 7787538 TI - Prevalence and outcome of symptomatic carotid lesions in young adults. National Research Council Study Group. AB - OBJECTIVE: To estimate the prevalence and outcome of symptomatic internal carotid artery lesions in young adults. DESIGN: Multicentre hospital based observational study with five year follow up. SETTING: Seven neurological departments in northern and central Italy. SUBJECTS: 240 patients (115 men) aged 15-44 with a recent transient ischaemic attack or stroke in the carotid territory. MAIN OUTCOME MEASURES: (a) Prevalence of symptomatic internal carotid artery stenosis or occlusion detected by continuous wave Doppler ultrasonography at entry; (b) incidence rates of cerebral, cardiac, and non-vascular death; non-fatal stroke; and non-fatal myocardial infarction. RESULTS: Carotid stenoses of 50-99% and occlusions were found in 38 patients (15.8%). Both conditions were significantly more frequent in patients aged over 35 and in those with hypertension, diabetes mellitus, and stroke at entry. The standardised mortality ratio at five years was 10.5 (95% confidence interval 5.0 to 19.3). Survival of patients with stenoses of 0-49% and occlusions was significantly better than that of patients with stenoses of 50-99%. Carotid stenosis of 50-99% was an independent predictor of death (hazard ratio 7.9; 95% confidence interval 2.2 to 29) and non-fatal stroke (hazard ratio 7.4; 1.5 to 37.4). CONCLUSIONS: The prevalence of carotid stenosis or occlusion in young adults after a cerebrovascular event is low. Though patients with high grade symptomatic carotid stenosis are at risk of non-fetal and fetal events, patients with internal artery occlusion apparently have a benign prognosis. PMID- 7787539 TI - Mental disorders in young and middle aged men who commit suicide. PMID- 7787537 TI - Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open, randomised controlled trial. AB - OBJECTIVE: To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection. DESIGN: Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins. SETTING: Large general hospital in Dublin. PATIENTS: 541 patients admitted for lower respiratory tract infection during one year. Patients represented 87% of admissions with the diagnosis and excluded those who were immunocompromised and patients with severe life threatening infection. MAIN OUTCOME MEASURES: Cure, partial cure, extended antibiotic treatment, change of antibiotic, death, and cost and duration of hospital stay. RESULTS: There were no significant differences between the groups in clinical outcome or mortality (6%). However, patients randomised to oral co amoxiclav had a significantly shorter hospital stay than the two groups given intravenous antibiotic (median 6 v 7 and 9 days respectively). In addition, oral antibiotics were cheaper, easier to administer, and if used routinely in the 800 or so patients admitted annually would lead to savings of around 176,000 pounds a year. CONCLUSIONS: Oral antibiotics in community acquired lower respiratory tract infection are at least as efficacious as intraveous therapy. Their use reduces labour and equipment costs and may lead to earlier discharge from hospital. PMID- 7787541 TI - Balti curries and iron. PMID- 7787540 TI - Children who miss immunisation: implications for eliminating measles. PMID- 7787543 TI - Sociodemographic variables for general practices: use of census data. PMID- 7787542 TI - Need and demand for primary health care: a comparative survey approach. AB - OBJECTIVE: To develop general practice profiles of needs and demand for primary health care. DESIGN: Postal survey of a stratified random sample of 3478 people registered with five general practices. Data from a single practice were compared with data from the remaining four to identify areas of comparative need. SETTING: Five general practices in Lothian. MAIN OUTCOME MEASURES: Differences between the single practice and the comparison practices in terms of social and economic circumstances, limiting long term illness, specific ongoing conditions, minor illness or symptoms, psychosocial problems, discussion of lifestyle, associated use of services. RESULTS: Respondents from the single practice reported higher rates than those in the four comparison practices of ongoing mental health and respiratory problems and use of antidepressants, tranquillisers, or sleeping tablets. Although rates of limiting long term illness and other specific ongoing conditions were comparable, the rates of minor illness or symptoms and psychosocial difficulties were higher in the single practice. Respondents from the single practice were more likely to consult frequently, to have contacted the practice out of normal working hours, and to have discussed psychosocial difficulties with a general practitioner. For any specific ongoing condition or "minor" illness, respondents from the single practice were no more likely to consult. CONCLUSIONS: A comparative survey approach is a useful method of developing an understanding of patterns of need and demand among general practice populations. It has the potential to inform planning within individual general practices and the process of commissioning among general practices within a given area. PMID- 7787544 TI - Diagnosis and management of Clostridium difficile infection. PMID- 7787545 TI - Medical informatics. PMID- 7787546 TI - The death of biomedical journals. PMID- 7787547 TI - Telemedicine: lessons remain unheeded. AB - Telemedicine, the delivery of health care with the patient and health professional at different locations, has been around for over 30 years. Its driving force has been developments in communications technology, and as new communications systems are developed health applications are proposed such as supporting the delivery of primary health care to geographically remote areas or regions underserved through the maldistribution of professional expertise. Despite rapid technological advances, evaluations of such systems have been largely superficial, and more thorough evaluations have failed to show significant advantages for more advanced and expensive technology over older technology such as the telephone. Methods for evaluating the impact of particular technologies on the health care system need to be developed and clearer benefits shown in terms of improved standards of care. PMID- 7787548 TI - Teleradiology. AB - Advances in telecommunications and computer software have led to the development of radiology image transfer systems. Radiologists may now report radiographs at a site distant from that of the examination, in some cases almost instantaneously. Computed tomography, magnetic resonance imaging, and ultrasonography may also be supervised from afar. Developments over the past few decades are reviewed, allowing an understanding of the systems currently available. These include systems that transmit static images and real time video systems that enable interactive supervision from a radiologist at a distant site. The implications for the practice of radiology are discussed and the main areas of development over the next few years explored. PMID- 7787550 TI - South Africa's health. Restructuring South Africa's health care: dilemmas for planners. PMID- 7787551 TI - ABC of asthma. Chronic asthma--general management. PMID- 7787549 TI - Smuggling and cross border shopping of tobacco in Europe. AB - Governments have recently become concerned about cross border shopping and smuggling because it can decrease tax revenue. The tobacco industry predicted that, with the removal of border controls in the European Union, price differences between neighbouring countries would lead to a diversion of tobacco trade, legally and illegally, to countries with cheaper cigarettes. According to them this diversion would be through increased cross border shopping for personal consumption or through increased smuggling of cheap cigarettes from countries with low tax to countries with high tax, where cigarettes are more expensive. These arguments have been used to urge governments not to increase tax on tobacco products. The evidence suggests, however, that cross border shopping is not yet a problem in Europe and that smuggling is not of cheap cigarettes to expensive countries. Instead, more expensive "international" brands are smuggled into northern Europe and sold illegally on the streets of the cheaper countries of southern Europe. PMID- 7787552 TI - Increasing the number of organ transplants. Opting out scheme for donors has support in Britain. PMID- 7787553 TI - Increasing the number of organ transplants. Professionalisation of organ procurement in Spain has increased donors. PMID- 7787554 TI - Establishing a minor illness nurse in a busy general practice. May reduce doctors' workload. PMID- 7787555 TI - Preregistration house officers in general practice. Problems will arise over who pays. PMID- 7787556 TI - Preregistration house officers in general practice. Regulations limit approved institutions for training. PMID- 7787557 TI - Preregistration house officers in general practice. Training in general practice is also important for postregistration doctors. PMID- 7787558 TI - Preregistration house officers in general practice. Posts are purely educational. PMID- 7787560 TI - The fibromyalgia syndrome. Electroacupuncture is a potentially valuable treatment. PMID- 7787559 TI - Services for cleft lip and palate. Surgical caseload is only one variable that influences outcome. PMID- 7787561 TI - The fibromyalgia syndrome. Outcome is good with minimal intervention. PMID- 7787562 TI - Private prescribing of controlled drugs needs closer scrutiny. PMID- 7787563 TI - Unreliability of reports of hypoglycaemia by diabetic patients. Hundreds of case reports suggest a problem with human insulin. PMID- 7787564 TI - Unreliability of reports of hypoglycaemia by diabetic patients. Hypoglycaemia was validated. PMID- 7787565 TI - Drug users' views on general practitioners. PMID- 7787566 TI - Methadone maintenance treatment. PMID- 7787567 TI - Environmental lead and children's intelligence. Studies included in the meta analysis are not representative. PMID- 7787568 TI - Environmental lead and children's intelligence. Britain must replace its lead pipes to meet WHO standards for drinking water. PMID- 7787569 TI - Emergency care in general practice. PMID- 7787570 TI - Childhood antecedents of schizophrenia. PMID- 7787572 TI - Reperfusion injury after myocardial infarction. PMID- 7787571 TI - Limitations of randomised controlled trials. PMID- 7787573 TI - Sleep related vehicle accidents. PMID- 7787574 TI - Screening overseas students for tuberculosis. PMID- 7787575 TI - A global health disaster network is needed. PMID- 7787576 TI - GPs accept patients' vote on fundholding. PMID- 7787577 TI - Rationing intensive care. Data from one high dependency unit supports their effectiveness. PMID- 7787578 TI - Torture in Israel. PMID- 7787579 TI - Does debriefing after psychological trauma work? PMID- 7787580 TI - New equities of information in an electronic age. PMID- 7787581 TI - Reliability of the Snellen chart. PMID- 7787582 TI - Genetic traits in common diseases. PMID- 7787583 TI - Health care rationing. PMID- 7787584 TI - Dutch drop plans for contraceptive pill payments. PMID- 7787585 TI - Audit commission defines NHS management costs. PMID- 7787586 TI - 14,000 preventable deaths in Australian hospitals. PMID- 7787587 TI - Israeli smoking ban succeeds in 80% of adults at work. PMID- 7787588 TI - Children affected by HIV need more help. PMID- 7787589 TI - EU's alcohol subsidies come under attack. PMID- 7787590 TI - Funding to follow students into the community. PMID- 7787591 TI - Report criticises French AIDS "charlatans". PMID- 7787592 TI - Republicans turn health reform into a revolution. PMID- 7787593 TI - Evidence of an association between non-Hodgkin's lymphoma and skin cancer. AB - OBJECTIVE: To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkin's lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non Hodgkin's lymphoma and skin cancer was studied. DESIGN: Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. SETTING: Denmark (1943-89) and Sweden (1958-89). SUBJECTS: Four population based cohorts identified in the nationwide cancer registries (34,641 people with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukaemia, 34,989 with malignant melanoma, 25,980 with squamous cell skin cancer). A total of 562,085 person years were accrued for the analysis. MAIN OUTCOME MEASURES: The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. RESULTS: The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non Hodgkin's lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non Hodgkin's lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. CONCLUSIONS: The occurrence of non-Hodgkin's lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkin's lymphoma in recent decades. PMID- 7787595 TI - The analgesic effect of sucrose in full term infants: a randomised controlled trial. AB - OBJECTIVE: To evaluate the effects of different sucrose concentrations on measures of neonatal pain. DESIGN: Randomised, double blind, placebo controlled trial of sterile water (control) or one of three solutions of sucrose--namely, 12.5%, 25%, and 50% wt/vol. SETTING: Postnatal ward. PATIENTS: 60 healthy infants of gestational age 37-42 weeks and postnatal age 1-6 days randomised to receive 2 ml of one of the four solutions on to the tongue two minutes before heel prick sampling for serum bilirubin concentrations. MAIN OUTCOME MEASURE: Duration of crying over the first three minutes after heel prick. RESULTS: There was a significant reduction in overall crying time and heart rate after three minutes in the babies given 50% sucrose as compared with controls. This was maximal one minute after heel prick in the 50% sucrose group and became statistically significant in the 25% sucrose group at two minutes. There was a significant trend for a reduction in crying time with increasing concentrations of sucrose over the first three minutes. CONCLUSION: Concentrated sucrose solution seems to reduce crying and the autonomic effects of a painful procedure in healthy normal babies. Sucrose may be a useful and safe analgesic for minor procedures in neonates. PMID- 7787594 TI - Somatostatin v placebo in bleeding oesophageal varices: randomised trial and meta analysis. AB - OBJECTIVE: To study whether somatostatin or its derivative octreotide is more effective than placebo for treating bleeding oesophageal varices. METHODS: Randomised, double blind trial and meta-analysis with blinded analysis of data and writing of manuscripts. SETTING: Departments of medical and surgical gastroenterology in Copenhagen. SUBJECTS: Patients suspected of bleeding from oesophageal varices and of having cirrhosis of the liver. MAIN OUTCOME MEASURES: Survival, number of blood transfusions, and use of Sengstaken-Blakemore tube. RESULTS: 86 patients were randomised; in each group 16 died within six weeks (95% confidence interval for difference in mortality--19% to 22%). There were no differences between those treated with somatostatin or placebo in median number of blood transfusions (8 v 5, P = 0.07, 0 to 4 transfusions) or in numbers of patients who needed balloon tamponade (16 v 13, P = 0.54, -11% to 28%). In a meta analysis of three trials involving 290 patients somatostatin had no effect on survival compared with placebo (P = 0.59, odds ratio 1.16; 0.67 to 2.01). For blood transfusions and use of balloon tamponade there was heterogeneity between the trials with no convincing evidence in favour of somatostatin. No placebo controlled trials have been performed with octreotide. CONCLUSION: Within the limited power of this study and meta-analysis we were unable to show a clinical benefit of somatostatin in the emergency treatment of bleeding oesophageal varices. PMID- 7787597 TI - Effect of physical activity on femoral bone density in men. PMID- 7787596 TI - Occurrence of different cancers in patients with Parkinson's disease. PMID- 7787598 TI - The time of death after trauma. PMID- 7787600 TI - Bone densitometry in clinical practice. PMID- 7787599 TI - Community care for demented and non-demented elderly people: a comparison study of financial burden, service use, and unmet needs in family supporters. AB - OBJECTIVE: To measure and compare perceived financial burden, use of services, and perceived unmet service needs of supporters of demented and non-demented elderly people. DESIGN: Comparison study of age and sex matched demented and non demented elderly people and their supporters. SETTING: 25 primary health care teams in Dundee. SUBJECTS: 114 community resident elderly (age over 65) people with dementia, 114 age and sex matched comparators, and the main informal supporter of each elderly person. MAIN OUTCOME MEASURES: Carers' perceptions of financial impact of looking after an old person, service use (from a list of locally available services), unmet service needs, and needs for three types of generic service (help with supervision, housework, or personal care). RESULTS: Financial impact was low, except for extra household expense in the dementia group. There was significantly greater use of mainstream domiciliary and day care services in the dementia group. Dementia was nevertheless associated with a high level of unmet need, mainly for more mainstream support and help with supervision of the elderly person. CONCLUSION: Supervisory care for demented elderly people should be further developed within an expanded domiciliary service to meet supporters needs. PMID- 7787602 TI - The future of the GMC: an interview with Donald Irvine, the new president. Interview by Richard Smith. PMID- 7787603 TI - World Health Organisation: change and progress. PMID- 7787601 TI - Using data from the 1991 census. AB - The 1991 census for England and Wales provides a substantial amount of data on demography, ethnicity, housing tenure, employment status, and other social factors for geographical areas ranging in size from enumeration districts upwards. Many in the health service and in the academic community are making use of the data in the 1991 census. However, users of census data need to be aware of the problems and limitations of these data, which include the format of the data, data modification and suppression, sampling error, and underenumeration. An important innovation of the 1991 census was that the census form included a question on the postcode of respondents; this allowed the Office of Population Censuses and Surveys to produce a postcode-enumeration district look up table which overcomes many of the problems previously encountered in trying to assign postcodes to enumeration districts. The new look up table also includes the grid reference of postcodes, and this will improve the geographical referencing of census data. PMID- 7787605 TI - ABC of asthma. Asthma in children: treatment. PMID- 7787604 TI - Minocycline and pulmonary eosinophilia. PMID- 7787606 TI - Anti-therapeutic community mental health law. Chief medical officer defends the Mental Health Bill. PMID- 7787607 TI - Medical schools and racial discrimination. Comparison between medical schools is unjustified. PMID- 7787608 TI - Medical schools and racial discrimination. Cambridge reveals results. PMID- 7787609 TI - Medical schools and racial discrimination. Sixth formers gamble over medical school choices. PMID- 7787611 TI - Doctors from ethnic minority groups. PMID- 7787612 TI - Investigating racial discrimination in the NHS. PMID- 7787610 TI - Medical schools and racial discrimination. The London Hospital Medical College denies selection bias. PMID- 7787614 TI - Dornase alfa for cystic fibrosis. Patients should not be denied a safe, effective treatment. PMID- 7787613 TI - National measles and rubella vaccination campaign. PMID- 7787615 TI - Screening sperm donors for cystic fibrosis. PMID- 7787616 TI - Dornase alfa for cystic fibrosis. Evidence supporting use of this drug has not yet been published. PMID- 7787617 TI - Assessing health needs in primary care. Morbidity study from general practice provides another source of information. PMID- 7787618 TI - Pain in the hand and wrist. Picture of injection is misleading. PMID- 7787619 TI - Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. PMID- 7787620 TI - Pain in the hand and wrist. Treatment of fractures of the scaphoid. PMID- 7787621 TI - Assessing health needs in primary care. Standardised methods of data collection are required. PMID- 7787622 TI - Assessing health needs in primary care. Chronic diseases need to have standard definitions. PMID- 7787623 TI - Assessing health needs in primary care. Tailor data collection to needs. PMID- 7787624 TI - Babies' deaths linked to suboptimal care. PMID- 7787625 TI - Bullying in schools. PMID- 7787626 TI - Smoking and death. PMID- 7787627 TI - Errors in administration of intravenous drugs. PMID- 7787629 TI - Suppression of medical conditions by Cushing's syndrome. PMID- 7787628 TI - Protection of the individual in biomedical research in Africa. PMID- 7787630 TI - Lord Moran's prescriptions for Churchill. PMID- 7787631 TI - Childhood thyroid cancer since accident at Chernobyl. PMID- 7787633 TI - Psychiatric services for people with learning disabilities. PMID- 7787632 TI - Lessons from the Pearce affair: handling scientific fraud. PMID- 7787634 TI - Family mediation. PMID- 7787636 TI - Consultant struck off for fraudulent claims. PMID- 7787637 TI - Disabled people take care issues to court. PMID- 7787638 TI - Peers define best and worst of NHS research. PMID- 7787635 TI - Their lordships on medical research. PMID- 7787639 TI - India moves towards equal rights for disabled people. PMID- 7787640 TI - Abortion laws cause problems in Poland. PMID- 7787641 TI - Academics call for review of National Lottery's funding. PMID- 7787642 TI - Health ministers to help orphan drugs. PMID- 7787643 TI - Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease. AB - OBJECTIVE: To examine the hypothesis that the increase in fibrinogen concentration and respiratory infections in winter is related to seasonal variations in vitamin C status (assessed with serum ascorbate concentration). DESIGN: Longitudinal study of individuals seen at intervals of two months over one year. SETTING: Cambridge. SUBJECTS: 96 men and women aged 65-74 years living in their own homes. MAIN OUTCOME MEASURES: Haemostatic factors fibrinogen and factor VIIC; acute phase proteins; respiratory symptoms; respiratory function. RESULTS: Mean dietary intake of vitamin C varied from about 65 mg/24 h in winter to 90 mg/24 h in summer; mean serum ascorbate concentration ranged from 50 mumol/l in winter to 60 mumol/l in summer. Serum ascorbate concentration was strongly inversely related to haemostatic factors fibrinogen and factor VIIC as well as to acute phase proteins but not to self reported respiratory symptoms or neutrophil count. Serum ascorbate concentration was also related positively to forced expiratory volume in one second. An increase in dietary vitamin C of 60 mg daily (about one orange) was associated with a decrease in fibrinogen concentrations of 0.15 g/l, equivalent (according to prospective studies) to a decline of approximately 10% in risk of ischaemic heart disease. CONCLUSION: High intake of vitamin C has been suggested as being protective both for respiratory infection and for cardiovascular disease. These findings support the hypothesis that vitamin C may protect against cardiovascular disease through an effect on haemostatic factors at least partly through the response to infection; this may have implications both for our understanding of the pathogenetic mechanisms in respiratory and cardiovascular disease and for the prevention of such conditions. PMID- 7787644 TI - Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. AB - OBJECTIVES: To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. DESIGN: A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. SETTING: Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS: 730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. RESULTS: Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. CONCLUSION: In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease. PMID- 7787645 TI - Risk factors for acanthamoeba keratitis in contact lens users: a case-control study. AB - OBJECTIVE: To investigate reasons for an increase in cases of Acanthamoeba keratitis related to contact lenses. DESIGN: Case-control study. Cases were contact lens related acanthamoeba keratitis patients treated between 1 September 1989 and 31 August 1992. Controls were lens users without lens related disease who presented as new patients to the casualty department from 1 March 1992 to 31 August 1992. All subjects completed a questionnaire detailing lens use and hygiene practices. SETTING: Eye hospital. SUBJECTS: 35 cases with acanthamoeba keratitis and 378 controls. MAIN OUTCOME MEASURES: Relative risks comparing different contact lens types, socioeconomic classification, age, sex, lens use, lens wearing experience, hygiene compliance, and hygiene systems. RESULTS: The crude relative risk for developing acanthamoeba keratitis with the use of daily wear disposable lenses was 49.45 (95% confidence interval 6.53 to 2227; P < 0.001) compared with conventional soft lenses (the referent). Multivariable analysis showed that this increased risk could be largely attributed to lack of disinfection (relative risk 55.86 (10 to 302); P < 0.001) and use of chlorine based disinfection (14.63 (2.8 to 76); P = 0.001) compared with other chemical systems (the referent). None of the other outcome measures showed a significant association. CONCLUSIONS: Both failure to disinfect daily wear soft contact lenses and the use of chlorine release lens disinfection systems, which have little protective effect against the organism, are major risk factors for acanthamoeba keratitis. These risks have been particularly common in disposable lens use. Over 80% of acanthamoeba keratitis could be avoided by the use of lens disinfection systems that are effective against the organism. PMID- 7787646 TI - Macular degeneration and early menopause: a case-control study. PMID- 7787647 TI - Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis. PMID- 7787648 TI - Extracontractual referrals: safety valve or administrative paperchase? AB - OBJECTIVE: To describe the extracontractual referrals of residents of a health authority during a six month period in 1994, identifying the number and cost of emergency and non-emergency referrals, including the number of cases costing more than 20,000 pounds and those cases when payment was refused. DESIGN: Descriptive analysis of all extracontractual referrals submitted to the health authority between 1 April and 30 September 1994. SETTING: A health authority covering a population of 614,000. RESULTS: Payment of 2,583,693 pounds was made to 263 different providers for 2400 episodes of care, of which 1469 were emergencies and 931 were elective or tertiary referrals. Authorisation was granted for an additional 1376 referrals for future treatment but was refused in 713 instances, mostly for technical reasons. Sixteen extracontractual referrals together accounted for over a fifth of total expenditure during the study period. CONCLUSIONS: Handling large numbers of episodes of care on an individual cost per case basis imposes an enormous administrative burden on both purchasers and providers, diverting money away from patient care. Extracontractual referrals also expose health authorities to considerable financial risk and may undermine commissioning strategies. Measures are proposed to limit the number of episodes handled in this way. PMID- 7787649 TI - Hospital investigation of men and women treated for angina. PMID- 7787650 TI - Integrating undergraduate and postgraduate education in general practice: experience in Tayside. AB - Several forces have resulted in the creation in Tayside of the first formally integrated unit of undergraduate and postgraduate education in general practice in the United Kingdom. Forces that helped this integration included the desire for change, national developments in education, financial support through funds set aside to cover the additional cost of teaching, and a management structure which concentrates on shared leadership. Forces that hindered the integration included uneasiness about ideas for reforming traditional structures, institutional inertia, the complexity of financial arrangements, and tensions over priorities. The experience of managing institutional changes in Tayside has been invaluable and will lead to a more cohesive approach to undergraduate teaching, postgraduate training, and the provision of services relevant to the development of general practice. PMID- 7787651 TI - Where should health services go: local authorities versus the NHS? AB - The Association of Metropolitan Authorities has recently proposed that responsibility for the NHS should pass from health authorities to local authorities. One of the fiercest debates at the outset of the NHS was whether the hospitals should be run by local authorities. In the end the minister for health, Aneurin Bevan, decided against local democracy and in favour of a national health service. His arguments included the fact that equality of treatment could not be guaranteed if facilities varied with local finances and that even the largest authorities were not big enough to pool risks and expertise. All these arguments still apply today, and the recent changes in community care provide an insight into how a market model of local authority control might work. The changes have been accompanied by a shift from public to private sector provision and the introduction of charges for services that the NHS once provided free. As important, the willingness and ability of local authorities to raise extra revenue from local taxes and charges affect the service they can provide, so leading to inequalities of provision. Local authorities have yet to make the case that they can preserve the fundamental principles and benefits of the NHS, including its reliance on central taxation and unified funding formulas. PMID- 7787652 TI - Local government and health care: the historical perspective. PMID- 7787653 TI - The case for closer cooperation between local authorities and the NHS. PMID- 7787655 TI - Female genital mutilation in France. PMID- 7787654 TI - Female genital mutilation in Britain. PMID- 7787656 TI - Female genital mutilation in Britain. Why the problem continues in Britain. PMID- 7787658 TI - The shaken infant syndrome. Serious effects of shaking were described in 1971. PMID- 7787659 TI - The shaken infant syndrome. Deal with minor episodes of abuse to prevent more serious injuries. PMID- 7787657 TI - Respiratory medicine. PMID- 7787660 TI - The shaken infant syndrome. Shaking alone may not be responsible for damage. PMID- 7787661 TI - Maternal haemoglobin and birth weight in different ethnic groups. Figure for lower end of range of maximal haemoglobin is too low. PMID- 7787662 TI - Maternal haemoglobin and birth weight in different ethnic groups. Lower haemoglobin may be the result rather than the cause of larger fetuses. PMID- 7787663 TI - Maternal haemoglobin and birth weight in different ethnic groups. Methods used do not support conclusions. PMID- 7787664 TI - Outcomes of neonatal intensive care. PMID- 7787665 TI - Water births. Could saline in the pool reduce the potential hazards? PMID- 7787666 TI - Trends in sudden infant death. The few remaining sudden infant deaths are likely to be explicable and avoidable. PMID- 7787667 TI - Trends in sudden infant death. Infant respiratory death rates mirror sudden infant deaths. PMID- 7787668 TI - Misleading meta-analysis. Public policy is based on results of epidemiological meta-analyses that contradict common sense. PMID- 7787670 TI - Misleading meta-analysis. Registers for clinical trials already exist. PMID- 7787672 TI - Advance directives. Law Commission's report makes no provision for dissenting doctors. PMID- 7787671 TI - Misleading meta-analysis. Variability among studies should be investigated. PMID- 7787669 TI - Fish oils and cardiovascular disease. PMID- 7787673 TI - Accident and emergency radiology. "Rule of two" is outmoded and unhelpful. PMID- 7787674 TI - Advance directives. Incompetence develops gradually. PMID- 7787675 TI - Keyhole surgery. PMID- 7787676 TI - Elderly people and the 1990 act. PMID- 7787677 TI - Failing sick doctors. National Counselling Service for Sick Doctors offers support and help. PMID- 7787678 TI - Medical schools and racial discrimination. PMID- 7787679 TI - Treating mental health problems in health care workers. PMID- 7787680 TI - Failing sick doctors. British Doctors' and Dentists' Group will provide an intervention service from 1 July. PMID- 7787681 TI - Treatment in the air. PMID- 7787683 TI - Trust withdraws allegations against consultant. Trust fostered traditional gender culture. PMID- 7787682 TI - Trust withdraws allegations against consultant. Suspension was waste of talent. PMID- 7787684 TI - [The prediction of the individual chemosensitivity of human malignant tumors: the biological patterns and clinical results]. AB - Individual laboratory prediction of the sensitivity of human neoplasms to chemicals is justified on the basis of the authors' own data and those available in the literature. The potentialities and limitations of methods for individual prediction, as well as clinical results are discussed. Data are given on some biological mechanisms responsible for tumor growth which have been obtained in in vitro and in vivo tests with human tumor tissue and carcinoma cells. Further perspectives of this line of studies are discussed. PMID- 7787685 TI - [Nootropic substances enhance the N-methyl-D-aspartate-induced short-term potentiation of synaptic transmission in rat hippocampal slices]. AB - The nootropic agents pyracetam, ethymisole, N-5-oxynicotinoyl glutamate and beta carboline derivative--ambocarb--enhance short-term potentiation of populational EPSP's amplitude of area CA1 pyramidal neurons in the slices of the rat hippocampus, which is evoked by NMDA. The inhibitors of protein kinases diminish the effect of pyracetam and ethymisole (tolbutamide), as well as all the studied nootropic drugs (polymyxin B and trifluoroperazine). PMID- 7787686 TI - [The effect of calcium channel blockers on animal behavior in tests to study their anxiolytic activity]. AB - The anxiolytic activity of calcium channel blockers (verapamil, nifedipine, cinnarizine, fendiline, and diltiazem) versus diazepam (relanium) was tested in experiments on male [correction of female] mice. Only verapamil (1 mg/kg) and nifedipine (5 mg/kg) were found to increase the number of transitions and reduced the animals' stay in the dark compartment. All the agents in the used doses failed to substantially affect the animals' behavior in the plus-maze. It is suggested that conditions for modelling pathological anxiety rather than natural states are required in the experiments where antianxiety properties are studied. The model of pathological anxiety states is possible in the examination of the action of agents on the effects of routine anxiogenic agents. PMID- 7787687 TI - [The effect of clofelin on the pain syndrome in mandibular trauma]. AB - Oral clopheline (0.000075) noticeably alleviates the pain syndrome and circulatory hyperdynamic state of patients with mandibular fracture. The agent is superior to the conventional combination of 50% analgin (2 ml) and 1% dimedrolum (1 ml) in its efficiency and duration of action. PMID- 7787688 TI - [A comparative study of the anticonvulsant action of a new table salt substitute]. AB - Murine experiments have demonstrated that excess sodium chloride intake has an aggravating effect on the course of convulsions caused by corazolum, thiosemicarbaside and maximum electric shock rather than strychnine. The new sodium chloride substitute hyposol given to animals ad libitum for a fortnight produces an anticonvulsant effect which is more pronounced in corazolum-induced convulsions and potentiates the anticonvulsant effect of diazepam. The official drug sanasol is antagonistic to strychnine and corazolum, but it displays a proconvulsant activity on a thiosemicarbaside model. PMID- 7787689 TI - [The effect of ximedon on cholesterol metabolism and experimental atherosclerosis in rabbits]. AB - The effects produced by the two pyrimidine derivatives pyridinol carbamate (parmidine) and xymedon on cholesterol metabolism and experimental atherosclerosis were comparatively studied in rabbits. The rabbits were fed either a chow containing cholesterol (200 mg/kg body weight) or the same diet also containing xymedon (30 mg/kg body weight) or pyridinol carbamate (30 mg/kg body weight). Total plasma cholesterol showed 5.5- and 4.7-fold increases in the rabbits receiving only cholesterol or cholesterol + pyridinol carbamate, respectively, as compared with that in the animals on a standard laboratory chow. In the rabbits given cholesterol+xymedon, cholesterol levels were 24% less than that in the animals taking cholesterol alone. In these animals, the aortic atherosclerotic damage index (ADI) was equal to 24.1%, which was 1.8-fold less than that in the cholesterol-fed rabbits. In the rabbits given cholesterol+pyridinol carbamate, ADI was decreased by 1.7 times, but it did not differ from that in the hypocholesterolemic rabbits. At the same time xymidone and pyridinol carbamate reduced the hepatic levels of total and esterified cholesterol. To elucidate the mechanism of action of xymedon, it was studied for effects on cholesterol metabolism in cultured rabbit hepatocytes and murine macrophage J774. Xymedon did not alter the esterification and other parameters of cholesterol metabolism in the cultured hepatocytes. It is suggested that the hypocholesterolemic effect was realized at the level of intestinal rather than hepatic cholesterol metabolic changes. The investigations made on the murine macrophage J744 showed that xymedone reduced cholesterol esterification in macrophages, evidently by inhibiting the activity of the enzyme acyl-CoA: cholesterol acyltransferase. The anti-atherosclerotic effect of xymedon seems to result from reductions in plasma cholesterol levels and cholesterol esterification in blood vascular cells. PMID- 7787690 TI - [The effect of the mineral composition of the diet on cholesterol metabolic indices and the experimental correction of propranolol-induced atherogenic dyslipoproteinemia]. AB - Rat experiments have revealed that surplus sodium chloride intake causes dyslipoproteinemia and intensifies the atherogenic action of propranolol. The new antihypertensive and antiedematous table salt substitute, as sanasole exerts its hypocholesterolemic effect. Both dietary salt mixtures eliminates the atherogenic action of beta-adrenoblocker. The application of table salt substitutes may become a convenient and effective agent against risk for atherogenesis. PMID- 7787692 TI - [A mathematical analysis of the cardiac activity indices in patients with ischemic heart disease undergoing antianginal pharmacotherapy]. AB - Taking into account various parameters of heart rhythm variability makes it possible to differentiate patients with ischemic heart disease by their response to antianginal pharmacotherapy. The cardiointervalographic method may be used to predict therapeutical effects in making clinical and pharmacological decisions. PMID- 7787691 TI - [The principles for creating drug preparations of natural origin that stimulate hematopoiesis]. AB - The paper outlines the principles in designing hemostimulators by using glycosamineglycans. Hemostimulating properties of the tested agents is likely to be primarily due to the presence of D-glucuronic acid in their structure. The homotypic mechanisms are largely responsible for all agents' effect in stimulating hemopoiesis. Thus, they all virtually activate the function of the hemopoiesis-inducing microenvironment. In addition, they directly or indirectly stimulate the processes of proliferation and differentiation of precursor cells of erythro- and granulomonocytopoiesis. PMID- 7787693 TI - [The epithelium-dependent mechanism of the bronchodilating action of adrenaline]. AB - The involvement of the epithelium in the adrenergic reactions of airways smooth muscles was studied. The epithelium-dependent pathway of the bronchodilating action of catecholamines, which played a minor role was found to become decisive in some cases. In that case the epithelial inflammatory lesion could be a cause of reducing the response of the bronchi to catecholamines. PMID- 7787694 TI - [The interaction of the converting-enzyme inhibitor captopril with cardiac glycosides in the rat kidney]. AB - Strophanthin (0.1 mg.kg, i.v.) and digoxin (0.1 mg/kg, i.v.) moderately increase blood supply of the renal cortical and medullary layers in unconscious rats and enhance renal excretion of sodium and water. Preadministration of the converting enzyme inhibitor captopril (10 mg/kg/day, per os, for 6 days) promoted vascular dilatation in the inner and outer areas of the medulla, which occurred under the action of these agents and substantially increased their natriuretic and diuretic effects. It is concluded that the renin-angiotension system is directly involved into the mechanism of action of cardiac glycosides in the kidneys, acting as a modulator that prevents their vasodilating and tubular effects. PMID- 7787695 TI - [An evaluation of the efficacy of chronotheray with heparin and kurantil in patients with chronic pyelonephritis]. AB - The effectiveness of traditional therapy (TT) and chronotherapy (CT) with heparin and curantyl was comparatively studied in 80 patients suffering from chronic pyelonephritis. The blood clotting variables were determined every 4 hours before and 2.5-3 weeks after TT and CT in combination with antibacterial therapy. The findings suggest that CT is more effective than TT with heparin and curantyl. With CT, steady-state clinical effects, positive dynamics of laboratory findings and a greater trend to normalization of the circadian organization of hemocoagulation were achieved in earlier periods when lower daily and course doses of the agents were used. PMID- 7787696 TI - [The effect of thalicoside on reproductive function in an experiment]. AB - Talicoside, a triterpene glycoside from Thalictrum minus L., given in an oral dose og 1 mg/kg for 5 days was demonstrated to cause ovulation stimulation induced by intravenously injecting 1.2% solution of copper acetate into the rabbits. The agent enterally administered in a dose of 1 mg/kg to rats for 5 days reduced the levels of luteinizing hormone and elevated serum follicle-stimulating hormone in proestrous and estrous. PMID- 7787697 TI - [The cytochrome P-450-dependent mono-oxygenase system of the liver and interleukin-1 production by the macrophages in adjuvant arthritis in rats under the influence of beta-carotene]. AB - A relationship between the production of interleukin 1 (IL-1) by macrophages from adjuvant-induced arthritic rats and cytochrome P-450-dependent hepatic microsomal monooxygenase was studied. The synthesis of IL-1 by splenic and peritoneal macrophages on day 17 postadjuvant treatment was not altered, but the hepatic cytochrome P-450 levels and monooxygenase activity were significantly decreased. Beta-carotene treatment of arthritic rats reduced hind paw swelling and concurrently stimulated the ability of macrophages to secrete IL-1 and increased the cytochrome P-450 levels and the activity of hepatic monooxygenase. The findings did not establish a definite relationship between the production of IL-1 by systemic macrophages on the one hand, and the hepatic cytochrome P-450 levels a and monooxygenase activity on the other hand. It thus appears that IL1 is unable to play a role of a mediator between the immune system and the hepatic cytochrome P-450-dependent monooxygenase system of rats with adjuvant-induced arthritis. PMID- 7787699 TI - [The limitation of glucose catabolism as a factor in protection during hypoxia]. AB - Violuric acid was first shown to have antihypoxic and antioxidative properties, to exert protective action in sodium nitrite-induced hemic hypoxia. Hepatic glucose and glucogen levels increased, the activity of glucose-6- phosphodihydrogenase enhanced, while that of lactate dehydrogenase and alkaline phosphatase decreased, the content of cAMP restored, whereas cGMP and 2,3 diphosphoglycerate levels decreased to a greater extent. The action of violuric acid was especially evident at the ultrastructural level-the ultrastructure of brush receptor elements in anoxia in the presence of violuric acid's action retained all the features characteristic for intact animals, which was accompanied by a significant accumulation of glycogen in the neuroplasm. PMID- 7787700 TI - [The pharmacokinetics of the new Russian prolonged-action form of diclofenac sodium--Ortopek--in a single oral dose]. AB - Ortopak tablets, 100 mg, were investigated. The pharmacokinetics of Ortopak was studied in 10 rheumatoid arthritis patients after a single oral dose of 100 mg. Ortophenum and voltaren-retard (Ciba-Geigy) were used for comparison. Diclophenac sodium was measured in the patient's plasma by using high performance liquid chromatography. Ortopak was shown to be eliminated from the patient's body much slower than Ortophenum. The bioequivalence of Ortopak versus Ortophenum was 62.7%. The pharmacokinetic properties of Ortopak were similar to those of Voltaren-retard, which were close to those of diclophenac-sodium in the blood plasma within the therapeutic range. PMID- 7787698 TI - [The pharmacological correction of the activity of lipid peroxidation processes in the dynamics of craniocerebral trauma]. AB - Rat experiments have shown that free radical oxidation processes are activated in the cerebral mitochondrial fraction in the dynamics of craniocerebral injury, which appears as accumulation of malonic dialdehyde and disturbed functional interaction of antiradical protection enzymes. These changes are most marked 24 hours after injury. Some GABA-positive drugs and opioid receptor agonists prevent lipid peroxidation activation. The highest efficiency is displayed by piracetam (1 g/kg) and the synthetic enkephalin analogue DSLET (0.1 mg/kg). PMID- 7787701 TI - [The effect of D-penicillamine on the metabolism of the basic substance of the connective tissue and the indices of the liver parenchyma in experimental cirrhosis in rats]. AB - While examining the effects of D-penicillamine [correction of D-penicillin] on the formation of hepatic toxic damage in mature male Wistar rats from the stage of developing cirrhosis to that of the developed one, the author revealed a high antifibrotic activity of the drug which significantly normalized the metabolism of the major agent of the hepatic connective tissue; there was a slight improvement of parenchymal metabolism when the agent was taken for 2 months. There were apparently healthy animals in the experimental group following 4-month course of the therapy. Control rats developed hepatic damage, as evidenced by electron microscopic studies. PMID- 7787703 TI - [The participation of the epiphysis in the organization of resistance to neurotropic agents]. PMID- 7787702 TI - [An experimental evaluation of the behavioral characteristics in the formation of a predilection for alcohol]. AB - A set of correlating indices has been developed to assess alcohol craving in rats who has a free access to it for 24 months. The set includes the estimation of voluntary daily alcohol intake before and after ethanol deprivation and the assessment of rats' behavior in a conflict situation and a plus-maze. The increased intake of alcohol after its deprivation has been established to correlate with a number of punished ethanol lickings in the conflict paradigm and functional locomotor asymmetry in the plus-maze. PMID- 7787704 TI - [The role of the GABAergic system in regulating uterine contractile function and the direction of the search for effective pregnancy-protective agents]. PMID- 7787705 TI - [The sequelae of cytochrome P-450 induction]. PMID- 7787706 TI - [The microsomal system of the liver and cholepoiesis]. PMID- 7787707 TI - [New hepatoprotective agents of natural origin]. PMID- 7787709 TI - Periduodenal panniculitis due to spontaneous rupture of a pancreatic pseudocyst into the duodenum. AB - We report a patient with transient periduodenal panniculitis due to spontaneous rupture of a pancreatic pseudocyst into the duodenum. He developed sudden onset of severe epigastric and back pain with jaundice, mimicking the symptoms of acute pancreatitis. However, the serum and urinary amylase levels did not increase. CT scans showed disappearance of his pseudocyst and periduodenal panniculitis without any evidence of acute pancreatitis. The CT findings of periduodenal panniculitis and his symptoms both improved within 3 weeks. A duodenal fistula leading to the remnant pseudocyst and narrowing of the periduodenal portion of the common bile duct were demonstrated by endoscopic retrograde cholangiopancreatography. PMID- 7787708 TI - Clinical evaluation of gastric fundic gland polyps without familial polyposis coli. AB - BACKGROUND: Assessments were made of 63 cases of fundic gland polyposis (FGP) unassociated with adenomatosis coli. These cases were evaluated by radiological examination over 2 years follow-up. All polyps were pathologically confirmed by endoscopic biopsies. METHODS: Most cases were asymptomatic when diagnosed during mass radiological surveys of the upper gastrointestinal tract. The majority of patients ranged in age from 40-60 years, and the polyps numbered fewer than 20 in 55 cases (87.3%). Polyps were detected in the fundic glands using the congo red test and by biopsies. RESULTS: All serum gastrin values were within the normal range. During the course of this study, the polyps of 13 cases (20.6%) increased and those of three cases (4.8%) decreased or resolved completely. CONCLUSION: From these findings it is considered that FGP are observed in stomachs with less atrophy, and that polyps follow courses in which they increase, decrease, disappear, along with atrophy. PMID- 7787711 TI - Intrahepatic bile duct dilatation secondary to hepatocellular carcinoma: CT features in 10 patients. AB - BACKGROUND: To determine the computed tomographic (CT) features of bile duct obstruction secondary to hepatocellular carcinoma (HCC). METHODS: CT examinations of 10 patients (mean age, 58 years) with bile duct obstruction secondary to HCC were retrospectively reviewed. RESULTS: All tumors were intrahepatic. Eight tumors were well-delineated and two were ill-defined. The largest diameters of tumor ranged from 1.5-6.0 cm (mean, 3.6 cm). All tumors were hypodense before contrast and did not contain calcification. After contrast, four tumors became hypodense, three were isodense, and three were hyperdense to the liver. No tumor demonstrated encapsulation. Diffuse intrahepatic bile duct dilation was observed in seven patients. One patient had extrahepatic bile duct dilatation. Localized bile duct dilatation was observed in three patients, in the hemi-liver which contained the tumor. No tumor invaded the portal vein. CONCLUSION: Although rare, HCC should be included in the differential diagnosis of bile duct obstruction. This diagnosis should be suggested in patients with bile duct obstruction when CT shows an associated intra- or extrahepatic mass. Our results suggest that HCC responsible for bile duct obstruction is remarkable for the absence of encapsulation. PMID- 7787710 TI - Primary sclerosing cholangitis: sonographic findings. AB - BACKGROUND: To determine the value of sonography of the upper abdomen in primary sclerosing cholangitis (PSC). METHODS: In a prospective study of 23 patients with PSC we performed upper abdominal sonography. Sonographic findings of the bile ducts were correlated with endoscopic retrograde cholangiographic (ERC) findings. Signs of advanced disease and complications were also sought. RESULTS: The major limitation of ultrasound was its inability to exclude intrahepatic duct disease. In six patients with multiple strictures and pruning but without dilatations on ERC, sonography showed no intrahepatic duct abnormalities. Extrapheptic duct disease was adequately demonstrated on ultrasound. Mural thickening of the common bile duct (CBD), the hallmark of PSC in the appropriate clinical setting, was demonstrated in 17 of 18 cases with a stenosis on ERC. Ultrasound confirmed advanced disease manifested by signs of portal hypertension in seven patients. Marked nonsegmental intrahepatic duct dilation and the presence of a mass lesion occurred in two of three cases in which complicating cholangiocarcinoma was found. CONCLUSION: Despite its inability to exclude intrahepatic duct disease, sonography is useful in diagnosing and following PSC. PMID- 7787713 TI - Dynamic contrast-enhanced MR imaging of fibrolamellar hepatocellular carcinoma. AB - The magnetic resonance (MR) appearance of fibrolamellar hepatocellular carcinoma (FL-HCC) on T1- and T2-weighted and dynamic serial postgadolinium-DTPA images is reported. Both tumors were large (> 7 cm in shortest dimension) and had central regions of low signal intensity on T1- and T2-weighted images. Diffuse heterogeneous enhancement of the tumors occurred on immediate postcontrast images. Lesions became more homogeneous in enhancement over time, but lack of enhancement of central portions of the tumor persisted. Although persistent lack of enhancement of the tumor scar on late postcontrast MR images may be characteristic of FL-HCC compared with delayed enhancement in focal nodular hyperplasia, the potential similarities between these tumors is stressed. PMID- 7787712 TI - Bile duct involvement in hepatocellular carcinoma: MR demonstration. AB - BACKGROUND: To determine the magnetic resonance (MR) features of hepatocellular carcinoma (HCC) with associated bile duct involvement. METHODS: MR examinations of six patients (mean age, 62 years) demonstrating bile duct involvement due to HCC were retrospectively reviewed and compared to surgical and pathologic findings. RESULTS: Three of the tumors were solitary, and three were multifocal. In two patients, MR showed direct biliary duct invasion by tumor. On T1-weighted MR images, four tumors were hypointense compared to the liver and two were isointense. On T2-weighted MR images, four tumors were hyperintense, and two were isointense. The two tumors studied with dynamic T1-weighted MR images obtained after intravenous administration of a gadolinium chelate, displayed enhancement similar to that of the liver. There was no evidence of a tumor capsule on either unenhanced or enhanced MR images. Intrahepatic bile duct dilatation was seen in five patients. The extrahepatic bile duct was normal in all cases. CONCLUSION: Although rare, HCC should be included when considering the etiology of intrahepatic bile duct obstruction. Imaging features suggestive of the diagnosis by MR include intrabiliary tumor or bile duct obstruction with an associated hepatic mass. PMID- 7787714 TI - MR imaging of intrahepatic cholangiocarcinoma. AB - BACKGROUND: The purpose of this study was to determine the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma. METHODS: MR imaging studies of seven cases of pathologically proven intrahepatic cholangiocarcinoma were retrospectively reviewed. RESULTS: On MR images the tumors presented as a single mass (N = 5) or multiple nodules (N = 2), as well-delineated (N = 5) or ill defined (N = 2), and as nonencapsulated (N = 7). Mean tumor diameter ranged from 6-14 cm (mean, 10 cm). On T1-weighted (TR/TE = 400-600/10-17 msec) images, the tumors were hypointense compared to the liver. The five tumors studied with dynamic MR imaging showed progressive centripetal filling-in after intravenous administration of a gadolinium chelate. On T2-weighted (TR/TE = 2000-2500/80-100 msec) images, all tumors were hyperintense compared to the liver; five were markedly hyperintense and two moderately hyperintense. Vascular encasement, bile duct dilatation within the tumor, and central scar were depicted on MR images in four, three, and two tumors respectively. CONCLUSION: The typical MR appearance of intrahepatic cholangiocarcinoma is a large well-delineated nonencapsulated tumor associated with intrahepatic venous encasement. PMID- 7787715 TI - Cystic peripheral cholangiocarcinoma: sonography and CT. AB - A case of cystic peripheral cholangiocarcinoma is presented. Both sonography and computed tomography (CT) demonstrated a large intrahepatic cystic neoplasm containing an enhancing solid portion. Despite the very rare incidence of this tumor, we believe that cystic degeneration of peripheral cholangiocarcinoma should be considered with these radiologic findings. PMID- 7787717 TI - Chylous ascites: CT and ultrasound appearance. AB - An unusual but pathognomonic appearance of chylous ascites was observed on computed tomographic (CT) and ultrasound examinations of the abdomen in a patient with AIDS and disseminated tuberculosis. The images showed gradual development of fat-fluid level in the peritoneal collection when the patient maintained a recumbent position. The explanation for this phenomenon is provided together with a brief review of pertinent literature. PMID- 7787716 TI - Undifferentiated embryonal sarcoma of the liver treated with chemotherapy: CT imaging in four patients. AB - BACKGROUND: The purpose of this study was to describe the computed tomography (CT) findings of undifferentiated embryonal sarcoma after chemotherapy and to correlate the CT imaging findings with pathologic findings. METHODS: Ten CT images obtained before and after chemotherapy in four patients with hepatic undifferentiated embryonal sarcoma were retrospectively reviewed and correlated with pathologic findings. RESULTS: After chemotherapy, tumor volume decreased by 50-90% and initially nonresectable tumor or gross residual tumor was successfully excised in three patients. In all patients, enhancing peripheral solid portions and septations changed to low-attenuation areas, and in three patients increased or de novo calcifications were found at the periphery of the tumor. Resected pathologic specimen after chemotherapy showed well-encapsulated masses with central necrosis, fibrosis, and dystrophic calcifications. CONCLUSIONS: These CT findings will be useful in monitoring the treatment response of hepatic undifferentiated embryonal sarcoma during chemotherapy. PMID- 7787718 TI - Direct spread of subperitoneal disease into solid organs: radiologic diagnosis. AB - The subperitoneal space is the continuous space interconnecting the peritoneum and retroperitoneum and the abdominal organs. This report expands the concept of direct spread of disease via the subperitoneal space to include direct extension into the solid abdominal viscera (i.e., liver, kidneys, and spleen). Discussion of the anatomy, case presentations, and imaging with computed tomography, ultrasound, and magnetic resonance are presented. This unifying concept provides an understanding for direct spread of disease presenting clinically or being imaged within a solid abdominal organ. PMID- 7787719 TI - Sonography of acute appendicitis in pregnancy. AB - BACKGROUND: Clinical evaluation of acute appendicitis is difficult in pregnant patients. Delay in diagnosis is associated with increased fetal mortality. The purpose of our study was to assess the value of sonography in the diagnosis of acute appendicitis in pregnant women. METHODS: We obtained sonograms in 22 pregnant women suspected of acute appendicitis. All sonograms were performed using graded-compression to detect an enlarged appendix. The sonographic criteria for acute appendicitis were detection of a noncompressible blindended and tubular multilayered structure of maximal diameter greater than 6 mm. RESULTS: The sonographic findings were correlated with surgical findings in seven cases and clinical follow-up in 15 cases. Acute appendicitis was diagnosed by sonography in three of 22 patients, and in all but one was confirmed by surgical and pathologic findings. In the remaining 19 patients, 15 improved on clinical followup; three were shown to have a normal appendix at surgery and one had focal acute inflammation at the tip of the appendix. CONCLUSIONS: Our experience suggests that graded-compression sonography is a useful procedure in pregnant patients suspected of acute appendicitis and has a similar accuracy as in nonpregnant women, especially in the first and second trimester. PMID- 7787721 TI - Turcot's syndrome: a new case in the first decade of life. AB - A case of Turcot's syndrome is described in an 8-year-old girl. Turcot's syndrome is a rare hereditary disease in which malignant glioma of the central nervous system is associated with colonic polyposis. The patient initially presented with a left parietal glioblastoma diagnosed by computed tomography (CT), and was subsequently found to have nonfamilial colonic polyposis. PMID- 7787720 TI - Nonpalpable rectus sheath hematoma clinically masquerading as appendicitis: US and CT diagnosis. AB - Within a period of 5 years, we encountered three patients with a small rectus sheath hematoma, presenting with clinical signs of appendicitis. The rectus sheath hematoma was diagnosed by ultrasound (US) in all three cases and confirmed by computed tomography (CT) in two. None of the hematomas was palpable and in two of three cases in which the patient did not receive anticoagulant therapy. In patients who are sonographically examined for suspected appendicitis, the abdominal wall should be studied as well, to exclude a nonpalpable rectus sheath hematoma. In cases in which a hematoma is found, an unnecessary appendectomy can be prevented. PMID- 7787722 TI - Niemann-Pick disease type C: nodular splenomegaly. AB - Niemann-Pick type C disease (NPCD) is an autosomal recessive storage lipidosis due to a disorder of cholesterol esterification leading to the accumulation of sphingomyelin and cholesterol in the brain, liver, and spleen. The disease is usually diagnosed when neurological symptoms appear. We report an unusual presentation of NPCD in a young asymptomatic adult with isolated nodular splenomegaly. PMID- 7787724 TI - Multilocular cystic renal cell carcinoma presenting as a solid mass: radiologic evaluation. AB - BACKGROUND: Multilocular cystic renal cell carcinomas (MCRCCs) are a recently described variety of renal cell carcinoma with characteristic pathological and clinical features. We found that the radiologic appearances of MCRCCs of smaller size did not fulfill the previously documented criteria of the MCRCCs. This study was conducted to analyze the radiologic characteristics of MCRCCs of smaller sizes. METHODS: The radiologic findings of 13 multilocular cystic renal cell carcinomas of diameter ranging from 10-32 mm (average 22 mm) seen in nine patients were analyzed in correlation with pathologic findings. RESULTS: On US, the tumors were predominantly hyperechoic (11 of 13 tumors) with or without small anechoic areas. Precontrast CT showed the lesions to be either hypodense or hyperdense depending on the presence of hemorrhage. Degree of contrast enhancement was usually slight. The mean increase in CT attenuation was 28 +/- 19 (mean +/- standard deviation) at dynamic phase and 12 +/- 10 at delayed phase. On MR imaging, signal intensities of the tumors were high both on T1- and T2 weighted images (7 of 9 tumors) due to proteinaceous fluid or hemorrhage. Dynamic enhanced MR imaging revealed irregular contrast enhancement within the tumor (5 of 6 tumors). Angiography failed to reveal neovascularity. CONCLUSION: Although multiple cysts were seen within the tumors pathologically, MCRCCs of smaller sizes appeared solid on radiologic examinations. However, contrast enhancement or neovascularity was very slight. PMID- 7787723 TI - Herniation of small bowel through the falciform ligament: CT demonstration. AB - A case of intestinal obstruction with strangulation due to a hernia through a rent in the falciform ligament is presented to emphasize the diagnostic role of CT imaging in patients without previous surgery. PMID- 7787725 TI - Emphysematous pyelonephritis with resultant emphysematous cholecystitis secondary to hematogenous dissemination. AB - Both emphysematous pyelonephritis and emphysematous cholecystitis are uncommon, but potentially fatal, clinical entities. The simultaneous diagnosis of these two entities in the same patient has not previously been reported. In this paper, we describe a 68-year-old diabetic male who presented acutely with emphysematous pyelonephritis and emphysematous cholecystitis. This case demonstrates several important diagnostic and treatment considerations. Additionally, the unique circumstances of this case offer support for the proposal that emphysematous cholecystitis may often be secondary to hematogenous seeding/embolic phenomena rather than obstruction of the cystic duct. Prompt diagnosis is essential, as prompt intervention can minimize mortality and morbidity. PMID- 7787726 TI - Ureteral lymphoma: MRI demonstration. AB - A case of ureteral lymphoma with no other areas of involvement was incidentally discovered on MRI examination. Bilateral ureteral soft tissue infiltration, asymmetrical hydronephrosis, and abnormal enhancement of lymphomatous tissue were noted. A follow-up MRI after chemotherapy demonstrated significant decrease in the size of the periureteral disease and improvement in the extent of hydronephrosis. PMID- 7787727 TI - MRI of pelvic neurofibromatosis. AB - Pelvic neurofibromatosis is a rare disease and rarely involves the prostate. A 19 year-old male presented with irritative and obstructive voiding symptoms. Magnetic resonance imaging showed a large mass extending from the sacral promontory to the perirectal and perivesical spaces and to the proximal root of the penis. The mass also involved the prostate. The characteristics of the mass were highly suggestive for neurofibroma. Prostate biopsy showed neurofibroma, and the immunohistochemistry stain for S-100 protein was positive. PMID- 7787728 TI - Cricopharyngeal bar: myth and reality. PMID- 7787729 TI - Compensatory renal hypertrophy. PMID- 7787730 TI - Barium studies in esophageal cicatricial pemphigoid. AB - BACKGROUND: Cicatricial pemphigoid (CP) (benign mucous membrane pemphigoid) is a rare, blistering disease of skin and mucous membrane. The disease rarely extends to involve the esophagus, and there are only a few cases reported in the radiological literature. The aims of this study were to document the frequency of esophageal involvement and to describe the findings on upper GI barium studies. METHODS: A total of 197 patients with CP were seen at our institution from 1981 to 1991. The clinical and radiological findings of these patients were reviewed and compared with findings reported in the literature. RESULTS: Esophageal involvement was documented in seven patients. Cervical esophageal webs were found in five of the seven patients. Two patients had single esophageal webs while three had multiple webs. Frank strictures of the esophagus were also seen in five patients. These were most common in the cervical esophagus, but strictures were also found in the mid and lower esophagus. Two of the strictures resulted in significant dysphagia and required multiple endoscopic dilatations. One of the dilatations was complicated by mucosal injury, and follow-up barium examination showed dissection of the esophageal mucosa from the cervical esophagus to the esophagogastric junction. One patient demonstrated intramural pseudodiverticulosis in the cervical esophagus. Functional disturbances demonstrated on barium studies included tracheal aspiration in two patients and nasopharyngeal reflux in three. CONCLUSIONS: CP involves the esophagus in approximately 5% of cases. The hypopharynx and cervical esophagus are most commonly involved, but any portion of the esophagus may be involved, and multiple levels of involvement may be seen. Cervical esophageal webs, often multiple or complex, are the most common appearance on barium studies, but frank strictures are also found. Secondary manifestations of esophageal involvement include nasopharyngeal reflux, tracheal aspiration, and intramural pseudodiverticulosis. PMID- 7787731 TI - Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear. AB - We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function. PMID- 7787732 TI - Ileum brush border alkaline phosphatase activity in an experimental model of chronic alcoholism after small bowel proximal resection in the rat. AB - Literature reports that chronically ingested ethanol induces changes in the morphology of the small bowel mucous membranes. It has a topical toxic effect on the epithelium of the proximal jejunum and a blood-borne effect on the epithelium of the ileum because its absorption is almost complete in the stomach, duodenum and proximal jejunum. In addition there are also reports showing stimulation of enterocyte proliferation after segmental intestine resection. In this report we compare a group of rats submitted to resection of the proximal jejunum and fed a liquid diet containing 35% of the total calories intake as ethanol for four weeks to its control pair-fed group. In both groups we studied the mucosal alkaline phosphatase (APase) activity by histochemical as well as biochemical methods. We found a decreased APase activity in the homogenate of the intestinal mucous membrane in the alcoholic group and a reduced enzymatic activity in the brush border of the ileum enterocytes, as demonstrated by histochemical qualitative and densitometric assays. The result suggests that this change in APase activity of the brush border may represent enterocyte immaturity induced by long-standing ethanol intake in the remnant ileum after proximal resection. PMID- 7787733 TI - Mixed culture of pericytes and endothelial cells from fetal microvessels of the human placenta. AB - To explore the role of perivascular cells in angiogenesis and vasomotricity, placental cultures of perivascular cells were performed from calibrated villi excised from term placentas. Microvessels were isolated using repeated digestion of villi by collagenase-dispase and purification by Percoll gradients. Plated on Petri dishes, the microvessels became adherent to the gelatin matrix permitting to cells to proliferate. Cells were harvested and subcultured. Endothelial and pericyte cell lines were identified by phase contrast microscopy. Pericyte number predominated rapidly, the endothelial cells remaining visible. After seven days, cells started to cluster, thus piled up and built numerous nodules. Medium-size oval endothelial cells were stained by anti-von Willebrand factor and anti-IgG coupled to fluorescein. Large cells with irregular border reacted to smooth muscle anti-alpha-actin and anti-IgG coupled to fluorescein. There was no cross reaction of these two cell types with the antibodies. In contrast, nodules were stained by both immunostainings. Endothelial cells reacting to von Willebrand factor antibody were frequently associated to the nodule. The isolation of microvessels from the human placenta described in this study allowed the establishment of cultures of endothelial cells and pericytes that show: i) rapid predominance of pericytes over endothelial cells, ii) formation of nodules, iii) participation of endothelial cells and pericytes to nodules formation. PMID- 7787735 TI - Differential expression of c-fos proto-oncogene in two subclones derived from a human ovarian cancer cell line. AB - The expression of the c-fos proto-oncogene was studied in two sublines of the human ovarian cancer cell line SW626. One subline (SW/B) presents the typical 2.0 kb mRNA which is detectable within 15 min. after serum stimulation of quiescent cells, is inducible by protein synthesis inhibitors and has a half-life of approximately 10-15 min. The other subline (SW/A) does not show the 2.0 kb mRNA, but instead presents a mRNA of higher molecular weight capable of hybridizing with the c-fos probe. This bigger mRNA is neither serum inducible nor sensitive to protein synthesis inhibitors. The presence of this transcript is not due to any gross alteration in the gene structure. Differences were found in the DNA binding proteins obtained from nuclei of the two sublines. A protein able to bind the promoter of c-fos was found in SW/B but not in SW/A. In the latter subline no amplification products were observed using two different sets of primers covering the 3' coding region of the human gene. Conversely, the expected fragments were amplified from mRNA obtained from the SW/B subline. PMID- 7787734 TI - Hypoxia and reoxygenation of brain endothelial cells in vitro: a comparison of biochemical and morphological response. AB - Reactive oxygen species are thought to be important for a variety of pathological processes in the brain. Endothelial cells have been proposed as both a significant source of oxidants and targets of oxidative damage. Therefore, lipid peroxidation (LPO) was investigated and compared to biochemical and morphological alterations in cultured pig brain capillary endothelial cells after hypoxia (120 min. 95% N2/5% CO2) and reoxygenation (30 min. 95% O2/5% CO2). The content of thiobarbituric acid reactive substances (TBARS) representing radical-induced LPO was 2.50 +/- 0.46 after hypoxia and 5.92 +/- 0.54 nmol/mg protein after reoxygenation (p < 0.05 each, vs. normoxic control 1.79 +/- 0.21). During hypoxia, ATP content decreased to 7.9 +/- 1.6 nmol/mg protein; lactate dehydrogenase activity in the incubation solution increased to 0.17 +/- 0.03 U/mg protein; (p < 0.05 vs. control 15.7 +/- 3.1 and 0.09 +/- 0.02, respectively). After hypoxia, morphological changes in lysosomes, multivesicular bodies and vacuoles were observed in contrast to normoxic cells. During reoxygenation, the ATP values were normalized; electron micrographs showed increasing amounts of lysosomes, multivesicular bodies, vacuoles, blebs and lipofuscin granula and lyzed cells. Comparing the biochemical and morphological observations, a sequence of disturbances occurred, in which energy depletion was accompanied and followed, respectively, by membrane destruction, cellular disintegration and an increase in LPO products. These results support the assumption that the damage of brain endothelial cells caused by hypoxia and reoxygenation is accompanied by peroxidation of membrane lipids. PMID- 7787736 TI - Scanning ion microscopy mapping of basement membrane elements and arterioles in the kidney after selenium-silver interaction. AB - The effects of selenium and silver salts was studied by scanning ionic microscopy during experimental argyria mapping of the different basement membrane elements. The ionic microscope (IMS 4F) was equipped with a high resolution spectrometer giving high spatial resolution on the image obtained. After long-term treatment with silver salt alone, silver and sulphur deposits were observed in the membranes. After administration of selenium and silver salt, it was possible to map nitrogen, sulphur, selenium and silver to the glomerular basement membrane as well as to the wall of the kidney arterioles. In the latter, sulphur, selenium and silver were localized only in the elastic laminae of the walls. This process of precipitation of silver deposits in the membrane can be interpreted as process of selenium "detoxification" of the organism. PMID- 7787737 TI - Subcellular localization of gadolinium injected as soluble salt in rats: a microanalytical study. AB - The rare earth gadolinium (Gd) is used in modern industry. Solubilized DTPA Gd and DOTA Gd complexes are used as contrast media in nuclear magnetic resonance imaging. In order to determine the subcellular localization of Gd, rats were injected intraperitoneally with Gd nitrate. Two microanalytic methods, ion microanalysis and electron microprobe, enabled the distribution and the intracellular localization of Gd to be determined in the liver, spleen, bone marrow, kidneys and lung. The results showed: a) a punctual distribution of Gd in the tissues (liver, spleen, bone marrow and lung) as observed by ion microscopy; b) a selective concentration of Gd in the lysosomes of macrophages of the liver (hepatocytes), spleen (macrophages), bone marrow (macrophages) and lung (phagocyte cells), as determined by electron probe X-ray microanalysis. In all these sites the Gd is associated to phosphorus. Results are compared to those found for other rare earths and metal elements. PMID- 7787738 TI - A new procedure for the preparation of highly active melonin from the dry seeds of Cucumis melo L. AB - Melon (Cucumis melo L.) dry seeds contain melonin, a protein that strongly inhibits ribosomes from different prokaryotic and eukaryotic sources including those from melon. The protein was purified by a new method to yield highly active and stable protein preparations that involves chromatography through S-Sepharose Fast Flow, CM-Sepharose, Superdex 75 and Mono-S. Melonin shows important functional properties: 1) its inhibitory effects on translation were irreversible; 2) it is a single unglycosylated polypeptide chain with an apparent M(r) of 22000; 3) it degrades RNA in a dose-dependent way without affecting DNA. In the light of present results melonin can be considered as a new plant RNase of unusual properties. PMID- 7787739 TI - Correlation between membrane potential changes and proliferation of murine peritoneal lymphocytes stimulated by Nocardia water soluble mitogen. AB - A comparative study of Nocardia water soluble mitogen (NWSM) action on membrane potential and proliferation rate of murine peritoneal lymphocytes was performed at various incubation times. The membrane surface charge was evaluated by laser doppler velocimetry (LDV) through the measurement of the cell electrophoretic mobility at different pH values (from pH 5 to 9). We demonstrated that NWSM treatment decreases the lymphocyte membrane potential. This variation reached a maximal level after 24 hrs. at pH 7 and remained unchanged during the 72 hrs. observation. A significant stimulation of lymphocyte proliferation was noted after a 24 hrs. incubation. However, the highest rate of [3H]-thymidine incorporation was observed at 48 hrs. with a subsequent decrease at 72 hrs. On the basis of these data, it is suggested, that membrane potential changes may represent an early important step in the mechanism of lymphocyte activation by NWSM, as it has been shown for some mitogenic compounds. PMID- 7787740 TI - Internalization of Candida albicans and cytoskeletal organization in macrophages and fibroblasts treated with concanavalin A. AB - This paper investigates the ability of macrophages and of non-typically phagocitic cells such as fibroblasts to internalize 51Cr-labelled C. albicans in presence or in absence of lectin concanavalin A (Con A). The results obtained demonstrate that fibroblasts are also able to internalize C. albicans and that this property is potentiated by the presence of Con A. Lectin modifies only the phenotype of the fibroblast, which, poorly attached to the substrate, is globular in shape. Despite reduced cellular spreading, phagocytosis is stimulated by the lectin. In both cell populations, changes in the organization of some cytoskeletal proteins such as tubulin, actin and alpha-actinin are evident during the C. albicans infection; such rearrangements are more evident and longlasting in the fibroblasts treated with Con A. PMID- 7787741 TI - Morphological changes in human erythrocytes induced in vitro by antiarrhythmic drugs. AB - Several hypotheses suggest that the molecular mechanism of action of class I antiarrhythmic drugs (AAD) involve non-specific interactions of these compounds with phospholipid bilayers of the myocardial membrane that surround and functionally modulate ion transport by sodium channels. As a result of these interactions the channel function would be altered. To probe the validity of these hypotheses three AAD with different degrees of lipophilicity were made to interact in vitro with human erythrocytes in a wide range of concentrations. The most lipophilic drug was asocainol (ASOC), the least one was procainamide (PROC) while the lipophilicity of the third, quinidine (QUIN), lay somewhere between the other two. The observations made by scanning electron microscopy (SEM) showed that the three AAD produced profound shape alterations to the incubated erythrocytes. However, the type and intensity of these changes were dependent on the drug under study and its concentration. PMID- 7787742 TI - Electron microscopic lectin histochemistry of the trabecular meshworks in human eyes. AB - Ten normal human trabecular meshworks were examined by electron microscopy using avidin-biotin complex in order to investigate the localization of binding sites of eight lectins. The tissue specimens were fixed in paraformaldehyde and glutaraldehyde mixture and embedded in Lowicryl K4M at low temperature. The ultrathin sections were stained with biotin labelled lectins and colloidal gold labelled streptoavidin and were observed with the conventional transmission electron microscope. Some lectins such as ABA, ConA and DSA were localized on fine fibrils underneath the endothelium of the trabecular wall of the Schlemm's canal, electron-dense cores of elastic fibers, fine granular like materials, basement membranes, collagen fibers and the long-spacing fibers. However, the other lectins such as DBA, SBA, Lotus, UEA-I and RCA60 were not specifically localized in these tissues. From the results it was demonstrated that the differential ultrastructural localization of glycoconjugate residues in the human trabecular meshworks can be revealed using this lectin staining. PMID- 7787744 TI - Spontaneous lipid peroxidation and sperm metabolism during incubation in media simulating the oviductal microenvironment. AB - It has been suggested that along the female genital tract spontaneous lipid peroxidation regulates the limit of the lifetime of spermatozoa. We have studied some aspects of rabbit and mouse spermatozoal metabolism during spontaneous lipid peroxidation in the course of the incubation in media which simulate the oviductal environment. The spermatozoa collected at regular intervals after the beginning of incubation were processed for cytochemical detection of cytochrome oxidase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities. Quantitative cytochemical assays were made in situ in individual spermatozoa by microdensitometry. The cytochrome oxidase activity significantly decreased in both species because of damage to mitochondrial enzymes and membranes by radical and non-radical products of lipid peroxidation. The change in lactate dehydrogenase activity indicates that under our experimental conditions the lipid peroxidation process damages membrane permeability more markedly in mouse spermatozoa. The glucose-6-phosphate dehydrogenase activity, which should influence the concentration of reduced glutathione through production of NADPH, is more extensively enhanced in mouse spermatozoa than in rabbit spermatozoa. This is in agreement with the fact that in mouse spermatozoa the glutathione system is the major protective defence against oxidative damage while in rabbit spermatozoa it is superoxide dismutase. PMID- 7787743 TI - Effects of preservation solutions on cortical and medullary mitochondria of rat kidney. AB - The mitochondria isolated from cortex and medulla of rat kidneys were examined after storage in either Euro-Collins solution, in Bretschneider's histidine tryptophan-ketoglutarat solution or in Belzer's University of Wisconsin solution at 25 degrees C or at 4 degrees C for a maximum of 4 to 24 hrs. Independently to the preservation of the solution used, the storage of the kidneys led to a decrease in state 3 respiration and uncoupled respiration as well as to an increase in the rate of state 4 respiration. The decrease in state 3 respiration ran parallelly to a decrease in adenine nucleotides. For the homogeneous protection of the mitochondria as well from the cortex as from the medulla, the Bretschneider's solution had the best preservative effect at a storage temperature of 25 degrees C as shown by the measured mitochondrial parameters. At 4 degrees C storage temperature, the differences in action with the various examined solutions were markedly smaller. However, compared to the other two solutions, the Euro-Collins solution showed a more favourable protective effect on cortical and medullary mitochondria. PMID- 7787745 TI - Immunosuppression-associated lymphoproliferative disorders in rheumatic patients. AB - The association between rheumatic disease and the occurrence of hematolymphoid neoplasms has been a subject of investigation for many years. Recently, we and others have reported the development in rheumatic patients of lymphoproliferative disorders that are similar to those occurring in patients with known immunocompromised states. The lymphoid neoplasms that develop in patients with immunosuppression are characterized by several features including the presence of EBV genome in the neoplastic cells. The fact that lymphomas with features of those occurring in immunosuppressed patients can occur in patients with rheumatic disease suggests that immune system impairment secondary to the rheumatic disease, the treatment given for the rheumatic disease, or to a combination of these factors, might play a role in the development of lymphoma in these patients. This review will first describe the characteristics of lymphoproliferative disorders that occur in patients with known immunocompromised states. It will then review general aspects of lymphomas in rheumatic patients with a focus on more recent reports that have described the development of immunosuppression-associated lymphoproliferative disorders in rheumatic patients. Studies that investigate the relative contribution of the rheumatic disease versus therapy for rheumatic disease in the development of lymphoma in this patient group are still needed. PMID- 7787746 TI - Acute leukemia with structural rearrangements of chromosome 3. AB - Cytogenetic investigations have distinguished at least 3 distinct clinical cytogenetic syndromes of hematopoietic malignancy with structural rearrangement of 3q. The majority of cases have breakpoints at both 3q21 and 3q26, frequently associated with monosomy 7, abnormal thrombopoiesis, and adverse outcome. Cases with only one of these breakpoints may have milder features of the syndrome. A subgroup with t(3q;5q) occurs in younger patients, occasionally with megakaryocytic dysplasia but rarely having thrombocytosis. The t(3;21) is encountered in secondary leukemias or after chemotherapy of myeloproliferative disorders. The genetic deregulations associated with each of these syndromes involve distinct genes on 3q. The majority of cases of acute leukemias with 3q rearrangements have a poor prognosis and do not respond to current modes of therapy. PMID- 7787748 TI - Biopathologic features of Hodgkin's disease. AB - The neoplastic nature of Hodgkin's disease (HD) is suggested by several lines of evidence, including aggressive clinical course, presence of proliferating atypical cells morphologically recognized as Hodgkin's and Reed-Sternberg cells (H-RS), aneuploidy, and, in the minority of cases, clonality. Nevertheless, the etiopathogenesis of HD still remains elusive, and probably diverse. This uncertainty is partly due to the peculiar histology of HD lesions, characterised by the paucity of the putative neoplastic cell component, i.e. H-RS cells, admixed to a variety of reactive cells which prevent an exhaustive investigation at molecular level. Nevertheless, the possible involvement of different molecules with oncogenic potential has been recently suggested on the basis of immunohistological and molecular biology studies. These include oncogenes such as bcl-2 and MDM2 and anti-oncogenes such as p53. In addition, a large amount of data has accumulated on the possible role of EBV infection in HD. The colonization of lymphoid tissues by immortalized H-RS cells can account for the derangement of cytokine networks leading to microenvironmental and systemic abnormalities. In addition, a variety of soluble receptors (sIL-2R, sCD30, sTNF R), and adhesion molecules (sICAM-1) are abnormally produced at sites of disease involvement. Some of these molecules still retain the ability to bind their ligands and can potentially contribute to the derangement of immune mechanisms observed in HD. Many of these soluble molecules can also be found in the patient's sera providing new potential prognostic and follow-up parameters in HD patients. The comparative analysis of the same molecules within the tissue, using immunohistochemistry, and in the blood, using immunochemical assays, appears as a promising informative approach. PMID- 7787747 TI - Differential usage of an autoantibody-associated VH gene, VH4-21, by human B-cell tumors. AB - Selection of immunoglobulin variable region genes for recombination in B cells takes place from among those VH and VL gene segments available in the unrearranged germ line repertoire. In the case of neoplastic B cells, there is apparent deviation in the use of V-genes from that expected on a random basis, both for VH and for VL. Also, the preferred V-genes, and their patterns of mutation, differ among the various categories of B-cell tumor possibly reflecting the distinct origins and clonal histories on the individual tumor cells. This review focuses on a single VH gene, VH4-21, which is a member of the VH4 family, and which appears selectively to encode immunoglobulins with autoantibody activity, particularly anti-red cell antibodies. The pattern of usage of this VH gene by B-cell tumors demonstrates clear asymmetry among different tumor types. Also, the mutations detected in this relatively non-polymorphic gene indicate that antigen, possibly autoantigen, may influence the behavior of the tumor cell. PMID- 7787750 TI - Adhesion properties of adult T cell leukemia cells. AB - The interaction between neoplastic as well as normal T cells and vascular endothelial cells which is mediated by adhesion molecules play a key role in their trafficking, localization and infiltration. This brief article reviews our studies on the expression of adhesion molecules on leukemic cells isolated from patients with adult T cell leukemia (ATL) and HTLV-I-infected T cell line cells and on their adhesion to human umbilical vein endothelial cells (HUVEC). Fresh ATL cells expressed lymphocyte function-associated antigen-1 (LFA-1), but the expression of very late antigen-4 (VLA-4) and sialyl-Lewis(x) (SLex) was variable. Sialyl Lewis(a) (SLea) was not detected. Cell adhesion assays using HUVEC and adhesion-blocking antibodies revealed the consistent E-selectin mediated adhesion and variable VLA-4-mediated adhesion of ATL cells to HUVEC. The studies on HTLV-I-infected T cell lines confirmed the above data. These results, together with the detection of E-selectin expression on the endothelium of the skin infiltrated with ATL cells, indicate that E-selectin-mediated adhesion is the major pathway for the adherence of ATL cells to endothelial cells. The possible role of such adhesion in the formation of skin lesions and other clinical manifestations of ATL which result from the infiltration of leukemic cells is discussed. PMID- 7787749 TI - Is there a place for immunotherapy with interleukin-2 to prevent relapse after autologous stem cell transplantation for acute leukemia? AB - Chemotherapy-resistant cells cause disease recurrence in a significant proportion of patients with acute leukemia treated with autologous stem cell transplantation due to the lack of immune-mediated effects which contribute significantly to the prevention of post-treatment disease recurrence. This conclusion is based on the observation that relapse after high dose chemotherapy supported by a stem cell transplant from a twin donor is 3-4 times higher than after transplant from an allogeneic donor. This anti-leukemic mechanism of transplanted donor cells has been termed graft-versus-leukemia (GVL) effect, and efforts are being directed toward utilizing such an immune-mechanism after autologous transplantation. Since interleukin-2 (IL-2) can induce remissions in selected patients with advanced leukemia, it has become a candidate cytokine to be used in attempts to introduce GVL after autologous stem cell transplantation. Here we review the available clinical data with IL-2 and critically evaluate whether IL-2 has a place as adjunct treatment to prevent relapse after autologous transplantation for acute leukemia. PMID- 7787751 TI - Cytokine gene expression after allogeneic bone marrow transplantation. AB - Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787752 TI - Epstein-Barr virus-associated hemophagocytic syndrome. AB - A virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Epstein-Barr virus (EBV) is one candidate for this association but serologic and molecular biologic studies have been lacking in many cases. Although VAHS is generally a benign process, EBV-associated hemophagocytic syndrome (EBV-AHS) is often fatal and has a relatively high mortality rate. Therefore, EBV-AHS must be distinguished from VAHS caused by other viruses. Recent evidence indicates that the pathophysiology in EBV-AHS appears to be mediated by the unrestricted release of cytokines produced by the EBV-infected T cells. Clinical and laboratory findings, the differential diagnosis, virology studies, pathophysiology, and treatment in EBV-AHS are reviewed. PMID- 7787754 TI - Treatment of acute promyelocytic leukemia in patients presenting at Vancouver General Hospital from 1983 to 1992. AB - Between 6/83 and 8/92, 23 of 361 patients (6.4%) presenting at Vancouver General Hospital with acute myelogenous leukemia had acute promyelocytic leukemia (APL). Treatment plan was: 1) induction with high-dose cytosine arabinoside and an intercalator; and 2) consolidation with allogeneic bone marrow transplantation (BMT) for those aged < or = 50 years with a sibling donor or repeat of induction for the the others. Complete remission (CR) was achieved in 20 patients (87%). Eleven patients in CR were eligible for allogeneic BMT; 4 were considered unsuitable, 2 refused, and 5 underwent this treatment--1 died of acute graft versus-host disease, 1 relapsed and 3 are leukemia-free and well 1.6, 3.3 and 3.9 years after diagnosis. Fifteen patients did not undergo allogeneic BMT in CR; 4 received no further treatment and all died, 2 relapsed before consolidation therapy and both died, 1 underwent autologous BMT and died of complications, and 8 received consolidation treatment as planned--1 died of sepsis, 2 relapsed and 5 are leukemia-free and well 1.0, 3.8, 4.5, 4.9 and 8.5 years after diagnosis. The actuarial overall survival for all 23 patients was 38% (95% confidence interval [CI] 18-57%). The actuarial 2-year leukemia-free survival was 60% (95% CI 20-85%) for the 8 patients who underwent consolidation chemotherapy as planned and 53% (95% CI 68-86%) for the 5 patients who underwent allogeneic BMT in CR. These results suggest that patients with APL who are able to undergo consolidation chemotherapy have a relatively good prognosis and allogeneic BMT may reasonably be held in reserve for salvage therapy. PMID- 7787753 TI - Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group. AB - All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both. PMID- 7787755 TI - Cutaneous lymphocytic vasculopathy in lymphoproliferative disorders--a paraneoplastic lymphocytic vasculitis of the skin. AB - In this report the histopathology and the natural history of cutaneous lymphocytic vasculopathy (lymphocytic vasculitis) in patients with lymphoproliferative diseases, is described. Between January 1986 and June 1992, 116 patients with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (CLL) were followed. Among them 3 patients with NHL, one with angioimmunoblastic lymphadenopathy/lymphoma and 7 with CLL developed cutaneous vasculitic changes during the course of their disease (incidence of 9.5%). All patients had advanced stage disease. Lymphomas were of B-cell origin and either low or intermediate grade. The median time between the diagnosis of NHL or CLL and the appearance of skin manifestations was 18 months. Recurrent vasculitic changes involving exclusively the skin, was characterized by a (maculo)papular rash, most commonly found in the upper and lower extremities. Pruritus of varying intensity was present in 82% of the patients. In the biopsy, all had perivascular and/or vessel wall lymphocytic infiltration of the dermis with occasional red cell extravasation. Immunohistochemical staining revealed that these infiltrates were mainly composed of T-lymphocytes. We conclude, that cutaneous lymphocytic vasculopathy is a relatively common paraneoplastic skin manifestation in patients with lymphoproliferative diseases and histologically is characterized as lymphocytic vasculitis with (peri)vascular infiltration by non-malignant T lymphocytes. PMID- 7787756 TI - Establishment and characterization of a new Ph1-positive chronic myeloid leukemia cell line MC3 with trilineage phenotype and an altered p53 gene. AB - A new Ph1-positive leukemic cell line (MC3) expressing the P210bcr/abl oncoprotein was established from a patient with CML in blast crisis. The MC3 cells showed the trilineage phenotype of myeloid, lymphoid (CD19) and megakaryocytoid lineages, and had a proliferative response to rhIL-1 and rhIL-3 in the serum-free culture. These results and the expression of CD34 indicated that the MC3 cells have characteristics of hematopoietic progenitor cells. Recently, it has been documented that alterations of the p53 gene in leukemic cells are frequently detected during the blast crisis of CML. The MC3 cells contained the altered p53 gene. In addition, the original leukemic cells showed the point-mutational activation of the N-ras gene and an additional chromosomal abnormality inv(3q), but the MC3 cells contained no such abnormalities, indicating that not all of the original leukemic cells had these abnormalities. Thus, the MC3 cell line may provide several insights into investigations of the blast crisis in CML as well as hematopoietic progenitor cells. PMID- 7787757 TI - Acute myeloblastic leukemia associated with an intermediate state between the healthy carrier state and adult T-cell leukemia. AB - This report describes an intermediate state between the human T-cell lymphotropic virus type I (HTLV-I) healthy carrier and adult T-cell Leukemia (ATL) who developed acute myeloblastic leukemia (AML, FAB subtype M2). The polyclonal integration of HTLV-I proviral DNA was demonstrated in the peripheral blood lymphoid cells, whereas AML cells had no HTLV-I proviral DNA. The patient achieved remission after combination chemotherapy but cells with lobulated nuclei persist at a low level and the polyclonal integration of HTLV-I proviral DNA is still demonstrated. We suggest that the patients with the integration of HTLV-I proviral DNA might develop secondary neoplasms more frequently than healthy carriers and this case stresses the need to exercise caution with these patients. The relationship between HTLV-I and AML is briefly discussed. PMID- 7787760 TI - Receptors on astrocytes--what possible functions? AB - Receptors for transmitters, as varied as those expressed by neurons, have been described on primary astrocyte cultures prepared from new-born rats and mice. A variety of functional effects and considerable cell-to-cell and regional heterogeneity have been observed for such receptors in vitro. The various systems available for studying the presence and properties of receptors on astrocytes in situ, and the results from these studies, are discussed. Much fewer studies using these more difficult systems have been done. So far, some resemblances and differences between in situ and in vitro work have been observed. More of these in situ studies, to supplement the ongoing in vitro work, are needed to enable us to determine unequivocally which receptors are present on astrocytes, and their functions in vivo. If there is cell-to-cell and CNS regional heterogeneity in vivo comparable to that seen in vitro, these analyses will be very complex. To illustrate the importance and variety of receptor-linked functions, a number of suggestions are made in this commentary, based on current proposals for the roles of astrocytes. However, it is argued that we need to have a more complete understanding of astrocyte functions in vivo, before we can really understand the functional significance of astrocyte receptors. PMID- 7787759 TI - Kinins and kinin receptors in the nervous system. AB - Kinins, including bradykinin and kallidin, are peptides that are produced and act at the site of tissue injury or inflammation. They induce a variety of effects via the activation of specific B1 or B2 receptors that are coupled to a number of biochemical transduction mechanisms. In the periphery the actions of kinins include vasodilatation, increased vascular permeability and the stimulation of immune cells and peptide-containing sensory neurones to induce pain and a number of neuropeptide-induced reflexes. Mechanisms for kinin synthesis are also present in the CNS where kinins are likely to initiate a similar cascade of events, including an increase in blood flow and plasma leakage. Kinins are potent stimulators of neural and neuroglial tissues to induce the synthesis and release of other pro-inflammatory mediators such as prostanoids and cytotoxins (cytokines, free radicals, nitric oxide). These events lead to neural tissue damage as well as long lasting disturbances in blood-brain barrier function. Animal models for CNS trauma and ischaemia show that increases in kinin activity can be reversed either by kinin receptor antagonists or by the inhibition of kinin production. A number of other central actions have been attributed to kinins including an effect on pain signalling, both within the brain (which may be related to vascular headache) and within the spinal dorsal horn where primary afferent nociceptors can be stimulated. Kinins also appear to play a role in cardiovascular regulation especially during chronic spontaneous hypertension. Presently, however, direct evidence is lacking for the release of kinins in pathophysiological conditions of the CNS and it is not known whether spinal or central neurones, other than afferent nerve terminals, are sensitive to kinins. A more detailed examination of the effects of kinins and their central pharmacology is necessary. It is also important to determine whether the inhibition of kinin activity will alleviate CNS inflammation and whether kinin receptor antagonists are useful in pathological conditions of the CNS. PMID- 7787758 TI - Anaplastic myeloma. AB - Anaplastic myeloma (AM) represents a rare variety of multiple myeloma (MM) with poor prognosis. One case with special interest is reported, which presented with manifestations due to the extramedullary localization and arose in the absence of an initial diagnosis of MM. In addition, differential diagnosis was based on morphological and immunocytochemical findings while treatment with radio chemotherapy had no effect on the extramedullary sites. PMID- 7787761 TI - Interaction between [3H]flunitrazepam and [3H]GABA binding in the cerebellum of reeler mice. AB - It has been shown that in the cerebellum of reeler mutant mice GABA levels and GABA uptake increase while GABA binding decreases. This study shows that in the cerebellum of these mutants there is also an increase of benzodiazepine receptors. This increase is observed in cerebellar homogenates, in nuclei and in membranes. The increase in the density of central (i.e. clonazepam displacable) benzodiazepine receptors is primarily reflected in binding sites located in the GABA-receptor complex. In comparison to wild-type, GABA-modulin extracted from reeler cerebellum inhibits with a greater potency [3H]GABA binding. The increase in the central-type of benzodiazepine binding and its interaction with GABA binding, observed in cerebellar membranes, is interpreted as a functional response to the decrease in GABA binding and may reflect benzodiazepine receptor condensation and/or changes of subunit composition of the GABA/benzodiazepine receptor complex. The enhanced activity of reeler GABA-modulin reflects a functional response to the increased GABA levels in reeler cerebellum. The increase of the peripheral-type (i.e. PK 11195 displacable) of benzodiazepine receptors is probably due to metabolic changes that may accompany reeler cerebellar mutation. Differences in nuclear benzodiazepine binding between reeler and wild-type mice add a physiological importance to the nuclear binding of this drug. PMID- 7787762 TI - Novel halogenated analogs of tomoxetine that are potent and selective inhibitors of norepinephrine uptake in brain. AB - Halogenated analogs of the potent norepinephrine (NE) uptake inhibitor, tomoxetine, were synthesized and their affinities for the serotonin (5HT) and NE uptake sites evaluated. One of the most potent was the 2-iodo substituted analog (289306) that inhibited [3H]tomoxetine binding to rat cerebral cortex with a Ki of 0.37 nM. The compound also inhibited the uptake of [3H]NE into rat hypothalamic synaptosomes with a Ki of 3.5 nM. This analog was significantly less potent at the 5HT uptake site, as exhibited by a Ki of 25 nM in the inhibition of [3H]paroxetine binding and a Ki of 121 nM in [3H]5HT uptake. The resolved (R) enantiomer (303926) was 10 times more potent as a [3H]NE uptake inhibitor and 29 times more potent as an inhibitor of [3H]tomoxetine binding than the (S) enantiomer (303884). Administration of 289306 to rats prior to an i.c.v. injection of 6-hydroxydopamine prevented the depletion of hypothalamic NE and Epi with ED50 values of 0.28 and 0.47 mg/kg, respectively. Thus, 289306 was a potent inhibitor of NE uptake in vitro and in vivo. In addition, these compounds provide structures for potential ligands for the study of NE uptake sites by autoradiography, PET or SPECT imaging. PMID- 7787763 TI - Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA. AB - Although it has been reported that desipramine affects ion-channel activity of NMDA receptor/ion-channel complexes, the binding sites remain unclear. To identify the binding site, influences of desipramine on NMDA-induced current were examined in Xenopus oocytes injected with rat brain RNA and compared with those of blockers, MK-801, Zn2+ and Mg2+. Application of 100 microM desipramine irreversibly inhibited NMDA-induced inward current as well as 1 microM MK-801. Mg2+ and Zn2+ showed a reversible inhibition. Pretreatment with Mg2+ or Zn2+ abolished the irreversible inhibition of desipramine. In contrast, the irreversible inhibition of desipramine was still observed after application of Mg2+ and Zn2+. These results suggest that Mg2+/Zn2+ and desipramine bind on different sites from each other and affect the cation permeability via different mechanisms. Regarding inhibitory effects of other antidepressant drugs, imipramine and setiptiline were found to markedly inhibit NMDA current, while maprotiline, amitriptyline and lofepramine slightly inhibited the current. Mianserin, a potent antagonist of 5-HT1c receptors, however, had no influence. PMID- 7787764 TI - Interaction of rat brain phosphofructokinase with Alzheimer's beta A4-amyloid. AB - One of the key functional disturbances in incipient dementia of Alzheimer type is the reduction of cerebral glucose utilization. Morphologically the brains of Alzheimer patients are characterized by multiple depositions of beta A4-amyloid mainly within extracellular senile plaques and in the walls of cerebral blood vessels, but also attached to intracellular neurofibrillary tangles. Intracellular beta A4-amyloid may bind to other cellular components. The interaction of beta A4-amyloid with phosphofructokinase, one of the key enzymes in glycolysis, was studied in vitro under various conditions. beta A4-amyloid was found to bind in nanomolar concentrations to phosphofructokinase and decrease its activity. Binding was demonstrated by enzyme linked immunoassays and by gel filtration studies. Inactivation of phosphofructokinase by beta A4-amyloid could only partially be prevented by fructose 6-phosphate. In control experiments no interaction was detectable between lactate dehydrogenase and beta A4-amyloid. PMID- 7787765 TI - Methamphetamine-induced nuclear c-Fos in rat brain regions. AB - To explore the possible robust changes in neuronal activity in dopamine-poor brain regions after an indirect dopamine agonist, methamphetamine, we have investigated its effects on c-fos expression in rat brain using immunocytochemistry of c-Fos. Intraperitoneal injection of methamphetamine (1.6 4.8 mg/kg), but not of saline, induced a widespread nuclear c-Fos-like immunoreactivity in the pyriform cortex and olfactory tubercle with greatest density followed by the II-VI layers of the neocortex, amygdala, hypothalamus, thalamus, nucleus accumbens and striatum. These expression patterns resemble those elicited by amphetamine and suggest that not only the dopamine-rich subcortical regions but also the cerebral cortex may play a crucial role in behavioral abnormality induced by methamphetamine. PMID- 7787766 TI - Rapid and gentle extraction, reconstitution and characterization of microfilament and glia filament from rat astrocytes. AB - We developed gentle and rapid methods for depolymerization and extraction of both microfilament and glia filament separately from a crude cytoskeletal fraction of rat astrocytes. Electron microscopy revealed that the filament reconstituted from the microfilament extract closely resembled F-actin that was formed from G-actin of rabbit skeletal muscle. It was found by immunoblotting analysis that even the reconstituted microfilament-like filaments, which had been purified by affinity chromatography with heavy meromyosin subfragment 1 (S1)-conjugated Sepharose, contained vimentin and glia fibrillary acidic protein (GFAP) besides actin, inferring the interaction between microfilament and glia filament. The filaments (9-10 nm thick) reconstituted from the glia filament extract were composed of actin and other minor components in addition to vimentin and GFAP. Actin, GFAP, 101, 34, 32.5, 30.5, 29.5 and 28 kDa proteins found in the reconstituted glia filament-like filaments were suggested to be glia filament-associated proteins. PMID- 7787768 TI - Glutamatergic receptor kinetics are not altered by perinatal exposure to aspartame. AB - Observation of reduced levels of glutamic acid and aspartic acid in brain of weanling rats exposed perinatally to aspartame prompted a study of the effect of this food additive on glutamatergic receptor kinetics. Aspartame 500 mg/kg/day in drinking water was administered to Sprague-Dawley rats throughout gestation and lactation. Brain was excised from weanlings 20-22 days old, and kinetics of the N methyl-D-aspartate receptor and total glutamatergic binding in cerebral cortex and hippocampus were found to be unaffected by perinatal exposure to high levels of aspartame. Glutamic acid was decreased in both brain regions studied, and aspartic acid was decreased in hippocampus following perinatal aspartame exposure. These changes were reversible when aspartame administration was terminated. It is concluded that perinatal exposure to high doses of aspartame does not alter glutamatergic neurotransmission in cerebral cortex or hippocampus from weanling rats. PMID- 7787767 TI - Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer's disease. AB - The abnormally phosphorylated forms of tau factor are major constituents of neurofibrillary tangles in Alzheimer's disease brain. In order to investigate protein phosphatases which are related to dephosphorylation of abnormal phosphorylation sites, we examined the dephosphorylation of tau factor phosphorylated by three proline-directed type protein kinases. Tau factor phosphorylated by cdc2 kinase and tau protein kinase II was dephosphorylated by the holoenzyme of protein phosphatase 2A and calcineurin, while either the catalytic subunit of protein phosphatase 2A or protein phosphatase 2C could not catalyze the dephosphorylation. From the kinetic analysis, we concluded that tau factors phosphorylated by the protein kinases serve as good substrates for protein phosphatase 2A and calcineurin. On the other hand, tau factor phosphorylated by glycogen synthase kinase 3 alpha was dephosphorylated by the catalytic subunit of protein phosphatases 2A as well as the holoenzyme of protein phosphatase 2A and calcineurin. It has been reported that serines 199, 202 and 396 according to the numbering of the longest human tau isoform are among the major abnormal phosphorylation sites of tau factor. We synthesized two phosphopeptides which contained phosphoserines 199 and 202 or phosphoserine 396 and prepared the polyclonal antibodies specific for the phosphopeptides. Using these antibodies, we confirmed that the holoenzyme of protein phosphatase 2A and calcineurin could dephosphorylate phosphoserines 199, 202 and 396 in tau factor. The catalytic subunit of protein phosphatase 2A could dephosphorylate phosphoserine 396 but not phosphoserines 199 and 202. Neurofibrillary tangles in Alzheimer's disease brain were immunostained with both antibodies but the normal neurons in the normal aged brains were not. The results suggest that protein phosphatase 2A and calcineurin can be involved in the dephosphorylation of abnormal phosphorylation sites in tau factor and that the dephosphorylation of phosphoserine 396 is differently regulated from phosphoserines 199 and 202. PMID- 7787769 TI - Differential characteristics and regulation of arylamine and arylalkylamine N acetyltransferases in the frog retina (Rana perezi). AB - Arylamine N-acetyltransferase activity (A-NAT: E.C.2.3.1.5) from Rana perezi retina was studied using p-phenetidine as specific substrate. Enzyme characteristics and regulation were compared with respect to the arylalkylamine N acetyltransferase (AA-NAT: E.C.2.3.1.87) from the same tissue. A-NAT activity is distributed in both neural retina and choroid-pigmented epithelium complex, showing a 10-fold higher specific activity in neural retina. In contrast, AA-NAT activity is restricted to neural retina. Subcellular localization in neural retina indicated that both enzymatic activities are in the supernatant fraction (39,000 g, 20 min). p-Phenetidine acetylation was linear as a function of the neural retina amount in the assay (1/16 to 1 retina), and it is insensitive to phosphate buffer pH in the range 6.5-8.4. A-NAT kinetic showed a hyperbolic shape for both cosubstrates. Kinetic constants were KM = 11.2 microM, Vmax = 0.49 nmol/h/mg prot. for p-phenetidine (50 microM acetyl-CoA), and KM = 113.4 microM, Vmax = 3.1 nmol/h/mg prot. for acetyl-CoA (5 mM p-phenetidine). The additivity test for both enzymatic activities in retina homogenates demonstrated that both acceptor amines do not compete for the catalytic sites. Serotonin addition in the assay modifies differentially the kinetic characteristics of both enzymes. Serotonin acted as a strong mixed inhibitor, mainly competitive in nature (competitive Ki = 18.1 microM; non-competitive Ki = 1.9 mM) for AA-NAT. However, it acted as a weak inhibitor with respect to A-NAT, mainly non-competitive, (competitive Ki = 5.7 mM; non-competitive Ki = 8.7 mM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787770 TI - Inhibitory effects of lithium ion on intracellular Ca2+ mobilization in the rat hippocampal slices. AB - Lithium is well established as a treatment of manic-depressive illness. As for the mechanism of action of lithium, it is proposed that lithium has effects on intracellular calcium ion (Ca2+) movement. But there are few reports in which the effects of lithium on intracellular Ca2+ movement are observed in the mammalian brain. We therefore examined the effects of lithium on intracellular Ca2+ changes in the rat hippocampal slices with a Ca2+ sensitive dye fura-2, and analyzed by means of a fluorescence microscope, a video-camera and photometrical devices. From the results of treatment with various noradrenergic agonists or antagonists, noradrenaline (NA)-induced intracellular Ca2+ change appears to be mainly mediated by alpha 1-adrenoceptors (AR) rather than alpha 2- or beta-AR. Furthermore, they are considered to be mediated by both alpha 1A-AR and alpha 1B AR, and to be partly dependent on extracellular Ca2+. Lithium decreased NA induced intracellular Ca2+ mobilization by attenuation of T1/2 rather than a change in the peak value, and antagonized ouabain-induced intracellular Ca2+ increase. Lithium may therefore suppress intracellular Ca2+ movement by enhancing the extrusion of intracellular Ca2+. PMID- 7787771 TI - Single cell RT-PCR proceeds without the risk of genomic DNA amplification. AB - We have previously described a method for detection of mRNAs expressed in single cells after patch-clamp recordings. The method, termed single cell RT-PCR, involves aspiration of the cell content, a reverse transcription (RT) step, and a polymerase chain reaction (PCR) using specific primers. Since the nucleus is frequently harvested together with the cytosol, genomic DNA may generate false positive results. Thus, we demonstrated that dilutions containing a few copies of plasmid could be detected by PCR in a range which, according to the Poisson law, suggests that the PCR method can amplify from the two genomic alleles. We performed single cell RT-PCR of intronless GluR2 or GluR5 fragments by comparing cerebellar cell types where these mRNAs are known to be present or absent. For each cell the nucleus was harvested together with the cytosol. Following RT-PCR with GluR5 primers, all Purkinje cells (n = 6) yielded the expected PCR product, whereas it was not generated from any of the granule cells (n = 5). In corresponding experiments with GluR2 primers, we obtained the GluR2 product from all Purkinje cells (n = 5), but not from any of the glial cells (n = 5). These results are in agreement with the known cellular expression of GluR2 and GluR5 mRNAs. We conclude that the single cell RT-PCR method does not amplify the genomic DNA when the nucleus is aspirated together with the cytosol. We suggest that genomic DNA amplification is avoided, because the genomic alleles are not exposed during the procedure. PMID- 7787772 TI - Increased axonal regrowth of lesioned rat sciatic nerve by veratrylguanidine methane sulfonate. AB - Neurotrophic factors appear as essential factors for normal development and repair of the nervous tissue. Veratrylguanidine methane sulfonate, has been shown to induce important neurite outgrowth of cultured dorsal root ganglia isolated from newborn rats. Its action was similar to that of NGF and was found to be additive to that of NGF. In order to see if this compound was able to stimulate axonal growth in adult animals, we examined the effect of this substance on the regeneration of the lesioned sciatic nerve. Using histochemical, immunohistochemical and ultrastructural studies, it is shown that a single intraperitoneal injection of veratrylguanidine methane sulfonate significantly increases the axonal growth during repair of the adult rat sciatic nerve. The efficiency of this substance is explained by its good targeting and long life time in the sciatic nerve. PMID- 7787773 TI - The effect of insulin and insulin-like growth factor-1 on the expression of calretinin and calbindin D-28k in rat embryonic neurons in culture. AB - In a primary culture of rat embryonic neurons, insulin (5 mg/ml) promoted neurite formation between neuron clusters in serum/glial-free simplified medium with a high concentration of transferrin (100 micrograms/ml). Insulin growth factor-1 (IGF-1) exerted a similar effect in the same culture system at a lower dose (100 ng/ml) of insulin. Calretinin has recently been identified as a calcium binding protein expressed predominantly in sensory neurons, which has six calcium binding domains and shows molecular similarity to calbindin D-28k, an intestinal calcium transporter protein also found in the CNS. The effects of insulin and IGF-1 on the expression of calretinin and calbindin D-28k were investigated in rat embryonic neuronal cell culture. When cells were cultured for 2 days, insulin and IGF-1 promoted the expression of both proteins; when cultured for more than 2 days, IGF-1 still exerted a growth factor effect, but insulin decreased the expression of calretinin. Using the present culture system, we demonstrated that the effects of closely related molecules, insulin and IGF-1 which share receptors reciprocally, differed in calretinin and calbindin D-28k expression. Therefore, these two calcium binding proteins may play different physiological roles in the nervous system based either on different molecular mechanisms or switching roles at different stages of CNS development. Amplification based on Western blot employing the streptoavidin-horseradish peroxidase method was applied to detect calretinin and calbindin D-28k in the culture system by an immunoblotting technique. PMID- 7787774 TI - Ascorbate/Fe(3+)-induced peroxidation and inhibition of the binding of A1 adenosine receptor ligands in rat brain membranes. AB - The effect of peroxidation induced by the ascorbate/Fe3+ system on the binding properties of the A1 adenosine receptor, was studied in rat brain membranes, using the agonist, [3H]R-N6-phenylisopropyladenosine ([3H]R-PIA), and the antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX). For the agonist, as well as for the antagonist, the number of binding sites (Bmax) was significantly (P < 0.05) reduced after pretreatment of the membranes with ascorbate/Fe3+. The affinity of the agonist for the binding sites was not statistically modified (P > 0.05) after ascorbate/Fe3+ pretreatment, whereas the Kd value of the antagonist was increased (P < 0.05) by a factor of 2. Ascorbate/Fe3+ pretreatment affected agonist binding in the presence of GTP in a similar way as that observed in the absence of GTP, suggesting that peroxidation also affects agonist binding to A1 adenosine receptors uncoupled to G-proteins. The results suggest that when brain membranes suffer free radical oxidative damage, the adenosine modulation of neuronal activity through A1 receptors could be less efficient. PMID- 7787776 TI - Thiamine homeostasis in neuroblastoma cells. AB - We recently showed that thiamine uptake by neuroblastoma cells is mediated by two saturable transport system: the first with high affinity for thiamine (Km = 35 nM) is blocked by veratridine; the other, with low affinity is blocked by Ca2+. The driving force for thiamine uptake is its phosphorylation to thiamine diphosphate (TDP) by thiamine pyrophosphokinase and subsequent binding of this cofactor to apoenzymes. Our results suggest that cells of neuronal origin possess mechanisms regulating the intracellular concentration of thiamine. At low external thiamine, the vitamin is taken up by a high-affinity transporter and pyrophosphorylated in thiamine diphosphate (TDP): this is the TDP pool of slow turnover. An intraover extracellular concentration gradient of free thiamine is observed at low external concentration of the vitamin. At higher external thiamine concentration, TDP accumulation is limited by the binding capacity to the apoenzymes and unbound TDP (i.e. a small pool of fast turnover) is quickly hydrolyzed. Thiamine is slowly released by the cells by at least two different mechanisms. The first, accounting for a maximum of 50% of total thiamine release, is stimulated by external thiamine and is blocked by veratridine, suggesting that it is a self-exchange mechanism catalyzed by the high affinity thiamine transporter. The remaining thiamine efflux is neither sensitive to veratridine nor to Ca2+ and its mechanism is unknown. About 25% of intracellular thiamine is not released, even after treatment of the cells with digitonin, thus maintaining an apparent gradient. This suggests a binding or sequestration in intracellular compartments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787775 TI - Multiple neurotrophic factors including NGF-like activity in nerve regeneration chamber fluids. AB - Silicone nerve regeneration chambers were implanted between the cut ends of the sciatic nerve of adult rats. Neurotrophic activities in cell-free fluids collected from the chambers were determined using bioassays for survival of embryonic chick ciliary and sympathetic neurons in culture. Separation by molecular exclusion HPLC of the components of fluids collected 1, 2 or 3 days after implantation revealed the presence of a multitude of neurotrophic factors differing in their molecular weights, specificity towards the two types of neurons, and time course. Antiserum to nerve growth factor partially blocked sympathetic activity of fluids collected at 1 day. Affinity purified antibody was also effective and completely eliminated bioactivity of HPLC fractions corresponding to the molecular weight of nerve growth factor. The presence in the fluids of 13-18 and 20-32 kD components active towards ciliary neurons is consistent with the release of fibroblast growth factor and ciliary neurotrophic factor respectively. The stimulation of sympathetic neurons by the 13-18 kD material, and also by 4-6 and 7-11 kD components cannot be entirely accounted for by known factors. This study demonstrates that a number of neurotrophic factors, which differ in their specificity towards sympathetic and parasympathetic neurons, are made available to the region of axonal regrowth over the first few days of regeneration. Contrary to earlier reports, nerve growth factor-like activity was shown to be present in nerve regeneration chambers. PMID- 7787778 TI - rHuGM-CSF after high-dose chemotherapy in post-remission acute leukemia. AB - Post-remission high-dose chemotherapy has been an important advance in the treatment of adult acute leukemia (AAL). Without the use of colony-stimulating factors (CSFs) in this program, the mortality rate varies from 5 to 17%, and infectious complications arise in more than 50%. These findings limit the widespread use of such forms of therapy. The use of high-dose ara-C (HIDAC) alone or in combination with other drugs is the most common regimen studied, however neither other drug combinations nor the addition of supporting CSFs have been extensively explored. For this reason we studied the effect of high-dose cyclosphosphamide-etoposide (CECY) plus recombinant human granulocyte-macrophage (rHuGM)-CSF with the intention of decreasing morbimortality and prolonging disease-free survival (DFS). Since 1992 we have included 51 complete remission patients with AAL in the CECY plus rHuGM-CSF protocol. The maximal myelosuppression occurred in a mean of 6.4 days, and the mean days required for absolute neutrophil count recovery was 13 days and for platelets 21 days (p < 0.0001). No toxic deaths occurred and only two serious infectious complications were seen. After two years of follow-up, 50% of de novo acute myelogenous leukemia patients had relapsed at 13 months, and 50% of de novo adult acute lymphocytic leukemia patients had relapsed at 15 months. In a recent update, we have not seen a significant difference when compared to historic groups. The CECY protocol does not appear to be superior in prolonging DFS compared to HIDAC as a post-remission strategy for newly diagnosed AAL. The main difference was the absence of toxic deaths and minimal serious infectious complications in the CECY protocol. Therefore, we suggest that the use of rHuGM-CSF in post-remission programs should be included in future studies. PMID- 7787780 TI - Unstable triplet repeat sequences: a source of cancer mutations? AB - Numerous mutations have been related to various types of cancer. Short tandem repeats (STRs) are repetitive DNA elements that are often polymorphic in normal populations. Triplet repeat expansion has been related pathogenetically to six diseases: fragile X syndrome, fragile X E syndrome, spinobulbar muscular atrophy, myotonic dystrophy, Huntington's disease, and spinocerebellar ataxia type 1. The characteristics of the GC-rich repeat expansion are diverse and result in profound changes in phenotype, sometimes within a single generation in affected families. We expect that simple repeat expansion will cause some cancers based on our knowledge of these unstable DNA sequences in the previously mentioned genes. This may occur by alteration of tumor suppressor gene expression, alteration in coding features of proteins, or change in bystander oncogene expression such as that which occurs with DNA methylation. The demonstrated meiotic instability could link this mechanism of mutation of familial cancer syndromes. The recent discovery of STR instability at multiple sites in hereditary nonpolyposis colon cancer suggests sequence instability may be a factor in cancer progression. Continued identification of candidate genes containing triplet repeats should allow a ready testing of the hypothesis that unstable simple repeat sequences can cause cancer. PMID- 7787779 TI - Platelet glycoprotein IIb gene expression as a model of megakaryocyte-specific expression. AB - Glycoprotein (GP)IIb/IIIa is an integrin complex normally restricted in its expression to platelets and the megakaryocytes from which they are derived. This complex functions as a receptor for fibrinogen and other ligands and is involved in platelet aggregation. The receptor complex is expressed at high levels during final megakaryocyte differentiation. Further, while GPIIIa is expressed in other tissues as part of the vitronectin receptor, GPIIb is only expressed on maturing megakaryocytes and the platelets derived from them. Thus studies of the GPIIb gene may serve as a model of gene regulation during this process. Over the past several years, the genes for both GPIIb and IIIa have been cloned and analyzed. The GPIIb gene contains 30 exons over 18 kilobases (kb). The transcriptional start site has been determined and there does not appear to be a TATA-box immediately upstream of this site. Studies have been done to define regulatory elements upstream of the transcriptional start site. Most of these studies focused on the human promoter and on studies using megakaryocytic cell lines. These studies have defined several important tissue-specific promoter elements including a GATA454 site (454 basepairs upstream of the transcriptional start site that involves a GATA-binding consensus sequence), a GATA54 site and an Ets35 site (that involves an Ets-binding consensus sequence). Expression studies with megakaryocytic cell lines suggest that each of these sites effects expression approximately threefold. Further, an Ets510 site was also described that had a similar effect. While these studies were underway, we pursued studies of the rat 5'-flanking region using a rat primary marrow expression system. Qualitatively, our data support the human data; however, quantitatively, we found significant differences from the human studies done in cell lines. We found that the major tissue-specific promoter element was the GATA454 site. Mutations altering this site result in an approximately fiftyfold drop in expression. In comparison, eliminating the Ets510 site by truncation or point mutation had only a twofold effect on expression. Mutations at the Ets35 site did effect expression at a high level, decreasing expression approximately fifteenfold, while mutations at the GATA54 site effected expression by approximately ninefold. In addition, using 50 bp deletions, we have preliminarily defined two domains from -450 to -351 bp and 150 to -101 bp upstream of the transcriptional start site that effected expression. The former appears to contain a positive regulatory element, while the latter appears to be a silencer element.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7787777 TI - Retention and multilineage expression of human hematopoietic stem cells in human sheep chimeras. AB - We have taken advantage of the permissive environment of the early gestational age fetus to engraft human hematopoietic stem cells (HSC) into preimmune fetal lambs. The resulting chimeras exhibit long-term multilineage engraftment of human cells in the bone marrow (BM) and peripheral blood (PB). Long-term multilineage reconstitution of second generation recipients by human cells isolated from chimeric sheep BM indicates that the engraftment in this model involved long-term repopulating human HSC. The model appears to be sensitive enough to detect relatively small numbers of transplanted HSC from pre- and postnatal human sources. Finally, transplantation of mature T lymphocyte-containing cells from a variety of sources results in lethal graft-versus-host disease (GVHD), analogous to clinical BM transplantation, suggesting that, at least in some respects, the model is biologically relevant. The human-sheep model is promising and may have important advantages over murine models for the in vivo study of normal and abnormal hematopoiesis and as a potential assay system for human HSC. PMID- 7787781 TI - Hematopoietic growth factors for the treatment of severe chronic neutropenia. AB - Severe chronic neutropenia (SCN) is a rare but important cause of recurrent fevers, oropharyngeal ulcerations and severe infections. In three forms of SCN, i.e., congenital neutropenia (Kostmann's syndrome and related syndromes), idiopathic neutropenia (both childhood and adult), and cyclic neutropenia, it is now established that long-term treatment with the hematopoietic growth factor, recombinant human granulocyte colony stimulating factor (rHuG-CSF or Filgrastim), can elevate blood neutrophil counts to the normal range in most patients, with a concomitant reduction in infection-related events including fever, oral ulcerations, antibiotic use and symptoms of inflammation. Treatment with this growth factor causes an increase in the number and maturity of marrow cells of the neutrophilic series; other cell lines are largely unaffected. Marrow stimulation and expansion are reflected by the occurrence of bone pain early in therapy, as well as some increase in spleen size in most cases. Adverse effects of therapy are infrequent in both children and adults, and long-term treatment with daily or every-other-day s.c. injections of rHuG-CSF are well accepted. Because of the risk that some patients with chronic neutropenia may have or develop myelodysplasia and/or leukemia, careful pretreatment evaluations (blood, bone marrow and cytogenetics) and long-term observations are extremely important. An international registry for patients with SCN has been established to maintain records and further investigate these conditions. PMID- 7787782 TI - [Dynamics of the distribution of biological age for various species]. PMID- 7787783 TI - [Mutual position of chromosome 1 homologs in human interphase lymphocyte nuclei]. PMID- 7787784 TI - [Comparative morphometric analysis of neuroglial cells]. PMID- 7787785 TI - [Effect of bioresonance therapy on protein synthesis in human blood lymphocytes]. PMID- 7787786 TI - [Paternal age and lifespan of the offspring]. PMID- 7787787 TI - [The effect of halogenated dibenzo-p-dioxins on the growth of grasses and assessment of the danger of contaminated phytomasses for mammals]. PMID- 7787788 TI - [The effect of methylating lysine residues on properties of complexes of myosin subfragment-1 with ADP and phosphate analogs]. PMID- 7787789 TI - [Binding of the M2-selective antagonist AF-DX 116 with frog myocardial muscarinic receptors]. PMID- 7787790 TI - [Genetic analysis of sterile hybrid D. virilis x D. lummei males]. PMID- 7787791 TI - Proceedings of the SIMEC 94, 3rd Brazilian Symposium on Extracellular Matrix. Rio de Janeiro, Brazil, September 11-14, 1994. PMID- 7787792 TI - On the monophyletic evolution of the metazoa. AB - 1. The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins. Recently we succeeded in cloning some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). 2. G. cydonium contains several lectins and cDNA for two of them (termed LECT-1 and LECT-2) was cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate-binding site of vertebrate S type lectins. Next, we have isolated and characterized a cDNA coding for a receptor tyrosine kinase of class II (GCTK). The deduced amino acid sequence shows two characteristic domains: i) the tyrosine kinase domain and ii) an immunoglobulin-like domain. The latter part shows high homology to the vertebrate type immunoglobulin domain. This result, together with the lectin data, demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. 3. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen, a "homeotic" organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain sequence was successful. The deduced amino acid sequence of G. cydonium showed high homology to chicken and to the Antennapedia sequence from Drosophila melanogaster. 4. These data support the view that the kingdom Animalia is of monophyletic origin. PMID- 7787793 TI - Sequencing of heparan sulfate proteoglycans: identification of variable and constant oligosaccharide regions in eight heparan sulfate proteoglycans of different origins. AB - The sequence of the disaccharide units of eight heparan sulfate proteoglycans of different origins is described. All heparan sulfates contain 5 variable regions made of oligosaccharide blocks of disaccharides, namely, GlcUA(1-4)GlcNAc, GlcUA(1-4)GlcNS, IdoUA (1-4) GlcNS,6S,IdoUA-GlcNAc,6S, and IdoUA,2S(1-4)GlcNS,6S, besides two constant regions made of an internal tetrasaccharide (IdoUA-GlcNAc IdoUA-GlcNS) and monosaccharides (GlcNS, and GlcNS,6S) at the non-reducing terminal. The N-acetylated region of the heparan sulfates is linked to the serine of the protein core through a trisaccharide of Xyl-Gal-Gal. Heparan sulfates differ from one another in terms of the number of disaccharides that compose each block. PMID- 7787794 TI - Proteoglycans in skeletal muscle. AB - 1. Proteoglycans are macromolecules composed of a protein and one or more chains of sulfated carbohydrates, the glycosaminoglycans. Proteoglycans are found on the cell surface and in the extracellular matrix participating in the cell-cell and cell-extracellular matrix interaction. In this review I present the information accumulated in the past years regarding the presence, characteristics, localization, control of expression and alteration in some pathological states of skeletal muscle proteoglycans. 2. This review presents and discusses current information in this area and some projections for the future in four sections: first, the proteoglycans present in embryonic cells and cell lines from skeletal muscle. Second, the presence of proteoglycans in adult skeletal muscles. Third, the regulation of the expression of skeletal muscle proteoglycans, and fourth, skeletal muscle proteoglycans in pathological conditions. PMID- 7787795 TI - Detection of a small proteoglycan present in xiphoid cartilage regions submitted to different biomechanical forces. AB - 1. The effect of biomechanical forces on large proteoglycans and collagen of cartilage has deserved intensive study, enhancing the importance of these molecules to support a better distribution of compressive forces especially in articular cartilage. In the present study, other extracellular matrix components, non-collagenous proteins and small proteoglycans, have been evaluated in terms of biomechanical tension. 2. Different parts of chicken xiphoid cartilage, lateral (R and L) and central (C) portions, which bear different biomechanical tensions, were analyzed. DEAE-cellulose chromatography profiles were similar for R and L portions. SDS-PAGE analyses revealed proteins of 29, 60 and 70 kDa for R and L. The 20- and 70-kDa proteins were not detected in the C portion while the 60-kDa protein was present at a high level. 3. The differences found between lateral (R and L) and central portions of the xiphoid cartilage may be related to the structure of the cartilage which bears higher tension forces than the lateral parts. PMID- 7787796 TI - Matrix in signal transduction and growth factor modulation. AB - The extracellular matrix (ECM) is indispensable for the survival of multicellular organisms. It provides the adherent cells with crucial clues for migration, proliferation and differentiation. These clues are transmitted to the interior of the cell by ECM receptors like the integrins. Signaling by the ECM occurs by induction of assembly and disassembly of cytoskeletal structures or by modulation of classical signal transduction pathways such as activation of phosphatidylinositol-proteases, growth factors and cytokines that are specifically bound to its constituents and thereby stored, localized and modulated in terms of their biological activities. Finally, both the quantity and the quality of growth factor signaling appear to be dependent on the temporal and spatial activation of ECM receptors, supporting the requirement of a crosstalk between matrix and growth factor receptors. PMID- 7787797 TI - Myelopoietic competence of stroma composed of hepatic granuloma-derived connective tissue cells or skin fibroblasts. AB - 1. Connective tissue cells isolated from hepatic granulomas (GR cells), induced in mouse liver tissue by schistosomal infection, are able to sustain myelopoiesis, while other connective tissue cells such as skin fibroblasts (SF) are not. 2. We compared the ability of SF and GR cells to sustain in vitro proliferation of the FDC-P1 myeloid cell line, dependent upon IL-3 or GM-CSF. 3. Only the GR stroma sustained the proliferation of co-cultured FDC-P1 cells. RT PCR analysis showed that both cell lines expressed the message for GM-CSF, but not for IL-3. We showed that GM-CSF was produced by, and remained bound to the cell layer through heparan sulfate; this growth factor could be released by high salt treatment in a biologically active form from both cell types. The same activity could be restored to NaCl-treated GR cells, but not to SF, by incubation with recombinant murine GM-CSF. 4. These results indicate that the ability of connective tissue cells to sustain myelopoiesis depends directly upon the capacity of their heparan sulfate-bearing molecules to bind and present the GM CSF to the target cells in a biologically active form. Alternatively, a yet unidentified set of cell layer-associated molecules may be required for the positive or negative control of the membrane-bound GM-CSF. PMID- 7787798 TI - Thrombospondin: relationship to protease and growth factor/cytokine activity. AB - 1. The finding in the last two years of different proteins presenting structural homology with platelet thrombospondin (TSP-1) has permitted to establish the existence of a set of related genes referred to as thrombospondin family. While much work remains to be done concerning the characterization of the newly described members of the family, careful studies carried out on TSP-1 have been implicating this high molecular weight molecule (420-450 kDa) in a variety of aspects of cellular physiology. 2. The present text discusses the implications of the matrix-bound and fluid TSP-1 forms for cell adhesion and protease activity generation. Their relationships with growth factors in matrices are also discussed. PMID- 7787799 TI - The kinetics of chondroitin 4-sulfate release from stimulated platelets and its relation to thromboxane A2 formation and granule secretion. AB - 1. In platelet rich plasma (PRP), chondroitin 4-sulfate release from platelets occurred after stimulation with ADP (5 microM), collagen (5-10 micrograms/ml), or adrenaline (10 microM). Release started within 60 s and maximum release (0.7-2.0 mg/l) was reached within 180 s. TXA2 formation and dense granule release reached a maximum within 90 s after stimulation. 2. Using washed platelets (1.5 x 10(8) cells/ml), the platelet responses were faster. Release of chondroitin 4-sulfate and TXA2 started within 20-30 s after thrombin addition (100 mU/ml). Maximum release was reached within 60 s in both cases. Dense granule release started in the first 5 s of stimulation (34.6 +/- 12.4%) reaching maximum secretion (74.4 +/ 8.7%) within 60 s. 3. Our results demonstrate that maximal chondroitin 4-sulfate release occurs after the dense granule release reaction in both PRP and washed platelets. This observation suggests that chondroitin 4-sulfate is unlikely to be stored in the dense granules but may be stored in the alpha-granules. PMID- 7787802 TI - Heparan sulfate proteoglycan and control of cell proliferation: enhanced synthesis induced by phorbol ester (PMA) during G(1)-phase. AB - The effect of phorbol 12-myristate-13-acetate (PMA), a tumor-promoting phorbol ester, on the synthesis of proteoglycans of endothelial cells in culture was investigated. This phorbol activates protein kinase C (PKC) when added to cells in culture. PKC, in turn, modulates the activity of growth factors. Using [35S] sulfate or [3H]-glucosamine to label the proteoglycans we have observed a 4-24 fold increase of the heparan sulfate (HS) synthesis in a dose-dependent manner (0 100 ng/ml). Chondroitin sulfate (CS) synthesis was not affected by PMA. The effect of PMA could be completely abolished by a calcium ionophore (A23187). By the use of synchronized cells and PMA pulses at different periods of the cell cycle, as well as [3H]-thymidine incorporation, we were able to show that the enhancement of heparan sulfate synthesis is most prominent during G1. Our data suggest that the release of HS to the medium could be one of the responses of the cell to a mitogenic stimulus. PMID- 7787801 TI - Adhesion to laminin is down-regulated upon retinoic acid-induced F9 cell differentiation: a role for alpha 6/beta 1 integrin. AB - F9 mouse teratocarcinoma cells have a high capacity to adhere to laminin and we identified alpha 6/beta 1 integrin as the principal laminin-binding protein present in these cells. F9 cells differentiated into parietal endoderm when monolayer cultures were treated with retinoic acid and dibutyryl cyclic AMP. In this process a decreased adherence to laminin was observed due to a lower expression of alpha 6/beta 1 integrin on the cell surface. PMID- 7787800 TI - Carbohydrate-binding proteins in cell-matrix interactions. AB - 1. Carbohydrate-dependent interactions have been more extensively studied during the last decade. Although the roles of carbohydrates in cellular functions are still poorly understood, the finding of carbohydrate-binding proteins in animal cells opened a great number of perspectives. 2. Animal lectins are associated with tumor progression, playing a key role in neoplastic cell interactions with endothelial cells and extracellular matrix glycoproteins such as laminin. 3. Here, we review the role of animal lectins in the migrating phenotype of neoplastic cells and normal cells such as T-lymphocytes. PMID- 7787803 TI - Binding of heparin and compound Y to endothelial cells stimulates the synthesis of an antithrombotic heparan sulfate proteoglycan. AB - The mechanism by which heparin and antithrombotic agents, including a cyclic octaphenolsulfonic acid (compound Y), stimulate the synthesis of an antithrombotic heparan sulfate by endothelial cells in culture was investigated. Compound Y increases the amount of heparan sulfate from the cell surface and secreted to the medium by endothelial cells by three-fold. Binding experiments have shown saturation of the endothelial cell receptors at a concentration of 0.16 microM for heparin and 2.7 microM for compound Y. The kinetic binding constants (Ks) for compound Y and heparin were 1,333 nM and 42 nM, respectively. It was also shown that both compounds bind to the same receptors. The Scatchard plots indicated that 1,319 nmoles compound Y and 35 nmoles heparin bound per microgram cell protein, indicating that 40-fold more molecules of compound Y bound to the receptors when compared to heparin. No significant internalization of the compounds was observed. PMID- 7787804 TI - Scanning electron microscopy of acinar cells of rat submandibular salivary glands. AB - 1. The submandibular salivary gland of rats was observed by high-resolution scanning electron microscopy employing the aldehyde-osmium-DMSO-osmium method. 2. The intracellular membranous components and sponge-like structures of basement membrane containing the fine collagen fibrils of acinar cells were clearly identified in three-dimensional images. The granular endoplasmic reticulum and Golgi apparatus showed the luminal surface. The mitochondria were small, ranging in diameter from 0.3 to 0.5 microns, and revealed their cristae. The secretory granules ranged in diameter from 0.3 to 1.4 microns. Ribosome granules were attached to the surfaces of cisterns, and measured 20 to 25 nm in diameter. 3. The contact areas between the acinar cells revealed numerous cytoplasmic protrusions. In the striated duct cells, the mitochondria were arranged vertically and surrounded by basal infoldings of the plasma membranes. At high magnification, the mitochondrial cristae were visualized in their three dimensional characteristics. PMID- 7787805 TI - Biomatrix effect on Sertoli cells phospholipids. AB - In order to investigate the influence of biomatrix on Sertoli cell morphology and on the phospholipids content, these cells were isolated from testes of 15-day old Wistar rats and plated onto plastic coated with extracellular matrix extracted from seminiferous tubules, here denoted biomatrix. When the Sertoli cells were cultured on biomatrix they did not form a monolayer until day 7 of culture, while cells plated onto plastic did so 48 h after plating. On day 5 of culture, Sertoli cells were incubated for 48 h with 5 microCi/ml 32P. There was no difference in 32P incorporation into lipids of cells plated onto biomatrix or plastic. However, there was a larger amount of phospholipid phosphate in cells plated onto biomatrix than onto plastic. When the phospholipids were analyzed by bidimensional thin-layer chromatography, no differences were detected in their distribution; however, there was a significant decrease in the percentage of sphingomyelin in cells plated onto biomatrix when compared to plastic. These results showed that the cells cultured on biomatrix change their phospholipids content, but not their distribution. The importance of a small reduction in sphingomyelin content remains to be investigated. PMID- 7787807 TI - Altered deposition of extracellular matrix components in the skeletal muscle and lymph node of the MDX dystrophic mouse. AB - 1. MDX mice derived from a colony of C57BL/10ScSn mice develop an X-linked recessive muscular dystrophy, thus providing an adequate model to study the pathogenesis of muscular dystrophy. 2. Skeletal myofibers of MDX mutant mice were heterogeneous, with disorganization of myofilaments and the absence of immunolabelling for dystrophin with monoclonal antibody DY4/6D3. 3. Marked deposition of reticulin, collagenic fiber (types, I, IV) and laminin (LN) were consistently present mostly around lesioned and necrotic myofibers associated with an intense inflammatory reaction, whereas strong immunolabelling for TIII-C, TIV-C and FN was often associated with regenerated fibers. 4. During the onset (3 weeks of postnatal life) of disease and height of myonecrosis (5-6 weeks of postnatal life), popliteal lymph nodes showed dense argyrophilic meshwork, intense immunolabelling for collagens types I and IV, FN, LN and enlargement of the hili which were packed with mononuclear cells. Such alterations, albeit less intense, were still observed in MDX mice with 20 weeks of postnatal life. 5. The results support the view that ECM components might be influencing the migration of inflammatory cells and the process of myonecrosis in the skeletal muscle of MDX dystrophic mice. PMID- 7787806 TI - Cell adhesion in muscle. AB - 1. Attachment to extracellular matrix is thought to be particularly important for striated muscle cells, since skeletal and heart muscle have to withstand considerably strong forces. 2. We have recently shown that a defect in a protein of the muscle basement membrane, M-laminin, is correlated with muscular dystrophy in human and mouse. The disease associated with defects in M-laminin is thus analogous to that caused by defects in the cytoskeletal protein, dystrophin, the Duchenne/Becker muscular dystrophy. 3. One may propose the hypothesis that a pathway of interacting proteins is required to connect the cytoskeleton of the muscle fiber to the extracellular matrix, and that a defect in any protein in this chain would result in severe impairment of muscle cell attachment with resulting muscle damage upon use of the muscle. The existence of such chains of proteins may be expected from known mutations in muscle proteins in Drosophila and Caenorhabditis elegans. Some of these mutations cause phenotypes resembling muscular dystrophy in mammals. 4. It will be important to identify all the proteins that are participants in muscle cell attachment, including receptors for M-laminin and proteins associated with these receptors. PMID- 7787808 TI - Use of lectins to evaluate the effects of GaAs softlaser on dog tendon. AB - 1. Lectins labeled with colloidal gold particles were used for the ultrastructural evaluation of the biological effects of GaAs softlaser irradiation on the healing of dog tendon wounds. 2. Six dogs were submitted to tenotomy and tenorrhaphy on the right and left hind legs. All animals received laser irradiation (4 J/cm2) daily for ten days only on the left leg, and the right leg of the same animal was used as control. Biopsies were taken 11, 22 and 40 days after surgery. 3. Laser-irradiated and control tendon tissues were embedded in L.R. White resin and thin sections were incubated in the presence of gold-labeled Arachis hypogaea (PNA), Canavalia ensiformes (Con A) and Triticum vulgare (WGA). 4. In general, the control and laser-irradiated tissues presented homogeneous and similar labelling of heterochromatin, rough endoplasmic reticulum and extracellular matrix. 5. We conclude that GaAs softlaser irradiation does not produce significant changes in the glycosylation of healing tendons. PMID- 7787809 TI - Glycosaminoglycan structure and content differ according to the origins of human tumors. AB - The glycosaminoglycans of the tumor mass and from the urine of patients with a nephroblastoma of embryonic origin (Wilms' tumor) and hypernephroma were analyzed. The urine of patients with Wilms' tumors prior to treatment, and two patients with metastasis contained high levels of hyaluronic acid (2-5 mg/l of urine) when compared to patients after surgery or chemotherapy where the content of hyaluronic acid was less than 0.1 mg/l. Urine of patients with hypernephroma and normal individuals contained even smaller amounts of hyaluronic acid. Normal kidneys contain mainly dermatan sulfate and heparan sulfate, while the hypernephroma and Wilms' tumor contain substantial amounts of chondroitin sulfate. The amount of glycosaminoglycans isolated from Wilms' tumor and hypernephroma were 10 times and 3 times, respectively, greater than normal kidneys. The amounts of hyaluronic acid in Wilms' tumor varied from 56 to 73% whereas normal kidneys contained about 13%. Chondroitin sulfate was also increased in Wilms' tumor and hypernephroma. It corresponded to 11% and 42%, respectively, of the total glycosaminoglycans. These and other findings indicate that the glycosaminoglycans of Wilms' tumors resemble those present during embryonic development of normal tissues whereas those in hypernephroma are typical of other carcinomas of different origins. PMID- 7787811 TI - Extracellular matrix degradation in parasitic diseases. AB - 1. Fibrosis is an important manifestation of several parasitic diseases, but is not irreversible. A marked degree of extracellular matrix degradation can occur after cure of parasitism. Patients with the hepatosplenic form of schistosomiasis undergo considerable resorption of portal fibrosis months or years after curative treatment as demonstrated by ultrasonography and pathological examination. 2. Studies of the post-treatment degradation of extracellular matrix in schistosomal periovular granulomas have demonstrated two forms of collagen degradation: in hepatic granulomas formed during early infection a rapid process occurs, with the extracellular breakdown of fibers and internalization of collagen fragments, whereas during late infection, degradation is slow and is accompanied by focal electrondense and/or lytic changes. 3. Extensive extracellular matrix degradation and resorption occurring after curative treatment was recently described in the liver of a man with advanced visceral leishmaniasis and in the heart of mice with chronic Chagas' disease. PMID- 7787812 TI - Proteoglycans and glycosaminoglycans synthesized by the hepatic granulomas isolated from schistosome-infected mice and by a granuloma-derived connective tissue cell line. AB - 1. This paper summarizes our studies on proteoglycans and glycosaminoglycans in the hepatic fibrosis occurring in schistosomiasis. 2. We have compared proteoglycans and glycosaminoglycans isolated from schistosomal fibrotic granulomas with those obtained from the cellular and extracellular compartments of a murine cell line derived from schistosome-induced granulomas, the primary cell line "GR". 3. Our results have shown some biochemical and structural similarities between proteoglycans and glycosaminoglycans extracted from granulomas and those synthesized and secreted by GR cells, suggesting that these cells may be the major cell population involved in synthesis and accumulation of these molecules in the schistosomal periovular granulomas in liver. Furthermore, we have shown that GR cells can function as an extramedullary myelopoietic stroma that mediates a long-term myeloid proliferation through an autocrine mechanism where the interaction between myelopoietic growth factors and cell-surface heparan sulfate proteoglycans was characterized. PMID- 7787810 TI - Integrin receptors and TGF-beta expression in chronic myeloid leukemia cells. AB - To understand the relationship between transforming growth factor beta-1 (TGF beta 1) and the integrin profile presented by chronic myeloid leukemia cells, we have studied, using Northern analysis, the expression of TGF-beta 1 messenger RNA (TGF-beta mRNA) in myeloid cell lines and in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition we determined the positivity for alpha 4 and alpha 5 integrin molecules in those cells using specific monoclonal antibodies and flow cytometry. CML patients (N = 3) presented mean values of alpha 4 and alpha 5 higher (alpha 4: 60 +/- 20%; alpha 5: 70 +/- 41%) than AML (N = 10) blast cells (alpha 4: 25 +/- 23%; alpha 5: 18 +/- 16%). Northern analysis revealed an almost four-fold higher expression of TGF-beta mRNA in K562 (derived from a patient with chronic myeloid leukemia) compared to the myeloblastic cell line HL60. The highest TGF-beta mRNA levels were seen in the U937 lineage. CML leukemic cells (N = 3) showed high TGF-beta mRNA levels comparable to the levels expressed by K562 which was paralleled by high beta 1 integrin mRNA. AML blast cells presented a variable degree of expression of TGF beta mRNA when compared to HL60. One patient with acute megakaryoblastic leukemia (FAB subtype M7), usually associated with myelofibrosis, presented the highest TGF-beta mRNA levels. We conclude that studying TGF-beta 1 and its mechanisms of action will help in understanding fibrosis in leukemic patients, and perhaps to design treatments for such conditions. PMID- 7787813 TI - Fibrosis patterns of lesions developed by athymic and euthymic mice infected with Paracoccidioides brasiliensis. AB - Athymic and euthymic mice with BALB/c background were used to study the patterns of fibrosis during ip infection with a virulent isolate of Paracoccidioides brasiliensis. Specimens from various organs were collected from the animals at 1, 4 and 7 weeks after infection and observed under light microscopy using various histologic staining methods. Lesions from the first week of infection, in both animal groups, presented a predominance of collagen III over I, carboxylated proteoglycans, and a tendency to encapsulation. From 4 weeks onward, the lesions of nu/+ mice tended to involute to macrophage-pseudoxanthomatous aggregates or to encapsulation with an increase of collagen I and sulfated proteoglycans. On the contrary, with the evolution of the infection, the nu/nu mice displayed permanently active lesions, rich in reticular fibers and carboxylated proteoglycans, with varied amounts of collagens III and I, without or with minimal encapsulation. However, independent of the type of mice, or of the type of lesions, the minimal P. brasiliensis-ECM unit was formed by a fibrillar cocoon of reticular fibers that encloses an individual yeast or a "family" composed of a mother cell plus one or various peripheral daughter cells, alone or engulfed by macrophages or giant cells. The overall difference of the lesions of nude and normal mice was not in isolated aspects of their components, but in the general architecture of the lesions. Those of nu/+ mice were either of involutive or of encapsulated type (slightly active), and those of nu/nu mice were of the sustained-expansive type (very active), without or with minimal encapsulation. PMID- 7787814 TI - Characterization of glycoprotein gp43, the major laminin-binding protein of Paracoccidioides brasiliensis. AB - We have demonstrated that laminin mediates the adhesion of P. brasiliensis to monolayers of epithelial cells through specific binding to the surface glycoprotein gp43. This binding seems to be related to the fungal pathogenesis. We now report the confirmation of these findings by scanning electron microscopy and show that some isolates that do not secrete gp43 do express the protein as seen by studying whole cell extracts. These results confirm the ability of these strains to produce paracoccidioidomycosis but should not be used for serological purposes since the absence of gp43 in exoantigens may lead to false negative results. PMID- 7787815 TI - Trypanosoma cruzi binds to laminin in a carbohydrate-independent way. AB - The binding of 125I-laminin to trypomastigotes is specific and 2-5 x 10(3) laminin-binding sites were calculated to be present on the surface of a live trypomastigote. Anti-laminin antibodies were able to inhibit the invasion of cultured cells by trypomastigotes (62-75%), suggesting that laminin may be involved in the adhesion of the parasite to host cells. By affinity chromatography, an 85-kDa glycoprotein was isolated (laminin-binding glycoprotein, LBG) from trypomastigote lysates, but not from epimastigote lysates. It is suggested that at least fragment E8 (but not E1') from laminin could be involved in the reaction which is independent of the carbohydrate moieties from both ligand and receptor. It is also shown that LBG is a member of the Tc-85 family, previously shown to be related to the invasion process of the parasite. PMID- 7787817 TI - Seroprevalence of hepatitis A antibodies in travellers at the Edmonton Travellers' Health Clinic--Alberta. PMID- 7787818 TI - Hepatitis A in downtown Montreal, Quebec, 1990-1992. PMID- 7787816 TI - 1995 Membership list. PMID- 7787819 TI - Cohort study of the relationship between air pollution and short term health effects as determined by peak expiratory flow measurements. AB - The aim of the study was to establish if air pollution has short term effects on health and well-being for individuals living in an industrialized area of Norway. A cohort study was designed so that two groups (one randomly selected from the general population and one with preexisting lung disease) were followed hour by hour during two months in the winter and in the summer of 1988. In order to minimize the problems of confounding factors, each individual served as her/his own control. Each participant described through the use of a diary the presence of symptoms from the upper and lower respiratory tract as well as general symptoms of ill health. Measurements of lung function by the use of peak expiratory flow meters were done four times a day. In addition, every second week the participants were subjected t a full spirometric test. Samples of urine and blood were examined, and bacteriological test from the throat was performed at the beginning and at the end of the study. A comprehensive measurement program of outdoor air contaminants (including nitrogen oxides, sulphur dioxide) is presented. Estimation of each participant's exposure was performed hour by hour based on detailed modelling of the measured levels, known emissions of pollutants and meteorological conditions, as well as diary information on the participant's movements through the various micro-environments. The estimated exposures were generally low. In this presentation, a linear regression model and their corresponding parameter estimates were applied on an individual basis to evaluate any effect of air contamination on lung function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787820 TI - Salmonellae in gulls and other free-living birds in the Czech Republic. AB - Cloacal swabs, collected from 756 wild synanthropic and exoanthropic birds of 57 species in the Czech Republic, yielded 32 strains of Salmonella typhimurium [phage types (PT) 141, 104 and 41], six isolates of S. enteritidis (PT 8, 4 and 6e), and one each of S. panama and S. anatum. Except for one S. enteritidis isolate from a grey-lag goose (Anser anser) and one S. typhimurium isolate from a coot (Fulica atra), all of the other strains were derived from black-headed gulls (Larus ridibundus), of which 24.7% were found to be infected. The black-headed gull might play a role in the dispersal of pathogenic salmonellae. PMID- 7787821 TI - Effect of stressful environmental factors upon neonatal immune system. AB - To examine the effects of stressful environmental conditions upon the immune system of the newborn (neonates), we analyzed the neonatal serum immunoglobulin levels in a total of 67 neonates from tribal families living in a rural community of eastern India. These cases were grouped into three categories, based upon the predominance of one of the three factors being analyzed, and the reasonable absence of the other two factors. The three factors as determined by the prevailing environmental conditions, which were the basis for forming the three groups, were: 1. indoor air pollution; 2. hygienic conditions, and 3. the cohabitation of domesticated animals in the same household as the infants's families. Presence of indoor air pollution or unhygienic conditions resulted in the disturbance and depression of the levels of serum immunoglobulins of different classes. There was no discernible correlation found between the levels of immunoglobulins of different classes from the neonates (except IgM) and the cohabitation of domesticated animals in the same households. However the incidence of GIT and RT infections was higher in all the three experimental groups, as compared to the control group. These results suggest that unfavorable environmental conditions can adversely affect the immune system at neonatal stages, and can increase their susceptibility to subsequent acute or chronic events. PMID- 7787822 TI - Industrialization and environmental health in Poland. AB - There has been enormous pollution and biodegradation of environment in Poland as the consequence of industrialization developed regardless the principles of sustainable development. In the recent years, the decrease of total emission of air pollution caused by gases and dust, the decrease of emission of unprocessed sewage and industrial waste can be seen. These facts are the consequences of economic recession which have appeared in Poland along with economic transformation. However, there is still significant escalation of environmental pollution, in so-called areas of ecological hazards. There are heavily industrialized and urbanized areas covering about 10% of the total country area but inhabited by over 30% of the total country population. The significant environmental pollution goes together with deterioration of the country's health situation what can be seen in shortening the average lifetime expectancy, increased frequency of cardiovascular diseases and cancers and higher infants death rate in comparison to other European countries. Considering the complexity of the factors affecting the population's health status, the basis of the health and environmental policy conceived in order to stop and alter the unwanted health condition tendencies and the environmental quality have been shown here. PMID- 7787823 TI - A resistance of head lice (Pediculus capitis) to permethrin in Czech Republic. AB - An outbreak of pediculosis at primary schools was recorded in the Czech Republic in 1992. Almost 20% of children in some schools were infested. This outbreak can be attributed to the resistance of head lice to permethrin, which has not been mentioned in literature yet. The resistance factors established in three towns range between 2 and 385 and between 5 and 557 for LC50 and LC90 values, respectively. This resistance has developed after exclusive use of pyrethroids lotion and shampoo in the Czech Republic since 1978, and it was accompanied by a cross-resistance to d-phenothrin and bioalethrin. But the susceptibility of head lice to malathion and pirimiphos-methyl in 1992 was very similar to that found in 1981. The lotion containing 0.3% of malathion (Diffusil H92 M) has been fully effective against the resistant lice. When introduced into the practice, it quickly reduced the infestation of children in primary schools. The other lotion and shampoo containing 0.3% and 0.7% of pirimiphos-methyl respectively were found to be effective as well. PMID- 7787824 TI - Natural foci of tick-borne encephalitis in central Europe and the relationship of the incidence of Ixodes ricinus to original ecosystems. AB - Based on reports of the national epidemiological service on tick-borne encephalitis (TBE) morbidity in 1953-1987, data in the literature, and results of the author's own field research on the occurrence of the common tick, Ixodes ricinus, foci of this disease have been identified on the territory of Czechoslovakia. In Bohemia a significant focus of TBE in the Central Bohemian Region is located in the Krivoklat area with forests and in the Berounka, mid Vltava, and lower-Sazava river basins, in the Brdy area and the Czech Karst continuing southwards via the Vltava basin to foci in the South Bohemian region in the districts of Pisek and Ceske Budejovice and west of the Berounka river basin to a focus in the central part of the West Bohemian region. In the North Bohemian and East Bohemian regions only smaller isolated foci of TBE were detected. In Moravia foci of TBE are in the districts of Opava and Bruntal in the North Moravian region and in the central and southern areas of the South Moravian region. The foci in Bohemia are isolated from foci in neighboring countries, those of Moravia are connected with foci in Poland and Austria. On the territory of the Czech Republic foci of TBE are found in localities of pristine oakwood agglomerations. Original beechwood agglomerations even when located below the upper limit of occurrence of the common tick, i.e. less than 700 meters above sea level, do not offer favourable conditions for this arthropod and they do not harbour natural foci of TBE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787825 TI - The prevalence of environmental mycobacteria in drinking water supply systems in Olomouc County, north Moravia, Czech Republic, in the period 1984-1989. AB - The presence of environmental mycobacteria was studied in drinking water supply systems in Olomouc County, Czech Republic, in order to detect the possible spread of M. kansasii from the neighbouring region in Ostrava County. Drinking water samples from water supply systems of 16 localities were investigated. The samples of running water, and tap swabs or tap scrapings were collected twice a year, in the spring and in the autumn. The most common cultivated and identified species were M. gordonae (20.4%), M. flavescens (13.8%), rapidly growing mycobacteria (5.0%) and then by occasional identification of M. fortuitum, M. terrae, M. scrofulaceum. M. kansasii was not detected. The prevalence rates showed no time trend over the period 1984-1989. We conclude that there is no evidence at present that endemic M. kansasii, isolated repeatedly from neighbouring region, has spread to Olomouc County. Different environmental and nutritional constituents in soil and coal mine dust in the endemic regions seem to be the most probable limiting environmental factor of the endemic occurrence of M. kansasii in its endemic locality in Ostrava and Karvina regions. PMID- 7787826 TI - Exposure and impact assessment of emissions from mercury recycling using domestic rabbits. AB - A biomonitoring study using domestic rabbits (Chinchilla) aimed at the exposure and impact risks assessment of emissions released into the ambient air from a mercury-recycling plant has been carried out. Groups of rabbits were exposed to the emissions during 6 months at biomonitoring stations built up in two localities (Rudnany and Matejovce) in the distance of about 3 and 6 km around and downwind from the mercury-producing plant. The aim of the biomonitoring was to trace the translocation of inhaled inorganic Hg in body tissues and the immunotoxic impact of the emissions in the exposed mammalian organism in comparison to a non-exposed animals living outside the polluted area. The content of mercury (as a major pollutant in the ambient air in that area) in body tissues was done spectrometrically using a Trace Mercury Analyser TMA-254. Content of mercury and the other metals in the rabbits' hairs was determined by neutron activation analysis. A statistically significant increase of the inorganic Hg content in the specimens of kidneys, lungs, liver, thigh bone, heart muscle and brain was observed. Concerning the hairs, a statistically significant elevation of Hg and other elements (As, Cd, La, Zn, Na, K, W, Sr) has been found. The body tissue reaction to the increased accumulation of mercury has been investigated by a direct immunofluorescent method to search for body tissue immune complexes. The significant increase of Hg content determined in the organs (especially in kidneys and liver) of the exposed animals was also traced by the presence of immunofluorescent antibodies. In addition, the immunofluorescent antibodies in the myocardium have been proved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787827 TI - Distribution and metabolism patterns of plasma 7S- and beta-NGF in the adult male rat. AB - There is a great deal of controversy on the existence of NGF in body fluids and tissues. To date it remains unknown whether this peptide accumulates preferentially at significant levels in different organs. Thus we undertook the evaluation of kinetic parameters of the disappearance of blood of 125I-7S-NGF and 125I-beta-NGF after intravenous injection in male adult rats. Our results indicate that the plasma half-life of 125I-7S-NGF is approximately twice as long as for 125I-beta-NGF (respectively 61.7 +/- 11.7 min and 36.3 +/- 2.2 min) while the distribution volume is not significantly different between both peptides. Furthermore, the uptake of radioactive NGF by different tissues seems very low as shown by 125I-7S-NGF and 125I-beta-NGF content of the sampled organs compared to the plasma concentration at the same time. These results indicate that the tissue uptake of circulating 7S and beta-NGF is very low in the adult rat. Thus in these animals NGF did not cross the blood-brain barrier and did not accumulate in peripheral organs which are known to contain subsequent amounts of this peptide. This lack of deposition might be due to a binding with plasma proteins (probably alpha 2-macroglobulin). PMID- 7787828 TI - A behavioral and electrophysiological study of the comparison of size-discrepant shapes. AB - An experiment was performed to find an electrophysiological correlate of the way objects of different sizes are perceived as identically shaped. The subjects were presented with pairs of geometrical figures and were instructed to decide whether the two polygons of a pair were identical in shape regardless of size. In addition to event-related potentials (ERPs), reaction times and error rates were recorded. Reaction times increased approximately linearly with increasing size ratios. The subtraction between the ERPs of 'test' and 'control' conditions showed two main activities: a positivity localized on the occipitotemporal scalp areas in the 200-450 ms range, and a negativity localized on the posterior scalp areas in the 500-750 ms range. These different results were discussed with respect to size ratio. PMID- 7787829 TI - Neural network models of cortical functions based on the computational properties of the cerebral cortex. AB - We describe a biologically plausible modelling framework based on the architectural and processing characteristics of the cerebral cortex. Its key feature is a multicellular processing unit (cortical column) reflecting the modular nature of cortical organization and function. In this framework, we describe a neural network model organization and function. In this framework, we describe a neural network model of the neuronal circuits of the cerebral cortex that learn different functions associated with different parts of the cortex: 1) visual integration for invariant pattern recognition, performed by a cooperation between temporal and parietal areas; 2) visual-to-motor transformation for 3D arm reaching movements, performed by parietal and motor areas; and 3) temporal integration and storage of sensorimotor programs, performed by networks linking the prefrontal cortex to associative sensory and motor areas. The architecture of the network is inspired from the features of the architecture of cortical pathways involved in these functions. We propose two rules which describe neural processing and plasticity in the network. The first rule (adaptive tuning if gating) is an analog of operant conditioning and permits to learn to anticipate an action. The second rule (adaptive timing) is based on a bistable state of activity and permits to learn temporally separate events forming a behavioral sequence. PMID- 7787830 TI - Estrogen-receptor occurrence in the female mouse brain: effects of maternal experience, ovariectomy, estrogen and anosmia. AB - Maternal behavior (ultrasound-induced pup-searching and retrieving) was studied in eight groups of female house mice with various hormonal backgrounds, experience with pups and function of the olfactory system. In their brains, estrogen receptor immunoreactive (ER-IR) cells were localized and quantified. All animals of all groups had ER-IR cells in a 'reliable subset' of brain areas, the medial preoptic area (MPOA) and ventromedial (VMH) and arcuate nucleus (ARH) of the hypothalamus. In another subset of brain areas, the anterior hypothalamic area (AHA) and cortical (CA) and medial (MA) amygdaloid nucleus, ER-IR cells can be expected in at least some animals of all experimental groups ('expected subset'). In a variable subset of additional brain areas (bed nucleus of the stria terminalis, BNST; suprachiasmatic nucleus, SC; lateral septal nuclei, LS; paraventricular nucleus of the hypothalamus, PVH; entorhinal and piriform cortex, ENT, PIR; subiculum, SUB; hippocampus, HPC; periventricular gray of the midbrain, PVG), ER-IR cells occurred only in some animals of some groups. Numbers of ER-IR cells in a given brain area, volumes occupied by these cells, and cell densities varied considerably among the groups. A covariation of cell counts and volumes was significant for most brain areas indicating that increases of numbers of ER IR cells relate mainly to volume increases within a given brain area. Experience with pups correlated with an increase of ER presence in the AHA, VMH, ENT, PIR, SUB, HPC and PVG, however, only in the presence of estrogen. Estrogen and pup experience together led to an increased ER presence in mainly the VMH, ENT and PIR, however, only in females with intact olfaction. Full maternal behavior (retrieving, ultrasound recognition) occurred after the high pregnancy- or experience-induced ER content was reduced to lower levels. The ER occurrence in lactating and experienced virgin females differed, however, in the AHA, BNST, SC, PVH, ENT, PIR, SUB, HPC and PVG showing that the maintenance of maternal behavior can run under different profiles of ER content in the brain. Ovariectomy and/or prolonged high blood-estrogen levels correlated significantly with decreased levels of ER-IR cells in most brain areas which could not be increased by pup experience. PMID- 7787832 TI - Cognitive moderators of outcome following traumatic brain injury: a conceptual model and implications for rehabilitation. AB - This paper presents a conceptual model describing the relationships between quality of life outcomes following traumatic brain injury (TBI), coping patterns, and beliefs regarding self-efficacy to assist health-care professionals in understanding the complexity of social and psychological sequelae of TBI. The mode hypothesizes that long-lasting cognitive, behavioural, emotional psychiatric, and interpersonal after-effects of TBI may create a real life 'learned helplessness' with consequent deficits in coping, and altered locus of control beliefs. As a result, TBI patients are at risk for developing self limiting belief systems about their effectiveness in altering significant events that may result in over-generalizing the effects that TBI has in their day-to-day lives. Subsequently, a feedback loop may be set up where their beliefs in not being able to influence outcomes are not tested, life chances are further restricted, outcomes are suboptimal, and quality of life is reduced. The clinical and theoretical implications of this model are discussed, and an expanded model with future research directions is suggested. PMID- 7787831 TI - D1 receptors modulate striatal dopamine release induced by the stimulation of both D1 and D2 receptors: in vivo voltammetric data revisited. AB - Here we re-examine previous data that demonstrated lasting effects of the selective D1 receptor agonist SKF 38393, the selective D2 receptor agonist LY 171555, and of mixed SKF 39383 + LY 171555 upon striatal DA release. We demonstrate that the administration of mixed SKF 38393 + LY 171555 and of SKF 38393 administered alone induced similar time-course effects upon striatal DA release that showed significant parallel developments. We discuss these data in the light of the current literature and we suggest that D1 receptors could play a modulating role on the striatal DA activity and the release of DA in the caudate putamen. PMID- 7787833 TI - Self-concept, marital vulnerability and brain damage. AB - The present study investigated the influence of a man's brain injury on both his and his wife's self-concept and perception of marital vulnerability. Thirty-six couples in which the husbands had brain damage and twenty-nine couples without disability filled out the Tennessee Self-concept Scale [1], and the Marital Vulnerability Scale [2]. Marital vulnerability of husbands with brain damage was found not to differ from that of the husbands in the control group. However, the marital vulnerability of the wives of the former husbands was lower than that of the other wives. Both men with brain damage and their wives exhibited a decrease in self-esteem and an increase in conflict and pathology. Brain damage appears to affect both the extent and direction of the relations between aspects of the self concept and marital vulnerability differentially for husbands with brain damage and their wives. Practical and theoretical implications of the negative impact of brain damage upon the person with the damage, upon his wife, and upon their marital relationship are discussed. PMID- 7787835 TI - Perseveration. Part I: a review. AB - Perseveration refers to the inappropriate continuation or repetition of a response or activity. It is associated with a variety of neurological disorders and, when pronounced, is thought to be pathognomonic of brain damage. Perseveration manifests itself in several different forms which have had various labels applied, and many hypotheses have been proposed to explain the mechanisms underlying these perseverative behaviours. In this article we review descriptions and classifications of perseveration as it occurs in various neurological disorders, and then discuss some of the neurobehavioural and neuropathological mechanisms thought to account for it. PMID- 7787834 TI - Self-reported social networks and interpersonal support 2 years after severe traumatic brain injury. AB - Fifty-four patients with traumatic brain injury (TBI) consecutively admitted to a rehabilitation hospital were examined 2 years post-injury. Social interaction and support, subjective complaints, and functional status were assessed. A large variability in social interaction and support patterns was found. Most patients had more interaction and received more support from family members than from friends and neighbours. Thirty-one patients (57.4%) reported that their social networks had markedly declined subsequent to injury. Relatively short duration of coma (< 1 week) and severe sequelae in terms of low functional status and poor emotional adjustment at follow-up, especially in terms of deficits in initiating behaviour, were found to be related to little interaction and support. The importance of both provider and patient initiative in order to establish and preserve a social support network is suggested, and clinical implications briefly discussed. PMID- 7787836 TI - Perseveration. Part II: A study of perseveration in closed-head injury. AB - This study examines the nature and extent of perseveration in 15 individuals with closed-head injury (CHI) by (a) identifying and describing the types of perseveration that occurred on verbal and non-verbal tasks, (b) examining the possible underlying neuropsychological mechanisms of perseverative behaviour and (c) exploring neuroanatomical correlates of perseveration. Performance of the 15 CHI patients was compared with 15 neurologically normal subjects matched for sex, age, handedness and educational level. The CHI subjects produced significantly more perseverations than did normals, and 'recurrent' perseveration was the most frequently occurring type. A test of verbal learning elicited the greatest number of recurrent perseverations. Overall test performance of the CHI group suggested that memory dysfunction and impaired attention were most likely responsible for perseverative errors. CT scan analyses showed that the three most perseverative CHI subjects evidenced left temporal lobe damage. PMID- 7787837 TI - Developmental models of social cognition in assessing the role of family stress in relatives' predictions following traumatic brain injury. AB - The present study extended the utilization of developmental models of social cognition to the investigation of stress and relatives' perception of traumatic brain injury (TBI) survivors. Structured interviews were conducted with 21 TBI survivors utilizing interpersonal negotiation strategies (INS) and self understanding (self) in the framework of Selman's model of social perspective taking and Damon and Hart's multidimensional model of self understanding. A relative group composed of 21 participants was interviewed and their predictions of the responses of the TBI survivors to the action domain of the INS stories were obtained. The relative participant group was also administered the Beck Anxiety and Depression Inventories and Leeds Scales of Depression and Anxiety. The relationships among relative groups' predictive scores, INS and self domains and stress levels were analysed. The result of the survivor groups responses on INS and self were in agreement with the previous findings that TBI survivors respond at psychosocially immature levels. Comparison of INS action scores obtained by the survivor group and predicted by relative group were within one developmental level of each other in 87.4% of the cases. Fifty-two per cent of the relative group scored in mild to moderate or greater depression and 48% scored in the mild to moderate range of anxiety on the Beck scales. Person correlation coefficients indicated significant negative correlations between Beck scores and predictive INS scores. ANOVA indicated significantly higher Beck depression scores in relatives of TBI survivors living in residential facilities than relatives of TBI survivors in an outpatient treatment programme. The study supports the view that developmental social cognition methods appear to advance our understanding of psychosocial adjustments and relatives' perceptions of social cognition in TBI survivors. PMID- 7787838 TI - Head injuries in the elderly. AB - Two hundred and sixty-three consecutive head-injured patients aged over 65 years, admitted to a neurosurgical service, are reported. In contrast to younger age group the main cause was falls concomitant with a high rate of cardiovascular pre existing disorders. The distribution of causes and grim results justify, in our opinion, regarding head injury in the elderly as a distinct entity requiring special surgical, medical, organizational and ethical considerations. PMID- 7787839 TI - Subpopulations in closed-head injury: preliminary results. AB - The classification systems currently utilized to categorize closed-head injury (CHI) patients are all based on severity levels. However, these scales are unable to account for the wide variability among CHI patients. Another way to classify these patients is to use the clinical picture independent of the overall severity level. That approach is used with aphasic patients but not with the CHI population. These preliminary data indicate that there are distinct subgroups in the CHI population. These subgroups can be identified by their overall pattern of performance on a battery of tests covering language, memory, visuospatial, cognitive and discourse skills. The characteristics of the tentative subgroups are described, but a more extensive study is needed to confirm the robustness of this classification. PMID- 7787841 TI - Synthetic pheromone biosynthesis activating neuropeptide gene expressed in a baculovirus expression system. AB - A synthetic gene of the pheromone biosynthesis activating neuropeptide (PBAN) of corn earworm Helicoverpa zea, with and without a signal sequence of the cuticle protein of Drosophila melanogaster, was cloned behind the polyhedrin promoter of AcMNPV. Two recombinant baculoviruses were constructed and used to infect a number of insect cell lines including Sf9 and 5B1-4. High pheromonotropic activity was consistently obtained from 5B1-4 cell culture that was infected with the recombinant baculovirus vINV-4 containing the signal sequence. The PBAN gene product was isolated by HPLC and analyzed by electrospray ionization mass spectrometry. Low levels of biological activity obtained from Sf9 cells infected with the recombinant virus vPBAN may be due to lack of proper amidation at the C terminus of the expressed peptide or rapid proteolytic degradation of the product. PMID- 7787840 TI - Biotin-containing proteins of the insect nervous system, a potential source of interference with immunocytochemical localization procedures. AB - When the biotinylated Manduca sexta adipokinetic hormone gene was used as a probe for in situ hybridization, the intrinsic neurosecretory cells were stained with a biotin detection system that contained streptavidin or avidin. Further experiments showed that the DNA probe was not necessary for staining these cells by streptavidin-alkaline phosphatase, and that they were not stained by alkaline phosphatase alone. Similarly, the intrinsic neurosecretory cells were stained directly by streptavidin conjugated to a fluorescent dye. Other parts of the central nervous system could also be stained with streptavidin-alkaline phosphatase but not as readily as the intrinsic neurosecretory cells of the corpora cardiaca. Further analysis demonstrated three biotin-containing proteins in the intrinsic neurosecretory cells of the corpora cardiaca and in the brain. The most abundant of these proteins, when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was found to have a molecular weight of 130,000, which is the size of the subunits of pyruvate carboxylase, a biotin containing enzyme. The same protein was recognized by an antiserum against an insect pyruvate carboxylase, indicating that this protein is probably pyruvate carboxylase. The results reported here indicate that the intrinsic neurosecretory cells of the corpora cardiaca may contain pyruvate carboxylase in a concentration higher that other cells of the central nervous system. We also note that caution is necessary to avoid false positive results if an avidin containing detection system is used for in situ hybridization or immunocytochemistry. PMID- 7787842 TI - Multiple phosphorylation of ribosomal protein S6 and specific protein synthesis are required for prothoracicotropic hormone-stimulated ecdysteroid biosynthesis in the prothoracic glands of Manduca sexta. AB - Prothoracicotropic hormone (PTTH)-stimulated protein phosphorylation leads to ecdysteroidogenesis (molting hormone biosynthesis) in the prothoracic glands of the tobacco hornworm, Manduca sexta. The phosphorylation of 34 and 50 kDa peptides (p34 and p50) paralleled the increase in ecdysteroidogenesis, and the dephosphorylation of p34 and p50 preceded a decrease in ecdysteroidogenesis. Inhibition by rapamycin of p34, but not p50, phosphorylation prevented PTTH stimulated ecdysteroidogenesis in a dose-dependent manner, suggesting that p34 phosphorylation is requisite for PTTH-stimulated ecdysteroidogenesis. Two proteins whose synthesis was rapidly stimulated by PTTH were p50 and p70. The time-course of PTTH-stimulated synthesis of p50 paralleled that of p34 phosphorylation and that of ecdysteroidogenesis. Rapamycin inhibited PTTH stimulated synthesis of p50 and p70, suggesting that specific protein synthesis is also required for PTTH-stimulated ecdysteroidogenesis, confirming the results of Rybczynski and Gilbert [(1994) Insect Biochem. Molec. Biol. 24, 175-189], and that p34 phosphorylation may regulate the downstream synthesis of p50 and p70, possible key regulatory proteins leading to ecdysteroidogenesis. Results from two dimensional (2D)-PAGE analysis of the ribosomal proteins purified from prothoracic glands, demonstrated that p34 is indeed ribosomal S6, and is phosphorylated at up to five sites (P1-5) upon PTTH stimulation. The multiple phosphorylation of S6 was inhibited completely by rapamycin as shown in 2D gel maps, further confirming that p34 is ribosomal protein S6. Temporal analysis of PTTH-stimulated S6 phosphorylation by 2D-PAGE revealed that phosphorylation of S6 at the P1 site was temporally correlated with the initiation of ecdysteroidogenesis, and that multiple phosphorylation at all five sites (P1-5) was correlated with the maximal synthesis of ecdysteroids. Dephosphorylation of S6 was accompanied by a decrease in ecdysteroidogenesis. These data demonstrate that p34 is ribosomal protein S6 and that both the phosphorylation of S6 and specific protein synthesis are required for PTTH-stimulated ecdysteroidogenesis in the prothoracic gland. PMID- 7787845 TI - Microsomal juvenile hormone binding proteins in the follicle cells of Tenebrio molitor. AB - The microsomal fraction of Tenebrio molitor follicle cells has been found to contain both high and low affinity binding sites for juvenile hormone (JH) III. Using Scatchard analysis, the equilibrium dissociation constants, Kd, were calculated as 1.0 x 10(-8) and 4.3 x 10(-7) M respectively. Kinetic data support a rapid binding of the hormone to the site(s), with rate constants of ka = 3.77 x 10(8) M-1 min-1 and kd = 0.0075 min-1. Affinity of the binding site(s) for JH III was higher than for either JH I or methoprene. The significance and possible function of such microsomal binding proteins are discussed, with reference to the perturbance of vitellogenesis found in beetles parasitized by Hymenolepis diminuta. PMID- 7787844 TI - Characterization of a salivary gland-specific esterase in the vector mosquito, Aedes aegypti. AB - Esterase enzymatic activity was investigated in salivary gland lysates of adult Aedes aegypti. Esterases in lysates made from female glands had higher specific activity than those in lysates from male glands towards beta-naphthyl acetate but showed no difference with alpha-naphthyl butyrate as a substrate. Female salivary gland lysates showed no difference in activity to alpha- and beta-forms of naphthyl acetate and no discernable activity towards alpha-naphthyl caprate. Both female and male salivary gland lysates exhibited phosphatase enzymatic activity but the specific activities were lower than those seen for the esterase enzymatic activity. Salivary gland esterase activity was inhibited completely by paraoxon, para-hydroxymercurobenzoate, tetraethylammonium iodide and moderately by diisopropylfluorophosphate. Eserine and phenylmethylsulfonylfluoride had no effect on enzyme activity. In a probing assay, adults of both sexes were shown to secrete esterase in saliva. Esterase activity was present in the saliva of females probing for either a sugar meal or a blood meal. Furthermore, esterase was secreted from female salivary glands in culture. Histochemical analysis of dissected salivary glands showed that the majority of the esterase enzymatic activity was in the distal-lateral lobes of the female tissues, although the proximal-lateral and medial lobes also had activity. Male salivary glands stained uniformly over all of the lobes. A salivary gland-specific esterase, designated SG-EST, appears to account for the majority of enzyme activity in the glands. SG EST was partially purified by electroelution of an active protein from native polyacrylamide gels, and has an approximate molecular weight of 65,000 Da. In separate experiments, affinity chromatography independently identified a single 65,000 Da protein likely to be SG-EST. Native electrophoretic analysis of salivary glands revealed that, while most enzyme activity is due to SG-EST, there are two other esterases present. One of these minor moieties is present in adult tissues in addition to the salivary gland, and the other is present throughout development. Possible functions of the salivary gland esterase are discussed. PMID- 7787843 TI - Characterization of Aphidius ervi (Hymenoptera, Braconidae) ribosomal genes and identification of site-specific insertion elements belonging to the non-LTR retrotransposon family. AB - We performed a molecular analysis of the Aphidius ervi ribosomal gene structure. This insect belongs to a set of closely related Aphidiinae species of the genus Aphidius Nees, of relevant interest in biological control. We constructed A. ervi genomic libraries, cloned and characterized several rDNA repeating units and sequenced different regions of the rDNA cistrons. We have found that insertion sequences interrupt the A. ervi 28S rDNA genes: the sequences of the two 5' and 3' insertion-28S junctions show that the elements are present at the position where R1 elements have been found in various insect species. In addition, the insertion of the element produces a duplication of the 14 nt target region. The sequence analysis indicates that the A. ervi elements belong to the R1 retrotransposon family with a highly conserved reverse transcriptase domain. PMID- 7787846 TI - Phylogenetic position of yeast-like symbiotes of rice planthoppers based on partial 18S rDNA sequences. AB - The rice planthoppers, Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus, harbor intracellular yeast-like symbiotes (YLS) in the fat body. The YLS are obligated endosymbiotes and are transovarially inherited. Nucleotide sequences of the 18S rRNA genes from the YLS were analyzed by direct sequencing. The YLS of the three species of planthoppers were monophyletic and their taxonomic positions were in the class Pyrenomycetes in the subphylum Ascomycotina. PMID- 7787847 TI - A Drosophila gene that encodes a member of the protein disulfide isomerase/phospholipase C-alpha family. AB - Screening of a Drosophila genomic DNA library at reduced stringency hybridization conditions using a rat PLC alpha cDNA probe yielded a gene which encodes a member of the protein disulfide isomerase/PLC alpha family. The gene has been localized to band 74C on the left arm of the third chromosome and has been designated dpdi. Northern analysis shows that the dpdi gene encodes a transcript that is 2.3 kb in length and is present throughout development as well as in both heads and bodies of adults. The deduced dpdi protein is 496 amino acids in length and contains two domains exhibiting high similarity to thioredoxin, two regions that are similar to the hormone binding domain of human estrogen receptor, and a sequence of four amino acids (KDEL) at the C-terminus which has been described by others as being responsible for retention of proteins in the endoplasmic reticulum. Overall, dpdi contains a higher similarity to rat protein disulfide isomerase (53% identical) than to rat PLC alpha (30% identical). However, it is unclear whether dpdi functions in vivo as a PDI or as a PLC, or both. Drosophila, with its well characterized genetics and the ability to generate mutants in a gene that has been cloned, provides an excellent system in which to resolve this issue. PMID- 7787848 TI - Proximal tibiofibular subluxation relationship to lateral knee pain: a review of proximal tibiofibular joint pathologies. AB - Proximal tibiofibular subluxation is the symptomatic hypermobility of the proximal tibiofibular joint. Pain along the lateral aspect of the knee must be carefully evaluated as the anatomy and biomechanics of this region are very complex. Anatomical variants of the proximal tibiofibular joint may be key to understanding the pathomechanics and, thus, treatment of this joint. The "horizontal" proximal tibiofibular joint has a higher degree of mobility, while the "oblique" joint is relatively immobile to rotational forces on the fibula. Increased fibular external rotation will result in injury to the anterior capsule and ligaments of the proximal tibiofibular joint causing common complaints of "popping" and lateral knee pain. Treatment of proximal tibiofibular subluxation will involve modifications of a patient's activity level and training programs, utilization of a supportive strap, lower leg strengthening, and modifications in the lower kinetic chain biomechanics. PMID- 7787849 TI - The effect of two types of foot orthoses on rearfoot mechanics. AB - Little experimental data exist regarding the comparative biomechanical of various foot orthoses. This study evaluated the comparative effect of biomechanical orthoses and over-the-counter arch supports on controlling rearfoot pronation. Twenty-four patients with forefoot varus deformity were studied while walking on a treadmill. Two-dimensional, videotape motion analysis was used for studying rearfoot mechanics with three experimental conditions: 1) shoes only, 2) shoes plus arch supports, and 3) shoes plus biomechanical orthoses. The variables studied were: maximum pronation, calcaneal eversion, maximum pronation velocity, time-to-maximum pronation, and total pronation. No difference was noted in maximum pronation, calcaneal eversion, and total pronation between the three conditions. The data for maximum pronation velocity and time-to-maximum pronation were not reliable. Based on the results of this study, padded arch supports nor biomechanical orthoses can be preferentially recommended for their ability to control maximum pronation, calcaneal eversion, and total pronation during walking. Additional research is necessary to: 1) identify the biomechanical effects that are responsible for the clinical success of foot orthoses, and 2) determine better designs for controlling rearfoot movement. PMID- 7787851 TI - Patellofemoral joint compressive forces in forward and backward running. AB - The use of backward running is becoming more common in the rehabilitation setting. In particular, backward running has been suggested as a treatment modality in patients experiencing patellofemoral pain syndrome. To date, no study has examined the loads at the patellofemoral joint during backward running. The purpose of this study was to compare patellofemoral joint compressive forces during forward and backward running. Ground reaction force and kinematic data were collected on five male joggers during free speed forward and backward running. A floor reaction force vector model was used to calculate the stance phase knee extension moments. The distance used for the extensor muscle lever arm was 4.9 cm. Patellar mechanism angle was calculated based on knee joint angle. There was a reduction in the peak patellofemoral joint compressive forces in backward compared with forward running (2277 +/- 192N vs. 4253 +/- 1292N; p < 0.05) at self-selected speeds. Peak patellofemoral joint compressive force occurred significantly later (p < 0.05) in the stance phase of backward running (52 +/- 4%) than in forward running (35 +/- 3%). The peak patellofemoral joint compressive force normalized to subject body weight was 5.6 +/- 1.3 body weight in forward running and 3.0 +/- 0.6 body weight in backward running. The results suggest that backward running at a self-selected speed may reduce patellofemoral joint compressive forces and, coupled with the quadriceps strengthening that has previously been reported, may be beneficial in the rehabilitation of patellofemoral pain syndrome in runners. However, constant speed comparisons or other models may yield different results. PMID- 7787852 TI - The effects of therapeutic application of heat or cold followed by static stretch on hamstring muscle length. AB - Hamstring stretching is an important part of treatment programs aimed at decreasing the likelihood of hamstring injury. Few studies have examined the use of superficial thermal modalities in conjunction with hamstring stretching. The purpose of this study was to determine if the application of a superficial heating or cooling modality, followed by static stretch, increased the efficacy of static stretching of the hamstring muscles. This study examined 12 male and 12 female subjects, ages 18-38. All subjects received each of the following treatments: heat followed by static stretch, cold followed by static stretch, and static stretch alone. Each treatment was separated by at least 1 week. Pre- and post-treatment measurements of hamstring length were obtained using the Active Knee-Extension (AKE) test. The data were analyzed via a 2 x 3 analysis of variance experimental design. Results indicated that there was an increase in hamstring length regardless of stretch treatment used, with F(1,23) = 35.49, p < .001. However, no significant differences were detected among stretch treatments, F < 1.0, nor among interaction effects, F < 1.0. The results of this study suggest that adequate hamstring stretching can occur without the use of a superficial thermal modality. PMID- 7787853 TI - Posture in patients with shoulder overuse injuries and healthy individuals. AB - Assessment of posture is an integral component of patient evaluation with shoulder overuse injuries. However, the professional literature contains relatively few studies that have assessed the relationship between posture, function, and injury. The purpose of this study was to determine the relationship and differences in postural variables within and between subjects with overuse injuries to the shoulder of healthy subjects. Thirty patient subjects and 30 healthy subjects matched for age and gender were recruited. Scapular protraction and rotation, forward head position, midthoracic curvature, and passive humeral elevation in the plane of the scapula were measured randomly in standing. All measurement techniques were standardized and validated. Intrarater and interrater reliability for all clinical measures were established before data collection. Forward head position was significantly greater (p < .001) in the patient group than the healthy group; humeral elevation was significantly greater (p < .001) in the healthy group than in the patient group and in the uninvolved shoulders (p < .01) than the involved shoulders within the patient group. Scapular protraction, rotation, midthoracic curvature, and scapular symmetry were not significantly different between groups. Scapula protraction and rotation were significantly related (p < .05) in the patient group. No other postural variables were related. Conclusions regarding the influence of posture to shoulder injury are inconclusive based on several confounding variables that may have affected the outcome. PMID- 7787850 TI - Energy expenditure of below-knee amputees during harness-supported treadmill ambulation. AB - Traditional rehabilitation of amputees is primarily aimed at strengthening remaining musculature necessary for prosthetic use and gait training. Available gait training time, however, is often limited by pain, residual limb skin tolerance, and the patient's cardiovascular endurance. Harness-supported treadmill ambulation is a rehabilitation technique being used by physical therapists to decrease an individual's body weight by a given percentage during exercise. This, theoretically, allows an amputee to ambulate on a prosthesis at a lower energy cost. The purpose of this study was to compare the energy expenditure of healthy below-knee amputee volunteers with healthy able-bodied volunteers during harness-supported treadmill ambulation in order to determine if energy conservation is achieved. Subjects were tested on a treadmill, walking at .67 m/sec (1.5 mph) and 1.34 m/sec (3.0 mph) during each of the following randomized harness-supported treadmill ambulation situations: full body weight, 20% body weight supported, and 40% body weight supported. During the last minute of each trial, rate of perceived exertion, heart rate, and standardized indirect calorimetry oxygen consumption (VO2, ml/kg/min) measures were collected. Caloric expenditure (kl/min) was calculated using metabolic conversion equations. Peak heart rate, peak VO2, and peak kl/min were measured after the conclusion of the last walking trial by taking each subject to volitional fatigue. Data were analyzed for each harness-supported treadmill ambulation situation and group using analysis of variance (ANOVA). The researchers identified significantly lower ratings of perceived exertion, heart rates, and VO2s for able-bodied subjects vs. below-knee amputees for all trials. Both groups demonstrated significantly lower heart rates, VO2s, and kl/min at 1.34 m/sec with 40% body weight supported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787854 TI - [Our experience with the orthotopic continent colonic neobladder]. AB - In the last years particular surgery operations became refined for the techniques and therapeutics progresses also developed in this field. This has allowed with major security to accomplish engagemently reconstruction operations after removal of the bladder, especially for cases of neoplastic pathology, to offer the patients a more normal quality of life avoiding urinary derivations that should change the performance of "EGO". After the operations of radical cystoprostatovesciculectomy different methods have been presented for the construction of heterotopical and orthotopical neobladder; among these the continent colic orthotopical neovesica of Goldwassern which uses the detubulization right colon, in our opinion could offer best functional and clinic results in virtue of easier execution and to use of minor number of intestinal segments. Moreover, for the peculiar characteristics of colic segment, allow to make a wide tank at low pression with perfect diurnal and nocturnal continence. We have, therefore, presenting the results of our experience regarding 12 cases of continent colic orthotopical neovesica, by Goldwasser, with a follow-up of 1-6 years which have comforted us with the results predicted. Although other techniques may offer similar results we believe that the Goldwasser method is still valid for all the above reasons. PMID- 7787855 TI - [Abnormal production of oxygen free radicals by low leukocytospermia in purified fractions of semen from infertile patients]. AB - Seminal leucocytes (WBC) play an important role, whereas this is still unknown. Quantitative normal threshold-value for leucocytospermia (Ls) (WBC < or = 1 million/ml) seems not to be a safety predictive marker of male accessory gland infection (MAGI) and/or MAGI-related adverse effects on semen quality and/or fertility because several drawbacks: a) inadequate staining techniques are responsible of an underestimated WBC concentration in spermatic fractions (100%) obtained from high-density Percoli gradient (Pc 100%); b) Ls could be correlated far better to the clinical findings and/or outcomes if some biochemical data on L metabolism are also studied (Radical Oxygen Species-ROS-generation, phagocytosis, leucotoxins). In order to point out importance about an joint morphological/biochemical analysis about Ls, we recruited 76 selected infertile (from 2-7 yrs) patients (aged 32-45 yrs) who, in their 50% Percoli fractions, had previously produced WBC-ROS > 95th percentile values registered from our control group (n = 28, fertile men). In all infertile population we have analysed through Pc100 fraction either the percentage of WBC-negative patient's specimens (group A) and within WBC-positive ones if a significant difference was present in the maximal WBC-ROS production among different subgroups at WBC concentrations (group B:0.01-0.09, group C:1-10, group D: > 10 x 10(4) WBC/10(7) spermatozoa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787856 TI - [Lymphocyte levels before treatment with subcutaneous interleukin-2 and during maintenance treatment in relation to the clinical efficacy in metastatic renal carcinoma]. AB - AIMS AND BACKGROUND: the antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patients who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: the study included 60 metastatic renal cell patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 17/60 patients, 23 patients a SD, and the remaining 20 cases progressed. Non-progressed patients (n = 40) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 29/40 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocytes, NK cell number determination and sCD25 level detection. RESULTS: the mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL 2 chronic therapy. PMID- 7787857 TI - [Prognostic predictive factors of the clinical response to immunotherapy with subcutaneous interleukin-2, in patients with metastatic renal carcinoma: analysis of 60 cases]. AB - The intravenous immunotherapy with high-dose interleukin-2 (IL-2) would constitute one of the most effective treatments of metastatic renal cell carcinoma (RCC). More recently, IL-2 subcutaneous therapy has also appeared active, either alone or in association with interferon, with results comparable to those found with the intravenous route of injection, but with a lower toxicity. On this basis, we have designed a protocol of treatment with low-dose IL-2 alone given subcutaneously as a first or a second line therapy in metastatic RCC. The study included 60 consecutive patients (pts) (M/F: 39/21, median age 56 years, range 26/74). IL-2 was given at a dose of 3 millions IU twice/day for 5 days/week, for 6 weeks, corresponding to one cycle. In non progressed pts a second cycle was repeated after a 28-day rest period. Dominant metastasis sites were, as follows: soft tissues: 8; bone: 11; lung: 29; liver: 3; liver plus lung: 7; adrenal: 2. The minimum follow-up was 18 months and the median follow-up was 34 months (range 18-48). A complete response (CR) was achieved in 2/60 (3%) pts. A partial response (PR) was obtained in 15/60 (25%). Therefore, tumor objective rate (CR + PR) was 17/60 (28%). The median duration of response was 13 months (4 33).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787859 TI - [Correlation between ultrasonography imaging and surgical findings in scrotal trauma]. AB - The Authors report their experience of 20 cases of scrotal trauma. The etiopathogenesis of lesions are stressed as well as the importance of an early diagnosis, in order to plan a correct treatment avoiding immunological and atrophic outcomes. All of the patients underwent a diagnostic ultrasonographic examination. Eighteen of them were surgically treated, whereas last two recovered by means of a week antibiotic and anti-inflammatory medical therapy. The scrotal sonography showed a 100% sensibility for testis injuries and a 80% specificity for albuginea fractures. In fact a fracture of the tunica albuginea was found in two cases although they showed a normal scrotal sonogram. It is worth of mention that in the authors' experience the ultrasonography generally understages the testis damages. Only the surgical exploration is believed to be able to make a sure diagnosis of type and seriousness of the scrotal injury. PMID- 7787858 TI - [Bladder hernia: a clinical case]. AB - The Authors report a case of inguinal bladder hernia and briefly refer about the different kinds of this rare pathology which is often associated to the commonest inguinal hernia. They, moreover, point out the surgical treatment which has to aim to the repositioning of the bladder and to solve the cervicovesical obstruction. PMID- 7787860 TI - [Transrectal echography in laser treatment of incidental prostatic carcinoma]. AB - This report is concerning on our experience in the management of the incidental prostatic cancer treated by laser irradiation and transrectal ultrasounds (TRUS). 22 patients, with stage A incidental prostatic cancer, underwent preliminary TRUS to evaluate suspected areas of residual tumor and/or the capsule thickness. 5 patients, before the laser irradiation, have been treated with 2nd look TURP because residual tumor or much residual prostatic tissue was present. Following TRUS evaluation all the patients underwent a laser irradiation with TRUS guidance. During the laser irradiation TRUS evaluation allows to recognize the anatomy of the prostatic capsule, the thickness of the capsule and to perform a safety and complete laser irradiation of the prostatic capsule with a depth laser irradiation. In the postoperative follow-up the TRUS demonstrated, in 18 patients, a complete laser induced fibrosis of the capsule. In conclusion the TRUS represents a good technique for pre and postoperative evaluation in the patients of stage A prostatic cancer treated with laser irradiation. PMID- 7787861 TI - [Echo-guided percutaneous treatment of intraprostatic cysts]. AB - Diagnostic and therapeutic values regarding echoguided percutaneous treatment of intraprostatic cysts are reviewed and discussed. Since 1987 we have detected by ultrasonography 48 intraprostatic cysts, 22 asymptomatic patients were evaluated periodically. A ultrasound guided percutaneous puncture was performed in 26 symptomatic patients. 10 patients affected by dysuria were treated by aspiration and injection of antibiotics. 14 oligospermic patients underwent cyst aspiration followed by introduction of sclerosing agents (aethoxysclerol or alcohol). In one communicating cyst simple aspiration has been performed. A giant cystoadenoma has been resolved by surgical procedure. In the follow-up (2 months - 6 years) we observed: 5 recurrences (50%) in the cysts treated with antibiotics and 6 (43%) recurrences in the cysts treated with sclerosing agents. However, 8 patients out of 10 obtained a resolution of the urinary symptoms and 8 patients out of 14 improved their seminal parameters. On our experience, percutaneous echoguided treatment of prostatic cysts is a suitable and safe technique because of the possibility to resolve some clinic problems, although an high recurrence rate. PMID- 7787862 TI - [The acquitted obese]. PMID- 7787863 TI - [Protective effects of glutamine and elemental diet in acute actinic enterocolitis: histological evaluation]. AB - Radiotherapy plays nowadays an important role in malignancies treatment. However, collateral effects and severe complications owing to cellular damage of peritumoral tissues may occur. Different nutritional resources have been recently indicated to achieve intestinal protection during cancer irradiation. PURPOSE- The aim of this study was to set the role of glutamine and elemental diets in acute actinic enteritis prevention. METHOD--Sixty-five adult male Wistar rats with average weight of 200g were maintained in individual metabolic cages; daily body weight and food ingestion were carefully monitored. The animals were randomized into three groups and fed isocaloric and isonitrogenous diets: 1) CRt polymeric-casein diet; 2) GRt-polymeric-casein diet supplemented with 2% glutamine and 3) ERt-elemental diet supplemented with 2% glutamine. After an adaptation period (seven days), all rats received abdominal radiation in five daily doses of 300cGy. Four days after the rats were operated on to resect the small intestine and colon for histological evaluation. RESULTS--Small intestine histological data in ERt and GRt rats were better than CRt rats, by preserving mucosal cellularity and increasing mitosis number and villi length. Simultaneously, ERt group had greater number of rats with normal villus-crypt relation than CRt or GRt groups. Large intestine histological data showed that the average crypts length in ERt and GRt rats were greater than in CRt ones. CONCLUSION--Glutamine-supplemented polymeric or elemental diets given to rats before, during and after abdominal radiotherapy showed protective effects against radiation injury, by supporting mucosal structure and recovery. PMID- 7787864 TI - [Placenta: a barrier for renotrophic factor?]. AB - BACKGROUND: To evaluate if the renotrophic factor can pass through the placenta and act on the fetal kidney. MATERIAL AND METHODS: Twenty pregnant rats were divided into 4 groups of 5 animals: 1-control; 2-sham operated animals; 3-right nephfrectomy; 4-right nephrectomy--left polar nephrectomy. All rats were operated on during the 14 or 15 day of pregnancy. Maternal weight, serum urea and creatinine, number of fetal rats, fetal body and renal weight; DNA, RNA, protein and the amount of water in fetal kidneys were evaluated. RESULTS: Fetal kidneys showed a fall in weight in groups 3 and 4. In these groups tissue water concentration was lesser than groups 1 and 2. Fetal kidneys amounts of DNA, RNA and protein were similar in all groups. CONCLUSIONS: This study suggest that renotrophin could be a multifactorial system that can cross the placenta. The fall in renal fetal weight following maternal nephrectomy was consequent to a lesser tissue water content. Hypoplasia or hypotrophy did not play a role in this event. However, the fall in fetal kidney water was independent of the amount of maternal renal tissue that was removed. PMID- 7787865 TI - [Ophthalmological manifestations in AIDS: evaluation of 445 patients in one year]. AB - The authors prospectively evaluated 445 HIV positive patients for the presence of ophthalmological manifestations. PURPOSE--To evaluate patients HIV positive with or without AIDS and correlate the data with the ocular findings mentioned in the literature. METHODS--445 HIV positive patients (66% with AIDS) were evaluated in one year at the Paulista School of Medicine, Sao Paulo Hospital, Brazil. There was a predominance of males (87%) and homosexuals (58.2%). RESULTS--Of the 445 patients, 52% presented ocular findings secondary to HIV infection at the first examination. The diagnosis included: CMV retinitis (25%), ocular toxoplasmosis (8.5%), herpes retinitis (3.6%), papilledema (2.2%), optic atrophy (1.6%), phthisis bulbi (1.5%), multifocal choroiditis (1.2%), retinal hemorrhages (0.9%), syphilitic uveitis (0.6%) and central vein occlusion (0.2%). CONCLUSION--The incidence of ophthalmic manifestations of AIDS in Brazil is similar to that found in the international literature. We found though a higher incidence of ocular toxoplasmosis than that in other countries. No ocular pneumocystosis was presents in the population evaluated by us. PMID- 7787866 TI - [Pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation]. AB - Pharmacokinetics of cyclosporine shows high inter and intra-individual variability and changes in several parameters are often found after kidney transplantation. PURPOSE--Evaluate serial studies of the pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation. METHODS--The pharmacokinetics of cyclosporine and its metabolites were analyzed in 70 studies performed in 29 patients, 26 before and 44 after kidney transplantation. The blood cyclosporine concentration was determined in 17 samples obtained after is oral or intravenous administration, using radioimmunoassay with specific (RIE-MoSP) and nonspecific (RIE-MoNP) monoclonal antibodies. RESULTS--The values of area-under-the-time-concentration curve (AUC), bioavailability (F), peak concentration (Cmax) and the 12 and 24 trough levels (C12 and C24), determined with RIE-MoSP, were lower than that obtained with RIE MoNP, and the clearance (CL) and the volume of distribution (Vd) were higher. The elimination half-lives (t1/2) for both methods were not different. The absorption followed a zero order kinetic, demonstrating an inverse correlation between cyclosporine dose (mg/kg) and AUC/dose (r = -0.55, RIE-MoSP and r = -0.42, RIE MoNP). Bioavailability ranged between 18% and 68% (RIE-MoSP) and were overestimated when calculated using RIE-MoNP (38% to 100%) owing to extensive cyclosporine metabolization during the first passage through the intestine and the liver. The metabolic rate analyzed by the ratio of blood concentrations determined with RIE-MoNP and RIE-MoSP (NP/SP), increased during the first 12 hours after cyclosporine administration, and was higher after oral dosing. The hematocrit and the serum lipoproteins concentrations significantly correlated with several pharmacokinetics parameters, mainly when they were determined with RIE-MoSP. The correlation between one sample obtained at any time after cyclosporine administration and the AUC were unsatisfactory, even the trough levels of 12 and 24 hours. AUCs calculated with 3 selected samples chosen by multiple linear regression correlated with AUC calculated using 17 samples, with a determination coefficient higher than 0.95 (RIE-MoSP, r = 0.975; RIE-MoNP, r = 0.974). CONCLUSION--Among all the parameters calculated, parameters of total exposure to the drug (AUC, AUC/dose, Cssav) showed the best correlation with the dose of cyclosporine, hematocrit and serum lipoproteins concentration. The methodology simplification, reducing the number of samples to calculate AUC, could be a good strategy to apply routinely these parameters in clinical transplantation. PMID- 7787867 TI - [Serum beta 2 microglobulin (beta 2M) following renal transplantation]. AB - Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS- Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION -Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN. PMID- 7787868 TI - Anatomical terms of Yanomani Indians translated into Portuguese and English. AB - The authors translated into Portuguese and English the basic anatomical terminology used by the Yanomani indians. The knowledge of the names of organs and other parts of the human body and of a few having a clinical meaning should help those interested in the study of and in interaction with the Yanomanis. PMID- 7787869 TI - [Practicability of cataract surgery at university hospitals: searching for an economic model]. AB - Resources available for health care all over the world are not enough to cover all the demand in this sector. Cataract Free Zones conducted in many regions of the country show that only 10% to 20% of blind patients caused by senile cataract can get operated on. PURPOSE: To demonstrate feasibility of a model for cataract surgery with intraocular lens implantation at the Clinical Hospital from the University of Campinas, Unicamp, Sao Paulo, when considering the remuneration payed by the government for universitary services. METHODS: Costs with disposable material were collected for extracapsular cataract surgery, with posterior intraocular lens implant, at the Clinical Hospital, Unicamp. The model includes outpatient surgery under local anesthesia, and costs rationalization in acquisition and wear of material. University Hospitals have a different situation in the health system, where fixed costs and part of the variable costs of cataract surgery are subsidized by the State government. RESULTS: Cataract surgery performed under the proposed methodology is economically feasible, considering disposable components only, and the price achieved was US$ 77 with government payment of US$ 474. More surgical interventions increases the efficiency of the institution, provides more surgical training to residents and better community health care. CONCLUSION: The authors consider that it is an obligation of University Hospitals, regard their commitment with training, research and quality of eye care deliverance, to increase the number of cataract surgeries for the lowest possible price. PMID- 7787870 TI - [Microneurography: technique to study cardiovascular regulation by the sympathetic nervous system in humans]. AB - Microneurography is a valuable and safe method for direct intraneural recording of sympathetic nerve activity to muscle and skin in humans. The technique and its application for the study of autonomic function will be briefly discussed. The regulation of muscle sympathetic nerve activity will be focused in different clinical situations and or stimuli, such as: essential hypertension, mineralocorticoid induced hypertension, exercise mental arithmetic stress, cold pressor test, hyperinsulinemia, oral alcohol ingestion. PMID- 7787871 TI - [Leprosy and pregnancy]. AB - We followed 20 cases of pregnant women with leprosy: eight lepromatous (L), seven "borderline", four turbeculoid and only one indeterminate (I) and their newborns. Three patients showed the first symptoms during pregnancy and another one in postpartum. One patient was sick during sixteen years and another one was treated during fourteen years. The bacterioscopic examination was positive in thirteen and negative in seven patients. The Mitsuda test was negative in sixteen, positive in two and in two others was not performed. The treatment in fourteen patients was polychimiotherapy (diamino diphenylsulfone, rifampicin and clofazimine). Three patients received dapsone monotherapy. Three women started the treatment postpartum. Reactions states were treated with corticosteroids and acetylsalicylic acid. The therapy was Irregular in nine and Regular in eight cases. Ten patients showed reactions: eight during pregnancy, one in puerperium and one in the lactation period. Eight showed erythema nodosum leprosum and two reversal reaction. One patient showed false positive biologic test for syphilis and another one had positive bacterioscopic examination in the lactation period. One patient showed false positive biologic test for syphilis and another had positive bacterioscopic examination in the lactation period. One newborn showed exfoliative dermatitis in the first hours of life and his mother had used sulfone during pregnancy. Among the twenty babies five had less than 2,500g in weight and four were premature. CONCLUSION: The reaction states of patients and low birth weight of premature babies occurred in lepromatous and "borderline" cases. PMID- 7787873 TI - [Indications of exploration and repair of the orbital floor in fractures of the maxillozygomatic complex]. AB - Patients with orbital fractures may develop late complications like enophthalmos, orbital dystopia or diplopia, as a result of untreated orbital floor lesions, with herniation of orbital fat. Clinical and radiological findings are not enough for diagnostic and indication of orbital floor repair. PURPOSE: To evaluate the indication of repair of the orbital floor, during the surgical treatment of maxillozygomatic or zygomatic-maxillary compound fractures, by means of systemic exploration and to compare clinical with surgical findings. METHODS: 112 patients with unilateral zygomatic-maxillary compound fracture were submitted to exploration of the orbital floor, during the surgical treatment of the fracture. Open reduction and rigid internal fixation was performed with steel wire or miniplates. An autogenous conchal cartilage graft was used to repair the floor lesion, when there was bone loss of the inferior orbital wall and periorbita discontinuity, with fat herniation. RESULTS: The repair of the orbital floor was indicated in 46.4% of the patients. Early diplopia (before surgery) was observed in 26.6% and enophthalmos in 3.30% of the cases. Among patients with early diplopia, 60% needed repair, while 36.6% of the patients without early diplopia received cartilage graft. No important complications was observed. CONCLUSION: Orbital floor exploration is a complementary maneuver for the treatment of zygomatic-maxillary compound fractures that permits the precise diagnostic of the lesion and the correct indication of repair. PMID- 7787874 TI - [Deprofessionalization or reprofessionalization: a study comparing law and medicine]. AB - The author discusses and compares the transformations in the profession of lawyers in the United States of America and the doctors in Brazil according to a theoretical analysis based upon the classical theory of the Sociology of the Professions. The discussion about the deprofessionalization of Medicine is conducted along some of the characteristics outlined by the theory. The author concludes that the challenge that faces medicine is a kind of re-organization that will change necessarily the profession as we know it today, but this change will not affect the professional autonomy or any other of its essential characteristics. PMID- 7787872 TI - [Transduodenal endoscopic drainage of pancreatic pseudocysts and peripancreatic collection]. AB - Until recently, the treatment of pancreatic pseudocysts was mainly surgical. However, two non-surgical invasive approaches are now possible: percutaneous aspiration under ultrasonic or CT monitoring and endoscopic drainage. PURPOSE--To report the result obtained using endoscopic drainage of pancreatic pseudocysts. METHODS--11 consecutive patients admitted with pancreatic pseudocyst had chronic pancreatitis and 1 patient had a well defined paraduodenal collection originated from acute necrotising pancreatitis. Endoscopic cystoduodenostomy was performed in the area of close contact with the digestive wall. A standard Olympus duodenoscope was used to reach the bulging wall and to allow the diatermic fistula. RESULTS--The success rate was 91.7%. Hemorrhage occurred in 1 patient (8.3%) controlled without blood transfusion. Endoscopic cystoduodenostomy was the definitive treatment in 10 patients 36 months after the procedure. One patient underwent gastrojejunostomy after 14 months for duodenal obstruction following relapsing pancreatitis. There was no relapsing cyst. There was no death following the endoscopic procedure. CONCLUSION--the endoscopic cystoduodenostomy constitutes an alternative procedure for the drainage of paraduodenal pseudocysts whenever restricted to the precise morphological indication of paraintestinal pseudocyst bulging into the duodenal lumen. PMID- 7787876 TI - [Leptospirosis and pulmonary hantavirus syndrome]. PMID- 7787875 TI - [Molecular aspects of erythrocyte membrane disorders]. PMID- 7787877 TI - [Osteocalcin]. PMID- 7787878 TI - Apoptosis and the cell cycle. AB - This brief review examines the strict relationships between cell apoptosis and G1 cyclins. It has been shown that the basic role of G1 cyclins is in regulating G1 progression and G1/S transition (the critical cycle point for cell program decisions, including apoptosis) a fatal program for cells unable to bypass G1/S checkpoint 1. Notably, both of the two giant regulators of checkpoint 1 (i.e., p105RB [retinoblastoma oncosuppressor-encoded protein] and p53 dependent WAF1/CIP1) are influenced by or influence G1 cyclins: cyclin E/cdk2 kinase complexes hyperphosphorylate p105RB, induce E2F release, and free G1 exit. On the other hand, p21-WAF1/CIP1 is an inhibitor of cyclin-dependent kinases blocking cells at G1/S. Thus, G1 cyclin activity appears as a conditio sine qua non for G1 exit and apoptosis escape. PMID- 7787879 TI - The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis. AB - Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, the brown locus encodes TRP1 (tyrosinase-related protein-1), and the slaty locus encodes TRP2, another tyrosinase related-protein. TRP2 functions as DOPAchrome tautomerase, an enzyme that preserves the carboxylic acid content of melanins, which would be spontaneously lost in its absence, while TRP1 is able to oxidize the DHICA produced by TRP2. In this study we have used three different systems (immune affinity purified melanogenic enzymes, mutant melanocytes, and transfected cells) to examine the enzymatic interactions of these proteins, and their stabilization in a complex which significantly increases their physiological half-life. When extrapolated to the melanocyte, our results demonstrate the catalytic functions of these proteins and suggest how they might stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized. PMID- 7787880 TI - Identification of a rat protein tyrosine phosphatase gene preferentially expressed in the embryonal brain. AB - We have identified a novel protein tyrosine phosphatase gene from an embryonal rat brain by reverse transcription-based polymerase chain reaction. Its transcription is specific to brain and is developmentally regulated, as it is expressed at high levels in embryonal and neonatal stages but scarcely in an adult. Southern blot analysis indicates that the gene exists as a single copy and is conserved among various species. Homology search of the deduced amino acid sequence suggests that this gene belongs to the same family of the membrane-type tyrosine phosphatase gene of Drosophila (DPTP10D), whose expression is specific to an central nervous system of fly embryo. PMID- 7787881 TI - Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E. AB - Synthesis of the mammalian growth-related protein P23 is rapidly induced after serum stimulation of mouse fibroblasts and Ehrlich ascites tumour cells. This induction occurs at the translational level. Growth-induction leads also to an increase in phosphorylation of the rate-limiting initiation factor eIF-4E. Here, we present the following evidence indicating the involvement of eIF-4E in the regulation of P23 synthesis: 1) P23 synthesis is induced by the same mitogenic stimuli which lead to enhanced eIF-4E phosphorylation. 2) Upon heat shock treatment of Ehrlich ascites cells (which results in immediate dephosphorylation and concomitant inactivation of eIF-4E), P23 synthesis is rapidly shut off. 3) In control NIH 3T3 cells, P23 synthesis is readily induced by growth stimulation. This response is strongly diminished in cells overexpressing eIF-4E, and the basal level of P23 synthesis is elevated in these cells. Overexpression of a nonfunctional mutant of eIF-4E diminishes the basal level of P23 synthesis as well as the serum-response of the cells with respect to P23 induction. 4) Cells transformed by overexpression of the ras or src genes in which eIF-4E is highly phosphorylated do not show any inducibility of P23 synthesis. 5) HeLa cells expressing antisense RNA of eIF-4E, have reduced levels of eIF-4E/F and show reduced rates of growth and protein synthesis. In these cells the total amount of P23 protein is about 50% compared with control cells. The results suggest that P23 is one of the gene products, the synthesis of which is regulated by eIF-4E activity. PMID- 7787882 TI - In vivo binding of proteins to stably integrated MMTV DNA in murine cell lines: occupancy of NFI and OTF1 binding sites in the absence and presence of glucocorticoids. AB - Activation of expression at the mouse mammary tumor virus (MMTV) promoter is thought to be controlled by nucleosome positioning. On stably integrated MMTV DNA, the long terminal repeat (LTR) region is organized in a phased array of nucleosomes which allegedly occludes transcription factors such as NFI from binding. NFI only binds to the promoter region when the ordered nucleosome structure is apparently disrupted by activated steroid hormone receptors in hormone induced transcription. In certain cell lines, binding sites for the transcription factors NFI and OTF1 are however required for hormone-independent expression of MMTV. We have used stably transfected mouse NIH3T3 and GR cells that exhibit detectable MMTV expression in the absence of hormone for in vivo determination of proteins binding to the MMTV promoter. Here, we present in vivo dimethyl sulfate footprinting data that show that the NFI and OTF binding sites are permanently occupied in vivo in these cells. The contacting guanine residues identified in vivo were demonstrated in in vitro methylation interference assays to correspond to binding by NFI and OTF1. These results demonstrate a novel feature of transcription factor occupancy at the MMTV LTR promoter. PMID- 7787883 TI - TGF-beta 1 augments expression of the TIS10/prostaglandin synthase-2 gene in intestinal epithelial cells. AB - Treatment of nontransformed rat intestinal crypt epithelial IEC-6 cells with tetradecanoyl phorbol acetate (TPA) + calcium ionophore (A23187) induces both the synthesis of prostacyclin and the expression of the TIS10/PGS-2 gene, a primary response gene encoding a second form of prostaglandin synthase (PGS). In addition to pharmacological induction by TPA + A23187, TIS10/PGS-2 message is also induced by the inflammatory cytokine interleukin 1-beta (IL-1 beta). Transforming growth factor beta 1 (TGF-beta), a potent cytokine known to modulate a variety of biological responses, does not by itself induce either prostanoid accumulation or TIS10/PGS-2 gene expression. TGF-beta does, however, augment both induced prostacyclin accumulation and the induced synthesis and accumulation of TIS10/PGS 2 protein and message in IEC-6 cells. TGF-beta concentrations in the range of 0.1 1.0 ng/ml (4.0-40 pM) maximally augment accumulation of TIS10/PGS-2 message. In contrast, dexamethasone attenuates prostacyclin production, TIS10/PGS-2 protein accumulation, and TIS10/PGS-2 message induction in IEC-6 cells. These results suggest that steroids and cytokines such as TGF-beta may (i) modulate intestinal epithelial cell growth and differentiation and (ii) influence gastrointestinal diseases such as gastric ulcers and colon cancer by modulating eicosanoid production. PMID- 7787884 TI - Emergence of antigenic variants of simian immunodeficiency virus (SIVmac) in a seronegative macaque after SIVmac239 infection. AB - Infection with the macaque strain of the simian immunodeficiency virus (SIVmac) induces simian immunodeficiency syndrome in rhesus macaques. This report describes the isolation and identification of antigenic variants of SIVmac in one of the infected monkeys (macaque #22803). Eight naive rhesus monkeys were inoculated with a titered viral stock of the molecularly cloned SIVmac239. Standard serological analysis revealed that all but two were seroconverted. Western blot analysis confirmed the seronegativity of macaque #22803. In addition, sera recovered from this monkey were not able to neutralize the parent SIVmac239. However, virus could be isolated from all of the infected animals, including macaque #22803. Sera recovered were reactive to the autologous virus. The results suggest that the virus from macaque #22803 may have undergone extensive antigenic shift in vivo. To test this hypothesis, a portion of the gag gene was amplified by the polymerase chain reaction (PCR), cloned, and sequenced. Sequence analysis revealed amino acid changes that were clustered between amino acids 200-245. Evaluation of the possible selective pressures contributing to the observed viral mutation revealed that in comparison with the other SIVmac239 infected monkeys, macaque #22803 produced an unusually high T cell proliferative response toward mitogen stimulation before infection, and continued to display a persistently high plasma viremia titer after infection. PMID- 7787885 TI - Characterization of the interactions between double-stranded RNA and the double stranded RNA binding domain of the interferon induced protein kinase. AB - The interferon-inducible protein kinase, PKR, requires double-stranded (ds) RNA for its activation. We have previously mapped its dsRNA-binding domain (DRBD) to the amino terminal 170 residues (Patel and Sen, 1992). In the present study, we have characterized in detail the interactions between dsRNA and DRBD. For this purpose, DRBD was produced in bacteria as a polyhistidine-tagged protein and purified by affinity chromatography. A polyclonal antibody was raised against purified DRBD. For studying dsRNA-DRBD interactions, a Northwestern assay and an electrophoretic mobility shift assay (EMSA) using a radiolabeled in vitro transcribed 82 bp dsRNA probe was developed. The antiserum reacted with both DRBD and PKR but did not prevent their interactions with dsRNA. DRBD, on the other hand, blocked the activation of PKR by dsRNA. DRBD and the dsRNA probe formed multimeric complexes which were separable by EMSA. The antibody could interact with these complexes and supershift their mobility. Competition with unlabeled dsRNA revealed that the dimeric DRBD-dsRNA complex was much more stable than the monomeric complex. Similar competition assays using 11 different synthetic and natural RNA molecules revealed that only authentic dsRNA molecules could effectively compete with the probe for binding DRBD in a sequence-independent fashion. PMID- 7787886 TI - Dinucleotide repeat polymorphisms at nine loci in sporadic colorectal cancer. AB - Genomic instability in the form of microsatellite alterations at nine loci on chromosomes 2p, 8p, 10p, 11p, and nm23-H1 locus on 17q21.3 were studied in sporadic colorectal tumors. Alterations in dinucleotide repeats in tumor DNA as larger allele, smaller allele, or loss of heterozygosity (LOH) were observed. Forty percent of tumor showed an RER+ phenotype. A significantly high number of alterations was detected at loci of chromosome 8p. The markers on chromosomes 2p, 10p, and 11p did not show such significant alteration. LOH was found to be associated with the nm23-H1 locus. No correlation was found between the age, site of tumor occurrence, or metastasis and the microsatellite instability. PMID- 7787889 TI - Bibliography of cellular and molecular biology research. PMID- 7787887 TI - Cloning of the chandipura virus phosphoprotein encoding gene and its expression in Escherichia coli. AB - Chandipura (CHP) virus, a member of the vesiculovirus genus within the Rhabdoviridae family, was first isolated from human patients in India. The full length phosphoprotein P gene of CHP have been cloned and expressed in Escherichia coli using the T7 polymerase-based pET-3 series of expression vectors. Under optimal conditions of induction with IPTG, the recombinant P protein constituted 35% of the total bacterial protein. The bacterially expressed protein was found to be phosphate-free. Deletion analysis suggested that the anomalous mobility of the P protein was due to its high acidity. The expressed protein can be phosphorylated in vitro by the extracts prepared from baby hamster kidney cells or rabbit reticulocytes. The cellular kinase involved in phosphorylation appears to be casein kinase II. PMID- 7787890 TI - Birthing the placenta. Tear prevention. PMID- 7787888 TI - Position and orientation independent transactivation by c-Myc. AB - The c-myc oncogene c-Myc is commonly activated in cancer and transactivates gene expression by binding to CACGTG DNA sequences as a heterodimeric complex with Max. The ornithine decarboxylase (ODC), p53, prothymosin alpha and ECA39 promoters are transactivated by c-Myc, and are considered direct targets, as activation is mediated by CACGTG sequences. Interestingly, the c-Myc-responsive CACGTG sequences in the p53, prothymosin alpha, ECA39 and murine ODC genes are all downstream of the RNA CAP site, suggesting that downstream sequences are preferred c-Myc targets. Using a series of heterologous reporter constructs, we have tested the effects of position and orientation of c-Myc-responsive CACGTG sequences on c-Myc's ability to activate transcription. A single binding site conferred c-Myc-responsiveness independent of position and orientation, and over distances of 1.7 kbp. The extent of transactivation was not significantly influenced by position of the responsive elements. By contrast, the extent of transactivation was dependent upon the number of c-Myc binding sites. The results demonstrate that c-Myc activates transcription independent of position and orientation and that considerable flexibility exists in the interaction of c-Myc transactivation domains with the general transcription machinery. PMID- 7787891 TI - Wisdom from generations past. PMID- 7787893 TI - Sage femme. PMID- 7787892 TI - Crucial timing. PMID- 7787894 TI - The grand finale to birth. PMID- 7787895 TI - The last minutes before parenthood. PMID- 7787896 TI - Alexander. PMID- 7787897 TI - Unraveling toxemia. PMID- 7787898 TI - One diaper at a time. PMID- 7787899 TI - Signs to watch. PMID- 7787900 TI - The physiology of fetal transformation at birth. PMID- 7787901 TI - Dance with life. PMID- 7787902 TI - Little black book pages for third stage and postpartum. PMID- 7787903 TI - Traditional Chinese medicine: integrating it into modern midwifery practice. PMID- 7787904 TI - Meconium aspiration syndrome: diagnosis and care guidelines. PMID- 7787906 TI - Expelling clots. PMID- 7787905 TI - Postpartum hemorrhage: prevention and treatment. PMID- 7787907 TI - TCM terminology. PMID- 7787908 TI - Tips for bimanual compression. PMID- 7787909 TI - A chance to define our future. PMID- 7787910 TI - Lessons from history and from down under. PMID- 7787911 TI - Acute care nurse practitioner curriculum: content and development process. AB - Curriculum development for preparation of acute care nurse practitioners requires a comprehensive process. To develop a program for their preparation at a large university, the faculty examined needs of the target patient population and care delivery system; scope of acute care nurse practitioner practice; current guidelines for the education of primary care nurse practitioners; evolving guidelines for the didactic and clinical education of acute care nurse practitioners; educational requirements of governing or licensing and certifying bodies; and placement of this new role within the existing healthcare team structure. A curriculum was then developed using a collaborative, multidisciplinary approach. PMID- 7787912 TI - Effect of a standardized rewarming protocol and acetaminophen on core temperature after coronary artery bypass. AB - BACKGROUND: Cardiac surgical patients who require hypothermic cardiopulmonary bypass experience hypothermia, normothermia, and hyperthermia during the early postoperative period. Research-based rewarming protocols are needed to manage temperature variations. OBJECTIVE: To describe the effect of a standardized rewarming protocol and acetaminophen on the following outcome variables: core temperature, peak core temperature, rewarming time, and hyperthermia. METHODS: Patients (N = 60) were rewarmed using a standardized rewarming protocol. Electric heating blankets were used for subjects with core temperatures less than 36 degrees C on admission to the intensive care unit; other subjects were covered with cotton bath blankets. Subjects were also assigned to one of three acetaminophen groups (650 mg at 38.1 degrees C, 650 mg at 37 degrees C, 1300 mg at 37 degrees C). RESULTS: Using the protocol, subjects warmed to normothermia in 3.6 to 6 hours. The 16-hour core temperature thermal curves of heating blanket versus cotton bath blanket subjects differed significantly; thermal curves of the acetaminophen groups were similar. Peak core temperature was significantly lower in heating blanket subjects and unaffected by acetaminophen group. The onset of hyperthermia was not significantly affected by the method of rewarming (electric heating blanket versus cotton blankets) or acetaminophen group. Rewarming time was significantly longer for electric heating blanket subjects. CONCLUSIONS: Our results indicate that mildly hypothermic subjects rewarmed with electric heating blankets during the early postoperative period have lower peak core temperatures and longer rewarming times than those rewarmed with cotton bath blankets. Acetaminophen administration at normothermia does not significantly affect peak core temperature or the onset of hyperthermia. PMID- 7787913 TI - Comparison of nasogastric tube securing methods and tube types in medical intensive care patients. AB - BACKGROUND: Nasogastric tube displacement can result in serious complications such as aspiration and inadvertent migration of the tube into the lungs. Replacement of the tubes is costly, time- and effort-intensive, uncomfortable for the patients, and potentially dangerous. OBJECTIVE: To determine the best of three methods for securing nasogastric tubes in a medical intensive care population and to identify variables related to the failure of tube securing methods. METHODS: A convenience sample of 103 patients requiring duodenal or standard gastric tubes for feeding, medication delivery, or decompression were randomly assigned to one of three taping methods: pink tape, clear tape, or "butterfly," for a total of 264 taping episodes. Data collection included the mean time until failure of the securing methods as well as variables such as patient alertness and mobility. RESULTS: The mean time until failure was 100 hours with pink tape versus 56 hours with clear tape and 30 hours with the "butterfly." Differences were significant. Duodenal tubes stayed secured longer than standard sump tubes (mean time until failure was 86 vs 41 hours) for all taping methods, but not significant relationship was demonstrated between mean time until failure and variables such as alertness, sedation, confusion, mobility, and the use of restraints. CONCLUSION: Our results showed that the pink tape method was superior. Nasogastric tube securing methods in adult critical care patients vary in efficacy and should be selected carefully. PMID- 7787914 TI - Infectious complications associated with ventricular assist devices. AB - Improvements in technology, patient selection, and patient management have led to a wider clinical application of mechanical circulatory support. Critically ill patients often develop multiorgan ischemia and are prone to multiple complications. Despite these advances, infection is a common and sometimes lethal complication of support with ventricular assist devices. This article provides guidelines for the prevention and management of infection in patients who require such support. PMID- 7787915 TI - Postoperative circadian rhythms and cortisol stress response to two types of cardiac surgery. AB - BACKGROUND: Although endocrine stress responses of coronary artery bypass patients have been reported, similar studies have not been conducted in patients undergoing implantation of an automatic cardioverter/defibrillator device. OBJECTIVES: To compare patterns and magnitudes of intra- and postoperative cortisol stress responses in patients undergoing two types of surgery; rate at which postoperative cortisol levels return to presurgical levels; and whether stressors associated with these two procedures affect postoperative circadian rhythms of cortisol, heart rate, and body temperature. METHODS: A time-series, small-group design was used to investigate 16 coronary artery bypass graft and 9 automatic cardioverter defibrillator patients. For the cortisol stress study, blood samples were obtained pre-, intra-, and postoperatively until day 6. For the circadian rhythm aspect, cortisol circadian rhythm aspect, cortisol levels, heart rate, and oral temperatures were measured every 2 hours for 24 hours beginning on postoperative day 1. RESULTS: Plasma cortisol levels increased significantly toward the latter part of surgery. Generally, no significant group differences were found in cortisol magnitude during and after surgery. Postoperative cortisol levels were significantly elevated from preoperative levels for both groups; however, the automatic cardioverter defibrillator group's cortisol levels declined at a slower rate. The stressors associated with these surgeries were sufficient to disrupt or abolish circadian rhythms for the measured variables. CONCLUSIONS: The elevated postoperative cortisol levels and altered circadian rhythms may contribute to increased vulnerability by dampening patients' anti-inflammatory and immunologic responses and adversely affecting their sense of well-being. The clinical significance of these findings is yet to be determined; more research is warranted. PMID- 7787916 TI - A randomized clinical trial of the effect of bed position after PTCA. AB - BACKGROUND: After percutaneous transluminal coronary angioplasty, prolonged supine bedrest with the bed flat frequently causes back pain. This study was conducted to examine whether percutaneous transluminal coronary angioplasty patients could adjust their bed position to make themselves comfortable without increasing the frequency or severity of bleeding complications. OBJECTIVES: To determine whether the risk of bleeding increased in patients who were allowed to use their bed controls to make themselves comfortable, and if the difference in comfort was significant between patients who controlled and elevated their bed position and patients who remained flat in bed. METHOD: A randomized clinical trial was conducted; 54 patients undergoing percutaneous transluminal coronary angioplasty were randomly assigned to either the control group, in which patients remained flat in bed, or the experimental group, in which they controlled their bed position. Outcome measures included amount of bleeding at the catheter sites and patient comfort. RESULTS: No difference in the amount of bleeding at catheter insertion sites was found between the two groups. Few subjects reported pain at any time. Back pain at dinner and bedtime was higher in the control group, but only the bedtime difference was statistically significant. CONCLUSION: We conclude that patients may be allowed to adjust their bed position to 30 degrees for comfort without incurring increased risk of catheter entry site bleeding and that requiring patients to remain flat in bed has no scientific basis. PMID- 7787917 TI - The unconscious experience. AB - BACKGROUND: Although considerable research has been done on pathophysiology, metabolic and physical causes, and prognostic indicators, little is known about unconsciousness or coma from the perspective of the patient. OBJECTIVE: To describe the experiences of patients who were once documented as being unconscious. METHODS: Phenomenologic interviews were conducted with 100 patients whose records indicated that they had been unconscious during hospitalization. Interviews were also attempted with primary family members, significant others, or other external observers. Chart audits documenting the unconscious episode, medications, and diagnoses were also carried out. Data were compared, using van Kaam's method, and contrasted. RESULTS: Patients experienced one or more of five states: unconsciousness, inner consciousness, perceived unconsciousness, distorted consciousness, and paranormal experiences. They described hearing, understanding, and responding emotionally to what was being said when it was assumed they were not aware. In addition, 23 subjects reported near-death experiences or visits, out-of-body experiences, or some other paranormal experience. CONCLUSION: Patients' unconscious experiences can cause long-term effects. Patients often need reassurance that other patients subjected to similar conditions also have these experiences. PMID- 7787918 TI - Psychophysiologic responses of mechanically ventilated patients to music: a pilot study. AB - BACKGROUND: Although mechanically ventilated patients experience numerous stressors, they have not been included in music therapy stress reduction and relaxation studies. OBJECTIVE: To examine selected psychophysiologic responses of mechanically ventilated patients to music. METHODS: A two-group experimental design with pretest, posttest, and repeated measures was used. Twenty mechanically ventilated patients were randomized to a music-listening group or a nonmusic (headphones only) group. Physiologic dependent measures--heart rate and rhythm, respiratory rate, systolic and diastolic blood pressure, oxygen saturation, and airway pressure--were collected at timed intervals. Psychologic data were collected before and after intervention using the Profile of Mood States. RESULTS: Using repeated measures analysis of variance, results for heart rate and respiratory rate over time and over time between groups were significant. Between-group differences were significant for respiratory rate. Significant differences were found via t test for the music group's Profile of Mood States scores. No adverse cardiovascular responses were noted for either group. CONCLUSIONS: Data indicated that music listening decreased heart rate, respiratory rate, and Profile of Mood States scores, indicating relaxation and mood improvement. PMID- 7787919 TI - Sudden death in athletes. AB - HCM, as well as coronary and myocardial structural abnormalities, is the most common pathology leading to SCD in young athletes. Furthermore, SCD from fatal arrhythmia seems to be the most common mechanism of death. In this population, however, data are insufficient to support either invasive or noninvasive approaches to clarify risk stratification for SCD. Because of the large population, variants of normal found within the athletic population, and the rarity of the disease, screening for individuals at risk is neither practical nor cost-effective. Not all athletes with HCM are at the same risk for SCD; a thorough history and physical examination should alert the health professional to potential risk factors. Efforts are under way to stratify athletes at risk for SCD to determine who can participate in competitive sports and who should not. However, until research can accurately define variables of hemodynamic and electrical instability that permit reliable identification of athletes with HCM who are at risk for SCD, the recommendation is to disqualify athletes with confirmed HCM from moderate- to high-intensity competitive sports. This recommendation includes athletes with or without symptoms or left ventricular outflow obstruction. Due to the decreased risk of SCD in older athletes, individual judgment of eligibility may be used. Athletes thought to have had myocarditis should be withdrawn from all competitive sports for a convalescent period of approximately 6 months, with thorough cardiac assessment and testing performed before returning to training. Athletes with atrial or ventricular tachyarrhythmia must be screened for structural abnormality, heart response during exercise, and the frequency and duration of the arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787920 TI - Outcome of an exercise to notify patients treated by an obstetrician/gynaecologist infected with HIV-1. AB - Experience with hepatitis B suggests that the risk of HIV transmission from a health care worker infected with HIV to a patient will be greatest during major surgical procedures. The number of patients worldwide who are known to have undergone such procedures, been notified, and subsequently tested is still too small to be confident that the risk of HIV transmission in these circumstances is negligible. We describe a patient notification exercise, undertaken in the United Kingdom in 1991. Attempts were made to contact 1217 patients, in three health districts (A, B, and C), who had undergone surgical procedures performed by an obstetrician/gynaecologist who was infected with HIV. The exercise aimed to offer the patients reassurance, counselling and--if they wished--HIV testing. One thousand one hundred and forty-two patients (94%) were contacted, and all 520 who elected to be tested were negative for anti-HIV. The proportion of identified patients tested was 63% in district A, 35% in district B, and 61% in district C. Surgical procedures were classified retrospectively according to the likely risk (none, possible, or high) of exposure to the doctor's blood and, therefore, risk of HIV transmission. One hundred and ninety-five of those tested had undergone a procedure that carried a high risk of exposure; 179 had undergone a procedure thought to carry no risk. Patients in districts A and C who had undergone a procedure that carried a high risk of exposure were more likely to be tested than those who had not; 206 patients overall had undergone procedures that carried a high risk of exposure but were not subsequently tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787921 TI - COVER (COVER of vaccination evaluated rapidly): 31. PMID- 7787922 TI - A case control study of infection with an epidemic strain of multiresistant Salmonella typhimurium DT104 in England and Wales. AB - Laboratory reports of a multiresistant strain of Salmonella typhimurium definitive type (DT) 104 rose in 1993; this led the Public Health Laboratory Service to investigate cases and identify possible risk factors for infection. Information derived from questionnaires, and details of previous isolations of S. typhimurium DT104 from food and animals, were used to design an unmatched case control study. Eighty-three cases whose isolations were of the same plasmid profile type (the 'epidemic strain') and 235 controls were included in the analysis. Illness was independently associated with the consumption of several food items and contact with animals, particularly ill farm animals. The number of isolations of this organism continues to rise, and control measures may include reducing infection in animals used for food, reducing the risk of contamination at all stages of the food chain, and raising awareness of measures to prevent food poisoning among food handlers and the general public. PMID- 7787923 TI - Associations between human and farm animal infections with Salmonella typhimurium DT104 in Herefordshire. AB - Reports of human infection with Salmonella typhimurium definitive type (DT) 104 have generated considerable interest. We undertook a descriptive study of infections with S. typhimurium DT 104 infection in humans and farm animals in Herefordshire between 1991 and 1993. Laboratory reports of human salmonellosis, sent to the consultant in communicable disease control, were compared with cases identified using Statutory Incident Reports of salmonella in animals, birds and their products, received from the Ministry of Agriculture, Fisheries and Food. Six separate associations of infection between farming families and their livestock were identified. Nine out of 23 human cases, including three family outbreaks, were associated with animal infection. This study suggests that occupationally acquired infection in farmers and their families may be contributing to the national increase in cases, and shows the value of drawing together data from human and animal sources for the surveillance, investigation, and control of human infection with S. typhimurium DT104. PMID- 7787924 TI - Viral haemorrhagic fever: outbreak in Zaire. PMID- 7787925 TI - Fetal toxicology of environmental tobacco smoke. AB - During the past decade, new evidence has been collected regarding the fetal risks of environmental tobacco smoke. Throughout gestation, the unborn baby is exposed to increasing concentrations of nicotine through maternal blood and gastrointestinal and skin absorption of the nicotine in the amniotic fluid. Recent research shows measurable concentrations of cotinine in the hair of infants born to passively smoking mothers. This exposure has been recently associated with effects on fetal growth. PMID- 7787926 TI - Cerebral perfusion, metabolism, and outcome. AB - Factors contributing to brain damage and an adverse outcome are complex. Both severe hypoxia-ischemia and prolonged hypoxia of lesser severity may cause brain damage. Compromised cerebral perfusion leads to ischemia. Fetal brain damage may begin because of a redistribution rather than reduction of cerebral blood flow. Normal newborn cerebral blood flow is low; fetal asphyxia at birth causes delayed cerebral hyperperfusion in the neonate. The threshold of newborn cerebral blood flow that is associated with brain damage has not yet been established. Hypoxia ischemia will disrupt cerebral metabolism. The fetus can compensate for hypoxia up to a point; however, decompensation will occur when acidosis becomes severe. Normal newborn cerebral oxygen consumption is low compared with that in the adult; however, asphyxia, causing brain damage, is associated with abnormal newborn cerebral metabolism. Supplementary glucose may have a protective effect in the newborn brain. Hypoxia-ischemia will cause brain damage in the human fetus and neonate. There is a threshold of fetal asphyxia at birth when brain damage may occur. Sustained neonatal hypotension and hypoxemia are associated with brain damage and an adverse outcome. PMID- 7787927 TI - Potential for treatment of anemia of prematurity with recombinant human erythropoietin. AB - Anemia of prematurity (AOP) results from several interacting processes, including phlebotomy losses, a temporary failure to release erythropoietin in response to anemia, a short life span of erythrocytes, and rapid growth of body mass and, hence, blood volume after the first few weeks of life. Infants with AOP have erythroid progenitors that respond to erythropoietin in vitro, suggesting that treatment with recombinant erythropoietin might reduce the need for transfusions for AOP. Many pilot studies were needed to define the dose of recombinant erythropoietin (500 to 750 U/kg/wk) that stimulated the early onset of erythropoiesis in infants with AOP. Three large controlled trials have demonstrated that recombinant erythropoietin therapy reduces transfusions in AOP and is apparently safe. Unresolved issues include the ideal dose, the optimal nutrition needed during therapy, the target population, and timing of the start of treatment. PMID- 7787929 TI - A neonate with meconium aspiration syndrome and severe respiratory distress. PMID- 7787928 TI - Nutrition in the neonate. AB - Good nutrition is of great importance for all living individuals, especially for the rapidly growing newborn infant. Nutrition is needed not only for the maintenance of physiologic functions but also for growth. Despite extensive research in this field, numerous questions remain regarding the nutrition of the term as well as the preterm infant. It should be stressed that the requirements of term infants are different from those of preterm infants, and a further distinction has to be made between very low birth weight and extremely low birth weight infants. In this review, the following issues are addressed: breastfeeding versus formula feeding, the role of polyunsaturated fatty acids, nutrition of the infant with bronchopulmonary dysplasia, and parenteral nutrition. PMID- 7787930 TI - Management of children with serious renal disorders in the era of managed care. Commentary. PMID- 7787931 TI - Hemolytic uremic syndrome in children. AB - The majority of postdiarrheal hemolytic uremic syndrome is caused by Escherichia coli O157:H7. The organisms are carried in the intestines of cattle; partially cooked contaminated hamburger is the single most common vector. The E. coli produce a potent cytotoxin that gains access to the circulation, is taken up by glycolipid receptors on glomerular endothelial cells, is internalized, and causes cell death. Associated phenomena include the activation of platelets, leukocytes, and the coagulation cascade, as well as the production of cytokines. Although some patients experience a mild or incomplete syndrome, life-threatening multisystem involvement can occur. Treatment is supportive, but plasma exchange may be useful in selected high-risk subsets. Efforts to prevent colitis from evolving into hemolytic uremic syndrome include the oral administration of material to bind the toxin in the gut. Mortality remains at 5% to 10%; about 4% are left with end-stage renal failure, and approximately 50% suffer mild chronic kidney damage. PMID- 7787932 TI - Reflux nephropathy, urinary tract infection, and voiding disorders. AB - Urinary tract infection (UTI), vesicoureteral reflux (VUR), and certain voiding disorders result in renal damage. In the past few years, the increasing use of 99mTc-dimercaptosuccinic acid renal scans, urodynamic testing, and antenatal sonography have helped shed light on the interrelationship of these disorders. Renal parenchymal involvement during acute febrile UTI and subsequent renal scarring are quite commonly observed in the absence of VUR, suggesting that the presence of reflux is not a prerequisite for renal damage. In infants with gross VUR, renal damage is often present at birth even before the development of any UTI. High intravesical pressures during bladder filling and voiding are commonly observed in infants with gross VUR, reflecting an underlying voiding dysfunction. High voiding detrusor pressures are also commonly observed in infants presenting with symptomatic UTI who do not have VUR. Children with dysfunctional voiding states are at risk for development of VUR and UTI. Renal damage in these children may occur in the absence of one or the other. This review elucidates how voiding dysfunction predisposes children to bacterial colonization of the bladder, the development or perpetuation of VUR, and renal damage. PMID- 7787933 TI - Chronic renal disease and growth in childhood. AB - Growth failure, sometimes of a severe nature, has been recognized for many years as a consequence of chronic renal insufficiency (CRI) in childhood. The factors associated with growth failure, including renal osteodystrophy, anorexia and malnutrition, acidosis, salt wasting, and anemia, have also been recognized for many years. Despite vigorous treatment of these factors, patients with CRI continue to grow poorly. It was hoped that, with modern dialysis and transplantation, these patients would have normal growth or even catch-up growth and therefore overcome the height deficit that accrued during the time they had CRI. Unfortunately, this has not been the case. Although normal growth may be seen after transplantation, catch-up growth is rare. In the past year, studies have been reported demonstrating that supraphysiologic doses of growth hormone will produce catch-up growth in children with CRI. These reports are encouraging and are reviewed here. PMID- 7787934 TI - Focal segmental glomerulosclerosis in children. AB - Idiopathic focal segmental glomerulosclerosis is a histologic diagnosis that usually presents as the nephrotic syndrome but, unlike minimal change disease, often leads to renal failure in children. Standard therapies used to treat the proteinuria are often futile, and thus patients are at risk for the multiple complications resulting from persistent, severe proteinuria. Eventually, end stage renal failure ensues, and the possibility of the disease recurring in the transplanted renal allograft is worrisome. This report reviews the clinical features and outcomes of idiopathic focal segmental glomerulosclerosis in children, the response to newer treatment options, and new insights into understanding what factors may be involved in causing the disorder. PMID- 7787936 TI - Status of drug approval processes and regulation of medications for children. AB - The term therapeutic orphan was coined in 1968 to describe the exclusion of infants and children from approved indications for use of the majority of drugs approved by the US Food and Drug Administration (FDA). Although the 1962 Kefauver Harris amendments to the Food, Drug, and Cosmetic Act were designed to insure the efficacy and safety of drugs approved for human use, infants and children have largely been excluded from the protection of the law. Approximately 80% of the drugs approved by the FDA during the past 30 years have been approved with a labeling disclaimer for use by children. This high percentage is due largely to the lack of studies in children to document safety and efficacy or a failure to use available data to amend labeling to include pediatric indications. Recently, several initiatives by the FDA and the National Institute of Child Health and Human Development have been implemented that promise to increase the number of drugs studied and labeled for children. These initiatives may introduce a new era of drug development for children in which pediatric investigators, the FDA, the National Institutes of Health, and the pharmaceutical industry join together to bring the same level of pharmacotherapeutic safety and efficacy to children that adult patients enjoy. PMID- 7787935 TI - Genetic renal diseases in children. AB - In this review, a survey is given of genetic renal diseases in which recent progress has been made regarding the study of their molecular genetics. Diseases in which the responsible gene has been identified are discussed first, followed by a description of diseases in which successful chromosomal mapping has been achieved. The recent progress in this field will lead to advances in the diagnosis and understanding of the pathogenic mechanisms of genetic renal diseases and, potentially, will have implications for therapeutic interventions. The International Studies of Genetic Renal Diseases, which promotes the study of genetic renal disease, has recently provided an international database called kidbase, which is accessible via the Internet. PMID- 7787937 TI - Pharmacotherapy of depression in children. AB - Depression can interfere with the overall functioning of children and adolescents. It can impair normal cognitive and social development. The use of antidepressant medications in children and adolescents has grown in the past decade. Newer antidepressant agents, the selective serotonin reuptake inhibitors, appear very promising, but their safety and efficacy have not been established for children. This review focuses on depression and the design of studies for its treatment with newer antidepressant drugs in children. PMID- 7787938 TI - Renal toxicity of cancer chemotherapeutic agents in children: ifosfamide and cisplatin. AB - Ifosfamide and cisplatin are two commonly used cancer chemotherapeutic agents associated with significant acute and chronic renal toxicity. The clinical characteristics of ifosfamide-induced renal injury are proximal tubular wasting of glucose, phosphate, bicarbonate, sodium, potassium, and amino acids; proteinuria; and decreased glomerular filtration rate. Cisplatin administration may result in a dose-dependent reduction of glomerular filtration rate, hypomagnesemia, hypokalemia, and polyuria. The characteristics of renal toxicity associated with each of these agents are discussed with attention to possible mechanisms of injury and long-term clinical outcome. PMID- 7787939 TI - Therapy of pediatric AIDS. AB - Therapy of pediatric AIDS utilizes antiretroviral compounds; antibiotic, antifungal, and antiparasitic agents; and both active and passive immunization in a multifactorial approach. Currently, newly diagnosed pediatric AIDS cases are acquired predominantly through vertical transmission from HIV-infected mothers. Pediatric AIDS research is focused on strategies to prevent vertical transmission of HIV infection as well as therapy against opportunistic and progressive HIV disease. Zidovudine remains first-choice therapy for HIV infection and can reduce the rate of vertical transmission of HIV. Didanosine is also approved to treat HIV infection in pediatric AIDS. Other reverse transcriptase inhibitors are under investigation as alternative or combination therapies because of HIV resistance to zidovudine and didanosine. Alternative therapies for opportunistic infections are being investigated. Passive immunity with intravenous immunoglobulin is being reevaluated to determine efficacy in combination with other therapies. Finally, vaccination against usual childhood diseases with standard immunization schedules produces limited immunity, and alternative vaccination protocols warrant further investigation. PMID- 7787940 TI - Pharmacogenetics and development: are infants and children at increased risk for adverse outcomes? AB - Over the past two decades, pharmacokinetic data have clearly demonstrated that development can markedly influence the absorption, distribution, excretion, and metabolism of xenobiotics. With respect to many of the processes that govern drug metabolism, the underlying pharmacogenetic determinants that may control either the affinity or the capacity of a drug or toxicant substrate for the enzymes responsible for its biotransformation appear to be altered as a function of development by mechanisms that are, for the most part, not well defined. Nonetheless, for many xenobiotics, the pharmacogenetic-developmental interface produces a "pattern" for drug metabolism that, when characterized, supports the pharmacokinetic properties (eg, drug clearance) reported for many agents across the pediatric age spectrum. With the exception of a few relatively well characterized adverse drug effects (eg, toxicity of 6-mercaptopurine in patients with absent thiopurine methyltransferase activity, increased incidence of hepatotoxicity to valproic acid in young infants), the relationship of development and pharmacogenetics to enhanced toxicity risk from xenobiotic exposure is poorly defined. However, failure to adequately appreciate the pharmacokinetic consequences of the pharmacogenetic-developmental interface and to individualize therapy accordingly may lead to a clinically significant risk of drug therapy, namely, over- or underdosing. PMID- 7787941 TI - Child abuse, sudden infant death syndrome, and attention-deficit hyperactivity disorder. AB - A review of recent literature helps to clarify normal variations in the physical examination of children who are thought to have been sexually abused. In many instances, no abnormal physical findings are discovered. Clinicians must continue to pay careful attention to the history and work with other professionals to implement appropriate management, despite the lack of physical findings. Guidelines for evaluating sudden and unexpected infant deaths are reviewed. The current recommendations of the American Academy of Pediatrics for infant sleep positions are discussed in light of epidemiologic studies in the United States and other countries. Attention-deficit hyperactivity disorder appears to respond best to a combination of stimulant medication, parent training in coping with behavior of affected children, and social skill training for the affected children themselves. A review of recent research failed to reach consistent correlations between resistance to thyroid hormone and attention-deficit hyperactivity disorder. PMID- 7787942 TI - Dentate gyrus destruction and spatial learning impairment after corticosteroid removal in young and middle-aged rats. AB - We investigated the functional and behavioral implications of chronic corticosteroid removal in young and middle-aged rats. Prepubertal and 13-month old rats were adrenalectomized (ADX) or sham operated (SHAM). The young ADX rats were divided further into three groups: ADX with no hormone replacement, ADX given corticosterone chronically, (chCORT), and ADX given corticosterone acutely at the time of Morris water maze testing (acCORT). All rats were run on the Morris water maze 12 weeks after surgery. They were then sacrificed and the brains were removed for histological analysis. The results showed that prolonged corticosteroid absence caused major damage to the dentate gyrus and learning impairment on the Morris water maze. The chCORT rats had little dentate gyrus cell loss and were as efficient as the controls in Morris water maze performance, whereas the acCORT rats had dentate gyrus cell loss and were impaired in the spatial acquisition task. Furthermore, exogenously administered corticosterone had an interactive effect on ADX rats. Water maze performance was improved in dentate gyrus damaged rats (acCORT) compared to ADX rats not given corticosterone, whereas ADX rats with very little dentate gyrus damage (chCORT) did not exhibit better water maze performance relative to controls. Middle-aged ADX rats lost cells only in the dorsal blade of the dentate gyrus but they did not show a learning impairment in the Morris water maze relative to the middle aged controls. These results indicate that corticosteroids are trophic for the dentate gyrus, that mature granule cells are less affected by adrenalectomy, that corticosteroid absence is responsible for some water maze impairment in ADX rats, but that in addition to corticosteroid absence, a substantial amount of dentate gyrus damage is necessary to impair spatial learning. PMID- 7787943 TI - Interhippocampal synthesis of lateralized place navigation engrams. AB - Rats were trained in a water maze in a dark room with the extramaze cues restricted to only dimly back-lit shapes. We used lidocaine to reversibly lesion the dorsal hippocampus and this controlled-cue room in order to examine interhippocampal synthesis of lateralized place engrams. Experiment 1 showed that lidocaine injected into both hippocampi effectively abolished place navigation for up to 25 min but not at 45 min. In experiment 2, each day under lidocaine blockade of one hippocampus, pretrained rats were trained in the water maze to locate the target according to two cues (e.g., AB). Two hours later, the contralateral hippocampus was inactivated and the rats were trained to the same location with two other cues (CD). On day 5, intact brain retrieval was tested in one of three conditions: ACQ (e.g., AB), one of the pairs of cues used in acquisition training; SYNTH (e.g., AC), one cue from each of the pairs used in acquisition; CONT (e.g., AE), one cue that was used in acquisition training and a novel cue. The results show that the hippocampi learned the two tasks independently and similarly [latency (L) at the asymptote = 7 s]. Retrieval performance was at the asymptote for ACQ (AB) and SYNTH (AC) (L = 6 and 7, respectively) but was disrupted for CONT (L = 12). In experiment 3 as in experiment 2, the rats were trained, under unilateral blockade, to a new place for 4 days. On day 5, retrieval with the trained hippocampus blocked was worse (L = 11) than with the untrained side blocked (L = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787944 TI - Correlation of anoxic neuronal responses and calbindin-D28k localization in stratum pyramidale of rat hippocampus. AB - Immunohistochemical staining for the calcium-binding protein calbindin-D28k (CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the subiculum of rat hippocampal slices during brief exposure (4.0 +/- 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 +/- 2.79 mV above VM = -70.5 +/- 1.50 mV, n = 30 and -7.2 +/- 0.72 mV below VM = -68.2 +/- 1.34 mV, n = 24, respectively) and a fall in membrane resistance of approximately 20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin-negative (CaBP(-)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(-) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(-) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+ influx and may facilitate the movement of Ca2+ away from points of entry. The neurons which are CaBP(-), deep, and closer to subiculum and in which N2 evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+ which could activate K+ conductance, inhibit Ca2+ influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability. PMID- 7787945 TI - Activation of somatostatin-synthesizing neurons in the hippocampal formation through kindling-induced seizures. AB - The present study was designed to determine if and to what extent somatostatin (SST) synthesizing neurons of the hippocampal formation are activated during seizures, elicited through kindling of the perforant pathway. Tissue was used and analyzed from animals which had experienced a single after discharge, or a stage 3 or stage 5 seizure. The protein expression of the oncogene c-fos in activated, depolarizing neurons was utilized to identify seizure-activated SST-synthesizing neurons. Combined immunocytochemical and in situ hybridization methods were used to identify these double-labeled, Fos protein, and SST mRNA-containing neurons. The results were quantified and compared across seizure stages. The resulting data demonstrate that at every stage of seizure development, a majority of SST synthesizing neurons is activated, but that these activated SST mRNA-containing neurons represent only a minority of all seizure-activated, Fos-expressing neurons in the hippocampal formation. The data further reveal a numerical hierarchy in which the majority of double-labeled neurons is present in the hilus of the dentate, followed by the stratum oriens of CA1. It is concluded that SST synthesizing neurons represent an integral component of the kindling activated neuronal network and, since the SST synthesizing neurons represent the minority of all seizure-activated neurons in the hippocampal formation, that this neuronal network is likely to be of considerable neurochemical complexity. PMID- 7787946 TI - Reduction of the threshold for long-term potentiation by prior theta-frequency synaptic activity. AB - Activation of the lateral perforant path input to the dentate gyrus with theta patterned conditioning trains produced LTP of synaptic efficacy that changed in magnitude as an inverted U-shaped function of the number of trains. The LTP induction function was not fixed, however, and could be shifted to the left by administering 5 Hz "priming" stimulation to the lateral path 10 min prior to the conditioning trains. The priming effect was input specific and selective to a narrow window of stimulus frequencies. The shift to the left of the LTP induction function by priming stimulation was blocked by the muscarinic receptor antagonist atropine sulphate. Nimodipine, an antagonist of L-type voltage-sensitive calcium channels, did not mimic the priming effect but instead produced a general facilitation of LTP induction. These data demonstrate that the degree to which LTP is induced in the lateral path is a non-linear function of afferent activity, and that this function, including LTP threshold, can be shifted to the left by prior synaptic activity at hippocampal theta-rhythm frequencies. PMID- 7787947 TI - NADPH diaphorase-positive neurons in the lizard hippocampus: a distinct subpopulation of GABAergic interneurons. AB - We analyzed the distribution and light-microscopic features of the NADPH diaphorase-containing structures in the lizard hippocampus, likely to correspond to nitric oxide synthase-containing cells and fibers, and thus likely to release nitric oxide. We also studied co-localization of NADPH diaphorase with the neurotransmitter GABA, the calcium-binding protein parvalbumin, and the neuropeptide somatostatin, in order to examine whether putative nitric oxide synthesizing neurons represent a different subpopulation of GABA cells, on which the authors recently reported in lizards. We also studied co-localization of NADPH diaphorase with parvalbumin or somatostatin in mice to ascertain whether the characteristics of this population in reptiles parallel the situation in mammals. Most of the positive NADPH diaphorase neurons were stained in a Golgi like manner and were in the plexiform layers of the lizard hippocampus with morphologies ranging from bipolar to multipolar. Co-localization with GABA was 100%, and NADPH diaphorase-positive neurons in the lizard hippocampus did not contain parvalbumin or somatostatin. The results indicate that putative nitric oxide-synthesizing neurons represent a distinct subpopulation of GABA interneurons in the lizard hippocampus. Two different types of fibers were described in the plexiform layers: one type bearing thick varicosities, and the other thinner ones. We discuss the possibility that at least part of the positive fibers arise from a hypothalamic aminergic nucleus contacting the third ventricle, the periventricular hypothalamic organ. Most radial glia were stained almost completely and formed typical end-feet both at the pia and around capillaries. The results of this study confirm that the capacity for synthesizing nitric oxide is linked to a determined set of neuronal markers depending on the specific brain region, and they provide new resemblances between hippocampal regions in different classes of vertebrates. PMID- 7787948 TI - Adenosine antagonists have differential effects on induction of long-term potentiation in hippocampal slices. AB - How adenosine leakage and tetanic release might affect long-term potentiation (LTP) was investigated by applying adenosine antagonists 8(p sulfophenyl)theophylline (8SPT) or 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H purine-2,6-dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. In the presence of 8SPT--at concentrations (10-50 microM) which block both A1 and A2 receptors--the same tetani consistently evoked LTP of population spikes but not of excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A1 receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A1 receptors but on the other facilitates LTP via A2 receptors. In a second set of experiments, 8SPT (50-100 microM) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A2 receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP induction. PMID- 7787950 TI - Simultaneous blockade of non-NMDA ionotropic receptors and NMDA receptor associated ionophore partially protects hippocampal slices from protein synthesis impairment due to simulated ischemia. AB - A large body of evidence exists to demonstrate that excitatory amino acids (EAA) and their receptors are involved in the pathophysiological mechanisms linking several acute brain insults, such as cerebral ischemia, to neuronal degeneration and death. Accordingly, the use of EAA receptor antagonists can be beneficial in attenuating or preventing the neuronal irreversible damage subsequent to various neuropathological syndromes. We have investigated the effect of 15 min of simulated ischemic conditions, i.e., oxygen/glucose deprivation, on hippocampal slices preparation measuring, as neurotoxicity indexes, both the amino acids efflux in the incubation medium, detected by HPLC, and the inhibition of protein synthesis, evaluated as 3H-Leucine incorporation into proteins. Accumulation of neurotransmitter amino acids was measured in the medium during the "ischemic" period. Glutamate increased 30-fold over the basal level while aspartate was sevenfold and GABA 12-fold higher than in normal conditions. After a reoxygenation period of 30 min, the rate of protein synthesis of hippocampal slices subjected to "ischemia" was reduced to 35-50% of controls. The non competitive NMDA antagonist MK-801 (100 microM) and the competitive NMDA antagonist CGP 39551 (100-250 microM) as well as the non-NMDA receptor antagonists NBQX (100 microM) and AP3 (300 microM) were unable to counteract the metabolic impairment when they were present alone in the incubation fluid during simulated "ischemia." An incomplete, but highly significant (p < 0.001), protection from protein synthesis impairment was achieved in the presence of an equimolar concentration (100 microM) of MK-801 and NBQX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787951 TI - Regulation of penile venous outflow. Experimental studies on endogenous control mechanisms. PMID- 7787949 TI - Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells. AB - The cellular-synaptic generation of rhythmic slow activity (RSA or theta) in the hippocampus has been investigated by intracellular recording from principal cells and basket cells in anesthetized rats. In addition, the voltage-, coherence-, and phase versus depth profiles were examined by simultaneously recording field activity at 16 sites in the intact rat, during urethane anesthesia, and after bilateral entorhinal cortex lesion. In the extracellular experiments the large peak of theta at the hippocampal fissure was attenuated by urethane anesthesia and abolished by entorhinal cortex lesion. The phase versus depth profiles were similar during urethane anesthesia and following entorhinal cortex lesion but distinctly different in the intact, awake rat. These observations suggest that dendritic currents underlying theta in the awake rat may not be revealed under urethane anesthesia. The frequency of theta-related membrane potential oscillation was voltage-independent in pyramidal neurons, granule cells, and basket cells. On the other hand, the phase and amplitude of intracellular theta were voltage-dependent in all three cell types with an almost complete phase reversal at chloride equilibrium potential in pyramidal cells and basket cells. At strong depolarization levels (less than 30 mV) pyramidal cells emitted calcium spike oscillations, phase-locked to theta. Basket cells possessed the most regular membrane oscillations of the three cell types. All neurons of this study were verified by intracellular injection of biocytin. The observations provide direct evidence that theta-related rhythmic hyper-polarization of principal cells is brought about by the rhythmically discharging basket neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787952 TI - Private health insurance and a healthy personality: new risk factors for obstetric intervention? AB - In this study 242 nulliparous pregnant women completed standardized psychometric questionnaires and semi-structured interviews in the latter half of pregnancy and again 4-6 weeks postpartum. Discriminant function analysis revealed that the use of operative obstetric interventions was measurably influenced by psychosocial factors. Privately insured women were significantly more likely to experience instrumentally assisted (relative risk = 1.53, 95% CI: 1.05, 2.25) and Caesarean (relative risk = 1.91, 95% CI: 1.05, 3.46) deliveries than those receiving care in the public hospital system. The likelihood of experiencing these procedures was increased further among those who in late pregnancy were thinking clearly, had high self-esteem, mature means of dealing with anxiety, were confident in their knowledge of childbirth procedures and in secure partnerships with highly educated men. There was no evidence that either elevated anxiety or abnormalities of personality contributed to obstetric outcome. These findings indicate that obstetric decision-making is significantly influenced by patient personality and socioeconomic circumstances. In particular, they suggest that fear of malpractice litigation, physician convenience factors and the response of obstetricians to assured, well pregnancy-educated pregnant women may be influencing the use of operative intervention in delivery. PMID- 7787953 TI - Non-traditional mothers: single heterosexual/lesbian women and lesbian couples electing motherhood via donor insemination. AB - The purpose of the project was to explore the motivation, reproductive and postdelivery experiences, and future concerns of single heterosexual and lesbian women and lesbian couples who attempted conception via donor insemination (DI). All women who had completed at least one cycle of DI between 1987 and 1992 at a large medical school infertility program were mailed a comprehensive 'Motherhood' questionnaire. Forty-five women completed the survey (response rate = 88%) of whom 14 were lesbians, 28 were heterosexuals, two were bisexual and one was celibate. The only major differences between the heterosexual women and the lesbian women were that the heterosexual women were older and had started DI attempts at an older age than the lesbian women. The majority of women reported that four major considerations prompted their decision to initiate DI when they did: feeling secure in their employment, the sense that time was running out, feeling that they had 'worked through' concerns about parenting, and that they had sufficient social support. Three characteristics were deemed moderately or very important in their selection of sperm donors: ethnicity, education and height. After achieving a pregnancy, most women wished to know more detailed information about their donor. Unlike heterosexual couples, all single and lesbian women planned to disclose the fact of DI to their offspring but were uncertain of when or how to accomplish this. The greatest worry reported by respondents was how their child would deal with the absence of a known designated father. Overall, the women were gratified with their experience of DI, and the majority would 'absolutely' recommend it to a friend. PMID- 7787954 TI - Medical history in women with premenstrual syndrome. AB - This study was designed to identify significant factors in the medical history of women with premenstrual syndrome (PMS). Medical history variables of 190 women with PMS were compared with those of a group of 182 women without premenstrual symptoms who sought gynecological care (control group). All the participants were carefully selected by interview and designated questionnaires. Women with a past or present psychiatric history were excluded. The results showed that age, number of children, age of menarche, smoking history and family history of psychiatric disorders of the women with PMS and the controls were similar. Women with PMS exhibited a significantly greater frequency of postpartum depression (43% versus 12%), past birth control pill use (91.6% versus 45.9%), alcohol use (39.5% versus 14.8%) and drug use (48.4% versus 14.1%) than did the controls respectively; all p values were < 0.05). Our data suggest an association between these factors and PMS. They should be identified in women with premenstrual complaints during the initial visit, and the roles of these factors in the pathophysiology of PMS need to be further investigated. PMID- 7787955 TI - Premenstrual complaints: an idiosyncratic syndrome. AB - The two issues of premenstrual syndrome (PMS) symptom heterogeneity and symptom severity are addressed in an examination of the idiosyncratic nature of premenstrual complaints. Analyses of PMS symptoms reported during the first assessment month by a group of treatment-seeking women revealed that when presented with a prepared list of symptoms (Menstrual Distress Questionnaire), they select many more symptoms than when self-reporting their complaints in ranked order of severity. In this study of a sample of 98 women, most of the women reported only four rank-ordered symptoms. Symptom profiles from five symptom categories were constructed for each of the women and from a possible 86 different profiles 84 were discovered. Of these, psychological profiles dominated the total reports. These findings, together with results of previous research, lead to two conclusions. First, that PMS, though multidimensional, may be defined for each woman by a limited number of symptoms; and second, that PMS is highly idiosyncratic in nature. PMID- 7787956 TI - University students' subjective experiences of oral contraceptive use. AB - A substantial proportion of women who commence oral contraceptive discontinue usage due to unwanted side-effects. In investigations of side-effects in current users, such women are excluded, and hence such studies will tend to underestimate the prevalence of side-effects. One hundred and forty-five female university students (both former and current users) completed a questionnaire focusing on their experiences of the impact of oral contraceptives upon their psychological and physical well-being. Although, on average, over half the women reported no effect, the vast majority of those who did report a change in well-being deemed this to be negative. The only exception was pelvic pain which was reported to be improved by oral contraceptive use. PMID- 7787958 TI - Public reporting of performance measures in home care. AB - BACKGROUND: In 1992 DependiCare Home Health, Inc (Broadview, Ill), a 62-employee home medical equipment/respiratory therapy (HME) business in the Chicago metropolitan area, discovered that managed care organizations need quantifiable data from vendors in the form of measurements or outcomes. In response to this need, DependiCare developed its "Under the Microscope" program. This program provides quarterly reports (starting in April 1994) on service efficiency, patient satisfaction, and outcome statistics to referral sources, including physicians, discharge planners, and hospital executives. MEASUREMENTS: Performance measures, which represent information from DependiCare's internal operations, can be viewed as the company's quarterly report card. Areas reported on include target-time performance, same-day and under-two-hour delivery, patient (and referral source) satisfaction, equipment breakdown, and fillrate statistics. Outcome statistics include discontinuation of service by diagnosis and number of months on oxygen by diagnosis. USE OF RESULTS: Measurements help to identify weaknesses that need to be addressed by organizational or operational changes, as well as to uncover strengths that can be capitalized on for sales and marketing. Hospital-based discharge planning departments, a substantial referral source, most often use the Under the Microscope program to justify referring patients to DependiCare. Little is known about managed care customers' use of the data. CONCLUSIONS: In the long term, an integrated, automated way to track individual patients across the continuum of care from the physician, to the hospital, and to home care is needed. A centralized database of patient experience, including outcomes, could assist in health care decision making. PMID- 7787957 TI - Prognostic factors for preoperative consultation of women desiring sterilization: findings of a retrospective analysis. AB - In this exploratory study, 37 sterilized women applying for sterilization reversal were questioned thoroughly to establish why they had decided to undergo sterilization and why they now wished for it to be reversed. Taking an interactive behavioral model as our starting point, we concentrated on the psychosocial circumstances leading to the definitive decision to be sterilized. A relationship crisis at the time of sterilization was found to be a prognostically unfavorable factor. Furthermore, 20 of the 37 patients cited new partnerships as their main reason for seeking reversal. Those who felt pressurized by their gynecologist or partner into undergoing sterilization had significantly more problems in overcoming the psychological stress accompanying such an operation than those who, through a series of consultations on contraception, had had sufficient time and opportunity to make their own decisions. Sterilization performed for medical reasons was found to have particularly problematical consequences, especially where the doctor had made the decision largely on his own, failing to give an adequate explanation for the medical necessity of the operation. Regarding the time chosen for sterilization, the study revealed that the patient's postoperative psychological condition was significantly worse when sterilization was carried out immediately after a delivery, after abortion or after Caesarean section, rather than in the interval between pregnancies. The resulting increase in the incidence of psychosomatic complaints and depressive states is also confirmed in the literature. The findings of this study offer practical suggestions for improved preoperative consultation and should help to determine the course of action to be taken when a patient wishes to be sterilized. PMID- 7787959 TI - Computer-assisted quality improvement in an ambulatory care setting: a follow-up report. AB - BACKGROUND: The Quality Care Program (QCP), introduced into the Swedish Family Medicine Clinic in 1992, is a comprehensive computer-assisted program of quality improvement for the medical office. Its goal is to improve specific aspects of ambulatory patient care: disease prevention, cancer detection, immunization compliance, risk management, outcomes monitoring, and patient education. METHODOLOGY: The QCP uses a computer-generated worksheet that is attached to the medical record at each patient visit. It is a multipurpose worksheet that displays important clinical information and functions as part of an overall strategy to manage key aspects of the patient's care. The system enhances patient and physician performance of health maintenance and continuity of care, and it allows for the quantification and display of performance indicators without exclusive reliance on chart review. RESULTS: Physician reliability in recommending health maintenance interventions has improved to nearly 100%, and patient compliance with these recommendations has significantly increased. The test results tracking system has found test data that would have otherwise been lost, and the outcomes monitoring has resulted in measurable system improvements. There has been a modest increase in provider workload to meet these aggressive QCP goals, but measures of provider satisfaction have increased nonetheless. CONCLUSIONS: Ambulatory care, increasingly the focus of attention in the United States, can be difficult to perform well. The QCP, part of an overall quality improvement initiative, gathers and displays clinical information, reminds patients and physicians to do health maintenance, and refuses to let physicians and patients forget about specific aspects of patient care. PMID- 7787960 TI - Ombudsmen, patient complaints, and total quality management: an examination of fit. AB - BACKGROUND: In response to mounting health care costs in the United States and Canada, there is considerable national discussion of health care quality, including the importance of assessing and monitoring patient satisfaction and of responding to complaints. Many physicians and health care administrators cringe at the mention of using patient complaints and satisfaction levels as quality measures; others perceive the need to develop multiple source indicators of patient care. At the same time, leaders are seeking programs and methods that contribute to the continuous improvement of all aspects of health care organizations. DISCUSSION: The use of patient ombudsmen and patient complaints in quality management programs is reviewed and the relation between the two functions--ombudsmen/complaint handling and total quality management--is discussed. Purposes, objectives, problem-solving processes, program operations, data use, and the outcomes of ombudsmen efforts are reviewed. Since ombudsmen programs value patient feedback, empower customers, and help contribute to the diagnosis of organizational areas for improvement, they are consistent with the intent and workings of quality teams. The activities of ombudsmen can contribute to the broader effort to manage the whole organization toward the continuous improvement of quality. PMID- 7787961 TI - Ending the QA/CQI confusion. Interview by Steven Berman. PMID- 7787962 TI - Psoriatic arthritis. PMID- 7787963 TI - Intravenous immunoglobulin therapy. PMID- 7787964 TI - Orthotic treatment of the hand. What's new? AB - Keeping abreast of the latest orthotic products is challenging. Commercial orthoses need to be critically evaluated for their applicability to the person with rheumatic disease. Custom-made orthoses play an invaluable role in achieving a wide range of therapeutic goals: improving function and pinch, stabilizing individual joints, preventing positional contractures, protecting joints from trauma, stretching the intrinsic muscles, correcting joint- and soft-tissue contractures, and controlling inflammation. PMID- 7787965 TI - Kinetics of irreversible inhibition of creatine kinase during modification by o phthaldehyde. AB - It has been previously reported that, with a fluorescence probe formed from o phthaldehyde (OPTA) and the thiol and amino groups at or near the active site of creatine kinase, inactivation and exposure of the probe take place simultaneously and well before unfolding of the molecule as a whole. In this study, the inactivation and modification kinetics of purified rabbit muscle creatine kinase by OPTA have been compared, the former by following the substrate reaction in the presence of a previously described inactivator. The microscopic rate constants for the reaction of the inactivator with the free enzyme and with the enzyme substrate complexes were determined. From the results obtained it appears that OPTA is noncompetitive with respect to both substrates. The inactivation kinetics is monophasic with OPTA, and neither ATP nor creatine alone affect the rate constant of inactivation of the enzyme, indicating that the irreversible inhibition of creatine kinase by OPTA is of the noncompetitive type. PMID- 7787966 TI - A sensitive enzyme-linked immunosorbent assay of serum ornithine carbamoyltransferase. AB - Ornithine carbamoyltransferase (OCT), a urea cycle enzyme, is located almost exclusively in liver mitochondria. We designed a sensitive enzyme-linked immunosorbent assay (ELISA) of serum OCT protein using an antibody against purified bovine enzyme. OCT protein measured using this method showed a good correlation with OCT activity (r = 0.961), and was much higher in patients with liver diseases than in the controls. Measurements of serum OCT protein in 442 healthy blood donors gave the upper limit of normal range of 23 ng Eq/ml (equivalent to the bovine enzyme) for males, 8 ng Eq/ml for females, and 16 ng Eq/ml for males plus females. The values differ significantly between the sexes and depending on ages. This ELISA system is expected to be used as a pertinent liver function test. PMID- 7787967 TI - Clinical evaluation of serum ornithine carbamoyltransferase by enzyme-linked immunosorbent assay in patients with liver diseases. AB - We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for serum ornithine carbamoyltransferase (OCT) protein, and examined serum OCT concentrations in patients with various liver diseases. OCT concentrations were markedly elevated in cases of hepatic encephalopathy, 'acute on chronic', and those with the acute phase of acute hepatitis, moderately in chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis, and slightly in those with a fatty liver. High percentages (92-98%) of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma had higher than normal concentrations of serum OCT protein. There was a close correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and moderate correlations with those of mitochondrial AST, glutamate dehydrogenase and gamma-glutamyltranspeptidase. The OCT/ALT ratio was higher in patients with liver cirrhosis than in those with chronic hepatitis (p < 0.001), and was still higher in cases of hepatocellular carcinoma (p < 0.05). In 2 patients with 'acute on chronic' disease, OCT concentrations decreased similarly with or more rapidly than AST or ALT activities after admission. In 2 patients with hepatic encephalopathy, the OCT concentrations changed similarly with AST and ALT activities. This OCT ELISA system will aid in diagnosing various liver diseases and in the follow-up of the patients, and the OCT/ALT ratio may serve for a differential diagnosis of liver diseases. PMID- 7787968 TI - Structural characterization of cytosolic NADP(+)-dependent isocitrate dehydrogenase from rat ovary. AB - Cytosolic NADP(+)-dependent isocitrate dehydrogenase was purified to homogeneity from superovulated rat ovaries. Amino acid sequence information was obtained by analyzing peptides generated by digestion with either cyanogen bromide or trypsin. Eleven peptides were sequenced and a total of 146 amino acids were identified. Nine of these peptides were found to be 60-100% identical with sequences from mitochondrial NADP(+)-dependent isocitrate dehydrogenase. Conservation of amino acids was observed for residues that were previously identified as potentially binding isocitrate-Mg2+. Circular dichroism measurements showed that the structure is composed of approximately 35% alpha helix and 21% beta-sheet segments. Temperature denaturation studies indicated that the enzyme is more stable in the presence of isocitrate. PMID- 7787969 TI - Induced expression of alpha-enolase in differentiated diffuse large cell lymphoma. AB - A unique protein has been detected that is associated with the differentiation of diffuse large cell lymphoma (DLCL). The WSU-DLCL human cell line was cultured in the absence or presence of the biological agent, Bryostatin 1 (Bryo1). Cellular proteins of parent and differentiated WSU-DLCL cells were analyzed using one- and two-dimensional polyacrylamide gel electrophoresis (1D and 2D PAGE). In the 1D PAGE, a unique protein band of molecular mass approximately 47 kD was detected in the differentiated, but not the parent cells. Amino acid sequence of the band indicated the presence of more than one protein. The 2D PAGE analysis showed that one of the proteins of interest had an isoelectric point of 7.4. Partial amino acid sequencing of the spot by tryptic digest showed 100% homology with alpha enolase. alpha-Enolase is a nonneuronal enzyme involved in the glycolytic pathway. This is the first report on the induction of alpha-enolase in human DLCL after treatment with the natural biological agent, Bryo1. We suggest that alpha enolase may play a significant role in the differentiation of lymphoma in man. PMID- 7787970 TI - Purification of human and rat kidney aldose reductase. AB - In the present study we report on a rapid two-step affinity chromatographic procedure to purify aldose reductase from human and rat kidney papilla and inner medulla. This enzyme, which is responsible for sorbitol formation in the kidney, was purified 145-fold from rat and 76-fold from human kidneys by consecutive Blue Sepharose and Matrex Orange chromatography. SDS-PAGE showed a single band of 38 kD for the human enzyme and a doublet of similar molecular weight for the rat kidney aldose reductase. The enzyme was characterized by substrate specificity and kinetic constants found identical to that of other organs purified previously. PMID- 7787974 TI - Distal tibia bone graft for arthrodesis of the foot and ankle. AB - Forty patients since 1988 have had distal tibial bone grafting for 41 arthrodeses of the foot and ankle. Bone graft is obtained through a cortical window made just above the medial metaphyseal distal tibial flare. Average follow-up was 23.3 months. Forty of 41 arthrodesis sites fused; there was only one nonunion. There were no delayed unions. There were no complications at the donor site based on patient examination and radiographs. Ipsilateral ankle motion was not affected by the bone graft procedure. Cited complications from iliac crest bone graft include donor site pain, blood loss, heterotopic bone formation, pelvic instability, iliac hernia, infection, fracture, and deformity. Complications with allografts include disease transmission and immune response. These are avoided by using locally obtained distal tibia autograft for arthrodeses in the foot and ankle. PMID- 7787973 TI - The short oblique fracture of the distal fibula without medial injury: an assessment of displacement. AB - Eighteen patients with ankle injuries presenting as short oblique fractures of the distal fibula with no clinical or radiographic evidence of injury to the medial ankle were studied for fracture displacement. Plain radiographs and computed tomography were used for analysis. All fractures were clinically diagnosed as supination-external rotation stage 2 (SE-II) injuries under the Lauge-Hansen scheme. All exhibited slight displacement on plain radiographs and were treated nonoperatively. Computerized tomography using axial cuts across the fracture site and ankle mortise revealed normal positioning of the talus beneath the tibial plafond, as evidenced by no abnormality of the medial joint space in all patients. In the majority of patients, the relationship between the talus and distal fibula also appeared undisturbed, with fracture displacement being confined to a change in position of the proximal fibular fragment relative to the tibia as compared with the contralateral ankle. In a minority of cases, in addition to the above-described displacement of the proximal fibular fragment, the distal fibular fragment was noted to shift slightly laterally relative to the talus, with mild widening of the lateral joint space. Occult-associated avulsion fractures off the distal tibia were present in 39% of the cases. PMID- 7787971 TI - Effect of grape seed tannins on the activity of some rat intestinal enzyme activities. AB - The present study was designed to investigate the effects of grape seed tannins on rat intestinal alkaline phosphatase (AP), sucrase and dipeptidyl peptidase IV (DPP IV) activities. An experiment was performed in vivo by dietary supplementation with 2% tannins; this diet was tested on an experimental group of rats; a control group received a diet without tannins. After 31 days, tannins intake significantly decreased middle-jejunal AP from 123 to 45 mU/mg protein and sucrase activities from 310 to 195 mU/mg protein, while no significant difference appeared at the duodenal stage (p < 0.05). Ileal DPP IV activity was also significantly reduced (p < 0.05) from 190 to 110 mU/mg protein after tannin intake. Using in vitro experiments on purified brush border membranes, AP activity was found to be inhibited by grape tannins; this inhibition was prevented by the detergent Triton X-100. The addition of pancreatic-biliary (PB) juice to the incubation medium prevented or reversed the tannin-inhibited enzyme activity. The present data indicate that in the duodenal lumen, alkalinity and detergency from the PB secretion neutralized the ability of tannins to inactivate brush border hydrolase activities and suggest that enzyme inhibition took place once bile salts were reabsorbed while moving down the gut. This was confirmed by in vitro experiments where sucrase and DPP IV activities inhibited by grape seed tannins were largely recovered after the addition of PB juice to the incubation medium. PMID- 7787975 TI - The strength of Achilles tendon repair: an in vitro study of the biomechanical behavior in human cadaver tendons. AB - Eighteen fresh frozen human Achilles tendons were used to test the ultimate strength of repaired tendon "ruptures." Three methods, the Kessler, the Bunnell, and the locking loop, were used to test the initial strength of Achilles tendon repair. The Kessler and Bunnell methods are current standard clinical configurations described for Achilles tendon repair. Under uniform and standardized laboratory conditions, the specimens were loaded to failure. The locking loop suture method was substantially stronger than either of the other two standard configurations. The latter two did not differ significantly from each other. The results of this study may be clinically relevant in terms of the choice of the repair method for surgically treated Achilles tendon ruptures. PMID- 7787972 TI - Hallux valgus correction using a modified Hohmann technique. AB - In 181 patients presenting with hallux valgus (247 toes), we performed a modified Hohmann procedure with Kirschner wire fixation of the osteotomy. Follow-up by a questionnaire was possible in 159 patients representing 217 operated toes (21 reoperations), and roentgenograms of bony healing were assessed in all these patients. The questionnaire was returned by 91% (145/159) of the patients. The average observation time was 52 months (25-97 months). The average correction of the hallux valgus angle was 10 degrees, ranging from 31.4 degrees before surgery to 21.4 degrees after surgery. Eighty-eight percent of the patients stated that they had an excellent or good/fair result, and 12% had pain or problems with footwear. We found a positive correlation among the correction of the valgus angle, the lateral displacement, shortening of the first metatarsal, and the overall result. No correlation was found among the plantar displacement, correction of the intermetatarsal angle and the result. The modified Hohmann procedure is, in our opinion, a safe and reliable procedure for treating hallux valgus deformity of the foot. PMID- 7787976 TI - Distraction osteogenesis for congenitally short lesser metatarsals. AB - Six lesser metatarsal lengthening procedures were performed in three patients using a miniature external fixator to perform distraction osteogenesis. The metatarsals were lengthened an average of 15.5 mm. The external fixator was left in place for an average of 15.5 weeks, with additional time in a cast or cast shoe. Complications included five occurrences of infection, two cases of premature healing of the osteotomy, one nondisplaced fracture through the new bone formation, and hypertrophic granulation at a pin site. While all metarasals were successfully lengthened, two rays (one patient) had symptomatic stiffness at the metatarsophalangeal joint with continued metatarsalgia. PMID- 7787977 TI - Gait analysis of the donor foot in microsurgical reconstruction of the thumb. AB - Clinical and step evaluations by a piezoelectric system board were performed in 54 patients who underwent microsurgical reconstruction of the thumb by great or second toe transfer. Forty-four patients were male and 10 were female. In 13 cases, the thumb was reconstructed by the Morrison wrap-around technique. In 27 cases, an extended variant of the Morrison technique was used in which the whole distal phalanx was harvested with skin and nail apparatus. Four patients were treated by great toe transfer and 10 were treated by second toe transfer. Follow up ranged from 2 to 144 months. The group of patients treated by the wrap-around technique presented hallux rigidus in 38.5% of cases. The group of patients treated by the extended variant of the Morrison technique presented a lesser tendency to hallux rigidus but a clear reduction of the pushing phase of hallux. The group of patients treated by second toe transfer presented a third and fourth metatarsal bone overload that was confirmed by a statistical Wilcoxon test: overload was linked to a plantar hyperkeratosis at the third metatarsal (20%), fourth metatarsal (10%), or fifth metatarsal bone (20%). A claw deformity of the third and fourth toes was observed in 20% of these patients. The four patients who underwent microsurgical reconstruction of the thumb by great toe transfer exhibited an overload of central and lateral metatarsal bones. Second toe transfer is not associated with the functional or cosmetic changes seen in great toe transfer and is therefore preferred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787978 TI - Fibular osteochondroma presenting as chronic ankle sprain. AB - A 19-year-old baseball player was referred for assessment of recurrent sprains of the right ankle. This was found to be secondary to a palsy of the common peroneal nerve that was compressed by an osteochondroma of the fibular neck. The lesion was resected from the fibula and the patient made a complete recovery. We present this case as an example of a rare underlying problem in a patient who was initially diagnosed as having a sports-related ankle injury. PMID- 7787979 TI - Idiopathic hallux varus. PMID- 7787980 TI - Arthroscopic removal of an osteoid osteoma of the talus: a case report. AB - This article describes a patient with a 10-year history of persistent ankle pain. Differential diagnosis included osteoid osteoma and anterior ankle impingement. This patient subsequently underwent arthroscopic excision of a lesion on the talar neck following a complete radiographic work-up, which was nondiagnostic. The diagnosis of osteoid osteoma was finalized upon pathologic study of the arthroscopic shavings. The use of a motorized instrument for excision did not preclude pathologic evaluation of the specimen. Therefore, in an accessible location on the talar neck, arthroscopic excision of an osteoid osteoma can be performed. PMID- 7787981 TI - Salter-Harris type IV epiphyseal fracture of the proximal phalanx of the great toe: a case report. AB - Epiphyseal fractures account for about one fifth of pediatric fractures. Approximately 10% cause major growth disturbances, depending on the location and type of the fracture and the skeletal maturity of the child. Intraarticular Salter-Harris type IV fractures are rare, carry a poor prognosis, and almost always need surgical reduction to prevent deformity. We present a case report of a pediatric patient who returned to normal function after the successful surgical reduction of a Salter-Harris type IV fracture in the proximal phalanx of the great toe. PMID- 7787982 TI - Spindle cell lipoma of the foot: a case report and literature review. AB - Lipomas are among the most commonly encountered soft tissue tumors in clinical practice, though they are rare in the foot. Although a presumptive diagnosis is typically made clinically, those tumors with atypical clinical features may require radiological consultation. Difficulty arises when radiographic features are not typical of lipoma. We present a fatty soft tissue tumor of the foot with nonadipose elements on magnetic resonance imaging evaluation. Differentiation of lipoma variants (e.g., spindle cell lipoma, atypical lipoma, pleomorphic lipoma, lipoblastoma, angiolipoma) from liposarcoma based on imaging features is not possible, necessitating surgical resection for definitive histological diagnosis. PMID- 7787983 TI - Partial rupture of the flexor hallucis longus tendon in a tennis player: a case report. AB - A 39-year-old woman sustained a forced dorsiflexion injury to the left great toe while pivoting to the right during tennis activity. Posteromedial ankle pain was reproduced with active plantarflexion and passive dorsiflexion of the great toe and, to a smaller extent, the lesser toes. Symptoms persisted for 9 months despite nonoperative treatment. Magnetic resonance imaging 5 months after injury revealed evidence of fluid surrounding the flexor hallucis longus (FHL) tendon. Operative findings 9 months after injury included scar tissue and tenosynovitis of the FHL and flexor digitorum longus tendon sheaths, with impingement of distal FHL muscle fibers and a longitudinal split tear (partial rupture) of the FHL tendon. Tenolysis, tenosynovectomy, excision of the distal muscle fibers, and repair of the partial tendon rupture were performed, resulting in resolution of symptoms. Partial rupture of the FHL tendon as a single-impact injury, or in activity other than ballet, has not been documented previously. PMID- 7787985 TI - A modified Keller resection arthroplasty. PMID- 7787984 TI - Hallux flexion deformity secondary to entrapment of the flexor hallucis longus tendon after fibular fracture. AB - This article presents a case of entrapment of the flexor hallucis longus tendon after open reduction and internal fixation of a Weber C ankle fracture resulting in interphalangeal joint contracture of the hallux. Pathology involving other tendons at the foot and ankle associated with ankle fractures is reviewed. Other scenarios of flexor hallucis longus pathology are discussed. Flexor hallucis longus anatomy, as related to distal fibular fractures, is outlined, and a recommendation is made to consider flexor hallucis longus entrapment as a cause of hallux dysfunction after open reduction and internal fixation of an ankle fracture. PMID- 7787986 TI - Aiming guide for accurate placement of subtalar joint screws. AB - Accurate placement of rigid fixation of the subtalar joint in arthrodesing procedures (triple, subtalar, or pantalar arthrodesis) can be difficult. We have found that the "bottom-up" method simplifies this procedure and eliminates many potential problems. A technique is described incorporating the bottom-up method utilizing the combined aiming device (Synthes, Paoli, PA). PMID- 7787987 TI - Small hepatocellular carcinoma: its relationship to multistep hepatocarcinogenesis. AB - Recent advances in imaging techniques have led to the discovery of small hepatocellular carcinomas (HCC). The small HCC most often exhibit low-grade malignant (LGM) or extremely well differentiated features, which are different from those of advanced, full-blown HCC. The LGM-HCC present a serious diagnostic challenge to pathologists and must be differentiated from benign (reactive) and atypical (borderline) hyperplastic nodules. Analysis of small HCC revealed that hepatocarcinogenesis frequently occurs stepwise from atypical hyperplasia to LGM HCC and subsequently to advanced HCC. The HCC arise in irregular regeneration in chronic liver disease and in the essentially normal liver after steroid administration. Although the tumor suppressor gene, p53, is revealed to be often mutated in advanced HCC, the genetic events corresponding to each stage of multistep hepatocarcinogenesis are not clarified at all. PMID- 7787988 TI - Immunohistochemical detection of macrophage-derived foam cells and macrophage colony-stimulating factor in pulmonary atherogenesis of cholesterol-fed rabbits. AB - In order to investigate the role of monocyte/macrophages and their relationship to the expression of macrophage colony-stimulating factor (MCSF) in pulmonary atherosclerosis, lungs were excised from rabbits that had been fed for 60 and 90 days on a diet containing 0.5% cholesterol. In the lungs, fatty streaks and elevated foam cell lesions predominated in the large or medium-sized elastic pulmonary arteries, while massive accumulation of foam cells in the intima of muscular arteries produced marked luminal narrowing and nearly complete occlusion. In these lesions, most of the foam cells were reactive with RbM2, a monoclonal antibody (mAb) against rabbit macrophages, while smooth muscle cell derived foam cells were detected by mAb against smooth muscle actin in the deeper area of elevated foam cell lesions of elastic arteries. Ultrastructural observation confirmed the presence of monocytes in the intima, their differentiation into macrophages, and their transformation into foam cells in the atherosclerotic lesions. Immunohistochemical expression of MCSF was demonstrated in the endothelial cells, smooth muscle cells and foam cells. A minor macrophage derived foam cell population was demonstrated to possess a proliferative capacity. These data suggest that MCSF is involved in the differentiation of monocytes into macrophages, their transformation into foam cells, and their proliferation during pulmonary atherogenesis. PMID- 7787989 TI - Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat. AB - Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM 1) monoclonal antibody prior to allotransplantation. In the two strain combinations examined, LEF-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft loss was the result of frequent occurrence of necrotizing arteritis within the grafts. In contrast, TO-to-WKAH transplants resulted in no change in graft survival and no arteritis. Necrotizing vasculitis in the LEJ-to-WKAH grafts was characterized by fibrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab1)2 form of anti-ICAM-1 antibody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-ICAM-1 antibody administration combined with lipopolysaccharide, Poly(I)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc mediated and Fc-independent mechanisms, depending on the donor-to-host combination. PMID- 7787990 TI - Transferrin receptor distribution and iron deposition in the hepatic lobule of iron-overloaded rats. AB - Under the condition of obvious iron-overload, there is a zonal hemosiderin (iron) deposition in hepatic lobules. The deposition is heaviest in the periportal (zone 1) and lightest in the perivenous (zone 3) hepatocytes. However, the mechanism for this pattern of iron deposition is obscure. Hepatic tissues from control, iron-deficient or iron-overloaded Wistar rats were used to study its pathogenesis. Iron-deficiency was induced by a low iron regimen. Iron-overload was produced by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe(3+)-NTA) for 1-4 months. Liver tissues of the rats were immunohistochemically and histochemically stained for transferrin receptor (TfR), transferrin (Tf), ferritin (Ft), and iron. The staining intensity of TfR, Tf and Ft increased in hepatocytes of iron-deficient rats and decreased in that of the iron-overloaded in comparison with the control rats. TfR staining was strong in zone 1, with gradual transition into weak staining in zone 3 hepatocytes of the rat liver. TfR located primarily on the hepatocyte membrane. Tf had both membranous and cytoplasmic distribution. Many hepatocytes in group B had strong cytoplasmic Tf staining. Conversely, only a few hepatocytes had weakly stained cytoplasmic Tf in group C. Hepatocytes and Kupffer cells were Ft positive in control rats. Ft was distributed only in the cytoplasm. The staining intensity of Ft was stronger in zone 3 than in zone 1 hepatocytes of iron-deficient rats. In iron-overloaded rats, the iron deposition was severe in zone 1 and mild in zone 3 hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787991 TI - Saikosaponin A-induced cell death of a human hepatoma cell line (HuH-7): the significance of the 'sub-G1 peak' in a DNA histogram. AB - Saikosaponin A (SSA) induced cell death in the human hepatoma cell line (HuH-7) was investigated. Shortly after exposure to SSA, a DNA histogram showed a 'sub-G1 peak', which was recently reported as suggestive of apoptosis by other researchers. However, the electrophoresis of DNA indicated that such was not the case in the present experiment. The decreased intake of rhodamine 123 and the swelling of mitochondria were remarkable shortly after SSA exposure. These data seem to support the idea that the sub-G1 peak represents necrosis rather than apoptosis. Interestingly, the DNA electrophoresis revealed the smear pattern of small DNA fragments shortly after SSA-exposure, although it did not show the apoptotic ladder pattern. This finding and the appearance of the 'sub-G1 peak' is thought to have been a result of the degradation of the nuclear DNA in the early stages of cell death. Because these findings are different not only from apoptosis, but also from typical necrosis, a distinct mechanism of cell death caused by SSA is suggested. PMID- 7787992 TI - Antigenicities of enteropathogenic Escherichia coli, lysozyme, and alpha-1 antichymotrypsin on macrophages of genitourinary malacoplakia. AB - Seven cases of genito-urinary malacoplakia were analyzed histologically, ultrastructurally and immunohistochemically in a comparison with two cases of xanthogranulomatous pyelonephritis. Immunohistochemically, von Hansemann cells and Michaelis-Guttmann bodies, both hallmarks for the diagnosis of malacoplakia, showed a common antigenicity for enteropathogenic Escherichia coli as cytoplasmic granules of varying sizes. These microscopic manifestations corresponded ultrastructurally to a series of phagolysosomal degradations of coliform bacilli. Serogroups against E. coli OK antigens, which were positive for malacoplakic cells, were not confined to a particular group. Macrophages of xanthogranulomatous pyelonephritis did not show the E. coli antigenicity. Antigenicity of lysozyme and alpha-1-antichymotrypsin on the von Hansemann cells was equivocal, but these enzymes were strongly positive on macrophages of xanthogranulomatous pyelonephritis. The macrophages of both malacoplakia and xanthogranulomatous pyelonephritis were positive for antihuman macrophage antibody. These results indicate that malacoplakia depends mainly on infection by a non-specific strain of enteropathogenic E. coli and may arise from defective digestive enzyme activity of infiltrating macrophages. Immunohistochemical analysis using antisera against E. coli OK antigens, lysozyme and alpha-1 antichymotrypsin was useful in identifying the prediagnostic stage of malacoplakia and in differentiating the lesion from xanthogranulomatous pyelonephritis. PMID- 7787993 TI - Interphase cytogenetics of gastric carcinoma: fluorescence in situ hybridization (FISH) applied to cells obtained from formalin-fixed paraffin-embedded tissues. AB - The interphase cytogenetics in formalin-fixed and paraffin-embedded gastric cancer tissues were examined by fluorescence in situ hybridization (FISH) with alpha-satellite DNA probes. Two gastric carcinoma cell lines, TMK-1 and MKN-28, were first analyzed cytogenetically. Of 25 TMK-1 cell karyotypes, chromosome 7 showed trisomy and chromosome 17 showed disomy in 18 cells. Most MKN-28 cells showed disomy of both chromosomes 7 and 17. Suspensions of singly isolated TMK-1 and MKN-7 cells were obtained from the cultured cells, and from paraffin-embedded tissue specimens fixed with formalin for 0, 1, 3 and 5 days obtained from xenotransplanted tumors in nude mice. The numbers of chromosomes 7 and 17 analyzed with the karyotypic preparations coincided well with those determined by FISH, even in the paraffin-embedded specimens. The number of tumor cells showing no signals, however, increased in the specimens after 5 days formalin fixation. In 10 surgically removed gastric carcinomas, the predominant signal number for chromosomes 7 and 17 in the cells of paraffin-embedded tissues was two (disomy), except in one papillary carcinoma, which was trisomic for chromosome 7. Large subpopulations (more than 20%) showing trisomy were found in four cases for chromosome 7 and in five cases for chromosome 17. A higher frequency of trisomy was found in well differentiated than in poorly differentiated carcinomas. These findings suggest that the FISH technique is a useful tool for detecting chromosomal aberrations in gastric adenocarcinoma cells, even in paraffin embedded specimens, as long as the tissues are fixed with formalin for an appropriate time. PMID- 7787994 TI - Mucin antigens expression and Ki-67 labeling in breast cancer: the peculiarity in scirrhous carcinoma. AB - The expression of mucin-related antigens (Tn, T, Sialosyl-Tn [STn], DF3 [mammary type apomucin related antigen], and intestinal-MRP [intestinal-type apomucin related antigen]) as well as Ki-67 labeling was examined in 58 mammary invasive ductal carcinomas (IDC) divided into 26 scirrhous subtype (SC) and 32 non scirrhous subtype comprising papillotubular carcinoma and solid-tubular carcinoma (PT-ST). These data were analyzed in connection with the various pathological prognostic factors such as nodal status, tumor size, estrogen receptor status and histological grading of carcinomas. The results were as follows: (a) in SC, the expression rate of Tn was significantly higher in the cases with positive lymph node metastasis or with large tumor size (> 2 cm) than in those with negative lymph node metastasis or with small tumor size (< or = 2 cm); (b) in PT-ST, the expression rate of STn was higher in the cases with positive lymph node metastasis or with large tumor size than in those with negative lymph node metastasis or with small tumor size; (c) in SC, Ki-67 labeling was significantly higher in the cases with positive lymph node metastasis than in those with negative lymph node metastasis; and (d) in PT-ST, Ki-67 labeling was lower in the cases with positive lymph node metastasis than in those with negative lymph node metastasis. In conclusion, Tn antigen expression was correlated with pathological prognostic factors in SC but not in PT-ST, whereas STn antigen expression was correlated with pathological prognostic factors in PT-ST but not in SC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7787995 TI - Adrenocorticotropic hormone-independent bilateral macronodular adrenocortical hyperplasia associated with Cushing's syndrome. AB - A case of adrenocorticotropic hormone independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is reported. A 59 year old male was admitted to hospital because of hypertension. Subsequently, hypercortisolism, low plasma adrenocorticotropic hormone (ACTH), loss of diurnal rhythm of ACTH, lack of suppression with high dose dexamethasone were found and bilateral adrenal enlargement was detected by abdominal computerized tomography and adrenal scintigraphy. Bilateral total adrenalectomy was performed under a diagnosis of bilateral adrenal hyperplasia associated with Cushing's syndrome. Both adrenal glands were enlarged in size and weight. Bulging nodules were found at the cut section. Microscopically, a variegated histologic pattern including trabecular, adenoid and zona glomerulosa-like (ZG-like) structures was revealed in the nodules. Immunohistochemical examination disclosed positive staining of cytochrome P-450 17 alpha, negative of 3 beta-HSD in the ZG-like structure. Ultrastructurally, the cells composing the ZG-like structure were similar to those of the ZG in normal adrenal cortex. The authors agree that AIMAH is one of the entities causing Cushing's syndrome, and advise pathologists to keep this disorder in mind when they examine the adrenals in Cushing's syndrome. PMID- 7787996 TI - Adenolipoma of the thyroid gland. AB - A rare case of adenolipoma (thyrolipoma) of the thyroid gland is reported. Previously reported cases are reviewed and the pathogenesis of this unusual thyroid lesion is discussed. PMID- 7787998 TI - Coexistence of focal segmental glomerulosclerosis and diabetic glomerulopathy. PMID- 7787997 TI - Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium. AB - An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area. PMID- 7787999 TI - Physiological role of the insulin-like growth factor binding proteins. PMID- 7788000 TI - Acquired growth hormone resistance. PMID- 7788001 TI - Is repeated fine-needle aspiration cytology indicated in (benign) thyroid nodules? PMID- 7788003 TI - Serum levels of interleukin 6 and tumor necrosis factor-alpha in hyperthyroid patients before and after propylthiouracil treatment. AB - Contrary to the usual inhibitory role of tumor necrosis factor-alpha (TNF-alpha) in thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell-T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-alpha in patients with Graves' disease. To investigate this discrepancy we determined TNF-alpha and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-alpha levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-alpha, but not IL 6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen-antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-alpha and/or IL-6 elevation will be a predictor of disease recurrence. PMID- 7788002 TI - Decreased serum testosterone and free triiodothyronine levels in healthy middle aged men indicate an age effect at the pituitary level. AB - In an attempt to study further the age-specific influence on the hypothalamo pituitary-gonadal axis as well as the hypothalamo-pituitary-thyroid axis, we have now investigated young and middle-aged men, considering possible confounding factors. Both serum total testosterone, free testosterone and the total ratio of testosterone to sex-hormone binding globulin were significantly lower among middle-aged men as compared with young men (p = 0.02, p = 0.002 and p = 0.0003, respectively). In accordance with these findings there was also a decrease in the luteinizing hormone response to gonadotrophin-releasing hormone in the middle aged men (p = 0.02). Free testosterone was correlated significantly with the luteinizing hormone response (r = 0.32, p = 0.02). Serum free triiodothyronine was significantly higher among young men as compared with middle-aged men (p = 0.002) and the thyrotrophin-releasing hormone-stimulated thyrotrophin response was also higher in the young group compared with the middle-aged group. The present results may indicate that the age effect on serum levels of testosterone and free triiodothyronine is mediated at the pituitary level. PMID- 7788004 TI - Thyroid hormones in fibrocystic breast disease. AB - This study was undertaken to evaluate the role of thyroid hormones in fibrocystic breast disease. The concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and free triiodothyronine (T3) were determined in serum of 50 women with fibrocystic breast disease without macrocysts (cysts of over 3 mm diameter) and in the serum and breast cyst fluid (BCF) of 60 women with fibrocystic breast disease and macrocysts. Possible relationships between thyroid hormones and estradiol, dehydroepiandrosterone sulfate, testosterone, progesterone and 17-hydroxyprogesterone in the BCF also were analyzed. Serum thyroid hormone levels did not differ between the two groups. Free T3 levels were higher in BCF than in serum (p < 0.001), whereas T4, free T4 and TSH concentrations were lower in BCF as compared to serum (p < 0.001). Cysts were divided according to their K+/Na+ ratio because a ratio above 3 represents a predictor of malignant transformation. Free T3 concentrations were higher in BCF than in serum, in both low K+/Na+ cysts and in cysts with a K+/Na+ ratio above 3; those cysts with a high K+/Na+ ratio had the highest free T3 concentration. Free T3 in cysts correlated positively to the K+/Na+ ratio (r = 0.831; p < 0.001). Multiple linear regression analysis demonstrated that the concentration of free T3 in BCF was predicted statistically by the positive regression coefficient for the estradiol concentration. No candidate variable was included in the model to predict concentrations of TSH, free T4 or T4 in BCF. These data suggest an important role of free T3 in the physiology of fibrocystic breast disease. PMID- 7788005 TI - Fine-needle aspiration cytology of benign nodular thyroid disease. Value of re aspiration. AB - Fine-needle aspiration cytology (FNAC) has become a widespread procedure for the study of thyroid nodules (TN). Some authors recommend the practice of repeated punctures for their follow-up. This study was done to determine the usefulness of repeated FNAC in patients with benign nodular thyroid disease. We have studied 251 fine-needle re-aspirations performed on 116 females aged 45.6 +/- 14 years with benign nodular thyroid disease. The time elapsed between each consecutive FNAC was 1 year. No patients presented any changes in the size or consistency of their nodular goiters during this period; all FNACs were carried out by the same physician in the same thyroid area according to the Lowhagen technique, with a minimum of two or three aspirations of each nodule, and processed in the same way and valued by the same cytologist without any knowledge of previous cytological diagnoses. These were done using strictly classical criteria (Lowhagen). One hundred and five out of 116 patients (90.51%) with two consecutive FNACs (210) showed identical cytological diagnoses in the two specimens studied. The remaining 11 patients (9.48%) with two FNACs were diagnosed with colloid goiter and cyst alternately. Fifteen out of 19 patients (78.94%) with three FNACs showed identical cytological diagnoses in the three samples and the rest (21%) also demonstrated alternate diagnoses of colloid goiter and cyst. Our results show that the routine performance of repeated FNAC in the follow-up of females with benign nodular thyroid disease, without any clinical changes, is of limited usefulness. PMID- 7788006 TI - Urinary excretion rate of ceruloplasmin in non-insulin-dependent diabetic patients with different stages of nephropathy. AB - The level of ceruloplasmin, which is a more negatively charged protein than albumin, was measured by an immunoradiometric assay in timed overnight urine and serum samples from patients with non-insulin-dependent diabetes mellitus and healthy controls. None of the plasma proteins examined showed any cross reactivity in this assay. A linear correlation was seen between the ceruloplasmin level and the serial dilution of the sample. Western blot analysis using concentrated urine samples showed that the molecular weight of ceruloplasmin in the urine sample was the same as that of ceruloplasmin in the serum and standard samples. These findings indicated that the substance detected by this assay was truly ceruloplasmin. The urinary ceruloplasmin excretion rate (CER) and clearance of ceruloplasmin increased in parallel with the progression of albuminuria. The highest CER was found in macroalbuminuric patients, followed by micro- and normoalbuminuric patients and the healthy control subjects, the differences between the groups being significant. In view of the fact that the isoelectric point of ceruloplasmin (4.4) is more acidic than that of albumin, the present findings suggested that an enhanced CER was due either to the alteration of charge selectivity in the glomerular basement membrane with unaltered tubular function or to a defect of the non-discriminatory pores (shunt pathway) with unaltered tubular function. PMID- 7788007 TI - Cardiovascular effects of long-term L-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents. AB - Morphology and function of the left ventricle were evaluated by echo and Doppler examination in 16 females affected by Hashimoto's thyroiditis, aged 13.3 (4.5) years (range 7.9-24.6). They were on L-thyroxine (L-T4) treatment for a period of 2.8 (2.8) years (range 0.8-7.6) with a mean daily dose of 77 (18) micrograms/m2. Left ventricular mass, systolic and diastolic function, cardiac output and systemic vascular resistance did not differ from a control group matched for age, sex and body size. A further analysis of the patients according to thyrotrophin serum levels (less or more than 0.1 mU/l) gave similar results. Moreover, no relationship was found between echocardiographic findings and age, L-T4 daily doses, duration of treatment and serum level of thyroid hormones. We can therefore conclude that chronic L-T4 treatment for Hashimoto's thyroiditis at the given doses did not affect cardiac function and morphology in children and adolescents; however, a longer follow-up is needed before confirming the safety of this therapy in the long term. PMID- 7788008 TI - Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations. AB - Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated. PMID- 7788009 TI - Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group. AB - We evaluated the pituitary and gonadal suppression in 40 girls and nine boys treated with depot leuprorelin (3.75 mg sc if body weight > or = 20 kg, 1.87 mg if body weight < 20 kg) every 28 days for central precocious puberty. Gonadal suppression was obtained in most of the children with this dose: 3 months after initiation of the treatment, 85% of children had a peak plasma luteinizing hormone response to gonadotropin-releasing hormone < 3 IU/l and the gonadal axis remained suppressed throughout the duration of the study (up to 24 months). Four patients required higher doses of leuprorelin to achieve suppression. In two girls, a cutaneous reaction to the drug was associated with incomplete suppression and the treatment had to be interrupted. Plasma leuprorelin levels tended to increase from day 3 to day 28 after injection. Residual leuprorelin levels measured 28 days after injection were stable during the first year of the study. We conclude that an initial dose of depot leuprorelin of 3.75 mg sc every 28 days is efficient in most children with central precocious puberty. PMID- 7788010 TI - Effects of age and gender on pituitary-adrenocortical responsiveness in humans. AB - This study compared plasma concentrations of adrenocorticotropin (ACTH) and cortisol in young men (N = 10, mean age 24.4 years), young women (N = 10, mean age 25.4 years), old men (N = 8, mean age 81.6 years) and old women (N = 8, mean age 83.5 years) under basal resting conditions and after stimulation with either human corticotropin-releasing hormone (hCRH, 100 micrograms iv) or a combined injection of hCRH (100 micrograms) and arginine vasopressin (VP, 0.5 IU iv). Basal secretion of cortisol did not differ among groups, but basal concentrations of ACTH were diminished in young women (p < 0.01), indicating an enhanced adrenal sensitivity to ACTH in these subjects. Pituitary responses to hCRH did not differ between young men and women. However, responses to hCRH/VP were stronger in the young females (p < 0.01), suggesting an enhanced pituitary responsiveness to the augmenting effect of VP on ACTH release in this group. Pituitary-adrenal secretory responses were greater in old than in young men after sole injection of hCRH (p < 0.05) and even more so after combined injection of hCRH/VP (p < 0.01). In old women, pituitary-adrenal secretory responses were also greater than in young women (p < 0.05). But, in particular for responses to hCRH/VP, these effects were less distinct than within the men. Results indicate an enhancing effect of age on pituitary responsiveness to the hypothalamic secretagogues hCRH and VP, modulated by the subject's gender. PMID- 7788012 TI - Growth hormone response to growth hormone-releasing hormone (GHRH), insulin, clonidine and arginine after GHRH pretreatment in obese children: evidence of somatostatin increase? AB - To clarify the possible neuroendocrine mechanisms underlying the impairment in growth hormone (GH) secretion present in obesity, the GH response to GH-releasing hormone (GHRH, N = 6), insulin hypoglycemia (N = 6), clonidine (N = 7) and arginine (N = 8) after GHRH pretreatment (1 microgram/kg iv 2 h before the tests) was evaluated in 27 obese peripubertal children and in a group of normal-weight short-normal children (N = 26). Growth hormone-releasing hormone pretreatment and all further stimuli elicited a statistically significant GH response in both obese and short-normal children; in the latter group arginine did not induce a significant GH response. No differences were found among the GH responses after the second stimuli in obese children, while in short-normal children the arginine peak and area values were lower than after GHRH and clonidine. Comparison between the two groups showed similar baseline but higher stimulated GH levels in normal weight children after all tests except arginine, after which no difference was present. In conclusion, the neuroregulation of GH release seems to be similar qualitatively in normal-weight and obese youngsters; the different behavior observed after arginine, which is supposed to act through somatostatin inhibition, might be due to a chronic increase in somatostatinergic tone responsible for the lower stimulated GH levels in obesity. PMID- 7788011 TI - Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. AB - In recent years the health problems of adults with growth hormone deficiency (GHD) and the benefits of GH replacement therapy have received considerable attention. However, the reliability of conventional GH tests in the assessment of pituitary GH reserve in this group of patients is still controversial. In this study, we assessed GH secretion after the combined administration of GH-releasing hormone (GHRH) (1 microgram/kg iv) and GH-releasing peptide 6 (GHRP-6, 1 microgram/kg iv) in adult patients diagnosed with GHD by conventional GH testing, and correlate this response with insulin-like growth factor I levels. Twenty-one subjects (13 male, 8 female) with long-standing diagnosis of GHD aged 21-54 years were studied. In 13 subjects GH responses to GHRH plus GHRP-6 were markedly reduced (peak GH response < 10 mU/l), whereas in the remaining eight the response was greater (range 11-100 mU/l). In conclusion, our data show that combined administration of GHRH plus GHRP-6 elicited a significant increase in plasma GH levels in about 40% of patients diagnosed with GHD by conventional GH testing. PMID- 7788014 TI - Which iodolipids are involved in thyroid autoregulation: iodolactones or iodoaldehydes? PMID- 7788013 TI - Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. AB - The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophin-releasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice. PMID- 7788015 TI - delta-Iodolactones decrease epidermal growth factor-induced proliferation and inositol-1,4,5-trisphosphate generation in porcine thyroid follicles--a possible mechanism of growth inhibition by iodide. AB - delta-Iodolactone (6-iodo-8,11,14-eicosatrienoic delta-lactone, delta-IL), an iodinated derivative of arachidonic acid, has been shown to be synthesized in thyroid tissue and to inhibit thyroid cell proliferation. It is discussed as a potential mediator of the autoregulatory pathway of iodide in cyclic adenosine 3',5'-monophosphate (cAMP)- and thyrotropin (TSH)-independent growth. We therefore further localized the action of iodide and of delta-IL in isolated porcine thyroid follicles. Epidermal growth factor (EGF) and 12-O tetradecanoylphorbol-13-acetate (TPA) dose dependently stimulated thyroid cell proliferation, which could be inhibited by staurosporin (0.1-10 nmol/l). Iodide (2.5-40 mumol/l) as well as delta-IL (0.5-2 mumol/l) also dose dependently inhibited EGF- and TPA-induced proliferation. As the calcium ionophor A23187 (100 pmol/l) completely abolished the inhibitory effects of iodide and of delta-IL, this may indicate a mechanism of delta-IL at or proximal to the calcium-dependent activation of protein kinase C. The growth inhibitory effect was restricted to delta-iodolactones when delta-IL was compared to 6-iodo-8,11,14,17 eicosatetraenoic delta-lactone and 5-iodo-7,10,13,16,19-docosapentaenoic gamma lactone. It could not be prevented with propylthiouracil and therefore deiodination and a different iodide action is unlikely. Inositol-1,4,5 trisphosphate (IP3) and cAMP were measured in extracts from isolated porcine thyroid follicles stimulated with EGF (10 ng/ml) or TSH (1.0 U/l) revealing comparable kinetics in IP3 generation, while cAMP formation was only stimulated by TSH. delta-Iodolactone (2 mumol/l) only decreased EGF-induced IP3 formation, whereas TSH-induced IP3 and cAMP formation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788016 TI - Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin like growth factor II-like peptide. AB - A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l). Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 +/- 8.44 nmol/l, range 3.53 35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 +/- 3.75, range 31.99-50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l. Tumor tissue IGF II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14-3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08-1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II, thus excluding that peptide released by the tumor is a precursor molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788017 TI - Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I. AB - The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T4) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T4 and Triac, hypothyroid rats (N = 84) received over 6 days' injections of 10 nmol Triac or 2 nmol T4/100 g body wt per day. Biological effects of Triac and T4 were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 +/- 1.8 micrograms/l (hypothyroid 14.5 +/ 0.8 micrograms/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T4 injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in beta-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5'-deiodinase type I (5'D-I). The 6-day treatment with Triac had a markedly stronger effect on 5'D-I enzyme activity and mRNA levels than treatment with T4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788018 TI - Follicle-stimulating hormone-testosterone interaction in modulating steroidogenesis in bovine granulosa cells. I. Effect on progesterone production. AB - The aim of this study was to investigate the effects of testosterone on basal and follicle-stimulating hormone (FSH)-induced progesterone production by cultured bovine granulosa cells. Granulosa cells were isolated from small (< 5 mm) and large (> 8 mm) follicles and cultured for 48 h in 1 ml of Medium-199 with different concentrations of FSH (0.1, 1, 10 and 35 mg/l). In addition, the combined effects of different amounts of testosterone (1 nmol-10 mumol) and 1 mg/l FSH for 48 h on progesterone production by granulosa cells of both groups of follicles were studied; progesterone production during the subsequent 24-h incubation period was evaluated in the absence of hormones. In a third experiment, granulosa cells were treated with 500 micrograms of dibutyryl-cAMP and 10 mumol of testosterone for 48 h. At the end of each incubation period, the progesterone content in the culture media was determined by a validated radioimmunoassay. Basal progesterone release during the 48-h incubation period was higher in granulosa cells from small as compared to cells from large follicles; in both groups of cells, progesterone production was stimulated maximally by 1 mg/l FSH. The treatment with 10 mumol of testosterone induced a decrease of progesterone production in both groups of cells, while lower amounts exerted an inhibitory effect only in cells from large follicles. Furthermore, 10 mumol of testosterone inhibited FSH-induced progesterone release, while lower dosages were ineffective. Dibutyryl-cAMP stimulated significantly the progesterone output by granulosa cells of both groups and testosterone was effective in suppressing this increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788019 TI - Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring. AB - Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 250 micrograms/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788021 TI - Nurse heroes in Oklahoma City. PMID- 7788023 TI - Nursing gets a stamp of approval. PMID- 7788020 TI - Changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle. AB - The present study examined the changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle. Total cytoplasmic RNA was analyzed by Northern blot and slot-blot hybridization to examine the prolactin mRNA level. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine the Pit-1 mRNA level. Proestrous and estrous prolactin mRNA levels were significantly higher than the metestrous and diestrous levels, whereas Pit-1 mRNA levels of the estrous and metestrous stages were about two- to threefold higher than those of the proestrous and diestrous stages. Proestrous Pit-1 mRNA levels increased gradually from 10.00 h to 20.00 h, while prolactin mRNA levels slightly decreased until 14.00 h but increased later until 20.00 h. During the rat estrous cycle, especially in the afternoon of the proestrous day, changes of prolactin mRNA levels seem to follow a prior increase of Pit-1 mRNA. Therefore, Pit-1 may be partly involved in the regulation of prolactin gene expression according to the rat estrous cycle. Estradiol administration to ovariectomized rats significantly increased both the mRNA levels of prolactin and Pit-1, which suggests that the gene expression of Pit-1 is regulated by estrogen through indirect extracellular pathways. PMID- 7788022 TI - Walls of memories. PMID- 7788024 TI - Colors of the spectrum. Mental health care nursing in the home. PMID- 7788025 TI - Heroes on the homefront. PMID- 7788026 TI - Management perspectives. What common qualities are necessary for nurses to continue to successfully provide for patients and families in the future? PMID- 7788027 TI - Taking home health nursing into the 21st Century. PMID- 7788028 TI - Looking in a mirror: a nurse's experience with breast cancer. PMID- 7788029 TI - Olsten Kimberly QualityCare. PMID- 7788030 TI - Congenital coronary arterial anomalies of clinical relevance. PMID- 7788031 TI - Kawasaki disease. PMID- 7788032 TI - Arteritis associated with systemic disease. PMID- 7788033 TI - Small coronary artery disease in cardiomyopathy: hypertrophic cardiomyopathy resembling dilated cardiomyopathy. PMID- 7788034 TI - Coronary artery and peripheral vascular disease in cocaine users. PMID- 7788035 TI - Accelerated graft coronary artery disease in heart-transplant recipients. PMID- 7788037 TI - Modification of the circadian variation of symptom onset of acute myocardial infarction in diabetes mellitus. AB - BACKGROUND: The effects of diabetes mellitus and its treatment on the circadian variation of symptom onset in acute myocardial infarction were examined. METHODS: We obtained the time of symptom onset in 336 patients who had suffered acute myocardial infarction. RESULTS: As in earlier studies, the peak of symptom onset occurred in the late morning, between 6:01 a.m. and 12:00 noon. Although a similar circadian variation was observed in non-diabetic patients, the late morning peak was less prominent in diabetic patients. In diabetic patients receiving treatment, however, the circadian pattern was well preserved, whereas in untreated diabetic patients there were no peaks in the distribution of symptom onset of acute myocardial infarction. CONCLUSION: These findings suggest that autonomic disturbances in diabetes mellitus may blunt the late-morning peak in the frequency of onset of acute myocardial infarction. PMID- 7788036 TI - Association of lipoprotein levels with atherosclerotic changes in patients with coronary artery spasm and insignificant coronary artery stenosis. AB - BACKGROUND: Coronary artery spasm readily occurs at sites of atheromatous plaque. Some lipid profiles are related to the genesis of coronary artery spasm. In Korean patients, it is frequently observed in grossly normal coronary arteries, in contrast to the situation in western patients, who frequently have coronary artery spasm superimposed on significant coronary artery stenosis. Intravascular ultrasound examination has shown that mild or diffuse atherosclerotic changes in patients with focal vasospasm, even in the absence of angiographic coronary disease. OBJECTIVES: We studied prospectively 104 patients in order to find out which lipid profiles were associated with atherosclerotic changes in patients with coronary artery spasm. METHODS: Patients were grouped as follows: group I, control, 50 patients (34 men, 16 women); group II, 35 patients (26 men, 9 women) with significant coronary artery disease; group III, 19 patients (13 men, six women) with significant coronary artery spasm and either no coronary artery stenosis or insignificant stenosis. There was no significant difference in age (group I 55 +/- 1 years, group II 56 +/- 2 years, group III 54 +/- 2 years) or sex among the groups. The following parameters were evaluated: hypertension, cigarette smoking, diabetes mellitus, and lipid profile. RESULTS: The incidence of hypertension in group II patients was higher than in group I or III (P < 0.05). No significant difference was found in the percentage of cigarette smokers and patients with diabetes mellitus among three groups. The lipid profiles of each group were analysed. Group II patients had higher lipoprotein (a) levels (39 +/- 6 mg/dl) than those in group I (21 +/- 3 mg/dl) or group III (13 +/- 3 mg/dl) (P < 0.05). Other lipid profiles were not significantly different among the groups. CONCLUSION: Our results indicate that the atherosclerotic changes in the coronary arteries of group III patients were not associated with lipid profiles, including lipoprotein (a). PMID- 7788038 TI - Reduction of exercise-induced myocardial perfusion defects by isosorbide-5 nitrate: assessment using quantitative Tc-99m-MIBI-SPECT. AB - BACKGROUND: Although nitrates were introduced more than 100 years ago and have been used for the treatment of angina pectoris, there are still some open questions concerning the mechanism of their action on myocardial ischemia. There are also insufficient data regarding the influence of any anti-ischemic medication on the results of myocardial perfusion scintigraphy. METHODS: To assess the influence of a mononitrate, 30 patients with stable angina pectoris, coronary stenosis > or = 70% and normal left ventricular function were examined using quantitative Tc-99m-MIBI exercise-single photon emission computed tomography (SPECT). On the same day, 5 h after a randomized double-blind dose of 60 mg sustained-release isosorbide-5-nitrate or placebo, SPECT was repeated with identical stress protocol. The results were analyzed using a semi-automatic polar coordinate program that allows definition of areas with significant decreased blood flow expressed as a percentage of standard vessel area. RESULTS: In the vessel areas with the largest perfusion defects, the mean defect size decreased after isosorbide-5-nitrate from 38.2 +/- 31.0% to 29.1 +/- 33.8% (reduction by 24%; P < 0.05) and increased from 35.2 +/- 27.6% to 36.6 +/- 27.4% after placebo (increase by 4%; P = NS). The difference between defect size changes was also significant (P < 0.05). CONCLUSION: Acute administration of sustained-release isosorbide-5-nitrate significantly reduces the size of exercise-induced perfusion defects as assessed using quantitative Tc-99m-MIBI-SPECT. PMID- 7788039 TI - Long-term effect of gemfibrozil on coronary heart disease risk profile of patients with primary combined hyperlipidaemia. AB - BACKGROUND: The purpose of the present study was to assess the effect of gemfibrozil on 12 independent coronary heart disease risk factors in patients with primary combined hyperlipidaemia. METHODS: One hundred and five patients (62 men and 43 women), aged 53.2 +/- 4.8 years, were studied. The 10-year probability of myocardial infarction for the patients was calculated using the TYPMI (Ten Year Probability for Myocardial Infarction) computer program, which is constructed to co-evaluate 12 independent coronary artery disease risk factors. All patients followed a lipid-lowering diet and placebo for 3 months. At month 0, the patients received 1200 mg gemfibrozil daily, divided into two equal doses, for a period of 12 months. At months -3, 0, 1, 3, 6, and 12, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides [only if the low density lipoprotein (LDL) cholesterol to high-density lipoprotein cholesterol ratio was above 5], systolic blood pressure, plasma glucose, left ventricular mass index, and plasma fibrinogen were measured. Smoking habits, sex, age, physical activity and family history of coronary heart disease were also evaluated. The mean 10-year probability of myocardial infarction of all 105 patients at month 0 was 27.8%. This was significantly higher than the anticipated probability (10.4%, P < 0.001), resulting from an age- and sex-matched group of general population. RESULTS: During the third month of treatment, the following changes were recorded: total cholesterol -17%, LDL cholesterol -18%, very-low density lipoprotein (VLDL) cholesterol -45%, HDL cholesterol 20%, triglycerides 43%, apoprotein B -12%, apoprotein A-I 9% and plasma fibrinogen -21%. The estimated risk for myocardial infarction was reduced to 13.5% (delta m = -51%). All changes were significant and sustained until the twelfth treatment month. None of the patients were withdrawn from the study because of adverse effects of the treatment. CONCLUSION: Gemfibrozil reduces the estimated risk for myocardial infarction in patients with primary combined hyperlipidaemia at a level no different from the one of the general population. This beneficial effect of gemfibrozil, which was expressed by the third month and was evident for some time afterwards, was attributed to a significant reduction of triglyceride and fibrinogen levels, an increase of HDL cholesterol concentrations and a moderate decrease of total cholesterol and LDL cholesterol levels. PMID- 7788041 TI - Bibliography of the current world literature. PMID- 7788042 TI - Supreme court vs nurses--an unacceptable decision. PMID- 7788040 TI - Comparison of a low-molecular-weight heparin (nadroparin calcium) and unfractionated heparin as adjunct to coronary thrombolysis with alteplase and aspirin in dogs. AB - BACKGROUND: Low-molecular-weight heparins may have a higher benefit to risk ratio than unfractionated heparin in preventing perioperative thrombosis. The antithrombotic effects of low-molecular-weight heparins, given as adjunctive therapy to alteplase and aspirin, have not previously been compared with those of unfractionated heparin in experimental models of coronary artery thrombosis. METHODS: Occlusive coronary thrombosis was induced in 5 groups of 10 dogs by placing a copper coil into the left anterior descending coronary artery. After 1 h of occlusion, intravenous alteplase (0.1 mg/kg bolus followed by 0.01 mg/kg/min for 30 min), and aspirin (bolus of 5 mg/kg) were administered in combination with one of the following study treatments given intravenously for 2 h: placebo (group 1); unfractionated heparin (200 IU/kg bolus followed by 100 IU/kg/h, group II); the low-molecular weight heparin, nadroparin calcium, in three different doses (100 IU/kg bolus followed by 50 IU/kg/h, group III; 200 IU/kg bolus followed by 100 IU/kg/h, group IV; and 300 IU/kg followed by 150 IU/kg/h, group V). Coronary patency was assessed with angiography at 10 min intervals and hemostasis parameters were measured at baseline, after 1 h of occlusion, and 30 and 120 min after commencing drug administration. RESULTS: Optimal reperfusion [Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 without reocclusion] was more frequently observed in groups II (6/10), IV (8/10) and V (9/10) than in groups I (1/10) and III (3/10) (P < 0.05). Groups II and IV had similar patency rates (P = NS) and were therefore assumed to represent equivalent antithrombotic doses. Both nadroparin calcium and unfractionated heparin effectively prevented new thrombin generation as shown by repeated measurements of thrombin-antithrombin III complex levels in plasma. At equivalent antithrombotic doses, nadroparin calcium (group IV) was associated with significantly lower steady state values than standard heparin (group II) for activated partial thromboplastin time (41.3 +/- 48.9 versus 134.7 +/- 61.6 s), anti-Xa levels (2.4 +/- 0.5 vs 3.4 +/- 0.9 U/ml) and anti-IIa levels (0.8 +/- 0.1 versus 2.1 +/- 0.7 U/ml). CONCLUSION: Both nadroparin calcium and unfractionated heparin significantly enhance alteplase induced thrombolysis in aspirin-treated dogs. At equivalent antithrombotic doses, nadroparin calcium was associated with less prolongation of the activated partial thromboplastin time and lower steady-state anti-Xa and anti-IIa activities. PMID- 7788043 TI - No exit--what the Clinton healthcare plan will do for you. PMID- 7788044 TI - Top 10 myths about hospital restructuring and healthcare reform. PMID- 7788045 TI - Stuck somewhere between fight and flight. PMID- 7788046 TI - Oppressed group behavior: implications for nursing. PMID- 7788048 TI - Stearley's slant on nursing. Restructuring and the A.N.A. Who's side are they on? PMID- 7788047 TI - "When the going gets tough, the tough get going" --let's get going! PMID- 7788049 TI - Stearley's slant on nursing. Defensive nursing. PMID- 7788050 TI - Pulling from Peter to save Paul: is "floating" administratively or professionally sound? PMID- 7788051 TI - Handicaps to advantages--obstacles to opportunities. PMID- 7788052 TI - Sexual harassment in the workplace. PMID- 7788053 TI - Blowing the whistle on emergency department violence and aggression. PMID- 7788054 TI - A "capitol" idea for a trip. PMID- 7788055 TI - Nurse in the newsroom: visibility is key. PMID- 7788056 TI - Infectious disease exposure--a job hazard that can change a nurse's life forever! PMID- 7788057 TI - A voice in the dark. PMID- 7788059 TI - Employers, contracts, fees-for-service: but where are the nurses? PMID- 7788058 TI - Revolution follows the breast cancer epidemic. Macrobiotic mettle. PMID- 7788060 TI - The nurse paradigm. PMID- 7788061 TI - Self-care: the greatest challenge for nurses. PMID- 7788062 TI - Parliamentary select committees: democracy and the NHS. PMID- 7788063 TI - Multidrug-resistant tuberculosis. PMID- 7788064 TI - Sick and dying neurones: how to look at them and how to try and make them better. PMID- 7788065 TI - Neuroreceptor mapping with in-vivo imaging techniques: principles and applications. AB - Functional imaging techniques can now be used to map neuroreceptor distribution in the living human brain. This permits direct investigation of neurochemical abnormalities in neuropsychiatric disorders and opens possibilities for the development of more specific pharmacological treatments for these conditions. This article reviews the basic principles of neuroreceptor imaging and recent research findings in the area. PMID- 7788066 TI - Current therapies in motor neurone disease. AB - Motor neurone disease (MND) is a fatal neurological disorder, characterised by progressive weakness and wasting of muscles. The variety of hypotheses for its aetiopathogenesis are reflected in the large number of drugs tried in an attempt to modify disease progression. Although MND was first described by Charcot in the 1870s, there is as yet no known cure for the disease. PMID- 7788067 TI - The cervical spine in neurofibromatosis. PMID- 7788069 TI - Glomerular disease made easier: 2. PMID- 7788068 TI - Airway management in myasthenia gravis. PMID- 7788070 TI - Physiology of postoperative nausea and vomiting. AB - Postoperative nausea and vomiting remains a common cause of morbidity. This is a complex reflex involving multiple inputs via diverse receptor pathways which are integrated in the brainstem emetic centre. Factors related to the patient, the surgery, the anaesthetic and the recovery period are known to influence an individual's risk of vomiting. PMID- 7788071 TI - Decision-making in surgery: the surgical management of a raised serum calcium. AB - Successful surgical management of a raised serum calcium depends on an accurate preoperative diagnosis of hyperparathyroidism and an understanding of parathyroid pathology, combined with logical step-wise exploration of the neck. PMID- 7788072 TI - ECG clinic. 1. Atrial fibrillation 2. Onset ventricular tachycardia. PMID- 7788074 TI - Management of pulmonary Kaposi's sarcoma: new perspectives. AB - Pulmonary Kaposi's sarcoma is a frequent complication of human immunodeficiency virus infection. This article reviews the current approaches to the management of this difficult condition. PMID- 7788073 TI - Current issues in hypertension research and therapy. AB - Essential hypertension is one of the most common cardiovascular diseases and treatment is based on reducing overall cardiovascular risk. This article reviews current growth areas in hypertension research and practice. PMID- 7788075 TI - Community care. AB - On 1 April 1993 the community care legislation was implemented, heralding a new approach to the assessment of people's needs in the community. This article outlines how community care is working in practice and explores some of the key issues affecting clinicians. PMID- 7788076 TI - Infection with non-tuberculous mycobacteria. PMID- 7788077 TI - Stress in doctors: a personal view. PMID- 7788078 TI - Abdominal surgery in a patient with previous failed intubations. PMID- 7788079 TI - [The clinical utility of measuring the health-related quality of life]. PMID- 7788080 TI - [Measuring the health-related quality of life in pneumology: why and how]. PMID- 7788081 TI - [The Spanish translation and evaluation of a quality-of-life questionnaire in patients with chronic obstructive pulmonary disease]. AB - The Chronic Respiratory Disease Questionnaire (CRDQ), proposed by Guyatt et al, is a specific instrument used to assess quality of life in patients with chronic obstructive pulmonary disease (COPD). Our aim was to translate the questionnaire and validate it so that it could then be used as a measurement instrument in programs of respiratory rehabilitation. Sixty-five patients with COPD who were candidates for breathing therapy were enrolled in the study. Mean age was 64 +/- 7 years and all had severe air flow limitation, with FEV1 33 +/- 13% over reference values but not respiratory failure (pO2 70 +/- 10 mmHg). The questionnaire was subjected to a process of translation/back translation and disagreements over wording were discussed by a panel of bilingual speakers and the author himself. The validation process involved the following steps: 1) a comprehension study with a group of 5 patients, which revealed no special difficulties; 2) analysis of internal consistency or reliability by way of Crombach's alpha coefficient, which gave and overall score of 0.92 and area scores of 0.51 for dyspnea, 0.8 for fatigue, 0.86 for emotional factors and 0.84 for disease control, and 3) analysis of correlation between various lung function parameters and exercise test results (6 min of increasing effort and a stationary cycle), which showed weak but statistically significant correlations that were comparable to those found by the author of the original CRDQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788082 TI - [The quality of life in asthma: an evaluation of the AQLQ questionnaire for its use on a Spanish population. Asthma Quality of Life Questionnaire]. AB - The study of morbidity in asthma requires consideration not only of standard physiopathologic and function parameters, but also of the impact the disease has on the patient's life-style as he or she perceives it and evaluates it. The quantification of this factor, known as health-related quality of life (HRQL), is achieved by administering questionnaires specially designed for the purpose. We analyzed the reliability, content validity and construct validity (convergence and divergence) of one instrument, the Asthma Quality of Life Questionnaire (AQLQ) designed by Marks and colleagues. This questionnaire covers 4 dimensions (breathlessness, mood, social limitation and worrying) and gives a total score. After a process of translation and back translation the AQLQ was administered to 102 adult asthmatics living in an urban center, all of whom had been stable for at least the preceding 4 weeks. The following data were recorded: age, sex, duration of disease, FEV1, medication, dyspnea, hospital visits, nighttime symptoms and severity of disease (from the patient's own point of view and according to the scale of the International Consensus Report [ICR]). The reliability study (internal consistency with Crombach's alpha coefficient and inter-item correlation analysis) gave satisfactory results in all cases (range of r = 0.39 to 0.78; alpha = 0.78 to 0.91). Content validity (factorial analysis of the main components, oblique and orthogonal rotations) was less satisfactory, although 4 factors were found; these factors adjusted relatively well to one of the proposed sub-scales and together explained 65.2% of the total variance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788083 TI - [The quality-of-life questionnaire with asthma patients: the Spanish version of the Asthma Quality of Life Questionnaire]. AB - This paper describes the translation to Castilian and adaptation of a quality of life measurement instrument: the Asthma Quality of Life Questionnaire (AQLQ). The AQLQ, developed by Juniper et al, contains 32 items, 5 of which relate to habitual activities that the patient can choose from among a list of 26 possibilities. Answers are given on a scale of 7 points. To adapt this instrument for use in Spain, we subjected it to a process of translation/back translation by bilingual informants. The translated and original versions of each item, activity and answer option were evaluated as being totally equivalent (A), fairly equivalent but with some questionable wording (B), or of questionable equivalence (C). The naturalness and correctness of the Spanish version were also evaluated on a scale of 1 to 10. Three (9%) items and 1 (4%) activity were considered to be of questionable equivalence (C) and 12 (37%) items and 1 activity (4%) were considered to be of type B equivalence. The questionable aspects of types B and C equivalence were discussed in 2 meetings, along with expressions that were equivalent but unnatural or grammatically incorrect; the first meeting involved researchers and translators and the second was held with a group of 6 asthmatics. Consensus was finally obtained for each item and activity included in the second draft. That draft was then administered to another group of 7 patients in order to check comprehension and equivalence, after which a definitive version was produced by the researchers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788085 TI - [On how Galen corrected a diagnosis of pleurisy]. PMID- 7788084 TI - [The use of fibrinogen-thrombin via endoscope in the treatment of massive hemoptysis]. AB - We assessed the efficacy of fibrinogen-thrombin instillation through the fiberoptic bronchoscope to treat massive hemoptysis in patients to whom embolization of bronchial arteries was not available, was contraindicated or had failed. The fibrinogen-thrombin solution used was Tissucol, which in addition to 2% fibrinogen and 4 U/ml of thrombin, also contained factor XIII an aprotinin. The fibrinogen-thrombin solution was instilled with the aid of the Duplojec system and a 70 cm x 2 mm 4-way catheter. In 53 of the 628 fiberoptic bronchoscopies performed during the study, the indication was hemoptysis > or = 150 ml/12 h. Of these, bronchoscopic instillation of fibrinogen-thrombin was indicated in 5 cases because bronchial artery embolization was impossible. The point of bleeding was located by bronchoscopy in all cases and fibrinogen thrombin instillation controlled hemoptysis immediately and throughout the follow up period, which ranged 4 to 10 months. Morning expectoration of blood (< 10 ml) was observed in only 1 patient in the 3 days after treatment. The mean time taken for bronchoscopic exploration was 3 minutes (range, 2-7). In all cases fiberoptic bronchoscopy was performed without complications that might have required the procedure to be suspended. We conclude that the local use of fibrinogen-thrombin or fibrin glue instilled through the fiberoptic bronchoscope to the point of bleeding is a simple, fast and cheap way to control massive hemoptysis on a short and long-term basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788086 TI - [Interventional radiology in pneumology. State of the art]. PMID- 7788087 TI - [Primary Mycobacterium avium respiratory infection in nonimmunocompromised children]. AB - Mycobacterium avium is a common pathogen in barnyards, where it infects poultry and pigs. In human beings M. avium is most often found to cause disease in immunocompromised individuals, although it is also described fairly often as affecting patients with tuberculosis or chronic obstructive pulmonary disease; in recent years lung infections by M. avium have even been reported in elderly women with no underlying disease. Respiratory infection by this mycobacterium is unusual, however, in healthy children. We describe the case of a previously healthy 2-year-old boy with pneumonia whose course was complicated. After 6 months of treatment with various broad spectrum antibiotics there was no clinically or radiologically observable improvement. Other underlying diseases were ruled out, including infection by germs that cause atypical pneumonia. When all tests were negative, we investigated the possibility of primary infection by an atypical mycobacterium. A skin test was positive for M. avium. Acid-alcohol resistant bacilli were isolated from lung biopsy samples and the presence of tuberculoid granulomas were confirmed. Our patient then responded favorably after tuberculostatic treatment with 3 drugs (isoniazid, rifampicin and pyrazinamide). PMID- 7788089 TI - [Fulminant pneumonia caused by Streptococcus milleri: rare or not diagnosed?]. AB - Streptococcus milleri is increasingly isolated in laboratory samples and is worthy of consideration as a differential diagnosis in pyogenic infections, particularly in adults with underlying infections. We describe a well-documented case of pleuropulmonary infection in a young man with no known risk factors. We analyze the diversity of microbiological features of these bacteria in culture, as well as their clinical importance as pathogens. PMID- 7788090 TI - [A study of primary resistances to antitubercular drugs in Galicia]. PMID- 7788088 TI - [Pleuropericarditis as the only manifestation of Legionella pneumophila infection]. AB - Pleural effusion caused by Legionella is seen fairly frequently but is hardly ever of great clinical significance. Pericardial involvement has been described only rarely. We present a case of pleuropericarditis as the only sign of infection by Legionella pneumophila in a 66-years-old man with no prior history of disease. The patient came to the hospital with chest pain suggestive of pleurisy, low-grade fever, dry cough and dyspnea. The etiology was not suspected and the diagnosis was made retrospectively based on indirect immunofluorescence. After 3 weeks of treatment with high dose of erythromycin the patient recovered and remains asymptomatic to date. We conclude that infection by Legionella pneumophila should be suspected in patients with pleurisy or pericarditis of unknown cause. PMID- 7788092 TI - [The superior vena cava syndrome and juxtamediastinal bullae]. PMID- 7788091 TI - [Tartrazine-induced rhinitis?]. PMID- 7788093 TI - [Are inhaled steroids useful in pulmonary sarcoidosis?]. PMID- 7788094 TI - A global optimization method based on variable target functions for fitting of the experimental and calculated NOESY spectra. AB - A new method for structure refinement, based on optimization of the variable target function (Sugar and Xu, Prog. Biophys. Mol. Biol. 58, 61, 1992), is examined in order to explore the conditions of high-resolution polypeptide structure determination. The method of variable target function was used to analyze simulated NOESY spectra of different spectral resolutions, of different signal/noise ratios, and of different number of mixing times. The goodness of the results was assessed by comparing the known polypeptide conformation with the optimized ones, as well as by comparing the simulated experimental spectra with the spectra back-calculated from the optimized structures. According to the test calculations, in order to get high-resolution polypeptide structures, the number of constraints should be larger than the number of dihedral angles, and the constraints should be distributed over the dihedral angles more or less homogeneously. The success rate of the variable-target-function method in finding high-resolution structures was high until a critical signal/noise ratio, while below this threshold the success rate was low. The critical signal/noise ratio could be decreased, however, by increasing the number of mixing times. The test calculations show that the variable-target-function method is capable of high resolution polypeptide structure determination with a success rate of 85-90% under common experimental conditions, such as 10 constraints/residue, 40% noise/signal ratio, and six mixing times. PMID- 7788095 TI - Model-based maximum-likelihood estimation for phase- and frequency-encoded magnetic-resonance-imaging data. AB - A maximum-likelihood (ML)-based magnetic-resonance-imaging (MRI) reconstruction algorithm is established, based on frequency- and phase-encoded data. The model on which the ML method is based is a superposition of exponentially decaying, sinc-modulated sinusoids, arising from the basic Bloch equations for MR spectroscopy, modified to account for the distribution of resonance frequencies and phases used for spatial localization in the image field. Spatial-localizing gradients are assumed to be known linear functions of spatial coordinate position, with the x-encode (frequency) gradient applied continuously during the full duration of data collection, and the y-encode (phase) gradient applied during varying time periods before data collection. A single-voxel emitter becomes sinc-modulated in the x, y directions at rates proportional to voxel size and gradient strengths in the x-encode and y-encode directions. The full two dimensional MRI signal becomes a superposition of sinc-modulated, exponentially decaying, single-sinusoid emitters, one for each voxel. The ML estimation of spin density and spin-spin relaxation decay time images becomes a nonlinear least squares optimization problem; it is solved using an iterative expectation maximization algorithm for estimating multiple modulated sinusoids in noise. Phantom studies are presented, demonstrating the accuracy of the model and the application of the algorithm to spin-density and spin-spin relaxation decay time profiles. PMID- 7788096 TI - Breakthrough of single-quantum coherence and its elimination in double-quantum filtering. AB - Breakthrough of single-quantum coherence is shown to occur after application of a double-quantum filter with the conventional four-step phase-cycling scheme. This single-quantum breakthrough is due to the intersequence stimulated echo which has been generated by the radiofrequency pulses in the preceding pulse sequence and appears at the same time as the double-quantum coherence signal in the current pulse sequence. Moreover, the phase of the intersequence stimulated echo is the same as the phase of the double-quantum coherence signal; i.e., the phase of the intersequence stimulated echo is twice the phase change of the radiofrequency pulses in the creation period when their phase is rotated in accordance with the conventional four-step phase-cycling scheme. Consequently, the intersequence stimulated echo passes through the double-quantum filtration in the conventional four-step phase-cycling scheme and gradient pulses. A new phase-cycling scheme which can filter out the single-quantum breakthrough signal is proposed here and its effectiveness is verified experimentally and by computer simulations. PMID- 7788097 TI - Identification and quantitation of phenylalanine in the brain of patients with phenylketonuria by means of localized in vivo 1H magnetic-resonance spectroscopy. AB - Localized proton MR spectroscopy was used to identify phenylalanine (PHE) and to quantitate its cerebral concentration in patients with type I phenylketonuria (PKU). Data acquisition was optimized for the detection of low-concentration metabolites, using a short TE (20 ms) double Hahn-echo localization sequence for large volumes within the head coil and for smaller volumes using a surface coil. Previously described methods to quantitate localized MR spectra were extended to cover the case of low-concentration metabolites, unevenly distributed in three brain compartments and measured in difference spectra only. PHE content was determined in difference spectra of four PKU patients with respect to normals and in one patient before and after an oral load of L-PHE. PHE concentrations of 0.3 to 0.6 mmol/kg brain tissue were obtained, resulting in a concentration gradient for PHE between blood and brain tissue of 2.4 to 3.0. No significant changes were found for the abundant metabolites in gray or white matter. Previously reported MRI changes were confirmed to be due to increased cerebro-spinal-fluid-like spaces. PMID- 7788099 TI - Randomization approach to water suppression in multidimensional NMR using pulsed field gradients. PMID- 7788098 TI - Broadband SQUID NMR with room-temperature samples. AB - Superconducting quantum interference devices (SQUIDs) are the most sensitive detectors of magnetic fields. We have used an untuned broadband SQUID detector to detect transverse nuclear magnetic-resonance signals from samples of mineral oil, salt water, and animal tissue at room temperature. Proton NMR signals have been detected from about 20 to 450 kHz. We have also detected fluorine, sodium, and possibly phosphorus NMR signals. SQUID NMR shows promise in NMR imaging, since the SQUID's sensitivity and broad bandwidth make it ideal for low-field imaging. SQUID NMR may also be useful for low-field spectroscopy in biology, chemistry, and materials science. PMID- 7788100 TI - Band-selective heteronuclear cross polarization in liquids. PMID- 7788101 TI - Relative effects of protein-mediated and ligand-mediated spin-diffusion pathways on transferred NOESY, and implications on the accuracy of the bound ligand conformation. PMID- 7788102 TI - The impact of direct refinement against proton chemical shifts on protein structure determination by NMR. PMID- 7788103 TI - Neurontin--1 year on. London October 1994. PMID- 7788104 TI - Withdrawal of antiepileptic drugs (AEDs) in seizure-free patients, risk factors for relapse with special attention for the EEG. AB - When a patient has remained free from seizures for several years while taking antiepileptic drugs (AED) the question arises whether or not the medication can be withdrawn. Therefore it would be desirable to be able to identify reliably those patients who will remain seizure-free without treatment. Numerous variables might be of prognostic importance but our knowledge about the significance of demographic, genetic, aetiological, pathophysiological and treatment-related factors remains extremely poor. Although an abnormal inter-ictal EEG has been repeatedly cited as predictive of relapse during and after AED withdrawal, there is little evidence to support this view. There is a need for more precise individual prediction of risk but as long as patients with forms of epilepsy with widely varying prognosis are grouped together in AED withdrawal trials the outcome of these trials will never reach consensus about the relapse risk and about the possibility of predict relapse in individual patients. PMID- 7788106 TI - Vigabatrin in the management of generalized seizures in children. AB - The interpretation of the results of the use of vigabatrin (VGB) in generalized seizures and epilepsies in children has been difficult. Most studies have assessed patients on the basis of both seizure type and epilepsy syndrome and the numbers of patients have been small. Some 'generalized' epilepsy syndromes (specifically the Lennox-Gastaut syndrome) are characterized by multiple seizure types which are frequently not analysed individually in terms of drug response. By contrast West syndrome is easier to evaluate as the spasms are the only, and characteristic, seizure type. Vigabatrin has been used as both add-on, and monotherapy in the treatment of spasms. The results of add-on studies suggest that symptomatic spasms respond best, with 40-100% of children becoming spasm free and many others showing a reduction in seizures of over 50%. The limited, reported data on VGB-monotherapy in West syndrome have been encouraging with over 50% of patients experiencing a total and sustained control of seizures with minimal or no adverse events; however, the pattern of response (symptomatic cases responding better than cryptogenic cases), has not, as yet, been confirmed. The 'non-progressive' myoclonic epilepsies tend to be exacerbated with 25-50% of patients experiencing an increase in seizure frequency; this is an interesting observation in view of the improvement seen in infantile spasms, which are also classified as a myoclonic seizure. The use of VGB in other generalized seizures and epilepsy syndromes has been neither assessed, nor reported. This reflects the fact that these seizures/syndromes are easily and well controlled using the 'older' anti-epileptic drugs. PMID- 7788105 TI - Adjunctive therapy in epilepsy: a cost-effectiveness comparison of alternative treatment options. AB - A pharmaco-economic study of the administration of adjunctive therapy in patients with chronic epilepsy is described. A decision-analytic model has been used, which represents the consequences of treatment over a 1-year time period, when one of three drugs is used first. The cost-effectiveness ratio for clobazam, lamotrigine and vigabatrin have been calculated. The expected cost per patient of treatment over the 1-year period was up to 50% higher with vigabatrin and lamotrigine compared with clobazam, with a cost-effectiveness ratio around 40% higher. PMID- 7788107 TI - Changes of central benzodiazepine receptor density in the course of anticonvulsant treatment in temporal lobe epilepsy. AB - The first investigation of the central-type benzodiazepine (BZ) receptor density before and following 2 months successful treatment with carbamazepine (CBZ) in a patient with temporal lobe epilepsy (TLE) using 123I-labelled Iomazenil (a specific lipophile central BZ receptor compound) and single photon emission tomography (SPET) is reported. First, a focal slowing of the EEG in the left temporal area was noted and a corresponding reduction of the central BZ density of the left temporal lobe was found. After 2 months of treatment the patient was symptom-free, and a normal BZ receptor density and no pathological EEG signs were found. The increase in central BZ receptor binding sites might be related to the anticonvulsant effects of CBZ mediated by the so-called peripheral BZ receptor sites. PMID- 7788108 TI - New antiepileptic drugs--an explosion of activity. AB - The low therapeutic index of established antiepileptic drugs coupled with a better understanding of the pathophysiology of seizure production has led to the development of a range of new therapeutic agents for the treatment of epilepsy. In this review, the three drugs recently licensed in the UK (vigabatrin, lamotrigine and gabapentin) are profiled, together with several of the more promising up-and-coming compounds (oxcarbazepine, felbamate, tiagabine, stiripentol, remacemide and topiramate). Future avenues for clinical research in the pharmacological management of the epilepsies involve their rational use both singly and in combination. PMID- 7788109 TI - Epilepsy and associated effects on adaptive behaviour in adults with Down syndrome. AB - A total of 201 adults with Down syndrome were investigated, of whom 32 (15.9%) had epilepsy. A bimodal age distribution for seizure onset in childhood and later in middle-age was found. Good seizure control was associated with early onset epilepsy. Down syndrome adults with epilepsy scored significantly higher overall on the adaptive behaviour profile but did not have significantly greater maladaptive behaviours. PMID- 7788110 TI - Vigabatrin monotherapy in resistant neonatal seizures. AB - Seizures in a term infant with Ohtahara syndrome, associated with polymicrogyria, and a pre-term neonate with similar clinical features, failed to respond to conventional anticonvulsants, but were controlled with vigabatrin monotherapy. Another infant with Aicardi syndrome improved with vigabatrin. Autopsy in the first infant showed no evidence of intramyelinic oedema. The developmental outcome in the two survivors was better than expected for their condition. PMID- 7788113 TI - Epilepsy in people with learning disabilities. PMID- 7788111 TI - Seizures and 'disappearing' brain lesions. AB - BACKGROUND--Patients with seizures may have abnormal brain imaging. Lesions demonstrated on computerized tomography or magnetic resonance imaging often suggest the underlying cause of the seizures, and may prompt an invasive investigation for diagnosis and treatment. In an increasingly recognized subset of patients however, the imaged lesions spontaneously resolve. While poorly understood, these 'disappearing' lesions may in fact be the consequence of seizures, rather than the cause. Two patients with 'disappearing' lesions are presented: the first patient had a proven cause, the second a probable one. Case 1. A patient with new onset seizures had an abnormal MRI. An angiogram confirmed thrombosis of the straight sinus. On follow-up, she was doing well; repeat imaging was normal with resolution of the lesion. Case 2. A patient with a long seizure history had been well controlled on medications, and had no change in frequency of her seizures. She was found to have a left homonymous hemianopsia. MRI revealed a right parieto-occipital lesion. The patient refused further work up and was lost to follow-up. She returned almost a year later; repeat imaging was normal. CONCLUSION--Patients with seizures and abnormal imaging suggestive of structural lesions may occasionally have lesions that resolve spontaneously. While some diagnoses remain elusive, an important consideration to exclude in these patients is venous thrombosis. PMID- 7788112 TI - Rechallenge with lamotrigine after initial rash. AB - Eight patients rechallenged with lamotrigine after initial exposure which resulted in a skin rash are reported. On reintroduction of the lamotrigine, six of the patients had no recurrence of the rash. Of the other two patients, one had the occurrence of a mild fluctuating and qualitatively different skin rash on rechallenge. The other patient had developed a dose-related rash on initial challenge resulting in a dose reduction. The first attempt to re-increase the dose resulted in reappearance of the rash which again disappeared on dose reduction. However a further attempt to re-increase the dose did not result in reappearance of a rash. It is suggested that patients who experience a rash but good therapeutic response to lamotrigine might be considered for re-dosing. PMID- 7788114 TI - The revised classification of non-convulsive status epilepticus. PMID- 7788115 TI - Multiple personality disorder and false memory syndrome. PMID- 7788116 TI - Religious experience within mental illness. Opening the door on research. PMID- 7788117 TI - Thought disorder or communication disorder. Linguistic science provides a new approach. PMID- 7788118 TI - Use of drugs in child and adolescent psychiatry. AB - BACKGROUND: The prescription of psychotropic drugs for children is a sensitive and highly contentious subject which may explain the apparent lack of uniformity and consistency in clinical practice. METHOD: This review is based on Medline and manual search of the literature. RESULTS: More than 1000 relevant references were found, and information has been culled from all these. Fifty particularly relevant articles have been selected for the reference list. CONCLUSION: Recent years have seen considerable research in this field, and a clearer picture of the benefits and limitations of drug use in children is emerging. PMID- 7788119 TI - The future of adolescent psychiatry. AB - BACKGROUND: Appraisal of the future of adolescent psychiatry is required urgently, in view of the increasing scrutiny of mental health service priorities and the need for informed planning of psychiatric training and manpower requirements. METHOD: Future developments are set in the context of the changing concept and connotations of adolescence, the history and present position of adolescent psychiatry, and the rationale for separate services. RESULTS: Predictions are derived using trend extrapolation, in relation to a number of factors likely to determine the future. These include the social value attached to adolescence and youth, the status of adolescent medicine, the definition of clinical boundaries, the upper age-limit of services, investment in prevention, postgraduate training, research, the evaluation and marketing of adolescent psychiatry and, finally, its recognition as a separate sub-specialty. CONCLUSIONS: Predictions suggest that adolescent psychiatry will assume an expanding clinical role and increasing academic influence in the 21st century. PMID- 7788120 TI - Adolescent psychiatry services. AB - BACKGROUND: The way in which psychiatric services for adolescents in the UK are developing will be affected by recent changes in the organisation of the National Health Service. METHOD: The history of these services, and the different opportunities for development are reviewed. RESULTS: Ways in which high-quality clinical care can still be provided are indicated. CONCLUSION: Adolescent psychiatric services should be judged on their ability to provide such care, not merely on their ability to survive. PMID- 7788121 TI - Late-life depressive disorder in the community. I. The relationship between MMSE score and depression in subjects with and without psychiatric history. AB - BACKGROUND: In previous studies cognitive impairment in depressed elderly in patients tends to be associated with a late onset of depression. This study tests the hypothesis that cognitive impairment is associated with depression only in elderly individuals with no history of psychiatric illness. METHOD: We investigated an age-stratified sample of 4051 elderly people living in the community, aged between 65 and 84 (AMSTEL). The relationship between depression (GMS-AGECAT diagnosis) and scores on the Mini Mental State Examination was studied in subjects with and without a reported psychiatric history (CAMDEX questionnaire). RESULTS: Low MMSE scores (MMSE < or = 25) were only associated with depression in subjects with no psychiatric history (young/old: OR = 2.75, 95% CI = 1.83, 4.19; old/old: OR = 2.21, 95% CI = 1.61, 3.03). CONCLUSIONS: We concluded that the combination of cognitive impairment and first-episode depression in elderly individuals may indicate cerebral deterioration. Depression as such may not be associated with cognitive impairment. PMID- 7788123 TI - Prevalence of depression after stroke: the Perth Community Stroke Study. AB - BACKGROUND: The Perth Community Stroke Study (PCSS) was a population-based study of the incidence, cause, and outcome of acute stroke. METHOD: Subjects from the study were assessed initially, by examination and interview, and at four- and 12 month follow-ups to determine differences in prevalence of depression between the sexes and between patients with first-ever and recurrent strokes. RESULTS: The prevalence of depressive illness four months after stroke in 294 patients from the PCSS was 23% (18-28%), 15% (11-19%) major depression and 8% (5-11%) minor depression. There were no significant differences between the sexes or between patients with first-ever and recurrent strokes. With a non-hierarchic approach to diagnosis of those with depression, 26% of men and 39% of women had an associated anxiety disorder, mainly agoraphobia. Nine per cent of male and 13% of female patients interviewed had evidence of depression at the time of the stroke. Twelve months after stroke 56% of the men were still depressed (40% major and 16% minor), as were 30% of the women (12% major and 18% minor). CONCLUSION: The prevalence of depression after stroke was comparable with that reported from other studies, and considerably less than that reported from in-patient and rehabilitation units. PMID- 7788125 TI - Positive life change and recovery from depression and anxiety. A three-stage longitudinal study of primary care attenders. AB - BACKGROUND: The objective was to examine the relationship between positive life change (PLC) and recovery from depression and anxiety. Following Brown et al (1988, 1992), we hypothesised: (a) that an excess of PLC would be found in the 3 month period before recovery compared with base rates ('excess hypothesis') and (b) that fresh-start and anchoring subtypes of PLC would trigger recovery from depression and anxiety respectively ('specificity hypothesis'). METHOD: One hundred and seventy primary care patients with a depressive and/or anxiety disorder, selected from 1994 consecutive attenders, were assessed at baseline and at 1-year and 3.5-year follow-ups on life change (LEDS) and psychopathology (PSE and Course Interview). RESULTS: Our results appeared to confirm the excess hypothesis regarding depression and anxiety (twofold excess was found prior to recovery), but not regarding mixed anxiety/depression. They did not support the specificity hypothesis. CONCLUSIONS: PLC facilitates recovery but is neither a necessary nor sufficient condition for remission. Difficulty reduction is the most important recovery-enhancing factor. PMID- 7788122 TI - Late-life depressive disorder in the community. II. The relationship between psychiatric history, MMSE and family history. AB - BACKGROUND: In previous studies, dementia was linked to a family history of dementia and Down's syndrome. This study tested the hypothesis that late-life depression accompanied by cognitive impairment in elderly individuals with no history of psychiatric illness is also associated with these family histories. METHOD: We investigated an age-stratified sample of 4051 elderly people in the community aged 65-84 (AMSTEL). The relationship between family history (CAMDEX questionnaire) and depression (GMS-AGECAT diagnosis) was studied. RESULTS: A family history of mental health problems was associated with all subtypes of depression. Family history of dementia was associated with depression in subjects with a psychiatric history, but a family history of Down's syndrome was only associated with the combination of depression and cognitive impairment in subjects with no history of psychiatric illness. CONCLUSIONS: The heritability pattern confirms the concept of a dementia-related subtype of late-life depression. PMID- 7788124 TI - Anxiety disorders after stroke: results from the Perth Community Stroke Study. AB - BACKGROUND: The prevalence of anxiety disorders in 294 patients who survived to four months in the Perth Community Stroke Study (Perth, Australia), and a follow up of these patients at 12 months, are presented. METHOD: Diagnoses are described both in the usual DSM hierarchic format and by a non-hierarchic approach. Adoption of the hierarchic approach alone greatly underestimates the prevalence of anxiety disorders. RESULTS: Most cases were of agoraphobia, and the remainder were generalised anxiety disorder. The prevalence of anxiety disorders alone was 5% in men and 19% in women; in community controls, it was 5% in men and 8% in women. Adopting a non-hierarchic approach to diagnosis gave a prevalence of 12% in men and 28% in women. When those who showed evidence of anxiety disorder before stroke were subtracted, the latter prevalence was 9% in men and 20% in women. CONCLUSION: One-third of the men and half of the women with post-stroke anxiety disorders showed evidence of either depression or an anxiety disorder at the time of the stroke. At 12 month follow-up of 49 patients with agoraphobia by a non-hierarchic approach, 51% had recovered, and equal proportions of the remainder had died or still had agoraphobia. The only major difference in outcome between those with anxiety disorder alone and those with comorbid depression was the greater mortality in the latter. PMID- 7788126 TI - A comparison of community-based care for schizophrenia in south Verona and south Manchester. AB - BACKGROUND: The community-oriented mental illness services providing care to defined populations in south Verona, Italy (17,628 adults) and south Manchester, England (12,021 adults) have been compared to explore relationships between service organisation and patterns of service use. METHOD: The composition and function of the two services and the sociodemographic characteristics of the two centres are described and related to epidemiological data on service use in the community, out-patient clinic, day hospital and in-patient care. RESULTS: Treated incidence of all psychiatric diagnoses and of schizophrenia were significantly higher in south Manchester than south Verona, indicating that the referral filter between primary and secondary care is more permeable in Manchester. Patients known to the service were more likely to be admitted and to have shorter in patient stays in south Verona, indicating that the filter between in-patient care and the community is more permeable in Verona than Manchester. CONCLUSIONS: The organisation of services in Verona results in a smaller load on the mental health service; the shorter hospital stays can be related to better integration between hospital and community resources. The organisation of services in Manchester provides care for a greater proportion of the population, but would be likely to require increased resources for the mental health services over time. PMID- 7788127 TI - Cultural dimensions of psychiatric diagnosis. A comparison of DSM-III-R and illness explanatory models in south India. AB - BACKGROUND: Cross-cultural research to examine the cultural validity of diagnostic categories and underlying concepts requires methods that integrate epidemiological and anthropological frameworks. METHOD: The Explanatory Model Interview Catalogue (EMIC) and Structured Clinical Interview for DSM-III-R (SCID) were used to study 80 psychiatric out-patients with depressive neurosis at a clinic in south India. RESULTS: Summary kappa values of 0.75 for the EMIC and 0.68 for the SCID confirmed interrater reliability. Comparison of patient explanatory models and SCID diagnoses showed that patients emphasised somatic experience while clinicians emphasised depressive diagnoses. More than half the patients (55%) received a non-specific or dual diagnosis. CONCLUSIONS: These findings raise questions about the distinctiveness of depressive, anxiety, and somatoform (DAS) disorders for this population. PMID- 7788128 TI - Organised violence and the stress of exile. Predictors of mental health in a community cohort of Vietnamese refugees three years after resettlement. AB - BACKGROUND: The prevalence and course of mental disorders among Vietnamese refugees were studied, using a model including variables from different research traditions. METHOD: A consecutive community cohort of 145 Vietnamese boat refugees aged 15 and above were personally interviewed on their arrival in Norway and three years later. RESULTS: Three years later, there was, unexpectedly, no decline in self-rated psychological distress (SCL-90-R), almost one in four suffered from psychiatric disorder and the prevalence of depression was 17.7% (Present State Examination). Female gender, extreme traumatic stress in Vietnam, negative life events in Norway, lack of a close confidant and chronic family separation were identified as predictors of psychopathology. CONCLUSIONS: The effects of war and persecution were long-lasting, and compounded by adversity factors in exile. A uniform course of improvement in mental health after resettlement cannot be expected in all contexts. The affected refugees need systematic rehabilitation. PMID- 7788129 TI - The illusion of reality or the reality of illusion. Hallucinations and culture. AB - BACKGROUND: The aim of this review is to integrate research findings on the role of sociocultural factors in hallucinations and to relate these factors to current psychological theory and research. METHOD: The literature was surveyed by manual search, and the more reliable studies selected for the review. RESULTS: One hundred and thirteen publications were scrutinised and 30 of them were included in this review. CONCLUSIONS: Cross-cultural concepts of reality are related to the development and the threshold of hallucinations. Attitudes toward hallucinations tend to affect the emotional reaction to, and the degree of control of, these experiences. Awareness of these attitudes may help the diagnostician to distinguish between pathological and culturally sanctioned hallucinations. It is important that therapists consider the functional significance and meaning of hallucinations as well as the social context and the stimuli associated with them. PMID- 7788131 TI - Comparison of carbamazepine and lithium in the prophylaxis of bipolar disorders. A meta-analysis. AB - BACKGROUND: This meta-analysis assessed the equipotency of carbamazepine and lithium prophylaxis in bipolar disorder. METHOD: We selected only randomised, double-blind, controlled studies comparing carbamazepine with lithium from a manual and computerised search, and subjected them to a quality inventory. Their statistical results were weighted by their quality score and combined. RESULTS: Four studies met our criteria, yielding, overall, P = 0.15. This result is not straightforward because the studies showed significant heterogeneity (P < 0.01). CONCLUSION: Differences in statistical power and sensitivity of outcome measure explain this heterogeneity and the conflicting results of the studies. Therefore, the prophylactic efficacy of carbamazepine remains questionable. PMID- 7788130 TI - Effectiveness of zuclopenthixol compared with haloperidol in the treatment of behavioural disturbances in learning disabled patients. AB - BACKGROUND: We compared the efficacy of two neuroleptics with different receptor profiles (zuclopenthixol and haloperidol) in learning disabled patients with behavioural disturbance. METHOD: A double-blind crossover study (2 x 8 weeks; n = 34), interrupted by a two-week single-blind washout period, was employed. Assessments included the Schedule for Handicaps, Behaviour, and Skills (SHBS) and Clinical Global Impression (CGI). RESULTS: The SHBS score was significantly reduced for the zuclopenthixol cohort only. End-point analysis between the two drugs also showed an enhanced effect for zuclopenthixol over haloperidol. CGI scores did not reveal significant differences between the two drugs. CONCLUSION: Zuclopenthixol may be superior to haloperidol for the treatment of behavioural disturbances in mentally retarded subjects. PMID- 7788132 TI - Recurrent affective syndromes in bipolar and unipolar mood disorders at follow up. AB - BACKGROUND: It is in dispute whether affective relapse disrupts psychosocial functioning to the same extent in depressed and manic patients. METHOD: A prospective, naturalistic, longitudinal follow-up of 84 unipolar and bipolar affectively disordered in-patients was conducted to examine the extent of recurrent affective syndromes and their relationship to overall outcome. Global adjustment relative to relapse was assessed at 2- and 4.5-year follow-ups. RESULTS: Nearly half of the bipolar patients had subsequent syndromes, which were often associated with uniformly poor psychosocial functioning. Fewer than one quarter of those with recurrences had steady work performance. Bipolar patients taking lithium alone had fewer recurrences than those taking lithium as well as neuroleptics (P < 0.05). Bipolar and unipolar patients relapsed with equal frequency, but unipolar relapse was less often associated with readmission to hospital, work impairment, or uniformly poor functioning. CONCLUSION: Affective relapse in bipolar disorders was more detrimental to overall functioning than was recurrence in unipolar depression. PMID- 7788133 TI - Post-viral onset of anorexia nervosa. AB - BACKGROUND: The pathogenesis of anorexia nervosa (AN) is controversial. METHOD: A retrospective case series was studied to investigate the post-viral onset of AN. RESULTS: Four consecutive in-patients with severe restrictive AN spontaneously volunteered histories of 'glandular fever'-like illnesses immediately before the onset of their eating disorder. This association has not previously been described. Possible pathogenic pathways include both non-specific and specific viral disruptions in central homeostasis, particularly involving corticotrophin releasing hormone (CRH) regulation. CONCLUSION: Such mechanisms are speculative, but biologically and historically plausible. PMID- 7788134 TI - Neuropsychiatry and SPECT of an acute obsessive-compulsive syndrome patient. AB - BACKGROUND: A 71-year-old man with no previous psychiatric history presented with an acute onset of obsessive-compulsive disorder (OCD) symptoms associated with a right inferior parietal infarct. There were no abnormal neurological signs. There were no noteworthy abnormalities on neuropsychological testing. METHOD: Whereas a computerised tomography scan showed only a right inferior parietal infarct, a single photon emission computerised tomography (SPECT) scan revealed that in addition to the infarct there was decreased regional cerebral blood flow in the right basal ganglia and temporal areas. There was higher activity in the right orbitofrontal area than in the left. RESULTS: The patient improved with standard drug therapy and psychotherapy. CONCLUSIONS: SPECT is effective in the diagnosis of neuropsychiatric disorders such as OCD, and the pathological changes in brain metabolism detected by SPECT may be reversed by both drug therapy and psychotherapy. PMID- 7788135 TI - Characteristics of fire-setters. A study and proposed multiaxial psychiatric classification. AB - BACKGROUND: The study set out to review the relationship between mental disorder and fire-setting. METHOD: Sociodemographic, psychiatric, and medical data were retrospectively obtained from case notes of a group of 36 fire-setters referred to the North West Thames Forensic Psychiatry Service over a four-year period. RESULTS: Of the sample, 28% were female and one-third had no mental illness; 28% had a previous medical history of possible relevance. Psychoactive substance abuse was common. There was a significant disturbance of interpersonal relationships. Eighty-five per cent lived alone, and 44% of the female fire setters had a history of sexual abuse. CONCLUSION: On the basis of this study, a multiaxial classification system of fire-setting is proposed. PMID- 7788137 TI - ECT seizure duration and efficacy. PMID- 7788136 TI - Economics of treatment of depression. PMID- 7788138 TI - Toxic serotonin syndrome or extrapyramidal side-effects? PMID- 7788140 TI - Daniel Hack Tuke. 1895. PMID- 7788139 TI - Suicide prevention in Gotland. PMID- 7788141 TI - Diagnostic features of ankylosing spondylitis. PMID- 7788142 TI - They turned down my abstract again... PMID- 7788143 TI - Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint. AB - The value of serum cartilage oligomeric matrix protein (COMP) as a marker of disease progression was investigated in 81 hospital out-patients with clinical knee osteoarthritis (OA). Progressing patients were defined by a decrease of > or = 2 mm in joint space on X-ray or requiring knee surgery during the 5 yr of follow-up. Of the 57 patients for whom full data were available, 20 progressed and 37 did not progress. Serum COMP levels increased during the first year in those who progressed (mean 6.42 micrograms/ml) (S.D. 6.64) compared to those who did not progress [mean 0.07 microgram/ml (S.D. 4.99); P < 0.001]. Changes in COMP during the first year were related to baseline COMP (r = -0.672, P < 0.001) and weight-to-height ratio (r = 0.272, P = 0.47). After allowing for these variables, serum COMP increased during the first year in progressive patients by 5.04 micrograms/ml [95% confidence interval (CI): (2.61, 7.46)] more than in non progressive patients. Discriminant analysis gave a sensitivity of 70% and specificity of 78% at a cut-off value of 3.17 micrograms/ml. Baseline serum COMP levels did not differ between the groups but were related to late phase scintigraphy scan abnormalities. These observations suggest that the changes in serum COMP may have prognostic significance and are consistent with a model of OA in which early signs of episodic clinical progression can be found in the cartilage as well as in subchondral bone. PMID- 7788144 TI - Bcl-2 expression is unaltered in unfractionated peripheral blood mononuclear cells in patients with systemic lupus erythematosus. AB - It has been postulated that the high levels of autoantibodies observed in systemic lupus erythematosus (SLE) patients could result from abnormal longevity of polyclonally activated B-cells. This increased survival could be due to dysfunction of apoptosis, the normal regulatory process governing their life span. The protein product of the bcl-2 gene can enhance lymphoid cell survival by interfering with apoptosis. Moreover, transgenic mice overexpressing bcl-2 in their B-cells developed an autoimmune syndrome resembling SLE. To determine whether overexpression of bcl-2 occurs in SLE patients, bcl-2 protein was measured in peripheral blood mononuclear cells from 73 SLE patients, 20 healthy individuals and 47 patients with other autoimmune diseases. Only three lupus patients had raised levels of bcl-2 and there were no statistically significant differences in the mean bcl-2 levels measured in SLE patients compared to controls. Bcl-2 levels did not correlate with overall disease activity in SLE patients. PMID- 7788145 TI - Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor. AB - A number of investigators have reported that there are detectably elevated levels of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) in the synovial fluids of rheumatoid arthritis (RA) patients. However, the precise role of IL-6 and sIL 6R in the pathogenesis of RA remains unclear. In the present study we examined whether IL-6 and/or sIL-6R could induce the proliferation of synovial fibroblastic cells (SFC) obtained from a RA patient. Co-existence of IL-6 and sIL 6R induced SFC proliferation without needing any further stimulation. This proliferation was completely blocked by either anti-IL-6 or anti-sIL-6 antibody. In contrast, neither IL-6 nor sIL-6R alone induced SFC proliferation. Although sIL-6R alone could not induce SFC proliferation, it did however augment IL-1 beta induced SFC proliferation in a dose-dependent manner, but not tumour necrosis factor alpha-, platelet-derived growth factor-AB- or b-fibroblast growth factor induced proliferation. This augmentation was completely neutralized by the addition of anti-IL-6 or anti-sIL-6R antibodies. This may be explained by the fact that an amount of IL-6 sufficient to induce SFC proliferation in the presence of sIL-6R was found to be detectable in the IL-1 beta-stimulated-culture supernatant. This evidence suggests that IL-6 is very likely to be involved in synovial cell proliferation in the synovium of RA patients in co-operation with sIL-6R. PMID- 7788146 TI - Cytokine mRNA expression in the labial salivary gland tissues from patients with primary Sjogren's syndrome. AB - The pattern of cytokine mRNA expression in frozen minor salivary gland tissues from patients with primary Sjogren's syndrome (pSS) (n = 12) and controls (n = 8) using an in situ hybridization technique and oligonucleotide probes of interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha and beta (TNF-alpha and TNF-beta), interleukin-6 (IL-6), interleukin-2 (IL-2) and its receptor (IL 2R), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was examined. In addition to in situ hybridization, immunohistochemistry was used to identify the subset of cells expressing IL-2 and IL-4 mRNA. Mononuclear cells involved in the minor salivary gland lesions of pSS patients were found to express mRNA for pro-inflammatory cytokines such as TNF-alpha and IL-1 beta, and cytokines involved in the regulation of B- and T-cell function (IL-2 and IL-6). In contrast, only three biopsies from patients with pSS express mRNA of inhibitory cytokines such as IFN gamma and TGF-beta. Furthermore mRNA for IL-6 and IL-1 beta was also detected in the glandular epithelial cells suggesting that these cells may play a role in the pathogenesis of autoimmune lesion in Sjogren's syndrome. IL-10 mRNA was not detected while IL-4 mRNA was primarily detected in naive T-lymphocytes of patients with a mild and early lesion. These results suggest that local production of cytokines by both mononuclear and epithelial cells may be involved in the immune-mediated destruction of exocrine glands in patients with pSS. PMID- 7788147 TI - The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. AB - Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF alpha) have been implicated in the pathogenesis of rheumatoid arthritis (RA), and have therefore become therapeutic targets. An engineered human antibody, CDP571, that neutralizes human TNF alpha was administered intravenously in single doses of 0.1, 1.0 or 10 mg/kg to patients with active RA (n = 24). The effects of the antibody were compared in a double-blind fashion with those of placebo (n = 12). In an open continuation phase patients were given either 1.0 or 10 mg/kg. We found that CDP571 was well tolerated and caused reductions in markers of disease activity such as erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP): this was confirmed by a reduction in the disease activity score (DAS). There was a reduction in the number of tender joints, maximal in degree and duration after 10 mg/kg. Patients also documented a reduction of pain and relief of arthritis symptoms. The effects of 10 mg/kg CDP571 on ESR, CRP, tender joints, pain and symptom relief compared to placebo were statistically significant at weeks 1 or 2. The continuation phase, although open, confirmed both the safety and the beneficial effects of CDP571 in active RA. In conclusion CDP571, an engineered human anti-TNF alpha antibody, is well tolerated and, after a single dose of 10 mg/kg, provides improvements in symptoms, signs and serological markers of disease activity in patients with active RA. PMID- 7788148 TI - Human leucocyte antigen phenotypes and gold-induced remissions in patients with rheumatoid arthritis. AB - To assess possible associations between human leucocyte antigens (HLA) and the achievement of remission during gold treatment, HLA typing was performed in 67 rheumatoid arthritis (RA) patients with a gold-induced remission and in 25 control RA patients who discontinued gold therapy because of lack of efficacy. Both groups of RA patients showed a significantly higher frequency of DR4 antigen and lower frequency of DR6 than a control population. There were no significant differences in HLA antigens between remission-responders and non-responders. It is concluded that HLA typing is not helpful in predicting the therapeutic response to parenteral gold therapy. PMID- 7788150 TI - Antibodies to the 65 kDa mycobacterial stress protein in west Africans with rheumatoid arthritis, tuberculosis and malaria. AB - We have studied IgG antibodies to recombinant mycobacterial 65 kDa heat-shock protein in West African rheumatoid arthritis (RA) patients and local control groups, including those with tuberculosis or malaria. Mean levels were higher among the patients with RA than among healthy controls, but did not achieve statistical significance. Our findings may relate to the level of mycobacterial exposure in West Africa. PMID- 7788149 TI - Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. AB - The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended. PMID- 7788152 TI - Thyroid autoimmunity in systemic lupus erythematosus: the clinical significance of a fluctuating course. AB - A number of studies have demonstrated an association between thyroid autoimmune disease and systemic lupus erythematosus (SLE), but there is little information on the course of thyroid autoimmunity over time in SLE patients. We reviewed the thyroid serology of 150 SLE patients tested at or soon after diagnosis of SLE, and examined the follow-up data on those found to have positive thyroid serology. Thirty-one (21%) were thyroid autoantibody positive. Follow-up data were available on 20 of these patients, over an average of 7.9 yr. Twelve of the 20 patients (60%) were persistently thyroid autoantibody positive, but eight (40%) were thyroid autoantibody negative on at least one occasion during follow-up. All five cases of clinical thyroid disease that were diagnosed, and two out of three cases of subclinical elevation of thyroid-stimulating hormone (TSH), occurred in the group with persistently positive thyroid serology. We also retested the thyroid serology of 46 of the 119 patients who originally tested thyroid autoantibody negative, with an average of 6.2 yr between the two tests, and found that four (9%) now had positive thyroid serology. One had an elevated TSH. We conclude that thyroid serology follows a fluctuating course in a subgroup of SLE patients who are found to have positive thyroid serology on a single occasion. Although the number in this subgroup of our series was small, and the trend did not reach statistical significance, our findings suggested that this subgroup of patients is unlikely to develop clinical or subclinical thyroid disease. PMID- 7788151 TI - Muscle strength in healthy people and in patients suffering from recent-onset inflammatory arthritis. AB - Neuromuscular function was compared among 20 patients with relatively recent onset (symptomatic period 17 +/- 24 months) rheumatoid arthritis (RA) (experimental group; EG), and 20 age- and sex-matched healthy people (control group; CG). The comparison was repeated after a period of 6 months, when 16 patients had carried out progressive strength training. At baseline maximal grip strength and maximal dynamic unilateral strength of the knee extensors in the EG were significantly (P < 0.05) lower in comparison to the CG. The groups did not differ from each other in maximal isometric strength of the trunk flexors and extensors or the knee extensors. The 6-month dynamic strength training in the EG resulted in significant increases in maximal dynamic strength of the knee extensors (P < 0.001), in isometric grip strength (P < 0.001) and in isometric strength of the trunk flexors (P < 0.05) and extensors (P < 0.05) to the level of the healthy controls. Only minor changes took place in explosive strength and maximal isometric strength of the knee extensors. Erythrocyte sedimentation rate (P < 0.001), Ritchie's articular index (P < 0.01) and modified health assessment questionnaire (P < 0.01) improved significantly during the training period. The results suggest that inflammatory arthritis decreases dynamic and/or isometric muscle strength in selected muscle groups of the body already in the early stages of disease. However, progressive dynamic strength training rapidly increases the neuromuscular performance capacity of the patients even to the level of healthy people without detrimental effects on disease activity. PMID- 7788153 TI - Symptomatic enlarged iliopsoas bursae in the presence of a normal plain hip radiograph. AB - The clinical and radiological features of seven cases of enlarged iliopsoas bursae are presented, all of which had normal plain hip radiographs. Two cases had rheumatoid arthritis, one had septic arthritis diagnosed by synovial biopsy and the remaining four cases occurred as isolated findings, in the absence of any recognized hip pathology. A communication with the hip joint was demonstrated in one case associated with septic arthritis. All patients presented with symptoms of hip pain and limitation of movement. Two patients had a groin mass, one of which produced localized pressure symptoms and retroperitoneal extension. All patients had an arthrogram or bursogram performed. In the two cases where a mass was palpable, ultrasound and computed tomography were performed. We conclude that, in the presence of persistent hip pain or reduced range of movement, an enlarged iliopsoas bursa should be considered as a potential diagnosis, even in cases where the plain hip radiograph is normal. PMID- 7788154 TI - Inner ear involvement in mixed cryoglobulinaemia patients. AB - In order to evaluate the nature and prevalence of audiovestibular disturbances in mixed cryoglobulinaemia (MC), 32 consecutive MC patients were studied by a wide audiological and vestibular examination. Pure tone audiometry, impedance audiometry, brainstem response audiometry and vestibular function were performed. Patients with a previous history of ear damage due to other well-known agents were excluded from the study. In MC patients we found a rather frequent audiovestibular involvement (34.3%). Bilateral sensorineural hearing loss was found in seven MC patients (22%) and altered vestibular function test values in other seven subjects (22%). Moreover, anamnestic and clinical data revealed a high incidence of benign positional paroxysmal vertigo in our MC series. We can suppose that immune complex-mediated microvascular involvement of the labyrinthine vessels may be responsible for inner ear damage in MC. Thus, audiovestibular disturbances may be included among various organ involvement of the MC. PMID- 7788155 TI - Assessing clinical competence: recognition of case descriptions of rheumatic diseases by general practitioners. AB - The objective of this study was to detect strengths and weaknesses in the diagnosis of rheumatic diseases by general practitioners in order to set up post graduate training accordingly and to assess whether open-ended questions give results comparable with multiple choice-type questions. Fifty-one general practitioners were given eight written cases: rheumatoid arthritis (RA), ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), gout, polymyalgia rheumatica and pseudogout. Only signs and symptoms were provided. All cases were derived from real patients with a definite diagnosis. Each case was presented in both types of question formats. The cases were also presented to 23 rheumatologists. We found that in the open-ended question format 57.1% of the general practitioners gave the correct answers. Cases of RA, AS, gout and PsA were correctly diagnosed by > 70% of the general practitioners. Cases of polymyalgia rheumatica and reactive arthritis were correctly diagnosed by 55 and 39% of the general practitioners, respectively. The cases of pseudogout and SLE were correctly diagnosed by less than 11% of the general practitioners. Fifty-two per cent of the general practitioners gave the correct answers to the multiple choice-type questions. There was no statistical difference in the correct answers between the open-ended questions and the multiple choice-type questions. We concluded that assuming generalization of the results, training of general practitioners should include polymyalgia rheumatica, reactive arthritis, SLE and pseudogout. PMID- 7788156 TI - Role of prophylactic antibiotics in the prevention of late infection of prosthetic joints. Results of a questionnaire and review of the literature. AB - A postal survey has revealed wide variation in attitudes towards the need for prophylactic antibiotics in patients with implants who develop intercurrent infections, or who undergo surgical procedures. The available evidence is insufficient to reach any firm conclusions, however any patient who has an implant should receive swift treatment for intercurrent infections. PMID- 7788157 TI - Sulphasalazine-induced lupus in psoriatic arthritis. AB - Lupus syndromes have been described in rheumatoid arthritis and inflammatory bowel diseases treated with sulphasalazine. We describe two cases of lupus with clinical and serological disease, developing in seronegative, immunologically nude psoriatic arthritis following sulphasalazine treatment. On cessation of sulphasalazine the clinical and serologic features of lupus disappeared. This suggests that the lupus syndrome was induced by sulphasalazine rather than unmasked by it. PMID- 7788158 TI - Steroid myopathy induced by epidural triamcinolone injection. AB - Epidural steroid injections are widely used for the treatment of lumbago and sciatica although their efficacy has not yet been demonstrated in a convincing way. Moreover, systemic complications, although rare, have been documented. The present case report illustrates that even a single low-dose epidural injection may induce Cushing's syndrome and even steroid myopathy. PMID- 7788159 TI - Multiple joint avascular necrosis: beware of tuberculosis and human immunodeficiency virus--a rare but important cause. PMID- 7788160 TI - Lyme borreliosis presenting as a polymyalgia rheumatica-like syndrome. PMID- 7788161 TI - Musculoskeletal complaints in patients with hyperlipoproteinaemia. PMID- 7788162 TI - A further possible cause of diarrhoea caused by oral gold. PMID- 7788163 TI - Staphylococcal arthritis in human immunodeficiency virus infection. PMID- 7788166 TI - The place of acupuncture in medicine today. PMID- 7788165 TI - Evidence-based medical practice: the Cochrane Collaboration and osteoarthritis. PMID- 7788164 TI - Minocycline-related lupus. PMID- 7788167 TI - Frequency of autoantibodies to a major epitope on the carboxyl terminal fragment of CENP-B in patients with autoimmune disease. AB - The carboxyl-terminal fragment of CENP-B contains a major epitope for anti centromere antibodies (ACA). We have developed an enzyme-linked immunoassay (ELISA) for measuring antibodies to the 147-carboxyl-terminal amino acids of CENP B expressed as a beta-galactosidase fusion protein. The ELISA was 98% sensitive and 95% specific for detecting ACA in a population which included 46 patients with ACA detected by other means. Therefore, the CENP-B ELISA should prove a valuable tool in screening for ACA in populations at risk of developing systemic sclerosis, such as those with Raynaud's phenomenon. Levels of anti-CENP-B antibodies were not increased in unaffected relatives of probands with ACA. PMID- 7788168 TI - Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of patients with axial and peripheral form of ankylosing spondylitis. AB - IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in two separate patient populations of 99 and 85 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the presence or absence of peripheral arthritis. The patients with peripheral type AS had increased levels of IgM and IgA class antibodies against K. pneumoniae, whereas the patients with axial type AS had increased levels of IgG and IgA class antibodies to K. pneumoniae, as well as IgA class antibodies against E. coli and P. mirabilis bacteria. Sulphasalazine treatment decreased the IgM and IgA class antibodies in peripheral AS and IgA class antibodies in axial AS against K. pneumoniae LPS. The antibody levels were also decreased against E. coli and P. mirabilis bacteria in the sera of patients with axial AS. The immunological findings in patients with peripheral and axial form of AS were different from each other and thus may reflect different aetiopathogenetic mechanisms for these two types of AS. PMID- 7788169 TI - Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of ankylosing spondylitis patients with/without iritis and enthesitis. AB - IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in the sera of 98 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the clinical picture, i.e. presence or absence of iritis and enthesitis. The previous major finding of increased IgA class antibody levels against the whole K. pneumoniae bacteria in AS patients when compared to the healthy controls was not specifically associated with any single patient group in the present study. However, the patients with iritis had higher levels of IgA class antibodies to LPS of K. pneumoniae and E. coli when compared to the patients without iritis. In addition, the patients without enthesitis had higher level of IgG class antibodies against whole K. pneumoniae bacteria compared to the patients with enthesitis. The increased IgA class antibody levels against K. pneumoniae and E. coli LPS in AS patients with iritis may reflect an inflammatory process in the gut area. Furthermore, there were certain other differences in the immunological parameters between the AS patients with and without iritis or enthesitis and the possibility that they reflect different mechanisms involved in the disease processes cannot be excluded. PMID- 7788170 TI - Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients. AB - The pharmacokinetic profile of total and free methotrexate (MTX) and the effect of piroxicam on MTX pharmacokinetics was studied in 20 rheumatoid arthritis patients receiving a stable dosage of MTX (10 mg/week). Plasma protein binding ranged from 25 to 55%. To describe the variations with time of the unbound fractions a mathematical characterization relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The free fraction for a given patient can be evaluated from this relationship. Total clearance of MTX was not statistically different with piroxicam (8.0 l/h for total MTX, 13.7 l/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in tmax, area under the plasma concentration vs time curve, distribution and elimination half-lives, mean resonance time, and volumes of distribution. Although the highest observed total MTX concentration was significantly lower with piroxicam, there were no significant pharmacokinetic interactions between low-dose MTX and piroxicam. PMID- 7788171 TI - Adult onset Still's disease in northern India: comparison with juvenile onset Still's disease. AB - The present study compared the clinical and laboratory picture, the disease course and outcome in 31 patients having adult onset Still's disease (AOSD) with 23 patients having juvenile onset Still's disease (JOSD). The median age at disease onset was 20 and 7 yr for AOSD and JOSD patients, respectively. On analysing and comparing our data on these two groups, no significant differences emerged except that adults had a significantly lower time interval from disease onset to remission as compared to juveniles. Upon comparison of data on our AOSD patients with that published from abroad, rash, adenopathy and sore throat were less frequent. No clinical or laboratory variables were found to predict the subsequent disease course and outcome in either group. The functional outcome was good in about 70% of both groups and mortality was low. It is concluded that the clinical picture and outcome in AOSD is similar to that of JOSD. PMID- 7788172 TI - Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease. AB - Sulphasalazine is a commonly used second line agent in rheumatoid arthritis (RA) and other inflammatory joint diseases and is reported to be one of the least toxic of this group of drugs. Recently a severe allergic reaction and cases of lupus-like disease have been described in patients with RA after treatment with sulphasalazine. We describe five patients, all with inflammatory arthropathy who developed cutaneous vasculitis, lupus-like disease or atypical serology after exposure to sulphasalazine. Three of four cases investigated were found to have the slow acetylator phenotype. These reactions can complicate the diagnosis and delay discontinuation of the drug. Moreover, present guidelines for the diagnosis of drug-induced lupus do not apply to the majority of patients with sulphasalazine-induced lupus. PMID- 7788173 TI - Shoulder pain in a community-based rheumatology clinic. AB - The objective of this study was to assess the prevalence of different shoulder disorders likely to be experienced by a rheumatologist in a community-based rheumatology clinic. We assessed patients with shoulder pain presenting to a large general practice at a community-based rheumatology clinic. It was found that the more common conditions seen were rotator cuff lesions (65%), pericapsular soft tissue pain (11%), acromioclavicular joint pain (10%) and referred pain from cervical spine (5%). In conclusion this study has established the spectrum of shoulder disorders referred from general practice to a highly accessible community-based rheumatology clinic. The diagnostic processes to distinguish the different conditions rely chiefly on an accurate history and directed examination. PMID- 7788174 TI - The foot and ankle in rheumatoid arthritis. PMID- 7788175 TI - Intra-articular and soft tissue injections: a survey of current practice. AB - Intra-articular and soft tissue injections are the two most frequently used procedures in rheumatological practice. A questionnaire completed by 172 consultant rheumatologists aimed to ascertain the techniques used in these procedures. The results showed a wide divergence of practice in almost every aspect of technique. Respondents were willing to undertake injections in almost any location, but differed widely regarding personal and patient preparation before injection. About one-quarter used no local anaesthetic, the majority using local anaesthetic before or with the corticosteroid. Admission overnight or as a day case for injection of weight-bearing joints was practised by 18%. Post injection advice was extremely variable. The results suggest that there is at present no single consensus technique for intra-articular and soft tissue injections amongst British consultant rheumatologists. PMID- 7788176 TI - Inflammatory cytokine responses in juvenile chronic arthritis. AB - The inflammatory cytokines interleukin 1 beta (IL-1 beta) interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha) and the anti-inflammatory peptide--the interleukin 1 (IL-1) receptor antagonist--were measured in the plasma of children with juvenile chronic arthritis (JCA). In the two subgroups studied (polyarticular JCA and systemic JCA), there was good correlation between laboratory measures of disease activity C-reactive protein (CRP), erythrocyte sedimentation rate and clinical scores for disease activity. Despite higher levels of CRP in the systemic group IL-1 beta levels were lower and regression analysis recorded a difference in the relationship between CRP and IL-1 beta within the two clinical groups. In contrast, IL-6 levels were high in the systemic group and correlated with disease activity. No such correlation was observed in the polyarticular group. Five children with systemic JCA were studied during the febrile phase of their illness. IL-6 levels rose and fell with the fever. TNF alpha levels also rose and fell but out of phase with the fever. In contrast IL-1 beta levels were either undetectable throughout the febrile episode or only became detectable as the temperature reduced to normal. The IL-1 receptor antagonist was usually found in 1000-fold excess over IL-1 beta, levels rising and falling with the fever. These results demonstrate difference in the cytokine profiles and acute phase protein responses in polyarticular and systemic JCA. This would suggest different pathogenic mechanisms for these two groups of JCA with IL-6 being the more important cytokine in systemic JCA. PMID- 7788178 TI - Increase of activated factor VIIA and haemostatic molecular markers in juvenile chronic arthritis. AB - Activated factor VIIa (FVIIa), von Willebrand factor antigen (vWF:Ag), D-dimer and thrombin-antithrombin III complex (TAT) were measured to monitor coagulation status in patients with juvenile chronic arthritis (JCA). Subjects included 14 patients with systemic JCA, 16 with pauciarticular JCA and 16 with polyarticular JCA without disseminated intravascular coagulopathy, thrombosis or liver dysfunction. All types of JCA showed an increase of FVIIa, D-dimer and TAT, indicating enhanced activation of coagulation. In systemic JCA only there was also characteristically an elevation of vWF:Ag. We conclude that all types of JCA constitute a state of subclinical hypercoagulopathy caused by tissue damage and that additionally systemic JCA involves a prothrombotic state associated with or precipitated by vasculitis. PMID- 7788177 TI - Antinuclear antibodies in early onset pauciarticular juvenile chronic arthritis (JCA) are associated with HLA-DQB1*0603: a possible JCA-associated human leucocyte antigen haplotype. AB - A panel of 43 early onset pauciarticular (EOPA) juvenile chronic arthritis (JCA) patients have been typed for human leucocyte antigens (HLA) DRB1, DPB1, DQA1 alleles, and DQB1*0603 status using molecular-based methods. Increased frequencies of DRB1*08 [odds ratio (OR) 7.7, 95% confidence interval (CI) 2.6 22.3], DRB1*11 (OR 3.1, 95% CI 1.2-8.1), DRB1*1301 (OR 7.7, 95% CI 2.6-22.3), DPB1*0201 (OR 3.5, 95% CI 1.6-8.0), DQA1*0103 (OR 4.4, 95% CI 1.5-13.3), DQA1*0501 (OR 2.9, 95% CI 1.3-6.6), DQA1*0601 (OR 30, 95% CI 3.6-241) and DQB1*0603 (OR 7.3, 95% CI 3.0-17.6) were found in the EOPA-JCA group compared with Caucasoid controls. Stratification of the EOPA-JCA group into antinuclear antibody (ANA) positive (n = 18) and ANA negative (n = 25) individuals revealed that ANA positivity was only associated with DRB1*1301 (OR 4.2, 95% CI 1.0-17.3), DPB1*0201 (OR 4.0, 95% CI 1.0-15.7) and DQB1*0603 (OR 11.5, 95% CI 2.5-53.4). Further analysis of the relative contributions of HLA antigens to ANA status revealed that DQB1*0603 determined the primary HLA effect. No apparent interaction between DQB1*0603 and DRB1*1301 or between DQB1*0603 and DPB1*0201 was found to contribute to the association with ANA. We suggest that those ANA positive individuals with a restricted HLA background, (DQB1*0603 positive), defines a group of EOPA-JCA patients which will be especially valuable in the characterization of the ANA associated with EOPA-JCA. PMID- 7788180 TI - Chronic abdominal sepsis and migratory polyarthritis. PMID- 7788179 TI - The association between physical function and psychological problems in children with juvenile chronic arthritis. AB - Twenty-nine children with juvenile chronic arthritis, aged from 7 to 16 yr were studied using the Juvenile Arthritis Functional Assessment Report for Children and Parents questionnaires (JAFAR-C and JAFAR-P). The results showed that JAFAR-C and JAFAR-P were highly correlated (P < 0.001) with each other and also with a predicted JAFAR score (P < 0.05). The JAFAR score correlated with the arthritic joint count at the time of the study (P < 0.01), Steinbrocker classification (P < 0.001), pain score (P < 0.01) and stiffness score (P < 0.005). Evidence of psychological dysfunction was found in eight of the 29 children (27%). Six children (21%) scored 13 or more on the Rutter A(2) for parents and one patient scored more than nine on the Rutter B(2) for teachers. Only one child had a score on the Birleson self-rating scale that was high enough to suggest a likely diagnosis of depression. The median Lipsitt self-concept scale score was 86, that expected for a healthy population. There was no correlation between the psychological scores and any of the other functional measurements, although the numbers affected were small. There was no significant difference between type of arthritis at onset with regard to any of the scores obtained. PMID- 7788181 TI - Pamidronate and uveitis. PMID- 7788182 TI - Complementary therapies, the baby, and the bath water. PMID- 7788183 TI - Brachial plexitis in a patient with acute parvovirus B19 infection. PMID- 7788184 TI - Management of gout in patients with renal insufficiency and a gastrointestinal bleed--an answer to Dr Dunne's letter. PMID- 7788185 TI - Primary pyomyositis. Two more cases with atypical presentation in diabetic hosts. PMID- 7788188 TI - Is interferon alpha a therapy for hepatitis B-associated polyarteritis nodosa? PMID- 7788186 TI - Abducent and trochlear palsies in a patient with Sjogren's syndrome. PMID- 7788187 TI - Churg-Strauss syndrome with inflammatory orbital pseudotumour. PMID- 7788189 TI - Disseminated penicillinase-producing Neisseria gonorrhoeae in a patient infected with human immunodeficiency virus. PMID- 7788191 TI - Case reports of anesthesia complications. PMID- 7788190 TI - Tarsal tunnel syndrome in ankylosing spondylitis. PMID- 7788192 TI - The physiological effect of CO2 pneumoperitoneum in pediatric laparoscopy. AB - BACKGROUND: The physiological effect of CO2 pneumoperitoneum during laparoscopy is a great concern of the anesthesiologists. Its effect in pediatric laparoscopy has not been previously reported. The purpose of this study was to examine the physiological alteration of pediatric patients during CO2 pneumoperitoneum. METHODS: One hundred and twenty six children aged from 11 mon to 13 yr undergoing laparoscopic inguinal exploration were divided into three groups based on age orientation: group I comprising 40 children with age from 11 mon to 2 yr; group II 46 children with age between 2 to 5 yr; and group III 40 children aged from 5 to 13 yr. All patients received endotracheal anesthesia with halothane-N2O in 50% O2 and atracurium for muscle relaxation. Respiration was controlled by an Ohmeda 7000 ventilator with constant minute ventilation to maintain baseline end-tidal CO2 tension (PETCO2) between 32-33 mmHg. After anesthesia, CO2 was insufflated into the peritoneal cavity via the opened hernia sac. The intraabdominal pressure exerted by CO2 was 10 mmHg and the duration of pneumoperitoneum and laparoscopy was 15 min. We recorded airway pressure, PETCO2, body temperature, blood pressure, heart rate, heart rhythm, and oxygen saturation simultaneously at 1 min interval before, during, and after laparoscopy. RESULTS: The airway pressure and PETCO2 showed significant increases during laparoscopy (15-18% and 18-20% respectively) in all cases, but the percentage of increases were not significantly different among groups. However, the PETCO2 change in terms of time lag were different between groups: (1) the time lag from CO2 insufflation to the emergence of PETCO2 change (latent period) was respectively 0.7 +/- 0.1 (mean +/- SD) min in group I, 0.9 +/- 0.2 min in group II and 1.5 +/- 0.2 min in group III (p < 0.05); (2) the PETCO2 change from baseline to a plateau (ascending period) was respectively 4.2 +/- 0.6 min in group I, 6.3 +/- 1.0 min in group II and 9.1 +/- 1.1 min in group III (p < 0.05); (3) the PETCO2 decline from plateau to baseline after CO2 deflation (descending period) was respectively 6.2 +/- 0.5 min in group I, 8.3 +/- 0.8 min in group II and 12.0 +/- 1.3 min in group III (p < 0.05). The body temperature and hemodynamics including blood pressure, heart rate, heart rhythm, oxygen saturation were not significantly changed during laparoscopy in all groups. CONCLUSIONS: The changes of PETCO2 during laparoscopy did not influence the hemodynamic stability in our study. The younger children give a faster reaction time of PETCO2 change after CO2 insufflation than do the older children which may be related to the variation of physiological exhibition at different state of development. PMID- 7788193 TI - [The thermoregulatory threshold during surgery with propofol-nitrous oxide anaesthesia]. AB - BACKGROUND: Thermoregulatory responses are thought to be drastically suppressed by general anesthesia. In previous studies, it was shown that halothane, isoflurane and fentanyl-N2O combination decrease the threshold of vasoconstriction in general anesthesia. Propofol is a recently introduced intravenous anesthetic. The thermoregulatory threshold of its administration during surgery has not been quantified. MATERIALS: Fourteen unpremedicated ASA class I patients were anesthetized with N2O (67%) and propofol (2 mg/kg in bolus followed by 6 mg/kg/h infusion) during elective surgery of free flap. Patients were randomly assigned either to receive additional warming (n = 5) or standard (n = 9) management. Significant vasoconstriction was prospectively defined as the temperature gradient between forearm surface and finger-tip surface is > or = 4 degrees C, and the thermoregulatory threshold was defined as the esophageal temperature (core temperature) at a point where the skin temperature gradient between two tested zones exceeds 4 degrees C. RESULTS: Vasoconstriction did not occur in patients who received additional warming and they remained in nearly normothermia. The average minimum core temperature was 36.3 +/- 0.4 degrees C. In patients who underwent standard management the core temperature ranged from 32.8 to 34.6 degrees C (33.6 +/- 0.7 degrees C), signifying significant vasoconstriction. CONCLUSIONS: General anesthesia with propofol/N2O during surgery drastically inhibits thermoregulatory vasoconstriction. This effect should also be noted during long-term use of propofol (e.g. ICU-sedation). PMID- 7788194 TI - Use of a single lumen endotracheal tube and continuous CO2 insufflation in transthoracic endoscopic sympathectomy. AB - BACKGROUND: Transthoracic endoscopic sympathectomy (TES) is an accepted standard surgical treatment for palmar hyperhidrosis. For anesthetic management, a double lumen endobronchial tube is usually used to deflate the lung on the operative side. Recently we have applied continuous insufflation of carbon dioxide (CO2) into the pleural cavity to merely compress one lung while ventilating both lungs with a conventional single lumen endotracheal tube. METHODS: We have studied 45 patients (ASA I and II) who underwent bilateral TES, Thirty-three were ventilated by single lumen tube and the other 12 by double lumen endobronchial tube with one lung ventilation. In both groups I and II, CO2 was insufflated slowly through the scope to a intrapleural pressure of 20 cm H2O. Both lungs were ventilated with peak pressure of less than 20 cmH2O at tidal volume of 5-12 ml/kg at 10-16 beats/min. RESULTS: In these patients, no CO2 retention was noted. Oxygenation and cardiovascular stability were maintained and there were no complications. In the double lumen series, we found that oxygen saturation was less uniform and less stable than those in the single lumen series. CONCLUSIONS: It is concluded that the use of single lumen endotracheal tube with continuous insufflation of CO2 in TES is easy, simple and safe. PMID- 7788195 TI - Prior epidural injection of 10 ml normal saline reduces the incidence of inadvertant venous puncture in epidural catheterization. AB - BACKGROUND: Anesthetically, epidural neural blockade is widely used in the fields of surgery and obstetrics as well as in diagnosis and management of acute and chronic pain. However, inadvertent epidural venous puncture might be a serious problem, or even life-threatening particularly when drug is erronaneously injected and prompt diagnosis is not made correct and treatment is not instituted. Although many anesthesiologists suggested that injection of fluid into the epidural space before catheter insertion could prevent an epidural venous puncture, some others did not agree to it. This study aimed a assess the effect of injection of different volumes of saline into the epidural space before catheter insertion on the incidence of epidural venous puncture. METHODS: Three hundred ASA I or II patients receiving Extracorporeal Shock Wave Lithotripsy (ESWL) were randomly divided into three groups: group A (no saline), group B (5 ml of saline) and group C (10 ml of saline). After the injection of different volume of saline into the epidural space, an epidural catheter was inserted into the epidural space via a Touhy needle. The incidence of epidural venous puncture in each group was compared. RESULTS: The incidence of epidural venous puncture in group A and B was 14% and 11%, respectively. However, the incidence in group C (1%) was significantly lower than the other two groups. CONCLUSIONS: Our results suggest that injection of 10 ml saline into the epidural space before catheter insertion could significantly diminish the incidence of epidural venous puncture. PMID- 7788196 TI - [Clinical experience of laryngeal mask airway in lateral position during anesthesia]. AB - BACKGROUND: The laryngeal mask airway (LMA), inserted blindly into hypopharynx in patients in supine position, has been reported to be successful in the management of the airway and can provide adequate ventilation during anesthesia. In our study, we used LMA to maintain airway during anesthesia in patients in lateral position. METHODS: Eighty surgical patients, ASA class I-II, undergoing hemorrhoidectomy, were placed in lateral surgical position before induction. The induction agents were propofol (2 mg/kg), fentanyl (2 micrograms/kg) and atracurium (0.5 mg/kg, i.v.). When mouth opening can be done passively, a LMA was inserted into the mouth and advanced blindly over the tongue into the pharynx until resistance was felt. The rim was immediately inflated with air and several manual positive pressure ventilatory breaths were given to the patient to check for leaks in the LMA system. Chest movement was observed and bilateral lung ausculation was performed to confirm the adequacy of ventilation. Once the LMA was in place, enflurane with oxygen was administered until operation was completed. During the anesthetic course, EKG, blood pressure, pulse oximeter, end tidal CO2 and inspiratory pressure were monitored. RESULTS: Blind insertion of LMA in lateral position was successful in the first attempt in 70% (56/80) of patients. Twenty (18/80) patients required a second or third trial making the total successful rate of LMA insertion as high as 90% (74/80). In four patients, airway control through LMA was unsatisfactory due to large air leakage during manual ventilation. In two patients the LMA could not be inserted in proper position for maintaining airway. In six cases, the LMA was immediately removed and was substituted by face-mask for anesthesia. Two patients complained of postoperative sore throat. No other specific complications such as cough, laryngospasm and aspiration was noted. CONCLUSION: We demonstrated that LMA can be easily inserted and can provide effective patency of airway during anesthesia even in lateral position. It can be used as a substitute for face-mask in anesthesia in this position to prevent complications such as pressure injury that a face-mask may cause. PMID- 7788197 TI - Anesthesia for elective cardioversion: a comparison of thiopentone and propofol. AB - BACKGROUND: Cardioversion is still a trend of therapy for cardiac dysrhythmias. With the application of new intravenous anesthetics, cardioversion can be performed safely and effectively with rapid onset of and quicker recovery from anesthesia. We compared the anesthetic effects of a new synthetic agent, propofol, with thiopentone which was mostly used in the past. METHODS: Twenty four ASA class II to III adult patients scheduled for elective cardioversion in the coronary care unit were included in this study. All patients were given fentanyl (2 micrograms/kg, i.v.) three min before induction and were randomly assigned to receive either thiopentone 1.5 mg/kg (group 1) or propofol 1 mg/kg (group 2) for induction of anesthesia. Supplementary oxygenation was administered throughout. RESULTS: Both drugs could provide satisfactory anesthesia for elective cardioversion without major complications. Recovery time was shorter with propofol (p < 0.05). Comparing with previous reports, a higher incidence of apnea and prolonged sedation were noted in this study. This might be due to the additive effect of thiopentone or propofol with fentanyl. CONCLUSIONS: Both anesthetics were suitable for elective cardioversion with negligible side effects in hemodynamically stable patients. PMID- 7788198 TI - Foley catheter used as bronchial blocker for one lung ventilation in a patient with tracheostomy--a case report. AB - Anesthesia with one-lung ventilation is a good anesthetic technique for patients receiving thoracotomy in various underlying diseases. One lung ventilation can be achieved successfully by the application of a double-lumen endotracheal tube through the oral route. However, there are several situations such as low body weight, young age, difficult intubation, anatomic anomaly, and tamponading endobronchial bleeding in some adult patients, etc., in which lung separation by a double-lumen endotracheal tube may be relatively contraindicated because insertion is either difficult or dangerous. Bronchial blocker with a Fogarty embolectomy catheter has been used successfully for such situations. Here, we reported the clinical experience in using the Foley catheter as the bronchial blocker in a patient with tracheostomy. PMID- 7788200 TI - Tracheal stenosis following brief endotracheal tube intubation--a case report. PMID- 7788201 TI - [Complications of massive blood transfusion after intrathoracic hemorrhage--a case report]. AB - Acute hemorrhage leading to acute hypovolomic shock is a medical emergency carrying high mortality. It therefore requires prompt and effective treatment. We reported a case of lung tumor receiving lobectomy at our hospital. Repeated internal bleeding due to subclavian artery perforation occurred three times within three weeks after the surgery. During the period of resuscitation, the patient received emergently massive blood transfusion. Some complications of massive blood transfusion. Some complications of massive blood transfusion were noted later. A total of 89 units of whole blood, 34 units of fresh frozen plasma and 28 units of platelet was given. PMID- 7788202 TI - An urgent technique of applying high frequency jet ventilation in patients with extreme periglottic stenosis. AB - Applying high frequency jet ventilation (HFJV) to patients with extreme periglottic stenosis (EPS) carries high risk of barotrauma or severe circulatory depression, since the stenotic airway will result in inadequate outflow tract obstructing the passage of the expired gas. We encountered with emergent obstruction of the outflow tract in 13 patients with EPS during HFJV in endolaryngeal microsurgery (ELM) procedures. The phenomenon of progressive gas trapping occurred within seconds in all patients. Barotrauma and disastrous circulatory depression would occur if we had not recognized them and then taken some measures immediately. We surmounted these potentially lethal events without interrupting the surgical procedures and found neither hypoxia nor barotrauma in all these patients. This may attribute to an urgent technique, i.e., intermittent disconnecting the jet conduit at the junction of the proximal end of the insufflation catheter and the distal end of the patient connecting tube of jet ventilator during HFJV. PMID- 7788203 TI - Fat embolism syndrome following bilateral total knee replacement with total condylar prosthesis--a case report. PMID- 7788204 TI - Inhaled fenoterol pretreatment attenuates airway resistance response to endotracheal intubation. AB - BACKGROUND: Endotracheal intubation may induce vagal mediated bronchoconstriction. As fenoterol possesses bronchodilation effects, we studied the efficacy of fenoterol pretreatment on the increased resistance of total respiratory system (Rrs) caused by reflex bronchoconstriction in endotracheal intubation. METHODS: Fifty patients were randomly allocated into two groups; group A (n = 25) with fenoterol inhaled and group B (n = 25) with placebo inhaled 10 min before induction. Patients were induced with sodium thiopental and vecuronium and resistance was measured 2 and 5 min after intubation with a Bicore pulmonary function monitor. Suctioning of the airway was performed 1 min before each measurement. Patients were further categorized into four conditions by smoking history and the presence of sputum in the suctionings. Condition I included patients that were smokers with no sputum collected. Condition II had non-smokers with no sputum collected. Condition III had patients with sputum collected but with no smoking history and condition IV were patients who had sputum collected and had a smoking history. RESULTS: Patient who received fenoterol have significant lower total respiratory after intubation than those receiving placebo. There were no significant differences in post-intubation Rrs between smokers and non-smokers. Patients with sputum had the highest resistance after intubation with the placebo group. Heart rate and blood pressure were augmented in both groups. CONCLUSIONS: Fenoterol pretreatment produced lower post intubation Rrs after intubation when compared with the placebo group suggesting of a protective effect in vagal mediated bronchoconstriction. PMID- 7788199 TI - [Arytenoid subluxation following endotracheal intubation--a case report]. AB - A previously healthy 39-yr-old man was scheduled for exploratory laparotomy due to acute abdomen. There was no sign of difficult intubation. After induction of anesthesia with thiopental and succinylcholine, the trachea was easily intubated with a 7.0 mm cuffed endotracheal tube. Surgery for a ruptured appendix with 2 drainage tubes lasted for 75 min was uneventful. At the end of surgery, the endotracheal tube was removed without difficulty. On the 1st postoperative day, the patient developed stridor. The symptom persisted even after conservative treatment and removal of NG tube. On the 12th postoperative day, a telescopic videolarygoscopy revealed immobile right vocal cord with anterior and medial displacement to the right. Arytenoid cartilage was moderately edematous. A diagnosis of right arytenoid subluxation was then made. On the 17th postoperative day, a closed reduction of right arytenoid cartilage using direct laryngoscope was performed successively under general anesthesia. Eight weeks after the reduction, his voice and laryngoscopic findings were normal. There has been only 18 reports with 27 cases of this complication found in the literature. However, it is generally believed that it is not so unusual. The post-intubation syndromes, such as sore throat, dysphonia, odynophagia, difficulty in swallowing or breathing which persists beyond 5 days warrant ENT consultation. Abnormal mobility of vocal cord, edema over arytenoid area found by indirect laryngoscopy should suggest the complication. Further confirmation is then needed. Although the result of our case is good, the reduction should ideally be done within 24-48 h after the incidence to avoid unfavorable long-term sequelae. PMID- 7788205 TI - [The history and present status of biotechnology in the Czech Republic]. AB - The paper outlines the historical milestones in the development of biotechnology in the Czech Republic in the fields of research, education and manufacture. The section dealing with the present state describes fundamental research carried out in the institutes of the Academy of Sciences of the Czech Republic and the universities and technical colleges, the institutes of applied research subsidized by the pertinent ministries as well as privatized institutes. The numbers of institutes and researchers before and after the political changes in 1989 are compared and the grant agencies for support of science and research are listed. The section dealing with biotechnological industry characterizes the firms manufacturing the products and devices for pharmacy, agriculture, food industry and ecology. PMID- 7788206 TI - [Pharmaceutical services in theory and practice in the Czech Republic]. PMID- 7788208 TI - Bungee running: a further report. AB - Further to the report from Queen Mary's NHS Trust on bungee running affecting children, we present three cases of injury in adults. Two cases of injury presented to Noble's (Isle of Man) Hospital and one to Whiston Hospital, Merseyside. In all three cases, the competitors were trying to stretch the 'bungee' to grasp a pint of beer as a prize, much enthusiasm being shown by spectators. All injuries occurred when the competitors were catapulted backwards with some force. PMID- 7788207 TI - Surgical stabilization of spondylolisthesis in a wrestler. AB - Sporting activity in wrestlers operated on for spondylolisthesis is not well documented in the literature. We present the case of a wrestler with a grade I L5 S1 spondylolisthesis who was L4-S1 arthrodesed due to pain not relieved by conservative methods. One year after surgery he had returned to full wrestling activity, including competitions. Two years later, he continues to wrestle at the same level of competition. PMID- 7788209 TI - Physical and physiological profiles of Malaysian dragon boat rowers. AB - Maximal oxygen consumption (VO2max) and maximal workload attained (WLmax) were determined in 28 Malaysian dragon boat rowers who were exercised to exhaustion on an arm ergometer. Mean VO2max was 2.75 l min-1 at a mean WLmax of 195.5 W. Anaerobic endurance power of the arms, determined by cranking at 100 RPM at a workload of 400 W and the time taken to maintain the cadence until it fell to 75 RPM, was 34.9(+/- 2.3) s. Leg performance, as determined by standing long jump and vertical jump, was 140.0(+/- 4.5) kg m and 100.3(+/- 3.1) kg m s-1 respectively. Right hand grip strength was significantly (p < 0.001) greater than the left hand. Percentage body fat of the rowers was 11.8(+/- 0.6)%. These values represent the first measurements of their kind performed on dragon boat rowers in Malaysia. PMID- 7788210 TI - Do the competition rules of synchronized swimming encourage undesirable levels of hypoxia? AB - Recent anecdotal reports that some synchronized swimmers have become dizzy or disorientated towards the end of their performance, and in the worst cases fainted underwater, have caused concern. However, the rules of synchronized swimming encourage slow performance of compulsory figures, and an analysis of the competition placings and duration of underwater sequences showed that the highest rankings were gained by slowly performed compulsory figures and free programmes containing a long underwater sequence. The combination of breath-holding and the vigorous exercise involved suggests that some of the symptoms complained of by the swimmers might be due to hypoxia. We therefore studied the alveolar gas tensions in nine members of the Great Britain National Squad immediately following the performance of set figures and the initial underwater sequence of their free routine in a swimming-bath. All were cyanosed after the underwater sequences of the free routine and reported being mildly confused. The mean(s.d.) alveolar PO2 at this stage was 5.07(1.1) KPa, while three girls had an alveolar PO2 below 4 KPa, the lowest being 3.67 KPa. These gas tensions suggest that potentially dangerous levels of hypoxia may develop during competitive synchronized swimming and that prolonged underwent sequences should not be encouraged. PMID- 7788212 TI - Monitoring altitude acclimatization--a case study of an elite woman athlete. AB - A simple study monitoring altitude acclimatization, which is not intrusive to the athlete's training, is described. Particular attention is drawn to the change in production of lactate in response to steady state exercise, before and after altitude. The results suggest that a more thorough assessment of aerobic ability at altitude is required than that described in the British Association of Sports and Exercise Science (BASES) guidelines. It is also relevant to note that elevations in haemoglobin, promoted by altitude, can mask iron abnormalities. It is therefore recommended to assay for iron in addition to haemoglobin. PMID- 7788211 TI - Prediction of endurance running performance for middle-aged and older runners. AB - The purpose of this study was to develop regression equations that would sufficiently predict the endurance running performance (ERP) of middle-aged and older runners (n = 55, 43-79 years). Among many independent variables which were selected as possible predictors of the ERP, oxygen uptake corresponding to the lactate threshold (VO2@LT), or age was found to be the single best predictor. Some variables representing training habits correlated significantly but only moderately with the ERP. Linear multiple regression equations developed in this study were: V5km = 4.203 + 0.054X1 - 0.028X2 (r = 0.87) V5km = 4.436 + 0.045X1 - 0.033X2 + 0.005X3 (r = 0.89) V10km = 4.252 + 0.042X1 - 0.026X2 (r = 0.79) V10km = 4.371 + 0.037X1 - 0.031X2 + 0.005X3 (r = 0.82) VM = 3.207 + 0.048X1 - 0.022X2 (r = 0.91) VM = 3.707 + 0.038X1 - 0.031X2 + 0.005X3 (r = 0.93) where V5km, V10km and VM are the mean running velocity at 5 km, 10 km and marathon races, respectively, and X1 = VO2@LT (ml kg-1 min-1), X2 = age (year), and X3 = average running duration per workout (min). We suggest that the ERP of middle-aged and older runners can be predicted from a linear combination of VO2@LT and age or a combination of these variables plus average running duration per workout. PMID- 7788214 TI - At last? PMID- 7788213 TI - Amino acid metabolism in tennis and its possible influence on the neuroendocrine system. AB - To investigate amino acid metabolism during endurance exercise as well as its influence on plasma prolactin (PRL) we subjected eight nationally ranked tennis players (mean(s.d.) age 25.6(2.8) years, mean(s.d.) weight 83.9(5.7) kg, mean(s.d.) height 184.4(4.6) cm) to 4h of continuous tournament tennis. Venous and capillary blood samples were taken before and after the exercise. Amino acids were measured by HPLC-fluorescence detection as o-phthalaldehyde derivatives; nonesterified fatty acids (NEFA), ammonia, total protein, glucose insulin and PRL by enzymatic methods. Exercise caused a decline of branched-chain amino acids (BCAA) by 28(14)%. Elevation of NEFA resulted in a significant mean(s.d.) increase of free tryptophan (TRP) (9.7(2.6) [pmol/microliter] vs 17.8(6.4) [pmol/microliter]. The mean(s.d.) ratio of free TRP:BCAA increased by 165%(90) which favours entry of free TRP into the brain. However, PRL did not change significantly. We conclude that during long-lasting interval sports BCAA contribute as energy substrates. Alterations in competition of amino acids at the blood-brain barrier favour entry of free TRP into the brain. PRL changes cannot be explained by the increase in plasma level of free TRP or the ratio of free TRP:BCAA. PMID- 7788215 TI - Pain and pain tolerance in professional ballet dancers. AB - Pain experience in sport had been the subject of increasing research in recent years. While sports professionals have generally been found to have higher pain thresholds than control subjects the reasons for this are not entirely clear. The present study seeks to investigate one possible explanatory factor, the importance of the popular image of the physical activity and of the self-image of its participants, by examining pain experience in professional ballet dancers. Like sports professionals, dancers were found to have higher pain and pain tolerance thresholds than age matched controls in the Cold Pressor Test. However, they also reported a more acute experience of the sensory aspects of the pain. Explanations of this apparent paradox are discussed both in terms of the neuroticism scores of the two groups and in terms of the dancers' greater experience of pain and its relationship with physical activity. The results illustrated the importance of using multidimensional measures of pain in this type of investigation. PMID- 7788216 TI - Personal health benefits of Masters athletics competition. AB - Questionnaires (750 respondents, 44.4% response rate) examined the long-term health value of endurance exercise training in older age-classed competitors ('Masters Athletes', 551 men and 199 women) over a 7-year period (1985-1992). The majority had initially completed maximal exercise tests. The weekly time devoted to training, competition and exercise-related travel was 10 to 30 h, and the annual expenditure on clothing, equipment and entrance fees was typically in the range Canadian $500-1500. Despite their age (mean(s.d.) 58(10), current range 40 81 years), only 1.4% reported sustaining a non-fatal heart attack and 0.6% had required bypass surgery over the 7-year interval. The majority (90%) were very interested in good health; 76% considered themselves as less vulnerable to viral illnesses than their peers, and 68% regarded their quality of life as much better than that of their sedentary friends. The majority of former smokers had stopped smoking before they began training, but 37% indicated that exercise had helped them in smoking withdrawal. In keeping with their health-conscious attitude, 59% had regular medical check-ups, and 86% obeyed legislation requiring use of a seat belt when driving. In contrast with many older people, 88% slept well or very well. Slightly over half of the sample (57%) had sustained some injury which had limited their training for one or more weeks over the 7-year study. Although participation in Masters competition appears to carry considerable health benefits, gains may in part reflect an overall healthy lifestyle. PMID- 7788217 TI - The physiological demands of Gaelic football. AB - Match-lay demands of Gaelic football and fitness profiles were assessed at club competitive level. English Gaelic football club championship players (n = 11) were assessed for anthropometry, leg strength and time to exhaustion on a treadmill run. A similar test battery was administered to a reference group of University competitive soccer players (n = 12). Heart rate was recorded during match-play using radio telemetry and blood lactate concentrations were determined at half-time and after full-time. No differences (p > 0.05) were observed between the Gaelic and soccer players in: body mass (70.7 +/- 10.3 vs 76.6 +/- 10.3 kg); height (176 +/- 5.9 vs 177.7 +/- 6.4 cm); leg to trunk ratio (0.53 +/- 0.01 vs 0.54 +/- 0.03); adiposity (12.2 +/- 2.1 vs 13.5 +/- 3.2% body fat); mean somatotype (2.8 - 4.3-2.0 vs 2.4-4.2-2.4); leg strength measures; and performance on the treadmill. The percentage muscle mass values were lower for the Gaelic players compared to the soccer players (41.9 +/- 5.4 vs 47.3 +/- 5.2%; p > 0.005). For the Gaelic and soccer players, respectively, mean heart rate recorded during each half of match-play were (157 +/- 10 and 158 +/- 12 beats/min) and (164 +/- 10 and 157 +/- 11 beats/min), whilst blood lactates measured at the end of each half, were (4.3 +/- 1 and 3.4 +/- 1.6 mmol/l) and (4.4 +/- 1.2 and 4.5 +/ 2.1 mmol/l). Gaelic footballers at English club championship level seem to exhibit similar fitness profiles, and are subject to broadly similar physiological demands as University-level competitive soccer players. PMID- 7788218 TI - The estimation of body density in rugby union football players. AB - The general regression equation of Durnin and Womersley for estimating body density from skinfold thicknesses in young men, was examined by comparing the estimated density from this equation, with the measured density of a group of 45 rugby union players of similar age. Body density was measured by hydrostatic weighing with simultaneous measurement of residual volume. Additional measurements included stature, body mass and skinfold thicknesses at the biceps, triceps, subscapular and suprailiac sites. The estimated density was significantly different from the measured density (P < 0.001), equivalent to a mean overestimation of relative fat of approximately 4%. A new set of prediction equations for estimating density was formulated from linear regression using the logarithm of single and sums of skinfold thicknesses. Equations were derived from a validation sample (n = 22) and tested on a crossvalidation sample (n = 23). The standard error of the estimate (s.e.e.) of the equations ranged from 0.0058 to 0.0062 g ml-1. The derived equations were successfully crossvalidated. Differences between measured and estimated densities were not significant (P > 0.05), total errors ranging from 0.0067 to 0.0092 g ml-1. An exploratory assessment was also made of the effect of fatness and aerobic fitness on the prediction equations. The equations should be applied to players of similar age and playing ability, and for the purpose of identifying group characteristics. Application of the equations to individuals may give rise to errors of between 3.9% to +2.5% total body fat in two-thirds of cases. PMID- 7788219 TI - Implications of health and safety legislation for the professional sportsperson. AB - There are a large number of injuries in most professional sports every year, and research interest has usually centred around the medical aspects of these injuries. However, health and safety legislation also applies to professional sport, and it is important, as with any other occupation, to understand the underlying causes of the incidents leading to the injuries and to take steps to minimize future injuries. The introduction of the Management of Health and Safety at Work Regulations 1992 formalized a risk assessment approach to health and safety issues; an approach that has always been implicit in the Health and Safety at Work etc. Act 1974. This review assesses how the relevant UK health and safety legislation impacts on the professional sportsperson. PMID- 7788220 TI - Validity of conventional anthropometric techniques for predicting body composition in healthy Chinese adults. AB - There is little information on the application of generalized prediction equations to ethnic groups other than Europeans and groups of European descent. The purpose of this study was to crossvalidate conventional equations on a group of 56 Chinese adults. Body density was assessed by underwater weighing and also predicted by equations which use a combination of selected skinfolds-biceps, triceps, pectoral, subscapular, abdominal, suprailiac, thigh and calf. There were significant correlations (P < 0.01) between the various methods of predicting percentage fat. However, analysis of variance revealed significant differences (P < 0.01) between mean values. In the men, the Jackson and Pollock equation underestimated, and the Durnin and Womersley equation overestimated, the percentage fat predicted by underwater weighing. The best predictor site in this group was the medial calf skinfold (r = 0.81), which is not included in either equation. In the women, the best predictor sites were the triceps, suprailiac and thigh. As these sites are also used in the Jackson et al. equation, it is not surprising that there was no difference between the prediction of percentage fat by this equation and underwent weight. It is concluded that the Durnin and Womersley and Jackson and Pollock equations tend to overestimate and underestimate, respectively, the percentage fat in Chinese men. Alternative equations which use the calf skinfold may be more appropriate for this ethnic group. In Chinese women, there appears to be good agreement between Jackson and Pollock and hydrodensitometric estimations of percentage fat. PMID- 7788221 TI - Rating of perceived exertion and heart rate relative to ventilatory threshold in women. AB - Forty women took part in a study designed to investigate self-selected exercise intensity relative to ventilatory threshold during circuit weight training (CWT) and exercise-to-music (ETM) sessions. Subjects were assigned to one of two groups which were beginners (B) or habitual exercisers (HE) on the basis of their exercise habits. All subjects first underwent a laboratory cycle ergometer test involving a continuous incremental exercise protocol from which ventilatory threshold (VT) was determined using piecewise linear regression analysis. This point was expressed in terms of heart rate (VTHR) and rating of perceived exertion (VTRPE). These points were then compared with those determined during exercise training sessions (TRAHR and TRARPE respectively). The results showed that mean(s.d.) TRARPE (13.5(1.1) was not significantly different to mean(s.d.) VTRPE (12.8(0.5); P > 0.05) but that mean(s.d.) VTHR (134.8(13.5) beats min-1) and TRAHR (154.9(12.0) beats min-1) were different (P < 0.05). Beginners trained at a significantly higher percentage above VTHR than habitual exercisers (118(3.1) versus 111(2.8)% P < 0.05). During CWT the mean(s.d.) TRAHR for beginners (143.2(7.6) beats min-1) was significantly lower than that for habitual exercisers (152.5(10.1) beats min-1; P < 0.05), but not different during ETM (P < 0.05). When these TRAHR values were expressed relative to an estimated maximum heart rate (EMHR) they represented 86.5% in ETM and 80.5% in CWT which were different (P < 0.05). These results suggest that regardless of habitual exercise level and training mode, these women selected a common intensity of effort that was compatible with the described RPE. PMID- 7788222 TI - Leucocyte and erythrocyte counts during a multi-stage cycling race ('the Milk Race'). AB - Venous blood samples were taken from eight competitors in mid-evening after a racing day, and in the early morning before the next day's race, three times during the course of the Milk Race, 1992. These were used to gather information about the changes in circulating leucocyte levels in response to the exceptionally high sustained daily workload required during a major multi-stage race. The primary objective was to provide knowledge of 'normal' values against which future clinical judgements of abnormality might be made in these unusual circumstances. During the race, estimated energy output was about 25 MJ (6000 kCal)/day. The mean total circulating leucocyte numbers (per litre of blood), and those of individual leucocyte classes (neutrophil, lymphocyte, monocyte, eosinophil and basophil) were all inside the normal range both in the morning and in the evening. Evening counts were, however, 30-50% higher than morning counts, for all classes except eosinophils. We conclude that individual clinical decisions about leucocyte levels can best be made using normal (sedentary man) values if a morning sample is taken. PMID- 7788224 TI - Sports medicine on the line? PMID- 7788223 TI - Reproducibility of cardiorespiratory measurements during submaximal and maximal running in children. AB - With the increased use of oxygen consumption measurements in clinical and sporting studies, measurement variability has become more important to both the paediatric clinician and the sports scientist. In this study we assessed the reproducibility of cardiorespiratory measurements during submaximal and maximal running in children. Ten healthy, physically active boys (mean(s.d.) age 10.7(0.71) years) performed two submaximal and two maximal running tests within a 4 week period. The submaximal protocol consisted of three 6 minute runs at 7.2, 8.0 and 8.8 km/h. Every attempt was made to minimize the sources of non biological variability at each testing session. During submaximal exercise, oxygen consumption (VO2), heart rate (HR) and fractional utilization appeared to be the most reliable measures accounting for over two-thirds of the total variation (coefficients of reliability (CR) of 68%, 94% and 82% respectively). Ventilation (Ve) and respiratory exchange ratio (RER) proved to be only moderately reliable accounting for less than half of the total variation (CR 50% and 45% respectively). At maximal exercise, VO2, Ve and time to exhaustion were most reliable, accounting for approximately two-thirds of the total variation (CR 65%, 63% and 63% respectively). Within this test environment, a two visit submaximal assessment was capable of estimating VO2 with a standard error of +/- 1.25 ml/kg/min. Similarly, for maximal testing a two visit assessment estimated peak VO2 with a standard error of +/- 2.28 ml/kg/min. On the evidence of these results a two visit assessment for submaximal and maximal exercise testing seems adequate to estimate the stability of submaximal cardiorespiratory measures and peak VO2 in healthy, normally active boys. PMID- 7788225 TI - Some experiments upon the biological effects of fast neutrons. 1940. PMID- 7788226 TI - Predicting local recurrence by correlating pre-operative mammographic findings with pathological risk factors in patients with breast cancer. AB - The pre-operative mammograms for 231 patients undergoing conservation surgery for breast cancer between March 1988 and September 1992 were analysed for features that may predict the presence of pathological risk factors of local recurrence (residual microscopic disease, extensive intraduct carcinoma (EIC) and lymphatic/vascular invasion). Residual microscopic disease was detected in 40% of patients and was associated with a DY mammographic pattern (p = 0.03), casting calcification (p = 0.0002) and absence of mammographic nidus (p = 0.0006). Residual microscopic disease was found in 75-88.9% of patients when two of these preoperative mammographic features were present in combination. The mean lumpectomy diameter was significantly smaller for patients with DY compared to N1 mammographic pattern on Wolfe grade (p = 0.039). Both residual disease and Wolfe grade were related to age (p = 0.0032 and p < 0.0001). EIC was found in 22% of patients and was associated with casting (p < 0.0001) and non-casting (p = 0.04) calcification, absence of mammographic nidus (p < 0.0001) and stellate mammographic nidus (p = 0.02). No significant association was found between mammographic features and lymphatic/vascular invasion. Pre-operative mammographic features can predict patients likely to have residual microscopic disease or EIC following conservation surgery for breast cancer. These patients should be selected for wider primary excision. PMID- 7788227 TI - Mammographic features of invasive lobular and invasive ductal carcinoma of the breast: a comparative analysis. AB - The mammographic appearances of 86 invasive lobular carcinomas were compared with those of 86 invasive ductal carcinomas of no special type matched for age, size and stage. There was no significant difference in the frequency of a mammographic abnormality consistent with malignancy between the lobular carcinoma (90%) and ductal carcinoma (96%) groups. A spiculate mass was the commonest feature in both groups (69% and 63%, respectively). There were no differences in the imaging features of masses in the two groups. In the lobular carcinoma group any mammographic abnormality was more likely to be seen on only one view and calcifications were less frequently observed. Multiple lesions were more frequent in the ductal carcinoma group. However, although these differences appeared to reach statistical significance, as they were only apparent in a study with a large number of comparisons, it is unlikely that these differences are practically significant. Analysis of the lobular invasive group failed to demonstrate any significant differences in the imaging features of the classical and mixed sub-types, a spiculate mass being the most common single abnormality in both. No mammographic differences of practical use to distinguish invasive lobular from invasive ductal carcinoma of no special type were demonstrated. PMID- 7788228 TI - Ultrasound of the Achilles tendon after surgical repair: morphology and function. AB - Ultrasound is a well established method for the examination of the Achilles tendon. The objective of the study was to provide answers to the following questions: What ultrasonographic structural changes are long lasting after surgical repair? How important is ultrasound with regards to the functional evaluation of late results? 60 patients were examined at an average 11 years (2 19) after surgical repair of Achilles tendon rupture. In only four patients sonographic morphology of the tendon was according to the non-injured side. A variety of distinct basic alterations in ultrasound morphology was found: a hypoechogenic ribbon ventrally to the dorsal paratenon (n = 40), spots of hypoechogenic areas in the tendon (n = 18), dishomogeneous hyperechogenicity with preservation (n = 12) or dissolving (n = 22) of its fibrillar components along the longitudinal axis. In most of the cases the paratenon was thickened or could not be differentiated. In the dynamic ultrasound examination gliding mechanism of the achilles tendon was limited in 41 patients. Extensive functional subjective and objective parameters of all patients were evaluated in an Achilles tendon score. The results were rated as excellent (n = 18), good (n = 29), satisfactory (n = 12) and poor (n = 1). There was no statistical correlation between ultrasound morphology and clinical outcome. Therefore, it was concluded that ultrasound examination is able to reveal long-lasting alterations in echogenicity of the tendon but is only of limited value with regards to evaluation of the functional results after surgical repair. PMID- 7788229 TI - Prediction of gall stone composition by ultrasound: implications for non-surgical therapy. AB - Oral cholecystography is the basic radiodiagnostic procedure required to assess chemical composition of gallstones as well as functional status of gall bladder prior to non-surgical management of gallstones. However, the value of ultrasound in non-surgical management of gallstones is yet to be proved. In this study we attempt to establish sonographic criteria which will predict the composition of gallstones prior to their non-surgical treatment. For this purpose the ultrasonographic characteristics of 233 patients with gallstone disease and functioning gall bladders were studied and an effort was made to correlate cholesterol and calcium content of different types of stones (as estimated by X Ray powder diffraction study and atomic absorption spectrophotometry) with their ultrasonographic characteristics. Sonographic criteria for the presence of cholesterol stones were those which were floating and gallstones producing acoustic shadowing without internal echoes from within the stone. In detecting findings which would predict the presence of cholesterol stones on ultrasound, ultrasound had a sensitivity of 72.90% and a specificity of 100%. The predictive values of positive findings and negative findings were 100% and 93.4%, respectively. The demonstration of typical features of cholesterol stones on ultrasound obviates the need for oral cholecystography. PMID- 7788230 TI - Magnetic resonance imaging in the detection of focal liver lesions: comparison of dynamic contrast-enhanced TurboFLASH and T2 weighted spin echo images. AB - In a previous study using dynamic contrast-enhanced TurboFLASH (DCETF) for demonstration of the portal venous system we found that this technique showed more liver lesions than T2 weighted spin echo (T2WSE) imaging in the same patients. In this study we have formally compared axial T2WSE images (TR 2000, TE 45/90) with TurboFLASH images (TR 135, TE 4, FA 80 degrees) acquired immediately after bolus injection of Gd-DTPA (0.1 mmol kg-1) in 41 patients referred for hepatic magnetic resonance imaging (MRI) prior to surgery for liver lesions. The images of each sequence were independently reviewed by two observers. The lesions were counted and each sequence was scored for conspicuity, level of artefact and subjective image quality. Contrast-to-noise ratios using user defined regions of interest were calculated. Significantly more lesions were seen on DCETF (n = 186) images than on T2WSE (n = 123) images (p < 0.001). Lesion conspicuity was equal in 53% of cases, better on DCETF in 36% and better on T2WSE in 11%. Contrast-to noise ratios were significantly higher on DCETF images (p < 0.05). DCETF imaging provided a substantial improvement in lesion detection compared with T2WSE imaging. PMID- 7788231 TI - Measurement of human pancreatic perfusion using dynamic computed tomography with perfusion imaging. AB - Absolute quantification of pancreatic perfusion in man has been extremely difficult to date. This paper describes a relatively simple application of dynamic computed tomography to provide perfusion imaging of the human pancreas. Values for perfusion in eight normal pancreases ranged between 1.25 and 1.66 ml min-1 ml-1 (mean: 1.52 ml min-1 ml-1). Increased perfusion values were present in a patient with an islet cell tumour (overall perfusion 2.11 ml min-1 ml-1) and a patient with Wilson's disease (3.43 ml min-1 ml-1). Pancreatic perfusion was reduced in a patient with diabetes (0.60 ml min-1 ml-1) and in a failing pancreatic transplant (0.97 ml min-1 ml-1). The combination of functional information and good spatial detail afforded by computed tomography (CT) perfusion imaging means the technique is well suited for the evaluation of the human pancreas. It is currently the only technique which allows non-invasive absolute quantification of pancreatic perfusion. PMID- 7788232 TI - Ultrasound in the evaluation of osteoporosis: a comparison with bone mineral density at distal radius. AB - It is proven that, from a technical point of view, ultrasound transmission velocity (UTV) measurement can easily be taken at the distal end of the radius. The reproducibility of UTV is good (coefficient of variation 0.3% intraoperator and 0.5% interoperator). 248 normal and 65 osteoporotic women were then studied to establish the range of UTV values and to compare the ability of UTV and bone mineral density (BMD) measurement, taken at the same skeletal sites, to detect osteoporotic fragility. Osteoporosis was defined by the presence of atraumatic vertebral fractures on an X-ray of the spine. Ultrasound velocity averaged 1570.5 +/- 43.3 m s-1 in normal and 1519.2 +/- 15.2 m s-1 in osteoporotic women; the difference is also statistically significant (p < 0.01) for BMD. Both BMD and UTV decline after menopause and are significantly correlated with age. A weak correlation (r = 0.68) was found between UTV and BMD; this supports the thesis that ultrasound velocity measures bone mass as well as other fragility components of bone distinct from the decrease of mass. Receiver operating characteristic (ROC) curve analysis showed that UTV discriminates between normal and osteoporotic patients at least as well as radial BMD, indicating that UTV is a new available diagnostic modality which can be used to screen osteoporotic subjects. PMID- 7788234 TI - Entrance doses during lateral lumbar spine and antero-posterior abdomen examinations: generator waveform dependence. AB - In North Trent, UK, an entrance dose survey of lateral lumbar spine and antero posterior (AP) abdomen examinations has been carried out in 17 radiology departments. The survey comprised 294 lateral lumbar spine and 322 AP abdomen entrance dose measurements. The mean entrance doses were found to be approximately half of the relevant national reference entrance dose levels of 30 mGy and 10 mGy, respectively. The effect of generator waveform on entrance dose was studied by separating the generators into two types: "pulsating potential" (PP) generators and "constant potential" (CP) generators for each examination. PP generators comprised 23% of the total number of examinations. The mean entrance dose and radiographic exposure factors from CP generators were found to be significantly lower than those from PP generators. The use of CP type generators, together with low attenuation components can significantly reduce patient entrance doses for these examinations. PMID- 7788233 TI - Dosimetric considerations in 131I-MIBG therapy for neuroblastoma in children. AB - Dosimetric calculations have been made for organ doses in patients receiving 131I MIBG therapy as treatment for neuroblastoma. As well as whole body and liver dose, consideration has been given to dosimetry of organs (lung, urinary bladder) whose tolerance may become treatment limiting when 131I-MIBG is given as part of combined modality therapy. Data from both adults and children receiving radiolabelled MIBG for diagnostic or therapeutic purposes have been compared in constructing dosimetry models for children. A recently published urodynamic model has been used in the estimation of radiation dose to the bladder. The results show that liver and lung may receive doses greater than the average total body dose (0.58 mGy MBq-1 and 0.35 mGy MBq-1, respectively, as compared with 0.25 mGy MBq-1 to the whole body). The organ dose estimates do not differ greatly from previous analyses except in the case of the bladder for which the new modelling studies have resulted in lower dose estimates (0.76 mGy MBq-1 administered, for dose to bladder surface from bladder contents) than in some published series. This may result from differing assumptions regarding parameters such as bladder content and urine flow rate, an enhanced fluid intake being assumed in the present bladder dose estimates. Average doses to the bladder wall from the contents were estimated to be 7.4-11.3% of the surface doses. The urodynamic modelling analysis shows that the bladder could receive a much greater dose (by an order of magnitude) in patients who were inadequately hydrated or had impaired renal function. PMID- 7788235 TI - Patient and staff dosimetry in neuroradiological procedures. AB - Cerebral angiography provides valuable information for use in the clinical management of patients but can result in relatively high radiation doses to patients and staff due to the extended fluoroscopy time and number of images acquired during an examination. In this study, extremity doses to radiologists and scrub nurses working in a neuroradiological centre were monitored during a 3 month period using thermoluminescent dosemeters (TLDs). Electronic personal dosemeters were also used to monitor doses above the lead apron at chest height to the radiologists, radiographers and the scrub nurses. Patient doses were recorded using a dose-area product meter whilst patient thyroid dose was measured using TLDs. Two types of examination were studied: cerebral angiography and arterial embolization. It was deduced from the results of the study that the radiologist may expect to receive a mean dose above the lead apron at chest height of 11 microSv and 25 microSv per examination when performing cerebral angiography and arterial embolization, respectively. A radiologist mean hand dose of 19.3 microSv per examination was found, whilst the average eye dose for both radiologist and scrub nurse was 13.4 microSv per examination. The patient dosimetry results revealed a mean thyroid dose of 1.7 mSv and a dose-area product of 48.5 Gy cm2 for cerebral angiography. Average dose-area product for arterial embolization was 122.2 Gy cm2 along with a mean patient thyroid dose of 3.3 mSv. More detailed patient dosimetry was also performed using a Rando anthropomorphic phantom loaded with TLDs to measure organ doses and hence estimate effective dose. A typical four vessel angiogram was found to result in a patient effective dose of 3.6 mSv. PMID- 7788236 TI - Assessment of organ radiation doses and associated risk for digital bifemoral arteriography. AB - An assessment has been made of the absorbed dose associated with femoral arteriography using a digital imaging system. A bilateral femoral arteriogram was performed on 17 patients, using a filmless 1024 matrix digital image acquisition system with a discrete stepping tube-stand and 40 cm image intensifier. A standardized protocol of manual patient/tube-stand positioning under fluoroscopic control and automatic stepping digital acquisition was followed. Skin entry doses were measured with a dose-area product meter for each stage of the procedure, and the total gonad dose was assessed with thermoluminescent dosimeters (TLDs). Published Monte Carlo simulations were supplemented with further calculations to evaluate organ doses from the dose-area products measured. Comparison with the TLD measurements indicated that this technique over-estimated organ doses by about 30%. A mean effective dose of 3.1 +/- 1.8 mSv was calculated for the procedure, with the greatest dose burden being imposed by fluoroscopy during catheter manipulation. The related radiation detriment is 0.018%, which is insignificant when compared with the overall mortality from peripheral vascular disease. PMID- 7788237 TI - Analysis of patient doses for myelogram and discogram examinations and their reduction through changes in equipment set-up. AB - Patient doses for myelogram and discogram examinations performed on two C-arm X ray units have been measured using dose-area product meters. Contributions to the dose from fluoroscopy and radiography have been obtained from analysis of results for a selection of examinations. Information was recorded about the individual beam projections used, in order to allow estimates of effective dose. Effective doses for lumbar myelograms were 3-4 mSv and for cervical myelograms and discograms were 1 mSv. The doses on the two units were similar, but contributions from the various parts of the examinations were different. Quality assurance (QA) measurements of dose variables were used to determine reasons for these differences in performance. Fluoroscopic doses are influenced by image intensifier dose rate and by the way in which exposure factor selection has been set up for the automatic exposure control (AEC) system. Doses from digital fluorography on units for specialized applications may be greater than those with standard film/screen systems. Recommendations have been made concerning ways in which doses on each unit might be reduced. Detailed assessments of doses resulting from AEC set-up options, made during QA tests, can help to ensure that the optimum balance between patient dose and image quality is achieved. PMID- 7788238 TI - Technical note: compression stockings and posture: a comparative study of their effects on the proximal deep veins of the leg at rest. AB - Graduated compression stockings have been shown to reduce the incidence of deep venous thrombosis. While they are thought to act primarily by increasing venous flow velocity, their mode of action remains uncertain. Doppler ultrasound was employed to study the relative effects of three types of support stocking on the deep venous diameter, flow velocity and pulsatility in 10 non-pregnant female subjects. In addition, the effect of altered posture on the same parameters was assessed. Significant effects of the graduated stockings were found at the level of the popliteal vein, where a reduction in both the diameter and the amplitude of respiratory phasicity was recorded (p < 0.05). No significant increase in flow velocities was recorded. Adopting the left lateral position significantly increased flow velocity in the right common femoral vein (p < 0.05). The application of stockings in this position produced no additional increase in flow velocities, but did alter the amplitude of respiratory phasicity. These data do not support the widely held view that graduated compression stockings increase flow velocities at rest. Adopting a lateral recumbent position significantly increases flow velocity in the non-dependent leg. PMID- 7788239 TI - Technical note: maxillofacial biomodelling--preliminary result. AB - A new technique of manufacturing three-dimensional (3D) hard tissue biomodels is described. The models, derived from computed tomography data, were constructed by a computer-controlled manufacturing device known as stereolithography apparatus (SLA). Selected cases of patients with facial deformities were presented to illustrate clinical applications of the SLA biomodelling. Physical demonstration of the bony internal anatomy in these patients promoted better conceptualization of the disease process, allowing optimal input into the management decision, pre operative planning and choice of surgical technique with a consequent reduction in operating time and potential reduction in peri-operative morbidity. Limitations of the solid modelling technique include cost, a lengthy production time which renders it unsuitable for emergency cases, and radiation exposure of the patient. With wider use and further technological development, these drawbacks will be minimized. The 3D SLA biomodels may in future become an adjunct, not only to maxillofacial surgery, but also to other medical specialties. PMID- 7788240 TI - Technical note: a radiological education system--organization of an image library. AB - A successful radiological library and teaching system should be easy to compile, user-friendly, dynamic and flexible. Nowadays it must be amenable to incorporation into digitally-based communication systems such as personal computers (pc) and picture archiving and communication systems (PACS). This article describes the structural organization and capabilities of such a digital radiological education system, and demonstrates how it fulfils these aims. PMID- 7788241 TI - Technical note: digital radiographic pelvimetry--a novel, low dose, accurate technique. AB - A technique is described for lateral pelvimetry which results in a lower radiation dose than that resulting from conventional film-screen pelvimetry and computed tomography (CT) pelvimetry. It uses digital radiographic imaging thereby closely matching conventional techniques yet additionally providing post processing facilities including distance measurement and contrast adjustment. The digital technique was evaluated with an anthropomorphic phantom and compared with the conventional technique by measuring entrance surface doses on two groups of post-natal patients. Digital radiography gave radiation doses 10 times lower than those using conventional techniques. PMID- 7788242 TI - Case report: computed tomography in the investigation of bilateral mandibular coronoid hyperplasia. AB - Bilateral mandibular coronoid hyperplasia is characterized by restricted mouth opening due to impingement of the coronoid processes on the zygomatic arches. The condition is unfamiliar to many clinicians and may be significantly under reported. The presented case highlights the benefits of computed tomography (CT) in the diagnosis and surgical evaluation of this disorder. PMID- 7788243 TI - Case report: septic arthritis of the hip following ureteric stent insertion. AB - Urinary infection is a recognized complication of ureteric stent insertion. We present a case of pelvic abscess and avascular necrosis of the hip following insertion of a stent for ureteric obstruction. PMID- 7788244 TI - Case report: volvulus of the splenic flexure in a patient with systemic sclerosis. PMID- 7788245 TI - Case report: variable imaging appearances of angiomyolipomas of the liver. AB - Angiomyolipomas of the liver are rare benign tumours. We describe the variable imaging appearances of these tumours in three women. The first two patients underwent ultrasound, computed tomography (CT) and angiography, which demonstrated lesions resembling focal nodular hyperplasia and hepatocellular carcinoma, respectively. Both had histologically-proven liver angiomyolipomas surgically resected. The third patient was incidentally found to have typical features of multicomponented liver angiomyolipoma on CT. Variable proportions of fatty tissue in these tumours are the most likely explanation for their different imaging appearances on CT. PMID- 7788246 TI - Case of the month: " ... or plat du jour". PMID- 7788247 TI - Contrast media, endothelin, angioplasty and restenosis. PMID- 7788249 TI - Ketoprofen in Pain. Proceedings of Actron International Experts Meeting. Interlaken, Switzerland, 20-23 March 1994. PMID- 7788250 TI - Nocturnal enuresis. AB - Nocturnal enuresis is common. Although its aetiology remains unclear recent evidence increasingly supports the lack of a normal nocturnal increase in ADH leading to nocturnal polyuria exceeding functional bladder capacity. Sleep patterns are probably normal although an arousal disorder might be a factor. Treatment should follow careful evaluation to determine if one is dealing with 'uncomplicated' or 'complicated' enuresis. Complicated enuresis requires further investigation. 'Uncomplicated enuresis' always requires reassurance and patient and parent education. Resource centres such as ERIC can provide information and advice. Active treatment should be tailored to the patients age, motivation and parental wishes. Behavioural modification techniques yield the highest long-term cure rate but require the most commitment and are rarely successful before the age of 7-8 years. Pharmacotherapy has been revolutionized by DDAVP which gives a response rate of up to 70% relatively free from side-effects but at the price of a high relapse rate after medication. Imipramine is less expensive than DDAVP but may be fatal in overdose. Anticholinergics should be reserved for those patients with significant diurnal symptoms or those who fail first-line pharmacotherapy. Overall patients and parents should be reassured by the high spontaneous cure rate. PMID- 7788251 TI - Extracorporeal piezoelectric shock wave lithotripsy as mono and multiple therapy of large renal calculi including staghorn stones in unanaesthetized patients under semi-ambulant conditions. AB - OBJECTIVE: To examine the effectiveness and complication rate of extracorporeal piezoelectric shock wave lithotripsy (EPL) as monotherapy for the treatment of large renal calculi. PATIENTS AND METHODS: Treatment consisted of semiambulant EPL as monotherapy combined with protective ureteric stenting in 84 patients. Three groups were established according to stone volume (borderline-stone, partial and complete staghorn). An average of 18,230 shock waves was applied in 3.76 sessions to each patient. RESULTS: No major complications were observed but there were minor complications in 33% of patients. Invasive auxiliary methods were necessary in only 12%. After a mean follow-up of 9 months (n = 72), 54% of patients were stone-free and in 22% the fragments passed spontaneously. Thus the success rate was 76%. Analysis of the three groups showed no difference in stone status during follow-up. There was no relation between the outcome of treatment and stone volume. Analysis of the patients who failed to respond to treatment showed that they were treated for longer than the stone-free group, with significantly fewer sessions per week (0.71 vs 1.28 sessions/week). It appears that higher rates of stone removal can be achieved with more frequent treatment sessions at shorter intervals. CONCLUSION: We consider semi-ambulant EPL monotherapy to be a minimally invasive alternative treatment in patients with large renal calculi, including staghorn stones. PMID- 7788252 TI - Involvement of the inferior vena cava by renal tumour: surgical excision using hypothermic circulatory arrest. AB - OBJECTIVE: To evaluate the immediate and long-term results of a radical surgical technique in the treatment of renal tumours with extensive involvement of the inferior vena cava (IVC). PATIENTS AND METHODS: Seven patients with extensive involvement of renal tumours into the IVC were operated upon using a cardiopulmonary by-pass, hypothermia and cardiac arrest to facilitate surgery. Wide exposure of the IVC in a bloodless field permitted complete removal of all visible tumour in each case. Histological sections confirmed renal cell cancer in six patients and Wilms tumour in a 15-year-old girl. RESULTS: All patients recovered well from their surgery with no major complications and spent one or two days in the Intensive Treatment Unit and an average of 13 days in hospital after the operation. Of the seven patients, four are alive and well with no obvious disease after an average follow-up time of 30 months (range 8-54). The other three patients have died from disseminated renal cancer. CONCLUSION: This procedure provides good local control of the tumour and offers the only hope of cure in patients with this disease. In collaboration with the surgical cardiac team it can be safely carried out with acceptable morbidity and mortality. PMID- 7788248 TI - Potential gonadal dose from leakage radiation? PMID- 7788253 TI - Surgery of lung metastases in renal cell carcinoma. AB - OBJECTIVE: To examine the impact on survival of pulmonary resection in the treatment of renal cell carcinoma that has metastasized to the lung. PATIENTS AND METHODS: From June 1986 to July 1991, 19 patients were submitted to synchronous or asynchronous lung metastasectomy. Histological examination confirmed the presence of lung metastases from renal cell carcinoma in 16 cases (six synchronous and 10 asynchronous with a mean disease-free interval of 23 months). In the other three cases, histological examination revealed tuberculomas, chondroid hamartoma and foci of anthracosis. RESULTS: To date, among the six patients with synchronous lung metastases, three have died, two are progressing and one has no evident disease after a mean survival of 24 months. Among the 10 patients who underwent surgical resection of metachronous lung metastases, one has died, three are progressing and six have no evident disease (mean survival time, 43 months). CONCLUSION: While the presence of synchronous lung metastases is an unfavourable prognostic factor even after surgical removal (five out of six patients died or are in progression shortly after metastasectomy), the results after surgery of asynchronous lung metastases are encouraging, although the real efficacy of this treatment is still to be confirmed. PMID- 7788254 TI - Different susceptibilities of lymphokine-activated killer cells (LAK cells) among primary and metastatic renal cell carcinoma derived from the same patient. AB - OBJECTIVE: To investigate the susceptibility of primary renal cell carcinoma (RCC) and metastatic RCC to lymphokine-activated killer (LAK) cells using three RCC cell lines derived from the primary and metastatic tumours in a male patient with advanced RCC. MATERIALS AND METHODS: Three RCC cell lines (named HANKS) were derived from a 44-year-old man with advanced RCC. HANKS-Pr, HANKS-Lu and HANKS-LN were established from the primary lesion and the metastatic lung and lymph node lesions, respectively. The susceptibility of HANKS cell lines to 18 different LAK cells obtained from either patients with urological cancer or from healthy volunteers was studied. The three groups of LAK cells were divided as follows: (A) LAK cells from RCC patients (n = 6); (B) LAK cells from patients with transitional cell carcinoma (TCC)/prostatic carcinoma (CaP) (n = 4) and (C) healthy volunteers (n = 8). A 51Cr-releasing cytotoxic assay was used to determine susceptibility. RESULTS: The mean percentage lysis of the HANKS cell lines to the 18 allogenic LAK cells were 28.1% in HANKS-Pr, 20.2% in HANKS-Lu and 10.4% in HANKS-LN. The susceptibility of HANKS-LN to LAK cells was significantly lower than that of HANKS-Pr and HANKS-Lu in all three groups (P < 0.05). In contrast, the susceptibility of HANKS-Pr was significantly higher than HANKS-Lu in group A only (P < 0.01). CONCLUSION: This is the first report to describe the different susceptibilities of primary RCC and metastatic RCC derived from the same patient. HANKS-LN itself might be the least susceptible to LAK cells because it was not related to the source of LAK cells. Furthermore, RCC may affect the cytotoxicity of LAK cells to HANKS-Pr. These data indicate there are at least two different types of mechanisms leading to the different susceptibilities of HANKS cells to LAK cells. PMID- 7788256 TI - Should Stamey colposuspension be our primary surgery for stress incontinence? AB - OBJECTIVE: To evaluate the outcome of the Stamey procedure for stress incontinence and to decide if it is an acceptable first-line option for the treatment of patients. PATIENTS AND METHODS: Between June 1987 and March 1993 67 women had Stamey bladder neck suspension carried out for the treatment of stress incontinence. In September 1993 all patients received a detailed questionnaire to ascertain their present status. RESULTS: Immediately after surgery 70% of patients were dry and 15% were much improved. At 6 months 56% of patients were dry and 21% were much improved. More than 1 year following surgery, of 58 patients responding only 31% were dry and 28% were much improved. More than 5 years after surgery only 18% of the 28 women responding were dry. The factors which were significantly associated with failure were obesity (P < 0.005) and the number of pads used per day (P < 0.05). Previous surgery may also be an important factor. CONCLUSION: The Stamey vesical neck suspension has a good early success rate but the results in the longer term are not acceptable. This operation should not be used as a first-line treatment for stress incontinence and should be reserved for specific patient subgroups. PMID- 7788255 TI - Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia. AB - OBJECTIVE: To compare trospium chloride (TCl), a quaternary ammonium derivative with atropine-like effects and predominantly antispasmodic activity, with oxybutynin (Oxy) in terms of efficacy and adverse effects. PATIENTS AND METHODS: In a randomized, double-blind, multicentre trial, 95 patients with spinal cord injuries and detrusor hyper-reflexia were studied. Treatment consisted of three doses per day over a 2 week period, with either Oxy (5 mg three times daily) or with TCl (20 mg twice daily) with an additional placebo at midday. The results were evaluated with regard to changes in objective (urodynamic) data and subjective symptoms as well as the incidence/severity of adverse effects. RESULTS: With both drugs there was a significant increase in maximum bladder capacity, a significant decrease in maximum voiding detrusor pressure and a significant increase in compliance and residual urine; there were no statistically significant differences between the treatment groups. The percentage of patients who reported severe dryness of the mouth was considerably lower (4%) in those receiving TCl 2 x 20 mg/day than in those receiving Oxy (23%) 3 x 5 mg/day. Withdrawal from treatment was also less frequent in those receiving TCl (6%) than in those receiving Oxy (16%). CONCLUSION: Trospium chloride and oxybutynin, judged in terms of objective urodynamic parameters, are of substantially equal value as parasympathetic antagonists. However, assessment of tolerance in terms of adverse drug effects showed that TCl had certain advantages. PMID- 7788257 TI - Ploidy and Tn-antigen expression in the detection of transitional cell neoplasia in non-tumour-bearing patients. AB - OBJECTIVE: To study the effectiveness of combining DNA ploidy and the blood-group related membrane antigen Tn as bladder tumour markers which have been individually associated with high tumour grade and poor prognosis. In particular to (i) determine whether use of these two markers would improve tumour detection compared with either alone, particularly of high grade disease and (ii) determine whether intermediate rates of marker expression would occur in bladder cancer patients with no current tumour compared with those with a tumour and a control group with benign prostatic hypertrophy. PATIENTS AND METHODS: A total of 102 patients undergoing cystoscopic monitoring for either benign prostatic hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Repatriation Hospital and Flinders Medical Centre were included in the study. The patients comprised three study groups, those with BPH (n = 37), with TCC but no tumour present (n = 38) and those with TCC and a tumour present at cystoscopy (n = 27). Exfoliated cells obtained from bladder washings at cystoscopy were double labelled using a monoclonal antibody to the Tn antigen and a DNA stain, propidium iodide and examined by flow cytometry. RESULTS: Rates of marker expression in 27 patients with tumours were 30% for Tn antigen, 30% for aneuploidy and 48% for either marker. Marker expression was strongly associated with tumour grade, with no expression at grade 1, 38% (3/8) tumours at grade 2 and 90% (9/10) at grade 3. In patients with a history of bladder tumours but no current tumour, rates were intermediate (30%) compared with patients with current transitional cell carcinoma (42%) and control patients (19%). CONCLUSION: The use of Tn antigen combined with DNA flow cytometry can increase tumour detection, particularly of high grade, aggressive disease. Gradation of expression of these markers across patient groups at increasing risk of a tumour, with intermediate expression in patients with no current tumour, suggests that marker expression may be detecting a preneoplastic stage of the disease, which is not possible with cytology. Given two parallel disease processes for superficial papillary and for high grade disease with invasive potential, the expression of high grade tumour markers in cells from cystoscopically normal bladders may represent a pre-clinical stage of aggressive disease. The identification of patients at risk of invasive disease using combinations of tumour markers may offer advantages in clinical management, particularly when no tumour is present and therefore no histopathological assessment is made. PMID- 7788258 TI - Numerical chromosome aberrations in bladder cancer detected by in situ hybridization. AB - OBJECTIVE: To investigate the relationship between interphase cytogenetics and the grade and stage of bladder cancer in patients with transitional cell carcinomas of the urinary bladder. PATIENTS AND METHODS: By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 10, 11, 17, 18, X and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded sections of the routinely processed bladder cancers from 20 patients. The percentage of hyperdiploid cells (three or more spots) was estimated using light microscopy. RESULTS: The percentage of hyperdiploid cells for chromosomes 7, 11 and 17 was highly correlated with increasing tumour grade (P < 0.01, Spearman rank correlation) or increasing pathological stage (P < 0.01). The percentage of hyperdiploid cells for chromosome Y was not correlated with either grade or stage (P > 0.05). As high tumour grade and stage are both indicative of more aggressive tumour behaviour and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosomes 7, 11 and 17, may be highly predictive of bladder tumour aggressiveness. CONCLUSION: These preliminary results suggest that measurement of numerical chromosome aberrations using in situ hybridization in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours. PMID- 7788259 TI - Is there a role for in vivo methylene blue staining in the prediction of bladder tumour recurrence? AB - OBJECTIVE: To assess the role of in vivo staining with intravesical methylene blue in predicting tumour recurrence. PATIENTS AND METHODS: Thirty-nine patients (27 men and 12 women, age range 43-75 years) newly diagnosed with bladder tumours were prospectively studied and followed for a minimum of 2 years. Potential biopsy sites were identified by staining intravesically with a 1% methylene blue solution and compared with random biopsy sites. RESULTS: Biopsy directed by methylene blue staining detected carcinoma in situ more often than random biopsy. Rates of recurrence were similar in both stained and unstained groups. CONCLUSION: Methylene blue staining does not add significantly to the management of patients presenting with bladder tumours. PMID- 7788260 TI - Correlation of morphometry, nucleolar organizer regions, proliferating cell nuclear antigen and Ki67 antigen expression with grading and staging in urinary bladder carcinomas. AB - OBJECTIVE: To investigate the correlation of four different indicators of proliferation--mean nuclear area (MNA) morphometry, nucleolar organizer region (NOR) count, proliferating cell nuclear antigen (PCNA) and Ki67 antigen expression--in specimens of invasive and non-invasive urinary bladder carcinomas with the grading and staging of the tumour and to determine which indicator is most suitable for discriminating between non-invasive and invasive carcinomas. MATERIALS AND METHODS: Biopsies of 58 urinary bladder carcinomas of different grade and stage (38 invasive, 20 non-invasive) and 11 carcinomata in situ were included in the study. Ten specimens of normal bladder mucosa served as controls. Analysis of indicators was performed on sequential serial paraffin sections of the same tissue, applying each test once to one of four serial sections. RESULTS: In comparison to normal bladder mucosa the values of the four indicators were significantly greater (P < 0.001) in all carcinomata in situ and in carcinomas. Values also increased from grade 1 to grade 3 carcinomas, but indicator values were similar for carcinomata in situ and grade 2 carcinomas. All indicators correlated with each other and allowed a significant discrimination between grade 1 and 2 or grade 2 and 3 carcinomas. Non-invasive carcinomas (Ta) showed a significantly lower proliferative activity (P < 0.001) than invasive carcinomas but there were overlapping values within the invasive carcinomas (T1,T2 and T3/4). CONCLUSIONS: MNA, NOR count, PCNA index and Ki67 index could be correlated with tumour grade, but not with stage, of transitional bladder carcinoma. Of the indicators studied the Ki67 antigen was the most useful in differentiating between invasive and non-invasive carcinomas. This could be of prognostic relevance, especially for the heterogeneous group of grade 2 carcinomas. PMID- 7788261 TI - Computerized analysis of transrectal ultrasonography images in the detection of prostate carcinoma. AB - OBJECTIVE: To report on the use of automated image analysis in the interpretation of transrectal ultrasonographic images of the prostate. PATIENTS AND METHODS: During transrectal ultrasonography, images were recorded from biopsies performed in 127 patients. Subsequently in the image, the puncture place was marked and analysed. Analysis of the images was performed with the Automated Urologic Diagnostic Expert (AUDEX) system, consisting of a personal computer connected to the ultrasound machine. From the images collected, parameters can be calculated for image classification. The parameters obtained with this procedure were correlated with the histological result. RESULTS: Evaluation showed a sensitivity of 84.8% and specificity of 87.5%. The positive and negative predictive values, to predict prostate carcinoma, were 84.8% and 87.5%, respectively. CONCLUSION: Automated image analysis can help in the diagnosis of prostate carcinoma. In patients with non-palpable lesions or with poorly visualized tumours, image analysis is superior to the standard current diagnostic techniques. PMID- 7788262 TI - Kinetic analysis of prostatic volume in patients with stage D prostatic cancer treated with LHRH analogues in relation to prognosis. AB - OBJECTIVE: To evaluate the clinical usefulness of the kinetic analysis of prostatic volume in the prognosis of patients with Stage D prostatic cancer treated using luteinizing hormone-releasing hormone (LHRH) analogues. PATIENTS AND METHODS: The reduction of prostatic volume was monitored in 12 patients with Stage D prostatic cancer using transrectal ultrasonography (TRUS) after treatment with LHRH analogues. Data obtained from the kinetic analysis of prostatic volume were compared with the prognosis. RESULTS: All the patients having a reduction time, tau (derived from the kinetic analysis of prostatic volume change with time), of less than 41 days had neither clinical progression within 15 months nor death caused by prostatic cancer during the 5-year follow-up, while the disease specific 5-year survival rate in patients having a tau of greater than 42 days was as low as 17%. The difference in both the progression and disease-specific survival between these groups was statistically significant (P < 0.05) despite the limited number of patients. In contrast, conventional prognostic parameters showed no significant predictability for prognosis with the exception of prostatic acid phosphatase, which correlated strongly with the occurrence of progression within 15 months. CONCLUSION: The kinetic analysis of the change of prostatic volume using TRUS shows promise in the prognosis of the patients with Stage D prostatic cancer. PMID- 7788263 TI - Nitric oxide and cyclic GMP formation following relaxant nerve stimulation in isolated human corpus cavernosum. AB - OBJECTIVE: To investigate further the role of the nitric oxide (NO)-cyclic GMP pathway as the mediator of relaxant neurotransmission in human corpus cavernosum and to establish whether impaired activity of this pathway contributes to the pathophysiology of impotence. PATIENTS AND METHODS: Samples of cavernosal tissue were obtained from 59 men undergoing penile operations. The controls comprised four men with penile carcinoma and 17 with Peyronie's disease. Of the impotent men, 35 had clinical evidence of penile vascular disease on pre-operative investigation, whilst three had non-vascular impotence. Each biopsy was divided into two strips which were then suspended under tension in organ bath chambers. The relaxant innervation of one strip of each pair was stimulated electrically whilst the other strip was left unstimulated. The formation of NO and cyclic GMP was calculated by comparing their respective tissue content in the stimulated and unstimulated strips. RESULTS: Overall, stimulation of the relaxant innervation produced significant increases in the tissue content of both NO and cyclic GMP. Incubation with an inhibitor of NO biosynthesis abolished the mechanical relaxant response and the formation of both NO and cyclic GMP. The magnitude of relaxant response and the formation of NO was diminished in tissue from men with vascular impotence compared to controls. The increase in cyclic GMP content was similar in both these groups. Relaxant response, NO formation and cyclic GMP formation in tissue from men with non-vascular impotence was similar to controls. CONCLUSIONS: This study provides further evidence that the NO-cyclic GMP pathway acts as the mediator of nerve-evoked smooth muscle relaxation in human corpus cavernosum. Diminished NO formation following relaxant nerve stimulation may account for impaired relaxant responses found in tissue from men with vascular impotence and may contribute to the cause of their erectile dysfunction. PMID- 7788264 TI - Laparoscopic varicocelectomy: technique and results. AB - OBJECTIVE: To determine the safety and efficacy of laparoscopic varicocelectomy in the treatment of symptomatic varicocele. PATIENTS AND METHODS: Indications for surgery were subfertility in 98 patients and pain in nine. All varicoceles were confirmed on Doppler ultrasound. Seventy-two per cent of the patients had left sided varicoceles and bilateral varicoceles were seen in 27%. A three-puncture technique was used with carbon dioxide insufflation. The spermatic vessels were individually identified and clips were used to ligate the veins. The spermatic artery was preserved in all cases. The operation was performed on a day surgery basis with an average operative time of 61.4 min (56.6 min for unilateral and 75.8 min for bilateral varicocelectomy). RESULTS: Morbidity was low, with pneumoscrotum in two patients and wound infection in two others. Sixty-one patients for whom pre- and post-operative seminal analyses were available showed improvement in sperm count and motility, with a concomitant fall in the percentage of abnormal sperm forms. CONCLUSION: Laparoscopic varicocelectomy is safe and effective, causing minimal discomfort and allowing patients an early return to activity. PMID- 7788265 TI - 'Congenital' hydronephrosis: limitations of diagnosis by fetal ultrasonography. AB - OBJECTIVE: To determine whether children presenting clinically with pelvi ureteric junction obstruction had fetal hydronephrosis. PATIENTS AND METHODS: Forty-three children, born during or after 1985, presented clinically with pelvi ureteric junction obstruction. Records of the maternal pregnancies were reviewed with reference to the findings of any fetal ultrasonography. RESULTS: In 25 patients fetal ultrasonography was performed at or beyond 30 weeks' gestation (mean 33.2). None had significant fetal hydronephrosis. CONCLUSION: Hydronephrosis due to pelvi-ureteric obstruction is not necessarily congenital and patients presenting clinically may differ inherently from those detected fetally. PMID- 7788268 TI - Delayed management of posterior urethral disruption in children. AB - OBJECTIVE: To review the results of delayed operative treatment of total disruption of the posterior urethra in children. PATIENTS AND METHODS: Twelve boys (3-12 years, mean 7.5) with a suprapubic catheter were referred after primary management in other hospitals. All but one had been involved in road traffic accidents. In addition to their urethral injury, they all had pelvic fractures and the majority also had other major associated injuries. Six to 14 months after injury, abdominoperineal transpubic urethroplasty was performed in 11 patients according to Turner-Warwick. In one case a perineal anastomotic urethroplasty was performed. RESULTS: After the operation, voiding cysto urethrography showed a wide anastomosis in all cases. After 3 to 45 months follow up, there were no strictures. Eight boys were continent, two were totally incontinent, two had stress incontinence and one nocturnal enuresis. All patients with confirmed erections after injury also had erections after their operation. CONCLUSION: Primary suprapubic cystostomy and delayed repair can be used successfully for the treatment of posterior urethral disruption in children. PMID- 7788267 TI - Endoscopic treatment of vesico-ureteric reflux and urinary incontinence: technical problems in the paediatric patient. AB - OBJECTIVE: Bovine collagen has been successfully used for the endoscopic treatment of urinary incontinence (UI) and vesico-ureteric reflux (VUR) in children for more than 8 years, although its long-term efficacy has sometimes been questioned. Its failure is generally ascribed either to technical difficulties or to instability of collagen at the site of the implant. To assess the efficacy of the procedure we evaluated the children treated at this hospital between 1990 and 1993. PATIENTS AND METHODS: A total of 156 children, aged 5 months to 13 years, were treated for VUR. Over the same period, 25 patients aged between 2 and 14 years (nine with neuropathic bladder and 16 with exstrophy epispadias complex who were still incontinent after bladder neck reconstruction) had periurethral or pericervical glutaraldehyde cross-linked bovine collagen injection for UI. Five more children with exstrophy-epispadias complex (aged 1-3 years) underwent periurethral collagen injection to stimulate bladder enhancement and allow subsequent bladder neck reconstruction. RESULTS: In children treated for VUR, a single injection proved successful in 72.2% of cases (127 ureters); a second collagen injection raised the success rate to 81%. Continence improved in all nine neuropathic bladders and in 10 of 16 children with exstrophy-epispadias complex treated for UI after bladder neck reconstruction. In four of the five exstrophy-epispadias complex patients who were treated to stimulate bladder enhancement, bladder capacity increased by 25%. CONCLUSIONS: Endoscopic treatment of VUR seems to be a valid alternative to open surgery, even though concerns remain about the long-term efficacy of collagen implantation. An important distinction should be made between early and late failure of the procedure. Early failure, which we define as persistence of reflux, is usually due to incorrect technique or technical difficulties. Late failure, or recurrence of reflux, which has previously been attributed to the biodegradability of collagen, seems to be due to the displacement of the injected collagen. Micturition itself or high bladder pressure (such as detrusor instability) could be responsible for the displacement of the injected collagen medially and distally, where it can no longer support the submucosal ureteric tunnel. In the treatment of urinary incontinence, both the implant technique and the choice of the site of injection seem to have a considerable effect on the results. In our experience, endoscopic collagen injection is effective in the treatment of both urinary incontinence and VUR in paediatric patients. Accurate selection of patients and technical adjustments and refinements are essential to obtain the best results. PMID- 7788266 TI - Natural filling cystometry in infants and children. AB - OBJECTIVE: To evaluate natural filling cystometry in infants and young children. PATIENTS AND METHODS: The study group comprised 37 infants and young children (mean age, 4.1 years) with various urological conditions. Suprapubic catheters were used in all patients with urethral sensation. Natural filling urodynamic (NFU) studies were performed using an ambulatory recorder and with an observer present throughout. For comparison, 17 of the 37 patients also had slow filling conventional cystometry (CMG). RESULTS: All NFU studies were successfully completed and the great majority of patients were unaffected by the investigation procedures. In comparison with conventional cystometry there were significant differences. For NFU, there was a lower bladder capacity (means, NFU 122 mL vs CMG 188 mL, P < 0.03); lower pressure rise on filling (means, NFU 5.7 cmH2O vs CMG 16.1 cmH2O, P < 0.001) and higher maximum detrusor pressures during micturition (means, NFU 130 cmH2O vs CMG 78 cmH2O, P < 0.01). Voiding efficiency was also slightly greater with NFU compared with CMG. Detrusor instability was recorded in five patients only during NFU and in two other patients only during CMG. CONCLUSION: A natural filling cystometry method which incorporates an unobtrusive recording system is likely to be superior to conventional CMG for assessing bladder function in infants and children. This is because (i) bladder function is investigated in near to natural conditions, (ii) the patients are mostly unaffected by the investigation procedures, (iii) there are significant differences between NFU and CMG in the measurements obtained, indicating that CMG may give false indices of bladder function. PMID- 7788269 TI - A drip-stand hook for the catheter bag to enable easy ambulation. PMID- 7788270 TI - Emergency laparoscopic repair of spontaneous and traumatic bladder rupture. PMID- 7788272 TI - Splenic-gonadal fusion: a case report of the discontinuous type. PMID- 7788271 TI - Giant hydronephrosis in a solitary pelvic kidney. PMID- 7788273 TI - Multicystic epididymes and seminal vesicles in a patient with polycystic kidney disease. PMID- 7788274 TI - Inverted papillary tumour of the ureter. PMID- 7788275 TI - Kaposi's sarcoma of the urethral meatus: management by urethral dilatation. PMID- 7788277 TI - Pseudo-haematuria caused by utero-urethral fistula from Mayer-Rokitansky-Kuster Hauser syndrome. PMID- 7788276 TI - Pelvic fibromatosis (desmoid)--treatment with steroids and tamoxifen. PMID- 7788278 TI - Renal plasmacytoma. PMID- 7788279 TI - The wider spectrum of megalourethra. PMID- 7788280 TI - Electron microscopic studies on intracellular phage development--history and perspectives. AB - This review is centered on the applications of thin sections to the study of intracellular precursors of bacteriophage heads. Results obtained with other preparation methods are included in so far as they are essential for the comprehension of the biological problems. This type of work was pioneered with phage T4, which contributed much to today's understanding of morphogenesis and form determination. The T4 story is rich in successes, but also in many fallacies. Due to its large size, T4 is obviously prone to preparation artefacts such as emptying, flattening and others. Many of these artefacts were first encountered in T4. Artefacts are mostly found in lysates, however, experience shows that they are not completely absent from thin sections. This can be explained by the fact that permeability changes induced by fixatives occur. The information gained from T4 was profitably used for the study of other phages. They are included in this review as far as electron microscopic studies played a major role in the elucidation of their morphogenetic pathways. Research on phage assembly pathways and form determination is a beautiful illustration for the power of the integrated approach which combines electron microscopy with biochemistry, genetics and biophysics. As a consequence, we did not restrict ourselves to the review of electron microscopic work but tried to integrate pertinent data which contribute to the understanding of the molecular mechanisms acting in determining the form of supramolecular structures. PMID- 7788281 TI - Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure. AB - The transmissible spongiform encephalopathies are a group of genetic and infectious disorders which are exemplified by scrapie in animals and Creutzfeldt Jakob disease in humans. The spongiform encephalopathies are characterized by symmetrical vacuolation of neurons and neuropil. Amyloid plaque formation similar to that found in Alzheimer's disease is conspicuous in many, but not all, of these diseases. The sub-cellular pathology features of the spongiform encephalopathies have been studied by conventional transmission electron microscopy, scanning electron microscopy, freeze fracture, negative staining and most recently by application of immunogold labelling methods. Although these studies have revealed many unusual structures, convincing virus-like particles have not been demonstrated. Considerable data, including important transgenic mouse studies, now suggest that a single cellular protein, designated prion protein, is necessary for infection. Ultrastructural immunogold studies have shown that prion protein is released from the surface of neurons and neurites, diffuses through the extracellular space around infected cells where it accumulates and finally becomes aggregated as amyloid fibrils. It is likely that the accumulation of prion protein within the extracellular space is instrumental in causing nerve cell dysfunction and, ultimately, neurological disease. PMID- 7788282 TI - The surgical approach to endocrine tumors of the pancreas. PMID- 7788284 TI - Multiple endocrine neoplasia type I. PMID- 7788283 TI - Recent advances in the treatment of metastatic pancreatic endocrine tumors. PMID- 7788285 TI - Diagnosis and treatment of pancreatic neuroendocrine tumors. PMID- 7788286 TI - Diagnosis and management of Zollinger-Ellison syndrome. PMID- 7788287 TI - Localization of pancreatic endocrine tumors. PMID- 7788288 TI - Annexins: a novel family of calcium- and membrane-binding proteins in search of a function. AB - Although the annexins have been extensively studied and much detailed structural information is available, their in vivo function has yet to be established. PMID- 7788289 TI - Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide. AB - The recent high-resolution solution structures of human and Escherichia coli thioredoxin in their oxidized and reduced states support a catalytic model of protein disulfide reduction involving binding of a target protein and nucleophilic attack by the active-site Cys32 thiolate to form a transition state mixed disulfide. PMID- 7788290 TI - Thioredoxin--a fold for all reasons. AB - The thioredoxin fold is a characteristic protein structural motif that has been found in five distinct classes of proteins that have the common property of interacting with cysteine-containing substrates. PMID- 7788291 TI - Hyperthermophiles: taking the heat and loving it. PMID- 7788292 TI - Crystal structure of the MS2 coat protein dimer: implications for RNA binding and virus assembly. AB - BACKGROUND: The coat protein in RNA bacteriophages binds and encapsidates viral RNA, and also acts as translational repressor of viral replicase by binding to an RNA hairpin in the RNA genome. Because of its dual function, the MS2 coat protein is an interesting candidate for structural studies of protein-RNA interactions and protein-protein interactions. In this study, unassembled MS2 coat protein dimers were selected to analyze repressor activity and virus assembly. RESULTS: The crystal structure of a mutant MS2 coat protein that is defective in viral assembly yet retains repressor activity has been determined at 2.0 A resolution. The unassembled dimer is stabilized by interdigitation of alpha-helices, and the formation of a 10-stranded antiparallel beta-sheet across the interface between monomers. The substitution of arginine for tryptophan at residue 82 results in the formation of two new inter-subunit hydrogen bonds that further stabilize the dimer. Residues that influence RNA recognition, identified by molecular genetics, were located across the beta-sheet. Two of these residues (Tyr85 and Asn87) are displaced in the unliganded dimer and are located in the same beta-strand as the Trp-->Arg mutation. CONCLUSIONS: When compared with the structure of the coat protein in the assembled virus, differences in orientation of residues 85 and 87 suggest conformational adjustment on binding RNA in the first step of viral assembly. The substitution at residue 82 may affect virus assembly by imposing conformational restriction on the loop that makes critical inter-subunit contacts in the capsid. PMID- 7788293 TI - Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG. AB - BACKGROUND: Streptococcal protein G comprises two or three domains that bind to the constant Fc region of most mammalian immunoglobulin Gs (IgGs). Protein G is functionally related to staphylococcal protein A, with which it shares neither sequence nor structural homology. RESULTS: To understand the competitive binding of these two proteins to the Fc region, the crystal structure of a single Ig binding domain of streptococcal protein G was determined at 3.5 A resolution in complex with the Fc fragment of human IgG and compared with the structures of protein A:Fc and protein G:Fab complexes. Protein G binds to the interface between the second and third heavy chain constant domains of Fc, which is roughly the same binding site used by protein A. Protein G comprises one alpha-helix packed onto a four-stranded beta-sheet. Residues from protein G that are involved in binding are situated within the C-terminal part of the alpha-helix, the N terminal part of the third beta-strand and the loop region connecting these two structural elements. The identified Fc-binding region of protein G agrees well with both biochemical and NMR spectroscopic data. However, the Fc-binding helices of protein G and protein A are not superimposable. CONCLUSIONS: Protein G and protein A have developed different strategies for binding to Fc. The protein G:Fc complex involves mainly charged and polar contacts, whereas protein A and Fc are held together through non-specific hydrophobic interactions and a few polar interactions. Several residues of Fc are involved in both the protein G:Fc and the protein A:Fc interaction, which explains the competitive binding of the two proteins. The apparent differences in their Fc-binding activities result from additional unique interactions. PMID- 7788294 TI - Structure of uncomplexed and linoleate-bound Candida cylindracea cholesterol esterase. AB - BACKGROUND: Candida cylindracea cholesterol esterase (CE) reversibly hydrolyzes cholesteryl linoleate and oleate. CE belongs to the same alpha/beta hydrolase superfamily as triacylglycerol acyl hydrolases and cholinesterases. Other members of the family that have been studied by X-ray crystallography include Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase. CE is homologous to C. rugosa lipase 1, a triacylglycerol acyl hydrolase, with which it shares 89% sequence identity. The present study explores the details of dimer formation of CE and the basis for its substrate specificity. RESULTS: The structures of uncomplexed and linoleate-bound CE determined at 1.9 A and 2.0 A resolution, respectively, reveal a dimeric association of monomers in which two active-site gorges face each other, shielding hydrophobic surfaces from the aqueous environment. The fatty-acid chain is buried in a deep hydrophobic pocket near the active site. The positioning of the cholesteryl moiety of the substrate is equivocal, but could be modeled in the hydrophobic core of the dimer interface. CONCLUSIONS: The monomer structure is the same in both the complexed and uncomplexed crystal forms. The dimers differ in the relative positions of the two monomers at the dimer interface. Of the 55 residues that are different in CE from those in C. rugosa lipase 1, 23 are located in the active site and at the dimer interface. The altered substrate specificity is a direct consequence of these substitutions. PMID- 7788295 TI - Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B. AB - BACKGROUND: Human thioredoxin is a 12 kDa cellular redox protein that plays a key role in maintaining the redox environment of the cell. It has recently been shown to be responsible for activating the DNA-binding properties of the cellular transcription factor, NF kappa B, by reducing a disulfide bond involving Cys62 of the p50 subunit. Using multidimensional heteronuclear-edited and hetero-nuclear filtered NMR spectroscopy, we have solved the solution structure of a complex of human thioredoxin and a 13-residue peptide extending from residues 56-68 of p50, representing a kinetically stable mixed disulfide intermediate along the reaction pathway. RESULTS: The NF kappa B peptide is located in a long boot-shaped cleft on the surface of human thioredoxin delineated by the active-site loop, helices alpha 2, alpha 3 and alpha 4, and strands beta 3 and beta 4. The peptide adopts a crescent-like conformation with a smooth 110 degrees bend centered around residue 60 which permits it to follow the path of the cleft. CONCLUSIONS: In addition to the intermolecular disulfide bridge between Cys32 of human thioredoxin and Cys62 of the peptide, the complex is stabilized by numerous hydrogen-bonding, electrostatic and hydrophobic interactions which involve residues 57-65 of the NF kappa B peptide and confer substrate specificity. These structural features permit one to suggest the specificity requirements for human thioredoxin catalyzed disulfide bond reduction of proteins. PMID- 7788297 TI - Appraisal of a glycopeptide cloaking strategy for a therapeutic oligopeptide: glycopeptide analogs of the renin inhibitor ditekiren. AB - Among the limitations to the practical therapeutic oligopeptide are low oral availability, indifferent aqueous solubility, and an astonishing efficient sequestration and biliary elimination by a multi-capacity liver transporter. Given the purposed use of N- and O- linked saccharides as functional appendages of eukaryotic peptides and proteins, a strategy of glycopeptide mimicry was examined for the oligopeptide renin inhibitor, ditekiren. The anticipation was that the saccharide would impart significant aqueous solubility, and might impact beneficially on the remaining two limitations. Execution of this approach was achieved by the removal of the (dimethylethoxy)carbonyl amino terminus of ditekiren, and its substitution by Boc-L-asparagine N-linked mono- and disaccharides. Potent hypotensive activity, as measured by a human renin-infused rat assay, is observed for virtually all of these structures (N-linked beta pyranose D-N-acetyglucosaminyl, D-glucosaminyl, D-N-acetylgalactosaminyl, D mannosyl, D-galactosyl, D-maltosyl, D-cellobiosyl, D-chitobiosyl, but not L fucosyl). The basis for this dramatic improvement (relative to ditekiren in the same assay) is the diversion of the peptide clearance from rapid liver biliary clearance to slower urinary clearance (Fisher, J. F.; Harrison, A. W.; Wilkinson, K. F.; Rush, B. R.; Ruwart, M. J. J. Med. Chem. 1991, 34, 3140). Guided by the human renin-infused rat hypertension assay, an evaluation of the linker saccharide pairing was made. Loss of hypotensive activity is observed upon substitution of the Boc-L-asn by Boc-D-asn, and by removal of the Boc amino terminus of the glycopeptide. Potent hypotensive activity is preserved by replacement of the Boc-L-asn linker by succinate, malate, tartrate, and adipate linkers. With the longer adipate spacer, attachment of the saccharide to the P-3 phenylalanine--with omission of the P-4 proline--retains activity. These data suggest value to the glycopeptide guise for preserving the in vivo activity, and for the beneficial manipulation of pharmacodynamics, of this renin inhibitory oligopeptide. This strategy may have general applicability. PMID- 7788298 TI - Potential radioprotective agents--IV. Schiff bases. AB - Twelve Schiff bases were prepared using salicylaldehyde, one with 5 chlorosalicylaldehyde, one with benzaldehyde, and a series of anilines substituted in the m- or p-positions. They were assayed for radioprotective activity in male, Swiss mice irradiated with a nearly lethal dose (950 cGy) of 6 mV photons produced by a linear accelerator, and were compared with the parent amines. Schiff base formation reduced toxicity of the parent amines; its effect on radioprotective activity was erratic, increasing activity in some cases, decreasing activity in others, and having no effect in still others. Radioprotective activity appears to be unrelated to a number of molecular descriptors. The highest radioprotection (100%) was observed for mixtures of p aminopropiophenone with its Schiff base, or with the Schiff base of 1-(p aminophenyl)-1-propanol (95%). PMID- 7788296 TI - The catalytic site of serine proteinases as a specific binding cavity for xenon. AB - BACKGROUND: Under moderate pressure, xenon can bind to proteins and form weak but specific interactions. Such protein-xenon complexes can be used as isomorphous derivatives for phase determination in X-ray crystallography. RESULTS: Investigation of the serine proteinase class of enzymes shows that the catalytic triad, the common hydrolytic motif of these enzymes, is a specific binding site for one xenon atom and shows high occupancy at pressures below 12 bar. Complexes of xenon with two different serine proteinases, elastase and collagenase, were analyzed and refined to 2.2 A and 2.5 A resolution, respectively. In both cases, a single xenon atom with a low temperature factor is located in the active site at identical positions. Weak interactions exist with several side chains of conserved amino acids at the active site. Xenon binding does not induce any major changes in the protein structure and, as a consequence, crystals of the xenon complexes are highly isomorphous with the native protein structures. Xenon is also found to bind to the active site of subtilisin Carlsberg, a bacterial serine proteinase, that also has a catalytic triad motif. CONCLUSIONS: As the region around the active site shows conserved structural homology in all serine proteinases, it is anticipated that xenon binding will prove to be a general feature of this class of proteins. PMID- 7788299 TI - A novel biotinylated heterobifunctional cross-linking reagent bearing an aromatic diazirine. AB - The synthesis of a p-[(3-trifluoromethyl)diazirine-3-yl]benzoic acid derivative is described as a new carbene generating heterobifunctional cross-linking reagent. The cross-linker carries a biotin moiety in order to make use of avidin biotin technology for specific manipulation of cross-linked components. To evaluate the ability of this reagent, the inter-subunit cross-linking of egg white avidin tetramer was investigated. As a typical application of avidin-biotin technology for cross-linking experiments, a chemiluminescent detection method was examined to identify photobiotinylated components. A cross-linked dimeric product with an apparent molecular mass of 38 kDa was clearly visualized by the combined use of a horseradish peroxidase-streptavidin conjugate and a luminol-based chemiluminescent system. PMID- 7788300 TI - Synthesis, absolute configuration, conformational analysis and binding affinity properties of enantiomeric forms of DAU 5750, a novel M1-M3 muscarinic receptor antagonist. AB - Both the enantiomeric forms of DAU 5750, a novel muscarinic receptor antagonist, have been synthesized in order to assess the relevance of configurational/conformational features for high affinity binding to muscarinic receptor subtypes. The attribution of absolute stereochemistry and conformational analysis by means of molecular modelling and NMR techniques are also reported. PMID- 7788302 TI - Synthesis of novel water-soluble 7-(aminoacylhydrazono)-formyl camptothecins with potent inhibition of DNA topoisomerase I. AB - Eighteen new water-soluble 7-(aminoacylhydrazono)-formyl camptothecins were synthesized and evaluated for their ability to cause protein-linked DNA breaks and to inhibit topoisomerase I activity. Compared with camptothecin, five of the compounds were as potent or more potent in these tw assays but were less toxic in several cancer cell lines. The results suggest that the 7 position in the B ring is a suitable location for introducing a polar moiety into camptothecin producing analogues with enhanced topoisomerase I inhibiting activity. PMID- 7788301 TI - Iron(II)/reductant(DH2)-induced activation of dioxygen for the hydroxylation and ketonization of hydrocarbons; mimics for the cytochrome P-450 hydroxylase/reductase system. AB - Several metal complexes [(FeII(DPAH)2 (DPAH2 = 2,6-dicarboxyl pyridine), FeII(PA)2 (PAH = picolinic acid), FeII(bpy)2(2+), FeII(OPPh3)4(2+), (Cl8TPP)FeIIIX (X = Cl, OH, SCH2Ph) [Cl8TPP = tetrakis (2,6 dichlorophenyl)porphyrin], (TPP) FeIIICl (TPP = tetraphenylporphyrin), and CuI(tpy)2+ (typ = 2,2'-6,2"-terpyridine)] in combination with one of several reductants [DH2; PhNHNHPh (mimic of dihydroflavin), PhNHNH2, ascorbic acid (H2asc), and PhCH2SH (model ligand for cysteine residue)] catalytically activate O2 (1 atm) for the hydroxylation of saturated hydrocarbons (e.g. c-C6H12-->c C6H11OH). This chemistry closely parallels that of cytochrome P-450 proteins, and both appear to involve a Fenton-like reactive intermediate), [LxFeOOH(DH)]. With cyclohexane as the substrate the dominant product is its ketone (as well as significant amounts of its hydroperoxide). 1,4-Cyclohexadiene (with two double allylic carbon centers) undergoes dehydrogenation to give benzene, but also yields substantial amounts of phenol via ketonization of an allylic carbon. The 1:1 FeII(bpy)2(2+)/(PhNHNH2 or H2asc), FeII(PA)2/H2asc, and (Cl8TPP)FeIIICl/PhNHNH2 combinations initiate the autoxidation of 1,4 cyclohexadiene with turnover numbers (moles of product per mole of reductant) from 71 to 26, respectively (alpha-tocophenol reduces the turnover numbers by 20 80%). With respect to aerobic biology, the present results indicate that dysfunctional transition metals (degradation products of metalloproteins) in combination with biological reductants activate O2 for reaction with organic substrates. The level of activation is similar to that for Fenton reagents and cytochrome P-450 hydroxylases. Hence, dysfunctional transition metals, reductants, and O2 are a hazardous combination within a biological matrix. PMID- 7788304 TI - Phage display of catalytically active staphylococcal nuclease. AB - Staphylococcal nuclease (SNase), a 14 kD enzyme that catalyzes the hydrolysis of single- and double-stranded nucleic acid, was fused to the N-terminus of the gene III (pIII) protein of filamentous phage fdtet. The SNase-pIII protein is infective and the catalyzes DNA hydrolysis, demonstrating that functional SNase can be displayed on the phage surface. PMID- 7788305 TI - Structurally designed novel furogamma lactams as inhibitors for bacterial propagations. AB - Some novel furogamma lactams have been synthesised by one step condensation of arylaminomalonates with substituted furyl acryloyl chlorides. The annulation of substituted monocyclic gammalactams followed by cyclization produced novel tricyclic furogamma lactams. Some of these furogammalactams are found to exhibit Gram-positive and Gram-negative antibacterial activity at very high concentrations. PMID- 7788303 TI - Antiproliferative actions of 7-substituted 1,3-dihydroxyacridones; possible involvement of DNA topoisomerase II and protein kinase C as biochemical targets. AB - 7-Chloro-1,3-dihydroxyacridone (1) reversibly inhibited growth of KB and vero cell lines with IC50's of 35 and 40 microM, respectively, and a topoisomerase II mediated multidrug resistant KB sub-clone was found to be about three-fold more susceptible to 1. In contrast, two cell lines of lymphoid origin were killed following treatments with 60 microM and at higher concentrations of 1. KB cell growth inhibition correlated with a rapid, reversible suppression of thymidine incorporation. Uridine but not leucine incorporation was also rapidly suppressed. The in vitro activities of DNA topoisomerase II and novel protein kinase C subtype delta were inhibited at effective concentrations in tissue-culture, but 1 did not stimulate intracellular protein-associated DNA breaks nor interfere initially with topoisomerase II-mediated DNA cleavage in KB cells. In addition to antiproliferative effects against cells, the compound was weakly virustatic for herpes simplex virus type I with an IC50 of 8 microM. Limited studies comparing three 1-congeners and citpressine-I, an acridone alkaloid with reported antiherpes activity, demonstrated that 7-substituted 1,3-dihydroxyacridones are novel antiproliferative agents which share similar biological and biochemical properties. PMID- 7788306 TI - Structure-activity studies leading to potent chloride channel blockers: 5e-tert Butyl-2-[4-(substituted-ethynyl)phenyl]-1,3-dithianes. AB - 5e-tert-Butyl-2e-[4-(substituted-ethynyl)phenyl]-1,3-dithianes+ ++ with selected functional groups (R) on the ethynyl moiety are potent blockers of the GABA-gated chloride channel measured as inhibitor concentration (IC50) for 4-n-[3H]propyl-1 (4-ethynylphenyl)-2,6,7- trioxabicyclo[2.2.2]octane binding to bovine brain membranes. The terminal R substituents were introduced by coupling 5e-tert-butyl 2e-(4-iodophenyl)-1,3-dithiane with HC identical to CR or 5e-tert-butyl-2e(4 ethynylphenyl)-1,3-dithiane with XR. The potency of the parent compound (R = H) with an IC50 of 21 nM is equaled or exceeded by up to 7-fold (i.e. IC50 = 3-21 nM) by several carboxylic acids [R = (CH2)nCO2H (n = 0-3), (CH2)nOCH2CO2H (n = 1 3), and CH2SCH2CO2H] and their esters and two phosphonic acids (CH2CH2PO3H2 and CH2OCH2PO3H2) but not their esters. These carboxylic and phosphonic acids (and their salts) include the most potent water-soluble chloride channel blockers known. Conversion to the monosulfones increases the activity of the R = H and CH2OH analogs by 1.2- to 3-fold but decreases that of the R = CH2CH2CO2R' (R' = H or CH3) derivatives by 3- to 13-fold. Quantitative structure-activity analyses for 44 2-[4-(substituted-ethynyl)phenyl]-dithianes suggests that the principal feature of the R substituent for high activity is its polarizable volume modeled as molecular refractivity, i.e. this substituent is not a well-defined pharmacophore and undergoes a structurally non-specific interaction with the receptor. These observations lay the background for preparing candidate affinity probes. PMID- 7788308 TI - Bilateral spontaneous patellar tendon rupture in the absence of concomitant systemic disease or steroid use. PMID- 7788307 TI - On implants and tumors. PMID- 7788309 TI - On recycling in the operating room. PMID- 7788310 TI - Wrist arthroscopy. AB - Miniaturization of arthroscopic equipment has allowed wrist arthroscopy to emerge as a powerful surgical tool in orthopedic surgery. The magnified view of the arthroscope has provided a new understanding of carpal anatomy and disease. Arthroscopy improves surgeons' ability to diagnose wrist disorders and enables them to perform operative procedures with less morbidity than would occur in open procedures. PMID- 7788311 TI - Carcinogenicity and metallic implants. AB - The literature related to the carcinogenetic potential of metallic implants was reviewed. There were 20 cases described in which tumors were identified in proximity to metallic implants. These cases occurred over a 34-year period. Investigators have identified a 70% increased incidence of lymphomas and hematopoietic tumors over that in the general population in patients who had received total hip arthroplasties. Carcinogenicity theories include the potential direct toxicity of materials, the effects of surface properties, the electromotive potential created by dissimilar metals in contact, the immunologic response to implants, and finally, the sustained presence of low-grade infection. Corrosion is a well-documented phenomenon and occurs with any type of metal. The rate of formation of corrosion products and their toxicity varies with the implant composition. Toxic effects of metals, such as malignant potential and other adverse effects, have been demonstrated in animal models. The published information on this controversial and very poignant issue of metallic carcinogenesis is useful for all orthopedic surgeons. PMID- 7788312 TI - In search of the perfect ACL brace. AB - Following my own acute anterior cruciate ligament (ACL) tear and reconstruction, I embarked on a subjective evaluation of ACL functional braces voluntarily supplied by vendors. Both custom and off-the-shelf braces were evaluated during daily activities and running. Scored subjectively on an ascending scale of 1 to 3 were Comfort (including freedom from slippage, abrasions, and pressure phenomena), Convenience (ease of application), Control (perceived resistance to anterior tibial translation), and Cosmesis (appearance, profile). On this rating scale, 1 represents below average, 2 is average, and 3 is above average. The Comfort score was doubled, as this feature determined whether the brace would be worn. The individual scores were then totaled for an overall rating. To avoid bias, I did all trials prior to reviewing the literature. Scores for custom braces were: Townsend, 14; Omni Scientific Elite, 11; Innovation Sports C.Ti.2, 10; 3M Lenox Hill Spectralite, 9; Orthotech Performer, 9; DonJoy Defiance, 9; and Sutter Talon, 9. Scores for OTS braces were: DonJoy Goldpoint, 13; Orthotech Controller, 11; Bledsoe Force III Light, 11; 3M Lenox Hill OTS, 10; Innovation Sports MVP, 8; Bledsoe Force II, 8; Bledsoe Force II Light, 8; Omni Scientific Spectrum, 7; Townsend OTS, 7; and DonJoy Playmaker, 6. This study does not validate the requirement for a functional orthosis following ACL reconstruction, but if one is desired, I prefer the custom Townsend and the OTS DonJoy Goldpoint. Two other higher scoring OTS braces also proved satisfactory (OTS Orthotech Controller and OTS Bledsoe Force III Light). To accommodate the majority of patients, orthopedic surgeons may need to provide a variety of OTS braces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788313 TI - Femoral varus derotational osteotomy in cerebral palsy. AB - The records concerning 64 hips in 36 cerebral palsy patients treated with varus derotational osteotomy (VDO) alone (2 hips), VDO with muscle releases (adductors, iliopsoas, hamstrings; 46 hips), and VDO, soft-tissue release, and innominate bone osteotomy (16 hips) were reviewed. There were 23 quadriplegic and 13 diplegic patients. Average age at surgery was 7 years. Average follow-up period was 3.8 years. All hips that had VDO, soft-tissue release, and innominate osteotomy were stable at follow-up. Nine hips of the 44 treated with VDO and muscle release alone dislocated, and required second osteotomies. PMID- 7788314 TI - Clinical significance of leg-length inequality after total hip arthroplasty. AB - Sixty-eight patients were interviewed and examined after total hip arthroplasty (THA) to determine the clinical consequences (patient satisfaction, shoe lift use, gait abnormalities, etc) of leg-length inequality. No patient met clinical or radiographic criteria for revision THA. Minimum follow-up was 2 years, and average follow-up was 6.6 years (range, 2 to 20.5 years). A questionnaire, with specific questions about leg-length inequality, was completed by each patient. Leg-length inequality was determined by orthoroentgenography and compared with clinical measurements of leg length. The average inequality in this series of patients was 9.7 mm. A significant number (32%) of patients were aware of this inequality; the average leg-length inequality in this group was 14.9 mm. More than half of these patients were disturbed by the inequality. The magnitude of leg-length inequality closely correlated with awareness of the inequality, abnormal gait, use of ambulatory assistive devices, the need for a shoe lift, prior leg-length inequality, and revision THA. Clinical measures of leg-length inequality correlated poorly with values determined orthoroentgenographically. The high rate of dissatisfaction among patients with a leg-length inequality and the untoward results associated with this inequality indicate that surgeons performing THA should familiarize themselves with a reliable method for equalizing leg lengths intraoperatively. PMID- 7788315 TI - Spontaneous rupture of the tibialis anterior tendon. AB - Spontaneous rupture of the tibialis anterior tendon is an uncommon occurrence that most often affects men in their fifth to seventh decades. These ruptures occur through abnormal tendons, but may cause little disability. Early repair does seem to improve the likelihood of a good result, however. The following is a case report, and the English literature is reviewed. PMID- 7788316 TI - A technique for cementing of the patellar component in total knee arthroplasty. AB - A technique is described for cementing of the patellar component in total knee arthroplasty that involves pressurization of cement into the patellar-component lug holes, which are drilled in the bone prior to cementing the component. A radiographic comparison of cement penetration with this method versus that obtained by using conventional techniques is illustrated. PMID- 7788317 TI - A 7-year-old girl with a growth disturbance in the extremities. AB - The following case describes the roentgenographic and clinical findings of a condition of interest to the orthopedic surgeon. Initial history, physical findings, and roentgenographic examinations are found on this page. The final clinical and roentgenographic differential diagnosis can be found on the pages that follow. PMID- 7788318 TI - Are classification criteria for spondylarthropathy useful as diagnostic criteria? AB - The authors used data from a study conducted under the auspices of the Societe Francaise de Rhumatologie to evaluate the sensitivity and specificity of the individual items of two sets of criteria for spondylarthropathy. The study included 124 patients with spondylarthropathy and 1,964 controls. They found that the spondylarthropathy criteria with the highest sensitivities and specificities were useful not only for classifying patients but also for assisting in the diagnosis of spondylarthropathy. PMID- 7788319 TI - Polyarthritis in HTLV-1-infected patients. A review of 17 cases. AB - A retrospective study was conducted in Martinique to identify patients with polyarthritis and positive serologic tests for the human T-cell lymphotropic virus Type I (HTLV-1). Patients with metabolic or bacterial causes of polyarthritis were excluded. We found 17 cases of HTLV-1-positive polyarthritis (6.7% of the total of polyarthritis patients followed in our department); there were 14 females and three males, and all the patients were West-Indian blacks. Mean age at diagnosis was 50 years. Five patients also had tropical spastic paraparesis. The polyarthritis was the inaugural manifestation of T-cell leukemia in one patient. Four patients had received blood transfusions. Fever, myalgia, and/or skin lesions were present at onset of the polyarthritis in seven cases. All 17 patients had peripheral, bilateral, symmetric polyarthritis; the most commonly involved sites were the hands (17/17) and knees (14/17). Three patients had rheumatoid factor and five had antinuclear antibody. Ten patients met at least four American Rheumatism Association criteria for rheumatoid arthritis; they accounted for 6.7% (10/150) of all polyarthritis patients managed in the same hospital department during the same period. We compared these ten patients with 20 HTLV-1-negative rheumatoid arthritis patients matched on gender, ethnic origin, and disease duration. There were no significant differences between the two groups for any of the parameters studied. PMID- 7788320 TI - Cervical epidural infection. Four case-reports. AB - The authors report four cases of cervical epidural infection, in two females (aged 58 and 82 years) and two males (aged 41 and 51 years). Risk factors were noninsulindependent diabetes mellitus in one patient and multiple myeloma treated by chemotherapy in another. Duration of cervical pain at evaluation was five to 15 days. Three patients had a fever and a neurologic deficit: one had brachial diplegia; the myeloma patient developed brachial diplegia after a lumbar puncture and the diabetic patient developed quadriplegia with respiratory disorders also after a lumbar puncture. Cerebrospinal fluid studies showed elevated protein levels with approximately 20 cells per mm3 and no pathogens in smears or cultures. Roentgenograms were normal at admission. The diagnosis was established by myelography (n = 2) and/or computed tomography (n = 2) and/or magnetic resonance imaging (n = 2). The infected area was anterior in three cases and posterolateral in one. Two to seven vertebral levels were affected. A Staphylococcus aureus was recovered from the blood cultures in all four cases and from a local specimen in one of the two patients who had a laminectomy. Of the two patients who did not have surgery, one had a normal neurologic evaluation and the other was an elderly patient with myeloma. In both, antimicrobial and corticosteroid therapy ensured complete resolution of the infection, and the myeloma patient recovered normal neurologic function. Residual neurologic loss was seen in one of the two surgically-treated patients. Two patients developed discitis. PMID- 7788321 TI - Calcitonin and osteoporosis. Fact and fiction. PMID- 7788322 TI - Rehabilitation of low back pain patients. A review. AB - Numerous methods have been developed for the rehabilitation of low back pain patients, including spinal flexion and extension exercises, lumbar spine locking in an intermediate position, enhancement of spinal and pelvic proprioceptive sensibility, swimming pool therapy, back schools, and functional restoration. Each seeks to achieve a goal assumed to be central to the prevention of a first or recurrent episode of low back pain. Goals include short-term pain relief, an improved ability to achieve self-sedation, abdominal and lumbar muscle strengthening, increased hip and lumbar spine mobility, improved lumbar and pelvic proprioceptive sensibility, intervertebral joint stabilization, lumbar posture modification and improved general fitness. Less than 30 studies meeting widely accepted validity and applicability criteria for therapeutic trials have addressed the clinical efficacy of rehabilitation in low back pain patients. Most studies of the back school approach have found no benefit. Spinal flexion and extension exercise programs have yielded short-lived improvements, with no differences across methods. There is evidence that functional restoration programs based on graded activity may provide long-term benefits including better social and occupational outcomes. We have evaluated the physical therapy methods most commonly taught to and used by physical therapists in France. PMID- 7788323 TI - Monostotic Paget's disease involving the calcaneus. Diagnostic and therapeutic problems. Two case-reports. AB - The authors report the cases of two patients who had chronic incapacitating heel pain unresponsive to standard therapy. They were both found to have Paget's disease of the calcaneus. The diagnosis was difficult because the typical roentgenological changes required time to develop and because no other sites were involved. Local corticosteroid injections, elimination of weight-bearing, and standard analgesic therapy were ineffective. Bisphosphonate therapy (pamidronate) given as intravenous infusions ensured prompt lasting pain relief, making ambulation possible. PMID- 7788325 TI - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) as the first manifestation of periarteritis nodosa. Report of a case. PMID- 7788324 TI - Longitudinal insufficiency fractures of the femoral shaft. AB - Most insufficiency fractures of the femur are transverse fractures of the femoral neck. We report two 77-year-old female patients with longitudinal fractures of the femoral shaft; one had a vertical fracture line in the proximal part of the shaft and the other a spiroid line in the middle third of the shaft. Both patients experienced apparently spontaneous onset of incapacitating mechanical pain in the hip or thigh; duration of the pain at evaluation was ten days in one case and six months in the other. Potential risk factors were osteoarthritis of the hip and the presence of metalwork in the knee. Increased radionuclide activity at the fracture site was seen on the bone scans. In one patient, roentgenographic and computed tomography findings were normal and the diagnosis was established by magnetic resonance imaging. In the other, the fracture line was seen clearly on computed tomography sections. Longitudinal fractures often escape diagnosis initially because roentgenographic changes are delayed. Hyperactivity on the bone scan is suggestive but sometimes so extensive as to mislead the diagnosis. The callus and, less frequently, the fracture line are sometimes seen on computed tomography sections. The role of magnetic resonance imaging remains to be determined. PMID- 7788326 TI - Lumbar intraspinal juxtaarticular cyst. Report of a case with MRI findings. PMID- 7788327 TI - Post traumatic seronegative polyarthritis. PMID- 7788328 TI - Disseminated leiomyosarcoma of the bone with progesterone receptors. PMID- 7788329 TI - Sjogren's syndrome revisited. PMID- 7788330 TI - Chondrometry. Quantitative evaluation of joint space width and rate of joint space loss in osteoarthritis of the hip. PMID- 7788331 TI - Parathyroid hormone related-peptide: how much do we know after seven years? PMID- 7788332 TI - HLA-DPB1*0201 is associated with particular clinical features of rheumatoid arthritis. AB - AIMS: to determine the effect of HLA-DPB1 status on rheumatoid arthritis (RA) susceptibility and disease expression. METHODS: HLA-DPB1 alleles were identified in 158 RA patients and 106 controls using PCR-sequence specific oligonucleotide probing. HLA-DPB1 allele frequencies were compared between patient and control groups and the strength of associations assessed using odds ratios and with 95% confidence intervals (CI). Associations observed in the total RA group were confirmed using a relative predispositional effect (RPE) analysis. RESULTS: an association between DPB1*0201 and RA was observed (OR 1.8, 95% CI 1.0-3.4). By contrast, negative associations were found with DPB1*0301 (OR 0.5, 95% CI 0.3 1.0) and DPB1*1101 (OR 0.06, 95% CI 0.001-0.5). These associations were confirmed using RPE analysis. On further analysis the increase in DPB1*0201 and decrease in DPB1*0301 frequencies in RA was found to be independent of DR4 status. The association of DPB1*0201 with RA appears to be most pronounced in male patients (OR 3.3, 95% CI 1.3-8.3), seronegative patients (OR 2.6, 95% CI 0.9-7.3) those with non-erosive disease (OR 2.6, 95% CI 0.9-7.3) or in patients with high titre antinuclear antibodies (OR 2.4, 95% CI 0.8-7.1). CONCLUSIONS: HLA-DPB1 alleles may be associated with the pattern of disease expression in certain RA patients and in some cases confer protection against disease. PMID- 7788333 TI - Sensitivity to change of various roentgenological severity scoring systems for osteoarthritis of the hip. AB - RATIONALE: joint space assessment on roentgenograms is considered reliable for evaluating the anatomic severity of hip osteoarthritis. Methods for measuring this parameter include the scoring system developed by Kellgren and Lawrence, joint space width measurement, and joint space surface area measurement after digitalization of roentgenograms. OBJECTIVE: to compare the sensitivity to change of the three above-listed methods. PATIENTS AND METHODS: the study included patients with hip osteoarthritis meeting ACR criteria for whom two roentgenograms showing evidence of hip osteoarthritis taken 10 to 15 months apart were available. Roentgenograms were read by a single investigator who was unaware of the chronological order of films. Sensitivity to change of the three measurement techniques was determined by calculating standardized response mean (mean change/standard deviation of change). RESULTS: the study evaluated 34 hips (68 roentgenograms) in 22 patients (12 females and ten males, mean age 63 +/- 10 years) with osteoarthritis of one (n = 10) or both (n = 12) hips. Standardized response mean were 0.37, 0.33, and 0.16 for joint space width, joint space surface area, and the Kellgren-Lawrence score, respectively. CONCLUSION: this study suggests that joint space width or surface area may be more sensitive than the Kellgren-Lawrence score for monitoring the course of hip osteoarthritis. PMID- 7788334 TI - Adult-onset idiopathic phosphate diabetes. I. Chronic pseudoinflammatory back pain and osteopenia. AB - STUDY OBJECTIVE: to investigate clinical, laboratory test, and bone mineral density abnormalities in 19 adults with phosphate diabetes of unknown etiology diagnosed in a rheumatology department on the basis of a maximal rate for tubular reabsorption of phosphate (TmPO4/GFR) of 0.77 or less. RESULTS: there were 14 males and five females with a mean age of 36.7 years (range 20 to 68 years) at symptom onset and 43.9 years (24-70) at diagnosis. Seventeen patients (90%) had back pain and 13 (68%) had nerve root pain. The pain was nocturnal only or both nocturnal and diurnal in 14 cases (74%). Other manifestations were fatigue (n = 7, 37%), myalgia (n = 6, 32%), fracture (n = 6, 32%), renal colic (n = 4, 21%), and pseudodepression (n = 10, 53%). Laboratory test abnormalities were as follows: serum phosphate, 0.72 mmol/L (0.58-0.89); rate for tubular reabsorption of phosphate, 74% (54-84%); maximal rate for tubular reabsorption of phosphate, 0.58 (0.4-0.76); urinary calcium/urinary creatinine > 0.48 in nine patients (47%); and fractional potassium excretion > 20% in seven patients (37%). Normal values were found for serum levels of Ca++, Na++, Mg++, creatinine, cortisol, T3, T4, TSH, 25(OH)D3, and 1,25(OH)2 D3. Tests for glycosuria and amino aciduria were negative. Bone mineral density measurements showed z-scores of -2.13 (+0.9 to 4.25) at L2-L4, and -1.34 (+1.5 to -3.2) at the femoral neck. Bone histology showed osteoporosis with a mild increase in osteoid deposition. CONCLUSIONS: idiopathic adult-onset phosphate diabetes manifests as chronic back pain and nerve root pain, sometimes with fatigue and depression. Bone mineral density values are decreased and histology shows osteopenia. Differential diagnoses include spondyloarthropathy, disk disease, fibromyalgia, and depression. Determination of the maximal rate for tubular reabsorption of phosphate is the only means of establishing the diagnosis. PMID- 7788335 TI - Adult-onset idiopathic phosphate diabetes. II. Time-course of clinical, laboratory test, and bone mineral density abnormalities under combined phosphate and calcitriol therapy. AB - STUDY OBJECTIVE: to investigate the time-course of clinical, laboratory test, and bone mineral density abnormalities in patients with mild phosphate diabetes treated for at least one year with calcitriol, 0.5 to 1.5 micrograms, and oral phosphate, 788 to 2300 mg per day, in three divided doses. PATIENTS AND METHODS: we studied eight patients with mild phosphate diabetes defined as a rate for tubular reabsorption of phosphate of less than 18% with a maximal rate for tubular reabsorption of phosphate (Tm) of less than 0.77 in the absence of any detectable cause of secondary tubular disease. Treatment efficacy was evaluated on the basis of pain severity, pain-related functional disability, serum phosphate and calcium levels, maximal rate for tubular reabsorption of phosphate, and dual-photon absorptiometry-measured bone mineral density. RESULTS: three patients experienced complete relief of pain and fatigue and were able to resume their normal activities. Partial relief was seen in two other patients. The three remaining patients had no response to treatment. Renal colic occurred in one patient. None of the patients developed hypercalcemia. PMID- 7788336 TI - Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia. AB - Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788337 TI - Bone tissue in rheumatoid arthritis (1). Bone mineral density and fracture risk. AB - Rheumatoid arthritis is associated with locoregional decalcification, which can be clearly demonstrated at the distal radius using single-photon absorptiometry. Bone loss at this site is probably due to the predominant involvement of the hands and wrists during rheumatoid arthritis. Estimates of the frequency of generalized bone loss have varied with the measurement technique used and the study design. Studies using dual-photon absorptiometry with a radioactive source have yielded conflicting data. The most recent studies of bone mineral density used dual energy X-ray absorptiometry, which is currently the best method in terms of reproducibility and precision; results suggested bone loss in the proximal femur, whereas lumbar spine measurements were usually normal or very slightly decreased. Findings from the few longitudinal studies are discordant; this may be ascribable to differences in bone mass measurement techniques, study population characteristics, and follow-up duration. Whereas bone loss was not demonstrated in the earliest longitudinal studies, recent investigations suggested that bone mineral density was decreased in rheumatoid arthritis patients as compared with controls. Corticosteroid therapy, even in daily dosages of less than 10 mg/d prednisone-equivalent, was associated with an approximately 10% decrease in bone mass after six months, in both cross-sectional and longitudinal studies. Rheumatoid arthritis patients had a two-fold increase in fracture risk, independently from their bone mass. Factors associated with higher fracture risks were corticosteroid therapy, physical inactivity, and female gender. PMID- 7788338 TI - Bone tissue in rheumatoid arthritis (2). Pathophysiologic data, pathologic findings, and therapeutic implications. AB - The occurrence of bone decalcification during rheumatoid arthritis is well documented, despite discrepancies among published data. The most recent studies support a decrease in bone mass, especially at the proximal femur, although estimations of the extent of bone loss ascribable to rheumatoid arthritis vary. The fracture risk is increased by approximately 100% in rheumatoid arthritis patients. Bone mass is negatively correlated with functional impairment, joint motion restriction and disease activity as assessed by laboratory tests for inflammation. Increased physical activity can reduce bone loss. Markers for bone formation (osteocalcin, procollagen type I carboxy-terminal propeptide) are normal or decreased, whereas markers for bone resorption (hydroxyproline, pyridinoline, and deoxypyridinoline) are elevated. This decoupling of bone formation and resorption may be responsible for bone loss. Although estrogen therapy can keep in check menopause-related bone loss, earlier findings suggesting that estrogens may have beneficial effects on the joint disease itself have been disproven. The value of preventive bisphosphonate therapy is currently under debate. PMID- 7788339 TI - Intrasacral meningocele. Report of a case. AB - A case of intrasacral meningocele with low back pain and sciatica as the presenting manifestations in a 47-year-old male is reported. Magnetic resonance imaging established the diagnosis. Surgical treatment was successful. PMID- 7788340 TI - Aspergillus arthritis of the shoulder in a renal transplant recipient. Failure of itraconazole therapy. AB - We report a case of Aspergillus arthritis of the shoulder in a renal transplant recipient. Cultures of three joint fluid specimens grew Aspergillus fumigatus. Itraconazole as sole treatment resulted in initial clinical and roentgenographic improvements but failed to prevent deterioration in joint function. A relapse with fatal neurologic involvement occurred. Immune deficiency-inducing risk factors for aspergillosis include neutropenia and corticosteroid therapy. Previously published cases of Aspergillus arthritis of limb joints are reviewed. The advantages and limitations of itraconazole as single drug therapy are outlined. PMID- 7788342 TI - Rheumatic manifestations of pseudomembranous colitis. PMID- 7788341 TI - Calcium pyrophosphate dihydrate crystal deposition disease in the elderly. AB - Calcium pyrophosphate dihydrate deposition disease can mimic a large number of joint diseases. We report on three patients with predominantly systemic symptoms. Diagnostic pitfalls and treatment delays in these patients are discussed. Once the diagnosis is considered, confirmation is readily obtained by examination of the joint fluid and treatment promptly relieves symptoms. PMID- 7788343 TI - Reactive arthritis ascribed to Chlamydia pneumoniae. Report of a case. PMID- 7788344 TI - Hypothesis on the nature of comprehension deficit in a patient with transcortical mixed aphasia with preserved naming. AB - Patients with poor comprehension and preserved naming have been occasionally described. Such patients, who are affected by transcortical aphasia, have been taken as evidence of the possibility of naming an object while bypassing the semantic system. We describe a patient affected with mixed transcortical aphasia who presented a clear dissociation between ability in naming and difficulties in performing word-picture matching tasks. The pattern is explained by the existence of covert compulsory automatic naming that interferes with less automatic procedures involved in word-picture matching. In fact, when we tried to oppose automatic naming by using, in word-picture matching tasks, pictures difficult to name, the comprehension improved. This finding excludes a semantic deficit at the basis of poor comprehension of our patient. We suggest that the dissociation between naming and comprehension could be an expression of a computational limitation within the processes involved in word-picture matching, due to the competition for limited processing resources by automatically activated hyperactive naming. PMID- 7788345 TI - Decline in homophone spelling associated with loss of semantic influence on spelling in Alzheimer's disease. AB - The homophone spellings of 20 subjects with Alzheimer's disease (AD) and mild dementia were compared to those of matched normal controls. Both groups were tested once (Time 1) and then again 9 months to 1 year later (Time 2). At Time 1, AD subjects misspelled more homophones than the control group and the discrepancy between the two groups' performances significantly increased by Time 2. Two types of errors were tabulated: homophone confusions (i.e. an inappropriate yet correctly spelled homophone given the context, such as spelling doe, given the context "bake the bread dough") and other spelling errors (e.g. doue, dogh). The relationship between homophone confusions and confrontation naming increased from Time 1 to Time 2. In contrast, the relationship between the number of spelling errors (that were not homophone confusions) and confrontation naming performance was not significant at Time 2. One subgroup of 3 subjects showed an increase in homophone confusions and confrontational naming errors and not more spelling errors. Another subgroup of 4 subjects showed neither an increase in homophone confusions nor in confrontational naming errors, but did show an increase in spelling errors. Based on these results, we suggest that homophone confusions are primarily due to impairment of semantic access to a functional orthographic output lexicon. Other spelling errors may reflect post-linguistic spelling deficits without a significant change in the use of semantic input for spelling homophones. PMID- 7788346 TI - Syntactic processing in agrammatic aphasia by speakers of a Slavic language. AB - It is widely believed that agrammatic aphasics have lost the ability to assign complete syntactic representations. This view stems from indications that agrammatics often fail to comprehend complex syntactic structures, as for example, some types of relative clauses. The present study presents an alternative account. Comprehension by Serbo-Croatian-speaking agrammatic aphasics was tested on four types of relative clause structures and on conjoined clauses. The relative clauses varied in type of embedding (embedded vs. nonembedded) and in the location of the gap (subject position vs. object position). There were two control groups: Wernicke-type aphasics and normal subjects. The findings from a sentence-picture matching task indicated that agrammatic aphasics were able to process complex syntactic structures, as evidenced by their well-above chance performances. The success rate varied across different types of relative clauses, with object-gap relatives yielding more errors than subject-gap relatives in all groups. Each group showed the same pattern of errors: agrammatic subjects were distinguished from Wernicke subjects and normal subjects only in quantity of errors. These findings are incompatible with the view that the agrammatics are missing portions of the syntax. Instead, their comprehension deficits reflect varying degrees of processing impairment in the context of spared syntactic knowledge. PMID- 7788347 TI - Visual word activation in pure alexia. AB - A patient with pure alexia (DM) is shown to perform rapid and accurate lexical decisions for common words without the ability to recover their complete identity. We provide evidence using a speeded decision task that DM is not forced to rely on a laborious analysis of individual letter forms when judging the lexical status of orthographic patterns varying in length, though he clearly must use this approach to fully identify a word for explicit report. By contrast, the ability to rapidly classify a word apparently does not extend to judgements of its superordinate category. DM makes semantic decisions for visual words by adopting the same inefficient procedure he uses for verbal report of their identity. The results provide further constraints on the functional deficit responsible for pure alexia. We argue that DM is able to monitor the overall activation of word units without achieving full identification and that such a process may be a characteristic of the normal reading mechanism. PMID- 7788348 TI - Acclimation of a non-indigenous sub-Arctic population: seasonal variation in thyroid function in interior Alaska. AB - Total, as well as free, T4 and T3 levels were obtained over four seasons for young male infantry soldiers assigned to interior Alaska. Significant seasonal variations were found in both T3 and T4. Total T4 and T3 levels were highest in winter, while free T4 and T3 levels were highest in early spring. Correlations with melatonin levels from a concurrent study showed an association between late day (17.00) mean spot melatonin levels during the preceding summer and T3 levels in winter and spring. Differences in seasonal T4 and T3 levels between indigenous and newly arrived people in the sub-Arctic may be related not only to cold acclimation but also to light. PMID- 7788349 TI - Calcium-dependent regulation of membrane ion permeability in a cell line derived from the equine sweat gland epithelium. AB - We measured the rates of 125I- and 86Rb+ efflux from preloaded, cultured equine sweat gland cells. The calcium ionophore ionomycin increased the efflux of both isotopes. Anion efflux was unaffected by Ba2+, but this cation inhibited 86Rb(+) efflux, suggesting that [Ca2+]i-activated potassium channels were present. Activation of these channels was not, however, important for the efflux of anions. We measured 125I- efflux from valinomycin-depolarised cells in which anion cotransport was inhibited. Changes in 125I- efflux reflect changes in anion permeability under these conditions, and ionomycin caused a clear permeability increase that was abolished by the anion channel blocker diphenylamine-2 carboxylate. ATP and UTP increased the efflux of both isotopes, suggesting that type P2U purine receptors allow these nucleotides to regulate membrane permeability. PMID- 7788350 TI - In situ degradation and absorption of [15N]urea in chicken ceca. AB - [15N]Urea was introduced (in situ) into a ligated cecal pouch of chickens to determine if it is degraded therein and absorbed into the blood as ammonia during the following 60 min. A mean of 49% of the introduced urea-15N was recovered from the blood of the mesenteric vein draining the cecal pouch and 26% was recovered from the cecal lumen fluid. Of the urea-15N introduced into the pouch, 4%, 2%, 15% and 5% were detected as urea, ammonia and non-protein fractions, except urea and ammonia, and proteins in the lumen fluid, respectively. Non-protein-15N, except urea and ammonia, protein-15N, urea-15N and ammonia-15N values recovered in the cecal venous blood were 10%, 19%, 18% and 2% of the introduced 15N, respectively. Urea concentration in the cecal venous blood increased from 0.71 mg to 3.13 mg per 100 ml for the first 15 min after introduction of urea-15N (P < 0.01) then decreased until 60 min. No significant change was found in blood ammonia concentration, however, despite a small increase during the period 15-45 min after urea-15N introduction. Ammonia-15N increased in the caecal venous blood for the first 30 min then decreased to a plateau level of 43% of the peak level. The rates of increase of urea-15N and non-protein-15N concentrations attained maxima in the blood as early as 15 min, then decreased linearly (P < 0.05). It is concluded that, although urea is actively degraded to ammonia in the ceca, it is mostly absorbed from the ceca, not in the form of ammonia, but as protein, urea and amino acids. PMID- 7788351 TI - Outward chloride/potassium co-transport in insect neurosecretory cells (DUM neurones). AB - The mechanism underlying outward chloride transport in the cell body and in the neuritic field of cockroach Dorsal Unpaired Median (DUM) neurones was assessed using the intracellular microelectrode technique. The chloride equilibrium potential was indirectly estimated from the reversal potentials of responses to gamma-aminobutyric acid (GABA) pressure ejections and of inhibitory postsynaptic potential (IPSP) evoked by electrical stimulation of the anterior connectives. Changes in intracellular chloride concentration [Cl-]i following various treatments were estimated from the amplitude changes of soma GABA responses and IPSP. Decreasing external Cl- concentration reduced the amplitude of GABA mediated inhibitory events without affecting the membrane potential. Cl-/K+ co transport was assessed by increasing external K+ concentration. The rate of outward Cl- movement was reduced furosemide but not by SITS or DIDS. All these results suggest that Cl- is not passively distributed in DUM neurones and that an active outwardly directed Cl-/K+ co-transport is implicated in the regulation of [Cl-]i. PMID- 7788352 TI - Effect of sera from lean and obese pigs on the differentiation of porcine adipose stromal-vascular cells in culture. AB - Primary cultures of stromal-vascular (S-V) cells from adipose tissue of new-born pigs were used to evaluate the characteristics of four sera obtained from male and female genetically lean or obese pigs weighing 50-60 kg. (2) Lean pig sera (LPS) stimulated greater levels of sn-glycerol-3-phosphate dehydrogenase (GPDH) activity in cultured cells than obese sera (OPS). Male LPS tended to promote higher GPDH specific activity than female LPS or male and female OPS. When GPDH was expressed on a per DNA basis, male LPS significantly (P < 0.05) increased GPDH per unit DNA compared with female LPS or male and female OPS. PMID- 7788354 TI - Protecting your baby against infection. PMID- 7788353 TI - A simulated insect diet as a water source for quail: effects on body mass and reproduction. AB - Compared with control birds receiving ad libitum free-water, the total water intake of male and female northern bobwhite declined when only mealworms were available as a source of water. Male northern bobwhite sustained tissue mass and reproductive function with mealworms as their only source of water. Female northern bobwhite could not sustain body, ovary, and oviduct mass, and rate of egg production with mealworms as their only source of water. We suggest that, without free-water, breeding females require a diet with a water:dry matter ratio of greater than 1:1.29 (> 44% water). PMID- 7788356 TI - Misdiagnosis, abortion and pregnancy. PMID- 7788355 TI - Demystifying the research process in education. AB - A well-developed base of empirical research is essential for accountable midwifery practice. Midwives need to develop 'research confidence'. The research process is explained sequentially from identification of the research problem, through literature review, research design, methodology, data collection and analysis. Research will enable the midwifery profession to develop further by uncovering the knowledge embedded in practice and in the education and management of midwives. PMID- 7788358 TI - Natural family planning. AB - Natural family planning (NFP) methods can be effective if taught well and practised by well-motivated couples. Midwives should be able to give couples an understanding of the basic principles of the methods. The observable signs of the fertile cycle are changes in basal body temperature, in the consistency of cervical mucus and in the texture and position of the cervix. Practised properly the ovulation method can have a failure rate of as little as 2.2 pregnancies per 100 woman-years. The ovulation method is a suitable method for mothers who have breastfed to detect the onset of ovulation. PMID- 7788357 TI - Brave new world? AB - Arguments in favour of embryo research Prevention of congenital defects. Reduction in number of miscarriages. Better understanding of infertility. Arguments against embryo research Morally unacceptable to take potential human life. The 14-day limit on research is arbitrary. Fears about the creation of 'superspecies' and 'designer babies'. Fear of embryo 'trade' in which embryos are bought and sold. PMID- 7788360 TI - Degree courses--why tread the academic path? PMID- 7788359 TI - Intention and reality in infant feeding. AB - Eighty women in a Nottingham practice completed antenatal and postnatal questionnaires about breastfeeding: 94% agreed that breastmilk was better than infant formula, but only 76% intended to breastfeed. The study confirms previous reports that primiparous women have a higher breastfeeding failure rate (45% had stopped by eight weeks). Women who gave later first feeds, or who were offered supplementary feeds in the postnatal ward, were more likely to be bottlefeeding at eight weeks. Hospital stays of less than 24 hours were strongly associated with successful feeding. Mothers receive little breastfeeding support from family or friends in the immediate postnatal period. PMID- 7788362 TI - The maternity care of Muslim women. AB - There are approximately 1.7 million Muslims in the UK. Followers of Islam observe certain religious and cultural practices during pregnancy and childbirth which midwives need to know and understand. Husband or children should not be used as interpreters as it is culturally unacceptable for many Muslim women to talk about intimate matters in front of their families. Midwives should not make assumptions when offering pain relief - in Islam pain is accepted as a natural part of childbirth. There may be some misconceptions about breastfeeding (for example, that colostrum is 'unclean'), and Muslim mothers - like all new mothers - need education and support. PMID- 7788361 TI - Ultrasound--routine practice or practised routine? PMID- 7788363 TI - Getting ready for the big day. PMID- 7788364 TI - Choice and control for the disabled mother. AB - One-to-one maternity care is most appropriate to the disabled woman's needs. The midwife should find out about the sources of help available to the disabled mother--lay sources of support and information should be tapped as well as professional expertise. Vaginal delivery should not be ruled out and is possible in the majority of cases. While tiredness is a problem for any new mother, midwives should guard against 'taking over' too much responsibility from the disabled mother in the mistaken belief that they are 'helping'. PMID- 7788365 TI - Getting to know your client. AB - Continuity is important in many aspects of life, but particularly during pregnancy and childbirth when a woman is experiencing physical and emotional upheaval. Midwives need to explore the allocation of resources to ensure continuity of care. A caseload system in which a midwife takes on about 36 women a year offers the client continuity and the midwife a satisfying working style which fits in with her own needs. A caseload may include high-risk pregnancies, which may provide the midwife with learning experience. Teaming up with others is the best way to run a caseload, and would leave enough midwives to provide expert staff on labour and postnatal wards. PMID- 7788366 TI - Continuing education--a choice between affluence and deprivation. AB - The study sought to identify reasons why initial enthusiasm for in-service training was not reflected in actual attendance. An interview and questionnaire survey of 61 midwives in a London health authority assessed their perceptions of, motivation for and participation in continuing professional education (CPE). The midwives surveyed appreciated the need for CPE, kept up with professional reading and took part in a wide range of educational activities. Managers and staff midwives were the poorest attenders at study days and training sessions, which may have adverse consequences for their development. It is suggested that CPE improves clinical standards and raises morale (a cycle of affluence) and that it may also prevent stress and 'burnout'. PMID- 7788367 TI - Vaginal birth after lower segment caesarean section. AB - One delivery in eight in the UK is by caesarean section. Women who have had a previous caesarean section may approach a midwife in subsequent pregnancies because they want more control over their labour. Vaginal birth after caesarean section (VBAC) is a safe option for women with a lower segment scar. Factors associated with a favourable outcome include spontaneous labour and freedom of movement during labour. Factors hindering successful outcome include reduced mobility, use of oxytocin, and time limits set on progress of labour. PMID- 7788368 TI - Diet and atopic eczema. PMID- 7788369 TI - Good nutrition for the vegetarian mother. AB - A pregnant or nursing vegetarian mother needs to be aware of the need to vary her diet because the nutrients that she would otherwise get from meat or fish are more widely scattered in foods of plant origin. Diets which exclude dairy products require more careful planning. Particular attention needs to be made to the mother's intake of iron, calcium, vitamin B12 and vitamin D. Vegetarian mothers do not show a higher incidence of complications of pregnancy, but there are some links between vegetarians and lower birthweight and earlier labour. On weaning the infant's diet should not be too bulky and should provide adequate vitamin D and B12. PMID- 7788370 TI - Midwifery in Mexico. AB - In Mexico, traditional midwives maintain the customs and rituals that have surrounded pregnancy and childbirth since pre-Hispanic times. 'Empirical' midwives are allowed to practise on the basis of experience and a minimal two week training programme. Graduate nurse-midwives usually go into general nursing and few practise midwifery, despite taking a year's specialist training in their four-year course. A project with graduate nurse-midwives demonstrated safe practice--the nurse-midwives delivered 1,500 babies with no maternal deaths and only two infant deaths in the five-year period. PMID- 7788371 TI - Insurance--why single out the independent midwife? PMID- 7788372 TI - Preconception care--are midwives in danger of missing the boat? PMID- 7788373 TI - The midwife and risk management at work. PMID- 7788374 TI - Midwives' invasive cuts. PMID- 7788375 TI - Reliable or liable? PMID- 7788376 TI - Your baby's first solid foods. PMID- 7788377 TI - Breastfeeding--midwives' personal experiences. AB - 99% of midwife mothers surveyed had a positive attitude to breastfeeding. 82% of these midwives considered that they had been successful in their attempt to breastfeed their own babies. 66% felt that the theory of breastfeeding they learned was applicable in practice. Of those for whom theory was applicable in practice, 76% felt that their theoretical knowledge also contributed to a positive personal experience of breastfeeding. The factors which contributed to successful breastfeeding were a relaxed approach, a positive attitude, determination and good support from partners and other midwives. The factors which contributed to unsuccessful breast-feeding were breast problems, fatigue, and poor milk supply. Midwife mothers would have appreciated more support with breastfeeding-many felt that they were left to cope on their own because they were health professionals. PMID- 7788379 TI - Handle with care. AB - 25% of all midwives have taken sick leave because of back injury. The onus is on the employer to see that employees are not made to undertake risky manual handling work. The place of confinement should be checked beforehand for suitability and safety. Temporary staff are covered by the risk assessment process, but independent midwives are not. PMID- 7788378 TI - How effective is antenatal education? AB - Ideal opportunities exist to offer women information during routine antenatal and postnatal care. Within the present antenatal system the midwife may not be using her teaching skills, or those skills may be out of date with modern developments. Education about childbirth could begin in schools. The midwife could also fulfil another valuable role, as mediator, providing parents with links with each other. Midwives should remember that parents have a lot to offer them as a resource. PMID- 7788381 TI - Individualised care--from blueprint to practice. AB - The first task was to develop a midwifery model, which initially meant establishing a philosophy of midwifery care. The next task was to consider documentation to support the system. The third part of the working group's remit was to educate their peers about the system. After implementation of the system, evaluation will be necessary. PMID- 7788380 TI - Maternity care for the visually impaired. AB - Midwives should not express doubts about a blind woman's ability to cope but try to boost the woman's confidence and encourage her to build on her skills. The mother needs to understand that as her abdomen enlarges and her centre of gravity shifts, she may find it more difficult to assess her own body space and her relationship to other objects. Blind women appreciate continuity of care from a small number of known professionals and may prefer a home birth or domino scheme. For those who go to hospital, help with negotiating busy waiting areas, pulling up chairs and getting into bed is likely to be welcomed. The support of another blind mother is invaluable as experiences can be shared. PMID- 7788382 TI - Caesareans on the rise--a cause for concern? AB - The number of caesarean sections performed in the UK has increased nearly threefold since 1973. Improvements in the safety of the procedure and in neonatal intensive care may account for this increase. Caesareans are being performed increasingly for breech presentations. Fear of litigation has been cited as a reason for the increase. Midwives should be working with the pregnant woman long before the question of a caesarean arises. PMID- 7788383 TI - Improving management of miscarriage and stillbirth. PMID- 7788384 TI - Maternal death--new figures. PMID- 7788385 TI - The Baby Friendly Hospital Initiative UK. PMID- 7788386 TI - The midwives' birthday. PMID- 7788387 TI - How to make your home safe for your new arrival. PMID- 7788388 TI - Safe motherhood in the United Kingdom. AB - The Safe Motherhood Initiative (SMI) is a global effort to reduce maternal mortality and morbidity. The target is to reduce maternal deaths by at least half by the year 2000. The SMI aims to enhance the quality and safety of women's lives through the adoption of a combination of health and non-health strategies. The SMI places special emphasis on the need for better and more widely available maternal health services, the extension of family planning education and services, and effective measures aimed at improving the status of women. Activity within the SMI may take many forms: Increasing awareness of the dimensions of the problem and the need for action. Strengthening maternal health services. Training of health workers and others. Facilitating educational and economic opportunities for women. Research, particularly operational research. Partners within the SMI are governments, agencies, non-governmental organisations and other groups and individuals who stimulate and participate in efforts likely to reduce the number of women suffering and dying as a result of pregnancy and childbearing. PMID- 7788389 TI - The Southampton Wave. AB - The course planning team at Southampton University College of Midwifery wanted to offer a diploma course which reflected the realities of midwifery education in the clinical setting. For this a curriculum model--The Wave--was developed. The Wave is not a static model, but reflects the changes a midwifery curriculum must absorb in context and circumstances. Allocation of students to clinical areas is linked with course content, allowing direct application of theory to practice and practice to theory. PMID- 7788390 TI - Slimming and fertility. AB - Severe reducing diets cause low levels of progesterone, slowing down follicular growth, inhibiting the surge of luteinising hormone (LH) and preventing ovulation. If less severe, slimming may depresses hormone levels by producing too small a corpus luteum and may result in a miscarriage. A reducing diet over a longer period may also affect fertility. Women planning pregnancy should be advised on the regularity as well as the adequacy of meals during the preconception period. A woman's nutritional status may be adequate for fertility but inadequate to produce a baby in the optimum birthweight range. There is a recovery period from amenorrhoea when it is wise not to conceive. PMID- 7788391 TI - The duration of the second stage of labour. AB - Fetal outcomes following extended second-stage labour include respiratory acidosis, lower umbilical vein and artery pH, lactacidaemia and early neonatal seizures. Maternal outcomes following extended second-stage labour include postpartum haemorrhage, puerperal fever, backache, musculoskeletal problems, stress incontinence and denervation of the pelvic floor. It is suggested that intervention should be based on the use of judgement and skill rather than strict adherence to timetables. PMID- 7788393 TI - Mothers in prison. PMID- 7788394 TI - Self-administration of castor oil. PMID- 7788392 TI - Alternative therapies offer more say in care. AB - Alternative medicine is holistic in its approach to the individual. Orthodox medicine, in contrast, is biomedical, viewing the body mechanistically. Alternative therapies are not without risk, and many are an unknown quantity. Mothers often feel that their own wants and values are disregarded because of professional or administrative pressure. Midwives should not prescribe alternative medicines or practise any therapies unless properly trained and then only if it is not in breach of hospital or health authority policy. Increasingly, midwives are involved in formulating new policies, so enabling the promotion of beneficial change. PMID- 7788395 TI - Midwifery-managed units. AB - Midwives involved in the establishment of a midwifery-managed unit were given the opportunity to express their concerns anonymously. The principal areas of concern they identified were: Risks to mother and baby. Transfers from the unit to the district general hospital. Refusals by clients. Indemnity, litigation and protection by management. Prescribing, training and updating. PMID- 7788396 TI - Choice, informed choice or no choice? PMID- 7788397 TI - What PREPP means to midwives. PMID- 7788398 TI - Look after yourself. PMID- 7788399 TI - Sound choices: part 1: principles and process. PMID- 7788400 TI - Child sexual abuse, labour and delivery. PMID- 7788402 TI - Welcome to the antenatal day unit. PMID- 7788403 TI - The Optical Memory Card. PMID- 7788401 TI - Antenatal screening for Down's syndrome. PMID- 7788405 TI - The midwives' voice. PMID- 7788407 TI - LTC law: nursing documentation in the courtroom. PMID- 7788404 TI - What happens when the midwife is ignored? PMID- 7788408 TI - TQM in action ... the experience of a nursing documentation project team. AB - This is the second article in a two-part series that describes the implementation of TQM at the Jewish Home of Rochester, New York, a 362 bed long term care facility. The first article gave an overview of the implementation process in the organization. This article describes the work of one of the initial project teams. PMID- 7788406 TI - Midwifery in Indonesia: a professional snapshot. AB - In 1988, Indonesia had the highest maternal mortality rate in South East Asia, but the Government's commitment to reducing this has already demonstrated a measure of success. Initiatives include: use of voluntary healthcare workers (kaders) in the local community family planning initiatives raising awareness of the status of women in society by the appointment of a Minister for Women's Affairs. The commitment of both the government and midwives to promoting safe motherhood in Indonesia should make a significant contribution to achieving the WHO aim of halving the maternal mortality rate by the year 2000. PMID- 7788409 TI - Across the world ... notes from China. Part III. PMID- 7788410 TI - Medicare cuts can affect us all--as citizens and as health care professionals. PMID- 7788411 TI - AIDS in the nursing facility ... staff considerations. PMID- 7788412 TI - Managing the front line of infection control: handwashing. PMID- 7788414 TI - Is anyone watching? PMID- 7788413 TI - Do we still need the rules? PMID- 7788415 TI - Evaluating nursing home employees: using the information to improve employee performance. PMID- 7788416 TI - Director's dialogue. PMID- 7788417 TI - New draft guidelines for isolation precautions. PMID- 7788418 TI - Across the world. PMID- 7788419 TI - Nurses raise their voices for safety of patient care and conditions of practice! PMID- 7788420 TI - Post-accident communication: practical tips designed to diffuse anger. PMID- 7788421 TI - Multiple superinfections fail to activate defective human immunodeficiency virus 1 (HIV-1) infection of rabbits. AB - Superinfection of human immunodeficiency virus (HIV)-1-infected rabbits with Treponema pallidum, Mycobacterium avium, herpes simplex, Candida albicans, Mycoplama incognitus, and malignant catarrhal fever virus, as well as irradiation or cortisone treatment, fails to activate production of infectious virus. For up to 6 months after infection of rabbits with HIV-infected cells or free virus, there are neither clinical symptoms nor positive laboratory tests for detection of HIV. However, after superinfection with other agents, HIV sequences may be transiently found in peripheral blood mononuclear cells by polymerase chain reaction (PCR), and multiple antibodies to HIV antigens may be detected by Western blotting. Both the PCR positivity and Western blot reactivity become negative with time after superinfection. Other than delayed healing of the skin lesions produced by T. pallidum and vaccinia in HIV-infected rabbits, there is no evidence of any immune abnormality. After death, gag sequences are detectable in the splenocytes of essentially every HIV-infected rabbit, and the splenocytes of eight of 25 infected rabbits responded by proliferation to HIV peptides. In addition, gag sequences are detectable in rabbits that are injected with lymphoid cells from HIV-infected rabbits. However, after multiple testing of both peripheral blood of living rabbits and organs of rabbits that died or were killed (spleen, brain, lymph nodes, liver, and gastrointestinal tract), no viable virus has ever been convincingly detected by in vitro cultivation with indicator cells. In contrast to some other published reports, these data indicate that HIV-1 infection of rabbits does not provide a model for AIDS pathogenesis therapy or prevention, but it may be useful as a model to study the relative resistance of a small fraction of the human population to development of AIDS after HIV infection. PMID- 7788423 TI - The prognostic value of plasma viremia in HIV-infected patients under AZT treatment: a two-year follow-up study. AB - To determine the prognostic value of plasma viremia in long-term zidovudine (AZT) treated HIV-infected patients, HIV-1 plasma viremia (PV) was quantified in 28 HIV infected patients before and during AZT long-term treatment; the follow-up also included p24 antigenemia and CD4 cell counts. The variations of these markers during the follow-up period, the correlation with the clinical outcome (progressors versus nonprogressors), and the discrepancies between PV and surrogate markers were then analyzed. A significant and stable decrease in PV titer was observed in only nonprogressors (Friedman test, p < 0.005). At the end of follow-up, 11 (73%) of the 15 non-progressors were PV responders (patients who remained or became PV- long-term), whereas all the 13 progressors were PV nonresponders (patients who remained or became PV+). These results indicated a strong correlation between PV and clinical outcome (Fischer's exact test, p < 0.0001). The persistence, increase, or reappearance of viral replication appeared to be an important predictor of poor clinical outcome in HIV-infected patients under AZT treatment. This finding could provide a rational basis to help the clinician's decision in the clinical treatment of HIV-infected patients. PMID- 7788422 TI - A prospective study of mother-to-infant HIV transmission in tribal women from India. AB - The transmission of human immunodeficiency virus type 1 from infected mothers to their babies was assessed by serologic, virologic, and clinical means. Of the 160 antibody-positive women enrolled at the beginning of the study, 13 had overt clinical symptoms (CDC stage III/IV). Termination of pregnancy was done, on request, in seven of these cases. The rest delivered prematurely. A total of 143 parturient women and their infants were followed prospectively until the babies were 18 months of age. Fifteen infants (9%) died of AIDS before 14 months of age. The remaining 128 children (91%) were alive at the end of the study period. Seventy-four seropositive children (46%) became seronegative and were considered noninfected. None of the seronegative children reverted to seropositive status despite the fact that they were breast-fed. The majority of the seropositive children (63%) became symptomatic and clinically ill during infancy. The overall mother-to-infant vertical transmission rate was 48%. PMID- 7788424 TI - Clinical evaluation of Amplicor HIV-1 test for detection of human immunodeficiency virus type 1 proviral DNA in peripheral blood mononuclear cells. AB - We report here the clinical evaluation of Amplicor polymerase chain reaction (PCR) assay for the detection of the human immunodeficiency virus type 1 (HIV-1) in peripheral blood mononuclear cells (PBMCs). Results obtained with Amplicor HIV 1 test were compared to serological status and a standard PCR assay using SK38/SK39 and oligomer hybridization with SK19. A panel of 208 well-characterized specimens was analyzed, including PBMC lysates from 47 antibody-negative high risk individuals, eight antibody-negative low-risk subjects, two subjects with acute retroviral disease, 35 asymptomatic seropositive subjects (59 samples) with CD4 counts > 400/mm3, 31 patients (46 samples) with AIDS-related complex (ARC), 30 patients (40 specimens) with AIDS, and six seropositive patients with unknown clinical status. Amplicor demonstrated a specificity of 100% and a sensitivity of 98.7%. Of the two false-negative samples with Amplicor, one was negative for beta globin amplification, whereas a dilution of the other sample turned positive for HIV-1. Inhibitors of Taq polymerase were thus believed to be responsible for the negative results. This study demonstrates that commercialized nonisotopic PCR assays reach adequate levels of sensitivity and specificity for diagnosis of HIV 1 infection and could be considered in clinical situations in which serology is not helpful. PMID- 7788425 TI - A phase I evaluation of concomitant rifabutin and didanosine in symptomatic HIV infected patients. AB - It has been suggested that didanosine (ddI) may undergo hepatic metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human immunodeficiency virus infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharmacokinetic and safety drug interaction study between rifabutin and ddI. Twelve patients completed the study. All patients received their regular ddI dose (167-375 mg) on day 1. On days 2-13 they received once-daily rifabutin (600 mg, three patients; 300 mg, nine patients) with their regular twice-daily ddI regimen. On days 14-16 they received rifabutin alone. Serial blood and urine samples were collected for 12 h on day 1 and for 24 h on days 13 and 16, and safety evaluations were made throughout the study. Average day 1/day 13 ddI pharmacokinetic ratios and 95% confidence interval values for Cmax, AUC0-infinity, Cls/F, and t 1/2, lambda z were 1.17 (0.96-1.38), 1.13 (0.99-1.27), 0.91 (0.81-1.01), and 0.97 (0.79-1.15), respectively (p > 0.05 for all comparisons; paired t test). A 20% difference in AUC0-infinity could be detected with 90% power. Also, there were no significant changes in laboratory values or electrocardiograms, or in rifabutin pharmacokinetic parameters when the two agents were coadministered. Based on the safety and pharmacokinetic assessments, rifabutin did not appear to interact with ddI. PMID- 7788426 TI - Clinical experience with atovaquone on a treatment investigational new drug protocol for Pneumocystis carinii pneumonia. AB - The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view. PMID- 7788427 TI - Score cards for AIDS care. PMID- 7788428 TI - Recent infection with human immunodeficiency virus and possible rapid loss of CD4 T lymphocytes. AB - To assess a hypothesized trend that persons recently infected with the human immunodeficiency virus (HIV) may have more rapid declines in absolute CD4 T lymphocyte (CD4+ cell) counts than those who were HIV-infected in earlier years, sequential CD4+ cell counts in three groups who had definable dates of HIV seroconversion between 1978 and 1992 were reviewed. The CD4+ cell counts examined were from some of the longest extant studies in the United States: 100 homosexual and bisexual men engaged in ongoing observational cohort studies in San Francisco, Denver, and Chicago since 1978 (Group 1); 89 persons in South Carolina infected after 1986 (Group 2); and 155 injecting drug users participating in an observational cohort study in Baltimore since 1988 (Group 3). For all groups, individually and in the aggregate, mean CD4+ cell counts declined rapidly in the first year after HIV infection and then stabilized. However, there was no clear trend for lower (or higher) CD4+ cell counts by fixed time after HIV seroconversion among those seroconverting in recent compared with earlier calendar years. These data do not support a hypothesized trend for more rapid loss of CD4 T lymphocytes--and, by implication, more pathogenic strains of HIV-1- among persons acquiring HIV infection in recent years. PMID- 7788429 TI - Incubation period of vertically acquired AIDS in Europe before widespread use of prophylactic therapies. AB - European surveillance data on vertically acquired (VA) AIDS cases were used to investigate the incubation period of AIDS in the absence of widespread prophylactic treatment and to assess the uncertainty associated with parametric estimates based on retrospective data. Nonparametric and parametric analyses, taking into account the effects of data truncation, were based on a total of 792 children diagnosed with AIDS between July, 1982, and June, 1990, inclusive. Among HIV-infected children who develop AIDS within 8 years, the nonparametric estimate of the median age at diagnosis was 34 months. If 20% of children are assumed to develop AIDS by the age of 1 year (a plausible estimate on the basis of published cohort data), the estimated median among all maternally HIV-infected children is 4.4 years, with 26% of children expected to remain AIDS free by 8 years of age. Results from the parametric (double Weibull) model support the hypothesis of a bimodal distribution, with a subgroup of children progressing rapidly to AIDS at a median age of approximately 5 months. However, neither the relative size of this group nor the median age at which AIDS develops in the remaining children can yet be estimated with any reasonable precision. PMID- 7788431 TI - Frequency of human herpesvirus type 6 (HHV-6) genome detection in AIDS-related lymphoproliferative disorders. PMID- 7788432 TI - Surveillance for the acquired immunodeficiency syndrome in Japan. PMID- 7788430 TI - Virologic and immunologic characterization of symptomatic and asymptomatic primary HIV-1 infection. AB - To define virologic and immunologic differences in patients with acute symptomatic and asymptomatic primary human immunodeficiency virus type 1 (HIV-1) infection, sequential plasma specimens were obtained longitudinally for 1-2 years postseroconversion from subjects with well-documented time of seroconversion. Thirteen of them had an acute symptomatic primary infection, eight subjects had asymptomatic primary infection and long-term follow-up, and 27 had asymptomatic seroconversion and short-term follow-up. Quantitative plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and levels of antibodies to gp120, p66, p41, p31, p24, and p17 were measured. At the time of seroconversion, there was no significant difference in HIV-1 RNA levels and CD4+ counts between symptomatic (n = 13) and asymptomatic (n = 27) subjects. Subsequently, however, establishment of low levels of plasma HIV-1 RNA was seen significantly more frequently in asymptomatic (n = 8) than in symptomatic (n = 13) primary infection; this correlated with higher levels of some (anti-gp120 and anti-p31) anti-HIV-1 antibodies and a slower decline in CD4+ lymphocyte counts. These results indicate that immunologic control of viremia early after infection may be a critical determinant to subsequent clinical course of HIV-1 infection. They also suggest that persons with acute symptomatic primary infection may generally progress to having acquired immune deficiency syndrome (AIDS) more rapidly than people with low grade symptoms or asymptomatic primary infection. PMID- 7788433 TI - Risk for Kaposi's sarcoma among Italian women with AIDS. PMID- 7788434 TI - The nonlinear effect of the initial period of high infectivity on the spread of HIV in the United States. PMID- 7788435 TI - Non-placebo controlled HIV experimental trials in prisoners. PMID- 7788436 TI - [Magnetic Resonance Imaging study of the role of the blood-brain barrier in the pathogenesis of experimental allergic encephalomyelitis: application to multiple sclerosis]. AB - Nuclear magnetic resonance imaging (MRI) proved to be, from the first, a very sensitive method, allowing the visualisation of multiple sclerosis lesions, yet which never permitted to establish a non equivocal relationship between the semeiology of such lesions and the clinical signs. The multifocal aspect of disseminated multiple sclerosis lesions is probably one of several factors accounting for this discrepancy. The study of an autoimmune disease, experimental allergic encephalomyelitis (EAE), regarded as a suitable model for multiple sclerosis in humans, has been performed using MRI in order to unravel the pathogenesis of the disease and apprehend the mechanisms responsible for the formation of multiple sclerosis lesions. The study focused on the part played by the blood-brain barrier (BBB) in the induction process of an autoimmune disease, since the central nervous system is normally screened from immunological supervision, by this barrier. Models both of acute EAE, induced by active or passive transfer of the antigen (myelin basic protein-MBP)--and chronic EAE, induced by passive transfer of MBP-specific T cells and myelin glycoproteins or MOG-specific monoclonal antibodies, have been reproduced, and their evolution followed up using high field MRI. Every time, the crucial role of the BBB was evidenced by the synchronism existing between the clinical signs, the appearance of lesions, preferentially in the most sensitive or permeable areas, and the BBB breakdown encouraged by the action of adjuvants. The physiopathological study of EAE using MRI is suggestive of the concept of systemic disease for multiple sclerosis, according to a two-step process, involving, in a first stage some primary viral or bacterial infection, causing T-cells to be sensitized to the host's own proteins by molecular mimicry, and in a second stage some bacterial infection or accidental circumstances which, resulting in a BBB breakdown, would provide immunocompetent cells with an opportunity to reach their target. PMID- 7788437 TI - [Origin of allergens in the cat]. AB - Danders and animal products have long been recognized as major allergens. One of the most common animals responsible for allergy is cat. Fel d I the major allergen has been detected in fur and a number of authors have claimed that saliva is the principal source of this major allergen and that pelt is contaminated as a result of licking during grooming. We could demonstrate that one of the major sources of Fel d I present on the skin are sebaceous glands and that the production of Fel d I is under hormonal control at least in male cats. Castration decreases significantly the level of Fel d I on the skin and the injection of testosterone reverses the phenomenon. These data lead to continue the work about the regulation of this protein and the knowledge of its biological function. PMID- 7788438 TI - [History and tradition of the military service of ambulance transportation]. PMID- 7788439 TI - [Production and proinflammatory activity of tumor necrosis factor alpha in the glomerulus]. AB - The production and the effects of tumor necrosis factor alpha (TNF alpha) have been studied in isolated glomeruli and cultured glomerular cells from animal or human origin. Glomeruli from rats injected with E. coli lipopolysaccharide (LPS) and glomeruli exposed to LPS in vitro release TNF alpha into the medium. The glomerular cells responsible for TNF alpha synthesis are mesangial cells. Production of TNF alpha is controlled by other locally produced mediators. Prostaglandin E2 and interleukin-10 are inhibitory. Hydroxyl radicals stimulate the transformation of the transmembrane form of TNF alpha into its soluble form which is secreted into the medium. TNF alpha acts on its producing cells and on the neighbouring cells. It induces contraction of mesangial cells, increases the synthesis of a variety of local mediators including prostaglandins, platelet activating factor and chemotactic agents, particularly interleukin-8. Synthesis of this cytokine implies activation of tyrosine kinase and of transcription factors, essentially NFkB. Taken together, these results suggest that TNF alpha plays a marked role in the development of glomerular injury and incite us to search for treatments inhibiting its synthesis and its effects. PMID- 7788440 TI - [Sexual mutilation in women]. AB - The sexual mutilations, a fairly topical subject, remain very frequent (between 80 and 100 millions). The excisions are in practice mainly in Africa (in at last 20 countries), but also in the Far-East and Indonesia. In some cases, such practices are very mutilative (Pharaonic infibulation). They may drag to the death, through haemorrhage or infection. The short and long term medical complications are fearful, tetanus, vesicovaginal fistulae, vaginal or vulvar sclerosis, forbidding any sexual involvement and hampering delivery. The grounds of these practices are basically customary and not religious. Women shall be subservient to men and any manhood mark, embodied by the clitoris, shall disappear. However these manoeuvres are decreasing, due to the women emancipation, and, particularly, in Africa, some leaders are aware of their graveness and are punishing heavily the excision, taking model of the French Penal Code. The immigrants, who, in France, have these mutilations undertaken, are incurring imprisonment sentences (precedents are frequent). They must comply with the French laws. PMID- 7788442 TI - [Criteria for brain death]. PMID- 7788441 TI - [Reconstruction by free jejunal transplant after circular pharyngolaryngectomy (functional results and survival)]. AB - One hundred and ninety seven patients with cancer of the hypopharynx underwent after circular resection, reconstruction with a free jejunal graft. The quality of free jejunal grafts is controlled by many investigations: clinical examination, radiography, electromyography, fibroscopy with biopsy. These investigations show that technically jejunal grafts must be short and linear to give the best functional results. Average resumption of oral intake was 14 days. Oral feeding was possible in 92% of cases. The free jejunal grafts with microsurgery are one of the more reliable procedures for reconstruction of pharynx and cervical esophagus after resection for cancer. (2 post-operative deaths and 8 grafts necrosis on 197 cases). The cumulative survival rate of 5 years was 35% for free jejunal graft. Survival depends on selection of the patients for local and nodes invasion. The quality of survival has improved. This operation must be reserved for the hypopharyngeal cancers which need a circular resection and do not invade the esophagus. The surgery is performed for a curative aim. The distant follow up of the patients is imperative: consultation every four months and then every six months: clinical examination, endoscopic, E.N.T., bronchial, and esophageal investigation. Chemotherapy and radiotherapy have specific indications. PMID- 7788443 TI - [Food-induced anaphylaxis. A new French multicenter study]. AB - The frequency of food-induced anaphylactic shocks (FIAS) has been investigated beside 46 emergency departments, 29 departments of Dermatology, and 19 departments of Intern Medicine or Pneumology. 794 A.S. have been reported. FIAS represent 10.2% of the etiologies. More than a third of them are relapsing anaphylaxis. Food allergy had been previously identified in 23.4% of cases. The allergen was present as a hidden allergen or inadvertently consumed in 30.8% of FIAS. 9.9% of the patients were asthmatic. An enhancing factor was heightened in 25.9% of cases: alcohol, exercise, simultaneous intake of aspirin, beta-blockers, conversion enzyme inhibitors. Other factors predisposing to food anaphylaxis were a cross-reactivity shared by pollens and fruit, latex and exotic fruit, house dust mites and snails, or mastocytosis. More than 15 allergens were detected: egg (11.6%), fish (10.4%), crustaceans (10.4%), milk (6.5%), fruit-latex group (6.5%), peanut and other legumes (soy, peas, lentils, guar gum...), celery, garlic, etc... The food allergen still remained unknown in 25% of cases. However, the rate of efficiency of the diagnosis reached 94% in the Allergy Units. In addition 10.2% of A.S. were considered idiopathic, raising the hypothesis of allergy to masked food allergens. Compared to a previous study from the 1982's, this survey shows a striking increased prevalence of FIAS. The frequency of recurrent anaphylaxis, occurring in one-third of cases, is also highlighted and makes plausible once more the role of masked food allergens. The authors insist upon the need of a thorough allergologic investigation in all the cases of A.S. An informative labelling about the presence or absence of food proteins which are mostly allergenic should be recommended. The need of a thorough allergologic investigation is supported not only by the incidence of FIAS but also by the incidence of idiopathic anaphylaxis: 10.2%. PMID- 7788445 TI - [Venous angiography: importance in the diagnosis of brain death. 125 cases]. AB - According to many ethical and humanitarian arguments, the diagnosis of "brain death" is more and more an emergency. The forensic criteria include abolition of consciousness, abolition of brain stem reflexes, abolition of spontaneous breathing joined to electrocerebral silence. However using EEG criteria of electrical silence may be unreliable because of technical artefacts or depressed electrical activity due to drug intoxication and hypothermia. Venous angiography was used in 125 cases: our experience proves reliability and efficiency of angiographic criteria for diagnosis of brain death. For organ transplant, it is better to be as fast as possible: transplanted organ will be better and it reduces the cost of a long useless intensive care. When it is necessary, we suggest to allow the choice between EEG and angiography. PMID- 7788446 TI - [Validity of cerebral angiography via venous route in the diagnosis of brain death]. AB - The success of transplantations relies on uninjured organs i.e., harvested before circulatory failure. At present, french law concerning cerebral death criteria (circulaire ministerielle n. 3 du 21.01.91) requires the association of clinical patterns and 2 repeated, unreactive and flat electroencephalographic (EEG) tracings. Blood and urinary samples also need to be free from any nervous system depressant drug, the patient has not to be hypothermic. These obligations are not always compatible with patients status or local organization. The consequence might be organ loss or delay in harvesting schedule. A review of the literature points out the trap in realization and analysis of EEG in this kind of intensive care patients. Angiogram, on the opposite, is influenced neither by nervous system depressant drug nor by hypothermia. As it is in some other western countries, it should be proposed as the reference. PMID- 7788444 TI - [Controlled hypercapnia: a new strategy in the treatment of severe respiratory insufficiency]. AB - Permissive hypercapnia (PHY) represents an interesting approach in critically ill ventilated patients, because it allows to ensure adequate gas exchange while avoiding the adverse effects related to excessive airway pressures. Its objective is to improve oxygenation while reducing the risk of barotrauma and circulatory impairment. This concept is all the more important when considering that in majority of lung diseases for which MV is applied, lung involvement is highly inhomogeneous, meaning that the functionally normal or near normal areas are the most exposed to the deleterious effects of overdistension. Undesired physiological effects of non massive respiratory acidosis (PaCO2 < or = 80 mmHg, arterial pH > or = 7.15) are reversible and mostly minor. This good tolerance legitimizes two strategies: firstly to accept hypercapnia in conditions such as acute severe asthma for which enforced normalization of PaCO2 would imply potentially lethal complications, and secondly to deliberately induce respiratory acidosis while using very low airway pressures and alveolar ventilation to limit or prevent overdistension lung damage in injured as well as in normal areas. When the cerebral vasodilation induced by CO2 might aggravate a preexisting intracranial disorder, PHY is obviously contraindicated. PMID- 7788447 TI - [Malignant lymphoma with medium-sized macronucleolated cells in the dog: involvement of an original cell from the marginal zone of the reactive lymph node]. AB - Among the non-Hodgkin's malignant lymphomas of the dog, which are largely dominated by the centroblastic heterogeneous type, there is an original form of malignant lymphoma which is homogeneous and diffuse, with macronucleolated medium sized cells. These cells seem to be morphologically very similar to those which constitute the majority population in the marginal zone of the secondary follicle of the lymph node in the dog, and which appear in the course of certain conditions: systemic lupus erythematosus, leishmaniasis, satellite lymph nodes in benign or malignant tumors. The aim of this study was twofold: on the one hand to establish, in the canine species, the identity of the lymphomatous cells and the reactive cells that make up the marginal zone, i.e. the filiation between the hyperplastic marginal zones and the macronucleolated malignant lymphoma with medium-sized cells, and, on the other hand, to compare this type of malignant lymphoma with those which are reputed to originate in the marginal zone in humans, for example the malignant lymphoma of the lymphoid tissue associated with the mucous membranes, and the monocytoid malignant B-cell lymphomas. Ninety four malignant lymphomas were observed between 1989 and 1994 at the Veterinary School in Lyon; these consisted of 71 cases showing medium or high-grade malignancy, 17 cases with small cells, of low-grade malignancy, and 6 cases of mycosis fungoides. Among the 71 cases of medium and high-grade malignancy, 8 were immunoblastic, 5 centroblastic homogeneous, 50 centroblastic heterogeneous, and 8 homogeneous with macronucleolated medium-sized cells. The methods used in these 94 cases were of a morphological type: cytology, histology, transmission microscopy and immunohistochemistry. The cytohistological, ultrastructural and immuno-phenotypical characteristics (CD3-, CIg-, Ki-67- phenotype) of the lymphomatous cells and the cells of the marginal zone were found to be identical, in the dog; this strongly suggests B-lineage cells which do not secrete cytoplasmic immunoglobulins and are not involved in the cell cycle. Finally, these cells seem to us to be morphologically very similar to the minority population described by Van den Oord in the marginal zone of the secondary follicles in the lymph node in humans, in certain reactive situations. PMID- 7788448 TI - [Importance of measuring exposure to the principal indoor allergens in allergic asthma]. AB - Domestic allergens, such as mite and cat allergens, are a leading cause of allergic asthma. Allergen exposure is a risk factor for sensitization. Allergens also play a major role in the development of inflammation and non specific bronchial hyperreactivity as well as in the apparition and modulation of symptomatic asthma. The development of new means of detecting allergens (i.e. immunochemical assays including monoclonal antibodies, quantitative and semiquantitative guanine measurements for mite allergens) has made possible to identify allergens sources and reservoirs. The form in which domestic allergens become airborne is important. The group I and II allergens from mites, the major cockroach allergens are carried on large particles (mean size > 10 microns diameter); in contrast, the major cat allergens are airborne on small particles (40% < 5 microns). Guanine, a metabolic excretion product of mites, is used as a marker for mite feces and is correlated with the presence of major allergens from mites. A colorimetric method (Acarex-TestR) provides a simple and inexpensive method of assaying indoor mite allergen exposure for both doctor and patient alike. By using Acarex-TestR it is possible to evaluate the mite allergen exposure for a population in a particular country. The detection of allergens sources and reservoirs, the quantification of domestic allergens has enabled the evaluation of the effect of a reduction in allergen exposure to be better assessed. Recognition of the risks, environmental control and reduction in allergen loads, should be among the objectives of asthma management. PMID- 7788449 TI - [Activity of adenosine in relation to tumor necrosis factor (TNF). Therapeutic outlook]. AB - At physiological and pharmacological doses, adenosine protects tissues against a varieties of injuries: ischemia-reperfusion, convulsions, inflammation.... We tested the hypothesis that the antiinflammatory properties of adenosine occur via a down-regulation of TNF. Agonists of adenosine receptors (ARA) and agents potentiating endogenous adenosine (APA) were evaluated for their effects on TNF production by endotoxin-stimulated human monocytes. Additionally, one of the most potent agonists, R-phenylisopropyladenosine (R-PIA), was tested on two experimental models of acute phase response, endotoxin shock and carrageenan induced plantar oedema. Several ARA and APA inhibited monocyte TNF production in a concentration-dependent manner. R-PIA and other ARA were active at micromolar concentrations. The property is pharmacologically relevant since rats receiving a lethal dose of endotoxins were protected by R-PIA and endotoxin-induced serum TNF levels were abolished by a pretreatment with R-PIA. Inhibitory effects on serum TNF production were obtained with similar doses of dexamethasone sodium phosphate and one hundred-fold higher doses of pentoxifylline. R-PIA was also found active on carrageenan-induced oedema. The anti-oedematous properties of R-PIA were associated with a marked reduction of locally-produced TNF and were also observed after the administration of dexamethasone, pentoxifylline and a neutralizing anti TNF antibody. Our results indicate that adenosine is a potent inhibitor of TNF production induced by different stimuli. This property could lead to therapeutic applications in inflammatory diseases and other in which TNF is known to play a pathogenic or aggravating role. Comparison between ARA and APA in terms of tolerance and efficacy merits further attention. PMID- 7788450 TI - A 12-step recovery program for community psychiatrists. PMID- 7788451 TI - A managed care ethical credo: for clinicians only? PMID- 7788452 TI - Protecting staff from assaults by patients: OSHA steps in. PMID- 7788454 TI - The role of primary care physicians in managed mental health care. PMID- 7788453 TI - The psychiatrist in the nursing home, Part II: Consultation, primary care, and leadership. PMID- 7788455 TI - A psychiatrist-rated battery of measures for assessing the clinical status of psychiatric inpatients. AB - Despite the increasing demand for outcome assessment measures, no published reports have provided a standardized way to assess psychiatric inpatients that includes diagnosis and observer ratings of psychopathology. This paper reviews general principles for selecting outcome assessment measures, proposes a battery of instruments based on already available measures to assess clinical status in psychiatric inpatients, reviews methods of implementing the battery in an academic inpatient psychiatric setting, and presents preliminary data on its interrater reliability, construct validity, and range of response to acute hospitalization. Preliminary results suggest that the battery may be useful for resident and medical student education and for enhancing quality assurance and continuous quality improvement. PMID- 7788456 TI - Relationships between psychiatric symptomatology, work skills, and future vocational performance. AB - OBJECTIVE: Experts do not agree on what, if any, relationships exist between diagnosis, symptomatology, work skills, and the future vocational performance of persons with severe mental illness. The objective of this study was to longitudinally examine such relationships, using a sample of clients who were attending psychosocial rehabilitation programs. METHODS: Subjects were 275 clients of three psychosocial rehabilitation programs who had expressed a vocational goal. They were assessed at intake into the study and then quarterly until they left the rehabilitation program. The variables examined included symptoms, measured by the Brief Psychiatric Rating Scale; diagnosis; work skills, measured by the Griffiths Work Behavior Scale; and vocational status at end point. RESULTS: Among subjects remaining in the study for one year, both symptomatology and work skills improved significantly. Moderately significant negative correlations were found between symptoms and work skills; subjects who became employed had lower symptom scores and higher work skills than persons who never became employed. CONCLUSIONS: Although a moderate relationship was found between symptomatology and work skills, symptoms should not be considered a proxy measure for vocational functioning among persons with severe mental illness. Participation in psychosocial rehabilitation programs appeared to have a salutary effect on symptoms and work skills. PMID- 7788457 TI - Disability compensation and work among veterans with psychiatric and nonpsychiatric impairments. AB - OBJECTIVE: This study examined the relationship of Department of Veterans Affairs disability compensation payments and employment among veterans with psychiatric disorders and veterans whose impairments were nonpsychiatric. METHODS: Data from a 1987-1988 national survey of Vietnam-era veterans (N = 1,634) were used to evaluate the relationship between compensation payments and employment. The employment activity of veterans whose application for benefits was rejected was compared with that of veterans who were awarded benefits. Multivariate analytic techniques were used to control for health status and other factors that also influence an individual's decision to work. RESULTS: Veterans who received compensation of less than $500 a month were no less likely to work than were rejected applicants. Overall, the effect of compensation payment was significant but modest: each additional $100 a month was associated with a 2 percent decline in the number of veterans who worked, a decline of an hour a week in the number of hours worked, and a reduction of $1,000 a year in estimated employment income. No significant differences were observed in the relationship between disability payments and employment among veterans with psychiatric disorders and those with other functional impairments. CONCLUSIONS: The association of disability compensation with nonparticipation in the labor force is generally small, except at high levels of payment, and is no greater for veterans with psychiatric disorders than for those with nonpsychiatric impairments. PMID- 7788459 TI - Evaluating the effectiveness of a residential rehabilitation program for homeless veterans. AB - OBJECTIVE: This study sought to evaluate the effects of a residential rehabilitation program for homeless mentally ill veterans on several measures of subjects' community adjustment. METHODS: Subjects' housing status, financial and vocational status, psychological stability, utilization of coping resources, and extent of social contacts were measured at entry into the program and at follow up six months after discharge. Data were available for 58 subjects at follow-up. Outcomes for subjects who successfully completed the program were compared with outcomes for those who did not. RESULTS: As a group, subjects assessed at follow up showed significant improvement in housing, financial, and vocational status, in severity of several symptoms of psychological and emotional distress, in utilization of some types of coping resources, and in measures of social contacts and satisfaction. However, subjects who completed the program were more likely to have improved their housing, financial, and vocational situations. CONCLUSIONS: Comprehensive residential rehabilitation programs can help homeless veterans improve several aspects of their lives and maintain stability in those areas after discharge. PMID- 7788458 TI - Service utilization and costs of care for severely mentally ill clients in an intensive case management program. AB - OBJECTIVE: The study evaluated the effects of an intensive case management model on clients' use of inpatient and outpatient psychiatric care and on the costs of care. METHODS: Ninety clients of a county mental health system who were frequent users of inpatient services were randomly assigned to either an intensive case management group, a traditional case management group, or a control group who received no particular services. Outcome variables measured over a two-year period were number of units used by clients and costs of inpatient care in county and private facilities and various types of outpatient care, including day treatment and use of an emergency psychiatric unit. RESULTS: Clients who received intensive case management had fewer inpatient days and reduced overall costs for mental health services. CONCLUSIONS: Assertive outreach and intensive case management can reduce hospitalizations of clients who are frequent users of inpatient care and can reduce overall mental health care costs. Mental health consumers employed as case management aides can play an important role in the delivery of mental health services, particularly with frequent users of inpatient care. PMID- 7788460 TI - Effects of social skills training and social milieu treatment on symptoms of schizophrenia. AB - OBJECTIVE: The study compared the effects of social skills training and social milieu treatment on symptoms of schizophrenia, particularly on negative symptoms. METHODS: Thirty-three patients aged 18 to 55 years with a diagnosis of schizophrenia were randomly assigned to a nine-week program of social skills training or social milieu treatment. Patients were assessed at three-, six-, and nine-week intervals during treatment and at follow-up using the Positive and Negative Syndrome Scale (PANSS), which measured both positive and negative symptoms of schizophrenia and general psychopathology. RESULTS: Fifteen patients completed social skills training, and 13 completed social milieu treatment. Comparison of PANSS scores at different assessment times showed that both treatments were effective in reducing symptoms, but social skills training appeared to be more effective in reducing negative symptoms. No differences were found between treatment groups in relapse rates or in symptom measures at three month follow-up. However, six-month follow-up data available only for the social skills training group showed that improvement in negative symptoms had begun to decline. CONCLUSIONS: Psychosocial approaches are a necessary component in the treatment of patients with schizophrenia, and social skills training appears to be particularly helpful. The gradual decline in improvement in negative symptoms at six-month follow-up suggests the need for more extended treatment. PMID- 7788462 TI - 18-month outcome of clozapine treatment for 100 patients in a state psychiatric hospital. AB - OBJECTIVE: The atypical antipsychotic medication clozapine is an effective treatment for refractory psychosis; however, the efficacy of clozapine when used in public mental health programs has yet to be fully characterized. This study assessed the outcome of clozapine treatment in a state hospital. METHODS: The medical records of the first 100 patients to receive clozapine in a state hospital, from six months before clozapine treatment through 18 months of treatment, were reviewed. RESULTS: The patients had chronic psychotic disorders that had responded poorly to treatment with conventional antipsychotic medication. Eighteen months after beginning clozapine, 45 patients were much improved, and 18 were somewhat improved. All except one of the improved patients were continuing clozapine treatment. Forty patients were living in community settings, 59 remained hospitalized, and one had died of an illness unrelated to clozapine. Violent episodes in the hospital decreased during the first six months of clozapine treatment. Thirteen patients had one or two seizures while taking clozapine, 12 of whom successfully continued clozapine treatment. One patient developed agranulocytosis, and one developed leucopenia; each recovered fully after clozapine treatment was discontinued. CONCLUSIONS: Clozapine was an effective treatment for refractory psychotic disorders when given as a part of routine state hospital treatment. PMID- 7788461 TI - New directions in research on involuntary outpatient commitment. AB - OBJECTIVE: Involuntary outpatient commitment has been used as a method of improving tenure in community programs for individuals with severe and persistent mental illness. This paper reviews literature on research about involuntary outpatient commitment and suggests questions and methods for future research. METHODS: Literature describing research studies of involuntary outpatient commitment, located by searching MEDLINE and following up references cited in relevant articles, was reviewed with attention to patient characteristics and diagnostic, treatment, and outcomes measures. RESULTS: Involuntary outpatient commitment appears to provide limited but improved outcomes in rates of rehospitalization and lengths of hospital stay. Variability in community treatment makes interpretation of other types of outcome difficult. Few studies specifically identify results among patients with severe and persistent mental illness. CONCLUSIONS: No studies have examined the extent to which outpatient commitment affects compliance and treatment when essential community services such as case management are consistently and aggressively provided, nor have studies controlled for potentially confounding factors such as treatment and nontreatment effects, including informal coercion. A randomized trial of involuntary outpatient commitment should be useful in evaluating the effectiveness of this type of intervention. PMID- 7788463 TI - Projections of housing disruption among adults with mental illness who live with aging parents. AB - OBJECTIVE: The need to plan for the future housing needs of adults with serious mental illness who reside with aging parents is an issue of increasing importance to mental health policy makers as well as family members. This study provides estimates of the number of adults with severe and persistent mental illness in New York State who could be expected to experience housing disruption because of their parents' death. METHODS: Demographic modeling methods were applied to data from a variety of sources, including surveys of mentally ill adults receiving public mental health services in New York State and demographic statistics on the general state population. RESULTS: An estimated 13,400 to 49,600 adults with severe and persistent mental illness who receive services from the public mental health system in New York State reside with one or both parents. Within this group, between 300 and 1,200 adults could have been expected to experience housing disruption due to parental death each year between 1990 and 1994. Demographic trends indicate that through 2009, these disruptions will increase at a faster rate than growth in the state's general adult population. CONCLUSIONS: Additional housing with mental health supports and other programs will be needed to accommodate the growing number of severely mentally ill adults whose housing may be disrupted because of the death of their parents. PMID- 7788464 TI - A survey of new long-stay hospital patients in an Irish health board area. AB - OBJECTIVES: The aims of this study were to determine the number and rate of accumulation of new long-stay hospital patients in one of Ireland's eight health board areas, to describe their demographic and clinical features, and to assess their needs in relation to possible community placement. METHODS: Demographic and clinical information was obtained on all patients over age 17 who had been continuously hospitalized in area hospitals for more than one year and less than six years on the census day of March 1, 1992. The Community Placement Questionnaire was used to rate the patients' social functioning, problem behavior, physical disability, social contact, and needs for accommodation and day care. RESULTS: The survey identified 175 new long-stay patients, mainly middle aged to elderly. Schizophrenia was the most common psychiatric diagnosis. The bed occupancy rate for these patients was 14 per 100,000 population, and the annual accumulation rate was 2.3 per 100,000 population. CONCLUSIONS: New long stay patients were chronically ill with significant psychiatric and social disabilities. Involuntary patients were overrepresented in the group. Two-thirds could be placed in the community if facilities were available and had sufficiently high staffing levels. PMID- 7788465 TI - Depression and anxiety disorder among older male inmates at a federal correctional facility. AB - The conditions of incarceration and the sociodemographic and health characteristics of 95 older male inmates of a federal correctional facility were studied to determine the relationship of such variables to rates of psychiatric disorder among older male inmates. A total of 51 inmates (53.7 percent) met one month criteria for psychiatric disorder, a much higher rate than among a community sample of men in the same geographic area. Compared with inmates without such disorders, inmates with disorders were likely to be younger, to have a history of psychiatric disorder and substance abuse, to have poorer physical health, to have impaired social support, and to be serving a determinate sentence with no possibility of parole. Few were receiving treatment while incarcerated. PMID- 7788466 TI - Prevalence and symptoms at onset of bipolar illness among adolescent inpatients. AB - The records of 236 adolescents (116 males and 120 females) admitted to an inpatient psychiatric unit over an eight-year period were retrospectively reviewed to determine the characteristics of patients with a discharge diagnosis of bipolar disorder. Forty-two patients had a diagnosis of an affective disorder, including 18 patients (nine males and nine females) with bipolar disorder. Mean age at onset of illness for patients with bipolar disorder was 15.7 years, and their onset of illness was likely to have been associated with psychotic symptoms. On admission, they were more likely to show symptoms of mania than of depression. PMID- 7788467 TI - Age as a factor in identifying young adult chronic patients who are difficult to treat. AB - Age younger than 35 years has been used as a factor in identifying young adult chronic mentally ill patients, a group considered difficult to treat due to their rebelliousness, lack of insight about their mental illness, and increased likelihood of showing symptoms of borderline or antisocial personality disorder. In a sample of psychiatric outpatients, the authors found that a subgroup of patients under age 35 fit this profile, while other patients under age 35 and nearly all patients over age 35 did not. The authors conclude that age is a legitimate factor in identifying a subgroup of challenging patients and that such patients may outgrow many troublesome characteristics as they age. PMID- 7788468 TI - Violence and mental illness. PMID- 7788469 TI - Studying violent behavior. PMID- 7788470 TI - Containing patient violence. PMID- 7788471 TI - Ethical managed care. PMID- 7788472 TI - 19th-century medicines. PMID- 7788473 TI - Research funding for child and adolescent mental disorders falls well below goals in national plan. PMID- 7788474 TI - Clinton's 1996 budget proposal would consolidate most SAMHSA programs, give states more control. PMID- 7788475 TI - NAMI outlines national standards for protecting research subjects with serious mental illness. PMID- 7788476 TI - Research collaboration on HIV dementia. PMID- 7788477 TI - Clinical Research Meeting. San Diego, California, May 5-8, 1995. Abstracts. PMID- 7788478 TI - Competencies and problems reported by parents of Greek and American children, ages 6-11. AB - This study compared parent-reported competencies and behavioral/emotional problems in demographically-matched samples of Greek and American children, ages 6-11. Parents of 356 children of each nationality completed the Child Behavior Checklist (CBCL). Competence scores were higher for American children, except on Academic Competence, where scores were higher for Greek children. Greek scores were significantly higher than American scores on the Withdrawn, Anxious/Depressed, Attention Problems, Delinquent Behavior, Aggressive Behavior, Internalizing, Externalizing, and Total Problem scales. On the Anxious/Depressed syndrome, nationality accounted for 14% of the variance. There were few main effects for sex and age and fewer interactions. The higher problem scores in the Greek sample were partly due to the tendency of Greek parents to use extreme item scores. When items were scored present v. absent, Greek scores were higher only on Withdrawn, Anxious/Depressed, Internalizing, and Total Problems, while American scores were higher on Somatic Complaints and Thought Problems. Nationality differences in rates of referral for mental health services and sample differences in exclusion criteria for prior mental health services may have contributed to differences in problem scores. Results are compared to findings from other cross-cultural studies. PMID- 7788479 TI - Behavioral problems of adolescents with chronic physical illness: a comparison of parent-report and self-report measures. AB - This study reports on the extent of behavior problems in Israeli adolescents suffering from chronic illness. A comparison was made between parent-reported and self-reported behavioral symptomatology using the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). 103 outpatients, aged 11-16 years, suffering from cystic fibrosis (CF), asthma, or hematological/oncological conditions were assessed. Healthy adolescents and adolescents referred for psychiatric assessment comprised the comparison groups. Parent- and self-reports were significantly positively correlated in each group (all chronically ill children r = .22; Healthy group r = .27; psychiatric group r = .50), but the correlations were particularly low (and non-significant) in younger adolescents with hematological/oncological conditions or HCF., pointing to the need for physicians to include parents' and adolescents' viewpoints in their assessments of these adolescents' psychosocial state. The mean number of parent-reported and self reported behavior problems in the illness groups was no different from that of the Healthy group but significantly lower than that of the psychiatric group. PMID- 7788480 TI - Family stress, family functioning and emotional/behavioural problems following child psychiatric treatment. AB - This study assesses family stress, family functioning and emotional/behavioural problems in a sample of 80 formerly daytreated or residentially treated boys after a mean discharge period of four years. Family stress was assessed with a Questionnaire of Life Events (QLE) and family functioning with the Family Adaptability and Cohesion Evaluation Scales (FACES). Emotional/behavioural problems were measured with the Child Behavior Checklist (CBCL). The results showed that there were significant relationships between the QLE, FACES and CBCL scores. In particular, experiencing less negative life events and a more rigid type of family functioning appeared favourable with respect to several types of behavioural problems. When the interrelationships between the family factors and other factors such as age and socio-economic status were taken into account statistically, the number of negative life events appeared the most influential family factor. PMID- 7788481 TI - An epidemiological and clinical approach to adolescent suicide. A comparison between suicidal and non-suicidal clinical groups in a health foundation center for French students. AB - Suicidal behaviour among young people represents a major public health problem. This study seeks to compare the major sociological, clinical, schooling and family features of suicidal and non-suicidal subgroups of adolescents hospitalised in the Health Foundation Center for French Students of neufmoutiers en Brie (France). All these adolescents suffered from the severe mental disorders. The adolescents from the suicidal subgroup presented significantly fewer psychoses and more mood disorders than those of the non-suicidal subgroup. Half of the patients from the suicidal subgroup presented some features of personality disorders, mostly borderline personality disorders. Nevertheless, their global functioning was more frequently improved between admission and discharge than was the case for the non-suicidal group. PMID- 7788482 TI - Case report: successful treatment of a case of extreme isolation. AB - Tom, aged 10, presented as a stiff, plump boy with a very awkward gait and a completely blank facial expression. He was terrified of other children and could allow no one closer than an arm's length away from him. It transpired that for most of his life he had been kept "safe" in his bare room by his parents whose firstborn child had died. After 8 years of treatment he is now studying at a university and although he lives at home he seems to have made some friends. His facial expressions and tone of voice are now appropriate. PMID- 7788484 TI - 5th Vienna Shock Forum. Vienna, Austria, May 7-11, 1995. Abstracts. PMID- 7788483 TI - Case report: concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease. AB - Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed. PMID- 7788485 TI - What is a perinatal cardiologist? PMID- 7788486 TI - Study of the early development of the hindbrain. PMID- 7788487 TI - Training in invasive fetal procedures. PMID- 7788488 TI - Early development of the hindbrain: a longitudinal ultrasound study from 7 to 12 weeks of gestation. AB - Twenty-nine healthy pregnant women were examined by transvaginal ultrasound to evaluate embryonic development in vivo between 7 and 12 weeks of gestation. The rhombencephalon with its fourth ventricle, the cerebellum and the choroid plexuses of the fourth ventricle were identified and measured. The cavity of the rhombencephalon, the future fourth ventricle, was always visible from 7 weeks, initially lying superiorly in the head of the embryo. The cerebellum and the choroid plexuses of the fourth ventricle became distinguishable during week 8. The volume of the rhombencephalic cavity was estimated. The shape and size of these rhombencephalic structures, their position in relation to each other and their relation to other brain structures changed specifically during the embryonic and early fetal period. This sonoembryological development corresponded to the descriptions in classical embryological literature. PMID- 7788489 TI - First-trimester ultrasound screening for fetal aneuploidies in women over 35 and under 35 years of age. AB - In a prospective screening study, the utility of the thickness of first-trimester simple hygroma in sonographic screening for fetal chromosomal aberrations was examined. A total of 3380 women, 1280 of whom were 35 years or over, and 2100 of whom were under 35 years, were screened by ultrasound at 9-12 weeks of gestation. The thickness of fetal nuchal simple hygroma was measured. Women over 35 years of age underwent transabdominal chorionic villus sampling (CVS). In women under 35 years of age, CVS was offered only if the thickness of nuchal hygroma was at least 3 mm, or in cases of parental chromosomal abnormalities. A total of 46 chromosomal anomalies were detected, of which 43 (93.5%) showed simple hygroma. The incidence of first-trimester simple nuchal hygroma in pregnancies of women over 35 and under 35 years of age was 5.4% (69 cases) and 1.28% (27 cases), respectively, and the percentage of chromosomal abnormalities was 2.9% and 0.43%, respectively. The risks of trisomies and poor pregnancy outcome were increased at larger sizes of first-trimester simple hygroma. A sensitivity of 93.5% and a specificity of 98.4% of the method were found. Using a measurement of first trimester simple hygroma of > or = 3 mm to identify pregnancies at risk for chromosomal anomalies at 9-12 weeks of pregnancy is a useful method for selection of women with high and low risk for aneuploidy. PMID- 7788490 TI - Fetal suprarenal masses: sonographic appearance and differential diagnosis. AB - We present eight cases of suprarenal masses detected sonographically in fetuses of 20-41 weeks. The appearances of the masses included hyperechoic (n = 2, both pulmonary sequestrations), solid isoechoic (n = 1, a neuroblastoma), purely cystic (n = 3, two neuroblastomas, one enteric cyst) and mixed or complex (n = 2, one neuroblastoma and one renal cyst). Three of the fetuses with neuroblastoma had normal scans in the second trimester, and in all four the neuroblastomas were detected after 36 weeks. This study demonstrates the differential diagnosis of suprarenal masses in fetuses. Neuroblastomas can have a solid, purely cystic or complex sonographic appearance. Although not all suprarenal masses are neuroblastomas, the newborn with a prenatally detected suprarenal mass should be evaluated for the possibility of a neuroblastoma, since early diagnosis of this malignancy can be curative. PMID- 7788491 TI - Routine prenatal ultrasound screening for fetal abnormalities: 22 years' experience. AB - We describe the results of routine obstetric ultrasound examination over a period of 22 years (1970-91) at the Institut Universitari Dexeus, Barcelona, Spain. A total of 1006 malformed fetuses or neonates were identified at abortion or delivery. The prevalence of fetal abnormalities was 3.03%. Fetal anomalies were diagnosed antenatally in 788 (78.33%) cases. Early prenatal diagnosis (before 22 weeks of gestation) was made in 598 (59.44%) cases. The detection of malformed fetuses increased from 19.75% in the first phase of the study (1970-74) to 96.33% in the last phase (1990-91). The specificity of the method was over 99% throughout the study period. The most frequently diagnosed anomalies were urinary tract anomalies (22.86% of cases), followed by head and neck anomalies (18.68%), musculoskeletal anomalies (8.64%), heart anomalies (7.35%) and gastrointestinal anomalies (7.35%). The earliest diagnosed malformations were those of the thoracoabdominal wall (81.08%), followed by defects of the urinary tract (70.86%) and of the diaphragm (70.83%). PMID- 7788492 TI - Development of a training model for ultrasound-guided invasive procedures in fetal medicine. AB - Training in ultrasound-guided procedures in fetal medicine is currently available in a few major fetal medicine units. Unlike elective surgical procedures, cordocentesis is usually performed without sedation as an outpatient procedure and active supervision of the trainee intensifies the anxiety already felt by the patient. In addition, the complication rate is higher in the initial few procedures or when the procedure is not regularly practiced. We have developed a comprehensive method of training for transabdominal invasive procedures using a medical model that simulates the in vivo situation. PMID- 7788493 TI - Doppler studies of the placental and fetal circulation in pregnancies with preterm prelabor amniorrhexis. AB - This study has investigated the effect of intrauterine infection on placental perfusion, fetal circulation and fetal oxygenation in patients with preterm prelabor amniorrhexis. In 69 pregnancies with preterm prelabor amniorrhexis, Doppler ultrasound studies of the uterine and umbilical arteries and the fetal middle cerebral artery and thoracic aorta were performed. Within 1 h after the Doppler studies, cordocentesis and amniocentesis were carried out for microbiological investigations and measurement of blood pO2 and pH. In the amniorrhexis group, there were no significant differences from the appropriate normal mean for gestation in any of the Doppler indices or blood gas results. Furthermore, there were no significant differences between the groups with positive fetal blood or amniotic fluid cultures and those with no evidence of infection. These data demonstrate that, in preterm prelabor amniorrhexis, microbial invasion of the amniotic cavity and fetal bacteremia are not associated with detectable changes in placental perfusion, fetal circulation or fetal oxygenation. PMID- 7788494 TI - Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy. AB - A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788495 TI - Characterization of placenta accreta using transvaginal sonography and color Doppler imaging. AB - The safe use of transvaginal sonography in patients with placenta previa has been confirmed, and has revolutionized precise placental localization. The aim of our study was to evaluate the efficacy of transvaginal sonography and color-coded blood flow in the prediction of placenta accreta. Twenty-one patients with persistent placenta previa were scanned using transvaginal sonography and color coded flow. Suspicion for placenta accreta consisted of total placenta previa at term with several placental lacunae exhibiting marked or turbulent blood flow, as seen with color Doppler transvaginal sonography from within the placenta, extending into the surrounding tissues. Five of the patients exhibited sonographic placental patterns suspicious for placenta accreta and one patient exhibited placental and cervical blood flow described as lacunar. Five Cesarean hysterectomies were performed for placenta accreta. Every placenta accreta was correctly diagnosed sonographically by the use of color flow studies. One patient with suspicion of placenta accreta delivered at another institution, a Cesarean hysterectomy was performed, and the pathology was confirmed. The one placenta previa exhibiting turbulent lacunar flow in the cervical area only was not confirmed to be an accreta at Cesarean section, although hemostasis was difficult at the placental bed. The remaining 15 patients with placenta previa and who on sonography were not suspicious for placenta accreta underwent uncomplicated Cesarean section. Transvaginal sonography and color Doppler imaging improve the diagnostic accuracy in the prediction of placenta accreta in patients with persistent placenta previa. A pattern of turbulent blood flow extending from the placenta into the surrounding tissues should alert the physician to the possibility of placenta accreta. PMID- 7788496 TI - Early fetal endocardial fibroelastosis and critical aortic stenosis: a case report. AB - Endocardial fibroelastosis is characterized by an abnormal thickening of the endocardium of one or both ventricles; the disorder may occur with or without other cardiac anomalies. A diagnosis of endocardial fibroelastosis in utero using fetal echocardiography may be made on the basis of increased echodensity of the endocardium and poor contractility of the ventricle. We describe a case of very early diagnosis of fibroelastosis and aortic valve stenosis observed in utero at 14 weeks' gestation by transvaginal echocardiography. PMID- 7788497 TI - Cerebellar hypoplasia in the second trimester associated with microcephaly at birth. AB - The antenatal diagnosis of microcephaly is most commonly made in the third trimester. Biometric measurements of the head of three or four standard deviations below the mean are suggestive of microcephaly. We report a case of microcephaly where abnormalities in intracerebral architecture, i.e. cerebellar hypoplasia, were noted early in the second trimester. PMID- 7788498 TI - Presentation of the 1994 Ian Donald Gold Medal. PMID- 7788499 TI - LIM domain proteins. AB - The LIM domain is a cysteine-rich domain composed of 2 special zinc fingers that are joined by a 2-amino acid spacer. Some proteins are constituted by LIM domains only while others contain a variety of different functional domains. LIM proteins form a diverse group which includes transcription factors and cytoskeletal proteins. The primary role of LIM domains appears to be in protein-protein interaction, through the formation of dimers with identical or different LIM domains or by binding distinct proteins. In LIM homeodomain proteins, LIM domains seem to function as negative regulatory domains. LIM homeodomain proteins are involved in the control of cell lineage determination and the regulation of differentiation, and LIM-only proteins may have similar roles. LIM-only proteins are also implicated in the control of cell proliferation since several genes encoding such proteins are associated with oncogenic chromosome translocations. In analyzing sequence relationships between LIM domains we suggest that they may be arranged into 5 groups which appear to correlate with the structural and functional properties of the proteins containing these domains. PMID- 7788500 TI - Hammerhead ribozyme: a three dimensional model based on photo-crosslinking data. AB - The hammerhead ribozyme is a small catalytic RNA motif made up of 3 base-paired stems connected by conserved sequences which are essential for catalysis. We have modelled its 3 dimensional structure, taking advantage of proximity data between several substrate and ribozyme residues determined by photo-crosslinking experiments. It is characterized by an Y shape of the 3 stems stabilized in the central core by a network of hydrogen bonds involving in particular 2 non Watson Crick G:A base-pairs. The 5' conserved sequence CUGA makes a sharp turn, the G residue exchanging hydrogen bonds with a conserved base-pair of stem III. The substrate is stretched at the cleavage site. Overall this structure is consistent with that deduced from X-ray crystallography but differences are observed at the level of the CUGA turn. PMID- 7788501 TI - Tat-induced lesions in transgenic mice do not correlate with the HIV-1 LTR transactivation. AB - The product of the tat gene is the most potent transcriptional trans-activator of the HIV-1 LTR (Human Immunodeficiency Virus type 1 Long Terminal Repeat) and might be predicted to be one of the HIV-1 proteins involved in the pathogenesis of AIDS-associated tumors. Deciphering its role in vivo may imply generation of transgenic mouse models displaying different spectra of tat expression. However, it remains difficult to correlate the mRNA expression, the protein production and the eventual pathological consequences in the animal. Our goal in this work was to elaborate a binary transgenic system allowing such an approach, the correlation of the transgene expression in different tissues and the production of the Tat protein, tested as a trans-activator in vivo, with its pathogenic effects. No direct linkage was evident between the degree of transactivation and pathogenesis. Indeed, only benign lesions were observed in malpighian epithelia, where the production of the Tat protein was clearly evidenced by its transactivating property. PMID- 7788502 TI - Ultrastructural localization of cellular prion protein (PrPc) in synaptic boutons of normal hamster hippocampus. AB - The cellular prion protein (PrPc) is a membrane sialoglycoprotein synthesized in the central nervous system and extraneural tissues. Its post-translational modification produces an accumulation of abnormal isoform PrPsc found in brains of transmissible neurodegenerative disorders in animals (scrapie and bovine spongiform encephalopathy) and humans (Kuru, Creutzfeldt-Jakob disease, Gerstmann Straussler-Scheinker syndrome). One major unanswered question relative to PrPc concerns its physiological role in brain neurons, depending largely on the limited knowledge of its subcellular localization. Using a highly-sensitive immunogold electron microscopy technique, we reported that in the hamster dentate gyrus, the synaptic boutons constituted the submicroscopic site where PrPc was observed. This detection was obtained with 2 highly-specific polyclonal antibodies for prion protein. PrPc localization was assigned, both on structural basis and on its co-localization with synaptophysin. The presence of PrPc in synaptic terminals should provide additional informations on its possible role in neuronal transmission and on the implication of synapses in the pathogenesis of spongiform encephalopathies. PMID- 7788503 TI - 7 Alpha-hydroxylation of 27-hydroxycholesterol in rat brain microsomes. AB - 27-hydroxycholesterol is shown to be 7 alpha-hydroxylated by microsomal preparations of rat brain. The apparent Km was about 2 microM and Vmax about 15 pmol/min x mg protein. The reaction might modulate biological functions of 27 hydroxycholesterol, such as its suppressive effect on the activity of 3-hydroxy-3 methylglutaryl-coenzyme A reductase, and supports the possibility of bile acid formation in the brain. PMID- 7788504 TI - Mycobacterial polar glycopeptidolipids enhance resistance to experimental murine candidiasis. AB - Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (pGPL-Mc) greatly increased the resistance of mice against a lethal disseminated Candida albicans infection. This enhanced resistance was demonstrated by an increase in the number of survivors and the prolongation of the mean survival time of animals following a lethal challenge. These effects were dependent upon the infective dose of Candida albicans, the dose of pGPL-Mc and the timing of its administration. This enhanced resistance was correlated with the development and persistence of a hyperleukocytosis, associated with a long lasting increase in the number of polymorphonuclear neutrophils. On the contrary, no candidacidal effect of the serum collected from pretreated mice was observed; suggesting that the ability of pGPL-Mc to increase resistance against Candida albicans infection is likely to be mediated by polymorphonuclear neutrophils. These results confirm previously described immunostimulating properties of pGPL-Mc and open the way for the evaluation of its effect in the prevention of opportunistic infections in neutropenic patients. PMID- 7788505 TI - Activation of human thymocytes induces the phosphorylation of protein tyrosine phosphatase 1C. AB - Phosphorylation of docking proteins is essential for signal transduction. In this report we provide evidence that activation of human thymocytes in culture induces the phosphorylation of the protein tyrosine phosphatase 1C (PTP 1C). Thymocytes were activated with Con A, PMA or Con A+PMA. The enzyme is phosphorylated on its serine and threonine residues. Phosphorylation occurs within 5 min and lasts for 24 h. PTP 1C is phosphorylated by PKC in vivo and in vitro; however, phosphopeptide mapping suggests that in addition to PKC other kinases phosphorylate the enzyme. On the maps of tryptic digests of cultured thymocytes more radiolabeled phosphopeptides are visualized than on the maps of digests of PTP 1C phosphorylated with partially purified PKC alpha or beta. Phosphorylation of PTP 1C decreases its activity, whereas dephosphorylation increases its activity, suggesting that phosphorylation of PTP 1C takes part in the regulation of signal transduction. PMID- 7788506 TI - Cortical memory in Paramecium: a theoretical approach to the structural heredity. AB - Structural heredity is frequently encountered in ciliates. In particular, during division of Paramecium the cortical characteristics of the 2 daughter cells are inherited from those of the mother cell. Genesis of new structures is therefore only possible if there are pre-existing older structures. We attempted to simulate this phenomenon with a model already used to describe the structure and morphogenesis of the cortex of Paramecium. We show that to initiate spatial organization it is enough to choose special starting conditions which comprise the primer of the structure, even if highly localized and at a low concentration of morphogens. This property does not question the basic concepts of genomic heredity. PMID- 7788507 TI - Factors regulating megakaryocyte progenitor commitment to polyploidization. AB - Recognizable megakaryocytes are polyploid cells generated by a clonogenic, diploid progenitor, termed CFU-MKC (colony forming unit, megakaryocyte). In order to quantify polyploidization, ploidy histograms of megakaryocytes determined by microphotometric or flow cytometric measurements of megakaryocyte DNA have generally been used. However these techniques provide no information on the rate of commitment of CFU-MKC to polyploidy. Using a technique of clonal analysis determining the distributions of the number of doublings (NbD) undergone by CFU MKC before committing to polyploidization, the polyploidization probability of CFU-MKC could be derived. This probability was found to be a constant independent from CFU-MKC mitotic history, since NbD distributions are exponential functions characterized by a constant rate of decay per doubling. By studying the effects of growth factors on polyploidization probability, it was also shown that: (1) this parameter is negatively regulated by growth factors contained in poke-weed or WEHI conditioned media, as well as by erythropoietin; (2) commitment to polyploidization does not require prior CFU-MKC division; (3) bipotent erythroid megakaryocyte progenitors have a lower polyploidization probability than CFU-MKC; (4) determination of polyploidization probability reflects the activity of growth factors with greater accuracy than megakaryocyte colony count. PMID- 7788508 TI - Enzymes for enhancing bioremediation of petroleum-contaminated soils: a brief review. AB - During the 1950s and 1960s, hundreds of thousands of underground storage tanks (and above-ground storage tanks) containing petroleum products and hazardous chemicals were installed. Many of these tanks either have been abandoned or have exceeded their useful lives and are leaking, thereby posing a serious threat to the nation's surface and groundwater supplies, as well as to public health. Cleaning up releases of petroleum hydrocarbons or other organic chemicals in the subsurface environment is a real-world problem. Biological treatment of hydrocarbon-contaminated soil is considered to be a relatively low-cost and safe technology; however, its potential for effectively treating recalcitrant wastes has not been fully explored. For millions of years, microorganisms such as bacteria, fungi, actinomycete, protozoa, and others have performed the function of recycling organic matter from which new plant life can grow. This paper examines the biological treatment technology for cleaning up petroleum product contaminated soils, with special emphasis on microbial enzyme systems for enhancing the rate of biodegradation of petroleum hydrocarbons. Classifications and functions of enzymes, as well as the microbes, in degrading the organic contaminants are discussed. In addition, the weathering effect on biodegradation, types of hydrocarbon degraders, advantages associated with enzyme use, methods of enzyme extraction, and future research needs for development and evaluation of enzyme-assisted bioremediation are examined. PMID- 7788509 TI - Effectiveness of smokeless ashtrays. AB - Most environmental tobacco smoke (ETS) issues from the tips of smoldering cigarettes between puffs. Smokeless ashtrays are designed to reduce ETS exposure by removing particulate and/or gas-phase contaminants from this plume. This paper describes an experimental investigation of the effectiveness of four smokeless ashtrays: two commercial devices and two prototypes constructed by the authors. In the basic experimental protocol, one or more cigarettes was permitted to smolder in a room. Particulate or gas-phase pollutant concentrations were measured in the room air over time. Device effectiveness was determined by comparing pollutant concentrations with the device in use to those obtained with no control device. A lung deposition model was applied to further interpret device effectiveness for particle removal. The commercial ashtrays were found to be substantially ineffective in removing ETS particles because of the use of low quality filter media and/or the failure to draw the smoke through the filter. A prototype ashtray using HEPA filter material achieved better than 90% particle removal efficiency. Gas-phase pollutant removal was tested for only one prototype smokeless ashtray, which employed filters containing activated carbon and activated alumina. Removal efficiencies for the 18 gas-phase compounds measured (above the detection limit) were in the range of 70 to 95%. PMID- 7788510 TI - Adverse drug effects and the spectrum of eosinophilic pulmonary disorders. PMID- 7788512 TI - Chronic fatigue in a 43-year-old woman. PMID- 7788511 TI - Bronchial hyperreactivity revisited. AB - OBJECTIVE: The purpose of this article is to review bronchial reactivity: how it is detected, what are the clinical and pathologic correlates and what treatment modulates it. Is it a good diagnostic test for a disease such as asthma? Is it a reasonable parameter to follow in assessing disease severity and response to treatment? DATA SOURCES: Recent studies on human subjects in the English language medical literature involving bronchial hyperreactivity. In particular all studies were sought that correlated indices of inflammation obtained either by bronchoalveolar lavage or biopsy with degree of bronchial hyperresponsiveness. Pertinent studies reviewing disease association with presence of bronchial hyperreactivity were sought. All studies of treatment with inhaled corticosteroids were reviewed and those in which the subjects could be classified as having either mild or moderately severe asthma on the basis of the clinical information given were used to provide data on correlation of bronchial reactivity and disease severity. RESULTS: The relationship of bronchial reactivity and any disease state is not straightforward. It is not clear what causes hyperreactivity of the airways but there must be other factors besides inflammation as bronchial hyperreactivity can occur without microscopic evidence of inflammation. Hyperresponsiveness does not appear to be as sensitive or specific for the diagnosis of asthma as previously thought, or as closely related to the severity of asthma. Effects of treatment appear to be somewhat independent of their impact on bronchial responsiveness. CONCLUSIONS: Airway hyperresponsiveness can be found in many circumstances. Its relationship to symptom production and clinical course in any disease is not clear. Further studies are needed to elucidate the relationship between airways hyperreactivity, asthma, and other lung diseases and the factors that lead to increased bronchial reactivity. PMID- 7788513 TI - Phenytoin-related immunodeficiency associated with Loeffler's syndrome. AB - BACKGROUND: Phenytoin is one of the most commonly prescribed drugs in the United States. Its use is associated with a myriad of adverse reactions, including: eosinophilia, selective IgA deficiency and panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, and interstitial pneumonia. OBJECTIVE: To report a case of immunodeficiency manifest by panhypogammaglobulinemia and a low helper-to-suppressor ratio secondary to phenytoin crossreactivity with phenobarbital and carbamazepine complicated by hepatotoxicity, eosinophilia, and fleeting pulmonary infiltrates. METHODS: Case report; immunoglobulin levels, T and B cell studies, and radiologic evaluation of patient. RESULTS: A 37-year-old Oriental female taking phenytoin and phenobarbital for seizure prophylaxis after resection of a grade IV astrocytoma of the left frontal lobe, developed a rash, elevated liver function tests, and cervical lymphadenopathy with parotid gland enlargement. The abnormalities resolved with discontinuation of the drugs and the patient was discharged on carbamazepine. Eight weeks later the patient was readmitted with fever, slowed mentation, elevated liver function tests, and panhypogammaglobulinemia. Clonazepam was substituted for carbamazepine and the patient subsequently developed a rash and further elevation of her liver function tests. The clonazepam was discontinued and the patient was treated with methylprednisolone. She subsequently developed Loeffler's syndrome and a T cell deficiency with a decreased helper-to-suppressor cell ratio. She was treated with increased doses of methylprednisolone and granulocyte stimulating factor with complete resolution of her symptoms. CONCLUSIONS: Phenytoin is associated with a myriad of side effects, including, rash, eosinophilia, panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, immunosuppression in brain tumor patients, and rarely, pulmonary complications such as Loeffler's syndrome. Cross reactivity with other anticonvulsant agents capable of forming arene oxide intermediates occurs in the cytochrome P-450 system. PMID- 7788515 TI - Major inhalant allergens in Mauritius. AB - BACKGROUND: Bronchial asthma appears to be an important but neglected problem in tropical countries. There is little information about the role of atopy in tropical climates and how atopy is related to asthma there. OBJECTIVE: The present work was aimed at determining the pattern of total serum IgE-titers among a group of patients suffering from asthma in Mauritius. METHOD: Twenty-five asthmatic patients and ten controls who met the criteria for the study were registered. A comprehensive clinical evaluation was followed by allergy skin testing (prick test) to common aeroallergens. Serum total IgE levels were measured in all 35 participants. RESULTS: Of 22 patients studied, 22 had significant levels of IgE when tested to airborne allergens. Positive skin tests against Dermatophagoide pteronyssinus and Dermatophagoide farinae correlated well with the presence of serum total IgE. Sixteen patients also had had moderate to severe exacerbations throughout the year. CONCLUSIONS: The results suggest that house dust mite is an important allergen producing symptoms throughout the year in our patients. PMID- 7788514 TI - Soluble serum interleukin 2 receptors in patients with asthma and allergic bronchopulmonary aspergillosis. AB - BACKGROUND: When T cells are activated, they produce two distinct surface receptors for interleukin 2 (IL2). One of these surface receptors is a 55-kD protein called IL2Ra which is released into peripheral blood following T cell activation. This soluble protein (sIL2R) can be measured in peripheral blood utilizing an ELISA, and thus provides an indirect indicator of T cell activation. OBJECTIVE: The purpose of this study was to determine whether allergic bronchopulmonary aspergillosis (ABPA) was associated with increased soluble interleukin 2 receptors (sIL2R). METHODS: We used the Immunoenzymometric Assay Kit (Immunotech International, Marseille, France) which had a monoclonal antibody to sIL2R to sensitize wells. To determine the degree of T cell activation in patients with asthma and ABPA, we have evaluated the concentration of sIL2R in the peripheral blood in four groups: (1) 26 nonatopic patients, (2) 39 patients skin test positive to Aspergillus who did not have serologic evidence of ABPA, (3) 14 patients with quiescent ABPA, and (4) 13 patients who had a new roentgenographic infiltrate from ABPA. RESULTS: The mean concentration of sIL2R in the four groups were 24.5 pM (+/- 16.7), 38.4 pM (+/- 27.2), 48.4 pM (+/- 28.2), and 64.8 pM (+/- 33.0), respectively. Group 4 was greater than groups 1 and 2 (P < .05), and group 3 was greater than group 1 (P < .05). CONCLUSIONS: In patients with ABPA that is flaring, there is greater T cell activation than in either nonatopic controls or in patients who have asthma. Patients with ABPA in remission also had significantly greater T cell activation than nonatopic controls. PMID- 7788516 TI - Cerebral toxoplasmosis in childhood and adult HIV infection treated with 1-4 hydroxynaphthoquinone and rapid desensitization with pyrimethamine. AB - BACKGROUND: We describe a child and an adult infected with the human immunodeficiency virus (HIV) who developed cerebral lesions consistent with toxoplasmosis. A biopsy in the child and IgG ELISA in both patients confirmed the diagnosis of Toxoplasma gondii. The patients were initially treated with pyrimethamine, however, computerized tomography studies (CT scan) revealed progression of a left frontal and temporoparietal lesion. Therapy in the child was changed to pyrimethamine, clindamycin, and azithromycin. Repeat CT scan showed further disease progression and therapy was changed to high-dose pyrimethamine (3 mg/kg/d) and azithromycin. A subsequent CT scan disclosed further radiologic progression with increasing edema. The adult patient developed a maculopapular rash during attempted treatment with pyrimethamine. METHODS: Introduction of 2 (trans-4[4 chlorophenol] cyclohexy[3-hydroxy-1, 4 naphthoquinone] (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient. RESULTS: HNPQ resulted in resolution of the cerebral lesion in the child and rapid oral desensitization to pyrimethamine produced an excellent clinical response in the adult. To our knowledge, these are the first cases of childhood and adult cerebral toxoplasmosis treated successfully with HNPQ and rapid oral desensitization to pyrimethamine. CONCLUSION: HNPQ and pyrimethamine desensitization should be considered as alternate modes of therapy in patients who become intolerant or fail to respond to traditional therapy for toxoplasmosis. PMID- 7788517 TI - Clinical and immunologic surveys of Hymenoptera hypersensitivity in Japanese forestry workers. AB - BACKGROUND: The increased incidence of bee-sting allergy among beekeepers is well known, whereas Hymenoptera hypersensitivity among forestry workers, who are frequently stung by Hymenoptera, is not well understood. OBJECTIVE: To elucidate the nature of Hymenoptera hypersensitivity among forestry workers and analyze the mechanism involved in Hymenoptera-induced systemic reactions. METHODS: A questionnaire was administered and yellow jacket venom-specific IgE antibody titers measured in 323 forestry workers and 100 age-matched office workers with little occupational exposure to Hymenoptera stings as a control group. RESULTS: From the questionnaire it was found that the percentage of systemic reactions to Hymenoptera stings was significantly greater in the forestry workers than in the control subjects (P < .01). The number of sting exposures was significantly higher in the forestry workers than in the control subjects (P < .01) and was closely correlated with episodes of systemic reaction. Yellow jacket venom specific IgE antibody titers were significantly higher in forestry workers with episodes of systemic reaction compared with those with only local or large local reactions to Hymenoptera (P < .05), although more than half of these subjects had undetectable IgE antibody titers to yellow jacket venom. IgE antibody titers against yellow jacket venom were closely correlated with those of paper wasp (rs = .802, P < .001), which is another frequent source of Hymenoptera stings. In workers with episodes of sting exposure within the most recent 3 years, the period from the last sting was not correlated with yellow jacket venom-specific IgE antibody titers. CONCLUSIONS: The number of sting exposures may contribute to systemic reactions to Hymenoptera sting, and some mechanism other than IgE mediated hypersensitivity may also be involved in Hymenoptera-induced systemic reactions. PMID- 7788518 TI - Nedocromil sodium versus theophylline in the treatment of reversible obstructive airway disease. AB - BACKGROUND: Previous clinical therapeutic research has shown that inhaled nedocromil sodium can replace maintenance oral sustained release theophylline in the management of asthma patients. OBJECTIVE: To compare directly the efficacy and safety of nedocromil sodium and sustained release theophylline. METHODS: Using a randomized, double-blind, double-dummy, parallel-group design, 105 patients with reversible obstructive airways disease (77 asthmatic patients) recruited from four referred-care clinics received, in addition to their existing therapy, 4 mg nedocromil sodium four times daily or sustained release theophylline (maximum daily dose 13 mg/kg) for 6 weeks. Patients with serum theophylline levels within the therapeutic range of 10 to 20 micrograms/mL were retained for efficacy analysis. All were included in a tolerability analysis. Day and nighttime symptoms, inhaled bronchodilator use, morning tightness, cough, and twice daily peak flows were recorded on diary cards. Disease severity, lung function and unusual events were evaluated bi-weekly, and opinion of treatment after 6 weeks. RESULTS: Both treatments improved symptoms, inhaled bronchodilator use and lung function to the same extent. Both treatments were very to moderately effective in > 70% patients. The occurrence of gastrointestinal (P < .05) and central nervous system (P < .01) unusual events was significantly lower for nedocromil sodium compared with theophylline treated patients. CONCLUSIONS: Nedocromil sodium and theophylline were equally effective in this group of patients but nedocromil sodium treatment was associated with significantly fewer side effects, and therefore may be the treatment of choice. PMID- 7788519 TI - Asthma and related atopic disorders in outpatients attending an urban HIV clinic. AB - BACKGROUND: Drug hypersensitivity and pruritic cutaneous disorders are common in human immunodeficiency virus (HIV)-infected patients. Systematic cross-sectional studies, detailing the pattern of atopic disease, however, have not been performed in patients with HIV infection. OBJECTIVE: To analyze the relationships between atopic disease and factors relating to lifestyle, environment, gender, genetics, and HIV disease-associated immune cell depletion. METHODS: CD4 cell counts and interview data were recorded in a survey of 136 adult patients attending a community hospital-based HIV outpatient clinic. The reported presence of various atopic and related conditions (including asthma, hay fever, otitis, sinusitis, and dermatitis) were analyzed for prevalence and associations with CD4 cell depletion, family atopy, and other factors using logistic regression. RESULTS: Seventeen percent and 15% of patients claimed to have asthma and hay fever, respectively. Eleven percent claimed chronic nasal symptoms without known hay fever. A recent CD4 count > or = 200 cells/dL was significantly associated with current asthma (P = .01) and this association remained after adjusting for other significant factors. The mean recent log CD4 count for patients with current asthma was significantly higher than other patients (5.63 +/- .73 versus 4.92 +/- 1.38, P = .001). There was no association between rhinitis and CD4 cell depletion. Histories of recent sinusitis (24%) and ear infections (16%) were common, and were significantly associated with current hay fever +/- chronic nasal symptoms (P < .05). Chronic pruritic rashes or eczema were reported in 29% and were more frequent in those with CD4 counts < 200/dL. Family histories of either asthma or hay fever were significantly associated with several condition including hay fever +/- chronic nasal symptoms, otitis, drug allergy, chronic pruritic rashes or eczema, and asthma. CONCLUSIONS: Although atopic disorders in the setting of HIV infection appear to have some clinical associations similar to that reported for the general population, asthma appears to have a predilection towards less severe CD4 cell depletion. The potential role of chronic rhinitis +/ family atopy as risk factors for sinusitis and otitis may be important because treatment of selected individuals with rhinitis may potentially decrease some paranasal disease-related morbidity in HIV infection. PMID- 7788520 TI - Spontaneous variations in congestion of the nasal mucosa. AB - BACKGROUND: Nasal patency shows spontaneous variations but is also influenced by exercise and allergic conditions. These variations have not been described in detail with regard to allergy. OBJECTIVES: The purpose of this study was to examine whether these variations are different in nonallergic subjects and in subjects with nasal allergy to pollen out of the pollen season. METHODS: We examined 12 of each type of subject in the winter on two days for seven hours in a climatic chamber with constant temperature and relative humidity, one day for examination of spontaneous variations and one day for examination of exercise response. Every 15 minutes the volume of the nasal cavities, minimum cross sectional areas, and areas at fixed distances from the nostril were measured by acoustic rhinometry. Symptoms were scored by a questionnaire. RESULTS: There were more pronounced spontaneous variations expressed as the coefficient of variation of nasal volume in allergic than in nonallergic subjects (14% against 9%, P = .004). A nasal cycle was observed in four of the nonallergic subjects and three of the allergic subjects. In the postexercise period, the spontaneous variations in the nonallergic subjects were increased but decreased in the allergic subjects. Exercise increased nasal patency more in the allergic subjects but only significantly for the cross-sectional area at 3.3 cm (105% compared with 43% in the nonallergic subjects, P = .05). In contrast, pharmacologic decongestion in the allergic subjects showed a tendency to be more pronounced for the nasal cavity volume (55% increase versus 42%, P = .08). There was no difference between the groups in nasal symptom scores. CONCLUSION: Allergic subjects out of the pollen season have more congested and more sensitive nasal mucosa than nonallergic subjects. PMID- 7788521 TI - Onychomycosis, Trichophyton allergy and asthma--a causal relationship? PMID- 7788522 TI - 4th European Symposium on the Application of Saliva in Clinical Practice and Research. Berlin, March 22-24, 1995. Abstracts. PMID- 7788523 TI - Cloning and identification of the hemG gene encoding protoporphyrinogen oxidase (PPO) of Escherichia coli K-12. AB - Cells of the VSR751 strain, which was previously isolated as a photoresistant revertant of the visA-deleted (hemH-deleted) strain of Escherichia coli K-12, accumulated uroporphyrin (uro), coproporphyrin (copro) and protoporphyrin IX (proto), but did not accumulate as much protoporphyrin as cells of the parental strain (hemH-deleted). Therefore, we concluded that strain VSR751 must be defective in protoporphyrinogen oxidase (PPO), the product of the hemG gene. By complementation analysis using VSR751, we isolated and identified this gene. The hemG gene is located at 86 mim on the E. coli chromosome, just upstream of the rrnA operon, and is transcribed clockwise in the same direction as the rrnA operon. This gene encodes a 181-amino acid protein with a calculated molecular mass of about 21 kDa. Sequence analysis revealed the presence of flavodoxin motif, suggesting tha a cofactor of this enzyme is flavin mononucleotide, which is consistent with the previous report that the mammalian PPO had the flavin cofactor. PMID- 7788525 TI - cDNA sequences of three kinds of beta-tubulins from rice. AB - Complete nucleotide sequences of three kinds of rice beta-tubulin cDNA clones (pTUB22, R1623 and R2242) were determined. Southern hybridization indicated that these beta-tubulins consist of one gene family. Using RFLP mapping, these three beta-tubulin cDNAs were mapped to different chromosomes indicating at least three loci for the beta-tubulin gene. The deduced amino acid sequences of these cDNAs showed a high similarity to other plant beta-tubulins. The asparagine residue located at the 100th amino acid from the N-terminus of plant beta-tubulins was also conserved with these three beta-tubulins. This asparagine is thought to be responsible for the sensitivity against rhizoxin, the toxin of the pathogen of rice seedling blight, Rhizopus sp. a soil-borne microorganism. Expression of the three beta-tubulin genes was analyzed by Northern blotting and all three clones were expressed in root, the possible target tissue of rhizoxin. These results suggest that these clones are candidates of beta-tubulins targeted by rhizoxin. PMID- 7788524 TI - Cloning and sequencing of sulfite reductase alpha subunit gene from Saccharomyces cerevisiae. AB - A DNA fragment of 2.1 kb was specifically amplified by PCR with primers based on the amino acid sequences obtained from the N-terminal region and the cyanogen bromide-derived peptide of the sulfite reductase alpha subunit in Saccharomyces cerevisiae. With this fragment as a probe, the gene coding for the sulfite reductase alpha subunit was isolated from a genomic library of S. cerevisiae. Sequencing analysis revealed that the gene contains a 3105-bp open reading frame, which is large enough to code for a protein of 1035 amino acid residues. The transcript of the sulfite reductase alpha subunit gene was detected by Northern analysis after methionine deprivation, but the amount of the transcript did not directly correlate with the enzyme activity. The DNA fragment containing the sulfite reductase alpha subunit gene rescued the met10 phenotype by complementation. PMID- 7788526 TI - Comparative analysis of mouse NotI linking clones with mouse and human genomic sequences and transcripts. AB - NotI cleavage sites are frequently associated with CpG islands that identify the 5' regulatory sites of functional genes in the genome. Therefore we analyzed a sample of 22 NotI linking clones prepared from mouse brain DNA, to determine whether these mouse NotI site associated clones could be used for comparative analysis of mouse and human genomes by cross-reaction with both mouse and human genomic DNA and RNA in Southern and Northern hybridization. We further examined whether we could establish the identity of these clones with known genes by comparing the nucleotide sequences surrounding the NotI site with the GenBank database. We observed that 70% of the clones cross-hybridized with human DNA and that 4 of 11 tested clones (36%) detected a transcript in human HeLa cells RNA whereas 73% clones (8/11) detected transcripts in mouse RNAs from one or more organs. Single pass sequence analysis was successful on 16 of 19 clones. The GC content in these sequence was very high (48.8% to 73.8%) suggesting that 12 of 16 sequenced clones contained a CpG island. Three out of 19 clones showed significant similarity with previously analyzed mouse gene sequences in GenBank, including the mouse rRNA gene family, cathepsin and the scip POU-domain genes. In addition, two sequences showed significant similarity to the human and rabbit protein phosphatase 2A-beta subunit and the human transforming growth factor beta. Thus, 5 of 16 clones showed homology with identified genes. These results and the recent work of using RLGS methods for genetic mapping indicate that NotI linking clones can be used to efficiently cross reference a comparative analysis of the mouse and human genomic maps. PMID- 7788527 TI - Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. AB - We isolated full-length cDNA clones from size-fractionated cDNA libraries of human immature myeloid cell line KG-1, and the coding sequences of 40 genes were newly predicted. A computer search of the GenBank/EMBL databases indicated that the sequences of 14 genes were unrelated to any reported genes, while the remaining 26 genes carried some sequences with similarities to known genes. Significant transmembrane domains were identified in 17 genes, and protein motifs that matched those in the PROSITE motif database were identified in 11 genes. Northern hybridization analysis with 18 different cells and tissues demonstrated that 10 genes were apparently expressed in a cell-specific or tissue-specific manner. Among the genes predicted, half were isolated from the medium-sized cDNA library and the other half from the small-sized cDNA library, and their average sizes were 4 kb and 1.4 kb, respectively. As judged by Northern hybridization profiles, small-sized cDNAs appeared to be expressed more ubiquitously and abundantly in various tissues, compared with that of medium-sized cDNAs. PMID- 7788528 TI - Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA. AB - We cloned and sequenced the cDNAs which code for rat cellular nucleic acid binding protein (CNBP). In-frame insertion/deletion differences were found among the clones at two sites in the open reading frame, suggesting alternative splicing of the message or the presence of multiple genes which code for this protein. The deduced amino acid sequence revealed that one rat CNBP sequence was completely identical to its human counterpart. This striking conservation, together with the fact that homologous genes have been found in various organisms including Schizosaccharomyces pombe, suggests that CNBP plays a basic biological role in eukaryotic cells. The recombinant GST-CNBP fusion protein produced in Escherichia coli bound to a G-rich single-stranded RNA and DNA in a sequence specific manner. PMID- 7788529 TI - Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1 (supplement). PMID- 7788530 TI - In vitro processing of heteroduplex loops and mismatches by endonuclease VII. AB - Endonuclease VII is a Holliday-structure resolving enzyme of phage T4 which cleaves at junctions of branched DNAs and at mispairings. In extension of these findings we report the following: i) Endonuclease VII can discriminate between a large heteroduplex loop and a TT mismatch arranged in tandem, 6 nt distant from each other, in the same heteroduplex molecule. The enzyme cleaves two nucleotides 3' from the base of the loop or the TT mismatch. ii) Similar to its reactions with mismatches cleavage of heteroduplex loops by endonucleave VII can also initiate correction of perfect double-strandedness by T4 DNA polymerase and T4 DNA-ligase in vitro. Loops of 8 nt and 20 nt were repaired efficiently. iii) For the first time endonuclease VII cleavage sites were also mapped in single stranded DNA if it was part of the 20-nt loop. This suggests that looping of single-stranded DNA can induce formation of secondary structures, which are recognizable by endonuclease VII. PMID- 7788531 TI - The abdomen as source of sepsis in critically ill patients. AB - Among patients with life-threatening sepsis that has no clear site of origin, the abdomen continues to be a probable and tractable possibility. The cavity has the microbiologic and anatomic potential for sudden or indolent sepsis and the cause may be either obvious or obscure. The abdomen or the various structures may be primary sources that are secondary and independent of disease that brought the patient to peril. They also could be secondary and dependent upon an abdominal operation complicated by sepsis. The partnership of intensivist and surgical consultant, addressing possibilities and challenges, must identify the most probable cause and the most timely response for positive intervention in the critically ill patient threatened by sepsis. PMID- 7788532 TI - Biliary tract emergencies. Endoscopic and medical management. AB - The application of therapeutic ERCP and interventional radiology has significantly altered the treatment of biliary tract emergencies. Although surgery is the principal treatment for acute cholecystitis, nonoperative alternatives exist for high-risk patients. New, prospective, randomized trials have demonstrated that endoscopic management of severe cholangitis is superior to surgery, and that endoscopic sphincterotomy and stone extraction are superior to conservative treatment in severe gallstone pancreatitis. ERCP allows nonoperative management of postoperative bile leaks as well. PMID- 7788533 TI - Acute pancreatitis. Medical management. AB - The medical management of acute pancreatitis is primarily supportive and involves making the patient nulla per os, providing adequate intravenous hydration, and controlling pain with analgesics. Systems to identify patients with severe pancreatitis at risk for morbidity and mortality are available but require supplementation with frequent, experienced clinical observation. A number of modalities to inhibit pancreatic secretion or pancreatic proteases have not been successful in clinical trials, although larger studies in patients with more severe pancreatitis are required to ultimately assess their effectiveness. The empiric use of imipenem and long-term peritoneal lavage in patients with severe or necrotizing pancreatitis appear promising but further studies are needed. The removal of impacted gallstones in patients with severe pancreatitis or cholangitis is useful, provided an expert endoscopist is available. Improvements in our ability to document pancreatic infection early by CT-directed aspiration have markedly improved our ability to manage pancreatic infection. PMID- 7788534 TI - Acute pancreatitis. Surgical management. AB - In general, the best approach to pancreatitis is to recognize its presence early, resuscitate the patient aggressively, and employ nutritional and medical therapy to avoid complications. Nonetheless, either because of trauma or failure of medical therapy, some patients develop complications (e.g., hemorrhagic or necrotizing pancreatitis, abscess, pseudocyst, or fistula) that require operative intervention. Expert surgical judgment is required to decide which patients require surgery, when to operate, and what operation(s) to perform. Many of these patients require multiple surgical procedures and are critically ill, requiring careful attention to nutritional support, ventilatory management, and surveillance for sepsis. The care of these patients requires a multidisciplinary approach involving personnel in internal medicine, gastroenterology, radiology, surgery, anesthesiology, and nursing. Pancreatitis does not respect the boundaries of class, race, creed, gender, or traditional specialty interests; only by using a collegial approach, which shares expertise in a multidisciplinary fashion, is it possible to optimize patient care and salvage critically ill patients with this deadly disease. PMID- 7788535 TI - Stress-related mucosal disease. Pathophysiology, prevention, and treatment. AB - The advent of gastrointestinal endoscopy has allowed us to follow the morphologic results of severe stress on the gastrointestinal mucosa. It has become clear, however, that the presence of mucosal abnormalities does not always correlate with the presence of overt bleeding, or with the effect of bleeding on the overall outcome of such patients. In fact, the incidence of severe gastrointestinal hemorrhage, secondary to stress-related mucosal disease, has been decreasing over the past decade, as the care of these critically ill patients has improved. In patients who do have overt hemorrhage, however, the mortality rate is extremely high. It therefore remains the duty of the clinician to identify patients who are at high risk of having overt hemorrhage, and ensure that they receive adequate prophylactic therapy. PMID- 7788536 TI - The critical care management of nonvariceal upper gastrointestinal bleeding. AB - Upper gastrointestinal hemorrhage, although accounting for more than 300,000 annual hospital admissions in the United States, continued to have about a 10% mortality rate over the past 50 years. Whether this is secondary to the increasing age of patients admitted with UGI hemorrhage, and their comorbid diseases, is unknown. The major approach to these patients includes volume and cardiovascular resuscitation, as well as surgical and gastroenterology consultation. Both clinical signs and endoscopic features in patients aid in predicting those at high risk of either rebleeding or dying, allowing for more aggressive steps, including endoscopic therapy of the bleeding site and surgery. Improved intensive care measures and endoscopic therapies for these patients may account for the signs of a recent decline in this mortality rate during the past 10 years. PMID- 7788537 TI - Lower intestinal hemorrhage. AB - Lower intestinal hemorrhage, defined as bleeding originating below the ligament of Treitz, is a common clinical problem frequently requiring hospital admission. The two chief causes, vascular ectasia and diverticulosis, are degenerative diseases usually found in the elderly. This article focuses on those disease entities that potentially can result in significant lower intestinal blood loss. It also discusses a generalized approach to the diagnostic evaluation leading to specific management of the patient presenting with this problem. PMID- 7788538 TI - Variceal hemorrhage. AB - Variceal hemorrhage is a complication of portal hypertension that has high mortality and high recurrence rates. Management of variceal bleeding involves three areas: treatment of active hemorrhage, prevention of rebleeding, and prevention of first variceal bleeding. There are two main therapeutic avenues: methods directed at reducing portal pressure, such as pharmacologic therapy, shunt surgery, and TIPS; and methods that act locally by decreasing or interrupting blood flow through a specific varice, such as sclerotherapy, banding, and balloon tamponade. The relative effectiveness of each of these interventions is discussed in this article. PMID- 7788539 TI - Fulminant hepatic failure. AB - Fulminant hepatic failure is a devastating complication of viral hepatitis, hepatotoxic exposures, and a variety of other acute liver diseases. Although this syndrome is associated with high mortality, liver transplantation can be life saving. This article discusses the medical management of fulminant hepatic failure and emphasizes complications, determinants of survival, and patient selection for liver transplantation. PMID- 7788540 TI - Complications of chronic liver disease. AB - The patient with advanced cirrhosis presents unique challenges to the critical care physician, in great measure because of the protean functions attributable to the liver and the multiplicity of derangements that may occur. Portal hypertension, once it develops, is the source of potentially devastating complications that include life-threatening hemorrhage, infection, renal failure, and coma. Parenchymal disease can result in coagulopathy as well as altered handling of both endogenous (hormones, metabolites) and exogenous (drugs) substances. Cirrhosis also can be complicated by the development of HCC, which may worsen portal hypertension, deplete parenchymal reserves, and result in catastrophic complications. The prospect of cure by liver transplantation in selected cases serves to underscore the importance of prompt and vigilant management of patients with decompensated cirrhosis in the critical care setting. PMID- 7788541 TI - Diarrhea in the intensive care patient. AB - Approximately one third of patients admitted to the ICU develop diarrhea during their hospitalization. Diarrhea can lead to further complications, such as volume depletion and wound infection, and can significantly increase medical costs. The most common causative factors are medications, enteral feedings, and C. difficile infections. These may be implicated alone or in combination. Further investigations of the pathophysiology of ICU diarrhea as well as potential therapies are needed to clarify the proper approach to this important and complex problem. PMID- 7788543 TI - Emergencies in inflammatory bowel disease. AB - Ulcerative colitis and Crohn's disease, the principal IBDs, are characterized most often by a chronic relapsing course. Despite the protracted nature of these disorders they can present in an acute manner as gastrointestinal emergencies. The urgent manifestations include both intestinal and extraintestinal disease. Extraintestinal emergencies can be ocular, rheumatologic, hematologic, and urologic. Intestinal emergencies often are more severe and can be life threatening. These may include obstruction, abscesses, perforation, and hemorrhage. The successful management of such complications depends on early diagnosis and the judicious and timely use of both medical and surgical therapies. PMID- 7788542 TI - Acute mesenteric ischemia. AB - The term acute mesenteric ischemia (AMI) is applied to a wide spectrum of bowel injury within the distribution of the superior mesenteric vessels, ranging from reversible alterations in bowel function to transmural necrosis of the bowel wall. Intensivists not only are called upon to manage this catastrophic disease but also may be faced with AMI as a consequence of other illnesses that they treat. PMID- 7788544 TI - Gastrointestinal emergencies in the patient with AIDS. AB - The clinical importance of gastrointestinal disorders among patients with acquired immunodeficiency syndrome (AIDS) is enormous. Estimates of gastrointestinal complaints among AIDS patients range from 30% to 90%. Many of these patients may be chronically ill and have multiple simultaneous opportunistic pathogens and neoplasms. The diagnosis and management of serious gastrointestinal complications that often occur in the setting of chronic illness represent major challenges in the care of patients with AIDS. PMID- 7788545 TI - [Molecular biology and clinical nephrology]. PMID- 7788546 TI - [Different expressions of alpha 2 (IV) and alpha 3 (IV) collagen mRNAs in renal glomeruli of IgA nephropathy]. AB - The levels of extracellular matrix protein mRNAs were increased prior to the appearance of histological glomerulosclerosis in isolated glomeruli from several animal models. Striker studied renal biopsies (Seminar in Nephrology, 13:508,1993). We made a comparable study in human renal biopsies to assess the levels of glomerular alpha 2 (IV) and alpha 3 (IV) collagen gene expressions in renal biopsies. Renal biopsy specimens were obtained from 11 patients (7 IgA nephropathy and 4 mesangial proliferative glomerulonephritis). Glomerular lesion was divided into 5 grades. The amount of collagen type IV in glomerular matrix was evaluated by immunoperoxidase staining using a monoclonal antibody to type IV collagen. For gene expression analysis, glomeruli were dissected out from about 10% of each biopsy specimen. The expressions of alpha 2 (IV) and alpha 3 (IV) collagen mRNAs were analyzed by using in situ reverse transcription coupled with polymerase chain reaction. Each PCR reaction contained an amount of cDNA template equivalent to that obtained from 1/10 of a glomerulus, alpha 2 (IV) and alpha 3 (IV) collagen mRNAs were detected in all specimens. All 3 cases of IgAN with grade III glomerular lesion had a more marked increment of glomerular alpha 2 (IV) collagen cDNA than that of the other 3 IgAN patients with grade II lesion (the intensity of PCR product, grade III 0.54 +/- 0.12, VS grade II 0.25 +/- 0.08, P < 0.05). No discrepancies were detected in the level of glomerular alpha 3 (IV) collagen cDNA and the intensity of collagen IV staining between these two groups of IgAN. Interestingly, in MsPGN patients there was no difference in the expression of glomerular alpha 2 (IV) collagen mRNA between grade II and grade III glomerular lesions. The results suggested that the detection of glomerular alpha 2 (IV) collagen mRNA level in IgAN patients may help to define the pathological classification. PMID- 7788547 TI - [In situ expression of intercellular adhesion molecule-1 in human glomerulonephritis]. AB - We conducted immunocytochemical analysis with in situ hybridization technique to investigate the presence and role of intercellular adhesion molecule-1 (ICAM-1) in normal and diseased kidneys. A total of 64 renal biopsy specimens were classified in three groups according to the degree of cellular proliferation in glomerulus. Group A presented no or mild proliferation (n = 38). Group B showed definite proliferation (n = 21). Group C had glomerular sclerosis (n = 5). The ratio of cases exhibiting increased glomerular ICAM-1 expression in lupus nephritis (9/10) was significantly different from that in minimally changed disease (1/5) (P = 0.017). Glomerular ICAM-1 expression level correlated well with the cellular proliferation and infiltration in glomerulus (B&A: P < 0.001; C&B: P < 0.05). The percentage of cases with tubular ICAM-1 positivity in group B (81.0%) and group C (100%) was greater than that in group A (52.6%), which was also correlated with that of interstitial cell infiltration. In situ hybridization of 9 renal biopsies with digoxigenin labelled oligo probe proved immunocytochemical findings. We conclude that glomerular ICAM-1 expression level is correlated with inflammatory degree of glomerulus and that tubular ICAM-1 expression is associated with interstitial cell infiltration. PMID- 7788548 TI - [Image analysis for intercellular adhesion molecule-1 expression in MRI/lpr mice: effects of Chinese herb medicine]. AB - To clarify the role of intercellular adhesion molecule-1 (ICAM-1) on pathogenesis of autoimmune lupus nephritis in MRL/lpr mice and the effects of Chinese herb medicine (stragalin), a computer image analysis system was used to study immunodepositions of ICAM-1, immunoglobulins and C3 in renal tissue sections of the mice. ICAM-1 was found in the mesangial area and deposited along the glomerular capillary walls in MRL/lpr mice. The distribution intensity of ICAM-1, immunoglobulins and C3 were significantly decreased after treatment with stragalin in form of decoction per os in the mice. We found that ICAM-1 might play an important role in pathogenesis of autoimmune lupus nephritis in MRL/lpr mice and Chinese herb medicine has some inhibition effects on immunodepositions in renal tissue of MRL/lpr mice. PMID- 7788549 TI - [Inhibition of growth factor stimulation of mitogen-activated protein kinase by prostaglandin E2 in rat renal mesangial cells]. AB - Activation of the mitogen-activated protein kinase (MAPK) pathway is believed to play a critical role in normal and pathophysiologic proliferation of mesangial cells. Recent studies have shown that MAP kinase activation by growth factors in other cell types involves activation of the low molecular weight G-protein ras and the protooncogene serine kinase c-raf-1. In this study the role of this pathway in rat renal mesangial cells was assessed. 20ng/ml of platelet-derived growth factor (PDGF), 10(-8) mol/L epidermal growth factor (EGF) as well as phorbol ester (10(-6) mol/L PMA) rapidly activated MAP kinase by 3-4 fold in these cells. PDGF and EGF, but not PMA were able to activate c-raf-1 and ras activity. Stimulation with inflammatory mediator PGE2 (50 mumol/L) or elevation of Intracellular cAMP by treatment of cells with forskolin (25 mumol/L) markedly blunted activation of MAP kinase induced by PDGF and EGF, but not PMA. Consistent with this observation, PGE2 abolished growth factor induced activation of c-raf 1. However, ras activation induced by growth factor was not affected by PGE2 and forskolin. These results suggest that MAP kinase activation can occur by at least two separate pathways in mesangial cells. Tyrosine kinase receptors activate MAP kinase through activation of ras and raf. This pathway can be blocked by PGE2 and elevation of cAMP, presumably by interfering with the ability of ras to activate raf. In addition, activation of protein kinase C by phorbol esters can activate MAP kinase in a ras/raf-independent manner. This pathway is not sensitive to inhibition by PGE2 or cAMP. It is likely that activation of each of these pathways, both resulting in a stimulated MAP kinase, will have different physiologic consequences in mediating mesangial cells growth. PMID- 7788550 TI - [Expression and loss of heterozygosity of DCC gene in human lung cancer]. AB - The level of DCC mRNA expression was evaluated in tissue specimens from lung cancer patients by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis. Obvious reduction of DCC gene expression was observed in 4 of 7 specimens (55%). In two specimens DCC transcript could only be detected after Southern blot hybridization of RT-PCR product. The average level of DCC expression in cancer tissue was about 45% of normal tissue as estimated by laser densitometer. We also studied DNA samples for loss of heterozygosity (LOH) at DCC locus at two polymorphic sites. Among the 15 specimens including 7 samples for RT-PCR, 9 (60%) were informative at either of two polymorphic sites. LOH was observed in 5 (55%). Two at the MspI-RFLP (restriction fragment length polymorphism) site and 3 at the site of VNTR (variable number of tandem repeat). These results suggest that allele loss and decreased expression of DCC gene are frequent events and the possible involvement of DCC gene in the pathogenesis of human lung cancer. PMID- 7788552 TI - [Experimental study on in vivo hematopoietic regulation of interleukin-6 gene therapy]. AB - Interleukin-6 (IL-6), a pleiotropic cytokine, is involved in extensive immune regulation and hematopoietic regulation. We observed the effect of fibroblast mediated human IL-6 gene therapy on hematopoiesis. The platelet counts started to increase at day 4 after implantation of IL-6 highly secreting fibroblast cells and peaked at day 10 and lasted at high level for 22 days. The neutrophil counts were elevated after their implantation, but WBC did not show any remarkable increase. The CFU-GM and CFU-MK in bone marrow and spleen were also increased significantly. The results demonstrated that fibroblasts mediated human IL-6 gene therapy can significantly augment in vivo hematopoietic functions in bone marrow and spleen and elevate the number of nuetrophils and platelets. This study provides a new approach to treat thrombopenia and chemotherapy or radiotherapy induced hematopoietic suppression. PMID- 7788551 TI - [Detection of c-myc translocation in human lung cancer cells by fluorescence in situ hybridization (FISH)]. AB - c-myc gene amplification has been found in lung cancer, however, it can not explain all cases of lung cancer with c-myc gene overexpression. Gene translocation is one of the ways by which oncogene is activated. But the old methods for detecting gene mutations are not so effective for the detection of gene translocation, especially in solid tumors. Fluorescence in situ hybridization (FISH) can be used to detect gene translocation more efficiently. Using FISH, we discovered c-myc gene translocation in a lung adenocarcinoma cell line GLC-82 and SV40T-transformed human bronchial epithelial cells. In GLC-82, c myc gene translocated to the short arm of a C group marker chromosome. In the SV40T-transformed epithelial cells, c-myc gene translocated to 14q32, which was the same as that found in Burkitt's lymphomas. Translocation was related to oncogene activation. c-myc translocation may play an important role in the carcinogenesis of lung cancer. PMID- 7788553 TI - [Clinicopathologic characteristics of primary liver cancer in patients younger than 35 years]. AB - To investigate clinicopathologic characteristics of primary liver cancer (PLC) in young adults, 77 patients younger than 35 years were compared with 603 patients older than 35 years during the same period. In the young patients, PLC showed a low incidence of PLC detected at mass survey (young 15.6% versus older 28.7%, P < 0.05); a low incidence of hepatitis history (young 36.8% versus older 66.3%, P < 0.01); a high incidence of positive hepatitis B virus surface antigen (HBsAg) (young 79.2% versus older 67.6%, P < 0.05); a low incidence of associated cirrhosis (young 64.9% versus older 90.7%, P < 0.01); larger tumor size (PLC > 5cm; young 87.0% versus older 73.0%, P < 0.01); a more advanced stage of the disease in TNM classification (stage III; young 29.9% versus older 18.2%, P < 0.05). It is suggested that hepatitis B virus (HBV) may play an important role in the development of PLC without associated liver cirrhosis in the young patients. A close periodic surveillance of young adults with a positive HBsAg is important to detect PLC at an early stage. PMID- 7788555 TI - [Affection of growth of zinc deficiency growing rats]. AB - Fifty male Sprague-Dawley rats with an average live mass of 42 +/- 4g were divided into 5 groups of 10 animals each. An artificial semi-systhesis diet was given to the animals. Group 1 received a control diet (32.2 mg Zn/kg DM), and group 2 a zinc deficient diet (3.4 mg Zn/kg DM) ad libitum. The animals of group 3 were pair fed to group 2 with a diet (84.9 mg Zn/KgDM). Diets of group 4 and 5 contained zinc (4.4 and 5.5 kg Zn/micrograms DM), respectively. The two groups also pair fed to group 2. The food intake and live mass gain were observed every day. After 26 days of experiment, the animals were decapitated; the blood samples were collected for the analysis of serum zinc, zinc binding capacity, and alkaline phosphatase. PMID- 7788554 TI - [Hemofiltration ameliorating reperfusion injury after complete cerebral ischemia: an experimental study]. AB - The effects of hemofiltration on cerebral resuscitation were studied by using resuscitation model of potassemia-induced cardiac arrest and cardiopulmonary bypass. Sixteen rabbits were divided into control group (CG) and hemofiltration group (HFG). Blood lactic acid, lipid peroxidant (LPO), serum iron, middle molecular substance (MMS) were determined. Neurologic deficit score (NDS) system was used to evaluate neurologic function. The level of blood lactic acid was increased in both CG and HFG. It was higher in CG than in HFG (P > 0.05). Serum iron was increased in CG, however, it was decreased in HFG. The difference between the two groups was significant (P < 0.01). LPO was increased significantly in CG and there was no obvious changes in HFG. MMS was increased gradually during reperfusion in CG, whereas it was decreased in HFG. There was significant difference in the corresponding times of the two groups. NDS of CG was higher than that of HFG (32 +/- 12 vs 18 +/- 10) (P < 0.01). These data demonstrate that hemofiltration is able to eliminate ischemic and reperfusional toxic products quickly. Additionally, free iron, agonist factor of catalyzing free radical reaction, does not increase because free radicals and lactic acid are eliminated quickly, inhibiting free radical tissue injury and improving cerebral resuscitation. PMID- 7788556 TI - [Advance in the research of promotive effects of growth factors on the repair of acute kidney tubular injuries]. PMID- 7788558 TI - Determination of carbonic anhydrase-III by enzyme-immunoassay in liver, muscle and serum of male rats with streptozotocin-induced diabetes mellitus. AB - Insulin has a plethora of metabolic effects but its action on carbonic anhydrase III (CA-III), a key enzyme in acid-base regulation, has been little studied. The present studies examined the effects of streptozotocin induced diabetes on the concentrations of CA-III. The concentration of CA-III in the liver, muscles and serum of rats with experimental diabetes mellitus was measured by the method of enzyme-immunoassay. Streptozotocin-induced diabetes mellitus resulted in a reduction in concentration of CA-III in the liver and serum, but not in skeletal muscles, of adult male rats. A 98% reduction in hepatic CA-III content relative to control values was observed. The reduction in CA-III content in the liver was restored to control value by administration of insulin. The CA-III content in serum of diabetic rats declined to approx. 25% of control values, but the reduction was unaffected by administration of insulin. The concentration of CA III in the liver and serum of diabetic rats was not influenced by administration of methyltestosterone. Although the content of CA-III in m. rectus femoris, m. tibialis craniaris and m. soleus differed, no significant difference of CA-III content was found between diabetes mellitus and control rats. The effect of chronic diabetes mellitus on CA-III content was obviously different between liver and muscle, suggesting that the regulation of CA-III biosynthesis differs between these two tissues. These results suggest that biosynthesis of CA-III in hepatocytes of rats is influenced by irregular patterns of GH secretion brought about by diabetes mellitus. PMID- 7788557 TI - Absorption spectroscopy of the complexation between superpotent guanidinium sweeteners and specific monoclonal antibodies. AB - Spectroscopic studies of antibody-antigen interactions can provide useful information about the interactive motifs and energetics involved in the intermolecular association process. In this study we used absorption spectroscopy to examine the interactions between five different monoclonal antibodies (mAb) and four superpotent ligand sweeteners. Quantitative changes in the absorption spectra in the wavelength range of 230-800 nm were utilized for the determination of intrinsic association constants and thermodynamic parameters of the mAb-ligand complexes. The intrinsic association constants for the mAb-ligand complexes were found to be in the range of 10(7)-10(5) lM-1 and were in agreement with previous radioimmunoassay determinations. For two mAb, qualitative changes in the spectra in the 340 nm range could be identified and were related to the presence of charge-transfer interaction between the guanidinium ligand and aromatic residues in the binding site of the mAb. A charge transfer spectra was observed in mAb NC10.8 with two different sweetener ligands. The thermodynamic parameters of the ligand-mAb interactions were analyzed by van't Hoff plots and in almost all cases the reactions were found to be enthalpically driven. The determinations of intrinsic affinity and thermodynamic parameters may be useful in computer-aided molecular modelling studies of the antibody binding pocket and predicted ligand docking orientations. Antibody NC6.8 was found to react with this set of sweetener ligands in a rank order that is related to their sweetness potencies and the spectroscopic findings for NC6.8 are in agreement with the X-ray diffraction data of the Fab-ligand crystal structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788559 TI - Brain mRNA from infants of aluminium-exposed lactating rabbits. AB - The neurotoxicity of aluminium (Al) involves bundling of neurofilaments, increased chromatin binding and decreased protein synthesis in Al injected rabbits. Thus, using an amphipathic Al ligand, maltol, experiments were carried out to examine whether or not administration of Al to lactating mother rabbits reduces brain protein synthesis in their offspring. Lactating mother rabbits received s.c. injections 3 times weekly of aluminium (Al) maltolate (1 mg Al/kg body wt) or an equivalent weight of maltol, for 4 weeks post-partum. Polysome preparations were obtained from the brain of their infants in order to assess mRNA translation in cell-free protein synthesizing systems. The brain polysomes showed a statistically significant reduction in the incorporation of [14C]leucine into protein. The poly (A)+ and poly (A)- fractions obtained from these polysomes showed reductions of 44% or more in the incorporation of [35S]methionine into protein. A variety of products separated by SDS-polyacrylamide gel electrophoresis all exhibited decreased labelling. These experiments suggest that infant rabbits exposed to a highly neurotoxic form of Al in milk exhibit changes in brain protein synthesis which resemble those in infants injected directly with Al. PMID- 7788560 TI - Expression of stress proteins in cultured HT29 human cell-line; a model for studying environmental aggression. AB - The current study was undertaken to investigate the expression of stress proteins (HSP) in cultured human HT29 cells submitted to stressing events under in vitro conditions. Heat shocks (45 degrees C, for 15-60 min) or cold shocks (+ 1 degree C for 4 hr) were found to modify cell growth (growth curves) and to enhance HSP expression. In most cases, changes in HSP expression are much more pronounced than changes in cell growth. Exposure to 8% ethanol for 15 min resulted in both growth inhibition and HSP overexpression. Propanol-1 was found to be more toxic since 5% concentration given for 15 min stops cell growth. 2.5% propanol-1 for 15 min induces a slight reduction of cell growth but a clear-cut overexpression of stress proteins. We conclude that expression of stress proteins, especially those of the HSP68/70 family, constitutes a more sensitive response than changes in growth rate in case of external aggression. This could make our model an interesting biological sensor to environmental physical or chemical pollutants. PMID- 7788561 TI - The purification and properties of glutathione reductase from the cestode Moniezia expansa. AB - Glutathione reductase has a central role in glutathione metabolism and as such is a potential target for chemotherapy. The aim of the work was to purify and characterise glutathione reductase from the cestode Moniezia expansa and to compare the properties of the helminth enzyme with its mammalian counterpart. The enzyme was purified by a combination of anion exchange and affinity chromatography and further characterized by chromatofocusing and gel electrophoresis. Analysis revealed a single isoenzyme of glutathione reductase in Moniezia expansa, with a pI of 5.8. The enzyme was a homodimer of native molecular weight 114 kDa, subunit weight 63 kDa. Enzyme activity was affected by buffer concentration and the presence of monovalent sodium salts. The pH optimum was 7.4 with NADPH as cofactor and 5 with NADH. The Kma for oxidized glutathione was 76 microM and for NADPH and NADH, 21 and 350 microM respectively. In addition to oxidized glutathione only the mixed disulphide between CoA and glutathione (CoASSG) showed any significant activity as substrate. The cestode enzyme was inhibited by a variety of compounds including arsonic derivatives, 2,4,6 trinitrobenzene sulfonate 1,3-bis (2-chlorethyl)-1-nitrosourea and oxidized glutathione. In conclusion the glutathione reductase of M. expansa resembles the mammalian enzyme in its general physical properties and its substrate and inhibitor profile. However, the parasite enzyme shows an unusually high activity with the mixed disulphide of coenzyme A and glutathione (CoASSG) and appears to be more sensitive to inhibition by sodium ions. PMID- 7788562 TI - Effect of dietary fiber at weaning on protein glycosylation in the rat small intestine. AB - Changes in protein glycosylation which can be modulated by dietary factors are observed in the rat intestinal mucosa at the weaning period. Experiments were performed to evaluate the involvement of dietary fibers in the regulation of such modifications. Groups of rats were abruptly weaned at 19 days of age on semi synthetic diets differing in dietary fiber content (fiber-free, 10% pectin or 10% cellulose) given for 4 and 10 days. Glycoprotein sugars, activities of the fucosylation pathway and caecal contents were analyzed. Neutral sugar contents in glycoproteins of the small intestinal mucosa were increased in teh fiber-fed groups as compared to fiber-free group, only after 4 days but not after 10 days of diet. Diet-induced modifications in the glycoprotein fucose content of the small intestinal mucosa are partly explained by the coordinated evolution of different activities involved in the fucosylation pathway (GDP-fucose production and breakdown, fucosyltransferase and fucosyltransferase inhibitor). Caecal contents of short chain fatty acids were significantly different between the three groups after 4 but not after 10 days of diet. There was no correlation between caecal short chain fatty acid contents and activities involved in the fucosylation pathway. The introduction of dietary fibers at weaning induced marked but transient changes in glycoprotein sugars and the fucosylation pathway. The results demonstrate that fucosylation is regulated in several ways including changes in fucosyltransferase activity but that caecal fermentation of dietary fibers was not directly responsible for the observed changes. PMID- 7788563 TI - Purification and identification of two distinct isoforms of rabbit pancreatic cholesterol esterase. AB - Cholesterol esterase (CEases; E.C. 3.1.13) has been purified to homogeneity from rabbit pancreas. The method of purification consists of homogenization of total pancreas, high speed centrifugation, anion exchange column chromatography on S Sepharose, size exclusion on Sephacryl followed by affinity chromatography on heparin agarose. During the purification procedure, two distinct isoforms of CEases have been identified. Both forms are similar in their molecular weights, bile salt requirement and pH optima but differ in their sensitivity to heparin. Isoform-I is resistant and isoform-II is sensitive to heparin. In the normal pancreas of the adult rabbit, the amount of each of the enzymes appears to be in equimolar concentrations. Physiological significance of the existence of heparin sensitive and resistant forms by the same tissue is unclear. In view of the significant role played by heparin in the modulation of CEase activity and several other physiological functions, these two isoforms may have different mechanisms of action on the hydrolysis of carboxyl esters of cholesterol and vitamins. PMID- 7788564 TI - Latex allergy. PMID- 7788565 TI - Plant allergens on pauci-micronic airborne particles. PMID- 7788566 TI - IgE, smoking and lung function. PMID- 7788567 TI - Atopic dermatitis--the skin manifestation of atopy. PMID- 7788568 TI - Topical levocabastine--an effective alternative to oral antihistamines in seasonal allergic rhinoconjunctivitis. PMID- 7788570 TI - Seasonal appearance of grass pollen allergen in natural, pauci-micronic aerosol of various size fractions. Relationship with airborne grass pollen concentration. AB - In a study during the 1993 grass pollen season at Leiden, the relationship between atmospheric pollen allergen carried by five size fractions of pauci micronic (few microns) particles and the grass pollen count was investigated. Sampling was carried out on dry days, and atmospheric pollen allergen in the particle fractions was assessed by a RAST-inhibition assay while grass pollen quantities were measured with a volumetric pollen trap. It appears that the atmospheric presence of grass pollen allergen in all size fractions is restricted mainly to the period of presence of grass pollen grains. Before and after the grass pollen season atmospheric grass pollen allergen quantities are generally very low. It is concluded that a routinely performed grass pollen count is a reliable measurement for the estimation of the amount of atmospheric grass pollen allergen, also in the pauci-micronic particle fraction. PMID- 7788569 TI - The allergen of Ficus benjamina in house dust. AB - Ficus benjamina, a member of the Moraceae family, is a tropical, non-flowering green plant which is widely used for ornamental purposes. It is an occupational allergen in plant keepers but sensitization is also increasingly found in non occupationally exposed atopic and non-atopic patients. The allergen of Ficus benjamina is located in the plant sap, a so-called latex. By radioallergosorbent test-(RAST)-inhibition studies allergen could also be demonstrated in the dust collected from the leaf surface and in dust samples from the floor of rooms where the plant was placed. These findings could result in more extensive preventive measures in patients sensitized to Ficus benjamina. In addition there is some evidence that possibly a crossreactivity between latex of Ficus benjamina and latex from the rubber tree Hevea brasiliensis, a member of the Euphorbiaceae family, may exist. PMID- 7788571 TI - House dust mite allergen levels in two cities in Canada: effects of season, humidity, city and home characteristics. AB - The homes of 120 patients with asthma, 57 in Vancouver and 63 in Winnipeg, were studied. The characteristics of the homes were assessed by a questionnaire. Dust samples were collected and the indoor relative humidity was measured four times during the year covering all four seasons in both cities. Mite allergen levels were determined using monoclonal antibodies against Der p I and Der f I by the ELISA method. The mean levels of both mite allergens in mattress and floor samples in the homes in Vancouver and in Winnipeg were relatively low for all seasons. Mite allergen levels were found to be associated with city, season and individual home differences. They were significantly higher in Vancouver than in Winnipeg. Der p I and Der f I in mattress samples in both cities and Der f I in floor samples in Vancouver, varied by season. The indoor relative humidity level in the homes in Vancouver were also significantly higher than those in Winnipeg. There was, however, no significant association between the levels of indoor relative humidity and the levels of mite allergens after adjusting for variations in city, season and individual home. Although individual home differences were highly associated with mite allergen levels, only a few home characteristics were found to be related to mite allergen levels such as the type and the age of the home, the type of heating, the use of feather pillows and the number of occupants in the homes. Whether low levels of mite allergens are partially responsible for the relatively low prevalence of childhood asthma in Canada remains to be investigated. PMID- 7788572 TI - Differences between specificities of IgE and IgG4 antibodies: studies using recombinant chain 1 and chain 2 of the major cat allergen Felis domesticus (Fel d) I. AB - IgE- and IgG4 antibodies were compared for reactivity with recombinant chain 1 and chain 2 of the cat allergen Felis domesticus (Fel d) I. Recombinant chain 1 and chain 2 were coupled to sepharose and tested in IgE- and IgG4 radioallergosorbent test (RAST) experiments. Substantial IgE- and IgG4 binding was found. The fraction of Fel d I-specific antibody that bound to the recombinant chains was calculated. For chain 1, the mean value of this fraction was 0.30 for IgE and 0.23 for IgG4 (P = 0.05). For chain 2, the mean value of this fraction was 0.19 for IgE and 0.13 for IgG4 (P = 0.02). These results indicate that differences in fine specificity exist between IgE and IgG4 antibodies. Moreover, these findings support our results with chemically prepared peptides derived from these two chains and suggest that the B cells producing IgE antibodies are more likely to recognize a less 'native' form of Fel d I, compared with IgG4. PMID- 7788574 TI - Immunological study of Melkersson-Rosenthal syndrome. Lack of response to food additive challenge. AB - A study was made of six patients with Melkersson-Rosenthal syndrome (MRS) to establish the aetiological role of foodstuffs and/or additives and the possible associated immunological alterations. In all cases Melkersson-Rosenthal syndrome (MRS) was diagnosed both clinically and histologically, excluding other causes of orofacial granulomatosis (OFG). A detailed study of possible triggering factors was performed in all patients. Blood analysis, x-rays and cultures, were always within normal limits, with the exception of the finding of circulating immune complexes (CICs) in three patients with facial palsy associated, and C-reactive protein positivity in two patients who presented persistent labial oedema. All patients were subjected to skin-prick tests with common inhalant allergens and with foods when sensitization to foods were suspected, and patch tests with European Standard Series and pastry components, organic dyes, perfumes and fragrances series. The results were negative in all cases. When asymptomatic, the patients were subjected to a double-blind oral challenge, under placebo control, with additives (monosodium glutamate, tartrazine, sulfites, erythrosine, paraoxybenzoate, sodium benzoate, lactose, aspirin, and annate), which was again negative. In no case did the patients refer the appearance of outbreaks with exposure to foods or contactants, and the course of the disease was unaffected by exclusion diets and the elimination of contactants. To conclude, we observed no sensitization to foods, additives or contactants in our patients. Likewise, there were no antecedents of atopy or hereditary predisposition related to the aetiopathogeny of MRS. The significance of the CIC encountered only in patients with facial paralysis remains to be established, due to the limited number of patients studied. PMID- 7788573 TI - HLA-DR expression is induced on keratinocytes in delayed hypersensitivity but not in allergen induced late-phase reactions. AB - In view of increasing evidence suggesting an active immunoregulatory role of the skin keratinocytes and the observation that the differentiation of allergen specific T lymphocytes is critical in the development of allergy, we evaluated epidermal expression of HLA-DR antigen in skin reactions induced with an atopen (house dust mite) and with an non-atopic antigen (Hemocyanin). Two groups of patients with house dust mite (Dermatophagoides pteronyssinus [Der p]) allergy were compared, one group was skin tested with Der p, the other group was immunized and subsequently skin tested with Helix pomatia Hemocyanin (HPH). Biopsy specimens taken at 48 h after the HPH (n = 11) and Der p (n = 11) tests were analysed immunohistologically. Reactions in both groups were comparable in size. Immunohistological analysis showed domination by CD4+ lymphocytes. Expression of HLA-DR antigen by epidermal keratinocytes was observed in six out of 11 of the HPH induced reactions, but in none of the Der p induced reactions. Eosinophils were spotted only throughout the Der p induced reactions, showing a good correlation with the number of CD4 positive lymphocytes. The lack of HLA-DR expression by keratinocytes during the allergen-induced reaction, compared with the Hemocyanin induced reaction can be the result of a difference in cytokine profile of the lymphocytes dominating the dermal infiltrate. On the other hand evidence exists that defective HLA-DR expression by keratinocytes enhances antigen induced lymphocyte activation, and may thus contribute to the development of allergen-specific T-lymphocytes. PMID- 7788576 TI - [Isolating fetal cells from maternal blood for noninvasive prenatal diagnosis- from patent to clinical application]. PMID- 7788575 TI - Comparative study between European and American species of Polistes using sera from European sensitized subjects. AB - Although the different vespid species of the genus Polistes are found all over the world, studies about allergy sensitization to these species have been made mainly in North America. We studied the specific IgE in a large group of sera from patients sensitized to Polistes dominulus (PD) and determined the crossreactivity with another important European Polistes (P. gallicus [PG]) and with five American relevant species of this genus: P. exclamans (PE), P. fuscatus (PF), P. metricus (PM), P. annularis (PAN) and P. apachus (PAP). Studies indicated that 96.7% of sera with IgE positive to PD were positive to PG. No case positive to just PG was found. The comparison of these two European species with the American relatives indicated that most cases were positive to all the insects although there were significant differences in the radioallergosorbent test (RAST) value. These results were confirmed by RAST inhibition studies, and indicate that although the European and American species are closely related, species specific allergenic differences exist. These data suggest that in vivo studies should be carried out in order to determine the sensitivity and specificity of the European venoms compared with the American species. PMID- 7788577 TI - [Discriminant analytic model for prognostic assessment of pregnancies at risk for premature labor]. AB - We examined 114 women with preterm labor using discriminance analysis to assess predictive values in terms of prolongation of gestational age and gestational age at the time of delivery. We used parameters like medical history, clinical features, infections, Doppler sonography and cardiotocography. Maternal temperature, cardiotocographic findings, premature rupture of membranes, number of abortions and pregnancy terminations and cervical dilatation at the time of admission contribute significantly to predict prolongation of pregnancy (< or = as well as > 7 days). Our results from this analysis showed sensitivity and specificity of 0.70 and 0.97 and positive and negative predictive values of 0.89 and 0.91, respectively. We observed significant differences concerning parameters like preterm rupture of membranes, cervical dilatation, pathological bacteria in the vagina and pathological Doppler values between subsequent preterm and term deliveries in pregnancies with a prolongation of > 7 days was. Upon reclassifying our results, we obtained sensitivity and specificity of 0.69 and 0.89 and positive and negative predictive values of 0.78 and 0.84, respectively. Early prognostic assessment of preterm labor can be made with discriminance analysis. The results inspire us to perform a prospective examination of the therapy plan that we have obtained. PMID- 7788579 TI - [Premature labor in HIV infected women. Swiss "HIV and Pregnancy" Study Group]. AB - In the Swiss Study "HIV and pregnancy" we observed 153 singleton pregnancies of HIV-positive women. 23 (15%) of those ended with a premature delivery. For drug addicts (n = 100), the incidence of prematurity, 20%, significantly higher than in those free of drugs (n = 53) with 5.6%. The most frequent cause of prematurity was premature labor or rupture of the membranes (n = 13), followed by maternal illness (n = 8) and fetal complications (n = 2). Women with premature delivery tended to have lower CD4 cell counts than those with term delivery (29.4% vs 12.0% with < 200 CD4 cells/microliters). Low CD4 cell counts and drug consumption are two independent but cumulative risks for severe infections. 16 of the 153 women (12 with, 4 without drug consumption) had severe infections during pregnancy; in 4 cases (25%), this led to prematurity. The most common infection was pneumonia (14/16), further one case of pyelonephritis and one of cerebral toxoplasmosis. Two of these 16 infants (12.5%) were HIV-positive. We could not confirm a relationship between prematurity and vertical HIV transmission. Of the HIV-classified children, 3/18 (16.7%) premature infants and 16/74 (21.6%) term infants were infected. PMID- 7788578 TI - [Morbidity and mortality of retarded and normal weight premature infants]. AB - Differences of fetal outcome between appropriate for gestational age (AGA) and small for gestational age (SGA) preterm newborns with birth weight below 2500 g and gestational age ranging from 27 to 36 weeks have been evaluated. As described by Rohrer SGA have been divided into symmetrical retarded and asymmetrical retarded newborns using ponderal index. Therefore distribution of ponderal index on our local population has been analysed. SGA more often had an Apgar score below 6 five minutes post partum (p = 0.01) and their mothers more often announced abuse of nicotine during pregnancy. AGA have been on respiratory ventilation significantly longer than SGA (p = 0.001) and photo therapy because of hyperbilirubinaemia more often had to be performed on AGA (p = 0.02). AGA have spent a longer time at the neonatal intensive care unit than SGA (p = 0.0006). No differences could be found in mortality between AGA and SGA. Preterms with low ponderal index had no different outcome than SGA with normal ponderal index. PMID- 7788580 TI - [Rate of prematurity and perinatal mortality in the Yaounde (Cameroon) University Gynecologic Clinic 1982-1992> An analysis of 680 cases]. AB - The authors made an analysis of perinatal mortality on 680 cases of premature births recorded between 1982 and 1992 in the CHU maternity, Yaounde (Cameroon). During this period, 13,555 births were recorded. The frequency of premature births stood at 5%. The most important etiological factors responsible for these 680 premature cases were depicted as malaria infection and anemia (22.2%), premature rupture of the membranes (13%), multiple pregnancies (11.9%), preeclampsia (10.2%), antepartnal bleeding (5.7%), and urogenital infections (5.0%). The perinatal mortality rate was 16.7% (114 cases). There were 37 cases of antepartual foetal deaths (5.4%), 24 cases of intrapartual foetal deaths (3.2%) and 31 cases of neonatal deaths (4.5%). Perinatal mortality reduced with an increase in the gestation period and the weight of the foetus. The authors noted with astonishment that perinatal mortality was twice as high in cases of non ruptured membranes (19.5%) when compared to premature ruptures of the membrane (10.2%). A plus 30 minutes duration of the expulsion phase was estimated to be a factor that increases perinatal mortality. Breech presentation with a 32.8% perinatal mortality, when compared to cephalic presentation (7.5%), portrays an important risk factor in premature births. Perinatal mortality of premature babies in cases of spontaneous births is two time higher (16.2%) than in cases of caesarean section (7.8%). PMID- 7788581 TI - [Results of neonatal hearing screening with transitory evoked otoacoustic emissions]. AB - From 1. 10. 1992-31. 12. 1993 a hearing screening was performed in 994 preterm and term babies (765 healthy neonates and 229 neonates with risk factors for hearing loss) by means of transient evoked otoacoustic emissions (TEOAE). There was a bilateral absent of emissions in 4.3% of the healthy neonates and 11.8% of the risk babies. 8 from 32 healthy neonates and 10 from 22 risk babies also had a negative test result in the control investigation. 16 of these children showed in 7 cases a severe hearing impairment in expanded pedaudiological investigations. The registration of TEOAE is a recommendable method for a hearing screening in neonates. PMID- 7788582 TI - [Comparison of surface tension with determination of the L/S ratio in amniotic fluid for prediction of fetal lung maturity]. AB - In 83 specimen of amniotic fluid both a dynamic measurement of the surface tension by the Wilhelmy-balance and a determination of the lecithin-sphingomyelin ratio were performed in 1987-1992 in order to predict a respiratory-distress syndrome (RDS) of the newborn. 7 cases showed divergent results of both methods. In comparison with the measurement of surface tension by the Wilhelmy-balance, determination of the lecithin/sphingomyelin-ratio showed more false positive results (4:1). Both methods provided false negative results in two cases each. In two cases both methods showed false positive results, with RDS occurring in spite of predicted lung maturity. In our high risk-collective 5 of 83 newborns developed a severe RDS. All of them were delivered by caesarean section. A secondary deficiency of surfactant as a result of fetal hypoxia or acidosis as well as a possible influence of the way of delivery might be responsible for the development of RDS. The Wilhelmy-balance, which can be used as a bed-side-method, provides similar results in the prediction of fetal lung maturity compared to the L/S-ratio. PMID- 7788584 TI - Canadian Ophthalmological Society annual meeting and exhibition. Victoria, British Columbia, June 24-27, 1995. Abstracts. PMID- 7788585 TI - History of nursing in British Columbia captured on tape. PMID- 7788583 TI - [Development of a plastic capillary tube for Saling fetal blood analysis. Evaluation of pH-metry with standard references]. AB - In order to avoid mouth suction and danger of glass breakage during collection and to avoid mixing of the sample with a piece of wire and an external magnet immediately after collection, an unbreakable plastic capillary tube was designed with increased heparin coating and surface and reduced diffusion distance. For assessing agreement between pH measurements of blood samples obtained with the new plastic capillary tube and a commercial glass capillary tube, umbilical blood pH-values of 41 births were analyzed simultaneously by both methods. The mean difference between paired pH-values, the corresponding 95%-confidence interval and the true limits of agreement were calculated. The pH-values obtained with the plastic capillary tube are systematically lower, with a mean pH decrease of 0.009 units, and there is an additional random variation with a standard deviation of 0.009 pH units. The true limits of agreement: [-0.031, 0.013] represent the interval of the worst expected pH difference. The increased heparin availability in the plastic capillary tube may be the reason for the systematic pH deviation of -0.009 units. However this difference does not seem to be clinically relevant and the statistical evaluation shows a sufficiently good agreement between the pH measurements. PMID- 7788586 TI - The voice of nursing has to be loud and clear. PMID- 7788587 TI - Between women: nurses and family caregivers. PMID- 7788589 TI - Some reflections on the nurse practitioner movement: potential danger, exciting possibilities. PMID- 7788590 TI - Nurses' work: balancing personal and professional caregiving careers. AB - Forty full-time nurses who were also responsible for providing care to individuals in their private lives volunteered for a qualitative study of combined caregiving careers. Each respondent kept a diary of caregiving activities during two representative 24-hour periods, and was interviewed prior to, and after diary-recording. Most nurses experienced high levels of stress associated with caregiving in both their professional and private lives. In general, they were relatively satisfied with their lives in both spheres, and felt a slightly greater sense of control in their work lives than in their home lives. Regarding the tensions/conflicts they alluded to, the following themes emerged: an ethic of high expectation, feeling torn between two worlds, a sense of working in isolation, and working in overdrive. The rewards/benefits included remuneration, recognition and self-esteem, opportunities for personal growth, and opportunities for family growth. PMID- 7788588 TI - Women's paid/unpaid work and health: exploring the social context of everyday life. AB - Literature from various disciplines was reviewed to obtain a description of the working lives of Canadian women. This analysis drew on the work of Smith (1987, 1990) and other feminist and critical theorist authors who have argued that much of women's work remains invisible and undervalued. Patterns of normative thought or social ideology may obscure the extent and value of women's contributions. It is suggested here that an "ideology of separate spheres" operates in the designation of paid activity in the public sphere as work, whereas activities pursued in the private sphere of the home are overlooked. It is further argued that women's heavy involvement in unpaid activities that support and sustain others results in a state of lesser citizenship, and women's own prerequisites of health are often compromised. Women's work often takes place outside the formal economy, within a "shadow" or subsistence economy (Illich, 1981) which is essential for the continued health of others. PMID- 7788591 TI - Mothers of children with chronic conditions: supportive and stressful interactions with partners and professionals regarding caregiving burdens. AB - Ninety mothers appraised the specific sources and types of social support they received in relation to specific types of demands of caring for a child with a chronic condition. Qualitative data were collected during home interviews with the mothers of children with diabetes, spina bifida, or cystic fibrosis. Virtually all of the mothers described primary caregiver demands that were directly related to the child's condition, such as physical care, health care in illness situations, and the child's psychological and social development. Many mothers also reported secondary demands related to their own needs, family roles and relationships, and the mother's activities outside the home. Mothers experienced gaps in the support provided for specific caregiving burdens and encountered stressful interactions with their partners and health professionals in particular. PMID- 7788592 TI - Women's health. PMID- 7788593 TI - Leadership: a nursing perspective. AB - The Task Force for Collaborative Nursing Education Models was a successful collaboration involving female nurse administrators. The nature of leadership in the Task Force was studied as part of a larger research project examining the process of collaboration that evolved over the 40 months of its existence (October 1987-February 1991). A retrospective qualitative case study approach was used. Data were collected from an analysis of documents that had been generated by the group, and from 36 semi-structured interviews with the 28 Task Force members. Findings and conclusions about leadership were validated during a final group interview with eight selected members. Findings of this study support the following contentions: women lead differently than men, and leadership is a collective process rather than a specialized role assumed by a single person who influences the work of other group members. Leadership was also found to rotate among group members according to the issue being considered and the expertise of those present. These findings did not support the positivist theories of leadership prevalent in current nursing management text books. PMID- 7788594 TI - 30th Meeting of the Canadian Congress of Neurological Sciences. Victoria, British Columbia, June 20-24, 1995. Abstracts. PMID- 7788596 TI - Necessity is the mother of invention. PMID- 7788595 TI - The dysvascular lower limb in blunt trauma: a multidisciplinary challenge. PMID- 7788597 TI - Peutz-Jeghers syndrome. PMID- 7788598 TI - Radiology for the surgeon. Case 3. Presentation. Meckel's diverticulum. PMID- 7788599 TI - The traumatized ischemic lower limb: a search for the optimal treatment. AB - OBJECTIVE: To improve the surgical results of closed injuries of the femoropopliteal arterial axis. DESIGN: A retrospective study over 20 years. SETTING: A university-affiliated hospital. PATIENTS: Fifty-nine patients (95% male, mean age 29 years) with 63 blunt injuries to the femoropopliteal arterial axis, treated by eight surgeons. INTERVENTIONS: Thrombectomy with saphenous vein patch arterioplasty; primary end-to-end anastomosis, saphenous vein interposition and saphenous vein bypass. MAIN OUTCOME MEASURES: Death rate, incidence and causes of amputation and late outcome of salvaged limbs. RESULTS: The death rate was 8.5%, the amputation rate was 25% and the long-term disability of salvaged limbs was 80%. Earlier ablation of two infected extremities and of another one responsible for acute renal failure would have reduced the death rate to 3% at the expense of increasing the amputation rate to 35%. The level of arterial disruption, the degree of soft-tissue damage and the ischemia time greatly influenced limb survival and long-term disability. The ischemia time is the single factor that can be modified by the medical team. If its duration is less than 15 hours, the amputation rate decreases. However, the ischemia time should be reduced to less than 7 hours to assure limb salvage without sequela. CONCLUSIONS: Early diagnosis and priority of the arterial repair over associated orthopedic injuries are essential to reduce the ischemia time. Despite successful revascularization, early amputation is the only means of saving life in some cases. PMID- 7788600 TI - Management of the compromised lower extremity. AB - Musculoskeletal injury associated with vascular compromise is a limb-threatening situation. When these injuries are associated with open fractures, the risk of limb loss is increased. In the case of an open fracture of the tibia associated with vascular compromise distal to the popliteal artery trifurcation, limb salvage is rarely indicated. Attempts at limb salvage in open tibial fractures are associated with a high risk of complication, prolonged recovery and poor function. Early amputation is more effective than delayed amputation. PMID- 7788601 TI - Reconstructive surgery for lower limb salvage. AB - The authors review the principles of reconstructive surgery for lower limb salvage after severe lower limb trauma to determine factors that have been used as decision-making criteria for limb salvage or amputation in severe lower extremity injuries and the methods of reconstruction and their outcome. The use of scoring systems and their value in acute decision making (primary amputation or limb salvage) are described. Soft-tissue reconstructive techniques, with emphasis on the use of flaps and the importance of selecting the best technique and time for the reconstruction are reviewed. Skeletal reconstructive techniques are described, including available options and currently held views on indications and use of the best contemporary methods. It is essential for the physician to make a good initial decision on the need for primary amputation or limb salvage. A multidisciplinary approach is fundamental to successful salvage. PMID- 7788602 TI - The history of vascular surgery in Canada. AB - The clinical specialty of vascular surgery in Canada began before the Second World War with the introduction of heparin into clinical practice by Gordon Murray of Toronto. He showed that heparin could prevent thrombosis during the repair of blood vessels and was useful in the treatment of spontaneous arterial and venous occlusion. The unfavourable war experience with arterial ligation for trauma led to an interest in the direct repair of vascular injuries by surgeons returning to civilian practice. Embolectomy, first performed in the late 1940s, was the other early vascular operation. Aortic surgery initially depended upon the use of cadaver homografts, and a number of programs were started in the early 1950s, only to be abandoned as synthetic grafts became available. Infrainguinal bypass grafting with saphenous vein evolved in clinics set up to treat varicose veins and varicose ulcers. The first in-situ grafts were done by Paul Cartier of Montreal in 1960. By this time, reconstruction for aneurysmal and occlusive disease was well established throughout Canada. Specific fellowships in vascular surgery were first offered in the 1970s, as clinical units were set up in teaching hospitals. Surgeons concentrating on vascular disease founded the Canadian Society for Vascular Surgery (CSVS) in 1978 and approached the Royal College of Physicians and Surgeons of Canada to establish training requirements in their specialty. The first qualifying examination was held in 1983, and by 1994 certificates of special competence had been awarded to 178 candidates. The pioneers in Canadian vascular surgery are acknowledged and their contributions summarized. PMID- 7788603 TI - Ancrod as prophylaxis or treatment for thromboembolism in patients with multiple trauma. AB - OBJECTIVE: To report the initial clinical experience with fibrinogen depletion using ancrod as prophylaxis and treatment for deep vein thrombosis and pulmonary embolism (DVT/PE) in patients with multiple trauma. DESIGN: A series of cases, selected because of their extreme risk of DVT/PE or because of the appearance of thromboembolic complications despite prophylaxis using conventional methods. SETTING: University teaching hospital. PATIENTS: A referred sample comprising 30 patients with multiple blunt trauma. The mean injury severity score was 30. Most cases involved a combination of lower extremity, pelvic and chest injuries. INTERVENTIONS: Fibrinogen was slowly depleted over 24 to 36 hours and the concentration maintained at 0.2 to 0.5 g/L thereafter. Ancrod was continued prophylactically (22 patients) or for established DVT/PE (8 patients) until the patients were mobilized or until there was no longer a contraindication to heparin, or until treatment with warfarin became practical. MAIN OUTCOME MEASURE: Monitoring for DVT by duplex ultrasonography or iodine-125-labelled-fibrinogen scanning, whichever could be applied. RESULTS: Twenty patients were treated with ancrod for prophylaxis from the outset because it offered theoretic and practical benefits over other methods. No patient treated with ancrod for prophylaxis suffered a clinically significant DVT/PE. Patients in whom heparin prophylaxis failed and who experienced thromboembolic complications were effectively managed with ancrod. There were no deaths and no bleeding complications specifically due to the therapy. CONCLUSIONS: Slow depletion of fibrinogen with ancrod may provide a safe and effective means to prevent DVT/PE in multiple trauma patients or to treat DVT/PE when the risk of bleeding from heparin is great. This initial experience should be evaluated by a randomized controlled trial. PMID- 7788604 TI - Reoperation for cysts of the thyroglossal duct. AB - OBJECTIVE: To determine the causes of recurrence of thyroglossal duct cysts (TDCs). DESIGN: A case series. SETTING: A university-affiliated children's hospital. PATIENTS: Between 1974 and 1990, 121 children were treated for TDCs. They ranged in age from 1 month to 18 years. Of these 121 children, 23 had recurrent TDC. INTERVENTIONS: Simple aspiration of the cyst, incision and drainage, cystectomy without hyoidectomy and the Sistrunk operation. MAIN OUTCOME MEASURES: Initial procedures that led to recurrence and procedures that resulted in cure. RESULTS: Six children had recurrence of TDCs after simple cystectomy without hyoidectomy; all were cured by the Sistrunk operation. Fourteen children with infected cysts initially underwent a variety of procedures with recurrence and were eventually managed by the Sistrunk operation. TDCs recurred in eight of these. Three children without infected cysts had recurrence after the Sistrunk operation. Of 34 TDCs infected initially, 40% recurred, whereas of 87 TDCs that were not infected initially, only 8% recurred. CONCLUSION: Simple cystectomy without hyoidectomy and pre-existing infection are the main causes of recurrence of TDCs. PMID- 7788605 TI - Routine outpatient laparoscopic cholecystectomy. AB - OBJECTIVE: To determine what proportion of patients booked for elective cholecystectomy can be treated on an outpatient basis and what criteria will predict the need for hospital admission. DESIGN: A prospective analysis. SETTING: A 306-bed, nonteaching, acute-care community hospital on the outskirts of a major urban centre. PATIENTS: One hundred consecutive patients in private referral practice scheduled for outpatient laparoscopic surgery between November 1992 and January 1994. INTERVENTION: Laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: The proportion of patients who successfully avoided hospital admission, the degree of discomfort, complications and the objective criteria that assist in predicting the need for initial or eventual hospital admission. RESULTS: Outpatient cholecystectomy was successful in 87% of the patients, and patient acceptance of the procedure was good. Advanced age, major associated health problems, acute cholecystitis and longer operations were the criteria most likely to lead to hospital admission, although none of these factors, alone or in combination, was a contraindication to outpatient cholecystectomy. CONCLUSIONS: Outpatient laparoscopic cholecystectomy can be performed successfully in most patients. There are four criteria that increase the likelihood of hospital admission after this procedure. PMID- 7788606 TI - Modern war surgery: the experience of Bosnia. 1: Deployment. AB - In the first of two papers on the experience of a Canadian military surgical team in the former Yugoslavia, the authors describe the deployment of the field surgical hospital, the medical structure that supported the Canadian battle group. The hospital was made up of tent sections erected within an unfinished concrete factory building. The hospital comprised a treatment area for sick parades and reception, a pharmacy, a resuscitation area for nonambulatory casualties, a laboratory, an x-ray section, an operating room and sterilization section and a ward. The hospital could be mobilized if necessary. The setup proved to be functional for the treatment of injured soldiers. Although long delays were expected because of difficulties in transporting the injured, the patients reached the hospital in a reasonable time after injury and could be treated satisfactorily. During the period of its deployment, this hospital was used more than any other Canadian hospital in the United Nations mission. This experience allowed the authors to identify deficiencies and to correct them quickly. PMID- 7788607 TI - Pulsatile buttock mass: report of two cases and a review of the literature. AB - The presence of any pulsatile mass suggests an underlying aneurysm. When such masses occur in the buttock, the differential diagnosis includes aneurysms arising from branches of gluteal vessels or aneurysms developing in a persistent sciatic artery (PSA). The investigation and management of two patients with pulsatile masses are described. Review of the embryologic aspects of these masses and the important literature on the subject led to the conclusions that when a pulsatile buttock mass is encountered, an anomalous PSA should be suspected. A gluteal artery aneurysm can be treated by ligation or occlusion, but for a sciatic artery aneurysm surgical ablation is necessary and distal perfusion must be achieved postoperatively. PMID- 7788608 TI - Perforation of the small bowel: a case report. AB - Nontraumatic perforation of the small bowel is rare. A 71-year-old man presented with a perforated jejunum 8 weeks after receiving streptokinase therapy for acute myocardial infarction. This was complicated by a bleeding duodenal ulcer, renal failure, ischemia of one toe and confusion. Renal biopsy showed cholesterol emboli. Examination of the resected specimen of jejunum revealed multiple cholesterol emboli but no other disorder. Cholesterol embolization has been associated with angiography, vascular surgery and thrombolytic therapy for myocardial infarction. Acute renal failure and ischemia of the digits as seen in this patient is also a common presentation of cholesterol embolization syndrome. PMID- 7788609 TI - Long-term central venous access through the inferior epigastric vein. PMID- 7788610 TI - Radiology in surgical journals. PMID- 7788611 TI - Pelvic lymphadenectomy: laparoscopy or laparotomy? PMID- 7788612 TI - [Atypical depression: evolution toward a specific pharmacologic and efficacious treatment?]. AB - The present article reviews different concepts of atypical depression. Of these, major depression associated with panic disorder would have a specific meaning according to some pharmacological and prognosis studies. It seems that this type of depression is quite frequent and has a significantly worse prognosis than major depression alone. Controlled studies comparing the efficacy of tricyclic antidepressants to phenelzine concluded in favour of the latter in general. It is generally thought that atypical depression would respond better to monoamine oxidase inhibitors (MAOI), but it would seem that it is mainly major depression associated with panic disorder that could predict this kind of response to treatment. Second generation antidepressants have not been studied systematically for this purpose even though preliminary reports seem promising. PMID- 7788613 TI - Symptoms of post-traumatic stress disorder in 11 police officers. PMID- 7788614 TI - RE: The need for research and ethical safeguards in special populations. PMID- 7788615 TI - Desipramine plasma levels and treatment response in panic disorder. PMID- 7788616 TI - Organic depression associated with flunarizine. PMID- 7788618 TI - The mental health of immigrant and refugee children. PMID- 7788617 TI - Insula and obsessive-compulsive disorder. PMID- 7788619 TI - Learning how to differ: agreement and reliability statistics in psychiatry. AB - Whenever two or more raters evaluate a patient or student, it may be necessary to determine the degree to which they assign the same label or rating to the subject. The major problem in deciding which statistic to use is the plethora of different techniques which are available. This paper reviews some of the more commonly used techniques, such as Raw Agreement, Cohen's kappa and weighted kappa, and shows that, in most circumstances, they can all be replaced by the intraclass correlation coefficient (ICC). This paper also shows how the ICC can be used in situations where the other statistics cannot be used and how to select the best subset of raters. PMID- 7788620 TI - Immigrant and refugee children in Canada. AB - In view of Canada's commitment to immigration, understanding the sources of successful adaptation by immigrant and refugee children is vital. This paper reviews the literature on the mental health of migrant children and suggests an agenda for future research. PMID- 7788621 TI - Alcohol and polysubstance abuse among women. AB - A review of the literature in this relatively new field highlights the legitimacy of gender-specific research on substance abuse in women. Consistent findings compared to men include a higher physical vulnerability to alcohol, a higher risk of assortative mating, the reported association of traumatic events with the onset of substance abuse, a higher psychiatric comorbidity and a shorter interval between first problem and first treatment episode. Intravenous drug use remains the major source of growth of HIV infection among women. Family assessment and treatment as well as the involvement of female role models are critical to the recovery process. Gender-specific services may be recruiting women who might not otherwise have sought treatment for their substance abuse. Further investigation is required in order to distinguish the relative significance of the genetic versus environmental vulnerability of women, the impact of rapidly changing social mores on the onset, pattern and course of substance abuse, possible gender specific alcohol typologies, the validity of the recall of traumatic events as well as the program variables required in reaching out and engaging women on the path to recovery. PMID- 7788622 TI - Screening for post-partum depression in a community sample. AB - OBJECTIVE: This study undertook to estimate the prevalence of post-partum depression in the community by means of telephone screening. Demographic correlates of post-partum depression were also investigated. METHOD: The sample was identified through two community health centres. Over a period of 17 months, 1559 childbearing women were screened at six weeks post-partum, using the ten item Edinburgh Postnatal Depression Scale (EPDS). RESULTS: The prevalence of post partum depression was estimated to be 6.2%, using a cut point of 10 on the EPDS, and 3.4% using the more stringent cut point of 12. Women who were not working or those with lower occupational status, were at greater risk for depression. Recent immigrants, particularly those who were not working or who had given birth to a second child, were also at higher risk. CONCLUSION: Telephone screening for post partum depression is feasible, and can aid in the identification of women at risk. PMID- 7788623 TI - Behavioural inhibition, attachment and anxiety in children of mothers with anxiety disorders. AB - OBJECTIVE: This study examined the relationship between behavioural inhibition, insecure mother-child attachment and evidence of anxiety in the offspring of mothers with anxiety disorders. METHOD: Twenty children aged 18 to 59 months who were born to 18 mothers with diagnosed anxiety disorders were examined for behavioural inhibition (Kagan's measures) and mother-child attachment (Strange Situation Procedure). Child anxiety was assessed using DSM-III-R criteria and the Child Behavior Checklist (CBCL). RESULTS: Sixty-five percent of the children were behaviourally inhibited. They showed more somatic problems and fewer destructive behaviours than those who were not inhibited. Eighty percent of the children were insecurely attached. They had higher CBCL internalizing scores than secure children and three of them met diagnostic criteria for anxiety disorders. CONCLUSION: Though preliminary, this work suggests a need to identify children of anxious mothers as being at risk for anxiety, especially in the presence of inhibited temperament or attachment difficulties. PMID- 7788624 TI - Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome. AB - Prolactin and cortisol responses to dl-fenfluramine challenge were examined in 11 patients with chronic fatigue syndrome and in 11 healthy controls who were age and gender matched. After obtaining two baseline samples, each subject was given 60 mg of dl-fenfluramine orally and further blood samples were drawn hourly during the following five hours in order to measure prolactin and cortisol levels. There was no difference in either baseline or fenfluramine-induced hormonal responses between patients with chronic fatigue syndrome and controls. There was also no correlation between depression scores on HAM-D and hormonal responses in patients with chronic fatigue syndrome. The findings of this study do not support a role for 5-HT in chronic fatigue syndrome. PMID- 7788625 TI - Evidence-based psychiatry. AB - OBJECTIVE: To apply the evidence-based medicine paradigm to the domain of psychiatric practice and to bring out the consequences for psychiatry of this approach in order to foster the emergence of an evidence-based psychiatry. METHODS: The basic assumptions of traditional and evidence-based paradigms, as delineated by the Evidence-Based Working Group, are used to structure an exploration of the evidence-based approach to psychiatry. Theoretical and practical issues are considered and an example of evidence-based decision making is given. RESULTS: An evidence-based approach to psychiatry is described as one that emphasizes the importance of systematic observation and the use of rules of evidence in hypothesis testing. It is suggested that psychiatrists using this approach will be in a position to provide superior patient care. DISCUSSION: The application of scientific method to psychiatric problems is discussed as the essence of an evidence-based approach. The common error of "scientism" is described. The authors identify advantages and limitations of an evidence-based approach to psychiatric practice and advocate a decision-making process that balances individualized clinical acumen (phronesis) and information derived from empirical study of groups of patients (techne). PMID- 7788626 TI - Laser angioplasty of peripheral arteries: an epilogue? AB - This review gives a short overview of the results of 15 years of experimental and clinical work on laser angioplasty. Experimentally, photothermal and photomechanical ablation of plaque could be demonstrated. However, laser angioplasty did not cause reduction of platelet adhesion and intimal hyperplasia. Clinically, the technique of laser angioplasty was continuously improved until the initial recanalization rates and long-term patency rates in femoropopliteal artery occlusions were the same as the success rates of percutaneous transluminal angioplasty (PTA). This was proven by various randomized studies. Currently, laser angioplasty cannot be proposed as a routine procedure because it is an expensive technology. However, laser recanalization and debulking of total occlusions should be further developed, especially in combination with endoluminal graft placement. PMID- 7788627 TI - Iatrogenic dissection of the celiac artery and its branches during transcatheter arterial embolization for hepatocellular carcinoma: outcome in 40 patients. AB - PURPOSE: To study the sequelae of iatrogenic dissection of the celiac axis and its branches in a large patient population. METHODS: We analyzed 40 patients with hepatocellular carcinoma (HCC) whose celiac artery or its branches were dissected during transcatheter arterial embolization (TAE) and underwent follow-up angiography within 2 months. RESULTS: The two most common sites of dissection were the celiac artery in 13 patients (32.5%) and the proper hepatic artery in 11 patients (27.5%). Follow-up angiography revealed complete recanalization in 32.5% (13/40), irregularity and narrowing of the lumen in 40% (16/40), and complete obstruction in 27.5% (11/40). Therefore, 72.5% (29/40) of the dissected arteries recanalized. Pseudoaneurysm formation of the dissected artery was observed in 32.5% (13/40). Subsequent TAE was possible via the dissected arteries in 79% (27/34) of patients in this series. CONCLUSION: Iatrogenic dissection of the celiac and proximal hepatic arteries heals spontaneously in the majority of patients, and in most instances allows subsequent TAE. PMID- 7788628 TI - Malignant biliary obstruction treated by Wallstents and Strecker tantalum stents: a retrospective review. AB - PURPOSE: To evaluate retrospectively the role and the effectiveness of self expandable Wallstents and balloon-expandable Strecker stents in patients with inoperable malignant obstruction of the biliary tree. METHODS: Fifty patients with malignant biliary obstruction were treated from August 1991 to August 1992 by percutaneous placement of 55 metallic endoprostheses (39 Wallstents, 16 Strecker stents). All patients were followed by clinical evaluation, laboratory data, and ultrasonographic examination until death. RESULTS: Wallstent placement was successful in 36 patients without procedure-related complications. One partial occlusion after 1 year was resolved by percutaneous balloon dilatation. Fourteen patients were treated with 16 Strecker stents. Stenting was unsuccessful in four cases; four occlusions (after 6 h, 48 h, 2 and 6 months) were encountered. CONCLUSION: Wallstent endoprostheses have good results and long-term patency. There were some problems with Strecker stents during the placement and there was a higher occlusion rate. PMID- 7788630 TI - Analysis of particle size generated during plaque ablation with a flashlamp pumped pulsed dye laser. AB - PURPOSE: To examine debris size generated during in vitro plaque ablation by laser energy and estimate the risk of peripheral embolization following laser angioplasty. METHODS: A flashlamp pumped pulsed dye laser of 480-nm wavelength was used to ablate calcified arteriosclerotic plaque, fibrous fatty plaque, and normal aortic wall on samples of human cadaver aortas. Each tissue sample was immersed in saline solution and treated with the same amounts of laser energy transmitted by a 320 microns-diameter glass fiber in direct tissue contact. The debris generated during plaque ablation was then separated from the supernatant and the particles were counted and analyzed for size. RESULTS: Depending on the underlying type of tissue and the setting of laser energy, a wide range of particles with sizes between 5.3 mm2 and 64 microns 2 was found in samples. The largest particles were found after ablation of calcified atherosclerotic plaque, whereas fibrous, fatty plaque and normal aortic wall showed smaller particles and a lesser amount of debris. CONCLUSION: Our study demonstrates that a considerable amount of debris is generated during laser angioplasty at 480 nm and that particle size is sufficient to cause potentially symptomatic embolic occlusions of mid- and small-sized peripheral arteries. PMID- 7788629 TI - Transcatheter arterial embolization as a method of cisplatin-retention enhancement on the VX2 tumor uterus transplants. AB - PURPOSE: Enhanced cisplatin (Pt) retention using transcatheter arterial chemoembolization (TAE) with Gelfoam particles was studied in rabbit uterine tumors. METHODS: Ten rabbit uteri were inoculated with 5 x 10(7) cells of VX2 carcinoma. Three to four weeks later cisplatin, 1 mg/kg, was injected, either with (TAE group) or without (IA group) being mixed with small Gelfoam particles, into the aortic bifurcation over 5 s. Blood and tissue concentration of cisplatin were determined. RESULTS: Slower arterial blood clearance of Pt was observed in the TAE group compared with the IA group, whereas the venous blood Pt clearance curves were similar for both groups. The uterine tumor Pt concentration at 80 min was found to be 2.52-fold higher after TAE compared with IA (p < 0.01). In the pelvic metastatic lymph nodes, the Pt concentration was 4.63 times higher after TAE than after IA (p < 0.01). CONCLUSION: These data indicate that TAE is an effective means of increasing tissue concentration in uterine tumors. PMID- 7788631 TI - Persistent iliac endarteritis with pseudoaneurysm formation following balloon expandable stent placement. AB - We present a patient who developed endarteritis and pseudoaneurysm formation complicating iliac artery stent placement. Blood cultures grew Staphylococcus aureus. Three weeks after antibiotic treatment, the aortic bifurcation and the stents were removed, together with the left common iliac artery pseudoaneurysm. As with any other implantable device, septic complications are dreaded and should be recognized and treated early. Consideration may be given to the use of appropriate prophylactic antibiotics. PMID- 7788632 TI - Chronic aortoiliac dissection treated by self-expanding stent placement. AB - A 47-year old male patient presented with claudication from a right-sided aortoiliac dissection secondary to transfemoral cardiac angiography. Placement of two self-expanding stents led to immediate compression of the false channel. The patient has been free of symptoms for 18 months. PMID- 7788633 TI - Percutaneous hepatic venous reanastomosis in a patient with Budd-Chiari syndrome. AB - A 33-year-old woman with Budd-Chiari syndrome for 9 years presented with worsening right upper quadrant pain and progressive liver dysfunction. Hepatic venography demonstrated hepatic vein occlusions, without significant IVC obstruction. Attempts at stenting a stenotic middle hepatic vein were unsuccessful. Transjugular access, however, allowed puncture from the stump of the right hepatic vein into the engorged right intrahepatic vein that had been demonstrated by retrograde hepatic venography. Two Palmaz stents were used to form the veno-venous reanastomosis. Initial success was documented angiographically and by pressure measurements before and after shunting. Followup at 7 and 16 months confirmed patency of the anastomosis without intimal hyperplasia. The patient noted near-complete resolution of her pain, and her liver function stabilized. PMID- 7788634 TI - A new use of the Simpson percutaneous atherectomy catheter: resection of retained valve cusps of an in-situ vein graft. AB - An in-situ saphenous vein graft occluded because of retained valve cusps. After aspiration thrombectomy, percutaneous transluminal balloon angioplasty was performed, but reocclusion occurred 11 months later. Following a second aspiration thrombectomy, the restenosed retained cusps were resected using the Simpson percutaneous atherectomy catheter. The graft remained patent until the patient's death from unrelated causes 6 months later. PMID- 7788635 TI - Wallstent misplacement into the paraumbilical vein during TIPS from the left hepatic vein: correction by placing a second stent through the mesh of the first stent. AB - During a TIPS procedure using the left hepatic vein approach, a Wallstent was misplaced into a dilated paraumbilical vein instead of the left portal vein. The correct shunt direction from the left portal vein to the left hepatic vein was restored by coaxially inserting a second Wallstent through the stretched mesh of the misplaced stent. To prevent such stent misplacement, it seems useful to emphasize the importance of maintaining the exchange guidewire within the distal portion of the splenic or mesenteric vein throughout dilatation and stenting of the liver parenchyma. PMID- 7788636 TI - Embolization of a ruptured middle colic artery aneurysm. AB - Middle colic artery aneurysms are very uncommon. A few cases of occlusion of superior mesenteric artery aneurysms without bowel ischemia are reported. We describe successful uncomplicated embolization of a ruptured middle colic artery aneurysm with a Gelfoam plug. PMID- 7788637 TI - Percutaneous retrieval of a surgical laparotomy sponge from the peritoneal cavity. AB - Percutaneous retrieval of an extravascular foreign body is an uncommon procedure. This report describes the successful retrieval of a 46 x 46-cm laparotomy sponge from the peritoneal cavity using a Nitinol Gooseneck Snare system. This technique can eliminate the need for exploratory surgery and may be particularly useful in poor operative candidates. PMID- 7788638 TI - Use of a cutting balloon for dilatation of a resistant venous stenosis of a hemodialysis fistula. AB - In a 71-year-old patient with a Brescia-Cimino hemodialysis fistula, high pressure balloon dilatation failed to open the stenosis completely and a constant waist of the balloon was found. The use of a 3.5-mm coronary cutting balloon (Barath balloon) was helpful in preparing the stenosis for subsequent successful dilatation. PMID- 7788639 TI - Hemiazygos continuation of a left inferior vena cava draining into the right atrium via persistent left superior vena cava: demonstration by helical computed tomography. AB - We report an unusual case of hemiazygos continuation of a left inferior vena cava draining into the right atrium via the persistent superior vena cava. Spiral computed tomography (CT) showed the course and the flow direction of this vena caval anomaly in a real-time manner, obviating conventional venography. PMID- 7788640 TI - Effect of ionophores on the processing of the beta-amyloid precursor protein in different cell lines. AB - 1. Alzheimer's disease is characterized by the deposition in the brain of extracellular amyloid plaques and vascular deposits consisting mostly of amyloid beta-peptide (A beta). A beta, a polypeptide of 39-43 amino acids (M(r), approximately 4 kDa), is derived proteolytically from a family of proteins of 695 770 amino acids (M(r), approximately 110-140 kDa) called beta-amyloid precursor protein (beta APP). 2. beta APP, an integral membrane glycoprotein, is extensively posttranslationally modified within the endoplasmic reticulum (ER) and various Golgi compartments. beta APP is cleaved by proteases in either the trans-Golgi network or the post-Golgi apparatus and then secreted as a truncated soluble form into the conditioned media of cultured cells and cerebrospinal fluid samples from human subjects. beta APP can be processed either by an antiamyloidogenic secretory pathway or by an endosomal/lysosomal pathway. 3. I studied the effect of two ionophores on the processing of beta APP in cultured cells. Monensin and, in some cases, ammonium chloride increase the intracellular accumulation of beta APP in several cell lines and may alter its processing. Monensin, which had the most consistent effects, also inhibited secretion of beta APP in a differentiated (growth factor mediated) cell line. Nigericin, with greater K+ selectivity, was less able to alter the accumulation and possible processing of the protein. 4. These results suggest that the increase in the accumulation of intracellular beta APP observed after treating cells with ionophores has some specificity. The selective effect of these ionophores on the metabolism of beta APP may provide a model system to analyze the pathways for studying maturation, secretion, and degradation of beta APP. PMID- 7788641 TI - Concomitant protein phosphorylation and endogenous acetylcholine release induced by nicotine: dependency on neuronal nicotinic receptors and desensitization. AB - 1. Nicotine stimulated two Ca(2+)-dependent processes in rat frontal cortex synaptosomes: the phosphorylation of an 80-kDa protein band and the release of endogenous ACh.3 Both effects were mediated by neuronal nAChRs and coincided with depolarization of the synaptosomal plasma membrane induced by the drug. Changes in the state of phosphorylation of the 80-kDa band (presumed to contain synapsin I) were correlated with changes in the release of ACh as follows, from 2 to 4. 2. Blockade of predominant, nerve terminal P-type Ca2+ channels with omega-agatoxin IVA, did not prevent nicotine from stimulating ACh release. In contrast, exposure to the toxin partially inhibited the release promoted by the depolarizing agent veratridine and attenuated protein phosphorylation induced by either nicotine or veratridine. Taken together, these data suggest that, upon nicotine stimulation. Ca2+ enters nerve terminals through two distinct pathways. The first, via Ca2+ channels, is necessary (but not sufficient) for both nicotine-induced phosphorylation and ACh release. The second, both necessary and sufficient for nicotine-induced phosphorylation and release, is the neuronal nAChR itself. 3. Preincubation of the synaptosomes with a subeffective concentration of nicotine inactivated both nicotine-induced ACh liberation and phosphorylation. This shows that diminished release is associated to decreased phosphorylation of the 80-kDa protein band, most likely as a consequence of nicotine-promoted nAChR desensitization. 4. Augmented ACh release and phosphorylation of the 80-kDa protein band were achieved by using the protein phosphatase inhibitor okadaic acid. However, okadaic acid did not summate with either nicotine or veratridine to increase ACh release further. This is probably because okadaic acid, as in other neurons, increases intracellular Ca2+ (Cholewinski et al., 1993), thus promoting desensitization of ACh release. PMID- 7788642 TI - Selective postmortem degradation of inducible heat shock protein 70 (hsp70) mRNAs in rat brain. AB - 1. Altered mRNA levels in postmortem brain tissue from persons with Alzheimer's disease (AD) or other neurological diseases are usually presumed to be characteristic of the disease state, even though both agonal state (the physiological state immediately premortem) and postmortem interval (PMI) (the time between death and harvesting the tissue) have the potential to affect levels of mRNAs measured in postmortem tissue. Although the possible effect of postmortem interval on mRNA levels has been more carefully evaluated than that of agonal state, many studies assume that all mRNAs have similar rates of degradation postmortem. 2. To determine the postmortem stability of inducible heat shock protein 70 (hsp70) mRNAs, themselves unstable in vivo at normal body temperature, rats were heat shocked in order to induce synthesis of the hsp70 mRNAs. hsp70 mRNA levels in cerebellum and cortex were then compared to those of their heat shock cognate 70 (hsc70) mRNAs, as well as to levels of 18S rRNAs, at 0 and at 24 hr postmortem. 3. Quantiation of northern blots after hybridization with an hsp70 mRNA-specific oligo probe indicated a massive loss of hsp70 mRNA signal in RNAs isolated from 24-hr postmortem brains; quantitation by slot-blot hybridization was 5- to 15-fold more efficient. Even using the latter technique, hsp70 mRNA levels were reduced by 59% in 24-hr-postmortem cerebellum and by 78% in cortex compared to mRNA levels in the same region of 0-hr-postmortem brain. There was little reduction postmortem in levels of the hsp70 mRNAs or of 18S rRNAs in either brain region. 4. In situ hybridization analysis indicated that hsp70 mRNAs were less abundant in all major classes of cerebellar cells after 24 hr postmortem and mRNAs had degraded severalfold more rapidly in neurons than in glia. There was no corresponding loss of intracellular 18S rRNA in any cell type. 5. We conclude from these results that the effect of postmortem interval on mRNA degradation must be carefully evaluated when analyzing levels of inducible hsp70 mRNAs, and perhaps other short-lived mRNAs, in human brain. PMID- 7788644 TI - Midazolam and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-7 phosphonoheptanoic acid (AP-7) attenuate stress-induced expression of c-fos mRNA in the dentate gyrus. AB - 1. The effects of restraint stress on c-fos mRNA expression in the dentate gyrus were investigated by in situ hybridization. 2. Confirming previous findings, c fos mRNA expression increased after 30 min of forced restraint. 3. This effect was attenuated by a previous i.c.v. injection of the anxiolytic benzodiazepine midazolam (20 nmol/2 microliters) or the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP-7; 5 nmol/2 microliters). 4. These results suggest that the dentate gyrus is activated during restraint stress and that this activation may be modulated by benzodiazepine gamma-aminobutyric acidA (GABAA) or NMDA receptors. PMID- 7788643 TI - Heterogeneity and differential expression of the gamma-aminobutyric acidA (GABAA)/benzodiazepine receptor in the avian brain during development. AB - 1. The changes in the GABAA/benzodiazepine receptor in chicken brain during development has been studied by using 3H-flunitrazepam as the probe for the benzodiazepine modulator site and the antibodies recognizing the receptor protein. In the telencephalon and optic tectum, the proteins of 48, 50, and 51 kD were markedly labeled by 3H-flunitrazepam from embryonic day 18 to postnatal days, as revealed by photoaffinity labeling and SDS-PAGE of the brain membranes; the 51-kD protein appeared to be the predominant one in labeling intensity except at embryonic day 18 and postnatal days 14 and 28, whereas the 47- and 50-kD proteins were dominant in the cerebellum. However, the 47- and 48-kD proteins were faintly seen after postnatal day 28 in the three regions examined. 2. Immunoblotting using a monoclonal antibody against the 50- and 51-kD proteins showed that the straining pattern in the developing telecephalon or optic tectum was similar to the 50 kD/51 kD pattern obtained from fluorography. The antibody also stained the 50- and 51-kD proteins in the cerebellum despite the fact that the 51-kD protein was barely seen in the fluorogram. Moreover, the 50-kD protein was recognized by an antiserum raised against a partial sequence of the alpha 1 subunit of the receptor expressed in bacteria. The staining levels for the 50-kd protein by the antiserum on immunoblots of the brain regions were low in embryonic animals but higher during postnatal stages, consistent with that seen in fluorograms. 3. Receptor binding autoradiography using 3H-flunitrazepam exhibited that varying degrees of labeling intensity occurred among various brain areas at different ages. High densities of binding were present in the olfactory bulb, paleostriatum, optic tectum, and midbrain. These results support the diversity of the GABAA/benzodiazepine receptor in the vertebrate CNS. PMID- 7788646 TI - [Free radicals in the pathogenesis of selected diseases]. AB - Free radicals are chemical substances which contain one or more unpaired electrons, which is the cause of their high reactivity with a series of biologically important substances such as fatty acids, DNA, RNA, amino acids. The source of radicals are immunological reactions and reactions in the endoplasmatic reticulum during detoxication of xenobiotics. Free radicals can act on the organism by a number of reactions, the most frequent on being lipid peroxidation when important toxic products are formed such as 4-hydroxy 2,3 trans-nonenal (4 HNE) and malondialdehyde. Direct assessment of free radicals due to their short life span is difficult in clinical practice. The majority of measurements is based on the assessment of substances which are formed by the reaction of free radicals in the organism. The most frequent method is assessment by means of thiobarbituric acid. Oxidative stress (the reaction produced by the action of free radicals) of tissues and cells is caused by the increased formation of free radicals and/or reduced capacity of antioxidant systems. Free radicals are involved in the process of ageing, cancerogenesis, inflammatory and degenerative diseases, atherogenesis, and play a part in the ischaemic and toxic damage of the organism. During evolution antioxidant defence mechanisms developed which under physiological conditions are sufficient to inactivate free radicals. Antioxidant systems can be divided into two groups--antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase etc) and antioxidant substrates (tocopherols, carotenoids, ascorbic acid, glutathione, transferrin, ceruloplasmin etc). PMID- 7788647 TI - [The role of central catecholamines and dopaminergic receptors in the development of estrogen-induced adenohypophyseal hypertrophy]. AB - Estrogens and thyroid hormones contribute importantly to cell proliferation and tumor transformation in the pituitary gland. The purpose of the present article is provide review about neurotransmitters, chemicals, and receptors that are involved in estrogen-induced anterior pituitary growth. Central dopaminergic and noradrenergic systems are thought to be the most important systems in regulation of pituitary growth and function. For this purpose authors discuss some of their past and present data suggesting that estrogen-induced anterior pituitary pituitary growth is associated with decreased synthesis and metabolism of central catecholamines and increased adenohypophyseal dopamine 2 receptors. Treatment with thyroid hormones prevents both estrogen-induced catecholaminergic inhibition and dopamine D2 receptor increment in the anterior pituitary gland. Further studies focusing on central catecholaminergic systems, pituitary receptor equipment and mechanisms of intracellular signal transduction will be of value to better understand pituitary tumor formation and possibly to find new approaches toward treating patients with these tumors. PMID- 7788645 TI - Developmental changes in the brain-stem serotonergic nuclei of teleost fish and neural plasticity. AB - 1. During early ontogeny, the serotonergic neurons in the brain stem of the three spined stickleback shows a temporal and spatial developmental pattern that closely resembles that of amniotes. 2. However, in the adult fish, only the midline nuclei of the rostral group (dorsal and median raphe nuclei) and the dorsal lateral tegmental nucleus are consistently serotonin-immunoreactive (5 HTir), whereas the groups of the upper and lower rhombencephalon (raphe pontis, raphe magnus, and raphe pallidus/obscurus nuclei) are variable and, when present, contain relatively small numbers of 5-HTir neurons. 3. Using specific antisera against tryptophan 5-hydroxylase and aromatic L-amino acid decarboxylase, we have shown that the lateral B9 group and the groups of the upper and lower rhombencephalon are consistently present in adult sticklebacks. The results are discussed in relation to other known instances of neurotransmitter plasticity or transient neurotransmitter expression in teleost fish. 4. While there are several instances of transient expression of neurotransmitter markers by discrete neuronal populations, there is so far no evidence of changes from one neurotransmitter phenotype to another in the brain of teleost fish. However, there are indications of plasticity of expression of catecholamines and indoleamines, and their respective synthesizing enzymes, as reflected in age dependent changes and variation between individuals of different physiological status. 5. As the brain grows continuously in teleost fish, and new neurons are added from proliferative regions, synaptic connections may be expected to undergo remodeling in all brain regions throughout life. Thus, the teleostean brain may be considered a suitable model for experimental studies of different aspects of neural plasticity. PMID- 7788648 TI - [DNA cytometry analysis in childhood tumors]. AB - BACKGROUND: DNA contents in cells may be determined by flow cytometry. The relationship between malignant cell aneuploidy and prognosis is known in many types of neoplasms in adults and in children. In some situations, demonstration of an aneuploid clone verifies presence of malignant cells. Aneuploidy is rare in benign diseases. This report summarizes our first experiences with cytometric DNA analysis and shows the method's abilities to other potential users. METHODS AND RESULTS: We investigated DNA contents in blood and bone marrow (BM) specimens of 25 children with leukemia, in 41 unfixed solid tumors after biopsy and in 24 specimens of paraffin embedded neuroblastoma tissue. We also investigated 5 specimens of cerebrospinal fluid (CSF) of patients with medulloblastoma, 18 specimens of CSF from patients with leukemia or lymphoma, 4 pleural exudates suspected from malignancies, and 45 specimens of possibly infiltrated BM from primary solid tumors. As the purpose of this study was to test the method on a relatively small number of specimens, we did not perform statistical analysis of our data. As reported previously, aneuploidy was frequent in CALLA + acute lymphoblastic leukemia and in types of neuroblastoma with favorable prognosis (lower clinical stages and less than 2 years of age). CONCLUSIONS: Our results show that DNA ploidy may be tested by flow cytometry in an easy and fast way. The source of the material may be unfixed tumors, deparaffinized tumors, BM, blood, CSF and pleural exudates. PMID- 7788649 TI - [Decrease in common carotid artery intimal thickness after hypolipemic therapy]. AB - BACKGROUND: In recent years evidence was provided that it is possible to assess sonographically the thickness of the intima of the common carotid artery, whereby an increase of the thickness of the intima is considered an early stage of atherosclerosis. In the submitted work the authors tried to assess whether it is possible to influence the thickness of the intima by therapy. METHOD AND RESULTS: In 32 patients with familial hyperlipoproteinaemia sonographic control examinations of the common carotid artery were performed after 27 months of comprehensive treatment. In 21 subjects with familial hypercholesterolaemia the thickness of the intima decreased from 0.83 mm to 0.68 mm (p < 0.01), in 8 subjects with familial combined hyperlipoproteinaemia from 0.77 mm to 0.74 mm (a decline was recorded in half the subjects). In the whole group the greatest decrease was recorded in subjects treated with statins and a smaller decrease in those treated with fibrates. CONCLUSIONS: The authors assume that the decrease of the thickness of the intima of the common carotid artery recorded in hyperlipoproteinaemic patients after hypolipidaemic treatment is a manifestation of regression of atherosclerosis. PMID- 7788650 TI - [Simvastatin in the treatment of familial hypercholesterolemia]. AB - BACKGROUND: The association between hypercholesterolemia and premature atherosclerosis is almost universally accepted. Treatment of hyperlipoproteinemias represents a reasonable approach in preventive cardiology. The aim of the study was to prove a hypolipidemic effect of simvastatin, Zocor tablets a 10 mg, produced by MSD, U:S.A. in patients with familial hypercholesterolemia. METHODS AND RESULTS: 29 familial hypercholesterolemia heterozygotes have been treated with increasing dose of simvastatin (10 and 20 mg/day with the evening meal) for three months. All patients have been on AHA step I diet. The basic parameters of lipid and lipoprotein metabolism have been measured, as well the concentrations of apolipoproteins A-I and B, and the level of lipoprotein(a). Concentration of total cholesterol decreased after treatment with 10 and 20 mg of simvastatin by 20%, resp. 26%. The hypolipidemic effect was even more pronounced in LDL-cholesterol level, which was reduced by 24% respectively 34%. On the other hand therapy with simvastatin did not influence HDL-cholesterol at all. Also triglycerides concentration did not changed very significantly after administration of simvastatin (triglycerides levels were reduced by 7% respectively by 18%). Decline of LDL-cholesterol has been accompanied by decrease of apolipoprotein B concentration by 24%, resp. 26%. The concentration of lipoprotein (a) has not been statistically significantly influenced, even its level increased slightly. The body weight of the patients did not changed during the study. Simvastatin treatment has been well tolerated by the patients. CONCLUSIONS: Simvastatin, Zocor, seems to be powerful hypolipidemic drug, which is to be used even in the treatment of familial hypercholesterolemia heterozygotes, who are usually very resistant to the therapy. The dose of 10 mg of simvastatin is usually sufficient to influence plasma lipids and lipoproteins. A double dose intensifies the hypolipidemic effect but this additional effect is not so expressive. Zocor is tolerated well by the patients and in safety laboratory we did not notice any important undesirable result. PMID- 7788651 TI - [The human genome--chromosome 10 and the collagen genes]. AB - In relation to locuses of the 10th chromosome at present the following are in the focus of interest: tumours of endocrine glands, medullary carcinoma of the thyroid gland (MTC) and multiple endocrine neoplasias (MEN). It seems that the unifying basis is the oncogene RET, responsible for the development of Hirschsprung's disease HSCR. The authors mentions also metabolically important locuses for choline acetyltransferase (CHAT), uriporphyrinogen synthase (UROS) and methyl guanine methyltransferase (MGMT). A special paragraph is devoted to a list of collagenous genes COL1-COL18 and diseases associated with them. PMID- 7788652 TI - [Introductory remarks on the problem of the battered, abused and neglected child syndrome]. PMID- 7788654 TI - [Aspects of genealogy of the use of force on children]. AB - The quality of the parent-child relationship and the contents of the concept of childhood cannot be separated from the general social situation. The understanding of the child world and its perception of as equivalent to the world of adults is associated as an integral part with humanization and spiritual advances of civilization and depends on the economic standard of society and our ability to understand the spiritual heritage of our civilization. There exists still a deeply rooted mechanism where many families under conditions of stress (social, economic etc.) ventilate their tension and aggressiveness on the child. Battering and abuse of children (except for pathological personality of the parent) is an atavistic remnant of the perception of childhood as a period of incompetence of the individual. The basic manifestations shifted, however, from the transparent and socially tolerated victim of the child to the present--latent and hidden refined "victim" which tortures the child in particular from the mental and emotional aspect. Today we no longer sacrifice the child but much more frequently his childhood. Because of his physical weakness and mental lability even today children are still considered a suitable object for ventilating aggression, temptation to abuse power. In addition to refuting any abuse, battering and neglect of children it must be admitted that this "socially unacceptable behaviour" is encountered less than formerly. An important role is also played by the economic and cultural standard of society. Similarly as certain economic prerequisites are necessary for democracy, economic conditions play an important part in an emancipated concept of childhood and empathic upbringing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788653 TI - [The battered, abused and neglected child and the Crisis Center for Children]. AB - The syndrome of the battered, abused and neglected child is becoming manifest also in our country with increasing frequency and severity, not only because much more attention is paid to it than ever before. Our system of child care and protection is, however, by far not yet ready to resolve this serious problem in the life of children, families and society as a whole and therefore ways and means must be sought how to face it, how to recognize it, treat it and in particular how to prevent it. One of the important means how to tackle this dangerous social phenomenon is a specialized department concerned in a comprehensive way on an interdisciplinary basis, with skilled and effective clinical work with every single abused child and its family in close association with all disciplines and institutions interested in the problem as well as by conceptual work, research, training and expert opinions etc. The crisis centre for children in Prague 4-Michle wants to serve with its experience and findings as a model workplace for building special institutions within the framework of a rational, interdisciplinary network of child care and protection in this country. The results of its two-year work and the great interest in it on the part of many localities and regions justify its efforts. PMID- 7788655 TI - [Prevention of child abuse]. AB - The concept of "child abuse" comprises as a rule physical damage, neglect of the child and sexual abuse of the child. Prevention in the widest sense of the word comprises all three negative social phenomena-in the narrower sense of the word it has for every phenomenon its specific goals, procedures and means. Greatest attention must be paid to primary prevention. The latter has several layers, above all purposeful enlightenment of the public and extensive measures for the benefit of families with children, secondly training and education of primary educators of the child, and thirdly detection of so-called risk groups of the population. From the aspect of prevention we have to take into account the potential risk on the part of the children as well as risk situations in life encountered by children and adults. PMID- 7788656 TI - [Diagnosis and therapy of child sexual abuse]. AB - In the crisis centre for children cases of force used on children cumulate, incl. sexually abused children. The interdisciplinary team of the centre is faced with the task to diagnose and treat this phenomenon and with the protection of the child from possible further damage (secondary victimization). In the submitted paper the author analyzes the period from October 1992 to the middle of September 1994, using uniform indicators. Special attention is devoted to psychic and somatic symptoms of the sexually abused child. PMID- 7788657 TI - [Causes of death in fatal cases of child abuse 1964-1988]. AB - BACKGROUND: Abuse and/or neglect of children can lead not only to serious health damage but in extreme cases to death. A lethal outcome in the abused child is an incomplete group of seriously damaged children; it, however, makes possible not only numerical comparison but also assessment of trends. The objective of the present work was an analysis of deaths of children who died in conjunction with the use of force in the family. METHODS AND RESULTS: The author analyzed a group of 75 children, 47 boys (63%) and 28 girls (37%) aged less than five years: it covers the period of 25 years (1964-1988) and administrative area of the capital of Prague and former Central Bohemian region with a total number of 2 million population. Newborn babies killed by the mother during delivery or immediately after delivery (63 subjects) were not included in the group. According to analysis by age the following number of deaths was recorded in different groups: 0-1 year 45 deaths (60%), 1-2 years 13, 2-3 years 11, 3-4 years similarly as 4-5 years 3 deaths each. The ratio of boys:girls was 47:28. The most frequent cause of death were head injuries (31-41%), followed by suffocation 15x, injury of abdominal organs 6x, intoxications (4x, incl. 3x carbon monoxide), multiple injuries 4x, injuries of thoracic organis 3x, starvation 2x, hypothermia 2x, thermal damage 1x. The findings on necropsy are not useful only for assessing the cause of death, the mechanism of damage and the time when the damage was inflicted but the spectrum of types of damage can help clinical and social workers in the prevention of the battered child syndrome. CONCLUSIONS: Child abuse and neglect in families can lead not only to serious health damage but it can be also fatal. In an area with a population of 2 millions in the course of 1964-1988 75 deaths of children aged less than five years were recorded (ratio: 2.5:1 million per year). Mechanical injuries predominate (89%) in particular head injuries (41%). PMID- 7788658 TI - [2 years' activity of the Crisis Center for Children in the care of battered, abused and neglected children]. AB - The crisis centre for children in Prague 4-Michle was established as the first workplace to resolve problems of battered, abused and neglected children. Its main task is clinical work with thus suffering children, based above all on a comprehensive, interdisciplinary approach in diagnosis, therapy and rehabilitation and also prevention of this adverse phenomenon in the population. In the course of two years 502 cases were dealt with (on average with 3-4 clients) during 2814 consultations. Most frequently physical and mental abuse was encountered (40%), gross neglect in 17.5% and sexual abuse (in 10%-with a marked relative increase between the first and second year of the activities of the centre). Other problems of child suffering for various reasons (psychiatric or other diseases of the parents, handicapped child, child running away from family etc.) in 32.5%. In addition to clinical work the centre tries to generalize its findings, train workers interested in the above problems, participate in the concept of care of battered children and its implementation in this country. PMID- 7788659 TI - [Munchausen syndrome]. AB - The authors present their own observation of five child patients with Munchhausen's syndrome and Munchausen's syndrome by proxy resp. Both these units are included in the wider framework of the syndrome of the battered child. Four boys and one girl are involved, aged 12-16 years. In all instances the reason for admission to hospital was macroscopic haematuria. The children were prior to hospitalization subjected to a series of various invasive examinations, incl. repeated examinations under anaesthesia to elucodate the cause of macroscopic haematuria. The uncommon course of the "disease" and results of the examinations led in four of the five children to suspicion of Munchhausen's syndrome. Based on this suspicion after immobilization of the patients associated with prevention of manipulation with the hands, macroscopic haematuria disappeared as well as haematuria in general. In the fifth patient Munchhausen's syndrome by proxy was involved. The patient was referred because of repeated attacks of macroscopic haematuria a renal biopsy. The authors analyze in more details the individual case-histories and in the conclusion to they raise their objections to the opinion that these two syndromes are extremely rare. PMID- 7788660 TI - [Problems in placing the abused child in foster home care]. AB - Children for whom foster parents are found include also abused and battered children. Is such a child able to establish a satisfactory emotional relationship with the foster parents or adoptive parents? The case of a boy repeatedly exposed to cruel corporal punishment in the original family. Attempts of the law court to return the child from a children's home to the original family. Finally complete refusal of the boy by his own parents. Placement of the boy in a new family and his successful adaptation in the new environment. PMID- 7788661 TI - [The human genome--chromosome 11]. AB - The eleventh human chromosome is one of the most intensely studied and as regards the number of known genes it holds the third place after chromosomes 1 and X. The best known ones located on it are e.g. loci of the beta-globulin family which are associated with the best known and most widely distributed molecular disease sickle-cell anaemia and beta-thalassaemia. From knowledge of the causes of these diseases at the genome level so-called DNA diagnostics are derived which can be applied also to the prenatal period. On chromosome 11 are the loci of two complementary groups (C, D) which are extremely sensitive to ionizing radiation- ataxia teleangiectasia, the proinsulin locus the mutations of which, however, are not the cause of common types of diabetes. Development of the urogenital tract as indicated by some of its disorders (WAGR, Denys-Drash syndrome) is controlled by WT genes. PMID- 7788662 TI - [Pulse therapy in diffuse connective tissue diseases]. AB - Methods of i.v. pulsed treatment using methyl prednisolone, cyclophosphamide or polyvalent immunoglobulin made it possible to suppress rapidly and effectively the activity of prognostically serious (clinical and laboratory) manifestations in diffuse connective tissue diseases (systemic autoimmune diseases). The author presents a general justification of this therapeutic method with emphasis on the immunogenetics of pathological autoimmunity (autogenes, apoptosis), he describes methodical aspects, the asset and partial clinical indications in rheumatoid arthritis, systemic lupus erythematosus, polymyositis and dermatomyositis, and primary systemic vasculitis. The author mentions also prerequisites of further development of i.v. pulsed treatment in diffuse connective tissue diseases. PMID- 7788663 TI - More recent trends in infant and child mortality in Zimbabwe and possible explanations. AB - The paper uses published results from the 1992 census to describe more recent trends in infant and child mortality in Zimbabwe. It is shown that the period 1986 to 1988 provided the turning point in the gradual decline in infant and child mortality in the provinces. After this period, several provinces experienced a slow-down in mortality decline while some even experienced reversals. Using correlation analysis, it was suggested that the factors which affected infant mortality could be the same ones affecting child mortality. The paper then proceeds to formulate hypotheses on possible explanations for the slow down in mortality decline. PMID- 7788664 TI - Organophosphate exposure in pesticide formulation and packaging factories in Harare, Zimbabwe. AB - A cross sectional study was conducted in September 1989 in order to estimate the prevalence of organophosphate exposure and to identify factors associated with increased organophosphate exposure in pesticide producing factories in Harare, Zimbabwe. Sixty five workers entered the study with 45 of them providing blood specimens. The mean cholinesterase level was 75.3 pc (standard deviation 21.07 pc). Twenty (44.4 pc) workers had cholinesterase levels of less than 75 pc. The workers had adequate knowledge (75 pc+) of the importance of protective devices but had less knowledge of about 50 pc of health effects of pesticides. Smoking (t = 3.49; degrees of freedom (df) = 43; p < 0.01) and eating (t = 2.14; df = 43; p < 0.05) at work place were associated with increased exposure to organophosphate. The number of symptoms was not correlated with cholinesterase levels (Spearman's rank correlation coefficient--0.70; p = 0.12). We conclude that a significant number of workers were exposed to organophosphate. Increased personal hygiene such as washing hands before eating or smoking should reduce the amount of exposure. PMID- 7788665 TI - Hydatidiform mole: a study of 40 patients admitted at Harare Central Hospital, Zimbabwe. AB - Hydatidiform mole contributes to a significant numbers of hospital admissions at Harare Hospital. The characteristics, diagnosis, management and follow up of the women with molor pregnancy admitted to Harare Hospital are presented. The follow up of these women was grossly inadequate. PMID- 7788666 TI - Plasma levels of retinol, ascorbic acid and alpha-tocopherol in sickle cell anaemia. AB - The plasma concentrations of the antioxidant vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) were determined in sickle cell anaemia (SCA). It was found that the concentrations of ascorbic acid and alpha-tocopherol were significantly depressed while that of retinol was only slightly reduced. The depletion in the levels of these antioxidant vitamins may account for some of the observed manifestations of SCA such as increased susceptibility to infection and haemolysis. PMID- 7788667 TI - Non-traumatic spinal cord diseases in Ibadan, Nigeria: aetiology and prognostic factors. AB - In this hospital based study, we analysed the clinical records of 104 patients having various spinal cord diseases seen between 1988 and 1993 with a view to delineating diagnostic and prognostic features. The patients comprised 80 males and 24 females with a mean age of 45 years. The mean duration of disease at presentation was 11 months and the average duration of stay in hospital was five months. Spondylotic myelopathy (31 subjects) predominated. It showed cervical predilection, infrequent sphincteric dysfunction and low ESR. Tuberculous disease of the spine (26 subjects) was next in frequency. The presentation of the TB cases was similar to those of neoplastic causes but the latter had a worse prognosis. There was a predilection for the dorsal spine and a high ESR. Myelitis occurred in the younger age group, showed dorsal spine predilection and relatively low ESR. The prognostic factors include duration of disease at entry, duration of hospital stay, presence of complication, motor power above grade three and absence of flacidity. The preventable causes of death include: deep vein thrombosis with subsequent pulmonary embolism and septicaemia. PMID- 7788668 TI - Acute bacterial meningitis in Enugu, Nigeria. 1 April 1989 to 31 March 1993. AB - A total of 84 cases of meningitis confirmed by isolation of the organisms at the University of Nigeria Hospital (UNTH) Enugu, Nigeria between 1 April 1989 and 31 March 1993 are presented. The cases are analysed by diagnosis, seasonal distribution, age and sex distribution and age specific case fatality rate. The most common type of meningitis was pneumococcal meningitis 32 cases, followed by coliform meningitis 31 cases and meningococcal meningitis, six cases. Other bacterial causes of meningitis accounted for 15 cases. The majority of cases occurred in infants, followed by children, with all cases occurring sporadically. Mortality was high with Streptococcus pneumoniae having the highest case fatality rate of 28.13 pc followed by coliforms, 25.78 pc. Fifty pc of the patients had pre-medication before presentation at the hospital, and many of the patients could not receive appropriate therapy because they were unable to afford the cost of the drugs. This probably contributed to the high mortality. PMID- 7788669 TI - Haemophilia in northern Nigeria. AB - Thirteen patients from 11 families were diagnosed as cases of haemophilia A or B during 1977 to 1984. The majority presented with post circumcisional bleeding. Cryoprecipitate and packed red cells were used in the management. Haemophilia and other inherited bleeding disorders are not as rare as otherwise assumed. This is the first report from Northern Nigeria. PMID- 7788671 TI - A Zimbabwean approach to a Zimbabwean problem. PMID- 7788670 TI - Three consecutive ipsilateral tubal pregnancies in a nulliparous African woman: the role of conservative treatment. AB - A very rare case of three consecutive ipsilateral tubal pregnancies, in a 31 year old nulliparous Malawian woman is presented. The three pregnancies occurred over a four year period between 1989 and 1993, and were treated at three different hospitals in Malawi and Britain. The first two were treated conservatively by "milking" the ectopic out in Malawi and Britain respectively while the third was treated by partial salpingectomy in Malawi. All three were confirmed clinically, ultrasonographically, at surgery and histopathologically. The rarity of such a condition, the role and value of conservative treatment of tubal pregnancy in Africa, especially in the light of the probable aetiological and/or predisposing factors are discussed. PMID- 7788672 TI - Medical audit in Zimbabwe in 1898. PMID- 7788673 TI - Legal aspects of medical research and the way forward. AB - The main thrust of this article is to examine critically the laws and ethics governing medical research in this country--Zimbabwe. The article is divided into two parts. The first part starts with an introduction which highlights the need for medical research and the hazards related thereto. This is followed by stating the general legal position aimed at controlling medical research, the emphasis being on law, the international codes of medical ethics intended to fill the wide gaps not covered by our legislations and individual ethical considerations. The other topics covered in the first part include confidentiality in research and compensation for those who suffer injuries while undergoing a clinical trial. The second part covers the following topics; informed consent, stressing on the need for informed consent from both adults and children when carrying out medical research; embryo research and researchers carried out by n'angas and finally the conclusion suggesting the need to re-examine laws relating to medical research in this country which seem to be wholly inadequate. In brief the article is intended to stimulate more public debate on the law relating to medical research. For example a question is often asked: Does the law adequately protect those who carry out medical research and conversely those upon whom medical research (or clinical trials) is done? PMID- 7788674 TI - Neonatal haematology in Zimbabwe. II: The red cell and white cell parameters. AB - Red cell and white cell parameters were determined in 600 (310 male and 290 female) normal Black Zimbabwean neonates with a mean +/- sd birth weight of 3.0 +/- 0.4 (range 2.04 to 4.50, median 3.0) kg using a Coulter Counter Model S Plus. Cord anaemia (cord Hb < 13.5 gdl-1) was detected in 60 (10 pc) of the neonates. Although the male babies were significantly heavier than the females (p = 0.004), there were no significant differences (p > 0.05) in the red cell and white cell indices between the two sexes. When the haematological parameters of the 540 (90 pc) non-anaemic (cord Hb > or = 13.5 gdl-1) neonates were analysed, the mean +/- sd values which may serve as local reference standards were: Hb 15.2 +/- 1.8 (range 13.5 to 19.4) gdl-1, Hct 47.3 4.9 (range 38.6 to 60.3) pc, MCV 107.8 +/- 9.4 (range 88.8 to 134.3) fl, MCH 31.9 +/- 3.4 (range 25.2 to 45.2) pg, MCHC 32.9 +/- 1.3 (range 30.0 to 38.3) gdl-1, nucleated red blood cells 6.1 +/- 5.9 (range 0 to 55) per 100 white blood cells, reticulocyte count 5.0 +/- 1.9 (range 0 to 24.0) pc, total leucocyte count 13.8 +/- 4.4 (range 4.6 to 132.8) x 10(9)l-1; differential count: neutrophils 7.30 +/- 2.90 (range 1.72 to 18.02) x 10(9) l-1, lymphocytes 5.67 +/- 2.47 (range 0.98 to 16.14) x 10(9) l-1, monocytes 0.81 +/- 0.83 (range 0 to 5.58) x 10(9) l-1, 1 and eosinophils 0.08 +/- 0.13 (range 0 to 0.72) x 10(9)l-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788675 TI - In vitro activity of several antimicrobial agents against Neisseria gonorrhoeae and comparison of cost of treatment. AB - During a cross sectional study on the prevalence and incidence of gonorrhoea, Neisseria gonorrhoeae was isolated from 185 people aged between 16 and 60 years. In vitro activity of six antimicrobial antibacterial agents, penicillin, erythromycin, tetracycline, cotrimoxazole, ceftriaxone and norfloxacin on the isolated N. gonorrhoeae were carried out. The results obtained showed that, of all 111 isolates, 48 (43.2 pc) were penicillinase producing N. gonorrhoeae (PPNG) and 63 (56.8 pc) were non PPNGs. Over 90 pc of both PPNG and non PPNG isolates were sensitive to tetracyline and erythromycin. Seventy five pc of the PPNG and 45 pc non-PPNG were not sensitive to two units of penicillin. Both PPNG and non PPNG were less sensitive to cotrimoxazole 25 micrograms. Norfloxacin and ceftriaxone were over 70 pc effective but were extremely expensive for most people who got infected. PMID- 7788676 TI - Splenic and hepatic trauma: a three year review. AB - We present a three year study of 22 consecutive patients treated for splenic and liver injuries at Mpilo Central Hospital between 1988 and 1990. A total of eight patients died giving an overall mortality rate of 36 pc. There was no mortality recorded in nine patients (41 pc) treated for splenic injuries. However, of the nine patients (41 pc) treated for liver injuries four patients died giving a mortality rate of 44 pc in this group. The highest mortality rate was recorded in the group of patients with both splenic and liver injuries because these injuries were invariably associated with other severe multiple injuries. We admitted four patients (18 pc) in this group and they all died. PMID- 7788677 TI - Prevalence of Campylobacter enteritis in children from Yaounde (Cameroon). AB - A cross sectional study on the prevalence of Campylobacter jejuni/coli and its possible aetiologic role in childhood diarrhoea in Yaounde was undertaken in 272 children presenting with diarrhoea and 157 age matched controls from April 1989 to October 1990. Stool cultures were performed according to standard techniques for Campylobacter jejuni/coli shigella and salmonella species. Rotavirus was detected using a latex agglutination test. Campylobacter jejuni/coli was isolated from 21 (7,7 pc) of 272 patients with diarrhoea and five of 157 (3,2 pc) controls (p > 0.05), all aged zero to four years old. Shigella and salmonella species were cultured from 2,2 pc and 1,1 pc of 272 patients respectively while rotavirus antigen was detected in 19,6 pc of 204 patients. Twenty eight pc of children with Campylobacter enteritis were exposed to chickens while 23,8 regularly drank water from streams which probably were contaminated. Our results indicate a high prevalence of campylobacter enteritis in children living in Yaounde and also suggest that a high rate of carriage of Campylobacter jejuni/coli could exist in children zero to four years without diarrhoeal illness. to four years without diarrhoeal illness. PMID- 7788678 TI - Appendicitis in south eastern Nigerian children. AB - One hundred and sixty nine cases of acute appendicitis were seen among 760 children aged to zero to 15 years treated for a variety of acute abdominal emergencies in the University of Calabar Teaching Hospital (UCTH), Calabar, during the period January 1982 to 1991. This condition ranks second among cases of acute abdominal emergencies in this group of patients. Those aged 13 to 15 years formed the majority (59 pc) of the children undergoing appendicectomy. As is the experience of other authors, appendicitis is rare under the age of three years. A female preponderance is observed in our study with a male: female ratio of 1:1,6 in contrast to reports elsewhere. The reason for this reversal is not clear. Parasitic infestation due to Ascaris lumbricoides involved 3 pc of our cases. This may be of significance in the aetiology of this disease. Despite the long delay in surgical intervention, no death was reported. Complications such as gangrene and perforation with peritonitis were recorded in only 8 pc of the patients. This favourable outcome despite a delay in initiating treatment may be related to self-medication with antimicrobials before reporting to the hospital. PMID- 7788679 TI - A case of psychotic mood disorder in an AIDS patient. AB - The following case is reported not because it is uncommon, but rather because cases like it will become more common as the AIDS endemic in sub-Saharan Africa progresses. This is a case of a young woman previously undiagnosed as being HIV positive who was admitted to a psychiatric unit. She clinically presented with a manic episode. The case is remarkable in that it demonstrates the complicated differential diagnosis that needs to be considered in evaluating immune compromised patients who present primarily with disturbances of mood, cognition, or behaviour. PMID- 7788680 TI - A community based investigation of causes of maternal mortality in rural and urban Zimbabwe. Maternal Mortality Study Group. AB - Most data on maternal mortality in Zimbabwe has been urban hospital based. Using a network of informants and sensitized health workers an attempt was made to identify and investigate all maternal deaths in rural Masvingo and urban Harare over a two year period. The present report discusses place of death and the medical causes in both populations. Results gave maternal mortality rates of 168 and 85 per 100,000 live births for Masvingo and Harare respectively. These rates are significantly higher than those from conventional reporting systems especially in the rural area where 27 pc of deaths occurred at home or in transit. The leading medical causes of death were haemorrhage in Masvingo (25 pc of deaths) and eclampsia in Harare (26 pc), with puerperal and post abortal sepsis as the next most common causes in both cases. Malaria featured as the major indirect cause in Masvingo (7.6 pc). There were four suicides committed following unwanted pregnancy. The rural/urban variation in causation of death is discussed and the study results compared with other community based studies internationally. SYNOPSIS: This community based study revealed higher maternal mortality rates (MMR) than conventional statistics, especially in the rural area where deaths occurred at home or in transit. In the rural area the MMR was higher and the leading cause of death was haemorrhage, compared to eclampsia in the urban area. Strategies to reduce maternal deaths should include factors both within and outside health service structures. PMID- 7788681 TI - Who are the Zimbabwean loop users? The social and demographic characteristics of Zimbabwean IUCD users. AB - As part of a study into the reasons for the low utilization of the intra-uterine contraceptive device (IUCD) among Zimbabwean women, a records' review of IUCD users over the period 1985 to 1989 was carried out. A 10 pc sample of the records of women inserted over this period was taken. This paper reports on the social demographic and selected screening characteristics of these women. A total of 1,179 records were reviewed. The IUCD users had a higher socio-economic status than the Zimbabwean population as a whole. Nearly 20 pc of the IUCD users were professional, technical and related workers, (mostly nurses and teachers), compared to 4.3 pc among the general population. Clients had apparently better reproductive histories than the population as a whole, probably reflecting their socio-economic status and possibly the screening process. The women were in their mid to late twenties in age at the time of insertion, and had been married an average of nine years. A quarter of the clients did not want any more children. They were using the IUCD to suspend their conception indefinitely after completion of their families. About 74 pc of the women had learnt about the family planning clinic from the local clinic/nurses or the community based distributor, indicating the importance of these sources of information. Eighty pc of the women were previous acceptors of modern contraceptives, but only 6 pc had apparently used the IUCD before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788682 TI - Effects of ACE inhibition on left ventricular dimensions and haemodynamics in systemic hypertension: a radionuclide and echocardiographic study. AB - The aim of this study was to assess the effects of Angiotensin Converting Enzyme (ACE) inhibition on cardiac systolic and diastolic parameters and left ventricular muscle mass in hypertensive patients. For this purpose 30 patients (22 female and eight male) with mild to moderate essential hypertension, aged 47 +/- 2 years, were treated with enalapril maleate (MK 421, an ACE inhibitor) for six weeks. They underwent M-mode and Doppler echocardiography and radionuclide ventriculography at the beginning and after six weeks of enalapril treatment. In this study all patients treated with the ACE inhibitor enalapril responded with a significant decrease in mean arterial pressure (p < 0.001). A significant reduction in left ventricle and mass index were shown after six weeks of treatment with enalapril (p < 0.01). Total peripheral resistance and end-systolic stress decreased in the same time course (p < 0.001). Ejection fraction increased in both examinations after six weeks of therapy with enalapril, but this increase was not statistically significant. In radionuclide examinations, time to peak filling rate decreased significantly after six weeks of enalapril therapy (p < 0.02). Despite these improvements in cardiac systolic and diastolic parameters, cardiac output and stroke volume decreased slightly after enalapril treatment. We concluded that enalapril improves diastolic and systolic parameters in LV function but causes slight decreases in cardiac output and stroke volume in addition to lowering blood pressure. PMID- 7788683 TI - Effect of Plasmodium falciparum malaria on plasma fibrinopeptide-A (FpA) concentration. AB - Plasma Fibrinopeptide-A (FpA) concentrations were determined using Enzyme-linked Immunosorbent Assay (ELISA) in patients with acute Plasmodium falciparum malaria infection and in 30 healthy controls. The mean FpA levels of the malaria patients were significantly raised (p < 0.001). The patients' FpA level correlated positively with malaria parasitaemia, but negatively with plasma fibrinogen concentration. A week after commencement of chloroquine therapy and subsequent disappearance of malaria parasites from the thick blood films, the patients' FpA levels decreased significantly from pre-treatment values. It is suggested that the elevated FpA and reduced plasma fibrinogen levels in the patients probably indicate a more widespread existence of overt coagulation defect in acute malaria infection. PMID- 7788684 TI - Legal article II: legal aspects of medical research and the way forward. PMID- 7788685 TI - Antimicrobial susceptibilities of Shigella dysenteriae type 1 isolated in Zimbabwe--implications for the management of dysentery. AB - Shigella dysenteriae type 1 was cultured from 56/170 (33 pc) rectal swab specimens collected from patients presenting to hospitals in Harare, Zimbabwe with dysentery. All of the isolates were resistant in vitro to trimethoprim sulfamethoxazole, with MICs > 32 mg/l, and all except one were resistant to ampicillin, most with an MIC > 256 mg/l. One isolate was resistant to nalidixic acid (MIC > 256 mg/l), but all of the others were sensitive, most with an MIC of 2 mg/l or less. Using antibiotic disks, 96 pc isolates were resistant to chloromphenicol and 94 pc to tetracycline. All isolates were sensitive in vitro to gentamicin. On the basis of these findings, we suggest that commonly available antibiotics including ampicillin, cotrimoxazole, chloramphenicol or tetracycline should not be used for the treatment of dysentery. The most appropriate antimicrobial agent at the present time would be nalidixic acid. Resistance to this is, however, likely to emerge and data on susceptibilities to fluoroquinolones as well as to cephalosporins should be obtained so that further recommendations can be given timeously. PMID- 7788686 TI - Preliminary laboratory trial of Neem on anopheles and culex larvae in Zambia. PMID- 7788687 TI - Prolonged urokinase infusion for chronic total native coronary occlusions: clinical, angiographic, and treatment observations. AB - Prolonged intravascular infusion of urokinase has proven beneficial in reestablishing patency of chronically occluded peripheral arteries and saphenous vein grafts. This study was performed to assess the efficacy and safety of prolonged urokinase infusion as a prelude to angioplasty in chronically occluded native coronary arteries, that had failed standard angioplasty techniques. Twenty five patients with objective evidence for ischemia in the distribution of a chronic coronary occlusion were referred for percutaneous intervention. Patients were assessed for any potential exclusions from lytic therapy. Urokinase infusion through both a SOS wire and a stable guiding catheter was continued at 100,000 240,000 units/hr for 8-25 hr; patients then underwent attempted balloon angioplasty. Mean duration of urokinase infusion was 20.6 +/- 7.7 hr (total dose 163,000 +/- 52,447 units/hr). Fibrinogen levels dropped slightly with this (300 +/- 129 to 203 +/- 81 mg/dl, P = 0.02). Angiography posturokinase showed improvement in 7 (28%) with regard to coronary flow (> or = 1 TIMI-grade). Angioplasty was successful in 13 (52%), with final angiographic result revealing thrombus in 5 (20%), or dissection 8 (32%). The infusions were well-tolerated with a low incidence of chest pain, 2 (8%) or ischemic ECG response, 2 (8%); myocardial infarction, 2 (8%); or significant bleeding 2 (8%). All patients survived the procedure, with a length-of-hospital stay = 5.1 +/- 4 days. Use of prolonged preangioplasty intracoronary urokinase infusion can be done safely with success in roughly one-half of patients with chronic total native coronary occlusions who have failed prior attempts at percutaneous intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788688 TI - Transluminal extraction catheter for the treatment of diseased saphenous vein grafts: a multicenter experience. AB - To evaluate the efficacy, safety, and long-term results of atherectomy using the Transluminal Extraction catheter (TEC), patients with diseased saphenous vein grafts were enrolled in a prospective nonrandomized trial. Patients were followed to hospital discharge for acute complications and underwent routine 6-mo reevaluation with repeat cardiac catheterization to assess restenosis. Atherectomy was performed on 650 graft lesions in 538 consecutive patients (male 81%; mean age 66 yr; range 37-81). Mean graft age was 8.3 yr; (range 0.3-20) with 85% of grafts > 3 yr of age. Complex lesion morphology included thrombus (28%), ulceration (13%), and eccentricity (50%). Lesion success was achieved in 606 lesions (93%) with clinical success in 479 patients (89%). Lesion success was achieved in 90% of thrombus containing lesions, 97% of ulcerated lesions, and 97% of grafts > 3 yr. Complications included nonfatal myocardial infarction in 4 (0.7%) of patients, emergency bypass surgery in 2 (0.41%), and in-hospital death in 17 patients (3.2%). Angiographic follow-up at 6 mo was obtained from 268 lesions in 227 patients. The overall lesion angiographic restenosis rate was 60%. TEC atherectomy can be performed in patients with diseased saphenous vein grafts with high primary success and low complication rates. It is suitable for use in aged grafts, particularly in the presence of thrombus and ulcerations, and may be superior to balloon angioplasty alone in this group of patients. PMID- 7788689 TI - Stenting with the half (disarticulated) Palmaz-Schatz stent. AB - A total of 110 half (disarticulated) Palmaz-Schatz coronary stents were implanted in 102 patients. Procedural success rate was 98%. Elective stenting was performed in five patients. The others received half stents for bail-out situations, including short dissections, relapsing stenoses, dissections not adequately covered by a full stent, ostial stenoses, and thrombus containing lesions. Seventeen patients received no anticoagulation except aspirin. Complications included one procedural death, three acute occlusions (resulting in one Q and two non-Q wave myocardial infarctions), and one non-Q wave infarction related to side branch closure. Stenting with the half Plamaz-Schatz coronary stent is an effective technique. It allows stenting in situations where a full stent may not be ideally suited. Use of only half a stent reduces thrombogenicity and halves costs. PMID- 7788691 TI - Percutaneous transradial coronary Palmaz-Schatz stent implantation, guided by intravascular ultrasound. AB - Intravascular ultrasound (IVUS) allows accurate assessment of stent deployment, its use being confined to the use of 8 French (F) guiding catheters. We evaluated the feasibility of combining transradial artery Palmaz-Schatz stent implantation through 6F guiding catheters with IVUS for assessment of stent diameter after delivery at moderate inflation pressures (10-12 atmospheres [atm]) with compliant balloons and after high pressure dilatations with balloons of intermediate compliance. In 8 consecutive patients, 12 stents were delivered with Scimed Express balloon catheters at 10-12 atm followed by IVUS (EndoSonics CathScanner; Visions FX 3.5F 20 MHz transducer). An ultrasound study was repeated after high pressure dilatations (16-20 atm) with Schneider Magical Speedy balloon catheters. The balloon diameters were derived from manufacturer provided specifications. In all patients the transducer could easily be advanced through the guiding catheters. Reference diameter of the stented segment was 3.7 +/- 0.5 mm (2.7-4.5) and the diameter of Scimed Express balloons during inflation was 4.0 +/- 0.3 mm (3.6-4.7). Stent diameter was 3.0 +/- 0.1 mm (2.8-3.2) (P < 0.001 compared to the reference and the balloon diameter). The diameter of the Schneider Magical Speedy balloons at secondary dilatations with 16 +/- 3 atm (14-20) was 4.1 +/- 0.4 mm (3.3-4.5) (P = 0.50 compared to the initial balloon diameter). Final stent diameter was 3.3 +/- 0.4 mm (2.9-4.1) (P = 0.02 compared to the initial stent diameter). All stents were symmetrically deployed and well apposed. No damage to vessel or stents was detected after passage of the transducer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788692 TI - Coronary stenting without anticoagulation. AB - Stents are useful bail-out devices in coronary angioplasty. They are also used electively for situations associated with poor angioplasty results (e.g., restenotic lesions, venous grafts) and may reduce restenosis rates. However, the significant incidence of stent thrombosis necessitated aggressive anticoagulation with associated hemorrhagic complications. This remains a major limitation of stenting. We present our experience of stenting with half (disarticulated) Palmaz Schatz coronary stents in eight consecutive patients, managed with aspirin alone. No patient experienced acute or subacute stent thrombosis. PMID- 7788690 TI - Emergency endoluminal stenting for abrupt vessel closure following coronary angioplasty: a randomized comparison of the Wiktor and Palmaz-Schatz stents. AB - In order to compare the efficacy of two different stent types in case of bailout stenting, 65 patients, with abrupt or threatened vessel closure following coronary angioplasty, were randomly assigned to either Wiktor (Medtronic Inc., Minneapolis, MN, 33 patients) or Palmaz-Schatz (Johnson & Johnson Interventional, Warren, NJ, 32 patients) stent implantation. Stenting was technically feasible in all except one patient and immediately successful in reverting ischemia and vessel closure in 60 patients (92%). At hospital discharge, complication rates were comparable: early vessel closure, 18% (Wiktor) versus 13% (Palmaz-Schatz) (P = 0.53); any clinical event (such as death, myocardial infarction, and surgical revascularization): 18% (Wiktor) versus 22% (Palmaz-Schatz) (P = 0.71). At 6 months follow-up, these complication rates remained equal: restenosis, 38% (Wiktor) versus 27% (Palmaz-Schatz) (P = 0.42); any clinical and angiographic (vessel closure and restenosis) event: 45% (Wiktor) and 41% (Palmaz-Schatz) (P = 0.69). Baseline, direct postprocedural, and follow-up quantitative coronary analysis data were similar, with, however, an exception for the postprocedural residual stenosis [28% (24-32%) (Wiktor) and 21% (18-23%) (Palmaz-Schatz] (means and 95% confidence intervals). In conclusion, despite a discrete postprocedural angiographic benefit observed with the Palmaz-Schatz stent, the long-term clinical and angiographic outcome is similar in both treatment groups. The choice whether to implant a Wiktor or Palmaz-Schatz stent may probably be left to the discretion of the operator and his experience with one particular device. PMID- 7788693 TI - Coronary artery stenting for acute closure complicating primary angioplasty for acute myocardial infarction. PMID- 7788694 TI - Treatment of acute stent thrombosis with local urokinase therapy using catheter based, drug delivery systems: a case report. AB - Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63-yr-old white female initially underwent successful placement of a Palmaz-Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase-coated hydrogel balloon (Hydro Plus). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no-reflow. Local urokinase delivery directly to the site of thrombus with catheter-based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re-establishing coronary flow in the setting of acute stent thrombosis. PMID- 7788695 TI - Sequential implantation of dissimilar tandem stents for long dissections complicating percutaneous transluminal coronary angioplasty. AB - Acute closure remains a significant complication of percutaneous angioplasty, and coronary artery stenting serves as a useful bail-out device. We describe two cases of sequential implantation of dissimilar tandem stents, a Gianturco-Roubin (4 x 20mm) stent and a Palmaz-Schatz (4 x 15mm) stent, for long dissection complicating percutaneous transluminal coronary angioplasty. PMID- 7788696 TI - Retrieval of occluding unexpanded Palmaz-Schatz stent from a saphenous aorto coronary vein graft. AB - The Palmaz-Schatz coronary stent is used frequently to reduce the rate of restenosis of balloon angioplasty in saphenous vein grafts. In many European centers, the stent, manually crimped on a balloon, is advanced across the stenosis without a protective sheath. This report describes a patient in whom an attempt to deploy a stent in the orifice of a saphenous vein graft was complicated by dislodgement of the unexpanded stent from the balloon. The unexpanded stent caused immediate occlusion of the vein graft and severe ischemic symptoms. The stent was retrieved by inflation of another balloon in the graft, distal to the stent, pulling the balloon toward the guiding catheter, and then withdrawing the whole system. PMID- 7788697 TI - Successful transcatheter management of Palmaz Stent embolization after superior vena cava stenting. AB - A 34-year-old patient with benign superior vena cava syndrome (SVCS) was treated with thrombolytic therapy, balloon angioplasty, and placement of two peripheral Palmaz stents. Embolization of one stent to the right atrium occurred 10 min after successful implantation. This serious complication was successfully managed by percutaneous transcatheter technique with retrieval from the right atrium and subsequent deployment into the right external iliac vein of the lost stent. Complete resolution of SVCS symptoms occurred within 24 hr and moderate superior vena cava restenosis was successfully dilated 8 months later. At 12-month follow up the patient continues to be asymptomatic. PMID- 7788698 TI - Collateral flow velocity alterations in the supply and receiving coronary arteries during angioplasty for total coronary occlusion. AB - The unique observations of contralateral and ipsilateral coronary artery collateral supply before and after angioplasty suggest highly responsive conduits to hemodynamic conditions. The study of collateral supply system is not only significant for our current understanding of the dynamic behavior of the collateral circulation, but may also have important clinical implications for the treatment of patients with a chronic coronary occlusion. PMID- 7788699 TI - Effect of data compression on quantitative coronary measurements. AB - Digital coronary and left ventricular angiography demand high transfer rates and very large data storage if all the clinical data are to be achieved. If appropriate compression schemes were available without compromising the quality and resolution of the image data, such demands could be lessened. In this study we compared the influence of different compression factors of the Adaptive Real Time Image Compression (ARTIC) scheme used on the Philips DCI-SX systems on coronary measurements assessed with the Automated Coronary Analysis (ACA) package. Loss-free acquired images of size 512(2) x 8 bits, which had been stored digitally on tape, were reloaded into the DCI with compression factors of 2, 3, and 4; only the factor 2 is loss free. To evaluate the effect of the different data compressions on the accuracy of the measurements, the diameters of a vessel phantom (tube sizes ranging from 0.687 to 5.062 mm) were determined. To evaluate the reproducibility of the results, the intraobserver variability was determined for the different compression factors from 40 coronary obstructions. The differences in the reference diameter measurements of the vessel phantom were 0.03 +/- 0.06 mm, 0.01 +/- 0.07 mm, and 0.04 +/- 0.08 mm for the compression factors 2 (loss free), 3, and 4, respectively. The results were not statistically significantly different. The intraobserver variabilities in the obstruction diameter measurements of the coronary obstructions were -0.04 +/- 0.13 mm, 0.00 +/- 0.14 mm, and 0.02 +/- 0.13 mm for the compression factors 2, 3 and 4, respectively. The intraobserver variabilities in the reference diameter measurements were -0.02 +/- 0.12 mm, 0.01 +/- 0.09 mm, and 0.03 +/- 0.09 mm for the compression factors 2, 3, and 4, respectively. The intraobserver variabilities of the percent diameter stenosis were 0.96 +/- 4.19%, -0.01 +/- 4.88% and -0.04 +/- 4.68% for the compression factors 2, 3, and 4, respectively. None of these differences were statistically significant. Both from a qualitative and quantitative point of view, data compression factors 3 and 4 are acceptable in digital coronary arteriography. PMID- 7788700 TI - Caution in use of beta blockers during pregnancy. PMID- 7788701 TI - Terumo Glidewire: the wire of choice for chronic total occlusion. PMID- 7788702 TI - Unstable angina pectoris associated with Imitrex therapy. PMID- 7788703 TI - Stents: reenforcement to the interventionalist. PMID- 7788705 TI - [Nomenclature and classification of membrane receptors and their subtypes]. AB - Present rapid growth of information about receptors for endogenous ligands and drugs requires changes in definitions, nomenclature and classifications of receptors and their subtypes. Receptors are defined as such membrane structures for which we have sufficiently reliable characterization of their structure, transducing mechanisms (mediation of intracellular effects), and selectively acting drugs (operational criterion). This characterization is based on the integrated approach to classification that relies on all three essential criteria. The current classification of membrane receptors is organized by International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). Their conclusions about receptor classifications are regularly published in pharmacological journals and in special publications. List of presently known membrane receptors and their subtypes is provided in this review. PMID- 7788706 TI - [Adrenergic receptors--nomenclature and classification of the types and subtypes]. AB - The purpose of this review is to present current knowledge regarding adrenergic receptors and their subtypes. These receptors belong to the superfamily of structures with seven transmembrane domains. They are coupled with G-regulatory proteins. Similarly to other membrane receptors, their division is based on three criteria: structural, transductional, and operational. At present, adrenergic receptors are divided into three main groups, depicted as alpha 1, alpha 2 a beta receptors. Receptors alpha 1 and alpha 2 are further divided into additional 4 subtypes, which are marked with upper case subscripts A-D. Receptors beta are subdivided into three types, marked with subscripts 1-3. Classification of adrenergic receptors can be considered as a prototype for classification of other membrane receptors. The significance of all known receptors subtypes is not yet known. Multiple subtypes of adrenergic and also other receptor types exist simultaneously not only in one tissue but also frequently in a single cell where they can exert both synergistic as well as antagonistic effects. The discovery of functions and interactions of individual receptor subtypes represents a big challenge for future studies. Introduction of new selective agonists and antagonists not only helps to classify various receptor subtypes but it also has a big therapeutic potential. PMID- 7788704 TI - Systemic anaphylactoid reactions to iodinated contrast media during cardiac catheterization procedures: guidelines for prevention, diagnosis, and treatment. Laboratory Performance Standards Committee of the Society for Cardiac Angiography and Interventions. AB - This report represents the first guidelines for prevention, diagnosis, and treatment of anaphylactoid reactions to contrast media occurring specifically during cardiac catheterization. The incidence of contrast media complications in the catheterization laboratory is 0.23% with 1 death per 55,000. Anaphylactoid reactions are nonimmune mediated, but histamine release and other mediators produce a clinical presentation indistinguishable from anaphylaxis. In patients with known previous reactions, pretreatment with steroids and diphenhydramine and the use of nonionic contrast media have significantly reduced the potential of recurrent reaction. Minor reactions such as limited urticaria may be watched for progression or treatment with diphenhydramine, whereas more serious reactions such as angioedema or laryngeal edema require airway stability and ephinephrine administration. Shock should be vigorously treated simultaneously with intravenous epinephrine and large volumes of normal saline. If the patient can be stabilized, the study should be completed as histamine, leukotrienes, and other vasoactive products should be relatively depleted. PMID- 7788707 TI - [Do the kidneys play an important role in the pathogenesis of "essential" hypertension?]. AB - The Prague Hypertensive Rat (PHR) is a model of genetic hypertension derived from the Wistar strain, in which a normotensive parallel, the Prague Normotensive Rat (PNR), was also bred from the same parent pair. Thus, it is possible to transfer organs between both parallels without signs of rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy and transplantation of one kidney within the PHR and PNR groups did not affect the systolic blood pressure (SBP). Transplantation of one kidney from PNR to a bilateral nephrectomized (BNX) PHR normalized the high SBP; and transplantation of one kidney from PHR to BNX PNR led to an elevation of SBP: hypertension "travels" with the kidney. When the development of high SBP in PHR was prevented for 2 months after weaning by antihypertensive drugs, transplantation of one kidney from these rats to BNX PNR always induced a sustained hypertension in the recipient. If a PHR was left with one original kidney in situ after transplantation of a "normotensive" kidney, the high blood pressure persisted until the original "hypertensive" kidney was removed. These results support the view that the kidney of PHR produces a "hypertensinogenic" substance, the secretion of which is genetically determined and is not influenced by the magnitude of the SBP. PMID- 7788708 TI - [The carotid body--mechanisms of hypoxia sensing]. AB - The carotid body is a peripheral chemoreceptor monitoring arterial blood gas tension and pH and contributing to the regulation of breathing. The molecular mechanism of oxygen sensing is unknown. However, it is hypothesised that lowering of arterial oxygen tension detected by O2 sensitive K+ channels, evokes a selective inhibition of K+ current of glomus cells, with an increase of cellular excitability. Hydrogen peroxide production within the glomus cells may serve as a messenger which regulates potasium channels or gene expression. PMID- 7788712 TI - Interactions among mutations affecting spontaneous mutation, mitotic recombination, and DNA repair in yeast. AB - The mutant alleles mms9-1, mms13-1, or mms21-1 of Saccharomyces cerevisiae confer pleiotropic effects, including sensitivity to the alkylating agent methyl methanesulfonate, elevations in spontaneous mutation and mitotic recombination, defects in meiosis, and cross-sensitivity to radiation. We constructed double mutant strains containing an mms mutation and a defect in either excision repair, mutagenic repair, or recombinational repair and measured the levels of spontaneous mutation and mitotic recombination. Double mutants lacking excision repair show elevations in spontaneous mutation but with predominantly unchanged levels of mitotic recombination. RAD52 function was required for the expression of the hyper-recombination phenotype of the mms9-1, mms13-1, and mms21-1 alleles; double mutants displayed the very low recombination levels characteristic of rad52 mutants. Phenotypes of double mutants containing one of the mms alleles and either of the hyper-recombination/mutator rad6-1 or rad3-102 alleles suggest that the mutagenic lesions in mms strains may not be identical to the recombinogenic lesions. PMID- 7788714 TI - Molecular cloning of Rab-related genes in the yeast Yarrowia lipolytica. Analysis of RYL1, an essential gene encoding a SEC4 homologue. AB - Small GTP-binding proteins of the Rab family are involved in the vesicular traffic inside eukaryotic cells. A gene library from the yeast Yarrowia lipolytica was screened with an oligonucleotide deduced from a highly conserved sequence in the Rab family. Four different genes were isolated. One of them, RYL1, was shown to be essential for cell viability. RYL1p displayed a high similarity with and tight phylogenetic relationships to SEC4p. When placed under the control of the GAL10 promoter, RYL1 was able to specifically relieve the thermosensitivity of a sec4-8 mutant of Saccharomyces cerevisiae. Therefore, it is proposed that RYL1 is a functional homologue of the S. cerevisiae SEC4 gene and is involved in the fusion of secretory vesicles with the plasma membrane in the general protein secretion pathway. PMID- 7788713 TI - Control of glucose influx into glycolysis and pleiotropic effects studied in different isogenic sets of Saccharomyces cerevisiae mutants in trehalose biosynthesis. AB - The GGS1/TPS1 gene of the yeast Saccharomyces cerevisiae encodes the trehalose-6 phosphate synthase subunit of the trehalose synthase complex. Mutants defective in GGS1/TPS1 have been isolated repeatedly and they showed variable pleiotropic phenotypes, in particular with respect to trehalose content, ability to grow on fermentable sugars, glucose-induced signaling and sporulation capacity. We have introduced the fdp1, cif1, byp1 and glc6 alleles and the ggs1/tps1 deletion into three different wild-type strains, M5, SP1 and W303-1A. This set of strains will aid further studies on the molecular basis of the complex pleiotropic phenotypes of ggs1/tps1 mutants. The phenotypes conferred by specific alleles were clearly dependent on the genetic background and also differed for some of the alleles. Our results show that the lethality caused by single gene deletion in one genetic background can become undetectable in another background. The sporulation defect of ggs1/tps1 diploids was neither due to a deficiency in G1 arrest, nor to the inability to accumulate trehalose. Ggs1/tps1 delta mutants were very sensitive to glucose and fructose, even in the presence of a 100-fold higher galactose concentration. Fifty-percent inhibition occurred at concentrations similar to the Km values of glucose and fructose transport. The inhibitory effect of glucose in the presence of a large excess of galactose argues against an overactive glycolytic flux as the cause of the growth defect. Deletion of genes of the glucose carrier family shifted the 50% growth inhibition to higher sugar concentrations. This finding allows for a novel approach to estimate the relevance of the many putative glucose carrier genes in S. cerevisiae. We also show that the GGS1/TPS1 gene product is not only required for the transition from respirative to fermentative metabolism but continuously during logarithmic growth on glucose, in spite of the absence of trehalose under such conditions. PMID- 7788715 TI - Molecular genetic properties of the yeast Torulaspora pretoriensis: characterization of chromosomal DNA and genetic transformation by Saccharomyces cerevisiae-based plasmids. AB - Chromosomal DNA banding patterns were obtained for three strains of Torulaspora pretoriensis by contour-clamped homogeneous-electric-field gel electrophoresis. Chromosomes were resolved into six or seven bands in the range of 800 to 2000 kb, and a polymorphism of these lengths was observed. By Southern-blot analysis, the three strains were shown to lack the DNA sequences homologous to the URA3, LEU2, TRP1, and HO genes of Saccharomyces cerevisiae. A uracil auxotrophic mutant derived from T. pretoriensis was transformed with three plasmids (YEp24, YRpHI, and YCp50) carrying the URA3 gene of S. cerevisiae by the lithium acetate method. PMID- 7788716 TI - Expression cloning, purification and characterization of a beta-1,4-galactanase from Aspergillus aculeatus. AB - Expression cloning has been used to isolate a cDNA encoding beta-1,4-galactanase from the filamentous fungus Aspergillus aculeatus. A cDNA library was prepared from mycelia, inserted in a yeast expression vector and transformed into Saccharomyces cerevisiae. Thirteen clones secreting galactanase activity were identified from a screening of approximately 2.5 x 10(4) yeast colonies. All clones expressed transcripts of the same galactanase gene. The cDNA was re-cloned in an Aspergillus expression vector and transformed into Aspergillus oryzae. The recombinant enzyme had a molecular weight of 44,000 Da, an isoelectric point of pH 2.85, a pH optimum of pH 4.0-4.5, and a temperature optimum of 45-65 degrees C, which is similar to values obtained for a beta-1,4-galactanase purified from A. aculeatus. The enzyme degraded unsubstituted galactan to galactose and galactobiose. The deduced primary sequence of the enzyme showed no apparent homology to any known enzyme, in accordance with this being the first reported beta-1,4-galactanase cDNA. However, the deduced amino-acid sequence of a Bacillus circulans DNA sequence containing an open reading frame (ORF) with no known function, showed 36% identity and 60% similarity to the galactanase amino-acid sequence. PMID- 7788717 TI - Sequence analysis of the Aspergillus nidulans pectate lyase pelA gene and evidence for binding of promoter regions to CREA, a regulator of carbon catabolite repression. AB - The nucleic acid and deduced amino-acid sequences of the pectate lyase gene (pelA) from Aspergillus nidulans are presented. The pelA gene contains two short introns, 68 and 49 bp in length, and encodes a peptide of 326 amino acids. Five transcriptional start sites are clustered between 65 and 79 bp upstream of the start codon as determined by primer extension. Comparison of the amino-acid sequences of pectate or pectin lyases from bacteria, fungi and plants revealed less than 30% overall identity. However, five regions within these enzymes, in particular domains associated with the active site, are highly conserved with amino-acid similarities greater than 50%. Phylogenetic analysis using the principle of parsimony (PAUP 3.1.1) showed that pelA is most closely related to pectate lyases from plants rather than pectin lyases from other fungi. Previously, pelA was shown to be induced by polygalacturonic acid and repressed in the presence of preferred carbon sources, such as glucose. Gel mobility shift analysis indicates that a PstI-SphI fragment from the pelA promoter binds to a fusion protein composed of the N-terminal part of CREA, a protein involved in carbon catabolite repression, and glutathione-S-transferase. This result suggests CREA may contribute to the regulation of pelA expression. PMID- 7788718 TI - Molecular cloning and analysis of nre, the major nitrogen regulatory gene of Penicillium chrysogenum. AB - We have isolated the Penicillium chrysogenum nre gene which is homologous to the major nitrogen regulatory genes areA from Aspergillus nidulans and nit-2 from Neurospora crassa. Overall, nre shows 60% identity to areA and 30% identity to nit-2 at the amino-acid level. The gene encodes a protein of 835 amino-acid residues and contains a single Cys2/Cys2-type zinc finger with an adjacent basic region and a putative acidic activation region. In the DNA-binding domain, 98% of the amino-acid residues are identical in nre, areA and nit-2. The nre gene has been shown to be functional in N. crassa by heterologous complementation of a nit 2 mutant. Growth tests indicated that transformants could utilize nitrate, amino acids, purines and amides as sole nitrogen sources. Nitrate reductase activity assays performed with transformants demonstrated that nitrogen control was completely normal. Complementation of N. crassa nit-2 mutants with 5'-deletion clones of nre suggests the possible presence of an internal promoter within the coding region. Northern analysis and ribonuclease protection assays of total cellular RNA indicated that nre encodes a 3.2-kb transcript which is reduced in content under conditions of nitrogen repression. PMID- 7788719 TI - Molecular cloning and sequence analysis of the scpZ gene encoding the serine carboxypeptidase of Absidia zychae. AB - Carboxypeptidase Z is a serine carboxypeptidase secreted by Absidia zychae NRIC 1199. The cDNA and genomic DNA carrying the scpZ gene encoding carboxypeptidase Z were cloned and sequenced. The nucleotide sequences of the cDNA (1.4 kb) and the genomic DNA (3.3 kb) were analyzed and the intervening sequences were located by a comparison of the two. It was found that the scpZ gene was interrupted by 11 short introns, 50-75 nucleotides in length. Genomic Southern analysis showed that there was only one scpZ gene in the genome of A. zychae. The gene encoded a putative pre-pro-enzyme composed of 409 amino-acid residues of the mature carboxypeptidase Z (M(r) 45,421) and an additional N-terminal sequence of 51 amino-acid residues. The amino-acid sequence around the active serine residue of carboxypeptidase Z (-G-E-S-Y-G-G-) differed from the consensus (-G-E-S-Y-A-G-) which is conserved in most of the serine carboxypeptidases so far analyzed. PMID- 7788720 TI - A group-I intron in the mitochondrial small subunit ribosomal RNA gene of Sclerotinia sclerotiorum. AB - A 1,380-bp intervening sequence within the mitochondrial small subunit ribosomal RNA (mt SSU rRNA) gene of the fungus Sclerotinia sclerotiorum has been sequenced and identified as a group-I intron. This is the first report of an intron in the mt SSU rRNA gene. The intron shows close similarity in secondary structure to the subgroup-IC2 introns from Podospora (ND3i1, ND5i2, and COIi5) and Neurospora (ND5i1). The intron has an open reading frame (ORF) that encodes a putative protein of 420 amino acids which contains two copies of the LAGLI-DADG motif. The ORF belongs to a family of ORFs identified in Podospora (ND3i1, ND4Li1, ND4Li2, ND5i2, and COIi5) and Neurospora (ND5i1). The putative 420-aa polypeptide is also similar to a site-specific endonuclease in the chloroplast large subunit ribosomal RNA (LSU rRNA) gene of the green alga Chlamydomonas eugametos. In each clone of S. sclerotiorum examined, including several clones which were sampled over a 3-year period from geographically separated sites, all isolates either had the intron or lacked the intron within the mt SSU rRNA gene. Screening by means of Southern hybridization and PCR amplification detected the intron in the mt SSU rRNA genes of S. minor, S. trifoliorum and Sclerotium cepivorum, but not in other members of the Sclerotiniaceae, such as Botrytis anamorphs of Botryotinia spp., or in other ascomycetous and basidiomycetous fungi. PMID- 7788721 TI - In vitro self-splicing reactions of chloroplast and mitochondrial group-I introns in Chlamydomonas eugametos and Chlamydomonas moewusii. AB - The self-splicing activity of nine chloroplast group-I introns (CeLSU.1 to CeLSU.6, CepsbC.1, CepsbC.2 and CmpsaB.1) and of one mitochondrial group-I intron (CmmtLSU.1) from the interfertile green algae Chlamydomonas eugametos and C. moewusii was examined using RNA templates produced by in vitro transcription of cloned DNA sequences. All introns, with the exception of the mobile intron CeLSU.5 encoding the site-specific I-CeuI endonuclease, were found to catalyze their own splicing in the absence of proteins. The introns that proved to be the best substrates under the conditions employed are CeLSU.1, CeLSU.3, CeLSU.4, CepsbC.1 and CmmtLSU.1. The implications of our results for the origin and spread of group-I introns in the organellar genomes of green algae are discussed. PMID- 7788722 TI - The rps3-rpl16-nad3-rps12 gene cluster in rice mitochondrial DNA is transcribed from alternative promoters. AB - The two gene clusters rps3-rpl16 and nad3-rps12 are separated from each other in the mitochondrial genome and are expressed as the individual transcription units in many plants. In rice mitochondrial DNA (mtDNA), the four genes rps3, rpl16, nad3 and rps12 are located within a region of 6 kbp. Northern-blot analysis revealed that a large transcript (6.6 kb) hybridized to both the rps3-rpl16 and the nad3-rps12 gene clusters. Using RT-PCR, we amplified a fragment of anticipated size (790 bp) from two primers that corresponded to sequences in the coding regions of rpl16 and nad3, demonstrating that at least two of the four genes, namely rpl16 and nad3, were co-transcribed. These results together indicated that all four genes, namely, rps3, rpl16, nad3 and rps12, were co transcribed in rice mitochondria. Transcription initiation sites were determined by an in vitro capping/ribonuclease protection assay and primer extension analysis. Two initiation sites were identified in the rps3-rpl16-nad3-rps12 gene cluster: one was located upstream of rps3 and the other was located between rpl16 and nad3. This evidence indicates that the rps3-rpl16-nad3-rps12 gene cluster is transcribed from two alternative promoters. PMID- 7788725 TI - [Serum amyloid protein A--a new kind of apoproteins Apo SAA]. PMID- 7788726 TI - [Progress in the molecular pathology of the clonal origin of hepatocellular carcinoma]. PMID- 7788723 TI - Calmodulin-dependent protein kinase II and calmodulin are required for induced thermotolerance in Saccharomyces cerevisiae. AB - We show here that yeast mutants lacking calmodulin-dependent protein kinase II fail to fully acquire induced thermotolerance. A similar result was also obtained with mutants depending solely on either the N-terminal half or the C-terminal half of calmodulin. These findings indicate that both calmodulin-dependent protein kinase II and calmodulin are required for induced thermotolerance. PMID- 7788727 TI - [A comparison between astrocytoma cells and the developing astrocytes in human embryo brain by electron microscopy]. AB - 60 cases of astrocytoma of brain and 8 human embryo brains were studied with light and electron microscopy. The 5 types of tumor cells in astrocytoma include the undifferentiated, pre-astrocyte, astrocyte gemistocyte and tumor giant cells. Some similarities were found between the ultrastructure of astrocytoma and that of the developing astrocyte, the tumor cells somewhat resembling the cells of developing astrocytes. But certain differences were observed, the tumor cells were usually polymorphic with increased chromatin in nucleus, and asynchronism between nucleus and cytoplasm differentiation was sometimes found. The current nomenclature and classification of astrocytoma were evaluated and discussed, the author's opinion on classification was presented. PMID- 7788724 TI - The mcm2-1 mutation of yeast causes DNA damage with a RAD9 requirement for repair. AB - The minichromosome maintenance mutation, mcm2-1, has been found to synthesize damaged DNA at 35 degrees C. Growth at this temperature rendered the mutant strain more sensitive to killing by ultraviolet irradiation. DNA damage could also be detected by pulsed-field gel electrophoresis, where a higher fraction of the DNA loaded was retained in the inserts at the wells. During the exponential phase of growth at this temperature about 50% of the cells had large buds, with the nucleus at or near the neck of the bud in most cases. The incorporation of the rad9 deletion in the mcm2-1-carrying strain caused a reduction in the percentage of large-budded cells and a moderate loss of cell viability. The results are consistent with mcm2-1 causing DNA damage leading to the arrest of cells in the S/G2 phase of the cell cycle, which was partially dependent on the RAD9 gene product. PMID- 7788728 TI - [Expression of Epstein-Barr virus encoded small RNA-1 and latent membrane protein 1 in midline T-cell lymphomas]. AB - Nine cases of midline T-cell lymphoma (MTL) were studied for expression of Epstein-Barr virus (EBV) encoded small RNA-1 (EBER-1) and EBV latent membrane protein-1 (LMP-1) using in situ hybridization and immunohistochemistry respectively. EBER-1 was detected in nuclei of tumor cells in 8/9 cases of MTL and LMP-1 was found on membrane and in cytoplasm of tumor cells in 7/9 cases of MTL. The results show: (1) There is a strong association between EBV and MTL. EBV may play an important role in the pathogenesis of MTL. (2) The detection frequency of EBV in MTL is higher than peripheral T-cell lymphoma from other sites of the body. (3) EBER-1 in situ hybridization and LMP-1 immunohistochemistry are sensitive and reliable in detection of EBV in MTL and the latter is more economic and convenient. PMID- 7788729 TI - [Malignant rhabdoid tumor of kidney: a clinicopathologic and immunohistochemical study of 15 patients]. AB - The clinical and pathological features of 15 infants with malignant rhabdoid tumors of kidney are presented. These tumors were identified among 391 primary renal neoplasms in this hospital. The male/female ratio was 2.8:1.0, mean age at diagnosis was 18 months with a range from 4 to 55 months. Of the 10 patients with follow-up records, 8 have died, 2 were alive and free of disease 15 and 55 months after the diagnosis respectively. A wide histologic spectrum was encountered. All tumors exhibited classical morphology in at least some areas, characterized by solid proliferation of monotonous tumor cells with vesicular nuclei and prominent nucleoli, abundant cytoplasm and intracytoplasmic inclusions. Immunohistochemical studies were performed in all 15 cases. Vimentin was positive in all tumors, ENA in 12, cytokeratin in 8, desmin in 2 and myoglobin in one. All cases were negative for presence of lysozyme, NSE and neurofilament. Our results show that this tumor is a distinctive and highly malignant neoplasm of the infant kidney with considerable morphological and immunohistochemical diverse phenotypes. PMID- 7788730 TI - [Transferrin receptor and iron deposition pattern in the hepatic lobules of the iron-deficient and iron-overloaded rats]. AB - Wistar rats were made iron deficient by a low iron regimen. Iron overload was produced by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe(3+)-NTA) for one to four months. Hepatic tissues from these iron deficient, overloaded and control rats were examined for transferrin receptor (TfR), transferrin (Tf) and iron after immunohistochemical staining. TfR and Tf were mainly distributed in the peripheral part of the lobule (zone 1) in the normal, iron deficient and iron-overloaded rats. The staining intensity decreased from zone 1 to zone 3. The staining intensity of TfR was strongest in iron-deficiency rat hepatic cells, weakest in iron-overloaded rat hepatic cells when compared with controls. The difference of Tf staining between the three groups of rats was similar to that of TfR. In the iron-overloaded rats, the staining intensity of iron was stronger in zone 1 than in zone 2 and 3, similar to the distribution pattern of TfR and Tf. These findings suggest that (1) iron uptake in hepatic cells in vivo is regulated and mediated by TfR and Tf, (2) the expression pattern of TfR and Tf in zone 1 to zone 3 liver cells may result in the progressive decrease of iron deposition in the hepatic lobules of the iron overloaded rats. PMID- 7788731 TI - [Detection of the apoptosis-suppressing oncoprotein bcl-2 in ameloblastomas]. AB - The product of apoptosis-suppressing oncoprotein bcl-2 can block apoptosis and result in the development of tumors. In this study, the expression of bcl-2 was observed in 40 cases of ameloblastomas by immunohistochemical staining. The results showed that the epithelium and reduced enamel epithelium of the enamel organ, the odontoblasts, basal cells of odontogenic cysts, normal oral epithelium and 90% (36/40) of ameloblastomas were positive for bcl-2, indicating that the expression of bcl-2 in odontogenic epithelium may be related to the degree of differentiation and proliferation of cells, the overexpression of bcl-2 may be associated with the development of ameloblastoma. PMID- 7788732 TI - [Congenital pulmonary lymphangiectasis]. AB - Six rare cases of congenital pulmonary lymphangiectasis were presented. The macroscopic characteristic of the lungs was honeycomb appearance due to extreme dilatation of the lymphatic spaces in the subpleural, interlobular, peribronchial and perivascular connective tissue. They had thin walls lined by endothelium. The dilated lymphatics may be due to congenital developmental defects or obstruction of major lymphatics, but they appeared to be associated only with pulmonary venous hypertension. PMID- 7788733 TI - [Tuberculous lymphadenitis: a sarcoidosis-like variation]. AB - By means of polymerase chain reaction technique to amplify DNA sequence specific for mycobacterium tuberculosis (M. TB-PCR), BCG immunohistochemistry (BCG-IHC) as well as acid fast stain (AF), mycobacterium other than tuberculosis (MOTT) and mycobacterium tuberculosis (M. TB) were detected in paraffin blocks from 12 cases diagnosed by consultant pathologists as lymph node "sarcoidosis". Of the 5 cases which consulting pathologists unanimously agreed to the lymph node "sarcoidosis" diagnosis, 1 case showed BCG-IHC (+) and M. TB-PCR (+); Of the 7 cases which most of the consulting pathologists agreed to be "sarcoidosis", 1 case showed AF (+), BCG-IHC (+) and M. TB-PCR (+). The results suggest: (1) some tuberculous lymphadenitis cases may present as "sarcoidosis"-like lesions; (2) lymph node sarcoidosis may be related to MOTT and M. TB infection. PMID- 7788734 TI - [The relationship of intraacinar pulmonary arterial structural remodelling with pulmonary hypertension]. AB - Pulmonary hypertension (PHT) was induced in rats by a single subcutaneous injection of monocrotaline (MCT). Light and electron microscopy, immunohistochemistry and morphometry were applied to investigate the different pathological changes of the intraacinar pulmonary arteries (IAPA) and their relationship with PHT. The results showed that pulmonary function was related to the morphological structure and indicated that the remodelling in the IAPA structure was the pathological basis of PHT. The results further suggested that the proliferation and myoid differentiation of the pericyte play an important role in the muscularization of the nonmuscular pulmonary artery in IAPA. PMID- 7788735 TI - [Expression of c-erbB-2 protein and EGF receptor in hepatitis B, cirrhosis and hepatocellular carcinoma]. AB - The expressions of c-erbB-2 oncogene and epidermal growth factor receptor (EGFR) were investigated immunohistochemically in specimens from 184 cases of hepatitis B, cirrhosis and hepatocellular carcinoma (HCC) and 29 normal liver specimens. EGFR was expressed in 36% (48/134) of the hepatocellular carcinoma and chronic liver disorder specimens and it was immunolocalized mainly in the sinusoidal endothelial cells. No significant difference was found between EGFR expression in HCC and in benign chronic liver disorders. These results indicate that EGFR may have some role in the proliferation of the sinusoidal epithelial cells in chronic liver disease. Low level c-erbB-2 expression was observed in 5/29 (17%) of normal liver specimens. In chronic hepatitis B and liver cirrhosis, its expression was found in all specimens. c-erbB-2 protein was immunolocalized mainly in small polygonal liver cells (SPLCs) and hepatocytes in small-cell dysplasia (SCD) and in ductular metaplasia (DM); c-erbB-2 expression in HCC cells was found to be weaker than in SPLCs, the hepatocytes in SCD and in DM. These results indicate that activated c-erbB-2 oncogene may have a role in human HCC genesis through promoting the development of SCD from SPLC proliferation and the progression of SCD. The close relation between the expression of c-erbB-2 and HBxAg imply that the activation of c-erbB-2 in human liver tissues may be related to HBV X gene. PMID- 7788737 TI - [Analysis of the quality of special charts]. PMID- 7788736 TI - [Implementing the theories of management to evaluate nursing quality]. PMID- 7788739 TI - [Psychological care for psychogenic patients]. PMID- 7788738 TI - [Care of arteriovenous fistula constructed with titanium ring nails]. PMID- 7788740 TI - [Care of drilling skull drainage for intracranial hematoma]. PMID- 7788742 TI - [Functional rehabilitation of burns of the neck]. PMID- 7788741 TI - [Care of ovarian cancer treated with intraperitoneal chemotherapy]. PMID- 7788744 TI - [Study on the influence of patients' posture on hemodynamics]. PMID- 7788745 TI - [Pre- and post-nursing care of endoscopic retrograde cholangiopancreatography in children]. PMID- 7788743 TI - [Life events and personal emotional reaction correlated to psychosomatic health]. PMID- 7788746 TI - [Retrospective analysis of the examination record of the field range of the eye]. PMID- 7788747 TI - [The influence of students' reports on "My viewpoint of children" on pediatric nursing teachers]. PMID- 7788748 TI - [Setting up nursing process course for technical nursing education]. PMID- 7788750 TI - [How long to keep the urinary catheter after abdominal gynecological surgery]. PMID- 7788749 TI - [Management of rehabilitation in Japan]. PMID- 7788751 TI - [Study on disposable infusion equipment]. PMID- 7788752 TI - [The function of OPD clients' nurse guide]. PMID- 7788753 TI - [Role assignment and continuing education for college graduate nurses]. PMID- 7788754 TI - [How to cultivate students' interest in basic nursing teaching]. PMID- 7788755 TI - [Diarrhea and pseudomembranous enteritis after major abdominal surgery]. PMID- 7788756 TI - [Clinical study on Huo Xue San Je Gao in treating scleroma caused by intramuscular injections]. PMID- 7788757 TI - [Study on childrens' health ideas in the Shanghai area]. PMID- 7788758 TI - [The after effect of r-HuEPO in treating anemic hemodialysis patients]. PMID- 7788759 TI - [Cognition behavior therapy of anorexia nervosa]. PMID- 7788760 TI - [Care of epidemic hemorrhagic fever complicated by bradycardia]. PMID- 7788761 TI - [Care of broncho-biliary fistula caused by hydatidosis]. PMID- 7788762 TI - [Care of entercutaneous fistula]. PMID- 7788763 TI - [How to protect the intravenous chemotherapy blood vessels]. PMID- 7788764 TI - [Visual acuity test of children in the strabismus clinic]. PMID- 7788766 TI - [Care of eye patients during ERG examination]. PMID- 7788765 TI - [Study on early eyedrops after cataract surgery]. PMID- 7788767 TI - [Comprehensive evaluation of nursing with weighted composite index number methods]. PMID- 7788768 TI - [Analysis of anthropometry of hospitalized medical patients]. PMID- 7788769 TI - [The clinical significance of taking body temperature for burn patients by mouth, axilla and rectum]. PMID- 7788770 TI - [Study of the influence of axillary temperature by the length of time of the thermometer in the axilla]. PMID- 7788771 TI - [Study on the need of nurses on the job for continuing education to renew their knowledge]. PMID- 7788772 TI - [Care of body surface malignant tumors with electrochemotherapy]. PMID- 7788773 TI - [Care of acute myocardial infarction complicated with cardiac rupture]. PMID- 7788775 TI - [Analysis and comparison of different methods in topical treatment of herpes zoster]. PMID- 7788776 TI - [Care of dental implant during operation]. PMID- 7788774 TI - [Respiratory exercise for chronic respiratory system diseases of senile patients]. PMID- 7788777 TI - [Style of management and personal quality of managers]. PMID- 7788778 TI - [The extra degree courses open in Sichuan Province]. PMID- 7788780 TI - [Continuing education of nursing ethics for nurses on the job]. PMID- 7788779 TI - [Experience in classroom teaching]. PMID- 7788781 TI - [Review of nursing articles from military hospitals at command level appearing in the Chinese Nursing Journal]. PMID- 7788782 TI - [Study on the rational composition of intravenous penicillin compound solutions]. PMID- 7788784 TI - [Study on the effect of using moistened oxygen to treat chronic obstructive lung diseases]. PMID- 7788783 TI - [Study on close insulin wet compresses in treating bedsores]. PMID- 7788785 TI - [Clinical observation and care of repair of gastroschisis using autologous umbilical cord]. PMID- 7788786 TI - [Care of phimosis treated with balloon dilatation]. PMID- 7788787 TI - [Coordination during osseo-integrated implant surgery]. PMID- 7788788 TI - [Defects of primary nursing records and measures for control]. PMID- 7788789 TI - [Study on construction of secluded treatment rooms]. PMID- 7788790 TI - [Teaching new concepts of modern nursing theory to technical nursing students]. PMID- 7788791 TI - [Teaching plan of nursing practice in a psychiatric hospital]. PMID- 7788792 TI - [Treating skin infections of neonates with Xin-Qing lotions]. PMID- 7788793 TI - Determining one or more change points. AB - A statistical method is presented for determining whether a line has one or more change points at unknown locations. A change point is a point where a line suddenly changes its slope but is continuous, i.e. it does not jump. Change points are also referred to as break points or join points. A step-wise procedure is suggested which starts by fitting a straight line without points. Next a line with a single change point is fit to the data, and a statistical test is used to determine if the line with a single change point provides a significantly better fit to the data than the line with no change points. This can then be followed by fitting a line with two change points, etc. The problem of determining the number of change points that best fits the data is discussed. A modified version of Akaike's information criterion (AIC) is used to select the best number of change points to avoid over fitting. An example of fluorescence anisotropy measurements of the total phospholipid from the liver of a marine fish as a function of temperature is presented. PMID- 7788794 TI - Ganglioside GD1a generates domains of high curvature in phosphatidylethanolamine liposomes as determined by solid state 31P-NMR spectroscopy. AB - We have studied the effects of gangliosides on the polymorphic behaviour of phosphatidylethanolamines. The ganglioside GD1a promotes the formation of phases which give rise to isotropic 31P-NMR resonance lines, particularly in the temperature range of the L alpha to HII transition. In addition, higher mol fractions of ganglioside raise the L alpha to HII phase transition temperature. Our results demonstrate that small mol fractions of gangliosides can have profound effects on the molecular organization of phosphatidylethanolamines. PMID- 7788795 TI - Cholesteryl hemisuccinate-cholesterol interaction: miscibility properties of the sterols. AB - Miscibility of cholesterol and cholesteryl hemisuccinate was investigated by differential scanning calorimetry and small-angle X-ray scattering. In an excess of cholesterol, above 2:1 mol ratio, phase separation takes place into a mixed phase and an almost pure cholesterol phase. PMID- 7788796 TI - Exclusion of SP-C, but not SP-B, by gel phase palmitoyl lipids. AB - The interactions of the hydrophobic pulmonary surfactant proteins, SP-C and SP-B, with lipid bilayers were assessed by fluorescence energy transfer. SP-C and SP-B were labeled with the fluorescent probe, succinimidyl nitrobenzoxadiazolyl amino hexanoate (NBD). Fluorescence energy transfer from NBD-SP-C and NBD-SP-B to four distinct indocarbocyanine probes (CnDiI) was utilized to determine the association of the surfactant proteins with various lipid acyl chains. In lipid mixtures including DPPC and DPPG, SP-C was associated with shorter chain and unsaturated lipids below the bulk lipid phase transition. Longer chain saturated CnDiI were excluded from SP-C aggregates. In contrast, SP-B demonstrated little acyl chain preference. The association of SP-C with shorter chain and unsaturated lipids below the bulk phase transition is interpreted to arise from a mismatch in the length of the hydrophobic region of the SP-C alpha-helix relative to the length of the hydrophobic region of dipalmitoyl lipids in the gel phase. PMID- 7788798 TI - Photo-effect in phospholipid liposome containing riboflavin. AB - The photovoltage developed in a photoelectrochemical cell consisting of riboflavin (RFN), a neutral dye and phospholipid (PL) liposome in aqueous solution has been found to correlate with the Stern-Volmer constant (KSV) or quenching-rate constant (Kq) of RFN-PL studied by fluorescence spectra. A possible mechanisms of photovoltage generation suggests the photo-induced electron transfer from PL to RFN in liposome through the excited state molecular interaction. PMID- 7788797 TI - Phase behaviour of novel phospholipid analogues. AB - The phase behaviour of phospholipid analogues containing a phosphoramide moiety was investigated using polarized light microscopy. A complex liquid-crystalline polymorphism consisting of lamellar, and normal topology hexagonal and intermediate phases was observed and found to depend on the structure of the phosphoramide headgroup and its methylation. In addition, a lower consolute phase boundary in the micellar solution part of the phase diagram was observed in some systems. The aggregation behaviour of these novel amphiphiles was compared with that of quaternary ammonium and oligo-ethylene oxide amphiphiles. PMID- 7788799 TI - Microdomain formation in phosphatidylethanolamine bilayers detected by 2H-NMR. AB - In deuterium NMR spectra of phosphatidylethanolamine bilayers with an extremely high content of saturated fatty acids, each C1 deuteron of the glycerol backbone gave rise to a doublet [Yoshikawa et al., (1988) Biochim. Biophys. Acta 944, 321 328]. This suggests the presence of two backbone conformations, the exchange between which is slow on an NMR time-scale. The origin of the two conformations has been investigated in this work using saturated 1,2-diacyl-sn-glycero-3 phosphoethanolamine specifically deuterated in the glycerol backbone. The results showed that the two conformations originate from different domains, which have different fatty acid compositions. The differential scanning calorimetry of the bilayers suggested that the size of the domain is not large enough to show an independent phase transition. Thus, the formation of microdomains in the phosphatidylethanolamine bilayers has been concluded. Conformational difference in different domains was shown to be restricted to the C1 position of the glycerol backbone. The microdomains of phosphatidylethanolamine were retained even in the presence of other phospholipids. PMID- 7788800 TI - Monolayer study of mixtures of diacetylenic phosphatidylcholine and phospholipids containing metal-chelating iminodiacetic acid headgroup. AB - The mixing behavior of polymerizable diacetylenic phosphatidylcholine (1) with two diacetylenic phospholipids containing the iminodiacetic acid (IDA) functionality in the headgroup region was studied at the air-water interface. All three phospholipids contained tricosa-10,12-diynoyl acyl chains. In phospholipid 2, the choline group (-CH2-CH2-NMe3) was replaced by an -CH2-CH2-N-(CH2-COOH)2 functionality. In phospholipid 3, the IDA unit was linked to the phosphate headgroup via a sulfonate linker, -CH2-CH2-OS(O2)-O-CH2-CH2-. Monolayers were prepared by mixing polymerizable 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3 phosphocholine (1) with metal-chelating IDA phospholipids (2, 3) on a 10 mM CuCl2 subphase. Studies of monolayer properties of mixtures of 2 and 3 with 1 demonstrated that mixtures of 2 with 1 had better mixing behavior than mixtures of phospholipids 1 and 3. PMID- 7788801 TI - Kinetics and thermodynamics of emulsion delivery of lipophilic antioxidants to cells in culture. AB - Oil-in-water emulsions are being used increasingly for the delivery of lipophilic drugs, but the fundamental physicochemical principles governing such delivery have not been explored. We determined the kinetics and thermodynamics of delivery from emulsions to cells in culture for two lipophilic compounds, U74006 and U74500. Two fundamental properties dominate the delivery, (a) the concentration of the compound in the lipid phase of the emulsion is directly proportional to the concentration of the compound in cells at equilibrium, and (b) the rate of transfer is directly proportional to the concentration of particles in contact with the cells. Thus, the transfer is consistent with direct partitioning from the lipid phase of the emulsion to cells and occurs by the direct collision of emulsion particles with cells. The details of the mechanism of delivery differ between the two compounds. Specifically, delivery of U74006 is first-order with respect to the drug accumulating in the cells. The transfer of U74500 is best described as a sum of two simultaneous pseudo first-order processes consistent with delivery from a single donor compartment to two receiver compartments. Furthermore, two molecules of U74500 appear to be involved in each transfer event. Our results show that relatively simple principles govern the delivery of compounds from oil-in-water emulsions to cells. PMID- 7788802 TI - Sterol carrier protein-2 stimulates intermembrane sterol transfer by direct membrane interaction. AB - It is unclear how the cytosolic sterol carrier protein-2 (SCP-2) binds sterols and enhances sterol transfer between membranes. Therefore, human recombinant SCP 2 was used in conjunction with phase fluorometry, dialysis, and chemical labeling techniques to show if a direct membrane effect accounted for this activity. SCP-2 directly interacted with L-cell fibroblast plasma membrane vesicles as determined by increased fluorescence anisotropy of coumarin-labeled protein (CPM-SCP-2). Furthermore, a new fluorescence lifetime component due to plasma membrane-bound CPM-SCP-2 was observed. Dialysis studies with 3H- cholesterol loaded plasma membranes indicated that SCP-2, added to the donor compartment, stimulated sterol transfer whether or not the dialysis membrane was permeable to SCP-2. Nevertheless, ligand-binding experiments indicated that chemically blocking the SCP-2 sterol binding site inhibited the ability of SCP-2 to enhance sterol transfer between plasma membrane vesicles. SCP-2 did not stimulate plasma membrane fusion. Addition of SCP-2 to plasma membranes increased the anisotropy plasma membrane proteins covalently reacted with CPM, but not that of lipids labeled with the fatty acid analogue octadecyl rhodamine B. In conclusion, the data are consistent with SCP-2 stimulating intermembrane sterol transfer by direct interaction with sterol in the membrane and enhancing its desorption from the membrane. PMID- 7788803 TI - Phase behavior of mixtures of cholesterol and saturated phosphatidylglycerols. AB - The interaction of cholesterol with a series of saturated phosphatidylglycerols was investigated using differential scanning calorimetry and X-ray diffraction. We find that the miscibility of cholesterol in phosphatidylglycerol bilayers is lower than in the corresponding phosphatidylcholine bilayers and decreases with increasing acyl chain length of the phospholipid. The influence of the negative charge of the phosphatidylglycerol on cholesterol miscibility is discussed. PMID- 7788804 TI - Sphincter preserving techniques in rectal cancer and their limitations. AB - For a patient with a tumour in the anal canal or with the inferior margin 5 cm or less from the anal verge an abdominoperineal rectal excision with permanent sigmoid colostomy is the only available treatment. The Turnbull-Cutait pull through technique involved full mobilization of the rectum, complete eversion of the anorectal stump and pull-through of the colon, the excess of which was resected in the second stage of the operation, followed by suture of the colonic and rectal mucosa. Abdomino sacral resection has been practised by a few surgeons only. Abdominotransanal resection with sutured colo-anal sleeve anastomosis was the operation developed by Sir Alan Parks. In this operation the anorectal stump is not everted through the anus as in the Turnbull-Cutait operation. There has been a great revival of interest in low anterior resections with the introduction of the EEA instrument for stapling the colorectal anastomosis and there is still today a great enthusiasm for this technique. In an attempt to improve the results trial are going on at present to evaluate the importance of a J-configured neo rectum constructed from the sigmoid or descending colon and stapled to the top of the anal canal or handsutured to the pectinate line after endoanal mucosectomy. Many patients with rectal carcinoma are old and often suffer from intercurrent diseases such as hypertension, diabetes etc. There is considerable postoperative complication. An abdominoperineal resection with a colostomy is by no means outdated for an ultralow or low sited rectal cancer. PMID- 7788805 TI - [Conservative surgery in rectal cancer]. AB - The Authors analyse their experience about 387 cases operated for rectal cancer. The choice of the operation was not related to tumour's features, but was related to the location of the neoplasia. The safety margin of rectal resection was reduced up to a minimum of 2 cm. in lower tumours, where it was not possible to meet this condition an abdomino-perineal resection was performed. A lumbo-aortic lymphadenectomy with high ligature of inferior mesenteric artery was always performed; in 17 cases it was extended to the pelvic nodes. In all the patients the whole mesorectum was removed and a wide pelvic dissection was performed to avoid the so called cone effect. Since 1991 all the B2-C patients undergo preoperative radiotherapy. Recurrence rate and survival are similar both after abdomino-perineal and sphincter-saving resections. Among the different risk factors, the Authors have found a statistically significant relation only with the stage. The Authors, therefore, conclude that sphincter-saving resection is the best surgical procedure because of the god quality of life. They stress the importance of a lumboarotic lymphadenectomy with high ligature of inferior mesenteric artery. As far as the complementary therapy is concerned, the discussion is still open, especially about the timing and the choice of the adjuvant treatment. PMID- 7788806 TI - The leaking colorectal anastomosis; why does it happen and how do we prevent it? AB - The ingredients predisposing for an anastomotic leak can be attributed both to the patient and to the surgeon. Some causative elements can be remedied; others cannot be changed very much. In cancer surgery the quest for cure involves ligation of the inferior mesenteric artery in the treatment of left-sided tumours. This obviously creates a conflict with the goal of constructing a well circulated anastomosis. In the treatment of rectal cancers total mesorectal excision has in recent years been put forward as the crucial step in avoiding local recurrences. The use of drains is a matter of controversy. The rationale for using them is to avoid pelvic collections with subsequent infection. The anastomosis is the point of least resistance so this is where a pelvic abscess is liable to break through, thus creating a leak. The choice of anastomosis, single layer or double layer, has been extensively dealt with and is beyond the scope of this presentation. My opinion is that you should stick to the type of anastomosis you are familiar with and try to refine your technique as much as possible. Continuous surgical audit and improved surgical training are likely the most important measures to lower the complication rates in colorectal surgery. PMID- 7788807 TI - Colorectal cancer emergencies. AB - From the variety of operative choices for colorectal cancer emergencies, it is difficult to select the best one for the individual patient, who is often old and frail. Appropriate handling of the emergency situation is essential. Treatment of the patient's malignant disease is secondary. The choice of surgical procedure in colorectal cancer emergencies must be based on sound clinical judgement and should be in keeping with the technical skill and experience of the individual surgeon. Surgical failures have major negative consequences not only for the immediate postoperative course, but also for long-term survival and quality of life of these patients. PMID- 7788808 TI - [Local excision of rectal tumors: Y. Mason's operation]. AB - Twenty-nine patients with cancer of the low rectum were treated by local excision performed by a transsphincteric approach (Mason's operation). Patient's selection requires a careful digital examination, biopsy, CT or MR and intraluminal ultrasound. In our series an accurate and strictly selection provides low recurrence rates with no mortality and low postoperative complications. Mason's operation, when criteria for appropriate patients selection are followed, is a valid alternative to mayor surgical procedures as APR. PMID- 7788809 TI - [Continence in low resections]. AB - Anorectal function is an important problem after low anterior resection procedure. This paper reports the results from 14 patients undergoing to low resection at Surgical Pathology Institute of the University of Verona. In 12 cases the restoration of the bowel continuity has been obtained by colon-anal anastomosis (Parks Operation) and in 3 cases by colo-rectal anastomosis at the anorectal ring level. The patients have been examined in the preoperative and in the postoperative period by clinical and manometric study. The results confirm that low resection does not involve faecal continence. PMID- 7788810 TI - [Malignant tumors of the small intestine. Clinical and therapeutic considerations on 23 observed cases]. AB - Small bowel tumours observed by the Authors at the IInd Surgical pathology of Pavia University between 1974 and 1992 were reviewed. There were found 23 cases; istopathologic findings, clinical presentation, diagnostic aspects and therapeutic options are discussed. The primary role of surgery in the treatment of these cancers is emphasized, but this can be curative only if diagnosis has been timely. PMID- 7788811 TI - [Current trends in the treatment of perforated colonic diverticulitis]. AB - The authors, after having examined the cases of complicated diverticulitis operated between 1985 and 1993, confirm that the surgical treatment for this particular pathology is strictly dependent on the local or general seriousness. In the light of this they consider an operation for resection and anastomosis 1st stage justifiable only in selected cases; colostomy and drainage in particularly serious cases, preferring Hartmann's method of operation for the 3rd and 4th stages of Chappuis and Chon. The results obtained agree in a satisfactory manner with the data in the literature. PMID- 7788812 TI - [Ogilvie syndrome: a case report]. AB - The Authors report a case of Ogilvie's syndrome observed directly. Remembering this disease is extremely rare, they review the pathogenic hypotheses and clinical picture, describing particularly therapeutic, conservative and surgical management. PMID- 7788813 TI - [Primary non-Hodgkin's lymphomas of the colon: apropos of a case with double localization]. AB - A case of non-Hodgkin's lymphoma involving the caecum and the rectum was resected. The disease occurs in 1-4% of gastrointestinal neoplasms and comprises 0.2-0.65% of colorectal tumours. The caecum is frequently involved while primary malignant lymphoma localized to the caecum and the rectum is more uncommon. The most representative histological types are histiocytic or lymphocytic tumours. The disease commonly presents as a painful abdominal mass and is associated with weight loss and diarrhoea. Barium enema and pancolonoscopy are sufficient for diagnosis, but echotomography and Tc scan are useful for staging. Surgery is the treatment of choice and overall 5-years survival is 30-40%. The role of adjuvant therapy has not yet been clearly defined, although data from some studies indicate increased survival in those patients given adjuvant therapy compared with patients treated with surgical resection alone. PMID- 7788814 TI - [Tumor markers in malignant anorectal pathology]. AB - The Authors note the limits and the more rational directions of using the several tumour markers that they utilized in the study of the neoplastic pathology of the anus-rectum. They particularly point out the benefit as "dynamic indices" of variation of the tumor mass during the neoplasm's progress and treatment. For these neoplasies any new marker offers advantages of diagnostic accuracy and a greater specificity more CEA. Nevertheless other markers used appear interesting as biochemical parameters for tumour growth. The study and the tumour marker's development supported, in recent years, the introduction of new diagnostic methods that include the utilization of monoclonal localization of the tumour mass. PMID- 7788815 TI - [Dysplasia and colorectal neoplasms in a group of patients with ulcerative rectocolitis (URC)]. AB - In our Medical Department we examined 74 patients with ulcerative colitis between January 1987 and December 1992. All the patients have been controlled by colonoscopy and multiple rectal byopsies. As started by different studies, the ulcerative colitis is predictive of mucosal dysplasia alterations and colo-rectal carcinoma. Our experience confirms that the occurrence is not so high as reported by some preliminary studies. These results could probably attributed to better diagnostic and therapeutic strategies now available. PMID- 7788817 TI - [General international bibliography: colorectal carcinoma (1994)]. PMID- 7788816 TI - [Nuclear DNA in neoplastic pathology of the thyroid gland]. AB - We have analysed the nuclear DNA content in a series of 33 thyroid tumours (18 carcinomas and 15 adenomas) and, for comparison, in 189 nodular strumas and 17 tissue samples of normal thyroids, calculating cell cycle parameters and presence of aneuploid DNA. Cell suspensions were prepared for each of three tissue fragments taken for different areas of the surgical specimens. Cell subpopulations with aneuploid DNA content were present in 39% of carcinomas, 27% of adenomas, 20% of strumas, but were absent in the samples from normal thyroids. The presence of hyperdiploid DNA was much more frequent than that of hypodiploid DNA in all pathologic tissues. The mean proliferation index was 14.1 in the carcinomas, 6.6 in the adenomas, 7.1 in the strumas and 6.1 in normal thyroid tissues. The percent of histograms with a coefficient of variation of the G0-G1 peak greater than 5 was highest in the carcinomas (26%). The significance and implications of the reported data are discussed for the interpretation of thyroid neoplastic pathologies. PMID- 7788818 TI - Early diagnosis of colorectal cancer. AB - It is reasonable to suggest that survival in colorectal cancer is closely linked to the anatomical stage of the tumour, implying that detection and removal of less advanced cancers will lead to a prolongation of survival. Early diagnosis of colorectal cancer therefore should be an important goal to strive for. An effort to achieve early diagnosis may be based on identification of high risk patients, and screening of groups at intermediate risk of developing colorectal cancer. Patients with well defined precancerous conditions should be included in surveillance programme. Prophylactic surgical treatment should be considered in longstanding ulcerative colitis and familial polyposis syndrome. Improved methods of genetic mapping and identification of the genetic defects that predisposed to cancer will probably be of great importance in the future. To reach groups of the population for early diagnosis of colorectal cancer large-scale screening is probably necessary. A change towards less advanced cancers is likely to be the result of mass screening. Improved survival with acceptable cost-benefit ratio remains to be shown. PMID- 7788819 TI - [Reedition of the first Bulletin of the Society of Medical Sciences]. PMID- 7788820 TI - Are antiemetics cost-effective for children? PMID- 7788821 TI - The Virtual Anesthesiology Training Simulation System. PMID- 7788822 TI - Nitrous oxide does not increase vomiting in children after myringotomy. AB - The aim of this study was to establish whether nitrous oxide has a clinically important effect on postoperative vomiting in children after myringotomy. We studied 320 healthy children of ages 0.5-13 yr undergoing elective myringotomy and tube insertion. Induction and maintenance of anaesthesia were randomized to inhalation with either 70% N2O/30% O2/halothane or 100%O2/halothane. Surgical technique and postoperative management were not influenced by this study. Vomiting in the recovery room (PAR) and Day Care Surgical Unit (DCSU) was recorded by nurses unaware of the anaesthetic technique. Parents were contacted 24-48 hr after surgery to ascertain the incidence of vomiting after discharge. The groups were similar with respect to demographic data, except that the anaesthesia time was greater among the 158 patients in the N2O-treated group (11 +/- 4 vs 12 +/- 4 min, mean +/- SD). The incidence of vomiting was 13% in both groups. Most of the 42 patients that had emesis only vomited once or twice. The incidence of vomiting was not altered by sex (13% vs 13%) or duration of anaesthesia. The incidence of vomiting increased with increasing age. The children aged less than 3 yr vomited 4% of the time, those aged 3-5 vomited 11% of the time, those aged 6-8 yr vomited 17% of the time, while the incidence of vomiting among those aged 9-13 yr was 31%. Vomiting prolonged the postoperative hospital stay from 75 to 92 min, P < 0.001, ANOVA. In summary, we have been unable to demonstrate that N2O induces vomiting by children after a brief general anaesthetic for myringotomy. PMID- 7788823 TI - Oral ondansetron decreases vomiting after tonsillectomy in children. AB - Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our double-blind, placebo-controlled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2-14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg.kg-1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N2O. Vecuronium 0.1 mg.kg-1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N2O, 50 micrograms.kg-1 midazolam iv and 1-1.5 mg.kg-1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of in-hospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg.kg-1 dimenhydrinate iv for vomiting x 2 and 50 micrograms.kg-1 droperidol iv for vomiting x 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic in hospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children. PMID- 7788824 TI - Incidence of malignant hyperthermia reactions in 2,214 patients undergoing muscle biopsy. AB - To determine the incidence of malignant hyperthermia (MH) reactions after trigger free anaesthesia in a large population of MH-susceptible (MHS) patients, the charts of 2,214 patients who underwent elective muscle biopsy for malignant hyperthermia were reviewed. Either general or regional anaesthesia with non triggering drugs was used. For general anaesthesia, the trachea was intubated in the absence of muscle relaxants. The halothane/caffeine contracture test was performed on the biopsied muscle. Suspected MH reactions were identified according to their site of occurrence (in the operating room, recovery room or ward). Ninety-seven percent of patients received a general anaesthetic; 3% received a regional anaesthetic or field block. Of the 2214 patients whose muscles were biopsied, 1082 patients were biopsy-positive for MH. Five patients in whom MH reactions were diagnosed in the recovery room were all subsequently proved to be biopsy-positive for MH. Four of the five received intravenous dantrolene as part of their therapy; the fifth received only symptomatic therapy as parenteral dantrolene was not commercially available. All patients recovered completely from their reactions. We conclude that the incidence of MH reactions in biopsy-positive patients who receive a trigger-free anaesthetic for minor surgery is small (0.46%, (0.15-1.07%, 95% CI)). These reactions occur in the immediate postoperative period. PMID- 7788825 TI - Self-administered intranasal meperidine for postoperative pain management. AB - Recent studies have demonstrated that intranasal is comparable to intravenous opioid titration in its pain-relieving effect. In these studies, however, the intranasal opioid titration was performed by the investigator, and the treatment period was two hours or less. The purpose of this randomized, prospective study was to investigate whether intranasal opioid administration by the patients themselves for a prolonged postoperative period may be regarded as a therapeutic alternative for postoperative pain management. Forty-four orthopaedic patients were studied over a 12-hr period on the first day after surgery. Twenty-two had free access to intranasal meperidine (nasal group) and were allowed to administer six intranasal puffs (27 mg per dose). The next self-administration was only permitted after a delay of at least ten minutes. Another 22 patients received intermittent subcutaneous meperidine injections (25 or 50 mg) on request (sc group). Pain intensity was recorded at 30-min intervals with the aid of the 101 point numerical rating scale. The pain score was lower in the nasal than in the sc group at the 30, 150 to 330, 420 to 480 and 540 to 600 min measuring points (P = < 0.05). The meperidine requirement was 112.9 +/- 81.3 mg in the nasal and 103.4 +/- 41.5 mg in the sc group (NS). Two patients in each group complained of nausea and vomiting. Thirteen of the 21 nasal and nine of the 15 sc patients who completed the final questionnaire rated the pain management as excellent or good (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788826 TI - Thoracic epidural clonidine and morphine for postoperative pain relief. AB - This study was undertaken to evaluate the potentiation of the postoperative analgesic effect of thoracic epidural morphine by coadministration of thoracic epidural clonidine in a randomized double-blinded design. Twenty patients underwent radical gastrectomy under combined general anaesthesia (enflurane and nitrous oxide/oxygen) and epidural anaesthesia with local anaesthetics. They received a thoracic epidural bolus injection of either 0.05 mg.kg-1 morphine plus 3 micrograms.kg-1 clonidine (M+C group; n = 10) or 0.05 mg.kg-1 morphine alone (M group; n = 10) immediately before completion of surgery. All patients received iv morphine via patient-controlled analgesia (PCA) equipment for 24 hr postoperative period, and the PCA iv consumption of morphine was the primary variable of efficacy of the analgesic regimen. In addition, data analyses included mean arterial blood pressure, heart rate, respiratory rate, arterial blood gas measurement, sedation score, and visual analogue pain scale score (VAS). The cumulative number of iv morphine injections via PCA was less in the M+C group than in the M group at each hour for 24 hr postoperative period (P < 0.05), while the numbers of PCA morphine injections per hour beyond nine hours after surgery were higher in the M group than in the M+C group (P < 0.05). Sedation score was higher, and VAS and mean blood pressure were lower in the M+C group only at one hour after surgery compared with the M group. We conclude that the combined single thoracic epidural administration of morphine plus clonidine produces a more potent and longer lasting analgesia than does morphine alone. PMID- 7788827 TI - Modification of the haemodynamic responses to induction of anaesthesia and tracheal intubation with alfentanil, esmolol and their combination. AB - The purpose of this double-blind randomized work was to study the effect of alfentanil and esmolol and their half-dose combination on the increases of heart rate and arterial pressure and on the prolongation of the QTc interval of the ECG occurring during anaesthetic induction. Sixty ASA class I-II patient with mean age ranging from 26 to 32 yr among the groups. Patients were allocated to one of four equal groups to receive saline, esmolol 2 mg.kg-1, alfentanil 0.03 mg.kg-1 and alfentanil 0.015 mg.kg-1+esmolol 1 mg.kg-1. Anaesthesia was induced with thiopentone. Succinylcholine was used to facilitate tracheal intubation. Haemodynamic variables were measured non-invasively and the QTc interval with the aid of a microcomputer. Comparisons between the groups were performed using two way analysis of variance with repeated measures. Both alfentanil and alfentanil esmolol prevented the increase of heart rate and arterial pressure caused by intubation whereas esmolol prevented only the increase of the heart rate. None of the treatments prevented prolongation of the QTc interval after intubation and only alfentanil prevented that after succinylcholine. The present results suggest that in the prevention of the haemodynamic responses to tracheal intubation, the half-dose combination of alfentanil and esmolol is as effective as alfentanil and superior to esmolol. The combination is preferable to relatively large doses of either drug in circumstances where side effects, such as respiratory depression due to alfentanil or bradycardia due to both drugs should be minimized. PMID- 7788829 TI - Maternal death following epidural anaesthesia for caesarean section delivery in a patient with unsuspected sepsis. AB - Sepsis in the parturient may be difficult to recognize in light of the physiological changes associated with pregnancy. The purposes of this report are to highlight the signs and symptoms which indicate an underlying septic process and the management of these patients in the peripartum period. This 32-yr-old GII PI woman with twin gestation presented at 36 wk in labour. Her temperature was 35.3 degrees C, she was normotensive and had a normal white blood cell count. After epidural anaesthesia was administered for Caesarean section, she became apnoeic, pulseless and unresponsive. Despite aggressive cardiopulmonary resuscitation, neither she nor her twin babies survived. Post mortem blood work revealed a considerable left shift of her white blood count (> 60% bands) and an anion gap acidosis. Autopsy revealed evidence of widespread Group A beta haemolytic streptococcal sepsis. Diagnosis of sepsis in the parturient involves assessment of the patient's temperature, WBC and differential and acid-base status. Evaluation of the intravascular volume must precede anaesthetic intervention. Epidural anaesthesia may be considered in the labouring and Caesarean section patient who has been fluid-resuscitated. Emergency operative delivery may result in cardiovascular compromise in the patient with severe sepsis. PMID- 7788830 TI - Alternating nitroglycerin and syntocinon to facilitate uterine exploration and removal of an adherent placenta. AB - Nitroglycerin (NTG) has been demonstrated to provide uterine relaxation in the management of various obstetric complications. A 32-yr-old woman presented 40 min postpartum for manual removal of a retained placenta. Repeated, alternating doses of NTG 250 micrograms and syntocinon (SYN) 10U iv were used over 15 min to produce periods of uterine relaxation and contraction respectively for uterine exploration. Multiple attempts to extract the placenta failed and a diagnosis of placenta accreta was made. There were no major side effects from this combination of drugs apart from a transient 20% decrease in blood pressure after NTG, which responded to ephedrine 10-15 mg iv. The rapid change in uterine tone was believed to be due not only to the short duration of action of NTG and SYN, but also to the possible physiological antagonism between the two drugs. The mechanism of interaction may involve calcium mobilization and myosin light chain phosphorylation. We conclude that NTG and SYN can be used to produce alternating periods of uterine relaxation and contraction rapidly and consistently with little sustained effects from either agents. PMID- 7788828 TI - Paediatric cardiac catheterization: innovations. AB - In recent years interventional procedures have been introduced to the field of paediatric cardiac catheterization. These procedures continue to develop in complexity and increasingly are being applied to patients with reduced cardiovascular reserve, as an alternative to cardiac surgery or when cardiac surgery with cardiopulmonary bypass is contraindicated. More frequently anaesthetists are being called upon to provide support in sedating, anaesthetizing or/and resuscitating these patients. The purpose of this review is to give a comprehensive update of the interventional procedures and to review the anaesthetic management techniques as they apply to the catheterization laboratory. We will discuss possible complications and management strategies from our own experience and the experience of others. We have observed that as more complicated procedures are performed the anaesthetist plays a pivotal role in the management of the patient from arrival to departure from the cardiac catheterization laboratory, and in preventing mortality and major morbidity. Although the economic consequences of interventional cardiological techniques remain unclear, the field continues to expand and more complex procedures are continually being introduced. PMID- 7788831 TI - Placental transfer of lidocaine hydrochloride after prolonged continuous maternal intravenous administration. AB - We treated a patient with arrhythmia during pregnancy with prolonged intravenous administration of lidocaine hydrochloride. This was a case of twin-to-twin transfusion syndrome and the arrhythmia was caused by ritodrine therapy. In total, 14.1 g lidocaine (50 mg.hr-1 for 282 hr) were used. Since there are no descriptions of human placental transfer of lidocaine after such a prolonged continuous intravenous administration, we measured lidocaine concentrations in maternal and fetal serum, and in the amniotic fluid (AF) at delivery. Fetal serum lidocaine concentrations (donor: 0.83 microgram.ml-1; recipient: 0.82 microgram.ml-1) were lower than in the maternal serum (1.6 micrograms.ml-1), while the AF lidocaine concentrations (donor: 1.05 micrograms.ml-1; recipient: 1.04 micrograms.ml-1) were higher than those of the fetal sera. The fetal/maternal concentration ratios of lidocaine were 0.52 for the donor and 0.51 for the recipient, which were similar to those described previously after administration of lidocaine in labour. PMID- 7788832 TI - Pressure support ventilation with the laryngeal mask airway: a method to manage severe reactive airway disease postoperatively. AB - The use of a laryngeal mask airway (LMA) and a bi-level positive airway pressure (BiPAP) machine is described in a post-operative thoracotomy patient with reactive airway disease. The LMA was placed to avoid reintubation of the trachea after a double lumen tube was no longer necessary. Placement in an awakening patient and positive-pressure ventilatory support were well tolerated and did not trigger a bronchospastic response. The patient was able to cough and breathe deeply with the LMA while receiving ventilatory assistance in the post anaesthesia care unit (PACU). The LMA is a therapeutic option to tracheal reintubation in patients who need postoperative ventilatory support after one lung anaesthesia. PMID- 7788833 TI - Upper airway involvement in Parkinson's disease resulting in postoperative respiratory failure. AB - A 71-yr-old man with a six-year history of Parkinson's disease (PD), Type II diabetes mellitus, myocardial infarction, and remote 20 pack-year smoking history, underwent an anterior resection of the rectum for carcinoma. Sixty hours later, the patient suffered a respiratory arrest; his antiparkinsonian medications had not been resumed. Preoperative flow-volume loops showed the characteristic saw-tooth pattern of PD indicating dysfunction of the striated muscle of the upper airway. Although postoperative respiratory distress was managed as lower airway obstruction, at the time of intubation there were no signs of lower airway pathology. Upper airway dysfunction and obstruction secondary to PD is thought to have been a contributing factor to the postoperative respiratory distress and failure. This case is presented to draw attention to the risk of upper airway dysfunction in Parkinson's Disease, especially with the withdrawal of antiparkinsonian medications. PMID- 7788835 TI - Donald A. Warren (1899-1971). PMID- 7788834 TI - Canadian anaesthesia physician resource planning--is it possible? AB - This study was undertaken with the objective of assessing current sources of information for anaesthesia Physician Resource Planning (PRP). Four major data bases, the annual reports of Health and Welfare Canada (H&W), the education statistics from the Canadian Post-M.D. Education Registry (CAPER), the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Physician Resource Data System of the Canadian Medical Association (PRDS), were examined for the period 1982 to 1991. The ratio of the number of surgical (S) to anaesthesia (A) clinicians decreased over this period despite an increase in the S:A ratios for trainees and certificants. The number of female anaesthetists has progressively increased. A steady decline in the number of rural anaesthetists has occurred. Age distribution of active certified anaesthetists revealed marked inter-regional differences. Little change was noted in the total mean hours worked per week. Each database provided valuable, but limited, data. The PRDS data is useful in assessing trends (age, sex and practice activity). Information provided by H&W tends to underestimate anaesthesia resource information by at least 10%. While information obtained from RCPSC and CAPER is accurate, the current mode of presentation of data limits their usefulness. Integrating data from all the databases appears to provide a meaningful assessment for PRP rather than assessing each database in isolation. Interpretation of the information and its value must take into account the limitations of the data being provided. Assessing present and planning future needs based on the current information structure will prove extremely difficult. PMID- 7788836 TI - Laryngeal mask airway for anaesthesia for cryopexy in low birth weight infants. PMID- 7788837 TI - Unusual regional block. PMID- 7788838 TI - Vasopressors and hypotension. PMID- 7788839 TI - Plasma cholinesterase deficiency in a neonate: a follow-up. PMID- 7788841 TI - DNA repair synthesis and DNA fragmentation in primary cultures of human and rat hepatocytes exposed to cyproterone acetate. AB - Cyproterone acetate (CPA), a synthetic steroid used in human therapy, has recently been shown to cause DNA damage in cultured rat hepatocytes and in rat liver. In the present study we have investigated whether CPA also induces genotoxic effects in human hepatocytes. Genotoxicity of CPA was determined by measuring the capability of the compound for inducing DNA repair synthesis and for causing the formation of DNA single-strand breaks. Autoradiography and alkaline elution were used to quantitate DNA repair and DNA fragmentation, respectively. Exposure of hepatocytes to CPA for 20 h induced DNA repair synthesis in two hepatocyte preparations derived from males and in four of the five preparations derived from females. In cultures from some donors, induction of repair was detected at 1 microM CPA, the lowest concentration tested. The maximum effect generally occurred at 10-20 microM. Only a very slight increase in the frequency of DNA single-strand breaks was found following exposure of the hepatocytes to 50 microM CPA for 20 h. For comparative purposes, the effects of CPA on DNA repair and DNA fragmentation were also determined in cultured rat hepatocytes. A strong induction of DNA repair synthesis, but only a slight enhancement in DNA fragmentation was observed in CPA-treated hepatocytes derived from female rats. These results indicate that the measurement of repair is a more sensitive indicator for the genotoxicity of CPA than the measurement of DNA fragmentation. No genotoxic effects of CPA were detectable in hepatocyte cultures derived from male rats. The present findings show that CPA is genotoxic in human hepatocytes and that the striking sex difference in the genotoxicity of CPA in rat cells is not observed with human cells. PMID- 7788840 TI - Role of GSTT1 and GSTM1 genotypes in determining individual sensitivity to sister chromatid exchange induction by diepoxybutane in cultured human lymphocytes. AB - The individual genotoxic response of cultured human lymphocytes to diepoxybutane (DEB), an epoxide metabolite of 1,3-butadiene, shows a bimodal distribution. Blood donors can be classified as either DEB-sensitive or DEB-resistant on the basis of the frequency of sister chromatid exchanges (SCEs) induced by DEB in whole-blood lymphocyte cultures. The genetic basis of this phenomenon has thusfar been unknown. To investigate if differences in the ability of individuals to detoxify DEB could explain the bimodal response, sister chromatid exchanges (SCEs) induced by a 48-h treatment with DEB (2 and 5 microM) were analyzed in whole-blood lymphocyte cultures of 20 human donors with known genotypes of two polymorphic glutathione S-transferases (GSTs), GSTT1 and GSTM1. Both polymorphisms include a homozygous null genotype lacking the respective GST gene and isozyme. The mean frequency of SCEs/cell was 1.6 times higher among GSTT1 null donors (n = 8) than GSTT1 positive donors (n = 12) at both 2 microM DEB (mean 67.3 versus 40.9) and 5 microM DEB (mean 123.2 versus 77.5), with no overlapping in DEB-induced individual SCE frequencies between the two genotypes. Thus, all DEB-sensitive individuals were of the GSTT1 null genotype, while all DEB-resistant persons had a detectable GSTT1 gene. A significant (P < 0.05) negative correlation (r = -0.65 at 5 microM, r = -0.56 at 2 microM) was obtained in the GSTT1 positive donors between DEB-induced individual SCE frequency and RBC GSTT1 activity, measured by formaldehyde formation from dichloromethane; the GSTT1 null individuals showed no GSTT1 activity. At 5 microM DEB, the lymphocyte cultures of the GSTT1 null donors also had a significantly decreased replication index, indicating an impact of GSTT1 genotype on the cytotoxicity of DEB. No influence on DEB-induced SCEs or cytotoxic effects was observed for GSTM1 genotype. It is concluded that sensitivity to in vitro SCE induction by DEB is explained by the lack of GSTT1. PMID- 7788842 TI - Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver. AB - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell division and cell death (apoptosis) in glutathione S-transferase (GST-P)-positive liver foci were analyzed in diethylnitrosamine-initiated female Wistar rats that were treated with TCDD, either acutely for 3 days or chronically for 115 days. Apoptotic bodies were quantitated in liver sections simultaneously stained for GST-P expression and H&E using a novel fluorescence microscopic detection method which greatly facilitates recognition of apoptotic bodies due to their high level of eosin fluorescence. While TCDD treatment only marginally affected cell division in GST-P-positive liver foci, as estimated by 5-bromo-2'-deoxyuridine labelling, apoptotic indices were decreased to approximately 60% and approximately 10% of control values after acute and chronic TCDD treatment, respectively. In normal liver tissue, apoptotic indices were only slightly reduced by TCDD treatment, suggesting selective inhibition of apoptosis in the enzyme-altered cell population by the dioxin. Since inhibition of apoptosis in GST-P-positive liver foci was by far more pronounced than changes in cell division, our data suggest that the promoting activity of TCDD is preferentially mediated by a decrease of apoptosis in enzyme-altered liver foci. PMID- 7788843 TI - Detection of O6-methylguanine, O4-methylthymine and O4-ethylthymine in human liver and peripheral blood leukocyte DNA. AB - O6-Methylguanine, O4-methylthymine and O4-ethylthymine were determined by a recently developed, highly sensitive and specific method (PREPI, pre fractionation, 32P-post-labeling and immunoprecipitation) in human liver DNA obtained from 15 autopsy specimens and in 15 peripheral blood leukocyte DNA samples obtained from healthy volunteers. All the cases had no obvious history of recent occupational or therapeutic exposure to alkylating agents. In the human liver DNA O6-methylguanine was detected in 13 cases at levels of 1.1-6.7 adducts/10(7) guanine; two cases were below the detection limit of approximately 1.1 x 10(-8). O4-Methylthymine and O4-ethylthymine were detected in all the liver samples at levels of 0.1-14 adducts and 0.5-140 adducts/10(7) thymine respectively. The mean value of the ratio of O6-methylguanine to O4-methylthymine was about 6. Among the three DNA adducts measured there was no significant correlation between any two combinations of adducts. In peripheral leukocytes of healthy volunteers O6-methylguanine was detected at 0.7-4.6 adducts/10(8) guanine, this being approximately 3-6% of that in livers. Neither O4 methylthymine nor O4-ethylthymine was above the detection limits. These results suggest that humans are exposed to exogenous and/or endogenous methylating and ethylating agents in daily life. PMID- 7788844 TI - Spectrum of mutations induced by methyl and ethyl methanesulfonate at the hprt locus of normal and tag expressing Chinese hamster fibroblasts. AB - This work describes the isolation and characterization of methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) induced 6-thioguanine-resistant mutants in normal and Escherichia coli tag gene expressing Chinese hamster fibroblast, RJKO, cells. It was previously shown that increased removal of 3-alkylated adenine, effected by 3-methyladenine DNA glycosylase I (Tag), reduces the frequencies of hprt mutations induced by alkylating agents which produce mostly N-alkylation (MMS and EMS) to half the normal rate. In order to identify which type of mutation is suppressed by increased 3-alkyladenine repair we have determined the DNA base sequence changes of the hprt cDNA in 61 independent MMS- and EMS-induced mutant clones. For both cell types and irrespective of the agent used, the majority of mutations were GC to AT transitions originating in the non transcribed strand. Only 6/55 base substitutions occurred at AT base pairs: five AT to GC transitions and one AT to CG transversion. Six mutations were found to be deletions. These results indicate that 3-alkylated adenines in DNA are not directly premutagenic. The fact that the mutation frequency is reduced by increased 3-alkyladenine removal might be explained by postulating the existence in mammalian cells of an SOS-like response turned on by cytotoxic lesions like 3 alkyladenine, or, alternatively, that increased removal of 3-alkyladenine increases the number of single-strand breaks in DNA, which stalls DNA replication and allows a prolonged time for DNA repair by the alkyltransferase. PMID- 7788845 TI - Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. AB - To elucidate what changes in the expression of gap junction proteins (connexins) occur at what stages during multistage mouse skin carcinogenesis in vivo, we immunohistochemically and morphometrically analyzed the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in papillomas, well-, moderately- and poorly differentiated squamous cell carcinomas, as well as in squamous cell carcinomas at invasion sites and those metastasized into lymph nodes in female CD-1 mice as a result of treatment with dimethylbenz[a]anthracene and 12-O tetradecanoylphorbol-13-acetate. In papillomas, no clear reduction of the two connexins was observed; however, Cx26 and Cx43 were frequently co-localized in the same gap junction plaques, whereas the two kinds of Cxs were differentially expressed in normal and surrounding non-tumorous epidermis. In squamous cell carcinomas, the expression of both Cx26 and Cx43 significantly decreased compared with surrounding non-tumorous epidermis and papillomas. The Western blot analysis confirmed that both Cx26 and Cx43 proteins were reduced in squamous cell carcinomas compared with papillomas. Furthermore, the expression of Cx26 was reduced as cancer cells became morphologically less differentiated, while that of Cx43 did not change. Squamous cell carcinomas at invasive sites showed clear reduction of Cx26 and Cx43. In squamous cell carcinomas metastasized into lymph nodes, Cx26 was expressed, but few carcinoma cells expressed Cx43. The localization of E-cadherin on the plasma membrane between cancer cells was maintained even at invasive and metastatic sites. Our data suggest that quantitative and qualitative changes in connexin expression are associated with tumor progression, including the loss of differentiation, and invasion and metastasis, during multistage mouse skin carcinogenesis. PMID- 7788846 TI - DNA damage as assessed by 32P-postlabelling in three rat strains exposed to dietary tamoxifen: the relationship between cell proliferation and liver tumour formation. AB - Tamoxifen was administered in the diet (420 p.p.m.) to female F344 (Fischer), Wistar (LAC-P) and LEW (Lewis) rats to determine for each strain the early morphological and biochemical changes associated with the subsequent development of liver cancer. Hepatic DNA damage, as determined by 32P-postlabelling, showed a cumulative increase with time from 500 adducts/10(8) nucleotides at 30 days to almost 3000 adducts/10(8) nucleotides after 180 days, with little difference between strains at this time point. A significant strain difference was found in the number of adducts present in the Fischer rats at 90 days, compared to the Wistar and Lewis strains. There was a marked strain differences in the time to development of liver tumours. After 6 months treatment, both Wistar and Lewis rats had tumours while none were seen in the Fischer animals. After 11 months, all of the Wistar and Lewis rats had developed liver carcinoma, while the Fischer rats developed liver carcinoma by 20 months. Depression in cell proliferation, relative to age-matched controls, was seen in the livers of Fischer rats after six months of exposure to tamoxifen, in contrast to an increase in the Wistar and Lewis rats. This observation is consistent with the promotion of foci to tumours and the subsequent progression of tumours to carcinomas in the latter two strains. These data may assist in establishing the possible risk factors, such as extent of DNA damage and increased liver cell proliferation, to women with long term prophylactic exposure to tamoxifen. PMID- 7788847 TI - Transplacental transfer of environmental genotoxins: polycyclic aromatic hydrocarbon-albumin in non-smoking women, and the effect of maternal GSTM1 genotype. AB - Transplacental transfer of genotoxic material has been determined by measuring the polycyclic aromatic hydrocarbon-albumin adduct level in serum isolated from the mother and the umbilical cord using a competitive ELISA assay and the antibody (8E11) against benzo[a]pyrene (B[a]P) tetrols. Smoking women (median 5.54 fmol B[a]P equiv/microgram albumin; 21 cases) and non-smoking women living in rural areas (median 4.99; 30) had higher adduct levels than non-smoking women living in suburbia (median 4.09; 37), whereas non-smoking women living in the city of Aarhus had an intermediate level (median 4.82; 40). Exposure to passive smoking did not modify the adduct levels. When all non-smoking cases were combined, the transport time to/from the home became a major contributing factor to the adduct level. The median adduct level in umbilical cord blood was significantly lower than in maternal blood, the maternal/fetal ratio being approximately 1.3, and a positive association between the adduct levels in the mother and umbilical cord blood was observed. The frequency of the GSTM1 null genotype in the study population, females aged 19-44, was 55.4%, but the GSTM1 genotype did not significantly alter the serum albumin adduct level. This study indicates that the competitive ELISA to detect B[a]P bound to serum albumin is sensitive enough to detect differences in the burden of genotoxic compounds in non-occupational exposed individuals. The lower adduct level in people living in suburbia suggests that local production of incomplete combustion products, like vehicle exhaust or heat generation, is the major contributing factor to genotoxic compounds in the general environment. PMID- 7788848 TI - Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol. AB - This study determined the incidence of prostate adenocarcinoma following long term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats. PMID- 7788849 TI - Rat CYP1B1: an adrenal cytochrome P450 that exhibits sex-dependent expression in livers and kidneys of TCDD-treated animals. AB - The broad spectrum of biological responses associated with exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is believed to be due to the alteration in expression of TCDD-inducible genes. The aim of this study was to investigate the effects of TCDD on the in vivo tissue-specific expression of the recently identified TCDD-inducible cytochrome P450 CYP1B1 [Sutter et al. (1994) J. Biol. Chem., 269, 13092-13099] in Sprague-Dawley rats. We cloned the 5.0 kb rat homolog of CYP1B1 from a TCDD-treated rat liver cDNA library and showed that the rat and human CYP1B1 predicted amino acid sequences are 80% identical. RNA hybridization analysis showed that CYP1B1 is constitutively expressed in the adrenal glands and also in the testes of untreated rats. This tissue distribution suggests that CYP1B1 may be a physiological steroid hydroxylase. Seventy-two hours post-administration of 25 micrograms/kg body wt TCDD by gavage, steady state levels of the 5.1 kb CYP1B1 RNA were increased > 50-fold in liver, and to a lesser extent in kidneys, lung, heart and ovaries. Average CYP1B1 RNA levels were significantly higher in the kidneys and livers of TCDD-treated females than in those from similarly treated males. In contrast, no significant sex-difference was observed in the levels of CYP1A1 in these tissues in TCDD-treated animals. In Sprague-Dawley rats, TCDD is a more potent hepatocarcinogen in females than in males. The induction of CYP1B1 in TCDD rat liver may be a contributing factor to the carcinogenic action of this persistent environmental pollutant. PMID- 7788850 TI - Effects of testosterone, testosterone propionate, 17 beta-trenbolone and progesterone on cell transformation and mutagenesis in Syrian hamster embryo cells. AB - Testosterone, testosterone propionate, 17 beta-trenbolone and progesterone, which represent the main endogenous and synthetic androgens and a progestin, were evaluated for possible cell transformation and genetic effects in Syrian hamster embryo (SHE) cells. Cell growth was reduced by treatment with the steroids at 10 30 micrograms/ml in a dose-related manner. Testosterone and testosterone propionate were less toxic than the other two steroids. Testosterone, testosterone propionate and progesterone induced morphological transformation of SHE cells with similar transformation frequencies. The most potent effects were observed with testosterone propionate, which induced cell transformation at 1-30 micrograms/ml in a dose-related manner. Testosterone and progesterone transformed cells only at the highest dose (30 micrograms/ml). 17 beta-Trenbolone did not induce a statistically significant level of cell transformations at any dose tested (up to 30 micrograms/ml). The transformation frequencies induced by testosterone, testosterone propionate and progesterone were less than one-half that induced by benzo[a]pyrene at 1 microgram/ml. None of these steroids induced significant increases in frequencies of chromosome aberrations or aneuploidy. Gene mutations were not observed for testosterone at the HPRT or Na+/K+ ATPase locus. Because these steroids are also associated with carcinogenic activity in vivo, these in vitro findings provide a model and new insights into the study of the mechanisms of androgen- and progestin-induced cell transformation. PMID- 7788851 TI - Cells transfected with transferrin receptor cDNA lacking the iron regulatory domain become more sensitive to the DNA-damaging action of oxidative stress. AB - Chinese hamster V79 cells were transfected with human transferrin receptor cDNA, lacking the 3' untranslatable regulatory sequence. One of the clones obtained was investigated completely. It exhibited the cDNA sequences recombined into the genome, transcribed the corresponding mRNA and became partially constitutive in iron uptake from transferrin. The rate of iron uptake was significantly higher in these cells than in the parental ones, as was the intracellular iron content, assessed indirectly by measuring the activation of the regulatory protein responsible for iron homeostasis control. The transfected cells were more sensitive to the DNA-damaging action of H2O2. This corroborates the important role that iron plays as a mediator of DNA damage by reactive oxygen species. It also points to the possibility that mutations at the regulatory sequences of transferrin receptors, leading to partial disturbance in iron homeostasis, might render the cells more prone to further mutations and malignant transformations by reactive oxygen species. PMID- 7788852 TI - Activation of phosphorylation of plasma membrane insulin-like growth factor-I receptors in the kidney of Syrian hamsters by diethylstilbestrol. AB - In the present work we have investigated activation of phosphorylation of plasma membrane insulin-like growth factor-I receptors (IGF-IR) by diethylstilbestrol (DES). Insulin-like growth factor-I (IGF-I) stimulated the activity of membrane protein tyrosine kinase(s) (PTK) in both normal and DES-treated hamster kidneys. The level of IGF-I-stimulated PTK(s) almost doubled after 15 days of DES treatment. Autophosphorylation experiments revealed that phosphorylation of a 95 kDa band (presumably the beta subunit of IGF-IR) was 2-fold higher in the membranes of kidney from DES-treated animals compared with controls. To understand the mechanism of activation of IGF-I-dependent PTK by DES, we investigated the relationship between the binding capacity of IGF-I to membrane proteins and the level of IGF-IR. The binding of [125I]IGF-I to membranes from the DES-treated group was 30% higher than that of age-matched normal kidney (P < 0.001). Scatchard analysis of the binding data for both normal and DES-treated hamster kidney revealed a single class binding site for IGF-I with a dissociation constant (Kd) of 4.1 and 4.6 nM and a maximum binding capacity (Bmax) of 1786 and 2086 fmol/200 micrograms protein respectively. Therefore, the difference observed in [125I]IGF-I binding between DES-treated and normal kidney membranes may be partially due to an increase in the number of IGF-I binding sites, with no change in the affinity of the receptors for IGF-I. An enhanced level of IGF-IRs in membranes from DES-treated animals was visualized by autoradiography following affinity labeling of membrane proteins subjected to SDS-PAGE. Under reducing conditions a molecular band of 132 kDa was evident. The 132 kDa band represents the alpha-subunit of IGF-IRs. Northern blot analyses revealed that DES treatment increased the level of IGF-IR mRNA 2-fold compared with that of controls. These findings suggest that an enhanced level of IGF-IR coupled with qualitative changes may be responsible for the activation of IGF-I-dependent PTK on DES exposure. Whether the stimulation of IGF-IR phosphorylation by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters is not clear. PMID- 7788853 TI - Promotion of N-nitrosodimethylamine-initiated mouse lung tumors following single or multiple low dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is highly toxic to several rodent species and may have adverse health effects in exposed human populations. Further, TCDD has been shown to be a potent liver tumor promoter in the rat after repeated administration. These studies were conducted to determine the tumor promoting capability of TCDD in the Swiss mouse following single or multiple exposures. Following tumor initiation with N nitrosodimethylamine (NDMA; 25 mg/kg), animals were given either a single dose (1.6, 16 or 48 micrograms/kg) or repeated injections (0.05 microgram/kg/week for 20 weeks) of TCDD and sacrificed at 52 weeks of age. Neither NDMA nor TCDD caused an increase in incidence of liver tumors. NDMA induced lung tumors in 100% of animals, with 12 +/- 0.1 tumors/mouse. The multiplicity of lung tumors was significantly increased by low dose TCDD treatment, with 20 +/- 2.6 tumors/mouse following a single 1.6 micrograms/kg dose (P = 0.016) and 18 +/- 1.7 (P = 0.031) following repeated 0.05 microgram/kg doses (x 20). Higher doses of TCDD did not increase multiplicity of lung tumors and, in fact, may have been toxic to the lungs of NDMA-treated mice, as evidenced by the infiltration of pigmented macrophages. These data demonstrate the potent tumor promoting capability of TCDD in mouse lung. PMID- 7788854 TI - Dose dependence of diethylnitrosamine-induced nuclear enlargement in embryonal turkey liver. AB - Avian embryos (turkey) were exposed to diethylnitrosamine in ovo. On the first day of incubation doses of 0.5-5.0 mg/egg were injected into the white of the fertilized egg. The experiment was terminated 4 days before hatching. Livers were removed and prepared for subsequent histological examination. In haematoxylin and eosin stained sections the areas of hepatocyte nuclear profiles were measured by semi-automatic image analysis. In liver samples of diethylnitrosamine-exposed embryos hepatocyte nuclei of more than twice the size of normal hepatocyte nuclei were found. The incidence of the enlarged nuclei was clearly dose dependent. An increase in the size of hepatocyte nuclei was observed after low doses of diethylnitrosamine that did not induce common signs of non-specific toxic effects, e.g. cell death, fat vacuoles or loss of glycogen. The slope of the dose response curve was rather steep. A 10-fold increase in the dose of the carcinogen resulted in a 100-fold increase in the incidence of enlarged hepatocyte nuclei. In combination with preneoplastic foci of altered hepatocytes, the quantification of nuclear enlargement can provide a valuable complementary parameter for the evaluation of carcinogen-induced effects in ovo. PMID- 7788855 TI - Mutagenicity and specific mutation spectrum induced by 8-methoxypsoralen plus a low dose of UVA in the hprt gene in diploid human fibroblasts. AB - Exposure of cells to 8-methoxypsoralen plus a low dosage of UVA (365 nm) generates mainly monoadducts (PUVA-I treatment), while further irradiation of PUVA-I treated cells after removal of 8-methoxypsoralen (PUVA-II treatment) converts a high frequency of monoadducts to crosslinks. In this study, a comparison was made of the cytotoxicity and mutagenicity of PUVA-I-treated cells obtained here with those induced by PUVA-II treatment in our previous report. PUVA-I treatment slightly affected the colony-forming ability of cells. However, the 6-thioguanine-resistant cells were markedly increased from 3/10(6) clonable cells in UVA-irradiated populations to 47/10(6) clonable cells in PUVA-I-treated populations. Those results indicated that PUVA-I was more mutagenic than PUVA-II at equal cytotoxic doses, implying that psoralen monoadducts are less cytotoxic and as mutagenic as crosslinks. Mutations in the hypoxanthine (guanine) phosphoribosyltransferase gene of independent PUVA-I mutants were characterized by direct sequencing of cDNA and/or genomic DNA that were amplified by polymerase chain reaction. All the 30 sequenced mutants had single base substitutions. Of those mutations, 21 occurred in the coding region and the others were in the consensus sequences at exon-intron boundaries, thereby resulting in aberrant cDNA. The majority of base substitutions were T to A transversions (23/30); 22 were located at the thymine of 5'TA sites. All of the 24 T.A base pair substitutions (including one T to C) had thymine located on the non-transcribed strand. Five of the six G.C base substitutions were located at the 5' TG or 5' CA sites on the non-transcribed strand. The frequencies of mutations at 5'TA and 5'TG/5'CA sites were similar in PUVA-I- and PUVA-II-induced mutants. However, the specific kind of T.A base pair substitutions induced by PUVA-I is strikingly different from that induced by PUVA-II. While the transient misalignment realignment model could account for PUVA-II-induced T.A base substitutions, the low cytotoxic effect and the specific T to A substitutions of PUVA-I treatment might be a result of rapid incorporation of nucleotides after insertion of an adenine or a thymine opposite the psoralen monoadducts on the template by DNA polymerases. PMID- 7788856 TI - Effect of three tumour promoters on the stability of hepatocyte cultures and apoptosis after transforming growth factor-beta 1. AB - Tumour promoters like the anti-androgen cyproterone acetate (CPA), the peroxisome proliferator nafenopin (NAF) and phenobarbital (PB) stimulate liver growth in rodents. Transforming growth factor-beta 1 (TGF-beta 1) is expressed in livers after treatment with CPA (Oberhammer et al., submitted) and some peroxisome proliferators. In this paper we describe the influence of CPA, NAF and PB on the stability of hepatocyte cultures and induction of apoptosis by TGF-beta 1. All three tumour promoters had a stabilizing effect on confluent monolayers of hepatocytes, partially preventing the usually occurring dedifferentiation and detachment processes. CPA on its own was able to induce apoptosis at the high dose of 10 microM. No induction of apoptosis could be observed after PB and NAF. At any dose above 0.01 microM CPA enhanced TGF-beta 1-induced apoptosis (5.8-fold increase with 10 microM CPA). Thus the combination of 10 microM CPA and 1 ng/ml TGF-beta 1 induced apoptosis in 90% of the plated hepatocytes. At a high dose (10 microM) NAF produced a 35% reduction in apoptosis induced by TGF-beta 1, in parallel with a stabilizing effect on cell number. PB did not affect the rate of apoptosis induced by TGF-beta 1. As demonstrated by immunohistochemical detection of PCNA, TGF-beta 1 prevented induction of PCNA by epidermal growth factor (EGF). No induction of PCNA was observable in CPA-treated cultures. In untreated and EGF treated cultures TGF-beta 1 was able to induce apoptosis to the same extent within 30 h. In CPA-treated cultures this period was shortened to 12 h. Thus CPA shortens the lag phase of induction of apoptosis by shifting hepatocytes to a point before S phase, where they are highly susceptible to TGF-beta 1-induced apoptosis. PMID- 7788857 TI - Anti-benzo[a]pyrene diolepoxide--DNA adduct levels in peripheral mononuclear cells from coke oven workers and the enhancing effect of smoking. AB - The level of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) bound to DNA of lymphocytes plus monocytes in 39 coke oven workers exposed to polycyclic aromatic hydrocarbons (PAH) and 39 non-exposed persons (controls) were investigated, each of the groups consisting of smokers and non smokers. The adduct level was measured by an improved HPLC/fluorescence method (Rojas, M., Alexandrov, K., van Schooten, F. J., Hillebrand, M., Kriek, E. and Bartsch, H., Carcinogenesis, 15, 557-560, 1994) through the release of the corresponding benzo[a]pyrene (B[a]P) tetrols. The anti-BPDE-DNA adduct was detected in 51% of coke oven workers exposed to PAH and in 18% of the non-exposed (control) subjects. The mean level of anti-BPDE-DNA adducts/10(8) nucleotides in coke oven workers (15.7 +/- 37.8) was approximately 8 times higher than in non exposed subjects (2.0 +/- 8.7). The interindividual variation of adduct levels was approximately 100-fold in coke oven workers and approximately 50-fold in controls respectively. Smokers in the exposed group had 3.5 times more DNA adducts than non-smokers. With the exception of one non-smoker with very high adduct levels (52.8 adducts/10(8)), the control subjects showed the presence of barely detectable adducts in only 16% of the samples examined. The increased in vivo formation in some smokers and high variability of anti-BPDE-DNA adducts in coke oven workers suggests variations in genetically controlled activation/inactivation reactions of PAH metabolism. PMID- 7788858 TI - Metabolism of the food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx) in nonhuman primates. AB - The metabolism and disposition of the food mutagen and rodent carcinogen 2-amino 3,8-dimethylimidazo[4,5-f]quinoxaline was investigated in cynomolgus monkeys. Monkeys were administered a single dose of radiolabeled [14C]MeIQx (2.2 or 50 mumol/kg). Peak blood levels of radioactivity were observed within 1-3 h after dosing and declined rapidly thereafter. By 72 h after dosing, approximately 50% and 70% of the 2.2 mumol/kg, and 50 mumol/kg dose, respectively, was excreted in the urine. Approximately 15-20% of either dose was recovered in the feces. Eight metabolites and the parent compound were detected in urine by HPLC. The parent compound accounted for approximately 15-25% of the dose excreted in the urine. Seven MeIQx urinary metabolites were identified. Five metabolites were identical to MeIQx metabolites previously found in rats: MeIQx-N2-glucuronide, MeIQx-N2 sulfamate, MeIQx-5-sulfate, MeIQx-5-O-glucuronide, and 8-CH2OH-MeIQx-5-sulfate. Cynomolgus monkeys, however, metabolized MeIQx to a novel glucuronide conjugate of MeIQx not found in rats. Based upon mass spectroscopy and proton NMR analyses, the structure of this metabolite was consistent with an N1-glucuronide of MeIQx. This metabolite was the major urinary metabolite found in monkeys, accounting for 31-37% of the dose excreted in the urine over a 24 h period. One additional metabolite identified in urine and feces of MeIQx treated cynomolgus monkeys, that has not been found previously in any other animal model, was 7-oxo-MeIQx, a likely enteric bacterial metabolite of MeIQx. 7-Oxo-MeIQx accounted for 20-25% of the dose of MeIQx found in the urine and was the major fecal metabolite. The N2 glucuronide conjugate of the carcinogenic metabolite 2-hydroxyamino-3,8 dimethylimidazo[4,5-f]quinoxaline (NHOH-MeIQx) was not detected in urine or bile of monkeys, even after 10 daily doses of MeIQx (100 mumol/kg) were given. The results indicate that MeIQx is metabolically processed in monkeys via multiple pathways of detoxification. However, MeIQx is poorly metabolically activated via cytochrome P450 mediated N-oxidation. The in vivo metabolism of MeIQx in cynomolgus monkeys is different from that of the structurally related food derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), which is readily metabolically activated by this species and in contrast to MeIQx, has been shown to be a powerful hepatic carcinogen. PMID- 7788859 TI - Localization of methylation sites in the human O6-methylguanine-DNA methyltransferase promoter: correlation with gene suppression. AB - Adducts of O6-alkylguanine in DNA that are induced by cytotoxic, carcinogenic or mutagenic alkylating agents can be removed by the DNA repair enzyme O6 methylguanine-DNA methyltransferase (MGMT). Human tumor cell lines that do not express this enzyme (Mer-) are hypersensitive to the effects of such alkylating agents, although the molecular basis of MGMT gene suppression is not yet understood. Previous studies suggested that Mer- cells deficient in this enzyme lack neither the gene nor the trans-acting factors necessary for normal transcription. Methylation of CpG dinucleotides is an attractive mechanism to account for suppression of the MGMT gene; however, there have been reports of both direct and inverse correlations between methylation and MGMT expression. We previously demonstrated an inverse correlation between methylation at a single SmaI site in the human MGMT promoter and gene expression. To substantiate this observation, we examined additional CpGs in the promoters of three Mer+ and three Mer- cell lines, using rare methylation-sensitive restriction sites, and then sought to identify the region where methylation correlated with gene expression. Six CpGs in the region from -245 bp to +225 bp (relative to the transcription start site) were completely unmethylated in all Mer+ cells, whereas in Mer- cells were at least partially methylated. The methylation status of CpGs further upstream did not correlate with MGMT expression. We conclude, therefore, that the association between CpG methylation and suppressed MGMT gene activity extends to sites other than SmaI but is limited to a core region of the promoter. PMID- 7788861 TI - Expression of Ah receptor (TCDD receptor) during human monocytic differentiation. AB - We have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals. In this paper, the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells. However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts. Furthermore, a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells. HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester, showing a 5- to 2-fold increase of AhR mRNA. The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7 fold increase of AhR mRNA. The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by these combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types. Treatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene. These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics. Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens. PMID- 7788860 TI - Expression of cytochrome P450 and microsomal epoxide hydrolase in cervical and oral epithelial cells immortalized by human papillomavirus type 16 E6/E7 genes. AB - Epidemiological evidence suggests that the presence of human papillomaviruses (HPV), when combined with smoking behaviors, considerably enhances the risk of developing oral, cervical, vulvar, and/or anal carcinomas. It is well established that the cytochrome P450 (CYP), microsomal epoxide hydrolase (mEH), and other biotransformation enzymes are important modulators of the bioactivation and detoxification of many environmental chemicals, including constituents of tobacco smoke such as certain nitrosamines and polycyclic aromatic hydrocarbons (PAH). Since there is little information regarding oral and cervical epithelial-specific expression of these genes, established primary and HPV-immortalized oral and cervical epithelial cell lines were analyzed for morphology, mRNA and protein expression patterns of specific CYPs and mEH. Primary human oral and cervical epithelial cells were immortalized using retroviral infection with HPV-16 E6/E7 genes. Primary human keratinocyte cells were immortalized by transfection of HPV 18 and made tumorigenic with nitrosomethylurea treatment. Expression profiles for mEH, CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP3A, and CYP2E1 were evaluated in these cultures in the presence or absence of a PAH inducer, using reverse transcriptase-coupled polymerase chain reaction analysis. mEH gene expression was evident in all cultures, while CYP2A6 mRNA was not detected in any of the cell lines, regardless of culture conditions. CYP2E1 mRNA expression was greatest in the oral epithelial cultures and detectable in all other epithelial cultures except for the HPV-18 immortalized keratinocyte cell line. Elevated levels of CYP2D6 mRNA existed in both oral epithelial cell lines and the HPV-16 immortalized cervical epithelial cells when compared to the other cell lines examined. CYP1A1 and CYP1A2 mRNAs were detected in all the cells and several cultures were inducible by PAH exposure. To corroborate the RT/PCR data, Western immunoblotting experiments were conducted on selected samples. Using these methods, CYP1A1 and CYP2E1 proteins were detected in primary and HPV-immortalized oral and cervical epithelial cultures. These data indicate that both primary and HPV immortalized cells appear to express certain biotransformation enzymes necessary for the activation of tobacco-specific nitrosamines and PAHs. Although the overall impact of HPV gene infection on expression of these systems remains to be fully elucidated, as in vitro system is characterized which should prove useful in examining interactive mechanisms of HPV with xenobiotic activation in the etiology of squamous cell carcinomas. PMID- 7788862 TI - Metabolism of aflatoxin B1 by rabbit and rat nasal mucosa microsomes and purified cytochrome P450, including isoforms 2A10 and 2A11. AB - The nasal mucosa of some mammalian species are susceptible to the toxicity of aflatoxin B1 (AFB1), a potent hepatocarcinogen, but little is known about the nasal enzymes involved in the metabolic activation of AFB1 or the metabolites produced. In the present study, the metabolism of AFB1 was studied with nasal microsomes from rats and rabbits and with several purified isozymes of rabbit P450 in a reconstituted enzyme system. The rates of AFB1-N7-guanine DNA adduct formation with rabbit and rat nasal microsomes are over 3- and 10-fold higher, respectively, than with liver microsomes from the same species. On the other hand, the rates of formation of AFM1 (9a-hydroxy-AFB1) and AFQ1 (3-hydroxy-AFB1) products known to be less toxic, are lower with nasal than with liver microsomes. Of particular interest, nasal microsomes produce high levels of six unidentified polar metabolites that are not formed by microsomes from liver or several other tissues. These same products are also generated by P450 NMa purified from rabbit nasal microsomes in a reconstituted system, but not by five other isozymes of cytochrome P450 (1A2, 2B4, 2E1, 2G1, 3A6) that are known to be present in nasal microsomes. AFB1-DNA adducts are formed by P450 NMa at a rate 3-fold higher than that by nasal microsomes. The DNA adducts are formed at much slower rates by P450s 2G1, 2B4, and 1A2, and adducts are not formed at measurable rates by P450s 2E1 and 3A6. Moreover, AFB1-DNA adduct formation is also catalyzed by cDNA derived, heterologously expressed P450s 2A10 and 2A11, both of which are known to be present in the purified P450 NMa preparation. The Km and Vmax values of the two isozymes for DNA adduct formation are comparable to those for nasal microsomes. Furthermore, the formation of AFB1-DNA adducts by nasal microsomes is decreased by nicotine, a known inhibitor of P450 NMa. These data indicate that members of the P450 2A gene subfamily play an important role in the metabolic activation of AFB1 in rabbit and rat nasal mucosa and suggest a molecular basis for assessing the health risk associated with inhalation exposure to this procarcinogen in humans. PMID- 7788863 TI - DNA adduct formation in B6C3F1 mice and Fischer-344 rats exposed to 1,2,3 trichloropropane. AB - 1,2,3-Trichloropropane (TCP) is a multispecies, multisite carcinogen which has been found to be an environmental contaminant. In this study, we have characterized and measured DNA adducts formed in vivo following exposure to TCP. [14C]TCP was administered to male B6C3F1 mice and Fischer-344 rats by gavage at doses used in the NTP carcinogenesis bioassay. Both target and nontarget organs were examined for the formation of DNA adducts. Adducts were hydrolyzed from DNA by neutral thermal or mild acid hydrolysis, isolated by HPLC, and detected and quantitated by measurement of radioactivity. The HPLC elution profile of radioactivity suggested that one major DNA adduct was formed. To characterize this adduct, larger yields were induced in rats by intraperitoneal administration of TCP (300 mg/kg). The DNA adduct was isolated by HPLC based on coelution with the radiolabeled adduct, and compared to previously identified adducts. The isolated adduct coeluted with S-[1-(hydroxymethyl)-2-(N7-guanyl) ethyl]glutathione, an adduct derived from the structurally related carcinogen 1,2 dibromo-3-chloropropane (DBCP). Analysis by electrospray mass spectrometry suggested that the TCP-induced adduct and the DBCP-derived adduct were identical. The 14C-labeled DNA adduct was distributed widely among the organs examined. Adduct levels varied depending on species, organ, and dose. In rat organs, adduct concentrations for the low dose ranged from 0.8 to 6.6 mumol per mol guanine and from 7.1 to 47.6 mumol per mol guanine for the high dose. In the mouse, adduct yields ranged from 0.32 to 28.1 mumol per mol guanine for the low dose and from 12.2 to 208.1 mumol per mol guanine for the high dose. The relationship between DNA adduct formation and organ-specific tumorigenesis was unclear. Although relatively high concentrations of DNA adducts were detected in target organs, several nontarget sites also contained high adduct levels. Our data suggest that factors in addition to adduct formation may be important in TCP-induced carcinogenesis. PMID- 7788864 TI - Site specific reduction of colon cancer incidence, without a concomitant reduction in cryptal cell proliferation, in 1,2-dimethylhydrazine treated rats by diets containing 10% pectin with 5% or 20% corn oil. AB - The effects of specific dietary interventions on incidence of carcinogen-induced cancer and on cryptal cell proliferation in areas of the colon located either over aggregates of lymphoid nodules (ALN) or away from ALN was investigated. Groups of dimethylhydrazine (DMH) treated rats or non-DMH-treated rats were fed a basal AIN-76 diet less fiber of any type, or the basal fiber free diet supplemented with 10% pectin and with 5%, 10%, or 20% corn oil. The adenocarcinoma (AC) incidence was determined in regions of the colon, i.e. ascending, descending, descending over the ALN and descending away from the ALN. The results indicate that: (i) factors associated with ALN promote AC formation, (ii) dietary modifications (addition of pectin and of 20% corn oil to the diet) each cause significant site specific suppression of AC incidence, (iii) DMH treatment rendered crypts non-responsive to the suppression of cryptal cell proliferation which occurred in the rats not treated with DMH (suggestive of a DMH-induced loss in the regulation of cell proliferation) and (iv) reduction of AC incidence was not always accompanied by reduction in crypt cell proliferation. Studies of intervention procedures designed to prevent colon cancer should take into account the colon site specific tumorigenic response to the preventive agent and should not rely on a single biomarker to predict the efficacy of the intervention. PMID- 7788865 TI - Mammary carcinogenicity in female CD rats of a diol epoxide metabolite of fluoranthene, a commonly occurring environmental pollutant. AB - We examined the mammary carcinogenicity in CD rats of anti-2,3-dihydroxy-1,10b epoxy-10b,1,2,3-tetrahydro-fluoranthene (FDE), a genotoxic metabolite of the environmental pollutant fluoranthene. FDE (2 mumol or 10 mumol) in 0.1 ml dimethyl sulfoxide (DMSO) was injected beneath each of the three left thoracic nipples of groups of 20 rats each, with 0.1 ml DMSO alone being injected under the right nipples. On the next day, the procedure was repeated for the three inguinal nipples on each side. anti-3,4-Dihydroxy-1,2-epoxy-1,2,3,4 tetrahydrobenzo[c]-phenanthrene (BcPDE, 2 mumol per nipple) was used as a positive control and DMSO alone as a negative control. Tumor development was assessed weekly by palpation and the experiment was terminated after 41 weeks. Eighty five percent of the rats in each of the FDE treated groups developed histologically confirmed mammary tumors, compared to 11% in the DMSO treated animals (P < 0.01). Most tumors were on the left side. The lower dose of FDE induced a significant number of adenomas while the higher dose induced significant incidences of both adenomas and adenocarcinomas compared to controls. BcPDE was a powerful mammary carcinogen, confirming our previous observation. The results of this study demonstrate the carcinogenicity of FDE to the CD rat mammary gland. Since FDE is a potentially transportable human metabolite of fluoranthene, its possible role as an etiologic factor in breast cancer deserves further study. PMID- 7788866 TI - Non-specific inhibition of cytochrome P450 activities by chlorophyllin in human and rat liver microsomes. AB - Chlorophyllin, a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, inhibits the mutagenicity of 2-amino-3-methylimidazo[4,5 f]quinoline (IQ), 3-amino-1-methyl-5H- pyrido[4,3-b]indole (Trp-P-2), aflatoxin B1 and benzo[a]pyrene (B[a]P). Recent in vitro and in vivo studies have shown that a molecular complex is formed between IQ and chlorophyllin, suggesting that this complex formation might be responsible for the antigenotoxic effect of chlorophyllin observed. Cytochrome P450 (P450) enzymes appear to be the major catalysts in the bioactivation of these carcinogens. We have investigated the in vitro effects of chlorophyllin on several P450 activities including ethoxyresorufin O-deethylation, benzyloxyresorufin O-debenzylation, coumarin 7 hydroxylation, 7-ethoxycourmarin O-deethylation, B[a]P 3-hydroxylation, and chlorzoxazone 6-hydroxylation. Chlorophyllin non-specifically inhibited all of P450 activities observed. Spectrally detectable P450 was also destroyed in microsomes and purified P450 in a reconstituted system in the presence of chlorophyllin and an NADPH-generating system. These results suggest that the antigenotoxic effect of chlorophyllin might be due to inhibition of P450 enzymes involving bioactivation of carcinogens in addition to molecular complex formation between carcinogens and chlorophyllin. Comparison of the apparent Ki for P450 inactivation with previously estimated constants for chlorophyllin-IQ complexation suggest that P450 inhibition should be the dominant mechanism of inhibition. PMID- 7788867 TI - Molecular regulation of atrioventricular valvuloseptal morphogenesis. AB - The majority of congenital heart defects arise from abnormal development of valvuloseptal tissue. The primordia of the valve leaflets and membranous septa of the heart are the cardiac cushions. Remodeling of the cushions is associated with a transitional extracellular matrix that includes sulfated proteoglycans and the microfibrillar proteins fibulin and fibrillin. Cushion formation is restricted to the AV canal and ventricular outflow tract regions of the primary heart tube. The proper placement of the cushions may be the result of the development of the primary heart tube as a segmented organ, as well as the subsequent looping of the heart. Segmentation of the heart tube may be demonstrated by the alternating molecular expression pattern along the longitudinal axis. In support of this hypothesis is the restricted expression of BMP-4 and msx-2 to the AV canal and ventricular outflow tract. The importance of looping for cushion positioning may imply that the iv and inv genes and retinoic acid are important for the proper patterning of the heart. The cells of the cushions evolve from endocardial cells that undergo an epithelial-to-mesenchymal transformation. This developmental event is regulated by the myocardium and is probably due to the production of protein complexes, present within the cardiac jelly of the cushion-forming regions, that consist of fibronectin and the ES proteins. Both the cushion mesenchyme and its endocardial cell antecedents express JB3, an ECM protein. JB3 expression is also featured within the heart-forming fields of the primary mesoderm, from which the endocardial progenitors of the cushion cells originate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788868 TI - Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. AB - A new cardiotonic agent, (R)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3 pyridazinyl)-phenyl] hydrazono]propanedinitrile (Levosimendan), has been developed and screened for its ability to bind to cardiac troponin C. In perfused hearts, low concentrations of 0.03 or 0.1 mumol/L Levosimendan increased +dP/dt, but did not affect the speed of relaxation and produced only a slight increase in spontaneous heart rate in the hearts perfused with 0.1 mumol/L of the drug. In these same hearts, perfusion with 0.03 mumol/L Levosimendan did not alter the 32P incorporation into troponin I or C protein, whereas a slight but significant increase was noted for phospholamban, with no detectable change in tissue cAMP levels. Administration of 0.1 or 0.3 mumol/L Levosimendan significantly increased myocardial cAMP levels as well as the phosphorylation of phospholamban, troponin I, and C protein. Levosimendan (0.03 to 10 mumol/L) reversibly increased force generated by detergent-extracted fiber bundles over a range of submaximally activating free Ca2+ concentrations with no significant effect on maximum force or on Ca2+ binding to myofilament troponin C. There was no direct effect of Levosimendan on Ca2+ uptake by vesicles of sarcoplasmic reticulum (SR). In contrast, under conditions optimal for cAMP-dependent phosphorylation, Levosimendan slightly but significantly lowered the concentration of Ca2+, yielding half-maximal uptake rates by the SR vesicles. Our results indicate that at low concentrations Levosimendan acts preferably as a Ca2+ sensitizer, whereas at higher concentrations its action as a phosphodiesterase inhibitor contributes to the positive inotropic effect. PMID- 7788869 TI - Alpha 1-adrenergic receptor stimulation decreases maximum shortening velocity of skinned single ventricular myocytes from rats. AB - alpha 1-Adrenergic agonists have negative inotropic effects on mammalian myocardium under some conditions, and biochemical experiments measuring the Ca(2+)-activated actomyosin ATPase activity of myofibrillar preparations suggest that this may result from a decrease in cross-bridge cycling rate caused by phosphorylation of myofilament proteins. Experiments with intact ventricular preparations, however, have failed to demonstrate a mechanical manifestation of a decrease in cycling rate. The present study examined the effect of alpha 1 adrenergic receptor stimulation on maximum shortening velocity in skinned single ventricular myocytes from rats. Enzymatically isolated myocytes were incubated with the beta-receptor antagonist propranolol in the presence or absence of the alpha 1-adrenergic receptor agonist phenylephrine and were then rapidly skinned to preserve the phosphorylation state of myofilament proteins. The velocity of unloaded shortening (Vo) was determined by use of the slack-test method and compared between skinned control and phenylephrine-treated cells. The relationship between isometric tension and [Ca2+] was also assessed for each myocyte. Vo was significantly lower in the alpha 1-adrenergic receptor agonist treated cells than in the control cells, but there was no effect on Ca2+ sensitivity of isometric tension. In addition, the myosin heavy chain isoform composition accounted for a significant amount of the variation in Vo within the treatment groups. On the basis of these and previous results we propose that alpha 1-adrenergic receptor stimulation inhibits cross-bridge cycling rate at the level of myofilament proteins by a mechanism that may involve phosphorylation of troponin I by protein kinase C. PMID- 7788870 TI - [Ca2+]i inhibition of K+ channels in canine renal artery. Novel mechanism for agonist-induced membrane depolarization. AB - The patch-clamp technique was used to examine the inhibition of delayed rectifier K+ channels by agents that release intracellular Ca2+. During voltage-clamp experiments on isolated myocytes with 4-aminopyridine (4-AP, 10 mmol/L) and niflumic acid (100 mumol/L) present to inhibit delayed rectifier K+ current (IK(dr)) and Ca(2+)-activated Cl- current (ICl(Ca)), angiotensin II (Ang II) and caffeine increased Ca(2+)-activated K+ current (IK(Ca)) between -25 and 80 mV (n = 5). Conversely, with charybdotoxin (ChTX, 100 nmol/L) and niflumic acid (100 mumol/L) present to inhibit IK(Ca) and ICl(Ca), Ang II and caffeine only caused inhibition of IK(dr). Block was achieved within 15 seconds of drug application and was reversible upon washout (n = 5). The effects of Ang II on IK(Ca) and IK(dr) were inhibited by the specific Ang II receptor antagonist losartan (1 mmol/L, n = 3). Intracellular BAPTA (10 mmol/L) also abolished the effects of Ang II and caffeine on both IK(Ca) and IK(dr). In current-clamp experiments, the application of ChTX (100 nmol/L) and niflumic acid (100 mumol/L) caused little change in resting membrane potential; however, subsequent application of caffeine (10 mmol/L) caused a 26 +/- 2.9 mV depolarization from -54 +/- 3.1 to -28 +/- 1.7 mV (n = 6). 4-AP (10 mmol/L) blocked the caffeine-induced depolarization. When isolated cells were loaded with the Ca2+ indicator indo 1 (100 mumol/L), Ang II, caffeine, and 4-AP increased [Ca2+]i and depolarized the cells. Both Ang II and caffeine caused an increase in [Ca2+]i that preceded membrane depolarization, whereas 4-AP depolarized the cell first and then caused an increase in [Ca2+]i (n = 4). In inside-out patches, with 200 nmol/L ChTX in the patch pipette to block large-conductance Ca(2+)-activated K+ channels, a 45 +/- 7-picosiemen 4-AP sensitive K+ channel was identified that was sensitive to cytoplasmic Ca2+ (n = 6). Increasing intracellular Ca2+ decreased channel opening probability [NxP(open), where N is the number of functional channels in a patch and P(open) is the opening probability] at all membrane potentials examined. At 0 mV, increasing Ca2+ from < 5 to 200 and 600 nmol/L free Ca2+ decreased NxP(open) by 52 +/- 3% and 73 +/- 7%, respectively (n = 6). The decrease in opening probability of the delayed rectifier K+ channel resulted from a concentration- and voltage-dependent decrease in mean open time. The decrease in mean open time reflected significant decreases and increases in open and closed time constants, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7788871 TI - [Ca2+]i inhibition of K+ channels in canine pulmonary artery. Novel mechanism for hypoxia-induced membrane depolarization. AB - Experiments were performed on smooth muscle cells isolated from canine pulmonary artery to identify the type of K+ channel modulated by hypoxia and examine the possible role of [Ca2+]i in hypoxic K+ channel inhibition. Whole-cell patch-clamp experiments revealed that hypoxia (induced by the O2 scavenger, sodium dithionite) reduced macroscopic K+ currents, an effect that could be prevented by strong intracellular buffering of [Ca2+]i. The inhibitory effects of hypoxia were mimicked by acute exposure of cells to caffeine and could be prevented by caffeine pretreatment, suggesting an important obligatory role of [Ca2+]i in hypoxic inhibition of K+ currents. Exposure of cells to low concentrations of 4 aminopyridine (4-AP, 1 mmol/L) prevented hypoxic inhibition of macroscopic K+ currents, whereas low concentrations of tetraethylammonium were without effect, suggesting that the target K+ channel inhibited by hypoxia is a voltage-dependent delayed rectifier K+ channel, which is inhibited by [Ca2+]i. Hypoxia failed to consistently modify the activity of large-conductance (118 picosiemens [pS] in physiological K+) Ca(2+)-activated K+ channels in inside-out membrane patches but reduced open probability of smaller-conductance (25-pS) delayed rectifier K+ channels in cell-attached membrane patches. In inside-out membrane patches, 1 mumol/L Ca2+ added to the cytoplasmic surface significantly reduced open probability of small-conductance (25-pS) 4-AP-sensitive delayed rectifier K+ channels. Whole-cell current measurements using symmetrical K+ to increase driving force for small currents active near the cell's resting membrane potential revealed the presence of a 4-AP-sensitive K+ current that activated near -65 mV and was inhibited by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788872 TI - Two components of the delayed rectifier K+ current in ventricular myocytes of the guinea pig type. Theoretical formulation and their role in repolarization. AB - Two distinct delayed rectifier K+ currents, IKr and IKs, were found recently in ventricular cells. We formulated these currents theoretically and investigated their roles in action potential repolarization and the restitution of action potential duration (APD). The Luo-Rudy (L-R) model of the ventricular action potential was used in the simulations. The single delayed rectifier K+ current in the model was replaced by IKr and IKs. Our results show that IKs is the major outward current during the plateau repolarization. A specific block of either IKr or IKs can effectively prolong APD to the same degree. Therefore, either channel provides a target for class III antiarrhythmic drugs. In the simulated guinea pig ventricular cell, complete block of IKr does not result in early afterdepolarizations (EADs). In contrast, > 80% block of IKs results in abnormal repolarization and EADs. This behavior reflects the high IKs-to-IKr density ratio (approximately 8:1) in this cell and can be reversed (ie, IKr block can cause EADs) by reducing the ratio of IKs to IKr. The computed APD restitution curve is consistent with the experimental behavior, displaying fast APD variation at short diastolic intervals (DIs) and downward shift at longer DIs with the decrease of basic drive cycle length (BCL). Examining the ionic currents and their underlying kinetic processes, we found that activation of both IKr and IKs is the primary determinant of the APD restitution at shorter DIs, with Ca2+ current through L type channels (ICa) playing a minor role. The rate of APD change depends on the relative densities of IKr and IKs; it increases when the IKr-to-IKs density ratio is large. The BCL-dependent shift of restitution at longer DIs is primarily attributed to long-lasting changes in [Ca2+]i. This in turn causes different degrees of Ca(2+)-dependent inactivation of ICa and different degrees of Ca(2+) dependent conductance of IKs at very long DIs (> 5 s) for different BCLs. This BCL dependence of ICa and IKs that is secondary to long-lasting changes in [Ca2+]i is responsible for APD changes at long DIs and can be viewed as a "memory property" of cardiac cells. PMID- 7788873 TI - Arrhythmia and delayed recovery of cardiac action potential during reperfusion after ischemia. Role of oxygen radical-induced no-reflow phenomenon. AB - The role of reactive metabolites of oxygen, oxygen radicals (O-Rs), as mediators of potentially arrhythmogenic alterations in cellular electrical properties and contractile dysfunction of cardiac muscle during reperfusion after ischemia was investigated. Electrical and mechanical activities of arterially perfused guinea pig right ventricular walls were recorded simultaneously with intracellular microelectrodes and a force transducer. Preparations were maintained in Krebs Henseleit solution (perfusion rate, 1.5 mL/min) and subjected to 30 minutes of no flow ischemia followed by 60 minutes of reperfusion or pretreated with O-R scavengers (superoxide dismutase, 50 U/mL; catalase, 600 U/mL; and mannitol, 2 mmol/L) for 10 to 20 minutes, followed by 30 minutes of ischemia and 60 minutes of reperfusion. Reperfusion in untreated preparations caused (1) depolarization of resting membrane potential by 8 to 10 mV and slow recovery of action potential duration requiring 60 minutes to attain the preischemic duration, (2) tachyarrhythmias and premature action potentials, (3) postischemic contractile dysfunction, and (4) increased coronary perfusion pressure in untreated preparations. Pretreatment with scavenger cocktail affected neither electrical nor contractile activity before or during no-flow ischemia, but it (1) accelerated recovery of resting membrane potential and action potential duration, (2) reduced the incidence of tachyarrhythmia, (3) improved contractile function, and (4) inhibited the rise in perfusion pressure on reflow. Reperfusion with an exogenous O-R-generating system containing xanthine/xanthine oxidase (X/XO, 2 mmol/L:10 mU/mL) inhibited recovery of action potential duration and contractility. Treatment of normoxic arterially perfused right ventricular walls with X/XO caused a decline in action potential duration by approximately 20% within 30 minutes. In contrast, X/XO caused a 30% increase in the duration of action potentials in superfused papillary muscles or small strips of right ventricular walls over the same time period. Pretreatment with sodium nitroprusside (10 mumol/L) inhibited the decline in duration induced by X/XO in normoxic right ventricular walls but was without effect on prolongation due to X/XO in papillary muscles. Reperfusion with nitroprusside after no-flow ischemia caused (1) accelerated recovery of preischemic action potential configuration, (2) a significant decline in the incidence of reperfusion arrhythmias, (3) improved postischemic contractile performance, and (4) inhibition of the increase in perfusion pressure associated with reflow. The data indicate that slow recovery of the action potential duration caused by O-Rs in reperfusion cannot be explained by the direct effects of O-Rs on cardiac myocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7788874 TI - Role of atrial contraction in diastolic pressure elevation induced by rapid pacing of hypertrophied canine ventricle. AB - The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6 +/- 3.1 mm Hg at baseline to 22.6 +/- 8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting. PMID- 7788875 TI - Dithionite increases radical formation and decreases vasoconstriction in the lung. Evidence that dithionite does not mimic alveolar hypoxia. AB - Dithionite is a powerful reducing agent used to deoxygenate hemoglobin and create anaerobic conditions in vitro. Recently, dithionite has been used as a convenient means of creating "hypoxia" in experiments studying the O2 sensor in the pulmonary circulation and carotid body. We evaluated the hypothesis that hypoxia created by hypoxic ventilation and that created by dithionite have different effects on the pulmonary circulation. In vitro, dithionite (10(-5) to 10(-3) mol/L), added to oxygenated Krebs' solution, rapidly created superoxide anion in a dose-dependent manner. Dithionite consumed O2 in parallel with the generation of superoxide radical, with both processes peaking within seconds. Anoxia was sustained only if resupply of O2 was prevented. In isolated rat lungs (whether perfused with autologous blood or Krebs' solution), hypoxic ventilation alone lowered perfusate PO2 from approximately 140 to 40 mm Hg and decreased lung levels of activated oxygen species (AOS), measured by luminol-enhanced chemiluminescence, before the onset of hypoxic pulmonary vasoconstriction. Constrictor responses to angiotensin II and KCl were not impaired by intermittent hypoxic challenges, and lung weight did not increase. In contrast, dithionite impaired constrictor responses of the Krebs' solution-perfused lungs to all vasoconstrictors tested and increased lung weight. When given as a bolus (5 x 10( 3) mol/L) into the pulmonary artery during normoxic ventilation, dithionite caused no vasoconstriction and only briefly lowered PO2 (because of constant resupply of O2 from the alveoli). When superimposed on hypoxic ventilation, dithionite further lowered PO2 from approximately 40 to approximately 0 mm Hg and caused additional constriction. Unlike hypoxic ventilation, dithionite increased AOS production. Antioxidant enzymes diminished dithionite-induced radical production and diminished the loss of vascular reactivity and lung edema. In conclusion, unlike hypoxic ventilation, dithionite causes edema and loss of vascular reactivity in the lung by generating superoxide anion and hydrogen peroxide. Hypoxia elicited by dithionite is not equivalent to authentic hypoxia because of the obligatory associated generation of AOS. Dithionite usage should not be substituted for authentic hypoxia in studies of O2 sensing. PMID- 7788876 TI - Transverse shear along myocardial cleavage planes provides a mechanism for normal systolic wall thickening. AB - Recent studies in humans and other species show that there is substantial transverse shear strain in the left ventricular myocardium, and others have shown transverse myocardial laminae separated by cleavage planes. We proposed that cellular rearrangement based on shearing along myocardial cleavage planes could account for > 50% of normal systolic wall thickening, since < 50% can be explained by increases in myocyte diameter. To test this hypothesis, we measured strains at two sites with different cleavage-plane anatomy in eight open-chest dogs. Columns of radiopaque markers were implanted in the left ventricular anterior free wall and septum. Markers were tracked with biplane cineradiography, and strains were quantified by using finite deformation techniques. Hearts were perfusion-fixed with glutaraldehyde, and cleavage-plane orientations at the bead sites were measured in three orthogonal planes. At subendocardial sites of the anterior left ventricular wall, where the cleavage planes approach the endocardium obliquely from the apical side of the surface normal in the longitudinal-radial plane (-67 +/- 11 degrees), systolic longitudinal-radial transverse shear (E23) was positive (0.14 +/- 0.08). At the septal sites where the subendocardial cleavage planes approach the endocardium obliquely from above the surface normal (44 +/- 12 degrees), E23 was negative (-0.12 +/- 0.08). The differences in cleavage-plane angle and E23 at the two sites were each highly significant (P < .0005). At both sites, the transverse shear strain accompanied substantial systolic wall thickening at the subendocardium (anterior, E33 = 0.44 +/- 0.16; septum, E33 = 0.22 +/- 0.14). These data are not representative of the behavior in midwall and outer wall sites, where cleavage-plane orientation was not consistently different between anterior left ventricle and septum. Our data indicate that rearrangement of myocytes by slippage along myocardial cleavage planes is in the correct direction and of sufficient magnitude in the subendocardium (inner third) to account for a substantial proportion (> 50%) of systolic wall thickening. Furthermore, three-dimensional reconstruction of the myocardial laminae and local comparison with maximum strain vectors indicate that for the inner third of the ventricular wall the maximum shear deformation is a result of relative sliding between myocardial laminae. PMID- 7788877 TI - Binding of A1 adenosine receptor ligand [3H]8-cyclopentyl-1,3-dipropylxanthine in coronary smooth muscle. AB - Vascular smooth muscle has been reported to contain the A1 subtype of adenosine receptors, but the existence of such receptor(s) in coronary smooth muscle has not been established. In the present study, the 3H-labeled A1-selective antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) was used to demonstrate the specific binding in porcine coronary artery smooth muscle membranes. The binding was saturable with a Bmax of 6.43 +/- 1.02 fmol/mg protein. Scatchard analysis of the binding data provided a single binding site with a Kd of 0.21 +/- 0.025 nmol/L. In the competition experiments, adenosine receptor agonists and antagonists showed the following order of potency (nmol/L): S-N6-(2-endonorbornyl)adenosine (S-ENBA) 0.11 = R(-)-N6-phenylisopropyladenosine 0.32 > DPCPX 3.2 = xanthine amine congener 2.4 = N6-cyclopentyladenosine 2.67 > 5'-(N-ethylcarboxamido)-adenosine 7.35 >> 2-[p-(2-carboxyethyl)-phenethyl-amino] 5'-(N-ethylcarboxamido)- adenosine 1000 > theophylline 83,000. This order of potency fits the criteria for the A1 adenosine receptor. S-ENBA, a highly selective A1 receptor agonist, was used to investigate the effect on isoproterenol-mediated vasorelaxation and cAMP accumulation. S-ENBA (0.1 to 10 nmol/L) dose-dependently shifted the isoproterenol-mediated (10(-8) to 10(-5) mol/L) vasorelaxation to the right in vascular rings. S-ENBA (10 nmol/L) inhibited the basal cAMP levels by 36% and attenuated the isoproterenol (10(-5) mol/L)-stimulated cAMP by 25% in the coronary rings. These inhibitory effects of S-ENBA on isoproterenol-mediated cAMP-accumulation and vasorelaxation were abolished by pertussis toxin (100 ng/mL, overnight) treatment of the arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788878 TI - Osmotic compression of single cardiac myocytes eliminates the reduction in Ca2+ sensitivity of tension at short sarcomere length. AB - According to the Frank-Starling relation, cardiac output varies as a function of end-diastolic volume of the ventricle. The cellular basis of the relation is thought to involve length-dependent variations in Ca2+ sensitivity of tension; ie, as sarcomere length is increased in cardiac muscle, Ca2+ sensitivity of tension also increases. One possible explanation for this effect is that the decrease in myocyte diameter as muscle length is increased reduces the lateral spacing between thick and thin filaments, thereby increasing the likelihood of cross-bridge interaction with actin. To examine this idea, we measured the effects of osmotic compression of single skinned cardiac myocytes on Ca2+ sensitivity of tension. Single myocytes from rat enzymatically digested ventricles were attached to a force transducer and piezoelectric translator, and tension-pCa relations were subsequently characterized at short sarcomere length (SL), at the same short SL in the presence of 2.5% dextran, and at long SL. The pCa (-log[Ca2+]) for half-maximal tension (ie, pCa50) increased from 5.54 +/- 0.09 to 5.65 +/- 0.10 (n = 7, mean +/- SD, P < .001) as SL was increased from approximately 1.85 to approximately 2.25 microns. Osmotic compression of myocytes at short length also increased Ca2+ sensitivity of tension, shifting tension-pCa relations to [Ca2+] levels similar to those observed at long length (pCa50, 5.68 +/- 0.11). These results support the idea that the length dependence of Ca2+ sensitivity of tension in cardiac muscle arises in large part from the changes in interfilament lattice spacing that accompany changes in SL. PMID- 7788880 TI - Acetylcholine-sensitive intracellular Ca2+ store in fresh endothelial cells and evidence for ryanodine receptors. AB - In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a transient release of Ca2+ from an intracellular store, presumably via an inositol tris-phosphate-sensitive mechanism. This ACh response could be repeated in the presence of extracellular Ca2+ but was obtained only once in Ca(2+)-free bathing solution, which shows that a depleted intracellular Ca2+ store can be rapidly refilled from the extracellular space. Refilling can be prevented by the endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 mumol/L), implying that Ca2+ enters the cytoplasm before accumulation in the endoplasmic reticulum. Ionomycin (10 mumol/L) caused a large Ca2+ release even after the ACh releasable store had been emptied, indicating the existence of other ACh insensitive stores, perhaps including the mitochondria. In one third of the cells studied, ACh induced oscillations in [Ca2+]i that were dependent on extracellular Ca2+. Also investigated were the effects of caffeine and ryanodine. In this cell preparation neither caffeine nor ryanodine induced a Ca2+ transient but instead slowly increased [Ca2+]i. It was observed that both caffeine and ryanodine were able to slowly deplete the ACh-sensitive store. These results indicate the presence of functional ryanodine receptors in native endothelial cells and demonstrate overlap between the caffeine and agonist-sensitive Ca2+ stores. We also found that caffeine was able to directly inhibit the process of ACh-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788879 TI - Functional identification of histamine H3-receptors in the human heart. AB - Norepinephrine release contributes to ischemic cardiac dysfunction and arrhythmias. Because activation of histamine H3-receptors inhibits norepinephrine release, we searched for the presence of H3-receptors directly in sympathetic nerve endings (cardiac synaptosomes) isolated from surgical specimens of human atria. Norepinephrine was released by depolarization with K+. The presence of H3 receptors was ascertained because the selective H3-receptor agonists (R) alpha methylhistamine and imetit reduced norepinephrine release, and the specific H3 receptor antagonist thioperamide blocked this effect. Norepinephrine release was exocytotic, since it was inhibited by the N-type Ca(2+)-channel blocker omega conotoxin and the protein kinase C inhibitor Ro31-8220. Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine. Also, thioperamide antagonized the effect of (R) alpha-methylhistamine. Our findings are the first demonstration that H3-receptors are present in sympathetic nerve endings in the human heart, where they modulate adrenergic responses by inhibiting norepinephrine release. Since myocardial ischemia causes intracardiac histamine release, H3-receptor-induced attenuation of sympathetic neurotransmission may be clinically relevant. PMID- 7788881 TI - Endothelial cell interactions with synthetic peptides from the carboxyl-terminal heparin-binding domains of fibronectin. AB - Fibronectin (FN) plays an important role in endothelial cell adhesion, spreading, and motility. Within FN, a number of functional domains have been identified, including the 33/66-kD carboxyl-terminal heparin-binding fragments, which support the adhesion of vascular endothelial cells. A number of synthetic peptides representing amino acid sequences within the 33/66-kD fragments have been shown to promote the adhesion, spreading, and migration of a variety of cell types. Our working hypothesis is that one or more of these sequences may also mediate vascular endothelial cell adhesion, spreading, and migration to the 33/66-kD fragments. In support of this hypothesis, we have demonstrated that endothelial cells from various sources adhered in a concentration-dependent manner to surfaces coated with FN, the 33/66-kD fragments, and synthetic peptides derived from the 33/66-kD fragments of FN. FN and the 33/66-kD fragments also promoted endothelial cell spreading and migration. Although each of the six synthetic peptides tested supported endothelial cell adhesion, only one of these peptides within the carboxyl-terminal heparin-binding domain (FN-C/H-V) promoted endothelial cell spreading and migration. Cell spreading on FN-C/H-V, as well as on FN and the 33/66-kD fragments, was associated with the formation of a well developed actin cytoskeleton and the formation of focal contacts. FN-C/H-V (but not scrambled FN-C/H-V) inhibited cell spreading on FN and the 33/66-kD fragments in a concentration-dependent manner. FN-C/H-V had a modest effect on the adhesion of a clonal population of rat heart endothelial cells (RHE-1A) to the 33/66-kD fragments of FN and no effect on RHE-1A cell adhesion to FN. These findings suggest that peptide FN-C/H-V is unique among this group of peptides derived from the 33/66-kD heparin-binding fragments of FN in its ability to promote the adhesion, spreading, and migration of vascular endothelial cells and further suggest that the sequence defined by this peptide plays an important role in vascular endothelial cell interactions with the 33/66-kD fragments of FN. PMID- 7788882 TI - Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease. AB - Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine if PAF synthesis is elevated in damaged coronary arteries after a sustained period of cyclic flow variation (CFV), a phenomenon caused by alternating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anterior descending coronary arteries (LADs) of 10 dogs. After 8 hours of CFV, the section of damaged LAD containing the thrombus and control sections of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purified by silica column chromatography and high-performance liquid chromatography and assayed by both a rabbit platelet bioassay and a PAF radioimmunoassay. With the platelet bioassay, PAF levels of 8.9 +/- 4.0 (range, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF receptor antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3 +/- 12.9 (range, 4.5 to 41.8) pg/mg wet wt were observed in the LADs. Overall, these PAF levels were 3- to 64-fold higher than in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PAF in blood samples taken from the LAD and the aorta (control) failed to demonstrate any site specific increase of PAF in the blood. In related experiments, PAF was also measured in 23 endarterectomy samples taken from the coronary arteries of 16 patients with severe atherosclerosis. The PAF levels in these samples were highly variable (2.9 +/- 2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissue mass, suggesting that PAF is affected by factors other than the simple presence of atherosclerotic tissue in the vessel. These findings provide direct evidence that PAF is synthesized locally at the site of endothelial injury during thrombosis and that PAF accumulates in the atherosclerotic plaque of some patients with advanced coronary artery disease. PMID- 7788883 TI - Localization of atrial natriuretic factor receptors in the mesenteric arterial bed. Comparison with angiotensin II and endothelin receptors. AB - Although receptors for atrial natriuretic factor (ANF) and angiotensin II (Ang II) have been reported in rat mesenteric arteries, both peptides induce weak biological responses. Endothelin-1 (ET-1) evokes a potent vasoconstriction in the mesenteric artery. To identify the tissue localization of ANF, Ang II, and ET-1 receptors, radioligand binding experiments with 125I-ANF, 125I-[Sar1,Ile8]Ang II, and 125I-ET-1 were performed in defatted mesenteric arteries and in the surrounding adipose tissue. 125I-ANF binding assays in adipose tissue showed a single class of high-affinity binding sites (Bmax, 420 +/- 16 fmol/mg protein; Kd, 343 +/- 16 pmol/L). In vascular membranes, most 125I-ANF binding was nonspecific. The majority of receptors present in adipose tissue recognized ANF, C-type natriuretic peptide (CNP), and des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANF-(4- 23) (C-ANF) with close affinities, with C-ANF competing for > 98% of the binding sites. In adipocytes, ANF and CNP stimulated cGMP generation. cGMP production by mesenteric arteries was stimulated by sodium nitroprusside but not by ANF or CNP. Autoradiographic localization of 125I-ANF and 125I-ET-1 showed that in the case of ANF, most specific binding occurred in adipocytes, whereas for ET-1, specific binding was present in both adipose tissue and mesenteric arteries. Cross-linking of 125I-ANF followed by SDS-PAGE revealed two receptor species of 130 and 70 kD in adipose membranes and none in vascular tissue. Both were completely displaced by ANF, CNP, and C-ANF. 125I-[Sar1,Ile8]Ang II binding assays in adipose tissue exhibited a single class of binding sites (Bmax, 211 +/- 4 fmol/mg protein; Kd, 520 +/- 10 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788884 TI - Regulation of aldosterone biosynthesis by adrenal renin is mediated through AT1 receptors in renin transgenic rats. AB - The transgenic (TG) rat (mREN2)27 is characterized by overexpression of the additional mouse Ren-2d gene in the adrenal cortex with marked suppression of renal renin. We have previously shown that in salt-depleted TG rats enhanced activation of mineralocorticoid biosynthesis is associated with selective stimulation of adrenal renin. To investigate whether the local renin-angiotensin system regulates aldosterone biosynthesis in the adrenal cortex of TG rats, we studied the effects of the AT1-angiotensin subtype receptor antagonist DuP 753 on aldosterone production in 5-week-old TG rats during salt restriction. All the rats (n = 56) were shifted from regular chow to a diet containing only 0.04% NaCl for 1 week. The AT1-receptor antagonist DuP 753 (10 mg/kg per day in drinking water) was administered to 27 of these rats during low-salt diet. Subgroups of rats were killed at 0,4, and 7 days. Low-salt diet increased both adrenal renin activity (from 31 +/- 3 to 77 +/- 4 and 85 +/- 2 ng angiotensin I.h-1.mg protein 1 at 4 and 7 days, respectively; P < .001) and mRNA (by 68.4 +/- 10% and 80 +/- 17% from baseline, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788885 TI - L-methionine augments mammalian myocardial contraction by sensitizing the myofilament to Ca2+. AB - L-Methionine is an essential amino acid that has been reported to have a potent positive inotropic effect on the mammalian myocardium. We studied the mechanisms of the inotropic effect in ventricular myocardium from the rabbit. In the isolated coronary-perfused whole heart, L-methionine in a millimolar range exerted concentration-dependent positive inotropic effects on the isovolumic left ventricle, which were associated with negative lusitropic effects (prolonged time course of relaxation). The chronotropic state and the coronary perfusion pressure were not affected. These complex effects on the isolated whole heart were not blocked by pretreatment with (mumol/L) propranolol 1, prazosin 1, carbachol 3, staurosporine 1, or [Ser1,Ile8]angiotensin II 0.1. To further study the subcellular mechanisms, isolated ventricular papillary muscles from the same species were loaded with a bioluminescent indicator, aequorin, to monitor [Ca2+]i. In the presence of 3 mmol/L L-methionine, the isometric tension showed a similar combination of the positive inotropic and negative lusitropic effects as observed in the whole heart. In contrast, the simultaneously recorded intracellular Ca2+ signals did not increase in amplitude but instead decreased. The [Ca2+]i-tension relation shifted to the left compared with that obtained in response to [Ca2+]o. In saponin (250 micrograms/mL)-treated skinned preparations, 3 mmol/L L-methionine also shifted the force-pCa curve to the left by 0.16 pCa units. This is the first demonstration that an essential amino acid directly acts on the myofilaments and modulates their responsiveness to Ca2+, thereby producing a positive inotropic effect. PMID- 7788887 TI - Expression of a mutation causing hypertrophic cardiomyopathy disrupts sarcomere assembly in adult feline cardiac myocytes. AB - Mutations in the beta-myosin heavy chain (beta MyHC) induce hypertrophic cardiomyopathy (HCM), cardiac hypertrophy, and sarcomere disarray, with the latter being the characteristic hallmark. Thus, we sought to determine whether expression of mutant beta MyHC in adult feline cardiac myocytes, a species known to develop HCM with a phenotype identical to that in humans, induces sarcomere disarray. A full-length beta MyHC cDNA was cloned from a human heart cDNA library, and an HCM-causing mutation (Arg403Gln) was induced in the beta MyHC cDNA by site-directed mutagenesis using polymerase chain reaction (PCR). The normal and mutant beta MyHC cDNAs were cloned into p delta E1spIB shuttle vector, downstream from a cytomegalovirus (CMV) promoter. Replication-deficient recombinant adenoviral constructs (Ad5/CMV/beta MyHC-N and Ad5/CMV/beta MyHC-403) were generated through homologous recombination of p delta E1spIB/CMV/beta MyHC-N or Ad5/CMV/beta MyHC-403 and pBHG10 after cotransfection in 293 host cells. Infection of COS-1 cells with the beta MyHC construct resulted in the expression of a full-length myosin protein. Efficiency of infection of isolated adult cardiac myocytes was > 95%. Expression of the beta MyHC constructs into mRNA at 48 hours after infection of feline cardiac myocytes was confirmed by reverse transcription-PCR. The net total protein and beta-myosin synthesis were determined by using the amount of incorporation of [3H]phenylalanine into total protein and beta-myosin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788888 TI - [Nationwide survey of the distribution of human parasites in China--infection with parasite species in human population]. AB - The infection rate of main species of parasites and their character by first nationwide survey of human parasites was made. The overall infection rate of human intestinal parasite and the infection rate of most species of parasites were higher in females than that in males. The infection rate according to the age group, the highest infection rate was found in the group aged 5-14 years. With regard to the relation between parasitic infections and occupations of the infected persons, the highest infection rates of Ascaris lumbricoides were exhibited in school children, of hookworm and Clonorchis sinensis were in halfpeasants and halfmerchant and vegetable grower; of Trichuris trichiura were in fishers, of Giardia lamblia, Entamoeba histolytica and Taenia were in herdsmen and halfherdsmen and halfpeasants. In this survey it is also shown that each nationality has their main species of parasites. The family clustering of some main parasites were proved by some province/autonomous region/municipality. PMID- 7788886 TI - Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport. AB - To investigate whether the energy derived from glycolysis is functionally coupled to Ca2+ active transport in sarcoplasmic reticulum (SR), we determined whether glycolytic enzymes were associated with SR membranes and whether metabolism through these enzymes was capable of supporting 45Ca transport. Sealed right-side out SR vesicles were isolated by step sucrose gradient from rabbit skeletal and cardiac muscle. Intravesicular 45Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca(2+)-ATPase inhibitor thapsigargin. We found that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, phosphoglycerate kinase (PGK), phosphoglyceromutase, enolase, and pyruvate kinase (PK), was associated with SR vesicles from both cardiac and skeletal muscle. Iodoacetic acid, an inhibitor of GAPDH, eliminated 45Ca transport supported by fructose-1,6-diphosphate, the substrate for aldolase, but transport was completely restored by phosphoenolpyruvate (the substrate for PK), indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and PK, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca transport fueled by exogenous ATP but had markedly less effect on 45Ca transport supported by endogenously produced ATP (via glycolysis). Similarly, at very low concentrations of ATP and ADP (10 to 50 nmol/L), ATP that was produced endogenously from ADP and phosphoenolpyruvate supported 15-fold more 45Ca transport than ATP that was supplied exogenously at the same concentration. These results are consistent with functional coupling of glycolytic ATP to Ca2+ transport and support the hypothesis that ATP generated by SR-associated glycolytic enzymes may play an important role in cellular Ca2+ homeostasis by driving the SR Ca2+ pump. PMID- 7788889 TI - [Research on the factors influencing the sporogonic multiplication of Plasmodium vivax in the mosquito vector]. AB - Volunteers with no previous malaria history infected with northern Guangdong isolate of Plasmodium vivax and mosquito vector, Anopheles stephensi, were the objects and materials used in the research. Totally there were 16 volunteers, half of them were infected by mosquito-bite and another half by blood inoculation. Blood was drawn when parasitemia reached a certain level and the erythrocytic forms developed into large trophozoites. Mosquitoes fed on infected blood from 5 and 4 donors of the two groups gave high gland infection rate and high gland indices respectively, but the highest gland indices were got from volunteers infected by mosquito-bite. The time of blood-feeding is important, only those blood samples taken from the people 3 to 8 days after the first onset gave good sporozoite harvest and the gland infection was greatly reduced on the 9th day. During this period (d3-8), the density of gametocyte had obvious influence on the intensity of mosquito infection. When the sex ratio of gametocyte (female:male) was 4:1 or less, the result would be good. For the purpose of reflecting more perfectly the circumstance of the sporogonic multiplication of plasmodium in the mosquito vector, we suggest the concept of gut/gland infection intensity which equals the product of the infection rate and the index of oocyst/positive gland. PMID- 7788890 TI - Purification of 31/32 kDa proteins of adult Schistosoma japonicum as antigens (Sj 31/32) for ELISA and IHA. AB - Major diagnostic proteins of 31/32 kDa were purified from soluble adult worm homogenate of Schistosoma japonicum using AcA ultragel chromatography and additional treatments. The purity of the isolated antigenic proteins (Sj 31/32) was demonstrated by SDS-PAGE and Western blotting technique. The antigens showed a negative reaction when stained by PAS and remained active after treatment with sodium periodate, moving toward anode in the electrophoretic field. These purified antigens were used for detecting the specific antibody in sera from patients with schistosomiasis japonica by ELISA and IHA. As compared with SEA, Sj 31/32 kDa was found as sensitive as but much more specific than SEA in immunodiagnosis. PMID- 7788892 TI - [Dynamics of IL-2 and IFN-gamma levels induced by sea or Con A in spleen cells of Schistosoma japonicum-infected mice]. AB - The capacity of mitogen Con A and SEA-stimulated spleen cells to produce cytokines IFN-gamma and IL-2 was studied in S. japonicum-infected mice every two weeks from 0 to 14 wk after infection. The results showed that the levels of these two cytokines began to rise at the 4th wk after infection and reached a peak level at 6-8 wk, then declined to the levels similar to those pre-infection at 12-14 wk after infection. The IFN-gamma level reached the peak earlier than the IL-2 level. The dynamics of cytokine level in both mitogen and antigen stimulated group was similar. The results suggest that IL-2 and IFN-gamma might be the essential cytokines involved in egg granuloma formation in schistosomiasis japonica. PMID- 7788891 TI - [In vitro effect of metronidazole ester on Trichomonas vaginalis and Entamoeba histolytica]. AB - Metronidazole ester, a new nitroimidazole drug, was synthesized by the Department of Physical Chemistry, School of Pharmacy, Shanghai Medical University. The trichomonadicidal and amoebicidal activity of metronidazole ester was evaluated in vitro by the cultivation of Trichomonas vaginalis and Entamoeba histolytica at different drug concentrations. The results indicated that the 100% lethal concentration for T. vaginalis and E. histolytica was 2.6 micrograms/ml and 40 micrograms/ml, respectively after incubation with metronidazole ester for 48 h. In comparison with metronidazole, the effect of metronidazole ester for both protozoa was similar. PMID- 7788893 TI - [Studies on amino acid and chemical element in five species of filariae]. AB - Five species of human and domestic animal filariae (B. m, S. d, S. l, S. e, D. i) after lyophilization and hydrolysis were resolved using HPLC and type WFX-IB AAS to determine amino acid (AA) and microelement (ME) content, respectively. The results showed that there were 16 and 17 AA in B. malayi and the animal filariae, respectively. Among AA, the total amount (microgram/mg dry wt.) was markedly higher in animal filariae than that in B. malayi in which the content of acidic and aliphatic AA was significantly higher than those of basic and aromatic AA, respectively. Among five ME (Zn, Cu, Fe, Mn, Cd) and two microelements (Ca, Mg) found in all these filariae. Zn Content was the predominant ME and Ca was much more than Mg. PMID- 7788894 TI - [Preparation and characterization of monoclonal antibodies against esterase of malathion-resistant Culex quinquefasciatus]. AB - Five clones of monoclonal antibodies (McAbs) were generated from BALB/c mice which were activized with PPD and immunized with esterases extracted from malathion-resistant Culex quinquefasciatus. All 5 clones of McAbs belonged to the IgG1 subtype, additive index (A.I.) of every two McAbs did not exceeded 50%. After a 1 h of incubation, the McAbs at the titer of 1:1,000 completely inhibited the activity of the amplified esterases. Of 8 strains of adult mosquitoes studied by Western-blot assay, all exhibited the 64 kDa esterase band recognized by the McAbs, six (SP, FS, SH, CD, RD, RM) showed more bands of different MW (43-60 kDa), the higher the organophosphorus resistant level, the more and the denser the bands. The above McAbs had little or no effect against the esterases of dimethrin-resistant strain and the larva stage of malathion-resistant Culex quinquefasciatus. PMID- 7788895 TI - Scanning electron microscope observation on tegumental alteration of Schistosoma japonicum induced by levo- and dextro-praziquantel. AB - When mice infected with Schistosoma japonicum for 35 d were treated ig with levo praziquantel (L-Pra) 150 mg.kg-1 or dextro-praziquantel (D-Pra) 150-600 mg.kg-1, the alterations of the worm tegument were examined by scanning electron microscopy within 1-24 h after administration. The results showed that L-Pra induced apparent and extensive damage on the worm surface including severe swelling, fusion, erosion and peeling of tegument accompanied by attachment of the host leukocytes. The discoid-like sensory structures usually showed swelling, deformation and collapse. With D-Pra 150 mg.kg-1, only slight damage of tegument was seen. When the dose was increased to 600 mg.kg-1, the damage of worm tegument was similar to that induced by L-Pra 150 mg.kg-1 but the intensity of the damage was slighter as compared to that induced by L-Pra. The results suggested that the actions of the 2 optical enantiomers of praziquantel were different in quantity but not in quality. PMID- 7788896 TI - [Pathological changes in the livers of rabbits infected with schistosome cercariae and treated with artemether or praziquantel in the early stage of infection]. AB - When rabbits infected with Schistosoma japonicum cercariae for 7 d were treated ig with artemether (Art) 30 mg.kg-1, and repeated at 1-wk intervals (i.e. on d 14, 21, 28 after infection) for 4 times, dead worms were found in the liver sections, but no egg or egg granuloma was detected. In infected rabbits treated repeatedly with the above-mentioned dosage of Art at 2-wk intervals (i.e. on d 21, 35, 49) after the first dosing on d 7 after infection, few eggs and egg granulomas were seen occasionally. In another experiment, praziquantel (Pra) 40 mg.kg-1 was given ig to rabbits on d 21 after infection and the same dosage was administered repeatedly at 1- or 2-wk intervals for 2 times, the numbers of eggs and egg granulomas detected in the liver sections of these 2 groups were much less as compared with the control. In the latter group treated at 2-wk intervals, only degenerated eggs and egg granulomas were detected occasionally in the liver sections. The results indicate that if Art or Pra was given to rabbits in the early stage after infection, no apparent or only slight damage of the liver induced by the eggs was seen due to the fact that most or even all of the female worms were killed. PMID- 7788897 TI - [Observation on antibody levels of rabbits infected with single sex cercariae of Schistosoma japonicum]. AB - Nine rabbits infected with male S. japonicum cercariae (worm recovery 15-133, mean 53.1) and 9 rabbits infected with female cercariae (worm recovery 1-102, mean 36.1) were bled periodically until 1 year post-infection. The sera were tested by ELISA, LA and CHR for antibody detection. Results showed that the positive rates were 88.9%, 55.6% and 83.3%, respectively. The duration of positive reaction was 3-51 wk post-infection for ELISA, 4-17 wk for LA and 2-35 wk for CHR and the fluctuated results were obtained in ELISA while positive CHR and LA results usually remained stable. The above-mentioned results suggest that antibody detection methods should not be neglected due to its sensitivity although antigen detection methods are considered more favorable. For the surveillance of schistosomiasis in endemic areas where schistosomiasis is under control, antibody detection methods are still worthy of recommending for case finding of new infections. PMID- 7788898 TI - [Efficacy of praziquantel combined with albendazole in the treatment of clonorchiasis]. AB - This paper reported on the clinical efficacy of praziquantel-albendazole combination in the treatment of clonorchiasis in Guangxi. Two hundred and two cases were divided into three groups. The first group comprised 66 cases who were treated with praziquantel at 180 mg/kg bwt for three days. The second group consisted of 62 cases who were treated with albendazole at 90 mg/kg bwt for three days. In the third group, 74 cases were treated with 90 mg/kg bwt praziquantel plus 45 mg/kg albendazole for three days. The results showed that the negative conversion rates were 98.5%, 61.3% and 87.8% in groups one, two and three, respectively, one month after treatment. In some cases who continued to be egg positive, the reduction rates in faecal egg counts were 99.7%, 65.0% and 97.3%, respectively. Although the cure rate in group three was not as high as in group one, the side effects were more mild and transient and the cost of treatment could be reduced by 60% as compared with group one. In cases with light and moderate infections, the praziquantel-albendazole combination proved more effective. In addition, the praziquantel-albendazole combination was also highly effective for treating those cases who were infected with Ascaris, Trichuris or hookworm. PMID- 7788899 TI - [A clinicopathological study of eighteen autopsy cases with acquired toxoplasmosis]. AB - Eighteen autopsy cases of acquired toxoplasmosis in New York City were studied. Seventeen cases were with acquired immunodeficiency syndrome (AIDS) and one patient with Hodgkin's disease. All 18 cases involved the brain and nine of them disseminated to the heart (8 cases), lung (4 cases), pancreas (3 cases), alimentary tract (2 cases) and urogenital organs (3 cases). The authors divided the acquired toxoplasmosis into (1) immunocompetent, (2) immunocompromised and (3) immunodeficient types. The autopsy findings showed that the brain, heart and lung were the most susceptible organs. Pseudocysts were also found in lungs and alimentary tract, suggesting an autoinfection by swallowing sputum containing Toxoplasma. Toxoplasma in the urogenital organs might become a source for sexual transmitted toxoplasmosis. PMID- 7788900 TI - [Effects of different fixatives for Trichomonas vaginalis in indirect fluorescent antibody test]. AB - This paper dealt with the effects of different fixatives for Trichomonas vaginalis in indirect fluorescent antibody test. T. vaginalis fixed by formalin, methanol or alcohol displayed clear flagella. The parasites fixed by methanol and alcohol showed specific ring-like fluorescence with 1-2 bright dots. Antigen slides prepared from different Trichomonas strains, different number of parasites and anti-Trichomonas vaginalis McAb strains in IFA presented different results. Antigen slides showed the best results when using parasites at concentrations of 1.2 x 10(6) cells/ml or 2.4 x 10(5) cells/ml. Antigen preparations stored at 4 degrees C or -20 degrees C remained reactive throughout the experimental period of three months. PMID- 7788901 TI - [Current malaria stratification in China]. AB - During the past 30 years since 1958 when malaria stratification was first made, a great change in malaria situation has occurred. The original stratification can not represent the current status of malaria distribution. Therefore, it needs to be redivided so as to provide basis for future malaria control work. Taking species of mosquito vector and malaria incidence as the main indices and making reference to the natural geographical division, the current malaria endemic area in China can be divided into four regions, i.e. (1) Western region: it is mostly a natural non-endemic area, except some limited areas with sporadic cases in Xinjiang Autonomous Region; (2) Northern region: the whole north-eastern and partial northern China belong to the areas where malaria has been basically eliminated; but sporadic occurrence still exist in most part of the northern China; (3) Central region: it is mostly a hypo-endemic area, only a small part has meso-endemicity; (4) Southern region: nearly 50% has meso-endemicity and the other 50% has hypo-endemicity. The demarcation line of natural non-endemic areas and the areas where malaria has been basically eliminated has been defined. PMID- 7788902 TI - AHA president's letter. PMID- 7788903 TI - Role of endogenous endothelin-1 in experimental renal hypertension in dogs. AB - BACKGROUND: Endothelin-1, a vasoconstrictive peptide released by endothelium, may be involved in the pathophysiology of hypertension. The goal of the present study was to evaluate the role of endogenous endothelin-1 in renal hypertension in dogs. The model of hypertension consisted of silk tissue wrapping of the left kidney, which produced hypertension associated with perinephritis after 6 to 8 weeks. METHODS AND RESULTS: Thirty-two anesthetized open chest dogs were studied randomly: 8 dogs with perinephritic hypertension received the nonpeptidic ETA-ETB receptor antagonist bosentan (group 1); 8 other hypertensive dogs received the vehicle solution (group 2); 8 healthy dogs received bosentan (group 3); and 8 healthy dogs received the vehicle solution (group 4). Bosentan was injected as an intravenous bolus (3 mg/kg) followed by a 1-hour infusion at a rate of 7 mg.kg 1.h-1. In hypertensive dogs, bosentan produced a similar decrease (P = .0001) of both left ventricular systolic and mean aortic pressures, which averaged 38 mm Hg (-22% and -24%, respectively). These parameters remained unchanged with the vehicle solution. Left ventricular end-diastolic and left atrial pressures also declined significantly with bosentan (P = .0005 and P < .05, respectively). Left ventricular lengths tended to decrease. The other cardiovascular parameters (heart rate, peak [+]dP/dt, time constant of relaxation, and coronary vascular resistance) did not change significantly. In healthy dogs, bosentan decreased mean aortic pressure by 19 mm Hg (P = .004). Vehicle solution had no effect. Plasma endothelin-1 levels, similar under basal conditions in healthy and hypertensive dogs, increased 30-fold with bosentan (P = .0001). CONCLUSIONS: Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. This role of endothelin-1 is unrelated to its plasma levels. The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction. PMID- 7788904 TI - Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia-inducible direct angiogenic factor. Upregulation of VEGF is thought to mediate many of the angiogenic effects of growth factors that are not direct endothelial cell mitogens. Like VEGF, basic fibroblast growth factor (bFGF) is considered to induce angiogenesis by a direct effect on endothelial cells. This study investigated the possibility that bFGF may also act indirectly by regulating VEGF expression in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Incubation of confluent and quiescent cultures of rabbit VSMCs with bFGF caused a time- and concentration-dependent increase in steady-state levels of VEGF mRNA, as analyzed by Northern blot hybridization. Exposure of VSMCs to a threshold hypoxic stimulus (2.5% O2) caused a modest increase in VEGF mRNA levels. However, the combination of 2.5% O2 with bFGF had a marked synergistic effect. This effect was specific for VEGF as hypoxia did not enhance bFGF-induced expression of the proto-oncogene c-myc. Synergistic upregulation of VEGF mRNA expression also was observed between hypoxia and TGF-beta 1. CONCLUSIONS: These results suggest that bFGF may promote angiogenesis both by a direct effect on endothelial cells and also indirectly by the upregulation of VEGF in VSMCs. The synergy demonstrated between hypoxia and either bFGF or TGF-beta 1 suggests that multiple diverse stimuli may interact via the upregulation of VEGF expression in VSMCs to amplify the angiogenic response. PMID- 7788905 TI - Role of endothelin-1 in beagles with dehydromonocrotaline-induced pulmonary hypertension. AB - BACKGROUND: Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH. METHODS AND RESULTS: Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6 +/- 2.3 to 35.9 +/- 7.1 mm Hg and from 1.24 +/- 0.25 to 3.25 +/- 0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles. CONCLUSIONS: These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors. PMID- 7788906 TI - Heterogeneities in [K+]o and TQ potential and the inducibility of ventricular fibrillation during acute regional ischemia in the isolated perfused porcine heart. AB - BACKGROUND: The relation between the inducibility of ventricular fibrillation (VF) and heterogeneity of the extracellular potassium concentration ([K+]o) and of TQ potential is unknown. METHODS AND RESULTS: Data from 78 epicardial DC electrodes or from up to 32 intramural K+ electrodes were acquired simultaneously. Induction of VF was attempted with one or two ventricular premature beats induced in normal myocardium in isolated porcine hearts during (1) regional perfusion of the left anterior descending artery (LAD) with a normoxic, hyperkalemic solution ([K+] 6 to 19.6 mmol/L), (2) simulated ischemia, ie, LAD perfusion with a glucose-free, hypoxic solution ([K+] 4 to 16 mmol/L, PO2 < 5 mm Hg, pH 6.98), and (3) regional ischemia produced by stopping LAD flow. During normoxic, hyperkalemic LAD perfusion, no VF could be induced (12 interventions, 7 hearts). During simulated ischemia (27 interventions), VF could be induced only when [K+]o was between 8 and 13.5 mmol/L. After 5 minutes of true regional ischemia, more sites with [K+]o between 8 and 13.5 mmol/L were present than after 10 minutes. VF could be induced with 1 ventricular premature beat in 11 of 17 interventions after 5 minutes and in 0 of 14 interventions after 10 minutes of ischemia (P < .001). Regional simulated ischemia presents a relatively homogeneous condition compared with 5 minutes of regional ischemia (SD +/- SEM of TQ potential in LAD tissue, 0.9 +/- 0.05 versus 2.1 +/- 0.13 mV, respectively). True ischemia superimposed on regional simulated ischemia caused the rapid development of heterogeneities in [K+]o and TQ potential and caused VF after 45 +/- 7 seconds in all interventions. Activation maps of induction of VF suggest a different mechanism of unidirectional block during simulated ischemia from that in true ischemia. CONCLUSIONS: (1) In the presence of hypoxia and acidosis, [K+]o between 8 and 13.5 mmol/L provides the conditions necessary for the induction of VF; (2) after 5 minutes of ischemia, these conditions are present in a larger area and inducibility of VF is higher than after 10 minutes of ischemia; and (3) small heterogeneities within the intermediate K(+)-concentration domain (8 to 13.5 mmol/L) are associated with high inducibility of VF. PMID- 7788907 TI - Effects of load manipulations, heart rate, and contractility on left ventricular apical rotation. An experimental study in anesthetized dogs. AB - BACKGROUND: Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured. METHODS AND RESULTS: Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61 +/- 0.06 degrees/percent change; intercept, -60.1 +/- 6.2 degrees; n = 10) that differed from the end-systolic (ES) relation (slope, 1.36 +/- 0.27 degree/percent change; intercept, -132.5 +/- 24.9 degrees; P < .005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation-volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period. CONCLUSIONS: The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation. PMID- 7788908 TI - Genetic approaches to cardiovascular disease. Supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. AB - BACKGROUND: Although family history can be an important risk factor for cardiovascular disease, relatively little is known about the nature of specific genetic risk factors. One approach to this problem is to identify and characterize genes responsible for inherited disorders in the hope that this information will also provide mechanistic insight into common forms of cardiovascular disease. METHODS AND RESULTS: Over the last decade, it has become possible to identify genes that cause human disease by use of the techniques of molecular genetics, specifically genetic linkage analysis, positional cloning, and mutational analyses. We have used these techniques to study three inherited cardiovascular disorders: supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. We have discovered that the vascular pathology of supravalvular aortic stenosis and Williams syndrome results from mutations involving the elastin gene on chromosome 7q11.23. These mutations include intragenic deletions, translocations, and complete deletion of the elastin gene, suggesting that a quantitative reduction in elastin during vascular development is pathogenically important. To date, only the elastin gene has proved important for supravalvular aortic stenosis. By contrast, genetic linkage analyses in families with long-QT syndrome indicate that at least four distinct genes can cause this disorder. We have identified three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Recently, we demonstrated that mutations in a putative cardiac potassium channel gene, HERG, are responsible for the chromosome 7-linked form of long-QT syndrome, whereas mutations in the cardiac sodium channel gene SCN5A cause the chromosome 3-linked form of this disorder. HERG mutations and potassium channel biophysics suggest a dominant-negative molecular mechanism and reduced repolarization currents. By contrast, SCN5A mutations probably cause subtle alterations of cardiac sodium channel function and prolonged depolarizing currents. CONCLUSIONS: Molecular genetic analyses of long-QT syndrome, supravalvular aortic stenosis, and Williams syndrome have begun to unravel the mechanisms underlying these inherited disorders. Rapid genetic testing for Williams syndrome is now available using a simple cytogenetic test, fluorescence in situ hybridization, but additional work will be required for long-QT syndrome and autosomal-dominant supravalvular aortic stenosis. Improved diagnosis and mechanistic understanding of these disorders should lead to rational treatment and prevention. PMID- 7788909 TI - Images in cardiovascular medicine. Permanent pacemaker wire vegetation in the right atrium. PMID- 7788910 TI - Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by 31P magnetic resonance spectroscopy. AB - BACKGROUND: 31P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. METHODS AND RESULTS: Forty-one subjects with stenosis of the left anterior descending coronary artery (> 50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+], n = 29) who demonstrated redistribution at late image and a fixed 201Tl defect group (RD[-], n = 12). While the subjects lay supine within the magnet, 31P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (+/- SD) PCr at rest (C, 12.14 +/- 4.25 > RD[+], 7.64 +/- 3.00 > RD[-], 3.94 +/- 2.21 mumol/g wet heart tissue, P < .05) as well as a significant decrease in ATP in the RD(-) group (C, 7.72 +/- 2.97; RD[+], 6.35 +/- 3.17 > RD[-], 4.35 +/- 1.52 mumol/g wet heart tissue, P < .05). CONCLUSIONS: Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed 201Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by 31P MRS is a clinically important method for the evaluation of myocardial viability. PMID- 7788911 TI - Preventing heart attack and death in patients with coronary disease. PMID- 7788912 TI - 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. AB - BACKGROUND: Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17 beta-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17 beta-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease. METHODS AND RESULTS: We studied nine postmenopausal women 59 +/- 3 years old, mean +/- SEM, and seven men 52 +/- 4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 micrograms/min before and 20 minutes after intracoronary administration of 2.5 micrograms of 17 beta-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary artery diameter were measured by quantitative angiography, and changes in coronary blood flow were measured with an intracoronary Doppler catheter. In female patients, acetylcholine 1.6 and 16 micrograms/min caused constriction before the administration of 17 beta estradiol (-6 +/- 2% and -8 +/- 5%, respectively, compared with baseline). This constrictor response was converted to dilatation after intracoronary administration of 17 beta-estradiol (+8 +/- 2% and +9 +/- 3%, respectively; P < .01 before versus after estrogen). Acetylcholine 1.6 and 16 micrograms/min increased coronary blood flow before and after the infusion of 17 beta-estradiol. However, the mean acetylcholine-induced increases in coronary flow were significantly greater (P < .009) after (126 +/- 37% and 248 +/- 89%, respectively) than before (94 +/- 31% and 143 +/- 49% mL/min, respectively) the administration of 17 beta-estradiol. 17 beta-Estradiol alone had no significant effect on coronary diameter or coronary blood flow (P > .05). Isosorbide dinitrate (1 mg) caused dilatation of the coronary arteries by 11 +/- 2% (P < .005). In men, acetylcholine 1.6 and 16 micrograms/min caused constriction both before and after the administration of 17 beta-estradiol and caused similar increases in coronary blood flow both before and after the intracoronary administration of 17 beta-estradiol. Infusion of intracoronary placebo in six female control patients 55 +/- 3 years old and six male control patients 56 +/- 3 years old did not change coronary diameter responses or coronary blood flow responses to acetylcholine. CONCLUSIONS: 17 beta-Estradiol modulates acetylcholine-induced coronary artery responses of female but not male atherosclerotic coronary arteries in vivo. These human data confirm reports from studies in cynomolgus monkeys that estrogen modulates the responses of atherosclerotic coronary arteries. An enhancement of endothelium-dependent relaxation by natural estrogen (as used in most hormone replacement therapy) may be important in postmenopausal women with established coronary heart disease and may contribute to the acute effect of 17 beta-estradiol on blood flow and its long-term protective effect on the development of coronary artery disease. PMID- 7788913 TI - Fibrinogen after coronary angioplasty as a risk factor for restenosis. AB - BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. METHODS AND RESULTS: In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis > 50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (> 0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration > 3.5 g/L at follow-up had higher restenosis rates than patients with a concentration < 3.5 g/L: 55% versus 22% (P = .001), 68% versus 31% (P = .002), 63% versus 37% (P = .01), and 74% versus 26% (P = .002) for definitions 1 through 4, respectively. The loss index was lower (P = .003) and the net gain higher (P = .03) in patients with a fibrinogen level < 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index (r = .41; P < .0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. CONCLUSIONS: An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis. PMID- 7788914 TI - Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia. AB - BACKGROUND: Myocardial fractional flow reserve (FFRmyo) is a functional index of stenosis severity that can be derived from intracoronary pressure measurements performed during maximal vasodilatation. It is defined as the maximal myocardial perfusion during hyperemia in the presence of a stenosis in the epicardial artery expressed as a fraction of its normal maximal expected value. To determine threshold values of FFRmyo, of hyperemic translesional pressure gradient (delta P(max)), and of resting translesional pressure gradient (delta P(rest)) that are uniformly associated with exercise-induced ischemia, we studied the relation between these pressure-derived indexes and the results of exercise ECG. METHODS AND RESULTS: We studied 60 patients with an isolated lesion in one major epicardial coronary artery, normal left ventricular function, and no left ventricular hypertrophy. Maximal exercise ECG (off anti-ischemic medication) was performed within 6 hours before catheterization. Intracoronary pressure measurements were taken at rest and during hyperemia with a pressure monitoring guide wire. ST-segment depressions at peak exercise (considered abnormal when > or = 0.1 mV) were compared with FFRmyo, delta P(max), and delta P(rest). Thirty seven patients had an abnormal and 23 patients a normal exercise ECG. A significant linear correlation was found between the magnitude of ST-segment depressions and both FFRmyo and delta P(max) (r = -.75, SEE = 0.53; r = .71, SEE = 0.56). A weaker correlation was noted between ST-segment depressions and delta P(rest) (r = .53, SEE = 0.67). Sensitivity and specificity curves were constructed for the prediction of an abnormal exercise ECG for the three pressure derived indexes. The values that most accurately predicted an abnormal exercise ECG were 66% for FFRmyo, 31 mm Hg for delta P(max), and 12 mm Hg for delta P(rest). No patient with a FFRmyo value > 72% showed an abnormal exercise ECG. In addition, receiver operating characteristic curves demonstrated a greater accuracy of FFRmyo and of delta P(max) than of delta P(rest) for predicting the results of the exercise ECG. CONCLUSIONS: In the present study, cutoff values of FFRmyo and translesional pressure gradients are established from the relation between intracoronary pressure-derived indexes and ECG signs of myocardial ischemia during maximal exercise. These values can be helpful for clinical decision making in cases with dubious angiographic results. Furthermore, our data support the concept that stenosis physiology is better reflected by hyperemic than by basal measurements. PMID- 7788915 TI - Dissociation between exertional symptoms and circulatory function in patients with heart failure. AB - BACKGROUND: Patients with heart failure frequently report exertional dyspnea and fatigue. These symptoms are usually attributed to circulatory dysfunction and therefore are typically treated with cardiovascular medications. Serial assessment of exertional symptoms has also become the principal method used to assess drug efficacy in heart failure. Nevertheless, the relation between exertional symptoms in heart failure and circulatory dysfunction remains uncertain. METHODS AND RESULTS: This study was undertaken to investigate the relation between exertional symptoms, ventilatory and skeletal muscle dysfunction, and circulatory function in patients with heart failure. To this end, 52 ambulatory patients with heart failure underwent hemodynamic monitoring during maximal treadmill exercise testing. During exercise, the severity of dyspnea and fatigue was evaluated on a scale of 6 to 20 (Borg scale). The level of perceived exercise intolerance during daily activities was evaluated with the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. Maximal treadmill exercise increased the VO2 to 13.4 +/- 2.8 mL.min-1.kg 1, the dyspnea score to 15.7 +/- 2.3, the fatigue score to 14.8 +/- 3.4, the pulmonary wedge pressure to 28 +/- 11 mm Hg, and the pulmonary artery lactate concentration to 34.5 +/- 16.3 mg/dL and decreased the pulmonary artery hemoglobin oxygen saturation to 30 +/- 9%. The level of perceived dyspnea had no relation to the pulmonary wedge pressure and correlated only minimally with the level of excessive ventilation (r = 39). The level of perceived fatigue correlated only weakly with blood lactate concentration (r = .55). Eleven patients (21%) exhibited a normal cardiac output and wedge pressure < 20 mm Hg during exercise, 22 (42%) exhibited a normal cardiac output but wedge pressure > 20 mm Hg during exercise, and 19 (37%) exhibited reduced cardiac output and wedge pressure > 20 mm Hg during exercise. Despite these markedly different hemodynamic responses, all three groups exhibited similar levels of fatigue and dyspnea at comparable workloads and had comparable total scores for the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. There was no relation between the Living With Heart Failure Questionnaire and peak exercise VO2 and only a weak correlation between the Dyspnea-Fatigue Index and peak VO2 (r = .48). CONCLUSIONS: The level of exercise intolerance perceived by patients with heart failure has little or no relation to objective measures of circulatory, ventilatory, or metabolic dysfunction during exercise. In patients who report severe exertional symptoms, it may be desirable to directly measure hemodynamic response to exercise to ensure that these symptoms are due to circulatory dysfunction. PMID- 7788916 TI - How do we explain the clinical benefits of estrogen? From bedside to bench. PMID- 7788918 TI - Results of the international study of the implantable pacemaker cardioverter defibrillator. A comparison of epicardial and endocardial lead systems. The Pacemaker-Cardioverter-Defibrillator Investigators. AB - BACKGROUND: The purpose of the present report was to document clinical experience derived from the implantation of 2834 epicardial and endocardial cardioverter defibrillators (ICDs) in 2807 patients who were followed for almost 1 year and to compare the results obtained with the two systems. METHODS AND RESULTS: Patients in the two groups had similar clinical characteristics. More than half of the patients had a total of almost 50,000 spontaneous ventricular tachyarrhythmias that were terminated with equal success (approximately 98%) by epicardial and endocardial ICDs. Lead dislodgement and pocket infection occurred more often with the endocardial than with the epicardial ICD, whereas perioperative mortality was higher with the epicardial ICD than with the endocardial ICD. Mortality from sudden cardiac death was 1.4% in the epicardial ICD group and 0.6% in the endocardial ICD group at 1 year (P = .069). Overall mortality at 1 year was 12.2% and 6.9% for the epicardial and endocardial groups, respectively (P < .001), reflecting the higher surgical mortality for the epicardial system. CONCLUSIONS: The endocardial ICD is as effective as the epicardial ICD but incurs lower perioperative mortality. PMID- 7788917 TI - Provocation of hypotension during head-up tilt testing in subjects with no history of syncope or presyncope. AB - BACKGROUND: Head-up tilt test is increasingly being used to evaluate patients with syncope. This study was designed to evaluate the specificity of head-up tilt testing using different tilt angles and isoproterenol infusion doses in normal volunteers with no prior history of syncope or presyncope. METHODS AND RESULTS: One hundred fifty volunteers were randomized to two groups of 75 each. In group 1, subjects were further randomized to have head-up tilt testing at a 60, 70, or 80 degree angle at baseline followed by repeat tilt testing during a low-dose isoproterenol infusion that increased the heart rate by an average of 20%. In group 2, after having a baseline head-up tilt test at a 70 degree angle for a maximum of 20 minutes, subjects were randomized to have a repeat tilt table testing at a 70 degree angle during a low-dose, 3 micrograms/min, or 5 micrograms/min isoproterenol infusion. In group 1, syncope or presyncope along with hypotension developed in 2 subjects during the baseline test at 60 and 70 degrees of tilt and in 5 subjects during tilting at 80 degrees. The addition of low-dose isoproterenol reduced the specificity minimally from 92% to 88% at both 60 and 70 degrees of tilt but substantially to 60% at an 80 degrees angle. However, 6 of the 10 subjects with a positive test at an 80 degree angle had an abnormal response after 10 minutes of tilt testing. In group 2, using various isoproterenol doses with tilt table testing at a 70 degree angle, low-dose (mean infusion dose, 1.5 +/- 0.45 microgram/min), 3 micrograms/min, and 5 micrograms/min isoproterenol infusions elicited an abnormal response in 1 (4%), 5 (20%), and 14 (56%) of the subjects, respectively. Using multiple logistic regression analysis, head-up tilt testing at an 80 degree angle (P = .01) or during 3 micrograms/min (P = .02) and 5 micrograms/min isoproterenol infusion rates (P < .001) was the most significant predictor of an abnormal response. CONCLUSIONS: Head-up tilt testing at a 60 or 70 degree angle with or without low dose isoproterenol infusion provides an adequate specificity. Caution is needed, however, in interpreting the results if the head-up tilt test at 80 degrees is extended beyond 10 minutes or if high doses of isoproterenol are used. PMID- 7788919 TI - Electrophysiological manifestations of the excitable gap of slow-fast AV nodal reentrant tachycardia demonstrated by single extrastimulation. AB - BACKGROUND: Although AV nodal reentrant tachycardia (AVNRT) is a well-known rhythm disorder, its anatomic substrate and electrophysiological mechanism remain to be defined. Previously, the description of the excitable gap (EG) of AVNRT was based on electrical stimulation performed from sites remote from the reentrant circuit. In the present study, we characterized the EG of AVNRT by atrial extrastimulation close to the putative reentrant circuit in the AV junction. METHODS AND RESULTS: In 16 patients (3 men, 13 women; mean age, 45 +/- 13 years) with inducible slow-fast AVNRT (mean cycle length, 353 +/- 52 ms), single extrastimuli with a 10-ms decrement in the premature coupling interval were delivered from the anterosuperior interatrial septum (fast pathway area) and the posteroinferior interatrial septum (slow pathway area) from late diastole until atrial refractoriness. An EG was considered present when resetting or termination of AVNRT was induced by single atrial extrastimulation. The study showed that the duration of the EG of AVNRT was wide, measuring 121 +/- 56 and 123 +/- 47 ms and occupying 33 +/- 11% and 34 +/- 9% of the tachycardia cycle length during single extrastimulation from the slow pathway area and the fast pathway area, respectively. The resetting pattern most commonly manifested as the sum of the coupling interval and the return cycle being less than a fully compensatory pause (two times the basic tachycardia cycle length). However, patterns equal to and greater than a fully compensatory pause were also observed. Of note, in 2 of the 16 patients, atrial extrastimulation from either the fast or slow pathway area also affected the preceding tachycardia cycle length (HH interval), indicating alteration of the anterograde input. In all patients, the curve derived from plotting the coupling interval of extrastimuli against the return cycle during resetting exhibited an "increasing" pattern. The mode of tachycardia termination usually occurred when the premature atrial impulse was orthodromically blocked in the anterograde slow pathway. CONCLUSIONS: The EG of slow-fast AVNRT is relatively wide, as demonstrated by single atrial extrastimulation from the interatrial septum near the AV junction. Overall, the electrophysiological manifestations of the EG of AVNRT are very similar to those described in AV reciprocating tachycardia incorporating an accessory connection. These findings lend further support to the notion that, in humans, AVNRT involves a reentrant mechanism with a wide excitable gap. PMID- 7788920 TI - Atrial electrogram characteristics in patients with and without atrioventricular nodal reentrant tachycardia. AB - BACKGROUND: Multicomponent atrial electrograms and "slow pathway potentials" are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia. METHODS AND RESULTS: In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of < or = 1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (P < .005 compared with the posterior septum). CONCLUSIONS: The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia. PMID- 7788922 TI - Angiotensin II type 1 receptor blockade inhibits the expression of immediate early genes and fibronectin in rat injured artery. AB - BACKGROUND: Vascular injury activates various kinds of genes, including proto oncogenes, growth factors, and extracellular matrix proteins. However, the significance of activation of these genes in neointimal formation is poorly understood. Angiotensin II type 1 (AT1) receptor antagonist is shown to prevent neointimal formation after vascular injury, although the mechanism is unclear. To understand the molecular mechanism of vascular thickening, we examined the effects of AT1 receptor blockade on the gene expression of proto-oncogenes, transforming growth factor-beta 1 (TGF-beta 1), and extracellular matrix proteins after vascular injury. METHODS AND RESULTS: Endothelial denudation of the left common carotid artery in Sprague-Dawley rats was performed with a Fogarty 2F balloon catheter. TCV-116 (10 mg.kg-1.d-1), a selective nonpeptide AT1 receptor antagonist, or vehicle was administered orally to rats from 1 day before to 14 days after balloon injury. Injured left and uninjured right common carotid arteries were removed from rats at 1, 6, and 24 hours and 3, 7, and 14 days after balloon injury. Tissue mRNA levels were measured with Northern blot analysis using specific cDNA probes and corrected for 18S ribosomal RNA value. Arterial mRNAs for c-fos, c-jun, jun B, jun D, and Egr-1 increased significantly at 1 hour after balloon injury and decreased rapidly. At 6 hours, ornithine decarboxylase (ODC) mRNA expression reached the maximal levels. TGF-beta 1 and fibronectin mRNA levels started to increase at 6 hours after injury and remained enhanced until 7 days after injury. On the other hand, collagen types I, III, and IV and laminin mRNA levels were not significantly increased over 7 days. Treatment with TCV-116 significantly inhibited the induction of mRNAs for c-fos, c-jun, Egr-1, ODC, and fibronectin in injured artery, whereas the increase in TGF-beta 1 gene expression after injury was not prevented by TCV-116. Immunohistological studies indicated that TCV-116 decreased not only the intimal thickening but also the amount of these extracellular matrix proteins in the intima. CONCLUSIONS: The results indicate that AT1 receptor blockade inhibits the induction of immediate-early genes, ODC, and fibronectin in rat injured artery. Thus, inhibition of intimal thickening by AT1 receptor blockade may be mediated at least in part by suppression of multiple genes related to cell growth and migration in the very early phase after vascular injury. PMID- 7788923 TI - Is 31P-NMR spectroscopic imaging a viable approach to assess myocardial viability? PMID- 7788921 TI - Cardiac allograft survival in mice deficient in intercellular adhesion molecule 1. AB - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell adhesion molecule that interacts with the leukocyte beta 2 integrins, lymphocyte function associated antigen-1, and macrophage antigen-1. ICAM-1 is postulated to play a key role in several cell-cell interactions that are important in allograft rejection, including antigen presentation, transendothelial migration of leukocytes, and leukocyte-medicated myocyte injury. METHODS AND RESULTS: Mice homozygous for a gene-targeted mutation of ICAM-1 were used in two different cardiac transplant models to further define the role of ICAM-1 in the process of allograft rejection. In the first model, hearts from newborn mice were implanted in the ear pinnae of H-2-incompatible recipients. In the second model, intra abdominal transplantation by direct vascular anastomosis was performed. Time to rejection was defined by the loss of pulsatile activity assessed by visual inspection in the ear model or by cessation of palpable cardiac impulse in the abdominal model. Allograft survival did not differ significantly between control groups that express normal levels of ICAM-1 and those groups using ICAM-1 deficient mutants as either donors or recipients. Histological examination of rejection of both normal and mutant (ICAM-1-deficient) cardiac allografts revealed similar patterns of infiltration of mononuclear and granulocytic leukocytes and myocyte necrosis. Immunostaining with anti-ICAM-1 antibodies showed ICAM-1-positive infiltrating cells in both mutant (ICAM-1-deficient) and normal allografts, with the graft endothelium negative for ICAM-1 staining in the mutant allografts. CONCLUSIONS: The absence of surface expression of ICAM-1 in the donor allograft or recipient is insufficient to produce a significant impact on cardiac allograft survival. This study highlights the need to understand more precisely the mechanism of action whereby monoclonal antibodies to ICAM-1 prolong cardiac allograft survival before new therapeutic strategies based on gene transfer technology or small molecule inhibitors are developed. Mutant mice with targeted mutations in cell adhesion molecules provide powerful tools to study the complex role that cell adhesion molecules play in the cellular interactions between donor graft tissue and the recipient that culminate in graft rejection. PMID- 7788925 TI - General practitioner follow-up of children undergoing grommet insertion. Can it work? PMID- 7788924 TI - Role of blood doping in the coronary vasoconstrictor response to cocaine. AB - BACKGROUND: The mechanism by which cocaine induces myocardial ischemia remains controversial. Most prior studies have postulated that cocaine-induced coronary vasoconstriction limits myocardial oxygen delivery during times of increased myocardial oxygen demand. METHODS AND RESULTS: To determine the contribution of altered myocardial metabolic demands to the coronary vasoconstrictor effects of intravenous cocaine (COC 1 mg/kg), we studied 13 conscious, chronically instrumented dogs in the intact state and with heart rate held constant with atrial pacing in the presence and absence of beta-adrenergic blockade with propranolol (2 mg/kg) to limit the inotropic and chronotropic effects of cocaine on associated increases in myocardial oxygen consumption. In the intact state, COC caused a prompt increase in coronary blood flow (+30 +/- 3%, P < .01) that returned rapidly to baseline within 10 minutes, whereas coronary vascular resistance did not increase significantly (+17 +/- 6%, P < .05) until 15 minutes after COC. Notably, myocardial oxygen consumption increased (+57 +/- 4%, P < .01) to a greater extent than oxygen delivery (+42 +/- 3%, P < .01) during the first 2.5 minutes, requiring increased oxygen extraction (from 75 +/- 1% to 80 +/- 1%, P < .01), although only transiently. Thereafter, enhanced oxygen delivery matched the required oxygen consumption without further need to extract additional oxygen. Surprisingly, the enhanced oxygen delivery associated with COC in conscious dogs did not depend on persistent increases in coronary blood flow but rather was due to enhanced arterial oxygen content (+22 +/- 4%, P < .01) as a result of a significant "blood doping" effect with associated increases in circulating hemoglobin from 12.1 +/- 0.4 to 14.2 +/- 0.6 g/dL (P < .01), which persisted for 60 minutes. CONCLUSIONS: The myocardial oxygen requirements associated with COC administration have a significant impact on both the magnitude and the mechanism of the coronary vasoconstrictor effects of COC in conscious dogs. Furthermore, the enhanced myocardial oxygen delivery associated with COC administration is not dependent solely on coronary blood flow responses but is due to a significant "blood doping" effect associated with COC. PMID- 7788926 TI - Day case myringoplasty using tragal perichondrium. AB - Day surgery has an ever-increasing role to play in otology. In this study of myringoplasty, tragal perichondrial grafts were placed permeatally as a day case procedure in 32 patients. These are compared with a control group, matched for age and for the size of their perforations, in whom temporalis fascia was grafted via an endaural or postaural incision. The success rate was 94% in the perichondrial group as compared with 84% in the control group (no significant difference P > 0.05). Day case myringoplasty produced less morbidity for the patients and a 40% reduction in theatre time as well as the more obvious savings resulting from a shorter hospital stay. PMID- 7788927 TI - Establishment and characterization of a human cell line from a squamous carcinoma of the tongue. AB - A human squamous carcinoma cell line, PWH-S1, has been established from the metastatic lymph node of a Chinese patient with a squamous cell carcinoma of the tongue. The fibroblast-free culture has been propagated in DMEM supplemented with 10% fetal bovine serum for more than 100 passages. PWH-S1 cells showed anchorage independent growth in 0.3% agar solution. PWH-S1 cell line exhibited a monolayer growth and loss of contact inhibition. The in vitro doubling time of the PWH-S1 cell line was approximately 28 h. PWH-S1 was tumourigenic after inoculation into nude mice. Karyotype analysis showed the chromosome abnormality with a modal number of 69. Electron microscopy demonstrated poorly differentiated neoplastic cells with some features of squamous cell differentiation. No human papillomavirus (type 6, 11, 16, 18, 31) was detected in the PWH-S1 cell line by the polymerase chain reaction. PMID- 7788928 TI - Delay in the diagnosis of oral squamous cell carcinoma. AB - Delay in diagnosis was recorded prospectively in 167 patients with an oral squamous cell carcinoma. The median total delay was 4 months of which two-thirds was patient delay. The corrected survival did not correlate with the total delay. The patient delay was not significantly correlated with tumour or patient factors and the unreliable nature of patient delay information makes such data clinically unusable. In contrast, the professional delay correlated significantly with some of these factors. The delay was longer for women than for men and the older the patient, the longer the delay. The professional delay was longest in patients with small tumours. Thus, registration of the professional delay provides information to be used to improve the diagnostic efficiency of the health care system. PMID- 7788930 TI - Clinical coding in ENT surgery: the Read Codes and clinical terms project. PMID- 7788929 TI - Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide. AB - Budesonide has been used for a number of years as a topical nasal corticosteroid in the treatment of nasal allergy and nasal polyps. Recently, a new device for powder insufflation where no constituents or preservatives are included has been developed (Rhinocort Turbuhaler, Astra Draco AB, Sweden). The present investigation was designed in order to study the efficacy of topical budesonide powder as the only treatment of nasal polyps. A total of 126 patients entered the study. The medical history and clinical recordings included symptoms and signs, a semiquantitative test of smell and measurement of nasal expiratory peak flow index. Medication was either 200 or 400 micrograms of budesonide powder b.i.d. or placebo. After 1 month an overall assessment of treatment efficacy was made to determine whether the treatment had been a success or a failure. The results showed a statistically significant improvement of symptoms and signs in the actively treated groups. The increase in expiratory peak flow index was about 60% in the actively treated groups as opposed to 16% in the placebo group. The overall assessment of treatment efficacy showed success in about 82% of actively treated patients as opposed to about 43% in the placebo group. It is concluded that budesonide powder is useful in the treatment of nasal polyps. PMID- 7788932 TI - A 3-D finite element analysis of the natural frequencies of vibration of a stapes prosthesis replacement reconstruction of the middle ear. AB - In this work, the natural frequencies of vibration of two different stapes prosthesis replacement reconstructions have been analysed using the finite element method. Prosthesis 1 was constructed of fine stainless steel wire and a Teflon base, while prosthesis 2 was made entirely of Teflon. The results have indicated that generally, the first natural frequency of vibration falls as the prostheses become larger and more bulky. However, the fall in the first natural for prosthesis 1 was modest when compared with that of the isolated tympanic membrane. An important variable influencing frequencies and mode of vibration of the reconstruction was the tightness of fit of the prostheses within the remaining ossicular chain. The tightness of fit in this work was modelled as a range of spring constants applied at the stapes pseudo footplate, together with a series of joint elements at the incus tip/prosthesis head for the Teflon implant. When these spring constraints were below approximately 10 N/mm, the reconstruction exhibited normal mode 1 vibration behaviour, but at larger spring values, an abnormal mode 1 became established resembling the normal mode 2 vibration characteristics. The formation of new geometries and surfaces following reconstruction, introduces new constraints between umbo and stapes footplate particularly at the natural/artificial interfaces. These unnatural constraints may inhibit and modify the natural movements normally occurring at the stapes footplate leading to abnormal modes of vibration. PMID- 7788931 TI - Bone-anchored hearing aids in patients with sensorineural hearing loss and persistent otitis externa. AB - Recently, a new bone-conduction hearing aid has become available which can be connected percutaneously to the skull: the bone-anchored hearing aid or BAHA. Several clinical trials have shown its efficacy in patients with a conductive or mixed hearing loss. A second group of potential candidates are patients who suffer from an almost instantaneous skin reaction to any kind of earmould. Three such patients with a predominant sensorineural hearing loss were fitted with a BAHA. The aided free-field thresholds proved to be poor compared with the desired values using prescriptive rules. Speech recognition measured objectively (with tests) and subjectively (with a questionnaire) was comparable or better than with conventional bone-conduction hearing aids. Two patients were using their BAHA all day, whereas the third patient was only using it for a few hours per day. Although it did not produce optimal results, the BAHA seems to be the best solution for these patients. PMID- 7788933 TI - Short- and long-term outcomes of uvulopalatopharyngoplasty for snoring. AB - Uvulopalatopharyngoplasty is a well established and highly successful operation in the treatment of snoring. However, most published data are based on relatively short-term follow-up results. Anecdotal cases of late recurrence of snoring after an initially successful surgical result have been reported but few formal studies have been performed to determine the true magnitude of this problem. We compared the short-term and long-term results on our patients and found the late recurrence rate after a minimum follow-up period of 12 months (range: 12-84 months, mean 31.3 months) to be in the region of 13%. The risk of recurrence was directly related to the body mass index. PMID- 7788934 TI - Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance. AB - p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours. PMID- 7788935 TI - Genetics of familial and non-familial skull base tumours. AB - Many tumours of the skull base, including schwannomas, paragangliomas, meningiomas and anterior pituitary tumours occur both as sporadic tumours and in clear cut familial syndromes. These cancers' highly penetrant dominantly inherited syndromes have proven to be a rich resource for locating tumour genes, most of which are of the tumour suppressor type. Recently, the gene for type 2 neurofibromatosis (NF2) was isolated by the technique of positional cloning. The NF2 gene has now been demonstrated to be involved in the pathogenesis of both familial and non-familial vestibular schwannomas as well as meningiomas. The presence of inactivating mutations within this gene suggests that it acts as a tumour suppressor and the mechanism has been shown to comply with a 'two hit' mutation model. Hereditary tumours constitute a small proportion of all cases, but evidence from studies of tumours such as vestibular schwannoma and meningioma have shown that their genes are also relevant to the much more common non familial forms of the same tumour. This paper briefly describes the approach to locating tumour genes, and reviews our current knowledge regarding the chromosomal location and function of genes responsible for familial tumours involving the skull base. The genetic mechanisms of tumourigenesis are discussed as are the prospects for the development of novel forms of diagnosis and treatment. PMID- 7788936 TI - Chondrosarcoma of the temporal bone. AB - Eight patients with a chondrosarcoma of the temporal bone have been treated at the National Hospital for Neurology and Neurosurgery over a 16-year-period. Patients usually presented with symptoms and signs of lower cranial nerve palsies, though in most cases these resolved after surgery. This result, combined with the fact long-term survival can be achieved, makes surgical treatment of these tumours the best option, as the response to primary radiotherapy is uncertain. Surgical access is difficult, but an infratemporal approach is probably the most satisfactory. The use of post-operative adjuvant radiotherapy may provide some benefit. Long-term follow-up is necessary, and for this magnetic resonance imaging (MRI) is preferable to computed tomography (CT) scanning. PMID- 7788937 TI - Speech discrimination in patients with Bell's palsy and a paralysed stapedius muscle. AB - The contraction of the stapedius muscle results in a frequency dependant attenuation of sound through the middle ear. Idiopathic facial nerve paralysis (Bell's palsy) usually results in a paralysis of the stapedius muscle. This prospective study included 119 patients presenting with Bell's palsy over an 18 month period. After applying exclusion criteria, 80 patients with normal pure tone audiograms underwent speech audiometry. This was performed on presentation and after recovery of the facial nerve palsy. Fifty-six patients (70%) with an absent stapedius reflex showed marked 'roll-over' from means of 98-49% on their speech audiogram. This resolved completely with recovery of the facial nerve palsy and return of the stapedial reflex. To determine whether this effect was due primarily to the paralysis of the stapedius muscle or to an associated polyneuropathy, a second study on six normal patients was done. These patients had both ears (12 in total) tested with speech filtered to simulate a paralysed stapedius muscle. This resulted in a mean 'roll-over' from 90.9 to 59.9%. The magnitude of this roll-over (31%) was only two-thirds of that seen in Bell's palsy patients (49%) with the difference between these means statistically significant (P < 0.05). This suggests that Bell's palsy, usually considered a mononeuropathy, involves certain of the auditory fibres of the eighth nerve and is a polyneuropathy. Stapedius function is important in speech discrimination at higher levels of sound intensity such as speech in noise and severing the stapedius tendon in stapes surgery may affect speech discrimination after successful surgery. PMID- 7788939 TI - The Glasgow benefit plot used to assess the effect of bilateral stapedectomy. AB - The Glasgow benefit plot has encouraged surgeons to look at the results of their surgery from a more functional standpoint rather than in purely technical terms. Our aim was to use the plot to examine the efficacy of second side stapedectomy. A retrospective study of 17 second side stapedectomies showed that the addition of the second operation significantly increased the chances of achieving at least one 'normal' hearing ear and made 'normal' and symmetrical hearing possible. PMID- 7788938 TI - Is otoscopy reliable? A structured teaching method to improve otoscopic accuracy in trainees. AB - Otoscopy is an important skill for primary care physicians and otologists. Until now, training has been by repeated exposure to patients with ear disease. Structured instruction in how to assess an ear has not previously been reported. Not-diseased ears and those with varying types of chronic (suppurative) otitis media were chosen to be photographed as this is an important condition to be able to diagnose and in which pneumatic otoscopy has no role. Two sets of 30 slides of equal difficulty were shown to 10 trainees, one before and one after structured teaching. The overall error rate fell from 44 to 21% (P < 0.001). Most importantly, the error rate in assessing ear activity fell from 35 to 17% (P < 0.05). In conclusion, a structured approach to otoscopy has been shown to improve the diagnostic ability of trainess tested with photographs of ears with chronic otitis media. Such a teaching approach is likely to be equally beneficial to other otological conditions and to live otoscopy. PMID- 7788940 TI - Piriform aperture surgery for alar collapse. AB - The region of maximum resistance in the respiratory tract is in the anterior part of the nose, and this area has been termed the nasal valve. Inspiratory narrowing of this area, known as alar or nasal valve collapse can produce the symptom of obstruction, and may be very difficult to correct. The anatomy and physiology of the nasal valve are discussed followed by the author's technique for correction of a common problem leading to alar collapse; a narrow piriform aperture, which is often associated with a prominent web at the muco-cutaneous junction. PMID- 7788941 TI - Referral patterns in vestibular schwannomas. AB - The investigation and treatment of vestibular schwannomas is an increasingly specialized area in which major advances have been seen over recent years. The effect of these advances on the referral patterns to a centre specializing in such surgery is reviewed. The proportion of referrals with a known diagnosis has increased substantially, allowing the specialist centre to focus on appropriate management rather than diagnosis. The vast majority of vestibular schwannomas are referred by otolaryngologists. The caseload referred by neurologists or neurosurgeons have different presenting symptoms. The incidence of vestibular schwannoma in the Cambridge district is found to be 1 per 50,000 population per year. This is a higher incidence than that recorded in other studies. This may be due to a tight diagnostic strategy and the high level of clinical awareness of the local general practitioners. PMID- 7788942 TI - General primer-mediated polymerase chain reaction for simultaneous detection and typing of human papillomavirus DNA in laryngeal squamous cell carcinomas. AB - The aim of this study was to investigate the prevalence of different human papillomavirus (HPV) types in laryngeal squamous cell carcinomas using general primer-mediated polymerase chain reaction (PCR). Tumour sections from 42 patients with laryngeal carcinomas were investigated. For HPV DNA amplification, consensus primers were used which were directed to the L1 coding region of the HPV genome. Analysis of the PCR products was done using 2% agarose gel electrophoresis followed by restriction enzyme analysis to identify different HPV types. Amplification of the human TGF-beta 1 DNA was successfully performed in 36/42 (85.7%) of samples confirming the presence of sufficient DNA for viral amplification. HPV DNA was detected in 8/36 (22.2%) of the tumours examined (three HPV-6, two HPV-16, one HPV-11, two unknown HPV types). HPV DNA was not detected in any of the non-neoplastic laryngeal mucosa which was used as control (n = 15). Fifty per cent of women had HPV-positive tumours compared with 8% of men (chi2 = 5.8, P < 0.05). Our data indicate that while the overall prevalence of HPV in laryngeal carcinomas is fairly high (22.2%), the frequency of high-risk types (HPV-16 & HPV-18) is low (5.5%). HPV probably acts as a promoter in the multistep process of carcinogenesis in squamous mucosal cells of the larynx. PMID- 7788943 TI - Mastoidectomy audit: results of the Royal College of surgeons of England comparative audit of ENT surgery. AB - This paper presents the results of a national comparative audit of mastoid surgery, retrospectively analysing 611 operations by 55 consultants. Confidentiality for both patient and surgeon was assured. For cholesteatoma 80% of mastoidectomies performed were open cavity procedures and for other middle ear disease 58% used an intact canal wall technique. Thirty-two surgeons used only an open cavity mastoidectomy for cholesteatoma during the period of the audit. There was a statistically significantly greater number of wet ears with open cavities than with closed cavities, but the frequency of the operator did not correlate with the dry ear rate. Ten serious complications (facial palsy and dead ear) were recorded. All occurred in open cavity mastoidectomies. The post-operative hearing status was unknown in 40% of patients. PMID- 7788944 TI - Unstable angina: cost of conservative and invasive strategies using TIMI3 B as a model. AB - Obviously, conservative therapy would be less expensive than invasive therapy if patients were held in the conservative category and received only medical therapy along with exercise test with thallium. However, based on the TIMI 3 B outcomes, costs are similar (but not equal) even if one attempts a conservative strategy since a significant number of patients in the early conservative arm underwent angiography (64 patients) and PTCA (26 patients) or surgery (24 patients) and the number of days for rehospitalization was greater in the early conservative than in the early invasive group. I believe the TIMI 3 B study reflects the reality of clinical practice in 1995. It seems to me that either strategy is acceptable both from the medical and economic outcome standpoints. Given the model used here, I do not think that the early invasive strategy will ever be cheaper than the early conservative strategy unless all of the patients in the early conservative strategy who eventually are revascularized have CABG, and all of the patients in the early invasive strategy who are revascularized have PTCA. PMID- 7788945 TI - Sudden cardiac death in patients with hypertrophic cardiomyopathy: from bench to bedside with an emphasis on genetic markers. AB - Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes. Death often occurs suddenly in asymptomatic, apparently healthy individuals. Several clinical parameters as well as genetic factors have been characterized that can identify those HCM patients who are at high risk for sudden cardiac death (SCD). The clinical parameters that have some predictive values for SCD in HCM patients are the following: a prior history of SCD, a family history of SCD, history of syncope, symptomatic ventricular tachycardia on Holter monitoring, inducible ventricular tachycardia during electrophysiologic studies, and myocardial ischemia in children with HCM. Recent identification of mutations in the beta myosin heavy chain gene and genotype-phenotype correlation in HCM patients have shown that the beta myosin heavy chain mutations are also prognosticators in HCM families. Several mutations such as Arg403Gln and Arg719Gln are associated with a high incidence of SCD, while Leu908Val mutation is associated with a benign course and a low incidence of SCD in HCM families. Additional genetic factors such as a polymorphism in angiotensin-converting enzyme I gene may also contribute to a high incidence of SCD in HCM families. Identification and characterization of HCM patients at high risk for SCD provide the opportunity to render prophylactic therapeutic interventions, such as implantation of defibrillators, in these individuals. PMID- 7788946 TI - Prognostic significance of right ventricular dysfunction in patients with acute inferior myocardial infarction and right ventricular involvement. AB - Little is known about the influence of right ventricular (RV) dysfunction on prognosis of patients with acute inferior myocardial infarction (IMI) and RV involvement. Therefore, 99 consecutive patients (mean age 56.6 +/- 3.4 years) with RV involvement during acute IMI were followed for a 12-month period to clarify the influence of acute RV dysfunction on short- and long-term survivals. Forty-one patients with IMI evolved with severe arterial hypotension due to RV dysfunction, while 58 patients had no hemodynamic impairment due to RV involvement. Basal hemodynamic data (mean +/- SD) for patients with RV dysfunction were blood pressure (BP) 92/59 +/- 22/20 mmHg, systemic vascular resistance (SVR) 2314 +/- 252 dynes.s.cm-5, and cardiac index (CI) 1.3 +/- 0.3 l/min/m2. Patients without RV dysfunction demonstrated BP 113/74 +/- 20/16 mmHg (p < or = 0.05), SVR 1324 +/- 354 dynes.s.cm-5 (p < or = 0.01), and CI 2.6 +/- 0.5 l/min/m2 (p < or = 0.05). Angiographic differences noted were that hemodynamically compromised patients showed lower RV ejection fractions (0.27 +/- 0.08) than patients without hemodynamic disturbance [0.41 +/- 0.11 (p < or = 0.05)]; however, left ventricular ejection fractions were 0.48 +/- 0.10 and 0.52 +/- 0.12, respectively. Short- and long-term mortality rates were assessed during the follow-up period. Patients with hemodynamic impairment due to RV infarction had a higher mortality rate for the first month and for 11 subsequent months post MI than patients without hemodynamic impairment, that is 24.4 vs. 6.9 and 14.6 (p or = 70% stenosis) in 14 patients. SECHO revealed stress-induced wall motion abnormalities in the distribution of seven of nine obstructed coronary vessels without angiographic collaterals, but in only one of seven vessels with collaterals (p < 0.05). Six of eight obstructed vessels not associated with a stress-induced wall motion abnormality had collaterals, whereas only one of eight obstructed vessels associated with a stress-induced wall motion abnormality had collaterals. We conclude that (1) angiographically demonstrated coronary collaterals can protect against the development of stress-induced wall motion abnormalities despite the presence of a high-grade coronary artery obstruction, and (2) the lack of a stress-induced wall motion abnormality on SECHO in the perfusion territory of an obstructed vessel may suggest the presence of adequate collateral perfusion. PMID- 7788948 TI - Effects of treatment with lovastatin and pravastatin on daytime cognitive performance. AB - The HMG-CoA reductase inhibitors lovastatin and pravastatin have both proven to be effective and well tolerated in the treatment of hypercholesterolemia. To evaluate whether lovastatin or pravastatin might affect daytime cognitive function, a double-blind, placebo-controlled, two-period, incomplete block, crossover study was performed in 36 patients (24 per treatment) with primary hypercholesterolemia. Patients received placebo, lovastatin (40 mg), or pravastatin (40 mg) for 4 weeks. Following a 1-week washout period, patients were crossed over to either lovastatin, pravastatin, or placebo for an additional 4 weeks. Mental performance tests (digit symbol substitution, choice reaction time, auditory vigilance, selective reminding word recall, finger tapping), visual analogue rating scales, and the Profile of Mood States were administered before test drug administration and after 2 and 4 weeks of each treatment. After 4 weeks, no statistically significant differences between treatments in changes from baseline were observed on any parameter with the exception of digit symbol substitution, for which lovastatin and pravastatin were both significantly better than placebo but did not differ from each other. Low-density lipoprotein cholesterol was reduced 38% by lovastatin and 30% by pravastatin. In summary, neither of these chemically distinct HMG-CoA reductase inhibitors impaired daytime cognitive performance after 4 weeks of treatment in patients with primary hypercholesterolemia. PMID- 7788949 TI - Transesophageal echocardiographically guided atrial transseptal catheterization in patients with normal-sized atria: incidence of complications. AB - The incidence of cardiac complications from atrial transseptal catheterization has never been quantified in patients with normal-sized atria. Series defining the complication rate are derived from diseased hearts with structural changes that may alter the complication rate of the procedure. The generation of a standardized incidence of perforation in a population of structurally normal atria has important implications. A total of 46 atrial transseptal catheterizations guided by transesophageal echocardiography (TEE) for radiofrequency ablation of left-sided accessory pathways was performed in 42 patients during a 3-year period (1990-1993). Clinical and echocardiographic data were analyzed, with special attention given to TEE reports pre- and post transseptal catheterization. Only one complication occurred in the 46 procedures (2.2%): a perforation of the left atrium that led to pericardial effusion and cardiac tamponade. In a small series of patients with normal sized atria, we have demonstrated that TEE-guided transseptal catheterization in a procedure with a low complication rate. PMID- 7788950 TI - Effect of precordial electrocardiographic electrode placement on ST-segment measurement during exercise. AB - Research protocols often utilize serial exercise testing to examine the efficacy of anti-ischemic therapies. These tests, however, are prone to multiple sources of bias. This investigation sought to determine the influence of varying precordial electrocardiographic (ECG) electrode placement on the detection of exercise-induced ST-segment shifts. Fifteen coronary artery disease patients with abnormal exercise tests were studied. Based on the previous exercise test, the precordial electrode position exhibiting the greatest ST-segment shift was selected as the reference electrode. Four additional electrodes were placed around this reference electrode and exercise testing was performed. ECG strips were recorded every minute. The time-to-onset and -offset of ischemic-type ST segment depression was recorded. ST-segment depression was recorded during exercise from the reference electrode in 12 of 15 patients. Ischemic-type ST depression was also recorded in each of these 12 patients with the surrounding electrodes; however, the time-to-onset detected by all four surrounding electrodes concurred in only 5 of 12 (42%) patients. The time-to-offset of the ST segment depression concurred in 9 of 12 (75%) patients. Serial ECGs recorded from similar but not exactly the same precordial ECG electrode position should yield similar results for the detection of ischemia, but time-to-onset or -offset of ischemia may differ by 60 s or more. Small changes in the time-to-onset and offset of ischemia should not be considered reliable indicators of anti-ischemia efficacy. PMID- 7788951 TI - Pathology of tricuspid valve stenosis and pure tricuspid regurgitation--Part III. AB - This three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part III, morphometric analysis of tricuspid valve annular circumference, leaflet area, and the product of annular circumference and leaflet area are shown to be useful in establishing etiology for the purely regurgitant tricuspid valves and in assessing the anatomic basis of pure tricuspid regurgitation in the presence of mitral stenosis. PMID- 7788952 TI - Pulmonary venous flow in constrictive pericarditis. AB - A 35-year-old white female patient presented with radiation-induced constrictive pericarditis. Intraoperative transesophageal echocardiography revealed a uniphasic diastolic flow pattern. This pulmonary flow pattern reverted to a normal biphasic systolic/diastolic profile immediately following radical pericardiectomy. This abnormal flow pattern was previously described as typical for restrictive cardiomyopathy. However, in this case it is most likely due to a marked decrease in left atrial compliance induced by the thick fibrous scar encasing the atrial. PMID- 7788954 TI - John Forbes. PMID- 7788953 TI - A case of cardiac sarcoidosis with remarkable atrophy of the left ventricular septum on two-dimensional echocardiography. AB - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology which mainly affects the lungs, skin, the lymphoreticular system, and the heart. We report a case of cardiac sarcoidosis in which a remarkably thin ventricular septum was demonstrated on two-dimensional echocardiography. PMID- 7788955 TI - Evaluation of acute haemodynamic response to high-dose naloxone in young hypertensive and normotensive humans. AB - Cardiac output is increased in many young subjects with mild essential hypertension. The purpose of these experiments was to determine if activation of endogenous endorphin systems contributes to this increase. We investigated the acute effects of the opioid antagonist, naloxone, on Doppler-derived stroke volume, cardiac output and systemic blood pressure in young hypertensive (n = 9) and normotensive (n = 9) subjects. On two separate sessions, naloxone (0.4 mg/kg) was administered intravenously over 10 min to resting subjects according to a random, double-blind study design. Stroke volume and cardiac output were determined before and 10 min after the injection; heart rate and blood pressure were measured at 1 min intervals before and up to 20 min after the injection. Baseline blood pressure, stroke volume, and cardiac output were higher in hypertensive than in normotensive subjects. Naloxone had no immediate effect on blood pressure, heart rate, stroke volume, or total peripheral resistance in either group. These results indicate that: (1) naloxone has no immediate haemodynamic effect in young hypertensive or normotensive subjects, and (2) the higher stroke volume and cardiac output of young subjects with mild essential hypertension cannot be attributed to activation of endogenous opioid systems that are antagonized by naloxone. PMID- 7788956 TI - Inhaled nitric oxide monitoring. AB - Recently, inhaled nitric oxide (NO) became clinically available for the treatment of persistent pulmonary hypertension of the newborn. Such use requires administration and continuous monitoring of a very low concentration of NO to prevent potential toxicity. Since limited data on the reliability of NO monitoring devices are available, we evaluated the performance of a chemiluminescent and electrochemical sensor NO analyzer in a patient ventilator circuit. RESULTS: The chemiluminescence analyzer readings were significantly altered by the oxygen concentration in the ventilator circuit. When the FiO2 was increased from 0.21 to 1, a 4.5% +/- 0.3 decrease in the NO readings was found (p < 0.01). Similarly, adding humidity to the circuit, reduced the NO readings by 4.8% +/- 0.9 (p < 0.01). The effect of gas pressure was proportional to its magnitude but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO readings increased by 3.94% +/- 0.05 (NO = 10 parts per million) and 3.97% +/- 0.02 (40 parts per million) (p < 0.01). The electrochemical sensor NO readings were directly proportional to the ventilator circuit pressure but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO reading was increased by 25.39% +/- 0.04 (NO = 40 parts per million) (p < 0.01) and 1.07% +/- 0.16 (NO = 10 parts per million) (p NS). The greatest difference with NO = 10 parts per million from baseline was found at a mean airway pressure of 6 cm H2O (6.67% +/- 0.23; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788957 TI - Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience. AB - We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD. PMID- 7788958 TI - Clarithromycin versus cefaclor in lower respiratory tract infections. The Canadian Bronchitis Study Group. AB - A randomized study was done to compare the efficacy of clarithromycin 250 mg or 500 mg b.i.d., vs. cefaclor 250 mg or 500 mg t.i.d. for 7-14 d in 197 evaluable patients with lower respiratory tract infection. Ninety-five patients received clarithromycin, 88 with acute bronchitis or exacerbation of chronic bronchitis, and 7 with pneumonia. One hundred and two patients received cefaclor, 86 with bronchitis and 16 with pneumonia. Ten patients (10.5%) in the clarithromycin group did not complete the trial, 5 (5.3%) because of adverse event, and 3 (3.2%) because of clinical failure. Similarly, 11 patients (10.8%) did not complete cefaclor, 2 (2%) because of adverse event, and 7 (6.9%) because of clinical failure. Clinical cure or improvement was observed in 90 (94.7%) of patients on clarithromycin vs. 92 (90.2%) on cefaclor, p = 0.66. Bacteriologic cure was seen in 26/36 patients (72.2%) on clarithromycin vs. 28/40 patients (70%) on cefaclor, p = 0.28. Clarithromycin is just as effective as cefaclor for lower respiratory tract infections and is well tolerated. PMID- 7788960 TI - Production of acyl-carnitines from the metabolism of [U-14C]3-methyl-2 oxopentanoate by rat liver and skeletal muscle mitochondria. AB - A sensitive method of continuous on-line radio-high performance liquid chromatography (HPLC) was used to detect the specific radio-labelled acyl carnitine esters derived from the oxidation of [U-14C]3-methyl-2-oxopentanoate by rat liver and muscle mitochondrial fractions. The recoveries of carnitine, acetyl carnitine, propionyl-carnitine, 2-methylbutyryl-carnitine, and hexanoyl-carnitine were 98.7% (+/- 5.4; SEM, n = 3), 91.4% (+/- 7.6), 89.4% (+/- 5.2), 84.6% (+/- 6.8), and 87.9% (+/- 7.8), respectively, from quenched mitochondrial incubations. This method demonstrated that rat liver and muscle mitochondria generate acetyl carnitine, propionyl-carnitine and 2-methylbutyryl-carnitine when incubated with [U-14C]3-methyl-2-oxopentanoate in the presence of carnitine. The production of acetyl-carnitine was almost similar in the 2 tissues. Muscle mitochondria produced higher amounts of propionyl-carnitine and 2-methylbutyryl-carnitine than liver mitochondria. These observations suggest a limited utilization of propionyl CoA by muscle mitochondria which, through a mechanism of feed-back inhibition, may have contributed to the accumulation of 2-methylbutyryl-CoA. This study provides further evidence for the importance of carnitine in the modulation of the mitochondrial [acyl-CoA/[CoA] pool. PMID- 7788959 TI - Does injectable gold retard radiologic evidence of joint damage in psoriatic arthritis? AB - The aim of this investigation has been to assess whether gold therapy prevents radiologic progression of psoriatic arthritis (PsA) over a period of 2 y. Eighteen patients (11 males, 7 females, mean age 42 y, DD 6.5 y) who were initiated on intramuscular gold during their attendance at the Psoriatic Arthritis Clinic were studied. For each gold-treated patient, 2 matched control patients, who had never had gold therapy, were identified from the PsA database. The control patients were similar to the patient population in gender, age, disease duration, number of actively inflamed joints, radiologic score and other medications used, and were followed in the clinic for at least 24 months. Actively-inflamed joint count decreased by > or = 40% in 9 of 18 gold-treated patients at 12 months. Seven patients continued gold for 24 months, while 11 discontinued gold for either lack of efficacy (4) or side effects (7). A comparison of the change in radiographic evidence of damage in the peripheral joints between the 18 gold-treated patients and the 36 controls revealed that there was no statistical difference in disease progression. These results suggest that gold therapy does not prevent the progression of damage in patients with psoriatic arthritis. PMID- 7788961 TI - The effect of interleukin-2 on suppressor T lymphocytes in autoimmune thyroid disease. AB - We have investigated the effects of interleukin-2 (IL-2) on the activation of suppressor T lymphocytes in autoimmune thyroid disease (AITD), with insulin dependent diabetes mellitus (IDDM) as an autoimmune disease control; this was accomplished by measuring the expression of major histocompatibility complex class II (HLA-DR), CD25 (IL-2 alpha receptor (R)), and IL-2 beta R expression on their surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 10 patients with Graves' disease (GD), 11 with Hashimoto's thyroiditis (HT), 9 with insulin-dependent diabetes mellitus (IDDM), and 10 normal persons (N), were cultured for 7 d in the presence or absence of IL-2 at a final concentration of 50 U/mL. CD8+ cells were isolated from cultured PBMC with immunomagnetic beads, and were stained with fluorescent-conjugated monoclonal antibodies (anti-CD11b, anti-IL-2 alpha R, anti-IL-2 beta R, and anti-HLA-DR); the activation of CD8+CD11b+ ("suppressor") T cells (Ts) by IL-2 was then analyzed on a flow cytometer. In the absence of IL-2, i.e., in the autologous mixed lymphocyte reaction (AMLR), Ts from patients with GD, HT, and IDDM showed significantly lower activation as compared to N when analyzed by HLA-DR expression, but were not significantly different when IL-2R expression was measured. We determined the Stimulation Index (SI) of the activation of T lymphocytes by IL-2 for comparison between N and patients. With stimulation of 50 U/mL of IL-2, SI of HLA-DR+ Ts was significantly (p < 0.05 to 0.01) lower in GD, HT, and IDDM as compared with N.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788963 TI - An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myoclonia: a probable ataxia telangiectasia variant. AB - We report a family of 4 siblings from a non-consanguineous marriage, presenting with an early onset recessive cerebellar ataxia and progressive distal limb wasting. Ocular or other telangiectasias were absent. There were neither frequent infections nor immunodeficiencies. The two youngest patients exhibited an incapacitating myoclonus which abated markedly after 20 years. Late onset diabetes was demonstrated in 3 patients. Hypogonadism was not a feature and there was a prolonged survival in the 4 patients. The oldest sibling died of a pancreatic adenocarcinoma. alpha-Fetoprotein was elevated with normal carcinoembryonic antigen values in three patients. Cytogenetic analysis and radioresistant DNA synthesis was compatible with the diagnosis of ataxia telagiectasia. This family probably represents a rare variant of ataxia telangiectasia. PMID- 7788962 TI - Higher in-hospital mortality in female patients following coronary artery bypass surgery: a population-based study. Provincial Adult Cardiac Care Network of Ontario. AB - This study examined the relationship between gender and in-hospital mortality using data from patients undergoing coronary artery bypass surgery (CABS) in the province of Ontario. All patients who underwent CABS between April 1, 1991 and March 31, 1992 at the 9 cardiac surgery institutions were included for study (n = 5,175). The unadjusted in-hospital mortality rate was 3.3% and was higher among females (5.3%) than males (2.8%). Using logistic regression analysis to adjust for several predictors of in-hospital mortality the odds ratio estimate (OR) for female sex was 1.55 and was statistically significant (95% confidence interval (CI) 1.09 to 2.20). Women experienced rates of in-hospital mortality that are 1.6 times greater than males following bypass surgery after case-mix adjustment for age, anatomical disease severity, anginal class, and comorbid conditions. Severe unstable angina had the greatest potential contribution to in-hospital mortality (OR = 7.51, 95% CI = 3.71-15.23) and was more prevalent in women, indicating that excess mortality may be due to delayed diagnosis in women. PMID- 7788965 TI - Anti-tumour therapy in paraneoplastic neurological disease. AB - Paraneoplastic neurological syndromes have attracted attention in recent years. Detection of auto-antibodies directed against CNS and PNS structures have suggested an autoimmune etiology. This review is based on reports from the past 10 years and summarizes the therapeutic results in 258 patients suffering from paraneoplastic neurological disease including paraneoplastic encephalomyelitis, sensory neuronopathy, cerebellar degeneration, motor neurone disease and stiff man syndrome. The results show that in some entities such as Lambert-Eaton syndrome successful treatment can be expected. In other syndromes such as subacute sensory neuronopathy or paraneoplastic cerebellar degeneration therapeutic success varies from 5 to 10%. PMID- 7788964 TI - Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice. AB - Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss. PMID- 7788966 TI - Immune modulation of paraneoplastic neurologic disorders. PMID- 7788967 TI - 'Lewy body disease': clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia. AB - One of the characteristic histological features of Parkinson's disease (PD), with or without dementia, is the presence of Lewy bodies (LBs) in the brainstem and neocortical and limbic structures. They are often accompanied by Alzheimer type pathology (ATP). In the present retrospective study the clinical features and post-mortem findings of 18 consecutive and unselected PD patients were compared, with special reference to the frequent but not exclusive association of LBs with ATP in Lewy body disease (LBD). LBD is the term applied to a particular pattern of neuronal degeneration associated with LBs. In this study of idiopathic PD patients ATP seems to be the major determinant of the cognitive decline in most patients. Cortical Lewy Bodies (CLBs) were present in all patients reviewed, whether or not dementia was present. It was not possible to distinguish a specific pattern in the cognitive or psychopathological symptoms of dementia that would differentiate LBD from Alzheimer's disease (AD). Although in most cases hippocampal CA2-3 ubiquitin immunoreactive neurites were observed, here again there was no correlation with the presence of dementia. PMID- 7788968 TI - An unusual case of central nervous system cryptococcosis. AB - Opportunistic infections of the central nervous system (CNS) in immunocompromised patients often represent a diagnostic and therapeutic challenge due to the variety of possible infectious agents causing CNS disease. We report the case of a severely immunocompromised 43-year-old woman presenting with headache, confusion, abnormal CSF findings (cell count 237/mm3 with 50% eosinophils and elevated protein), multiple contrast enhancing lesions on CT and MRI in the basal ganglia, and serologic findings compatible with latent or reactivated toxoplasmosis with high IgA and IgG antibody titers against Toxoplasma gondii in whom a final diagnosis of CNS cryptococcosis was made. This case illustrates the considerable difficulties in the differential diagnosis of opportunistic CNS infection in the immunocompromised host. We conclude from our report that (1) the diagnosis of toxoplasma encephalitis should not be based on serological findings but rather be proven by either PCR, mouse inoculation or brain biopsy, (2) CNS cryptococcosis can be associated with marked CSF eosinophilia and multiple cryptococcomas, and (3) cryptococcomas can persist on CT and MRI despite successful antifungal treatment. PMID- 7788969 TI - Positron emission tomography in spastic diplegia. AB - In this study, three patients with spastic diplegia were examined with magnetic resonance imaging (MRI) and positron emission tomography (PET), using the steady state technique with 15O. Two of them had untractable seizures and mental retardation. On MRI the cortical structures were normal; increased T2 signals in the periventricular white matter in the second patient were the main findings. PET scan showed in the two patients with a seizure disorder and mental retardation a large left cortical area of decreased regional blood flow and oxygen consumption during the interictal phase. The third patient without epileptic spells had a normal PET scan examination. It is concluded that the epileptic disorder in two of our cases is due to an additional cortical lesion, while the spastic diplegia is caused by subcortical white matter destruction. PMID- 7788971 TI - Seizures with negative phenomena. AB - Somatic inhibitory seizures and amnesic seizures are thought to occur rarely. We describe a patient with both types of seizures who initially presented with a clinical picture of transient ischemic attack. Neuroradiological investigations revealed a lesion probably a cavernoma located above the parietooccipital sulcus in the isthmus of cingulate gyrus. Anticonvulsant therapy eliminated both types of seizure. PMID- 7788970 TI - Desmoplastic low grade astrocytoma: a case report and review of literature. AB - A 7-year-old girl presented with focal seizures without symptoms of raised intracranial tension. Routine histological, immunocytochemical and ultrastructural methods revealed a desmoplastic low grade cerebral astrocytoma. Follow up for 2 years after biopsy did not show recruitment of neurological symptoms or signs. Biphasic tumours containing glial and mesenchymal elements have been described in the literature under various diagnostic headings. As the histologically benign variants of mixed glial and mesenchymal tumours appear to have a good prognosis, identification of these as separate entities seems imperative. With a review of literature we propose a pathological classification of mixed glial and mesenchymal tumours. PMID- 7788972 TI - Complete callosal disconnection after closed head injury. AB - We report a patient with complete callosal disconnection syndrome after severe closed head injury. MRI showed a complete destruction of the corpus callosum throughout its length. Although traumatic callosal lesions are a frequent finding in autopsy studies, as well as in some recent MRI studies, clinical signs of callosal disconnection are rarely observed after head injuries and a complete disconnection syndrome has not been reported yet. This case study and the review of other reported cases suggest that posttraumatic callosal disconnection is probably often overlooked. Our patient had also a severe memory disorder that might be partly related to the bilateral involvement of the fornix, as this structure is closely adjacent to the posterior corpus callosum, and was also shown by MRI to be very probably damaged. PMID- 7788973 TI - Ossifying fibroma of the occipital bone. AB - A case of occipital ossifying fibroma in a 13-year-old girl is presented. Ossifying fibroma is a rare, benign, primary bone tumour that occurs most commonly in the mandible. Cranial vault location is extremely rare. To our knowledge, our patient is the second case of occipital location reported. Total surgical excision is the treatment of choice. PMID- 7788974 TI - Racemose neurocysticercosis after chronic meningitis: effect of medical treatment. AB - A patient affected by racemous neurocysticercosis, occurring 5 years after the onset of chronic meningitis and followed by sequential MRI studies, is described. After ventriculo-peritoneal shunt, he was successfully treated with Praziquantel and Albendazole. This case may contribute to understand the natural history of the disease and stress the efficacy of medical versus surgical treatment of this lifethreatening disease. PMID- 7788975 TI - Post-heatstroke parkinsonism and cerebellar dysfunction. AB - A case is presented of a 45-year-old woman who developed parkinsonism, cerebellar dysfunction, aphasia and flaccid paralysis secondary to heat stroke. Magnetic resonance imaging revealed irregular patchy areas of increased signal intensity in the white matter of both cerebral hemispheres and the left striatum, remaining unchanged over a follow-up period of two years. Cerebellar atrophy, while not seen on initial examination, was present on the follow-up study done one year later and became more marked after two years. PMID- 7788976 TI - Unusual peripheral blood-count and CSF content during an outburst of Echo-30 meningitis. PMID- 7788977 TI - Paraneoplastic Neurological Disease, Recent Developments in Immune Diagnosis and Therapy. Proceedings of a symposium. Rotterdam, Netherlands, October 23, 1994. PMID- 7788978 TI - Clinical enigmas of paraneoplastic neurologic disorders. PMID- 7788979 TI - Immune diagnosis of paraneoplastic neurological disease. AB - A continuous stream of new information on clinical, pathological and immunological aspects of paraneoplastic neurological syndromes has been published in recent years. In this survey, we will discuss current opinions on the value of anti-neuronal antibody detection for establishing a diagnosis of one of the paraneoplastic syndromes of the central nervous system. PMID- 7788980 TI - Intradural tumors of the cauda equina: a single institution review of clinical characteristics. AB - A retrospective review of 106 cases of intradural tumors of the cauda equina are presented, subdivided into 5 groups according to their histological characteristics. For each group the clinical course and long-term postoperative results were analyzed: it emerged that differential diagnosis between neurinomas, meningiomas or non-tumoral lesions is not possible based on clinical findings alone and that neuroradiological diagnosis is more accurate when MRI is employed. Long-term prognosis was always favorable with the exception of the group of ependymomas. Nevertheless, early diagnosis in the latter group of tumors gives excellent results because prognosis is apparently directly correlated to the length of preoperative clinical history. PMID- 7788981 TI - Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 1. Mouse strains bearing different MHC molecules produce antibodies on immunization with recombinant Yo protein, but do not cause Purkinje cell loss. AB - Passive transfer of anti-Yo antibody from patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecological or breast carcinoma has not been successful in inducing an animal model. We used active immunization with recombinant Yo protein of four strains of mice bearing different MHC molecules: BALB/c (H-2d), C3H (H-2k), C57BL/6 (H-2b), SJL/J (H-2s). All the strains produced high anti-Yo antibody titer but none developed cerebellar ataxia or showed Purkinje cell loss. Spleen cells from the immunized mice also reacted with recombinant protein. Because C57BL/6(nu/nu) mice produce no anti-Yo antibody, mature helper T cells are required for its production. Results suggest that antibody production in peripheral blood alone is not sufficient for the development of PCD and that MHC class II molecules function in the activation of T cells to help B cells to help B cells produce antibodies. PMID- 7788982 TI - Characterization of chest masses by FDG positron emission tomography. AB - Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patlak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7788984 TI - Comparison of planar, SPECT, and 3-D synthetic reprojection images. A case study. AB - A case study is presented in which three types of images from a Ga-67 study are compared. The Ga-67 study was performed on a patient with fever of unknown origin (FUO). Planar and SPECT images were obtained. Planar data were presented as standard 2-D images on radiographic film. The SPECT data were used to generate two sets of images: standard 2-D multiple 'slice' images presented on radiographic film and a rotating 3-D synthetic reprojection displayed on a computer monitor. Compared to the planar and SPECT images, three sites of inflammation and the path of an oblique sinus tract were best seen in the 3-D synthetic reprojection. Recognition of anatomic structures and their spatial relationships was most readily apparent when viewing the 3-D synthetic reprojection, and this method of display facilitated the rapid recognition of abnormal findings. PMID- 7788983 TI - Prominent uptake of Tl-201 by duodenal leiomyosarcoma after exercise myocardial perfusion study. AB - Thallium-201 SPECT performed preoperatively for the evaluation of myocardial ischemia in a 72-year-old man with duodenal leiomyosarcoma demonstrated prominent focal uptake in the abdomen. Comparing a transaxial slice of SPECT through the abdominal uptake to the CT scan, the uptake was confirmed to be corresponding to the tumor. The tumor was delineated clearly, in good contrast to the surrounding normal intestine, which showed far less Tl-201 uptake than the tumor. In the delayed SPECT performed 3 hours after injection, although the intestinal activity became perceptible, the tumor still could be differentiated from the surrounding normal intestine. In this case, the exercise might be attributable to the initial low Tl-201 uptake by the normal intestine, which might otherwise have been an obstacle to Tl-201 scintigraphy for abdominal tumor detection. This case suggests the use of exercise for avoiding unfavorable intestinal activity, and the possibility of Tl-201 SPECT for abdominal tumor imaging. PMID- 7788985 TI - Eurysternum (extra-wide sternum)--a rarely recognized developmental anomaly. Scintigraphic appearances. AB - A rarely recognized extra-wide sternum was demonstrated by Tc-99m methylene diphosphonate bone scans in two adult patients. One patient was a 53-year-old man with prostate cancer who had no sternal symptoms or known sternal deformity. The second patient was a 41-year-old man with carcinoma of the lung whose extra-wide sternum was associated with a pectus excavatum deformity involving the lower half of the mesosternum (corpus sternum). A proper name for this developmental abnormality, "eurysternum" (eury-Greek word meaning broad; wide), is suggested. Two other patients, one with another type of wide sternum and another with a mesosternal foramen (fenestra sternii) deformity are also described. Related embryology and developmental anatomy of the sternum are reviewed. PMID- 7788986 TI - Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer. AB - The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase. PMID- 7788987 TI - Discordant findings between krypton-81m gas and Tc-99m labeled ultrafine aerosol lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis. AB - Technegas, a newly developed ultra-fine dry dispersion of Tc-99m labeled carbon with a particle size of approximately 5 nm to 20 nm, possesses the properties for lung ventilation imaging using SPECT. The authors observed a discrepancy between krypton-81m gas and technegas lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis who demonstrated heterogeneously decreased distribution of technegas without regions of high count density (focal hot spots) of tracer in their lungs in spite of the almost homogenous distribution of krypton-81m gas. This finding could be explained by the duration of radioactive gas inhalation. Technegas lung ventilation SPECT images reflected lung ventilation with tidal breathing. Conversely, Kr-81m gas lung ventilation SPECT images reflected not only lung ventilation, but also lung volumes. These two radioactive agents for lung ventilation SPECT show different findings. PMID- 7788990 TI - Tc-99m galactosyl-neoglycoalbumin hepatic scintigraphy in fulminant hepatic failure. AB - Tc-99m galactosyl-neoglycoalbumin (NGA) is a new liver imaging agent that specifically binds to a hepatocyte specific membrane receptor, the hepatic binding protein. Scintigraphy with Tc-99m NGA is a noninvasive method that provides functional images of the liver. This report deals with one case of fulminant hepatic failure in which hepatic scintigraphy with Tc-99m NGA predicted hepatic recovery before clinical and biochemical parameters, being a prognostic index in this patient. PMID- 7788988 TI - Efficacy of hepatobiliary scintigraphy in demonstrating cholangio-colic fistulae. Is formation of internal biliary fistula related to external leak closure? AB - The authors present four cases of internal biliary fistulae (IBF) identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an increased frequency of IBF formation in cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure. PMID- 7788989 TI - Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases. AB - The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment. PMID- 7788991 TI - Localization of infection in HIV antibody positive patients with fever. Comparison of the efficacy of Ga-67 citrate and radiolabeled human IgG. AB - Patients who are human immunodeficiency virus (HIV) antibody positive are at increased risk of life threatening infection. Scintigraphic imaging with Ga-67 citrate has been used to identify the presence and site of focal infection. However, focal accumulation of Ga-67 is not specific for infection. A retrospective study was performed to compare the accuracy of Ga-67 citrate and pooled human polyclonal immunoglobulin G (HIG) labeled with Tc-99m HIG and In-111 HIG in identifying infection in HIV antibody positive patients. Twenty-five studies were performed using Ga-67 and Tc-99m HIG were compared with a second group of 25 studies using In-111 HIG in HIV antibody positive patients presenting with fever, but without localizing symptoms or signs. In-111 HIG identified 20 of 22 sites of infection and also accumulated in 5 sites without infection (accuracy = 90%). This was significantly more accurate (X2, P < 0.05) than Ga-67 which identified 19 of 20 sites of infection, but accumulated in 18 sites without infection (accuracy = 74%) and Tc-99m HIG which identified infection in 11 of 20 sites, but accumulated in 8 sites without infection (accuracy = 77%). There was no significant difference between the accuracy of Ga-67 and Tc-99m HIG. From this preliminary study In-111 HIG would seem to be the best agent for identifying infection in HIV antibody positive patients with fever. PMID- 7788992 TI - An approach to cerebral vasodilatory capacity in unilateral and bilateral cerebrovascular diseases using radiolabeled human serum albumin. AB - The acute cerebrovascular response to acetazolamide was assessed using a blood pool agent and planar dynamic imaging to evaluate cerebral vasodilatory capacity. Ten normal subjects and 12 patients with unilateral or bilateral cerebrovascular disease were studied. After the injection of radiolabeled human serum albumin, dynamic imaging of the anterior view of the head was started. Ten minutes later, 1000 mg of acetazolamide was infused. The dilatation index (the percent increase in activity at the peak response) was obtained for each cerebral hemisphere. The mean dilatation index in normal subjects was 17.1 +/- 3.2% (N = 20). The value was significantly lower in patients with multiple infarcts (7.7 +/- 1.1%, N = 8, P < 0.001), and below the normal range in two involved hemispheres of five patients with unilateral occlusive carotid artery disease and in three hemispheres of three patients with moyamoya disease. It was suggested that this simple method may be useful in assessing cerebral vasodilatory capacity in both unilateral and bilateral diseases. PMID- 7788993 TI - Use of Tc-99m HMPAO brain SPECT to evaluate cerebral collateral circulation during Matas test. AB - Five patients with traumatic carotid-cavernous fistulae and two patients with internal carotid artery aneurysms inside the cavernous sinus are presented. A quantitative method was used for the evaluation of brain collateral circulation in the anterior and middle cerebral artery territories by using Tc-99m HMPAO SPECT before and during the Matas test. It affords a more reliable quantitative measurement of reduced activity than conventional carotid angiography during the Matas test. In this study, a reduction of radioactivity of less than 15% during the Matas test did not reveal any postoperative neurological deficit after a carotid artery trapping procedure. This noninvasive method seems to be useful to determine the appropriate surgical treatment. PMID- 7788994 TI - Tc-99m sestamibi uptake by malignant lymphoma and slow washout. AB - Tc-99m sestamibi has been used to detect primary brain tumors, lung tumors, and breast cancers. The authors report a patient who had superior vena cava (SVC) syndrome and underwent Tc-99m sestamibi and Tl-201 SPECT to differentiate the tumor from thrombus in the mediastinum because of an abnormal mass lesion on a contrast enhanced CT scan. An abnormal area of increased Tc-99m sestamibi uptake in the supra azygos area was demonstrated on early and delayed SPECT imaging. The washout of tumor uptake was slow. The removed tumor was confirmed to be malignant lymphoma. PMID- 7788995 TI - I-123 MIBG imaging of metastatic carcinoid tumor from the rectum. AB - I-131 MIBG, a specific radiopharmaceutical agent for scintigraphic imaging and treatment of pheochromocytoma and neuroblastoma may be useful for detection of apudomas. Scintigraphy with I-123 radiolabeled MIBG was performed in a patient with metastatic carcinoid tumor from the rectum. I-123 MIBG scintigraphic findings showed multiple areas of abnormal tumor uptake of hepatic and bone metastases from the rectal carcinoid. Bone scintigraphy demonstrated multiple metastatic lesions. Computed tomography revealed multiple solid tumors of the liver. This report describes accumulation of I-123 MIBG in the liver and bone metastases from the rectal carcinoid. Radioiodine MIBG scintigraphy may be useful for detecting metastatic lesions, for evaluating postoperative recurrence, and also for the treatment of the carcinoid tumor. PMID- 7788996 TI - Diagnostic value of Tc-99m (V) DMSA for chondrogenic tumors with positive Tc-99m HMDP uptake on bone scintigraphy. AB - Technetium-99m (V) DMSA scintigraphy was performed in 17 patients with 37 chondrogenic tumors (13 osteochondromas, 14 enchondromas, and 10 chondrosarcomas) that had previously shown uptake of Tc-99m HMDP. Technetium-99m (V) DMSA showed high uptake by all chrondrosarcomas, but low or no uptake always indicated benign chondrogenic tumors. Technetium-99m (V) DMSA scintigraphy may be superior to Tc 99m HMDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, and could also be useful for diagnosing the malignant transformation of chondrogenic tumors. PMID- 7788997 TI - Parathyroid adenoma localized in the lower neck in a patient with lingual thyroid demonstrated with Tl-201/Tc-99m pertechnetate scintigraphy. PMID- 7788998 TI - Scintigraphic detection of localized small bowel abnormality. PMID- 7788999 TI - A potential false-positive posttherapy radioiodine scan secondary to I-131 excretion in perspiration. PMID- 7789000 TI - Perfusion lung scanning with Tc-99m MAA in the assessment of Churg-Strauss syndrome. PMID- 7789001 TI - Fatty infiltration of the liver. An unusual presentation. PMID- 7789002 TI - Incidentally visualized hepatic hemangioma during dynamic renoscintigraphy. PMID- 7789003 TI - Hepatic angiosarcoma mimicking cavernous hemangioma. PMID- 7789004 TI - Bone scintigraphic appearances of massive bone allograft and local recurrence of sarcoma. PMID- 7789005 TI - Renal cell carcinoma extension into the inferior vena cava detected by Ga-67 citrate imaging. PMID- 7789006 TI - Tc-99m MIBI accumulation in remnant thymus. A cause of false-positive interpretation in parathyroid imaging. PMID- 7789007 TI - Papillary carcinoma arising in sublingual ectopic thyroid concentrating both Tc 99m pertechnetate and I-131. Diagnosis by fine needle aspiration cytology. PMID- 7789008 TI - Improving the diagnostic accuracy of Tl-201 imaging of intracranial tumors. PMID- 7789009 TI - Concepts of illness causality in a pediatric sample. Relationship to illness duration, frequency of hospitalization, and degree of life-threat. AB - In this study, we evaluated whether previous medical experience is associated with more sophisticated conceptions of illness causality among 64 children ages 4 to 16 years old. Although age and prorated IQ were found to be strongly related to children's illness causality concepts, duration of medical condition, total hospitalization days, and higher life-threat medical conditions were not associated with more sophisticated illness concepts in this pediatric sample. Using multiple regression analysis, age and IQ accounted for 59% of the variance in illness causality scores; contrary to expectations, medical experience variables (i.e., diagnosis, illness duration, hospitalizations) were not significant predictors of children's illness concepts. These findings highlight the need for pediatricians to guard against overestimating the illness concepts of children with prior medical experience. PMID- 7789010 TI - Children's conceptualization of illness: translating data into practice. PMID- 7789011 TI - Kawasaki syndrome masquerading as bacterial lymphadenitis. AB - We present two case reports of older children who initially presented with cervical lymphadenitis and who were eventually diagnosed and treated for Kawasaki syndrome (KS). Both children presented with unilateral cervical lymphadenopathy and fever and later developed additional clinical features of KS, including cardiac aneurysms in one of the patients. Of the five KS clinical criteria which accompany fever for 5 days, cervical lymphadenopathy of > or = 1.5 cm is the least commonly found. Both patients were treated as having bacterial adenitis prior to the diagnosis of KS. We hope to illustrate that in the case of atypical cervical lymphadenitis, KS should be carefully considered in the differential diagnosis. PMID- 7789012 TI - Marked heterogeneity in Niemann-Pick disease, type C. Clinical and ultrastructural findings. AB - Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder of unknown etiology. Diagnosis of NP-C is based on characteristic clinical findings and reduced fibroblast esterification of LDL derived cholesterol. We describe three patients who demonstrate the NP-C spectrum of clinical heterogeneity in age of onset, presenting signs, pattern of organ system involvement, and natural history. In addition, electron microscopic analysis of skin biopsy specimens from these patients revealed marked variability in the extent and cellular distribution of intralysosomal storage and was suggestive of the correct diagnosis in only one case. These cases demonstrate both the limitations of electron microscopy for diagnosis of NP-C and the marked clinical variability in patients with this disorder. Practical clinical guidelines for appropriate suspicion of NP-C are presented. PMID- 7789013 TI - Infective endocarditis in neonates. AB - We studied retrospectively the predisposing factors and signs of infective endocarditis (IE) in neonates and infants younger than 3 months of age, and we suggest diagnostic criteria. The charts of 16 infants less than 3 months of age, diagnosed with IE during a 5-year period, were reviewed for possible maternal and infant risk factors and for pathognomonic clinical and laboratory features. No apparent maternal risk factors were noted. Infant risk factors were congenital heart disease (4), patent ductus arteriosus (PDA) (5), and the use of central venous catheters (14). The main clinical findings were cardiac murmurs (12), petechiae (2), skin abscesses (7), arthritis (2), hepatomegaly (9), and splenomegaly (2). Echocardiography revealed a mass or vegetation in nine patients. Of the 27 microorganisms isolated from blood, the most common were staphylococci (15) and Candida sp. (6). Urine cultures were positive in six patients and cerebrospinal fluid cultures were positive in one. Other laboratory findings were not of diagnostic value. We conclude that the main risk factors for neonatal IE are central venous catheters and congenital heart disease, including PDA. The main causative microorganisms are staphylococci and Candida sp. The main investigations of diagnostic value are blood and urine cultures and echocardiography. We propose the diagnostic categories of definite, probable, and possible cases of neonatal IE, based primarily on clinical, blood culture, and echocardiographic data. PMID- 7789014 TI - Wolman disease and its treatment. PMID- 7789015 TI - Recombinant human erythropoietin (r-HuEPO) increases total bilirubin production in premature infants. PMID- 7789016 TI - Neonatal candidal meningitis in a full-term infant with congenital cutaneous candidiasis. PMID- 7789017 TI - Neonatal hemolytic-uremic syndrome. PMID- 7789018 TI - Serial changes of cystic air spaces in fibrosing alveolitis: a CT-pathological study. AB - In patients with cryptogenic fibrosing alveolitis (CFA), subpleural large cysts are sometimes seen within honeycombing on computed tomography (CT). These cysts may be interpreted as bullae and the coexistence of emphysema with CFA might be assumed. We evaluated whether cystic spaces in honeycombing become larger in patients with CFA on serial CT scans. CT scans were obtained in 16 patients with CFA, who had undergone two CT examinations (6 to 43 months, mean 25.1 months apart), were reviewed focusing on the changes in size of the cystic spaces in honeycombing. The mechanism of enlargement of cystic spaces was investigated using microscopic serial sections of autopsied specimens. In 15 of 16 patients, the cystic spaces in honeycombing were larger on the second examination. Histologically, stenosis of bronchioles and slit-like structures between cysts and bronchioles were detected in addition to alveolar septal dissolution and bronchiolectasis. Both the bronchiolar stenosis and the slit-like gaps have the potential to work as check-valves and increase the volume of cystic spaces. Therefore, in the evaluation of CFA, large cysts should be interpreted with caution to avoid misinterpretation of the cysts as bullae associated with emphysema. From the results of this correlative study, we suggest that a check valve effect is an important mechanism in the formation of large cysts in honeycomb lung. PMID- 7789019 TI - Delayed CT findings in acute renal infection. AB - The computed tomography (CT) findings in twelve patients with acute renal infection examined immediately and 3 h after i.v. contrast medium are reported. Three patients also had delayed scans at 6 h. Three main features were observed on the delayed scans: 1 a delayed nephrogram with streaky, wedge shaped or round high density areas. The areas of high density were at the same sites of the inhomogeneous areas of reduced density on the early scans; 2 focal contrast medium staining or a rim of increased density around abscesses; 3 focal areas of increased density at sites distant from the low density areas seen on the early scans. It is postulated that the delayed areas of increased density replace early areas of reduced density caused by ischemia due to vasospasm and/or compressing oedema of the vascular bed or by tubular obstruction. Delayed CT appears to be useful because it improves diagnostic confidence and gives a more exact evaluation of the extent of infection. PMID- 7789020 TI - Normal variation in the magnetic resonance imaging appearances of the sacroiliac joints: pitfalls in the diagnosis of sacroiliitis. AB - The purpose of this paper is to define the normal and variable appearances of the sacroiliac joints and adjacent subchondral marrow on unenhanced and enhanced Magnetic Resonance Imaging (MRI). Twenty subjects were imaged with spin-echo T1 weighted (T1), fast spin-echo T2-weighted (T2), T1-weighted with fat suppression (T1FS) and fast short tau inversion recovery (Fast STIR) sequences. Five of these subjects were imaged following intravenous Gd-DTPA administration, and the enhancement factor of the synovial compartment of the sacroiliac joint and subchondral marrow was calculated. The appearance of the cartilage of the synovial compartment on T1 and T2 images is of an intermediate signal bounded by signal void of bone cortex. On T1FS and Fast STIR images the cartilage has an intermediate to high signal. The marrow on T1, T2 and T1FS images has a homogeneous intermediate signal. T1FS images demonstrate the synovial compartment with greater clarity than T1 images. Cortical erosions and subchondral sclerosis were not demonstrated in our subjects, and partial volume artifact between the synovial and ligamentous compartments should not be interpreted as erosions. On Fast STIR images there is normally a region of high signal from the immediate subchondral marrow, which should not be interpreted as early sacroiliitis. Seven subjects demonstrated a patchy distribution of fat within the bone marrow, an appearance which alone does not indicate sacroiliitis. One subject had an accessory articular facet of the sacroiliac joint. The percentage maximal enhancement factor of the synovial compartment of the sacroiliac joint and adjacent subchondral marrow is 52% and 94% on T1FS images respectively. These figures redefine the normal maximal enhancement factors in this region of the body. PMID- 7789021 TI - Signal changes in the intervertebral discs on MRI of the thoracolumbar spine in ankylosing spondylitis. AB - Contrary to standard teaching in magnetic resonance imaging (MRI), recent reports have documented calcification appearing as areas of increased signal intensity (SI) on T1-weighted images. Intervertebral disc calcification is a frequent finding on radiographs in chronic ankylosing spondylitis (AS). This study was performed to investigate the appearance of variable degrees of disc calcification in MRI. Thirty-six patients with AS of variable duration underwent an MRI scan of the thoraco-lumbar spine and the MR appearances, particularly of the discs, were compared with plain radiographs. Increased SI of the discs on T1-weighted images were found in 17 of 36 patients, occurring over a range of disc levels, and correlating with disc calcification on the radiographs in 78% of cases. This group tended to be older and have a longer duration of disease than those with normal appearing discs. Four different patterns of increased signal within the discs termed Type A (marginal), Type B (annular), Type C (central) and Type D (solid) were identified. In those with less than six discs involved Type A was the most common pattern. In those with more than six discs involved Type D was the most common pattern, suggesting a progression of disc involvement with more advanced disease. Although these findings will not affect the management of the disease, they do highlight the recently described phenomenon of calcification appearing as increased SI on T1-weighted images, likely to be related to the surface area of the calcium crystal. This should lead to the consideration of calcium in the differential diagnosis of increased SI on T1-weighted images. End plate marrow changes were a relatively frequent finding in this study but did not correlate with the signal changes seen within the discs; in a number of cases they related to variable degrees of bony bridging. PMID- 7789023 TI - The application of ultrasound criteria for malignancy in differentiating tuberculous cervical adenitis from metastatic nasopharyngeal carcinoma. AB - Tuberculous adenitis and metastatic nodes from Nasopharyngeal carcinoma may have a similar clinical presentation. Clinical examination and laboratory tests alone are unable to differentiate the two. However, ultrasound is a useful initial investigation in differentiating these two conditions. We present ultrasound appearances in 33 patients with proven tuberculous cervical adenitis and 32 patients with proven metastatic nasopharyngeal carcinoma. The ultrasound features we found useful were the distribution of the nodes, cystic change, matting and surrounding soft tissue oedema. The size, shape and internal architecture of the nodes, previously described criteria in differentiating benign from malignant nodes, did not help. PMID- 7789022 TI - Can MRI predict the histopathological response in patients with osteosarcoma after the first cycle of chemotherapy? AB - The magnetic resonance (MR) changes after one cycle of chemotherapy were compared with the prechemotherapy studies in 39 patients with osteosarcoma, in order to identify MR changes which can be used to assess early response to chemotherapy. Measurements of total tumour volume, signal intensity, and tumour enhancement of the intra- and extraosseous tumour component were performed. Change in the amount of oedema was subjectively assessed. Changes observed were correlated with histopathological response. Changes in tumour volume and of the signal intensity of the extraosseous tumour component on T2-weighting were the only two parameters which correlated significantly (P < 0.05) with histopathological response. Increase of tumour volume is the most significant parameter and indicates poor response (sensitivity 89%, specificity 73%). Only one good responder showed increase of tumour volume. Decreased or stable tumour volume was observed in both good and poor responders. Increase of signal intensity was found exclusively in five poor responders (sensitivity 100%, specificity 23%). Decreased or stable signal intensity was observed in both good and poor responders. Changes in the amount of oedema and contrast enhancement could not predict response at an early stage. We conclude that increase of tumour volume and increase of T2 signal intensity of extraosseous tumour can be predictive for poor response. MR criteria are not helpful in the early identification of good responders. PMID- 7789024 TI - The prevalence and clinical significance of lymphadenopathy in primary biliary cirrhosis. AB - We present the results of a retrospective review of abdominal computed tomography, ultrasound, and magnetic resonance examinations of 12 patients with primary biliary cirrhosis undertaken to determine the prevalence and clinical significance of previously reported coexistent intra-abdominal lymphadenopathy in patients with this disorder. Lymphadenopathy, in the form of bulky periportal and retroperitoneal nodes, was identified in a single patient secondary to an occult metastatic adenocarcinoma. We conclude that coexistent intra-abdominal lymphadenopathy occurring in patients with primary biliary cirrhosis is uncommon. Although it may represent a benign component of the primary disease, it may equally be due to unsuspected coexistent occult malignancy. PMID- 7789025 TI - V/Q defects and deep venous thrombosis following total hip replacement. AB - Seventy-two patients undergoing elective total hip replacement were studied with bilateral venography, pre-operative and post-operative lung scans. Twelve belonged to a control group that received placebo injections and 60 patients to treatment groups that received low molecular weight heparin. The incidence of deep venous thrombosis was 11 (92%) of 12 patients in the control group and 18 (30%) of 60 patients in the treatment group (X2: P < 0.001). The incidence of pulmonary embolism (new unmatched perfusion defects) was five (42%) of the 12 patients in the control group and five (8.3%) of the 60 patients in the treatment groups (X2: P < 0.002). The incidence of pulmonary embolism (new unmatched perfusion defects) was eight (27.5%) of 29 patients with deep venous thrombosis and two (4.6%) of 43 without deep venous thrombosis (X2: P < 0.02). Of the ten patients who had pulmonary embolism according to this study's criteria (one or more new defect on perfusion, unmatched on the ventilation scan), eight would have been classified as high probability by the Biello criteria, and only five by the PIOPED criteria, if the pre-operative scans were not available. We conclude that having a pre-operative lung scan improves ability to interpret the postoperative lung scans in high risk patients. PMID- 7789026 TI - Demonstration of popliteal artery entrapment on leg muscle scintigraphy with 99mTc MIBI and single photon emission tomography. AB - Popliteal artery entrapment is difficult to diagnose even at surgery. Early diagnosis is important as the prognosis is better if detected before the onset of complications. There is no sensitive method for the evaluation of this condition. We describe three cases detected by a new technique using 99mTc methoxy isobutyl isonitrile (MIBI) with single photon emission tomography. The scintigraphic features of entrapment and the advantage of MIBI leg scintigraphy over other methods are discussed. PMID- 7789028 TI - Laryngeal chondroma: an unusual cause of upper airway obstruction. AB - Cartilaginous tumours of the larynx should be considered in the differential diagnosis of upper airway obstruction. We report two cases of chondroma of the thyroid cartilage and discuss the radiological findings in each case. PMID- 7789027 TI - Amyloid goitre: CT and MR findings. AB - Two cases of amyloid goitre presented as an enlarged thyroid mass with cystic components. Solid parts of the goitre showed high attenuation on computed tomography (CT) and moderate hypointensity on T1 and T2-weighted images. Fine needle aspiration was negative for amyloid, but pathological studies of surgical specimens demonstrated amyloid infiltration of the thyroid interstitium and regressive colloid cysts. In a patient at risk for systemic amyloidosis, thyroid enlargement with a cystic component suggests amyloid goitre. In this case, needle biopsies should be directed to solid areas of the mass because amyloid material may not be present in the cysts. PMID- 7789029 TI - Case report: multiple epidermoid cysts of the testes--the ultrasound appearances. AB - Epidermoid cysts are uncommon tumours of the testes representing approximately 1% of all testicular tumours. Their importance lies in the fact that they are completely benign and can be treated by local excision, thereby saving the patient an orchidectomy. We describe a case in which the patient had multiple epidermoid cysts involving both testes and faced possible bilateral orchidectomy. PMID- 7789031 TI - Case report: calcified stones in right-sided colonic diverticula stimulating gallstones. AB - Right-sided colonic diverticulosis, though unusual in the Western population, is common in the Orient. Calcified stones are rarely found within colonic diverticula. Standard textbooks of diagnostic radiology do not list calcified stones within caecal or ascending colonic diverticula as possible causes of calcification in the right hypochondrium or right iliac fossa. We present a patient with multiple laminated right-sided diverticular concretions mimicking gallstones. This possibility should be included in the differential diagnosis of gallstones or calcifications on the right side of the abdomen. PMID- 7789030 TI - Case report: symptomatic metastasis from a sacrococcygeal chordoma. AB - Chordoma is generally thought to be a locally invasive tumour of low metastatic potential. Review of the literature suggests that metastatic spread from chordoma is not an uncommon occurrence, but that the metastases are usually clinically silent. We present an unusual case where a metastasis from a sacrococcygeal chordoma produced a syndrome of lumbar root compression after resection of the primary lesion. PMID- 7789032 TI - Case report: a variant of the subclavian steal syndrome. Demonstration by duplex Doppler imaging. AB - The subclavian steal syndrome results from occlusion of the proximal subclavian or innominate artery which causes reversal of blood flow in the ipsilateral vertebral artery. We describe a case where a further occlusion of the ipsilateral common carotid artery (CCA) resulted in an intermittent reversal of flow in the ipsilateral external carotid artery (ECA), to siphon blood up the internal carotid artery (ICA) and down the ipsilateral vertebral artery. PMID- 7789033 TI - Acoustic attenuation in breast: a normal variant? PMID- 7789034 TI - Hodgkin's disease of the gastrointestinal tract. PMID- 7789035 TI - Corticosteroid prophylaxis for patients with increased risk of adverse reactions to intravascular contrast agents. PMID- 7789036 TI - Percutaneous antegrade ureteric stent insertion in malignant disease. PMID- 7789037 TI - The influence of trans fatty acids on health. PMID- 7789038 TI - The influence of trans fatty acids on health: a report from the Danish Nutrition Council. AB - Trans fatty acids constitute 0-30% of the fat in Danish margarines, most in industry and bakery margarines and usually less in table margarine. The trans fatty acids make margarines more solid at room temperature and therefore provide an economical storage advantage. In British and U.S. reports from 1984-1989, the trans fatty acids were more or less acquitted of unhealthy effects. During the last 5-6 years, however, a series of new studies has been published regarding both the connection between the consumption of trans fatty acids and the occurrence of coronary heart disease and the impact on the lipoprotein level in plasma. Studies suggest that the consumption of trans fatty acids from margarine is equally, or perhaps more, responsible for the development of arteriosclerosis than saturated fatty acids. In addition, it is now clear that both the fetus and the breast-fed baby are exposed to trans fatty acids in relation to the mother's consumption. A couple of recent studies suggest a possible restrictive influence of the trans fatty acids on the weight of the fetus. The average consumption of trans fatty acids from margarine in Denmark in 1991 was approximately 2.5 g/day per person. For about 150,000 adult Danes, the consumption is assumed to be more than 5 g/day per person. On this basis, the Danish Nutrition Council recommend that the consumption of trans fatty acids is reduced as much as possible. This can be done by reducing the fat content in food and by reducing the trans fatty acid content in all Danish margarine products to 5% or less. Thereafter, the group of adult Danes, including pregnant and breast-feeding women, with a large consumption of margarine and margarine-containing products, will on average only consume 2 g of vegetable trans fatty acids/day. This corresponds to the consumption in the low-risk groups in the above-mentioned epidemiological studies. In addition, the Danish Nutrition Council encourage the producers of margarines to make products that can be marketed as 'free of trans fatty acids'. PMID- 7789039 TI - Chemokines and human infection. PMID- 7789040 TI - Combined intestinal trefoil factor and epidermal growth factor is prophylactic against indomethacin-induced gastric damage in the rat. AB - 1. The availability of recombinant epidermal growth factor provides a potentially exciting development for the treatment of gastrointestinal ulceration. However, because of its potent mitogenic activity, there is a need for strategies which reduce the dose required. Intestinal trefoil factor stimulates mucosal healing without increasing proliferation. Studies were undertaken to examine the biological effects of rat intestinal trefoil factor and/or human epidermal growth factor upon gastrointestinal epithelial cell functions pertinent to mucosal protection, using two wounding models. 2. The study of epithelial restitution in vitro demonstrated a marked synergistic effect on the rate of migration of the wound edge when intestinal trefoil factor was used in combination with epidermal growth factor. There was no increased cellular proliferation due to the addition of intestinal trefoil factor to the cells when given alone, or to the stimulatory effect of cells treated with epidermal growth factor. In the rat model of gastric ulceration, the presence of both epidermal growth factor and intestinal trefoil factor protected against the development of indomethacin-induced gastric lesions. 3. We conclude that combination therapy of epidermal growth factor with intestinal trefoil factor could provide a more potent, safer approach to the treatment of human gastrointestinal ulceration. PMID- 7789041 TI - Metabolic acidosis is a potent stimulus for cellular inorganic phosphate generation in uraemia. AB - 1. During metabolic acidosis, significant fluxes of inorganic phosphate (Pi) may occur from cellular to extracellular fluid. In this study Pi was measured in erythrocytes of uraemic patients before and after haemodialysis and was related to their plasma pH (acidosis), plasma Pi (hyperphosphataemia) and cellular organic phosphate concentrations. 2. Before dialysis, the ratio of cellular to extracellular Pi concentration correlated inversely with plasma pH, increasing 2.5-fold as pH fell from 7.4 to 7.2. 3. An increase in cellular Pi similar to that seen in the patients was observed within 90 min of adding acid to normal erythrocytes in vitro. 4. The total Pi content of the cell suspension increased 25% on decreasing plasma pH from 7.4 to 7.2, largely as a result of generation of Pi from 2,3-bisphosphoglycerate in the cells. This was accompanied by net efflux of Pi into plasma. 5. In addition, the increase in the steady-state cellular Pi concentration on adding a constant extracellular Pi load was 50% greater at pH 7.2 than at 7.4, implying that alterations in the regulation of the transmembrane Pi gradient also contribute to the rise in cellular Pi observed at low pH. 6. At normal plasma Pi concentration (1 mM), glycolytic flux (lactate production) was inhibited by 20% when pH was lowered from 7.4 to 7.2. However, this inhibition was blocked when cellular Pi was increased by adding Pi to the plasma in vitro. 7. Metabolic acidosis is therefore a potent stimulus for Pi generation in erythrocytes, and this Pi may serve to stimulate glycolysis which is normally inhibited by low pH. PMID- 7789042 TI - Participation of endogenous atrial natriuretic peptide in the regulation of urinary protein excretion in experimental diabetic rats. AB - 1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats. 2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 +/- 5 (SE) versus 115 +/- 6 pg/ml, P < 0.01] and a higher glomerular filtration rate (3.3 +/- 0.1 versus 2.7 +/- 0.2 ml min-1 kg-1, P < 0.05). 3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats. 4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus. 5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (-61 +/- 14%, P < 0.02) and protein (-51 +/- 17%, P < 0.05). These changes were associated with a significant reduction in glomerular filtration rate (-32 +/- 11%, P < 0.05) and urinary cGMP excretion (-40 +/- 14%, P < 0.05). No significant effects of HS-42-1 on renal function were observed in control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789043 TI - Selective enhancement of alpha 2-adrenoceptor-mediated vasoconstriction in insulin-dependent diabetic patients with microalbuminuria. AB - 1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects. 2. To determine whether this is due to increased sensitivity at alpha 1 or alpha 2-adrenergic receptors, we compared vascular responses to the alpha 1 adrenergic agonist phenylephrine and the alpha 2-adrenergic agonist clonidine. 3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins. 4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16-2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin dependent diabetic patients. There were no significant differences between the dose-response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group. 5. Vasoconstriction mediated by alpha 2-adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy. PMID- 7789044 TI - Comparison of intraperitoneal and subcutaneous insulin administration on insulin sensitivity and serum lipids in type I diabetic patients on continuous ambulatory peritoneal dialysis treatment. AB - 1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a cross-over manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-(3)H]glucose as a tracer. 2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% +/- 0.46% and 9.52% +/- 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy. 3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery. 4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver. PMID- 7789045 TI - Investigation of the mechanism of beta 2-agonist-induced activation of the renin angiotensin system. AB - 1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789046 TI - Sympathoadrenal responses to bronchoconstriction in asthma: an invasive and kinetic study of plasma catecholamines. AB - 1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined. 2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in ls decreased by 38.7% +/- 4.1% (SE) and arterial PO2 by 3.0 +/- 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from < or = 1.18 nmol/l to > or = 1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 +/- 0.18 to 2.52 +/- 0.36 mmol min-1/m2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma. 3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction. 4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789047 TI - Effects of inhaled nebulized morphine on ventilation and breathlessness during exercise in healthy man. AB - 1. Nebulized inhaled morphine has been reported to increase exercise endurance in patients with chronic lung disease and to relieve dyspnoea in patients with malignant disease. Potential mechanisms include a central effect occurring after systemic drug absorption or a local action mediated by receptors in the lung. 2. The ventilatory effects of nebulized morphine (10 and 25 mg) were therefore compared with those of intravenous morphine (1.0 and 2.5 mg) and placebo in a double-blind study involving 12 young healthy males. Submaximal cycle ergometry with respiratory gas analysis was performed 15 min after drug administration and breathlessness assessed using a linear visual analogue scale. 3. Neither dose of inhaled morphine had statistically significant effects on spirometry, heart rate, ventilation, respiratory gases or breathlessness at any level of exercise. The slopes and intercepts of the lines relating ventilation to breathlessness were also unaffected. 4. Intravenous morphine 2.5 mg reduced breathlessness slightly at the highest equivalent workload [mean (least significant range) 33 mm (26-40 mm)] compared with placebo [41 mm (34-48 mm), P < 0.05] but had no other significant effects. 5. These results do not support the hypothesis that intrapulmonary opiate receptors modulate the sensation of breathlessness in healthy man. The possibility that inhaled morphine may affect breathlessness caused by other factors, such as disease, has not been excluded. PMID- 7789048 TI - Is voluntary control of breathing impaired in patients with chronic obstructive pulmonary disease? AB - 1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles. 2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (PaO2 = 53-71 mmHg), and one of these was hypercapnic (PaCO2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer. 3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol. 4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789049 TI - Relationship between plasma volume, carotid baroreceptor sensitivity and orthostatic tolerance. AB - 1. Studies were carried out on 43 otherwise healthy patients referred for investigation for attacks of syncope of unknown cause and on six healthy volunteers. 2. Plasma volume was determined by Evans Blue dye dilution and blood volume was estimated using haematocrit. Carotid baroreceptor sensitivity was determined from the changes in pulse interval in response to subatmospheric pressures applied to the neck overlying the carotid sinuses, and orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilt, followed by the addition of graded lower body suction. 3. Eight patients and one volunteer fainted during head-up tilt alone, 23 patients and two volunteers fainted during tilt with lower body suction at -20 mmHg and 12 patients and three volunteers either fainted during suction at -40 mmHg or tolerated the entire procedure. 4. Although plasma and blood volumes were higher in males than females, the values normalized for either body weight or for calculated lean body mass were not different between male and female patients and asymptomatic volunteers. The subjects showing the greatest resistance to syncope were found to have significantly larger plasma and blood volumes (P < 0.0001) and significantly smaller baroreceptor sensitivities (P < 0.0002) than those who fainted earlier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789050 TI - Demonstration of hypomethylation of proteins in the brain of pigs (but not in rats) associated with chronic vitamin B12 inactivation. AB - 1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both 'O' and 'N' methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain 'O' and 'N' methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man. PMID- 7789051 TI - n-Butyrate mediation of ganglioside expression of human and murine cancer cells demonstrates relative cell specificity. AB - 1. n-Butyrate, a short chain fatty acid produced by colonic fermentation, induces differentiation in human neoplastic cell lines, and reduces expression in vitro of a sialyltransferase that glycosylates N-linked glycoproteins in hepatoblastoma cells. Gangliosides are amphipathic, sialylated glycosphingolipids that undergo profound changes in many transformed cells and may protect neoplastic cells from host immune surveillance. Colonic mucosal cells are exposed to luminal short chain fatty acid concentrations of up to 80 mmol/l, and there is some evidence that short-chain fatty acids may alter ganglioside expression in colon cancer cells. 2. Because of the importance of gangliosides in cancer pathogenesis, we investigated the effects of n-butyrate on ganglioside expression of colonic (human and murine) and non-colonic cancer cells. 3. Three separate colon cancer cell lines (LS174T, T84 and MCA-38), when butyrate treated, demonstrated striking amplification of specific individual gangliosides. However, the total lipid-bound sialic acid content of gangliosides of butyrate-treated LS174T cells diminished. In contrast to earlier reports, n-butyrate did not mediate expression of all gangliosides and specifically did not mediate expression of GM3. This effect persisted even after removal of butyrate. 4. In contrast, exposure of extracolonic cells to butyrate, including cervical cancer (HeLa) and laryngeal cancer (HEp-2) cell lines in this study and hepatoblastoma cells (Hep G2) in our previous work, caused no detectable changes in ganglioside expression. 5. In conclusion, our results indicate a relative tissue specificity of butyrate mediated alterations in ganglioside expression that is not universal but is limited to specific gangliosides. PMID- 7789052 TI - Sensitivity versus specificity of phonoarthrography as an indicator for cartilage degeneration. AB - In an attempt to update the idea of recording knee sounds, 400 osteoarthritic (OA) knees, 100 knees from a young age group (18-31 years) and 100 knees from an age-matching group (45-60 years) were recorded by a computerized device using a special program that enabled the conversion of sounds--recorded in a fixed lapse of time--to waves which were then analysed in terms of frequency/second and average amplitude. Radiological grading was done for all groups in order to compare both parameters. Reproducibility of the recordings for each knee was confirmed statistically. Phonoarthrography was found to be 100% sensitive for radiological changes and for clinically felt crepitus, simultaneously diagnosing early OA in 32.5% of subjects with no radiological changes and in 7.5% of subjects with no clinically felt crepitus. From the work it can be deduced that computerized phonoarthrography can diagnose early cases of OA and is excellent for assessing and following up cases. It may be regarded as an indicator for cartilage degeneration. PMID- 7789053 TI - Medical, physical and psychological status related to early rheumatoid arthritis. AB - As part of an international European research project, a longitudinal study was started by the end of 1990 in the northern part of The Netherlands. The study concentrated on recently diagnosed RA patients (N = 292), i.e., incident cases up to four years. According to the duration of the disease, five groups of patients had been formed. The early influence of rheumatoid arthritis on medical parameters, on functional status, on physical condition and on psychological well being was evaluated. From the results, an overall statistically significant pattern related to the duration of the disease could not be distinguished. However, patients recently diagnosed did face activity restrictions, a decline in physical condition and social functioning. On medical parameters this deterioration is less profound. Furthermore, across and within the five patient groups, it seems that males and females respond differently to the influence of early RA. Based on cross-sectional data from the five onset cohorts, the present findings do not significantly suggest a steady worsening in medical, physical and psychological condition. PMID- 7789054 TI - The diagnosis value of beta 2-microglobulin and immunoglobulins in primary Sjogren's syndrome. AB - Salivary and serum concentrations of beta 2-microglobulin, salivary levels of the immunoglobulins, and salivary flow (as measured by a gravimetric method) were assessed in 34 patients and 11 controls. Of the 34 study patients, 16 had a primary form of Sjogren's syndrome (pSS) and 18 had sicca syndrome. The salivary and serum concentrations of beta 2-microglobulin and salivary levels of IgA and IgG were much higher in the patients with pSS than in controls or those with sicca syndrome (p < 0.001). Similarly, the salivary IgM levels of patients with pSS were higher (although at a lower degree of statistical significance) as compared to those of patients with sicca syndrome (p < 0.01) or controls (p < 0.05). No correlation was observed among the salivary flow and the salivary IgG and IgM levels, while there was a negative relationship (p < 0.01 with salivary IgA levels in all 45 patients considered as a whole. In 12 patients with pSS, the coefficient of correlation between the salivary gland biopsy focus score and the salivary (but not serum) concentration of beta 2-microglobulin was highly significant (p < 0.001). A similar relationship was observed with the IgG (p < 0.001) and IgM (p < 0.05) levels, but not IgA. In the diagnosis of pSS, the salivary IgA level demonstrates high sensitivity and low specificity. In contrast, serum and salivary concentrations of beta 2-microglobulin, salivary IgG, and to a lesser degree, salivary IgM have high specificity and positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789055 TI - Effect of oestrogen replacement on bone metabolism and cytokines in surgical menopause. AB - The effect of oestrogen replacement on bone metabolism and serum cytokine levels (IL1,IL6) was investigated in surgical menopause. The study included 40 female subjects; 10 healthy premenopausal women underwent total hysterectomy without oophorectomy. Thirty healthy premenopausal women underwent total hysterectomy with bilateral oophorectomy. They were randomly divided into 3 groups of 10 subjects. The first group received natural estradiol (0.05 mg/day) for 6 months; the second group received natural estradiol (0.05 mg/day) and medroxyprogesteron acetate (10 mg/day) for 6 months, the third group received no therapy. Calcium phosphorus metabolism, inflammatory indices, serum IL1 and IL6 levels were tested before and 6 months after surgery in all patients. A significant increase in serum alkaline phosphatase, urinary cross-links, serum PTH and IL1-IL6 was observed in the untreated women with total hysterectomy and oophorectomy. No significant variation in any of the parameters considered was observed in patients treated with oestrogen, in those treated with oestrogens and medroxyprogesteron nor in patients without oophorectomy. These results in human "in vivo" confirm that ovarian steroids play an important role in regulating the production of IL1 and IL6 which could regulate bone resorption. PMID- 7789056 TI - Left ventricular wall motion abnormalities in 80 patients with systemic sclerosis. AB - Segmental analysis of left ventricular wall motion was performed in 80 patients with systemic sclerosis by echocardiography. Half of the cases showed normal wall motion. Eighteen of the 57 patients with limited cutaneous systemic sclerosis (31.6%) exhibited hypokinetic wall motion abnormalities, while five of the 23 cases with diffuse cutaneous systemic sclerosis (21.7%) had similar findings. The three cases showing akinesis also belonged to the limited scleroderma subgroup. Our findings show that hypokinetic wall motion abnormalities can be detected in a remarkably high proportion of cases with limited cutaneous systemic sclerosis. PMID- 7789057 TI - Multidisciplinary approach to fibromyalgia. A pilot study. AB - The aim of the study was to instruct a group of fibromyalgia patients how to solve problems related to activities of daily life. Sixteen female fibromyalgia patients completed a ten week multidisciplinary program, consisting of a cognitive and an exercise part. After ten weeks a reduction in general pain intensity (p < 0.05) was found. At six months follow-up sensory (somatic) pain intensity was reduced compared to baseline recordings (p = 0.05). All patients had made adjustments to their everyday life after ten weeks. Eight patients reported that they regularly practised relaxation techniques, and seven patients had undertaken dietary changes. Thus, the study shows that adjustment of activities in daily living may reduce pain in patients with fibromyalgia. Controlled studies are needed in the future. PMID- 7789058 TI - Characterization of systemic lupus erythematosus in patients in U.A.E. AB - Twenty-eight SLE patients (Arabs and Asians) in the UAE were studied in this report. The F:M ratio was markedly high; 27:1 in the group as a whole and 21:1 among Arabs. Local patients (Emirians) developed the disease at an earlier age compared to their expatriate Arab compatriots. Arthropathy occurred in 86% and nephropathy in 43% of cases. Next in frequency were leucopenia, mucocutaneous manifestations and serositis. Apart from lupus headache, the other neuro psychiatric LE were uncommon or not encountered. Anti-cardiolipin syndrome, Sneddon's syndrome, shrunken lung syndrome, sicca complex, thyrotoxicosis and myasthenia gravis were also present in this small group of patients. Their presence reflects the marked heterogeneity displayed by the disease irrespective of the number of cases involved. An unusually high prevalence of anti ds (DNA) antibodies (92.5%) as compared to ANF (82.5%) was detected (P = NS). Anti-Sm antibody occurred in 30% of cases particularly in those patients with lymphadenopathy and fever. There was a relative paucity in the prevalence of anti RNP, Ro and La antibodies in this group. Differences with and similarities to previous reports concerning other populations are also presented. PMID- 7789059 TI - Risk factors for the development of acute disseminated intravascular coagulation in patients with systemic lupus erythematosus. AB - Since acute disseminated intravascular coagulation (DIC) often contributes to a fatal outcome in patients with systemic lupus erythematosus (SLE), prediction of its development is important to prevent the occurrence of such an event. To analyze the risk factor(s) contributing to the development of acute DIC in SLE, we carried out a retrospective study of a series of 129 SLE patients, eight of whom developed DIC during the course of this disease, to assess which of the easily assessable parameters, present at the time of first medical examination, were of predictive significance. The important individual variables, determined by univariate analysis, were male sex, leukopenia, and infection. These factors were placed in a multivariate logistic regression model, and only one factor, infection at first medical examination, was found to have predictive significance for the development of acute DIC in SLE patients. The prevention and control of infection in SLE patients might have implications for preventing the development of acute DIC. PMID- 7789060 TI - Long-term performance in vitro and in vivo of dual-energy X-ray absorptiometry. AB - Dual-energy X-ray absorptiometry (DXA) is actually considered as one of the most appropriate techniques for measuring bone mineral content (BMC) and bone mineral density (BMD). An anthropomorphic phantom and a 25-year-old girl were repeatedly measured, 160 times and 50 times respectively, over an 18-month period to investigate performance in vitro and in vivo of a commercial DXA equipment (HOLOGIC QDR 1000). DXA is a highly accurate technique, the BMC and BMD determinations only overestimated the exact value of the phantom by 0.20% and 0.51% respectively. In vivo long-term (18 months) reproducibility of BMD of the spine is characterized by an interassay coefficient of variation (CVt) of 0.8% while, for the different regions of interest of the hip, BMD CVt varies from 1.1% (total zone) to 5.3% (Ward's triangle). In the subject tested, BMD sensitivity for changes of 2.2% at the lumbar spine and 3% at the hip were recorded. PMID- 7789062 TI - Cogan's syndrome: a new possible complication of antiphospholipid antibodies? AB - A 55-year-old woman with a six-year history of Sjogren's syndrome (SS) and the positivity of IgG and IgM antiphospholipid antibodies (aPL) developed a sudden onset of sensorineural hearing loss associated with vertigo. This suggested the presence of an atypical Cogan's syndrome (CS), which might be a focal, neurological complication of aPL. PMID- 7789061 TI - Anticardiolipin antibodies in the polymyalgia rheumatica-temporal arteritis syndromes. AB - A series of seven patients with the polymyalgia rheumatica-temporal arteritis (PMR-TA) complex is presented, each of whom during the clinical course demonstrated the presence of anticardiolipin antibodies (ACLs). Presenting symptoms consisted of proximal myalgias and stiffness characteristic of PMR in five patients and of visual symptoms and headache suspicious for TA in two patients. Two of the five PMR patients later developed jaw claudication characteristic of TA. Six of the seven cases demonstrated clinical evidence of a vasculopathic process such as a cerebrovascular infarct or a vasculitic syndrome. Previous studies have suggested an association between ACLs and PMR-TA, and this series of patients appears to provide more supporting evidence. Even patients who only manifested PMR symptoms without suggestion of accompanying TA developed vascular complications. An increasing range of symptoms have been recognized in association with ACLs, and the vasculitic syndromes of PMR-TA should be included as a possible association. While this series together with previous studies may suggest that the presence of ACLs in patients with PMR-TA symptoms may serve as a marker for the development of vascular complications, larger longitudinal studies will be necessary in the future. PMID- 7789063 TI - A case of Werner's syndrome associated with systemic lupus erythematosus. AB - The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases. PMID- 7789064 TI - Campylobacter jejuni arthritis in secondary amyloidosis. AB - We describe a case of infectious arthritis caused by C. jejuni which developed after C. jejuni enteritis in a patient with rheumatoid arthritis and hypogammaglobulinaemia. Extraintestinal infections of this enteropathogen are rare, but in patients with hypogammaglobulinaemia C. jejuni bacteriaemia is relatively common. The present patient suffered from hypogammaglobulinaemia due to a nephrotic syndrome in secondary amyloidosis. C. jejuni infection must be considered in patients with hypogammaglobulinaemia and arthritis. PMID- 7789065 TI - Adult polyomyositis/dermatomyositis associated with acute myeloid leukemia. A case report. AB - Reports of PM/DM associated with haematologic disorders are rare. We describe a 62-year-old man suffering from PM/DM who developed acute myeloid leukemia. The possible paraneoplastic nature of PM/DM in this patient is discussed. PMID- 7789066 TI - Asplenism and systemic lupus erythematosus. AB - Although functional hyposplenism, secondary to Fc-receptor blockage by circulating immune complexes saturation, has been described in systemic lupus erythematosus (SLE), only few cases of complete asplenism have been reported. We observed a 60-year-old woman with congenital asplenism who presented with active SLE. The course and the clinical characteristics of such patients are reviewed and the relationship between the asplenic state and initiation and severity of SLE are discussed. These patients are at high risk for fatal pneumococcemia and pneumococcal vaccine is recommended even if long term results are still conflicting. PMID- 7789067 TI - Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature. AB - The cauda equina syndrome (CES) is an infrequently recognised and poorly understood complication of ankylosing spondylitis (AS). We report a case of CES with enlarged caudal sac and multiple posterior arachnoid diverticula eroding the laminae and spinous processes of the lumbosacral vertebrae in a patient with long standing AS. The diagnosis was established using computerised tomography (CT) and magnetic resonance imaging (MRI). PMID- 7789068 TI - Secretory component deficiency in Behcet's disease. PMID- 7789069 TI - Clinical variability and life expectancy in osteogenesis imperfecta. PMID- 7789071 TI - 15th European Workshop for Rheumatology Research. Erlanger/Bamberg, March 16-19, 1995. Abstracts. PMID- 7789070 TI - Rheumatological manifestations of lipoatrophic diabetes. PMID- 7789072 TI - [Role of polychemoembolization in the treatment of primary and secondary tumors of the liver]. AB - Unresectable primary hepatocellular carcinoma (HC) and liver metastases (LM) of abdominal tumors (AT) in progression after systemic chemotherapy (CT) have a poor prognosis and few therapeutic options. From 12/91 to 10/93 we treated 20 patients (PTS) 11 men and 9 women, with HC (10) and AT (10) with the following PCE: percutaneous placement of intraarterial hepatic catheter, superselective embolization with lipiodol (5 cc), infusion, mixed with lipiodol, of epirubicine 40 mg/m2, 5-fluorouracil 700 mg/m2, mitomycin-C 10 mg/m2 in 30'. After infusion, the arterial tree was embolized with Ivalon until an almost complete slowing of arterial blood-flow, every 5-6 weeks (W). After a median follow-up of 28 W a total of 35 courses had been administered to 20 PTS. Median (M) age was 69 years. M PS was 2. Okuda stage in HC PTS: 1 stage I, 9 stage II. in 10 HC PTS, positive for hepatitis B virus, CT and b-IFN had failed, while 10 AT PTS (5 colorectal, 2 gastric, 1 uterine, 1 larynx, 1 choledochus) had progressed, after, at least, 2 CT regimens, and had only LM. Median time from the diagnosis of LM in AT PTS was 32 W (12-68). TOXICITY: liver enzyme elevation and LDH elevation were 3 times baseline values, 4 PTS had fever for 6 days, 3 PTS had ileus for 3 days. No myelosuppression was observed. M alpha-fetoprotein value decreased from 468 ng/ml, to 56 ng/ml after PCE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789074 TI - [High resolution computerized tomography in cystic fibrosis. Clinico-radiologic correlations in 25 patients]. AB - Twenty five patients with a clinical and radiological diagnosis of cystic fibrosis underwent high resolution Computed Tomography (HRCT) with the aim to study pulmonary parenchymal localization of disease. Both patients with initial pulmonary alterations and patients in a more advanced phase of the disease were studied. HRCT proved an excellent method for detecting very early lesions such as bronchiolar ectasia and bronchiolar obstruction by mucous accumulation. Moreover, HRCT proved to be very useful in detecting centrolobular and panlobular parenchymal lesions, with diagnostic information on axial and peripheral interlobular connective tissue. HRCT provided a better spatial definition of bronchiectasia and subpleural air if compared to conventional radiology. It also allowed for correct diagnosis of pneumothorax and detection of pleural fibrosis as a result of iatrogenic complications. PMID- 7789073 TI - [Diphosphonates in the treatment of osteoporosis and in the prevention of associated fractures]. AB - Diphosphonates are capable to increase vertebral bone mineral mass in postmenopausal osteoporosis. Because the risk of fractures is related to the reduction of bone mass, the positive effect of diphosphonates most probably produced a decrease in fracture rate. At present these drugs represent a rational option for the treatment of postmenopausal osteoporosis. PMID- 7789075 TI - [Significance of cobalt in living organisms. Biochemical, clinical, and therapeutic considerations]. PMID- 7789076 TI - [Individual arterial pressure variability in newborn infants, adults, and the elderly]. AB - The complexity of the cardiovascular function is related to a wide interindividual variability (VA) that changes with age. The aim of our study was to investigate the spontaneous blood pressure (BP) VA in 3 groups of 20 healthy subjects (S) each, 10 M and 10 F: Group I newborns 24 hours old; Group II 30-40 yrs; Group III 70-80 yrs. Each S underwent BP monitoring in a comfortable condition for 15'. Our data show an increase, with age, of both the average systolic and diastolic BP, paralleled by a simultaneous decrease of their standard deviations. Furthermore, the three distributions show a reasonably gaussian behaviour (maximum absolute value of the skewness was 0.21). These results emphasize the age-dependent reduction in functional flexibility of the cardiovascular system. A major pool of subjects is required to confirm our preliminary data. PMID- 7789077 TI - Candida chorioretinitis in meningococcal meningitis. AB - A case of Candida chorioretinitis in a patient suffering from meningococcal meningitis, admitted to the Infectious Disease Department of Frosinone Hospital, Italy, is reported. Five days after the onset of meningitis during antibiotic and cortisone treatment the patient experienced oropharyngeal candidiasis, ocular pain and blurring of vision; two days later positive scotoma appeared. Ophthalmoscopic examination revealed probable Candida chorioretinitis. Treatment with intravenous fluconazole at high doses was employed with complete recovery of the right eye, while visual acuity of the left eye was 2/10. The use of long-term fluconazole at the doses reported, commonly employed in the treatment of systemic mycoses, improves prognosis. PMID- 7789078 TI - [Risk in vascular surgery]. PMID- 7789080 TI - [Cystic fibrosis of the pancreas. Historical notes, sweat test, and neonatal screening]. AB - Chronologic milestones in cystic fibrosis (CF) are reported. The value of the sweat test and the most recent advances on neonatal CF screening are described. PMID- 7789079 TI - [Toxicology of reproduction and development. Pregnancy and periods of risks from drugs]. AB - The authors discuss the possibilities of drug interference with the reproductive system and especially during various stages of pregnancy: from the sequence of neurochemical events that condition the release of pituitary gonadotrophines at the level of the central nervous system to late events that may occur during development. After listing the periods of risk, drug-induced changes in the conceptus are illustrated on the basis of data registered in the literature. In this context, it is stressed that the dysmorphogenic effect is limited to the period of differentiation and organogenesis whereas it is becoming more and more obvious that drugs may also have variable effects on other stages of pregnancy where frequently they have specific pharmacodynamic actions on the fetus. The knowledge of these effects may be useful in order to avoid untoward actions on pregnancy or on embryo, fetus, neonate or postnatal development, but may also create a basis for in utero drug treatments of fetal pathologies. PMID- 7789081 TI - [The use of colchicine in the treatment of alcoholic liver fibrosis in the elderly. Report of 80 cases]. AB - Having briefly analyzed the metabolism of ethanol in elderly subjects and the evidence of great resistance of the senile liver to alcohol-induced damage, the Author describes histological, clinical, biohumoral features of fibrosis and the necessary therapeutic measures. Eighty clinical cases of hepatic fibrosis are also illustrated, studied and observed during five years. PMID- 7789082 TI - [Lamotrigine: first experience in Italy]. AB - LTG, lamotrigine is a new antiepileptic agent chemically unrelated to any established drugs in use. The safety and the efficacy of LTG (564.5 +/- 74.4) mg/day was evaluated as add-on therapy (plus CBZ) in a placebo controlled study of 34 patients with refractory partial complex and/or partial secondary generalized seizures. The incidence of adverse effects of the drug is low and the unwanted effects are reversible. The long half-life and lack of effect on other AEDs will render LTG an easily dosable addiction to a patient's existing regimen. Reduction in the total number seizures was recorded in 61.4% of patients. We conclude that LTG is an effective AED for treatment of therapy-resistant partial seizure. PMID- 7789084 TI - [C0Q10 in the prevention and treatment of primary osteoporosis. Preliminary data]. AB - Preliminary data are reported of an as yet uncompleted clinical study aimed at evaluating the therapeutic efficacy of C0Q10 for primary osteoporosis. In spite of the small number of subjects treated (only 5) the results obtained are evidence of the efficacy of this agent which had never before been used in the therapy of osteoporosis. The possible mechanisms of action C0Q10 are discussed in the light of an original interpretation of the etiopathogenesis of this very complex bone disease. Details of the study will be reported once the trial has been completed. PMID- 7789083 TI - [Treatment of chronic obliterative arteriopathy of the legs in the second Fontaine's stage. Personal experience with a buflomedil-pentoxifylline defibrotide combination]. AB - The authors provide evidence for the efficacy of the buflomedil-pentoxifylline defibrotide combination for treatment of lower limb chronic obstructive arterial disease, Fontain stage II. Improvement of walking autonomy obtained with these agents ranged from 50 to 100% in 29 of 36 patients (relative frequency = 0.80). PMID- 7789085 TI - [Uremic encephalopathy and oligo-elements]. AB - The author reports the probable pathogenetic connexions between oligo-elements and uremic encephalopathy. Acquired data concerning this rare pathology of the CNS are reported as well as those of more doubtful scientific validity. The behavior of the neuro-psychic sphere and the symptomatology deriving from both deficit and excess of Al, As, Mg, Cr, Mn, Se, etc. are subject to special attention. The result of these changes is a complex of syndromes that are difficult to identify, also because uremia is beset by a large number of complications which more or less directly involve the central and peripheral nervous system. PMID- 7789086 TI - [A case of a patient with multiple primary neoplasms: ileal leiomyosarcoma and bronchial carcinoid]. AB - Small bowel leiomyosarcoma and lung carcinoid are uncommon neoplasms, and the association of these two neoplasms has never been reported in the literature. In the present article we report the case of a man who developed carcinoid of the lung three years after being operated for leiomyosarcoma of the small intestine. The short time elapsed between the two diagnoses adds further interest to this case. PMID- 7789087 TI - [For your well-being: a healthy diet and adequate physical exercise]. PMID- 7789088 TI - British Diabetic Association medical and scientific section spring meeting. Coventry, 30-31 March, 1995. Abstracts. PMID- 7789089 TI - Soar and the case for unified theories of cognition. AB - Despite the potential importance to cognitive psychology of unified theories no attempt has been made to assess concretely the methodological problems that such theorising produces. This paper addresses this issue of unified theorising, and in particular the arguments for unified theories put forward by Newell (1990). Close examination of these arguments reveals that Newell's approach does not adequately counter the difficulties which beset the grand theories of the 1930s, nor the problems of irrelevant specification which arise in modern computational psychological work. These difficulties do not prevent the development of unified theories, but they do pose serious problems, problems which it is argued can only be met by rigorous empirical testing together with extreme methodological sensitivity. The methodological concerns lead us to examine Soar, perhaps the most well-developed unified theory, from methodological, computational, and empirical perspectives. Our conclusions are that, whilst Soar represents an impressive body of research, its methodological foundations are insecure, it is ill specified as a computational/psychological theory, and under empirical testing it does not stand up to close scrutiny as a unified theory. The Soar research programme as it currently stands thus fails to meet the necessary methodological demands imposed by unified theorising. PMID- 7789090 TI - Phonological recoding and self-teaching: sine qua non of reading acquisition. AB - The self-teaching hypothesis proposes that phonological recoding functions as a self-teaching mechanism enabling the learner to independently acquire an autonomous orthographic lexicon. Successful decoding encounters with novel letter strings provide opportunities to learn word-specific print-to-meaning connections. Although it may not play a central role in skilled word recognition, phonological recoding, by virtue of its self-teaching function, is regarded as critical to successful reading acquisition. This paper elaborates the self teaching hypothesis proposed by Jorm and Share (1983), and reviews relevant evidence. Key features of phonological recoding include an item-based rather than stage-based role in development, the progressive "lexicalization" of the process of recoding, and the importance of phonological awareness and contextual information in resolving decoding ambiguity. Although phonological skills have been shown to be primary in reading acquisition, orthographic processing appears to be an important but secondary source of individual differences. This implies an asymmetrical pattern of dissociations in both developmental and acquired reading disorders. Strong relationships between word recognition, basic phonological processing abilities and phonemic awareness are also consistent with the self-teaching notion. Finally, it is noted that current models of word recognition (both PDP and dual-route) fail to address the quintessential problem of reading acquisition-independent generation of target pronunciations for novel orthographic strings. PMID- 7789091 TI - Development, characterization, and initial evaluations of S1. A new chromogenic cephalosporin for beta-lactamase detection. AB - A novel, chromogenic cephalosporin reagent (S1) for beta-lactamase testing was produced that shares physicochemical characteristics with nitrocefin (formerly 87/312). S1 and nitrocefin in a disk-testing format for beta-lactamase performed at 100% agreement for detecting enzyme-producing isolates of Bacteroides fragilis group, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Staphylococcus aureus, and selected Enterobacteriaceae. The time required to achieve an initial color change or a strong positive reaction was comparable for both chromogenic reagents for all organisms except the Gram-positive species. S1 reaction times were approximately 50% faster than nitrocefin for beta-lactamase positive enterococci and S. aureus. These results from the developmental studies and a commercially prepared disk lot indicate that S1 is a promising beta lactamase disk test reagent with the ability to detect all significant enzyme producing species strains, some significantly earlier than the nitrocefin disk method. PMID- 7789092 TI - Recovery of Coccidioides immitis from blood and abscess fluid using the BacT/alert system. AB - We report the recovery of Coccidioides immitis from the blood and abscess fluid of two separate patients by using two automated blood culture systems. In the first case, an aspirate from a neck abscess containing C. immitis spherules was serially diluted and inoculated into liquid media used by the BacT/Alert and the Bactec NR660 blood culture systems. BacT/Alert bottles inoculated with 10(5), 10(4), 10(3), 10(2), 10 and two spherules produced a positive signal at 19, 24, 35, 42, 57, and 62 h postinoculation, respectively. Bactec NR660 bottles containing > 10(2) shperules and 10 spherules produced a positive signal after approximately 72 and 96 h of incubation, respectively. In the second case, a blood specimen incubated in BacT/Alert blood culture both was signaled positive after 82 h of incubation. No organisms were detected by Gram stain of the broth, but C. immitis grew after blind subculture. Our observations demonstrate that these rapid blood culture systems are capable of supporting growth of C. immitis. To our knowledge, this report is the first to detect C. immitis by these blood culture systems. PMID- 7789094 TI - Susceptibility of ciprofloxacin-resistant staphylococci and enterococci to clinafloxacin. AB - Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis obtained from the Ann Arbor Veterans Affairs Medical Center within the last decade were tested for susceptibility to ciprofloxacin and clinafloxacin. For MRSA isolates, the minimum inhibitory concentrations (MICs) of ciprofloxacin were several fold higher than those noted with clinafloxacin. Prior to the introduction of the fluoroquinolones (1984-1985), all MRSA isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, virtually all MRSA isolates were resistant to ciprofloxacin and a 50-fold increase in the MIC50 and MIC90 for clinafloxacin was seen. In 1985-1986, most enterococcal isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, one-third of all enterococci were resistant to both ciprofloxacin and clinafloxacin. Fluoroquinolone resistance developed more quickly in enterococci that demonstrated high-level gentamicin resistance. Thus, cross-resistance between clinafloxacin and ciprofloxacin was seen; however, the lower MICs of clinafloxacin for MRSA may allow the use of this drug for some MRSA infections. PMID- 7789093 TI - Comparison of three commercially available monoclonal antibodies directed against pp65 antigen for cytomegalovirus antigenemia assay. AB - A total of 102 blood samples were used in a prospective parallel and blind study to evaluate three commercially available anti-pp65 monoclonal antibodies for cytomegalovirus antigenemia assay, at the dilutions recommended by their manufacturers. Cytomegalovirus was detected in 42 samples (41.2%), by either culture (32 samples; 76.2% of positive samples) or antigenemia (38 samples; 90.6%). Of the antigenemia-positive samples, 37 were detected by Monofluo kit CMV, which showed statistically significant differences when compared with the other reagents (Biosoft 1C3 and Clonab C10/C11), in either positivity rates (P < 0.004) or positive cell counts (P < 0.001). This reagent also gave better results in fluorescence quality than 1C3 and C10/C11. However, technical differences were not reflected in the clinical relevance of the antigenemia results. PMID- 7789095 TI - Multicenter in vitro comparative study of fluoroquinolones against 25,129 gram positive and gram-negative clinical isolates. AB - In vitro activities of fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin were evaluated against 25,129 fresh bacterial isolates from 51 US hospital or medical center laboratories, beginning in October of 1990. Susceptibility rates were > or = 85% against most species of Gram-negative bacteria. Notable exceptions were Pseudomonas, Acinetobacter, Xanthomonas, and Providencia. The study drugs displayed similar activity against most Gram-negative species. At least 90% of oxacillin-susceptible staphylococci were susceptible but, of oxacillin-resistant strains, only approximately 60% of Staphylococcus epidermidis and 25% of Staphylococcus aureus were susceptible to the quinolones tested. Staphylococcus saprophyticus strains were less susceptible to fleroxacin (42%) than to the other compounds (79%-97%). Ofloxacin and ciprofloxacin were more active against streptococci, and none of the compounds demonstrated appreciable activity against enterococci. Thus, the spectra of activity of fluoroquinolones illustrate that they remain effective agents for the treatment of many types of infections caused by Gram-negative pathogens. PMID- 7789096 TI - In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci. AB - The results of susceptibility testing of 48 phenotyped strains of glycopeptide antibiotic-resistant enterococci are reported. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined for 27 vanA, 17 vanB, and 4 vanC strains. Antibiotics exhibiting the greatest activity included novobiocin (MIC90 = 8 micrograms/ml and MBC90 = 32 micrograms/ml), ramoplanin (MIC90 = 2 micrograms/ml and MBC90 = 4 micrograms/ml), and the streptogramin RP59500 (MIC90 = 4 micrograms/ml and MBC90 = 32 micrograms/ml). These antibiotics warrant further investigation as potentially useful agents, either alone or in combination, for treating enterococcal infections. PMID- 7789098 TI - Comparison of one-day versus two-day incubation of urine cultures. AB - The value of incubating urine cultures for 1 versus 2 days was evaluated prospectively for 1526 consecutive specimens. A total of 507 cultures (33.2%) were positive after 1 day; 41 (2.7%) showed different results after 2 days. Only yeasts and corynebacteria were detected more often with longer incubation. Patient charts were available for review from 27 of 41 late positives; in only three instances (11.1%) was action taken by physicians based on these results. PMID- 7789097 TI - Cross-resistance analysis for DU-6859a, a new fluoroquinolone, compared to six structurally similar compounds (ciprofloxacin, clinafloxacin, fleroxacin, levofloxacin, ofloxacin, and sparfloxacin). AB - Emerging resistance to the current fluoroquinolones has encouraged synthesis of new compounds in this class. We have evaluated the activity of DU-6859a, a novel halogenated quinolone, against a panel of 300 bacteria, relative to the activity of ciprofloxacin, clinafloxacin, fleroxacin, levofloxacin, ofloxacin, and sparfloxacin. DU-6859a was the most active of the fluoroquinolones studied and retains potentially useful activity against 80% of isolates resistant (minimum inhibitory concentration, > or = 4 micrograms/ml) to ciprofloxacin. Continued clinical investigation of DU-6859a and similar new quinolones is urged. PMID- 7789099 TI - Interpretive errors using an automated system for the susceptibility testing of imipenem and aztreonam. PMID- 7789101 TI - Illness and cures in the Greek propitiatory inscriptions and dedications of Lydia and Phrygia. AB - The propitiatory inscriptions of Lydia and Phrygia (of the second and third centuries AD) manifest the belief that illness is a divine punishment for a sin (usually for a religious offence); cure can thus be achieved through expiation. Although scientific medicine was not unknown, the high costs of doctors, the belief in the omnipotence of gods, and the attribution of illness to divine intervention led the villagers to the local sanctuaries, where they received instructions by means of dreams and oracles. Some priests had medical experience, but they usually practised a 'religious healing' (incantations, purifications, sacrifices, the ritual transfer of the sin and the illness to animals). PMID- 7789100 TI - Variations in DNA subtype, antifungal susceptibility, and slime production among clinical isolates of Candida parapsilosis. AB - Candida parapsilosis is an important nosocomial pathogen that can proliferate in high concentrations of glucose and form biofilms on prosthetic materials. We investigated the genotypic diversity, slime production, and antifungal susceptibility among 60 isolates of C. parapsilosis from 44 patients and 10 patient care providers from five different medical centers. Molecular typing was performed using macrorestriction digest profiles with BssHII followed by pulsed field gel electrophoresis (REAG) and by electrophoretic karyotyping (EK). Slime production was evaluated by growing the organisms in Sabouraud broth with 8% glucose and examining the walls of the tubes for the presence of an adherent slime layer. Antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards proposed standard methods. Overall 28 different DNA types were identified by REAG and EK methods. MIC90 values ranged from 0.12 microgram/ml for itraconazole to 1.0 microgram/ml for fluconazole and amphotericin B. Sixty-five percent of the isolates produced slime: 37% were moderately to strongly positive, 28% were weakly positive, and 35% were negative. Overall, 83% of blood and catheter isolates were slime positive versus 53% of isolates from all other sites (P < 0.05). These data underscore the genetic diversity and susceptibility of C. parapsilosis to antifungal agents. Slime production may be important in enabling C. parapsilosis to cause catheter-related bloodstream infections. PMID- 7789102 TI - Ancient medicine in its socio-cultural context. Papers read at the congress. Leiden, 13-15 April 1992. PMID- 7789104 TI - The healing event in Graeco-Roman folk-medicine. AB - The inexplicit character of Graeco-Roman folk-medicine, together with the distorted and haphazard nature of our evidence, has led to easy denigration of its aims and methods. Analysis of the structure of the healing event, especially its spoken component, the charm, provides some insight into tacit beliefs about illness, and into the skills through which folk-practitioners won reputations for competence. Just as in school medicine, the basic aim is acquisition of the authority to intervene: correct diagnosis, drawing upon folk-categories, is followed by the reassertion of order through setting the present contingency into the context of a natural law or regularity, drawing upon the stock of shared knowledge. PMID- 7789103 TI - [Anatomia sacra. Religiously motivated interventions on human or animal bodies]. AB - Controlled surgery in the interior of human or animal bodies in classical antiquity was allowed only under certain circumstances. Bloody animal sacrifice and its rules for the interpretation of entrails as well as the rare examples of 'ritual anatomy' presented a religious framework for the opening of bodies. Greek mythology provided several examples of medical operations, for example, the Caesarean section, transplantations and plastic surgery. Great cultic significance was given to organ votives or reproductions of human inner organs which were offered in temples ex voto or with request for their curing. The anatomical knowledge transported along with these offerings represents a separate tradition different from the state of anatomical knowledge found in medical literature of the period. PMID- 7789105 TI - Tatian's 'rejection' of medicine in the second century. AB - The question why Tatian, often misrepresented as an opponent of medicine per se, chose to condemn only pharmacology, has never been directly raised. His conviction that pharmakeia was a demonic lure can only be explained in the context of both popular and medical attitudes toward drugs. The basic meaning of pharmaka ranges from sorcery to poison to medicinal drugs. Some people regarded them as categorically similar to substances used by brute beasts to cure themselves, a minority of physicians refused to administer them at all, whereas many revered them as virtually divine, 'hands of the gods'. Hence, in Tatian's view, they were spiritually dangerous for Christians. PMID- 7789106 TI - Athumia and philanthropia. Social reactions to plagues in late antiquity and early Byzantine society. AB - Thucydides' description of the plague at Athens stands as a paradigm that influenced eyewitness accounts throughout Greek and Byzantine history. Christian authors in Late Antiquity use his dark picture as heathen background against which they highlight Christian virtues of charity and mercy. The descriptions of the Justinianic plague of AD 542 rely on Thucydides not only stylistically but also in substance, as the early Byzantine society reacts like the people of ancient Athens rather than early Christian communities. PMID- 7789107 TI - [Intelligent man and medicine]. AB - In this article, three definitions of the ideal of the pepaideumenos (learned man) are examined in their mutual relations. In the pseudo-Platonic dialogue Amatores, the culture of the pepaideumenos is conceived as exhaustive as regards content, whereas it is attributed a merely 'formal' character in Plato's Charmides. However, on the theoretical level both solutions appear to be unsatisfactory. Aristotle's proposal is more convincing. He considers the pepaideumenos as the man who is able to assess the technicians' preparation adequately, since he knows the endoxa either with reference to knowledge as a whole or to individual technai. In all three cases, the example of the iatrike (medicine) is the means to test the validity of the proposed resolutions. PMID- 7789108 TI - [Non-Hippocratic references in Plato's dialogues]. AB - Plato's references to contemporary medicine are of a twofold nature. They initially concern Hippocratic medicine, first as an epistemological model in opposition with sophistic arguments, secondly as an instrument to define 'political art'. But in the later dialogues, Plato's references to medicine appear to evolve into a 'non-Hippocratic', magical type. This second type of reference-mostly in the Laws-is no longer metaphorical or analogical: it serves to determine the procedures that must be followed by the Law-Giver to establish a theocratic order. PMID- 7789109 TI - Medicine and the Lyceum. AB - Although Aristotle reveals a far higher degree of empirical observation than does Plato, he is fundamentally in agreement with him that the first principles of medicine should be drawn from philosophy. Like Plato, he adopts the four element theory, but prefers a system correlating 'elements' with binary combinations of opposites. It is argued that his biological and medical interests have influenced this general theory. It is also suggested that Diocles influenced considerably the development of anatomy and physiology within the Lyceum. Because of doctrinal affinities between Praxagoras and Diocles it has been maintained that the Lyceum exercised a dominant influence upon the subsequent history of Greek medicine; but caution must be enjoined. PMID- 7789110 TI - Aristotle on 'distinguished physicians' and on the medical significance of dreams. AB - This article studies the way in which Aristotle deals with the view-attributed by him to the 'distinguished physicians'-that dreams may be significant as clues for imminent diseases of the body of the dreamer. Aristotle is thinking of philosophically minded physicians (such as the author of De victu) who base their practice on principles derived from the study of nature in general and who take into account the constitution of the whole body. He accepts their view, but justifies it with his own theory of sleep and dreams; however, his attempt to incorporate the medical view into his own account brings him into conflict with his own presupposition that dreams are not actual perceptions, but experiences of the remnants of perceptions received during the waking state. PMID- 7789111 TI - [The epistemology of Erasistrate and Hellenistic technology]. AB - Erasistratus tried to build a coherent system of medicine founded on anatomical discoveries from which both physiology and pathology could be consistently derived. In this system, the so-called logoi theoreta are not merely theoretical constructions, but models (and/or metaphors) transferred to medicine from the two branches of contemporary Hellenistic technology, artillery and pneumatics. However, this system could not stand to the criticism of Empiricist medicine, both because of its oversimplification of pathology and therapy and because of its exceedingly heavy epistemological requirements. PMID- 7789112 TI - Alexander of Aphrodisias on medicine as a stochastic art. AB - Medical practice in antiquity was conspicuous for its failures, which seriously challenged medicine's status as an art. Ancient philosophers and doctors tried to explain how a whole group of arts including medicine, the so-called stochastic arts, was characterised by the fact that even the most competent exercise of the art could not guarantee a successful outcome. This paper focuses on Alexander of Aphrodisias' (second century AD) explanation and compares it to some other ancient views, in particular to Galen's. The central feature of Alexander's suggestion is a distinction between the end of an art and its function. In the case of medicine end and function do not coincide; for the end is to heal the patient, whereas the function consists solely in doing artfully what is possible to attain the end. PMID- 7789113 TI - Dialectic and science: Galen, Herophilus and Aristotle on phenomena. AB - This paper examines the nature of Galen's argument in the De placitis Hippocratis et Platonis, books 2-3, concerned with the location of the psychic functions within the body. To this question Galen applies a coherent set of methodological principles, integrating Aristotelian dialectic and scientific demonstration based on anatomical experiments. Galen disagrees with Aristotle in that he relegates the endoxa from the realm of dialectic to that of rhetoric. His attitude is marked by a distinctive emphasis on perceptible phenomena as the starting point for scientific inquiry. This and other features can be traced back to the Hellenistic scientist Herophilus. PMID- 7789114 TI - Science as text, science as history: Galen on metaphor. AB - This paper addresses three related questions: (1) What is Galen's theory of metaphor, and why is metaphor so important to him? (2) What is the place of metaphor in Galen's general theory of the language of science? (3) What is the relation of his theory of metaphor to his views on the historical dimension of language and to the historicity of science? PMID- 7789116 TI - Structure and style in the Hippocratic treatise Prorrheticon 2. AB - Bearing in mind both the capacity of man and his limits, the author of Prorrheticon 2 states his opposition to irrational prognoses and brings forward the semeia as the only basis for a correct prognostic. He does so by enhancing his statements by means of structure (ring-composition, psychological structure of recurrence) and style: in this field he uses several devices aimed to attract the reader's attention, putting together colloquial and high-level expressions. In this paper a similar stylistic technique is intended in order to illustrate the points of the Greek author. PMID- 7789115 TI - The embarrassment of imperfection: Galen's assessment of Hippocrates' linguistic merits. AB - In antiquity the 'higher' study of medicine shared with many other disciplines a pronounced philological character. Galen both exploited this 'philological paradigm' and underwent its influence. He exploited it in that it enabled him to invest the Corpus Hippocraticum with a dignity comparable to that of Homer only. But his philological instrumentarium, originally designed for the study of literary texts, also forced him to pose and answer certain questions that shed no light whatsoever on the informational content of Hippocrates' writings, questions about Hippocrates' language and style. Galen disentangles himself from the ensuing embarrassment by claiming that Hippocrates' style was ideal for the specific didactic genre he was involved in. This special style necessitates a reassessment of customary grammatical and rhetorical values: correctness recedes into the background, clarity and brevity become the predominant virtues of style. PMID- 7789117 TI - Notes on the syntax of Celsus. AB - This paper discusses five remarkable syntactic features of the language of Celsus' De medicina: praedicativa, the anaphoric pronoun is, instructive expressions, word order, and complex noun phrases. It is shown that these features should not be explained as 'vulgarisms', but as functional linguistic characteristics that are appropriate to the subject matter of the text and the requirements of scientific and technical exposition. PMID- 7789118 TI - [Technical medicine in ancient comedy]. AB - The texts of Greek comedy offer a panoramic vision of the evolution of medicine between the fifth and the third centuries. They provide an excellent way to understand the prejudices and the bases of technical medicine and its relationship with popular medicine. Comedy also shows us a vivid portrait of the physician and his position in Greek society. PMID- 7789119 TI - The longing for order: Oregon's medical advance directive for mental health treatment. PMID- 7789120 TI - Mental health case management: characteristics, job function, and occupational stress. AB - Although case management is an important component of treatment for persons with major mental illnesses, little is known about who works in case management, what functions are performed and how much occupational stress case managers experience. Mental health care managers (CM's) throughout the state of Oregon (N = 216) completed an inventory of case management functions and the job dissatisfaction and occupational stress scales of the Medical Personnel Stress Survey-Revised. The average expected tenure for a CM was 11 years, although one fifth expect to be a CM for four years or less. CM's spend 36% of their time performing administrative tasks, 20% in therapy, 17% with skills training, and 18% in case coordination tasks. CM level of education was associated with a different distribution of effort across case management functions. Greater job dissatisfaction was associated with specialized training, larger case load size and greater intention to leave the position. Consumer CM's demonstrated equivalent levels of job satisfaction as their non-consumer colleagues. The relevance of the project's findings for human resource management are discussed. PMID- 7789121 TI - The relationship of service individualization to client functioning in programs for severely mentally ill persons. AB - A measure of service individualization, derived from the goals in clients' treatment plans, was developed and used to evaluate this treatment process variable for 141 severely mentally ill persons served by three psychosocial rehabilitation programs. Relatively few of the 364 goals reviewed were highly individualized. Level of service individualization was inversely related to clients' functional skills, residential independence, level of education, and a primary diagnosis of an affective disorder, but positively related to a diagnosis of schizophrenia or another psychotic disorder. The goal individualization measure differentiated both between programs and among staff members, even after controlling for differences on client variables. PMID- 7789122 TI - Housing choice and community success for individuals with serious and persistent mental illness. AB - Consumer choice is a central principle of psychosocial rehabilitation and supported housing approaches. This study assessed level of housing choice and the relationship of choice to community success in supported housing demonstration projects in five states. Assessment of level of choice about housing revealed very limited housing options and a high degree of influence from service providers over housing choice. Despite few options, most respondents liked their housing option(s) and felt they had enough information to make a good housing decision. The relationship of choice to community success over time demonstrated that choice was positively related to housing satisfaction, residential stability, and psychological well-being. Discussion focuses on implications of the findings for mental health services and public policy. PMID- 7789123 TI - Innovative programming in a community service center. AB - A Community Center in a downtown urban area offers comprehensive services that provide continuity and choice to homeless and poor people. Emphasis is on outreach, through a Day Treatment Program for severely, persistently mentally ill homeless, a mobile outreach team, and neighborhood services, and/or employment, including a restaurant and Employment Reintegration Program. The Center is an example of how professionals, community and business leaders, and citizens can unite to assist clients and how programs can evolve from clients' requests and participation in services. The Center's programming can be followed in any community in this health care reform era. PMID- 7789124 TI - Living with chronic mental illness: understanding the role of work. AB - This paper is based upon an exploratory study designed to examine the role of work within the lives of those with severe, persistent mental illness (SPMI). In depth, open ended interviews were conducted with a small number of consumers (n = 10) who attend a clubhouse for those with SPMI where emphasis is placed upon preparation for work. Given that little is known about how work impinges upon or enriches the lives of consumers we asked consumers about their experience of mental illness and work throughout their life trajectories. This paper describes these work experiences, the effect of mental illness and treatment compliance upon their ability to work, and the relationship of work to stress. We found that in general some kind of meaningful activity was important to these consumers, but many had found work experiences to be stressful and were cautious about their subsequent abilities to sustain meaningful employment. We suggest that subsequent research needs to examine the nature of the work environment, and that work environments may be usefully distinguished in terms of level of expressed emotion. PMID- 7789125 TI - Around-the-clock mobile psychiatric crisis intervention: another effective alternative to psychiatric hospitalization. AB - This retrospective study evaluates the effect of the addition of a mobile psychiatrist to a 24-hour crisis intervention team, on the number of admissions, to the local state and private hospitals, of residents of the team's catchment area. During the Program period, the psychiatrist was available at the site of the crisis to provide immediate psychiatric treatment. The number of admissions to the hospitals during the Program period was then compared to those of the corresponding periods of the two previous years and of the year after, by means of a time series statistical analysis. When the on-site services of a psychiatrist were added to the mobile crisis intervention program a sharp decrease in state hospital admissions took place, without any increase in private hospital admissions. This decrease was followed by a definite rebound, after the on-site services of the psychiatrist were terminated, and throughout the following year. PMID- 7789126 TI - Some thoughts on: "around-the-clock mobile psychiatric crisis intervention". PMID- 7789127 TI - Use of neural networks as medical diagnosis expert systems. AB - A major bottleneck in building expert systems is the process of acquiring the required knowledge in the form of production rules. A novel class of neural networks is proposed to articulate the knowledge it learned from a set of examples. It provides an appealing solution to the problem of knowledge acquisition. After training, the knowledge embedded in the numerical weights of trained neural networks can be easily extracted and represented in the form of production rules. The approach is demonstrated by an example of a hypothesis regarding the pathophysiology of diabetes. PMID- 7789129 TI - Minimization of EOG artefacts from corrupted EEG signals using a neural network approach. AB - In this paper, we propose a neural network (NN) approach to the enhancement of EEG signals in the presence of EOG artefacts. We recast the EEG enhancement problem into the optimization framework by developing an appropriate cost function. The cost function is nothing but the energy in the enhanced EEG signal obtained through a nonlinear filter formulation, unlike the conventionally-used linear filter formulation. The minimization property of feedback-type neural networks is exploited to solve this problem. An analysis has been performed to characterize the stationary points of the suggested energy function. The hardware set-up of the developed neural network has also been derived. The optimum nonlinear filter coefficients obtained from this minimization algorithm are used to estimate the EOG artefact which is then subtracted from the corrupted EEG signal, sample by sample, to get the artefact minimized signal. The time plots as the LP spectrum show that the proposed method is very effective. Thus the power and efficacy of the NN approach have been exploited for the purpose of minimizing EOG artefacts from corrupted EEG signals. PMID- 7789128 TI - Connectionist networks in auditory system modeling. AB - Understanding how complex sounds, such as speech, are processed and eventually perceived in the brain is essential for building more effective speech processors. The echolocating bat provides an animal model for complex-sound processing of identified stimulus features at higher levels of the auditory pathway. In this paper, we present the use of connectionist models for modeling cortical neurons that play a key role in our auditory system model of a species of FM bat, Myotis lucifugus. The influence of network related parameters on modeling accuracy is presented, and the response of these models is explained in a behavioral context. PMID- 7789130 TI - Real-time multichannel abdominal fetal ECG monitor using digital signal coprocessor. AB - A real-time multichannel fetal ECG monitor based on a personal computer (PC) and a MOTOROLA DSP56001 Digital Signal CoProcessor (DSP) is introduced. The DSP board is plugged into the PC, which functions as a HOST computer. An analog 8 Leads Interface and Analog to Digital circuits module is connected to the DSP through a synchronous, optical-isolated communication channel. The fetal ECG detection is based on a cross-correlation technique. An averaged maternal ECG waveform is generated using a cross-correlation alignment procedure and a user-defined template. The fetal ECG signals present in the maternal waveform is suppressed during the averaging procedure, since both are uncorrelated. The average maternal ECG waveform is then subtracted from the abdominal real time signals, and maternal-free fetal ECGs signals are obtained, including fetal QRS complexes that coincide with maternal ones. Using the abdominal ECGs signals after subtraction, an averaged fetal waveform is generated. The maternal and the fetal heart rate are calculated during the process. The algorithm described above can be performed in real time on up to eight abdominal ECG traces by the DSP, and the desired results are passed to the HOST PC, to be stored and displayed. Electrodes positioning procedures for detecting the fetal QRS complexes with the best signal to noise ratio are not needed. Using the multichannel system, the user can select the best channel for fetal QRS detection, and accurate results for the heart rate signal are obtained. Averaged fetal waveforms are obtained from all the leads. PMID- 7789132 TI - Model analysis of time duration in a medication order entry system with attention to do-medication orders. AB - To investigate the relative time length needed for a medication computer order entry in comparison with the handwritten prescription system, we made a model, focusing our attention on the "do-medication order entry function." In the model analysis, we conducted a statistical analysis using the Nagoya University Hospital Information System. From the results and our model, if the time needed to make one (drug) item medication order entry is less than 1.9-3.0 times the time needed for handwriting one item prescription, computer order entry is faster on average. PMID- 7789131 TI - Improvements in accuracy and reproducibility of quantitative clotting factor assays by use of a novel approach for modeling reference curves. AB - A method for creating a reference model in the quantitative assay of specific clotting factor activities is described. This method incorporates the use of a piecewise function with two component polynomials. This function allows more accurate representation of the global coagulation reaction, a sequential activation of multiple serine protease enzymes and cofactors, leading to improvements over traditional methods in range, accuracy, precision and robustness in reported activity levels. Clotting factor assay results using this method are compared with traditional and other candidate methods. PMID- 7789134 TI - Computer acquisition, analysis and presentation of results from a Cobas Bio analyser. AB - Two computer programs for Macintosh computers have been developed in the LabVIEW programming language to perform data acquisition, analyses and presentation of results originating from a Cobas Bio analysing machine. One program is very flexible in its human interface, and is intended for research use. The program allows the results to be combined in a variety of ways, and allows the user to generate graphs to highlight the results. The other program is intended for routinely follow-up of analyses of proteases. It only allows the user to follow strict instructions, and only limited flexibility is built-in. PMID- 7789133 TI - PC program for assessing the relationship between rate of change and initial value. AB - A menu-driven PC program implementing Blomqvist's [J. Am. Stat. Assn. 72, 746 749, 1977] method for assessing the relationship between rate of change and initial value is described, illustrated and made available. It is shown that the naive approach to this problem--computing the correlation between the initial value and either the amount or rate of change--results in a negatively biased estimator. The extent of this bias can be dramatic and may lead investigators to conclude that a negative correlation is present when none exists; or that there is no correlation when in fact the correlation is positive. Blomqvist's (maximum likelihood) estimator avoids this bias, and is obtained by a transformation of the naive estimator. PMID- 7789135 TI - Design and analysis of multiarm clinical trials with survival endpoints. AB - The clinical trials literature has paid relatively little attention to the design and analysis of K-sample trials with survival endpoints where K is 3 or greater. Following the least-significant-difference approach proposed by Makuch and Simon [1], we derive sample size formulas by working with the logrank test and proportional hazards model directly. This approach ensures the type I error rate to be the nominal value when the global null hypothesis is true. For power considerations, planning the study based on the least favorable alternative is recommended. The resulting sample size requirements are presented in graphic form for K = 3 and 4. Assuming that there is a control group and considering only the alternative that the survival of the experimental treatments is at least as good as that of the control group, power investigations indicate that the proposed strategy has good power for detecting the difference between the control and the best treatment. The "overall power," defined as the chance of the global test and subsequent pairwise comparisons all being correct, is good when all treatments are similar to either the control or the best treatment. Overall power is poor when the hazards are more evenly spread out between the control and the best group because the sample size is inadequate to detect such differences. PMID- 7789136 TI - Stopping a clinical trial early because of toxicity: the Bayesian approach. PMID- 7789137 TI - Note on large, simple, widely representative trials. PMID- 7789138 TI - Requirements for controlled clinical trials of preoperative cardiovascular risk reduction. AB - Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed. PMID- 7789140 TI - Data quality assurance, monitoring, and reporting. AB - In conclusion, the quality assurance and monitoring program is an integral and continuing part of study operations. A system must be devised and implemented by the coordinating center investigators, with the endorsement of the study leadership and support of the field site and resource center personnel. Proactive mechanisms for promoting high-quality data acquisition and reporting must be implemented. Data quality monitoring must address the entire process by which the data are gathered, transmitted, stored, and analyzed. Data quality should be monitored continually, with summary reports prepared and distributed to the study leadership. Appropriate training and certification enhance data quality, and site visits allow data collection and storage processes to be observed directly. The quality assurance and monitoring system must be documented. It should be flexible enough so that new means of quality assurance or monitoring can be added when necessary during the course of the study. At the completion of the study, quality monitoring results should be summarized in a final report regarding the level of quality achieved by the study investigators and personnel. Finally, for a quality assurance and monitoring program to be successful, the coordinating center investigators and personnel must provide prompt feedback and suggestions for corrective action whenever a data quality problem is discovered. This need can be met only when the coordinating center staff understand data quality goals and are up to date with all phases of data management and reporting. Delays in initiating any stage of data management and quality monitoring may result in uncorrectable data problems. Thus, knowledgeable and efficient coordinating center personnel are essential to achieving good data quality studywide. PMID- 7789139 TI - Statistical design of the Child and Adolescent Trial for Cardiovascular Health (CATCH): implications of cluster randomization. AB - This paper describes some statistical considerations for the Child and Adolescent Trial for Cardiovascular Health (CATCH), a large-scale community health trial sponsored by the National Heart, Lung, and Blood Institute. The trial involves randomization of entire schools rather than individual students to the experimental arms. The paper discussed the implications of this form of randomization for the design and analysis of the trial. The power calculations and analysis plan for the trial are presented in detail. The handling of outmigrating and immigrating students is also discussed. PMID- 7789141 TI - Interim reports, participant closeout, and study archives. PMID- 7789142 TI - Approaches to data management. PMID- 7789143 TI - Functions and organization of coordinating centers for multicenter studies. PMID- 7789144 TI - Data collection and transcription. PMID- 7789145 TI - Mitral regurgitation: an overview. PMID- 7789146 TI - Molecular biology of Borna disease virus. PMID- 7789147 TI - Human infections with Borna disease virus and potential pathogenic implications. PMID- 7789148 TI - Natural and experimental Borna disease in animals. PMID- 7789149 TI - A Borna-like disease of ostriches in Israel. PMID- 7789150 TI - Borna disease--neuropathology and pathogenesis. AB - Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent. In the course of persistent infection of the rat, an elective, focal degeneration ensues that involves the dentate gyrus, retina, and, less frequently, the magnocellular part of the hippocampus. The cytopathic destruction of the dentate gyrus is the likely anatomical substrate of learning deficiencies and behavioral changes, prominent features of chronic infection. Later in infection, more diffuse and random degeneration of neurons can be found. In all species infected, viral antigens are produced in excess and fill all neuronal processes. Beside neurons, glial cells are infected as well. The agent spreads in the nervous system axonally and transsynaptically (transneuronally). The type of neurotransmitter receptors in the synapse and their interaction with viral proteins may modulate the spread of infection (Gosztonyi et al. 1994). Virus particles have not been visualized in the brain in any phase of the disease. During persistent infection of the rat, production of viral proteins has a phasic character. Some rats survive acute infection and develop an obesity syndrome. The anatomical basis of this syndrome is not fully clarified; inflammatory destruction of the infundibular region, vacuolar degeneration of the paraventricular nucleus of the hypothalamus and severe, progressive involution of the hippocampal formation most probably play an important role in the production of this neuroendocrine syndrome. In the acute disease, inflammatory reaction can severely aggravate virus-induced cytopathology, but cannot be the sole cause of the neurological disease, since infection with high passage virus can lead to a similarly severe disease in the absence of inflammatory changes. PMID- 7789152 TI - Behavioral disturbances and pharmacology of Borna disease. PMID- 7789153 TI - Clinical spectrum of measles. PMID- 7789151 TI - Immunopathogenesis of Borna disease. PMID- 7789154 TI - Measles virus gene expression in neural cells. PMID- 7789155 TI - Immune responses during measles virus infection. AB - The characteristic disease features of measles--fever and rash--are associated with the immune response to infection and are coincident with virus clearance. MV specific antibody and CD4 and CD8 T cell responses are generated and contribute to virus clearance and protection from reinfection. During this same phase of immune activation immunologic abnormalities are also apparent. There is a generalized suppression of cellular immune responses that may contribute to increased susceptibility to other infections. Autoimmune disease may appear in the form of acute disseminated encephalomyelitis. If virus-specific immune responses are inadequate infection may progress with pulmonary or CNS manifestations, but without a rash. The pathogenesis of the rare disease SSPE, that occurs many years after primary infection is not clear, but immune responses show increased antibody to measles and cellular immune responses similar to those seen after uncomplicated infection. PMID- 7789156 TI - The epidemiology of measles: thirty years of vaccination. AB - Measles is a highly infectious disease which has a major impact on child survival, particularly in developing countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about measles epidemiology and the best strategies for administering measles vaccines, as well as about the biological mechanisms of action of measles vaccines. However, it is clear that tremendous progress can be made in preventing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well tried methods of treating cases. Research in the coming decade may provide improved strategies and more effective vaccines for use in immunization programmes. PMID- 7789157 TI - Monkeys in measles research. PMID- 7789158 TI - Measles virus infections in rodents. PMID- 7789159 TI - The paradigms of measles vaccinology. PMID- 7789160 TI - Appendix: measles virus antigenome and protein consensus sequences. PMID- 7789161 TI - Structure, transcription, and replication of measles virus. PMID- 7789162 TI - Functional aspects of envelope-associated measles virus proteins. PMID- 7789163 TI - Measles virus strain variations. PMID- 7789164 TI - Measles virus-mononuclear cell interactions. PMID- 7789165 TI - Report and abstracts of the Fifth International Workshop on Human Chromosome 21 Mapping 1994. Tsukuba, Japan, November 9-11, 1994. PMID- 7789166 TI - Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridisation. AB - The three loci NRAS, NGFB, and CD2 map to human chromosome band 1p13. Using fluorescence in situ hybridisation (FISH) to simultaneously DAPI-banded metaphase chromosomes, we have further refined the localisation of these three genes to specific subbands. NRAS localises to subband 1p13.2 and CD2 and NGFB to 1p13.1. Also, with the use of multicolour FISH, we have determined the order and orientation of the three loci in relation to the centromere. The order is cen-CD2 NGFB-NRAS. PMID- 7789167 TI - Assignment of alpha 1-acid glycoprotein gene (ORM1) to swine chromosome region 1q210-->q212 by fluorescence in situ hybridization. AB - The porcine gene for alpha 1-acid glycoprotein (ORM1) was localized to chromosome region 1q210-->q212 by fluorescence in situ hybridization. From this result and published gene mapping data, it was concluded that the syntenic group comprised of ORM1, IFNA1, and GRP78 in the human genome is also conserved in the pig. PMID- 7789168 TI - Sequence identity locates CEBPD and FGFR1 to mapped human loci within proximal 8p. AB - The gene loci for human CEBPD (CCAAT enhancer binding protein, delta chain) and FGFR1 (fibroblast growth factor receptor) have been identified within two genetically mapped cosmids by sequence homology between rare cutter site regions and data base sequences for these loci. Cell hybrid and fluorescence in situ hybridization mapping places both of these loci within the chromosome region 8p11.2-->p11.1. PMID- 7789169 TI - Partial nucleotide sequence and chromosomal localization of a bovine zinc finger gene ZNF164. AB - A clone carrying an open reading frame coding for a novel zinc finger protein of the Kruppel family was isolated from a bovine genomic library and designated ZNF 164 (zinc finger protein 164). Partial sequencing revealed that it contained at least 13 zinc finger motifs preceded by a lysine-rich region of 60 amino acids. The ZNF164 protein shared approximately 60% similarity with several zinc finger proteins but did not appear to be orthologous with a previously identified gene. Using fluorescence in situ hybridization, the ZNF164 gene was mapped to bovine chromosome band 17q24. PMID- 7789170 TI - The human S-adenosylmethionine decarboxylase gene: nucleotide sequence of a pseudogene and chromosomal localization of the active gene (AMD1) and the pseudogene (AMD2). AB - S-adenosylmethionine decarboxylase (AdoMet-DC) is a key enzyme in polyamine biosynthesis. The human genome contains at least two loci for the AdoMetDC gene (AMD), one of which (AMD1) has previously been mapped to chromosome 6 and the other (AMD2) to the X chromosome. The locus on chromosome 6 is the transcriptionally active gene. We now report characterization of the AMD2 locus (GenBank Accession No. U02035) on the X chromosome, which contains sequences that cross-hybridize with human AdoMetDC cDNA. This DNA lacks all of the introns present in AMD1 and has numerous mutations in the protein-coding region. Its overall nucleotide sequence identity with AdoMetDC cDNA is about 90%. AMD2 is therefore a processed pseudogene, which, because of multiple mutations, cannot be translated to an active AdoMetDC enzyme, even if it were transcribed. Chromosomal loci for human AMD sequences were determined by in situ hybridization to metaphase chromosomes, with genomic DNAs from the active gene and the pseudogene loci as probes. AMD1 was localized to chromosome region 6q21-->q22 and AMD2 to band Xq28. PMID- 7789171 TI - Sequence of mouse Odf1 cDNA and its chromosomal localization: extension of the linkage group between human chromosome 8 and mouse chromosome 15. AB - The mouse cDNA encoding the major protein of the outer dense fibers in sperm tails was isolated by reverse transcription of testicular RNA and amplification with sequence-specific primers. Sequencing of a genomic clone obtained by inverse PCR yielded the 5' untranslated region. The transcription starting point was verified by primer extension. The putative proteins encoded by Odf1 in mouse and by ODF1 in rat and man are very similar. A total of 15 amino acids in the C terminal region were deleted in the mouse protein, compared with the rat protein. Through in situ hybridization to metaphase chromosomes, the Odf1 gene was localized to mouse chromosome 15 region B2-C. The chromosomal localization of the Odf1 gene extends the hitherto known linkage group consisting of MYC (Myc), PVT1 (Pvt1), GPT (Gpt), and TG (Tg) common to human chromosome 8 and mouse chromosome 15 in the proximal direction of both chromosomes. The linkage group now extends from band q24 to band q22 of human chromosome 8 and from region D2-E to region B2 C of mouse chromosome 15. PMID- 7789172 TI - Chromosome painting analysis of early oogenesis in human trisomy 18. AB - We have used chromosome 18-specific painting probes to analyze early stages of oogenesis in two human trisomy 18 fetuses. At leptotene, a diffuse, nonlinear chromosomal fluorescence was detected as one (27%), two (42%), or three (31%) signals in 534 cells. The variation in size of these signals implies the possibility of associations between homologs prior to zygotene. At pachytene, about 75% (339/453) of the cells had a trivalent configuration, and almost half of these cells exhibited almost complete triple synapses. Approximately 24% of the pachytene cells demonstrated a bivalent:univalent configuration, and 1% exhibited complete asynapsis. Our data imply that triple synapses may be a regular feature of meiosis involving multivalents. PMID- 7789173 TI - The human gonadotropin-releasing hormone receptor gene (GNRHR) maps to chromosome band 4q13. AB - A cDNA representing the high-affinity gonadotropin-releasing hormone (GnRH) receptor has been molecularly cloned from the human pituitary gland, a breast tumor cell line (MCF 7), and an ovarian tumor. The nucleotide sequence of this cDNA was determined, and its expression in various human tumors and tumor cell lines was demonstrated. In this study, we localized the gene encoding the GnRH receptor to human chromosome 4, using polymerase chain reaction (PCR) analysis of genomic DNA from human x hamster somatic cell hybrids. The gene was sublocalized to chromosome band 4q13 using fluorescence in situ hybridization with the GnRH receptor gene (GNRHR). PMID- 7789174 TI - Isolation and mapping of the human beta-signal sequence receptor gene (SSR2). AB - We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane. Northern blot analysis revealed its ubiquitous expression in all organs examined. We also localized the human beta-signal sequence receptor gene (SSR2) to chromosome bands 1q21-->q23 by fluorescence in situ hybridization. PMID- 7789175 TI - Localization of the human AHNAK/desmoyokin gene (AHNAK) to chromosome band 11q12 by somatic cell hybrid analysis and fluorescence in situ hybridization. AB - Using a panel of somatic cell hybrids, we have mapped the locus for the AHNAK/desmoyokin gene (AHNAK) to human chromosome 11. Fluorescence in situ hybridization experiments independently confirmed the chromosomal localization and refined it to band 11q12. PMID- 7789176 TI - Chromosomal assignment of the human deoxyribonuclease I gene, DNASE 1 (DNL1), to band 16p13.3 using the polymerase chain reaction. AB - To localize the human deoxyribonuclease I (DNase I) gene, DNASE1 (DNL1), we performed a polymerase chain reaction (PCR) using DNA extracted from a panel of cloned human x rodent hybrid cell lines carrying different human chromosomes and screened for the presence of the expected PCR products. Two different sets of oligonucleotide primers specific for human DNase I cDNA sequences were used to amplify unique fragments in the human DNase I gene. Based on this work, DNL1 could be assigned to human chromosome 16. Furthermore, regional localization of the gene to 16p13.3 was performed by PCR analysis of a high-resolution mouse x human somatic cell hybrid panel that contained defined portions of human chromosome 16. PMID- 7789177 TI - PCR amplification and physical localization of the genes for pig FSHB and LHB. AB - Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are members of the glycoprotein hormone family and play essential roles in gametogenesis and sexual development of mammals. Fragments of the porcine genes coding for the beta subunits of FSH and LH were amplified by PCR and used as probes for radioactive in situ hybridization in order to map these loci in the pig. Primers were chosen on the genomic DNA nucleotide sequences of FSHB and LHB as published in GenBank. Fragments of 1,127 bp (FSHB) and 1,239 bp (LHB) were cloned and verified by sequencing. FSHB was localized to pig chromosome bands 2p1.6-->p1.2 and LHB to pig chromosome band 6q2.1. The localization of LHB to the so-called halothane region of chromosome 6 could be expected from comparative mapping data. For FSHB, no conclusions can be drawn in this respect since, up to the present, too few genes are located on porcine chromosome 2. PMID- 7789178 TI - Hemizygosity at the insulin-like growth factor I receptor (IGF1R) locus and growth failure in the ring chromosome 15 syndrome. AB - The ring chromosome 15 syndrome is characterized by mild-to-severe growth failure. We evaluated the status of the insulin-like growth factor I receptor (IGF1R) gene, which had previously been assigned to band 15q26 in several patients with de novo ring 15 chromosomes, to investigate a possible correlation between disruption or loss of the IGF1R gene with the severe growth failure phenotype. The presence or absence of the IGF1R gene on the ring 15 chromosomes of five patients was ascertained by in situ hybridization and gene-dosage (Southern) blotting. The location of the breakpoints was determined by typing polymorphic markers from the distal end of the long arm of chromosome 15 in both the probands and their parents. Deletion mapping determined that all breakpoints were distal to D15S100 and that the IGF1R gene is located between D15S107 and D15S87. Three patients who had suffered severe growth failure in early childhood were hemizygous at the IGF1R locus, while one patient with borderline short stature had two copies of the IGF1R gene. The correlation between IGF1R gene dosage and growth retardation demonstrated here in our ring chromosome 15 patients suggests a possible role for heterozygous IGF1R gene mutations or deletions in other cases of unexplained growth failure. PMID- 7789179 TI - Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA. AB - We have isolated a novel human cDNA that is highly related to Xenopus transcription factor IIIA (TFIIIA). This clone contains an open reading frame of 1,269 nucleotides encoding 423 amino acids, including nine repeats of the Cys2His2-type of zinc-finger domain. A comparison of its sequence with Xenopus TFIIIA revealed 63% identity in nucleic acids and 58% identity in amino acids over a large portion of the gene and predicted peptide, indicating that the human homologue is likely to function as a transcription factor. The zinc-finger domains of the predicted protein also showed homology with those of human genes such as WT1, transcriptional repressor YY1, and MYC-associated zinc-finger protein (MAZ). Northern analysis showed expression in various tissues examined. The human TFIIIA gene (GTF3A) was localized to chromosome band 13q12.3-->q13.1 by fluorescent in situ hybridization (FISH). PMID- 7789180 TI - Comparative mapping of the immunoglobulin C epsilon 1 gene (IGHE) in five species of nonhuman primates by fluorescence in situ hybridization. AB - The orthologous immunoglobulin C epsilon 1 gene (IGHE) of the common chimpanzee, pygmy chimpanzee, orangutan, white-handed gibbon, and Japanese macaque was assigned to the human chromosome 14 homologue in each species and regionally mapped by fluorescence in situ hybridization to PTR15q32 (common chimpanzee), PPA15q32 (pygmy chimpanzee), PPY15q32 (orangutan), HLA17qter (white-handed gibbon), and MFU7q29 (Japanese macaque). The gene localized to the terminal region of the chromosome in each species, and so this probe provides a new telomeric DNA marker for nonhuman primates. PMID- 7789181 TI - Clarification of dubious karyotypes in Hodgkin's disease by simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). AB - Cytogenetic studies on Hodgkin's disease (HD) typically reveal very complex karyotypes with a variety of numerical and structural abnormalities. The confusing thing is that about 10% of cases contain relatively discrete chromosome aberrations, for example a simple trisomy or loss of one single chromosome. Whether these karyotypes really correspond to Hodgkin and Reed-Sternberg (HRS) cells is uncertain. They could, for example, represent early stages in the evolution of the karyotype of the pathognomonic HRS cells. On the other hand, they could be artificial events that occur during the cytogenetic procedure. In our experience, isolated loss of the Y chromosome is the most frequent finding of this type. This aberration is usually considered to be a preparation artifact. However, if one takes into account that in HD up to 50% of male cases with complex karyotypes also lack the Y chromosome, a possible relation to HRS cells must be considered. The technique of simultaneous fluorescence immunophenotyping and interphase cytogenetic analysis (referred to as FICTION) is a powerful tool for studying the nature of cytogenetically abnormal cells. With the FICTION technique we studied four cases of HD in which the chromosome analysis had shown only the loss of the Y chromosome. Our aim was to clarify whether these karyotypes corresponded to the CD30-positive HRS cells. In two cases we found that HRS cells actually lacked the Y chromosome. There was strong evidence, however, that the HRS cells additionally had other chromosome aberrations and thus could not correspond to the cytogenetically determined karyotypes. PMID- 7789182 TI - The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome. AB - The human calcitonin receptor (CTR) is a transmembrane peptide with dual action as a receptor for the hormone calcitonin and as an extracellular calcium sensor. Therefore, CTR dysfunction could lead to disorders of calcium metabolism associated with hypercalcemia, such as the Williams syndrome (WS). WS is a developmental disorder caused by a deletion at chromosome 7q11.23 that includes the elastin locus (ELN). We have mapped the CTR gene (CALCR) to chromosome band 7q21.3 by polymerase chain reaction and single-strand conformation analysis of somatic cell hybrids as well as fluorescence in situ hybridization (FISH) to metaphase chromosome spreads. Two-color FISH cohybridizing CTR and ELN probes confirmed that CALCR maps telomeric to ELN. Subsequent analysis of chromosome spreads from four WS patients revealed deletion of the ELN locus in all of them and normal hybridization of CTR probes to both chromosome 7 homologues, indicating that CALCR lies outside the deleted region. PMID- 7789183 TI - Chromosomal mapping of the genes GPRK5 and GPRK6 encoding G protein-coupled receptor kinases GRK5 and GRK6. AB - G protein-coupled receptor kinases (GRKs) play an important role in phosphorylating and regulating the activity of a variety of G protein-coupled receptors. Chromosomal mapping of the human genes for the two most recently identified members of the GRK family, GRK5 (GPRK5) and GRK6 (GPRK6), was accomplished by correlation of the presence of the GPRK5 and GPRK6 loci with specific chromosome regions in a rodent-human hybrid panel. These analyses revealed that GPRK5 maps to chromosome region 10q24-->qter while GPRK6 maps to 5q35. A GPRK6 related locus maps to 13pter-->q21. PMID- 7789184 TI - Localization of the human stem cell tyrosine kinase-1 gene (FLT3) to 13q12-->q13. AB - We have previously reported the cloning of stem cell tyrosine kinase-1 (STK-1, gene symbol FLT3), the human homolog of the mouse Flk2/Flt3 gene (Small et al., 1994). This growth factor receptor is expressed in CD34+ human bone marrow (stem/progenitor) cells. We have mapped the gene for STK-1 using PCR screening of a human-rodent somatic cell hybrid panel, and fluorescence in situ molecular hybridization (FISH) of STK-1 genomic probes to mitotic chromosomes of normal human lymphocytes. The results of both analyses show that the gene for STK-1 (FLT3) localizes to chromosome 13q12-->q13. PMID- 7789186 TI - Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents. AB - The Gfi1 gene encodes a zinc finger protein which binds DNA and is involved in transcriptional regulation. Gfi1 was assigned to the central portion of mouse Chr 5 by interspecific backcross mapping and to human chromosome band 1p22 and rat chromosome band 14p22 by fluorescence in situ hybridization (FISH). Comparative mapping data presented here describes a new syntenic region between man and rodents. PMID- 7789187 TI - Identification of p and q arms of the blesbok (Damaliscus dorcas phillipsi, Alcelaphinae) RBG-banded chromosomes with comparison to other wild and domestic bovids. AB - The RBG banded karyotype (2n = 38) of the blesbok (Damaliscus dorcas phillipsi) comprises 8 pairs of metacentric, 3 pairs of submetacentric and 7 pairs of acrocentric autosomes. The X and Y chromosomes are acrocentric. The 11 pairs of biarmed chromosomes correspond to Robertsonian translocations involving the chromosomes equivalent to goat and cattle chromosomes: 1;10, 4;5, 8;17, 7;9, 6;14, 13;15, 12;16, 20;22, 3;19, 2;27 and 11;23. The comparison of Blesbok karyotype with that of other species of Alcelaphinae and Hippotraginae reveals a high level of homoeology. PMID- 7789185 TI - Rabl orientation of CENP-B box sequences in Tupaia belangeri fibroblasts. AB - The chromosomes of the tree shrew Tupaia belangeri exhibit highly localized CENP B box sequences in the centromeric regions of most chromosomes. Telomeric sequences are present at the ends of all chromosomes and, in addition, at specific interstitial chromosomal sites that likely represent remnants of ancestral telomeres. This suggests that Robertsonian and tandem chromosome fusion events have occurred in the karyotypic evolution of Tupaiidae. In Tupaia skin fibroblasts CENP-B boxes are almost always clustered together at one pole of the interphase nucleus, whereas the telomeric domains are relatively evenly distributed throughout the whole nuclear volume. The observed orientation of the centromeres is reminiscent of the Rabl polarization of chromosomes; this is the first mammalian cell substrate in which such an higher-order chromosomal organization has been observed. CENP-B box sequences are found in several other mammalian species. The implications for recent parallel evolution of CENP-B binding motifs and concerted evolution of these sequences are discussed. PMID- 7789188 TI - Viability, development and incidence of chromosome anomalies of preimplantation embryos from XO mice. AB - We examined the viability and developmental status of XO embryos at preimplantation stage (day 3 of gestation) by assessing blastocyst formation and counting cell number using our XO mouse colony. We also examined the incidence of chromosome anomalies. Embryos from XO mice (XY, XX and XO) developed more slowly (in cell numbers and blastocoele formation) than those from XX mice (XY and XX). XO embryos also tended to develop more slowly than XX embryos in the XO group. Although litter size at the preimplantation stage of gestation was almost twice as large (12.7) as those at mid-gestation (7.6) and near-term (7.2) in this colony, the adjusted XY:XX:XO ratio (2.8:2.0:1.0) did not differ greatly. This indicates that almost half of the embryos must have been eliminated during the first half of gestation in the XO group, probably regardless of sex chromosome complements. Thus, we consider that maternal XO sex chromosome constitution is disadvantageous for the intrauterine development of the embryo during the early period of gestation. This may be related to precocious aging of XO mice. Further, we confirmed that a high incidence of abnormal karyotypes occurs in embryos from our XO mouse colony. PMID- 7789189 TI - Assignment of the gene (GLCLC) that encodes the heavy subunit of gamma glutamylcysteine synthetase to human chromosome 6. AB - Assignment of the human gene (GLCLC) that encodes the heavy or catalytic subunit of gamma-glutamylcysteine synthetase (glutamate-cysteine ligase; EC 6.3.2.2) to human chromosome 6 was accomplished by hybridization to Southern blotted somatic cell hybrid DNA. This assignment was confirmed by PCR from somatic cell hybrid DNAs. PMID- 7789191 TI - Function and content of maternal demands: developmental significance of early demands for competent action. AB - The sources and effects of mothers' demands upon children were examined during naturalistic interactions of 70 mothers and their 1 1/2-3 1/2-year-olds. Demands were categorized in terms of immediate function (e.g., do's vs. don'ts) and content area emphasized by mothers (e.g., competent action, appropriate behavior, caretaking). Children's age and oppositional behavior influenced the nature of mothers' demands. Mothers with authoritative child-rearing attitudes emphasized proactive, competence-oriented demands and avoided regulatory controls. Maternal demands for competent action (prosocial behavior, chores, cognitive/play) predicted enhanced compliance and fewer behavior problems at age 5. Demands focused on the regulation of personal and social behavior predicted more behavior problems at age 5. We propose that children's personal and social competence emerges from pressures for instrumentally competent behavior in a harmonious interactive context. PMID- 7789190 TI - Molecular characterization and refined genomic localization of three human potassium ion channel genes. AB - Potassium ion (K+) channels are essential for a variety of cellular functions in both excitable and non-excitable cells and are likely to be involved in the pathogenesis of some cardiovascular and neurological disorders. To be useful in candidate gene analysis of inherited diseases it is important to identify new K+ channel genes and localize these sequences on the human physical and genetic maps. Using fluorescence in situ hybridization (FISH), we mapped two new K+ channel gene containing cosmids, c2-3a and c9-2a, to chromosomes 1 and 19, respectively. Partial DNA sequencing (c2-3a) and restriction enzyme site analysis (c9-2a) established the uniqueness of each clone. We refined the localization of c2-3a, c9-2a and a previously described K+ channel gene KCNA5, (c7-2), by performing contour length measurements of hybridized metaphase chromosomes and determining the average FLpter% value (fractional length relative to the fixed reference point pter x 100%). When compared to ideograms of banded metaphase chromosomes, these FLpter% values correspond to 12p13.31-->p13.33, 1p13.1-->p21.1 and 19q13.32-->q13.33, respectively. Using FISH, each of these clones has been finely mapped to a different human chromosome indicating a significant dispersion of K+ channel sequences in the human genome. PMID- 7789192 TI - The determinants of coparenting in families with toddler boys: spousal differences and daily hassles. AB - In order to advance understanding of the phenomenon of coparenting, naturalistic observations of firstborn sons were undertaken when they were 15 months of age at a time when both parents were home and family life was demanding. Narrative records of coparenting events were scored to determine the frequency with which parents supported and undermined each other and to test two hypotheses pertaining to individual differences in coparenting: that greater differences between spouses in demographic factors, personality, styles of relatedness and child rearing attitudes would forecast more unsupportive and less supportive coparenting; and that the adverse effects of such spousal differences would be amplified by high levels of family stress, as indexed by frequency and intensity of daily hassles. Both hypotheses received support and are discussed in turn. PMID- 7789193 TI - Developmental change in infants' responses to stress. AB - Infant stress responses to a well-baby physical examination and inoculation were observed longitudinally at 2, 4, and 6 months of age. In general, there were cortisol increases over base to the procedures. Cortisol level and cortisol response decreased with age. These data indicate a developmental shift in adrenocortical functioning between 2 and 6 months of age. Further evidence for this shift was seen in the stability of individual responses between 4 and 6 months of age. Individual differences in both cortisol and behavioral responses showed the most stability between these 2 ages. Moreover, diurnal variation in baseline cortisol level was present only at 6 months of age. While a sizable minority of infants showed stress-related cortisol decreases to the procedures at a given age, there was no evidence for cross-age consistency in individual infants showing these cortisol decreases. PMID- 7789194 TI - What do children worry about? Worries and their relation to anxiety. AB - This study examined worry in elementary school aged children and its relation to anxiety. The study also examined whether parameters of excessive or dysfunctional worry could be delineated. Children from second through sixth grades (ages 7-12 years) were interviewed using a structured approach and completed several child anxiety measures. Parameters of worry assessed included: number of worries, areas of worry, intensity of worries, and perceptions of the frequency of worry events. Findings revealed few age-related differences but found that girls reported more worries than boys and that African-Americans reported more worries than white or Hispanic children. The three most common areas of worry involved School, Health, and Personal Harm. Anxiety was significantly associated with worry, providing empirical support for a link between these two constructs. Worry parameters, especially number and intensity of worries, could differentiate high and low anxious children in a normal school sample. Implications of these findings for understanding the role of worry in childhood anxiety are discussed. PMID- 7789195 TI - Priming of perceived control in young children as a buffer against fear-inducing events. AB - Young children (aged 5 and 6) watched videotaped fairy tales that acted to prime child control versus adult control over frightening events. Subsequently, they watched an ambiguous videotape of a child having a medical exam; tapes were varied for presence or absence of fear cues (facial expressions shown by actors). We predicted that children primed for child control versus adult control would show information-processing error patterns that paralleled those previously found for children who were dispositionally high or low in perceived control. As expected, children primed for child control showed processing enhancement whereas those primed for adult control showed processing deficits after witnessing fear cues. Attentional disengagement was found to mediate processing errors. Perceived control--dispositional or temporary--was interpreted as an important organizer of attention to and processing of potentially threatening events. PMID- 7789196 TI - Young children's understanding of the causes of anger and sadness. AB - This study investigated kindergarten children's understanding of the causes of anger and sadness. Previous research has shown that before 6 or 7 years of age, children have difficulty distinguishing hypothetical situations designed to evoke anger from those designed to evoke sadness. In this project, 80 kindergarten children (ages 5-1 to 6-5, M = 5-10) predicted and explained protagonists' emotional responses to a variety of hypothetical events. The results showed that intentional harm was not the feature young children used to distinguish anger from sadness. Children predicted anger most often when they believed that protagonists could change undesirable situations and reinstate their goals and when children focused on the person or conditions that brought about undesirable situations. Children predicted sadness most often when they believed that goal reinstatement was impossible and focused on the losses that would ensue as a result. PMID- 7789197 TI - Relational aggression, gender, and social-psychological adjustment. AB - Prior studies of childhood aggression have demonstrated that, as a group, boys are more aggressive than girls. We hypothesized that this finding reflects a lack of research on forms of aggression that are relevant to young females rather than an actual gender difference in levels of overall aggressiveness. In the present study, a form of aggression hypothesized to be typical of girls, relational aggression, was assessed with a peer nomination instrument for a sample of 491 third-through sixth-grade children. Overt aggression (i.e., physical and verbal aggression as assessed in past research) and social-psychological adjustment were also assessed. Results provide evidence for the validity and distinctiveness of relational aggression. Further, they indicated that, as predicted, girls were significantly more relationally aggressive than were boys. Results also indicated that relationally aggressive children may be at risk for serious adjustment difficulties (e.g., they were significantly more rejected and reported significantly higher levels of loneliness, depression, and isolation relative to their nonrelationally aggressive peers). PMID- 7789199 TI - Mother-child interaction quality as a partial mediator of the roles of maternal depressive symptomatology and socioeconomic status in the development of child behavior problems. Conduct Problems Prevention Research Group. AB - This investigation examined the relation between maternal depressive symptomatology and the development of externalizing behavior problems in children by incorporating mother-child interaction quality into a series of models. A representative sample of 376 first-grade boys and girls (mean age = 6.52) from diverse backgrounds (234 from the lowest 2 socioeconomic classes) and their mothers completed an interaction task designed to measure the quality of mother child interaction. Latent variable structural equations analyses revealed that mother-child interaction quality partially mediated the relation between maternal depressive symptomatology and child behavior problems even when the effects of socioeconomic status on both variables were taken into account. Although this model held for boys, girls, and Caucasians, the relation between maternal depression and interaction quality was not significant for African-Americans. Further investigation is required to understand the lack of generalizability of the model to African-American mother-child dyads. PMID- 7789198 TI - Meeting goals and confronting conflict: children's changing perceptions of social comparison. AB - It was proposed that previously observed grade-related changes in children's social comparison behavior could be explained by the changing goals and meanings children assign to this behavior. Specifically, it was suggested that, as children progress through the school system, they become increasingly aware of the negative and positive aspects of social comparison and adjust their behavior in response to this awareness, as well as to increasingly salient self-evaluation goals. To examine these propositions, 106 elementary school children were observed in their classrooms and interviewed once a year for 3 years. Consistent with previous research, overt forms of social comparison were most frequent among younger children, whereas subtle forms of social comparison were most frequent among older children. Furthermore, with increasing grade children were likely to view overt forms of social comparison negatively and subtle forms as useful in meeting self-evaluation goals. Additional analyses revealed little association between perceptions of social comparison and actual social comparison behavior, except that perceiving subtle social comparison as useful for self-evaluative goals predicted engagement in such behavior 2 years later. PMID- 7789200 TI - The academic lives of neglected, rejected, popular, and controversial children. AB - The purposes of this study were to examine academically relevant characteristics of different sociometric status groups and to learn about the academic orientations of behavioral subgroups of rejected children. Results from a sample of 423 sixth and seventh graders (ages 11-13) suggested that sociometrically neglected children have quite positive academic profiles. When compared with average status children, these students reported higher levels of motivation, were described by teachers as more self-regulated learners, as more prosocial and compliant, and as being better liked by teachers. Analyses of two behavioral subgroups of rejected children indicated that aggressive-rejected but not submissive-rejected children have problematic academic profiles. Relations of neglected and aggressive-rejected status to academic adjustment in young adolescents' lives is discussed. PMID- 7789201 TI - Socioeconomic disadvantage, proximal environmental experiences, and socioemotional and academic adjustment in early adolescence: investigation of a mediated effects model. AB - This study investigated interrelations among conditions of household socioeconomic disadvantage, proximal environmental experiences, and adaptational outcomes in a sample of 398 middle grade, early adolescents from a predominantly poor, rural area. Findings indicated that levels of disadvantage were related to both socioemotional and academic adjustment, with those from relatively disadvantaged backgrounds faring most poorly. Specifically, youth from homes in which adults were employed in low-income, unskilled occupations were found to have lower levels of school performance and achievement compared to those from homes in which adults were employed in higher paying semi-skilled or skilled/professional occupations. Further, youth from families in which neither parent had graduated from high school exhibited significantly worse socioemotional and academic adjustment than did those whose parents had higher educational levels. Youth who lived in relatively disadvantaged homes also reported more negative experiences of proximal environmental conditions relating to family and school contexts and greater exposure to stressful life events. Most notably, findings provided support for employing an ecological-mediational perspective to understand patterns of linkage between socioeconomic disadvantage and levels of adjustment. Support for this viewpoint included the finding that proximal environmental experiences were significant predictors of adolescent adjustment, independent of shared variance with conditions of household disadvantage, whereas conditions of disadvantage in several instances were no longer related significantly to indices of adjustment once their association with proximal environmental conditions was taken into account. The discussion considers implications for the targeting and scope of ecologically oriented approaches to preventive intervention. PMID- 7789202 TI - A contextual-moderator analysis of emotional autonomy and adjustment in adolescence. AB - This study investigated the relation between emotional autonomy, as measured by Steinberg and Silverberg's Emotional Autonomy Scale (EA), and adolescent adjustment as moderated by several individual, familial, and cultural contexts. Subjects were 96 adolescents (10-18 years old) and their mothers and teachers. Results indicate that when the affective nature of the parent-adolescent relationship is positive (e.g., maternal warmth is high or intensity of parent adolescent conflict is low), positive adolescent adjustment is more likely when adolescents report less emotional autonomy. On the other hand, when the family environment is more stressful, emotional autonomy is positively associated with adolescent adjustment. Findings suggest that higher scores on the EA scale index emotional detachment from parents and that such detachment is detrimental in supportive familial environments but adaptive in less supportive familial environments. That emotional detachment from parents appears to serve a protective function in certain stressful situations is viewed as analogous to the adoption of an avoidant attachment strategy during infancy. PMID- 7789203 TI - A twin-sibling study of observed parent-adolescent interactions. AB - Numerous behavioral genetic studies call attention to the strong and pervasive genetic influence on developmental characteristics. However, this research has been criticized for its use of poor environmental measures and a failure to examine the complex processes that are a hallmark of research in child development. This study addresses this criticism by examining the genetic and environmental components of parent-child interactions. Mother, father, and 2 adolescent siblings (10-18 years) from each of 675 families were observed interacting in 10-min dyadic problem-solving sessions. 6 groups of siblings that differed in genetic relatedness were examined (MZ and DZ twins, full siblings in nondivorced families; full, half, and unrelated siblings in stepfamilies). Results suggest a greater genetic component to adolescent behavior than to parent behavior. Both adolescent and parent behavior showed strong effects of nonshared environment, even after error of measurement was removed. PMID- 7789204 TI - The role of age and verbal ability in the theory of mind task performance of subjects with autism. AB - A number of studies have reported that most children with autism fail theory of mind tasks. It is unclear why certain children with autism pass such tests and what might be different about these subjects. In the present study, the role of age and verbal ability in theory of mind task performance was explored. Data were pooled from 70 autistic, 34 mentally handicapped, and 70 normal young subjects, previously tested for a number of different studies. The analysis suggested that children with autism required far higher verbal mental age to pass false belief tasks than did other subjects. While normally developing children had a 50% probability of passing both tasks at the verbal mental age of 4 years, autistic subjects took more than twice as long to reach this probability of success (at the advanced verbal mental age of 9-2). Possible causal relations between verbal ability and the ability to represent mental states are discussed. PMID- 7789205 TI - The organization of reactivated memory in infancy. AB - The specificity of memory retrieval by 3-month-old infants was examined in 3 experiments. All infants were trained in the mobile conjugate reinforcement paradigm to kick their feet to produce movement in an overhead crib mobile and were tested 2 weeks later. 24 hours prior to the test, subjects received a 3-min reminder treatment. The results of Experiment 1 demonstrated that only the moving training mobile alleviated forgetting after the 2-week retention interval; forgetting was not alleviated by exposure to the stationary training mobile or to the mobile stands and ribbon alone. The results of Experiments 2 and 3 demonstrated that, once retrieved, the reactivated memory was highly specific to the conditions of original training. Furthermore, the memory attributes that were the last to be forgotten (e.g., the general or global features) were the first to be retrieved following the reminder treatment. Conversely, those memory attributes that were forgotten first (e.g., the specific or local details) were the last to be retrieved. These findings have important implications for infant memory retrieval, reminiscence, and infantile amnesia. PMID- 7789206 TI - Leprosy control in China. Achievements and prospect. PMID- 7789207 TI - Progress of research on in vitro fertilization and embryo transfer in China. PMID- 7789208 TI - Progress of trauma research in China. PMID- 7789209 TI - Progress in lymphatic filariasis control in China. PMID- 7789210 TI - Structure-function interrelation and clinical effect of atrial natriuretic peptide (ANP). AB - Atriopeptin III (AP III) and its six analogues were synthesized by solid phase method and their diuretic and hypotensive activities were determined. Among these analogues, analogue [D-Ala-5, D-Arg-23] AP III was nearly 10 times as potent as AP III in diuretic activity while its hypotensive activity increased only 50% of that of AP III. Analogue des [Ser-15Gly-16Leu-17Gly-18Asn-20Ser-21] AP III was 15% as potent as AP III in diuretic activity, but it still maintained about 60% of the hypotensive activity of AP III. Meanwhile, we tried analogue [D-Ala-5, D Agr-23] AP III for the treatment of hypertensive syndrome in pregnancy and obtained some good results. PMID- 7789211 TI - Neurohypophysial AVP concentration in stroke patients. AB - Neurohypophysial arginine vasopressin (AVP) concentrations were determined by RIA in 9 patients with cerebral infarction, 11 patients with intracerebral hemorrhage, 5 patients with subarachnoid hemorrhage and 5 control subjects. The results showed that neurohypophysial AVP concentration in patients with cerebral infarction increased by 225.8% as compared with the control subjects (P < 0.05), and the AVP concentrations in patients with intracerebral and subarachnoid hemorrhage did not change significantly. Brain herniation as a result of intracranial hypertension, gastrointestinal bleeding and hyperglycemia (two clinical manifestations of stress) was seen more frequently in hemorrhagic stroke patients than in ischemic stroke patients. These findings suggest that the ischemic brain damage may contribute to the elevation of neurohypophysial AVP concentration in patients with cerebral infarction. PMID- 7789213 TI - Effects of daurisoline on cytosolic free calcium in fetal rat cerebral cells. AB - Cytosolic free Ca2+ ([Ca2+]i) was measured in dissociated cerebral cells isolated from fetal rats with the fluorescent indicater fura-2. Increase in [Ca2+]i occurred rapidly following exposure of the cells to 50 mmol/L KCl, 10(-7) mol/L Bay K 8644 or 200 mumol/L glutamate (Glu). [Ca2+]i elevated by K(+) depolarization was attenuated by pretreatment with 10(-7), 10(-6) mol/L daurisoline (Dau). The response of [Ca2+]i to K(+)-depolarization did not change when 10(-8) mol/L Dau was added. When 10(-8)-10(-6) mol/L Dau was added to the cell suspensions prior to exposure to Glu, the Glu-stimulated rises in [Ca2+]i were reduced significantly. However, Dau (10(-6), 10(-7) and 10(-8) mol/L) did not alter the response to Bay K 8644. These results indicate that Dau can inhibit the increase of [Ca2+]i in fetal rat cerebral cells induced by certain Ca2+ agonists, especially Glu, suggesting that this drug may have a protective effect against cerebral cellular injury. PMID- 7789212 TI - GM1 antibody in Guillain-Barre syndrome after Campylobacter jejuni infection. AB - Fecal culture of Campylobacter jejuni was prepared by the method of Skirrow, and serum class specific antibodies (IgG, IgM and IgA) to Campylobacter jejuni and serum class specific antibodies (IgG IgM) to GM1 were prepared with solid phase enzyme linked immunasorbent assay in 16 cases of Guillain-Barre syndrome (GBS), 32 controls with other neurological diseases (disease controls) and 90 normal controls. The results showed that the incidence of Campylobacter jejuni infection, especially recent infections, in the group with Guillain-Barre syndrome was much higher than that in the two control groups, and that the positive rate of GM1 antibody was also much higher in the GBS group than in the two control groups. The results suggest that Campylobacter jejuni infection may be one of the important precipitating factors of Guillain-Barre syndrome and play an important role in the epidemiological pattern of Guillain-Barre syndrome in China. It damages the myelin of peripheral nerves through induction of GM1 antibody production. PMID- 7789214 TI - Identification and classification of Neisseria gonorrhoeae by RAPD fingerprinting. AB - Using the RAPD method, we identified and classified Neisseria gonorrhoeae on the basis of the DNA level. Except OPG20 the other 19 primers of OPG arbitrary primer kit showed informative arrays of amplified prominent segments. Most of the segments were common to all three Neisseria gonorrhoeae groups; some segments were amplified from two groups or only one group so that the fingerprint maps of different Neisseria gonorrhoeae groups were distinctive. Based on these findings, i.e. on the genomic level, we can classify the three Neisseria gonorrhoeae groups. Using OPG10 and OPG11 to amplify the five Neisseria species, we found marked diversity among them, which made it easy for us to identify Neisseria gonorrhoeae from four other Neisseria species. The use of the RAPD method needs some special reaction conditions, e.g. annealing temperature that should not be too low or too high and should be consistently stable. The quality of Taq polymerase is also very important. The reproducibility of the results under these conditions was very good. PMID- 7789215 TI - Extensive wound excision in shock stage in patients with major burns. AB - To stop excessive plasma loss, alleviate noxious effects of devitalized tissues on the body and shorten the hospitalization time, we performed extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients aged 9-45 years (26.1 +/- 7.9 years), with a mean total burn area of 63.2% +/- 18.1% TBSA, and full-thickness injury involving 35.9% +/- 19.6% TBSA. The first escharectomy was done at 24.1 +/- 13.9 hours postburn, and excision area averaged 32.3% +/- 6.7% TBSA (24%-46%). In 15 of them, Swan-Ganz catheter was introduced to monitor the hemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients aged 11-50 years (30.4 +/- 11.7 years), in whom escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, shorter than that of group B patients (40.1 days). The duration of hemoconcentration was shorter in group A. The amount of blood transfusion was almost 700 ml less in group A during the first two weeks. Less antibiotics were used with fewer visceral complications in group A. We believe that escharectomy during the burn shock stage is feasible. PMID- 7789216 TI - Changes of gastric acid secretion and somatostatin after Roux-en-Y cholangiojejunostomy. AB - The authors studied the changes of gastric acid secretion and determined the levels of somatostatin (SS) and gastrin (Gn) in blood, gastric juice and pyloric antrum in 28 patients Roux-en-Y with cholangiojejunostomy (CJR-Y). Gastric acid hypersecretion was identified, and the level of SS was found dropped while the content of Gn increased in these specimens. It was considered that the reduction of SS synthesis and secretion might have a key effect on the mechanism of secondary gastric acid hypersecretion in patients after CJR-Y. PMID- 7789217 TI - Endogenous porphyrins in murine skin and transplanted PAM-212 squamous cell carcinoma tissues after injection of delta-aminolevulinic acid. AB - After intraperitoneal (IP) injection of delta-aminolevulinic acid (ALA), the endogenous porphyrins in murine skin and tumor tissues were determined by a method involving solvent and acid extractions. The results showed that the total amount of porphyrins in the tumor tissues after ALA injection was much higher than that in the skin from the same mice, although the amount of porphyrins in the skin from the ALA-injected mice was higher than that from the saline-injected (control) mice. The porphyrins in the tumor were mostly protoporphyrin and coproporphyrin, with only a small amount of uroporphyrin. The optimum period for porphyrin accumulation in the tumor as well as in the skin was 1 hour after the injection of ALA. As the period was extended to 3 and 6 hours, the amount of porphyrins in these tissues decreased considerably. These findings could be valuable for further application of ALA in the photodynamic therapy of skin cancer. PMID- 7789218 TI - The safety and efficacy of streptokinase in coronary reperfusion in patients with acute myocardial infarction. PMID- 7789219 TI - Progress in surgical treatment of hydatid diseases in China. A clinical analysis of 22,005 surgical cases. AB - Altogether 27,716 cystic hydatid cases and 445 alveolar hydatid cases clinically diagnosed and surgically treated in China were retrospectively studied. In accordance with the parasitic sites of the hydatid cysts and the various pathological types, different surgical procedures were adopted. In an attempt to prevent intraoperative accidents and postoperative complications, continued improvements in operational techniques have been made. Different surgical procedures were evaluated for their advantages and disadvantages as well as their indications. According to the pathological changes of the residual cavities of ectocysts, different measures were adopted. In screening operations, injection of antihydatid drug into hydatid cysts followed by oral administration of this drug was used to prevent relapses. The therapeutic effect of all these measures has been proved satisfactory by follow-up studies. This indicates that the progress in surgical treatment of cystic hydatid disease during the recent 10 years has been attaining to the objectives of shortening the duration of treatment, decreasing the postoperative recurrence rate and increasing the cure rate. In some hospitals, no operative death and relapse of cyst growth have been reported in nearly 1,000 surgical cases of cystic hydatid disease. Only 10.8% of the 445 alveolar hydatid cases underwent radical operations and the prognoses were unfavourable. This was due to the absence of symptoms in early stages of the disease which often made the patients miss the chance for radical operation in hospitals. PMID- 7789220 TI - Serological survey of nasopharyngeal carcinoma in 21 cities of south China. AB - This paper reports the results of serological survey of 318,912 persons for nasopharyngeal carcinoma (NPC) in 21 cities and counties of south China. There were 8,441 persons with positive VCA-IgA antibody (single item positive) of EB virus (EBV), with a rate of 2.65%. In these VCA-IgA positive persons, 287 persons also had positive EA-IgA (double items positive) of EBV. The overall positive rate was 0.09%. 100 cases of NPC were found and 87 of them (87.0%) were in early stage. NPC found in the group with single item positive accounts for 1.19%, but the rate in the group with double items positive was 19.16% (55 cases). In NPC patients with double items positive, 49 cases were in early stage (89.1%). In 100 cases of NPC found, 45 cases appeared with negative EA-IgA, only with positive VCA-IgA, which indicated that for diagnosis of NPC, sensitivity of EA-IgA was lower than that of VCA-IgA, but its specificity was higher. Therefore, both can increase the detecting rate and early diagnosis rate of NPC. The age of people checked varied with different antibody positive rate and NPC detecting rate. The three items showed a positive correlation. The results are compatible with those of the prospective study for NPC in Wuzhou City, Guangxi, China. The method for NPC serological diagnosis can be extended and applied to raise the NPC detecting rate and early diagnosis rate at secondary prevention. And, it is further proved that there is a close relationship between NPC and EBV. PMID- 7789221 TI - Epidemiology of Helicobacter pylori infection in the People's Republic of China. AB - This paper presents a general review of the studies on the epidemiology of H. pylori infection in China. Among 3,519 dyspeptic individuals presenting for endoscopy, H. pylori detectable rate was 61.2%. A higher prevalence of infection was found in patients with peptic ulcer. The prevalence of gastric metaplasia was 82.5% in patients with duodenal ulcer, 53.1% in duodenitis and 34.5% in normal duodenal mucosa. H. pylori infection is significantly more common in gastric cancer patients (58.9%) than in the matched controls (42.5%). Endoscopic studies performed on asymptomatic volunteers aged 10-25 showed that the prevalence of gastritis and H. pylori was 45%-84% and 42%-67% respectively. Large scale prospective studies of the possible role of H. pylori in gastric cancer in populations with various gastric cancer mortality rates using ELISA assays showed a significant geographical association between gastric cancer mortality and the prevalence of H. pylori infection. H. pylori infection is acquired at an earlier age and has a higher prevalence in the high gastric cancer risk areas than in the low risk areas. H. pylori was detected in human saliva and dental plaque by PCR. H. pylori-like organisms were successfully isolated by culture and detected by nested PCR in the gastric mucosa of pigs and cats. Intrafamilial clustering of H. pylori infection was observed. PMID- 7789222 TI - The changing cancer spectrum and incidence in Shanghai area. PMID- 7789223 TI - Cognitive impairment in multiple cerebral infarction. PMID- 7789224 TI - [Experimental study on immediate endosseous implantation]. AB - Screw type implants (ITI series) were implanted into the socket of extracted teeth of adult dogs to investigate the histologic recovery process of implantation. Two groups of immediate implantation. (with or without filling of cancellous bone chips) were performed, with a follow-up period of one month and three months. Results showed that marked immature new bone formation was found one month later after implantation. The amount of new bone in the group with cancellous bone implantation was much more than that in the group without bone chips. Mature new bone was observed three month later after operation, no marked difference was found in the amount of new bone between the two groups. PMID- 7789225 TI - [The changing of orofacial structure by bite opening with Begg technique]. AB - Cephalometric study of 30 deep-bite cases treated with extraction of four first premolars and Begg stage I appliance shows that the bite opening consists of not only intrusion of the upper and lower incisors but also extrusion of the upper and lower molars, furthermore, the lower incisors depressed more than the upper ones and the lower molars are elevated more than the upper ones. The moving type of teeth, the changing of base bone and soft tissue profile are also discussed in this article. PMID- 7789226 TI - [A primary study of classification of functional speech problem after cleft palate repair]. PMID- 7789227 TI - [Expression of proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma of the oral cavity]. AB - Proliferating cell nuclear antigen (PCNA) was identified by immunohistochemistry in 52 cases. PCNA-positive cells had been detected in the basal cells of normal epithelium known to contain proliferating cells. PCNA scores of normal epithelium was 1 as "low", and carcinomas were 3 or 4 as "high". The PCNA scores of high grade carcinoma was significantly higher than the low-grade carcinoma. The study shows that expression of PCNA correlated with carcinoma grade. PMID- 7789228 TI - [Mandibular drift-orthodontics after first premolar extraction]. PMID- 7789229 TI - [Evaluation of presurgical orthodontic correction of the mandibular prognathism]. AB - The aim of this study was to evaluate the effects of presurgical orthodontic correction of the mandibular prognathism. The sample consisted of two groups of surgical cases. The cases of the mandibular prognathism in group I with lower anterior dental compensation received presurgical orthodontic decompensation, and the cases in group II without lower anterior dental compensation did not receive presurgical orthodontic decompensation. The results showed that before presurgical orthodontic treatment, significantly differences existed between the two groups variable ILi/OL and ANB. After presurgical orthodontic correction lower incisors position in group I was very close to that in the group II, this means that the presurgical orthodontic treatment significantly changed the position of the lower incisors. PMID- 7789230 TI - [Application of T-subgroup cells assay in the immunology of oral-maxillofacial cancer]. AB - We report on T-subgroup cells in 70 cases of oral-maxillofacial cancer determined by T-monoclone antibody-OKT system. The results are as follows: CD3, CD4/CD8 value of cancer patients was decreased significantly, compared with that of health or oral benign tumor patients. CD8 was significantly increased (P < 0.001); however, CD8 was decreased and CD4/CD8 ratio was increased after operation. 20 cases underwent the dynamic testing, determined in 1 week, 1 and 3 month. The results are as follows: CD3, CD4, CD4/CD8 values were increased gradually and CD8 was decreased gradually in 17 cases of curative patients, but CD4, CD4/CD8, values were decreased and CD8 was increased significantly in 3 cases of metastased patients. Our conclusion is that determination of T-subgroup cells is of reference value for monitoring and treating cancer patients. PMID- 7789231 TI - [The effect of sagittal split ramus osteotomy advancement and setback mandible on occlusal force and masticatory efficiency]. AB - 21 patients (mandibular prognathism = 11, mandibular retrognathism = 10) whose occlusal force and masticatory efficiency were measured and analysed preoperatively, three and six months following sagittal split ramus osteotomy. The result shows that, in individuals with mandibular retrognathism treated by lengthening of the mandible, the occlusal force and masticatory efficiency would decrease, in individuals with mandibular prognathism treated by reduction in mandibular length, the occlusal force and masticatory efficiency would increase. There is no linear correlation relationship between the change of the occlusal force and the movement of the angle and the distance of the mandible. PMID- 7789233 TI - [A preliminary evaluation of bone matrix gelatin in clinical application to oral and maxillo-facial surgery]. PMID- 7789234 TI - [Relations between human papillomavirus and oral cancers using of nucleic acid hybridization]. PMID- 7789232 TI - [The effect of measuring the curvature of soft palate to determine the position of posterior peripheral seal]. AB - This study was undertaken to determine the feasibility of the surveyor of curvature in fabricating a full upper denture. 48 cases were investigated to determine the position of the posterior peripheral seal with the instrument. The results showed that the retention of the full upper denture was greater than that of the control-team. This method is more suitable for the patients with lower flat or higher palatal vault. PMID- 7789235 TI - [Relationship between levels of aspartate aminotransferase in gingival crevicular fluid and periodontal disease activity]. AB - This paper describes a longitudinal study in which clinical parameters and aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) were monitored bimonthly over a 6-12 months period in 970 sites from 7 treated periodontitis patients. In this study, 21 out of 970 sites exhibited new attachment loss (AL) of at least 2mm between two consecutive visits. The GCF-AST levels and clinical parameters at sites with active tissue destruction (> or = 2mm AL within two months) were significantly higher than those at control sites on the same tooth. The GCF-AST levels and clinical parameters at sites with active tissue destruction decreased significantly after re-treatment. The measurement of GCF-AST could be an useful adjunctive criterion for detection of disease activity. However, it seems to be unsatisfactory in predicting disease activity. PMID- 7789236 TI - [HPLC monitoring and pharmacokinetic study of crevicular fluid concentrations after a single oral dose metronidale]. PMID- 7789237 TI - [Computerized tomography diagnosis of cervical node metastasis in head and neck cancers]. PMID- 7789238 TI - [Usage of the geno-toxicological studies in the biological evaluation of dental materials]. AB - The salmonella mutagenicity test (Ames test), the Bacillus subtilis repair test and SOS chromotest are three sorts of sort-term mutagenic test, which were developed recently and had their individual terminal point to examine genotoxins. A battery of short-term tests was made up of these three mutagenic tests to examine the mutagenicity of formaldehyde, glutaraldehyde and resorcinal. The results verified formaldehyde and glutaraldehyde were genetoxins, and discovered resorcinal not only had no mutagenicity, but also had the antimutagenicity to some genotoxic agents. In addition, the methods of three tests were described and the use of the battery was introduced and evaluated. PMID- 7789239 TI - Bridging the gap between cytopathology and surgical pathology. PMID- 7789240 TI - Diagnosis of lymphoma, leukemia, and metastatic tumor involvement of the cerebrospinal fluid by cytology and immunocytochemistry. AB - Fifty-five cerebrospinal fluid (CSF) specimens from 42 patients with suspected meningeal tumor involvement were reviewed. Cytology in conjunction with immunocytochemistry identified 26 CSF specimens as malignant. There were fifteen cases of lymphoma, four cases of leukemia, two cases of carcinoma, and two cases of melanoma. A monoclonal light chain expression was demonstrated in nine out of eleven B cell lymphomas. The three T-cell lymphomas all expressed pan T markers (CD 3) and two the T-helper antigen (CD 4). One patient had meningeal involvement of a true histiocytic lymphoma which was identified by its large atypical cells which were positive for alpha-1-anti-trypsin and muramidase. In four patients with a primary diagnosis of acute lymphoblastic leukemia, CSF involvement was confirmed by the demonstration of blasts with CD 10 (cALLA) or light chain restriction. Epithelial or melanocytic markers were demonstrated on the tumor cells in CSF from the remaining four patients. In 29 CSF specimens a diagnosis of reactive lymphocytosis was made using cytomorphology which mostly was characterized by macrophages mixed with small mature lymphoid cells. Immunologic evaluation showed that these mature cells were CD 10 negative T-cells and only few specimens contained polyclonal B-cells. The subsequent clinical course of these patients showed no evidence of CNS malignancy. It is concluded that cytology should be used in conjunction with immunocytochemistry to accurately evaluate CSF specimens from patients with possible malignant meningitis. PMID- 7789241 TI - Tuberculous lymphadenitis: extended cytomorphologic features. AB - In tuberculous lymphadenitis, FNAC smears sometimes reveal only caseous necrosis without epithelioid cell granuloma. They pose a diagnostic problem, if AFB staining is negative. The diagnostic clue noticed in these cases was presence of multiple pink, homogenous structures with irregular shape and well-defined margins: "eosinophilic structures" (ES). The purpose of the present study is to find out the nature of ES and their role in the diagnosis of tuberculosis. Seventy FNAC smears from documented cases of tuberculous lymphadenitis were classified according to their cytomorphological features. The association and relation of ES with other morphological criteria was noted. Immunoperoxidase staining was performed to find out the reactivity of ES to tuberculous antigen. Its intensity of positivity was compared with epithelioid cell granuloma and degenerating granuloma. It was concluded that ES are degenerated granuloma and thus form an extended diagnostic criterion. PMID- 7789242 TI - Effusion cytology in Burkitt's lymphoma. AB - The American form of Burkitt's lymphoma is a high-grade malignancy which usually involves the abdomen in children and young adults. There is only a limited literature which describes the cytologic features of Burkitt's lymphoma in serous effusions. We present three children with Burkitt's lymphoma initially diagnosed by effusion cytology. The first patient, an 11-yr-old boy, presented with bilateral pleural effusions, ascites, and abdominal masses and had diagnostic pleural fluid cytology without tissue confirmation (ultrastructural examination was performed on the effusion specimen). He died 7 months after the initial diagnosis. The second patient, a 9-yr-old boy, presented with ascites and abdominal masses and had diagnostic peritoneal fluid cytology with a subsequent confirmatory chest wall biopsy. The third patient, a 16-yr-old girl, presented with a 2-month history of irregular menses, a large pelvic mass, lymphadenopathy, and liver masses. Although an ovarian malignancy was clinically suspected, cytologic examination of her peritoneal fluid revealed Burkitt's lymphoma. Surgical exploration revealed involvement of her right ovary, cecum, and terminal ileum. The second and third patients are currently alive with no apparent disease following chemotherapy. In all three patients, effusion cytology revealed Burkitt's lymphoma, characterized by a uniform population of non-cohesive lymphoid cells with noncleaved nuclei, prominent multiple nucleoli, and scanty-to moderate basophilic cytoplasm. Cytoplasmic and/or nuclear vacuoles were also seen, more prominent in Diff-Quik-stained, air-dried smears. These cases demonstrate the importance of recognizing the cytologic features of Burkitt's lymphoma, as serous fluid may be the initial diagnostic specimen. PMID- 7789243 TI - Pulmonary lymphoma in cardiac transplant patients treated with OKT3 for rejection: diagnosis by fine-needle aspiration. AB - At Hines VA Hospital, three out of 38 cardiac transplant patients, who were 9, 10, and 14 mo post-surgery and treated with immunosuppressive drugs, including OKT3 prophylaxis for acute rejection, developed a solitary pulmonary nodule. Fine needle aspiration biopsy of the nodules in these three patients revealed a hypercellular, monotonous population of large lymphoid cells. These abnormal cells were isolated, with small aggregates occasionally seen. The nuclear membranes were irregular, the chromatin was finely granular, nucleoli were prominent, and mitotic figures were frequently noted. The cells were immunoreactive to leukocyte common antigen and B-lymphocyte. Lambda light chain immunoglobulin was positive in one case, kappa in the second case, and neither light chains in the third patient. By electron microscopy in one case, the cells were large immature lymphoid cells with immunoblastic features. Subsequent tissue studies, complemented by frozen section immunostaining, flow cytometry, and phenotyping, reaffirmed the diagnosis of malignant lymphoma. It appears that OKT3 therapy increases several fold the risk of lymphoma's developing in cardiac transplant patients. Preliminary published reports have also recommended close surveillance of patients receiving OKT3 for early indications of lymphoproliferative disorder and a reevaluation of the risk vs. benefit for the prophylatic use of OKT3. PMID- 7789244 TI - Antigen expression of alveolar macrophages in smokers and patients with lung diseases. AB - Alveolar macrophage function was studied immunocytochemically using three monoclonal antibodies--macrophage CD 68 KP 1 (M), protein CD 11C (P), and anti elastin (EL)--and three polyclonal antibodies--lysozyme (LZ), alpha-1-antitrypsin (AAT), and alpha-1-antichymotrypsin (AACT). The material for study was smears obtained from bronchial washings from 15 healthy persons and 60 patients with respiratory infections or primary or secondary malignant lung infiltration. Eight of the healthy group and 40 of the patient group were smokers (SM). The percentage of cells obtained from the washings which were macrophages was also measured. The intensity of staining reactions for each of the six antigens was noted and in general more intense staining was noted in smokers than in non smokers. More intense staining was observed in patients with pulmonary infections (group II PI) and metastatic pulmonary infiltrations (group IV MP Ca) than in controls (group IC), while patients with primary lung cancer (group III PP Ca) had highly reduced staining reactions. The number of macrophages was similarly increased in all groups in comparison with the IC group for non-smokers and in all groups except III PP Ca for smokers. It is concluded that smoking, pulmonary infections, and metastatic infiltration of the lung are associated with an increase in the number and activity of alveolar macrophages, while patients with primary lung cancer have an increase in the number of macrophages which are functionally incompetent. PMID- 7789246 TI - Confocal microscopy: a new horizon for cytology. PMID- 7789245 TI - Confocal microscopy of false-negative breast aspirates. AB - Even when using a novel optimized FNA-21 for breast fine-needle aspiration biopsy, our series of 163 breast lesions with consecutive histology, including 110 carcinomas, contained eight cancer cases with a negative cytologic diagnosis. Two consisted exclusively of thick, undiagnosable epithelial fragments and were devoid of detached malignant cells on which the proper diagnosis could have been made. Optical sectioning of the original smears by the confocal microscope allowed us to reclaim from these epithelial fragments the diagnostic abnormal chromatin patterns, even in the air-dried smears. In the thin optical sections the cancerous tubular or cribriform growing pattern was visualized. The high spatial resolution of the confocal microscope can be further exploited with the application visualization system (AVS). The AVS three-dimensional reconstructions allow us to see the surface of these malignant cells in a detail approaching that of scanning electron microscopy. Furthermore, the internal aspects of the malignant nuclei can be visualized with these techniques. PMID- 7789247 TI - Mycoses of the breast: diagnosis by fine-needle aspiration. AB - Fungal infections of the breast are unusual and may clinically mimic carcinoma. When studied by fine-needle aspiration (FNA), such masses may yield necrosis, granulomatous inflammation, reactive histiocytes, and atypical epithelial cells. Cohesive groups of atypical epithelial cells featured nuclear enlargement and overlapping, as well as prominent nucleoli. The organisms may be widely scattered, so that careful evaluation was required for their identification. In concert with provocative clinical findings, these features may lead to an erroneous diagnosis of malignancy. We describe three women with mycotic masses of the breast initially studied by FNA. The first patient presented at age 31 with a large, firm breast mass, chest wall extension, and radiographic evidence of vertebral bone involvement. FNA was requested to confirm the clinical diagnosis of advanced breast carcinoma. In addition to the atypia described above, the smears showed yeast forms indicative of blastomycosis surrounded by neutrophils. She remains well, following antifungal treatment. The second case of Blastomycosis was diagnosed by FNA of a breast mass in a 64-yr-old woman, who also responded to treatment. The third patient's preoperative needle aspiration showed granulomas, but no organisms were identified, even with special stains; silver stains of surgically excised tissue showed histoplasmosis. PMID- 7789248 TI - Nocardiosis diagnosed by lung FNA: a case report. AB - A 63-yr-old woman with systemic lupus erythematosus (SLE) diagnosed 12 mo previously and treated with prednisolone and cyclophosphamide presented with recent fever and dyspnoea. The etiology of a 3 cm diameter centrally cystic coin lesion in the lower lobe of the left lung was obscure. Blood cultures and sputum examination had been non-contributory, and the diagnosis of Nocardia asteroides infection was initially made by cytologic examination of material obtained by lung fine-needle aspiration (FNA). It is notoriously difficult to detect this organism by conventional sputum examination or with histologic sections, and it has rarely been detected by lung FNA. If this organism is demonstrated, appropriate microbiologic cultures for confirmation and susceptibility testing should be instituted. Long-term antimicrobial therapy is needed. In this case, complete resolution of the lung lesion followed 5 mo of therapy. PMID- 7789249 TI - Diagnosis of metastatic appendiceal adenocarcinoid in liver by fine-needle aspiration cytology. AB - A 70-yr-old woman presented with symptoms clinically attributed to acute appendicitis. An adenocarcinoid tumor of the appendix was resected, followed by right hemicolectomy with negative lymph nodes. Seven years later, a fine-needle aspiration biopsy was performed on one of multiple hepatic nodules, revealing metastatic adenocarcinoid. The cytopathologic features of the metastatic tumor are described. PMID- 7789250 TI - Glycogen-rich clear cell carcinoma of the breast: report of a case with fine needle aspiration cytology and immunocytochemical and ultrastructural studies. AB - Fine-needle aspiration cytology, immunocytochemistry, and electron microscopic findings are described in a case of glycogen-rich clear cell carcinoma of the breast. The aspirate contained many small and large papillary cell groups and numerous single tall columnar cells with apical cytoplasmic projections and mild to moderate degree of nuclear pleomorphism. Cytochemical localisation of glycogen and immunostaining on air-dried smears with CEA and actin monoclonal antibodies permitted the correct identification and differential diagnosis of the tumor. Electron microscopic examination of the resected specimen confirmed the diagnosis of glycogen-rich clear cell carcinoma. The differential diagnosis and potential diagnostic pitfalls are discussed, and recommendation are offered to prevent misdiagnosis. PMID- 7789251 TI - Calcium oxalate crystals in benign breast cyst fluid. AB - We have recently observed a strongly birefringent material of varying shapes and sizes in a benign breast cyst fluid specimen from a 52-yr-old woman with suspicious mammographic microcalcifications. The finding of calcium oxalate crystals in the breast cyst fluid should be regarded as a recognition of a particular type of calcification, easily overlooked with the conventional light microscopy. To date, we are unaware of any cytologic reports of this type of calcification in the breast. PMID- 7789252 TI - Calcifying epithelial odontogenic tumor (Pindborg's tumor) on fine-needle aspiration biopsy smears: a case report. AB - A 44-yr-old woman with a long-standing history of painful mandibular swelling was hospitalized for the diagnostic evaluation of an osteolytic mandibular lesion in the premolar-canine area. Fine-needle aspiration biopsy (FNAB) was performed and cytologic smears were characterized by clusters, sheets, and rare isolated pleomorphic cells of the squamoid type, blocks of amorphous material encircled by fibroblasts, and occasional calcifications. A cytological diagnosis of Pindborg's tumor was made, which was confirmed by histopathological examination. Evaluation of DNA ploidy by semiautomated image cytometry produced an aneuploid histogram. The patient is free of residual neoplasm at a 12-mo post-operative interval. The cytological differential diagnosis of this rare odontogenic neoplasm is discussed briefly. PMID- 7789253 TI - Sialadenitis with crystalloid formation: a report of six cases diagnosed by fine needle aspiration. AB - Six cases of sialadenitis diagnosed by fine-needle aspiration contained large numbers of crystalloids. Light microscopy, ultrastructure, and chemical analysis suggest that the crystalloids represent crystallized salivary alpha-amylase. The inflammatory swelling may mimic benign and/or malignant neoplasms of the salivary glands. Drainage and/or antibiotic therapy may allow surgery to be avoided in these patients. PMID- 7789254 TI - Utilization of fine-needle aspiration biopsy in the diagnosis of metastatic tumors to the pancreas. AB - There is relatively little information concerning the use of fine-needle aspiration biopsy (FNAB) to diagnose a mass in the pancreas that is secondary to metastatic tumor. This study reviews the incidence and types of neoplasms which metastasize to the pancreas and assesses the contribution FNAB can make in their diagnosis. Of 117 radiologically guided FNABs of the pancreas, 11% (n = 13) showed metastatic malignancy. Nine patients had a previous history of malignancy while four patients presented with a pancreatic mass and were subsequently found to have wide-spread malignant disease. The majority of metastatic lesions were epithelial (77%, n = 10). Patient outcomes were generally poor (mean survival 2.8 mo). Metastases to the pancreas occur from a variety of primary sites and should be considered in patients with a pancreatic mass and a history of prior malignancy. FNAB is useful in diagnosing these metastases and this is clinically important because of their poor prognosis. PMID- 7789255 TI - OV632 as a possible marker for malignant mesothelioma: high expectations; low specificity. PMID- 7789256 TI - Aspiration cytodiagnosis of crystalloids in a sudden swelling of parotid gland. PMID- 7789257 TI - Clear cell carcinoma of the minor salivary gland metastasizing to the thyroid. PMID- 7789258 TI - A Dutch view on American cytology in the headlines. PMID- 7789259 TI - The C. elegans neuronally expressed homeobox gene ceh-10 is closely related to genes expressed in the vertebrate eye. AB - We describe the homeobox gene ceh-10 from the nematode Caenorhabditis elegans. The homeodomain of ceh-10 is closely related to the homeodomains of two genes recently cloned from the vertebrate retina, Chx10 from mice and Vsx-1 from goldfish. We show that the sequence conservation extends well beyond the homeodomain and includes a region (named the CVC domain) of roughly 60 amino acids immediately C-terminal to the homeodomain. As assayed in transgenic worms, the promoter region of ceh-10 directs expression of a lacZ reporter gene to a small number of neurons. We draw a parallel between the bipolar cells of the inner nuclear layer of the vertebrate retina, which express Chx10 and Vsx-1, and an interneuron in C. elegans called AIY, which expresses ceh-10. AIY receives synaptic input from a sensory cell, just as do bipolar cells of the vertebrate retina. In C. elegans, the sensory cell AFD is not known to be photosensitive but is known to be thermosensitive; moreover, a cell with similar position in the amphids of other nematodes has been suggested indeed to be photosensitive. Our results emphasize the highly conserved nature of sensory regulatory mechanisms and suggest one way in which photosensitive organelles might have originated in evolution. PMID- 7789260 TI - Wingless induces transdetermination in developing Drosophila imaginal discs. AB - Drosophila imaginal discs, the precursors of the adult fly appendages, have been the subject of intensive developmental studies, particularly on cell determination. Cultured disc fragments are recognized not only for the ability to maintain their determined state through extra cell divisions but also for the ability to transdetermine, or switch to the determined state of a different disc. An understanding of transdetermination at a molecular level will provide further insight into the requirements for maintaining cell determination. We find that ectopic expression of the Drosophila gene wingless induces transdetermination of foreleg imaginal disc cells to wing cells. This transdetermination occurs in foreleg discs of developing larvae without disc fragmentation. The in situ transdetermining cells localize to the dorsal region of the foreleg disc. This wingless-induced transdetermination event is remarkably similar to the leg-to wing switch that occurs after leg disc culture. Thus we have identified a new approach to a molecular dissection of transdetermination. PMID- 7789261 TI - Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. AB - The low-affinity receptor for leukemia inhibitory factor (LIFR) interacts with gp130 to induce an intracellular signal cascade. The LIFR-gp130 heterodimer is implicated in the function of diverse systems. Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth. PMID- 7789262 TI - Neurotrophins affect the pattern of DRG neurite growth in a bioassay that presents a choice of CNS and PNS substrates. AB - Neurons can be categorized in terms of where their axons project: within the central nervous system, within the peripheral nervous system, or through both central and peripheral environments. Examples of these categories are cerebellar neurons, sympathetic neurons, and dorsal root ganglion (DRG) neurons, respectively. When explants containing one type of neuron were placed between cryosections of neonatal or adult sciatic nerve and neonatal spinal cord, the neurites exhibited a strong preference for the substrates that they would normally encounter in vivo: cerebellar neurites generally extended only on spinal cord, sympathetic neurites on sciatic nerve, and DRG neurites on both. Neurite growth from DRG neurons has been shown to be stimulated by neurotrophins. To determine whether neurotrophins might also affect the substrate preferences of neurites, DRG were placed between cryosections of neonatal spinal cord and adult sciatic nerve and cultured for 36 to 48 hours in the presence of various neurotrophins. While DRG cultured in NGF-containing media exhibited neurite growth over both spinal cord and sciatic nerve substrates, in the absence of neurotrophins DRG neurites were found almost exclusively on the CNS cryosection. To determine whether these neurotrophin-dependent neurite patterns resulted from the selective survival of subpopulations of DRG neurons with distinct neurite growth characteristics, a type of rescue experiment was performed: DRG cultured in neurotrophin-free medium were fed with NGF-containing medium after 36 hours in vitro and neurite growth examined 24 hours later; most DRG exhibited extensive neurite growth on both peripheral and central nervous system substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789263 TI - Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of the alpha PS1 integrin subunit. AB - We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to if (alpha PS2) and mys (beta PS) mutants, most mutant mew embryos hatch, to die as larvae. Mutant mew embryos display abnormal gut morphogenesis but, unlike mys or if embryos, there is no evidence of defects in the somatic muscles. Thus, the complementary distributions of PS1 (alpha PS1 beta PS) and PS2 (alpha PS2 beta PS) integrin on tendon cells and muscle, respectively, do not reflect equivalent requirements at the myotendinous junction. Dorsal herniation, characteristic of the mys lethal phenotype, is not observed in mew or in mew if embryos. Clonal analysis experiments indicate that eye morphogenesis is disrupted in mew clones, but if clones in the eye are relatively normal in morphology. Adult wings display blisters around large dorsal but not ventral mew clones. In contrast to dorsal mys clones, small mew patches do not necessarily display morphogenetic abnormalities. Thus, another integrin in addition to PS1 appears to function on the dorsal wing surface. PMID- 7789264 TI - CSF-1 and mouse preimplantation development in vitro. AB - The effects of macrophage colony stimulating factor on the development of the zygote to the blastocyst stage of an outbred strain of mouse have been studied in KSOM, an improved medium that supports a high rate of in vitro development. Macrophage colony stimulating factor accelerates the formation of the blastocyst cavity by day 4 (96 hours post-hCG). It also increases overall embryonic cell number through a differential increase in the number of trophoblast cells, with no significant effect on the number of inner cell mass cells. By day 5 of culture (120 hours post-hCG), colony stimulating factor-treated embryos have about 20 more trophoblast cells than control embryos, an increase of about 30 percent of the total number of cells in a control blastocyst. The maximum response of embryos was obtained at a concentration around 540 U ml-1 colony stimulating factor (identical to 918 Stanley units ml-1), and the cytokine can produce the same effects even if it is present in the medium for only part of the culture period. This in vitro stimulation of preimplantation development with macrophage colony stimulating factor is compatible with continued normal fetal development in vivo. PMID- 7789265 TI - Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. AB - To determine if muscle sensory neurons require neurotrophin-3 (NT3) during the period of normal cell death, we used an NT3-specific antiserum to deplete NT3 from peripheral tissues during this period in chick embryos. DiI staining of dorsal roots indicated that limb injections of anti-NT3 reduced the spinal projection of muscle spindle afferents. In contrast, injection of the antiserum into the spinal cord had no demonstrable effect, indicating that the reduced projection following limb injection was due to peripheral blockade of NT3 signaling. Counts of neurons retrogradely labeled from muscle and cutaneous nerves showed that peripheral blockade of NT3 selectively reduced the survival of muscle sensory neurons without affecting the survival of cutaneous sensory neurons or motoneurons. In situ hybridization with trkC probes indicated that, during the period of cell death, most large diameter muscle sensory neurons express trkC transcripts, whereas few cutaneous neurons express this receptor for NT3. We conclude that large diameter muscle afferents, including spindle afferents, require NT3 from peripheral tissues to survive the normal period of sensory neuron death in vivo. PMID- 7789266 TI - Patterning of the mesoderm in Xenopus: dose-dependent and synergistic effects of Brachyury and Pintallavis. AB - Widespread expression of the DNA-binding protein Brachyury in Xenopus animal caps causes ectopic mesoderm formation. In this paper, we first show that two types of mesoderm are induced by different concentrations of Brachyury. Animal pole explants from embryos injected with low doses of Xbra RNA differentiate into vesicles containing mesothelial smooth muscle and mesenchyme. At higher concentrations somitic muscle is formed. The transition from smooth muscle formation to that of somitic muscle occurs over a two-fold increase in Brachyury concentration. Brachyury is required for differentiation of notochord in mouse and fish embryos, but even the highest concentrations of Brachyury do not induce this tissue in Xenopus animal caps. Co-expression of Brachyury with the secreted glycoprotein noggin does cause notochord formation, but it is difficult to understand the molecular basis of this phenomenon without knowing more about the noggin signal transduction pathway. To overcome this difficulty, we have now tested mesoderm-specific transcription factors for the ability to synergize with Brachyury. We find that co-expression of Pintallavis, but not goosecoid, with Brachyury causes formation of dorsal mesoderm, including notochord. Furthermore, the effect of Pintallavis, like that of Brachyury, is dose-dependent: a two-fold increase in Pintallavis RNA causes a transition from ventral mesoderm formation to that of muscle, and a further two-fold increase induces notochord and neural tissue. These results suggest that Pintallavis cooperates with Brachyury to pattern the mesoderm in Xenopus. PMID- 7789267 TI - Cell fate control in the Drosophila retina by the orphan receptor seven-up: its role in the decisions mediated by the ras signaling pathway. AB - Drosophila seven-up is an orphan receptor of the steroid receptor family that is required to specify photoreceptor neuron subtypes in the developing compound eye. Expression of seven-up is confined to four of the eight photoreceptor precursors, R3/R4/R1/R6. We show that misexpression of seven-up in any of the other cell types within the developing ommatidium interferes with their differentiation. Each cell type responds differently to seven-up misexpression. For example, ectopic expression in the non-neuronal cone cells using the sevenless promoter/enhancer (sev-svp) causes the cone cells to take on a neuronal identity. Ectopic expression of seven-up in R2/R5 using the rough enhancer (ro-svp) causes these neurons to lose aspects of their photoreceptor subtype identity while remaining neuronal. Each cell type appears to have a different developmental time window that is sensitive to misexpressed seven-up. The temporal order of responsiveness of each cell type to misexpressed seven-up is similar but not identical to the order of neuronal differentiation. This suggests that there are processes of specification that are distinct from the specification to become a photoreceptor neuron. We have identified members of the ras signaling pathway as suppressors of the cone cell to R7 neuron transformation caused by sev-svp. Suppression of the sev-svp phenotype can be achieved by decreasing the gene dosage of any of the members of the ras-pathway. This suggests that the function of seven-up in the cone cells requires ras signaling. However, a decrease in ras signaling results in enhancement of the phenotype caused by the ro-svp transgene. We discuss the relationship between decisions controlled by seven-up and those controlled by ras signaling. PMID- 7789268 TI - Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. AB - Hoxa 11 is a murine Abdominal-B-type homeobox gene. The structure of this gene is presented, including genomic and cDNA sequence. The cDNA includes the complete open reading frame and based on primer extension results is near full length. Surprisingly, the antisense strand of Hoxa 11 was found to be transcribed. Moreover, these antisense transcripts were processed and polyadenylated. The developmental expression patterns for both sense and antisense transcripts were examined using serial section and whole-mount in situ hybridizations. Hoxa 11 transcription patterns were defined in the limbs, kidney and stromal cells surrounding the Mullerian and Wolffian ducts. Of particular interest, in the developing limbs, the sense and antisense transcripts showed complementary expression patterns, with antisense RNAs increasing in abundance in regions where sense RNAs were diminishing in abundance. Furthermore, targeted mutation of Hoxa 11 is shown to result in both male and female sterility. The female mutants produce normal ova, which develop properly post-fertilization when transferred to wild-type surrogate mothers. The Hoxa 11 homozygous mutants are shown to provide a defective uterine environment. The mutant males exhibited a malformation of the vas deferens that resembles a partial homeotic transformation to an epididymis. In addition, the mutant testes fail to descend properly into the scrotum and, likely as a result, spermatogenesis is perturbed. PMID- 7789269 TI - Ectoderm induces muscle-specific gene expression in Drosophila embryos. AB - We have inhibited normal cell-cell interactions between mesoderm and ectoderm in wild-type Drosophila embryos, and have assayed the consequences on muscle development. Although most cells in gastrulation-arrested embryos do not differentiate, they express latent germ layer-specific genes appropriate for their position. Mesoderm cells require proximity to ectoderm to express several muscle-specific genes. We show that ventral ectoderm induces mesoderm cells to express nautilus (a MyoD homologue) and to differentiate somatic myofibers, whereas dorsal ectoderm induces mesoderm cells to express visceral and cardiac muscle-specific genes. Our findings suggest that muscle determination in Drosophila is regulated by induction between germ layers during gastrulation. PMID- 7789270 TI - Multiple roles for FGF-3 during cranial neural development in the chicken. AB - FGF-3 has been implicated in the development of the hindbrain and otocyst in vertebrate embryos. Since the chicken embryo offers a favourable system in which to study the development of these structures, we have isolated and characterised cDNAs for chicken Fgf-3 and determined its pattern of expression in chick embryos from stage 3 (primitive streak) to stage 25 (early organogenesis). Within the developing cranial neural tube, Fgf-3 exhibits dynamic spatial and temporal expression. During extension of the head process, RNA is detected in the midline of the developing neural plate. In neurulating embryos, transcripts are observed initially in rhombomeres 4 and 5 of the hindbrain and later, in rhombomere 6. During hindbrain development, expression is lost from these rhombomeres, but becomes restricted to rhombomere boundaries, providing an intracellular marker which distinguishes a population of cells within boundary regions. Fgf-3 expression is elevated in ventral and medial boundary regions and is greatly reduced in dorsal parts. Studies of regenerating rhombomere boundaries show that Fgf-3 expression is induced in reforming boundaries when even-numbered rhombomere tissue is grafted next to odd, but not when like is juxtaposed to like. Fgf-3 disappears from boundary regions just prior to the loss of the morphological boundaries suggesting a boundary-associated function. Other sites of expression have also been identified. At early stages of development Fgf-3 is expressed in the epiblast and mesendoderm of the primitive streak, in mesoderm lateral to the streak and in Hensen's node. In older embryos transcripts are detected in the endoderm of the pharyngeal pouches, the ectoderm of the second and third pharyngeal arches and the stomodeum. Expression was also detected in the segmental plate and in the posterior half of the three most-recently generated somites. PMID- 7789271 TI - The Drosophila E74 gene is required for the proper stage- and tissue-specific transcription of ecdysone-regulated genes at the onset of metamorphosis. AB - The steroid hormone ecdysone directly induces a small set of early genes, visible as puffs in the larval salivary gland polytene chromosomes, as it signals the onset of Drosophila metamorphorsis. The products of these genes appear to function as regulators that both repress their own expression and induce a large set of secondary-response late genes. We have identified recessive loss-of function mutations in the early gene E74, a member of the ets protooncogene family that encodes two related DNA-binding proteins, E74A and E74B. These mutations cause defects in pupariation and pupation, and result in lethality during metamorphosis. Here we extend our phenotypic characterization of the E74A and E74B mutant alleles to the molecular level by examining their effects on the transcription of over 30 ecdysone-regulated genes. We show that the transcription of most ecdysone primary-response genes during late larval and prepupal development is unaffected by the E74 mutations. Rather, we find that E74 is necessary for the appropriate regulation of many ecdysone secondary-response genes. E74B is required for the maximal induction of glue genes in mid third instar larval salivary glands, while E74A is required in early prepupae for the proper timing and maximal induction of a subset of late genes. E74 activity is also necessary for the correct regulation of genes expressed predominantly in the fat body, epidermis or imaginal discs. These observations confirm that E74 plays a critical role in regulating transcription during the early stages of Drosophila metamorphosis. In addition, the widespread effects of the E74 mutations on transcription indicate that E74 functions in regulatory hierarchies not only in the larval salivary gland, but throughout the entire organism. PMID- 7789272 TI - Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system. AB - The rhythmic contraction of the vertebrate heart is dependent on organized propagation of electrical excitation through the cardiac conduction system. Because both muscle- and neuron-specific genes are co-expressed in cells forming myocardial conduction tissues, two origins, myogenic and neural, have been suggested for this specialized tissue. Using replication-defective retroviruses, encoding recombinant beta-galactosidase (beta-gal), we have analyzed cell lineage for Purkinje fibers (i.e., the peripheral elements of the conduction system) in the chick heart. Functioning myocyte progenitors were virally tagged at embryonic day 3 of incubation (E3). Clonal beta-gal+ populations of cells, derived from myocytes infected at E3 were examined at 14 (E14) and 18 (E18) days of embryonic incubation. Here, we report that a subset of clonally related myocytes differentiates into conductile Purkinje fibers, invariably in close spatial association with forming coronary arterial blood vessels. These beta-gal+ myogenic clones, containing both working myocytes and Purkinje fibers, did not incorporate cells contributing to tissues of the central conduction system (e.g. atrioventricular ring and bundles). In quantitative analyses, we found that whereas the number of beta-gal+ myocyte nuclei per clone more than doubled between E14 and E18, the number of beta-gal+ Purkinje fiber nuclei remained constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789274 TI - Axonal guidance in the chicken retina. AB - During retina development, ganglion cells extend their axons exclusively into the innermost tissue layer, but not into outer retina layers. In order to elucidate guiding mechanisms for axons, tissue strips of embryonic chicken retinae were explanted onto retinal cryosections (cryoculture). Ganglion cell axons originating from the explant grew preferentially on the innermost retina layer of cryosections, whereas outer tissue layers were avoided, very much as in vivo. Stereotropism, interaction with laminin of the basal lamina and axonal fasciculation did not significantly affect oriented axonal outgrowth, so that stereotropism as a guidance mechanism could be excluded. Ganglion cell axons were not directed by physical barriers, e.g. microstructured silicon oxide chips. Similarly, UV induced protein inactivation revealed that laminin present in the inner retina did not provide a guidance cue. Even in the absence of ganglion cell axons in retinal cryosections due to prior optic nerve transection in ovo, the growth preference for the innermost retina layer was maintained in cryocultures. However, oriented elongation of axons along the innermost retina layer was lost when radial glial endfeet were selectively eliminated in retinal cryosections. In addition, glial endfeet provided an excellent growth substratum when pure preparations of endfeet were employed in explant cultures. The preference for glial endfeet positioned at the inner retina surface was accompanied by the avoidance of outer retina layers, most likely because of inhibitory components in this region. This assumption is corroborated by the finding that addition of exogenous growth-promoting laminin to cryosections did not abolish the inhibition. Laminin on glass surfaces provided an excellent substratum. Axonal outgrowth was also seriously hampered on specifically purified cells of the outer retina. Most notable, however, in cryocultures aberrant innervation of outer retina layers could be induced by prior heat or protease treatment of cryosections, which pointed to proteins as potential inhibitory components. In summary the data substantiate the hypothesis that within the retina, ganglion cell axons are guided by a dual mechanism based on a permissive and an inhibitory zone. Radial glia is likely to be instructive in this process. PMID- 7789273 TI - The role of Pax-6 in eye and nasal development. AB - Small eye (Sey) mice homozygous for mutations in the Pax-6 gene have no lenses and no nasal cavities. We have examined the ontogeny of eye and nasal defects in Sey/Sey embryos and have related the defects seen to the pattern of Pax-6 mRNA expression in the mouse during normal eye and nasal development. There are two principal components of the early eye, the neural ectoderm of the optic vesicle, which forms the retina, and the overlying surface ectoderm, which forms the lens and cornea. By studying these interacting tissues in normal and Sey/Sey embryos, we have identified processes for which Pax-6 is important and can thus suggest possible roles for the Pax-6 gene. Pax-6 is essential for the formation of lens placodes from surface ectoderm. In normal development, early Pax-6 mRNA expression in a broad domain of surface ectoderm is downregulated, but expression is specifically maintained in the developing lens placode. Moreover, other Pax-6 expressing tissues are frequently those that have can transdifferentiate into lens. Thus, phenotype and expression together suggest a role for Pax-6 in lens determination. At least some functions of Pax-6 can be separated from the influence of other tissues. Early Sey/Sey optic vesicles are abnormally broad and fail to constrict proximally. These defects occur prior to the time of lens placode formation and probably reflect a requirement for Pax-6 in neural ectoderm. In surface ectoderm domains, where Pax-6 expression is known to be independent of the presence of an optic vesicle, Pax-6 function is required for the maintenance of its own transcription. The mutual dependency of lens and optic vesicle development can also be studied using the Small eye mutation. Using region-specific markers we find that, in the morphologically abnormal Sey/Sey optic vesicles, aspects of normal proximo-distal specification nevertheless persist, despite the complete absence of lens. Like the lens, the nasal cavities develop from ectodermal placodes that normally express Pax-6 mRNA, fail to form in Sey/Sey mice and show Pax-6-dependent Pax-6 mRNA regulation. Analysis of patterns of programmed cell death and absence of nasal region expression from an Msx-1 transgene in Sey/Sey embryos suggest a requirement for Pax-6 in the transition from presumptive nasal ectoderm to placode, and that Msx-1, or genes regulating it, are possible targets for Pax-6. PMID- 7789275 TI - The Drosophila E74 gene is required for metamorphosis and plays a role in the polytene chromosome puffing response to ecdysone. AB - The steroid hormone ecdysone initiates Drosophila metamorphosis by reprogramming gene expression during late larval and prepupal development. The ecdysone inducible gene E74, a member of the ets proto-oncogene family, has been proposed to play a key role in this process. E74 is encoded within the 74EF early puff and consists of two overlapping transcription units, E74A and E74B. To assess the function(s) of E74 during metamorphosis, we have isolated and characterized recessive loss-of-function mutations specific to each transcription unit. We find that mutations in E74A and E74B are predominantly lethal during prepupal and pupal development, consistent with a critical role for their gene products in metamorphosis. Phenotypic analysis reveals that E74 function is required for both pupariation and pupation, and for the metamorphosis of both larval and imaginal tissues. E74B mutants are defective in puparium formation and head eversion and die as prepupae or cryptocephalic pupae, while E74A mutants pupariate normally and die either as prepupae or pharate adults. We have also investigated the effects of the E74 mutations on gene expression by examining the puffing pattern of the salivary gland polytene chromosomes in newly formed mutant prepupae. Most puffs are only modestly affected by the E74B mutation, whereas a subset of late puffs are sub-maximally induced in E74A mutant prepupae. These observations are consistent with Ashburner's proposal that early puff proteins induce the formation of late puffs, and define E74A as a regulator of late puff activity. They also demonstrate that E74 plays a wide role in reshaping the insect during metamorphosis, affecting tissues other than the salivary gland in which it was originally identified. PMID- 7789276 TI - Linkage of cardiac left-right asymmetry and dorsal-anterior development in Xenopus. AB - The left-right body axis is defined relative to the dorsal-ventral and anterior posterior body axes. Since left-right asymmetries are not randomly oriented with respect to dorsal-ventral and anterior-posterior spatial patterns, it is possible that a common mechanism determines all three axes in a coordinate manner. Two approaches were undertaken to determine whether alteration in dorsal-anterior development perturbs the left-right orientation of heart looping. Treatments known to decrease dorsal-anterior development in Xenopus laevis, UV irradiation during the first cell cycle or Xwnt-8 DNA injections into dorsal blastomeres, caused an increase in cardiac left-right reversals. The frequency of left-right reversal was correlated with the severity of dorsal-anterior perturbation and with the extent of anterior notochord regression. Injection of Xwnt-8 DNA into dorsal midline cells resulted in decreased dorsal-anterior development and a correlated increase in cardiac left-right reversals. In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and dorsal-anterior development and notochord formation were normal. Disrupting development of dorsal-anterior cells, including cells that give rise to the Organizer region and the notochord, results in the randomization of cardiac left-right asymmetry. These results suggest dorsal-anterior development and the regulation of left-right orientation are linked. PMID- 7789277 TI - Role of MAP kinase in mesoderm induction and axial patterning during Xenopus development. AB - We have examined the role of MAP kinase during mesoderm induction and axial patterning in Xenopus embryos. MAP Kinase Phosphatase (MKP-1) was used to inactivate endogenous MAP kinase and was found to prevent the induction of early and late mesodermal markers by both FGF and activin. In whole embryos, MKP-1 was found to disrupt posterior axial patterning, generating a phenotype similar to that obtained with a dominant inhibitory FGF receptor. Overexpression of either constitutively active MAP kinase or constitutively active MAP kinase (MEK) was sufficient to induce Xbra expression, while only constitutively active MEK was able to significantly induce expression of muscle actin. When MAP kinase phosphorylation was used as a sensitive marker of FGF receptor activity in vivo, this activity was found to persist at a low and relatively uniform level throughout blastula stage embryos. The finding that a low level of MAP kinase phosphorylation exists in unstimulated animal caps and is absent in caps overexpressing a dominant inhibitory FGF receptor provides a basis for our previous observation that overexpression of this receptor inhibits activin induction. These results indicate that FGF-dependent MAP kinase activity plays a critical role in establishing the responsiveness of embryonic tissues to mesoderm inducers. PMID- 7789278 TI - Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. AB - Mouse primordial germ cells express tissue non-specific alkaline phosphatase (TNAP) during development, but the widespread expression of another alkaline phosphatase gene in the early embryo limits the potential use of this marker to trace germ cells. To attempt to identify germ cells at all stages during embryonic development and to understand the role of TNAP in germ cell ontogeny, mice carrying a beta geo (lacZ/neor) disrupted allele of the TNAP gene were generated by homologous recombination in embryonic stem cells. Using beta galactosidase activity, the embryonic pattern of TNAP expression was examined from the blastocyst stage to embryonic day 14. Results indicate that primordial germ cell progenitors do not express TNAP prior to gastrulation although at earlier times TNAP expression is found in an extraembryonic lineage destined to form the chorion. In homozygous mutants, primordial germ cells appear unaffected indicating that TNAP is not essential for their development or migration. PMID- 7789279 TI - Autonomous and non-autonomous differentiation of ectoderm in different sea urchin species. AB - During early embryogenesis, the highly regulative sea urchin embryo relies extensively on cell-cell interactions for cellular specification. Here, the role of cellular interactions in the temporal and spatial expression of markers for oral and aboral ectoderm in Strongylocentrotus purpuratus and Lytechinus pictus was investigated. When pairs of mesomeres or animal caps, which are fated to give rise to ectoderm, were isolated and cultured they developed into ciliated embryoids that were morphologically polarized. In animal explants from S. purpuratus, the aboral ectoderm-specific Spec1 gene was activated at the same time as in control embryos and at relatively high levels. The Spec1 protein was restricted to the squamous epithelial cells in the embryoids suggesting that an oral-aboral axis formed and aboral ectoderm differentiation occurred correctly. However, the Ecto V protein, a marker for oral ectoderm differentiation, was detected throughout the embryoid and no stomodeum or ciliary band formed. These results indicated that animal explants from S. purpuratus were autonomous in their ability to form an oral-aboral axis and to differentiate aboral ectoderm, but other aspects of ectoderm differentiation require interaction with vegetal blastomeres. In contrast to S. purpuratus, aboral ectoderm-specific genes were not expressed in animal explants from L. pictus even though the resulting embryoids were morphologically very similar to those of S. purpuratus. Recombination of the explants with vegetal blastomeres or exposure to the vegetalizing agent LiCl restored activity of aboral ectoderm-specific genes, suggesting the requirement of a vegetal induction for differentiation of aboral ectoderm cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789280 TI - Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development. AB - Kidney epithelia have separate origins; collecting ducts develop by ureteric bud growth and arborisation, nephrons by induced mesenchyme-epithelium transition. Both express sulphated glycosaminoglycans (GAGs) which are strikingly upregulated during nephron differentiation. However, sodium chlorate, an inhibitor of GAG sulphation, and the GAG-degrading enzymes heparitinase plus chondroitinase, did not prevent nephron development. In contrast, ureteric bud growth and branching were reversibly inhibited by the above reagents, the inhibition correlating quantitatively with sulphated GAG deprivation caused by a range of chlorate concentrations. Growth and branching could be independently restored during GAG deprivation by hepatocyte growth factor and phorbol-12-myristate acetate (PMA) respectively. Together these signalling effectors stimulated both branch initiation and growth. Thus growth and morphogenesis of ureteric bud involve distinct signalling pathways both regulated by GAGs. PMID- 7789281 TI - Arabidopsis gynoecium structure in the wild and in ettin mutants. AB - The gynoecium is the female reproductive structure of flowering plants. Here we present a description of the Arabidopsis thaliana gynoecium at anthesis. The cylindrical organ can be broken down into three longitudinal regions arranged in an apical-basal order: stigma, style, and ovary. Each region can be distinguished histologically and morphologically. The transmitting (pollination) tract is axially positioned along the center of the gynoecium and spans stigma, style and ovary. Histochemistry, scanning electron microscopy and a style-specific reporter gene are used to compare the wild-type pattern of gynoecium cell types and regions, with patterns formed in gynoecia of individuals homozygous for a series of allelic mutations at the ETTIN locus. ettin gynoecia show morphological and histological alterations that appear to result from the merging of apical and basal regions and the development of abaxial into adaxial tissues. These developmental abnormalities result in a reduction of the ovary region, an expansion of the stylar and stigmatic regions, and the abaxial (outward) proliferation of transmitting tract tissue. The alterations in the mutants can be interpreted as resulting from misspecifications of position along the longitudinal and transverse axes during gynoecium development. The results suggest that early patterning events underlie wild-type gynoecium development, and that ETT functions during this early programming. PMID- 7789282 TI - Notch1 is required for the coordinate segmentation of somites. AB - Members of the Notch family of transmembrane receptors mediate a number of developmental decisions in invertebrates. In order to study Notch function in a vertebrate organism, we have mutated the Notch1 gene of the mouse. Notch1 gene function is required for embryonic survival in the second half of gestation. In the first half of gestation, we have found no effect of the mutation on the normal programs of neurogenesis, myogenesis or apoptosis. We conclude that Notch1 function is not essential for these processes, at least in early postimplantation development. However, we have found that somitogenesis is delayed and disorganized in Notch1 mutant embryos. We propose that Notch1 normally coordinates the process of somitogenesis, and we provide a model of how this might occur. PMID- 7789283 TI - Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction. AB - In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential. PMID- 7789284 TI - Adrenomedullin. Implications for hypertension research. PMID- 7789285 TI - Drug therapies for sexually transmitted diseases. Clinical and economic considerations. AB - Sexually transmitted diseases (STDs) are common, and result in immense social and economic costs. In some countries they have a major demographic impact. Because many STDs facilitate the transmission of HIV, the consequences of STDs are further increasing. At the same time, this association between STDs and HIV provides one of the ways in which drug therapy should be very cost effective. The perspective taken in this article is a societal one, and broader issues than those directly related to drug costs and benefits are discussed. However, it is the availability of drugs that has the potential to most quickly and most reliably make a major difference to overall health sector and societal costs as they relate to STDs. For those STDs for which curative therapy is available (particularly Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and Trichomonas vaginalis) there have been large decreases in prevalence in many parts of the world. In contrast, those STDs for which curative therapy is not available (particularly HIV, genital herpes and genital human papillomavirus infection) have had stable or increasing prevalence. For these latter infections, each new case increases the overall prevalence. Numerous features of STDs make clinical and economic evaluation difficult. These include the sensitive nature of the topic, the changing epidemiology and drug susceptibility of individual STDs, the fact that a large proportion of those infected are asymptomatic, difficulties in making specific diagnoses, the fact that often consequences are recognised late, sexual re-exposure and reinfection, and inadequate data on which to do clinical and economic evaluations. Furthermore, risk of acquiring an STD roughly correlates inversely with socioeconomic status, and countries or places with the highest rates of STDs may have the least ability to deal effectively with their diagnosis and management. Most of the direct and indirect costs are incurred by women, since they experience the vast majority of the complications of STDs. Many of these only become apparent years later, which makes it very hard to attribute costs and benefits to a specific episode of infection, and to its treatment. The late and indirect costs, plus the costs of prevention, are hard to quantify. That the major burden of STDs is in adolescents and young adults, socioeconomically disadvantaged groups and women has important implications, including for pharmacoeconomic studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789287 TI - Controversies in selection of epoetin dosages. Issues and answers. AB - Epoetin (recombinant human erythropoietin) is now a widely available though expensive treatment for the anaemia of chronic renal failure, and is effective in more than 95% of patients. Complications of epoetin in this context include hypertension in a third of cases, including hypertensive encephalopathy in a few, and thrombosis of shunts or vascular access devices. Fears that epoetin would cause progression of renal failure have not generally been confirmed, but hyperkalaemia may be a problem in the initial phase of treatment. Epoetin is up to twice as effective when administered subcutaneously rather than intravenously. Responding patients will normally do so within 3 months of starting epoetin. Failures to respond are usually due to iron deficiency or intercurrent disease. Other diseases associated with anaemia and an inappropriately low serum epoetin level include prematurity, the anaemia of cancer and rheumatoid arthritis. The baseline serum endogenous erythropoietin may provide a guide to response in some of these cases. Some encouraging results are being published. Situations where the serum erythropoietin levels are normal or elevated where epoetin has been employed include boosting of haematocrit presurgery as an adjunct to autologous blood donation, treatment of anaemic patients with myelodysplastic syndromes, and improvement of athletic performances. PMID- 7789288 TI - Optimal treatment of erectile failure in patients with diabetes. AB - Erectile failure, although a common problem in male diabetic patients, is one of the most neglected complications of diabetes. The availability of drugs like alprostadil (prostaglandin E1; PGE1) and papaverine for intracavernosal injection and the development of vacuum tumescence devices, while making therapy simple, have also reduced the necessity for specialised investigations. In the past 10 years, alprostadil has been shown to be the safest and the most effective of the intracavernosal self-injection treatments of erectile dysfunction. Vacuum tumescence devices are an acceptable noninvasive alternative in those who fail to achieve a satisfactory response to self-injection. Surgical techniques are being improved every day, and revascularisation procedures and prosthetic implants are available to couples in specialised centres. At present, systemic drug therapy has been largely ineffective for treatment in diabetic patients but progress is being made in this field. Whatever the option, involvement of the partner in decision making is of major importance for the treatment to be successful, and psychosexual counselling is a useful adjunct to medical or surgical therapy. PMID- 7789289 TI - Hypertension in pregnancy. Practical management recommendations. AB - Hypertension is a common and potentially serious complication of human pregnancy. It can be a marker of underlying maternal disease processes aggravated by pregnancy, or it can be directly related to the pregnancy (pre-eclampsia). It is associated with increased risks of fetal growth retardation and, if severe, can cause both maternal and fetal problems. The risks to both mother and neonate can be reduced by appropriate supervision and therapy. Close monitoring of maternal and fetal welfare will help to determine the optimum time for delivery. Maternal hypertension should be controlled with agents considered to be well tolerated in pregnancy. Following the index pregnancy, all patients with early and/or severe hypertension should be investigated for an underlying cause. Provided that there is clinical resolution of acute pregnancy-related hypertension, investigations are usually postponed until at least 3 months following delivery. PMID- 7789286 TI - Choosing the right ACE inhibitor. A guide to selection. AB - To find out if there are one or more criteria to guide selection among the ACE inhibitors for the treatment of arterial hypertension, we have reviewed the principal pharmacokinetic and pharmacodynamic aspects of the more frequently used agents of this class of antihypertensive drugs. Among the pharmacokinetic aspects that we have considered, terminal half-life, as related to the duration of the antihypertensive effect, and the route of elimination may have an impact in the clinical selection among the various ACE inhibitors. On the other hand, all the other characteristics have no pragmatic clinical relevance or may be corrected by dosage adjustment. Among the pharmacodynamic aspects, the antihypertensive efficacy of the different ACE inhibitors seems to be very similar, and some of the differences found in different studies are probably due to the population investigated and to the protocol of the study (time of blood pressure measurements, diet, drug dosage etc.). However, some differences can be found among the various ACE inhibitors when the antihypertensive efficacy is evaluated also as trough to peak ratio of blood pressure reduction. Indeed, in respect of the administration schedule of each ACE inhibitor not all the agents of this class have a trough to peak ratio above 50 to 60%, as suggested by the Food and Drug Administration of the US. According to this criterion, especially when blood pressure is measured with 24-hour noninvasive ambulatory blood pressure monitoring, some drugs such as lisinopril, enalapril and trandolapril should be preferred for their higher trough to peak ratios. Left ventricular hypertrophy is significantly reduced by antihypertensive agents, the ACE inhibitors being the most effective. Indeed, the reduction of left ventricle mass for each 1 mm Hg reduction in mean blood pressure is greater for ACE inhibitors than for other classes of antihypertensive agents. However, this effect seems more class related than characteristic of one or more among the various ACE inhibitors. Insulin resistance is elevated in hypertensive patients and it has been thought responsible for or associated with other metabolic abnormalities. ACE inhibitors seem to correct the insulin resistance of hypertensive patients, but this effect also appears to be class related more than limited to one ACE inhibitor or another. Our knowledge of this field is still limited and more studies are necessary, especially to understand the prognostic impact of insulin resistance and/or insulin resistance improvement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789290 TI - Trimetrexate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of Pneumocystis carinii pneumonia. AB - Trimetrexate is a folinic acid analogue structurally related to methotrexate, whose primary mechanism of action is believed to be inhibition of dihydrofolate reductase. This reduces the production of DNA and RNA precursors and leads to cell death. Trimetrexate is lipophilic and can passively diffuse across cell membranes including those of Pneumocystis carinii and its mammalian host. To minimise toxicity, trimetrexate must be coadministered with calcium folinate (leucovorin calcium), a reduced folate coenzyme, which is transported into, and protects, mammalian host cells but not P. carinii cells. In noncomparative trials trimetrexate was effective in the treatment of P. carinii pneumonia (PCP) in patients with AIDS who were intolerant of or refractory to cotrimoxazole (trimethoprim/sulfamethoxazole) and pentamidine treatment. In these patients, 2- to 4-week survival rates of 48 to 69% were reported. In a comparative trial in the initial therapy of PCP, trimetrexate was less effective than cotrimoxazole in moderate to severe disease as evidenced by a significantly higher failure rate. Trimetrexate was better tolerated than cotrimoxazole when used in this setting, however. Significantly fewer patients receiving trimetrexate plus calcium folinate discontinued treatment because of adverse events than did patients receiving cotrimoxazole. The most common adverse effect associated with trimetrexate is myelosuppression (neutropenia and thrombocytopenia); this is mitigated by coadministration of calcium folinate and is generally reversible upon dosage reduction or discontinuation. Other adverse effects include increases in serum aminotransferase levels, anaemia, fever, rash/pruritus, and increased alkaline phosphatase or serum creatinine levels. Further research into the use of trimetrexate, including its efficacy as prophylaxis, in combination with other agents and as an oral formulation, is needed to clearly define its role in the treatment of PCP and to identify patients most likely to benefit. Currently, trimetrexate should be considered as an alternative treatment option in immunocompromised patients with moderate to severe PCP who have not responded to or are intolerant of first-line therapy. PMID- 7789293 TI - Cumulative index: author and subject, volumes 25-40. PMID- 7789295 TI - [Specialization in epidemiology: strategy for the development of health services in Minas Gerais, Brazil, from the perspective of the single health system]. PMID- 7789294 TI - [Subject and action in public health]. PMID- 7789296 TI - [Multidisciplinary training program in the field of integral care for adolescents]. PMID- 7789297 TI - [Health reform and human resources of local health services: the case of Vargen Grande Paulista]. PMID- 7789298 TI - [Educational innovations in health personnel training in Mexico in the context of the transformations in Latin America]. PMID- 7789299 TI - [Elements for the analysis of the innovations in medical education in Mexico]. PMID- 7789300 TI - [Concept, actors, and variables of the medical job market]. PMID- 7789292 TI - Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension. AB - Since the earlier review in Drugs substantial additional data have accumulated regarding the antihypertensive efficacy of isradipine in various clinical situations, as well as data on its clinical effects in atherosclerosis. Recent therapeutic trials confirm that the efficacy of isradipine in the treatment of patients with mainly mild to moderate hypertension, when administered orally as a conventional or modified release preparation, is similar to that of titrated dosages of amlodipine, felodipine, nifedipine, diltiazem, captopril, methyldopa, metoprolol, prazosin and hydrochlorothiazide. A further decrease in blood pressure can be expected when isradipine is combined with another antihypertensive drug in patients who have not responded adequately to monotherapy. Initial studies have shown that intravenous isradipine is effective in controlling hypertension following coronary artery bypass graft surgery and that it appears useful in the treatment of intraoperative hypertension and hypertensive crisis, and in hypertensive disorders in pregnancy, when administered orally or intravenously. A large study, the Multicentre Isradipine Diuretic Atherosclerosis Study (MIDAS), was designed to compare the efficacy of isradipine and hydrochlorothiazide in reducing the rate of progression of carotid artery wall thickness, measured by B-mode ultrasound, as a surrogate for early atherosclerosis. Results indicated that wall thickness increased significantly less with isradipine than hydrochlorothiazide after 6 months of therapy. Thereafter the rate of progression remained parallel for the remainder of the 3 year trial. The confirmation of its antihypertensive efficacy, along with its favourable haemodynamic profile and reversal of left ventricular hypertrophy, minimal effect on glucose and lipid metabolism, preservation of quality of life and good tolerability, makes isradipine a suitable drug for the treatment of most patients with mild to moderate hypertension. PMID- 7789301 TI - [Health promotion and equity: a new concept for action in public health]. PMID- 7789302 TI - [Educational bases of workshops for teaching professors of the Dentistry School of the Pontificia Universidad Javeriana, Santafe de Bogota, Colombia]. PMID- 7789303 TI - Thyrotropin-releasing hormone and corticotropin-releasing hormone--what's the message? PMID- 7789304 TI - Changes in adrenal status affect hypothalamic thyrotropin-releasing hormone gene expression in parallel with corticotropin-releasing hormone. AB - Glucocorticoids are well known to influence the secretion of TSH from the anterior pituitary gland, although it is uncertain whether its site of action is on the hypothalamus, pituitary, or both. To determine whether glucocorticoids can modulate the concentration of pro-TRH gene expression in hypothalamic hypophysiotropic neurons, we measured the content of pro-TRH messenger RNA (mRNA) in the paraventricular nucleus (PVN) of adrenalectomized and corticosterone- and dexamethasone-treated rats compared to that in control populations using in situ hybridization histochemistry. Adrenalectomy resulted in the expected increase in corticotropin-releasing hormone mRNA in the PVN and was accompanied by a parallel rise in pro-TRH mRNA (68.3%; P < 0.05). Conversely, corticosterone and dexamethasone both resulted in profound reduction in corticotropin-releasing hormone mRNA in the PVN and a parallel reduction in pro-TRH mRNA (43.2% and 73.2% respectively; P < 0.05). No significant differences were observed in pro-TRH mRNA in the lateral hypothalamus in any of the groups. These data suggest that glucocorticoids can influence the concentration of pro-TRH mRNA in a cell specific manner and thereby could result in changes in the biosynthesis and release of TRH in hypophysiotropic neurons of the PVN. PMID- 7789305 TI - Expression of gonadotropin-releasing hormone (GnRH) receptor gene is altered by GnRH agonist desensitization in a manner similar to that of gonadotropin beta subunit genes in normal and castrated rat pituitary. AB - It was previously established that the administration of a potent GnRH agonist such as triptorelin (D-Trp6-GnRH) induced desensitization of pituitary gonadotropic cells, resulting in decreased expression of gonadotropin beta subunit genes and the suppression of LH and FSH synthesis and release. Binding of GnRH to the pituitary is also affected by agonist treatment. To examine the desensitizing effects of GnRH agonist on the expression of the pituitary GnRH receptor (GnRH-R) gene, male rats were given triptorelin (long-acting formulation, 300 micrograms/kg), and levels of GnRH-R messenger RNA (mRNA) were determined by Northern and dot blot hybridization to a 32P-labeled rat complementary DNA probe. Abundances of gonadotropin alpha-subunit, LH beta, and FSH beta mRNAs were examined in parallel, using appropriate probes. A rapid time dependent decrease in the level of GnRH-R mRNA was observed in rats after triptorelin administration. A minimum residual level of mRNA, in the range of 20 25% of the initial value, was attained as early as 5 h after treatment. Levels further stabilized to 25-30% after a small transient increase to 45% on day 5. A single injection was effective for at least 30 days, after which GnRH-R mRNA levels slowly returned to normal, suggesting a progressive abolition of agonist effects. A concomitant acute depletion of mRNA levels was observed for LH beta and FSH beta (50% decrease in about 48 and 3 h, respectively), whereas the alpha subunit message increased (rapidly reaching a level 1.8-fold that in control rats after 1-2 days). Castration induced a 3.8-fold elevation in the amounts of GnRH-R mRNA after 3 weeks, whereas alpha, LH beta, and FSH beta mRNAs increased by 6.2-, 7.9-, and 4.2-fold, respectively, compared to corresponding values in intact animals. Administration of the GnRH agonist readily prevented, for as long as 3 weeks, the stimulatory effects of castration on the GnRH-R mRNA and mRNAs for the beta-subunit of gonadotropins, but not for the alpha mRNA, which remained at a high level. When triptorelin was administered 3 weeks postoperatively, the castration-induced increase in LH beta and FSH beta was totally abolished, and no significant effect was noted on alpha-subunit mRNA. In conclusion, these data demonstrate that expression of the GnRH-R gene is subject to regulation and depends on GnRH stimulation, in a manner that indicates susceptibility to desensitizing action by the long-acting GnRH analog, triptorelin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789291 TI - Ceftazidime. An update of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. AB - Ceftazidime is a third generation cephalosporin antibacterial agent which, since its introduction in the early 1980s, has retained a broad spectrum of in vitro antimicrobial activity and clinical utility in serious infections. However, increasing resistance to ceftazidime and other third generation cephalosporins, particularly among Enterobacteriaceae, due to the emergence of plasmid-mediated extended spectrum beta-lactamases and the class I chromosomally mediated beta lactamases, is of concern. There is now a wealth of information on the pharmacokinetics of the drug. enabling ceftazidime to be used predictably, and with a low potential for adverse effects, in a diversity of patient populations. Overall, ceftazidime remains an effective agent for the treatment of serious infection, particularly those due to major nosocomial pathogens, and respiratory infections in patients with cystic fibrosis. Ceftazidime-containing regimens also remain an important option for the empirical therapy of febrile episodes in neutropenic patients. The tolerability profile of ceftazidime makes the drug a useful option in seriously ill patients who are at risk of developing adverse events with other antibacterial agents. Although patterns of bacterial resistance have changed in the ensuing years since its introduction, judicious use of this important agent will help maintain its present clinical utility. PMID- 7789306 TI - Regulation of glutamine:fructose-6-phosphate amidotransferase gene transcription by epidermal growth factor and glucose. AB - In preparation for the cellular proliferation stimulated by growth factors, the rate of macromolecular synthesis must be increased to allow for the enlargement of the cell that proceeds mitosis. The increased glycoprotein synthesis that follows growth factor stimulation would consume the hexosamines required for protein modification. Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting enzyme controlling the synthesis of the hexosamines used in these biosynthetic pathways. We tested the idea that growth factors might activate the transcription of the GFAT gene to increase the cellular content of this rate-limiting enzyme in hexosamine synthesis. We employed a human breast cancer cell line, MDA468 cells, which express high numbers of epidermal growth factor (EGF) receptors, to determine whether EGF could stimulate transcription of the GFAT gene. Our experiments showed that EGF stimulated the accumulation of GFAT messenger RNA (mRNA) to a level 4-fold higher than that in unstimulated cells. This accumulation could be largely accounted for by an increase in transcription, as assessed by nuclear run-on experiments. Furthermore, the GFAT mRNA was highly stable and not further stabilized by EGF. This effect of EGF on GFAT gene transcription required stimulation for 12-16 h with EGF. Interestingly, when cells were exposed to 25 mM glucose instead of 5 mM glucose, this effect of EGF was blocked. Glucose had no effect on the stability of the GFAT mRNA, implying that the effect of glucose was to antagonize the transcriptional effect of EGF on the GFAT gene. Glucosamine had an effect opposite that of glucose, in that it stimulated GFAT mRNA accumulation and had an additive effect with EGF on the accumulation of this mRNA. These results demonstrate that the GFAT gene undergoes a late transcriptional response to EGF and that the provision of high glucose concentrations to the cells blocks this EGF activation. This effect of glucose does not appear to result from its metabolism through GFAT to glucosamine. PMID- 7789307 TI - Electron microscopic visualization of insulin translocation into the cytoplasm and nuclei of intact H35 hepatoma cells using covalently linked Nanogold-insulin. AB - Insulin affects numerous metabolic processes as well as nuclear events such as gene transcription. Our previous ultrastructural and biochemical studies demonstrated insulin accumulation in nuclei of cultured and rapidly proliferating cells, and biochemical evidence suggested that insulin entered the cell cytoplasm before accumulating in the nucleus. The present study was undertaken to develop a covalently linked electron-dense insulin complex that could be used to visualize the intracellular translocation of insulin and confirm that insulin enters the cytoplasm of cells. Insulin was cross-linked to 1.4-nm diameter Nanogold particles. The complex binds to the plasma membrane insulin receptor, is biologically active, and is degraded by cellular insulin-degradative enzymes. Ultrastructural analysis after silver intensification of the gold particles confirmed that insulin internalization culminates in the translocation of some internalized insulin to the cytoplasm and nuclei. When cytoplasmic insulin degrading enzyme (IDE) activity was inhibited with 1,10-phenanthroline, an increase in the number of cytoplasmic and nuclear Nanogold-insulin particles was observed. The results of this and previous studies suggest that 1) the translocation of insulin to the cytoplasm, 2) the regulation of insulin degradation in the cytoplasm by IDE, 3) the possible interaction of insulin with cytoplasmic proteins other than IDE, and 4) the subsequent accumulation of intact insulin or insulin complexed with cytoplasmic proteins in nuclei may play a role in insulin's regulation of gene transcription and cell proliferation. PMID- 7789308 TI - Regulation of polymeric immunoglobulin A receptor messenger ribonucleic acid expression in rodent uteri: effect of sex hormones. AB - Previously we have shown that estradiol stimulates the production of secretory component, the external domain of the polymeric immunoglobulin A (IgA) receptor (pIgR) responsible for transporting IgA from tissues into secretions. In the present study, levels of pIgR messenger RNA (mRNA) in uterine tissues of rats were correlated with pIgR expression in epithelial cells and secretory component in uterine secretions. Analysis of uterine pIgR mRNA and pIgR expression in epithelial cells during the estrous cycle indicated that levels were high at proestrus and estrus and low at diestrus. When ovariectomized rats were treated with estradiol for 3 days, and pIgR mRNA was measured 4 and 12 h after the last injection, levels of uterine pIgR mRNA were significantly greater than those in saline-treated controls. High levels of pIgR were also detected in uterine epithelial cells and uterine secretions. When estradiol and progesterone were given in combination, progesterone partially reversed the effect of estradiol on pIgR mRNA levels and expression of pIgR in epithelial cells. These studies demonstrate that changes in uterine pIgR mRNA levels correlate with pIgR expression during the estrous cycle and in response to estradiol and progesterone. These findings suggest that mucosal immune responses in the reproductive tract are regulated in part by the actions of estradiol and progesterone on pIgR mRNA expression. PMID- 7789309 TI - Studies on the repression of basal transcription (silencing) by artificial and natural human thyroid hormone receptor-beta mutants. AB - Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate target gene transcription. Interestingly, in the absence of ligand, TRs also can repress basal transcription of positively regulated target genes, suggesting that unliganded TR may have a distinct role in gene regulation. In this paper, DNA binding, truncation, and natural human TR beta mutants were used in cotransfection and electrophoretic mobility shift assays to study various aspects of TR-mediated basal repression. Presently, little is known about the role(s) of natural human TR beta mutants on basal repression. These results show that: 1) TR binding to DNA likely is required for basal repression; 2) the amino terminal region of TR is not required for basal repression; 3) TR homodimer binding is not absolutely required for basal repression, as TR mutants that selectively form TR-retinoid X receptor heterodimers can mediate basal repression; and 4) TR mutants with poor T3-binding affinity likely have constitutive basal repression, even in the presence of ligand. These findings provide new insight on the mechanism of basal repression by unliganded TRs. PMID- 7789310 TI - 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. AB - The steroid hormone 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can elicit biological responses via a nongenomic pathway that involves rapid opening of the plasma membrane Ca2+ channels. There is also evidence that 1,25-(OH)2D3 influences insulin secretion in the pancreatic beta-cell, which is primarily mediated by a rapid rise in the concentration of intracellular free Ca2+ ([Ca2+]i). We employed fluorescent digital ratiometric video imaging at the single cell level to study the effects of 1,25-(OH)2D3 on [Ca2+]i in a pancreatic beta-cell line, RINr1046-38. In RIN cells equilibrated at a steady state glucose concentration (5.5 mM), 1,25-(OH)2D3 (2-20 nM) rapidly, within 5-10 sec, increased [Ca2+]i and evoked sinusoidal [Ca2+]i oscillations with a frequency of 1.87 +/- 0.13 min-1 and an amplitude of 236 +/- 3 nM (from the initial basal level of 110 +/- 2 nM). The [Ca2+]i oscillations were acutely dependent on extracellular Ca2+, but not on extracellular glucose. Further, we investigated the mechanisms of activation by 1,25-(OH)2D3 of the Ca2+ entry pathway in the plasma membrane and analyzed the relationship between 1,25-(OH)2D3-stimulated Ca2+ entry and Ca2+ release from intracellular stores. The 1,25-(OH)2D3-evoked [Ca2+]i oscillations were mediated by nonselective Ca2+ channels, which are permeable to Mn2+ and suppressed by extracellular La3+. Blockage of voltage dependent Ca2+ channels by nifedipine significantly decreased the amplitude of the oscillations. Depletion of intracellular Ca2+ stores with thapsigargin did not affect the 1,25-(OH)2D3-stimulated Ca2+ entry estimated by the Mn2+ entry and fura-2 fluorescence quench, which implies that the hormone directly activates nonselective Ca2+ channels. The 1,25-(OH)2D3-evoked increase in the background Ca2+ influx appears to generate [Ca2+]i oscillations by triggering Ca2+ release through the ryanodine receptor/Ca2+ release channel, but not through activation of the inositol 1,4,5-triphosphate receptor. Our findings are consistent with a role of the plasmalemmal vitamin D receptor coupled to the plasma membrane Ca2+ channels in mediating rapid effects of the hormone. We propose that the 1,25 (OH)2D3-mediated Ca2+ signaling pathway may be involved in the regulation of insulin secretion from the pancreatic beta-cell. PMID- 7789311 TI - Characterization of newly established testicular peritubular and prostatic stromal cell lines: potential use in the study of mesenchymal-epithelial interactions. AB - Testicular peritubular and prostatic stromal cells produce extracellular matrix elements and paracrine factors that modulate the cytodifferentiation and function of the corresponding epithelial cells. The present paper describes the establishment and characterization of five rat testicular cell lines with peritubular characteristics and one prostatic stromal cell line. Four peritubular cell lines were isolated after transfection of a mixed peritubular-Sertoli cell culture with a v-myc-containing plasmid. The same immortalization procedure applied to prostatic stromal cells yielded one cell line. An additional testicular cell line arose by spontaneous immortalization during serial subculture. Except for one testicular cell line (RTC-8T1), the morphology of all of the immortalized cell lines strongly resembled that of primary cultures of peritubular and stromal cells. Flow cytometric analysis demonstrated that all cell lines scored positive for alpha-smooth muscle isoactin and negative for cytokeratins, confirming their myofibroblast-like nature. None of the cell lines, however, stained positive for alkaline phosphatase, and androgen receptor expression was also lost. Typical Leydig cell characteristics, such as steroidogenesis, and Sertoli cell markers, such as transferrin secretion, were absent. Coculture of the cell lines with Sertoli cells resulted in the formation of tubular structures. A cell attachment assay and an enzyme-linked immunosorbent assay for fibronectin confirmed the production of extracellular matrix elements by all of the established cell lines. Media conditioned by the cell lines stimulated Sertoli cell transferrin production. The active principle was partially purified and resembled the P-MOD-S-like factors produced by primary cultures of peritubular and stromal cells. It is concluded that the immortalized cell lines have retained several of the characteristics of primary cultures of peritubular and stromal cells and may be useful for further studies on mesenchymal-epithelial interactions in testis and prostate. PMID- 7789312 TI - N-methyl-D-aspartic acid receptor messenger ribonucleic acid levels and luteinizing hormone release in immature female rats: effects of stage of pubertal development and exposure to ethanol. AB - This research was designed to determine 1) whether changes occur in the levels of N-methyl-D-aspartic acid (NMDA) receptor (NMDA-R) messenger RNA (mRNA) in the reproductive hypothalamus of female rats as they approach puberty, 2) whether NMDA-R stimulation would promote differential LH responses during the specific stages of peripubertal development, and 3) whether ethanol (ETOH), which is known to affect the NMDA-R in other brain systems, can alter NMDA-R-activated LH secretion at puberty. In the first experiment, female rats were killed at 15, 20, 25, and 34-36 days of age to determine the levels of mRNA that code for the NMDA R, specifically NMDA-R1, in the arcuate nucleus-median eminence (AN-ME) and preoptic area (POA) during pre- and peripubertal development by a ribonuclease protection assay. Results indicate that in juvenile animals, NMDA-R mRNA levels in the AN-ME increased at 25 days (P < 0.01). In the POA, the levels increased at 20 days (P < 0.05), but were unchanged at 25 days. During the peripubertal period, NMDA-R gene expression in the AN-ME did not change; however, gene expression in the POA increased (P < 0.05) during first proestrus, then declined during first estrus. In the second experiment, NMDA-R stimulation with N-methyl D,L-aspartic acid (NMA; 2.5 mg/kg) produced differential stimulatory effects on LH release depending upon the stage of pubertal development. In this regard, significant post-NMA percent increases in LH released over pre-NMA (basal) levels occurred during anestrus (46%; P < 0.01) and first proestrus (95%; P < 0.01), with nonsignificant increases of 18% and 28% during first estrus and diestrus, respectively. Finally, a 3 g/kg dose of ETOH given intragastrically 90 min before the NMA challenge blocked (P < 0.05) NMA-induced LH release during first proestrus. In conclusion, these findings demonstrate regional differences in the timing of NMDA-R gene expression in the reproductive hypothalamus during pubertal development, show differential responses of LH to NMDA-R activation during the peripubertal period, and continue to demonstrate the vulnerability of the hypothalamic-pituitary axis to the detrimental effects of ETOH at this critical time of development. PMID- 7789314 TI - Regulation of follistatin messenger ribonucleic acid in steroidogenic rat granulosa cell lines. AB - Follistatin is a 35-kilodalton monomer isolated from follicular fluid that acts on pituitary gonadotropes to suppress the production of FSH. Transfection of rat granulosa cells with specific oncogenes, such as simian virus 40 (SV40) DNA and Ha-ras oncogene, leads to their immortalization concomitant with preservation of their capacity for inducible steroidogenesis. Experiments were designed to investigate the regulation of follistatin messenger RNA (mRNA) accumulation upon stimulation with forskolin, 2-O-tetradecanol-phorbol-13-acetate (TPA), FSH, and hCG in four different granulosa cell lines. Granulosa cells were transfected with SV40 DNA alone (POGS5); with SV40 DNA and Ha-ras oncogene (POGRS1); with SV40 DNA, Ha-ras oncogene, and LH/CG receptor (GLHR15); or with FSH receptor (GFSHR17) expression plasmid. Cells were cultured to reach confluence and then stimulated for 6 or 24 h with ovine FSH (oFSH; 0.004-4 nM), hCG (9 nM), forskolin (50 microM), and TPA (50 nM), alone or in combination. In the POGS5 cell line, forskolin caused a 15-fold stimulation of follistatin mRNA after 24-h incubation. The POGRS1 cell line showed a time-dependent stimulation of follistatin gene expression induced by both forskolin (5.7-fold) and TPA (9.4-fold). In the GFSHR17 cells, forskolin, oFSH, and TPA induced an increase in follistatin mRNA. When oFSH (1.6 nM) was added to cells treated with forskolin (50 microM) or TPA (50 nM), no additional stimulation was observed. The GLHR15 cell line treated with hCG showed a 2.7-fold increase in follistatin mRNA accumulation within 6 h. Our data demonstrate that 1) follistatin mRNA is detectable and induced by forskolin and TPA in transformed granulosa cell lines that do not express the FSH or LH receptors; 2) in the GFSHR17 cell line, FSH, forskolin, and TPA caused a time- and dose-dependent regulation of the gene; and 3) follistatin gene expression is up-regulated by hCG in the GLHR15 cell line. We conclude that these transformed steroidogenic cell lines can serve as a useful model to study the regulation of follistatin gene expression, a peptide known to regulate pituitary and ovarian hormone secretion and differentiation of granulosa cells by its activin-binding action. Moreover, this gene can be regulated in immortalized granulosa cells by both the protein kinase A and protein kinase C pathways, although these cells express the large T antigen and the Ha-ras oncogenic proteins. PMID- 7789313 TI - Rapid protection of rat spermatogenic stem cells against procarbazine by treatment with a gonadotropin-releasing hormone antagonist (Nal-Glu) and an antiandrogen (flutamide). AB - GnRH antagonist (Nal-Glu) treatment combined with the antiandrogen flutamide was used to suppress rat spermatogenesis to achieve protection of spermatogonial stem cells against the anticancer drug procarbazine. Daily injections with Nal-Glu alone suppressed spermatogenesis in a dose-responsive manner. However, it was necessary to combine Nal-Glu (600 micrograms/kg.day) with flutamide at 20 mg/kg.day to decrease testicular weight in 2 weeks to less than 0.6 g, a level previously demonstrated sufficient to protect stem cells in our model system. The Nal-Glu-flutamide pretreatment suppressed serum gonadotropin levels and intratesticular testosterone levels (6% of control) and action, resulting in a reversible decrease in the number of late spermatids to 1% of control levels. When rats were given Nal-Glu-flutamide for 2 weeks before a 250 mg/kg dose of procarbazine, recovery of spermatogenesis, as measured by testis weight, testicular sperm head counts, and repopulation indexes, was significantly better than in control rats (no hormonal pretreatment). The protection achieved with Nal Glu-flutamide was better than that achieved with 2 weeks of testosterone and estradiol treatment. The present results show that Nal-Glu-flutamide protects spermatogonial stem cells against procarbazine and suggest a method of hormonal pretreatment to achieve rapid and efficient protection of spermatogenesis in humans. PMID- 7789315 TI - Retinoid X receptor alpha binds with the highest affinity to an imperfect direct repeat response element. AB - The regulation of gene expression by retinoids is mediated by two classes of receptors, retinoic acid receptors and retinoid X receptors (RXR). RXR can bind to specific target genes as homodimers, and these homodimers can activate gene expression in the presence of the ligand 9-cis-retinoic acid. A direct repeat of AGGTCA with a 1 base pair spacer (DR1) acts as a RXR homodimer response element in the presence of 9-cis-retinoic acid. However, it is not known if this represents the highest affinity binding site for the RXR homodimer. To investigate this question, we used a nonbiased strategy to isolate from a pool of random DNA those sequences that have the highest affinity for RXR alpha homodimers. The imperfect DR1 sequence 5'-GGGGTCAAAGGTCA displayed the highest in vitro binding affinity for RXR alpha homodimers. Transient transfection studies confirmed that this sequence is a more potent response element than is a perfect DR1 of either AGGTCA or GGGGTCA. The results also indicate that for RXR alpha homodimers, the receptor bound to the 5' half-site dislays different DNA binding specificity than that bound to the 3' half-site. Thus, DNA binding specificity is determined not only by the amino acid sequence of the protein but also by its protein-protein interactions and its position on the response element (5' vs. 3'). PMID- 7789316 TI - Growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed in mouse liver and placenta. AB - Two 5'-untranslated regions (5'UTRs) with distinctly different sequences, designated 5'UTR L1 and 5'UTR L2, were obtained by amplification of complementary DNA from mouse liver and placenta with primers complementary to sequences from the hormone-binding domain common to GH receptor (GHR) and GH-binding protein (GHBP) messenger RNAs (mRNAs). The presence of an open reading frame in the 5'UTR L2 and the high GC content of this sequence suggest that mRNAs containing this 5'UTR may be translated with a lower efficiency than those containing 5'UTR L1. Expression studies showed that 5'UTR L1 and 5'UTR L2 are present in GHR and GHBP mRNAs in both tissues. However, the relative expression of the two 5'UTRs differs between liver and placenta and in liver from different physiological states. The different expression patterns of the L1 and L2 5'UTRs predict that the corresponding 5'-noncoding exons of the GHR/GHBP gene are associated with different regulatory elements. The expression patterns of the 5'UTRs also indicate that there is a linkage between the 5'UTR present in GHR/GHBP gene transcripts and the alternative splicing of these transcripts to yield either GHR or GHBP mRNAs. The 5'-noncoding exon used for transcription of the GHR/GHBP gene, therefore, may be involved in regulating both the ratio of GHR to GHBP transcripts and the efficiency of translation of these transcripts. Transcription from the different 5'-noncoding exons of the GHR/GHBP gene thus may be a critical element in the regulation of the expression of GHR and GHBP and thereby in the control of the responses of different tissues to GH. PMID- 7789318 TI - The role of sodium in mediating adrenocorticotropin secretion by perifused rat anterior pituitary cells. AB - We studied the role of sodium ions in mediating basal and stimulated ACTH release from perifused rat anterior pituitary cells by exposing the cells to the sodium channel opener veratridine or the Na+/K(+)-adenosine triphosphatase inhibitor ouabain to increase the intracellular Na+ concentration or, conversely, by omitting Na+ from the perifusion medium or blocking Na+ entry into the cell with tetrodotoxin, a voltage-dependent sodium channel blocker, to decrease the intracellular Na+ concentration. Neither tetrodotoxin nor Na(+)-free medium had a significant effect on 100 nM arginine vasopressin (AVP) or 10 nM ovine corticotropin-releasing hormone (CRH)-induced ACTH secretion. Veratridine increased basal ACTH secretion by 122% (41.3 +/- 2.9 vs. 18.6 +/- 0.4 pg/min; P < 0.001), the initial spike phase of the response to AVP by 65% (0.28 +/- 0.01 vs. 0.17 +/- 0.03 ng/3 min; P < 0.005), the subsequent sustained phase to AVP by 129% (0.16 +/- 0.01 vs. 0.07 +/- 0.01 ng/7 min; P < 0.005), and the total response to CRH by 70% (0.39 +/- 0.01 vs. 0.23 +/- 0.04 ng/10 min; P < 0.05). Ouabain increased basal ACTH secretion by 39% (45.7 +/- 2.8 vs. 32.9 +/- 2.1 pg/min; P < 0.05), the initial spike phase of the response to AVP by 88% (0.32 +/- 0.02 vs. 0.17 +/- 0.01 ng/3 min; P < 0.005), the sustained phase response to AVP by 67% (0.10 +/- 0.01 vs. 0.06 +/- 0.01 ng/7 min; P < 0.05), and the total integrated response to CRH by 49% (0.88 +/- 0.09 vs. 0.59 +/- 0.03 ng/10 min; P < 0.05). However, the effects of both veratridine and ouabain on basal ACTH secretion were significantly attenuated in Ca(2+)-free EGTA-containing medium, suggesting that this effect was indirect, due to membrane depolarization and consequent influx of extracellular Ca2+. Dexamethasone (100 nM) had no effect on the ACTH response to either veratridine or ouabain. We conclude that changes in the intracellular Na+ concentration and sodium channel activity are not directly involved in AVP- or CRH-induced ACTH secretion. PMID- 7789317 TI - Differential pathways of insulin action upon the hepatitis B surface antigen gene expression and cell proliferation in human hepatoma cells. AB - We have shown previously that insulin at the physiological concentration suppresses hepatitis B surface antigen (HBsAg) gene expression in cultured human hepatoma Hep3B cells, and this suppression phenomenon is concomitant with the stimulation of cell proliferation. We have now examined whether these two distinct insulin actions on the Hep3B cells are mediated through the same or different signaling pathways. After prolonged treatment with high concentration of tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), the protein kinase C-alpha (PKC-alpha) level in the Hep3B cells was diminished and could not be detected by Western blot analysis. Under this condition, TPA treatment has no effect on the number or affinity of the insulin receptor on Hep3B cells. However, insulin-stimulated cell proliferation was completely abolished in the PKC-alpha depleted cells. In contrast, insulin still suppressed HBsAg gene expression with the same ED50 (approximately 0.5 nM) as the control cell. The induction of proto oncogene egr-1 (early-growth-regulatory-1) by insulin and TPA under similar conditions were also examined. Both insulin and TPA stimulated egr-1 gene expression up to 10-fold in the control cell, but neither of these two agents showed any effect on egr-1 gene expression in the PKC-alpha down-regulated Hep3B cells. These observations indicate that the PKC-alpha may be involved in the insulin induced egr-1 expression and cell proliferation but not in the insulin suppressed HBsAg gene expression in human hepatoma cells. PMID- 7789319 TI - Relaxin acts directly on rat mammary nipples to stimulate their growth. AB - Previously, we demonstrated that endogenous circulating relaxin promotes growth of the mammary nipples during the second half of pregnancy in the rat. The objective of this study was to determine whether relaxin acts directly on rat nipples to promote their growth. Initially, specific relaxin-binding cells were identified to assure that relaxin binds to the same cell types in the nipples of nonpregnant rats as those we previously described in pregnant rats. To examine relaxin-induced growth of the mammary nipples, 5 days after ovariectomy, 48 nonpregnant rats were assigned (12 rats/group) to 1 of the following 4 treatment groups: ovariectomized controls, estrogen treated, relaxin treated, and estrogen plus relaxin treated. Estrogen (0.05 micrograms 17 beta-estradiol) or estradiol vehicle (0.1 ml stripped corn oil) was administered sc on the dorsal side of the neck daily for the entire 10-day treatment period. Porcine relaxin (12.5 micrograms) or relaxin vehicle (0.05 ml 5% beeswax in corn oil) was administered sc at the base of the left abdominal nipple daily for the last 5 days of the 10 day treatment period. After hormone treatments, the lengths and wet weights of the left (relaxin-treated) and right (untreated) abdominal nipples were measured. There were three findings. First, the presence of specific relaxin binding in the epithelial cells of the lactiferous duct, smooth muscle cells, and skin of the nipples in nonpregnant rats was identical to the sites of specific relaxin binding in the nipples of pregnant rats. Second, relaxin-induced increases in nipple length and wet weight were mediated at least in part by the direct effects of relaxin in the nipple. Third, estrogen was not required for relaxin-induced increases in nipple length and wet weight. We conclude that relaxin stimulates the growth of rat mammary nipples at least in part through direct actions in the nipples, and that estrogen is not required for these actions. PMID- 7789320 TI - Spontaneous oscillations of intracellular calcium in single bovine parathyroid cells may be associated with the inhibition of parathyroid hormone secretion. AB - PTH secretion is tightly regulated by extracellular calcium ([Ca2+]e) and in turn regulates calcium homeostasis through its action on target tissues. We investigated the mechanism and physiological significance of intracellular calcium ([Ca2+]i) levels in relation to the secretion of PTH in single bovine parathyroid cells. [Ca2+]i was recorded using digital imaging microscopy, and secretion of PTH was correlated in the same cell using the reverse hemolytic plaque assay. In individual parathyroid cells, oscillations of [Ca2+]i were present in response to specific stimuli. Like secretory activity, response to [Ca2+]e concentrations was heterogeneous. Oscillations of [Ca2+]i occurred spontaneously in 22% of cells at inhibitory concentrations of [Ca2+]e. Oscillations were present only in high [Ca2+]e (> or = 1.8 mM) and not noted at lower concentrations of [Ca2+]e. The interval and amplitude of [Ca2+]i oscillations were 42 +/- 2 sec, and 20 +/- 1 nM (mean +/- SE), respectively. Oscillations were rapidly abolished when [Ca2+]e was removed by EGTA, and this effect was reversible. Addition of Mg2+ or polycationic antibiotics such as neomycin resulted in an [Ca2+]i spike, but oscillations were absent. Lanthanum, which blocks Ca2+ influx through calcium channels in various cells, rarely caused oscillations even in the presence of high concentrations of [Ca2+]e. To test the role of cAMP in [Ca2+]i oscillations, we added the beta-agonist isoproterenol. The addition of isoproterenol, however, did not cause oscillations. The number of cells that released PTH was significantly lower in cells with oscillations compared with cells without oscillations. We suggest that spontaneous [Ca2+]i oscillations are due to the influx of [Ca2+]e through ion channels rather than release from [Ca2+]i stores and may be a specific intracellular signal associated with inhibition of PTH secretion. PMID- 7789321 TI - Modulation of adenosine triphosphate-sensitive potassium channel and voltage dependent calcium channel by activin A in HIT-T15 cells. AB - The ATP-sensitive potassium channel (KATP channel) determines the membrane potential of pancreatic beta-cells and plays a critical role in the regulation of insulin secretion. The present study was conducted to investigate the effect of activin A, a member of the transforming growth factor-beta supergene family, on the KATP channel in HIT-T15 clonal hamster insulinoma cells. In an excised inside out patch, ATP-sensitive currents with a single channel conductance of approximately 20 picosiemens were observed. In an outside-out patch, currents with identical unitary conductance were also observed. In either case, the currents were augmented by diazoxide and blocked by glibenclamide, verifying that they were KATP channel currents. When KATP channel currents were monitored in an outside-out patch, activin A added to the bath solution inhibited KATP channel currents. Upon removal of activin A, the KATP channel currents were restored, suggesting that the inhibition was not due simply to spontaneous disappearance of channel activity (run-down). The KATP channel activity was markedly reduced after the addition of activin A and was reversed by diazoxide. Besides the inhibition of KATP channel, activin A increased, in a perforated patch, the amplitude of the inward Ba2+ current in response to a depolarizing pulse from -40 to +10 mV. Under the current clamp condition, activin A induced gradual depolarization, followed by a burst of action potentials. Activin-mediated action potentials were accompanied by an elevation of the cytoplasmic free calcium concentration. These results indicate that activin A causes depolarization of the plasma membrane by inhibiting the activity of the KATP channel. In addition, activin A directly modulates the voltage-dependent calcium channel and augments calcium entry. PMID- 7789322 TI - Histamine directly stimulates gonadotropin-releasing hormone secretion from GT1-1 cells via H1 receptors coupled to phosphoinositide hydrolysis. AB - It is unclear whether the central stimulating effect of histamine on GnRH secretion is exerted directly on GnRH neurosecretory neurons or indirectly via multisynaptic pathways, and controversy exists about the nature of the receptors involved. The current studies were undertaken to examine whether GnRH secretion from immortalized GnRH cell lines is directly regulated by histamine and, if so, to determine the identity of the receptors and the signaling pathways coupling this action. Histamine stimulated GnRH release from GT1-1 cells in a sustained and reversible manner and in a dose-dependent fashion. This effect was blocked by the selective H1 histamine receptor antagonist, mepyramine, but not by the H2 or H3 antagonists, ranitidine or thioperamide, respectively. Saturable and specific binding sites for [3H]mepyramine were demonstrated in GT1-1 cells, showing high affinity (apparent Kd, 37.8 nM) and density (apparent binding capacity, 279 fmol/mg protein) comparable to respective values in brain tissue. Competition of [3H]mepyramine binding was achieved with mepyramine at concentrations 3 orders of magnitude lower than those of ranitidine. Histamine also increased the production of inositol phosphates in GT1-1 cells in a dose- and time-dependent manner. This response was mimicked by the selective H1 receptor agonist 2-thiazolylethylamine and blocked by the H1 antagonists mepyramine, chlorpheniramine, and triprolidine. In contrast, histamine did not alter the formation of cAMP in GT1-1 cells. The present results show a direct action of histamine on immortalized GnRH neurons, suggesting that histamine may stimulate the reproductive axis by activation of H1 receptors on the surface of GnRH neurons coupled to the formation of inositol phosphates. PMID- 7789323 TI - Retinoic acid inhibits estrogen-induced uterine stromal and myometrial cell proliferation. AB - Retinoic acid, a potent natural derivative of vitamin A, influences proliferation in many cell types. However, little is known about the role of retinoic acid in estrogen-induced proliferation in normal physiological systems. In this study we sought to determine if in vivo administration of retinoic acid influences the proliferation of a normal estrogen target tissue, the immature rat uterus. The results indicate that treatment of animals with 30 mg/kg all-trans-retinoic acid for 3 days before 17 beta-estradiol (E2) administration diminishes DNA synthesis and cell division by approximately 50% in uterine stromal and myometrial cells. Luminal epithelial cell proliferation is not inhibited, indicating that the antiproliferative effects of all-trans-retinoic acid treatment are cell type specific. The inhibition is retinoid-specific and fully reversible 1 week after discontinuing all-trans-retinoic acid treatment. The inhibitory effect of all trans-retinoic acid is not due to a change in E2 receptor levels assessed by ligand binding. E2 induction of c-jun, a gene expressed primarily in myometrial cells, is unaffected in retinoid-treated animals. This is the first demonstration that retinoic acid inhibits estrogen-induced proliferation of uterine stromal and myometrial cells in a physiological setting. PMID- 7789324 TI - Differential effects of dimethylsulfoxide on steroidogenesis in mouse MA-10 and rat R2C Leydig tumor cells. AB - The effects of dimethylsulfoxide (DMSO) on steroidogenesis in MA-10 mouse Leydig tumor cells and R2C rat Leydig tumor cells were compared. MA-10 cells produce low basal levels of progesterone (as the major steroid synthesized), which increase several hundred-fold when stimulated with tropic hormone or the cAMP analog (Bu)2cAMP. R2C cells, on the other hand, constitutively produce high levels of progesterone in the absence of hormone stimulation of any kind. When incubated in the presence of 5% DMSO, MA-10 cells demonstrated an almost complete inhibition of progesterone production, whereas the synthesis of this steroid was virtually unaffected in R2C cells. The inhibition of steroid production in the MA-10 cell could not be attributed to an effect on protein synthesis, because this was unaffected by DMSO during the course of the incubations. The activity of the cholesterol side-chain cleavage enzyme was also unaffected by DMSO, as demonstrated by incubation of the cells with 22R-hydroxycholesterol. The production of cAMP in response to tropic hormone (hCG) and forskolin stimulation was significantly inhibited in MA-10 cells, but was much less affected in R2C cells in response to forskolin treatment. However, DMSO appeared to have no effect on the overall phosphorylation of proteins when tested either in a completely in vitro system or when MA-10 cell homogenates were used as a source of exogenous protein. Strikingly, DMSO treatment resulted in the highly specific inhibition of a series of 30-kilodalton mitochondrial proteins (named StAR for Steroidogenic Acute Regulatory protein), which we have recently shown to be indispensable for the production of steroids in MA-10 cells. The synthesis of these same proteins was much less affected in R2C cells. Although the mechanism of action by which DMSO inhibits steroidogenesis remains unknown, these results show that its action results in the complete cessation of synthesis of the StAR protein, which is required for the acute regulation of steroidogenesis in MA-10 cells. PMID- 7789325 TI - Photoperiod effects on neurohypophyseal and tuberoinfundibular dopamine metabolism in the male hamster. AB - Exposure of golden hamsters to a short photoperiod (< 12.5 h light/day) leads to suppression of gonadal function secondary to reduced gonadotropin and PRL secretion. PRL secretion is decreased despite a reduction of tuberoinfundibular dopaminergic activity. In the present study, the ability of photoperiod to affect tuberohypophyseal dopamine (DA) turnover was evaluated in long day (LD; 16 h of light, 8 h of darkness) and short day (SD; 8 h of light, 16 h of darkness) male hamsters. Exposure to SD led to decreases in testicular weight within 10 weeks and decreases in plasma PRL levels within 1 week. DA turnover in the neurointermediate lobe of the pituitary, as estimated by measuring the depletion of DA 60 min after tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine (250 mg/kg), was significantly elevated 1 and 4 weeks after transfer to SD, but returned by 10 weeks to the levels seen in LD animals. After 14 days of SD exposure an enhanced lactotroph sensitivity to DA was demonstrated and may also have contributed to suppression of PRL levels. Similarly to the findings of previous studies, DA turnover in the median eminence was depressed in animals housed in SD. The DA content of the anterior pituitary was not significantly affected by photoperiod. The data from this study suggest that decreases in PRL secretion associated with the transfer of hamsters from LD to SD conditions are at least in part caused by an increase in DA turnover by neurohypophyseal neurons. However, the involvement of other PRL-inhibiting or -stimulating factors in mediating the effects of photoperiod on PRL secretion cannot be ruled out. PMID- 7789326 TI - Cellular localization of estradiol-induced c-fos messenger ribonucleic acid in the rat uterus: c-fos expression and uterine cell proliferation do not correlate strictly. AB - Estrogens stimulate DNA synthesis and cell proliferation in the uterus. All major uterine cell types (luminal and glandular epithelium, stroma, and myometrium) respond to 17 beta-estradiol in the immature animal, whereas primarily epithelial cells of the uterine endometrium respond in the mature animal. Rapid activation of the c-fos protooncogene by estrogen precedes the uterine growth, suggesting that c-fos plays a role in amplifying the hormonal signal. The specific uterine cell types in which estrogen induces c-fos messenger RNA (mRNA) expression, however, have not been identified in either mature or immature animals. In this study, in situ hybridization was used to determine the cell type-specific location of mRNA encoding c-fos in the uterus. In both immature and mature castrated rats at 3 h after 17 beta-estradiol administration, c-fos expression was detected primarily in uterine luminal and glandular epithelia. Expression of c-fos returned to baseline levels by 24 h post 17 beta-estradiol treatment. There was no apparent difference in the uterine cell type-specific pattern of c-fos expression stimulated by estradiol in mature vs. immature animals. Nuclear run-on transcription assay in isolated luminal epithelial cell nuclei showed that c-fos gene transcription increased rapidly in the uterus after estradiol stimulation. Treatment of adult rats with a single injection of 16 alpha-estradiol, a short acting, nonmitogenic estrogen, induced c-fos primarily in the uterine glandular epithelia. Progesterone is known to modify the action of estrogen on the uterus by redirecting the proliferative response from epithelia to stroma. To determine if progesterone modulation of estrogen action involves shifting of c-fos expression to stromal cells, rats were treated with progesterone for 48 h and then killed 0, 3, 6, or 12 h after an estradiol injection. In situ hybridization analysis revealed that c-fos mRNA remained localized in the uterine luminal and glandular epithelia, and expression was not shifted to the stroma. Although these results support the idea that c-fos plays a role in proliferation of uterine epithelial cells, they also invite reassessment of the role played by c-fos in both epithelial and nonepithelial uterine cell types. PMID- 7789327 TI - Further evidence for a novel receptor for amino-terminal parathyroid hormone related protein on keratinocytes and squamous carcinoma cell lines. AB - PTH and PTH-related peptides (PTHrPs) interact with a common PTH/PTHrP receptor (type I), which is expressed in many tissues, including bone and kidney. Amino terminal PTH and PTHrPs also recognize receptors in several nonclassical PTH target tissues, and in some of these, the signaling mechanisms differ qualitatively from those of the classical type I receptor. In normal keratinocytes and squamous carcinoma cell lines, PTH and PTHrP stimulate a rise in intracellular calcium, but not cAMP, suggesting the existence of an alternate, type II PTH/PTHrP receptor. SqCC/Y1 squamous carcinoma cells stably expressing the type I receptor displayed sensitive intracellular cAMP responses to PTHrP and PTH, indicating that these cells express functional GS proteins and that the type I receptor is capable of signaling through adenylyl cyclase in this cell line. Therefore, the endogenous type II receptor in SqCC/Y1 cells differs from the cloned type I receptor. We next examined whether messenger RNA (mRNA) from keratinocytes and squamous cell lines could hybridize to a human type I PTH/PTHrP receptor complementary DNA [1.9 kilobases (kb)]. No type I receptor mRNA (2.3 kb) was detected in polyadenylated RNA from any of the squamous cell lines. However, squamous cell lines did express several mRNA transcripts that hybridized with the type I receptor probe, yet were smaller (1 and 1.5 kb) or larger (3.5-5 kb) than the cloned receptor mRNA. The predominant mRNA in two squamous carcinoma cell lines and normal keratinocytes was a 1-kb transcript. Northern analysis with five different region-specific probes that span the entire coding region of the human type I receptor was used to map homologous regions within each of the transcripts. Several of the transcripts identified in squamous lines are also present in polyadenylated RNA from SaOS-2 human bone cells, but a unique 1-kb transcript hybridizing to probe 2 (nucleotides 490-870) was observed only in squamous cells. The smaller 1- and 1.5-kb transcripts did not hybridize to probes corresponding to the extreme 5'- and 3'-coding regions of the type I receptor complementary DNA. Ribonuclease protection analysis employing riboprobes that correspond to the five region-specific DNA probes revealed strong RNA signals of the expected size in SaOS-2 cells, but no hybridization with squamous cell RNA. Several smaller, but minor, bands that were unique to squamous cells were observed with riboprobe 2 only, suggesting partial homology of this region with the type I receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789328 TI - The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein. AB - PTH and PTH-related protein (PTHrP) have been regarded to have positive inotropic effects on the heart as well as positive chronotropic and vasodilator effects. However, inotropy due to a direct effect of these peptides has not heretofore been distinguished from an indirect inotropic effect as a result of altered heart rate or coronary flow. The aim of this study was to determine whether PTH and PTHrP have direct inotropic effects in isolated perfused rat hearts. Three groups of hearts were studied; in all groups, hearts contracted isovolumically and were perfused with a constant coronary pressure. In the control group, heart rate, coronary flow, peak pressure (LVPmax), peak rate of rise of LV pressure (dP/dtmax), and peak intracellular calcium (measured by aequorin) all increased with PTH and PTHrP in a dose-dependent manner. When heart rate was fixed by pacing in a second group of rats, PTH and PTHrP increased coronary flow, LVPmax, and dP/dtmax significantly, indicating that inotropic actions were not mediated solely by chronotropic effects. However, when heart rate was fixed by pacing and, additionally, coronary flow was held constant (by maximal prevasodilation with nitroprusside) in a third group of rats, there was no significant effect of either PTH or PTHrP on LVPmax, dP/dtmax, or peak intracellular calcium. To demonstrate the responsiveness of this latter preparation to inotropic stimulation, the beta-adrenergic agonist, isoproterenol, increased LVPmax, dP/dtmax, and peak calcium even when heart rate was fixed and vasodilation was maximal. Thus, PTH and PTHrP are inotropic agents by virtue of their influence on coronary flow and heart rate, but not by any direct effect on contractile elements in the heart. PMID- 7789329 TI - Transient transfection of GGH3-1' cells [GH3 cells stably transfected with the gonadotropin-releasing hormone (GnRH) receptor complementary deoxyribonucleic acid] with the carboxyl-terminal of beta-adrenergic receptor kinase 1 blocks prolactin release: evidence for a role of the G protein beta gamma-subunit complex in GnRH signal transduction. AB - G proteins consist of heterotrimeric alpha-, beta-, and gamma-subunits. To assess the role of the beta gamma-subunit complex in GnRH receptor-mediated signal transduction, GGH3-1' cells were transfected with plasmids PRK5-beta ARK1 (495 689) containing complementary DNA (cDNA) of the carboxyl-terminal (Gly495-Leu689) of beta-adrenergic receptor kinase 1 (beta ARK1). GGH3-1' cells are GH3 cells that have been stably transfected with rat GnRH receptor cDNA. The carboxyl region of beta ARK1 (Gly495-Leu689) binds to the beta gamma complex and thereby inhibits its action. Twenty-four hours after stimulation, PRL release, cAMP release, and inositol phosphate (IP) production were measured in these cells and in control cells transfected with vector PRK5 cDNA alone. In cells expressing the beta ARK1-(495-689) sequence there was inhibition of basal PRL release (69.3%), cAMP release (61.2%), and IP production (75.5%) compared to cells containing vector only. When cells expressing the beta ARK1 fragment were stimulated with a GnRH analog (Buserelin; 10(-7) M), maximal responses were inhibited (66.1% for PRL release, 52.3% for cAMP release, and 79.1% for IP production). Scatchard analysis of GnRH analog binding was also performed in the two groups of transfected cells. No significant differences in Kd or receptor numbers were found between beta ARK1-(495-689)-transfected cells and control cells containing the vector alone. These data suggest a role for the beta gamma complex in mediation of cAMP release, IP production, and hormone release in response to agonist occupancy of the GnRH receptor. PMID- 7789330 TI - Tissue-specific expression of novel messenger ribonucleic acids cloned from a renin-expressing kidney tumor cell line (As4.1). AB - As4.1 cells are derived from a renin-expressing kidney tumor induced by tissue specific oncogene-mediated tumorigenesis in transgenic mice. These cells express high levels of renin messenger RNA (mRNA) and synthesize prorenin and renin; they were therefore used as a model to further investigate the molecular biology of renin-producing kidney cells by cloning and characterizing novel mRNAs expressed in these cells. One clone, designated 1.5, was randomly selected from an As4.1 complementary DNA (cDNA) library, and two other cDNA clones, designated 4.9 and 6.9, were obtained by screening the cDNA library using a strategy to identify As4.1 cell-specific mRNAs. Each clone exhibited a highly restricted tissue specific expression profile, including high level expression in As4.1 cells and low level expression in kidney. No homology was found between the sequence of the partial 1.5 and 4.9 cDNAs and sequences in Genbank. Southern blot analysis revealed that clone 4.9 is encoded by a single copy gene containing at least two separate exons. A homology search of the sequence of clone 6.9 revealed it to encode a cDNA to serum amyloid A protein; consistent with this identification, expression of 6.9 mRNA was highly induced in both kidney and liver after treatment of mice with Escherichia coli lipopolysaccharide. PMID- 7789331 TI - Role of specific response elements of the c-fos promoter and involvement of intermediate transcription factor(s) in the induction of Sertoli cell differentiation (transferrin promoter activation) by the testicular paracrine factor PModS. AB - A mesenchymal-epithelial cell interaction exists in the testis between the Sertoli cells that form the seminiferous tubule and the mesenchymal-derived peritubular myoid cells that surround the tubule. Analysis of the mesenchymal epithelial interactions between these cells revealed the local production of a mesenchymal factor, PModS. PModS modulates the differentiated functions of Sertoli cells in vitro, including stimulation of the iron-binding protein transferrin (Tf). Previous results have indicated that PModS-induced Tf gene expression involves the activation of immediate early genes. One of the immediate early genes was identified as c-fos. The importance of c-fos was demonstrated in the current study when a c-fos antisense oligonucleotide was found to inhibit the ability of PModS to induce the expression of a Tf promoter-chloramphenicol acetyltransferase (CAT) construct. The regulation of c-fos by PModS was investigated with various CAT constructs containing segments of the c-fos promoter, such as the serum response element (SRE), sis-inducible element (SIE), cAMP response element (CRE), and phorbol ester/TPA response element (TRE), transfected into cultured Sertoli cells. PModS has no effect on cAMP response element-CAT or TRE-CAT, suggesting that PModS does not act through stimulation of cAMP and protein kinase C pathways. PModS was found to activate the c-fos SRE-CAT construct and the SIE-CAT construct. A construct containing both SIE and SRE was stimulated to the same degree as either element alone. Gel mobility shift assays using nuclear extracts from PModS-stimulated Sertoli cells and a radiolabeled SRE oligonucleotide resulted in retarded mobility of a DNA-protein complex. A gel shift with a SRE oligonucleotide containing an ETS domain resulted in a unique shift only detected in PModS stimulated cells. PModS also promoted a gel shift with the SIE that is adjacent to the SRE on the c-fos promoter. The data imply that PModS can activate the c-fos promoter through the SRE and SIE. PModS caused a labeled activating protein 1 (AP1) oligonucleotide to form a DNA-protein complex, indicating activation of the c-fos gene and binding of the c-fos/jun complex. To study the downstream regulation of Sertoli cell differentiation, Tf gene expression was examined. CAT constructs containing deletion mutants of a 3 kilobase (kb) mouse Tf promoter were used. When transfected into Sertoli cells the 581-base pair Tf minimal promoter had only a slight response to PModS, but was activated by FSH. The 2.6-kb Tf promoter construct responded to PModS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789332 TI - Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. AB - Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the production of cytokines in bone or bone marrow. However, controversy remains on the role of candidate factors, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). As IL-1 and TNF have many additive and/or synergistic effects in bone, we tested the hypothesis that the simultaneous block of IL-1 and TNF is required to prevent the initial phase of rapid bone loss that follows ovariectomy (ovx). To this aim, rats were ovariectomized and treated for 2 weeks with either IL-1 receptor antagonist (IL-1ra), an inhibitor of IL-1, or TNF-binding protein (TNFbp), an inhibitor of TNF. Ovx increased bone marrow cell secretion of IL-1 and TNF and decreased the bone density of the distal femur, as measured by dual energy x-ray absorptiometry. Ovx-induced bone loss was decreased by both IL-1ra and TNFbp and completely prevented by simultaneous treatment with IL-1ra and TNFbp. Combined treatment with IL-1ra and TNFbp decreased urinary pyridinoline cross-links, a marker of bone resorption that reflects osteoclast number and osteoclast activity, whereas treatment with either inhibitor alone was less effective. Both IL-1ra and TNFbp decreased the number of osteoclasts on the endocortical surfaces and stimulated bone formation, but the two inhibitors had no additive effects on these indexes, suggesting that inhibition of osteoclastogenesis and stimulation of bone formation do not account for the additive bone-sparing effects of IL-1ra and TNFbp. These inhibitors had no effect in sham-operated rats, indicating that they specifically blocked estrogen dependent events. In conclusion, these data indicate that in the early post-ovx period, IL-1 and TNF play a critical causal role in inducing bone loss and do so by stimulating bone resorption and inhibiting bone formation. PMID- 7789333 TI - Effect of human growth hormone and insulin on [3H]thymidine incorporation, cell cycle progression, and cyclin D expression in 3T3-F442A preadipose cells. AB - Cellular growth- and cyclin D expression-regulating activities of GH and insulin were investigated in 3T3-F442A preadipose cells under serum-free culture conditions. The present report provides evidence that the proliferative potential of 3T3-F442A cells is reduced by GH in a time- and concentration-dependent manner based on [3H]thymidine incorporation assay and cell cycle analysis. In contrast, treatment of 3T3-F442A cells with insulin resulted in cellular proliferation. The insulin-induced proliferation of 3T3-F442A cells was diminished in the presence of GH. In an effort to define biochemical events relevant to the regulatory activities of GH and insulin on the proliferation of 3T3-F442A cells, the effects of these peptides on the expression of cyclin D were studied using Western blotting. Treatment of 3T3-F442A cells with insulin led to an increase in cyclin D expression relative to that in untreated cells. The insulin-elicited expression of cyclin D was time and dose dependent. In addition, the ability of insulin to induce cyclin D expression was reduced by GH. Our experimental results indicate that proliferation of 3T3-F442A cells was regulated by GH and insulin. The regulatory effects of GH and insulin are mediated at least in part by the alternating expression of cyclin D protein. PMID- 7789334 TI - Residual bodies activate Sertoli cell interleukin-1 alpha (IL-1 alpha) release, which triggers IL-6 production by an autocrine mechanism, through the lipoxygenase pathway. AB - Interleukin-1 (IL-1) and IL-6 are produced by Sertoli cells. As IL-1 stimulates IL-6 production in some tissues, the cascade of events that results in IL-6 secretion by Sertoli cells was studied. The addition of IL-1 alpha to Sertoli cells resulted in a time-dependent increase in IL-6 secretion. Incubation of Sertoli cells with two known stimulators of IL-1 production, lipopolysaccharide (LPS) and residual bodies, resulted in a significant increase in IL-1 release into the medium several hours before IL-6 release. That IL-1 is essential for IL 6 production from Sertoli cells was established by blocking the actions of LPS and residual bodies with an anti-IL-1 alpha antibody. An increase in the release of IL-1 before IL-6 was also observed in medium obtained from staged segments of intact seminiferous tubules; IL-1 reached a maximum level at stage VIII, when mature spermatozoa are released and residual bodies are formed and phagocytosed. The secretion of IL-6 was low during this stage and then increased progressively from stage IX onward, consistent with IL-1 stimulation of IL-6. The pathway of IL 1 alpha-induced release of IL-6 was studied in the presence of agents that influence arachidonic acid release and metabolism. IL-1 alpha was found to stimulate arachidonic acid release by Sertoli cells. Furthermore, a phospholipase A2 inhibitor, aristolochic acid, significantly decreased IL-1-, LPS-, and pyrularia pubera thionin-induced IL-6 secretion from Sertoli cells. Indomethacin, a specific inhibitor of the cyclooxygenase pathway, had no significant effect on basal, but enhanced IL-1- and LPS-stimulated IL-6 production. The involvement of arachidonic acid metabolites produced in the lipoxygenase pathway on the release of IL-6 was investigated indirectly, using nordihydroguaiaretic acid. This inhibitor reduced basal and IL-1 alpha- and LPS-stimulated IL-6 production. Ethacrynic acid, an inhibitor of peptido-leukotriene synthesis, also reduced basal IL-6 levels and blocked IL-1 alpha- as well as LPS-induced IL-6 secretion. It is concluded that IL-1 produced by Sertoli cells in response to LPS or residual bodies induces IL-6 through the lipoxygenase pathway. PMID- 7789335 TI - The reduced responsiveness of cultured bovine parathyroid cells to extracellular Ca2+ is associated with marked reduction in the expression of extracellular Ca(2+)-sensing receptor messenger ribonucleic acid and protein. AB - PTH secretion from dispersed bovine parathyroid cells maintained in culture becomes progressively less responsive to changes in the extracellular Ca2+ concentration (Ca2+o) over several days. We have now investigated whether this change in secretory control is associated with alterations in the expression of the Ca2+o-sensing receptor (BoPCaR) recently cloned from bovine parathyroid, which plays a central role in Ca2+o-regulated PTH secretion. BoPCaR messenger RNA levels dropped rapidly in cultured bovine parathyroid cells, as assessed by Northern analysis, decreasing by 78% within 18 h and remaining low for at least 4 days. The level of receptor protein decreased to a comparable extent (approximately 72-82%) after 3-4 days in culture, as determined by immunocytochemistry with specific antibodies directed at the extracellular domain of the receptor. The half-time for the reduction in receptor protein (approximately 2 days) was considerably longer, however, than that for BoPCaR messenger RNA, but was comparable to that for the loss of sensitivity of PTH secretion to Ca2+o. Indeed, there was a close linear correlation between maximal suppressibility of PTH secretion and the intensity of staining for the receptor protein (r = 0.88; P = 0.004). We conclude that alterations in the expression of BoPCaR could explain much of the reduced responsiveness of cultured bovine parathyroid cells to Ca2+o. PMID- 7789336 TI - Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice. AB - Targeted tumorigenesis, using the POMC gene promoter ligated to the simian virus 40 large T antigen, generated transgenic mice with massive tumors of the intermediate lobe (IL) of the pituitary. Inoculation of nude mice with the IL tumor cells resulted in very large secondary tumors. As the IL from several species produces a potent PRL-releasing factor (PRF), it was of interest to determine whether IL tumors from these mice also contain PRF. The objectives were to 1) measure serum PRL levels in mice with IL tumors, 2) determine whether these tumors contain PRF and examine its chromatographic properties, and 3) analyze whether this PRF is related to POMC, its derivatives, or other PRL secretagogues. Serum PRL levels were 5- to 6-fold higher in transgenic than in control mice. Primary and secondary IL tumors were acid extracted and successively fractionated using Sephadex G-100 gel filtration and reverse phase and gel permeation HPLC. PRF activity was determined using short term incubation of tissue extracts or column fractions with GH3 cells. Crude tumor extracts exhibited a strong and dose dependent PRF activity. Upon chromatography, the PRF activity from either primary or secondary tumors resolved into two classes of compounds: a big PRF with an estimated mol wt of 70-80 kilodaltons and two small, very hydrophobic peptides. The elution profiles of the three PRFs differed from those of beta-endorphin, alpha MSH, beta MSH, ACTH, TRH, oxytocin, angiotensin II, vasoactive intestinal polypeptide, or corticotropin-like intermediate peptide. In summary, we have identified an animal model with IL tumors that has hyperprolactinemia and overproduces PRF. Two classes of PRFs, big and small, were resolved which differ from POMC derivatives and known regulators of PRL release. These data suggest that PRF is produced by melanotrophs, but is not a product of the POMC gene. The IL tumors should provide an excellent source for the purification and structural elucidation of PRFs. PMID- 7789337 TI - Combined magnetic fields increase insulin-like growth factor-II in TE-85 human osteosarcoma bone cell cultures. AB - In vitro exposure to low-energy, combined magnetic fields (CMF) increased the release of insulin-like growth factor (IGF)-II from human TE-85 osteosarcoma cells. Short-term CMF exposure of only 10 min increased IGF-II levels in conditioned medium 1 h post CMF exposure. IGF-II levels were measured with a radioreceptor assay using H-35 cells that contain abundant IGF-II but not IGF-I receptors. This assay also uses a recently validated BioGel P-10 acid gel filtration method to remove IGF binding protein before quantitation of either IGF I or IGF-II. In addition to an increase in IGF-II levels, DNA synthesis, as an index of cell proliferation, was increased during the 24-h period post CMF exposure. A monoclonal antibody against IGF-II blocked the increase in cell proliferation following CMF exposure, whereas a control monoclonal antibody against osteocalcin did not attenuate the mitogenic action of CMF exposure. The effect of CMF exposure to increase both cell proliferation and IGF-II was cell density dependent with greater stimulation by CMF observed at lower densities. Together, these data are consistent with the hypothesis that CMF exposure stimulates release/production of IGF-II from bone cells and that increased IGF-II then promotes an increase in cell proliferation. PMID- 7789338 TI - Glucocorticoid and/or glucocorticoid antagonist effects in inflammatory disease susceptible Lewis rats and inflammatory disease-resistant Fischer rats. AB - Lewis (LEW/N) and Fischer (F344) rats are inbred strains that respond antithetically to administration of several inflammatory stimuli. Thus, in response to streptococcal cell wall-derived peptidoglycan/polysaccharide, 6-week old female Lewis rats develop acute and chronic polyarthritis, whereas age- and sex-matched Fischer rats are arthritis-resistant. The susceptibility of Lewis rats to development of chronic severe inflammatory disease has been attributed to their inability to appropriately activate their hypothalamic-pituitary-adrenal axis in response to inflammatory stimuli, leading to a functional glucocorticoid deficiency. To investigate whether the acute neurogenic inflammatory response was also different in the two strains, we studied the air-pouch model of carrageenin induced neurogenic inflammation in adult male Lewis and Fischer rats. Both the volume and the leukocyte concentration of the inflammatory exudate were significantly higher in Lewis than in Fischer rats, suggesting that the known differences in the handling of chronic inflammation between the two strains pertain to the acute neurogenic type of inflammation as well. To confirm that glucocorticoids play a major role in the differential response of the two strains to this inflammatory stimulus, we administered graded doses of the glucocorticoid agonist dexamethasone or antagonist RU 486 to both strains and examined their responses to concomitantly administered carrageenin. RU 486 increased, whereas dexamethasone decreased, the inflammatory response of Fischer and Lewis rats, respectively, to approach the magnitude of each other's natural response, suggesting that glucocorticoids are involved in this phenomenon as well. To rule out any differences in end-organ sensitivity to glucocorticoids between the two strains, we evaluated dose-response relations of whole body, thymus, spleen, and adrenal weights after 1 week daily administration of graded doses of dexamethasone. We found similar ED50 for both Lewis and Fischer rats. We conclude that the differences in the susceptibility to acute, carrageenin-induced, neurogenic inflammation between the LEW/N and F344 rat strains are similar to those of chronic inflammatory responses in these strains and likewise glucocorticoid-dependent. No apparent major differences exist in the sensitivity of target tissues to exogenous glucocorticoids between Lewis and Fischer rats. PMID- 7789339 TI - Regulation of the cell-cell adhesion protein, E-cadherin, in dog and human thyrocytes in vitro. AB - E-cadherin, a cell-cell adhesion protein specifically expressed at the basolateral membrane of thyrocytes, is variably dysregulated in thyroid carcinomas in parallel to the dedifferentiation of the tumors. No data are currently available on the regulation of E-cadherin in messenger RNA (mRNA) expression by physiological stimulators of thyroid proliferation and differentiation. The present study investigated the control of E-cadherin steady state mRNA levels and protein expression in primary cultures of dog and human thyrocytes under the influence of physiological regulators of thyroid differentiation and dedifferentiation using Northern blot analysis and immunohistochemistry. Following dedifferentiation by epidermal growth factor and fetal calf serum in primary cultures of dog and human thyrocytes, E-cadherin steady state mRNA expression was low but easily detectable. Stimulation of the cells by TSH (1 mU/ml) or forskolin (10 microM) induced an increase in E-cadherin mRNA levels with a maximal effect after 20 h. An up-regulation of E-cadherin protein levels are also observed by immunostaining with anti-E-cadherin antibodies. A concentration-response relation determined for TSH stimulation (10 microU/ml to 10 mU/ml) led to a concentration-dependent stimulation of E-cadherin mRNA levels and a parallel increase in protein expression with a minimal effective concentration of 10-30 microU/ml. These effects depend on protein synthesis as they are completely blocked by the presence of 10 micrograms/ml cycloheximide. Treatment with EGF did not markedly alter E-cadherin mRNA expression, whereas removal of insulin from the medium slightly decreased E cadherin mRNA and protein levels. There is, therefore, a qualitative parallelism between the effect of the various factors on E-cadherin protein and mRNA levels. These results suggest that the cell-cell adhesion protein E-cadherin is under the control of the TSH-cAMP-dependent pathway and may play an important physiological role on the action of this pathway in proliferation and differentiation. PMID- 7789340 TI - Activation of the Na+/H+ exchanger by cellular pH and extracellular Na+ in rat adipocytes; inhibition by isoproterenol. AB - The activity of the Na+/H+ exchanger was studied by measuring the effects of intracellular pH (pHi) and extracellular Na+ [(Na+)o] on pHi recovery and 22Na uptake in rat adipocytes. The resting pHi was acidified from 7.30 +/- 0.02 to 6.99 +/- 0.01 with nigericin in the absence of (Na+)o. pHi recovery induced by 30 mM NaCl was blocked by 100 microM amiloride. The reversibility of the exchanger was studied by Na+ loading, which raised the pHi from 7.30 +/- 0.02 to 7.50 +/- 0.01, and by removing (Na+)o, which decreased pHi to 6.97 +/- 0.01. Both functions of the exchanger, forward and backward, were inhibited by amiloride. The Na+/H+ exchanger was inactive at pHi higher than 7.1 and became increasingly active as pHi decreased to 6.2 (22Na+ uptake, 0.029 +/- 0.003 vs. 0.155 +/- 0.009 nmol/10(5) cells.2.5 min; P < 0.001); this 5-fold stimulation was largely abolished by amiloride (0.025 +/- 0.002; P < 0.001). Na+ influx was also increased as a function of (Na+)o, with an apparent Km of 35 mM. Respective 5- and 44-fold stimulations at 5 mM (0.135 +/- 0.007) and 140 mM (Na+)o (1.228 +/- 0.046 nmol/10(5) cells.2.5 min; P < 0.001) were inhibited by ethylisopropylamiloride. Isoproterenol (Iso; 100 nM) and agents that stimulate cAMP production, such as forskolin (10 microM) and theophyline (1 mM), inhibited the activity of amiloride-sensitive 22Na+ uptake by 85%. Iso inhibited the Na+/H+ exchanger, without affecting the Na+/K(+)-adenosine triphosphatase-dependent and the Na+/K+/Cl- cotransport mechanisms. (Bu)2cAMP (1 mM), a membrane-permeant cAMP analog, mimicked the effects of Iso on the exchanger. The inhibitory effect of Iso was blocked by propranolol, but not by metoprolol, a beta 1-antagonist. In addition, the alpha-adrenergic agonists, phenylephrine (alpha 1) and clonidine (alpha 2), and the alpha-antagonists, prazocin (alpha 1) and yohimbine (alpha 2), did not prevent Iso-induced inhibition of the exchanger. In conclusion, rat adipocytes possess a reversible Na+/H+ exchange mechanism, which is activated by low pHi and normal (Na+)o and is inhibited by Iso via a beta 2-adrenergic receptor stimulation and a cAMP-dependent mechanism. PMID- 7789341 TI - Alternative splicing and differential targeting of fibroblast growth factor receptor 1 in the pregnant rat uterus. AB - Recent studies suggest that steroid effects on uterine cell proliferation may be moderated by polypeptide growth factors. We now provide evidence that high affinity fibroblast growth factor (FGF) receptors are present temporally and spatially in the pregnant rat uterus (days 4-6) to support the idea that basic FGF action occurs via binding to its high affinity FGF receptor 1 (FGFR1). Reverse transcription-polymerase chain amplification indicates that both the full length transcript and an alternatively spliced messenger RNA are present in the uterus. Western immunoblot analysis confirms that rat uterine membrane proteins contain two receptor isoforms, and these receptors bind basic FGF with high affinity and specificity. Immunolocalization of FGFR1 revealed receptor-positive cells in both the uterine stroma and epithelia on days 4-6 of pregnancy. However, the receptor was differentially localized in the disparate cell types. The nuclei of stromal cells were positive for FGFR1, whereas epithelial cell nuclei were negative. Together, these results suggest that FGF signal transduction in uterine stromal cells is mediated by activation of FGFR1. PMID- 7789342 TI - The thyrotropin (TSH) receptor transmembrane domain mutation (Pro556-Leu) in the hypothyroid hyt/hyt mouse results in plasma membrane targeting but defective TSH binding. AB - The hyt/hyt mouse is hypothyroid because of a mutation in the TSH receptor (TSH R). In this report, we confirm the presence of a Pro to Leu mutation in amino acid 556 of the fourth transmembrane domain (TM4) of the TSH-R. This Pro is highly conserved in members of the G protein-coupled seven-transmembrane family of receptors. Insertion of this mutation into the wild-type rat receptor eliminated TSH binding and receptor function in transfected 293 and COS cells. Wild-type TSH-R conferred a 7.4-fold increase in cAMP and a 2.3-fold stimulation of a cAMP-responsive reporter gene. The P556L mutant receptor elicited no increase in cAMP or the reporter gene. Cells transfected with wild-type receptor bound TSH with a Kd of 3.3 x 10(-10) M, whereas no TSH binding was detected with the P556L mutant. Because the P556L mutation occurs in a receptor region (TM4) that is not expected to alter the binding of TSH, additional studies were performed to examine receptor processing and cellular localization. Mutant receptors from solubilized membranes also failed to bind TSH, indicating that the absence of binding to intact cells was not accounted for intracellular trapping of the mutant receptor. Western blot analyses demonstrated that the mutant and wild-type receptors were processed through a similar series of precursors and that a mature 95-kilodalton form of the mutant TSH-R was produced, consistent with its insertion into the plasma membrane. Immunofluorescence studies confirmed expression of the P556L mutant on the cell surface of transfected cells and in thyroid tissue from hyt/hyt mice. Although the extracellular domain of the TSH-R is sufficient for high affinity binding of TSH, we conclude that the hyt mutation in the fourth transmembrane domain eliminates TSH binding. These results suggest interactions between the extracellular and transmembrane domains of the TSH-R and indicate that this highly conserved proline is required for normal receptor structure and function. PMID- 7789343 TI - Presence of nerve growth factor and its receptors in an in vitro model of islet cell development: implication in normal islet morphogenesis. AB - In vivo, the differentiation of pancreatic islet stem cells depends on unknown soluble factors produced by the mesenchyme surrounding these cells. We have previously demonstrated that, like some neuronal cells, different beta-cell lines express functional nerve growth factor (NGF) receptors and can respond to NGF by extending neurite-like processes. NGF receptors are also expressed in vivo in mature rat islets and early during development in pancreatic ductular cells, which represent putative beta-stem cells. In this study, we have further characterized an in vitro model of islet development and studied the expression of NGF receptors and its ligand in this model. We have demonstrated the expression of Trk-A messenger RNA coding for the high affinity NGF receptor in islet cells and the localization of Trk protein in both alpha- and beta-islet cells. Moreover, the cells, from which islet cells "bud," also express Trk-A. Furthermore, NGF is produced and secreted by the nonendocrine cells surrounding the islets, suggesting a possible paracrine mode of action of NGF on the adjacent islet cells. Finally, islet morphogenesis is significantly retarded in the presence of K252a, an inhibitor of the tyrosine kinase activity of the family of Trk receptors, suggesting an implication of the neurotrophin-neurotrophin receptor axis in islet development. PMID- 7789344 TI - Effects of psychosocial interventions with adult cancer patients: a meta-analysis of randomized experiments. AB - Meta-analytic methods were used to synthesize the results of published randomized, controlled-outcome studies of psychosocial interventions with adult cancer patients. Forty-five studies reporting 62 treatment-control comparisons were identified. Samples were predominantly White, female, and from the United States. Beneficial effect size ds were .24 for emotional adjustment measures, .19 for functional adjustment measures, .26 for measures of treatment- and disease related symptoms, and .28 for compound and global measures. The effect size of .17 found for medical measures was not statistically significant for the few reporting studies. Effect sizes for treatment-control comparisons did not significantly differ among several categories of treatment: behavioral interventions, nonbehavioral counseling and therapy, informational and educational methods, organized social support provided by other patients, and other nonhospice interventions. PMID- 7789345 TI - Effects of decreasing sedentary behavior and increasing activity on weight change in obese children. AB - Obese children 8-12 years old from 61 families were randomized to treatment groups that targeted increased exercise, decreased sedentary behaviors, or both (combined group) to test the influence of reinforcing children to be more active or less sedentary on child weight change. Significant decreases in percentage overweight were observed after 4 months between the sedentary and the exercise groups (-19.9 vs. -13.2). At 1 year, the sedentary group had a greater decrease in percentage overweight than did the combined and the exercise groups (-18.7 vs. -10.3 and -8.7) and greater decrease in percentage of body fat (-4.7 vs. -1.3). All groups improved fitness during treatment and follow-up. Children in the sedentary group increased their liking for high-intensity activity and reported lower caloric intake than did children in the exercise group. These results support the goal of reducing time spent in sedentary activities to improve weight loss. PMID- 7789346 TI - Relationship between obesity and the metabolic effects of smoking in women. AB - The influence of cigarette smoking on resting energy expenditure (REE) in normal weight and obese smokers was investigated. Participants were 20 normal-weight and 20 obese female smokers assessed over a 2-day period. The results indicated that REE increased in both obese and normal-weight smokers after smoking, but the increase was greater for normal-weight participants. The normal-weight group showed a 9.7%, 5.8%, and a 3.6% increase in REE during the three 10-min blocks constituting the 30-min postsmoking phase. However, the obese group showed a 3.9% and a 0.7% increase in REE and a 0.8% decrease in REE during this postsmoking phase. Between-group comparisons revealed a differential rate of change in REE after smoking, indicating that the obese group's change of REE at every postsmoking time point was on average 70 kcal/day below that of the normal-weight group. The metabolic effect of smoking is reproducible, and the obese smokers reliably show an attenuated effect. However, the reliability of the change is lower for both normal-weight and obese smokers. The results have potential implications for discouraging obese persons from taking up smoking and intervening among those who already smoke. PMID- 7789347 TI - The effect of smoking and light activity on metabolism in men. AB - This experiment examined the metabolic effects of smoking during rest and light activity under naturalistic conditions. Thirty-nine male subjects first completed a submaximal graded exercise treadmill test to standardize activity level. Then 3 groups of subjects--smokers smoking (SS), smokers not smoking (SNS), and nonsmokers (NS)--were exposed to 3 stages of rest or 3 stages of light activity with order of rest or activity randomly determined over 2 different days. Energy expenditure was monitored continuously during these sessions. Significant increases in smokers' energy expenditure were observed during light activity when compared with smokers not smoking and nonsmokers. No differences were identified among groups at rest. These findings strengthen the conclusion that smoking or its components contribute to metabolic changes during typical levels of daily activity and suggest a mechanism for the frequently observed relationship between smoking status and body weight. PMID- 7789348 TI - Resistance of personal risk perceptions to debiasing interventions. AB - The tendency to believe that one's own risk is less than that of others may reduce interest in health-protective behaviors. This article describes 4 attempts to reduce such optimistic biases. In Study 1, New Jersey residents (N = 222) were provided with lists of risk factors for several health problems. This manipulation was strengthened in Study 2 by presenting risk factors in such a way that participants (164 undergraduates) might see their own standing as inferior to that of others. In Study 3, risk factors were presented one at a time, and participants (190 undergraduates) incorporated them into a mental image of a high risk individual. Finally, 374 undergraduates in Study 4 generated lists of personal attributes that they believed increased their risk. Optimistic biases were found in each study, but none of the manipulations reduced these biases consistently. In contrast, conditions using opposite manipulations often exacerbated the biases. PMID- 7789349 TI - Negative affective consequences of thinking about disease detection behaviors. AB - It was proposed that thinking about disease-detection behavior would lead to more negative moods than thinking about health-promotion behavior. Detection behaviors produce more negative moods because they can threaten perceptions of good health. In a laboratory study, the initial mood states of 121 participants recruited from undergraduates and the general community were measured using a neutral-words rating procedure. Then participants were randomly assigned to think about performing a disease-detection behavior or a health-promotion behavior. Subsequently, they wrote down their responses to the behavior and evaluated these as either positive, negative, or neutral. Finally, the participant's mood was remeasured using both a neutral words-rating procedure and a more traditional bipolar rating measure. Results indicated that thought about disease-detection behavior produced more negative affective responses and more negative mood change than did thought about health-promotion behavior. PMID- 7789350 TI - Magical thinking about illness virulence: conceptions of germs from "safe" versus "dangerous" others. AB - AIDS-related research has documented overreactions to casual contact and underreactions to sexual risk. This contradiction is explained by "magical contagion", a principle of thinking common in traditional societies, wherein contagion is considered socially discriminating, such that harmfulness depends on the nature of the relationship between source and recipient. In Study 1, 100 undergraduate participants drew germs described as their own, a stranger's, their lover's, or a disliked peer's. Lovers' germs were depicted as less threatening than disliked peers' germs. In Study 2, scenarios described contact with a flu infected lover, stranger, or disliked peer. New undergraduate participants (N = 133) rated how likely they were to become ill and how severely. Although likelihood ratings did not differ, severity ratings followed a linear trend, effects of lover contact being least severe and contact with disliked peer most severe. Behavioral implications of the blurring of feelings about germ source with estimates of germ virulence are discussed. PMID- 7789352 TI - Walking to meet health guidelines: the effect of prompting frequency and prompt structure. AB - This study assessed the effects of frequency of prompting (phone calls once a week versus once every 3 weeks) and structure of prompting (high versus low structure) in 135 participants (132 women and 3 men) in a walking program designed to meet the American College of Sports Medicine's cardiovascular exercise goals. Survival analysis using 6 months of data points and using the criteria of walking at least 20 min a day for at least 3 times per week indicated an effect for more frequent versus less frequent prompting (46% and 13%) but not for high- versus low-structure prompting (30% and 31%). The results suggested the efficacy of frequent prompting delivered in inexpensive ways as a means to increase exercise adherence and the further parametric study of other basic behavior change strategies. PMID- 7789353 TI - Visual discrimination of pigmented skin lesions. AB - Three experiments explored human performance in discrimination of pigmented skin lesions from photographic slides. Experiment 1 showed that latent ability in identifying early melanoma was low, and some benign lesions tended to be falsely identified as serious. Performance overall did not decline when viewing time was reduced, suggesting that judgments could be made on the general appearance of lesions. Experiment 2 showed that enlargement of stimuli had no effect. Experiment 3 showed that performance was better with pictorial examples than with written descriptions for some classes of lesion, but for melanoma performance improved with longer viewing time when information was provided, suggesting that an opportunity to scrutinize could be beneficial. Guidelines to the public should distinguish melanoma from benign lesions and stress the importance of seeking prompt medical attention for suspicious lesions. PMID- 7789351 TI - Social support, coping, and depressive symptoms in a late-middle-aged sample of patients reporting cardiac illness. AB - This study tests a 1-year predictive model of depressive symptoms in a late middle-aged sample of patients reporting diagnoses of cardiac illness. Results based on 325 individuals (248 men and 77 women) diagnosed with chronic cardiac illness, 71 individuals (52 men and 19 women) diagnosed with acute cardiac illness, and 219 healthy controls (129 men and 90 women) strongly supported the hypotheses. Compared with healthy persons, individuals with chronic and those with acute cardiac illness reported more depressive symptoms at follow-up. Women overall showed more depressive symptoms than did men, and women with cardiac illness were particularly vulnerable to behavioral manifestations of depressive symptoms. Integrative time-lag and prospective structural equation models indicated that, for individuals with cardiac illness, social support and adaptive coping strategies predicted fewer depressive symptoms. PMID- 7789354 TI - The effects of message framing on mammography utilization. AB - This experiment compared the effectiveness of gain-versus loss-framed messages to persuade women to obtain mammography screening. One hundred and thirty-three women 40 years and older and not adhering to current guidelines for obtaining mammography screening were assigned randomly to view either gain-framed (emphasizing the benefits of obtaining mammography) or loss-framed (emphasizing the risks of not obtaining mammography) persuasive videos that were factually equivalent. Attitudes and beliefs were measured before and immediately following the intervention. Mammography utilization was assessed 6 and 12 months later. Consistent with predictions based on prospect theory, women who viewed the loss framed message were more likely to have obtained a mammogram within 12 months of the intervention. These findings suggest that loss-framed messages may have an advantage in the promotion of detection behaviors such as mammography. PMID- 7789355 TI - Behavioral research in cancer as a model for health psychology. PMID- 7789356 TI - Influence of heredity on human sensitivity to environmental chemicals. AB - Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals. PMID- 7789357 TI - Uniparental disomy and genomic imprinting as causes of human genetic disease. AB - The existence of parent-of-origin differences in the expression of some genes, a process known as genomic imprinting, has been recognized and documented over the past several years. This epigenetic marking process results in the differential expression of normal genes depending upon whether they were inherited from the mother or the father. A number of human disorders have been identified as resulting from alterations in genomic imprinting. One process which can unmask genomic imprinting is uniparental disomy, in which both members of a chromosome pair are contributed by one sex parent. When uniparental disomy is present, genetic abnormality can result either from homozygosity of a single mutant allele which is present in two doses, or from the presence of two copies of an imprinted unexpressed gene or genes, rather than the usual one expressed and one unexpressed. Examples of human genetic disorders that are the consequence of genomic imprinting, and a discussion of current knowledge about the mechanisms of imprinting and the causes of uniparental disomy, are reviewed. PMID- 7789358 TI - Mutagenesis and human genetic disease: an introduction. AB - This special issue attempts to provide a fresh perspective on the importance of germ-cell mutagenesis studies and restate the questions and challenges inherent in efforts to minimize the incidence of human genetic diseases. We are working in a time when rapidly advancing molecular technologies provide the tools that permit a more detailed understanding of germ-cell mutagenesis and genetic disease. Meanwhile, discoveries of new genetic disease phenomena challenge our abilities to conceive and develop research models for their study. It is hoped that the collection of articles in this issue will serve to stimulate interest in scientists of varied disciplines and help focus those interests on the issues surrounding the relationship between environmental mutagens and human genetic disease. PMID- 7789359 TI - Mosaicism: the embryo as a target for induction of mutations leading to cancer and genetic disease. AB - Mosaicism, the existence of "patches" of cells with a genetic constitution that differs from that of other cells of an organism, has been observed in both germinal and somatic tissues of several species, including humans. Mutational events occurring during early embryogenesis can give rise to an organism with a significant number of cells with the mutant genotype in one or more tissues. If this event occurs in a precursor of the germ cells, the mutation can be transferred to subsequent generations. In the F1 generation, this event will usually be perceived as a de novo germinal mutation rather than a transmitted variant allele, unless significant effort is directed toward detecting the mosaicism. Similarly, mutations in oncogenes and tumor-suppressor genes in proliferating somatic cells can generate populations of cells that are at increased risk of transforming into tumor cells. The number of potential preneoplastic cells is larger when the mutagenic event occurs in early development than if it occurs in the mature adult. Experimental data confirm that treatment of the developing embryo or fetus with carcinogenic and mutagenic agents increases the cancer incidence in these animals and the frequency of mutations in the offspring of the animals that were exposed in utero. The available data are conclusive that the developing organism is at risk from exposure to mutagenic and carcinogenic agents. However, the data are insufficient to estimate the level of risk associated with exposures in utero, relative to either the background (spontaneous) level of risk or risk associated with similar exposures to the adult organism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789360 TI - Mitochondrial mutations and human disease. AB - The mitochondrial genome is essential for producing ATP (adenosine 5' triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA. In both the cases of aging and disease, symptoms were generally neuromuscular, reflecting the tissues most dependent upon mitochondrial function. Also, in both cases novel features of mitochondrial genetics led to complex relations between genotype and phenotype. Little information is yet available about the role of environmental agents in these interactions. PMID- 7789361 TI - Etiology of nondisjunction in humans. AB - Aneuploidy is the most common class of chromosome abnormality in humans, occurring in at least 0.3% of newborns and approximately 50% of spontaneous abortions. Considered as a class, it is the most common known cause of mental retardation and the leading cause of pregnancy loss. Despite the high frequency of aneuploidy, its obvious clinical importance, its severe impact on human reproduction, and the 35 years of research since the first human chromosome abnormality was described, we still know very little about its causes, let alone the contribution of environmental exposures. Recently, however, with the advent of molecular and molecular cytogenetic techniques and advances in reproductive biology, a body of evidence has been generated that is beginning to shed light on the incidence, origin, and etiology of human aneuploid conditions. The bulk of this evidence comes from two sources: 1) studies of the incidence of aneuploidy in the cells of origin, namely oocytes and sperm; and 2) examinations of meiotic stage, parent of origin, and meiotic recombination in trisomic conceptuses, both liveborn and abortuses. Using a multicolor fluorescence in situ hybridization (FISH) approach, it is now possible to screen on extremely large number of human sperm to determine chromosome-specific rates of disomy. Likewise, because of the introduction in the past decade of in vitro fertilization technology, a population of human oocytes suitable for aneuploidy screening became available. The examination of the cells of origin of aneuploidy, the sperm and oocytes, has provided data on the incidence of chromosome aberrations and valuable insight into possible mechanisms of nondisjunction. Additionally, the recent identification of multiple, highly informative DNA polymorphisms on all human chromosomes has made the determination of parental origin and the analysis of recombination a straightforward matter. We now know that the vast majority of trisomic conceptuses are maternal in origin, that increased maternal age is associated with nondisjunction, and that the amount and position of recombination on nondisjoined chromosomes is altered. In this review we will restrict discussions to these recent developments and to new models of the mechanism(s) of human nondisjunction based on the molecular cytogenetic analyses. Additionally, we will discuss the direction of future epidemiological research made possible through the development of molecular and molecular cytogenetic techniques. These technological advances have now allowed for a systematic search for genetic and environmental components to human nondisjunction. PMID- 7789362 TI - Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human. AB - Spontaneous mutation rates per generation are similar among the three species considered here--Drosophila, mouse, and human--and are not related to time, as is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they are among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation are: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9 month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-day generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the soma from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions. PMID- 7789363 TI - Population genetics of induced mutations. AB - The contribution of induced mutations to the burden of genetic disease in the context of population genetics is considered. A clear distinction is made between the effects of genetic disease and mutational events. Much of the existing burden of genetic disease is a consequence of mutations that occurred in the past. The problem of distinguishing between spontaneous and induced mutations is discussed. Molecular genetics techniques are blurring the definitions of these terms. Classical population genetics shows that the frequency of affected individuals will reach an equilibrium depending on the mutation rate and the selective pressure against affected individuals. Increasing the mutation rate or reducing the selective pressures would result in a new equilibrium with an increase in the frequency in subsequent generations of affected individuals with dominant and X linked mutant alleles. The increase in the number of recessive mutant alleles would be much slower and take many generations to reach the new equilibrium level. One assumption behind such equilibria is random mating. Changes in human demography with a rapid increase in population size, the breakup of small, relatively inbred subpopulations, and relaxed selective pressures will lead to a new equilibrium for recessive genes at probably higher frequencies. These factors will be the major contributors to increasing the burden of recessive genetic disease by increasing the total numbers of cases. The proportion of the population with a genetic disease will also continue to grow as a greater proportion of the population survives to late middle age and succumbs to diseases associated with old age, such as cancer, circulatory disease, dementias, and diabetes, each of which is likely to have a genetic component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789364 TI - The new human genetics. AB - This overview for the special issue of Environmental and Molecular Mutagenesis devoted to recent advances in human genetics relevant to mutagenesis briefly surveys the advances in the field. We present the evidence that trinucleotide repeat expansion can cause anticipation in human inherited disease. The finding that transposons are active in humans, as they are in other organisms, is reviewed. We present an example of two different diseases being caused by mutations in one gene. The role of mitochondrial mutations and parent-specific gene origin effects ("imprinting") are briefly reviewed; fuller reviews are provided in other articles in this special issue. Finally, the relevance of epigenetic inheritance by protein-protein interaction is included. PMID- 7789365 TI - Lessons learned from epidemiologic studies of environmental exposure and genetic disease. AB - The induction of germ cell mutations with ionizing radiation and chemicals has been clearly demonstrated in experimental animal test systems. Less is known about the effects of environmental and other exposures on human germ cells. Epidemiologic studies of atomic bomb and childhood cancer survivors and their offspring have generally not indicated an excess risk for a variety of adverse reproductive outcomes and childhood diseases, including those due to germ cell mutations. Other epidemiologic studies, including the investigation of cancer among the offspring of fathers employed at the Sellafield nuclear facility in Great Britain and studies of paternal occupation and birth defects, have found associations. This paper reviews these studies and the methodologic problems inherent in the epidemiologic approach to evaluating environmentally induced germ cell mutagenesis in humans. Epidemiologic studies incorporating newly developed techniques for the detection of mutations and abnormalities in sperm may provide the sensitivity needed to determine precisely the magnitude of risk. PMID- 7789366 TI - Mutagenesis and human genetic disease: dominant mutation frequencies and a characterization of mutational events in mice and humans. AB - Dominant deleterious traits are generally regarded to be the most relevant genetic endpoints when the expected increased mutational load of genetic diseases associated with exposure to mutagenic agents is considered in humans. At present, human risk estimation procedures rely on results from laboratory mammal germ-cell mutagenicity experiments as well as on data from human epidemiology and medical genetics. A comparison of the mouse and human data indicates that a small subset of loci, which when mutated result in a dominant phenotype, is contributing disproportionately to the observed mutation frequency. This is likely due to the fact that those loci with an observed high mutation frequency are inherently unstable, the function of such loci is critical, and/or the wild-type phenotype requires two copies of the normal gene (haploinsufficiency). The locus specificity of the observed spontaneous and induced mutation frequencies implies that efforts must be made to closely match those genetic endpoints screened in the mouse with the human genetic endpoints considered relevant in estimating the genetic risk after exposure to mutagenic agents. The contributions to our understanding of the organization, function, and stability of the mouse and human genomes provided by molecular biological techniques should make compliance with this restriction feasible. PMID- 7789367 TI - Perspectives on molecular assays for measuring mutation in humans and rodents. AB - The original idea for this article was to examine the new molecular techniques for detection of mutation directly at the DNA level in exposed individuals or their offspring and to assess their relative advantages and disadvantages for mutation monitoring in humans and rodents. However, an examination of the articles and a comparison of the technology indicated that our constant quests for methods improvement were leading to some loss of insight into the important health-related questions that should be guiding these endeavors. As a result, individual methods are not covered here in great technical detail. Instead, a few molecular methods are presented in a general overview, along with some of the biological issues related to the detection of induced mutations within individuals and populations. Some hypothetical scenarios are also presented because molecular approaches will continue to change rapidly, and we must continually adjust our thinking to combine the useful attributes of each current and future technical approach with the most appropriate biological questions. PMID- 7789368 TI - The Marlboro man is still marching. PMID- 7789370 TI - Chaos in the prediction of sudden death. PMID- 7789369 TI - Ambulatory ischaemia. PMID- 7789371 TI - Atrial fibrillation and anticoagulant therapy. PMID- 7789372 TI - Acute myocardial infarction in the young--the role of smoking. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. AB - Patients who received thrombolytic therapy for acute myocardial infarction in a large international trial were divided into two groups on the basis of age; those < or = 40 years (n = 269) and those > 40 years (n = 7787). The younger group included more men (89.9% vs 75.9%, P = 0.009) and fewer patients had a history of coronary artery disease, hypertension, and diabetes mellitus. A family history of cardiovascular disease was significantly more prevalent among the young patients (53.4% vs 41.9%, P = 0.0002). Significantly more younger patients than older patients were smokers at the time of infarction (76.2% vs 42.9%, P < 0.0001) and the average number of cigarettes smoked per day was also significantly higher in young patients (27.8 +/- 14.3 vs 19.9 +/- 12.9, P < 0.01). Younger patients had a better outcome, with lower rates of cardiogenic shock (1.1% vs 7.0%, P = 0.0002), stroke (0.0% vs 1.9%, P = 0.02) and haemorrhage (1.9% vs 5.9%, P = 0.006), as well as a better Killip class at discharge (Killip > 1 in 4.5% vs 8.0%, P < 0.001), and lower hospital and 6-month mortality (0.7% and 3.1% vs 8.3% and 12%, P < 0.001, respectively). The better outcome of younger patients with acute myocardial infarction is related to their better baseline characteristics. Young patients with acute myocardial infarction have a strong family history of cardiovascular disease and a high prevalence of smoking. Smoking is the most important modifiable risk factor in these patients. PMID- 7789373 TI - Detection of ambulatory ischaemia is not of practical clinical value in the routine management of patients with stable angina. A long-term follow-up study. AB - It has been reported that medically treated patients with stable angina and positive exercise test for ischaemia have an adverse 1-2 year outlook if they are shown also to have transient, and predominantly silent, ischaemic episodes detected by ambulatory ST segment monitoring during their daily activities: it has been suggested that this investigation could be used to identify patients more likely to benefit from early investigation and treatment. We assessed the long-term (up to 65 months) prognostic significance of transient ischaemic episodes during daily activities in 172 patients routinely attending cardiac outpatients with medically treated stable angina who had undergone exercise testing and 48 h of ambulatory ST segment monitoring between February 1988 and August 1989 for this purpose. A positive exercise test for ischaemia was not a prerequisite for inclusion. One hundred and four patients (60.5%) had a positive exercise test for ischaemia and 72 (42%) had transient ischaemia during daily activities (63 had both tests positive). Over a median 50-month follow-up period 54 patients suffered at least one cardiac event (primary event: cardiac death n = 7; non-fatal myocardial infarction n = 11; unstable angina n = 18; elective CABG/PTCA n = 18). Two further patients suffered non-cardiac death. Cardiac events, either objective (cardiac death or non-fatal myocardial infarction) or subjective (unstable angina or revascularisation) were no more likely to occur in those with transient ischaemia during daily life when compared with those without, at follow-up times up to 65 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789374 TI - Pre-hospital triage of patients with suspected myocardial infarction. Evaluation of previously developed algorithms and new proposals. AB - OBJECTIVE: To evaluate previously developed algorithms for the improvement of pre hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS: Patients with symptoms of possible cardiac origin, who were seen by a general practitioner and subsequently referred to hospital in the municipality of Rotterdam. METHODS: Prior to hospital admission, patients with suspected acute coronary disease recorded their symptoms by standardized questionnaire and a computerized ECG was made. All patients were hospitalized and a final diagnosis was established. Algorithms proposed by other investigators to distinguish patients with, from those without, acute cardiac disease were tested. MAIN OUTCOME: Identification of patients whose likelihood for acute cardiac pathology was low (stable angina, atypical chest pain, other pathology) or high (myocardial infarction, unstable angina). RESULTS: A total of 1005 patients were studied. Forty-two percent had myocardial infarction or unstable angina pectoris. Evaluation of previously developed algorithms showed that their diagnostic accuracy was poor in the pre-hospital setting. In a separate multivariate analysis, six characteristics from the clinical history and an electrocardiogram appeared to be independently and significantly associated with acute cardiac pathology. The presence of an abnormal ECG proved to be the most important predictor. CONCLUSIONS: The hospital-based algorithms were unsuitable as a predictor for pre-hospital acute cardiac pathology. A new practical hospital admission model was developed, based on six clinical predictors, including analysis of an electrocardiogram. Following appropriate validation, this out-of hospital protocol may lead to better triage decisions by the general practitioner. PMID- 7789375 TI - Outcome after thrombolytic therapy of nine cases of myopericarditis misdiagnosed as myocardial infarction. AB - Anecdotal reports have suggested that cardiovascular complications may occur if thrombolytic therapy is performed in cases of pericarditis misdiagnosed as acute myocardial infarction. From 1980 to 1993, 47 cases of myopericarditis mimicking myocardial infarction have been admitted to our institution. The misdiagnosis was made because of clinical onset characterized by a typical chest pain, and/or localized ST segment elevation. Since 1987, nine (9/9 males, age 40 +/- 14 years) out of the 47 patients (19%) have been treated with a thrombolytic agent (streptokinase 4/9, rt-PA 5/9) followed by intravenous heparin. This treatment was started during the pre-hospital phase (2/9) and while in hospital (7/9). No pericardial rub was present; ST segment elevation was mainly localized in inferior and lateral leads; no Q wave developed; median creatine kinase rise was 268 units (range 38 to 1280), and only one patient had a small pericardial effusion. The mean level of fibrinogen after thrombolysis was 1.72 g.l-1 (range 0.10 to 4.50). In all cases, typical ECG changes were present suggesting pericarditis with a subsequent return to a normal ECG. No severe cardiac or pericardial complication or arrhythmia occurred; only one patient developed a non compressive and resolvable pericardial effusion. Cardiac catheterizations (coronary and left ventricular angiographies) were normal when performed (5/9). Long-term follow-up (mean 46 +/- 29 months) was favourable without any coronary events. In conclusion, thrombolytic therapy was uncomplicated in our patients with myopericarditis simulating evolving myocardial infarction. PMID- 7789376 TI - Continuous monitoring of energy metabolites using microdialysis during myocardial ischaemia in the pig. AB - A diagonal branch of the left anterior descending artery was occluded for 80 min. One microdialysis probe was inserted in the ischaemic area and two in the non ischaemic areas. In six animals radiolabelled microspheres were injected before and during ischaemia and after reperfusion to monitor flow. Arterial and pulmonary artery pressures, pulmonary capillary wedge pressure and cardiac output were followed-up. Radiolabelled microsphere distribution confirmed the reduction of myocardial blood flow during coronary artery occlusion, with flow returning to normal values upon reperfusion. Rate pressure product as an index of heart work was stable throughout the 80 min ischaemic period, but increased at reperfusion. Dialysates from non-ischaemic tissue showed stable baseline values. In ischaemic tissue, lactate increased by 300% and pyruvate levels decreased by 50% within 15 min. Adenosine increased rapidly five-fold, but started to decline after 15 min of ischaemia. Inosine showed a slower but a marked 20-fold increase, decreasing at the end of the ischaemic period. Hypoxanthine increased five-fold during the first 30 min. Finally, guanosine showed a slow increase to about four times above basic values. Microdialysis was an excellent tool for the continuous monitoring of myocardial metabolites during ischaemia. Adenosine appeared to be a more sensitive marker of early ischaemia than lactate, although interestingly, adenosine levels had decreased already after 15 min, most probably due to intracellular accumulation of protons and Pi. PMID- 7789377 TI - Medical treatment of myocardial infarction in France and Northern Ireland. Results from the ECTIM study. Enquete cas-Temoins de l'Infarctus du Myocarde. AB - As part of the ECTIM Study, the medical treatment given to male patients (25-64 years) 3 to 9 months after myocardial infarction (MI) were analysed in France and Northern Ireland. On univariate analysis, hypolipidaemic drugs, angiotensin converting enzyme inhibitors and antiarrhythmic drugs were found to be prescribed more frequently in France, while beta-blockers were more common in Northern Ireland. No differences were found for diuretics, calcium channel blockers, antithrombotic and anti-anginal drugs, although the Northern Irish patients were mainly on antiplatelet drugs and nitrates, while the French patients received nitrates and non-nitrates, as well as oral anticoagulants and antiplatelet drugs in similar amounts. These differences remained after adjustment for personal history of diabetes, hyperlipidaemia, hypertension, and previous myocardial infarction, but the beta-blocker prescription was no longer significant. When the French centres were analysed, patients from Strasbourg were more frequently on oral anticoagulants and diuretics and less frequently on antiplatelet drugs, while patients from Toulouse had fewer anti-anginal drugs. Hence, although the current guidelines for secondary prevention of myocardial infarction are generally well applied in France and Northern Ireland, significant differences exist regarding the choice of the active drug. PMID- 7789378 TI - Exercise producing alterations in the signal-averaged electrocardiogram in patients after myocardial infarction. AB - Late potentials are considered to be a marker for regional slow conduction which might predispose to reentrant ventricular arrhythmias. Since these arrhythmias may be induced by ischaemia it may be speculated that exercise-induced myocardial ischaemia may trigger late potentials. Exercise testing was performed in 53 patients early after myocardial infarction and in 20 healthy controls. Typical 12 lead ECG and signal averaged ECG (SA-ECG) from 12 leads were recorded before and after exercise testing. Changes in filtered QRS (QRS) and low amplitude signal durations, and in the root mean square voltage of the last 40 ms of the QRS complex (RMS40) were analysed. Thirty patients developed ST changes, consistent with transient ischaemia, that persisted during the SA-ECG recording after exercise. There were significant differences between baseline SA-ECG and SA-ECG after exercise in patients with positive exercise tests (QRS, 102 +/- 15 ms vs 114 +/- 15 ms (P < 0.01). LAS, 36 +/- 12 ms vs 42 +/- 11 ms (P < 0.05), and RMS40, 29 +/- 14 microV vs 20 +/- 13 microV (P < 0.01). No differences were observed in SA-ECG parameters in either patients with negative exercise tests or in controls. During follow-up, four patients died suddenly; all four had positive exercise tests and in three of them late potentials were induced by exercise. We conclude, that in post-infarction patients with positive exercise tests SA-ECG parameters deteriorate after exercise. This suggests that exercise-induced ischaemia triggers development of late potentials. PMID- 7789379 TI - Heart rate variability and functional severity of congestive heart failure secondary to coronary artery disease. AB - To investigate the behaviour of heart rate variability (HRV) with the advancing severity of heart failure (CHF) we studied 20 normal subjects and 80 coronary artery disease (CAD) patients in sinus rhythm. CAD patients were selected consecutively in order to form four equal groups of 20 subjects with different degrees of CHF according to the New York Heart Association (NYHA) functional classification. In each subject a 24 h ECG Holter tape was recorded and subsequently analysed to obtain measures of heart rate and HRV. We used several measures of HR and both spectral and non-spectral measures of HRV. Among these we employed the width of the R-R interval distribution over 24 h at three different heights (TV, 10%Var, 50%Var). The CAD group showed significantly lower HRV counts and smaller spectral components than controls. However, these differences were due to the presence of CHF rather than to CAD. Indeed, a progressive and significant increase in heart rate and a contemporary decrease in HRV was observed with the advancing severity of CHF. Class IV patients had the smallest HR variation; the spectral composition in this group was barely detectable. The decrease in time domain measures of HRV followed the increase in NYHA Class in a progressive and regular pattern, while the low frequency and high frequency spectral power showed the largest reduction from NYHA Class I to NYHA Class II patients. No significant change was demonstrated in NYHA Class I patients as compared to Controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789381 TI - Clinical implications of pleomorphic ventricular tachycardias on oral sotalol therapy. AB - In 90 consecutive patients with coronary artery disease and sustained monomorphic ventricular tachycardia, who were treated with oral sotalol and underwent programmed stimulation to determine drug effectiveness, the influence of sotalol on induced ventricular tachycardia morphology was retrospectively examined. In 54 patients (60%) sotalol rendered the tachycardia non-inducible. However, contrary to drug-testing with class I antiarrhythmic agents, induction of multiple morphologies at baseline study did not predict failure of subsequent drug-testing with sotalol. In the remaining 36 patients (40%), in whom sotalol did not modify inducibility, 21 patients (i.e. a total of 23%) manifested at least one new morphology during electropharmacological testing on sotalol. This effect was independent of the degree of left ventricular dysfunction, infarct location and numbers of morphologies at baseline, but corresponded with drug-induced changes in refractoriness. This observation may be related to a proarrhythmic effect of sotalol. Slowing of ventricular tachycardia rate and changes in morphology may have implications in patients receiving implantable cardioverter-defibrillators or those undergoing ablative procedures. PMID- 7789380 TI - Sudden cardiac death in hypertrophic cardiomyopathy. Variability in phenotypic expression of beta-myosin heavy chain mutations. AB - BACKGROUND: Recent identification of mutations in the beta-myosin heavy chain gene (MYH7), a major responsible gene for HCM, has provided the opportunity to characterize genotype-phenotype correlation in HCM families. In this study we analysed the phenotypic expression of two beta-myosin heavy chain (beta MHC) mutations in three unrelated HCM families. METHODS: Living individuals from three unrelated HCM families (Families 1, 2, and 3) were screened by history, physical examination, electrocardiography, and two-dimensional echocardiography. Blood was collected from all individuals for DNA extraction. Polymerase chain reaction (PCR), restriction endonuclease digestion and chemical cleavage were utilized for detection of mutations. All mutations were confirmed by sequence analysis. RESULTS: Identification of mutations: A missense mutation in exon 13 of the beta MHC gene (Arg403 Gln) was detected in HCM patients from Families 1 and 2. PCR amplification of the exon 13 DNA, followed by Ddel digestion of the PCR product and gel electrophoresis, showed two fragments of 84 and 70 bp in normal individuals and four fragments of 84, 70, 52 and 32 bp in HCM patients. Sequence analysis showed substitution of an adenine for guanine at coding position 1208. In Family 3, a missense mutation in exon 16 of the beta MHC gene (Val606 Met) was detected in HCM patients. Chemical cleavage of the PCR products showed an uncleaved product of 337 bp in the normal individuals, while in the affected individuals, in addition to the uncleaved product, a 90 bp cleaved product was also detected, indicating the presence of a mismatch in one allele. Sequence analysis showed substitution of an adenine for guanine in coding position 1817. CLINICAL CHARACTERISTICS: Seven members of Family 1 had HCM, of whom five are alive. One patient died from sudden cardiac death (SCD) and another from recurrent cerebral emboli. In Family 2, 15 individuals had HCM of whom nine have died, seven from SCD. The mean age at the time of SCD was 33 years. The third family is comprised of 11 affected individuals and one obligate carrier, of whom one patient died at age 17 from progressive heart failure. Two additional individuals in this family have also succumbed to SCD to age 60. A variety of clinical and echocardiographic manifestations of HCM were present in each family. Logrank test of Kaplan-Meier survival curves indicates that Arg403 Gln mutation was associated with a poor prognosis in HCM families as compared to Val606 Met (P = 0.034). CONCLUSIONS: beta MHC mutations despite showing variable clinical and echocardiographic manifestations of HCM are predictors of survival in HCM families. PMID- 7789382 TI - Velocity distributions in the left ventricular outflow tract in patients with valvular aortic stenosis. Effect on the measurement of aortic valve area by using the continuity equation. AB - The cross-sectional velocity distribution in the left ventricular outflow tract was studied in 40 patients with valvular aortic stenosis. Doppler colour flow mapping and a time-interpolation method were used to construct the cross sectional velocity and time-velocity integral (TVI) profiles at different levels. By using pulsed Doppler, the subaortic flow velocity was sampled from the anterior, middle and posterior regions along the diameter of the left ventricular outflow tract (at 0.5 to 1.0 cm proximal to the aortic anulus) in the apical long axis view. Thus, for each patient, three aortic valve areas were calculated by using the continuity equation. Each patient was assigned to one of three subgroups according to the left ventricular ejection fraction (EF): subgroup I with EF < or = 25% (n = 10), subgroup II with 25% < EF < or = 50% (n = 17) and subgroup III with EF > 50% (n = 13). Velocity distributions in the three subgroups were compared to each other. RESULTS: (1) The velocity distribution in the left ventricular outflow tract was skewed with the highest velocities and TVIs along the anterior wall and septum. The skewness of the velocity distribution was more pronounced in the apical long axis view than in the four chamber view (P < 0.05). The extent of skewness of the TVI profile was positively correlated to the left ventricular EF both in the long axis view (r = 0.63; P < 0.001) and in the four chamber view (r = 0.57; P < 0.001). (2) Pulsed Doppler sampling from different regions along the diameter produced different TVIs, and therefore yielded significantly different calculated aortic valve areas, especially in subgroup III. Due to the skewness of the velocity distribution in the left ventricular outflow tract, location of the pulsed Doppler sample volume significantly affects the accuracy of aortic valve area calculation by using the continuity equation, especially in patients with relatively high left ventricular EF. In patients with low EF, selection of pulsed Doppler sampling site is less important. PMID- 7789383 TI - Characteristics of infective endocarditis in France in 1991. A 1-year survey. AB - OBJECTIVE: To update data on incidence and characteristics of infective endocarditis in France. BACKGROUND: Numerous studies have shown that the incidence and course of infective endocarditis remain stable in spite of advances in treatment and of prophylactic recommendations. METHODS: A survey of all consecutive cases of infective endocarditis was conducted over 12 months in all the institutions of three French regions. RESULTS: Data were collected from 415 cases of definite (32%), probable (53%), and possible (15%) infective endocarditis. The adjusted annual incidence was 24.3 cases per million inhabitants. Thirty-four percent of the patients had no previously known heart disease, 33% had native valve disease, 22% had a prosthetic valve, and 11% had miscellaneous underlying conditions. Infective endocarditis was located solely on the mitral valve in 39%, solely on the aortic valve in 36%, and on the tricuspid valve in 6%. Echocardiography showed a vegetation on the mitral valve in 39%, on the aortic valve in 29%, and on the tricuspid valve in 8%. The causal microorganism was identified in 92%; it was a Streptococcus in 58%, and a Staphylococcus in 23%. Twenty patients were intravenous drug users, and 45 had had a medical or a surgical procedure, which might be associated with the occurrence of infective endocarditis. During the first 2 months after admission, 24% of the patients underwent surgery, and 17% of all patients died. CONCLUSIONS: Despite medical and surgical advances, infective endocarditis remains frequent and severe in France. PMID- 7789384 TI - Transoesophageal echocardiographic follow-up of patients with surgically treated aortic aneurysms. AB - In the present study, biplane transoesophageal echocardiography (TEE) was scheduled as part of an aneurysm surveillance programme during routine ambulatory follow-up of 37 patients following aortic aneurysm surgery. Time from surgery ranged from 3-72 months. Twenty-two patients had had aortic dissection and 15 non dissecting aneurysms. Nineteen patients received an interposition graft of the ascending aorta, 12 valved conduit and six an interposition graft of the descending thoracic aorta. TEE showed enlargement of the sinus of Valsalva > 45 mm in seven patients. Dilatation > 45 mm of one or more aortic segments was found in four patients. An intimal flap was present in all patients, with primary aortic dissection if the initial dissection extended beyond the replaced segment. This was the case in 17 of 22 patients with aortic dissection. One to four intimal tears were identified in 15 of these patients. In all patients with intimal tears, flow was detected by colour flow Doppler in the false lumen. Thrombus formation was nil or minimal in the false lumen in 12 patients. TEE significantly influenced further management in 14 of 37 patients (38%). More frequent follow-up was scheduled in eight patients. Aortic surgery was performed electively for the second or third time in six patients based on TEE findings. We conclude that after surgical repair of aortic aneurysm, the incidence of pathological findings by TEE is high. These may have significant influence on further patient management and emphasize the need for careful follow-up. PMID- 7789385 TI - Assessment of aortic regurgitation severity by magnetic resonance imaging of the thoracic aorta. AB - A new method of assessing the severity of aortic regurgitation severity by magnetic resonance imaging has been developed. Two groups were studied: 20 controls (age = 58 +/- 19 years) without valvular aortic disease, and 24 patients (age = 62 +/- 13 years) with chronic aortic insufficiency evaluated by magnetic resonance and aortic root cineangiography within 1 week of each other. A magnetic resonance sequence (TR = 35 ms/TE = 12 ms/flip angle = 20 degrees/magnet = 1.5 T) was acquired in a plane containing the thoracic aorta. A transverse saturation band 30 mm wide was positioned 30-40 mm above the aortic valve. Aortic insufficiency was graded; the importance of end-diastolic retrograde movement in the saturation band in the descending aorta was noted. Magnetic resonance was also compared to Doppler echocardiography in 20 patients. In the controls, we found that retrograde blood flow was absent (18/20) or mild (2/20). In contrast, the presence of marked retrograde movement in a saturation band across the thoracic aorta was always associated with severe aortic regurgitation (angiographic grade III or IV). This rapid method (imaging time less than 20 min) can be applied in most patients with aortic regurgitation and is likely to be helpful when echocardiography is not possible or gives inconclusive results. PMID- 7789386 TI - Clinical value of immediate thallium-201 reinjection imaging for the detection of ischaemic heart disease. AB - Immediate reinjection of thallium-201 after acquisition of the stress images followed by imaging 60 min later has been proposed as a novel time-saving and patient-convenient approach for the evaluation of myocardial ischaemia and viability. The objective of this study was to establish the clinical value of thallium-201 stress immediate reinjection imaging in the evaluation of patients with suspected and known coronary artery disease. Quantitative planar thallium 201 stress immediate reinjection imaging was performed in 138 patients with undiagnosed chest pain, of whom 114 underwent cardiac catheterization and 24 had a < 5% likelihood for coronary artery disease; 56 patients had previously suffered a myocardial infarction. Sensitivities and accuracies were determined for coronary artery disease, reversible myocardial ischaemia, and myocardial viability. Of the 138 patients studied for coronary artery disease, thallium stress scintigraphy identified 85 of 93 patients with angiographically proven coronary artery lesions (overall sensitivity 91%). The normalcy rate in the low likelihood patients was 88% (21 of 24 patients) and the overall diagnostic accuracy was 83%. In the 56 patients who had suffered a previous myocardial infarction, and in whom the suitability for reversible ischaemia was sought, the overall patient-related sensitivity and accuracy were 93% and 92% respectively. In the 56 patients with a previous myocardial infarction a total of 168 vessel regions were studied to detect viability. Of the 142 normal or hypokinetic regions, 127 regions were scintigraphically identified as viable (sensitivity 89%). The thallium stress immediate reinjection imaging protocol is an appropriate clinical approach in patients with undiagnosed chest pain. The combined identification of stress-induced ischaemia and viability by thallium stress immediate reinjection imaging provides adequate algorithms allowing optimal management and risk assessment in the individual cardiac patient. PMID- 7789387 TI - Cyanosis and clubbing in a patient with iatrogenic Lutembacher syndrome. AB - A patient with rheumatic mitral and aortic stenosis is described in whom balloon dilatation of the mitral valve was complicated by an iatrogenic atrial septal defect with a small left to right shunt. Over the course of 4 years, the patient became progressively cyanosed and clubbed and was found to have reversed the shunt across the atrial septal defect due to the occurrence of severe tricuspid stenosis. The tricuspid valve was successfully dilated with re-establishment of a net left to right shunt. This syndrome, the first of its kind, should be appropriately termed the reversed Lutembacher syndrome. PMID- 7789389 TI - Tuberculous cardiac tamponade and AIDS. AB - Tuberculosis, usually extrapulmonary, is often associated with AIDS but tuberculous pericarditis is a rare manifestation in this group. We report three patients with tuberculous pericarditis as the first manifestation of AIDS. PMID- 7789388 TI - Multiplane transoesophageal echocardiography detection of a papillary fibroelastoma of the aortic valve causing myocardial infarction. AB - Primary aortic valve tumours are rare. A patient is reported with a papillary fibroelastoma attached to the edge of the right coronary aortic cusp. This tumour was diagnosed by multiplane transoesophageal echocardiography after the patient experienced an acute inferolateral myocardial infarction. Multiplane transoesophageal echocardiography was useful to visualize and identify the precise point of attachment of the tumour, enabling cardiac surgeons to plan aortic valve repair rather than replacement. PMID- 7789390 TI - Nuclear medicine in cardiology: a position paper for an open debate. EANM Executive Committee. PMID- 7789391 TI - Quantitative assessment of technetium-99m methoxyisobutylisonitrile planar perfusion heart studies: application of multivariate analysis to patient classification. AB - A quantified evaluation of planar cardiac perfusion scintigrams (the objective of the study), obtained using technetium-99m methoxyisobutylisonitrile (MIBI) was performed on the basis of an analysis of circumferential profile curves, representing the perfusion as seen in three typical projections. The analysis involved the curves obtained both at rest and after stress, and was based on a comparison of their shape (trend) with the normal trend (normative evaluation). The latter was obtained by means of an original method of iterative fitting of individual curves into the database. The base consisted of curves recorded in 53 patients (separately in males and females) with normal perfusion of the left ventricle (group I, the reference group). A group of 90 patients suspected of having coronary artery disease (group II) was subdivided into two subgroups on the basis of coronary arteriography: (a) those with and (b) those without critical stenosis of at least one artery. Profile curves characterising the LV perfusion were obtained at rest and after stress. Defects of perfusion were quantified by comparison of individual curves with the normal trends. By means of multivariate analysis it was demonstrated that vectors of mean values characterising the scintigraphically assessed defects of LV perfusion in the two subgroups of group II differed very significantly (P < 10(-5)). Applying methods of discriminant analysis, a classification of patients from group II was performed into those with probable defects of perfusion and those free of such defects. The sensitivity, specificity and accuracy of diagnosis of coronary ischaemia, based on quantified planar 99mTc-MIBI scintigraphy, reached 86%, 87% and 87%, respectively. PMID- 7789392 TI - Indium-111 octreotide scintigraphy in neurofibromatosis. AB - Scintigraphy with the radiolabelled somatostatin analogue indium-111-DTPA-D-Phe-1 octreotide has recently been proposed for the imaging of CNS neoplasms expressing somatostatin receptors. While meningiomas are imaged with high sensitivity, neurinomas do not take up octreotide owing to the lack of somatostatin receptors. Neurofibromatosis is a relatively uncommon disorder in which meningiomas and neurinomas often occur in the same patient. Differential diagnosis between these two tumours by computed tomography and magnetic resonance imaging can be difficult. This study reports on 111In-octreotide scintigraphy in four patients with neurofibromatosis. 111In-octreotide scintigraphy was shown to be very helpful in the in vivo differential diagnosis: all four meningiomas showed intense tracer uptake, while all 15 neurinomas were negative (P < 0.001 by Fisher's exact test). It may be concluded that scintigraphy with 111In-octreotide is a useful diagnostic procedure in neurofibromatosis, complementing standard neuroradiological imaging procedures. PMID- 7789393 TI - Dissociation of indium from indium-111-labelled diethylene triamine penta-acetic acid conjugated non-specific polyclonal human immunoglobulin G in inflammatory foci. AB - Several investigators have reported retention of indium-111 in infectious foci after intravenous injection of 111In-labelled immunoglobulin G (IgG). With this study we intended to test the hypothesis that, upon administration of 111In diethylene triamine penta-acetic acid (DTPA-IgG), 111In is retained in the infectious foci after dissociation from IgG. Therefore we measured the tissue distribution of double-labelled 111In-DTPA-IgG-(carbon-14) in rats with a focal infection and compared the results with corresponding data for DTPA-IgG-(14C). DTPA-conjugated IgG was labelled with 111In via citrate transchelation. 111In DTPA-IgG and DTPA-IgG were labelled with 14C through methylation. High performance liquid chromatography (HPLC) and instant thin-layer chromatography analysis were performed to test the in vitro stability of the labelled proteins. Young Wistar rats with a Staphylococcus aureus infection of the left calf muscle were injected intravenously with 0.2 ml of a solution containing either 0.4 MBq 111In and 30 kBq 14C or 30 kBq 14C labelled to 80 micrograms IgG. Groups of five rats were sacrificed at 2, 6, 24, and 48 h. p.i. Activity uptake was determined for plasma, urine, abscess, muscle and various other tissues. Averages and standard deviations were calculated for groups of five rats. HPLC analysis was performed on plasma and urine samples taken up to 48 h p.i. The radiochemical purity of the IgG preparations was > 95%. The labelled preparations appeared stable in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789394 TI - Regional ventilatory evaluation using dynamic SPET imaging of xenon-133 washout in obstructive lung disease: an initial study. AB - Regional ventilatory abnormalities in obstructive lung disease were evaluated by dynamic single-photon emission tomography (SPET) of pulmonary washout of xenon 133 (133Xe) gas. The subjects included seven healthy volunteers. 17 patients with obstructive lung disease, and seven patients with restrictive lung disease. Following 6 min of inhalation of 133Xe gas (60-72 MBq/l), equilibrium and subsequent washout SPET images during spontaneous breathing were sequentially acquired every 30 s for 6-7 min, using a triple-head SPET system with the return mode of continuous repetitive rotating acquisition. A gravity-induced gradient of ventilation was demonstrated in the volunteers' lungs. Compared with the normal subjects, all the patients with obstructive disease showed abnormal 133Xe retention on the washout SPET images, with or without abnormalities on chest X ray computed tomography, whereas the patients with restrictive disease did not show any significant delays in washout. This modality may assist in the evaluation of the three-dimensional dynamic process of ventilatory abnormalities in obstructive lung disease. PMID- 7789395 TI - Evaluation of results of the prostigmine-morphine test with quantitative hepatobiliary scintigraphy: a new method for the diagnosis of sphincter of Oddi dyskinesia. AB - Attempts have long been made to use the prostigmine-morphine provocation test for the selection of postcholecystectomy patients suffering from sphincter of Oddi (SO) dyskinesia. Since the whole procedure is based upon the evaluation of subjective complaints, this test has frequently been criticized. To improve the diagnostic value of this method, we have visualized SO spasms during prostigmine morphine provocation by means of quantitative hepatobiliary scintigraphy (QHBS). Twenty-two cholecystectomized patients with typical postprandial biliary pain were included in this study. In the first series of studies, QHBS with technetium 99m 2,6-diethylphenylcarbamoylmethyl-diacetic acid was performed in each patient 2 days before prostigmine-morphine provocation. The time to peak activity (Tmax) and the half-time of excretion (T1/2) over the liver parenchyma (LP), hepatic hilum (HH) and common bile duct (CBD), and the duodenum appearance time (DAT), were determined and served as control values. In the second series of experiments, sphincter spasms were evoked by prostigmine-morphine administration and visualized by means of QHBS. The same parameters were evaluated and serum levels of aspartate aminotransferase (AST) were determined simultaneously at regular intervals. In 12 patients who responded to prostigmine-morphine provocation with typical biliary pain and a significant AST elevation (Nardi positive group) the hepatobiliary scintigram demonstrated a marked biliary obstruction. Tmax and T1/2 over the LP, HH and CBD were significantly increased, while DAT was significantly longer relative to the corresponding data obtained without provocation. Four of the remaining ten patients indicated atypical abdominal pain during prostigmine-morphine provocation, but the AST level remained unchanged in all ten (Nardi negative group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789397 TI - Reverse redistribution on planar thallium scintigraphy: relationship to resting thallium uptake and long-term outcome. AB - Reverse redistribution (RR) of thallium-201 has been associated with both acute and healed myocardial infarction, and with recent thrombolysis. The physiologic basis for RR in coronary artery disease (CAD) is unclear but may be related to an admixture of viable and scarred myocardium within the RR segment. We performed thallium reinjection imaging at rest to better characterize RR defects in patients with chronic CAD. We found enhanced uptake of 201Tl in 52% of RR segments after reinjection, consistent with significant regional viability that was not evident on redistribution images. We then used a logistic multiple regression analysis to determine whether RR alone or in combination with other scintigraphic findings could predict patient outcome. The results showed that severe RR was an independent predictor of patient outcome. We conclude that RR may have prognostic significance in chronic CAD. PMID- 7789396 TI - Preparation and biodistribution of yttrium-90 Lipiodol in rats following hepatic arterial injection. AB - In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate 90Y from strontium-90. 90Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2 ethylhexyl) phosphate, while 90Sr was washed out. A hexadentate nitrogen-donor chelating ligand N,N,N',N'-tetrakis(2-benzymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained 90Y from the RP-18 column with EDTB Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi 90Y Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789398 TI - Spatial registration of echocardiographic and positron emission tomographic heart studies. AB - A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-18-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized. PMID- 7789401 TI - Per operative localization of a carcinoid tumour of the breast using indium-111 pentetreotide and a nuclear surgical probe. AB - A 69-year-old woman presented with a single enlarged lymph node in the left axilla. Clinical examination and other investigations, including various imaging methods, failed to reveal the primary tumour. However, indium-111 pentetreotide scan revealed a site of uptake in the anterior region of the left thorax. Peroperative imaging with 111In-pentetreotide confirmed the tumour uptake and use of a nuclear surgical probe allowed precise localization of the tumour, which was completely resected. PMID- 7789402 TI - 1994 recipient of the Paul Kayser International Award of Merit in Retina Research. PMID- 7789400 TI - Nitroimidazoles and imaging hypoxia. AB - Decreased tissue oxygen tension is a component of many diseases. Although hypoxia can be secondary to a low inspired pO2 or a variety of lung disorders, the commonest cause is ischemia due to an oxygen demand greater than the local oxygen supply. In tumors, low tissue pO2 is often observed, most often due to a blood supply inadequate to meet the tumor's demands. Hypoxic tumor tissue is associated with increased resistance to therapy. In the heart tissue hypoxia is often observed in persistent low-flow states, such as hibernating myocardium. In patients with stroke, hypoxia has been associated with the penumbral region, where an intervention could preserve function. Despite the potential importance of oxygen levels in tissue, difficulty in making this measurement in vivo has limited its role in clinical decision making. A class of compounds known to undergo different intracellular metabolism depending on the availability of oxygen in tissue, the nitroimidazoles, have been advocated for imaging hypoxic tissue. When a nitroimidazole enters a viable cell the molecule undergoes a single electron reduction, to form a potentially reactive species. In the presence of normal oxygen levels the molecule is immediately reoxidized. This futile shuttling takes place for some time, before the molecule diffuses out of the cell. In hypoxic tissue the low oxygen concentration is not able to effectively compete to reoxidize the molecule and further reduction appears to take place, culminating in the association of the reduced nitroimidazole with various intracellular components. The association is not irreversible, since these agents clear from hypoxic tissue over time. Initial development of nitroimidazoles for in vivo imaging used radiohalogenated derivatives of misonidazole, such as fluoromisonidazole, some of which have recently been employed in patients. Two major problems with fluoromisonidazole are its relatively low concentration within the lesion and the need to wait several hours to permit clearance of the agent from the normoxic background tissue (contrast between lesion and background typically < 2:1 at about 90 min after injection). Even with high-resolution positron emission tomographic imaging, this combination of circumstances makes successful evaluation of hypoxic lesions a challenge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789399 TI - Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems. AB - After a brief review of the history of the development of technetium-99m-labeled radiopharmaceuticals, the use of technetium chelates in high-capacity systems is discussed. The latter are used in the study of five organ systems, the kidneys, liver, bone, brain, and heart. The chemical characterization of 99mTc complexes is also reviewed, followed by discussion of the various approaches to the labeling of proteins with direct labeling, the preformed chelate approach, and the antibody chelator conjugate approach. Thereafter, the labeling of biochemicals with 99mTc for use with easily saturated sites, e.g., receptors and enzymes, is considered. Finally, attention is given to factors that affect the preparation of high specific activity, high affinity 99mTc-labeled biochemicals. PMID- 7789403 TI - Nuclear light scattering, disulfide formation and membrane damage in lenses of older guinea pigs treated with hyperbaric oxygen. AB - Nuclear cataract, a major cause of loss of lens transparency in the aging human, has long been thought to be associated with oxidative damage, particularly at the site of the nuclear plasma membrane. However, few animal models have been available to study the mechanism of the opacity. Hyperbaric oxygen (HBO) has been shown to produce increased nuclear light scattering (NLS) and nuclear cataract in lenses of mice and human patients. In the present study, older guinea pigs (Initially 17-18 months of age) were treated with 2.5 atmospheres of 100% O2 for 2-2.5-hr periods, three times per week, for up to 100 times. Examination by slit lamp biomicroscopy showed that exposure to HBO led to increased NLS in the lenses of the animals after as few as 19 treatments, compared to lenses of age-matched untreated and hyperbaric air-treated controls. The degree of NLS and enlargement of the lens nucleus continued to increase until 65 O2-treatments, and then remained constant until the end of the study. Exposure to O2 for 2.5 instead of 2 hr accelerated the increase in NLS; however, distinct nuclear cataract was not observed in the animals during the period of investigation. A number of morphological changes in the experimental lens nuclei, as analysed by transmission electron microscopy, were similar to those recently reported for human immature nuclear cataracts (Costello, Oliver and Cobo, 1992). O2-induced damage to membranes probably acted as scattering centers and caused the observed increased NLS. A general state of oxidative stress existed in the lens nucleus of the O2-treated animals, prior to the first appearance of increased NLS, as evidenced by increased levels of protein-thiol mixed disulfides and protein disulfide. The levels of mixed disulfides in the experimental nucleus were remarkably high, nearly equal to the normal level of nuclear GSH. The level of GSH in the normal guinea pig lens decreased with age in the nucleus but not in the cortex; at 30 months of age the nuclear level of GSH was only 4% of the cortical value. HBO-induced changes in the lens nucleus included loss of soluble protein, increase in urea-insoluble protein and slight decreases in levels of GSH and ascorbate; however, there was no accumulation of oxidized glutathione. Intermolecular protein disulfide in the experimental nucleus consisted mainly of gamma-crystallin, but crosslinked alpha-, beta- and zeta-crystallins were also present.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789404 TI - Ciliary ganglion choline acetyltransferase activity in avian macrophthalmos. AB - While present evidence fails to support an etiologic mechanism for myopia based on accommodation or choroidal blood flow, atropine exhibits anti-myopia activity in many species. Accordingly, we studied choline acetyl transferase (ChAT) activity in the ciliary ganglion, uvea and retina of chicks with experimental macrophthalmos to identify a potential pathway for the moderation of eye growth by cholinergic neurons. Following unilateral lid suture or goggle, chicks were reared for 1 week under one of four lighting conditions known to induce macrophthalmos or myopia. Ocular tissues and ciliary ganglia were assayed for ChAT activity by measuring the conversion of 14C-acetyl CoA to 14C-acetylcholine. For some chicks, the goggles were removed at 1 week, and ChAT activity was measured 2 or 7 days later. Depending on the rearing condition, ciliary ganglion ChAT activity was depressed from 16 to 28% ipsilateral to the lid suture; enzyme activity also was reduced in the choroid of visually deprived eyes under most conditions. In contrast, lid suture resulted in no consistent trend in ChAT activity in either the anterior uvea or retina. For chicks wearing a unilateral goggle and reared under a 12:12 hr light/dark cycle, ChAT activity was depressed in the ciliary ganglion, anterior uvea and choroid on the visually deprived side. Following goggle removal to allow recovery from myopia. ChAT activity in the ciliary ganglion and uvea was returned toward that of the control side. The ciliary ganglion may participate in a neural pathway influencing the development of form-deprivation myopia. PMID- 7789405 TI - Quantitative analysis of the lens cell microstructure in selenite cataract using a two-dimensional Fourier analysis. AB - Using two-dimensional (2-D) Fourier methods, we analysed the cellular microstructure of three rat lenses: normal transparent, selenite-induced cataractous and selenite-treated plus a phase separation inhibitor (PSI) to prevent cataract. 2-D Fourier analysis of electron micrographs of the lens cells quantified the dimensions of the spatial fluctuations in electron density of the lens cell microstructure. The 2-D Fourier spectra of the transparent normal and PSI-treated lens cells were remarkably similar while those of the opaque selenite treated lens cells were dramatically different. In the opaque cells the contributions of large Fourier components (larger than half the wavelength of light) in the 2-D Fourier spectra were much greater than in the transparent cells. The results of the 2-D Fourier analysis of electron micrographs are consistent with the theory of transparency of the eye. PMID- 7789406 TI - Hippocalcin in rat retina. Comparison with calbindin-D28k, calretinin and neurocalcin. AB - The post-natal developmental expression in rat retina of four calcium-binding proteins belonging to the calmodulin-troponin-C family was investigated by immunohistochemistry using anti-calbindin-D28k, anti-calretinin, anti-hippocalcin and anti-neurocalcin polyclonal antibodies on paraffin sections from Wistar rat retinae aged from post-natal days 1 (P1), 5 (P5), 10 (P10), 20 (P20) to adulthood (8 weeks). Immunoblot using anti-hippocalcin and homogenates proteins from retina, cerebellar cortex, hippocampus and cerebellum was also performed. Hippocalcin immunoreactivity in adult rat retina was demonstrated by both immunohistochemistry and Western blot. During post-natal development, calbindin D28k, calretinin and neurocalcin immunoreactivity were detected at P1 in ganglion cells, whereas hippocalcin immunoreactivity was seen later at P5 in this cell layer. In the amacrine cell layer, neurocalcin immunoreactivity was detected at P5 and hippocalcin at P10. Calbindin-D28k was labelling the immature horizontal cell, calretinin was detected in nearly all ganglion cells and in some amacrine cells since P1. These three calcium-binding proteins do not seem to play a role in synaptogenesis which takes place later. We confirmed that calbindin-D28k appeared to be a good marker for horizontal cells. The presence of hippocalcin, a myristoylated calcium-binding protein belonging to the recovering subfamily and previously localized in few brain areas has been detected for the first time in retina. PMID- 7789407 TI - The effect of arterial pressure on the ocular pressure-volume relationship in the rabbit. AB - The purpose of this study was to quantify the effect of mean arterial pressure (MAP) on the ocular pressure-volume relationship. The experiments were performed in pentobarbital anesthetized rabbits instrumented with occluders on the thoracic aorta and inferior vena cava to control MAP which was measured via a cannula in the central ear artery. To vary the ocular volume and measure the intraocular pressure (IOP), two 23 gauge needles were inserted through the pars plana into the vitreous: one needle was connected to a saline-filled syringe and the other needle was connected to a pressure transducer. In one group of animals (n = 5), pressure-volume curves were determined at MAPs of 100, 80, 60, 40 and 20 mmHg and post mortem by cumulative saline injections (2 microliters) every 1-1.5 sec. In a second group (n = 7), pressure-volume curves were obtained at MAPs of 80, 60 and 40 mmHg and post mortem by saline infusion at 0.5 microliter sec-1 until the IOP reached 100 mmHg. The infusion protocol was repeated in a third group (n = 11) where the choroidal flux and the concentration of moving blood cells (CMBC) were measured by a laser Doppler flowmeter as indices of choroidal blood flow and the blood volume, respectively. MAP had three primary effects on the ocular pressure volume relationship: (1) the baseline IOP varied exponentially with MAP, (2) the steepness of the initial portion of the pressure-volume curves was MAP-dependent and (3) the curves exhibited a 'plateau' as the IOP approached the prevailing MAP at MAPs > or = 40 mmHg. All of the curves in the living eye intersected and became indistinguishable from the post mortem curve when the IOP exceeded the prevailing MAP. The flux and CMBC measurements indicated that the MAP-dependence of the initial portion of the curves was due to failure of choroidal autoregulation and diminished increases in choroidal blood volume at the lower MAPs, and that the plateau portion of the curves was due to expulsion of blood from the eye. It is concluded that MAP has a significant effect on the ocular pressure-volume relationship. PMID- 7789408 TI - Metabolism of omega-3 fatty acids in patients with autosomal dominant retinitis pigmentosa. AB - Abnormalities in lipid metabolism have been reported in numerous patients with retinitis pigmentosa. As an initial step in evaluating these anomalies, two trials of fatty acid intervention were conducted with autosomal dominant retinitis pigmentosa (adRP) patients and controls. The first trial addressed absorption and incorporation of omega 3 long-chain fatty acids from a fish-oil concentrate into red blood cell (RBC) lipids. The utilization of omega 3 long chain fatty acids by adRP patients was found to be equivalent to that of controls. The second trial addressed the conversion of precursor, eicosapentaenoic acid (EPA, 20:5 omega 3), to end-product, docosahexaenoic acid (DHA, 22:6 omega 3), following oral supplementation of EPA ethyl ester. Although the levels of EPA and the intermediate, docosapentaenoic acid (22:5 omega 3), were both elevated by EPA supplementation in RBCs of adRP patients with rhodopsin gene mutations and controls, DHA production was elevated only in controls. Based on these results, we suggest the presence of a metabolic defect in the final stages of DHA biosynthesis. PMID- 7789409 TI - Effect of dietary fat and environmental lighting on the phospholipid molecular species of rat photoreceptor membranes. AB - We have previously shown that retinas of albino rats adapt to bright cyclic light (500-800 lx) by lowering the levels of docosahexaenoic acid (22:6n-3) in their rod outer segment (ROS) phospholipids. In the present study, we addressed the role of dietary fat in this process. Pregnant rats were kept in 1 lx or 250 lx cyclic illuminance (12L:12D) and fed diets containing 10% (by weight) of either hydrogenated coconut oil (COC, no n-3 or n-6 fatty acids), linseed oil (LIN, n-3 and n-6 fatty acids), or safflower oil (SAF, only n-6 fatty acids), starting 4 days before delivery. Pups were weaned at 3 weeks of age and continued on the same diet and light regime. At 12 weeks of age, 3 or 4 animals in each diet-light group were killed and the remaining animals were stressed continuously with 2000 lx light for 24 hr and then kept in 1 lx cyclic light for 10 days. Fatty acids and phospholipid molecular species (PLMS) of ROS membranes were determined. For prestressed groups, those animals fed the LIN diet had high levels of 22:6n-3 and PLMS containing 22:6n-3, with little 22:5n-6. Compared to the LIN group, the COC and SAF groups had lower levels of 22:6n-3- and 22:6n-3)-containing PLMS and higher levels of 22:5n-6 and molecular species containing 22:5n-6, such as 22:5n 6/22:6n-3, 16:0/22:5n-6 and 18:0/22:5n-6. Within each dietary group, animals raised in 250 lx cyclic illuminance had lower levels of 22:6n-3 and 22:5n-6 compared to those raised at 1 lx. This light effect was greater for 22:6n-3 in the LIN group than for 22:5n-6 in the SAF group. After the acute light stress, those animals raised in 1 lx showed dramatic reduction in PLMS containing 22:6n-3 and 22:5n-6, especially polyenoic species such as 22:6n-3/22:6n-3 in the LIN group and 22:5n-6/22:6n-3 in the COC and SAF groups. In contrast, animals raised in 250 lx showed much smaller changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789410 TI - Effect of dietary fat on the response of the rat retina to chronic and acute light stress. AB - We designed an experiment to study the role of light history and polyunsaturated fatty acids (PUFA) on the susceptibility of the albino rat retina to light damage. Albino rats were born to dams that had been kept in either 1 lx or 250 lx cyclic light for 0-4 days prior to delivery and fed one of three diets containing either 10% (by weight) hydrogenated coconut oil (COC, no n-3 nor n-6 fatty acids), safflower oil (SAF, high n-6, < 0.1% n-3 fatty acids), or linseed oil (LIN, high n-3, low n-6 fatty acids). After weaning, the rats were maintained in the same light environment and fed the same diets for 9 weeks, at which time some were killed and their retinas processed for morphometric analysis. Animals raised in bright cyclic light had shorter ROS lengths and thinner outer nuclear layers (ONL) than rats raised in dim cyclic light. The LIN animals had a thinner ONL than animals of the SAF or COC groups. Rats from each diet and light rearing groups were exposed to constant illumination of 2000 lx for 24 hr, after which they and non-exposed controls were placed in 1 lx cyclic light for 10 days and analysed for changes in ONL thickness. In the 250 lx (bright; B) groups, there was no effect of acute light stress on ONL thickness, although both control and stressed LIN animals had a thinner ONL than the corresponding COC and SAF groups. However, in the rats raised in 1 lx cyclic light, acute stress resulted in significant retinal damage (i.e. decrease in ONL thickness) in the three diet groups combined. The superior region was damaged the most and the severity was dependent on diet, as evidenced by the LIN group having a greater reduction in ONL thickness than the SAF group after light stress. From these results we conclude that rats on diets high in n-3 fatty acids are more susceptible to photoreceptor cell loss than animals fed n-6 or no polyunsaturated fatty acids when raised in dim cyclic light. These results show that both diet and light history play a role in the susceptibility of the retina to acute and chronic effects of light and suggest a role for lipid peroxidation in retinal light damage. PMID- 7789411 TI - Age-related changes in ganglioside composition in human lens. AB - We previously reported that human lens accumulates gangliosides in association with aging and senile cataract progression. Structural analysis revealed that gangliosides in human cataractous lenses were composed of ganglio-series gangliosides, such as GM3, GM2, GM1 and GD1a, and sialyl-Lewisx-containing neolacto-series gangliosides. Although Lewisx-containing neolacto-series glycolipid was found to accumulate in association with aging and cataract progression, the sialyl-Lewisx gangliosides did not show much accumulation in individual lenses from subjects between 16 and 80 years old. The content of sialyl-Lewisx gangliosides was about two to four times higher than that of Lewisx glycolipids, suggesting the possibility that the increase in Le(x) glycolipid is partly due to the desialylation of sialyl-Le(x) gangliosides. On the other hand, the expression of ganglio-series gangliosides increased in an age-related manner. Thus, age-related changes in lens glycolipids may modify the cell-to-cell interaction induced by cell surface sugar chains, leading to the initiation and progression of cataract. PMID- 7789412 TI - Age-related response of human lenses to stretching forces. AB - Five human lenses of varying ages were subjected to radial stretching forces which mimic the action of the ciliary muscle in vivo. Although the number of lenses was small, it was found that the human lens becomes more resistant, with age, to radial stretching forces and that lenses over the age of 50 years showed very little response to stretch. In prepresbyopic lenses, stretching has a greater effect on the shape of the anterior surface than it does on the shape of the posterior surface. The five lenses studied showed individual variations in lens size and shape and a trend to increased curvature with age, particularly marked for the anterior surface. PMID- 7789413 TI - Evidence of a difference in photoreceptor cell loss in the peripheral versus posterior regions of the vitiligo (C57BL/6J-mi(vit)/mi(vit)) mouse retina. PMID- 7789414 TI - Effect of the topical application of nitroglycerin on intraocular pressure in normal and glaucomatous monkeys. PMID- 7789415 TI - Characterization of native pathogenic antigens of Onchocerca volvulus: identification of high molecular mass protein antigens eliciting interstitial keratitis in a guinea pig model. AB - Sclerosing keratitis is the predominant cause of blindness due to onchocerciasis which is a major human parasitic disease caused by the filarial parasite Onchocerca volvulus. In the present investigation, native pathogenic antigens of O. volvulus which are particularly potent in causing interstitial keratitis were characterized utilizing a guinea pig model. Following demonstration of the protein nature of these antigens using pronase digestion, the crude O. volvulus antigen extract was subjected to stepwise procedures of protein purification. At each stage of purification, pooled antigen fractions were injected into one cornea of presensitized guinea pigs followed by clinical evaluation of stromal inflammation and vascularization at different intervals of time after intrastromal challenge. Initial purification of the pathogenic antigens was carried out in the following order: molecular sieve chromatography on Bio-gel A 5m. anion exchange chromatography on Mono Q followed by DEAE-Sepharose CL-6B and cation exchange chromatography on Mono S. Two out of six different pools from the Mono S column (pool a eluted unbound at 10 mM-NaCl and pool e eluted between 130 mM and 475 mM-NaCl) were found to be most pathogenic. Further purification of Mono S pool a and pool e separately by gel filtration chromatography using Superose 12 demonstrated that the fractions which were most potent in inducing interstitial keratitis contained proteins with approximate molecular masses between 100 and 200 kDa. These results show that minor subfractions of total crude antigens of O. volvulus are largely responsible for induction of experimental interstitial keratitis. We have demonstrated the presence of these antigens in O. volvulus microfilariae by their cross-reactivities with anti microfilarial antibodies, and hence the relevance of the purified antigens to ocular onchocerciasis in man since sclerosing keratitis is associated with invasion of the cornea by O. volvulus microfilariae. Isolation of these two pathogenic antigen pools represents the practical limits of purification and subsequent animal experiments possible with the available amounts of native parasite material obtained from infected human individuals in the absence of a suitable non-human host or of an in vitro culture system for O. volvulus. PMID- 7789416 TI - Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. AB - The purpose of the present study was to selectively target pigmented trabecular meshwork cells without producing collateral damage to adjacent non-pigmented cells or structures. The ability to selectively target trabecular meshwork cells without coagulation, while preserving the structural integrity of the meshwork, could be a useful approach to study whether the biological response of non coagulative damage to the trabecular meshwork and trabecular meshwork cells is similar to that seen with coagulative damage to the trabecular meshwork which occurs with argon laser trabeculoplasty. This approach also may be useful to non invasively deplete trabecular meshwork cells while preserving the structural integrity of the trabecular meshwork in an animal model. A mixed cell culture of pigmented and non-pigmented trabecular meshwork cells were irradiated with Q switched Nd-YAG and frequency-doubled Nd-YAG lasers, microsound pulsed dye lasers, and an argon ion laser in order to define a regime where laser absorption would be confined to pigmented trabecular meshwork cells, thereby permitting selective targeting of these cells without producing collateral thermal damage to adjacent non-pigmented cells. Pulse durations ranged from 10 nsec to 0.1 sec. A fluorescent viability/cytotoxicity assay was used to evaluate laser effects and threshold energies, and cells were examined morphologically by light and TEM. Selective targeting of pigmented trabecular meshwork cells was achieved with pulse durations between 10 nsec and 1 microsec and 1 microsec without producing collateral thermal or structural damage to adjacent non-pigmented trabecular meshworks cells when examined by light and transmission electron microscopy. Pulse durations greater than 1 microsec resulted in non-selective killing of non pigmented trabecular meshwork cells. Threshold radiant exposures were as low as 18 mJ cm-2, and increased at longer wavelengths, longer pulse durations and lower melanin contents within the cells. It is concluded that selective targeting of pigmented trabecular meshwork cells can be achieved using pulsed lasers with low threshold radiant exposures avoiding collateral thermal damage to adjacent non pigmented trabecular meshwork cells. This approach can be readily applied in vivo. PMID- 7789417 TI - Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon. AB - A new apparatus has been developed using the laser speckle phenomenon for non contact, two-dimensional analysis of tissue circulation in the choroid and optic nerve head (ONH). The fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB), which is a quantitative index of blood velocity. The results were displayed on color graphic monitors showing the two-dimensional variation of the NB level in the measurement field. In the rabbit, this apparatus was used to study the relationship between the results of NB measurement and the choroidal blood flow determined by the microsphere technique, the relationship between NB obtained from the ONH tissue free of visible surface vessels and the ocular perfusion pressure (OPP) after a lethal injection of pentobarital, and the effect of intraocular pressure (IOP) on the NB in the choroid or in the ONH. A stepwise reduction in the OPP was introduced by elevating the IOP manometrically. The relative decrease in the average NB over the field measured, NBav, in the choroid with the reduction in OPP showed a significant correlation with the relative change in the blood flow rate determined using the microsphere technique (r = 0.60, P < 0.001). NBav in the ONH had a good correlation with the OPP after a lethal injection of pentobarbital (r = 0.98, P < 0.001). NBav in the choroid decreased with reduction in the OPP. Although NBav in the ONH was little affected by OPP change when OPP was above 40 mmHg, at OPP levels below 40 mmHg, NBav in the ONH decreased along with a reduction in the OPP. These results suggest that by using the present apparatus, the blood velocity in the choroid or ONH under various conditions can be studied non-invasively in the living eye. PMID- 7789418 TI - Class III beta-tubulin in human retinal pigment epithelial cells in culture and in epiretinal membranes. AB - The class III beta-tubulin isotype (beta III) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in 1 day-old primary cultures; however, beta III is present in RPE cells in 5-day primary cultures and in passaged RPE cells grown in monolayer cultures as determined by immunohistochemistry and Western blotting. beta III-positivity in cultured RPE cells is not affected by cell density or hydroxyurea- or retinoic-acid-mediated growth inhibition, but only a few cells weakly express beta III in cyclohexamide-treated cultures and RPE cells maintained in serum-free medium fail to produce beta III. When monolayer-cultured RPE cells grown in normal, serum-containing medium, are transferred to irradiated bovine vitreous, beta III is undetectable in most cells. Cultured RPE cells coexpress beta III with keratin and cellular retinaldehyde-binding protein (both RPE cell markers), but not with glial fibrillary acidic protein. Some cultured RPE cells also express neuron-specific (gamma) enolase, which is neuron associated but not neuron-specific, and occasional cells in confluent or super confluent cultures contain the 200-kDa neurofilament protein. Retinal glia, fibroblasts, endothelial cells, and smooth muscle cells do not express beta III under the same culture conditions. We have detected beta III in 45 of 56 epiretinal membranes, frequently in cells with a bipolar or dedifferentiated morphology, where its expression coincides with other RPE cell-associated antigens. Cells with morphological features resembling normal RPE cells in epiretinal membranes are usually negative for beta III, but RPE cells appearing to be in the early stages of dedifferentiation express the isotype weakly. Electron microscopic immunocytochemistry localizes beta III to microtubules, ribosomes and cytoplasm. beta III may be a useful marker for recognizing the fraction of RPE cells in epiretinal membranes that are no longer identifiable by morphological criteria or other RPE cell markers. These findings demonstrate that mature human RPE cells have the capacity to express a neuron-associated gene in response to conditions that promote dedifferentiation. PMID- 7789419 TI - Alternative splicing in human retinal mRNA transcripts of an opsin-related protein. AB - An opsin-related gene encodes a putative RPE-retinal G-protein-coupled receptor (RGR) that is most homologous to the visual pigments and invertebrate retinochrome. A splice variant of human RGR mRNA can be demonstrated by the sequence of isolated cDNA clones and by the amplification and analysis of human retinal mRNA. The shortened transcript contains a deletion of 114 nucleotides that correspond exactly to the sequence of exon 6 in the human rgr gene. The predicted RGR variant lacks the putative sixth transmembrane domain and has a calculated molecular weight of 27,726. Variable amounts of a 28-kDa protein were found in the retinas of some individuals by immunoblot assay. Since a similar shortened RGR transcript was not detected in bovine retina or RPE, the RGR variant is not essential for vertebrate vision. Analysis of the structure of the rgr gene and of the sequences of cDNA clones indicates that the truncated mRNA may be produced through alternative splicing of pre-mRNA from which a cassette exon is removed and the predicted RGR variant is radically altered in primary structure. PMID- 7789420 TI - Variations in refractive index and absorbance of 670-nm light with age and cataract formation in human lenses. AB - A newly-developed fibre-optic sensor (wavelength of 670 nm) was used to measure the index gradient in 16 human lenses ranging in age from 38 to 78 years. Two of these lenses had nuclear cataract. The refractive index, calculated from the proportion of reflected light at the sensor/sample interface, appeared to increase with age and further with cataract formation. This was not consistent with previous studies. The increased losses of reflected light, which gave apparent increased values of refractive index, were reconsidered to be resulting from light absorption and an estimate of relative absorption was made by deducting excess light loss from a base level expected to yield the maximum index value. The characteristics of the relative absorption are similar to those of a red fluorophor reported in other studies. PMID- 7789421 TI - Oxygen modulates production of bFGF and TGF-beta by retinal cells in vitro. AB - Vasoproliferative retinopathies result from retinal capillary non-perfusion and consequent inner retinal hypoxia. However, it is not known whether oxygen mediates vasoproliferation directly (at the nuclear level) or indirectly by regulating the production of growth factors. We have investigated the effect of oxygen on the production of basic fibroblast growth factor and transforming growth-factor-beta by a variety of retinal cell types in culture. Confluent cultures were maintained for 48 hr under varying oxygen tensions ranging from 135 to 18 mmHg. A reduction in basic fibroblast growth factor levels was observed in the cell lysates and extracellular matrix from retinal microvascular endothelial cell, retinal microvascular pericyte and retinal pigment epithelial cell cultures when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Levels of basic fibroblast growth factor in conditioned media from microvascular endothelial and retinal pigment epithelial cell cultures also decreased when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Total transforming growth-factor-beta (and specifically isoforms 1 and 2) in the conditioned media from all three cell types was similarly modulated by oxygen i.e. it decreased as the oxygen tension of the medium was reduced from 135 to 18 mmHg. In contrast, the steady state messenger RNA levels for both basic fibroblast growth factor and transforming-growth-factor-beta 1 genes in RPE cells increased significantly when the oxygen tension of the medium was reduced from 135 to 18 mmHg. These results support the putative role of oxygen in influencing the balance of growth factors during the development of preretinal new vessels. PMID- 7789422 TI - Effect of acetazolamide on intracellular pH and bicarbonate transport in bovine corneal endothelium. AB - Carbonic anhydrase inhibitors are known to inhibit fluid transport by the corneal endothelium. This phenomenon could be due to a combination of effects involving disruption of intracellular pH regulation, reduced gradients for diffusion of CO2, substrate limitation to HCO3- transport systems or direct inhibition of membrane HCO3- transport. We examined the effects of the carbonic anhydrase inhibitor, Acetazolamide (ACTZ), on intracellular pH (pHi) and HCO3- transport in cultured bovine corneal endothelium. The pHi was measured utilizing the pH sensitive fluorescent dye, BCECF. Na+:HCO3- cotransport and Cl-/HCO3- exchange activities were studied by measuring the HCO3(-)-dependent flux of Na+ and Cl-, respectively. Na+ and Cl- fluxes were measured using the ion-sensitive dyes SBFI and SPQ, respectively. Application of 100 or 500 microM ACTZ to cells perfused under HCO3(-)-rich conditions, significantly reduced steady-state pHi by 0.06 +/- 0.01 (n = 14, P < 0.05). ACTZ also eliminated rapid pHi transients due to CO2 diffusion, significantly slowed the initial rate of pHi changes (50 +/- 10% of control, n = 7, P < 0.05) secondary to Na+:HCO3- cotransport or Cl-/HCO3- exchange (37 +/- 1% of control, P < 0.05, n = 7). However, the flux of the cotransported ions, Na+ and Cl-, and the steady-state levels of these ions were not affected by ACTZ. We conclude that the drop in steady-state pHi, the elimination of CO2 induced pHi transients and the slowed pHi changes secondary to HCO3- transport were due to inhibition of cytosolic carbonic anhydrase by ACTZ, i.e. slowing the equilibrium among CO2, HCO3- and H+ and not due to limitation of substrate availability or direct inhibition of the membrane transporters. PMID- 7789423 TI - Regulation of retinal glial cell proliferation by antiproliferative molecules. AB - Glial cells normally do not proliferate in the adult retina despite the presence of glial mitogens. In this study, we examined the hypothesis that endogenous antiproliferative molecules inhibit the effects of glial mitogens. Using cultures of glial cells obtained from the adult human retina, we found that transforming growth factor beta 2 (TGF beta 2) and a metabotrophic glutamate agonist (t-ACPD) inhibit the mitogenic effects of basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor and insulin-like growth factor-1. These antiproliferative effects may involve activation of protein kinase C (PKC) since chelerythine, a specific PKC inhibitor, blocks the antiproliferative effects of TGF beta 2 and t-ACPD. Furthermore, exposure of the glia to a phorbol ester mimics the inhibitory effects of TGF beta 2 or t-ACPD. Although TGF beta 2 and t ACPD markedly inhibit a number of mitogens, they do not alter the mitogenic response of retinal glia to thrombin and glutamate. A common characteristic of the mitogens sensitive to TGF beta 2 or t-ACPD is activation of tyrosine kinase linked receptors. In contrast, thrombin acts at a G-protein-linked receptor, and glutamate stimulates retinal glial proliferation via activation of an NMDA receptor. It appears that TGF beta 2 and t-ACPD may selectively inhibit retinal glial mitogenesis mediated by activation of tyrosine kinase-linked receptors. Our experiments support the idea that endogenous antiproliferative molecules play a role in preventing glial proliferation in the retina. PMID- 7789425 TI - Large optic discs in large eyes, small optic discs in small eyes. AB - The optic disc area, varying interindividually by a factor of 1:7, is correlated with the count of the retinal ganglion cell axons and photoreceptors. This study evaluated whether the variations in the disc size are additionally correlated with those of the coronary diameters of the globe. Fifty-three normal human donor eyes with a mean age of 54.2 +/- 19.6 years were included in the study. After performing a 16-mm corneoscleral trephination, the globes were fixed and the horizontal and vertical diameters of the globes were measured. We cut the globes into meridional slices sticking together at the posterior fundus region. The areas of the whole retina and the optic disc were planimetrically evaluated on photographs with a millimeter scale aligned. We found that the horizontal and vertical diameters of the globe were correlated with the optic disc size and the retinal surface area. Eyes with long horizontal and vertical diameters had a larger optic disc and a larger retinal surface area than eyes with short diameters. The results suggest the combination of large optic discs in large eyes and of small optic discs in small eyes. Taking into account the relatively low correlation coefficients of 0.3 and 0.4, the study also suggests the existence of other not-evaluated factors influencing the occurrence of large optic discs. The results go along with the reported association between a large optic disc area and a large cornea size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789426 TI - Relationship between the organization of the forepaw barrel subfield and the representation of the forepaw in layer IV of rat somatosensory cortex. AB - We studied the organization of the forepaw barrel subfield (FBS) in layer IV of adult rat somatosensory cortex using the mitochondrial marker cytochrome oxidase and related this organization to the representation of the forepaw. The FBS is an ovoid structure consisting of barrels and barrel-like structures, the most conspicuous of which form four centrally located medio lateral running bands. Each band contains three to four barrels. These centrally located bands are bordered along their entire lateral side by a nebulous zone of undifferentiated labeling. At the anterior border, two small barrels are located laterally and one or two larger barrels are located medially. Medial to the central zone are three well-defined barrels. The posterior border consists of a nebulous field of labeling and occasional barrel-like structures. The results from our electrophysiological recording and mapping revealed that the forepaw representation was topographically organized into a single map and that the forepaw map matches almost precisely with individual barrels and barrel-like structures in the FBS. Each of the four central bands is associated with the representation of a single glabrous digit. Digit two (D2) is represented anteriorly and followed posteriorly by D3 through D5. Within each digit band the digit is somatotopically organized, with the skin over the distal phalanx represented in the two lateral barrels and the middle and proximal phalanges represented in the medial barrel(s). The dorsal hairy digit skin and dorsal hand are represented in the lateral zone. D1 is represented by two small anteriorly located barrels. Medial to the representation of the glabrous digits is the representation of the palmar pads. The representation of these pads, in turn, lies between the representations of the thenar (located anteriorly) and hypothenar (located posteriorly) pads. Posterior to the hypothenar pad representation lie the representations of the wrist and forearm. While the present results support the conclusion that individual barrels are associated with discrete locations on the forepaw, examples were found where the recording site was not precisely located within the predicted barrel. Some of these errors may be accounted for by limitations in the mapping techniques; nevertheless, the FBS offers an excellent model system to study relationships between cortical structure and function. PMID- 7789424 TI - Distribution of F-actin, vinculin and integrin subunits (alpha 6 and beta 4) in response to corneal substrata. AB - Our goal was to determine the early response of corneal epithelial cells to living modified stromal substrates. We examined the distribution of integrin subunits (alpha 6 and beta 4), vinculin and the organization of F-actin in epithelial cells after cell-matrix and cell-cell hypothesized that the distribution of proteins in the cell matrix attachment complex would be altered if the substrate was modified. Integrin subunits, alpha 6 and beta 4, were chosen as they play a role in cell matrix adhesion and adhesion site formation. Corneal epithelial cells were cultured from explants and seeded on three corneal substrates (a stroma containing an intact basal lamina, a cornea lacking a basal lamina and a cornea treated with alkali). After 3 h of incubation, the tissue was fixed and stained with monoclonal antibodies specific for vinculin and for the integrin subunits alpha 6 and beta 4. The organization of F-actin was assessed using rhodamine phalloidin. The localization of the proteins was recorded with confocal laser scanning microscopy. Filamentous actin delineated the lateral cell membranes of corneal epithelial cells. The organization of actin and distribution of vinculin and integrin subunits of epithelial cells cultured on stromal substrates containing a basal lamina mimicked a simple epithelial organization. In contrast, when cells are cultured on the substrate lacking a basal lamina and alkaline treated corneal substrates the distribution of the specific proteins examined was altered. Vinculin and alpha 6 were present along membranes of cells cultured on substrates lacking a basal lamina and were diffuse in cells cultured on the alkaline substrates. These studies demonstrate that changes in the distribution of adhesion and cytoskeletal proteins in response to different surfaces may contribute to the healing dynamics in different wounds. PMID- 7789428 TI - Express saccades in cat: effects of task and target modality. AB - Saccadic eye movements to visual, auditory, and bimodal targets were measured in four adult cats. Bimodal targets were visual and auditory stimuli presented simultaneously at the same location. Three behavioral tasks were used: a fixation task and two saccadic tracking tasks (gap and overlap task). In the fixation task, a sensory stimulus was presented at a randomly selected location, and the saccade to fixate that stimulus was measured. In the gap and overlap tasks, a second target (hereafter called the saccade target) was presented after the cat had fixated the first target. In the gap task, the fixation target was switched off before the saccade target was turned on; in the overlap task, the saccade target was presented before the fixation target was switched off. All tasks required the cats to redirect their gaze toward the target (within a specified degree of accuracy) within 500 ms of target onset, and in all tasks target positions were varied randomly over five possible locations along the horizontal meridian within the cat's oculomotor range. In the gap task, a significantly greater proportion of saccadic reaction times (SRTs) were less than 125 ms, and mean SRTs were significantly shorter than in the fixation task. With visual targets, saccade latencies were significantly shorter in the gap task than in the overlap task, while, with bimodal targets, saccade latencies were similar in the gap and overlap tasks. On the fixation task, SRTs to auditory targets were longer than those to either visual or bimodal targets, but on the gap task, SRTs to auditory targets were shorter than those to visual or bimodal targets. Thus, SRTs reflected an interaction between target modality and task. Because target locations were unpredictable, these results demonstrate that cats, as well as primates, can produce very short latency goal-directed saccades. PMID- 7789427 TI - Saccade-related Purkinje cell activity in the oculomotor vermis during spontaneous eye movements in light and darkness. AB - Saccade-related Purkinje cells (PCs) were recorded in the oculomotor vermis (lobules VI, VII) during spontaneous eye movements and fast phases of optokinetic and vestibular nystagmus in the light and darkness, from two macaque monkeys. All neurons (n = 46) were spontaneously active and exhibited a saccade-related change of activity with all saccades and fast phases of nystagmus. Four types of neurons were found: most neurons (n = 31) exhibited a saccade-related burst of activity only (VBN); other units (n = 7) showed a burst of activity with a subsequent pause (VBPN); some of the units (n = 5) paused in relation to the saccadic eye movement (pause units, VPN); a few PCs (n = 3) showed a burst of activity in one direction and a pause of activity in the opposite direction. For all neurons, burst activity varied considerably for similar saccades. There were no activity differences between spontaneous saccades and vestibular or optokinetically elicited fast phases of nystagmus. The activity before, during, and after horizontal saccades was quantitatively analyzed. For 24 burst PCs (VBN, VBPN), the burst started before saccade onset in one horizontal direction (preferred direction), on average by 15.3 ms (range 27-5 ms). For all these neurons, burst activity started later in the opposite (non-preferred) direction, on average 4.9 ms (range 20 to -12 ms, P < 0.01) before saccade onset. The preferred direction could be either with ipsilateral (42% of neurons) or contralateral (58%) saccades. Nine burst PCs had similar latencies and burst patterns in both horizontal directions. The onset of burst activity of a minority of PCs (n = 5) lagged saccade onset in all directions. The pause for VBPN neurons started after the end of the saccade and reached a minimum of activity some 40-50 ms after saccade completion. For all saccades and quick phases of nystagmus, burst duration increased with saccade duration. Peak burst activity was not correlated with saccade amplitude or peak eye velocity. PCs continued to show saccade related burst activity in the dark. However, in 59% of the PCs (VBN, VBPN), peak burst activity was significantly reduced in the dark (on average 28%, range 15 36%) when saccades with the same amplitude (but longer duration in the dark) were compared. For VBP neurons, the pause component after the saccade disappeared in the dark.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789429 TI - Kinematic analysis of wing and leg movements for type I motility in E9 chick embryos. AB - Based on studies using direct observation methods, type I motility, the first motility pattern to emerge in chick embryos, is characterized as random, uncoordinated movement. Yet, electromyographic (EMG) studies indicate that leg muscles are recruited in orderly patterns of alternating flexor and extensor activity during type I motility. It has been suggested that this apparent paradox may be attributable to perturbations arising during movement in ovo under buoyant conditions. It is also possible that direct observation methods are insufficient to detect the extent of coordination between body parts during type I motility. To address the apparent discrepancy between random features reported in observational studies and reliable features reported in EMG studies, embryos were video recorded continuously for 60 min at embryonic day 9 and criteria were established to obtain homogeneous samples of motility for kinematic analysis of synchronous wing and leg movements. Limited to a single camera attached to a stereomicroscope, methods were developed to correct for out-of-plane movements of the ipsilateral wing and leg. Also, amniotic fluid was extracted from the egg in some recordings to test the possibility that movement under buoyant conditions may mask coordinated movement. Extended sequences of activity were digitized and analyzed. Results indicated that within a limb (wing or leg), direction and timing of excursions at adjacent joints co-varied and limb excursions were characterized by reliable patterns of alternating flexion and extension consistent with EMG studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789430 TI - Effects of eye position on saccadic eye movements and on the neuronal responses to auditory and visual stimuli in cat superior colliculus. AB - Many neurons in the deeper layers of the superior colliculus (SC) respond to multiple sensory inputs--visual, auditory, and somatic--as well as provide signals essential for saccadic eye movements to targets in different modalities. When the eyes and pinnae are in primary position, the neural map of auditory space is in rough topographic alignment with the map of visual space, and if the auditory map is based solely on headpinna coordinates, any changes in eye position in the orbit will cause misalignment of the maps. We investigated the effects of eye position on the response of sound-sensitive neurons in the SC of cats because previous work on cats and on monkeys had suggested the possibility of species differences in the representation of auditory signals in the SC. We also investigated the effects of eye position on the accuracy of saccades to auditory, visual, and bimodal stimuli. All studies were conducted in alert, trained cats with the head restrained in a fixed position. Neuronal and behavioral responses were studied during periods when the eyes were steadily directed to different positions relative to the position of the sound. Cats showed partial compensation for eye position in making saccades, regardless of the modality of the target, and they showed similar patterns of error in saccades to auditory and visual targets. These behavioral data are consistent with coding the location of visual and auditory targets in the same coordinate system. In the vast majority of intermediate-layer neurons, eye position significantly affected the number of spikes evoked by sound stimuli. For most of these neurons, changes in eye position produced significant shifts in the speaker location producing maximal response. In some neurons, eye position significantly facilitated the magnitude of neuronal response evoked by sounds from a variety of speaker locations. Because few pinna movements could be detected, in is unlikely that these changes in neuronal response could be due to changes in the position of the pinnae. Our results indicate that the deep layers of the SC contain an eye centered representation of sound location. Because eye position did not affect the percentage of neurons exhibiting multimodal integration, visual and auditory maps appear to remain integrated in the SC even when the eyes are directed eccentrically.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789431 TI - Nerve injury in adult rats causes abnormalities in the motoneuron dendritic field that differ from those seen following neonatal nerve injury. AB - Disruption of neuromuscular contact by nerve-crush during the early postnatal period causes increased activity and abnormal reflex responses in affected motoneurons, but such changes are not found after nerve-crush in adult animals. We found previously that neonatally lesioned cells develop an abnormal dendritic field, which may explain the functional changes. Here we have studied the dendritic morphology of the same motoneuron pool after nerve-crush at maturity in order to correlate the observed alterations in morphology with physiological findings. One to two months after sciatic nerve-crush in adult animals, motoneurons supplying the extensor hallucis longus muscles of the rat were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase. The dendritic tree of labelled cells was then analysed. Following adult nerve-crush, the dendritic tree of the motoneurons was smaller but did not display the localised increase in dendritic density seen after neonatal nerve crush. These findings support the view that such specific morphological changes contribute to the physiological abnormalities seen only after neonatal nerve injury. PMID- 7789432 TI - Cross-correlation of augmenting expiratory neurons of the Botzinger complex in the cat. AB - Ipsilateral and contralateral pairs of augmenting expiratory neurons were recorded simultaneously from the Botzinger complex using glass-coated tungsten microelectrodes in pentobarbitone-anaesthetized cats. The neurons were identified both by firing pattern and by antidromic activation from the contralateral site of the dorsal respiratory group. Cross-correlation histograms of the extracellularly recorded action potentials were calculated in order to detect short time-scale synchronizations of firing indicative of synaptic connections between the neurons. The cross-correlation histograms for 40 ipsilateral pairs of neurons less than 1 mm apart showed eight (20%) narrow troughs (mean half amplitude width +/- SD, 1.1 +/- 0.37 ms) at short latencies (mean latency +/- SD, 1.0 +/- 0.35 ms) suggestive of monosynaptic inhibition. These included two cross correlation histograms which showed troughs on both sides of time zero, indicating a mutual inhibition. For another four pairs of neurons (10%), a central broad peak suggestive of common activation due to either excitation or release from inhibition was evident. Contralateral pairs of expiratory neurons of the Botzinger complex were examined in a similar manner. The cross-correlation histograms for 43 pairs of neurons showed five (12%) narrow troughs (mean half amplitude width +/- SD, 1.2 +/- 0.67 ms) at short latencies (mean latency +/- SD, 2.7 +/- 1.47 ms) suggestive of monosynaptic inhibition. These included one cross correlation histogram which showed troughs (one not statistically significant) on both sides of time zero, indicating a mutual inhibition. For another two pairs of neurons (4.6%) a central, broad peak suggestive of common activation due to either excitation or release from inhibition was evident. We conclude that inhibitory interconnections exist between augmenting expiratory neurons of the Botzinger complex ipsilaterally and contralaterally. These connections may synchronize the expiratory burst of activity within this population and assist in the patterning of the burst. PMID- 7789433 TI - Human eye movement response to z-axis linear acceleration: the effect of varying the phase relationships between visual and vestibular inputs. AB - We investigated the effect of systematically varying the phase relationship between 0.5-Hz sinusoidal z-axis optokinetic (OKN) and linear acceleration stimuli upon the resulting vertical eye movement responses of five humans. Subjects lay supine on a linear sled which accelerated them sinusoidally along their z-axis at 0.4 g peak acceleration (peak velocity 1.25 m/s). A high contrast, striped z-axis OKN stimulus moving sinusoidally at 0.5 Hz, 70 degrees/s peak velocity was presented either concurrently or with the acceleration stimulus or alone. Subjects' vertical eye movements were recorded using scleral search coils. When stimuli were paired in the naturally occurring relationship (e.g., visual stripes moving upward paired with downward physical acceleration), the response was enhanced over the response to the visual stimulus presented alone. When the stimuli were opposed (e.g., visual stripes moving upward during upward physical acceleration, a combination that does not occur naturally), the response was not significantly different from the response to the visual stimulus presented alone. Enhancement was maximized when the velocities of the visual and motion stimuli were in their normal phase relationship, while the response took intermediate values for other phase relationships. The phase of the response depended upon the phase difference between the two inputs. We suggest that linear self-motion processing looks at agreement between the two stimuli-a sensory conflict model. PMID- 7789434 TI - The role of haptic cues from rough and slippery surfaces in human postural control. AB - Haptic information is critically important in complex sensory-motor tasks such as manipulating objects. Its comparable importance in spatial orientation is only beginning to be recognized. We have shown that postural sway in humans is significantly reduced by lightly touching a stable surface with a fingertip at contact force levels far below those physically necessary to stabilize the body. To investigate further the functional relationship between contact forces at the hand and postural equilibrium, we had subjects stand in the tandem Romberg stance while being allowed physically supportive (force contact) and non-physically supportive (touch contact) amounts of index fingertip force on surfaces with different frictional characteristics. Mean sway amplitude (MSA) was reduced by over 50% with both touch and force contact of the fingertip, compared to standing without fingertip contact. No differences in MSA were observed when touching rough or slippery surfaces. The amplitude of EMG activity in the peroneal muscles and the timing relationships between fingertip forces, body sway and EMG activity suggested that with touch contact of the finger or with force contact on a slippery surface long-loop "reflexes" involving postural muscles were stabilizing sway. With force contact of the fingertip on a rough surface, MSA reduction was achieved primarily through physical support of the body. This pattern of results indicates that light touch contact cues from the fingertip in conjunction with proprioceptive signals about arm configuration are providing information about body sway that can be used to reduce MSA through postural muscle activation. PMID- 7789435 TI - Timing of finger opening and ball release in fast and accurate overarm throws. AB - How precisely does the CNS control the timing of finger muscle contractions in skilled movements? For overarm throwing, it has been calculated that a ball release window of less than 1 ms is needed for accuracy in long throws. The objective was to investigate the timing precision of ball release and finge opening for 100 overarm throws made using only the arm. Subjects sat with a fixed trunk and threw balls fast and accurately at a 6-cm-square target when it was 1.5, 3.0 and 4.5 m away. Three-dimensional angular positions in space of the clavicle, upper arm, forearm, hand and distal phalanx of the middle finger were simultaneously recorded at 1000 Hz using the magnetic-field search-coil technique. Ball release was determined by pressure-sensitive microswitches on the proximal and distal phalanges of the middle finger (proximal and distal triggers). Variability of ball release, defined in terms of the standard deviation (SD) of the means of release times, was different when synchronized to different hand kinematic parameters. It was highest to the start of movement (when the hand started rotating vertically forward and up around a space-fixed horizontal axis) and was lowest when synchronized to the moment near ball release when the hand was vertical. These values did not depend on target distance. When throws were synchronized to vertical hand position, and SDs were averaged across the 10 subjects, the average interval for 95% of the throws (4xSD) was 9.6 ms for ball release and 10.0 ms for onset of finger opening. Thus, two independent measures of timing precision gave similar results. It is concluded that for 100 fast and accurate throws made by male recreational ball players, timing of finger opening and ball release was controlled precisely but not to fractions of a millisecond. PMID- 7789436 TI - Effects of warning signals and fixation point offsets on the latencies of pro- versus antisaccades: implications for an interpretation of the gap effect. AB - The present study was designed to evaluate whether fixation point offsets have the same effects on the average latencies of prosaccades (responses towards target) and antisaccades (responses away from target). Gap and overlap conditions were run with and without an acoustic warning signal. The 'gap effect' was taken to be the difference in mean reaction time between gap and overlap trials. This effect was dramatically reduced by the presentation of the warning signal. Without this signal, fixation offsets can serve as warning signals themselves, which artifactually inflates the magnitude of the gap effect. The warning effect of fixation offsets was equivalent for pro and antisaccades. A significant gap effect is still evident with the acoustic warning signal; however, in this case it is associated primarily with prosaccades. These results replicate and extend our previous work demonstrating that, if their warning effects are controlled, the facilitatory effects of fixation point offsets are response dependent, and suggesting the existence of a component process (fixation release) which is closely linked with the processing architecture underlying target-directed saccades. PMID- 7789437 TI - Independent contributions of the orienting of attention, fixation offset and bilateral stimulation on human saccadic latencies. AB - In a series of experiments we examined the effects of the endogenous orienting of visual attention on human saccade latency. Three separate manipulations were performed: the orienting of visual attention, the prior offset of fixation (gap paradigm) and the bilateral presentation of saccade targets. Each of these manipulations was shown to make an independent contribution to saccade latency. In experiments 1 and 2 subjects were instructed to orient their attention covertly to a location by a verbal pre-cue; targets could appear in the attended hemifield (valid) or in the non-attended hemifield (invalid) together with a no instruction (neutral) condition. Saccades were made under fixation gap and overlap conditions, to either single target or two bilaterally presented targets which appeared at equal and opposite eccentricities in both hemifields. The results showed a large increase (cost) of saccade latency to invalid targets and a small non-significant decrease (benefit) of saccade latency to valid targets. The cost associated with invalid targets replicates the "meridan crossing effect" shown in manual reaction time experiments and is consistent with the hemifield inhibition and premotor models of attentional orienting. The use of a "gap" procedure produced a generalised facilitation of saccade latency, which was not modified by the prior orienting of visual attention. The magnitude of the gap effect was similar for saccades made to attended and non-attended stimulis. This suggests that the gap effect may be due to ocular motor disengagement, or a warning signal effect, rather than to the prior disengagement of visual attention. When two targets were presented simultaneously, one in each hemifield, saccade latency was slowed compared with the single target condition. The magnitude of this slowing was unaffected by the prior orienting of visual attention or by the fixation condition. The slowing was examined in more detail in experiment 3, by presenting targets with brief offset delays. The latency increase was maximal if the two targets were presented simultaneously and decreased if the distractor appeared at short intervals (20-80 ms) before or after the saccade target onset. If the non-attended stimulus was presented at greater intervals (160, 240 ms) before the saccade target, then a facilitation effect was observed. This demonstrates that the onset of a distractor in the non attended hemifield can have both an inhibitory and a facilitatory effect on a saccade production. PMID- 7789438 TI - Oculo-manual coordination control: respective role of visual and non-visual information in ocular tracking of self-moved targets. AB - We evaluated the role of visual and non-visual information in the control of smooth pursuit movements during tracking of a self-moved target. Previous works have shown that self-moved target tracking is characterised by shorter smooth pursuit latency and higher maximal velocity than eye-alone tracking. In fact, when a subject tracks a visual target controlled by his own arm, eye movement and arm movement are closely synchronised. In the present study, we showed that, in a condition where the direction of motion of a self-moved visual target was opposite to that of the arm (same amplitude, same velocity, but opposite direction of movement), the resulting smooth pursuit eye movements occurred with low latency, and continued for about 140 ms in the direction of the arm movement rather than in the direction of the actual visual target movement. After 140 ms, the eye movement direction reversed through a combination of smooth pursuit and saccades. Subsequently, while arm and visual target still moved in opposite directions, smooth pursuit occurred in pace with the visual target motion. Subjects were also submitted to a series of 60 tracking trials, for which the arm to-target motion relationship was systematically reversed. Under these conditions subjects were able to initiate early smooth pursuit in the actual direction of the visual target. Overall, these results confirm that non-visual information produced by the arm motor system can trigger and control smooth pursuit. They also demonstrate the plasticity of the neuronal network handling eye-arm coordination control. PMID- 7789439 TI - Directional specificity of postural muscles in feed-forward postural reactions during fast voluntary arm movements. AB - Healthy subjects performed bilateral fast shoulder movements in different directions while standing on a force platform. Anticipatory postural adjustments were seen as changes in the electrical activity of postural muscles as well as displacements of the center of pressure and center of gravity. Postural muscle pairs of agonist-antagonist commonly demonstrated triphasic patterns starting prior to the first electromyographic (EMG) burst in the prime-mover muscle. Proximal postural muscles demonstrated the largest anticipatory increase in the background activity during movements in one of the two opposite directions (forward or backwards). These changes progressively decreased when movements deviated from the preferred direction and frequently disappeared during movements in the opposite direction. The patterns in distal muscles varied across subjects and could demonstrate larger anticipatory changes during movements forward and backwards as compared to movements in intermediate directions. Bilateral addition of inertial loads to the wrists did not change the general anticipatory patterns, while making some of their features more pronounced. Anticipatory postural adjustments were followed by later changes in the activity of postural muscles, also reflected in the mechanical variables. Changes in leg joint angles revealed a "hip-ankle strategy" during shoulder flexions and an "ankle strategy" during shoulder extensions. The study demonstrates different behaviors of proximal and distal muscles during anticipatory postural adjustments in preparation for fast arm movements. We suggest that the proximal muscles produce a general pattern of postural adjustments, while distal muscles take care of fine adjustments that are more likely to vary across subjects. PMID- 7789440 TI - Influence of opioids and naloxone on rhythmic motor activity in spinal cats. AB - The effects of L-DOPA, naloxone, and the opioids (D-Ala2,N-Me-Phe4,Gly5-ol) enkephalin (DAGO) and D-Ser2-Leu-enkephalin-Thr6 (DSLET) on spinal motor rhythm generation were compared in anemically decapitated high spinal cats. After premedication with nialamide, DOPA caused the well-known, slow rhythmic motor activity with a locomotor pattern. The cycle duration of the evoked rhythm was usually between 3.9 and 5.0 s. The opioids DAGO and DSLET, injected intravenously (1.2-2 mg/kg) or suffused over the lumbar spinal cord (10(-3)-10(-4) M in Ringer's solution), severely depressed the DOPA-induced rhythmic activity, sometimes completely abolishing efferent motor activity. Naloxone (0.5-1 mg/kg i.v.) exerted different rhythm-facilitating effects, depending on the experimental condition. In the acute phase after spinalization, without paralysis and without nialamide and DOPA, naloxone induced rhythmic movements with a main frequency of 1.2-2 Hz. In the same preparation with paralysis, naloxone induced a rhythmic motor activity with a distinctly higher frequency (main range 4.3-5.8 Hz). After premedication with nialamide and DOPA, naloxone facilitated or, if a rhythm was absent, induced the slow-frequency DOPA type of rhythm. Given after i.v. or topical opioid application, naloxone antagonized the rhythm-depressing action of the opioid and caused an additional facilitation of rhythmic activity. Dopa and naloxone facilitated the long-latency, segmental reflex pathways from flexor reflex afferents (FRA), while the opioids depressed them. The short latency FRA pathways were depressed by DOPA and opioids but were facilitated by naloxone. The influence of the different drugs on spinal motor rhythm generation is discussed in relation to their influence on short- and long-latency segmental pathways from FRA. If the rhythm generation induced by DOPA is based on the release of the long-latency FRA pathways, as has been proposed before, the rhythm depressing action of opioids may be due to the suppression of these pathways, and the particular rhythm-generating function of naloxone may be related to its facilitation of short- and long-latency FRA pathways. PMID- 7789441 TI - Somatostatin-mRNA expression in brainstem projections into the medial preoptic nucleus. AB - The medial preoptic nucleus plays an important role in the regulation of neuroendocrine processes, vegetative functions, sexual behaviour and the modulation of the somatomotoric system. The connections of the medial preoptic nucleus to other areas of the central nervous system are very complex, and the area receives afferents using numerous transmitters and neuropeptides. Previous investigations have shown that this nucleus receives afferents from various brainstem nuclei that also contain somatostatinergic neurons. This study was carried out to investigate if somatostatin-projecting neurons of the brainstem are afferents to the medial preoptic nucleus. This was approached by combining somatostatin-mRNA in situ hybridisation with True Blue retrograde tracing. Our results demonstrate somatostinergic brainstem projections into the medial preoptic nucleus mainly in the pedunculopontine nucleus and in the nucleus of the solitary tract (50% together). Other important somatostatinergic afferents into the medial preoptic nucleus originate in the cuneiform area, the dorsal parabrachial nucleus and in the lateral reticular nucleus (37% together). Less important are the somatostatinergic projections coming from the central grey, the laterodorsal tegmental nucleus, the locus coeruleus and the nucleus raphe magnus. Considering that these areas are involved in diverse functions such as cardiovascular regulation (nucleus of the solitary tract), transmission of visceral sensibility (dorsal parabrachial nucleus), modulation of the somatomotoric system (pedunculopontine nucleus) and in the regulation of neuroendocrine mechanisms (locus coeruleus), it seems tenable that the somatostatin projections demonstrated here also have a diverse functional quality within the medical preoptic nucleus where they terminate. PMID- 7789442 TI - A comparison of the behavioural effects of embryonic nigral grafts in the caudate nucleus and in the putamen of marmosets with unilateral 6-OHDA lesions. AB - The behaviour of marmosets with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle and grafts of embryonic mesencephalon in either the caudate nucleus or the putamen was compared with that of lesion-alone and unoperated controls. The grafts comprised injections of cell suspensions prepared from marmoset ventral mesencephalon (i.e. allografts) targeted at four sites either entirely within the caudate nucleus or entirely within the putamen. Behavioural tests, including measures of amphetamine-induced rotation, neglect and use of each arm to retrieve food from inside tubes, were given before and after the 6 hydroxydopamine lesion and at regular intervals for 6 months after transplantation surgery. Grafts in the caudate nucleus reduced the ipsilateral rotation induced by amphetamine, whereas grafts in the putamen did not. Despite the absence of an effect on rotation, the putamen grafts were effective in reducing lesion-induced deficits on the task in which the marmosets were required to reach into tubes. In this latter task, the caudate grafts were also effective when the monkeys were given a free choice of which hand to use. However, when constrained to use the hand contralateral to the lesion and graft, the performance of the marmosets with caudate grafts was not significantly improved compared with that of lesion-alone controls. Neither the grafts in the caudate nucleus nor the grafts in the putamen abolished the contralateral somatosensory neglect induced by the lesion, although there was a trend for the marmosets with putamen grafts to contact the label on the contralateral side more quickly than those with caudate grafts or the lesion-alone controls. These results demonstrate that the location of embryonic nigral grafts within the primate striatum influences the profile of functional recovery. PMID- 7789443 TI - Brainstem modulation of signal transmission through the cat dorsal lateral geniculate nucleus. AB - We studied changes in retinogeniculate transmission that occur during variation of modulatory brainstem input and during variation of stimulus contrast. Responses of single cells in the dorsal lateral geniculate nucleus (dLGN) to a stationary flashing light spot of varying contrast were measured with and without electrical stimulation of the peribrachial region (PBR) of the brainstem. PBR stimulation increased the contrast gain (slope of response versus contrast curve) and the dynamic response range (range between spontaneous activity and maximal firing). Lagged and nonlagged X-cells reached the midpoint of the dynamic response range at lower contrasts during PBR stimulation than in the controls. No comparable change was seen for Y-cells. Only minor changes of threshold contrast were seen. The characteristics of the retinogeniculate transmission were directly studied by comparing the response of dLGN cells with their retinal input (slow potentials, S-potentials). With increasing contrast there was a marked increase in the transfer ratio (proportion of impulses in the input that generates action potentials in the dLGN cell). The transfer ratio seemed to be primarily determined by the firing rate of the retinal input. The transfer ratio increased with increasing input rates from low values near threshold to values that could approach 1 at high-input firing rates. PBR stimulation increased the transfer ratio, particularly at moderate input firing rates. The increased transfer ratio, caused by increasing input firing rates, enhanced the response versus contrast characteristics through an increase in contrast gain and dynamic response range. The modulatory input from the PBR further enhanced these characteristics. PMID- 7789444 TI - Electron microscopic study of synaptogenesis and myelination of the olfactory centers in developing rats. AB - Development of the central olfactory system was studied in the rat with an electron microscope at three main structures: the olfactory bulb, the lateral olfactory tract, and the primary olfactory cortex (the piriform cortex). As a parameter of development, the synaptic density was examined quantitatively in the bulbar glomerulus and layer Ia (termination of bulbofugal fibers) of the piriform cortex. which are the key stations of the olfactory pathway. The synaptic densities in the glomerulus and those in layer Ia were 5.7% and 4.6% on embryonic day 19, 15.8% and 12.5% on postnatal day (P) 0, and 57.3% and 37.2% on P10, as compared with the adult (100%). As another parameter of development, the density of myelinated axons in the lateral olfactory tract was examined quantitatively. The densities of myelinated axons in the tract were 0% on P5, 15.1% on P10, and 73.5% on P21 of the adult density. Maturation in the tract was still progressing, even at P21, in terms of bundle formation and the thickness of myelin sheaths. The results show that synaptogenesis in the bulbar glomerulus is followed by synaptogenesis in layer Ia of the piriform cortex, and that myelination in the lateral olfactory tract occurs over a prolonged period, even in the stages after P21. PMID- 7789445 TI - Influence of eye motion on adaptive modifications of the vestibulo-ocular reflex in the rat. AB - While sustained retinal slip is assumed to be the basic conditioning stimulus in adaptive modifications of the vestibulo-ocular reflex (VOR) gain, several observations suggest that eye motion-related signals might also be involved. We oscillated pigmented rats over periods of 20 min around the vertical axis, at 0.3 Hz and 20 degrees/s peak velocity, in different retinal slip and/or eye motion conditions in order to modify their VOR gain. The positions of both eyes were recorded by means of a phase-detection coil system with the head restrained. The main findings came from the comparison of two basic conditions--including their respective controls--in which one or both eyes were reversibly immobilised by threads sutured to the eyes. In the first condition the animals were rotated in the light with one eye immobilised and the other eye free to move but covered. Rotation in the light in this open-loop condition immediately elicited high-gain compensatory eye movements of the non-impeded, covered eye. At the end of this training procedure, the VOR gain increased by 43.2%. In the second condition, both eyes were immobilised and one eye was covered. The result was an increase in the VOR gain of 26.3%. These two conditions were similar as to the visuo vestibular drive during the exposure, but different as to the resulting--and allowed--eye motion, showing that the condition where the larger eye movements occurred yielded the larger VOR gain change. Our data support the idea proposed by Collewijn and Grootendorst (1979, p. 779) and Collewijn (1981, p. 146) that "[retinal] slip and eye movements seem to be relevant signals for the adaptation of the rabbit's visuo-vestibular oculomotor reflexes".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789446 TI - The colocalization of parvalbumin and calbindin-D28k with GABA in the subnucleus caudalis of the rat spinal trigeminal nucleus. AB - The colocalization of two calcium-binding proteins, parvalbumin (PV) and calbindin-D28k (CaB), which have been reported to be markers of specific subpopulations of neurons in the central nervous system, with the inhibitory amino acid neurotransmitter gamma-amino-butyric acid (GABA) was investigated in neurons of laminae I-IV of the subnucleus caudalis of the rat spinal trigeminal nucleus by using post-embedding immunocytochemical methods. Cells immunoreactive for PV, CaB, and GABA were found in all four laminae of the subnucleus caudalis. A substantial proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (44.8% and 39.8%, respectively). However, the majority of PV-containing neurons in laminae I and IV (100% and 86%, respectively), as well as CaB-immunoreactive cells in all four laminae (98.4%), were GABA-negative. These results show that, in contrast to higher brain centers, PV-, CaB-, and GABA immunoreactive perikarya represent significantly different populations of neurons in the subnucleus caudalis of the rat. In the light of the present findings, the differences in the neurochemical properties of the subnucleus caudalis of the spinal trigeminal nucleus and the spinal dorsal horn are also discussed. PMID- 7789448 TI - The curvature of human arm movements in the absence of visual experience. AB - It has been suggested that the spatial path of the hand is an important controlled feature of normal human arm movements and that the desired path is a straight line through external space. Recent experiments have suggested that distortions in visual perception of external space may lead to errors in its representation and thus influence the curvature of movements. The movements of blind and normal blind-folded subjects were therefore compared in a task requiring point-to-point hand movements in six directions across a horizontal worktop. Movement curvature varied with direction in both groups but was significantly higher for the blind-folded control subjects. Thus, the normals' distorted visual experience of straight lines in some orientations may lead them to make curved movement paths. The perception of curvature was also tested in the two groups in a task in which they traced the curved edge of a ruler. The blind group were slightly better at this task, although the difference was not significant. We conclude that visual experience influences point-to-point hand movements, leading to higher curvature for movements made in the fronto-parallel plane by sighted subjects due to visual distortions. These data therefore support the hypothesis that the spatial path followed by the hand is influenced by sensory inputs and is a controlled feature of human reaching movements. The data argue against the hypothesis that movement curvature is a result of optimising only the dynamics of the limb control. PMID- 7789447 TI - The responses of single neurons in the temporal visual cortical areas of the macaque when more than one stimulus is present in the receptive field. AB - Neurons in the temporal visual cortical areas of primates have large receptive fields, which can show considerable selectivity for what the stimulus is irrespective of exactly where it is in the visual field. This is called translation invariance. However, such results have been found when there is only one stimulus in the visual field. The question arises of how the visual system operates in a cluttered environment. To investigate this we measured the responses of neurons with face-selective responses in the cortex in the anterior part of the superior temporal sulcus of rhesus macaques performing a visual fixation task. We found that the response of neurons to an effective face centred 8.5 degrees from the fovea was decreased to 71% if an ineffective face stimulus for that cell was present at the fovea. In a similar way, introduction of a parafoveal ineffective face stimulus decreased the responses of these neurons to an effective face stimulus at the fovea to 75%. In addition to these interactions, it was found that an effective stimulus object at the fovea produced a larger response than when it was parafoveal, and that this weighting towards an object at the fovea was also seen when more than one object was present in the visual field. The implication of this weighting of the responses of neurons towards objects at the fovea, even in an environment with more than one object present, is that the output of the visual system provides information to subsequent systems particularly about objects at the fovea, so that learning about these objects (and less about other objects elsewhere in the visual field) is facilitated. PMID- 7789449 TI - Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection. AB - In two experiments movement-related cortical potentials preceding voluntary movement were recorded. In experiment 1, subjects performed four motor tasks involving joystick movements. The four tasks differed in complexity (single vs sequential movements) and in the mode of movement selection, i.e., whether a movement or movement sequence was made in fixed or in self-determined directions. The choice of these tasks was based, firstly, on previous electrophysiological studies suggesting an effect of task-complexity on the amplitude of the readiness potential (RP) and, secondly, on previous positron emission tomography (PET) studies showing that activity of the supplementary motor area (SMA) is influenced by the mode of movement selection. The results show that, for single movements, RP amplitude is higher preceding freely selected movements than preceding movements in a fixed direction. In experiment 2 this effect was replicated using button presses instead of joystick movements. The results converge with PET evidence obtained in similar tasks and establish that the RP is modulated by the mode of movement selection. This modulation is probably related to differential involvement of the SMA. PMID- 7789450 TI - The relationship between control, kinematic and electromyographic variables in fast single-joint movements in humans. AB - Two versions of the hypothesis that discrete movements are produced by shifts in the system's equilibrium point are considered. The first suggests that shifts are monotonic and end near the peak velocity of movement, and the second presumes that they are nonmonotonic ("N-shaped") and proceed until the end of movement. The first version, in contrast to the second, predicts that movement time may be significantly reduced by opposing loads without changes in the control pattern. The purpose of the present study was to test the two hypotheses about the duration and shape of the shift in the equilibrium point based on their respective predictions concerning the effects of perturbations on kinematic and EMG patterns in fast elbow flexor movements. Subjects performed unopposed flexions of about 55-70 degrees (control trials) and, in random test trials, movements were opposed by spring-like loads generated by a torque motor. Subjects had no visual feedback and were instructed not to correct arm deflections in case of perturbations. After the end of the movement, the load was removed leading to a secondary movement to the same final position as that in control trials (equifinality). When the load was varied, the static arm positions before unloading and associated joint torques (ranging from 0 to 80-90% of maximum voluntary contraction) had a monotonic relationship. Test movements opposed by a high load (80-90% of maximal voluntary contraction) ended near the peak velocity of control movements. Phasic and tonic electromyographic patterns were load dependent. In movements opposed by high loads, the first agonist burst was significantly prolonged and displayed a high level of tonic activity for as long as the load was maintained. In the same load conditions, the antagonist burst was suppressed during the dynamic and static phases of movement. The findings of suppression of the antagonist burst does not support the hypothesis of an N shaped control signal. Equally, the substantial reduction in movement time by the introduction of an opposing load cannot be reconciled in this model. Instead, our data indicate that the shifts in the equilibrium point underlying fast flexor movements are of short duration, ending near the peak velocity of unopposed movement. This suggests that kinematic and electromyographic patterns represent a long-lasting oscillatory response of the system to the short-duration monotonic control pattern, external forces and proprioceptive feedback. PMID- 7789451 TI - Influence of joint interactional effects on the coordination of planar two-joint arm movements. AB - We have examined EMG-movement relations in two-joint planar arm movements to determine the influence of interactional torques on movement coordination. Explicitly defined combinations of elbow movements (ranging from 20 to 70 degrees) and wrist movements (ranging from 20 to 40 degrees) were performed during a visual, step-tracking task in which subjects were specifically required to attend to the initial and final angles at each joint. In all conditions the wrist and elbow rotated in the same direction, that is, flexion-flexion or extension-extension. Elbow movement kinematics were only slightly influenced by motion about the wrist. In contrast, the trajectory of the wrist movement was significantly influenced by uncompensated reaction torques resulting from movement about the elbow joint. At any given wrist amplitude, wrist movement duration increased and peak velocity decreased as elbow amplitude increased. In addition, as elbow amplitude increased, wrist movement onset was progressively delayed relative to this elbow movement. Surprisingly, the changes between joint movement onsets were not accompanied by corresponding changes between agonist EMG onsets at the elbow and wrist joints. The mean difference in onset times between elbow and wrist agonists (22-30 ms) remained unchanged across conditions. In addition, a basic pattern of muscle activation that scaled with movement amplitude was observed at each joint. Phasic agonist activity at the wrist and elbow joints remained remarkably similar across conditions and thus the changes in joint movement onset could not be attributed to changes in the motor commands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789452 TI - Are arm trajectories planned in kinematic or dynamic coordinates? An adaptation study. AB - There are several invariant features of point-to-point human arm movements: trajectories tend to be straight, smooth, and have bell-shaped velocity profiles. One approach to accounting for these data is via optimization theory; a movement is specified implicitly as the optimum of a cost function, e.g., integrated jerk or torque change. Optimization models of trajectory planning, as well as models not phrased in the optimization framework, generally fall into two main groups those specified in kinematic coordinates and those specified in dynamic coordinates. To distinguish between these two possibilities we have studied the effects of artificial visual feedback on planar two-joint arm movements. During self-paced point-to-point arm movements the visual feedback of hand position was altered so as to increase the perceived curvature of the movement. The perturbation was zero at both ends of the movement and reached a maximum at the midpoint of the movement. Cost functions specified by hand coordinate kinematics predict adaptation to increased curvature so as to reduce the visual curvature, while dynamically specified cost functions predict no adaptation in the underlying trajectory planner, provided the final goal of the movement can still be achieved. We also studied the effects of reducing the perceived curvature in transverse movements, which are normally slightly curved. Adaptation should be seen in this condition only if the desired trajectory is both specified in kinematic coordinates and actually curved. Increasing the perceived curvature of normally straight sagittal movements led to significant (P < 0.001) corrective adaptation in the curvature of the actual hand movement; the hand movement became curved, thereby reducing the visually perceived curvature. Increasing the curvature of the normally curved transverse movements produced a significant (P < 0.01) corrective adaptation; the hand movement became straighter, thereby again reducing the visually perceived curvature. When the curvature of naturally curved transverse movements was reduced, there was no significant adaptation (P > 0.05). The results of the curvature-increasing study suggest that trajectories are planned in visually based kinematic coordinates. The results of the curvature reducing study suggest that the desired trajectory is straight in visual space. These results are incompatible with purely dynamic-based models such as the minimum torque change model. We suggest that spatial perception--as mediated by vision--plays a fundamental role in trajectory planning. PMID- 7789454 TI - Aftereffects from jogging. AB - After running on a treadmill, runners who attempted to jog in place on solid ground inadvertently jogged forwards. One-legged hopping on the treadmill produced an aftereffect in the same leg, but not in the other leg. This non transfer suggests a peripheral neural site. Judgments of velocity and slope were affected; running on a backward-moving treadmill made a stationary test treadmill seem to move forwards, and running on an uphill-sloping treadmill made a horizontal test treadmill seem to slope downhill. These aftereffects suggest an automatic gain control process. PMID- 7789453 TI - Compensation of the human vertical vestibulo-ocular reflex following occlusion of one vertical semicircular canal is incomplete. AB - The vestibulo-ocular reflex (VOR) was studied in nine human subjects 2-15 months after permanent surgical occlusion of one posterior semicircular canal. The stimuli used were rapid, passive, unpredictable, low-amplitude (10-20 degrees), high-acceleration (3000-4000 degrees/s2) head rotations in pitch and yaw planes. The responses measured were vertical and horizontal eye rotations, and the results were compared with those from 19 normal subjects. After unilateral occlusion of the posterior semicircular canal, the gain of the head-up pitch vertical VOR--the vertical VOR generated by excitation from only one and disfacilitation from two vertical semicircular canals--was reduced to 0.61 +/- 0.06 (normal 0.92 +/- 0.06) at a head velocity of 200 degrees/s. In contrast the gain of the head-down pitch vertical VOR--the VOR still generated by excitation from two, but disfacilitation from only one vertical semicircular canal--was within normal limits: 0.86 +/- 0.11 (normal 0.96 +/- 0.04). The gain of the horizontal VOR in response to yaw head rotations--ipsilesion 0.81 +/- 0.06 (normal 0.88 +/- 0.05) and contralesion 0.80 +/- 0.11 (normal 0.92 +/- 0.11)--was within normal limits in both directions (group means +/- two-tailed 95% confidence intervals given in each case). These results show that occlusion of just one vertical semicircular canal produces a permanent deficit of about 30% in the vertical VOR gain in response to rapid pitch head rotations in the excitatory direction of the occluded canal. This observation indicates that, in response to a stimulus in the higher dynamic range, compensation of the human VOR for the loss of excitatory input from even one vertical semicircular canal is incomplete. PMID- 7789455 TI - On the metabolism of apolipoprotein E and the Alzheimer diseases. PMID- 7789456 TI - Systemic administration of GM1 ganglioside increases choline acetyltransferase activity in the brain of aged rats. AB - In the brain of aged rats (22-24 months old) choline acetyltransferase (ChAT) activity in striatum and frontal cortex is lower than in young rats (4-5 months old). In contrast, ChAT activity in the hippocampus is similar in the two groups. Treating old animals with GM1 ganglioside, 30 mg/kg ip, for 30 or 45 days enhances ChAT activity in the striatum and frontal cortex, but has no effect on activity in the hippocampus. ChAT activity remains elevated in the striatum and frontal cortex for 15 days after discontinuing treatment with GM1. PMID- 7789458 TI - Plasticity of complex terminals in lamina II in partially deafferented spinal cord: the cat spared root preparation. AB - Projections to the dorsal horn change in adult mammals in response to complete or partial deafferentation. The number of synaptic terminals remains constant after complete lumbosacral deafferentation, indicating replacement of lost dorsal root terminals by newly formed terminals from spared intrinsic systems. The density of a spared central projection of a dorsal root is increased in dorsal horn after partial deafferentation, consistent with sprouting by the axons in the spared root. In this study, we have used electron microscopy to study morphological changes in a specific class of terminals in the dorsal horn induced by partial deafferentation. Complex terminals (CTs) in the dorsal horn originate exclusively from dorsal roots and are readily distinguished morphologically. The CTs and the postsynaptic densities (PSDs) associated with CTs were measured in lamina II at L5 and L6 in cats subjected to unilateral spared root (L6) dorsal rhizotomies and compared to CTs in the control side. Acutely following partial deafferentation, the number of CT profiles decreased. At more chronic survivals, the number of CT profiles were restored to normal levels, and both the number and the length of PSDs were increased. The changes in CTs and PSDs suggest sprouting and synaptogenesis by the spared dorsal root fibers that produce changes in the postsynaptic neuron. Spared root deafferentation thus elicits compensatory changes in presynaptic terminals of the spared root and also in their postsynaptic target neurons. PMID- 7789457 TI - Early association of reactive astrocytes with senile plaques in Alzheimer's disease. AB - The fibrillar beta-amyloid protein (A beta) plaques of Alzheimer's disease (AD) are associated with reactive astrocytes and dystrophic neurites and have been suggested to contribute to neurodegenerative events in the disease. We recently reported parallel in vitro and in situ findings, suggesting that the adoption of a reactive phenotype and the colocalization of astrocytes with plaques in AD may be mediated in large part by aggregated A beta. Thus, A beta-mediated effects on astrocytes may directly affect disease progression by modifying the degenerative plaque environment. Alternatively, plaque-associated reactive astrocytosis may primarily represent a glial response to the neural injury associated with plaques and not significantly contribute to AD pathology. To investigate the validity of these two positions, we examined the differential colocalization of reactive astrocytes and dystrophic neurites with plaques. Hippocampal sections from AD brains--ranging in neuropathology from mild to severe--were triple-labeled with antibodies recognizing A beta protein, reactive astrocytes, and dystrophic neurites. We observed not only plaques containing both or neither cell type, but also plaques containing (1) reactive astrocytes but not dystrophic neurites and (2) dystrophic neurites but not reactive astrocytes. The relative proportion of plaques colocalized with reactive astrocytes in the absence of dystrophic neurites is relatively high in mild AD but significantly decreases over the course of the disease, suggesting that plaque-associated astrocytosis may be an early and perhaps contributory event in AD pathology rather than merely a response to neuronal injury. These data underscore the potentially significant contributions of reactive astrocytosis in modifying the plaque environment in particular and disease progression in general. PMID- 7789460 TI - The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury. AB - Substantial residual neurological function may persist after spinal cord injury (SCI) with survival of as few as 5-10% of the original number of axons. A detailed understanding of the relationships among the severity of injury, the number and origin of surviving axons at the injury site, and the extent of neurological recovery after SCI is of importance in understanding the pathophysiology of SCI and in designing treatment strategies. In the present study, these relationships were examined in rats with graded severity of clip compression injury of the cord at T1. The rats were randomly assigned to one of the following injury groups (n = 5 each): normal (laminectomy only), 2-, 18-, 30 , 50-, and 98-g clip injuries. Neurological function was assessed by the inclined plane method and by the modified Tarlov technique. A morphometric assessment of axons at the injury site was performed by a computer-assisted line sampling technique. The origin of descending axons at the injury site was determined by retrograde labeling with horseradish peroxidase. The inclined plane scores varied as a negative linear function of the closing force of the clip used to inflict SCI (r = -0.93; P < 0.0001). The mean axon count was 367,000 +/- 59,000 in normal rats and decreased as a negative exponential function of injury force (r = -0.92; P < 0.0001). As well, SCI caused preferential destruction of large axons as reflected by the change in mean axon diameter from 1.74 +/- 0.06 microns in normal cords to 1.46 +/- 0.04 microns in injured cords (pooled mean for all injuries).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789459 TI - Transgenic neural plate contributes neuronal cells that survive greater than one year when transplanted into the adult mouse central nervous system. AB - Neural plate cells from the early embryo may have a number of important advantages as donor material for the delivery of foreign genes into the diseased adult central nervous system (CNS). Mesencephalic neural plate from transgenic GT4-2 mice was used as a source of marked donor cells to determine whether transgene-expressing embryonic CNS progenitor cells can be used as donor material for implantation into the adult mouse brain. Transgenic mouse embryos from this line express the Escherichia coli beta-galactosidase (beta-gal) gene throughout early CNS development. At the early somite stage (Embryonic Day 8.5), mesencephalic neural plate tissue from heterozygous embryos was dissected out and either transferred into culture for characterization or immediately implanted into the striatum or lateral ventricle of adult wild-type CD-1 mice. Explants of neural plate tissue possessed intense beta-gal activity and produced extensive outgrowth of neurofilament-positive processes after 6 days in vitro. Many beta gal-positive cells migrated away from the explanted tissue mass. Grafts of transgenic neural plate tissue in the normal adult mouse striatum, sampled 2 weeks to 1 year after implantation, possessed healthy beta-gal-positive cells. More detailed analysis of grafts 3 months after implantation indicated that most beta-gal-positive cells were also immunoreactive for neurofilament and microtubule-associated proteins, two neuron-specific markers. In addition, extensive neurofilament-positive axonal tangles were evident within the grafts among the beta-gal-positive cells. Electron microscopic (EM) findings of implanted tissue stained with Bluo-Gal revealed many beta-gal-positive neurons received synaptic contacts from other cells. A few donor-derived astrocytes were also found in the grafts by EM analysis. No obvious signs of immunological rejection, or of significant decrease in graft volume, were observed at any age. Some beta-gal-positive cells were observed to lie up to 230 microns away from the main graft mass in both striatal and intraventricular implantations. These data suggest that the neural plate can contribute a long-surviving population of neuronal and astrocytic cells when transplanted into the adult CNS. PMID- 7789461 TI - Regrowth of optic fibers and behavioral recovery after optic chiasm transection. AB - We studied the effect of optic chiasm midline transection on visually guided behavior and retinotectal fiber regrowth in frogs. After complete transection, frogs do not respond to visually presented prey and looming stimuli. Beginning about 2 months later there is recovery of visual function. However, unlike recovery after optic nerve transection, animals respond as if the stimulus were not at its actual position, but at the symmetric position in the contralateral field. For instance, if a prey stimulus is located 5 cm away from the recovered frog at an eccentricity of 40 degrees to the left of the midline, the animal will respond as if the stimulus were 5 cm away at 40 degrees right. Further, these animals typically respond to looming stimuli not by jumping away from the stimulus, but by either colliding with the stimulus or jumping toward the side from which the stimulus approaches. These behaviors persist throughout the testing period, up to 17.5 months postlesion. Electrophysiological recordings reveal that visual activity in the optic tectum is retinotopically organized but driven primarily by stimuli to the ipsilateral eye. HRP histochemistry reveals that some regenerated retinal fibers are found to cross at the midline of the chiasm. Thus, the midline is not impenetrable to crossing retinal fibers. Frogs with cut of 3/4 of the chiasm respond normally to prey stimuli initially but later respond as if the stimuli are at mirror image locations. In these animals most retinotectal fibers project to the ipsilateral tectum despite the presence of intact contralaterally projecting retinotectal fibers during the recovery period. PMID- 7789462 TI - Transganglionic degeneration in the gustatory system consequent to chorda tympani damage. AB - The chorda tympani taste nerve is prone to damage in humans. Chorda tympani damage results in taste loss accompanied by altered taste sensations, e.g., phantom tastes. To understand taste alterations this study explores the central and peripheral anatomical consequences of taste nerve injury in an animal model. The chorda tympani was severed in the middle ear of hamsters and the animals were allowed to survive for 2-161 days when sections of the brain were stained for degenerating axons with the Fink-Heimer method. Degenerating axons were present in the chorda tympani termination zone in the nucleus of the solitary tract of every case. Thus, peripheral nerve damage in the taste system results in degeneration of central axonal endings as in other sensory systems (e.g., trigeminal, vestibular). To evaluate whether the central degeneration results from ganglion cell death, geniculate ganglion cells were labeled with Fast blue by tongue injections before neurotomy, and the cells were counted 13-48 days after neurotomy. Numbers of labeled cells from experimental ganglia did not differ significantly from those in control ganglia. Moreover, the experimental cells could be double-labeled by tongue injections with a second marker, diamidino yellow or nuclear yellow, after 40 days postneurotomy. We conclude that degeneration of central axons after taste nerve section represents a long-lasting transganglionic process that likely disrupts the synaptology of the central taste system. The altered synaptology could relate to taste phenomena of central origin reported for nerve-injured patients. Geniculate ganglion cells generally survive neurotomy and can regenerate axons to the tongue. PMID- 7789463 TI - Peripheral target reinnervation following orthotopic grafting of fetal allogeneic and xenogeneic dorsal root ganglia. AB - The sensory reinnervation of dermal papillae and epidermis of glabrous skin, interosseal Pacinian corpuscles, and muscle spindles of the soleus and extensor digitorum longus muscles has been examined 1, 3, and 8 months (allografts) or 3 and 5 weeks (xenografts) following orthotopic grafting of fetal allogeneic or xenogeneic (mouse) dorsal root ganglia (DRG) into ganglionectomized adult rats. Sensory axons in target tissues were identified immunohistochemically by monoclonal antibodies against growth-associated peptide (GAP-43), heavy neurofilament protein (RT-97), anti-mouse-specific membrane glycoprotein Thy-1.2, and polyclonal antibody to calcitonin gene-related peptide (CGRP). Absence of axonal marker staining in target structures of control animals 10 days or 3 months following ipsilateral enucleation of the L3-L6 DRG without grafting indicated an elimination of host normal (intact), regenerating, or collaterally sprouting nerve fibers. The consistent finding of immunolabeled axons ending free and in encapsulated structures in the target tissues of both allo- and xenografted rats indicates that grafted primary sensory neurons can survive and send axonal processes down the full length of the hind limb, to terminate in host target tissues. Axons of xenografted fetal mouse sensory neurons grow in adult rat hosts for distances of 4 cm or more, attaining lengths far greater than called for by their normal developmental programs. PMID- 7789464 TI - Changes of compound action potentials in retrograde axonal degeneration of rat optic nerve. AB - Electrophysiological recordings of compound action potentials (CAPs) were made from the optic nerve (ON) following unilateral optic tract (OT) transection in adult rats. In response to optic chiasm stimulation CAPs recorded from the ON ipsilateral to the transected OT, i.e., the ON of control side, revealed three positive waves, termed n1, n2, and n3 components, corresponding to fast-, intermediate-, and slow-conducting fibers. Two weeks after OT transection, CAPs recorded from the ON contralateral to the transected OT, i.e., the ON of cut side, were generally smaller in amplitude than those recorded from the ON of control side. The degree of amplitude reduction was different among three components; n3 component was severely reduced and n2 component was moderately reduced, whereas n1 component relatively persisted. These tendencies were more marked in CAPs recorded at 4 weeks after OT transection; n3 component disappeared, whereas n1 and n2 components decreased in amplitude with elongation of latency. Cross sections of the ON after unilateral OT transection were examined electron microscopically, in which significant decrease in fiber density, demyelination, and distorted fibers were verified in the cut side. The present study suggests that slower-conducting ON fibers, that is, smaller diameter ON fibers are initially and remarkably thrown into retrograde degeneration, while larger-diameter ON fibers are relatively resistant to axotomy. PMID- 7789465 TI - Anticonvulsants suppress c-Fos protein expression in spinal cord neurons following noxious thermal stimulation. AB - The expression of the nuclear immediate-early gene-encoded protein c-Fos in spinal cord dorsal horn neurons of the rat following noxious thermal stimulation was compared in carbamazepine-, valproate- and phenytoine-treated animals. Single intraperitoneal injection of carbamazepine (50 mg/kg), valproate (300 mg/kg) or intravenous injection of phenytoine (20 mg/kg) before noxious stimulation reduced the number of c-Fos immunoreactive neurons to 65-80% of control levels in superficial laminae and to 30-60% in deep laminae of the dorsal horn. Pretreatment with carbamazepine or valproate for 4 or 8 days combined with an injection immediately before noxious stimulation further significantly decreased the number of c-Fos neurons in the deep dorsal horn only in animals treated with valproate. The observation that activity-dependent gene expression in the spinal cord is effectively modulated by anticonvulsants discloses a novel therapeutic potential of these compounds. Presumably via an acute suppression of high frequency repetitive firing and/or altered synaptic transmission of intraspinal or descending neurotransmitter systems these drugs gain access to neuroplastic mechanisms which might be relevant for the restoration of physiological levels of neuronal excitability in the central nervous system. PMID- 7789466 TI - Coenzyme Q10 and nicotinamide and a free radical spin trap protect against MPTP neurotoxicity. AB - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) produces Parkinsonism in both experimental animals and in man. MPTP is metabolized to 1-methyl-4 phenylpridinium, an inhibitor of mitochondrial complex I. MPTP administration produces ATP depletions in vivo, which may lead to secondary excitotoxicity and free radical generation. If this is the case then agents which improve mitochondrial function or free radical scavengers should attenuate MPTP neurotoxicity. In the present experiments three regimens of MPTP administration produced varying degrees of striatal dopamine depletion. A combination of coenzyme Q10 and nicotinamide protected against both mild and moderate depletion of dopamine. In the MPTP regimen which produced mild dopamine depletion nicotinamide or the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl) nitrone were also effective. There was no protection with a MPTP regimen which produced severe dopamine depletion. These results show that agents which improve mitochondrial energy production (coenzyme Q10 and nicotinamide) and free radical scavengers can attenuate mild to moderate MPTP neurotoxicity. PMID- 7789467 TI - Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. AB - Serum endotoxin, interleukin-6 (IL-6) and C-reactive protein (CRP) were serially determined in 26 patients with hematological malignancies and chemotherapy induced neutropenia who developed fever. Endotoxin in serum was detected in 69% of the patients, with the highest values being recorded in patients with gram negative (Gr-) bacteremia. High levels of IL-6 were found after start of fever, and in 6/9 patients with Gr- bacteremia levels exceeded 200 ng/l in samples drawn within the first 72 hours. However, only in 2/17 patients with gram-positive bacteremias and blood culture-negative fever episodes did IL-6 exceed this concentration (p < 0.05). High CRP values (exceeding 100 mg/l) did not discriminate between Gr- and non-Gr- episodes (7/9 versus 10/17, respectively). In patients with fever at day 3-5 (n = 15), IL-6 values > 100 ng/l were associated with fever continuing for more than 7 days after start of the episode; contrarily, CRP values did not indicate the persistence of fever. Determination of IL-6 may be a better test than CRP in monitoring the acute response to infection in the neutropenic patient. A combination of high endotoxin and IL-6 values may indicate a Gr- bacteremia. This could have therapeutic implications before results of blood cultures are obtained. PMID- 7789468 TI - Increased peripheral blood normal myeloid progenitor cells (CFU-GM) in chronic lymphocytic leukemia: a perspective for autologous peripheral blood stem cell transplantation. AB - We assayed granulocyte-macrophage committed progenitor cells (CFU-GM) in the peripheral blood of 34 patients with chronic lymphocytic leukemia (CLL) and 12 normal individuals. The patients were divided into separate groups on the basis of previous therapy (i.e. analysis performed at diagnosis, during and after chemotherapy) and clinical features of the disease (i.e. disease stage, pattern of bone marrow infiltration, peripheral blood lymphocytosis). The mean CFU-GM colony count of the patients was 30 times higher than that of the controls (206.4 +/- 197.8 (SD) CFU-GM per 5 x 10(5) cells plated versus 6.5 +/- 3.6). There was no statistical difference in the numbers of circulating CFU-GM between the patients studied at diagnosis (257 +/- 215.4 CFU-GM/5 x 10(5) cells) and those studied during (117.6 +/- 169.2 CFU-GM/5 x 10(5) cells) or after chemotherapy (207.5 +/- 105.9 CFU-GM/5 x 10(5) cells), although a trend towards a higher recovery of myeloid progenitors was observed as a function of time elapsing from the last treatment. In addition, we found no significant difference in the in vitro CFU-GM growth of patients grouped according to their disease stage, pattern of bone marrow infiltration and degree of peripheral blood lymphocytosis. In conclusion, our data indicate that intensification with peripheral blood stem cell support may be feasible in CLL, since progenitor cells of myeloid-monocytic series are markedly increased in the peripheral blood of these patients. Moreover, it is possible to extend this kind of therapy to patients who have undergone previous extensive chemotherapy and who might have persisting bone marrow infiltration. PMID- 7789469 TI - Refractory anemia with excess of blasts: a multivariate analysis of prognostic factors in 91 patients and a simplified scoring system for predicting survival. AB - Prognosis in myelodysplastic syndromes is extremely variable. The prognostic value of the FAB classification has been demonstrated in many studies. However, within the same FAB subtype, some patients may experience prolonged survival, whereas others die in a few weeks. This prognostic heterogeneity makes the therapy decision difficult. In an attempt to identify significant prognostic factors for survival in refractory anemia with excess of blasts (RAEB), clinical and hematological characteristics were analyzed in 91 patients. Multivariate regression analysis showed that bone marrow total blast cells percentages, sex and hemoglobin level were the characteristics significantly associated with survival. A scoring index based upon these three characteristics may be proposed and had a great prognostic value (p < 0.00001). It allows us to separate patients into three groups with low, intermediate and high score with a median survival of 239, 133 and 45 days for each group respectively. This scoring index may be useful in the design of therapy and analysis of future clinical trials. However, its predictive value needs to be confirmed in other series. PMID- 7789470 TI - The frequently low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities. AB - Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50 100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits. PMID- 7789471 TI - Separate clones in concomitant multiple myeloma and a second B-cell neoplasm demonstrated by molecular and immunophenotypic analysis. AB - The occurrence of multiple myeloma (MM) and a second B-cell neoplasm in the same patient is a rare event. We present 2 such patients, and provide evidence to support the presence of separate clones in these coexisting neoplasms. In the first case, MM became evident 14 months after the diagnosis of chronic lymphocytic leukemia (CLL). In past reports, most occurrences of this association, when investigated, have been regarded to be biclonal disease processes; however, with few exceptions, most were documented by immunologic studies alone. To establish the clonality in our case of CLL with MM, we examined both immunophenotypic data obtained by standard two-color flow cytometric analysis, and patterns of immunoglobulin gene rearrangement, using standard Southern analysis and hybridization with 32P-labelled JH and JK probes. This provided evidence for the presence in this patient of two separate monoclonal populations of B cells, manifested as light chain restrictions and gene rearrangements which differed in blood (CLL) and bone marrow (MM) samples. In the second case, MM presented simultaneously with bone marrow lymphocytosis and abnormal peripheral lymphocytes. Clonality studies on blood were not done. Bone marrow B-cell gene rearrangement studies, however, revealed the presence of three bands in the JK blot of significantly different intensities, suggestive of two monoclonal populations. A monoclonal population of small cells with surface B markers and surface IgM was demonstrated by flow cytometry, while a second population of larger cells with intracytoplasmic IgG matching the patient's serum monoclonal protein was detected by immunofluorescence microscopy. The results in these 2 cases expand previous findings of the rare association of MM with a second B-cell neoplasm, and demonstrate the usefulness of molecular diagnostic investigation. PMID- 7789472 TI - Chronic myelomonocytic leukemia preceding high-grade immunoblastic lymphoma. PMID- 7789473 TI - Erythrocyte glucose 6 phosphate dehydrogenase deficiency in east Andalusia (Spain) PMID- 7789474 TI - Omeprazole-associated agranulocytosis. PMID- 7789476 TI - Prospective study of risk factors for early and persistent wheezing in childhood. AB - The object of this study was to determine the relative importance of low birth weight, preterm birth, low maternal age, household size, exposure to maternal smoking, personal smoking at 16 yrs of age, early termination of breastfeeding and socioeconomic status in the aetiology of wheezing illness in the first 5 yrs of life, and on the persistence of this illness at 16 yrs of age. In 15,712 children born in Britain during one week of April 1970, the occurrence of wheezing by 5 yrs of age, and of wheezing in the past year at 16 yrs of age within this group were analysed in multivariate logistic regression against each potential risk factor. The independent determinants of wheezing by 5 yrs of age were male sex, maternal smoking during pregnancy (odds ratio (OR) for 15+ cigarettes.day-1 = 1.39; 95% confidence interval (95% CI) 1.22-1.58) and low birthweight (OR for birthweight < 2.5 kg = 1.26; 95% Cl 1.07-1.50). Of children who had wheezed by 5 yrs of age, 15% reported wheezing in the past 12 months at 16 yrs of age. The persistence of symptoms at 16 yrs of age was independently related to low maternal age (OR for 20 vs 40 yrs of age = 1.96; 95% CI 1.08-3.45) and to high social status (OR for most vs least advantaged = 1.95; 95% CI 1.13 3.38). We conclude that low birth weight and maternal smoking in pregnancy are independent risk factors for early childhood wheezing, but in 85% of children with early wheezing it resolves by 16 yrs of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789475 TI - Theophylline and phosphodiesterase inhibitors. PMID- 7789477 TI - Effect of altitude on urinary leukotriene (LT) E4 excretion and airway responsiveness to histamine in children with atopic asthma. AB - Asthmatic subjects who are resident at altitude may experience a deterioration in lung function following a stay at sea level. To determine whether measurement of urinary leukotriene E4 (LTE4) reflects changes in asthma severity and airway responsiveness, 14 allergic asthmatic subjects resident at altitude (1560 m, Davos, Switzerland) were studied. Subjects were randomly divided into two groups. Measurements of baseline forced expiratory volume in one second (FEV1), the concentration of histamine producing a 20% decrease in FEV1, (PC20 FEV1), serum total immunoglobulin E (IgE), eosinophil count, and urinary LTE4 concentration were determined prior to and following a 2 week stay in The Netherlands (sea level) in eight subjects (4 males and 4 females, aged 14 +/- 0.5 yrs) (mean +/- SEM) and over a similar time period in six subjects (4 males and 2 females, aged 15 +/- 0.3 yrs) resident in Davos, Switzerland. There was no significant difference in total IgE and eosinophil count, and no significant correlation between urinary LTE4 and PC20FEV1 histamine, FEV1, total IgE, and eosinophil count. In subjects returning to Davos from The Netherlands there was a significant increase in urinary LTE4 from a baseline value of 16.9 pg.mg-1 creatinine (GM, range 0.3-101.7 pg.mg-1 creatinine) to 52.3 pg.mg-1 creatinine (GM, range 8.8-301.6 pg.mg-1 creatinine), a significant decrease in PC20FEV1 from 1.7 mg.ml-1 (GM, range 0.3-16.4 mg.ml-1) to 0.9 mg.ml-1 (GM, range 0.1-->32 mg.ml 1), and a significant fall in FEV1 from 3.0 +/- 0.3 to 2.8 +/- 0.3 l (mean +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789478 TI - The measurement of methacholine responsiveness in 5 year old children: three methods compared. AB - The aim of this study was to compare the feasibility of three techniques for measuring the response to bronchial challenge in young children: a direct airway measurement, the forced oscillation technique (FOT) for determining respiratory system resistance at 6 and 8 Hz (Rrs6 and Rrs8), and two indirect methods, the change in transcutaneous oxygen tension (PtcO2) and the detection of wheeze on auscultation of the chest. Thirty children aged 5 yrs, with a history of wheeze, and six asymptomatic controls, took part in a bronchial challenge test using methacholine administered by Wright nebulizer by the tidal-breathing method. The provocative concentration which produced a 35% increase in Rrs6 (PC35Rrs6) and a 15% decreases in PtcO2 (PC15PtcO2) were determined by interpolation, and the chest was ausculated after each dose of methacholine. The FOT was found to be unreliable in this age group: in seven children, the data were technically unsatisfactory in the presence of induced bronchoconstriction, whilst in three children, changes in Rrs were inconsistent after challenge. The use of Rrs8 did not improve the detection of positive responses. PC15PtcO2 was measurable in 29 of 30 children, and in 18 of these PC35Rrs6 was also measurable. In no subject did a significant, sustained increase in Rrs occur during challenge in the absence of a significant change in PtcO2. Wheeze was audible in only 4 of 25 (16%) of the positive and in no negative challenges. With this protocol, we found the FOT to be unreliable and the auscultation method valueless and potentially dangerous, since marked falls in PtcO2 of up to 33% sometimes occurred in the absence of wheeze.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789479 TI - Variability of FVC and FEV1 due to technician, team, device and subject in an eight centre study: three quality control studies in SAPALDIA. Swiss Study on Air Pollution and Lung Disease in Adults. AB - Lung function testing of a random population sample in the eight SAPALDIA (Swiss study on air pollution and lung diseases in adults) centres had to be performed simultaneously, within one year, by eight teams and 23 technicians. We conducted quality control studies to test for technician, team and device related systematic measurement errors. To assess technician effects, each centre conducted a study involving 12-19 subjects. Two studies with 13 participants each addressed team and device effects. In all studies, volunteers repeatedly performed spirometry with different technicians or devices. Effects due to technician, team or device were estimated (analysis of variance). Neither "technician" within any of eight teams nor "team" accounted for significant differences of forced vital capacity (FVC) or forced expiratory volume in one second (FEV1). The Device Effect Study revealed 10% lower FVC values for device No. 1 due to a technical problem occurring during the test day but not in the main SAPALDIA study. Further investigations revealed potential hardware and software sources of error which are not recognizable by trained technicians. These studies gave no evidence for systematic errors due to technician, team or device during the main SAPALDIA study. However, they revealed potential sources of error in modern devices, which function as "black boxes". Manufacturers should improve spirometry software to further enhance the technicians' attempts at accurate assessment. PMID- 7789480 TI - Latent pulmonary function abnormalities in children with Crohn's disease. AB - Recently, latent pulmonary involvement has been described in adult patients with inflammatory bowel disease. It is unknown, however, whether this also occurs in children, and whether the pulmonary abnormalities differ between the acute phase and remission. The incidence of pulmonary abnormalities has been investigated in 26 children with acute or quiescent Crohn's disease in terms of the following parameters: clinical pulmonary symptoms, chest roentgenograms and pulmonary function tests, including lung transfer factor for carbon monoxide (TLCO). One child had a severe digital clubbing. Chest radiographs were normal in all subjects. No significant differences were found between acute and quiescent phase for pulmonary volumes and expiratory flows, but TLCO (% predicted) was significantly decreased during the active phase of the disease as compared to remission (53 +/- 15 vs 81 +/- 19% predicted). These data suggest that latent pulmonary involvement is also present in a paediatric population with active Crohn's disease, despite a short disease history and absence of smoking. Although the nature of this abnormality remains unclear, this extradigestive epiphenomenon should be taken into account with respect to the aetiopathogenesis of Crohn's disease. PMID- 7789481 TI - Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus. AB - Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml 1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789482 TI - Activation of the transcription factor NF-kappa B in human tracheobronchial epithelial cells by inflammatory stimuli. AB - Recent studies have shown that surface epithelial cells play a major role in the defence and inflammatory reactions of the airways. How extracellular stimuli lead to increased gene expression in these epithelial cells is not well known. In this study, we asked whether the multiunit transcription factor, nuclear factor (NF) kappa B, which regulates the expression of genes involved in defense and immune processes, is activated in airway epithelial cells following stimulation with inflammatory mediators and hydrogen peroxide. In addition, we studied whether this would be followed by upregulation of the NF-kappa B target gene product granulocyte-macrophage colony-stimulating factor (GM-CSF). Activation of NF-kappa B in the SV40 transformed human tracheobronchial epithelial cell line 1HAEo- was measured by electrophoretic mobility shift assays. GM-CSF concentrations in cell culture supernatants were determined by enzyme-linked immunosorbent assays. NF kappa B was rapidly activated by exposure of cells to interleukin-1 beta (IL-1 beta), phorbol myristate acetate (PMA), and tumour necrosis factor-alpha (TNF). Exposure to H2O2 platelet activating factor (PAF) and lipopolysaccharide (LPS) did not lead to increased NF-kappa B activation. Co-stimulation of IL-1 beta with H2O2 led to augmentation and prolongation of the effect on NF-kappa B activation compared to stimulation with IL-1 beta alone. GM-CSF concentrations increased following stimulation with IL-1 beta and H2O2, and the effect of IL-1 beta/H2O2 co-stimulation on GM-CSF concentrations was additive. These results suggest that NF-kappa B may represent an important transcription factor, controlling the expression of cytokine genes in airway epithelial cells. PMID- 7789483 TI - Prognostic analysis and predictive rule for outcome of hospital-treated community acquired pneumonia. AB - In community-acquired pneumonia (CAP) mortality may be reduced by early identification of patients requiring intensive care treatment. The purpose of this study was to determine prognostic factors of outcome in patients with CAP in order to establish a clinically applicable discriminant rule. Ninety three episodes of CAP in 92 patients were retrospectively reviewed with regard to epidemiological, clinical, laboratory and microbiological data. The prognostic analysis included a univariate as well as a multivariate approach, in order to identify parameters associated with death using the Cox regression hazard function in a backward stepwise selection model. The three parameters found to contribute most to the significance of the model were used in a discriminant rule for classification of outcome. The parameters found to be significantly different between survivors and non-survivors were heart rate, systolic and diastolic as well as mean blood pressures, leucocyte count, percentage of lymphocytes, and lactate dehydrogenase (LDH) values. The multivariate analysis revealed that heart rate, systolic arterial pressure, and LDH serum levels were most closely associated with fatal outcome. A prognostic rule composed of the variables heart rate > or = 90 beats.min-1, systolic arterial blood pressure < or = 80 mmHg, and LDH > or = 260 U.l-1 achieved a sensitivity of 77%, a specificity of 75%, and positive and negative predictive values of 42 and 93%, respectively. It was associated with a six fold increased risk of fatal outcome. In conclusion, heart rate, systolic blood pressure, and LDH values were most closely associated with death in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789484 TI - Efficacy of a three day course of azithromycin in moderately severe community acquired pneumonia. AB - This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789485 TI - Lung surfactant protein-A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma. AB - Lung surfactant protein-A (SP-A) is a major phospholipid-associated glycoprotein in surfactant, and is a useful immunohistochemical marker for lung adenocarcinoma. Carcinoembryonic antigen (CEA) has not been immunohistochemically detected in mesothelioma. In pleural effusions due to malignant mesothelioma, very low concentrations of SP-A and CEA can be expected. We studied the value of combined determinations of CEA and SP-A in pleural fluid to distinguish between lung adenocarcinoma and mesothelioma. SP-A and CEA concentrations were measured in pleural effusions from 78 patients with lung adenocarcinoma and 10 with malignant mesothelioma. SP-A concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 516 +/- 140 and 16.9 +/- 3.6 ng.ml-1 (mean +/- SEM), respectively. CEA concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 239 +/- 92.4 and 1.7 +/- 0.3 ng.ml-1, respectively. SP-A values did not exceed 100 ng.ml-1 in any of 10 mesotheliomas, whilst in 37 of 78 lung adenocarcinomas they did. CEA values did not exceed 10 ng.ml-1 in any of 10 mesotheliomas, whilst in 53 of 78 lung adenocarcinomas they did. Increased values of SP-A and/or CEA were found in pleural effusions from 67 of 78 lung adenocarcinomas. It is concluded that a combination of CEA and SP-A assays in pleural effusions will be helpful for discriminating lung adenocarcinoma from mesothelioma. PMID- 7789486 TI - Prostaglandin D2-induced bronchoconstriction is mediated only in part by the thromboxane prostanoid receptor. AB - Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, and is thought to have a role in the pathogenesis of asthma. PGD2 causes vasodilation acting via the prostaglandin (DP) receptor on vascular smooth muscle, and myocontraction acting via the thromboxane (TP) receptor on bronchial smooth muscle. To determine the relative contribution of these mechanisms we have studied the degree to which a potent TP receptor antagonist inhibits PGD2-induced bronchoconstriction. Twelve atopic asthmatic subjects underwent baseline PGD2 bronchial challenges to determine the cumulative concentration of PGD2 required to reduce forced expiratory volume in one second (FEV1) by 20%. At four subsequent randomized visits, subjects received this concentration of PGD2 90 min after dosing with placebo or 20, 50 or 100 mg of BAY u 3405, a potent competitive TP receptor antagonist. Serum was taken for drug assay at 90 min. After each dose of PGD2, FEV1 was measured for 30 min, and the area under the percentage fall in the FEV1/time curve (AUC) was calculated. The mean +/- SEM AUC for placebo was 414 +/ 68, and for the 20, 50 and 100 mg doses of BAY u 3405 was 169 +/- 33, 173 +/- 59 and 135 +/- 63, respectively. There were no significant differences between the AUCs for any of the drug doses, whilst all three doses were significantly different from placebo. The plateau response achieved with increasing doses of the antagonist suggests complete blockade of the TP receptor. These data demonstrate that thromboxane receptor blockade only partially inhibits the airway narrowing response to PGD2, and support the existence of a vascular component to PGD2-induced acute airway narrowing in asthma. PMID- 7789489 TI - Haemodynamic effects of nasal continuous positive airway pressure in severe congestive heart failure. AB - Nasal continuous positive airway pressure (NCPAP) during sleep may be a useful adjunct to medical therapy in patients with stable severe congestive heart failure (CHF), particularly when there is a coexisting respiratory sleep disorder. However, the direct haemodynamic effects of NCPAP in patients with severe stable CHF have not yet been adequately assessed. Right heart catheter studies were performed in seven awake males (aged 51-75 yrs) with stable CHF, before, during and after the application of 5 cmH2O NCPAP over 3 h. All patients had left ventricular ejection fractions < or = 30% and baseline pulmonary capillary wedge pressures > 12 mmHg, and six patients were in atrial fibrillation. Cardiac index fell from baseline in all patients whilst on NCPAP, with the greatest fall at 2 h (from 3.3 +/- 0.3 (mean +/- SEM) at baseline to 2.8 +/- 0.2 l.min-1.m-2) and rose back to baseline after NCPAP withdrawal. Systemic vascular resistance (SVR) increased during NCPAP application (1,268 +/- 108 to 1,560 +/- 82 dyn.s-1.cm5), with baseline SVR showing a significant negative correlation vs percentage fall in cardiac index (CI) at 2 h on multiple linear regression analysis (r2 = 0.8). These data indicate that domiciliary nocturnal NCPAP should not be prescribed as part of the therapy in severe CHF without first determining the individual patient's cardiac response to such therapy. PMID- 7789488 TI - Effect of protriptyline, 10 mg daily, on chronic hypoxaemia in chronic obstructive pulmonary disease. AB - A daily dose of 20 mg of protriptyline can improve daytime arterial blood gas tensions in chronic obstructive pulmonary disease (COPD). Its usefulness is limited by anticholinergic side-effects. This study examined whether a daily dose of 10 mg of protriptyline improved daytime arterial oxygen tension (PaO2) and quality of life in patients with stable mild or moderate hypoxaemia caused by COPD. Twenty six patients were randomized to receive protriptyline or placebo in a double-blind parallel-group trial for 12 weeks, following a run-in period of 4 weeks, in order to assess the stability of hypoxaemia. Patients with a change in PaO2 of > 0.7 kPa during the run-in were excluded. Spirometry, quality of life and dyspnoea score were measured at randomization and after 12 weeks, whilst arterial blood gas tensions were also measured 2 and 6 weeks after randomization. No improvement in arterial blood gas tensions, spirometry values, dyspnoea score, or quality of life was found in either the protriptyline or the placebo group. The majority of patients receiving protriptyline experienced anticholinergic side effects, which necessitated the withdrawal of the drug in one patient. We conclude that there was no evidence that a daily dose of 10 mg of protriptyline had a significant effect on daytime arterial oxygen tension in stable mild and moderate hypoxaemia caused by COPD. Despite the low dose, anticholinergic side effects occurred in most patients. PMID- 7789487 TI - The effect of 1 ppm nitrogen dioxide on bronchoalveolar lavage cells and inflammatory mediators in normal and asthmatic subjects. AB - Several studies have suggested that patients with bronchial asthma are more susceptible to the potential effects of nitrogen dioxide (NO2) than healthy subjects, with respect to airway responsiveness and lung function. We investigated whether these differences are paralleled by differences in the cellular and biochemical response within the airway lumen. Twelve subjects with mild extrinsic asthma and eight normal subjects breathed either filtered air or 1 ppm NO2 in a single-blind manner during intermittent exercise for 3 h. Bronchoscopy with bronchoalveolar lavage (BAL) was performed one hour after each exposure, and on a third day without exposure (baseline day). Prostanoids, leukotrienes and histamine were analysed in BAL fluid, and the cellular composition of BAL fluid was assessed. In the asthmatic subjects, NO2 induced a small mean drop in forced expiratory volume in one second (FEV1). Differential cell counts in BAL fluid did not reveal significant effects of NO2. Levels of 6 keto-prostaglandin1 alpha (6-keto-PGF1 alpha) were decreased, and levels of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2) in BAL fluid were increased after NO2 compared to filtered air exposure; whereas, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), histamine and leukotriene levels did not change significantly. The normal subjects showed no change in lung function parameters and a small increase in TxB2 after breathing NO2. We conclude that in subjects with mild asthma NO2 is capable of inducing an activation of cells, which is compatible with enhancement of airway inflammation, even if lung function parameters and cellular composition of BAL fluid are not markedly affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789490 TI - Nocturnal assisted ventilation using bilevel positive airway pressure: the effect of expiratory positive airway pressure. AB - Increasing expiratory positive airway pressure (EPAP) has theoretical advantages during overnight nasal ventilation. We wanted to evaluate the effect of the addition of EPAP upon the control of nocturnal hypoventilation. Seven patients with neuromuscular/skeletal (NMS) disorder (mean +/- SD forced vital capacity (FVC) 1.06 +/- 0.28 l, arterial oxygen tension (PaO2) 9.1 +/- 0.6 kPa, and arterial carbon dioxide tension (PaCO2) 6.9 +/- 0.9 kPa), and seven patients with chronic obstructive pulmonary disease (COPD) (FEV1 0.46 +/- 0.14 l, PaO2 6.2 +/- 0.6 kPa, and PaCO2 8.4 +/- 1.1 kPa) all underwent full polysomnography on two nights during bilevel positive airway pressure (BiPAP) ventilation, with and without the addition of expiratory positive airway pressure, which was matched to the level of dynamic positive end-expiratory pressure (PEEP) or set at a minimum value of 5 cmH2O. In the group with neuromuscular/skeletal disorders the maximum transcutaneous carbon dioxide tension (PtcCO2) overnight was lower (inspiratory positive airway pressure (IPAP) 8.1 +/- 1.4 kPa, IPAP/EPAP 7.3 +/- 0.9 kPa) and the minimum level of arterial oxygen saturation (SaO2 min) increased (IPAP 77.1 +/- 6.7%, IPAP/EPAP 83.6 +/- 4.2%) when expiratory positive airway pressure was added. There were no differences in mean PtcCO2 or mean oxygen saturation, but sleep quality was worse (non-rapid eye movement (non-REM) sleep IPAP 266 +/- 44 min, IPAP/EPAP 226 +/- 32 min). In the patients with COPD, expiratory positive airway pressure conferred no advantage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789492 TI - Lung elastic recoil in normal young adult Chinese compared with Caucasians. AB - Chinese people have smaller total lung capacity (TLC) compared with Caucasians of similar age, sex and height. One possible reason would be a higher lung elastic recoil in Chinese. Most published values for lung elastic recoil viz static lung compliance (CLst), shape constant K, and maximal static transpulmonary pressure (PLmax) have been from Caucasian subjects. The aim of our study was to obtain values for lung elastic recoil in normal young adult Chinese subjects. Static expiratory pressure-volume (P-V) curves were studied in 22 healthy Chinese subjects (12 males and 10 females). The P-V curve was fitted using an iterative least mean squares regression on a computer, according to an exponential equation: V = A-Be-KP, where V is lung volume, P is transpulmonary pressure, and A, B and K are constants. Mean values +/- SD for K, CLst and PLmax were 0.12 +/- 0.04, 230 +/- 103 ml.cmH2O-1 and 27.5 +/- 7.5 cmH2O, respectively. The values of CLst and K were similar to that of normal Caucasian subjects, whereas values of PLmax were lower. We attributed the lower PLmax partly to weaker inspiratory muscles in Chinese compared with Caucasians. We conclude that lung elastic recoil in normal young adult Chinese is similar to that of healthy young adult Caucasians. Hence, lung elasticity is unlikely to explain the racial differences in static lung volumes. PMID- 7789491 TI - Activity of latissimus dorsi muscle during inspiratory threshold loads. AB - The ability of the latissimus dorsi muscle (LD) to participate as an accessory inspiratory muscle has been the subject of controversy. Electromyographic (EGM) activity of LD was evaluated in 11 healthy subjects (aged 30 +/- 2 yrs; forced expiratory volume in one second (FEV1) 106 +/- 5% predicted; maximal inspiratory pressure (Pmax), 120 +/- 6 cmH2O) under different breathing conditions. The ipsilateral biceps brachii was chosen as the control muscle. The EMG was recorded from surface electrodes, but needle electrodes were also used for LD evaluation in a subset of three subjects. The EMG signal from both muscles was recorded simultaneously, rectified and integrated, with subtraction of the electrocardiographic signal. Situations evaluated were: 1) maximal voluntary contraction (MVC); 2) apnoea; and 3) breathing under progressive inspiratory threshold loads (20-100% Pmax, at 20% intervals). A close relationship was evident between LD recordings from surface and needle electrodes (r = 0.975). Activity of LD at baseline was 1.8 +/- 0.4% MVC, and showed a phasic increase during inspiration under loads. This change had a linear tendency and was significant for loads corresponding to 40, 60, 80 and 100% of Pmax when compared to the control muscle. At this latter level, LD activity was equivalent to 32 +/- 5% MVC (range 11-61%), whereas mean activity of the control muscle was less than 7.5% MVC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789493 TI - Biochemical characteristics of lungs in senescence-accelerated mouse (SAM). AB - This study examined age-related biochemical changes of the lung in an animal model of senile lung, senescence-accelerated mouse (SAM). Bronchoalveolar lavage (BAL) was performed on two strains of SAM, the senescence-prone strain (SAM P2) and the senescence-resistant strain (SAM R1), as well as on normal ageing C57 black mice (C57BL), aged 1-24 months. Elastase-like and elastase inhibitory activity of BAL fluid (BALF), glutathione (GSH) and oxidized GSH (GSSG) content both of BALF and lung tissue, and oxygen radical generation of free lung cells obtained by BAL were examined in the three strains of mice. Cell populations did not change throughout the life in SAM strains and C57BL. The elastolytic activity in SAM was greater than in C57BL, but there was no change with age. Both a decreased content of GSH and an increased oxidation of the GSH in BALF were markedly observed with ageing in SAM P2. In the lung tissue, the GSSG/GSH ratio in SAM strains was consistently greater than that in C57BL, suggesting that the GSH redox cycle of the lung may be impaired in SAM strains. The oxygen radical generation by free lung cells increased with age in all three strains, but the increase was earlier and more pronounced in SAM P2 than in the other two strains. In conclusion, an impaired GSH redox cycle and an increased formation of oxygen radicals are observed in the lungs of SAM with increasing age. PMID- 7789495 TI - A threshold loading device for testing of inspiratory muscle performance. AB - Threshold loading is a method of incrementally loading the inspiratory muscles, which requires development of an adjustable threshold pressure (Pth) before air will flow. In the ideal device, flow is independent of pressure once Pth is exceeded. A "weighted plunger" apparatus is commonly used, but devices described previously perform unreliably at high inspiratory load. We have modified this apparatus using the diaphragm and valve seating from a threshold valve used to deliver positive airway pressure (AMBU 10, AMBU International, Denmark) to yield improved pressure-flow characteristics. With this device, there was a linear relationship between Pth and weight on the plunger (r = 0.998), and flow was largely independent of pressure once Pth was exceeded: pressure developed at an inspiratory flow of 1.3 +/- 0.1 l.s-1 was 13.6 +/- 7.0% below Pth. Our modified weighted plunger apparatus allows consistent and reliable threshold loading of inspiratory muscles, even at high inspiratory loads. PMID- 7789494 TI - Cyclic nucleotides and phosphodiesterases and airway function. AB - The cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) play an important role in the regulation of airway smooth muscle tone and activation of inflammatory cells. Intracellular concentrations of these nucleotides are tightly regulated by phosphodiesterases (PDEs). Several families of PDEs are now recognized and, within each isoenzyme family, molecular cloning has revealed multiple members. PDE III and IV are important in the breakdown of cAMP; PDE III is involved in the regulation of airway smooth muscle tone, whereas PDE IV is more important in inflammatory cells, including mast cells, macrophages, eosinophils, T-lymphocytes and epithelial cells. PDE V is involved in the breakdown of cGMP in airway and vascular smooth muscle. Regulation of PDE expression in health and disease is now under investigation. Several selective PDE inhibitors have recently been developed, and experimental studies indicate that PDE IV inhibitors may be useful as anti-inflammatory treatments in asthma. Clinical trials in asthma are now in progress. PMID- 7789496 TI - Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker. AB - A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma. He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics. Symptoms disappeared after being transferred to the packaging section. When the subject was admitted to our department he was asymptomatic. Basal lung function tests were in the normal range. Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative. Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration. Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash. A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative. We conclude that piperacillin sodium is an agent that can cause occupational asthma. PMID- 7789497 TI - Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: a rare aetiology. AB - Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological entity with well-defined diagnostic criteria, the aetiology of which is generally unknown. Among the adverse pulmonary effects of the drug amiodarone, BOOP is the least commonly reported in the literature. In this article we describe a case of amiodarone-induced BOOP. PMID- 7789498 TI - Association of histologically proven rheumatoid arthritis with pulmonary sarcoidosis. AB - The association of rheumatoid arthritis proven by means of synovial biopsy with pulmonary sarcoidosis proven by means of bronchial biopsy, occurred in a 58 year old woman. Corticosteroid therapy resulted in complete resolution of sarcoidosis but only slight improvement of the rheumatoid arthritis, which was secondarily treated with methotrexate with a successful outcome. Only two similar cases have been reported with simultaneous histological proofs of both diseases. PMID- 7789500 TI - Three cases of bronchial stump aspergillosis: unusual clinical presentations and beneficial effect of oral itraconazole. AB - Bronchial stump aspergillosis (BSA), i.e. Aspergillus infection of bronchial granulation tissue surrounding endobronchial suture threads, is a very rare variant of localized suppurative bronchial Aspergillus infection. The majority of reported cases have occurred within one year after lung surgery. We present three more patients, in whom BSA occurred very late (4.5, 6 and 7 yrs) after pulmonary resection. Other unusual features were: complete absence of symptoms in one patient, and simultaneous occurrence of aspergilloma in another. Removal of the endobronchial suture probably constitutes the key therapy for BSA. In all three of our patients oral itraconazole resulted in clinical, histological and microbiological improvement. In conclusion, BSA should be considered in the differential diagnosis of haemoptysis occurring up to 7 yrs after lung surgery, although an asymptomatic presentation is possible. Furthermore, BSA can be associated with other clinical presentations of Aspergillus infection, e.g. aspergilloma. Finally, long-term oral itraconazole therapy may represent a valid alternative when removal of the suture is not feasible. PMID- 7789499 TI - Systemic sarcoidosis initially presenting as an orbital tumour. AB - A 73 year old woman presented with redness, itching and painless proptosis of the left eye. Clinical examination and computed tomographic (CT) scan of the orbit revealed a postero-ocular mass, the biopsy of which showed a noncaseating, giant cellular, epithelioid granuloma compatible with sarcoidosis. The patient had no respiratory complaints, but the thoracic CT scan showed multiple bilateral hilar and mediastinal adenopathies. Gallium scan showed increased uptake in both hilar regions, in the left orbit and in the right parotid gland. Multiple bronchial biopsies revealed sarcoid granulomas, with a bronchoalveolar lavage (BAL) cytological pattern of active sarcoidosis. The evolution was favourable with prednisolone given at a dose of 0.5 mg.kg-1 daily. It is suggested that in an unusual presentation of sarcoidosis, a thorough search should be made for localization at other sites, lungs in particular, even in the absence of respiratory complaints. PMID- 7789501 TI - Haemoptysis and a cavity in a young man. PMID- 7789502 TI - International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. AB - The aetiology of asthma and allergic disease remains poorly understood, despite considerable research. The International Study of Asthma and Allergies in Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease, by establishing a standardized methodology and facilitating international collaboration. Its specific aims are: 1) to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres, and to make comparisons within and between countries; 2) to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and 3) to provide a framework for further aetiological research into genetic, lifestyle, environmental, and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase 1 uses core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations. Phase 2 will investigate possible aetiological factors, particularly those suggested by the findings of Phase 1. Phase 3 will be a repetition of Phase 1 to assess trends in prevalence. PMID- 7789504 TI - Relationship of dietary fish intake to level of pulmonary function. PMID- 7789503 TI - Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of The European Respiratory Society. PMID- 7789505 TI - Structural analysis and comparison of the C-terminal transport signal domains of hemolysin A and leukotoxin A. AB - NMR spectroscopy was used to study the structure of the C-terminal signal sequences of the bacterial toxins, hemolysin A(HlyA) and leukotoxin A (LktA). The two signals share little sequence homology; however, both can direct toxin transport with equal efficiency. We report here that in a membrane mimetic environment both peptides form two short non-interacting alpha-helices separated by a short loop. This higher order structure may be a common feature of C terminal signals and may be required for interaction with the membrane associated transporter complex. PMID- 7789506 TI - Lysophosphatidic acid-induced activation of protein Ser/Thr kinases in cultured rat 3Y1 fibroblasts. Possible involvement in rho p21-mediated signalling. AB - Renaturation kinase assay was used to detect protein kinases activated by lysophosphatidic acid (LPA) in cultured rat 3Y1 fibroblasts. LPA activated several Ser/Thr protein kinases with apparent molecular weights of 145K, 85K, 64 65K (a doublet), and 60K (each named p145, p85, p64165 and p60, respectively) in addition to p43 mitogen activated protein (MAP)-kinase. Experiments using pertussis toxin and botulinum C3 exoenzyme showed that p145, p85, and p64165 kinases were activated by a pertussis toxin-insensitive rho p21-dependent pathway and that the activation of MAP-kinase was mediated by both the pertussis toxin sensitive rho p21-independent and the pertussis toxin-insensitive rho p21 dependent pathways. PMID- 7789507 TI - On the distribution of ligands within the asymmetric chaperonin complex, GroEL14.ADP7.GroES7. AB - In the presence of MgATP or MgADP the E. coli chaperonin proteins, GroEL and GroES, form a stable asymmetric complex with a stoichiometry of two GroEL7:one GroES7: seven MgADP. The distribution of the ligands between the two heptameric GroEL rings is crucial to our understanding of the mechanism of chaperonin assisted folding, being either cis (i.e. [GroEL7.MgADP7.GroES7]-[GroEL7]) or trans (i.e. [GroEL7.MgADP7]-[GroEL7.GroES7]. On the basis of cross-linking experiments with 8-azido-ATP and the heterobifunctional reagent, N-succinimidyl 3 (2-pyridyldithio) propionate (SPDP), it was suggested that GroES and MgADP are bound to the same GroEL ring which resists proteinase K digestion [Nature 366 (1993) 228-233]. However, we find that the SPDP-promoted cross linking of GroES and GroEL occurs in the absence of Mg2+, ADP or ATP, which are required for the formation of the asymmetric complex. Cross-linking is shown to occur only when the SPDP-modified GroES is co-precipitated with GroEL by trichloracetic acid. Furthermore, there are structural grounds for questioning whether SPDP can crosslink, in a physiologically relevant manner, an amino group of GroES with any of the cysteinyl groups of GroEL. PMID- 7789508 TI - Properties of omega conotoxin MVIIC receptors associated with alpha 1A calcium channel subunits in rat brain. AB - Solubilized 125I-omega conotoxin MVIIC receptors from rat cerebellum were immunoprecipitated by antibodies directed against the calcium channel alpha 1A subunit. Anti-alpha 1A antibodies recognized a 240-220, 180 and 160 kDa proteins in immunoblots of cerebellar membranes. Disuccinimidyl suberate cross-linked 125I omega conotoxin MVIIC to an alpha 2 delta-like 200-180 kDa subunit, which migrated at 150-140 kDa after disulfide reduction. These observations are consistent with a heteromeric structure in which high affinity omega conotoxin MVIIC binding sites formed by alpha 1A subunits are located in close proximity to peripheral alpha 2 subunits. PMID- 7789509 TI - Receptor of trans-zeatin involved in transcription activation by cytokinin. AB - Zeatin-binding protein (67 +/- 2 kDa) was isolated from the cytosol of the first leaf of 10-day-old barley plants. The protein fits to all requirements for a zeatin receptor: (i) it binds [3H]trans-zeatin reversibly and specifically, (ii) it is recognized by anti-idiotype antibodies from antiserum raised against trans zeatin, (iii) in concert with 10(-8) M trans-zeatin it activates rRNA synthesis in vitro in a transcription elongation system containing chromatin from barley leaves associated with RNA-polymerase I. In the presence of trans-zeatin, the protein activates also RNA synthesis directed by RNA-polymerase I and RNA polymerase II in isolated nuclei from barley leaves. PMID- 7789510 TI - ATP synthesis catalyzed by the mitochondrial F1-F0 ATP synthase is not a reversal of its ATPase activity. AB - The ADP(Mg2+)-deactivated oligomycin-sensitive F1-F0 ATPase of coupled submitochondrial particles treated with the substoichiometric amount of oligomycin was studied to test whether ATP synthesis and hydrolysis proceed in either direction through the same intermediates. The initial rates of ATP hydrolysis, oxidative phosphorylation, ATP-dependent, succinate-supported NAD+ reduction, and ATP-induced delta microH+ generation were measured using deactivated ATPase trapped by azide [Biochem. J. (1982) 202, 15-23]. Three ATP consuming reactions were strongly inhibited when azide was present in the assay mixtures, whereas ATP synthesis was not altered by azide. The unidirectional effect of azide is not consistent with three alternating binding sites mechanism operating in ATP synthesis and support our hypothesis on the existence of nucleotide(Mg2+)-controlled 'synthase' and 'hydrolase' states of the mitochondrial F1-F0 ATPase. PMID- 7789511 TI - The third nucleotide of the Gly coding triplet remembers the periodicity of the collagen chain. AB - Collagen is a fibrous protein with a primary structure with complex periodical features. We show using symbolic Fourier transform of the collagen cDNA sequence that basic periodical patterns appear there also. Strikingly they are present in the third position of triplets encoding Gly, which occupies each third position in the sequence of the protein, and to which selection on the protein level does not applied. Thus, the gene of collagen seems to appear due to pra-gene multiplication. PMID- 7789513 TI - Human prothymosin alpha inhibits division of yeast Saccharomyces cerevisiae cells, while its mutant lacking nuclear localization signal does not. AB - Effect of human prothymosin alpha and its mutant over-produced in S. cerevisiae on yeast cell division was studied. Wild-type prothymosin alpha appeared to block division of yeast cells. Its inhibitory action could be abolished by deletion of the last nine carboxy-terminal amino acids of prothymosin alpha containing nuclear localization signal, thus pointing to the nucleus as a compartment, where prothymosin alpha performs its action. PMID- 7789512 TI - Primary structures of two homologous subunits of PA28, a gamma-interferon inducible protein activator of the 20S proteasome. AB - The primary structures of two proteins that comprise PA28, an activator of the 20S proteasome, have been determined by cDNA cloning and sequencing. These protein subunits, termed PA28 alpha and PA28 beta, are about 50% identical to one another and are highly conserved between rat and human. PA28 alpha and PA28 beta are homologous to a previously described protein, Ki antigen, whose function is unknown. PA28 alpha, but neither PA28 beta nor Ki antigen, contains a 'KEKE motif', which has been postulated to promote the binding of proteins having this structural feature. PA28 alpha and PA28 beta were coordinately regulated by gamma interferon, which greatly induced mRNA levels of both proteins in cultured cells. The mRNA level of the Ki antigen also increased in response to gamma-interferon treatment, but the magnitude of the increase was less than that for the PA28s, and the effect was transient. These results demonstrate the existence of a new protein family, at least two of whose members are involved in proteasome activation. They also provide the basis for future structure/function studies of PA28 subunits and the determination of their relative physiological roles in the regulation of proteasome activity. PMID- 7789514 TI - The nucleotide sequence of the bacteriophage T5 ltf gene. AB - The nucleotide sequence of the bacteriophage T5 Bg/II-BamHI fragment (4,835 bp in length) known to carry a gene encoding the LTF protein which forms the phage L shaped tail fibers was determined. It was shown to contain an open reading frame for 1,396 amino acid residues that corresponds to a protein of 147.8 kDa. The coding region of ltf gene is preceded by a typical Shine-Dalgarno sequence. Downstream from the ltf gene there is a strong transcription terminator. Data bank analysis of the LTF protein sequence reveals 55.1% identity to the hypothetical protein ORF 401 of bacteriophage lambda in a segment of 118 amino acids overlap. PMID- 7789515 TI - Preliminary microwave irradiation of water solutions changes their channel modifying activity. AB - Earlier we have shown that millimetre microwaves (42.25 GHz) of non-thermal power, upon direct admittance into an experiment bath, greatly influence activation characteristics of single Ca(2+)-dependent K+ channels (in particular, the channel open state probability, Po). Here we present new data showing that similar changes in Po arise due to the substitution of a control bath solution for a preliminary microwave irradiated one of the same composition (100 mmol/l KCl with Ca2+ added), with irradiation time being 20-30 min. Therefore, due to the exposure to the field the solution acquires some new properties that are important for the channel activity. The irradiation terminated, the solution retains a new state for at least 10-20 min (solution memory). The data suggest that the effects of the field on the channels are mediated, at least partially, by changes in the solution properties. PMID- 7789516 TI - Arachidonic acid binds to apolipoprotein D: implications for the protein's function. AB - The lipocalin apolipoprotein D (ApoD) is associated in human plasma with lecithin cholesterol acyl transferase. It has also been found in high concentration in the fluid of gross cystic disease of the mammary gland. Using protein fluorescence quenching, it is shown that ApoD binds arachidonic acid (Ka of 1.6 x 10(8) M-1) and as previously known progesterone (Ka of 2.5 x 10(6) M-1), but neither cholesterol nor any of the other prostanoid molecules examined had measurable affinity. This specific binding of arachidonate, also observable directly, suggests a role for ApoD in the mobilisation of arachidonic acid, and hence prostaglandin synthesis. PMID- 7789517 TI - Human influenza virus recognition of sialyloligosaccharides. AB - Sialic acids are essential components of cell-surface receptors utilized by influenza viruses. To evaluate the recognition of asialic sugar parts of the receptor, three representative strains of human influenza A and B viruses were tested for their binding of a panel of sialyloligosaccharides. The highest affinity binding carbohydrate determinants recognized by the viruses in a context of different core structures were Neu5Ac alpha 2-3Gal for the type B virus, Neu5Ac alpha 2-6 Gal for the H3 subtype virus, and Neu5Ac alpha 2-6Gal beta 1 4GlcNAc for the H1 subtype virus. Penultimate to these determinants parts of the sialyloligosaccharides studied either contributed less significantly to the binding affinity, or interfered with the binding. PMID- 7789518 TI - Interaction of urea with an unfolded protein. The DNA-binding domain of the 434 repressor. AB - Experimental techniques are presented for the observation of the solvation of the unfolded form of a globular protein, the N-terminal 63-residue polypeptide from the 434 repressor, in 7 M aqueous urea solution by both water and urea. With the use of 15N-labelled urea it is demonstrated that the cross sections through two dimensional nuclear Overhauser enhancement (NOE) spectra at the chemical shifts of H2O and urea both contain direct NOEs with the protein, under conditions where exchange peaks are observed only in the water cross section. A preliminary analysis of the data showed that the residence times of urea molecules in solvation sites near the methyl groups of Val, Leu and Ile are significantly longer than those of water molecules in the same sites. PMID- 7789519 TI - Human glucose-6-phosphate dehydrogenase. Lysine 205 is dispensable for substrate binding but essential for catalysis. AB - By site-directed mutagenesis of the cloned human glucose-6-phosphate dehydrogenase cDNA, lysine 205 (the residue that after reacting with pyridoxal-5' phosphate renders inactive enzyme) was mutated to threonine (K205T) to remove the amino group, or to arginine (K205R) to displace the position of the amino group, in order to analyze the role of its nucleophilic group in position epsilon. Compared to the wild-type enzyme, the K205T and K205R mutants retain a specific activity of 2.6 and 11.4%, respectively; their catalytic specificity (Kcat/Km) is drastically decreased, whereas the Km values for both substrates are only slightly increased. These findings in the light of the 3D structure of G6PD suggest that the epsilon-amino group of lysine 205 can favour a hydrogen bond within the active pocket essential for catalysis. PMID- 7789520 TI - Co-operative regulation of endocytosis by three Rab5 isoforms. AB - Rab proteins are small GTPases involved in the regulation of membrane traffic. Rab5a has been shown to regulate transport in the early endocytic pathway. Here we report the isolation of cDNA clones encoding two highly related isoforms, Rab5b and Rab5c. The two proteins share with Rab5a all the structural features required for regulation of endocytosis. Rab5b and Rab5c colocalize with the both transferrin receptor and Rab5a, stimulate the homotypic fusion between early endosomes in vitro and increase the rate of endocytosis when overexpressed in vivo. These data demonstrate that three Rab5 isoforms cooperate in the regulation of endocytosis in eukaryotic cells. PMID- 7789522 TI - Structural requirements for oxidation of low-density lipoprotein by thiols. AB - Oxidation of low-density lipoprotein (LDL) by macrophages, endothelial cells and smooth muscle cells, may be mediated by production of free thiols in the presence of transition metals. We examined the structural requirements, within a series of cysteinyl derivatives, for oxidation of thiols and of LDL in Hams F10 medium. The primary mechanism by which such thiols mediate oxidation of LDL is largely independent of superoxide production, but strongly correlated with the susceptibility of each thiol to iron-catalysed auto-oxidation. These effects are compared and contrasted with thiol-dependent oxidation of LDL by stimulated human monocytes and macrophages. PMID- 7789523 TI - Analysis of the core components of Alzheimer paired helical filaments. A gas chromatography/mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases. AB - We have carried out a fatty acid and carbohydrate compositional analysis of the protease-resistant core of paired helical filaments (prcPHF) isolated from six Alzheimer's diseased brains. Fatty acids, long-chain bases and monosaccharides were characterized by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl esters, trimethylsilylated long-chain bases, peracetylated alditol acetates and trimethylsilyl methyl glycosides. Glucose and mannose were found to be the only carbohydrate components. Four of the six prcPHF samples contained only glucose while the remaining two samples contained between 30-40% mannose in addition to glucose. None of the samples were found to contain either hydroxylated fatty acids or long-chain bases. The average fatty acid profile of prcPHF was highest in stearic (C18:0) and palmitic acids (C16:0) with less than 10% unsaturated fatty acids. By comparing the carbohydrate and lipid composition of prcPHF to similar data for other brain glycolipids, it was determined that prcPHF is a unique glycolipid, distinct from cerebrosides, gangliosides or brain phospholipids. The fatty acid and carbohydrate composition of a glycolipid isolated from a population of normal brains according to the prcPHF protocol was found to be identical to that of prcPHF glycolipid. It is possible that subtle differences in structure or indigenous factors are responsible for the initiation of PHF formation in vivo. PMID- 7789521 TI - Monomeric human cathepsin E. AB - Cathepsin E is a homodimer, consisting of two monomers linked by an inter molecular disulphide bond. The cysteine residue involved is located near to the N terminus of the mature proteinase. By mutating this residue to alanine, a monomeric form of human cathepsin E was engineered and purified. The activity of the resultant enzyme was not altered significantly (in terms of its ability to hydrolyse two chromogenic peptide substrates; and its susceptibility to inhibition by pepstatin). However, the stability of the mutant enzyme to alkaline pH and to temperature was markedly reduced. PMID- 7789524 TI - NMR studies of the methionine methyl groups in calmodulin. AB - Calmodulin (CaM) is a ubiquitous Ca(2+)-binding protein that can regulate a wide variety of cellular events. The protein contains 9 Met out of a total of 148 amino acid residues. The binding of Ca2+ to CaM induces conformational changes and exposes two Met-rich hydrophobic surfaces which provide the main protein protein contact areas when CaM interacts with its target enzymes. Two-dimensional (1H,13C)-heteronuclear multiple quantum coherence (HMQC) NMR spectroscopy was used to study selectively 13C-isotope labelled Met methyl groups in apo-CaM, Ca(2+)-CaM and a complex of CaM with the CaM-binding domain of skeletal muscle Myosin Light Chain Kinase (MLCK). The resonance assignment of the Met methyl groups in these three functionally different states were obtained by site directed mutagenesis (Met-->Leu). Chemical shift changes indicate that the methyl groups of the Met residues are in different environments in apo-, calcium-, and MLCK-bound-CaM. The T1 relaxation rates of the individual Met methyl carbons in the three forms of CaM indicate that those in Ca(2+)-CaM have the highest mobility. Our results also suggest that the methyl groups of the unbranched Met sidechains in general are more flexible than those of aliphatic amino acid residues such as Leu and Ile. PMID- 7789526 TI - Cloning and controlled overexpression of the gene encoding the 35 kDa soluble lytic transglycosylase from Escherichia coli. AB - The lytic transglycosylases of Escherichia coli are involved in peptidoglycan metabolism and resemble the lysozymes not only in activity, but in the case of the 70 kDa soluble lytic transglycosylase (Slt70), also structurally. Here we report the cloning of the gene that encodes the 35 kDa soluble lytic transglycosylase (Slt35) of E. coli. Based on the sequence of the full-length gene, Slt35 is very likely to be a proteolytically truncated form of a slightly larger protein. The homology between Slt35 and Slt70, albeit poor, indicates that the active site architecture of both proteins may be alike. Using the T-7 promoter system, Slt35 was overproduced in large quantities and purified to homogeneity for crystallographic purposes. PMID- 7789525 TI - The GLUT4 glucose transporter and the alpha 2 subunit of the Na+,K(+)-ATPase do not localize to the same intracellular vesicles in rat skeletal muscle. AB - The GLUT4 glucose transporter and the alpha 2 subunit of the Na+,K(+)-ATPase of rat skeletal muscle are two proteins which redistribute from intracellular membranes to plasma membranes following in vivo insulin stimulation. Here we show that although both proteins co-segregate after subcellular fractionation of unstimulated rat hindlimb muscles, they do not share the same intracellular residence inside the muscle fibre. By immunogold single- and double-labeling on ultrathin muscle cryosections with specific antibodies, the GLUT4 glucose transporter and the Na+,K(+)-ATPase alpha 2 subunit were observed on different vesicular structures within the cell. GLUT4 was detected on subsarcolemmal and perinuclear membranes, and at the junction between myofibrillar A and I bands where triads are localized. The alpha 2 subunit of the Na+,K(+)-ATPase was observed at the plasma membrane and in distinct subsarcolemmal vesicles and intermyofibrillar membranes. Quantitative analysis of double-labeling of GLUT4 and Na+,K(+)-ATPase alpha 2 subunit revealed that less than 6% of the two proteins co-localize in the same continuous vesicular structures. The differential intracellular localization of the two proteins was further confirmed by immunopurification of GLUT4-containing membranes from muscle homogenates, in which the alpha 2 subunit of the Na+,K(+)-ATPase was found only at the same extent as the alpha 1 subunit of the enzyme, a protein exclusively present at the plasma membrane. PMID- 7789527 TI - Underevaluation of complex I activity by the direct assay of NADH-coenzyme Q reductase in rat liver mitochondria. AB - We have shown that the rate of NADH-coenzyme Q reductase in rat liver mitochondria, assayed using the decyl-ubiquinone analog DB, is underevaluated, probably as a result of its low water solubility. In view of drawbacks encountered using other more soluble acceptors in this system, we demonstrate that the most reliable assay of the physiological rate of CoQ reduction by Complex I is the indirect calculation from the total rate of NADH oxidation and the rate of ubiquinol oxidation, using the pool equation of Kroger and Klingenberg [(1973) Eur. J. Biochem. 34, 358-368]. PMID- 7789528 TI - IL-13 and IL-4 share signal transduction elements as well as receptor components in TF-1 cells. AB - IL-13 and IL-4 are growth factors for the human erythroleukemia cell line TF-1. In these cells both cytokines share overlapping binding sites, but the number of sites for IL-13 is half of that for IL-4. Two monoclonal antibodies against the extracellular domain of the IL-4R alpha chain completely abolish the binding of IL-13, although IL-13 does not bind to this chain. Following receptor triggering, IL-13 and IL-4 induce the phosphorylation of a 170 kDa protein, probably the IL-4 induced phosphotyrosine substrate. In addition the phosphorylation of the 170 kDa protein results in its tight association with phosphatidylinositol-3-kinase. PMID- 7789529 TI - L-arginine depletion by arginase reduces nitric oxide production in endotoxic shock: an electron paramagnetic resonance study. AB - Nitric oxide (NO) synthesis was measured in the liver, lung, spleen and kidney of lipopolysaccharide-treated male rats using the nitric oxide spin trap, iron (II) diethyldithiocarbamate (FeDETC2). Nitric oxide formation in vivo was determined by the increase in intensity of the characteristic triplet hyperfine EPR spectrum of [NO-FeDETC2]. Intravenous bovine liver arginase, at a dose which completely depleted circulating arginine, significantly reduced the formation of nitric oxide in these tissues. The general decrease in NO levels was confirmed by the decrease in plasma nitrite levels. These results directly demonstrate that NO formation in endotoxic shock depends on extracellular arginine; depletion of plasma arginine may be a useful therapeutic strategy. PMID- 7789530 TI - The depolarization response element in acetylcholine receptor genes is a dual function E box. AB - All acetylcholine receptor subunit genes contain E boxes and are blocked by membrane depolarization. We have used transfected C2C12 myogenic cells to investigate the response, to electrical stimulation and KCl, of wildtype and mutant regulatory regions of the chick acetylcholine receptor alpha, gamma and delta subunit, and the mouse MLC genes. Point mutations revealed that E boxes function as activating elements targeted by the depolarization signal. These experiments suggest, and insertion of a depolarization response element into an unrelated promoter confirms, that plasma membrane depolarization switches the depolarization response element from an activating to a repressive mode. PMID- 7789531 TI - Cloning and disruption of the YNR1 gene encoding the nitrate reductase apoenzyme of the yeast Hansenula polymorpha. AB - The nitrate reductase gene (YNR1) from the yeast H. polymorpha was isolated from a lambda EMBL3 genomic DNA library. As probe a 350 bp DNA fragment synthesized by PCR from H. polymorpha cDNA was used. By DNA sequencing an ORF of 2,577 bp was found. The predicted protein has 859 amino acids and presents high identity with nitrate reductases from other organisms. Chromosomal disruption of YNR1 causes inability to grow in nitrate. Northern blot analysis showed that YNR1 expression is induced by nitrate and repressed by ammonium. PMID- 7789532 TI - Selective preservation of protein kinase C-zeta in the chemoprevention of azoxymethane-induced colonic tumors by piroxicam. AB - While nonsteroidal anti-inflammatory drugs have been shown to exert preventive effects against the development of colonic tumors in humans and in chemically induced tumors in animal models, the mechanism(s) involved in this phenomenon is unclear. We have recently demonstrated that one such agent, piroxicam, when supplemented (75 ppm) in the diets of rats administered azoxymethane, reduced the incidence of rats bearing tumors. To date, the effects of piroxicam on protein kinase C, a family of serine/threonine kinases which may be intimately involved in the colonic malignant transformation process, have not been examined. It was, therefore, of interest to determine whether piroxicam altered the expression of one or more isoforms of this kinase in these tumors. The present studies demonstrate that dietary piroxicam selectively preserved the expression of protein kinase C-zeta in azoxymethane-induced tumors; suggesting that this is at least one mechanism involved in this agent's chemopreventive actions in this organ. PMID- 7789533 TI - Phosphorothioate oligonucleotides bind in a non sequence-specific manner to the nucleolar protein C23/nucleolin. AB - To design optimal strategies for intracellular delivery of antisense phosphorothioate oligonucleotides, it may be useful to understand their interaction with cellular macromolecules. Nuclear extracts from LOX amelanotic myeloma cells were studied for protein binding to phosphorothioate oligonucleotides using a Southwestern protocol. Multiple nuclear proteins bound to the phosphorothioate oligonucleotides but no detectable protein binding was found to phosphodiester oligonucleotides. The protein with the strongest binding signals was shown by immunoprecipitation to be nucleolar C23/nucleolin, a 110 kDa protein. With glutathione S-transferase/nucleolin fusion protein constructs, the region of nucleolin containing the RNA recognition motifs had binding activity to phosphorothioate oligonucleotides. PMID- 7789534 TI - A stress-associated citrus protein is a distinct plant phospholipid hydroperoxide glutathione peroxidase. AB - A protein whose level is markedly increased upon exposure of cultured citrus cells and whole plants to NaCl, was shown to specifically catalyze the reduction of phosphatidylcholine hydroperoxide in the presence of glutathione. This enzymatic activity was shown to be independent of a similar activity exhibited by glutathione S-transferase in plants. This finding corroborates the significant homology (52%) accounted between the deduced amino acid sequence of the gene encoding for this protein and that of mammalian phospholipid hydroperoxide glutathione peroxidases. While the mammalian enzyme is known and well investigated, this study establishes the presence of this key protein also in plants. PMID- 7789535 TI - Dissociation constants and thermal stability of complexes of Bacillus intermedius RNase and the protein inhibitor of Bacillus amyloliquefaciens RNase. AB - Binase, the extracellular ribonuclease of Bacillus intermedius, is inhibited by barstar, the natural protein inhibitor of the homologous RNase, barnase, of B. intermedius. The dissociation constants of the binase complexes with barstar and its double Cys40,82Ala mutant are about 10(-12) M, only 5 to 43 times higher than those of the barnase-barstar complex. As with barnase, the denaturation temperature of binase is raised dramatically in the complex. Calorimetric studies of the formation and stability of the binase-barstar complex show that the binase reaction with barstar is qualitatively similar to that of barnase but some significant quantitative differences are reported. PMID- 7789536 TI - Interleukin-1 beta antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture. AB - We have investigated the effects of interleukin (IL)-1 beta and IL6 on expression and phenobarbital (PB) induction of ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-deethylase (PROD) activities, as well as on mRNA levels of cytochromes P450 (CYP) 1A, 2B, 2C, 2E and 3A, in rat hepatocytes in primary culture. IL6 slightly antagonized PB-induced PROD activity. Strikingly, IL1 beta strongly inhibited basal EROD and PROD activities, and fully blocked their induction by PB in a dose-dependent fashion. Furthermore IL1 beta completely suppressed PB induction of all CYP mRNAs analyzed. Our results demonstrate that IL1 beta can suppress basal CYP activities, as well as PB-inducible expression of five CYP mRNAs in rat hepatocytes in primary culture. PMID- 7789537 TI - Lack of correlation between mRNA expression and enzymatic activity of the aspartate aminotransferase isoenzymes in various tissues of the rat. AB - Little is known about control of expression of basal levels of the aspartate aminotransferases which are ubiquitous 'house keeping' enzymes in vertebrates. We have measured both mRNA and activity levels for both isoenzymes in various rat tissues as a function of age. Patterns of mRNA expression for the two isoenzymes were similar in a particular tissue about differed widely between tissues. Surprisingly, there was no simple correlation between mRNA levels and specific activities of the enzyme products. We conclude that translation for mRNA for these two isoenzymes is subject to tissue-specific, and in some cases age related, regulation. PMID- 7789538 TI - Detection of a sub-set of polysomal mRNAs associated with modulation of hypusine formation at the G1-S boundary. Proposal of a role for eIF-5A in onset of DNA replication. AB - S phase entry, i.e. start of DNA replication, is a crucial step in proliferation. Inhibition of S phase entry correlates with inhibition of hypusine formation, an event affecting only the eukaryotic initiation factor 5A (eIF-5A). Its hypusine containing sequence was postulated to authorize polysomal utilization of specific transcripts for proteins necessary to enable DNA replication. Using mimosine to reversibly suppress the hypusine-forming deoxyhypusyl hydroxylase (E.C. 1.14.99.29) in cells while differentially displaying their polysomal versus non polysomal mRNA populations, we report the detection and classification of several mRNA species that indeed disappear from and reappear at polysomes in concert with inhibition and disinhibition, respectively, of hypusine formation. Based on initial sequence data, two translationally controlled enzymes, both critical for proliferation, are identified as candicate products of such mRNAs, methionine adenosyltransferase (E.C. 2.5.1.6) and cytochrome-c oxidase (EC 1.9.3.1) subunit I. The existence of such putative hypusine-dependent messenger nucleic acids (hymns) provides the basis for a proposal on their molecular function in onset of multiplication. PMID- 7789539 TI - Complement assembly of two fragments of the streptococcal protein G B1 domain in aqueous solution. AB - We examined the complementation of various pairs of fragments derived from the streptococcal protein G B1 domain by NMR and CD. Most were not associated; however, one pair of fragments (1-40) and (41-56) interacted sufficiently enough to regenerated a stable 1:1 complex, Kd = 9 x 10(-6) M. A 2D-NMR analysis showed that the structure of the complex resembled that of native domain. Here we discuss the complementation from the viewpoint of the folding pathway of the protein. PMID- 7789541 TI - Federal Trade Commission staff concerns with assisted reproductive technology advertising. PMID- 7789540 TI - Assisted fertility using electroejaculation in men with spinal cord injury--a review of literature. AB - OBJECTIVE: To review the effectiveness of rectal probe electroejaculation in terms of pregnancy in treatment of anejaculatory males due to spinal cord injury. The characteristics of electroejaculates also are examined. DATA IDENTIFICATION: All English language studies reporting pregnancies as a result of electroejaculation from men with spinal cord injury and related publications on electroejaculation were identified through MEDLINE search and manual scanning of recent relevant journals. RESULTS: Electroejaculation has become an accepted mode of semen procurement in anejaculatory individuals, with a success rate of approximately 60% to 90% varying among different centers. In general these electroejaculates exhibit high sperm counts but low motility and poor sperm function. Retrograde ejaculation is also common. Pregnancies using electroejaculates have been documented since 1975 in the form of case reports and small series. Assisted reproductive technology recently has been used in conjunction with electroejaculation. Although results are encouraging, pregnancy rates, however, cannot be accurately estimated because of the lack of large series in the literature. CONCLUSIONS: An increasing number of spinal cord injured patients desiring fertility can achieve pregnancy through combined use of electroejaculation and assisted reproductive techniques. Larger series are needed to establish an accurate pregnancy rate. Elucidation by further studies on etiology of sperm dysfunction of these individuals may improve their prognosis. PMID- 7789542 TI - A controlled assessment of the in vitro fertilization performance of British women of Indian origin compared with white women. AB - OBJECTIVE: To compare the reproductive performance of Indian versus white women in IVF. DESIGN: Controlled comparative clinical study. SETTING: In vitro fertilization center based in university department in large tertiary level hospital. PATIENTS: Results from first IVF treatment cycles in 44 Indian patients were compared with results from 88 white patients, matched by age and body mass index, over the same treatment year. The patients were selected from a prospectively collected IVF databank. INTERVENTIONS: Standard luteal-phase start long GnRH analogue regime. Ovarian stimulation with FSH and hMG. Transvaginal ultrasound-guided oocyte recovery. In vitro fertilization and ET following established protocols. MAIN OUTCOME MEASURES: Rates of abandoned cycles, egg retrievals, ETs, clinical pregnancies, miscarriages, and live births were compared in the first IVF treatment cycle. Cumulative pregnancy rates (PRs) over three cycles in the two groups of patients were also compared. RESULTS: More cycles were abandoned in the Indian than in the white group: 22.7% versus 9.1%. The Indian live birth rate per cycle was worse: 9.1% versus 22.7%. The performance of the two groups was otherwise similar: ovarian stimulation with hMG and FSH required 26.0 required 26.0 ampules in the Indian group versus 24.6 ampules in the white group, mean number of follicles on the day of egg retrieval 8.7 versus 8.7, mean number of eggs 5.9 versus 5.8, fertilization rate 82.4% versus 82.5%; ET rate 73.5% versus 82.5, mean number of embryos transferred 2.1 versus 1.8, and clinical PR per cycle started 18.2% versus 27.3%. CONCLUSIONS: Under the same IVF regime, Indians performed worse than whites at the stage of ovarian stimulation (higher rate of abandoned cycles for poor response) and in live birth rate. Cumulative conception and live birth rates also tended to be worse in Indians than in whites. PMID- 7789543 TI - High-order oocyte transfer in gamete intrafallopian transfer patients 40 or more years of age. AB - OBJECTIVE: To analyze whether a policy of high-order oocyte transfer would be effective in women > or = 40 years of age who are undergoing GIFT, and further, whether a specific subgroup of these patients could be identified where clinical pregnancy was more likely to occur. DESIGN: Prospective descriptive study. SETTING: Patients in a university-based reproductive endocrinology and infertility practice. PATIENTS: Infertile women > or = 40 years of age who underwent GIFT cycles between January, 1990 and December, 1993 after not having achieved pregnancy with at least three previous cycles of superovulation and intrauterine insemination. INTERVENTIONS: Gamete intrafallopian transfer was performed after controlled ovarian hyperstimulation with hMGs. High-order oocyte transfer was employed. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs). RESULTS: The overall clinical PR was 24.5% per retrieval (12/49) and 25.5% per transfer (12/47). A significantly higher number of oocytes were retrieved in patients who became pregnant than those who did not. Patient age, cycle day 3 FSH level, E2 level on the day of hCG administration, number of oocytes transferred, and total number of motile sperm transferred did not differ significantly between the two groups. The clinical PR per transfer was significantly higher in patients with more than five oocytes transferred (10/27, 37%) versus those with five or less oocytes transferred (2/20, 10%). No multiple gestations were obtained. CONCLUSION: The number of oocytes retrieved in women > or = 40 years of age undergoing GIFT is the main determinant predicting clinical pregnancy. High-order oocyte transfer seems to lead to a favorable PR while the risk of multiple gestation is limited. PMID- 7789544 TI - Pregnancy in women 50 or more years of age: outcomes of 22 consecutively established pregnancies from oocyte donation. AB - OBJECTIVE: To describe the reproductive and obstetric outcomes of women > or = 50 years attempting pregnancy using donor oocytes. SETTING: The IVF program at the University of Southern California. PATIENTS: Thirty-six postmenopausal women aged 50 to 59 years, mean 52.3 +/- 2.6 years (mean +/- SD) were screened medically, reproductively, and psychologically and enrolled in a trial of oocyte donation. INTERVENTIONS: Recipients underwent hormone replacement therapy using oral micronized E2 and IM administered P. Oocytes were provided by designated gamete donors (mean age 30.5 +/- 4.4 years). Embryos (4.3 +/- 1.2) were transferred transcervically. MAIN OUTCOME MEASURES: Rates for embryo implantation, spontaneous abortion, ongoing and delivered pregnancies, as well as the gestational age at delivery, birthweights, complications, and postpartum outcomes. RESULTS: Forty-five aspirations resulted in 22 pregnancies (48.9%): 3 preclinical, 2 ending in spontaneous abortion, and 17 viable pregnancies (37.8%). The embryo implantation rate was 20.6%. Nine of 17 pregnancies (52.9%) were multiple gestations (6 twins; 1 triplet; and 2 quadruplets, selectively terminated to twins). All pregnancies delivered beyond 32 weeks: mean gestational age for singletons was 38.4 +/- 1.9 weeks (range 35 to 41 weeks); mean gestational age for twins was 36.3 +/- 1.4 weeks (range 34 to 38 weeks); the triplet pregnancy delivered at 32 weeks. Complications occurred in eight patients; gestational hypertension (n = 7), preterm labor (n = 3), gestational diabetes (n = 2), and pre-eclampsia (n = 1). One infant was trisomy-21. CONCLUSION: Patients > or = 50 years experience similar pregnancy rates after oocyte donation as younger women and are at equal risk for multiple gestation. Antenatal complications were experienced by the majority of patients, underscoring the importance of high risk obstetric surveillance and care. PMID- 7789545 TI - Fertilization and pregnancy with acrosome intact sperm by intracytoplasmic sperm injection in patients with disordered zona pellucida-induced acrosome reaction. AB - OBJECTIVE: To determine whether fertilization and pregnancy could be obtained by injection of acrosome-intact sperm into the cytoplasm in patients with persistent failure of fertilization in IVF-ET associated with disordered zona pellucida (ZP) induced acrosome reaction (AR). DESIGN: Sperm-ZP binding and penetration and ZP induced AR were compared between patients and fertile donors. Acrosome-intact sperm removed from the ZP were injected into the cytoplasm of the oocytes. SETTING: Reproductive Biology Unit, Royal Women's Hospital. MAIN OUTCOME MEASURES: The proportion of ZP penetrated and ZP-induced AR and fertilization and pregnancy after intracytoplasmic sperm injection were analyzed. RESULTS: Most (7/8) of the patients had consistently normal sperm characteristics including concentration, motility and velocity, acrosomes, and morphology. Mean number of sperm bound to the ZP was not significantly different between patients (97 sperm/ZP) and fertile donor controls (100 sperm/ZP). However, AR of sperm bound to the ZP was significantly lower in the patients (4%) than in controls (61%). None of the ZP (n = 32) were penetrated by patient sperm whereas all (n = 32) ZP were penetrated by control sperm. Acrosome intact sperm removed from the ZP were used for intracytoplasmic sperm injection. All patients had > or = 50% normal fertilization and embryo development. Three pregnancies (one early aborted, two ongoing) were achieved after the transfer of fresh or frozen embryos. CONCLUSION: Acrosome-intact human sperm can produce a high fertilization rate and pregnancies after intracytoplasmic sperm injection in patients with disordered ZP-induced AR. The acrosome reaction is unlikely to be important for fertilization with intracytoplasmic sperm injection. PMID- 7789546 TI - The use of zona-free aged unfertilized human oocytes as a predictor for successful subzonal insemination. AB - OBJECTIVE: To examine the reliability of the zona-free aged (1 day old) human unfertilized oocyte sperm penetration assay for assessing sperm fertilizing ability and to determine the predictive value of this assay for subsequent subzonal insemination (SUZI) outcomes. DESIGN: A total of 253 unfertilized oocytes from total fertilization failure patients and from good fertilization rate (> 70%) patients in standard IVF were inseminated with donors' spermatozoa, and penetration rates were compared in each group. Two hundred seventy-two unfertilized oocytes from total fertilization failure, poor fertilization (< 30%), and normal fertilization (> 30%) were inseminated with husbands' spermatozoa, and penetration rates were compared between the three groups. In 29 patients, the results of the zona-free assay performed in previous IVF were compared with the fertilization rates of subsequent SUZI. RESULTS: In the zona free assay using donors' spermatozoa, there was no difference in penetration rates between the two groups (109/122, 89.3% versus 114/131, 87.0%). Penetration rates using partners' spermatozoa were positively correlated with fertilization rates in standard IVF (total fertilization failure 34/75, 45.3%; poor fertilization 56/77, 72.7%; normal fertilization 108/120, 90.0%). There was a significant difference in fertilization rates after SUZI between the patients with negative and positive penetration in zona-free assay (4/53, 7.5%, versus 54/174, 31.0%). CONCLUSION: The zona-free human oocyte assay may primarily reflect sperm fertilizing ability. This asssay also could be a reliable predictor for subsequent SUZI outcome. PMID- 7789547 TI - High progesterone levels adversely affect embryo quality and pregnancy rates in in vitro fertilization and oocyte donation programs. AB - OBJECTIVE: To assess the effect of P levels on oocyte and embryo quality and pregnancy rates (PRs) in IVF and oocyte donation. DESIGN: Retrospective analysis of PRs in ovum donors and their recipients with regard to P levels on day of hCG administration. SETTING: In Vitro Fertilization Units, oocyte donation programs. PATIENTS: In vitro fertilization patients who agreed to donate oocytes were treated by hMG alone (53 cycles) or in combination with a GnRH analog (122 cycles). INTERVENTIONS: Uterine preparation in oocyte recipients consisted of 6 mg/d E2 valerate. Progesterone (100 mg/d) was added when oocytes became available. Hormonal treatment was continued until 12 weeks of gestation. RESULTS: Using a series of Fisher's Exact Tests, a critical threshold for P was identified at 1.9 ng/mL (conversion factor to SI units, 3.185). With elevated P levels (> 1.9 ng/mL), lower PRs were noted for the donors (7.1% versus 17%), as well for the recipients (8.3% versus 26.7%). CONCLUSIONS: Exposure to elevated P levels resulted in lower PRs for the donors and significantly lower PRs in the recipients. Because the endometria in the recipients were prepared uniformly, we conclude that this is the result of detrimental effects of P on oocyte or embryo quality. PMID- 7789548 TI - Assisted reproductive technology in the United States and Canada: 1993 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. AB - OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive technology (ART) initiated in the United States in 1993. DESIGN: Data were collected on an annual summary form and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANTS: Two hundred sixty-seven programs submitted data on procedures performed in 1993. Data were collected in October 1994 so that outcome of all pregnancies established would be known. MAIN OUTCOME MEASURES: The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, and congenital abnormality. RESULTS: Programs reported initiations of 41,209 cycles of ART treatment, excluding frozen embryo and donor oocyte cycles. Of these, 33,543 cycles initiated were IVF (standard, with micromanipulation, and for host uterus transfer) with 18.3% deliveries per retrieval; 4,992 were cycles of GIFT with 28.1% deliveries per retrieval; 1,792 were cycles of ZIFT with 24.4% deliveries per retrieval; and 882 were combination cycles, combining IVF and one of the tubal transfer techniques, resulting in 27.8% deliveries per retrieval. In addition to these cycles initiated in 1993, 6,869 frozen ET procedures were reported, either as separate procedures or in combination with another ART procedure with 13.3% deliveries per procedure, and 2,766 donor oocyte cycles were initiated with an overall success of 30.2% deliveries per retrieval. As a result of all procedures, a total of 8,741 deliveries were reported. CONCLUSIONS: In 1993, there were more programs offering more treatment cycles of ART. Overall average success rates (deliveries per procedures) exhibited only a small increase compared with previously reported summaries. PMID- 7789549 TI - Extracellular matrix interactions in early human embryos: implications for normal implantation events. AB - OBJECTIVE: To study the role of the extracellular matrix (ECM) proteins in supporting the development and implantation competence of human embryos. DESIGN: Expression of an implantation site adhesive glycoprotein, oncofetal fibronectin, and basement membrane collagen-degrading matrix metalloproteinase-2 and -9 were studied in cultured human embryos. The ability of exogenously added laminin and fibronectin to enhance hatching and matrix metalloproteinase-2 expression was quantitated also. PATIENTS: Fifty-four women with tubal factor infertility enrolled in the IVF program at the University Hospital of Oulu agreed to participate by providing 20 residual oocytes and 227 residual early embryos for this study. MAIN OUTCOME MEASURES: The presence of oncofetal fibronectin immunoreactive protein was assayed by immunocytochemical staining with two specific monoclonal antibodies, FDC-6 and X18A4. These antibodies bind to specific and distinct epitopes within tumor and trophoblast-derived oncofetal fibronectin. Changes in embryo matrix metalloproteinase-2 production were measured by zymography and confirmed by immunocytochemical staining. RESULTS: Intracellular oncofetal fibronectin was identified within blastomeres of early stage embryos. The immunoreactivity of oncofetal fibronectin in the zona pellucida was associated with fragmentation and dissolution of the zona. Exogenously added laminin or adult-type fibronectin significantly increased the hatching rate of the cultured embryos. Embryos cultured with added adult-type fibronectin or trophoblast-derived oncofetal fibronectin stimulated the matrix metalloproteinase-2 production (72-kd type IV collagenase) by 2.25 +/- 0.16-fold when compared with control embryos (mean +/- SD). CONCLUSIONS: Embryonic production of specific ECM proteins, such as oncofetal fibronectin, appears to be important for the morphological and biochemical development of human preimplantation embryos. Moreover, ECM proteins promote acquisition of the adhesive and degradative properties required by human embryos for successful implantation. PMID- 7789551 TI - Pentoxifylline improves sperm binding to the zona pellucida in the hemizona assay. AB - OBJECTIVE: To evaluate the effect of pentoxifylline on sperm binding capacity to zona pellucida (ZP) using the hemizona assay (HZA). DESIGN: The fertility potential of 82 men was evaluated by routine semen analysis. Each ejaculate was incubated with or without pentoxifylline (3 mM) in Ham's F-10 medium (Flow Laboratories, Irvine, Scotland) before the HZA. The effect of the pentoxifylline treatment on sperm-binding capacity to ZP was assessed by the hemizona index. RESULTS: The mean hemizona indexes with medium or pentoxifylline treatment were 23% +/- 2.1% (mean +/- SE) and 41% +/- 3.4%, respectively. Taking into consideration a significant change of the hemizona index on rising above the intra-assay coefficient of variation (+/- 8%) after pentoxifylline treatment, 73.1% of specimens improved, 19.5% deteriorated, and 7.4% remained unchanged. Using a threshold hemizona index of 23% as a discriminator between fertile and infertile specimens, 43.5% of the "pentoxifylline-improved" samples ascended to the fertile zone (> 23%). No correlations were found between sperm variables in the raw semen and the effect of pentoxifylline on sperm binding capacity. CONCLUSION: Pentoxifylline may improve the binding capacity of human spermatozoa. However, this effect is confined to a selected group of patients and cannot be predicted by the basic sperm variables. Thus, to avoid uncertain or damaging effects of pentoxifylline while preparing sperm suspension for assisted reproductive techniques, it is recommended that its effect be tested by the HZA system before its use. PMID- 7789550 TI - Dose effects of the gonadotropin-releasing hormone antagonist, Nal-Glu, combined with testosterone enanthate on gonadotropin levels in normal men. AB - OBJECTIVE: To test the hypothesis that over a 4-week treatment period, Nal-Glu GnRH antagonist ([AcD2Nal1, D4ClPhe2, D3Pal3, Arg5, DGlu6 [AA], DAla10] GnRH) at a dose of 200 micrograms/kg per day SC would suppress levels of immunologically active and biologically active LH and FSH more completely than a dose of 100 micrograms/kg per day. DESIGN: Placebo controlled clinical study. SETTING: A university community. SUBJECTS: Thirty normal male volunteers. INTERVENTIONS: We administered Nal-Glu at doses of 0, 100, and 200 micrograms/kg body weight per day in combination with T enanthate, 50 mg IM weekly, to separate groups of men (9 or 10 men per group) for 4 weeks. RESULTS: Serum levels of immunologically active and biologically active gonadotropins were suppressed similarly in both groups of men who received Nal-Glu; this suppression was significantly greater than in the men who received placebo + T. Local side effects were more severe in the Nal-Glu 200 micrograms/kg per day group. CONCLUSIONS: Administration of Nal Glu in combination with T suppresses gonadotropins more completely than does T alone, but at doses > 100 micrograms/kg, gonadotropins are not suppressed additionally with larger doses of Nal-Glu. Subjects experienced greater local discomfort and side effects with the higher dosage. These findings suggest that dosages of Nal-Glu of > 100 micrograms/kg per day may have no advantage over the 100-micrograms/kg dose in a male contraceptive regimen. PMID- 7789552 TI - Spermatozoa selected by a discontinuous Percoll density gradient exhibit better motion characteristics, more hyperactivation, and longer survival than direct swim-up. AB - OBJECTIVE: To determine if a discontinuous Percoll density gradient selects spermatozoa with different motion characteristics than direct swim-up. DESIGN: Controlled prospective study of the effect of two preparation techniques on spermatozoa from normal semen samples using computer-aided sperm analysis (CASA). SETTING: The Fertility laboratory, Queen Charlotte's Hospital, London, United Kingdom. PATIENTS: Eighteen male patients. INTERVENTIONS: Semen samples were divided into two equal parts. The first part was prepared by a direct swim-up whereas the other half was subjected to a three-layer discontinuous Percoll density gradient centrifugation. The separated samples were then examined at 30 minutes and 3, 6, and 24 hours by CASA. RESULTS: Although swim-up selected a higher proportion of motile spermatozoa, Percoll produced a greater yield of motile cells. Straight line velocity was similar for both methods throughout study. In contrast, spermatozoa isolated by Percoll exhibited a significantly higher curvilinear velocity and amplitude of lateral head displacement, which lasted for > or = 6 hours. These changes were accompanied by a significant reduction in linearity of progression. The most dramatic effect of Percoll was to produce significantly greater numbers of spermatozoa expressing hyperactivation. After both swim-up and Percoll there was a decline in progressive motility over the 24 hours, although this was only significant for swim-up. CONCLUSIONS: In normal semen, a discontinuous Percoll density gradient selects spermatozoa with better motion characteristics, more hyperactivation, and improved longevity compared with direct swim-up. In view of the relationship between sperm motion characteristics and fertilizing ability, we conclude that the three-layer discontinuous Percoll density gradient be adopted as the preferred method for the preparation of spermatozoa for assisted reproduction. PMID- 7789553 TI - Oxidative stress and interleukins in seminal plasma during leukocytospermia. AB - OBJECTIVE: To quantify the levels of reactive oxygen species, superoxide dismutase (SOD), and interleukins (IL) 2 and 8 in seminal plasma of infertile patients as well as to examine the possible relationship between oxidative stress and proinflammatory cytokines. DESIGN: Semen collected from normal fertile donors, infertile men without symptoms of genitourinary (GU) inflammation, and infertile men with symptoms of infection-inflammation of the GU tract was evaluated for the levels of granulocyte elastase, reactive oxygen species, SOD, IL-2, and IL-8. Any correlation between the levels of reactive oxygen species and other parameters in these population was analyzed statistically. RESULTS: Significantly high levels of granulocyte elastase (18.32 +/- 1.52 U/L), reactive oxygen species (6 x 10(5) cpm), IL-8 (3.7 +/- 0.10 microgram/L), and IL-2 (18.32 +/- 1.47 ng/L) were observed in semen of infertile patients with leukocytospermia compared with the other two groups. In leukocytospermic samples, the activity of SOD was significantly lower (624.89 +/- 41.16 NU/mL) compared with nonleukocytospermic samples (787.85 +/- 24.26 NU/mL) or fertile donors (816.29 +/ 50.16 NU/mL). A significant positive correlation was observed between the levels of reactive oxygen species and IL-8. CONCLUSIONS: These findings suggest that increased oxidative stress observed during leukocytospermia may modulate the level of proinflammatory cytokines. The increased oxidative stress may be due to a defect in the reactive oxygen species scavenging system. PMID- 7789554 TI - The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis). AB - OBJECTIVE: To test the hypothesis that immunosuppression increases the development and progression of endometriosis in baboons. DESIGN: Experimental controlled study. SETTING: Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS: Thirty-two baboons (8 with normal pelvis, 10 with spontaneous endometriosis, and 14 with endometriosis induced by intraperitoneal seeding of menstrual endometrium). INTERVENTION: Daily injection of 0.8 mg/kg IM methylprednisolone and 2 mg/kg azathioprine for 3 months in 16 baboons (4 with normal pelvis, 5 with spontaneous endometriosis, and 7 with induced endometriosis). No treatment was given to the remaining 16 primates. MAIN OUTCOME MEASURES: The change in number and surface area (mm2) of endometriotic lesions was evaluated by laparoscopy in all baboons after 3 months, in 8 animals with induced endometriosis and in 9 primates with spontaneous disease after 7 and 12 months, respectively. RESULTS: Immunosuppressed baboons with spontaneous endometriosis had a significantly higher number and larger surface area of endometriotic lesions than nontreated animals. However, immunosuppressed and nontreated primates with induced endometriosis were comparable with respect to both number and surface area of implants. A transient decrease in typical lesions was noted during immunosuppression. Immunosuppression did not cause the development of endometriosis in baboons with previously documented normal pelvis. CONCLUSION: Immunosuppression may increase the progression of endometriosis in baboons with spontaneous disease. PMID- 7789556 TI - A new selection criterion for fimbriectomy reversal. AB - OBJECTIVE: To assess a new criterion for selection of patients who request reversal of fimbriectomy sterilization. DESIGN: Prospective study. SETTING: Division of reproductive endocrinology and infertility in an academic center. PATIENTS: Eight patients undergoing reversal of fimbriectomy using microsurgical techniques. The prerequisite inclusion criterion was the presence of more than 50% ampulla as shown at hysterosalpingography. This is easily determined, because the isthmic length approximates one half the ampullary length. RESULTS: The cumulative intrauterine pregnancy rate was 50%. There were no ectopic pregnancies. CONCLUSION: Similar pregnancy rates for reversal of fimbriectomy have been reported based upon different absolute selection criteria (viz., tubal length of > or = 8 cm and ampullary width of > or = 1 cm). By contrast, our new selection criterion is based upon the more readily determined proportion of ampulla that is available for surgical neostomy. PMID- 7789555 TI - Development of a new alloplastic spermatocele demonstrating successful sperm retrieval in an animal model. AB - OBJECTIVE: To create an alloplastic spermatocele capable of repeated sperm aspiration. The alloplastic spermatocele has long been a theoretical solution to infertility for those patients with congenital absence of the vas deferens or irreversible obstruction of the male reproductive ductal system. Recent studies have suggested that sperm from efferent ducts are capable of fertilization. Clinical use of alloplastic spermatoceles for collection of epididymal sperm has resulted in unacceptably low pregnancy rates. Improvement in spermatocele function may occur if a microsurgical anastomosis is performed to the epididymis. DESIGN: A newly designed alloplastic spermatocele was implanted in 17 mature male rabbits. The faceplate of the device had a 0.7-mm orifice, allowing direct precise microsurgical anastomosis to a specific loop of the epididymal tubule. RESULTS: Sperm retrieval was possible in 16/17 (94%) animals. Repeated successful aspirations (total of 73) were performed in all but one animal. The total number of sperm collected per spermatocele averaged 115 x 10(6) (range 0 to 734 x 10(6)). The sperm motility varied widely between animals and specimens, with a maximum average of 21.6% motile sperm/aspirate per animal. All spermatoceles eventually occluded (mean time of occlusion 14 days; range 3 to 30 days). The prostheses with the attached epididymides were examined histologically. CONCLUSIONS: This prototype alloplastic spermatocele allows repeated high density sperm retrieval over a short period of time. Low sperm motility may be less problematic clinically as new techniques of IVF become available. PMID- 7789557 TI - Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect. AB - OBJECTIVE: To study the response of uterine leiomyomata to three daily doses of RU486 (5, 25, and 50 mg). DESIGN: Prospective nonrandomized trial of women with symptomatic leiomyomata. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS: Ten patients with symptomatic leiomyomata previously reported after treatment with 50 mg of RU486 daily for 3 months. Eleven patients treated with 25 mg of RU486 daily and nine patients placed on 5 mg of RU486 daily for 12 weeks. MAIN OUTCOME MEASURES: Changes in leiomyomata volume as measured with vaginal ultrasounds at baseline and monthly thereafter. Frequent blood samples for hematology, chemistry, and hormone levels were obtained. Twenty-four-hour urine collections for free cortisol and creatinine were obtained at baseline and at 12 weeks. RESULTS: All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% +/- 4.8% of baseline at 4 weeks, 60.5% +/- 6.6% at 8 weeks, and 51.0% +/- 9.2% after 12 weeks of treatment. Regressive response in patients treated with 25 mg of RU486 daily was 76.3% +/- 5.0% of baseline at 4 weeks, 54.0% +/- 5.1% at 8 weeks, and 44.0% +/- 5.0% after 12 weeks. At 5 mg of RU486 leiomyomata volume was 80.6% +/- 8.3% of baseline after 4 weeks, 63.7% +/- 14.6% after 8 weeks, and 74.4% +/- 19.8% after 12 weeks of therapy. CONCLUSIONS: Although acyclicity is seen at all three doses, an effective dose to cause a clinically significant (50%) decrease in leiomyomata volume appears to be 25 mg daily. PMID- 7789558 TI - Fibroid growth in response to high-dose progestogen. AB - OBJECTIVE: To challenge the conventional belief that leiomyomata are estrogen dependent tumors by presentation of a case report suggesting high-dose progestogen therapy is associated with a dramatic increase in size of a fibroid uterus. DESIGN: Case report. SETTING: British university hospital. PATIENT: One white woman treated with tamoxifen and high-dose megestrol acetate for breast carcinoma. INTERVENTIONS: Megestrol acetate therapy withdrawn. MAIN OUTCOME MEASURE: Uterine size. RESULTS: While taking tamoxifen and high-dose megestrol acetate, the patient suffered a dramatic increase in size of her fibroid uterus, which reversed when the progestogen was withdrawn. CONCLUSION: This case report suggests that P may be important in fibroid growth. PMID- 7789559 TI - Subendometrial contractility in menstrual phase visualized by transvaginal sonography in patients with endometriosis. AB - OBJECTIVE: To describe the propagation direction of the subendometrial myometrial contractile wave in menstrual phase sonographically assessed in patients with and without endometriosis. DESIGN: Prospective study. SETTING: Patients and normal volunteers in a university hospital. PATIENTS: Sixteen women with (study group) and 21 without (control group) endometriosis. INTERVENTIONS: Patients were examined by transvaginal sonography (midsaggital plane of the uterus) and recorded on videotape for a 5-minute period. MAIN OUTCOME MEASURE: Direction of propagation of contraction waves. RESULTS: The endometriosis group showed a predominant retrograde pattern whereas the control group showed a normal antegrade. CONCLUSION: This abnormal cervix-to-fundus myometrial activity could well increase the amount of peritoneal shedding of endometrial menstrual debris, increasing the probabilities of its heterotopic implantation. PMID- 7789561 TI - Toward reducing risks and costs of egg donation: a preliminary report. AB - OBJECTIVE: To use clomiphene citrate for ovarian stimulation of egg donors as a means of reducing the risk, discomfort, and inconvenience for egg donors and reducing costs for recipients. DESIGN: Prospective nonrandomized clinical study. SETTING: Private reproductive center. PATIENTS: Egg donation recipients and their anonymous donors. INTERVENTION: Clomiphene citrate was administered to egg donors rather than a GnRH agonist and gonadotropins before oocyte retrieval. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Eleven oocyte retrievals were performed and conception occurred in four cycles, three of which delivered. CONCLUSION: Clomiphene citrate appears to be a reasonable less expensive method of ovarian stimulation for egg donation in normospermic males and appears more acceptable to potential donors. PMID- 7789560 TI - Semen leukocytes: friends or foes? AB - OBJECTIVE: To test the hypothesis that male reproductive tract leukocytes function in the elimination of abnormal spermatozoa from ejaculated semen. DESIGN: Semen specimens with > or = 2 x 10(6) nonspermatozoal cells/mL were examined for leukocytes and for mature sperm with ideal morphology. SETTING: Andrology laboratory of a Center of Assisted Reproductive Technology. RESULTS: Semen specimens with elevated concentrations of leukocytes contained a significantly higher frequency of sperm with ideal morphology than semen specimens with elevated numbers of immature germ cells and low numbers of leukocytes. CONCLUSIONS: The direct correlation between leukocyte density and sperm with ideal morphology supports the concept that sperm surveillance is a normal function of male reproductive tract leukocytes. Understanding such germ cell-leukocyte interactions may provide valuable new insights into immunologic control mechanisms in male reproductive tract tissues. PMID- 7789562 TI - Polycystic kidney disease and infertility. AB - OBJECTIVE: To analyze the cause of infertility in a patient with polycystic kidney disease. SETTING: General hospital. PATIENT: A 32-year-old man known with adult polycystic kidney disease, complaining of infertility and testicular pain. INTERVENTIONS: Testicular biopsy; imaging. RESULTS: Examination revealed bilateral severe congestion of the epididymis. The semen contained no spermatozoa and practically no fructose. Testicular biopsy, however, showed normal spermatogenesis. Transrectal ultrasonography and computer tomography revealed severe congestion and extensive cystic changes in the seminal vesicles. CONCLUSION: The dilated cysts in the seminal vesicles had led to obstructive azoospermia, probably through compression of the ductal system. PMID- 7789563 TI - Laparoscopic sterilization in the supine position using the Ramathibodi uterine manipulator. AB - OBJECTIVES: To investigate the usefulness of the Ramathibodi uterine manipulator (AMZURA Enterprises, Freeport, NY) in performing laparoscopic sterilization procedures in the supine position under local anesthesia. DESIGN: Descriptive prospective study. SETTING: Ambulatory surgical unit of university-affiliated hospital. PATIENTS: Women presenting for elective sterilization and weighing < 110 kg. INTERVENTION: The Ramathibodi uterine manipulator was used to provide uterine manipulation in 85 cases of laparoscopic sterilization, all performed in the supine position as local anesthesia-sedation sterilization operations. Because such procedures are becoming more common worldwide, we propose the acronym "LASSO" (Local Anesthesia-Sedation Sterilization Operation) for this class of operations. Although commonly used in minilaparotomy procedures, use of this uterine manipulation device in laparoscopic procedures has not been published previously. MAIN OUTCOME MEASURE: Successful tubal occlusion. RESULTS: Among the 85 cases reported here there were no failures to manipulate the uterus successfully, to identify the tubes, and to occlude them. CONCLUSIONS: The simplicity of the Ramathibodi uterine manipulator provided several advantages over other means of uterine manipulation, notably [1] constant easy-to-learn maneuvers, [2] no tenaculum or balloon requirement, [3] the procedure could be performed in the supine position, and [4] there are no working parts, screws, or springs that could be lost or broken by operating room staff. Our experience with this device leads us to recommend it to colleagues as an inexpensive, safe, and effective alternative to currently available instruments for providing uterine elevation during laparoscopic sterilization procedures. PMID- 7789565 TI - Recombinant follicle-stimulating hormone and luteinizing hormone--mimicking nature and beyond. PMID- 7789564 TI - Repeatability of measurements on human, rabbit, and bull sperm by computer assisted sperm analysis when comparing individual fields and means of 12 fields. AB - OBJECTIVE: To compare repeatability of measurements of human, rabbit, and bull sperm on two Hamilton Thorne Integrated Visual Optical System (IVOS) units, software version 10. DESIGN: Semen samples from seven normal human subjects, six rabbits, and eight bulls were obtained at regular intervals. The samples were diluted, two chambers were filled, and 12 fields were recorded, using high resolution recorders. Computer-assisted sperm analysis (CASA) was performed nearly simultaneously with two Hamilton Thorne IVOS units. SETTING: Reproduction Research Laboratories, Cornell University and Hamilton-Thorne Research, Beverly, Massachusetts. RESULTS: Optimal settings were established for evaluating by CASA sperm from three species. Fifteen variables were analyzed. The correlation coefficients for most variables characterizing sperm motion and concentration, when means of 12 fields were calculated, were 0.95 to 1.00. There were too few hyperactive sperm to obtain a reliable correlation for human sperm (r = 0.63) and repeatability of elongation was lower only for human sperm (r = 0.75). CONCLUSIONS: Two units of Hamilton Thorne IVOS, software version 10, were capable of providing nearly identical estimates of many CASA variables of human, rabbit, and bull sperm. Correlations for the paired estimates of many motion characteristics and sperm concentration usually exceeded 0.97. PMID- 7789566 TI - New frontiers in the treatment of male infertility. PMID- 7789567 TI - "Leaky randomization" standard practice--but is it correct? PMID- 7789568 TI - Fluorescence in situ hybridization aficionados and rater variation. PMID- 7789569 TI - The prognosis for live birth among untreated infertile couples. AB - OBJECTIVE: To estimate the likelihood of live birth and the impact of prognostic factors among untreated infertile couples. DESIGN: Cohort follow-up study. SETTING: Eleven infertility clinics in academic medical centers. PATIENTS: Two thousand one hundred ninety-eight couples with infertility of > 1 year in duration. Untreated months of observations on 873 untreated couples (18,364 months) were combined with observations before the first treatment among 1,325 treated couples (9,761 months). INTERVENTIONS: Diagnostic tests as indicated. MAIN OUTCOME MEASURES: Time to conception for live birth; effect of baseline characteristics estimated by means of proportional hazards analysis. RESULTS: There were 263 live birth conceptions during 28,125 months of untreated observations. The cumulative rate of conceptions leading to live birth was 14.3% at 12 months. The relevant prognostic factors were pregnancy history, duration of infertility, female partner's age, male defect, endometriosis, and tubal disease. A prediction score based on these factors would be accurate in approximately 62% of cases. CONCLUSIONS: The estimation of live birth among untreated infertile couples is sufficiently accurate to be useful in the clinical management of infertility and in the planning of clinical trials. PMID- 7789570 TI - "Part of the primordial soup". PMID- 7789572 TI - Screening for ovarian reserve. PMID- 7789571 TI - Outpatient hysteroscopy--paracervical block. PMID- 7789573 TI - Intracytoplasmic sperm injection--"pushing the envelope". PMID- 7789574 TI - Endometriosis and gamete intrafallopian transfer. PMID- 7789575 TI - Terminology for luteinizing hormone-releasing hormone antagonists. PMID- 7789576 TI - Killer cell activity, statistics, and endometriosis. PMID- 7789577 TI - Predictors of success of reversal of sterilization. AB - OBJECTIVE: To determine the prognostic variables effecting the successful pregnancy outcome of reversal of sterilization. DESIGN: Demographic and clinical history data were collected prospectively. SETTING: Division of Infertility and Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada. PATIENTS AND INTERVENTION: Between 1981 and 1992, 217 consecutively referred patients underwent reversal of sterilization by a single surgeon using microsurgical techniques. MAIN OUTCOME MEASURES: Prognostic variables associated with success were examined using logistic regression and expressed as odds ratios with corresponding 95% confidence intervals. RESULTS: Age at reversal was a significant factor with the odds of a successful outcome for those < or = 35 years compared with those > 35 years being 2.3 with a 95% confidence interval of 1.3 to 4.1. There was some evidence that average tubal length as categorized in 2-cm intervals was a significant prognostic factor with the odds of a successful outcome for those with an average length of > 4 cm to those < or = 4 cm being 5.3 with a 95% confidence interval of 1.4 to 20.0. CONCLUSIONS: Nonsubjective analysis of the prognostic variables of reversal of sterilization associates only age and tubal length of > 4 cm with intrauterine pregnancy. PMID- 7789578 TI - Decremental follicle-stimulating hormone and dominant follicle development during the normal menstrual cycle. AB - OBJECTIVE: To study the relationship between decreasing serum FSH levels in the follicular phase of the normal menstrual cycle and follicle development by means of transvaginal sonography and E2 production. DESIGN: Daily blood samples were taken and transvaginal sonography was performed every other day in 16 normal regularly cycling female volunteers. MAIN OUTCOME MEASURE: Serum levels of FSH, LH, E2, and P and follicle diameter by transvaginal sonography. RESULTS: A distinct variability in individual maximal early follicular phase FSH plasma levels was observed (range 4.4 to 11.2 mIU/mL [conversion factor to SI unit, 1.000]). Differences in maximum FSH levels did not correlate with other endocrine or sonographic follicular phase characteristics. The follicular phase FSH decrease (from median 6.6 to 2.9 mIU/mL [conversion factor to SI unit, 1.000]) took place between cycle day 5 and 13 and was linear (0.5 +/- 0.05 mIU/mL per day; mean +/- SD). A significant correlation was found between serum FSH decrease and E2 increase. The day of sonographic appearance of a dominant follicle (median cycle day 8) did correlate with the first rise of the E2 plasma concentration. CONCLUSIONS: The present study suggests that even in women exhibiting normal ovarian function a 2.5-fold difference in FSH threshold concentrations for follicle recruitment does occur. Moreover, the magnitude of decrease in serum FSH concentrations during the follicular phase affects dominant follicle E2 production. The sonographic appearance of the dominant follicle is associated with a rise in serum E2 levels. PMID- 7789579 TI - Evaluation of cytogenetic analysis for clinical preimplantation diagnosis. AB - OBJECTIVE: To evaluate the feasibility of using cytogenetic analysis in preimplantation diagnosis. DESIGN: Two different biopsy protocols (chemical drilling and zona cutting) and two fixation methods were tested in a mouse model. Afterwards, the efficiency of obtaining chromosome preparations from untransferable human embryos depending on the method used to obtain the blastomeres (embryos biopsy or removal of the zona pellucida and blastomere disaggregation) was determined. The chances of obtaining chromosome preparations depending on the type of embryo (haploid, diploid, triploid, and apparently unfertilized) were also evaluated. RESULTS: Results from the mouse model showed that chemical drilling yields better results than cutting in terms of metaphases per biopsied embryo and surviving rate after biopsy. In human embryos, biopsy of diploid embryos produced 46.6% chromosome preparations, while 29% were obtained after blastomere disaggregation and 20.4% when biopsying triploid embryos. CONCLUSIONS: These results suggest that the disaggregating procedure and triploid embryos cannot be considered as good models to assess the feasibility of cytogenetic analysis in preimplantation diagnosis. Poor chromosome quality and loss during fixation are the main problems to use cytogenetics in preimplantation diagnosis; a combination of cytogenetics and other techniques is suggested in cases of balanced translocations. PMID- 7789580 TI - The psychological effects of multifetal pregnancy reduction. AB - OBJECTIVE: To study the psychological effects of multifetal pregnancy reduction. DESIGN AND SETTING: Hour-long semistructured telephone interviews with both multifetal pregnancy reduction patients and control subjects. PATIENTS: Forty-two multifetal pregnancy reduction patients were contacted within 1 year of undergoing the procedure. Forty-four control subjects had become pregnant after infertility evaluation or treatment but conceived only a single fetus or twins and thus did not consider fetal termination. MAIN OUTCOME MEASURES: Standardized measures of depressive disorder and current psychiatric symptoms, as well as questions about emotional reactions to multifetal pregnancy reduction. RESULTS: Reduction patients who were pregnant or postpartum at the time of the interview (n = 34) were no more likely than pregnant or postpartum controls (n = 34) to report episodes of depression or high psychiatric symptom levels. The same proportion (14.7%) of both reduction patients and controls with a successful pregnancy outcome met criteria for an episode of major depressive disorder occurring during the 9 months before the interview. In contrast, the 8 reduction patients who spontaneously aborted the entire pregnancy and the 10 controls who spontaneously aborted reported significantly higher rates of the full depressive syndrome. CONCLUSIONS: Multifetal pregnancy reduction is experienced as stressful and distressing. However, when pregnancy outcome is successful, the medical intervention does not put women at significant risk for affective illness or elevated levels of psychiatric symptoms. PMID- 7789581 TI - De novo formation of adhesions in endometriosis: the role of iron and free radical reactions. AB - OBJECTIVE: To show that raised iron levels in the peritoneal fluid (PF) of patients with endometriosis catalyze free radical reactions that results in the tissue destruction and fibrosis seen in these patients. DESIGN: A case-controlled study of the iron levels (microgram/mL) in the pelvic PF of 12 patients with moderate-to-severe disease, 15 patients with minimal-to-mild disease and in 17 women with normal pelvises were compared. As an index of free radical reactions through lipid peroxidation, the levels of malondialdehyde levels (ng/mL) were assessed simultaneously in the same specimens. RESULTS: Controlling for the phase of the menstrual cycle, significantly higher levels of iron were seen in patients with endometriosis, the levels being correlated with the severity of the disease. However no such corresponding relationship was seen in the malondialdehyde levels in the PF. CONCLUSIONS: These results suggest that raised iron levels in the PF do not play a role in catalyzing free radical reactions as judged by the degree of lipid peroxidation. PMID- 7789582 TI - Immunoreactive endothelin plasma levels in severe ovarian hyperstimulation syndrome. AB - OBJECTIVE: To determine the plasma levels of immunoreactive endothelin in patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study. SETTING: Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona, a tertiary care setting. PATIENTS: Sixteen IVF patients with severe OHSS. MAIN OUTCOME MEASURES: Measurement during the syndrome and 4 to 5 weeks after recovery of the following: mean arterial pressure, hematocrit, plasma renin activity, plasma aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic peptide, and immunoreactive endothelin concentrations. RESULTS: During the syndrome patients showed decreased mean arterial pressure (70.0 +/- 1.1 versus 85.2 +/- 1.6 mm Hg), increased mean hematocrit values (45.5% +/- 1.1% versus 38.1% +/- 0.4%), oliguria (630.6 +/- 40.7 versus 1,306.2 +/- 43.9 mL/d), and very high plasma levels of renin (36.0 +/ 9.1 versus 1.2 +/- 0.08 ng/mL per hour), aldosterone (190.6 +/- 28.4 versus 14.8 +/- 1.5 ng/dL), norepinephrine (602.1 +/- 91.0 versus 220.5 +/- 12.1 pg/mL), antidiuretic hormone (4.1 +/- 0.7 versus 1.0 +/- 0.1 pg/mL), and atrial natriuretic peptide (10.9 +/- 1.6 versus 4.7 +/- 0.2 fmol/mL). Immunoreactive endothelin plasma levels were increased significantly during OHSS (8.9 +/- 0.9 versus 3.9 +/- 0.2 pg/mL) and all patients had elevated values during the syndrome. CONCLUSIONS: Circulating plasma levels of immunoreactive endothelin are elevated in patients with severe OHSS in parallel with other neurohormonal vasoconstrictor systems. It may represent a homeostatic response to maintain blood pressure. PMID- 7789585 TI - Cumulative number and morphological score of embryos resulting in success: realistic expectations from in vitro fertilization-embryo transfer. AB - OBJECTIVE: To define statistical thresholds for the number and morphological score of embryos transferred that would be predictive of reproductive success in an IVF program. DESIGN: A retrospective review of patient records. SETTING: The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS: One hundred women who underwent IVF-ET for a diagnosis of tubal occlusion and later delivered viable infants. RESULTS: The mean number of embryos transferred before achieving live birth was 10.7 +/- 7.9 (mean +/- SD), with one half of patients achieving success within the first seven embryos transferred, and 95% achieving success within 25 embryos. For high quality embryos, the numbers were 7.5 +/- 6.3, 5, and 17, respectively, and, for the cumulative embryo score, a measure of both embryo morphology and metabolic activity, were 114.2 +/- 86.0, 83, and 280, respectively. Greater than 50% of live births occurred within the first two ET attempts. CONCLUSIONS: Although more than half of patients achieved reproductive success within the first two ETs and the first five high quality embryos transferred, after this threshold, fecundity declined rapidly. The calculation of cumulative embryo scores offered additional prognostic information. While all prior attempts to define IVF-ET failure have done so by including patients who did not become pregnant, we have found an analysis of our successes to be a useful adjunct in counseling patients. PMID- 7789583 TI - Modifications in uterine and intraovarian artery impedance in cycles of treatment with exogenous gonadotropins: effects of luteal phase support. AB - OBJECTIVE: To determine the effects of induction of multiple ovulation and of luteal P supplementation on the impedance to blood flow in the uterine and intraovarian arteries during the luteal phase. DESIGN: A prospective study using transvaginal color flow Doppler imaging. SETTING: A university-based infertility center. PATIENTS: Fifty-six women with unexplained or male factor-related infertility undergoing IUI. INTERVENTIONS: The patients were studied either during spontaneous cycles (n = 16) or in cycles of induction of multiple follicular development with purified FSH (n = 40). In 18 treated cycles, the luteal phase was supplemented with natural P. MAIN OUTCOME MEASURES: The pulsatility index was recorded from uterine and intraovarian arteries on the day of E2 peak and 5 and 10 days thereafter. On the same days, E2 and P plasma levels were measured by RIA. RESULTS: The intraovarian pulsatility index was significantly lower in FSH-treated than in spontaneous cycles on the day of E2 peak. Also, the uterine pulsatility index was significantly lower in treated cycles than in spontaneous cycles on the day of E2 peak and 5 days thereafter. In the late luteal phase, P supplementation was correlated with a significant decrease in uterine pulsatility index as compared with both spontaneous cycles and FSH-treated cycles without luteal support. CONCLUSIONS: Multiple follicular development is associated with a significant reduction in the impedance to perifollicular blood flow. Progesterone, as well as E2, seems able to decrease the impedance to blood flow in uterine arteries in women. PMID- 7789584 TI - Regulation of 72-kd type IV collagenase-matrix metalloproteinase-2 by estradiol and gonadotropin-releasing hormone agonist in human granulosa-lutein cells. AB - OBJECTIVE: To examine the hormonal regulation of 72-kd type IV collagenase gelatinase-matrix metalloproteinase-2 in human granulosa-lutein cells. DESIGN: The effect of E2 and GnRH agonist (GnRH-a) on matrix metalloproteinase-2 amount was examined on a long-term granulosa-lutein cell cultures. PATIENTS: The preovulatory follicles from women participating in our IVF program were aspirated through the vaginal wall. Follicular fluids were centrifuged and the granulosa cells were separated and pooled for culturing. MAIN OUTCOME MEASURES: Matrix metalloproteinase-2 enzyme activity was assayed with type IV collagen degradation assay and zymography. The matrix metalloproteinase-2 immunoreactive protein was studied by using specific antibodies. RESULTS: Matrix metalloproteinase-2 was the predominant form of gelatinase in cultured granulosa-lutein cells. The enzyme activity as well as the immunoreactive protein increased in the culture medium of the granulosa-lutein cells in the presence of E2. The effect of E2 was abolished by GnRH-a. CONCLUSIONS: Estradiol regulates the matrix metalloproteinase-2 enzyme amount in granulosa-lutein cells; the effect may be antagonized by GnRH-a. PMID- 7789586 TI - The results of in vitro fertilization-embryo transfer in couples with unexplained infertility failing to conceive with superovulation and intrauterine insemination. AB - OBJECTIVE: To determine the results of IVF-ET in couples with long-standing unexplained infertility who had failed to conceive with four to six cycles of superovulation and IUI. DESIGN: Retrospective case control series. SETTING: University IVF-ET center. PATIENTS: One hundred seventeen couples with unexplained infertility who had failed to conceive with superovulation and IUI underwent 157 cycles of IVF-ET. Results were compared with 194 tubal factor couples subjected to 250 IVF-ET cycles within the same time period. RESULTS: Total fertilization failure events were more common (20.4% versus 7.6%) and tended to be repetitive in couples with unexplained infertility. When total fertilization failure events were excluded, fertilization rates (57.8% versus 60.9%) and cumulative clinical pregnancy rates over three cycles (55.4% versus 46.5%) were similar in unexplained infertility and tubal disease groups. CONCLUSIONS: Couples with unexplained infertility failing to conceive with superovulation and IUI have a favorable outcome when treated subsequently with IVF-ET. Conception rates similar to couples with tubal disease may be expected despite a higher incidence of total fertilization failure events. PMID- 7789587 TI - The pregnancy rates of cohorts of idiopathic infertility couples gives insights into the underlying mechanism of infertility. AB - OBJECTIVES: To determine causes of "idiopathic" infertility, the IVF-ET experience of three cohorts of couples with this diagnosis was examined. DESIGN: Three cohorts of idiopathic infertility couples undergoing IVF-ET: a "failed IUI" group, three previous controlled ovarian hyperstimulation (COH)-IUI cycles with no pregnancies; a "conversion" group, patients converted during a COH-IUI cycle to IVF-ET because of excess follicle numbers; and a "direct IVF" group, patients proceeding directly to IVF-ET were compared. SETTING: A tertiary referral reproductive medicine unit. PARTICIPANTS: Forty-one idiopathic infertility couples. INTERVENTION: In vitro fertilization-ET. MAIN OUTCOME MEASURES: Number of oocytes retrieved, percent oocytes fertilized, number embryos per ET, implantation rate, percent pregnancy per cycle. RESULTS: The cohorts had similar fertilization rates and mean (+/- SD) number of pre-embryos transferred. The conversion group demonstrated a higher pregnancy rate (PR) per cycle and a higher E2 concentration than the other groups. The PR of 35.0% in the direct IVF group appeared higher than the 16.7% rate observed in the failed IUI group. CONCLUSIONS: Our observation of a lower PR in couples in the failed IUI group (16.7%) than in couples in the direct IVF group (35.0%) suggests pre-embryo developmental problems or implantation problems as likely important etiologies for a large proportion of idiopathic infertility couples. However, as the conversion group demonstrated both a significantly higher E2 concentration ([E2]) and per cycle PR than the other cohorts with similar fertilization and pre-embryo transfer rates. Subjects converted in a COH-IUI cycle to IVF-ET are thus either more likely to produce pre-embryos more genetically capable of continued development to implantation stage (i.e., better oocytes recruited and fertilized) or due to the higher [E2] to have endometrium more receptive to implantation. Neither undiagnosed tubal factors nor fertilization problems appear to be major etiologic contributors. PMID- 7789588 TI - Endometriosis, 1995--confusion or sense? AB - OBJECTIVE: To review current understanding of endometriosis. METHOD: A review of etiology, pathogenesis, relationship with infertility, medical and surgical treatment. RESULTS: It is likely that endometriosis occurs in most women at some stage in their reproductive years. Exposure to menstruation and estrogen are important etiologically. Current evidence suggests that implantation of menstrual endometrium is the commonest mechanism of pathogenesis. Clinical symptoms and signs are important in the diagnosis while laparoscopy remains the prime diagnostic technique. Treatment is not indicated for infertility but is for symptoms. Danazol and progestogens represent the best first-line therapy although gonadotropin-releasing hormone agonists are appropriate if economically justifiable. Both open and laparoscopic surgery are important especially in reconstructive work. The value of laser ablation in the treatment of infertility is unknown but it is effective in pain. The disease should be regarded as a recurrent problem and treatment strategies designed appropriately. CONCLUSION: Endometriosis still represents an intellectual and therapeutic challenge but successful treatment is possible especially if it is individualized for each patient. PMID- 7789591 TI - Antepartum vibroacoustic stimulation in patients with low fetal heart rate variability. AB - OBJECTIVE: The purpose of this study was to examine the effect of vibroacoustic stimulation during low fetal heart rate (FHR) variability. METHODS: FHR was analyzed 30 min before and 30 min after computerized vibroacoustic stimulation using the Oxford Sonicaid system 8000. The study comprised 32 healthy pregnant women with low antepartum FHR variability. The significance of difference of the median values was examined using Wilcoxon's matched-pairs signed-ranks test. RESULTS: Vibroacoustic stimulation of the fetus during low FHR variability evoked a significant increase in the number of accelerations (> 10 bpm) and an increase in long- and short-term variation. CONCLUSION: Our findings indicate that vibroacoustic stimulation during low FHR variability produces an abrupt change from a quiet to an active fetal state. PMID- 7789592 TI - Sonographically detected abnormalities of the umbilical cord. AB - OBJECTIVES: This study was undertaken as a retrospective chart review to evaluate the range of umbilical cord abnormalities detected by prenatal sonography, as well as the outcome and pathologic correlation. METHODS: We identified 13 cases of umbilical cord abnormalities detected sonographically over a 46-month period. We evaluated the ultrasound appearance, size, location, and color Doppler characteristic in each case. RESULTS: There were 4 instances of clear cysts on the umbilical cord, 8 with complex masses, and 1 with complete, cystic encasement of the cord throughout its length. The pathology included vascular abnormalities (hemangioma, hematoma, varicosity), edema of the umbilical cord with pseudocysts, and syncytial knots. There was 1 known karyotypic abnormality (trisomy 13). Twelve of the 13 newborns survived; the neonatal death occurred in the fetus with trisomy 13. CONCLUSION: The presence of umbilical cord abnormalities may represent a variety of pathologic entities. Clinical outcome is usually favorable. PMID- 7789589 TI - Stroke and pregnancy. AB - OBJECTIVE: To study the controversial relationship between pregnancy and stroke. Old studies and those from developing countries suggest that pregnancy considerably increases the risk of stroke. METHODS: The records of 946 consecutive cases of stroke observed in Saudi patients in 10 years were reviewed. Cases which occurred during pregnancy or during the first 15 days postpartum were included in the study. RESULTS: Twelve patients (1.3%) were pregnant or in postpartum at stroke onset. They constituted 27% of women of childbearing age. Cerebral infarction was diagnosed in nine cases and cerebral hemorrhage in three. Four patients died. CONCLUSION: The risk of stroke is only marginally increased (x 1.5) in pregnant compared with non-pregnant Saudi women. Many factors including peripartum cardiomyopathy, patent foramen ovale, changes in clotting factors, peripartum angiopathy and vasoactive steroid hormones, could be responsible for this increased risk. PMID- 7789593 TI - A clinical, mammographic, sonographic and histologic evaluation of breast cancer. AB - OBJECTIVE: To evaluate histologic tumor size in comparison with preoperative determination of tumor diameter by palpation, mammography and sonography. METHODS: In a retrospective analysis we compared the histologic, clinical, mammographic and sonographic findings obtained from 160 patients with breast carcinoma. RESULTS: The histologically determined tumors showed an average diameter of 25.7 mm. By comparison, the average tumor diameter determined by mammography, sonography and palpation was 23.8, 26.1 and 30.6 mm, respectively. Mammography was capable of detecting 94.5% of breast carcinomas, breast sonography 91% and palpation 87%. The combinations of mammography and sonography or mammography and palpation detected 99% of carcinomas, and sonography and palpation 95% of carcinomas. CONCLUSION: As supplementary methods to preoperative clinical examination, mammography and breast sonography are mutually complementary, high-resolution imaging techniques of utmost importance in the preoperative diagnosis and surgical treatment of breast cancer patients. PMID- 7789594 TI - Ruptured intracranial aneurysm complicating pregnancy. AB - Three cases of ruptured intracranial aneurysm during pregnancy are presented. Rupture occurred near term in all three cases. Simultaneous elective cesarean section and clipping of the aneurysm was performed in two cases. Successful maternal and perinatal outcome was achieved in all three patients. The diagnosis and management of the cases are described and discussed. PMID- 7789590 TI - Induction of labor utilizing vaginal vs. intracervical prostaglandin E2. AB - OBJECTIVE: To compare the efficacy of intracervical vs. vaginal prostaglandin E2 (PGE2) gel for induction of labor. METHOD: Sixty-eight women scheduled for elective induction of labor at term were randomized to receive either 0.5 mg intracervical PGE2 (I/C group, n = 37) or 2 mg vaginal PGE2 gel (Vag group, n = 31) on a 6-hourly basis for a maximum of three doses. RESULTS: Three participants who delivered by cesarean section soon after gel administration were excluded from further analysis. Twenty-nine of 30 (97%) in the Vag group were successfully induced compared with 23 of 35 (66%) in the I/C group (P < 0.01). The induction active labor intervals were 8.0 +/- 5.4 h for the Vag group and 23.1 +/- 27.6 h for the I/C group (P = 0.002). The induction-delivery intervals were 12.4 +/- 6.3 h for the Vag group and 29.8 +/- 29.1 h for the I/C group (P = 0.001). Uterine hyperstimulation and perinatal outcome were similar in both groups. CONCLUSION: Vaginal PGE2 was more efficacious than intracervical PGE2 in inducing labor. PMID- 7789595 TI - Aggressive angiomyxoma of the vagina. AB - Aggressive angiomyxoma is a recently described pathological condition which affects mainly the soft tissues of the pelvis and perineum in women. It is neither encapsulated nor circumscribed and has a tendency for local recurrence. We report a 50-year-old woman who presented with a mass arising within the vaginal wall and extending to the perineum which appeared cystic on ultrasound. The mass was excised and there is no evidence of recurrence 40 months after surgery. PMID- 7789596 TI - The unfavorable cervix: improving the Bishop score using the Foley catheter. PMID- 7789598 TI - Hydatidiform mole co-existing with a normal fetus. PMID- 7789597 TI - Magnesium toxicity and resuscitation--an unusual cause of postcesarean evisceration. PMID- 7789599 TI - Endometriosis causing very high early first trimester serum CA 125 levels. PMID- 7789600 TI - Administration of heparin inhalations for correction of blood antithrombin activity in pregnant women with IDDM. PMID- 7789601 TI - GnRHa and steroid add-back therapy for uterine myoma. PMID- 7789602 TI - Tuberculosis of Bartholin's gland. PMID- 7789603 TI - Chondrosarcoma: an uncommon pelvic mass. PMID- 7789604 TI - Bowen's disease and Bowenoid papulosis of the vulva. PMID- 7789605 TI - Perforation of the uterus and colon by copper-T intrauterine contraceptive device. PMID- 7789606 TI - ACOG technical bulletin. Blood component therapy. Number 199--November 1994 (replaces no. 78, July 1984). Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists. AB - Component therapy is the standard method for most transfusion needs and has made the use of whole blood rarely necessary. By giving only the specific component that is needed, blood component therapy usually provides better treatment. Because blood and blood products are in short supply and most carry some risk of infection, the National Institutes of Health guidelines for the use of each component should be followed closely. When significant blood loss is anticipated, autologous predonation should be considered and discussed with the patient. PMID- 7789608 TI - ACOG committee opinion. Laparoscopically assisted vaginal hysterectomy. Number 146--November 1994. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. PMID- 7789607 TI - ACOG committee opinion. Sexual misconduct in the practice of obstetrics and gynecology: ethical considerations. Number 144--November 1994. Committee on Ethics. American College of Obstetricians and Gynecologists. PMID- 7789610 TI - Blocking K+ channels with TEA induces plasmalemma depolarization, increased [Ca2+]i, and ACTH secretion in AtT-20 cells. AB - Blocking K+ channels induces hormone secretion in various pituitary cell lines by a mechanism which is not completely delineated. In the present study, we employed the mouse pituitary tumor-derived AtT-20 cell as a model to evaluate this phenomenon. We correlated the effect of the K+ channel-blocker, tetraethylammonium (TEA), on K+ current and membrane potential utilizing whole cell recording, on cytosol Ca2+ ([Ca2+]i) concentration utilizing fura-2, and on ACTH secretion utilizing a perifusion system. TEA inhibited voltage-dependent K+ current and initiated membrane depolarization in a dose-dependent fashion. Divergences in the sensitivity to TEA between voltage-dependent K+ currents and membrane depolarization indicate that voltage-dependent K+ channels are not responsible for TEA-induced depolarization TEA (1-30 mM) also induced a concentration-dependent rise in [Ca2+]i concentration and ACTH secretion, both of which were inhibited by removing medium Ca2+. Our data indicate that TEA inhibits K+ currents and induces membrane depolarization; this opens Ca2+ channels in the plasmalemma, causing a rise in [Ca2+]i which initiates ACTH secretion. Alteration of K+ channel permeability by hormones or neurotransmitters may thus play an important regulatory role in controlling pituitary hormone secretion. PMID- 7789609 TI - Quantitative differences in androgen and glucocorticoid receptor DNA binding properties contribute to receptor-selective transcriptional regulation. AB - Androgen receptor (AR) and glucocorticoid receptor (GR) belong to the same subfamily of steroid/nuclear receptors and have been shown to bind qualitatively to the same hormone response element (HRE) DNA sequences. Despite this similarity in target gene recognition, AR and GR have differential affects on the transcriptional regulation of genes containing both simple and complex HRE control regions. Using HREs from the mouse mammary tumor virus (MMTV), tyrosine aminotransferase (TAT), prostatein (C3) or sex-limited protein (SLP) genes, linked to the thymidine kinase promoter, we found receptor-selective differences in the ability of rat AR and rat GR to induce transcription of these various reporter genes. Since AR and GR have a 20% amino acid sequence difference in their DNA binding domains (DBDs), which could result in altered DNA binding affinities, we measured the ability of purified AR and GR DBDs to bind selectively and with high affinity to these HRE sequences in vitro. Gel shift mobility assays showed that the GR DBD had a higher affinity for a consensus HRE than did the AR DBD, and quantitative DNase I footprinting revealed that AR and GR DBDs bound to the MMTV, TAT, C3 and SLP HREs with different affinities. It was found that AR had a dissociation constant (Kd) that was 2-3 times higher than GR on the TAT, C3 and SLP HREs and that the Kd of AR for the C3 and SLP HREs differed by an order of magnitude (43 nM and 460 nM, respectively). Taken together, these data suggest that amino acid differences in the AR and GR DBDs contribute to altered receptor-DNA interactions, however it is likely that non receptor factors are involved in further modulating receptor-selective DNA binding and transactivation functions. PMID- 7789611 TI - The antioxidant beta-carotene prevents covalent cross-linking between cholesterol side-chain cleavage cytochrome P450 and its electron donor, adrenodoxin, in bovine luteal cells. AB - Steroid hormones are an important class of hormones synthesized from cholesterol by a number of endocrine organs; including ovaries, placenta, testes and adrenal glands. The first and rate-limiting step in steroidogenesis is the cleavage of the side-chain of the cholesterol molecule, catalysed by a cytochrome P450 enzyme, cholesterol side-chain cleavage enzyme. This enzyme, as with other P450 enzymes, produces oxygen radicals. Oxygen free radicals can cause deleterious effects such as cross-linking and aggregation of proteins. Cells can protect against such damage with the use of antioxidants. The corpus luteum, or 'yellow body', of the ovary is very steroidogenic and is exceedingly rich in the yellow antioxidant, beta-carotene. The corpus luteum produces the steroid hormone progesterone that is needed to support pregnancy. Here we have shown that by depleting, or conversely repleting, luteal cells of their beta-carotene content in vitro that P450 side-chain cleavage enzyme became covalently non-disulfide cross-linked to its electron donor, adrenodoxin, and hence inactivated. Bovine luteal cells were cultured in 10% fetal calf serum with or without additional treatments for up to 72 h. Under control conditions the cellular levels of beta carotene and alpha-tocopherol fell by 50% within 24 h and remained low. P450 side chain cleavage enzyme become non-disulfide covalently cross-linked to its electron donor, adrenodoxin, as determined by Western immunoblotting (N = 18). Aminoglutethamide inhibited this cross-linking. The addition of beta-carotene at levels found in bovine serum, but not alpha-tocopherol or ascorbic acid, inhibited the degree of the cross-linking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789612 TI - Human placental endothelin: expression of endothelin-1 mRNA by human placental fibroblasts in culture. AB - Endothelin-1 (ET-1) mRNA is expressed by the human placenta in a developmentally regulated manner and has been shown to stimulate the growth of placental mesenchymal cells. The ability of placental fibroblasts to express preproET-1 mRNA was studied to determine if ET-1 could potentially participate via autocrine mechanisms in the proliferation of placental fibroblasts. Fibroblasts were isolated from normal placentae at various gestational ages (7-19 weeks and term) and their abilities to express preproET-1 mRNA in culture evaluated by Northern analysis. Sparse, rapidly growing cultures of placental fibroblasts expressed preproET-1 mRNA at each gestational age in the presence of 10% FBS. The regulation of preproET-1 expression in placental fibroblasts was studied by exposing cells to known mitogenic stimuli. Quiescent, confluent monolayers of placental fibroblasts expressed no detectable levels of preproET-1 mRNA under basal conditions. Epidermal growth factor (EGF, 10 mg/ml), transforming growth factor-beta 1 (TGF-beta 1, 5 ng/ml), or interleukin 1 beta (IL-1 beta) alone, had no significant effect on steady state preproET-1 mRNA levels. Cycloheximide, an inhibitor of protein synthesis, increased the steady state levels of preproET-1 mRNA at a concentration of 10 micrograms/ml. In the presence cycloheximide, IL-1 beta markedly stimulated preproET-1 mRNA expression, whereas EGF was less effective. TGF-beta 1 had no effect in the presence or absence of cycloheximide. In contrast, 12-O-tetradecanoylphorbol 13-acetate (TPA, 20 nM) exerted a small stimulatory effect on preproET-1 mRNA expression which was not influenced by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789613 TI - Immunochemical and flow cytometric analysis of androgen receptor expression in thymocytes. AB - A variety of evidence suggests that the cells of the immune system are targets for the actions of gonadal steroids. Experiments in both normal animals and in autoimmune disease models have established that androgens exert immunomodulatory effects at the level of the thymus. We have attempted to define precisely the potential target cells for androgen action in the thymus using recently developed antibodies to the androgen receptor. We report here that these antibodies reveal AR expression in all classes of thymocytes defined by surface markers CD4 and CD8. The highest levels of AR expression were observed in the CD4-CD8+ and CD4 CD8- subsets that include the most immature cells. These experiments establish that thymocytes are potential targets for direct actions of androgens. The data further suggest AR expression in thymocytes may be developmentally regulated in these cells, and that androgen effects early in the process of thymocyte selection may contribute to the sexual dimorphism of immune responsiveness. PMID- 7789614 TI - Rainbow trout estrogen receptor presents an equal specificity but a differential sensitivity for estrogens than human estrogen receptor. AB - The estrogen receptor is a transcription factor that mediates the actions of estrogens which plays a major role in salmonid vitellogenesis. Previously, we cloned and described the estradiol receptor in rainbow trout. To study the transactivation characteristics, the full length cDNA was inserted in an expression vector and tested by transfection on an estrogen-dependent promoter (pERE-TK-CAT). For the first time, direct comparison between the trout receptor (rtER) and human receptor (hER) in an analogous system has been possible. We demonstrate that rtER can, like hER, transactivate transcription in a strictly hormone-dependent manner. The specificity and sensitivity of the rtER response to different steroids have been studied. With rtER, the E2 concentration needed for half maximal activation is 10 times higher than with hER. In addition, we show that rtER has a weak affinity for androgens and transactivation could be induced using high testosterone concentration. Experiments show that both rtER and hER have an equal specificity for estrogens but that the rtER binds its ligand with a lower sensitivity than hER. Several hypotheses concerning the role of main amino acids within the receptor protein are proposed based on the different properties of the receptors and comparison of sequences. PMID- 7789615 TI - In situ gene expression of growth hormone (GH) receptor and GH binding protein in adult male rat tissues. AB - Pituitary growth hormone (GH) acts as a growth promoter in a wide range of tissues after binding to its specific GH receptor (GHR) or to a cytosolic circulating GH binding protein (GHBP). To further characterize GH target cells in the rat, in situ hybridization was used to investigate the tissue and cell distribution of mRNAs encoding GHR and GHBP, and their hepatic developmental expression was examined. Cryostat sections of adult male rat tissue were hybridized with [35S]dATP-labeled oligonucleotide antisense probes, one directed against a specific sequence of the intracellular domain of rat GHR mRNA, the other against the hydrophilic tail of rat GHBP mRNA. Several tests were carried out to validate the in situ detection of mRNA. Co-expression of the two transcripts in liver, spleen, thymus, kidney, adrenal, skin, muscle, heart, and pituitary was autoradiographically detected. However, relative expression levels, as demonstrated by computer-assisted microdensitometry, appeared to be variable. Both transcripts showed higher levels of expression in the liver, anterior and intermediate pituitary lobes, outer kidney medulla, adrenal cortex, skin epidermis, heart and muscle, but lower levels in spleen, thymus, hypodermis, adrenal medulla and posterior pituitary lobe. As a physiological control, hepatic levels of expression were examined during development, and the two forms of mRNA were found to be present at low levels in fetal liver, increasing considerably after birth. These results permit the identification in the adult male rat of cells that might be directly responsive to GH, and demonstrate the differential expression of rGHR and rGHBP transcripts. PMID- 7789616 TI - Dexamethasone recruits atrial natriuretic peptide secretory cells in the rat left atrium and apex of the ventricle. AB - The response of the atrial natriuretic peptide (ANP) secreting cells from both rat atria and the apex of the ventricles to dexamethasone (DEX) was analyzed by the plaque assay. In right atrial cardiocytes, 25% of the cells secreted ANP basally; DEX treatment did not alter this percentage. However, in the left atrial secretory population, a discordance between the basal (15%) and DEX stimulated (25%) percent plaque formation was found. ANP secreting cells from the ventricular apex responded similarly to DEX exposure (26%), with 8% of the cells basally releasing the hormone. These data suggest that in both the left atria and apex of the rat ventricles, exposure to DEX recruits ANP secretory cells from a non-secreting population. Consequently, the release of ANP from these tissues would increase after glucocorticoid stimulation. PMID- 7789617 TI - Effect of tyrosine kinase inhibitors on luteinizing hormone-releasing hormone (LHRH)-induced gonadotropin release from the anterior pituitary. AB - A range of selective tyrosine kinase inhibitors, piceatannol, methyl-2,5 dihydroxycinnamate (MDC), genistein, psi-tectorigenin and lavendustin A, all reduced luteinizing hormone-releasing hormone (LHRH)-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from pro-oestrous rat hemipituitaries incubated in vitro. In general, both 'initial' release and the augmented release resulting from LHRH self-priming, were reduced in parallel in a concentration-dependent fashion. The effects of piceatannol were independent of the steroidal status of the pituitary tissue. Both piceatannol and MDC greatly reduced LH release by ionomycin and a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), suggesting that the tyrosine kinase(s)-dependent step is in the later stages of the stimulus-secretion pathway activated by the LHRH receptor. These data were supported by immunoblots for phosphotyrosine showing that in the gonadotrope-derived alpha T3-1 cell line, treatment with LHRH caused piceatannol-sensitive increases in specific tyrosine phosphorylation of several proteins (major bands at 65-75 and 120-130 kDa). Treatment of cells with PDBu mimicked the tyrosine phosphorylations evoked by LHRH whereas the PKC inhibitor, GF109203X, partially reduced both LHRH- and PDBu-induced tyrosine phosphorylations. Direct effects of MDC and piceatannol on PKC were assessed in an in vitro PKC assay; piceatannol, but not MDC, inhibited PKC activity but at considerably higher concentrations than required for inhibition of LHRH-induced gonadotropin secretion. These data support a role for tyrosine kinase activation in LHRH-induced secretion. PMID- 7789618 TI - Retinoic acid receptor alpha 1 isoform is induced by estradiol and confers retinoic acid sensitivity in human breast cancer cells. AB - Retinoic acid (RA) inhibits proliferation of estrogen receptor (ER)-positive human breast cancer cells, but not the growth of ER-negative cells. We have shown previously that ER-positive cells express higher levels of retinoic acid receptor (RAR) alpha, suggesting that RAR alpha gene expression may be regulated in breast cancer cells by estrogens. We here report that estradiol (E2) increases RAR alpha mRNA in a time- and concentration-dependent manner resulting in a marked increase in RAR alpha protein expression, and present evidence that RAR alpha 1 is the only known isoform of RAR alpha regulated by E2 in breast cancer cells. In parallel we demonstrate that ER-positive cells exhibit greater RA sensitivity in the presence of E2, suggesting that E2-induced expression of RAR alpha 1 is involved in growth inhibition by RA. To directly investigate the role of RAR alpha 1 in RA-mediated growth inhibition, we introduced RAR alpha 1 expression vectors into RA-resistant and ER-negative MDA-MB-231 cells. The RAR alpha 1 transfected cells were growth inhibited by RA, while mock- and untransfected cells were unresponsive. Together, our data indicate that adequate levels of RAR alpha 1, either generated by introduction of expression vectors or endogenously induced by estrogens, are required for growth inhibition of breast cancer cells by RA. PMID- 7789619 TI - Possible sites of dopaminergic inhibition of gonadotropin release from the pituitary of a teleost fish, tilapia. AB - The present study is an attempt to find sites of dopaminergic inhibition along the transduction cascades culminating in gonadotropin (GtH) release in a teleost fish, tilapia. Experiments were carried out on perifused pituitary fragments and in primary culture of trypsinized pituitary cells. Salmon GnRH, chicken GnRH I and II stimulated GtH release in culture with estimated ED50 values of 15.56 pM, 2.55 nM and 8.65 pM, respectively. Apomorphine (APO; 1 microM) totally abolished this stimulation. Dopamine (DA; 1 microM) reduced both basal and GnRHa-stimulated GtH release from perifused pituitary fragments but did not alter the formation of cAMP. In a similar perifusion experiment DA abolished GtH release in response to forskolin (10 microM) with no reduction in cAMP formation. This indicates that one site of the dopaminergic inhibition is distal to cAMP formation, an indication not compatible with the classic characteristic of DA D2 type mode of action. The inhibition of GtH release in culture, caused by 1 microM APO, the specific DA D2 agonists LY 171555 (LY) or bromocryptine (BRCR) could not be reversed by activating protein kinase C (PKC) by DiC8 or the phorbol ester TPA. This would indicate a site for DA action distal to PKC. However, the stimulatory effect of arachidonic acid (AA; 50 microM) in perifusion was not reduced by DA (1 microM) or by APO, LY or BRCR in culture, which suggests a site for DA action proximal to AA formation. APO, LY and BRCR reduced GtH release in response to the Ca2+ ionophore A23187, however, their inhibitory effect was reversed by 10 microM ionomycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789620 TI - Regulation of steroidogenesis in crayfish molting glands: involvement of protein synthesis. AB - The involvement of continuous protein synthesis in the mechanisms of crustacean steroidogenesis was investigated using crayfish molting glands (Y-organs). During intermolt, Y-organ steroidogenic activity is low. Eyestalk ablation initiates premolt which is characterized by a rapid increase in the production of ecdysteroids. In vitro incorporation of [14C]leucine into TCA-precipitable proteins was measured in Y-organs. A significant increase of de novo protein synthesis within 2 h and simultaneously led to a strong inhibition of the ecdysteroid synthesis. Sinus gland extracts (containing molt inhibiting hormone) also induced both a limited but reproducible inhibition of Y-organ protein synthesis and a pronounced inhibition of ecdysteroid production within 2 h. The results suggest a functional link between protein synthesis in the Y-organ and sustained ecdysteroid production. The analysis of autoradiographs from one dimensional gel electrophoreses revealed an overall increase in de novo synthesis of glandular proteins in early premolt but also a more specific effect on distinct proteins (increase of 150, 140, 50-60, 22 and 15-18 kDa proteins) which may be more directly involved in the regulation of ecdysteroidogenesis. PMID- 7789621 TI - Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy. AB - Several mechanisms are implicated in the pathogenesis of diabetic retinopathy. They include biochemical, hemodynamic, and hormonal factors, all of which have an important role in the development of diabetic retinopathy. These factors are not independent of each other, but rather they interact and together are responsible for the well-known lesions of vascular occlusion, microaneurysms, hemorrhages' hard exudates, and eventually new vessel formation. PMID- 7789622 TI - HLA-DQB1*0602 is associated with dominant protection from diabetes even among islet cell antibody-positive first-degree relatives of patients with IDDM. AB - HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). We investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody positive (ICA+) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives. We human leukocyte antigen-typed and periodically tested beta-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 ICA+ relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201. The frequency of DQB1*0302 and DQB1*0201 and of the high-risk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype. However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02). We found DQB1*0602 in 8 of 72 (11.1%) ICA+ relatives. Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602- relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA+ relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials. PMID- 7789623 TI - Genetic linkage of thymic T-cell proliferative unresponsiveness to mouse chromosome 11 in NOD mice. A possible role for chemokine genes. AB - Thymic and peripheral T-cells from NOD mice display a proliferative unresponsiveness on stimulation through the T-cell receptor/CD3 complex. Interleukin 4 reverses NOD T-cell unresponsiveness in vitro and prevents the onset of diabetes in vivo, suggesting a causal relationship between the T-cell unresponsiveness and diabetes susceptibility in NOD mice. Both quantitative trait loci analysis of BXD recombinant inbred mice and linkage analysis of NOD outcross populations reveal that the control of NOD thymic T-cell proliferative unresponsiveness genetically maps to a central region on mouse chromosome 11, which includes the beta-chemokine gene family. This finding raises the possibility that a beta-chemokine(s) may regulate T-cell unresponsiveness as well as diabetes susceptibility in NOD mice. PMID- 7789624 TI - Insulin gene region-encoded susceptibility to IDDM maps upstream of the insulin gene. AB - The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at -23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the -23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2. PMID- 7789625 TI - Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. AB - Effects of human glucagon-like peptide I (GLP-I)(7-36)amide were examined in volunteers having insulin-dependent diabetes mellitus (IDDM) with residual C peptide (CP) secretion (n = 8, 7 men and 1 woman; age, 31 +/- 1.4 years; body mass index, 24.7 +/- 0.7 kg/m2; duration of diabetes, 3.2 +/- 0.8 years; insulin dose, 0.41 +/- 0.05 U.kg-1.day-1; meal-stimulated CP, 1.0 +/- 0.2 nmol/l [means +/- SE]). After a mixed meal (Sustacal, 30 kJ/kg body wt), intravenous injection of GLP-I, 1.2 pmol.kg-1.min-1 through 120 min, virtually abolished increments of plasma glucose, CP, pancreatic polypeptide (PP), and glucagon concentrations, with no significant effect on plasma gastrin levels during the infusions. At reduced dosage (0.75 pmol.kg-1.min-1), GLP-I had lesser effects on plasma glucose and CP levels. On cessation of intravenous GLP-I infusions after the meals, plasma glucose, CP, PP, and glucagon concentrations rebounded toward control levels by 180 min, and the response of plasma gastrin was prolonged. These rebound responses are consistent with intestinal delivery of food retained in the stomach on escape from inhibition of gastric emptying by GLP-I. Infusion of 1.2 pmol.kg-1.min-1 GLP-I with 20 g glucose (10% dextrose in water) injected intravenously over 60 min enhanced plasma responses of immunoreactive CP; the mean incremental areas under concentration curves (0-60 min) increased sixfold, but the glycemic excursion was not affected. Thus, in CP-positive IDDM, pharmacological doses of GLP-I reduce glycemic excursions after meals by a mechanism(s) not dependent on stimulation of insulin secretion, presumably involving delayed gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789626 TI - Comparison of estimates of insulin sensitivity from minimal model analysis of the insulin-modified frequently sampled intravenous glucose tolerance test and the isoglycemic hyperinsulinemic clamp in subjects with NIDDM. AB - Minimal model (MINMOD) analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT) is dependent on an adequate insulin response to the glucose load. As this is characteristically deficient in subjects with non insulin-dependent diabetes mellitus (NIDDM), the technique has been modified by the use of an intravenous bolus of insulin. Previous validation of this modification in humans has relied on agreement between insulin sensitivity indexes (SI) estimated from tolbutamide- and insulin-modified tests and not on direct comparison with estimates derived from the isoglycemic glucose clamp. We have compared estimates of insulin sensitivity derived from minimal modeling of a 4-h insulin-modified FSIVGTT and the glucose clamp in subjects with NIDDM. Twelve subjects underwent an insulin-modified FSIVGTT and an isoglycemic hyperinsulinemic clamp in random order 2-4 weeks apart. Fasting plasma glucose (8.4 vs. 9.0 mmol/l) and immunoreactive insulin (IRI) concentrations (104.5 vs. 101.5 pmol/l) were not different between the 2 study days. SI(clamp) was derived from the steady-state glucose infusion rate during the 3rd h of the clamp, corrected for the ambient insulin and glucose concentrations. SI(ivgtt) was derived using MINMOD. SI(ivgtt) was 1.06 +/- 0.18 min-1.mU-1.ml x 10(4), and mean SI(clamp) was 4.97 +/- 0.69 l.min-1/pmol.l-1 x 10(4) (mean +/- SE). SI(ivgtt) was positively correlated with SI(clamp) (r = 0.73, P = 0.004) and negatively correlated with body mass index (r = -0.7, P = 0.005) and fasting IRI(ivgtt) (r = -0.64, P = 0.008). In summary, MINMOD analysis of the insulin-modified FSIVGTT provides a valid measure of insulin sensitivity in subjects with NIDDM. PMID- 7789627 TI - Disease sensitivity and specificity of 52 assays for glutamic acid decarboxylase antibodies. The Second International GADAB Workshop. AB - There is increasing interest in the use of glutamic acid decarboxylase antibodies (GADAbs) for identification of subjects at increased risk of developing insulin dependent diabetes mellitus (IDDM). However, considerable variation exists between laboratories in the reported frequency of GADAb in various clinical situations, and disease sensitivity and specificity have not yet been compared between assays. An international workshop was held in which 101 coded freeze dried sera, including 39 from subjects with newly diagnosed IDDM, 32 from healthy control subjects, 4 from nondiabetic subjects with Graves' disease, and 4 from islet cell antibody-positive subjects, were analyzed in 52 assays (radiobinding assay [RBA], 26; enzyme-linked immunosorbent assay [ELISA], 19; and enzymatic immunoprecipitation assay [EIP], 7). The mean sensitivity for RBAs (76.2%) was higher than for ELISAs (36.5%) and EIPs (49.9%) (P < 0.01). The mean specificity was similar for each assay format (RBA, 89.4%; ELISA. 89.4%; and EIP, 92.3%). The lower sensitivities of the ELISA and EIP were predominantly due to the inability of these assays to detect low levels of GADAb in IDDM. To convert results to standard units, standard curves were constructed using duplicate dilutions of the anti-glutamic acid decarboxylase monoclonal antibody MICA 3 and serum from a patient with stiff-man syndrome (SMS). Curves could be derived in 28 assays using the MICA 3 serum and in 29 using the SMS serum. The mean coefficients of variation between assays for disease and control samples were 45% when results were converted to MICA units, 77% for SMS units, and 76% for SD scores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789628 TI - Insulin-induced sympathetic activation and vasodilation in skeletal muscle. Effects of insulin resistance in lean subjects. AB - Insulin-induced stimulation of blood flow and sympathetic nerve activity in skeletal muscle tissue is impaired in obesity, but the underlying mechanism is unknown. To determine whether insulin resistance alters sympathetic and vasodilatory responses to euglycemic hyperinsulinemia, in eight healthy subjects we measured calf blood flow and muscle sympathetic nerve activity (MSNA) (n = 5) during insulin/glucose infusion (euglycemic hyperinsulinemic [6 pmol.kg-1.min-1] clamp) performed alone and performed during concomitant fat emulsion infusion, a maneuver designed to induce insulin resistance. The major new finding is that fat emulsion infusion, which attenuated insulin-induced stimulation of carbohydrate oxidation by 39 +/- 7% (P < 0.01), did not have any detectable effect on insulin induced vasodilatory and sympathetic responses: at the end of the 2-h clamp, blood flow and MSNA had increased by 35 +/- 6% (P < 0.01) and 152 +/- 58% (P < 0.01), respectively, during insulin infusion alone and by 35 +/- 7% (P < 0.01) and 244 +/- 90% (P < 0.01), respectively, during insulin infusion superimposed on free fatty acid infusion. These observations in lean healthy subjects indicate that induction of resistance to the stimulatory effects of insulin on carbohydrate metabolism does not attenuate muscle blood flow and MSNA responses evoked by acute euglycemic hyperinsulinemia. These findings provide further evidence that hyperinsulinemia per se is the primary stimulus that triggers stimulation of muscle blood flow and MSNA during insulin/glucose infusion in humans and suggest that the impaired insulin-induced vasodilation in obese subjects is not related primarily to impaired stimulation of muscle carbohydrate metabolism. PMID- 7789629 TI - Acute hyperglycemia provides an insulin-independent inducer for GLUT4 translocation in C2C12 myotubes and rat skeletal muscle. AB - GLUT4 translocation and activation of glucose uptake in skeletal muscle can be induced by both physiological (i.e., insulin, nerve stimulation, or exercise) and pharmacological (i.e., phorbol ester) means. Recently, we demonstrated that high glucose levels may mimic the effects of phorbol esters on protein kinase C (PKC) and insulin receptor function (J Biol Chem 269:3381-3386, 1994). In this study, we tested whether the previously described effects of phorbol esters on translocation of GLUT4 in myotubes in culture and also in rat skeletal muscle might be mimicked by glucose. We found that stimulation of C2C12 myotubes with both insulin (10(-7) mol/l, 5 min) and glucose (25 mmol/l, 10 min) induces a comparable increase of the GLUT4 content in the plasma membrane. To test whether this effect occurs in intact rat skeletal muscle as well, two different model systems were used. As an in vitro model, isolated rat hindlimbs were perfused for 80 min with medium containing 6 mmol/l glucose +/- insulin (1.6 x 10(-9) mmol/l, 40 min) or 25 mmol/l glucose. As an in vivo model, acute hyperglycemia (> 11 mmol/l glucose, 20 min) was induced in Wistar rats by intraperitoneal injection of glucose under simultaneous suppression of the endogenous insulin release by injection of somatostatin. In both models, subcellular fractions were prepared from hindlimb skeletal muscle, and plasma membranes were characterized by the enrichment of the marker enzyme alpha 1 Na(+)-K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789630 TI - A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group. AB - Coxsackievirus B infections have been associated with clinical manifestation of insulin-dependent diabetes mellitus (IDDM) in several studies, but their initiating role in the slowly progressing beta-cell damage is not known. This is the first prospective study designed to assess the role of coxsackie B and other enterovirus infections in the induction and acceleration of this process. Three separate series were studied: 1) an intrauterine exposure series comprising 96 pregnant mothers whose children subsequently manifested IDDM and 96 control mothers whose children remained nondiabetic; 2) a cohort of 22 initially unaffected siblings of diabetic children who were followed until they developed clinical IDDM (mean observation time, 29 months) and 110 control siblings who remained nondiabetic; 3) a case-control series comprising 90 children with newly diagnosed IDDM and 90 control subjects. Enterovirus infections were identified on the basis of significant increases in serum IgG, IgM, or IgA class antibodies against a panel of enterovirus antigens (capture radioimmunoassay). Enterovirus antibodies were significantly elevated in pregnant mothers whose children subsequently manifested IDDM, particularly in cases in which IDDM appeared at a very young age, before the age of 3 years (P < 0.005). Serologically verified enterovirus infections were almost two times more frequent in siblings who developed clinical IDDM than in siblings who remained nondiabetic (mean, 1.0 vs. 0.6 infections/follow-up year; P < 0.001). This difference was seen both close to the diagnosis of IDDM and several years before diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789631 TI - Effects of angiotensin-converting enzyme inhibitors, Ca2+ channel antagonists, and alpha-adrenergic blockers on glucose and lipid metabolism in NIDDM patients with hypertension. AB - We compared the effects of captopril, nifedipine, and doxazosin on glucose and lipid metabolism in 30 hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients (age = 50 +/- 3 years; body mass index = 30 +/- 1 kg/m2). Of these patients, 9 were treated with captopril, 11 with nifedipine, and 10 with doxazosin for 12 weeks. Blood pressure, fasting plasma glucose (FPG) concentration, HbA1c, oral glucose tolerance test (OGTT), euglycemic insulin clamp, and plasma lipids were measured before and after a 3-month period. Mean arterial blood pressure (114 +/- 2 mmHg) was similar in all groups before initiating antihypertensive therapy and declined to 102 +/- 2 (captopril), 103 +/ 1 (nifedipine), and 103 +/- 2 (doxazosin) mmHg (P < 0.001). Baseline FPG (148 +/ 11 mg/dl) and HbA1c (6.3 +/- 1%) were similar in all groups and did not change significantly with treatment. Plasma glucose, insulin, and free fatty acid (FFA) concentrations during the OGTT were similar in all groups before antihypertensive treatment and did not change with captopril and nifedipine; after doxazosin, plasma glucose and FFA concentrations during the OGTT decreased (both P < 0.05) without change in plasma insulin response. Insulin-mediated glucose uptake (144 +/- 11 mg.m-2.min-1), glucose oxidation (76 +/- 4 mg.m-2.min-1), and nonoxidative glucose disposal (71 +/- 6 mg.m-2.min-1) were similar in all groups before the start of antihypertensive treatment and did not change in captopril and nifedipine groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789633 TI - Okadaic acid, vanadate, and phenylarsine oxide stimulate 2-deoxyglucose transport in insulin-resistant human skeletal muscle. AB - In response to insulin, several proteins are phosphorylated on tyrosine and on serine/threonine residues. Decreased phosphorylation of signaling peptides by a defective insulin receptor kinase may be a cause of insulin resistance. Accordingly, inhibition of the appropriate phosphatases might increase the phosphorylation state of these signaling peptides and thereby elicit increased glucose transport. The purpose of this study was to examine the effect of the serine/threonine phosphatase inhibitor okadaic acid and the tyrosine phosphatase inhibitors phenylarsine oxide and vanadate on 2-deoxyglucose transport in insulin resistant human skeletal muscle. All three phosphatase inhibitors stimulated 2 deoxyglucose transport in insulin-resistant skeletal muscle. These data suggest that these compounds have bypassed a defect in at least one of the signaling pathways leading to glucose transport. Furthermore, maximal transport rates induced by the simultaneous presence of insulin and phosphatase inhibitor in insulin-resistant muscle were equal to insulin-stimulated rates in lean control subjects. However, both vanadate alone and vanadate plus insulin stimulated 2 deoxyglucose transport significantly more in insulin-sensitive tissue than in insulin-resistant tissue. These results demonstrate that although vanadate is able to stimulate glucose transport in insulin-resistant muscle, it is not able to normalize transport to the same rate achieved in insulin-sensitive muscle. PMID- 7789632 TI - Effects of an acute increase in epinephrine and cortisol on carbohydrate metabolism during insulin deficiency. AB - This study was undertaken to investigate the effects of an acute increase in the plasma epinephrine level, with or without an accompanying increase in the plasma cortisol level, during selective insulin deficiency on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period, a 40-min basal period, and a 180-min experimental period. In all protocols, selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In EPI+SAL (n = 6), an additional infusion of epinephrine (0.04 micrograms.kg-1.min-1) was infused during the experimental period along with saline. In EPI+CORT (n = 6), hydrocortisone (3.0 microgram.kg-1.min-1) was infused in addition to epinephrine during the experimental period. In SAL+CORT (n = 5), hydrocortisone was infused during the experimental period. In SALINE (n = 5), neither epinephrine nor cortisol was infused. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production (rate of appearance [Ra]) and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in SALINE, the arterial plasma glucose level increased from 6.0 +/- 0.1 to 15.8 +/- 1.1 mmol/l; Ra increased from 14.7 +/- 0.7 to 24.9 +/- 1.7 mumol.kg-1.min-1. Gluconeogenic efficiency and the conversion of alanine and lactate to glucose increased to 300 +/- 55 and 355 +/- 67% of basal. In EPI+SAL and EPI+CORT, plasma glucose increased from 6.2 +/- 0.1 to 19.8 +/- 0.9 mmol/l and from 6.3 +/- 0.1 to 19.5 +/- 0.9 mmol/l. In EPI+SAL and EPI+CORT, Ra increased from 16.5 +/- 1.1 to 29.3 +/- 3.2 mumol.kg 1.min-1 and from 15.4 +/- 1.3 to 28.3 +/- 2.5 mumol.kg-1.min-1. The rise in gluconeogenic efficiency was similar to the rise that occurred in SALINE, but gluconeogenic conversion increased 17-fold in each of the two epinephrine groups. During the epinephrine infusion, gluconeogenesis accounted for a maximum of 55% of total glucose production as opposed to 31% during insulin deficiency alone. An increase in cortisol alone during insulin deficiency (SAL+CORT) had no effect on glucose level, glucose production, or gluconeogenesis. These results suggest that small increases in the plasma epinephrine level during insulin deficiency can significantly worsen the resulting hyperglycemia through stimulation of both glycogenolysis and gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789635 TI - Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle. AB - Insulin and muscle contraction stimulate glucose transport into muscle cells by separate signaling pathways, and hypoxia has been shown to operate via the contraction signaling pathway. To elucidate the mechanism of insulin resistance in human skeletal muscle, strips of rectus abdominis muscle from lean (body mass index [BMI] < 25), obese (BMI > 30), and obese non-insulin-dependent diabetes mellitus (NIDDM) (BMI > 30) patients were incubated under basal and insulin-, hypoxia-, and hypoxia + insulin-stimulated conditions. Insulin significantly stimulated 2-deoxyglucose transport approximately twofold in muscle from lean (P < 0.05) patients, but not in muscle from obese or obese NIDDM patients. Furthermore, maximally insulin-stimulated transport rates in muscle from obese and diabetic patients were significantly lower than rates in muscle from lean patients (P < 0.05). Hypoxia significantly stimulated glucose transport in muscle from lean and obese patients. There were no significant differences in hypoxia stimulated glucose transport rates among lean, obese, and obese NIDDM groups. Hypoxia + insulin significantly stimulated glucose transport in lean, obese, and diabetic muscle. The results of the present study suggest that the glucose transport effector system is intact in diabetic human muscle when stimulated by hypoxia. PMID- 7789634 TI - Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM. AB - Islet-1 (Isl-1) is a unique transcription factor that binds to the enhancer region of the insulin gene. To evaluate this gene in non-insulin-dependent diabetes mellitus (NIDDM), a full-length human Isl-1 cDNA was isolated and the genomic structure was characterized. The cDNA [2,395 bp plus additional poly(A) residues] contained an open reading frame from an initiator methionine at nucleotide 240 to an opal stop codon at nucleotide 1,286 (GenBank accession number UO7559), encoding a predicted protein of 349 amino acids (39 kDa). From their ends, 23 additional clones were sequenced, revealing 15 incomplete cDNAs and 8 intron-containing partially processed precursors. As determined by Northern blotting and reverse transcriptase-polymerase chain reaction analysis, Isl-1 was most abundantly expressed as a 2.4-kb mRNA in human islets, with a restricted pattern of expression in other adult human tissues. Analysis of genomic clones revealed that Isl-1 is encoded by six exons, varying in size from 168 bp (exon 5) to 1,230 bp (exon 6). Exons 2 and 3 each encode a LIM domain, while the homeodomain is completely contained within exon 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789636 TI - Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20. AB - This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. Ten marker-positive subjects and six matched nondiabetic marker-negative subjects from the RW family received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISR was derived by deconvolution of peripheral C peptide levels. Basal glucose and insulin levels were similar in marker-negative and marker-positive groups (5.3 +/- 0.2 vs. 5.0 +/- 0.2 mmol/l, P > 0.2, and 86.1 +/- 3.9 vs. 63.7 +/- 12.1 pmol/l, P > 0.1, respectively). However, the marker positive subjects had defective insulin secretory responses to an increase in plasma glucose concentrations. Thus, as the glucose concentration was raised above 7 mmol/l, the slope of the curve relating glucose and ISR was significantly blunted in the marker-positive subjects (13 +/- 4 vs. 68 +/- 8 pmol.min-1.mmol-1 x 1, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789637 TI - Lilly Lecture 1994. The beta-cell in diabetes: from molecular genetics to clinical research. AB - Pancreatic insulin secretion rates can be accurately derived by mathematical deconvolution of peripheral C-peptide concentrations either by using individual C peptide kinetic parameters obtained by analysis of the decay curve of biosynthetic human C-peptide or by using published group parameters with appropriate adjustments for age and degree of obesity. Since the cross-reactivity of proinsulin and related peptides is low (< 10%) in many C-peptide assays, this experimental approach avoids the spurious increase in insulin immunoreactivity resulting from cross-reactivity with proinsulin and related peptides in the insulin assay. Application of this technique has demonstrated that the phenotypic expression of beta-cell dysfunction differs in subjects with different genetic mechanisms of non-insulin-dependent diabetes mellitus (NIDDM). Subjects who have maturity-onset diabetes of the young (MODY) due to mutations in the glucokinase gene demonstrate different patterns of altered insulin secretion when compared with subjects who have mutations in the MODY1 gene on chromosome 20. Glucokinase mutations affect the ability of the beta-cell to detect and respond to small increases in glucose above the basal level. However, compensatory mechanisms operative in vivo, which include a priming effect of glucose on insulin secretion, limit the severity of the observed insulin secretory defect, resulting in a generally mild clinical course in these subjects. In contrast, mutations in the MODY1 gene are associated with an inability to increase insulin secretion as the plasma glucose concentration increases above 7-8 mmol/l and the normal priming effect of glucose on insulin secretion is lost. These characteristics of the dose-response relationships between glucose and insulin secretion result in a more severe degree of hyperglycemia than observed in subjects with glucokinase mutations, and these subjects more frequently need insulin treatment. These alterations are evident in prediabetic subjects with normal glucose levels who carry the MODY1 mutation, suggesting that defective beta-cell function is the primary pathogenetic defect in the diabetic syndrome in these subjects. Studies performed in the classic form of NIDDM demonstrate that subjects with mild glucose intolerance and normal fasting glucose concentrations and glycosylated hemoglobin levels consistently demonstrate defective beta-cell function. These results are consistent with studies in the Zucker diabetic fatty rat, an animal model of NIDDM in which prediabetic animals demonstrate extensive alterations in expression of multiple genes involved in the regulation of insulin secretion. It thus appears that abnormal beta-cell function is present at a relatively early stage in the evolution of NIDDM, even before the onset of overt hyperglycemia. PMID- 7789638 TI - Amelioration of high-fat feeding-induced insulin resistance in skeletal muscle with the antiglucocorticoid RU486. AB - Fat feeding produces whole-body insulin resistance and decreased glucose uptake in muscle tissue of rats. To examine the effect of glucocorticoid blockade on the insulin resistance caused by high-fat feeding, four groups of rats were fed diets high in starch (70% of calories) or fat (59% of calories) for 4 weeks with or without the antiglucocorticoid RU486 (69.8 mumol.kg-1.day-1) in the food. Whole body insulin action was assessed by the euglycemic clamp technique at an upper physiological insulin level with bolus 2-[3H]deoxyglucose to determine individual tissue insulin-stimulated glucose uptake. Whole-body glucose utilization (clamp glucose infusion rate [GIR]) was decreased by high-fat feeding (GIR 68.3 +/- 12.2 vs. 182.6 +/- 12.8 mumol.kg-1.min-1 for the starch-fed group; P < 0.001). Addition of RU486 to the diet significantly improved (GIR 133.9 +/- 12.8 mumol.kg 1.min-1; P < 0.01), but did not fully reverse, the insulin resistance caused by fat feeding. RU486 was without effect in the starch-fed rats. In skeletal muscles, RU486 ameliorated 62 and 68% of the insulin resistance produced by fat feeding in red quadriceps and extensor digitorum longus hindlimb muscles, respectively, but had no effect in heart or white adipose tissue. These results suggest that glucocorticoids play, in a tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by high-fat feeding. PMID- 7789639 TI - Microvascular function in human diabetes. A physiological perspective. AB - The late complications of diabetes represent in large part microvascular dysfunction. The development of techniques to measure microvascular function has resulted in a clearer picture of the stages of development of microangiopathy and the key pathophysiological processes involved. Considerable evidence supports the hemodynamic hypothesis of pathogenesis, which argues that early insulin-dependent diabetes is characterized by increased microvascular pressure and flow. Resultant injury to the microvascular endothelium causes adaptive microvascular sclerosis contributing to a loss of vasodilatory reserve and autoregulatory capacity with increasing disease duration. High susceptibility to microangiopathy appears to be characterized by both high capillary pressure and increased permeability, although the interrelationship between these variables needs to be better defined. In normotensive non-insulin-dependent diabetes subjects, a different pattern of microvascular functional abnormalities is apparent; it is hypothesized that these differences represent the impact of a prediabetic insulin-resistant phase on microvascular behavior and may in part explain the differential expression of vascular pathology in the two major types of diabetes. The physiological framework that has been defined reveals those pivotal processes upon which scientific attention should be centered and facilitates the generation of plausible molecular and cellular mechanisms that fit the physiological facts. PMID- 7789640 TI - An (A-C)n dinucleotide repeat polymorphic marker at the 5' end of the aldose reductase gene is associated with early-onset diabetic retinopathy in NIDDM patients. AB - To study the relationship between the aldose reductase gene and diabetic complications, an (A-C)n dinucleotide repeat sequence 2.1 kb upstream of the transcription start site of this gene was identified and studied. There are seven alleles at this locus with a polymorphism information content of 0.73 and a heterozygosity of 0.77 among the Chinese population in Hong Kong. One of the alleles (Z-2) was found to be associated with early onset of retinopathy in patients with non-insulin-dependent diabetes (P = 0.007), suggesting that aldose reductase or a gene in the close vicinity may be involved in the pathogenesis of this diabetic complication. PMID- 7789641 TI - Unchanged incidence of diabetic nephropathy in IDDM patients. AB - Recently, a dramatic decline in the cumulative incidence of diabetic nephropathy (< 10% after 25 years of diabetes) has been reported in insulin-dependent diabetes mellitus (IDDM) patients diagnosed before the age of 15 years between 1961 and 1980. In a clinic-based study, we assessed recent trends in the incidence of diabetic nephropathy. All 356 patients in whom IDDM was diagnosed before the age of 41 years between 1965 and 1979, identified in 1984, were followed until 1991 or until death. All patients were Caucasians and resided in Copenhagen. The cumulative incidences (life-table method) of diabetic nephropathy (urinary albumin excretion > or = 300 mg/24 h in two out of three consecutive samples) after 15 years of diabetes and in 1991 were 18 +/- 4 and 35 +/- 5% (cumulative incidence +/- SE; onset of diabetes 1965-1969, n = 113), 20 +/- 4 and 35 +/- 5% (onset of diabetes 1970-1974, n = 130), and 16 +/- 5% (onset of diabetes 1975-1979, n = 113), respectively (NS at 15 years). The prevalence of persistent microalbuminuria (31-299 mg/24 h) at time of follow-up was 24% (95% confidence interval: 16-33) in the group with onset of diabetes in 1965-1969, 28% (20-36) with onset of diabetes in 1970-1974, and 19% (13-28) with onset of diabetes in 1975-1979 (NS). The mean +/- SE HbA1c measured yearly beginning in 1984 was higher in patients with nephropathy (9.4 +/- 0.1%) and persistent microalbuminuria (8.9 +/- 0.1%) than in patients with normoalbuminuria (8.5 +/- 0.1%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789642 TI - Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes. AB - Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by being involved in the extravasation of lymphocytes from the circulation into the inflamed pancreas. However, the mechanism of beta-cell destruction by which expression of ICAM-1 on beta-cells may facilitate adhesion of effector cells still remains to be elucidated. Several lines of evidence suggest that this adhesion molecule is involved in the destruction of pancreatic beta-cells by killer lymphocytes in the NOD mouse, which shows an autoimmune diabetic syndrome similar to that of human IDDM. Immunohistochemical study under light microscopy demonstrated that all of the mononuclear cells infiltrating the islets strongly expressed ICAM-1 and leukocyte function-associated antigen 1 (LFA-1), a counterreceptor of ICAM-1, whereas ICAM-1 expression on islet cells was not apparent. However, immunohistochemical staining under electron microscopy revealed that islet beta cells adjacent to infiltrating lymphocytes were clearly stained by an anti-ICAM-1 monoclonal antibody (mAb). Flow cytometric analysis showed that the ICAM-1 expression on NOD islet cells and NOD-derived insulinoma cells (MIN6N8a) was inducible by interferon (IFN)-gamma or tumor necrosis factor-alpha. These cytokines had an additive effect on the ICAM-1 induction. Susceptibility of MIN6N8a cells to lysis by a NOD islet-derived CD8+ cytotoxic T-cell clone was greatly enhanced by IFN-gamma pretreatment, and this enhancement was abolished by anti-ICAM-1 and anti-LFA-1 mAbs. When both mAbs were administered into NOD mice with spontaneous or adoptively transferred diabetes, the development of diabetes was significantly prevented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789643 TI - Glomerular mesangial cell altered contractility in high glucose is Ca2+ independent. AB - In diabetes, loss of renal arteriolar smooth-muscle cell contractility leads to intraglomerular hypertension. In glomeruli isolated from streptozotocin (STZ) induced diabetic rats, the mesangial cells (smooth muscle-like) display loss of contractile responsiveness to angiotensin II. This study examines the mechanistic relationship between altered mesangial cell contractility and vasopressor hormone stimulated Ca2+ signaling in high glucose. Glomeruli were isolated from normal or STZ-induced diabetic rats to observe ex vivo mesangial cell contractile function. Also, rat mesangial cells were cultured (10-20 passages) in normal (5.6 mmol/l) or high (10-25.6 mmol/l) glucose for 1-5 days. Reduction of glomerular volume and decreased planar surface area of cultured mesangial cells in response to vasoconstrictor stimulation over 60 min were measured by videomicroscopy and personal computer-based morphometry. Contraction of glomeruli isolated from STZ administered rat in response to endothelin (ET)-1 (0.1 mumol/l) or the Ca2+ ionophore A23187 (5 mumol/l) was impaired significantly compared with that in normal glucose. In the presence of arginine vasopressin (AVP) (1.0 mumol/l) or ET 1 (0.1 mumol/l), mesangial cells demonstrated a dose-dependent loss of contractile response to increasing glucose concentrations (5.6-25.6 mmol/l) within 24 h of high-glucose exposure, which was sustained for 5 days. Mesangial cells in high glucose were consistently smaller in size compared with those in normal glucose. Mesangial cells were preloaded with myo-[2-3H]inositol and intracellular [3H] inositol phosphate release in response to AVP (1.0 mumol/l) was analyzed by Dowex chromatography. Comparing cells in normal (5.6 mmol/l) verus high (25.6 mmol/l) glucose, we observed no significant difference in stimulated inositol phosphate levels from 10 to 60 s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789644 TI - Glucagon-like peptide I increases cytoplasmic calcium in insulin-secreting beta TC3-cells by enhancement of intracellular calcium mobilization. AB - In the insulin-secreting beta-cell line beta TC3, stimulation with 11.2 mmol/l glucose caused a rise in the intracellular free Ca2+ concentration ([Ca2+]i) in only 18% of the tested cells. The number of glucose-responsive cells increased after pretreatment of the cells with glucagon-like peptide I (GLP-I)(7-36)amide and at 10(-11) mol/l; 84% of the cells responded to glucose with a rise in [Ca2+]i. GLP-I(7-36)amide induces a rapid increase in [Ca2+]i only in cells exposed to elevated glucose concentrations (> or = 5.6 mmol/l). The action of GLP I(7-36)amide and forskolin involved a 10-fold increase in cytoplasmic cAMP concentration and was mediated by activation of protein kinase A. It was not associated with an effect on the membrane potential but required some (small) initial entry of Ca2+ through voltage-dependent L-type Ca2+ channels, which then produced a further increase in [Ca2+]i by mobilization from intracellular stores. The latter effect reflected Ca(2+)-induced Ca2+ release and was blocked by ryanodine. Similar increases in [Ca2+]i were also observed in voltage-clamped cells, although there was neither activation of a background (Ca(2+)-permeable) inward current nor enhancement of the voltage-dependent L-type Ca2+ current. These observations are consistent with GLP-I(7-36) amide inducing glucose sensitivity by promoting mobilization of Ca2+ from intracellular stores. We propose that this novel action of GLP-I(7-36)amide represents an important factor contributing to its insulinotropic action. PMID- 7789645 TI - Bone loss and bone turnover in diabetes. AB - There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; approximately 12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured approximately 2.5 years (41 patients) and approximately 12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck approximately 12 years later was > 0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards age-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789646 TI - On the mechanisms of blunted nocturnal decline in arterial blood pressure in NIDDM patients with diabetic nephropathy. AB - Nondiabetic hypertensive patients lacking the normal nocturnal decline in arterial blood pressure have enhanced cardiovascular complications. Since cardiovascular morbidity and mortality are increased in non-insulin-dependent diabetes mellitus (NIDDM), we performed a prospective cross-sectional case controlled study comparing the diurnal variation in arterial blood pressure, prevalence of dippers, cardiac autonomic nervous function (beat-to-beat variation during deep breathing), and extracellular fluid volume (51Cr-labeled EDTA) in 55 NIDDM patients with diabetic nephropathy (group 1), 55 NIDDM patients with normoalbuminuria (group 2), and 22 nondiabetic control subjects (group 3). All antihypertensive treatments were withdrawn at least 2 weeks before the study. The nocturnal blood pressure reduction (daytime-to-nighttime)/daytime (mean +/- SE) was impaired in group 1 (6.6 +/- 1.5%) and group 2 (11.1 +/- 1.4%) as compared with group 3 (17.6 +/- 1.7%), and it was impaired in group 1 as compared with group 2 (P < 0.05 for each comparison). The prevalence of dippers (95% confidence interval) was lower in group 1 (42% [29-56]) as compared with group 2 (58% [44 71]; P = 0.08) and group 3 (86% [65-97]; P < 0.001) and in group 2 as compared with group 3 (P < 0.01). Abolished beat-to-beat variation was more prevalent in group 1 (63% [50-76]) as compared with group 2 (15% [7-27]) and with group 3 (5% [0-23]) (P < 0.001). Nocturnal blood pressure reduction was associated with beat to-beat variation during deep breathing (r = 0.22, P < 0.01). Extracellular fluid volume (mean +/- SE) was higher in group 1 (15.9 +/- 0.5 l/m2) as compared with group 3 (14.1 +/- 0.8 l/m2) (P < 0.05) with group 2 between the two (15.1 +/- 0.4 l/m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789647 TI - Diabetic ketoacidosis in obese African-Americans. AB - Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789648 TI - The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVI. The relationship of C-peptide to the incidence and progression of diabetic retinopathy. AB - The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy. PMID- 7789649 TI - 31P-nuclear magnetic resonance evidence of an activated hexose-monophosphate shunt in hyperglycemic rat lenses in vivo. AB - Using 31P-nuclear magnetic resonance spectroscopy, we have identified elevated concentrations of sedoheptulose-7-phosphate (S-7-P) in lenses from three animal models of hyperglycemia: streptozotocin-induced diabetic rats, galactose-fed rats, and xylose-fed rats. This observation provides a unique and independent confirmation of the activation of the hexose monophosphate shunt (HMPS) pathway in the hyperglycemic lens in vivo. While the elevation in concentration of S-7-P was very dramatic, the other HMPS metabolites in these tissues were below the threshold of detection, as expected for the HMPS pathway near equilibrium. In terms of nonenzymatic glycation, these results suggest that the only HMPS metabolite of importance in the hyperglycemic rat lens is S-7-P. Although in the diabetic lens its role appears to be relatively minor, in the galactosemic lens this compound may be an important contributor to the increased production of advanced glycosylation end products. PMID- 7789650 TI - Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes. AB - Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23], microalbuminuria [12], or macroalbuminuria [12]) and retinopathy (none [13], background [20], or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (< or = 28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P < 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789651 TI - The pseudotetrasaccharide acarbose inhibits pancreatic islet glucan-1,4-alpha glucosidase activity in parallel with a suppressive action on glucose-induced insulin release. AB - The pseudotetrasaccharide acarbose, previously known as a potent inhibitor of intestinal alpha-glucoside hydrolases, was investigated with regard to its influence on islet lysosomal enzyme activities and the insulin secretory processes. We observed that acarbose was a potent inhibitor of mouse islet lysosomal acid glucan-1,4-alpha-glucosidase activity, EC50 approximately 5 mumol/l, as well as of acid alpha-glucosidase activity. In contrast, acarbose did not influence other lysosomal enzyme activities such as acid phosphatase and N acetyl-beta-D-glucosaminidase. Neutral alpha-glucosidase (endoplasmic reticulum) was only moderately inhibited in homogenate and was unaffected in intact islets. Incubation of isolated mouse islets with acarbose revealed that the pseudotetrasaccharide was a strong inhibitor of glucose-induced insulin secretion, EC50 approximately 500 nmol/l, and a significant inhibition was already observed at a concentration of acarbose as low as 100 nmol/l. The acarbose analogue maltotetrose did not influence either glucose-induced insulin release or islet lysosomal enzyme activities. Further, acarbose as well as two other alpha-glucoside hydrolase inhibitors, the deoxynojirimycin derivatives miglitol and emiglitate, did not affect islet glucose oxidation at low or high glucose levels. Acarbose also inhibited insulin release induced by the sulfonylurea glibenclamide, whereas insulin secretion stimulated by the cholinergic muscarinic agonist carbachol or the phosphodiesterase inhibitor isobutylmethylxanthine was unaffected by the drug. Moreover, complementary in vivo experiments showed that pretreatment of mice with acarbose to allow for endocytosis of the compound markedly suppressed the insulin secretory response to an intravenous glucose load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789652 TI - Defective insulin action on protein and glucose metabolism during chronic hyperinsulinemia in subjects with benign insulinoma. AB - The ability of chronic endogenous hyperinsulinemia to induce a resistance to insulin action on protein and glucose metabolism was studied in 10 subjects affected by a benign (functioning) insulinoma and 18 healthy subjects by means of infusions of [1-(14)C]leucine and [3-(3)H] glucose. The insulinoma subjects were divided into two groups with moderate (139 +/- 12 pmol/l) (n = 5) and marked (438 +/- 42 pmol/l) (n = 5) hyperinsulinemia and were studied during a euglycemic dextrose infusion. Control subjects were studied postabsorptively and during a low-dose (0.3 mU.kg-1.min-1) (n = 3) and a high-dose (1 mU.kg-1.min-1) (n = 15) euglycemic insulin clamp to match peripheral insulin concentrations with those of insulinoma subjects. In insulinoma subjects there was no correlation among plasma insulin concentration and leucine concentration (r = 0.05), endogenous leucine flux (r = 0.44), hepatic glucose production (r = 0.47), and glucose uptake (r = 0.05). Insulinoma subjects with marked hyperinsulinemia demonstrated a defective suppression of leucine concentrations (100 +/- 11 vs. 65 +/- 5 mumol/l, P < 0.01), endogenous leucine flux (50.1 +/- 6.3 vs. 27.1 +/- 0.9 mumol.m-2.min-1, P < 0.01), and hepatic glucose production (5.4 +/- 2.0 vs. 0.6 +/- 0.6 mumol.kg 1.min-1, P < 0.05), and a defective stimulation of glucose uptake (13.5 +/- 1.6 vs. 41.1 +/- 2.8 mumol.kg-1.min-1, P < 0.001) with respect to normal subjects at a comparable degree of hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789653 TI - Estimation of beta-cell sensitivity from intravenous glucose tolerance test C peptide data. Knowledge of the kinetics avoids errors in modeling the secretion. AB - Parametric models of insulin secretion are used to measure indexes of beta-cell function from plasma C-peptide concentration during an intravenous glucose tolerance test (IVGTT). Since the models have been usually assessed against plasma C-peptide data, both secretory and kinetic parameters need to be simultaneously estimated. However, undesired compensations between the two sets of parameters may arise. In this study, in order to evaluate IVGTT insulin secretion models, we have analyzed IVGTT data from seven normal subjects for whom individual C-peptide kinetics were known from a separate experiment. Three different beta-cell models have been examined: the minimal model M1 (Diabetes 37:223-231, 1988); a variation of a published model, M2 (Math Biosci 27:319-332, 1975); and a new one, M3. A two-compartment model was used to describe C-peptide kinetics. The results suggest the inadequacy of M1 since kinetic parameter estimates were consistently biased versus the known individual values, and systematic errors were present in the prediction of C-peptide data when kinetic parameters were fixed to the known individual values. M2 performs better than M1 since it reproduces C-peptide data satisfactorily when the individually known description of the kinetics is adopted. M3 retains the second-phase description of M2 but improves the description of first-phase release. M3 is thus proposed to reconstruct the insulin secretion time course and to estimate parameters of first and second-phase sensitivity to glucose. We also show the robustness of M3, i.e., standard values of C-peptide kinetic parameters can be used when individual values are not available without a loss of accuracy in the estimated secretion parameters. Finally, the shortcomings of using a simplified single-compartment description of C-peptide kinetics are discussed. PMID- 7789654 TI - Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. AB - The obese (ob) gene, the mutation of which results in severe hereditary obesity and diabetes in mice, has recently been isolated through positional cloning. In this study, we isolated a full-length human ob complementary DNA (cDNA) clone and examined the tissue distribution of ob gene expression in humans. The nucleotide sequences of the human ob cDNA coding region were 83% identical to those of the mouse and rat ob cDNA coding regions. Analysis of the deduced amino acid sequences revealed that the human ob protein is a 166-amino acid polypeptide with a putative signal sequence and is 84 and 83% homologous to the mouse and rat ob proteins, respectively. Northern blot analysis using the cloned human ob cDNA fragment as a probe identified a single messenger RNA (mRNA) species 4.5 kb in size found abundantly in the adipose tissues obtained from the subcutaneous, omental, retroperitoneal, perilymphatic, and mesenteric fat pads. However, no significant amount of ob mRNA was present in the brain, heart, lung, liver, stomach, pancreas, spleen, small intestine, kidney, prostate, testis, colon, or skeletal muscle. The ob mRNA level in the adipose tissue varied from region to region even in the same individual. Furthermore, in the human adipose tissue, ob gene expression occurred in mature adipocytes rather than in stromal-vascular cells. This study is the first report of the elucidation of ob gene expression in human tissues, thereby leading to better understanding of the physiological and clinical implications of the ob gene. PMID- 7789656 TI - Disclosure. PMID- 7789655 TI - The prevention of IDDM. Injecting insulin into the cytokine network. PMID- 7789658 TI - Nature of the brain lesion in fetal allo-immune thrombocytopenia. AB - Study of three fetuses with allo-immune thrombocytopenia, one with autopsy findings, and comparison with existing data have permitted speculation on the nature of the initial lesion within the brain. The commonest first bleeding site is probably underneath the molecular layer of the cerebral cortex, often within the temporal lobe. Small haemorrhages may appear to be (sub)pial, but expansion will lead to so-called subarachnoid haematoma. Communication with the adjacent lateral ventricle will contribute to post-haemorrhagic hydrocephalus. Occasionally, the initial haemorrhage is within the ventricle; such a pattern may lead to post-haemorrhagic hydrocephalus, often with a porencephalic component. In utero follow-up of fetuses at risk for allo-immune thrombocytopenia will have to focus on superficial cerebral haemorrhage for early detection of brain involvement. PMID- 7789659 TI - Visual function in Rett syndrome. AB - The authors examined refractive error, pattern onset visual evoked potentials, ocular posture and they performed internal and external eye examinations in 11 subjects with Rett syndrome (aged between four and 24 years) and 18 normal controls (aged between six and 20 years). Substantial refractive errors were common in the Rett syndrome group. Spectacle correction had never previously been worn and glasses were provided where appropriate. No subjects had nystagmus or optic nerve pallor and only one was strabismic. All subjects had recognisable and reproducible pattern-onset VEPs and latencies and amplitudes did not differ significantly from those of the controls. All demonstrated VEP thresholds of at least 24'. In contrast to other populations with profound disabilities, people with Rett syndrome have good function of the afferent visual pathways and, in view of their substantial refractive errors, are likely to benefit from spectacle correction. PMID- 7789657 TI - Prevention by magnesium of excitotoxic neuronal death in the developing brain: an animal model for clinical intervention studies. AB - Excitotoxic disturbances during brain development were studied in the mouse using intracerebral injections of ibotenate, a glutamatergic agonist of the N-methyl-D aspartate (NMDA) complex receptor, to analyse the protective effect of a systemic bolus of MgSO4, a non-competitive antagonist of the NMDA ionophore-complex receptor. MgSO4 did not prevent microgyia, induced by ibotenate when injected at P0 immediately after the post-migratory settlement of layer V, but did prevent ulegyrias, porencephalic cysts, and other cortical and cortical-subcortical hypoxic-like lesions arising after completion of the neocortical cyto architectonic development at P5. Protection was optimal in 80 per cent of mice at 600mg/kg, with no mortality due to MgSO4; thereafter mortality increased with dosage. The protective effect appears after the developmental acquisition of two properties of the excitotoxic cascade, namely the coupling of the massive calcium influx with NMDA-receptor overstimulation and the predominance of magnesium obliterable calcium channels. This animal model supports the clinical intervention studies with magnesium in hypoxias/perfusion failures and has implications for their design. If maturation of the excitotoxic cascade follows the same sequence in humans, protection is probably low before 26 weeks of gestational age. PMID- 7789660 TI - The maturation of linear acuity and compliance with the Sonksen-Silver Acuity System in young children. AB - The compliance and maturation of visual acuity of 1245 2 1/2- to nine-year-olds was investigated. Testing was undertaken as part of routine surveillance. Ability to letter match, to achieve a binocular measure and to achieve monocular measures for children under three years was 89, 78 and 37 per cent, for children aged three to four years 97, 91 and 66 per cent, and for children over four years 99.9, 99.9 and 99, respectively. A statistical model was developed to give acuity norms by age for use by surveillance and diagnostic teams. PMID- 7789661 TI - Measures of acuity in primary-school children and their ability to detect minor errors of vision. AB - 492 five to nine year old children participated in a study of the ability of three tests of linear acuity --the Sonksen-Silver Acuity System (SSAS), the Sheridan Gardiner 7-letter chart and the Keelers MK2 chart to identify children requiring specialist visual examination. The ability of the three tests to detect children with visual defects at 6m and of the SSAS in several test test conditions (3m and 6m, monocular and binocular) was investigated at two acuity levels for referral (3/4.5 or 6/9 and 3/6 or 6/12). Although specificity was very high for all tests and test conditions using a 3/6 or 6/12 cut-off for referral, the sensitivity and yield were disappointingly low; higher levels of the latter were achieved at the expense of a degree of specificity using a 3/4.5 or 6/9 cut off. Similarly, sensitivity and yield were greater for the monocular than binocular condition and for the 6m than 3m condition. A test of near vision (SSAS) did not detect any children not already identified by a distance measure. The optometric and developmental rationale behind the differences is discussed. PMID- 7789663 TI - A study of a dynamic proximal stability splint in the management of children with cerebral palsy. AB - This paper describes a study of the UPsuit, a proximal stability splint fabricated from Lycra, in the management of children with cerebral palsy. The splint improved posture and reduced involuntary movement immediately. The amount of functional improvement depended on the type and severity of impairments, the subject's attitude, their capacity for purposeful intent and compliance. Compromised lung function and pre-existing hypoactivity were medical contra indications to UPsuit wear whilst a limited capacity for purposeful intent or a negative attitude restricted benefits. The Upsuit was of great value to one quarter of subjects, but Lycra splinting may benefit a wider spectrum of persons with cerebral palsy in the form of less intrusive splints applied to the limbs. PMID- 7789662 TI - Effect of oral sensorimotor treatment on measures of growth, eating efficiency and aspiration in the dysphagic child with cerebral palsy. AB - Twenty-seven children (mean age 5.1 years) with cerebral palsy and moderate eating impairment were studied to determine frequency of aspiration and the effect of 10 and 20 weeks of oral sensorimotor therapy on eating efficiency and measures of growth (weight, skinfold thickness). The eating efficiency of the children did not change markedly in response to oral sensorimotor therapy. Children maintained their centile rank in weight-for-age and skinfold-for-age measurements. However, there was no catch-up growth. The findings suggest that eating efficiency is not a good estimator of treatment outcome, but rather a diagnostic indicator of the severity of eating impairment. Monitoring of these children's growth is essential in order to provide nutritional rehabilitation as soon as their eating skills can no longer keep up with growth demands. PMID- 7789664 TI - Prenatal brain damage and placental infarction--an autopsy study. AB - The histopathological abnormalities seen at autopsy in the brains and corresponding placentas of a consecutive four-year series of stillborn infants are presented. After excluding stillbirths with major cerebral malformations, the brains of 175 cases and the corresponding placentas in 165 cases were available for assessment. 70 of the 175 brains (40 per cent) showed microscopic evidence of ischaemic cerebral injury, using a combination of haematoxylin-eosin and glial fibrillary acid protein stains. In 62 of these 70 brains, the periventricular white matter was the main site of damage. 46 (28 per cent) of the corresponding 165 placentas showed macroscopic and microscopic evidence of infarction, 39 of which were associated with ischaemic cerebral lesions. It was concluded that placental infarcts are commonly associated with prenatal cerebral ischaemic lesions. PMID- 7789665 TI - Relation between Asperger syndrome and prosopagnosia. PMID- 7789666 TI - Cross-talk in otoacoustic emission probes. AB - OBJECTIVE: Several commercial otoacoustic emission probes (Virtual 330, Etymotic Research ER-10 and ER-10B, and Otodynamics ILO88 and ILO92) were tested for internal coupling (cross-talk) between the sound source and probe microphone. DESIGN: The response of the probe under test was measured, in a cavity that simulates the human ear canal, first in its normal configuration and then with either the sound source tube or the microphone inlet blocked with modelling clay. Cross-talk was indicated if the pressure failed to drop substantially in the "blocked" condition. RESULTS: Cross-talk in the Virtual 330 and Etymotic ER-10B was found to be severe enough to compromise the accuracy of "in the ear" acoustic calibrations. In both cases the cause was the radiation of sound through the walls of the flexible silicone tubing used to conduct the stimuli through the body of the probe. Substituting harder-walled sound source tubing reduced cross talk to levels acceptable for routine application. The probes used in the otodynamics ILO88 and ILO92 systems and the original Etymotic ER-10 probes all have acceptably low cross-talk as supplied from the manufacturers. CONCLUSIONS: For the two probes where excessive cross-talk was found, most of the cross-talk was acoustic and/or mechanical, rather than electromagnetic. Artifacts due to cross-talk have undoubtedly contaminated data collected with these units. Manufacturers of emission probes are urged to adopt a standard for specifying cross-talk levels and include this specification in product literature. PMID- 7789667 TI - Growth of the 2f1-f2 distortion product otoacoustic emission for low-level stimuli in human neonates. AB - Distortion product otoacoustic emissions (DPOAEs) for low stimulus levels (< 60 dB SPL) have been reported in adult humans under ideal conditions. In neonates, DPOAEs have been reported only for high-level stimuli. The purpose of this paper was to determine characteristics of the 2f1-f2 DPOAE for low-level stimuli in neonates and to assess the feasibility of obtaining such measures in a noisy environment. Subjects were 19 premature neonates presumed to have normal hearing based on systematic pneumatic otoscopy measures and evoked auditory brainstem responses. For stimuli centered at 2000 and 6000 Hz and presented over a range of 30 to 75 dB SPL, DPOAEs were measured employing linear time averaging for up to 128 time frames at each level. In quiescent subjects, the level of the noise floor was as low as that reported in cooperative adults under ideal conditions (approximately -30 dB SPL), and the functions were identical. That is, valid measures were obtained for very low stimulus levels (30 dB SPL), the rate of growth approached 1 dB/dB, and identical nonmonotonicities (saturation, plateaus, and notches) were observed as those reported for adults. When the noise floor was elevated due to subject activity, no valid data could be obtained for low-level stimuli even though the DPOAEs were at expected levels for high-level stimuli. These results have important implications for the use of such measures in this population because the DPOAEs associated with the metabolically active nonlinear cochlear processes at low stimulus levels may be contaminated with DPOAEs associated with other processes at high stimulus levels. PMID- 7789668 TI - Quantifying improvement with amplification. AB - We employed a nonparametric measure, the randomization test, to evaluate, statistically, a variety of speech understanding measures used to quantify the efficacy of different intervention strategies in five clinical patients. The flexibility of the approach was demonstrated by comparing monaural with binaural amplification, a conventional aid with an assistive listening device, and a cochlear implant alone versus a cochlear implant supplemented by visual cues. The randomization test allows statistical analysis of differences in performance at the level of the individual subject. This approach may be useful in addressing accountability when recommending a specific intervention strategy for a particular hearing-impaired individual. PMID- 7789669 TI - The abbreviated profile of hearing aid benefit. AB - OBJECTIVE: To develop and evaluate a shortened version of the Profile of Hearing Aid Benefit, to be called the Abbreviated Profile of Hearing Aid Benefit, or APHAB. DESIGN: The Profile of Hearing Aid Benefit (PHAB) is a 66-item self assessment, disability-based inventory that can be used to document the outcome of a hearing aid fitting, to compare several fittings, or to evaluate the same fitting over time. Data from 128 completed PHABs were used to select items for the Abbreviated PHAB. All subjects were elderly hearing-impaired who wore conventional analog hearing aids. Statistics of score distributions and psychometric properties of each of the APHAB subscales were determined. Data from 27 similar subjects were used to examine the test-retest properties of the instrument. Finally, equal-percentile profiles were generated for unaided, aided and benefit scores obtained from successful wearers of linear hearing aids. RESULTS: The APHAB uses a subset of 24 of the 66 items from the PHAB, scored in four 6-item subscales. Three of the subscales, Ease of Communication, Reverberation, and Background Noise address speech understanding in various everyday environments. The fourth subscale, Aversiveness of Sounds, quantifies negative reactions to environmental sounds. The APHAB typically requires 10 minutes or less to complete, and it produces scores for unaided and aided performance as well as hearing aid benefit. Test-retest correlation coefficients were found to be moderate to high and similar to those reported in the literature for other scales of similar content and length. Critical differences for each subscale taken individually were judged to be fairly large, however, smaller differences between two tests from the same individual can be significant if the three speech communication subscales are considered jointly. CONCLUSIONS: The APHAB is a potentially valuable clinical instrument. It can be useful for quantifying the disability associated with a hearing loss and the reduction of disability that is achieved with a hearing aid. PMID- 7789670 TI - Use of test-retest measures to evaluate performance stability in adults with cochlear implants. AB - OBJECTIVE: This study was designed to evaluate performance stability with test retest measures of electrical thresholds, electrical maximum acceptable loudness levels, sound-field thresholds, and audition-only speech tests. The hypothesis was that the standard error of measurement differs from one individual to another for each test, and therefore test-retest measures need to be obtained from each subject. DESIGN: Test-retest data were obtained in three sets. For the first two sets, data were obtained over 4 successive weeks to determine day-to-day variability. The third set was obtained on 2 successive days, 2 to 10 months later at each subject's annual evaluation. The seven subjects were recipients of the Nucleus cochlear implant and used the Mini Speech Processor at least one year. They were selected because they were available for research testing. RESULTS: The ranges of electrical thresholds and maximum acceptable loudness levels obtained from each subject during the first two sets were substantially larger on some electrodes than on others. Between set 1 and set 2 for each subject, there were significant differences between thresholds and between maximum acceptable loudness levels on some electrodes. For thresholds as well as maximum acceptable loudness levels, the standard error of measurement across the three sets and 10 electrodes differed among subjects. The group standard error of measurement for sound-field thresholds was small (2 dB). The group standard error of measurement for the NU-6 word test scored according to phonemes (2.75%) was less than half that for the vowel (6.06%) and consonant (5.67%) tests. The standard error of measurement for each speech test differed among subjects. CONCLUSIONS: The standard error of measurement for thresholds as well as maximum acceptable loudness levels varies among electrodes in the same subject and among subjects across electrodes. The standard error of measurement also varies among speech tests for the group as well as among subjects for each speech test. There is little variation in test-retest measures of sound-field thresholds among subjects. These results suggest the clinical importance of obtaining test-retest measures for evaluating the stability of electrical thresholds, electrical maximum acceptable loudness levels, and speech tests. PMID- 7789671 TI - Comparison of two multichannel tactile devices as supplements to speechreading in a postlingually deafened adult. AB - OBJECTIVE: The purpose of this study was to conduct a single-subject comparison of the effectiveness of two multichannel vibrotactile devices that encode different classes of speech information. One device, the Portapitch, is designed to convey fundamental frequency (F0) and its variation over time. The other, the TACTAID 7, is designed to convey the first two formant frequencies (F1 and F2) and their variation over time. DESIGN: The subject, a postlingually deafened adult, underwent an intensive 17-wk training and testing protocol with the Portapitch and then completed a similar 17-wk protocol with the TACTAID 7. Performance measures were obtained on phonetic-contrast perception by speechreading alone, tactile device alone, and speechreading plus tactile device, and on open-set word and sentence recognition by speechreading alone and speechreading plus tactile device. RESULTS: On phonetic-contrast testing, the subject demonstrated some ability to perceive voicing, stress, and intonation contrasts using the Portapitch, but gave little evidence of phonetic-contrast perception with the TACTAID 7. On open-set word recognition testing, no significant improvements were seen with either device. On open-set sentence recognition testing, the subject showed a significant 9 percentage point enhancement effect using the Portapitch; the mean 5 percentage point enhancement effect provided by the TACTAID 7 was not statistically significant. CONCLUSIONS: A small advantage was seen in favor of the tactile display of F0 relative to the tactile display of formant frequency information on both phonetic-contrast testing and open-set sentence recognition. The difference, however, was of questionable significance and could have been confounded with an order effect. Nevertheless, the subject's preference was for the tactile formant frequency display. PMID- 7789672 TI - Articulation accuracy of children using an electrotactile speech processor. AB - OBJECTIVE: Use of wearable tactile speech perception devices is suggested to help overcome the difficulties in speech production resulting from severe and profound hearing impairment in children. This suggestion is based on the assumption that subjects can use tactile input in isolation, or in combination with information from residual aided hearing, to monitor and modify their speech. The present study evaluated the benefits to articulation provided through use of a multichannel electrotactile device ("Tickle Talker"). DESIGN: Six profoundly hearing-impaired children were videotaped speaking with the Tickle Talker on and with the Tickle Talker off during conversations with their audiologist. Five of the subjects also wore their binaural hearing aids during all recorded conversations. The number of vowels, consonants, and overall phonemes correctly articulated by each child in the two conditions were compared. RESULTS: One subject improved articulation of initial consonants and initial phonemes; one subject improved articulation of total vowels, total consonants, initial consonants, total phonemes, and initial phonemes; and a third subject improved articulation of total vowels and medial phonemes. CONCLUSIONS: Use of on-line tactile feedback from the Tickle Talker may benefit the articulation accuracy of some children, and the device may therefore be suitable to use with children who have not responded to more traditional speech training techniques. PMID- 7789673 TI - A test of virtual auditory localization. AB - OBJECTIVE: The purpose of this study was to evaluate a test of virtual auditory localization including assessment of its ease of administration and its sensitivity to differences in binaural performance in children and adults. This test eliminates many potential problems inherent in any free-field localization test such as calibration problems, problems replicating source and listener locations, and issues associated with head movements. DESIGN: Binaural performance was measured using the virtual localization test and a simple binaural detection task, the masking-level difference (MLD), for three groups of subjects: adults, children with a negative history of otitis media, and children with a positive history of otitis media. There were five subjects in each group. The adults were all student volunteers; the children were recruited first and subsequently placed into groups based on their medical histories obtained from their physicians and parental reports. RESULTS: Results indicate that this test of virtual auditory localization is useful for measuring binaural performance in children and adults and is sensitive to differences in binaural processing. Performance of the adults and children with a negative history of otitis media was comparable on both of the binaural tests, and on the binaural detection task, was similar to that reported in the literature for normal-hearing listeners; but the children with a positive history of otitis media performed more poorly on both tests. CONCLUSIONS: The results of this study indicate that the virtual localization test described here is easy to administer to children and adults. The signal processing techniques used in this virtual auditory localization test lend themselves to straightforward comparisons across different laboratories and clinics and make this test a potentially useful clinical tool. The development of such a clinical test is currently under study. PMID- 7789674 TI - Central auditory processing in Alzheimer's disease. AB - OBJECTIVE: This investigation was designed to determine whether people in the early to middle phases of Alzheimer's disease (AD) show impaired central auditory processing as compared with nondemented elderly. DESIGN: A peripheral and central auditory test battery was administered to 10 subjects diagnosed with mild-to moderate AD based on a neuropsychological test battery and radiographic techniques, and a control group of 10 subjects with no evidence of dementia, matched for age, gender, and average degree of hearing loss. Immittance audiometry, pure-tone and speech audiometry, and otoacoustic emissions were recorded in all subjects. Central auditory assessment included the synthetic sentence identification with ipsilateral competing message, dichotic digits, dichotic sentence identification, pitch patterns, and duration patterns. RESULTS: Peripheral auditory status was statistically similar between subject groups. Neither average high frequency hearing sensitivity nor mean speech recognition ability was significantly different. However, a significant difference was noted between groups for average low frequency hearing sensitivity in the left ear (p < 0.05). Subjects with AD showed slightly poorer low frequency thresholds versus matched controls. Based on analysis of performance on each measure of the central auditory test battery, the AD group scored significantly lower than the matched control group on four of the five measures utilized. Differences for right versus left ear performance were found among AD subjects. CONCLUSIONS: Overall patterns in findings cannot be easily explained as artifacts of cognitive decline. Results support screening for central auditory dysfunction in the AD population, since impaired processing could influence psychiatric assessment of cognitive deficit as well as audiologic management of peripheral hearing loss in this population. PMID- 7789675 TI - Prospective randomized comparison of polyvinyl bougies and through-the-scope balloons for dilation of peptic strictures of the esophagus. AB - We prospectively compared the efficacy of polyvinyl bougies (Savary type) passed over a guide wire and through-the-scope balloons for the dilation of peptic esophageal strictures in a randomized study. Thirty-four patients, 17 in each treatment arm, were studied. At entry, dysphagia was assessed according to a six point scale (0, unable to swallow; 5, normal). The end-point for dilation was to size 45F or 15 mm. Discomfort during the procedure was graded on a four-point scale (0, no discomfort; 1, mild; 2, moderate; 3, severe discomfort). Follow-up visits were at 1 week, 1 month, 3 months, and every 3 months thereafter for 2 years. At the 1-week visit, the size of esophageal lumen was measured by 8-, 10-, and 12-mm pills. Both devices effectively relieved dysphagia. By life-table analysis, stricture recurrence during the first year of follow-up was similar in both groups, but during the second year, the risk of recurrence was significantly lower in patients whose strictures were dilated with balloons. Other advantages of balloons included the need for fewer treatment sessions to achieve the defined end-diameter for dilation (1.1 + 0.1 versus 1.7 + 0.2, p < .05), and less procedural discomfort (p < .05). The differences in luminal size after dilation, measured by the barium pill test, were not significant. Ability to pass the 12-mm pill and absence of dysphagia were correlated. Our results indicate that both devices are effective in relieving dysphagia, but balloons may have a long-term advantage. PMID- 7789676 TI - Corrosive esophageal strictures: predictors of response to endoscopic dilation. AB - Twenty-one patients with corrosive esophageal strictures underwent contrast enhanced CT of the chest to determine (1) the esophageal wall thickness at the stricture site and (2) its correlation with number of sessions required for adequate dilation. Average esophageal wall thickness was defined as the mean thickness of all four walls at the site of the stricture, whereas the size of the thickest wall was taken as maximal esophageal wall thickness. Average esophageal wall thickness (8.52 +/- 0.61 mm; range, 5.4 to 13.5 mm) and maximal esophageal wall thickness (11.63 +/- 0.83 mm; range, 5.4 to 20 mm) were significantly higher in patients with corrosive esophageal strictures than normal esophageal wall thickness (2.70 +/- 0.04 mm, p < .01). These patients required a mean of 5.70 +/- 1.42 sessions for achieving adequate dilation. Age, sex, grade of dysphagia, and cause and site of the stricture did not influence the number of sessions required for adequate dilation. On multivariate analysis, maximal esophageal wall thickness (p < .01) but not average esophageal wall thickness or stricture length was independently associated with the number of sessions required for adequate dilation. Patients with maximal esophageal wall thickness of 9 mm or more required a significantly higher number of sessions for adequate dilation than did those with wall thickness of less than 9 mm (7.57 +/- 1.80 versus 1.42 +/- 0.27, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789677 TI - Randomized, prospective study of cyanoacrylate injection, sclerotherapy, or rubber band ligation for endoscopic hemostasis of bleeding canine gastric varices. AB - The purpose of this randomized, nonblinded study was to compare the effectiveness, safety, and technical ease of three different endoscopic techniques for the treatment of bleeding gastric varices in a canine model. Twenty dogs with large, bleeding gastric varices underwent endoscopic hemostasis with rubber band ligation, sclerotherapy, and cyanoacrylate injection. The time and number of attempts required to achieve definitive hemostasis were evaluated for each technique, and each method was assessed for ease of use. Ulceration rates, ulcer size and depth, and stigmata of ulcer hemorrhage were assessed at 1 week. Intravariceal sclerotherapy was the fastest and easiest to perform. Rubber band ligation was intermediate in technical ease, but it caused the largest and deepest ulcers and had the highest rates of stigmata of ulcer hemorrhage and secondary bleeding. Cyanoacrylate injection was the most cumbersome endoscopic method to perform. All three treatments were effective for controlling gastric variceal bleeding. Intravariceal sclerotherapy had the most favorable results overall because of its technical ease, efficacy, and modest complication rates. PMID- 7789678 TI - Randomized, controlled study of various agents for endoscopic injection sclerotherapy of bleeding canine gastric varices. AB - The purpose of this study was to compare the relative efficacy and technical ease of use of eight different agents for endoscopic hemostasis and obliteration of bleeding gastric varices in a canine model, as no comparative data are available on gastric variceal sclerotherapy. Large bleeding gastric varices in 20 heparinized dogs were randomized to endoscopic injection treatment with one of the following agents: cyanoacrylate; a 1:1:1 mixture of sodium tetradecyl sulfate 3%, ethanol 98%, and normal saline solution; ethanolamine oleate 5%; sodium morrhuate 5%; sodium tetradecyl sulfate 1.5%; polidocanol 1%; normal saline solution with epinephrine 1:10,000; or normal saline solution (control). The number and volume of injections and the time required to achieve complete hemostasis were evaluated; follow-up endoscopy was performed at 1 month to assess gastric variceal obliteration. Cyanoacrylate was the best agent overall in terms of immediate efficacy, low volume requirement, time required for initial hemostasis, and reduction of gastric variceal size. Cyanoacrylate, tetradecyl sulfate, and polidocanol were the most effective agents for reducing gastric variceal size. Epinephrine was effective for controlling induced or secondary bleeding caused by puncture of the gastric varices with the sclerotherapy needle during intravariceal injections. Ongoing studies are evaluating combinations of agents with different mechanisms of action, such as epinephrine (for vasoconstriction to minimize secondary bleeding) plus alcohol, and/or tetradecyl sulfate (for variceal thrombosis and sclerosis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789680 TI - Infrared video imaging of subsurface vessels: a feasibility study for the endoscopic management of gastrointestinal bleeding. AB - The feasibility of infrared video imaging of subsurface vessels in the stomach was investigated both experimentally and in more detail using computer simulations of light propagation. Infrared video imaging was first attempted in several experimental situations. Images of a human arm illuminated with infrared light (wavelength > 700 nm) revealed subcutaneous venous structures not revealed by visible light (wavelength of 500 to 600 nm). An infrared-sensitive video endoscope was used to view both a human arm and normal stomach wall. Infrared illumination within the stomach enhanced only the larger subsurface vessels. Infrared transillumination of a rat skin flap window chamber allowed video recording of images during injection of an absorbing dye, indocyanine green, into the blood volume and showed that indocyanine green can enhance the contrast in infrared images of small vessels. Computer simulations of vessels of varying depths and sizes indicated successful detection was possible by infrared imaging. Computer simulations demonstrated that the shadow caused by an imaged subsurface vessel has two characteristics: (1) the central loss of reflectance, which indicates the size of the vessel, and (2) the full-width half-maximum of the reflectance loss, which indicates the depth of the vessel. The simulations further suggested that images of small vessels can be dramatically enhanced (68 fold) by indocyanine green, which attenuates the transmittance of scattered light from behind the vessels to the surface for observation. On the other hand, indocyanine green enhances the contrast of large vessels to a lesser degree (2.6 fold). The ultimate goal is to develop an endoscopic video imaging system capable of capturing reflected light from the stomach wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789679 TI - Evaluation of the effects of esophageal varicosclerosants on local vascular occlusion and systemic blood coagulation. AB - The efficacy and safety of the various sclerosants available for esophageal sclerotherapy have not been adequately investigated. In the present study, we experimentally evaluated the effects on local vascular occlusion and systemic blood coagulation of five sclerosants: 5% ethanolamine oleate, 99.5% ethanol, 2% aethoxysclerol, thrombin, and n-butyl-2-cyanoacrylate. The effects were tested after injection into the auricular vein of rabbits. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen level, and peripheral blood platelet count were measured before injection and 5 minutes, 1 hour, 1 day, and 7 days later. Histologic examinations were then made of the auricular vein, lungs, liver, spleen, and kidneys. In the initial period after injection of ethanol or thrombin, fibrinogen level and platelet count were significantly reduced. Except for thrombin, none of the drugs affected prothrombin time or partial thromboplastin time. Local thrombosis took place after the injection of ethanolamine oleate, ethanol, and aethoxysclerol, whereas thrombin injection did not result in local thrombosis or vascular occlusion. Cyanoacrylate produced no local thrombus formation but caused vascular occlusion. Over-dosing of thrombin and ethanol led to sudden death of animals. These findings suggest that it is necessary to assess further the safety of intravascular use of thrombin, that the other drugs seem to be usable, and that careful consideration should be given to the excess use of ethanol in clinical settings. The present animal model may be useful for evaluating various sclerosants, although findings may not be applicable to humans because of differences in vascular size. PMID- 7789681 TI - Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract. PMID- 7789683 TI - Simulated sphincterotomy in a pig model. PMID- 7789684 TI - Determining required stent length in endoscopic retrograde biliary stenting. PMID- 7789682 TI - The feasibility of three-dimensional endoscopic ultrasonography: a preliminary report. PMID- 7789685 TI - A sphincterotome with variable-length wire for easier endoscopic sphincterotomy and quicker biliary drainage. PMID- 7789686 TI - A tapered balloon with hydrophilic coating to dilate difficult hilar biliary strictures. PMID- 7789687 TI - Esophageal squamous papilloma associated with adenocarcinoma. PMID- 7789690 TI - Endoscopic features of mucosa-associated lymphoid tissue lymphoma of the duodenum. PMID- 7789689 TI - Malacoplakia of the colon. PMID- 7789691 TI - Ventricular asystole during upper gastrointestinal endoscopic electrocoagulation. PMID- 7789692 TI - Definitions, diagnoses, and documentation. PMID- 7789688 TI - Lymphangioma of the colon diagnosed with an endoscopic ultrasound probe and dynamic CT. PMID- 7789693 TI - Endoscopic therapy of bleeding varices: do studies in animal models give us the answers we need? PMID- 7789694 TI - Periodic exchange of biliary stents. PMID- 7789695 TI - Guillotining the polypectomy snare: a proposed method for avoiding this complication. PMID- 7789696 TI - Acute suppuration of the pancreatic duct. PMID- 7789697 TI - Infrared transillumination gastroscopy. PMID- 7789698 TI - Percutaneous cholecystolithotomy: is gall stone recurrence inevitable? PMID- 7789699 TI - Endosonographically guided fine-needle aspiration puncture of paraesophagogastric mass lesions: preliminary results. PMID- 7789700 TI - [Risk, odds and significance--from the jungle book of medical statistics]. PMID- 7789701 TI - [Sterility--a women's issue?]. PMID- 7789702 TI - [The burnout syndrome. Etiology, possibilities for detection and help for prevention]. PMID- 7789703 TI - [Obstetrical management of prolonged pregnancy]. PMID- 7789704 TI - [Age specific and age corrected mortality in gynecological carcinoma--including breast carcinoma]. AB - Quality of life and life span are parameters which characterise a successful tumour diagnosis and therapy. We found out that the age-specific death rate and standardised death rate concerning gynaecological cancers and carcinoma of the breast in Bavaria increased and we compared different years. The standardized mortality ratio increased between 1977 and 1990 from 91 to about 108% Neither diagnostics using update equipment nor an individualised therapy improved the situation. The slightly increasing incidence rate does not explain the present rate of deaths in cancer. An important factor is the younger age and the endocrine situation of women at the time of the primary disease. 50% of our patients are less than 55 years old and pre- or perimenopausal. Estrogen-gestagen combinations used in contraceptives and hormone replacement therapy (HRS) seem to have a stimulating effect (Henderson). The significant decrease in cervical cancer is encouraging, but does not compensate the increase in breast cancer. No significant change is seen in ovarian cancer. PMID- 7789705 TI - [Multivariate analysis of clinico-pathologic predictors of axillary lymph node metastasis in invasive breast carcinoma]. AB - The aim of this study was to find both predictors of axillary lymph node involvement and predictors of level II or III involvement. With these predictors patients should be selected who can be spared axillary lymph node dissection or who qualify for removal of only first-level lymph nodes. 239 consecutive patients with invasive breast cancer stage I-III treated with total axillary dissection were evaluated. In multiple logistic regression analysis 17 clinical and histopathological variables were included. We found 4 multivariate significant predictors for metastatic axillary involvement: Clinically positive axilla, peritumoural lymphatic vessel invasion, multicentric or multifocal tumours and a large number of past pregnancies. Multivariate significant predictors of involvement of level II or III were peritumoural lymphatic vessel invasion, younger age, larger tumour size, multicentric or multifocal tumours and postmenopausal patient. The metastatic involvement of more than 3 nodes was associated with young age and clinically positive axilla. With these easily available predictors a reliable assessment of risk of metastatic involvement of the upper levels of the axillary nodes could be defined. The binary logistic regression model to axillary node involvement had a rather unsatisfactory predictive value. CONCLUSIONS: The risk calculation of level II or III involvement with these predictors may help the surgeon to find the adequate extent of axillary clearance needed in the individual patient. Multiparity proved to be an independent predictor of metastatic axillary node involvement. PMID- 7789706 TI - [Prognostic differentiation of ovarian carcinomas by immunohistochemical analysis of estrogen receptor expression]. AB - Analogous to breast cancer, the expression of estrogen receptors (ER) by human ovarian cancers is thought to be of prognostic significance. This prospective study was designed to evaluate the ability of immunohistochemistry (IHC) for ER to define prognostic subgroups in this disease and to possible characterize the group of patients that would benefit from ER analysis. The IHC technique for localising ER was published by Press and Green (1984). In IHC the percentage of cells stained was determined as well as the staining intensity that was graded on a 4 step scale. Tissue from the primary focus of 61 ovarian cancers was sampled during surgery and frozen immediately. FIGO Stage 1 disease was observed in 7 patients, stage 2 in 2, stage 3 in 36 and stage 4 in 16 women. Tumours of histological grade 1 were found in 3 cases, grade 2 in 20 and grade 3 in 38 specimen. Serous carcinoma was diagnosed in 43 lesions, mixed cell types in 10, mucinous and endometrioid each in 4. Minimal follow-up was 8 years. Statistical analysis was performed using the Wilcoxon Rank and Log-Rank test of Kaplan Meier curves. The median survival was 10.62 +/- 1.83 years for stage 1, 5.83 +/- 0.39 years for stage 2, 2.38 +/- 0.39 years for stage 3, and 3.71 +/- 0.76 years for stage 4. Tumour stage (p < 0.05), grade (p < 0.05) and cell type (p < 0.01) were predictors of survival. Age was of borderline significance (p = 0.058). The relative amount of stained cells was no predictor of prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789708 TI - [Immune reactions and survival of patients with ovarian carcinomas after administration of 131I-F(Ab)2 fragments of the OC 125 monoclonal antibody]. AB - The activation of the idiotypic network seems to be a beneficial approach to the immunological therapy of ovarian cancer. In a retrospective study 62 patients with ovarian carcinoma (of which 57 could be evaluated) received 1 mg of 131J F(Ab)2 OC 125 MAb one to five times after radical surgery and polychemotherapy. In twenty-eight patients (49%) a remarkable anti-idiotypic antibody (Ab2) response arose. The anti-idiotypic antibody (Ab2) plasma levels increased with increasing number of F(Ab)2 OC 125 MAb applications. The twenty patients (35%) who developed Ab2-concentrations > 10,000 U/ml had a significantly higher survival rate than the patients who showed weak (Ab2-concentrations < 10,000 U/ml) or no immunological response to 131J-F(Ab)2 OC 125 MAb treatment (p < 0.05). PMID- 7789707 TI - [Value of the TAG-72 (CA 72-4) tumor marker in primary diagnosis of ovarian carcinoma. A comparison with the established CA-125 marker]. AB - The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone. PMID- 7789709 TI - [Monitoring umbilical cord puncture and intravascular transfusions with Doppler ultrasound]. AB - Complications of percutaneous umbilical blood samplings and intravascular transfusions can be detected rapidly, easily and efficiently by Doppler ultrasound and therefore the operator can react as early as possible. In addition to real-time sonography Doppler ultrasound allows for assessment of haemodynamical changes due to intravascular transfusions both on the venous and arterial side of umbilical perfusion. Because of immediate recognition of bradycardia and other fetal cardiac frequency alterations as well as increase of resistance to blood flow on the arterial side the operator can react promptly. On the venous side correct application of transfused volume is monitored continuously by changes of flow velocity waveforms during injection and allows to assess dislocation of the needle. PMID- 7789710 TI - [Doppler echocardiographic analysis of blood flow through the fetal aorta and pulmonary valve in the second half of pregnancy]. AB - Pulsed Doppler velocimetry of the fetal aortic and pulmonary valves derived in the five-chamber-view and short-axis view were performed in 88 uncomplicated pregnancies between the 20th and 40th week of gestation. The maximal and mean velocities were assessed for both semilunar valves. Considering the valve diameters and heart rate the stroke volume and cardiac output for both ventricles were calculated. Furthermore, the common stroke volume, common cardiac output and the ratio of right to left cardiac output were calculated. Normal ranges for all these parameters were constructed and correlated with gestational age. The maximal velocities were higher in the aorta than in the pulmonary trunk, but no differences were found in the mean velocities. The stroke volume and cardiac output of the right ventricle were in higher ratio 1.3:1 than that of the left ventricle as an expression of the right ventricular dominance in the fetus. Intracardiac Doppler flow velocimetry gives an insight into the physiology of fetal circulation and is a basis for the analysis of blood flow under pathological conditions. PMID- 7789711 TI - [Prenatal management of fetofetal transfusion syndrome]. AB - The twin-twin transfusion syndrome is a rare but severe complication in monozygotic twins. A total of 172 twin pregnancies were investigated in our hospital between January 1990 and August 1993. The patients were divided into 4 groups: Group I: Normal twin pregnancy, treatment only in our hospital. Group II: Twin-twin transfusion syndrome, treatment only in our hospital. Group III: Normal twin pregnancy, delivery in another hospital. Group IV: Twin-twin transfusion syndrome, after treatment and therapy delivery in another hospital. These cases were analysed concerning prenatal management and perinatal outcome. The perinatal mortality rate in group I-IV was 17%, 58%, 18% and 60%, respectively. A benefit of aggressive amniocentesis in case of polyhydramnios, administration of digoxin and timing of labour could be demonstrated. PMID- 7789712 TI - [Preventive anti-D after massive fetomaternal hemorrhage]. AB - In the 36th week of gestation intrauterine death of both twins occurred in a 31 year old primigravida. The examination of the C- and the D-antigen of the mother's blood (result of previous testing: AB Rhesus negative) immediately before delivery showed a mixed field agglutination which pointed to a fetomaternal macrotransfusion. Fetal haemoglobin in the mother's circulation was 7.8% of her total haemoglobin, so that a fetomaternal haemorrhage of about 440 ml whole blood had to be suspected. For Rhesus-prophylaxis 17 standard doses of anti D-immunoglobulin were administered intramuscularly distributed over 4 days. No adverse effects were seen; fetal haemoglobin dropped to 2.0% 5 days and to 0.1% 15 days after the beginning of the treatment. A control examination after 9 months showed no signs of a Rhesus-(D)-sensitisation of the patient. PMID- 7789713 TI - [Psammoma bodies in cytological vaginal smears in metastatic ovarian carcinoma]. AB - The case of a 37-year old patient with ovarian cancer stage FIGO IV and vaginal metastasis is reported. The vaginal smear showed psammoma bodies, which are rarely found. The value of the diagnosis "psammoma bodies" is discussed, via a review of the literature. PMID- 7789714 TI - [Vaginal hemorrhage after hysterectomy]. AB - We report on two cases of vaginal bleeding after hysterectomy. These patients suffered from cyclical therapy resistant vaginal bleeding and complaint in the lower abdomen. The final diagnosis and therapy of a vaginal cuff endometriosis made it possible to eliminate the persistent clinical symptoms. These cases show the need for a discussion on the necessity of a special operative procedure in case of endometriosis genitalis interna and externa. PMID- 7789715 TI - [An unusual case: vaginal foreign body (forceps) as an incidental finding during primary operation for breast cancer]. AB - A 29 year-old patient was admitted for surgery because of two breast lumps. One of these was suspicious for malignancy by a mammogram and palpation. When her history was taken, the patient mentioned putrid vaginal discharge and denied any previous gynaecologic examination. After initial hesitancy, the patient agreed to have a pelvic examination. This revealed an oxydized iron rod protruding 2 cm out of the vagina. The object was identified by x-ray examination as one handle of iron forceps often used for cutting metal wires. The patient had been carrying this foreign body for fifteen years. She was not willing to relate any information about the cause of the manipulation or any eventual culprit. She was consistent and her personality was dominated by introverted behaviour. The foreign body was removed under the same anaesthesia as that used for the operation on the breast cancer. PMID- 7789716 TI - Dermatan sulfate as a potential therapeutic agent. AB - 1. Dermatan sulfate is a linear, sulfated polysaccharide and is a glycosaminoglycan component of several important proteoglycans. This minireview discusses the biosynthesis, structure and biological function of dermatan sulfate proteoglycans. 2. Dermatan sulfate and its derivatives are being investigated as a new class of anticoagulant and antithrombotic agents. 3. The preparation, chemistry and structure-activity relationship of dermatan sulfate is described. 4. Dermatan sulfate, low molecular weight dermatan sulfate and glycosaminoglycan mixtures containing dermatan sulfate have been used clinically. 5. The future prospects of these agents and other new, potentially useful dermatan sulfate based therapeutics are discussed. PMID- 7789717 TI - The in vivo and in vitro protective properties of taurine. AB - 1. Taurine is a ubiquitous, free amino acid found in mammalian systems. 2. The biological functions of taurine are unclear. 3. Various in vivo data suggest that taurine has a variety of protective functions and deficiency leads to pathological changes. 4. Depletion in rats of taurine increases susceptibility to liver damage from carbon tetrachloride. 5. Susceptibility to a variety of hepatotoxicants correlates with the estimated hepatic taurine level. 6. In vitro data suggest that taurine can protect cells against toxic damage. 7. Taurine protects isolated hepatocytes against carbon tetrachloride, hydrazine and 1,4 naphthoquinone but not against allyl alcohol, alpha-naphthylisothiocyanate (ANIT) or diaminodiphenyl methane (DAPM) cytotoxicity. 8. The mechanisms of protection are unclear but may include modulation of calcium levels, osmoregulation and membrane stabilization. PMID- 7789718 TI - Aspects of the thromboxane receptor system. AB - 1. The aim of this review is to establish what is known about the thromboxane (TP) receptor, and to identify where future research is headed. In addition, the impact of the recent advances at the molecular level on resolving pharmacological controversies, such as possible subtypes of the TP receptor, is discussed and what molecular information is known about the TP receptor presented. 2. The clinical status of TP receptor antagonists is considered particularly in relation to the potential role of epi prostaglandins. 3. Basic information about TP agonists, antagonists and signal transduction pathways is also given. PMID- 7789719 TI - Nitracrine and its congeners--an overview. AB - 1. An anticancer drug, nitracrine 1-nitro-9(3'3' dimethylaminopropylamino)acridine (Ledakrin, C-283) exhibits potent cytostatic effects which can be ascribed to interactions of the drug with DNA. 2. The reduction of the nitro group of nitracrine is one of the activation steps leading to the drug covalent binding to DNA and proteins both in subcellular systems and in the cell. 3. DNA-drug non-covalent interactions and covalent complexes are examined in several model systems and compared with the properties of a number of derivatives with programmed structural changes. 4. DNA-protein crosslinks and interstrand crosslinks are detected in the cells following exposition to the drug. 5. The drug exhibits selective toxicity and radiosensitization effects to hypoxic mammalian cells. PMID- 7789721 TI - Effects of chronic treatments with SM-9018, a potential atypical neuroleptic, on behavioral dopaminergic and serotonergic sensitivities in rats. AB - 1. Changes in behavioral dopaminergic and serotonergic sensitivities were studied in rats after withdrawal of the chronic treatments with SM-9018 (0.1 mg/kg/day), a potential atypical neuroleptic, and with haloperidol (0.3 mg/kg/day) using continuous infusion pumps. 2. Administration of SM-9018 inhibited the rat locomotor activities to an extent similar to that of haloperidol during the course of the 2 weeks treatment. 3. The incidence of the apomorphine-induced stereotyped behaviors (e.g., sniffing, chewing, licking and biting) was negligibly affected by SM-9018 treatment, but was markedly enhanced by haloperidol treatment. 4. The incidence of the 5-hydroxytryptophan-induced wet dog shakes and 8-hydroxy-2-(di-n-propyl-amino)tetralin-induced flat body posture was unaffected by either treatment with SM-9018 or haloperidol. 5. These findings suggest that SM-9018 is weaker than haloperidol in inducing the behavioral dopaminergic hypersensitivity after its chronic treatment and has a lower propensity to cause tardive dyskinesia. PMID- 7789723 TI - Taurine-induced hyperpolarizing shift of the reversal potential of the fast Na+ current in embryonic chick cardiomyocytes. AB - 1. Effects of taurine on the reversal potential of Na+ channel (INa) in isolated 17-day-old embryonic chick ventricular cardiomyocytes were examined using whole cell voltage clamp technique. Experiments were performed at room temperature (22 degrees C). 2. Test pulses were applied between -60 and +50 mV from a holding potential of -90 mV. Addition of taurine (1-20 mM) to the bath solution inhibited the INa at -30 mV in a concentration-dependent manner; by 38.8 +/- 3.7% (n = 14, P < 0.01) at 10 mM and by 49.5 +/- 4.6% (n = 12, P < 0.001) at 20 mM. 3. Simultaneously, the reversal potential was shifted in the hyperpolarizing direction by 10.6 +/- 2.9 mV (n = 10, P < 0.05) at 10 mM and by 12.6 +/- 2.2 mV (n = 9, P < 0.01) at 20 mM. The shift was also produced concentration dependently. Even when taurine at low concentrations (1 and 5 mM) enhanced INa, the shift occurred. 4. Intracellular taurine level decreased in Langendorff perfused guinea-pig hearts with Ca(2+)- and Mg(2+)-free solution, but not with Ca(2+)-free and 20 mM Mg2+ solution. 5. These results indicate that taurine shifts the reversal potential of the INa due to Na(+)-taurine cotransport, which might play an important role for the cell functions. PMID- 7789722 TI - Inhibitory action of SKPYMRFamide on acetylcholine receptors of Helix aspersa neurons: role of second messengers. AB - 1. SKPYMRFamide, a novel FMRFamide-like endogenous peptide reversibly decreases excitatory responses (depolarization and inward current) evoked by local ionophoretic application of acetylcholine (ACh) onto the soma of identified neurons F1, F2, F4 and F5/6 of the land snail, Helix aspersa. 2. Threshold concentrations of SKPYMRFamide for an inhibitory action on ACh-induced responses are 0.5-1 mumoll-1. This modulatory action of peptide is dose- and time dependent. 3. It is concluded that SKPYMRFamide inhibits ACh receptors through activation of specific binding sites on the plasma membrane. 4. The possible role of different second messengers in the modulatory influence of SKPYMRFamide on ACh receptors was tested using 13 modulators of different second messenger systems. 5. The results indicate that SKPYMRFamide may inhibit ACh receptors through activation of one or more of the following systems: phospholipases C, A2, NO synthase, soluble guanylate cyclase and lipoxygenases which elevate basal intracellulal levels of NO, cGMP, arachidonic acid, acyclic eicosanoids, inositol 1,4,5-trisphosphate (I(1,4,5)P3), I(1,4,5)P3-dependent Ca(2+)-mobilization followed by activation of calmodulin and Ca2+/calmodulin-dependent protein kinase II. Protein kinases A, C and cyclic eicosanoids do not appear to participate in modulatory action of SKPYMRFamide. PMID- 7789720 TI - Dietary ginsenosides improve endothelium-dependent relaxation in the thoracic aorta of hypercholesterolemic rabbit. AB - 1. Endothelium-dependent relaxation to acetylcholine was impaired in aortic rings from cholesterol-fed rabbits as compared to rabbits fed with a control diet. 2. The dietary treatment of rabbits with ginsenosides did not affect endothelium dependent relaxation to acetylcholine but did effect the relaxation in cholesterol-fed rabbits. 3. Dietary treatment of rabbits with ginsenosides did not alter the relaxations to sodium nitroprusside and the contractions to norepinephrine in rings without endothelium from both control and cholesterol-fed rabbits. 4. Ginsenoside feeding had no significant effect on the plasma lipid levels in both control and cholesterol-fed rabbits. 5. These results suggest that dietary supplementation of rabbits with ginsenosides improve the endothelium dependent relaxation to acetylcholine in the aortic blood vessels in cholesterol fed rabbits. This beneficial effect of ginsenosides feeding cannot be explained by a facilitation of the cyclic GMP effector pathway in the smooth muscle or by an enhanced cholesterol metabolism but may involve an increased production of nitric oxide by endothelial cells. PMID- 7789724 TI - Chronic effects of azidothymidine and acyclovir on pregnant rats. AB - 1. The antiviral effect of azidothymidine (AZT) can be potentiated by acyclovir (ACV), and this drug association has been used in the management of HIV-infected patients. In the present study we examined the effects of such an association on rat pregnancy. 2. AZT (60 mg/kg b.w.) and ACV (60 mg/kg b.w.) were given to groups of pregnant rats once a day from the 1st to the 20th day of gestation. 3. Maternal body weight gain was severely affected by ACV; this effect was attenuated in rats treated with AZT+ACV and was virtually absent with AZT alone. 4. The abortive action of ACV was markedly diminished in the group treated with the association AZT+ACV. 5. The deleterious effects of ACV on rat pregnancy are presumably due to its extraplacental actions, and these are, at least in part, counteracted by concomitant treatment with AZT. PMID- 7789726 TI - Effect of nifedipine treatment (imprinting) of rat feti and newborns on the responsiveness of adult rat's uterus. Extension of the imprinting theory. AB - 1. The uterus of adult progeny of rats treated with nifedipine during the late phase of pregnancy react in vitro to oxytocin less and the contractility of ones treated with higher dose (100 micrograms) disappears. 2. There is a more pronounced deficiency or lack of responsiveness in five week old animals treated with nifedipine neonatally. 3. The experiments demonstrate that perinatal imprinting can be developed not only on hormone receptors and enzymes but on ion (Ca2+) channels of the plasma membrane. Consideration of this fact might have an importance in clinical aspects too. PMID- 7789725 TI - Effects of alpha,beta-unsaturated sulphones and phosphonium salts on ecto-ATPase activity and contractile responses mediated via P2 chi-purinoceptors. AB - 1. In the guinea-pig urinary bladder and vas deferens, several alpha,beta unsaturated sulphones and phosphonium salts that were tested inhibited ecto ATPase activity. The sulphones were more active in the bladder but the phosphonium salts were more effective in the vas deferens. 2. These compounds either potentiated or inhibited purinergic contractile responses in the guinea pig urinary bladder and vas deferens. 3. alpha,beta-Unsaturated sulphones and phosphonium salts represent a new promising class of compounds, capable of modulating purinergic neurotransmission. PMID- 7789727 TI - Effect of etofibrate on bile production in the normolipidemic rat. AB - 1. The effect of etofibrate, the ethandiol-1,2 diester of nicotinic and clofibric acids on bile production was studied in male rats that received a daily dose of 300 mg of etofibrate/kg body weight by stomach tube for 10 days and were compared with control rats receiving the medium. 2. The bile duct was cannulated, animals were intravenously given 1 microCi (4-14C)-cholesterol/100 b.w. and bile was collected at different intervals for a total of 4 hr. 3. Etofibrate treatment decreased plasma cholesterol and triglyceride concentrations and increased the bile flow. The cummulative amount of both bile volume and total bile radioactivity secreted increased linearly in all the animals; the respective slopes being higher in etofibrate treated rats than in controls. 4. The main labelled component found in the bile was always bile acids rather than cholesterol and the proportion of each of these compounds was similar in both groups. Neither was any difference between the groups found in the concentration of bile acids, cholesterol and phospholipids nor in the cholesterol/(bile+phospholipid) ratio. 5. Besides other factors, the present results indicate that an increase in bile flow and biliary cholesterol excretion in its free form and after its conversion into bile acids should contribute to the hypocholesterolemic effect of etofibrate. PMID- 7789728 TI - 5-HT receptors on identified Lymnaea neurones in culture: pharmacological characterization of 5-HT3 receptors. AB - 1. The selective agonist, 1-(m-chlorophenyl)-biguanide (m-CPBG) and antagonist, 3 tropanyl-3,5-dichlorobenzoate (MDL 72222) were used to characterize the 5-HT3 receptors in cultured identified neurones; the serotonin-containing cerebral giant cells (CGCs) and some follower neurones in the buccal ganglia of Lymnaea stagnalis. 2. 5-HT and its agonists were pressure ejected, while the 5-HT antagonists were bath applied. 3. Although m-CPBG evoked mostly depolarizing responses, hyperpolarizing responses were sometimes evoked. 4. At 10(-4) M, m CPBG failed to mimic the responses of 5-HT, but at a concentration higher, 10(-3) M, pressure-ejected m-CPBG mimicked most 5-HT responses. 5. The 5-HT2 antagonist ketanserin failed to block the m-CPBG-evoked responses, whilst partially blocking the 5-HT responses. 6. These results suggest the presence of 5-HT3 receptors similar to those found in mammalian neurones, and that multiple subtypes of these receptors may be present in Lymnaea neurones. PMID- 7789729 TI - Barium enhances the excitability of a motoneurone from the cockroach (Periplaneta americana). AB - 1. An isolated ganglion preparation was used to investigate the effects of barium ions (Ba2+) on excitability of the soma of the 'fast' coxal depressor motoneurone (Df) from the cockroach Periplaneta americana. 2. Under current-clamp, short (50 ms) depolarising pulses applied to the soma of Df elicited damped membrane oscillations in normal external solution. In the presence of 10 mM Ba2+, similar pulses produced all-or-none action potentials (n = 12). 3. Under voltage-clamp, addition of Ba2+ to the external solution suppressed the Ca-dependent K+ conductance (IC) in Df (n = 4). 4. Modulation of IC may offer a means of altering the excitability, and therefore output, of motoneurone Df. PMID- 7789730 TI - A non-invasive method for distinguishing central from peripheral nervous system effect of respiratory depressant drugs in conscious rats. AB - 1. A simple, non-invasive method for distinguishing the central from peripheral effects of respiratory depressant drugs was developed in conscious rats. 2. The procedure involves exposing rats for 5 min to an air mixture containing 8% CO2 (central stimulant) followed by an i.v. bolus injection of 300 micrograms/kg sodium cyanide (peripheral stimulant) and comparing the changes in minute volume and mean inspiratory flow (respiratory drive) before and after drug treatment. 3. The central depressant drugs morphine, xylazine, L-2-phenylisopropyladenosine (L PIA) and gamma-hydroxybutyric acid. (GHBA) inhibited the CO2-induced increase in minute volume and enhanced the sodium cyanide-induced increase in mean inspiratory flow. 4. Peripheral depression produced by carotid body denervation had no effect on the CO2-induced increase in minute volume and inhibited the sodium cyanide-induced increase in mean inspiratory flow. PMID- 7789731 TI - Effect of prostaglandins on tyrosylprotein sulfotransferase activity in rat submandibular salivary glands. AB - 1. Tyrosylprotein sulfotransferase (TPST) is a key enzyme in the processing of several secretory proteins, including those found in saliva. In this report, the effect of prostaglandins (PG) on TPST activity in submandibular salivary gland was investigated. 2. The results revealed that PGE2 exhibited TPST stimulatory activity with a 1.5-fold stimulation at 100 microM concentration and a half maximal stimulation at 50 microM. The PGE2 stimulation was accompanied by an increase in the affinity of TPST towards sulfate acceptor (Km 1.4 microM-->0.12 microM) with little change in Vmax. 3. The TPST activity was also stimulated by two other major prostaglandins of salivary glands, PGF2 alpha and 6-Keto-PGF 1 alpha, however to lesser extent, 22 and 23%, respectively. Arachidonic acid, an intermediate prostaglandin precursor, had no effect on TPST activity. 4. The results suggest that prostaglandins and in particular PGE2 may play a role in the regulation of TPST catalyzed secretory protein tyrosine sulfation in salivary glands. PMID- 7789732 TI - Role of T-type Ca2+ channel inhibitors in the pacemaker depolarization in rabbit sino-atrial nodal cells. AB - 1. Effects of T-type Ca2+ channel inhibitors, Ni2+ and tetramethrin, on the spontaneous action potentials in rabbit sino-atrial nodal cells were examined. 2. The firing rate of spontaneous activity was 201 +/- 11 beats/min (n = 18). Experiments were performed at 36 degrees C. 3. Ni2+ (10(-5) to 10(-4) M) and tetramethrin (10(-7) to 5 x 10(-5) M) caused a negative chronotropic effect. Both inhibitors did not affect the maximum diastolic potential, and slowed the rate of depolarization during the diastole. 4. In the presence of TTX (10(-7) M), both inhibitors caused a stronger negative chronotropic effect, and hyperpolarized the maximum diastolic potential. The maximum rate of depolarization was enhanced, and the action potential duration (at 50% repolarization) was prolonged. The action potential amplitude was unaffected. Ni2+ had more potent actions than tetramethrin. 5. T-type and other Ca2+ channel inhibitors affected only the late phase of pacemaker potential, resulting in a negative chronotropic effect. 6. These results indicate that T-type Ca2+ channel inhibitors (Ni2+ and tetramethrin) slow the pacemaker depolarization at the late phase (but not at the initial phase), resulting in a negative chronotropic effect in the sino-atrial nodal cells. PMID- 7789733 TI - Diazoxide blocks the morphine induced lengthening of action potential duration on guinea-pig papillary muscle. AB - 1. Intracellular microelectrodes were used to evaluate the possible involvement of potassium currents in the action potential prolongation induced by morphine. To this purpose we investigated the electrophysiological effect of morphine on the isolated guinea pig right ventricular papillary muscle in the presence of the potassium channel opener and inhibitor diazoxide and glibenclamide respectively. 2. Diazoxide (1 microM), which is devoid of effect on its own, blocks the lengthening of action potential duration (APD) induced by morphine (5 mM). 3. However, in the presence of glibenclamide (1 microM), morphine (5 mM) prolonged APD in approximately the same proportion as that observed when used alone. 4. These results suggest that diazoxide but not glibenclamide sensitive potassium channels could mediate the APD prolongation induced by morphine. PMID- 7789734 TI - The effects of veratridine and BDF 9148 on the action potentials and contractility of the rat right ventricle. AB - 1. The effects of veratridine, BDF 9148 and lignocaine on the action potentials and contractile force of the electrically-driven rat right ventricle have been determined. 2. Veratridine at 10(-7)-10(-6) M and BDF 9148 at 10(-7)-10(-5) M had no effect on the threshold potential or amplitude but prolonged the ventricular action potentials. 3. In contractility studies, veratridine at 10(-7)-10(-6) M augmented the cardiac stimulation responses and the augmenting effects with 3 x 10(-7) and 10(-6) M were greater at 2 than 4 Hz. In the presence of veratridine at 3 x 10(-6) M, the ventricle would not pace. 4. BDF 9148 at 10(-7)-10(-5) M augmented the cardiac stimulation responses and the augmenting effects with 10( 7) and 3 x 10(-7) M were greater at 2 than 4 Hz and the effect was maximal at 3 x 10(-7) M and submaximal at 10(-5) M. The effects of BDF 9148 at 10(-5) were not readily reversible. 5. Lignocaine at 10(-4) M had no effect on the ventricular action potential duration but decreased the threshold potential and amplitude and also reduced the cardiac stimulation force responses. In the presence of lignocaine, the augmenting effects of veratridine and BDF 9148 on ventricular force were reduced. 6. In summary this study has shown that BDF 9148 prolongs the action potential and augments the contractile force responses of the rat right ventricle by a lignocaine-sensitive mechanism. BDF 9148 or similar drugs may have potential as positive inotropes in the treatment of heart failure. PMID- 7789735 TI - Effects of different inotropes with antioxidant properties on acute regional myocardial ischemia in isolated rabbit hearts. AB - 1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium agonist Bay T 5006 were studied in comparison to Bay K 8644. 2. In isolated Langendorff-rabbit hearts perfused at constant pressure, acute regional ischemia (MI) was induced by coronary artery occlusion (CAO) and quantitated from epicardial NADH-fluorescence photography. Drugs were applied either before or after CAO (pre-treatment or treatment) to permit distinguishing the influence of functional and direct cytoprotective actions in the poorly collateralized rabbit hearts. 3. SOD did not affect left ventricular pressure (LVP) or coronary flow (CF) and reduced MI only if applied before CAO. LVP and CF were enhanced by LUT or AMR but not by AVR. MI was reduced to a similar extent in hearts treated with either drug. Cardioprotection by LUT was not improved by starting drug application before CAO. 4. Bay K 8644 reduced LVP and particularly CF, whereas Bay T 5006 did not affect functional parameters. MI was enlarged by Bay K 8644 and remained unaffected by treatment or pretreatment with Bay T 5006. 5. AMR, LUT and AVR possess antiischemic properties related to an improvement of myocardial perfusion. Although oxygen free radicals contribute to ischemic tissue injury, as shown by the cardioprotective effectiveness of SOD, antioxidant properties of the flavonoids LUT and AVR do not seem to be relevant for the antiischemic effects. Our findings also give no evidence for antioxidant properties of dihydropyridines relevant for cardioprotection. PMID- 7789736 TI - Lipid peroxidation and antioxidant enzyme activity in aspirin-treated rats. AB - 1. Malondialdehyde formation and antioxidant enzyme activity after oral or intraperitoneal treatment of rats with various doses of aspirin was studied. 2. Aspirin, orally, had no effect on spontaneous, Fe(II)- or Fe(II)/ascorbate induced malondialdehyde formation in liver homogenates; orally, ascorbate-induced malondialdehyde production was inhibited but only after 5-day treatment with 500 mg/kg aspirin; after intraperitoneal injection, the drug inhibited ascorbate- and Fe(II)/ascorbate-induced production of malondialdehyde. 3. Aspirin had no effect on malondialdehyde formation in erythrocytes, irrespective of the dose and route of drug administration. 4. Aspirin increased glutathione peroxidase activity in liver after 5-day treatment with an oral dose of 500 mg/kg and decreased enzyme activity in both liver and erythrocytes, 24 hr after a single injection of the same dose. 5. Aspirin, in vivo slightly affected lipid peroxidation and antioxidant enzyme activity. PMID- 7789739 TI - Different calcium dependencies of contractile activity of prostatic and epididymal portions of rat vas deferens. AB - 1. The effects of some organic calcium entry blockers and different concentrations of extracellular calcium on electrically-evoked contractions of isolated epididymal and prostatic portions of rat vas deferens were investigated. 2. Both epididymal and prostatic parts of rat vas deferens responded to single pulse or train electrical field stimulation, with twitch contractions of submaximal amplitude. 3. Verapamil showed a biphasic action on the contractions produced by single pulse electrical stimulation. In concentrations < 10(-5) M, it potentiated the responses of both portions, but at higher concentrations, the excitatory action was overcome by a concentration-dependent inhibitory effect. 4. Nifedipine reduced the amplitude of electrically-evoked contractions of both portions in a concentration-dependent manner. The ED50 of nifedipine was 3.6 x 10(-8) M and 2.1 x 10(-6) M in prostatic and epididymal portions, respectively. 5. Dantrolene sodium reduced the amplitude of electrically-evoked contractions of both portions in a concentration-dependent manner. The ED50 of dantrolene was 1.55 x 10(-4) M and 9.1 x 10(-4) M in prostatic and epididymal portions, respectively. 6. Reduction of Ca2+ concentration in medium reduced the amplitude of contractions of both portions significantly. This calcium dependence was more apparent in low frequencies of electrical stimulation. PMID- 7789738 TI - Studies on protective effect of Cyperus scariosus extract on acetaminophen and CCl4-induced hepatotoxicity. AB - 1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl4-induced hepatic damage. 2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%. 3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 +/- 68, 867 +/- 305 and 732 +/- 212 IU/l (n = 10) respectively, compared to respective control values of 202 +/- 36, 59 +/- 14 and 38 +/- 7. 4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP; GOT and GPT levels to 192 +/- 31, 63 +/- 9 and 35 +/- 8. 5. The hepatotoxic dose of CCl4 (1.5 ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 +/- 30, 493 +/- 102 and 357 +/- 109 IU/l (n = 10) respectively, compared to respective control values of 177 +/- 21, 106 +/- 15 and 47 +/- 12. 6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl4-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 +/- 30, 207 +/- 95 and 75 +/- 38, respectively. 7. The plant extract also prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789737 TI - 3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine elicits convulsant effects in mice. AB - 1. The behaviour and EEG effects of the dopamine and sigma (sigma) ligands (+) 3 (3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)3-PPP) were studied in mice. 2. (+) 3-PPP dose-dependently (60-100 mg/kg i.p.) produced behavioural and electrical tonic-clonic seizures. 3. The incidence of the tonic seizures elicited by 100 mg/kg of the drug was significantly (P < 0.05) prevented by spiperone (0.5 mg/kg i.p.) and haloperidol (0.5 mg/kg i.p.). 4. The results show an influence on the behavioural and electrical threshold of convulsions by (+) 3-PPP depending on a prevalent interference on dopamine receptors. PMID- 7789740 TI - Analgesic effect of two calcitonins and in vitro interaction with opioids. AB - 1. When the analgesic effect of salmon-calcitonin (S-CT) and of eel-calcitonin (E CT), as well as their influence on the morphine-analgesia were compared, no significant differences were found. 2. While on isolated tissues, E-CT induced a significant increase on the effect of bremazocine, [D-Pen2,D-Pen5]enkephalin and [Met5]enkephalin and no changes were observed on the effect of DAMGO, suggesting that E-CT increases the effects of opioids acting on delta or kappa receptors but not on mu receptors. 3. These findings corroborate the possibility of interactions between calcitonin and the opioid system. PMID- 7789741 TI - Renal failure during acute toxicity produced by tullidora ingestion (Karwinskia humboldtiana). AB - 1. Acute effects of Karwinskia humboldtiana (Kh) were studied in some renal functions and structural patterns of renal tissue. 2. Haemodynamic changes were observed with decrements of the glomerular filtration rate, renal plasma flow and filtration fraction during acute intoxication. 3. A marked increment in the fractional excretion of sodium was observed in the rats treated with tullidora fruits (Kh). 4. Cloudy swelling and hydropic degeneration was seen 72 hr after intoxication, mainly in the proximal convoluted tubules. PMID- 7789743 TI - Preliminary evidence of a synergistic alpha 1- and beta 1-adrenoceptor regulation of rat pineal hydroxyindole-O-methyltransferase. AB - The activity of serotonin N-acetyltransferase in the rat pineal is regulated through a synergistic action of norepinephrine on alpha 1- and beta 1 adrenoceptors. Rat pineal hydroxyindole-O-methyltransferase (HIOMT) activity is also responsive to the beta 1-adrenoceptor, while melatonin synthesis and indoleamine release in certain species is apparently under alpha 1-adrenoceptor control. The present study reports that the simultaneous administration of doxazosin (a selective alpha 1-adrenergic antagonist) and metoprolol (a selective beta 1-adrenergic antagonist) reduces peak HIOMT activity significantly more than either agent alone, indicating that rat pineal HIOMT is also subject to synergistic alpha 1- and beta 1-adrenergic regulation. The relationship between alpha 1-adrenoceptor stimulation, serotonin release, and HIOMT activity is considered, following the observation that nocturnal HIOMT activity is elevated in serotonin-depleted pineal glands. PMID- 7789742 TI - Ethane 1,2-dimethane sulfonate effects on the testis of the lizard, Podarcis s. sicula Raf: morphological and hormonal changes. AB - Ethane 1,2-dimethane sulfonate (EDS) destroys Leydig cells in the testis of some rodents (mice excluded), disrupts interstitial and germinal compartments in the frog, Rana esculenta, while it stimulates testicular activity in the teleost, Gobius paganellus. In the Japanese quail the toxin removes mature spermatozoa. There is no information on EDS effects in reptiles. The present study examines the effect of EDS treatment in the lizard Podarcis s. sicula Raf during two different periods of the testicular cycle (winter stasis and breeding season). Animals received a single EDS injection (100 mg/kg body wt) and were sacrificed at 0 and 24 hr and 3, 5, 7, 11, and 28 days after injection. Androgens were measured in plasma and right testes, while left testes were examined histologically. Plasma androgen levels decreased 5-7 days after EDS injection, alongside interstitial tissue destruction and mast cell appearance, with slight but significant increases on Days 11 and 28. Testicular androgen levels did not change. On Day 11 metaphases were present in the interstitial tissue which regenerated on Day 28. Between Days 5 and 7 some pycnotic nuclei of spermatocytes appeared, mitotic activity of spermatogonia was normal, but germ cell stages were disorganized and empty spaces appeared at the boundary of the tubule. These data show that a single EDS injection results in destruction and repopulation of the interstitial cells in a reptile. Moreover, the effects of EDS in the lizard suggest that P. s. sicula Raf testis responds to the toxin in a similar fashion to the rat testis. PMID- 7789744 TI - Gonadotropin-releasing activities of the three native forms of gonadotropin releasing hormone present in the brain of gilthead seabream, Sparus aurata. AB - Three forms of gonadotropin-releasing hormone (GnRH) have been recently identified in the brain of gilthead seabream (Sparus aurata): salmon GnRH (sGnRH), chicken GnRH-II (cGnRH-II), and a novel form, Ser8-mammalian GnRH, named seabream GnRH (sbGnRH). sbGnRH is the most abundant form in the pituitaries of sexually mature seabream during the spawning season. The present study investigated the gonadotropin-releasing activities of the three native forms of GnRH found in seabream brains, as well as of two structural analogs of sbGnRH. All native forms of GnRH stimulated gonadotropin-II (GtH-II) secretion in preovulatory female seabream. cGnRH-II was found to be 7 to 8 times more potent than sbGnRH and 2 times more potent than sGnRH in inducing GtH-II release. sGnRH was found to be 3.5 to 5 times more potent than sbGnRH in inducing GtH-II secretion. These data demonstrate that cGnRH-II, which is not present in pituitaries of sexually mature seabream, is the most potent GtH-II releaser, whereas sbGnRH, 500 times more abundant than sGnRH in the pituitary of maturing fish, is the least potent. The lower potency of sbGnRH may suggest faster enzymatic breakdown, more rapid clearance from the circulation, or a lower binding affinity to the pituitary GnRH receptor. The lower bioactivity of sbGnRH may be compensated for by its high levels in the pituitary. The two analogs of sbGnRH, [D-Nal(2)6,Pro9-NEt]-sbGnRH and [D-Arg6,Pro9-NEt]-sbGnRH, were equipotent to each other and 5 times more potent than sbGnRH in inducing GtH-II release in preovulatory seabream. However, they were 5 to 6 times less active than the analog of mammalian GnRH, [D-Ala6,Pro9-NEt]-mGnRH. Strategies for designing superactive analogs of sbGnRH are discussed. PMID- 7789745 TI - The occurrence and distribution of GnRH in the brain of Atlantic hagfish, an agnatha, determined by chromatography and immunocytochemistry. AB - In Atlantic hagfish (Myxine glutinosa), chromatographic and immunocytochemical evidence showed that the brain contains a gonadotropin-releasing hormone (GnRH) like molecule that is closely related to lamprey GnRH-III. The chromatographic studies (HPLC) used specific antisera directed against mammalian GnRH and lamprey GnRH-I. In addition to these antisera, other specific antisera were tested in immunocytochemical studies, including chicken GnRH-I, chicken-GnRH-II, salmon GnRH, and lamprey GnRH-III. Using a lamprey GnRH-I antiserum, an early eluting GnRH form coeluted on HPLC with lamprey GnRH-III standard and an unknown form coeluted with the chicken GnRH-II standard. Radioimmunoassay of brain tissue detected GnRH immunoreactivity only when the lamprey GnRH-I antibody was used. A GnRH-like immunoreactivity was also obtained immunocytochemically in the neurohypophysis with the use of antisera against chicken GnRH-II, salmon GnRH, lamprey GnRH-I, and lamprey GnRH-III. These studies indicate that, contrary to earlier reports, hagfish do have a GnRH-like molecule that is more closely related, in terms of immunological determinants, to lamprey GnRH-III than to other currently known vertebrate GnRH molecules. PMID- 7789746 TI - Effect of induced metamorphosis on the immune system of the axolotl, Ambystoma mexicanum. AB - Metamorphosis was induced in neotenic axolotls by immersion of the animals in a solution of thyroid hormone. Hematology of the axolotls was examined before, during, and after metamorphosis. There was a transient decrease in numbers of certain white blood cells during metamorphic climax and a permanent shift in the pattern of circulating cells. The eosinophilic granulocyte was the dominating leukocyte type in neotenes and in metamorphosing animals up to midclimax. Lymphocytes and neutrophilic granulocytes (polymorphs) significantly decreased during midclimax. In postmetamorphic axolotls, lymphocytes and polymorphs predominated. The observed decrease of some leukocytes in metamorphosing animals accords with a transient immunosuppression at metamorphic climax. Metamorphosed axolotls showed a humoral immune response (increase in circulating plasma cells) after repeated antigen challenge, whereas neotenic axolotls did not. Alterations in both cellular and humoral immunity are suggested to occur in both young and adult axolotls following experimental induction of metamorphosis. PMID- 7789747 TI - Effects of prolactin and fish pituitary extract on plasma calcium levels in common carp, Cyprinus carpio. AB - The effects of prolactin (PRL) from both mammalian and piscine sources on plasma calcium levels in common carp, Cyprinus carpio, were investigated. Injections of ovine prolactin (oPRL) or homologous fish pituitary extract or partially purified prolactin of murrel, Channa punctatus pituitary (mPRL), caused significant increases in total and ultrafiltrable plasma calcium. Larger hypercalcemic responses were observed in fish kept in high-calcium fresh water and normal tap water than in fish in low-calcium fresh water. Injections of oPRL caused dose dependent increases in plasma calcium level. The highest dose (1 mg/kg body wt) of oPRL had a reduced hypercalcemic effect. Administration of EGTA (200 microM/kg body wt) reduced the stimulatory effects of daily injections of oPRL or mPRL on plasma calcium in freshwater common carp under laboratory conditions. These results indicate that PRL may be involved in regulating plasma calcium levels in fish. PMID- 7789748 TI - Timed daily administrations of hormones and antagonists of neuroendocrine receptors alter day-night rhythms of allograft rejection in the gulf killifish, Fundulus grandis. AB - Immune activity during scale allograft rejection, measured by melanophore destruction, is two to three times greater at night (12-hr scotophases) than during the day (12-hr photophases) in gulf killifish (Fundulus grandis). In the present study of killifish, hormones and antagonists of neuroendocrine receptors were administered daily at 0800 or 2000 hr during either 12-hr photoperiods (light onset: 0800 hr) or continuous light to examine possible neuroendocrine regulation of the allograft rejection rhythm. Immune activity peaked 0-12 hr after the time of daily growth hormone injections (0800 or 2000 hr) in fish held under continuous light and examined twice daily (0800 and 2000 hr) for melanophore breakdown. Immune activity peaked 12-24 hr after the time of day when cortisol-supplemented meals were provided (light onset or light offset) whether fish were treated throughout the days of melanophore examinations or pretreated for 3 days only prior to melanophore examinations. Daily rhythms of immune activity were not observed in fish treated with propranolol or naloxone at light offset only, growth hormone or atropine at light onset only, or prolactin at either light onset or light offset; these timed-treatments also reduced (prolactin or growth hormone) or prolonged (propranolol or naloxone) the length of time needed to destroy all melanophores within an allograft compared with controls. These results demonstrate that neuroendocrine factors can modulate a daily rhythm of immune function in fish. PMID- 7789749 TI - Estrogen downregulation of albumin and a 170-kDa serum protein in the turtle, Trachemys scripta. AB - We examined changes in serum protein composition after estradiol-17 beta treatment of ovariectomized female Trachemys scripta, with the objective of identifying proteins that are repressed by estrogen. The experimental protocol was validated by measuring serum estradiol-17 beta levels with a specific radioimmunoassay. Control turtle sera contained little or no estradiol-17 beta (mean = 25.8 pg/ml) while estrogen-treated turtle sera had elevated estradiol-17 beta levels (mean = 333.3 pg/ml). Estrogen treatment resulted in a significant increase in serum protein concentration. The increase was due largely to a 213 kDa protein that was abundant in estrogen-treated animal sera but was low or absent in control animal sera. This protein was identified as vitellogenin based on its biochemical characteristics (molecular weight, elution profile from DEAE, precipitation in the presence of Mg2+/EDTA). Several proteins were decreased in the sera of estrogen-treated animals. One of these had a molecular weight of 66 kDa and was determined to be serum albumin. This protein crossreacted in Western blot analyses with polyclonal antisera against chicken and human serum albumins. Also, amino acid sequence analysis revealed substantial homology between the 66 kDa turtle protein and serum albumins from other vertebrate species. Another protein decreased by estrogen treatment had a molecular weight of 170 kDa. Both albumin and the 170-kDa protein were reduced in estrogen-treated turtles to levels about 50% of those present in control turtles. Using [35S]methionine labeling and denaturing (SDS) polyacrylamide gel electrophoresis, we detected the presence of newly labeled albumin and the 170-kDa protein in T. scripta liver cube cultures, indicating that these proteins are derived from the liver. Data from this study reveal that estrogen downregulates several serum proteins in T. scripta, while upregulating serum vitellogenin. The response to estrogen in this reptile is similar to that in the amphibian Xenopus laevis, suggesting that estrogen downregulation of serum proteins during vitellogenesis may be widespread among oviparous vertebrates. PMID- 7789751 TI - Serum steroid hormones and the reproductive cycle of the female bonnethead shark, Sphyrna tiburo. AB - The bonnethead shark Sphyrna tiburo reproduces by placental viviparity with one of the shortest gestation periods (4.5-5 months) known in sharks. In southwest Florida, mating in this species occurs in November, sperm is stored until ovulation/fertilization the following March-April, and parturition occurs in August. Serum concentrations of four steroid hormones (17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone) were determined by radioimmunoassay over a complete reproductive cycle in mature females from a wild population. Serum 17 beta-estradiol and testosterone levels are high during mating and preovulatory stages. Preovulatory concentrations of testosterone are greater in female S. tiburo than in any other female elasmobranch previously studied. Progesterone levels are significantly elevated during preovulatory, ovulatory, and postovulatory stages, while serum dihydrotestosterone levels increase significantly during the preovulatory stage. Our study is the first to demonstrate a sustained rise in progesterone during gestation in a placental shark and suggests a regulatory role for this hormone during the period prior to implantation of the embryos in the uterus. PMID- 7789750 TI - Gonadotropin releasing hormone stimulation of cyclic 3',5'-AMP in the pituitary cell of a teleost (Channa punctatus, Bloch) requires extracellular calcium: its relationship to gonadotropin release. AB - Pituitary cells were prepared by enzymatic dispersion and incubated in vitro. To observe the effect of gonadotropin releasing hormone (GnRH) and Ca2+ on the murrel pituitary cyclic 3',5'-AMP (cAMP), cells were dispersed by 0.3% collagenase plus 0.05% trypsin in Earle's minimum essential medium without Ca2+ and a considerably high yield of viable cells were obtained. Addition of a murrel, Channa punctatus, GnRH (cGnRH, 10 micrograms/incubation) to pituitary cell incubation (6 x 10(4) cells/well) containing 4 mM theophylline, a phosphodiesterase (PDE) inhibitor, stimulated cAMP accumulation in the pituitary cell 2.4-fold and its release into the medium about 2-fold as compared to control. The extent of stimulation was greatly increased on addition of Ca2+ (2 mM/incubation) with cGnRH: accumulation 5.8-fold and release 3.7-fold, respectively, in comparison to control. A time-course study with cGnRH (20 micrograms/incubation) plus Ca2+ (2 mM/incubation) on pituitary cell cAMP accumulation showed that the peak of cAMP level was reached at 15 min and remained at the same level until 60 min in the presence of theophylline; this peak was drastically reduced (5-fold) at 30 min in the absence of theophylline, indicating rapid hydrolysis of cAMP by PDE. Ca(2+)-augmented cGnRH stimulatory effect on cAMP accumulation and release could be significantly (P < 0.01) inhibited by verapamil (3 microM/incubation), a specific calcium channel blocker, suggesting requirement of extracellular Ca2+ influx in this process. Calmodulin (CaM), a Ca2+ carrier protein, addition to cGnRH and Ca2+ incubation further augmented the increase of cellular accumulation of cAMP and its release by 39.5 and 45%, respectively, in comparison to cGnRH and Ca2+ (both were statistically significant, P < 0.01). CaM effect could be blocked by calmidazolium (1 microM/incubation), a specific inhibitor of CaM, indicating specificity of the stimulatory action of CaM. Addition of radioiodinated 125I-CaM, in the presence of Ca2+ or cGnRH plus Ca2+ resulted in the binding of 125I-CaM to pituitary cells and to the pellet of the lysed cells. 125I-CaM specifically binds to pituitary cell plasma membrane preparation and saturation of 125I-CaM binding occurred at 9 ng of 125I-CaM. To investigate whether cGnRH plus Ca(2+)-stimulation of pituitary cells cAMP is linked to gonadotropin (GtH) release, similar protocols were followed. It was found that GtH release was augmented to 7-fold by cGnRH plus Ca2+, which was inhibited by verapamil and stimulated by CaM in a similar manner as observed in the case of cAMP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7789752 TI - Vicious circles: looking back on resistance plasmids. PMID- 7789753 TI - Involvement of the host initiator function dnaA in the replication of coliphage lambda. AB - We demonstrate that the initiation of coliphage lambda DNA replication is dependent on the host initiator function dnaA, provided that the lambdoid prophage Rac is absent. Presence of Rac compensated the absence of dnaA function, causing initiation of replication. In dnaAts rac+ cells at 43 degrees, most of parental phage DNA molecules, after one round of theta replication, switched to a replication with features of the sigma mode and produced progeny at high yield. Initiation of replication of the lambda Pts1 mutant at 43 degrees was blocked by dnaA function; however, under dnaA-rac+ conditions all parental phage DNA molecules, after one round of theta replication, switched to the sigma mode and produced progeny at high yield. Taking into account our recent finding that transcriptional activation of ori lambda seems to be dnaA-regulated (to be published elsewhere), we suggest that the DnaA-lambda Pts1 incompatibility occurs at the insertion of the ori lambda-bound lambda O-lambda P-DnaB preprimosome between the complementary lambda DNA strands. The role of Rac and the mechanism of the switch from theta to sigma mode of lambda phage DNA replication are discussed. PMID- 7789754 TI - The mechanism of recA polA lethality: suppression by RecA-independent recombination repair activated by the lexA(Def) mutation in Escherichia coli. AB - The mechanism of recA polA lethality in Escherichia coli has been studied. Complementation tests have indicated that both the 5'-->3' exonuclease and the polymerization activities of DNA polymerase I are essential for viability in the absence of RecA protein, whereas the viability and DNA replication of DNA polymerase I-defective cells depend on the recombinase activity of RecA. An alkaline sucrose gradient sedimentation analysis has indicated that RecA has only a minor role in Okazaki fragment processing. Double-strand break repair is proposed for the major role of RecA in the absence of DNA polymerase I. The lexA(Def)::Tn5 mutation has previously been shown to suppress the temperature sensitive growth of recA200(Ts) polA25::spc mutants. The lexA(Def) mutation can alleviate impaired DNA synthesis in the recA200(Ts) polA25::spc mutant cells at the restrictive temperature. recF+ is essential for this suppression pathway. recJ and recQ mutations have minor but significant adverse effects on the suppression. The recA200(Ts) allele in the recA200(Ts) polA25::spc lexA(Def) mutant can be replaced by delta recA, indicating that the lexA(Def)-induced suppression is RecA independent. lexA(Def) reduces the sensitivity of delta recA polA25::spc cells to UV damage by approximately 10(4)-fold. lexA(Def) also restores P1 transduction proficiency to the delta recA polA25::spc mutant to a level that is 7.3% of the recA+ wild type. These results suggest that lexA(Def) activates a RecA-independent, RecF-dependent recombination repair pathway that suppresses the defect in DNA replication in recA polA double mutants. PMID- 7789755 TI - Mutations affecting donor preference during mating type interconversion in Saccharomyces cerevisiae. AB - Homothallic strains of Saccharomyces cerevisiae can convert mating type from a to alpha or alpha to a as often as every generation, by replacing genetic information specifying one mating type at the expressor locus, MAT, with information specifying the opposite mating type. The cryptic mating type information that is copied and inserted at MAT is contained in either of two loci, HML or HMR. The particular locus selected as donor during mating type interconversion is regulated by the allele expressed at MAT. MATa cells usually select HML, and MAT alpha cells usually select HMR, a process referred to as donor preference. To identify factors required for donor preference, we isolated and characterized a number of mutants that frequently selected the nonpreferred donor locus during mating type interconversion. Many of these mutants were found to harbor chromosome rearrangements or mutations at MAT or HML that interfered with the switching process. However, one mutant carried a recessive allele of CHL1, a gene previously shown to be required for efficient chromosome segregation during mitosis. Homothallic strains of yeast containing a null allele of CHL1 exhibited almost random selection of the donor locus in a MATa background but were normal in their ability to select HMR in a MAT alpha background. Our results indicate that Chl1p participates in the process of donor selection and are consistent with a model in which Chl1p helps establish an intrinsic bias in donor preference. PMID- 7789756 TI - Meiotic chromosome pairing in triploid and tetraploid Saccharomyces cerevisiae. AB - Meiotic chromosome pairing in isogenic triploid and tetraploid strains of yeast and the consequences of polyploidy on meiotic chromosome segregation are studied. Synaptonemal complex formation at pachytene was found to be different in the triploid and in the tetraploid. In the triploid, triple-synapsis, that is, the connection of three homologues at a given site, is common. It can even extend all the way along the chromosomes. In the tetraploid, homologous chromosomes mostly come in pairs of synapsed bivalents. Multiple synapsis, that is, synapsis of more than two homologues in one and the same region, was virtually absent in the tetraploid. About five quadrivalents per cell occurred due to the switching of pairing partners. From the frequency of pairing partner switches it can be deduced that in most chromosomes synapsis is initiated primarily at one end, occasionally at both ends and rarely at an additional intercalary position. In contrast to a considerably reduced spore viability (approximately 40%) in the triploid, spore viability is only mildly affected in the tetraploid. The good spore viability is presumably due to the low frequency of quadrivalents and to the highly regular 2:2 segregation of the few quadrivalents that do occur. Occasionally, however, quadrivalents appear to be subject to 3:1 nondisjunction that leads to spore death in the second generation. PMID- 7789757 TI - Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis specific double-strand break formation in Saccharomyces cerevisiae. AB - A temperature-sensitive mre11-1 mutation of Saccharomyces cerevisiae causes defects in meiotic recombination and DNA repair during vegetative growth at a restrictive temperature. We cloned the MRE11 gene and found that it encodes a 643 amino acid protein with a highly acidic region containing a heptad repeat of Asp at its C-terminus and is located downstream of YMR44 near the RNA1 locus on the right arm of chromosome XIII. Transcripts of the MRE11 gene increased transiently and showed the same kinetics as that of the RAD50 gene during meiosis. In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished. A comparison of the properties of mre11::hisG and a rad50 deletion mutant (rad50 delta) indicated that both mutants exhibited similar phenotypes in both meiosis and mitosis. Characterization of two double mutants, mre11::hisG rad50 delta and mre11::hisG rad50S, showed that MRE11 and RAD50 belong to the same epistasis group with respect to meiotic DSB formation and mitotic DNA repair. Using a two-hybrid system, we found that Mre11 interacts with Rad50 and itself in vivo. These results suggest that Mre11 and Rad50 proteins work in a complex in DSB formation and DNA repair during vegetative growth. PMID- 7789759 TI - Some property of the nucleus determines the competence of Neurospora crassa for transformation. AB - In Neurospora, transformation of spheroplasts is quite efficient and usually occurs with the transforming DNA integrated at ectopic sites in the chromosome. However, only a small fraction of the spheroplasts is actually competent for transformation. To distinguish whether the limitation to competence is at the level of the plasma membrane or at the level of the nucleus, we performed experiments in which heterocaryotic spheroplasts were required to integrate two different plasmids in one transformation procedure. The cotransformants were then analyzed to determine into which nucleus or nuclei the separate plasmids had integrated. Results of such experiments confirm that successful ectopic transformation in Neurospora crassa requires a competent nucleus. The integration patterns of the two separate plasmids indicate that the availability of appropriate chromosomal sites for ectopic integration may be an aspect of nuclear competence. PMID- 7789758 TI - Ectopic integration of transforming DNA is rare among neurospora transformants selected for gene replacement. AB - In a variety of organisms, DNA-mediated transformation experiments commonly produce transformants with multiple copies of the transforming DNA, including both selected and unselected molecules. Such "cotransformants" are much more common than expected from the individual transformation frequencies, suggesting that subpopulations of cells, or nuclei, are particularly competent for transformation. We found that Neurospora crassa transformants selected for gene replacement at the am gene had not efficiently incorporated additional DNA, suggesting that nuclei that undergo transformation by homologous recombination are not highly competent at integration of DNA by illegitimate recombination. Spheroplasts were treated with DNA fragments homologous to am and with an Escherichia coli hph plasmid. Transformants were initially selected for hph (hygromycinR), allowed to conidiate to generate homokaryons and then selected for either Am- (gene replacements) or hph. Surprisingly, most am replacement strains were hygromycinS (124/140) and carried no extraneous DNA (116/140). Most transformants selected for hph also had ectopic copies of am DNA and/or multiple copies of hph sequences (32/35), generally at multiple sites, confirming that efficient cotransformation could occur. To test the implication that cotransformation involving gene replacement and ectopic integration is rare, we compared the yields of am replacement strains with or without prior selection for hph. The initial selection did not appreciably help (or hinder) recovery of strains with replacements. PMID- 7789760 TI - sli-1, a negative regulator of let-23-mediated signaling in C. elegans. AB - By screening for suppressors of hypomorphic mutations of let-23, a receptor tyrosine kinase necessary for vulval induction in Caenorhabditis elegans, we recovered > or = 12 mutations defining the sli-1 (suppressor of lineage defect) locus. sli-1 mutations suppress four of five phenotypes associated with hypomorphic alleles of let-23 but do not suppress let-23 null alleles. Thus, a sli-1 mutation does not bypass the requirement for functional let-23 but rather allows more potent LET-23-dependent signaling. Mutations at the sli-1 locus are otherwise silent with respect to vulval differentiation and cause only a low penetrance abnormal head phenotype. Mutations at sli-1 also suppress the vulval defects but not other defects associated with mutations of sem-5, whose product likely interacts with LET-23 protein during vulval induction. Mutations at sli-1 suppress lin-2, lin-7 and lin-10 mutations but only partially suppress lin-3 and let-60 mutations and do not suppress a lin-45 mutation. The sli-1 locus displays dosage sensitivity: severe reduction of function alleles of sli-1 are semidominant suppressors; a duplication of the sli-1(+) region enhances the vulvaless phenotype of hypomorphic mutations of let-23. We propose that sli-1 is a negative regulator that acts at or near the LET-23-mediated step of the vulval induction pathway. Our analysis suggests that let-23 can activate distinct signaling pathways in different tissues: one pathway is required for vulval induction; another pathway is involved in hermaphrodite fertility and is not regulated by sli-1. PMID- 7789761 TI - Genes that regulate both development and longevity in Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determination of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. PMID- 7789763 TI - P-element-induced male recombination can be produced in Drosophila melanogaster by combining end-deficient elements in trans. AB - Male recombination, not normally present in Drosophila melanogaster, can be produced at high rates when target P elements at homologous sites are combined in the presence of transposase protein. We have produced a set of elements by in situ deletion of a particular insertion and have found elements that have deletions stretching into either end. Elements were tested in pairs to see whether they complement each other in their ability to induce recombination. The combination of elements that are deficient for the same end produces very little recombination, but the combination of a right-end and a left-end element can generate recombination values higher than given by two complete P[CaSpeR] elements at homologous sites. This strongly suggests that "hybrid" P elements, containing ends from two different elements, can be recognized by transposase protein. We have also examined genotypes containing a normal and an end-deficient element and found that they yield reasonably high levels of recombination. We interpret the resultant gametes from such genotypes as showing that the majority of events in this genotype derive from the association of complementary ends from the same element, whereas the complementary ends from elements in trans associate in only a minority of cases. PMID- 7789762 TI - Horka, a dominant mutation of Drosophila, induces nondisjunction and, through paternal effect, chromosome loss and genetic mosaics. AB - Fs(3)Horka (Horka) was described as a dominant female-sterile mutation of Drosophila melanogaster. Genetic and cytological data show that Horka induces mostly equational nondisjunction during spermatogenesis but not chromosome loss and possesses a dominant paternal effect: the X, second, third and the fourth chromosomes, but not the Y, are rendered unstable while undergoing spermatogenesis and may be lost in the descending zygotes. The frequency of Horka induced chromosome loss is usually 2-4% but varies with the genetic background and can be over 20%. The X chromosome loss occurs during the gonomeric and the initial cleavage divisions. Loss of the X and fourth chromosomes shows no correlation. We propose, based on similarities in the mutant phenotypes with the chromosome destabilizing mutations nonclaret disjunctional and paternal loss, that the normal Horka+ product is required for function of the centromeres and/or nearby regions. Horka is a convenient tool for the generation of gynandromorphs, autosome mosaics and for the study of gene expression in mosaics. PMID- 7789764 TI - Hypomorphic mutations in the larval photokinesis A (lphA) gene have stage specific effects on visual system function in Drosophila melanogaster. AB - Of the many genes that are expressed in the visual system of Drosophila melanogaster adults, some affect larval vision. However, with the exception of one X-linked mutation, no genes that have larval-specific effects on visual system structure or function have previously been reported. We describe the isolation and characterization of two mutant alleles that define the larval photokinesis A (lphA) gene, one allele of which is associated with a P-element insertion at cytogenetic locus 8E1-10. Larvae that express lphA mutations are, like normal animals, negatively photokinetic, but they are less responsive to white light than lphA + controls. Larvae that are heterozygous in trans for a mutant lphA allele and a deficiency that uncovers the lphA locus are blind, which indicates that the mutant allele is hypomorphic. lphA larvae respond normally to odorants and taste stimuli. Moreover, the lphA mutations do not affect adult flies' fast phototaxis or visually driven aspects of male sexual behavior, and electroretinograms recorded from the compound eyes of lphA/deficiency heterozygotes and lphA1/lphA2 females are normal. These observations suggest that the lphA gene affects a larval-specific aspect of visual system function. PMID- 7789765 TI - A physical map of the X chromosome of Drosophila melanogaster: cosmid contigs and sequence tagged sites. AB - A physical map of the euchromatic X chromosome of Drosophila melanogaster has been constructed by assembling contiguous arrays of cosmids that were selected by screening a library with DNA isolated from microamplified chromosomal divisions. This map, consisting of 893 cosmids, covers approximately 64% of the euchromatic part of the chromosome. In addition, 568 sequence tagged sites (STS), in aggregate representing 120 kb of sequenced DNA, were derived from selected cosmids. Most of these STSs, spaced at an average distance of approximately 35 kb along the euchromatic region of the chromosome, represent DNA tags that can be used as entry points to the fruitfly genome. Furthermore, 42 genes have been placed on the physical map, either through the hybridization of specific probes to the cosmids or through the fact that they were represented among the STSs. These provide a link between the physical and the genetic maps of D. melanogaster. Nine novel genes have been tentatively identified in Drosophila on the basis of matches between STS sequences and sequences from other species. PMID- 7789766 TI - A genetic analysis of intersex, a gene regulating sexual differentiation in Drosophila melanogaster females. AB - Sex-type in Drosophila melanogaster is controlled by a hierarchically acting set of regulatory genes. At the terminus of this hierarchy lie those regulatory genes responsible for implementing sexual differentiation: genes that control the activity of target loci whose products give rise to sexually dimorphic phenotypes. The genetic analysis of the intersex (ix) gene presented here demonstrates that ix is such a terminally positioned regulatory locus. The ix locus has been localized to the cytogenetic interval between 47E3-6 and 47F11-18. A comparison of the morphological and behavioral phenotypes of homozygotes and hemizygotes for three point mutations at ix indicates that the null phenotype of ix is to transform diplo-X animals into intersexes while leaving haplo-X animals unaffected. Analysis of X-ray induced, mitotic recombination clones lacking ix+ function in the abdomen of diplo-X individuals indicates that the ix+ product functions in a cell-autonomous manner and that it is required at least until the termination of cell division in this tissue. Taken together with previous analyses, our results indicate that the ix+ product is required to function with the female-specific product of doublesex to implement appropriate female sexual differentiation in diplo-X animals. PMID- 7789767 TI - P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster. AB - The Drosophila embryonic peripheral nervous system (PNS) is an excellent model system to study the molecular mechanisms governing neural development. To identify genes controlling PNS development, we screened 2000 lethal P-element insertion strains. The PNS of mutant embryos was examined using the neural specific marker MAb 22C10, and 92 mutant strains were retained for further analysis. Genetic and cytological analysis of these strains shows that 42 mutations affect previously isolated genes that are known to be required for PNS development: longitudinals lacking (19), mastermind (15), numb (4), big brain (2), and spitz (2). The remaining 50 mutations were classified into 29 complementation groups and the P-element insertions were cytologically mapped. The mutants were classified in five major classes on the basis of their phenotype: gain of neurons, loss of neurons, organizational defects, pathfinding defects and morphological defects. Herein we report the preliminary phenotypic characterization of each of these complementation groups as well as the embryonic lacZ expression pattern of each P-element strain. Our analysis indicates that in most of the P-element insertion strains, the lacZ reporter gene is not expressed in the developing PNS. PMID- 7789768 TI - Cytogenetic and molecular localization of tipE: a gene affecting sodium channels in Drosophila melanogaster. AB - Voltage-sensitive sodium channels play a key role in nerve cells where they are responsible for the increase in sodium permeability during the rising phase of action potentials. In Drosophila melanogaster a subset of temperature-sensitive paralytic mutations affect sodium channel function. One such mutation is temperature-induced paralysis locus E (tipE), which has been shown by electrophysiology and ligand binding studies to reduce sodium channel numbers. Three new gamma-ray-induced tipE alleles associated with either visible deletions in 64AB or a translocation breakpoint within 64B2 provide landmarks for positional cloning of tipE. Beginning with the flanking cloned gene Ras2, a 140 kb walk across the translocation breakpoint was completed. Germline transformation using a 42-kb cosmid clone and successively smaller subclones localized the tipE gene within a 7.4-kb genomic DNA segment. Although this chromosome region is rich in transcripts, only three overlapping mRNAs (5.4, 4.4, and 1.7 kb) lie completely within the smallest rescuing construct. The small sizes of the rescuing construct and transcripts suggest that tipE does not encode a standard sodium channel alpha-subunit with four homologous repeats. Sequencing these transcripts will elucidate the role of the tipE gene product in sodium channel functional regulation. PMID- 7789769 TI - Structure and regulation of a complex locus: the cut gene of Drosophila. AB - The cut locus encodes a homeobox protein that is localized in the nuclei of a variety of tissues and is required for proper morphogenesis of those tissues. Cut protein is required in embryonic and adult external sensory organs, where its absence results in conversion of the organs to chordotonal organs. Expression of cut also occurs in the Malpighian tubules, spiracles, central nervous system, and a number of other tissues. Gypsy transposon insertions upstream of the cut promoter block expression in subsets of these tissues. The effect of the gypsy insertions is polar, with those farthest from the promoter affecting the fewest tissues. The hypothesis that gypsy insertions block a series of tissue-specific enhancer elements that are distributed over a region of 80 kb upstream of the promoter predicts the location of the enhancers for cut expression in each of the tissues in which it is active in embryos. DNA fragments from this region drive expression of a reporter gene in each of the embryonic tissues in which endogenous cut gene is expressed. Each tissue has its own enhancer, and none of the enhancers require the activity of the endogenous cut gene to function. PMID- 7789770 TI - A genetic analysis of the 63E-64A genomic region of Drosophila melanogaster: identification of mutations in a replication factor C subunit. AB - We have performed an F2 genetic screen to identify lethal mutations within the 63E-64A genomic region. We have isolated 122 mutations in 20 different complementation groups. Of these groups, 16 are represented by multiple alleles. We have also established that the Rop and Ras2 genes are located within the 63E 64A genomic domain at 64A10,11. We have sequenced 10.2 kb of DNA surrounding this gene pair and find that in addition to Rop and Ras2 there is another gene located within this DNA sequence. The gene product, which we have named Rfc40, shows 68% identity to the 40-kDa subunit of replication factor C. We find that the members of one complementation group (13 alleles) derived from our screen correspond to mutations in the Rop gene, whereas the members of another (five alleles) correspond to mutations in the Rfc40 gene. In addition we have isolated 11 new mutant alleles of the disembodied gene. PMID- 7789771 TI - Restriction fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the mosquito Aedes aegypti. AB - Susceptibility of the mosquito Aedes aegypti to the malarial parasite Plasmodium gallinaceum was investigated as a quantitative trait using restriction fragment length polymorphisms (RFLP). Two F2 populations of mosquitoes were independently prepared from pairwise matings between a highly susceptible and a refractory strain of A. aegypti. RFLP were tested for association with oocyst development on the mosquito midgut. Two putative quantitative trait loci (QTL) were identified that significantly affect susceptibility. One QTL, pgs[2,LF98], is located on chromosome 2 and accounted for 65 and 49% of the observed phenotypic variance in the two populations, respectively. A second QTL, pgs[3,MalI], is located on chromosome 3 and accounted for 14 and 10% of the observed phenotypic variance in the two populations, respectively. Both QTL exhibit a partial dominance effect on susceptibility, wherein the dominance effect is derived from the refractory parent. No indication of epistasis between these QTL was detected. Evidence suggests that either a tightly linked cluster of independent genes or a single locus affecting susceptibility to various mosquito-borne parasites and pathogens has evolved near the LF98 locus; in addition to P. gallinaceum susceptibility, this general genome region has previously been implicated in susceptibility to the filarial nematode Brugia malayi and the yellow fever virus. PMID- 7789772 TI - Alternative models for allozyme-associated heterosis in the marine bivalve Spisula ovalis. AB - Correlations between allozyme heterozygosity and fitness-related traits, especially growth, have been documented in natural populations of marine bivalves. However, no consistent pattern has been exhibited, because heterotic effects on size vary with age and individual growth parameters are generally unknown. No consensus has emerged on the genetic basis of allozyme-associated heterosis. The species studied here, Spisula ovalis, displays annual shell growth lines, which allows us to compute individual age and growth dynamics over the whole life span. Our morphological study was coupled to a protein electrophoresis study at seven polymorphic loci. While the maximum size gained is not related to heterozygosity, the age at half maximum size, t1/2, is significantly negatively correlated with heterozygosity, indicating an heterotic effect on initial growth. The correlation between heterozygosity and size is expected to vanish when age increases, due to the form of the growth function. This decreasing correlation is consistent with previous studies. We compare the relative performances of five linear models to analyze the genetic basis of heterosis. Surprisingly, the largest part of variance in t1/2 is due to additive effects, the overdominant components being much weaker. Heterosis is therefore due to general genomic effects rather than to local overdominance restricted to allozymes or small neighboring chromosomal segments. A significant dependence of individual heterotic contributions of the enzyme loci upon expected heterozygosities, rather than metabolic function, further supports the hypothesis of enzymes acting as markers. General genomic effects can hold only if allozyme heterozygosity is positively correlated with heterozygosity at fitness-related genes scattered throughout the genome. This hypothesis is supported here by heterozygosity correlations between enzymatic loci. PMID- 7789773 TI - Half-tetrad analysis in zebrafish: mapping the ros mutation and the centromere of linkage group I. AB - Analysis of meiotic tetrads is routinely used to determine genetic linkage in various fungi. Here we apply tetrad analysis to the study of genetic linkage in a vertebrate. The half-tetrad genotypes of gynogenetic diploid zebrafish produced by early-pressure (EP) treatment were used to investigate the linkage relationships of two recessive pigment pattern mutations, leopard (leo) and rose (ros). The results showed that ros is tightly linked to its centromere and leo maps 31 cM from its centromere. Analysis of half-tetrads segregating for ros and leo in repulsion revealed no homozygous ros individuals among 32 homozygous leo half-tetrads--i.e., a parental ditype (PD) to nonparental ditype (NPD) ratio of 32:0. This result shows that ros is linked to leo, a mutation previously mapped to Linkage Group I. Investigation of PCR-based DNA polymorphisms on Linkage Group I confirmed the location of ros near the centromere of this linkage group. We propose an efficient, generally useful method to assign new mutations to a linkage group in zebrafish by determining which of 25 polymerase chain reaction (PCR)-based centromere markers shows a significant excess of PD to NPD in half tetrad fish. PMID- 7789774 TI - Interval mapping of high growth (hg), a major locus that increases weight gain in mice. AB - The high growth locus (hg) causes a major increase in weight gain and body size in mice. As a first step to map-based cloning of hg, we developed a genetic map of the hg-containing region using interval mapping of 403 F2 from a C57BL/6J-hghg x CAST/EiJ cross. The maximum likelihood position of hg was at the chromosome 10 marker D10Mit41 (LOD = 24.8) in the F2 females and 1.5 cM distal to D10Mit41 (LOD = 9.56) in the F2 males with corresponding LOD 2 support intervals of 3.7 and 5.4 cM, respectively. The peak LOD scores were significantly higher than the estimated empirical threshold LOD values. The localization of hg by interval mapping was supported by a test cross of F2 mice recombinant between the LOD 2 support interval and the flanking marker. The interval mapping and test-cross results indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study. The hg inheritance was recessive in females, although we could not reject recessive or additive inheritance in males. Possible causes for sex differences in peak LOD scores and for the distortion of transmission ratios observed in F2 males are discussed. The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals. PMID- 7789775 TI - Genetics of male sterility in gynodioecious Plantago coronopus. I. Cytoplasmic variation. AB - Inheritance of male sterility was studied in the gynodioecious species Plantago coronopus using five plants and their descendants from an area of approximately 50 m2 in each of six locations. The crosses were planned to test for cytoplasmic inheritance of male sterility. In four locations significant differences between reciprocal crosses were observed. The progenies of these reciprocal crosses were used in a crossing scheme designed to test whether these reciprocal differences were caused by different cytoplasmic types between the plants. In all four locations, the existence of at least two cytoplasmic types could be shown. Moreover, the results of the crosses between locations showed that the same two cytoplasmic types were present in all four locations. We therefore argue that there is only limited cytoplasmic variation in P. coronopus. In each cytoplasmic type a series of intermediate sex forms occurred. A marked difference in restoration level existed between the two cytoplasmic types. Plants with cytoplasmic type 2 hardly segregated male steriles, in contrast to plants with cytoplasmic type 1. PMID- 7789776 TI - Genetics of male sterility in gynodioecious Plantago coronopus. II. Nuclear genetic variation. AB - Inheritance of male sterility was studied in the gynodioecious species Plantago coronopus using five plants and their descendants from an area of approximately 50 m2 from each of four locations. In each location, crosses between these five plants yielded the entire array of possible sex phenotypes. Both nuclear and cytoplasmic genes were involved. Emphasis is placed on the nuclear (restorer) genetics of two cytoplasmic types. For both types, multiple interacting nuclear genes were demonstrated. These genes carried either dominant or recessive restorer alleles. The exact number of genes involved could not be determined, because different genetic models could be proposed for each location and no common genetic solution could be given. At least five genes, three with dominant and two with recessive restorer allele action, were involved with both cytoplasmic types. Segregation patterns of partially male sterile plants suggested that they are due to incomplete dominance at restorer loci. Restorer genes interact in different ways. In most instances models with independent restorer gene action were sufficient to explain the crossing results. However, for one case we propose a model with epistatic restorer gene action. There was a consistent difference in the segregation of male sterility between plants from the two cytoplasmic types. Hermaphrodites of cytoplasmic type 2 hardly segregated male steriles, in contrast to plants with cytoplasmic type 1. PMID- 7789777 TI - Genetic characterization of the Mutator system in maize: behavior and regulation of Mu transposons in a minimal line. AB - Most Mutator lines of maize harbor several different classes of Mu transposons, each of which may be present in high copy number. The regulatory element is also often found in high copy number, and it is this element's behavior that is presumed to cause the non-Mendelian inheritance of Mutator activity. Using a very simple Mutator line, we demonstrate tha MuDR-1, a regulator of the Mutator system, can functionally replace standard non-Mendelian Mutator activity and that MuDR-1 is associated with the loss of methylation of the termini of another Mu transposon. Further, we show that Mu transposons can transpose duplicatively, that reinsertion tends to be into unlinked sites, and that MuDR-1 frequently suffers deletions. Changes in chromosomal position and the mode of sexual transmission are shown to be associated with changes in the frequency of MuDR-1 duplication and with the activity of MuDR-1 as monitored by the excision frequency of a reporter transposon of the Mu family, Mu1. Our data are derived from a Minimal Mutator Line in which there are relatively few Mu transposons, including one MuDR-1 regulator and as few as one Mu1 reporter. The seemingly enigmatic results that have been obtained using more complicated Mu genotypes are reinterpreted using simple Mendelian principles. We have borrowed a gap-repair model from Drosophila biologists to explain both duplications and deletions of MuDR-1. PMID- 7789778 TI - Quantitative genetics of 4x-2x hybrid populations with first-division restitution and second-division restitution 2n gametes produced by diploid parents. AB - A model is proposed to describe the genetic value of 4x-2x hybrids resulting from crosses between tetraploid genitors and diploid genitors that produce 2n gametes. The model takes into account the genetic consequences of the First Division Restitution (FDR) and Second Division Restitution (SDR) meiosis, particularly on the homozygosity level that 2n gametes contribute to 4x-2x hybrids. As genes can be identical by descent, numerous parameters are needed in the classical approach to describe the inbreeding effects on the mean and variance of 4x-2x hybrids. Using the concept of test value, the model allows a large decrease in the number of required parameters. The model gives the components of genetic variance and usual covariances between relatives using these synthetic parameters. The model is then used to study the efficiency of a recurrent breeding scheme to improve diploid genitors for their combining ability with tetraploid genitors. It appears that, in presence of dominance, ignoring the meiosis pattern will lead to an overestimation of additive variance and then of genetic advance. Some genetic considerations on the differences between FDR and SDR mechanisms lead us to suggest an experimental comparison of their respective advantages and disadvantages for the type of considered recurrent selection. An experimental crossing design is proposed to obtain estimates of the genetic parameters needed for this comparison. PMID- 7789779 TI - The population genetics of speciation: the evolution of hybrid incompatibilities. AB - Speciation often results from the accumulation of "complementary genes," i.e., from genes that, while having no deleterious effect within species, cause inviability or sterility when brought together with genes from another species. Here I model speciation as the accumulation of genic incompatibilities between diverging populations. Several results are obtained. First, and most important, the number of genic incompatibilities between taxa increases much faster than linearly with time. In particular, the probability of speciation increases at least as fast as the square of the time since separation between two taxa. Second, as Muller realized, all hybrid incompatibilities must initially be asymmetric. Third, at loci that have diverged between taxa, evolutionarily derived alleles cause hybrid problems far more often than ancestral alleles. Last, it is "easier" to evolve complex hybrid incompatibilities requiring the simultaneous action of three or more loci than to evolve simple incompatibilities between pairs of genes. These results have several important implications for genetic analyses of speciation. PMID- 7789780 TI - Among-environment heteroscedasticity and genetic autocorrelation: implications for the study of phenotypic plasticity. AB - The impact of among-environment heteroscedasticity and genetic autocorrelation on the analysis of phenotypic plasticity is examined. Among-environment heteroscedasticity occurs when genotypic variances differ among environments. Genetic autocorrelation arises whenever the responses of a genotype to different environments are more or less similar than expected for observations randomly associated. In a multivariate analysis-of-variance model, three transformations of genotypic profiles (reaction norms), which apply to the residuals of the model while preserving the mean responses within environments, are derived. The transformations remove either among-environment heteroscedasticity, genetic autocorrelation or both. When both nuisances are not removed, statistical tests are corrected in a modified univariate approach using the sample covariance matrix of the genotypic profiles. Methods are illustrated on a Chlamydomonas reinhardtii data set. When heteroscedasticity was removed, the variance component associated with the genotype-by-environment interaction increased proportionally to the genotype variance component. As a result, the genetic correlation rg was altered. Genetic autocorrelation was responsible for statistical significance of the genotype-by-environment interaction and genotype main effects on raw data. When autocorrelation was removed, the ranking of genotypes according to their stability index dramatically changed. Evolutionary implications of our methods and results are discussed. PMID- 7789781 TI - Satisfaction with and effectiveness of medical care in relation to anxiety and depression. Patient and physician ratings compared. AB - This study examined 1) patient ratings of satisfaction with and effectiveness of medical care, and 2) physician ratings of treatment effectiveness, taking into account personal characteristics, health and mental health of 75 clinic attenders who scored below a cutoff on a screening questionnaire for hypochondriasis. Patients above the cutoff on this instrument, and a random sample of all those below the cutoff, then returned at a later date to undergo a research battery consisting of self-report questionnaires, and structured and semistructured interviews, including the Diagnostic Interview Schedule (DIS). About three fourths of the patients were very satisfied with their medical care, and over half considered the medical care they received effective. Patients and physicians did not concur on the effectiveness of care (r = 0.029, p = 0.81; Kappa = 0.025). Depression was negatively correlated with satisfaction with medical care, r = 0.42, p = 0.0001; anxiety negatively correlated with perceived effectiveness of care, r = -0.41, p = 0.003. Physician rating of effectiveness of care correlated with physician rating of depression, age, and gender (more effective for older and male), (R2 = 0.27, p = 0.0388). We conclude that the lack of agreement between patients and physicians on effectiveness of care suggests the need for better communication. The finding that a depressive diagnosis is associated with dissatisfaction suggests more generally that psychiatric disorder may be an important determinant of patient satisfaction with medical care. PMID- 7789782 TI - Doctor-shopping patients and users of alternative medicine among Japanese primary care patients. AB - To describe the clinical characteristics of patients with doctor-shopping behavior (doctor-shopping patients) and users of alternative medicine among Japanese primary care patients, 1088 patients from the general medicine outpatient clinic of a medical school hospital answered an original questionnaire and 30-item General Health Questionnaire (GHQ). A random sample of patients was questioned in accordance with the Diagnostic Interview Schedule modified for use in Japan (DIS-JM). Twenty-three percent of these patients met our criteria for doctor-shopping patients, and 7.9% had used alternative medicine. Multivariate analysis showed no significant difference between the two groups of patients with regard to sex, age, residence, occupation, education, or marital status. The most striking characteristics of doctor-shopping patients were chronicity of illness (p < 0.005), inability to understand doctors' explanations (p < 0.005), disbelief of the doctor's diagnosis and treatment (p < 0.005), and high GHQ scores (p < 0.05). The major factor for alternative medicine users was high expectations of medical school hospitals (p < 0.01). DIS-JM interviews showed that doctor shopping patients had a high lifetime prevalence of mental disorders. The lifetime prevalence of DSM-III somatization disorders was significantly higher in the two study groups. These results suggest that the risk factors for doctor shopping are strongly associated with chronic conditions and the doctor-patient relationship. Also, users of alternative medicine had high expectations of medical school hospitals as the symbol of modern medicine. Therefore, we emphasize the importance of accurate explanations and maintenance of good doctor patient relationships by physicians providing care. We also suggest that when obtaining the patient's medical history, doctors ask how many prior visits the patient has made to medical facilities with the same complaint, and how many times the patient has used alternative medicine. PMID- 7789783 TI - Psychological responses to malignant melanoma. An investigation of traumatic stress reactions to life-threatening illness. AB - A cross-sectional study of 95 individuals with malignant melanoma was conducted to investigate posttraumatic stress responses to a diagnosis of melanoma and to validate the use of the Impact of Event Scale (IES) as a measure of the response to the trauma of life-threatening disease. The diagnosis and progression of malignant disease are likely to present a range of acute and chronic trauma to the individual and the individual's family. The findings suggest that the IES is a reliable and valid measure of this distress, with scores varying according to disease progression and prognostic status of nonmetastatic disease patients. This indicates the importance of clinical attention to the specific symptoms that may best reflect the traumatic impact of life-threatening illness and its progression, and the applicability of posttraumatic stress syndromes in understanding the psychological distress of this clinical population. PMID- 7789784 TI - Psychiatric aspects of progressive supranuclear palsy. AB - Progressive supranuclear palsy (PSP) is characterized by supranuclear ophthalmoplegia mainly affecting vertical gaze, nuchal dystonia in extension, pseudobulbar palsy, and mental changes. The literature on PSP has been neurologically oriented whereas the psychiatric aspects have been relatively neglected. A review of the literature shows that psychiatric disturbance in PSP is common but with no characteristic pattern. Cognitive impairment, nonspecific affective and behavioral disturbances are commonly found, whereas frank psychosis or bipolar disorder are rare. Misdiagnoses with psychiatric disorders are common and a heightened awareness of the condition is necessary for early diagnosis. PMID- 7789785 TI - Depression and anxiety in an 85-year-old woman with a toxic nodular goiter. AB - Depression is commonly encountered in medical settings and often may be a symptom of an underlying medical illness. This case report illustrates the disabling symptoms of anxiety and depression that can accompany a toxic nodular goiter, and underscores the importance of both accurate psychiatric diagnosis and appropriate medical evaluation in the assessment of psychiatric disorders in the elderly. PMID- 7789786 TI - Sexual and physical abuse history and medical practice. PMID- 7789787 TI - Further analyses of the Delirium Rating Scale. AB - The Delirium Rating Scale is a clinician-rated, 10-item symptom rating scale for assessment of delirium severity. In order to better understand the relationship between items of the scale and whether they reflect one or more underlying groupings or dimensions, further analyses of the originally published scale data were performed. Factor analysis revealed a strong single underlying dimension that could be further divided into two components: one comprising delusions, psychomotor behavior, cognition, sleep-wake cycle disturbance, and mood lability; the other comprising temporal onset of symptoms, perceptual disturbances, hallucinations, and fluctuation of symptoms. Implications for improved phenomenological understanding of delirium are discussed. PMID- 7789788 TI - The ethical limits of confidentiality in the therapeutic relationship. AB - The author explores the moral underpinnings of psychiatric confidentiality in an attempt to define its ethical limits. Knowledge of this standard assumes growing importance as third party incursions into the patient-therapist dyad become increasingly common in day-to-day practice. The APA's AIDS policy on confidentiality and disclosure is offered as an illustrative example of the profession's ability to successfully translate moral deliberation into clinical policy. PMID- 7789789 TI - Medical and psychiatric symptoms in female gastroenterology clinic patients with histories of sexual victimization. AB - Several recent retrospective reports have associated prior sexual victimization and long-term medical sequelae such as increased medical clinic utilization and reports of physical symptoms. However, methodological constraints have limited the generalizability of these findings. Our study was designed using structured interviews with a sequential sample of 89 female gastroenterology clinic patients, who were classified by severity of sexual trauma and studied for differences in lifetime psychiatric diagnoses, physical abuse, and medically unexplained symptom patterns. Compared with the 46 women who had experienced less severe or no prior sexual trauma, the 43 patients with severe victimization had significantly higher life-time and current rates of several selected psychiatric disorders as well as significantly higher mean numbers of lifetime psychiatric disorders, medically unexplained physical and anxiety symptoms, greater harm avoidance and dissociation scores, and increased functional disability. A logistic regression showed that the main predictors of a history of severe sexual abuse were the number of medically unexplained symptoms, adult physical abuse, and lifetime dysthymic disorder. We concluded that women with prior severe sexual trauma episodes may express medically unexplained physical symptoms as part of the long-term adaptation to their victimization. PMID- 7789791 TI - The dihydrofolate reductase-encoding gene dyrA of the hyperthermophilic bacterium Thermotoga maritima. AB - The structural gene (dyrA) encoding dihydrofolate reductase (DHFR) of Thermotoga maritima has been cloned, sequenced and expressed in Escherichia coli. The dyrA gene, located immediately upstream from the gene encoding aspartate carbamoyltransferase (pyrB), encodes a highly thermostable enzyme with a distinct thermophilic activity profile. Important structural features are conserved among all bacterial DHFR, yet the DHFR of T. maritima appears unique in a number of insertions and deletions, some of which are reminiscent of eukaryotic DHFR. PMID- 7789790 TI - Recognizing and managing depression in primary care. AB - Depression is a common disorder in the primary care setting; it is associated with considerable distress and dysfunction. The management of depressed primary care patients can be complicated by the fact that these patients may lack insight into the cause of their symptoms and report only the somatic manifestations of their disorder to their physicians. Primary care patients may also be reluctant to accept a diagnosis of depression or referral to a mental health specialist. Primary care physicians may feel they lack the time or the training to adequately address their patients' depressive disorders. This paper presents a model for identifying, evaluating, and treating depression which has been specifically developed to help primary care physicians overcome these barriers. PMID- 7789792 TI - Cloning and characterization of the lipase operon from Mycoplasma mycoides subspecies mycoides LC. AB - Lipases, serine esterase enzymes, play an essential role in the mycoplasmal nutritional requirement for long-chain fatty acids. Although the lipase(s) activity in different mycoplasma species has been investigated, the molecular biology of the corresponding genes has not been studied. Using a single-primer PCR technique combined to more classical cloning systems, an operon containing three open reading frames (ORF), each of which could encode a lipase protein of 264, 264 or 269 amino acids (aa), was identified from Mycoplasma mycoides subsp. mycoides LC. Analysis of aa sequences of the encoded polypeptides showed that they display high aa similarity between each other (65-79%) and 28-31% identity to other prokaryotic lipases. Moreover, a lipase-esterase activity could be detected when the mycoplasmal lipase-encoding genes were expressed in a strong opal-suppressor-bearing Escherichia coli strain. PMID- 7789793 TI - Gene disruption with PCR products in Saccharomyces cerevisiae. AB - We describe here the generation of gene disruption constructs using PCR amplification of selectable markers with primers that provide homology to the target gene of interest. We find that regions of homology as short as 38 to 50 bp suffice to mediate homologous recombination in yeast. We describe applications of this technology to three specific yeast genes that would have been difficult to disrupt with current methods. By dispensing with the need to either clone the gene of interest or engineer a standard disruption construct, this method should facilitate analysis of sequenced genes of unknown function, which will soon include the entire yeast genome. PMID- 7789794 TI - A mini-promoter lacZ gene fusion for the analysis of fungal transcription control sequences. AB - A system for the in vivo analysis of fungal transcription control sequences, based on a mini-promoter, was designed. The mini-promoter, providing all sequences necessary and sufficient for transcription initiation, was derived from the Aspergillus nidulans gpdA promoter region. Transcription initiation was not affected by the introduction of transcription control sequences directly upstream from the mini-promoter. Furthermore, the expression of the mini-promoter was not affected by wide-domain carbon or nitrogen control circuits. Using the mini promoter vector, a previously identified upstream activating sequence from the A. nidulans gpdA gene was further characterized. PMID- 7789795 TI - Cloning, characterization and functional expression of an endoglucanase-encoding gene from the phytopathogenic fungus Macrophomina phaseolina. AB - An endoglucanase-encoding clone (egl2) was isolated from the phytopathogenic soilborne deuteromycete fungus Macrophomina phaseolina (Mp). Clones were obtained from a cDNA library by functional expression in Escherichia coli. The egl2 clone hybridized to a 1.3-kb mRNA. Expression is induced by carboxymethylcellulose (CMC) and repressed by glucose. The deduced amino acid (aa) sequence revealed strong similarity to the egl3 from Trichoderma reesei (Tr) (72% for identical residues and 81% with conservative substitution over a span of 324 aa). The Mp egl2 lacks the cellulose-binding domain and linker region found in the Tr egl3. Different codon usage between the two fungi resulted in a much shorter span of nucleotide homology. The Egl2 protein cleaves cellodextrins with continguous beta, 1-4 linkages of four and larger, and shows activity against CMC and birchwood xylan. PMID- 7789796 TI - Sequences at four termini of the giardiavirus double-stranded RNA. AB - The linear double-stranded RNA (dsRNA) genome of giardiavirus (GLV) was estimated to be 6100 nucleotides (nt) [Wang et al., Proc. Natl. Acad. Sci. USA 90 (1993) 8585-8599]. As the 5'- and 3'-untranslated regions (UTR) of viral genomes are known to contain critical information for viral replication, we reexamine the sequences at all four termini of GLV dsRNA by (i) direct RNA sequencing with RT, (ii) tailing GLV dsRNA with UTP or CTP in addition to ATP in 3' rapid amplification of cDNA ends (RACE) and (iii) adding poly(dG) to the products of primer extension in 5'-RACE. The results confirmed the reported sequence for the 5'-terminus of the GLV sense strand RNA, but uncovered an additional 177 nt at the 3'-terminus. The new study also showed conclusively that there are no protruding overhangs at either terminus of GLV dsRNA. PMID- 7789798 TI - Isolation and characterization of a new restriction endonuclease, Sru30DI, from Selenomonas ruminantium. AB - The restriction endonuclease (ENase) Sru30DI, an isoschizomer of StuI, which recognizes the sequence 5'-AGG/CCT-3', was purified from a natural isolate of Selenomonas ruminatinum. The ENase was isolated from cell extracts using single step purification by phosphocellulose column chromatography. Activity of Sru30DI is inhibited by overlapping Dcm methylation. The ENase is extremely stable at 37 degrees C and is active over a wide range of pH, temperature and salt concentrations. PMID- 7789797 TI - Cloning of a new cation ATPase from Plasmodium falciparum: conservation of critical amino acids involved in calcium binding in mammalian organellar Ca(2+) ATPases. AB - In order to study molecules that may be involved in pH gradient formation in Plasmodium, we have identified a novel cation-translocating ATPase (P-type ATPase) gene from P. falciparum (Pf). We report the full-length nucleotide and deduced amino acid (aa) sequences of this gene that we called PfATPase4. The PfATPase4 protein shares features with the different members of eukaryotic P-type ATPases, such as a similar transmembrane (TM) organization and aa identity in functionally important regions. Interestingly, the PfATPase4 protein possesses conserved aa involved in calcium binding in mammalian organellar Ca(2+)-ATPases. PMID- 7789799 TI - An arabinose-inducible expression vector, pAR3, compatible with ColE1-derived plasmids. AB - Arabinose-inducible genetic elements from the Salmonella typhimurium arabinose operon were inserted into pACYC184. The resultant plasmid, pAR3, is compatible with ColE1-derived plasmids and allows efficient expression of recombinant (re) genes upon induction with arabinose. These features make it convenient for use in combination with standard gene expression vectors for the independently controlled production of two or more re-polypeptides in Escherichia coli. PMID- 7789800 TI - Nucleotide sequence of a small plasmid isolated from Acetobacter pasteurianus. AB - A 1440-bp plasmid named pAP12875 was isolated from Acetobacter pasteurianus and its nucleotide sequence determined. An open reading frame was found capable of coding for a protein that has similarity with the replication protein of pVT736-1 from Actinobacillus actinomycetemcomitans and the 32-kDa protein of phage Pf3 from Pseudomonas aeruginosa. PMID- 7789802 TI - Cloning and sequencing of the neutral protease-encoding gene from a thermophilic strain of Bacillus sp. AB - The neutral protease-encoding gene (npr) from the thermophilic strain Bacillus sp. BT1 was cloned and sequenced. A possible means of regulation of npr expression is suggested. PMID- 7789801 TI - Diversity of the transferrin-binding protein Tbp2 of Neisseria meningitidis. AB - In order to investigate the genetic basis for the observed polymorphism amongst meningococcal transferrin-binding proteins, Tbp2, the corresponding genes of different Neisseria meningitidis strains were cloned and sequenced. Comparison of the deduced amino acid (aa) sequences indicated that the Tbp2 were 76.6 to 81.2% homologous. Several stretches of aa have been found repeated both in the N- and C terminal halves of the molecule. PMID- 7789803 TI - Sequence of a P-methyltransferase-encoding gene isolated from a bialaphos producing Streptomyces hygroscopicus. AB - The nucleotide sequence of the Streptomyces hygroscopicus gene encoding P methyltransferase, catalyzing the formation of a carbon-phosphorus bond, involved in bialaphos biosynthesis, has been determined. The amino-acid sequence deduced from the nt sequence, shows homology with those of magnesium-protoporphyrin IX monomethyl ester oxidative cyclase (Mg-ProtoMe cyclase) of Rhodobacter capsulatus and the enzyme catalyzing the methylation of the aldehyde carbon of phosphonoacetaldehyde in fosfomycin biosynthesis. PMID- 7789804 TI - An improved system for gene replacement and xylE fusion analysis in Pseudomonas aeruginosa. AB - A novel pUC19-based gene replacement vector has been developed. This vector incorporates (i) the counterselectable sacB marker, (ii) a lacZ alpha allele for blue-white screening, (iii) an oriT for conjugation-mediated plasmid transfer and (iv) unique cloning sites for SmaI and the rare-cutting meganuclease I-SceI. These rare restriction sites are also present on the helper plasmid pUC19Sce. The replacement vector is engineered to contain few restriction sites to gain greater access to restriction sites within cloned DNA fragments, thus facilitating their genetic manipulation. The usefulness of the system was demonstrated by chromosomal integration of a newly constructed xylE::GmR fusion cassette into the glpD gene of Pseudomonas aeruginosa. PMID- 7789805 TI - Cloning and sequencing of the Bordetella pertussis cpn10/cpn60 (groESL) homolog. AB - The nucleotide sequence downstream from the Bordetella resistance to killing (brk) locus in Bordetella pertussis was determined. Analysis of the sequence revealed an operon consisting of two highly predicted open reading frames (ORFs). The deduced amino-acid sequence of each ORF has strong homologies to the heat shock proteins/chaperonins Cpn60 and Cpn10. The promoter contains consensus sequences for both sigma 32 and sigma 70 binding, and it possesses the CIRCE regulatory inverted repeat. A potential Rho-independent terminator was identified and appears to be shared with the brkA gene. PMID- 7789806 TI - The nitrate and nitrite reductase-encoding genes of Leptosphaeria maculans are closely linked and transcribed in the same direction. AB - The 5' flanking region and the first 704 bp of the nitrite reductase-encoding gene (niiA) of Leptosphaeria maculans has been sequenced. The niiA start codon is 1438 bp downstream from the stop codon of the nitrate reductase-encoding gene (niaD) and the two genes are transcribed in the same direction. PMID- 7789807 TI - The gene encoding the beta-1,4-endoglucanase (CelA) from Myxococcus xanthus: evidence for independent acquisition by horizontal transfer of binding and catalytic domains from actinomycetes. AB - The celA gene encoding a beta-1,4 endoglucanase (CelA) from Myxococcus xanthus has been cloned in Escherichia coli and sequenced. The C-terminal region of CelA displayed a high level of similarity with the catalytic domain of several Egl belonging to the glycosyl hydrolases family 6 (CenA from Cellulomonas fimi, CelA from Microbispora bispora, E2 from Thermonospora fusca, CasA from Streptomyces KSM9 and CelA1 from Streptomyces halstedii) and less similarity to the cellobiohydrolases of the fungi Trichoderma reesei and Agaricus bisporus. Using PCR amplification we found in another myxobacterium, Stigmatella aurantiaca, a part of a glycosyl hydrolase belonging to the same family. The N-terminal part of CelA displayed significant similarities with the cellulose-binding domain of other cellulases belonging to a rare subset of family II, such as the avicelase I from Streptomyces reticuli, both tandem repeats N1 and N2 of the cellulase CenC from Cellulomonas fimi, and the N-terminal part of the Egl E1 from Thermonospora fusca. Analyses of the multiple alignments and reconstruction of phylogenetic trees strongly suggest that both domains of CelA were acquired by independent horizontal transfers between Gram+ soil bacteria and scavenging myxobacteria followed by domain shuffling. PMID- 7789808 TI - A mutualistic fungal symbiont of perennial ryegrass contains two different pyr4 genes, both expressing orotidine-5'-monophosphate decarboxylase. AB - A fragment of the Claviceps purpurea pyr4 gene, encoding orotidine-5' monophosphate decarboxylase (OMP decarboxylase), was used to screen a genomic library from an isolate of a fungus, Acremonium sp. (designated Lp1), which grows as an endophyte in perennial ryegrass (Lolium perenne). Three positive clones, lambda MC11, lambda MC12 and lambda MC14, were isolated. Two of these clones, lambda MC12 and lambda MC14, were overlapping clones from the same locus, while lambda MC11 was from a different locus. Fragments of these clones which hybridised with C. purpurea pyr4 were sequenced and found to have similarity with pyr4 from other Pyrenomycete fungi. The pyr4 gene from lambda MC12 and lambda MC14 was designated pyr4-1 and that from lambda MC11 was designated pyr4-2. The predicted ORFs of the two genes were highly conserved, with 97.5% identity at the nucleotide level, the 5' non-coding sequences were the least conserved with 88.5% identity and the 3' non-coding sequences had 93.0% identity. RT-PCR analysis of total RNA from Lp1 demonstrated that transcripts from the two genes were present at similar levels, and hybridisation of pyr4-1 to Northern blots of total RNA from Lp1 showed that full-length transcripts were being produced. Genomic fragments containing pyr4 were transformed into a strain of Aspergillus nidulans which has a mutation in pyrG (encoding OMP decarboxylase). Both pyr4-1 and pyr4-2 complemented the pyrG mutation in A. nidulans, indicating that both encode functional OMP decarboxylases. It has been proposed [Schardl et al., Genetics 136 (1994) 1307-1317] that the two pyr4 in Lp1 arose by interspecific hybridisation, most likely between the ryegrass choke pathogen, Epichloe typhina, and another endophyte from perennial ryegrass, Acremonium lolii. Analysis by PCR amplification and direct sequencing of the variable 5' non-coding regions of pyr4, from possible ancestors to Lp1 supports this hypothesis. Comparisons of these sequences to the 5' non-coding sequences from pyr4-1 and pyr4-2 demonstrated that E. typhina and A. lolii were the most likely ancestors of the two pyr4 found in Lp1. PMID- 7789810 TI - The pTugA and pTugAS vectors for high-level expression of cloned genes in Escherichia coli. AB - Plasmids pTugA and pTugAS, designed for expression of cloned genes in Escherichia coli, possess the features of high-level inducible transcription, enhanced RNA translation, portability, high copy number, stability and versatility. In addition, pTugAS can be used to produce fusion proteins comprising a target protein and a cellulose-binding domain. Such fusion proteins can be purified in a single step by affinity chromatography on cellulose. Expression of two model gene fusions using the pTug plasmids resulted in yields of 500 mg of intracellular and 250 mg of extracellular recombinant protein per liter. PMID- 7789809 TI - Analysis of a family of ypt genes and their products from Chlamydomonas reinhardtii. AB - Small G-proteins encoded by the ras-like ypt genes are ubiquitous in eukaryotic cells. They have been shown to play an essential role in membrane vesicle transport. We have isolated four ypt genes, yptC1, yptC4, yptC5 and yptC6, from Chlamydomonas reinhardtii (Cr) genomic and cDNA libraries. Three of them, yptC1, yptC4 and yptC5, are close homologues of ypt genes previously found in the multicellular alga Volvox carteri (Vc), the fourth, yptC6, is new. Each yptC gene is present as a single copy in the genome. Comparisons of genomic and cDNA sequences revealed that the coding regions are interrupted by five (yptC5), six (yptC6), seven (yptC4) and eight (yptC1) introns, respectively. Cr ypt genes and the closely related Vc ypt genes have identical exon-intron structures, but the corresponding intron sequences are completely different. Polyadenylation is signalled by UAUAA, UGUAG and UGUAA. The deduced amino acid (aa) sequence of YptC6 exhibited 79% identity with HRab2; YptC1, YptC4 and YptC5 exhibited over 90% identity with their Vc homologues. Primary structures of the 9-aa 'effector domain' and the contiguous 'helix3-loop7' motif (approx. 30 aa) are 'diagnostic' features for functional assignment. Recombinant YptC proteins, overproduced in Escherichia coli and purified to near homogeneity, displayed strong and specific binding of GTP, but not of GMP or ATP. The four Cr Ypt proteins showed immunochemical cross reactions to their Vc counterparts. Moreover, Western blots demonstrated at least six types of Ypt in both Cr and Vc, suggesting that these Ypt are used for household functions responsible for vesicle transport rather than for cellular differentiation. PMID- 7789811 TI - A point mutation in a murine immunoglobulin V-region strongly influences the antibody yield in Escherichia coli. AB - Recombinant DNA technology has made it possible to produce specific Fab and scFv antibody (Ab) fragments in prokaryotic host cells. Using vectors designed for periplasmic expression of encoded Ab fragments, we have been studying how the sequence and genetic localization of the light chain (L-chain) variable region gene of a mouse Ab (CB-Nm.1) determined the level of Ab production. The variable region was shown to belong to the V kappa V family and contained a previously unreported Ile72. Nine different Ab constructions were tested in monocistronic (scFv) or dicistronic (Fab) operons for their ability to affect the synthesis level of the L-chain. When the gene coding for the L-chain was located downstream from the Fd fragment gene, the substitution of codons encoding Ile by a codon encoding Thr was found to be crucial for any expression of the L-chain fragment. This was, however, not accompanied by an increase in L-chain-specific mRNA, neither was there any change in the size of the mRNA. The fact that the unmutated L-chain protein was produced from cells transformed with certain other constructions indicated that the protein as such was not incompatible with the prokaryotic environment. Together, this suggested that the translation process was involved in the restricted production of the L-chain. Thus, surprisingly small substitutions significantly affected the expression level, a fact that will have important implications on the library size expressed in prokaryotic hosts, including phage-displayed Ab libraries. PMID- 7789813 TI - Characterization of an open reading frame involved in site-specific integration of filamentous phage Cf1t from Xanthomonas campestris pv. citri. AB - Cf1t is a single-stranded DNA filamentous phage; a 1.9-kb segment of DNA from Cf1t was found to be responsible for site-specific integration into Xanthomonas campestris pv. citri (XW47), in the absence of any Xanthomonas origin of replication. Deletion analysis and introduction of amber stop codons into this fragment from Cf1t revealed an open reading frame (ORF344) which was involved in the integration function. The predicted amino-acid sequence of ORF344 bears no homology with conserved sequences of the integrase family. PMID- 7789812 TI - Isolation and characterization of ompS1, a novel Salmonella typhi outer membrane protein-encoding gene. AB - We have isolated a novel outer membrane protein (OMP)-encoding gene from Salmonella typhi (St), termed ompS1, using the ompF gene of Escherichia coli (Ec) as a heterologous probe. The structural ompS1 gene codes for an OmpS1 polypeptide that consists of 373 amino acids (aa) in the mature product, with a putative 21 aa leader sequence, containing highly conserved aa residues that have been implicated in pore formation. Mature OmpS1 (41 kDa) is larger than the OmpC, OmpF and PhoE St and Ec porins. In contrast to the major porins, it is undetectable in Coomassie-stained OMP preparations; although, when ompS1 was cloned into a high copy-number plasmid under the control of the inducible tac promoter, it was detectable along with major OMPs. The 5' regulatory region of ompS1 has five putative binding sites for OmpR, a positive transcriptional regulator. The ompS1 gene shows restriction-fragment length polymorphism (RFLP) among Salmonellae. PMID- 7789814 TI - Cloning and study of the genetic organization of the exe gene cluster of Aeromonas salmonicida. AB - The Aeromonas salmonicida (As) exe gene cluster, an additional member of the pul related operon family required for general signal-sequence-dependent secretion of proteins from Gram- bacteria, was cloned in the broad-host-range cosmid pLAFR3. Twelve genes, exeC-N, were identified by partial nucleotide (nt) sequence analyses (exeE-N) or determination of the complete sequence (exeC and exeD). The organisation of the exeC-N genes is similar to that of several other operons of this family. These genes are arranged contiguously and are apparently transcribed in the same direction. On alignment of As and A. hydrophila exe sequences a 73-bp 'silent' deletion was identified close to the end of the As exeF gene. No gene encoding prepilin peptidase (the PulO homolog) was detected in this region. The exeN gene is evidently the last gene of this operon; it is followed by an ORF encoding a putative transcription regulator. PMID- 7789815 TI - Cloning and sequencing of a beta-lactamase-encoding gene from the insect pathogen Bacillus thuringiensis. AB - A beta-lactamase (Bla)-encoding gene (bla) from Bacillus thuringiensis (Bt) was cloned and the nucleotide (nt) sequence was determined. Both the nt sequence and deduced amino acid sequences reveal that the Bt Bla is very similar to that of B. cereus and other group A Bla. The transcription start point was also determined. Comparison of the upstream region of Bt bla with that of other genes suggested the presence of three sequence elements that might be involved in promoter function: the -10 (TCGGTGAT) and -35 (TTAT) sequences, an A+T-rich region (5'TACTAGCTATAATTTTTTAGT) and an inverted repeat sequence (5' GAGATAGAGGC[GCTACTATCTC). PMID- 7789816 TI - Cloning and sequence determination of the aspartase-encoding gene from Brevibacterium flavum MJ233. AB - A 2.5-kb EcoRI fragment containing the aspartase-encoding gene (aspA) of Brevibacterium flavum MJ233 was cloned into plasmid pUC18 using Southern hybridization with the Escherichia coli aspA gene as a probe. The complete nucleotide (nt) sequence of the cloned DNA indicated that the deduced gene product of the Br. flavum aspA is composed of 526 amino acids (aa). Comparison of the aa sequence to the corresponding sequences from E. coli, Bacillus subtilis and Pseudomonas fluorescens revealed 63, 47 and 57% homology, respectively. The aspA product was determined to have a size of approx. 57 kDa by SDS-PAGE. PMID- 7789817 TI - Gene disruption in Escherichia coli: TcR and KmR cassettes with the option of Flp catalyzed excision of the antibiotic-resistance determinant. AB - Two cassettes with tetracycline-resistance (TcR) and kanamycin-resistance (KmR) determinants have been developed for the construction of insertion and deletion mutants of cloned genes in Escherichia coli. In both cassettes, the resistance determinants are flanked by the short direct repeats (FRT sites) required for site-specific recombination mediated by the yeast Flp recombinase. In addition, a plasmid with temperature-sensitive replication for temporal production of the Flp enzyme in E. coli has been constructed. After a gene disruption or deletion mutation is constructed in vitro by insertion of one of the cassettes into a given gene, the mutated gene is transferred to the E. coli chromosome by homologous recombination and selection for the antibiotic resistance provided by the cassette. If desired, the resistance determinant can subsequently be removed from the chromosome in vivo by Flp action, leaving behind a short nucleotide sequence with one FRT site and with no polar effect on downstream genes. This system was applied in the construction of an E. coli endA deletion mutation which can be transduced by P1 to the genetic background of interest using TcR as a marker. The transductant can then be freed of the TcR if required. PMID- 7789818 TI - A promoter-screening plasmid and xylose-inducible, glucose-repressible expression vectors for Staphylococcus carnosus. AB - We describe a series of plasmid vectors for DNA cloning in staphylococci. pPS11 is a promoter probe plasmid containing a promoterless lipase (Lip)-encoding gene (lip). Insertion of a promoter-bearing DNA fragment at the single BamHI site turns on lip expression. Lip activity can be easily determined to estimate the strength of the inserted promoter. pPS11 served also as a basis for the construction of vectors which allow xylose-inducible gene expression in Staphylococcus carnosus (Sc). Using plasmid pCX15, we studied xylose-inducible lip expression in Sc. The lip expression is under transcriptional control of the repressor, XylR. The xylR gene, the XylR target sequence and the xylA promoter/operator sequence with the cis-acting catabolite-responsive element (cre) are derived from the xyl operon of S. xylosus. The single BamHI site in front of the lip ribosome-binding site (RBS) also makes it possible to put other promoterless genes under transcriptional control of XylR. To facilitate the controlled expression of genes which merely start with the start codon and have no RBS, or to insert genes with their own RBS, pCX26 and pCX26 delta lip were constructed. The influence of xylose and glucose on lip expression was studied both in a batch culture and in a fermentor under controlled pH conditions. With pCX15, the presence of xylose led to a 40-fold increase in extracellular Lip activity, while the presence of glucose caused a repression of lip expression. The results suggest that the xylA promoter is subject to two different regulatory mechanisms, one of which involves the repression of the xylA promoter by XylR in the absence of xylose, and the other involves a glucose-mediated catabolite repression which dominates over the xylose induction. PMID- 7789819 TI - Complementation of a Streptomyces lividans Leu- mutant by the Actinoplanes teichomyceticus leuC gene. AB - A leucine auxotroph of Streptomyces lividans (Sl), designated PC196, was unable to convert alpha-isopropylmalate into the beta-isomer. A DNA fragment from Actinoplanes teichomyceticus (At) cloned into the Streptomyces vector pIJ702 complemented PC196. Sequence analysis of the 3.0-kb insert revealed one complete ORF with high similarity to other leuC genes encoding the large subunit of isopropylmalate isomerase (IPMI), and the 5' end of a second ORF corresponding to leuD, which encodes the smaller subunit of IPMI. Further subcloning established that Sl strain PC196 is defective in the large subunit of IPMI. PMID- 7789820 TI - [Current approaches to the prevention of cochlear disorders during periodic physical examination of workers, exposed to noise]. PMID- 7789821 TI - [Predicting skin allergy in workers exposed to chemical allergens]. AB - A system for predicting the risk of contact dermatosis in workers handling chemical allergens (epoxy resins) was developed. The accuracy of forecast is up to 86 per cent due to use of anamnestic, clinical, and immunological data. This system can be useful for prophylaxis of contact dermatitis at enterprises where chemical allergens are used. PMID- 7789823 TI - [Factual nutritional status in workers of a machine-building factory]. AB - Physical development, energy expenditures, morbidity, and supply with the main food-stuffs were studied in machine-building workers. Peculiarities of alimentary status of workers were basis for development of hygienic recommendations on rationalization of their nutrition. PMID- 7789822 TI - [Changes of regional hemodynamics in lead manufacturing workers]. PMID- 7789824 TI - [Evaluation of reserved potentials of respiration, cardio- and hemodynamics in young athletes]. PMID- 7789825 TI - [Pedagogic and hygienic aspects of utilization of computer-assisted automated instructions]. PMID- 7789827 TI - [Methods of development of a data bank on ecologic and hygienic characteristics of chemical environmental pollutants]. PMID- 7789828 TI - [Methods of correlation of population health and hygienic and other factors]. PMID- 7789829 TI - [New hygienic methods of blockage of climate disadaptation and climate-related reactions]. PMID- 7789826 TI - [Radiation status in Moscow and Moscow region effected by radiation fallout during 1989 -- 1993 gg]. PMID- 7789830 TI - [Visual productivity of near-sighted computer users working with various colored display screens]. PMID- 7789831 TI - [Basic goals of psychological hygiene in connection with distraction of the chemical weapon]. PMID- 7789832 TI - [Evaluation of maximal permissible concentration of 2-allyl oxyethanol in the atmospheric air]. AB - The threshold irritable concentration of 2-allyl oxyethanol (2-AOE) in ambient air was determined at the level of 0.68 mg/m3. The threshold of chronic effect of 2-AOE is 0.075 mg/m3. The mean daily permissible concentration of 2-AOE is suggested at the level of 0.01 mg/m3. PMID- 7789833 TI - [Effect of electric field of industrial frequency on the changes of micronucleus test and electric conductivity in laboratory animals]. PMID- 7789834 TI - [Social and hygienic monitoring]. PMID- 7789835 TI - [Memorable dates and anniversaries in the history of hygiene and sanitation in 1995]. PMID- 7789837 TI - [Modernization of equipment and methods of its utilization for evaluation of air microbiology]. PMID- 7789838 TI - [Organization of quality control of an accredited laboratory]. PMID- 7789836 TI - [Evaluation of toxic substances in vodka and drinking alcohols by gas liquid chromatography]. PMID- 7789839 TI - [Effect of sanitary and hygienic conditions of populated placed on the incidence of intestinal diseases]. AB - Data on the relationship between the incidence of intestinal infections, including hepatitis A, and communal conditions of settlements and quality of drinking water are presented. PMID- 7789841 TI - [Commemorative centenary of Felix Marchand's description of gestational trophoblastic tumors]. PMID- 7789840 TI - [Anionic surface active substances used for prevention of salt concentration in irrigated lands of hot regions]. AB - Anionic surfactant PO-ID at the level of 10, 25 and 50 kg/ha did not depress biological activity of soil and stimulated nitrogen metabolism. Water-migration and translocation indexes of this surfactant should be studied. PMID- 7789842 TI - [Management of pregnant women with human immunodeficiency virus (HIV) infection]. PMID- 7789843 TI - [Treatment of puerperal endometritis]. PMID- 7789844 TI - [Placenta praevia. Maternal and perinatal repercussions. Analysis of 170 cases]. AB - One hundred and seventy cases with placenta previa, at Instituto Nacional de Perinatologia, from 1989 to 1993, were reviewed. Incidence in our population was 0.62%; average maternal age was 31 years; the greater amount of cases was among nulliparae; in 72% of them there was the antecedent of uterine scar. Ultrasound diagnosis was done in 81% of the patients, and most frequent placental insertion type was the low one in 49%, and in 31%, total, central placenta. The first hemorrhagic episode occurred at a gestational age of 34 weeks. Most frequent complication was threatening pre-term delivery, and ethinyl adrianol was used as uterine inhibitor. All pregnancies were interrupted, via abdominal. Placental accretion was a frequent complication. Hemorrhage during the second half of gestation is one of the main causes of perinatal morbidity-mortality. Frequency of this complication is from 3% to 5%, of all pregnancies in an open population; and when it appears, is one of the most serious urgencies; so its early diagnosis and opportune treatment will diminish maternal and perinatal morbidity-mortality. Etiology is unknown, but diminished endometrial vascularization, at fundus and body, may be the causal factor. There are other predisposing causes as age, advanced maternal age, multiparity, tumours, scars and smoking. The objective of this study, was to analyze maternal and perinatal repercussions, of placenta previa, based on the experience at Instituto Nacional de Perinatologia. PMID- 7789845 TI - [Perinatal morbidity and mortality in pregnant women with diabetes mellitus]. AB - The purpose of this study was to investigate the perinatal morbidity and mortality in all the diabetic pregnancies seen at the HGO-"LCA" from January 1992 to December 1993. In that period 186 women (mean age 31 yr) were diagnosed as having diabetes during pregnancy: 54% of them had DMG, 40% DM-II and 6% DM-I, with serum glucose concentration of 133 +/- 41 mg/dL. Neonatal morbidity was given by macrosomia (17%), prematurity (14%), hyperbilirubinemia (11%), hypoglycemia (8%), congenital malformation (6%) and hypocalcemia (4%). Perinatal mortality was 5.3%. The principal causes of maternal morbidity were preeclampsia (17%), polyhydramnios (16%), pyelonephritis (4%) and ketoacidosis (0.05%). Cesarean section was performed in 62% of all diabetic patients. There was not any maternal death. This results showed a high perinatal morbidity-mortality in pregnancies complicated by diabetes mellitus which reclaim a better metabolic control during gestation period. PMID- 7789846 TI - [Perinatal mortality]. AB - Eighty six cases of perinatal mortality at Hospital de Ginecoobstetricia, Garza Garcia, N.L. Subsecretaria Estatal, from january, 1992 to December, 1993, were reviewed. Perinatal mortality was 12.0 by one thousand births, less than in other reports. The highest incidence was in young patients, 20 to 29 years old, with 47.7% and with parity of 1 to 3, 80.2%; highest frequency in term pregnancies, 37 to 42 weeks, 39.6%; 35% of the products with weight over 2,500 g; and 65% with lesser weight; fetal death occurred most frequently during pre-partum, 55.8%, and less during intra-partum, 19.8%. Most frequent causes of peri-natal death were placental failure, 27.9% and fetal immaturity, with 24.4%. It is concluded that an adequate pre-natal control and delivery surveillance produce a diminution in fetal mortality. PMID- 7789847 TI - [Brucellosis in pregnancy: course and perinatal results]. AB - Brucellosis is a zoonosis that affect cows, goats and pigs, but in endemic zones human beings are frequently infected. Brucella infection in animals is associated with a high incidence of abortion, in humans a cause-effect relationship has not been proven. We present four cases of pregnant women with Brucella infection, all were treated only with rifampin, the patients had adequate obstetric evolution, the deliveries were at term and there were not birth defects or intrauterine growth retardation. One woman had a relapse during her puerperium. In the medical literature review there were not enough support to attribute to brucellosis as causal factor of abortion in humans. The treatment during pregnancy must include the combination of rifampin with another antibiotic with intracellular action. PMID- 7789849 TI - [Advanced cervix uteri carcinoma in a patient with acquired human immunodeficiency virus infection. Case report and review of the literature]. AB - A case of cervix uterine carcinoma concomitant with HIV infection was described. The patient was treated with radical radiation therapy and the course of the neoplastic disease was not modified for the HIV infection. The tolerance and final result of the treatment, and the importance of the early screening of the HIV infection and the carcinoma of the cervix uterine was discussed. PMID- 7789848 TI - [Triple mechanical heart valve prosthesis and pregnancy]. AB - A very unusual case, of a multiparous, 36 year-old, woman, she had previous mechanical replacement of her mitral, aortic and tricuspid valves, and was with coumarins. Her 6th pregnancy was uneventful, with no cardiovascular decompensation and delivered a healthy baby girl, weighing 1,700 g. without congenital malformations. We discuss here, her medical management during and after pregnancy as well as, the factors influencing an optimal result for both, mother and baby. PMID- 7789850 TI - [Scuba diving and pregnancy. A case report and review of the literature]. AB - The number of women in childbearing age participating in SCUBA dividing is increasing. Some dives during first trimester before pregnancy is confirmed. The preoccupation of both parents, is that the child could have any damage in the embryonal stage. This is a review of the literature and we present one case of a patient 28 years old with one immersion of 25 meters, at 28 days of gestation. The child did not present any congenital deformity at birth and his growth and development in the eighteen months have been normal. PMID- 7789852 TI - [Modified sling operation: institutional experience]. AB - We report the retrospective experience in the treatment of six patients with recurrent or severe stress urinary incontinence or low urethral pressure. They were treated with sling modified procedure with polytetrafluoroethylene (Gore Tex); in the National Institute of Perinatology (INPer) at 1992-1994. The morbidity was highest, the patients in the post operatory present detrusor instability, voiding problems and tissue reaction to polytetrafluoroethylene. The patients are continent in the actuality. They were observed by 8-32 months. This surgery is easy to make and not required of more experience than the necessary for realizing the cysto-urethropexy with needle, but, the selections criteria must be carefully analyzed. PMID- 7789854 TI - [HELLP syndrome. 7-year experience at the National Institute of Perinatology]. AB - We studied 36 patients with Hellp syndrome and her newborn during seven years in the National Institute of Perinatology (INPer). The objective of this study is show the epidemiology and clinic features, unite diagnostic criteria and classification, furthermore establish morbidity and mortality maternal and perinatal. The 44.6% (16/36) was type I, and 55.6% (20) was type II. The average of pregnancies was 3. The 38.9% (14/36) received regular prenatal control. Both types were more common in patients with preterm pregnancies, between 28-36 weeks. The patients with severe preeclampsia and eclampsia were more common. The cases with type I had more complications and stayed on hospital more time. The maternal mortality was 5.55%. Perinatal outcomes were unsatisfactory, with high incidence of asphyxiated newborn. The newborn of patients with type I had more severe complications and stayed more time on the hospital. The perinatal mortality was 32.43%. PMID- 7789853 TI - [Urinary retention secondary to surgical treatment of stress urinary incontinence]. AB - A retrospective, descriptive study at the National Institute of Perinatology (INPer), was carried out. 401 records of patients with stress urinary incontinence who underwent surgical treatment, were reviewed. The objective of this study was to know the urinary retention rate. Urinary retention was present in 103 of 401 patients (25.68%). In modified Pereyra's procedure it was present in 67 of 195 (34.35%); in modified Burch's procedure, in 25 of 131 (19.08%); in Kelly's procedure in 9 of 70 (12.85%) and in 2 of 5 patients with sling procedure with polytetrafluoroethylene (Goretex). The problem of urinary retention was observed more frequently in vaginal surgery (modified Pereyra procedure and/or sling procedure). PMID- 7789851 TI - [Feasibility study: concurrent 13-cis-retinoic acid, alfa-2a interferon and radiotherapy in the treatment of 23 patients with advanced cervix uteri epidermoid carcinoma]. AB - The important therapeutic activity of 13-cRA and IFN-alpha-2a in carcinoma of squamous cells, cervical, without previous treatment, is confirmed. An unexpected result was the early toxicity of the biologic agents on the colon mucosa when they are combined with radiotherapy. PMID- 7789855 TI - [Skin endometriosis in abdominal scar after cesarean section. Case report and review of the literature]. AB - Scan endometriosis is a rare entity, commonly related after operation on the uterus or uterine tubes or a laparotomy procedure or other no pelvic surgical procedure, when transplantations of endometrial fragments were shed into the peritoneal cavity. We present a case of a 31 year woman, who had the clinical and histopathological diagnosis of scar endometriosis following cesarean section, treated with local surgical excision of the abnormal tissue, with a satisfactory response. And a review of world literature, was done. PMID- 7789856 TI - [Evaluation of carbohydrate metabolism in women with previous gestational diabetes mellitus]. AB - 70 women with previous (1983-1993) history of gestational diabetes mellitus (GDM) were examined in order to assess their present carbohydrate metabolism. The through examination together with oral glucose tolerance test (OGTT) according to WHO were performed. Also the level of glycosylated hemoglobin HbA1c was measured. The following risk factors were analysed: obesity; arterial hypertension; family history of diabetes; number of past pregnancies; time that passed since the pregnancy with GDM; trimester in which GDM was diagnosed. In result 54% of all subjects were diagnosed as having diabetes mellitus, 19% had impaired glucose tolerance (IGT). The presence of diabetes or IGT significantly correlated with the number of past pregnancies, observation time and indirectly with family history of diabetes. Using both measurements of fasting blood glucose and glycosylated hemoglobin enables to diagnose nearly 80% of diabetes following GDM and as a diagnostic method is worth recommending for screening. Women who had GDM should be subjected to control examinations towards diabetes mellitus at least once a year. PMID- 7789857 TI - [Evaluation of the influence of placental localization on qualitative estimation of waveforms of blood flow velocity in uterine and arcuate arteries in third trimester physiologic pregnancy]. AB - We presented in our study methods and results of blood flow measurements with Doppler ultrasound in uterine and arcuate arteries in relation to localization of placenta in physiological pregnancy. We performed examinations in 154 pregnant women with pregnancy age of 32-42 wk. On the basis of qualitative analysis of blood flow waveforms we discovered the difference in the blood flow in utero placental compartment in relation to placental localization and we proved that this change takes place in uterine as well an in arcuate arteries. PMID- 7789858 TI - [Fluoride in the organism of mother and fetus. II. Fluoride cumulation in the organism of the fetus]. AB - The authors present the results of measuring the content of fluoride, calcium and phosphates performed on material comprising 66 thigh bones of human fetus in 4 age groups. In the studies the division into epiphysis and metaphysis parts was taken into consideration. A prepared complication furnishes the ratios of calcium to fluoride and calcium to phosphates in epiphysis and metaphysis parts, as well as ratio of calcium in epiphysis to calcium in metaphysis parts of the studied bones in the respective age groups. It has been disclosed that the increasing fluoride cumulation in fetal bones is a signal that the human organism is likely to be exposed to fluorine action already during the fetal life period. The fluoride content in thigh bones of fetus does not correlate with the content of calcium and phosphates, which may be evidence that there is a lack of significant influence of the determined fluoride content on the mineralization process taking place in bones at this period of life. PMID- 7789859 TI - [Evaluation of the effect of oxytocin use for labor induction on frequency of occurrence and severity of neonatal jaundice]. AB - Authors conducted analysis of effect of method used (which consisted of use of oxytocin, vit B, oestradiol) for labour induction on frequency of occurrence and severity of neonatal jaundice on 3rd day of neonatal life. Analysed material consisted of 1154 deliveries between the years 1990 to 1992 in IInd Department of Obstetrics AM Wroclaw. Only completely physiological pregnancies qualified for analysis. The above mentioned sum of analysed deliveries was divided into 2 groups. Ist group consisted of 801 normal deliveries without any oxytocin use 2nd group consisted of 353 normal deliveries during which i.v. oxytocin drip was used either for induction of labour or to intensify uterine contraction during labour. Evaluation of the above data do not show significant increase in cases with hyperbilirubinemia in group with labour induction (7%) in comparison with deliveries without oxytocin use (5%). Moreover eliminating from the analysis cases of jaundice with normal bilirubin level (12 mg%), I degree jaundice, the actual count of cases of hyperbilirubinemia in group without oxytocin use in 26 (3.24%) and in group with oxytocin use is 13 (3.67%) cases (Tab. IV) which is not a significant difference and does not permit us to conclude that oxytocin use for labour induction is responsible for increased frequency of neonatal hyperbilirubinemia. PMID- 7789860 TI - [The concentration of n-terminal propeptide of type III procollagen in umbilical cord serum--biochemical marker of newborn maturity]. AB - The concentration of N-terminal propeptide of type III procollagen (PIIINP) in umbilical cord serum was estimated in preterm and term newborns. The mean concentration of PIIINP was significantly higher in preterm infants, despite their lower body mass. This indicates higher rate of collagen biosynthesis in early gestation. The highest PIIINP were found among the most immature infants, which suggest the usefulness of PIIINP as an biochemical marker of newborn maturity. PMID- 7789861 TI - [CO2 laser in treatment of uterine cervix dysplasia in women with infertility]. AB - The authors presented use of carbon dioxide laser in treatment of dysplasia of the uterine cervix in women with malreproduction. Between November 1991 and September 1993 in the Department of Reproduction, Institute of Gynecology and Obstetrics, Academy of Medicine, Poznan the CO2-laser vaporisation in 21 women was done. In 19 patients the healing was achieved. In two of 21 women in control examination CIN was diagnosed. They were treated with electroconisation. In control examination no signs of dysplasia in all women were observed. The patients are still under control in our department. PMID- 7789862 TI - [Beeswax pessary in conservative treatment of uterine prolapse]. AB - The own method of uterine prolapse treatment with the use of beeswax pessary is presented. The described method is applied in cases where general health conditions do not allow to perform the surgery. The study revealed that the beeswax is a good material to make a vaginal pessary. It's great plasticity allows individual modelling in compliance with anatomical conditions of treated patient. That provides the proper stability of uterine position. The risk of possible urinary stress incontinence due to uterine reposition is also diminished. PMID- 7789863 TI - [Transfer RNA (tRNA) in primary and metastatic endometrial cancer tissue]. AB - Two dimensional polyacrylamide gel electrophoresis of 3' end labeled total tRNA from primary and secondary (metastatic) endometrial cancer was used to obtain mapping of isoacceptors. In tRNA from primary tumor 87 isoacceptors were found whereas in metastatic cancer only 52 spots corresponding to isoacceptors were detected. Normal myometrial tRNA used as a control contained 51 isoacceptors. The isoacceptors specific for neoplasia were observed in both cancer tRNAs. PMID- 7789864 TI - [Breast cancer in women under the age of 35]. AB - A retrospective analysis of a group of 102 women younger than 36 years is reported. All patients were treated initially only surgically by Halsted or Patey mastectomy. Disease-free 10-year survival was noted in 39.2% of the patients. The effectiveness of the treatment proved to be the same in the group of women under and over the age 35. For all patients with breast cancer, despite their age, identical prognostic factors were observed. PMID- 7789865 TI - [Combined calculation of dosage for brachytherapy and external beam therapy in radiation treatment of cervix cancer]. AB - In this paper authors present complex doses of ionizing radiation from brachytherapy and external beam therapy. Doses were determined on Computerized Planning System--Target 2 plus for patients with cancer of cervix. PMID- 7789866 TI - [Unsuccessful pregnancies in a genetic carrier of translocation 46,XX,t(4;5)(p11;q14)]. AB - Authors presents 36-year old female patient with three spontaneous abortions as a result of carrier state of balanced reciprocal translocation. This chromosome anomalies has been classified like the translocations with the double risk of unbalanced fetal karyotype++. The zygote can be normal, trisomic for part of a chromosome or monosomic for part of a chromosome. PMID- 7789867 TI - Neurophysiological evaluation of motor damage after ischaemic stroke. PMID- 7789868 TI - P3 components evoked by unilateral and bilateral somatosensory stimulation: normative data for the study of neglect syndrome. AB - Latency and amplitude of an "odd-ball" somatosensory P3 component evoked either by unilateral or bilateral somatosensory target stimulation, were measured in 15 healthy right-handed subjects (age range 42-79 years) in order to obtain normative data useful for studying the neglect syndrome. The bilateral stimulation protocol was designed to investigate the tactile extinction phenomenon. P3 waves were recorded from nine electrodes. A three-way Anova showed that mean P3 latency on the whole scalp following unilateral stimulations, regardless of side (i.e. right or left stimulations), was significantly longer than that observed after bilateral stimulation. Both "early" and "late" peaks were usually observed in P3 complex. The bilateral modality stimulation showed a more evident "early" peak than the two unilateral stimulations. No significant mean P3 amplitude differences were observed on the whole scalp between bilateral and unilateral stimulations. No significant amplitude differences were observed either for the right or the left hemisphere. The reported latency decrease in the bilateral target stimulation may be a valuable cue for studying possible modifications in patients affected by neglect. PMID- 7789869 TI - Sensitivity and specificity of the EEG versus CT in acute cortical and subcortical stroke. AB - 122 patients with acute stroke were examined in order to demonstrate the sensitivity and the specificity of EEG versus CT findings, in distinguishing cortical from subcortical lesions. To do this the electroencephalographic diagnosis performed by two different electroencephalographers was compared with the neuroimaging diagnosis. The results showed a sensitivity of 77% and a specificity of 75%. Furthermore, the EEG findings can also provide physiopathological data, in that the cortical lesions are likely to be due to embolism, while the subcortical lesions are more likely to be due to the pathological process of the intracerebral blood-vessels and the lesions of the watershed territories to hemodynamic phenomena. PMID- 7789870 TI - Charles Edouard Brown-Sequard. PMID- 7789871 TI - Thalamic regulation of epileptic spike and wave discharges. AB - Idiopathic generalized epilepsy is characterized by the spontaneous occurrence on the electroencephalogram of bilateral synchronous spike and wave discharges that involve the entire cortical mantle from the very onset. A central role in cortical synchronization is played by the thalamus, and in particular by the reticularis thalami nucleus, which is regarded as the pacemaker structure for the rhythmic cortical oscillations called spindle activity. Several studies have suggested that the network mechanisms which underlie spindle generation can also account for spike and wave discharges. Experimental investigations on genetic animal models of generalized epilepsy, in which seizures occur spontaneously in the absence of any inductive agent, confirmed that the thalamo-cortical system is involved in spike and wave discharge generation. According to these studies a genetically determined dysfunction in reticularis thalami neurons may alter the electroresponsiveness of the developing thalamo cortical system and cause a persistent state of abnormal excitation. PMID- 7789872 TI - Adjuvant postoperative radiation: what size target? PMID- 7789873 TI - Comparison of a novel redox dye cell growth assay to the ATP bioluminescence assay. AB - Antisense oligodeoxynucleotides (ASOs) are being studied with increasing frequency to determine their potential role as anticancer drugs. The overwhelming majority of this research continues to be done in vitro. Reliable and accurate determination of cell proliferation and/or inhibition, therefore, is essential for the production of meaningful results. The Alamar Blue assay, a colorimetric/fluorometric redox dye assay, was recently marketed by Alamar Biosciences (Sacramento, CA). In order to determine a potential role for this assay in ASO research, it was extensively tested on ovarian cancer cells in culture under a variety of conditions including uninhibited cell growth, cell kill with cytotoxic chemotherapeutic agents, and growth inhibition with ASOs. Results were compared directly with the ATP bioluminescence assay. We conclude that the Alamar Blue assay correlates poorly with the ATP assay, and it should be used only as a rapid preliminary screening assay. The ATP bioluminescence assay should continue to be considered as the standard in this setting. PMID- 7789875 TI - Complete inhibition of human ovarian cancer xenografts in nude mice by suramin and cis-diamminedichloroplatinum(II). AB - In this study, we have determined the adjuvant effects of suramin to cis diamminedichloroplatinum(II) (CDDP) on human ovarian cancer (KF) cell growth in vitro and in vivo. Suramin inhibited the ovarian cancer cell proliferation in vitro in a dose-dependent manner between 10 and 80 microM, showing the IC50 of 29 microM. From analysis of flow cytometry (FCM), suramin seemed to be a blocker of G2-M phase of the cell cycle. From the results of the isobologram, suramin appeared to have additive and somewhat synergistic effects on antitumor activity of CDDP. When 5 x 10(5) KF cells were inoculated sc into the right flank of nude mice, 8 of 10 mice formed solid tumor at 4 weeks. When 2 mg/kg CDDP was administered ip every week, the 80% tumor formation was prolonged to 10 weeks. Treatment with 5 and 10 mg/kg suramin decreased the formation rate of palpable tumor to 50 and 30%, respectively. When CDDP was followed by 5 or 10 mg/kg suramin, the tumor formation rate was 20 or 0%. On the other hand, if suramin was followed by CDDP, the tumor formation was not observed in any mouse during the experimental period. These results suggest that suramin may provide a new strategy for treatment of refractory ovarian carcinoma. PMID- 7789874 TI - A trial of lobaplatin (D-19466) in platinum-resistant ovarian cancer. AB - Long-term survival in epithelial ovarian cancer remains problematic despite multimodality therapy. A fundamental difficulty is the development of tumor resistance to platinum compounds. Analogs have been developed that demonstrate activity in platinum-resistant cell lines both in vitro and in vivo. Lobaplatin (D-19466), a third-generation compound, demonstrates significant activity in carboplatin and cisplatin-resistant cell lines. Lobaplatin was given to 17 assessable patients with platinum-refractory ovarian cancer. The drug was initially administered at a dose of 50 mg/m2 but was later reduced to 40 mg/m2 because of excessive thrombocytopenia. Nine patients required red cell transfusions during therapy. Cycles were repeated every 21-35 days (median cycle length 28 days). No objective responses were observed. Lobaplatin has no activity in platinum-resistant epithelial ovarian cancer. PMID- 7789876 TI - Evidence for tight coupling of gonadotropin-releasing hormone receptors to phosphatidylinositol kinase in plasma membrane from ovarian carcinomas. AB - Gonadotropin-releasing hormone (Gn-RH) analogs inhibit ovarian cancer cell proliferation in vivo and in vitro. To examine whether Gn-RH receptor (Gn-RHR) mediates direct antiproliferative effects, we attempted to determine inhibitory regulation by Gn-RH of phosphatidylinositol (PtdIns) kinase activity, known to stimulate mitogenic response, in plasma membranes isolated from ovarian carcinoma samples. Ovarian carcinomas surgically removed and cloned cell line SK-OV3 had been screened for Gn-RHR expression prior to plasma membrane isolation. PtdIns kinase activity was measured as phosphorylation of exogenous substrate PtdIns by the purified plasma membranes. Incubation of the plasma membranes isolated from Gn-RHR-positive specimens with [gamma-32P]ATP and PtdIns caused [32P]phosphate incorporation into PtdIns phosphate (PtdInsP) in a time-dependent manner. Concomitant exposure of the membrane preparations to Gn-RH analog buserelin (1 microM) led to a 70% inhibition of the PtdInsP production, when compared to control. After 10 or 15 min of an initial incubation, the addition of analog resulted in similar suppression of PtdIns phosphorylation. This inhibition was dependent on the buserelin dose, and a half-maximal effect occurred at a concentration 0.1 to 1 nM of buserelin. Degradation of the produced PtdInsP in the plasma membranes was not affected by the Gn-RH analog. Similar inhibition of PtdIns kinase activities was observed in membranes prepared from cells that had been pretreated with buserelin (1 microM) for 48 hr prior to assay. These findings demonstrate that PtdIns kinase activity is suppressed by Gn-RH analog in plasma membrane isolated from GnRHR-expressing ovarian carcinomas, suggesting a tight coupling of Gn-RHR to PtdIns. The inhibition of membrane-associated PtdIns kinase by Gn-RHR occupancy may mediate the antimitogenic action of the hormone on human ovarian carcinomas. PMID- 7789877 TI - Fertility therapy in the setting of a history of invasive epithelial ovarian cancer. AB - A link between fertility drugs and epithelial ovarian cancer has been suggested by at least one case-control study, and by multiple case reports of such tumors developing following fertility drug therapy. We report the case of a woman with stage IC grade 1 mucinous epithelial ovarian cancer who died of recurrent disease shortly after receiving gonadotropin therapy for ovulation induction. The patient was initially treated with a staging procedure, unilateral salpingo-oophorectomy, and 3 courses of cytoxan and carboplatinum. Over the next 3 years she underwent 2 cycles of ovulation induction with exogenous gonadotropins. Five months after the second cycle, the patient presented with a bowel obstruction and extensive recurrence of disease. Two months later she died despite extensive surgical debulking, and cis-platinum and Taxol chemotherapy. Although a causal relationship between fertility therapy and ovarian cancer has not been established, this case report suggests ovulation induction may be inadvisable in a woman with a prior diagnosis of invasive epithelial ovarian cancer. PMID- 7789878 TI - Paraneoplastic retinopathy associated with uterine sarcoma. AB - We present the first reported case of cancer-associated retinopathy with uterine sarcoma. A 65-year-old woman presented in August 1990 with loss of vision, photophobia, and visual field restriction. Antiretinal antibodies were elevated. A diagnosis of cancer-associated retinopathy was made, the patient was started on prednisone, and a workup for malignancy was initiated. The patient was found to have uterine sarcoma. She underwent an extrafascial hysterectomy with bilateral salpingo-oophorectomy followed by eight courses of chemotherapy (carboplatin and cyclophosphamide). After that, the patient's vision improved, her visual field stabilized. She was doing well when last seen, in July 1994. The literature regarding cancer-associated retinopathy and paraneoplastic syndromes associated with gynecologic malignancies is reviewed. PMID- 7789879 TI - Gonadoblastoma with dysgerminoma in one ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the contralateral ovary in a girl with 46XX karyotype. AB - A case of gonadoblastoma with dysgerminoma in the left ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the right of a 10-year-old girl is reported. Her karyotype was 46XX, normal female type. A case of a gonadoblastoma without a Y chromosome is very rare. Furthermore, the prognosis for gonadoblastoma accompanied by germ cell tumors other than dysgerminoma was very poor in the past, but the patient remains well 25 months after the first operation. PMID- 7789880 TI - Primary jejunal adenocarcinoma masquerading as a primary ovarian malignancy. AB - Primary adenocarcinoma of the jejunum which accounts for only approximately 3% of all gastrointestinal tract malignancies, is distinctly unusual. Ovarian metastasis from a jejunal cancer is extremely rare. It has significant therapeutic and prognostic implications to differentiate primary ovarian carcinoma from metastatic disease to the ovary. A 49-year-old Japanese woman presented with intermittent nausea, vomiting, and palpable abdominal mass. Pelvic examination and imaging studies revealed a huge ovarian tumor, suspicious for malignancy. Upper GI series and barium enema were unremarkable. Exploratory laparotomy was done for presumed primary ovarian malignancy. Mucinous adenocarcinoma of the right ovary, measuring 25 x 18 x 12 cm, without other intraabdominal dissemination was found. Exploration of the upper abdomen revealed an annular constriction of the jejunum 30 cm distal to the ligament of Treitz. Partial jejunectomy with end-to-end anastomosis was done. Metastatic ovarian cancer from the primary jejunal adenocarcinoma was confirmed microscopically. Although small bowel malignancy is uncommon, small bowel follow-through examination or enteroclysis may be indicated in patients with positive stool for occult blood who have no abnormality in the upper gastrointestinal series and barium enema. In addition to the imaging studies, thorough exploration of the entire abdominal cavity is necessary at ceiliotomy in patients with ovarian malignancy to distinguish primary ovarian cancer from metastatic disease to the ovary. PMID- 7789881 TI - Secretory endometrial adenocarcinoma in a patient on tamoxifen for breast cancer: a report of a case. AB - Well-differentiated endometrial adenocarcinoma of the secretory type (FIGO Grade 1) with minimal myometrial invasion occurred in a postmenopausal patient on tamoxifen therapy 5 years after mastectomy for breast carcinoma. We believe that this is the first report of secretory carcinoma of the endometrium associated with tamoxifen use. This unusual pattern of low-grade endometrial carcinoma adds to the spectrum of uterine neoplasia associated with tamoxifen therapy. PMID- 7789882 TI - Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: clinicopathological and immunohistochemical study of two cases. AB - Clinicopathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of endometrioid type which may have arisen in the isthmus are presented. Hysterectomy specimens from two women, one 39 years of age and the other 64 years of age, showed the presence of endometrioid-type adenocarcinoma with minimal atypia and without back-to-back arrangement of the glands, which was consistent with a histological diagnosis of endometrioid MDA. However, the tumorous glands were most abundant in the isthmus, and extensively infiltrated into the cervical stroma, vagina, parametrium, and corpus in one case, and the tumor was confined to the isthmus in the other. Immunohistochemically, the tumorous glands were CEA-positive and vimentin-negative in both cases. p53 protein expression was found in one case. Histogenetic origin of MDA of endometrioid type is discussed. PMID- 7789883 TI - Regarding positive smears with normal colposcopy and the frequency of CIN. PMID- 7789884 TI - The influence of combination chemotherapy on antigen expression in ovarian cancer. AB - The best treatment results for advanced-stage ovarian cancer patients are obtained with cytoreductive surgery followed by combination chemotherapy. However, the 5-year survival rate of only 20% clearly shows a need for new treatment modalities. At present several modes of immunotherapy for cancer are being explored such as the use of monoclonal antibodies, bispecific antibodies, or specific cytotoxic effector cells, all making use of the presence of tumor associated antigens remaining, necessary for tumor cell recognition. The antigenic phenotype of human epithelial ovarian cancer after chemotherapy treatment is an important issue in planning potential immunotherapeutic strategies for ovarian cancer. Therefore, we compared the antigen expression in tumor specimens obtained during operation for primary epithelial ovarian tumors and tissue biopsies taken during second-look operations after the administration of combination chemotherapy. A total of 60 ovarian tumors, including 44 serous, 3 mucinous, 2 endometrioid, 1 clear cell, 6 mixed, 2 undifferentiated, and 2 granulosa cell tumors, was studied. Frozen sections of the tumor specimens were stained with 15 different monoclonal antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. The results showed only limited differences in antigenic expression in tumor tissue obtained before and after chemotherapy. Because antigen expression was not altered, immunotherapy making use of these antigenic determinants will not be hampered by prior chemotherapy. PMID- 7789885 TI - Parametrial interstitial brachytherapy for advanced or recurrent pelvic malignancy: the Harvard/Stanford experience. AB - In this study we evaluate the long-term efficacy and safety of transperineal interstitial implants for advanced pelvic malignancy. A total of 139 patients were treated at Stanford University Medical Center and the Joint Center for Radiation Therapy with transperineal template interstitial brachytherapy for locally advanced or recurrent cancers arising in the pelvic organs. Most patients received whole pelvis external beam irradiation to a median dose of 4200 cGy followed by an implant for a median duration of 48 hr to a median implant dose of 3000 cGy (range 600-6000 cGy). Complete follow-up was obtained for 91% of the patients. Median follow-up for survivors is 57 months (range, 10-173 months). The crude disease-free survival rate was 22% at 5 years. The 5-year crude local tumor control rate was 25%. No dose-response relationship could be demonstrated for tumor control or complications. There were no acute treatment-related deaths. Three late deaths were seen which were directly related to treatment. Major bowel complications requiring surgery were seen in 17% of patients without locally recurrent disease, and fistulas were reported in 4% of these patients. We conclude that template parametrial implant brachytherapy offers a modest chance of cure for women with locally advanced pelvic malignancy. However, this treatment causes significant late morbidity. PMID- 7789886 TI - MIB 1 immunostaining in stage I squamous cervical carcinoma: relationship with natural killer cell activity. AB - The aim of the study was to investigate the prognostic significance of estimating tumor cell proliferation in stage I cervical squamous carcinoma by analyzing MIB 1 immunostaining with respect to the lesion size, lymphatic spread, and clinical outcome. A possible relationship between MIB 1 index and natural killer activity was also discussed. The medical records of 34 patients with stage I squamous cervical carcinoma who had undergone primary radical surgery at the Institute of Gynecologic and Obstetrics, Ancona University, between 1988 and 1993, were recruited from our series of 57 consecutive cases and reviewed. Thirty-one patients were considered eligible for the study and evaluated for age, demographic characteristics, tumor histologic grade, tumor size, lymphatic spread, and adjuvant radiotherapy. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. The basal natural killer cell activity of peripheral blood lymphocytes was evaluated against K562 cell line and expressed in lytic units for each patient. The MIB 1 immunostaining was significantly related with tumor size (P = 0.001) and lymphatic spread (P = 0.009); in contrast, there was no relationship between grade of histologic differentiation and MIB 1 immunostaining. The Cox proportional hazards analysis showed a significant independent relationship between MIB 1 immunostaining and disease-free survival (P = 0.004). The analysis of natural cytotoxicity defined a significant inverse relationship between peripheral blood lymphocyte's natural killer activity and tumor MIB 1 immunostaining (r = -0.07, with P = 0.03). Our data defined the prognostic significance of tumor cell proliferation immunostaining, an interesting parameter correlated with the disease-free survival in locally advanced cervical carcinoma. The relationship between MIB 1 index and natural killer activity is interesting; natural cytotoxicity seems to be altered in the host with respect to the cervical carcinoma characteristics. PMID- 7789887 TI - Phase II study to evaluate the toxicity and efficacy of concurrent cisplatin and radiation therapy in the treatment of patients with locally advanced squamous cell carcinoma of the cervix. AB - Sixty patients presenting with poor prognosis squamous cell cancer of the cervix have been studied in a phase II clinical trial. Patients were treated with radiotherapy and concurrent cisplatin chemotherapy every 10 days. Treatment was well tolerated with all patients completing radiotherapy as prescribed. There was one case of grade 4 acute bowel toxicity. Significant late morbidity was acceptable for this group of patients being restricted to two cases (3.3%) of grade 4 toxicity to the bowel. Pelvic control rates of 78% have been observed. There have been no pelvic recurrences after 26 months, although recurrences beyond the pelvis have occurred up to 4 years later. Actuarial 4-year survival is encouraging at 60%. PMID- 7789888 TI - Long-term observation of patients treated by postoperative extended-field irradiation for nodal metastases from cervical carcinoma stages IB, IIA, and IIB. AB - Extended-field irradiation was administered to 72 patients after radical surgery for nodal metastases from cervical carcinomas at Stage IB (37 patients), IIA (6 patients), and IIB (29 patients) who were treated from 1981 to 1986. The 5-year disease-free survival rates (DFR) were significantly different between 61 squamous cell carcinomas and 11 nonsquamous cell carcinomas (72 versus 27%, P = 0.0051). In the 61 squamous patients, the DFR were 82% for 51 patients with resectable nodes and 20% for 10 patients with unresectable nodes (P = 0.0003). In the 51 patients with resectable nodes the DFR were 84% for Stage IB, 100% for Stage IIA, and 76% for Stage IIB. There were no significant differences among those categories subdivided by clinical stage, number of positive nodes, common iliac node metastasis, positive node laterality, depth of tumor invasion, parametrial extension, and menopause. These findings suggest that postoperative extended-field radiotherapy is effective in squamous cell carcinomas and that the prognostic values of these factors were decreased with high patients survival rates given by this combined therapy. PMID- 7789889 TI - Serum half-life of CA 125 during early chemotherapy as an independent prognostic variable for patients with advanced epithelial ovarian cancer: results of a multicentric Italian study. AB - This retrospective multicentric study assessed the prognostic value of the serum CA 125 assay and the common clinicopathological variables in 225 patients with advanced epithelial ovarian cancer. All of these patients had serum CA 125 > or = 35 U/ml before the first cycle of chemotherapy and had had serial antigen determinations during early chemotherapy. By univariate analysis pathological complete response rate was significantly related to stage, size of residual disease after first surgery, serum CA 125 before the first cycle and before the third cycle of chemotherapy, and serum CA 125 half-life. Multiple logistic regression showed that residual disease (P = 0.002), serum CA 125 half-life (P = 0.004), serum CA 125 before the third cycle (P = 0.004), and serum CA 125 before the first cycle (P = 0.03) retained a significant value in predicting second-look findings. By log-rank test survival was significantly related to stage, residual disease, tumor grade, serum CA 125 before the third cycle, and serum CA 125 half life. Cox proportional hazard model showed that residual disease (P = 0.0001), serum CA 125 half-life (P = 0.007), and tumor grade (P = 0.01) retained a significant value in predicting survival. In conclusion, serum CA 125 half-life during early chemotherapy was an independent prognostic factor for both the achievement of a pathological complete response and the survival of patients with advanced epithelial ovarian cancer. PMID- 7789890 TI - A correlation of cell cycle perturbations with chemosensitivity in human ovarian cancer cells exposed to cytotoxic drugs in vitro. AB - To test the association between cytotoxicity and in vitro cell cycle perturbations we systematically studied cell cycle perturbations after exposing human ovarian cancer cells to nine commonly used cytotoxic agents. Three principal patterns of cell cycle alterations were observed: a sequential S-G2/M block after exposure to the non-phase-specific agents cis-platinum, 4-hydroperoxy cyclophosphamide, and mitomycin C (Group I); an isolated G2/M block after exposure to the G2/M phase-specific drugs etoposide and vincristine and the non phase-specific agent doxorubicin (Group II); and an isolated S block following exposure to the S phase-specific agents 5-fluorouracil, methotrexate, and cytosine arabinoside (Group III). Overall, there was no direct correlation between the degree of cell cycle perturbations and chemosensitivity. However, when the three subgroups of non-phase-specific agents, S phase-specific agents, and G2/M-specific agents were analyzed separately, positive correlations between the magnitude of cell kinetic alterations and chemosensitivity were observed. Cell kinetic alterations appeared to precede cytotoxicity. PMID- 7789891 TI - Factors predicting response to chemotherapy and survival in patients with metastatic or recurrent squamous cell cervical carcinoma: a multivariate analysis. AB - Different regimens of chemotherapy have been proposed with contradictory results in patients with metastatic and recurrent cervical carcinoma: this seems mainly due to the lack of information about prognostic factors. This study was aimed at identifying significant factors predicting response to treatment and survival in 140 patients treated with chemotherapy for advanced, recurrent, or persistent squamous cell cervical carcinoma. Age, performance status, histologic type and grade, previous irradiation, interval from start of primary treatment and from irradiation, site of tumor, and therapeutic regimen were considered as possible predictors of response and survival in multivariate analysis. By multivariate analysis, only performance status and interval from irradiation (> 1 year) were significant in predicting response to treatment, whereas interval from first diagnosis, site of tumor, and response to treatment were significant in predicting survival. None of the polychemotherapy regimens significantly improved survival, despite a fourfold increase in the costs when compared to the least expensive monochemotherapy regimen. Ethical and economical concerns should be considered when proposing aggressive regimens to the patients. Factors such as site of tumor, performance status, and interval from first treatment should be considered as minimal requirements for correct evaluation of newly proposed regimens. PMID- 7789892 TI - Rising ovarian cancer mortality in the elderly: a manifestation of differential survival. AB - Ovarian cancer mortality among the elderly in developed countries is increasing. Using published United States mortality data, annual age-specific ovarian cancer mortality rates from 1951 to 1989 were determined for the over-60 age groups and compared to corresponding annual age group population sizes. Rising ovarian cancer mortality rates among the elderly in the United States from 1951 to 1989 were increasingly dependent, with increasing age, upon increasing age group population size. These findings suggest that differential survival, and its effect upon the surviving gene pool in an aging population, may account for some of the observed increase in ovarian cancer mortality rates among recent successive elderly cohorts. PMID- 7789893 TI - Carboplatin (CBDCA)-hexamethylmelamine (HMM)-oral etoposide (VP-16) first-line treatment of ovarian cancer patients with bulky disease: a phase II study. AB - Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be active against platinum-resistant epithelial ovarian cancer. On this basis a three-drug regimen including carboplatin (CBDCA) plus HMM and oral VP-16 was tested in previously untreated ovarian cancer patients with tumor size > 2 cm. Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses. CBDCA was administered i.v. on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC = 5). VP-16 was administered orally at the dose of 50 mg/m2 Days 1-14, HMM at the dose of 150 mg/m2 po Days 14-28. Therapy was repeated every 28 days for a total of 6 courses. In order to avoid severe leukopenia and delays in the treatment administration, G-CSF 5 micrograms/kg/day sc Days 8-14 (or until postnadir recovery of neutrophil count > 10,000/mm3) and Days 22-28 was administered. All patients were evaluable for toxicity. No treatment-related deaths occurred. Myelotoxicity was the main side effect. It was grade 3-4 in a total of 13/29(45%) patients. One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity. The actual delivered dose intensity was 89% of the planned dose. At the time of this analysis (April 1994) 26 patients are evaluable for response. Fifteen patients achieved a clinical complete remission and 9 a partial response for a 92% overall response rate. Fourteen patients accepted second-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21 63). At a median follow-up of 16 months 3 deaths have occurred. Only 2 patients with NED at second-look laparotomy have relapsed. We stopped the accrual since the 95% confidence interval of the pCR-rate observed exceeded 20%. This new first line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival. PMID- 7789894 TI - Pelvic exenteration for adenocarcinoma of the uterine cervix. AB - The objective of this study was to describe and compare the outcome of patients with recurrent adenocarcinoma versus squamous cell carcinoma of the uterine cervix who have been treated with pelvic exenteration. All patients undergoing pelvic exenteration for cervical adenocarcinoma from 1955 to 1989 were identified and a retrospective review was conducted. For these 35 patients, we identified 70 controls who had exenteration for squamous cell carcinoma and who were matched for node status, year of procedure, and type of procedure. No significant difference was noted between the control group and the adenocarcinoma group for size of recurrent tumor, status of margins, presence of hydronephrosis prior to exenteration, and the time elapsed from initial diagnosis to exenteration. The two groups were compared for survival and recurrence pattern. Median patient age was 47 years (range 22-70). All patients had prior pelvic radiotherapy. Thirty patients had total pelvic exenteration and 5 had anterior exenteration. There were 3 postoperative deaths (8.6%). Median survival was 38 months for the adenocarcinoma patients and 25 months for the squamous patients (P > 0.99). The overall survival between the two sets of patients was very similar (log rank P = 0.86). There were 23 postexenteration recurrences among the adenocarcinomas (22 in which the site is known) and 32 postexenteration recurrences among the squamous patients (30 with known site). For the adenocarcinoma patients, 14 of 22 had a distant recurrence versus 14 of 30 for the squamous patients (P = 0.27). Patients with central recurrence of cervical adenocarcinoma can be successfully treated with pelvic exenteration and have survival rates similar to squamous carcinoma. PMID- 7789895 TI - Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels. AB - The purpose of this study was to estimate the response rate, response duration, and survival of patients with advanced ovarian cancer treated with a 132-hr continuous infusion of high-dose calcium leucovorin in combination with five consecutive daily bolus doses of 5-fluorouracil (5-FU) and to correlate changes in CA-125 levels with clinical and radiologic assessment of disease progression. Forty-six heavily pretreated patients [median number of previous chemotherapy regimens, 2.5 (range 1-7)] with advanced ovarian cancer received 132-hr continuous infusions of calcium leucovorin (500 mg/m2/day) for 5 1/2 days, with daily bolus doses of 5-FU (370 mg/m2/day) for 5 days beginning 24 hr after initiation of the calcium leucovorin. Twenty-three patients had clinically measurable disease and 23 had evaluable disease; CA-125 levels were performed prior to each treatment course and after the final course of therapy. One of 42 patients had a partial response to combination chemotherapy (duration, 8.9 months); 16/42 had stable disease [median duration, 4.9 months (range, 2.4-9.0 months)]. Toxicity of combination therapy included mild myelosuppression and stomatitis, similar to previously reported toxicity profiles for the 5-FU and calcium leucovorin combinations. Sensitivity of CA-125 levels as a single indicator of disease progression was 55%. The combination of infusional high-dose calcium leucovorin and 5-FU has little activity in refractory ovarian cancer. CA 125 levels incorrectly predict clinical disease activity in about one-third of cases and should not be the sole criterion for determination of clinical response when evaluating chemotherapeutic efficacy in heavily pretreated patients. PMID- 7789897 TI - A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection. AB - The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access. PMID- 7789898 TI - [Thromboembolism complications in gynecology and obstetrics. Prevention, diagnosis and therapy]. PMID- 7789896 TI - Adenomyosis in postmenopausal breast cancer patients treated with tamoxifen: a new entity? AB - Between September 1, 1989 and October 31, 1994, 173 postmenopausal breast cancer women on tamoxifen treatment were followed up in the authors' institutions. During this period, 14 (8.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. Eight (57.1%) were found to have adenomyosis, of whom one had a large fundal adenomyotic lump and the other seven patients had two to four small microscopic foci of adenomyosis. In this study, the rate of adenomyosis described among those postmenopausal breast cancer patients treated with tamoxifen is nearly three to four times higher than the rate reported in the literature for pre- and postmenopausal women. There is no previous reported increased incidence of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Thus, it is suggested that the prolonged and unopposed estrogen-like stimulation by tamoxifen may play a causal role rather than be a casual factor in the development of this pathologic entity. PMID- 7789899 TI - [Indications for intensive monitoring during and after extensive gynecologic interventions]. PMID- 7789900 TI - [Perioperative risk factors from the forensic viewpoint and patient education]. PMID- 7789901 TI - [Hamartoma of the breast. 2 case reports]. PMID- 7789902 TI - [Patient education by the physician--burden or opportunity?]. PMID- 7789903 TI - [The effect of extensive surgical interventions on cellular immune response]. PMID- 7789904 TI - [Cardiac risk assessment in surgical medicine]. PMID- 7789906 TI - [Postoperative psychiatric complications with special reference to gynecologic interventions]. PMID- 7789905 TI - [Gastrointestinal diseases in perioperative assessment with reference to gynecologic interventions]. PMID- 7789907 TI - Improved techniques for first-trimester fetal reduction using simultaneous abdominal and transvaginal ultrasonographic guidance. Preliminary report. AB - Simultaneous transabdominal injection of potassium chloride (KCl) assisted by transvaginal ultrasonographic guidance was evaluated in 5 patients who conceived due to various assisted reproductive techniques and ovarian stimulation. All 5 underwent first-trimester fetal reduction for multiplicity of high-order pregnancies. Four sets of triplets were reduced to twin, and 1 twin pregnancy was reduced to a singleton. Less than 2 ml of 2 mEq/ml KCl per fetus was needed for each case. No fetal or maternal complications nor technical failure attributable to the procedure were recorded. All pregnancies were delivered > or = 35 weeks of gestation. Transabdominal fetal reduction using simultaneous transvaginal ultrasonographic guidance for selective feticide combines the benefits of both the transabdominal and transvaginal approaches, mainly in selected cases in which some experts prefer the abdominal route, but find it technically difficult to practice. Further experience is needed to confirm our encouraging preliminary results before drawing any definitive conclusions. PMID- 7789908 TI - Fetal pleural effusion: the risk of fetal trisomy. AB - Our objective was to review the association between fetal pleural effusion (FPE) and fetal aneuploidy. We conducted a retrospective survey of pregnant women who presented to our ultrasonographic unit between 1990 and 1991, and in whom the diagnosis of FPE was reached. All fetuses had karyotype investigation and a complete ultrasonographic search for associated anomalies. Six cases of FPE were identified. Trisomy 21 was found in 2 (33%). The English literature was reviewed and an additional 147 cases with FPE were collected, among them 6 cases of trisomy 21 and 1 of monosomy 45X. In this accumulated series the risk of aneuploidy in a fetus with an incidental finding of FPE was 5.8% (9 of 153), thus warranting a karyotype study. PMID- 7789910 TI - Relationship between granulocyte elastase levels and perinatal infections. AB - This study was conducted in order to investigate the usefulness of granulocyte elastase levels as predictive factors in the onset of perinatal infections. The subjects were 41 patients who delivered within 48 h after amniocentesis after giving their informed consent. The relationship between cervical granulocyte elastase (Cx-E), serum C-reactive protein (CRP) and amniotic fluid granulocyte elastase (Af-E), and placental infections and neonatal infections was comparatively investigated. In some cases, gastric juice granulocyte elastase in neonates (Gj-E) was measured, and the correlation by site was investigated. Elastase levels were not used as a management protocol. In predicting neonatal infections, diagnostic efficacy (sensitivity x specificity) of placental infections (0.97) and abnormal Af-E (0.79) were superior to those of abnormal Cx E (0.40) and abnormal CRP (0.49). There was no correlation between Cx-E and Af-E or between Cx-E and Gj-E; however, a very close correlation was noted between Af E and Gj-E. In predicting abnormal amniotic fluids, Cx-E (> or = 1.2 micrograms/ml) + CRP (> or = 1.0 mg/dl) had the highest diagnostic efficacy with 0.58. These findings demonstrate that Af-E is a good index for predicting the onset of neonatal infections. In predicting abnormal amniotic fluid, it might be advisable to consider amniocentesis in order to diagnose intrauterine infections, when both Cx-E and CRP show abnormal levels. PMID- 7789909 TI - Cyclo-oxygenase distribution in human placenta and decidua does not change with labour after term or preterm delivery. AB - Our objective was to determine, in an immunohistochemical study, the distribution of cyclo-oxygenase in placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 13); spontaneous term labour at 37-42 weeks' gestation (n = 11); preterm caesarean section at less than 34 weeks' gestation for pre-eclampsia or intrauterine growth retardation (n = 8); elective term caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 7). Within the placental basal plate cyclo oxygenase was localised in decidual stromal cells, extravillous trophoblast, and the apical border of villous syncytiotrophoblast, both before and after labour, regardless of gestational age. Within the placental membranes, decidual stromal cells showed intense cytoplasmic cyclo-oxygenase labelling and the chorion laeve strong membrane-associated cyclo-oxygenase reactivity before and after labour, regardless of gestational age. The amnion showed a heterogeneous staining pattern. After labour at term there was either positive cytoplasmic (5/10) or apical staining (5/10). Cyclo-oxygenase was demonstrated in an apical distribution in only 50% of the other subject groups. Cyclo-oxygenase is present in both decidua and placental tissues prior to the onset of labour at term. Demonstration of decidual and trophoblastic cyclo-oxygenase in both preterm and term subjects suggests that differential availability of cyclo-oxygenase is unlikely to be important in preterm delivery. Research into the withdrawal of inhibition or increased substrate availability is most likely to shed light on the signal pathways involved in the onset of labour, regardless of gestation. PMID- 7789911 TI - Chronic hypertension in gestational diabetes: influence on pregnancy outcome. AB - Our objective was to study the influence of chronic hypertension on pregnancy outcome in women with gestational diabetes (GDM). 418 women with GDM (30 with chronic hypertension and 388 nonhypertensives) were referred to our diabetes in pregnancy program. All patients were followed and assessed biweekly until delivery. When hypertensive GDM women (n = 30) wer compared to all nonhypertensive GDM (n = 388), there were significant (p < 0.05) differences in mean maternal age (34 +/- 4.1 vs. 30 +/- 4.6 years), maternal weight (90 +/- 21.2 vs. 70.6 +/- 14.9 kg) and gestational age at delivery (38.5 +/- 1.2 vs. 39.6 +/- 1.2 weeks). The mean birth weight for the hypertensive GDM group was significantly higher than that of the nonhypertensive GDM (3,360 +/- 578 vs. 3,293 +/- 581 g; p < 0.05). The frequencies of LGA (23.3 vs. 9.8%) and induction prior to onset of spontaneous labor were significantly (p < 0.05) higher in the hypertensive GDM group when compared to the nonhypertensive GDM. There were no differences with respect to the average blood glucose and frequencies of SGA deliveries. However, when the 30 hypertensive GDM pregnancies were compared to a control group of 60 nonhypertensive GDM women matched for age, weight and height, the only significant difference was a higher rate of inductions of labor (36.7 vs. 6.6%, p < 0.05) in hypertensive diabetic women. There were no significant differences in the incidence of LGA, low Apgar scores and SGA deliveries when hypertensive GDM were compared to nonhypertensive GDM women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789912 TI - Longitudinal Doppler ultrasonographic assessment of alterations in regional vascular resistance of arteries in normal and growth-retarded fetuses. AB - The objective of this longitudinal study was to evaluate alterations in regional vascular resistance of arteries with advancing gestation in normal and growth retarded fetuses. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were performed on 13 normal and 7 growth-retarded fetuses, ranging from 15 to 40 weeks menstrual age. The pulsatility index was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery and umbilical artery, respectively. Optimal models for these pulsatility index values were determined by regression analysis. A normal range of the pulsatility index for each artery generated in the normal fetuses. In the middle cerebral artery, the models showed a parabolic pattern during pregnancy in the two groups and the predicted pulsatility index values in growth-retarded fetuses were always lower than those in the normal fetuses, especially late in pregnancy. In the renal artery, the predicted pulsatility index values in growth-retarded fetuses were higher than those in normal fetuses near term. In other arteries, the predicted pulsatility index values showed their own specific patterns and there were no significant differences in predicted pulsatility index values in the two groups. In conclusion, alterations in regional vascular resistance of arteries with advancing menstrual age occur evidenced in both normal and growth retarded fetuses. PMID- 7789913 TI - A case-control study on post-caesarean endometritis-myometritis in Mozambique. AB - Post-caesarean endometritis-myometritis (PCEM) was diagnosed in 49 Mozambican women. They were compared with 47 control women without signs of PCEM after caesarean section. The patients and controls were matched for age, parity and days post partum. Features of the socio-economic background and of past and current obstetric history were registered. Endocervical, intracavitary and blood cultures were carried out. Screening for syphilis seropositivity and HIV-1 and HIV-2 antibodies was performed. Socio-economic and obstetric background factors were similarly distributed in cases and referents, though previous caesarean section was less frequent among cases than among referents (OR 0.12). Moderate high-risk factors in existing antenatal card tended to be more frequent among cases than among referents (OR 3.29). Microbiological findings indicated more anaerobes in the vagina, in the endocervix and in the uterine cavity, though the differences only approached significance. It is concluded that women with PCEM in the setting studied expose few characteristic background features discriminating them from women with uneventful post-caesarean outcome. Further research efforts should be directed towards case-control studies with focus upon surgical factors and on a more comprehensive microbiology and serology approach. PMID- 7789914 TI - Postoperative adhesion formation following ovarian reconstruction with fibrin glue in the rabbit. AB - To compare postoperative adhesion formation following ovarian reconstruction with fibrin glue or the microsurgical suturing technique, an experimental study was performed on sixteen adult female rabbits. While left ovaries were reapproximated with 6-0 coated polyglactin using a microsurgical technique, right ovaries were reconstructed with fibrin glue following ovarian bisection. Four weeks later, second-look laparotomies were performed to evaluate the adnexal adhesions. These were scored according to the American Fertility Society classification. Mean adnexal adhesion scores were 8.2 +/- 2.3 in the sutured ovary and 5.0 +/- 1.1 in the glued ovary (p > 0.05). Ovarian reconstruction with fibrin glue does not reduce postoperative adhesion when compared with the usual suturing technique. PMID- 7789915 TI - The reproducibility of the Doppler ultrasound measurement of uterine artery vascular resistance. AB - The intra- and interobserver variation in Doppler ultrasound measurements of uterine arteries (UA) and the variation of pulsatility index (PI) in UA in successive menstrual cycles in the same patient was studied. The intra- and interobserver variability of measurements was similar. In all three series the difference between two measurements was smaller with lower PI values. Cycle dependent changes, biological variation and random measurement are foremost in causing variability and no systematic error was evident. Doppler ultrasound measurements from UA can be used when patient groups are compared, but in the case of an individual patient, large limits of agreement must be borne in mind. PMID- 7789916 TI - Direct effect of danazol on the DNA synthesis and ultrastructure of human cultured endometrial stromal cells. AB - The direct effect of danazol on the DNA synthesis and ultrastructure of human cultured endometrial stromal cells was studied. The analysis of the [3H]thymidine incorporation in the endometrial stromal cells cultured for 10 days indicated that the DNA synthesis was inhibited in a dose-dependent manner by danazol and testosterone, but not by medroxyprogesterone. The effect of 10(-7) M of danazol was blocked by cyproterone acetate, but RU-486 did not show any influence. The observation of the ultrastructure of the cultured cells revealed that 10(-7) M of danazol increased cytoplasmic lysosomes; however, 10(-5) M of danazol destroyed cell organelles and cytoskeleton resulted from the cell death. These results indicated that the biological effects of danazol were mainly mediated by androgen receptors, and 10(-5) M of danazol exhibited the toxic effect on the endometrial stromal cells. PMID- 7789917 TI - Serum levels of relaxin during the menstrual cycle and oral contraceptive use. AB - Serum relaxin levels were analysed in 12 healthy women every other day during the menstrual cycle and during a second cycle on oral contraceptives. Relaxin levels in 7 women with posterior pelvic and lumbar pain were also measured. Relaxin was detected during both the follicular and luteal phases of the menstrual cycle in some of the healthy women. Serum levels were further increased during the use of oral contraceptives. Oestradiol levels in the untreated women correlated to the relaxin levels. Women with posterior pelvic and lumbar pain had higher relaxin levels than did healthy women, a finding that needs to be further explored. Our data indicate the existence of sources for relaxin production other than the corpus luteum in the non-pregnant woman. Endogenous and exogenous oestrogens may stimulate the production of relaxin. PMID- 7789918 TI - Transvaginal ultrasonographic morphology in polycystic ovarian syndrome. AB - To assess the morphological findings based on transvaginal ultrasound, the ovarian volume and the number and size of small follicles were studied in 47 patients with polycystic ovarian syndrome (PCOS) diagnosed clinically. Thirty normal volunteers served as controls. The mean ovarian volume (10.3 ml) and number of follicles (10.6) in patients with PCOS were significantly higher than those of controls. An ovarian volume > 6.2 ml and follicles > 10 with a diameter of 2-8 mm were the most prominent features in the ovaries of patients with PCOS and 94% of 47 patients with PCOS had at least one of these ultrasonic findings. However, marked asymmetry of the two ovaries was seen in about 50% of patients with PCOS and a considerable overlap existed between controls and patients with PCOS in the ovarian volume and in the number of follicles. Three (6%) patients with normal ovarian volume and normal number of follicles were observed. Therefore, it is difficult to clearly distinguish a patient with PCOS from a normal woman only by transvaginal ultrasonic criteria using the ovarian volume and/or the number of follicles, although these criteria could be clinically useful for the screening of PCOS. PMID- 7789919 TI - Danazol suspension injected into the uterine cervix of patients with adenomyosis and myoma. Preliminary study. AB - We investigated the effect of local injections of danazol suspension (DZS) into the uterine cervix. In the cervix, danazol (DZ) reached high concentrations 1 and 4-6 h after injection; then it decreased. In the endometrium, the DZ level reached a peak 1 h after injection, and then declined. On the other hand, the DZ concentration tended to increase with time after injection in ovarian tissue and it remained at a relatively constant level for more than 2 days. During treatment with DZS, various subjective symptoms and clinical findings gradually improved from the 4th week after the start of injection onward. Moreover, an improvement of subjective symptoms was observed in all the patients by the 24th week. PMID- 7789920 TI - Management of supraventricular tachycardia during hexoprenaline therapy for preterm labour: benefit of cardioselective beta blockade? AB - A 29-year-old woman presented with preterm labour at 32 weeks of gestation. Tocolytic treatment was started with intravenous hexoprenaline. Twenty-four hours after initiation of treatment, the patient developed supraventricular tachycardia, resistant to digoxin and verapamil. Medical treatment with metoprolol finally restored sinus rhythm. We observed no adverse effects on the fetal heart rate nor on the umbilical cord blood flow. PMID- 7789921 TI - False diagnosis of distal tubal occlusion in case of tubal diverticula. AB - A 28-year-old infertile patient with a diagnosis of bilateral distal tubal occlusion made at hysterosalpingography and laparoscopy was found at a second laparoscopy to have bilateral single diverticula in patient tubes. The patient conceived an intrauterine pregnancy 5 months after discharge. This report casts doubt on the suggested association between tubal diverticula and infertility. PMID- 7789923 TI - [A retrospective evaluation of the treatment of skeletal Class-II with removable appliances]. AB - Pre- and post-treatment lateral radiographs of 120 former patients with skeletal class II, who had been treated with either an Andresen/Haupl type activator or bite jumping plates, were selected for this study. The evaluation results showed that bite jumping plates had a significant inhibition on the forward downward growth and the anterior rotation of the maxilla. The increase of the SNB-angle was significantly higher and there was also more posterior rotation of the maxilla in those patients, who had been treated with an activator. A two-way analysis of variance was carried out and it was possible to show that the independent treatment factors explained only 1/5 to 1/3 of the overall variance of the sample. The differences among the patients seem to depend more on individual growth patterns than just on the type of removable appliance. PMID- 7789922 TI - [Skeletal and dental changes during the use of the bite-jumping plate. A cephalometric comparison with an untreated Class-II group]. AB - In this study 95 patients with a malocclusion type Angle class II were treated with a bite jumping appliance and the results achieved were compared with untreated class II patients. A clear improvement in the skeletal and dental relationships was observed. Significant changes were achieved yearly in the following: 1. the angle SNA was reduced (0.82 degrees), 2. the angle SNB was increased (0.57 degrees), 3. the angle ANB was reduced (1.39 degrees). All 3 of these variables are significant. Other skeletal variables, most notably the incline of the maxilla to the line NS, were not influenced nor was the relation of posterior facial height to anterior facial height. The mandibular incisors did not exhibit increased protrusion relative to the mandibular plane. Only the angle of the mandibular incisor to NB was changed by the total protrusion of the mandible. The maxillary incisors in these cases manifested obvious lingual tipping. For this reason the orthodontist must weigh carefully on an individual patient basis, whether the use of adjunctive torque springs is required and necessary. PMID- 7789925 TI - [A critical evaluation of the functional treatment of mandibular neck fractures in children. The results of a spiral computed tomographic follow-up]. AB - In this retrospective follow-up study after 6 months of treatment with functional appliance therapy of 12 children who had suffered condylar fractures, spiral CT was employed for the radiological examination with 2D and 3D reconstructions. Although all patients exhibited restoration of normal function, only 4 showed favorable remodeling. The other patients had developed 5 hypoplastic, 5 moderate and 5 severe deformed condyles. Seven condylar fragments were resorbed; 2 were uprighted; 4 had developed bony spurs and 3 neoarthrosis. The results revealed a fracture dependent remodeling. The authors discuss the etiology of the functional stimulated new bone formation of the condylar process. Excessive bone apposition as a reaction to the anterior shift of the mandible seems to play an important role during the overgrowth of the head of the condyle. PMID- 7789924 TI - [Problems and risks in the movement of the mandibular anterior teeth]. AB - The key role of the lower anterior incisors as well as the complicated anatomical relationship of this area play a significant part in orthodontic treatment planning. Three fundamental points of view are selected here for discussion: 1. the variability and clinical relevance of the initial periodontal findings, 2. the importance of the symphysis to sagittal and vertical tooth movement, and, 3. the specific problem associated with periodontal bone loss. The few clinical and experimental studies found in the literature indicate that every anterior tooth movement has to be oriented according to the structure and facio-lingual width of the alveolar bone and that movement should progress in a controlled fashion. Rapid tipping tooth movements are to be avoided so as to minimize the risk of bone dehiscences and root resorption. Orthodontic tooth movement should be avoided when the initial findings show a narrow symphysis or questionable labiolingual bone coverage. Pre-orthodontic thin gingiva and alveolar mucosa can be an indication for a mucosal graft aimed at preventing subsequent bone and gingival dehiscences. In the future, systematic 3-D CT analysis of pre orthodontic and post-orthodontic findings will contribute to a better estimation of the case specific potential of compensatory bone apposition. PMID- 7789926 TI - [Cervical headgear with angled outer arms. A biomechanically comprehensible system?]. AB - When applying the angulated face bow, it doesn't seem possible to avoid vertical and transversal forces which occur in addition to the distalization force as moments. By varying the length and angulation of the outer bow, it is possible to influence the force components and the moments in the sagittal plane. In the clinical analysis of the force system it is assumed that the face bow is an ideal rigid system. Only under this presupposition is the assumption valid, that the product of the force and the perpendicular distance to the molar tube is responsible for the size of the moment. Under this assumption, however, all forces and moments created by the deflection of the headgear are not taken into consideration. An experimental analysis of the forces and turning moments which occur indicates that this simplifying geometric point of view does not always correspond to reality. It was evident, e.g., that there is no linear correlation between the force and moment in mesio-distal direction due to the deflection of the outer bow. This effect becomes the more obvious the longer the outer bow of the headgear is. PMID- 7789927 TI - [The development of a resorbable implant system for orthodontic anchorage. The BIOS implant system. Bioresorbable implant anchor for orthodontic systems]. AB - The use of endosseous implants as temporary orthodontic anchoring elements has proven itself to be efficacious in many clinical applications. If, however, an implant is inserted into the jaw solely to correct a malocclusion without being used subsequently for prosthetic purposes, secondary surgery is required to remove the anchoring implant. The development of an orthodontic implant anchor system consisting of an implant made of biodegradable polylactide with a metal abutment may offer a solution to this problem. On the basis of its good mechanical properties, the BIOS implant system (bioresorbable implant anchor for orthodontics system) presented here is designed to assume orthodontic anchoring functions as long as necessary and then be resorbed by hydrolysis without foreign body reactions. Shear strength and maximum vertical strength were measured in biomechanical in vitro tests in which BIOS fixtures can be loaded with horizontal shear forces of 50 N with a mean deflection of 0.26 mm and mean vertical pull-off forces of 155 N. In a clinical case report the application of the BIOS implant system during orthodontic tooth movement is here illustrated. In vitro and in vivo results obtained to date suggest that the BIOS implant system can be used as an orthodontic anchoring system up to the time of degradation. PMID- 7789929 TI - [Anti-HIV drugs work rapidly or not at all. Virus dynamics--therapeutic consequences]. PMID- 7789928 TI - [Report on the 7th Interdisciplinary Symposium. The Interdisciplinary Working Group on Cheilo-gnatho-uranoschisis]. PMID- 7789930 TI - [Genetic techniques in food production--also a medical problem]. PMID- 7789931 TI - [Polymyalgia rheumatica in patients of a rheumatologic specialty practice. Clinical signs and etiological events]. AB - Manifestations of polymyalgia rheumatica in 100 ambulatory patients of an internistic, rheumatological specialist's practice were investigated. In this group of patients, both the clinical course of the disease and its prognosis were found to be more benign than is commonly reported in the literature. Thus, for example, temporal arteritis was found in only three of the one hundred patients. Not all of the patients were found to have the markedly elevated ESR normally considered to be typical. For this reason, to establish inflammatory activity, in addition to ESR, C-reactive protein (CRP) should also be determined in order to ensure that atypical forms with less marked signs of inflammation are not overlooked. Thirty of the 100 patients reported possible triggering life events. PMID- 7789932 TI - [Psychiatric consultation before liver transplantation]. AB - BASIC REMARKS: Since the long-term results of transplantations are highly dependent on patient compliance, prior to the decision to undertake such an operation, the psychiatrist is often asked whether there are any conditions presenting that would militate against the necessary cooperation. METHOD: Between 1992 and 1993, 35 patients were sent for psychiatric counselling prior to liver transplantation, and were evaluated using a standardised questionnaire. 23 of the 35 patients were submitted to psychological testing. RESULTS: in 23 cases, a psychiatric diagnosis was established in accordance with the ICD-10 criteria. The largest group was formed by the addictive diseases in this study, in particular alcohol dependence. Eight patients proved to have organ-related mental disturbances, other diagnoses such as depressive disorders or personality disorders were less common. In four cases, the psychiatrist was unable to recommend the liver transplantation. In such cases as these, the tasks of the psychiatrist is not restricted simply to a diagnostic assessment, but must also include a therapeutic approach intended to enable the patient to cope with the coming stresses and requirements. PMID- 7789933 TI - [Acute poisoning. 4: Antidote therapy]. PMID- 7789934 TI - [Externalizing and overcoming psychological crises with role playing. Psychotherapy, 8: Psychodrama therapy]. PMID- 7789935 TI - [Determination of C-reactive protein--an alternative to blood sedimentation rate? Quantitative and semi-quantitative CRP diagnosis in the course of bacterial infections]. PMID- 7789936 TI - [What is the status of vasoactive drugs? Early stages of arterial occlusive disease in general practice--positive series list, 3]. PMID- 7789937 TI - SARP: a value-based approach to hospice admissions triage. AB - As hospices become established and case referrals increase, many programs are faced with the necessity of instituting waiting lists. Prioritizing cases for order of admission requires a triage method that is rational, fair, and consistent. This article describes the SARP method of hospice admissions triage, which evaluates prospective cases according to seniority, acuity, risk, and political significance. SARP's essential features, operative assumptions, advantages, and limitations are discussed, as well as the core hospice values which underlie its use. The article concludes with a call for trial and evaluation of SARP in other hospice settings. PMID- 7789938 TI - The McCanse Readiness for Death Instrument (MRDI): a reliable and valid measure for hospice care. AB - The purpose of this study was to establish whether or not readiness for death, as an indicator of healthy dying, is a measurable concept. Review of relevant literature revealed consensus regarding the universality of a human need for healthy dying. A theory of healthy dying was derived from the Rogerian paradigm. The McCanse Readiness for Death Instrument (MRDI) was constructed, which included indicators of physiological, psychological, sociological, and spiritual aspects of "healthy" field pattern as death is developmentally approached. The MRDI was a 26-item structured interview questionnaire which generated interval-ratio data through a visual analog scale. A pretest was conducted with a sample of 9 volunteer patients drawn from a small suburban outpatient hospice. The MRDI was concurrently administered to dying individuals, their primary caregivers, and their primary hospice nurses. Correlations between dying individuals' scores and their primary caregivers' estimates of patient death readiness as well as between patients and their primary hospice nurses were very encouraging. Cronbach's coefficient alpha for internal consistency reliability was .59. Content validity was supported by consensus of an expert panel of practicing hospice nurses. Construct validity was demonstrated through legitimate placement of the concept, healthy death readiness, within the theoretical web which supported it. The MRDI was then administered to a sample of 31 terminally-ill individuals, their primary caregivers, and their primary hospice nurses drawn from larger, urban hospice populations in three geographic areas of the United States. The MRDI was also administered to a contrast group of 39 cardiac-impaired individuals who were not terminally-ill. Overall internal consistency of the MRDI was found to be quite favorable (alpha = .76). Debilitating illness and actual mortality in the study sample precluded and/or confounded estimates of test-retest reliability. Convergent validity of the MRDI was indicated by significant correlations between patients' scores and primary caregivers' estimates (r = .35, p < .05) and between patients' scores and primary hospice nurses' estimates (r = .53, p < .01). Discriminant validity of the MRDI was demonstrated by a significant mean difference between the group of terminally-ill patients and the group of non terminal, cardiac-impaired patients (t = 1.76, p < .01). PMID- 7789939 TI - A family caregiving model for hospice nursing. AB - The literature reveals only superficial description of the clinical judgment needed to practice hospice nursing. Practice wisdom remains vague and taken for granted. To improve documentation of the nature of hospice nursing practice, 32 expert hospice nurses were asked to tell stories of memorable practice experiences. Those narratives were interpreted using qualitative methodology to identify 10 hospice nursing practice competencies and a visual model of practice. This model can be used to articulate hospice nursing practice to students, fellow professionals, and those making decisions about health care in the future. PMID- 7789940 TI - The relationship between hospice length of stay and caregiver adjustment. AB - This study investigated the hypothesis that the greater the predeath length of stay in hospice the better would be the primary caregivers' bereavement adjustment 6 months post death. One hundred sixty caregivers from a 30% pool of hospice survivors who voluntarily returned 6-month, follow-up questionnaires were studied. Five length of stay groups were compared. There were no statistically significant differences in bereavement adjustment between caregivers with varying predeath lengths of stay. It was concluded that bereavement resolution is a complex process, and that cumulative medical illness burden, impairment of ADLs, and caregiver burden need to be considered. PMID- 7789941 TI - Empathic nurse-patient relationships in hospice nursing. AB - This naturalistic study explored the development of empathic nurse-patient relationships between 10 terminally ill adult hospice patients and their hospice nurses. The data were collected and analyzed from the hospice patient's perspective. Content analysis and the constant comparative method were used to analyze the transcripts of the audio taped interviews. The findings suggest that the development of empathic relationships between hospice nurses and patients was a process that occurred most often over time and involved a reciprocal sharing. Specific patient needs, nurses' functions, attributes, and the patient's reciprocity contributed to the development of the empathic relationship. PMID- 7789942 TI - Analysis of variables that impact psychological adaptation in home hospice patients. AB - In their efforts to understand the psychological impact of life-threatening illness upon individuals, researchers, for the most part, have focused on the distress associated with dying rather than the influences that promote adaptation. Early studies report relationships between the mental state of the dying and variables of age, religiosity, family relationships, and physical discomfort. This article analyzes and compares the influences of social support, pain, and age, which were confirmed in a causal model study, as direct predictors of an outcome of psychological adaptation. The data from a sample of 97 home hospice subjects is compared with other healthy, recovering ill, advanced ill, and psychiatric populations. PMID- 7789943 TI - A descriptive study of the management of pain and pain-related side effects in a cancer center and a hospice. AB - The purpose of this study was to describe the pain and pain-related symptoms experienced by persons receiving treatment in a cancer center or a hospice and to describe the nurses' responses to these problems. The sample consisted of 25 hospice and 19 cancer center patients who were being treated for pain. Pain was assessed three times in a 24-hour period using a visual analogue scale (VAS). Constipation was assessed using the Constipation Assessment Scale. Sedation was assessed on a 0 (fully alert) to 4 (comatose) scale. The nurses' documentation was assessed using the Chart Audit for Pain. Results showed that patients in the cancer center and hospice continued to experience pain (VAS M = 38.6 and 29.7 respectively) in spite of their pain management regimens. The cancer center patients were given an average of 38% of the maximum ordered dose of analgesic while the hospice patients self-administered 93% of the ordered dose. The cancer center nurses documented the efficacy of the analgesics in only 26% of cases while hospice nurses recorded this information in 96% of the charts. Sedation was not found to be a problem. Constipation was reported by 100% of cancer center patients and 84% of hospice patients but was rarely documented by nurses in either setting. It appears that nurses need to do more thorough assessment of patient symptoms and more consistent follow-up evaluation and documentation. PMID- 7789946 TI - Assignment of the gene responsible for cystinuria (rBAT) and of markers D2S119 and D2S177 to 2p16 by fluorescence in situ hybridization. AB - We have established rBAT (named as SLC3A1 in the Genome Data Base) as a gene responsible for cystinuria, a heritable disorder of amino acid transport. The cystinuria locus has been mapped by linkage between microsatellite markers D2S119 and D2S177. Fluorescence in situ hybridization (FISH) either with Alu-polymerase chain-reaction (PCR)-amplified sequences of a yeast artificial chromosome (YAC) containing the rBAT gene or with rBAT-specific PCR-amplified genomic fragments, and chromosome G-banding have cytogenetically mapped rBAT to 2p16.3. In order to correlate the physical and genetic information on cystinuria, we have performed FISH with combinations of Alu-PCR-amplified sequences from YACs containing rBAT or the D2S119 and D2S177 loci. In all cases, a fused signal is obtained that demonstrates their close physical location; this allows the assignment of rBAT, cystinuria and their linked markers, D2S119 and D2S177, to 2p16. PMID- 7789945 TI - Molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency in three Taiwan aboriginal tribes. AB - We have investigated glucose-6-phosphate dehydrogenase (G6PD) deficiency in 220 unrelated aboriginal male subjects who belong to three different tribes (Saisiat, Ami, and Yami) in Taiwan. Our results show that the G6PD deficiency rates for Saisiat, Ami, and Yami people are 9.0% (6/67), 6.1% (6/99), and 0% (0/54), respectively. Among these deficiency cases, 4 of 6 (66.7%) Saisiat subjects have the 493 A-->G mutation and one carries the 1376 G-->T mutation, whereas, in Ami subjects, we found that four of six (66.7%) affected males have the 592 C-->T mutation and one carries the 493 A-->G mutation. These results contrast with our previous findings for Taiwan Chinese, in whom the 1376 G-->T mutation is the major mutant allele and accounts for 52.3% of the deficiency cases. This is the first report of G6PD deficiency characterized at the DNA level in Taiwan aboriginal populations. PMID- 7789947 TI - Coverage of chromosome 6 by chromosome microdissection: generation of 14 subregion-specific probes. AB - Human chromosome 6 has been subdivided by chromosome microdissection into 14 unique regions. Following microdissection, polymerase chain reaction (PCR) amplification of dissected DNA was performed using a universal primer to generate subregion-specific probes that provided complete coverage of chromosome 6. All 16 microdissections have been regionally assigned along chromosome 6 by fluorescence in situ hybridization (FISH) using biotin-labeled dissected DNA hybridized to G banded normal metaphase chromosomes. These probes can be used as region-specific paints to generate unique "bar codes" and for analysis of chromosome alterations involving chromosome 6 that are unidentifiable by conventional banding analysis. PMID- 7789948 TI - Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms. AB - Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin-1 beta-converting enzyme. Overexpression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation. The potential tumour suppressor function of NEDD2 is discussed. PMID- 7789949 TI - Genetic heterogeneity of polycystic kidney disease in Bulgaria. AB - Linkage analysis was performed on 22 Bulgarian families with polycystic kidney disease (PKD) ascertained through the hemodialysis centers of two medical schools. A total of 128 affected and 59 unaffected individuals, and 54 spouses have been investigated using eight polymorphic markers linked to PKD1 and nine markers to PKD2. The results demonstrate locus heterogeneity with 0.67 as the maximum likelihood value of alpha, i.e., the proportion of families linked to PKD1. In five families, the results suggest linkage to PKD2 and observed recombinants place the gene between loci D4S1544 and D4S1542. In one family, two double recombinants for closely linked markers on chromosome 16 and on chromosome 4 give evidence for the lack of linkage to either PKD1 or PKD2, thus suggesting the involvement of a third locus. Analysis of clinical data in the PKD1 group versus the unlinked group shows no significant differences in the severity of the disease. PMID- 7789950 TI - Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms' tumour from a BWS patient. AB - A patient with Beckwith-Wiedemann syndrome (BWS) presented with Wilms' tumour. Examination of the nephrectomy specimen showed, in addition to the tumour, the presence of nephrogenic rests. Nephrogenic rests are thought to be precursor lesions from which a Wilms' tumour may develop. A molecular analysis examining the loss of constitutional heterozygosity (LOCH), initially for chromosome 11, was performed on peripheral blood, the normal kidney, nephrogenic rest and tumour material. The study was extended to include markers from all 23 chromosomes. At each informative, locus, LOCH of the maternal allele was shown in the nephrogenic rest and tumour material. In addition, the normal kidney displayed allele imbalance. It would appear from these results that either extensive LOCH across the genome was an early genetic event in the development of malignancy in this patient or that the tumour and rest developed from cells containing no maternal chromosomes. The apparent LOCH seen in the normal kidney sample implies that full reduction to homozygosity is consistent with a histologically normal appearance. Putative mechanisms to explain this phenomenon are discussed. PMID- 7789951 TI - Intricate combinatorial patterns of exon splicing generate multiple Rh-related isoforms in human erythroid cells. AB - The Rhesus (Rh) blood group system shows complex polymorphisms in the human. Some of the heterogeneity may be generated by alternative RNA splicing. For a systematic analysis of Rh-related mRNA isoforms expressed in reticulocytes, we isolated mRNA, which was then reverse transcribed and amplified by the polymerase chain reaction (PCR) to give Rh-related cDNAs of two segments of 704 bp and 975 bp. The PCR amplification of the 5'-region yielded a single PCR product, whereas a complex electrophoretic pattern of PCR bands was derived from the 3'-region. A highly reproducible ladder of multiple additional bands migrated below the PCR products corresponding to the full-size cDNAs for RhPI and RhPII and encoding two different Rh polypeptides. Eleven and five truncated isoforms of the RhPI and RhPII cDNAs, respectively, were identified in the PCR products. These isoforms appear to be generated by combinatorial splicing of six RhPI and three RhPII exons. Our results suggest that the Rh-related polypeptides consist of a mixture of RhPI and RhPII polypeptide isoforms differing at the C terminus. Multiple RNA splicing pathways are thus operative in the two Rh-related genes even within a single cell lineage of human erythroid cells. PMID- 7789952 TI - Recurrence of osteogenesis imperfecta because of paternal mosaicism: Gly862-->Ser substitution in a type I collagen gene (COL1A1). AB - We determined that two siblings with type III osteogenesis imperfecta (OI) had the same single base substitution that converted the codon for glycine (Gly) 862 to a codon for serine (Ser) in exon 44 of the alpha 1 chain of the type I (alpha 1(I)) collagen gene (COL1A1). The mutation was also detected in various paternal tissues; the mutant allele accounted for approximately 11% of the COL1A1 alleles in blood, 24% of those in fibroblasts, and 43% of those in sperm determined by allele-specific colony hybridization using amplified genomic sequences. These findings demonstrate that germ-line mosaicism in the phenotypically normal father is responsible for the recurrence. There is a cluster of serine substitutions for Gly (Gly832, Gly844 and Gly901) which is associated with nonlethal phenotypes and which is located between two lethal clusters. In the cases studied here, a Gly862 ->Ser mutation was identified that is located inside the nonlethal cluster. PMID- 7789944 TI - Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. AB - Although clinical features in Turner syndrome have been well defined, underlying genetic factors have not been clarified. To deduce the factors leading to the development of clinical features, we took the following four steps: (1) assessment of clinical features in classic 45,X Turner syndrome; (2) review of clinical features in various female sex chromosome aberrations (karyotype phenotype correlations); (3) assessment of factors that could lead to Turner features; and (4) correlation of the clinical features with the effects of specific factors. The results indicate that the clinical features in 45,X and in other female sex chromosome aberrations may primarily be determined by: (1) degree of global non-specific developmental defects caused by quantitative alteration of a euchromatic or non-inactivated region; (2) dosage effect of a pseudoautosomal growth gene(s), a Y-specific growth gene(s), and an Xp-Yp homologous lymphogenic gene(s); and (3) degree of chromosome pairing failure in meiocytes that are destined to develop as oocytes in the absence of SRY. 1991; Grumbach and Conte 1992). However, the pertinent factors have not been determined to date. The method to clarify the factors responsible for the development of the Turner phenotype can be broken down into the following steps: (1) assessment of clinical features in classic 45,X Turner syndrome; (2) review of clinical features in various female sex chromosome aberrations (karyotype-phenotype correlations); (3) assessment of factors that could lead to Turner features; and (4) correlation of the clinical features with the effects of specific factors. If the clinical features in 45,X and in other female sex chromosome aberrations are explained by the effects of specific factors, it can be said that such factors contribute to the development of Turner features. In this paper, we take each of the above steps, and propose the principal factors involved in the development of clinical features in Turner syndrome. PMID- 7789954 TI - Linkage mapping of serotonin transporter protein gene SLC6A4 on chromosome 17. AB - Abnormalities in monoamine metabolism, including serotonin metabolism, have been implicated in the pathophysiology of affective disorders, schizophrenia, suicide, and other psychiatric disorders. Serotonin transporter protein (SERT) allows neurons to retrieve serotonin that has been released into a synapse. SERT is a site of action for several drugs with CNS effects, including both therapeutic agents (e.g., antidepressants) and drugs of abuse (e.g., cocaine). This gene had previously been physically mapped to chromosome 17. We used a PCR product corresponding to the 3' untranslated region of the gene as a probe to identify restriction fragment length polymorphism (RFLP), which we then used to establish that the SLC6A4, genetic locus for SERT, is near 17q12 and probably flanked by D17S58 and D17S73 (a location consistent with observed crossovers). These data should be useful for linkage studies of neuropsychiatric disorders. PMID- 7789953 TI - Screening for known mutations in the LDL receptor gene causing familial hypercholesterolemia. AB - Familial hypercholesterolemia (FH) is caused by defective low density lipoprotein (LDL) receptors and is characterized by hypercholesterolemia and premature coronary heart disease. Two strategies can be used to identify the mutation in the LDL receptor gene underlying FH. One strategy is to search for novel mutations by DNA sequencing with or without prior mutation screening. The other strategy is to screen for known mutations. In this study we employed the latter strategy to screen 75 unrelated, Norwegian FH subjects for 38 known mutations. Three of the 38 mutations were detected in our group of FH subjects. Two subjects had FH-Padova, one had FH-Cincinnati-2 and one had FH-Gujerat. When additional unrelated FH heterozygotes were screened for the three mutations, the gene frequencies were 1.3%, 1.0% and 3.0%, respectively. In addition to identifying known mutations we also detected a novel stop codon in codon 541 (S541X). We conclude that screening for known mutations in the LDL receptor gene should be used as a complementary strategy to screening for novel mutations in order to understand the molecular genetics of FH. PMID- 7789955 TI - Identification of a candidate missense mutation in a family with von Willebrand disease type IIC. AB - A screening project to identify candidate molecular defects causing von Willebrand disease type IIC (VWD IIC) in a German family was carried out using polymerase chain reaction (PCR) amplification of all 52 exons of the von Willebrand factor (VWF) gene, subsequent electrophoresis of single and double stranded DNA and direct sequencing of PCR products with aberrant electrophoretic patterns. Only one candidate mutation, G550R, caused by a G-->A transition, was detected in exon 14 of the pro-VWF gene sequence. This mutation was not found on 200 chromosomes of normal individuals. The propositus was homozygous for the mutation and for an extended intragenic haplotype, composed of eight polymorphic markers. Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance for VWD type IIC. The mutation could influence one of the presumed active centers for the suspected multimerizing enzymatic activity of pro VWF localized in the D1 and D2 domain, which corresponds to exon 5 and exon 14 of the VWF gene. PMID- 7789957 TI - High incidence of cystic fibrosis on the Faroe Islands: a molecular and genealogical study. AB - We have studied the genetics of cystic fibrosis (CF) in The Faroe Islands. Based on the number of affected children born during the period 1954-1993, the incidence of CF at birth is 1:1775, which is more than twice the incidence in the rest of Denmark. We have tested all known CF patients and/or their parents for the presence of delta F508 and found it to be the only CF mutation in this population. Based on testing 881 unrelated control individuals, the carrier frequency was estimated to be 1:24, given a calculated incidence of 1:2300. Genealogical studies enabled us to trace several of the families over seven generations. Haplotype investigations within the families suggest that delta F508 was introduced by two founders, probably from the Celtic population in Brittany, Ireland, Wales or the North West of Scotland. PMID- 7789956 TI - Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three generation family. AB - Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare but well-defined clinical entity that is usually inherited as an autosomal dominant trait. A limited number of patients carry a deletion in chromosome 20p, with 20p11.23 p12.2 as the area of minimal overlap. Recently, a family has been identified in which a balanced translocation with a breakpoint in 20p12 co-segregates with the AGS phenotype. Here, we report a three-generation family with AGS and in which the affected members have a normal karyotype. Linkage analysis was performed with markers from the 20p candidate region. A lod score of Z = 2.96 was obtained with D20S27 at no recombination. Combining D20S27 and D20S61 to a single highly informative locus resulted in a maximum lod score of Z = +3.56 at theta = 0.0. Haplotype analysis positioned AGS between D20S59 and D20S65, markers that define an interval of about 40 cM. Allelic loss was not observed for the tested markers and no abnormalities in the PAX1 candidate gene were detected. These findings demonstrate that the locus on chromosome 20p could be responsible for AGS in cytogenetically normal patients and argues for a general role of this locus in the aetiology of AGS. PMID- 7789958 TI - A novel splicing mutation in propionic acidemia associated with a tetranucleotide direct repeat in the PCCB gene. AB - Propionic acidemia is an inborn error of organic acid metabolism caused by a deficiency of propionyl Coenzyme A (CoA) carboxylase. cDNAs sequenced from a beta subunit deficient Japanese patient (no. 187) showed an in-frame 57-bp deletion in one allele. Genomic DNA analysis revealed a four-nucleotide deletion of bases 3 to 6 in the 3' intron adjacent to the deleted exon, which disrupted the consensus 5' splice signal and caused exon skipping. This deletion removed one-half of a tetranucleotide direct repeat at the splice junction and presumably resulted from slipped mispairing. PMID- 7789959 TI - Redefinition of the coding sequence of the MXI1 gene and identification of a polymorphic repeat in the 3' non-coding region that allows the detection of loss of heterozygosity of chromosome 10q25 in glioblastomas. AB - The MXI1 gene encodes a protein interacting with Max, a regulatory factor of the Myc oncogene, and is located on chromosome 10q25, a region showing frequent loss of heterozygosity in malignant gliomas. We have reassessed the coding sequence of MXI1 and found that, at the 3' end, the open reading frame is 28 codons shorter than previously described. We have also found an AAAAC polymorphic repeat (two alleles, 45% heterozygosity) in the 3' non-coding region of the gene. Six anaplastic astrocytomas and nine glioblastomas, the most malignant form of glioma, were informative for this polymorphism. Loss of heterozygosity was demonstrated in all glioblastomas, but not in the remaining tumors. PMID- 7789960 TI - Highly polymorphic dinucleotide repeat at the NF2 gene. AB - A highly polymorphic CA repeat was identified in a cosmid containing the 5' end of the NF2 tumour suppressor gene. This marker has proved useful in presymptomatic diagnosis in affected families. PMID- 7789961 TI - An intragenic deletion in the human PTPN6 gene affects transcriptional activity. AB - An intragenic deletion in the human PTPN6 gene is described. The PTPN6 gene maps to chromosome 12p12-13 and is shown to possess two alternative first exons. A 1.7 kb deletion occurring in the intron between the two alternatively used first exons is the result of an illegitimate recombination between two Alu-type repeats. The deletion increases the transcriptional activity of the distal promotor. PMID- 7789962 TI - Frequent sequence variant in the human tyrosine hydroxylase gene. AB - A polymorphism of human tyrosine hydroxylase changing the amino acid 81Val to 81Met is located in exon 2 of the human tyrosine hydroxylase gene. PMID- 7789964 TI - Highly polymorphic sequence at D21S1448 mapping close to D21S55, within the Down syndrome critical region. AB - We have isolated a highly polymorphic sequence from the Down syndrome critical region on human chromosome 21. This is a particularly useful marker because it lies adjacent to the locus D21S55, which is most closely associated with the major defects on Down syndrome. Other than this marker, few other variable sequences are known in this region (including other restriction fragment length polymorphisms or CA repeats) and therefore D21S1448 will be extremely helpful not only for people studying the inheritance of portions of chromosome 21 with respect to Down syndrome, but also for those carrying out linkage analysis of the chromosome. PMID- 7789963 TI - Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients: absence of the common Jewish 84GG and 1226G mutations. AB - The prevalence of seven different mutations (84GG, IVS2 + 1, 754A, 1226G, 1342C, 1448C, and 1504T) was investigated in 32 unrelated Japanese Gaucher patients of which 20 were type I, 6 were type II, and 6 were type III). These mutations constitute 95% of the mutations observed in Jewish patients with Gaucher disease and 75% of the mutations in non-Jews (European). The most frequent mutation, 1448C (L444P), accounted for 26 alleles (40.6%); the second most prevalent mutation was 754A (F213I), accounting for 7 alleles (10.9%); 27 alleles (42.2%) were unidentified. To data, neither the 1226G (N370S) nor 84GG mutations have been identified in the Japanese population though these alleles account for approximately 70% and 10% of mutations in the Jewish population. These data suggest that mutant alleles identified from the Japanese population are distinct from those observed in Jewish and non-Jewish (European) patients with Gaucher disease. PMID- 7789965 TI - A trinucleotide repeat combination polymorphism in the cardiac alpha myosin heavy chain (MYH6) gene. AB - A polymorphic trinucleotide repeat combination (GAA)m(GAG)n has been demonstrated in the cardiac alpha myosin heavy chain gene (MYH6), which is located on chromosome 14q, and which is sometimes involved in familial hypertrophic cardiomyopathy. Based on length, at least seventeen alleles varying from 31 to 50 repeats have been detected in a sample of 55 unrelated individuals. PMID- 7789966 TI - High yield of restriction fragment length polymorphisms in two-dimensional separations of human genomic DNA. AB - We have investigated the extent to which restriction fragment length polymorphism can be detected by two-dimensional electrophoresis of end-labeled genomic restriction fragments. Genomic DNA was digested with NotI and EcoRV and labeled at the NotI recognition site before first-dimension electrophoresis in disk gels. DNA in the disk gels was further digested in situ with HinfI prior to second dimension electrophoresis, yielding patterns in which approximately 2000 end labeled fragments were simultaneously visualized. On the basis of studies of 6 mother/father/child trios, a group of 184 fragments was organized into 85 polymorphic systems in which all allelic fragments were detectable in the 2-D patterns. Another 206 fragments varied as to their presence among individuals, but their relatedness to other fragments was not established. Our data indicate that a large number of DNA polymorphisms can be simultaneously scored in 2-D separations of genomic DNA fragments. PMID- 7789968 TI - Refined genetic mapping of a gene for familial juvenile nephronophthisis (NPH1) and physical mapping of linked markers. APN Study Group. AB - We have recently assigned a gene for familial juvenile nephronophthisis (NPH1) to chromosome 2q between microsatellite markers at loci D2S135 and D2S110. Here we have extended and refined our previous linkage analysis by studying five additional NPH families and by testing five additional markers. By haplotype analysis in a large family yielding proof of linkage, D2S135 and D2S283 were defined with certainty as flanking the NPH1 critical region within a 14-cM interval. These data now allow cytogenetic assignment of the NPH1 critical region to 2q11.1-q21.1. Furthermore, haplotype analysis in 12 small families helped to define as flanking markers D2S293 and D2S363, which span an 8-cM interval. Multipoint linkage analysis by the location score method resulted in a maximum multipoint lod score of 10.30. The Zmax-1 support interval spans 6.9 cM and is flanked by marker loci D2S293 and D2S363. Since IL1A maps to this region and has been cytogenetically mapped to 2q13 in the literature, NPH1 can be assigned more closely to 2q13 or adjacent bands. Contigs of CEPH mega-YAC clones in the region were established by screening the clones with microsatellite markers, adding marker IL1A to the physical map as a novel assignment. We conclude that the NPH1 gene most probably localizes to an interval of 6.9 cM between marker loci D2S293 and D2S363 in the vicinity of 2q13. This contig mapping provides the basis for cloning of this interval and for isolation of the NPH1 gene. PMID- 7789967 TI - POM-ZP3, a bipartite transcript derived from human ZP3 and a POM121 homologue. AB - Human POM-ZP3 is a novel bipartite RNA transcript that is derived from a gene homologous to rat POM121 (a nuclear pore membrane protein) and ZP3 (a sperm receptor ligand in the zona pellucida). The 5' region is 77% identical to the 5' end of the coding region of rat POM121 and appears to represent a partial duplication of a gene encoding a human homologue of this rodent gene. The 3' end of the POM-ZP3 transcript is 99% identical to ZP3 and appears to have arisen from a duplication of the last four exons (exons 5-8) of ZP3. Using Northern blots and RT-PCR, POM-ZP3 transcripts were detected in human ovaries, testes, spleen, thymus, lymphocytes, prostate, and intestines. The longest open reading frame encodes a conceptual protein of 210 amino acids, the first 76 of which are 83% identical to residues 241-315 of rat POM121. The next 125 amino acids are 98% identical to residues 239-363 of the 424-amino-acid human ZP3 protein. By fluorescence in situ hybridization, genomic fragments of ZP3 and a human homologue of POM121 were localized to chromosome 7q11.23. Taken together, these data suggest that partial duplications of human ZP3 and a POM121-like gene have resulted in a fusion transcript, POM-ZP3, that is expressed in multiple human tissues. PMID- 7789969 TI - Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1. AB - Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a major nuclear protein and one of the major components of the hnRNP core complex in mammalian cells. We first determined the complete sequence of the human gene for hnRNP protein A2 (HNRPA2B1). The human HNRPA2B1 gene exists in a single copy over 9 kb in length. The gene was split into 12 exons, including a 36-nucleotide mini-exon, which was specific to the hnRNP protein B1, providing genetic evidence that the B1 mRNA was generated from the primary HNRPA2B1 transcript by alternative splicing. The 5' region of HNRPA2B1 was GC-rich and contained several DNA motifs for the binding of several transcription factors, which included 2 CCAAT boxes and no TATA sequences. The 5' ends of the mRNA were mapped to multiple positions. These structural features are characteristic of promoter regions of housekeeping genes. Northern blot and RT-PCR analyses of the HNRPA2B1 transcripts revealed levels of B1 mRNA from 2 to 5% of total A2/B1 transcripts and showed that both A2 and B1 mRNAs were transcribed in all human cell lines and mouse tissues studied. The structural and evolutionary characteristics of the A2 and A1 proteins as they relate to each other are discussed. PMID- 7789970 TI - The L19 ribosomal protein gene (RPL19): gene organization, chromosomal mapping, and novel promoter region. AB - The intron-containing genes encoding rat and human ribosomal protein L19 (RPL19) have been cloned. The DNA sequences of the entire rat RPL19 gene and the 5' end of the human RPL19 gene have been determined. Sequence comparison of corresponding regions of the two genes reveals a striking interspecies homology in the 5' upstream region, outside the transcribed and coding regions. The transcriptional start sites of the two genes have been determined and are identical. Both rat and human RPL19 genes have 5' ends associated with CpG islands. A promoter deletion analysis of the rat RPL19 gene suggests that this promoter may differ from those of all previously characterized ribosomal protein genes in requiring far upstream sequences for efficient gene expression. By fluorescence in situ hybridization analysis, the position of the human RPL19 gene has been sublocalized to 17q11 and may be coamplified with the erbB-2 gene in human breast cancer cells. The similarities and differences between RPL19 and other previously characterized ribosomal protein genes are discussed. PMID- 7789971 TI - Molecular cloning of a cDNA and chromosomal localization of a human theta-class glutathione S-transferase gene (GSTT2) to chromosome 22. AB - Until recently the Theta-class glutathione S-transferases (GSTs) were largely overlooked due to their low activity with the model substrate 1-chloro-2,4 dinitrobenzene (CDNB) and their failure to bind to immobilized glutathione affinity matrices. Little is known about the number of genes in this class. Recently, Pemble et al. (Biochem J. 300: 271-276, 1994) reported the cDNA cloning of a human Theta-class GST, termed GSTT1. In this study, we describe the molecular cloning of a cDNA encoding a second human Theta-class GST (GSTT2) from a lambda gt11 human liver 5'-stretch cDNA library. The encoded protein contains 244 amino acids and has 78.3% sequence identity with the rat subunit 12 and only 55.0% identity with human GSTT1. GSTT2 has been mapped to chromosome 22 by somatic cell hybrid analysis. The precise position of the gene was localized to subband 22q11.2 by in situ hybridization. The absence of other regions of hybridization suggests that there are no closely related sequences (e.g., reverse transcribed pseudogenes) scattered throughout the genome and that if there are closely related genes, they must be clustered near GSTT2. Southern blot analysis of human DNA digested with BamHI shows that the size of the GSTT2 gene is relatively small, as the coding sequence falls within a 3.6-kb BamHI fragment. PMID- 7789972 TI - Murine chromosomal location of eight members of the hepatocyte nuclear factor 3/fork head winged helix family of transcription factors. AB - A 100-amino-acid DNA-binding motif, known as the winged helix, was first identified in the mammalian hepatocyte nuclear factor-3 (HNF-3) and Drosophila fork head family of transcription factors. Subsequently, more than 40 different genes that contain the winged helix motif have been identified. In the studies described here, we have determined the murine chromosomal location of eight members of this gene family, HFH-1, HFH-3, HFH-4, HFH-5, HFH-6, HFH-8, BF-1, and BF-2, by interspecific backcross analysis. These genes, designated HNF-3 fork head homolog 1 (Hfh1), Hfh3, Hfh4, Hfh5, Hfh6, Hfh8, Hfh9, and Hfh10, respectively, mapped to 6 different mouse autosomes and are thus well dispersed throughout the mouse genome. Based on this mapping information, we predict the chromosomal location of these genes in humans and discuss the potential of these genes as candidates for uncloned mouse mutations. PMID- 7789974 TI - Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus. AB - Infantile neuronal ceroid lipofuscinosis (INCL, CLN1) is a neurodegenerative disorder in which the biochemical defect is unknown. We earlier assigned the disease locus to chromosome 1p32 in the immediate vicinity of the highly informative HY-TM1 marker by linkage and linkage disequilibrium analysis. Here we report the construction of PFGE maps on the CLN1 region covering a total of 4 Mb of this relatively poorly mapped chromosomal region. We established the order of loci at 1p32 as tel-D1S57-L-myc-HY-TM1-rlf-COL9A2-D1S193-D1S6 2-D1S211-cen by combining data obtained from analysis of a chromosome 1 somatic cell hybrid panel, PFGE, and interphase FISH. We isolated YACs and constructed two separate YAC contigs, the loci L-myc, HY-TM1, rlf, and COL9A2 being present on a 1000-kb contig and the markers D1S193, D1S62, and D1S211 on a YAC contig spanning a maximum of 860 kb. Within the 1000-kb contig we were able to identify five CpG islands in addition to those associated with the earlier cloned genes. The YAC contigs as well as the physical map provide us with tools for the identification of the INCL gene. PMID- 7789973 TI - D20S16 is a complex interspersed repeated sequence: genetic and physical analysis of the locus. AB - The genomic structure of the D20S16 locus has been evaluated using genetic and physical methods. D20S16, originally detected with the probe CRI-L1214, is a highly informative, complex restriction fragment length polymorphism consisting of two separate allelic systems. The allelic systems have the characteristics of conventional VNTR polymorphisms and are separated by recombination (theta = 0.02, Zmax = 74.82), as demonstrated in family studies. Most of these recombination events are meiotic crossovers and are maternal in origin, but two, including deletion of the locus in a cell line from a CEPH family member, occur without evidence for exchange of flanking markers. DNA sequence analysis suggests that the basis of the polymorphism is variable numbers of a 98-bp sequence tandemly repeated with 87 to 90% sequence similarity between repeats. The 98-bp repeat is a dimer of 49 bp sequence with 45 to 98% identity between the elements. In addition, nonpolymorphic genomic sequences adjacent to the polymorphic 98-bp repeat tracts are also repeated but are not polymorphic, i.e., show no individual to individual variation. Restriction enzyme mapping of cosmids containing the CRI L1214 sequence suggests that there are multiple interspersed repeats of the CRI L1214 sequence on chromosome 20. The results of dual-color fluorescence in situ hybridization experiments with interphase nuclei are also consistent with multiple repeats of an interspersed sequence on chromosome 20. PMID- 7789975 TI - Region-specific cosmids and STRPs identified by chromosome microdissection and FISH. AB - A strategy for identifying short tandem repeat (STR)-containing cosmid clones from a specific chromosomal region is described. The approach is based on the use of uncloned, PCR-amplified DNA derived from chromosome microdissection and pooled groups of STR sequences as hybridization probes to screen a cosmid library. Cosmid clones that display a positive signal common to both hybridizations are then characterized for repeat length polymorphisms. This method has been applied to chromosome bands 17q12-q21, a region that includes a gene (BRCA1) involved in early onset familial breast and ovarian cancer. Of 1536 chromosome 17-specific cosmid clones tested, 38 were identified by the dual screening procedure. Fluorescence in situ hybridization revealed that 19 cosmids originated from the microdissected target region. Thirteen of the 19 cosmids were mapped between markers flanking the BRCA1 region and selected for further characterization. Tetranucleotide repeats were identified in 10 of these 13 cosmids. Primers designed for each marker were tested on a panel of 80 CEPH parents for allele sizes, frequencies, and observed heterozygosities. From these studies six polymorphic and one nonpolymorphic STRs were identified. A similar approach should be applicable for screening whole genomic or chromosome-specific cosmid libraries in efforts to isolate new polymorphic markers from any chromosomal region of interest. PMID- 7789976 TI - Genetic mapping of the spinocerebellar ataxia 2 (SCA2) locus on chromosome 12q23 q24.1. AB - A refined genetic map of the spinocerebellar ataxia 2 locus was constructed through linkage and haplotype analysis of 11 large pedigrees from the Holguin SCA2 family collective. Three-point analysis makes a localization of the SCA2 mutation in the 6-cM interval D12S84-D12S79 likely. This is consistent with haplotype results indicating a crossover event between two branches of the SCA2 family Rs and placing the mutation on the telomeric side of D12S84. The microsatellite D12S105 within this interval shows a peak two-point lod score of Z = 16.14 at theta = 0.00 recombination and complete linkage disequilibrium among affected individuals. These data together with the observation of a common disease haplotype among all family ancestors support the notion of an SCA2 founder effect in Holguin province. PMID- 7789977 TI - Analysis of the dopamine receptor family in the compact genome of the puffer fish Fugu rubripes. AB - The genome of the puffer fish, Fugu rubripes (Fugu), is approximately 400 Mb, 7.5 times smaller than that of human. We have isolated four dopamine receptor-like genes from Fugu genomic DNA. These genes show high sequence and structural homology to the known dopamine receptor genes, although, in contrast to previously described genes from this species, the intron size is comparable to that in human. The 5' noncoding exons of the D2/D3 dopamine receptor-like genes is described and compared to that in human. The high gene density of Fugu is shown by the close proximity of a cystatin-like gene 1503 bp from the dopamine receptor gene D222. We propose that the compact genome of Fugu can serve as a model for identifying gene family members directly from genomic DNA. PMID- 7789978 TI - A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1. AB - We describe a detailed physical map of human chromosome 11, extending from the distal part of p13 through the entirety of p14 to proximal p15.1. The primary level of mapping is based on chromosome breakpoints that divide the region into 20 intervals. At higher resolution YACs cover approximately 12 Mb of the region, and in many places overlapping cosmids are ordered in contiguous arrays. The map incorporates 18 known genes, including precise localization of the GTF2H1 gene encoding the 62-kDa subunit of TFIIH. We have also localized four expressed sequences of unknown function. The physical map incorporates genetic markers that allow relationships between physical and genetic distance to be examined, and similarly includes markers from a radiation hybrid map of 11. The cytogenetic location of cosmids has been examined on high-resolution banded chromosomes by fluorescence in situ hybridization, and FLpter values have been determined. The map therefore fully integrates physical, genic, genetic, and cytogenetic information and should provide a robust framework for the rapid and accurate assignment of new markers at a high level of resolution in this region of 11p. PMID- 7789979 TI - The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney. AB - After herpes simplex virus (HSV) infection, the viral regulatory protein VP16 activates transcription of the HSV immediate-early promoters by directing complex formation with two cellular proteins, the POU-homeodomain transcription factor Oct-1 and the host cell factor HCF. The function of HCF in uninfected cells is unknown. Here we show by fluorescence in situ hybridization and somatic cell hybrid analysis that the gene encoding human HCF, HCFC1, maps to the q28 region of the X chromosome. Yeast artificial chromosome and cosmid mapping localizes the HCFC1 gene within 100 kb distal of the renal vasopressin type-2 receptor (V2R) gene and adjacent to the renin-binding protein gene (RENBP). The HCFC1 gene is apparently unique. HCF transcripts and protein are most abundant in fetal and placental tissues and cell lines, suggesting a role in cell proliferation. In adults, HCF protein is abundant in the kidney, but not in the brain, a site of latent HSV infection and where HCF levels may influence progression of HSV infection. PMID- 7789981 TI - Comparative mapping of human alphoid sequences in great apes using fluorescence in situ hybridization. AB - Twenty-seven human alphoid DNA probes have been hybridized in situ to metaphase spreads of the common chimpanzee (PTR), the pigmy chimpanzee (PPA), and the gorilla (GGO) to investigate the evolutionary relationship between the centromeric regions of the great ape chromosomes. The surprising results showed that the vast majority of the probes did not recognize their corresponding homologous chromosomes. Alphoid sequences belonging to the suprachromosomal family 1 (chromosomes 1, 3, 5, 6, 7, 10, 12, 16, and 19) yielded very heterogeneous results: some probes gave intense signals, but always on nonhomologous chromosomes; others did not produce any hybridization signal. Almost all probes belonging to the suprachromosomal family 2 (chromosomes 2, 4, 8, 9, 13, 14, 15, 18, 20, 21, and 22) recognized a single chromosome: chromosome 11 (phylogenetic IX) in PTR and PPA and chromosome 19 (phylogenetic V) in GGO. Localization of probes of suprachromosomal family 3 (chromosomes 1, 11, 17, and X) was found to be substantially conserved in PTR and PPA, but not in GGO. Probe pDMX1, specific for the human X chromosome, was the only sequence detecting its corresponding chromosome in all three species. PPA chromosomes I, IIp, IIq, IV, V, VI, and XVIII were never labeled, even under low-stringency hybridization conditions, by the 27 alphoid probes used in this study. These results, with particular reference to differences found in the two related species PTR and PPA, suggest that alphoid centromeric sequences underwent a very rapid evolution. PMID- 7789980 TI - Molecular cloning and chromosomal localization of a pseudogene related to the human acyl-CoA binding protein/diazepam binding inhibitor. AB - The acyl-CoA binding protein (ACBP) and the diazepam binding inhibitor (DBI) or endozepine are independent isolates of a single 86-amino-acid, 10-kDa protein. ACBP/DBI is highly conserved between species and has been identified in several diverse organisms, including human, cow, rat, frog, duck, insects, plants, and yeast. Although the genomic locus has not yet been cloned in humans, complementary DNA clones with different 5' ends have been isolated and characterized. These cDNA clones appear to be encoded by a single gene. However, Southern blot analyses, in situ hybridizations, and somatic cell hybrid chromosomal mapping all suggest that there are multiple ACBP/DBI-related sequences in the genome. To identify potential members of this gene family, degenerate oligonucleotides corresponding to highly conserved regions of ACBP/DBI were used to screen a human genomic DNA library using the polymerase chain reaction. A novel gene, DBIP1, that is closely related to ACBP/DBI but is clearly distinct was identified. DBIP1 bears extensive sequence homology to ACBP/DBI but lacks the introns predicted by rat and duck genomic sequence studies. A 1-base deletion in the coding region results in a frameshift and, along with the absence of introns and the lack of a detectable transcript, suggests that DBIP1 is a pseudogene. ACBP/DBI has previously been mapped to chromosome 2, although this was recently disputed, and a chromosome 6 location was suggested. We show that ACBP/DBI is correctly placed on chromosome 2 and that the gene identified on chromosome 6 is DBIP1. PMID- 7789982 TI - Treatment of cells with alkaline borate buffer extends the capability of interphase FISH mapping. AB - Interphase fluorescence in situ hybridization (FISH) has been shown to be a means to map DNA sequences relative to each other in the 100 kb to 1-2 Mb genomic separation range. At distances below 0.1 Mb, probe sites are infrequently resolved in interphase chromatin. In the 0.1- to 1-Mb range, interphase chromatin can be modeled as a freely flexible chain. The mean square interphase distance between two probes is proportional to the genomic separation between the probes on the linear DNA molecule. Above 1-2 Mb, the relationship between interphase distance and genomic separation changes abruptly and appears to level off. We have used alkaline-borate treatment to expand the capability of interphase FISH mapping. We show here that alkaline-borate treatment increases nuclear diameter, the interphase distance between probes on homologous chromosomes, and the distance between probes on the same chromosome. We also show that the mean square distance between hybridization sites in borate-treated nuclei is proportional to genomic separation up to 4 Mb. Thus, alkaline-borate treatment enhances the capability of interphase FISH mapping by increasing the absolute distance between probes and extending the range of the simple relationship between interphase distance and genomic separation. PMID- 7789983 TI - Cloning, characterization, and chromosomal localization to 4p16 of the human gene (LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein and structural comparison with the murine gene coding for the 44-kDa heparin-binding protein. AB - We report the molecular cloning of the human gene (symbol LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein (A2MRAP), as well as the gene coding for the 44-kDa heparin-binding protein (HBP-44), its murine counterpart. For both, genomic cosmid clones were isolated, and for the human gene a bacteriophage P1 clone containing the entire A2MRAP gene was also retrieved. The genes were characterized after subcloning: in both species, the known coding part of the cDNA is encoded by eight exons, and the position of the boundaries of the exons was conserved. The human LRPAP1 locus was assigned to chromosome 4 by PCR of human-hamster hybrid cell lines and by fluorescence in situ hybridization to band 4p16.3. This maps closely to the variable constitutional deletions of the short arm of chromosome 4, observed cytogenetically in patients with the Wolf Hirschhorn syndrome. Metaphase spreads of two such patients were analyzed by fluorescence in situ hybridization with an LRPAP1 genomic probe. The first patient, with karyotype 46,XY,del4(p14-p16.1), had retained both copies of the LRPAP1 gene. In contrast, the other patient, with karyotype 46,XY,del4(p15.3 pter), displayed no signal for LRPAP1 on the deleted chromosome. PMID- 7789984 TI - Genomic structure of SAS, a member of the transmembrane 4 superfamily amplified in human sarcomas. AB - SAS is a recently identified member of the transmembrane 4 superfamily (TM4SF) that is frequently amplified in human sarcomas. To further its characterization and to confirm its classification, the genomic structure of the SAS gene was determined. The SAS gene covers approximately 3.2 kb of DNA. It contains six exons within its translated region, three of which are highly conserved in the TM4SF. 5' to the translation start site are two putative transcription start sites, two CCAAT consensus sequences, and potential binding sites for both Sp1 and ATF transcription factors. Comparison of SAS organization to human ME491, CD9, and CD53 and murine CD53 and TAPA-1 confirms that SAS is a member of this family of genes and is consistent with the theory that these genes arose through duplication and divergent evolution. PMID- 7789986 TI - Identification and characterization of a second mouse Nramp gene. AB - The Nramp gene was isolated as a candidate for the host resistance locus Bcg/Ity/Lsh, which controls natural resistance of mice to several types of infections. We have isolated by cross-hybridization cDNA clones corresponding to a second mouse Nramp gene, which we designate Nramp2. Nucleotide and predicted amino acid sequence analyses of full-length cDNA clones for Nramp2 indicate that this novel Nramp protein is closely homologous to the previously described Nramp and that the two genes form part of a small gene family. The two Nramp proteins encode integral membrane proteins that share 63% identical residues and an overall homology of 78%. They share very similar secondary structure, including identical hydropathy profiles and predicted membrane organization, with a minimum of 10 and most probably 12 transmembrane domains, a cluster of predicted N-linked glycosylation sites, and a consensus transport motif. Analysis of the distribution of Nramp2 mRNA transcripts in normal mouse tissues by Northern blotting revealed that the Nramp2 gene produces several mRNAs, including prominent 3.3- and 2.3-kb species generated by the use of alternative polyadenylation signals. In contrast to the previously described macrophage specific Nramp gene, Nramp2 mRNAs were found to be expressed at low levels in all tissues tested. Using a polymorphic (GT)26 dinucleotide repeat identified in the 3' untranslated region of the mRNA, we have mapped the Nramp2 gene to the distal part of mouse chromosome 15 between markers D15Mit41 and D15Mit15, with the gene order and intergene distance (in cM): centromere-56.1-D15Mit41-(1 +/- 1)-Nramp2 (5 +/- 2)-D15Mit15. PMID- 7789985 TI - The human osmoregulatory Na+/myo-inositol cotransporter gene (SLC5A3): molecular cloning and localization to chromosome 21. AB - A human Na+/myo-inositol cotransporter (SLC5A3) gene was cloned; sequencing revealed a single intron-free open reading frame of 2157 nucleotides. Containing 718 amino acid residues, the predicted protein is highly homologous to the product of the canine osmoregulatory SLC5A3 gene. The SLC5A3 protein is number 3 of the solute carrier family 5 and was previously designated SMIT. Using fluorescence in situ hybridization, the human SLC5A3 gene was localized to band q22 on chromosome 21. Many tissues including brain demonstrate gene expression. The inability of a trisomic 21 cell to downregulate expression of three copies of this osmoregulatory gene could result in increased flux of both myo-inositol and Na+ across the plasma membrane. The potential consequences include perturbations in the cell membrane potential and tissue osmolyte levels. The SLC5A3 gene may play a role in the pathogenesis of Down syndrome. PMID- 7789987 TI - Development and physical analysis of YAC contigs covering 7 Mb of Xp22.3-p22.2. AB - A total of 54 YAC clones have been isolated from the region of Xp22.2-p22.3 extending from the amelogenin gene locus to DXS31. Restriction analysis of these clones in association with STS contenting and end clone analysis has facilitated the construction of 6 contigs covering a total of 7 Mb in which 20 potential CpG islands have been located. Thirty new STSs have been developed from probe and YAC end clone sequences, and these have been used in the analysis of patients suffering from different combinations of chondrodysplasia punctata, mental retardation, X-linked ichthyosis, and Kallmann syndrome. The results suggest that (1) the gene for chondrodysplasia punctata must lie between the X chromosome pseudoautosomal boundary (PABX) and DXS1145; (2) a gene for mental retardation lies between DXS1145 and the sequence tagged site GS1; and (3) the gene for ocular albinism type 1 lies proximal to the STS G13. The CpG islands within the YAC contigs constitute valuable markers for the potential positions of genes. Genes found associated with any of these potential CpG islands would be possible candidates for the disease genes mentioned above. PMID- 7789988 TI - Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). AB - There is increasing evidence that neutrophins and their receptors play an important role in regulating development of both the central and the peripheral nervous systems. Human TRK-A (NTRK1) and TRK-C (NTRK3) have been cloned and sequenced, but only a truncated form of human TRK-B has been published. Therefore, we isolated complementary DNAs spanning the entire coding region of both human full-length and truncated forms of TRK-B from human brain cDNA libraries. Human full-length TRK-B codes for a protein of 822 amino acid residues. The putative mature peptide sequence is 49% homologous to human TRK-A and 55% to full-length human TRK-C, with 40% amino acid identify among TRK-A, -B, and -C. Nine of 13 cysteine residues, 4 of 12N-glycosylation sites in the extracellular domain, and 10 of 13 tyrosine residues in the intracellular domain are conserved among human TRK-A, -B, and -C. There is a cluster of 10 serine residues in the juxtamembrane region of TRK-B that is absent in TRK-A. Two major sizes of TRK-B transcripts were expressed in human brain. Northern blot analysis using probes specific for the extracellular or the tyrosine kinase domain revealed that the 9.5-kb band encodes the full-length TRK-B mRNA and the 8.0-kb band encodes the truncated form of TRK-B mRNA. By fluorescence in situ hybridization and somatic cell hybrid mapping, the human TRK-B gene was localized to chromosome 9q22.1. PMID- 7789989 TI - Genomic sequence comparison of the human and mouse XRCC1 DNA repair gene regions. AB - The XRCC1 (X-ray repair cross complementing) gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The human gene maps to chromosome 19q13.2, and the mouse homologue maps to the syntenic region on chromosome 7. Two cosmids (approximately 38 kb each) containing the human and mouse genes were sequenced to an average 8 fold clonal redundancy. The XRCC1 gene spans a genomic distance of 26 kb in mouse and 31.9 kb in human. Both genes contain 17 exons, are 84% identical within the coding regions, and are 86% identical at the amino acid sequence level. Intron and exon lengths are highly conserved. For the human cosmid, a total of 43 Alu repetitive elements are present, a density of 1.1 Alu/kb, but due to clustering, the local density is as high as 1.8 Alu/kb. In addition, we observed a statistically significant bias for insertion of these elements in the 3'-5' orientation relative to the direction of XRCC1 transcription, predominantly in the second and third introns. This bias may indicate that XRCC1 is more accessible to Alu retroposition events during transcription than genes not expressed during spermatogenesis. The density of B1 and B2 elements in the mouse is 0.4/kb, integrated primarily in the 5'-3' orientation. The human chromosome 19 specific minisatellite PE670 was present in the same orientation in 3 introns in the human gene, and a similar repeat was found at 3 different locations in the mouse cosmid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7789990 TI - CLONEPLACER: a software tool for simulating contig formation for ordered shotgun sequencing. AB - This communication describes a software tool that enables one to simulate large scale regional mapping using an ordered shotgun sequencing approach. The analysis routines that are provided yield an estimate of the depth of coverage of the physical map, the largest contig formed, and the number of gaps remaining at any given juncture in the project. A detailed listing describing the span of each contig within the physical map is also presented. This provides an a priori means of estimating the resources that will be required to undertake any megabase mapping or sequencing project. CLONEPLACER provides the much needed guide to deriving the optimal strategy. PMID- 7789991 TI - Chromosomal localization of mitochondrial transcription factor A (TCF6), single stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involved in mitochondrial biogenesis. AB - By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA. PMID- 7789993 TI - Localization of the human phosphatidylinositol-specific phospholipase c beta 3 gene (PLCB3) within chromosome band 11q13. AB - In course of the molecular characterization of a human extragonadal germ cell tumor (EGCT)-associated chromosomal translocation, we identified YACs and cosmids from the 11q13 region. The endclone of one of these YACs appeared to contain a stretch of DNA homologous to part of the human phosphatidylinositol-specific phospholipase C beta 3 gene (PLCB3). Since we considered PLCB3 a candidate gene for these EGCTs, we set out to clone the PLCB3 cDNA, from which the 5' end was still missing, and performed Northern and Southern blot analyses. The localization of PLCB3 to 11q13 was confirmed. In addition, we were able to exclude the gene from involvement in EGCT development. PMID- 7789992 TI - Homologs of Drosophila Fushi-Tarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33. AB - SF-1, a nuclear receptor that regulates gene expression of the cytochrome P450 steroid hydroxylases, and ELP, an embryonal protein that suppresses expression of the Moloney murine leukemia virus LTR, are isoforms transcribed from the same gene by alternative promoter usage and splicing. This gene is the mammalian homolog of the Drosophila fushi-tarazu factor 1 (FTZ-F1) gene. We have mapped the mouse gene Ftzf1 to the proximal quarter of Chr 2 by a linkage analysis using interspecific backcross mice, and its human homolog FTZ1 to Chr 9q33 by fluorescence in situ hybridization. The mouse and human genes are located in the homologous regions of mouse Chr 2 and human Chr 9, respectively. PMID- 7789995 TI - The beta crystallin genes on human chromosome 22 define a new region of homology with mouse chromosome 5. AB - The human beta crystallin genes CRYBB2, CRYBB2P1, CRYBB3, and CRYBA4 are located in 22q11.2. Using interspecific backcross analysis, we mapped the mouse homologues of CRYBB2, CRYBB3, and CRYBA4 (i.e., Crybb2, Crybb3, and Cryba4) to the central region of mouse chromosome 5. The homologue of human CRYBB2P1 is absent in mouse. These assignments define a new region of homology in human and mouse. PMID- 7789994 TI - Expanded CTG triplet blocks from the myotonic dystrophy gene create the strongest known natural nucleosome positioning elements. AB - Expanded blocks of repeating nucleotide triplets have been found in or near genes associated with several human diseases. In the case of myotonic dystrophy, a block of repeating CTG trinucleotides is located downstream of the gene, and expansions of this block to repeats of n = 100 or more are frequently found in afflicted individuals. Using electron microscopy, we recently demonstrated that these blocks form unusually stable nucleosomes. Here, competitive nucleosome reconstitution was employed to measure the energetics of nucleosome formation over CTG repeat blocks of n = 75 and n = 130. These values were compared to the Xenopus borealis somatic 5S RNA gene, previously one of the strongest known natural nucleosome positioning elements. It is shown that DNA fragments containing 75 and 130 CTG repeats are 6 and 9 times stronger in nucleosome formation, respectively, than the 5S RNA gene. These findings suggest that expanded CTG blocks may profoundly alter local chromatin structure. PMID- 7789997 TI - Chromosome mapping of human (ZNF147) and mouse genes for estrogen-responsive finger protein (efp), a member of the RING finger family. AB - We have previously identified an estrogen-responsive gene, efp (estrogen responsive finger protein), that encodes a putative zinc finger protein (Proc. Natl. Acad. Sci. USA 90: 11117-11121, 1993). The efp protein has a RING finger, a variant type of zinc finger motif, B1 box, and B2 box, each having a pair of zinc fingers, present in a family of apparent DNA-binding proteins. Some members of this family have transformation capabilities when found in chromosomal translocations. Chromosome mapping of the efp gene by fluorescence in situ hybridization reveals that human EFP (ZNF147) is located at 17q23.1 and that mouse Efp is located at 11C. These results provide additional evidence that the mouse 11C region displays conserved synteny with the 17q23.1 region of the human genome. PMID- 7789996 TI - Mapping of ribosomal protein S3 and internally nested snoRNA U15A gene to human chromosome 11q13.3-q13.5. AB - The mammalian ribosome is a massive structure composed of 4 RNA species and about 80 different proteins. One of these ribosomal proteins, S3, appears to function not only in translation but also as an endonuclease in repair of UV-induced DNA damage. Moreover, the first intron of human RPS3 transcripts is processed to generate U15A, a small nucleolar RNA. We localized the nested RPS3/U15A genes to the immediate vicinity of D11S356 and D11S533 on human chromosome 11q13.3-q13.5 using a combination of somatic cell hybrid analysis, fluorescence in situ hybridization, and YAC/STS content mapping. These findings add to the evidence that genes encoding ribosomal proteins are scattered about the human genome. PMID- 7789998 TI - Localization of an epithelial-specific receptor kinase (EDDR1) to chromosome 6q16. AB - A protein receptor tyrosine kinase (EDDR1) has been isolated from a complementary DNA library of SKOV-3, an epithelial ovarian cancer cell line. The primary structure of the predicted amino acid sequence of the protein shows a novel N terminal region that has homology to a factor VIII-like domain. The C-terminal catalytic domain has all of the canonical sequence motifs of a receptor tyrosine kinase with homology to the TRK-2H protein (49%), which suggests that it is a type II receptor. It is expressed in epithelial cells of several tissues. To determine the chromosomal localization of the gene, somatic cell hybrids were analyzed by PCR amplification using oligonucleotide primers specific for EDDR1. Segregation was observed to a hybrid containing human chromosome 6. Cosmids for EDDR1 were isolated from a human chromosome 6 cosmid library and were shown by fluorescence in situ hybridization to map to 6q16. PMID- 7789999 TI - Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization. AB - Multiple human dihydrodiol dehydrogenases and human chlordecone reductase belong to the aldoketo reductase superfamily. These two enzymes are involved in the metabolism of xenobiotics, such as polycyclic aromatic hydrocarbons and pesticides. Recently we have isolated three closely related genes encoding two dihydrodiol dehydrogenases (DDH1 and DDH2) and the chlordecone reductase (CHDR). Mapping of the location of the genes was performed using the polymerase chain reaction using gene-specific primers to amplify gene sequences in human/hamster hybrid DNA. All three genes were found to be located on chromosome 10. In situ hybridization using a lambda clone as the probe further confirmed regional localization at 10p14-p15. PMID- 7790000 TI - Tandem arrangement of the closely linked desmoglein genes on human chromosome 18. AB - The desmogleins, together with the desmocollins, both members of the cadherin superfamily, are the adhesive proteins of the desmosome type of cell junction, characteristically found in epithelial cells. Three different human desmoglein isoforms are encoded by separate genes (DSG1, DSG2, and DSG3) located on chromosome 18q12.1. DSG2 has been shown to be the most widely expressed in all desmosome-containing tissues, whereas DSG1 and DSG3 are expressed only in certain tissues, mostly stratified squamous epithelia. The desmoglein isoforms are expressed in a stratification-related manner in human epidermis, DSG1 being suprabasally expressed and DSG3 at a lower level, while DSG2 expression is weak and basal. Yeast artificial chromosome clones carrying all three known human desmoglein genes have now been isolated. The smallest clone containing all three DSG genes was 275 kb, and the three desmoglein genes were clustered within a region of less than 150 kb. From the types of clone obtained and from restriction enzyme analysis the order of the DSG genes and their orientation was deduced to be 5'-DSG1-DSG3-DSG2-3'. There thus appears to be some correspondence between the order of DSG genes and their expression within tissues, raising the intriguing possibility that the organization of the desmoglein gene cluster is required for properly regulated gene expression. PMID- 7790001 TI - Mapping of the human protein kinase C-theta (PRKCQ) gene locus to the short arm of chromosome 10 (10p15) by FISH. PMID- 7790002 TI - Localization of the human zipper protein kinase gene (ZPK) to chromosome 12q13 by fluorescence in situ hybridization and somatic cell hybrid analysis. PMID- 7790003 TI - Dinucleotide repeat polymorphism at the human chromosome 11p telomere (D11S2071). PMID- 7790004 TI - Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridization. PMID- 7790005 TI - Mapping of the mouse homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4. PMID- 7790006 TI - Localization of the adenosine A2b receptor subtype gene (ADORA2B) to chromosome 17p11.2-p12 by FISH and PCR screening of somatic cell hybrids. PMID- 7790007 TI - Judgments of azimuth and elevation as a function of monoscopic and binocular depth cues using a perspective display. AB - The purpose of this study was to investigate the use of three-dimensional display formats for judgments of spatial information using an exocentric frame of reference. Eight subjects judged the azimuth and elevation that separated two computer-generated objects using either a perspective or stereoscopic display. Errors, which consisted of the difference in absolute value between the estimated and actual azimuth or elevation, were analyzed as the response variable. The data indicated that the stereoscopic display resulted in more accurate estimates of elevation, especially for images aligned approximately orthogonally to the viewing vector. However, estimates of relative azimuth direction were not improved by use of the stereoscopic display. Furthermore, it was shown that the effect of compression resulting from a 45-deg computer graphics eye point elevation produced a response bias that was symmetrical around the horizontal plane of the reference cube, and that the depth cue of binocular disparity provided by the stereoscopic display reduced the magnitude of the compression errors. Implications of the results for the design of spatial displays are discussed. PMID- 7790008 TI - Situation awareness in anesthesiology. AB - Situation awareness has primarily been confined to the aviation field. We believe that situation awareness is an equally important characteristic in the complex, dynamic, and risky field of anesthesiology. We describe three aspects of situations of which the decision maker must remain aware: subtle cues, evolving situations, and special knowledge elements. We provide examples of real or simulated anesthesia situations in which situation awareness is clearly involved in the provision of optimal patient care, and we map the elements of situation awareness onto a cognitive process model of the anesthesiologist. Finally, we consider how situation awareness can be further investigated and taught in this medical domain using anesthesia simulators and analyses of real cases. The study of situation awareness in anesthesiology may provide a good example of the wider application of the concept of situation awareness to nonaerospace environments. PMID- 7790009 TI - Intracranial pressure dynamics in patients with acute brain damage: a critical analysis with the aid of a mathematical model. AB - The time pattern of intracranial pressure (ICP) in response to typical clinical tests (i.e., bolus injection and bolus withdrawal of 1 to 4 mL of saline in the craniospinal space) was studied in 18 patients with acute brain damage by means of a mathematical model. The model includes the main biomechanical factors assumed to affect intracranial pressure, particularly cerebrospinal fluid (CSF) dynamics, intracranial compliance, and cerebral hemodynamics. Best fitting between model simulation curves and clinical tracings was achieved using the Powell minimization algorithm and a least-square criterion function. The simulation results demonstrate that, in most patients, the ICP time pattern cannot be explained merely on the basis of CSF dynamics but also requires consideration of the contribution of cerebral hemodynamics and blood volume alterations. In particular, only in a few patients (about 40% of total) the ICP monotonically returns toward baseline following the clinical maneuver. In most of the examined cases (about 60%), ICP exhibits an anomalous response to the same maneuver, characterized by a delayed increase after bolus injection and a delayed decrease after withdrawal. The model is able to explain these responses, imputing them to active intracranial blood volume changes induced by mechanisms controlling cerebral blood flow. Finally, the role of the main intracranial biomechanical parameters in the genesis of the ICP time pattern is discussed and a comparison with previous theoretical studies performed. PMID- 7790010 TI - Machine learning in control of functional electrical stimulation systems for locomotion. AB - Two machine learning techniques were evaluated for automatic design of a rule based control of functional electrical stimulation (FES) for locomotion of spinal cord injured humans. The task was to learn the invariant characteristics of the relationship between sensory information and the FES-control signal by using off line supervised training. Sensory signals were recorded using pressure sensors installed in the insoles of a subject's shoes and goniometers attached across the joints of the affected leg. The FES-control consisted of pulses corresponding to time intervals when the subject pressed on the manual push-button to deliver the stimulation during FES-assisted ambulation. The machine learning techniques used were the adaptive logic network (ALN) [1] and the inductive learning algorithm (IL) [2]. Results to date suggest that, given the same training data, the IL learned faster than the ALN, while both performed the test rapidly. The generalization was estimated by measuring the test errors and it was better with an ALN, especially if past points were used to reflect the time dimension. Both techniques were able to predict future stimulation events. An advantage of the ALN over the IL was that ALN's can be retrained with new data without losing previously collected knowledge. The advantages of the IL over the ALN were that the IL produces small, explicit, comprehensible trees and that the relative importance of each sensory contribution can be quantified. PMID- 7790011 TI - Epicardial cardiac source-field behavior. AB - The accurate determination of the spatial distribution of cardiac electrophysiological state is essential for the mechanistic assessment of cardiac arrhythmias in both clinical and experimental cardiac electrophysiological laboratories. This paper describes three fundamental cardiac source-field relationships: 1) activation fields, 2) electrotonic fields, and 3) volume conductor fields. The three cases are described analytically and illustrated with experimentally obtained canine cardiac recordings that capitalize on a recently formulated technique for in vivo cardiac transmembrane current estimation. PMID- 7790012 TI - Predicting cardiothoracic voltages during high energy shocks: methodology and comparison of experimental to finite element model data. AB - Finite element modeling has been used as a method to investigate the voltage distribution within the thorax during high energy shocks. However, there have been few quantitative methods developed to assess how well the calculations derived from the models correspond to measured voltages. In this paper, we present a methodology for recording thoracic voltages and the results of comparisons of these voltages to those predicted by finite element models. We constructed detailed 3-D subject-specific thorax models of six pigs based on their individual CT images. The models were correlated with the results of experiments conducted on the animals to measure the voltage distribution in the thorax at 52 locations during synchronized high energy shocks. One transthoracic and two transvenous electrode configurations were used in the study. The measured voltage values were compared to the model predictions resulting in a correlation coefficient of 0.927 +/- 0.036 (average +/- standard deviation) and a relative rms error of 22.13 +/- 5.99%. The model predictions of voltage gradient within the myocardium were also examined revealing differences in the percent of the myocardium above a threshold value for various electrode configurations and variability between individual animals. This variability reinforces the potential benefit of patient-specific modeling. PMID- 7790013 TI - A three-dimensional finite element model of human transthoracic defibrillation: paddle placement and size. AB - A detailed 3-D finite element model of the conductive anatomy of the human thorax has been constructed to quantitatively assess the current density distribution produced in the heart and thorax during transthoracic defibrillation. The model is based on a series of cross-sectional CT scans and incorporates isotropic conductivities for eight tissues and an approximation of the anisotropic conductivity of skeletal muscle. Current density distributions were determined and compared for four paddle pairs and two paddle sizes. Our results show that the myocardial current density distributions resulting from a defibrillation shock were fairly uniform for the paddle pairs and sizes examined in this study. Specific details of the spatial distribution of the current density magnitudes in the heart were found to depend on paddle placement and size. When the minimum current necessary to defibrillate was delivered, the maximum myocardial current density produced with any of the paddle sizes and positions examined was less than four times the minimum current density necessary to render a myocyte in a fibrillating heart inexcitable, and less than 40% of the damage threshold. These results suggest that common clinically used defibrillation paddle positions have a safety margin as large as 2.5 for current and approximately 6 for energy. PMID- 7790014 TI - A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart. AB - Atrial fibrillation (AF) is a common clinical problem, associated with considerable morbidity and mortality, for which effective management strategies have yet to be devised. The absence of objective measures to guide selection of antiarrhythmic drug therapy for maintenance of sinus rhythm leaves only clinical endpoints (either beneficial or detrimental) for assessment of drug action, with occasional catastrophic consequences. As part of an attempt to provide an objective framework for the assessment of antiarrhythmic drug action on the electrophysiologic determinants of atrial fibrillation, we have developed a measure of the spatial organization of atrial activation processes during atrial fibrillation. By recording activation sequences at multiple equally spaced locations on the endocardial surface of the atria during atrial fibrillation in humans and determining the degree of correlation between these activation sequences as a function of distance, we have been able to construct spatial correlation functions for atrial activation. We have found that atrial activation remains well-correlated, independent of distance during normal sinus rhythm and atrial flutter. During atrial fibrillation, correlation decays monotonically with distance and the space-constant for this decay may be used to describe the relative spatial organization of atrial fibrillation. We provide examples of the impact of antiarrhythmic agents on the space-constant and suggest that assessment of the relative spatial organization of atrial activation using this methodology may potentially provide an objective framework to guide therapy in patients with AF. PMID- 7790015 TI - Use of sonomicrometry and multidimensional scaling to determine the three dimensional coordinates of multiple cardiac locations: feasibility and initial implementation. AB - We describe a new method which uses sonomicrometry and the statistical technique of multidimensional scaling (MDS) to measure the three-dimensional (3-D) coordinates of multiple cardiac locations. We refer to this new method as sonomicrometry array localization (SAL). The new method differs from standard sonomicrometry in that each piezoelectric transducer element is used as both transmitter and receiver and the set of intertransducer element distances is measured. MDS calculates the 3-D coordinates of each sonomicrometry transducer element from the set of intertransducer element distances. The feasibility of this new method was tested with mathematical simulations which demonstrated the ability of MDS to compensate for signal error and missing intertransducer element distances. We describe the design elements of a modified digitally controlled sonomicrometer in which a single transducer element can sequentially broadcast to as many as eight receiver elements. That design is used to validate SAL in a water bath and in ex vivo and living hearts. Correlation with caliper measurement in the water bath (y int. = 3.91 +/- 3.36 mm, slope = 1.04 +/- 0.05, r2 = 0.969 +/- 0.027) and with radiography in ex vivo (y int. = -0.87 +/- 0.92 mm, slope = 0.97 +/- 0.02, r2 = 0.960 +/- 0.023) and in vivo hearts (y int. = 2.98 +/- 2.59 mm, slope = 1.01 +/- 0.06, r2 = 0.953 +/- 0.031) was excellent. Sonomicrometry array localization is able to accurately measure the 3-D coordinates of multiple cardiac locations. It can potentially measure myocardial deformation and remodeling after ischemic or valvular injury. PMID- 7790016 TI - Action potentials of curved nerves in finite limbs. AB - Previous simulations of volume-conducted nerve-fiber action-potentials have modeled the limb as semi-infinite or circularly cylindrical, and the fibers as straight lines parallel to the limb surface. The geometry of actual nerves and limbs, however, can be considerably more complicated. This paper presents a general method for computing the potentials of fibers with arbitrary paths in arbitrary finite limbs. It involves computing the propagating point-source response (PPSR), which is the potential arising from a single point source (dipole or tripole) travelling along the fiber. The PPSR can be applied to fibers of different conduction velocities by simple dilation or compression. The method is illustrated for oblique and spiralling nerve fibers. Potentials from oblique fibers are shown to be different for orthodromic and antidromic propagation. Such results show that the straight-line models are not always adequate for nerves with anatomical amounts of curvature. PMID- 7790017 TI - Selective minimum-norm solution of the biomagnetic inverse problem. AB - A new multidipole estimation method which gives a sparse solution of the biomagnetic inverse problem is proposed. This solution is extracted from the basic feasible solutions of linearly independent data equations. These feasible solutions are obtained by selecting exactly as many dipole-moments as the number of magnetic sensors. By changing the selection, we search for the minimum-norm vector of selected moments. As a result, a practically sparse solution is obtained; computer-simulated solutions for Lp-norm (p = 2, 1, 0.5, 0.2) have a small number of significant moments around the real source-dipoles. In particular, the solution for L1-norm is equivalent to the minimum-L1-norm solution of the original inverse problem. This solution can be uniquely computed by using Linear Programming. PMID- 7790019 TI - Performance of above elbow body-powered prostheses in visually guided unconstrained motion tasks. AB - The "classical" body-powered above elbow arm prosthesis continues to be used by a large majority of arm prosthesis users, even though many more modern devices are available. This paper presents a set of experiments designed to compare performance of unimpaired arms and body-powered prostheses of six unilateral amputees. The experiments were designed to measure quantitatively how well the body-powered prosthesis can be used to perform free-motion tasks, as well as to study the qualitative features of movement common to both the prosthesis and unimpaired arm. It was found that regular peaks in velocity were common to both the unimpaired arm and prosthesis movements, suggesting that movements were composed of a sequence of successive actions. In addition, it was found that the body-powered prosthesis generally required more movements than the unimpaired arm to meet an accuracy constraint and could not keep up with the unimpaired arm when a speed constraint was imposed, even though the body-powered prosthesis was able to match the unimpaired arm in a simple nondynamic task. PMID- 7790018 TI - Evaluation of MUAP shape irregularity--a new concept of quantification. AB - A coefficient for quantifying the shape irregularities of the motor unit action potential (MUAP) is introduced. This coefficient is defined as the "length" of action potential curve normalized by the signal's amplitude in such a way that it is independent on duration and amplitude. It characterizes only the MUAP shape. The irregularity coefficient may be used to measure the deviations of the potential from the normal MUAP. The properties of this coefficient and its relation to the conventional parameters describing MUAP shape, viz the number of phases and turns is discussed. The examples of classification of real signals according to this coefficient are presented. PMID- 7790020 TI - A 32-electrode data collection system for electrical impedance tomography. AB - A 32-electrode data collection system for Electrical Impedance Tomography (EIT) will be presented. In this system, the demodulator is a multiplexed sample and hold (S&H) circuit followed by a voltage difference stage. This configuration provides high CMRR due to the low (almost DC) operating frequency of the signals the difference stage is required to process. PMID- 7790021 TI - Human alpha beta T-cell receptor CD4-CD8 T-cell clones are predominantly Th0 like. AB - The cytokine production profile, focusing on interleukin-4 (IL-4), interferon gamma (IFN-gamma) and interleukin-10 (IL-10) of human CD4+, CD8+ and CD4- CD8- alpha beta T cells cloned from the peripheral blood of healthy individuals was compared. Solid-phase anti-CD3 stimulation of CD4- CD8- alpha beta T cell clones from one individual revealed a significantly increased frequency of IL-4 producing clones (81%), compared to CD4+ T cells (24%) or CD8+ (28%). All five CD4- CD8- alpha beta T-cell clones from two other individuals also produced IL-4. Clones that produced IFN-gamma with undetectable IL-4 production, thus being of the 'classical' Th1 phenotype, were infrequent in CD4- CD8- alpha beta T-cell clones (19%) compared to CD4+ (71%), and CD8+ clones (72%) cloned in OKT3, and CD4+ cells cloned in phytohaemaglutinin A (77%). Unlike previously reported studies with gamma delta cells, the alpha beta CD4- CD8- T cells produced IL-10 at appreciable frequency (38%) in PHA generated clones. The supernatants from anti-CD3 stimulated CD4- CD8- alpha beta T-cell clones contained sufficient IL-4 to activate B cells, enhancing CD23 and surface immunoglobulin M (IgM) expression and co-stimulating B-cell proliferation. These findings suggest that the function of CD4- CD8- alpha beta T cells is distinct from that of most CD4+ or CD8+ T cells. PMID- 7790022 TI - Antigen-presenting cells in the female reproductive tract: influence of sex hormones on antigen presentation in the vagina. AB - We report here that the stage of the reproductive cycle and the administration of physiological amounts of oestradiol to ovariectomized rats influences antigen presentation by macrophage/dendritic cells in the vagina. Antigen presentation is elevated when oestradiol levels in blood are low, and reduced just prior to ovulation. Of those hormones tested, only oestradiol lowered vaginal antigen presentation. When progesterone was given along with oestradiol, the inhibitory effect of oestradiol on vaginal antigen presentation was reversed. These studies demonstrate that the vagina is an inductive site and that antigen presentation is under hormonal control. Our results suggest that immunization studies designed to enhance mucosal immunity in the female reproductive tract should take into account the stage of the reproductive cycle when antigen is deposited. PMID- 7790023 TI - The survival and turnover of mature and immature CD8 T cells. AB - The present investigation has examined the phenotype, survival and fate of immature and mature CD8 T cells. CD4- CD8+ 'single positive' thymocytes (a model for recent thymic emigrants) were Thy-1+ CD45RC- RT6- before transfer to normal euthymic recipients, but changed phenotype within 7-10 days to become Thy-1- CD45RC+ RT6(+)--the phenotype of mature resting CD8 T cells. Following transfer to athymic nude recipients CD8 T cells from thoracic duct lymph of allotype marked rats increased 12-17-fold during the first 2 months. Proliferation occurred in the complete absence of CD4 T cells and the donor CD8 T cells persisted [at 15-18% of peripheral blood lymphocytes (PBL)] for the life of the recipients. When combined with equal numbers of CD4 T cells, however, CD8 T cells occupied only 3-4% of PBL; in these animals CD4 T cells plateaued at 15-16% of PBL. The results suggested that CD8 T cells competed poorly with rapidly dividing CD4 T cells for limited space in a recirculating pool in which total T-cell numbers are homeostatically regulated. Although able to proliferate and self renew in athymic nude recipients, when transferred to normal euthymic animals donor-derived mature CD8 T cells declined in number with time; their half-life was estimated to be 34 days. Similar studies with purified CD4- CD8+ 'single positive' thymocytes gave a comparable half-life of 37 days. The results indicated that lifespan was not due to an ageing process among CD8 T cells, but was rather a reflection of cell turnover dependent on thymic output. PMID- 7790024 TI - Predominance of MHC class II-restricted CD4+ cytotoxic T cells against mouse hepatitis virus A59. AB - Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined viral proteins and the course of the infection is not yet clear. We have analysed the cytotoxic T lymphocyte (CTL) response in mouse hepatitis virus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restricted cytotoxicity in mice infected with MHV-A59. We found no evidence of activation of the classical CD8+ MHC class I-restricted CTL. The virus-specific CD4+ CTL derived from two different mouse strains having different MHC haplotypes recognized the same immunodominant epitope. This epitope, comprising the amino acid residues 329-343 of the viral S-glycoprotein, was recognized both at the polyclonal level and by virus-specific CTL clones. Transfer studies using a MHV-A59-specific CD4+ CTL clone showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4+ CTL play a pivotal role in the protection against MHV A59 infections. PMID- 7790025 TI - Superantigen-induced peripheral T-cell deletion: the effects of chemical modification of antigen-presenting cells, interleukin-4 and glucocorticoid hormones. AB - Experiments were performed to evaluate the role of antigen-presenting cells (APC) and the effect of interleukin-4 (IL-4) and glucocorticoid hormone (GCH) exposure on the in vitro deletion of CD4+ CD8- and CD8+ CD4- T cells by staphylococcal enterotoxin B (SEB). APC fixation with the chemical cross-linker 1-ethyl-3-(3 dimethyl-aminopropyl) carbodiimide (ECDI) inhibited their capacity to induce SEB specific deletion of mature T lymphocytes. Deletion was not influenced by treatment with anti-CD28 antibodies, which modulate T-cell activation. However, it was augmented by IL-4, known to counteract anti-CD3- and GCH-induced thymocyte apoptosis, and was inhibited by dexamethasone (DEX). These results indicate that metabolically active APC are required for deletion of antigen-specific mature T cells and suggest that IL-4 and GCH can modulate this phenomenon in vitro. PMID- 7790026 TI - Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis. AB - This study determined the potential capacity of interleukin-10 (IL-10), compared with IL-4, to control the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-1 receptor antagonist (IL-1ra) and the expression of major histocompatibility complex (MHC) class II antigens by monocytes/macrophages isolated from synovial fluid of patients with rheumatoid or other forms of chronic inflammatory arthritis. Mononuclear cells were isolated from synovial fluid and peripheral blood and incubated with or without lipopolysaccharide (LPS), and with or without IL-10 (100 U/ml, 10 ng/ml) or IL-4 (10 ng/ml) for 22 hr. TNF-alpha, IL-1 beta and IL-1ra levels were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants, and MHC class II expression was examined on the monocytes/macrophages by flow cytometry. IL-10, unlike IL-4, decreased TNF-alpha production by LPS-stimulated synovial fluid cells to the same extent as by LPS-stimulated peripheral blood cells from the same patients. IL-10 and IL-4 suppressed equally IL-1 beta production by the same cells. However, only IL-4 significantly increased IL-1ra production by synovial fluid mononuclear cells. Synovial fluid cells expressed increased levels of MHC class II antigen, and these levels were not as efficiently suppressed by IL-10 as they were for peripheral blood cells. Because IL-10 and IL-4 differentially regulate TNF-alpha and IL-1ra production by synovial fluid mononuclear cells, selective use of either IL-10 or IL-4 in the treatment of chronic inflammatory conditions will depend on whether TNF-alpha or IL-1, respectively, is established as primarily responsible for the maintenance of the chronic inflammatory condition. PMID- 7790028 TI - Production of TNF-alpha, IL-6 and TGF-beta, and expression of receptors for TNF alpha and IL-6, during murine Mycobacterium avium infection. AB - The Mycobacterium avium complex comprises intracellular bacteria associated with disseminated infection in patients with acquired immune deficiency syndrome (AIDS). Immune defects that lead to infection are unknown but cytokines appear to play an important role in the immunomodulation of host defence mechanisms. We evaluated the cytokine profiles seen temporally after murine M. avium infection. Spleen cells were obtained from M. avium-infected C57BL/6 mice and uninfected mice at weeks 1, 2, 3, 4 and 5. Cells were cultured in vitro and subsequently pulsed with killed M. avium. Supernatants were collected from the cultured splenic cells and the concentrations of interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis factor-alpha (TNF-alpha) were measured. TGF-beta 1 was detected at week 1, followed by IL-6 production at week 2. Elevated TNF-alpha levels were observed at week 3. The addition of polyclonal anti-TGF-beta 1 antibody to M. avium-infected peritoneal macrophages in the presence of splenic cell supernatants from weeks 1, 3 and 5 led to decreased bacterial counts compared to controls. Anti-IL-6 antibody did not have any effect on macrophage anti-mycobacterial activity. Concurrently, we observed decreased expression of TNF-alpha receptors on infected macrophages. We propose that the early elevated levels of TGF-beta 1, a known suppressor of macrophage function, in conjunction with down-regulation of TNF-alpha receptors may help explain the suboptimal macrophage response to TNF-alpha, leading to impaired anti mycobacterial activity. PMID- 7790029 TI - Permissive recognition of a mycobacterial T-cell epitope: localization of overlapping epitope core sequences recognized in association with multiple major histocompatibility complex class II I-A molecules. AB - Most T-cell epitopes are recognized in the context of a single or limited number of major histocompatibility complex (MHC) class II molecules. We have shown previously, however, that the immunodominant p61-80 epitope from the Mycobacterium tuberculosis 19,000 MW protein is recognized in a genetically permissive manner. In this study, permissive recognition of p61-80 was analysed in three murine MHC haplotypes (H-2b,d and k) with respect to: (i) T-cell-epitope core structure; (ii) I-A/I-E class II MHC restriction; and (iii) the identification of critical amino acid residues within the core region. Overlapping epitope core sequences composed of 6 to 8 amino acids were identified for each of the three H-2 haplotypes by T-cell epitope scanning (PEPSCAN) using peptide-specific T-cell lines. The epitope core sequences recognized by peptide and 19,000 MW protein-specific T cells were similar. In all three haplotypes, responses to p61-80 were restricted by class II MHC I-A molecules. To identify residues within the epitope core critically required for recognition, single substitution (alanine or leucine) analogue peptides were tested for their capacity to stimulate p61-80-specific T-cell hybridomas. A heterogeneous pattern of reactivity was observed, even among individual hybridomas derived from the same H-2 haplotype. Although every core residue could be defined as critical for at least one hybridoma, only one critical substitution (74Val-->Ala) was common to all hybridomas. The identification and structural analysis of genetically permissive epitopes of mycobacteria may be a useful strategy for the rational design of peptide-based vaccines for tuberculosis. PMID- 7790027 TI - DNA damage induced by tumour necrosis factor-alpha in L929 cells is mediated by mitochondrial oxygen radical formation. AB - Treatment of L929 cells with tumour necrosis factor-alpha (TNF-alpha) plus actinomycin D induced DNA damage (indicated by the appearance of a sub-G1 peak due to extracellular leakage of low molecular weight DNA following DNA fragmentation) before significant cell lysis occurred. The DNA damage occurred in parallel with a decrease of the intracellular total glutathione content and an increase of intracellular reactive oxygen intermediates (ROI), as indicated by increased dihydrorhodamine 123 oxidation. Because the inhibition of mitochondrial respiration suppressed the increase of dihydrorhodamine 123 oxidation and DNA damage as well as the decrease in the total glutathione content, it was suggested that increased mitochondrial formation of ROI was responsible for DNA damage after TNF treatment. Deferoxamine (a ferric iron chelator) and dithiothreitol (a sulfhydryl reagent) both prevented DNA damage and cell killing, indicate that hydroxyl radicals generated from O2- and H2O2 produced by the mitochondria in a process catalysed by iron contributed to DNA damage and that this pathway may be involved in TNF-alpha-induced cytotoxicity. An inhibitor of poly(ADP)-ribose polymerase (3-aminobenzamide), worsened DNA damage, but was protective against cell lysis, suggesting that DNA repair subsequent to injury was more important than DNA damage per se in development of TNF-alpha cytotoxicity. PMID- 7790030 TI - Development of grafted gld cells in athymic and euthymic recipients. AB - Mice homozygous for the gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutations display similar autoimmune and lymphoproliferative diseases. Both result from defective apoptosis, the targets of the lpr and gld mutations being the genes for, respectively, an apoptosis signalling receptor [the Fas antigen receptor (FasR)] and its counter-receptor [the Fas ligand (FasL)]. Though this definitely causes the development and accumulation of large numbers of unusual Thy-1+ B220+ cells in peripheral lymphoid organs, details on how this actually occurs are still lacking. Whether differentiation of gld T cells into Thy-1+ B220+ cells might depend on the environment was analysed by phenotyping the cells which expanded in four different immunodeficient environments (nubg, nulpr, scid and scidbg). Though all four types of congenic chimeras developed hyperglobulinaemia, autoimmunity and a lymphoproliferative disease, substantial differences were found for the athymic and euthymic chimeras. In the athymic gld chimeras, the lymphoproliferation concerned all cell subsets, whereas in the euthymic gld chimeras it was, as in gld mice, due to the accumulation of cells of the Thy-1+ B220+ subset. Thus, the gld T cells could proliferate without differentiating into the Thy-1+ B220+ subset, but this depended on the nature of the environment. Furthermore, emergence of a gld syndrome in these four environments would suggest that B cells and stromal cells do not express FasL, at least in levels sufficient to compensate for the deficiency of the grafted gld cells. PMID- 7790032 TI - Functional heterogeneity among CD4+ T-cell clones from blood and skin lesions of leprosy patients. Identification of T-cell clones distinct from Th0, Th1 and Th2. AB - In the present study we examined the functional properties of T-cell clones reactive with Mycobacterium leprae and other mycobacterial antigens. Clones isolated from the skin lesions and blood of leprosy patients across the spectrum were exclusively CD4+CD8- and expressed the alpha beta T-cell receptor. Substantial heterogeneity in the production of cytokines, in particular interleukin-4 (IL-4), was observed, although no striking correlation with clinical status was apparent. A variety of patterns of cytokine secretion distinct from those of T-helper type-1 (Th1) Th2 or Th0, as defined in murine studies, was evident. Most noteworthy was a large number of clones from skin which secreted neither IL-2 nor IL-4, but large amounts of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). Clones isolated from the blood of leprosy patients had a more restricted cytokine secretion profile, and appeared to resemble more closely previously described patterns, including those of high level production of IL-2 and/or IL-4. Virtually all clones, from either skin or blood, produced high levels of IFN-gamma, and thus many clones were IL-4 and IFN gamma co-producers. The pattern of cytokine production by skin-derived T-cell clones was significantly affected by the in vitro activation status of the cells. Cells enriched in activated blasts tended to produce more IL-4 than small resting cells. In addition, the production of IFN-gamma by skin T-cell clones after < or = 10 weeks of culture was strikingly distinct from that of these clones after 5 months of culture. IL-4 and IFN-gamma co-producing clones shifted to a Th2-like pattern with much less IFN-gamma secretion, whereas non-IL-4-producing clones secreted much higher levels of IFN-gamma after prolonged culture, and became much more Th1-like. However, there was still no correlation between clinical status and pattern of cytokines produced. These results imply that a high fraction of T cells exists in leprosy lesions that is distinct from or that has not yet fully matured into Th1 or Th2 cells. PMID- 7790033 TI - Antibody-induced modulation of CD26 surface expression. AB - The ability of different anti-CD26 monoclonal antibodies to modulate the expression of CD26 on human T lymphocytes was investigated. By means of a new non radioactive method using fluorescein isothiocyanate (FITC)-labelled and unlabelled anti-CD26 monoclonal antibodies and flow cytometry, we measured the internalization and re-expression of CD26 on freshly isolated resting human T lymphocytes. The modulation of CD26 surface expression takes place in primarily CD26+ as well as in CD26- T lymphocytes, indicating the presence of an intracellular CD26 pool. In fact, with two different anti-CD26 monoclonal antibodies (Ta1 and M5) intracellular CD26 was detected out of which newly expressed CD26 might have originated. This intracellular CD26 pool appears to be maintained by continuous translation of CD26 mRNA. PMID- 7790031 TI - Contact-dependent stimulation of monocytic cells and neutrophils by stimulated human T-cell clones. AB - By means of direct cell-cell contact, fixed, stimulated T lymphocytes trigger the production of interleukin-1 beta (IL-1 beta) and tumour necrosis factor by monocytes and prime polymorphonuclear leucocytes (PMN) for the respiratory burst induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP). In order to assess whether this activity is displayed by a particular subpopulation of T lymphocytes, 88 T-cell clones (TCC) were generated from healthy human peripheral blood. The clones were stimulated by Phaseolus vulgaris agglutinin (PHA) and phorbol 12-myristate acetate monocytic cell line THP-1. All fixed, stimulated TCC induced IL-1 beta production by THP-1 cells, although to varied degrees. The activity of TCC on THP-1 cells correlated with their activity on PMN (r2 = 0.84, P < 0.001), suggesting that this pro-inflammatory activity of TCC may similarly affect both types of infiltrating cells. The ability of TCC to modulate target cells did not correlate with either their phenotype (CD4 or CD8) or their cytokine production profile (interferon-gamma, IL-4 and IL-6), although it tended to correlate inversely with their capacity to produce IL-6 (P < 0.02). These observations suggest that a large proportion, if not all, of human peripheral blood T lymphocytes may potentially affect monocytes and PMN by direct cell-cell contact. This activity may be relevant to the maintenance of chronic inflammation. PMID- 7790034 TI - Characterization of intermediate T-cell receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts. AB - Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-alpha beta cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor beta-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice. PMID- 7790035 TI - The J alpha segment contributes to the affinity of V beta 6+ cells for vSAG-7 (Mls-1a) presented by I-A molecules. AB - Recognition of superantigens (SAG) by T cells is major histocompatibility complex (MHC) dependent but not MHC restricted. In the case of vSAG-7 (Mls-1a), encoded by the Mtv-7 provirus, I-E molecules play a dominant role in the vSAG-7-MHC-T cell receptor (TCR) interaction, the I-A molecule being less important. vSAG-7 is recognized predominantly by T cells bearing the V beta 6 element, which are deleted in Mtv-7+ mice; this deletion is nearly complete in mice expressing I-E molecules, but only partial in mice expressing exclusively the I-A molecules of permissive haplotypes. In view of these data, we hypothesized that vSAG-7 specific V beta 6+ T cells have a large spectrum of affinities for the MHC-vSAG-7 complex and that all of them, even those with a relatively low affinity, recognize the I-E-vSAG-7 complex, while only those with high affinity can recognize the I-A-vSAG-7 complex. Fourteen CD4 V beta 6+ vSAG-7-specific clones were studied and classified into three groups of avidity, depending on their interactions with different I-E- I-A(+)-vSAG-7 permissive haplotypes. Sequencing of the alpha and beta chains of their TCR suggested that the affinity for the vSAG-7 is influenced by the J alpha element. Four out of six low-affinity T-cell clones possessed the transcript for the J alpha 34 segment. Furthermore, five out of six low-affinity T-cell clones had the GGSN sequence in their CDR3 alpha, while the sixth low affinity clone had the conservative substituted SGGN sequence. These results strongly suggest that the expression of the J alpha 34 segment confers a very weak reactivity to T cells recognizing vSAG-7. PMID- 7790037 TI - Membrane cofactor protein (CD46) in seminal plasma is a prostasome-bound form with complement regulatory activity and measles virus neutralizing activity. AB - Human seminal plasma contains 0.55 microgram/ml of membrane cofactor protein (MCP; CD46) of 60,000 MW. By ultracentrifugation, gel filtration and immunoelectron microscope methods, we found that the MCP in seminal plasma was associated with prostasomes. The functional properties of the prostasome-bound MCP were assessed in comparison with a recombinant soluble form, gamma MCP1, which is composed of four short consensus repeats (SCR), type C of the serine/threonine-rich domain (STC), and unknown significance (UK). The MCP in seminal plasma, although demonstrably bound to prostasomes, behaved more like the soluble form of MCP. In the absence of detergent it, together with factor I, degraded the fluid-phase ligand, methylamine-treated C3 [C3(MA)], which is insensitive under no-detergent conditions to the membrane form of MCP and factor I. Moreover, C3dg fragment was generated as a final product instead of C3bi during the incubation, indicating that the prostasomal MCP and proteases may be responsible for the C3dg generation. The prostasomes neutralized measles virus (MV) infectivity, while gamma MCP1, for the most part, did not. These results, taken together with the CD59 concentration on the prostasomes, suggest that the prostasomes are potential immunomodulators for complement activation, providing the C3- and C9-step inhibitors. The present report also reinforces the idea that there are two different forms of MCP in semen. One is located in the inner acrosomal membrane of spermatozoa, which appears through acrosomal reaction and spermatoon-egg interaction. The other is a prostasome-bound form maintaining activities sufficient to regulate complement activation and, probably, MV infection. PMID- 7790038 TI - Requirement of CD4+ T cells and antigen-presenting cells for primary in vitro generation of CD8+ cytotoxic T cells against Ld-binding self-peptide p2Ca. AB - We investigated the cellular requirement for primary in vitro generation of cytotoxic T-lymphocytes (CTL) in BALB/c spleen cells against Ld-binding self peptide p2Ca. Depletion of CD4+ T-cells in vitro by pretreatment with anti-CD4 monoclonal antibody (mAb) and complement or in vivo by administration of anti-CD4 mAb abrogated generation of CTL. Depletion of adherent cells by passing spleen cells through a nylon wool (NW) column also abrogated generation of CTL. Addition of peritoneal exudate cells (PEC) to spleen cells passed through the NW column restored CTL generation. These findings indicate that both CD4+ T-cells and antigen-presenting cells (APC) were necessary for CTL generation. Treatment of PEC with paraformaldehyde (PFA), but not mitomycin-C (MMC) abrogated their ability to restore CTL generation when mixed with spleen cells from the NW column, suggesting that an endocytic pathway could be involved in presentation of p2Ca on APC. PMID- 7790039 TI - Modulation of mRNA expression and secretion of C1q in mouse macrophages by anti inflammatory drugs and cAMP: evidence for the partial involvement of a pathway that includes cyclooxygenase, prostaglandin E2 and adenylate cyclase. AB - Isolated BALB/c mouse thioglycollate-elicited (inflammatory) peritoneal macrophages release at least 10 times more C1q than do isolated resident peritoneal macrophages. Addition of non-steroidal anti-inflammatory drugs (NSAID) to thioglycollate-elicited macrophages in culture inhibited the release of C1q and reduced levels of C1q-specific mRNA. Contrastingly, the NSAID were found to enhance C1q-specific mRNA levels in resident macrophages, although no increase in C1q levels secreted was observed. This suggests that the response of macrophages to NSAID, with respect to C1q synthesis, reflects the developmental stage of the macrophage. The gold salt auranofin (AFN) was found to enhance markedly C1q synthesis at both transcriptional and secretory levels in thioglycollate-elicited macrophages whilst, conversely, AFN reduced mRNA levels in resident macrophages. This indicates that AFN and the NSAID may work via the same or similar biochemical pathway, but with opposing effects. The glucocorticoid hydrocortisone (HC) greatly enhanced C1q-specific mRNA levels in both thioglycollate-elicited and resident macrophages, although no parallel increases in C1q secreted were observed. The data on inhibition of C1q biosynthesis by NSAID in thioglycollate elicited macrophages are supported by the enhancement of C1q biosynthesis following addition of prostaglandin E2 (PGE2) or dibutyryl cyclic AMP (dBcAMP) to the cultures. From these experiments, it is concluded that C1q biosynthesis is controlled, at least in part, by a pathway involving cAMP. PMID- 7790040 TI - The anti-lipid A monoclonal antibody E5 binds to rough gram-negative bacteria, fixes C3, and facilitates binding of bacterial immune complexes to both erythrocytes and monocytes. AB - Treatment of patients with septic shock using monoclonal antibodies (mAbs) to endotoxin is still controversial. Clinical trials of E5, one of the mAbs directed against the lipid A moiety of lipopolysaccharide (LPS), are currently in progress. The mechanisms of action of this, and other antibodies under clinical evaluation, are, however, poorly understood. In this study we examined in vitro the ways in which E5 interacted with Gram-negative bacteria, complement, erythrocytes and monocytes. By fluorescence-activated cell sorter (FACS) analysis we showed direct, dose-dependent binding of E5 to Escherichia coli (E. coli) and Salmonella minnesota (S. minnesota). Antibody binding to S. minnesota was enhanced by treatment with the beta-lactam antibiotic amoxycillin, but not by treatment with the aminoglycoside gentamicin. Immune complexes formed between E5 and both species of Gram-negative bacteria activated both classical and alternative complement pathways, but only in the case of S. minnesota did this facilitate binding to erythrocyte CR1 and monocyte CR3. Bacterial C3b and iC3b fixation by E5 was quantified using specific mAbs. These observations suggest that E5 may enhance bacterial clearance in several ways: (1) by facilitating direct complement fixation; (2) by facilitating the binding of opsonized bacteria to cells of the mononuclear phagocyte system; (3) by enabling bacteria to bind to erythrocyte CR1 (CD35), allowing safe carriage in the circulation to the fixed macrophages of the liver and spleen; (4) by acting synergistically with beta lactam antibiotics. PMID- 7790042 TI - Characterization of local antibody responses to the gastrointestinal parasite Haemonchus contortus. AB - The ability to identify antigens associated with an infection has generally relied on the use of serum antibodies produced by infected or previously exposed individuals. A major drawback with the use of serum is that it does not necessarily reflect the local antibody response at mucosal tissue sites. This study describes an approach that allows the use of antibodies generated close to the infection site to detect the transient expression of stage-specific antigens during infection with the gastrointestinal parasite Haemonchus contortus. This was achieved by infecting immune sheep with H. contortus larvae and removing the abomasal lymph nodes draining the infection site shortly after the challenge infection. Antibody-secreting cell (ASC) probes were generated from these lymph nodes after short-term in vitro culture of cell suspensions, which allowed the accumulation of antibodies secreted by in vivo-induced ASC into the culture supernatant. Lymph node culture supernatants (= ASC probes) from immune sheep challenged 5 days previously were used to probe Western blots of third and fourth stage larval preparations, and revealed distinct reactivity to larval antigens. No antibody reactivity to larval antigen preparations was detected in sheep that were not challenged. The number of antigens identified using ASC probes was significantly restricted compared to either pre- or post-challenge sera. In contrast to the variability of the serum response, the specificity of ASC probes was highly repeatable between different sheep. ASC probes were also used to purify a H. contortus larval antigen by affinity chromatography, which allowed limited biochemical studies to be undertaken. The antigen(s) recognized by the ASC probes were shown to be expressed on the surface of the larvae. These studies illustrate the use of a novel means of studying the local antibody response close to a mucosal infection site in order to identify and isolate stage-specific antigens expressed during infection. PMID- 7790036 TI - Blocking measles virus infection with a recombinant soluble form of, or monoclonal antibodies against, membrane cofactor protein of complement (CD46). AB - Human membrane cofactor protein (MCP, CD46) functions as an inhibitor of the complement (C) cascade to protect host cells from C attack, and as a receptor for measles virus (MV). Normal human sera contains 10-60 ng/ml of naturally produced soluble forms of MCP, which is also a cofactor for the factor I-mediated inactivation of C3b. We produced monoclonal antibodies (mAb) against MCP and a recombinant soluble form of MCP similar to the natural soluble forms, and tested their ability to block MV infection. Vero cells and CHO cells expressing human MCP were the targets. Of the antibodies tested, M75 and M177, which blocked the C regulatory activity of MCP, efficiently blocked MV infection. More than 50 micrograms/ml of the soluble form moderately blocked MV infection of CHO cells expressing MCP, but barely blocked that of Vero cells. The two mAb and the soluble form also inhibited MV H protein-mediated green monkey erythrocyte rosette formation. A quantitative analysis suggested that 30 micrograms/ml of the soluble form functionally corresponded to 0.2 microgram/ml of M177 or M75. These data established that the C regulatory function and the MV receptor function of MCP were blocked simultaneously by the individual mAb, and that soluble forms of MCP could inhibit MV infection in cells expressing human MCP, although doses far higher than the natural concentration of soluble MCP were required. PMID- 7790043 TI - Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin. AB - We investigated serum tryptophan (Trp), neopterin (NPT) and immunosuppressive acidic protein (IAP), one of tumor-associated tumor marker, concentrations in 28 patients with gastrointestinal tumors representing cancer cachexia and 10 healthy controls. NPT comes from activated macrophages presumably activated by tumor sensitized T cells via gamma-interferon (IFN-gamma) excitation of the macrophages. We found that the NPT level was significantly higher than the control value. The negative correlation of NPT and Trp concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO), a Trp degradating enzyme, in cancer-burden patients. The activity of IDO can be induced by cytokines such as IFN-gamma, and therefore low Trp levels may result from endogenous IFN-gamma production due to immune activation against tumors. We also found a positive correlation between NPT and IAP levels, suggesting that host immune activation against tumors played a role in the immunosuppression of cancer-burden states, followed by cancer-cachexia. PMID- 7790041 TI - Characterization of a progesterone-binding, three-domain antibody fragment (VH/K) expressed in Escherichia coli. AB - The heavy chain variable region (VH) and the kappa light chain of the anti progesterone monoclonal antibody (mAb) DB3, have been expressed as a single-chain three-domain polypeptide, designated VH/K, and secreted into the periplasmic space of Escherichia coli (E. coli). The linker sequence was derived from the VH CH1 elbow region. The C kappa domain provides a sensitive detection tail for Western blotting and enzyme-linked immunosorbent assay (ELISA). Periplasmic extracts of transformed E. coli contained material that bound progesterone and related steroids with similar specificity and affinity to DB3, and displayed the DB3 idiotype and kappa chain epitopes. Reference to the crystal structure of DB3 suggests that all the characteristics of the combining site interaction with steroids are retained in the bacterially expressed material. Western blotting demonstrated material with a molecular weight equivalent to three domains after reduction, but six domains in the unreduced state, suggesting that the VH/K polypeptide is assembled in the periplasm as a disulphide-bridged dimer. The VH/K construct provides a novel route to expression of antibody combining sites in E. coli for antibody engineering. PMID- 7790044 TI - Plasma neopterin/C-reactive protein ratio as an adjunct to the assessment of infection and cancer cachexia. AB - Neopterin (NPT), a pteridine intermediate metabolite in the biopterine synthetic pathway, is synthesized and secreted by monocytes/macrophages upon stimulation, mainly by gamma-interferon produced by activated T cells. C-reactive protein (CRP) is one of the major acute-phase reactants and its release is thought to be mediated by interleukin-6. Plasma concentrations of NPT and CRP were synchronously analyzed in 25 determinations of 5 patients with severe infectious complications and 50 determinations of 10 cancer-burden patients representing cachexia. The mean value of NPT (pmol/ml) was 201.6 in the infection group and 16.5 in the cancer cachexia group. The mean value of CRP (mg/dl) was 12.5 in the infection group and 3.4 in the cancer cachexia group. The number of samples in which NPT alone exceeded the cut-off level were 0/25 (0%) in the infection group and 38/50 (76.0%) in the cancer cachexia group. The number of samples in which both NPT and CRP exceeded the cut-off level was 25/25 (100%) in the infection group and 12/50 (24.0%) in the cancer cachexia group. The mean ratio of NPT to CRP was 11.3 in the infection group and 30.7 in the cancer cachexia group, respectively. These results suggest that gamma-interferon could play the principal role in the pathogenesis of cancer cachexia and that interleukin-6 modified the disease status. Interleukin-6 would be the critical mediator of host responses in infectious complications. PMID- 7790045 TI - A simple method to selectively expand HIV-1 specific cytotoxic T lymphocytes in vitro. AB - Cytotoxic T lymphocytes (CTL) may play a critical role in controlling the progression of HIV-1 disease. Conventional assays for demonstration of CTL against HIV-1 have used either fresh PBMC or T cell lines and clones generated by non-specific stimulation. These methods are limited in their sensitivity since without specific secondary stimulation in vitro, epitopes recognized at low frequency may not be detected. Moreover, derivation of CTL clones is labor intensive and not practical for studying a large number of patients. We have developed a simple method to enrich HIV-1 specific CTL in vitro. Autologous antigen presenting cells (APC), either adherent macrophages or EBV transformed B lymphoblastoid cells, are infected with recombinant vaccinia virus encoding individual HIV-1 proteins and after overnight culture the vaccinia virus is inactivated by uv irradiation in the presence of psoralin. The infected APC are then cultured with patient's T cells and CTL activity determined 10-14 days later. We have used this method to stimulate patients' T cells obtained directly from PBMC and also after mitogenic stimulation. In both systems, the HIV-1 specific response could be enhanced up to five to ten fold. This enhancement is comparable to CTL selection by exposure to HIV-1 immunodominant peptide incubated APC. In some patients, viral-specific CTL could be detected after HIV-vaccinia selection even though the mitogen stimulated cultures had no demonstrable antiviral CTL activity. Selective expansion of CTL directed against multiple HIV 1 proteins (env, gag and RT) could be obtained from PBMC as well as from mitogen stimulated lines from individual patients. As these lines are predominantly CD8+ T cells by flow cytometric analysis and are free of vaccinia virus as ascertained by the lack of cytopathic effect in culture, in vitro vaccinia selection might also be useful to generate CTL lines for adoptive immunotherapy. PMID- 7790047 TI - The effect of molecular weight and gel preparation on humoral adjuvancy of silicone oils and silicone gels. AB - Silicone gels from commercial breast implants have been shown previously by our laboratory to be potent humoral adjuvants, while the low molecular size 20 centistoke (cs) silicone oil (M.W. 1900) possesses no measurable adjuvant properties. It became necessary to shear the silicone gel during our previous experiments in order to facilitate injection through a syringe and needle, it is conceivable that shearing may reduce the molecular weight of the silicone gel used. This investigation was undertaken to determine whether humoral adjuvancy of silicone oils is dependent on molecular weight and whether the method of shearing the silicone gel affects its adjuvancy. Four Dow Corning 360 Medical silicone oils (100 cs, M.W. approximately 5,000; 350 cs, M.W. approximately 10,000; 1000 cs, M.W. approximately 16,500 and 12,500 cs, M.W. approximately 60,000) and Dow Corning octamethylcyclotetrasiloxane (D4, M.W. 296) were tested for their humoral adjuvancy by immunizing 64 Sprague Dawley rats with 50 micrograms of bovine serum albumin (BSA) mixed with each oil. The rats were periodically bled and the sera were analyzed for anti-BSA antibodies by ELISA. In a separate experiment, three silicone gel preparations with reproducible characteristics were prepared by using a tissue homogenizer and varying the applied shear force. Each of these preparations was tested for its humoral adjuvancy as previously described for silicone oils. Rats immunized with BSA mixed with the highest molecular size silicone oil tested (M.W. approximately 60,000) showed a significant increase in anti-BSA antibodies as compared to the lower molecular size oils. The three silicone gel preparations showed no difference in their adjuvancy effect. Thus, the humoral adjuvancy of silicone oil appears to be dependent on molecular weight. Differential shearing of the silicone gel does not alter its humoral adjuvancy. PMID- 7790046 TI - Synergistic activation of serum amyloid A (SAA) by IL-6 and IL-1 in combination on human Hep 3B hepatoma cell line. Role of PGE2 and IL-1 receptor antagonist. AB - Serum amyloid A (SAA) protein is a major acute phase reactant in human and many other species. Infections and traumatic inflammation are characterized by a rapid increase of SAA; its concentration in the plasma may augment many-fold. Cytokines such as IL-1 and IL-6 are considered mediators of acute phase protein synthesis. The most accredited mechanism of action of IL-1 in inflammatory diseases is the stimulation of PGE2 release, which is highly dependent on the concentration of IL 1. In this study we found that human Hep 3B hepatoma cells treated with the combination of hrIL-6 (10ng/ml) plus hrIL-1 (1ng/ml) produced an augmentation in steady-state levels of SAA mRNA (87%) compared to hrIL-6 (10ng/ml) plus PGE2 (5 microM), which induced an increase of only 33%, compared to IL-6 alone, while cells treated with hrIL-6 plus PGE2 (0.5 microM) had a similar effect as hrIL-6 did alone. Moreover, the addition of exogenous PGE2 (5 microM) to the cell cultures produced no significant increase in concentration of SAA mRNA compared to the control. In addition, according to the data obtained by the blot analysis we also found, by ELISA method, that hrIL-6 acts in synergism with hrIL-1 on SAA protein secretion in human Hep 3B hepatoma cell cultures after 48 h incubation. In fact, the cell cultures treated with hrIL-6 plus hrIL-1 caused a higher release approximately 1.5-4-fold of SAA protein than the cells treated with IL-6 plus PGE2 5 microM or IL-1 + PGE2 5 microM, respectively. The synergistic effect of hrIL-6 plus hrIL-1 beta was inhibited by hrIL-1 receptor antagonist (hrIL-1ra) 50 micrograms/ml, a protein which specifically binds to the IL-1 receptor and is structurally similar to IL-1 beta but with no IL-1-like activity; while indomethacin (5 microM) was ineffective. These results strongly suggest that the synergism between hrIL-6 plus hrIL-1 on the transcription and the protein release of SAA release is not due to a PGE2-dependent process in human Hep 3B hepatoma cells. This finding highlights a specific biological effect of IL-1 not in relation to PGE2, suggesting a specific mechanism of action for IL-1 in regulating acute phase protein synthesis. PMID- 7790048 TI - Active immunity to Pneumocystis carinii reinfection in T-cell-depleted mice. AB - Immunocompetent C.B-17 mice were immunized against Pneumocystis carinii by several intratracheal inoculations with infective P. carinii. These mice and another group of C.B-17 mice naive to P. carinii were then depleted of CD4+ cells by treatment with both anti-CD4 and anti-Thy1 monoclonal antibodies. Both groups of mice were then challenged with an infective inoculum containing 10(7) P. carinii organisms by intratracheal instillation. The mean log10 counts of P. carinii nuclei in the lungs of the nonimmune mice were 4.98, 5.89, and 6.77 when they were killed at 4, 10, and 19 days, respectively, after challenge. The P. carinii counts in the lungs of the immune mice were significantly lower at each time point and below detectable levels at 10 and 19 days. Analysis of P. carinii DNA by PCR revealed no detectable P. carinii in the lungs of the immunized mice at either 10 or 19 days, whereas all of the nonimmunized mice contained P. carinii DNA at all time points. The sera of immune but not nonimmune mice contained P. carinii-specific immunoglobulin G. These results indicate that immunization of an immunocompetent host against P. carinii can protect against P. carinii pneumonia even after the host is depleted of CD4+ cells. In addition, the results are consistent with the possibility that antibodies were responsible for the observed protection against P. carinii. PMID- 7790049 TI - Intracellular processing of liposome-encapsulated antigens by macrophages depends upon the antigen. AB - Two proteins, a recombinant malaria protein (R32NS1) and conalbumin, were encapsulated in separate liposomes. The mechanisms of presentation of unencapsulated and liposome-encapsulated R32NS1 and conalbumin to antigen specific T-cell clones were investigated in in vitro antigen presentation assays using murine bone marrow-derived macrophages (BMs) as antigen-presenting cells. A much lower concentration of liposomal antigen than of unencapsulated antigen was required for T-cell proliferation. Liposome-encapsulated conalbumin required intracellular processing by BMs for antigen-specific T-cell proliferation, as determined by inhibition with chloroquine, NH4Cl, leupeptin, brefeldin A, monensin, antimycin A, NaF, and cycloheximide and by treatment of BMs with glutaraldehyde. Liposome-encapsulated conalbumin therefore follows the classical intracellular antigen processing pathway described for protein antigens. Similarly, unencapsulated conalbumin also required intracellular processing for presentation to antigen-specific T cells. In contrast, both unencapsulated R32NS1 and liposome-encapsulated R32NS1 were presented to T cells by BMs without undergoing internalization and intracellular processing. These results suggest that the antigen itself is the major element that determines whether a requirement exists for intracellular processing of liposomal antigens by macrophages. PMID- 7790050 TI - Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis. AB - The etiology of recurrent vulvovaginal candidiasis in otherwise healthy women of child-bearing age remains an enigma. To date, results from both clinical studies and a murine model of vaginal candidiasis indicate that Candida vaginitis can occur in the presence of Candida-specific Th1-type cell-mediated immunity expressed in the peripheral circulation. The present study was designed to determine the role of circulating CD4 and CD8 cells in primary and secondary vaginal infections with Candida albicans. Vaginal fungal burden, Candida-specific delayed-type hypersensitivity (DTH), and lymph node cell Th1/Th2 cytokine production were monitored in CD4 and/or CD8 cell-depleted mice during persistent primary vaginal infections and secondary vaginal infections against which partial protection was observed. Treatment of mice with anti-CD4 or anti-CD8 antibodies resulted in 90% or greater depletion of the respective cell populations. Mice depleted of CD4 cells had significantly reduced Candida-specific DTH and lymph node cell Th1-type cytokine production during a primary vaginal infection, as well as reduced anamnestic DTH during a secondary vaginal infection. In contrast, mice depleted of CD8 cells showed only reduced gamma interferon production during a primary infection; no alterations in DTH were observed. Despite reductions in DTH and cytokine production, however, CD4 and/or CD8 cell depletion had no effect on vaginal C. albicans burden in mice after a primary or secondary vaginal inoculation. Taken together, these results suggest that while circulating CD4 and CD8 cells contribute to systemic Candida-specific cell-mediated immunity in vaginally infected mice, neither CD4 nor CD8 circulating T cells appear to provide significant host defenses against C. albicans at the vaginal mucosa. PMID- 7790052 TI - Purification and characterization of a Chinese hamster ovary cell elongation factor of Vibrio hollisae. AB - The halophilic bacterium Vibrio hollisae, isolated from patients with diarrhea, produces an extracellular toxin which elongates Chinese hamster ovary (CHO) cells. We purified this toxin to homogeneity by sequential ammonium sulfate precipitation, gel filtration with Sephacryl S-200, hydrophobic interaction chromatography with phenyl-Sepharose CL-4B, ion-exchange chromatography with DEAE Sephadex A-50, and affinity chromatography. The toxin is heat labile and sensitive to proteases, with an isoelectric point of about 6.5 and molecular weights of about 83,000 and 80,000, as estimated by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively. The toxin did not react with immunoaffinity-purified antibodies to cholera toxin in a plate enzyme-linked immunosorbent assay and in a Western blot, and its activity could not be neutralized by anti-cholrea toxin serum. Mixed gangliosides and gangliosides GM1, GD1a, GD1b, Gq1b, GT1b, GD2, GD3, GM2, and GM3 failed to block its activity. Elongation of CHO cells induced by the toxin was not accompanied by an increase in the levels of cyclic AMP. The toxin induced intestinal fluid accumulation in suckling mice. These results and the lack of homology between V. hollisae DNA and DNA coding for cholera toxin or the heat-labile toxin of Escherichia coli suggest that the V. hollisae toxin is structurally and functionally different from other CHO cell-elongating toxins. PMID- 7790051 TI - Clonal relationships among bloodstream isolates of Escherichia coli. AB - The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at Boston, Mass., Long Beach, Calif., and Nairobi, Kenya, were determined by multilocus enzyme electrophoresis (MLEE), analysis of polymorphisms associated with the ribosomal operon (ribotyping), and serotyping. MLEE based on 20 enzymes resolved 101 electrophoretic types (ETs), forming five clusters; ribotyping resolved 56 distinct patterns concordant with the analysis by MLEE. The isolates at each study site formed a genetically diverse group and demonstrated similar clonal structures, with the same small subset of lineages accounting for the majority of isolates at each site. Moreover, two ribotypes accounted for approximately 30% of the isolates at each study site. One cluster contained the majority (65%) of isolates and, by direct comparison of the ETs and ribotypes of individual isolates, was genetically indistinguishable from the largest cluster for each of two other collections of E. coli causing pyelonephritis and neonatal meningitis (R. K. Selander, T. K. Korhonen, V. Vaisanen-Rhen, P. H. Williams, P. E. Pattison, and D. A. Caugent, Infect. Immun. 52:213-222, 1986; M. Arthur, C. E. Johnson, R. H. Rubin, R. D. Arbeit, C. Campanelli, C. Kim, S. Steinbach, M. Agarwal, R. Wilkinson, and R. Goldstein, Infect. Immun. 57:303-313, 1989), thus defining a virulent set of lineages. The isolates within these virulent lineages typically carried DNA homologous to the adhesin operon pap or sfa and the hemolysin operon hly and expressed O1, O2, O4, O6, O18, O25, or O75 antigens. DNA homologous to pap was distributed among isolates of each major cluster, whereas hly was restricted to isolates of two clusters, typically detected in pap-positive strains, and sfa was restricted to isolates of one cluster, typically detected in pap- and hly-positive strains. The occurrence of pap-positive isolates in the same geographically and genetically divergent lineages suggests that this operon was acquired early in the radiation of E. coli, while hly and sfa were acquired subsequently, most likely by pap positive and pap- and hly-positive precursors, respectively. PMID- 7790054 TI - Role of lipopolysaccharide (LPS), interleukin-1, interleukin-6, tumor necrosis factor, and dexamethasone in regulation of LPS-binding protein expression in normal hepatocytes and hepatocytes from LPS-treated rats. AB - Lipopolysaccharide (LPS)-binding protein (LBP) has been reported to be an acute phase protein. LBP binds to LPS with a high affinity; LPS-LBP complexes then interact with the receptor CD14, resulting in increased expression of LPS inducible genes. Hepatocytes represent a major source of LBP, but little is known about the regulation of rodent hepatocyte LBP synthesis. In these studies, undertaken to characterize hepatocyte LBP expression, we show that greater-than 20-fold increases in LBP mRNA levels in hepatocytes occurred following injection of LPS or turpentine in rats. In primary cultures of rat hepatocytes, the addition of interleukin-6 (IL-6) and LPS led to 4.5- and 3.2-fold stimulation in LBP mRNA levels, respectively. The induction of LBP by IL-6 or LPS was attenuated by dexamethasone. In contrast to IL-6 and LPS, in the presence of 10(-6) M dexamethasone, IL-1 and tumor necrosis factor (TNF) led to maximal LBP mRNA induction levels, 4.7- and 3.8-fold, respectively, suggesting that IL-6 and LPS stimulate LBP expression by mechanisms different from those of IL-1 and TNF. Similar induction levels of LBP mRNA were seen in rat H35 hepatoma cells for all four stimuli, and dexamethasone inhibited these responses. Dexamethasone alone increased the spontaneous induction in primary hepatocytes at early time points but suppressed induction at later time points. Furthermore, hepatocytes from rats treated with LPS in vivo exhibited a > 10-fold increase in mRNA expression in response to LPS and enhanced responses to TNF and IL-1. As with the normal hepatocytes, dexamethasone inhibited the LPS-dependent induction in the LPS treated rat hepatocytes. These data suggest that LBP synthesis by hepatocytes is under the control of LPS, IL-1, TNF, IL-6, and glucocorticoids and that the LPS treatment primes hepatocytes for subsequent responses to LPS, TNF, and IL-1 for LBP synthesis. PMID- 7790053 TI - Membrane topology of Borrelia burgdorferi and Treponema pallidum lipoproteins. AB - A critical issue regarding the molecular architectures of Treponema pallidum and Borrelia burgdorferi, the agents of venereal syphilis and Lyme disease, respectively, concerns the membrane topologies of their major lipoprotein immunogens. A related question is whether these lipid-modified membrane proteins form intramembranous particles during freeze fracture electron microscopy. To address these issues, native borrelial and treponemal lipoproteins were reconstituted into liposomes of diverse composition. The importance of the covalently associated lipids for membrane association of lipoproteins was revealed by the observation that nonlipidated recombinant forms of both B. burgdorferi OspA and the T. pallidum 47-kDa immunogen (Tpp47) showed very weak or no binding to model bilayer vesicles. In contrast to control liposomes reconstituted with bacteriorhodopsin or bovine rhodopsin, two well-characterized transmembrane proteins, none of the lipoprotein-liposomes contained particles when examined by freeze fracture electron microscopy. To extend these findings to prokaryotic lipoproteins with relatively amphiphilic polypeptides, similar experiments were conducted with a recombinant nonlipidated form of Escherichia coli TraT, a lipoprotein which has putative transmembrane domains. The nonlipidated TraT oligomers bound vesicles derived from E. coli lipids but, surprisingly, did not form particles in the freeze-fractured liposomes. These findings support (i) a proposed topology of spirochetal lipoproteins in which the polypeptide is extrinsic to the membrane surface and (ii) the contention that particles visualized in freeze-fractured spirochetal membranes represent poorly characterized transmembrane proteins. PMID- 7790055 TI - Salmonella enteritidis colonization of the reproductive tract and forming and freshly laid eggs of chickens. AB - Salmonella enteritidis colonizes the tissues of the chicken ovary and oviduct, presumably contaminating eggs and thereby contributing to human outbreaks of salmonellosis. In this study, commercial adult laying hens were given an oral inoculation of 10(8) S. enteritidis organisms. Tissues from various organs, the intestines, and the reproductive tract, including freshly laid eggs, were collected daily for up to 40 days postinoculation (p.i.). Within 2 days p.i. S. enteritidis was detected by culture in pools of the spleen, liver, heart, and gallbladder tissues, in intestinal tissues of all infected birds, and in various sections of the ovary and oviduct. Detection of organisms by immunohistochemical staining was rare for most tissues in spite of their culture-positive status, suggesting a low level of tissue colonization. However, S. enteritidis could be detected by immunohistochemical staining in oviduct tissues associated with four forming eggs, indicating the possibility of a heavier colonization in the egg during its development. In two subsequent experiments, forming eggs taken from the oviduct with their associated tissue, were found to be culture positive for S. enteritidis at a rate of 27.1 and 31.4%, while freshly laid eggs in these experiments were culture positive at the rate of 0 and 0.6%. These observations suggest that while forming eggs are significantly colonized in the reproductive tract, factors within the eggs may control the pathogen before the eggs are laid. The data show that prior to egg deposition, forming eggs are subject to descending infections from colonized ovarian tissue, ascending infections from colonized vaginal and cloacal tissues, and lateral infections from colonized upper oviduct tissues. The data are consistent with an ascending infection of freshly laid eggs from the cloaca, as the incidence of positive eggs in experiments 1 and 3 coincided with heavily contaminated cloacal tissues (50.7 and 80%, respectively), while no positive eggs were detected in experiment 2 when cloacal colonization was low (8.3%). The data do not support the possibility of egg invasion by bacterial translocation from the peritoneal cavity. PMID- 7790056 TI - Comparative toxicity and virulence of Escherichia coli clones expressing variant and chimeric Shiga-like toxin type II operons. AB - Shiga-like toxin (SLT)-producing strains of Escherichia coli are known to cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome in humans. The SLTs, particularly those related to type II (SLT-II), are a diverse family of toxins which may have differing in vitro or in vivo properties. To examine the impact of naturally occurring SLT-II sequence variation on the capacity of a given E. coli strain to cause disease, operons encoding four different SLT-II-related toxins, designated SLT-II/O111, SLT-II/OX3a, SLT-II/OX3b, and SLT-II/O48, were cloned in the same orientation in pBluescript. French pressure cell lysates of E. coli DH5 alpha derivatives carrying these plasmids differed markedly in cytotoxicity for Vero cells, with 50% cytotoxic doses ranging from 20 to 328,000/ml. The strains also differed in oral virulence for streptomycin-treated mice, as judged by survival rate and/or median survival time, but virulence did not necessarily correlate with in vitro cytotoxicity. The SLT-II type associated with the lowest oral virulence was SLT-II/O111. Both the overall survival rate and the median survival time of mice challenged with clones producing this toxin were significantly greater than that for mice challenged with a clone producing the closely related SLT-II/OX3a. Experiments with clones carrying chimeric O111/OX3a SLT-II operons indicated that the reduced virulence was associated with an Arg 176-->Gly substitution in the mature A subunit. Clones producing SLT-II/O48 and SLT-II/OX3b had similarly high cytotoxicities for Vero cells, but the latter was more virulent when fed to streptomycin-treated mice, as judged by median survival time. Experiments with clones carrying chimeric O48/OX3b SLT-II operons indicated that the increased virulence was a function of the A subunit of SLT-II/OX3b, which differs from the A subunit of SLT-II/O48 by only two amino acids (Met-4- >Thr and Gly-102-->Asp, respectively). These findings raise the possibility that naturally occurring SLT-II sequence variations may impact directly on the capacity of a given SLT-producing E. coli strain to cause disease. PMID- 7790057 TI - Characterization of a Tn4351-generated hemin uptake mutant of Porphyromonas gingivalis: evidence for the coordinate regulation of virulence factors by hemin. AB - The ability of Porphyromonas gingivalis to acquire iron in the iron-limited environment of the host is crucial to the colonization of this organism. We report here on the isolation and characterization of a transpositional insertion mutant of P. gingivalis A7436 (designated MSM-3) which is defective in the utilization and transport of hemin. P. gingivalis MSM-3 was selected on the basis of its nonpigmented phenotype on anaerobic blood agar following mutagenesis with the Bacteroides fragilis transposon Tn4351. P. gingivalis MSM-3 grew poorly when supplied with hemin as a sole source of iron; however, growth was observed with hemoglobin or inorganic iron. P. gingivalis MSM-3 grown in either hemin-replete or hemin-depleted conditions bound and transported less [14C]hemin or [59Fe]hemin than did the parent strain. At 4 h, P. gingivalis MSM-3 grown in hemin-replete conditions transported only 10,000 pmol of hemin per mg of protein, or 14% of the amount transported by P. gingivalis A7436. Unlike P. gingivalis A7436, hemin binding and transport by P. gingivalis MSM-3 were not tightly regulated by hemin or iron. Examination of P. gingivalis MSM-3 cultures by electron microscopy revealed an overproduction of membrane vesicles, and determination of the dry weight of purified vesicles indicated that P. gingivalis MSM-3 produced twice as much membrane vesicles as did strain A7436. Extracellular vesicles isolated from P. gingivalis MSM-3 also were found to express increased hemolytic and trypsin like protease activities compared with the parent strain. When inoculated into subcutaneous chambers implanted in mice, P. gingivalis MSM-3 was highly infectious and more invasive than the parent strain, as indicated by secondary lesion formation and death. Taken together, these results indicate that the decreased transport of hemin by P. gingivalis MSM-3 results in the increased expression of several virulence factors which may be coordinately regulated by hemin. PMID- 7790058 TI - Cellular immunity to the P6 outer membrane protein of nontypeable Haemophilus influenzae. AB - Cellular immunity to nontypeable Haemophilus influenzae in a population of 10 healthy, immune adults was determined by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. P6 (200 microliters/ml) induced lymphocyte blast transformation that peaked on day 10 of incubation. The peak induction of antibody-secreting cells occurred on day 8 of incubation. In comparison with the response to tetanus toxoid stimulation, the peak lymphocyte blast transformation response to P6 was reduced (mean counts per minute +/- standard error of the mean [SEM], 3,457 +/- 503 versus 9,414 +/- 1,464; P = 0.0051) and delayed (mean days +/- SEM, 10.3 +/- 0.4 versus 8.4 +/- 0.5; P = 0.0169); however, P6 was a better stimulus of antibody secretion from lymphocytes, particularly antibody of the immunoglobulin M (IgM) class (mean peak numbers of antibody-secreting cells per 10(5) peripheral blood mononuclear cells +/- SEM: IgG, 85 +/- 29 versus 42 +/- 16 [P = 0.0469]; IgM, 81 +/- 20 versus 25 +/- 7 [P = 0.0125]; IgA, 24 +/- 8 versus 16 +/- 6 [P = 0.0526]). Thus, lymphocytes from immune individuals recognize P6 of nontypeable H. influenzae as an immunogen. These data provide a basis for future studies with otitis-prone children who fail to develop a normal antibody response to P6 antigen (N. Yamanaka and H. Faden, J. Pediatr. 122:212-218, 1993). PMID- 7790059 TI - Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. AB - Several strains of Borrelia burgdorferi and Borrelia hermsii can bind human Lys plasminogen specifically. Affinity blots using 125I-labeled plasminogen showed that numerous polypeptides of all the strains and species tested could bind via lysine residues to the plasminogen molecule since binding could be completely inhibited by the lysine analog epsilon-aminocaproic acid. Binding analysis using 125I-labeled plasminogen on live intact organisms showed that the organisms possess two binding sites for plasminogen: a high-affinity site with a Kd of 24 +/- 12 pM and 106 +/- 14 binding sites per spirochete and a low-affinity site with a Kd of 20 +/- 4 nM and 2,683 +/- 36 binding sites per spirochete. Indirect immunofluorescence and confocal microscopy showed a generalized but punctate pattern of plasminogen binding to the spirochete surface. Exogenously provided urokinase-type plasminogen activator converted B. burgdorferi surface-bound plasminogen to enzymatically active plasmin as demonstrated by the breakdown of the chromogenic plasmin substrate S2251. Plasmin-coated organisms showed an enhanced ability to penetrate endothelial cell monolayers grown on connective tissue substrates compared to untreated controls (P < 0.001). This functional assay demonstrated that enzymatically active plasmin on the surface of spirochetes can lead to greater invasion of tissues. PMID- 7790060 TI - Binding of Haemophilus influenzae to purified mucins from the human respiratory tract. AB - Mucins are high-molecular-weight glycoproteins and major constituents of the mucus layer which covers the airway surface. We have studied the interactions between bacteria, mucins, and epithelial cells from the human respiratory tract. Nontypeable strains of Haemophilus influenzae were found to bind to purified airway mucins in suspension and on solid phase. Mucins in suspension inhibited the attachment of these strains to nasopharyngeal epithelial cells, while mucin coating of the cells enhanced their binding. In contrast, strains of Streptococcus pneumoniae and encapsulated and other nontypeable H. influenzae strains failed to interact with mucins. These H. influenzae strains used other strategies for adherence to epithelial cells. The type b strain 770235 attached via fimbriae but also expressed a subcapsular adhesin that was detected in a capsule- and fimbria-defective mutant. Mucin pretreatment of these bacteria did not inhibit adherence, but mucin pretreatment of epithelial cells inhibited adherence, probably by shielding of the receptors for these adhesins. Non-mucin binding nontypeable and encapsulated H. influenzae strains would, therefore, adhere only after disruption of the mucus layer and exposure of cellular receptors. Differences in tissue toxicity and invasiveness among H. influenzae strains may also be influenced by the mucin interactions of the strains. PMID- 7790061 TI - Peptide permeases from Streptococcus pneumoniae affect adherence to eucaryotic cells. AB - To gain access to tissues within the human host, Streptococcus pneumoniae initially colonizes the nasopharynx and then interacts with glycoconjugates on the surfaces of target cells at various sites of infection. Although pneumococcal adhesins are currently unknown, exported proteins on the bacterial surface are potential candidates. To identify bacterial elements involved in this process, mutants of S. pneumoniae with defects in exported proteins were screened for the inability to adhere to cells representative of three in vivo niches: (i) agglutination of bovine erythrocytes, which reflects adherence to cells which reside in the nasopharynx; (ii) human type II pneumocytes (lung cells [LC]), representing the alveolar site of infection; and (iii) human vascular endothelial cells (EC), representing the endovascular site. The capacity of the mutants to adhere during the course of pneumococcal disease was also assessed by using cytokine-activated LC and EC. All of the 30 mutants analyzed produced hemagglutination values comparable with those of the parent strain. Four independent mutants demonstrated a greater than 50% decrease in adherence to both LC and EC. Sequence analysis of the altered alleles from these strains showed that mutations had occurred in two previously identified loci, plpA and ami, which belong to the family of genes encoding protein-dependent peptide permeases. Mutations in the ami locus resulted in an inability to recognize the GalNAc beta 1-4Gal glycoconjugate receptor present on resting LC and EC, whereas mutations in plpA resulted in a failure to recognize a GalNAc beta 1-3Gal glycoconjugate receptor also present on resting cells. Mutations in neither allele affected recognition of GlcNAc receptors present on cytokine-activated LC and EC. These results suggest that peptide permeases modulate pneumococcal adherence to epithelial and endothelial cells either by acting directly as adhesins or by modulating the expression of adhesins on the pneumococcal surface during the initial stages of colonization of the lung or the vascular endothelium. PMID- 7790062 TI - Cloning and genetic characterization of the flagellum subunit gene (flaA) of Legionella pneumophila serogroup 1. AB - The gene flaA, encoding the flagellum subunit protein of Legionella pneumophila serogroup 1, has been isolated from an expression library of L. pneumophila isolate Corby in Escherichia coli K-12 by using an antiflagellin specific polyclonal antiserum. DNA sequence analysis of the flaA gene revealed the presence of a 1,428-bp open reading frame encoding a protein of 475 amino acids with an apparent molecular mass of 48 kDa that is expressed independently of an E. coli vector promoter. Peptide sequencing of the N terminus of the isolated flagellum subunit protein confirmed that this open reading frame encodes the flagellin. By comparing the FlaA amino acid sequence with those of flagellins of various other bacteria, high degrees of homology in the N-terminal and C-terminal amino acids could be observed. The flaA-specific mRNA was determined to be 1.6 kb in size, the expected size of a monocistronic mRNA. Temperature-dependent expression of flagellin was found to be regulated at the transcriptional level. Sequence analysis and primer extension experiments indicated that the transcription of the gene flaA is directed by a sigma 28-like RpoF-FliA factor. By using fliA and fliA+ E. coli K-12 mutants, it was shown that flaA expression in E. coli required the sigma 28 factor. A flaA-specific DNA probe hybridizes with genomic DNA isolated from L. pneumophila and with most of the genomic DNAs from non-L. pneumophila Legionella strains. Two L. pneumophila strains and isolates of Legionella bozemanii and Legionella feeleii (serogroup 1) carry flaA specific sequences but were not able to produce flagella. PMID- 7790063 TI - Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4 epimerase mutant of Neisseria meningitidis NMB. AB - Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3 deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure. PMID- 7790064 TI - Expression, purification, and characterization of a novel G protein, SGP, from Streptococcus mutans. AB - The sgp gene of Streptococcus mutans was recently detected immediately downstream from the dgk gene within the same operon. In this study, the sgp gene was subcloned into the pMAL-c2 vector and SGP (S. mutans G protein) was overexpressed in Escherichia coli as a fusion protein with the maltose-binding protein at a level of 40% of total cellular protein. One-step amylose affinity chromatography purification of this fusion protein yielded a product of approximately 95% purity. SGP was purified from this fusion protein following cleavage with protease factor Xa and DEAE-Sephacel chromatography. In nucleotide binding assays, recombinant SGP showed specific binding for GTP and GDP, but not ATP, CTP, and UTP, and also catalyzed efficient hydrolysis of GTP to GDP. Kinetic studies revealed that the SGP Km value for GTP in this reaction was approximately 5.9 microM. Mg2+ also served as a cofactor of SGP in this reaction. In vivo subcellular localization by immunogold labelling demonstrated that SGP was associated with both membrane and cytoplasmic fractions. SGP not only had structural similarities with other G proteins but also proved to have high-level intrinsic GTPase activity. Therefore, SGP appears to be a new member of the G protein superfamily and may participate in transmembrane signaling in the responses of S. mutans cells to environmental stimuli. PMID- 7790065 TI - Clonal diversity of the taxon Porphyromonas gingivalis assessed by random amplified polymorphic DNA fingerprinting. AB - A total of 97 strains of the periopathogen Porphyromonas gingivalis were collected. This collection included laboratory strains and clinical isolates of human origin with diverse clinical and geographical origins. Biological diversity was further increased by including 32 strains isolated from the oral cavities of nine different animal species. Genomic fingerprints of the 129 strains were generated as random amplified polymorphic DNAs (RAPDs) by the technique of PCR amplification with a single primer of arbitrary sequence. Four nonameric oligonucleotides were used as single primers, and the banding patterns of the DNA products separated on agarose gels were compared after ethidium ethidium bromide staining. Distance coeffients based on the positions of the major DNA fragments were calculated, and dendrograms were generated. We identified 102 clonal types (CTs) that could be assembled into three main groups by cluster analysis by the unweighted pair group method with mathematic averages. Group I (n = 79 CTs) included all 97 human strains and 6 monkey isolates. The strains in group II (n = 22 CTs) and III (n = 1 CT) were strongly differentiated from those in group I and included only strains of animal origin; they likely represent two cryptic species within the present P. gingivalis taxon. We observed that strains from Old World monkeys clustered together with the human genotype, whereas strains from New World monkeys clustered with the animal genotype. Our results with human strains also indicated that (i) the population structure is basically clonal, (ii) no dominant or widespread CT could be observed, and (iii) no relationship could be established between specific clusters of CTs and the periodontal status of the host. Our results corroborate previous findings by B. G. Loos, D. W. Dyer, T. S. Whittam, and R. K. Selander (Infect. Immun. 61:204-212, 1993) and suggest that P. gingivalis should be considered a commensal of the oral cavity acting as an opportunistic pathogen. Our results are not consistent with the hypothesis that only a few virulent clones of P. gingivalis are associated with disease. PMID- 7790066 TI - Suppressive effect of interleukin-4 neutralization differs for granulomas around Schistosoma mansoni eggs injected into mice compared with those around eggs laid in infected mice. AB - The principal pathological manifestation of murine Schistosoma mansoni infection is the egg-induced granuloma. Synchronous pulmonary granulomas forming around intravenously injected schistosome eggs are widely used to study the immunopathology of schistosomiasis. A number of anticytokine antibody treatments have a remarkable effect in modulating granulomas in this model but little effect on the size of hepatic granulomas around laid eggs during experimental infection. To examine this discrepancy, we examined the effects of anticytokine antibodies on liver and lung granulomas around injected eggs and around eggs laid during infection in both locations. Anti-interleukin-4 (IL-4) treatment greatly reduced the volume of granulomas around eggs injected into the liver via the portal vein and around eggs injected into the lung via the tail vein. On the contrary, granulomas around eggs laid by worms in either the liver or the lung during the course of infection were not significantly decreased in size by anti-IL-4 treatment. Thus, site is not important for the disparate effects of anti-IL-4 in granuloma formation around injected versus laid eggs. This effect is seen in naive and sensitized animals and is most probably due to differences in the quality of injected eggs versus those laid in situ by the worms. PMID- 7790067 TI - In vitro and in vivo characterization of an ail mutant of Yersinia enterocolitica. AB - Ail is a 17-kDa protein of Yersinia enterocolitica previously identified on the basis of its ability to confer upon Escherichia coli the phenotype of attachment and invasion of cultured epithelial cells. Here we report an examination of the contribution of ail to the pathogenicity of Y. enterocolitica. A low-copy-number ail plasmid that promoted serum resistance in E. coli HB101 was constructed. The serum resistance phenotype conferred by ail to E. coli was affected by the growth phase of the culture as well as by the gene copy number. In contrast, the copy number of ail (and the relative quantity of Ail) was found to have little effect on the amount of Ail-promoted invasion of cultured epithelial cells. An ail mutant of Y. enterocolitica was constructed and characterized in vitro. This mutant produced no detectable Ail and had a reduced ability to invade CHO cells. Serum resistance of Y. enterocolitica was Ail dependent and was affected by growth phase and ail copy number. The phenotype of the ail mutant was examined in vivo by using a murine model for infection. The ail mutant phenotype was identical to that of the wild-type strain in oral 50% lethal dose studies and early colonization of Peyer's patches as well as in kinetic studies. Western blot (immunoblot) analysis of Ail produced by bacteria growing in vivo at 48 h postinfection indicated that ail was expressed at this time point. Thus, our findings confirm that Ail contributes to the serum resistance and invasion phenotypes of Y. enterocolitica in vitro and indicate that Ail is not required to establish an infection or to cause systemic infection of BALB/c or DBA/2 mice. PMID- 7790068 TI - Sex-determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production. AB - Examination of a wide range of inbred mice of diverse genetic backgrounds and major histocompatibility complex haplotypes revealed a dramatic difference in the susceptibilities of males and females to Toxoplasma gondii infection. Female mice were found to be more susceptible to acute infection, as determined by higher mortality levels, than male mice, while those female mice surviving to have chronic infections harbored more cysts in their brains than did surviving males. This phenomenon was therefore investigated in greater depth immunologically in the BALB/K mouse, a strain showing moderate susceptibility to infection with T. gondii. Plasma tumor necrosis factor alpha (TNF-alpha) levels were elevated in both male and female BALB/K mice on days 8 and 10 postinfection, but not thereafter, with males producing significantly higher levels than females. However, it was not until day 12 postinfection that the first deaths occurred, and these were among female mice, indicating that TNF-alpha production was not responsible for mortality. In vitro examination of T. gondii-specific T-cell proliferative responses from day 15 postinfection onwards revealed significantly higher stimulation indices in male mice than in their female counterparts. This difference was most apparent in splenocyte cultures initiated at day 15 postinfection, where complete suppression of proliferation was noted in the splenocytes from female mice but not from male mice. Analysis of tissue culture supernatants from these cultures revealed distinct differences in the kinetics of production as well as the quantities of gamma interferon (IFN-gamma) and interleukin 10 (IL-10) produced. Spleen cells from male mice produced higher levels of IFN-gamma in the early stages of infection than those from female mice. IFN-gamma levels were highest in the supernatants from male splenocyte cultures initiated at day 15 postinfection. Similar levels of IFN-gamma were not obtained from the supernatants of female splenocyte cultures until day 22 postinfection. IL-10 production, on the other hand, peaked at maximal levels in the cell cultures from both sexes initiated at day 22 postinfection. These results suggest that, in male mice, a rapid response to infection with high levels of TNF-alpha and IFN-gamma helps to control parasite multiplication, after which IL-10 production may be important in down regulating these potentially harmful inflammatory mediators. The failure of female mice to respond quickly in terms of T-cell proliferation and IFN-gamma production compared with their male counterparts may account for their poor survival rates and higher cyst burdens. PMID- 7790070 TI - Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier. AB - We have previously described a new system for the delivery of recombinant antigens in live Salmonella vaccines as genetic fusions to the C terminus of fragment C of tetanus toxin (TetC) driven by the anaerobically inducible nirB promoter. It has been reported that preimmunization with tetanus toxoid (TT) can suppress the antibody response to peptides chemically coupled to TT (epitope specific suppression) in both animals and humans, which could interfere with efficacy of the Salmonella-TetC delivery system. We report that preimmunization of BALB/c mice with TT in alum did not suppress the response to either of two protective antigens of Schistosoma mansoni, the full-length S. mansoni P28 glutathione S-transferase (P28) and a construct consisting of eight tandem copies of the protective peptide comprising amino acids 115 to 131 of P28. The guest antigens were expressed in the aroA Salmonella typhimurium SL3261 vaccine strain as fusions to TetC. Preimmunization with TT 10 weeks before administration of the recombinant salmonellae did not alter the antibody response to the full-length P28, whereas the response to the peptide comprising amino acids 115 to 131 was increased by preimmunization with TT, with the increase seen mainly in the immunoglobulin G1 isotype. The antitetanus response was increased by preimmunization with TT in all groups receiving salmonellae expressing TetC. The results could be important when one is considering the use of the Salmonella-TetC delivery system in populations preimmunized with TT. PMID- 7790071 TI - Role of Yops in inhibition of phagocytosis and killing of opsonized Yersinia enterocolitica by human granulocytes. AB - The virulence plasmid of Yersinia enterocolitica codes for the production of the outer membrane protein YadA and the secretion of several proteins, called Yops, which may play a role in the interaction between granulocytes and this bacterium. We investigated whether the expression of YadA or the secretion of Yops affected the phagocytosis and killing of opsonized Y. enterocolitica by human granulocytes. The rates of phagocytosis and killing of Y. enterocolitica by granulocytes in suspension in the presence of rabbit Yersinia antibodies and complement were determined by microbiological assays. In addition, noningested cell-adherent bacteria were differentiated from ingested yersiniae by immunofluorescence microscopy. Plasmid-bearing opsonized Y. enterocolitica was able to inhibit phagocytosis and killing by human granulocytes. The inhibition of phagocytosis was specific for the plasmid-bearing strain of Y. enterocolitica, since granulocytes were still able to phagocytose and kill Staphylococcus aureus in the presence of Y. enterocolitica. Plasmid-cured Y. enterocolitica was readily phagocytosed and killed by these cells. To investigate the role of YadA or Yops in the inhibition of phagocytosis by granulocytes, the phagocytosis of mutant strains unable to express YadA or to secrete Yops was studied. A Y. enterocolitica mutant unable to secrete Yops lost its ability to inhibit phagocytosis; a mutant expressing only YadA was readily ingested by granulocytes. These results indicate that after attachment of opsonized Y. enterocolitica to granulocytes, Yops play an important role in inhibiting the ingestion of Y. enterocolitica by human granulocytes. PMID- 7790072 TI - Characterization of a novel Mycobacterium bovis secreted antigen containing PGLTS repeats. AB - Serum from naturally infected cattle was used to identify a novel Mycobacterium bovis antigen from an expression library. The first recombinant product identified was a fusion protein with lacZ (55 kDa). A clone containing the whole gene was also obtained. This clone expressed a 38-kDa protein. A rabbit serum against the recombinant antigen reacts in M. bovis supernatants with two proteins of 36 and 34 kDa. The new protein was called P36/P34. The gene cloned has a deduced amino acid sequence with a predicted molecular mass of 28 kDa, showing a characteristic signal sequence for exportation. The protein bears partial homology to a 28-kDa protein from M. leprae. An interesting feature of the P36/P34 sequence is that it contains several PGLTS repeats, which are not present in the M. leprae protein. Antigenic determinants seem also to be conserved between the two proteins because sera from leprosy patients recognized the recombinant M. bovis protein. The discrepancy among the molecular mass deduced from the sequence (28 kDa), that of the recombinant protein in Escherichia coli (38 kDa), and that of the native protein in M. bovis (36 and 34 kDa) could be attributed to posttranslational modifications or to the high proline content that may alter the migration properties of the protein. This antigen seems to be immunodominant during bovine tuberculosis, because 8 of 9 serum specimens from diseased cattle are reactive. The homology among the M. leprae 28-kDa protein, the protein described in this article, and a recently described M. tuberculosis protein suggests the existence of a new protein family in mycobacteria. PMID- 7790069 TI - A Streptococcus mutans mutant that synthesizes elevated levels of intracellular polysaccharide is hypercariogenic in vivo. AB - We used the streptococcal transposon, Tn916 to identify and isolate mutants of Streptococcus mutans with altered intracellular polysaccharide (IPS) accumulation. We report on the isolation and characterization of S. mutans SMS202, a transposon mutant which accumulated the glycogen-like IPS in excess of wild-type levels. Southern blot analysis confirmed a single Tn916 insertion into the SMS202 chromosome. Moreover, quantitative ultrastructural analysis revealed significantly increased concentrations of IPS in SMS202 relative to those of the wild-type progenitor strain, UA130. The activities of ADPglucose pyrophosphorylase (GlgC) and glycogen synthase (GlgA), enzymes required for the biosynthesis of bacterial IPS, were also elevated in the IPS excess mutant. Furthermore, SMS202 was significantly more cariogenic on the molar surfaces of germ-free rats than the wild type (P < 0.01), thus confirming a central role for IPS in S. mutants-induced caries formation. We propose that the increased cariogenic potential of SMS202 is due to constitutive expression of genes which encode glycogen biosynthesis in this oral pathogen. The coordinate expression of GlgC and GlgA along with the results of ongoing nucleotide sequence analysis and Northern hybridization experiments support an operon-like arrangement for the glg genes of this oral pathogen. PMID- 7790073 TI - Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis. AB - HIS-62 is a glycoprotein that has been isolated from the cell wall and cell membrane fraction of the pathogenic fungus Histoplasma capsulatum. It is a target of the cellular immune response to this fungus, and it protects mice against a lethal intravenous inoculum of H. capsulatum yeast cells. In this study, we cloned the gene encoding this antigen to reveal its biological nature and studied the immunological activity of recombinant antigen. The amino acid sequences of the NH2 terminus and internal peptides were obtained by Edman degradation. Degenerate oligonucleotides were used to isolate a gene fragment of HIS-62 by PCR. One 680-bp segment that corresponded to the known peptide sequence was amplified from H. capsulatum DNA. This DNA was used to screen a genomic library, and the full-length gene was isolated and sequenced. The deduced amino acid sequence of the gene demonstrated approximately 70 and approximately 50% identity to heat shock protein 60 (hsp 60) from Saccharomyces cerevisiae and hsp 60 from Escherichia coli, respectively. A cDNA was synthesized by reverse transcription PCR and was expressed in E. coli. Recombinant protein reacted with a monospecific polyclonal rabbit antiserum raised against native HIS-62, with monoclonal HIS-62 reactive T cells, and with splenocytes from mice immunized with viable yeast cells. Moreover, vaccination with the recombinant protein conferred protection in mice against a lethal intranasal inoculation with yeast cells. Thus, HIS-62 is a member of the hsp 60 family, and the recombinant hsp 60 is protective against pulmonary histoplasmosis in mice. PMID- 7790074 TI - Single exposure of mice to Borrelia burgdorferi elicits immunoglobulin G antibodies characteristic of secondary immune response without production of interleukin-4 by immune T cells. AB - Borrelia burgdorferi antigen can elicit immunoglobulins (Igs) characteristic of the primary and secondary immune responses without the contribution of an interleukin-4-producing helper T-cell population. Single exposure of mice to soluble B. burgdorferi antigen elicited both Th1-type and Th2-type antispirochete antibodies. Production of the Ig classes showed different patterns with increasing time postinjection (IgM levels decreased; IgG1, IgG2a, IgG2b, and IgG3 levels increased; IgE was not detected), and Ig patterns were similar to those produced in infected mice. Upon infectious challenge, immunized mice achieved maximal titers of all antispirochete IgG subclasses more quickly than unimmunized mice did. In contrast to the antibody responses which showed both Th1- and Th2 type patterns, T-cell immune response to either immunization or infection was characterized by interleukin-2 and gamma interferon production; interleukin-4 and interleukin-5 were undetectable. Injection with whole spirochetes induced a pattern of antibodies and cytokine production similar to those obtained by injection with soluble antigen. In addition, mouse strains of different major histocompatibility complex backgrounds produced similar patterns of Ig in response to immunization. None of the various parameters of immunization tested resulted in detectable interleukin-4 production by primary or secondary immune T cells. The production of both IgM and IgG1 at early times following a single exposure to spirochete antigen clearly differs from immune responses to haptens or model protein antigens. Production of similar Ig classes in infected and immune mice implies that antigen-specific antibody is responsible for passive immunizing activity found in immune sera. PMID- 7790075 TI - Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form. AB - Cryptococcus neoformans is a pathogenic yeast and a major cause of opportunistic infection in AIDS patients. It is commonly found in an acapsular form in the environment, and infection is likely to occur by inhalation. The lung provides a suitable environment for capsule synthesis, and once encapsulated, C. neoformans becomes resistant to phagocytosis. A stable acapsular mutant of the organism is readily ingested by murine macrophages in vitro, indicating entry via constitutively competent receptors. We demonstrate in this report that this process is inhibitable by particles derived from Saccharomyces cerevisiae that are rich in mannan and beta-glucan, as well as more purified forms of these glycans. Furthermore, ingestion of the acapsular form of C. neoformans induces a range of proinflammatory cytokines, including tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor, which, as we have previously shown, enhance ingestion of serum-opsonized encapsulated C. neoformans in vitro. We demonstrate that ingestion of the acapsular form of the organism also enhances ingestion of the pathogenic encapsulated form. This is dependent on the production of tumor necrosis factor alpha and granulocyte-macrophage colony stimulating factor by the macrophages, since addition of neutralizing antibodies to both cytokines inhibited the observed increase in ingestion. Together, these data demonstrate that ingestion of acapsular C. neoformans is mediated via mannose and beta-glucan receptors on the macrophage surface and that this process activates macrophages for enhanced phagocytosis of the encapsulated form via production of macrophage-derived cytokines. PMID- 7790077 TI - Rats clearing a vaginal infection by Candida albicans acquire specific, antibody mediated resistance to vaginal reinfection. AB - Oophorectomized, estrogen-treated rats were susceptible to experimental vaginal infection by Candida albicans. After spontaneous clearing of the primary infection, the animals were highly resistant to a second vaginal challenge with the fungus. The vaginal fluid of Candida-resistant rats contained antibodies directed against mannan constituents and secretory aspartyl proteinase(s) of C. albicans and was capable of transferring a degree of anti-Candida protection to naive, nonimmunized rats. This passive protection was mediated by the immunoglobulin fraction of the vaginal fluid and was substantially abolished by preabsorption of the vaginal fluid with C. albicans, but not with Saccharomyces cerevisiae, cells. Vaginal anti-mannan antibodies were also produced by active immunization with heat-killed cells of C. albicans or with a mannan extract when administered via the vaginal route. The protection conferred was comparable to that resulting from clearing of the primary infection. In summary, the data suggest that acquired anticandidal protection in this vaginitis model is mediated at least in part by antibodies, among which those directed against the mannan antigen(s) might play a dominant role. PMID- 7790076 TI - Characterization of an antiproliferative surface-associated protein from Actinobacillus actinomycetemcomitans which can be neutralized by sera from a proportion of patients with localized juvenile periodontitis. AB - The gentle agitation of suspensions of Actinobacillus actinomycetemcomitans serotype a, b, or c in saline resulted in the release of a proteinaceous surface associated material (SAM) which produced a dose-dependent inhibition of tritiated thymidine incorporation by the osteoblast-like cell line MG63 in culture. This cell line was sensitive to low concentrations of SAM (50% inhibitory concentration, 200 ng/ml for serotype c). Immunoglobulin G antibodies to constituents of the SAM were found in the blood of patients with localized juvenile periodontitis (LJP). Sera from 9 of 16 patients with LJP significantly neutralized the antiproliferative activity of the SAM, while sera from 15 controls, with no evidence of periodontal disease, were unable to neutralize this activity. Neutralization was not directly related to the patient's antibody titer to the whole SAM. Characterization of the antiproliferative activity in the SAM demonstrated that it was not cytotoxic and was heat and trypsin sensitive. The active component separated in a well-defined peak in anion-exchange high performance liquid chromatography (HPLC) which, when further analyzed by size exclusion HPLC, revealed a single active peak, which had an apparent molecular mass of approximately 8 kDa. The lipopolysaccharide from A. actinomycetemcomitans was only weakly active. SAM from Porphyromonas gingivalis W50 and Eikenella corrodens NCTC 10596 did not exhibit any antiproliferative activity with this cell line, even at concentrations as high as 10 micrograms/ml. This study has shown that SAM from A. actinomycetemcomitans contains a potent antiproliferative protein whose activity can be neutralized by antibodies in the sera from some patients with LJP. PMID- 7790079 TI - Effects of the two varieties of Cryptococcus neoformans cells and culture filtrate antigens on neutrophil locomotion. AB - Cryptococcus neoformans var. gattii (serotype B and C) isolates have a relative predilection for immunocompetent hosts, and C. neoformans var. neoformans (serotype A and D) isolates have a relative predilection for immunocompromised hosts, suggesting that normal host resistance to the former may be relatively inefficient compared with that to the latter variety. In order to assess the possibility that normal cellular host defense is inadequate in protecting against C. neoformans var. gattii, we compared the two varieties of C. neoformans cells and their culture filtrate antigens (CneF) with respect to effects on neutrophil (polymorphonuclear leukocyte [PMN]) locomotion. In a 48-well modified Boyden chamber, the cells and CneF of C. neoformans var. neoformans (serotype A and D) isolates stimulated chemotaxis and chemokinesis of human PMN and activated a complement component(s) in pooled human serum to become a chemoattractant(s) for human PMN. In contrast, the cells and CneF of C. neoformans var. gattii (serotype B and C) isolates did not stimulate chemotaxis or chemokinesis in human PMN but rather inhibited chemokinesis and chemotactic responses of PMN to pooled human serum and formylmethionyl leucyl phenylalanine. Neither of the CneF from the C. neoformans var. gattii isolates was cytotoxic to PMN. Furthermore, with the mouse model, we found that CneF from C. neoformans var. neoformans caused migration of PMN into gelatin sponges implanted in naive and immunized mice, whereas CneF from C. neoformans var. gattii inhibited PMN migration into sponges. Our results, combined with findings of others showing reduced PMN infiltration in lungs of mice infected with C. neoformans var. gattii compared with PMN infiltration in lungs of mice infected with C. neoformans var. neoformans, indicate that the relative inadequacy of normal host resistance mechanisms to prevent infection with C. neoformans var. gattii results, in part, from inhibition of PMN migration to the site of the organism. PMID- 7790078 TI - Putative glycoprotein and glycolipid polymorphonuclear leukocyte receptors for the Actinomyces naeslundii WVU45 fimbrial lectin. AB - Recognition of receptors on sialidase-treated polymorphonuclear leukocytes (PMNs) by the Gal/GalNAc lectin associated with the type 2 fimbriae of certain strains of actinomyces results in activation of the PMNs, phagocytosis, and destruction of the bacteria. In the present study, plant lectins were utilized as probes to identify putative PMN receptors for the actinomyces lectin. The Gal-reactive lectin from Ricinus communis (RCAI), the Gal/GalNAc-reactive lectins from R. communis (RCAII) and Bauhinia purpurea (BPA), as well as the Gal beta 1-3GalNAc specific lectins from Arachis hypogaea (PNA) and Agaricus bisporus (ABA) inhibited killing of Actinomyces naeslundii WVU45 by sialidase-treated PMNs. These five lectins detected a 130-kDa surface-labeled glycoprotein on nitrocellulose transfers of PMN extracts separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. This glycoprotein was revealed only after treatment of the transfers with sialidase, a condition analogous to the sialidase dependence of the lectin-mediated biological responses of the PMNs to the actinomyces. The mannose-reactive lectin concanavalin A did not inhibit killing of the actinomyces and failed to detect the 130-kDa glycoprotein but did block PMN-dependent killing of Escherichia coli B, a bacterium that possesses mannose sensitive fimbriae. Therefore, the PMN glycoprotein receptor for A. naeslundii is clearly distinct from those recognized by E. coli. Two major putative glycolipid receptors were also identified by actinomyces and RCAI overlays on sialidase treated thin-layer chromatograms of PMN gangliosides. Thus, both a 130-kDa glycoprotein and certain gangliosides are implicated in the attachment of the actinomyces to PMNs. PMID- 7790080 TI - Mucosal immunogenicity of polysaccharides conjugated to a peptide or multiple antigen peptide containing T- and B-cell epitopes. AB - In this study we investigated the mucosal and systemic responses to two T-cell independent polysaccharides, a serogroup f polysaccharide (formed of rhamnose glucose polymers [RGPs]) from Streptococcus mutans OMZ 175 and a mannan from Saccharomyces cerevisiae, covalently conjugated either to a linear peptide (peptide 3) or to a multiple-antigen peptide (MAP), both derived from S. mutans protein SR, an adhesin of the I/II protein antigen family of oral streptococci. Peptide 3 and MAP, which contained at least one B- and one T-cell epitope, were tested as carriers for the polysaccharides and as protective immunogens. Intragastric intubation of rats with the conjugates (RGPs-peptide 3, RGPs-MAP, mannan-peptide 3, and mannan-MAP) associated with liposomes produced salivary immunoglobulin A (IgA) antibodies which reacted with RGPs or mannan, peptide 3 or MAP, protein SR, and S. mutans or S. cerevisiae cells. Administration of conjugate boosters to the animals showed that both carriers conjugated to the polysaccharides were able to induce, in immunized animals, a salivary antipolysaccharide IgA memory. In contrast, animals primed and challenged with unconjugated polysaccharide showed no anamnestic response. Rats orally immunized with the conjugates also developed systemic primary antipolysaccharide and antipeptide IgM antibody responses which were characterized by a switch from IgM to IgG during the course of the secondary response. Data presented here demonstrated that both peptide 3 and the MAP construct can act as good carriers for orally administered polysaccharides. Unexpectedly, the use of a MAP did not further improve the immunogenicity of polysaccharides at the mucosal level; nevertheless, such a construct should be of great interest in overcoming the problem of genetic restriction induced by linear peptides. PMID- 7790081 TI - A Mycobacterium leprae gene encoding a fibronectin binding protein is used for efficient invasion of epithelial cells and Schwann cells. AB - Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen. M. leprae can infect a variety of cells in vivo, including epithelial cells, muscle cells, and Schwann cells, in addition to macrophages. The ligand-receptor interactions important in the attachment and ingestion of M. leprae by these nonmacrophage cells remains unknown. Fibronectin (FN) significantly enhances both attachment and ingestion of M. leprae by epithelial and Schwann cell lines. We cloned an M. leprae FN binding protein (FN attachment protein [FAP]) distinct from the 85ABC complex which has been shown previously to bind FN. The FAP open reading frame predicts a protein of 29.5 kDa with a 39-amino-acid signal peptide and was previously described as an antigen in leprosy patients. M. leprae FAP has homologies in M. vaccae, M. avium, and M. tuberculosis, as determined by Southern blotting and direct peptide analysis. Both anti-FAP antibodies and an Escherichia coli-expressed recombinant protein significantly blocked M. leprae attachment and internalization by T-24, an epithelial cell line, and JS1, a Schwann cell line. These data suggest that FN can be a bridging opsonic ligand for attachment of mycobacteria to nonphagocytes and that FAP plays an important role in this process. This may be an important step in the initiation of M. leprae infection in vivo. PMID- 7790082 TI - Alternate routes of invasion may affect pathogenesis of Salmonella typhimurium in swine. AB - Transmission of Salmonella typhimurium in swine is traditionally believed to occur by the fecal-oral route, with invasion through the intestinal wall and Peyer's patches. However, involvement of the upper respiratory tract may be equally important. An esophagotomy was performed on 6- to 8-week-old pigs. Esophagotomized pigs were challenged intranasally with 10(9) CFU of S. typhimurium cells and necropsied at 3, 6, 12, and 18 h postinoculation (p.i.). By 3 h p.i., S. typhimurium was recovered from cecum, colon, head, and thoracic tissues and from the middle ileum involving a large number of Peyer's patches. The ileocolic lymph nodes and ileocolic junction were not positive for S. typhimurium until 6 and 12 h p.i., respectively. Additional pigs were inoculated transthoracically with 10(9) CFU of S. typhimurium and necropsied at 3 and 18 h p.i. By 3 h p.i., all tissues were positive for S. typhimurium. Tonsil explants seeded with 10(9) CFU of S. typhimurium indicated that within 6 h p.i., S. typhimurium was located within the tonsilar crypts. These data show that after intranasal inoculation, S. typhimurium rapidly appears in the gut tissues and suggest that the tonsils and lung may be important sites for invasion and dissemination of Salmonella species. PMID- 7790083 TI - Monoclonal antibodies against Haemophilus lipopolysaccharides: clone DP8 specific for Haemophilus ducreyi and clone DH24 binding to lacto-N-neotetraose. AB - Mouse monoclonal antibodies (MAbs) DP8 [immunoglobulin G1(kappa)] and DH24 [immunoglobulin M(kappa)], which are specific for Haemophilus ducreyi lipopolysaccharide (LPS), were generated by fusing mouse myeloma NS0 cells with spleen cells of BALB/c mice immunized with a total membrane preparation of H. ducreyi. MAb DP8 reacted in whole-cell enzyme immunoassay (EIA) and colony dot immunoblotting with all 50 strains of H. ducreyi but not with any other bacteria tested, which suggests an exposed and species-specific epitope on the H. ducreyi cell surface. This conclusion was supported by the finding that DP8 bound to all six H. ducreyi LPSs tested but not to any of the Haemophilus influenzae or enterobacterial LPSs or synthetic glycoconjugates. The MAb DH24 bound to 43 of 50 strains of H. ducreyi and to few strains of H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as evaluated by whole-cell EIA and colony dot immunoblotting. The MAb DH24 reacted with five of the six H. ducreyi LPSs tested and with the lacto-N-neotetraose (Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1- >4Glc) series of synthetic glycoconjugates, as determined by EIA. By using polysaccharides obtained after both mild acidic hydrolysis and strong alkali treatment and dephosphorylated samples as inhibitors of the MAbs binding to H. ducreyi LPS antigens, it could be shown that phosphate groups were essential for the binding of DP8 to LPS but that they did not affect antigenic recognition by DH24. None of the MAbs bound to isolated lipid A, but aggregation caused by the fatty acids of lipid A was essential for epitope recognition. PMID- 7790084 TI - Helicobacter pylori-induced gastritis in the domestic cat. AB - Helicobacter pylori has been cultured from the inflamed gastric mucosae of naturally infected cats; the lesions in H. pylori-infected cat stomachs mimic many of the features seen in H. pylori-infected human stomachs. To determine whether H. pylori-negative specific-pathogen-free cats with normal gastric mucosae were susceptible to colonization by this bacterium and whether gastritis developed after infections, four H. pylori-negative cats treated with cimetidine were orally dosed three times with 3 ml (1.5 x 10(8) CFU/ml) of H. pylori every 4 days. All four cats became persistently colonized as determined by gastric cultures and PCRs from serial gastric biopsy samples and necropsy samples at 7 months postinfection. H. pylori was not isolated from the two control cats, nor were their gastric tissues positive by PCR; one of the two cats had a few focal lymphocytic aggregates in the body submucosa, whereas the second cat had a normal gastric mucosa. All four H. pylori-infected cats had multifocal gastritis consisting of lymphoid aggregates plus multiple large lymphoid nodules, which were most noticeable in the antral mucosa. In addition, one H. pylori-infected cat had a moderate diffuse infiltration of polymorphonuclear leukocytes in the subglandular region of the antrum. H. pylori-like organisms were focally distributed in glandular crypts of the antrum. Two of the H. pylori-infected cats had significant (eightfold) increases over baseline in levels of immunoglobulin G H. pylori serum antibody. The H. pylori isolates from the four experimentally infected cats had restriction fragment length polymorphism patterns specific for the flaA gene that were identical to those of the inoculating strain. H. pylori readily colonizes the cat stomach and produces persistent gastritis. PMID- 7790085 TI - Protein Hpn: cloning and characterization of a histidine-rich metal-binding polypeptide in Helicobacter pylori and Helicobacter mustelae. AB - Helicobacter pylori is a human gastrointestinal pathogen involved in gastritis, duodenal ulcers, and gastric neoplasia. This microorganism produces large amounts of a urease which, like all known ureases, has nickel in the active site. We have identified a protein in clinical isolates of H. pylori and an identical protein in the ferret pathogen Helicobacter mustelae that strongly binds Ni2+ and Zn2+. This protein has been named Hpn to emphasize its origins in H. pylori and its affinity for nickel. The encoding hpn gene, cloned and expressed in Escherichia coli ER1793, has an open reading frame (180 bp) that specifies a protein with a calculated molecular mass of 7,077 Da and with the same amino-terminal sequence as that of wild-type Hpn. The deduced sequence of Hpn consists of 60 amino acids, of which 28 (47%) are histidines. The hpn gene does not map with the urease gene cluster on the H. pylori chromosome. An Hpn-negative, isogenic H. pylori strain, generated by hpn gene deletion and grown on blood agar, had the same urease activity that wild-type cells did. Thus, the role of Hpn in helicobacters is unknown. PMID- 7790087 TI - Enhancement of uptake of lipopolysaccharide in macrophages by the major outer membrane protein OmpA of gram-negative bacteria. AB - Monoclonal antibodies (MAb) to lipopolysaccharide (LPS) and to the major outer membrane protein OmpA from Proteus mirabilis were generated and used to monitor the kinetics of uptake in macrophages of LPS as well as LPS bound to OmpA. Uptake was measured by a modified enzyme-linked immunosorbent assay (ELISA) in a microtiter culture system. The MAb were of various immunoglobulin G subclasses and showed strong reactivities with their antigens. Four hybridoma clones recognizing LPS and three recognizing OmpA from P. mirabilis 19 were selected for the present study on the basis of reactions in ELISA and Western blot (immunoblot) analyses. In the uptake assay, it was possible to differentiate between antigen on the cell surface and antigen which had been internalized. Uptake of LPS by macrophages was relatively rapid during the first 4 h of culture and then progressed more slowly over the remaining 24-h observation period. The level of detection of LPS in this assay system was in the nanogram range. When macrophages were pulsed with LPS for 30 min and subsequently washed to remove antigen not bound to the cells, the amount of LPS detectable on the macrophage surface decreased progressively for 3 h after the pulse, which indicated internalization of the antigen. Thereafter, LPS rose to an increased level on the cell surface. The rate of uptake of LPS was more rapid when it was in complex with OmpA. When the fate of OmpA was monitored in the same LPS-protein complexes by use of MAb to OmpA in a pulse experiment, the level of protein measured on the cell surface decreased after an initial rise, which again indicated internalization, but the protein did not reappear on the cell surface in a form detectable with the MAb. Compared with the LPS monitoring system, detection of OmpA associated with macrophages was weak, although the MAb to OmpA reacted strongly with the protein in the ELISA and Western blot analyses. PMID- 7790086 TI - Heterologous antigen expression in Vibrio cholerae vector strains. AB - Live attenuated vector strains of Vibrio cholerae were derived from Peru-2, a Peruvian El Tor Inaba strain deleted for the cholera toxin genetic element and attRS1 sequences, which was developed as a live, oral vaccine strain. A promoterless gene encoding the Shiga-like toxin I B subunit (slt-IB) was inserted in the V. cholerae virulence gene irgA by in vivo marker exchange, such that slt IB was under transcriptional control of the iron-regulated irgA promoter. slt-IB was also placed under transcriptional control of the V. cholerae heat shock promoter, htpGp, and introduced into either the irgA or lacZ locus, or both loci, on the chromosome of Peru-2, generating JRB10, JRB11, or JRB12, respectively. A new technique was used to perform allelic exchange with lacZ. This method uses plasmid p6891MCS, a pBR327 derivative containing cloned V. cholerae lacZ, to insert markers of interest into the V. cholerae chromosome. Recombinants can be detected by simple color screening and antibiotic selection. In vitro measurements of Slt-IB produced by the vector strains suggested that expression of Slt-IB from the irgA and htpG promoters was synergistic and that two copies of the gene for Slt-IB increased expression over a single copy. The V. cholerae vectors colonized the gastrointestinal mucosa of rabbits after oral immunization, as demonstrated by very high serum antibody responses to V. cholerae antigens. Comparison of the serologic responses to the B subunit of cholera toxin (CtxB) following orogastric inoculation either with the wild-type C6709 or with Peru-10, a strain containing ctxB regulated by htpGp, suggested that both the cholera toxin and heat shock promoters were active in vivo, provoking comparable immunologic responses. Orogastric inoculation of rabbits with vector strains evoked serum immunoglobulin G (IgG) responses to Slt-IB in two of the four strains tested; all four strains produced biliary IgA responses. No correlation was observed between the type of promoter expressing slt-IB and the level of serum IgG or biliary IgA response, but the vector strain containing two copies of the gene for slt-IB evoked greater serum IgG responses than strains containing a single copy, consistent with the increased expression of Slt-IB from this strain observed in vitro. A comparison of the serum and biliary antibody responses to Slt-IB expressed from htpGp versus CtxB expressed from the same promoter suggested that CtxB is a more effective orally delivered immunogen. PMID- 7790088 TI - Characterization of a recombinant pneumolysin and its use as a protein carrier for pneumococcal type 18C conjugate vaccines. AB - Pneumolysin from Streptococcus pneumoniae was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified by affinity and hydroxylapatite chromatography. The purified recombinant pneumolysin (rPL), with a molecular mass of 53 kDa, had a specific activity of 3 x 10(5) hemolytic units per mg of protein on rabbit erythrocytes and reacted identically in immunodiffusion with the antisera against native pneumolysin. The rPL was used as a protein carrier to prepare conjugate vaccine with pneumococcal type 18C polysaccharide (PS18C). The PS18C was directly coupled to rPL by reductive animation or was indirectly coupled to rPL via a spacer molecule, adipic acid dihydrazide. The conjugates were nontoxic for mice and guinea pigs at 100 micrograms per dose. The immunogenicity and protective efficacy of both conjugates were tested in mice. A single dose of either of the vaccines elicited a rise in immunoglobulin G antibody production; after two booster injections of the vaccines, statistically significant booster responses (P < 0.001) to both rPL and PS18C were produced. The sera containing the antibodies to rPL were capable of neutralizing the hemolytic activity of rPL to rabbit erythrocytes and the cytotoxicity of rPL to bovine pulmonary endothelial cells. Immunization with the conjugate vaccines conferred statistically significant protection in mice against lethal challenge with type 18C pneumococci. PMID- 7790089 TI - Antibody response that protects against disseminated candidiasis. AB - We previously showed that surface mannans of Candida albicans function as adhesins during yeast cell attachment to mouse splenic marginal zone macrophages. The mannan adhesin fraction was encapsulated into liposomes and used to vaccinate mice over a 5- to 6-week period. Circulating agglutinins specific for the fraction correlated with increased resistance to disseminated candidiasis. Antiserum from vaccinated animals protected naive BALB/cByJ mice against C. albicans serotype A and B strains and Candida tropicalis. Antiserum also protected SCID mice against disseminated disease. The serum protective ability was stable at 56 degrees C, but this ability was adsorbed by C. albicans cells. The antiserum was divided into three fractions after separation by high performance liquid chromatography. One fraction contained all of the agglutinin activity and transferred resistance to naive mice. A second fraction also transferred resistance. Two monoclonal antibodies (MAbs) specific for candidal surface determinants were obtained. MAb B6.1 is specific for a mannan epitope in the adhesin fraction, and MAb B6 is specific for a different epitope in the fraction. Both MAbs are immunoglobulin M, and both strongly agglutinate candidal cells, but only MAb B6.1 protected both normal and SCID mice against disseminated candidiasis. In one experiment, 10 normal mice were given MAb B6.1 and challenged with yeast cells. Six mice survived the 67-day observation period; 4 of the survivors were cured as evidenced by the lack of CFU in the kidney and spleen. Our studies show that antibodies against certain cell surface antigens of C. albicans help the host resist disseminated candidiasis. PMID- 7790090 TI - Human peripheral blood CD4+ and CD8+ T cells express Th1-like cytokine mRNA and proteins following in vitro stimulation with heat-inactivated Brucella abortus. AB - Defining the pattern of lymphokine production associated with Brucella abortus is critical for advancing the development of B. abortus as a vaccine carrier. In the present study we investigated the ability of heat-inactivated B. abortus or lipopolysaccharide from B. abortus to induce lymphokine production from purified human T cells in vitro. Gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 induction was assayed by mRNA-specific PCR and by enzyme-linked immunosorbent assay and bioassay for protein production. Following depletion of monocytes and B cells, B. abortus increased IFN-gamma and IL-2 mRNA expression in purified T cells compared with expression in unstimulated cells. In contrast, no IL-5 mRNA expression and only transient low-level IL-4 mRNA expression and no IL 4 protein secretion were detected. Phytohemagglutinin or phorbol myristate acetate plus ionomycin induced mRNA and protein for all these cytokines. Similar results were obtained with LPS purified from B. abortus. Removal of NK cells did not reduce lymphokine production, and enriched NK cells did not express IFN-gamma mRNA or secrete IFN-gamma protein in response to B. abortus, indicating that NK cells were not the responding population. Both CD4+ and CD8+ populations produced IFN-gamma and IL-2 in response to B. abortus. Preincubation of resting T cells with B. abortus or LPS from B. abortus for 7 days induced their differentiation into Th1-like cells as judged by their subsequent lymphokine response to phorbol myristate acetate plus ionomycin. These results suggest that B. abortus can induce differentiation of Th0 into Th1-type cells. PMID- 7790092 TI - Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli. AB - A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intraperitoneal administration of 10(6) 50% lethal doses (ID50) of serotype A toxin. The same mice survived when challenged with 3 LD50 of botulinum toxin serotype E but died when challenged with 10 LD50 of serotype E or 3 LD50 of serotype B. Purified fragment C was compared with the botulinum toxoid vaccine in a vaccination and challenge study. Fragment C was as efficacious in protecting against challenge with active botulinum neurotoxin serotype A as the toxoid vaccine. This recombinant protein product has many properties that make it a good candidate for human use to protect against botulinum toxin. PMID- 7790091 TI - iactA of Listeria ivanovii, although distantly related to Listeria monocytogenes actA, restores actin tail formation in an L. monocytogenes actA mutant. AB - A gene homologous to the actA gene of Listeria monocytogenes was cloned from Listeria ivanovii (strain CLIP257) by chromosome walking starting from the ilo gene that encodes the pore-forming toxin ivanolysin. The nucleotide sequence revealed that this gene, named iactA, encodes a protein of 1,044 amino acids (IactA) comprising a central region with seven highly conserved tandem proline rich repeats of 47 amino acids. Although IactA and ActA share an overall similar structure, these two proteins are only distantly related. Like ActA, IactA migrates aberrantly on sodium dodecyl sulfate gels. When expressed in an L. monocytogenes actA deletion mutant strain, iactA restored actin polymerization. PMID- 7790094 TI - The Salmonella dublin virulence plasmid mediates systemic but not enteric phases of salmonellosis in cattle. AB - Plasmid-bearing and plasmid-free isolates and a plasmid-cured strain of Salmonella dublin were compared for virulence in calves. The plasmid-bearing strains were highly virulent, causing severe enteric and systemic disease with high mortality. In contrast, the plasmid-free strains caused diarrhea but only low mortality. The infection kinetics of a wild-type and a derivative plasmid cured strain were compared. Both strains were isolated in high numbers from intestinal sites at 3 and 6 days after oral challenge and were isolated at comparable frequencies from systemic sites at 3 days, but not at 6 days, when the wild-type strain was predominant. The strains were equally invasive in intestinal epithelia with and without Peyer's patch and elicited comparable secretory and inflammatory responses and intestinal pathology in ligated ileal loops. The effect of the virulence plasmid on growth kinetics and on the outer membrane protein profile was assessed in an in vivo growth chamber. The virulence plasmid did not influence either extracellular growth or the expression of major outer membrane proteins. These observations demonstrate that the virulence plasmid is not involved in either the enteric phase of infection or the systemic dissemination of S. dublin but probably mediates the persistence of S. dublin at systemic sites. PMID- 7790093 TI - Characterization of intestinal invasion by Salmonella typhimurium and Salmonella dublin and effect of a mutation in the invH gene. AB - The relative levels of invasiveness of two bovine isolates each of Salmonella typhimurium and Salmonella dublin and of invH mutants of S. typhimurium were determined in MDCK and Int 407 cultured-cell assays and in bovine ileal loops. S. dublin was found to be significantly less invasive in cultured cells than S. typhimurium, but this difference was not observed in bovine intestines. The invH mutants exhibited a significant reduction in invasion in both cultured cells and bovine intestines. The invasive phenotypes of the strains were confirmed by fluorescent microscopy and scanning and transmission electron microscopy. The wild-type strains were observed in the laminae propriae of the intestinal villi, while in contrast the invH mutants were generally associated with the enterocyte layer. The degree of damage in the bovine ileum was related to the magnitude of the invasion. There was no difference in the amount of S. typhimurium or S. dublin recovered from the bovine ileum either with or without Peyer's patches 3 h after inoculation of the loop. PMID- 7790095 TI - Protection against local Shigella sonnei infection in mice by parenteral immunization with a nucleoprotein subcellular vaccine. AB - Nucleoprotein subcellular (NPS) vaccine, consisting of ribosome-bound O polysaccharide, was prepared from avirulent Shigella sonnei. NPS vaccine was tested for safety and protective activity in the mouse intranasal challenge model of Shigella infection. The vaccine was nontoxic when injected in doses up to 10,000 micrograms, and a single subcutaneous injection of as little as 0.1 micrograms gave significant protection against a lethal intranasal challenge with S. sonnei. These data demonstrate the induction of local protective immunity by parenteral immunization, support the concept of the ribosome as a potent vaccine vector, and give additional evidence for the protective activity of the NPS vaccine against Shigella infection. PMID- 7790097 TI - Salmonella typhimurium displays normal invasion of mice with defective epidermal growth factor receptors. AB - The role of the epidermal growth factor (EGF) receptor in cell invasion by Salmonella typhimurium was examined in vitro and in vivo by using waved-2 mice which express an EGF receptor with reduced kinase activity. S. typhimurium invaded fibroblasts from waved-2 mice as efficiently as fibroblasts from wild type control animals. In vivo, S. typhimurium both invaded the gastrointestinal tract and penetrated through to the spleen of waved-2 mice. Our studies suggest that the EGF receptor has only a limited role, if any, in cell invasion by S. typhimurium. PMID- 7790096 TI - Shiga toxin-associated hemolytic uremic syndrome: effect of sodium butyrate on sensitivity of human umbilical vein endothelial cells to Shiga toxin. AB - Escherichia coli O157:H7-related vascular damage such as hemolytic uremic syndrome is believed to require the Shiga-like toxins. This study demonstrated that sodium butyrate sensitized human umbilical vein endothelial cells to Shiga toxin and increased the expression of Shiga toxin receptor, globotriaosylceramide (Gb3), on human umbilical vein endothelial cells. PMID- 7790098 TI - Phenotypic modulation of gonococcal lipooligosaccharide in acidic and alkaline culture. AB - Neisseria gonorrhoeae infects a diverse array of niches in its human host, which expose the organism to dramatic variations in pH. We examined growth and lipooligosaccharide expression of two gonococcal strains in liquid and solid cultures under acidic, neutral, and alkaline conditions. Growth rates in broth were similar under the three conditions, and the pH remained fairly constant throughout the growth cycle. Altered lipooligosaccharide expression at the different pHs was noted in both plate- and broth-grown organisms. PMID- 7790099 TI - Different forms of streptolysin O produced by Streptococcus pyogenes and by Escherichia coli expressing recombinant toxin: cleavage by streptococcal cysteine protease. AB - To resolve apparent discrepancies in the literature, N-terminal sequences of the active high- and low-molecular-weight (high- and low-M(r)) forms of native streptolysin O (nSLO) purified from Streptococcus pyogenes culture supernatants and of the similar-size high- and low-M(r) forms of recombinant SLO (rSLO) found in the periplasm of Escherichia coli expressing a cloned slo gene were determined. The high-M(r) forms of nSLO and rSLO are identical, reflecting removal of a 31-residue signal peptide, but the similar-size low-M(r) forms are very different. Removal of C-terminal sequences by proteases in the E. coli periplasm produces an inactive low-M(r) form of rSLO. In contrast, an active low M(r) form of nSLO is produced by proteolytic cleavage between the N-terminal residues Lys-77 and Leu-78, which was shown to correspond to an extremely sensitive cleavage site for the pyrogenic exotoxin B-derived streptococcal cysteine protease. PMID- 7790100 TI - Directed genomic integration in Actinobacillus actinomycetemcomitans: generation of defined leukotoxin-negative mutants. AB - To develop targeted gene integration in the periodontal pathogen Actinobacillus actinomycetemcomitans, a ColE1-based, spectinomycin-resistant plasmid containing a segment of the leukotoxin gene was electroporated into strain JP2. In all of the stable spectinomycin-resistant transformants that arose, the plasmid had recombined into the genomic leukotoxin locus since ColE1-based vectors cannot replicate extrachromosomally in A. actinomycetemcomitans. Directed genomic integration was then used to construct a leukotoxin-negative strain by transforming the leukotoxin-producing strain JP2 with a ColE1-based plasmid containing an internal fragment of the leukotoxin gene. Cytotoxicity assays proved that these transformants had < 0.1% of the leukotoxin activity of the parental strain. These results demonstrate that integration-based approaches can be used for generating isogenic mutants in specific virulence genes in A. actinomycetemcomitans. PMID- 7790101 TI - Characterization of the human immunoglobulin G Fc-binding activity in Prevotella intermedia. AB - Many pathogenic bacteria possess cell surface receptors which can bind immunoglobulins via the Fc portion. The aim of this study was to characterize the human immunoglobulin G (IgG) Fc-binding activity of Prevotella intermedia, a suspected etiologic agent of adult chronic periodontitis. The Fc-binding activity of P. intermedia on whole cells and on extracellular vesicles was demonstrated. Incubation of P. intermedia cells in the presence of Zwittergent 3-14 allowed complete solubilization of the Fc receptor from the cell surface. This cell envelope extract was thus used to characterize the Fc-binding activity. A microtiter plate assay using alkaline phosphatase-labeled Fc fragments showed that preincubation of the cell envelope extract with human IgG, human IgG Fc fragments, or human serum completely inhibited the Fc-binding activity. Partial inhibition was obtained with human IgG F(ab')2 fragments, whereas no inhibition occurred following preincubation with human IgA, carbohydrates, and selected proteins. Preincubation of the cell envelope extract with IgG from a variety of animals demonstrated that rabbit, mouse, rat, goat, and sheep IgG did not inhibit Fc-binding activity, whereas cow, pig, and dog IgG partially inhibited Fc-binding activity. A strong inhibition comparable to that obtained with human IgG was noted with monkey IgG. The Fc receptor of P. intermedia is thus different from the six types previously reported in other nonoral bacteria. Polyacrylamide gel electrophoresis and Western blotting (immunoblotting) analysis of the cell envelope extract revealed a major band with a molecular mass of approximately 65 kDa which reacted with peroxidase-labeled human IgG Fe fragments. Transmission electron microscopy showed a uniform distribution of the Fc receptor on the bacterial surface, as revealed by gold labeling. The Fc-binding activity demonstrated in this study may act as an additional virulence factor for P. intermedia by reducing IgG reactions with the bacterial cell. PMID- 7790102 TI - Role of interleukin-6 in T-cell activation during primary and secondary infection with Listeria monocytogenes. AB - Injection of recombinant interleukin-6 (IL-6) into mice enhances recovery from infection with Listeria monocytogenes. In this study, the role of IL-6 during primary and secondary Listeria infection was further tested. Neutralization of IL 6 by polyclonal antibody exacerbated primary infection and significantly delayed gamma interferon production by cultured spleen cells. In contrast, administration of anti-IL-6 antibody at the time of secondary infection did not affect the recovery of mice from infection or gamma interferon production, showing that activated T cells are not dependent on IL-6. PMID- 7790103 TI - Enhancement of macrophage microbicidal activity: supplemental arginine and citrulline augment nitric oxide production in murine peritoneal macrophages and promote intracellular killing of Trypanosoma cruzi. AB - The generation of nitric oxide (NO) is largely responsible for the intracellular killing of Trypanosoma cruzi by activated macrophages. The present study was carried out to determine whether the production of NO by activated murine macrophages cultured in physiologic levels of arginine can be augmented by increasing the availability of arginine, the substrate for NO biosynthesis. Increased exogenous arginine or citrulline resulted in a significant increase in NO production and complete clearance of the parasites by activated macrophages. As citrulline fully substituted for arginine in supporting NO production and trypanocidal activity, these results demonstrate the expression of a highly active citrulline-NO cycle in activated macrophages and that levels of arginine in plasma are limiting with respect to both NO production and trypanocidal activity in these cells. The results indicate that increasing plasma substrate levels for both arginine and NO biosynthesis may represent a means of enhancing microbicidal activity in vivo. PMID- 7790104 TI - Cloning and characterization of a protective outer membrane lipoprotein of Actinobacillus pleuropneumoniae serotype 5. AB - The gene encoding an outer membrane lipoprotein (omlA) of Actinobacillus pleuropneumoniae serotype 5 was cloned, and the protein was expressed in Escherichia coli. One open reading frame of 1,104 bp was detected that encoded a protein (OmlA) with a predicted molecular mass of 40 kDa. A comparison with the omlA gene and the corresponding protein of A. pleuropneumoniae serotype 1 (G.-F. Gerlach, C. Anderson, S. Klashinsky, A. Rossi-Kampos, A.A. Potter, and P.J. Wilson, Infect. Immun. 61:565-572, 1993) revealed that the nucleic acid sequences had an overall sequence identity of 62.9% and the deduced amino acid sequences showed a sequence agreement of 57.3%. Both proteins were antigenically distinct. In a Western blot (immunoblot) analysis using a specific antiserum against A. pleuropneumoniae serotype 5 OmlA, a homologous protein was detected in the reference strains of A. pleuropneumoniae serotypes 5A, 5B, and 10. Pigs immunized with this recombinant protein were protected from death in an aerosol challenge experiment with an A. pleuropneumoniae serotype 5 isolate. PMID- 7790105 TI - Inhibition of Chlamydia pneumoniae growth in HEp-2 cells pretreated with gamma interferon and tumor necrosis factor alpha. AB - An in vitro culture system was used to study the effects of increasing concentrations of human cytokines on the intracellular replication of Chlamydia pneumoniae. HEp-2 cell monolayers, pretreated for 24 h with 200 U of human recombinant gamma interferon (IFN-gamma) per ml restricted the intracellular replication of C. pneumoniae. Tumor necrosis factor alpha (TNF-alpha; 25 ng/ml) exhibited a synergistic effect with IFN-gamma by reducing the concentration of IFN-gamma necessary to restrict intracellular growth to 100 U/ml. The addition of 200 micrograms of tryptophan per ml significantly reversed the inhibitory effects of IFN-gamma and TNF-alpha, suggesting involvement of the indoleamine-2,3 dioxygenase pathway in the restriction process. PMID- 7790106 TI - Melanoma and use of sunscreens: an Eortc case-control study in Germany, Belgium and France. The EORTC Melanoma Cooperative Group. AB - Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma. In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% Cl:1.09-2.06) for regular sunscreens, and of 2.28 (95% Cl: 1.28-4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% Cl: 1.25 15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens. PMID- 7790108 TI - Trends in incidence of testicular cancer in boys and adolescent men. AB - Several epidemiological studies have described increasing trends over time in the incidence of testicular cancer in adult men. Less attention has been given to the trends in young boys, adolescents and old men. This paper describes the incidence of testicular cancer in young boys (0-4 years) and adolescents (15-19 years) in Denmark, Norway and Sweden, and compares these trends with the corresponding data on adults. Although only small numbers were available, the data suggest that the incidence of testicular cancer in young boys has been constant, at a level around 0.5 per 100,000. This observation lends support to the idea that testicular cancer in young boys is aetiologically distinct from testicular cancer in adults. In all three populations we found a particularly high average annual increase in the incidence of testicular cancer in adolescents (around 6% per year). It is proposed that this increase is mainly caused by a secular trend towards earlier age at puberty. PMID- 7790107 TI - High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes. AB - T-antigen (TAg) coding sequences specific for BK virus (BKV) were detected, by PCR amplification followed by Southern-blot hybridization, in a high percentage of human tumors and tumor-cell lines, as well as in normal tissues, by analysis of 189 specimens. Specifically, the BKV early region was detected in 85% of brain tumors and in all normal brain tissues, in 78% of osteosarcomas, in 38% of Ewing's tumors, in 40% of normal bone specimens and in 71% of normal peripheral blood cell samples. Wilms' tumor tissues used as a control were all negative for BKV sequences. RT-PCR analysis indicated that TAg coding sequences were expressed in specimens carrying BKV early region, ranging from 64% of the osteosarcomas to 100% of glioblastomas, Ewing's tumors, peripheral blood cells and normal bone. Moreover, DNA sequencing performed in 12 different positive samples revealed that the amplified PCR products are identical to the early-region sequence of wild type BKV. The role of BKV TAg and its possible mechanism of action in human tumorigenesis are discussed. PMID- 7790109 TI - Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. AB - T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16 associated zeta chain in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas. PMID- 7790110 TI - Risks of second primary malignancy in patients with cutaneous and ocular melanoma in Denmark, 1943-1989. AB - Risks of 2nd primary cancer were assessed in all patients with cutaneous melanoma (12,460) and all patients with ocular melanoma (2,018) incident in Denmark from 1943 to 1989 and followed for totals of 88,667 person-years and 16,045 person years, respectively. After cutaneous melanoma, 972 2nd cancers occurred. The risk of non-melanoma skin cancer was significantly raised in each sex. Risk of all non skin cancers was not raised for all ages but was significantly increased for patients with the primary melanoma incident at ages under 50 years (standardised incidence ratio [SIR], i.e., ratio of observed to expected cancer incidence, multiplied by 100 = 117; 95% confidence interval [CI] 101-134). There were significantly increased risks of chronic lymphocytic leukaemia in males and both sexes combined, brain and nervous system cancers in females and both sexes combined and oropharyngeal cancer in both sexes combined. Risk of pancreatic cancer was not raised, suggesting that cutaneous melanoma patients generally do not share the diathesis for this malignancy which has been observed in certain families with atypical naevi and melanoma. There was no relation of 2nd primary cancer risks to duration since the first primary and no indication of any appreciable treatment-related risk. After ocular melanoma, 216 2nd cancers occurred. There was a significantly increased risk of 2nd cancer overall in males but not females and a significantly increased risk of liver cancer in each sex. Risk of non-melanoma skin cancer (NMSC) was not raised, which suggests that the aetiology of ocular melanoma is not mainly dependent on UV exposure, at least of the type causing NMSC. PMID- 7790111 TI - Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor infiltrating lymphocytes. AB - The progression of tumors such as renal cell carcinoma (RCC), despite the presence of substantial lymphocytic infiltrates (TIL), suggests that the ability of the local immune response to control tumor growth is impaired. Cytokine gene expression was examined to further investigate the nature of this response. Initial studies were performed with frozen tumors using PCR-assisted mRNA amplification with cytokine-specific primers for interleukin 10 (IL-10), interleukin 2 (IL-2) and interferon-gamma (IFN-gamma). IL-2 mRNA was not detected, despite the presence of T cells as defined by the expression of CD3 gamma mRNA. In contrast, mRNA for IFN-gamma was expressed in 4/9 and for IL-10 in 5/9 tumors. To confirm this, 5 fresh tumor specimens were examined, and PCR demonstrated that IL-10 mRNA was detectable in 4/5 tumors from which RNA was isolated at the time of nephrectomy. In these experiments multiple cycles and dilutions were employed to semi-quantitate the expression of IL-10. To identify potential sources of this cytokine in the tumor bed, IL-10 mRNA expression in freshly isolated lymphocytes and tumor cells, TIL lines, cultured RCC and established RCC lines was examined. Our studies demonstrate that within the tumor TIL may be one source of IL-10. Lymphocyte-enriched populations from 4/5 tumors expressed IL-10 mRNA as did 4/6 freshly isolated tumor cell preparations. IL-10 gene expression was not detected, however, in tumor cells after one passage in vitro in short-term cultured RCC tumor cells (passages 2-5) or in established RCC tumor cell lines. Finally, 4/9 CD4+ and 2/5 CD8+ TIL lines expressed IL-10 mRNA either constitutively or after stimulation with anti-CD3 antibody. This finding was associated with IL-10 production in vitro. Our studies demonstrate that IL-10 mRNA is frequently present in RCC tumors and may originate from the tumor infiltrating mononuclear cell population. PMID- 7790112 TI - Substance-P receptors in human primary neoplasms: tumoral and vascular localization. AB - Primary human neoplasms were examined for the presence of substance-P receptors by receptor autoradiography with 125I-labelled Bolton-Hunter substance P. Substance-P receptors were localized and characterized in the neoplastic cells of 9/12 astrocytomas, 10/10 glioblastomas, 10/12 medullary thyroid carcinomas, 8/16 breast carcinomas and 4/5 ganglioneuroblastomas. Conversely, substance-P receptors were not or only rarely identified on non-small-cell carcinomas of the lung (1/16), neuroblastomas (0/8), adenocarcinomas of the colon (1/21) or the pancreas (1/9), or on malignant lymphomas (3/18). However, in the great majority of the investigated tumours, substance-P receptors were found on intra- and peritumoral blood vessels. All substance-P receptors detected had the pharmacological characteristics of the neurokinin-I receptor sub-type. In addition, the expression of somatostatin receptors was examined in all the neoplastic tissues mentioned above. Both substance-P and somatostatin receptors were present in astrocytomas and in ganglioneuroblastomas, whereas little or no receptor was found in pancreatic and non-small-cell lung carcinomas. The extent of somatostatin-receptor expression was inversely correlated to that of the substance-P receptors in glioblastomas, neuroblastomas and non-Hodgkin's lymphomas. The tumoral and vascular localization of substance-P receptors in tumours may have clinical implications. The use of radiolabelled substance P for in vivo scintigraphy may supplement the current set of diagnostic tools. Substance-P antagonists might be used in the treatment of tumours, as their binding to vascular receptors may decrease tumoral blood supply and drainage. PMID- 7790113 TI - Cytogenetic findings in malignant peripheral nerve sheath tumors. AB - Clonal chromosome aberrations were detected in 8 short-term cultured malignant peripheral nerve sheath tumors (MPNST). Seven had a near-triploid chromosome number and I was in the hyperhaploid-hypodiploid range. No recurrent structural rearrangements were found; the bands most frequently involved (3 tumors) were 7p11, 12p13 and 14q11. The most common numerical changes were loss of a sex chromosome (all tumors) and loss of at least 1 copy of chromosomes 8, 16 and 22 (4 tumors). Pooling our data with those on the 20 previously published MPNST with abnormal karyotypes, we found that the chromosome number has often been in the triploid range (12 tumors), with stem line variation between 34 and 270. All chromosome arms, except 22p and the Y chromosome, were involved in recombinations. The most frequently rearranged bands were 7p22 (6 tumors) and 1p21, 7p11 and 14q11 (5 tumors each). Most numerical and unbalanced structural aberrations have led to loss of genetic material, in particular from Xq26-qter (13 tumors); 11q22-qter and 13p (12 tumors); 9p22-pter, 11p13-pter, 17p and 17q11 21 (11 tumors); 1p22-32 and 1p34-pter (10 tumors) and 6q25-qter and chromosome 16 (9 tumors). PMID- 7790114 TI - Inhibition of 3'-methyl-4-dimethylaminoazobenzene-induced hepatocarcinogenesis in rat by dietary beta-carotene: changes in hepatic anti-oxidant defense enzyme levels. AB - The dietary administration of beta-carotene (BC) daily has been found to be highly effective in reducing hepatocarcinogenesis in male Sprague-Dawley rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Met-DAB). The anti-cancer efficacy of BC was evaluated by estimating some possible pre-neoplastic and neoplastic hepatic anti-oxidant markers such as glutathione (GSH) and related enzymes, namely glutathione S-transferases (GSHT, with varying substrate specificities), gamma glutamyl transpeptidase (GGT), glutathione peroxidase (GPX) and reductase. BC proved to be an effective anti-neoplastic substance in long-term treatment. Furthermore, BC limited the exponential increase of GSH, GGT, GSH-T and GPX both in the hyperplastic nodules (HNs) and surrounding liver (NNSP) areas compared with carcinogen control (3'-Met-DAB) rats during long-term treatment. Early marginal changes in GSH, GGT and GSHT (with 1-chloro-2,4-dinitrobenzene as a substrate) activities in BC-treated groups for 10 days compared with carcinogen (3'-Met-DAB once) control rats entail the participation of BC in the initial stages of hepatocarcinogenesis. A decrease in the number of hyperplastic nodules and the total liver parenchyma they occupy was observed in BC-treated groups. HNs and NNSP liver areas are directly correlated with hepatic BC and vitamin A content and with rates and patterns of hepatic anti-oxidant defense enzymes. Our results confirm that BC is protective in limiting the action of 3'-Met-DAB during the initiation phase of hepatocarcinogenesis. PMID- 7790115 TI - Vitamin-D3 derivatives and breast-tumor cell growth: effect on intracellular calcium and apoptosis. AB - Vitamin-D3 derivatives are now well-recognized growth inhibitors of numerous tumoral cells and in particular breast-cancer cells. However, the mechanisms by which they operate are not well established. Among the wide range of physiological and biological functions of vitamin-D3 derivatives, the best described include their action on calcium homeostasis. In this study, we sought to establish whether the effects of vitamin-D3 derivatives on breast-cancer cell growth may be in part related to intracellular calcium modulation and induction of apoptosis. To address these questions, we used, in addition to 1,25(OH)2D3, the active metabolite of vitamin D3, a non-calcemic 1,25(OH)2D3 derivative: Ro 23 7553 [16-ene-23-yne-1,25(OH)2D3], which in our hands was more potent than the parent compound in inhibiting breast-cancer cell growth. We showed that the efficiency of both compounds in growth inhibition was higher in the estradiol receptor-positive-breast-tumor MCF-7 cells than in the estradiol-receptor negative MDA-MB 231 cells. In MCF-7 cells in particular, important modifications of intracellular calcium related to the emptying of intracellular pools were observed. The depletion of Ca++ from intracellular stores was followed by the induction of apoptosis. Such a phenomenon was never observed in MDA-MB 231 cells. Our results suggest that the action of vitamin-D3 derivatives on the depletion of calcium stores, which was more significant in MCF-7 than in MDA-MB 231 cells, may induce apoptosis in the former cells and account for the high efficiency of vitamin-D3 derivatives on growth inhibition of MCF-7 breast-tumor cells. PMID- 7790116 TI - Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody redirected T cells in an immunocompetent rat model. AB - Effectiveness of bispecific-monoclonal-antibody (BsMAb)-mediated cellular anti tumour activity was evaluated in vitro and in vivo in relation to the additional need for T-cell activation in a new immunocompetent rat tumour model. L37 tumour cells, derived from a squamous-cell carcinoma of the lung of Wag/Rij rats, were transfected with the cDNA coding for the human 38-kDa transmembrane pan-carcinoma associated antigen EGP-2. Intravenous inoculation of EGP-2-positive L37 cells resulted in a rapid outgrowth of EGP-2-positive tumour nodules in the lungs. A BsMAb BIS-19, recognizing EGP-2 on the transfected tumour cells and the T-cell receptor of the rat, was made and allowed specific lysis of EGP-2-transfected L37 tumour cells by activated rat T lymphocytes in vitro. In vivo T-cell activation, assessed by up-regulation of IL-2-receptor expression, could be induced by daily injection of rat rIL-2. Intravenous treatment of tumour-bearing EGP-2-positive L37 tumour with BIS-19 together with rat rIL-2 resulted in almost complete disappearance of established tumour. In contrast, animals treated with BIS-19 alone, IL-2 alone or a combination of anti-EGP-2, anti-TcR and IL-2 showed much less or no tumour reduction. These results show effectiveness of systemic treatment with BsMAbs to induce anti-tumour activity in established tumours. Immune activation prior to or during treatment with BsMAbs, as achieved with IL 2, appears to be a prerequisite for successful treatment. PMID- 7790117 TI - Integrin expression on colorectal tumor cells growing as monolayers, as multicellular tumor spheroids, or in nude mice. AB - In this study we compared the expression of integrin alpha chains 2, 3, 4, 5, 6, v and the beta chains 1, 3, 4 in 2 colorectal carcinoma cell lines (HRT-18 and CX 2), growing in confluent and subconfluent monolayer cultures, as multicellular tumor spheroids and in nude mice, using the immunofluorescence technique (confocal microscopy) and flow cytometry. The fast-growing cell line HRT-18 expressed, in confluent and subconfluent monolayer cultures, alpha 2, 3 and beta 1 with a continuous membranous staining pattern, whereas alpha v, alpha 6, and beta 4 were expressed continuously membranous in the intermediate and apical part of the cell layer, and clustered at focal contacts at the base of the cells. In spheroids and tumors of nude mice the focal pattern of alpha v, 6 and beta 4 was changed into a diffuse one. Using flow cytometry, the expression of alpha 3 was found to be reduced in spheroids of HRT-18. The slowly-growing cell line CX-2 expressed, under the same conditions in monolayer culture, alpha 6, beta 1 and beta 4, and very weakly alpha 2, 3, 5 and v. Alpha 3 was expressed in spheroids of CX-2 only at the outer rim where the cells proliferate. In contrast, alpha 2 and 5 were expressed mainly in the quiescent, non-proliferating area. Alpha 6 was reduced in spheroids of CX-2. In the nude mouse tumor of CX-2, alpha 5 was expressed only focally and very weakly, alpha 2 was no longer detectable, but alpha v appeared to be enhanced in a focal pattern. These data indicate that integrin expression of tumor cells depends upon the culture system and that integrin expression in multicellular tumor spheroids is more similar to the in vivo situation in nude mouse tumors. PMID- 7790118 TI - Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern. AB - In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival. PMID- 7790119 TI - Gene transfer of human TNF alpha into glioblastoma cells permits modulation of mdr1 expression and potentiation of chemosensitivity. AB - Despite substantial advances in the surgery, radiotherapy and chemotherapy of gliomas, the prognosis of patients with glioblastomas has still not improved. Disappointing results in chemotherapy of glioblastomas resulting from multi-drug resistance (MDR) prompted us to investigate the influence of cytokine gene transfer in glioblastoma cells on the expression of P-glycoprotein and on chemosensitivity of transduced cells. Several investigations have shown that malignant gliomas express P-glycoprotein at high levels. The P-glycoprotein is a product of the multi-drug resistance gene (mdr1) and functions as an energy dependent efflux pump which decreases drug accumulation and cytotoxicity. Since tumour necrosis factor alpha (TNF alpha) is a powerful anti-cancer agent used in clinical trials and gene therapy protocols, this cytokine gene was chosen for the present investigations. Transduction of the human TNF alpha (hTNF) gene carrying retroviral vector pN2tk-hTNF into U373MG human glioblastoma cells resulted in expression and secretion of biologically active hTNF. Release of transduced hTNF reduces P-glycoprotein expression and is associated with enhanced rhodamine-123 uptake and potentiation of cytotoxicity of the MDR-relevant drugs vincristine and doxorubicin. Furthermore, the transfected cell clones showed a reduced growth rate compared to the parental cells. PMID- 7790120 TI - Suramin sodium: pronounced effects on methotrexate transport and anti-folate activity in cultured tumor cells. AB - Suramin is an experimental anti-neoplastic agent which has shown promising activity against prostatic carcinoma and lymphoma in clinical trials. To elucidate its mechanism of action, suramin was examined for an effect on the transport of folate compounds by tumor cells. Influx of the anti-folate methotrexate via the reduced-folate carrier system of CCRF-CEM cells was found to be highly sensitive to inhibition by suramin but not to various other arylsulfonic acids. Inhibition by suramin was competitive, and the inhibition constant Ki was 1.3 microM, a value 3-fold lower than the Kt for half-maximal influx of methotrexate. Folate binding to the membrane-associated folate-binding protein of KB cells was not affected by suramin. Growth studies revealed that the response of human CCRF-CEM, KB, PC-3 and MCF-7 cells to methotrexate was antagonized from 6- to 17-fold by pharmacological levels (10-200 microM) of suramin. Conversely, growth inhibition was additive or synergistic when suramin was combined with metoprine, a lipophilic anti-folate which enters cells by diffusion. Synergism was observed between metoprine and suramin in CCRF-CEM cells, which take up folate exclusively through the reduced-folate carrier (inhibitable by suramin), whereas additivity was observed for KB cells, which rely largely on the folate-binding protein (unaffected by suramin) for folate import. Our results indicate that inhibition of cellular transport of folate compounds may explain part of the anti-neoplastic effects of suramin on tumor cells. PMID- 7790121 TI - Colon goblet cells lose proliferative response to TGF alpha as they differentiate. AB - Two cell line models for colon goblet cells expressed 6- to 14-fold elevated levels of the EGF receptor, 3- to 5-fold levels of TGF alpha and 11- to 15-fold levels of amphiregulin compared with 2 cell lines which model colon enterocytic differentiation, suggesting a role for the EGF receptor and its ligands in goblet cell growth control. Two HT29 colon carcinoma sublines were used to model normal goblet cells at different stages of maturation. TGF alpha induced a 2-fold increase in growth of the HD8 subline but inhibited the growth of the more differentiated HD6 subline by 40%. EGF receptors were activated in each line by ligand, but signal transduction varied sharply. Both MAP kinase isoforms, p44 and p42, were markedly activated in HD8 cells for at least 20 min, while only a marginal activation was seen in HD6 cells. In contrast, the more differentiated HD6 cells showed an increase in 105 kDa MBP kinase activity with EGF treatment, while HD8 cells displayed constitutively elevated levels of this kinase. Thus, activated EGF receptors initiated different signalling pathways in model cell lines for colon goblet cells at different stages of maturation. TGF alpha protein levels have been shown by other investigators to be restricted to the top of the cylinder-like colonic crypt, where cells terminally differentiate and cease division, an unexpected location for an epithelial cell mitogen. Our data with model cell lines imply that normal colon goblet cells lose proliferative response to TGF alpha as they differentiate and the elevated levels of TGF alpha at the top of the colonic crypt in vivo serve to inhibit goblet cell growth. PMID- 7790122 TI - Susceptibility of colorectal-carcinoma cells to natural-killer-mediated lysis: relationship to CEA expression and degree of differentiation. AB - This study addresses the relevance of colorectal-carcinoma-cell (CRC) CEA expression and degree of differentiation in natural-killer(NK)-mediated lysis susceptibility. A 51Cr-release cytotoxicity assay performed with 5 human CRC lines demonstrated that CRC CEA expression was related to resistance to NK lysis. Moreover, the addition of anti-CEA Fab fragments to the assay led to a significant increase of lysability of high-CEA-producing and NK-resistant cells (LS 174-T), whereas purified CEA drastically reduced lysis of low-CEA-producing and NK-susceptible cells (LISP-I) in a dose-dependent manner. These results strongly suggest that CEA plays a causal role in CRC resistance to NK lysis. Nevertheless, our data did not demonstrate CEA binding to effector cell surface, suggesting that CEA expression can protect CRC, possibly by preventing NK-tumor cell adhesion to occur. Our results also show that CRC susceptibility to NK lysis was related to a less differentiated phenotype. HCT-8, which are poorly differentiated and low-CEA-producing cells, were cultured in vitro in the presence of the differentiation agent sodium butyrate. Treated cells became less susceptible to NK lysis as they progressed towards a more differentiated phenotype. However, CEA production was not altered upon differentiation. Our study thus demonstrates that both features, CEA expression and degree of cellular differentiation, may individually influence CRC susceptibility to NK lysis. PMID- 7790123 TI - Natural killer (NK) cells as effectors of antibody-dependent cytotoxicity with chimeric antibodies reactive with human squamous-cell carcinomas of the head and neck. AB - In patients with cancer, antibody-dependent cellular cytotoxicity (ADCC) may be used as a laboratory test or for enhancing immunotherapy with murine monoclonal or chimeric mouse/human anti-tumor antibodies (mMAbs or cMAbs, respectively). We have established an ADCC assay with IgG1 cMAb SF-25, using human squamous-cell carcinoma of the head and neck (SCCHN) cell lines as targets. By flow cytometry, all SCCHN cell lines tested expressed the antigen recognized by cMAb SF-25. Trypsinization of the cell monolayers facilitated binding of cMAb SF-25 to the antigen on the cell surface of SCCHN targets. Using the PCI-50 SCCHN cell line as a target coated with this cMAb at the optimal concentration of 1.0 micrograms/ml, normal human peripheral blood mononuclear cells (PBMC, n = 28) were found to mediate ADCC at a mean level of 283 +/- 42 (SEM) lytic units (LU20/10(7) effector cells). Non-adherent monocyte-depleted PBMC and natural killer (NK) cells purified by negative selection mediated significantly higher levels of ADCC than unseparated PBMC against SCCHN targets. NK cells, defined as CD3-CD56+ cells, could be effectively armed by cMAb SF-25, as confirmed by flow cytometry and ADCC assays. IL2-activated armed NK cells mediated higher levels of ADCC than non armed NK cells. Binding of cMAb SF-25 to NK cells and their ADCC were enhanced by pre-incubation with polyethylene glycol. Arming of NK cells with chimeric antibodies should be considered in developing novel strategies for treatment of human SCCHN, especially in the adjuvant setting. PMID- 7790124 TI - Circumvention of confluence-dependent resistance in a human multi-drug-resistant colon-cancer cell line. AB - Colorectal adenocarcinomas are inherently resistant to anthracyclines and other topoisomerase-II inhibitors. Resistance to doxorubicin of colon cancer cells (Caco2) depends on 2 main mechanisms. The first is typical multi-drug resistance, characterized by the mdr1 gene and its product the P170 membrane glycoprotein. P170 effluxes anthracyclines out of cancer cells and is antagonized in vitro by verapamil. The second mechanism, which develops when cell-culture density increases, we have designated confluence-dependent resistance. Confluence dependent resistance depends on the reduced topoisomerase II content of the G0/G1 phase cells which accumulate in the confluent population. We show here that short treatments of confluent Caco2 cells with slightly toxic concentrations of DNA damaging agents (cisplatin, melphalan or mitomycin C) produced a transient accumulation of cells in S- and G2/M-phases of the cell cycle. Concomitantly with the increase in the S-phase population, the topoisomerase II cellular level and the sensitivity of cells to doxorubicin were greatly enhanced. Overcoming confluence-dependent resistance through S-phase accumulation and inhibition of multi-drug resistance by verapamil were fully additive, and a nearly complete reversal of confluent Caco2 cells' resistance to doxorubicin was obtained when both strategies were combined. PMID- 7790125 TI - Correlation between functional and molecular analysis of mdr1 P-glycoprotein in human solid-tumor xenografts. AB - The contribution of P-glycoprotein (Pgp) to multidrug resistance in human solid tumors is generally estimated from bulk mRNA measurements or immunohistochemistry, while direct measurement of the effect of Pgp on intracellular drug concentrations has not been pursued. We investigated the feasibility and sensitivity of a method for probing Pgp-mediated drug transport in cells isolated from solid tumors, using xenograft models. Human tumor xenografts (XG) were grown by s.c. injection of Pgp-expressing cell lines 2780AD, BRO/mdr1 and KB8-5. Tumor uptake of doxorubicin (DOX) after administration of DOX to the mice was determined. XG from untreated mice were enzymatically dissociated. The effect of the Pgp modulator bepridil on steady-state cellular daunorubicin (DNR) and vincristine (VCR) accumulation and chemosensitivity of these XG cells was compared with its effects in the cell lines (CL). mdr1 mRNA and Pgp (by flow cytometry) were measured. Also, the dependence on intracellular ATP concentration, [ATP]i, of the modulator effect was determined in intact KB8-5 cells. The results showed that i.v. administration of DOX to the mice led to lower DOX levels in the Pgp-expressing XG than in the "sensitive" XG, suggesting the presence of an in vivo functional Pgp in these XG tumor models. Dissociated, viable XG cells appeared to have ATP levels sufficient to sustain Pgp-ATPase coupled drug transport. This was inferred from experiments using KB8-5 CL, which showed half-maximal inhibition of DNR transport at an [ATP]i of 1 to 2 mM. The effect of bepridil on DNR and VCR accumulation and chemosensitivity in the XG cells was in accordance with the XG expression of mdr1/Pgp. In KB8-5 XG cells, Pgp function was hardly detectable, in accordance with decreased mdr1/Pgp expression in vivo. In conclusion, Pgp activity can be determined in freshly dissociated XG human tumor cells. The results obtained with the more necrotic KB8 5 XG may represent some of the interpretation problems arising when low levels of Pgp expression occur within a heterogeneous cell population, such as may be expected in clinical human tumors. Also our results indicate that Pgp activity may be impaired in vivo at [ATP]i below 2 mM, which are realistic values for human solid tumors. PMID- 7790126 TI - Alcohol, tobacco, illicit drugs, and sex: an analysis of risky behaviors among young adults. AB - This paper reexamines data from two previous surveys. It looks at self-reported alcohol, tobacco, and illicit drug use and sexual risk-taking among three subgroups of young adults. All subjects (N = 1,387) were aged 20-30. The samples consisted of nurses in the Lothian Region, and residents in Muirhouse (Edinburgh) and Easterhouse (Glasgow). Factor analysis revealed that risk-taking behavior was neither entirely general nor entirely specific. Although there was some tendency for a risk-taker in one area to be a risk-taker in others, five fairly distinct types of risk-taking could be distinguished. These included sexual risk-taking, illicit use of drugs, and excessive alcohol consumption. The samples differed in the extent to which they indulged in the different types of risk-taking, and various other predictors of these behaviors were found. Different patterns of association emerged in relation to specific subgroups of respondents. PMID- 7790128 TI - A comparison of pathological gamblers to alcoholics and cocaine misusers on impulsivity, sensation seeking, and craving. AB - Consecutive admissions (N = 843) to the Brecksville Veterans Addiction Recovery Center with a primary diagnosis of pathological gambler, alcoholic, or cocaine misuser were compared for differences on impulsivity, sensation seeking, and craving. In contrast to alcoholics and cocaine misusers, gamblers scored significantly higher on impulsivity and inability to resist craving; however, gamblers were not significantly higher than either alcoholics or cocaine misusers on sensation seeking. These findings suggest a need to address high impulsivity and inability to resist cravings in treatment and relapse prevention for gamblers. PMID- 7790127 TI - Evaluation of an AIDS education model for women drug users in jail. AB - This paper reports outcome evaluation results of an AIDS education program for drug-using women in jail, of whom the majority were current drug injectors, had high-risk sexual partners, and never used condoms for insertive sex. The women participated in four small-group health/HIV education sessions. Education participants and controls were followed-up 7 months after their release from jail; the two groups did not differ significantly on drug- or sex-related HIV risk behaviors at follow-up. However, being in drug dependency treatment (primarily methadone maintenance) at follow-up was associated with reduced heroin use, crack use, drug dealing, and criminal activity. Although improved HIV education in jail is important, better networks of community resources, including more accessible community drug dependency treatment, also must be developed to support drug-dependent women after their release from jail. PMID- 7790130 TI - Intentions to share injection paraphernalia: an empirical test of the AIDS Risk Reduction Model among injection drug users. AB - The AIDS Risk Reduction Model is a theory-based representation of sequential psychosocial processes by which people may attempt to change their HIV risk behavior. These processes are said to occur in three stages: 1) labeling one's risk behavior as problematic, 2) forming an intention to change behavior, and 3) taking action to accomplish change. Cognitive and perceptual factors are said to influence progress across stages. This study tests the degree to which hypothesized relationships among factors at Stages 1 and 2 are consistent with cross-sectional data collected from a sample of HIV-negative injection drug users who reported recent sharing of drug injection paraphernalia ("works"). Findings indicate that intentions to share works less often in the future may be influenced directly by drug users' perceived risk of infection, which in turn is influenced by their level of HIV knowledge, perceived susceptibility to HIV, and perceived peer norms regarding drug-related risk reduction. PMID- 7790129 TI - Drug use in Hungary: an overview. AB - Based on surveys and clinical data, it is concluded that the use of illegal drugs is spreading in Hungary. The social composition of drug users is changing and new forms of drugs and uses have appeared, such as heroin use and cocaine snorting. The legal regulation of access to drugs changed in 1993: stricter sentences can be imposed on drug traffickers, while the possibility has been created for drug users to undertake therapy in place of punishment. The Interministerial Committee on Drug Affairs and the Hungarian Association on Drug Use and Addiction have been set up. There are a few scientifically-based prevention programs. A number of clear paradigms have emerged in prevention policy and therapy, although it is not yet possible to see which of these will be confirmed by time and practice. PMID- 7790132 TI - Depression and relapses in treated chronic alcoholics. AB - In a sample of 99 male alcoholics at an alcoholics' rehabilitation clinic we recorded drinking/abstinence behavior and depression up to 1 year after discharge. Seventy-eight patients completed the inpatient therapy, and of these, 39 respondents were recorded up to the final follow-up point. Generally, the initial, markedly elevated depression scores had declined significantly by the end of the inpatient treatment. In the abstainers, the depression scores continued to fall after release and remained low throughout the entire observation period. In patients who resumed alcohol use, relapses were accompanied by immediate, sharp increases in the scores, but declined upon a return to abstinence. PMID- 7790133 TI - Evolution of drug consumption in a sample of adolescents: the predictive capacity of the genesis model. AB - This paper analyzes the predictive capacity of the genesis model for drug consumption constructed by the authors in an attempt to identify the characteristics of a drug consumption risk population. Several years' research have shown the model's validity in explaining drug consumption, a behavior understood as one of the many for possible use by adolescents to adapt to the environment in which they develop. The potential for behavior which deviates from the norm depends on a variety of factors considered in the model (including level of self-control, attitudes to drugs, or the existence of peers to reinforce such behavior). The predictive capacity of the model is analyzed in a longitudinal study carried out on a sample of 476 students (238 men and 238 women). PMID- 7790131 TI - Tension-reduction expectancies and alcoholic beverage preferences revisited: associations to drinking frequency and gender. AB - The relationships among drinking frequency, gender, beverage preference, and tension-reduction outcome expectancies were examined. Subjects consisted of 503 social-drinking college undergraduates. Results indicated that regardless of preferred beverage type, "high" versus "low" frequency drinkers endorsed significantly greater tension-reduction expectancies. Results also indicated that males and "frequent" drinkers preferred beer as their primary alcoholic beverage. Supplemental analyses suggested that drinking frequency partially confounded the relationship between gender and beverage preference. These results extend and refine previous research and have implications for alcohol misuse prevention and early intervention. PMID- 7790134 TI - Women in dermatology: gender and tropical diseases. PMID- 7790135 TI - Acne rosacea and Helicobacter pylori betrothed. PMID- 7790136 TI - The exanthem of HIV-1 seroconversion syndrome. PMID- 7790138 TI - Co-morbidity between dermatologic diseases and psychiatric disorders in Papua New Guinea. AB - BACKGROUND: Neurodermatitis (now subdivided into lichen simplex chronicus and atopic dermatitis) was included among the psychosomatic disorders. Psychologic causes have been suggested for many skin conditions, such as urticaria, lichen simplex chronicus, atopic dermatitis, psoriasis, alopecia areata, and pruritus. The evidence for psychologic causation is neither strong nor convincing; however, psychiatric disorders are common among people with established skin diseases. Recent investigators have published data reporting co-morbidity between certain psychiatric disorders and skin diseases. The objective of the research was a prospective clinical study of 132 consecutive patients, who attended the dermatologic outpatient clinic of the Port Moresby General Hospital during 1992. METHODS: The instrument for the study is the "Harding Self-Rating Questionnaire (SRQ) that has been demonstrated to work well as a gross screening instrument in the Urban Primary Health Care Clinic setting. The questionnaire was administered to 132 outpatients by one of the investigators (HM). Those patients who scored above the cut-off point of seven were referred to the second investigator (FYAJ) for examination of their mental state. RESULTS: The results of the study showed all 132 patients were adults, aged between 16 and 75 years. There were 67/132 (50.75%) men and 65/132 (49.24%) women patients. The psychiatric diagnoses for the women patients were: normal variation 17/65, anxiety neurosis 11/65, and neurotic depression 37/65. For the men patients, the psychiatric diagnoses were: normal variation 21/67, anxiety neurosis 15/67, and neurotic depression 30/67. One man with psoriasis also presented with clinical features of schizophrenic psychosis. CONCLUSIONS: The results of the study support the hypothesis, that there is a co-morbidity between some psychiatric disorders and some skin diseases. PMID- 7790137 TI - Secondary syphilis: a clinicopathologic study. AB - BACKGROUND: With the resurgence of syphilis in the HIV era, a greater awareness of the clinicopathologic features of the disease is desirable. This report describes and correlates the clinical and histopathologic features of secondary syphilis seen at a teaching hospital in Delhi, India. METHODS: Forty biopsies of mucocutaneous lesions from 31 consecutive patients with secondary syphilis, seen between September 1987 and January 1991, were studied and the histopathologic findings correlated with the clinical findings. RESULTS: A spectrum of histopathologic changes ranging from a minimal infiltrate to granulomatous inflammation throughout the dermis was seen. The pattern of inflammation correlated well with the type of skin lesion, with macules showing the least and nodules the most prominent changes. The predominant cell type in the infiltrate was the mononuclear cell/lymphocyte. Plasma cells were seen infrequently except in condylomata lata. Endothelial proliferation, the "classical" feature of the histopathology of syphilis was noted infrequently. CONCLUSIONS: The histologic manifestations of secondary syphilis appear to be as varied as the clinical ones. This calls for close interaction between the clinician and the pathologist to correlate the clinical, serologic, and histologic findings to establish the diagnosis of syphilis. PMID- 7790140 TI - Dermatofibrosarcoma protuberans. AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant tumor of the skin, the diagnosis of which can be difficult not only clinically but also histologically. The tumor has a low metastatic potential, but tends to recur locally if removal is incomplete. METHODS: We reviewed the clinical and histologic features of 19 cases of DFSP, seen at the Department of Dermatology (14 cases) and Department of Surgery (5 cases) at the Hull Royal Infirmary between 1975 and 1992. RESULTS: There were only 19 cases of DFSP diagnosed from a population of 500,000 over a period of 17 years. None of the cases were diagnosed clinically prior to histologic diagnosis. The highest incidence was in the 4th decade of age. The most frequent site was on the head and neck. None of the lesions metastasized but there were a total of eight incidents of local recurrence in five patients. Histologically all the cases showed presence of storiform-pattern spindle-shaped cells and new collagen formation. CONCLUSIONS: Dermatofibrosarcoma protuberans is a soft tissue tumor that is often not recognized clinically due to its rarity and variable appearance. Local recurrence is frequent. A wide surgical excision is the treatment of choice. PMID- 7790139 TI - Mucocutaneous manifestations of lymphomas and leukemias in black Kenyan children. AB - BACKGROUND: Childhood leukemia and lymphoma are common problems in Tropical Africa, including Kenya. Studies done in Western populations indicate that 25-50% of patients with leukemia and lymphoma have specific or nonspecific cutaneous signs. In dark-skinned patients, reports of such mucocutaneous manifestations are scarce. The lesions in these patients may easily be missed, if not specifically looked for. METHOD: Eighty-six indigenous Kenyan children with a confirmed diagnosis of leukemia or lymphoma were specifically examined for any mucocutaneous manifestations at presentation, during their treatment, and during subsequent follow-up. Whenever possible, an attempt was made to determine the causes of these lesions. All patients were given standard therapy for the primary hematologic disorder. RESULTS: Two-thirds of the patients had mucocutaneous symptomatology at presentation: 17.4% had skin infiltration by the malignant cells. During therapy an even larger number developed nonspecific skin manifestations. Most of these were the result of myelosuppression, immunosuppression, or direct cytotoxic effects on tissues. CONCLUSIONS: Mucocutaneous manifestations in black children with leukemia and lymphoma are very common. PMID- 7790141 TI - Cutaneous endometriosis. PMID- 7790142 TI - Drug-induced acute generalized exanthematous pustulosis with positive patch tests. PMID- 7790143 TI - Angiolymphoid hyperplasia with eosinophilia in a Filipino man. PMID- 7790144 TI - Malignant eccrine acrospiroma of the breast. PMID- 7790145 TI - Subcutaneous dirofilariasis caused by Dirofilaria (nochtiella) repens in a Belgian patient. PMID- 7790146 TI - Antidermatophytic activity of garlic (Allium sativum) in vitro. AB - BACKGROUND: Interest in herbal medicine is enjoying a renaissance at present. Garlic (Allium sativum) is an intriguing herb with a long history of medicinal use for a variety of diseases including ringworm infections. METHODS: Antidermatophytic activity of the aqueous extract of garlic (A. sativum) was investigated against 88 clinical isolates of dermatophytes by an agar dilution technique. The isolates included Microsporum canis (50), M. audouinii (5), Trichophyton rubrum (6), T. mentagrophytes (5), T. violaceum (12), T. simii (5), T. verrucosum (1), T. erinacei (1), and Epidermophyton floccosum (2). The results were compared with the minimal inhibitory concentrations of ketoconazole. RESULTS: The aqueous extract of garlic, diluted 1:150 and 1:100, had inhibited 50 and 90% of the isolates tested, whereas the respective values for ketoconazole were 1 and 2.5 micrograms/mL. CONCLUSIONS: Garlic (A. sativum) could be used as an effective antidermatophytic agent. Further purification and extraction of the active principle of garlic would give a true antidermatophytic activity comparable to standard antifungal drugs. PMID- 7790147 TI - Effect of orally administered antithyroid thioureylenes on PCNA and P53 expression in psoriatic lesions. AB - BACKGROUND: Antithyroid thioureylenes are effective agents in the oral and topical treatment of patients with chronic plaque psoriasis. METHOD: The effect of oral treatment with 6-n-propyl 2-thiouracil (propylthiouracil, PTU) and 2 mercapto 1-methyl imidazole (methimazole, MMI) on proliferating cell nuclear antigen (PCNA), and p53 protein expression was studied in patients with stable plaque psoriasis. RESULTS: Following treatment with PTU and MMI, PCNA staining in psoriatic epidermis was significantly decreased. P53 was minimally expressed in untreated lesions, and treatment with PTU and MMI did not enhance p53 expression in the psoriatic lesions. CONCLUSIONS: Since PCNA is a marker of cellular proliferation and p53 inhibits cellular cycling, some of the beneficial effects of PTU and MMI in psoriasis may depend on the ability of the drugs to impair cellular turnover, perhaps by binding to the triiodothyronine (T3) receptor. These effects may be in addition to the previously described effects of PTU and MMI as immune modulators and free radical scavengers. PMID- 7790148 TI - Cutaneous fungal infections: innovative treatment schedules with systemic agents. PMID- 7790149 TI - Oh what a tangled web: the medicinal uses of spider silk. PMID- 7790150 TI - Epidermal growth factor and epidermal growth factor receptor in umbilical metastasis from scirrhous carcinoma of the stomach. PMID- 7790151 TI - Treatment of cutaneous leishmaniasis with oral itraconazole. PMID- 7790152 TI - Umbilicated lesions in leprosy. PMID- 7790153 TI - The teaching/learning preferences of student nurses in the Republic of Ireland; background issues and a study. AB - Teaching and learning in all forms of education is being increasingly reviewed in a climate of educational accountability. The literature generally displays a certain irrationality about nurse education; on the one hand teachers are espousing student-centred ideologies while on the other hand, students are expressing preferences for teacher-structured approaches. The research on nurse education generally concludes that the roles of teacher and student operate around a mechanistic view of man with the teacher being viewed as the front of all knowledge and the students the passive recipients of that which was given. This paper reports on related background issues, and a study of the teaching/learning preferences of student nurses from general, psychiatric, sick children's and mental handicap nursing. Whilst students reflected preferences for more teacher-structured strategies, significant differences were identified between the preferences of the four groups of student nurses. It is concluded that any insistence on a doctrinaire approach to teaching and learning would be unnecessarily restrictive to the whole process of nurse education. Nurse tutors therefore need to reflect on what they do, particularly that which influences the relationship between the students and what they learn. It is then the responsibility of nurse tutors to act on what they have learned about that relationship and their part in it. PMID- 7790154 TI - Is there a physiological basis for the couvade and onset of paternal care? AB - Couvade is the male experience of pregnancy and couvade syndrome incorporates a range of symptoms suffered by "pregnant" men. The aetiology of the couvade syndrome is unknown. Anthropologists, psychiatrists, nurses and sociologists have provided explanations for behaviour changes in "pregnant" men in terms of cultural pressure, intrapsychic processes and psychosocial adaptation to a new situation. The adoption of a biological perspective allows us to ask a new question: is there a physiological basis for the couvade syndrome? A fresh research agenda would include measurement of physiological change and a search for causation. Implications for nursing are outlined. PMID- 7790155 TI - Agency registered nurse use of medical equipment: an Australian perspective. AB - This cross-sectional survey explored how and what 142 registered nurses working for a nursing agency in a large South Australian city initially learn about the medical devices they use in direct patient care, as well as the consequences of device use both for patients and staff. The most frequently identified method of initial learning was reading the user/instruction manual. Furthermore, 87.1% of respondents indicated they had received instruction from another staff member on their units, typically another registered nurse. At least 90% of participants indicated they initially learned the purpose of the device and how to operate it. Medical device use caused 39.4% of registered nurses to feel stress. Only 10% indicated that they had used a medical device that had harmed a patient. PMID- 7790156 TI - Evaluating quality nursing care through peer review and reflection; the findings of a qualitative study. AB - The purpose of this study was to examine the everyday methods by which nurses evaluate quality care. The method was qualitative; specifically, a grounded theory approach was used. The sample comprised 18 registered nurses from a large hospital in the south of England. Data was collected through tape recorded interviews and the constant comparative method used to analyze the data. The findings revealed that although nurses used objective methods such as evaluating planned care as part of the nursing process, they also used more subjective methods such as peer review and intuition. The study seeks to explain the value of these less formal methods of evaluation and recognises how difficult they may be to substantiate in light of the recent health care reforms. It is suggested that the use of a more formalised process of peer review using reflection as its foundation would enable nurses to satisfy managerial concerns for a measurable outcome to quality. PMID- 7790157 TI - Conditions, interventions, and outcomes in nursing research: a comparative analysis of North American and European/International journals. (1981-1990). AB - This study compared the conceptual foci and methodological characteristics of research projects which tested the effects of nursing interventions, published in four general nursing research journals with predominantly North American, and two with predominantly European/International authorship and readership. Dimensions and variables of comparison included: nature of subjects, design issues, statistical methodology, statistical power, and types of interventions and outcomes. Although some differences emerged, the most striking and consistent finding was that there were no statistically significant differences (and thus similarities) in the content foci and methodological parameters of the intervention studies published in both groups of journals. We conclude that European/International and North American nursing intervention studies, as reported in major general nursing research journals, are highly similar in the parameters studied, yet in need of overall improvement. Certainly, there is no empirical support for the common (explicit or implicit) ethnocentric American bias that leadership in nursing intervention research resides with and in the United States of America. PMID- 7790158 TI - Survey and critique of studies related to shift length variations in nursing from 1970 to 1993. AB - The purpose of this study was to describe the current status, stage of staffing change, and findings of research relating to shift length variations in nursing. This was accomplished through a review of the literature to (a) evaluate the quality of the research, (b) summarize and draw conclusions related to variations in nursing shift length, and (c) identify gaps in the literature for the purpose of making recommendations for future studies related to nursing shift length variations. Multiple methods were utilized for locating potential studies to include in this project. Smith and Stullenbarger's (1991) Quality of Study instrument was used to rate the studies. None of the research reviewed explicitly identified a conceptual or theoretical framework or model, and few studies could be classified as scientifically rigorous. This study illuminates the state of the art and findings related to length of shift variations in nursing, and as such has implications for practice and research in nursing service administration. PMID- 7790159 TI - A model for counterparts in international nursing. AB - The concept of counterpart is used by international health agencies to achieve the transfer of skills necessary for the ongoing viability of international nursing programs. The goal of the counterpart relationship is for the host group counterpart to assume responsibility for the project. The counterpart relationship is seen as a spectrum across which knowledge is transferred from counterpart to counterpart. Where each counterpart relationship falls on the spectrum depends on the degree of knowledge each brings to the relationship and changes across the life of the project. The tasks each counterpart must accomplish to ensure a successful relationship are illustrated by a faculty preparation program developed in the People's Republic of China. PMID- 7790161 TI - On the general concepts of action and ability. A philosophical introduction to the theory of handicaps. AB - The main task of this paper is to contribute to the theory of disabilities and handicaps, in particular their characterization and classification. It presents an analysis of the conditions for the successful performance of actions. By this procedure a list of reasons for failure of action, i.e., for disability and handicap, is obtained. This list can be used for a detailed classification of disabilities and handicaps. Some theories in modern philosophical action theory serve as platforms for the analysis. PMID- 7790160 TI - Technology and disability. Assessment needs and potential. AB - In assessing technologies for disabled people, the aims of habilitative or rehabilitative interventions, the concepts of disability and handicap, and the potential of existing and emerging technologies in various social arenas, as well as the structure of service delivery systems, are of importance. A discussion of these issues in the light of previous work on cost and effectiveness in the field is given. PMID- 7790162 TI - An elemental resource for the human-task interface. AB - The elemental resource model (ERM) attempts to provide a quantitative and straightforward framework for characterizing the human system, tasks, and their interface. It evolved in large part from the general systems performance theory (GSPT), which was developed first and independently. Resource constructs are used exclusively for modeling the abstract idea of system performance and for subsequent measurement of performance resource capacities. Resource economic principles provide a cause-and-effect description of the human-task interface. While argued to have immediate utility, it also provides the motivation to consider coordinated, collaborative, long-term developments that could facilitate effective decision making and technology utilization in rehabilitation. PMID- 7790163 TI - National structures in the delivery of rehabilitation technology services. AB - The delivery of rehabilitation services requires an infrastructure if service provision is to be given any priority. This article discusses some characteristics of handicaps, technical aids, the service delivery process, and habilitation/rehabilitation, and recommends developments of national structures for service delivery based upon the characteristics of rehabilitation technology, user need, and the country frameworks. PMID- 7790164 TI - The potential of technological innovations for the disabled. AB - Technical innovations have enormous potential for enhancing the lives of people with disabilities, often providing means for substantial independence and contributing to their dignity. This paper uses a framework related to the personal needs of individuals throughout the hours of waking and rest. Examples of various potentialities are provided and discussed. PMID- 7790165 TI - Communication aids for the speech impaired. Cost and quality-of-life outcomes of assessment programs provided by specialist Communication Aids Centers in the United Kingdom. AB - An evaluation was conducted of the approaches, costs, and quality-of-life outcomes associated with communication aid assessment programs for the speech impaired provided by specialist Communication Aids Centres (CACs) in the United Kingdom. The average costs of CAC assessment programs was 410 pounds per client, which is not excessive. There was evidence of moderate quality-of-life benefits from clients' use of the recommended aids. PMID- 7790166 TI - Orthoses and prostheses. AB - Orthoses and prostheses include a wide range of devices and strategies for correcting and alleviating dysfunction and disability. Features in these areas of technology include continuing evolution of new devices, further development of well-established approaches, a need for critical assessment, requirements for support from technical and health care workers, and the need to identify funding to achieve efficient programs. PMID- 7790167 TI - Adapting work sites for disabled persons using advanced technology. AB - This paper describes the technical approach in the TUFFA (Technology Procurement for Disabled in Working Life) project and a model for cooperating areas of competence based on a holistic view of the individual's abilities, the environmental conditions at the work site, and technical solutions. PMID- 7790169 TI - Outcome measurement in medical rehabilitation. AB - The Uniform Data System for Medical Rehabilitation (UDSmr) provides a method for uniform assessment of the severity of patient disability and the outcomes of medical rehabilitative care. The effectiveness and efficiency of medical rehabilitation services may be analyzed using the Functional Independence Measure (FIM), the functional assessment component of the UDS, and other data. Program evaluation models based on the UDSMR and the FIM are useful for measuring resource cost of disability. PMID- 7790168 TI - Assessment of rehabilitation technologies in stroke. Outcomes and costs. AB - Initial functional ability (Barthel Index, mean 57) was found to be an important predictor of functional ability 1 year after stroke (mean 80) and for costs during the period. On average the total cost for a stroke patient was about SEK 200,000; the main expense, accommodation, averaged about SEK 140,000, while assistive devices amounted to SEK 2,600. Those who use assistive devices, although having achieved a high functional ability, perceive and rate their life situation (Nottingham Health Profile) considerably more impaired than those without assistive devices. PMID- 7790170 TI - The cost of the Swedish handicap service system. Implications for technology assessment. AB - The total cost of the Swedish handicap system is estimated at US $10.7 billion for 1989. The cost is distributed across different authorities with separate legal and financial responsibility. The concept of technology must be extended to include consideration of both the resources spent and benefits gained in the public sector and the magnitude and distribution of transfer payments from social insurance to fulfill its function in handicap policy decision making. PMID- 7790171 TI - Cost-utility analysis of assistive technologies in the European Commission's TIDE Program. Technology Initiative for Disabled and Elderly People. AB - Socioeconomic evaluation is an issue dealt with in the European Commission's research program TIDE. The principles of cost-utility analysis have been examined for usability in the assessment of rehabilitative technologies. A case study, the choice of a type of wheelchair, is described to demonstrate how estimates of utility can be derived and how cost-utility ratios can be used to guide decision making. PMID- 7790173 TI - Deciding to buy expensive technology. The case of biliary lithotripsy. AB - Acquiring expensive, new medical technology requires an evaluation of the efficacy and effectiveness, safety, profitability, feasibility, and risk of a project in the context of the hospital's social responsibility and institutional strategy. A case study of the decision to bring biliary lithotripsy to Strong Memorial Hospital illustrates how these criteria offer managers a coherent approach to difficult and consequential decisions about acquiring medical technology. PMID- 7790172 TI - The development of health care technology assessment. An international perspective. AB - We consider the nature of technology assessment and then briefly summarize technology assessment activities in five countries: Canada, France, the Netherlands, the United Kingdom, and the United States. Drawing from these examples, we then identify determinants of the emergence and impact of technology assessment. PMID- 7790174 TI - Physicians' opinions and use of controversial technologies. The case of mammographic screening in Norway. AB - In a survey of 196 Norwegian radiologists and 37 breast imaging centers, physicians' preferences were found to be likely to influence the use of mammography. In their decision making, the radiologists appear to be influenced by income motives and by perceptions of the risk of misdiagnosing breast cancer. Despite opinions favorable to mammographic screening, most radiologists would prefer a CT scanner or a magnetic resonance imaging unit to a mammographic unit if the x-ray department were in a position to acquire capital equipment. PMID- 7790176 TI - Declining cost-effectiveness of screening for disease. The case of gastric cancer in Japan. AB - We examined the cost-effectiveness of screening for gastric cancer in hypothetical cohorts of asymptomatic Japanese ages 40, 50, 60, and 70, followed for 10 years. Current screening recommendations in Japan are not optimal. Although indirect x-ray is the correct method, screening for gastric cancer may not be cost-effective for Japanese under the age of 50. Policymakers worldwide should monitor the changing incidence of disease as they consider and recommend screening policies. PMID- 7790175 TI - Hemophilia home treatment. Economic analysis and implications for health policy. AB - This analysis describes the development of technology for home self-infusion of factor VII in the treatment of hemophilia and its clinical, economic, and social consequences, and uses the case study of such home care treatment to illustrate the potentials and pitfalls of formal economic analyses of programs to treat chronically ill children. A comprehensive review of all original data on hemophilia programs, their related costs, and outcomes, conducted from 1966 through 1993, examined the economic outcomes for two hypothetical cohorts, one aged 0-4 years and the other aged 30-34 years. Including the measurement of treatment effects on the productivity of parental caregivers substantially increases the benefit-cost relationship of an intervention directed at chronically ill children. Increased economic productivity and societal return resulting from such a program for young adults exceeds those for a cohort of children, primarily due to assumptions related to discounting. However, estimation of quality-adjusted life years favors the younger age cohort, since children survive for a longer period of time and with each year survived comes a higher quality of life. Unlike simpler instances in which economic benefits can be shown to outweigh resource costs, policy decisions concerning services for chronically ill children raise an additional set of complex analytic issues. Inclusion of the benefits in productivity experienced by family caregivers provides an important added dimension to such analyses. The development of cost benefit or cost-effectiveness analyses of these programs illustrates the importance of careful measurement of outcomes and explicit statements of underlying assumptions. Such an analysis of home care for children with hemophilia therefore demonstrates both the strengths and the limitations of this approach. PMID- 7790177 TI - Potential inconsistencies between cost-effectiveness and cost-utility analyses. An upstairs/downstairs socioeconomic distinction. AB - This paper indicates that certain economic evaluation methods (cost-effectiveness and cost-utility analyses) may yield inconsistent results. Along with the lack of formal grounding of these methods in economic "first principles," this finding suggests the possible benefit of greater reliance on the more formally developed method of cost-benefit analysis. PMID- 7790178 TI - "Continuing care': an emerging issue in European mental health policy. PMID- 7790179 TI - British approaches to the continuing care client. PMID- 7790180 TI - Psychiatric care and social support for people with long-term mental illness in Sweden. PMID- 7790181 TI - How can psychiatry survive without psychiatric hospitals? The Italian experience. PMID- 7790182 TI - Long-term mental illness in Germany. PMID- 7790183 TI - The dilemmas of chronicity: the transition of care policies from the authoritarian state to the welfare state in Spain. AB - In this article, the constitution of the population of chronic mental patients is examined for the period 1885 to 1975 as well as its influence on the design of reform programmes in the crisis of the Franco-ist state. Then follows an assessment of state reforms and regional policies with effect from 1980. Reference is made to the theoretical models utilised in this last period and to the tension and contradictions between professionals of bio-medical orientation and sectors sympathetic to community models sustained from the perspective of social psychiatry. PMID- 7790184 TI - Economic and legal aspects of mental health policies in Greece. PMID- 7790185 TI - Leros and the Greek mental health system. AB - In 1983 the Greek Ministry of Health, in presenting the new mental health law, described the state of the mental health system in the country as follows: "it is generally recognised that the psychiatric services in Greece are totally inadequate. The treatment inflicted on patients is often approaching the negation of the fundamental notions of human dignity. A radical reform is intended to change this intolerable situation." (EC, 1984). Eight years on, the state of the Greek mental health services can be defined as continuing to be 'serious' despite the attempts to change it and to apply the reform. PMID- 7790186 TI - The continuing care client. AB - In the present contribution, I would like to describe modes of care for people who, because of their mental health problems, need the continuing or occasional help of different institutions (Ramon, 1990). Some service structures are described which are the most outstanding. The history and organisation of relevant institutions, as well as possibilities for the improvement of their work, or alternatively their abolition, are also discussed. PMID- 7790187 TI - [Contact allergies to corticosteroids. Prevalence, cross-reactions and methods of detection]. AB - Topical corticosteroids (CS) are frequently used to treat of allergic contact dermatitis, so that their own potential for sensitization is rarely detected. However, increasing numbers of hypersensitivity reactions to corticosteroids have been reported during the last 10 years, and allergic skin reactions to over 50 particular compounds have been observed. CS must now be regarded as a rather frequent contact allergen, the prevalence being twice as high in women as in men. Contact allergy to CS is clinically characterized by a chronic and persistent, corticosteroid-resistant dermatitis. In general, hypersensitivity to CS is a type I and/or type IV mediated allergic reaction. Cross-sensitivity between individual corticosteroid preparations has been described owing to their closely related chemical structures (e.g. hydrocortisone and tixocortol pivalate). Contact allergy to CS can be confirmed by patch-tests, intradermal injection tests or application tests; because of the delayed appearance of positive skin reactions a prolonged evaluation period of up to 120 h is recommended. For routine screening the use of the patient's own material and of tixocortol pivalate and budesonide as test marker substances seems appropriate. The development of further marker substances is a target for ongoing research. PMID- 7790188 TI - [Recommendations for a photo-patch test standard series by the German speaking study group "Photopatch-Test"]. PMID- 7790189 TI - [Rare keratoacanthoma variants]. AB - Keratoacanthomas are made up of the same spinocellular differentiated cell material as squamous cell carcinomas, but they differ from the latter in origin and growth properties. The majority--in our series 98% of 741 examined cases--are of the "crateriform" type, which after rapid growth during the initial stage give way to spontaneous regression, mostly with complete restoration of the cutaneous structure. Less than 2% belong to the rare destructive variants with disturbed or absent regression and persistent invasive growth. Keratoacanthoma marginatum centrifugum, mutilating keratoacanthomas and aggregated keratoacanthomas can lead to extremely severe defects. None of the "conservative" treatment methods recommended in the literature up to now has proved effective, with the exception of surgery and radiotherapy with tumour ratio doses. Many publications are obviously based on uncritically interpreted individual observations. PMID- 7790191 TI - [Detection of nicotine in eccrine sweat after stimulation of sweat glands during nicotine withdrawal]. AB - The presence of nicotine in sweat obtained from smokers and one non-smoker exposed to tobacco smoke after 4 h to 8 days of nicotine-free time was investigated. Following stimulation of the eccrine glands, sweat samples were taken every hour for 6 h. The total nicotine concentrations, i.e. the sum of nicotine and its metabolites, were determined by radioimmunoassay. The presence of unchanged nicotine was revealed by gas chromatography/mass spectrometry. PMID- 7790190 TI - [Positive tuberculin reaction in sarcoidosis]. AB - Scar sarcoidosis is one of the rare cutaneous manifestations of sarcoidosis. Apart from the clinical picture, suppression of the cell-mediated immunity can often be determined when tuberculin tests and testing for recall antigens are carried out. In the present case of a 68-year-old woman patient scar sarcoidosis and pulmonary sarcoidosis were detected. Remarkably, a strongly positive tuberculin reaction was found, while acute tuberculosis and former BCG vaccination were excluded. Both references in the literature and the case presented demonstrate that a positive tuberculin test, while very unusual in sarcoidosis, does not however, preclude the diagnosis. On the basis of some case reports in the literature, our patient was treated with allopurinol; impressive improvement of both the skin and the pulmonary manifestations was noted. Despite the well-known phenomenon of spontaneous regression in sarcoidosis, we recommend a clinical trial with allopurinol as this substance is well tolerated. PMID- 7790193 TI - [Von Recklinghausen neurofibromatosis and dermal melanocytic nevi]. AB - Neurofibromas, cafe au lait macules and freckles in the axillary or inguinal regions are common manifestations of von Recklinghausen's neurofibromatosis (NF 1). Less known is the simultaneous appearance of dermal melanocytic naevi. We describe the case of a 21-year-old Vietnamese woman who showed generalized, multiple neurofibromas, a solitary plexiform neurofibroma in the left gluteal region and Lisch nodules. In addition, there were several large grey-blue macules histologically characterized by fusiform pigment-bearing cells in the dermis, which we diagnosed as persistent aberrant mongolian spots. In the right zygomatic region she presented a grey-blue, hair-bearing macule, which we saw as a variant of Ota's naevus. A genetic background for this coincidence of a systemic with a local phakomatosis can be supposed, as both Schwann's cells and melanocytes are derived from the neural crest. Such pathologic rearrangement in the embryogenesis of the cellular elements could be important for the pathogenesis of NF-1 and dermal melanocytic nevi. PMID- 7790192 TI - [Reticular elastolytic giant cell granuloma. A variant of the annular elastolytic giant cell granuloma]. AB - The case report presented describes a new variant of annular elastolytic giant cell granuloma. Over a period of 10 years, a 40-year-old woman had developed reticular, brown to livid, partly atrophic skin lesions on the shoulders and decolletee. The patient had no subjective symptoms. Histology revealed a patchy lymphohistiocytic infiltrate in the dermis, with many giant cells. Elastic fibres were less frequently found in these infiltrates; in a few of the giant cells and macrophages fragments of elastic fibres were demonstrated within the cytoplasm. There were no deposits of mucin. For this new variant we propose the term "reticular elastolytic giant cell granuloma." PMID- 7790194 TI - [Transformation of multiple basaliomas to squamous cell carcinomas in an HIV patient with Gorlin-Goltz syndrome]. AB - We report on a 32-year-old male patient with Gorlin-Goltz syndrome, who presented with excessive numbers of superinfected basal cell carcinoma. This led us to suspect an underlying HIV infection, which was confirmed by ELISA and Western blotting. Laboratory investigation of the immunological state revealed severe immunosuppression with 267 CD4+ lymphocytes and a CD4/CD8 ratio of 0.3. The histological picture showed multiple basal cell carcinomas, some of them transforming into squamous cell carcinomas. We suspect that the excessive number and the unusual clinical and histological picture of the basal cell carcinomas in this patient were probably influenced by the underlying HIV infection. PMID- 7790196 TI - [Green hair]. PMID- 7790195 TI - [Verruciform palmoplantar keratoderma as a characteristic marker of hidrotic ectodermal dysplasia of the Clouston type]. AB - We report on a 23-year-old man with hidrotic ectodermal dysplasia of the Clouston type showing a severe expression of his gene defect. As a prominent feature of this case, we describe the presence of verruciform keratoderma of hands and feet, and we visualize these skin changes by means of a new imprinting technique. PMID- 7790197 TI - [Significance of the serum ferritin level in porphyria cutanea tarda]. PMID- 7790198 TI - [120 years Dresden-Friedrichstadt Dermatology Clinic]. AB - The dermatology clinic in Dresden-Friedrichstadt this year celebrates 120 years of existence. It is one of the oldest dermatology clinics in Germany. The contribution presents an overview of the major events from the clinic's foundation as "External Section for Dermal and Venereal Diseases and Minor Surgery" in 1874 up to the present time. The clinic has played an important part in the development of the field of dermatology in Dresden. A brief account of the most important medical superintendents and of their scientific activities is given. PMID- 7790199 TI - [Idiopathic pustular and bullous variant of Sweet syndrome]. PMID- 7790200 TI - [Necrobiology of the skin: apoptosis]. PMID- 7790201 TI - A review of some available radioactive and non-radioactive substitutes for use in biomedical research. AB - The unavailability of disposal facilities for long-lived low-level radioactive waste (LLRW), expense associated with its disposal, and, for some generators, limitation of space to decay short half-life radioactive materials has prompted the search for alternatives to radiochemical techniques. Some of these alternatives are presented below. PMID- 7790202 TI - Radiocesium body burdens in immigrants to Israel from areas of the Ukraine, Belarus and Russia near Chernobyl. AB - Of the 500,000 immigrants from the former Soviet Union who came to Israel during 1990-1993, about 100,000 are estimated to have come from radiocontaminated areas near Chernobyl. These people were subject to chronic uptake of environmental radiocesium over protracted periods. During October-November 1991, a joint Israeli-Canadian investigation measured radiocesium body burdens in immigrants to Israel from the Ukraine, Belarus, and the southern Russian republic in order to provide factual information on radiocesium levels to concerned immigrants and to relate the body burdens to the geographic area of residence before coming to Israel. Assessments were made of 137Cs body burdens in 1,228 volunteer men, women, and children. These measurements were accompanied by medical assessments based on clinical histories and examinations. Radiocesium levels were strongly dependent on the duration of residence in Israel, with the highest levels being found in the most recent immigrants. The maximum level, extrapolated back to the time of leaving the former Soviet Union, was estimated to be about 0.83 kBq (10.3 Bq kg-1). Of the most recent immigrants from the Kiev region (< 101 days in Israel), only 15% had back extrapolated body burdens > 50 Bq, whereas 53% of those coming from Gomel and other towns in the contaminated zones (> 3.7 x 10(10) Bq km-2 of radiocesium) had detectable levels > 50 Bq. People coming from the latter region had significantly higher body burdens as compared to those from the former, in accordance with the higher degree of ground radiocesium contamination reported for the latter region. Women and children showed considerably lower total radiocesium content in comparison to men. All radiocesium body burdens at the time of measurement were too low to be of health concern. PMID- 7790203 TI - The regression effect as a cause of the nonlinear relationship between short- and long-term radon concentration measurements. AB - The relationship between four-day charcoal canister radon measurements and year long alpha-track detector measurements in 983 New Jersey homes has been recently examined by others. The ratio of canister measurement to long-term measurement for the homes in the survey, a common parameter of interest, was found to increase as the canister measurement increased. The examination presented considerable discussion of the variation of the ratios as functions of various parameters. Although we did not examine the raw data used in the study, it appears that many of the results (and perhaps those in other papers) are consistent with a simple model in which both the long-term and rescaled short term measurements provide measurements with error of the annual-average radon concentration in the home with no nonlinearity or other unusual functional dependence on radon concentration. We provide an example and discussion of this result, which is due to the widely known but frequently misunderstood phenomenon called "regression toward the mean," or simply the "regression effect." This does not invalidate the work of others; we merely wish to bring attention to the fact that the results in these papers may have a very simple explanation. PMID- 7790204 TI - Freeze-drying as a potential mean for waste handling of animal carcasses containing radioactive material. PMID- 7790205 TI - Pretreatment of animal wastes containing radioisotopes with dry-distillation. AB - Mice that had been radiolabeled with one of seven isotopes by intraperitoneal or subcutaneous administration were dry-distilled at 800 degrees C for 10 min, and the fate of the radionuclide was examined. The radionuclides administered were 3H, 14C, 32P, 35S, 45Ca, 51Cr, and 125I, all of which are commonly used in animal experiments. After dry-distillation, 95% of 3H was found in the distillate (condensate), and 80% and 16% of 14C were recovered from exhaust gas and residual solids, respectively. Only between 10 and 20% of 35S was found in distillate. The remainder of the residual 35S was recovered from the inner wall of the exhaust vent of the dry-distillation equipment. About 24% of 125I was also recovered from the inner wall of this same exhaust vent, and the residual radioactive materials were recovered from the residual solids. On the other hand, 32P, 45Ca, and 51Cr were recovered entirely from the residual solids. The weight of the animals decreased to about 10%, and the volume to about 20% (mice and rats) to 40% (rabbits) after dry-distillation. The residual solids of animal wastes generated by dry-distillation were odorless and chemically and biologically stable. Dry distillation has many merits as a pretreatment for the disposal of animal wastes containing radioactive material because of the easy handling, storage, and transportation of the residual solids. PMID- 7790206 TI - An industry survey of current lower limits of detection for various radionuclides. AB - The results of a survey to assess detection limits of various radionuclides and their associated costs is presented herein. Included among the radionuclides of interest are mixed fission products, mixed activation products, actinides and transuranics, plus tritium (3H) and 14C. The survey encompassed commercial analytical radiochemistry services and nuclear instrument suppliers in the United States. In the study, a simple soil sample was defined as the object of consideration with no requirements for any special quality control/assurance. Standard procedures and instrumentation were requested, as were standard prices/costs required for the various analyses. The minimum detectable level for most isotopes using standard procedures was on the order of 0.0037 to 0.037 Bq g 1 (0.1 to 1.0 pCi g-1). The analytical costs varied by factors of 2 to 4 over a range of 0.0037 to 0.37 Bq g-1 (0.1 to 10.0 pCi g-1). While the ability to detect below 0.0037 Bq g-1 (0.1 pCi g-1) is possible, the required detection times were considered prohibitive for a commercial laboratory. PMID- 7790208 TI - Clarification of whole body dose. PMID- 7790207 TI - Shielding and radiation safety around a superconducting cyclotron neutron therapy facility. AB - Prior to routine operation of the neutron therapy unit a radiation survey was performed in order to confirm the shielding design and to assure the safety of the personnel involved in the operation of the unit. The shielding requirements were calculated in accordance with NCRP Report No. 51. The contributions of the neutron and gamma dose equivalents have been measured separately outside the treatment room. The exposure outside the shield is negligible. In general, the measured values were lower than those derived from the shielding calculations. The highest total dose equivalents were registered at locations corresponding to the highest calculated values. PMID- 7790209 TI - Spatial and temporal responses of ionization chambers. PMID- 7790210 TI - Radiation dose to the population of Slovak Republic from diagnostic nuclear medicine. AB - This study estimated the radiation exposure attributed to nuclear medicine examinations during the period of 1985 through 1992 in Slovak Republic. It was accomplished by survey of nuclear medicine facilities from 1987 to 1992. In addition, a detailed analysis of nuclear medicine practice was obtained for 1992. The mean effective dose equivalent per capita and per exam were 0.022 mSv and 3.8 mSv, respectively. The collective effective dose equivalent for 1992 was 110.7 person Sv. In conclusion, the practice of nuclear medicine produces a very low radiation dose per examination and per capita of population. The Slovak Republic appeared favorable in comparison to other countries in the judicious use of diagnostic nuclear medicine procedures. PMID- 7790211 TI - Rapid monitoring of soil, water, and air dusts by direct large-area alpha spectrometry. AB - During retrieval and disposition of wastes containing transuranium elements, continuous monitoring of the air, water, and soil for alpha emitters was required to ensure that safety limits were not exceeded and that the waste itself was not disturbed unknowingly. Direct measurements by alpha spectrometry were particularly promising because of their potential speed, sensitivity, and their ability to identify transuranium radionuclides under field conditions. Soil samples or settled dusts were finely ground, suspended in 80% ethanol, sprayed onto circular stainless steel pans, and dried on a hotplate. Water samples were mounted directly by spraying. Air dusts were collected with a high-volume air sampler on 20- by 25-cm membrane filters. The samples were then analyzed directly in a large pressurized gridded ionization chamber without further sample preparation. The lower limits of detection for 10-min counting times were 1.5 Bq g-1 (40 pCi g-1) for 100-mg soil samples, and 4 x 10(-2) Bq m-3 (10(-12) microCi mL-1) for a 10-min air sample taken at 0.4 m3 min-1 (14 cubic feet per minute) and counted without waiting for decay of radon progeny. PMID- 7790212 TI - Variations in astronaut radiation exposure due to anisotropic shield distribution. AB - The dose incurred in an environment generated by extraterrestrial space radiations within an anisotropic shield distribution depends on the orientation of the astronaut's body relative to the shield geometry. The fluctuations in exposure of specific organ sites due to astronaut re-orientation are found to be a factor of 2 or more in a typical space habitation module and typical space radiations. An approximation function is found that overestimates astronaut exposure in most cases studied and is recommended as a shield design guide for future deep space missions. PMID- 7790213 TI - Type testing of the Siemens Plessey electronic personal dosemeter. AB - This paper presents the results of a laboratory assessment of the performance of a new type of personal dosimeter, the Electronic Personal Dosemeter made by Siemens Plessey Controls Limited. Twenty pre-production dosimeters and a reader were purchased by Ontario Hydro for the assessment. Tests were performed on radiological performance, including reproducibility, accuracy, linearity, detection threshold, energy response, angular response, neutron response, and response time. There were also tests on the effects of a variety of environmental factors, such as temperature, humidity, pulsed magnetic and electric fields, low- and high-frequency electromagnetic fields, light exposure, drop impact, vibration, and splashing. Other characteristics that were tested were alarm volume, clip force, and battery life. The test results were compared with the relevant requirements of three standards: an Ontario Hydro standard for personal alarming dosimeters, an International Electrotechnical Commission draft standard for direct reading personal dose monitors, and an International Electrotechnical Commission standard for thermoluminescence dosimetry systems for personal monitoring. In general, the performance of the Electronic Personal Dosemeter was found to be quite acceptable: it met most of the relevant requirements of the three standards. However, the following deficiencies were found: slow response time; sensitivity to high-frequency electromagnetic fields; poor resistance to dropping; and an alarm that was not loud enough. In addition, the response of the electronic personal dosimeter to low-energy beta rays may be too low for some applications. Problems were experienced with the reliability of operation of the pre-production dosimeters used in these tests. PMID- 7790215 TI - Radon entry control in new house construction. AB - People exposed to high concentration levels of radon face an increased risk of developing lung cancer. The risk is directly proportional to the length and level of radon exposure. Because of health reasons, it is safer to build new houses with radon mitigation systems installed in slab-on-grade houses. However, the interrelationships between parameters and factors governing radon entry and control are highly complex. A study performed by the University of Florida has examined the effectiveness of different radon entry control approaches. The analysis was based on 47 houses from three research projects conducted by the University of Florida (14 houses), Florida Solar Energy Center (13 houses), and GEOMET Technologies (20 houses). The evaluation of the performance and effectiveness of improved floor slabs, space conditioning, and ventilating systems were analyzed. Statistical analyses of the interrelationship between various parameters were also performed. Study findings such as the important factors in reducing radon entry and the effectiveness of passive construction approach and active subslab depressurization systems are presented in this paper. PMID- 7790214 TI - Evaluation of the 131I thyroid-monitoring measurements performed in Ukraine during May and June of 1986. AB - After the Chernobyl accident in 1986, about 150,000 monitoring measurements were performed in Ukraine. From this data base, 40,000 measurements were selected for which the results of the reference-source measurements could be analyzed by statistical means. The majority of these measurements are of high quality. In this paper, the uncertainties introduced due to the variabilities of anatomic parameters and the measurement geometry are quantified by measurements using a thyroid-neck phantom. Parameters considered are the thyroid mass, the thickness of the tissue overlying the thyroid as well as the detector-neck distance, the orientation, and the horizontal and vertical position of the detector. The uncertainty introduced due to the variability of these factors corresponds to a coefficient of variation in the range of 25-40% for the measured activity. PMID- 7790216 TI - 222Rn progeny surface deposition and resuspension--residential materials. AB - The radiological hazard of radon gas to occupants in residential environments is from the particulate progeny 218Po, 214Pb, 214Bi, and 214Po, rather than 222Rn itself. Attachment to aerosols, plateout, and resuspension impact on the progeny airborne concentrations. Plateout rate and resuspension factors were measured for air change (ventilation) rates, 0.01 to 1.0 h-1, in a 0.28 m3 test chamber for interior residential materials of wallboard, drapery, carpet, ceiling tile, and concrete, and from 0.05 to 2.5 h-i for hardwood and glass. The overall accuracy of the plateout rate values is estimated to be +/- 13% standard deviation. For the different materials, the plateout rates for 218Po progeny varied by a factor of nearly six. Drapery gave the largest plateout rates. Resuspension rate factors, R, were measured for hardwood, wallboard, drapery, carpet, and glass by a new time-dependent measurement method based on the difference in buildup rate of 214Po to equilibrium caused by resuspension. Values for R obtained for hardwood, wallboard, drapery, carpet and glass were 0.31, 0.29, 0.44, 0.55, and 0.36, respectively ( +/- 30% standard deviation). All measurements were made in a continuous air conditioned interior environment maintaining temperature at 22.2 +/- 1.1 degrees C and relative humidity of 30% +/- 10%. Computations were made of equivalent plateout rates and equilibrium fractions for a standard 5 m x 5 m x 3 m high room to provide values to compare with other work. PMID- 7790217 TI - Estimates of radiogenic cancer risks. AB - A methodology recently developed by the U.S. EPA for estimating the carcinogenic risks from ionizing radiation is described. For most cancer sites, the risk model is one in which age-specific, relative risk coefficients are obtained by taking a geometric mean of the coefficients derived from the atomic bomb survivor data using two different methods for transporting risks from the Japanese to the U.S. population. The risk models are applied to estimate organ-specific risks per unit dose for a stationary population with mortality rates governed by 1980 U.S. vital statistics. With the exception of breast cancer, low-LET radiogenic cancer risk estimates are reduced by a factor of 2 at low doses and dose rates compared to acute high dose exposure conditions. For low dose (or dose rate) conditions, the risk of inducing a premature cancer death from uniform, whole body, low-LET irradiation is calculated to be 5.1 x 10(-2) Gy-1. Neglecting nonfatal skin cancers, the corresponding incidence risk is 7.6 x 10(-2) Gy-1. High-LET (alpha particle) risks are presumed to increase linearly with dose and to be independent of dose rate. High-LET risks are estimated to be 20 times the low-LET risks estimated under low dose rate conditions, except for leukemia and breast cancer where RBEs of 1 and 10 are adopted, respectively. PMID- 7790219 TI - Establishing a surveillance system for infections acquired in home healthcare. AB - Marin Home Care has developed a simple surveillance system that quickly produces monthly statistics of incidence rates of infections acquired while the patient is on service. Supplemental orders and culture results are reviewed, and combined with computer reports each month. The tables generated give the rates of infection for symptomatic urinary tract infections in patients with indwelling Foley catheters, and bloodstream infections in patients receiving intravenous therapy. PMID- 7790218 TI - Nursing research in HIV/AIDS home care, Part 1: Importance and methods. AB - One of the primary goals of nursing research is to develop a systematic body of knowledge to guide nursing practice. In the community setting, an extremely useful method of research is the exploratory field study, which can be used to discover important variables that may exist in real-life situations. This study reflects an analysis of the problems that were identified in persons living with human immunodeficiency virus/acquired immune deficiency syndrome in New York City who were referred for home care services. Part I presents an overview of nursing research methods, focusing on an actual field study in human immunodeficiency virus/acquired immune deficiency syndrome home care; Part II describes the results and implications for nursing. PMID- 7790221 TI - Taking the leap of faith: applying continuous quality improvement techniques to home care. AB - Methods of evaluating quality in home care are undergoing fundamental change. Accrediting bodies, such as JCAHO and NLN's CHAP have implemented new home care standards that address quality improvement rather than the familiar quality assurance. This article introduces the concept of continuous quality improvement and demonstrates its application in a home care setting. PMID- 7790220 TI - Lyme disease: an emerging infection with home healthcare implications. AB - The 11,424 cases of Lyme disease reported in 1994 represented a nearly 40% increase from the previous year. The dramatic increase of Lyme disease in the United States points to the need for home healthcare nurses to review their knowledge of the clinical manifestations, treatment, and prevention measures for this emerging infection. PMID- 7790222 TI - Geriatric depression. AB - In late life, depression is the most prevalent functional psychiatric disorder. Because the presentation may be multicausal and clinically complex, early assessment of biologic and psychosocial factors, diagnosis, and appropriate referral are important in ameliorating the associated morbidity and mortality. Nurses must have current knowledge and skills to assess mood states of elderly persons and to implement appropriate interventions. Successful management of depression in the elderly results in a reformulation of purpose and an enhanced quality of life. PMID- 7790223 TI - Assessment of depressed older persons living in a home setting. AB - This article discusses the complexity of assessing depression in older persons in a home setting. The author describes using the Older Adults Resource Survey to determine functional status in five domains. Other components essential to assessment of depression include inventory of medications, the Short Portable Mental Status questionnaire, the Mini-Mental Status, the Geriatric Depression Scale, a suicide assessment, and a drinking history. PMID- 7790224 TI - "Power pudding": natural laxative therapy for the elderly who are homebound. AB - "Power Pudding" is a natural laxative recipe for relieving and preventing constipation. Its ingredients are nutritious and inexpensive. A small study conducted at a home care agency in northern Virginia demonstrated the effectiveness of "Power Pudding" with several elderly clients who were homebound. As a nursing intervention, it has good potential for improving bowel function in the elderly home care population. PMID- 7790226 TI - Clinical indicators for the psychiatric home health nurse. PMID- 7790225 TI - Wound care and the human immunodeficiency virus. PMID- 7790227 TI - December 1994 updates to home health and hospice regulations. PMID- 7790228 TI - Principles of productivity. PMID- 7790229 TI - Looking for the good. PMID- 7790230 TI - Home care: a touching experience. PMID- 7790231 TI - [Osteosynthesis plates in the area of the facial skull--yes or no?]. PMID- 7790233 TI - [Voice rehabilitation after laryngectomy with tracheoesophageal prosthesis. Analysis with special reference to psychosocial factors]. AB - The first 2 years' experiences with Provox prostheses at the ENT Clinic of the University of Berne are discussed. Thirty-three prostheses were inserted after primary tracheoesophageal puncture and 5 after secondary puncture. Voice success was measured with the scale of Robillard Shultz and Harrison, which encompasses not only assessment of voice quality but also frequency of use and a patient's independence in prosthesis care. After primary puncture the percentage of "functional" speakers increased progressively from 26% after 2 months to 56% after 1 year. After secondary puncture only 2 of 5 patients became functional speakers after 6 months. Because only a few of the previously laryngectomized patients who were informed about the possibility of a secondary puncture wished to receive a prosthesis, the reasons for their reservation were analyzed. Uneasiness about an additional operation and fear of complications were the most frequent motives. Further psychosocial aspects--including the unwillingness of some patients to use their fully functioning prosthesis--are discussed. PMID- 7790232 TI - [Should osteosynthesis plates in the area of the facial skull be removed again? Results of experimental and clinical studies]. AB - We discuss the arguments dealing with removal of fixation devices and plates after osteosynthesis of facial bone fractures. As an experimental model for examining the soft tissue reaction to implants under standard conditions, an inguinal flap was prepared in 24 Wistar rats. Titanium mesh implants (10 x 8 x 0.3 mm) were then inserted into the flaps. Twelve implants were additionally bent to investigate histologically the influence of mechanical preparation on tissue reactions. Examination of all specimens was carried out with the technique of Donath and showed a thin capsule around the titanium implants but without any signs of infection. Around the bent areas of the implants there were minimal signs of local chronic inflammation without a capsule. Use of titanium microplates instead of miniplates in 89 patients with midfacial fractures diminished the rate of local complications. Based on our experimental and clinical results, indications for the different types of plates and the necessity for their later removal are discussed. Our present plates are only removed from the maxillary sinus wall and the alveolar ridge, after osteosynthesis in children, and in patients with local complications. If removal of the material is planned (because of the location), less expensive steel implants are used. PMID- 7790234 TI - [Modifying the stapes footplate with various laser systems. II. The pulsed laser]. AB - The object of the present study was to examine the tissue ablation capacity of various pulsed lasers at the stapes footplate. Isolated human stapes and bovine compact-bone platelets (thickness 90 microns) were used to determine effective laser parameters for achieving a perforation measuring 500 microns to 600 microns in diameter. Apart from achieving the perforation diameters, particular attention was given to the form and quality of the perforations, reproducibility of the perforation effect and the thermally altered border zones occurring at the footplate. Four pulsed laser systems were used: excimer, Ho:YAG, Er:YSGG and CO2 lasers. An adequately large perforation generally could only be achieved by several repeated shots at the same application site, since only a small amount of tissue was ablated per application. The mechanism of the photoablation caused the extent of the thermal side effects to be markedly lower than with the continuous wave (cw) and superpulse systems. For this reason and because of their highly reproducible perforation effect, they were basically better suited for stapedotomy than the cw systems. It was possible, however, that as a result of the longer application time and the need to repeatedly irradiate the same application site, the higher pulse counts could prove to be disadvantageous in clinical practice. Among the pulsed laser systems, the Er:YSGG laser had the highest ablation rate at the stapes and was thus the most effective laser for interventions at the footplate. Although somewhat less effective than the Er:YSGG laser in our studies, the Ho:YAG and pulsed CO2 lasers also appear to be suitable for stapes surgery. On the other hand, we did not consider the excimer laser (308 nm) to be particularly effective at the footplate because of its low ablation rates. PMID- 7790235 TI - [The value of fine needle aspiration cytology in suspected neoplastic salivary gland enlargement]. AB - Imaging offers little support in the management of salivary gland masses suggestive of a neoplastic lesion. There are also contraindications for a surgical biopsy in many cases. Fine-needle aspiration cytology (FNAC) is not yet widely recognized as a diagnostic tool. To date, 206 FNAC were carried out from 1986 through 1993 on 181 consecutive patients and were reviewed in the present study. Histological confirmation was possible in 174 tests, while 32 were confirmed on clinical follow-up. In sum, 192 samples were sufficient for interpretation, 10 were questionable by our standards and 4 were non-diagnostic. One hundred-seventy-one samples were true-negative, 27 true-positive, 4 false negative and 4 false-positive. Sensitivity was 87.1% and specificity 97.7%. Out of 141 primary diagnostic procedures in which a final histologic diagnosis was available, FNAC was able to determine histogenesis in 113/124 benign lesions and 9/17 malignant masses. These included 65/67 pleomorphic adenomas and 21/22 adenolymphomas. In 8 cases a diagnosis of "adenoma" was made. Difficulties in interpretation were found in lesions that were mucoepidermoid carcinomas and, in part, adenoid cystic carcinomas. No complications occurred. Provided that there was sufficient experience in performing the aspiration technique and in cytologic interpretation, FNAC was found to be a quick, reliable, low-cost, easy-to-perform method with low risk in the management of nearly all benign and most malignant salivary gland lesions. PMID- 7790237 TI - [Rare tumor of the nose and paranasal sinuses. Leiomyosarcoma]. AB - Leiomyosarcoma is a rare malignant tumor of the nose and paranasal sinuses. Including our patient, 32 cases have been reported in the literature. Radical surgery is currently the best therapy. In comparison with results of conventional irradiation, postoperative neutron treatment appears to be more effective. PMID- 7790238 TI - [Kikuchi lymphadenitis. A contribution to the differential diagnosis of cervical lymph node swelling of unknown origin]. AB - According to its morphological appearance, Kikuchi's disease is also called "histiocytic necrotizing lymphadenitis". This disorder was first described in Japan in 1972 as a benign lymphadenopathy of the neck. In Germany only a few cases have been reported by pathologists, whereas most clinicians are unaware of the existence of this rare disease, which can easily be mistaken for malignant lymphoma. In 1993 three cases of Kikuchi's lymphadenitis were treated at the ENT Department of the University of Lubeck. Patients' ages ranged from 15 to 30 years old. Except for cervical adenopathy, findings in blood tests, viral serology and radiological imaging were unremarkable. While fine needle aspirations were suspicious for malignant lymphoma, a final diagnosis of self-limiting "Kikuchi's lymphadenitis" was established histologically from excised lymph nodes. In our opinion early extirpation of lymph nodes and consultation of a pathologist are necessary to make a correct diagnosis without delay. Thus, in patients with Kikuchi's lymphadenitis unnecessary staging procedures and treatment can be avoided. PMID- 7790236 TI - [Empirical studies of music listening habits of adolescents. Optimizing sound threshold limits for cassette players and discoteques]. AB - The music habits of 569 pre-teens and teenagers, between 10 and 17 years of age, were examined and exposure to music from portable music players was compared to that in discotheques. Using a questionnaire we determined the length of time spent listening to portable music players and the frequency of disco visits. The individual level of the music heard through portable music players was measured as a free-field corrected short term mean level. The total music exposure (related to 40 hours per week) was calculated from the data and different assumed disco sound levels. We estimated the risk of ear damage according to ISO 1999 standards on the basis of the total music exposure, whereby the mean disco level was varied as a parameter in the range of 95 to 110 dB(A). Taking only the portable music players into account, one can expect that even after 5 years of music, approximately 5% of the total group would have a hearing loss of 20 dB. This percentage clearly rises when additional exposure is given in discotheques having music levels above 100 dB(A). We suggest therefore that for safety reasons the following sound levels should be observed: 90 dB(A) for portable music players and 95 dB(A) for discos. Through adherence to these levels we would expect that 1% of the young people in our study would have a hearing loss > 10 dB, whereas momentary exposure would result in a hearing loss > 10 dB of 10-20%. Therefore we believe that sound level limitations should be enacted immediately for portable music players and in discotheques. PMID- 7790239 TI - [Does summer smog damage the nasal mucosa and contribute to bacterial rhinitis?]. AB - Smog in hot summers contains noxious agents resulting from the combustion of fossil fuels whose levels are highest in industrial areas. Reactions of the oxygen radical of ozone with sulfur dioxides, nitrous oxides, hydrocarbons and the water molecules of the nasal mucous membrane presumably support the formation of acids such as H2SO4 or HNO3 (from H2SO3 or HNO2 [3, 4]). Acid corrosion seems to damage the mucous membrane, leading to local erosions, bleeding, and necrotic changes. The collapsed local defense system and necrotic mucosa are an ideal culture medium for a wide spectrum of pathogenic bacteria. Main signs of tissue pathology are bleeding spots or pustules, nasal congestion, degenerative mucositis, pruritus, as well as epipharyngeal and pharyngeal irritation. Therapy is possible with topical or oral antibiotics. Prophylaxis includes avoiding touching the mucous membranes and reducing outdoor activity on hot summer days. Further clinical and scientific examination would be helpful in determining additional explanations. PMID- 7790240 TI - [Voice rehabilitation after laryngectomy with the Provox voice prosthesis. Surgical and technical aspects. II]. PMID- 7790241 TI - Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. AB - PURPOSE: The objectives of this study were to determine the efficacy and toxicity of Etanidazole (ETA), a hypoxic cell sensitizer, when combined with conventional radiotherapy (RT) in the management of advanced head and neck carcinomas. METHODS AND MATERIALS: From March 1988 to September 1991, 521 patients who had Stage III or IV head and neck carcinomas were randomized to receive conventional RT alone (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 fractions per week) or RT+ETA (2.0 g/m2 thrice weekly for 17 doses), of whom 504 were eligible and analyzable. Treatment assignments were stratified before randomization according to the primary site (oral cavity + hypopharynx vs. supraglottic larynx + oropharynx + nasopharynx), T-stage (T1-3 vs. T4), and N-stage (N0-2 vs. N3). Pretreatment characteristics were balanced. In the RT-alone arm, 39% of patients had T3 and 34% had T4 disease, whereas in the RT+ETA arm, 42% of patients had T3 and 33% had T4 disease. Thirty-eight percent of the RT-alone patients and 37% of the RT+ETA patients had N3 disease. The median follow-up of surviving patients was 3.38 years, with a range between 0.96 and 5.63 years. RESULTS: One hundred and ninety four of the 252 (77%) RT+ETA patients received at least 14 doses of the drug. Overall RT protocol compliance rate was 82% in the RT-alone arm and 86% in the RT+ETA arm. No Grade 3 or 4 central nervous system or peripheral neuropathy was observed in the RT+ETA arm. Eighteen percent of the patients developed Grade 1 and 5% developed Grade 2 peripheral neuropathy. Other drug related toxicities included nausea/vomiting (27%), low blood counts (15%), and allergy (9%). Most of these toxicities were Grade 1 and 2. The incidence of severe acute and late radiation effects were similar between the two arms. The 2-year actuarial local regional control rate (LCR) was 40% for the RT-alone arm and 40% for the RT+ETA arm. Two-year actuarial survival was 41% for the RT-alone arm and 43% for the RT+ETA arm (p = 0.65). Multivariate analyses were performed to investigate the influence of covariates on treatment effects. A strong treatment interaction with N-stage was revealed: LCR (50% vs. 40% at 2 years), RT+ETA improved for patients with N0-2 disease but not for N3 patients (22% for RT+ETA and 40% for RT). Further analyses showed that RT+ETA was more advantageous in N0-1 patients, with a 2-year LCR of 55% for RT+ETA vs. 37% for RT only (p = 0.03). A similar phenomenon was observed when using survival as the end point. CONCLUSION: The results showed that adding Etanidazole to conventional RT produced no global benefit for patients who had advanced head and neck carcinomas. There was a suggested benefit for patients who had N0-1 disease, and that needs to be confirmed by another study. PMID- 7790242 TI - Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13. AB - PURPOSE: The objective of this study was to examine the incidence of late effects of hyperfractionated radiotherapy for head and neck cancer as a function of the dose delivered, as well as the daily interfraction interval. In addition, we wished to examine the influence of other prognostic factors including age, gender, primary site, T- and N-stage, and overall stage on the late effects of hyperfractionated radiotherapy. METHODS AND MATERIALS: Between 1983 and 1987, 479 patients with advanced head and neck cancer were entered on a Phase ILE/II dose escalation trial of hyperfractionated radiotherapy. They were randomly assigned to receive a dose of 67.2, 72.0, 76.8, or 81.6 Gy, delivered at 1.2 Gy/fraction, twice a day (BID), 5 days/week. Of the 451 analyzable patients, 399 patients who received > or = 64.8 Gy and had a follow-up > 90 days were eligible for this study. Acute and late effects were scored with the RTOG/EORTC late radiation morbidity scoring scheme. For this analysis, patients were subclassified by the actual doses delivered and by an average daily interfraction interval of < or = 4.5 h or > 4.5 h. The incidence of late effects was estimated using a cumulative incidence approach. RESULTS: Fifty-nine patients received 67.2 +/- 2.4 Gy, 119 received 72.0 +/- 2.4 Gy, 98 received 76.8 +/- 2.4 Gy, and 123 received 81.6 +/- 2.4 Gy. The proportion of patients treated with a daily interfraction interval of > 4.5 h was 32, 50, 43, and 71%, respectively. The four treatment groups were well balanced with respect to pretreatment characteristics. The median follow-up was 1.71 years (range: 0.24-9.6) for all evaluable patients and 6.12 years for 85 alive patients. There was no significant difference in the incidence of late effects between the different dose levels. At 5 years, the cumulative incidence of late effects was 17, 14, 20, and 13% for grade 3, and 7, 3, 7, and 5% for grade 4. However, the incidence of late effects differed significantly with respect to daily interfraction interval. The cumulative incidence of grade 4 late effects increased from 6.3% at 2 years to 7.5% at 3 years to 8.0% at 4 years and 8.6% at 5 years with an interval of < or = 4.5 h, while it remained at a constant of 2.0% with an interval of > 4.5 h during the same period (p = 0.0036). Multivariate analysis showed that among the prognostic factors examined, daily interfraction interval of < or = 4.5 h was the only significant independent prognostic factor for the development of grade 3+ or grade 4 late effects (p = 0.0167 and p = 0.0013, respectively). CONCLUSION: Results of this randomized Phase ILE/II trial of hyperfractionated radiotherapy in head and neck cancer showed no apparent dose-response relationship for late effects within the range of 67.2-81.6 Gy. Daily interfraction interval was a significant independent factor for the development of late effects in a multivariate analysis. PMID- 7790243 TI - Randomized phase I/II trial of two variants of accelerated fractionated radiotherapy regimens for advanced head and neck cancer: results of RTOG 88-09. AB - PURPOSE: To establish the feasibility of performing split-course accelerated hyperfractionation (AHFX-S) and concomitant boost accelerated fractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the tumor clearance rate and acute and late toxicity of these fractionation schedules. METHODS AND MATERIALS: Between February 1989 and January 1990, 75 patients with Stage III or IV squamous cell carcinoma of the head and neck were randomized to receive: (a) AHFX-S: 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy; or (b) AFX-C: 1.8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 weeks to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment during the last 11 treatment days, to a total dose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were scored according to the RTOG normal tissue reaction scales and tumor clearance was evaluated at completion of therapy and at regular intervals thereafter. RESULTS: Of the 70 analyzable patients, 38 received AHFX-S and 32 received AFX-C. The two arms were balanced with respect to sex, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX-C arm. The median follow-up was 2 years (range: 0.03-4.87 years). Tolerance of both variants of accelerated fractionated radiotherapy was satisfactory. There was no significant difference in local regional control, disease-free survival, or survival between the two arms. The 2 year local-regional failure rate, survival, and disease-free survival was 50, 50, and 40%, respectively, for the entire group of patients. Acute radiation mucositis was increased in both arms. There was no significant difference in the incidence of grade 3 acute toxicities (63% vs. 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxicities. Permanent grade 4 late toxicity was observed in 6 and 7% of the patients, respectively. CONCLUSION: Results of this randomized Phase I/II trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, local regional control, disease-free survival, or survival in this small scale study. Therefore, a Phase III trial comparing the relative efficacy of these two accelerated fractionation schedules against standard fractionation and hyperfractionation has been activated. PMID- 7790244 TI - Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial. AB - PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity. PMID- 7790245 TI - Salvage surgery following radiation failure in squamous cell carcinoma of the supraglottic larynx. AB - PURPOSE: We analyzed the clinical course of patients who developed local (primary) recurrence following high-dose irradiation of squamous cell carcinoma of the supraglottic larynx. METHODS AND MATERIALS: Between October 1964 and July 1991, 206 patients with previously untreated squamous cell carcinoma of the supraglottic larynx underwent radiotherapy with curative intent. Local failure occurred in 46 (22%) patients. Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. RESULTS: Sixteen patients did not undergo salvage surgery because of refusal (7 patients), severe medical illness (2 patients), concurrent distant metastasis (5 patients), or unresectable neck disease (2 patients). Twenty-six patients underwent total laryngectomy, and 4 patients had a voice-sparing procedure. Successful salvage was achieved in 50% of patients who underwent surgery. The rate of successful salvage did not correlate with preirradiation T-stage or time to failure after irradiation. Most of the failures after surgery were because of failure to control the primary cancer. The overall rate of postsurgical complications was 37%. No operative or perioperative deaths occurred. The 5-year survival rate for all 46 patients, calculated from the date of irradiation failure, was 20%, while the 5-year survival rate after salvage surgery for the 30 patients who underwent the procedure was 29%. CONCLUSION: There are few data in the literature regarding the clinical outcome in patients whose tumors are not controlled by initial radiotherapy. In the current and previous series, one-half to two-thirds of patients who developed primary failure underwent salvage surgery, which was successful in approximately half of the operated patients, leading to a 25-30% rate of long-term disease-free survival among the entire group of patients who developed failure. PMID- 7790246 TI - Outcome following radiotherapy in verrucous carcinoma of the larynx. AB - PURPOSE: To evaluate the outcome of patients with verrucous carcinoma of the larynx treated at the Princess Margaret Hospital with respect to control rates with radiotherapy, the salvage of local failure, the risk of regional lymph node metastasis following radiation therapy, and the risk of anaplastic transformation following radiotherapy. METHODS AND MATERIALS: Forty-eight patients underwent primary treatment for verrucous carcinoma of the larynx in the period between January 1961 and December 1990. This represented 1.1% of cases of laryngeal cancer seen in this time period. Forty-three received radiotherapy and 5 had surgery as the primary treatment. Several radiation dose-fractionation schedules were used, the most frequent being 50 Gy in 20 fractions in 4 weeks (31 cases), while eight patients were treated with 55 Gy over 5 weeks. RESULTS: The 5-year rate of local control was 59% for the 43 patients treated with radiotherapy. Surgical salvage was universally successful in all cases where it was attempted. The five cases treated with surgery alone did not experience relapse. Only one patient died of verrucous carcinoma. He had been medically unfit for surgical intervention at the time of initial treatment and at the time of relapse. He underwent a truncated course of radiotherapy (24 Gy in 3 fractions over three weeks in 1975). There was no evidence of increased neck relapse compared to other forms of laryngeal carcinoma following radiation treatment. No evidence to support anaplastic transformation of tumors treated with radiotherapy was evident in this series. CONCLUSIONS: Local control using radiation treatment is less successful than with ordinary invasive and in situ squamous carcinomas of the larynx. Nevertheless, the treatment is effective and provides an appropriate option for laryngeal conservation, especially in advanced lesions where total laryngectomy may be the only treatment alternative. Surgical salvage of radiation failures contributes to very high rates of cure for verrucous carcinoma of the larynx. Anaplastic transformation of cases treated with radiotherapy was not observed in any case in this series. PMID- 7790247 TI - The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. AB - PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10 , and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking. PMID- 7790248 TI - Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation. AB - PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate. PMID- 7790249 TI - The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. AB - PURPOSE: Current methods to clinically define head and neck tumor bulk are qualitative and imprecise. Although the American Joint Committee on Cancer (AJCC) staging system is important for this purpose, limitations exist. This study will investigate the prognostic value of computed tomography (CT) derived tumor volume measurements in comparison to AJCC stage and other significant variables. MATERIALS AND METHODS: Seventy-six patients with advanced head and neck squamous cell carcinoma were treated with concomitant boost accelerated superfractionated irradiation. Doses ranged from 68.4-73.8 Gy (median 70.2 Gy). Good quality pretherapy CT scans were available in 51 patients. Total tumor volume (TTV) estimates were derived from these scans using digital integration of primary tumor and metastatic lymphadenopathy. Actuarial and multivariate statistical techniques were applied to analyze local control. RESULTS: Thirty-six-month local control was 63%. TTV ranged from 5-196 cm3 (median 35 cm3) for all cases, 5-142 cm3 (median 17 cm3) for those controlled, and 16-196 cm3 (median 47 cm3) for local failures. There was a significant increase in failures above 35 cm3. Univariate analysis found that TTV, T-stage, N-stage, and primary site were each significant prognostic variables. Local control for TTV < or = 35 cm3 was 92% at 36 months vs. 34% for TTV > 35 cm3 (p = 0.0001). Multivariate analysis, however, found that TTV, primary site, and sex were important as independent variables; T and N stage were not independently significant unless TTV was removed from the model. CONCLUSIONS: This study demonstrates the prognostic significance of TTV in advanced carcinoma of the head and neck. This variable appears to be a more predictive than AJCC clinical stage. Quantitative tumor volume measurements may prove to be a useful parameter in future analyses of head and neck cancer. PMID- 7790250 TI - Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate. 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 late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. 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 a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. RESULTS: The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. CONCLUSION: The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long. PMID- 7790251 TI - Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. AB - PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20 165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5 and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed. PMID- 7790253 TI - External irradiation of macroinvasive pituitary adenomas with telecobalt: a retrospective study with long-term follow-up in patients irradiated with doses mostly of between 40-45 Gy. AB - PURPOSE: Published dose recommendations for radiotherapy in patients with pituitary macroadenomas vary. Therefore, we retrospectively analyzed the results in our patients from the treatment period 1973-1992. METHODS AND MATERIALS: From a total of 89 patients with macroinvasive adenomas, 66 received radiation therapy immediately following subtotal surgical removal (combined treatment modality), and 22 were irradiated as primary treatment or after surgical recurrence. Only one patient was reirradiated. The surgical interventions have been performed by the same surgeon. For the majority of patients (79 out of 89) with a mean follow up of 8.1 years (0.5-19 years) the total tumor dose ranged between 40-45 Gy at a dose per fraction of 1.8-2.25 Gy. All patients had bilateral opposed fields with telecobalt. Eleven patients had an additional arc rotation. RESULTS: The 10-year progression-free survival for all 89 patients independent of treatment modality was 88.1%. The 10-year progression-free survival for patients treated by surgery and adjuvant radiation therapy (40-45 Gy at 1.8-2.25 Gy, 60 out of 79) was 90.3%, and for radiation therapy alone (40-45 Gy at 1.8-2.25 Gy, 19 out of 79), 100% (p = 0.32). The prognostic factors for progression-free survival were the subtype of adenoma, the presence of visual symptoms at the time of diagnosis, the suprasellar extension, and the initial hormone levels. The presence of infiltration of adenoma cells in the basal dura or in the mucosa of the sinus sphenoidalis do not represent prognostic factors showing the special biological behavior of pituitary adenomas. Signs of x-ray-induced cerebral necrosis have not been observed in any patient. Long-term visual complications developed in four patients. This could be due to scar formation in the treated region, which can compress the optic nerve and provoke disturbance similar to an empty-sella syndrome. The latter occurred prevalently years after treatment, even though surgical methods of sellar plugging were used. The incidence of hypopituitarism after combined treatment modality at time of last follow-up (irradiated between 40-45 Gy at 1.8-2.25 Gy) was low (36%, 21 out of 60). CONCLUSION: In patients with pituitary macroadenomas, radiotherapy with a total dose of 40-45 Gy at 1.8 2.25 Gy per fraction resulted in a high local tumor control without serious morbidity. PMID- 7790252 TI - Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation. AB - PURPOSE: To determine the risk of, and risk factors for, developing cataracts after bone marrow transplantation. METHODS AND MATERIALS: Four hundred and ninety two adults who underwent bone marrow transplantation in Seattle were followed for 2 to 18 (median, 6) years. Before transplantation, patients received a preparative regimen of chemotherapy plus total body irradiation (TBI) (n = 407) or chemotherapy alone, without TBI (n = 85). TBI was administered in a single dose of 10 Gy (n = 74) or in fractionated doses totaling 12-15.75 Gy (n = 333). The risk of cataracts was determined for groups of patients with respect to the type of preparative regimen received and other pretransplant and posttransplant variables. RESULTS: One hundred and fifty-nine patients (32%) developed cataracts between 0.5 to 11 (median, 2.3) years after transplantation. The probability of cataracts at 11 years after transplantation was 85%, 50%, 34%, and 19% for patients receiving 10 Gy of single-dose TBI, > 12 Gy fractionated TBI, 12 Gy fractionated TBI, and no TBI, respectively (p < 0.0001). Among those developing cataracts, the severity was greater in patients after single-dose TBI (59% probability of surgical extraction) than after > 12 Gy fractionated TBI, 12 Gy fractionated TBI, or no TBI (33%, 22% and 23%, respectively). Patients given corticosteroids after transplant had a higher probability of cataracts (45%) than those without steroids (38%) (p < 0.0001). In a proportional hazards regression model, the variables that were correlated with an increased probability of cataracts were single-dose TBI (relative risk (RR) = 2.46) and steroid therapy (RR = 2.34), while a decreased probability of cataracts was correlated with a nonTBI preparative regimen (RR = 0.41). The yearly hazard of developing cataracts in recipients of single-dose TBI was highest during the third year after transplantation, while in recipients of fractionated TBI, the hazard was distributed among years one through seven. The probability of cataracts in all groups reached a plateau at 7 years after transplantation, after which the development of cataracts was extremely unlikely. CONCLUSION: TBI is the major risk factor for developing cataracts after BMT. Single-dose TBI results in the highest risk of cataracts. However, the risk of cataracts in recipients of fractionated-TBI is significantly higher than in patients who receive no TBI. In addition to TBI, steroid therapy is an independent risk factor for cataracts after BMT. PMID- 7790254 TI - Induction of cisplatinum sensitivity without alteration in radiation sensitivity by fractionated radiation treatment of a human laryngeal squamous cell carcinoma cell line. AB - PURPOSE: To determine if fractionated radiation treatment can alter cisplatinum sensitivity of a human laryngeal squamous carcinoma cell line. METHODS AND MATERIALS: Human squamous carcinoma cells, both previously untreated, as well as survivors of fractionated radiation therapy, were tested in vitro for their sensitivity to gamma radiation and cisplatinum. Fractionated gamma radiation was delivered in 14 or 10 daily fractions of 2 Gy. The cell line, cSCC-20, was derived from an untreated primary human laryngeal carcinoma. RESULTS: The human laryngeal squamous cell carcinoma cell line, cSCC-20, was demonstrated to have heterogeneous subpopulations with respect to cisplatinum sensitivity. No variation in radiation sensitivity was seen among subpopulations of varying cisplatinum sensitivity. The cells were relatively radioresistant (Do = 2.5 Gy). Fractionated radiation treatments of the parent cell line (14 fractions, 14 days, 2 Gy/fraction) or a cisplatinum sensitive subline (10 fractions, 12 days, 2 Gy/fraction) induced cisplatinum sensitivity (factor of 1.3 to 1.4) in the surviving cells. CONCLUSION: Fractionated radiation treatment of human squamous carcinoma cells in vitro induced sensitivity to cisplatinum without concomitant alteration in radiation sensitivity. PMID- 7790256 TI - PO2 in irradiated versus nonirradiated tumors of mice breathing oxygen at normal and elevated pressure. AB - PURPOSE: To determine if prior tumor irradiation influences tumor pO2 changes in mice breathing oxygen (100%) at normal and elevated pressure. METHODS AND MATERIALS: Single-point pO2 measurements were performed in nonirradiated and previously irradiated (72 h) isotransplanted MCaIV tumors in C3H/Sed mice. Continuous recordings were performed at the same tumor locus under air breathing, followed by 100% oxygen and oxygen at three atmospheres pressure. Following decompression and induction of pentobarbital anesthesia, the procedure was repeated at the same locus. Six nonirradiated and five irradiated tumors were evaluated under the three gas breathing conditions +/- anesthesia. RESULTS: The mean, median, and range of pO2 values did not differ under air-breathing conditions in the nonirradiated vs. previously irradiated tumors. However, prior irradiation substantially enhanced the tumor pO2 increase when the inspired gas phase was switched from air to 100% oxygen at 1 or 3 atmospheres pressure. In four of six nonirradiated tumors, 100% oxygen breathing resulted in a pO2 increase of < 4 mmHg; in the irradiated tumors, the minimum increase was 16 mmHg. Pentobarbital anesthesia did not significantly influence the results obtained. CONCLUSION: These data indicate that the efficacy of oxygen breathing increases during tumor treatment, and suggests that oxygen breathing is a simple nontoxic method for reducing or eliminating radiobiologic hypoxia during therapy. PMID- 7790255 TI - Slowing proliferation in head and neck tumors: in vitro growth inhibitory effects of the polyamine analog BE-4-4-4-4 in human squamous cell carcinomas. AB - PURPOSE: These preclinical studies were carried out to examine the potential of the antiproliferative polyamine analog 1,19-bis-(ethylamino)-5,10,15 triazanonadecane (BE-4-4-4-4) to serve as a therapy adjuvant to radiation for patients with rapidly dividing tumors of the head and neck (H&N). METHODS AND MATERIALS: Cytostatic and cytotoxic effects of this polyamine analog were investigated in three squamous cell carcinoma (SCC) cell lines derived from human H&N tumors. RESULTS: Growth inhibition was achieved in all cell lines within 3-4 days of continuous 10 microM drug exposure, and inhibition of cell cycle proliferation kinetics was confirmed via flow cytometry. Cytotoxicity was pronounced (3-4 log cell kill) in the SCC-38 and SCC-4Y cell lines with continuous 10 microM analog exposure over 5 days, and was minimal in the SCC-13Y cell line. No demonstrable effect of BE-4-4-4-4 on single dose radiation survival was identified in any SCC cell line. Ornithine decarboxylase (ODC) activity was rapidly inhibited (1-2 h) following 10 microM BE-4-4-4-4 exposure in all SCC cell lines (approximately 90%), whereas identical exposure to 10 microM difluoromethylornithine (DFMO) induced animal ODC inhibition (approximately 10%). Dose-dependent depletion of endogenous polyamines (putrescine, spermidine, spermine) was achieved in all SCC cell lines following 1 microM and 10 microM BE 4-4-4-4 exposures. Difluoromethylornithine was significantly less potent than BE 4-4-4-4 in its capacity to deplete endogenous polyamines, with no measureable depletion of spermine pools even with 5 mM x 48 h DFMO exposures. CONCLUSIONS: These data evaluate cytostatic and cytotoxic properties of the polyamine analog BE-4-4-4-4 in human SCCs, and suggest a role for investigation of such agents as an adjuvant to radiation in the therapeutic approach to rapidly dividing human tumors such as those that occur in the H&N. PMID- 7790257 TI - Blood-spinal cord barrier function and morphometry after single doses of x-rays in rat spinal cord. AB - PURPOSE: The effects of irradiation on blood-spinal cord barrier (BSCB) function and ultrastructure were evaluated using a rat spinal cord model. METHODS AND MATERIALS: Rats received a single dose of 25 Gy to the cervical spinal cord (C2 T2). At various times following irradiation and before the onset of paralysis, BSCB function was assessed using horseradish peroxidase (HRP) as a vascular tracer, and barrier-related structural changes in the capillaries were evaluated using morphometric techniques. RESULTS: Focal extravasation of HRP was seen at 93 days after irradiation, and extensive extravasation was apparent by 114 days in white matter, but not in gray matter. At 93 days, pathologic changes apparent by light microscopy were very minor in the white matter of the irradiated segment. By 107 days, myelin beading, Wallerian degeneration, edema, and histiocytes were apparent in white matter, and these features became increasingly prominent over the following weeks. No noteworthy changes were seen in gray matter at these times. Electron microscopic examination showed that, during the first 93 days following irradiation, more than half of the endothelial cells in white matter had disappeared (p < 0.05). In terms of the putative vascular pores, no abnormalities in endothelial junctions (the presumed small pore) were found, but there was an increase in the density of endothelial vesicles (a putative form of the large pore) in irradiated white matter (p < 0.001), but not in gray matter. Pericytes, thought to act as a second line of defence in the blood-brain barrier, increased in size but not in number in the irradiated white matter of the spinal cord. CONCLUSION: We suggest that radiation damage to endothelial cells, which form the BSCB prior to the onset of neurological deficit, may play an important role in the pathogenesis of white matter necrosis. PMID- 7790258 TI - Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer. AB - PURPOSE: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. METHODS AND MATERIALS: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. RESULTS: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. CONCLUSIONS: Radiobiological analysis, which incorporates simple models of metastatic spread, emphasizes the importance of the total body irradiation component in a targeting/total body irradiation combination strategy. However, the analysis favors a larger targeting component than is used in clinical practice at present. A cautious escalation of the 131I mIBG component in the combination treatment of advanced neuroblastoma appears justified. PMID- 7790259 TI - Tissue compensation using dynamic collimation on a linear accelerator. AB - PURPOSE: The availability of computer-controlled collimators on some accelerators has led to techniques for dynamic beam modification, mainly to simulate beam wedge filters. This work addresses the practical aspects of dynamic tissue compensation in one dimension using available treatment-planning software. METHODS AND MATERIALS: Data derived from the treatment-planning program is used with an iterative calculational routine to determine the monitor unit settings needed for the collimator-controlling computer. The method was first tested by simulating a 60 degrees physical wedge. Further studies were carried out on a specially fabricated plastic phantom that modeled the sagittal contour of the upper torso, neck, and lower head regions. RESULTS: Dynamic wedge point doses generated by the planning program agreed within 1% with the values directly measured in a polystyrene phantom. In the patient phantom, dynamic collimation achieved calculated dose uniformity within 0.5% in a reference plane near the phantom midline. A comparison of computer-generated and measured point doses in this case showed agreement within 3%. CONCLUSIONS: Dynamic collimation can provide effective compensation for contours that vary primarily along one direction. A conventional treatment-planning program can be used to plan dynamic collimation and deliver a prescribed dose with reliable accuracy. PMID- 7790260 TI - Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study. AB - PURPOSE: Since 1985, the University of Minnesota Hospital and Clinic has investigated the efficacy and safety of 8 MHz radiofrequency (RF) capacitive hyperthermia using the Thermotron RF-8. This study reports the thermometric and clinical results of 119 patients treated with RF hyperthermia in combination with radiotherapy (RT). METHODS AND MATERIALS: Of 119 patients, 69 received high-dose RT and 50 patients received low-dose RT because of previous irradiation to the treatment site. The most common anatomic sites treated were within the pelvic cavity or head and neck area. Thirty-three percent and 24% of tumors treated were > 7 cm and > 10 cm in largest diameter, respectively. Forty percent of the patients had deep-seated tumors (depth > 6 cm). Hyperthermia was given as soon as possible after RT twice weekly, allowing at least 72 h between treatments. The objective was to raise intratumoral temperatures to 42-43 degrees C or above for 30-50 min while keeping normal tissue temperatures below 40-41 degrees C. RESULTS: Of 119 patients, 40% achieved a Tmax tumor temperature of > 42 degrees C and 40% achieved 40-42 degrees C Tmax. Higher Tmax) tumor temperatures were observed as tumor size increased. Tumors > 10 cm in largest diameter had a Tmax of 42.2 degrees C. Tumor depth was not a significant factor for the tumor temperatures achieved. Of 119 patients, 11% achieved complete response and 38% achieved partial response. Of the no-response patients, 34% had symptomatic palliation and 15% had stable disease for at least 12 months after treatment. We were able to treat tumors of patients with subcutaneous fat as thick as 3 cm by precooling the fat for 20 min with 10-15 degrees C saline-filled boluses prior to the initiation of heating. During treatment, 60% of patients complained of varying degrees of pain and 19% had pain that was a factor in limiting treatment. Vital signs were relatively stable and not a factor in limiting treatment. CONCLUSION: The Thermotron RF-8 is a useful hyperthermia device that can raise tumor temperatures to a therapeutic level (i.e., 42 degrees C) in a significant proportion of patients with superficial, subsurface, and deep-seated tumors, with minimal adverse effects, complications, and systemic stress. Further clinical studies using improved thermometry systems are warranted. PMID- 7790263 TI - Split-course accelerated therapy in head and neck cancer: an analysis of toxicity. AB - PURPOSE: To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. METHODS AND MATERIALS: SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. RESULTS: Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). CONCLUSION: Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered. PMID- 7790262 TI - Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies. AB - PURPOSE: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. METHODS AND MATERIALS: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT+PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT+E subgroup). RESULTS: The median overall survival was 19 months for the CRT group and 15 months for the CRT+PE group. For the CRT+E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT+PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3 year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT+PE group. Of the 12 patients who underwent esophagectomy (CRT+E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of 20 and 100 months, respectively. Treatment-related mortality was 0 out of 11 in the CRT group and 2 out of 24 in the CRT+PE group. Dysphagia relief was similar in the CRT group vs. the CRT+E subgroup; however, a greater percentage of patients treated with chemoradiation alone had normal long term swallowing function when compared to those patients also undergoing esophagectomy (100% vs. 73%). CONCLUSION: High-dose chemoradiation alone appears to provide similar survival and relief of dysphagia compared with high-dose chemoradiation followed by esophagectomy for patients with potentially resectable esophageal adenocarcinoma. Local failure may be higher in patients undergoing chemoradiation compared to chemoradiation followed by esophagectomy, but surgical salvage is possible, thus providing similar overall local control. However, because of the small number of patients in each group, these treatment modalities need to be further evaluated in a prospective randomized Phase III study. PMID- 7790261 TI - Very accelerated radiation therapy: preliminary results in locally unresectable head and neck carcinomas. AB - PURPOSE: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. RESULTS: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco regional control rate was 59% (95% confidence interval, 45-73%). CONCLUSIONS: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer. PMID- 7790264 TI - Outcome following radiation treatment for high-risk pigmented villonodular synovitis. AB - PURPOSE: Pigmented villonodular synovitis (PVNS) is a rare proliferative process involving synovial membranes. It has a variable course, and while usually benign, may be destructive, resulting in major symptoms and loss of function leading to amputation. Optimum treatment is not always clear, and little information exists with respect to the role of radiotherapy. The purpose was to review our experience with radiotherapy in cases at high risk for recurrence with functional loss including instances where amputation was the sole alternative for symptomatic disease. METHODS AND MATERIALS: The records of all patients registered between 1972 and 1992 with a diagnosis of PVNS were identified (21 cases). The records of 14 cases who received radiotherapy after referral were reviewed retrospectively for demographic information, radiotherapy treatment parameters, and tumor outcome. RESULTS: All cases had confirmation of pathologic diagnosis. Six patients had primary and eight had recurrent disease (with a mean of 2.5 prior surgical procedures). All cases had both intra- and extraarticular disease and, without exception, the poorer prognosis diffuse subtype of the disease. The majority had one or more additional risk factors including skin, bone, tendon, neurovascular, or muscle group extension. With a mean follow-up time of 69 months (range 13-250 months), only one patient has shown persistence of disease. With the exception of that single case, all those with measurable disease had obvious disease until at least 12 months and, subsequently, manifested complete responses. The single case was lost from the clinic after 8 months from the initiation of radiotherapy to a dose of 30 Gy in 15 fractions and had a palpable mass at the time. He subsequently was noted to have a persisting mass and an excisional biopsy 9 years later showed PVNS. He remains well 21 years after treatment with good function. Eleven patients enjoyed excellent or good function from the affected limb and three had fair function. All patients had greater use of limb than at the time of treatment. No patient required amputation, and none had evidence of serious radiotherapy complications. CONCLUSIONS: These results demonstrate that moderate dose radiotherapy is an effective modality in the treatment of a subset of cases with this rare condition. Its use has permitted avoidance of amputation in very advanced cases with acceptable function preservation. When treatment is indicated we currently recommend gross total removal of PVNS. This is followed by moderate dose radiotherapy (35 Gy in 15 fractions) for residual disease where salvage of subsequent recurrence may compromise function. PMID- 7790266 TI - Staging and follow-up of nasopharyngeal carcinoma: magnetic resonance imaging versus computerized tomography. AB - PURPOSE: To compare computerized tomography (CT) and magnetic resonance (MR) in relation to their accuracy in the staging of nasopharyngeal carcinoma (NPC); to compare CT and MR in postirradiation follow-up of NPC. METHODS AND MATERIALS: Staging: From 1985 to 1993, 53 patients affected with NPC were studied with MR and CT. All cases were biopsy-proved epithelial carcinoma. Plain and contrast enhanced CT scans were performed with third-generation scanners. Magnetic resonance were obtained with 0.5 and 1.5 Tesla units in sagittal, axial, and coronal planes. Computerized tomography was chosen as reference method and findings obtained with MR were compared to those obtained with CT. FOLLOW-UP: From 1985 to 1993, 53 patients irradiated with radical intent were followed up with both CT and MR; 71 examinations were performed in all. The baseline follow up scan was performed, in general, no sooner than 2 months after the end of radiotherapy. All patients were submitted to unlimited clinical follow-up. RESULTS: Staging: Magnetic resonance showed retropharyngeal adenopathies in 6 of 14 cases in which oropharyngeal involvement had been reported after CT; in 3 other patients, adenopathies were recognized on MR, while primary extent to parapharyngeal space had been diagnosed on CT initially. Infiltration of long muscles of the neck was revealed with MR in 14 cases. On the other hand, CT showed bone invasion in 12 patients vs. 8 on MR. Upstaging to T4 occurred in four cases on the basis of CT; no upstaging occurred after MR. FOLLOW-UP: Findings on CT were uncertain in 10 out of 53 patients, disease recurrence was excluded by MR in nine cases, whereas progressive disease was confirmed in one patient. CONCLUSION: Staging: Our series shows that either CT and MR can provide essential information in the staging of NPC. Magnetic resonance, however, seems to provide the most detailed imaging of soft tissue invasion outside the nasopharynx and of retropharyngeal node involvement. Nonetheless, its limitations in evaluating bone details suggest that CT should be always performed when the status of base of skull is uncertain on MR. General reasons and our data indicate that CT can still be considered a valuable tool in routine NPC staging. Follow up: Magnetic resonance may be the modality of choice because it seems to solve, more often than CT, the problems of differentiation between postradiation changes and recurring tumor, apart from those cases showing subtle bone erosions on initial CT scan. PMID- 7790265 TI - Evaluation of response to radiotherapy in head and neck cancer by positron emission tomography and [11C]methionine. AB - PURPOSE: To evaluate the usefulness of positron emission tomography (PET) and L [methyl-11C]methionine in assessing treatment response to radiotherapy in head and neck cancer. METHODS AND MATERIALS: Fifteen patients with head and neck cancer (13 with squamous cell carcinoma, 1 with adenocystic carcinoma, and 1 with paranasal plasmocytoma) underwent a PET study with [11C]-methionine both before and after preoperative radiotherapy to the total tumor dose of 61-73 Gy. Twelve primary and 12 metastatic tumor sites were within the field of view. Nineteen of the 24 tumor sites were surgically explored after radiotherapy, and the tumor standardized uptake values (SUVs) of [11C]methionine were compared with histological findings. RESULTS: All 24 malignant lesions were detectable in the pretreatment study. In all but one case, the tumor SUV decreased after radiotherapy. The median SUV of the tumor site was smaller (1.9, range, 1.3-3.1, n = 7) in cases with histologically verified complete response than in cases with persistent cancer (median 4.1, range, 2.8-7.6, n = 12, p = 0.0008). A complete histological response was verified in none of the 9 cases with a postirradiation SUV larger than the median (3.1), whereas 7 of the 10 cases with a SUV of 3.1 or smaller had complete response (p = 0.003). The preirradiation uptake of [11C]methionine in tumors did not have significant association with histological response (p = 0.45). The PET findings correlated well with follow-up data in five cases with unoperated tumor sites. The [11C]methionine uptake of the submandibular salivary glands decreased after radiotherapy (p = 0.04). CONCLUSION: PET with [11C]methionine as a tracer may be useful in assessing response to radiotherapy in head and neck cancer. High uptake of [11C]methionine in the postirradiation scan suggests the presence of persistent disease. PMID- 7790267 TI - Arytenoid sparing during irradiation of early stage vocal cord cancer. AB - PURPOSE: Optimal position of the posterior field border when irradiating early stage vocal cord cancer is controversial. Several experts recommend moving the posterior field border 5-15 mm anteriorly after 50-60 Gy to decrease the chance of arytenoid edema. This article will evaluate the effect of field position on arytenoid dose. METHODS AND MATERIALS: 5 x 5 cm opposed lateral fields centered on the glottis were set up on a patient with typical anatomy. Isodose profiles were obtained with equally weighted 6 MV photon beams attenuated with 15 degree wedge filters using contours from an axial CT scan. Profiles with the posterior field border overlaying, 5, and 10 mm posterior to the posterior edge of the thyroid cartilage are presented. RESULTS: With the posterior field border 10 mm posterior to the thyroid cartilage, the arytenoids are included in the 95% isodose volume. Reducing the field by 5 mm has no significant effect on the position of the 95 and 90% isodose lines relative to the arytenoids. A field reduction of 10 mm places the arytenoids in the beam penumbra and leaves approximately 10 mm between the 95% isodose line and the midpoint of the true vocal cord. CONCLUSION: To achieve a significant dose differential between the arytenoids and the anterior portion of the vocal cord when using opposed lateral 6 MV photon beams the posterior field border must be at, or anterior to, the posterior edge of the thyroid cartilage. In view of the excellent results reported from institutions that include the arytenoids in the high-dose volume throughout treatment, it would seem appropriate to limit the use of arytenoid sparing techniques to patients in whom there is no ambiguity about tumor location and in whom the treatment setup is very reproducible. PMID- 7790269 TI - Simulation accuracy in radiotherapy for maxillary sinus tumors. AB - PURPOSE: To evaluate the accuracy and clinical importance of beam positioning during simulation of radiation treatment for tumors in the maxillary sinus. METHODS AND MATERIALS: Five patients were prepared as if they were to be treated for a maxillary sinus tumor. A three-beam computed tomography (CT) scan-based computer plan was made for each patient. The location of the central beam axis of each beam was measured, relative to bony anatomical structures. A simulation was performed using the bony references to position the radiation beams during simulation. After this, the simulation procedure was repeated by the use of a noninvasive external localization frame with a known accuracy and reproducibility within 2 mm margins. RESULTS: When defining the clinical target volume as the known tumor with a 1 cm margin, three out of five patients would suffer a partial geographical miss throughout the entire radiation treatment due to erroneous beam positioning at the simulation stage when using bony structures as a guide for beam positioning. The influence of these errors is analyzed as normal tissue complication and tumor control probabilities. CONCLUSION: When defining a planning target volume, one should consider a margin to correct for possible simulation errors. We advise the use of objective, external (and thus nonanatomical) landmarks as a reference during simulation to reduce this extra margin to a minimum. In case of simulation, using bony structures as a reference, an additional margin should be entered, depending on the simulation accuracy that can be obtained. PMID- 7790268 TI - A method for delivering accurate and uniform radiation dosages to the head and neck with asymmetric collimators and a single isocenter. AB - PURPOSE: To investigate the use of asymmetric collimators and a single isocenter for delivering a uniform, accurate dose of radiation to the head, neck, and supraclavicular lymph nodes. METHODS AND MATERIALS: A linear accelerator with a pair of asymmetric collimators is required for this technique. An isocenter was placed at the junction of the lateral head and neck fields and the anterior supraclavicular field. The asymmetric collimators were set longitudinally, by collimator rotation if necessary. The collimators split the radiation beam to all portals. Dose uniformity was measured at the junction with films in solid-water phantoms. RESULTS: Film dosimetry showed a uniform dose at the junction without hot or cold regions. A digital display tolerance of +/- 1.0 mm for a field size maintained an acceptable uniform dose (+/- 5% dose variation) at the junction. The single isocenter and asymmetric collimators reduced field setup time by half. No table rotation was required to match fields. CONCLUSION: The asymmetric collimators lead to easy and accurate patient setup. The absence of the trapezoid effect resulted in the complete coverage of the submandibular and cervical nodes without any hot spots. PMID- 7790271 TI - Dose-volume histogram analysis of techniques for irradiating pituitary adenomas. AB - PURPOSE: Three-dimensional treatment planning was performed to evaluate three standard coplanar irradiation techniques (two-field parallel-opposed, three field, and 110 degrees bilateral arcs), the 330 degrees single rotational arc, and a four noncoplanar arc technique for the treatment of pituitary adenomas. We sought to identify the optimal technique for minimizing the dose delivered to the normal tissues around the pituitary gland. METHODS AND MATERIALS: Contours of the pituitary tumor and normal tissues were traced onto computed axial tomography (CT) scans and reconstructed in three dimensions using a three-dimensional planning system. A total dose of 45 Gy was delivered to the pituitary lesion with the five techniques using 6 MV and 18 MV photons, and dose-volume histograms were generated. RESULTS: The 18 MV photons delivered a lower dose to the temporal lobe than did the 6 MV photons in the two-field technique, but this advantage was not evident for the other techniques. The three-field technique improved dose distribution throughout the temporal lobes with low doses being delivered to the frontal lobe. The bilateral arc and the 330 degrees arc techniques were superior to stationary two- and three-fields techniques for sparing the temporal lobes. The four noncoplanar arc technique delivered less doses to the temporal and frontal lobes than did the other techniques. However, the lens dose (3.6 Gy/25 fractions) was higher compared to the other techniques. CONCLUSION: Analysis of the dose-volume histograms shows the various dosimetric advantages and disadvantages of the five techniques. Based upon individual considerations, including the patient's age and medical history, one can decide the optimal technique for treatment. PMID- 7790270 TI - Fetal dose estimates for radiotherapy of brain tumors during pregnancy. AB - PURPOSE: To determine clinically the fetal dose from irradiation of brain tumors during pregnancy and to quantitate the components of fetal dose using phantom measurements. METHODS AND MATERIALS: Two patients received radiotherapy during pregnancy for malignant brain tumors. Case 1 was treated with opposed lateral blocked 10 x 15 cm fields and case 2 with 6 x 6 cm bicoronal wedged arcs, using 6 MV photons. Fetal dose was measured clinically and confirmed with phantom measurements using thermoluminescent dosimeters (TLDs). Further phantom measurements quantitated the components of scattered dose. RESULTS: For case 1, both clinical and phantom measurements estimated fetal dose to be 0.09% of the tumor dose, corresponding to a total fetal dose of 0.06 Gy for a tumor dose of 68.0 Gy. Phantom measurements estimated that internal scatter contributed 20% of the fetal dose, leakage 20%, collimator scatter 33%, and block scatter 27%. For case 2, clinical and phantom measurements estimated fetal dose to be 0.04% of the tumor dose, corresponding to a total fetal dose of 0.03 Gy for a tumor dose of 78.0 Gy. Leakage contributed 74% of the fetal dose, internal scatter 13%, collimator scatter 9%, and wedge scatter 4%. CONCLUSIONS: When indicated, brain tumors may be irradiated to high dose during pregnancy resulting in fetal exposure < 0.10 Gy, conferring an increased but acceptable risk of leukemia in the child, but no other deleterious effects to the fetus after the fourth week of gestation. For our particular field arrangements and linear accelerators, internal scatter contributed a small component of fetal dose compared to leakage and scatter from the collimators and blocks, and 18 MV photons resulted in a higher estimated fetal dose than 6 MV photons due to increased leakage and collimator scatter. These findings are not universal, but clinical and phantom TLD measurements estimate fetal dose accurately for energies < 10 MV and should be taken for each pregnant patient considered for treatment to confirm and document acceptable dose. PMID- 7790272 TI - Testicular doses in definitive radiation therapy for localized prostate cancer. AB - PURPOSE: To measure the dose received by the unshielded testes during a conventional course of 18 MV photon radiotherapy for localized prostate cancer and to identify the factors influencing it. METHODS AND MATERIALS: For each of four patients, a wax block containing thermoluminescent chips was attached to the posterior aspect of the scrotum in close proximity to the testes on each day of treatment during a full course of radical radiotherapy, and dose measurements were obtained. The distances between the thermoluminescent chips and the beam edge were verified by measurement from port films. The accuracy of the in vivo measurements and the factors influencing the testis dose were studied using a phantom arrangement. Six factors were considered: (a) the relative contributions from primary and scattered radiation, (b) the amount of buildup required for the thermoluminescent chips that monitored testis dose, (c) the position of the testes within the scrotum, (d) field size, (e) distance from the field lower border, and (f) the effect of port films. RESULTS: Median daily doses to the testes in four patients ranged from 5 to 7 cGy. Daily doses for the four patients ranged from 4 to 14 cGy. The total dose to the testes over the full course of therapy ranged from 1.8 to 2.4 Gy. The daily dose depended primarily on the distance from the field lower border. This was increased by approximately 2.5 cGy when a 6 MV port film was taken. The relative contributions from primary and scattered radiation were found to be similar. Dose measurements at the posterior aspect of the scrotum overestimated the testis dose by approximately 15%. CONCLUSION: The most important factors influencing the dose received by the testis are the distance from the testes to the field lower border and the occasion of a port film. A knowledge of the number of port films and the average distance from the field lower border to the testes allows a reasonable prediction of testes dose without daily measurement. PMID- 7790273 TI - Quality control of inhomogeneity correction algorithms used in treatment planning systems. AB - PURPOSE: This quality control program has been carried out under the auspices of S.F.P.H. (Societe Francaise des Physiciens d'Hopital), to evaluate the performances of radiotherapy treatment planning systems (RTPS) used by different institutions. The aim of this Quality Assurance Programme was: (a) to set up a methodology to assess globally the capability of a given system to perform inhomogeneity corrections in the irradiated medium with external photon beams; (b) to analyze the limitations of the algorithms presently used and especially the two-dimensional (2D) dose calculation possibilities; (c) to check, on a number of systems in clinical use, the validity of the method and the variation of the results as compared to measurements used as reference. METHODS AND MATERIALS: Phantom (lung equivalent material placed into polystyrene) measurements, using cobalt-60 radiation, were carried out by the authors. The phantoms were circulated among the participating institutes to be scanned, and used as input to the treatment planning computer. RESULTS: Ten systems were tested in this study, using seven different inhomogeneity correction algorithms implemented in nine different TPS; four of these algorithms are used in a pixel by pixel basis and five of them in a contour basis. Significant discrepancies or inconsistencies have been observed even for sophisticated models supposed to be mostly accurate. CONCLUSION: The proposed tests and the experimental data provided are very useful as part of a quality-control program. They should be included in the initial extensive validation of TPS before starting clinical use, and should be repeated at regular intervals and at each updating of the program. They have the merit of including the whole procedure, from patient data acquisition to dose distribution printout. PMID- 7790274 TI - Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects. AB - Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoid lineage tumor related to the Epstein Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic agressiveness is the source of most disease related demises, because radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Difference in the staying systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and squamous cell carcinoma (SCC) of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin-based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above-mentioned aspects of this fascinating nosologic entity, our own experience, both in metastatic and locoregional disease patients is analyzed. PMID- 7790275 TI - Fast neutron radiotherapy: where have we been and where are we going? The jury is still out--regarding Maor et al., IJROBP 32:599-604; 1995. PMID- 7790276 TI - Hypoxic cell radiosensitizers: the end of an era? Regarding Lee et al., IJROBP 32:567-576; 1995. PMID- 7790277 TI - Interfraction interval and dose-response in RTOG trials--regarding Fu et al., IJROBP 32:577-588; 1995. PMID- 7790278 TI - Accelerated fractionation: the do's and don'ts--regarding Fu et al., Bourhis et al. and Delaney et al., IJROBP 32:589-597; 1995. PMID- 7790279 TI - In response to Dr. Rich--IJROBP 32:547-548; 1995. PMID- 7790281 TI - Stage D1 prostate cancer--is radiotherapy and early hormonal therapy equivalent to radical prostatectomy, radiotherapy, and early hormonal therapy? regarding Sands et al., IJROBP 31:13-19; 1995. PMID- 7790280 TI - Re: "Waiting for radiotherapy in Ontario" by Mackillop et al. and "in response to 'waiting..."' by L.W. Brady, IJROBP 30; 1994. PMID- 7790282 TI - The Sr-89 bracelet. PMID- 7790283 TI - Regarding Herman et al., IJROBP 17:1273-1278; 1989. PMID- 7790284 TI - Detecting simulated amnesia with event-related brain potentials. AB - Two experiments were done in which groups of normal college undergraduate subjects were instructed to simulate autobiographical amnesia related to head injury. The subjects were tested for autobiographical knowledge with pencil-and paper recall and recognition tasks, and on another day, with recognition tasks in which event-related potentials were recorded in response to the same autobiographical items, this time presented on a display screen. In the first study, three Event-Related Potential (ERP) block types were utilized: 1) a block in which the subject's birthdate was an oddball with p = 0.11 and other dates (not relevant to the subject) had p = 0.89, 2) a block in which phone numbers were used as stimuli, and 3) a block in which (mothers' maiden) names were used as stimuli. Only birthdate blocks were used in the second study. A P300 ERP was seen in response to rare, personally relevant items. In both studies, the main effect of stimulus type (personally relevant versus not personally relevant) on P300 amplitude was significant (p < 0.0001) and there was no main effect of block type in the first study. Under a sophisticated malingering instruction set, about 15% of the items were correctly recalled and about 50% were correctly recognized by simulators in pencil-and-paper tests. Under a naive malingering instruction set, most simulating subjects failed to recall and recognize autobiographical items. In the first study, an arbitrarily but a priori derived discrimination criterion based on a subject's average P300 amplitude afforded 92% correct discrimination of simulating individual subjects for birthdates and phone numbers. The value was 77% for mothers' maiden names. The same criterion applied to the single birthdate block in the second study yielded 93% correct discrimination. The results suggest the P300 may be useful in detection of malingered amnesia. PMID- 7790285 TI - Baroreflex sensitivity during noxious stimulation in vasovagal reactors to blood donation. AB - Baroreflex sensitivity was assessed at rest and during constrictive pain in healthy males with and without a history of vasovagal reactions to blood donation. Continuous recordings of cardiac inter-beat interval and finger arterial pressure were obtained at rest and during repeated presentations of constrictive thigh-cuff stimulation. Baroreflex sensitivity (in msec/mm Hg) was computed according to the spontaneous sequence analysis method. Results indicated that vasovagal reactors exhibited significantly lower descending baroreflex sensitivity across all periods, and significantly lower ascending baroreflex sensitivity at rest. Baseline differences in ascending baroreflex sensitivity were eliminated during thigh-cuff stimulation, as vasovagal reactors exhibited increases in ascending baroreflex sensitivity while non-reactors exhibited decreases. These findings suggest that susceptibility to vasovagal reactions may be associated with individual differences in baroreflex sensitivity. PMID- 7790286 TI - Electroencephalographic coherences discriminate between children with different pedagogical evaluation. AB - The relationship of reading-writing ability and EEG coherences was studied in 84 subjects from two age groups 7.0-8.9 and 9-11.2 years old. All children were divided into three groups according to their performance on a pedagogical test: ped1, normal children; ped2, children with mild problems; ped3, children with reading-writing disability. The following results were obtained: in general, children showed higher coherences in groups with poor performance in the delta, theta and beta bands. In the alpha band, higher coherence values were related to better performance. The exceptions to this general pattern were rare. Group ped2 had higher coherences in delta, theta and alpha bands than ped1 and ped3, in left temporal leads. In older children the same tendency was observed, but group differences in the theta, alpha and beta bands were few. In this age range, the significant group differences were almost all interhemispheric coherences. The discriminant analysis that classified subjects by their coherence values gave very good results, fact that demonstrates, that EEG coherence is a highly sensitive measurement indicating not only the existence of a reading-writing problem, but also the degree of its severity. PMID- 7790287 TI - Changes in visual fixation and saccadic eye movements in Alzheimer's disease. AB - Visual fixation and saccadic eye movements were assessed in 31 mild to moderately demented patients with probable Alzheimer's disease (AD) and 31 age- and education-matched nondemented elderly control subjects. Seventeen AD and 17 matched control subjects were reassessed after a 9-month interval. On a fixation task, duration of fixation and number of intrusive saccades were not different between groups at baseline or follow-up. Both AD patients and control subjects showed more intrusive saccades at follow-up than at baseline. AD patients showed increased latency to initiation of saccades at baseline and on follow-up. Amplitude and velocity of saccades were not different between groups at any visit. Changes in measures of fixation, but no saccade measure, correlated with changes in MMSE scores over testing sessions. These data suggest that fixation is more sensitive than are saccades to the progession of AD. PMID- 7790288 TI - Spontaneous conscious covert cognition states and brain electric spectral states in canonical correlations. AB - Correlations between subjective, conscious, spontaneous cognitions and EEG power spectral profiles were investigated in 20 normal volunteers (2 sessions each) during relaxation-drowsiness-sleep onset. Four-channel EEG (temporal-parietal and parietal-central, left and right) was continuously recorded. The subjects were prompted 15 times per session to give brief reports of their ongoing thoughts. The reports were rated on 23 scales, and the 16 seconds of EEG recording preceding the prompts were spectral analyzed. Canonical correlation analysis was applied to the data (23 cognition ratings and 124 EEG spectral values for each of the 538 prompts). Four of the 23 pairs of canonical EEG variables and cognition variables were significant (p < 0.016) with correlation coefficients ranging from 0.78 to 0.62. The four pairs of canonical variables showed distinctive features in EEG spectra and cognition styles. The results demonstrate ruleful correspondences between EEG states and spontaneous, conscious, covert, cognitive emotional states in a no-input, no-task, no-response paradigm. PMID- 7790289 TI - Electrocortical, autonomic, and subjective responses to rhythmic audio-visual stimulation. AB - The present study was designed to test the hypothesis that varying sensory input can affect mood, autonomic arousal, and electrocortical activity. Twenty right handed males were exposed to three rhythmic audio-visual stimulation programs, with either a high intensity and variety of stimuli (program H), a low stimulation (program L) or with a transient from high to low (program HL). Multichannel EEG, heart rate, and skin conductance were recorded continuously, and after each trial mood was rated on a bipolar adjective list. EEG data were subjected to FFT dipole approximation procedure, and dipole locations and field strength (Global Field Power) were analyzed for the frequency bands theta, alpha, and beta 1. Mood ratings clearly differed between programs H and HL, with highest values of arousal after H. Programs L and HL decreased autonomic arousal, whereas H induced deactivating as well as activating effects. Field strength of the alpha band decreased similarly during all programs. Dipole sources were located more to the left in the alpha band and more to the right in the beta 1 band during all programs as compared with baseline. Therefore, programs affected mood and autonomic variables differently, but not electrocortical variables. The higher activation of the right hemisphere during all programs is interpreted as an indication that audio-visual stimulation does induce changes in the brain, such as are commonly found in altered states of consciousness. PMID- 7790291 TI - Random number generation and the frontal cortex. PMID- 7790290 TI - Baroreceptor cortical effects, emotions and pain. AB - The specificity of baroreceptor-dependent inhibition of pain reactions to electrical stimuli was investigated during induction of different emotional states in 27 subjects. Baroreceptors were stimulated through the PRES (Phase Related External Suction) technique, while emotions were induced by means of pleasant, neutral and unpleasant slides. The dependent variables were pain ratings, somatic evoked potentials (N150 and P260) recorded from Fz, Cz and Pz, and skin conductance response (SCR), while heart rate was recorded as a PRES requirement. Valence and arousal ratings were obtained in front of each slide. During suction (external baroreceptor activation) reduced pain ratings, cortical disfacilitation (from Pz, as revealed by N150) and lower SCR were found as compared to pressure (baroreceptor deactivation). Moreover, brain evoked potentials (N150 and P260) reflecting cortical inhibition were found under condition of baroreceptor stimulation during unpleasant slides, but not during pleasant or neutral ones: this result was found in the high blood pressure subjects only. Data showed also a valence effect on pain ratings: pain was evaluated to be higher during unpleasant slides, than neutral and pleasant ones. Results are discussed in the light of "baroreceptor reward" hypothesis, which proposes a learning mechanism for the development of essential hypertension. PMID- 7790292 TI - Migrating microchip. PMID- 7790293 TI - More information on San Clemente goats. PMID- 7790295 TI - Protecting food animal practitioners from public tirades or lawsuits. PMID- 7790294 TI - Comparison of surgical skills of veterinary students trained using models or live animals. PMID- 7790297 TI - Imaging techniques for facilitating diagnosis of hyperadrenocorticism in dogs and cats. PMID- 7790296 TI - The human side of veterinary medicine. Organize or agonize. PMID- 7790298 TI - Livestock producers' expenditures on animal health products and services in 1993. PMID- 7790299 TI - Animal behavior case of the month. The owners observed tail chasing and left hind lameness in their dog. PMID- 7790300 TI - What is your diagnosis? Severe osteochondritis dissecans of the lateral trochlear ridges in a dog. PMID- 7790301 TI - Compendium of chlamydiosis (psittacosis) control, 1995. PMID- 7790303 TI - Hepatozoon canis infection in two dogs. AB - Infection of 60 to 90% of neutrophils with the protozoa, Hepatozoon canis, was detected in 2 dogs. Clinical signs included lethargy, anorexia, and weight loss. Both dogs had severe anemia, leukocytosis, and thrombocytopenia as well as hypoalbuminemia, hyperglobulinemia, and high activities of serum alkaline phosphatase and creatine kinase. Both dogs were treated with imidocarb dipropionate and doxycycline. One dog recovered clinically, with disappearance of parasites from WBC. The other dog died, despite treatment. Necropsy revealed widespread dispersion of schizonts in the parenchymal tissues, but no involvement of skeletal muscle tissues. The disease syndrome that has been identified in the Texas Gulf region is characterized by gait abnormalities associated with multifocal pyogranulomatous myositis, thus, it is distinct clinicopathologically from the syndrome observed in these 2 dogs. PMID- 7790302 TI - Evaluation of three fixation techniques for repair of mandibular fractures in dogs. AB - Bilateral midbody hemimandibular osteotomies were performed between premolars 3 and 4 in 18 adult dogs. Hemimandibles were repaired by use of monocortically applied bone plates (n = 6), an interdental fixator composed of an Erich arch bar and acrylic (n = 6), or a type I external skeletal fixator (n = 6). At the immediate postoperative evaluation, hemimandibles stabilized with interdental fixators had an osteotomy gap distance (mean +/- SEM, 1.6 +/- 0.2 mm) that was significantly (P < 0.05) greater than for hemimandibles stabilized with external skeletal fixators (1.2 +/- 0.3 mm). Osteotomy gap distance of hemimandibles stabilized with external skeletal fixators (1.5 +/- 0.2 mm) was significantly (P < 0.05) greater at weeks 4 (1.1 +/- 0.2 mm) and 8 (0.8 +/- 0.3 mm) after surgery than the osteotomy gap distance of hemimandibles stabilized by application of bone plates. By week 16, significant differences in osteotomy gap distance were not detected between groups. Immediately after surgery, mandibular alignment measurements were not significantly different for dogs with bone plates (0.3 +/- 0.1 mm), interdental fixators (0.3 +/- 0.1 mm), and external skeletal fixators (0.9 +/- 0.5 mm). Mandibular alignment scores were not significantly different between treatment groups during the remaining postoperative period. Occlusal measurements were not significantly different between evaluations performed before surgery and 16 weeks after surgery, regardless of treatment group. Radiographic evidence of healing in hemimandibles stabilized with external skeletal fixators was significantly (P < 0.05) less at 4 and 8 weeks, compared with hemimandibles stabilized with bone plates and interdental fixators; however, radiographic evidence of bone healing was not significantly different between fixation groups at 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790304 TI - Hemophilia B (factor IX deficiency) in a family of German shepherd dogs. AB - Three male German Shepherd Dog pups were treated for vaccination-induced hematomas. Coagulation tests in 2 of these pups revealed markedly prolonged activated partial thromboplastin times, whereas specific coagulation factor tests revealed severe deficiency of factor IX activity. Investigation of the pedigree supported a sex-linked pattern of inheritance and a distant relationship to a pup found to have hemophilia B 7 years earlier. Dogs in the pedigree had variable manifestations of bleeding, including hematomas, deep muscle bleeding, profuse bloody diarrhea, and sudden neonatal deaths. von Willebrand's disease was concurrently detected in several dogs in the pedigree, and may have contributed to the bleeding tendency in some dogs. Medical management of 2 of the 3 pups included transfusion of fresh whole blood, canine fresh-frozen plasma, and canine plasma cryosupernatant, as indicated, and cage rest. Two pups were euthanatized because of the severity of recurrent bleeding episodes. A third dog remains alive, but requires periodic infusions of blood product to maintain hemostasis. PMID- 7790305 TI - Use of pharmacologically induced ejaculation to obtain semen from a stallion with a fractured radius. AB - Ejaculation was pharmacologically induced in a 13-year-old Quarter Horse stallion with a spiral fracture of the radius. The owners desired to have semen from the stallion frozen prior to euthanatizing the horse, but because of the debilitating injury, standard methods of semen collection could not be used. With the stallion standing quietly in a stall, a plastic collection bag was positioned over the stallion's penis, and clomipramine hydrochloride (2.2 mg/kg of body weight, IV) was administered. Fifty-five minutes later, xylazine hydrochloride (0.5 mg/kg, IV) was administered. The stallion ejaculated 2 minutes after xylazine administration. The semen sample was of low volume and had a high concentration of spermatozoa; however, motility of spermatazoa was poor and the semen was unacceptable for freezing. The stallion was euthanatized. Semen aspirated from the epididymis after euthanasia was of similar quality to that of the ejaculated sample. Pharmacologic induction of ejaculation can be useful for obtaining semen from stallions when standard techniques cannot be applied. PMID- 7790306 TI - Sternothyrohyoideus myectomy or staphylectomy for treatment of intermittent dorsal displacement of the soft palate in racehorses: 209 cases (1986-1991). AB - The efficacy of sternothyrohyoideus myectomy (SM) and staphylectomy as treatments for intermittent dorsal displacement of the soft palate was evaluated in 209 racehorses (126 Thoroughbreds, 83 Standardbreds). The 2 most common complaints were respiratory tract noise (75% of horses) and exercise intolerance (51% of horses). Stopping, defined as the inability to finish the race at racing speed, was reported in 40% of the horses. Endoscopy at rest revealed evidence of abnormal epiglottic anatomy (hypoplasia or flaccidity) in 51% of the horses and abnormal soft palate function in 36% of the horses. Race records were available for 149 (77 Thoroughbreds, 72 Standardbreds) horses. The sex distribution consisted of 38% sexually intact males, 20% geldings, and 42% females, with a mean age of 3.4 years. Sixty-nine horses underwent staphylectomy, with a mean of 16 weeks to first stage after surgery. Eighty horses underwent SM, with a mean of 10 weeks to first start. Sternothyrohyoideus myectomy was performed on significantly more (P < 0.05). Thoroughbreds than Standardbreds, and staphylectomy was performed on significantly (P < 0.0001; chi 2 = 39.56) more Standardbreds than Thoroughbreds. After surgery, most horses (74%) had no change in class; however, more moved up in class (17%) than down (9%). On the basis of comparison of earnings for 3 starts before surgery with that for 3 starts after surgery, successful outcome was obtained in 60% of the horses (35 Thoroughbreds, 13 Standardbreds) that received SM and in 59% of the horses (11 Thoroughbreds, 30 Standardbreds) that received a staphylectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790307 TI - Alar fold resection in horses: 24 cases (1979-1992). AB - Between 1979 and 1992, the alar folds were resected bilaterally in 22 horses and unilaterally in 2 horses. Abnormal respiratory tract noise and exercise intolerance were the primary complaints prior to surgery. Significantly (P = 0.01) more Standardbreds underwent resection of the alar folds, compared with the number of Standardbreds in the hospital population during the same period. The alar folds palpated abnormally thick in 13 horses and normal in 11 horses. Temporary dilatation of the nares with mattress sutures or clips lessened the respiratory tract noise and improved exercise tolerance in all 8 horses in which the diagnostic test was performed. Manual elevation of the alar folds reduced respiratory noise in the 11 horses evaluated. Long-term follow-up evaluation by telephone was available for 14 horses. All surgical incisions had healed cosmetically. Respiratory tract noise was decreased, and exercise tolerance improved in 10 of 14 (71%) horses. Complete charted racing information was obtained for 16 horses. Fourteen horses started their first race a mean of 118 days (range, 13 to 321 days) after surgery. The mean number of starts after surgery was 51, with 14 of 16 (88%) horses starting more than 6 times after surgery. Of the 16 horses, 8 horses raced at least 3 times before and after surgery; 4 had improved racing performance, 2 had similar performance, and 2 had decreased performance. Five Standardbreds never raced, and 1 Standardbred raced once before surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790308 TI - Management of a radial fracture in an adult bull. AB - An 823-kg 4-year-old Holstein bull was examined because of acute lameness of the left forelimb. Radiography revealed a closed, comminuted, spiral fracture of the radius that extended from the distal portion of the diaphysis to the antebrachiocarpal joint. The fracture was repaired with combination of internal fixation (2 compression plates, 1 of which incorporated a condylar screw and both of which were luted) and external coaptation (full-limb cast and Thomas-Schroeder splint). The development of larger implants and the combination of internal and external fixation methods provides hope that certain fractures in cattle that were once thought irreparable can now be treated. PMID- 7790309 TI - Hydrops uteri in a caprine doe pregnant with goat-sheep hybrid fetuses. AB - A 5-year-old caprine doe was examined for abdominal enlargement and inability to stand. Hydrops uteri was diagnosed via ultrasonography, and was determined to be the cause of hind limb paresis. The placentomes appeared to be abnormal in shape and number. Uterine fluid electrolyte concentrations were similar to fluid from cows and sheep with hydrops amnion. Two fetuses were dead at the time of induced parturition. Hydrops uteri is rare in goats and, in the goat of this report, was believed to be caused by pregnancy with an unusual goat-sheep hybrid. The placental abnormalities discovered by ultrasonography may have been responsible for the abnormal accumulation of fluid, but a fetal abnormality also was considered to be possible. PMID- 7790310 TI - Use of facilitated ankylosis in the treatment of septic arthritis of the distal interphalangeal joint in cattle: 12 cases (1987-1992). AB - Medical records were reviewed for 12 cattle with septic arthritis of the distal interphalangeal joint that were treated by use of facilitated ankylosis. Information on signalment, clinical signs, digit affected, radiographic findings, and type and duration of treatment were compiled. Owners were contacted for information about the convalescent period, reasons for culling, productivity, and outcome. Outcome was classified as successful or unsuccessful on the basis of lameness, growth pattern, and whether the cattle were subsequently productive. Cause of the septic arthritis was unknown in 9 of 12 (75%) cattle. Eleven of 12 (92%) cattle represented beef breeds. Cattle were lame for a mean of 5.3 weeks before admission. In 8 of 12 (67%) cattle, a trephine was used in the creation of an arthrostomy, the middle and distal phalanges were curetted, and the joint was lavaged with isotonic solution. A drill bit was used in 4 of 12 (33%) cattle to remove articular cartilage and facilitate ankylosis. Convalescent period after discharge from the hospital was 1 to 7 months (mean, 4 months; median, 4 months). After that period, all cattle had an apparently normal gait. Eight of 12 (67%) cattle were maintained in their herd of origin. None of the cattle were culled because of lameness. Two of 12 (17%) cattle had a deformation of the affected digit. According to the criteria for successful outcome that were used in the study reported here, the success rate was 100%. Treatment of septic arthritis of the distal interphalangeal joint by use of facilitated ankylosis is an alternative to digit amputation and is recommended to promote longevity and productivity. PMID- 7790311 TI - Bartonellosis. PMID- 7790312 TI - Xenogenization. PMID- 7790313 TI - Nuclear accumulation of p53 in normal human fibroblasts is induced by various cellular stresses which evoke the heat shock response, independently of the cell cycle. AB - Nuclear accumulation of p53 is induced by various DNA damaging agents (the p53 response). Induction of nuclear accumulation of p53 after various cellular stresses, mostly other than DNA damage, including heat shock, was examined in normal human fibroblasts by immunostaining and flow cytometry using a mouse anti p53 monoclonal antibody. Immunostaining revealed nuclear accumulation of p53 within 6 h after various stresses [heat shock, osmotic shock, heavy metal (Cd), blockers of the cellular respiratory system (NaN3), amino acid analogues (azetidine and canavanine), an inhibitor of protein synthesis (puromycin), and oxygen free radicals (H2O2)]. Heat shock proved to be one of the most effective inducers among these stresses. FACScan analysis revealed that this induction of p53 occurred regardless of the stage in the cell cycle and that accumulation of cells in G2/M occurred. As all of these stresses are known to induce the heat shock response, the mechanism of p53 induction after stresses and that of heat shock response may share, at least partly, some common signaling pathway(s). PMID- 7790314 TI - A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue. AB - We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis. PMID- 7790315 TI - High-energy underwater shock wave treatment for internal iliac muscle metastasis of prostatic cancer: a first clinical trial. AB - The first clinical trial of high-energy shock wave (SW) combined with chemotherapy to treat metastasis of prostate cancer in the internal iliac muscle was conducted. The patient, a 57-year-old man, diagnosed as having mucin producing, poorly differentiated adenocarcinoma of the prostate invading the bladder wall, had been treated by total cystoprostatectomy. Five months later, metastatic tumors were found in the left axillar subcutaneous tissue and the right internal iliac muscles. For the axillar metastasis we performed radiation and left subclavicular arterial infusion of cisplatin 70 mg, THP-adriamycin (THP) 50 mg and methotrexate 50 mg. For the right internal muscular metastasis, 10,000 to 20,000 shots of SW and simultaneous intravenous injection of carboplatin 100 mg and THP 10 mg were carried out. Neither of the tumors decreased in size, but on magnetic resonance images, the SW-treated tumor exhibited a central low intensity area. The SW-treated tumor was resected and central necrosis and a collection of mucin in the central area were observed. Hormone-resistant prostate cancer is well-known to be a multidrug-resistant tumor. It is noteworthy that SW and chemotherapy induced necrosis in such a refractory cancer without any significant side effects. PMID- 7790317 TI - Increased susceptibility to N-nitrosomethylurea gastric carcinogenesis in transforming growth factor alpha transgenic mice with gastric hyperplasia. AB - Glandular stomach carcinogenesis after N-nitrosomethylurea (NMU) treatment was examined in transgenic mice bearing a human transforming growth factor alpha (TGF alpha) cDNA driven by the mouse metallothionein-I promoter (mouse line MT100) in the inbred mouse line FVB/N. Untreated MT100 mice exhibit a severe age-related gastric fundic hyperplasia. Both sexes of MT100 mice were given 10 weekly intragastric intubations of 0.5 mg NMU per mouse from 6 weeks of age and/or zinc chloride in drinking water to stimulate transgene expression from 5.5 weeks of age to the experiment termination. Animals were killed sequentially at 10, 19 and 29 experimental weeks. Several histochemical markers (AB-PAS, TGF-alpha, pepsinogen isozyme 1, proliferating cell nuclear antigen) were used. Abnormal histochemical patterns were found in untreated MT100 and NMU-treated MT100 mice for all 4 markers of differentiation and carcinogenesis. Precancerous lesions including atypical and/or adenomatous hyperplasia were found in the fundic region of 16/22 male and 8/22 female MT100 mice but not in 27 male and 24 female FVB/N mice treated with NMU. One of 22 MT100 males had fundic carcinoma. FVB/N mice treated with NMU had neither precancerous lesions nor carcinomas in the fundus. Well differentiated adenocarcinomas in the pyloric region were induced at incidences of 2/22 male and 1/22 female MT100 mice treated with NMU and 4/27 male and 4/24 female FVB/N mice treated with NMU. Both strains also had a high incidence (55 to 92%) of squamous cell carcinomas of the forestomach. In conclusion, TGF-alpha induced a hyperplastic lesion in the gastric fundus that appeared to predispose the MT100 mice to carcinogenesis by NMU. PMID- 7790316 TI - Intraluminal epidermal growth factor affects growth of N-methyl-N-nitrosourea initiated rat bladder carcinoma. AB - To confirm our recent finding that epidermal growth factor (EGF) appeared to contribute to the tumor-enhancing effect demonstrated by normal rat urine, we conducted 2 experiments using our heterotopically transplanted rat urinary bladder model. In experiment 1, after a single dose (0.25 mg) of N-methyl-N nitrosourea (MNU), we intravesically administered EGF (0.05 ml of 500 ng/ml phosphate-buffered saline) once a week for 30 weeks. Instillation of EGF induced a significantly larger number of tumors than did instillation of the vehicle (P = 0.03). EGF without MNU initiation did not induce tumors. In experiment 2, 2 groups received instillation of killed Escherichia coli (5 x 10(8) cells)/0.5 ml phosphate-buffered saline once a week for 4 weeks to expand the MNU-initiated cell population. Subsequent EGF treatment significantly increased the incidence of tumors (P = 0.01). In the groups which did not receive killed E. coli, EGF treatment induced a significantly higher number of tumors than did vehicle treatment (P < 0.001). All of the tumors were low-grade, superficial transitional cell carcinomas. These observations indicate that EGF acts as a growth stimulating factor on dormant neoplastic cells and thereby increases the number of tumors. PMID- 7790318 TI - Subchromosomal mapping of a putative transformation suppressor gene on human chromosome 1. AB - We previously reported that the introduction of a normal human chromosome 1 via microcell-mediated chromosome transfer suppressed the transformed phenotypes, including anchorage-independent growth, of Kirsten murine sarcoma virus transformed NIH3T3 (DT) cells. Soft-agar clones derived from DT-#1 cells (DT cells with an intact transferred human chromosome 1) exclusively failed to retain an intact form of this chromosome. Thus, a gene(s) with a suppressive activity on this chromosome had probably been lost. We therefore attempted to identify a commonly deleted region on human chromosome 1 in these soft-agar clones. Although eight of the 9 soft-agar clones examined still contained regions on this chromosome, to a greater or lesser degree, four loci on 1q21 and 1q23-q24 were commonly lost in all of them. Furthermore, the soft-agar clones had growth properties similar to those of DT cells. Thus, chromosome and DNA analyses suggested that human 1q21 and/or 1q23-q24 carries a transformation suppressor gene(s) which controls the transformed phenotypes of DT cells. PMID- 7790319 TI - Establishment and characterization of non-small cell lung cancer cell lines resistant to mitomycin C under aerobic conditions. AB - To elucidate the mechanisms of acquired resistance to mitomycin C (MMC) in non small cell lung cancer (NSCLC), we established two MMC-resistant NSCLC sublines by continuous exposure to MMC, using PC-9 as a parent cell line. The sublines, PC 9/MC2 and PC-9/MC4, were 6.4- and 10-fold more resistant to MMC than their parent cell line, respectively, at the IC50 value as determined by MTT assay. They exhibited cross-resistance to EO9, but were not resistant to cisplatin, vindesine, etoposide, carboquone, or KW-2149, a novel MMC derivative. They were collaterally sensitive to adriamycin and menadione. Accumulation of the drug was decreased in the resistant sublines to about 60% of that in the parent cells. Cytosolic DT-diaphorase (DTD) activities were decreased to 13.5 +/- 3.2 in PC9/MC2 and 1.3 +/- 0.6 in PC-9/MC4 from 261.5 +/- 92.7 nmol/min/mg protein in the parent PC-9. NADH:cytochrome b5 reductase activities in both of the resistant cell lines were significantly decreased as compared to that in the parent cell line. Addition of dicumarol resulted in a two-fold increase in IC50 value in PC 9, whereas the IC50 value showed no change in PC-9/MC4. Moreover, dicumarol did not affect the sensitivities to KW-2149 but decreased the sensitivities to EO9 in both the parent and the resistant cell lines. Formation of an alkylating metabolite was significantly decreased in the resistant cells, in parallel to the degree of resistance. We concluded that deficient drug activation due to decreased DTD activity was important as a mechanism of resistance to MMC in PC-9, a relatively DTD-rich NSCLC cell line. PMID- 7790321 TI - Synergistic effect of methionine-depleting total parenteral nutrition with 5 fluorouracil on human gastric cancer: a randomized, prospective clinical trial. AB - Methionine-depleting total parenteral nutrition (Met-depleting TPN), infusing AO 90 amino acid solution (lacking both L-methionine and L-cysteine) as a sole nitrogen source, showed synergistic effects with 5-fluorouracil (5-FU) in tumor bearing rats and in clinical trials with gastrointestinal tract cancers. In this study, the effect of Met-depleting TPN with 5-FU upon thymidylate synthase (TS) activity was examined, and the histological effect of this treatment on human gastric cancer was evaluated. Fourteen preoperative advanced gastric cancer patients were divided randomly into two groups. Seven cases were given Met depleting TPN for 7 days before surgery with continuous intravenous administration of 5-FU (500 mg/body per day; total 4.0 g/body) (AO-90 group). The other 7 received conventional L-methionine-containing TPN with 5-FU (control group). All patients underwent gastrectomy without complications due to these treatments. Resected materials were examined for TS kinetics, and the anti-cancer effect was also assessed histopathologically. The specimens in the AO-90 group showed marked degeneration of cancer, while almost no effect was seen in the control group. The free TS activity of carcinoma tissue in the AO-90 group was decreased and the TS inhibition rate was increased in comparison with the control group (P = 0.0165 and P = 0.0243, respectively). Met-depleting TPN appears to play a role as a biomodulator of 5-FU in human gastric cancer. PMID- 7790322 TI - Phase I study and clinical pharmacological evaluation of daily oral etoposide combined with carboplatin in patients with lung cancer. AB - Twenty-eight patients with inoperable or relapsed lung cancer were given a combination of oral etoposide, administered once a day at doses ranging from 40 to 60 mg/m2/day (d) for 21 consecutive days, and carboplatin, administered intravenously over 1 h at doses ranging from 300 to 400 mg/m2 on day 1 to determine the appropriate doses of this combination. In addition, pharmacokinetic and pharmacodynamic analyses were performed. All the patients had a performance status of 0 to 1. Serum etoposide and free platinum (Pt) concentrations were measured using high-performance liquid chromatography and atomic absorption, respectively. Myelosuppression, nausea and vomiting were the dose-limiting toxicities of this schedule. The maximum tolerated dose (MTD) was 50 mg/m2/d oral etoposide for 21 days and 400 mg/m2 i.v. carboplatin on day 1. For heavily pretreated patients, the MTD was 40 mg/m2/d oral etoposide for 21 days and 350 mg/m2 i.v. carboplatin on day 1. No cumulative increase in the area under the concentration-time curve (AUC) for oral etoposide over time was observed. There were significant correlations between the free Pt serum level (6, 8, 12, 24 h post-dose) and etoposide AUC level (days 1, 10 and 21) for graded hematological toxicity, and the percentage decreases and nadir counts of hemoglobin, leukocytes, neutrophils and platelets. Several pharmacodynamic models were developed to predict the hematological toxicity. In order to facilitate pharmacodynamic evaluations in future studies, a limited sampling model for oral etoposide was also developed and validated. PMID- 7790320 TI - Functional and T cell receptor gene usage analysis of cytotoxic T lymphocytes in fresh tumor-infiltrating lymphocytes from human head and neck cancer. AB - Twenty-one cytotoxic T lymphocyte (CTL) clones or lines that killed autologous tumor cells, but not allogeneic tumor, K562, or Daudi cells, were established from fresh tumor-infiltrating lymphocytes of two individuals (HP-1 and HP-2) with head and neck cancer by limiting dilution in the presence of recombinant interleukin-2. Sixteen (76%) of these 21 clones or lines comprised CD4+ CTLs and the other five comprised CD8+ CTLs. These observations suggest that autologous tumor cell-specific CD4+ CD8- and CD4- CD8+ CTLs are present in vivo at the tumor site in head and neck cancer. Analysis of T cell receptor (TCR) gene arrangements in 20 of the 21 CTL isolates with reverse transcriptase and the polymerase chain reaction revealed that five of 12 and five of eight isolates from HP-1 and HP-2, respectively, were clones, the other isolates being lines comprised of two or more clones. Each CTL clone showed a different combination of V alpha and V beta gene expression, suggesting that more than five different tumor-associated antigens may be expressed on head and neck cancer cells. In spite of the diversity of TCR alpha beta combinations, TCR V alpha 1, V alpha 3, V alpha 8, V alpha 10, V beta 8, V beta 9, and V beta 17 were also frequently expressed in both patients. These data suggest that specific CTLs proliferate oligoclonally and contribute to the specific immune response against head and neck cancer in vivo. PMID- 7790324 TI - A case of focal cancer of the rectum without microsatellite instability: the personal experience of a basic researcher. PMID- 7790323 TI - Comparison of false negative rates among breast cancer screening modalities with or without mammography: Miyagi trial. AB - False negative rates were compared in two screening modalities, physical examination with or without mammography, in an intervention study for women aged over 50 in Miyagi Prefecture. Thirty-five breast cancers were detected in 12,515 subjects who participated in the trial consisting of physical examination and mammography, whereas 44 breast cancers were detected in 50,105 subjects who received physical examination alone, so that the detection rates were 0.28% and 0.09%, respectively. Among 50,061 subjects who received physical examination alone, 8 women were diagnosed as having breast cancer within 12 months after the screening, while only one of 12,480 screenees receiving the combined modality was so diagnosed, implying false negative rates of 15.4% and 2.8%, respectively. When the screening sensitivity in the combined system was analyzed according to each single modality, the false negative rate provided by physical examination with mammography turned out to be 2.8%, significantly lower than that (33.3%) by the physical examination alone. Minimal breast cancers represented 25.7% of all screen-detected cancers in the combined modality, compared with 9.1% in the modality without mammography. The trial thus indicates that physical examination combined with mammography may be an appropriate modality for breast cancer screening in women aged over 50 on the basis of screening sensitivity. PMID- 7790325 TI - The chest x-ray in mitral stenosis. PMID- 7790326 TI - Radiological case of the month. Salter III fracture of distal right tibia. PMID- 7790328 TI - Wrapped autologous greater saphenous vein bypass for severe limb ischemia in patients with varicose veins. Preliminary report. AB - The greater saphenous veins in patients with varicose veins has been overlooked as a conduit for arterial bypass. Greater saphenous veins is often normal and when only parts of the greater saphenous veins are of normal size, a veno-venous or a graft composite bypass may be performed. The goal of this preliminary study was to asses if wrapped autologous greater saphenous veins could be suitable conduits for arterial bypass in patients presenting with critical ischemia. In three patients the greater saphenous veins had one to four dilatations which were wrapped with short segments of Polytetrafluoroethylene graft. In three other patients, the dilated area being longer, the greater saphenous veins were totally wrapped in a hand-made mesh of Dacron. No complications were due to the wrapping procedure and the unwrapped segments did not dilate during a mean three year follow-up. We conclude that wrapped autologous greater saphenous veins may help save limbs of patients with critical ischemia. As an underestimated proportion of patients presenting with varicose tributaries have normal or quite normal greater saphenous veins, the caliber of the greater saphenous veins should be carefully measured before treating the varicose veins. All greater saphenous veins suitable for an arterial bypass should be preserved remembering that one or several dilatations may be wrapped if the greater saphenous veins is used as an arterial substitute. Patients should be informed of the reasons for this choice. PMID- 7790327 TI - Role of A-V shunting in varicose veins: therapeutic implications. PMID- 7790329 TI - Physico-chemical observations on a failed Greenfield vena cava filter. AB - A Greenfield vena cava filter for the prevention of thromboembolism failed in vivo due to the displacement of 2 of the 6 legs and their subsequent break. The explanted stainless steel filter was analyzed with an electron microscope and energy dispersion system in order to assess the reason for the break. Fatigue and corrosion of the metal were responsible for the failure. PMID- 7790330 TI - In vitro testing of six inferior vena cava filters: filtering efficiency and pressure measurements. AB - The purpose of this study is to compare in standarddised ex vivo conditions the performances of six percutaneous vena cava filters available on the European Market. METHODS: We use a mock circulation with polyethylene beads simulating clots to objectively determine the filtering efficiency of the different devices. We measured pressure at contact points with the wall of the tube simulating vena cava, and also gradient of pressure induced by the empty and full filter. Statistical analysis of the data obtained (at least 100 measurements for each filter) showed great consistency in the response of a given filter to the different conditions of mock circulation. RESULTS: The Greenfield Filter, which served as the reference, was compared to the other models. Its filtering efficiency was acceptable as was that of the L.G. Filter. The Cardial Filter and Vascor Filter were the most efficient. The Antheor Filter and the Filcard Filter performed poorly. CONCLUSION: The mock circulation give reliable and reproducible data on the filtering efficiency for a device but ease of placement and clinical studies must be taken into account for the choice of the filter. PMID- 7790333 TI - Efficacy and limitation of a left ventricular assist system in a patient with dilated cardiomyopathy accompanying multi-organ dysfunction. AB - A left ventricular assist system (LVAS, Toyobo CO., LTD., Japan) was used to provide life support for 190 days in a 44-year-old male patient with end-stage dilated cardiomyopathy. Before LVAS implantation, heart failure and cardiogenic shock with multi-organ dysfunction progressed despite the use of intra-aortic balloon pumping (18 days), mechanical ventilatory support (15 days), continuous veno-venous hemofiltration (two days) and intravenous administration of catecholamines. Before LVAS implantation, the patient had marked hepatic and renal dysfunction (total bilirubin 6.1, BUN 73 and serum creatinine 3.1 mg/dl). Those functions returned to normal (total bilirubin 1.2, BUN 11 and serum creatinine 0.6 mg/dl) one month after implantation. He was complicated by multiple cerebral embolisms occurring on the 9th, 57th and 175th postoperative days and died 190 days after surgery. Autopsy showed thrombi attaching to the diaphragm of the blood pump and multiple embolisms in the kidney and the spleen. By scanning electron microscopic examination, initial thrombi with attached erythrocytes were seen on the diaphragm surface without intimal lining formation. In conclusion, LVAS support can be useful for patients with end-stage heart disease complicated by multi-organ dysfunction. However, the LVAS may cause thromboembolic complications over the prolonged use. PMID- 7790331 TI - A new ePTFE stretch graft for aorto-iliac reconstructions. Surgical evaluation and one year follow-up with magnetic resonance imaging. AB - Since its introduction at the beginning of the 60s Dacron has proved to be a reliable and durable substitute for aortic reconstructions. It is however susceptible to late thrombosis, infection and aneurysmal dilatation in a significant number of cases. ePTFE vascular prosthesis, introduced in 1972, have proved to perform well for peripheral reconstructions and was used in aortoiliac position since 1980. In 1991 a new type of ePTFE rendered longitudinally extensible (Gore-Tex Stretch) was introduced into clinical practice. The aim of this study is to evaluate surgical performance, short term patency and interaction with periprosthetic tissues of Gore-Tex Stretch straight and bifurcated prosthesis. Between October 1991 and December 1993, 59 patients underwent aortic reconstruction at our Institution either for infrarenal aortic aneurysm (19 patients, 16 males, 3 females, mean age 68.8 +/- 8.5 years) or for aortoiliac occlusive disease (40 patients, 36 males, 4 females, mean age 60.5 +/- 7.2 years). Forty-eight bifurcated and eleven straight grafts were implanted using Gore-Tex sutures. Preoperative workup included Ultrasonography, Magnetic Resonance Imaging (MRI) in patients with aneurysms and Intra Arterial Digital Subtraction Arteriography (DSA) in patients with occlusive disease. Intraoperative parameters were recorded. Postoperative follow-up included ultrasonographic evaluation at 1st and 7th day, 15th postoperative week and at 3 monthly intervals; Intra Venous DSA before dismission and MRI at the 1st and 15th postoperative week. Intraoperatively the grafts proved to be soft and flexible with good handling and suturing characteristics. Perioperative bleeding was 480 +/- 299 ml for occlusive disease cases and 633 +/- 314 for aneurysm cases. No operative mortality was recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790332 TI - Non-infective high fever after replacement of thoracic aorta using collagen impregnated Dacron prosthesis. AB - We present three patients who were complained of a high fever without infective signs clinically and bacteriologically after the implantation of a woven Dacron prosthesis impregnated with collagen for thoracic aortic aneurysm. High fever appeared on the third on fourth day after surgery, and continued for three to seven days. The maximum fever ranged 39.1 to 39.9 degrees C. There was a close relationship between the value of C-reactive protein and the duration of a high fever. There were no differences between patients with and without a high fever in white blood cell counts, and other hematological and biochemical examinations. Non-infective high fever may be encountered in the postoperative acute phase following the implantation of a Hemashield prosthesis. PMID- 7790334 TI - Perioperative coronary artery spasm in modified Bentall's operation for annulo aortic ectasia in Marfan's syndrome. A case report of perioperative chordal rupture of the mitral valve. AB - We experienced a rare case of Marfan's syndrome with annulo-aortic ectasia, aortic regurgitation and Prinzmetal's variant angina. In a modified Bentall's operation (button technique), perioperative severe coronary artery spasm occurred in spite of the preventive use of nitroglycerin infusion, which resulted in profound ventricular fibrillation and subsequent chordal rupture of the mitral valve with Sellers IV regurgitation. Use of nicardipine contained in cardioplegia, continuous infusion of nicardipine and nitroglycerin after aortic declamping completely prevented coronary spasm throughout the course of a second surgery for mitral valve replacement. It is worthy to report this case because of rarities such as Marfan's syndrome accompanied by Prinzmetal's variant angina, perioperative coronary artery spasm in modified Bentall's operation, and perioperative chordal rupture of the mitral valve and progression of mitral valve regurgitation. We also stress the efficacy of a new calcium antagonist, nicardipine, to prevent coronary artery spasm during open heart surgery. PMID- 7790335 TI - Use of thoracoscopy and a minimal thoracotomy, in mammary-coronary bypass to left anterior descending artery, without extracorporeal circulation. Experience in 2 cases. AB - A new surgical approach to mammary-coronary bypasses, to the left anterior descending artery, without the use of extracorporeal circulation, is described here. A minimal left anterior thoracotomy and the use of thoracoscopy are combined in this procedure performed in two patients (54-year-old male and 56 year-old male). Results were excellent: both patients were soon discharged from hospital (3 days patient 1 and 36 hours patient 2). Neither blood nor inotropic drugs were required. New angiographies previous to discharge were done, showing 100% patency of the mammary grafts. Both patients are angina-free. Due to its simplicity, and with more experience, this technique could be a good alternative for patients with severe lesions of the left anterior descending artery. PMID- 7790336 TI - Ischemic papillary muscle dysfunction in an adult with a parachute mitral valve. AB - A case of severe mitral regurgitation secondary to an infarct of a single papillary muscle in a 65-year-old female with a parachute mitral valve is described. To the best of our knowledge this is the oldest patient reported with this rare congenital anomaly. The clinical and echocardiographic features are discussed. PMID- 7790337 TI - A rare complication of mitral valve replacement: sudden cardiac death for immobilization of disc valve by an unraveled suture. AB - Disc immobilization caused by an unraveled suture in a mitral valve prosthesis represents a rare extrinsic complication in heart valve replacement. We report a case of a 54-year-old white male who underwent mitral valve replacement because of a severe mitral regurgitation. A Bjork-Shiley tilting disc was implanted with interrupted "U" shaped 3/0 silk sutures. There were no complications and the patient was discharged in the 10th postoperative day. Twenty days after surgery the patient died for acute pulmonary edema. Autopsy revealed an unraveled suture producing interference with the tilting disc as a cause of disc prosthesis immobilization in closed position. The possible explication of this rare complication is the combination between unraveled suture and the pleating held by Teflon sewing ring after restoring heart function. A flaccid heart can produce an overestimation of the annulus size and the valve ring can bring an anomalous interference with the valve mechanism. In conclusion disc immobilization by an unraveled suture is a complication that can occur very rarely but an accurate prevention must be warrant particularly with a tilting disc more than a beleaflet prosthesis. PMID- 7790338 TI - Surgical repair of a ventricular septal defect in a patient with trisomy 8 syndrome. AB - We surgically repaired a ventricular septal defect (-VSD) in a patient with trisomy 8 syndrome. This case illustrated a number of characteristic clinical features associated with trisomy 8 syndrome patients which have previously been reported in the literature. However, our patient's VSD was not found to be particularly different from the VSD of patients without chromosomal abnormalities during either the surgery or the postoperative course. PMID- 7790340 TI - Paraplegia as a result of intra-aortic balloon counterpulsation. AB - A case of paraplegia after a perioperative intra-aortic balloon support is presented. This rare and devastating complication is the twelfth reported in international literature. PMID- 7790341 TI - Closure of leaks by fibrin gluing. Effects of various application techniques and temperatures. AB - This study was performed to determine the differences in covering power obtained with fibrin gluing using three different methods, layered, mixing, and spraying. The experimental system consisted of a 2 x 2 cm plastic plate with a hole 1 mm in diameter, a plastic syringe, and a digital manometer. The internal pressure of the syringe barrel was measured with the digital manometer. Five minutes after fibrin glue membranes (1 mm in thickness) had been prepared on the plastic plate with the layered, mixing, or spray method, the plunger of the syringe was pushed slowly, and the maximum internal pressure in the syringe barrel was measured, just before the breakage of the membrane. Experiments were performed five times at each four temperatures, 12 degrees C, 17 degrees C, 22 degrees C and 37 degrees C. Covering power of fibrin glue membranes (units: mmHg; atmospheric pressure 760 mmHg) were as follows: 1) Layered method (12 degrees C: 810.0 +/- 68.6, 17 degrees C: 769.0 +/- 10.2, 22 degrees C: 812.0 +/- 112.4, 37 degrees C: 773.6 +/- 24.4). 2) Mixing method (12 degrees C: 956.6 +/- 219.3, 17 degrees C: 972.4 +/- 243.5, 22 degrees C: 1045.2 +/- 233.0, 37 degrees C: 1059.0 +/- 220.2). 3) Spray method (12 degrees C: 1010.0 +/- 231.1, 17 degrees C: 1144.4 +/- 170.6, 22 degrees C: 1148.0 +/- 234.7, 37 degrees C: 1250.0 +/- 111.8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790339 TI - Late spontaneous chylopericardium following complex cardiac surgery. AB - Chylopericardium as an isolated complication after open heart surgery is a rare event. We present here a case of late postoperative chylopericardium and comment on the clinical course, the aetiopathology and treatment. PMID- 7790342 TI - Ischemic conditioning of the rat stomach: implications for esophageal replacement with stomach. AB - BACKGROUND: Esophagectomy, with gastric pull up replacement, is not uncommonly complicated by leakage from the esophagogastrostomy anastomosis. Occult ischemia of the mobilized gastric fundus is a major etiologic factor in anastomotic leakage. OBJECTIVE: To test the hypothesis that tissue perfusion in a partially devascularized stomach will improve over time by a process of ischemic conditioning ("delay" phenomenon). EXPERIMENTAL DESIGN COLON: Laboratory study of partial gastric devascularization in rats. ANIMALS: Twenty rats. INTERVENTIONS: Partial gastric devascularization was achieved by ligation of the left gastric artery. MEASURES: Gastric perfusion was measured with a laser-Doppler flowmeter (in tissue perfusion units, TPU). Perfusion measurements were made at baseline, after vessel ligation, at 7 days, and at 14 days. RESULTS: Perfusion immediately after vessel ligation (23.8 +/- 6.0 TPU) was significantly lower than baseline gastric tissue perfusion (88.4 +/- 9.8 TPU) (p < 0.00001). After 7 days, tissue perfusion had increased (54.4 +/- 9.2 TPU), but it was significantly lower than baseline values (p < 0.00005). After 14 days, perfusion was increased (71.7 +/- 8.6 TPU) compared to 7 day measurements (p < 0.001), but it was still significantly lower than baseline gastric tissue perfusion (p < 0.002). Nevertheless, 14 day perfusion was 81% of baseline values. CONCLUSIONS: After partial devascularization, gastric perfusion steadily improves by a process of ischemic conditioning ("delay" phenomenon). The principle of ischemic conditioning may be clinically applicable to the gastric pull up operation. PMID- 7790343 TI - The results of three cases of unilateral pulmonary embolectomy through right thoracotomy approach for chronic pulmonary embolism. AB - Three patients with chronic pulmonary embolism underwent successfully unilateral pulmonary arterial thromboembolectomy. In these cases, severe degree of right heart failure and respiratory distress were the primary indications to the operation. Under normothermic partial cardiopulmonary bypass, right unilateral pulmonary thromboembolectomy were performed with beating heart. Distal counter incision was found to be facilitated to remove thrombi completely from the distal pulmonary artery. In the results of long-term study, postoperative cardiac catheterization data encouraged us to use this technique in the surgical treatment for the selective cases of this disease. All three patients have been doing well without any sign of recurrence up to 17 years of the surgery. PMID- 7790344 TI - Long-term survival in a surgically treated non-encapsulated mediastinal primary liposarcoma. Diagnostic utility of core-needle biopsy for mediastinal tumors. AB - Primary liposarcomas of the mediastinum are uncommon tumors. Only six cases of mediastinal liposarcomas with survival after surgery longer than five years have been reported and only one of these was a non-encapsulated tumor. We report a new case of non-encapsulated primary liposarcoma of the mediastinum with long-term survival. The diagnosis was carried out using a CT-guided core-needle biopsy. We emphasize the utility of this technique to diagnose this kind of mediastinal tumors. A non-encapsulated primary liposarcoma of the mediastinum surgically treated with long-term survival is reported. We emphasize the diagnostic utility of CT-guided core-needle biopsy for the tumors. PMID- 7790345 TI - Adequate de-airing during cardiac surgery. PMID- 7790346 TI - BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication. AB - We have recently cloned and characterized a human member (BM28) of the MCM2-3-5 family of putative relication factors (Todorov, I.T., R. Pepperkok, R.N. Philipova, S. Kearsey, W. Ansorge, and D. Werner. 1994. J. Cell Sci. 107:253 265). While this protein is located in the nucleus throughout interphase, we report here a dramatic alteration in its nuclear binding during the cell cycle. BM28 is retained in the nucleus after Triton X-100 extraction in G1 and early S phase cells, but is progressively lost as S phase proceeds, and little BM28 is retained in detergent-extracted G2 nuclei. BM28 that is resistant to extraction in G1 nuclei is removed by DNase I digestion, suggesting that the protein is chromatin associated. In addition, we present evidence for variations in the electrophoretic mobility of BM28 that may reflect posttranslational modifications of BM28 during the cell cycle. During mitosis, BM28 is present as a fast migrating form, but on entry into G1, the protein is converted into a slow migrating form. With the onset of S phase, the slow-migrating form is progressively converted into the fast form. BM28 is phosphorylated at all stages of the cell cycle, but during interphase the fast form is hyperphosphorylated compared with the slow form. These apparent changes in modification may reflect or effect changes in the nuclear binding of BM28. The behavior of BM28 is not dissimilar to related proteins in Saccharomyces cerevisiae, such as Mcm2p, which are excluded from the nucleus after DNA replication. We speculate that BM28 may be involved in the control that limits eukaryotic DNA replication to one round per cell cycle. PMID- 7790347 TI - Nuclear envelope breakdown is under nuclear not cytoplasmic control in sea urchin zygotes. AB - Nuclear envelope breakdown (NEB) and entry into mitosis are though to be driven by the activation of the p34cdc2-cyclin B kinase complex or mitosis promoting factor (MPF). Checkpoint control mechanisms that monitor essential preparatory events for mitosis, such as DNA replication, are thought to prevent entry into mitosis by downregulating MPF activation until these events are completed. Thus, we were surprised to find that when pronuclear fusion in sea urchin zygotes is blocked with Colcemid, the female pronucleus consistently breaks down before the male pronucleus. This is not due to regional differences in the time of MPF activation, because pronuclei touching each other break down asynchronously to the same extent. To test whether NEB is controlled at the nuclear or cytoplasmic level, we activated the checkpoint for the completion of DNA synthesis separately in female and male pronuclei by treating either eggs or sperm before fertilization with psoralen to covalently cross-link base-paired strands of DNA. When only the maternal DNA is cross-linked, the male pronucleus breaks down first. When the sperm DNA is cross-linked, male pronuclear breakdown is substantially delayed relative to female pronuclear breakdown and sometimes does not occur. Inactivation of the Colcemid after female NEB in such zygotes with touching pronuclei yields a functional spindle composed of maternal chromosomes and paternal centrosomes. The intact male pronucleus remains located at one aster throughout mitosis. In other experiments, when psoralen-treated sperm nuclei, over 90% of the zygote nuclei do not break down for at least 2 h after the controls even though H1 histone kinase activity gradually rises close to, or higher than, control mitotic levels. The same is true for normal zygotes treated with aphidicolin to block DNA synthesis. From these results, we conclude that NEB in sea urchin zygotes is controlled at the nuclear, not cytoplasmic, level, and that mitotic levels of cytoplasmic MPF activity are not sufficient to drive NEB for a nucleus that is under checkpoint control. Our results also demonstrate that the checkpoint for the completion of DNA synthesis inhibits NEB by acting primarily within the nucleus, not by downregulating the activity of cytoplasmic MPF. PMID- 7790348 TI - Nuclear pore complex assembly studied with a biochemical assay for annulate lamellae formation. AB - Formation of the nuclear pore is an intricate process involving membrane fusion and the ordered assembly of up to 1,000 pore proteins. As such, the study of pore assembly is not a simple one. Interestingly, annulate lamellae, a cytoplasmic organelle consisting of stacks of flattened membrane cisternae perforated by numerous pore complexes, have been found to form spontaneously in a reconstitution system derived from Xenopus egg extracts, as determined by electron microscopy (Dabauvalle et al., 1991). In this work, a biochemical assay for annulate lamellae (AL) formation was developed and used to study the mechanism of AL assembly in general and the assembly of individual nucleoporins into pore complexes in particular. Upon incubation of Xenopus egg cytosol and membrane vesicles, the nucleoporins nup58, nup60, nup97, nup153, and nup200 initially present in a disassembled form in the cytosol became associated with membranes and were pelletable. The association was time and temperature dependent and could be measured by immunoblotting. Thin-section electron microscopy as well as negative staining confirmed that annulate lamellae were forming coincident with the incorporation of pore proteins into membranes. Homogenization and subsequent flotation of the membrane fraction allowed us to separate a population of dense membranes, containing the integral membrane pore protein gp210 and all other nucleoporins tested, from the bulk of cellular membranes. Electron microscopy indicated that annulate lamellae were enriched in this dense, pore protein-containing fraction. GTP gamma S prevented incorporation of the soluble pore proteins into membranes. To address whether AL form in the absence of N acetylglucosaminylated pore proteins, AL assembly was carried out in WGA sepharose-depleted cytosol. Under these conditions, annulate lamellae formed but were altered in appearance. When the membrane fraction containing this altered AL was homogenized and subjected to flotation, the pore protein-containing membranes still sedimented in a distinct peak but were less dense than control annulate lamellae. PMID- 7790349 TI - The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an Importin-like protein accumulating in the nucleus at the onset of mitosis. AB - The tumor suppressor gene overgrown hematopoietic organs-31 (oho31) of Drosophila encodes a protein with extensive homology to the Importin protein of Xenopus (50% identity), the related yeast SRP1 protein, and the mammalian hSRP1 and RCH1 proteins. A strong reduction in the expression of oho31 by a P element inserted in the 5' untranslated region of the oho31 transcript or a complete inactivation of oho31 by imprecise P element excision leads to malignant development of the hematopoietic organs and the genital disc, as shown by their growth autonomy in transplantation assays. We have cloned the oho31 gene of Drosophila melanogaster and determined its nucleotide sequence. The gene encodes a phosphoprotein of 522 amino acids made of three domains: a central hydrophobic domain of eight repeats of 42-44 amino acids each, displaying similarity to the arm motif found in junctional and nucleopore complex proteins, and flanked by two hydrophilic NH2- and COOH-terminal domains. Immunostaining revealed that the OHO31 protein is supplied maternally and rapidly degraded during the first 13 nuclear divisions. Thereafter, the OHO31 protein is predominantly expressed, albeit at reduced levels, in proliferating tissues. During the interphase of early embryonic cell cycles, the OHO31 protein is present in the cytoplasm and massively accumulates in the nucleus at the onset of mitosis in late interphase and prophase. The nuclear import of OHO31 is, however, less pronounced during later developmental stages. These results suggest that, similar to Importin, OHO31 may act as a cytosolic factor in nuclear transport. Moreover, the cell cycle-dependent accumulation of OHO31 in the nucleus indicates that this protein may be required for critical nuclear reactions occurring at the onset of mitosis. PMID- 7790351 TI - Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment. AB - Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross-linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf. PMID- 7790350 TI - Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation. AB - We describe the dynamic intracellular localization of Drosophila Pendulin and its role in the control of cell proliferation. Pendulin is a new member of a superfamily of proteins which contains Armadillo (Arm) repeats and displays extensive sequence similarities with the Srp1 protein from yeast, with RAG-1 interacting proteins from humans, and with the importin protein from Xenopus. Almost the entire polypeptide chain of Pendulin is composed of degenerate tandem repeats of approximately 42 amino acids each. A short NH2-terminal domain contains adjacent consensus sequences for nuclear localization and cdc2 kinase phosphorylation. The subcellular distribution of Pendulin is dependent on the phase of cell cycle. During interphase, Pendulin protein is exclusively found in the cytoplasm of embryonic cells. At the transition between G2 and M-phase, Pendulin rapidly translocates into the nuclei where it is distributed throughout the nucleoplasm and the areas around the chromosomes. In the larval CNS, Pendulin is predominantly expressed in the dividing neuroblasts, where it undergoes the same cell cycle-dependent redistribution as in embryos. Pendulin is encoded by the oho31 locus and is expressed both maternally and zygotically. We describe the phenotypes of recessive lethal mutations in the oho31 gene that result in a massive decrease or loss of zygotic Pendulin expression. Hematopoietic cells of mutant larvae overproliferate and form melanotic tumors, suggesting that Pendulin normally acts as a blood cell tumor suppressor. In contrast, growth and proliferation in imaginal tissues are reduced and irregular, resulting in abnormal development of imaginal discs and the CNS of the larvae. This phenotype shows that Pendulin is required for normal growth regulation. Based on the structure of the protein, we propose that Pendulin may serve as an adaptor molecule to form complexes with other proteins. The sequence similarity with importin indicates that Pendulin may play a role in the nuclear import of karyophilic proteins and some of these may be required for the normal transmission and function of proliferative signals in the cells. PMID- 7790353 TI - Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation. AB - The aggregation states of the epidermal growth factor receptor (EGFR) on single A431 human epidermoid carcinoma cells were assessed with two new techniques for determining fluorescence resonance energy transfer: donor photobleaching fluorescence resonance energy transfer (pbFRET) microscopy and fluorescence lifetime imaging microscopy (FLIM). Fluorescein-(donor) and rhodamine-(acceptor) labeled EGF were bound to the cells and the extent of oligomerization was monitored by the spatially resolved FRET efficiency as a function of the donor/acceptor ratio and treatment conditions. An average FRET efficiency of 5% was determined after a low temperature (4 degrees C) incubation with the fluorescent EGF analogs for 40 min. A subsequent elevation of the temperature for 5 min caused a substantial increase of the average FRET efficiency to 14% at 20 degrees C and 31% at 37 degrees C. In the context of a two-state (monomer/dimer) model for the EGFR, these FRET efficiencies were consistent with minimal average receptor dimerizations of 13, 36, and 69% at 4, 20, and 37 degrees C, respectively. A431 cells were pretreated with the monoclonal antibody mAb 2E9 that specifically blocks EGF binding to the predominant population of low affinity EGFR (15). The average FRET efficiency increased dramatically to 28% at 4 degrees C, indicative of a minimal receptor dimerization of 65% for the subpopulation of high affinity receptors. These results are in accordance with prior studies indicating that binding of EGF leads to a fast and temperature dependent microclustering of EGFR, but suggest in addition that the high affinity functional subclass of receptors on quiescent A431 cells are present in a predimerized or oligomerized state. We propose that the transmission of the external ligand-binding signal to the cytoplasmic domain is effected by a concerted relative rotational rearrangement of the monomeric units comprising the dimeric receptor, thereby potentiating a mutual activation of the tyrosine kinase domains. PMID- 7790352 TI - Pseudomonas exotoxin-mediated selection yields cells with altered expression of low-density lipoprotein receptor-related protein. AB - The alpha 2-macroglobulin (alpha 2M) receptor/low-density lipoprotein receptor related protein (LRP) is important for the clearance of proteases, protease inhibitor complexes, and various ligands associated with lipid metabolism. While the regulation of receptor function is poorly understood, the addition of high concentrations of the 39-kD receptor-associated protein (RAP) to cells inhibits the binding and/or uptake of many of these ligands. Previously, we (Kounnas, M.Z., R.E. Morris, M.R. Thompson, D.J. FitzGerald, D.K. Strickland, and C.B. Saelinger. 1992. J. Biol. Chem. 267:12420-12423) [corrected] showed that Pseudomonas exotoxin (PE) could bind immobilized LRP. Also, the addition of RAP blocked toxin-mediated cell killing. These findings suggested that PE might use LRP to gain entry into toxin-sensitive cells. Here we report on a strategy to select PE-resistant lines of Chinese hamster ovary cells that express altered amounts of LRP. An important part of this strategy is to screen PE-resistant clones for those that retain sensitivity to both diphtheria toxin and to a fusion protein composed of lethal factor (from anthrax toxin) fused to the adenosine diphosphate-ribosylating domain of PE. Two lines, with obvious changes in their expression of LRP, were characterized in detail. The 14-2-1 line had significant amounts of LRP, but in contrast to wild-type cells, little or no receptor was displayed on the cell surface. Instead, receptor protein was found primarily within cells, much of it apparently in an unprocessed state. The 14-2-1 line showed no uptake of chymotrypsin-alpha 2M and was 10-fold resistant to PE compared with wild-type cells. A second line, 13-5-1, had no detectable LRP mRNA or protein, did not internalize alpha 2M-chymotrypsin, and exhibited a 100-fold resistance to PE. Resistance to PE appeared to be due to receptor-specific defects, since these mutant lines showed no resistance to a PE chimeric toxin that was internalized via the transferrin receptor. The results of this investigation confirm that LRP mediates the internalization of PE. PMID- 7790354 TI - Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. AB - Our previous results indicated that the plasma membrane of cultured normal rat kidney fibroblastic cell is compartmentalized for diffusion of receptor molecules, and that long-range diffusion is the result of successive intercompartmental jumps (Sako, Y. and Kusumi, A. 1994. J. Cell Biol. 125:1251 1264). In the present study, we characterized the properties of intercompartmental boundaries by tagging transferrin receptor (TR) with either 210-nm-phi latex or 40-nm-phi colloidal gold particles, and by dragging the particle-TR complexes laterally along the plasma membrane using laser tweezers. Approximately 90% of the TR-particle complexes showed confined-type diffusion with a microscopic diffusion coefficient (Dmicro) of approximately 10(-9) cm2/s and could be dragged past the intercompartmental boundaries in their path by laser tweezers at a trapping force of 0.25 pN for gold-tagged TR and 0.8 pN for latex-tagged TR. At lower dragging forces between 0.05 and 0.1 pN, particle-TR complexes tended to escape from the laser trap at the boundaries, and such escape occurred in both the forward and backward directions of dragging. The average distance dragged was half of the confined distance of TR, which further indicates that particle-TR complexes escape at the compartment boundaries. Since variation in the particle size (40 and 210 nm, the particles are on the extracellular surface of the plasma membrane) hardly affects the diffusion rate and behavior of the particle-TR complexes at the compartment boundaries, and since treatment with cytochalasin D or vinblastin affects the movements of TR (Sako and Kusumi as cited above), argument has been advanced that the boundaries are present in the cytoplasmic domain. Rebound of the particle-TR complexes when they escape from the laser tweezers at the compartment boundaries suggests that the boundaries are elastic structures. These results are consistent with the proposal that the compartment boundaries consist of membrane skeleton or a membrane-associated part of the cytoskeleton (membrane skeleton fence model). Approximately 10% of TR exhibited slower diffusion (Dmicro approximately 10(-10)-10(-11) cm2/s) and binding to elastic structures. PMID- 7790355 TI - The 95F unconventional myosin is required for proper organization of the Drosophila syncytial blastoderm. AB - The 95F myosin, a class VI unconventional myosin, associates with particles in the cytoplasm of the Drosophila syncytial blastoderm and is required for the ATP- and F-actin-dependent translocation of these particles. The particles undergo a cell cycle-dependent redistribution from domains that surround each nucleus in interphase to transient membrane invaginations that provide a barrier between adjacent spindles during mitosis. When 95F myosin function is inhibited by antibody injection, profound defects in syncytial blastoderm organization occur. This disorganization is seen as aberrant nuclear morphology and position and is suggestive of failures in cytoskeletal function. Nuclear defects correlate with gross defects in the actin cytoskeleton, including indistinct actin caps and furrows, missing actin structures, abnormal spacing of caps, and abnormally spaced furrows. Three-dimensional examination of embryos injected with anti-95F myosin antibody reveals that actin furrows do not invaginate as deeply into the embryo as do normal furrows. These furrows do not separate adjacent mitoses, since microtubules cross over them. These inappropriate microtubule interactions lead to aberrant nuclear divisions and to the nuclear defects observed. We propose that 95F myosin function is required to generate normal actin-based transient membrane furrows. The motor activity of 95F myosin itself and/or components within the particles transported to the furrows by 95F myosin may be required for normal furrows to form. PMID- 7790356 TI - Actin polymerization and intracellular solvent flow in cell surface blebbing. AB - The cortical actin gel of eukaryotic cells is postulated to control cell surface activity. One type of protrusion that may offer clues to this regulation are the spherical aneurysms of the surface membrane known as blebs. Blebs occur normally in cells during spreading and alternate with other protrusions, such as ruffles, suggesting similar protrusive machinery is involved. We recently reported that human melanoma cell lines deficient in the actin filament cross-linking protein, ABP-280, show prolonged blebbing, thus allowing close study of blebs and their dynamics. Blebs expand at different rates of volume increase that directly predict the final size achieved by each bleb. These rates decrease as the F-actin concentration of the cells increase over time after plating on a surface, but do so at lower concentrations in ABP-280 expressing cells. Fluorescently labeled actin and phalloidin injections of blebbing cells indicate that a polymerized actin structure is not present initially, but appears later and is responsible for stopping further bleb expansion. Therefore, it is postulated that blebs occur when the fluid-driven expansion of the cell membrane is sufficiently rapid to initially outpace the local rate of actin polymerization. In this model, the rate of intracellular solvent flow driving this expansion decreases as cortical gelation is achieved, whether by factors such as ABP-280, or by concentrated actin polymers alone, thereby leading to decreased size and occurrence of blebs. Since the forces driving bleb extension would always be present in a cell, this process may influence other cell protrusions as well. PMID- 7790357 TI - Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle. AB - The three dimensional organization of microtubules in mitotic spindles of the yeast Saccharomyces cerevisiae has been determined by computer-aided reconstruction from electron micrographs of serially cross-sectioned spindles. Fifteen spindles ranging in length from 0.6-9.4 microns have been analyzed. Ordered microtubule packing is absent in spindles up to 0.8 micron, but the total number of microtubules is sufficient to allow one microtubule per kinetochore with a few additional microtubules that may form an interpolar spindle. An obvious bundle of about eight interpolar microtubules was found in spindles 1.3 1.6 microns long, and we suggest that the approximately 32 remaining microtubules act as kinetochore fibers. The relative lengths of the microtubules in these spindles suggest that they may be in an early stage of anaphase, even though these spindles are all situated in the mother cell, not in the isthmus between mother and bud. None of the reconstructed spindles exhibited the uniform populations of kinetochore microtubules characteristic of metaphase. Long spindles (2.7-9.4 microns), presumably in anaphase B, contained short remnants of a few presumed kinetochore microtubules clustered near the poles and a few long microtubules extending from each pole toward the spindle midplane, where they interdigitated with their counterparts from the other pole. Interpretation of these reconstructed spindles offers some insights into the mechanisms of mitosis in this yeast. PMID- 7790358 TI - Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. AB - Correct assembly and function of the mitotic spindle during cell division is essential for the accurate partitioning of the duplicated genome to daughter cells. Protein phosphorylation has long been implicated in controlling spindle function and chromosome segregation, and genetic studies have identified several protein kinases and phosphatases that are likely to regulate these processes. In particular, mutations in the serine/threonine-specific Drosophila kinase polo, and the structurally related kinase Cdc5p of Saccharomyces cerevisae, result in abnormal mitotic and meiotic divisions. Here, we describe a detailed analysis of the cell cycle-dependent activity and subcellular localization of Plk1, a recently identified human protein kinase with extensive sequence similarity to both Drosophila polo and S. cerevisiae Cdc5p. With the aid of recombinant baculoviruses, we have established a reliable in vitro assay for Plk1 kinase activity. We show that the activity of human Plk1 is cell cycle regulated, Plk1 activity being low during interphase but high during mitosis. We further show, by immunofluorescent confocal laser scanning microscopy, that human Plk1 binds to components of the mitotic spindle at all stages of mitosis, but undergoes a striking redistribution as cells progress from metaphase to anaphase. Specifically, Plk1 associates with spindle poles up to metaphase, but relocalizes to the equatorial plane, where spindle microtubules overlap (the midzone), as cells go through anaphase. These results indicate that the association of Plk1 with the spindle is highly dynamic and that Plk1 may function at multiple stages of mitotic progression. Taken together, our data strengthen the notion that human Plk1 may represent a functional homolog of polo and Cdc5p, and they suggest that this kinase plays an important role in the dynamic function of the mitotic spindle during chromosome segregation. PMID- 7790359 TI - Overexpression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. AB - Neurofilaments (NFs), the major intermediate filaments of central nervous system (CNS) and peripheral nervous system (PNS) neurons, are heteropolymers formed from the high (NFH), middle (NFM), and low (NFL) molecular weight NF subunits. To gain insights into how the expression of NF subunit proteins is regulated in vivo, two transgenes harboring coding sequences for human NFM (hNFM) with or without the hNFM multiphosphorylation repeat domain were introduced into mice. Expression of both hNFM constructs was driven by the hNFM promoter and resulted in increased levels of hNFM subunits concomitant with an elevation in the levels of mouse NFL (mNFL) proteins in the CNS of both lines of transgenic mice. The increased levels of mNFL appear specific to NFM because previous studies of transgenic mice overexpressing either NFL or NFH did not result in increased expression of either of the other two NF subunits. Further, levels of the most heavily phosphorylated isoforms of mouse NFH (mNFH) were reduced in the brains of these transgenic mice, and electron microscopic studies showed a higher packing density of NFs in large diameter CNS axons of transgenic versus wild-type mice. Thus, reduced phosphorylation of the mNFH carboxy terminal domain may be a compensatory response of CNS neurons to the increase in NFs, and reduced negative charges on mNFH sidearms may allow axons to accommodate more NFs by increasing their packing density. Taken together, these studies imply that NFM may play a dominant role in the in vivo regulation of the levels of NFL protein, the stoichiometry of NF subunits, and the phosphorylation state of NFH. NFM and NFH proteins may assume similar functions in regulation of NF packing density in vivo. PMID- 7790360 TI - 7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. AB - The prohormone convertase PC2, which is thought to mediate the proteolytic conversion of many peptide hormones, has recently been shown to interact with the neuroendocrine-specific polypeptide 7B2 in Xenopus intermediate lobe (Braks, J. A. M., and G. J. M. Martens. Cell. 78:263. 1994). In the present work we have stably transfected neuroendocrine cell lines with rat 7B2 constructs and found that overexpression of 27 kD 7B2 greatly facilitates the kinetics of maturation of proPC2, both in AtT-20/PC2 cells and in Rin5f cells. The half-life of conversion of proPC2 was reduced from 2.7 to 1.7 h in AtT-20/PC2 cells stably transfected with 27 kD 7B2 cDNA. The previously proposed "chaperone" domain was not sufficient for this facilitation event; however, a construct corresponding to the 21-kD 7B2 protein (which represents the naturally occurring maturation product) functioned well. A 7B2 construct in which maturation of 27 kD 7B2 to its 21-kD form was blocked was unable to facilitate maturation of proPC2. To correlate effects on PC2 maturation with the actual generation of PC2 enzymatic activity, a similar transfection of 21 kD 7B2 was performed using CHO cells previously amplified for the expression of proPC2. Enzymatic activity cleaving the fluorogenic substrate Cbz-Arg-Ser-Lys-Arg-AMC was highly correlated with the expression of immunoreactive 21 kD 7B2 in the conditioned medium; medium obtained from the parent cell line was completely inactive. Enzymatic activity was identified as PC2 on the basis of inhibition by the carboxy-terminal peptide of 7B2, which has previously been shown to represent a potent and specific PC2 inhibitor. Taken together, our in vivo results indicate that the interesting secretory protein 7B2 is a bifunctional molecule with an amino-terminal domain involved in proPC2 transport as well as activation. PMID- 7790361 TI - Chemoattractant and GTP gamma S-mediated stimulation of adenylyl cyclase in Dictyostelium requires translocation of CRAC to membranes. AB - We have previously reported that activation of adenylyl cyclase by chemoattractant receptors in Dictyostelium requires, in addition to a heterotrimeric G-protein, a cytosolic protein, designated CRAC (Lilly, P., and P. N. Devreotes. 1994. J. Biol. Chem. 269:14123-14129; Insall, R. H., A. Kuspa, P. J. Lilly, G. Schaulsky, L. R. Levin, W. F. Loomis, and P. N. Devreotes. 1994. J. Cell Biol. 126:1537-1545). In this report, we show that in intact cells, chemoattractants promote translocation of CRAC from the cytosolic to the membrane fraction. However, CRAC is not required at the time of receptor stimulation; it can be added to lysates of activated cells. Treatment of membranes with guanine nucleotides creates binding sites for CRAC. These binding sites can be generated in mutants lacking each of the components of the pathway except the beta-subunit, suggesting that free or "activated" beta gamma-subunits may be a part of the binding site. This hypothesis is consistent with previous observations that CRAC contains a pleckstrin homology domain and that the beta gamma-subunits likely mediate activation of adenylyl cyclase in this system. Thus, CRAC may serve as an adapter, linking the G-protein beta gamma-subunits to activation of the enzyme. GTP gamma S cannot generate CRAC-binding sites when the adenylyl cyclase pathway has been adapted by prior chemoattractant stimulation, suggesting that this is a point of downstream adaptation. PMID- 7790362 TI - The G protein beta subunit is essential for multiple responses to chemoattractants in Dictyostelium. AB - Increasing evidence suggests that the beta gamma-subunit dimers of heterotrimeric G proteins play a pivotal role in transducing extracellular signals. The recent construction of G beta null mutants (g beta-) in Dictyostelium provides a unique opportunity to study the role of beta gamma dimers in signaling processes mediated by chemoattractant receptors. We have shown previously that g beta- cells fail to aggregate; in this study, we report the detailed characterization of these cells. The g beta- cells display normal motility but do not move towards chemattractants. The typical GTP-regulated high affinity chemoattractant-binding sites are lost in g beta- cells and membranes. The g beta- cells do not display chemoattractant-stimulated adenylyl cyclase or guanylyl cyclase activity. These results show that in vivo G beta links chemoattractant receptors to effectors and is therefore essential in many chemoattractant-mediated processes. In addition, we find that G beta is required for GTP gamma S stimulation of adenylyl cyclase activity, suggesting that the beta gamma-dimer activates the enzyme directly. Interestingly, the g beta- cells grow at the same rate as wild-type cells in axenic medium but grow more slowly on bacterial lawns and, therefore, may be defective in phagocytosis. PMID- 7790363 TI - The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI anchored molecule apparently involved in keratinocyte cell-cell adhesion. AB - The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion. PMID- 7790366 TI - Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. AB - Relatively little is known about the mechanisms used by somatic cells to regulate the replication of the centrosome complex. Centrosome doubling was studied in CHO cells by electron microscopy and immunofluorescence microscopy using human autoimmune anticentrosome antiserum, and by Northern blotting using the cDNA encoding portion of the centrosome autoantigen pericentriolar material (PCM)-1. Centrosome doubling could be dissociated from cycles of DNA synthesis and mitotic division by arresting cells at the G1/S boundary of the cell cycle using either hydroxyurea or aphidicolin. Immunofluorescence micros-copy using SPJ human autoimmune anticentrosome antiserum demonstrated that arrested cells were able to undergo numerous rounds of centrosome replication in the absence of cycles of DNA synthesis and mitosis. Northern blot analysis demonstrated that the synthesis and degradation of the mRNA encoding PCM-1 occurred in a cell cycle-dependent fashion in CHO cells with peak levels of PCM-1 mRNA being present in G1 and S phase cells before mRNA amounts dropped to undetectable levels in G2 and M phases. Conversely, cells arrested at the G1/S boundary of the cell cycle maintained PCM 1 mRNA at artificially elevated levels, providing a possible molecular mechanism for explaining the multiple rounds of centrosome replication that occurred in CHO cells during prolonged hydroxyurea-induced arrest. The capacity to replicate centrosomes could be abolished in hydroxyurea-arrested CHO cells by culturing the cells in dialyzed serum. However, the ability to replicate centrosomes and to synthesize PCM-1 mRNA could be re-initiated by adding EGF to the dialyzed serum. This experimental system should be useful for investigating the positive and negative molecular mechanisms used by somatic cells to regulate the replication of centrosomes and for studying and the methods used by somatic cells for coordinating centrosome duplication with other cell cycle progression events. PMID- 7790364 TI - Membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) and diphtheria toxin receptor-associated protein (DRAP27)/CD9 form a complex with integrin alpha 3 beta 1 at cell-cell contact sites. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family of growth factors, which interact with EGF receptor to exert mitogenic activity. The membrane-anchored form of HB-EGF, proHB-EGF, is biologically active, providing mitogenic stimulation to neighboring cells in a juxtacrine mode. ProHB-EGF forms a complex with diphtheria toxin receptor associated protein (DRAP27)/CD9, a tetra membrane-spanning protein that upregulates the juxtacrine mitogenic activity of proHB-EGF. We explored whether other proteins associate with DRAP27/CD9 and proHB-EGF. Immunoprecipitation with anti-DRAP27/CD9 resulted in preferential coprecipitation of integrin alpha 3 beta 1 from Vero cell, A431 cell and MG63 cell lysates. Anti-integrin alpha 3 or anti integrin beta 1 coprecipitated DRAP27/CD9 from the same cell lysates. Chemical cross-linking confirmed the physical association of DRAP27/CD9 and integrin alpha 3 beta 1. Using Vero-H cells, which overexpress HB-EGF, we also demonstrated the association of proHB-EGF with DRAP27/CD9 and integrin alpha 3 beta 1. Moreover, colocalization of proHB-EGF, DRAP27/CD9, and integrin alpha 3 beta 1 at cell-cell contact sites was observed by double-immunofluorescence staining. At cell-cell contact sites, DRAP27/CD9 was highly coincident with alpha-catenin and vinculin, suggesting that DRAP27/CD9, proHB-EGF, and integrin alpha 3 beta 1 are colocalized with adherence junction-locating proteins. These results indicate that direct interaction of growth factors and cell adhesion molecules may control cell proliferation during the cell-cell adhesion process. PMID- 7790365 TI - Components of the nuclear signaling cascade that regulate collagenase gene expression in response to integrin-derived signals. AB - We have shown previously that the expression of collagenase is upregulated in rabbit synovial fibroblasts cultured on a substrate of antibody to the alpha 5 chain of the alpha 5 beta 1 integrin fibronectin receptor or on the 120-kD cell binding chymotryptic fragment of plasma fibronectin, but remains at basal levels in cells plated on intact plasma fibronectin. We now have identified some of the components of a signaling pathway that couples the fibronectin receptor to the induction of collagenase transcription. We studied the control of collagenase gene expression in cells adhering to the 120-kD fragment of fibronectin, to antifibronectin receptor antibody, or to plasma fibronectin by transiently introducing promoter-reporter constructs into rabbit synovial fibroblasts before plating cells on these matrices. The constructs contained segments of the human collagenase promoter regulating transcription of chloramphenicol acyl transferase. Expression of constructs containing the -1200/-42-bp segment or the 139/-42-bp segment of the collagenase promoter inserted upstream from the reporter gene was induced to similar extents in cells plated on the 120-kD fragment of fibronectin or on anti-fibronectin receptor antibody, relative to that in fibroblasts plated on fibronectin. The expression of the construct containing the -66/-42-bp segment of the promoter was not regulated and was similar to that of the parent pBLCAT2 plasmid, suggesting that the -139/-67 region of the collagenase promoter, which contains PEA3- and AP1-binding sites, regulates the transcription of collagenase caused by integrin-derived signals. Expression of a reporter construct containing only the PEA3 and AP1 sites in the collagenase promoter (-90/-67) also increased in cells plated on the 120-kD fragment of fibronectin or on anti-fibronectin receptor antibody, relative to that in cells plated on fibronectin. Mutations in either the AP1 or PEA3 site of this minimal promoter abrogated its activity in cells plated on these inductive ligands. Expression of c-fos mRNA increased within 1 h of plating cells on the 120-kD fibronectin fragment or on anti-fibronectin receptor antibody, relative to that in cells plated on fibronectin. c-Fos protein accumulated in the nuclei of fibroblasts within 10 min of plating on the 120-kD fibronectin fragment. The increase in c-Fos was required for the increase in collagenase in cells plated on the 120-kD fibronectin fragment: incubation of cells with antisense, but not sense, c-fos oligonucleotides diminished both basal and induced expression of the -139/-42 collagenase promoter-reporter construct and decreased expression of the endogenous collagenase gene.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7790367 TI - Molecular genetic studies of a human epidermal autoantigen (the 180-kD bullous pemphigoid antigen/BP180): identification of functionally important sequences within the BP180 molecule and evidence for an interaction between BP180 and alpha 6 integrin. AB - The 180-kD bullous pemphigoid autoantigen (BP180) is a component of the hemidesmosome, a cell-matrix connector. This protein is oriented in a type II fashion in the membrane of the hemidesmosome and is a hybrid collagen (classified as type XVII). We have analyzed the fate of various mutant BP180 molecules transfected into several different cell types. A protein, D1, lacking the collagen-like extracellular domains of BP180 polarizes normally in 804G epithelial cells and colocalizes with other hemidesmosomal components in the plane of the basal cell surface. However, deletion of a stretch of 36 amino acids located at the NH2 terminus of D1 induces an apical polarization of the protein (D1-36N) in the cell surface of 804G cells. Deletion of the 27-amino acid noncollagenous extracellular domain that is located immediately after the membrane spanning domain of BP180 results in a failure of D1-27C protein to codistribute with other hemidesmosomal components despite its basal localization in transfected 804G cells. In FG cells, which lack their own BP180, transfected D1 protein localizes with the alpha 6 beta 4 integrin heterodimer. In HT1080 cells, which do not possess BP180 or beta 4 integrin, D1 protein localizes with alpha 6 beta 1 integrin while both the D1-27C and D1-36N proteins do not. Moreover, D1 protein coprecipitates with alpha 6 integrin from extracts of HT1080 transfectants. Taken together, these results suggest that the NH2-terminal domain of BP180 determines polarization of BP180 while the noncollagenous extracellular domain of BP180 stabilizes its interactions with other hemidesmosomal components, such as alpha 6 integrin. Perturbation of this latter domain by human bullous pemphigoid autoantibodies may explain the loss of epidermal cell-dermis attachment that characterizes the BP disease. PMID- 7790368 TI - Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. AB - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic polypeptide, distantly related to transforming growth factor-beta (TGF-beta), originally isolated by virtue of its ability to induce dopamine uptake and cell survival in cultures of embryonic ventral midbrain dopaminergic neurons, and more recently shown to be a potent neurotrophic factor for motorneurons. The biological activities and distribution of this molecule outside the central nervous system are presently unknown. We report here on the mRNA expression, biological activities and initial receptor binding characterization of GDNF and a shorter spliced variant termed GDNF beta in different organs and peripheral neurons of the developing rat. Both GDNF mRNA forms were found to be most highly expressed in developing skin, whisker pad, kidney, stomach and testis. Lower expression was also detected in developing skeletal muscle, ovary, lung, and adrenal gland. Developing spinal cord, superior cervical ganglion (SCG) and dorsal root ganglion (DRG) also expressed low levels of GDNF mRNA. Two days after nerve transection, GDNF mRNA levels increased dramatically in the sciatic nerve. Overall, GDNF mRNA expression was significantly higher in peripheral organs than in neuronal tissues. Expression of either GDNF mRNA isoform in insect cells resulted in the production of indistinguishable mature GDNF polypeptides. Purified recombinant GDNF promoted neurite outgrowth and survival of embryonic chick sympathetic neurons. GDNF produced robust bundle-like, fasciculated outgrowth from chick sympathetic ganglion explants. Although GDNF displayed only low activity on survival of newborn rat SCG neurons, this protein was found to increase the expression of vasoactive intestinal peptide and preprotachykinin-A mRNAs in cultured SCG neurons. GDNF also promoted survival of about half of the neurons in embryonic chick nodose ganglion and a small subpopulation of embryonic sensory neurons in chick dorsal root and rat trigeminal ganglia. Embryonic chick sympathetic neurons expressed receptors for GDNF with Kd 1-5 x 10(-9) M, as measured by saturation and displacement binding assays. Our findings indicate GDNF is a new neurotrophic factor for developing peripheral neurons and suggest possible non-neuronal roles for GDNF in the developing reproductive system. PMID- 7790369 TI - Signals and structural features involved in integral membrane protein targeting to the inner nuclear membrane. AB - We have examined transfected cells by immunofluorescence microscopy to determine the signals and structural features required for the targeting of integral membrane proteins to the inner nuclear membrane. Lamin B receptor (LBR) is a resident protein of the nuclear envelope inner membrane that has a nucleoplasmic, amino-terminal domain and a carboxyl-terminal domain with eight putative transmembrane segments. The amino-terminal domain of LBR can target both a cytosolic protein to the nucleus and a type II integral protein to the inner nuclear membrane. Neither a nuclear localization signal (NLS) of a soluble protein, nor full-length histone H1, can target an integral protein to the inner nuclear membrane although they can target cytosolic proteins to the nucleus. The addition of an NLS to a protein normally located in the inner nuclear membrane, however, does not inhibit its targeting. When the amino-terminal domain of LBR is increased in size from approximately 22.5 to approximately 70 kD, the chimeric protein cannot reach the inner nuclear membrane. The carboxyl-terminal domain of LBR, separated from the amino-terminal domain, also concentrates in the inner nuclear membrane, demonstrating two nonoverlapping targeting signals in this protein. Signals and structural features required for the inner nuclear membrane targeting of proteins are distinct from those involved in targeting soluble polypeptides to the nucleoplasm. The structure of the nucleocytoplasmic domain of an inner nuclear membrane protein also influences targeting, possibly because of size constraints dictated by the lateral channels of the nuclear pore complexes. PMID- 7790370 TI - Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. AB - In this paper we used a multiparametric approach to analyze extensively the events occurring during apoptotic cell death of thymocytes, and furthermore, we asked whether alterations in mitochondrial structure and function are occurring in early stages of apoptosis. A multiparametric quantitative analysis was performed on normal or apoptotic thymocytes emerging from a few-hour culture performed in culture medium or in the presence of dexamethasone. Simultaneous detection of light scattering properties, integrity of plasma membrane (trypan blue exclusion), chromatin condensation (AO/EB staining of entire cells or PI staining of nuclei), and DNA fragmentation (in situ nick-translation in apoptotic cells) allowed a precise analysis of the preapoptotic and apoptotic stages. Moreover a thorough study of mitochondrial transmembrane potential (delta psi m) assessed following in a time course study the uptake by apoptotic cells of the cationic lipophilic dye DiOC6(3) or the J-aggregate-forming cation JC-1, indicates that a drop in delta psi m occurs very early in thymocyte apoptosis, before DNA fragmentation. This is associated with alteration in mitochondrial structure assessed by cytofluorimetric study of NAO uptake in apoptotic cells. Finally these dramatic alterations in mitochondrial structure and function occurring in early stages of apoptosis were confirmed by confocal and electron microscopy analysis. PMID- 7790371 TI - Lens epithelial cell apoptosis appears to be a common cellular basis for non congenital cataract development in humans and animals. AB - Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation. PMID- 7790372 TI - Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction. AB - Activation of the PDGF receptor on human arterial smooth muscle cells (SMC) induces migration and proliferation via separable signal transduction pathways. Sphingosine-1-phosphate (Sph-1-P) can be formed following PDGF receptor activation and therefore may be implicated in PDGF-receptor signal transduction. Here we show that Sph-1-P does not significantly affect PDGF-induced DNA synthesis, proliferation, or activation of mitogenic signal transduction pathways, such as the mitogen-activated protein (MAP) kinase cascade and PI 3 kinase, in human arterial SMC. On the other hand, Sph-1-P strongly mimics PDGF receptor-induced chemotactic signal transduction favoring actin filament disassembly. Although Sph-1-P mimics PDGF, exogenously added Sph-1-P induces more prolonged and quantitatively greater PIP2 hydrolysis compared to PDGF-BB, a markedly stronger calcium mobilization and a subsequent increase in cyclic AMP levels and activation of cAMP-dependent protein kinase. This excessive and prolonged signaling favors actin filament disassembly by Sph-1-P, and results in inhibition of actin nucleation, actin filament assembly and formation of focal adhesion sites. Sph-1-P-induced interference with the dynamics of PDGF-stimulated actin filament disassembly and assembly results in a marked inhibition of cell spreading, of extension of the leading lamellae toward PDGF, and of chemotaxis toward PDGF. The results suggest that spatial and temporal changes in phosphatidylinositol turnover, calcium mobilization and actin filament disassembly may be critical to PDGF-induced chemotaxis and suggest a possible role for endogenous Sph-1-P in the regulation of PDGF receptor chemotactic signal transduction. PMID- 7790373 TI - Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects. AB - Proteins in the TGF-beta superfamily transduce their effects through binding to type I and type II serine/threonine kinase receptors. Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 or BMP-7), a member of the TGF-beta superfamily which belongs to the BMP subfamily, was found to bind activin receptor type I (ActR-I), and BMP receptors type IA (BMPR-IA) and type IB (BMPR IB) in the presence of activin receptors type II (ActR-II) and type IIB (ActR IIB). The binding affinity of OP-1 to ActR-II was two- to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR II. These results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins. Some of the known biological effects of activin were observed for OP-1, including growth inhibition and erythroid differentiation induction. Compared to activin, OP-1 was shown to be a poor inducer of mesoderm in Xenopus embryos. Moreover, follistatin, an inhibitor of activins, was found to inhibit the effects of OP-1, if added at a 10-fold excess. However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. OP-1 has overlapping binding specificities with activins, and shares certain but not all of the functional effects of activins. Thus, OP-1 may have broader effects in vivo than hitherto recognized. PMID- 7790374 TI - A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. AB - Degradation of type I collagen, the most abundant collagen, is initiated by collagenase cleavage at a highly conserved site between Gly775 and Ile776 of the alpha 1 (I) chain. Mutations at or around this site render type I collagen resistant to collagenase digestion in vitro. We show here that mice carrying a collagenase-resistant mutant Col1a-1 transgene die late in embryo-genesis, ascribable to overexpression of the transgene, since the same mutation introduced into the endogenous Col1a-1 gene by gene targeting permitted normal development of mutant mice to young adulthood. With increasing age, animals carrying the targeted mutation developed marked fibrosis of the dermis similar to that in human scleroderma. Postpartum involution of the uterus in the mutant mice was also impaired, with persistence of collagenous nodules in the uterine wall. Although type I collagen from the homozygous mutant mice was resistant to cleavage by human or rat fibroblast collagenases at the helical site, only the rat collagenase cleaved collagen trimers at an additional, novel site in the nonhelical N-telopeptide domain. Our results suggest that cleavage by murine collagenase at the N-telopeptide site could account for resorption of type I collagen during embryonic and early adult life. During intense collagen resorption, however, such as in the immediate postpartum uterus and in the dermis later in life, cleavage at the helical site is essential for normal collagen turnover. Thus, type I collagen is degraded by at least two differentially controlled mechanisms involving collagenases with distinct, but overlapping, substrate specificities. PMID- 7790375 TI - Functional characterization of the 180-kD ribosome receptor in vivo. AB - A cDNA encoding the 180-kD canine ribosome receptor (RRp) was cloned and sequenced. The deduced primary structure indicates three distinct domains: an NH2 terminal stretch of 28 uncharged amino acids representing the membrane anchor, a basic region (pI = 10.74) comprising the remainder of the NH2-terminal half and an acidic COOH-terminal half (pI = 4.99). The most striking feature of the amino acid sequence is a 10-amino acid consensus motif, NQGKKAEGAP, repeated 54 times in tandem without interruption in the NH2-terminal positively charged region. We postulate that this repeated sequence represents a ribosome binding domain which mediates the interaction between the ribosome and the ER membrane. To substantiate this hypothesis, recombinant full-length ribosome receptor and two truncated versions of this protein, one lacking the potential ribosome binding domain, and one lacking the COOH terminus, were expressed in Saccharomyces cerevisiae. Morphological and biochemical analyses showed all proteins were targeted to, and oriented correctly in the ER membrane. In vitro ribosome binding assays demonstrated that yeast microsomes containing the full-length canine receptor or one lacking the COOH-terminal domain were able to bind two to four times as many human ribosomes as control membranes lacking a recombinant protein or microsomes containing a receptor lacking the NH2-terminal basic domain. Electron micrographs of these cells revealed that the expression of all receptor constructs led to a proliferation of perinuclear ER membranes known as "karmellae." Strikingly, in those strains which expressed cDNAs encoding a receptor containing the putative ribosome binding domain, the induced ER membranes (examined in situ) were richly studded with ribosomes. In contrast, karmellae resulting from the expression of receptor cDNA lacking the putative ribosome binding domain were uniformly smooth and free of ribosomes. Cell fractionation and biochemical analyses corroborated the morphological characterization. Taken together these data provide further evidence that RRp functions as a ribosome receptor in vitro, provide new evidence indicating its functionality in vivo, and in both cases indicate that the NH2-terminal basic domain is essential for ribosome binding. PMID- 7790376 TI - BiP/Kar2p serves as a molecular chaperone during carboxypeptidase Y folding in yeast. AB - Although transiently associated with numerous newly synthesized proteins, BiP has not been shown to be an essential component directly linked to the folding and oligomerization of newly synthesized proteins in the endoplasmic reticulum. To determine whether it is needed as a molecular chaperone, we analyzed the maturation of an endogenous yeast glycoprotein, carboxypeptidase Y (CPY) in several yeast strains with temperature-sensitive mutations in BiP. These kar2 mutant strains have previously been found to be defective in translocation at the nonpermissive temperature (Vogel, J. P., L. M. Misra, and M. D. Rose, 1990. J. Cell Biol, 110:1885-1895). To circumvent the translocation block, we used DTT at permissive temperature to delay folding and intracellular transport. We then followed the maturation of the ER-retained CPY after shifting to the nonpermissive temperature and dilution of the DTT. Without the functional chaperone, CPY aggregated, failed to be oxidized, and remained in the ER. In contrast to wild-type cells, in which BiP binding was transient with no more than 10-15% of labeled CPY associated at any time, 30-100% of the CPY remained associated with BiP in the mutant strains. In a heterozygous diploid strain, CPY matured and exited the ER normally. Taken together, the results provide clear evidence that BiP plays a critical role as a molecular chaperone in CPY folding. PMID- 7790377 TI - Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. AB - Two peroxisomal targeting signals, PTS1 and PTS2, are involved in the import of proteins into the peroxisome matrix. Human patients with fatal generalized peroxisomal deficiency disorders fall into at least nine genetic complementation groups. Cells from many of these patients are deficient in the import of PTS1 containing proteins, but the causes of the protein-import defect in these patients are unknown. We have cloned and sequenced the human cDNA homologue (PTS1R) of the Pichia pastoris PAS8 gene, the PTS1 receptor (McCollum, D., E. Monosov, and S. Subramani. 1993. J. Cell Biol. 121:761-774). The PTS1R mRNA is expressed in all human tissues examined. Antibodies to the human PTS1R recognize this protein in human, monkey, rat, and hamster cells. The protein is localized mainly in the cytosol but is also found to be associated with peroxisomes. Part of the peroxisomal PTS1R protein is tightly bound to the peroxisomal membrane. Antibodies to PTS1R inhibit peroxisomal protein-import of PTS1-containing proteins in a permeabilized CHO cell system. In vitro-translated PTS1R protein specifically binds a serine-lysine-leucine-peptide. A PAS8-PTS1R fusion protein complements the P. pastoris pas8 mutant. The PTS1R cDNA also complements the PTS1 protein-import defect in skin fibroblasts from patients--belonging to complementation group two--diagnosed as having neonatal adrenoleukodystrophy or Zellweger syndrome. The PTS1R gene has been localized to a chromosomal location where no other peroxisomal disorder genes are known to map. Our findings represent the only case in which the molecular basis of the protein-import deficiency in human peroxisomal disorders is understood. PMID- 7790380 TI - Transport of dendritic microtubules establishes their nonuniform polarity orientation. AB - The immature processes that give rise to both axons and dendrites contain microtubules (MTs) that are uniformly oriented with their plus-ends distal to the cell body, and this pattern is preserved in the developing axon. In contrast, developing dendrites gradually acquire nonuniform MT polarity orientation due to the addition of a subpopulation of oppositely oriented MTs (Baas, P. W., M. M. Black, and G. A. Banker. 1989. J. Cell Biol. 109:3085-3094). In theory, these minus-end-distal MTs could be locally nucleated and assembled within the dendrite itself, or could be transported into the dendrite after their nucleation within the cell body. To distinguish between these possibilities, we exposed cultured hippocampal neurons to nanomolar levels of vinblastine after one of the immature processes had developed into the axon but before the others had become dendrites. At these levels, vinblastine acts as a kinetic stabilizer of MTs, inhibiting further assembly while not substantially depolymerizing existing MTs. This treatment did not abolish dendritic differentiation, which occurred in timely fashion over the next two to three days. The resulting dendrites were flatter and shorter than controls, but were identifiable by their ultrastructure, chemical composition, and thickened tapering morphology. The growth of these dendrites was accompanied by a diminution of MTs from the cell body, indicating a net transfer of MTs from one compartment into the other. During this time, minus-end-distal microtubules arose in the experimental dendrites, indicating that new MT assembly is not required for the acquisition of nonuniform MT polarity orientation in the dendrite. Minus-end-distal microtubules predominated in the more proximal region of experimental dendrites, indicating that most of the MTs at this stage of development are transported into the dendrite with their minus-ends leading. These observations indicate that transport of MTs from the cell body is an essential feature of dendritic development, and that this transport establishes the nonuniform polarity orientation of MTs in the dendrite. PMID- 7790378 TI - Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin. AB - Cadherins are Ca(2+)-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, transmembrane cadherins such as E-, P-, and N-cadherin self-associate, while intracellularly they interact indirectly with the actin based cytoskeleton. Several intracellular proteins termed catenins, including alpha-catenin, beta-catenin, and plakoglobin, are tightly associated with these cadherins and serve to link them to the cytoskeleton. Here, we present evidence that in fibroblasts alpha-actinin, but not vinculin, colocalizes extensively with the N-cadherin/catenin complex. This is in contrast to epithelial cells where both cytoskeletal proteins colocalize extensively with E-cadherin and catenins. We further show that alpha-actinin, but not vinculin, coimmunoprecipitates specifically with alpha- and beta-catenin from N- and E-cadherin-expressing cells, but only if alpha-catenin is present. Moreover, we show that alpha-actinin coimmunoprecipitates with the N-cadherin/catenin complex in an actin-independent manner. We therefore propose that cadherin/catenin complexes are linked to the actin cytoskeleton via a direct association between alpha-actinin and alpha catenin. PMID- 7790379 TI - Non-muscle alpha-dystroglycan is involved in epithelial development. AB - The dystroglycan complex is a transmembrane linkage between the cytoskeleton and the basement membrane in muscle. One of the components of the complex, alpha dystroglycan binds both laminin of muscle (laminin-2) and agrin of muscle basement membranes. Dystroglycan has been detected in nonmuscle tissues as well, but the physiological role in nonmuscle tissues has remained unknown. Here we show that dystroglycan during mouse development in nonmuscle tissues is expressed in epithelium. In situ hybridization revealed strong expression of dystroglycan mRNA in all studied epithelial sheets, but not in endothelium or mesenchyme. Conversion of mesenchyme to epithelium occurs during kidney development, and the embryonic kidney was used to study the role of alpha-dystroglycan for epithelial differentiation. During in vitro culture of the metanephric mesenchyme, the first morphological signs of epithelial differentiation can be seen on day two. Northern blots revealed a clear increase in dystroglycan mRNA on day two of in vitro development. A similar increase of expression on day two was previously shown for laminin alpha 1 chain. Immunofluorescence showed that dystroglycan is strictly located on the basal side of developing kidney epithelial cells. Monoclonal antibodies known to block binding of alpha-dystroglycan to laminin-1 perturbed development of epithelium in kidney organ culture, whereas control antibodies did not do so. We suggest that the dystroglycan complex acts as a receptor for basement membrane components during epithelial morphogenesis. It is likely that this involves binding of alpha-dystroglycan to E3 fragment of laminin 1. PMID- 7790381 TI - Antiprogestins inhibit growth and stimulate differentiation in the normal mammary gland. AB - Antiprogestins possess a potent antitumor activity in hormone-dependent experimental breast cancer models. Though the underlying mechanism is not clear, induction of functional differentiation seems to be a major event. This study attempts to test directly for antiproliferative and differentiation promoting activities of antiprogestins on the normal mammary gland. To this end, whole organ cultures of mammary glands from estradiol/progesterone-primed virgin mice maintained in a serum-free medium with aldosteron, prolactin, insulin, and hydrocortisone were exposed to the antiprogestin ZK114043. A 4-day treatment of organ cultures led to a strong inhibition of epithelial DNA synthesis. In parallel, ZK114043 caused alveolar cells to acquire a more differentiated phenotype distinguished by secretory active alveoli composed of single cell layers with increased fat droplet accumulation and enhanced expression of the milk proteins beta-casein and whey acidic protein (WAP). Particularly strong effects were found on the expression of mammary-derived growth inhibitor (MDGI). Both half-maximal inhibition of epithelial DNA synthesis and stimulation of MDGI mRNA expression were found at about 5 ng/ml of ZK114043. Presence in the medium of 5 micrograms/ml hydrocortisone rendered antiglucocorticoid effects of ZK114043 highly unlikely. Furthermore, prevention of action of ZK114043 by the progesterone agonist R5020 and ZK114043 stimulated expression of beta-casein and MDGI mRNA in cultured glands of 10-week-old unprimed virgin mice suggest a progesterone receptor-mediated mechanism of antiprogestin action. Two other antiprogestins, Mifepristone and Onapristone, likewise stimulated MDGI expression. The data provide direct evidence that antiprogestins act like a differentiation factor in the normal mammary gland. PMID- 7790386 TI - Role of protein kinase C alpha in the induction of carcinoembryonic antigen by transforming growth factor beta 1. AB - Previous studies showed that transforming growth factor beta 1 (TGF beta 1) regulates the expression of carcinoembryonic antigen (CEA) and CEA-cross-reactive glycoproteins (CEA-GLYs) in human colon carcinoma cells through a signal transducing pathway associated with protein kinase C (PKC) (Chakrabarty, J. Cell. Physiol., 1992, 152:494-499). In this study we determined the role of the PKC alpha isoform in the regulation of CEA and CEA-GLYs expression by TGF beta 1. Expression of PKC alpha antisense RNA, through transfection experiments with an antisense PKC alpha expression vector, resulted in down-modulation of PKC alpha RNA and protein expression. TGF beta 1 was unable to stimulate the expression and secretion of CEA in cells in which the expression of PKC alpha protein was substantially reduced. The ability of TGF beta 1 to stimulate the expression of the 95- and 55-kDa CEA-GLYs, however, was not affected. We therefore conclude that TGF beta 1 regulates the secretion and expression of CEA through a signal transducing pathway associated with PKC alpha. TGF beta 1 may also regulate the expression of CEA-GLYs through signal-transducing pathways associated with other PKC isoforms. PMID- 7790387 TI - Esterification of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid into the phospholipids of human peripheral blood mononuclear cells: inhibition of the proliferative response. AB - 12-hydroxy-eicosatetraenoic acid (12-HETE), the lipoxygenase metabolite of arachidonic acid produced by activated platelets, has been shown to accumulate in peripheral blood mononuclear cells (PBMC) of elderly people. 12-HETE being antimitogenic for lymphocytes, its accumulation in blood cells might be involved in the well-known decline in immune function which accompanies aging. Because HETEs have been shown to be rapidly metabolized and/or incorporated into cellular lipids in a variety of cell types, we have investigated the uptake, metabolism, and intracellular distribution of exogenous 12-HETE by human PBMC. [3H]-12-HETE was dose and time dependently incorporated by PBMC and also metabolized to more polar products. These polar metabolites were mainly released extracellularly and only marginally esterfied in phospholipids. Although [3H]-12-HETE radiolabel was preferentially associated with phosphatidylcholine, especially after prolonged labeling incubations or following successive short labeling pulses, a substantial amount of radiolabel was also found associated with phosphatidylinositol (20-50% of the labeled phospholipids). The stability of 12-HETE in the phospholipid pool was comparable to that reported for most other cell types, with 50% of the initial radiolabel being still present after 18 hr. Upon exposure to mitogenic activation, 12-HETE-labeled PBMC released unmodified 12-HETE from phosphatidylinositol. In addition, 12-HETE dose dependently inhibited the proliferative response of PBMC to Con A stimulation. These results suggest that 12-HETE esterification in phospholipids might lead to the generation of unusual lipid second messengers with impaired capacity to transduce activation signals, thus decreasing lymphocyte function. PMID- 7790382 TI - Perturbation of the platelet-derived growth factor receptor signaling by dibutyryl-cAMP in human astrocytoma cells. AB - It has been shown that cAMP may perturb the polypeptide growth factor-induced nuclear events. However, the possible interactions of the cAMP-protein kinase A (cAMP-PKA) and receptor tyrosine kinase pathways in the cytosol have not been fully elucidated. In this study, we use human astrocytoma cells as a model to investigate this issue. The results show that platelet-derived growth factor (PDGF)-induced receptor autophosphorylation in human astrocytoma cells is suppressed by dibutyryl-cAMP pretreatment and such suppression is not due to changes in the ligand-receptor binding properties. Further studies show that PDGF induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3-kinase (PI 3-kinase) are also suppressed in dibutyryl-cAMP pretreated cells. The suppression of PLC-gamma 1 tyrosine phosphorylation was accompanied by a decreased production of water soluble inositol phosphates. In contrast, similar treatment with normal human astrocytes potentiates the tyrosine phosphorylation of PLC-gamma 1 and PI 3-kinase. The results indicate that cAMP can either negatively or positively modulate the PDGF receptor tyrosine kinase activity depending on the cell types examined. PMID- 7790384 TI - Regulation of multidrug resistance gene mdr1b/mdr1 expression in isolated mouse uterine epithelial cells. AB - The mammalian uterine epithelium (UE) undergoes drastic physiological and morphological changes during pregnancy. Steady-state levels of murine mdr1b mRNA, transcribed from a multidrug resistance gene encoding a membrane protein which functions as a transporter of lipophilic cytotoxic agents, are low in nonpregnant, cycling UE, but drastically increase (about 1,500- to 2,000-fold) at day 8 of gestation. At day 16 of gestation, levels of mdr1b mRNA are 2,500- to 3,000-fold higher than those in the cycling UE cells. Levels of mdr1b mRNA were elevated to levels comparable to those observed during pregnancy, in the UE of ovariectomized mice following 5-8 days of estrogen and progesterone administration. Withdrawal of these hormones resulted in a drastic reduction of mdr1b mRNA within 36 hr. These results suggested that steroid hormones alone can account for increased mdr1b mRNA expression and do not require the presence of other placenta/embryo-derived factors. Moreover, the hormonal effect on uterine mdr1b mRNA biosynthesis during pregnancy apparently is a delayed phenomenon. Nuclear run-on assays demonstrated that the rate of mdr1b transcription in UE cells prepared from 15-day pregnant mice (d-15 UE cells) was about two- to three fold higher than that in nonpregnant UE cells. This increased transcription rate alone cannot account for mdr1b mRNA accumulation during pregnancy. mdr1b mRNA expression was investigated in primary cultures of d-15 UE cells. mdr1b mRNA levels decayed by 50% within 3-4 hr of culture and reached a steady-state 0.5-2% of initial levels by 24 hr. The rate of mdr1b mRNA decay in primary d-15 UE cells was decreased by treatment with alpha-amanitin or cycloheximide, suggesting that the decay pathway requires both transcription and de novo protein synthesis. Our results suggest that multiple mechanisms are involved in the maintenance of the high levels of mdr1b mRNA in pregnant UE cells. Furthermore, these data suggest that increased mRNA stability may contribute to the accumulation of mdr1b transcript during pregnancy. PMID- 7790383 TI - Effects of hypotonic and hypoionic media on drug pumping by P-glycoprotein expressed in epithelial and nonepithelial cell lines. AB - The effects of anisotonic and anisoionic media on the drug-pumping function of P glycoprotein (Pgp) were studied in epithelial and nonepithelial cells. We used HT 29 colon cells (HT-29/Pgp-) induced to express Pgp and MDR phenotype (HT-29/Pgp+) and NIH3T3 (3T3/Pgp-) cells which were stably transfected with human MDR1 DNA (3T3/Pgp+). Intracellular concentrations of rhodamine 123 (R-123) preloaded into cells were monitored as a function of time by fluorescence imaging microscopy, while cells were superfused with media of different tonicity and/or ionic strength. Efflux was analyzed by a single exponential decay function. In all media tested efflux was considerably higher in Pgp+ than Pgp- cells. In both HT 29 and 3T3 cells loaded with dye in isotonic conditions, dye efflux was not significantly different whether it was measured in isoionic-isotonic (130 mM NaCl, 300 mOsm), hypoionic-isotonic (87 mM NaCl), or hypoionic-hypotonic (200, 150, or 100 mOsm) media throughout the entire experiment or whether the media were changed during the experiment. Similar results were obtained when cells were preincubated and preloaded with dye under hypotonic conditions. Under extreme hypotonic and hypoionic challenge (changing from 130 mM NaCl-300 mOsm to 43 mM NaCl-100 mOsm medium), 3T3 cells, but not HT-29 cells, underwent marked shape and size changes which reduced R-123 cell-associated fluorescence. The changes were most conspicuous in Pgp+ cells, possibly reflecting a Pgp effect on the osmotic or osmoregulatory properties of the cells. However, drug-pumping activity remained essentially unimpaired even under the most extreme hypotonic/hypoionic conditions. PMID- 7790385 TI - Evidence for a pertussis toxin sensitive calcium entry pathway in thyroid FRTL-5 cells. AB - Receptor-mediated calcium entry was investigated in Fura 2 loaded FRTL-5 cells. The purinergic agonist ATP activated the release of sequestered calcium and the entry of extracellular calcium. Downregulation of protein kinase C (PKC) substantially enhanced the ATP-evoked calcium entry. Pretreatment of the cells with pertussis toxin (Ptx) decreased the ATP-evoked calcium entry by 56% and the release of sequestered calcium by 34%. In PKC-downregulated cells, the effect of Ptx treatment on the ATP-evoked increase in [Ca2+]i was 73% and 44%, respectively. Phorbol myristic acetate (PMA) decreased the ATP-evoked calcium entry to the same extent as Ptx. In Ptx-treated cells, the ATP-evoked influx of 45Ca2+ was attenuated. Stimulation of the cells with P2p-purinergic agonist GTP evoked no entry of calcium, although GTP released the same amount of sequestered calcium as did ATP. PKC downregulation or pretreatment with Ptx had no effects on the GTP-evoked responses, whereas PMA decreased the GTP-evoked release of calcium. We conclude that the ATP-activated rapid calcium entry pathway is a second messenger-operated calcium channel. PMID- 7790388 TI - Phenotypically and karyotypically distinct Madin-Darby canine kidney cell clones respond differently to alkaline stress. AB - We isolated two cell clones from the wild-type Madin-Darby canine kidney cell line (MDCK) that resembles renal collecting duct epithelium. Morphology and karyotypes of the two cell clones were evaluated. The MDCK-C7 cell clone morphologically resembles principal cells (polygonal cell shape, flat), while the MDCK-C11 clone resembles intercalated cells (cuboidal cell shape, high). The diploid chromosome number of MDCK-C7 cells is 83.1 +/- 0.2 (n = 139); that for MDCK-C11 cells is 78.8 +/- 0.1 (n = 128). Culture of MDCK-C7 cells in alkaline medium (pH 7.7) induced irreversible phenotypical and genotypical alterations. Transformed MDCK-C7F cells are characterized by two abnormal (biarmed) chromosomes. In contrast, MDCK-C11 cells are not phenotypically altered by alkaline stress. In order to elucidate the role of intracellular pH (pHi) in the transformation process, we measured pHi under control conditions (pH 7.4), after 5 min exposure to alkaline stress ("acute experiment," pH 7.7) and after incubation of the cells in alkaline medium for two weeks ("chronic experiment," pH 7.7). Under control conditions, MDCK-C7 cells maintained pHi at 7.14 +/- 0.01 (n = 154) and MDCK-C11 cells at 7.01 +/- 0.01 (n = 147). Acute alkaline stress increased pHi of both cell types to similar steady-state values. Under chronic alkaline stress, MDCK-C7 cells were unable to maintain intracellular pH within normal limits exhibiting sustained alkalinization, whereas MDCK-C11 cells could successfully regulate pHi. We conclude that wild-type MDCK cells consist of two genetically distinct subpopulations with different morphology and function. Only the MDCK-C7 clone that resembles the principle cell type of renal collecting duct can be transformed by alkaline stress while the MDCK-C11 clone resists this treatment, due to efficient pHi control mechanisms. PMID- 7790389 TI - Repression of tissue inhibitor of matrix metalloproteinase expression by all trans-retinoic acid in rat bone cell populations: comparison with transforming growth factor-beta 1. AB - Retinoids and transforming growth factor-beta 1 (TGF-beta 1) reduce the transcriptional activation of matrix metalloproteinases (MMPs) and increase the expression of the specific tissue inhibitor of MMPs (TIMP-1) in fibroblasts. In contrast, all-trans-retinoic acid (retinoic acid) increases MMP expression in osteoblasts. Therefore, the mechanistic aspects of TIMP-1 regulation by retinoic acid in primary cultures of rat calvarial bone cell populations were studied and compared with those of TGF-beta 1 to determine if modulation of TIMP-1 would augment MMP expression. Retinoic acid was found to reduce TIMP-1 mRNA levels after 24 and 72 hr of culture by up to 60% in a dose-dependent manner. Maximal inhibition occurred at 10(-6) M retinoic acid with half maximal repression at approximately 5 x 10(-8) M. To determine the half life of TIMP-1 mRNA, the specific RNA polymerase II inhibitor DRB was added to cultures and the chase RNA analyzed by slot blots. TIMP-1 mRNA had a half life of approximately 14 hr and this was unaltered by retinoic acid treatment, suggesting that retinoic acid exerts its effects on TIMP-1 transcriptionally. When retinoic acid was added to cycloheximide-treated cultures TIMP-1 mRNA levels were reduced at 5 hr compared with controls. This showed that ongoing protein synthesis was not required to mediate the retinoic acid repression of TIMP-1 mRNA levels and supports the evidence that retinoic acid acts at the transcriptional level to reduce TIMP-1 expression. In contrast, TGF-beta 1 increased TIMP-1 mRNA levels by 3.5-fold at 24 hr to > 10-fold at 72 hr without alterations in mRNA stability indicating that transforming growth factor (TGF)-beta 1 also acts at the transcriptional level to upregulate TIMP-1 expression in bone cells. Thus, these studies have revealed that TIMP-1 regulation by retinoic acid is different in osteoblasts from other cells and that retinoic acid has the property of generating resorptive and formative cell phenotypes in a tissue-specific manner. In bone, reduced TIMP-1 expression would favor bone matrix degradation and bone resorption that is a characteristic action of retinoids. PMID- 7790391 TI - Hepatocyte growth factor is involved in formation of osteoclast-like cells mediated by clonal stromal cells (MC3T3-G2/PA6). AB - Osteoclast formation from hemopoietic precursors has been shown to require the support of stromal cells in bone tissue. In this study, we demonstrated that hepatocyte growth factor (HGF) is one of the stromal cell-derived molecules responsible for osteoclast-like cell formation. For our experiments, we used a coculture system for osteoclastic cell formation and activation in which hemopoietic blast cells are cocultured with calvaria-derived stromal MC3T3-G2/PA6 (PA6) cells on dentine slices in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Addition of anti-HGF neutralizing IgG to the cocultures inhibited the formation of osteoclastic cells and their dentine-resorbing activity. We detected a single 6.0-kb transcript for HGF in PA6 cells, and also recognized immunoreactive M(r) 81,000 and 88,000 forms of HGF in conditioned medium (CM) from PA6 cell cultures, the level of which reached 6 ng/ml. Both the CM and HGF stimulated the proliferation of blast cells synergistically with granulocyte macrophage colony-stimulating factor, resulting in an increased number of osteoclast precursors that respond to 1,25(OH)2D3 that are tartrate-resistant acid phosphatase-positive multinucleate cells in stromal cell-free blast cell cultures in plastic wells. The effect of the CM was diminished by the addition of anti-HGF IgG. However, neither the CM nor HGF stimulated the formation of osteoclastic cells and pits on dentine slices in the absence of PA6 cells. These results suggest that although HGF cannot completely replace stromal cells, it is one of the paracrine mediators produced by stromal cells that act on proliferation of osteoclastic cell precursors. PMID- 7790390 TI - Proteoglycan biosynthesis is required in BC3H1 myogenic cells for modulation of vascular smooth muscle alpha-actin gene expression in response to microenvironmental signals. AB - Induction of vascular smooth muscle (VSM) alpha-actin mRNA expression during cytodifferentiation of mouse BC3H1 myogenic cells coincides with the accumulation of cell surface- and extracellular matrix-associated sulfated proteoglycans. Inhibition of proteoglycan biosynthesis in myogenic cells using an artificial beta-D-xyloside glycosaminoglycan acceptor was accompanied by a reduction in cell surface/extracellular matrix proteoglycans and VSM alpha-actin mRNA expression while enhancing the secretion of free chondroitin sulfate/dermatan sulfate and heparan sulfate glycosaminoglycans into the culture medium. Maximum inhibition of VSM alpha-actin mRNA expression required that proteoglycan biosynthesis be blocked during the early phase of cytodifferentiation when myoblasts were fully confluent and quiescent. The inhibitory effect of beta-D-xyloside on alpha-actin mRNA expression resulted from attenuation at both the transcriptional and post transcriptional control points. Sustained proteoglycan biosynthesis was required for induction of VSM alpha-actin mRNA in quiescent myoblasts in response to cytodifferentiation-permissive, substrate-associated macromolecules (SAM) or upon exposure to soluble serum factors capable of transiently stimulating VSM alpha actin gene transcription. The results suggested that efficient myoblast cytodifferentiation and modulation of VSM alpha-actin mRNA levels depended on intact cell surface proteoglycans to convey signals generated as a consequence of cellular interaction with substrate components and serum factors. PMID- 7790392 TI - Ca(2+)-ATPase inhibitor, cyclopiazonic acid, releases Ca2+ from intracellular stores in RBL-2H3 mast cells and activates a Ca2+ influx pathway that is permeable to sodium and manganese. AB - Cyclopiazonic acid has been reported to inhibit the Ca(2+)-ATPase of intracellular calcium stores in some nonexcitable cell types, such as myeloid cells and lymphocytes. The present study examines the effects of cyclopiazonic acid on rat basophilic leukemia (RBL) cells, a mucosal mast cell line. Addition of cyclopiazonic acid to fura-2-loaded RBL cells evoked a biphasic increase in free ionized intracellular calcium. Release of stored calcium accounted for the first phase of this response. The second phase was determined to be calcium entering through an influx pathway activated by cyclopiazonic acid. The influx pathway was selective for calcium, but was somewhat permeable to manganese. However, in a Ca(2+)-free solution containing EGTA, sodium ions permeated freely. This influx pathway appears to be identical to that which is activated by antigen, the physiological stimulus to the cells. Cyclopiazonic acid also induced secretion when combined with the phorbol ester 12-O-tetradecanoyl phorbol 13 acetate, which activates protein kinase C. PMID- 7790393 TI - Insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the platelet-derived growth factor receptor. AB - R- cells are 3T3-like cells derived from mouse embryos in which the insulin-like growth factor I (IGF-I) receptor (IGF-IR) genes have been disrupted by targeted homologous recombination. These cells cannot grow in serum-free medium supplemented by the growth factors that sustain the growth of other 3T3 cell lines, and cannot be transformed by oncogenes that easily transform wild type mouse embryo cells. We have used these cells to study the role of the IGF-IR in the growth and transformation of cells overexpressing the platelet-derived growth factor (PDGF)-beta beta receptor. We report that an overexpressed PDGF-beta beta receptor fails to induce mitogenesis or transformation in cells lacking the IGF IR, while capable of doing so in cells expressing the IGF-IR. We conclude that the ability of the activated PDGF-beta beta receptor to stimulate cell proliferation and transformation requires a functional IGF-IR. PMID- 7790394 TI - Regulation of AP-3 enhancer activity during hematopoietic differentiation. AB - Phorbol ester treatment of the human leukemic cell line U937 induces macrophage differentiation over 24-48 hr. This differentiation is mediated by the activation and/or repression of specific gene transcription by proteins, enhancer binding factors, that bind to the DNA upstream of the start site of transcription. We find that differentiation of U937 cells induced by phorbol esters and bryostain 1, activators of protein kinase C, and the phosphatase inhibitor, okadaic acid, stimulates transcription from an enhancer sequence which contains multimerized AP 3 binding sequences but not from one that contains multimerized AP-2 binding motifs. Electrophoretic mobility shift assays (EMSA) demonstrate that AP-3 DNA binding activity peaks at 24 hr, remains elevated for 24 hr, and then decreases thereafter. Southwestern blotting demonstrates that the AP-3 enhancer sequence binds to a 48 kDa protein present in these leukemic cells. Because the AP-3 oligomer also contains an overlapping NF-kappa B-like site, the role of NK-kappa B proteins in regulating transcription from this multimerized oligonucleotide was investigated. Transfection of U937 cells with NF-kappa B family members demonstrated activation of AP-3-mediated transcription by rel A but little effect induced by NFKB1 and c-rel. It is unlikely, however, that phorbol ester-induced transcription from this AP-3 sequence is solely mediated by this NF-kappa B family member since treatment of U937 cells with antisense rel A oligodeoxynucleotides did not block phorbol ester-mediated transcription from the AP-3 site. These data demonstrate that AP-3, but not AP-2 sequences, functions to activate mRNA transcription during phorbol ester-induced hematopoietic differentiation and suggests a complex interaction between NF-kappa B and AP-3 proteins in the regulation of this enhancer element. PMID- 7790395 TI - Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide. AB - Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS 18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS 18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18 induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10 fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression. PMID- 7790396 TI - Effect of heparin on bovine epithelial lens cell proliferation induced by heparin affin regulatory peptide. AB - HARP (heparin affin regulatory peptide) is an 18 kDa heparin binding protein, also known as HB-GAM or pleiotrophin (PTN) which has been primarily isolated from brain and uterus, and displays neurite outgrowth, angiogenic and mitogenic activities. Previously, we have expressed the human cDNA encoding human HARP in NIH 3T3 cells. Purified recombinant HARP displayed mitogenic activity for endothelial cells. Its NH2-terminal sequence indicates that the HARP molecule possesses a three amino acid extension from the signal peptide more than the NH2 terminal described. For HB-GAM or PTN, these three amino acids may be essential for the stability and the mitogenic activity of this growth factor. In an attempt to further study the mode of action of this growth factor, we have investigated the mitogenic effect of HARP on various cell types. In contrast to FGF-2, HARP failed to induce stimulation of DNA synthesis on a CCL39 cell line. However, we found that in quiescent bovine epithelial lens (BEL) cells, the stimulation of DNA synthesis induced by HARP is dose-dependent (EC50: 2.5 ng/ml) and maximal stimulation is as potent as that induced by FGF-2 (EC50: 25 pg/ml). Interestingly, when BEL cells were allowed to quiesce in the presence of serum, the stimulation induced by HARP is considerably less potent. In this highly responsive cell system, heparin could potentiate the mitogenic activity of HARP at very low doses (0.1-1 microgram/ml) and inhibit this activity at concentrations of 10 micrograms/ml. In contrast to its protective effect on FGF-1 and -2, heparin was unable to preserve HARP from tryptic and chymotryptic degradations. PMID- 7790397 TI - Bone marrow stromal cells selectively stimulate the rapid expansion of lineage restricted myeloid progenitors. AB - Bone marrow stromal cells serve hematopoietic microenvironments where different blood cells are controlled in their growth and differentiation. To characterize functions of stromal cells, 33 bone marrow stromal cells including preadipocytes, endothelial cells, and fibroblasts were established from transgenic mice harboring temperature-sensitive SV40 T-antigen gene and their selective stimulatory abilities to support large colony formation of lineage-specific hematopoietic progenitor cells (erythroid, monocyte/macrophage, granulocyte, and monocyte-granulocyte) were examined. Among established stromal cells, 27 clones showed erythropoietic stimulatory activity in the presence of erythropoietin. On myeloid progenitors, the stromal cells showed lineage-restricted stimulatory activity and a reciprocal relationship was observed between granulocyte formation and macrophage formation, but these activities were not dependent on the amount of produced colony-stimulating factors (CSFs). Our present study with many stromal cells established from bone marrow indicated that each stromal cell in the bone marrow may provide the preferable microenvironment for a rapid expansion of the lineage-restricted progenitor cells in combination with CSFs. PMID- 7790398 TI - Alterations in the molecular response to DNA damage during cellular aging of cultured fibroblasts: reduced AP-1 activation and collagenase gene expression. AB - Transcriptional activation of c-fos in response to both serum stimulation and DNA damage requires the serum response element. The inability of in vitro aged or senescent fibroblasts to proliferate in response to serum has been shown to be associated with repressed c-fos expression and reduced AP-1 binding activity. In contrast, we have observed similar levels of c-fos mRNA and protein expression in young (early passage) and old (late passage) cells following their treatment with ultraviolet (UV) irradiation or methyl methanesulfonate (MMS). Thus, the early events in the signal transduction pathway leading to transcriptional activation of c-fos following DNA damage are distinct from those mediating the gene's expression in response to mitogenic stimulation. Despite normal levels of c-fos expression, we observed a reduced level of AP-1 binding activity in old cells relative to young cells treated with UV irradiation or MMS. Reduced AP-1 binding activity is associated with reduced expression of the AP-1-dependent gene, collagenase, in old cells treated with DNA damaging agents. Since other DNA damage-inducible genes also contain an AP-1 regulatory element presumed to play a role in their expression, reduced AP-1 binding activity is likely to have a major impact on the old cell's ability to respond appropriately to DNA damage. PMID- 7790399 TI - Apoptosis during HL-60 cell differentiation is closely related to a G0/G1 cell cycle arrest. AB - The cell cycle-associated differences in the susceptibility to apoptosis were examined in HL-60 cells before and after differentiation with phorbol 12, 13 dibutyrate (PDBu). HL-60 cells in various phases of the cell cycle were separated by the counterflow centrifugal elutriation and the susceptibility to apoptosis was measured by the morphological examination and by DNA fragmentation assay. Undifferentiated HL-60 cells in S phase showed a significantly higher susceptibility to apoptosis than those in G0/G1 or G2/M phase either in the absence or presence of apoptosis-inducing reagents such as A23187, actinomycin D (Act D), and cycloheximide (CHX). In contrast, PDBu-treated HL-60 cells preferentially underwent apoptosis in G0/G1 phase. When untreated HL-60 cells enriched for G0/G1 phase were recultured in a complete medium, the percentage of apoptotic cells increased after 6-12 h in correlation with the increase in S phase cells. When the same experiment was performed with PBDu-treated cells, spontaneous increase of apoptotic cells was observed while almost all cells remained in G0/G1 phase. Northern blot analysis revealed that undifferentiated cells expressed the same amounts of bcl-2 mRNA in each cell cycle phase, whereas G0/G1-predominant reduction of bcl-2 mRNA was noted in PDBu-treated cells. There was no difference in the amounts of CD11b mRNA between G0/G1 fraction and S+G2/M fraction of differentiated HL-60 cells. BCL-2 overexpression could almost completely abrogate the G0/G1-predominant induction of apoptosis in differentiated HL-60 cells. These results suggest that G0/G1 cell cycle arrest and down-regulation of bcl-2 mRNA in G0/G1 phase might be associated with apoptosis in differentiated HL-60 cells whereas the weakness of chromatin structure in S phase might be related to apoptosis in undifferentiated HL-60 cells. PMID- 7790400 TI - Negative regulation of a special, double AP-1 consensus element in the vimentin promoter: interference by the retinoic acid receptor. AB - The growth-regulated vimentin gene contains a functional double AP-1 binding site formed by two nearly perfect inverted repeats. We present evidence for down regulation of vimentin expression by the retinoic acid receptor (RAR) in two mesodermally derived cell types. By mutation analysis we prove that the double consensus element is responsible for this negative regulation. From in vitro protein-DNA interaction studies we conclude that AP-1 binding is inhibited at RAR amounts required for occupation of the cognate RAR binding site in nuclear extracts from 3T3 cells and differentiated embryonal carcinoma cells. Furthermore, we show that, unlike in other cases, trans-activation of the vimentin AP-1 enhancer element can occur in undifferentiated embryonal carcinoma cells, despite the low amount of Jun and Fos proteins present in these cells. Here, however, down-regulation by retinoic acid cannot be detected. PMID- 7790401 TI - Use of a new fluorescent probe, seminaphthofluorescein-calcein, for determination of intracellular pH by simultaneous dual-emission imaging laser scanning confocal microscopy. AB - A new pH indicator, seminaphthofluorescein (SNAFL)-calcein acetoxymethyl ester, was used for intracellular pH (pHi) measurement in living MDCK cells with a laser scanning confocal microscope (LSCM) equipped with an Argon/Krypton laser and dual excitation and dual-emission (FITC/Texas Red) filter set. SNAFL-calcein excitation maxima are approximately 492/540 nm (acid/base) and emission maxima are approximately 535/625 nm (acid/base) with a pKa value at approximately 7.0. The absorption/emission spectra of SNAFL-calcein indicate that the ratio of emission intensities of its basic/acidic forms is pH dependent. With an Argon/Krypton LSCM, we were able to monitor the acidic and basic forms of this dye simultaneously using dual-excitation (488/568 nm) and dual-emission (525-614 nm/> or = 615 nm) wavelengths (lambda s). The simultaneous dual excitation/emission LSCM system allows for efficient recording of pHi dynamics (time resolution approximately 1 sec) in living cells. We have analyzed emission stability of the dye at different temperatures (22 degrees C and 37 degrees C) and constant pH, and at the same temperature (22 degrees C) but various pHs (6.6, 7.0, and 7.4). Bleaching rate is slightly higher at 37 degree C than that at 22 degrees C. The basic form of the dye (lambda Em approximately 625 nm) has a slightly higher bleaching rate than the acidic form (lambda Em approximately 535 nm) in standard culture medium (pH 7.3) at either 22 degree C or 37 degrees C. The pHi in MDCK cells calculated from ratio images (535 nm/625 nm) was 7.19 +/- 0.03 (mean +/- SEM, n = 20). Calibration experiments show that the useful pH range of SNAFL-calcein appears to be between 6.2 and 7.8, as the dye is difficult to calibrate outside this pH range. PMID- 7790402 TI - Specific binding of leukemia inhibitory factor to murine myoblasts in culture. AB - Leukemia inhibitory factor (LIF) is a member of the cytokine family of growth factors. It has been shown to exert a variety of actions on a diverse range of cell types, including neuronal, bone, and hemopoietic cells (Hilton, 1992, Trends Biochem. Sci., 17:72-76). In many of these cell types, studies have indicated the presence of specific receptors for LIF (Godard et al., 1982, J. Biol. Chem., 267: 3214-3222; Hilton et al., Proc. Natl. Acad. Sci. USA, 85:5971-5975; Hilton and Nicola, 1992, J. Biol. Chem., 267:10238-10247.). The mechanism by which these receptors act is believed to involve tyrosine phosphorylation and the signal transducing receptor component gp130. We have previously shown that LIF is capable of inducing both human and murine myoblasts to proliferate in culture (Austin et al., 1992, J. Neurol. Sci., 112:185-191). We now report that LIF binds specifically to receptors on the surface of myoblasts, with an equilibrium dissociation constant of 400 pM and the number of receptors per cell varies with cell density. Binding competition studies showed that LIF binding to these receptor sites was not competed for by a number of other growth factors which stimulate myoblast proliferation including basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF alpha), insulin-like growth factor 1 (IGF 1), and interleukin-6 (IL-6). There was a time and concentration-dependent down regulation of receptor numbers following preincubation of myoblasts with LIF. The processing of these receptors subsequent to binding, involves as a first step, internalization and degradation by the myoblast. LIF appeared to stimulate myoblast proliferation rather than cell survival. PMID- 7790403 TI - Genetic factors influencing murine hematopoietic productivity in culture. AB - In order to study a previously described genetic difference manifested in stem cell kinetics of specific mouse strains, effects of this putative gene, stk, were measured on growth and expansion of stem and progenitor cell populations ex vivo. Bone marrow cells from each of two inbred mouse strains, C57BL/6J and DBA/2J, were placed into separate bioreactor cultures perfused continuously with growth medium containing erythropoietin (Epo), interleukin-3 (IL-3), granulocyte macrphage colony stimulating factor (GM-CSF), and Kit ligand as well as 5% CO2. Expansion of cell numbers reached 20-fold for DBA/2J and 10-fold for C57BL/6J marrow within about 1 week of culture. Significant production was also seen of colony-forming unit (CFU)-GM (up nine-fold from input levels) just prior to the cell production peak, and, importantly, moderate expansion of day 12 colony forming unit-spleen (CFU-S; two- to threefold) occurred as well, although CFU-S production peaked at a relatively short 4 days. CFU-S and CFU-GM levels declined rapidly in culture, either because of unfavorable growth conditions or terminal differentiation. Attempts to remove toxic metabolites by increasing the media perfusion rate resulted in a boost in cell expansion capability by DBA/2J marrow. In bioreactors in which stromal cells were established before marrow inoculation, there was greater expansion of CFU-S (especially by DBA/2J) and CFU-GM, although total cell yield appeared to be unaffected, perhaps because the maximum cell density had already been reached. The relative high potential for CFU-S expansion measured in DBA/2J marrow over that of C57BL/6J will be useful in following genetic contributions to bone marrow production capacity. PMID- 7790404 TI - Attenuation of stroke size in rats using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist in brain. AB - Adenoviruses have been proposed as potential vectors for gene therapy in the central nervous system, but there are no reports of their use in the treatment of a brain disease. Because central administration of interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain damage, we determined whether a recombinant adenovirus vector carrying the human IL-1ra cDNA (Ad.RSVIL-1ra) could be used to ameliorate brain injury in permanent focal ischemia. Groups of six rats received intraventricular injections of Ad.RSVIL-1ra or a control adenovirus containing the Escherichia coli beta-galactosidase gene (Ad.RSVlacZ). Histochemical staining for beta-galactosidase 5 days after virus injection indicated that transgene expression was confined primarily to the cells lining the ventricle. The concentrations of IL-1ra injected animals, achieving levels of 9.1 +/- 3.3 ng/g in brain and 23.7 +/- 22.5 ng/ml in CSF. In these animals, cerebral infarct volume resulting from 24 h of permanent middle cerebral artery occlusion was reduced 64%. These studies demonstrate that adenoviral vectors can be used to deliver genes that attenuate brain injury. PMID- 7790405 TI - Three-dimensional quantitative autoradiography by disparity analysis: theory and application to image averaging of local cerebral glucose utilization. AB - Traditional autoradiographic image analysis has been restricted to the two dimensional assessment of local cerebral glucose utilization (LCMRglc) or blood flow in individual brains. It is advantageous, however, to generate an entire three-dimensional (3D) data set and to develop the ability to map replicate images derived from multiple studies into the same 3D space, so as to generate average and standard deviation images for the entire series. We have developed a novel method, termed "disparity analysis," for the alignment and mapping of autoradiographic images. We present the theory of this method, which is based upon a linear affine model, to analyze point-to-point disparities in two images. The method is a direct one that estimates scaling, translation, and rotation parameters simultaneously. Disparity analysis is general and flexible and deals well with damaged or asymmetric sections. We applied this method to study LCMRglc in nine awake male Wistar rats by the [14C]2-deoxyglucose method. Brains were physically aligned in the anteroposterior axis and were sectioned subserially at 100-microns intervals. For each brain, coronal sections were aligned by disparity analysis. The nine brains were then registered in the z-axis with respect to a common coronal reference level (bregma + 0.7 mm). Eight of the nine brains were mapped into the remaining brain, which was designated the "template," and aggregate 3D data sets were generated of the mean and standard deviation for the entire series. The averaged images retained the major anatomic features apparent in individual brains but with some defocusing. Internal anatomic features of the averaged brain were smooth, continuous, and readily identifiable on sections through the 3D stack. The fidelity of the internal architecture of the averaged brain was compared with that of individual brains by analysis of line scans at four representative levels. Line scan comparisons between corresponding sections and their template showed a high degree of correlation, as did similar comparisons performed on entire sections. Fourier analysis of line scan data showed retention of low-frequency information with the expected attenuation of high-frequency components produced by averaging. Region-of-interest (ROI) analysis of the averaged brain yielded LCMRglc values virtually identical to those derived from measurements and subsequent averaging of data from individual brains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7790406 TI - Three-dimensional image analysis of brain glucose metabolism-blood flow uncoupling and its electrophysiological correlates in the acute ischemic penumbra following middle cerebral artery occlusion. AB - The relationship between local cerebral glucose utilization (LCMRglc) and local CBF (LCBF) is known to be disturbed in regions surrounding an acute focal ischemic lesion--areas that undergo repeated transient depolarizations. In this study, we evaluated the relationship between LCMRglc and LCBF in the acute focal ischemic penumbra to quantify metabolism-flow uncoupling, and we related these findings to local electrophysiological measurements. A novel strategy utilizing three-dimensional (3D) autoradiographic image averaging yielded group 3D reconstructions of LCBF, LCMRglc, and the CMR/CBF ratio. The distal right middle cerebral artery of Sprague-Dawley rats was occluded by laser-driven photothrombosis following administration of the photosensitizing dye rose bengal; this was coupled with permanent ipsilateral and 1-h contralateral common carotid artery occlusions. LCBF (n = 7) and LCMRglc (n = 7) were measured autoradiographically at 1.25 and 1.5-2 h postocclusion, respectively, in matched animal groups. Within the ischemic penumbra (defined as having LCBF of 20-40% of control or 0.23-0.47 ml g-1 min-1), LCMRglc showed a heterogeneous pattern with values ranging from near normal to markedly increased. The resulting CMRglc/CBF ratio in this zone was 234 +/- 100 mumol/100 ml (mean +/- SD), representing a severe degree of metabolism-flow dissociation when compared with the CMRglc/CBF ratio of 51.0 +/- 28.7 mumol/100 ml of the contralateral (normal) hemisphere. Metabolism-flow uncoupling was confined to the ipsilateral cortex and was most prominent at the anterior and posterior coronal poles of the ischemic lesion. In the frontoparietal penumbra, where marked uncoupling was observed, sustained deflections of the DC potential were recorded, which increased significantly in duration over the initial 65 min postocclusion. Both the heterogeneous pattern of LCMRglc and the widespread distribution of increased CMRglc/CBF ratio in the ischemic penumbra are thought to reflect the metabolic consequences of periinfarct depolarizations. Analysis of averaged 3D autoradiographic data sets provides a powerful means for assessing metabolism-flow uncoupling surrounding an ischemic focus. PMID- 7790407 TI - Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI. AB - Diffusion-weighted (DW) and gradient echo (GE) magnetic resonance images were acquired before and after occlusion of the middle cerebral artery (MCA) in the rat. Upon occlusion, an increase in DW imaging signal intensity was observed in a core area within the MCA territory, most likely reflecting cytotoxic edema. The signal from GE images, which is sensitive to changes in the absolute amount of deoxyhemoglobin, decreased following ischemia within a region that extended beyond the core area observed with DW imaging. This hypointensity is attributed to increases in blood volume and/or oxygen extraction fraction, which result from a decrease in perfusion pressure in the collaterally perfused area. The evolution of the GE imaging signal intensity from different regions was studied for 3.5 h following the occlusion. In the core area, the GE imaging signal returned towards baseline values after approximately 1-2 h, while it remained stable in the surrounding area. This feature may reflect a decrease in hematocrit due to microcirculatory defect and/or a decrease in the oxygen extraction fraction due to ongoing infarction of the tissue and may indicate that tissue recovery is severely compromised. The combined use of DW and GE imaging offers great promise for the noninvasive identification of specific pathological events with high spatial resolution. PMID- 7790408 TI - The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats. AB - In this study we evaluated the effect of the competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CGP 40116) on both early (2 days) and late (28 days) ischemic brain damage in a rodent model of focal cerebral ischemia by means of magnetic resonance imaging (MRI) and conventional histology. Immediately after occlusion of the left middle cerebral artery (MCA), rats received either CGP 40116 (20 mg/kg i.p.) or isotonic saline. Two MRI scans were performed in each animal 2 and 28 days after MCA occlusion. After the second scan, rats were perfusion fixed for histological evaluation. The volume of lesioned brain tissue as determined by MRI or histology was calculated from the damaged area in single sections and the distance between them. CGP 40116 reduced acute infarct volume as measured by MRI 2 days after MCA occlusion by 44% (p < 0.05, analysis of variance). After 28 days the lesion detected by MRI was still significantly smaller in the drug-treated animals. This finding was confirmed by the histological analysis showing a 64% reduction in the volume of brain atrophy in the CGP 40116 group (p < 0.05, analysis of variance). There was a good correlation between the MRI data and the results of the histological evaluation (r = 0.9). Our results indicate that (a) the competitive NMDA antagonist CGP 40116 permanently protects brain tissue from the consequences of cerebral ischemia in a rat model for human stroke and (b) early and late pathological changes can be accurately measured by MRI. PMID- 7790409 TI - A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia. AB - Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-D-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 +/- 15.8 microM (mean +/- SD) to 21.4 +/- 11.4 microM (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 +/- 5.8 to 19.9 +/- 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters. PMID- 7790410 TI - Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats. AB - Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke. PMID- 7790411 TI - Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. AB - The antioxidant dihydrolipoic acid has been shown to reduce hypoxic and excitotoxic neuronal damage in vitro. In the present study, we tested whether pretreatment with alpha-lipoic acid, which presumably allows endogenous formation of dihydrolipoic acid, can protect cultured neurons against injury caused by cyanide, glutamate, or iron ions, using the trypan blue exclusion method to determine neuronal damage. One hour of preincubation with dihydrolipoic acid (1 microM), but not with alpha-lipoic acid, reduced damage of neurons from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions. alpha-Lipoic acid (1 microM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pretreatment with alpha-lipoic acid for > 24 h enhanced this neuroprotective effect. Both the R- and the S-enantiomer of alpha-lipoic acid exerted a similar neuroprotective effect. Pretreatment with alpha-lipoic acid (1 microM) from the day of plating onward prevented the degeneration of chick embryo telencephalic neurons that had been exposed to Fe2+/Fe3+. alpha-Lipoic acid (1 microM) added to the culture medium the day of plating also reduced neuronal injury induced by 1 mM L-glutamate in rat hippocampal cultures, whereas 30 min of preincubation with alpha-lipoic acid failed to attenuate glutamate-induced neuronal damage. Our results indicate that neuroprotection by prolonged pretreatment with alpha-lipoic acid is probably due to the radical scavenger properties of endogenously formed dihydrolipoic acid. PMID- 7790413 TI - Changes in N-acetyl-aspartate content during focal and global brain ischemia of the rat. AB - N-Acetyl-aspartate (NAA) is almost exclusively localized in neurons in the mature brain and might be used as a neuronal marker. It has been reported that the NAA content in human brain is decreased in neurodegenerative diseases and in stroke. Since the NAA content can be determined by nuclear magnetic resonance techniques, it has potential as a diagnostic and prognostic marker. The objective of this study was to examine the change of NAA content and related substances following cerebral ischemia and compare the results to the damage of the tissue. We used rats to study the changes of NAA, N-acetyl-aspartyl-glutamate (NAAG), glutamate, and aspartate contents over a time course of 24 h in brain regions affected by either permanent middle cerebral artery occlusion (focal ischemia) or decapitation (global ischemia). The decreases of NAA and NAAG contents following global brain ischemia were linear over time but significant only after 4 and 2 h, respectively. After 24 h, the levels of NAA and NAAG were 24 and 44% of control values, respectively. The concentration of glutamate did not change, whereas the aspartate content increased at a rate comparable with the rate of decrease of NAA content. This is consistent with NAA being preferentially degraded by the enzyme amidohydrolase II in global ischemia. In focal ischemia, there was a rapid decline of NAA within the first 8 h of ischemia followed by a slower rate of reduction. The reductions of NAA and NAAG contents in focal ischemia were significant after 4 and 24 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790414 TI - Glial expression of the beta-amyloid precursor protein (APP) in global ischemia. AB - The beta-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postischemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1 and CA4 regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia. PMID- 7790412 TI - Cerebrovascular responses under controlled and monitored physiological conditions in the anesthetized mouse. AB - Control of physiological parameters such as respiration, blood pressure, and arterial blood gases has been difficult in the mouse due to the lack of technology required to monitor these parameters in small animals. Here we report that anesthetized and artificially ventilated mice can be maintained under physiological control for several hours with apparently normal cerebrovascular reactivity to hypercapnia and mechanical vibrissal stimulation. SV-129 mice were anesthetized with urethane (750 mg/kg i.p.) and alpha-chloralose (50 mg/kg i.p.), intubated, paralyzed, and artificially ventilated. Respiratory control was maintained within physiological range by reducing the inspiratory phase of the respiratory cycle to < 0.1 s and by adjusting end-tidal CO2 to give a PCO2 of 35 +/- 3 mm Hg. In these mice, mean arterial pressure (95 +/- 9 mm Hg), heart rate (545 +/- 78 beats/min), and arterial pH (7.27 +/- 0.10) could be maintained for several hours. Body temperature was kept at 36.5-37.5 degrees C. We observed stable regional CBF (rCBF) measurements (as determined by laser-Doppler flowmetry) when systemic arterial blood pressure was varied between 40 and 130 mm Hg. Hypercapnia led to a 38 +/- 15% (5% CO2) and 77 +/- 34% (10% CO2) increase in rCBF. Mechanical stimulation of contralateral vibrissae for 1 min increased rCBF by 14 +/- 4%. Changes in rCBF compare favorably with those observed previously in another rodent species, the Sprague-Dawley rat. After placement of a closed cranial window, cerebrovascular reactivity to hypercapnia and whisker stimulation was intact and well maintained during 2-h superfusion with artificial CSF. PMID- 7790415 TI - Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex. AB - Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+o never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain. PMID- 7790416 TI - Postischemic cerebral blood flow recovery in the female: effect of 17 beta estradiol. AB - Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17 beta-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17 beta-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 +/- 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 +/- 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 +/- 1 and 9 +/- 2 ml min-1 100 g-1, respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 +/- 27 and 183 +/- 27 ml min-1 100 g-1. However, EFEM experienced higher CBF during ischemia (e.g., 13 +/- 2 ml min 1 100 g-1) and less hyperemia (134 +/- 4 ml min-1 100 g-1 in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17 beta-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal. PMID- 7790417 TI - Poor hemodynamic and metabolic recovery after global incomplete cerebral ischemia associated with short-term diabetes in dogs. AB - We determined the effect of 4-5 weeks of diabetes on ATP recovery following global incomplete cerebral ischemia. 31P magnetic resonance spectra of ATP, intracellular pH (pHi), and CBF (radiolabeled microspheres) were measured in three groups of anesthetized dogs (n = 8/group): chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose of > 10 mM for 4-5 weeks); acute hyperglycemia (blood glucose of > 10 mM) during ischemia and reperfusion in nondiabetic dogs; and normoglycemic controls. Twenty minutes of incomplete ischemia was produced by ventricular fluid infusion to keep cerebral perfusion pressure (CPP) at 10 mm Hg during spontaneous variations in MABP. Intracranial pressure was increased initially to similar levels, resulting in a similar Cushing response among the groups. However, during the final 8 min of ischemia, MABP decreased to a greater extent in diabetic (86 +/- 42 mm Hg) than in hyperglycemic (162 +/- 30 mm Hg) and normoglycemic (135 +/- 54 mm Hg) groups and remained lower throughout 3 h of reperfusion. CPP was kept constant during ischemia, but was lower throughout reperfusion in diabetic dogs. During ischemia CBF was reduced similarly among groups: 5 +/- 3 ml.min-1 x 100 g-1 in hyperglycemic and normoglycemic and 4 +/- 3 ml.min-1 x 100 g-1 in diabetic dogs. During reperfusion early hyperemia was attenuated and delayed hypoperfusion was augmented (7 +/- 17 ml.min-1 x 100 g-1 by 180 min) as a result of low perfusion pressure in diabetics. However, medullary blood flow was similar among groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790418 TI - Regional congruence and divergence of glucose transporters (GLUT1) and capillaries in rat brains. AB - The association of glucose transporters (GLUT1) and brain capillaries was tested in different brain structures of rats by a direct comparison of the topologies of capillaries and GLUT1 in identical brain sections. Antibody staining of capillaries (fibronectin) and GLUT1 were made visible by fluorescence microscopy. The results showed differences between brain structures containing a tight and a leaky blood-brain barrier. All capillaries of brain structures with a tight blood brain barrier showed congruent staining of GLUT1 and capillary morphology. The circumventricular organs that are known to have leaky barrier capillaries were stained by fibronectin antibodies but not by GLUT1 antibodies. Ependymal cells showed moderate staining by GLUT1 antibodies both in areas with tight and leaky barriers. The subcommissural organ appeared to be unique showing neither capillary nor GLUT1 stain. It is concluded that glucose transporters (GLUT1) exist in all brain capillaries of blood-brain barrier structures, whereas they are absent in leaky barrier structures. Moderate amounts of glucose transporter (GLUT1) can also be detected in ependymal cells. PMID- 7790419 TI - Nicotine raises the influx of permeable solutes across the rat blood-brain barrier with little or no capillary recruitment. AB - Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (lCBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K1) and permeability-surface area (PS) products of [14C]antipyrine and [14C]-3-O-methyl-D-glucose (3OMG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of significantly increased PS products supports the capillary recruitment hypothesis. In 17 of 44 areas, nicotine treatment increased lCBF by 30-150%, K1 of antipyrine by 7-40%, K1 of 3OMG by 5-27%, PS product of antipyrine by 0.20% (mean 7%), and PS product of 3OMG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K1 of antipyrine were significant, whereas those in K1 of 3OMG and in PS for both antipyrine and 3OMG were not statistically significant. The lack of significant changes in PS products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capillaries were recruited and (b) blood flow within brain capillary beds rises by elevating linear velocity. The K1 results indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moderately permeable substances, and negligibly change those of solutes with extraction fractions of < 0.2, thereby preserving the barrier function of the blood-brain barrier. PMID- 7790420 TI - Enhanced cerebrovascular responsiveness to hypercapnia following depletion of central serotonergic terminals. AB - Serotonin-containing nerve fibres innervate cerebral blood vessels, but the source of this innervation and the physiological effects of perivascular serotonin release remain controversial. The purpose of the present study was to examine the effects of central serotonergic depletion upon the relationship between CBF and glucose utilization under both normo- and hypercapnic conditions. To induce the loss of serotonergic terminals, rats were injected twice daily for 4 consecutive days with 20 mg/kg of the specific serotonergic neurotoxin methylenedioxyamphetamine (MDA). Between 4 and 6 weeks later, local CBF and glucose utilization were measured using the fully quantitative [14C]iodoantipyrine and [14C]2-deoxyglucose autoradiographic techniques, respectively, and the efficacy of the lesioning protocol was assessed using [3H]paroxetine radioligand binding analysis. In all animals treated with MDA, there was a significant decrease in serotonin uptake sites throughout the brain, falling from 223 +/- 20 to 40 +/- 16 fmol/mg tissue in parietal cortex, for example, although the raphe nuclei themselves were unaffected (300 +/- 20 fmol/mg tissue in controls and 291 +/- 18 in MDA-treated rats). In normocapnic rats, the effects of MDA pretreatment upon blood flow and glucose use were slight and focally concentrated. However, when the animals were rendered hypercapnic, CBF was significantly higher in MDA-treated rats than in normal controls, for example, increasing from 356 +/- 22 ml 100 g-1 min-1 in frontal cortex of hypercapnic controls to 700 +/- 81 ml 100 g-1 min-1 in MDA-pretreated rats with similar levels of hypercapnia. In some brain areas of hypercapnic MDA-pretreated rats, blood flows were too high (> 800 ml 100 g-1 min-1) to be accurately quantified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790421 TI - Change in cerebral blood flow velocity with onset of EEG silence during inhalation anesthesia in humans: evidence of flow-metabolism coupling? AB - In eight subjects anesthetized with moderate to high doses of inhalation anesthetics (isoflurane or desflurane) during normocapnia, the onset of electrical silence in EEG was associated with a sudden reduction of blood flow velocity monitored from the middle cerebral artery. The magnitude of this reduction was 38 +/- 11% (mean +/- SD; range 24-44%). The change in EEG always preceded the change in flow velocity by 5-7 s. These observations suggest that some flow-metabolism coupling mechanism is preserved during inhalation anesthesia in humans. PMID- 7790422 TI - Possible utility of bilateral simultaneous TCD. PMID- 7790423 TI - Improved detection of Malassezia species in lipid-supplemented Peds Plus blood culture bottles. AB - The growth of Malassezia species in BACTEC Peds Plus blood culture bottles was optimized by using various lipid supplements. Palmitic acid (3%, wt/vol) was superior and overcame the inhibitory effect of blood in mock clinical specimens. Palmitic acid (3%) supplementation of Peds Plus bottles may improve recovery of Malassezia species in the BACTEC NR 660. PMID- 7790424 TI - Polyclonal Mycobacterium avium infections in patients with AIDS: variations in antimicrobial susceptibilities of different strains of M. avium isolated from the same patient. AB - Broth microdilution MICs were determined for pairs of strains isolated from five AIDS patients with polyclonal Mycobacterium avium infection. Four (80%) of the five patients were infected simultaneously with strains having different antimicrobial susceptibility patterns. These findings have implications for the interpretation of susceptibility data in M. avium prophylaxis and treatment trials. PMID- 7790426 TI - Evaluation of CMV-vue antigenemia assay for rapid detection of cytomegalovirus in mixed-leukocyte blood fractions. AB - The CMV-vue antigenemia assay was evaluated by using mixed-leukocyte (ML) blood fractions. Of 234 ML fractions studied, 32 (14%), 23 (10%), and 20 (8.5%) were positive in the CMV-vue assay and conventional and shell vial cultures, respectively. The CMV-vue assay was more sensitive than shell vial cultures for rapid detection of cytomegalovirus. ML fractions are appropriate specimens for the cytomegalovirus antigenemia assay. PMID- 7790425 TI - Absence of human papillomavirus sequences in ovarian pathologies. AB - The role of human papillomaviruses (HPVs) in ovarian epithelium (either normal or neoplastic) remains controversial. We have investigated by PCR the presence of HPV DNA in fresh tissue from ovarian neoplasms and in primary cell cultures established from either normal, benign or malignant ovarian surface epithelia. None of the fresh samples and primary ovarian cultures contained HPV DNA sequences. PMID- 7790427 TI - Evaluation of a modified nitrous acid extraction latex agglutination kit for grouping beta-hemolytic streptococci and enterococci. AB - The rapid and accurate identification of the Lancefield group of beta-hemolytic streptococci and enterococci is an important procedure in clinical laboratories. Latex agglutination techniques are more rapid and technically less demanding than traditional extraction-precipitation methods. Prolex (Pro-Lab Diagnostics, Richmond Hill, Ontario, Canada) is a latex agglutination kit which contains modified nitrous acid reagents to extract antigens and can be used to detect group D antigen in streptococci and enterococci, as well as group A, B, C, F, and G antigens. A total of 302 strains of streptococci and enterococci were tested with this kit. All streptococci of groups A (41 strains), B (39 strains), C (35 strains), D (3 strains), F (10 strains), and G (48 strains) were correctly grouped, as were 125 (97%) of 129 strains of enterococci. Prolex is a reliable method for grouping the beta-hemolytic streptococci and enterococci most frequently encountered in clinical laboratories. PMID- 7790428 TI - Difficulties encountered in identification of a nutritionally deficient streptococcus on the basis of its failure to revert to streptococcal morphology. AB - Difficulties were encountered in the recognition of a nutritionally deficient streptococcus which continued to display aberrant morphologic forms (especially bulbous swellings and filament formation) despite provision of growth factors. With isolates displaying diverse morphologic entities not characteristic of a given species, e.g., Streptobacillus moniliformis or Erysipelothrix rhusiopathiae, nutritionally deficient streptococci should be considered. PMID- 7790431 TI - Methods for predicting susceptibility of Streptococcus pneumoniae to cefixime. AB - Among 698 Streptococcus pneumoniae isolates, 475 were penicillin susceptible and > 99% of those were susceptible to 0.5 microgram of cefixime per ml; other pneumococci were tentatively assumed to be resistant to cefixime. A 1-microgram oxacillin disk was more reliable than a 5-micrograms cefixime disk for predicting susceptibility to cefixime. PMID- 7790429 TI - Evaluation of CPS ID2 medium for detection of urinary tract bacterial isolates in specimens from a rehabilitation center. AB - CPS ID2 medium (bioMerieux) enables the presumptive identification of Escherichia coli and enterococci as well as the detection of indologenous or nonindologenous Proteeae and bacteria belonging to the Klebsiella, Enterobacter, and Serratia group with a specificity ranging from 98 to 100%. When the cultures were polymicrobial, the sensitivity varied from 70 to 97%, and the sensitivity varied from 97 to 100% when they were monomicrobial. PMID- 7790430 TI - Factors affecting growth and susceptibility testing of Helicobacter pylori in liquid media. AB - In order to increase the database for in vitro growth and/or susceptibility testing in liquid media, we evaluated the growth of Helicobacter pylori in broth media containing 5% sheep blood. We also compared the effect of bismuth on the growth of H. pylori in broth media containing 10% fetal calf serum with the effect on growth in media containing 0.5% starch. In contrast to the result seen with agar, we found that sheep blood, whether whole or laked, inhibited the growth of H. pylori in broth media. In addition, we found that bismuth inhibited growth in media with starch but that this inhibition was negated in media with serum. PMID- 7790432 TI - Diagnosis of American trypanosomiasis (Chagas' disease) by the new complement fixation test. AB - A new immunodiagnostic method of complement fixation was used for serodiagnosis of American trypanosomiasis; 92% sensitivity and 99% specificity were obtained, for an overall accuracy of 97%. This test can be used in field studies, obviating the use of most laboratory equipment and imported reagents; places where economic limitations hinder the use of other immunodiagnostic procedures; and in association with other tests for confirmation of the diagnosis. PMID- 7790433 TI - Alterations in sample preparation increase sensitivity of PCR assay for diagnosis of chancroid. AB - A PCR assay for the detection of Haemophilus ducreyi in clinical specimens taken from genital ulcers was developed. Although H. ducreyi, when present in such specimens, could be detected by PCR, the sensitivity of the assay was reduced by the presence of Taq polymerase inhibitors in the specimen. The sensitivity of the PCR assay was improved by the use of detergents in preparing nuclei acids from clinical specimens and by the inclusion of a dialysis step prior to amplification. In addition, sodium phosphate included in the transport medium was found to be an inhibitor of the Taq polymerase. PMID- 7790435 TI - Mycobacterium asiaticum as the probable causative agent in a case of olecranon bursitis. AB - Mycobacterium asiaticum was isolated from fluid aspirated from an olecranon bursa that had become inflamed following a superficial injury. Other possible causes of the inflammation were excluded. No specific antimycobacterial therapy was given. The infection responded to drainage, regular dressing, and immobilization. Our experience suggests that M. asiaticum is a potential cause of infection of the joints and surrounding tissues. PMID- 7790434 TI - Differentiation of Neisseria gonorrhoeae isolates requiring proline, citrulline, and uracil by plasmid content, serotyping, and pulsed-field gel electrophoresis. AB - A combination of DNA macrorestriction analysis using pulsed-field gel electrophoresis and a serotyping method using three panels of monoclonal antibody was used to discriminate 43 epidemiologically unrelated Neisseria gonorrhoeae isolates requiring proline, citrulline, and uracil (PCU-) into 35 groups. This indicates that PCU- isolates of N. gonorrhoeae are not clonal. PMID- 7790436 TI - More about cefuroxime screening test for pneumococci. PMID- 7790437 TI - Detection of Salmonella species in fecal samples by immunomagnetic separation and PCR. PMID- 7790438 TI - Detection of vancomycin resistance in enterococci by the Alamar MIC system. AB - The ability of the Alamar microdilution MIC system to detect vancomycin resistance in enterococci was evaluated by comparing the results with an agar dilution screen method. Of 100 strains tested, 41 were resistant and 47 were susceptible by both tests. Five strains were intermediate and one was resistant by the Alamar MIC system but susceptible by the agar screen. Three strains each were susceptible or intermediate by the Alamar MIC system but resistant by the agar screen. The predictive values for the Alamar MIC system were 94% (susceptible) and 88% (combined intermediate and resistant). The Alamar MIC system does not appear to have sufficient accuracy for the detection or confirmation of vancomycin resistance in enterococci. PMID- 7790439 TI - Stability of karyotype in serial isolates of Candida albicans from neutropenic patients. AB - Serial isolates of Candida albicans were obtained from 20 patients with leukemia over periods of up to 8 months. The fingerprinting of these isolates by interrepeat PCR and random amplified polymorphic DNA PCR has been described previously (A. van Belkum, W. Melchers, B. E. de Pauw, S. Scherer, W. Quint, and J. F. Meis, J. Infect. Dis. 169:1062-1070, 1994). Contour-clamped homogeneous electric field gel electrophoresis was used to examine the chromosomes of these isolates. When changes in the karyotype were seen in a series of isolates, additional interrepeat PCR and Southern blotting with a repeat DNA sequence from the 27A family were performed. These two genotyping tools were used to determine if karyotypic changes seen in a series of isolates were due to chromosome rearrangements in a single strain or due to colonization with more than one strain. It was determined that changes in karyotype in a series of strains indicated infection by a new strain. PMID- 7790441 TI - Evaluation of five new plating media for isolation of Salmonella species. AB - A three-phase study was conducted to compare Hektoen enteric agar (HE), Rambach agar (Ra), SM-ID medium (SM), xylose-lysine-Tergitol 4 agar (XLT4), novobiocin brilliant green-glycerol-lactose agar (NBGL), and modified semisolid Rappaport Vassiliadis medium (MSRV) for the recovery of nontyphoid salmonellae from stool specimens. After evaluation of the first two phases, which resulted in the elimination of Ra, SM, and NBGL, 593 consecutive stool samples were investigated by plating them directly and after tetrathionate enrichment at 37 degrees C on HE, XLT4, and MSRV. A total of 82 Salmonella-positive stool specimens were detected (positivity rate, 13.8%). Sensitivities for direct plating and after tetrathionate enrichment were 32.9 and 86.6%, respectively, for XLT4, 63.4 and 100.0%, respectively, for MSRV, and 34.1 and 79.3%, respectively, for HE. Specificities (percentage of morphologically suspicious colonies that were indeed salmonellae) were 100.0 and 99.8%, respectively, for XLT4, 99.0 and 98.8%, respectively, for MSRV, and 67.9 and 75.0%, respectively, for HE. The use of MSRV instead of HE increased the isolation rate of salmonellae by 26.2% (65 versus 82 strains isolated from HE and MSRV, respectively). We conclude that MSRV is the most sensitive medium tested and is a very specific medium for the isolation of nontyphoid salmonellae from stool specimens. However, its semisolid nature is a disadvantage and requires careful handling in the laboratory, especially when salmonellae are present. XLT4 had a sensitivity comparable to that of HE and a nearly 100% specificity and can be regarded as an alternative for the isolation of nontyphoid salmonellae from stool samples. PMID- 7790442 TI - Comparison of commercial enzyme immunoassay kits with plaque reduction neutralization test for detection of measles virus antibody. AB - Four commercially available enzyme immunoassay (EIA) kits were evaluated in comparison with the plaque reduction neutralization (PRN) test for detection of measles virus antibody. The EIA kits, Enzygnost (Behring), Diamedix, Vidas (bioMerieux Vitek), and Measlestat (Biowhittaker), were assessed with two PRN cutoff titers: a PRN titer of 8, the lowest detectable antibody level by the PRN test under the test conditions, and a titer of 120, which has been shown to be the minimum protective antibody titer. At a PRN cutoff titer of 8, the sensitivity was 88.2, 91.1, 74.6, and 69.8% for Behring, Diamedix, Vidas, and Biowhittaker EIA tests, respectively, with negative predictive values ranging from 22.7 to 45.5%. The specificity was 93.8% for Diamedix and 100% for the rest. At a PRN cutoff titer of 120, the sensitivity and specificity, respectively, were 100 and 90.7% (Behring), 98.2 and 58.8% (Diamedix), 90.6 and 94.5% (Vidas), and 85.7 and 96.4% (Biowhittaker). At this PRN cutoff titer, the negative predictive values of all EIA tests improved considerably, ranging from 70.7 to 100%. The EIA results showed an excellent association with PRN results when the PRN titers of the test samples were either < 8 or > 1,052. Discrepancies occurred especially when testing samples having PRN titers in the range of 8 to 120, indicating lack of sensitivity of the EIA tests in detecting measles virus antibody at low levels. Maternally derived measles virus antibody at this level has been shown to interfere with measles vaccine response in children and hence has implications from the standpoint of measles immunization. The ready availability, ease of operation, and rapid turnaround time are strong plus points of the EIA kits, and they could be useful in a clinical laboratory setting for routine application, but they may have limited use in vaccine-related studies and seroepidemiological surveys. PMID- 7790440 TI - Typing of human astroviruses from clinical isolates by enzyme immunoassay and nucleotide sequencing. AB - A typing enzyme immunoassay (TYPE-EIA) was used to determine the antigenic types of 64 astrovirus-positive specimens from nine collections from seven countries. Six of the seven known astrovirus types were detected in the collections, with HAstV-1 predominating in all collections for one from the United Kingdom. Selected specimens were analyzed further by reverse transcriptase PCR and nucleotide sequencing of 348 bp within the capsid protein precursor region of the genome. The phylogenetic groupings (genotypes) determined from the sequences were entirely consistent with the antigenic groupings (serotypes) of isolates obtained by using the TYPE-EIA. The genetic variation within genotypes was small compared with the variation between genotypes, allowing unambiguous categorization of all specimens. Although some strains from widely separated geographic areas had identical sequences, in general, within a region most strains of the same type were identical. The TYPE-EIA may help further our understanding of the epidemiology of astrovirus and the possible role of serotype-specific immunity, while further knowledge of sequences could facilitate the development of simpler molecular methods of typing astrovirus strains. PMID- 7790443 TI - Coagulase-negative staphylococci in multiple blood cultures: strain relatedness and determinants of same-strain bacteremia. AB - The frequency of strain relatedness was determined among randomly selected patients with coagulase-negative staphylococcal infections as determined in multiple blood cultures by plasmid typing, determination of species, and antibiotyping. Strain relatedness was demonstrated in 21 of 47 episodes of bacteremia (44.7%) among 34 patients, with a similar percentage among patients with two or one positive blood culture in 24 h (14 of 30 [46.7%] versus 7 of 17 [41.2%], respectively). Same-strain bacteremia was more frequent in cases of infection among patients with a corresponding fever (15 of 21 [71.4%]), among patients infected with organisms from an identifiable source (7 of 9 [77.8%]) and with non-Staphylococcus epidermidis species (9 of 11 [81.8%]), and among patients with nosocomially acquired infections (18 of 36 [50%]). Comparing episodes with or without strain relatedness, no difference was noted in the time to growth (2.1 +/- 1.4 versus 1.9 +/- 0.9 days, respectively), in bacterial growth in two culture bottles (5 of 14 [35.7%] versus 8 of 24 [33.3%], respectively), and in the presence of additional negative blood cultures (9 of 21 [42.9%] versus 11 of 26 [42.3%], respectively). The antibiotypes of all related strains and 7 of 44 (15.9%) unrelated pairs were identical. These findings demonstrate that coagulase negative staphylococci from multiple blood cultures are frequently unrelated, suggesting a high prevalence of contamination. In the absence of precise measures for demonstrating strain relatedness, the combination of a clinical assessment with antibiotype determination appears to be a suitable alternative. PMID- 7790444 TI - Detection of Borna disease virus RNA in formalin-fixed, paraffin-embedded brain tissues by nested PCR. AB - A method for detecting Borna disease virus (BDV) RNA in formalin-fixed, paraffin embedded brain tissue sections was established. By digestion with proteinase K and subsequent extraction with guanidinium thiocyanate, phenol, and chloroform, we were able to efficiently release RNA from the fixed tissues. By reverse transcription of the RNA and nested PCR a 212-bp product was generated, as expected. PMID- 7790445 TI - Detection of Rickettsia japonica in Haemaphysalis longicornis ticks by restriction fragment length polymorphism of PCR product. AB - PCR was applied to the detection of Rickettsia japonica, the causative agent of Oriental spotted fever (OSF), in ticks collected at two sites of the Muroto area on Shikoku Island, a major area in Japan where OSF is endemic. Primer pair Rr190.70p and Rr190.602n of the R. rickettsii 190-kDa antigen gene sequence of Regnery and others (R.L. Regnery, C.L. Spruill, and B.D. Plikaytis, J. Bacteriol. 173:1576-1589, 1991) primed the DNA extracted from Haemaphysalis longicornis ticks but not those extracted from Haemaphysalis formosensis, Haemaphysalis flava, Haemaphysalis hystricis, or Amblyomma testudinarium ticks. Digestion of the amplification product with the restriction endonucleases PstI and AluI produced the restriction fragment length polymorphism pattern specific to R. japonica. The HindIII and MspI digests gave restriction fragment length polymorphism patterns identical to those of the PCR product from R. japonica DNA. Hemolymph preparations of H. longicornis ticks were demonstrated to contain rod shaped organisms that were detected by immunofluorescence with the monoclonal antibody specific to R. japonica species. The primer pair did not amplify the DNA of a laboratory colony of H. longicornis ticks originally collected at an area where OSF is not endemic. Our results provided evidence that H. longicornis ticks might be an arthropod reservoir for R. japonica and a vector of OSF. PMID- 7790447 TI - Detection and identification of aquatic birnaviruses by PCR assay. AB - A reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for the detection and identification of aquatic birnaviruses. The four sets of primers (PrA, PrB, PrC, and PrD) that we used are specific for regions of cDNA coded by genome segment A of aquatic birnaviruses. PrA identifies a large fragment (1,180 bp) within the pVP2-coding region, and PrB identifies a 524-bp fragment within the sequence amplified by PrA. Primer set PrC frames a genome fragment (339 bp) within the NS-VP3-coding region, and PrD identifies a 174-bp sequence within the fragment identified by PrC. PrB and PrD amplified cDNAs from all nine recognized serotypes of aquatic birnavirus serogroup A as well as the N1 isolate that may represent a 10th serotype. These results indicate that these three primer sequences are highly conserved and can be used in PCR assays for group identification of these viruses. PrA routinely produced amplification products from eight serotypes but exhibited variable results with one serotype, and primer PrC identified 6 of the 11 virus isolates tested. The qualitative sensitivity of the RT-PCR assay was evaluated by comparison of the results with those of cell culture isolation assays. With the exception of one sample, the RT PCR assay with primer PrD was as accurate as cell culture isolation for detecting virus in kidney and spleen tissues from naturally infected, asymptomatic carrier fish. These results indicate that the RT-PCR assay can be a rapid and reliable substitute for cell culture methods for the detection of aquatic birnaviruses. PMID- 7790449 TI - Evaluation of a new identification system, Crystal Enteric/Non-Fermenter, for gram-negative bacilli. AB - A total of 505 fermentative and 201 nonfermentative gram-negative bacilli, identified by conventional methods, were tested by the Crystal Enteric/Non Fermenter ID kit and by the API 20E or API 20NE identification system. The overall correct results for fermenters were 92.9% by the Crystal kit and 89.1% by the API 20E system. The false identifications (genus and species incorrect) accounted for 3.1 and 7.1% for the Crystal and API systems, respectively. For nonfermenters, figures for correct identifications by the two systems were comparable (Crystal, 75.9%; API 20NE, 75.3%) while the API 20NE system gave twice as many incorrect results (13.8%) as Crystal (6.3%); however, Crystal failed to precisely identify several species included in a "miscellaneous" group. The Crystal Enteric/Non-Fermenter system is an easy-to-use kit which compares favorably with other commercial systems. PMID- 7790446 TI - Collagenases and the serine proteinases elastase and cathepsin G in steroid induced Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia (PCP) is characterized by the formation of leaky alveoli and a foamy alveolar exudate. To induce PCP, male Wistar rats were immunosuppressed by oral dexamethasone treatment for 12 weeks, during which time all rats developed PCP. Bronchoalveolar lavage fluid (BALF) was analyzed at that time and at 1, 2, and 4 weeks after the cessation of dexamethasone treatment, during which time the rats were recovering from PCP and immunosuppression (and was compared with the BALF obtained from healthy control rats), for type IV collagenase, elastase, cathepsin G, and collagenase activities. Scores for 72-kDa (matrix metalloproteinase type [MMP-2]) and 92-kDa (MMP-9) type IV collagenase gelatinase activities correlated with those for BALF macrophages (r = 0.58; P < 0.001) and neutrophils (r = 0.66; P < 0.001), respectively, suggesting that they may, in part, be derived from these cells. However, MMP-2 was constitutively expressed and may play a role in normal tissue remodeling. MMP-9 activity was highest in the group with PCP (1.8 +/- 0.37; P > 0.05), with a gradual decline (1.0 +/- 0.48 by week 4; P > 0.05) toward normal (0.67 +/- 0.42) during recovery, which suggests a role for it in tissue-destructive inflammatory events. In rats with PCP the endogenously active collagenase was present at high levels compared with those in healthy controls (2.6 +/- 0.69 versus 0.17 +/- 0.17, respectively; P < 0.01), but they returned to normal by week 4 of recovery (0.42 +/- 0.30; P > 0.05). Collagenase activity showed a correlation with cyst number (r = 0.57; P < 0.001). The BALF of rats with PCP also contained the serine proteinases, which may act as pro-MMP activators. Ultramorphology disclosed increased pinocytotic activities, subepithelial bleb formation, and degeneration and denudation of the basal lamina. These findings suggest that the increased activities of collagenases in BALF caused by the host response against P. carinii might contribute to leaky alveoli. PMID- 7790450 TI - Anti-idiotypic antibody as potential serodiagnostic reagent for detection of bluetongue virus infection. AB - Polyclonal anti-idiotypic antibodies (anti-Ids) were generated by the sequential immunization of rabbits with three mouse monoclonal antibodies (MAb1s) specific for a major bluetongue virus (BTV) protein, VP7. The anti-Ids, designated RAb2s, recognized idiotopes which were located within or near the antigen-combining sites of the MAb1s and were associated with both heavy and light chains of MAb1s. RAb2s inhibited the MAb1s from binding to BTV antigens, and their interaction with MAb1s was inhibited by BTV antigens. By recognizing the common idiotopes, RAb2s detected anti-BTV antibodies from bovine antisera; their interaction was also partially inhibited by BTV antigens. These results indicated that RAb2s recognized the common idiotopes on anti-VP7 antibodies obtained from mice and cattle and that at least a portion of RAb2s were internal-image anti-Ids that functionally mimicked VP7. RAb2s may be used to substitute for the tissue culture derived viral antigen in currently used serological assays for the detection of antibodies to BTV. PMID- 7790451 TI - Identification of Campylobacter jejuni on the basis of a species-specific gene that encodes a membrane protein. AB - To facilitate discrimination between the closely related enteropathogens Campylobacter jejuni and C. coli, unique differences in antigenic surface structure were examined. A genomic library of C. jejuni 81116 was constructed in plasmid pBluescriptIISK- and expressed in Escherichia coli K-12. Rabbit hyperimmune serum raised against C. jejuni ATCC 29428 recognized a clone expressing a C. jejuni 24-kDa membrane-associated protein. Antiserum raised against sonicated recombinant E. coli expressing the 24-kDa protein reacted with C. jejuni, whereas C. coli did not react specifically. Determination of the nucleotide sequence of the DNA insert of this recombinant plasmid revealed an open reading frame encoding 214 amino acids; the gene was designated mapA; and its gene product was designated MAPA. The 18 N-terminal amino acid residues constitute a signal sequence characteristic of prokaryotic membrane lipoproteins. In a dot blot hybridization assay with a mapA probe, 120 clinical isolates of C. jejuni were unequivocally discriminated from 126 other campylobacters, including 34 C. coli isolates. A PCR test based on the mapA sequence was developed for identification of C. jejuni. A PCR product was obtained with all of the clinical isolates of C. jejuni tested from human, dog, cat, bovine calf, and chicken sources. Recombinant MAPA with an added C-terminal six-histidine tail was affinity purified and used to immunize rabbits. The rabbit anti-MAPA serum specifically recognized the protein in whole cells of C. jejuni on Western blots (immunoblots). The MAPA protein was present in all of the C. jejuni strains tested and was absent in C. coli and related campylobacters. PMID- 7790452 TI - Evaluation and comparison of different blood culture techniques for bacteriological isolation of Salmonella typhi and Brucella abortus. AB - An experimental study was carried out to evaluate and compare various noncommercial methods of blood culture for the isolation of Salmonella typhi and Brucella abortus from fresh human blood samples that had been artificially inoculated with 1 to 50 microorganisms per ml of blood. The methods compared included the Ruiz-Castaneda blood culture, broth blood culture, leukocyte lysis and direct plating on agar (WBL-P), leukocyte lysis and filtration, Ficoll Hypaque centrifugation and filtration, Ficoll-Hypaque centrifugation, and Ficoll Hypaque centrifugation and leukocyte lysis methods. Results with the WBL-P technique showed that S. typhi was isolated in 18 h, and its recovery rate was 36.6% (calculated from the number of CFU recovered per milliliter versus the number inoculated). B. abortus was isolated in 48 h by the same technique, and its recovery rate was 48.8%. The isolation times for the other blood culture techniques were between 36 and 44 h for S. typhi and 66 h for B. abortus. The techniques which relied on filtering systems for the recovery of S. typhi and B. abortus performed poorly. The WBL-P technique for the isolation of S. typhi and B. abortus is faster than the other methods tested. PMID- 7790453 TI - Evaluation of risk and diagnostic value of quantitative assays for anti Toxoplasma gondii immunoglobulin A (IgA), IgE, and IgM and analytical study of specific IgG in immunodeficient patients. AB - To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detected by ICT only in 12% of patients and aided the diagnosis in 1 of 71 patients. IC tests for specific IgA and IgE alone and combined with ELIFA were positive in 39 and 46% of patients who developed clinical toxoplasmosis, respectively. In a serial study of 16 patients in whom at least one of these three tests was positive, a significant immunological signal sometimes preceded clinical onset by 1, 6, and even 17 months. Similarly, in a group of human immunodeficiency virus-infected patients with evidence of previous exposure to T. gondii but no clinical manifestations, IgA, IgE, and IgA and/or IgE antibodies were detected in only 11, 4, and 12% of patients, respectively. These two situations point to peripheral T. gondii reactivation. IgA and IgE emerged as interesting markers of the risk of toxoplasmosis in immunodepressed patients. They may also provide valuable assistance in the diagnosis of toxoplasmosis, especially because tests for specific IgM are disappointing. However, at least one in two patients with toxoplasmosis showed no detectable immunological reaction, suggesting that this polyisotypic approach should be combined with other noninvasive methods such as gene amplification. PMID- 7790448 TI - Differentiation of strains in Mycobacterium tuberculosis complex by DNA sequence polymorphisms, including rapid identification of M. bovis BCG. AB - The Mycobacterium tuberculosis complex includes M. tuberculosis, M. bovis, M. microti, and M. africanum. Seven strains of the M. tuberculosis complex were sequenced in a region of about 300 bp which contains multiple 15-bp tandem repeats and which is part of a 1,551-bp open reading frame. Four distinct sequences were obtained, each defining a sequevar. A sequevar includes the strain or strains with a given sequence. The type strain M. tuberculosis TMC 102 (H37Rv) was designated sequevar MED-G. When compared to MED-G, sequevar LONG had an insertion of one 15-bp tandem repeat and sequevar SHORT had a deletion of one tandem repeat. Sequevar MED-C had a G-->C substitution, coding for the conservative change Ser-->Thr. BanI cuts only sequevar MED-C at the site of the substitution. PCR-restriction enzyme analysis was used to determine the sequevars of 92 M. tuberculosis complex strains. All 23 M. bovis BCG strains belonged to sequevar MED-C. The M. africanum type strain was sequevar SHORT. The remaining 68 strains of M. tuberculosis, M. bovis (not BCG), and M. microti were sequevars LONG (3 strains) or MED-G (65 strains). PCR-restriction enzyme analysis was applied to reference strains and clinical isolates with a worldwide distribution. This method provides rapid, sensitive, and specific identification of the important vaccine strain M. bovis BCG. PMID- 7790454 TI - Evaluation of three disk tests for identification of enterococci, leuconostocs, and pediococci. AB - Simple rapid tests for presumptive identification of catalase-negative non-beta hemolytic cocci (i.e., enterococci, leuconostocs, and pediococci) have not previously been available. Seven hundred thirty-four strains of aerobic and facultatively anaerobic, catalase-negative, non-beta-hemolytic gram-positive cocci were tested for susceptibility to vancomycin (Vans) by a screening procedure and production of leucine aminopeptidase (LAPase) and pyrrolidonylarylamidase (PYRase) in disk tests. Three unique patterns of activity in response to the three disks (30 micrograms of vancomycin, PYRase, and LAPase) can be used to presumptively identify the vancomycin-resistant (Vanr) enterococci (Vanr and PYRase and LAPase positive), leuconostocs (Vanr and PYRase and LAPase negative), and pediococci (Vanr, PYRase negative, and LAPase positive). The results indicate that, together with Gram stain characteristics and the catalase test, the vancomycin, LAPase, and PYRase disk tests can be used to presumptively identify Vanr strains of enterococci as well as Leuconostoc and Pediococcus strains from human infections. PMID- 7790455 TI - Identification and ribotypes of Staphylococcus caprae isolates isolated as human pathogens and from goat milk. AB - We report five cases of human infection with Staphylococcus caprae. Two were community acquired (one case each of endocarditis and urinary tract infection); the other three were acquired in a hospital (two cases of bacteremia associated with intravenous access and one case of urinary tract infection). Analysis of human isolates and goat isolates from eight herds showed that they could be misidentified by some commercial identification systems but were clearly identified as S. caprae by ribotyping, according to their species-specific ribotype. Phylogenetic methods applied to the ribotypes did not reveal two distinct lineages corresponding to the goat and human origins of the isolates, although human ribotypes were clearly distinguishable by the presence of a core of four specific bands. The latter observation may reflect some degree of evolutionary change within the species between human and goat isolates. PMID- 7790456 TI - Detection of Chlamydia trachomatis in urine specimens from women by ligase chain reaction. AB - The performance of a plasmid-based ligase chain reaction (LCR) with urine specimens was compared with those of cell culture of cervical swabs and enzyme immunoassay with urine specimens for the detection of Chlamydia trachomatis infection in women who had attended a family planning clinic. The prevalence of chlamydial infection determined by LCR was 3.1%. Discrepant results among the three assays were resolved by testing urine by a second LCR assay based on the C. trachomatis chromosomal gene encoding the major outer membrane protein. Sensitivity, specificity, and positive and negative predictive values for the cell cultures were 56.3, 100, 100, and 98.4%, respectively, whereas those for the enzyme immunoassay were 18.8, 100, 100, and 97.1%, respectively, and those for LCR were 87.5, 100, 100, and 99.5%, respectively. LCR thus provides a highly sensitive and specific noninvasive screening method for detecting genital chlamydial infections in women. PMID- 7790457 TI - Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes. AB - In recent years, general primer-mediated PCR assays have been developed to detect a broad spectrum of human papillomavirus (HPV) genotypes. In this study, a procedure enabling a simple group-specific differentiation of high-risk (HPV-16, 18, -31, -33, -35, -39, -45, -51, -52, -54, -56, and -58) and low risk (HPV-6, 11, -34, -40, -42, -43, and 44) HPVs following an HPV general primer-mediated (GP5+/GP6+) PCR is presented. By computer-assisted sequence analysis, oligonucleotides (30-mers) specific for 19 different HPV genotypes were selected from the internal part of the 150-bp GP5+/GP6(+)-amplified region. These oligo probes were tested for specificity in a Southern blot analysis of PCR products derived from the same panel of HPV types. No cross-hybridizations were found. The sensitivities of the oligo probes varied from the femtogram level for the well amplified HPV types like HPV-16 and -18 to the picogram level for the less-well amplified HPV types like HPV-39 and -51. These sensitivities were reached when the oligo probes were applied both individually and in a cocktail. On the basis of these results, two cocktail oligo probes that enabled a specific and sensitive differentiation between low- and high-risk HPV types were composed. PMID- 7790458 TI - Simple determination of human immunodeficiency virus type 1 syncytium-inducing V3 genotype by PCR. AB - Human immunodeficiency virus type 1 (HIV-1) phenotype variability plays an important role in the pathogenesis of AIDS. The presence of syncytium-inducing (SI) HIV-1 isolates in infected individuals is associated with a rapid decline of CD4+ T cells, rapid disease progression, and reduced survival time after AIDS diagnosis. The strong association between the SI capacity of HIV-1 and the presence of positively charged amino acid residues at positions 306 and/or 320 in the third variable domain (V3) of gp120 could here be confirmed in 97% of 402 primary HIV-1 isolates, indicating that the V3 genotype may be useful for prediction of the viral phenotype. The V3 DNA sequences revealed a remarkably limited codon usage for the amino acid residues that are responsible for virus phenotype. On the basis of this limited SI-specific DNA sequence variation, four SI-specific oligonucleotides were designed for selective amplification of V3 from SI but not non-SI HIV-1 isolates. This PCR analysis allowed the prediction of the biological phenotype of HIV-1 isolates on the basis of the V3 genotype and may prove to be useful for monitoring SI capacity of HIV-1 isolates in infected individuals. PMID- 7790459 TI - Epidemiological typing of Stenotrophomonas (Xanthomonas) maltophilia by PCR. AB - We used two PCR methods for epidemiological typing of Stenotrophomonas (Xanthomonas) maltophilia with either arbitrary primers (random amplified polymorphic DNA) or enterobacterial repetitive intergenic consensus sequences as primers (ERIC-PCR). The analysis was performed with 38 isolates of S. maltophilia, comprising 9 nosocomial isolates from a burn unit, 20 other clinical isolates epidemiologically unrelated, and 9 isolates from one cystic fibrosis patient. Both methods indicated that all of the nosocomial episodes were independent. In contrast, the nine isolates from the cystic fibrosis patient were assigned to very closely related profiles, especially by ERIC-PCR. We conclude that random amplified polymorphic DNA and ERIC-PCR have comparable reproducible and discriminatory powers for epidemiological typing of S. maltophilia, but ERIC PCR profiles can be more easily evaluated. PMID- 7790460 TI - Use of a colorimetric system for yeast susceptibility testing. AB - We examined the reliability and accuracy of a colorimetric assay using Alamar Blue reagent in the performance of susceptibility tests for Candida albicans. We compared the broth macrodilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) with a macrodilution method modified with the Alamar reagent and a microdilution method modified with the Alamar reagent. The MICs of fluconazole and itraconazole for 97 isolates of C. albicans and 3 control isolates were tested. For fluconazole, the Alamar-modified broth macrodilution method yielded 94% (91 of 97) concordance within 2 dilutions compared with the NCCLS method, while the microdilution method yielded 95% (92 of 97) concordance. With Alamar-modified methods for itraconazole, broth macrodilution yielded 97% (94 of 97) concordance within 2 dilutions. MICs obtained by the microdilution method, although tightly nested, were shifted to a higher value when compared with those obtained by the NCCLS method; there was only 77% (75 of 97) concordance within 2 dilutions but 97% concordance (94 of 97) within 3 dilutions. Tests by all methods with quality control strains showed excellent reproducibilities. For fluconazole, the methods modified with the Alamar reagent yielded clear endpoints and excellent correlation for the broth macrodilution and microdilution methods. For itraconazole, the methods modified with the Alamar reagent yielded clear endpoints and were reproducible, but higher MICs were obtained by the microdilution methods compared with those obtained by the NCCLS methods. PMID- 7790462 TI - Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa. AB - Secretion of Pseudomonas aeruginosa elastase, exotoxin A, and alkaline protease in sputum during bronchopulmonary exacerbations was examined in 18 cystic fibrosis patients chronically infected with this microorganism. The patients were studied during one or several exacerbation periods necessitating hospitalizations of 12 to 20 days. In all cases, P. aeruginosa was present in bronchial secretions at admission and was not eradicated after treatment. The P. aeruginosa density decreased significantly after antibiotic therapy but remained greater than 10(6) CFU/g of sputum in most cases. Significant amounts of P. aeruginosa exoproteins were measured in total homogenized bronchial secretions by immunoenzymatic assays. The detection of higher levels of exoproteins at admission, the significant decrease after treatment, and the absence of exoproteins during intercrisis phases constituted arguments for a renewal of virulence of P. aeruginosa during exacerbations. Nevertheless, the concomitant changes in bacteria load and the triggering of the inflammatory process and immune complex formation could also contribute to pulmonary exacerbations. PMID- 7790461 TI - Long-term colonization with single and multiple strains of Helicobacter pylori assessed by DNA fingerprinting. AB - The gastric pathogen Helicobacter pylori establishes long-term chronic infections that can lead to gastritis, peptic ulcers, and cancer. The species is so diverse that distinctly different strains are generally recovered from each patient. To better understand the dynamics of long-term carriage, we characterized H. pylori isolates from initial and follow-up biopsy specimens from a patient population at high risk of H. pylori infection and gastric cancer. Eighty-five isolates were obtained from 23 patients and were analyzed by genomic restriction enzyme analysis, arbitrarily primed PCR fingerprinting, (random amplified polymorphic DNA analysis), and/or restriction of specific PCR-amplified genes (restriction fragment length polymorphism analysis). A single strain was found in sequential biopsy specimens from 12 of 15 patients (80%) receiving sucralfate. In the remaining three patients treated with sucralfate, two strains were identified in two patients and three strains were identified in the third patient. In contrast, a single strain was found in sequential biopsy specimens from only three of eight patients (37%) receiving bismuth, metronidazole, and nitrofurantoin. Two strains were identified in five other patients receiving bismuth-antibiotic (63%). Immunoglobulin G antibodies to H. pylori were present in the sera of all patients. Thus, H. pylori colonization can persist for long periods (up to at least 4 years), despite high titers of immunoglobulin G antibodies in serum. Resistance to metronidazole was noted in some strains before and/or after treatment, but all strains remained susceptible to amoxicillin, tetracycline, and nitrofurantoin. We conclude that H. pylori genotypes, as measured by several sensitive DNA fingerprinting methods, can remain stable for years in vivo, despite the acquisition or loss of drug resistance, circulating antibody, or exposure to antibiotics or sucralfate. PMID- 7790464 TI - Parasitic culture of buffy coat for diagnosis of visceral leishmaniasis in human immunodeficiency virus-infected patients. AB - Two samples of buffy coat from the peripheral blood of 25 human immunodeficiency virus-positive patients with proven visceral leishmaniasis, as determined with a bone marrow aspirate (stain and culture), were cultured onto Schneider's and Novy McNeal-Nicolle media. Hemoculture positivity was 67%. The average growing time was 10 days. This is an easy, noninvasive, and sensitive technique. PMID- 7790463 TI - In vitro culture and serologic and molecular identification of Septata intestinalis isolated from urine of a patient with AIDS. AB - Microsporidian spores were identified, on the basis of Weber's staining, in urine, stool, nasal, and saliva samples of an AIDS patient with diarrhea, hematuria, dysuria, and dementia. Urine and stool samples contained numerous spores, whereas few spores were seen in the nasal and saliva samples. Spores were concentrated from urine samples and inoculated into monkey kidney cell (E6) monolayers. After 6 to 8 weeks of culture, infected E6 cells filled with spores as well as spores free in the culture supernatants were seen daily. Transmission electron microscopy revealed that all stages of the parasite (CDC:V297) developed within septated, honeycomb-shaped parasitophorous vacuoles. Indirect immunofluorescence and immunoblotting studies using rabbit anti-Encephalitozoon cuniculi, anti-Encephalitozoon hellem, and anti-CDC:V297 sera revealed that CDC:V297 reacted intensely with the homologous serum but minimally with the heterologous sera. DNA isolated from CDC:V297, when PCR amplified with E. hellem and E. cuniculi primers, did not produce the diagnostic bands of approximately 547 and approximately 549 bp characteristic of E. hellem and E. cuniculi, respectively. On the basis of these studies, we concluded that CDC:V297 fits the description of Septata intestinalis (A. Cali, D. P. Kotler, and J. M. Orenstein, J. Eukaryot, Microbiol. 40:101-112, 1993). PMID- 7790465 TI - Comparison of commercially available enzyme immunoassay with traditional serological tests for detection of antibodies to Coccidioides immitis. AB - A newly released commercially available enzyme-linked immunosorbent assay (ELISA) was evaluated for its ability to detect immunoglobulin M (IgM) and IgG antibodies against the tube precipitin and complement fixation (CF) antigens of Coccidioides immitis. The ELISA was compared with more traditional diagnostic assays, CF, latex agglutination (LA), and immunodiffusion (ID). When the IgM-specific portion of the ELISA was compared with LA, there was an agreement of 81.8%, a specificity of 75.0%, and a sensitivity of 84.6%. For the determination of the presence of IgG antibodies, the results of the IgG-specific part of the ELISA were compared with the combined results of ID and CF. After resolution of discrepant results, there was an agreement of 95.6%, a specificity of 98.3%, and a sensitivity of 92.6%. When the results of the IgG- and IgM-specific portions of the ELISA combined were compared with the results of the three traditional assays (CF, LA, and ID) there was an agreement of 96.7%, a specificity of 98.5%, and a sensitivity of 94.8%. The ELISA proved to be a reliable assay for the detection of antibodies against the tube precipitin and CF antigens and did not suffer from the objectivity required to interpret the results of the traditional assays and anticomplement interference associated with the traditional assays. PMID- 7790466 TI - PCR typing of field isolates of Plasmodium falciparum. AB - We report on an analysis of the constraints of PCR typing of field Plasmodium falciparum isolates by using a few highly polymorphic markers, MSA-1, MSA-2, TRAP, and CS. We show that the reactions are specific for the P. falciparum species. The detection threshold (minimum number of parasites required to detect a visible band by ethidium bromide) differed from one marker to the other and, within one locus, from one primer combination to the other. Importantly, the various MSA-1 and MSA-2 reference alleles were amplified with the same efficiency. Amplification from reconstituted allele mixtures indicated that at certain allele ratios, the most abundant allele interfered with the amplification of the less abundant one. An analysis of nine isolates collected from patients with acute malaria in Dielmo, Senegal, during a transmission season when the inoculation rate was one infective bite every second night is presented and discussed. All samples contained more than one parasite type. A significant polymorphism was observed for the four markers. Novel TaqI restriction fragment length polymorphisms were found for the TRAP gene, and TRAP gene typing alone allowed a distinction between the various isolates. MSA-1 and MSA-2 gave multiple band patterns specific for each sample. PMID- 7790467 TI - Identification and characterization of outer membrane proteins of Pasteurella multocida serotype D by using monoclonal antibodies. AB - Monoclonal antibodies (MAbs) against Pasteurella multocida serotype D were obtained by fusion of spleen cells from BALB/c mice immunized with outer membrane proteins (OMPs) with SP2/0-Ag 14 murine myeloma cells. Desirable MAbs were selected by enzyme-linked immunosorbent assay (ELISA) with OMP as the antigen. MAbs MT1 and MT2 identified two different proteins (H [heavy] and W [weak]), each with a molecular mass of 32 kDa, in Western blots (immunoblots). Treatment of the OMPs with proteolytic enzymes and sodium periodate indicated that the binding sites of MAbs MT1 and MT2 are of protein and glycoprotein natures, respectively. The epitopes reactive with MAbs were surface exposed, as visualized by immunoelectron microscopy. Among field isolates of P. multocida serotype D, two distinct OMP patterns were recognized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and these patterns were designated types I and II. In both the ELISA and the Western blot, MAb MT1 recognized only type I isolates, whereas MAb MT2 recognized both type I and II isolates. Neither MAb MT1 nor MAb MT2 reacted with either reference strains of capsular serotypes A, B, E, and F or field isolates of capsular serotype A of P. multocida. This is the first report of MAbs identifying the serotype D-specific OMP of P. multocida. PMID- 7790468 TI - Effect of ambient temperature on competence of deer ticks as hosts for Lyme disease spirochetes. AB - We determined whether the temperature of extrinsic incubation affects the competence of vector ticks as hosts for Lyme disease spirochetes (Borrelia burgdorferi). Larval Ixodes dammini ticks that had engorged on spirochete infected C3H mice were incubated continuously at various temperatures, and the gut contents of the resulting nymphs were examined for spirochetes by direct immunofluorescence microscopy. Spirochetes were present in virtually all nymphs kept at 27 degrees C or less for 6 months, in only 10% of those kept at 33 degrees C, and in none kept at 37 degrees C. Spirochetes became undetectable within 8 weeks when nymphs were warmed from 27 to 33 degrees C beginning at the time of molting. Nymphs became virtually noninfective for mice after incubation at temperatures higher than 27 degrees C for 2 weeks or longer. We conclude that ambient temperatures in excess of 27 degrees C are not permissive for transmission of the agent of Lyme disease. PMID- 7790469 TI - Microtitration plate enzyme immunoassay to detect PCR-amplified DNA from Candida species in blood. AB - We developed a microtitration plate enzyme immunoassay to detect PCR-amplified DNA from Candida species. Nucleotide sequences derived from the internal transcribed spacer (ITS) region of fungal rDNA were used to develop species specific oligonucleotide probes for Candida albicans, C. tropicalis, C. parapsilosis, and C. krusei. No cross-hybridization was detected with any other fungal, bacterial, or human DNAs tested. In contrast, a C. (Torulopsis) glabrata probe cross-reacted with Saccharomyces cerevisiae DNA but with no other DNAs tested. Genomic DNA purified from C. albicans blastoconidia suspended in blood was amplified by PCR with fungus-specific universal primers ITS3 and ITS4. With the C. albicans-specific probe labeled with digoxigenin, a biotinylated capture probe, and streptavidin-coated microtitration plates, amplified DNA from a few as two C. albicans cells per 0.2 ml of blood could be detected by enzyme immunoassay. PMID- 7790471 TI - Controlled evaluation of BacT/Alert standard aerobic and FAN aerobic blood culture bottles for detection of bacteremia and fungemia. AB - A new medium, FAN, designed to enhance the recovery of microorganisms, has been developed for the BacT/Alert blood culture system (Organon Teknika Corp., Durham, N.C.). We compared the yield and speed of detection of microorganisms in 6,847 adequately filled paired aerobic standard and FAN bottles at four university hospitals. Of 499 clinically significant microorganisms isolated from one or both bottles, significantly more Staphylococcus aureus isolates (P < 0.001), coagulase negative staphylococci (P < 0.001), yeasts (P < 0.01), and all microorganisms combined (P < 0.001) were recovered from the FAN bottles. Overall, the speeds of detection of positive cultures did not differ between the two medium formulations; mean times to detection in the standard and FAN bottles were 16.1 and 16.0 h, respectively. When a subset of patients on antimicrobial therapy was evaluated, significantly enhanced yield from the FAN bottle was evident for staphylococci. Overall, the FAN bottle outperformed the standard aerobic BacT/Alert bottle. PMID- 7790470 TI - Controlled study of Escherichia coli diarrheal infections in Bangladeshi children. AB - Diarrheal diseases are highly prevalent in Bangladesh. However, the relative contribution of diarrheagenic Escherichia coli organisms--those that are enterotoxigenic (ETEC), enteropathogenic (EPEC), enteroinvasive, enterohemorrhagic, enteroaggregative, and diffuse adherent--to diarrhea in Bangladeshi populations is not known. With DNA probes specific for these diarrheagenic E. coli strains, we analyzed fecal E. coli from 451 children up to 5 years of age with acute diarrhea seeking treatment at a Dhaka hospital and from 602 matched control children without diarrhea from July 1991 to May 1992. Enteroinvasive E. coli was not isolated from any children; enterohemorrhagic E. coli was not isolated from any diarrheal children but was isolated from five control children; enteroaggregative and diffuse adherent E. coli strains were isolated with similar frequencies from children with and without diarrhea, thereby showing no association with diarrhea; ETEC was significantly associated with diarrhea in the diarrheal children as a whole and especially in the age groups of 0 to 24 months and 37 to 48 months (further analysis suggests an association with diarrhea for the heat-stable toxin only and for both heat-labile and heat-stable-toxin-producing ETEC only); and EPEC was significantly associated with diarrhea in the diarrhea group as a whole and particularly in infants up to 1 year of age. Further analysis suggested that EPEC strains of only the traditional serogroups were significantly associated with diarrhea. ETEC and EPEC infections peaked during warm months. Our data thus suggest that EPEC and ETEC are important causes of acute diarrhea in children in this setting. PMID- 7790472 TI - Specific antibody detection in invasive aspergillosis by analytical isoelectrofocusing and immunoblotting methods. AB - Aspergillus fumigatus antigens have been tested to determine their potential as aids in the diagnosis of invasive aspergillosis (IA). Immunoglobulin G (IgG) antibodies to these antigens were detected by analytical isoelectrofocusing in conjunction with immunoblotting. A total of 12 antigenic fractions, including culture filtrates and surface and mycelial extracts of A. fumigatus, were investigated. Eleven were reactive with serum specimens from patients with aspergilloma, which served as positive controls for the evaluation of a specific IgG response. Eight of 12 antigens showed good responses with serum specimens from patients with allergic bronchopulmonary aspergillosis, which were used to assess the sensitivity of IgG detection. No measurable reactivity was detected in 18 negative control serum specimens, while 11 of 13 patients with proven, highly probable, or probable cases of IA had anti-Aspergillus IgG to multiple antigenic preparations. Patients with IA who were capable of mounting a substantial humoral response to Aspergillus antigens gave an antibody profile with five antigenic preparations which seemed to be characteristic of the disease. Data show that this method is highly sensitive and may allow the selection of fractions which are both highly antigenic and specific for the detection of antibodies to Aspergillus antigens. They also indicate that the use of a spectrum of antigenic molecules is advisable, given the variability observed in the immune responses of individual patients. PMID- 7790473 TI - Analysis of Salmonella enteritidis isolates by arbitrarily primed PCR. AB - An arbitrarily primed PCR (AP-PCR) was developed to analyze the genomic DNAs of Salmonella enteritidis isolates from human outbreaks and from avian sources. The AP-PCR generated seven distinct randomly amplified DNA patterns among the S. enteritidis isolates studied. Differences in the DNA patterns among isolates of S. enteritidis phage types 13a and 8 as well as among S. enteritidis phage type 14b were observed. The AP-PCR analysis can be used to determine the differences among isolates within the same phage types and may be useful for tracing back the source of S. enteritidis outbreaks in humans more precisely. PMID- 7790475 TI - Oxygen as limiting nutrient for growth of Cryptococcus neoformans. AB - In microbroth cultures with RPMI 1640 medium, the growth yield of seven Cryptococcus neoformans isolates was unaffected by augmentation of the normal (0.2%) glucose concentration in the medium to 2%, and the addition of other potential carbon, nitrogen, and vitamin sources to the medium also failed to produce large changes in growth yield. However, macrobroth cultures of C. neoformans in RPMI 1640 that were agitated by rotation in air gave turbidities 6 to 37 times greater than those in identical cultures incubated statically, and similar levels of increase were seen whether the medium contained 0.2 or 2% glucose. Incubation of microplates under an oxygen atmosphere or with agitation by rotation led to an increase of up to twofold in growth turbidity of the yeast. The maximum increase was achieved by incubation with rotation and was dependent on the brand of microplate used. The findings implicate oxygen as a growth limiting nutrient for C. neoformans. Incubation of microbroth cultures under conditions that enhance oxygen availability for antifungal susceptibility testing purposes may increase the speed of such tests and enhance the determination of MIC endpoints. PMID- 7790476 TI - Case report of and description of parasite in Mammomonogamus laryngeus (human syngamosis) infection. AB - About 100 cases of human infections with Mammomonogamus laryngeus (Syngamidae, Syngaminae) have been reported, with virtually all cases originating in the Caribbean Islands and Brazil. This report describes the fifth patient in North America infected with M. laryngeus and the first case documented to originate in Jamaica. The patient complained of a characteristic persistent nonproductive cough and a lump in her throat. M. laryngeus is a nematode in which the male and female are permanently joined in copula, producing a distinctive Y shape. Since there is scant clinical information about this parasite, this report includes a description of the adult worms and eggs, a summary of the epidemiology, and the clinical manifestations in humans. Illustrations are presented to facilitate future identification of this parasite and to expedite treatment. PMID- 7790474 TI - Characterization of the bovine group A rotavirus strain neonatal calf diarrhea virus-Cody (NCDV-Cody). AB - The neonatal calf diarrhea virus-Cody (NCDV-Cody) strain was found to contain a mixture of rotaviruses with G6 and G8 VP7 genes. Challenge exposure of calves with the mixed virus inoculum indicated that both viruses were maintained by passage in vivo. This is the first P1:G8 rotavirus to be characterized in cattle in the United States. PMID- 7790477 TI - Management of patellar instability. PMID- 7790478 TI - Operative realignment of patellar malalignment in children. AB - Realignment operations were performed on 57 knees to correct patellar malalignment in children between 1985 and 1991. Three different operative techniques were used: the lateral release, the lateral release and medial reefment, and the Roux-Goldthwait patellar tendon transposition. Roentgenographic values were measured before and after the operation by Laurin's method. The mean follow-up time was 4 years 2 months, after which 20 knees were excellent, 20 good, 11 fair, and six poor, according to Insall's criteria. The effect of the operation on pathological roentgenographic values was obvious, and the malalignment of the patella was in most cases corrected. There are differences in the improvement effected by these three techniques. The lateral release and medial reefment correct the patellar tilt most effectively, and the Roux Goldthwait operation, the lateral patellar deviation. The lateral release seems to be the appropriate technique for mild malalignment. PMID- 7790479 TI - Reconstruction of mid-substance anterior cruciate rupture in adolescents with open physes. AB - Five cases of anterior cruciate ligament reconstruction, performed for symptomatic episodes of giving way or during surgery for associated injury, were carried out in preepiphyseal closure adolescents (ages 12-15 years), utilising a strip of iliotibial band placed over the top of the lateral femoral condyle in a MacIntosh type repair, and avoiding drilling through epiphyseal plates. At a mean follow-up of 4.4 years, all five were symptomatically satisfactory and all five patients had returned to their preinjury level of sports activity. Although objective assessment revealed that increased laxity, when compared to the normal leg anterior laxity measured by the KT-1000, was within normal limits in four of five patients. Only one patient, who had had a fracture of the contralateral femur, had any leg length discrepancy. PMID- 7790480 TI - Periarticular fractures after manipulation for knee contractures in children. AB - We report two cases, each of which sustained two separate periarticular fractures from overzealous manipulation for knee contracture. The four fractures reported in this study involve one normal child sustaining asynchronous ipsilateral distal femoral and proximal tibial fractures and a child with the diagnosis of amyoplasia sustaining bilateral proximal tibial fractures. The child with knee contracture must be treated carefully and not exposed to overzealous physiotherapy or manipulation. The child who has developed a joint contracture secondary to lengthy immobilization may be at increased risk for periarticular fracture secondary to disuse osteopenia. The knee joint is at particular risk because of the long lever arm of the leg. These concerns should be conveyed to anyone involved in the patient's care, including the parents, therapists, nurses, and physicians. Passive range of motion in the child should never be painful. Normal children often can obtain maximal range of motion if left alone and not restricted. PMID- 7790481 TI - Tibial tuberosity excision for symptomatic Osgood-Schlatter disease. AB - A modified Ferciot procedure was used to excise the tibial tubercle in patients with persistently symptomatic Osgood-Schlatter disease. Forty-two knees in 35 patients were reviewed at a mean follow-up of 5 years to assess outcome. The results revealed relief of pain in 95% of patients and reduction of prominence in 85.5% with minimal complication, in particular no evidence of genu recurvatum. The pathogenesis of the condition is outlined, and some of the theories and treatment modalities discussed. Tibial tubercle excision is recommended as the treatment of choice in those few cases that fail with conservative treatment. PMID- 7790482 TI - Determination of skeletal age in children with Osgood-Schlatter disease by using radiographs of the knee. AB - We determined the skeletal age in 26 children (12 girls, 14 boys) with Osgood Schlatter disease using knee radiographs. The average chronological age was 13.2 +/- 2.2 years, and the average bone age was 13.1 +/- 2.3 years (p > 0.01). All but one of the skeletal ages fell within the normal range. Skeletal maturation in children with Osgood-Schlatter disease is thus normal. With normal skeletal maturation and normal physes histologically (previously shown), it is unlikely that an abnormality of physeal development or structure is the etiology of Osgood Schlatter disease. Rather, it is most likely a result of tensile stresses on the tibial tuberosity. This is in contrast to slipped capital femoral epiphysis, another common disorder affecting children of the same ages as those with Osgood Schlatter disease, in which physeal abnormalities and skeletal maturation anomalies do occur. PMID- 7790483 TI - Bipolar infrapatellar tendon rupture. AB - Traumatic patella alta in children occurs either distal to the patellar tendon as a tibial tubercle apophyseal fracture or proximally as an osteochondral sleeve fracture of the inferior patellar pole. Acute surgical exploration in a pediatric case of a knee extensor mechanism rupture revealed both proximal and distal (bipolar) patellar tendon pathology. PMID- 7790484 TI - MRI of focal fibrocartilaginous dysplasia. AB - Focal fibrocartilaginous dysplasia (FFCD) is an uncommon, benign condition associated with unilateral tibia vara in young children. The clinical, pathologic, plain film, and magnetic resonance imaging (MRI) findings of FFCD were reviewed in two children. MRI findings were virtually identical in both patients and correlated well with the plain film and pathologic findings. We believe that FFCD has a typical MRI appearance. However, FFCD also has characteristic plain film findings, and when these are present, MRI is indicated for only an atypical clinical presentation. PMID- 7790486 TI - Osteochondritis dissecans of the femoral head in children and adolescents: a report of 17 cases. AB - Osteochondritis dissecans of the femoral capital epiphysis is uncommon and is usually reported as a case report or in association with other diseases. This study reports 17 cases with the primary underlying diagnosis of Legg-Calve Perthes disease in seven, idiopathic in six, avascular necrosis following trauma in three, and avascular necrosis with previous infection in one. Twelve cases had long-term follow-up. Two cases in which no surgery was performed were followed for an average of 12.5 years; 10 cases in which surgery was performed were followed for an average of 16.1 years. Excision of the osteochondritis fragment was performed in six cases. It was necessary only to dislocate the hip to excise the lesion in five cases. No morbidity resulted from temporary surgical dislocation. Excision of the osteochondritis dissecans fragment allowed these six patients to return to fairly normal living during the time of follow-up. PMID- 7790487 TI - Diagnostic and therapeutic arthroscopy of the hip in children and adolescents: evaluation of results. AB - Twenty-four arthroscopies of the hip performed at the Alfred I. duPont Institute, Wilmington, Delaware, in 21 patients between 1981 and 1991 were retrospectively studied. The average age of patients at the time of arthroscopy was 16 years (range, 11-21 years). The arthroscopies were diagnostic if the procedure was performed to visualize the hip or to perform a synovial biopsy and therapeutic if the procedure was performed to treat a suspected intra-articular abnormality. There were eight diagnostic arthroscopies and 16 therapeutic arthroscopies. The arthroscopy correlated with the presumptive causes of symptoms in 13 hips (54%) and failed to correlate in 11 hips (46%). Two patients had complications of transient pudendal nerve dysesthesia with full recovery. There were no infections or residual hip stiffness. A diagnostic arthroscopy is not helpful as a confirming diagnostic procedure. Arthroscopy of the hip is helpful in obtaining synovial biopsies and allows loose body removal, thus obviating the need for open surgery and intraoperative dislocation of the hip. PMID- 7790485 TI - Complications in proximal tibial osteotomies in children with presentation of technique. AB - Proximal tibial osteotomies in children have been associated with a number of complications, including peroneal nerve palsies, compartment syndromes, deep and superficial infections, vascular injuries, iatrogenic fractures, apophyseal or growth plate damage, and recurrence of deformity. A retrospective review of the results of 22 children who had 30 primary and seven repeat proximal tibial osteotomies was performed to assess the frequency of complications at our institution. Using a specified technique that included prophylactic anterior compartment fasciotomy and distal fibulectomy, there were three superficial wound infections and one delayed union but no peroneal nerve palsies, vascular injuries, compartment syndromes, or fixation failures. There were no sequelae from the superficial infections. This is a lower rate of complications than previously reported in the literature and suggests a relationship to our current surgical technique and attention to detail. We believe that proximal tibial osteotomies can be performed successfully and safely in children when the surgeon recognizes the potential problems and takes steps to prevent them. PMID- 7790488 TI - Neonatal hip instability: screening with anterior-dynamic ultrasound method. AB - The anterior-dynamic ultrasound method was used for screening 4,430 children for hip dislocation. The frequency of treatment for unstable hip joints was reduced to 0.18%, having been 1.7% without ultrasound screening. No cases of late diagnosed dislocation were registered. The sensitivity of the pediatricians' clinical examination screening was low, only 24%. After intensive training over several years and improved clinical examination methods, our five technicians managed to increase the sensitivity to 53%. With clinical examination methods, cases of totally dislocated hips can be difficult to diagnose, and only two of four such hips were clinically diagnosed; the proportion of false-positive cases, 0.7%, was also considerable. The anterior-dynamic ultrasound method could optimize the screening results of many clinics. PMID- 7790491 TI - Coxa magna after open reduction for developmental dislocation of the hip. AB - We studied coxa magna after open reduction of developmental hip dislocation, including the etiology, incidence, and influence on the long-term results and acetabular development. Forty-seven hips in 47 patients were radiographically examined for at least 10 years, and another 20 hips in 20 patients were examined arthrographically at an early stage after open reduction. At follow-up, the incidence of coxa magna, which was defined as a femoral head with a size > or = 20% greater than the opposite side, was 34.0%, and that seemed to be one of factors that worsened the long-term results. One of the most important causes of coxa magna is to overwiden the acetabular capacity by excising the limbus; another cause is the surgical invasion and synovitis of the hip joint after operation. PMID- 7790490 TI - One-stage treatment of congenital dislocation of the hip in older children. AB - We reviewed the results of a primary one-stage combined operation in 47 patients (55 hips) who were > or = 4 years and had congenital dislocation of the hip. At a mean follow-up of 7.5 years (2-16 years), 67% of the whole series had good or excellent clinical results, and 65% were good or excellent radiologically. Avascular necrosis occurred in four patients, and redislocation also occurred in four patients. We concluded that most of the children who are > or = 4 years and who have congenital dislocation of the hip can successfully be treated with an extensive one-stage operation consisting of open reduction combined with innominate osteotomy and femoral varus, derotation, and shortening osteotomy. PMID- 7790489 TI - Ultrasonography and developmental dysplasia of the hip: a cost-benefit analysis of three delivery systems. AB - The role of ultrasound (US) in the diagnosis and management of infants with developmental dysplasia of the hips (DDH) is becoming widely accepted. In our community, there exist three delivery systems for US-DDH: the radiology based, the combined radiology/orthopaedic based, and the orthopaedic office based. This study reviewed the costs and benefits of each delivery system and found that once expertise had been gained and start-up costs were met, the orthopaedic office based system was the most convenient, efficient, and cost effective for the patient/family and treating physicians. This mirrors the experience of cardiologists, obstetricians, and family practitioners, fields in which the utility of office-based ultrasonography is widely recognized and has become the standard. PMID- 7790492 TI - Pelvic remodeling after Salter osteotomy. AB - Salter innominate osteotomy is a widely used operative procedure to redirect the acetabulum in cases of acetabular dysplasia. The effectiveness of this redirection is indicated by the change in the appearance of the obturator foramen after the procedure. This is usually accompanied by an increase in the center edge (CE) angle with an effective decrease in the forces transmitted across the hip joint. In a prospective study of 20 Salter innominate osteotomies performed on two different age groups, one mature and one immature, we studied the change in the deformity of the obturator foramen with time after this procedure. In the immature pelvis, the asymmetric appearance of the obturator foramen remodeled gradually during the 6 months after the procedure. However, in the mature patient, no such remodeling potential was demonstrable during the study period. This finding has clinical implications regarding the advice for performing Salter innominate osteotomies in mature and immature patients. PMID- 7790493 TI - Distal transfer of the greater trochanter revisited: long-term follow-up of nine hips. AB - Seven female patients (nine hip joints) with avascular necrosis and functional coxa vara secondary to developmental dysplasia of the hip joint (DDH) were treated by distal transfer of the greater trochanter (DTT). A 5-year follow-up showed good results in 89% of the hip joints. We reviewed the patients again 12 years later using the Mayo Clinic hip score. Improvement of gait was maintained in the majority of the patients (71%), but the hip score was low in 67% of the patients because of the development of osteoarthritis. Two patients underwent a total hip arthroplasty, and a third is awaiting this operation. Distal transfer of the trochanter is beneficial in improvement of gait but may enhance the development of osteoarthritis. PMID- 7790494 TI - Slipped capital femoral epiphysis associated with endocrine disorders. AB - We reviewed 85 patients with endocrine disorders and slipped capital femoral epiphysis (SCFE). The disorders were hypothyroidism (40%), growth hormone deficiency (25%), and others (35%). The average age at diagnosis of the disorder was 13.2 +/- 6.2 years and 15.3 +/- 5.3 years at diagnosis of the first SCFE. In 53 hips, the bone and chronologic age were both known: 11.6 +/- 3.0 years bone age, 16.5 +/- 6.5 years chronologic age, p < 0.01. The age at presentation of the first SCFE ranged from 7-35 years; only those with hypothyroidism or growth hormone deficiency were < 10 years of age; all patients with other endocrinopathies, when seen first with an SCFE at an atypical age, were > 16 years. The hypothyroid patients usually had the endocrine diagnosis made at presentation of the first SCFE; the growth hormone-deficient children usually had the endocrine diagnosis made before that of the SCFE (p < 0.01). None of those in whom the diagnosis of the endocrine disorder occurred after the diagnosis of the SCFE was hypothyroid or growth hormone deficient. All hypothyroid patients developed the first SCFE before or during hormonal supplementation; 92% with growth hormone deficiency developed the SCFE during or after supplementation (p < 0.01). Because the prevalence of bilaterality was 61% (p < 0.01), prophylactic treatment of the opposite hip should be considered. PMID- 7790495 TI - Epiphyseal growth after pinning of slipped capital femoral epiphysis. AB - Seventy-seven hips in 61 patients (mean age, 13 years) with slipped capital femoral epiphysis treated with in situ pinning were retrospectively evaluated to determine the frequency and magnitude of epiphyseal growth after pinning. Threaded Steinmann pins, Knowles pins, and cannulated screws were used. Evidence of the epiphysis "growing off" the pins was seen in 29 and 18% of the hips treated with Steinmann and Knowles pins, respectively. No hips with cannulated screws continued to grow after surgery. The use of one cannulated screw in the treatment of mild and moderate slipped capital femoral epiphysis is recommended. PMID- 7790496 TI - Legg-Calve-Perthes disease in the evolutionary period: comparison of magnetic resonance imaging with bone scintigraphy. AB - Magnetic resonance images (MRIs) and pinhole scintigraphs were obtained in 40 patients (40 hips) with Legg-Calve-Perthes disease in the evolutionary phase, the mean age at onset of symptoms being 6 years 7 months. The correlation between the uptake of the pinhole scintigraphs and the signal intensity of MRIs was examined in reference to the extent of the involved femoral epiphysis. MRIs depicted the extent of the involved femoral epiphysis more clearly than did pinhole scintigraphs. The uptakes of the pinhole scintigraphs corresponded with high or normal intensity of T2-weighted images on MRI. The femoral epiphysis in the initial phase (in which the signal intensity of the lateral area of the epiphysis on T1-weighted coronal images was low or intermediate and high or unchanged on T2 weighted coronal images corresponded to the lateral column [recanalization] on the pinhole scintigraphs) suggested a low risk of subsequent deformity. MRI is a powerful new technique to evaluate the femoral epiphysis in Legg-Calve-Perthes disease. PMID- 7790497 TI - Late hip subluxation in spastic diplegia associated with unrecognized hydrocephalus. AB - Problematic hip subluxation is uncommon in spastic diplegia. We have identified three cases of late hip subluxation in teenage children with spastic diplegia associated with unrecognized hydrocephalus or ventriculoperitoneal shunt dysfunction. Each was a community ambulator with radiologically stable hips in childhood, but in adolescence underwent a deterioration in ambulatory status associated with rapid hip subluxation. Subsequent investigation revealed undiagnosed hydrocephalus in one patient and shunt dysfunction requiring revision in the other two. Surgery was performed in all three cases to control the hip subluxation. The atypical presentation of a progressively unstable hip in an ambulatory spastic diplegic patient may indicate the presence of previously unrecognized raised intraventricular pressure. PMID- 7790498 TI - Chiari pelvic osteotomy in cerebral palsy. AB - Hip subluxation and dislocation in patients with cerebral palsy are challenging problems. The Chiari pelvic osteotomy has been commonly recommended as a technique for hip stabilization when acetabular dysplasia is present. We evaluated the results of Chiari osteotomy without concomitant femoral osteotomy in 24 hips in 23 patients with an average follow-up of > 7 years. Evaluation consisted of a pain and function questionnaire, chart review, physical examination, and review of serial radiographs. At final follow-up, 19 of 24 (79%) of the hips were painless, and 21 of 24 hips (88%) permitted unlimited sitting. Seven of 24 (29%) of hips, however, had a migration index of > or = 30%. Painful hips were associated with a greater migration index preoperatively, at 1 year postoperatively, and at final follow-up, and a greater height of the osteotomy above the edge of the acetabulum. Deterioration in the migration index (resubluxation) occurred largely in the first year postoperatively. Alternative acetabular procedures, simultaneous femoral osteotomies, or both may improve on these results. Long-term follow-up studies are necessary to compare the results of different treatments for spastic hip subluxation and dislocation to determine optimal treatment. PMID- 7790499 TI - Hip pathology in the trichorhinophalangeal syndrome. AB - Up to 50% of individuals with trichorhinophalangeal syndrome may have Perthes like hip changes. Thirteen hips in nine skeletally immature patients were studied. Follow-up averaged 4.7 years. The patients were categorized as juvenile (4-8 years) and adolescent (12-14 years) according to their age at presentation. The universal severity of involvement, often older age at presentation, and disproportionate number developing severe deformity with hinge abduction and pain in adolescence distinguished these patients from those with true Perthes' disease. Whether the process can be modified significantly to produce a better outcome is unclear, but management must be directed at avoiding the development of hinge abduction. PMID- 7790501 TI - 29th Annual meeting of the Scoliosis Research Society. Portland, Oregon, September 21-24, 1994. Abstracts. PMID- 7790502 TI - The role of free pericranium grafts in augmentation rhinoplasty. AB - Various tissues and materials have been used in augmentation rhinoplasty. This paper presents a retrospective analysis of 14 patients, 8 female and 6 male, in whom free pericranium grafts were used in order to restore postsurgery or posttraumatic nasal defects. There were no complications from either the donor or the recipient site. The early and medium term results were satisfactory. It is concluded that free pericranium, compared with other autografts, is a good alternative due to its several advantages and hardly any disadvantages. In selected cases it can even be the material of choice. PMID- 7790500 TI - The prevention of skin excoriation under children's hip spica casts using the goretex pantaloon. AB - The purpose of this study is to determine whether the use of the Goretex Pantaloon cast liner for children's spica casts reduces urine excoriation of the skin under the cast and reduces the incidence of unplanned cast changes necessitated by cast soilage. Between 1988 and 1993, 72 consecutive children who had 147 hip spica casts applied were followed. The first 36 patients had 77 spica casts applied without the Goretex Pantaloon, and the last 36 patients had 70 spica casts with a Goretex liner. In the group of patients without Goretex, 22% of casts were associated with urine excoriation of the skin compared to 1.4% in the group of patients who had a Goretex liner applied. This was statistically significant (p = 0.0005). The incidence of unnecessary cast changes due to soiling of the cast was 14% in the non-Goretex group compared to 2.9% in the Goretex group (p = 0.05). The use of the Goretex liner in our series resulted in a savings of $38 per cast including the cost of the liners ($75). The Goretex Pantaloon cast liner used for children's spica casts prevents urine excoriation of the skin and is cost effective. PMID- 7790503 TI - Rhinoplasty with nasal bone disarticulation to deepen the nasofrontal groove. Experimental and clinical results. AB - Deepening of the nasofrontal groove is considered a fiddly task. The unwonted chisel ostectomy technique (Skoog, 1974; McCarthy, 1990; Aiach and Levignac, 1991) was therefore modified and evaluated both experimentally and clinically. The hump is removed in one piece together with the nasal bones up to the horizontal part of the frontonasal suture. To accomplish this, the reduction osteotomy has to be performed in a wave line fashion. The depth of resection in the sellion area depends upon the aesthetic planning. In cases with most severe hypertrophy, the osteotome enters the vertical frontonasal suture behind the nasal bones and in front of the nasal spine of the frontal bone. The nasal bones are disarticulated with a levering movement. Cadaver studies demonstrate the safety of the technique: no fracture lines were detected in the frontal process of the maxilla, ethmoid, frontal or lacrimal bones, by either clinical inspection, or by standardised radiological examination. The clinical cases show a convincing outcome. PMID- 7790504 TI - Screening bone scintigraphy in the staging of locally advanced head and neck cancer. AB - A retrospective determination of the yield from screening bone scintigraphy in detecting bone metastasis when used for disease staging of 93 asymptomatic patients with locally extensive head and neck cancer was undertaken. The bone scintigraphy findings were correlated with observations from other radioimaging studies done within 1 month of head and neck cancer diagnosis. Bone scintigraphy did not reveal a single case of bone metastasis outside the head and neck region. On the other hand, 3 cases (8%) of resectable and 2 cases (5%) of non-resectable bone metastasis located within the head and neck area were observed among the 40 patients with abnormal bone scintigraphy. Old rib fracture or degenerative disease was responsible for the increased radionuclide uptake in bony areas below the clavicle in less than half of the remaining 35 cases. We conclude that the routine use of bone scintigraphy for disease staging in asymptomatic patients with locally advanced head and neck cancer is not warranted because the positive yield is low. PMID- 7790505 TI - Submandibular swelling as the first manifestation of giant cell arteritis. Report of a case. AB - Giant cell arteritis is a systemic disease with a broad range of clinical signs and symptoms. Although the most frequently involved vessel is the superficial temporal artery, other arteries can be affected. Vasculitic changes in the facial artery usually present as jaw claudication. A report of a case of giant cell arteritis is presented in which facial artery involvement first manifested itself clinically as a submandibular mass. This is a very rare and atypical form of clinical presentation. PMID- 7790506 TI - Stability testing of a two miniplate fixation technique for mandibular angle fractures. An in vitro study. AB - In the case of mandibular angle fractures, a two miniplate fixation technique in which one plate is applied ventral to the oblique line and a second plate at the inferior border of the buccal cortex was used to stabilize the fracture. In this paper, the stability of the two miniplate fixation technique was tested in a three-dimensional in vitro model. The results of this study showed that in cases of angle fractures this fixation technique provides stable fixation under functional loading. PMID- 7790507 TI - Temporoparietal fascial flap in reconstruction of the cranio-maxillofacial area. PMID- 7790508 TI - Life-threatening bleeding following maxillofacial trauma. PMID- 7790509 TI - Anterior cranial base reconstruction using a hydroxyapatite-tricalciumphosphate composite (Ceratite) as a bone substitute. AB - The craniofacial approach to cranial base tumors has widened the operability of tumors with intracranial invasion. However, the resulting skull base defect must be reconstructed adequately to prevent postoperative morbidity and mortality. We use hydroxyapatite-tricalciumphosphate ceramic (Ceratite) as a bone substitute material to reconstruct the skull base defect in combination with the pericranial flap, ensuring separation between the sinonasal cavity and epidural cavity. Although the nasal surface of the Ceratite block is left exposed directly to the sinonasal cavity, it was shown to be epithelialized within 6 months postoperatively. Our method is less invasive than any other conventional method and may offer more chance of curative resection of tumors with anterior skull base invasion. PMID- 7790511 TI - Diagnostic accuracy of TMJ arthroscopy in correlation to histological findings. AB - From 1987-1993, 356 arthroscopic examinations of the temporomandibular joint were performed on 295 patients. During 69 examinations, biopsies were obtained to correlate arthroscopic findings with histology. In the overall group, histology confirmed in 78.9% the arthroscopic findings. Correlation was better in joints with degenerative changes (81.5%) than in those with a synovitic/hyperaemic appearance (61.5%). Chondroid metaplasia, detritus synovitis and synovial chondromatosis were additional diagnoses given by histological examination. In 11 joints, open arthrotomy was performed after arthroscopy with biopsy was carried out. The excised tissue was also investigated microscopically and correlates to the biopsy-result. Because no different pathological changes were found, it is concluded that biopsies performed during arthroscopy of the temporomandibular joint are representative for histological investigation. An additional perforation for introducing the biopsy forceps is not necessary, because results obtained with different techniques appeared to be equally accurate. PMID- 7790510 TI - Lengthening of the hypoplastic mandible by gradual distraction in childhood--a preliminary report. AB - Uni- or bilateral mandibular hypoplasia can be associated with various syndromes or is acquired after early traumatic or inflammatory disease in the temporomandibular joint (TMJ). Early treatment is necessary to avoid consequent impairment of midfacial growth. The standard treatment of these malformations consists of the application of bone grafts which can lead to unpredictable growth. Furthermore, these procedures often require intermaxillary fixation and sometimes blood transfusions. Lengthening of the mandible by gradual distraction, according to the method of Ilizarov, opens new perspectives for interceptive therapy. This paper reports on this method applied in 9 cases of mandibular hypoplasia. Out of 3 bilateral and 6 unilateral mandibular distractions the average amount of bone lengthening was 21 mm, ranging from 15 to 25 mm. In order to facilitate ossification, the mandibles were maintained in external fixation for an average of 9 weeks subsequent to the period of active lengthening. Thereafter, immediate postoperative orthodontic treatment is necessary to avoid a relapse. No complications were noted during the follow-up period (max 17 months). PMID- 7790512 TI - Correction of post-traumatic orbital deformities: operative techniques and review of 26 patients. AB - The skeletal reconstruction of post-traumatic orbital deformities includes the zygomatic complex, the nasoethmoid area and the internal orbit. Repositioning of the malpositioned zygoma is the key element and the first step. Due to remodelling processes, most of the landmarks for proper positioning are lost, leaving the lateral orbital wall as the only reliable landmark in secondary revisions. The details of the skeletal reconstruction are discussed. Between January 1988 and December 1992, 31 patients with major post-traumatic orbital deformities have been operated on, of which 26 could be followed for a minimum of 6 months. A total of 61 operative procedures using craniofacial techniques have been performed. Complications occurred in 5 (15%) of the 26 patients, the most severe being visual loss caused by a displaced bone graft. The most frequent deformity was enophthalmos. Most patients presented with more than one deformity. The aesthetic results were rated as 'good' in 12, 'satisfactory' in 8 and 'unsatisfactory' in 6 patients. Of the patients suffering from double vision, 55% were improved after orbital reconstruction. Craniofacial techniques allow radical correction of post-traumatic skeletal deformities. The functional and aesthetic results, however, are limited by the soft tissues. PMID- 7790513 TI - Maxillofacial blast injuries. AB - Blast injuries cause specific lesions and occur more often than previously, because of the wide use of explosives. This is especially the case in wartime. More and more people lose their lives every day due to blast injuries. The mechanism of the injury and pathophysiology of this trauma are discussed. The clinical effects as well as management are presented. The most dramatic effects observed are fractures to the middle third of the face, reported here for the first time, with their management. New fracture lines are typically seen in fractures of the mandible due to the blast wave effects. This presentation should help in the prevention and management to save the lives of patients in future. PMID- 7790514 TI - Otoplasty and its origins for the correction of prominent ears. AB - The authors present a review of the literature concerning surgical correction of lop ear, re-examining the original procedures. Their own approach which combines the most suitable of several techniques described in the literature is presented. Using this approach they achieve good results stimulating them to continue utilizing this personal procedure. PMID- 7790515 TI - Back to school: training opportunities in school-based health centers. AB - School-based health centers are a rapidly growing model for provision of comprehensive, primary health care to elementary, middle, and senior high school students. They offer an exciting new training opportunity that is nontraditional, multidisciplinary, and relevant to future practice. The programs funded by the Robert Wood Johnson Foundation found that trainees made a significant contribution to their projects. The value of school-based health centers as training sites extends to trainees, schools, and the future growth of school based health centers. Integration of medical and mental health services and delivery of services by a multidisciplinary team are essential components of school-based health centers. These characteristics make school sites well suited to the training needs and practice opportunities sought by a number of disciplines, including developmental and behavioral pediatrics. A school-based health center rotation may be particularly important in developmental and behavioral pediatrics because many trainees may be called on to consult with schools in their future careers, and this rotation may provide their only school related experience. PMID- 7790516 TI - Massage therapy for infants and children. AB - Data are reviewed on the effects of massage therapy on infants and children with various medical conditions. The infants include: premature infants, cocaine exposed infants, HIV-exposed infants, infants parented by depressed mothers, and full-term infants without medical problems. The childhood conditions include: abuse (sexual and physical), asthma, autism, burns, cancer, developmental delays, dermatitis (psoriasis), diabetes, eating disorders (bulimia), juvenile rheumatoid arthritis, posttraumatic stress disorder, and psychiatric problems. Generally, the massage therapy has resulted in lower anxiety and stress hormones and improved clinical course. Having grandparent volunteers and parents give the therapy enhances their own wellness and provides a cost-effective treatment for the children. PMID- 7790517 TI - The accuracy of children's reports with anatomically correct dolls. AB - The accuracy of children's reports of alleged sexual abuse during interviews with anatomically correct dolls is the focus of considerable controversy. This study used an analog experience to measure empirically the accuracy of reports in a relevant, but controlled setting: the forensic medical examination for suspected sexual abuse. Twenty-one 3- to 7-year-old children were interviewed about what occurred during previous examinations with open-ended questions, open-ended questions with anatomically correct dolls, and direct questions with the dolls. Children provided significantly more accurate reports and fewer omissions with direct questions using the dolls compared with either of the two open-ended sections, but there was no significant difference in the number of false reports across the three sections of the interview. These results suggest that anatomically correct dolls may bolster the recall of children's memory in the setting of direct questions without prompting false reports. PMID- 7790518 TI - Head growth in cocaine-exposed infants: relationship to neonate hair level. AB - Intrauterine brain growth retardation is the most common brain abnormality in infants of cocaine-abusing mothers. We report a cross-sectional study of "at risk" pregnancies with 34 infants born to mothers urine positive for cocaine at delivery compared to 33 infants born to urine-negative mothers from the same clinic. Degree of cocaine exposure was assessed by radioimmunoassay of combined cocaine and benzoylecgonine (BE) levels in neonatal hair samples. Twenty-eight neonates were hair-positive for BE (mean 2507.40 +/- 1248.88 ng/g hair; range 716 to 5440 ng/g) and differed significantly from the control infants (n = 33) in head circumference and head growth percentiles. A negative correlation approaching significance was found between mean BE and head circumference (r = .36; p < .06) in the group of newborns with hair positive for BE (n = 28). The study demonstrates for the first time head growth abnormalities in association with levels of cocaine exposure. PMID- 7790520 TI - Effects of intraventricular hemorrhage and other medical and environmental risks on multiple outcomes at age three years. AB - This study examined the interrelated effects of intraventricular hemorrhage (IVH), neonatal medical condition, and environmental quality on development. At age 3 years, the functioning of 105 preterms was assessed in a variety of cognitive areas. Analyses revealed that IVH was related to gross motor, receptive, and expressive communication ability. However, it was only the subjects who had severe IVH who performed significantly worse than the comparison subjects. Subjects who had hemorrhages confined to a germinal matrix or a small intraventricular bleed did not differ from the comparison subjects who performed at expected age levels. When medical condition, socioeconomic status, and family risk, a composite variable including proximal environmental measures, were examined together with IVH as predictors, IVH remained related to motor and receptive communication ability after controlling for the other variables. The number of other medical complications and the environmental factors had more wide ranging effects. Each predictor was related to a unique set of outcomes. PMID- 7790521 TI - Follow-up studies of preterm infants. PMID- 7790519 TI - Self-esteem and behavior in girls with Turner syndrome. AB - Data on social competence, behavior, and self-esteem were gathered from a large sample of girls with Turner syndrome to determine whether psychological difficulties were associated with Turner syndrome. Subjects included 97 girls with Turner syndrome, 7 to 14 years of age, and 93 girls without Turner syndrome recruited from public schools. The two groups of girls were similar in age, verbal intelligence scores, and racial composition. The girls with Turner syndrome were found, based on both parental and self-report, to be more immature than the girls in the comparison group, with weaker social relationships, school performance, and self-esteem. A decline in self-esteem was also documented for the girls with Turner syndrome, but not the comparison group, as they moved into early adolescence. Although the findings support an increased risk for subtle behavioral problems among girls with Turner syndrome, in most cases the problems endorsed were not severe enough to suggest clinical impairment. PMID- 7790522 TI - Enhancing refusal skills: identifying contexts that place adolescents at risk for unwanted sexual activity. AB - Refusal skills training is one approach to reducing school-age pregnancy and sexually transmitted disease. The generalization of these skills is dependent, in part, on the relevance to participants of the training scenarios. We identified and cross-validated relevant contexts for inclusion in scenarios for refusal skills training. Fifty-six sexually active female adolescents identified 59 contexts associated with unwanted sexual activity. Fifty-one additional subjects rated these on 9-point Likert scales according to how common and difficult each was for them. Unsupervised activity where alcohol is present or feeling an obligation to engage in sexual activity emerged as high risk contexts. The most common and difficult contexts provide points of departure for the development of relevant training scenarios for refusal skills training, thereby contributing to generalization of these skills and reducing the risk of unwanted sexual activity within this population. PMID- 7790523 TI - Elimination of Elyzol 25% Dentalgel matrix from periodontal pockets. AB - Elyzo 25% Dentalgel (EDG) which is developed for use in the treatment of periodontitis is a suspension of metronidazole benzoate (40%) in a mixture of glyceryl mono-oleate (GMO) and triglyceride (sesame oil). Metronidazole can be detected in the periodontal pockets 24-36 h after application. The aim of the present study was to estimate the period of time that the gel matrix persists on periodontal pockets after 1 application of EDG. 12 patients were included in the study. From each patient, 1 sample was taken before and immediately after, and 1, 2, 3, 4, 5, 6, 8, 12 and 24 h after application. Subgingival scaling followed by absorption of gingival crevicular fluid with filter paper was used for sampling. The sampling unit was 1 tooth. Each sample was assayed for the amount of GMO and oleic acid (a degradation product of GMO) by means of high-performance liquid chromatography (HPLC) with UV detection. To allow determination of the GMO dose applied into the pockets and to estimate the recovery rate of the sampling method, 1 tooth in each patient was selected for sampling as soon as the gel had set, i.e., about 10 min after application. Only in 1 patient was a detectable amount of GMO within the pocket revealed 24 h after application. This amount was approximately 0.5% of the mean GMO dose applied around 1 tooth. GMO was found no longer than 12 h in the remaining patients. PMID- 7790525 TI - Periodontal disease activity: a development strategy for its investigation by means of accurate 3-dimensional clinical measurement. AB - The central problem in all previous approaches to clinical assessment of periodontal disease activity is the use of unidimensional measurement, which implies a number of unjustifiable assumptions. In addition, the use of unidimensional probing measurement has established that there are several distinct problems of validity and reliability in currently available techniques. The present paper begins with an analysis of these matters, leading to an approach to accurate clinical measurement of periodontitis in 3 dimensions, with the possibility of future development of a valid system for assessing the nature of disease activity. PMID- 7790524 TI - Periodontopathogens in elderly Chinese with different periodontal disease experience. AB - If an etiological relationship exists between destructive periodontal disease and putative periodontopathogens, they would be expected to have a very low prevalence in periodontally healthy elderly persons. To test this hypothesis, 2 subgroups of elderly, rural Chinese (a periodontally "best" and a "worst" group, each comprising 15 persons) were identified in 1990 from a cohort aged 55-69 years, examined in 1984. Assessment of changes in periodontal status over the 6 year period were possible by comparing detailed clinical recordings performed by the same examinator. Subgingival microbial samples were taken at the mesial aspects of an upper central incisor and a lower canine and examined for the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia group, Prevotella melaninogenica group, Capnocytophaga, Selenomonas, Campylobacter rectus as well as predominant Streptococcus and Actinomyces species. During the 6 years prior to microbiological sampling, persons in the "best" group had lost an average of 1.21 +/- 0.48 mm attachment, while persons in the "worst" group had lost an average of 1.60 +/- 0.94 mm. The latter group had lost 53.3 teeth, predominantly for periodontal reasons, in contrast to 1.8 teeth lost in the "best" group. "Best" persons did not differ from "worst" persons with respect to the occurrence of the putative periopathogens, total viable count, and total streptococcal and Actinomyces recovery. Similarly, sites which had experienced an attachment loss > or = 2 mm during the 6-year period did not differ microbiologically from sites with less attachment loss. It is concluded that subgingival microbial characterization does not allow for a distinction between elderly individuals with markedly different periodontal disease experiences. PMID- 7790526 TI - Periodontal repair in dogs: evaluation of the natural disease model. AB - Animal models are frequently consulted for histometric analysis of periodontal reconstructive therapy. Such models include surgical, periodontitis-simulating and natural disease defects in canines or non-human primates. Our studies suggest that homogeneity in defect height is critical for sensitivity of surgical and periodontitis-simulating supraalevolar defect models in discriminating treatment effects. We herein evaluate this model aspect for natural disease defects. Buccal lingual histologic sections from the 2nd, 3rd, and 4th mandibular premolar teeth (P2, P3, P4) from 6 aged beagle dogs with advanced natural periodontal disease were used. Defect heights from the reduced alveolar bone to the cemento-enamel junction were recorded in central step-serial sections at the buccal and lingual surfaces of the mesial and distal roots for the premolar teeth. Mean defect height, standard deviation and coefficient of variation were calculated for tooth types and jaw quadrants, separately, and for all teeth. Confidence intervals were calculated for teeth in left and right jaw quadrants. Mean defect height and standard deviation for left and right jaw quadrants was 3.6 +/- 0.9 and 3.3 +/- 0.6 mm for P2, 3.3 +/- 0.9 and 2.3 +/- 0.9 mm for P3, and 3.3 +/- 1.0 and 4.5 +/- 1.6 mm for P4, respectively. Coefficient of variation for defects for left and right jaw quadrants was 26 and 40%, respectively. Using confidence intervals for mean differences between jaw quadrants, it was determined that a mean treatment effect may be as large as 0.8, 1.1 and 1.9 mm for P2, P3 and P4, respectively, before being detected as statistically significant (p < or = 0.05; N = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790527 TI - Periodontal and systemic findings in children with marginal bone loss in the primary dentition. AB - In a previous population-based study of 3896 7-9-year-old children living in Sweden, it was found that 32 children (0.8%) exhibited radiographic, periodontal bone loss at > or = 2 proximal surfaces of their deciduous teeth. In the present study, 26 of the 32 children were subjected to additional oral and systemic health examination. 20 other children without any radiographic evidence of bone loss in their primary dentition served as referents. None of the cases or the referents were detected to have any systemic disease. The frequency of bleeding and suppuration on probing, radiographic proximal calculus and probing attachment loss was higher among the cases than the referents. Actinobacillus actinomycetemcomitants was found subgingivally in 14 of the cases but in none of the referents. 11 of 22 cases analysed for presence of serum antibodies against A. actinomycetemcomitans leukotoxin were sero-positive compared to none of 7 referents available for analysis. Evaluation of the data from each child revealed wide variations in clinical parameters among the children in the case group. In this group, there were children with deep probing depths, probing attachment loss, suppuration on probing, proximal calculus and presence of subgingival A. actinomycetemcomitans, indicating current periodontitis. However, in the case group there were also children without positive signs of inflammatory disease, similar to the children in the reference group. In fact, the findings suggest that less than half of the number of individuals with > or = 2 proximal sites with bone loss had current periodontitis. PMID- 7790528 TI - Lower protein concentration in GCF from patients with periodontitis: an indicator of host-specific inflammatory reaction. AB - To study the local inflammatory reaction associated with gingivitis and periodontitis, the protein concentrations were measured in gingival crevicular fluid (GCF) from 3 types of site: (i) inflamed sites in patients with gingivitis alone; (ii) inflamed sites with or (iii) without tissue destruction in patients with periodontitis. The GCF was sampled with paper strips and the protein concentration was measured with the Bradford protein assay. Higher protein concentrations in GCF were found at inflamed sites in patients with gingivitis alone than at clinically similar sites without tissue destruction in patients with periodontitis. In contrast, the sites with various degrees of disease in the same periodontitis patient showed the same protein concentrations. These discrepancies indicate that the local inflammatory reaction in the gingiva is host- and not site-specific, i.e., the tissue destruction in periodontitis reflects a specific host response. PMID- 7790529 TI - Effect of cigarette smoking on periodontal healing following GTR in infrabony defects. A preliminary retrospective study. AB - This retrospective study examined the effect of cigarette smoking on the healing response following guided tissue regeneration (GTR) in deep infrabony defects. 71 defects in 51 patients underwent GTR with teflon membranes. 20 patients (32 defects) smoked more than 10 cigarettes per day, while 31 patients (39 defects) did not smoke. Clinical measurements were available at baseline, at membrane removal and at the 1-year follow-up. The oral hygiene of both groups was good, but smokers had significantly higher full-mouth plaque scores. No significant differences were observed between smokers and non-smokers in terms of % of tissue gained at membrane removal. At the 1-year follow-up, however, smokers gained significantly less probing attachment level than non-smokers (2.1 +/- 1.2 mm compared with 5.2 +/- 1.9 mm). A multivariate model, correcting for the oral hygiene level of the patients and the depth of the infrabony component, indicated that smoking was in itself a significant factor in determining the clinical outcome. A risk-assessment analysis indicated that smokers had a significantly greater risk than non-smokers to display a reduced probing attachment level gain following GTR. It is concluded that cigarette smoking is associated with a reduced healing response after GTR treatment, and may be responsible, at least in part, for the observed results. PMID- 7790530 TI - Microscopic spirochete counts in untreated subjects with and without periodontal tissue destruction. AB - The purpose of the study was to determine microscopically the %s of spirochetes at sites without periodontal destruction in subjects with destructive periodontal diseases (cases) and in subjects free of it (controls), who had not received professional prophylaxis. From a sample of 164 individuals aged between 30-44 years living in rural and urban areas of Tanzania, cases and controls were selected. Cases (n = 25) were selected who exhibited at least 3 teeth with pocket depth of > 5 mm. The controls (n = 28) had no pockets deeper than 3 mm. From each subject, 1 subgingival plaque sample was taken at the mid point of the lingual surface of 1 of the upper premolars which showed bleeding on probing but no calculus and no pockets. In addition, one subgingival sample was obtained from a pocket. Pockets contained the highest %s of spirochetes, which confirms earlier findings. A significant difference in % of spirochetes between cases and controls was found at non-destructive sites, indicating a host effect on the subgingival microflora. However, the spirochete counts at non-destructive sites did not provide a reliable measure to identify subjects with destructive periodontal disease. PMID- 7790531 TI - Granulocyte elastase in gingival crevicular fluid: improved monitoring of the site-specific response to treatment in patients with destructive periodontitis. AB - In 13 patients with severe destructive periodontitis, the response to periodontal therapy was estimated by granulocyte elastase level in gingival crevicular fluid (GCF). 62 sites were classified according to changes of probing depths (PD) and quantitative bone height (BH%) before and after 5-year regular maintenance treatment: (i) 17 consistently healthy sites with no changes of PD and BH%; (ii) 6 initially healthy sites with deterioration in PD and BH%; (iii) 14 diseased sites with improvement in PD and BH%; (iv) 25 diseased sites with no improvement in PD and BH%. GCF was collected by an intracrevicular washing system. The released elastase in the supernatants (EA-S) and the cell-bound elastase in the pellets (EA-P) were determined with a low molecular weight substrate specific for granulocyte elastase. The ratio of EA-S and EA-P (S/P-ratio) was used as a relative measure of elastase released by the granulocytes present. The sites classified as diseased with no improvement or initially healthy but deteriorating, had significantly higher EA-S, EA-P and S/P-ratios than the consistently healthy sites or diseased but improving sites (p < 0.01). Both EA-S and S/P-ratio showed strongly positive correlations with the current levels of gingival inflammation and periodontal destruction (p < 0.001). The present study suggests that increased elastase level is associated with disease progression, and may be used to monitor the response to longitudinal maintenance therapy. PMID- 7790533 TI - Different types of inflammatory reactions in peri-implant soft tissues. AB - The aim of the present study was to analyze some features of the peri-implant mucosa at sites in the dog model which had been exposed to plaque accumulation for periods up to 9 months. The experiment was carried out in 5 labrador dogs. The mandibular right and left 2nd, 3rd and 4th premolars (2P2, 3P3, 4P4) and the 1st molars (1M1) were extracted. Following a 3-month healing period, 3 titanium fixtures (Nobelpharma AB, Goteborg, Sweden) were installed in the edentulous premolar/molar regions. Abutment connection was performed 3 months later and a meticulous plaque control period of 3 months was initiated. A clinical examination was performed at the end of this preparatory period and a main study period of 9 months continued. During this period, the plaque control regimen was maintained in the mesial and central (left: L1, 2 and right: R1, 2) implant segments, whereas plaque was allowed to accumulate on the distal implants, i.e.. L3 and R3. At the end of the main study period, i.e., 12 months after abutment connection, the clinical examination was repeated, the animals perfused and biopsies obtained. Semi-thin sections were produced for histometric and morphometric analyses. The peri-implant mucosa at implant sites exposed to daily and comprehensive plaque control at biopsy was clinically noninflamed and the connective tissue lateral to a junctional epithelium was devoid of accumulations of inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790532 TI - Role of periosteum in the formation of jaw bone. An experiment in the rat. AB - The aim of the present investigation was to evaluate the bone-forming capacity of the outer (fibrous) and inner (cambium) layer of the mandibular periosteum in skeletally mature rats. The experiment was carried out in 25 rats. The mandibular ramus was exposed on one side (experimental side) after elevation of a muscle periosteal flap. A teflon capsule was placed with its opening facing the periosteum at the subsurface of the raised muscle-periosteal flap after suturing. In the contralateral side serving as control, the periosteum of the lateral aspect of the mandibular ramus was left intact. This time the teflon capsule was placed with its opening facing the periosteum left behind at the ramus. The histological analysis demonstrated that in all experimental and control specimens, some bone was produced at 7 days after operation. In the experimental specimens, however, both the incidence and the amount of newly-formed bone in the teflon capsules gradually decreased from 7 to 120 days, while increasing in the control capsules placed over the periosteum. At 120 days, the mean amount of new bone produced in the experimental capsules was 3% (range 0-15%) of the total space created by the capsule, while it was 68% (range 41-85%) for the control capsules. The results demonstrated that substantial amounts of bone can be produced predictably by the placement of an occlusive teflon capsule facing mandibular covered with periosteum. Bone produced from the periosteum and without continuity with existing bone becomes resorbed with time. PMID- 7790534 TI - The effect of irrigation with chlorhexidine or saline on plaque vitality. AB - 24 adult patients suffering from Adult periodontitis were assigned to 4 groups: the 1st rinsed for 1 min with 0.2% chlorhexidine gluconate (CHX); the 2nd group were irrigated for 15 s with 0.2% CHX in a pulsed oral irrigator; the 3rd group rinsed for 1 min with saline and the 4th group were irrigated for 15 s with saline. Plaque vitality was measured after the 4 experimental procedures, using the method described by Netuschil et al. and scored using the method described by Rundegren et al. The results showed that a single rinse or irrigation with 0.2% CHX solution decreased the % of viable micro-organisms, but the vitality of the bacteria remained unchanged in saline groups. Statistical analysis indicated that irrigation with CHX was more effective at reducing plaque vitality than rinsing with CHX. PMID- 7790535 TI - Middle latency response in children with learning disabilities: preliminary findings. AB - The objective of this investigation was to determine if auditory middle latency responses (MLR) obtained from children with learning disabilities (LD) differ from those obtained from children without LD. Simultaneous recordings of auditory brainstem and middle latency responses were obtained in both vertex-ipsilateral (V-I) and vertex-contralateral derivations (V-C) in 22 children (11 LD and 11 normal) in the age range of eight to twelve years whose peripheral hearing was within normal limits to bilateral. The results indicate that for specific recording conditions, the latencies of middle latency responses differ significantly between children with LD and a normal group of children. PMID- 7790536 TI - Speaker-listener familiarity: parents as judges of delayed speech intelligibility. AB - It has been frequently proposed that one source of bias in intelligibility judgments is whether the judge knows the subject personally. This study attempted to describe this bias using 4 speech-delayed children (aged 4 and 7 years) with normal hearing and no significant language delay. They were audiotaped at four points during therapy over a 12-18 month period using imitation of single words derived from the Assessment of the Intelligibility of Dysarthric Speech. Parents and a group of unfamiliar adult couples served as judges. Results indicated that mothers were significantly better than all other listeners (including fathers) at identifying the words being spoken. An interaction between listener type and subject age class was also observed with the maternal advantage being much less apparent with the 2 older subjects. Results are discussed relative to the possible source of the mothers' superior performance. PMID- 7790537 TI - The effects of topic and listener familiarity on discourse variables in procedural and narrative discourse tasks. AB - This study investigated the effects of listener and topic familiarity on procedural and narrative discourse variables. Twenty-two aphasic patients (5 Broca's, 7 conduction, and 10 anomic aphasics) and 10 normal speakers served as subjects. Topic familiarity influenced discourse production in both procedural discourse and story retell situations. In procedural discourse, a greater number of optional steps were provided with familiar topics. During retelling of familiar topic stories, a greater proportion of action and resolution clauses were included. Listener familiarity affected the story retell task only. A greater percentage of subjects provided the setting when the listener was familiar. PMID- 7790538 TI - Error analysis of pronouns by normal and language-impaired children. AB - Recent research has located extraordinary weakness in specifically language impaired (SLI) children's development other than grammatical morphemes. A problem with pronoun case marking was reported to be more prevalent in SLI children than in normally developing children matched by mean length of utterance. However, results from the present study do not support that finding. Spontaneous utterances from 3 conversational contexts were generated by 3 groups of normal and SLI children and were analyzed for accuracy of pronoun usage. Third person singular pronouns were judged according to case, gender, number, person and cohesion based on their linguistic and nonlinguistic contexts. Results indicated that SLI children exhibited more total errors than their chronological peers, but not more than their language level peers. An analysis of error types indicated a similar pattern in pronoun case marking. PMID- 7790539 TI - 3D spiral CT of the tracheobronchial tree. AB - OBJECTIVE: Because of intrinsic limitations of transverse cross-sectional imaging methods, CT sometimes is insufficient for adequate evaluation of complex tracheobronchial anomalies. This article describes a complementary 3D procedure specifically dedicated to the study of the tracheobronchial tree. MATERIALS AND METHODS: The procedure combines a specific spiral CT acquisition with 2 or 4 mm collimation, 3D surface rendering of the tracheobronchial aerial content, and double obliquity multiplanar reformats directly planned on the 3D virtual object. It was performed in 11 complex cases including 3 stented benign or malignant stenoses and 2 single lung transplantations. RESULTS: Easier understanding of the tracheobronchial status was achieved in all cases. In three cases, the procedure yielded relevant diagnostic information that neither fiberoptic endoscopy nor transverse CT had provided, leading to significant modification of patient management. CONCLUSION: Three-dimensional spiral CT of the bronchial tree with secondary reformation seems suitable in clinical practice for selected cases. PMID- 7790540 TI - Diffuse pulmonary lymphangiomatosis: CT findings. AB - OBJECTIVE: Our objective was to determine and report the CT findings in patients with diffuse pulmonary lymphangiomatosis (DPL). MATERIALS AND METHODS: We retrospectively reviewed the CT findings in eight patients with pathologically proven DPL. The patients ranged in age from 3 to 35 years (mean 15 years) and included four male and four female patients. The CT scans were analyzed for type of pulmonary infiltrative process and its distribution, presence or absence of pleural fluid or thickening, and presence or absence of thoracic lymphadenopathy. RESULTS: The main abnormality seen on conventional and high resolution CT in all patients was smooth thickening of the interlobular septa and bronchovascular bundles. Seven of eight patients had patchy bilateral areas of ground-glass attenuation. All eight patients had diffuse increased attenuation of the mediastinal fat, approximating that of water, and mild bilateral perihilar infiltration. Seven of the eight had bilateral pleural effusions or smooth thickening of the pleura (or both), and two had regions of calcified pleural thickening. CONCLUSION: The constellation of CT features of DPL is distinctive and includes diffuse, smooth thickening of interlobular septa and bronchovascular bundles with extensive infiltration of the mediastinal fat and associated perihilar infiltration. Since the CT findings described are suggestive but not pathognomonic, definitive diagnosis requires lung biopsy. PMID- 7790542 TI - Congenital cystic adenomatoid malformation in adults: CT findings. AB - OBJECTIVE: Congenital cystic adenomatoid malformation (CAM) of the lung usually presents in children, although it has rarely been described in adults. The aim of this study was to review the clinical history and the CT findings in adults with pathologically proven CAM. MATERIALS AND METHODS: Seven patients between 21 and 61 years of age with pathologically proved CAM were retrospectively identified at three institutions. Thoracic CT was reviewed in all cases. RESULTS: Six patients presented with recurrent pneumonia and one patient had recurrent pneumothoraces. Five cases were classified as a Type I CAM, and two were classified as Type II CAM. The CAMs were located exclusively in the lower lobes and exerted a mass effect on adjacent lung. They appeared as multiple thin-walled complex cystic masses ranging from 4 to 12 cm in diameter. No other congenital abnormality was identified in any patient. CONCLUSION: Cystic adenomatoid malformation in adults is rare. Patients usually present with recurrent pneumonia and a thin-walled lower lobe complex cystic mass. The diagnosis should be suggested on the basis of the clinical and CT findings. PMID- 7790541 TI - CT features of pulmonary Mycobacterium avium complex infection. AB - OBJECTIVE: The purposes of this study were to describe and compare the prevalence of disease features in subjects with Mycobacterium avium complex (MAC) disease with those of Mycobacterium tuberculosis infection (MTB), to compare the abilities of CT and chest radiography to identify the features of MAC disease, and to determine if sputum positivity is related to any of the CT features of MAC disease. METHODS: Computed tomographic scans of 15 subjects with MTB and 55 subjects with MAC were reviewed by 2 observers. Sputum culture results (obtained within 1.9 +/- 2.8 days of scanning) were available in 50 of the 55 subjects with MAC. RESULTS: Bronchiectasis involving four or more lobes (often associated with centrilobular nodules) was seen only in subjects with MAC. The combination of right middle lobe and lingular bronchiectasis was seen only in MAC (p = 0.015). Thirty-one of the 34 subjects (91%) with MAC who had cavities on CT had a positive sputum culture within 3 weeks of CT, compared with 7 of 12 subjects (58%) without cavities (p = 0.001). Similarly, 36 of 42 subjects (85%) with airspace disease, but only 2 of 8 subjects (25%) without airspace disease grew mycobacteria from their sputa (p < 0.001). Sputum positivity was not associated with the presence of bronchiectasis (p = 0.156) or nodules (p = 0.377). CONCLUSION: A subgroup of patients with MAC may be distinguished from those with MTB by the presence of widespread bronchiectasis, particularly if it involves the right middle lobe and lingula. Cavities and airspace opacification on CT are associated with positive sputum cultures for MAC. PMID- 7790543 TI - Normal bronchial and pulmonary arterial diameters measured by thin section CT. AB - OBJECTIVE: We undertook this study to evaluate the normal values of the artery bronchus ratio (ABR) and the bronchial lumen ratio (BLR) at subsegmental levels and to determine whether these values can be used as objective parameters for evaluation of various diseases involving the bronchovascular trees. MATERIALS AND METHODS: We analyzed high-resolution CT of 30 patients without cardiopulmonary diseases. The CT studies were performed with 5 mm collimation at 5 mm intervals from the carina to the level of the inferior pulmonary vein and with 1.5 mm collimation at 10 mm intervals through the remainder of the lung. Both ABR, defined as the outer diameter of the pulmonary artery were divided by the outer diameter of its accompanying bronchus, and BLR, defined as the inner diameter of the bronchus divided by its outer diameter, were measured at the subsegmental level on the display console. RESULTS: The mean ABR was 0.98 +/- 0.14 (range, 0.53-1.39), and the mean BLR was 0.66 +/- 0.06 (range, 0.51-0.86). Although BLR revealed no statistical differences between segments, lobes, and lungs, there were statistically significant differences between the ABRs of segments and between those of lobes. CONCLUSION: There was a wide range of normal values of ABR and BLR. This wide range of values would make these parameters of less value in the evaluation of bronchovascular bundles. PMID- 7790545 TI - CT evaluation of mediastinal lymphadenopathy: noncontrast 5 mm vs postcontrast 10 mm sections. AB - OBJECTIVE: Two CT techniques were compared in the assessment of mediastinal lymph nodes: 5 mm thick sections without intravenous contrast medium and 10 mm thick sections with intravenous contrast medium. MATERIALS AND METHODS: Seventy-nine adult patients were examined by chest CT. From the level of the aortic arch through the level of the right middle lobe bronchus 5 mm thick sections were performed without intravenous contrast medium, followed by 10 mm thick sections of the same region with intravenous contrast medium. Two chest radiologists separately reviewed each CT method for each patient. Mediastinal lymph nodes were localized according to the American Thoracic Society scheme. Lymph node diameter was measured on the short axis. RESULTS: The 5 mm thick noncontrast sections permitted identification of more mediastinal lymph nodes than the 10 mm thick contrast enhanced sections (p < 0.01, signed rank test). The 5 mm thick unenhanced sections tended to show slightly (1-2 mm) larger nodes than the 10 mm thick contrast enhanced sections (stations 7, 10R, both reviewers, p < 0.05, signed rank test). Nodes with a short axis diameter > or = 8 mm were identified comparably well using either CT technique. CONCLUSION: The present study indicates that CT of the mediastinum using 5 mm thick sections, without intravenous contrast medium, is an appropriate scanning technique for evaluation of mediastinal lymphadenopathy. PMID- 7790544 TI - CT-guided pleural needle biopsy in the diagnosis of malignant mesothelioma. AB - OBJECTIVE: Our goal was to determine the sensitivity of CT-guided closed pleural needle biopsy (CPNB) for the histopathologic diagnosis of diffuse malignant pleural mesothelioma (DMPM). MATERIALS AND METHODS: Thirty patients with DMPM were studied with CT-guided CPNB. Tumor specimens were classified according to their cell types. RESULTS: In 25 (83.3%) patients, the diagnosis was made by CT guided CPNB. The remaining five patients were diagnosed by thoracoscopy, thoracotomy, or excisional biopsy of the chest wall mass. Pneumothorax was observed in 9.5% of patients and local seeding of tumor in 21.7% of patients who underwent CPNB. CONCLUSION: Properly performed CPNB under CT guidance may yield an increased sensitivity for the diagnosis of diffuse malignant pleural mesothelioma. PMID- 7790546 TI - CT and MR findings in tuberculous mediastinitis. AB - OBJECTIVE: Tuberculous mediastinitis, a rare complication of pulmonary tuberculosis, may simulate a mediastinal tumor on chest radiography. For evaluation and follow-up of the disease, CT and MRI are needed. MATERIALS AND METHODS: Two cases of tuberculous mediastinitis are presented with emphasis on the importance of MRI. In both cases, MRI was performed because the CT appearance was unusual for a mediastinal tumor. RESULTS: The areas of low signal intensity within the anterior mediastinal mass on both T1- and T2-weighted imaging were due to the reactive fibrous tissue and were suggestive of an inflammatory mass. CONCLUSION: When a mediastinal mass would be unusual on CT, MRI should be performed. If there are areas of low signal intensity within the mass on both T1- and T2-weighted imaging, an inflammatory mass such as tuberculous mediastinitis, is one of the possibilities. PMID- 7790547 TI - An electron-beam CT approach for transvenous coronary arteriography. AB - OBJECTIVE: The goal is to image the 3D anatomy of the major coronary arteries within a single breath-hold and using a single intravenous injection of contrast agent. MATERIALS AND METHODS: With use of an electron-beam CT (EBCT) scanner, operated in its multislice scan mode (using all four target rings, each scanning two nominal 8 mm thick slices in a total time interval of 224 ms), a radiologically realistic thorax phantom containing a heart with coronary arteries (opacified with 40 mg iodine/ml) was scanned six times with the patient table advanced by a 2 mm step into the scanner between each scan. The normalized and scaled sinogram data were transferred to an off-line computer and reconstructed using our own implementation of a 3D algebraic reconstruction technique that takes into account the exact 3D relationship of the X-ray source and detector elements of the EBCT. RESULTS: A single volume image consisting of 40 slices, at 2 mm intervals and each uniformly 3.7 mm thick, depicted the lumina of the coronary arteries with greater anatomic detail than the "original" images at 8 mm, primarily because of the reduced partial volume effect. CONCLUSION: Our preliminary results suggest that EBCT, operated in multislice scan mode, may be useful for transvenous coronary angiography performed within a single breath hold. PMID- 7790548 TI - "Acute" fat deposition in bowel wall submucosa: CT appearance. AB - OBJECTIVE: The deposition of submucosal fat in small and large bowel is known to occur in chronic processes such as inflammatory bowel disease, and has been assumed to reflect long disease duration. However, we have observed that submucosal fat deposition can occur in a short period of time. MATERIALS AND METHODS: Four patients were evaluated in whom serial CT examinations showed intramural fat deposition occurring within six months of a normal study. Confirmation of fatty deposition was made by Hounsfield unit measurement in all patients and by pathologic examination of bowel specimens in two patients. RESULTS: All four patients received cytoreductive chemotherapy for treatment of lymphoma or leukemia prior to the development of fat deposition. In all patients, serial CT examination documented the occurrence of fat-attenuation bowel wall thickening that developed in a short time period (12, 36, 67, and 186 days). Three of the four cases were initially misinterpreted as wall thickening from other causes (intussusception or colitis). Pathologic examination of bowel in the two patients with the shortest time intervals confirmed the presence of mature fat confined to the submucosa. CONCLUSION: These cases demonstrate that submucosal fat deposition in bowel wall is not limited to inflammatory bowel disease and other longstanding, chronic diseases; fatty infiltration can occur in a relatively short period of time, and is particularly likely to occur after cytoreductive therapy. PMID- 7790549 TI - Silicone-suppressed 3D MRI of the breast using rotating delivery of off-resonance excitation. AB - OBJECTIVE: A new silicone-suppressed MR technique was developed, and its efficacy in identifying free silicone and differentiating it from other breast tissues was investigated. MATERIALS AND METHODS: Silicone-suppressed MRI was performed using the RODEO (rotating delivery of excitation off-resonance) pulse sequence, which selectively eliminated signal from the narrow range of (CH3)4Si resonance. Ninety breasts in 61 patients were evaluated with both a fat-suppressed 3D MR sequence and a silicone-suppressed 3D MR sequence. RESULTS: Extracapsular free silicone and silicone injections demonstrated a unique appearance compared with normal breast tissue in all cases. Magnetic resonance identified free silicone in 26 breasts, 10 of which were confirmed pathologically or from a history of previous silicone injections. No free silicone was present on MR in 64 breasts; 8 of these were confirmed by biopsy or mastectomy as showing no evidence of free silicone. This technique was useful in evaluation of prosthesis integrity, free silicone, focal palpable or mammographic lesions, and the breast with silicone injections. CONCLUSION: Silicone-suppressed RODEO MRI of the breast can accurately identify free and intracapsular silicone and can distinguish silicone from other tissues. This provides unique information about the breast in a number of specific applications. PMID- 7790550 TI - Helical CT of the liver: evaluation of injection flow rate, mode, and scan delay with a reduced-volume contrast medium bolus. AB - OBJECTIVE: The impact of injection flow rates, mono- or biphasic injection mode, and scan delay on liver and portal vein enhancement with helical CT was evaluated. MATERIALS AND METHODS: The liver of 75 consecutive patients was examined with helical CT before and after injection of 100 ml iopromide (30 g of iodine). Patients were randomly assigned to three protocols: (1) injection flow: 2 ml/s; (2) injection flow; 4 ml/s (60 ml) + 2 ml/s (40 ml); and (3) injection flow: 4 ml/s. Scanning started 40 s after the beginning of contrast material injection. A second scan was performed 70 s after contrast agent injection in Protocol 1. RESULTS: Mean parenchymal contrast enhancement was highest with Protocol 3 (48.5 HU) followed by Protocols 2 (38.9 HU) and 1 (early: 21 HU; late: 30.7 HU), with all differences being significant (p < 0.01). Enhancement of the portal vein was significantly higher with Protocols 3 and 2 (121 and 118 HU) than with Protocol 1 (early: 64 HU; late: 75 HU). CONCLUSION: Good enhancement of the liver parenchyma and the portal vessels can be obtained with 30 g of iodine if a monophasic injection with a flow rate of 4 ml/s is used. PMID- 7790551 TI - Benign hepatocellular tumors: MRI after superparamagnetic iron oxide administration. AB - OBJECTIVE: Our goal was to describe the features of benign hepatocellular tumors on superparamagnetic iron oxide (SPIO)-enhanced MR images and to evaluate the potential role of SPIO administration in the diagnosis of these tumors. MATERIALS AND METHODS: The T1- and T2-weighted SE images were performed before and after SPIO administration in 19 patients with focal nodular hyperplasia (FNH) or adenomas. The lesions were counted and qualitatively assessed. In 32 tumors with a diameter of > 10 mm, the contrast-to-noise ratio (CNR) and the liver and tumor enhancement were calculated. RESULTS: Thirty-seven tumors were detected on MR images: 29 before and 36 after SPIO administration (p < 0.05). The SPIO-enhanced T1-weighted images provided the highest detection rate and CNR. The central scar was most conspicuous on SPIO-enhanced T2-weighted images. Most FNHs and adenomas lost less signal than the liver, three tumors did not lose signal, and four FNHs showed a signal loss equal to or greater than that of the liver. CONCLUSION: The SPIO-enhanced T1-weighted images increased the CNR and the detection rate of benign hepatocellular tumors. On T2-weighted images, most benign hepatocellular tumors showed a signal decrease after SPIO administration. No significant difference in signal loss was observed between FNH and adenomas. PMID- 7790552 TI - Peribiliary cysts in liver cirrhosis: US, CT, and MR findings. AB - OBJECTIVE: We report the imaging features of hepatic peribiliary cysts (PC) and the course of their development on CT. MATERIALS AND METHODS: Both CT and US findings were correlated with histopathologic findings in two patients with PC at autopsy. Five patients with cysts around the portal vein on CT but without histologic correlation were also included in this study. In six patients the course of PC development was observed. RESULTS: In the two autopsy cases cystic dilatation of the peribiliary glands was confirmed. The cases showed continuous small cysts along the portal veins reflecting the periportal collar seen on CT and the abnormal MR signal intensity of the periportal area. Ultrasound (US) showed round or tubular anechoic lesions around the large portal tracts mimicking dilatation of the bile ducts. Clustered cysts and echogenic dots or bands around PC were also seen. In three of six cases the PCs gradually enlarged and increased in number. CONCLUSION: In patients with liver cirrhosis PCs can be demonstrated by CT, US, and MRI in the vicinity of the hepatic hilum. Peribiliary cysts enlarge gradually and must be differentiated from dilatation of bile ducts or edema of portal tracts. PMID- 7790553 TI - Liver perfusion studied with ultrafast CT. AB - OBJECTIVE: Our goal was to quantify absolute hepatic arterial and portal venous perfusion noninvasively in patients with and without liver disease using ultrafast CT. MATERIALS AND METHODS: A single slice through the porta hepatis was repeatedly scanned after bolus injection of 25 ml of iohexol 300 mg I/ml, followed by a 25 ml saline "chaser" intravenously at 10 ml/s. Thirty-nine controls, 7 cirrhotic patients, and 5 patients with known metastases on the slice plane were studied; hepatic arterial perfusion was determined in 41 patients and portal venous perfusion in 24. Time-attenuation curves from regions of interest drawn over the liver, spleen, aorta, and portal vein were analysed. Hepatic arterial perfusion was calculated by dividing the peak gradient of the liver time attenuation curve prior to the time of peak splenic attenuation by the peak aortic CT number increase. Splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT number increase. Portal perfusion was derived by scaling the splenic time-attenuation curve by the ratio of hepatic arterial/splenic perfusion. This scaled curve was subtracted from the liver time-attenuation curve to give a portal curve. The peak up-slope of this curve was divided by the peak rise in splenic or portal vein density. RESULTS: Hepatic arterial perfusion averaged 0.19 ml/min/ml (n = 31) in controls and was raised in cirrhosis to 0.25 ml/min/ml (n = 6) and metastases 0.43 ml/min/ml (n = 4). Portal venous perfusion was 0.93 ml/min/ml (n = 19) in controls and 0.43 ml/min/ml (n = 4) in cirrhosis. Reproducibility has been confirmed. CONCLUSION: Dynamic ultrafast CT shows potential in quantifying arterial and portal hepatic perfusion. The technique may be adaptable to dynamic bolus MRI. PMID- 7790555 TI - Pyourachus: CT manifestations. AB - OBJECTIVE: To assess CT findings of pyourachus. MATERIALS AND METHODS: Computed tomography of two patients with surgically proven pyourachus was reviewed. RESULTS: The CT characteristics of pyourachus include (a) midline location deep to the rectus abdominis muscle; (b) conical shape extending from a tip at the umbilicus to a base over the bladder dome; (c) peripheral inflammatory changes in subcutaneous tissues, rectus abdominis muscle, and mesenteric fat; and (d) intraperitoneal fluid or abscess (if perforation has occurred). CONCLUSION: Abdominal CT demonstrates characteristic findings in pyourachus that should allow differentiation from other abdominal-pelvic masses. PMID- 7790554 TI - Percutaneous CT-guided biopsy of adrenal masses: immediate and delayed complications. AB - OBJECTIVE: To determine the immediate and delayed complications of percutaneous adrenal biopsy and any relationship between biopsy methods and complications. MATERIALS AND METHODS: Medical records and radiological examinations of 83 percutaneous adrenal biopsy were reviewed. Indication for biopsy, inpatient/outpatient status, lesion size and location, imaging modality used, needle type, size, approach and number of passes, biopsy results, immediate complications, and delayed complications were recorded. RESULTS: Computed tomography was used in 79 cases (95%) and ultrasound in 4 (5%). The biopsy approach was posterior in 37 cases, transhepatic in 33, transpancreatic in 9, anterior in 2, transsplenic in 1, and lateral in 1. The total complication rate was 8.4% and was slightly higher for the transhepatic approach (12%) than the posterior approach (8%). Seven complications occurred: two pneumothoraces, two pain, one perinephric hemorrhage, one subcapsular and intrahepatic hematoma, and one hepatic needle-tract metastasis. The posterior approach was complicated by the two pneumothoraces and perinephric blood; the transhepatic was used in the other four. Five of the complications occurred with 22 gauge needles. CONCLUSION: Percutaneous adrenal biopsy is a safe procedure. Complications occurred in 7 of our patients (8.4%). PMID- 7790556 TI - MRI of placental polyps. AB - OBJECTIVE: Placental polyp is intrauterine polypoid placental tissue retained after delivery or abortion and may cause life-threatening bleeding. We studied the value of MRI in diagnosing placental polyps. MATERIAL AND METHODS: Two women, 26 and 32 years old, with histologically proven placental polyp were included in this study. These patients were treated with local injections of methotrexate or transcatheter arterial embolization. The MR images before and after these treatments were studied retrospectively. RESULTS: High intensity pedunculated masses of 3-4 cm in size were observed in the expanded uterine cavity on T2 weighted and contrast-enhanced T1-weighted SE images. Bloody contents were observed around the masses. Placental polyps were more intensely enhanced than the myometrium by the contrast media, and the enhanced T1-weighted images indicated the retained placental tissues with an adherent part to the myometrium. Magnetic resonance imaging was also useful in following up the reduction in the size of the lesions and in the blood flow after the treatments. CONCLUSIONS: Magnetic resonance imaging may be useful in diagnosing and following up placental polyps. PMID- 7790557 TI - Assessment of popliteal arterial occlusive disease with 2D time-of-flight MRA. AB - OBJECTIVE: The purpose of this study was to evaluate both morphology and blood flow in peripheral arteries with occlusive lesions using MR angiography (MRA) and velocity-encoded cine MRI. MATERIALS AND METHODS: Two-dimensional time-of-flight MRA and velocity-encoded cine MRI were performed in nine patients with peripheral arterial occlusive disease. Findings on MR angiograms were verified by conventional angiography. RESULTS: All the stenotic lesions in the popliteal arteries were depicted by MRA. The degree of the stenoses in the artery was overestimated by MRA. Major collateral circulations were demonstrated. Velocity encoded cine MRI provided flow velocity information on the arteries above and below the stenoses. The flow velocity waveform was monophasic above and below the stenosis. The peak systolic velocity in the artery below the stenosis was reduced compared with that above the stenosis (p < 0.05). CONCLUSION: The combination of MRA and velocity-encoded cine MRI has clinical potential for the evaluation of peripheral arterial occlusive disease. PMID- 7790558 TI - Involvement of muscle by malignant lymphoma: MR and CT appearances. AB - OBJECTIVE: The purpose of this study is to investigate the CT and MR findings of muscular involvement by malignant lymphoma and identify the CT and MR features that may assist in their diagnosis. MATERIALS AND METHODS: Magnetic resonance imaging was performed on four patients (five lesions) with pathologically proven non-Hodgkin lymphoma using a 1.5 T unit (Cases 1, 2, and 4) and a 0.5 T scanner (Case 3). Computed tomography scans were carried out on three patients (Cases 1, 3, and 4). RESULTS: The lesions that extended along muscle fascicles with preserved fat planes looking like swelling of the muscle were of slightly hyper- to isointensity relative to uninvolved muscles on T1-weighted images, of hyperintensity on T2-weighted images, and of low or isodensity on CT. Microscopically, lymphoma cells were seen clustering among normal and atrophic muscle fibers in a biopsy specimen of one patient. The lesions enhanced relatively homogeneously after Gd-DTPA injection. In three cases, vessels were coursing through the lesion on MRI and in two cases on enhanced CT. CONCLUSION: Magnetic resonance imaging proved useful to show the extension of involvement of muscular lymphoma compared with CT. The diagnosis of infiltration of muscle by lymphoma is entertained when a lesion of relatively homogeneous intensity and density extends along the muscle fascisles without obliteration of the fat planes and especially when vessels are identified within the lesion. PMID- 7790560 TI - Influence of magnetic field strength on T2* decay and phase effects in gradient echo MRI of vertebral bone marrow. AB - OBJECTIVE: The goal of this study was twofold: first, to quantify the influence of magnetic field strength (B0) on T2* and T2susceptibility relaxation rates in vertebral bone marrow; and second, to determine the significance of in-phase/out of-phase phenomena in GE MRI as a function of TEs at different B0 values. MATERIALS AND METHODS: Magnetic resonance imaging of the spine was performed at 1.5, 1.0, and 0.2 T using a GE sequence (2D-FLASH) with variable TE. Vertebral body signal intensities were measured and plotted against TE values. These curves were used to calculate T2* decay of bone marrow at different B0 values. RESULTS: At all field strengths, we observed exponential signal decay, modulated by a cosine function, the periodicity of which was proportional to B0. The T2* values of vertebral bodies were 9.7 +/- 1.8 ms at 1.5 T, 17.2 +/- 2.4 ms at 1.0 T, and 53 +/- 5 ms at 0.2 T. True T2 relaxation time (independent of field strength) was 62 +/- 4 ms. The T2susceptibility was 11.7 ms at 1.5 T, 24.8 ms at 1.0 T, and 585 ms at 0.2 T. CONCLUSION: We conclude that at low B0, susceptibility effects become less important and T2* approaches true T2 relaxation. PMID- 7790559 TI - MR findings in peroneal tendonopathy. AB - OBJECTIVE: The purpose of this presentation is to familiarize the reader with the often subtle findings of peroneal tendon derangement on MRI examination. MATERIALS AND METHODS: We present four patients who were studied with MR (1.5 T) prior to surgical exploration of the peroneal tunnel. All patients had lateral ankle symptoms for > 6 months. Normal MR anatomy and an example of the peroneus quartus tendon are also shown. RESULTS: Surgery revealed two peroneus brevis and three peroneus longus lesions. A "multipartite" appearance of the peroneus tendon on axial MR images, especially when paired with a "flame-shaped" appearance on more distal axial images, indicates a longitudinal tendon split. Both patients with peroneus brevis tendon splits had insufficient superior peroneal retinacula. CONCLUSION: Partial ruptures of the peroneal tendons characteristically take the form of longitudinal tendon splits. Axial MR images through the ankle and hindfoot can help distinguish peroneal tendonitis from longitudinal tendon splits. PMID- 7790561 TI - Relationships between young modulus of elasticity, ash density, and MRI derived effective transverse relaxation T2* in tibial specimens. AB - OBJECTIVE: It has been hypothesized that the MR relaxation time T2* of bone marrow present in the intertrabecular spaces may be related to the density of the trabecular network and may be a predictor of trabecular bone properties. MATERIALS AND METHODS: To derive a relationship between the marrow relaxation time T2* and biomechanical properties of trabecular bone, we studied two sets of trabecular bone specimens from human tibiae. The first set consisted of 12 specimens that were defatted and immersed in saline; the second set consisted of 18 specimens with marrow in the trabecular spaces. The MR studies were conducted on a 1.5 T imaging system. In the first set of specimens, a GE sequence (TR = 70 ms; TE = 5, 10, 15, 20, 25 ms) was used to obtain images in the axial plane. In the second set, a water suppression pulse was used prior to an asymmetric SE sequence (TR = 300 ms; TE = 4, 8, 12, 16, 20, 24 ms) to obtain images in the axial, coronal, and sagittal planes. The T2* of the intertrabecular saline of the marrow fat was calculated assuming a monoexponential decay. In both sets, the elastic moduli were measured in three orthogonal directions (superoinferior, anteroposterior, and mediolateral). The ash density was determined after the completion of the experiments. RESULTS: Our results indicate a moderate significant negative correlation between T2* and ash density or elastic modulus (E) in both sets of specimens. The correlation coefficients were slightly improved between the transverse relaxation rate 1/T2* and bone density or E. We found a good correlation between T2* and the reciprocal ash density (r = 0.88) and between T2* and the reciprocal elastic modulus 1/E (r = 0.87 to r = 0.95) in the first set, while in the second set the correlation remained moderate. With use of a multiple linear regression model (1/E = a x T2* + b x 1/T2* + n), the reciprocal elastic moduli 1/E were predicted to > 90% by T2* and 1/T2* in the first set of specimens. This finding was not replicated with the second set of specimens. In the second set of specimens, we found poor to moderate correlation coefficients between the T2* times in the three orthogonal planes (r = 0.45 to r = 0.71). CONCLUSION: Trabecular bone properties such as density and strength may potentially be assessed with quantitative MR techniques. However, especially for in vitro studies, specimen preparation, acquisition parameters, and specimen geometry may have a significant impact on the obtained results. PMID- 7790563 TI - MRI in acute hemiplegia of childhood. AB - OBJECTIVE: Acute hemiplegia in childhood is rare, the underlying etiology frequently obscured and the pathological site unidentified. MATERIALS AND METHODS: Magnetic resonance imaging (1.5 T Magnetom) was performed in two cases with hemiplegia followed by repeated studies at 3 and 16 months, respectively, after the initial examinations, including CT and angiography, were negative. RESULTS: MRI demonstrated otherwise occult lesions in the brain stem and showed the subsequent partial resolution consistent with infarction. CONCLUSION: MRI should be employed in those children with acute hemiplegia in whom no underlying cause is elicited. PMID- 7790562 TI - Added value of automated clinical proton MR spectroscopy of the brain. AB - OBJECTIVE: A trial was conducted to establish the added diagnostic value of an automated proton MR spectroscopy (MRS) examination (PROBE). MATERIALS AND METHODS: The PROBE and MRS were compared for metabolite ratios of normal controls and 21 patients. In addition, PROBE was performed in either the occipital cortex (gray matter) or the parietal cortex (white matter) or, more rarely, within the confines of a focal lesion identified on MRI, using a GE Signa 1.5 T whole-body scanner, in 112 patients undergoing routine brain MRI. The trial was conducted in three different MR centers to establish percentage of positive findings with MRI vs. MRI plus MRS. RESULTS: Cerebral metabolite ratios (N acetylaspartate/creatine, choline/creatine, myo-inositol/creatine) obtained by PROBE and MRS were similar. Metabolite profiles in dementia, head trauma, herpes encephalitis, hepatic and hypoxic encephalopathy, stroke, and tumor were identified using PROBE. The PROBE technique increased the number of positive findings ("added value") achieved by MRI; the added value was 28, 21, and 93% for the three trial sites. CONCLUSION: With only minor variations, PROBE reproduces the cerebral metabolite patterns obtained with MRS. It significantly increases the diagnostic yield of routine neuroimaging and might be incorporated as a standard sequence in a cost-effective manner. PMID- 7790564 TI - MR angiography of the persistent trigeminal artery variant. AB - OBJECTIVE: To evaluate the MR angiographic findings of the persistent trigeminal artery variant (PTAV) and to discuss its clinical implications. MATERIALS AND METHODS: We reviewed time-of-flight MR angiography including individual source imaging in three patients with PTAV, which had been recognized as an incidental finding on conventional arteriography. In all cases, MR angiography was performed at 1.5 T. RESULTS: MR angiography demonstrated the PTAVs as hyperintense structures originating from the precavernous portion of the internal carotid artery, running within or very close to the Meckel cave and near the trigeminal nerve root, and reaching the posterior fossa (cerebellar arteries) without joining the basilar artery. Spin echo imaging failed to demonstrate the PTAVs. CONCLUSION: Source imaging of MR angiography helped demonstrate PTAV and its adjacent structure. Knowledge of the presence and course of this anomalous vessel is useful for various treatment strategies. PMID- 7790566 TI - Fluid attenuated inversion recovery (FLAIR) MRI of herpes encephalitis. PMID- 7790565 TI - CT and MRI of hepatic focal nodular hyperplasia with peripheral steatosis. AB - Focal nodular hyperplasia (FNH) is a benign liver condition, which generally does not contain fat. In this report we describe an unusual case in which multiple areas of FNH were surrounded by prominent peripheral fatty infiltration. PMID- 7790567 TI - Oculomotor nerve invasion by lymphoma demonstrated by MRI. PMID- 7790568 TI - Incidental MR diagnosis of retractile testis. PMID- 7790569 TI - Demonstration of columella-like stapes by CT. PMID- 7790570 TI - Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. AB - The inhibitory activity of angiotensin I-converting enzyme in milk increased during fermentation with the Calpis sour milk starter containing Lactobacillus helveticus and Saccharomyces cerevisiae. Two kinds of peptides inhibitory to angiotensin I-converting enzyme were purified from the sour milk by using four step HPLC. The amino acid sequences of these inhibitors were identified as Val Pro-Pro and Ile-Pro-Pro. The concentrations of peptides providing 50% inhibition of angiotensin I-converting enzyme were 9 and 5 microM, respectively. Most of the inhibitory activity in sour milk was attributed to these two peptides. PMID- 7790573 TI - Ornithine-delta-aminotransferase in lactating bovine mammary glands. AB - The occurrence and subcellular distribution of ornithine-delta-aminotransferase have been studied in lactating bovine mammary glands. The enzyme is localized in the mitochondria and has a unique thermal reaction profile that distinguishes it from putative liver and kidney isozymes. The enzyme concentration in the gland correlates well with a role in the conversion of ornithine into the proline precursor, L-delta 1-pyrroline-5-carboxylate. However, an unusually high Michaelis constant for the mitochondrial enzyme (8.4 mM) raises the question of enzyme efficiency in vivo such that this pathway needs to be considered in estimating barriers to protein secretion into milk. PMID- 7790571 TI - Alteration of plasma lipids in the rat by fractionation of modified milk fat (butterfat). AB - Our objective was to determine the nutritional effects of defined fat fractions of modified milk fat, or butterfat (anhydrous butter without the milk fat globule membrane) on lipid and lipoprotein cholesterol concentrations in plasma of rats fed diets containing 16% fat and two amounts of cholesterol. Five dietary fats were compared: 1) intact butterfat, 2) a liquid butterfat fraction enriched in oleic acid and unsaturated triacylglycerols with < 40 carbon atoms, 3) a solid butterfat fraction enriched in palmitic and stearic acids, 4) corn oil, and 5) palm oil. The extent of diet-induced hypercholesterolemia was the greatest with palm oil, followed by solid butterfat, corn oil, intact butterfat, and the lowest with liquid butterfat. Triacylglycerol concentrations in plasma were greater for rats fed palm oil than for those fed corn oil or liquid or intact butterfat. Among the high cholesterol dietary groups, ingestion of the liquid butterfat diet resulted in similar lipoprotein cholesterol and very low density lipoprotein concentrations relative to the corn oil diet, and ingestion of the solid butterfat diet resulted in similar lipoprotein cholesterol and very low density lipoprotein concentrations relative to the palm oil diet. These results suggest that changes in the triacylglycerol and fatty acid composition of butterfat by fractionation processes may improve its nutritional profile. PMID- 7790572 TI - Role of insulin in the regulation of mammary synthesis of fat and protein. AB - Five lactating Holstein cows were subjected to a hyperinsulinemiceuglycemic clamp to examine the effects of insulin on milk yield and composition. Of special interest was the evaluation of the glucogenic-insulin theory of milk fat depression. Cows were fed every other hour to minimize postprandial effects, and blood samples were obtained via an indwelling jugular catheter every 4 h for 2 d to establish baseline glucose concentrations. For the 4-d clamp, insulin was infused continuously (1 microgram/kg of BW per h) into the contralateral jugular vein, and circulating insulin was increased approximately fivefold. Blood was sampled frequently, and blood glucose was maintained within 10% of baseline concentrations by infusion of exogenous glucose at variable rates (mean = .15 g/kg of BW per h). Dietary intake declined on the 4th d of the insulin clamp (23.0 vs. 16.3 kg/d). Milk yield, however, did not change (32.4 vs. 33.6 kg/d) in support of the lack of sensitivity of the mammary gland to insulin. Milk fat percentage (3.85 vs. 3.66) and yield (1.26 vs. 1.22 kg/d) did not change during the insulin clamp. Milk protein yield increased (.98 vs. 1.05 kg/d), and milk protein percentage tended to increase (3.04 vs. 3.14), during the insulin clamp. This modest increase in milk protein yield may have been constrained by a lack of available amino acids, as indicated by a decrease in circulating concentrations of essential amino acids, urea nitrogen, and plasma proteins. Overall, results offer no support for the glucogenic-insulin theory of milk fat depression but do indicate that the insulin infusion, either directly or indirectly, enhanced secretion of milk protein. PMID- 7790574 TI - Factors affecting variation of udder traits of dairy ewes. AB - Udder depth, width, and circumference; cistern height; teat position, angle, length, and width; and milk yield at 120 d were studied in 113 Churra sheep from three flocks. Means were 9.30, 12.18, and 46.55 cm, respectively, for udder depth, width, and circumference; 1.48 cm for cistern height; 3.64 (scored from 1 to 5) for teat position; 50.39 degrees for teat angle; 3.83 and 1.93 cm, respectively, for teat length and width; and 132.39 L for milk yield. Analysis of variance showed significant effects for lactation month, flock, parity number, and milk yield. The traits related to udder size (depth, width, and circumference) were significantly influenced by lactation month, flock, and milk yield and showed low repeatability (.17 to .18). The traits related to cistern morphology (cistern height, teat position, and angle) were significantly influenced by flock and parity number. These traits, together with teat length and width, had high repeatabilities (.45 to .77). Cistern height, teat position and angle, and size of teats are related to aptitude of the udder for mechanical milking. This association, as with cattle, would justify focusing genetic improvement on these traits. PMID- 7790575 TI - Infection of lactating goats by mammary instillation of cell-borne caprine arthritis-encephalitis virus. AB - The possibility of transmission of caprine arthritis-encephalitis virus between lactating goats by the transfer of infected cells during milking has been examined experimentally. Four virus-free Saanen goats were infected, two in full lactation and two during the drying off period, by instillation of infected allogeneic cells into the milk canal of one-half of the udder. All four goats became infected, as shown by the isolation of virus from peripheral blood monocytes, seroconversion, and presence of typical lesions in the mammary gland. The virus was rapidly and constantly demonstrable in cells from the mammary secretions of the dry goats, but less regularly detected from milk cells from the lactating goats. Virus was more frequently isolated when milk SCC were elevated. Virus was present as often in secretions from the uninoculated half of the udder as the inoculated half. Dry goats seroconverted progressively, although antibody concentrations remained low; the lactating goats developed weak, positive Western blots in the late phase of lactation but only gave positive ELISA titers after drying off and artificial reinduction of lactation. At necropsy, lesions typical of the virus were observed in the mammary tissues of all four goats, and three had arthritis of the carpi. PMID- 7790576 TI - Comparison of calf housing types and tympanic temperature rhythms in Holstein calves. AB - During fall, 30 Holstein calves were randomly assigned to three housing treatments from birth to weaning: conventional wooden hutches, enclosed molded polyethylene domes, and thermomolded opaque polymer hutches with ridge-top ventilation systems. The wooden and polymer hutches had outdoor pens. Fifteen calves, 5 in each housing type, were fitted with portable data loggers to record ambient (calf microclimate) and tympanic temperatures. Additional data collected included weekly girth, BW, and feed intake; blood samples were collected within 24 h of birth and at weaning (8 wk); and behavioral observations were made at 1, 4, and 7 wk of age. Polyethylene domes had the warmest microclimate, followed by wooden and polymer hutches. Feed intake, growth measurements, blood physiology, and behavior were unaffected by housing type. Diurnal tympanic temperature rhythms of neonatal dairy calves in this study were monophasic: maximums were at 1200 to 1700 h, and minimums were at 0600 to 0900 h. Computed fractal dimensions of tympanic temperature by week indicated a gradual diminishing of stress as the calves became older and acclimated to their environment. This objective characterization provides a basis for further evaluation of physiological stress and a means of improving environmental management. PMID- 7790580 TI - Addition of soybean trypsin inhibitor to bovine colostrum: effects on serum immunoglobulin concentrations in Jersey calves. AB - Secretion of trypsin by the neonate may reduce absorption of Ig from colostrum and increase failure of transfer of passive immunity, particularly for calves fed after 12 h of age. Jersey calves (n = 48) were used in a 2 x 2 factorial arrangement of soybean trypsin inhibitor (0 or 1 g) added to 1 L of maternal colostrum at the first two feedings and time of initial feeding (.65 or 12 h of age). A second colostrum feeding was offered 12 h after the initial feeding. Maternal colostrum was analyzed for Ig by radial immunodiffusion and trypsin inhibitor by radial protease diffusion. Jugular blood was sampled at 0, 12, 24, and 48 h after initial feeding, and serum was analyzed for IgG and IgM. Addition of trypsin inhibitor increased serum Ig and total serum protein concentrations, regardless of age at first feeding. Concentrations of serum IgG and IgM were increased 16 and 30%, respectively, when trypsin inhibitor was fed. Age of first feeding did not affect concentrations of IgG or IgM in serum. Supplementation of colostrum with trypsin inhibitor improved transfer of passive immunity to neonatal Jersey calves. PMID- 7790578 TI - Prediction of milk fatty acid profile in dairy cows fed dietary fat differing in fatty acid composition. AB - The objective of this work was to predict changes in milk fat composition caused by differences in dietary fat. Twenty-two references describing 35 experiments and 108 treatments were used in the analysis. For lauric, myristic, and palmitic acids in milk, proportions in the dietary fat and the total dietary fat concentration were important predictors for their concentrations in milk as well as for stearic and oleic acids in milk. Using a model that included these four parameters, the residual standard deviation around the observed versus predicted line within experiments was approximately 10% of the mean for short-chain fatty acids (< C12); for lauric, myristic, palmitic, and oleic acid; and for total C18 fatty acids in milk. The model also effectively predicted milk fatty acid profile with respect to lauric, myristic, palmitic, and oleic acid and total C18 fatty acids across experiments despite differences in breed, basal diet, and milk yield among experiments. The content of short-chain acids, stearic acid, and poly unsaturated fatty acids were less effectively predicted across experiments. Possible explanations for the differing predictabilities for different milk fatty acids are discussed. PMID- 7790579 TI - Sucrose supplementation and feed intake of dairy cows in early lactation. AB - Based on results from previous 14-d sequential elimination trials, which indicated that cows in early lactation preferred a sucrose-sweetened diet, a 12 wk lactation trial was conducted to evaluate further the effects of sucrose supplementation. Twenty-four cows (16 multiparous Jerseys and 8 primiparous Holsteins) were assigned at parturition to a control or sucrose-sweetened (1.5% of dietary DM) TMR in a randomized complete block design. The diet included 10% corn silage, 30% alfalfa haylage, and 60% concentrate based on corn and soybean meal on a DM basis and was fed to ensure 10% orts. An additional 2.3 kg of alfalfa hay were fed for the first 5 d postpartum. Covariant-adjusted (BW on the day of parturition) mean DMI, milk yields, 3.5% FCM yields, and percentages of milk fat, milk protein, and SNF were unaffected by treatment and averaged 19.0 and 19.1 kg/d, 28.4 and 29.3 kg/d, 28.4 and 28.4 kg/d, and 3.40 and 3.30%, 3.51 and 3.28%, and 8.4 and 8.3%, respectively, for cows on control and sucrose supplemented diets. In the absence of a choice of diets, sucrose at 1.5% of dietary DM did not enhance mean DMI over the first 12 wk postpartum; however, a transient increase in consumption of the sucrose-supplemented diet may have occurred over the a 2-wk period after parturition. Variation in feed consumption during early lactation suggests that additional data are needed to examine this potential effect. PMID- 7790577 TI - Effect of supplemental dietary fat or protein on the short-term milk production response to bovine somatotropin. AB - Effects of supplemental energy or protein on the milk production response to bST administration were examined in two separate trials. In trial 1, 40 cows were used in a 2 x 2 factorial, completely randomized design to determine the effects of bST and fat supplementation. The study consisted of a 7-d pretreatment period and a 42-d treatment period. Fat was top-dressed at 3.0 Mcal/d of NEL, and bST was administered. Supplemental fat had no effect on milk production, and NEL intakes were unaffected. Administration of bST increased milk production by 7.1 kg/d, and the milk production response was unaffected by supplemental fat. In trial 2, 4 cows were used in four periods with a 2 x 2 factorial arrangement in which water or casein was infused into the abomasum of cows fed for ad libitum intake or at 80% of their requirements. Diets and infusions were initiated simultaneously and continued for 11 d. All cows were given bST during the last 5 d. Infusion of water or casein did not alter the milk production response to bST, but restricted feeding reduced the bST response (3.2 vs. 7.2 kg/d). Concentrations of IGF-I in plasma were increased by bST administration, and the increase was greatest for cows fed for ad libitum intake. The milk production response to bST was not increased by additional energy or protein offered to cows fed well-balanced diets. PMID- 7790581 TI - Effects of housing and colostrum feeding on serum immunoglobulins, growth, and fecal scores of Jersey calves. AB - Ninety-six Jersey calves were used to evaluate the effects of housing and method of colostrum feeding on serum Ig concentrations, incidence and severity of scours, intake, and BW changes from birth to 35 d of age. Calves were separated from the dam and fed 2 L of colostrum in nipple-bottles or allowed to nurse the dam for 3 d. Calves were housed in individual hutches or wooden pens in a barn. Intake of colostrum by calves allowed to nurse the dam was not controlled. Serum IgG and IgM concentrations at 24 h of age were greater for calves that nursed the dam. Scours were less severe when calves were housed in hutches, but number of days scouring was unaffected by treatment. Calves fed colostrum in nipple-bottles and housed in the barn consumed more starter than did other calves from 3 to 5 wk of age. The BW were greater for calves allowed to nurse the dam and housed in hutches. Feed efficiency over the 35-d study was improved when calves nursed the dam. Optimal transfer of passive immunity and housing in hutches appeared to maximize health and growth in this study. PMID- 7790582 TI - Plasma proteins and a probiotic as ingredients in milk replacer. AB - Milk replacers containing all milk protein, 25% of protein from porcine plasma protein, 25% of protein from bovine plasma protein, or all milk protein plus probiotic were compared in a 6-wk experiment using 120 Holstein bull calves approximately 7 d of age. All replacers contained an antibiotic except the one that contained probiotic. Calf starter always was available, and calves were weaned when they consumed 680 g/d of starter. Ten calves were selected randomly from each group for sampling of jugular blood at d 1 and 10 of the experiment. A complete blood count was conducted on the samples, and protein fractionation by electrophoresis was performed on sera harvested from the samples. Mean BW gains started to differ at the end of wk 3, and by the end of wk 6 the difference of 2.6 kg was significantly greater for those calves fed porcine or bovine plasma than for calves fed all milk protein (with or without probiotic). The same response was noted for starter consumption; the difference increased to 4.15 kg by the end of wk 6. Most measurements of blood did not differ by treatment; those that were different did not suggest an apparent difference in performance response. Growth performance of calves fed probiotic was not different from that of calves fed antibiotic when both replacers contained all milk protein. Either porcine or bovine plasma protein was an acceptable source of protein. PMID- 7790584 TI - Correlations among somatic cell scores of milk within and across lactations and linear type traits of Jerseys. AB - Genetic and phenotypic correlations were estimated for means of log2 SCC (somatic cell scores) from the first 305 d, the first 75 d, the first 150 d, 76 to 305 d, and 151 to 305 d of lactation for first and second lactations using REML. Somatic cell scores from the Dairy Records Processing Center in Raleigh, North Carolina for 31,180 Jersey cows sired by 411 bulls were used for analyses. Correlations between sire evaluations for somatic cell scores from this study and linear type traits from the American Jersey Cattle Club were also calculated. The model used for analyses of the somatic cell score means included herd-year of calving, age at first calving, sire, and residual. Heritability estimates for the means ranged from .05 to .15 (.12 for 305-d mean for first lactation). Genetic correlations among the somatic cell score means within first and within second lactation were > or = .79. The genetic correlation between the 305-d mean from first and second lactation was .90. The smallest genetic correlation across lactations was .68. Somatic cell scores measured at various times were under similar genetic control. Phenotypic correlations were usually much smaller than genetic correlations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790583 TI - Association of alleles for the class I bovine lymphocyte antigens with conformation, semen traits, and growth rate of young bulls. AB - The 279 Norwegian bulls that were performance tested during 1988 and 1989 were typed for bovine lymphocyte antigens of class I, and relationships with performance test results of these bulls were investigated. A single-trait animal model was used to estimate the gene substitution effects of bovine lymphocyte antigens on conformation as well as semen volume, density, and quality; a fixed linear model was also applied to the breeding values of growth rate. Allelic frequencies ranged from .2 to 28%; alleles w16 (28%), A2 (15%), A10(w50) (12%), and A8 (10%) were the most frequent. Allele A12(A30) was significantly associated with decreased semen density and decreased growth rate, and allele A10(w50) was significantly associated with increased growth rate. No antigen showed a significant association with conformation, semen density, or semen quality. Heterozygosity at the locus for bovine lymphocyte antigen of class I did not show significant advantage in any of the traits. The bovine lymphocyte antigens appeared to be potential markers for quantitative trait loci controlling semen density and growth rate; however, further research is necessary to confirm these findings. PMID- 7790586 TI - The effect of test day models on the estimation of genetic parameters and breeding values for dairy yield traits. AB - The present study estimated genetic parameters for yields of milk, fat, and protein applying REML procedures under test day animal models. The data consisted of 155,494 test day records from 15,756 Friesian cows in first lactation from one region in northern Germany. The models applied included a traditional herd-year season model for the analysis of single test days and 305-d records and two test day models differing by the definition of contemporary groups, either as herd year-season of calving or as herd-test day. For single test days, heritabilities were highest for midlactation yields. For test day models, estimates of heritability varied with the number of test day records included for each cow. Estimates of .32, .19, and .20 for yields of milk, fat, and protein, respectively, were highest when only test d 3 to 7 were included; the corresponding estimates for 305-d records were .39, .32, and .30. Estimates of residual variances were reduced when test day records were converted to records of average yield in standardized intervals of 30 d. Breeding values were estimated for 305-d and test day models. A comparison of both sets of breeding values indicates only minor changes in sire rank, but more drastic reranking for individual cows. PMID- 7790585 TI - A model for reproductive efficiency of dairy bulls. AB - Reproductive efficiency of bulls is usually measured by nonreturn rate, which is commonly defined as the proportion of cows that were inseminated and did not return for another service within a specified number of days. The AI organizations use nonreturn rate to evaluate fertility of a bull or performance of a technician. Measures derived from nonreturn rate, such as conception rate and calving rate, might be more reliable for evaluation than nonreturn rate itself. Estimated conception rate is a better early measure of efficiency than nonreturn rate, because conception rate depends on the population of spermatozoa at insemination and not on developmental potential of the conceptus after insemination. A mathematical function is presented to model reproductive efficiency of bulls by estimation of the probability of conception at time of insemination (conception rate) and the probability of completing gestation after insemination (calving rate) through the relationship of nonreturn rate to the concentration of spermatozoa at insemination and the time after insemination. The model is illustrated with three bulls, using nonreturn rates by 28, 56, and 84 d after insemination. PMID- 7790588 TI - A diagnostic and prognostic tool for epidemiologic and economic analyses of dairy herd health management. AB - A computer program framework was established to enable a dairy herd production consultant to perform whole-herd analysis. The diagnostic process was an extensive data analysis 1) to derive key parameters related to production, reproduction, and health and 2) to produce input to a prognostic process. The prognostic process synthesized the obtained information into short- or long-term prognoses for the herd through a complex herd simulation model. Site specificity of parameter estimation and forecasting and explorability of assumptions and results were major characteristics of the approach. A user acceptance problem related to the simulation was addressed through a simultaneous process of development and validation during the introduction of the program framework into veterinary practices. The generally slow adoption of herd simulation models in extension work could be due to lack of credibility of the models. A major barrier to adoption of the current whole-herd approach may be the considerable time required to understand and use the tools properly. An example of a simulation experiment based on data from a New York dairy farm was provided, and the interpretation and practical applications of such simulations were discussed. PMID- 7790587 TI - Variance of interaction effects of sire and herd for yield traits of Holsteins in California, New York, and Pennsylvania with an animal model. AB - An animal model with a REML algorithm was used to estimate variances of additive genetic effects and interaction effects of sire and herd. Milk and fat yields were analyzed for first, second, and third lactations of Holsteins from California, New York, and Pennsylvania. Twenty samples of data were used in the study: 10 from California, 4 from New York, and 6 from Pennsylvania. Mean number of lactations per sample was 36,820 from 18,189 cows in 156 herds. Mean fractions of phenotypic variance of interaction effects of sire and herd for milk and fat yields were .015 and .019 for first lactation and .019 and .021 for all (up to three) lactations rather than the .14 used for national genetic evaluations in the US. Mean heritability estimates for milk and fat yields were .26 and .24 for first lactation and .21 and .21 for all lactations in California and .34 and .35 for first lactations and .28 and .29 for all lactations in New York. Sums of variances of permanent environmental and interaction effects of sire and herd were similar to those used for national genetic evaluations in the US. Analysis of another 10 samples from California and 10 samples from New York showed only slightly different fractions of phenotypic variance for milk yield for interaction effects of sire by herd, sire by herd by year, and sire by herd by year by season: .023, .027, and .037 for California and .023, .017, and .023 for New York, respectively. PMID- 7790589 TI - Quantity and economic importance of nine selected by-products used in California dairy rations. AB - Food processing representatives, brokers, nutritionists, livestock producers, and trade associations were surveyed to quantify 9 by-products used for feeding livestock during 1992 in California. The commodities were almond hulls, dried beet pulp, wet brewers grains, wet citrus pulp, pressed citrus pulp, wet corn gluten feed, corn gluten meal, whole cottonseed, and rice bran. The 9 by-products contributed over 2.5 million tonnes and about 27% of the total feed concentrate moved within California during 1992. Market value of these 9 by-products was almost .25 billion dollars. Whole cottonseed accounted for about 31% of the total tonnage of these 9 by-products and provided about 66% of the total CP and 53% of the total NEL of these 9 by-products. The by-products were more valuable as energy sources than CP sources compared with NEL from corn and CP from soybean meal, respectively. Calculations of milk production, based on the CP content or NEL content of the by-products, showed that these 9 by-products could have contributed sufficient CP or NEL for over 31% of the milk produced in California during 1992. Ration formulations demonstrated that the economic value of by products changed with feedstuffs available and, in general, would be used in rations over a range of market prices. PMID- 7790590 TI - The mouth that roared: effective advocacy in the nineties and beyond. PMID- 7790592 TI - Oral Candida: clearance, colonization, or candidiasis? AB - Candida albicans is frequently isolated from the human mouth, yet few carriers develop clinical signs of candidiasis. Oral candidiasis presents clinically in many forms. This reflects the ability of the yeast to colonize different oral surfaces and the variety of factors which predispose the host to Candida colonization and subsequent infection. Colonization of the oral cavity appears to be facilitated by several specific adherence interactions between C. albicans and oral surfaces which enable the yeast to resist host clearance mechanisms. Thus, Candida has been shown to adhere to complement receptors, various extracellular matrix proteins, and specific sugar residues displayed on host or bacterial surfaces in the oral cavity. Oral candidiasis results from yeast overgrowth and penetration of the oral tissues when the host's physical and immunological defenses have been undermined. Tissue invasion may be assisted by secreted hydrolytic enzymes, hyphal formation, and contact sensing. While these and other phenotypic characteristics may endow certain Candida species or strains with a competitive advantage in the oral cavity, it is the host's immune competence that ultimately determines whether clearance, colonization, or candidiasis occurs. PMID- 7790591 TI - Charting our future. PMID- 7790594 TI - Variability in microleakage observed in a total-etch wet-bonding technique under different handling conditions. AB - Using a stereoscopic clearing protocol and scanning electron microscopy, we investigated the extent and nature of microleakage in a total-etch, current generation dentin adhesive by a wet-bonding technique under different handling conditions. The hypotheses were that inadequate light curing of the primer or incomplete drying of the primer solvent might adversely affect the sealing ability of an acetone-containing adhesive system. The study consisted of three experimental groups: (I) a control group with an adequate light source and with the primer solvent completely dried; (II) an "inadequate-light" group; and (III) an "incomplete evaporation of primer solvent" group. The extent of microleakage after silver staining and clearing of the specimens was scored based on a modified five-point scale. Nonparametric statistical analysis (Kruskal-Wallis ANOVA) followed by a multiple comparison test (Dunn test) indicated significant differences among the three groups (p < 0.05). SEM examination of the restorative interface revealed that microleakage appeared to be initiated from the bonding resin-hybrid layer interface in all three groups, representing the weak link in the adhesive system. In addition, microleakage was characterized by 5 zones, each delineating a stage in a continuous array of progressively deleterious microleakage patterns variously distributed among the three groups. It was suggested that, while the bonding resin-hybrid layer interface represented the intrinsic weakness in an already much improved dentin adhesive, extrinsic factors such as the adequacy of the curing light and, more importantly, complete removal of the primer solvents can and should be avoided to preserve the structural integrity of the marginal seal. PMID- 7790595 TI - Mineral distribution and dimensional changes in human dentin during demineralization. AB - Many bonding agents require the dentin surface to be acid-etched prior to being bonded. Understanding the stability and morphology of the etched dentin surface is important for improving bond strength and reliability in these systems. In this study, the atomic force microscope was used to quantify dimensional changes that occur to fully hydrated dentin during demineralization with a pH 4.0 lactic acid gel. A high-resolution microtomography instrument, the x-ray tomographic microscope, was also used to quantify the mineral density distribution in the dentin as a function of etching time. The intertubular dentin surface shrank by less than 0.5 microns during etching, while the peritubular dentin receded at an initially rapid linear rate. The dentin surface retained its initial morphology, although it was more porous with the removal of the peritubular dentin. Beneath the etched surface, there were three major zones characterized by mineral density differences. The first zone was a fully demineralized collagen layer, subjacent to which was a partially demineralized zone of roughly constant mineral density. Immediately following the partially mineralized layer was normal dentin. The presence of the partially mineralized layer could be explained in terms of different transport rates in the peritubular and intertubular dentin. PMID- 7790593 TI - Effects of unpolymerized resin components on the function of accessory cells derived from the rat incisor pulp. AB - Monomeric resin components from dental composites are toxic to fibroblasts in culture and thus may interfere with the local immune system of the pulp, reducing its effective defense potential, either by cytotoxicity or by a more specific immune mechanism. Therefore, the present study was undertaken to observe the cytotoxic effects elicited by certain unpolymerized components of resin composites upon the function of accessory pulp cells in mitogen-induced proliferation of T-lymphocytes. Accessory cells from the rat incisor pulp were released following enzymatic digestion with collagenase. The assay included incubation of these cells with purified T-lymphocytes from cervical lymph nodes for 72 h in the presence of different concentrations of the resin components. The proliferative T-lymphocyte response was monitored by 3H-thymidine incorporation. Initially, we conducted experiments on spleen cells to determine the proper concentration intervals for suitable testing of the resin components. To assess the individual susceptibility of accessory cells and T-lymphocytes, we pre treated each of these cells with some of the test materials prior to assay. At low concentrations, urethane dimethacrylate (UDMA), bisglycidyl methacrylate (bis GMA), triethylene glycol dimethacrylate (TEGDMA), and bis-phenol A (BPA) increased spleen cell proliferation to concanavalin A (con A). Purified T lymphocytes stimulated by pulpal cells did not show enhanced responses to UDMA, bis-GMA, glycidyl mehtacrylate (GMA), or N,N,-dihydroxyethyl-p-toluidine (DHEpT). At higher concentrations, all substances except camphoroquinone (CAMP) showed inhibitory effects in both test systems. The in vitro study shows that resin components can evoke either immunosuppression or immunostimulation on mitogen driven proliferation of purified T-lyumphocytes and spleen cells. PMID- 7790596 TI - Mercury release from dental amalgams: an in vitro study under controlled chewing and brushing in an artificial mouth. AB - The release of mercury vapor from class I amalgam restorations prepared in human molar teeth was studied during chewing simulations in an artificial mouth of a bi axial servo-hydraulic mechanical test system. So that the total mercury released from the restoration over a fixed time could be determined, a closed chamber surrounded the envelope of chewing motion. In addition, the influence of sampling frequency on mercury release was corrected by the use of different sampling frequencies over a fixed time interval of mercury release measurement and extrapolation to zero sampling time. Thus, a combination of a closed environment and an extrapolation method to determine the mercury release under continuous sampling was used to determine the mercury released under normal breathing conditions. The measured mercury release rate data were used to calculate the potential daily mercury dose in a patient due to a single amalgam restoration, following the method previously outlined by Berglund. The mercury release from both a conventional and a high-copper amalgam was evaluated at different age intervals after the restoration was placed in the teeth. The results show that while the age of the amalgam and the amalgam type influence the extent of mercury release during the initial non-steady-state conditions, the steady-state value of mercury daily dose due to a single amalgam filling is 0.03 micrograms/day, which is well below the calculated threshold-limiting value (TLV) of 82.29 micrograms/day considered dangerous for occupational exposure in the United States. PMID- 7790597 TI - Cavity preparation with the Nd:YLF picosecond laser. AB - Several laser systems for the removal of hard dental substances are currently under investigation. However, in most cases, such systems have been demonstrated to be inefficient or have led to undesirable thermal side-effects. This paper reports, for the first time, the removal of enamel and dentin by a picosecond laser system, a solid-state Nd:YLF laser. Very precise cavities can be obtained in the enamel and dentin of extracted human molars when laser pulses are distributed onto well-defined areas of the teeth. Scanning electron microscopy shows that the quality of the cavities is superior to that achieved by other laser systems. The cavity walls are very steep, and their surfaces are characterized by a sealed structure. In contrast to laser systems with longer duration pulses, picosecond laser pulses ablate with less thermal damage to the surrounding substance. The results of dye penetration tests and polarized microscopy show that even mechanical shock-wave effects are negligible. When the Nd:YLF laser is applied to carious enamel, the ablation rate is found to be about ten times higher than for sound molars, thus making the Nd:YLF laser a caries selective laser system. PMID- 7790598 TI - Computer-assisted reconstruction of enamel fissures and carious lesions of human premolars. AB - The origin of cariogenesis in occlusal fissures remains elusive because of limited information about both the fissure structure and the morphologic details of carious lesions occurring there. The present study was aimed at reconstructing the coronal structure of human premolars with the aid of computer-assisted image analysis and, on the basis of the reconstructed structures, investigating the configuration of fissures, their proximity to the enamel-dentin junction (EDJ), and the occurrence and extension of carious lesions around the fissure walls. The coronal portions of the teeth were embedded in polyester resin and then ground off stepwise by hand. Serial images of the enamel contour on successive ground planes were recorded by objective microscopy after it was distinctly demarcated with either 0.5 w/v% carbol fuchsin or 1 w/v% basic fuchsin. Usually, from 150 to 250 photoprints were collected from a single enamel crown to reproduce the details of the fissure structures. The enamel outline (the occlusal and lateral surfaces, fissure walls, and EDJ) and, if present, the outline of caries-attacked areas were traced accurately on those photoprints by means of a digitizing system. The enamel contour data in series were input into an image analyzing system (Nikon COSMOZONE, 2SA). Observation of the computer-drawn coronal enamel allowed us to view the morphologic features of the fissures (shape, divarication, and proximity to EDJ) and to scrutinize the pathway of enamel caries along fissure walls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790599 TI - Quantifying the strength of bacterial adhesive interactions with salivary glycoproteins. AB - We adapted an assay that has been used to estimate the strength of eukaryotic cell-cell and cell-extracellular matrix adhesive interactions (McClay et al., 1981) to quantify the strength of bacterial (streptococci, fusobacteria, actinomyces) interactions with salivary receptors. Bacteria are centrifuged onto human submandibular/sublingual or parotid-saliva-coated microtiter wells. Plates are sealed with pressure-sensitive, double-sided tape which allows them to be inverted and centrifuged again. The force required to remove the bacteria from the coated wells is a direct measure of the adhesive strength of the interaction(s) being disrupted. The bacteria-saliva adhesive forces we detected ranged from 1.6 x 10(-8) dynes (Streptococcus sanguis 72-40) to > 1.1 x 10(-7) dynes (Actinomyces viscosus T14 V). These forces were in the range to withstand the shear stress produced by salivary flow, which we calculated as approximately 6.1 x 10(-7) dynes. PMID- 7790600 TI - Formation of differentiated tissues in vivo by periodontal cell populations cultured in vitro. AB - The periodontium contains heterogeneous mesenchymal cell populations with various differentiation potentials. The capacity of these cells for tissue formation as well as the origin of their precursors are still not entirely defined. In this study, cells originating from different periodontal tissues were cultured in vitro, and tissue formation in vivo following orthotopic re-implantation was investigated. Cells were recovered from the alveolar bone and periodontal ligament tissue of six minipigs, and cultured cells were then grown on extracted dental roots from the homologous animals by means of co-culture in vitro. Each minipig received 2 roots covered with alveolar bone cells, 2 roots covered with periodontal ligament cells, and 2 control roots (without cells) implanted into palatal bone defects. Intravital fluorochrome labeling was performed, and two minipigs were histologically examined after 2, 4, and 12 weeks in each case. Controls showed widespread resorption and ankylosis, whereas roots covered with cultured periodontal cells exhibited tissue formation in vivo. Alveolar bone cells synthesized a calcified cellular tissue resembling cellular cementum, suggesting that cells within this population might differentiate into cementoblasts when reimplanted with a dental substrate in vivo. Periodontal ligament cells exhibited no calcified tissue formation in vivo, but cells synthesized a connective tissue with orientated fiber bundles attached to both host bone and root, resembling periodontal ligament. PMID- 7790601 TI - Expression of basement membrane type IV collagen and type IV collagenases (MMP-2 and MMP-9) in human fetal teeth. AB - Formation and degradation of dental basement membrane (BM) are important for tooth development. Data on the expression of genes for type IV collagen (the major structural component of the BM) and type IV collagenases [MMP-2 (72 kDa) and MMP-9 (92 kDa)], enzymes that degrade type IV collagen during human tooth development, are lacking. We studied expression of type IV collagen and the MMP-2 and MMP-9 in human fetal teeth (from the 13th to the 20th gestational weeks, covering cap stage through early hard tissue formation). During cap and bell stages, in situ hybridization located transcripts for alpha 1 type IV collagen chain in the fibroblasts surrounding the enamel organ. No alpha 1 type IV collagen chain mRNA was detected in tooth germ epithelium or dental papilla. However, type IV collagen immunoreactivity was observed in BM underlying the dental epithelium up to the appositional stage. Transcripts for MMP-2 were located mostly in the cells of the dental papilla and follicle. Transient expression of MMP-2 mRNA was observed in the inner enamel epithelium of late cap/early bell-stage teeth. During early apposition, a high level of MMP-2 was confined to secretory odontoblasts. Transcripts for MMP-9 were detected by the sensitive reverse-transcription polymerase chain reaction (RT-PCR) in developing teeth. Thus, in dental BM, alpha 1 type IV collagen chain may be of mesenchymal cell origin. Further, MMP-2 but not MMP-9 may participate in remodeling and degradation of BM during human tooth morphogenesis. PMID- 7790602 TI - Effect of lung inflation on levator veli palatini muscle activity. AB - Palatal movements play a critical role in regulating oropharyngeal airflow during breathing. We hypothesized that these movements are coordinated with breathing movements via afferent signals from the lung. However, the control of palatal movements in relation to the lung remains unclear. This study was designed to define, by electromyographic techniques, the relationship between palatal movement and lung action during respiration. We performed tracheotomies on 12 mongrel dogs anesthetized with sodium pentobarbital and found that lung inflation augmented the activity of the levator veli palatini muscle (LVP). Two kinds of discharges were recognized during the expiratory pause following lung inflation. One was a continuous, low-amplitude discharge induced during apnea following lung inflation. The other was a transient, high-amplitude discharge which appeared immediately after lung inflation. Both of these response activities were eliminated by bilateral vagotomy. We thus concluded that palatal movements, which can regulate expiratory airflow resistance and cause switching from nasal to oral airflow, are under the control of vagal afferent signals from the lung. PMID- 7790603 TI - Is ARDS usually associated with right ventricular dysfunction or failure? PMID- 7790604 TI - Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome. AB - OBJECTIVE: To compare the effects of inhaled nitric oxide (NO) and an infusion of prostacyclin (PGI2) on right ventricular function in patients with severe acute respiratory distress syndrome (ARDS). DESIGN: Randomized prospective short-term study. SETTING: Post-surgical ICU in an university hospital. PATIENTS: 10 patients with severe ARDS referred to our hospital for intensive care. INTERVENTIONS: In random sequence the patients inhaled NO at a concentration of 18 parts per million (ppm) followed by 36 ppm, and received an intravenous infusion of PGI2 (4 ng.kg-1.min-1). MEASUREMENTS AND RESULTS: Inhalation of 18 ppm NO reduced the mean (+/- SE) pulmonary artery pressure (PAP) from 33 +/- 2 to 28 +/- 1 mmHg (p = 0.008), increased right ventricular ejection fraction (RVEF), as assessed by thermodilution technique, from 28 +/- 2 to 32 +/- 2% (p = 0.005), decreased right ventricular end-diastolic volume index from 114 +/- 6 to 103 +/- 8 ml.m-2 (p = 0.005) and right ventricular end-systolic volume index from 82 +/- 4 to 70 +/- 5 ml.m-2 (p = 0.009). Mean arterial pressure (MAP) and cardiac index (CI) did not change significantly. The effects of 36 ppm NO were not different from the effects of 18 ppm NO. Infusion of PGI2 reduced PAP from 34 +/- 2 to 30 +/- 2 mmHg (p = 0.02), increased RVEF from 29 +/- 2 to 32 +/- 2% (p = 0.02). Right ventricular end-diastolic and end-systolic volume indices did not change significantly. MAP decreased from 80 +/- 4 to 70 +/- 5 mmHg (p = 0.03), and CI increased from 4.0 +/- 0.5 to 4.5 +/- 0.5 l.min-1.m-2 (p = 0.02). CONCLUSIONS: Using a new approach to selective pulmonary vasodilation by inhalation of NO, we demonstrate in this group of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI. The increase in CI during PGI2 infusion is probably related to the systemic effect of this substance. PMID- 7790605 TI - Corticosteroid effect on early beta-adrenergic down-regulation during circulatory shock: hemodynamic study and beta-adrenergic receptor assay. AB - OBJECTIVES: The steroid effect on critically ill patients remains controversial. The aim of this study is to characterize the effect of methylprednisolone on the heart in a beta-adrenergically down-regulated condition. DESIGN: A prospective hemodynamic study and retrospective receptor assay. SETTING: Multidisciplinary ICU in a university hospital. SUBJECTS: 42 patients who required pulmonary arterial catheters and an additional 4 corpses who were available for study within 3 h of their deaths. INTERVENTION: Intravenous methylprednisolone (10 mg/kg). MEASUREMENTS AND RESULTS: We pursued a hemodynamic study following a glucocorticoid administration. In patients who had undergone a long term (> 72 h) catecholamine treatment, the cardiac index increased. In patients who had undergone a short term (1-72 h) catecholamine treatment and in patients with no record of catecholamine administration, the cardiac index showed no remarkable change. Among the corpses, who died soon after their arrival, and the patients, who later died in the ward and were available for further study, we measured beta adrenergic receptor density in the left ventricular myocardium. It was found that receptor density was decreased after long term catecholamine treatment. Methylprednisolone, on the other hand increased the receptor density. CONCLUSION: Methylprednisolone improved the cardiac index, intriguingly, in patients with long term catecholamine treatment in circulatory shock. Myocardial beta adrenergic receptor also increased in number after the administration of methylprednisolone. However, the hemodynamic improvement caused by methylprednisolone was not observed in patients without beta-adrenergic down regulation. PMID- 7790606 TI - Oxygen cost of breathing for assisted spontaneous breathing modes: investigation into three states of pulmonary function. AB - OBJECTIVE: We investigated the effects of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) on the oxygen cost of breathing (VO2resp) for different states of pulmonary function. Additionally VO2resp was measured during spontaneous breathing. DESIGN: This was done in a controlled and prospective study. Ventilatory modes were applied randomly. SETTING: Measurements were performed in a quiet room on volunteers (VOL) and inpatients treated for chronic obstructive pulmonary disease (COPD). Post-operative patients after aortocoronary bypass surgery (ACB) were studied on the cardio-thoracic intensive care unit just before and after extubation. PATIENTS: Healthy volunteers (n = 14), postoperative patients after aorto-coronary bypass surgery (n = 15) and patients with COPD (n = 9, xFEV1 47.7%) were the objects of study. INTERVENTIONS: Demand flow CPAP (5 mbar) and PSV (7 mbar, PEEP 5 mbar), using the Hamilton Veolar ventilator, were investigated in comparison to spontaneous breathing. MEASUREMENTS AND RESULTS: VO2 was measured by a Datex Deltatrac metabolic monitor. VO2resp was calculated by subtraction of total oxygen uptake (VO2tot) in controlled mode ventilation (CMV) from that in the respective spontaneous breathing mode. For VOL and COPD patients who were not intubated, a CPAP facemask connected to a short 7.5 mm tube was used as connection to the ventilator. Breathing spontaneously under a canopy system VOL showed a VO2resp of 4.5 +/- 4.0% compared to 9.2 +/- 3.5% for ACB and 15.4 +/- 7.7% for COPD. CPAP changed the VO2resp to 7.8 +/- 3.9%, 12.0 +/- 4.0% and 9.1 +/- 3.6% respectively. PSV reduced the VO2resp to 7.9 +/- 3.8% in ACB and 7.7 +/- 5.5% in COPD. CONCLUSIONS: This investigation confirms findings that postoperative patients have a mild increase in VO2resp. COPD exhibit the highest increase in VO2resp. Tracheal tubes, masks and CPAP on a demand flow apparatus increases VO2resp in volunteers and postoperative patients after cardiac surgery. The same amount of CPAP in contrary reduces VO2resp in patients with COPD. Pressure support ventilation can offset the additional VO2resp induced by CPAP but at the same level does not further reduce VO2resp in COPD patients. PMID- 7790607 TI - Alterations in circulating vasoactive substances in the critically ill--a comparison between survivors and non-survivors. AB - OBJECTIVE: Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients. DESIGN: Prospective study. SETTING: Clinical investigation on a surgical intensive care unit of an university hospital. PATIENTS: 60 consecutive patients suffering from trauma (n = 21) or postoperative complications (n = 39) were studied prospectively. The patients were divided into survivors (n = 27) and non-survivors (n = 33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND RESULTS: Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1 +/ 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3 +/- 7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO2/FIO2 decreased only in the non-survivors, whereas VO2 increased in the survivors (from 246 +/- 48 to 331 +/- 43 ml/min). Plasma levels of renin (from 206 +/- 40 to 595 +/- 81 pg/ml) and vasopressin (from 5.78 +/- 0.82 to 7.97 +/- 0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188 +/- 63 to 339 +/- 55 pg/ml) (p < 0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non survivors (from 3.62 +/- 0.68 to 9.37 +/- 0.94 pg/ml) during the study period (p < 0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics. CONCLUSIONS: Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors. PMID- 7790608 TI - Septic shock due to Pseudomonas aeruginosa in a previously healthy woman. AB - Pseudomonas aeruginosa septicemia rarely occurs in non-immunocompromised adults. We present a case of septic shock following Pseudomonas aeruginosa pneumonia in a previously healthy 48-year-old woman. The onset was sudden, with back pain, pyrexia and shock. Chest radiographs revealed pneumonia, and Pseudomonas aeruginosa was identified from blood and sputum cultures. Therapy with dopamine, piperacillin and fluid replacement led to a prompt recovery. Laboratory tests failed to reveal any immunological deficits. Including this case, only five cases of Pseudomonas aeruginosa septicemia in patients though to be non immunocompromised have been reported. Two remarkable features of this type of Pseudomonas infection are apparent: i) it commonly develops from pneumonia and ii) it has a better prognosis than that in immunocompromised hosts. PMID- 7790610 TI - Enterococcus faecalis colonisation and endocarditis in five intensive care patients as late sequelae of selective decontamination. AB - OBJECTIVE: To describe Enterococcus faecalis colonisation and endocarditis in 5 intensive care patients after treatment with selective decontamination (SDD). SETTING: Intensive care unit (ICU) in a general hospital. PATIENTS: The patients were admitted to the ICU because of adult respiratory distress syndrome, polytrauma (2 patients), abdominal aortic surgery and gastrointestinal surgery. Because these patients needed mechanical ventilation they received systemic cefotaxime and SDD (polymyxin E, amphotericin B and norfloxacin). RESULTS: Colonisation with E. faecalis was documented in all patients. Intravascular catheter-related infection with E. faecalis occurred in 4 patients. None of the patients received antibiotics active against, E. faecalis, because body temperature normalised after catheter removal. In the course of his ICU stay one patient died. Autopsy showed E. faecalis endocarditis. The other 4 patients recovered from their primary illness, but had to be readmitted after several months because of E. faecalis endocarditis. One of these patients died. One patient recovered of endocarditis, but one year later valve surgery was necessary. The other 2 patients needed acute valve replacement. The latter 3 patients survived. CONCLUSION: We observed 5 patients with E. faecalis endocarditis as a late and severe sequela of SDD during their ICU stay. PMID- 7790611 TI - Excessive hypokalemia and hyperkalemia following head injury. AB - A sudden decrease of serum potassium below 2.5 mmol/l carries the risk of dangerous arrhythmias and requires immediate replacement therapy [6]. We refer to a patient with a brain stem compression after head injury, who developed a profound hypokalemia (K+ = 1.2 mmol/l) with life-threatening arrhythmias, probably due to a catecholamine induced intracellular potassium shift (beta-2 stimulation). Only by aggressive potassium replacement up to 80 mmol/h (610 mmol/16 h) could potassium levels be increased and cardiac arrhythmias terminated. Although replacement therapy was stopped when the serum K(+)-level increased to 2.4 mmol/l, 3.5 h later the patient became hyperkalemic (8.1 mmol/l). This was probably due to a secondary shift of potassium from intra- to extracellular space. In patients with severe head trauma and the potential risk of excessive catecholamine release special attention must be paid to changes in potassium balance. PMID- 7790609 TI - Toxoplasma pericarditis in acquired immunodeficiency syndrome. AB - Large pericardial effusions are now a well-known complication of the acquired immunodeficiency syndrome, mainly caused by mycobacterial disease. However, other etiologies can be found. We report a case of toxoplasma pericarditis without other parasitic localizations. Pericarditis is a very uncommon clinical feature during toxoplasmosis. Its diagnosis is often difficult to establish, particularly in immunocompromised patients. Nevertheless, its possible evolution to constriction or tamponade requires its consideration. New methods of rapid tissue cultures may be helpful and allow early specific treatment. PMID- 7790612 TI - Massive vasopressin-resistant polyuria induced by dexamethasone. AB - A case of severe polyuria elicited by intravenous administration of a normal pharmacological dose of dexamethasone is reported. The polyuria did not respond to treatment with vasopressin. A 15-year-old girl with a brain tumour was referred for surgery. After induction of anaesthesia she received dexamethasone 4 mg i.v., and developed a massive polyuria with hourly diuresis of up to 1250 ml. There was no response to treatment with vasopressin in doses well above those normally used. The patient did not fulfil any known cause of diabetes insipidus, and to our best knowledge, this case is the first with glucocorticoid-induced and vasopressin-resistant polyuria ever reported in man. PMID- 7790613 TI - Retinopathy of prematurity. AB - This review deals with retinopathy of prematurity (ROP), a disease characterized by retinovitreal neovascularization, eventually retinal detachment and blindness. Due to the increasing number of extremely premature newborns, it is becoming more frequent. ROP of all stages occurs in 25-35% of surviving premature newborns of gestational age up to approximately 35 weeks. Stages 3 or more occur in 5-10%, blindness in 3-5% of very immature babies. The incidence is inversely related to gestational age. Classification is internationally unified (ICROP) and describes 5 stages. Its pathogenesis has not yet been clarified. More or less proven risk factors are retinovascular immaturity, hyperoxia and possibly circulatory and respiratory instability. Prophylaxis consists in avoiding hyperoxia, and probably also in keeping the extremely premature newborn stable. Ophthalmologic examinations must be performed by ophthalmologists experienced in this field or under their direct responsibility and must be standardized. Treatment of ROP can be carried out at a certain stage by coagulation therapy. PMID- 7790614 TI - Apnea testing in suspected brain dead children--physiological and mathematical modelling. AB - OBJECTIVE: To study the validity and safety of the traditional apnea test in children, and to evaluate a mathematical equation estimating the hemodynamic response to the apnea test. DESIGN: A prospective clinical study. SETTING: Pediatric ICU. PATIENTS AND PARTICIPANTS: 38 pediatric patients suffering severe brain injury aged 2 months to 17 years, undergoing apnea testing for brain death. MEASUREMENTS AND RESULTS: Apnea tests were performed 61 times (once in 19 patients, twice in 15, and 3 times in 4 patients). Mean PaCO2 was 41.1 +/- 10.6 mmHg before apnea and increased to 68.0 +/- 17.6 at 5 min. PaCO2 increased to 81.8 +/- 20.1 and 86.0 +/- 25.6 at 10 and 15 min, respectively. There was a mean PaCO2 increase by 5.38 +/- 1.4 mmHg/min in the first 5 min, and 2.75 +/- 0.5 mmHg/min during the next 5 min. We found a statistically significant (p < 0.05) linear relationship between the natural logarithm of PaCO2, time, and the logarithm of the initial level of PaCO2. An inverse linear relationship (p < 0.05) was found between systemic mean arterial pressure (MAP) and initial level of PaCO2 presented as mathematical correlations and nomograms. CONCLUSIONS: By using our model for predicting MAP and PCO2 prior to apnea testing, hemodynamic embarrassment can be anticipated and prevented, thus allowing a safer procedure in the detection of brain death. Despite the fact that continuous cardiorespiratory monitoring is important, hemodynamic disturbances can be estimated before the apnea test, thus allowing a safer approach to brain death detection. PMID- 7790615 TI - Flumazenil in the treatment of hepatic encephalopathy in children with fulminant liver failure. AB - OBJECTIVE: To evaluate the effect of flumazenil on hepatic encephalopathy complicating fulminant liver failure in children. DESIGN: Uncontrolled prospective study. SETTING: Pediatric Intensive Care Unit, tertiary care center. PATIENTS: 9 children with fulminant liver failure and hepatic encephalopathy awaiting emergency liver transplantation. INTERVENTIONS: Changes in hepatic encephalopathy grade and in electroencephalogram were recorded during the injection of a bolus of flumazenil (0.01 mg/kg/i.v. bolus) followed by a continuous infusion of flumazenil (0.01 mg/kg/h). MEASUREMENTS AND MAIN RESULTS: Before flumazenil, 7 children had grade 2 and 2 had grade 3 hepatic encephalopathy. Flumazenile injection mediated an arousal effect in 1 child in whom encephalopathy improved from grade 3 to grade 2. This effect lasted 30 min. No clinical response was observed in other children. An improvement of EEG anomalies was observed lasting 3 min in one child. Despite continuous infusion of flumazenil, encephalopathy worsened in all children. CONCLUSION: The effect of intravenous administration of flumazenil on hepatic encephalopathy in children with fulminant liver failure is inconsistent. Its efficacy is transient. The therapeutic value of flumazenil in children with fulminant liver failure awaiting a liver graft is minimal at this dosage. PMID- 7790616 TI - Reliability of clinical assessments of respiratory system compliance (Crs) made by junior doctors. AB - OBJECTIVE: To assess the reliability of estimates of static respiratory system compliance (Crs) made by junior hospital doctors caring for ventilated newborn infants. DESIGN: A prospective comparison of junior doctors' estimates of Crs to the Crs measured immediately afterwards. SETTING: A regional neonatal intensive care nursery in Edinburgh, Scotland. PATIENTS: 46 ventilated newborn infants. MEASUREMENTS AND RESULTS: Crs was estimated by three grades of junior doctor (Senior House Officer, Registrar and Research Fellow) using two different methods, (i) based on visual assessment of tidal volume in relation to inflation pressure (optical Crs) and (ii) directly using a visual analogue scale (analogue Crs). The Crs was then measured immediately afterwards using the single breath passive expiratory flow technique. The differences between the estimates and the measurements were calculated for each grade of observer and plotted against the corresponding measurements. The relationship between estimates and measurements was also expressed in terms of the coefficients of determination r2 calculated by least squares regression. With both methods of estimation observers tended to overestimate the Crs of infants with lower measured Crs and underestimate that of infants with higher measured Crs with many estimates differing from the measurements by more than 50%. Values of r2 ranged from 0.086 to 0.481 indicating a weak relationship between the estimates and the measurements. CONCLUSIONS: Junior doctors' estimates of Crs were unreliable and did not represent a useful method of assessing respiratory function. The clinical use of compliance measurements merits wider evaluation. PMID- 7790617 TI - Surfactant adjunctive therapy for Pneumocystis carinii pneumonitis in an infant with acute lymphoblastic leukaemia. PMID- 7790619 TI - In vivo proton magnetic resonance spectroscopy in a case of Reye's syndrome. AB - A case of a 14-year-old boy with Reye's syndrome (RS) and complete neurologic recovery is presented. 1H magnetic resonance spectroscopy was performed on days 1 (admission to ICU), 8 and 62: During the acute phase of RS substantial cerebral metabolic imbalances were observed and their normalization monitored. The spectra from day 1 featured extremely high glutamine content (approximately 18 mmol/kg excess) and low concentrations of choline compounds pounds (approximately 1 mmol/kg deficit). Also some excess lactate was present. The subsequent spectra demonstrated the return to an almost normal brain metabolite profile. PMID- 7790620 TI - The fluidised bed. AB - The process of fluidisation involves blowing warm air through small solid microspheres thus creating a liquid, without wetness. The warmth provides some important properties including reducing the metabolic rate in thermal injury which has a beneficial effect on mortality, modifying catabolism after surgery, providing gradual vasodilation in shock and core temperature stability in illness. The fluidisation ensures prevention and successful treatment of pressure sores, a comfortable and less stressful environment than conventional care, a reduction in pain, ease of wound care, discourages a bacterial persistence and reduces the work of the nurse. The importance of proper fluid balance, bacteriological care and limitations of posture must be appreciated in using the bed. PMID- 7790618 TI - Severity scores in meningococcal septicemia and severe infectious purpura with shock. PMID- 7790622 TI - Treatment of a bronchial rupture by bronchoscopic fibrin sealant application. PMID- 7790623 TI - Acute stress bleeding prophylaxis with sucralfate versus ranitidine and incidence of secondary pneumonia in intensive care unit patients. PMID- 7790621 TI - Neutrophil-mediated tissue injury and its modulation. AB - Neutrophils play a key role in the development of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Since the lungs are the main target in these syndromes, with adult respiratory distress syndrome (ARDS) as the outcome, extensive research has been undertaken to prevent or mitigate ARDS. As evidence of the involvement of neutrophils in ARDS has accumulated, modulation of their function has become a major goal in terms of a therapeutic approach. In this short review, we sought to update our knowledge about neutrophils. Firstly, we summarized the various stimuli which activate neutrophils. Secondly, we described the different mediators, including cytokines, which are released by neutrophils. Lastly, we discussed the possible modulation of their function. Although we cannot assess the clinical usefulness of biochemical substances merely on the basis of their in vitro effects, understanding these mechanisms is fundamental to the success of the new therapeutic approach which is currently under way. PMID- 7790624 TI - Pulmonary edema after hydrogen peroxide irrigation of a war wound. PMID- 7790626 TI - Evolution of sigmoid intramucosal pH during orthotopic liver transplantation. PMID- 7790625 TI - High-dose intravenous IgG treatment and acute renal failure. PMID- 7790627 TI - Task difficulty and cognitive deficits in schizophrenia. AB - Investigators of schizophrenic cognition often produce 2 or more tasks of differing difficulty levels by manipulating a variable that affects the accuracy of both normal and schizophrenic individuals; the investigators find that the variable also affects the difference between the groups in accuracy and conclude that the variable taps a schizophrenic differential deficit. An alternative hypothesis is that task differences in true-score variance artifactually produce the finding. For free-response tasks, group differences tend to be larger when difficulty is near 50%. The authors illustrate a new method of controlling this artifact by selecting items for hard and easy tasks on opposite sides of 50% difficulty and equidistant from it. Using this design with an anagram task, they found that schizophrenic and normal individuals differ no more on hard anagrams than on easy ones, and they propose the design for testing hypotheses concerning schizophrenic deficit on tasks that differ in difficulty. PMID- 7790629 TI - Verbal interactions in the families of schizophrenic and bipolar affective patients. AB - Do verbal interactions between psychiatric patients and family members covary with the diagnosis of the patient? This study compared relatives (usually parents) of schizophrenic (n = 42) and bipolar (n = 22) patients on affective style (AS) or emotional-verbal behavior toward patients in family interaction. Patients were compared on coping style or verbal interactional behavior toward relatives. Relatives of schizophrenic patients made more negative AS (particularly intrusive) statements to patients than relatives of bipolar patients. Schizophrenic patients made fewer supportive statements and more self denigrating statements to relatives than bipolar patients. Among families of bipolar patients, negative AS in relatives was associated with oppositional, "refusing" styles in patients. Implications for psychosocial interventions with these disorders are discussed. PMID- 7790628 TI - Expressed emotion and subclinical psychopathology observable within the transactions between schizophrenic patients and their family members. AB - The authors examined whether young, recently discharged schizophrenic patients from high (n = 34) and low (n = 14) expressed emotion (EE) families differ in their level of subclinical symptomatology during a direct interaction task. Compared with patients from low-EE homes, patients from high-EE home showed significantly more odd and disruptive behavior with family members. High-EE relatives were more likely than low-EE relatives to respond with criticism to the first unusual thought verbalized by the patient; when this occurred, the probability of a second unusual thought was augmented. Results suggest that high EE family members may display negative attitudes toward patients in part because they are exposed to higher levels of unusual or disruptive behavior than low-EE relatives. The data also support a bidirectional, transactional model of the relationship between relatives' EE and patients psychopathology. PMID- 7790630 TI - Bodily shame as a mediator between abusive experiences and depression. AB - The role of bodily shame as a mediator between sexual or physical abuse and depression was investigated in a community sample of 101 women who had been followed for 8 years. In general, childhood and adult abuse were related to the occurrence of depression in the study period but when both were considered together, only adult abuse showed an independent association. However, childhood and adult abuse were both independently related to chronic or recurrent depression. Bodily shame was related to childhood abuse, and this association could not be accounted for by bodily dissatisfaction or low self-esteem. Bodily shame, but not childhood abuse, was related to chronic or recurrent depression when both factors were considered together and current depressive symptoms were controlled. PMID- 7790631 TI - Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis. AB - Numerous studies suggest that the relatives of schizophrenic patients exhibit neuropsychological impairments that are milder yet similar to those seen among schizophrenic patients. The authors assessed 35 nonpsychotic relatives of schizophrenic patients and 72 normal controls using a clinical and experimental neuropsychological test battery. Three neuropsychological functions met criteria for risk indicators of the schizophrenia genotype: abstraction, verbal memory, and auditory attention. These findings could not be attributed to parental socioeconomic status, education, general visual-spatial ability, or psychopathology. Furthermore, exploratory analyses were performed to determine whether the diagnostic efficiency of the indicators could be adjusted to meet the needs of genetic linkage analyses. These analyses suggest that psychometric considerations may help to create measures for genetic linkage studies. PMID- 7790632 TI - Depressed and normal individuals differ both in selection and in perceived tonal quality of positive-negative messages. AB - Twenty college undergraduates (10 depressed, 10 nondepressed, in terms of the Beck Depression Inventory and the Structured Clinical Interview for the DSM-III R) chose freely from a positive or negative tape-recorded message. They also rated the tonal quality of each tape. The nondepressed group selected the positive message more often than the negative message. However, the depressed group showed no difference in tape preference. The nondepressed individuals rated the negative tape as inferior in tonal quality, whereas no difference in tonal quality was reported by the depressed individuals. Results appear to support a response set not only toward positive cognitions among nondepressed individuals, which is absent among depressed individuals, but also toward perceived tonal quality differences. PMID- 7790633 TI - Fear-relevant illusory correlations: what types of associations promote judgmental bias? AB - A. J. Tomarken, S. Mineka, and M. Cook (1989) found that high-fear individuals markedly overestimated the covariation between fear-relevant stimuli and aversive outcomes. The authors assessed what features of stimulus-outcome associations promote illusory correlations. In Experiment 1, participants with high snake fear exhibited significant covariation bias for slides of snakes and shocks, but not for slides of damaged electric outlets (DEOs) and shocks. In Experiment 2, individuals with high and low snake fear rated DEOs and shocks as belonging together better than snakes and shocks. However, the shapes of high-fear individuals' affective response profiles to snakes and shocks were more similar than their profile shapes involving other pairings. In addition, their affective responses to snakes and snake-shock profile similarity predicted snake-shock belongingness ratings. These results suggest the importance of emotional responses and emotional profile similarity in mediating illusory correlations involving fear-relevant stimuli. PMID- 7790634 TI - Patterns of perceptual asymmetry in depression and anxiety: implications for neuropsychological models of emotion and psychopathology. AB - More than 1,000 university undergraduates were simultaneously classified as either high or low depressed and high or low anxious and given a face-processing task that typically elicits a left hemispatial bias. Depression and anxiety were associated with opposing biases in perceptual asymmetry scores. In particular, high-depressed students had smaller left hemispatial biases than low-depressed students, whereas high-anxious students had larger left hemispatial biases than low-anxious students. The results suggest that depression and anxiety may be associated with different patterns of asymmetric hemispheric function. Because the rate of comorbidity of depression and anxiety in the population is high, these findings confirm the importance of separating anxiety and depression when examining the relationship among patterns of brain activity, emotion, and psychopathology. PMID- 7790635 TI - Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD. AB - The authors examined the siblings of 140 attention-deficit hyperactivity disorder (ADHD) and 120 control probands and classified families as antisocial if the proband had conduct disorder or a parent had antisocial personality. Partial support was found for the hypothesis that the ADHD gender effect would be limited to antisocial families. Boys had an increased risk for ADHD compared with girls, but only among siblings from antisocial families. The effect size for predicting ADHD in siblings of probands was greater for maternal compared with paternal ADHD, but only for families exhibiting antisocial disorders. Strong support was found for the hypothesis that, compared with siblings from nonantisocial families, those from antisocial families would have more psychopathology (ADHD, depression, substance use, and conduct disorders). The presence of antisocial disorders signals a distinct subtype of ADHD. PMID- 7790636 TI - Onset and staging of DSM-IV alcohol dependence using mean age and survival-hazard methods. AB - Orderly onset of psychiatric symptoms has implications for both case detection and the construct validity of the underlying illness. Mean age and survival hazard techniques were used to study the onset of alcohol abuse and dependence (as defined in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1994) in 369 clinical cases drawn from a heterogeneous regional sample. The methods provided a similar general pattern of symptom sequencing, though only survival-hazard analysis described a punctuated onset of alcoholism in 3 discrete stages: alcohol abuse, dependence, and accommodation to the illness. This model survived a rigorous program of tests for goodness of fit and described the majority of the sample, supporting the construct validity of both alcohol abuse as a discrete first illness phase and of dependence as a set of core constructs distinct from and succeeding abuse. The specific strengths of survival-hazard analysis as a research tool in illness staging research are discussed. PMID- 7790637 TI - Individual differences in spatial working memory in relation to schizotypy. AB - With a delayed-response task, spatial working memory function was assessed in normal students who were selected for schizotypy. The Wisconsin Card Sorting Test was also administered. Twenty-eight undergraduate students who scored high on the Perceptual Aberration Scale (PerAb) and 23 who scored low on this scale participated in this study. High PerAb students performed less accurately compared with the low PerAb controls on the delayed-response task, and they were more than twice as likely as low PerAb students to be impaired. The groups did not differ in the number of perseverative errors or number of categories achieved on the Wisconsin Card Sorting Test, but, as predicted, high PerAb students were less able to maintain set than were the low PerAb students. Neuropsychological implications of these data are discussed. PMID- 7790638 TI - The price of soliciting and receiving negative feedback: self-verification theory as a vulnerability to depression theory. AB - The hypothesis that people who seek and receive negative feedback are vulnerable to increases in depressed symptoms was tested among 100 undergraduates and their roommates. Students and roommates completed questionnaires on their views of each other and on their own levels of negative feedback seeking, depressed and anxious symptoms, negative and positive affect, and self-esteem. Three weeks later, students and roommates completed the same questionnaires. Results were, in general, consistent with prediction. Students who reported an interest in their roommates' negative feedback and who lived with a roommate who viewed them negatively were at heightened risk for increases in depressed symptoms. These results could not be explained in terms of the variables' relations to trait self esteem. The symptom specificity of the effect was moderately supported. Implications for work on interpersonal vulnerability to depression are discussed. PMID- 7790639 TI - Fantasy proneness, DSM-III-R axis I psychopathology, and dissociation. AB - Two thirds of the fantasy-prone college students (16 of total N = 24) who scored in the upper 4% of the population on the Inventory of Childhood Memories and Imaginings (ICMI; S.C. Wilson & T. X. Wilson, 1981) and who were administered a diagnostic interview met the criteria for either a past or present Axis I diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987), compared with 31% of medium fantasy-prone students (8 of total N = 26) who scored within 1/2 a standard deviation of the mean on the ICMI. Fantasizers also reported a higher frequency of past diagnosis of major depression (50%) than nonfantasizers (12%) and more dissociative experiences and symptoms, as indexed by a structured interview. Contrary to certain estimates of the frequency of dissociative disorders in the general population, none of the participants in the study received an actual dissociative disorder diagnosis. For certain individuals, fantasy proneness can be associated with significant psychopathology. PMID- 7790640 TI - Subsyndromal unipolar and bipolar disorders: comparisons on positive and negative affect. AB - The authors examined the mood patterns of young adults with cyclothymia, intermittent depression, or no affective disorder in a nonclinical population. In a conceptual replication and extension of R. A. Depue et al. (1981, Study 5), participants completed a trait measure of mood and then completed daily mood ratings for 28 days. Individuals in the intermittent depression and cyclothymia groups were characterized by high levels of negative affect on trait and daily ratings. Both groups were also characterized by high variability of negative affect across days. Individuals with cyclothymia reported higher levels of trait and daily positive affect than individuals with intermittent depression and also exhibited high between-day variability on positive affect. Similarities and differences with R. A. Depue et al. (1981) are described and the results are discussed in terms of the common and differentiating features of the subsyndromal affective disorders. PMID- 7790642 TI - Correlates of psychosis proneness in relatives of schizophrenic patients. AB - The Magical Ideation Scale (MIS), Perceptual Aberration Scale (PABS), Social Anhedonia Scale (SAS), and Physical Anhedonia Scale (PAS) were administered to 98 relatives of schizophrenic patients along with a measure of personality disorders (the Personality Diagnostic Questionnaire--Revised). Hierarchical regression analysis indicated that the schizotypal and borderline personality disorder (PD) scales explained significant variance in both the MIS and PABS; the avoidant PD scale also explained significant variance in the PABS. The schizoid, paranoid, and avoidant PD scales explained significant variance in the SAS. Sibling intraclass correlations indicated a significant heritability of 0.62 for the PABS. PMID- 7790641 TI - Modification of performance on the span of apprehension, a putative marker of vulnerability to schizophrenia. AB - The present study examined the effectiveness of 2 types of intervention (contingent monetary reinforcement and enhanced instruction) on span of apprehension performance. Forty chronic schizophrenia inpatients (26 men, 14 women) received a 3- and 12-letter array version of the span of apprehension task 4 times: baseline, intervention, immediate posttest, and 1-week follow-up. All patients were randomly assigned to 1 of 4 groups that differed according to method of intervention: repeat administration, monetary reinforcement only, instruction only, and monetary reinforcement plus instruction. The combination of monetary reinforcement plus instruction yielded significantly greater improvement in span accuracy than the other methods of intervention. These findings suggest that performance on this putative vulnerability indicator can be modified through certain interventions. PMID- 7790643 TI - On the relation between IQ, impulsivity, and delinquency: remarks on the Lynam, Moffitt, and Stouthamer-Loeber (1993) interpretation. AB - A recent report by D. Lynam, M. Moffitt, & M. Stouthamer-Loeber (1993) examined the inverse relation between IQ and delinquency and concluded that the observed relation represents "an influence of compromised intelligence on delinquent behavior" (p. 193). Specifically, the role of impulsivity in understanding this relation was discounted. The author considers the conceptual, operational, and analytical bases of the Lynam et al. report and argues that their neurologically based view of "executive dysfunction" as underlying delinquency is selectively portrayed. It is further contended that IQ scores, used as their index of brain behavior relations, are only remotely related to specifiable neurological functioning. The Lynam et al. conclusion that impulsivity cannot appreciably explain the relation between IQ and delinquency is shown to depend on the analytical approach used. Analyzed alternatively, impulsivity emerges as the more important predictor that can mediate the observed IQ and delinquency relation. Social policy implications of these differing interpretations are noted. PMID- 7790644 TI - Choice of frequency weighting for the evaluation of weapon noise. AB - This paper describes a laboratory study to choose an appropriate frequency weighting network for predicting the annoyance caused by the noise from small, medium, and large weapons. The results indicate that the annoyance of all three weapon types is the same if the blasts are heard at identical A-weighted SEL's. On the other hand, equal C-weighted SEL's result in large differences in annoyance between the weapon types. The implications of these results for outdoor noise criteria depend on the assumption concerning window condition. If one assumes that people hear the blasts predominantly through open windows, then A weighted criteria should be appropriate for all the weapon types without any correction (penalty or bonus) for weapon type. On the other hand, if the blasts are heard predominantly through closed windows a penalty of about 5 dB should be applied to the outdoor levels of the large weapons to account for the poorer low frequency attenuation of the windows. PMID- 7790645 TI - Mechanical modeling of palatal snoring. AB - The mechanism of human snoring caused by vibration of the soft palate and the characteristics of the noise are investigated. The soft palate becomes unstable and vibrates violently once the inspiratory flow exceeds a critical speed. The physiological phenomenon is modeled by studying flow over a flexible plate. In determining the stability of this flow, the trailing edge conditions are crucial. It is found that the noise generated in the simple experimental configuration has distinct characteristics found in human snores. For example, there is an antiphase relation between unsteady pressures from the oral and nasal channels and this provides a feature that distinguishes snoring by vibration of the soft palate from that caused by other parts of the human airway. PMID- 7790646 TI - Subjective evaluation of four low-complexity audio coding schemes. AB - In this study the subjective performance of four low-complexity audio data compression methods are compared, operating at nominal bit rates of 2, 3, 4, and 5 bits per sample, applied to four 20-kHz bandwidth, 16-bits per sample digitized musical signals. The simple compression schemes compared were elementary differential pulse-code modulation (DPCM), noise feedback coding DPCM (NFC-DPCM), adaptive quantizer DPCM (DPCM-AQB), and a recently proposed method known as recursively indexed quantizer DPCM (RIQ-DPCM). Pairs consisting of a reconstructed signal and a reference signal were presented in a two-interval preference experiment. The reference signals were processed for specified levels of modulated noise reference unit (MNRU) in order to estimate the equality threshold rating (ETR) of the reconstructed audio stimuli. The subjective MNRU values were found to increase by 2-5 dB for each increment in bits per sample. The DPCM-AQB scores were found to be 8-10 dB higher than for DPCM and NFC-DPCM. RIQ-DPCM was rated highest, exceeding the DPCM-AQB results by 2-5 dB in all tests. Objective measurements of segmental signal-to-noise ratio (SNRSEG) for the reconstructed signals predicted a performance level 2-5 dB lower than was actually found in the subjective results, particularly for SNRSEG values below 25 dB. PMID- 7790647 TI - Processing of prosthetic heart valve sounds for single leg separation classification. AB - People with serious heart conditions have had their expected life span extended considerably with the development of the prosthetic heart valve especially with the great strides made in valve design. Even though the designs are extremely reliable, the valves are mechanical and operating continuously over a long period; therefore structural failures can occur due to fatigue. In this paper acoustical signal processing techniques developed to process noisy heart valve sounds measured by a sensitive, surface contact microphone are discussed. Measuring heart sounds noninvasively in a noisy environment puts more demands on the signal processing to extract the desired signals from the noise. Heart valve sounds are short-duration (10-20 ms) transients and therefore nonstationary, requiring more sophisticated processing algorithms to achieve the desired signal to-noise ratios. In this paper the preclassification signal processing is concentrated on exclusively. That is, the signal processing operations performed on the heart valve sounds prior to classification are discussed--a subject that will be developed in a future paper. Efforts are concentrated on the sounds corresponding to the heart valve opening cycle. Valve opening and closing acoustics present additional information about the outlet strut condition--the structural component implicated in valve failure. The importance of the opening sound for single leg separation detection/classification is based on the fact that as the valve opens, the disk passively hits the outlet strut. The opening sounds thus yield direct information about outlet strut condition with minimal amount of disturbance caused by the energy radiated from the disk. Hence the opening sound is a very desirable acoustic signal to extract. Unfortunately, the opening sounds have much lower signal levels relative to the closing sounds and therefore noise plays a more significant role than during the closing event. Because of this it is necessary to screen the sounds for outliers in order to insure a high sensitivity of classification. Because of the sharp resonances appearing in the corresponding spectrum, a parametric processing approach is developed based on an autoregressive model which was selected to characterize the sounds emitted by the Bjork-Shiley convexo-concave (BSCC) valve during opening cycle. First the basic signals and the extraction process used to create an ensemble of heart valve sounds are briefly discussed. Next, a beat monitor capable of rejecting beats that fail to meet an acceptance criteria based on their spectral content is developed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7790648 TI - Classification of prosthetic heart valve sounds: a parametric approach. AB - People with heart problems have had their lives extended considerably with the development of the prosthetic heart valve. Great strides have been made in the development of the valves through the use of improved materials as well as efficient mechanical designs. However, since the valves operate continuously over a long period, structural failures can occur--even though they are relatively uncommon. Here the development of techniques to classify the valve either as having intact struts or as having a separated strut, commonly called single leg separation, is discussed. In this paper the signal processing techniques employed to extract the required signals/parameters are briefly reviewed and then it is shown how they can be used to simulate a synthetic heart valve database for eventual Monte Carlo testing. Next, the optimal classifier is developed under assumed conditions and its performance is compared to that of an adaptive-type classifier implemented with a probabilistic neural network. Finally, the adaptive classifier is applied to a data set and its performance is analyzed. Based on synthetic data it is shown that excellent performance of the classifiers can be achieved implying a potentially robust solution to this classification problem. PMID- 7790649 TI - Relaxation dynamics of spontaneous otoacoustic emissions perturbed by external tones. I. Response to pulsed single-tone suppressors. AB - The dynamic aspects of the suppression of spontaneous otoacoustic emissions by external tones are evaluated. A Van der Pol oscillator driven by an external tone is used as an interpretive model for data on the pulsed suppression of spontaneous emissions obtained from six female subjects. Typical results for both the onset of, and recovery from suppression yield 1/r1 (where -r1 is the negative linear component of the damping function) in the range of 2-25 ms. In accordance with the predictions of the model, (a) the relaxation time for the onset of suppression increases with the amount of suppression induced by the external tone, (b) the values of r1 and the amplitudes of the unsuppressed emissions exhibit an inverse correlation, (c) the values inferred for r1 are not significantly dependent on the frequency of the pulsed suppressor tone, and (d) the inferred r1 values are not significantly dependent upon the amount of suppression. PMID- 7790650 TI - Relaxation dynamics of spontaneous otoacoustic emissions perturbed by external tones. II. Suppression of interacting emissions. AB - The level of a spontaneous otoacoustic emission (SOAE) during recovery from suppression by an external tone sometimes exhibits a prominent overshoot before reaching its normal level. At the onset of suppression, a less prominent undershoot is sometimes observed before the emission level stabilizes. The overshoot and undershoot are described in terms of the variable amount suppression produced by a neighboring higher-frequency SOAE which is responding more slowly to the modulation of the external tone. The variation of the SOAE amplitude during pulsed suppression is modeled by a pair of Van der Pol limit cycle oscillators with the primary oscillator linearly coupled to the displacement of the secondary high-frequency one. We have found relaxation time constants for the onset of suppression of the order of 4.5 and 7.4 ms for the primary and secondary SOAEs, respectively, and for the recovery from suppression 4.8 and 10.48 ms for the primary and secondary SOAEs, respectively. The same model is also successful in describing the release from suppression of the primary SOAE by the secondary SOAE when the latter is partially suppressed by the external tone. Aspirin administration reduces the magnitude of the overshoot by reducing the level of the higher-frequency SOAE and thereby eliminating the suppression of the lower-frequency one. PMID- 7790651 TI - Distortion product otoacoustic emission delay measurement in human ears. AB - The measurement of distortion product otoacoustic emission (DPOAE) delay using the phase gradient method is discussed. A short f2 sweep paradigm is described. Its merits are discussed and comparisons made with other methods. Using sweeps of less than 4%, consistent and reliable measurements were obtained from 12 normal ears, except for a few isolated measurements. Investigation of these apparent anomalies indicated that the short f2 sweep method was sensitive to the localized effects of narrow distortion product intensity notches and spontaneous emissions. It is possible that middle ear pressure instability or some local change in the cochlea sometimes compounded the situation. The intersubject range (63% of the mean) of DPOAE delay values was greater than the range of values observed due to measurement variability (5.6% of the mean) or intrasubject variability (8.5% of the mean) demonstrating that the method can detect real differences between ears. However, comparison with previous work shows that caution is needed in interpreting these data, as all DPOAE phase methods provide only partial latency values. The physical interpretation depends on both the stimulus sweep used and the origin of DPOAES. Our data shows that f1 sweep derived latency is lower than f2 sweep data by more than 20%. Caution also needs to be exercised when comparing cochlear traveling wave delay, as inferred from electrophysiological data, with that obtained from DPOAE delay measurements. PMID- 7790653 TI - Maximum-likelihood procedures and the inattentive observer. AB - In most experimental situations, it is expected that observers will achieve perfect detection at extremely high signal levels. Technically, it is assumed that the asymptote of the psychometric function is unity. In many practical psychophysical tests, such as those involving children, patients, or nonhuman animals, the observers are occasionally inattentive. Using computer simulations, it was assumed that inattention can be modeled as a stationary stochastic process whose major effect is to produce a psychometric function having an asymptote less than unity. A maximum-likelihood procedure was used to estimate threshold, because it has been shown to provide reasonably stable threshold estimates using very few observations. Inattention increases the variability of the threshold estimate, as would be expected, because inattention reduces the slope of the psychometric function. The simulations also show that the maximum-likelihood procedure poorly estimates the amount of inattention, and can, thereby, produce a strong bias in the threshold estimates, overestimating or underestimating the true values under different circumstances. Inattention appears to affect the two alternative forced-choice procedure more strongly than the yes-no (go/nogo) procedure. PMID- 7790652 TI - Identification of concurrent harmonic and inharmonic vowels: a test of the theory of harmonic cancellation and enhancement. AB - The improvement of identification accuracy of concurrent vowels with differences in fundamental frequency (delta F0) is usually attributed to mechanisms that exploit harmonic structure. To decide whether identification is aided primarily by selecting the target vowel on the basis of its harmonic structure ("harmonic enhancement") or removing the interfering vowel on the basis of its harmonic structure ("harmonic cancellation"), pairs of synthetic vowels, each of which was either harmonic or inharmonic, were presented to listeners for identification. Responses for each vowel were scored according to the vowel's harmonicity and that of the vowel that accompanied it. For a given target, identification was better by about 3% for a harmonic ground unless the target was also harmonic with the same F0. This supports the cancellation hypothesis. Identification was worse for harmonic than for inharmonic targets by 3%-8%. This does not support the enhancement hypothesis. When both vowels were harmonic, identification was better by about 6% when the F0's differed by 1/2 semitone, consistent with previous experiments. Results are interpreted in terms of harmonic enhancement and harmonic cancellation, and alternative explanations such as waveform interaction are considered. PMID- 7790654 TI - Comodulation masking release (CMR): effects of gating as a function of number of flanking bands and masker bandwidth. AB - Normal-hearing subjects participated in two CMR experiments. For experiment 1, two, three, five or nine 20-Hz-wide comodulated flanking bands were presented continuously or gated simultaneously with a 2000-Hz signal. The signal had a duration of 400 ms. Larger CMRs were obtained as the number of flanking bands increased for both the continuous and gated conditions. For fewer number of bands, the average CMR for continuous noise was substantially larger than for gated noise. As the number of bands increased, CMR increased more for gated than for continuous noise, and the difference between CMRs for gated and continuous noise decreased. Experiment 2 involved detecting a 400-ms 1000-Hz pure-tone signal in a seven-band comodulated noise complex. The noise bands, presented continuously or gated with the signal, were either 10, 20, 40, or 80 Hz wide. Larger CMRs were observed for continuous maskers and for smaller masker bandwidths; however, the effect of gating did not change significantly across bandwidth. The results of the first experiment indicate that the effects of gating on CMR are minimized when the number of auditory channels providing information is large. The results of the second experiment indicate that this effect is not simply a function of the large CMR magnitude obtained with a large number of flanking bands. PMID- 7790655 TI - The discrimination of samples of noise in monotic, diotic, and dichotic conditions. AB - Listeners' ability to discriminate between independent tokens of 800-Hz-wide bands of noise (centered at 1200 Hz) was measured in monaural, diotic, and several dichotic conditions. In a two-cue, two-alternative, temporal forced choice task, listeners indicated whether the second or third interval contained a token of noise that was different from the sample of noise that was presented in each of the remaining three intervals. Samples of noise were selected on a trial by-trial basis from a set of 50 independent noises for each hourly session. Six durations of noise, ranging from 10 to 328 ms, were utilized, and all were presented at an overall level of 79 dB. The baseline condition for comparisons of performance was a monaural presentation of the noises. As expected, discriminability improved when the baseline condition was presented diotically. The next best performance was obtained when the baseline stimuli was presented to both ears with the proviso that the noises were interaurally uncorrelated. Other dichotic conditions, all of which also utilized interaurally uncorrelated noises, produced performance that was worse than that obtained in the monaural condition. Large degradations in performance were observed when the left ear received a different sample of noise in each of the four intervals of a trial while the right ear continued to receive the baseline stimuli. This finding indicates that listeners were effectively unable to ignore the waveforms presented to one ear while performing a task which could be solved with the information presented to the other ear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790656 TI - Discriminating coherence in spectro-temporal patterns. AB - This study examined the ability of trained listeners to discriminate coherent components in randomly varying spectral patterns. In each observation interval, the listener was presented with a sequence of bursts of multitone complexes having a fixed number of tones (m) in each burst. In the standard interval, the frequency of each tone in every burst was chosen randomly between 200 and 5000 Hz. In the signal interval, the frequencies of n tones were repeated throughout the burst sequence while the remaining m-n tones were chosen at random. The n tones were coherent in the sense that they were perceived as "sticking together" to form a pattern. The listener's task was to discriminate which burst sequence contained the n components. The results indicated that discrimination improved with increasing n/m, with increasing number of bursts per interval, and declined as the coherent components were increasingly perturbed in frequency. Further, for a fixed value of the ratio n/m discriminability was relatively independent of m. A model incorporating multichannel filtering and an optimum decision rule was reasonably successful in accounting for the experimental results. PMID- 7790657 TI - Effects of level and frequency on the detection of decrements and increments in sinusoids. AB - Thresholds for the detection of decrements in level of sinusoidal signals were measured as a function of decrement duration, level (25, 40, 55, and 70 dB SPL) and frequency (250, 1000, and 4000 Hz) in eleven normally hearing subjects. Thresholds for detecting a brief increment in level were also measured. The sinusoids were presented in a background noise intended to mask spectral splatter associated with the decrement or increment. Performance tended to worsen with decreasing frequency, for all decrement durations and for increment detection. Performance also worsened with decreasing level. The results were analyzed using a model consisting of a compressive nonlinearity, a sliding temporal integrator, and a decision device. The analysis indicated that the worsening in performance with decreasing frequency and decreasing level can be attributed partly to increases in the equivalent rectangular duration (ERD) of the temporal integrator, but mainly to changes in the efficiency of the detection process following the temporal integrator; at lower frequencies and levels a larger change is required at the output of the integrator for threshold to be reached. At each frequency, the ERD was relatively invariant with level for levels more than about 20 dB above the absolute threshold. PMID- 7790658 TI - A developmental study of the perception of onset spectra for stop consonants in different vowel environments. AB - The importance of different acoustic properties for the perception of place of articulation in prevocalic stop consonants was investigated from a developmental perspective. Eight adults and eight children in each of the age groups, 5, 6, 7, 9, and 11 years, listened to synthesized syllables comprised of all combinations of [b d g] and [i a]. The synthesis parameters were adapted from Blumstein and Stevens [J. Acoust. Soc. Am. 67, 648-662 (1980)], and included manipulations of the following stimulus variables: formant transitions (moving or straight), noise burst (present or absent), and voicing duration (10 or 46 ms). Identification performance was high for all age groups across most stimulus types. Formant transition motion generally was not necessary for accurate identification, and there was no difference between age groups in terms of the perceptual weight placed on this cue. Furthermore, the results did not support the salience of duration as a developmental cue to place of articulation. The presence of a burst improved identification for the velar and alveolar places of articulation for all age groups, but was particularly important for the 11-year-olds and adults. These findings indicate that children, by age 5, do not rely on dynamic formant motion any more than adults do, and that the ability to integrate acoustic cues across regions of spectral change shows developmental patterns. PMID- 7790659 TI - The identification of vowel-like harmonic complexes: effects of component phase, level, and fundamental frequency. AB - These experiments investigate how the identification of vowel-like harmonic complexes, similar to those used by Leek et al. [J. Acoust. Soc. Am. 81, 148-154 (1987)], is affected by spectral contrast, overall level, component phase, and fundamental frequency (F0). Four normally hearing subjects were required to identify which of six vowel-like harmonic complexes was presented on each trial. The test stimuli were complex tones containing the first 35 harmonics of a 100-Hz fundamental or the first 70 harmonics of a 50-Hz fundamental. All of the harmonics with frequencies below 3000 Hz were equal in amplitude except for three pairs of successive harmonics which were located at the first, second, and third formant frequency values, and incremented in level by 1, 2, 4, 8, and 16 dB relative to the other components. Three overall levels were used, 85, 65, and 45 dB SPL, and harmonics were added in either cosine or random phase. The results indicated that identification was better for cosine phase than for random phase, except for the 100-Hz fundamental at 45 dB SPL. The difference between the two phase conditions increased with increasing presentation level and with decreasing fundamental frequency. The results are explained in terms of the waveforms that would occur at the outputs of different auditory filters. It does not appear necessary to invoke nonlinear enhancement mechanisms to explain the results, although an influence of such mechanisms cannot be ruled out. PMID- 7790660 TI - Frequency glide discrimination in the F2 region by normal-hearing and hearing impaired listeners. AB - The dynamic formant transitions present within consonant-vowel and vowel consonant utterances may be poorly processed by hearing-impaired (HI) listeners and may, as a result, provide reduced segmental information to these listeners. Both the brief durations and rapid spectral change associated with these transitions have been proposed as contributing to these deficits in processing. To investigate HI listeners' processing of transitional stimuli, six HI and six normal-hearing (NH) listeners were asked to discriminate between frequency glides patterned after second formant transitions in English CV syllables. The influences of glide duration, rate, and frequency extent were examined for each group in quiet and in broadband noise. Reductions in glide duration and the presence of noise each led to significant increases in frequency difference limens for glide onset. The magnitudes of these effects were similar across groups, thereby failing to show increased susceptibility to noise or greater deficits in dealing with brief stimuli on the part of HI listeners. Contrary to the expectation that HI listeners would show greatest deficits (relative to the NH group) for the most rapidly changing glides, the only significant group differences were observed for gradual glides of limited frequency extent. This latter finding is discussed in terms of sensitivity to "cochlear dispersion" cues [Porter et al., J. Acoust. Soc. Am. 90, 1298-1308 (1991)]. It is hypothesized that HI listeners may not process these cues as effectively as NH listeners, perhaps as a result of impaired frequency selectivity. PMID- 7790661 TI - Robust estimation of speech in noisy backgrounds based on aspects of the auditory process. AB - A new approach to speech enhancement is proposed where constraints based on aspects of the auditory process augment an iterative enhancement framework. The basic enhancement framework is based on a previously developed dual-channel scenario using a two-step iterative Wiener filtering algorithm. Constraints across broad speech sections and over iterations are then experimentally developed on a novel auditory representation derived by transforming the speech magnitude spectrum. The spectral transformations are based on modeling aspects of the human auditory process which include critical band filtering, intensity-to loudness conversion, and lateral inhibition. The auditory transformations and perceptual based constraints are shown to result in a new set of auditory constrained and enhanced linear prediction (ACE-LP) parameters. The ACE-LP based speech spectrum is then incorporated into the iterative Wiener filtering framework. The improvements due to auditory constraints are demonstrated in several areas. The proposed auditory representation is shown to result in improved spectral characterization in background noise. The auditory constrained iterative enhancement (ACE-II) algorithm is shown to result in improved quality over all sections of enhanced speech. Adaptation of auditory based constraints to changing spectral characteristics over broad classes of speech is another novel aspect of the proposed algorithm. The consistency of speech quality improvement for the ACE-II algorithm is illustrated over time and across all phonemes classified over a large set of phonetically balanced sentences from the TIMIT database. This study demonstrates the application of auditory based perceptual properties of a human listener to speech enhancement in noise, resulting in improved and consistent speech quality over all regions of speech. PMID- 7790662 TI - Acoustics, perception, and production of legato articulation on a digital piano. AB - This study investigated the perception and production of legato ("connected") articulation in repeatedly ascending and descending tone sequences on a digital piano (Roland RD-250s). Initial measurements of the synthetic tones revealed substantial decay times following key release. High tones decayed faster than low tones, as they did prior to key release, and long tones decayed sooner than short tones because of their more extensive prerelease decay. Musically trained subjects (including pianists) were asked to adjust the key overlap times (KOTs) of successive piano tones so that they sounded optimally, minimally, or maximally legato. The results supported two predictions based on the acoustic measurements: KOTs for successive tones judged to be optimally or maximally legato were greater for high than for low tones, and greater for long than for short tones, so that auditory overlap presumably remained more nearly constant. For minimal legato adjustments the effect of tone duration was reversed, however. Adjusted KOTs were also longer for relatively consonant tones (three semitones separation) than for dissonant tones (one semitone separation). Subsequently, KOTs were measured in skilled pianists' legato productions of tone sequences similar to those in the perceptual experiment. KOTs clearly increased with tone duration, an effect that was probably motoric in origin. There was no effect of tone height, suggesting that the pianists did not immediately adjust to differences in acoustic overlap. KOTs were slightly shorter for dissonant than for consonant tones. They also varied with position in the ascending-descending tone sequences, indicating that the pianists exerted strategic control over KOT as a continuous expressive dimension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790663 TI - Sonoelasticity imaging: theory and experimental verification. AB - Sonoelasticity is a rapidly evolving medical imaging technique for visualizing hard tumors in tissues. In this novel diagnostic technique, a low-frequency vibration is externally applied to excite internal vibrations within the tissue under inspection. A small stiff inhomogeneity in a surrounding tissue appears as a disturbance in the normal vibration eigenmode pattern. By employing a properly designed Doppler detection algorithm, a real-time vibration image can be made. A theory for vibrations, or shear wave propagation in inhomogeneous tissue has been developed. A tumor is modeled as an elastic inhomogeneity inside a lossy homogeneous elastic medium. A vibration source is applied at a boundary. The solutions for the shear wave equation have been found both for the cases with tumor (inhomogeneous case) and without tumor (homogeneous case). The solutions take into account varying parameters such as tumor size, tumor stiffness, shape of vibration source, lossy factor of the material, and vibration frequency. The problem of the lowest detectable change in stiffness is addressed using the theory, answering one of the most critical questions in this diagnostic technique. Some experiments were conducted to check the validity of the theory, and the results showed a good correspondence to the theoretical predictions. These studies provide basic understanding of the phenomena observed in the growing field of clinical Sonoelasticity imaging for tumor detection. PMID- 7790664 TI - Upper lip, lower lip, and jaw peak velocity sequence during bilabial closures: no differences between stutterers and nonstutterers. PMID- 7790665 TI - A definite and a semidefinite questionnaire version of the Hamilton/melancholia (HDS/MES) scale. AB - A definite (anchored) and a semidefinite (semi-anchored) questionnaire version of the Hamilton Depression Rating Scale (HDS) and the Bech-Rafaelsen Melancholia Scale (MES) were compared with the HDS/MES by observer-rating and self-rating of 24 patients fulfilling the DSM-3R criteria for major depressive disorder. Both types of questionnaire showed substantial agreement with the observer scale from which they were derived. The sum scores were for the definite questionnaires and the corresponding observer scales closely similar whereas the sum scores of the semidefinite questionnaires were significantly higher than the sum scores of the corresponding observer scales. These results indicate that patients' 'halo' effect may be avoided by using definite scaling criteria for self-rating. Thus, of the two versions of questionnaires the definite versions are recommended. PMID- 7790667 TI - Late-life depressive disorder in the community, early onset and the decrease of vulnerability with increasing age. AB - This study examined reports of a history of psychiatric illness related to age and depression in 4051 community residents aged 65-84. Depression was twice as common among subjects with a history of psychiatric illness before age 65. 78% of depressed subjects reported no history. The rate of reported history was inversely proportionate to the subjects actual age. This did not appear to be due to recollection bias but it did match the proportions previously reported to result from excess mortality of individuals with a psychiatric history. A psychiatric history may be an important risk factor for late-life depression but in the aging process after age 65 it may become increasingly uncommon. PMID- 7790668 TI - The relationship between premorbid neuroticism, cognitive dysfunction and persistence of depression: a 1-year follow-up. AB - In a previous report of patients with unipolar major depressive disorder, we found that deficits in autobiographical memory predicted depression levels over a 7-month interval. This follow-up examined predictors of recovery as defined by a period of 8 weeks with no or minimal symptoms of depression and examined the extra predictor variable, neuroticism. In a sample of 21 patients, episode duration was significantly correlated with high levels of premorbid neuroticism, dysfunctional attitudes and overgeneral autobiographical memories produced in response to emotionally negative cue words. When severity of depression was partialled out, high N score was significantly but independently correlated with each of these cognitive variables. The implication of these attitudinal and information processing biases were explored. PMID- 7790666 TI - Efficacy of the 'clonidine REM suppression test (CREST)' to separate patients with major depression from controls; a comparison with three currently proposed biological markers of depression. AB - We have shown that clonidine, infused i.v. during the second non-REM period, was significantly less REM sleep suppressant in depressed patients than in control subjects. We have named this procedure the 'clonidine REM suppression test (CREST)'. In this report, we compare in the same sample (15 patients with primary major affective illness, 10 normal controls, 15 patients with minor depression and 15 patients with generalized anxiety) the efficacy of the CREST to separate the major depressed patients from the control subjects with the efficacy of three currently proposed biological markers of depression, i.e., the latency of REM sleep, the dexamethasone suppression test and the clonidine growth hormone stimulation test. We found that the CREST had the highest efficacy and suggest that further studies with independent and larger samples of patients and controls are needed to confirm those preliminary results and establish if the CREST could provide a new biological marker of major affective disorders. PMID- 7790669 TI - Low parental care as a risk factor to lifetime depression in a community sample. AB - A number of studies have reported links between experiencing low parental care and subsequent depressive experience. As the majority have involved patient samples, links may reflect anomalous parenting disposing to help-seeking behaviour (and patient status) rather than directly to depression. We, therefore, report a community study, so redressing any such artefact emerging from a patient sample and, additionally, quantify the relevance of low parental care to depression in comparison to several other risk factors (i.e., age, gender, educational level, socioeconomic status and marital status). Subjects were drawn from the ECA study and comprised those assessed at the 1-year follow-up interview undertaken at the New Haven site, with parental care being assessed by a key item from the Parental Bonding Instrument (PBI). Those reaching criteria for a lifetime episode of major depressive disorder were significantly more likely to report low care from both parents as well as to be female, divorced or separated, and younger. Low parental care (along with age and mental status but not female sex) appeared pathoplastic in being linked with an increased chance of psychopathology in general, rather than demonstrating specificity to major depressive disorder. PMID- 7790670 TI - Social class in unipolar and bipolar probands and relatives. AB - 130 patients fulfilling DSM-III-R criteria for bipolar disorder (n = 62), bipolar disorder not otherwise specified (n = 19) and major depression (n = 49) were included in a comparative study on the occupational levels of uni- and bipolar probands and relatives. The occupational levels did not significantly differ between uni- and bipolar probands. An overrepresentation was found in the higher occupational class in bipolar probands' brothers and children. A comparison between the whole groups including probands and all their relatives revealed a social advantage both for male and female members of bipolar families. These results are in agreement with those of previous studies demonstrating an association between bipolar disorder and social achievement in relatives. PMID- 7790671 TI - 35% CO2 challenge in panic and mood disorders. AB - 20 patients with Panic Disorder (PD), 19 patients with Mood Disorder (MD) and 20 healthy controls inhaled one vital capacity of 35% CO2-65% O2 gas mixture and of compressed air in a double-blind, random, cross-over design. Only PD patients showed a strong reaction to 35% CO2 while MD patients and controls did not react significantly. These results support the specificity of the 35% CO2 challenge in PD patients and suggest that PD and MD are separate disorders. PMID- 7790672 TI - Decreased temporal lobe phosphomonoesters in bipolar disorder. AB - In vivo [31P]magnetic resonance spectroscopic imaging ([31P]MRSI) was performed on 12 unmedicated, euthymic bipolar patients and 14 control subjects to determine if there were alterations in high-energy P metabolism in the temporal lobes of bipolar patients. Compared with the control group, the patients with bipolar disorder demonstrated significantly lower phosphomonoesters (PME) in both the left and right temporal lobes. No other group differences in P metabolites or lateralized asymmetries were noted. This preliminary study provides support for altered temporal lobe phospholipid metabolism in bipolar disorder. PMID- 7790673 TI - The likelihood of recurrence in bipolar affective disorder: the importance of episode recency. AB - These analyses used a high-intensity follow-up of of patients with bipolar affective disorder to describe the immediate and long-term risks for recurrence and the importance of sustained recovery to those risks. At the baseline evaluation, all patients were in episodes of Research Diagnostic Criteria major depressive disorder, mania or schizoaffective disorder (excluding the mainly schizophrenic subtype); those who were depressed at intake had a history of mania or schizoaffective mania. Raters re-evaluated these patients at 6-month intervals for 5 years and annually for the remainder of a 10-year follow-up. The following report describes relapse risks for the 186 patients observed to recover from their index episodes. Survival analyses quantified the likelihood of relapse over time, beginning after symptom-free periods of 4 months and 1, 2 and 3 years. Further survival analyses used treatment status as a censoring variable to estimate the eventual likelihood of recurrence among those who reported sustained compliance with lithium prophylaxis; the prophylaxis group remained under observation until they relapsed, were lost to follow-up or ceased taking lithium. Progressively longer symptom-free periods were clearly associated with lower relapse risks over the subsequent 4 years. Thereafter, however, this effect dissipitated. 7 years after recovery, the cumulative likelihood of recurrence was four in five for all bipolar patients and two in three for those whose index episode had been followed by at least 3 years without symptoms. Even with sustained lithium prophylaxis, the likelihood of at least one recurrence exceeded 70% within 5 years of recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790674 TI - Seasonal variation in mood disorder presentation: further evidence of this phenomenon in a South African sample. AB - An earlier preliminary study conducted at Baragwanath Hospital in Soweto, South Africa, showed a statistically significant seasonal pattern for mood disorder presentation. These findings provided the basis for further exploration of the phenomenon. The present study replicates the earlier one in an attempt to establish the pervasiveness of the noted impact of season on mood disorder presentation. PMID- 7790675 TI - Induction of depressed and elated mood by music influences the perception of facial emotional expressions in healthy subjects. AB - The judgement of healthy subject rating the emotional expressions of a set of schematic drawn faces is validated (study 1) to examine the relationship between mood (depressed/elated) and judgement of emotional expressions of these faces (study 2). Study 1: 30 healthy subjects judged 12 faces with respect to the emotions they express (fear, happiness, anger, sadness, disgust, surprise, rejection and invitation). It was found that a particular face could reflect various emotions. All eight emotions were reflected in the set of faces and the emotions were consensually judged. Moreover, gender differences in judgement could be established. Study 2: In a cross-over design, 24 healthy subjects judged the faces after listening to depressing or elating music. The faces were subdivided in six 'ambiguous' faces (i.e., expressing similar amounts of positive and negative emotions) and six 'clear' faces (i.e., faces showing a preponderance of positive or negative emotions). In addition, these two types of faces were distinguished with respect to the intensity of emotions they express. 11 subjects who showed substantial differences in experienced depression after listening to the music were selected for further analysis. It was found that, when feeling more depressed, the subjects perceived more rejection/sadness in ambiguous faces (displaying less intensive emotions) and less invitation/happiness in clear faces. In addition, subjects saw more fear in clear faces that express less intensive emotions. Hence, results show a depression-related negative bias in the perception of facial displays. PMID- 7790676 TI - Further characterization of the inhibition of platelet aggregation by a plasma factor(s) in unmedicated unipolar depressed patients. AB - To investigate further the inhibition of platelet aggregation by a plasma factor(s) in unipolar depression, a series of assays were performed in which the platelet-rich plasma of a male volunteer was preincubated with the plasma of either unmedicated unipolar depressed patients or age-matched controls. Platelet aggregation was initiated by the following aggregating agents; ADP (10 and 2.5 microM), ADP/5HT (0.5 microM ADP + 50 microM 5HT and 0.5 microM ADP + 25 microM 5HT) and adrenaline (10 and 1 microM) (that act on different platelet membrane receptors) and by the following agents; sodium fluoride (20 mM), calcium ionophore A23,187 (19 microM) and phorbol-12-myristate-13-acetate (3.24 microM) (that act at specific intracellular sites). The plasma of depressed patients significantly reduced the platelet aggregatory response for each of the aggregating agents at each of the concentrations tested. Therefore, it is concluded that the inhibition of platelet aggregation by a plasma factor(s) may be irreversible in nature and may have an intracellular site(s) of action, possibly at, or beyond, the site of activated protein kinase C. PMID- 7790677 TI - Urinary catecholamines and plasma hormones predict mood state in rapid cycling bipolar affective disorder. AB - Over the course of 1 year, a patient with a rapid cycling bipolar affective disorder was followed at weekly intervals to examine whether plasma hormones and urinary catecholamines could predict current or future mood. Higher cortisol levels were found to predict depressed mood 3 days after blood sampling, higher urinary dopamine predicted a manic mood 3 days after blood sampling, urinary norepinephrine was associated with severity of current mood and prolactin was lower with concurrent depressed mood. In multivariate analyses of mood against cortisol, prolactin and three urinary catecholamines, > 50% of the variance in mood state in 3 days was explained by combinations of these biologic measures, especially cortisol and urinary dopamine, while all five biologic variables contributed to explaining 50% of the variance in current mood state. Based on the interrelationships between urinary dopamine, norepinephrine and mood, we postulate the existence of an overcompensating mechanism which is reflected in opposing correlations between urinary dopamine and norepinephrine with mood, despite the two urinary catecholamines being positively correlated. PMID- 7790678 TI - Which depressed patients respond to ECT? The Nottingham results. AB - The Nottingham electroconvulsive therapy (ECT) trial was designed with a simulated treatment group to test prospectively the power of delusions or agitation to predict response. The response of patients without retardation and without delusions was examined retrospectively as well because of doubts over the usefulness of ECT for this subgroup. Deluded/nondeluded and agitated/nonagitated subtypes responded significantly to real treatment. Neither delusions nor agitation predicted greater treatment response. Patients without retardation, with or without delusions responded to real ECT, supporting the continuing prescription of ECT for these patients as well. PMID- 7790679 TI - Do differences in sleep architecture exist between depressives with comorbid simple phobia as compared with pure depressives? AB - Sleep records from 19 subjects with major depression and comorbid simple phobia were compared retrospectively with 25 patients with major depression alone and 25 normal controls. Groups were matched for age and gender; depressed subjects were matched for severity of depression. All subjects had been free of psychotropic medications at least 2 weeks when recorded. Sleep variables were analysed using one-way ANOVA. Both depressed groups had significantly longer sleep latency than normal controls. Depressed patients with and without simple phobia showed no differences in sleep architecture. PMID- 7790680 TI - Platelet peripheral-type benzodiazepine receptor in major depression. AB - The peripheral-type benzodiazepine receptor (PBR) plays a major role in steroidogenesis. This receptor is sensitive to endocrine changes and stress. Antidepressants have been demonstrated to modulate adrenal and hepatic PBR in rats. To evaluate the relationship between depression and PBR, we measured platelet PBR in untreated depressed patients (n = 14) in comparison to normal controls (n = 13). Platelet PBR density (Bmax) and the dissociation constant (kd) of the receptor did not differ in the patients when compared with normal controls. Furthermore, no correlation was found between Bmax values and the severity of the depression (as measured by the Hamilton Depression Rating Scale and Beck Depression Inventory) as well as with the severity of the anxiety (as measured by the Hamilton Anxiety Rating Scale). It seems that major depression, in contrast to stress and some anxiety disorders, is not associated with alteration of PBR. PMID- 7790682 TI - Vitamin C and disease prevention. PMID- 7790681 TI - Caries diagnosis and risk assessment. A review of preventive strategies and management. AB - The scientific basis for caries risk assessment, prevention and treatment on an individual patient basis requires further development, specification and continuing validation. Still, current technologies and techniques, taken together, can provide enhanced capabilities over those that have been employed traditionally. Undoubtedly, the clinical tools for carrying out these responsibilities will be refined and expanded in the future in response to the changing clinical profile of caries in the population. For example, bacteriologic testing methods have become easier and more reliable, and will become more widely used. Other effective methods to detect the early, pre-cavitation stage of caries also should become more available in the future. Practitioners will be continually challenged and responsible for evaluating the effectiveness and value of emerging technologies in their practices and in light of their patients' needs. But how can this be accomplished best? Effectiveness claims will be made for new drugs and devices that come onto the market. There are several sources of information to assist the practitioner in making such decisions. The American Dental Association acceptance programs (voluntary) and the U.S. Food and Drug Administration compliance programs (law) provide standards and guidance as to product safety and effectiveness. Without such determinations, the practitioner must judge independently product claims and clinical studies. Marketing materials by themselves (advertisements, videos, pamphlets) may not be sufficient evidence of effectiveness particularly when scientific references supporting claims either are not provided or are inadequate. Peer-reviewed scientific literature in publications of the major scientific and professional associations can be viewed as generally reliable. Changing the way dental caries is managed in clinical practice will require integrating new scientific information and technology into workable clinical procedures. Dental education and third-party reimbursement issues must be addressed also but are beyond the scope of this document. Given that disease patterns are always changing in the population, dentists need to modify practice decisions using risk assessment. Ultimately, the goal for dentistry is that adult patients also will enjoy the same low level of caries experience that many children enjoy today. PMID- 7790683 TI - Vitamin C supplements and disease--counterpoint. PMID- 7790684 TI - Drug-nutrient interactions in medical training. PMID- 7790685 TI - Vitamin C and the common cold: a retrospective analysis of Chalmers' review. AB - In 1975 Thomas Chalmers analyzed the possible effect of vitamin C on the common cold by calculating the average difference in the duration of cold episodes in vitamin C and control groups in seven placebo-controlled studies. He found that episodes were 0.11 +/- 0.24 (SE) days shorter in the vitamin C groups and concluded that there was no valid evidence to indicate that vitamin C is beneficial in the treatment of the common cold. Chalmers' review has been extensively cited in scientific articles and monographs. However, other reviewers have concluded that vitamin C significantly alleviates the symptoms of the common cold. A careful analysis of Chalmers' review reveals serious shortcomings. For example, Chalmers did not consider the amount of vitamin C used in the studies and included in his meta-analysis was a study in which only 0.025-0.05 g/day of vitamin C was administered to the test subjects. For some studies Chalmers used values that are inconsistent with the original published results. Using data from the same studies, we calculated that vitamin C (1-6 g/day) decreased the duration of the cold episodes by 0.93 +/- 0.22 (SE) days; the relative decrease in the episode duration was 21%. The current notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written two decades ago. PMID- 7790686 TI - The health effects of vitamin C supplementation: a review. AB - A comprehensive review of the literature indicates that populations with long term consumption of higher than RDA levels of vitamin C (> or = 60 mg/day) from foods and/or supplements have reduced risks of cancer at several sites, cardiovascular disease, and cataracts. The safety of higher than RDA intakes of vitamin C is confirmed in eight placebo-controlled, double-blind studies and six non-placebo clinical trials in which up to 10,000 mg of vitamin C was consumed daily for up to 3 years. There are no clinical data which suggest that vitamin C's enhancement of non-heme iron absorption in individuals with low iron status could be a critical factor in the possible increased risk of heterozygous hemochromatosis-related cardiovascular disease. In fact, the cumulative data do not confirm that iron status is related to risk of cardiovascular disease. Moreover, higher than RDA intakes of vitamin C have been associated with several indices of lowered cardiovascular disease risk including increases in HDL, and decreases in LDL oxidation, blood pressure and cardiovascular mortality. PMID- 7790687 TI - Family medicine residents' knowledge and attitudes about drug-nutrient interactions. AB - OBJECTIVE: The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requires that health professionals recognize the importance of drug nutrient interactions and educate patients to prevent adverse effects. Drug nutrient interactions are an important issue in medical practice, but it is not clear how or if physicians are trained in this issue. METHODS: This investigation was a needs assessment that examined attitudes and knowledge about drug-nutrient interactions that was examined in a national sample of 834 family medicine residents in 56 residency programs. RESULTS: Most reported they had little or no formal training in drug-nutrient interactions in medical school (83%) or residency (80%). However, 79% believed it was the physician's responsibility to inform patients about drug-nutrient interactions, although many thought pharmacists (75%) and dietitians (66%) share this responsibility. Overall, residents correctly answered 61% +/- 19 of fourteen drug-nutrient interaction knowledge items. There was a slight increase in drug-nutrient knowledge as year of residency increased. CONCLUSIONS: Physicians' knowledge of drug-nutrient interactions may be improved by including nutrition education in the topics taught by physicians, nutritionists, and pharmacists using several educational strategies. Nutrition educators in particular can play a role in curriculum development about drug-nutrient interactions by developing, refining, and evaluating materials and educational tools. Nutrition educators need to provide this information in academic settings for the training of all health professionals as well as in patient education settings such as hospitals and public health clinics. PMID- 7790688 TI - Dietary intakes by levels of glycemic control for black and white adults with non insulin dependent diabetes mellitus (NIDDM). AB - OBJECTIVES: The relationship between diet and glycemic control was examined among a racially mixed population of male and female adults with non-insulin dependent diabetes mellitus (NIDDM). METHODS: Data from 3-day dietary records and glycosylated hemoglobin (HbA1c) were analyzed for two-hundred eighty two patients of a Family Practice Ambulatory Care Unit and a community-based health center in Winston-Salem, North Carolina. Correlations were calculated for individual nutrients to determine their strength of association with glycemic control. Analyses by tertiles of HbA1c were also conducted for each race/gender group. Regression analysis was used to determine independent dietary predictors of HbA1c. RESULTS: For all subjects, energy, energy per kilogram of body weight, fat, carbohydrates saturated fat, and cholesterol were significantly correlated with HbA1c. Nutritional differences across tertile levels of HbA1c for all subjects were not significant. For black females, consumption of energy, protein and fat was significantly higher among upper tertile subjects compared to the lowest tertile; and intake of energy, protein, fat, and saturated fat was significantly correlated with HbA1c in this group. For black males, energy intake was highest among upper tertile subjects compared to those in the middle tertile, while energy per kilogram of body weight, and percent of calories from protein, were significantly correlated with HbA1c. For white males, energy intake expressed as a function of body weight was highest among subjects in the upper tertile and a significant positive correlation with HbA1c was observed. No relationship between nutritional intake and HbA1c was found among white females. Racial differences in nutrient intake were also compared for males and females in the upper tertile of HbA1c. Black females in the upper tertile consumed significantly more energy, protein, and significantly less dietary fiber per 1000 kilocalories. No significant differences were observed between black and white males in the upper tertile, although higher cholesterol consumption in black males compared to white males approached significance. Regression analysis revealed that total energy intake significantly predicted HbA1c for all subjects and all white subjects, while a similar observation was made for total fat intake among all black subjects and among black females. CONCLUSIONS: These findings confirm that diet, especially total energy, is an important contributor to glycemic control. Dietary fat is also associated with glycemic control among blacks, especially black females, who are especially prone to more dire health consequences of NIDDM. Strict monitoring of diet should lead to improved glycemic control and less mortality and morbidity in this population. PMID- 7790689 TI - Protein consumption and hepatic encephalopathy in alcoholic hepatitis. VA Cooperative Study Group #275. AB - OBJECTIVE: Patients with alcoholic hepatitis frequently have moderate or severe malnutrition. Dietary protein intake may be restricted in these patients because of concurrent hepatic encephalopathy. To further evaluate the relationship between dietary protein intake and hepatic encephalopathy in alcoholic hepatitis, we evaluated prospectively gathered data from a study of 136 placebo-treated patients with moderate or severe alcoholic hepatitis conducted at eight Department of Veterans Affairs Medical Centers. METHODS: Physical examination, laboratory tests, and grade of hepatic encephalopathy were recorded at entry and every seventh day for the first 28 days of study. Average daily protein intake was calculated from dietary evaluation obtained by a registered dietitian at entry and again three times a week. RESULTS: Sixty-three percent of patients had hepatic encephalopathy at entry. Hepatic encephalopathy decreased over time. Time dependent regression analysis found low protein intake, along with high blood urea nitrogen (BUN) and high serum creatinine, to be independently associated with worsening hepatic encephalopathy. Similar analysis found low BUN and less malnutrition at entry into the study to be independently associated with improved hepatic encephalopathy. Higher protein intake was associated with improved hepatic encephalopathy in univariate (p = 0.01), but not multivariate, analysis. CONCLUSION: In patients with alcoholic hepatitis who can be treated with standard anti-encephalopathy medications (e.g., lactulose and neomycin), low protein intake is associated with worsening hepatic encephalopathy while a higher protein intake correlates with improvement in hepatic encephalopathy. PMID- 7790690 TI - Indicators of poor dietary habits in a high risk population. AB - OBJECTIVE: This study was conducted to determine whether individuals attending an urban outpatient clinic met the National Health Promotion and Disease Prevention nutritional objectives and to assess factors associated with poor dietary habits. METHODS: Individuals who attended the general medicine outpatient clinic at the State University of New York Health Science Center in Syracuse were interviewed using an expanded version of the Health Habits and History Questionnaire. Usual dietary intake, medical history, occupation, stress, physical activity, tobacco use and other life-style factors were recorded. Of particular interest were the percentage of calories from fat in the diet and whether individuals consumed the daily requirements of the base-foods in the USDA Pyramid (grains, vegetables and fruits). Unconditional logistic regression was used to determine odds ratios (OR) and 95% confidence intervals for variables associated with high fat consumption and low consumption of vegetables, fruit and high-fiber grains. RESULTS: None of the patients met the minimal recommended daily servings for the three base-food categories combined (grains, vegetables and fruits) and 84% of subjects had fat intakes which constituted over 30% of daily energy intake. Individuals with less education, who were disabled or unemployed, and who participated in little physical activity were twice as likely to have poor dietary habits (i.e. low consumption of vegetables, fruit, and/or high-fiber grains) as other subjects (p < 0.05). Younger patients (20-49 years of age), especially those who were nonsmokers and who reported little physical activity were more likely to consume fat and less likely to consume fruit than older patients (> or = 50 years of age). Nonwhite subjects were less likely to consume high-fiber grains and whole wheat breads than white patients (p = 0.04). CONCLUSIONS: Nutritional screening should be considered for all patients attending similar inner-city general medicine clinics, regardless of the primary diagnosis in order to provide early dietary intervention. In particular, young adults, the unemployed, and the disabled should not be overlooked. PMID- 7790691 TI - Effect of maternal oxygen therapy on placental calcium transport in intrauterine growth retarded rats. AB - OBJECTIVE: We tested the hypothesis that continuous maternal oxygen (O2) therapy leads to an increase in fetal survival, improvement in fetal growth, and correction of decreased placental calcium (Ca) transport, in pregnant rats who underwent uterine artery ligation. STUDY DESIGN: We measured on Day 21 of pregnancy, the unidirectional maternofetal clearance of 45Ca (Kmf45Ca) and 51Cr EDTA (Kmf51Cr-EDTA) across in-situ perfused placentas of rats randomized on Day 17 to a modified Wigglesworth (bilateral uterine artery ligation) procedure (group WW, n = 8), to modified Wigglesworth and supplemental maternal O2 treatment (FiO2 0.40) (group WWO2, n = 8), or to a sham operation (group Sh, n = 8). Kmf51Cr-EDTA provides a measure of placental "porosity" or passive permeability. RESULTS: Maternal O2 therapy did not improve fetal survival, fetal growth, or placental Ca transport. CONCLUSION AND SPECULATION: Bilateral uterine ligation in the pregnant rat leads to IUGR and decreased placental Ca transport which cannot be corrected by maternal O2 therapy. PMID- 7790692 TI - Failure of vitamin E to protect cultured human arterial smooth muscle cells against oxysterol-induced cytotoxicity. AB - OBJECTIVE: The cytotoxicity of oxysterols including 7 alpha-hydroxycholesterol (7 alpha OHC), 7 beta-hydroxycholesterol (7 beta OHC), cholesterol 5 alpha,6 alpha epoxide (alpha epoxyC), cholesterol 5 beta,6 beta-epoxide (beta epoxyC), 7 ketocholesterol (7ketoC), 26-hydroxycholesterol (26OHC), cholesterol-3 beta,5 alpha,6 beta-triol (TriolC) and the possible protecting effect of vitamin E on 26OHC-induced cytotoxicity were investigated in smooth muscle cells isolated from the arteries of human umbilical cords. METHODS: To study the cytotoxicity of oxysterols, the cells were incubated with each oxysterol at a level of 10 micrograms/ml from 24 to 120 hours, then 45Ca++ uptake, cytosolic free Ca++ level, [3H]thymidine incorporation, total DNA content and viable cell number were measured. Cholesterol was used as a control. For tracing the possible origin of cytotoxicity of 26OHC, cholesterol, phospholipid and 26OHC content in the membrane were investigated from 24 to 72 hours. For determining whether antioxidants had a protective effect against the cytotoxicity of 26OHC, vitamin E and butylated hydroxytoluene (BHT) were used. RESULTS: The results indicated that the oxysterols elevated 45Ca++ uptake and cytosolic free Ca++ level, but diminished [3H]thymidine incorporation, total DNA content and viable cell number. 26OHC lowered the cholesterol content of the membrane and incorporated into the membrane after 24 hours of the incubation, but did not alter the total phospholipid content of the membrane until 72 hours. Neither vitamin E or BHT significantly protected the cells from the 26OHC-induced alterations. CONCLUSION: We suggest that the cytotoxicity of oxysterols, which might result in an alteration in Ca++ ion flow into the cell by decreasing cholesterol content and incorporating oxysterol itself into the membranes, could not be protected by vitamin E. PMID- 7790695 TI - Effects of long-term vitamin E supplementation in alcoholic cirrhotics. AB - OBJECTIVE: Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms. Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases. The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics. PATIENTS AND METHODS: 67 subjects were included in this double blind trial; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year. Each month, the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment. Every 3 months, the patients underwent a medical examination, and blood samples were taken for clinical laboratory analysis and serum vitamin E measurement. RESULTS: Alpha tocopherol levels were significantly lower in patients with more severe liver disease. This difference was not significant when vitamin E levels were corrected by cholesterol. Oral supplementation significantly increased serum vitamin E levels in the experimental group. Alcohol ingestion and hospitalization rates were similar in both groups. Life table analysis did not show significant differences in mortality between the two groups. DISCUSSION: Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters, mortality or hospitalization rates of decompensated alcoholic cirrhotics, although serum levels of the vitamin significantly increased. PMID- 7790694 TI - Marginal dietary protein restriction reduced nonprotein nitrogen, but not protein nitrogen, components of human milk. AB - OBJECTIVE: This study was designed to determine whether marginal dietary protein intakes of lactating women alter their milk production and composition. The study followed the observation that marginal dietary protein intakes lead to significantly negative nitrogen balances in these women. METHODS: Twenty-four healthy, mature lactating women were divided evenly into three groups on the basis of postpartum times; 1, 5, or 12 months. Each woman was given a controlled protein diet of either 1.5 (HP) or 1.0 (MP) g/kg body weight/day for 7 to 10 days. Milk production was measured for 72 hours by test weighing the infant before and after feeding. Milk samples from alternate breasts were collected for 24 hours, pooled, and analyzed for their protein nitrogen, nonprotein nitrogen, free and protein-bound amino acid, and lactoferrin concentrations. RESULTS: Reduced dietary protein intakes were associated with a decrease (p < 0.05) in the nonprotein nitrogen and total free amino acid fractions of milk. Although urea was unaffected, the concentrations of milk free leucine, phenylalanine, histidine, and ornithine were lower (p < 0.05) in the MP than in the HP group, while the output of leucine and histidine tended to be lower in the MP group. The amount of milk produced, as well as the amounts of protein nitrogen, protein bound amino acid, and lactoferrin and their concentrations were unaffected by a reduction of dietary protein. CONCLUSIONS: Maternal milk production and the protein nitrogen, but not the nonprotein nitrogen, fraction of human milk were relatively well-preserved in the presence of a short-term, marginal reduction of dietary protein. PMID- 7790693 TI - Dietary mustard, rape seed oils and selenium exert distinct effects on serum Se, lipids, peroxidation products and platelet aggregability. AB - OBJECTIVE: A degenerative cardiomyopathy (DCM) has been observed among mustard oil (MUST) users in China who eat 150 ml/week. Though the condition may be a selenium (Se) deficiency, MUST, rich in erucic acid (22:1), may bear a cardiotoxic or pro-oxidant substrate(s). The purpose of this feeding study was to compare the effects of feeding MUST, high erucic acid rape seed oil (HEAR), low erucic acid rape seed oil (LEAR) and corn oil, with or without Se addenda, on serum cholesterol, triglycerides, thiobarbituric acid reactive substances (TBARS), alpha-tocopherol, platelet aggregation and hepatic glutathione peroxidase (GSHPXase). Heart muscle pathology was evaluated. METHODS: Eighty male, weanling Wistar rats were divided into four dietary groups and fed AIN76A diet for 8 weeks with one of four oils: 1) MUST, 2) HEAR, 3) LEAR, or CORN oil. Half of each group received 0.43 mg/kg Se supplement. A purified diet was fed for 8 weeks. RESULTS: Neither Se nor oil type affected growth, though serum Se rose with dietary Se addendum (p < 0.01), and hepatic GSHPXase rose for each oil (p < 0.01). Se deprivation led to elevated serum cholesterol, except for the CORN oil group (p < 0.01). Only with LEAR did HDL cholesterol decrease. Serum triglycerides decreased with MUST and LEAR feedings (p < 0.05). In Se deficiency, HEAR led to elevated TBARS (p < 0.01), though not MUST, which contained twice as much alpha-tocopherol. Though supplementary Se protected the HEAR-fed animals from secondary peroxidation as TBARS (p < 0.01), the MUST group was not so protected. Ration Se also spared serum alpha-tocopherol for each diet group except the MUST/Se group (p < 0.05). MUST oil feeding resulted in increased platelet aggregation; MUST and HEAR resulted in increased platelet ATP release compared with CORN oil. CONCLUSION: Oxidative mechanisms may be involved in the DCM involving both Se limitation and pro-oxidant stress related to the usual intake of MUST. Human studies have been undertaken to test this thesis. PMID- 7790696 TI - Metabolic effect of parenteral nutrition in dogs with obstructive jaundice. AB - OBJECTIVE: To assess the effect of total parenteral nutrition (TPN) on macronutrient metabolism in obstructive jaundice. METHODS: Forty adult mongrel dogs were equally divided into four groups: group I (PO-control) received sham ligation of common bile duct (CBDL) and was fed dog chow and water ad libitum; group II (PO-CBDL) underwent CBDL and was fed dog chow; group III (TPN-control) received sham CBDL and TPN; and group IV (TPN-CBDL) underwent CBDL and received TPN. Blood chemistries, plasma amino acids and liver histologies were studied before (Day 1) and at the end (Day 14) of the experiment. RESULTS: A significant elevation of bilirubin and alkaline phosphatase was observed in dogs with CBDL. Blood glucose was not changed significantly in any group. Significant increases in triglyceride and cholesterol were present in CBDL dogs. Significant differences in the concentrations of a few plasma amino acids, including an elevation of phenylalanine, were found in TPN dogs. A significant increase in aromatic amino acids (AAA) and a noticeable depression of the molar ratio of branched-chain amino acids (BCAA) to AAA was present in TPN-CBDL dogs, as was a significant increase in blood ammonia. CONCLUSION: In the presence of obstructive jaundice, TPN does not significantly affect carbohydrate or lipid metabolism. However, a derangement in protein metabolism with the standard TPN solution in current use suggests that either a modification of amino acid composition or an increase in total energy to protein energy ratio in TPN solution may be necessary to obviate such a consequence. PMID- 7790698 TI - ISSFAL Board Statement: recommendations for the essential fatty acid requirement for infant formulas. International Society for the Study of Fatty Acids and Lipids. PMID- 7790697 TI - Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. AB - OBJECTIVE: Establish dietary-induced ketosis in pediatric oncology patients to determine if a ketogenic state would decrease glucose availability to certain tumors, thereby potentially impairing tumor metabolism without adversely affecting the patient's overall nutritional status. DESIGN: Case report. SETTING: University Hospitals of Cleveland. SUBJECTS: Two female pediatric patients with advanced stage malignant Astrocytoma tumors. INTERVENTIONS: Patients were followed as outpatients for 8 weeks. Ketosis was maintained by consuming a 60% medium chain triglyceride oil-based diet. MAIN OUTCOME MEASURES: Tumor glucose metabolism was assessed by Positron Emission Tomography (PET), comparing [Fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG) uptake at the tumor site before and following the trial period. RESULTS: Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression. CONCLUSION: While this diet does not replace conventional antineoplastic treatments, these preliminary results suggest a potential for clinical application which merits further research. PMID- 7790699 TI - Evidence of non-A, non-B, non-C infection in chronic hepatitis by polymerase chain reaction testing for hepatitis B and C viruses. AB - BACKGROUND/AIMS: Although hepatitis C virus is clearly the major cause of non-A, non-B acute and chronic hepatitis, there is a group of patients with histologically documented chronic hepatitis with no serological marker of hepatitis B and C, nor any other risk factors for liver disease. METHODS: We have investigated 17 well-characterized patients with chronic active hepatitis. HBV DNA and HCV-RNA were tested by polymerase chain reaction in 17 serum samples and in six liver biopsies. RESULTS: Four of the 17 patients had serum HCV-RNA detectable by polymerase chain reaction, while none had HBV-DNA detectable by polymerase chain reaction. Three of the six liver samples gave a positive signal by cyclin A and HLA, and only these were considered for the study. One of the three was HCV-RNA positive, while none was HBV-DNA positive. CONCLUSIONS: Our results, obtained through careful elimination of all known risk factors for liver disease, strongly suggest that non-A, non-B, non-C hepatotropic virus(es) could be involved in some cases of chronic active liver disease. PMID- 7790700 TI - Relationship between hepatitis C virus subtypes and clinical features of liver disease seen in alcoholics. AB - The influence of hepatitis C virus and its subtypes on the clinical course of liver disease in alcoholics was assessed. Hepatitis C virus infection was confirmed by a reverse transcription and polymerase chain reaction method for the hepatitis C virus NS-5 region in the sera of alcoholics with various stages of histologically proven liver disease. The frequency of hepatitis C virus was significantly higher in alcoholics with chronic hepatitis (73%) than in those with liver fibrosis (18%), alcoholic hepatitis (17%), and fatty liver (0%). Hepatitis C virus subtypes, namely K1 and K2, were determined by dot-blot hybridization analysis of the polymerase chain reaction products with specific probes, and their frequencies were 68% and 32%, respectively. The proportion of patients whose serum transaminase levels returned to normal following 4 weeks of abstinence in hospital was significantly lower in alcoholics with hepatitis C virus viremia (glutamic oxaloacetic transaminase: 53.8%; glutamic pyruvic transaminase: 42.3%) than in those without viremia (glutamic oxaloacetic transaminase: 86.2%, p < 0.01; glutamic pyruvic transaminase: 89.7%, p < 0.01). When alcoholics with the K1 and K2 subtypes of hepatitis C virus were compared, normalization of transaminase levels was less frequent in alcoholics with K1 (glutamic oxaloacetic transaminase: 42.8%; glutamic pyruvic transaminase: 28.6%) than in those with K2 (glutamic oxaloacetic transaminase: 88.9%, p < 0.05; glutamic pyruvic transaminase: 77.8%, P < 0.05). These data indicate that hepatitis C virus infection is associated with a reduced rate of recovery of serum transminase levels following abstinence in subjects with alcoholic liver disease, more so in the K1 subtype than in the K2 subtype. PMID- 7790702 TI - Bacterial expression and purification of hepatitis C virus capsid proteins of different size. AB - Two capsid sequences of the hepatitis C virus were cloned and expressed in an E. coli system. One sequence (c190) comprised the complete capsid region with 573 nucleotides. The other sequence (c125) spanned 375 5'-nucleotides lacking the hydrophobic 3'-part of the hepatitis C virus capsid gene. A full-length and a truncated construct were chosen, since it is not known whether there is 3' truncation of the hepatitis C virus capsid during protein maturation similar to the situation in some flaviviridae. The corresponding expression clones 190/4 and 125/4 were constructed by polymerase chain reaction cloning into pQE-vectors. The protein expressed, pc125, which is lacking the hydrophobic carboxyterminus of the full-length capsid protein pc190, showed a stronger signal in western blots using anti-hepatitis C virus/EIAII-positive patient's serum. This could be due to better expression and/or better solubilization of pc125. The truncated protein pc125 displayed the predicted molecular weight of 19 kD, whereas the full-length protein pc190 migrated faster than expected. This could be due to intracellular proteolytic processing, giving rise to a truncated protein or to an atypical mobility in SDS-PAGE gels caused by the hydrophobic nature of the full-length protein. Both proteins were synthesized with an aminoterminal tag of six histidines that could be used for purification by Nickel chelate affinity chromatography. The elution fractions of the two proteins showed additional bands in western blots. Most of these proteins had a mass between 2 and 16 kD and are likely to be degradation products. Protein pc125 could be purified in larger quantities than pc190.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790701 TI - Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. AB - To investigate the histological change (change of liver fibrosis) produced by the anti-viral effect of interferon on hepatitis C virus, 40 patients with chronic hepatitis C treated with natural interferon alpha were divided according to the existence of viremia at the end of treatment and 6 months after the end of treatment. The condition of liver fibrosis was scored numerically with a new "hepatic fibrosis score" which is sensitive to more subtle changes than Knodell's fibrosis score. Each portal zone was evaluated separately. End-of-treatment biopsy for the HCV RNA-negative group (negative for HCV RNA at the end of treatment) showed a significant improvement of the "hepatic fibrosis score" as well as the alleviation of necrosis and inflammation. At the end of treatment and 6 months after that, serum procollagen type III peptide levels and serum type IV collagen-7s levels had also decreased significantly in the HCV RNA-negative group. The present study showed that treatment with interferon alpha could alleviate fibrosis in addition to necrosis and inflammation. PMID- 7790703 TI - Histological and biochemical effects of cyclosporine A withdrawal from a triple drug regimen after over 2 years of treatment in liver transplant patients. AB - Cyclosporine A was withdrawn from a triple drug immunosuppressive regimen in 10 clinically and biochemically stable liver transplant patients. This study reports the effects of cyclosporine A withdrawal on liver tests and liver histology. Serum aspartate amino transferase and serum alanine amino transferase values increased significantly. Seven out of ten patients had histological changes after cyclosporine A withdrawal, but not before. These changes were compatible with acute rejection (consistent with rejection) in two patients and grade I also in two patients, including one patient with a second graft. Only two of these patients needed corticosteroid treatment (one consistent with rejection and one grade I rejection). Cyclosporine A treatment was restarted in three patients, because a coexisting osteoporosis prohibited prolonged corticosteroid recycling. Seven patients were able to maintain stable though slightly elevated transaminases without cyclosporine A, with a follow up of median 26 months. Our results suggest that in stable patients cyclosporine A withdrawal can be considered, for instance 2 years after liver transplantation. PMID- 7790705 TI - Effect of propranolol on portosystemic collateral circulation estimated by per rectal portal scintigraphy with technetium-99m pertechnetate. AB - BACKGROUND/AIMS: Propranolol is widely used in the prevention of variceal bleeding. However, in certain patients with cirrhosis, the portal hypotensive effect of propranolol cannot be obtained. An explanation for portal unresponsiveness to propranolol could be an increase in portocollateral vascular resistance mediated by this drug. METHODS: In 33 patients with cirrhosis the effect of chronic administration of propranolol on portocollateral blood flow from the inferior mesenteric vein was examined by means of per-rectal portal Tc 99m pertechnetate scintigraphy. RESULTS: Propranolol significantly reduced the shunt index by 15.3 +/- 4.2%. This reduction was observed only in patients with cirrhosis classified as Child-Pugh A and B groups, but not group C. Differences between groups in portosystemic shunt index changes after propranolol were significant (F = 3.4, p < 0.05). CONCLUSIONS: The data presented suggest that propranolol changes the distribution of blood between the portal and systemic circulation, which is probably due to the increase in vascular resistance of portocollateral vessels. The magnitude of the vascular response to propranolol depends on the severity of liver disease. PMID- 7790704 TI - Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. AB - Plasma endotoxin levels were investigated using a quantitative Limulus assay in patients with chronic liver diseases and correlated with the severity of liver diseases, the presence of esophageal varices, and hemodynamic parameters. The plasma endotoxin levels were significantly higher in chronic hepatitis patients with acute exacerbation (10.1 +/- 1.3 pg/ml, n = 13, p < 0.05) and patients with cirrhosis (7.0 +/- 0.7 pg/ml, n = 126, p < 0.05) than in healthy subjects (2.9 +/ 0.2 pg/ml, n = 45). Chronic hepatitis patients (n = 30) had plasma endotoxin levels which were similar to those in healthy subjects (4.6 +/- 0.5 vs. 2.9 +/- 0.2 pg/ml, p > 0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6 +/- 0.5 vs. 10.1 +/- 1.3 pg/ml, p < 0.05). Endotoxemia (plasma endotoxin level > 5.7 pg/ml) was found in 27%, 85% and 41% of patients with chronic hepatitis, chronic hepatitis with acute exacerbation, and cirrhosis, respectively. In patients with cirrhosis, the plasma endotoxin levels progressively increased in relation to the severity of liver dysfunction (Pugh's class A/B/C = 4.9 +/- 0.5/7.9 +/- 1.4/10.2 +/- 2.0 pg/ml, p < 0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhosis with and without esophageal varices (p > 0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhosis and large varices (p < 0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790706 TI - Aminopyrine breath test improves long-term prognostic evaluation in patients with alcoholic cirrhosis in Child classes A and B. AB - In a 4-year survival study, we evaluated the prognostic value of the aminopyrine breath test and the Child-Turcotte-Pugh score in 190 alcoholic patients. Using aminopyrine breath test results, the patients were stratified into group 1 (aminopyrine breath test > 2%), group 2 (1% < or = aminopyrine breath test < 2%) and group 3 (aminopyrine breath test < 1%). Survival rates at 4 years were 68% in group 1, 35% in group 2 and 17% in group 3. Using the Child-Turcotte-Pugh score, survival rates at 4 years were 67% in Child-Turcotte-Pugh class A, 40% in class B and 7% in class C. To assess the value of aminopyrine breath test as an adjunct to Child-Turcotte-Pugh score in prognostic evaluation of patients with cirrhosis, two approaches have been used: a regression analysis using Cox's proportional hazard model by including the Child-Turcotte-Pugh score and aminopyrine breath test value, and the log-rank test to assess the prognostic value of aminopyrine breath test in each Child-Turcotte-Pugh class separately. The regression analysis showed that both parameters, the Child-Turcotte-Pugh score and the aminopyrine breath test results, were accepted in the model, suggesting that the aminopyrine breath test was still significantly related to survival once the Child-Turcotte Pugh score had been entered into the model. Analysis of the prognostic value of the aminopyrine breath test in each Child-Turcotte-Pugh class separately indicated, however, that the contribution was negligible in the Child-Turcotte Pugh class C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790708 TI - Aminoglycoside-associated nephrotoxicity in extrahepatic obstructive jaundice. AB - Experimental data demonstrate that biliary obstruction increases renal sensitivity to gentamicin. In the present study the incidence of and risk factors for aminoglycoside nephrotoxicity were prospectively studied in patients with extrahepatic obstructive jaundice. Two hundred and thirty-seven hospitalized adult patients were classified into three groups. Group I consisted of 84 patients with extrahepatic obstructive jaundice, who received aminoglycoside (gentamicin or tobramycin). Group II consisted of 81 patients with extrahepatic obstructive jaundice, who received either antibiotics other than aminoglycoside or no antimicrobial therapy. Group III consisted of 72 noncholestatic patients receiving aminoglycosides for different disorders. Nephrotoxicity developed in 27 patients (32%) in group I vs 9 patients (11%) in group II and 4 patients (5.6%) in group III (p < 0.00001). In group I, a comparison of patients with and without nephrotoxicity revealed significantly higher values in the former for mean serum bilirubin concentration, initial steady-state trough aminoglycoside concentration and estimated half-life. Stepwise multivariate analysis with nephrotoxicity status as the dependent variable determined that the most significant variable for predicting nephrotoxicity was serum total bilirubin level. In extrahepatic cholestasis a high serum bilirubin level is a distinct factor predisposing to aminoglycoside nephrotoxicity. PMID- 7790707 TI - Vasodilatory effects of propylthiouracil in patients with alcoholic cirrhosis. AB - BACKGROUND/AIMS: An experimental study has shown that propylthiouracil increases portal blood flow in normal rats. Whether propylthiouracil has a similar effect in patients with alcoholic cirrhosis remains to be demonstrated. The aim of this study was to evaluate the effects of oral propylthiouracil (300 mg) on systemic and portal hemodynamics in patients with alcoholic cirrhosis. METHODS: Plasma propylthiouracil levels were also measured by high performance liquid chromatography in five patients with alcoholic cirrhosis. In eight patients with cirrhosis, mean arterial pressure, cardiac output and portal blood flow were evaluated before and after placebo and propylthiouracil administration. Hemodynamic measurements were performed by the Doppler technique. The plasma peak level of propylthiouracil was achieved at 1.4 +/- 0.1 h in patients with alcoholic cirrhosis. This time was chosen to express hemodynamic changes. RESULTS: Propylthiouracil administration caused a significant increase in portal blood flow (+16.5%, p < 0.05) in patients with alcoholic cirrhosis. This effect was associated with a mild and significant rise in cardiac output (from 5.8 +/- 0.2 to 6.1 +/- 0.3 l/min, p < 0.05) and a decrease in peripheral vascular resistance (from 1171 +/- 69 to 1070 +/- 67 dyn . s-1 . cm-5, p < 0.01). A significant correlation was observed between changes in portal blood flow and peripheral vascular resistance (r = 0.79, p < 0.05). No significant changes were observed after placebo. CONCLUSIONS: Our findings show that propylthiouracil has a vasodilatory effect in patients with alcoholic cirrhosis. We postulate that this effect could be the mechanism by which propylthiouracil decreases hypermetabolic state, and increases oxygen delivery to the liver, in patients with alcoholic liver diseases. PMID- 7790709 TI - Pattern of bile acid regurgitation and metabolism during perfusion of the bile duct obstructed rat liver. AB - Bile acid processing in the long-term, bile duct obstructed rat liver was studied ex vivo. Twenty four and 72 h, respectively, after bile duct obstruction the isolated liver was perfused with taurodeoxycholate (16 nmol/min per g liver) the bile duct still being closed. Uptake, metabolism and regurgitation profile were traced by bolus injection of tritium-labeled bile acid; in addition, concurrent histological changes were examined by light- and electron microscopy. Ligation caused dilatation of the intrahepatic ductular branches and increased the serum bile acid concentration to 740 +/- 75 microM (controls: 16 +/- 2.12), reaching its maximum within 24 h. At 16 nmol/min per g liver uptake rate was > 96% in controls and in bile duct obstructed rats. Maximal uptake rates (assessed separately) differed between controls and bile duct obstructed rats (700 nmol/min per g liver vs. 460). Controls excreted more than 80% of labeled bile acid in bile within 10 min after bolus injection. Biliary recovery of label was virtually completed after 30 min. In bile duct obstructed rats excretion of label back to the perfusate effluent (regurgitation) started quantitatively 5 min after bolus application and peaked between 10 and 40 min; after 80 min, effluent recovery was incomplete (about 60% of bolus injected). Biliary bile acids of controls consisted of about 20% taurodeoxycholate-metabolites; bile acids in the perfusate effluent of bile duct obstructed rats of about 55%. The major metabolite in all animal groups was taurocholate; minor metabolites were tauroursocholate, tauro-3 alpha,7 = 0,12 alpha-cholanoic acid and 3-sulfo-taurodeoxycholate. Histologically, inflammation and periportal edema were present after 1 day of bile duct obstruction. After 3 days, marked proliferation of bile ductules was the dominant histological feature. It is concluded that during initial bile duct obstruction, bile acid processing is not altered, although ultrastructural alterations occur early. PMID- 7790710 TI - Induction of chronic cholangitis in the rat by trinitrobenzenesulfonic acid. AB - We investigated the effects of the hapten trinitrobenzenesulfonic acid instilled into the rat biliary tree. The study included three groups of animals that received a single intracholedochal injection of either saline, 10% ethanol or 10 mg trinitrobenzenesulfonic acid dissolved in 10% ethanol. A fourth group of rats was subjected to common bile duct ligation and was used as control for biliary obstruction. Liver and biliary tract dysfunction was assessed 1, 10, 20 and 30 days after treatment by serum aspartate aminotransferase, alkaline phosphatase and bilirubin, and by histopathological examination of liver slices. By day 10, saline- or ethanol-treated rats did not show changes in the biochemical parameters, and light microscopy revealed no alterations. In contrast, rats treated with trinitrobenzenesulfonic acid showed significant increases in all serum markers throughout the study period. Inflammatory cell infiltrates were seen in portal areas and around bile ducts, indicating pericholangitis. Some rats presented with dilatation of extrahepatic biliary ducts; ductal proliferation and thin porto-portal fibrotic septa were observed in these cases. Bile duct ligation also induced ductal proliferation and fibrosis in all cases, but pericholangitis was not prominent. Retrograde cholangiograms in trinitrobenzenesulfonic acid rats showed distortion of the intra- and extrahepatic biliary tree. In conclusion, chronic cholangitis may be consistently induced in rats by a single intracholedochal administration of trinitrobenzenesulfonic acid. PMID- 7790712 TI - Loss of heterozygosity in liver tumours. PMID- 7790711 TI - Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. AB - BACKGROUND/AIMS: Kupffer cells are involved in local immunoregulation in the liver by secretion of cytokines and direct cellular contact. They are able to influence the function of other liver cells, i.e. sinusoidal endothelial cells, Ito cells and hepatocytes. The three known major functions of Kupffer cells are clearance of endotoxin from the portal circulation, release of soluble mediators and presentation of antigen. METHODS: Human Kupffer cells were isolated by collagenase perfusion followed by centrifugal elutriation and analyzed for cytokine secretion after 3 days in culture. RESULTS: We found that freshly isolated human Kupffer cells secreted the anti-inflammatory cytokine interleukin 10 in response to stimulation with lipopolysaccharide. The release of interleukin 10 was maximal 12-24 h after lipopolysaccharide challenge. Furthermore, we could show that exogenous interleukin-10 downregulated the release of the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha by Kupffer cells after lipopolysaccharide stimulation. The release of interleukin-6 was maximal 24 h after stimulation and interleukin-10 inhibited interleukin-6 release after 6 h. Tumor necrosis factor alpha showed maximal secretion 6 h after stimulation and exogenous interleukin-10 also downregulated the tumor necrosis factor alpha release after 6 h. CONCLUSIONS: Kupffer cells are exposed physiologically to lipopolysaccharide present in portal venous blood. Given the known anti-inflammatory effect of interleukin-10, our findings of secretion of interleukin-10 by Kupffer cells in response to lipopolysaccharide and suppression of interleukin-6 and tumor necrosis factor alpha release by Kupffer cells in vitro through exogenous interleukin-10 suggest an important role for interleukin 10 in the regulation of the local immune response in the liver sinusoid. PMID- 7790713 TI - Biliary cholesterol transport and the nucleation defect in cholesterol gallstone formation. PMID- 7790715 TI - Correlation of HCV-RNA levels in serum and liver of patients with chronic hepatitis C. PMID- 7790714 TI - Somatostatin or octreotide versus endoscopic sclerotherapy in acute variceal haemorrhage: a meta-analysis study. PMID- 7790716 TI - Augmented endogenous nitric oxide production in partial portal vein-ligated rats. PMID- 7790717 TI - Cytolytic hepatitis with a venotonic drug. PMID- 7790719 TI - Domestic violence: a health concern. AB - Domestic violence may be the single most common etiology for injuries in women presenting to the health care system. There is a national effort to begin to ask all female patients about family violence. Physicians have a responsibility to identify, educate and appropriately manage and/or refer patients in violent relationships. PMID- 7790718 TI - State asks doctors to help test for lead. Interview by Bob Carlson. PMID- 7790721 TI - Trends in laparoscopic cholecystectomy in Indiana. AB - Laparoscopic cholecystectomy is a fairly new procedure that is quickly gaining widespread use among surgeons. In Indiana, 45% of cholecystectomies performed on Medicare beneficiaries over the age of 65 were via the laparoscopic approach, resulting in a shorter average length of stay, 5.9 days, compared to 12.3 days for those who underwent the open procedure. Among these Medicare beneficiaries, the complication rate for laparoscopic cholecystectomy was lower than for those who had the open procedure, 11.3% compared with 16.6%. The trend of the use of the laparoscopic approach for cholecystectomy for older patients and the complications arising from this procedure need further evaluation. PMID- 7790720 TI - Physician-assisted suicide and euthanasia: a house staff debate. PMID- 7790722 TI - Exhibit explores development of sports medicine. PMID- 7790723 TI - Secretion capture and report web: use of affinity derivatized agarose microdroplets for the selection of hybridoma cells. AB - A novel assay is described which allows the entrapment and detection of the immunoglobulin secreted from individual viable hybridoma cells using a secretion capture and reporter web (SCRW). By encapsulating the cells in agarose microdroplets which have been derivatized to create a fluorescent antigen specific sandwich assay, flow cytometry can be used to identify and sort productive cells from a heterogeneous population. Using agarase, the cells can be recovered from the microdroplets and clonally expanded after selection. The assay has been used to reclone rare secretors from hybridoma cultures and to enhance the production of cultures with poor producers. The assay is easily generalized for the detection of any secreted protein for which specific antibodies or other ligands are available. PMID- 7790724 TI - A novel method to purify immunotoxins from free antibodies using modified recombinant toxins. AB - Monoclonal antibodies linked to toxin polypeptides (immunotoxins) are developed for clinical application against cancer and graft rejection. Immunotoxins prepared by many conventional methods often contain a trace amount of free antibody. Present studies describe a method to purify immunotoxins from free antibody in conjugation mixtures. Recombinant ricin A chain and a truncated form of diphtheria toxin (385 residues) containing ten consecutive histidine residues at the amino terminus were prepared. The modified toxin polypeptides retaining full biological activity were chemically linked to monoclonal antibodies (317G5 and 454C11) reactive to breast cancer cells. The high affinity of consecutive histidine residues for nickel-based resin (Ni-NTA) was exploited to purify immunotoxins from unreacted free antibodies. SDS-PAGE analysis of conjugates eluted from nickel column contained trace amounts of detectable free antibody whereas conjugates purified by other conventional methods using phenyl Sepharose or Cibacron blue Sepharose chromatography contained significant amounts of unconjugated antibody. Furthermore, the immunotoxin fraction containing predominantly two toxin molecules linked to one antibody can be separated from stoichiometric conjugates by Ni-NTA column. Cytotoxicity experiments showed that the complex of two toxin molecules linked to an antibody was more cytotoxic to tumor cells in vitro than the fraction enriched with immunotoxin containing equimolar stoichiometry. PMID- 7790725 TI - In vitro proliferative responses of human peripheral blood mononuclear cells to non-recall antigens. AB - Primary in vitro proliferative responses of naive T cells to antigens other than superantigens and alloantigens have been little studied. Two tissue culture techniques have been reported which support in vitro antigen priming of T cells. These methods require various degrees of cellular manipulation and culture vessels other than standard microtitre plates. We report here that primary proliferative responses to non-recall antigens can be readily obtained using unselected human PBMC prepared from either adult or cord blood. Cells proliferate whether cultured in 2 ml volumes, 200 microliters microcultures or 20 microliters hanging drops. The variation in the proliferative responses increases as the culture volume is decreased such that considerable errors are apparent when Terasaki culture plates are used. The lowest stimulation indices are also observed in the 20 microliters microcultures. Nevertheless, similar response patterns are noted for the differing culture vessels; generally, proliferative responses reach peak magnitude only after 7 days of culture. The initial concentration of PBMC in culture influences the magnitude of the reactions such that halving the cell numbers frequently leads to greater than 50% reduction in the measured responses. The results of this study indicate that neither a specialised culture vessel nor complex cellular manipulation are required for in vitro priming of T cell immunity. Consequently, this area of immunology should be readily amenable to further study. PMID- 7790726 TI - Elution of human IgG from affinity columns containing immobilised variants of protein A. AB - Immobilised analogues of protein A have been used for affinity chromatographic separation of human IgG. Truncation of the C-terminal region of an engineered IgG binding domain based upon the B domain from protein A, in combination with site directed mutagenesis, has led to the generation of a number of proteins with a decreased affinity for IgG. The elution of human IgG from these proteins when immobilised onto a solid support occurs over the pH range 3.2-5.0 with 0.5 M acetate buffer. These proteins may be effective alternatives to standard protein A columns when milder elution conditions are required. PMID- 7790727 TI - Efficient isolation of mutant antigen presenting cell lines by functional selection using T cell clones. AB - An efficient method for the isolation of mutant antigen-presenting cell (APC) lines is described. When mixtures of transfectant APC lines TA beta z (that express A beta z/A alpha d MHC class II molecules) and hypothetical variant APC lines TA beta d (that express A beta d/A alpha d class II molecules) were cultured with and selected by autoreactive A beta z/A alpha d-restricted T cell clones, the percentage of TA beta d APC lines increased from less than 1% of the original APC mixtures to almost 100% after several cycles of selection. This increase of hypothetical variant was shown to be due to the formation of aggregates of wild-type TA beta z APC lines with A beta z/A alpha d-restricted autoreactive T cell clones that results in the inhibition of proliferation and probably killing of TA beta z APC lines. Based on this, ethyl methane sulfonate (EMS)-treated TA beta z APC lines or B-B hybridoma APC lines MW4 (that express A beta z/A alpha d and A beta z/A alpha z class II molecules) were cultured with and selected by A beta z/A alpha d-restricted autoreactive T cell clones to obtain mutant APC lines that escaped the recognition by T cell clones. After cloning, about 43% of clones examined lost the ability to stimulate T cell clones with concomitant loss of class II molecule expression. Less than 1% showed loss of stimulatory activity against T cell clones in spite of the expression of normal amounts of class II molecules. Initial analysis revealed that they include APC mutant lines with (1) altered MHC class II sequences, (2) loss of adhesion molecule expression and (3) possible impairment of the peptide loading. The method described here may provide a variety of mutant APC lines that are useful for the analysis of antigen processing and presentation pathways as well as of class II structure for T cell stimulation. PMID- 7790728 TI - The derivation of binding parameters from effector and target conjugate frequency data using linear and non-linear data-fitting transformations. Application of such transformations to the NK-MOLT4 and NK-K562 effector-target systems. AB - Effector-target conjugation is described quantitatively by binding isotherms which are characterized by three parameters, the maximum effector and target conjugate frequencies, alpha max and beta max, and the dissociation constant of the conjugates formed, KD. In this paper the application of non-linear data fitting techniques, as well as linear transformations of the binding isotherms that permit us to use standard regression analysis, has been tested to calculate estimates of these parameters in the NK-MOLT4 and NK-K562 effector-target systems. Both unweighted and weighted data were used to calculate alpha max, beta max and KD for six different donors which were used as a source of NK cells. The results obtained have shown that these regression methods are useful for revealing potential disparities between binding efficiencies in effector-target systems. PMID- 7790729 TI - Cytokine immunotrapping: an assay to study the kinetics of production and consumption or degradation of human interferon-gamma. AB - With the aim of determining the rate of cytokine production, we have investigated immunoassay conditions which prevent consumption/degradation. These assays, termed cytokine immunotrapping assays (CITA), are based on early capturing of cytokines secreted during cell culture by immobilised or soluble mAbs and a recently described chemiluminescent immunoassay. Here we describe assay conditions using IFN-gamma as a prototype cytokine. For production of IFN-gamma, PBMC, purified CD4+ or CD8+ T cells, or diluted whole blood were cultured with different T cell stimulating agents. Polystyrene macrobeads precoated with an anti-IFN-gamma mAb were put in culture and after a defined incubation period, a dimethyl acridinium ester (DMAE)-labelled second anti-IFN-gamma mAb and sodium azide were added into the culture for additional 24 h. The beads were washed and chemiluminescence signals determined in a luminometer. Trapping experiments were also performed with the beads or the soluble mAbs alone. Irrespective of the configuration, IFN-gamma concentrations measured in trapping conditions were always higher (3-20-fold) than in conventional cultures. By using the best trapping combination, i.e. both bead-mAb1 and DMAE-mAb2 added at the start of culture (single step), it was possible to detect IFN-gamma production as early as 2 h. Also, IFN-gamma secreted by less than 500 PBMC or whole blood cells could be detected within 24 h. When purified CD4+ or CD8+ cells were used instead of PBMC, a reduction of the trapping effect was observed. Conversely, addition of monocytes to purified T cells increased the trapping factor suggesting that a substantial amount of IFN-gamma was consumed or degraded both by CD14+ cells as well as T cells in culture. Preliminary results show that this assay is also suitable for the early detection of IL-1 and IL-4 which are known to be more tightly regulated. Thus, the new principle described here is expected to be useful in clinical settings where both the time and amounts of material are limited to investigate the role of cytokines in particular disease. PMID- 7790730 TI - Clinical implementation of electrical impedance tomography with hyperthermia. AB - We describe the use of electrical impedance tomography (EIT) for non-invasive thermal imaging in conjunction with a clinical treatment of a superficial scalp lesion utilizing a spiral microstrip antenna. This is our first reported use of EIT with a clinical hyperthermia treatment and perhaps the first world-wide. The thermal measurements recorded during treatment compare favourably with the images reconstructed from impedance data gathered during heating. A linear relation, measured in phantom material, between the change in temperature with the change in reconstructed impedance was assumed. The average discrepancy between the measured temperature changes with the temperatures reconstructed from the impedance changes was 1.4 degrees C, with the maximum being 8.9 degrees C. These preliminary data suggest that impedance changes can be measured during hyperthermia delivery and temperature estimates based on these observed changes are possible in the clinical setting. These findings also point to the complex, yet critical nature of the impedance versus temperature relationship for tissue in vivo. The reconstructed thermal images may provide complementary information about the overall thermal damage imposed during heating. Based on this initial clinical experience we feel that EIT has great potential as a viable clinical aid in imaging the temperature changes imposed during hyperthermia. PMID- 7790731 TI - Clinical, physiological and anatomical determinants for radiofrequency hyperthermia. AB - Temperature/time curves and corresponding CT scans of > 200 regional heat treatments with the hyperthermia system BSD-2000 in 43 patients have been analysed. In vivo variables and treatment parameters such as local specific absorption rate SAR, local relative SAR parallel SAR parallel, total power P, local cooling coefficients wb, and local steady-state temperature elevations delta Tss (above systemic temperature) have been determined. For determination of wb the well-known and accepted steady-state approach has been used, which was slightly modified for the purposes of this study. Specifically, comparison of cooling coefficients at the beginning and end of heat treatments were performed in tumours and normal tissues. Other variables are anatomical descriptors from CT scans, score of side effects plim, and various clinical factors. A variance analysis of the dependent variables, specifically delta Tss and parallel SAR parallel, is performed with respect to factors which were estimated as predictive. The intratumoral steady-state temperature elevations are determined by the perfusion-related cooling coefficients and local SAR to almost the same extent. Increase of cooling coefficients in tumours during the heat treatment characterizing the thermoregulatory potential have a slight but less important influence with respect to the achieved temperature elevations. SAR is influenced by several anatomical factors which determine the relative SAR distribution and clinical factors which limit the total power P. However, options for controlling present RHT systems in order to optimize the relative SAR distribution or to avoid hot spot phenomena appear limited. Three-dimensional modelling calculations show that the spatial arrangement of electrical interfaces emerging from bone and fat structures limits SAR control in available RHT technology and is mainly responsible for local power-dependent discomfort (Wust et al. 1994b). Some conclusions are drawn, about how technological development of hyperthermia technology can contribute towards overcoming this problem. PMID- 7790733 TI - Regional hyperthermia of pelvic tumours using the Utrecht 'Coaxial TEM' system: a feasibility study. AB - Between August 1989 and July 1992 a total of 22 patients (64 treatments) with inoperable or recurrent deep seated pelvic tumours were treated with regional hyperthermia and radiotherapy. The 70 Mhz Coaxial TEM applicator with its characteristic open waterbolus was used as heating device. The main objective of this pilot study was to evaluate the feasibility, toxicity and temperature data. The results showed that the major treatment limiting factors were insufficient power and systemic stress. Local pain was observed in only 10% of all treatments. Most of the treatments resulted in elevated systemic temperatures with the overall mean maximum oesophagus temperature reaching 38.9 +/- 0.7 degrees C, however, in only 6% of these treatments this was found to be treatment limiting. From the measured data the following intratumoral temperatures were calculated: T90 = 39.9 +/- 1.0 degrees C; T50 = 40.7 +/- 1.0 degrees C; T10 = 41.4 +/- 1.0 degrees C. In addition, the overall mean average normal tissue temperatures were determined: Trectum = 40.8 +/- 0.7 degrees C; Tvagina = 41.3 +/- 0.9 degrees C; Turethra = 40.8 +/- 0.9 degrees C. The temperatures in normal tissue were frequently higher than in tumour, indicating that a large volume was heated. The open waterbolus allows strong cooling, but the strategy was changed during the study: higher systemic temperatures were allowed to improve the pelvic temperatures. This pilot study proved that the open waterbolus is clinically a success, because it offers patient comfort and SAR-steering by patient repositioning, and that regional hyperthermia with the Coaxial TEM is feasible. PMID- 7790732 TI - Efficacy of indomethacin pretreatment with regional hyperthermia for treating upper abdominal malignancies. AB - It is important to reduce a systemic stress during regional hyperthermia against upper abdominal malignancies. A 50 mg indomethacin suppository was administered to five patients with intrahepatic tumour 30 min before hyperthermia. Oral temperature only rose to 37.8 degrees C, heart rate increased to just 110/min, and systolic blood pressure only increased to 134 mmHg. Under these conditions, epinephrine and norepinephrine rose to only 0.09 and 0.25 ng/ml, respectively, which were within normal limits. In addition, prostaglandin E2 (PGE2) did not increase at all. However, when these same five patients were not pretreated with indomethacin, parameters monitoring the systemic condition rose profoundly during hyperthermia. Systemic stress during hyperthermia against upper abdominal malignancies was reduced by the indomethacin pretreatment. PMID- 7790734 TI - Large stationary microstrip arrays for superficial microwave hyperthermia at 433 MHz: SAR analysis and clinical data. AB - Superficial hyperthermia with present day applicators provides a challenge when tumours exceed several cm in diameter. Unless microstrip applicators are scanned, the usable heat region often falls short of treating the entire region with 50% power or specific absorption rate (SAR). New microstrip applicator designs were evaluated through SAR analysis and compared to the traditional microstrip applicators used in the clinic at Dartmouth over the past six years. The new designs included fabricating thin archimedean spirals (1.0 mm strip width) incorporating dielectric substrate (epsilon = 5.3-10.8). The designs were optimized at 433 MHz for an arm length of 59 cm. Measurements in a plane 1.0 cm from the surface showed that thin spirals outperformed traditional designs by increasing the 50% SAR area by a factor of 2.5, while maintaining the same physical size. Arrays of four elements were fabricated from thin spirals, although SAR evaluation showed only 10-20% SAR between elements. Since this was deemed unacceptable and the design goal was to fabricate a stationary applicator that had at least 50% SAR between elements, dual element designs were created with gradually overlapped elements. It was found that overlapping three coils of the spiral created a large region that equalled or exceeded 50% SAR that could not be matched by single applicators. Coherent operation of the dual spiral array resulted in more central power deposition and incoherent operation resulted in more peripheral power deposition. SAR measurements at the fat/muscle interface showed an elongated heating pattern in hydroxyethylcellulose muscle equivalent phantom. Power deposition 1.0 cm deep in muscle retained the same basic size and shape with or without the fat layer. Patient treatments for chestwall tumours confirmed that the dual overlapping applicator heated a larger region without the sharp temperature peak associated with single applicators. PMID- 7790735 TI - Extracellular pH distribution in human tumours. AB - Extracellular pH (pHc) was determined by needle microelectrodes in 67 tumour nodules in 58 patients. The objective was to evaluate the relationship between pHe, tumour histology and tumour volume. The mean age of the patients was 62 years, mean depth of the lesions was 2.7 +/- 0.2 cm, and mean tumour volume was 187 +/- 60 cm3. Lesions were located in readily accessible areas such as on the limbs, neck or chest wall. Tumour histologies included: 48% adenocarcinoma; 34% squamous cell carcinoma; 8% soft tissue sarcoma; and 10% malignant melanoma. The mean tumour pHe for the entire group of tumours was 7.06 +/- 0.05 (range 5.66 7.78). Variation in pHe measurements between tumours was greater than the variation in measurements within tumour (F = 7.11, p < 0.01). In adenocarcinomas pHe was 6.93 +/- 0.08 (range 5.66-7.78), in soft tissue sarcomas 7.01 +/- 0.21 (6.25-7.45), in squamous cell carcinomas 7.16 +/- 0.08 (6.2-7.6), and in malignant melanomas 7.36 +/- 0.1 (6.98-7.77). Tumour pHe was significantly different between the four histological groups (p < 0.001). When adenocarcinoma and soft tissue sarcoma lesions were grouped together, pHe was 6.94 +/- 0.08 compared with 7.20 +/- 0.07 in squamous cell carcinomas and malignant melanomas lesions (p < 0.01). Tumour pHe increased as a function of the logarithm of tumour volume at 0.07 +/- 0.02 pH unit/ln cm3 (p = 0.006, r = 0.34). In conclusion, tumour histology and tumour volume were the most important factors determining the range of pHe's.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790736 TI - Response of 145 spontaneous canine head and neck tumours to radiation versus radiation plus microwave hyperthermia: results of a randomized phase III clinical study. AB - The results of a phase III, clinical trial of local microwave hyperthermia (target = 2 x 44 degrees C for 30 min) and megavoltage radiation (4 x 9 Gy fractions) in the treatment of 145 naturally occurring canine head and neck cancers are reported. Patients were re-examined at regular intervals following treatment until death. The median follow up time was 90 weeks. Tumour response, patient survival and normal tissue toxicity were analysed by treatment allocation. There was no significant difference in best tumour response nor patient survival between the two treatment groups. There was no difference in acute normal tissue toxicity but there was a suggestion that patients receiving RT and HT may suffer a higher incidence of late skin reactions. Histological type and tumour volume were of prognostic significance with smaller tumours and carcinomas showing higher response rates. There were also positive associations between minimum tumour dose and best tumour response and percentage of tumour heated and best tumour response. The results of this study must be interpreted in the knowledge of limitations on the dose and fractionation schedule for radiation therapy, the small number of hyperthermia treatments applied and the variation in tumour type and size that is inevitable in a clinical study. It is concluded that the quality of hyperthermia in terms of intra-tumour temperatures and the uniformity of heating is of paramount importance in governing response to adjuvant hyperthermia. PMID- 7790737 TI - Effects of step-down and step-up heating on the development of thermotolerance in a C3H mammary carcinoma in vivo. AB - The effects of step-down (SDH) and step-up heating (SUH) on the development of thermotolerance were investigated in a C3H mammary carcinoma in vivo. The endpoint was tumour growth time, i.e. the time for a tumour to reach a volume five times that of the first treatment day. SDH consisted of 44.5 degrees C/5 min followed immediately by 41.0 degrees C/120 min. SUH consisted of the same heat treatments but in reverse sequence. Thermotolerance was detected by subsequent heating at 43.5 degrees C at variable intervals following the primary SDH or SUH. The degree of thermotolerance was quantified by the thermotolerance ratio (TTR) calculated as a ratio between the slope of the dose-response curve for tumours heated at 43.5 degrees C and tumours preheated with either SDH or SUH followed by 43.5 degrees C. Both SDH and SUH induced thermotolerance. However, the maximal degree of thermotolerance and the time interval to reach maximum thermotolerance were different. For SUH maximal thermotolerance was observed at 8 h with a TTR of 3.6. For SUH, thermotolerance peaked at 24-28 h with a TTR of 7.3. In both cases thermotolerance had decayed with a 120 h interval. The SDH priming induced about 2.5 times more heat damage than SUH. The results are therefore in agreement with previous data obtained in the same tumour model by single heating showing that both the degree and the time to reach maximal thermotolerance increases with pretreatment heat damage. In addition, the results indicate that thermotolerance and thermosensitization are independent phenomena. PMID- 7790738 TI - Changes in microregional perfusion, oxygenation, ATP and lactate distribution in subcutaneous rat tumours upon water-filtered IR-A hyperthermia. AB - The effect of hyperthermia on microcirculatory and metabolic parameters in s.c. DS-sarcomas of different sizes on the hind foot dorsum of SD-rats was investigated. Hyperthermia was carried out using a novel water-filtered, infrared A radiation technique. Heating was performed at a rate of 0.5 degrees C/min until 44 degrees C was achieved in the tumour centre, which was maintained for 60 min. Using a multichannel laser Doppler flowmeter, red blood cell flux could be assessed continuously and at several sites within the tumour tissue simultaneously. Substantial inter-site variations in laser Doppler flux (LDF) were observed during hyperthermia which were independent of tumour size, site of measurement, and temperature at the site of measurement, indicating that single site measurements of tumour LDF are poor predictors of the mean response of a tumour to hyperthermia. When mean LDF was considered, decreases in red blood cell fluxes occurred that were more pronounced the greater the tumour volume. In no case was vascular stasis observed. Hyperthermia did not affect tumour oxygenation substantially. Microregional and global assessment of lactate and ATP concentrations demonstrated increased lactate and decreased ATP levels following hyperthermia. Tumour glucose levels were increased following hyperthermia, possibly due to an enlarged distribution space resulting from development of interstitial oedema. Changes in lactate and ATP levels and the lack of changes in tumour oxygenation suggest a modification of energy metabolism following hyperthermia in the form of increased ATP hydrolysis, intensified glycolysis and impaired oxidative phosphorylation. PMID- 7790740 TI - Application of the time-dependent Green's function and Fourier transforms to the solution of the bioheat equation. AB - A theory for solving the bioheat equation is developed using a time-dependent Green's function and Fourier transform techniques. The description of both steady state and time-dependent data are placed into a single framework which can also describe the effects of inhomogeneous blood perfusion. The theory is illustrated by examples including the modelling of a thermal conduction hyperthermia system and a new RF interstitial system. A possibility for measuring the blood perfusion parameter and thermal conductivity from the steady state temperature distribution of a point source is also proposed. PMID- 7790739 TI - HSP synthesis of neonatal rat heart myocytes is regulated by a collagen environment. AB - Studies on the stress response of isolated myocytes have gained great importance in the understanding of the response of the heart as an organ after, for instance, ischemia. However, the possible role of the extracellular matrix on these effects has thereby been neglected. The recently developed model system of neonatal heart cells cultured on a collagen gel, characterized by a high coherence of contractions, has been used to study the effects of this more in vivo-like collagen environment on the heat shock response of the myocytes as compared to 'normally used' monolayer cultures. After four days differences were found in the heat-induced synthesis of HSPs of cells grown by the two culturing procedures. The degree of induction of different HSPs appeared to be directly related to the basic level of synthesis of these HSPs under the used culturing conditions. In collagen gel-grown cultures the basic level of synthesis as well as the heat-induced synthesis of HSP84 and HSP100 was decreased, for HSP60 both were increased, and for HSP70 no differences were found compared to the monolayer cultures. Our results suggests that the collagen matrix has a regulatory role in the synthesis of HSPs. PMID- 7790741 TI - A new applicator utilizing distributed electrodes for hyperthermia: a theoretical approach. AB - We propose a new type of applicator for hyperthermia namely a Distributed Electrodes Applicator. Many electrodes are fixed on boli below which the patient is placed. A set of RF with optimized amplitudes and phases is supplied to the electrodes so as to minimize the ratio of SAR (specific absorption rate) in the fat layers to that in the central region of the patient. SAR patterns in a heated material were calculated using two-dimensional finite element method, and the results showed that the proposed applicator can heat the deep portions of the patient without excessive heating of the fat layers. PMID- 7790744 TI - Magnetic resonance angiography and carotid artery stenosis: state of the art. PMID- 7790742 TI - Noninvasive prediction of SAR distributions with an electro-optical E field sensor. AB - An integrated electro-optical (eo) E field sensor is developed on the basis of a Ti:LiNbO3 Mach-Zehnder interferometer. A measuring device based on the lock-in principle is introduced to register the E field in phase and amplitude using this E field probe. Segmented electrodes are used to minimize influences from the dielectric surroundings on the base point capacitance of the receiving dipole. The operating point is stabilized against drift phenomena resulting from optical damage and pyroelectric effect. Sensitivity, dynamic range, harmonic distortions and mechanical properties of a prototype of this electro-optical E field sensor are evaluated. A phantom setup in the SIGMA-60 applicator was developed to test this electro-optical sensor for hyperthermia applications. Power deposition patterns of various standard adjustments of the SIGMA ring are visualized in an elliptical lamp phantom. Simultaneously, E field in phase and amplitude is determined on a closed curve in 10 degrees steps around the phantom in a substitute bolus. The numbers are stored and utilized as boundary conditions in a two-dimensional finite elements code which calculates the SAR distribution on an appropriate triangular grid inside the closed curve. An excellent qualitative agreement is obtained between visualized and calculated SAR patterns. This novel measurement method is therefore suitable for noninvasive monitoring of SAR patterns during clinical application of regional radiofrequency hyperthermia. PMID- 7790743 TI - Oncogenic potential of hyperthermia in combination with radiation. PMID- 7790745 TI - Clinical significance of coronary artery calcification. AB - Coronary artery calcification (CAC) was easily demonstrated by plain CT-scan. The aim of this study was to clarify the clinical significance of CAC in cardiovascular diseases. The subjects were 90 patients with ischemic heart disease (30 myocardial infarction, 50 exertional angina pectoris and 10 variant form of angina pectoris; 46 males and 44 females, 68 +/- 10 y/o) and 50 patients without ischemic heart diseases (30 hypertension, 10 arrhythmia, 3 valvular disease, 2 cardiomyopathy, 2 congenital heart disease and 3 others; 25 males and 25 females 65 +/- 9 y/o). CAC and calcification of thoracic aorta were evaluated by plain CT-scan (1 second scan time and 5 mm slice). The relationship between CAC and other clinical features (age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking, resting ECG, exercise stress ECG, aortic calcification and optic fundi) were studied. CAC were seen more frequently in patients with ischemic heart disease (63%), old age (67%), aortic calcification (70%) and positive exercise testing (64%). On the other hand, CAC were rare in variant angina (30%). In younger patients (under 70 y/o), CAC were seen more frequently in diabetic patients. But, in older patients, CAC were frequently in those with hyperlipidemia. These results suggested that CAC was associated with not only systemic arteriosclerosis, but also ischemic heart disease, except vasospastic angina. The prognostic value of CAC would be studied later. PMID- 7790746 TI - Doppler ultrasonography in giant cell arteritis. AB - A patient with biopsy negative giant cell arteritis was examined and treated by our group. Since in some cases the visual loss in this disease is due to a central retinal artery occlusion, a technique to evaluate the blood flow velocity in this artery would be useful. The Duplex scanner was utilized by us in this patient to study the blood flow velocity of the central retinal artery. The flow velocity was reduced. The patient was treated with systemic steroids which lead to clinical and symptomatic improvement. After the treatment with steroids the Duplex scanner was again used to study the flow velocity of the central retinal artery. The blood flow velocity improved. We think that Doppler ultrasonography may be useful in the diagnosis of and in monitoring the treatment of some cases of giant cell arteritis. PMID- 7790747 TI - Surgical treatment of extracranial carotid aneurysms. AB - During the past 23 years, 12 patients with aneurysm of the carotid bifurcation were treated in our department. There were 11 men and one woman between 20 and 68 years (mean age 54.2 years). In as much as 217 patients were operated on for extracranial occlusive carotid disease during the same period, the incidence of these aneurysms in our series has been estimated to be 5%. Eleven patients presented with TIAs ipsilateral to the aneurysm. One patient presented with a painful pulsatile enlarging mass in the neck (ruptured aneurysm) without any neurological complications. Eleven patients underwent surgical repair. Ligation of the common carotid artery was done in one patient, resection of the aneurysm with end-to-end anastomosis was performed in 2 patients, aneurysmorraphy in 4, excision and reconstruction with reversed saphenous vein in one, excision and reconstruction with PTFE graft in one and 2 patients underwent endarterectomy and angioplasty of the carotid bifurcation. One patient with a high internal carotid artery aneurysm (base of the skull) was classified as nonoperable. There were no deaths or strokes postoperatively. Persistent cranial nerve injury was noted in 1 case (8%). Follow-up at 6 months - 10 years (mean 5.5 years) yielded and incidence of post-op TIAs of 8% attributed to intracranial occlusive disease. Surgical correction is the treatment of choice for extracranial carotid aneurysm and can be performed with a very low morbidity and mortality and carries excellent long-term results. PMID- 7790748 TI - Early results of 132 aortic or aorto-iliac arterial reconstructions with the new Stretch ePTFE vascular prosthesis. AB - OBJECTIVE: The purpose of the present study is to document the short term clinical results after implantation of the new Stretch ePTFE (Gore-Tex) arterial prostheses in patients with aortic or aorto-iliac occlusive atherosclerotic disease or aneurysm. STUDY DESIGN: A descriptive, prospective and non-randomized clinical series with clinical follow-up at three and 12 months. SETTING: The study was performed at an Academic Vascular Surgery Unit. PATIENTS: Within 20 months we consecutively implanted 379 prostheses (tubes or bifurcations): 132 Stretch ePTFE (Gore-Tex) and 247 Dacron (Unigraft, Braun-Melsungen) grafts. RESULTS: There was no intraoperative deaths. Nine of 217 patients (= 4%) with occlusive atherosclerotic disease died < 30 days postoperatively; the mortality rate for asymptomatic aortic aneurysm was 8% (7/91), for symptomatic aneurysm 13% (4/30), and for ruptured aneurysm 22% (8/36). The primary patency of the aortic or aorto-iliac grafts was 99%, secondary patency at three months and one year 100 per cent. One patient with Stretch prosthesis developed a superficial groin infection, and one developed infection of an aortic tube graft. In the Dacron series six patients developed superficial groin infection, and two deep infections occurred. No graft-enteric fistulas or erosions were seen, and by clinical examination no anastomotic aneurysm developed. Five patients had in situ replacement of a pan-infected Dacron bifurcation graft with a Gore-Tex Stretch graft. With an observation time from 50 to 400 days these five patients are well without clinical signs of infection. CONCLUSIONS: These short term results with implantation of aortic or aorto-iliac Stretch ePTFE prostheses are encouraging and will provide the basis for a continuing performance trial with long term follow-up and reporting. PMID- 7790749 TI - Long-term of patients receiving an aorto-bi-femoral prosthesis for atherosclerotic occlusive disease of the aortic bifurcation. AB - Over a 14-year period (1975-1989), 547 patients with a mean age of 57 years received an aorto-bi-femoral prosthesis for atherosclerotic occlusive disease (AOD) and underwent regular follow-up over a 13-year period. Immediate post operative mortality was 2.5% with few deaths due to cardiovascular causes (0.5%). The long-term mortality was significantly elevated at 5 years (10% higher than controls) and at 10 years (16%). These deaths were due to the AOD and its surgical treatment (10%), other cardiovascular disease (30%) and cancer (41%). Approximately 5% of patients required an immediate post-operative, or delayed amputation, compared to 33% which had a threatened limb before the operation. Thrombosis of the prosthesis was relatively rare. At 5 years, 81% of the survivors remained largely improved; at 10 years, 67% and at 13 years, 62%. The benefit of this intervention is therefore unquestionable with regards to the functional state and survival. Also, in avoiding immobility due to the disabling intermittent claudication or amputation, it considerably improves the quality of life which largely compensates for the low mortality rates and subsequent complications of the prosthesis. PMID- 7790750 TI - Morphological changes of dermal blood and lymphatic vessels in chronic venous insufficiency of the leg. AB - Morphological changes of dermal blood and lymphatic microcirculation in skin biopsies from patients affected by Chronic Venous Insufficiency (CVI) associated with stasis dermatitis of the lower limbs, are reported here. Blood vessels are characterized by an occluded lumen, thickening and reduplication of the basement membrane. The structural changes in dermal lymphatic vessels are: (i) collapsed lumen of lymphatics located in the papillar dermis; (ii) numerous and complex interdigitations between contiguous endothelial cells and lack of open junctions; (iii) derangement of the anchoring filaments that normally pull the lymphatic lumen open. The connective matrix is characterized by fibrosis with formation of dense bundles of collagen and elastic fibers. These results suggest that the dermal lymphatic and blood microcirculation in CVI are connected to a reduced fluid exchange capacity because of the structural changes occurred in the vascular and lymphatic wall and in the surrounding connective tissue. PMID- 7790751 TI - Leucocyte activity in chronic venous insufficiency. AB - Before and after venous stasis and upon recovery blood samples were drawn from the saphenous vein in 10 patients with varicose veins (Group 1), in 10 with venous hypertension (Group 2) and in 10 healthy controls. The total leucocyte count, the leucocyte filterability rate (LFR), superoxide dismutase blood concentrations (SOD) and the production of superoxide anions from granulocytes were determined. After stasis, the total leucocyte count increased significantly (p < 0.01) in both groups of patients and the LFR was significantly (p < 0.01) impaired. SOD blood concentrations fell significantly (p < 0.01) and oxygen free radical production dropped significantly (p < 0.01) in both groups. Upon recovery, all parameters returned to normal in Group 1 but significant differences remained in Group 2. No significant modification was observed at any stage of the study in the control group. These results suggest that impairments in leucocyte rheology and granulocyte production of oxygen free radicals cause capillary plugging and possibly damage to microcirculatory vessel walls in venous disease. PMID- 7790752 TI - Effects of hypertension on intimal-medial thickness, left ventricular mass and aortic distensibility. AB - The aim of the study was to evaluate arterial distensibility, intimal-medial thickening of the common carotid artery, left ventricular mass and the eventual correlations among these parameters in the hypertensive state. Our study population consisted of 89 hypertensive patients aged 35 to 80 years (mean age 60.8 +/- 10.6 years), and 76 normotensive subjects aged 45 to 85 years (mean age 61.2 +/- 11.1 years). Those patients constantly presenting systolic blood pressure values > or = 160 mmHg or diastolic blood pressure > 90 mmHg were diagnosed as hypertensive. Each patient underwent a B-mode echotomographic examination of the extracranial carotid tract performed with a Vingmed CFM 750 echotomographer with a 7.5 MHz probe and M-mode echocardiography with a Vingmed CFM 750 device equipped with a 3.0 MHz transducer. The results show the intimal media thickness value in hypertensive patients (0.90 +/- 0.22 mm on the right and 0.92 +/- 0.22 mm on the left), was significantly greater than that in normotensive subjects (0.64 +/- 0.13 mm on the right and 0.64 +/- 0.13 mm on the left, p < 0.001); in hypertensive subjects, interventricular septum thickness (12.1 +/- 1.25 mm) was significantly greater than that in normotensive patients (9.1 +/- 0.77 mm, p < 0.001). In conclusion, we can say that hypertensive subjects have higher values of common carotid artery intimal-medial thickness than normotensives and that this finding is associated with the presence of left ventricular hypertrophy and with a reduction in arterial compliance. Vascular ultrasonography, as well as echocardiography and arterial mechanography can show, in hypertensive subjects, cardiac and vascular abnormalities in a non invasive way. PMID- 7790753 TI - The clinical significance of carotid plaque haemorrhage. AB - The clinical picture with the pathology findings of 89 atheromatic plaques which were removed following endarterectomy of the internal carotid artery, for the purpose of determining the clinical significance of the haemorrhagic atheromatic plaque were correlated. Intraplaque haemorrhage was determined in 44 of the 57 plaques (72.2%) of symptomatic patients while in the asymptomatic patients haemorrhage was noted in 12 of the 32 plaques (37.5%) p < 0.001. The extent of haemorrhage was > 25% of the plaque thickness in 21 of 44 symptomatic plaques (47.72%) and in the asymptomatic plaques in 3 out of 12 (25%) p > 0.05. The incidence of ulceration of the intima, with or without the presence of thrombus, was more frequent in the haemorrhagic plaques (68.42%) as compared with the non haemorrhagic (31.57%), without any significant difference between the symptomatic and asymptomatic plaques. Communication of haemorrhage with the lumen was observed in 8 of 24 plaques (33.33%), 7 of which (29.16%) were symptomatic. The presence of haemorrhage in the atheromatic plaque of the internal carotid artery does not seem to play any direct role in the pathogenesis of the symptoms but, nevertheless, it constitutes a significant indication of instability of the atheromatic plaque. PMID- 7790754 TI - Reconstructive vascular surgery in rotationplasty for malignant tumors of the femur. AB - The rotationplasty procedure of the femur, as first described by Borrgreve, is the functional improvement of an abnormally shortened lower limb. In the last 15 years this procedure has been used in its original form and as modification for tumors of the femur and proximal tibia. The reconstruction of the femoral vessels as an important part of the operation has not enough been accentuated. Principally two types of reconstructions can be performed: the vessels are dissected in the adductor canal or a segmental resection and reanastomosis are performed. Between January 1990 and April 1993 classical and modified rotationplasties were performed for malignant tumors in 34 patients in our institution. In all cases a segmental femoral vessel resection with end-to-end anastomosis were performed. No intra- and postoperative vascular related complications occurred. The authors emphasize the advantage of this method: reanastomosing resected femoral vessels by experienced vascular surgeons is a save, time-saving method. In addition, the radicality of the operation increases in order to obtain excellent long term results. PMID- 7790755 TI - Intraoperative thrombolytic therapy as a treatment of small vessel thrombosis: an experimental study. AB - OBJECTIVE: This paper studies the effect of three doses of Streptokinase infused intra-operatively into an animal model of small vessel thrombosis. EXPERIMENTAL DESIGN: This is a controlled trial of intraoperative infusion of thrombolytic agent into a thrombosed arterial segment compared to no infusion into the contralateral limb. EXPERIMENTAL SUBJECTS: 19 New Zealand White rabbits were stratified into 3 groups. INTERVENTIONS: Thrombosis was achieved by infusing a mixture of topical thrombin and autologous blood into individual iliac arteries of the New Zealand white rabbit. A randomly selected hind limb had an infusion of one of three doses of streptokinase (A = 2,500u; B = 5,000u; C = 10,000u) in saline over 20 minute period. Preinfusion and post infusion angiography was performed. MEASUREMENTS: Angiograms were ranked by a radiologist blinded to the side of infusion and clotting parameters were assessed. RESULTS: All limbs at all doses of streptokinase infusion (SK) showed significant clot lysis when compared to the non-infused limb(C). The percentage of improved segments is as follows: iliac: SK = 100%, C = 79%; femoral SK = 79%, C = 32%; tibial SK = 52%, C = 5%. Although there was an elevation in clotting time and a reduction in fibrinogen, levels remained within normal limits. CONCLUSIONS: Streptokinase infused directly into thrombus in arteries even in low doses significantly enhances thrombolysis of vessels which are too small to be cleared by mechanical means. No significant systemic complications were encountered. PMID- 7790756 TI - The effect of heparin after microsurgical repair in traumatically damaged arteries. AB - A main consideration of microvascular surgery is the avoidance of thrombosis. This traditionally involves the avoidance of thrombogenic trauma, the establishment of normal blood flow and full vessel diameter, as well as the use of anticoagulants, such as heparin, as an antithrombotic measure. In the present study we assessed the effectiveness of heparin in maintaining patency in the femoral arteries of rats which have undergone a crush injury with damage to the intima and media layers of the wall. To accomplish this, the animals were treated with heparin 150 units or 300 units twice daily following microvascular repair using standard microsurgical techniques. Control animals received no treatment. The results of this study indicate that the number of patencies in experimentally injured femoral arteries did not improve significantly following heparin treatment, although pharmacological doses of heparin (300 units twice daily) were associated with a somewhat lower rate of occlusions. We conclude that heparin appears unable to significantly prevent clotting in vessels which have experienced severe trauma to the intima and media layers. PMID- 7790757 TI - Platelet and endothelial response with trapidil in patients with peripheral obliterative arteriopathy. AB - The activity of trapidil, an antiaggregating agent with PDGF antagonist properties, was investigated in order to verify its possible modulating effect in the endothelial and platelet activation. PDGF, t-PA, PAI-1 and ET-1 plasma levels were measured before and after a 2 month treatment period with trapidil 200 mg tablets bid or placebo in 30 patients affected by POA in Fontaine stage II. PDGF and PAI-1 significantly (p < 0.05) increased in the placebo group, and PDGF also in the comparison between treatments (p < 0.05). Aggregation data demonstrate an absence of Ca++ antagonist action of trapidil. The results of this study suggest that trapidil can interfere with the combined vascular and platelet response in atherogenesis. PMID- 7790758 TI - Obstructive uropathy, following redo aortobifemoral by-pass surgery. AB - A rare case of obstruction of the right ureter due to encagement between the right iliofemoral and right limb of an aorto-bilateral femoral Dacron graft is described. Patient was managed successfully by ureterolysis, removal of the occluded right iliofemoral graft, omentoplasty and placement of a pig tail catheter along the right ureter. PMID- 7790759 TI - Fibromuscular dysplasia. A case report with multivessel vascular involvement. AB - A case of multivessel fibromuscular dysplasia involving the cervico-cephalic arteries, the right renal artery and the iliac arteries is reported. It was associated with reversible bilateral internal carotid arteries and vertebral arteries dissection, left thalamic infarct, right hemorrhagic cerebellar infarct, renovascular hypertension and intermittent claudication of the right lower limb. This report indicates that fibromuscular dysplasia is a systemic angiopathy. Renovascular hypertension may foster the appearance of complication such as dissection of the arteries affected by fibromuscular dysplasia. In the case investigated the dissection of cervico-cephalic arteries was followed by spontaneous healing and a favourable neurological outcome whereas at the iliac arteries a rapid deterioration was observed. PMID- 7790760 TI - CAP37, a neutrophil-derived multifunctional inflammatory mediator. AB - Cationic antimicrobial protein of M(r) 37 kDa (CAP37) is a multifunctional protein isolated from the granules of human neutrophils, which has important implications in host defense and inflammation. CAP37 was initially recognized for its strong antibiotic activity against Gram-negative bacteria and was viewed as a component of the oxygen-independent killing mechanism of the neutrophil. However, we now know that CAP37 has more far reaching and important functions. It is a physiological protein released during inflammation with a high potential of regulating monocyte/macrophage functions, such as chemotaxis, increased survival, and differentiation. Recently, it has been demonstrated that CAP37 binds endotoxin. It has the structure of a serine esterase but lacks enzymatic activity. The bactericidal and endotoxin binding domains of the molecule have been delineated. The identification of functional peptides should provide new insight into the mechanisms of endotoxin binding, antimicrobial activity, and chemotaxis and in the long term provide key insights into therapies for treating infections and endotoxic shock. PMID- 7790761 TI - Interleukin-5 and its receptor: a drug target for eosinophilia associated with chronic allergic disease. AB - A characteristic feature of chronic allergic diseases such as asthma is the increase in eosinophil numbers in the inflamed tissue. In light of its specificity for the development of eosinophils, interleukin-5 (IL-5) is considered the most important cytokine involved in the regulation of eosinophilia. Hence, an antagonist for IL-5 activity is a new target for drug discovery programs. We have examined the opportunity for both a random and a rational approach for the identification of such an antagonist. The elucidation of the structure of IL-5 and the initial structure/function analysis of the ligand/receptor complex constitute a first step towards the design of antagonistic compounds. The identification of a small compound by random screening able to inhibit the IL-5/IL-5 receptor interaction indicated an important domain in the receptor. We examine here protein-based IL-5 antagonists, such as IL-5-muteins, soluble IL-5 receptor constructs, and monoclonal antibodies, for their potential as IL-5/IL-5 receptor antagonists, and the use of a murine model of eosinophil airway inflammation for their evaluation. PMID- 7790762 TI - Endotoxin infusion in anesthetized sheep is associated with intrapulmonary sequestration of leukocytes that immunohistochemically express tumor necrosis factor-alpha. AB - Plasma levels of tumor necrosis factor-alpha (TNF-alpha) peak between 2 and 4 h during a 12-h continuous infusion of endotoxin in awake sheep. We hypothesized that a source of this TNF-alpha is the pool of leukocytes that accumulate in the pulmonary circulation. To test this hypothesis, we physiologically monitored six anesthetized sheep during baseline and 4-h endotoxin infusion periods (10 ng/kg x min). We obtained open-lung biopsies at baseline and at 20 min and 2 and 4 h during the endotoxin infusion period for immunohistochemical localization of TNF alpha. The plasma concentration of TNF-alpha increased from an average baseline concentration of 0.06 +/- 0.03 ng/ml (mean +/- SD) to a peak of 1.40 +/- 0.28 ng/ml at 2 h of the endotoxin infusion. We observed increased cytoplasmic TNF alpha immunoreactivity in situ among neutrophils and intravascular mononuclear phagocytes during the endotoxin infusion compared with baseline. Also, the number of immunopositive leukocytes increased in the pulmonary circulation during the continuous infusion of endotoxin. We conclude that TNF-alpha-producing leukocytes accumulate in the pulmonary circulation during endotoxemia. These cells probably contribute to both the rise in the circulating levels of TNF-alpha and the development of acute lung injury. PMID- 7790763 TI - Neutrophils are essential for resolution of primary and secondary infection with Listeria monocytogenes. AB - The role for neutrophils in the resolution of primary and secondary infection with Listeria monocytogenes was studied. The results show that although control mice started to clear Listeria from their spleens and livers between days 2 and 4 of sublethal primary infection and eradicated bacteria in 2 weeks, mice given a specific granulocyte-depleting antibody (RB6-8C5) on days 4 or 6 of infection developed lethal listeriosis. Likewise, treatment of immunized mice with RB6-8C5 monoclonal antibody abolished their acquired ability to resolve a lethal challenge infection. The results demonstrate that neutrophils are necessary for the resolution of secondary and primary Listeria infection. PMID- 7790764 TI - Regulatory effect of aminopeptidase inhibitor (bestatin) on the cervix during induction of ripening by interleukin-8. AB - Bestatin is an immunomodulatory peptide that stimulates the humoral and cell mediated immune system. It also has an inhibitory effect on multiple aminopeptidases. Recently we found that aminopeptidase N inactivates interleukin 8 in vitro. Bestatin successfully suppresses the effect of aminopeptidase N on interleukin-8. During cervical maturation many biochemical changes occur including decrease in collagen concentration and increase in collagenase and elastase activities. Interleukin-8, which has a potent neutrophil chemotactic effect, was found to induce cervical ripening in rabbits. The combination of interleukin-8 with bestatin also induced cervical ripening by providing approximately regular levels of neutrophil numbers, collagenase, and elastase activities. We therefore suggest that this regulatory mechanism also takes place in vivo through the inhibitory effect of bestatin on aminopeptidase N. PMID- 7790766 TI - Relationship of phospholipase C- and phospholipase D-mediated phospholipid remodeling pathways to respiratory burst activation in human neutrophils stimulated by Candida albicans hyphae. AB - Neutrophil (PMN) oxidant release, a key component of defenses against disseminated candidiasis, was preceded by oxidant generation after stimulation by Candida albicans hyphae. Opsonized or unopsonized hyphae triggered phospholipase D (PLD) activation within 5 or 30 s, respectively, forming 1-O-alkyl-phosphatidic acid (alkyl-PA) or 1-O-alkyl-phosphatidyl-ethanol in the presence of ethanol. Ethanol, which competitively lowers phosphatidic acid (PA) production, caused dose-dependent inhibition of superoxide (O2-) generation after hyphal stimulation but altered neither baseline-unstimulated O2- production nor responses to phorbol myristate acetate. PA rises evoked by unopsonized hyphae began 2 min before significant O2- release, also preceding both phospholipase C activation and cytosolic Ca2+ rises. Diacylglycerol (DAG) rose in two distinct phases after stimulation by opsonized or unopsonized hyphae, peaking briefly after 60 or 120 s, respectively, followed by prolonged secondary rises. Initial DAG rises preceded inositol triphosphate elevations evoked by unopsonized hyphae. Though PA rose before DAG, no dephosphorylation of PA to form 1-O-alkyl-DAG was noted. Propranalol, which increases PA accumulation by inhibiting PA phosphohydrolase, lowered PMN O2- responses to hyphae. Early DAG rises temporally overlapped respiratory burst initiation but PMN responses to hyphae were unchanged by a DAG kinase inhibitor, R59022, which blocks phosphorylation of DAG to PA and enhances DAG accumulation. Thus, neither PA nor DAG accumulation individually accounted for triggering PMN O2- responses to hyphae. PLD activation and PA production may facilitate PMN fungicidal responses to hyphae but play an indirect role in initiating the respiratory burst. PMID- 7790765 TI - Slow Ca2+ waves in large myeloid cells as a result of a diffusible cytosolic factor. AB - In the work reported here evidence is provided that shows the slow wave of Ca2+ large neonatal myeloid cells provoked by formyl-Met-Leu-Phe was generated by spatially delayed Ca2+ influx. Evidence is provided that the delay in Ca2+ influx was the result of diffusion of a factor from the Ca2+ storage site, which is responsible for Ca2+ channel opening. The location of the Ca2+ release site was correlated with a region near the nucleus, probably a specialized region of endoplasmic reticulum. It is proposed that similar mechanisms of Ca2+ signaling occur in mature myeloid cells, such as neutrophils, but on a shorter time scale as a consequence of their smaller size. PMID- 7790767 TI - Human eosinophils in culture undergo a striking and rapid shrinkage during apoptosis. Role of K+ channels. AB - In the absence of appropriate stimulus, eosinophils in vitro rapidly exhibit the features of apoptotic cells (nuclear pycnosis, cell shrinkage, DNA fragmentation). By using electronic cell sizing, we precisely measured the volume distribution of human eosinophils during apoptosis. We observed that apoptosis of eosinophils was accompanied by a marked cell volume decrease (approximately 60%). Moreover, analysis of the volume distribution in different experimental conditions (kinetics of apoptosis, inhibition of apoptosis by cytokines) revealed that the cell shrinkage, once triggered, was a fast process in which the intermediate states between normal and shrunken volume had a short half-life. As a model of apoptosis, the eosinophil model allowed us to test the hypothesis that apoptotic cell shrinkage was linked to osmotic changes due to leakage of internal ions. Indeed, in the presence of K+ channel blockers, the shrinkage was inhibited in a dose-dependent manner. In conclusion, our results suggest that eosinophil shrinkage during apoptosis is a striking and rapid phenomenon and osmotic changes due to K+ efflux could be responsible, at least in part, of the volume decrease. PMID- 7790768 TI - Profile of immunoglobulin heavy chain variable gene repertoires and highly selective detection of malignant clonotypes in acute lymphoblastic leukemia. AB - The predominant B cell immunoglobulin heavy chain variable gene (IgH-V) usage and the uniquely rearranged, clonotype-specific variable-diversity-joining region gene (VDJ) sequences were identified in patients with B cell acute lymphoblastic leukemia (B-ALL) using a novel DNA-based gene amplification strategy. The approach allows a thorough and sensitive determination of the number of clonal leukemic IgH rearrangements and their precise V gene usage. This strategy may be applied in the detection of minimal residual disease, in surveillance after induction of disease-free states, and in analyzing the effectiveness of purging autologous bone marrow of malignant clones. An initial primary polymerase chain reaction (PCR), directed by an IgH-J generic primer and a complement of family specific IgH-V primers, defined the major B cell IgH-V gene usage. Use of an IgH J generic primer supplanted the use of a constant region primer anchor and thus eliminated the need to target mRNA by the traditional RNA reverse transcription PCR amplification method. Monoclonality of rearranged VDJ bands was further substantiated by high-resolution denaturant gel electrophoretic analysis. The predominant amplified bands were subcloned and sequenced. By sequencing through VDJ juxtaposed regions, that is, the third complementarity-determining region, clonotype-specific primers were developed and used in a secondary clonotype primer-directed PCR (CPD-PCR) to detect, with extreme sensitivity and specificity, a unique B cell clone. Analysis of the products of the CPD-PCR permitted the detection of a single malignant cell among 1 million polyclonal cells and superseded the constraints of prior studies that have provided a limited evaluation of family variable gene repertoire usage. Leukemic clonal rearrangements were detected in 100% of the eight cases of pediatric and two cases of adult B-ALL studied. Two or more clonal IgH-VDJ amplified sequences were observed in 50% of the B-ALL bone marrows analyzed. In two cases, clonotype specific oligodeoxynucleotide primers, derived from B-ALL VDJ sequences, directed the secondary CPD-PCR, and disease activity was monitored after chemotherapy and allogeneic bone marrow transplantation. PMID- 7790769 TI - Lipopolysaccharide-inactivating activity of neutrophils is due to lactoferrin. AB - Neutrophils can inactivate lipopolysaccharide (LPS), thereby blocking the ability of LPS to prime fresh neutrophils for enhanced fMLP-triggered release of superoxide. Here we show that inactivation of LPS by neutrophils was primarily due to lactoferrin. A time course for inactivating LPS showed that neutrophils (5 million/ml) took 30 min to inactivate 10 ng/ml LPS. Mononuclear cells could not inactivate LPS under the same conditions. Experiments with radioactive LPS showed that inactivated LPS remained in the medium and was not taken up or destroyed by the neutrophils during inactivation. Inactivated LPS still gelled Limulus lysate and primed monocytes. Cell-free medium from neutrophil suspensions also inactivated LPS. A single LPS-inactivating factor was purified from medium by heparin-agarose chromatography. SDS-PAGE showed a single band at 80 kDa, which was identified as lactoferrin by immunoblotting. Antilactoferrin immunoglobulin G removed the LPS-inactivating activity from purified lactoferrin and cell-free medium. Surprisingly, even purified neutrophil lactoferrin required 30 min to inactivate LPS, indicating inherently slow binding of lactoferrin to LPS. PMID- 7790770 TI - Dual function of human IgA antibodies: inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells. AB - We have sought to elucidate the responses of human peripheral blood neutrophils to antigenic surfaces complexed with human specific IgA antibodies obtained either as myeloma proteins that recognize staphylococcal alpha-toxin, or from the serum of patients with subacute bacterial endocarditis due to Streptococcus mutans, or from colostrum. In contrast to IgG, IgA antibodies bound to antigen coated fluorescent microspheres, and subsequently exposed to complement (or not), did not promote phagocytosis, as measured by flow cytometric enumeration of cell associated microspheres. Instead, IgA antibodies interfered with complement dependent phagocytosis mediated by IgG antibodies. These properties were shown by different forms of IgA antibodies, including serum and secretory IgA, as well as by monoclonal or polyclonal antibodies. Neutrophils did not respond to the production of superoxide to IgA antibodies complexed with antigen-coated microspheres or with antigen deposited on a solid surface and IgA antibodies suppressed IgG antibody- and complement-mediated superoxide release. However, neutrophils pretreated with interleukin-8 ingested IgA-opsonized microspheres and released superoxide when exposed to IgA antibody-antigen complexes. IgG antibody antigen complexes did not stimulate increased superoxide release in interleukin-8 treated neutrophils. These findings were consistent with a selective increase in the surface expression of Fc alpha R by interleukin-8-treated neutrophils. We conclude that IgA antibodies interfere with the phagocytic activities of normal circulating human neutrophils and may promote these activities in inflammatory neutrophils activated by interleukin-8 in which Fc alpha R is up-regulated. PMID- 7790771 TI - Ultraviolet radiation reduces phagocytosis and intracellular killing of mycobacteria and inhibits nitric oxide production by macrophages in mice. AB - Exposure of mice to a single or multiple low doses of ultraviolet radiation (UVR) decreases the induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium bovis BCG and Mycobacterium lepraemurium (MLM) and impairs the clearance of bacteria from the lymphoid organs. This study is an attempt to address the mechanism by which UV radiation impairs the clearance of bacteria from the lymphoid organs by determining whether alterations in macrophage function such as ingestion and intracellular killing of mycobacteria or production of reactive nitrogen intermediates might be responsible for these effects. BALB/c or C3H/HeN mice were exposed to a single dose of UVB (280-320 nm) radiation ranging from 0.35 to 45 kJ/m2, and at regular intervals after irradiation, the peritoneal and splenic macrophages were collected, cultured, and infected with live BCG or MLM. Phagocytosis was assessed at 6 h by counting the number of acid-fast bacteria per macrophage after Ziehl-Neelsen staining. The rate of intracellular killing was assessed by lysing the macrophages at 6, 12, 24, and 48 h after BCG infection, plating the suspension on 7H11 agar, and counting the number of colony-forming units 21 days later. Similarly, the nitric oxide production, as measured by nitrite, by macrophages obtained from UVB irradiated and nonirradiated mice in response to BCG was assessed. There was a significant reduction in the uptake of organisms by both peritoneal and splenic macrophages collected from UV-irradiated mice. The intracellular killing of organisms was also significantly reduced, as was the production of nitric oxide by peritoneal macrophages infected with BCG in vitro. These results indicate that UVR affects macrophage functions and are consistent with our hypothesis that impaired clearance of bacteria in vivo results from an alteration in macrophage function. PMID- 7790773 TI - Characterization of a non-granule associated pore-forming protein in agranular lymphocytes. AB - Recently, two populations of small lymphocytes (SL) have exhibited non-major histocompatibility complex (MHC) restricted lysis. Recent studies by numerous laboratories have demonstrated that resting T cells triggered through CD3 and CD28 costimulations can result in immediate, non-MHC restricted killing. Our recent studies with CD3-, CD56+ SL demonstrated that although these cells contained no cytoplasmic granules detected with electron microscopy, they mediated potent NK and ADCC activity. In the present study, we have used a Western blotting technique that allows for the detection and quantitation of total cellular levels of pore-forming protein (PFP). We have found that freshly isolated peripheral non-granulated lymphocytes (both CD3+ and CD3-) contain PFP. In addition, CD3-, CD56+ SL contain levels of PFP similar to those of the highly granular CD3- LGL. In search of non-granule PFP, we exploited the rat NK (RNK) cell lines as a source of other potential cytotoxic factors. A membrane associated PFP, based on Western blotting, was isolated from rat RNK cells. Unlike PFP isolated from granules, this PFP was active after culture in Ca(2+) containing medium. However, the lytic activity isolated from the non-granule PFP of RNK cells was inhibited by monoclonal antibodies to PFP. Collectively, these studies indicate that PFP is present in small agranular lymphocytes (both NK and T cells) and that it is not stored in large cytoplasmic granules. The implication of our results for the acquisition and activation of lytic ability in NK and T cells will be discussed. PMID- 7790774 TI - Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide induced production of IFN-gamma and IL-1 beta by human mononuclear cells. AB - Measurement of cytokine secretion in vitro is usually performed in culture medium supplemented with human serum. We compared the secretion of interferon-gamma and interleukin-1 beta as a parameter for lymphocyte and monocyte activation in RPMI 1640 medium supplemented with fetal calf or autologous serum in serum-free medium and protein-free medium. Four different stimulatory mechanisms were tested: phytohemagglutinin, toxic shock syndrome toxin-1 (TSST-1), lipopolysaccharide (LPS), and zinc ions. We found that the optimal stimulatory zinc concentration depended on the total protein content of the medium, whereas the monokine levels were dependent on the concentration of transport proteins such as transferrin. Monokine induction by LPS or TSST-1 were each influenced by the protein and serum composition in a specific manner. Our results show that the differing mechanisms of cytokine induction are influenced by the medium and serum composition in a diverse but specific manner. Serum- or protein-free medium are especially suitable after superantigen challenge when LPS activity needs to be ruled out or after activation by agents with only a weak stimulatory capacity. PMID- 7790772 TI - Processing of complex antigens and simple hapten-like molecules by epidermal Langerhans cells. AB - Langerhans cells (LCs) are antigen-presenting cells of the skin that trap small contact-sensitizing molecules and induce cutaneous hypersensitivity. LCs can present larger molecules but the mechanisms of processing have required investigation. A system combining in vitro culture of antigen with epidermal cells in the presence of inhibitors, followed by fixation and transfer of these antigen/drug-treated epidermal cells to naive mice, was developed to investigate the steps of antigen processing. Langerhans cells undertake similar, but not identical, pathways for the processing of simple and complex molecules. Complex molecules such as trinitrophenyl conjugated to ovalbumin (TNP-OVA) were internalized and modification required a chloroquine-sensitive proteolysis step and a cycloheximide-sensitive protein synthesis step. This modified product was actively recycled to the cell membrane as presentation was inhibited by blocking receptor translocation with either monensin or cytochalasin B. Small contact sensitizers such as trinitrophenyl did not undergo modification but required internalization and presentation was also inhibited by blocking receptor translocation. PMID- 7790775 TI - Induction of macrophage suppressor activity by fibrosarcoma-derived transforming growth factor-beta 1: contrasting effects on resting and activated macrophages. AB - Tumor-derived transforming growth factor-beta 1 (TGF-beta 1) suppresses several immune responses. Because tumor growth induces macrophage (m phi) suppressor activity, we determined whether murine fibrosarcoma-derived TGF-beta 1 contributed to m phi-mediated suppression of autoantigen- and alloantigen stimulated T cell proliferation. The murine fibrosarcoma Meth-KDE cell line constitutively produced TGF-beta 1. Meth-KDE tumor-bearing host (TBH) syngeneic splenic m phi s suppressed autoantigen- and alloantigen-stimulated normal host (NH) CD4+ T cell proliferation. Pretreatment with Meth-KDE supernatants induced NH m phi s to suppress T cell proliferation as much as TBH m phi s. Anti-TGF-beta 1 antibody treatment reversed Meth-KDE-induced NH m phi-mediated suppression. Recombinant TGF-beta 1-induced m phi-mediated suppression was not blocked during inhibition of prostaglandin E2 (PGE2), nitric oxide (NO), or TGF-beta 1 production. However, Meth-KDE-induced m phi-mediated suppression was partly reduced when PGE2 production was inhibited. Pretreatment with tumor cell-derived TGF-beta 1, but not recombinant TGF-beta 1, increased activated m phi PGE2 production. These results show that additional tumor-derived molecules aid in TGF beta 1-enhanced PGE2 production. Also, TGF-beta 1 alone up-regulates m phi synthesis of suppressor molecules that are different from PGE2, NO, and TGF-beta 1. Although TGF-beta 1 has direct suppressor activity on lymphocytes, these results show that release of tumor cell TGF-beta 1 also induces m phi suppressor activity. PMID- 7790776 TI - Interferon-alpha and interferon-gamma down-regulate the production of interleukin 8 and ENA-78 in human monocytes. AB - The two chemotactic cytokines interleukin-8 (IL-8) and epithelial neutrophil activating protein 78 (ENA-78) were recently shown to be potent chemoattractants and activators of neutrophil function and to be present in certain inflammatory diseases. We have studied the effects of recombinant and natural interferon-alpha (IFN-alpha) and of recombinant interferon gamma (rIFN-gamma) on the production of IL-8 and ENA-78 in lipopolysaccharide- and interleukin-1-stimulated human monocytes. Both types of interferons showed a strong, concentration-dependent inhibition of neutrophil-stimulating bioactivity. Similarly, the secretion of IL 8 and ENA-78 was also inhibited by up to 73%. Northern blot experiments demonstrated that IFN-alpha decreases the steady-state levels of IL-8 and ENA-78 mRNA in monocytes, suggesting that IFN-alpha as well as IFN-gamma may control the expression of neutrophil chemotactic cytokines at the mRNA level. PMID- 7790777 TI - Macrophage colony stimulatory factor-activated bone marrow macrophages suppress lymphocytic responses through phagocytosis: a tentative in vitro model of Rosai Dorfman disease. AB - NBXFO hybridoma cells produced macrophage colony-stimulating factor (M-CSF), which stimulated the growth of murine bone marrow-derived macrophages with potent suppressor activity. These macrophages suppressed lymphocyte responses to mitogens and antigens in a dose-dependent manner. Using a transwell chamber, we demonstrated that macrophages needed physical contact with the lymphocytes to suppress lymphocyte proliferation on day 1 in the concanavalin A mitogen reaction. In addition, no soluble suppressor factor was detected at that time. The number of lymphocytes disappeared with time when they were cocultured with the macrophages. Electron microscopy revealed that the macrophage phagocytosized the lymphocytes after 7 1/2 h. Dextran sulfate, heparan, and fucoidan prevented the macrophages from suppressing the lymphocytes. This phenomenon resembles the human disease sinus histiocytosis, also called Rosai-Dorfman disease, in which macrophages (histiocytes) phagocytosize autologous lymphocytes; occasionally, this disease is associated with immunological abnormalities. Thus we believed that macrophage-activating cytokines, such as M-CSF, may stimulate macrophages to phagocytose lymphocytes in vivo. PMID- 7790780 TI - Role of YopH in the suppression of tyrosine phosphorylation and respiratory burst activity in murine macrophages infected with Yersinia enterocolitica. AB - Tyrosine phosphorylation is an important component of the signaling pathways responsible for the activation of the macrophage respiratory burst. Because the virulence plasmid of Yersinia enterocolitica encodes a phosphotyrosine phosphatase, YopH, it is possible that the pathogenic strategy of Y. enterocolitica involves the disruption of tyrosine phosphorylation in the macrophage leading to inhibition of respiratory burst activity. We have investigated the effects of Yersinia infection on tyrosine phosphorylation and respiratory burst activity in murine bone marrow-derived macrophages. Infection of macrophages with virulent [Ye(pYV+)] but not avirulent [Ye(pYV-)] strains of Y. enterocolitica was found to suppress both tyrosine phosphorylation and respiratory burst activity in response to zymosan. Mutational inactivation of YopH reversed the suppressive effect of Ye(pYV+) on zymosan-induced tyrosine phosphorylation, indicating that YopH is responsible for the dephosphorylation of macrophage phosphotyrosine-containing proteins observed in macrophages infected with the virulent strain of Y. enterocolitica. In contrast, mutational loss of YopH failed to reverse the inhibitory effect of Ye(pYV+) on the zymosan-triggered respiratory burst. We conclude that the inhibition of the macrophage respiratory burst by Y. enterocolitica involves a plasmid-encoded virulence protein(s) other than, or in addition to, YopH. PMID- 7790778 TI - Elevation of rainbow trout Oncorhynchus mykiss macrophage respiratory burst activity with macrophage-derived supernatants. AB - A variety of supernatants were prepared by stimulating rainbow trout Oncorhynchus mykiss head kidney macrophages with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), or a leucocyte-derived macrophage-activating factor (I MAF), individually and in combination. If generated using a 12-h stimulation period, such supernatants were found to elevate significantly the respiratory burst activity of target macrophages; that is, they contained a macrophage derived MAF (m-MAF), but supernatants generated using a shorter incubation period showed no significant activity. Combinations of these treatments were particularly effective in generating m-MAF-containing supernatants. The elevation of respiratory burst activity by supernatants generated using combined treatments could be partially inhibited by prior treatment of the target macrophages with anti-TNF-alpha receptor 1 (TNFR1) monoclonal antibodies (mAbs). Similarly, treatment of macrophages with combinations of 1-MAF and m-MAF generated supernatants with potent m-MAF activity and this activity was partially inhibited by prior treatment of the target cells with anti-TNFR1 mAb. In addition, the presence of anti-transforming growth factor beta 1 (TGF-beta 1) serum while generating these latter supernatants resulted in significantly increased m-MAF activity. Such data suggest that fish leukocytes secrete a variety of potent macrophage-activating (TNF-alpha) and -deactivating (TGF-beta) factors. PMID- 7790779 TI - CD82, tetra-span-transmembrane protein, is a regulated transducing molecule on U937 monocytic cell line. AB - The mononuclear cell surface protein IA4, recently classified as CD82, was originally identified in our laboratory by the IA4 monoclonal antibody (mAb), because of its high expression on three lymphoblastoid, LAK-susceptible, variant cell lines. We have characterized CD82 as a new activation/differentiation marker of mononuclear cells. This protein belongs to the new family of TST proteins (tetra spans transmembrane), which includes CD9, CD37, CD53, CD63, and CD81 (TAPA 1). Here we demonstrate that cross-linking of IA4 mAbs induces an increase of intracellular free calcium in U937 cells and tyrosine phosphorylation of various proteins. Our data indicate that the intracellular calcium increase is initiated by a phospholipase C (PLC)-induced PtdIns(1,4,5)P3 second messenger followed by a more stable change, linked to extracellular calcium entry. This transducing signal was dependent on dual engagement of both CD82 and Fc receptors. Surface cross-linking of CD82 together with Fc receptors (FcRs) induces a specific long lasting increase of intracellular calcium, whereas FcR cross-linking alone induces only a transient calcium mobilization. These results suggest that, upon cross-linking of CD82, a multimolecular complex including CD82 and FcR could be induced that is able to trigger signal transduction. We have previously shown that CD82 membrane expression is up-regulated during differentiation of human monocytes. Using U937 cells, we demonstrate here that several cytokines [interleukin-1 beta (IL-1 beta), IL-4, IL-6, IL-13, interferon-gamma, tumor necrosis factor alpha] could significantly up-regulate the surface expression of CD82 antigen, by contrast with FcR surface expression, which was up-regulated only after IFN-gamma treatments. Based on our finding of a strict dependence of CD82 activation on FcR stimulation, we suggest a putative role of CD82 in enhancing FcR-mediated activation of cells from the monocyte/macrophage lineage. PMID- 7790781 TI - Chiropractic treatment of frozen shoulder syndrome (adhesive capsulitis) utilizing mechanical force, manually assisted short lever adjusting procedures. AB - OBJECTIVE: To describe treatment of frozen shoulder syndrome (adhesive capsulitis) via conservative chiropractic treatment to the shoulder joint, utilizing specific contact, low force, instrumental adjusting procedures. A case report, providing an illustrative example of the same, is presented along with a review of the relevant literature. CLINICAL FEATURES: A 53-yr-old woman suffered severe shoulder pain of over 6 months' duration. The patient had been diagnosed as having adhesive capsulitis and had undergone a variety of different treatment regimens without obtaining relief, including various NSAIDs, analgesics and physical therapy. At the time of her presentation, her condition had progressed to the point of near total immobility of the shoulder joint, accompanied by severe pain with resulting marked restriction in her normal activities of daily living. INTERVENTION AND OUTCOME: The patient's shoulder was conservatively managed with chiropractic adjustments to the affected shoulder joint, as well as to the cervicothoracic spine. Treatment consisted of mechanical force, manually assisted short lever chiropractic adjustments, delivered via an Activator Adjusting Instrument. Successful resolution of the presenting symptomatology was achieved. CONCLUSION: Chiropractic care may be able to provide an effective mode of therapeutic treatment for certain types of these difficult cases. Low force instrumental adjustments, in particular, may present certain benefits in these cases that the more forceful manipulations and/or mobilizations cannot. As such, further formal investigation of this type of therapeutic intervention for treatment of frozen shoulder may be warranted on a larger scale. PMID- 7790782 TI - Chiropractic scope of practice: another perspective. PMID- 7790783 TI - Use of spinal manipulative therapy in the treatment of duodenal ulcer: a pilot study. PMID- 7790784 TI - A survey of 492 U.S. chiropractors on primary care and prevention-related issues. AB - OBJECTIVE: To gain information on the issue of scope of chiropractic practice, particularly in relation to primary care and prevention. DESIGN: A survey was administered by mail to a random sample of 753 U.S. chiropractors. SETTING: The sampling frame was stratified into eight geographic regions with approximately equal numbers of D.C.'s to ensure that all areas of the U.S. were represented. PARTICIPANTS: Chiropractors listed in the National Directory of Chiropractic, 1993-4 edition, comprised the sampling frame. RESULTS: Of the 753 D.C.'s sampled, 492 completed surveys, for a response rate of 65.3%. The majority of respondents (90.4%) considered themselves primary care practitioners. Over 80% were accessible to patients at all times. Only 4.1% accepted payment in cash only. Fifty-eight percent did a regional physical exam, 29.0% a complete physical, and 71% a complete health history on every patient. Referrals to M.D.'s/D.O.'s were made by 78.1% and received by 46.0% within the last 3 months, although fewer than 20% included reports with referrals. Prevention practices related directly to musculoskeletal problems were most often designated as important to discuss with patients: lifting techniques (78.0%), postural education (76.4%), fitness exercise (69.3%) and injury prevention (68.3%). CONCLUSIONS: In general, respondents demonstrated a number of practice characteristics associated with primary care. However, it appears that they could further strengthen their position by routinely accompanying referrals with reports, and by increasing their emphasis on prevention, especially in areas not directly related to musculoskeletal conditions. PMID- 7790787 TI - Low back pain outcome measurement assessment in chiropractic teaching clinics: responsiveness and applicability of two functional disability questionnaires. AB - OBJECTIVE: The major aims were to evaluate responsiveness and clinical/research applicability of the Revised Oswestry Disability Questionnaire (ODQ) and the Dallas Pain Questionnaire (DPQ). Construct and content validity were assessed. Patient characteristics and outcomes were also documented. DESIGN: Longitudinal observational study. SETTING: College outpatient clinics. PARTICIPANTS: Six hundred sixty-three consecutive new patients accepted for treatment of low back pain (LBP) at the clinics over a 1-yr period, age 18 or older. INTERVENTIONS: Treatment of low back pain by senior interns under the supervision of staff clinicians. MAIN OUTCOME MEASURES: ODQ and DPQ administered at baseline, 2 wk, 1 month, and monthly up to 6 months. Responsiveness: mean standardized change score (delta' = mudif/sigma dif), relative efficiency ([RE = delta' ODQ/delta DPQ']2), and improvement rates (IR). Applicability: instrument completion rates. Construct validity: correlation with VAS for pain intensity. RESULTS: ODQ responsiveness was generally consistent over time (delta' = .70-.83) and negligibly better than the DPQ activities of daily living scale (RE = 1.00-1.35); most patients self reporting improvement showed positive outcomes (IR = 97%). For large samples (n > 100): delta' = .47-.63 and IR = 81% for the DPQ work/leisure scale; delta' = .17 .40 and IR = 54% for the DPQ anxiety/depression and social dimensions. Completion rates: 65%-78% of all instruments; 81%-100% of individual scales. Construct validity: r = .44-.68 for the ODQ, DPQ activities of daily living, and DPQ work/leisure scales; r = .20-.40 for the anxiety/depression scale. CONCLUSIONS: The ODQ and the activities of daily living and work/leisure scales from the DPQ appear appropriate for monitoring LBP patients returning for care to chiropractic teaching clinics. The social and anxiety/depression dimensions of the DPQ do not appear to be responsive in this population. The latter scale may be unsuitable on the grounds of misinterpretations. PMID- 7790789 TI - L5 vertebral compression fracture: a series of five cases. AB - OBJECTIVE: The purpose of this paper is to discuss five cases of L5 vertebral compression fracture (VCF), illustrating the epidemiology, clinical presentation and radiographic appearance of the fracture at this uncommon site. Additionally, an empirical approach to conservative management of L5 VCFs is also discussed. DESIGN: A series of five cases. SETTING: Private chiropractic clinic. CONCLUSIONS: Compression fractures at the L5 level are rare; however, this problem should be considered in postmenopausal women who suffer from low back pain and in young men with a history of trauma. Conservative treatment options, including both passive therapy and exercise, can be beneficial in the management of this condition. PMID- 7790785 TI - Analysis of zygapophyseal joint cracking during chiropractic manipulation. AB - OBJECTIVES: To determine if there is a relationship between the side of head rotation and the side of joint crack during "diversified" rotatory manipulation of the cervical spine. DESIGN: Randomized experimental study. SETTING: Macquarie University, Centre for Chiropractic, Summer Hill, New South Wales. SUBJECTS: Fifty asymptomatic subjects were recruited from the students and staff of the above college. INTERVENTION: Single, unilateral "diversified," high velocity, low amplitude, rotatory thrust technique. MAIN OUTCOME MEASURES: Joint crack sound wave analysis of digital audio tape (DAT) recordings, taken from two skin mounted microphones positioned on either side of the cervical spine. RESULTS: All 50 subjects exhibited at least one audible joint crack sound during manipulation. Forty-seven subjects (94%) exhibited cracking on the ipsilateral side to head rotation (95% confidence interval, 83.5% to 98.7%). One subject exhibited joint cracking on the contralateral side only, while two subjects exhibited bilateral joint crack sounds. There was a statistically significant lower rate of exclusively ipsilateral joint cracking in subjects with a history of neck trauma (80% vs. 100%, p = .023). CONCLUSIONS: This research suggests that during the "diversified" rotatory manipulation of the cervical spine utilized in this study, there is a higher occurrence of the joint crack on the ipsilateral side to head rotation. PMID- 7790786 TI - The effect of exercise on the presence of leukocytes, erythrocytes and collagen fibers in skeletal muscle after contusion. AB - OBJECTIVE: To determine the comparative rate of resolution of a contusion resulting from mechanical trauma to skeletal muscle, as a function of one of four exercise regimens. DESIGN: Randomized control trial. The four exercise regimens were: running with its onset immediately after injury, running with a 72 hr delay after injury, swimming with immediate onset, or swimming with a 72 hr delay. Control did not exercise. SETTING: Small-animal laboratory. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTION: A small animal traumatizing machine applied to the biceps femoris. MAIN OUTCOME MEASURES: The rate of contusion resolution was determined by a manual count of erythrocytes, leukocytes and collagen fibers in the contusion, and the data were analyzed using analysis of variance. RESULTS: Exercise of any type produced a greater decline in erythrocyte count (28.2% after 32 days vs. control) than no exercise. Immediate onset of any of the exercise regimens after injury resulted in a greater decline in erythrocyte count (32.7% after 32 days vs. control) and in leukocyte count (17.3% after 32 days vs. control) than delayed onset. Running with either immediate or delayed onset of exercise after injury produced a greater decline in erythrocyte count (36.2% after 32 days vs. control) than swimming. Running with its onset immediately after injury produced the greatest overall rate of decrease in erythrocyte count (44.8% after 32 days vs. control), and the second greatest overall rate of decrease in leukocyte count (15.0% after 32 days vs. control). CONCLUSIONS: Running with immediate onset is the regimen of choice. Any of the given exercises is preferable to no exercise, immediate onset of exercise is preferable to delayed onset, and running is preferable to swimming. PMID- 7790790 TI - Chiropractic manipulation of anteriorly displaced temporomandibular disc with adhesion. AB - OBJECTIVE: This AB, single-subject case study was conducted to investigate the capability of chiropractic manipulation of the temporomandibular joint (TMJ) in treating unilateral anterior displacement of the articular disc with adhesion to the articular eminence. A specific joint manipulation was designed to reduce the anteriorly displaced and adhered TMJ disc. CLINICAL FEATURES: A 21-yr-old woman suffered from a four year history of right-sided temporomandibular joint pain and clicking, with limitation of mandibular opening. The patient reported previous unsuccessful treatments for her condition. An exhaustive history, a complete review of systems and a physical examination (including, but not limited to, eyes, ears, nose, throat and motor, sensory and reflex neurological tests) were obtained. Relevant or contributory findings are extracted for this article. A clinical diagnosis of left-sided anteriorly displaced TMJ disc with adhesion to the articular eminence was made. INTERVENTION AND OUTCOME: Patient's pain level, presence of joint clicking upon mandibular opening and the amount of mandibular opening were used as outcome measures for capability of treatments. An AB, single subject study was used where A was the baseline period and B the therapeutic intervention period. The patient was treated twice a week for a total of 19 visits. During the baseline period no treatment was given to the TMJ (3 visits) where the patient received cervical manipulation alone. During the experimental period the patient received both cervical spine manipulation and a specific manipulation to the left mandible. There were no physical therapeutic modalities applied to the jaw. The specific TMJ manipulation used requires a very low amplitude high velocity thrust parallel to the slope of the articular eminence. The results of this study show mandibular opening distance was returned to normal in addition to the abolition of the patient's TMJ pain and clicking. During the three baseline visits mandibular opening showed no significant change, with an average of 25.3 mm (range 25-26 mm). There was also no change in the patient's TMJ pain or clicking during this baseline period. The patient's TMJ clicking was absent following the third treatment and the patient reported significant subjective pain relief as well. Temporomandibular pain was again reported during the fifth, sixth and seventh post-treatment visits due to exacerbations caused by daily activities. There was no pain reported from the beginning of the eighth post-treatment visit to the end of the study. CONCLUSION: The findings of this study show this specific manipulation of the TMJ may be appropriate for the conservative treatment of adhered anteriorly dislocated disc. PMID- 7790788 TI - Measuring cervical muscle tenderness: a study of reliability. AB - PURPOSE: To study the inter- and intraexaminer reliability of assessing palpatory cervical muscle tenderness using a Total Tenderness Score System. DESIGN: Blinded, repeated measures of cervical muscle Total Tenderness Score. SETTING: Primary contact ambulatory outpatient facility in a publicly (National Health Service) funded chiropractic research institution. PARTICIPANTS: Fourteen asymptomatic volunteers, seven male and seven female, aged 23-45 yr. INTERVENTION: Palpatory assessment of cervical muscle tenderness by two blinded examiners, three times in all per subject. MAIN OUTCOME MEASURES: Total Tenderness Score (TTS), measured on a rank/ordinal scale. RESULTS: The inter- and intraexaminer reliability of TTS was evaluated using a Spearman rank correlation coefficient (r = .88 and r = .85, respectively), and using a Wilcoxon paired rank sum test (p = .85 and p = .07, respectively) and by visual inspection of a scatter-plot. CONCLUSION: The Total Tenderness Score system was deemed to possess acceptable reliability for use in the cervical muscles. PMID- 7790791 TI - Chiropractic in The Netherlands: a survey of Dutch chiropractors. AB - BACKGROUND: In the Netherlands, there is increasing public and political interest in chiropractic treatment. There is, however, very little descriptive information available in the Netherlands on the chiropractic profession. Therefore, a survey was conducted among all Dutch chiropractors. METHODS: A questionnaire was sent to all members of the Netherlands' Chiropractors Association (n = 59). It contained questions on (postgraduate) education, practice management, diagnostics (including radiology use), treatment, interprofessional cooperation and referral. RESULTS: The response was 88%. Chiropractic is growing rapidly: the number of chiropractors has doubled in five years. Chiropractors primarily treat back and neck pain, with an average of 8 treatments. Conventional orthopedic and neurological examination along with motion palpation are the cornerstones of physical examination. The respondents stressed the importance of direct access to radiography and specialized (hospital) diagnostics. Fifty-eight percent of the chiropractors have their own X-ray equipment. The most frequent reason for taking new X-rays was the absence of cooperation with radiology departments. Self referral is the largest source of patients. The referral rate to other health care professionals is low. CONCLUSIONS: The number of chiropractors is growing rapidly. They have an exceptional position in the Dutch health care system. Access to X-ray and more specialized diagnostics are presently the most important political issues. PMID- 7790792 TI - Chiropractors' attitudes toward training in prevention: results of a survey of 492 U.S. chiropractors. AB - OBJECTIVE: To assist in assessing practicing DCs' attitudes toward and expressed needs for prevention-related training, particularly those topics most relevant to a primary care practice. DESIGN: Data were obtained from a mail survey of a random sample of 753 U.S. chiropractors. Data analysis included stratification and multiple logistic regression to examine the effects of gender, years of practice and chiropractic college attended on training, reported in 23 prevention topics. Responses were compared with those from a similar published survey of MDs. SETTING: The sampling frame was stratified into eight geographic regions with approximately equal numbers of DCs. PARTICIPANTS: The sampling frame consisted of chiropractors listed in the 1993-4 edition of the National Directory of Chiropractic. RESULTS: The survey response rate was 65.3%. Although 90.4% of respondents consider themselves primary care practitioners, a significantly fewer (p = .00) 78.5% reported adequate training as such in chiropractic college. Fewer women than men reported adequate training. Respondents with fewer years in practice reported more training in chiropractic college for fourteen of twenty three prevention topics than respondents with more years in practice. Differences in reported training were detected among graduates of different chiropractic colleges in two topics: cancer detection and immunization, con aspect. Comparing this survey to that of MDs, more primary care MDs than DCs reported training in every topic. When training in addition to that in chiropractic college was reported, DCs reported training that more closely approximated primary care MDs. CONCLUSIONS: The self-reported information in this survey may provide some insight into respondents' perception of their education in prevention and their need for additional training. These findings indicate that although prevention training seems to be increasing in the chiropractic colleges, an apparent need exists for further emphasis on preventive care, particularly in areas most relevant to a primary care practice. PMID- 7790793 TI - The efficacy of traction for lumbar back pain: design of a randomized clinical trial. AB - OBJECTIVE: To present the design of a trial on the efficacy of lumbar traction. DESIGN: Randomized clinical trial. PATIENTS: Patients with a minimum of 6 wk, nonspecific low back pain. INTERVENTION: High-dose, motorized, continuous traction with a force between 35% and 50% of the total body weight was compared with sham or low-dose traction with a force between 0 and 20% of body weight. The sham traction was given with a specially developed brace that becomes tighter in the back during traction. This is experienced by patients as if traction were exerted. OUTCOME MEASURES: Primary measures were the patient's global impression of the effect and the severity of three main complaints. Secondary effect measures were functional status, pain, range of motion, work absence and recurrences. The effect measures were rated before randomization and 4 wk, 12 wk and 6 months later. CONCLUSION: There have been a number of earlier trials on the efficacy of lumbar traction; they suffer, however, from severe methodological flaws. This trial aimed to avoid these shortcomings. PMID- 7790795 TI - The audible release associated with joint manipulation. AB - OBJECTIVE: The objective of this paper is to review the literature on the audible release associated with manipulation. DATA SOURCES: Bibliographic information in pertinent articles and papers located in the MEDLINE database containing the keywords joint, joints, cartilage, crack, cracking, cavitation, crepitus and noise. STUDY SELECTION: All articles relevant to the objectives were selected. DATA EXTRACTION: All available data was used. DATA SYNTHESIS: The audible release is caused by a cavitation process whereby a sudden decrease in intracapsular pressure causes dissolved gasses in the synovial fluid to be released into the joint cavity. Once a joint undergoes cavitation, the force-displacement curve changes and the range of motion of the joint increases. The gasses released from the synovial fluid make up about 15% of the joint volume and consist of approximately 80% carbon dioxide. Habitual joint cracking does not correlate with arthritic changes, but does correlate with loss of grip strength and soft-tissue swelling. During the "crack" associated with a joint manipulation, there is a sudden joint distraction that occurs in less time than that required to complete the stretch reflexes of periarticular muscles. Theories on the cavitation mechanism were reviewed and new information on the cavitation process is introduced. In this paper, it is proposed that the cavitation process is generated by an elastic recoil of the synovial capsule as it "snaps back" from the capsule/synovial fluid interface. CONCLUSIONS: Because the sudden joint distraction during a manipulation occurs in a shorter time period than that required to complete the stretch reflexes of the periarticular muscles, there is likely to be a high impulse acting on the ligaments and muscles associated with the joint. This is an important conclusion, because others have proposed that reflex actions from high threshold periarticular receptors are associated with the many beneficial results of manipulation. This suggests that the cavitation process provides a simple means for initiating the reflex actions and that without the cavitation process, it would be difficult to generate the forces in the appropriate tissue without causing muscular damage. PMID- 7790794 TI - Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial. AB - OBJECTIVE: To compare the effectiveness of spinal manipulation and pharmaceutical treatment (amitriptyline) for chronic tension-type headache. DESIGN: Randomized controlled trial using two parallel groups. The study consisted of a 2-wk baseline period, a 6-wk treatment period and a 4-wk posttreatment, follow-up period. SETTING: Chiropractic college outpatient clinic. PATIENTS: One hundred and fifty patients between the ages of 18 and 70 with a diagnosis of tension-type headaches of at least 3 months' duration at a frequency of at least once per wk. INTERVENTIONS: 6 wk of spinal manipulative therapy provided by chiropractors or 6 wk of amitriptyline treatment managed by a medical physician. MAIN OUTCOME MEASURES: Change in patient-reported daily headache intensity, weekly headache frequency, over-the-counter medication usage and functional health status (SF 36). RESULTS: A total of 448 people responded to the recruitment advertisements; 298 were excluded during the screening process. Of the 150 patients who were enrolled in the study, 24 (16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%) from the amitriptyline therapy group. During the treatment period, both groups improved at very similar rates in all primary outcomes. In relation to baseline values at 4 wk after cessation of treatment, the spinal manipulation group showed a reduction of 32% in headache intensity, 42% in headache frequency, 30% in over-the-counter medication usage and an improvement of 16% in functional health status. By comparison, the amitriptyline therapy group showed no improvement or a slight worsening from baseline values in the same four major outcome measures. Controlling for baseline differences, all group differences at 4 wk after cessation of therapy were considered to be clinically important and were statistically significant. Of the patients who finished the study, 46 (82.1%) in the amitriptyline therapy group reported side effects that included drowsiness, dry mouth and weight gain. Three patients (4.3%) in the spinal manipulation group reported neck soreness and stiffness. CONCLUSIONS: The results of this study show that spinal manipulative therapy is an effective treatment for tension headaches. Amitriptyline therapy was slightly more effective in reducing pain at the end of the treatment period but was associated with more side effects. Four weeks after the cessation of treatment, however, the patients who received spinal manipulative therapy experienced a sustained therapeutic benefit in all major outcomes in contrast to the patients that received amitriptyline therapy, who reverted to baseline values. The sustained therapeutic benefit associated with spinal manipulation seemed to result in a decreased need for over-the-counter medication. There is a need to assess the effectiveness of spinal manipulative therapy beyond four weeks and to compare spinal manipulative therapy to an appropriate placebo such as sham manipulation in future clinical trials. PMID- 7790796 TI - Spondyloepiphyseal dysplasia tarda. AB - OBJECTIVE: To present a case of spondyloepiphyseal dysplasia (SED) tarda in a 14 yr-old boy. CLINICAL FEATURES: The patient suffered from chronic bilateral hip pain and range of movement was decreased. Radiographic examination showed findings consistent with skeletal dysplasia tarda. INTERVENTION AND OUTCOME: The patient was given specific stretching exercises and encouragement to stay active. Physiotherapy was provided to strengthen the hip adductor muscles. CONCLUSION: The presence of short stature, symmetrical hip dysplasia and abnormal vertebral bodies should raise the suspicion of a skeletal dysplasia, specifically spondyloepiphyseal dysplasia. PMID- 7790797 TI - Charcot-Marie-Tooth disease. AB - OBJECTIVE: To discuss the similarities and differences in the clinical presentation of Charcot-Marie-Tooth Disease, an inherited peripheral neuropathy, and acquired lumbar spinal stenosis. CLINICAL FEATURES: Patients with lumbar spinal stenosis causing nerve root entrapment often have leg pain and weakness during such activities as walking or standing. Additional symptoms of poor balance, foot deformity and signs of cerebellar and sensory ataxia suggest a diagnosis of peripheral neuropathy rather than nerve root entrapment. INTERVENTION: Electrodiagnostic testing and nerve conduction studies reveal abnormal conduction velocities in cases of peripheral neuropathy such as Charcot Marie-Tooth Disease. CONCLUSION: Sciatica and leg weakness may be due to a variety of causes, including nerve root entrapment and peripheral neuropathy. A diagnosis of Charcot-Marie-Tooth Disease should be considered in a case of progressive lower limb weakness associated with loss of balance and sensory ataxia. This diagnosis can be confirmed using nerve conduction studies. PMID- 7790798 TI - The treatment of presumptive optic nerve ischemia by spinal manipulation. AB - OBJECTIVE: To discuss a case of presumptive optic nerve ischemia successfully treated by spinal manipulative therapy. CLINICAL FEATURES: A 62-yr-old male patient suffered from a 1-wk history of monocular visual defect in association with headaches and neck strain. Ocular examination revealed no pathology in the optic nerve head or retina that could explain the abnormality of vision. Based on physical signs, a presumptive diagnosis of optic nerve ischemia was made. INTERVENTION AND OUTCOME: Vision improved dramatically in the week of spinal manipulation therapy, as measured by serial computerized static perimetry. CONCLUSION: This case study records improvement in optic nerve function when measured before and after spinal manipulation using computerized static perimetry. It contends that spinal manipulation can affect the function of the optic nerve in some patients, presumably by increasing vascular perfusion. I hypothesize that derangement of the cervical spine produces microvascular spasm in the cerebral vasculature, including that of the eye. PMID- 7790799 TI - Where do we go from here? PMID- 7790800 TI - Some anthropometric dimensions of male adolescents with idiopathic low back pain. PMID- 7790801 TI - Chiropractic management of primary nocturnal enuresis. PMID- 7790802 TI - Telemedicine in the 90's: beyond the future. PMID- 7790804 TI - The role of telemedicine in disaster medicine. AB - Telecommunications from telephone and radio to two-way audio, video, facsimile (fax), and digital imaging via satellite transmission have been used in responses to disasters. Current and rapidly emerging communications technology offers the prospect of enormously expanded and more efficient application in predisaster, acute, and postdisaster rehabilitation activities. A survey of present and potential roles for telemedicine in disaster medicine will be presented with particular focus on initial on-going medical needs assessment, prevention programs, and emergency assistance for provision of emergency care of victims, care for other survivors, and public health and sanitation services. Attention will also focus on telemedicine in education and training, disaster response exercises, development of comprehensive plans, and research. Finally, the essential relationship between the routine utilization of telemedicine in predisaster health care and effective employment in disaster situations will be discussed. PMID- 7790803 TI - Current status of domestic telemedicine. AB - This manuscript addresses several aspects of the current status of telemedicine in the United States. Telemedicine programs have been in existence since the 1960s, but only in the last 2 or 3 years have they begun to proliferate. Teleradiology has grown rapidly, both in the number of systems and the volume of images transmitted. Clinical telemedicine consultation, using video-conferencing, has seen an increase in the number of programs, but patient volumes remain low. In this paper, I discuss the scope and effectiveness of telemedicine, the kinds of applications in use at various telemedicine centers, and issues of importance in the development and integration of telemedicine systems into the health care delivery infrastructure. PMID- 7790805 TI - Second NASA/USUHS International Conference on Telemedicine for Remote Health Care and Disaster Response, held September 8-10, 1994, in Bethesda, Maryland. PMID- 7790806 TI - Survey of global telemedicine. AB - The number and scope of telemedicine projects and applications world-wide are growing rapidly along with exponential expansions in national and international information infrastructures and computer capabilities to support them. To track these rapid changes, the Center for Public Service Communications (CPSC) of Arlington, VA, developed the Telemedicine and Information Technologies in Health Care: Project Tracking Document for the National Aeronautics and Space Administration (NASA). This document is maintained by CPSC and frequently updated. It tracks the following areas in telemedicine and health care informatics: (1) major existing Federal grant and other assistance programs and activities; (2) legislation effecting policy in these areas; (3) projects using various technologies throughout the US; and (4) telemedicine projects/interests in other nations. This paper is a survey of international (global) telemedicine activities that are outlined in that document. PMID- 7790808 TI - Opportunities and challenges to telemedicine in rural America. AB - Rural communities have chronically suffered from a lack of adequate health care resources. Too few primary care practitioners and the need to travel long distances for specialty care have made it difficult for many rural residents to receive the care they need when they need it. Telemedicine provides one tool for improving this situation. As is often the case, however, telemedicine's potential has not been realized in rural America. Significant technical, regulatory, organizational, and financial barriers have prevented rural communities from benefiting from the technology. This paper discusses these issues and suggests a prescription for establishing successful rural telemedicine programs. PMID- 7790809 TI - Health care in remote areas. AB - Migration from space medicine toward telemedicine services is described by potential application areas in highly populated and remote areas of Europe. Special emphasis is laid upon links between mobile patient monitoring and health care in remote areas. Pilot projects are described for home (mobile) monitoring of newborn infants endangered by sudden infant death (SID) and adults suffering from sleep apnoea. Health care in remote areas is described by the "TeleClinic project" which will link national nodes for telemedicine services in several European states for the mobile European citizen. Another project describes the future potential of robotics for semiautonomous ultrasound diagnostics and for realtime interaction of remote experts with diagnostics and therapy. PMID- 7790807 TI - The role of medical informatics in telemedicine. AB - The role of medical informatics in telemedicine is dependent on using the power of the computerized database to not only feed patient specific information to the health care providers, but to use the epidemiological and statistical information in the data base to improve decision making and ultimately care. The computer is also a powerful tool to facilitate standardizing and monitoring of care and when applied in continuous quality improvement methodology it can enhance the improvement process well beyond what can be done by hand. The coupling of medical informatics with telemedicine allows sophisticated medical informatics systems to be applied in low population density and remote areas. PMID- 7790810 TI - Keynote address. Second NASA/Uniformed Services University of Health Science International Conference on Telemedicine, Bethesda, Maryland. PMID- 7790812 TI - T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. AB - The antigen-specific receptors of T and B lymphocytes are generated by somatic recombination between noncontiguous gene segments encoding the variable portions of these molecules. The semirandom nature of this process, while desirable for the generation of diversity, has been thought to exact a high price in terms of sterile (out-of-frame) products. Historically, the majority of T lymphocytes generated in mammals were thought to be useless, either because they generated such sterile rearrangements or because the receptors generated did not appropriately recognize self-molecules (i.e., positive and negative selection). In the studies described here, we characterize the onset of T cell receptor (TCR) alpha and beta chain gene rearrangements and quantitate their progression throughout T cell development. The results show that T cell production efficiency is enhanced through (a) rearrangement of TCR-beta chain genes early during T cell development, with selective expansion of those cells possessing in-frame rearrangements; (b) deletion of sterile rearrangements at the TCR-alpha chain locus through ordered (proximal to distal) sequential recombination; and (c) modification of nonselectable alpha/beta heterodimer specificities through generation and expression of new TCR-alpha chains. In addition, we demonstrate strict correlations between successful TCR-beta gene rearrangement, the onset of TCR-alpha gene rearrangement, rapid cell division, and programmed cell death, which together serve to maintain cell turnover and homeostasis during T cell development. PMID- 7790811 TI - Generation of immunoglobulin light chain gene diversity in Raja erinacea is not associated with somatic rearrangement, an exception to a central paradigm of B cell immunity. AB - In all vertebrate species examined to date, rearrangement and somatic modification of gene segmental elements that encode portions of the antigen combining sites of immunoglobulins are integral components of the generation of antibody diversity. In the phylogenetically primitive cartilaginous fishes, gene segments encoding immunoglobulin heavy and light chain loci are arranged in multiple clusters, in which segmental elements are separated by only 300-400 bp. In some cases, segmental elements are joined in the germline of nonlymphoid cells (joined genes). Both genomic library screening and direct amplification of genomic DNA have been used to characterize at least 89 different type I light chain gene clusters in the skate, Raja. Analyses of predicted nucleotide sequences and predicted peptide structures are consistent with the distribution of genes into different sequence groups. Predicted amino acid sequence differences are preferentially distributed in complementarity-determining versus framework regions, and replacement-type substitutions exceed neutral substitutions. When specific germline sequences are related to the sequences of individual cDNAs, it is apparent that the joined genes are expressed and are potentially somatically mutated. No evidence was found for the presence of any type I light chain gene in Raja that is not germline joined. The type I light chain gene clusters in Raja appear to represent a novel gene system in which combinatorial and junctional diversity are absent. PMID- 7790813 TI - CD43 is a murine T cell costimulatory receptor that functions independently of CD28. AB - Costimulation mediated by the CD28 receptor has been shown to play an important role in the development of a vigorous T cell immune response. Nevertheless, CD28 deficient mice can mount effective T cell-dependent immune responses. These data suggest that other costimulatory molecules may play a role in T cell activation. In a search for other costimulatory receptors on T cells, we have characterized a monoclonal antibody (mAb) that can costimulate T cells in the absence of accessory cells. Similar to CD28 antibodies, this mAb, R2/60, was found to synergize with T cell receptor engagement in inducing proliferation. Independent ligation of CD3 and the ligand recognized by R2/60 results in T cell proliferation, suggesting that the two molecules do not have to colocalize to activate the R2/60 costimulatory pathway. R2/60 does not react with CD28, and furthermore, R2/60 costimulates in a CD28-independent fashion since the mAb costimulates T cells from the CD28-deficient mice as well as wild-type mice. Expression cloning of the R2/60 antigen identified the ligand as murine CD43. Together, these data demonstrate that CD43 can serve as a receptor on T cells that can provide CD28-independent costimulation. PMID- 7790815 TI - Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum infected erythrocytes. AB - Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS. PMID- 7790814 TI - Activation of Raf-1 and mitogen-activated protein kinase in murine macrophages partially mimics lipopolysaccharide-induced signaling events. AB - Lipopolysaccharide (LPS), a highly conserved component of the outer membrane of gram-negative bacteria, stimulates macrophages to release various cytokine and eicosanoid mediators of the immune response. The mechanism by which LPS stimulates these cells is poorly characterized. One of the most rapid LPS stimulated events is the phosphorylation and activation of the p42 and p44 isoforms of mitogen-activated protein (MAP) kinase. We wished to examine the role of MAP kinase in LPS-induced signaling in murine macrophages by activating MAP kinase independently of LPS. An expression vector encoding a Raf-1:estrogen receptor (ER) chimeric protein was transfected into the murine macrophage cell line RAW 264.7. Activation of this chimeric protein (delta Raf-1:ER) by estradiol resulted in rapid and prolonged activation of MAP kinase, as expected from previous results implicating Raf-1 as an upstream activator of this signaling cascade. LPS stimulation induced accumulation of MAP kinase phosphatase 1 messenger RNA, whereas delta Raf-1:ER activation did not, perhaps accounting for the more prolonged activation of MAP kinase seen in response to delta Raf-1:ER activation. Similarly, activation of DNA binding by the transcription factor, nuclear factor (NF) kappa B, as assessed by electrophoretic mobility shift assay, occurred in response to LPS stimulation but not in response to delta Raf-1:ER activation or phorbol myristate acetate (PMA) stimulation. Using an enzyme-linked immunosorbent assay for murine tumor necrosis factor alpha (TNF-alpha), we found that LPS and PMA stimulation and delta Raf-1:ER activation induced secretion of TNF-alpha, although the amount of TNF-alpha secreted in response to delta Raf 1:ER activation and PMA stimulation was approximately 20-fold less than that secreted in response to LPS. Correspondingly, accumulation of TNF-alpha messenger RNA was weakly induced by delta Raf-1:ER activation or PMA stimulation, whereas strong induction was noted in response to LPS. These results suggest that Raf-1 or PMA activation of MAP kinase in murine macrophages is sufficient for a small amount of TNF-alpha production and secretion in the absence of NF-kappa B activation, but LPS stimulation involves additional signaling events, such as NF kappa B activation, that augment the response seen with activation of MAP kinase alone. PMID- 7790816 TI - Antigen capture and major histocompatibility class II compartments of freshly isolated and cultured human blood dendritic cells. AB - Dendritic cells (DC) represent potent antigen-presenting cells for the induction of T cell-dependent immune responses. Previous work on antigen uptake and presentation by human DC is based largely on studies of blood DC that have been cultured for various periods of time before analysis. These cultured cells may therefore have undergone a maturation process from precursors that have different capacities for antigen capture and presentation. We have now used immunoelectron microscopy and antigen presentation assays to compare freshly isolated DC (f-DC) and cultured DC (c-DC). f-DC display a round appearance, whereas c-DC display characteristic long processes. c-DC express much more cell surface major histocompatibility complex (MHC) class II than f-DC. The uptake of colloidal gold labeled bovine serum albumin (BSA), however, is greater in f-DC, as is the presentation of 65-kD heat shock protein to T cell clones. The most striking discovery is that the majority of MHC class II molecules in both f-DC and c-DC occur in intracellular vacuoles with a complex shape (multivesicular and multilaminar). These MHC class II enriched compartments (MIIC) represent the site to which BSA is transported within 30 min. Although MIIC appear as more dense structures with less MHC class II molecules in f-DC than c-DC, the marker characteristics are very similar. The MIIC in both types of DC are acidic, contain invariant chain, and express the recently described HLA-DM molecule that can contribute to antigen presentation. CD19+ peripheral blood B cells have fewer MIIC and surface MHC class II expression than DCs, while monocytes had low levels of MIIC and surface MHC class II. These results demonstrate in dendritic cells the elaborate development of MIIC expressing several of the components that are required for efficient antigen presentation. PMID- 7790818 TI - The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. AB - IP-10 is a member of the chemokine family of cytokines and is induced in a variety of cells in response to interferon gamma and lipopolysaccharide. The self aggregation common to many chemokines, including IP-10, has hindered the identification of a specific IP-10 receptor. Using an IP-10 alkaline phosphatase fusion protein that fortuitously blocks this self-aggregation, we have identified an IP-10 binding site on a variety of cells including endothelial, epithelial, and hematopoietic cells. This binding site has a Kd of 25 nM, is inhibited by recombinant murine or human IP-10, and is dependent on the presence of cell surface heparan sulfate proteoglycans (HSPG). This conclusion is based on the findings that IP-10 binding to cells is: (a) inhibited by heparin and heparan sulfate; (b) sensitive to a 1 M NaCl wash; (c) eliminated by treatment with heparinase and trypsin; and (d) absent on mutant CHO cells that do not express cell surface HSPG. Platelet factor 4 (PF4), but not IL-8, monocyte chemoattractant protein-1, RANTES, monocyte inflammatory protein (MIP)-1 alpha, or MIP-1 beta, can compete effectively with IP-10 for binding to the cell surface. Furthermore, IP-10 shares with PF4 the ability to inhibit endothelial cell proliferation (IC50 = 150 nM). These studies demonstrate specificity in the interaction of chemokines and HSPG, and they define IP-10 and PF4 as a distinct subset of chemokines sharing an HSPG-binding site and angiostatic properties. PMID- 7790817 TI - Cooperativity between the J and S elements of class II major histocompatibility complex genes as enhancers in normal and class II-negative patient and mutant B cell lines. AB - The class II major histocompatibility complex genes all contain in their proximal promoters three cis-elements called S, X, and Y that are conserved in both sequence and position, and a fourth element, J, conserved in sequence but not in position. J, X, and Y and, to some extent, S, have been shown to be functionally important in regulation of expression of these genes. In the present study, a protein factor that binds cooperatively to the S plus J elements of the promoter of the class II major histocompatibility complex gene DPA has been detected. Moreover, functional cooperativity between S and J in activation of the enhancerless -40 interferon-beta (-40 IFN-beta) promoter has been demonstrated. Finally, the latter assay appears to subdivide complementation group A of class II negative human B cell lines that includes both mutants generated in vitro and cells from patients with the bare lymphocyte syndrome (type II). In three of these cell lines, the enhancerless -40 IFN-beta promoter containing the S plus J elements was functionally active, while in the others it was inactive. PMID- 7790819 TI - Interleukin 6 is essential for in vivo development of B lineage neoplasms. AB - Interleukin (IL) 6 has been suggested to be the major cytokine responsible for proliferation of neoplastic plasma cells in both human myeloma and mouse plasmacytoma. Much of the evidence supporting this suggestion is derived from in vitro studies in which the survival or proliferation of some plasma cell tumors has been found to be IL-6 dependent. However, it remains unclear whether this dependency is the consequence of in vivo or in vitro selective pressures that preferentially expand IL-6-responsive tumor cells, or whether it reflects a critical in vivo role for IL-6 in plasma cell neoplasia. To address this question, we have attempted to induce plasma cell tumors in normal mice and in IL 6-deficient mice generated by introduction of a germline-encoded null mutation in the IL-6 gene. The results demonstrate that mice homozygous (+/+) or heterozygous (+/-) for the wild-type IL-6 allele yield the expected incidences of plasma cell tumors. In contrast, mice homozygous for the IL-6-null allele (-/-) are completely resistant to plasma cell tumor development. These studies define the essential role of IL-6 in the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies. PMID- 7790820 TI - Self tolerance to T cell receptor V beta sequences. AB - T cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V beta 8.1 and V beta 8.2 TCR proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V beta protein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks. PMID- 7790821 TI - Triglyceride-rich lipoproteins prevent septic death in rats. AB - Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis. PMID- 7790822 TI - Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda). AB - Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in neutrophils such as myeloperoxidase, elastase, and the L-1 protein complex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and their proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibodies to defensins and an infectious disease of known etiology. The association with a particular form of onchocerciasis, sowda, suggests a link between formation of autoantibodies to defensin and enhanced immune reactivity towards the parasite. PMID- 7790823 TI - Activation of CD4+ T cells in the presence of a nondepleting monoclonal antibody to CD4 induces a Th2-type response in vitro. AB - In vitro experiments using purified rat CD4+ T cells in primary and secondary mixed leukocyte cultures (MLC) have been carried out to explore the mechanism of inhibition of cell-mediated autoimmune disease in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1 isotype, completely prevents the development of the paralysis associated with experimental allergic encephalomyelitis (EAE) in Lewis rats, but does so without eliminating the encephalitogenic T cells. The in vitro experiments described in this study have shown that when CD4+ T cells were activated in the presence of the anti-CD4 mAb in a primary MLC, the synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was completely inhibited. After secondary stimulation, now in the absence of the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced compared with that observed from CD4+ T cells derived from primary cultures in which the mAb was omitted. As IL-4 and IL-13 are known to antagonize cell-mediated immune reactions, and as EAE is cell-mediated disease, the data suggest that the W3/25 mAb controls EAE by modifying the cytokine repertoire of T cells that respond to the encephalitogen. The capacity for the mAb to suppress IFN-gamma synthesis provides, in part, an explanation for this change in cytokine production. These findings are discussed in terms of what is known of the factors that determine which cytokine genes are expressed on T cell activation. Possible implications for the evolution of T cell responses in human immunodeficiency virus infection are also discussed. PMID- 7790825 TI - CD4+ beta islet cell-reactive T cell clones that suppress autoimmune diabetes in nonobese diabetic mice. AB - We report the isolation of a panel of CD4+ T helper type 1 autoreactive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cell clones express a diverse repertoire of T cell receptors, three of which recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capacity of the T cell clones correlates with their ability to produce a novel immunoregulatory activity that potently inhibits in vitro allogeneic mixed lymphocyte reaction. The partially purified activity significantly inhibited the adoptive transfer of diabetes. Our work provides evidence in support of the existence of T helper type 1, CD4+ T cells reactive to beta islet cell autoantigens that have acquired a protective instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of down-regulating immune responses, and they are likely to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance. PMID- 7790827 TI - Perceptual load as a necessary condition for selective attention. AB - The early and late selection debate may be resolved if perceptual load of relevant information determines the selective processing of irrelevant information. This hypothesis was tested in 3 studies; all used a variation of the response competition paradigm to measure irrelevant processing when load in the relevant processing was varied. Perceptual load was manipulated by relevant display set size or by different processing requirements for identical displays. These included the requirement to process conjunctions versus isolated features and the requirement to perform simple detection of a character's presence versus difficult identification of its size and position. Distractors' interference was found only under low-load conditions. Because the distractor was usually clearly distinct from the target, it is concluded that physical separation is not a sufficient condition for selective perception; overloading perception is also required. This allows a compromise between early and late selection views and resolves apparent discrepancies in previous work. PMID- 7790824 TI - Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor. AB - Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0 beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism. PMID- 7790826 TI - Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses. AB - We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild-type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin. PMID- 7790828 TI - Role of the syllable in the processing of spoken English: evidence from a nonword comparison task. AB - Previous research using monitoring tasks suggests that syllables do not play a role in the initial processing of speech by English listeners. The role of syllables in a different task, one involving the speeded comparison of 2 nonwords, was investigated. In 2 experiments, responses to nonword pairs that shared a complete syllable were significantly faster than responses to pairs that shared part of a syllable when the shared unit was at the beginning or in the middle of the nonwords. Results were mixed when the shared unit was at the end of the nonwords, possibly reflecting a confounding effect of rhyme. Findings suggest that syllabified representations of the nonwords may be used in a comparison task, even in English. Results are interpreted relative to different demands of the nonword comparison and monitoring tasks. PMID- 7790829 TI - Calibration of human locomotion and models of perceptual-motor organization. AB - People coordinate the force and direction of skilled actions with target locations and adjust the calibrations to compensate for changing circumstances. Are the adjustments globally organized (adjusting a particular action to fit a particular circumstance would generalize to all actions in the same circumstance); anatomically specific (every effector is adjusted independently of others); of functional (adjustments would generalize to all actions serving the same goal and generating the same perceptible consequences)? Across 10 experiments, changes in the calibration of walking, throwing, and turning-in place were induced, and generalization of changes in calibration to functionally related and unrelated actions were tested. The experiments demonstrate that humans rapidly adjust the calibration of their walking, turning, and throwing to changing circumstances, and a functional model of perceptual-motor organization is suggested. PMID- 7790830 TI - Strategies and mechanisms in nonselective and selective inhibitory motor control. AB - Motor inhibition was studied in 3 versions of the stop-signal paradigm, with the stop signal requiring inhibition of any response (stop-all), a fixed alternative response (stop-change), or selective inhibition of only 1 of the responses (selective-stop). The lateralized readiness potential was used in Experiment 1 to distinguish between a selective, central, and a global peripheral inhibition mechanism. Inhibition was found to be effected by the central mechanism in the stop-change condition and by the peripheral mechanism in the other conditions. Manipulation of stimulus discriminability in Experiment 2 strongly affected the speed of selective motor inhibition, confirming that such inhibition was achieved by conditionally engaging the peripheral mechanism. These results support the idea that functionally distinct mechanisms and strategies are involved in inhibitory motor control in different situations. PMID- 7790831 TI - Perceiving exterior letters of words: differential influences of letter-fragment and non-letter-fragment masks. AB - Previous research shows letter-fragment masks and non-letter-fragment fields have different effects on performance with briefly presented alphabetic targets. However, popular accounts of these differences ignore mask configuration. Over a series of experiments, configurational effects of letter-fragment (LF) and non letter-fragment (NLF) masks were compared. When the configuration of LF masks matched word boundaries, performance with exterior letter pairs from words improved, whereas performance with illegal exterior-letter pairs and single letters was unaffected. When the same changes were made to NLF masks, only an overall drop in performance occurred, with no selective effect on target type. Thus, although LF mask configuration selectively affected lexical processing, NLF mask configuration produced substantially different effects, indicating problems with contemporary accounts of masking differences that ignore influences of mask configuration. PMID- 7790833 TI - Does mental rotation require central mechanisms? AB - Four reaction time experiments examined the mental rotation process using a psychological refractory period paradigm. On each trial, participants made speeded responses to both a tone (S1) and a rotated letter (S2), presented with varying stimulus onset asynchronies (SOAs). If mental rotation of the stimulus letter can proceed while central mechanisms are busy with S1, then the effect of orientation should decrease substantially with decreasing SOA. Contrary to these predictions, the effect of orientation was nearly constant across SOAs, suggesting that mental rotation cannot effectively proceed without help from central mechanisms. These results support the conclusion that mental rotation requires access to a single-channel mechanism and must therefore be performed serially with other operations requiring the same mechanism. PMID- 7790834 TI - Competing global and local completions in visual occlusion. AB - In visual occlusion 2 amodal-completion tendencies occur frequently. One tendency leads toward the simplest completed shape (a global completion) and the other to a shape for which the completion itself is as simple as possible (a local completion). Two experimental paradigms were used to test the strengths of these completion tendencies: a drawing task and a simultaneous matching task. The experimental results support the notion that the preference for either a global or a local completion is the consequence of a competition between interpretations. Finally, the authors discuss how the preference for a completion can be predicted by a model that is based on a quantification of both global and local aspects. PMID- 7790835 TI - Automatic access to object identity: attention to global information, not to particular physical dimensions, is important. AB - The authors examined whether, by attending to physical properties of objects, participants can prevent the activation of semantic information. Participants received a reference object followed by a display containing both a matching target and a distractor. In Experiments 1 and 2, participants attended to motion and to surface texture, respectively. Some evidence for the processing of semantic information occurred. This result contrasted with a previous study in which no evidence for semantic information processing was apparent in a color matching task (M. Boucart & G.W. Humphreys, 1994). In Experiment 3, pictures were used with outline contours composed of randomly distributed red and green dots, one color being overrepresented. Participants matched pictures according to the dominant color. Evidence for semantic processing emerged. The authors suggest that these results cannot be explained in terms of attention operating differently on separate physiological channels. Instead it is proposed that what is crucial in activating stored object representations is whether the global configuration of the picture is processed. PMID- 7790832 TI - Second-order parallel processing: visual search for the odd item in a subset. AB - Visual search tasks in which participants searched for an odd element in a subset of items were investigated. Participants searched for an item of odd orientation in the red subset. The target was a red line of X degree, distractors were green lines of X degree and red lines of Y degree. The orientations, X and Y, changed on every trial. In this task, orientation information was useful only after color had been used to select the relevant subset. Results show that response time (RT) and error data were different from standard color X orientation conjunction searches (Experiment 1). RT x Set Size functions had slopes near 0 ms per item (Experiment 2). The selection of the subset appeared to take 200-300 ms (Experiments 2 and 3). Subset selection was based on properties of the relevant subset, not the irrelevant subset (Experiment 4). It was more difficult (perhaps impossible) to select a subset defined by 2 colors (Experiment 5). Random variation in an irrelevant dimension did not disrupt subset search (Experiment 6). PMID- 7790836 TI - Temporal rescaling of sample and complex rations in rhythmic tapping. AB - Two well-established phenomena in temporal performance--preference for simple ratios over complex ratios and the ability to proportionately rescale temporal patterns--were examined together. Unlike the case with simple ratios, participants (3 trained musicians) showed only a limited ability to learn complex ratios and no ability to proportionately rescale them. These differences suggest that different mechanisms are used to produce the 2 ratio types. Systematic biases observed in the performances of the simple ratios (6 trained musicians) were modeled by assuming that an additive timing component, which is unequal for short and long intervals and changes with base rate, overlays a system that preferentially produces simple ratios. The general pattern of results was consistent with the view that rhythmic learning builds on or modifies a system of innate preferences. PMID- 7790839 TI - Similarity determines the attentional blink. AB - When participants are required to respond to a target letter imbedded in a stream of rapid serially presented letters, perception of a 2nd target letter is impaired if the interval between the 2 targets is less than about 450 ms. This attentionally based posttarget suppression in visual processing, referred to as the attentional blink (AB), is not found when there is a brief pause in the stream immediately after the 1st target. To investigate the importance of posttarget stimulation in AB production, the categorical, featural, and spatial similarity of the immediate posttarget item to other items in the stream was manipulated. Although featural and spatial dissimilarity produced significant attenuation of the AB effect, categorical dissimilarity did not. Significant AB effects were found in all conditions, suggesting that the presentation of any patterned stimulus in close temporal proximity to the target provokes the AB. PMID- 7790838 TI - Auditory coding, cues, and coherence in phonetic perception. AB - C. T. Best, M. Studdert-Kennedy, S. Manuel, and J. Rubin-Spitz (1989) reported that listeners given speech labels showed categorical-like perception of a series of complex tone analogs to a /la/-/ra/ speech series, whereas nonspeech listeners were unable to classify the stimuli consistently. In 2 experiments, a new training and testing procedure was used with adult listeners given nonspeech instructions. They classified the /la/-/ra/ tone analogs consistently, showed categorical-like perception, and generalized their training to a new, /li/-/ri/ tone analog series. Two sets of auditory attributes were described for coding the /l/-/r/ distinction, and 1 was shown to quantitatively predict listeners' classification of both series. These results are consistent with models of perception in which a rich, abstract auditory code is computed and forms the basis for both speech and nonspeech auditory categories. PMID- 7790837 TI - What causes the face inversion effect? AB - What is it about the way faces are represented by the visual system that makes them so much harder to recognize when inverted? The authors tested the hypothesis that the "face inversion" effect results from the use of holistic shape representations. This suggests that the susceptibility of nonface patterns to inversion should be a function of their degree of part decomposition. In Experiment 1 this was tested and confirmed with dot patterns in which the degree of part decomposition was manipulated by grouping and segregation on the basis of dot color. The hypothesis also predicted that the face inversion effect can be eliminated with face stimuli if participants are induced to recognize the faces in terms of their component parts. In Experiment 2 this was tested and confirmed with whole, intact faces, in which the degree of part decomposition was manipulated by allowing participants to study them, initially, in either whole, intact versions or versions with parts presented separately. PMID- 7790840 TI - Systematic distortion of perceived three-dimensional structure from motion and binocular stereopsis. AB - The geometric relation between physical and perceived space as specified by binocular stereopsis and structure from motion was investigated. Four experimental tasks were used, each of which required a different aspect of three dimensional (3-D) structure to be performed accurately. To examine whether the transformation between physical and perceptual space preserved the 3-D structural properties required to perform each of our tasks, the constancy of judged shape over changes in a depicted object's viewing distance or orientation was examined. Our results reveal that observers' judgments of 3-D shape from binocular stereopsis and motion contained systematic distortions: Perceived 3-D shape from motion was not invariant over orientation change and perceived 3-D structure from stereo, and motion and stereo in combination was not invariant over changes in viewing distance. PMID- 7790841 TI - Comparing depth from motion with depth from binocular disparity. AB - The accuracy of depth judgments that are based on binocular disparity or structure from motion (motion parallax and object rotation) was studied in 3 experiments. In Experiment 1, depth judgments were recorded for computer simulations of cones specified by binocular disparity, motion parallax, or stereokinesis. In Experiment 2, judgments were recorded for real cones in a structured environment, with depth information from binocular disparity, motion parallax, or object rotation about the y-axis. In both of these experiments, judgments from binocular disparity information were quite accurate, but judgments on the basis of geometrically equivalent or more robust motion information reflected poor recovery of quantitative depth information. A 3rd experiment demonstrated stereoscopic depth constancy for distances of 1 to 3 m using real objects in a well-illuminated, structured viewing environment in which monocular depth cues (e.g., shading) were minimized. PMID- 7790842 TI - Effects of annetocin, an oxytocin-related peptide isolated from the earthworm Eisenia foetida, and some putative neurotransmitters on gut motility of the earthworm. AB - Annetocin, an oxytocin-related peptide recently isolated from the lumbricid earthworm Eisenia foetida, and putative transmitter substances were examined for their effects on rhythmic, spontaneous contractions of isolated gut preparations of the earthworm. Significant, dose-dependent effects of the following substances were observed: acetylcholine (ACh), gamma-aminobutyric acid (GABA), and dopamine were excitatory, while serotonin (5-HT) and octopamine were inhibitory. Annetocin, oxytocin, and vasotocin stimulated spontaneous contraction of the earthworm gut, annetocin being approximately 10-fold more potent than oxytocin or vasotocin. However, arginine-vasopressin (Arg-vasopressin), lysine-vasopressin (Lys-vasopressin), tocinoic acid (N-terminal hexapeptide fragment of oxytocin), and MSH release-inhibiting factor (MIF; C-terminal tripeptide fragment of oxytocin) did not show any effect on the earthworm gut motility. On the other hand, oxytocin, vasotocin, Arg-vasopressin, Lys-vasopressin, and tocinoic acid caused spontaneous contractions of isolated rat uterine preparations, where the potency was in this order, while annetocin and MIF exerted no oxytocic activity on the uterus. Dose-response relationship of the effects of annetocin and its related peptides on the annelid and mammalian systems shows that amino acid residue at the third position of these peptides is important for exertion of excitatory action on the smooth muscle systems. The results in the present study suggest that receptors for annetocin and for GABA on the earthworm gut, unlike those for ACh, desensitize during continuous exposure to these substances. PMID- 7790843 TI - Freezing of zona-free mouse embryos: characteristics of the plasma membrane and subsequent development of the embryos. AB - Frozen-thawed mouse embryos with (+ZP) and without (-ZP) zona pellucida have been studied at the Scanning Electron Microscope (SEM) to determine how the process affects the plasma membrane and the subsequent embryo development. The main difference observed in -ZP embryos immediately after thawing is the abnormal morphology and distribution of microvilli. This could explain the spontaneous separation of blastomeres in -ZP embryos, and the decrease in their survival rate. If thawed -ZP embryos are allowed to recover in culture, their plasma membrane characteristics and survival rate are identical to those of control embryos. PMID- 7790844 TI - Expression of osteopontin in the head process late in gastrulation in the rat. AB - Osteopontin (OPN) is a secreted, glycosylated phosphoprotein. Previous studies have implicated OPN in calcification/decalcification and inflammation. We became interested in developmental expression of OPN because of our previous findings that suggest OPN may play a role in formation of new vascular layers after injury, and because of our observation of developmental regulation in vascular smooth muscle cells. While OPN was expressed at low levels in vessels, only late in development, examination of very early expression patterns revealed a surprising finding. OPN was expressed exclusively in the head process, on day 9.0 late in gastrulation in the rat. In vitro studies of vascular smooth muscle cells have previously demonstrated that OPN promotes cell adhesion and migration. It is suggested that OPN may promote migration of cells, during gastrulation, via integrins which may be present in the head process or overlying ectoderm. PMID- 7790845 TI - Replicating DNA does not block germinal vesicle breakdown in mouse oocytes. AB - Mouse germinal vesicle GV-G2 stage oocytes were fused to very early S-phase blastomeres from four cell stage embryos to test whether oocytes have a mechanism which detects replicating DNA and thereafter arrests meiosis at the GV stage. Our results show that oocytes are unable to recognize replicating DNA in transplanted nuclei and undergo germinal vesicle breakdown (GVBD). GVBD and blastomere nucleus breakdown are only blocked by inhibitors of both oocyte maturation and DNA synthesis. These results show that mouse immature oocytes do not possess a feedback control capable of detecting replicating DNA. PMID- 7790846 TI - Effects of relative area on matching heterochromatic stimuli for saturation. AB - Participants adjusted the saturation of one rectangular color stimulus so that it appeared to match the saturation of another rectangular color stimulus for stimulus pairs of different relative areas. In Experiment 1, in which stimuli of complementary colors were used, higher saturation stimuli were consistently chosen for large areas to match lower saturation stimuli in smaller areas. In Experiment 2, better saturation matches were obtained if participants fixated and the stimuli were presented for very brief durations. In Experiment 3, larger color contrast effects were obtained with hue pairs that were nearer to complementary than with hue pairs that were more nearly the same. These findings agree with the interpretation that biases in relative saturation selected to match stimuli of different relative size are largely the result of negative afterimages of the larger stimulus having greater impact on the apparent saturation of the smaller stimulus. PMID- 7790848 TI - Increasing- and decreasing-loudness aftereffects: asymmetrical functions for absolute rate of sound level change in adapting stimulus. AB - After exposure to a tone of decreasing sound level, participants report that a steady tone increases in loudness; after exposure to an increasing sound level, they perceive a steady tone to decrease in loudness. The increasing-loudness aftereffect is the more sensitive to a difference between adapting and test frequencies, its absolute size becoming greater than that for decreasing-loudness aftereffect as frequencies are made to match. Although this asymmetry may reflect processing differences for the two directions of sound level change, a more parsimonious hypothesis entails perceived increasing loudness of short steady tones, in conjunction with differing levels of tonal adaptation across test frequencies. The former explanation is supported by the present report of another aftereffect asymmetry: With frequency the same for both adapting and test stimuli, so that tonal adaptation was nearly asymptotic during testing, altering the absolute rate of sound level change of the adapting stimulus had a greater effect on the magnitude of the increasing-loudness aftereffect. The first hypothesis is consistent with the percussive nature of natural sounds, few of which are steady: most of their sound levels rise almost instantaneously and decrease slowly. PMID- 7790847 TI - Feeling the parts: a developmental study of separable perception with tactile dimensions. AB - A tetrad classification task was used to determine perceptual sensitivity to the tactile dimensions of texture, hardness, and shape in 5- and 11-year-old children who classified objects by touch, unaided by vision. Both age groups reliably used separate dimensions to group the objects. Both age-related and individual differences in dimensional salience were observed. Five-year-olds predominantly grouped objects that were identical in hardness; 11-year-olds most often grouped objects identical in hardness or shape. Overall (integral) similarity was not used reliably by any participant. Results support the differential-sensitivity view of cognitive development and are consistent with Garner's (1970) distinction between integral and separable stimulus structure, but they do not support the hypothesized developmental trend from integral to separable perception. PMID- 7790849 TI - Retrieval of inedible objects by Norway rats after habituation of gnawing: resistance to satiation? AB - Retrieval of wooden blocks by Norway rats was tested after continuous exposure to these objects sufficient to reduce gnawing. In two experiments rats were first allowed to retrieve during restricted daily trials. Then they were exposed to blocks in their home cages, and at some point during exposure they were retested in the retrieval situation. In Experiment 1, further retrieval tests were given beginning the day after blocks were introduced in the cages. In Experiment 2, rats were exposed to blocks for 100 days before they were retested for retrieval. In both experiments, amount of retrieval was minimally affected by exposure, although gnawing was significantly depressed. This contrasts with earlier work, which showed that habituation of gnawing in the cage was followed by a significant decline in retrieval. The major qualitative difference between this and past work was that rats in the present experiments were allowed to retrieve the blocks before continuous exposure to them. The author concluded that retrieval experience may lead to persistence of retrieval despite a decline in incentive value of the objects retrieved, indicated by the decline in gnawing, and he discusses relations to other demonstrations of persistence in the absence of original motivational conditions-in particular, "resistance to satiation" effects. PMID- 7790850 TI - Visual field tunneling in aviators induced by memory demands. AB - Aviators are required rapidly and accurately to process enormous amounts of visual information located foveally and peripherally. The present study, expanding upon an earlier study (Williams, 1988), required young aviators to process within the framework of a single eye fixation a briefly displayed foveally presented memory load while simultaneously trying to identify common peripheral targets presented on the same display at locations up to 4.5 degrees of visual angle from the fixation point. This task, as well as a character classification task (Williams, 1985, 1988), has been shown to be very difficult for nonaviators: It results in a tendency toward tunnel vision. Limited preliminary measurements of peripheral accuracy suggested that aviators might be less susceptible than nonaviators to this visual tunneling. The present study demonstrated moderate susceptibility to cognitively induced tunneling in aviators when the foveal task was sufficiently difficult and reaction time was the principal dependent measure. PMID- 7790852 TI - Identification of new oligodendrocyte- and myelin-specific genes by a differential screening approach. AB - We have isolated several new genes that are specifically expressed by oligodendrocytes in the CNS. This was achieved by differential screening of a rat spinal cord cDNA library with probes derived from normal and from oligodendrocyte free spinal cord mRNAs. Four of these genes are exclusively expressed by oligodendrocytes: Three of these are not related to known genes, whereas one encodes the myelin oligodendrocyte glycoprotein (MOG). Four other genes are expressed by oligodendrocytes as well as by Schwann cells. One gene codes for apolipoprotein D, which is thought to be involved in lipid metabolism. A second cDNA sequence codes for the recently identified galactosylceramide-synthesizing enzyme UDP-galactose:ceramide galactosyltransferase. The third gene encodes a small protein with four putative transmembrane domains that is related to a T lymphocyte-specific membrane protein, MAL. The fourth gene encodes the rat homologue of the stearyl-CoA-desaturase 2 (SCD2) gene, which is specifically expressed in the nervous system and involved in the synthesis and regulation of long-chain unsaturated fatty acids essential for myelination. Finally, we found that a member of the beta-tubulin family is highly expressed in oligodendrocytes as well as neurons. The identification of several new proteins that may play a role in myelin synthesis and sheath formation will lead to new insight into this complex mechanism. PMID- 7790851 TI - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide potentiate c-fos expression induced by glutamate in cultured cortical neurons. AB - Previous reports have demonstrated that glutamate stimulates c-fos mRNA expression in primary cultures of mouse cerebral cortical neurons. We show here that vasoactive intestinal peptide (VIP) induces c-fos mRNA expression; however, this effect of VIP is completely inhibited by the noncompetitive NMDA receptor antagonist MK-801, therefore indicating that VIP stimulates c-fos expression in a glutamate-dependent manner. A similar effect was observed with pituitary adenylate cyclase-activating polypeptide27 (PACAP27). At the intracellular level, coactivation of protein kinases A and C mediates the glutamate-dependent stimulation of c-fos expression evoked by VIP, because either H-89 or staurosporin inhibits the effect of VIP as well as that of glutamate. These results point to a "biochemical AND gate" mechanism, which implies the obligatory activation of both protein kinases A and C in the transduction of c-fos expression. In summary, this article provides evidence that VIP and PACAP27 potentiate the effect of glutamate, the principal effector on c-fos expression, suggesting that both peptides can increase the "throughput" or "strength" of glutamate-containing circuits in the cerebral cortex. PMID- 7790853 TI - Allosteric interactions among agonists and antagonists at 5-hydroxytryptamine3 receptors. AB - Cooperation in the action of agonists suggests that there are multiple binding sites on 5-hydroxytryptamine3 (5-HT3) receptors. The purpose of this study was to characterize these binding sites and their interactions on both native and cloned 5-HT3 receptors. The affinities of competitive 5-HT3 receptor antagonists were similar regardless of whether the receptors were labeled with [3H]RS-42358, [3H]granisetron, or 1-(m-[3H]chlorophenyl)biguanide ([3H]mCPG). By contrast, the affinities of the agonists 5-HT, mCPG, and phenylbiguanide were approximately 10 fold higher when the receptors were labeled with [3H]mCPG. The dissociation of [3H]mCPG, [3H]RS-42358, and [3H]RS-25259, but not [3H]granisetron, from both cloned and native 5-HT3 receptors was markedly slower in the presence of 5-HT or 2-methyl-5-HT than in the presence of antagonists such as RS-42358. This suggests that the binding of these agonists to unoccupied sites on the receptor can increase the receptor's affinity for prebound ligands and thereby slow their dissociation. These data support previous indications of positive cooperation among multiple binding sites on both native and cloned 5-HT3 receptors, and they extend this idea by demonstrating that agonists can modify the interaction of some, but not all, antagonists with the receptor. PMID- 7790854 TI - Local influence of endogenous norepinephrine on extracellular dopamine in rat medial prefrontal cortex. AB - Noradrenergic and dopaminergic projections converge in the medial prefrontal cortex and there is evidence of an interaction between dopamine (DA) and norepinephrine (NE) terminals in this region. We have examined the influence of drugs known to alter extracellular NE on extracellular NE and DA in medial prefrontal cortex using in vivo microdialysis. Local application of the NE uptake inhibitor desipramine (1.0 microM) delivered through a microdialysis probe increased extracellular DA (+149%) as well as NE (+201%) in medial prefrontal cortex. Furthermore, desipramine potentiated the tail shock-induced increase in both extracellular DA (stress alone, +64%; stress + desipramine, +584%) and NE (stress alone, +55%; stress + desipramine, +443%). In contrast, local application of desipramine did not affect extracellular DA in striatum, indicating that this drug does not influence DA efflux directly. Local application of the alpha 2 adrenoceptor antagonist idazoxan (0.1 or 5.0 mM) increased extracellular NE and DA in medial prefrontal cortex. Conversely, the alpha 2-adrenoceptor agonist clonidine (0.2 mg/kg; i.p.) decreased extracellular NE and DA in medial prefrontal cortex. These results support the hypothesis that NE terminals in medial prefrontal cortex regulate extracellular DA in this region. This regulation may be achieved by mechanisms involving an action of NE on receptors that regulate DA release (heteroreceptor regulation) and/or transport of DA into noradrenergic terminals (heterotransporter regulation). PMID- 7790856 TI - Effects of chronic lithium treatment on agonist-enhanced extracellular concentrations of cyclic AMP in the dorsal hippocampus of freely moving rats. AB - Studies on brain slices and homogenates suggest that chronic lithium treatment affects the activity of adenylate cyclases in the brain. To investigate whether chronic lithium administration influences the cyclic AMP (cAMP) synthesis in vivo, we have used microdialysis to assess lithium-induced alterations in extracellular concentrations of cAMP in the dorsal hippocampus of freely moving rats. Local infusion of noradrenaline or forskolin through the microdialysis probes produced rapid increases in the extracellular concentrations of cAMP in the dorsal hippocampus. Lithium administration for 4 weeks (serum lithium concentration of 0.8 +/- 0.11 mmol/L) did not affect the baseline levels of cAMP. However, in rats fed a lithium-supplemented diet, noradrenaline- and forskolin induced enhancement of cAMP levels was decreased in the dorsal hippocampus. The rats were video-taped 18 min before and 27 min after initiating the introduction of noradrenaline and forskolin into the dorsal hippocampus. The infusion of agonists induced a moderate behavioural excitation. Rats treated with lithium were less active compared with the control rats. Taken together, these data confirm that chronic lithium administration affects the cAMP signaling system in the brain of living animals, presumably by interfering with a site beyond the receptor level. PMID- 7790855 TI - Differential regulation of D1 dopamine receptor- and of A2a adenosine receptor stimulated adenylyl cyclase by mu-, delta 1-, and delta 2-opioid agonists in rat caudate putamen. AB - Inhibition and stimulation of adenylyl cyclase by opioid and D1 dopamine or A2a adenosine agonists, respectively, were characterized in the caudate putamen of rats. D1 dopamine receptors have been reported to be localized preferentially on striatonigral neurons and A2a adenosine receptors on striatopallidal neurons. The aim of the present study was to evaluate the effects of mu-[Tyr-D-Ala-Gly-(N Me)Phe-Gly-ol (DAMGO)], delta 1-[Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE)], and delta 2- ([D-Ala2]deltorphin-II [DT-II]) opioid agonists on the D1 dopamine receptor- and A2a adenosine receptor-stimulated adenylyl cyclase in membranes from rat caudate putamen. The results show that DAMGO, DPDPE, and DT-II inhibit forskolin stimulated adenylyl cyclase [selectively antagonized by D-Phe-Cys-Tyr-D-Trp-Orn Thr-Pen-Thr-NH2 (CTOP; mu antagonist), 7-benzylidenenaltrexone (BNTX; delta 1 antagonist), and naltriben (NTB; delta 2 antagonist), respectively], but only mu- and delta 2-opioid agonists inhibit D1 dopamine-stimulated adenylyl cyclase (antagonized by CTOP and NTB, respectively). Furthermore, DT-II and DPDPE inhibit A2a adenosine-stimulated adenylyl cyclase (antagonized by NTB and BNTX, respectively), whereas DAMGO did not inhibit A2a adenosine-stimulated adenylyl cyclase activity. These results suggest that mu-, delta 1-, and delta 2-opioid receptors display differential localization and provide neurochemical evidence suggesting the differential location of the delta 1 and delta 2 subtypes. mu Opioid receptors may be preferentially expressed by striatonigral neurons, delta 1-by striatopallidal neurons, and delta 2-by these two striatal efferent neuron populations. PMID- 7790857 TI - Receptor-mediated desensitisation of histamine H1 receptor-stimulated inositol phosphate production and calcium mobilisation in GT1-7 neuronal cells is independent of protein kinase C. AB - GT1-7 cells, a clonal line derived from specific tumours of gonadotropin releasing hormone-secreting neurons from mouse hypothalamus, were used as a model system to investigate the cellular mechanisms underlying the histamine H1 receptor-mediated desensitisation. GT1-7 cells contain H1 receptors, acute stimulation of which leads to the desensitisation of histamine-mediated calcium mobilisation and is manifest as a concurrent reduction in both the magnitude of the calcium transient and of the sustained phase. Acute pretreatment of the cells with the phorbol ester, phorbol 12-myristate 13-acetate, can also ablate the histamine-stimulated calcium mobilisation. In addition, acute H1-receptor stimulation and acute phorbol ester treatment result in the attenuation of histamine-mediated inositol phosphate production. Receptor desensitisation resulting from acute stimulation with histamine is not affected by inhibiting protein kinase C (PKC) activity with Ro 31-7549 or staurosporine. In contrast, the desensitisation of H1-receptor responses induced by direct activation of protein kinase C is preventable by PKC inhibitors. Thus, these results imply that a PKC-dependent mechanism and PKC-independent mechanism are involved in the H1 receptor desensitisation cascade in GT1-7 cells and do not support the involvement of PKC in the receptor-mediated desensitisation of H1 receptor stimulated calcium and inositol phosphate responses. PMID- 7790858 TI - Demonstration of kappa 3-opioid receptors in the SH-SY5Y human neuroblastoma cell line. AB - In addition to the mu- and delta-opioid receptors previously reported, the SH SY5Y human neuroblastoma cell line has high levels of kappa 3 receptors, accounting for 40% of total opioid binding, as measured with [3H]-diprenorphine binding. Competition studies reveal binding profiles for all three receptor classes that are similar to those observed in brain membranes. Differentiation with retinoic acid increases the levels of opioid receptor binding in the cell line, with the largest elevations in kappa 3 binding. Fully 75% of the increased binding corresponds to kappa 3 sites, which represent 50% of total opioid receptor binding in differentiated cells. Morphine inhibits forskolin-stimulated cyclic AMP accumulation, and this effect is readily blocked by the mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Naloxone benzoylhydrazone, a kappa 3 agonist, inhibits forskolin-stimulated cyclic AMP accumulation more potently than morphine and is not reversed by CTAP. These studies indicate that SH-SY5Y cells contain high levels of functional kappa 3 receptors. PMID- 7790860 TI - Biochemistry of somatodendritic dopamine release in substantia nigra: an in vivo comparison with striatal dopamine release. AB - The somatodendritic release of dopamine in substantia nigra previously has been suggested to be nonvesicular in nature and thus to differ from the classical, exocytotic release of dopamine described for the dopaminergic nerve terminal in striatum. We have compared the effects of reserpine, a compound that disrupts vesicular sequestration of monoamines, on the storage and release of dopamine in substantia nigra and striatum of rats. Reserpine administration (5 mg/kg, i.p.) significantly decreased the tissue level of dopamine in substantia nigra pars reticulata, substantia nigra pars compacta, and striatum. In these brain areas, reserpine-induced reductions in tissue dopamine level occurred within 2 h and persisted at 24 h postdrug. In vivo measurements using microdialysis revealed that reserpine administration rapidly decreased the extracellular dopamine concentration to nondetectable levels in substantia nigra as well as in striatum. In both structures, it was observed that reserpine treatment significantly attenuated the release of dopamine evoked by a high dose of amphetamine (10 mg/kg, i.p.) given 2 h later. In contrast, dopamine efflux in response to a low dose of amphetamine (2 mg/kg, i.p.) was not altered by reserpine pretreatment either in substantia nigra or in striatum. The present data suggest the existence, both at the somatodendritic and at the nerve terminal level, of a vesicular pool of dopamine that is the primary site of transmitter storage and that can be displaced by high but not low doses of amphetamine. The physiological release of dopamine in substantia nigra and in striatum is dependent on the integrity of this vesicular store. PMID- 7790859 TI - Characterization of NMDA receptor subunit-specific antibodies: distribution of NR2A and NR2B receptor subunits in rat brain and ontogenic profile in the cerebellum. AB - Selective antisera for NMDA receptor subunits NR2A and NR2B have been developed. Each antiserum identifies a single band on an immunoblot at approximately 175 kDa that appears to be the appropriate subunit of the NMDA receptor. Using these antisera the relative densities of the subunits in eight areas of adult rat brain have been determined. The NR2A subunit was found to be at its highest level in hippocampus and cerebral cortex, to be at intermediate levels in striatum, olfactory tubercle, mid-brain, olfactory bulb, and cerebellum, and to be at lowest levels in the pons-medulla. The NR2B subunit was found to be expressed at its highest levels in the olfactory tubercle, hippocampus, olfactory bulb, and cerebral cortex. Intermediate levels were expressed in striatum and mid-brain, and low levels were detected in the pons-medulla. No signal for NR2B was found in the cerebellum. These regional distributions were compared with that for [3H]MK 801 binding sites. It was found that although the distribution of the NR2A subunit corresponds well with radioligand binding, the distribution of the NR2B subunit does not. The ontogenic profiles of NR2A and NR2B subunits in the rat cerebellum were also determined. Just following birth [postnatal day (P) 2] NR2A subunits are undetectable, whereas NR2B subunits are expressed at amounts easily measurable. Beginning at about P12 the levels of NR2A rise rapidly to reach adult levels by P22. At the same time (P12), levels of NR2B protein begin to decline rapidly to reach undetectable levels by 22 days after birth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790861 TI - In vivo assessment of dopamine uptake in rat medial prefrontal cortex: comparison with dorsal striatum and nucleus accumbens. AB - In vivo electrochemistry was used to characterize dopamine clearance in the medial prefrontal cortex and to compare it with clearance in the dorsal striatum and nucleus accumbens. When calibrated amounts of dopamine were pressure-ejected into the cortex from micropipettes adjacent to the recording electrodes, transient and reproducible dopamine signals were detected. The local application of the selective uptake inhibitors GBR-12909, desipramine, and fluoxetine before the application of dopamine indicated that at the lower recording depths examined (2.5-5.0 mm below the brain surface), locally applied dopamine was cleared from the extracellular space primarily by the dopamine transporter. The norepinephrine transporter played a greater role at the more superficial recording sites (0.5 2.25 mm below the brain surface). To compare clearance of dopamine in the medial prefrontal cortex (deeper sites only), striatum, and nucleus accumbens, varying amounts of dopamine were locally applied in all three regions of individual animals. The signals recorded from the cortex were of greater amplitude and longer time course than those recorded from the striatum or accumbens (per picomole of dopamine applied), indicating less efficient dopamine uptake in the medial prefrontal cortex. The fewer number of transporters in the medial prefrontal cortex may be responsible, in part, for this difference, although other factors may also be involved. These results are consistent with the hypothesis that regulation of dopaminergic function is unique in the medial prefrontal cortex. PMID- 7790862 TI - The CCK-B antagonist CI-988 increases dopamine levels in microdialysate from the rat nucleus accumbens via a tetrodotoxin- and calcium-independent mechanism. AB - CI-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI-988 perfusion and returned to baseline levels upon cessation of CI-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of CI-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular. PMID- 7790863 TI - The intracellular component of cellular 3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) reduction is specifically inhibited by beta amyloid peptides. AB - In vitro cell culture model systems for investigating the biochemical mechanisms involved in the neurodegenerative actions of beta-amyloid peptide (beta-AP) have been established. Using rat pheochromocytoma PC12 or human epitheloid HeLa cell lines, submicromolar concentrations of the beta-AP fragments beta 1-40, beta 1 39, and beta 25-35, but not beta 1-28, were found to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). In both cell lines, the beta-AP-sensitive component represented approximately 70% of total cellular MTT reduction. When the reduction of a series of structurally related dyes was compared with that of MTT, the reduction of 3 alpha-naphthyl-2 phenyl-5-(4-nitrophenyl)-2H-tetrazolium chloride (NTV) was also found to be sensitive to beta 25-35, but that of seven other redox dyes was not. A property common to MTT and NTV is that they are both readily taken up into PC12 and HeLa cells and do not require an artificial electron coupling agent to be reduced. Microscopic analysis of MTT-formazan product formation in PC12 and HeLa cells following beta 25-35 treatment revealed that it was the intracellular component of the reduction of this dye that was abolished. These results support the hypothesis that the cellular reduction of MTT represents a specific indicator of the initial events underlying the mechanism of beta-AP toxicity. PMID- 7790864 TI - Overexpression of the neurotrophic cytokine S100 beta in human temporal lobe epilepsy. AB - Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100 beta is an astrocyte-derived cytokine that promotes neurite growth and induces increases in levels of intracellular calcium in neurons. In sections of neocortex of surgically resected temporal lobe tissue from patients with intractable epilepsy, we found that the number of S100 beta-immunoreactive astrocytes was approximately threefold higher than that found in control patients (p < 0.001). These astrocytes were activated, i.e., enlarged, and had prominent processes. Temporal lobe tissue levels of S100 beta were shown by ELISA to be fivefold higher in 21 epileptics than in 12 controls (p < 0.001). The expression of the astrocyte intermediate filament protein, glial fibrillary acidic protein, was not significantly elevated in epileptics, suggesting a selective up regulation of S100 beta expression. Our findings, together with established functions of S100 beta, suggest that this neurotrophic cytokine may be involved in the pathophysiology of epilepsy. PMID- 7790866 TI - Glucose regulates glutamate-evoked arachidonic acid release from cultured striatal neurons. AB - L-Glutamate stimulates the liberation of arachidonic acid from mouse striatal neurons via the activation of N-methyl-D-aspartic acid (NMDA) receptors and by the joint stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and metabotropic receptors. In this study, we investigated whether starving cultured mouse striatal neurons of glucose would modify glutamatergic receptor-mediated arachidonic acid release. Glucose deprivation for 30 min led to enhancement of the NMDA-evoked release of arachidonic acid, compared with that observed in the presence of glucose. This enhanced response depended on both the concentration of glucose and the length of time of glucose deprivation. The enhanced NMDA response appeared to result from both a release of glutamate and the subsequent additional release of arachidonic acid due to the activation of AMPA and metabotropic receptors. Indeed, the increased NMDA response was completely reversed when extracellular glutamate was enzymatically removed. Moreover, glucose deprivation potentiated the combined AMPA/metabotropic receptor evoked release of arachidonic acid, even in the absence of extracellular glutamate. However, removing glucose did not improve the calcium rise induced by AMPA or NMDA. The ATP-evoked release of arachidonic acid from striatal astrocytes was not altered by glucose starvation. In summary, glucose deprivation affected two properties of striatal neurons: (a) it induced an NMDA-evoked release of glutamate from striatal neurons and (b) it selectively potentiated the AMPA/(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-evoked release of [3H]arachidonic acid without altering the authentic NMDA-mediated response. PMID- 7790865 TI - The 3' flanking region of the human tyrosine hydroxylase gene directs reporter gene expression in peripheral neuroendocrine tissues. AB - Cell type-specific expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), appears to be mediated in part by cis-acting elements located at the 3' end of the human gene. Further delineation of this region indicated sequences corresponding to a CACGTG motif significantly stimulated transcription of a heterologous promoter in various cell types. Mutation of this site led to a complete loss of activity. DNase footprinting, gel retardation, and UV cross linking experiments indicated that a 74-kDa cellular factor(s) bound specifically to the CACGTG motif in the pheochromocytoma cell line PC12. The size of this protein and its pattern of expression are compatible with those of the CACGTG binding protein TFE3. Transgenic animals were created using a 261-bp human TH 3' fragment encompassing the CACGTG motif in front of a thymidine kinase promoter/chloramphenicol acetyltransferase reporter gene. In three lines of mice this fragment was sufficient to direct a pattern of mRNA expression in peripheral neuroendocrine tissues that mimicked TH mRNA distribution. However, these sequences were not sufficient for CNS-specific patterns of expression. Thus, multiple cell type-specific enhancers may regulate TH gene expression in the CNS and periphery. PMID- 7790868 TI - Influence of perfusate glucose concentration on dialysate lactate, pyruvate, aspartate, and glutamate levels under basal and hypoxic conditions: a microdialysis study in rat brain. AB - The aim of this study was to evaluate the influence of perfusion media with different glucose concentrations on dialysate levels of lactate, pyruvate, aspartate (Asp), and glutamate (Glu) under basal and hypoxic conditions in rat brain neocortex. Intracerebral microdialysis was performed with the rat under general anesthesia using bilateral probes (o.d. 0.3 mm; membrane length, 2 mm) perfused with artificial CSF containing 0.0 and 3.0 mM glucose, respectively. Basal dialysate levels were obtained 2 h after probe implantation in artificially ventilated animals. Dialysate levels of glucose were also measured for the two different perfusion fluids. The mean absolute extracellular concentration of glucose was estimated by a modification of the no-net-flux method to be 3.3 mmol/L, corresponding to an average in vivo recovery of 6% for glucose. Hypoxia was induced by lowering the inspired oxygen concentration to 3%. Hypoxia caused a disturbance of cortical electrical activity, evidenced by slower frequency and lower amplitudes on the electroencephalogram compared with prehypoxic conditions. This was associated with significant elevations of lactate, Asp, and Glu levels. There were no statistically significant difference in dialysate metabolite levels between the two perfusion fluids, during either normal or hypoxic conditions. We conclude that microdialysis with glucose-free perfusion fluid does not drain brain extracellular glucose in anesthetized rats to the extent that the dialysate lactate, pyruvate, Asp, and Glu levels during basal or hypoxic conditions are altered. PMID- 7790869 TI - Effect of development of habituation to restraint stress on hypothalamic noradrenaline release and adrenocorticotropin secretion. AB - The effect of repeated stress has been studied on noradrenaline release in the hypothalamic paraventricular nucleus and on adrenocorticotropin levels. Rats were stressed by 20-min immobilization once a day for 5 days. On day 6 they were exposed to the same stress or to a different one (ether vapors for 2 min). Immobilization and ether stress increased noradrenaline release in naive rats (271 +/- 43 and 197 +/- 9%, respectively) and raised adrenocorticotropin levels, showing activation of the hypothalamus-pituitary axis. Repeated daily restraint did not modify basal noradrenaline or adrenocorticotropin levels. The further immobilization session on day 6 did not change noradrenaline levels at any observation time (20-120 min). The adrenocorticotropin response was still present, although significantly reduced. In repeatedly restrained rats, exposure to ether vapors induced a maximal increase in noradrenaline level similar to that observed in naive rats, although prolonged. In these rats the adrenocorticotropin response did not differ from that in acutely stressed rats. These results suggest that habituation may develop to a stressful stimulus leading to suppression of the hypothalamic noradrenergic response and that this phenomenon is stress specific. Moreover, modifications of noradrenaline release in the paraventricular nucleus are not solely responsible for the adrenocorticotropin response during stress, suggesting that other pathways and/or neurotransmitters are involved too. PMID- 7790867 TI - Effect of acute fluoxetine treatment on the brain serotonin synthesis as measured by the alpha-methyl-L-tryptophan autoradiographic method. AB - The effect of treatment with acute fluoxetine, a serotonin reuptake inhibitor, on the rate of serotonin synthesis in the rat brain was studied through autoradiography following intravenous administration of alpha-methyl-L [3H]tryptophan. The rate of serotonin synthesis in fluoxetine-treated rats was compared with the rate measured in sham-treated rats (saline injection). Results showed a significant increase in the rate of synthesis in the majority of cerebral structures examined. The greatest increase (given as a percentage of rates in control animals) in the rate of serotonin synthesis was observed in the substantia nigra compacta (344%), hippocampus-CA3 (337%), dorsal hippocampus (283%), and caudate-putamen (232%). Fluoxetine had a less significant effect on the rate of synthesis in the pineal body (44%). Data suggest that acute fluoxetine treatment (30 mg/kg, i.p.) enhances the rate of serotonin synthesis in all the structures of rat brain examined in this work. PMID- 7790870 TI - Effect of acute stress on hippocampal glutamate levels and spectrin proteolysis in young and aged rats. AB - Aging in rats is associated with a loss of hippocampal neurons, which may contribute to age-related cognitive deficits. Several lines of evidence suggest that stress and glucocorticoids may contribute to age-related declines in hippocampal neuronal number. Excitatory amino acids (EAAs) have been implicated in the glucocorticoid endangerment and stress-induced morphological changes of hippocampal neurons of young rats. Previously, we have reported that acute immobilization stress can increase extracellular concentrations of the endogenous excitatory amino acid, glutamate, in the hippocampus. The present study examined the effect of an acute bout of immobilization stress on glutamate levels in the hippocampus and medial prefrontal cortex of young (3-4-month) and aged (22-24 month) Fischer 344 rats. In addition, the effect of stress on spectrin proteolysis in these two brain regions was also examined. Spectrin is a cytoskeleton protein that contributes to neuronal integrity and proteolysis of this protein has been proposed as an important component of EAA-induced neuronal death. There was no difference in basal glutamate levels between young and old rats in the hippocampus or medial prefrontal cortex. During the period of restraint stress a modest increase in glutamate levels in the hippocampus of young and aged rats was observed. After the termination of the stress procedure, hippocampal glutamate concentrations continued to rise in the aged rats, reaching a level approximately five times higher than the young rats, and remained elevated for at least 2 h after termination of the stress. A similar pattern was also observed in the medial prefrontal cortex with an augmented post-stress induced glutamate response observed in the aged rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790871 TI - Investigation into the role of N-acetylaspartate in cerebral osmoregulation. AB - Marked abnormalities of the magnetic resonance intensity of N-acetylaspartate (NAA) have been reported in patients with various neurological disorders, but the neurochemical consequences of these alterations are difficult to assess because the function of NAA remains speculative. The purpose of this study was to examine whether NAA plays a role in protecting neurons against osmotic stress. Intracerebral microdialysis was used to expose a small region of the rat dorsolateral striatum to an increasingly hyposmotic environment and to measure resulting changes in NAA extracellular concentrations. NAA changes in the extracellular fluid (ECF) were compared with those of the amino acids, in particular, taurine, known to be involved in brain osmoregulation. Stepped increases in cellular hydration produced by hyposmotic perfusion media induced a marked increase in ECF NAA, reflecting a redistribution of NAA from intra-to extracellular space. Parallel experiments showed that, of all the extracellular amino acids measured, only taurine markedly increased with hyposmolar perfusion medium, indicating that the ECF NAA increase associated with hyposmotic stress was a specific response and not passive leakage out of the cells. As NAA is predominantly neuronal, it may contribute to the protection of neurons against swelling (i.e., regulatory volume decrease). In conditions with impaired blood brain barrier and cytotoxic oedema, efflux of intracellular NAA subsequent to sustained cellular swelling might lead to a reduction in total brain NAA detectable by magnetic resonance spectroscopy. Alternatively, redistribution of NAA from intra-to extracellular space implies changes in its chemical environment that may alter its magnetic resonance visibility. PMID- 7790872 TI - Direct detection of ascorbyl radical in experimental brain injury: microdialysis and an electron spin resonance spectroscopic study. AB - To examine the role played by free radicals in brain injury, we performed experiments to detect radicals in the frontal cortex of rats, using electron spin resonance (ESR) and microdialysis. A dialysis probe was inserted into the frontal cortex, and spin adducts in perfusates were immediately detected by ESR. We obtained a relatively stable doublet signal, with parameters of g = 2.0057 and aH = 0.17 mT. This signal corresponded with that of the ascorbyl radical. Ascorbyl radical in the perfusate collected from the frontal cortex was augmented by microinjection of H2O2 and FeCl2 adjacent to the dialysis probe. When the rats were challenged with cold-induced brain injury, ascorbyl radical and lactate dehydrogenase (LDH) level in the perfusate increased significantly. Pretreatment with superoxide dismutase and catalase attenuated the increase in ascorbyl radical and LDH level induced by the cold injury. Infusion of FeCl2 dissolved in perfusate caused a pronounced increase in ascorbyl radical and LDH level after the cold injury. We conclude that the direct detection of free radical formation further supports the hypothesis that free radicals play an important role in traumatic brain injury. Our findings also indicate that combined microdialysis with ESR spectroscopy is a useful in vivo method for monitoring free radical production in the brain. PMID- 7790875 TI - Resiniferatoxin-amide and analogues as ligands for protein kinase C and vanilloid receptors and determination of their biological activities as vanilloids. AB - The naturally occurring diterpene resiniferatoxin (RTX) is an ultrapotent analogue of capsaicin. Acting on polymodal afferent neurons, RTX induces a generally similar pattern of responses as does capsaicin. However, the two compounds, as well as other vanilloid derivatives, display different relative potencies for different responses. In the present study, we examined the vanilloid-like activities of two new derivatives, the amide analogue of RTX and phorbol 12,13-dibenzoate 20-homovanillylamide. Structurally, RTX-amide resembles capsaicin more closely than does RTX, and after cleavage of the amide bond the resulting amine would be predicted to not bind to protein kinase C in contrast to resiniferonol 9,13,14-orthophenylacetate, the parent diterpene of RTX. In contrast to our expectations the binding potency of the RTX-amide for the vanilloid receptor present in rat spinal cord was 450-fold lower than that of RTX (Ki values for the RTX-amide and RTX were 10.4 +/- 0.7 nM and 23.1 +/- 3.2 pM, respectively). In the case of phorbol 12,13-dibenzoate 20-homovanillylamide, there was a further loss of affinity for the vanilloid receptor compared with RTX; nonetheless, the Ki (8.56 +/- 0.61 microM) was comparable with that of capsaicin (5.31 +/- 0.37 microM). Computer fitting of the binding data yielded Hill coefficient values of 2.25 +/- 0.03, 2.33 +/- 0.03, and 1.84 +/- 0.05 for RTX, RTX-amide, and phorbol 12,13-dibenzoate 20-homovanillylamide, respectively, indicating that both new compounds induced apparent positive cooperativity among vanilloid binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790874 TI - Apoptotic cell death induced by beta-amyloid 1-42 peptide is cell type dependent. AB - beta-Amyloid peptide (A beta), a proteolytic fragment of the beta-amyloid precursor protein, is a major component of senile plaques in the brain of Alzheimer's disease patients. This neuropathological feature is accompanied by increased neuronal cell loss in the brain and there is evidence that A beta is directly neurotoxic. In the present study reduced cell viability in four different neuroblastoma cell types was observed after treatment with human A beta 1-42 for 1 day. Of the cell types tested rat PC12 and human IMR32 cells were most susceptible to A beta toxicity. Chromosomal condensation and fragmentation of nuclei were seen in PC12, NB2a, and B104 cells but not in IMR32 cells irrespective of their high sensitivity to A beta. Electrophoretic analysis of cellular DNA confirmed internucleosomal DNA fragmentation typical for apoptosis in all cell types except IMR32. These findings suggest that the form of A beta induced cell death (necrosis or apoptosis) may depend on the cell type. PMID- 7790873 TI - Antioxidant defense systems in the brains of type II diabetic mice. AB - The specific activities of superoxide dismutase, catalase, and glutathione S transferase (mu subtype) were significantly lower in the brains of mice with type II diabetes than in the brains of control mice. On the other hand, the specific activity of glutathione peroxidase was unaltered. The concentration of vitamin E, but not that of total glutathione and ascorbate, was increased in the brains of the type II diabetic mice. The relative amount of polyunsaturated fatty acids (as determined with soybean lipoxygenase) was increased in whole brains and crude synaptosomal membranes of the type II diabetic mice. Endogenous levels of thiobarbituric acid-positive material were decreased in both whole brain homogenates and crude synaptosomal membranes of the db/db mice. Susceptibility of lipids within whole brain homogenates and crude synaptosomal membranes of mice with type II diabetes to peroxidation with iron/ascorbate was also markedly decreased compared with that of controls. Vitamin E is known to quench lipid peroxidation. Therefore, decreased lipid peroxidation in the type II mouse brain may be due to increased vitamin E content. PMID- 7790876 TI - Characterization of cDNA and genomic clones encoding human myelin oligodendrocyte glycoprotein. AB - Myelin oligodendrocyte glycoprotein (MOG) is a transmembrane protein expressed only in the CNS and is a possible target autoantigen in multiple sclerosis (MS). To further study the association of MOG with MS, we have characterized cDNA and genomic clones encoding human MOG. The human MOG cDNA, like its rodent and bovine counterparts, encodes a mature protein containing an Ig-like domain, followed by two potential membrane-spanning regions. The intron-exon boundaries of the human MOG gene were mapped and revealed that the signal peptide is encoded by the first exon, the Ig-like domain of MOG is encoded on the second exon, whereas the remainder of the molecule is encoded by six shorter exons. In addition to the major cDNA species, a second class of MOG cDNA was isolated in which an intron was retained. Not only did this second cDNA species represent 30% of the clones analyzed (nine of 30), but RNA encoding this form was detectable by northern and reverse transcription-polymerase chain reaction analysis of the brain and spinal cord. Furthermore, we describe several restriction fragment length polymorphisms of the human MOG gene, one of which may be associated with MS susceptibility. PMID- 7790877 TI - Immunocytochemical analysis of axonal outgrowth in synaptotagmin mutations. AB - Synaptotagmin is a synaptic vesicle specific protein that binds calcium and phospholipids in vitro and is required for calcium-regulated fusion of synaptic vesicles with the presynaptic membrane. We have examined the possible requirement for synaptotagmin in axonal outgrowth by following neuronal development in Drosophila embryos deficient for the synaptotagmin gene. We find that synaptotagmin is expressed abundantly in axons and growth cones before synapse formation in wild-type embryos. Using antibodies to the intravesicular domain of synaptotagmin to label live embryos, we demonstrate that vesicle populations containing synaptotagmin actively undergo exocytosis during axonogenesis. We have used immunocytochemical techniques to examine the distribution of the axonal protein Fasciclin II, the presynaptic membrane protein syntaxin, and the synaptic vesicle protein cysteine string protein, in synaptotagmin null mutations. The distribution of these proteins is similar in wild-type and synaptotagmin mutant embryos, suggesting that synaptotagmin is not required for axonogenesis in the CNS or PNS. Based on these findings, we suggest that the molecular mechanisms underlying vesicular-mediated membrane expansion during axonal outgrowth are distinct from those required for synaptic vesicle fusion during neurotransmitter release. PMID- 7790878 TI - Effect of protein kinase C modulators on 14,15-epoxyeicosatrienoic acid incorporation into astroglial phospholipids. AB - Our previous studies have shown that 14,15-epoxyeicosatrienoic acid (14,15-EET) is a major product of arachidonic acid metabolism in astrocytes. The purpose of this study was to investigate cellular regulation of 14,15-EET incorporation, distribution, and metabolism in primary cultures of rat brain cortical astrocytes. Incorporation of 14,15-EET into astrocytes was lower (93,390 +/- 11,121 dpm/5 x 10(6) cells) than incorporation of 8,9-EET (226,500 +/- 5,567 dpm/5 x 10(6) cells) and arachidonic acid (321,600 +/- 1,200 dpm/5 x 10(6) cells). 14,15-EET was distributed in the order neutral lipids and free fatty acids (solvent front) >> phosphatidylcholine (PC) > phosphatidylinositol (PI) > phosphatidylethanolamine. In contrast, 8,9-EET and arachidonic acid were exclusively incorporated into PC. During incubation, astroglial epoxide hydrolase selectively metabolized 14,15-EET, but not 8,9-EET, to its vic-diol. Although 4 phenylchalcone oxide, a potent inhibitor of epoxide hydrolase, completely inhibited 14,15-EET metabolism, a large amount of cell-incorporated radioactivity remained as free 14,15-EET. Long-term exposure of astrocytes to 4 beta-phorbol 12 myristate 13-acetate (4 beta-PMA) resulted in a time-dependent incorporation of 14,15-EET into PI but not in control cells exposed to 4 alpha-phorbol 12,13 didecanoate. PKC down-regulation completely inhibited epoxide hydrolase metabolism of 14,15-EET. Following recovery of down-regulated PKC, 1 week after treatment with 4 beta-PMA, astrocytes regained their normal pattern of low incorporation of 14,15-EET. Protein kinase C (PKC) inhibition by staurosporine enhanced 14,15-EET incorporation without affecting its metabolism to 14,15 dihydroxyeicosatrienoic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790879 TI - GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. AB - The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction. PMID- 7790880 TI - Repeated administration of gamma-vinylGABA reduces rat brain glutamine synthetase activity. AB - The glutamine cycle has been proposed as a pathway in which glutamine synthesized in glia provides substrate for synthesis of the neurotransmitters glutamate and GABA as they are lost from neurons. To test whether GABA may regulate this pathway, the effect of elevated GABA on the glial enzyme glutamine synthetase was examined in rat brain. Repeated subcutaneous injections of the antiepileptic GABA transaminase inhibitor gamma-vinylGABA at a dose of 150 mg/kg per day for 21 days reduced glutamine synthetase activity by 36% in the cortex and 22% in the cerebellum. At 30 mg/kg per day, glutamine synthetase activity was reduced by 9.5% in the cortex but unchanged in the cerebellum. The reductions were brain specific because the skeletal muscle and liver enzymes were unaffected by gamma vinylGABA administration. Amino acid analysis of the cortex from gamma-vinylGABA treated rats demonstrated a 270% increase in GABA levels after 150 mg/kg but no change after 30 mg/kg. GABA levels and glutamine synthetase activity were inversely correlated. The 150 mg/kg dose significantly lowered cortical glutamine and glutamate levels. The decline in brain glutamine synthetase activity with chronic gamma-vinylGABA administration developed gradually over time and may be due to the slow turnover of this enzyme in vivo. PMID- 7790882 TI - Iron regulation in the developing rat brain: effect of in utero ethanol exposure. AB - Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brainstem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron dependent growth processes such as myelination. PMID- 7790881 TI - Stimulation of cyclic GMP production via a nitrosyl factor in sensory neuronal cultures by algesic or inflammatory agents. AB - Capsaicin stimulates cyclic GMP production via nitric oxide (NO) (or another nitrosyl factor) in dorsal root ganglion (DRG) neurons maintained in culture. The purpose of the present study was to characterize further capsaicin stimulation of cyclic GMP production in DRG cells maintained in culture, investigate other algesic and/or inflammatory agents for effects on cyclic GMP production, and examine cells responsible for NO production and cyclic GMP production. Capsaicin stimulation of cyclic GMP production in DRG cells was dose dependent, receptor mediated, and attenuated by hemoglobin. Prostaglandin E2, substance P, and calcitonin gene-related peptide did not affect basal, capsaicin-stimulated, or bradykinin-stimulated cyclic GMP production. Other inflammatory or algesic agents, including serotonin, histamine, ATP, glutamate, aspartate, and NMDA, did not affect cyclic GMP production. Pretreatment of DRG cells with lipopolysaccharide increased basal cyclic GMP production in neuronal but not in nonneuronal cultures and facilitated stimulation of cyclic GMP production by L arginine. Capsaicin pretreatment of neuronal DRG cultures, which destroys capsaicin-sensitive (small diameter) afferent neurons, attenuated capsaicin- and bradykinin-stimulated cyclic GMP production but did not affect basal or sodium nitroprusside-stimulated cyclic GMP production. These results indicate that capsaicin elicits production of a nitrosyl factor via capsaicin-sensitive (small diameter) neurons. Capsaicin evoked cyclic GMP production in nonneuronal DRG cultures in the presence but not in the absence of apposed neuronal DRG cultures. Overall, these findings suggest that specific exogenous (or endogenous) substances may stimulate production of a nitrosyl factor(s) by a subset of DRG neurons, and nitrosyl factors produced by these neurons may affect cyclic GMP production in neighboring neuronal or non-neuronal cells. PMID- 7790883 TI - Distribution of calretinin, calbindin D28k, and parvalbumin in subcellular fractions of rat cerebellum: effects of calcium. AB - The distribution of calretinin, calbindin D28k, and parvalbumin was examined in subcellular fractions prepared from rat cerebellum and analyzed by immunoblot. Calretinin was also quantified by radioimmunoassay. As expected, all three soluble, EF-hand calcium-binding proteins were predominantly localized in the cytosolic fraction. Calretinin and calbindin D28k were also detected in membrane fractions. Calretinin was more abundant in synaptic membrane than in microsomal fractions. The cerebellar microsomal fraction contained the greatest concentration of membrane-associated calbindin D28k. The association of calretinin and calbindin D28k with membrane fractions was decreased in samples prepared or incubated in low calcium. Quantification of calretinin in subcellular fractions of rat cerebellum revealed a greater amount of calretinin in cytosolic fractions prepared or incubated in low calcium and reduced amounts of calretinin in all membrane fractions incubated in low calcium with the exception of the mitochondrial fraction. These results imply that calretinin and calbindin D28k might have physiological target molecules that are associated with, or are components of, brain membranes. PMID- 7790884 TI - Degradation of dynorphin-related peptides by the puromycin-sensitive aminopeptidase and aminopeptidase M. AB - The degradation of dynorphin-related peptides by the puromycin-sensitive aminopeptidase and aminopeptidase M was examined using these peptides as alternate substrate inhibitors. Ki determinations showed that both aminopeptidases exhibit a higher affinity for longer dynorphin-related peptides, i.e., Ki for dynorphin A-17 = 23-30 nM with the Ki increasing to 25-50 microM for the enkephalin pentapeptides. Binding appears dependent not only on peptide length, but also on its sequence. With aminopeptidase M, as the peptide size increases from five to 10 amino acids, kcat remains relatively constant; however, as the peptide size increases beyond a decapeptide, kcat decreases significantly. With the puromycin-sensitive aminopeptidase, similar results were obtained except that kcat was greatest for the pentapeptide. Thus, if one considers kcat/Km as the relevant kinetic constant for estimating in vivo peptide hydrolysis, these results are consistent with the involvement of aminopeptidase M and the puromycin sensitive aminopeptidase in the degradation of extended dynorphin-related peptides. PMID- 7790885 TI - Rapid dephosphorylation of tau in heat-shocked fetal rat cerebral explants: prevention and hyperphosphorylation by inhibitors of protein phosphatases PP1 and PP2A. AB - We heat shocked 21- and 35-day-old fetal rat cerebral explants at 45 degrees C for 18 min and performed immunocytochemistry and immunoblot analysis of sodium dodecyl sulfate extracts using the monoclonal anti-tau antibodies Tau-1, Tau-5, Tau-46, and PHF-1 and the peroxidase-antiperoxidase technique or 125I-labeled protein A. Tau-1 and PHF-1 recognize nonphosphorylated and phosphorylated epitopes, respectively, and both Tau-5 and Tau-46 recognize phosphate-independent epitopes. tau immunoreactivity was confined to neurons and increased in heat shocked perikarya but not axons. At 0 h after heat shocking, there was dephosphorylation of tau exemplified by (1) faster migration of tau isoforms with resultant loss or attenuation of the 60- and 52-kDa tau isoforms recognized by all four anti-tau antibodies and concomitant accentuation of the fastest moving 50-kDa tau isoform recognized by Tau-1, Tau-5, and Tau-46; and (2) significant increase in the nonphosphorylated Tau-1 epitope with resultant decreases in the ratio of total (phosphorylated plus nonphosphorylated) tau to nonphosphorylated tau and the difference of total tau minus nonphosphorylated tau. tau was phosphorylated back to the control level by 12 h and remained so at 24 and 48 h after heat shocking. Treatment of explants with cycloheximide, a protein synthesis inhibitor, did not prevent the heat shocking-induced dephosphorylation of tau. Treatment of explants with the inhibitors of protein phosphatases PP1 and PP2A, okadaic acid or calyculin A, produced hyperphosphorylated tau polypeptides, prevented the heat shocking-induced dephosphorylation of tau, and intensified the immunoreactivity of the neurofilament subunit H with the only antiphosphoneurofilament antibody that reacts with intraneuronal neurofibrillary tangles. In 35-day-old explants, in addition to the three 50-, 52-, and 60-kDa tau isoforms seen in 21-day-old explants, a 66-kDa tau polypeptide was also present. PMID- 7790886 TI - Internalization of voltage-dependent sodium channels in fetal rat brain neurons: a study of the regulation of endocytosis. AB - In fetal rat brain neurons, activation of voltage-dependent Na+ channels induced their own internalization, probably triggered by an increase in intracellular Na+ level. To investigate the role of phosphorylation in internalization, neurons were exposed to either activators or inhibitors of cyclic AMP- and cyclic GMP dependent protein kinases, protein kinase C, and tyrosine kinase. None of the tested compounds mimicked or inhibited the effect of Na+ channel activation. An increase in intracellular Ca2+ concentration induced either by thapsigargin, a Ca(2+)-ATPase blocker, or by A23187, a Ca2+ ionophore, was unable to provoke Na+ channel internalization. However, Ca2+ seems to be necessary because both neurotoxin- and amphotericin B-induced Na+ channel internalizations were partially inhibited by BAPTA-AM. The selective inhibitor of Ca2+/calmodulin dependent protein kinase II, KN-62, caused a dose-dependent inhibition of neurotoxin-induced internalization due to a blockade of channel activity but did not prevent amphotericin B-induced internalization. The rate of increase in Na+ channel density at the neuronal cell surface was similar before and after channel internalization, suggesting that recycling of internalized Na+ channels back to the cell surface was almost negligible. Pretreatment of the cells with an acidotropic agent such as chloroquine prevented Na+ channel internalization, indicating that an acidic endosomal/lysosomal compartment is involved in Na+ channel internalization in neurons. PMID- 7790887 TI - Ascorbate transport and intracellular concentration in cerebral astrocytes. AB - Regulation of the initial rate of uptake and steady-state concentration of ascorbate (reduced vitamin C) was investigated in rat cerebral astrocytes. Although these cells did not synthesize vitamin C, they accumulated millimolar concentrations of ascorbate when incubated with medium containing the vitamin at a level (200 microM) typical of brain extracellular fluid. Initial rate of [14C] ascorbate uptake and intracellular ascorbate concentration were dependent on extracellular Na+ and sensitive to the anion transport inhibitor sulfinpyrazone. Comparison of the efflux profiles of ascorbate and 2',7'-bis(carboxyethyl)-5 (or 6)-carboxyfluorescein from astrocytes permeabilized with digitonin localized most intracellular ascorbate to the cytosol. Pretreatment of astrocytes with dibutyryl cyclic AMP (dBcAMP) doubled their initial rate of sulfinpyrazone-sensitive [14C]ascorbate uptake compared with cells treated with either n-butyric acid or vehicle. dBcAMP also increased steady-state intracellular ascorbate concentration by 39%. The relatively small size of the change in astrocytic ascorbate concentration was explained by the finding that dBcAMP increased the rate of efflux of the vitamin from ascorbate-loaded cells. These results indicate that uptake and efflux pathways are stimulated by cyclic AMP-dependent mechanisms and that they regulate the cytosolic concentration of ascorbate in astrocytes. PMID- 7790888 TI - Lack of effects of inhibition of nitric oxide synthesis on local glucose utilization in the rat brain. AB - The effects of chronic treatment with NG-nitro-L-arginine methyl ester, a potent inhibitor of nitric oxide synthase activity, on local cerebral glucose utilization were examined in conscious rats. Intraperitoneal injections of 50 mg/kg of the nitroarginine twice daily for 4 days have been found to result in almost complete inhibition of nitric oxide synthase activity in brain. Local cerebral glucose utilization was determined by means of the quantitative autoradiographic [14C]deoxyglucose method in an experimental group (n = 7) of rats that were treated with the nitroarginine according to this schedule and in a normal control group (n = 7) treated similarly with saline. The rats were conscious but partially restrained during the determinations of local cerebral glucose utilization. The nitroarginine treatment raised mean arterial blood pressure statistically significantly to 147 +/- 3 mm Hg (mean +/- SEM) from a level of 120 +/- 5 mm Hg in the saline controls (p < 0.001 by grouped t test), but there were no statistically significant effects on glucose utilization in any of 39 brain structures examined. It is concluded that nitric oxide normally exerts no significant influence on energy metabolism in the rat brain. PMID- 7790889 TI - Down-regulation of c-neu receptors by nerve growth factor in PC12 cells. AB - A small number of p185c-neu receptors have been found on PC12 cells. These receptors show some basal phosphorylation in quiescent cells. When the cells are treated with nerve growth factor (NGF) for a short time, some increase in phosphorylation is seen, mainly on serine and threonine residues, and this is accompanied by a slight shift in the apparent molecular weight. Epidermal growth factor (EGF) also increases the phosphorylation of p185c-neu, in this case on tyrosine residues. Neither heregulin-beta 1 nor gp30 stimulates the tyrosine phosphorylation of p185c-neu, and neither has a proliferative effect on the cells. Treatment of the cells with NGF for 5 days produces a 70-80% reduction in the number of p185c-neu receptors. This down-regulation does not occur when PC12nnr5 cells, which lack the high-affinity NGF receptor, p140trk, are treated with NGF. The level of p185c-neu mRNA is not altered by NGF treatment, suggesting that the down-regulation is due to either a translational or a posttranslational alteration. PMID- 7790891 TI - Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration. AB - We compared the activity of free D-Ser on the potentiation of cloned NMDA receptors with that of Gly by using a Xenopus oocyte expression system. The extracellular concentration of free D-Ser and Gly was further studied by means of microdialysis. The ED50 values of D-Ser were three to four times lower than those of Gly in any combination of epsilon 1, epsilon 2, epsilon 3, or epsilon 4 and zeta 1. Site-directed mutagenesis of zeta 1 subunits revealed that some aromatic residues necessary for the action of Gly affected the ED50 value of D-Ser. This result showed that the residues play crucial roles in the action of D-Ser. In vivo microdialysis of rodent brain revealed that the extracellular concentration of free D-Ser in the frontal cortex (6.5 microM) was high enough to saturate the Gly site on the NMDA receptor, but that in the cerebellum was not. These findings suggest that D-Ser is a candidate of the endogenous potentiator of the NMDA receptor in the rodent frontal cortex. PMID- 7790890 TI - Processing of procarboxypeptidase E into carboxypeptidase E occurs in secretory vesicles. AB - Carboxypeptidase E (CPE) functions in the posttranslational processing of bioactive peptides. Like other peptide processing enzymes, CPE is initially produced as a precursor ("proCPE") that undergoes posttranslational processing at a site containing five adjacent Arg residues near the N-terminus and at other sites near the C-terminus of proCPE. The time course of the N-terminal processing step suggests that this conversion occurs in either the Golgi apparatus or the secretory vesicles. To delineate further the site of proCPE processing, pulse/chase analysis was performed under conditions that block transit out of the Golgi apparatus (brefeldin A, carbonyl cyanide m-chlorophenylhydrazone, or 20 degrees C) or that block acidification of vesicles (chloroquine, monensin, or ammonium chloride). The results of these analysis suggest that efficient proCPE processing requires an acidic post-Golgi compartment. To test whether known processing enzymes can perform this cleavage, purified proCPE was incubated with furin, prohormone convertase 1, or a dynorphin converting enzyme, and the products were analyzed on denaturing polyacrylamide gels. Furin cleaves proCPE within the N-terminal region, although the reaction is not very efficient, requiring relatively large amounts of furin or long incubation times. The other two peptide processing enzymes did not cleave proCPE, whereas a relatively small amount of secretory granule extract was able to convert proCPE into CPE. Taken together, these findings suggest that the conversion of proCPE into CPE occurs primarily in secretory vesicles. PMID- 7790892 TI - Expression of protein kinase C family members in the cerebral endothelial cells. AB - The protein kinase C (PKC) family is composed of at least four conventional (alpha, beta I, beta II, and gamma) and several related novel (delta, epsilon, eta, and zeta) isoforms with different distribution and sensitivity to Ca2+ and phorbol esters. The enzyme is known to be present in cerebral endothelial cells. We have investigated the occurrence of seven isoforms (alpha, beta, gamma, delta, epsilon, eta, and zeta) by using reverse transcriptase-polymerase chain reaction in rat brain, in a freshly isolated brain microvessel fraction, in primary cultures of rat brain endothelial cells, in an immortalized rat brain endothelial cell line, and in aortic endothelial cell cultures. Brain tissue contained all seven investigated isoforms. A similar expression pattern was seen in freshly purified microvessels, but the PKC-gamma isoform could not be detected. Primary cultures of endothelial cells expressed PKC-alpha, -beta, -delta, -eta, and epsilon isoenzymes, whereas the immortalized cell line expressed PKC-alpha, delta, -epsilon, and -eta. The rat aortic endothelium contained only PKC-alpha and -delta isoforms. The variety of expression patterns of PKC family members in endothelial cells of different type may reflect differences in the functional responsiveness to environmental stimuli. Because PKC has been shown to be involved in the regulation of the blood-brain barrier permeability, the presence of different isoforms may confer a sophisticated intracellular regulatory mechanism to the brain endothelial cells. PMID- 7790893 TI - Ceramide prevents neuronal programmed cell death induced by nerve growth factor deprivation. AB - We examined the ability of ceramide and sphingomyelinase (SMase) to prevent neuronal programmed cell death (PCD). We found that a cell-permeable ceramide analogue prevented neuronal PCD when applied to established sympathetic neuron primary cultures at the time of nerve growth factor (NGF) deprivation. Other amphiphilic lipids such as oleic acid failed to prevent cell death. Exogenous SMase also showed the same effect, probably by raising the intracellular ceramide level by sphingomyelin (SM) breakdown. Phosphocholine, another hydrolytic product of SM by SMase, did not prevent cell death. Other phospholipases, such as phospholipase C and phospholipase A2, could not prevent cell death. Given the recent findings that the SM cycle is activated to increase the intracellular ceramide level on NGF binding to the low-affinity NGF receptor (LNGFR) and that NGF binding to LNGFR suppresses apoptosis in neuronal cell lines, our results suggest the possibility of the SM cycle as a signaling mechanism transducing the PCD-preventing activity of NGF. PMID- 7790894 TI - Pentylenetetrazole-induced seizure up-regulates levels of microtubule-associated protein 1B mRNA and protein in the hippocampus of the rat. AB - Stimuli that evoke seizure are capable of inducing structural changes in the hippocampus. However, late-acting genes related to these changes have not been described. Administration of pentylenetetrazole (PTZ; 50 mg/kg) to rats of various ages evoked tonic-clonic seizures. Using RNA gel blot analysis we found that the level of the mRNA for microtubule-associated protein 1B (MAP1B) was robustly increased in the hippocampus of 3-month-old rats. The levels of MAP1B mRNA in hippocampus peaked at 40 h and began to decline by 72 h following PTZ treatment. Immunoblotting with anti-MAP1B antibody demonstrates the increase in content of immunoreactive proteins 40-72 h after seizure onset in the hippocampus of PTZ-treated rats. These results indicate that MAP1B is a sensitive indicator of hippocampal structural changes occurring in response to PTZ-induced seizure activity. PMID- 7790896 TI - Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina. AB - Evidence from in vitro studies suggests that excitotoxic neuronal degeneration can occur by either an acute or delayed mechanism. Studies of the acute mechanism in isolated chick embryo retina using histological methods indicate that this process is rapidly triggered by activation of glutamate receptors of either the N methyl-D-aspartate (NMDA) or non-NMDA subtypes. The delayed mechanism, studied primarily in cortical and hippocampal cell cultures prepared from embryonic rodent brain, requires activation of NMDA receptors. In these cell culture systems, stimulation of non-NMDA receptors does not rapidly trigger delayed neuronal degeneration, or does so only indirectly, via activation of NMDA receptors secondary to glutamate release. To provide a more valid basis for comparison of these two mechanisms, we have modified the isolated chick embryo retina model to permit studies of delayed as well as acute excitotoxic neurodegeneration. Retinas maintained for 24 h exhibited no morphological or biochemical signs of damage. Retinal damage was assessed by measuring lactate dehydrogenase (LDH) present in the medium at various times after exposure to agonists and normalized to total LDH in each retina. Glutamate exposure (1 mM, 30 min) did not result in LDH release by the end of the exposure period, but LDH was released over the following 24 h. Briefer periods also led to substantial LDH release. Incubation in the presence of NMDA, or the non-NMDA agonists kainate (KA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), led rapidly to delayed LDH release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790895 TI - All-trans- and 9-cis-retinoic acid enhance the cholinergic properties of a murine septal cell line: evidence that the effects are mediated by activation of retinoic acid receptor-alpha. AB - We investigated the effects of retinoids on the cholinergic properties of a murine septal cell line, SN56. Treatment of the cells with all-trans-retinol (vitamin A), all-trans-retinal, all-trans-retinoic acid (t-RA), 9-cis-retinoic acid (9c-RA), or 13-cis-retinoic acid caused time- and concentration-dependent increases in choline acetyltransferase activity (up to 3.4-fold) and in intracellular acetylcholine levels (up to 2.5-fold, with respective EC50 values of 68, 50, 18, 15, and 56 nM). Furthermore, treatment with either t-RA or 9c-RA at 1 microM for 48 h resulted in an increase in the expression of choline acetyltransferase mRNA by threefold that of controls. These data and the presence of putative retinoic acid response elements in the 5' region of the murine choline acetyltransferase gene indicate that retinoids stimulate choline acetyltransferase transcription in murine cholinergic neurons. No additivity or synergism was observed between the effects of t-RA and 9c-RA on any of these cholinergic properties of SN56 cells, suggesting a common mechanism of action of the two retinoids. However, a combined treatment with t-RA and forskolin, which activates adenylate cyclase, resulted in an additive increase in acetylcholine content. Using an antagonist selective for the retinoic acid receptor-alpha subtype, Ro 41-5253, we found that the effects of t-RA and 9c-RA on acetylcholine levels were abolished. An agonist selective for retinoic acid receptor-alpha, Ro 40-6055, increased acetylcholine levels to a similar extent as t-RA and 9c-RA, and this effect was blocked by the antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790897 TI - gamma-Hydroxybutyric acid increases intracellular Ca2+ concentration and nuclear cyclic AMP-responsive element- and activator protein 1 DNA-binding activities through GABAB receptor in cultured cerebellar granule cells. AB - In primary cultures of mouse cerebellar granule cells, a brief stimulation by gamma-hydroxybutyric acid (GHB, 0.1-3 mM) significantly increased the intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In addition, gel mobility assay showed that exposure of the cells to GHB also increased nuclear DNA-binding activity specific for the cyclic AMP-responsive element (CRE) and activator protein 1 (AP-1) transcriptional element in a concentration-dependent manner. The concentration range of GHB that increased the DNA-binding activity was essentially the same as the concentration range that elicited the increase in [Ca2+]i. The GHB-induced increases in [Ca2+]i and nuclear DNA-binding activity were antagonized by specific GABAB antagonists such as p-[3-aminopropyl]-p-diethoxymethylphosphinic acid (CGP 35 348) and 3-N-[1-(S) (3,4-dichlorobenzyl)ethanol-2-(S)-hydroxy-P-benzylphosphin ic acid (CGP 55 845). In addition, the GHB-induced increase in [Ca2+]i was abolished by pretreatment of the cells with islet-activating protein. Furthermore, treatment of the cells with 1,2-bis(2'-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM) and thapsigargin blocked the GHB-induced increase in nuclear DNA binding activity. GHB inhibited [3H]baclofen binding to cultured cerebellar granule cells and mouse cerebellar membranes. These results suggest that stimulation of GABAB receptors by GHB activates intracellular Ca2+ stores and that the increased [Ca2+]i resulting from release of stored Ca2+ plays an important role in increasing the CRE- and AP-1 DNA-binding activities in cultured cerebellar granule cells. PMID- 7790898 TI - L1 and N-CAM antibodies trigger protein phosphatase activity in growth cone enriched membranes. AB - Triggering of the cell adhesion molecules L1 or N-CAM in a nerve growth cone membrane fraction from fetal rat brain with purified L1 or N-CAM or specific antibodies decreases the steady-state levels of protein tyrosine phosphorylation in the membranes. Here we report that triggering of L1 and N-CAM in the growth cone-enriched membrane fraction with a subset of antibodies directed against the extracellular region of L1 and N-CAM elicited dephosphorylation of endogenous protein substrates, indicating the presence of a cell adhesion molecule-activated phosphatase. The most prominent substrates were a membrane-associated 200-kDa protein and tubulin, both of which were dephosphorylated on tyrosine and serine/threonine residues in response to L1 or N-CAM triggering. The antibody induced phosphatase was inhibited by agents that blocked tyrosine and serine/threonine phosphatases, including sodium orthovanadate, vanadyl sulfate, zinc cations, heparin, and sodium pyrophosphate. Purified L1 and N-CAM fragments and other antibodies reacting with the extracellular region of these adhesion molecules did not activate the phosphatase but did inhibit tyrosine phosphorylation. These properties suggested that triggering of L1 and N-CAM can lead to either phosphatase activation or tyrosine kinase inhibition in growth cone membranes. These findings implicate protein phosphatases in addition to tyrosine kinases as components of L1 and N-CAM intracellular signaling pathways in growth cones. PMID- 7790899 TI - Uptake of L-glutamate into rat brain synaptic vesicles: effect of inhibitors that bind specifically to the glutamate transporter. AB - In this study we have described a series of new and potent inhibitors of the vesicular uptake of glutamate. The two most efficient inhibitors were the dyes Evans blue and Chicago Skye Blue 6B, which are structurally related to glutamate and were competitive inhibitors in the nanomolar range. The anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (SITS) and the diuretics furosemide and bumetanide are inhibitors of chloride transport in other organs but were competitive inhibitors of glutamate and noncompetitive with respect to chloride ions. Evans blue, Chicago Skye Blue 6B, SITS, furosemide, and bumetanide are all large organic acids with two centers of negative charge and an electron donating group at close vicinity of the negative charge at physiological pH. The inhibition of the glutamate uptake with these inhibitors was noncompetitive with respect to Cl-. The inhibitors, therefore, probably interact directly with the glutamate carrier. Bafilomycin A1, which is a specific vacuolar ATPase inhibitor, was used as a control and inhibited the vesicular dopamine, glutamate, and GABA uptake to the same extent. None of the inhibitors had any effect on the plasma membrane carrier, which is therefore clearly different from the vesicular carrier. PMID- 7790900 TI - Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail. AB - We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia. PMID- 7790901 TI - Somatodendritic internalization and perinuclear targeting of neurotensin in the mammalian brain. AB - Polypeptide hormones and growth factors have long been known to internalize into peripheral target cells as a result of their interaction with cell surface receptors. Studies in culture have suggested that certain neuropeptides might undergo a similar type of translocation in neurons. To investigate this possibility in adult mammalian brain, we have examined by confocal laser microscopy the events that follow the binding of fluorescein-tagged derivatives of the tridecapeptide neurotensin to basal forebrain cholinergic cells. Our results demonstrate a selective time- and temperature-dependent internalization of fluo-neurotensin in these cells. This internalization is receptor mediated, proceeds from the entire somatodendritic membrane of the cells, and utilizes endosome-like organelles which are mobilized from dendrites to perikarya and from the periphery of the cell to its perinuclear region. Parallel studies carried out on Sf9 insect cells expressing the rat neurotensin receptor from a recombinant baculovirus indicated that the internalization process involves receptor-ligand complexes and not merely the fluorescent peptide itself. These data suggest that receptor internalization plays a role in neuropeptide signaling in the brain and that it can be harnessed for selective identification of neuropeptide target cells. PMID- 7790902 TI - The postsynaptic localization of the glycine receptor-associated protein gephyrin is regulated by the cytoskeleton. AB - The mechanisms underlying the postsynaptic localization of neurotransmitter receptors are poorly understood. Recently, the peripheral membrane protein gephyrin has been shown to be essential for the formation of inhibitory glycine receptor clusters in cultured rat spinal cord neurons. In vitro gephyrin binds with high affinity to polymerized tubulin. Here, the interaction of gephyrin with different components of the cytoskeleton was investigated in primary cultures of rat spinal neurons. After treatment with alkaloids affecting the cytoskeleton, the morphology of post-synaptic gephyrin clusters was analyzed by confocal immunofluorescence microscopy. Depolymerization of microtubules by demecolcine reduced both the percentage of cells with postsynaptic gephyrin clusters and the number of clusters/cell. The size of the remaining gephyrin clusters was increased whereas their gephyrin density was significantly lower than under control conditions. Depolymerization of microfilaments by cytochalasin D in contrast generated smaller clusters of increased gephyrin density. Demecolcine also dispersed postsynaptic glycine receptor clusters as revealed by immunostaining with a specific monoclonal antibody. These findings support the view that in vivo gephyrin anchors receptor polypeptides to the cytoskeleton by a complex interaction with microtubules and microfilaments. PMID- 7790903 TI - Changes in expression and distribution of Aplysia cell adhesion molecules can influence synapse formation and elimination in vitro. AB - 5-HT or FMRFamide evoke long-lasting changes in the efficacy of sensorimotor (SN L7) synapses of Aplysia, structural alterations of the presynaptic sensory cell, and cell-specific downregulation in the distribution of the adhesion molecule apCAM. We examined how the cell-specific changes in apCAM might contribute to the formation of new presynaptic varicosities by 5-HT or the elimination of existing presynaptic varicosities by FMRFamide. We report that the formation of new sensory varicosities is directed by the presence of preexisting zones on the motor axon that are enriched for apCAM. Moreover, there was a further enrichment of apCAM levels at existing sensory varicosities contacting the motor axon beginning at 1 hr and lasting 24 hr after treatment with 5-HT. As was found for synapse formation during the early stages of cell-cell interaction, incubation with anti-apCAM mAb blocked the 5-HT-induced long-term changes in synaptic efficacy and the accompanying changes in sensory neuron structure. Long-term synaptic depression with FMRFamide was accompanied by an overall decline of apCAM levels. Treatment with FMRFamide evoked an even greater decline in apCAM levels at sites of sensory varicosities that preceded the structural changes and persisted especially at sites where sensory varicosities are eliminated. These results suggest that neurotransmitters evoke both cell- and site-specific changes in the levels of adhesion molecules that can influence either the formation or the elimination of presynaptic varicosities that accompany long-term heterosynaptic modulation of a behaviorally relevant synaptic connection. PMID- 7790904 TI - Individual variation and lateral asymmetry of the rat primary somatosensory cortex. AB - We have evaluated the interindividual variability and lateral symmetry of a major cortical area by comparing the primary somatosensory cortex (S1) of adult rats. Our choice of the rat was dictated by the accuracy with which one can measure S1 and its component representations in the rodent brain; the importance of such measurements lies in understanding the rules that govern the allocation of cortical space and, ultimately, the consequences of differential allocation for behavior. With respect to interindividual differences, the major somatic representations in S1 are surprisingly variable in size. The area of the whiskerpad representation, for example, ranged from 3.72 to 6.84 mm2 in a sample of 53 rats; other components of S1 showed comparable differences among animals. With respect to lateral symmetry, the average area of each major representation was similar for the right and left hemispheres; thus, we found no consistent bias in the size of S1 or its elements in the sample as a whole. Within individual animals, however, the sizes of the major somatic representations were often quite different in the two hemispheres. The magnitude of the lateral differences averaged 7.9 +/- 0.8% (mean +/- SEM) for the whisker pad representation, 11.6 +/- 1.3% for the upper lip, 15.4 +/- 1.6% for the furry buccal pad, 13.9 +/- 1.4% for the lower jaw, and 13.3 +/- 1.2% for the forepaw. These results show that the amount of cortical space allocated to corresponding functions in individual rats- or in the two hemispheres of a particular rat--are often different. Such variations are likely to be reflected in somatosensory performance. PMID- 7790905 TI - Cytochrome-oxidase blobs in cat primary visual cortex. AB - Cytochrome-oxidase blobs are central to two of the most influential ideas in contemporary visual neuroscience--cortical modularity and parallel processing pathways. In particular, the regular 2D array of cytochrome-oxidase-rich blobs in primate visual cortex is arguably the most compelling evidence for cortical modularity and has been hypothesized to mark a separate processing stream through the visual cortex. Although previously a variety of mammals have been studied, blobs have only been demonstrated in the visual cortex of primates, which has led to the conclusion that blobs represent a primate-specific feature of visual cortical organization. Here we demonstrate the presence of cytochrome-oxidase blobs in a nonprimate species. Throughout the full tangential extent of layers II III in cat visual cortex the cytochrome-oxidase staining pattern is distinctly patchy, with the darkly stained blobs forming a regular 2D array. In addition, the blobs in cat visual cortex are functionally related to the underlying ocular dominance columns. The presence of cytochrome-oxidase blobs in the cat clearly demonstrates that they no longer can be considered a primate-specific feature of visual cortical organization. PMID- 7790906 TI - Synaptic differentiation of a single motor neuron: conjoint definition of transmitter release, presynaptic calcium signals, and ultrastructure. AB - The opener muscle in the walking legs of the crayfish (Procambarus clarkii) is innervated by only one excitatory motor neuron, yet excitatory postsynaptic potentials (EPSPs) of proximal fibers are eightfold larger than those of central muscle fibers at low frequencies of activation, due in large measure to differences in presynaptic properties. We investigated quantal release properties, calcium signals, and ultrastructure of presynaptic terminals to elucidate factors that could account for the physiological differences. Focal macropatch electrodes were placed over individual visualized terminal varicosities to obtain records of quantal contributions to the excitatory junctional current (EJC). At low frequencies of activation, mean quantal content is greater for proximal than for central varicosities. This difference is due to a higher probability of release per synapse, and not to a larger number of active synapses. Recorded varicosities were labeled with fluorescent beads deposited by the electrode. These beads adhered to the muscle fibers, outlining the recorded site for subsequent serial thin sectioning and reconstruction from electron micrographs. Comparisons of structure and function were made for individual varicosities. The number of active zones per terminal surface area and the number of synapses with multiple active zones (complex synapses) were greater in high output varicosities. Calcium indicators were loaded into proximal and central nerve terminals by axonal injection to compare the relative differences in calcium buildup during stimulation. Presynaptic calcium signals were larger for proximal varicosities than for central varicosities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790907 TI - Neurotrophins and the neuroendocrine brain: different neurotrophins sustain anatomically and functionally segregated subsets of hypothalamic dopaminergic neurons. AB - Hypothalamic neurons control a variety of important hormonal and behavioral functions. Little is known, however, about the neurotrophic factors that these neurons may require for survival and/or maintenance of their differentiated functions. We conducted experiments to examine this issue, utilizing a combination of immunohistochemical, in situ hybridization and cell culture approaches. We found that the low affinity receptor for nerve growth factor (p75 NGFR) is present in small subsets of hypothalamic peptidergic neurons identified as such by their content of galanin, luteinizing hormone-releasing hormone (LHRH) and vasointestinal peptide (VIP). More prominently, however, examination of hypothalamic dopaminergic (DA) neurons for the presence of p75 NGFR-like immunoreactivity revealed that the receptor was present on tyrosine hydroxylase (TH)-positive neurons of the zona incerta and periventricular region, but not on neuroendocrine DA neurons of the tuberoinfundibular region. In situ hybridization experiments using a p75 NGFR cRNA confirmed this distribution. Regardless of the presence or absence of p75 NGFR, neither DA group expresses trkA mRNA, indicating that these two major hypothalamic subsets of DNA neurons are NGF-insensitive. A substantial fraction of TH mRNA-positive cells in the zona incerta expresses trkB mRNA, which encodes the receptor for brain derived neurotrophic factor (BDNF); in turn BDNF supports the in vitro survival of hypothalamic TH neurons bearing p75 NGFR, suggesting that BDNF is trophic for DNA neurons of the zona incerta. In contrast, tuberoinfundibular DA neurons do not express trkB mRNA, but some have trkC mRNA, which encodes the receptor for neurotrophin-3 (NT-3). The in vitro survival of TH neurons devoid of p75-NGFR is supported by NT-3, implying that NT 3 may be trophic for a subset of tuberoinfundibular DA neurons. These results suggest that, in spite of expressing an identical neurotransmitter phenotype, anatomically and functionally segregated DA neurons of the neurodendocrine brain are sustained by different neurotrophic factors. PMID- 7790908 TI - Kainic acid-induced neuronal death is associated with DNA damage and a unique immediate-early gene response in c-fos-lacZ transgenic rats. AB - Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death. Following treatment of transgenic rats with KA there was a protracted expression of Fos-lacZ that lasted for 2-3 d. In contrast, PTZ elicited a transient increase in the transgene product that lasted about 6 hr. Normally, Fos and Fos-lacZ were detected only in neuronal nuclei. However, 6 hr following kainic acid (but not PTZ) administration, beta-galactosidase activity appeared in the cytoplasm of neurons within vulnerable regions (as determined by the terminal transferase biotinylated-UTP nick end labeling (TUNEL) procedure). Like c-fos, transcripts for other cIEGs were elevated for longer periods in the KA-treated rat hippocampus. In addition, fra-1 and fra-2 were only induced in the KA-treated rat. These changes in mRNA levels were paralleled by a sustained increase in AP-1 DNA binding activity. Thus, quantitative and qualitative changes in AP-1 DNA binding complexes accompany neurotoxic cell death that are not observed following seizures. PMID- 7790909 TI - V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. AB - To develop and validate a vasopressin (AVP) receptor knockdown strategy, we infused an antisense oligodeoxynucleotide to the V1 subtype mRNA into the septum of male rats with osmotic minipumps and measured behavioral, cellular and molecular parameters. Compared to vehicle and scrambled-sequence oligo controls, chronic antisense administration for up to 4 d diminished the ability of the animals to distinguish a previously exposed juvenile from a novel one and to respond to exogenous AVP (1 ng/5 microliters, intracerebroventricular) with an improved social memory. Furthermore, anxiety-related behavior was reduced. As measured in the behaviorally tested rats, antisense treatment resulted in a reduced binding of radiolabeled AVP in the septum, but not in other limbic brain areas (receptor autoradiography), and an increased amount of V1 receptor mRNA (reverse transcriptase PCR), indicating translational arrest and ongoing transcriptional activity. In sense oligo-treated rats, on the other hand, both the social and the anxiety-related behavior scores lay between levels obtained in control and antisense-treated animals. These sense-treated rats showed a slightly reduced V1 receptor density in the septum and reduced receptor mRNA levels, indicating hybridization of the sense oligo to the DNA. The data show the potential of antisense targeting to further reveal relationships between local gene expression, neuropeptide-receptor interactions in distinct brain areas, and behavioral performance. PMID- 7790910 TI - Nocodazole-dependent transport, and brefeldin A--sensitive processing and sorting, of newly synthesized membrane proteins in cultured neurons. AB - The envelope glycoproteins of Semliki Forest virus (SFV), Vesicular Stomatitis virus (VSV), and Influenza Fowl Plague virus (FPV) are vectorially targeted in neurons to the plasma membrane of dendrites (SFV and VSV) and axons (FPV). To gain insight into the mechanisms responsible for such polarized delivery we have examined the effects on neurons of nocodazole and brefeldin A (BFA), which are known to cause microtubule depolymerization and disassembly of the Golgi apparatus, respectively. Nocodazole treatment blocked transport of all viral glycoproteins to both axons and dendrites. BFA treatment induced disruption of the Golgi complex, including the trans-Golgi network (TGN), and tubulation of endosomes. However, the delivery of the SFV and FPV glycoproteins to the cell surface was not affected significantly by BFA, although processing and sorting were altered, as revealed by surface biotinylation and immunofluorescence microscopy of fixed nonpermeabilized cells. These results demonstrate the involvement of microtubules in axonal and dendritic transport of integral membrane glycoproteins, and the existence of a BFA-sensitive component in the sorting but not in the transport machinery. PMID- 7790911 TI - Effects of estradiol and progesterone on voltage-gated calcium and potassium conductances in rat CA1 hippocampal neurons. AB - In this study we recorded voltage gated Ca and K conductances with patch electrodes in hippocampal slices from female rats, which were ovariectomized (OVX) 1 week before the experiment. One experimental group was primed with estradiol at day 3 and 4 after OVX and received progesterone 4 hr before the start of the experiment. The second group was treated with estradiol at day 3 and 4, but received vehicle at the day of the experiment. The third group was not treated with hormones (only vehicle injections). We observed that the amplitude of both sustained and transient Ca currents were significantly enhanced in CA1 pyramidal neurons recorded in tissue from estradiol primed rats receiving progesterone when compared to the nontreated OVX controls; without estradiol priming Ca current amplitudes were small. Current amplitudes in tissue from rats treated with estradiol only, were at intermediate values. The voltage for half maximal steady state inactivation of the transient Ca current was at a less negative value for the estradiol/progesterone treated group in comparison to the OVX controls. Input resistances of the cells, and voltage or kinetic properties of the currents as recorded under these conditions were comparable for the three groups. Characteristics of two voltage gated K conductances, that is, the transient IA and the delayed rectifier, displayed no consistent differences for the three experimental groups. We conclude that long-term modulation of estradiol and progesterone levels alters the Ca but not the K currents that were tested in CA1 pyramidal neurons. These alterations may be linked to steroid-induced morphological changes in dendrites of CA1 pyramidal cells. PMID- 7790912 TI - The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons. AB - Potassium channels play major roles in the regulation of many aspects of neuronal excitability. These channels are particularly well suited for such multiplicity of roles since there is a large diversity of channel types. This diversity contributes to the ability of specific neurons (and possibly different regions of the same neuron) to respond uniquely to a given input. Neuronal integration depends on the local response of spatially segregated inputs to the cell and the communication of these integration centers with the axon. Therefore, the functional implications of a given set of K+ channels varies depending on their precise location on the neuronal surface. Site-specific antibodies were utilized to characterize the distribution of KV3.1b, a subunit of voltage-gated K+ channels in CNS neurons. KV3.1b subunits are expressed in specific neuronal populations of the rat brain, such as cerebellar granule cells, projecting neurons of deep cerebellar nuclei, the substantia nigra pars-reticulata, the globus pallidus, and the ventral thalamus (reticular thalamic nucleus, ventral lateral geniculate and zona incerta). The KV3.1b protein is also present in various neuronal populations involved in the processing of auditory signals, including the inferior colliculus, the nuclei of the lateral lemniscus, the superior olive, and some parts of the cochlear nuclei; as well as in several other neuronal groups in the brainstem (e.g., in the oculomotor nucleus, the pontine nuclei, the reticulotegmental nucleus of the pons, trigeminal and vestibular nuclei, and the reticular formation) and subsets of neurons in the neocortex, the hippocampus and the caudate-putamen shown by double staining to correspond to neurons containing parvalbumin. KV3.1b subunits are localized predominantly in somatic and axonal membranes (particularly in axonal terminal fields) but are much less prominent in dendritic arborizations. This distribution is different than that of other subunits of voltage gated K+ channels and is consistent with a role in the modulation of action potentials. KV3.1b proteins have a cellular and subcellular distribution different than the related KV3.2 subunits which express in Xenopus oocytes currents similar to those expressed by KV3.1b. PMID- 7790913 TI - Bilateral control of hindlimb scratching in the spinal turtle: contralateral spinal circuitry contributes to the normal ipsilateral motor pattern of fictive rostral scratching. AB - In a spinal turtle, unilateral stimulation in the rostral scratch receptive field elicited rhythmic fictive rostral scratching in ipsilateral hindlimb motor neurons; contralateral hip motor activity was also rhythmic and out-of-phase with ipsilateral hip motor activity. When left and right rostral scratch receptive fields were stimulated simultaneously, bilateral rhythmic fictive rostral scratching was produced; left hindlimb scratching was out-of-phase with right hindlimb scratching. Thus, spinal circuits coordinate interlimb phase during bilateral fictive scratching. We examined the contributions of contralateral spinal circuitry to the normal pattern of right hindlimb fictive rostral scratching by removing the left halves of the D7 segment and the hindlimb enlargement (D8-S2 segments). After left-hemicord removal, stimulation in the right rostral scratch receptive field usually elicited a variation of rostral scratching with rhythmic right hip flexor activity and no right hip extensor activity; thus, right hip flexor rhythm generation does not require left hindlimb enlargement circuitry. Normal right hindlimb rostral scratching with rhythmic alternation between hip flexor and extensor activities was rarely observed; thus, contralateral spinal circuitry contributes to the production of normal ipsilateral fictive rostral scratching. After left-hemicord removal, stimulation in the left rostral scratch receptive field elicited rhythmic right hip extensor activity; thus, contralateral spinal circuitry can generate a hip extensor rhythm during ipsilateral rostral scratch receptive field stimulation. Our observations and those of Berkowitz and Stein (1994a,b) support the concept that an ipsilateral hindlimb's normal rostral scratch motor pattern is generated by a modular central pattern generator that is bilaterally distributed in the spinal cord. PMID- 7790914 TI - Growth cones are actively influenced by substrate-bound adhesion molecules. AB - As axons advance to appropriate target tissues during development, their growth cones encounter a variety of cell adhesion molecules (CAMs) and extracellular matrix molecules (ECM molecules). Purified CAMs and ECM molecules influence neurite outgrowth in vitro and are thought to have a similar function in vivo. For example, when retinal ganglion cell (RGC) neurons are grown on different CAM and ECM molecule substrates in vitro, their growth cones display distinctive morphologies (Payne et al., 1992). Similarly, RGC growth cones in vivo have distinctive shapes at different points in the pathway from the eye to the tectum, suggesting the presence of localized cues that determine growth cone behaviors such as pathway selection at choice points. In this report, time-lapse video microscopy was utilized to examine dynamic transformations of RGC growth cones as they progressed from L1/8D9, N-cadherin, or laminin onto a different substrate. Contact made by the leading edge of a growth cone with a new substrate resulted in a rapid and dramatic alteration in growth cone morphology. In some cases, the changes encompassed the entire growth cone including those regions not in direct contact with the new substrate. In addition, the growth cones displayed a variety of behavioral responses that were dependent upon the order of substrate contact. These studies demonstrate that growth cones are actively affected by the substrate, and suggest that abrupt changes in the molecular composition of the growth cone environment are influential during axonal pathfinding. PMID- 7790915 TI - Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors. AB - Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine. In addition, patchclamp experiments reveal that these cells are electrically excitable. Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro. The results suggest that these cells originate from the "stem cell" compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation. PMID- 7790917 TI - Quantification of excitatory amino acid uptake at intact glutamatergic synapses by immunocytochemistry of exogenous D-aspartate. AB - To study the localization and efficiency of glutamate/aspartate membrane transport in the vicinity of intact glutamatergic synapses, the avascular lamprey spinal cord was incubated with D-aspartate, a metabolically inert transporter substrate. The exogenous D-aspartate was localized by immunocytochemistry after aldehyde fixation. Incubation at 50 or 500 microM D-aspartate for 1 hr caused a prominent D-aspartate labeling of glial processes at glutamatergic synapses, while presynaptic axons and postsynaptic dendrites remained unlabeled. The glial processes surrounding glutamatergic sensory axons with a predominantly tonical firing pattern contained significantly higher levels of D-aspartate than did processes surrounding glutamatergic reticulospinal axons, which fire rarely and in brief bursts. Preparations incubated for 10 hr with 500 microM D-aspartate showed D-aspartate immunolabeling in glia as well as in the two types of glutamatergic axon, but no evidence was obtained for uptake into synaptic vesicles. Nor was such evidence obtained after high-frequency electrical stimulation. The observations suggest that excitatory amino acids delivered diffusely to the extracellular space in the intact CNS are transported almost exclusively into glia. The avid uptake in glial processes, combined with their spatial arrangement around glutamatergic synapses, appears to limit the access of exogenous D-aspartate to the nerve terminal glutamate/aspartate transporter. In physiological conditions, the glial processes are likely to impede the exchange of glutamate between the synaptic cleft and the rest of the extracellular space. The transport was more efficient in glial processes located near tonically active synapses than in ones located near synapses releasing transmitter sporadically. D Aspartate is not a substrate of vesicular glutamate transport sites at these intact synapses. PMID- 7790918 TI - Expression of molecules associated with neuronal plasticity in the striatum after aspiration and thermocoagulatory lesions of the cerebral cortex in adult rats. AB - Like the hippocampus, the striatum receives excitatory afferents from the cerebral cortex but, in the case of the striatum, very little is known about the molecular events associated with plasticity after lesions of this pathway. Using immunohistochemical techniques, we have examined the effects of cortical lesions induced either by aspiration of the frontoparietal cortex or by thermocoagulation of pial blood vessels on axonal and glial molecules associated with neuronal plasticity in the striatum. The growth associated protein GAP-43, a molecule present in axons and growth cones, decreased in the dorsolateral striatum after aspiration but not after thermocoagulatory lesions. In contrast, synaptophysin, a marker of synaptic vesicles, remained unchanged in the denervated striatum after both types of lesions. Immunostaining for basic fibroblast growth factor (bFGF) markedly decreased in striatal astrocytes after both lesions, despite an increased staining for glial fibrillary acidic protein (GFAP). The adhesion molecules tenascin, chondroitin sulfate proteoglycans, highly polysialylated neural cell adhesion molecule (PSA-NCAM), and laminin did not change significantly in the gray matter of the dorsolateral striatum after either type of lesion. These effects differed from those observed after partial denervation of the hippocampus and spinal cord, revealing marked regional differences in the response of axonal and glial proteins to afferent lesions. In addition, the results further indicate that cortical lesions have both similar and distinct consequences, depending on the procedure by which the lesions are induced, suggesting that cortical lesions associated with different types of pathology may differentially affect subcortical structures. PMID- 7790916 TI - Activation of a nonselective cationic conductance by metabotropic glutamatergic and muscarinic agonists in CA3 pyramidal neurons of the rat hippocampus. AB - We have characterized a cationic membrane conductance activated by metabotropic glutamatergic and muscarinic cholinergic agonists in CA3 neurons in hippocampal slice cultures using the patch-clamp technique. When the potassium concentration in the superfusing fluid was raised above 5 mM, a biphasic current was observed in cells held at -60 mV in response to stimulation of postsynaptic metabotropic glutamate receptors (mGluRs) with 1S,3R-ACPD (50 microM) or muscarinic receptors with methacholine (MCh, 5 microM). The initial inward component was due to an increase in a cationic membrane conductance as determined by its reversal potential and its sensitivity to changes in extracellular K+ or Na+. The conductance underlying this current displayed no apparent voltage sensitivity over the range -120 to -50 mV. The response was reduced by extracellular application of Ba2+, Cd2+, Mg2+, or TEA, whereas extracellular Cs+ or loading cells with BAPTA or Cs+ did not affect the current. The effects of 1S,3R-ACPD were reversibly inhibited by bath-applied MCPG, an antagonist at mGluRs. Experiments with atropine and pirenzepine indicated that non-M1 muscarinic receptors mediated the MCh-induced current. A decrease in a resting leak potassium conductance (IK,leak) was responsible for the late component of the 1S,3R-ACPD- and MCh-induced response, seen as an outward current in the bathing solution with high K+ concentration. Loading cells with GDP beta S, GTP gamma S, or GTP did not alter the cationic current, while, in the same cells, the reduction in IKleak was abolished or irreversibly activated. Single-channel recordings of cationic channel activity in the cell-attached configuration provided evidence for the requirement of second messengers in coupling these receptors to the cationic channels. The data indicate that in addition to the previously described reduction of IK,leak, IM, and IAHP, both 1S,3R-ACPD and MCh activate a nonselective cationic conductance that is clearly revealed upon elevating external K+ concentration. This current is mediated by activation of metabotropic receptors, although no evidence could be obtained to show an involvement of G-proteins. PMID- 7790919 TI - Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons. AB - Many of the nonlinear membrane properties displayed by neostriatal spiny projection neurons are conferred by their voltage-gated potassium (K+) currents, including an inwardly rectifying current (IKir), fast (IAt), and slowly (IAs) inactivating A-currents, and a slow, noninactivating current. The relative contribution of these K+ currents to the pronounced inward and outward rectification of the current-voltage (I-V) relationship of spiny neurons was investigated in a neostriatal slice preparation. Manipulation of the equilibrium potential for K+ (EK) showed that the voltage dependence of activation of inward rectification was identical to that of IKir. In addition, application of barium (100 microM), which is known to reduce IKir in a time- and voltage-dependent manner, had equivalent effects on inward rectification. Subsequent application of cesium (3 mM) or tetraethylammonium (TEA, 25 mM) blocked inward rectification in a solely voltage-dependent fashion consistent with the action of these blockers on IKir. Administration of 4-aminopyridine (4-AP, 100 microM) at concentrations that selectively depress IAs, reduced outward rectification of spiny neurons at subthreshold membrane potentials. Higher concentrations of 4-AP (2 mM), which block both IAs and IAt, revealed an early transient overshoot in voltage deflections at potentials near spike threshold, but rectification persisted at the end of the responses. The transient overshoot and the residual rectification were eliminated by TEA (25 mM), a blocker of the slow, noninactivating K+ current. Collectively, these results indicate that all three depolarization activated K+ currents contribute to outward rectification at different times and membrane potentials defined by their voltage dependence of activation and kinetics of inactivation. The spontaneous activity of neostriatal spiny neurons recorded in intact animals is characterized by sustained and limited shifts in membrane potential from relatively hyperpolarized potentials to depolarized potentials near spike threshold. The present data suggest that the hyperpolarized state is determined principally by IKir and the limits on the depolarized state are defined by IAf, IAs, and the noninactivating current. These outward K+ currents also are hypothesized to govern the spike discharge characteristics once the depolarized state has been reached. PMID- 7790920 TI - Electrical activity and calcium influx regulate ion channel development in embryonic Xenopus skeletal muscle. AB - The development of electrical excitability involves complex coordinated changes in ion channel activity. Part of this coordination appears to be due to the fact that the expression of some channels is dependent on electrical activity mediated by other channel types. For example, we have previously shown that normal potassium current development in embryonic skeletal muscle cells of the frog Xenopus laevis is dependent on sodium channel activity. To examine the interrelationships between the development of different ionic currents, we have made a detailed study of electrical development in cultured Xenopus myocytes using whole-cell patch-clamp recording. The initial expression of potassium, sodium, and calcium currents is followed by a brief period during which the densities of potassium currents decrease, while at the same time sodium and calcium current densities continue to increase, which may increase electrical excitability during this time. The normal developmental increase in both potassium and sodium currents is inhibited by the sodium channel blocker tetrodotoxin, suggesting that electrical activity normally stimulates the expression of both these currents. These effects of electrical activity appear to be mediated via activation of voltage-gated calcium channels. We suggest that the developmental acquisition of sodium and calcium channels by these cells, possibly coupled with a transient decrease in potassium current density, lead to an increase in electrical excitability and calcium entry, and that this calcium entry provides a critical developmental cue controlling the subsequent development of mature electrical properties. PMID- 7790921 TI - Mechanism for modulation of nicotinic acetylcholine receptors that can influence synaptic transmission. AB - Only recently has it been appreciated that neuronal nicotinic ACh receptors (NnAChRs) are highly permeable to Ca2+ and are modulated by Ca2+ in a dose dependent manner. These findings suggest that Ca2+ could have roles in cholinergic synaptic plasticity. We report a possible mechanism for Ca(2+) initiated synaptic plasticity that differs from the intracellular Ca2+ cascade associated with plasticity of glutamatergic synapses. Rapid changes in external Ca2+ modulate cholinergic spontaneous synaptic currents in superior cervical ganglionic sympathetic neurons. Inhibition of cholinergic currents by chlorisondamine, which blocks only open channels and becomes trapped in the pore, showed that the modulation is not by a mechanism that activates a previously unresponsive population of NnAChRs. Rather, single-channel recordings with ganglionic NnAChRs from chromaffin cells indicated that Ca2+ directly alters the probability of the channels being open. We hypothesize from the results that activity-dependent decreases in external Ca2+, which occur throughout the nervous system, could directly underlie a rapid negative-feedback mechanism that decreases the responsiveness of NnAChRs at synapses. When external Ca2+ is decreased, presynaptic Ca2+ currents and transmitter release also are diminished. Thus, several mechanisms could combine to potently and rapidly depress synaptic nicotinic receptors until the external Ca2+ concentration recovers. PMID- 7790922 TI - Dopamine-modulated potassium channels on rat striatal neurons: specific activation and cellular expression. AB - We have used cell-attached patch-clamp electrophysiology to characterize the activation and distribution of an 85 pS K+ channel on freshly dissociated rat striatal (caudate-putamen) neurons. In recordings from 643 cells, openings of this channel showed an absolute dependence on the presence of dopamine or the D2 like dopamine receptor agonist quinpirole in the cell-attached patch pipette, but were never seen when the D2 antagonist domperidone was applied along with quinpirole, or in the absence of drug. This channel displayed inward rectification at depolarized membrane potentials, but its activation was otherwise voltage insensitive. It was largely restricted to a subset of dissociated cells with diameters > or = 10 microns, with channel openings seen in about 25% of patches. When present, there were typically multiple channels per patch. Cells of this size were immunocytochemically stained for neuron-specific enolase but not glial fibrillary acidic protein; about 40% were also labeled for gamma-amino butyric acid (GABA) and about 60% for NADPH diaphorase, with GABAergic cells displaying a shape most similar to that of cells expressing the channel. A large number of distinct types of other channels were also present, comprising inwardly rectifying channels of 5-35 pS conductance and voltage activated channels of 100-250 pS, but the frequencies of occurrence and fractional open times of these channels were independent of the presence or absence of dopaminergic agonists. Thus, the 85 pS K+ channel uniquely requires activation by a D2-like dopamine receptor on rat striatal neurons, and is selectively expressed by a subset of these cells, which are most likely to be GABAergic neurons. PMID- 7790923 TI - Lamina-specific expression of adhesion molecules in developing chick optic tectum. AB - The optic tectum is the major synaptic target of retinal axons in birds. In the chick, retinal ganglion cell axons enter the optic tectum through a superficial lamina (the stratum opticum), extended branches into deeper laminae, and arborize in specific "retinorecipient" laminae, where they form synapses. Studies using an organotypic culture system have provided evidence that the tectum bears a series of distinct, lamina-specific, cell surface-associated cues that direct these axonal behaviors (Yamagata and Sanes, 1995). Here, we have used a panel of antibodies to 30 membrane and matrix components to ask whether known adhesive molecules are distributed in lamina-specific patterns. Among many spatiotemporal pattern of expression documented, three were particularly noteworthy: (1) The cell adhesion molecules NgCAM/L1 and TAG-1/axonin-1 were concentrated in the stratum opticum. (2) SC1/JC7/DM-GRASP/BEN, N-cadherin, neuropilin, polysialylated N-CAM, and glycoconjugates recognized by the lectin VVA-B4 were concentrated in retinorecipient laminae. (3) Neurofascin, tenascin-C/cytotactin, and a matrix molecule defined by the "Sigma" antibody were present at highest levels in areas that border the retinorecipient laminae. Some members of each group (NgCAM/L1, TAG-1/axonin, SC1/JC7, polysialic acid, VVA-B4-receptors, and neurofascin) appeared on schedule and in lamina-restricted patterns in tecta from embryos that had been enucleated before retinal axons left the eye. Thus, molecules in these three categories could provide signals to retinal axons that promote extension through the stratum opticum, induce arborization or synaptogenesis in retinorecipient laminae, and prevent sprouting into adjoining laminae. Interestingly, N-cadherin accumulated in retinorecipient laminae only following the onset of synapse formation, and failed to accumulate in enucleated tecta. Immunoelectron microscopy of normal tecta demonstrated the presence of N-cadherin in the synaptic cleft, suggesting a role for this molecule in synaptic maintenance. PMID- 7790924 TI - Kinase and phosphatase activities intimately associated with a reconstituted calcium-dependent potassium channel. AB - Type-2 calcium-dependent potassium (KCa) channels from mammalian brain, reconstituted into planar phospholipid bilayers, are modulated by ATP or ATP analogs via an endogenous protein kinase activity intimately associated with the channel (Chung et al., 1991). We show here that the endogenous protein kinase activity is protein kinase C (PKC)-like because (1) modulation by ATP can be mimicked by exogenous PKC, and (2) the effects of ATP can be blocked by PKC(19 36), a specific peptide inhibitor of PKC. Furthermore, adding the PKC inhibitor peptide after the addition of ATP reverses the modulation produced by ATP, suggesting that there is a phosphoprotein phosphatase activity closely associated with type-2 KCa channels. Consistent with this idea is the finding that microcystin, a non-specific phosphatase inhibitor, enhances the modulation of KCa channel activity by ATP. Inhibitor-1, a specific protein inhibitor of phosphoprotein phosphatase-1, also enhances the effect of ATP, suggesting that the endogenous phosphatase activity is phosphatase-1-like. The results imply that type-2 KCa channels exist as part of a regulatory complex that includes a PKC like protein kinase and a phosphatase-1-like phosphoprotein phosphatase, both of which participate in the modulation of channel function. PMID- 7790926 TI - Evidence for glycine modulation of excitatory synaptic inputs to retinal ganglion cells. AB - The actions of glycine on the NMDA receptor-mediated synaptic responses of ganglion cells were studied in the tiger salamander retinal slice. Ganglion cell excitatory postsynaptic currents (EPSCs) were elicited either by exciting bipolar cells with potassium puffs or by light stimulation, and were measured using whole cell patch-clamp techniques. Increasing bath glycine concentrations to 10 microM had little effect on the amplitude of the puff-evoked EPSCs, indicating either that synaptic glycine concentrations were saturating or that the added glycine was buffered by uptake mechanisms. However, 5,7-dichlorokynurenic acid (5,7-DCK), an antagonist for the glycine site on the NMDA receptor, reduced the ganglion cell responses to NMDA puffs, and reduced the potassium puff- and light-elicited EPSCs. The IC50 values for 5,7-DCK became larger with increasing glycine concentrations, but not with increasing NMDA concentrations, indicating that 5,7 DCK acted at the glycine site. The IC50 values for 5,7-DCK were increased with stronger potassium puffs or light stimuli, suggesting that synaptic glycine levels increased with the strength of the stimuli. EPSCs measured in ON-OFF ganglion cells at light ON and OFF were reduced by 5,7-DCK. For dim light stimuli, the IC50 values were lower for the OFF EPSCs compared to the ON EPSCs, indicating that glycine concentrations were different at the times of OFF and ON activity. Estimates of synaptic glycine concentrations suggest that for dim light stimuli, concentrations at the OFF synapses were not saturated, but concentrations at the ON synapses were saturated. PMID- 7790925 TI - Differential regulation of sympathetic neuron neuropeptide Y and catecholamine content and secretion. AB - Cultured principal neurons of the superior cervical ganglion (SCG), which coexpress high levels of catecholamines and neuropeptide Y (NPY), were used as a model to simultaneously examine whether sympathetic neuronal peptide and transmitter content or secretion are differentially regulated. Accumulation of NPY immunoreactivity and the dopamine metabolites DOPAC and HVA in SCG neuronal conditioned culture medium was used as an index of NPY and catecholamine secretion, respectively. Release of NPY and catecholamines was linear with time; SCG neurons exhibited a basal NPY secretory rate of approximately 0.9-3 fmol NPY immunoreactivity/10(4) cells/hr, and basal DOPAC plus HVA accumulation was about 10-20 pmol total metabolites/10(4) cells/hr. While sympathetic neuronal NPY and total catecholamine cell content increased more than 6-10-fold by 14 d of culture, secretion remained constant. Depolarization stimulated the rate of NPY secretion 18-fold, whereas medium catecholamine metabolite levels increased 3 fold. Activation of intracellular signaling pathways was shown to be an important point of regulation of sympathetic neuron peptide and transmitter content and secretion. Differential regulation of SCG neuron NPY and catecholamine expression was second messenger system specific. Activation of the protein kinase A pathway with the cAMP analog dibutyryl cAMP, or the adenylyl cyclase activator forskolin, produced a concentration-dependent, sustained stimulation of NPY secretion; maximal stimulation resulted in decreased cellular NPY content. Parallel stimulated neuronal catecholamine release was observed, but in contrast to NPY, total cellular catecholamine content was also increased. Regulation of the protein kinase C pathway with phorbol myristate acetate (PMA) stimulated SCG neuronal NPY secretion to a lesser degree than activation of protein kinase A, but did not alter cellular NPY levels. PMA minimally stimulated catecholamine release and content. NPY secretion induced by the calcium ionophore A23187 was paralleled by a concomitant decrease in cellular NPY. A23187 decreased catecholamine release, but did not change cellular total catecholamine levels. The magnitude of the secretory responses of sympathetic neurons to these regulators was far greater than changes in NPY or catecholamine content, biosynthesis or mRNA levels, suggesting that release is a primary site of regulation. The independent regulation of sympathetic neuronal NPY and catecholamine content and release is consistent with the fundamental differences in the biosynthetic pathways, vesicular compartmentalization, uptake and metabolism of neuropeptides and neurotransmitters. PMID- 7790927 TI - Developmental changes in presynaptic calcium channels coupled to glutamate release in cultured rat hippocampal neurons. AB - Excitatory synaptic transmission in the hippocampus involves the participation of at least two types of presynaptic Ca2+ channels, N-type channels sensitive to omega-conotoxin GVIA (omega-CTx GVIA) and Q-type channels sensitive to omega agatoxin IVA (omega-Aga IVA). Hippocampal pyramidal neurons in cell culture were used to examine the participation of these two classes of channels at different stages of synapse development. Specific Ca2+ channel toxins were used to block presynaptic Ca2+ channels while whole-cell voltage-clamp recordings were used to record evoked EPSCs in postsynaptic neurons. At immature synapses (cells in culture for 10-15 d), omega-CTx GVIA (1-5 microM) blocked transmission by more than 80% while omega-Aga IVA (1 microM) was less effective. In older cultures, however, omega-Aga IVA (1 microM) was more effective than omega-CTx GVIA (1-5 microM) in blocking synaptic transmission. The pharmacological properties of the omega-Aga IVA sensitive component of synaptic transmission were examined in more detail using omega-Aga IVA and omega-conotoxin MVIIC (omega-CTx MVIIC). The properties of this component of transmitter release indicated that a Q-type Ca2+ channel was involved in presynaptic Ca2+ entry. The results suggest that different classes of presynaptic Ca2+ channels begin to participate in transmitter release at different times during synapse development and maturation. PMID- 7790928 TI - Cell cycle progression in gentamicin-damaged avian cochleas. AB - Hair cells, the sensory receptors of the auditory, vestibular, and lateral-line organs, may be damaged by a number of agents including aminoglycoside antibiotics and severe overstimulation. In the avian cochlea, lost hair cells can be replaced by regeneration. These new hair cells appear to be derived from a support cell precursor which is stimulated to divide by events associated with hair cell loss. Little is known about the timing and sequencing of events leading to new hair cell production. In this study cell cycle-associated events in the avian cochlea were analyzed at early and late time intervals following a single high dose of gentamicin. This single dose protocol has been shown to consistently result in extensive morphological damage and hair cell loss in the proximal region of the cochlea while sparing a morphologically undamaged distal cochlear region. This allowed for the differential analysis of the underlying support cell populations with respect to local hair cell loss. Three cell cycle associated markers were used to evaluate which cells entered and progressed through the cell cycle: statin, a G0 associated nuclear marker; proliferating cell nuclear antigen (PCNA), a G1, S and G2 associated marker; and 5-bromodeoxyuridine (BrdU), an S phase associated marker. Using these markers we found evidence for reversible changes in cell cycle status throughout the cochlea, while progression through S phase and mitosis was restricted to the region of the cochlea which sustained hair cell loss. PMID- 7790930 TI - Regulation of a potassium conductance in rat midbrain dopamine neurons by intracellular adenosine triphosphate (ATP) and the sulfonylureas tolbutamide and glibenclamide. AB - The presence of adenosine triphosphate-regulated potassium channels (K-ATPs) in midbrain dopamine neurons is currently in dispute. This was investigated using whole-cell patch-clamp recordings from dopamine neurons in slices of midbrain from 9-12-d-old rats. Intracellular dialysis with Mg2+ ATP-free solutions resulted in a membrane hyperpolarization (14 +/- 6 mV), or outward current (102 +/- 27 pA) in voltage clamp, which developed over 14 +/- 1.6 min. These hyperpolarizations and outward currents were reversed by the K-ATP-blocking sulfonylureas tolbutamide (100 microM) and glibenclamide (3 microM). This sulfonylurea-sensitive outward current was associated with an increase in a nonrectifying (between -50 and -130 mV) conductance of approximately 2 nS, with a reversal potential of -100 mV (in 2.5 mM extracellular potassium), consistent with a potassium conductance increase. When the dialyzate contained Mg2+ATP (2 mM), no slowly developing hyperpolarization or outward current occurred, and tolbutamide (200 microM) and glibenclamide (10 microM) did not affect membrane potential or current. Additionally, the "potassium channel activators" (KCAs) lemakalim (200 microM) and pinacidil (50 microM) were also without effect on the membrane potential or holding current in these cells. The hyperpolarizations and outward currents caused by baclofen and quinpirole, agonists at GABAB and D2 receptors, respectively, were neither blocked by sulfonylureas nor occluded by the current resulting from depletion of intracellular ATP. Thus, these K-ATPs appear independent of the potassium channels coupled to GABAB and D2 receptors in these cells. This ATP-regulated potassium conductance may constitute a protective mechanism during anoxia or hypoglycemia, by restricting membrane depolarization of dopamine neurons when intracellular ATP levels fall. PMID- 7790929 TI - Gas chromatographic-mass fragmentographic quantitation of 3 alpha-hydroxy-5 alpha pregnan-20-one (allopregnanolone) and its precursors in blood and brain of adrenalectomized and castrated rats. AB - Coupling high performance liquid chromatography with gas chromatography-mass fragmentography has made it possible to simultaneously measure subpicomolar concentrations of allopregnanolone and its precursors, pregnenolone, progesterone and 5 alpha-dihydroprogesterone (5 alpha-DHP) in various brain areas. Allopregnanolone was measured in the brain of adrenalectomized/castrated (ADX/CX) rats in nanomolar concentrations long after peripheral sources of allopregnanolone were removed. A partial decrease (approximately 30%) in the content of allopregnanolone was found in the brains of ADX/CX rats compared to sham-operated rats. Moreover, the content of allopregnanolone in brains of sham operated as well as ADX/CX rats was nonuniformly distributed (olfactory bulb > striatum > cortex > hippocampus) and was one to two orders of magnitude higher than in plasma or liver. Infusion of pregnenolone sulfate in ADX/CX rats elicited a fourfold increase in 5 alpha-DHP and progesterone content and a seven- to eightfold increase in the content of allopregnanolone in brain but not in liver or plasma. Furthermore, the content of allopregnanolone in brain increased to the same extent in both sham-operated and ADX/CX rats following pregnenolone sulfate infusion. The 5 alpha-reductase inhibitor, (17 beta)17[[bis(1 methylethyl)amino]carbonyl] androstane-3,5-diene-3-carboxylic acid (SKF 105111), reduced the brain content of allopregnanolone and blocked the increased formation of allopregnanolone in brain following pregnenolone sulfate infusion. The results clearly demonstrate that the synthesis of allopregnanolone from 5 alpha-DHP and progesterone occurs in the brain and that a significant amount of allopregnanolone is synthesized locally in brain from its precursors. These experiments suggest that the brain, like adrenals and gonads, is a steroidogenic organ which produces allopregnanolone as one of its own most important physiologically relevant steroids. PMID- 7790931 TI - Disconnection of intracortical synaptic linkages disrupts synchronization of a slow oscillation. AB - The intracortical synaptic linkages underlying the synchronization of a recently described slow (< 1 Hz) oscillation (Steriade et al., 1993b,c) were investigated in anesthetized cats by means of multisite extra- and intracellular recordings, including dual impalements, from rostral and caudal sites in the association cortical suprasylvian and marginal gyri, before and after reversible lidocaine inactivation or transections in the middle suprasylvian gyrus. Stimulus-evoked responses revealed that the rostral and caudal suprasylvian foci are reciprocally connected, with a preference for posterior-to-anterior responses. Lidocaine infusion between the stimulating and recording sites disrupted the intracortical synaptic linkage, while leaving unaffected the responses at the sites close to the stimulating electrodes. The high coherence between slowly oscillating field potentials and intracellular activities recorded from anterior and posterior suprasylvian foci was lost after reversible inactivation or transections in the middle suprasylvian gyrus, whereas the synchrony between adjacent foci within the anterior or posterior areas was preserved. Two to four hours after inactivation or transection the synchrony between all channels was totally or partially recovered. We introduced the synchrony coefficient (SyCo) and calculated the SyCo for closely located and distant sites. Lidocaine infusion or transection did not affect the SyCo between leads placed on the same site, but significantly (60%) decreased the SyCo between channels separated by the functionally inactivated or transected sector. Our results demonstrate that pathways within or beneath the suprasylvian gyrus sustain the synchronization of the slow oscillation between cortical sites. As the loss of long-range coherence was not permanent, intergyral paths and/or corticothalamocortical loops may exert compensatory functions after the disconnection of intrasuprasylvian synaptic linkages. PMID- 7790932 TI - Negative feedback neuroendocrine control of the inflammatory response in rats. AB - We describe that an ongoing inflammatory response at one site (produced by complete Freund's adjuvant injection in the hindpaw) produces a negative feedback inhibition on plasma extravasation, produced by perfusion of the inflammatory mediator, bradykinin (160 nM), at a second site (the knee joint). This negative feedback process is abolished in rats that have been neonatally treated with capsaicin to deplete most of their unmyelinated primary afferent fibers, which suggests that this negative feedback process is mediated by activation of primary afferent fibers. Electrical stimulation of the hindpaw at intensities that excite C-fibers also inhibited bradykinin-induced plasma extravasation. Stimulation at intensities that only excite A-fibers had no effect on bradykinin-induced plasma extravasation. Platelet activating factor-induced plasma extravasation, which is not dependent on the innervation of the joint, was not inhibited by stimulation of C-fibers from the hindpaw. Acute surgical interruption of the lumbar sympathetic outflow to the hind limb (the paravertebral ganglia between L2 and L4) did not attenuate the depression of bradykinin-induced plasma extravasation produced by C-fiber stimulation. This indicates that the depression is not mediated by activity in the sympathetic outflow. Transection of the spinal cord, hypophysectomy, inhibition of corticosterone synthesis, and adrenalectomy (but not adrenal medullectomy) all prevented the inhibition of BK-induced plasma extravasation by electrical simulation, indicating that the negative feedback inhibition on plasma extravasation is dependent on an intact neuraxis and an intact hypothalamic-pituitary-adrenocortical axis. In summary, our data demonstrate a negative feedback inhibition of an inflammatory process, which is elicited by stimulation of C-fiber afferents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790934 TI - How to access images on the Internet. PMID- 7790935 TI - Using PET scans to probe the human mind, researchers have been uncovering new ways to understand intelligence as well as differences in the way men and women think. Are these true breakthroughs or junk science? PMID- 7790933 TI - Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. AB - The effects of afferent input and N-methyl-D-aspartate (NMDA) receptor activation on neurogenesis were examined in an intact system, the rat dentate gyrus, where neurons are naturally born in the adult. In the adult dentate gyrus, activation of NMDA receptors rapidly decreased the number of cells synthesizing DNA, whereas blockade of NMDA receptors rapidly increased the number of cells in the S phase identified with 3H-thymidine. Acute treatment with NMDA receptor antagonists increased the birth of neurons and increased the overall density of neurons in the granule cell layer. Lesion of the entorhinal cortex, the main excitatory afferent population to the granule neurons, also increased the birth of cells in the dentate gyrus. These results suggest that adult neurogenesis in the dentate gyrus of the rat is altered by afferent input, via NMDA receptors, and may be regulated naturally by endogenous excitatory amino acids. PMID- 7790936 TI - Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. AB - The main objective of this study was to determine patterns of regional brain metabolic activity utilizing high-resolution PET in normal healthy volunteers and variations in different age groups. METHODS: High-resolution [18F]FDG PET images of the entire brain were obtained in 120 healthy normal volunteers (64 men, 56 women), age range from 19 to 79 yr. Each anatomic region was assessed using a qualitative rating scale with a score ranging from 1 to 6 (1 = definitely normal and 6 = definitely abnormal). Local metabolic activity was also estimated as showing increased (+) or decreased (-) compared to normal (0) states. RESULTS: The most consistent finding in normal aging was decreased cortical metabolism, particularly in the frontal lobes. Temporal, parietal and occipital lobe metabolism varied considerably among subjects within the same age group as well as over decades. Basal ganglia, hippocampal area, thalami, cerebellum, posterior cingulate gyrus and visual cortex remained metabolically unchanged with advancing age. CONCLUSION: These data indicate that qualitative interpretation of FDG-PET images allows accurate assessment of regional metabolic activity of the brain in normal subjects similar to those described with quantitative techniques. Adequate knowledge of normal variations and changes related to normal aging is necessary for optimal assessment of pathologic states. PMID- 7790937 TI - Technetium-99m-HMPAO SPECT imaging of cerebral blood flow during REM sleep in narcoleptics. AB - This study was performed to demonstrate global and regional cerebral blood flow (rCBF) changes during rapid eye movement (REM) sleep in six patients with narcolepsy using SPECT and 99mTc-HMPAO. METHODS: Global and hemispheric HMPAO uptake as well as regional (RI) and asymmetry indices were estimated and compared between polysomnographically verified sleep onset (SO)REM and wakefulness. RESULTS: The estimated global HMPAO uptake did not differ between the two conditions indicating a similar overall cortical activity. During (SO)REM sleep, hemispheric HMPAO uptake as well as calculated RI, especially in the supratemporal plane, were significantly higher on the right side than contralateral. This indicates an initially right-sided cerebral activation and a special involvement of the right, nondominant hemisphere during dreaming which is responsible for visual-spatial perceptions. Furthermore, increased RI in superior parietal regions during sleep were evident and were explained by an activation of associative areas. In thalamic regions, decreased RI were found during sleep, which may reflect thalamic dysfunction. CONCLUSION: A definite assignment of these CBF alterations to (SO)REM sleep might be problematic because of unstable boundaries between sleep stages in narcolepsy. On the other hand, specificity of such CBF changes for narcolepsy requires further study. PMID- 7790938 TI - Functional deficits in autistic disorder: characterization by technetium-99m HMPAO and SPECT. AB - Autistic disorder is an early and severe developmental disorder characterized by deficits in verbal and nonverbal language, social skills, cognitive functioning and an abnormal repertoire of behaviors. Current research, however, has failed to identify the neurobiological mechanisms that underlie autism or those cortical brain regions, if any, that are abnormal. METHODS: We examined regional cerebral blood flow (rCBF) in six young, severely autistic patients. High-resolution brain SPECT with 99mTc-HMPAO was performed while five of the six patients were under general anesthesia. The scans reflected the subjects' rCBF in their usual alert behavioral state, since the tracer was injected at least 15 min prior to anesthesia and is rapidly extracted and fixed in the brain. A computer-automated cortical region of interest (ROI) generator was used to define 12 annular cortical regions (region 1 = left frontal, clockwise to region 12 = right frontal) for count data acquisition. The ratio of average counts in each ROI to whole-slice counts for the autistic patients was compared to age-matched controls using repeated measures (splt-plot) ANOVA statistical analysis for three representative brain levels. RESULTS: In the autistic patients, cortical regions 3, 4, and 10 were abnormally low at the cortical level canthomeatal (CM) + 3.5 cm. At level CM + 5.5 cm, regions 3, 4, 5 and 10 were abnormally low, and at level CM + 7.5 cm, regions 7 and 9 were also abnormally low. These regions correspond to abnormally low rCBF values located predominately in the temporal and parietal lobes, with the left cerebral hemisphere showing greater rCBF abnormalities than the right. CONCLUSION: Our findings suggest that the temporal and parietal lobes have abnormal rCBF in autism. HMPAO brain SPECT in combination with general anesthesia is particularly useful for imaging severely noncompliant patients. PMID- 7790939 TI - High-resolution SPECT to assess hippocampal perfusion in neuropsychiatric diseases. AB - The purpose of this study is to clarify the changes of hippocampal perfusion in neuropsychiatric diseases, including dementia, compared with control subjects, and to correlate hippocampal perfusion with the dementia rating scale and the severity of memory disturbance in patients with these diseases. METHODS: A total of 45 right-handed patients were investigated (13 with dementia of Alzheimer type, 6 with multi-infarct dementia, 4 with progressive dementia with motor neuron disease (MND), 3 with transient global amnesia, 5 with other diseases and 14 control subjects). Regional cerebral blood flow (rCBF) in the parietal cortex and hippocampus was evaluated by high-resolution SPECT technique with HMPAO in all subjects. RESULTS: The rCBF measurements in the bilateral parietal cortices and hippocampus were lower in dementia of Alzheimer type and multi-infarct dementia patients than in controls. Hypoperfusion in the hippocampus was a more sensitive marker than hypoperfusion in the parietal cortex in diagnosing dementia of Alzheimer type. Hippocampal hypoperfusion was observed in demented patients regardless of etiology and in patients having memory disturbance without dementia, such as transient global amnesia. Finally, hippocampal hypoperfusion reflected the severity of dementia and memory disturbance regardless of etiology. CONCLUSION: The rCBF image with high-resolution SPECT system may be useful in assessing the extent of dementia and memory disturbance in patients with neuropsychiatric diseases. PMID- 7790940 TI - Brain SPECT evaluation of the visual cortex in amblyopia. AB - In amblyopia, the number of visual cortical neurons are reduced and abnormal or absent sensitivity to retinal light stimulation of the amblyopic eye is demonstrated. Ten amblyopic patients were studied to evaluate the response of the visual cortex to visual stimulation. METHODS: All patients with unilateral amblyopia received 500-550 MBq 99mTc-HMPAO during visual stimulation. Strobe light flashing was used as the stimulus for five patients and a checkerboard pattern reversal was used in the other five patients, closing one eye. For both groups a 2-Hz frequency was used. One week later, the same procedure was repeated with the opposite eye closed. SPECT images were reconstructed with prefiltering techniques and sliced along the orbitomeatal line. RESULTS: For all patients, the amblyopic eye demonstrated less radioactivity in the visual cortex than in the normal eye. The mean cerebral-to-cerebellar ratios were 0.95 +/- 0.05 and 1.09 +/ 0.07 for amblyopic and normal eyes, respectively (p < 0.0001). CONCLUSION: Visual cortex response of the amblyopic eye to light stimulation was severely reduced when compared to the normal eye. PMID- 7790941 TI - Age-related decline in striatal dopamine transporter binding with iodine-123-beta CITSPECT. AB - The effect of age on human striatal dopamine (DA) transporters was investigated with SPECT using the ligand [123I]2 beta-carbomethoxy-3 beta-(4 iodophenyl)tropane ([123I]beta-CIT). METHODS: Iodine-123-beta-CIT binding in the striatum was examined in 28 healthy human subjects (14 men, 14 women) who ranged in age from 18 to 83 yr. Following injection with [123I]beta-CIT (mean +/- s.d. = 9.9 +/- 1.2 mCi), subjects were scanned with the brain-dedicated CERASPECT camera. A reconstructed transaxial slice 13.3-mm thick at the level of maximal striatal activity was used to determine tracer uptake in striatal and occipital regions of interest. The stability of regional uptake on Day 2 (approximately 18 24 hr postinjection) permitted estimation of the specific-to-nondisplaceable equilibrium partition coefficient: V3", calculated as (striatal- occipital)/occipital uptake at equilibrium. RESULTS: Values of V3" ranged from 3.6 to 11.4 for this sample (6.7 +/- 1.9). V3" showed a significant inverse correlation with age (r = -0.73, n = 28, p < 0.0001). Linear regression analysis revealed that V3" declined by 51% over the age range studied or approximately 8% per decade. CONCLUSION: These findings confirm postmortem reports of dopamine transporter loss with aging. In vivo methodologies may permit the age-related degeneration of dopamine nerve terminals to be studied in relation to the cognitive and motor deficits that occur in normal aging. PMID- 7790942 TI - SPECT imaging of striatal dopamine release after amphetamine challenge. AB - This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sulfate (d amphetamine) challenge testing. METHODS: A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subjects first underwent a controlled experiment to demonstrate that stable levels of striatal and occipital activities could be maintained from 150 to 420 min during programmed infusion of the tracer. Next, seven subjects underwent the experiment with d-amphetamine. The experimental conditions were identical except that 0.3 mg/kg amphetamine was injected intravenously at 240 min. The behavioral effects of d-amphetamine were measured by self-rating on the following analog scales: euphoria, alertness, restlessness and anxiety. RESULTS: The d-amphetamine injection induced a 15% +/- 4% (mean +/- s.d.) decrease in D2 receptor availability, measured as the specific to-nonspecific equilibrium partition coefficient (V3"). The d-amphetamine injection induced marked increase in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availability measured with SPECT. In contrast, the anxiety response was milder and not correlated with the decrease in D2 availability. CONCLUSION: These studies demonstrate the feasibility of using [123I]IBZM programmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correlates of emotions. PMID- 7790943 TI - SPECT imaging of dopamine D2 receptors with 2'-iodospiperone. AB - SPECT imaging of dopamine D2 receptors was performed using 123I-labeled 2' iodospiperone (2'-ISP). METHODS: Iodine-123-2'-ISP was administered to 12 normal subjects. Serial SPECT scans were obtained in six normal subjects for kinetic studies and static SPECT images were obtained in four normal subjects. Two additional normal subjects had serial whole-body imaging to calculate radiation dosimetry. RESULTS: Serial SPECT scans demonstrated rapid initial brain uptake followed by gradual washout from the cerebral cortex and cerebellum, while the activity in the basal ganglia was stable for 2 hr and gradually decreased thereafter. There was fast clearance of blood activity with rapid conversion of 2'-ISP to the hydrophilic metabolites. The basal ganglia-to-frontal cortex ratio increased with time and plateaued between 2 and 4 hr postinjection. The basal ganglia-to-frontal cortex ratio obtained during this period demonstrated an age dependent decrease similar to other D2 ligands. CONCLUSION: 2'-ISP can be used for mapping dopamine D2 receptors in human brain with SPECT. The relatively high background activity, however, suggests that further modification of the compound may be needed prior to widespread clinical use. PMID- 7790944 TI - Iodine-123-IBF SPECT evaluation of extrapyramidal diseases. AB - Iodine-123-IBF is a dopaminergic antagonist suitable for SPECT imaging of D2 receptors. Initial animal studies demonstrated that its affinity for D2 receptors is approximately four times that of the commonly used SPECT D2 ligand [123I]IBZM. In this study we investigated whether this higher affinity would lead to an improved accuracy in differentiating between various extrapyramidal diseases. METHODS: SPECT imaging was performed in 17 patients with idiopathic Parkinson's syndrome (IPS); 4 patients with progressive supranuclear palsy (PSP), 2 patients with multiple system atrophy (MSA) and 7 age-matched control subjects. SPECT imaging was performed 5, 60, 120 and 180 min following intravenous bolus injection of 150-250 MBq of [123I]IBF. The ratio of ligand uptake in the basal ganglia and frontal cortex was determined as a measure of receptor status. RESULTS: In PSP and MSA patients, the basal ganglia-to-frontal cortex ratio reached a plateau at 2 hr; in the control subjects and the IPS patients the ratio was steadily increasing. At 3 hr the basal ganglia-to-frontal cortex ratio was 2.66 +/- 0.29 (control subjects), 3.01 +/- 0.41 (IPS), 2.09 +/- 0.22 (PSP) and 2.10 (MSA). In the IPS patients with predominantly one-sided symptoms, the striatum contralateral to symptoms showed a tendency towards relatively increased ligand uptake. Despite the higher affinity of IBF for the D2 receptor compared to IBZM, the separation of individual PSP and MSA patients from the control subjects was not as clear cut as reported for IBZM due to a relatively high variation in the control subjects. We hypothesize that the latter is due to imaging in nonequilibrium conditions. CONCLUSION: The data suggest that IBF-SPECT can help in discriminating extrapyramidal disease. The accuracy might be improved by an administration protocol that allows imaging in "true equilibrium" conditions, such as a bolus injection followed by a constant infusion. PMID- 7790945 TI - Simple quantification of benzodiazepine receptor binding and ligand transport using iodine-123-iomazenil and two SPECT scans. AB - The feasibility of simplified procedures for the quantification of benzodiazepine receptor binding using [123I]iomazenil and SPECT was assessed. METHODS: Six normal male volunteers were studied. Following intravenous injection of 111 MBq [123I]iomazenil, serial dynamic SPECT scanning was performed for 120 min and the concentration of lipophilic compounds in the arterial plasma was determined by chloroform extraction. Kinetic parameters were estimated by a curve-fitting procedure using the following four models: three-compartment, four-parameter (K1 k4) (3C4P), three-compartment, three-parameter (fixed K1/k2) (3C3P), three compartment, two-parameter (fixed K1/k2 and k4) (3C2P) and two-compartment, two parameter (K1 and k2) (2C2P). Kinetic parameters were also calculated by a table look-up procedure with 3C2P using only two SPECT data acquisitions. Parametric images were generated based on the same procedure. RESULTS: In all models, the curve-fitting procedure gave similar outcomes for ligand transport (K1) and receptor density parameters (i.e., binding potential or distribution volume). The 3C4P parameters showed significant correlation between k2 and k3, while 3C3P did not show such a correlation, suggesting the stability of 3C3P. The 3C2P provided parameters essentially identical to those with the 3C3P, indicating the suitability of this model, while 2C2P gave similar distribution volume but obviously low K1. CONCLUSION: Table look-up procedures based on the 3C2P model permit quantification of benzodiazepine receptor binding using [123I]iomazenil with two SPECT scans. This method may be of clinical value in the diagnosis of various diseases. PMID- 7790946 TI - Improved regional cerebral blood flow in chronic cocaine polydrug users treated with buprenorphine. AB - Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. METHODS: Fifteen cocaine- and heroin-dependent men were studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. RESULTS: Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. CONCLUSION: Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men. PMID- 7790947 TI - Lateralized differences in iodine-123-IBZM uptake in the basal ganglia in asymmetric Parkinson's disease. AB - We used equilibrium analysis of SPECT data from patients with asymmetric Parkinson's disease to determine if lateralized differences in the striatal uptake of [123I]IBZM correlate with asymmetry in clinical findings and, by inference, with lateralized differences in the concentration of extracellular dopamine. METHODS: Twelve patients with asymmetric clinical signs of idiopathic Parkinson's disease were injected with a bolus of [123I]IBZM, and multiple SPECT scans recorded the time course of radioligand uptake. The time integral method was used to estimate peak specific binding, so that a ratio of specific-to nonspecific binding in the left and right striatum of each subject at equilibrium could be determined. Nine patients also had 99mTc-HMPAO SPECT scans which were examined for evidence of blood flow asymmetries. RESULTS: Paired t-tests comparing [123I]IBZM uptake revealed significantly greater (mean = 7.3%) availability of dopamine-D2 receptors in the basal ganglia contralateral to maximal clinical signs. Differences in receptor availability correlated significantly with differences in every measure of the clinical assessment. No significant differences in regional cerebral blood flow between the two sides were observed with 99mTc-HMPAO. CONCLUSION: These results demonstrate the ability of [123I]IBZM SPECT to reveal clinically meaningful variations in striatal dopamine receptor availability in patients with asymmetric Parkinson's disease. The equilibrium analysis technique used to determine these findings is a simple and robust method of measuring relative receptor availability and may be useful in studying other illnesses where dysfunction of dopaminergic neurotransmission is suspected. PMID- 7790948 TI - Regional striatal DOPA transport and decarboxylase activity in Parkinson's disease. AB - METHODS: We measured blood-brain barrier transport and decarboxylation of 6 [18F]fluoro-L-DOPA (FDOPA) using PET in patients with Parkinson's disease (n = 7, 57 +/- 7 yr) and age-matched control subjects (n = 7, 60 +/- 6 yr). To visually present regional changes of FDOPA uptake in Parkinson's disease, we introduced maps of FDOPA uptake relative to occipital cortex, averaged across control subjects and Parkinson's disease patients in an MRI-based stereotaxic coordinate space. RESULTS: There was no significant changes in the blood-to-brain transport of FDOPA (KD1) in Parkinson's disease. The KD1 values of the head of caudate were lower than those of putamen in both normal subjects and Parkinson's disease patients. In Parkinson's disease, the activity of L-DOPA decarboxylase (DDC) was differentially reduced in subdivisions of striatum. The residual DDC activity was 63% of the control value in the head of caudate nucleus, 54% in the anterior putamen and 39% in the posterior putamen. The DDC activity in frontal and occipital cortices remained unchanged by the disease. Subtraction of averaged FDOPA uptake maps (control minus Parkinson's disease) visualized a spatial pattern of pathological changes in FDOPA uptake common to Parkinson's disease patients. CONCLUSION: The striatal blood-to-brain transport of FDOPA remained unchanged while the DDC activity was differentially reduced within the striatum in Parkinson's disease. We found the FDOPA uptake maps useful in identifying altered patterns of FDOPA metabolism common in Parkinson's disease. PMID- 7790949 TI - Aging effect on neutral amino acid transport at the blood-brain barrier measured with L-[2-18F]-fluorophenylalanine and PET. AB - Neutral amino acids (NAAs) are transported from the blood to the brain using the same carrier system in a competitive fashion. The purpose of this study is to establish a method for evaluating neutral amino acid transport at the blood-brain barrier (BBB) in humans and to examine the aging effect of amino acid transport. METHODS: A dynamic PET study with L-(2-18F)-fluorophenylalanine (18F-Phe) was performed in 14 normal volunteers (age 21-71 yr; mean +/- s.d., age range 48.0 +/ 17.1 yr). By using a two-compartment model analysis and a weighted integration technique, the influx rate constant K1, the efflux rate constant k2 and distribution volume Vd of 18F-Phe were estimated in various brain structures. RESULTS: The value of K1 was inversely correlated with plasma NAA concentration (r = -0.69, p < 0.01). The cerebellum showed the highest value of K1, while the white matter showed the lowest. There was no significant change in K1 during aging. The value of k2 was significantly increased with age. CONCLUSION: No decline of K1 during aging indicated that NAA transport from the blood to the brain is a limiting process of age in amino acid incorporation. Fluorine-18-Phe PET imaging is a feasible method to study NAA transport at the BBB in vivo in humans and can be applied to pathological conditions of the brain. PMID- 7790951 TI - FDG-PET in early infancy: simplified quantification methods to measure cerebral glucose utilization. AB - For further insight into the physiology and pathogenesis of the developing brain, quantification of the cerebral glucose metabolism is needed. Arterial blood sampling or sampling of great volumes of blood is not justified for the purpose of PET studies in children. Therefore, we have developed simplified PET approaches to analyze brain FDG examinations during infancy. METHODS: The study consisted of 18 FDG-PET examinations chosen from our research protocols concerning hypoxicischemic encephalopathy and severe neonatal hypoglycemia. The input function for graphical analysis according to Patlak was derived in two ways: (1) a combined time-activity curve derived from the left ventricular activity concentration (first 7-17 min of the study) and radioactivity concentration in venous whole-blood samples and; (2) activity concentration measured in whole-blood venous blood samples (arterial plasma in one case). As an alternative for semiquantitation, the standardized uptake values (SUV) were calculated and correlated to local cerebral metabolic rates for glucose (LCMRGlc). RESULTS: The influx rate constants (Ki) and LCMRGlc values obtained using the combined curve versus venous curve did not differ statistically (p > 0.05). There was a good correlation between the SUV and LCMRGlc values (r = 0.83, p < 0.001). CONCLUSION: Local cerebral metabolic rates for glucose can be accurately calculated by using the combined curve (left ventricular activity concentration during first 5 min of the study and 2-3 venous whole-blood samples at the end of the study) for even the smallest pediatric patients. When blood samples cannot be obtained, SUV values provide an alternative for estimation of the cerebral glucose uptake and interindividual comparison of the patients. PMID- 7790950 TI - A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. AB - To improve the diagnostic performance of PET as an aid in evaluating patients suspected of having Alzheimer's disease, we developed a fully automated method which generates comprehensive image presentations and objective diagnostic indices. METHODS: Fluorine-18-fluorodeoxyglucose PET image sets were collected from 37 patients with probable Alzheimer's disease (including questionable and mild dementia), 22 normal subjects and 5 patients with cerebrovascular disease. Following stereotactic anatomic standardization, metabolic activity on an individual's PET image set was extracted to a set of predefined surface pixels (three-dimensional stereotactic surface projection, 3D-SSP), which was used in the subsequent analysis. A normal database was created by averaging extracted datasets of the normal subjects. Patients' datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspections. Diagnostic indices were then generated based on averaged Z-scores for the association cortices. RESULTS: Patterns and severities of metabolic reduction in patients with probable Alzheimer's disease were seen in the standard 3D-SSP views of extracted raw data and statistical Z-scores. When discriminating patients with probable Alzheimer's disease from normal subjects, diagnostic indices of the parietal association cortex and unilaterally averaged parietal-temporal-frontal cortex showed sensitivities of 95% and 97%, respectively, with a specificity of 100%. Neither index yielded false-positive results for cerebrovascular disease. CONCLUSION: 3D SSP enables quantitative data extraction and reliable localization of metabolic abnormalities by means of stereotactic coordinates. The proposed method is a promising approach for interpreting functional brain PET scans. PMID- 7790952 TI - Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping. AB - Recent human PET studies with the monoamine oxidase B (MAO B) tracer [11C]L deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl ([11C]L deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity. METHODS: Five normal subjects (43-64 yr) were studied with [11C]L-deprenyl and [11C]L-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems. RESULTS: For both tracers, maximum radioactivity accumulation occurred at about 5 min. For [11C]L-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With [11C]L-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for [11C]L-deprenyl was higher than the plateau for [11C]L-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity. CONCLUSION: This study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration. PMID- 7790954 TI - Cerebral blood flow and perfusion reserve capacity in hemodynamic carotid transient ischemic attacks due to innominate artery stenosis. AB - Ischemia in the carotid artery territory due to atherosclerotic stenosis of the innominate artery is rare. We report a case in which transcranial Doppler ultrasonography (TCD) and SPECT with acetazolamide challenge proved the hemodynamic mechanism. The patient presented with three hypotensive TIAs in the right middle cerebral artery territory. Angiography showed a tight innominate artery stenosis and subclavian steal but no coexistent carotid or vertebrobasilar lesion. SPECT showed disturbed regional blood flow in the middle cerebral artery territory along with an exhausted perfusion reserve capacity. After angioplasty, flow velocities were normal and the perfusion reserve was restored. SPECT should be used to select patients at risk susceptible to benefit from angioplasty. PMID- 7790955 TI - Cortical blindness after correction of symptomatic hyponatremia: dynamic cerebral dysfunction visualized using serial SPECT scanning. AB - A 70-yr-old woman developed cortical blindness after correction of hyponatremia. Regional hyperperfusion was noted on SPECT scans obtained in the acute phase. One month later when symptoms had largely resolved, a repeat examination was normal. This regional hyperperfusion, which was not associated with any apparent structural damage, may have represented either luxury perfusion or a transient increased metabolic requirement of the dysfunctional cortical area. SPECT scanning may be a useful method to study cerebral dysfunction resulting from an osmotic disturbance. PMID- 7790953 TI - PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease. AB - The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/ 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains. PMID- 7790956 TI - Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. AB - D2 dopamine receptors in extrastriatal brain regions are of central interest for research in schizophrenia and antipsychotic drugs. This article reports the development of [11C]FLB 457 for PET examination of extrastriatal D2 dopamine receptors. METHODS: Carbon-11-FLB 457 was prepared by O-methylation of FLB 604 (2 hydroxy precursor) with [11C]methyl iodide. Total radiochemical yield was 25%-35% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was about 1300 Ci/mmole (48 GBq/mumole). RESULTS: FLB 457 bound with high affinity to D2 and D3 dopamine receptors, whereas binding to other putative central receptors was negligible. PET studies in Cynomolgus monkeys demonstrated 15 times higher accumulation of radioactivity in the striatum than in the cerebellum after 60 min. Uptake in the thalamus and neocortex, extrastriatal regions with a low density of D2 dopamine receptors, was, respectively, 4 and 2.5 times higher than in the cerebellum. Radioactivity was displaced by raclopride and haloperidol which confirms the selectivity and reversibility of [11C]FLB 457 binding to D2 dopamine receptors in vivo in the striatum, thalamus and neocortex. CONCLUSION: Carbon-11-FLB 457 should be a useful PET ligand for quantitative examination of D2 dopamine receptors in extrastriatal regions in the human brain. PMID- 7790957 TI - In vitro and in vivo characterization of R(+)-FIDA2: a dopamine D2-like imaging agent. AB - R(+)-FIDA2, (R)-(+)-2,3-dimethoxy-5-iodo-N-[(1-(4'-fluorobenzyl)-2-pyrrolid iny l)- methyl]benzamide, is a new dopamine D2-like receptor imaging agent that can be labeled with either 123I or 18F for SPECT or PET imaging. The purpose of this study was to characterize its in vitro and in vivo binding properties. METHODS: In vitro binding studies using [125I]R(+)-FIDA2 were performed in Sf9 cells expressing dopamine D2 or D3 receptors and in rat basal forebrain homogenates, which contain a high density of dopamine D2-like receptors. A series of in vivo SPECT imaging studies in nonhuman primates (cynomologous monkeys) were performed by intravenously injecting 7.1 +/- 1.0 mCi of [123I]R(+)-FIDA2. At least one control study and one displacement experiment, in which a cold compound was injected intravenously 90 min after tracer injection, was performed in each monkey. Data were acquired in 10-min frames for 180 min, and the activity in regions of interest (basal ganglia and cerebellum) were plotted versus time. RESULTS: Iodine-125-R(+)-FIDA2 displayed Kd values for D2 and D3 receptor subtypes expressed in Sf9 cells of 0.11 and 0.04 nM, respectively. As expected, SPECT images of monkey brain (transaxial sections, 2 mm) showed that the radioactivity was localized in the area of the basal ganglia and reached peak concentrations in 11.5 +/- 5.8 min postinjection. An injection of R(+)7-OH-PIPAT, a new ligand that is selective for dopamine D3 receptors and the high affinity state of dopamine D2 receptors, did not show significant displacement of [123I]R(+)-FIDA2 binding in the basal ganglia. CONCLUSION: These studies indicate that R(+)-FIDA2 may be a useful ligand for in vitro pharmacological characterization and in vivo imaging of CNS dopamine D2-like receptors. PMID- 7790958 TI - Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: a PET study. AB - We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. METHODS: PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). RESULTS: At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine. CONCLUSION: At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter. PMID- 7790959 TI - Functional studies in substance abuse: imaging and beyond. PMID- 7790960 TI - High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. AB - Fluorine-18-2-deoxy-2-fluoro-D-glucose ([18F]FDG) uptake and distribution in an experimentally induced inflammatory tissue were investigated. METHODS: Rats were subcutaneously inoculated with turpentine oil to induce inflammation and used for tissue distribution studies and autoradiography. RESULTS: Time course study of [18F]FDG tissue distribution showed that the uptake in inflammatory tissue increased gradually until 60 min and then decreased. A longitudinal study of [18F]FDG tissue distribution showed that the uptake increased progressively to a peak 4 days after inoculation and then decreased. On the fourth day postinoculation, a section of inflammatory tissue showed characteristic changes of chronic inflammation. Macro- and micro-autoradiography showed a high density of silver grains in the abscess wall consisting of an inflammatory cell layer and granulation tissue. Grain counting on micro-autoradiography of the abscess wall showed that the highest grain density was found in the marginal zone of young fibroblasts, endothelial cells of vessels and phagocytes of neutrophils and macrophages, followed by that in the neutrophil layer and granulation tissue. CONCLUSION: Our results indicate that [18F]FDG PET may be useful in detecting and monitoring chronic inflammatory processes. PMID- 7790961 TI - A method for coregistration of PET and MR brain images. AB - Combining MRI morphological data with functional PET data offers significant advantages in research as well as in many clinical situations. Automatic methods are needed, however, to coregister the data from the two modalities. METHODS: Simulated PET images were created by simple and automatic segmentation of MR images followed by the assignment of different uptake values to various tissue types. The simulated PET images were registered to actual PET images using a pixel-by-pixel, PET-PET registration method. The transformation matrix was then applied to the MR images. The method was used to register MRI data to PET transmission scans and emission scans obtained with FDG, nomifensine and raclopride. Validation was performed by comparing the results to those obtained by matching internal points manually defined in both volumes. RESULTS: Emission and transmission PET images were successfully registered to MR data. Comparison to the manual method indicated a registration accuracy on the order of 1-2 mm in each direction. No difference in accuracy between the different tracers was found. The error sensitivity for the method's assumptions seemed to be sufficiently low to allow complete automation of the method. CONCLUSION: We present a rapid, robust and fully automated method to register PET and MR brain images with sufficient accuracy for most clinical applications. PMID- 7790962 TI - Dosimetry of iodine-123-epidepride: a dopamine D2 receptor ligand. AB - Substituted benzamides have been shown to have very high affinity and specificity for the dopamine D2 receptor. One of these is radiolabeled epidepride, an iodine substituted benzamide currently under evaluation as a SPECT imaging agent. Detailed estimates of the radiation absorbed dose to 26 organs and the whole body from [123I]epidepride have been calculated. METHODS: The dosimetry calculations use a combination of in vivo uptake and biodistribution data from one rhesus monkey and seven humans to estimate residence times in eight organs. The computer program MIRDOSE2 was used to calculate the dosimetry. RESULTS: Results indicate that 75% of the radioactivity is cleared through the urinary tract while the remaining radioactivity clears through the gallbladder and intestinal tract. The radiation absorbed dose can be minimized by administering a high lipid content meal 1.5 hr postinjection to empty the gallbladder and by giving large volumes of fluids throughout the study to induce increased urinary output. CONCLUSION: By emptying the gallbladder and urinary bladder, the lower large intestine becomes the critical organ, 0.102 mGy/MBq (0.38 rad/mCi) followed by the upper large intestine, 0.092 mGy/MBq (0.34 rad/mCi). The effective dose equivalent is 0.025 mSv/MBq (0.092 rem/mCi). PMID- 7790964 TI - Human dosimetry and biodistribution of iodine-123-iododexetimide: a SPECT imaging agent for cholinergic muscarinic neuroreceptors. AB - Iodine-123-iododexetimide (IDEX) has recently been used for SPECT imaging of muscarinic cholinergic neuroreceptors (mAChR) in humans. We report the human radiation dosimetry, whole-body and normal cerebral distribution of IDEX. METHODS: Serial whole-body planar and brain SPECT scans were performed over 24 hr in four normal subjects. Organ activity was calculated from attenuation-corrected geometric mean counts from ROIs drawn over visible organs. Thigh activity was used for background subtraction. Organ absorbed doses and effective dose were calculated using the MIRD schema. Brain SPECT was performed 6 hr postinjection in ten normal subjects. ROIs placed over cortical and subcortical structures were used to determine brain distribution. RESULTS: The effective dose was 24.7 microSv/MBq. An average of 54% of IDEX remained in the body background. Decay corrected brain uptake was 6.9% of injected dose at 1 hr, 8.6% at 6 hr and 8.1% at 24 hr. Regional brain distribution showed high uptake in striatum and cortex with low activity in thalamus and cerebellum. At 6 hr, activity relative to striatum was 70% for frontal and parietal cortex, 102% for occipital cortex, 54% for thalamus and 11% for cerebellum. CONCLUSION: Iodine-123-IDEX produced high quality SPECT images with activity at 6 hr reflecting the known distribution of mAChR receptors. The favorable dosimetry of IDEX and high synthetic yield (50% 70%) suggest it to be a suitable agent for clinical studies. PMID- 7790963 TI - Dosimetry of a D2/D3 dopamine receptor antagonist that can be used with PET or SPECT. AB - FIDA-2 (R-(+)-2,3-dimethoxy-5-iodo-N-[(1-4'-fluorobenzyl)-2-pyrrolidinyl) methyl] benzamide) is a simultaneously fluorinated and iodinated D2/D3 dopamine receptor antagonist. The purpose of this study was to measure its biodistribution and radiation dosimetry in humans. METHODS: Whole-body emission scans were sequentially acquired in eight healthy volunteers 24-43 hr after the intravenous administration of 101-150 MBq 123I FIDA-2. Regions of interest (ROIs) were placed on the initial set of conjugate emission images and transposed as a single set onto all the other scans without manipulating any of the regions for solid organs independently. The counts in each ROI were corrected for attenuation with transmission scans and compared to the net counts in images of the injection syringe containing the administered dose. The radiation doses were estimated with the MIRD formalism from the residence times for both the 18F- and 123I-labeled ligands. RESULTS: There were no subjective or objective pharmacological effects of the tracer on any of the subjects. The findings showed that the dose-limiting organ for the 123I-labeled product was the thyroid gland in this sample. If the 18F-labeled product had been used, then the urinary bladder would have received 0.086 mGy/MBq (0.32 rads/mCi) and become the dose-limiting organ. The effective dose equivalents were 0.025 mSv/MBq (0.092 rem/mCi) for both the 123I- and the 18F-labeled versions of the tracer. CONCLUSION: The data suggest that FIDA-2 can be used to produce relatively high contrast images of the D2/D3 dopaminergic system with substantially less than the maximum allowable radiation dose for research volunteers. PMID- 7790966 TI - Ward Valley waste site poised to get green light. PMID- 7790965 TI - Evaluation of a double-injection method for sequential measurement of cerebral blood flow with iodine-123-iodoamphetamine. AB - To test the feasibility of applying N-isopropyl-[123I]p-iodoamphetamine (IMP) for sequential measurements of regional cerebral blood flow (rCBF) with injection of two separate doses in a single procedure, kinetic analysis based on a two compartment model was done using dynamic SPECT data. A microsphere model analysis without consideration of IMP washout from the brain was also tested for clinical application. METHODS: A dynamic SPECT scan consisting of fifty 1-min scans was obtained on 15 patients using a three-head rotating gamma camera with two separate doses of IMP (111 MBq each) at the beginning and 25 min after scan initiation. The reproducibility of two resting rCBF scans was tested in six patients and the cerebrovascular response shown by increased rCBF with acetazolamide (1 g) was assessed in nine patients. RESULTS: Two-compartment model analysis showed excellent reproducibility of resting rCBF scans and significantly different cerebrovascular reactivity to acetazolamide between areas with and without ischemia. Microsphere model analysis showed smaller values in the first rCBF image by 3% and in the second by 10%, resulting in lower values for cerebrovascular reactivity. The difference in cerebrovascular reactivity between ischemic and nonischemic areas, however, is highly significant. CONCLUSION: The double-injection method for IMP is feasible for two sequential rCBF measurements in a single procedure and is applicable for acetazolamide challenge. Simple microsphere model analysis, as well as a two-compartment model analysis, provide reliable assessment for cerebrovascular reactivity despite the complex dynamics of IMP and are feasible for clinical application. PMID- 7790967 TI - Scenes from the Oklahoma City bombing. PMID- 7790969 TI - Reawakening thinking: is traditional pedagogy nearing completion? PMID- 7790968 TI - From the past to the future: awarding nuclear medicine innovators. PMID- 7790970 TI - What does it mean to be well taught? A hermeneutic course evaluation. AB - Evaluating courses is an ongoing part of nursing education. With the adoption of innovative approaches to nursing curricula, there is an increasing need for congruent forms of evaluation. This paper explores the character of a hermeneutic course evaluation within a practice-driven, phenomenological approach to a 4-year baccalaureate curriculum. An interpretation of evaluation data from 2 years of an introduction to nursing course reveals a distinction between learning and being well taught. The article focuses on the theme "being well taught as experiencing structure," and the importance of teaching practices that achieve a balance between specificity and flexibility. It is evident that evaluations that focus on understanding and uncovering what is usually taken for granted have the capacity not only to indicate what works and does not work in a course, but also to depict a course's phenomenological nature and to illuminate the transformative power of narrative as it situates and extends learning. PMID- 7790972 TI - Lessons from literature: caring, interpretation, and dialogue. AB - There can be little doubt that nursing, like other arts and sciences, is experiencing an "interpretive turn" (Hiley, Bohman, & Shusterman, 1991). As part of this more global "turn," the curriculum revolution has spurred nurse educators to critically examine their schools, curricula, and everyday practices as teachers and propose alternative pedagogies where appropriate. I argue that what is now being developed as nursing humanities is a valuable approach to interpretive pedagogy which challenges, stimulates, integrates, and develops students' thinking and understanding of the lived experience of patients/clients in ways that more traditional scientific and behaviorist approaches to nursing education are unable to do. In creating courses or learning experiences using nursing humanities, it is essential to attend to both content and pedagogical approach as being inseparable. Ignoring the former will produce no more than a pleasant chat, while ignoring the latter will result in mere "metaphor counting" or rote learning of "what the book, story, or poem means." Nurse educators have used literature to help illuminate health and illness issues in the past, but unfortunately, this has been viewed as an essentially marginal approach. While novels, stories, poems, and other literature can certainly be used in almost any nursing class, I believe that nursing humanities is such a rich seam of pedagogical and critical possibility that it merits development of specific courses and options within all of our nursing courses and programs. PMID- 7790971 TI - Narrative pedagogy: rethinking nursing education. AB - Narrative pedagogy is an interpretive approach to teaching and learning that is being used to foster educational reform. As it pertains to nursing education, narrative pedagogy is an approach to thinking about teaching and learning that evolves from the lived experiences of teachers, clinicians, and students. In this article, the author reviews the philosophical underpinnings of narrative pedagogy, provides examples of how narrative pedagogy can be used to rethink the teaching of nursing knowledge and practice, and discusses the strengths and limitations of narrative pedagogy as an alternative approach to teaching and learning. PMID- 7790974 TI - Cooperative learning and feminist pedagogy--a model for classroom instruction in nursing education. AB - This article reports on a research study conducted as part of a doctoral dissertation on the development of a cooperative learning teaching model in nursing education. The subjects for the study were a convenience sample of registered nurses who were pursuing a baccalaureate degree in nursing at an urban university. Principles of feminist pedagogy were incorporated as part of the cooperative learning model. The teacher/researcher taught two sections of the same course and, through the use of action research, developed a model for using cooperative learning strategies as the primary teaching modality. End of class and end of semester evaluations provided feedback that suggested that this was an exciting and effective alternative to traditional classroom teaching. PMID- 7790975 TI - Fostering dialogical community through a learning experience. AB - Dialogue and community are two common foci of the recent nursing education literature. The author came to a new understanding of these concepts while teaching a capstone seminar course for registered nurses who were obtaining a baccalaureate degree. In this paper, this transformation is discussed in the context of one particular learning experience for the capstone course. The philosophical basis for fostering dialogical community through this learning experience is explained. The experience is described, and students' comments about the experience are cited. Finally, conclusions drawn as a result of the experience are compared to the themes of dialogue and community in the recent nursing education literature. PMID- 7790973 TI - An interpretive analysis of precepting an unsafe student. AB - Precepting students during their senior practicum is often viewed as an opportunity to nurture the next generation of nurses. However, when the student has only marginally passed courses or clinical experiences, precepting may become a difficult and challenging process. Little is known about how preceptors teach students and even less is known about precepting unsafe students. The purpose of this article is to describe a preceptor's journey through a difficult senior practicum experience. A hermeneutic analysis of the preceptor's journal revealed two themes important in precepting the unsafe student: knowing the student and creating possibilities for success. Two aspects of knowing the student included watchful listening and assessing dangerousness. These themes are described and the dilemma of bringing an unsafe nurse into the profession is discussed. PMID- 7790976 TI - Clinical learning experiences and professional nurse caring: a critical phenomenological study of female baccalaureate nursing students. AB - The purpose of this critical phenomenological study was to discover, describe, and analyze how nursing students learn professional nurse caring in the clinical context of nursing education. In this article, I report on interviews from 18 female baccalaureate nursing students, 17 of whom are European American and one of whom is African American. Participants in this study narrated their stories about learning caring by first describing their understanding of how they created caring with patients. After uncovering the layers of their patient care interactions, they were then able to answer the research question of how they learned caring in clinical. Because participants' interactions with patients were the context for the development of their understanding of caring, I identify the relational theme of caring and interacting with patients as the central focal point for narrating stories about caring. From the data analysis, I report two constitutive patterns: the first, creative caring, contains seven themes, and the second, learning caring, contains five themes. Findings from this research are summarized as "embodied caring knowledge." This research has implications for nursing faculty, students, and practitioners who are interested in enhancing their understanding of living and learning caring within nursing. PMID- 7790977 TI - Feminist pedagogy: developing creative approaches for teaching students of nursing. PMID- 7790978 TI - Preferences for cardiopulmonary resuscitation: physician-patient agreement and hospital resource use. The SUPPORT Investigators. AB - OBJECTIVE: To describe the association between hospital resource utilization and physicians' knowledge of patient preferences for cardiopulmonary resuscitation (CPR) among seriously ill hospitalized adult patients. DESIGN: Prospective cohort study. SETTING: Five U.S. academic medical center, 1989-1991. PATIENTS: A sample of 2,636 patients with self- or surrogate interviews and matching physician interviews describing patient preferences for CPR, from a cohort of 4,301 patients with life-threatening illnesses enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). MEASURES: Patient, surrogate, and physician reports of preferences for resuscitation, and resource use derived from the Therapeutic Intensity Scoring System and hospital length of stay, converted into 1990 dollars. RESULTS: Nearly one-third of the patients preferred to forego resuscitation. Of the 2,636 paired physician-patient answers, nearly one-third did not agree about preferences for resuscitation. The physicians' views of the patients' preferences and those preferences themselves were both associated with resource use. Standardized adjusted hospital resource consumption, expressed as average cost in dollars during the enrollment hospitalization, was lowest when the physician agreed with the patient preference for a do-not-resuscitate order ($20,527), and highest when the patient did not have a preference and the physician believed the patient wanted resuscitation in the case of a cardiopulmonary arrest ($34,829). Hospital resource use was intermediate when patient-physician pairs evidenced either lack of agreement or communication, or awareness of options about resuscitation. CONCLUSIONS: Both physician and patient preferences for CPR influence total hospital resource consumption. Physician misunderstanding of patient preferences to forego CPR was associated with increased use of hospital resources, and could have led to a course of care at odds with patients' expressed preferences in the event of cardiac arrest. Increasing physicians' knowledge of patient preferences, and increasing communication to help patients understand that options for medical care that include foregoing resuscitation efforts, might reduce hospital expenditures for the seriously ill. PMID- 7790979 TI - The effect of diagnosing Alzheimer's disease on frequency of physician visits: a case-control study. AB - OBJECTIVE: Two groups of elderly subjects were studied to see whether patterns of visits to physicians changed after one group received the diagnosis of Alzheimer's disease. DESIGN: Case-control study. SETTING: Health maintenance organization (HMO). PATIENTS/PARTICIPANTS: Two groups of ambulatory subjects (mean age 77 years) were enrolled from an HMO population for this case-control study: 120 cases had probable Alzheimer's disease diagnosed at enrollment, and another 120 cognitively intact controls with similar comorbidity were enrolled after being frequency-matched for age and gender. Exclusion criteria were nursing home admission and death during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were examined for a four-year period: two years prior to and two years following enrollment and diagnosis. Physician visits declined slightly after enrollment for the persons receiving the diagnosis of Alzheimer's disease [17.5/2 years prior vs 16.5/2 years after (NS)], whereas visits increased over time for the controls [13.7/2 vs 16.3/2 (p < 0.05)], hence the rates were similar after enrollment [16.5 vs 16.3 (NS)]. The proportion of subjects with fewer visits during the period after enrollment was higher among the cases than it was among the controls [54% vs 37%; odds ratio = 2.0 (95% confidence interval = 1.6, 3.1)]. Hospitalizations and emergency department use did not change significantly after enrollment. CONCLUSIONS: Physician visit frequency was high before, then decreased after, demented patients received their diagnosis, approaching the frequency in a control population without dementia. This phenomenon cannot be accounted for by nursing home placement, comorbidity, or mortality. Increased hospitalization and emergency department use did not ensue after diagnosis. PMID- 7790980 TI - A comparison of self-report and chart audit in studying resident physician assessment of cardiac risk factors. AB - OBJECTIVE: To examine the relationship between resident physicians' perceptions of their preventive cardiology practices and a chart audit assessment of their documented services. DESIGN: A criterion standard comparison of two methods used to assess resident physicians' practices: self-report and chart audit. SETTING: Physician ambulatory care in a residency program. PATIENTS AND OTHER PARTICIPANTS: Coronary artery disease (CAD) risk factor assessment was evaluated by self-report for 72 resident physicians and by chart audit of randomly selected records of 544 of their patients who did not have CAD or a debilitating chronic disease during a one-year period. INTERVENTION: Measurements of the residents' perceived CAD risk factor assessment practice by self-report, and chart audit assessments of their recorded care. MAIN OUTCOME: The relationship between self reported and chart audit assessments of CAD risk factors. RESULTS: Chart audit assessment of CAD risk factor management was highly significantly (p < 0.01) lower than self-reported behaviors for evaluation of cigarette smoking, diet, physical activity, stress, plasma cholesterol, blood pressure, and body weight/obesity. CONCLUSIONS: Three different interpretations of these findings are apparent. 1) Physician self-report is a poor tool for the measurement of clinical behavior, and therefore research of physician behavior should not rely solely on self-reported data; 2) physicians' chart recording of their clinical practice is insufficient to reflect actual care; or 3) neither is an accurate measure of actual practice. PMID- 7790981 TI - Relationship between medication errors and adverse drug events. AB - OBJECTIVE: To evaluate the frequency of medication errors using a multidisciplinary approach, to classify these errors by type, and to determine how often medication errors are associated with adverse drug events (ADEs) and potential ADEs. DESIGN: Medication errors were detected using self-report by pharmacists, nurse review of all patient charts, and review of all medication sheets. Incidents that were thought to represent ADEs or potential ADEs were identified through spontaneous reporting from nursing or pharmacy personnel, solicited reporting from nurses, and daily chart review by the study nurse. Incidents were subsequently classified by two independent reviewers as ADEs or potential ADEs. SETTING: Three medical units at an urban tertiary care hospital. PATIENTS: A cohort of 379 consecutive admissions during a 51-day period (1,704 patient-days). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Over the study period, 10,070 medication orders were written, and 530 medications errors were identified (5.3 errors/100 orders), for a mean of 0.3 medication errors per patient-day, or 1.4 per admission. Of the medication errors, 53% involved at least one missing dose of a medication; 15% involved other dose errors, 8% frequency errors, and 5% route errors. During the same period, 25 ADEs and 35 potential ADEs were found. Of the 25 ADEs, five (20%) were associated with medication errors; all were judged preventable. Thus, five of 530 medication errors (0.9%) resulted in ADEs. Physician computer order entry could have prevented 84% of non-missing dose medication errors, 86% of potential ADEs, and 60% of preventable ADEs. CONCLUSIONS: Medication errors are common, although relatively few result in ADEs. However, those that do are preventable, many through physician computer order entry. PMID- 7790983 TI - Medical malpractice reform: the current proposals. PMID- 7790982 TI - When the physician leaves the patient: predictors of satisfaction with the transfer of care in a primary care clinic. AB - OBJECTIVE: To identify independent predictors of patients' satisfaction with transfer of their care from a departing to a new resident physician. DESIGN: A self-administered questionnaire completed by consecutive patients following up after transfer of their care, and by a randomly selected 50% of patients not returning within three months after transfer. SETTING: An internal medicine clinic in a teaching hospital. PATIENTS: Questionnaires were completed by 376 patients: 237 returning to clinic and 139 (91%) of 152 randomly selected patients who had not returned. Mean age of the patients was 65 years, 52% were men, and they had come to the clinic for a median of four years. RESULTS: 57% of the patients were satisfied with the transfer process, 25% were neutral, and 18% expressed frank dissatisfaction. Of nine variables significantly associated with satisfaction by univariate analysis, stepwise multiple regression identified five independent predictors. Personal notification of the patient by the departing physician was the most powerful determinant, explaining 41% of the variability in satisfaction. Other predictors were whether patients believed their physicians had done everything possible to facilitate transfer, whether the departing physician had provided opportunity for discussion of the transfer, whether this discussion was considered sufficient, and patients' impressions of the institution. CONCLUSIONS: Most of the predictors identified can be influenced by physician behavior, suggesting that physicians should personally notify patients of their departure and provide an opportunity for discussion. This could significantly improve patient satisfaction with the transfer process and, as previous studies suggest, translate into greater compliance with medications and follow-up. PMID- 7790985 TI - Confounders of auscultatory blood pressure measurement. AB - The appropriate use of any test requires the clinician to appreciate that test's limitations. By recognizing the potential confounders of the auscultatory assessment of blood pressure, the clinician minimizes the likelihood of enacting therapeutic decisions based on inaccurate data. When approaching the treatment of a hypertensive patient, several points should be kept in mind. First, the measurement of persistent and severe hypertension in a patient receiving treatment who describes symptoms of orthostatic hypotension with apparently adequate standing blood pressure or who lacks corroborating retinal, echocardiographic, or electrocardiographic signs of hypertension should raise the concern of pseudohypertension or a white-coat response. Similarly, when one finds a normal or near-normal systolic blood pressure in a patient with a clinical picture consistent with severe hypertension, one should make a directed effort to look for an unrecognized auscultatory gap. Second, marked discrepancies in measurements as obtained by different operators or in different settings should raise concern of the white-coat response or methodologic errors by one operator, such as undercuffing, excessive pressure on the head of the stethoscope, rapid deflation of the cuff, or use of different arms. In treating hypertension in even the minimally obese patient, a special point must be made that an adequate size cuff be used for all blood pressure determinations. Third, when blood pressure is determined with the patient in any but the satndardized back-and-arm-supported seated position described above, the clinician should acknowledge the possibility that the position may alter the patient's classification. Fourth, the diagnosis and management of hypertension requires multiple measurements of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7790986 TI - The search for low-cost, high-quality care: what are the assumptions and what are the questions now? PMID- 7790987 TI - Medical malpractice: the current reform proposals. PMID- 7790988 TI - Society of General Internal Medicine 18th annual meeting. San Diego, California, May 4-6, 1995. Abstracts. PMID- 7790984 TI - Housestaff team research in the ambulatory setting: it can be done. Internal Medicine Clinic Research Consortium Faculty. AB - Training in research has been recognized as an important component of internal medicine training. To provide a research experience for their residents, the authors established a team research project designed and implemented by postgraduate year-2 and -3 internal medicine trainees with guidance from general medicine faculty. A successful research project was conducted by trainees, which resulted in an award-winning poster presentation at a scientific meeting and publication in a peer-reviewed journal. The process of conducting a resident faculty team research project in the ambulatory care setting is described in this report. The authors encourage other internal medicine programs to consider resident team research efforts to expose a large number of trainees to a research experience. PMID- 7790989 TI - The trials and tribulations of interphase AgNORs. PMID- 7790990 TI - Morphometry in histopathology. PMID- 7790991 TI - Low incidence of mbr bcl-2/JH fusion genes in Hodgkin's disease. AB - Lymph node biopsies from 140 cases of Hodgkin's disease (HD) and from 30 non malignant lesions were screened for the presence of t(14;18) translocations involving the major breakpoint region (mbr) of the bcl-2 gene and the joining region (JH) of the immunoglobulin heavy chain gene, using a polymerase chain reaction (PCR) assay with subsequent nucleotide sequencing of amplified bcl-2/JH junctional regions. Expression of the bcl-2 protein within the Hodgkin and Reed Sternberg (HRS) cells was investigated in 86 cases of HD by immunohistochemistry on cryostat or paraffin sections. Although bcl-2 expression could be found in a proportion of neoplastic cells in up to one-third of HD cases, the frequency of t(14;18) gene fusions detected by PCR was low. We identified such gene fusions in only 3 out of 140 (2 per cent) HD cases, one biopsy of which presented with four clonally distinct bcl-2/JH sequences. No t(14;18) was found in any of 30 reactive lymph node lesions. All fusion gene sequences were unique regarding the localization of the chromosome 14 and 18 breakpoints and the extranucleotide N insertions. None of these gene fusions conformed to t(14;18) breakpoint sequences previously characterized in our laboratories. Our findings point to a mere coincidence in some cases of HD lesions and cells carrying a t(14;18) in the same biopsy and argue against a significant role of bcl-2 in the pathogenesis of HD. PMID- 7790992 TI - Interphase cytogenetic analysis of distinct X-chromosomal translocation breakpoints in synovial sarcoma. AB - Synovial sarcomas show a specific translocation involving chromosomes X and 18, t(X;18)(p11.2;q11.2). Two distinct X-chromosomal breakpoints occur in different synovial sarcoma tumour samples. These breakpoints are located within two related genomic regions containing ornithine aminotransferase-like sequences, termed OATL1 and OATL2. Preliminary observations indicated the potential correlation of OATL1-associated breakpoints with biphasic tumours and OATL2-associated breakpoints with monophasic fibrous tumours. The present study uses interphase cytogenetics to investigate the nature of chromosomal aberrations in frozen synovial sarcoma tissue samples. Two-colour fluorescence in situ hybridization (FISH) was performed using probes specific for the centromeres of chromosome X or 18, along with yeast artificial chromosome probes corresponding to the distinct breakpoint regions on Xp. One monophasic epithelial and two monophasic fibrous synovial sarcomas showed an OATL2-associated breakpoint, while a biphasic tumour revealed a hybridization pattern indicating a breakpoint within the OATL1 region. These results confirm our previous suggestion of a relationship between alternative breakpoints in Xp11.2 and different histological phenotypes observed in synovial sarcomas. They also demonstrate the utility of the two-colour hybridization approach for the identification of chromosomal changes in interphase nuclei isolated from frozen tissues. PMID- 7790993 TI - Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis. AB - The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours. PMID- 7790996 TI - Immunohistochemical localization of thrombomodulin in normal human skin and skin tumours. AB - Thrombomodulin (TM) expression has been investigated in sections of normal human skin, in cultured normal human keratinocytes, and in a variety of skin tumours. TM was present in squamous epithelial cells in the spinous layer of normal epidermis and in the outer root sheath of hair follicles, but was absent in the cells of the basal layer. It appeared to be predominantly localized to the cell membrane and the intercellular bridges in these areas. Cultured normal human keratinocytes demonstrated functionally active constitutive TM expression on their cell surface. Immunoperoxidase staining of skin tumours using anti-human TM antibodies demonstrated a typical cell membrane positivity in tumours with squamous or hair follicle differentiation. Basal cell carcinomas showed TM expression only in areas where incomplete squamoid metaplasia occurred. Sweat gland tumours and lesions of the melanogenic system failed to express TM. The localization of TM by immunostaining in various benign and malignant skin tumours typically correlated with their normal skin element of origin. The physiological significance of TM expression in the epidermis is currently undefined. PMID- 7790994 TI - Absence of overexpression of p53 protein by intestinal carcinoid tumours. AB - A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and overexpression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti-p53 protein antibody D07, overexpression was absent from a series of 22 intestinal carcinoid tumours (ten ileal, nine appendiceal, and three colorectal), nine overtly malignant, but was readily demonstrable in five of five colorectal adenocarcinomas, five of six cloacogenic carcinomas, and four of five squamous carcinomas of the anal canal used as controls. These observations are in keeping with previous similar studies of pulmonary carcinoid tumours and suggest possible differences in the pathogenesis of such neoplasms in comparison with non-endocrine differentiated tumours arising at equivalent sites. PMID- 7790995 TI - Experimental ulceration leads to sequential expression of spasmolytic polypeptide, intestinal trefoil factor, epidermal growth factor and transforming growth factor alpha mRNAs in rat stomach. AB - A model of gastric ulceration in the rat has been used to determine the expression of four messenger RNAs (mRNAs) encoding peptides considered to play active parts in the healing response. The trefoil peptides, rat spasmolytic polypeptide (rSP) and rat intestinal trefoil factor (rITF), along with epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) were the molecules studied. Ulceration was caused under anaesthesia by brief application of a liquid nitrogen-filled cryoprobe to the gastric serosal surface and RNA expression was monitored over the next 10 days. Each mRNA was quantified by ribonuclease protection assay, and mRNAs encoding rSP and rITF were localized within tissue sections by hybridization in situ with 35S antisense riboprobes. Ulceration induced the very rapid expression of first rSP and then rITF mRNA, whereas the mRNAs encoding EGF and TGF alpha increased at later times, with maxima recorded at 3 and 6 days, respectively. Hybridization in situ detected extensive rSP mRNA expression in the regenerative epithelia. The pronounced, but temporally different patterns of mRNA induction after ulceration suggest that the trefoil peptides may fulfil different and more immediate roles than the more 'traditional' healing proteins EGF and TGF alpha. PMID- 7790997 TI - Standardized staining and analysis of argyrophilic nucleolar organizer region associated proteins (AgNORs) in radically resected colorectal adenocarcinoma- correlation with tumour stage and long-term survival. AB - Quantification of silver-stained nucleolar organizer region associated proteins (AgNORs) was introduced in histopathology as a marker of cellular and nucleolar activity. However, due to the poor staining quality obtained on routinely processed archival material, the method yielded controversial and sometimes non reproducible results. The recent introduction of wet autoclave pretreatment has reliably improved AgNOR staining quality on routinely formalin-fixed and paraffin embedded tissues. In the present study, 92 routinely processed colorectal carcinomas were investigated, applying this novel staining technique. Subsequent standardized morphometric analysis revealed, irrespective of common tumour staging or grading classifications, a statistically highly significant correlation between AgNOR parameters and clinical course. The usefulness of standardized AgNOR parameters for the independent prediction of patient survival was proven by uni- and multivariate analysis. PMID- 7790998 TI - The autopsy. PMID- 7790999 TI - The method of calculating fractal dimension. PMID- 7791000 TI - In vivo action spectra, absorption and fluorescence excitation spectra of photosensitizers for photodynamic therapy. PMID- 7791001 TI - Photosensitization with derivatives of chlorin p6. AB - Biophysical and photobiological properties of three derivatives of chlorin p6 were examined. These agents can be considered as lysyl analogs of the aspartyl chlorin NPe6. Lysyl chlorin p6 diester (LCP) and the triester analog (LCP2) were readily accumulated by murine leukemia L1210 cells, localized in lysosomes, and were relatively inefficient photosensitizing agents in vitro. In contrast, lysyl chlorin e6 imide (LCI) was poorly accumulated, concentrated in mitochondrial and plasma membranes, but was more efficacious. LCI was the most effective agent with regard to photosensitization of a murine tumor in vivo, but all three agents caused substantially more toxicity than was observed with NPe6. PMID- 7791002 TI - Fluorescence spectroscopy of pH in vivo using a dual-emission fluorophore (C SNAFL-1). AB - The aim of this study was to evaluate a dual-emission fluorophore (C-SNAFL-1: 5'(and 6')-carboxyseminaphthofluorescein) for in vivo pH monitoring, using one excitation wavelength and two emissions. P388-tumour-bearing CDF mice were injected intravenously with C-SNAFL-1. Glucose was administered simultaneously to lower the tumour pH. Under our experimental conditions, tissue autofluorescence was found to be negligible. Two emission peaks were observed. The wavelength of the first one was pH insensitive (545 nm). The second one was pH sensitive: a shift of the emission peak as a function of pH was observed from 587 nm for pH 7.25 to 605 nm for pH 6.3. A calibration curve linking emission intensity ratios (I545/I635) to in vivo pH is provided. Results clearly indicate differences between tumorous (ratio 0.55 +/- 0.08, pH 6.3 +/- 0.1) and normal (ratio 1.39 +/- 0.04, pH 7.25 +/- 0.1) tissues. The concept of pH fluorescence spectroscopy in vivo using C-SNAFL-1 provides quantified data and accurate measurements of tissue pH. PMID- 7791003 TI - Correlation between meta(tetrahydroxyphenyl)chlorin (m-THPC) biodistribution and photodynamic effects in mice. AB - Analysis of sensitizer kinetics is essential for the performance of light irradiation when tumour concentration and tumour-to-normal tissue ratios are optimal. In this study nude mice were grafted with human adenocarcinoma 15 days before meta(tetrahydroxyphenyl)chlorin (m-THPC) intra-peritoneal (IP) injection. Fluorescence was recorded through an optic fibre spectrofluorometer at 650 (the most intense) and 714 nm, with intensity being proportional to injected dose. In tumour, skin and muscle the maximum fluorescence was obtained with 1.6 mg kg-1 72 h after injection (44 counts per second). Tumour-to-skin and tumour-to-muscle ratios obtained by high performance liquid chromatography (HPLC) analysis and spectrofluorometric measurements decreased between 12 and 72 h (from 15 to 1.5), indicating that tumour selectivity decreases with time. This contrast between selectivity and fluorescence levels was also observed with photodynamic therapy (PDT) results, for which no differences were observed when 10 J cm-2 were delivered at 100 or 200 mW. PDT results were better 24 h after drug administration than at 72 h. Tumour growth decrease (-40%) was found when 1.6 mg kg-1 were injected 24 h before irradiation. For other groups a slower increase (12% vs. 23%) was noted in the first few days after PDT. The paradoxal correlation between fluorometric or HPLC measurements and PDT effects suggests that m-THPC localizes differently with time in tumour components. PMID- 7791004 TI - Malignancies and atherosclerotic plaque diagnosis--is laser induced fluorescence spectroscopy the ultimate solution? AB - A non-invasive diagnostic tool that can identify diseased tissue sites in situ and in real time could have a major impact on the detection and treatment of cancer and atherosclerosis. A review of the research performed on the utilization of laser induced fluorescence spectroscopy (LIFS) as a means of diseased tissue diagnosis is presented. Special emphasis is given to problems which were raised during clinical trials and recent experimental studies. The common origin and possible solution of these problems are shown to be related to, firstly, the identification of the fluorescent chemical species, secondly, the determination of the excitation/collection geometry and its effect to the method and, finally, the further elaboration on the laser-tissue interaction. PMID- 7791006 TI - Fluorescence and absorption spectroscopic properties of RNA 5'-cap analogues derived from 7-methyl-, N2,7-dimethyl- and N2,N2,7-trimethyl-guanosines. AB - Absorption and fluorescence properties of several cap analogues, namely nucleosides, nucleoside 5'-monophosphates and P1,P3-dinucleoside triphosphates derived from 7-methylguanine, N2,7-dimethylguanine and N2,N2,7-trimethylguanine, have been studied. The data obtained include the absorption and fluorescence spectra of the cationic (N1-protonated) and zwitterionic (N1-deprotonated) species, the pKa values of the ground and excited states of the methylated base moiety and the effect of temperature and solvent composition (mixtures of water and 1,4-dioxane) on the fluorescence intensity. Furthermore, the fluorescence lifetimes of N2,N2,7-trimethylguanosine 5'-triphosphate and P1-guanosine(5')-P3 [N2,N2,7-trimethylguanosine(5')] triphosphate have been determined as a function of temperature. These data clearly indicate that dynamic quenching must be taken into account when the extent of the intramolecular stacking of the latter compound is estimated by fluorescence spectroscopy. PMID- 7791005 TI - Molecular dosimetry by flow cytometric detection of thymine dimers in mononuclear cells from extracorporally UV-irradiated blood. AB - UV-induced DNA damage in mononuclear leucocytes can be quantified by flow cytometry of fluorescence from a labelled monoclonal antibody that specifically binds to thymine dimers (T<-->T): specific fluorescence is already detectable after exposures of 1-2 J m-2 of 254 nm radiation and shows a linear relationship with dose. The distribution of UV fluences over an irradiated volume can thus be ascertained by measuring the UV-induced T<-->T loads of the individual cells from that volume. After irradiation of mononuclear cells in a phosphate buffer solution in a Petri dish, most cells showed a similar intensity of specific T<- >T fluorescence, forming a single sharp peak in the fluorescence histogram. This signifies an even distribution of fluences over the cells. It was noticed, however, that a variable minor fraction of mononuclear cells (usually less than 10%) could be resistant to immunostaining; this fraction was rejected from the calculation of the specific fluorescence. The flow cytometric technique was also applied to blood cells exposed in an ISOLDA device, which is in use in Russian clinics for UV irradiation of whole blood for therapeutical purposes. Only a small fraction of mononuclear cells in a sample of whole blood treated in ISOLDA acquired a detectable T<-->T load after exposure to lamps which emit predominantly either UVC or UVB light ((3.6 +/- 1.0)% and (1.8 +/- 0.4)% of all analysed cells respectively). This small fraction had received a large variation in fluences, resulting in differences in nuclear T<-->T loads by a factor of 200.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791008 TI - Effects of vacuum UV and UVC radiation on dry E. coli plasmid pUC19. I. Inactivation, lacZ- mutation induction and strand breaks. AB - Using Escherichia coli plasmid pUC19 as a test system to study the effects of radiation on DNA at the molecular level, the wavelength (160-254 nm) dependence of inactivation (loss of the ability to transform E. coli), mutation induction in the target gene lacZ and induction of single-strand breaks and double-strand breaks was investigated. The same fluences were applied for all endpoints tested. In the UVC range, the cross-sections of inactivation and mutation induction match the DNA absorption curve, whereas the cross-section for single-strand break induction deviates from the DNA curve, especially at 220 nm. In the vacuum UV range, with increasing energy of the photons, the cross-sections of inactivation and single-strand breaks increase sharply (from 190 to 160 nm by more than one order of magnitude), which is not reflected by the DNA curve. In this UV range, the shape of the action spectrum is similar to that of the absorption curve of the sugar phosphate moiety of DNA. Only after irradiation with vacuum UV at 160 nm are double-strand breaks detected. Their induction rate is about one order of magnitude lower than that of single-strand breaks at the same wavelength; however, their induction rate is at least twice that of single-strand breaks at longer wavelengths. Concerning mutation induction, the increment in the vacuum UV range is less well expressed. The data suggest the contribution of different kinds of photochemical injury to inactivation and mutation induction. PMID- 7791009 TI - Evidence of photoenzymatic repair due to the phrA gene in a phrB mutant of Escherichia coli K-12. AB - The role of the phrA gene in the genetic control of photoreactivation in Escherichia coli has been a matter of some controversy. It has been proposed that the gene has no significant physiological role in photoreactivation. However, we have previously sequenced a restriction fragment thought to contain the phrA gene and shown it to contain a putative gene. When this gene, termed the putative phrA gene, was transformed into a phrAphrB mutant, a photoreactivable response above that of the phrAphrB mutant was observed. It has been suggested that the photorepair seen in phrB mutants is due to Type III photoreactivation, which is independent of temperature and fluence rate effects. Here we have shown that the photorecovery associated with the phrA gene is dependent on both temperature and fluence rate. This suggests that the photorecovery is not due to Type III photoreactivation but to an enzymatic reaction caused by an unknown photoactive protein, the phrA gene product, which acts on lesions other than pyrimidine dimers, possibly pyrimidine (6-4) pyrimidone photoproducts. We therefore propose that the phrA gene be reaccepted and its role in photoreactivation in Escherichia coli acknowledged. PMID- 7791007 TI - Characterization of the reactive intermediates in laser flash photolysis of adenine, adenosine and dAMP using acetone as photosensitizer. AB - Transient absorption spectra of adenine, adenosine and 2'-deoxyadenosine 5' monophosphate (dAMP) arising from 248 nm laser flash photolysis using acetone as a photosensitizer have been observed. The intermediates recorded are assigned to the excited triplet states and dehydrogenated radicals of adenine and its nucleoside and nucleotide. The excited triplet states of adenine and its derivatives are produced via triplet-triplet excitation transfer and observed for the first time, while the dehydrogenated radicals stemming from the interaction of triplet acetone with adenine and its derivatives via electron transfer through a five-member-ring electron donor-acceptor intermediate. The site of dehydrogenation is suggested to be the hydrogen atom on C(8) of the adenine moiety. Moreover, three sets of kinetic parameters of the triplet decay have been determined. The rate constants of the unimolecular decay (k0), the triplet quenching by the ground state (ksq) and by the triplet quencher Mn2+ (kq) are 1.1 x 10(5), 7.9 x 10(4), 3.7 x 10(4) s-1, 6.9 x 10(8), 8.3 x 10(8), 3.6 x 10(8) dm3 mol-1 s-1 and 4.2 x 10(8), 3.5 x 10(8), 6.0 x 10(8) dm3 mol-1 s-1 respectively for adenine, adenosine and dAMP. PMID- 7791010 TI - Flow cytometric determination of absolute membrane potential of cells. AB - Membrane potential measurements using fluorescent membrane potential indicator dyes report on relative changes but usually do not result in an absolute value of the measured parameter. The method developed in this paper is based on the assumption that the negatively charged bis-oxonol distributes across the cytoplasmic membrane according to the Nernst equation. It is further supposed that the fluorescence intensity measured from a given stained cell is a single value function of the intracellular dye concentration. The protocol suggested incorporates the construction of a calibration curve (fluorescence intensity measured from stained cells vs. extracellular dye concentration). This allows the evaluation of the membrane potential in millivolts using fluorescence readings of the cells both in the depolarized state and in the state of interest. Good agreement was found between absolute membrane potential data of human peripheral blood lymphocytes by our method and results of parallel patch clamp measurements. PMID- 7791011 TI - Are antiepileptic drugs harmful when taken during pregnancy? AB - According to recent experiences. There are no specific teratogenic effects of antiepileptic drugs in humans. Polytherapy is associated with malformations more often than monotherapy. This does not apply to minor anomalies. Concerns regarding neural tube defects because of intrauterine valproate--or carbamazepine -exposure can be met by. Taking a careful history regarding individual or family predisposition to defects or anomalies. Dividing the daily dose into several single doses. Folate supplementation prior and during pregnancy. Antenatal monitoring. Those minor anomalies (hypertelorism, distal digital hypoplasies), which may possible be induced by antiepileptic drugs harmonize or disappear during further development. Most minor anomalies, small body measurements, small head circumferences and cognitive dysfunction are not caused by ingestion of antiepileptic drugs during pregnancy. PMID- 7791012 TI - Genetic and non genetic factors in the outcome of diabetic pregnancy. AB - In insulin-dependent diabetes mellitus, maternal Phosphoglucomutase genotype is a predictor of fetal macrosomia much more important than quality of metabolic control during pregnancy. In gestational diabetes and in non insulin-dependent diabetes, on the contrary, the most important predictor is the metabolic control of diabetes. PMID- 7791013 TI - The performance of a new valveless ventilator at rates of up to 250 bpm. AB - The efficacy of a new ventilator, incorporating a valveless pneumatic exhalation circuit, at rates of up to 250 bpm was first assessed in the laboratory. Using this ventilator the effect of fast rate ventilation on blood gases of infants with acute respiratory distress was then examined. Infants were studied at three rates: 60, 125 and 250 bpm. Peak inflating and positive end expiratory pressure, inspiratory: expiratory ratio and inspired oxygen were kept constant. The laboratory study demonstrated that as ventilator rate was increased the delivered volume fell, but even at 250 bpm the delivered volume was 7 ml. In the clinical study, oxygenation at 250 bpm was not significantly different from that at 60 bpm, but significantly lower than at 125 pbm. Carbon dioxide levels were significantly lower at 250 bpm that at 60 bpm, but did not differ significantly from that at 125 bpm. We conclude increasing ventilator rate from 125 to 250 bpm is not advantageous for infants ventilated for acute respiratory distress. PMID- 7791015 TI - Efficacy and safety of a 2-tier prostaglandin labor induction schedule. AB - OBJECTIVES: To determine the efficacy and safety of a 2-tier, Bishop score-driven induction schedule using gel and tablet formulations of PGE2 to establish new monitoring guidelines. DESIGN: Prospective descriptive study. SETTING: eight Germany University obstetric departments. SUBJECTS: 467 high risk patients. INTERVENTIONS: Bishop score < 5: intracervical 0.5 mg PGE2 gel; Bishop score 5-7: intravaginal 3 mg PGE2 tablet. MAIN OUTCOME MEASURES: Uterine hyperstimulation: > 5 contractions/min, contraction duration > 2 min and emergency tocolytic therapy; perinatal outcome: secondary caesarean section rate, operative vaginal delivery and fetal acidosis. RESULTS: PGE2 induction resulted in spontaneous delivery in 76.9% (6.4% fetal acidosis) and 14.1% secondary c. section. The gel was associated with more adverse uterine effects and a poorer fetal outcome than the tablet. Adverse uterine events increased significantly on repeat dosing with the gel (39.5 vs 29.3%), but not the tablet: they also increased with a dosing interval < 8 h with either formulation. Overall, adverse uterine events were fewer and perinatal outcome better in multiparae than in nulliparae. CONCLUSIONS: The higher adverse uterine event rate with the gel should be viewed against the backdrop of the low Bishop score. The interval between repeat dosing should not be less than 8 h after PGE2 gel treatment. Primigravidae must be monitored with special care following labour induction with PGE2. PMID- 7791016 TI - Prenatal expectations and fears in pregnant women. AB - The aim of this study was to extend the medical knowledge of the prenatal expectations and wishes of pregnant women with respect to themselves, their partners and the maternity ward selected for the approaching birth, and also of the anxieties arising in this connection. In summary, our study shows that the desire to experience birth in the most natural, undisturbed and unmanipulated form possible is reiterated frequently, but is relativized by the intense need to be reassured of the safety of the unborn child. Fears experienced before the birth were focused accordingly on the condition of the child, although 25% of the women questioned acknowledged a marked fear of helplessness and failure. The obstetric team were expected to offer, as far as possible, the continuous personal supervision of a doctor and a midwife who were prepared to allow the patient the responsibility of being involved in obstetric decisions. PMID- 7791014 TI - Guillain-Barre syndrome in pregnancy--an indication for caesarian section? AB - Guillain-Barre syndrome (GBS) in pregnancy is a rare neurological disorder which confronts the obstetrician with a difficult decision regarding the management of pregnancy and delivery. Two case reports illustrate the problems of obstetrical and neurological patient management. We thereby discuss indications for intervention based on the reciprocal influences of GBS and pregnancy. In acute GBS intervention by induction of labor or caesarian section seems to provoke deterioration of the patient's condition and delayal of recovery. PMID- 7791017 TI - Repeated direct fetal intravascular high-dose immunoglobulin therapy for the treatment of Rh hemolytic disease. AB - Recently, administration of high-dose intravenous immunoglobulin (HDivIG) either to the mother or the neonate has been proposed in an effort to prevent progressive hemolysis in Rh(D) perinatal disease, but no cases have been published with direct fetal HDivIG administration. We report a case in which HDivIG was repeatedly administered by cordocentesis to a fetus affected by Rh(D) disease from 28 to 36 weeks gestation, at doses of approximately 450 mg/kg. The fetus required no transfusions, and the neonatal evolution was satisfactory. The treatment, performed at three weeks intervals, seemed to be useful in preventing fetal hemolysis. No fetal complications were present. Recurrent administration of HDivIG therapy to the fetus in cases of severe Rh(D) disease, appears to be feasible and free of serious complications to the fetus or the mother. PMID- 7791018 TI - Changes in apnea and autoresuscitation in piglets after intravenous and intrathecal interleukin-1 beta injection. AB - Piglets were given IL-1 beta intravenously (Index I, n = 8) or intrathecally (Index II, n = 9) prior to apnea to test the hypothesis that IL-1 beta may prolong periods of apnea during sleep and infection. Apnea variables and the quality of autoresuscitation were recorded and compared to an apnea control group (Ctr. I, n = 7, apnea without injection of IL-1 beta) and a procedure control group (Ctr. II, n = 6, apnea after intratecally injected sterile water). Hypoxanthine (Hx) and xanthine (X) were analyzed in plasma, CSF and vitreous humor. The duration of apnea was significantly longer in the Index I - mean: 38, intraquartile range: 27-52 sec and Index II-group 26 (24-36) sec than in the Ctr. 1-12 (10-13) sec (p < 0.01) and the Ctr. II-group 14 (6-18) sec (p < 0.01). The number of respirations per 2 min following apnea in the Index I-group mean: 21, intraquartile range: 7-40 and was significantly less than in the Ctr. I-group 109 (39-150) (p < 0.01), while a similar tendency was found in the Index II-group 42 (27-55) (p = 0.06). IN CONCLUSION: Intravenous and intrathecal injection of IL-1 beta prolong the duration of apnea and modifies autoresuscitation. PMID- 7791019 TI - Vascularization of yolk sac and vitelline duct in normal pregnancies studied by transvaginal color and pulsed Doppler. AB - The yolk sac is an organ of increasingly recognized importance in the initial mechanisms of pregnancy maintenance and the early growth and welfare of the embryo. Having a complex protein secretion and an equally intricate ultrastructure, it is the primary source of blood and germ cells. This small and to date largely ignored structure may have a vital and interesting part to play in human embryonic development, which may be comparable to its proven evolutionary importance in other animals. The aim of our study was to assess the vascularity of the yolk sac and vitelline duct in 105 patients between the 6th and 10th weeks of gestation who were scheduled for termination of pregnancy for psychosocial reasons. The patients were divided in five subgroups depending on the duration of gestation. All of them had a normal developing pregnancy with no clinical symptoms of pathology (e.g. bleeding in early pregnancy). Gestational age was calculated from the first day of the last menstrual period and substantiated by crown-rump (CRL) measurements. After exploration of the gestational sac and embryo by transvaginal sonography, color Doppler was used to image the yolk sac and vitelline duct vascularity. The visualized vessels were analyzed with pulsed Doppler using the sample volume unit set of 1 mm. The assessment of obtained waveform signals was made by means of peak systolic Doppler shift (PSV) and pulsatility index (PI). The pulsatility index was calculated as a difference between peak systolic and end diastolic Doppler shift divided by the mean maximum velocity. At least 5 separate cardiac cycles were measured, and the mean value was calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791021 TI - Prenatal thoracocentesis may be lifesaving in congenital chylothorax. PMID- 7791022 TI - Surface characterization: understanding sources of variability in the production and use of pharmaceuticals. PMID- 7791020 TI - Fetal and uteroplacental flow velocity waveforms in abruptio placentae: report of two cases. AB - This paper reports two cases of abruptio placentae assessed using pulsed Doppler at 29 and 30 weeks of gestation. Transvaginal pulsed Doppler showed abnormal uterine artery FVWs in both cases. One fetus with normal umbilical and normal middle cerebral artery FVWs was not acidotic and only midly hypoxic, whereas the other fetus with normal umbilical and abnormal middle cerebral artery FVWs was severely acidotic and hypoxic at birth. It is suggested that Doppler assessment of fetal blood distribution is of great value for the rapid diagnosis of fetal asphyxia, and that uteroplacental FVWs provide reliable information on which to base the diagnosis of abruptio placentae. PMID- 7791023 TI - An attempt to clarify the mechanism of the penetration enhancing effects of lipophilic vehicles with differential scanning calorimetry (DSC). AB - In a previous in-vivo skin penetration study, it was observed that certain lipophilic liquid vehicles enhanced drug penetration, whilst others did not. To clarify the mechanism of skin penetration enhancement, isolated sheets of human stratum corneum were measured by differential scanning calorimetry (DSC), either untreated or after pretreatment with various lipophilic liquids (highly purified light mineral oil, isopropyl myristate, caprylic/capric acid triglycerides containing 5% phospholipids, dibutyl adipate, dimethicone 100, cetearyl iso octanoate, caprylic/capric acid triglycerides), commonly used in ointment bases. All samples were analysed over a heating range of at least--10-130 degrees C. All DSC curves were evaluated with regard to the phase-transition enthalpies (peak areas) and peak maximum temperatures of the lipid-phase transitions at ca 75 and 85 degrees C. With the exception of dimethicone 100, cetearyl iso-octanoate and caprylic/capric acid triglycerides, all vehicles showed characteristic alterations of the phase-transition temperatures and enthalpies of the stratum corneum lipids. Mineral oil and isopropyl myristate caused a reduction of the enthalpy and a decrease of the phase-transition temperatures. These two vehicles are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly partially dissolve the lipids. Dibutyl adipate and caprylic/capric acid triglycerides containing 5% phospholipids decreased the phase-transition enthalpy only, probably due to dissolution or extraction of the stratum corneum lipids. These DSC results provide an explanation for the in-vivo penetration-enhancing effects observed previously. PMID- 7791024 TI - Pharmacokinetic properties and interactions with blood components of N4-hexadecyl 1-beta-D-arabinofuranosylcytosine (NHAC) incorporated into liposomes. AB - N4-Hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC) is a new lipophilic derivative of 1-beta-D-arabinofuranosylcytosine (ara-C) with strong antitumour activity. The interactions of NHAC incorporated into small unilamellar liposomes of different compositions with blood components were evaluated. In comparison with ara-C, NHAC is highly protected against deamination to inactive arabinofuranosyluracil (ara-U) in human plasma, resulting in only 2% conversion into ara-U after 4 h incubation at 37 degrees C, whereas from ara-C more than 80% was deaminated. In in-vitro incubations with human blood, it was found that NHAC was transferred from the liposomes at about 47% efficiency to plasma proteins, particularly to albumin and to the high and low density lipoproteins. The remaining part of NHAC was bound to erythrocytes (50%) and to leucocytes (3%). The addition of poly(ethylene) glycol-modified phospholipids to the liposomes (PEG liposomes), which were composed of soy phosphatidylcholine and cholesterol (plain liposomes), did not significantly prevent the fast transfer of NHAC from the liposomes to the blood components. Pharmacokinetic studies in mice revealed that NHAC had biphasic kinetics in blood with a t1/2 alpha of 16 min and a t1/2 beta of 3.8 h when the drug was formulated in plain liposomes and a t1/2 alpha of 15 min and a t1/2 beta of 9.67 h in PEG liposomes, respectively. NHAC was predominantly distributed in the liver with 29% of the injected dose found after 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791025 TI - Effect of policosanol on lipofundin-induced atherosclerotic lesions in rats. AB - Policosanol is a mixture of higher aliphatic alcohols isolated from sugar cane wax, showing cholesterol-lowering effects and preventing the development of lipofundin-induced lesions in New Zealand rabbits. This study was conducted to determine whether policosanol orally administered to rats also protects against the development of lipofundin-induced atherosclerotic lesions. Fifty four male Wistar rats were randomly distributed amongst a negative control group, a positive control group intravenously injected with lipofundin for eight days, and four experimental groups also injected with lipofundin, but orally receiving policosanol at 0.5, 2.5, 5 and 25 mg kg-1, respectively. Policosanol treatment was orally administered once-a-day for eight days, while control groups similarly received equivalent amounts of vehicle. A significant reduction of the atherosclerotic lesions in the treated animals was observed. It is concluded that policosanol has a protective effect on lipofundin-induced aortic lesions in Wistar rats. PMID- 7791026 TI - Comparative convulsant potencies of two carbapenem derivatives in C57 and DBA/2 mice. AB - The behavioural and convulsant effects of imipenem and meropenem were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizure, and in C57 mice, a strain not prone to seizure. DBA/2 mice were more susceptible than C57 mice to seizures induced by imipenem-cilastatin or meropenem. Imipenem was also 1.9 times more potent than meropenem in inducing clonus in DBA/2 mice. To investigate the possibility that the seizure-inducing activity of imipenem might be due to a probenecid-like effect of cilastatin, animals were treated with imipenem alone. No significant differences were observed between imipenem-cilastatin and imipenem-treated animals. Thus, it is reasonable to exclude a probenecid-like effect of cilastatin. Although the main mechanism for seizure-like activity of imipenem cannot be easily determined, we believe that several mechanisms may be involved. An increased excitation of the central nervous system (CNS) by inhibition of GABA binding to receptors and a slow clearance of imipenem from the CNS may be postulated. Cilastatin did not induce seizures. In addition, meropenem, a compound structurally related to imipenem, showed weak or no convulsant effects. PMID- 7791027 TI - Properties of a resiniferatoxin-stimulated, calcium inhibited but phosphatidylserine-dependent kinase, which is distinct from protein kinase C isotypes alpha, beta 1, gamma, delta, epsilon and eta. AB - We have separated a resiniferatoxin-stimulated histone-kinase activity from human neutrophils, elicited mouse macrophages and murine alveolar macrophages by hydroxyapatite chromatography. The assay conditions for resiniferatoxin kinase were optimized as part of this study and in the presence of phosphatidylserine but absence of Ca2+ the Ka for histone IIIs phosphorylation by resiniferatoxin was calculated as 16 nM. Using a phosphate gradient of 20-500 mM, peaks of protein kinase C activity could be washed from the hydroxyapatite column in 300 nM phosphate and resiniferatoxin kinase recovered in 500 mM phosphate. At the optimum concentration of 160 nM, the ability of resiniferatoxin to induce enzyme activity was compared with a range of phorbol esters all at the same concentration. These related compounds failed to activate resiniferatoxin kinase although they have previously been shown to activate protein kinase C isotypes. Similarly sn-1,2,-dioleoylglycerol and the potent irritant capsaicin at 30 microM failed to activate the kinase. A Scatchard analysis of [3H] phorbol dibutyrate binding produced a linear plot (Kd 41.6 nM; Bmax 11.6 fmol unit-1) and binding was inhibited by resiniferatoxin and 12-O-tetradecanoylphorbol-13-acetate (TPA), with resiniferatoxin 700 times more potent than TPA in this respect. A radiolabelled resiniferatoxin binding assay was also used to demonstrate specific binding of [3H]resiniferatoxin which could be inhibited by unlabelled compound. Resiniferatoxin kinase activity was shown to be distinct from the protein kinase C isotypes alpha, beta 1, gamma, delta and epsilon by means of immunological analysis and from the eta isotype, because that isotype was not stimulated by resiniferatoxin but was stimulated by TPA when a pseudosubstrate was used. In addition the resiniferatoxin-stimulated activity was inhibited in-vitro by the addition of Ca2+ (Ki 0.1-0.5 nM free Ca2+). Further purification of resiniferatoxin kinase by Superose chromatography indicated a major activity fraction of about 70-90 kDa. Thus resiniferatoxin kinase, isolated from human and mouse inflammatory cells is distinct from the known isotypes of protein kinase C and is a major resiniferatoxin receptor. PMID- 7791028 TI - The effects of racemic, (+)- and (-)-pinacidil on the membrane potential of the rat aorta. AB - The endothelium-intact and -denuded rat aorta is hyperpolarized by racemic and ( )-pinacidil, probably by opening ATP-dependent potassium channels. (+)-Pinacidil caused depolarization of the endothelium-intact and -denuded rat aorta. The depolarization induced by 20 mAM KCl in the endothelium-intact rat aorta was reversed by racemic and (-)-, but not by (+)-pinacidil. On the endothelium-intact rat aorta, isoprenaline produced hyperpolarization and ICI 118551 (erythro-(+/-) 1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol) had no effect alone but prevented isoprenaline from causing hyperpolarization. The hyperpolarization induced by isoprenaline was reversed by racemic and (+)-, but not by (-) pinacidil. Glibenclamide depolarized the endothelium-intact rat aorta and prevented the hyperpolarizing action of racemic pinacidil and (-)-pinacidil. (+) Pinacidil prevented the hyperpolarizing action of (-)-pinacidil. Glibenclamide is probably preventing the hyperpolarization associated with opening of the ATP dependent potassium channel by blocking this channel. Several mechanisms may underlie the depolarizing action of (+)-pinacidil, including blocking of ATP dependent potassium channels. PMID- 7791029 TI - In-vitro pharmacology of sarpogrelate and the enantiomers of its major metabolite: 5-HT2A receptor specificity, stereoselectivity and modulation of ritanserin-induced depression of 5-HT contractions in rat tail artery. AB - The new antiplatelet agent sarpogrelate (MCI-9042), its major metabolite (R,S)-1 [2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2- propanol ((R,S)-M-1) and the enantiomers of (R,S)-M-1 were studied as antagonists at 5-HT2A receptors, 5-HT1-like receptors, 5-HT3 receptors, alpha 1-adrenoceptors, beta-adrenoceptors, histamine H1 receptors, histamine H2 receptors and muscarinic M3 receptors in various functional in-vitro assays. Sarpogrelate, (R,S)-M-1, (R)-M-1 and (S)-M-1, respectively, were competitive antagonists of 5-hydroxytryptamine (5-HT) at 5 HT2A receptors of rat tail artery with calculated pA2 values of 8.53, 9.04, 9.00 and 8.81, respectively. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). Stereoselectivity of M-1 enantiomers was low. (R)-M-1 showed 1.6-fold, 2,3-fold and 2.5-fold higher antagonist activity than (S)-M-1 for 5-HT2A, H1 and M3 receptor, respectively. Affinity at beta-adrenoceptors and 5-HT1-like receptors was 5-fold and 3-fold higher for (S)-M-1 than for (R)-M-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791030 TI - The transhepatic response to noradrenaline in the rabbit liver: the influence of arterioportal pressure gradient. AB - The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10(-10)-10(-4) mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline. At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68.5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged. These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance. PMID- 7791031 TI - Irreversible inhibition of rat liver mitochondrial MAO A and MAO B by enantiomers of deprenyl and alpha-methylpargyline. AB - Using rat liver mitochondrial monoamine oxidase (MAO) A and MAO B, the possible influence of stereochemical factors upon the irreversible inhibition by propargylamine derivatives has been studied using the enantiomers of deprenyl and of alpha-methylpargyline. Whether studying the inhibition of MAO A or MAO B, little difference was found among enantiomeric pairs in the first-order rate constant (k2) for formation of the enzyme inhibitor adduct. Similarly, and with the exception of (S)-D-(+)-deprenyl (k2 = 0 or an extremely low value at MAO A), the computed value of k2 for the individual enantiomers showed little variation between MAO A and MAO B. These results suggest that inhibitor selectivity towards a particular form of the enzyme is determined predominantly at the competitive phase of the inhibition. PMID- 7791032 TI - Antiplatelet effect of gingerol isolated from Zingiber officinale. AB - The purpose of this investigation was to determine the antiplatelet mechanism of gingerol. Gingerol concentration-dependently (0.5-20 microM) inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha) and thrombin. Gingerol also concentration-dependently (0.5-10 microM) inhibited thromboxane B2 and prostaglandin D2 formation caused by arachidonic acid, and completely abolished phosphoinositide breakdown induced by arachidonic acid but had no effect on that of collagen, PAF or thrombin even at concentrations as high as 300 microM. In human platelet-rich plasma, gingerol and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate (ADP, 5 microM) and adrenaline (5 microM) but had no influence on the primary aggregation. The maximal antiplatelet effect was obtained when platelets were incubated with gingerol for 30 min and this inhibition was reversible. It is concluded that the antiplatelet action of gingerol is mainly due to the inhibition of thromboxane formation. PMID- 7791033 TI - The disposition of morphine and its metabolites in the in-situ rat isolated perfused liver. AB - A specific HPLC method with UV detection was used to investigate the disposition of morphine and its metabolites in the in-situ rat isolated perfused liver preparation. Livers of male Sprague-Dawley rats (n = 4) were perfused under single pass conditions with protein- and erythrocyte-free perfusate, containing 2.66 microM morphine, for up to 90 min. The concentration of morphine, normorphine and morphine-3-glucuronide (M3G) in outflow perfusate, and the biliary excretion of M3G and normorphine glucuronide, all reached steady-state levels within 15-20 min after commencing perfusion. At steady-state, the mean (+/ s.d.) extraction ratio of morphine was 0.87 +/- 0.06 and clearance (26.0 +/- 1.7 mL min-1) approached perfusate flow rate (30 mL min-1). Although M3G was the main metabolite, accounting for 72.8 +/- 12.7% of eliminated morphine, a significant proportion (21.6 +/- 13.5%) was N-demethylated to normorphine and was recovered as unchanged normorphine in outflow perfusate and normorphine glucuronide in bile. The biliary extraction ratio of hepatically-formed M3G was 0.61 +/- 0.31. Results from an additional six experiments, in which livers were perfused with 1.33 and 2.66 microM of morphine for 30 min each in a balanced cross-over manner, indicated that the disposition of morphine and its metabolites was approximately linear within this concentration range. PMID- 7791034 TI - High-performance liquid chromatographic determination of trazodone and 1-m chlorophenylpiperazine with ultraviolet and electrochemical detector. AB - A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C8 reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100-2000 ng mL-1 and for m-CPP in the concentration range 5-100 ng mL-1. The recoveries of trazodone and m-CPP added to plasma were 81.0-84.2 and 68.0-73.2%, respectively, with coefficients of variation of less than 7.3 and 8.2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone. PMID- 7791035 TI - Determination of octanol-water partition coefficients by an HPLC method for anticonvulsant structure-activity studies. AB - Octanol-water partition coefficients have been measured and calculated for eight clinically relevant anticonvulsants. For some compounds, these are the first experimentally available log P values. For the remainder of the molecules, new values have been suggested. The utility of the micro shake-flask experimental method and the ALOGP calculational method in determining anticonvulsant log P values has been demonstrated. PMID- 7791036 TI - Physiologically based pharmacokinetic study on a cyclosporin derivative, SDZ IMM 125. AB - The immunosuppressant, SDZ IMM 125 (IMM), is a derivative of cyclosporin A (CyA). The disposition kinetics of IMM in plasma, blood cells, and various tissues of the rat was characterized by a physiologically based pharmacokinetic (PBPK) model; the model was then applied to predict the disposition kinetics in dog and human. Accumulation of IMM in blood cell is high (equilibrium blood cell/plasma ratio = 8), although the kinetics of drug transference between plasma and blood cell is moderately slow, taking approximately 10 min to reach equilibrium, implying a membrane-limited distribution into blood cells. A local PBPK model, assuming blood-flow limited distribution and tissue/blood partition coefficient (KP) data, failed to adequately describe the observed kinetics of distribution, which were slower than predicted. A membrane transport limitation is therefore needed to model dynamic tissue distribution data. Moreover, a slowly interacting intracellular pool was also necessary to adequately describe the kinetics of distribution in some organs. Three elimination pathways (metabolism, biliary secretion, and glomerular filtration) of IMM were assessed at steady state in vivo and characterized independently by the corresponding clearance terms. A whole-body PBPK model was developed according to these findings, which described closely the IMM concentration-time profiles in arterial blood as well as 14 organs/tissues of the rat after intravenous administration. The model was then scaled up to larger mammals by modifying physiological parameters, tissue distribution and elimination clearances; in vivo enzymatic activity was considered in the scale-up of metabolic clearance. The simulations agreed well with the experimental measurements in dog and human, despite the large interspecies difference in the metabolic clearance, which does not follow the usual allometric relationship. In addition, the nonlinear increase in maximum blood concentration and AUC with increasing dose, observed in healthy volunteers after intravenous administration, was accommodated quantitatively by incorporating the known saturation of specific binding of IMM to blood cells. Overall, the PBPK model provides a promising tool to quantitatively link preclinical and clinical data. PMID- 7791037 TI - A non-Markovian model for calcium kinetics in the body. AB - We present a new generalized compartmental model for calcium kinetics as measured by tracer concentration in blood plasma. The parameter measuring incorporation of calcium in bone discriminates between different levels of physical development in female teenagers and between teenagers and adults. PMID- 7791038 TI - Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models. AB - The objectives of this investigation were to characterize the disposition of fentanyl and alfentanil in 14 tissues in the rat, and to create physiological pharmacokinetic models for these opioids that would be scalable to man. We first created a parametric submodel for the disposition of either drug in each tissue and then assembled these submodels into whole-body models. The disposition of fentanyl and alfentanil in the heart and brain and of fentanyl in the lungs could be described by perfusion-limited 1-compartment models. The disposition of both opioids in all other examined tissues was characterized by 2- or 3-compartment models. From these models, the extraction ratios of the opioids in the various tissues could be calculated, confirming the generally lower extraction of alfentanil as compared to fentanyl. Assembly of the single-tissue models resulted in a wholebody model for fentanyl that accurately described its disposition in the rat. A similar assembly of the tissue models for alfentanil revealed non first-order elimination kinetics that were not apparent in the blood concentration data. Michaelis-Menten parameters for the hepatic metabolism of alfentanil were determined by iterative optimization of the entire model. The parametric models were finally scaled to describe the disposition of fentanyl and alfentanil in humans. PMID- 7791039 TI - Estimation of sieving coefficients of convective absorption of drugs in perfused rat jejunum. AB - Intestinal absorption of many hydrophilic drugs cannot be explained solely in terms of pH-partition and solvent-drag effects have been described in a number of cases. However, quantitative estimates of sieving coefficient (phi) for drug molecules have tended to be variable. In the present work an in situ perfused intestinal loop preparation in the rat has been used to measure the disappearance of five hydrophilic drugs from the intestinal lumen and a mathematical model of drug absorption in the presence of net and unidirectional fluid fluxes has been developed. The model allows separate estimation of the convective (solvent drag) and nonconvective (partition) components of drug absorption from the experimental data. The five drugs studied were found to have phi values ranging from 0.1-0.9; this was highly dependent on molecular size. Analysis of the data shows that three of the drugs are absorbed almost exclusively by the convective process (caffeine, cimetidine, hydrochlorthiazide) while the other two are absorbed by both convective and nonconvective processes (salicylate, oxprenolol). We conclude that the methodology is a useful and reliable means of deriving separate estimates of these two components of drug absorption. PMID- 7791040 TI - Comparison of the Akaike Information Criterion, the Schwarz criterion and the F test as guides to model selection. AB - In pharmacokinetic data analysis, it is frequently necessary to select the number of exponential terms in a polyexponential expression used to describe the concentration-time relationship. The performance characteristics of several selection criteria, the Akaike Information Criterion (AIC), and the Schwarz Criterion (SC), and the F test (alpha = 0.05), were examined using Monte Carlo simulations. In particular, the ability of these criteria to select the correct model, to select a model allowing estimation of pharmacokinetic parameters with small bias and good precision, and to select a model allowing precise predictions of concentration was evaluated. To some extent interrelationships among these procedures is explainable. Results indicate that the F test tends to choose the simpler model more often than does either the AIC or SC, even when the more complex model is correct. Also, the F test is more sensitive to deficient sampling designs. Clearance estimates are generally very robust to the choice of the wrong model. Other pharmacokinetic parameters are more sensitive to model choice, particularly the apparent elimination rate constant. Prediction of concentrations is generally more precise when the correct model is chosen. The tendency for the F test (alpha = 0.05) to choose the simpler model must be considered relative to the objectives of the study. PMID- 7791041 TI - Refining analysis of refractive surgical outcomes. PMID- 7791042 TI - Standing while performing phacoemulsification. PMID- 7791043 TI - Impact of Salzmann's lesions on corneal curvature. PMID- 7791044 TI - In vitro test of intraocular lens biocompatibility. PMID- 7791045 TI - Potential pitfall in the safe use of the DuoTrak-style diamond knife. PMID- 7791046 TI - Using the intraocular lens cap for intraoperative qualitative keratometry. PMID- 7791047 TI - Consultation section. Suture erosion of posterior chamber intraocular lenses. PMID- 7791048 TI - Recognition and management of internal wound gape. AB - We describe a method for recognizing and managing wound gape of the internal aspect of a scleral tunnel incision. The apposition of the cataract internal incision can be adequately assessed with the use of a gonioprism during and after surgery. With self-sealing tunnel incisions, even though the external incision may be well sealed either with or without the use of a suture, the internal incision may be inconspicuously gaping. When an internal incision gapes open, it takes on the appearance of an elongated oval opening by gonioscopy, a process we have termed fishmouthing. Often fishmouthing can be closed by rapidly deepening the anterior chamber with balanced salt solution through the paracentesis incision; if this is unsuccessful, a limbal suture may be required. Assessment of the internal incision with a gonioprism and management of internal incision fishmouthing is an important method to ensure wound stability and minimize surgically induced astigmatism. PMID- 7791049 TI - A corneal lens/shield system to promote postoperative corneal epithelial healing. AB - We used a disposable bandage soft contact lens piggybacked onto a medicated, 12 hour corneal collagen shield to promote postoperative corneal epithelial healing and to provide sustained delivery of high levels of medications after corneal surgery in patients known to have poor corneal epithelial wound healing characteristics. Our experience with three patients indicates that the collagen shield dissolves completely by the first postoperative day and that the bandage lens remains in place with good mobility until it is removed when epithelialization is complete. This system eliminates the need for painful manipulation and placement of a bandage soft contact lens in an edematous, inflamed eye during the immediate postoperative period. PMID- 7791050 TI - Retinal detachment following intracapsular and extracapsular cataract extraction. AB - In 1984, our ophthalmology department switched from intracapsular cataract extraction (ICCE) to extracapsular cataract extraction (ECCE). We reviewed the postoperative incidence of retinal detachment (RD) in two consecutive series: (1) 604 eyes operated on by ICCE from 1982 to 1983 and (2) 1726 eyes operated on by ECCE from 1985 to 1986. Follow-up averaged 39 months in both groups. The RD incidence was 1.30% after ICCE and 0.41% after ECCE, a statistically significant difference. In both groups, the risk of RD was high for patients less than 70 years of age at the time of surgery but minimal for patients older than 70 years. The proportion of younger patients was significantly higher in the ICCE group (29.5%) than in the ECCE group (23.2%). When the data were stratified by age and the difference in age composition adjusted for statistically, the difference between the two groups in the incidence of postoperative RD was less pronounced. We conclude that although not significant at the 5% level after adjusting for age distribution, our results suggest a decreased risk of RD with ECCE. PMID- 7791051 TI - Incidence of retinal detachment after cataract surgery and neodymium: YAG laser capsulotomy. AB - The objective of this retrospective study was to determine the incidence of retinal detachment (RD) in patients following cataract extraction with intraocular lens placement and after neodymium:YAG (Nd:YAG) laser capsulotomy. This study comprised 1092 patients (1168 eyes) who had cataract extraction and related procedures between January 1986 and December 1992 identified from the coding and billing database. Of the 1092 patients, 215 (244 eyes) had had Nd:YAG laser capsulotomy. Their charts were reviewed for incidence of RD, and these data were correlated with age, sex, axial length, surgical complications, and other surgical procedures done at the time of cataract extraction. The incidence of RD following phacoemulsification alone was 0.75% (6/799), with a mean time between cataract extraction and RD of 11.6 months. The cases of RD after extracapsular cataract extraction, combined phacoemulsification and trabeculectomy, combined extracapsular cataract extraction and penetrating keratoplasty, and combined phacoemulsification and anterior vitrectomy were too few to draw any conclusions. The incidence of RD following Nd:YAG laser capsulotomy was 0.82% (2/244), with a mean time of 32 months between cataract surgery and capsulotomy and 13.5 months between capsulotomy and RD. There was a statistically significant higher incidence of RD after posterior capsule rupture and anterior vitrectomy than after uncomplicated phacoemulsification (2/12 versus 6/799). In conclusion, the rate of RD after uncomplicated phacoemulsification was less than or similar to the rate found in other recent studies. It was not statistically different from the rate following phacoemulsification and Nd:YAG laser capsulotomy (0.82%). This study confirms the increased risk of RD following posterior capsule rupture and anterior vitrectomy. PMID- 7791052 TI - Prospective study of cataract surgery, capsulotomy, and retinal detachment. AB - We report the incidence of retinal detachment (RD) in 1543 consecutive cases of cataract extraction in a prospective cohort study. Retinal detachment was significantly associated with intracapsular extraction, axial lengths of 24.0 mm or longer and an intact capsule, and capsulotomy in eyes with axial lengths of 24.0 mm or longer. The interval between capsulotomy and RD was significantly shorter in eyes with axial lengths of 24.0 mm or greater. An intraocular lens with stiff, vaulted, poly(methyl methacrylate) optics and a biconvex PMMA optic was associated with significantly less capsule opacification than lenses of other designs. PMID- 7791053 TI - Clinical evaluation of hexagonal keratotomy for the treatment of primary hyperopia. AB - We evaluated the effectiveness of spiral hexagonal keratotomy in correcting primary hyperopia in 199 eyes. One hundred eighty-four eyes (92.5%) had a minimum follow-up of three months. Mean follow-up was 11.9 months and maximum, 36.2 months. Secondary astigmatic keratotomy was performed on 54 eyes six to eight months after initial hexagonal surgery to correct induced astigmatism. The mean reduction in spherical equivalent was -1.6 +/- 0.9 diopters (D) (range -5.6 to +0.9 D). The mean increase in refractive cylinder was +0.5 +/- 0.9 D (range -2.3 to +3.0 D). Uncorrected acuity improved by +3.2 lines, while best corrected acuity decreased slightly by -0.26 lines. Loss of two or more lines of best corrected acuity that was attributable to surgery was between 0.5% and 4.0%. PMID- 7791054 TI - Excimer laser photorefractive keratectomy for myopia: six-month follow-up. AB - In this study, 108 eyes of 62 patients had photorefractive keratectomy (PRK) with a 193 nm excimer laser to correct myopia. The eyes were assigned to one of three groups: low, moderate, or high myopia. Six months after PRK, 88.9% of eyes in the low myopia group, 90.0% in the moderate myopia group, and 23.8% in the high myopia group achieved an uncorrected visual acuity of 20/40 or better. In the low myopia group, 88.9% were within +/- 1 diopter (D) of attempted correction, as were 70.0% in the moderate group and 18.8% in the high myopia group. There were no significant complications. We conclude that excimer laser PRK appears to be a safe and relatively accurate procedure to correct low to moderate myopia but not high myopia because of regression over time. PMID- 7791055 TI - Relative effectiveness of topical ketorolac and topical diclofenac on discomfort after radial keratotomy. AB - Two prospective, randomized, double-masked studies were conducted evaluating the analgesic effect of topical eyedrops after radial keratotomy (RK). One study of 117 consecutive initial RK procedures compared topical ketorolac (Acular) with topical diclofenac (Voltaren), and another study of 23 consecutive initial RK procedures compared topical ketorolac with a control medication (HypoTears). Topical ketorolac was significantly more effective than the control but not significantly different from topical diclofenac. The onset of analgesic effect of these topical nonsteroidal anti-inflammatory drugs is longer than one hour. The analgesic effect of oral acetaminophen #3 significantly augments that of topical diclofenac drops for those experiencing any discomfort by six hours after surgery. PMID- 7791056 TI - Preliminary report of sutureless phacotrabeculectomy through a modified self sealing scleral tunnel incision. AB - A method of combined cataract extraction and trabeculectomy using phacoemulsification through a modified 5 mm sutureless scleral tunnel incision is described. In eight patients who were followed for a minimum of five months in an initial series, the intraocular pressure (IOP) decreased to less than 19 mm Hg; six achieved this result at six months on no medication. The IOP decreased from a mean of 30.88 mm Hg preoperatively to 13.75 mm Hg at two months and 14.00 mm Hg at six months. The preoperative mean of 3.63 antiglaucoma medications per patient decreased to 0.25 postoperatively. Although all patients had advanced glaucomatous optic neuropathy with a preoperative mean cup/disc ratio of 0.79, visual acuity improved in six patients; four patients had an acuity of 20/40 or better at both one week and two months. Surgically induced astigmatism averaged 0.57 diopter (D) at two months, with a mean astigmatic shift of 0.08 D with the rule at two months and 0.41 D with the rule at three months. No hypotonous or flat anterior chambers were encountered; there were visible blebs in seven patients at six months. The sutureless phacotrabeculectomy preserves all the advantages of small incision phacoemulsification and appears to be a safe and effective combined procedure for IOP control in glaucoma patients with cataracts. PMID- 7791057 TI - Atonic pupil after cataract surgery. AB - We report and describe the clinical findings of three patients who developed atonic pupil after uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens implantation. All patients had normally reactive pupils one day postoperatively, but after two weeks, the pupils were dilated and nonreactive to light, accommodation, and miotics. To estimate the incidence of atonic pupil after cataract surgery, we sent a survey on the frequency, clinical features, and possible etiologies of this syndrome to members of the American Society of Cataract and Refractive Surgery. Of the 567 respondents, 60% had seen at least one case of atonic pupil in the past five years; they reported a total of 1543 cases during that time. This is probably a conservative figure since many cases undoubtedly go unnoticed because of a lack of visual disturbance. We believe this condition occurs more frequently than previously reported. The atonic pupil should be recognized as a possible complication of cataract surgery that should be included in the preoperative consent form. PMID- 7791058 TI - Cataract surgery outcomes: importance of co-morbidities in case mix. AB - Variation in patients' preoperative co-morbidities can have a significant effect on the outcomes of cataract surgery. To examine the effects of that variation, we did a retrospective study of the outcomes of extracapsular cataract surgery performed by seven surgeons. Medical records from 791 surgeries done from June 1, 1986, through May 31, 1989, were retrospectively examined. Variations in postoperative visual acuity and intraoperative and postoperative complications were documented. The relationships between preoperative ocular and systemic medical co-morbidities and postoperative visual results and complications were studied. A statistical model was developed to adjust for the preoperative co morbidity case mix between physicians. Visual acuity rates varied by surgeon and surgical volume, but not significantly when adjusted for patient case mix. PMID- 7791059 TI - Mechanism of iris prolapse: a qualitative analysis and implications for surgical technique. AB - A theoretical explanation of the mechanism of iris prolapse is presented using simple flow mechanics and the Bernouille principle, which states that fluid pressure varies inversely to fluid velocity. Rapid aqueous escape into an anterior chamber perforation thus creates a relative vacuum anterior to the iris. Further analysis shows that the tendency of the iris to prolapse into an anterior chamber wound increases as an inverse function of the fourth power of the radial distance between the iris and the perforation. Anterior wound placement, clear of the iris plane, should help to prevent iris prolapse. Minimizing the irrigation velocity (and hence the fluid outflow velocity) should also help to prevent intraoperative prolapse. PMID- 7791060 TI - Efficacy of diclofenac sodium solution in reducing discomfort after cataract surgery. AB - Two hundred consecutive patients were enrolled in a randomized, prospective clinical trial evaluating the efficacy of diclofenac sodium (Voltaren Ophthalmic) in reducing patient discomfort after cataract surgery. Other factors evaluated were the effect of preoperative flurbiprofen (Ocufen) in preventing intraoperative miosis and on postoperative discomfort and the effect of incision size and intraocular carbachol (Miostat) on postoperative comfort. Diclofenac significantly reduced discomfort during the first 24 hours after surgery but not two to three days postoperatively, although there was a trend toward reduction. Flurbiprofen given preoperatively did not affect postoperative discomfort. It also did not affect pupil size at the start of surgery but did reduce intraoperative miosis. Incision size (5.2 mm versus 7.0 mm) had no effect on discomfort. Miostat did not affect discomfort, although there was a trend toward more discomfort. The results indicate that topical diclofenac, given immediately after cataract surgery, significantly reduces discomfort during the first 24 postoperative hours. PMID- 7791063 TI - Contrast sensitivity, glare, and visual function: diffractive multifocal versus bilateral monofocal intraocular lenses. AB - We measured contrast sensitivity binocularly in different light conditions in nine patients with bilateral diffractive multifocal intraocular lenses (IOLs) and nine patients with bilateral monofocal IOLs. In general, the diffractive multifocal group had a lower mean contrast sensitivity. Patients completed a questionnaire that asked about their vision under daylight, twilight, and sunshine conditions. Monofocal patients had complete visual restitution in all light conditions. Multifocal patients reported several visual problems, especially when driving at night, but also in normal daylight and cloudy weather conditions. PMID- 7791062 TI - Comparative clinical trial of AMO Vitrax and Healon use in extracapsular cataract extraction. AB - This randomized, single-masked, multicenter clinical trial, comprising 95 patients enrolled at five sites, evaluated the performance of AMO Vitrax and Healon viscoelastic materials during cataract surgery. Patients were examined preoperatively and at one day, four days, one month, and three months postoperatively. The following measurements were recorded and analyzed: percentage of endothelial cell loss from preoperative to three months postoperative; change in intraocular pressure (IOP) from preoperative to 24 hours postoperatively; postoperative corrected visual acuity; subjective assessment of ability of viscoelastic to create and maintain tissue space; intraocular transparency; ease of evacuation. Three months postoperatively, endothelial cell loss was 4.9% (+/- 8.3%) for the AMO Vitrax group and 6.3% (+/- 10.5%) for the Healon group. One day postoperatively, IOP decreased by 1.6 mm Hg and increased by +1.1 mm Hg, respectively. Postoperative visual acuities were similar between the two groups at three months. Subjective assessment of transparency was higher for Healon. Assessment of tissue space maintenance was similar between the two materials. Healon was rated as slightly easier to evacuate. PMID- 7791061 TI - Effectiveness of apraclonidine and acetazolamide in preventing postoperative intraocular pressure spikes after extracapsular cataract extraction. AB - We studied the effectiveness of two prophylactic agents in controlling early postoperative intraocular pressure (IOP) increases after cataract surgery. Fifty four nonglaucomatous patients received either topical 1% apraclonidine, one drop before and after surgery, or sustained-release acetazolamide, 500 mg, or no medication at the completion of planned extracapsular cataract extraction (ECCE). Mean baseline IOPs were similar among patients randomized to the apraclonidine, acetazolamide, and control groups: 15.29 mm Hg, 15.33 mm Hg, and 14.26 mm Hg, respectively. At 3 hours postoperatively, IOPs were significantly lower in the apraclonidine group (11.13 mm Hg, P = .035), nonsignificantly lower in the acetazolamide group (13.3 mm Hg, P = .17), and significantly increased in the control group (21.32 mm Hg, P = .003). One eye in the apraclonidine group and six in the control group had IOPs greater than 30 mm Hg. At 24 hours, the only statistically significant difference was in the control group, whose mean IOPs remained elevated (21.83 mm Hg, P = .0008). One eye in the apraclonidine group, two in the acetazolamide group, and five in the control group had IOPs greater than 30 mm Hg. We found a significant early IOP reduction with apraclonidine given topically preoperatively and at the completion of planned ECCE. PMID- 7791065 TI - Innovator's lecture, 1994. Limitation, logic, and language. PMID- 7791064 TI - Postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. AB - We performed slitlamp microscopy and specular microscopy in 15 patients who had cataract surgery to determine the clinical course of postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. Membranous proliferation observed in 11 of the 15 eyes eventually resolved in 10 eyes. We speculate that lens epithelial cells were the origin of the membrane. PMID- 7791066 TI - Low-dose intraocular tissue plasminogen activator treatment for traumatic total hyphema, postcataract, and penetrating keratoplasty fibrinous membranes. AB - Tissue plasminogen activator (tPA) has been used to treat severe postcataract and vitrectomy fibrinous membranes, but intraocular bleeding has occurred with doses of 25 micrograms or higher. We report three patients, one with nonclearing total hyphema and uncontrollable intraocular pressure and two with severe fibrinous membrane formation, who had treatment with low-dose (4 micrograms to 6 micrograms) intraocular tPA. Although the fibrinous membranes or hyphema resolved in all three patients, they recurred and bleeding that required additional treatment occurred in one patient. Intraocular low-dose tPA may minimize the risk of corneal and retinal toxicity and may be considered an alternative treatment in intractable cases. However, secondary intraocular hemorrhage can occur, and the timing between the initial vascular injury, treatment with tPA, and subsequent bleeding may reduce the risk of further hemorrhaging. PMID- 7791067 TI - Corneal damage after glass intraocular lens implantation. AB - We present three cases of corneal damage in two patients after implantation of an anterior chamber, iris-supported, intraocular lens (IOL) with a glass optic and polyamide haptics. We found bullous keratopathy in all three eyes. Penetrating keratoplasty, IOL removal, and anterior vitrectomy were performed in all cases. We believe the bullous keratopathy was caused by long-term iritis and pseudophakodonesis. PMID- 7791069 TI - Different mechanisms mediated by dopamine D1 and D2 receptors are involved etiologically in activity-stress gastric lesion of the rat. AB - Rats subjected to activity-stress developed gastric lesions and showed excessive running activity with an increase of light/dark ratio. Daily treatment with centrally acting dopamine antagonists, SCH23390 [(R)-(+)-8-chloro-2,3,4,5 tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol] (0.1-10 mg/kg), haloperidol (0.1-10 mg/kg), sulpiride (32-320 mg/kg), clozapine (1-100 mg/kg) and metoclopramide (1-100 mg/kg) suppressed the lesion formation: ID50 values were 0.9, 0.4, 53, 8.9 and 60 mg/kg, respectively. On the other hand, domperidone (1 100 mg/kg), a peripherally acting dopamine antagonist, failed to suppress the lesion formation and FR64822 [N-(4-pyridylcarbamoyl)amino 1,2,3,6 tetrahydropyridine] (1-32 mg/kg), a central dopamine enhancer, aggravated it. The excessive running activity was reversed dose-dependently by treatment with haloperidol, a specific dopamine D2 antagonist, but not by SCH23390, a specific dopamine D1 antagonist. Conversely, the increased light/dark ratio was attenuated dose-dependently by SCH23390, but not by haloperidol. Neither antisecretory agents nor 5-hydroxytryptamine antagonists were effective against the lesion formation. These results suggest that an activation of central dopamine D1 and D2 receptors is responsible for the increased light/dark ratio and enhanced running activity, respectively, and that both of the changes are involved in the etiology of activity-stress induced lesions. PMID- 7791068 TI - Relaxing the fibrosed capsulorhexis rim to correct induced hyperopia after phacoemulsification. AB - I present two cases in which hyperopia occurred after phacoemulsification through a capsulorhexis. In both eyes, the anterior capsule rim had become fibrosed and contracted. The patients were successfully treated with YAG laser relaxing incisions. PMID- 7791070 TI - Receptor subtypes involved in dual effects induced by prostaglandin E2 in circular smooth muscle from dog colon. AB - Smooth muscle strips and isolated muscle cells from the circular layer of dog colon, were used to study the effect of prostaglandin E2 (PGE2) and their analogs acting at EP receptors: Iloprost (IP/EP1), butaprost (EP2) and enprostil (EP3) and SC19220 (antagonist EP1) to characterize the EP-receptors involved in the control of muscle function. In strips treated with tetrodotoxin, only enprostil provoked a concentration-dependent contraction. The concentration of enprostil inducing a half maximal contraction (EC50) was 400 nM and the maximal effect was obtained at 1 microM. PGE2, butaprost and iloprost induced a dose-dependent relaxation, with an EC50 of 200, 80 and 200 nM, respectively. The maximal relaxation was obtained at 1 microM for all these agents. When the EP1 antagonist, SC19220 (10 microM), was added 20 min before PGE2 or their analogs, their respective concentration-response curves were not affected. In isolated cells, PGE2 and enprostil induced a cell contraction in a concentration-dependent manner, whereas iloprost and butaprost had no effect by themselves. The maximal contraction was 241.1 +/- 1.7% at 10 nM PGE2 and 22.5 +/- 1.6% at 10 nM enprostil. EC50 of PGE2 and enprostil was 40 pM. SC 19220, at concentrations ranging from 1 pM to 0.1 microM, failed to inhibit the contraction induced by either PGE2 or enprostil. When cells were preincubated for 1 min with butaprost or iloprost at concentrations ranging from 1 pM to 1 microM, the contraction induced by CCK8 (10nM) was inhibited in a concentration-dependent matter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791071 TI - RP 73870, a gastrin/cholecystokinin-B receptor antagonist with potent anti-ulcer activity in the rat. AB - RP 73870, the racemic potassium salt of (([N-(methoxy-3-phenyl)-N-(N-methyl-N phenyl-carbamoylmethyl)- carbamoylmethyl]-3-ureido)-3-phenyl)-2-ethylsulfonate (RS) is a potent, reversible antagonist of both gastrin and cholecystokinin-B receptors in guinea pig and rat tissues. This compound is a potent inhibitor of pentagastrin-stimulated gastric acid secretion in the perfused rat stomach. RP 73870 also inhibits basal gastric acid secretion in the rat, although at doses higher than that required for inhibition of pentagastrin-stimulated gastric acid secretion. RP 73870 is a potent inhibitor of aspirin-induced gastric damage in the rat. In the prevention of aspirin-induced gastric damage, RP 73870, given p.o., was 10-fold less potent than when given i.v. RP 73870 was as potent as a H2 receptor antagonist or proton pump inhibitor in the prevention of cysteamine induced duodenal ulcers in the rat. Relative to other gastrin/cholecystokinin-B antagonists, RP 73870 demonstrates greater affinity to gastrin binding sites, and possesses a unique spectrum of in vivo biological activities appropriate for an anti-ulcer indication. PMID- 7791072 TI - Anticonvulsant efficacy/safety properties of 2-amino-N-(1,2 diphenylethyl)acetamide hydrochloride. AB - 2-Amino-N-(1,2-diphenylethyl)-acetamide-hydrochloride (FPL 13950) was profiled preclinically in rodents for efficacy against convulsions, as well as for acute safety/behavioral observations. FPL 13950 exhibited good oral efficacy and duration of action with respect to prevention of seizures elicited by maximal electroshock-shock in both rats and mice. Tolerance to protection against maximal electroshock and hexobarbital-induced sleep-time was not evident after subchronic drug administration. FPL 13950 also prevented convulsions/mortality in mice after i.v. dosing with N-methyl-D, L-aspartate, however, it was ineffective against other types of chemically induced convulsions, as well as bicorneal kindling. High oral doses produced neural impairment in both mice and rats and hyperactivity in rats. Sequential administration of yet higher doses elicited tonic/clonic convulsions culminating in death. During i.v. infusion of metrazol in mice, high i.p. doses of FPL 13950 shortened the latency to first twitch and clonus. No increase in the startle response or phencyclidine-like behavior was evident after oral dosing in rats. PMID- 7791074 TI - Effect of intracerebroventricular beta-funaltrexamine on mu opioid receptors in the rat brain: consideration of binding condition. AB - Effects of 24 h pretreatment with intracerebroventricular (icv) beta funaltrexamine (beta-FNA) on brain opioid receptor binding in rats were examined under various conditions. Agonist binding to mu and delta opioid receptors (with [3H][[cap]dAla2,MePhe4,Gly-ol5]enkephalin (DAMGO)[3H][D-Pen2, D-Pen5]enkephalin (DPDPE), respectively) was performed under three different conditions: i) pretreatment of membranes with GDP and Na+ and binding in the presence of Mg++ in Tris-HCI buffer containing EGTA and leupeptin for 1.5 to 3 h; ii) binding in Tris HCI buffer containing bacitracin, leupeptin, chymostatin and bestatin for 3 to 4 h; iii) binding in Tris-HCI buffer containing EGTA and leupeptin for 45 min. Condition i was shown to convert opioid receptors to a high affinity state for agonists. beta-FNA (2, 6 or 20 nmol) significantly reduced 1 nM [3H]DAMGO binding in the whole brain with i but not with ii. With iii, 20 nmol beta-FNA reduced [3H]DAMGO binding, but not 2 or 6 nmol. Saturation experiments with i showed that the reduction in [3H]DAMGO binding after 6 or 20 nmol beta-FNA was due to a decrease in Bmax and an increase in KD. For delta binding, there was no significant change in [3H]DPDPE (2 nM) binding with i after 2, 6 or 20 nmol beta FNA. Thus, under i, icv beta-FNA reduced [3H]DAMGO binding significantly without affecting [3H]DPDPE binding. In addition, mu binding was also conducted with 1 nM [3H]naloxone under three different conditions: iv) in the presence of Na+ and GDP; v), in the presence of Na+, Gpp(NH)p and Mg++; vi) in the presence of Na+. Both iv and v were shown to shift opioid receptors to a low affinity state for agonists. beta-FNA (20 nmol) significantly decreased 1 nM [3H]naloxone binding under each of the three conditions. Competitive inhibition of 1 nM [3H]naloxone binding by DAMGO in the presence of Na+ and GDP showed that receptors existed in a single low affinity state for DAMGO, and that icv beta-FNA caused a reduction in Bmax without affecting the KD of DAMGO. In summary, when all the receptors were converted to a high agonist affinity state i or a low agonist affinity state iv, the changes in mu binding induced by beta-FNA could be revealed with agonist binding. Additionally, changes in mu binding induced by beta-FNA could be detected with [3H]naloxone, which always displayed high affinity regardless of agonist affinity states, under each of the three conditions (iv, v and vi). PMID- 7791073 TI - Modulation of the activity of central serotoninergic neurons by novel serotonin1A receptor agonists and antagonists: a comparison to adrenergic and dopaminergic neurons in rats. AB - In this study, we used a complementary in vivo electrophysiological and (in individual rats) neurochemical approach to characterize the actions of chemically diverse serotonin (5-HT)1A receptor ligands at central 5-HT1A autoreceptors as compared to dopamine (DA) D2 autoreceptors and presynaptic alpha-2 adrenergic receptors (ARs). The novel, high efficacy, 5-HT1A agonists, WY 48,723 (an arylpiperazine), (+)-flesinoxan (a benzodioxane) and S 14671 and S 14506 (methoxynaphtylpiperazines) mimicked the aminotetralin, 8-hydroxy-2-(di-n propylamino)tetralin hydrobromide (8-OH-DPAT), in inhibiting the firing of dorsal raphe nucleus (DRN) neurons. Similarly, the firing rate of DRN neurons was reduced by the "partial" agonists, MDL 73005EF, BMY 7378, NAN-190, tandospirone and the novel pyrimidinylpiperazine, zalospirone. Furthermore, S 14489, S 15535 and S 15931, novel benzodioxopiperazines, which behave as antagonists at postsynaptic 5-HT1A receptors, inhibited completely DRN firing, whereas the methoxyphenylpiperazine, WAY 100,135, and the aryloxoarylamine, (-)-tertatolol, were ineffective. Indeed, in analogy to spiperone, both WAY 100,135 and (-) tertatolol behaved as apparently competitive antagonists in that, in their presence, the dose-response curves for inhibition of DRN firing by S 14671, S 14506 or 8-OH-DPAT were shifted in parallel to the right with no loss of maximal effect. In distinction to WAY 100,135 and (-)-tertatolol, a further novel, putative "antagonist," SDZ 216-525 (a benzoisothiazolpiperazine) weakly inhibited the electrical activity of the DRN. With the exception of (-)-tertatolol, which behaved as a weak agonist, a very similar pattern of inhibition of 5-HT turnover was seen in the striatum (innervated by the DRN), the hippocampus and the hypothalamus (DRN and median raphe nucleus) and the spinal cord (nucleus raphe magnus), with the striatum displaying the greatest sensitivity. Drug potency for inhibition of firing and turnover was highly correlated (r = 0.80-0.82) and these actions were significantly correlated to affinity at (hippocampal) 5-HT1A receptors (r = 0.62-0.73). As concerns DA D2 autoreceptors, the agonist action of apomorphine in reducing DA turnover were mimicked only by 8-OH-DPAT, whereas the majority of the other 5-HT1A ligands, in analogy to raclopride, enhanced DA turnover. The facilitation of DA turnover appeared to reflect direct blockade of DA D2 autoreceptors because potency was correlated powerfully to affinity at these D2 sites (r = 0.89).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7791075 TI - Spinal nonadrenergic imidazoline receptors do not mediate the antinociceptive action of intrathecal clonidine in the rat. AB - The intrathecal administration of clonidine to rats results in profound antinociception which is thought to be mediated through an interaction of the agonist with spinal alpha-2 adrenergic receptors. However, clonidine has been shown to also interact with nonadrenergic imidazoline receptors. Consequently, this study was undertaken to determine if nonadrenergic imidazoline receptors are present in the rat spinal cord, and the extent to which they are involved in the antinociceptive action of spinally administered clonidine. By using the tail flick test, the antinociceptive action of spinally administered clonidine was found to be blocked completely by the intrathecal administration of the imidazoline idazoxan. Similarly, yohimbine (a nonimidazoline alpha-2 adrenergic antagonist) also blocked completely the antinociceptive action of clonidine. Results of radioligand binding studies demonstrated that norepinephrine did not interact with approximately 20% of all specific spinal sites labeled by 4 nM [3H]clonidine, indicating the presence of nonadrenergic spinal sites. Affinity data obtained from competition binding assays demonstrated that the spinal nonadrenergic sites labeled by [3H]clonidine possess little affinity for yohimbine. Therefore, nonadrenergic imidazoline receptors are not involved in the antinociceptive action of spinally administered clonidine. PMID- 7791076 TI - Modulation of methylenedioxymethamphetamine-induced striatal dopamine release by the interaction between serotonin and gamma-aminobutyric acid in the substantia nigra. AB - The effects of the amphetamine analog, 3,4-methylenedioxymethamphetamine (MDMA) were compared to the effects of d-amphetamine on the in vivo release of dopamine and gamma-aminobutyric acid (GABA) in the striatum and substantia nigra. The brain region-dependent role of the 5-HT2 receptors in the striatum and substantia nigra in regulating MDMA-induced dopamine and GABA release also was studied. Changes in the extracellular concentration of dopamine, 5-HT and GABA were measured simultaneously in the awake rat by in vivo microdialysis. The increase in striatal dopamine produced by systemic administration of MDMA was attenuated by infusion of TTX into the striatum. Infusion of the 5-HT2A/2C antagonist ritanserin into the striatum or the ipsilateral substantia nigra also significantly attenuated MDMA-induced dopamine release in the striatum. At the doses used in this study, MDMA but not d-amphetamine increased the extracellular concentrations of 5-HT and decreased GABA efflux in the substantia nigra. The ability of MDMA to decrease nigral GABA efflux also was blocked by the local infusion of ritanserin into either the substantia nigra or the striatum. Overall, these data provide evidence that MDMA increases dopamine release partly through an impulse-mediated mechanism. Furthermore, this increase in striatal dopamine efflux produced by MDMA is regulated, in part, by 5-HT2A/2C receptors in the striatum and the substantia nigra and ultimately by GABAergic input into the substantia nigra. PMID- 7791077 TI - S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) is a potent and long acting bradykinin B2 receptor antagonist, in vitro and in vivo. AB - The in vitro and in vivo effects of S 16118 [p-guanidobenzoyl-[Hyp3, Thi5,D Tic7,Oic8]bradykinin (BK)], a new BK receptor antagonist, were studied. S 16118 inhibited the contraction produced by BK in the rabbit jugular vein, but was ineffective in the rabbit aorta, indicating the BK B2 receptor specificity of the compound. In isolated organs from various species including humans, S 16118 was a potent antagonist (Ki, pA2 or pKB value from 9.58-7.37). The effect of S 16118 was specific as it did not show any affinity for a number of other receptors or channels and did not possess residual agonistic properties in most of the tissues studied. Furthermore, S 16118 is a poor secretagogue agent either in the rat or human mast cells and is resistant to degradation with an in vitro half-life in blood from different species, including humans, of more than 24 hr. In vivo, in the rabbit, i.v. injection of S 16118 inhibited the hypotension induced by BK up to 4 hr after administration. In the guinea pig, it was also effective in inhibiting the bronchoconstriction induced by BK, although when administered i.v. it had a shorter duration than in the rabbit. However, in the same species, when aerosolized, S 16118 was effective and long-acting against BK-induced bronchoconstriction. Changes in permeability induced by BK injection in the guinea pig trachea and bronchus, and by BK superfusion in the hamster cheek pouch, were abolished by i.v. pretreatment with S 16118.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791078 TI - Effects of the bradykinin B2 receptor antagonist S 16118 (p-guanidobenzoyl [Hyp3,Thi5,D-Tic7,Oic8]bradykinin) in different in vivo animal models of inflammation. AB - The effects of S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (BK)], a new, potent and long-acting BK B2 antagonist, were tested in some in vivo models of inflammation. In rats, S 16118 (0.1 and 1 mg/kg) given i.v. or s.c. delayed the edema formation induced by intraplantar carrageenan injections up to 4 hr after administration, confirming the involvement of kinins in this inflammatory reaction. In guinea pigs treated with atropine, vagal stimulation induced bronchial microvascular leakage. Aerosolization of S 16118 (5 x 10(-3) M for 20 sec), 4 min before vagus nerve stimulation, induced a 60% decrease in the Evans blue extravasation, demonstrating the modulatory role of BK in neurogenic inflammation. In rats, caerulein infusion (4 nmol/kg/hr) induced hypotension, massive pancreatic edema, hypovolemia due to plasma leakage and an increase in serum lipase and amylase activity. S 16118 (100 nmol/kg s.c.) prevented the hypotension, the pancreatic edema and the hypovolemia and induced a marked increase in the serum lipase and amylase activity. This confirms that BK, acting on BK B2 receptors, is involved in this model of pancreatitis. In rabbits, the injection of lipopolysaccharides (LPS; 600 micrograms/kg i.v.) induced hypotension, metabolic acidosis and leukopenia. S 16118 (1.73 mumol/kg i.v.) did not influence the effects of LPS injection. In mice, i.p. LPS (25 mg/kg) administration induced over 90% mortality in 96 hr. S 16118 (1 mg/kg x 4), given 30 min before LPS injection and 4, 8 and 24 hr after LPS injection, did not influence the mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791079 TI - Effects of caffeine on ventilation during acute and chronic nicotine administration in rhesus monkeys. AB - This study characterized the effects of caffeine (1.0-30.0 mg/kg) and nicotine (0.1-3.0 mg/kg) administered alone and in combination on ventilation in unanesthetized rhesus monkeys. In seated monkeys prepared with a head plethysmograph, ventilation was measured during exposure to air (normocapnia), CO2 (3%, 4% and 5%) mixed in air (hypercapnia), 10% O2 mixed in N2 (hypoxia) and 100% O2 (hyperoxia). Caffeine produced marked, dose-dependent increases in ventilation during conditions of normocapnia and hypercapnia. In contrast, acute administration of nicotine had less pronounced respiratory-stimulant effects during all conditions. The joint effects of caffeine and nicotine on ventilation generally did not differ from those obtained with caffeine alone. Chronic administration of nicotine (1.0 mg/kg/day) for 4 consecutive wk via osmotic pumps significantly decreased the half-life of caffeine but had little effect on ventilation or on sensitivity to the respiratory-stimulant effects of caffeine. Two primary metabolites of caffeine, theophylline and paraxanthine, were active as respiratory stimulants and were equipotent to caffeine, and the joint effects of caffeine and its metabolites were additive. The results indicate that caffeine and nicotine stimulate respiration through different pharmacological mechanisms, in contrast to caffeine and its metabolites which exhibit a similar pharmacological profile. Moreover, significant pharmacokinetic interactions may be obtained when caffeine and nicotine are coadministered. PMID- 7791081 TI - Antiproliferative effects of delta opioids on highly purified CD4+ and CD8+ murine T cells. AB - Numerous studies have shown that opioids modulate the proliferative response of mixed splenocytes to T cell mitogens. To identify the T cell subpopulations affected by opioids, splenocytes from C57BL/6 and CD1 mice were separated using a fluorescent activated cell sorter (FACS) to obtain 98 to 99% pure populations of either CD4+ or CD8+ T cells. Cells were stimulated to proliferate in serum-free medium by cross-linking the T cell receptor using plate-coated anti-CD3-epsilon, then 3H-thymidine uptake and cell number were measured at 48 and 72 hr. [D-Ala2] deltorphin 1 (deltorphin) dose-dependently inhibited the proliferation of C57BL/6 CD4+ T cells by approximately 50%. This effect was maximal when cells were preincubated with deltorphin 60 min before activation, whereas deltorphin was ineffective when added at the time of activation. Similarly, [D-Ala2]-Met Enkephalinamide (DAME) 10(-11) to 10(-7) M inhibited CD4+ T cell proliferation. Naltrindole 10(-12) M abolished the antiproliferative effect of 10(-7) M deltorphin on CD4+ T cells. Proliferation of CD8+ T cells from C57BL/6 mice also was dose-dependently inhibited by deltorphin. At all concentrations to deltorphin, the antiproliferative effects were greater after 48 compared to 72 hr in culture. The effect of deltorphin and DAME on secretion of the T cell growth factor, IL-2, was determined by ELISA analysis of supernatants obtained from CD4+ T cells after 48-hr culture. Deltorphin showed a biphasic effect: 10(-11) M enhanced IL-2 secretion, whereas higher concentrations (10(-9)-10(-7) M) were inhibitory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791080 TI - Effects on atrial repolarization of the interaction between K+ channel blockers and muscarinic receptor stimulation. AB - We have tested, in guinea pig atria, how muscarinic stimulation by oxotremorine (Oxo) modifies the effects on action potential duration (APD) of two iK blockers: d-sotalol (5 microM) and ambasilide (1 microM). APD was prolonged by d-sotalol (+34.8 +/- 2.9%) and ambasilide (+54.2 +/- 5.5%). Simultaneous superfusion with Oxo 0.5 microM markedly shortened APD; this effect was larger in the presence of d-sotalol than in the presence of ambasilide (-69 +/- 2% vs. -37.4 +/- 5%; P < .05). Moreover ambasilide, but not d-sotalol, antagonized APD shortening induced by Oxo. The basis for such a difference between the two drugs was studied in patch-clamp experiments on isolated rabbit atrial and sinoatrial myocytes. Besides blocking iK (half-effective concentration: EC50 = 2 microM), ambasilide almost completely inhibited iKACh (-86 +/- 2% at 10 microM; EC50 = 1.6 microM), which was minimally affected by d-sotalol. Ambasilide 2 microM increased 10-fold the acetylcholine (ACh) required for 50% iKACh activation, and reduced maximally activated iKACh by 18.8 +/- 6.3%. When iKACh was activated through a receptor independent mechanism, 10 microM ambasilide reduced this current by only 18.7 +/- 1.4% of its control value. Moreover, ambasilide, although not affecting the current i(f), in basal conditions, reversed its inhibition by ACh. Thus, 1) the effect of K+ channel blockers on atrial APD may be blunted by ACh; ambasilide effects are less sensitive to ACh than those of d-sotalol; 2) ambasilide, but not d-sotalol, inhibits iKACh; this probably occurs largely, although not exclusively, through muscarinic receptor antagonism. Inhibition of iKACh may account for the persistence of the effects of this drug on atrial APD despite muscarinic stimulation. PMID- 7791082 TI - Polymeric delivery of the active isomer of misoprostol reduces systemic availability and uterotonic activity. AB - SC-30249 is the active isomer of misoprostol responsible for its mucosal protective effects against nonsteroidal anti-inflammatory drugs (NSAIDS). Linkage of SC-30249 to a polybutadiene polymer results in a delivery system (SC-55307) that releases the active component only under the acidic conditions of the stomach. This approach could be used to minimize side effects and systemic availability of synthetic prostaglandins. These studies were done to determine whether uterotonic activity could be recorded after treatment with SC-55307. Female beagles were implanted with uterine strain gauge force transducers, allowed 10 days for recovery and treated with estrogen to sensitize the uterus to the actions of prostaglandins. Base-line responses were determined with SC-30249, i.v., and then a randomized series of four treatments were given: SC-30249, IG, 10 micrograms/kg; SC-55307, IG, equivalent to 30 and 100 micrograms/kg of SC 30249; and a blank polymer control. HCI was given IG to provide an acid environment in the stomach, uterine responses were obtained for up to 4 h and plasma concentrations of SC-30249 free acid was determined. No uterotonic effect was seen after a low dose of SC-55307, whereas the high dose caused a brief but statistically significant increase equal to 8.8% and 17.8% of the responses to SC 30249, i.v. and IG, respectively. Peak plasma levels of SC-30249 free acid were 176.4 +/- 17.4 and 59.5 +/- 10.6 pg/ml after SC-30249, i.v. and IG, respectively, but were only 3.9 +/- 1.7 and 15.5 +/- 6.6 pg/ml after low and high doses of SC 55307, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791083 TI - Modulation of the 5-hydroxytryptamine4 receptor-mediated response by short-term and long-term administration of corticosterone in rat CA1 hippocampal pyramidal neurons. AB - Corticosterone (CT) treatment decreases the magnitude of the 5-hydroxytryptamine (5-HT)1A receptor-mediated hyperpolarization in rat CA1 hippocampal pyramidal neurons. In the present study, we examined the short- and long-term effects of CT on the functionally excitatory 5-HT4 receptor-mediated decrease in the amplitude of the slow afterhyperpolarization (sAHP) that follows a calcium spike and the concomitant decrease in sAHP half decay time. Rats were adrenalectomized (ADX) 2 weeks before the experiment. Data for concentration-response curves were obtained with sharp electrode current clamp recordings in the CA1 pyramidal cell layer of hippocampal slices. Significant changes were found in the 5-HT4 receptor-mediated decrease in sAHP amplitude. The Emax of the 5-HT4 response was significantly increased in cells from ADX rats when the superfusion medium contained 1 nM CT. Short-term administration of 100 nM CT did not alter the 5-HT4 response. Chronic treatment with low concentrations of CT decreased the Emax of the 5-HT4 response. Treatment with CT concentrations that mimic conditions of chronic stress decreased the Emax of the 5-HT4 response and shifted the EC50 to the right. Based on these results we conclude that the magnitude and the potency of the 5-HT4 receptor-mediated decrease in sAHP amplitude is altered by CT. Because the short- and long-term effects of CT treatment are not the same, the actions of CT are time and concentration dependent. CT modulation of the 5-HT4 response is different from its modulation of the 5-HT1A response. PMID- 7791084 TI - Serotonin potentiates ethanol-induced excitation of ventral tegmental area neurons in brain slices from three different rat strains. AB - Neurons of the ventral tegmental area of Tsai (VTA) are important in mediation of the rewarding effects of drugs of abuse, including ethanol. We have demonstrated previously that ethanol excites neurons of the VTA recorded in a brain slice preparation. In the present study, we tested the interaction between serotonin and ethanol on putative dopamine neurons of the VTA. As reported previously, ethanol (20-160 mM) excited VTA neurons in a concentration-dependent manner. Serotonin (1-50 microM) produced only minor increases or decreases of the firing rate. In the presence of serotonin, the potency of ethanol was increased significantly. This potentiation of ethanol excitation by serotonin was seen in VTA slices taken from Sprague-Dawley, Fischer 344 and Lewis rats. The effect of 160 mM ethanol on VTA neurons from Fischer 344 rats, for example, was increased from 38.5 +/- 6.1% before serotonin to 77.4 +/- 16.7% after administration of 10 microM serotonin. Two serotonergic agonists, (+/-)-2,5-dimethoxy-4 iodoamphetamine hydrochloride and alpha-methylserotonin, also potentiated the ethanol-induced excitation. The action of serotonin to increase the potency of ethanol to excite VTA neurons may be an important factor in the rewarding effects of ethanol, and might be exploited to develop effective pharmacotherapeutic agents for the treatment of alcohol craving. PMID- 7791085 TI - Pharmacological characterization of SB 202235, a potent and selective 5 lipoxygenase inhibitor: effects in models of allergic asthma. AB - The peptidoleukotrienes and leukotriene B4, formed from arachidonic acid through the action of 5-lipoxygenase (5-LO), exert a spectrum of biological effects. It has been proposed that potent and selective 5-LO inhibitors will be effective therapy in diseases in which the peptidoleukotrienes and leukotriene B4 have been implicated, such as asthma and arthritis. The novel compound (S)-N-hydroxy-N-(2,3 dihydro-6-phenylmethoxy-3-benzyofuranyl )urea (SB 202235) was evaluated as a selective inhibitor of 5-LO in a cell-free system as well as in various cellular assays. In addition, the potential therapeutic value of SB 202235 was assessed in preclinical models of allergic asthma. The activity of the 5-LO enzyme isolated from rat basophilic leukemia-1 cells was inhibited by SB 202235 in a concentration-dependent manner with an IC50 value of 1.9 microM. Consistent with its ability to inhibit 5-LO, SB 202235 inhibited the production of leukotriene B4 by human monocytes and in human whole blood (IC50 values of 1.5 microM and 1.1 microM, respectively). The selectivity of SB 202235 was confirmed by its lack of effect against several other enzymes and receptors. SB 202235 potently and effectively inhibited the contraction produced by a single concentration of ovalbumin in guinea pig trachea (IC50 = 20 microM) and of anti-IgE in human bronchus (IC50 = 2 microM). SB 202235 (3-30 microM) also inhibited the contraction of guinea pig trachea in response to increasing concentration of ovalbumin. When administered orally (30 mg/kg) to conscious guinea pigs, SB 202235 attenuated antigen-induced broncho-constriction and the subsequent eosinophil influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791086 TI - Cytochrome P-450 2E1 is not the sole catalyst of chlorzoxazone hydroxylation in rat liver microsomes. off. AB - The contribution of individual cytochrome P-450 isozymes in the hydroxylation of the centrally acting skeletal muscle relaxant chlorzoxazone was determined in rat liver microsomes. The hydroxylation rate of chlorzoxazone was found to be 50% greater in male than female microsomes. Kinetic studies using control male microsomes showed that chlorzoxazone hydroxylation was biphasic with a calculated low Km (33 microM) and high Km (116 microM). Liver microsomes from isoniazid-, beta-naphthoflavone- or dexamethasone-treated male rats produced a Km of 93, 69 and 26 microM, respectively. When chlorzoxazone hydroxylation activity was measured at a high substrate concentration (200 microM), treatment of male rats with isoniazid, acetone, beta-naphthoflavone and dexamethasone produced increases in the activity rate of 124%, 117%, 81% and 32%, respectively. However, when the activity was measured at a low substrate concentration (2 microM), liver microsomes from dexamethasone-treated male and female rats produced 5- and 10 fold induction, respectively. In immunoinhibition studies at 200 microM of chlorzoxazone, antibodies specific for cytochrome P-450 2E1 inhibited the rate of chlorzoxazone hydroxylation in microsomes from control and isoniazid-treated male rats by 68% and 79%, respectively. A monoclonal antibody (C8) against P-450 1A1 inhibited 67% of the activity in microsomes from beta-naphthoflavone-treated male rats but was ineffective inhibiting chlorzoxazone hydroxylation in microsomes from control or dexamethasone-treated male rats. In liver from control female rats, antibodies against cytochrome P-450 2E1 inhibited 80% of chlorzoxazone hydroxylation, whereas it inhibited only 47% of the activity in dexamethasone treated females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791087 TI - Role of medullary I1-imidazoline and alpha 2-adrenergic receptors in the antihypertensive responses evoked by central administration of clonidine analogs in conscious spontaneously hypertensive rats. AB - The antihypertensive action of clonidine analogs are generally ascribed to stimulation of medullary alpha 2-adrenergic receptors. Several recent studies have implicated the newly characterized class of imidazoline receptors as playing a more important role in this regard. In this study, a series of doses of four imidazoline and two nonimidazoline antihypertensive drugs were administered by intracisternal (i.c.) injection to freely moving spontaneously hypertensive rats. All six drugs produced a dose-dependent fall in mean arterial pressure (MAP) and heart rate (HR). The most potent agents in lowering MAP were the imidazoline agents, particularly moxonidine, a drug that has high affinity for I1-imidazoline receptors, but relatively low affinity for alpha 2-adrenergic receptors. There was a high correlation between the apparent binding affinity (Ki) for I1 receptors on membranes derived from bovine rostral ventrolateral medulla and the relative potency for lowering MAP after i.c. injection in spontaneously hypertensive rats. In contrast, no correlation existed between binding affinity values for alpha 2-adrenergic receptors derived from the same source and the antihypertensive response. The results of these experiments are consistent with a role for medullary I1-imidazoline receptors in mediating the antihypertensive action of clonidine and related imidazoline compounds in conscious hypertensive animals. The nonimidazoline agent, guanfacine, although a clinically effective antihypertensive agent, was not efficacious after i.c. injection. This discrepancy may be explained by an opposing pressor action or by a depressor action mediated by alpha 2-adrenergic receptors at an alternate site when the drug is peripherally administered. In contrast, the other nonimidazoline antihypertensive agent azepexole was fully efficacious after i.c. injection of the highest doses. Further studies may be necessary to determine whether drugs such as azepexole have a receptor target other than I1 or alpha 2-adrenergic receptors. We conclude that antihypertensive efficacy within the lower brainstem of conscious animals is predicted by interaction with I1-imidazoline but not alpha 2-adrenergic receptors. PMID- 7791089 TI - Pharmacodynamics of 15(S)-hydroperoxyeicosatetraenoic (15-HPETE) and 15(S) hydroxyeicosatetraenoic acid (15-HETE) in isolated arteries from guinea pig, rabbit, rat and human. AB - The vasoactive properties of 15(S)-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15(S)-hydroxyeicosatetraenoic acid (15-HETE) were characterized in aortic rings of guinea pig (GPA), rat (RA) and rabbit (RbA), as well as pulmonary arteries from guinea pigs (GPPA) and humans (HPA). Four distinct patterns of activity were identified: 1) Cyclooxygenase-dependent relaxation (in GPA, GPPA and HPA). This could be speculated to be due to release of prostaglandin I2 or to conversion of 15-H(P)ETE to another vasorelaxant eicosanoid(s). The endothelium was the main source of this activity in GPA but not in HPA. 2) Cyclooxygenase independent relaxation mediated by both endothelium and the smooth muscle proper (only in RA). 3) Endothelium-dependent contraction associated with the release of unknown factor(s) (in GPA, GPPA and HPA). 4) Endothelium-independent contraction (in RbA). Nitric oxide was not involved in the relaxation of GPA and RA, nor was endothelin in the contraction of GPA. 15-HPETE and 15-HETE always elicited analogous responses in the same preparations, probably because of rapid metabolism of 15-HPETE into 15-HETE or, even more likely, because both eicosanoids have identical modes of action. We concluded that depending on factors such as the species, the dose of the compounds and the presence of other vasoregulators, the overall response to 15-HPETE or 15-HETE may be vasodilation or vasoconstriction. In addition, the type of responses elicited with 15-HPETE and 15-HETE in RbA and RA differed conspicuously from those expressed in GPA, GPPA and HPA. PMID- 7791088 TI - Evaluation of cannabinoid receptor binding and in vivo activities for anandamide analogs. AB - Recent evidence implicates anandamide as the endogenous ligand for the cannabinoid receptor. One purpose of this study was to determine the structural requirements for anandamide's receptor interaction and the influence of phenylmethylsulfonyl fluoride (PMSF), an enzyme inhibitor, on receptor affinity. A second objective was evaluation of the correlation between affinities of the analogs and in vivo pharmacological activities. The ability of anandamide and analogs to displace [3H]CP-55,940 ([3](-)-3-[2-hydroxyl-4-(1,1 dimethylheptyl)phenyl]-4-[3- hydroxylpropyl]cyclohexan-1-ol) was determined by a filtration assay. Displacement curves for anandamide in the presence of PMSF produced a Ki of 89 +/- 10 nM; without PMSF the Ki increased to 5400 +/- 1600 nM. Anandamide analogs were evaluated for their ability to produce antinociception and hypomotility. The levels of saturation of the anandamide structure were critical to receptor affinity and in vivo potency, with complete saturation and hydroxyl substitution with a fluorine moiety resulting in a compound with increased potency in the spontaneous activity and antinociception assays. Substitution of the hydroxyl with a fluorine atom increased affinity only in the presence of PMSF and reduced potency in the antinociception assay. Ethanolamide substitution with bromobenzenesulfonamide produced an inactive compound in all assays. Increasing the length of the N-substituent by one or two carbons decreased receptor binding affinity and potency in the tail-flick assay only. Certain structural modifications, such as methylations, allowed the analogs to retain affinity without the addition of PMSF. Linear correlation between the behavioral and binding assays were performed, and the greatest correlation was obtained with compounds that were either very potent or inactive. PMID- 7791090 TI - Effects of cicletanine on kidney function. 1. Clearance and micropuncture studies in anesthetized rats. AB - The purpose of our study was to analyze the effect of cicletanine on kidney function by using clearance and free flow micropuncture techniques in anesthetized rats. In the clearance experiments, cicletanine was tested at three different doses (15, 30 and 60 mg/kg i.v.). The drug dose-dependently increased urine flow, and urinary sodium and chloride excretion. Renal potassium excretion was also significantly enhanced. Cicletanine was as effective as hydrochlorothiazide regarding fractional renal sodium excretion. Mean arterial blood pressure fell after cicletanine at doses of 30 and 60 mg/kg, but at none of the three doses tested did cicletanine affect renal plasma flow and glomerular filtration rate. In this regard it differed from hydrochlorothiazide which was found to markedly decrease glomerular filtration rate at a dose of 10 mg/kg i.v. A coadministration of cicletanine (20 mg/kg i.v.) and hydrochlorothiazide, at a maximal effective dose (20 mg/kg i.v.), induced an additional diuretic and saluretic effect. By puncturing of late proximal, early and late distal nephron segments, an action of cicletanine (30 mg/kg i.v.) in the superficial distal tubule could be established. Thus, cicletanine shares with the thiazide diuretics its tubular site of action despite the disparity in chemical structure between these drugs. PMID- 7791092 TI - The effects of anorectic and aversive agents on deprivation-induced feeding and taste aversion conditioning in rats. AB - We compared the effects of intraperitoneally administered LiCl (0.5-2830 mumol/kg), sulfated cholecystokinin26-33 (10-1000 nmol/kg; CCK-8), nonsulfated CCK-8 (500 and 1000 nmol/kg), sulfated CCK26-29 (500 and 1000 nmol/kg), CCK30-33 (10-1000 nmol/kg) bombesin (10-1000 nmol/kg; BOM), (dl) fenfluramine HCl (0.9 37.3 mumol/kg; fenfluramine), fluoxetine HCl (2.9-86.7 mumol/kg; fluoxetine), and d-amphetamine sulfate (0.27-10.9 mumol/kg; AMPH) on both 18-hr deprivation induced feeding and one-bottle, taste aversion conditioning in male, Long-Evans rats. Doses of LiCl > or = 177 mumol/kg (or 7.5 mg/kg) induced significant, dose related taste aversions, but only doses of LiCl > or = 2123 mumol/kg (90 and 120 mg/kg) induced significant anorexia. CCK-8 induced marked anorexia (at doses > or = 25-50 nmol/kg), but only relatively mild taste aversions which were only statistically significant at the highest dose (1000 nmol/kg). The anorectic effects of CCK-8 at 500 and 1000 nmol/kg, but not at lower doses, lasted at least 3 hr. Sulfated CCK26-29, CCK30-33 and nonsulfated CCK-8 induced neither anorexia nor taste aversion. BOM induced marked anorexia at all doses tested, but did not induce statistically significant taste aversions. The nonpeptidal anorectic compounds, fenfluramine, fluoxetine, and AMPH, induced both dose-related anorexia and taste aversion conditioning. We focus on several issues concerning the interpretation of taste aversion conditioning. Our results challenge any simple relationship between the ability of a compound to induce taste aversion and to decrease feeding. PMID- 7791091 TI - Effects of cicletanine on kidney function. 2. Role of renal prostaglandins and kinins, and of muscarinic receptors. AB - We report the effect of the prostaglandin synthesis inhibitors indomethacin and meclofenamate, of the ACE-inhibitor captopril and of the muscarinic receptor antagonist methyl-scopolamine on the renal action of cicletanine (20-30 mg/kg i.v.) in anesthetized rats. Methylscopolamine, at doses ranging from 60 to 600 micrograms/kg i.v., did not at all affect cicletanine's action on the kidney's excretory function. Captopril (20 mg/kg i.v.) induced by its own a small rise of urine flow, and of urinary sodium and chloride excretion. The drug enhanced the effect of cicletanine on urine flow and sodium excretion by an additive effect. In the presence of captopril, and also of indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.), but not with control conditions, cicletanine significantly enhanced glomerular filtration rate and p-animohippurate clearance. Despite the fact that renal hemodynamics improved, the prostaglandin inhibitors nearly completely abolished cicletanine's effect on urinary fluid and electrolyte excretion. The results suggest that muscarinic receptors are not involved in the diuretic response to cicletanine. Cicletanine's diuretic and saluretic action may be related to a stimulation of renal prostaglandin synthesis. An enhanced prostaglandin production, and an activated reninangiotensin system, may also mask a direct vasodilating effect of cicletanine on the renal vasculature in the rat. PMID- 7791093 TI - Prenatal cocaine exposure selectively reduces mesocortical dopamine release. AB - The effect of prenatal exposure to cocaine on the release of [3H]dopamine and on presynaptic dopamine autoreceptor regulation of [3H]dopamine release in prelabeled frontal cortical, cingulate cortical and striatal slices was investigated. The release of [3H]dopamine that is evoked by high K+ was reduced by 20 to 28% in the cortical regions but not in striatum. This effect was observed at 10 days of age and persisted up to postnatal day 120 in rabbits that were exposed to cocaine during gestational days 8 to 29. Spontaneous [3H]dopamine release was increased by 18 to 22% in frontal and cingulate cortices but not in striatum of the 10- but not the 50- or 120-day-old rabbit that was exposed to cocaine during gestational days 8 to 29. Total [3H]dopamine accumulated in brain slices examined on postnatal days 10, 50 or 120 was not affected by prenatal cocaine exposure. Incubation of slices with dopamine dose-dependently inhibited K(+)-evoked [3H]dopamine release in both cortical and striatal slices. Prenatal cocaine exposure enhanced the responsiveness to in vitro dopamine in the two cortical regions but not in striatum. Fetal cocaine exposure did not affect the levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in frontal cortex or striatum. Similarly, no apparent differences in dopamine metabolism, as indicated by the ratio of 3,4 dihydroxyphenylacetic acid + homovanillic acid/dopamine, were observed in these brain areas. These findings demonstrate that prenatal cocaine exposure selectively affects depolarization-evoked [3H]dopamine release and its regulation by presynaptic dopamine autoreceptor in cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791094 TI - delta 9-Tetrahydrocannabinol modulates antigen processing by macrophages. AB - delta 9-Tetrahydrocannabinol (THC) exposure suppresses multiple immunological functions of macrophages. The ability of macrophages exposed to THC to process and present soluble protein antigens was investigated by the stimulation of antigen-specific helper T cell hybridomas to secrete interleukin-2. The T cell response to hen egg lysozyme was dramatically reduced after a 24-hr pretreatment of a macrophage hybridoma with THC. In contrast, THC exposure did not alter the capacity of the macrophage hybridoma to process chicken ovalbumin and augmented their presenting cell function for a pigeon cytochrome c response. These findings could not be attributed to differential effects of THC on either cell viability or expression of the antigen receptor-associated CD3 complex by the T cells. The level of T cell activation with peptides of lysozyme and cytochrome c, which do not require processing, was inhibited only at the highest concentrations of THC, suggesting that THC mainly affects antigen processing. Peritoneal macrophages exposed to THC during an antigen pulse and fixed with paraformaldehyde showed similar effects on the subsequent T cell responses to lysozyme and cytochrome c in the absence of THC, arguing against a possible influence of THC on the T cells. Therefore, THC differentially modulates the capacity of macrophages to process antigens that is necessary for the activation of CD4+ T cells. PMID- 7791095 TI - [3H]WIN 35,428 ([3H]CFT) binds to multiple charge-states of the solubilized dopamine transporter in primate striatum. AB - Caudate-putamen membranes of rhesus monkey were solubilized (1% digitonin; w/v) and [3H]WIN 35,428 ([3H]CFT: 2 beta-carbomethoxy-3- beta-(4-fluorophenyl)-N [3H]methyltropane) binding assayed. Saturation analysis revealed high- and low affinity binding components (KHIGH: 7.48 +/- 2.77 nM; KLOW: 292 +/- 788 nM; mean +/- SEM). Monoamine transport inhibitors and neurotransmitters had similar affinities for soluble and membrane [3H]CFT binding sites (r, 0.998; P < .001). The rank order of potency of these compounds for inhibiting [3H]CFT binding (Lu 19-005 > mazindol > CFT > GBR 12909 > (-)-cocaine > talsupram > dopamine > norepinephrine > citalopram) was consistent with [3H]CFT labeling cocaine binding sites on the dopamine transporter. [3H]CFT binding sites were separated into three protein fractions by anion-exchange chromatography. Monoamine transport inhibitors and neurotransmitters inhibited [3H]CFT binding in each fraction with a rank order of potency consistent with binding to the dopamine transporter. Detection of multiple binding components for [3H]CFT labeled sites by these drugs varied in each fraction. Size-exclusion chromatography indicated [3H]CFT bound to a single protein in each fraction (apparent molecular weight, 170 kDa). Therefore, multiple binding components for cocaine reside solely on the dopamine transporter and exhibit different affinities for drugs depending on the charge state of the transporter. PMID- 7791096 TI - Characterization of anandamide- and fluoroanandamide-induced antinociception and cross-tolerance to delta 9-THC after intrathecal administration to mice: blockade of delta 9-THC-induced antinociception. AB - The antinociceptive effects of the putative endogenous cannabinoid ligand anandamide (ANA) and its fluorinated analog, fluoroanandamide (FA), were determined as measured by the tail-flick and p-phenylquinone (PPQ) stretch tests. The ED50 values (confidence limits) for ANA and FA were 77 (52-13) and 7 (2-21) micrograms/mouse, respectively, for the tail-flick test and 30 (23-41) and 0.5 (0.1-2) micrograms/mouse, respectively, for the PPQ test after intrathecal (i.t.) administration. ANA was not significantly less potent than delta 9 tetrahydrocannabinol (THC) in the tail-flick test, but it was less potent in the PPQ test. FA was more potent than either ANA or THC in tail-flick test. The antinociceptive effects of all drugs (administered i.t.) were blocked significantly or nearly abolished by the pretreatment of the mice with pertussis toxin (i.t.). Pretreatment of the mice with 5 and 25 micrograms forskolin per mouse or 10 micrograms 8-(4-chlorophenyl-thio)-adenosine-3',5'-monophosphate cyclic monosodium salt per mouse (both i.t.) significantly attenuated the antinociception produced by THC but not by ANA or FA. Various calcium modulators were tested in combination with THC, ANA, and FA, but they failed to alter the antinociceptive effects of the drugs. Various potassium channel blockers were tested in combination with the drugs. Apamin, a blocker of small (low) conductance calcium-gated potassium channels that attenuates THC-induced antinociception, failed to alter ANA- or FA-induced antinociception. In contrast to THC, which is blocked by the kappa antagonist nor-binaltorphimine, ANA- and FA induced antinociception was not altered by classic opioid antagonists. Also in contrast to THC, which enhances mu and delta opioid-induced antinociceptive effects, ANA failed to significantly alter opioid antinociception. ANA significantly shifted the THC dose-effect curve to the right. Thus, ED50 for DMSO/THC in the tail-flick test was shifted from 14 (7-29) to 54 (38-77) micrograms/mouse and was shifted in the hot-plate test from 22 (12-42) to 63 (43 92) micrograms/mouse. The magnitude of the shift in the ED50 was 3.8-fold in the tail-flick test and 2.9-fold in the hot-plate test. The shifts were parallel and significant. The Ki for the displacement of 3H-CP 55,940 binding by ANA and FA was 214 nM (+/- 45 S.E.M.) and 72 nM (+/- 5 S.E.M.), respectively, in pure spinal cord synaptosomes from the rat. ANA and FA were significantly cross-tolerant to THC. Although similarities between ANA and cannabinoids were shown, several marked differences were observed between ANA and the classic cannabinoids. ANA appears to function as both a cannabimimetic and a blocker of cannabinoid-induced antinociception. PMID- 7791097 TI - Role of delta opioid receptors in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys. AB - The role of delta opioid receptors in the self-administration and discrimination of cocaine by rhesus monkeys was evaluated using the delta opioid antagonist naltrindole and the delta opioid agonist BW373U86 [(+/-)-4-((alpha R*)-alpha ((2S*,5R*)-4-Allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N diethylbenzamide dihydrochloride]. In the self-administration studies, monkeys were trained to respond for food (1 g banana pellets) or cocaine (0.032 mg/kg/injection, i.v.) under a second-order FR4(VR16:S) schedule of reinforcement during multiple daily food and drug sessions. Substitution of saline or other unit doses of cocaine (0.001-0.1 mg/kg/injection) for the maintenance dose of cocaine yielded typical inverted-U shaped dose-effect curves relating unit dose of cocaine to the number of saline or drug injections per day. The unit dose of cocaine available during drug sessions had little effect on food-maintained responding. In the drug discrimination studies, monkeys were trained to discriminate 0.4 mg/kg cocaine (i.m.) from saline in a two-lever, food-reinforced drug discrimination task. Cumulative dosing with cocaine (0.004-1.3 mg/kg) produced a dose-dependent generalization to the training dose of cocaine without consistently altering response rates. Initial experiments with naltrindole (0.1 3.2 mg/kg, i.v. or i.m.) produced effects in some monkeys suggesting that naltrindole may have antagonized the effects of cocaine under both procedures. In the drug self-administration studies, treatment with at least one dose of naltrindole for 10 consecutive days decreased self-administration of a unit dose of cocaine at the peak of the ascending limb of the cocaine dose-effect curve (0.01 mg/kg/injection) in three of four monkeys. In the drug discrimination studies, treatment with at least one dose of naltrindole shifted the cocaine dose effect curve 1/2 log unit to the right in two of four monkeys. However, naltrindole did not alter the effects of cocaine in all monkeys under either procedure. Furthermore, in the monkeys in which naltrindole was effective, the cocaine-antagonist actions of naltrindole were not replicable and were not monotonically related to dose. When the delta agonist BW373U86 (0.001-0.032 mg/kg/inj, i.v.) was substituted for cocaine in one monkey in which naltrindole decreased cocaine self-administration, BW373186 was not self-administered. In addition, BW373U86 (0.0032-0.32 mg/kg, i.m.) neither generalized to cocaine nor potentiated the effects of cocaine in the drug discrimination procedure. These results suggest that delta opioid receptors play, at best, a minor and inconsistent role in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys. PMID- 7791098 TI - Bradykinin receptor subtypes in rat lung: effect of interleukin-1 beta. AB - We have characterized bradykinin (BK) receptors in the rat lung and studied the effect of recombinant human interleukin-1 beta (IL-1 beta) on BK receptors in vitro and in vivo. In lung membranes, saturation studies with [3]BK revealed a single class of specific and saturable binding sites. The BK B1 antagonist des Arg9[Leu8]-BK was less effective in displacing [3H]BK binding sites from lung membranes. In contrast, the selective BK B2 antagonists, Hoe 140 (D-Arg [Hyp3,Thi5,D-Tic7,Oic8]-BK) and NPC 567 (D-Arg-[Hyp3,D-Phe7]-BK) fully inhibited the binding of [3H]BK to lung membranes with Ki values of 96.7 +/- 17.8 pM and 9.0 +/- 2.5 nM, respectively. Intratracheal administration of 500 U of IL-1 beta induced airway hyper-responsiveness to inhaled BK and neutrophilia in bronchoalveolar lavage fluid 18 to 24 hr later. Compared to naive or saline treated animals, IL-1 beta had no effect on [3H]BK binding characteristics at 4, 12 or 24 hr after IL-1 beta administration. Twenty-four hours after IL-1 beta instillation, there was no change in the affinity of the selective BK B1 or B2 antagonists when compared to control animals. In vivo, the selective BK B2 receptor antagonists, NPC 567 (3 mumol kg-1 i.v.) and Hoe 140 (100 nmol kg-1 i.v.), inhibited BK-induced increase in lung resistance, whereas the selective BK B1 antagonist, des-Arg9[Leu8]-BK (10 mumol kg-1 i.v.), was without effect. These data suggest that the action of BK in the rat lung is dependent mainly on the activation of the BK B2 receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791099 TI - Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking properties, in guinea pig cardiac isolated preparations. AB - The effects of N-(3,4-dimethoxyphenyl)-N-[3[[2-(3,4-dimethoxyphenyl) ethyl] propyl]-4-nitrobenzamide hydrochloride (BRL-32872), a novel antiarrhythmic agent, were studied in guinea pig cardiac preparations using standard microelectrode and patch-clamp techniques. In papillary muscle, BRL-32872 did not change resting membrane potential and maximum rate of depolarization but prolonged action potential duration (APD) by 24% +/- 2% at 1.0 microM. When the concentration was increased to 3.0 and 10.0 microM, the effect on APD was not further enhanced, and a bell-shaped dose-response curve resulted. Patch-clamp experiments in isolated myocytes showed that BRL-32872 inhibited the rapidly activating component of the delayed rectifier potassium current (EC50 = 0.028 microM) and the L-type calcium current (EC50 = 2.8 microM) but had a limited effect on the inward rectifier potassium current. In papillary muscles stimulated at 300, 500, 1000 and 2000 msec, the effect of BRL-32872 in prolonging APD did not vary (P = .717). By contrast, N-(4-(1-[2-(6-methyl-2-pyridyl)ethyl]-4-piperidyl)- carbonyl]phenyl)methanesulfonamide dihydrochloride dihydrate (E-4031), a pure class III antiarrhythmic agent, increased APD more at slower than at faster stimulation rates (P = .001), which illustrated the reverse frequency-dependence of this agent. Among the 35 experiments performed with BRL-32872, only one fiber showed early afterdepolarizations (EADs), and these, which occurred at 1.0 microM, were suppressed at higher concentration (3.0 microM). Moreover, EADs induced by E-4031 were suppressed by BRL-32872 (3.0 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791100 TI - Does [3H]2-methoxy-idazoxan (RX 821002) detect more alpha-2-adrenoceptor agonist high-affinity sites than [3H]rauwolscine? A comparison of nine tissues and cell lines. AB - The authors compared [3H]2-methoxy-idazoxan (RX 821002) and [3H]rauwolscine binding in rat cerebral cortex, spleen and kidney; guinea pig kidney; porcine kidney; human kidney and platelets and HEL and NG 108-15 cells. [3H]RX 821002 had less nonspecific binding and higher affinity than [3H]rauwolscine in most models. Although both ligands detected similar alpha-2 adrenoceptor numbers in rat, porcine and human kidney and in NG 108-15 cells in saturation experiments, [3H]RX 821002 detected more alpha-2 adrenoceptors than [3H]rauwolscine in rat cerebral cortex and spleen, guinea pig kidney, human platelets and HEL cells. These differences were seen in Tris and in glycylglycine buffer regardless of whether EDTA, MgCl2, MgCl2 plus GTP or GTP plus NaCl was added to the former and were not explained by additional labeling of serotonin or dopamine receptors or nonadrenergic sites; in contrast, [3H]rauwolscine also labeled nonadrenergic sites in porcine kidney. In prazosin competition experiments, both ligands differentially recognized alpha-2-adrenoceptor subtypes but this could not account for the observed differences in detected receptor numbers. In epinephrine competition experiments, both ligands labeled similar numbers of agonist low affinity sites in all models; [3H]RX 821002, however, labeled more agonist high affinity sites than [3H]rauwolscine did in models in which it detected a greater total number of receptors. It was concluded that [3H]RX 821002 is a more suitable ligand for the detection of alpha-2 adrenoceptor than [3H]rauwolscine because of less nonspecific binding, higher affinity and greater specificity for alpha-2 adrenoceptors; moreover, [3H]rauwolscine appears not to detect all agonist high affinity sites of alpha-2 adrenoceptors. PMID- 7791101 TI - Disposition of the bromosulfophthalein-glutathione conjugate in the isolated perfused rat kidney. AB - Renal elimination of the bromosulfophthalein-glutathione conjugate (BSP-GSH) after its i.v. administration in the rat in vivo is negligible. In our study we wanted to establish whether the high albumin-binding of BSP-GSH constitutes the major restrictive factor toward the urinary excretion of the compound. The renal disposition of BSP-GSH was studied in the isolated rat kidney during perfusions with or without albumin in the perfusate. The urinary clearance of BSP-GSH in the absence of albumin was very low (< 60 microliters/min) as compared to the inulin clearance (approximately 300 microliters/min). This indicates that albumin binding is not the major reason for the low urinary clearance of BSP-GSH. Addition of albumin to the perfusate further decreased the urinary excretion by 60%. BSP-GSH is metabolized by the kidney into two major metabolites: the cysteinylglycine conjugate and the di-glutathione conjugate. Both metabolites appear in perfusate, which suggests that BSP-GSH undergoes tubular (re-)uptake. The di-glutathione conjugate is further metabolized to the di-cysteinylglycine conjugate. The di-glutathione conjugate and the di-cysteinylglycine conjugate are the major urinary components and the urinary elimination of BSP-GSH may depend on their formation. Inhibition of gamma-glutamyl transpeptidase activity with acivicin largely prevented the degradation to the cysteinylglycine and dicysteinylglycine conjugates of BSP. The total rate of urinary excretion, however, was only slightly lowered by acivicin. Apparently, cleavage of the gamma glutamyl moiety is not relevant for the total urinary elimination of BSP-GSH. PMID- 7791102 TI - Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine induced cognition deficit in monkeys. AB - Imidazenil is a highly potent partial allosteric modulator of gamma-aminobutyric acid action at a great variety of gamma-aminobutyric acid(A) receptors, whereas alprazolam is a full allosteric modulator at these receptors. Data in rats indicate that imidazenil, like alprazolam, has pharmacological effects in animals indicative of anxiolytic, antipanic and anticonvulsant activity in humans, but unlike alprazolam, in animals imidazenil does not produce ataxia, sedation, tolerance or dependence nor does it potentiate the effects of ethanol. To extend the study of the imidazenil pharmacological profile, we administered this drug and alprazolam, alone and in combination, in monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance), the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.01-0.32 mg/kg, p.o.) was administered alone, the overall response rate in both learning and performance decreased and the percent errors in both components increased with increasing doses. Learning, however, was more sensitive than performance; i.e., error-increasing effects were seen in learning at doses that had no effect on performance accuracy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791104 TI - The effect of carbidopa and entacapone pretreatment on the L-dopa pharmacokinetics and metabolism in blood plasma and skeletal muscle in beagle dog: an in vivo microdialysis study. AB - The effects of carbidopa and entacapone pretreatment on the pharmacokinetics and metabolism of i.v. administered L-3,4-dihydroxyphenylalanine (L-dopa) have been examined in vivo in blood plasma and skeletal muscle extracellular fluid (ECF), in beagle dog, by microdialysis. Both with or without carbidopa, blood plasma L dopa levels declined biexponentially after the i.v. administration of L-dopa. In contrast to blood plasma, a monoexponential decline was observed in muscle ECF in both these pharmacological conditions. Pretreatment with carbidopa had no significant effect on the pharmacokinetic parameters of L-dopa in blood plasma, but resulted in an increase in the area under the concentration versus time curve (AUC) and elimination half-life (t1/2) of L-dopa in muscle ECF (0.61 hr), compared with values achieved after L-dopa alone. Carbidopa pretreatment enhanced the accumulation of 3-O-methyldopa (3-OMD) and dopamine (DA) in muscle ECF but decreased that of L-3,4-dihydroxyphenylacetic acid (DOPAC) in both blood plasma and muscle ECF. Entacapone had a pronounced inhibitory effect on the formation of 3-OMD, resulting in a reduction of the AUC for 3-OMD by 98% and 85% in blood plasma and muscle ECF, respectively. Pretreatment with carbidopa plus entacapone enhanced the Tmax of L-dopa in muscle ECF compared with the values achieved after pretreatment with carbidopa alone. In addition, the elimination half-life (2.66 hr) and volume of distribution by area of L-dopa in blood plasma and its AUC and t1/2 in muscle ECF (1.80 hr) were enhanced substantially. No DA was detected, but DOPAC levels were enhanced in both blood plasma and muscle ECF. These results suggested that carbidopa has a L-dopa-sparing effect in skeletal muscle, which is further enhanced by entacapone. PMID- 7791103 TI - Regulation of ion transport by endothelins in rat colonic mucosa: effects of an ETA antagonist (FR139317) and an ETB agonist (IRL1620). AB - Rat colonic mucosa contains ETA and ETB receptors with Kd values for endothelin (ET)-1 of 32 and 11 pM and maximal binding capacities of 277 and 181 fmol/mg protein, respectively. In muscle-stripped rat colon without tonic nerve activity in Ussing chambers, the serosal addition of ET-1, ET-3 and IRL1620 inhibited amiloride-sensitive noncoupled Na+ entry and enhanced diphenylamine-2-carboxylate sensitive Cl- secretion, producing a sustained decrease and a transient increase in the short-circuit current (Isc) and the transepithelial conductance, respectively. EC50 values of ET-1, ET-3 and IRL1620 and the maximal changes in Isc were 2.0, 10.2 and 10.9 nM and -12.7, -7.0 and -7.1 muA/cm2, respectively for the Na+ entry; these values were 50, 220 and 225 nM and +57.3, +47.3 and +21.3 muA/cm2, respectively, for the Cl- secretion. FR139317 (100 nM) inhibited ET-1 induced Na+ and Cl- movements, shifting the concentration-response curves to the right (EC50 = 25 nM and 1 microM, respectively), and inhibited ET-3 (> 100 nM) induced Cl- movement, decreasing the maximal response to 35%, but it did not inhibit either ET-3-induced Na+ movement nor IRL1620-induced Na+ and Cl- movements. The removal of serosal Ca++ reduced 100 nM ET-1- and IRL1620-evoked changes in Isc by 50% and 70% for the Na+ entry and by 80% and 100% for the Cl- secretion, respectively. Indomethacin (1 microM) also reduced changes in Isc by 30% and 70% for the Cl- secretion but did not affect the Na+ entry. Our results show that ETA and ETB receptors regulate Na+ and Cl- transport by different mechanisms. PMID- 7791105 TI - Right heart failure impairs hepatic oxygenation and theophylline clearance in rats. AB - The effect of right heart failure on theophylline clearance was investigated in rats in which right ventricular pressure overload was produced by pulmonary artery constriction (PAC). Fifteen wk after the surgery, compared to sham operated controls (n = 9), PAC rats (n = 9) showed markedly elevated mean central venous pressure (11 +/- 3 vs 1.44 +/- 0.88 mm Hg, P = .0001), and increased right ventricular weight (0.229 +/- 0.047 vs 0.124 +/- 0.013 g/100 g body weight, P = .0001). Centrilobular hepatic congestion was present in all PAC rats and total hepatic oxygen delivery was reduced significantly compared to controls (146 +/- 58 mumols/min vs. 206 +/- 28 mumol/min; P = .025). In the PAC group, theophylline clearance was reduced (0.82 +/- 0.12 ml/min vs. 0.96 +/- 0.13 ml/min in controls; P = .014), and there was a nonlinear correlation between theophylline clearance and total hepatic oxygen delivery (r = .82). These results suggest that in animals with PAC, metabolism of theophylline was impaired as a result of a reduction in total hepatic oxygen delivery. Therefore, in addition to the known effect of reduced hepatic blood flow on the hepatic clearance of "flow limited" drugs, reduction of hepatic oxygen delivery may be another important mechanism that can lead to reduction in hepatic clearance of capacity-limited drugs in congestive heart failure. PMID- 7791106 TI - Effects of beta adrenoceptor agonists and antagonists on adrenal catecholamine release in response to splanchnic nerve stimulation in anesthetized dogs: role of beta-1 and beta-2 adrenoceptors. AB - The present study was performed to examine whether beta adrenoceptor agonists and antagonists modify the release of adrenal catecholamine (CA) in response to splanchnic nerve stimulation (SNS) in anesthetized dogs, in order to elucidate the beta adrenoceptor-mediated modulation of adrenal CA release. SNS at 3 Hz produced marked increases in both epinephrine and norepinephrine output determined from adrenal venous blood. Atenolol (10, 30 and 100 micrograms/kg, i.v.) and CGP20712A (10 and 30 micrograms/kg, i.v.), selective beta-1 adrenoceptor antagonists, significantly enhanced the SNS-induced increases in CA output. Neither ICI118551 (10, 30 and 100 micrograms/kg, i.v.), a selective beta 2 adrenoceptor antagonist, nor nadolol (10, 30 and 100 micrograms/kg, i.v.), a nonselective beta adrenoceptor antagonist, affected the SNS-induced increases in CA output. After the treatment with ICI118551 (100 micrograms/kg, i.v.), atenolol (10, 30 and 100 micrograms/kg, i.v.) failed to enhance the SNS-induced increases in CA output. On the other hand, neither isoproterenol (0.03 and 0.1 micrograms/kg/min, i.v.) nor the selective beta-2 adrenoceptor agonist procaterol (0.03 and 0.1 micrograms/kg/min, i.v.) affected the SNS-induced increases in CA output. After the treatment with atenolol (100 micrograms/kg, i.v.), both isoproterenol (0.03 micrograms/kg/min, i.v.) and procaterol (0.03 micrograms/kg/min, i.v.) enhanced the SNS-induced increases in CA output. The enhancing effects of isoproterenol and procaterol were abolished by ICI118551 (100 micrograms/kg, i.v.). These results indicate that activation of beta-2 adrenoceptors facilitates the SNS-evoked release of CA from the dog adrenal medulla under the condition in which beta-1 adrenoceptors are blocked, and they suggest that activation of beta-1 adrenoceptors inhibits the beta-2 adrenoceptor mediated facilitation process of adrenal CA release. PMID- 7791107 TI - Buprenorphine antagonism of mu opioids in the rhesus monkey tail-withdrawal procedure. AB - The apparent in vivo dissociation constant (KA) and relative efficacy values for alfentanil, etonitazene, morphine, and nalbuphine were determined by comparing the effects of these agonists in the presence of buprenorphine with the effects of these agonists alone in the rhesus monkey tail-withdrawal procedure. Initial time course studies of buprenorphine alone indicated that 3.2 and 10 mg/kg produced increases in tail-withdrawal latencies when studied with 48 degrees C water for 48 hr. No increases in tail-withdrawal latency were found with either dose studied with 55 degrees C water. Buprenorphine produced dose-dependent shifts to the right for the antinociceptive effects of alfentanil, etonitazene, morphine and nalbuphine 72 hr after administration and decreased the maximal effects of morphine in 48 degrees C water and those of alfentanil and etonitazene in 55 degrees C water. Buprenorphine administration decreased the receptors available for agonist interaction to approximately 2%. The average apparent in vivo dissociation constant (KA) values for alfentanil, etonitazene, morphine and nalbuphine were 3.3, 0.073, 60 and 31 mg/kg, respectively. High efficacy estimates were determined for alfentanil (149-203) and etonitazene (174-203), whereas lower efficacy estimates were determined for nalbuphine (57) and morphine (17). The apparent in vivo dissociation constant of a pseudoirreversible antagonist (KB) value for buprenorphine averaged 0.15 mg/kg across agonists, temperatures and buprenorphine doses. These data extend and emphasize the significance of in vivo estimates of affinity and relative efficacy for drug classification. PMID- 7791108 TI - Increased sensitivity to mu opiate antinociception in the neonatal rat despite weaker receptor-guanyl nucleotide binding protein coupling. AB - The developmental changes in mu opiate receptor-mediated antinociception and coupling to guanyl nucleotide binding proteins were studied in the rat. ED50 values for morphine- and sufentanil-induced antinociception were determined in the paw-lift assay on days 10 and 27. The ED50 for morphine analgesia in 10-day old pups was 0.35 mg/kg and increased with age to 5.3 mg/kg on day 27. Similarly, sufentanil was more potent in pups than in weanlings, the ED50 increasing from 1.7 to 7.6 micrograms/kg. Serum and brain morphine levels after 5 mg/kg of morphine were higher in neonates (day 10) than weanlings (day 27), largely due to a more rapid redistribution phase in weanlings (T1/2 = 26 min.) than in pups (T1/2 = 2.5 hr). Additionally, a substantial (70%) antinociceptive response was achieved in neonates at brain morphine levels that were one-half those producing an equal effect in weanlings. Radioligand binding studies indicated that the number of mu receptors increased 2-fold without change in affinity between days 10 and 27, whereas the GTP analog guanylylimidophosphate was nearly twice as effective in shifting the mu receptors from high to low affinity on day 27 than on day 10. These data indicate that neonatal rats are more sensitive to mu opiate antinociception despite apparently weaker receptor-guanyl nucleotide binding protein coupling. This greater sensitivity is enhanced by the pharmacokinetic differences between neonates and weanlings which result in higher drug levels in pups after a similar dose. PMID- 7791109 TI - The ontogeny of mu opiate tolerance and dependence in the rat: antinociceptive and biochemical studies. AB - The ontogeny of tolerance to mu opiate antinociception and the behavioral and endocrine profiles of the opiate withdrawal syndrome were studied in rats. Animals were treated with saline or an increasing dose regimen of morphine for 5 days (5-25 mg/kg b.i.d. s.c.) and were tested 36 hr later for morphine or sufentanil antinociception in the hot-plate paw-lift test, or withdrawal was precipitated with 5 mg/kg of naloxone 12 hr after the last chronic morphine dose. Twenty-seven-, 20- and 15-day-old rats all developed tolerance as indicated by a rightward shift of the dose-response curve after chronic morphine. Animals treated on days 4 to 8 and tested on day 10 did not develop tolerance to the same chronic dose regimen used in older animals. In contrast to the observed developmental difference in tolerance, both neonatal and weanling rats developed physical dependence after morphine treatment, as evidenced by the presence of withdrawal symptoms after naloxone administration. Withdrawal in weanling rats was characterized by ptosis, piloerection, abnormal posture, forepaw treading, vocalization on touch and mastication. In addition, both serum corticosterone and adrenocorticotropic hormone secretion were increased during passive withdrawal. The behaviors constituting the withdrawal syndrome precipitated in neonates were distinct from those in weanling rats. Spontaneous vocalization, wall climbing, tremor, mouthing and increased locomotion were all observed. As in the older animals, both serum corticosterone and adrenocorticotropic hormone secretion were elevated during passive withdrawal. Tremor also was induced in opiate naive neonates when naloxone (5 mg/kg) was administered 2 hr after a single 25-mg/kg morphine injection. Brain and serum morphine levels and the time course of antinociception were not altered by chronic morphine treatment at any age. Saturation binding assays in brain homogenates indicated that chronic morphine did not produce changes in receptor number or affinity for the antagonist. The shift induced by the guanine nucleotide Gpp(NH)p (10 microM) from high to low affinity on days 27 and 10, respectively, was not altered by chronic morphine treatment. These data indicate that 10-day-old rats are refractory to developing tolerance relative to older animals, and that changes in receptor number or coupling to guanine nucleotide proteins do not accompany tolerance to this regimen. PMID- 7791110 TI - Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats. AB - Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4 morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle. PMID- 7791112 TI - Characterization of the facilitatory prejunctional purinoceptor on adrenergic nerves of the rabbit ear artery. AB - The effects of a number of purinoceptor agonists and antagonists on the release of endogenous norepinephrine (NE) from electrically field-stimulated (2 ms, 4 Hz) rabbit ear arteries were determined. NE was quantified by high-performance liquid chromatography and electrochemical detection techniques. Both P1- and P2 purinoceptor agonists enhanced the release of NE in a concentration-dependent manner (0.1 microM-100 microM), the relative order of potency being beta, gamma methylene ATP (beta gamma-mATP) > 2-chloroadenosine (2CA) > ATP > L phenylisopropyl-adenosine > 2-methylthio ATP > 5'N-ethylcarboxamido-adenosine. Adenosine and alpha, beta-methylene ATP (alpha beta-mATP) at 100 microM did not significantly enhance the electrical field stimulation-evoked release of NE. None of drugs changed the spontaneous overflow of NE. Pretreatment with alpha beta mATP (1, 10 microM), a P2x-purinoceptor desensitizing agent, and 8-sulfophenyl theophylline (8SPT; 1 and 10 microM), a P1-purinoceptor antagonist, caused a shift to right of the concentration-release curve for beta gamma-mATP. alpha beta mATP and 8SPT did not by themselves significantly affect the spontaneous overflow and the electrical field stimulation-evoked release of NE. Pretreatment of alpha beta-mATP (30 microM) and 8SPT (30 microM) antagonized facilitation of NE release by 2CA (10 microM). The concentration-contraction curve for beta gamma-mATP (1 300 microM) in the rabbit ear artery was shifted to the right by alpha beta-mATP (30 microM) but not by 8SPT (30 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791111 TI - Effects of a novel KATP channel blocker on renal tubule function and K channel activity. AB - ATP-sensitive potassium channels (KATP) modulate Na, K and Cl reabsorption in the thick ascending limb of the loop of Henle and K secretion in the cortical collecting tubule. Inhibition of potassium recycling in the apical membrane of the thick ascending limb of the loop of Henle interferes with sodium reabsorption and suppression of the apical potassium conductance in principal cells of the cortical collecting tubule and reduces potassium secretion. Both potassium recycling and potassium secretion depend critically on the activity of KATP, and recent studies indicate that the sulfonylurea compound glyburide, a known KATP channel blocker, is diuretic but does not produce kaliuresis. PMID- 7791113 TI - Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: correlation between function and interaction with a high affinity rolipram binding site. AB - In this report, we describe the ability of selective inhibitors of phosphodiesterase (PDE) isozymes to increase aminopyrine accumulation in rabbit isolated gastric glands. Aminopyrine accumulation in the presence of histamine was increased by the nonselective PDE inhibitor isobutylmethylxanthine (EC50 = 4.8 microM) and by two selective PDE IV inhibitors, rolipram and Ro 20-1724 (EC50 = 0.013 and 0.07 microM, respectively) but not by selective PDE III inhibitors (siguazodan and SK&F 94120) or by a selective PDE V inhibitor (zaprinast). These results suggest that PDE IV is an important regulator of acid secretion in response to histamine. One of the more fascinating properties of PDE IV is the expression of a high-affinity binding site for [3H]-rolipram in addition to cAMP catalytic activity. Although agents that inhibit PDE IV catalytic activity also appear to bind to the high-affinity rolipram-binding site, the rank-order potencies of compounds for these two effects are poorly correlated. Also, certain pharmacological actions of PDE IV inhibitors appear to be related to an interaction with this binding site. In this study, we observed that the ability of PDE IV inhibitors to enhance acid secretion was not associated with their ability to inhibit PDE IV catalytic activity but did show a strong correlation with their ability to compete for [3H]-rolipram binding. Furthermore, we were able to detect [3H]-rolipram binding sites in gastric glands that had characteristics similar to those of the [3H]-rolipram binding sites in rat brain microsomes and human recombinant PDE IV. PMID- 7791114 TI - A possible involvement of sodium channel blockade of class-I-type antiarrhythmic agents in postischemic contractile recovery of isolated, perfused hearts. AB - The present study was undertaken to test the hypothesis that the degree of sodium channel blockade by class-I-type antiarrhythmic agents accounts for enhancement of postischemic contractile recovery of ischemic/reperfused hearts. Electrophysiological studies showed that the class-I-type antiarrhythmic agents quinidine, disopyramide, procainamide, lidocaine, mexiletine, flecainide and pilsicainide suppressed the Vmax value of the rat left ventricular muscle cell, a marker of sodium channel blockade, in a concentration-dependent manner. Isolated rat hearts were subjected to 35 min of ischemia and 60 min of reperfusion. Postischemic contractile recovery, which was never detected in untreated hearts, was enhanced in hearts pretreated with these antiarrhythmic agents during the last 3 min before ischemia at concentrations ranging from 3 to 300 microM. Tissue Na, but not Ca, accumulation was also detected in the ischemic heart, and tissue Na and Ca accumulation was observed in the reperfused heart, which suggests that sodium overload occurs during ischemia, followed by sodium and calcium overload during reperfusion. The degree of postischemic contractile recovery seen in the presence of these antiarrhythmic agents was inversely related to tissue Na or Ca accumulation after reperfusion, which suggests that class-I-type antiarrhythmic agents inhibit sodium overload occurring in ischemic/reperfused myocardial cells. A close relationship between postischemic contractile recovery of the perfused heart and depression in the Vmax value of the ventricular muscle was also observed. These results suggest that the ability class-I-type antiarrhythmic agents to inhibit myocardial sodium channels plays a significant role in the enhancement of postischemic contractile recovery of the ischemic/reperfused heart. PMID- 7791115 TI - Pharmacological characterization of PD 156707, an orally active ETA receptor antagonist. AB - We describe the pharmacological characteristics of PD 156707 (sodium 2 benzo[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5- trimethoxy-benzyl)-but 2-enoate), a potent, orally active, nonpeptide antagonist of the endothelin A (ETA) receptor subtype. PD 156707 was designed on the basis of a compound identified by screening the Parke-Davis chemical library. PD 156707 is highly selective for the ETA receptor (ETAR) and inhibits the binding of [125I]-ET-1 to cloned human ETAR and ETBR with Ki values of 0.17 and 133.8 nM, respectively. PD 156707 antagonizes ET-1-stimulated phosphoinositide hydrolysis in Ltk- cells expressing cloned human ETAR with an IC50 value of 2.4 nM. PD 156707 inhibits vasoconstriction in isolated blood vessels mediated by ETAR (rabbit femoral artery) and ETBR (rabbit pulmonary artery) with pA2 values of 7.5 and 4.7, respectively. PD 156707 administered orally to rats blocked subsequent ETAR mediated pressor responses in vivo but had no effect on ETBR-mediated dilator responses. As a potent and orally active ETA-selective antagonist, PD 156707 will be useful in defining the physiological and pathological roles of ETAR. PMID- 7791116 TI - Antagonist properties of LY 165,163 at pre- and postsynaptic dopamine D2, D3 and D1 receptors: modulation of agonist actions at 5-HT1A receptors in vivo. AB - In this study, we examined the influence of the actions of the halogenated phenylpiperazine LY 165,163 at dopamine D1, D2 and D3 receptors on its 5-HT1A agonist properties in vivo. LY 165,163 displayed marked affinity at striatal rat (r)D2 (pKi = 7.0), cloned rD2 (pKi = 7.3), cloned rD3 (pKi = 8.0), cloned human (h)D2 (pKi = 7.2) and cloned hD3 (pKi = 7.8) receptors, whereas its affinity at striatal rD1 receptors was weak (pKi = 5.7). In contrast, the prototypical 5-HT1A agonist 8-OH-DPAT displayed low affinity at each of these sites (pKi < 5.5). In vivo, LY 165,163 behaved as an antagonist at D2 autoreceptors in enhancing the synthesis of dopamine throughout the brain. Consistently with antagonist properties at postsynaptic D2 receptors, in unilateral substantia nigra-lesioned rats, the rotation elicited by the D2 agonist quinpirole was potently blocked by LY 165,163, whereas that elicited by the D1 agonist SKF 38393 was only weakly inhibited. In addition, LY 165,163 potently evoked prolactin secretion in rats and abolished apomorphine-induced climbing in mice. At native rat 5-HT1A receptors and cloned human 5-HT1A receptors, LY 165,163 (pKi values of 8.7 and 8.9, respectively) mimicked the high affinity of 8-OH-DPAT (pKi values of 9.0 and 9.2). Further, like 8-OH-DPAT, LY 165,163 acted as an agonist in inhibiting the firing of dorsal raphe nucleus neurons, in reducing striatal turnover of 5-HT and in eliciting both hypothermia and corticosterone secretion. However, in contrast to 8-OH-DPAT, LY 165,163 failed to evoke spontaneous tail-flicks (STFs). This difference probably reflects its D2 antagonist properties because the induction of STFs by 8-OH-DPAT was, in contrast to its induction of hypothermia and corticosterone secretion, blocked by the preferential D2 antagonist haloperidol. Moreover, in the presence of quinpirole and in the presence of a further dopaminergic agonist, apomorphine, LY 165,163 did elicit STFs. Further, STFs evoked by LY 165,163 in the presence of apomorphine were abolished by the 5-HT1A antagonists (-)-alprenolol, BMY 7378 and NAN-190. We conclude that LY 165,163 exhibits marked activity at both pre- and postsynaptic dopaminergic D2 (D3 and D1) receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7791117 TI - mu-, delta- and kappa-opiate receptors mediate antinociception in the rat tail flick test following noxious thermal stimulation of one hindpaw. AB - Experiments were performed to investigate the possible involvement of spinal mu-, delta- and kappa-opiate receptors in mediating the antinociceptive effects of noxious thermal stimulation of one hindpaw on the tail flick reflex in the rat. Male Sprague-Dawley rats were implanted with chronic intrathecal catheters to the lumbar level of the spinal cord. After 5 to 7 days, they were lightly anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). After baseline readings were taken in the tail flick test a conditioning noxious thermal stimulus, which consisted of immersion of one hindpaw in water at 55 degrees C for 90 sec, was applied and the effects on the latency of the tail withdrawal reflex were studied over the next 30 min. In animals pretreated with CSF intrathecally 10 min before the stimulus, an increase in tail flick reaction time was observed peaking at 30 sec after the stimulus. This response was attenuated in a dose-related manner by preadministration of the specific mu-opiate receptor antagonist, beta funaltrexamine, the specific delta-opiate receptor antagonist, H-Tyr-Tic psi[CH2NH]-Phe-Phe-OH or the specific kappa-opiate receptor antagonist, nor binaltorphimine. The data show that the antinociceptive effect on the tail withdrawal reflex from a brief noxious thermal stimulus is provoked heterosegmentally by the noxious conditioning stimulus to the hindpaw and is mediated by the endogenous release of ligands that bind to mu-, delta- and kappa opiate receptors in the spinal cord. PMID- 7791118 TI - Characterization of [3H]ABT-418: a novel cholinergic channel ligand. AB - ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole] is a potent and selective agonist at neuronal nicotinic acetylcholine receptors (nAChRs) with cognitive enhancing and anxiolytic activities. [3H]ABT-418 was found to bind with high affinity (KD = 2.85 +/- 0.14 nM) to membranes prepared from rat brain. Binding of [3H]ABT-418 was characterized by rapid association (T1/2 = 1.4 +/- 0.3 min) and dissociation (T1/2 = 2.9 +/- 0.4 min) half-times. The pharmacology of [3H]ABT-418 binding was consistent with an interaction with the putative alpha 4 beta 2 nAChR subtype. The nAChR agonists, (-)-nicotine, (-)-cytisine and (+/-) epibatidine, displayed a high affinity (Ki = 0.8 +/- 0.1, 0.2 +/- 0.1 and 0.05 +/ 0.01 nM, respectively) for [3H]ABT-418 binding sites, whereas among nAChR antagonists examined, only dihydro-beta-erythroidine competed with high affinity (Ki = 32 +/- 1.5 nM). Although autoradiography studies indicate that the binding distribution of [3H]ABT-418 and (-)-[3H]cytisine are largely identical, there are some brain regions including the striatum, olivary pretectal nucleus and the superior colliculus, in which [3H]ABT-418 demonstrates significantly (P < .05) less binding. The data in the present study demonstrate that [3H]ABT-418 binds with high affinity to a population of binding sites in the rat brain that have the pharmacological characteristics of neuronal nAChRs. [3H]ABT-418 may, therefore, serve as a useful radioligand to further probe the observed differences in pharmacological properties between ABT-418 and other nicotinic agonists in vivo. PMID- 7791119 TI - Carvedilol, a new vasodilating beta-adrenoceptor blocker, inhibits oxidation of low-density lipoproteins by vascular smooth muscle cells and prevents leukocyte adhesion to smooth muscle cells. AB - The present study was undertaken to assess the effect of carvedilol, a new vasodilating beta-adrenoceptor blocker with antioxidant activity, on the oxidation of low-density lipoproteins (LDL) by rat aortic smooth muscle cells (RASMC). LDL oxidation was assessed as thiobarbituric acid reactive substances (TBARS) formation and increase in electrophoretic mobility. Oxidized (ox) LDL induced cytotoxicity was assessed as lactate dehydrogenase release (LDH) from cells and ox-LDL-enhanced adhesiveness of the RASMC for leukocytes was also determined. Carvedilol inhibited TBARS formation and LDH release from RASMC with IC50 values of 1.74 and 1.62 microM, respectively. Under the same conditions, the IC50 values of probucol and nicardipine were 2.33 and 5.60 microM, respectively, for inhibition of TBARS and 5.16 and 12.10 microM, respectively, for inhibition of LDH release; propranolol, atenolol, pindolol and labetalol, at concentrations up to 100 microM, had virtually no effect on either variable. RASMC-dependent ox LDL stimulated the adhesive properties of RASMC for both monocytes and neutrophils in a concentration- and time-dependent manner, which were prevented when the RASMC were treated with carvedilol (IC50 2.07 microM for monocytes and 1.12 microM for neutrophils), whereas other beta blockers, at concentrations up to 30 microM, had only mild effects. The monoclonal antirat intercellular adhesion molecule-1 antibody partially inhibited ox-LDL-induced adhesion of RASMC for monocytes and neutrophils. Northern analysis demonstrated that ox-LDL induced intracellular adhesion molecule-1 messenger RNA expression on RASMC, which was inhibited by carvedilol and probucol via inhibition of LDL oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791121 TI - Ontogenically related properties of N-methyl-D-aspartate receptors in rat hippocampal neurons and the age-specific sensitivity of developing neurons to lead. AB - The sensitivity of N-methyl-D-aspartate- (NMDA) induced whole-cell and single channel currents to Pb2+ was studied in neurons acutely dissociated from the hippocampus of 3- to 30-day-old rats. The amplitude of NMDA-induced whole-cell currents in the neurons increased with age of the animals until they were 10 to 12 days old, thereafter remaining nearly unchanged. As in cultured hippocampal neurons, Pb2+ at both 10 and 30 microM inhibited NMDA-induced currents, and the sensitivity of the currents to Pb2+ decreased with age of the rats. The sensitivity correlated with the age-related expression of two components of the NMDA-induced currents, one that was fast decaying and more prominent in younger neurons, and the other slowly decaying. Inhibition of the fast component by Pb2+ was always greater than that of the slow component, which may explain the greater sensitivity of younger neurones to Pb2+. may explain the greater sensitivity of younger neurons to Pb2+. The use of trypsin during acute dissociation of the neurons did not qualitatively alter the findings, although in the trypsin-treated neurons the currents were 65% smaller, and the EC50 for NMDA and glycine for the slow component were both about two times greater than in the untreated neurons; in the case of the fast component, the EC50s for NMDA and for glycine were not significantly altered. In outside-out patches excised from acutely dissociated hippocampal neurons, Pb2+ decreased the frequency of NMDA-activated channel openings without altering the mean channel open time. Our results are in agreement with those reported for embryonic neurons that developed in culture, and indicate that NMDA receptors expressed in hippocampal neurons of young animals are key target sites for the neurotoxic actions of Pb2+. PMID- 7791122 TI - Nicotinic responses in acutely dissociated rat hippocampal neurons and the selective blockade of fast-desensitizing nicotinic currents by lead. AB - The patch-clamp technique was used to characterize the nicotinic currents in individual neurons acutely dissociated from the hippocampi of postnatal rats of different ages, and to investigate the effects of Pb2+ on these currents, both in acutely dissociated and in cultured hippocampal neurons. The effects of Pb2+ on nicotinic acetylcholine receptors (nAChR) expressed in frog muscle fibers were also investigated. Acetylcholine could activate fast- and slowly desensitizing whole-cell currents in neurons dissociated from the hippocampi of 4- to 20-day old rats. Similar to the currents elicited in cultured hippocampal neurons, the rapidly desensitizing currents were blocked by methyllycaconitine, and were the nicotinic responses that could be elicited in most of the acutely dissociated neurons tested, whereas the slowly desensitizing currents could be evoked only in a few neurons. Although the peak amplitude of nicotinic currents recorded from acutely dissociated neurons increased with age of the neurons as it did in cultured neurons, the mean amplitude of the currents was at least an order of magnitude smaller in acutely dissociated neurons than in cultured neurons. Pb2+ could potently and specifically inhibit activation of fast-desensitizing nicotinic currents in hippocampal neurons. Pb2+ reduced the peak amplitude of fast-desensitizing currents with an IC50 of about 3 microM and an apparent Hill coefficient of 1.0, whereas only at 30 microM could Pb2+ decrease the peak amplitude of slowly desensitizing currents by about 50%. Inhibition of fast desensitizing currents by Pb2+ was voltage independent and noncompetitive. However, Pb2+ had no effect on acetylcholine-activated single channels in frog muscle fibers. Our results indicate that the hippocampus of the developing rat expresses functional nAChRs of diverse types, and that methyllycaconitine sensitive neuronal nAChRs, which are highly permeable to Ca2+, are much more sensitive to Pb2+ than other nAChR subtypes. PMID- 7791120 TI - Characterization and distribution of binding sites for a new neurotensin receptor antagonist ligand, [3H]SR 48692, in the guinea pig brain. AB - SR 48692, a selective nonpeptide antagonist of neurotensin (NT) receptors was developed recently. In the present work we studied the binding properties of the corresponding radioligand, [3H]SR 48692, in the adult guinea pig brain. The characterization of [3H]SR 48692 binding was carried out on brain membrane preparations and the distribution of [3H]SR 48692 binding sites was determined by receptor autoradiography and compared to that of [125I]NT binding sites. In brain homogenates, [3H]SR 48692 bound to a single population of sites with a Kd of 2.19 nM and a maximal binding capacity of 1.15 pmol/mg of protein. This maximal binding capacity value was 20 times higher than that observed for [125I]NT. NT agonists were able to interact competitively with the entire population of binding sites labeled by [3H]SR 48692, but their affinities were much lower than those observed for [125I]NT. By contrast, NT antagonists exhibited similar abilities to inhibit the binding of both radioligands. The addition of unlabeled NT in saturation assays revealed a competitive inhibition of [3H]SR 48692 binding, suggesting that agonist and antagonist ligand bind to overlapping domains of the NT receptor. The autoradiographic distribution of the low-affinity NT binding sites detected by [3H]SR 48692 (96% of the receptors) was very similar to the distribution of high-affinity receptors labeled with [125I]NT (4% of the receptors). In addition, the binding of [3H]SR 48692 was insensitive to guanyl nucleotides. Taken together, these findings suggest that the binding sites detected by [3H]SR 48692 in the guinea pig brain mainly represent the uncoupled form of the NT receptor. PMID- 7791123 TI - Rotation and striatal c-fos expression after repeated, daily treatment with selective dopamine receptor agonists and levodopa. AB - The available evidence suggests that daily injections of selective dopamine (DA) D2 receptor agonists to DA depleted rats typically leads to behavioral sensitization, but the effects of repeated treatment with selective DA D1 receptor agonists are more equivocal. In this study we examined the effects of acute and repeated treatment with DA receptor agonists with various D1/D2 receptor selectivities on rotation and striatal c-fos activation in rats with unilateral DA depletions. Lesioned rats were treated daily for 10 d with either the novel, selective DA D1 receptor agonist, A-85653, the DA D2 receptor agonist, quinpirole, a combination of these compounds, or the indirect D1/D2 receptor agonist levodopa (L-DOPA). Over days, rats given A-85653 alone showed behavioral tolerance, whereas those given either quinpirole or L-DOPA demonstrated behavioral sensitization. Repeated A-85653 + quinpirole treatment s lead to an increase in response magnitude early in the testing sessions and this was accompanied by a reduction in response duration over days. Quantitative analysis of striatal c-fos activation was also conducted in lesioned rats treated acutely or repeatedly with A-85653, A-85653 + quinpirole or L-DOPA. Numbers of Fos immunoreactive nuclei were sharply reduced after the agonist challenge in all animals given repeated, compared to acute, drug treatment, despite enhanced levels of rotation by rats given quinpirole + A-85653 or L-DOPA repeatedly. These results suggest that desensitization may develop at the DA D1 receptor as a consequence of repeated stimulation, and that the behavioral sensitization seen after repeated L-DOPA treatment may primarily involve the DA D2 receptor. PMID- 7791124 TI - Inhibition of interleukin-1 and tumor necrosis factor-alpha synthesis following treatment of macrophages with the kappa opioid agonist U50, 488H. AB - Previous reports from this laboratory, and others, have shown that exogenous mu and kappa opioids modulate both cellular and humoral immune responses. Our earlier work has suggested that accessory cells may serve as a target for the direct effects of kappa opioid compounds. In the present study, the function of the macrophage cell line P388D1 was modulated by the kappa-selective opioid agoinst U50,488H (trans-3,4-dichloro-N-methyl-N-[7-(1- pyrrolidinyl)cyclohexyl]benzene-acetamide methanesulfonate). Lipopolysaccharide induced interleukin (IL)-1 and tumor necrosis factor-alpha production were inhibited after the administration of nanomolar concentrations of U50,488H. Furthermore, inhibition of IL-1 produced by the P388D1 cell line was reversed by both the classical opioid antagonist naloxone and by the kappa opioid receptor antagonist norbinaltorphimine. Examination of IL-1 mRNA levels in P388D1 by northern blot analysis showed that the inhibition mediated by U50, 488H apparently occurred at the level of transcription. On the other hand, U50,488H failed to modulate the production of IL-6 by this macrophage-like cell line. In addition, U50,488H failed to modulate the production of either IL-1 or tumor necrosis factor-alpha from the macrophage-like cell line RAW 264.7, an indication that subpopulations of macrophages exist with different sensitivities to opioids. These results are consistent with a growing body of data which suggests that a component of the inhibition mediated by opioid compounds involves a reduction in the production of cytokines. PMID- 7791126 TI - Specific transcriptional inhibition of bone marrow-derived macrophage tumor necrosis factor-alpha gene expression and protein production using novel enantiomeric carbocyclic nucleoside analogues. AB - Tumor necrosis factor-alpha (TNF-alpha) is a powerful macrophage-derived proinflammatory cytokine, via both direct effects on host tissues as well as indirectly through the induction of other proinflammatory mediators, including interleukin- (IL) 1 beta and IL-6. Activation of murine bone marrow-derived macrophages (BMDM phi) with lipopolysaccharide (LPS) causes rapid expression of TNF-alpha, which as an autocrine factor enhances BMDM phi function through IL-1 beta and IL-6 production. In this study, we have examined the specific transcriptional inhibition of BMDM phi TNF-alpha using novel enantiomeric carbocyclic nucleoside analogues. BMDM phi were derived in vitro from murine bone marrow progenitors using colony stimulating factor-1 and treated with combinations of LPS (1-100 nG/ml) and the enantiomeric carbocyclic nucleoside (10 100 microM) analogues MDL 201, 112 (9-[(1S,3R)-cis-cyclopentan-3-ol]adenine); MDL 201,451 (9-[1R,3S)-cis-cyclopentan-3-ol]adenine); MDL 201,449 (9-[(1R,3R)-trans cyclopentan-3-ol]adenine) and MDL 201,484 (9-[(1S,3S)-trans-cyclopentan-3 ol]adenine). Northern blot analysis showed that MDL 201,449 was the most effective agent in vitro at selectively inhibiting TNF-alpha. MDL 201,449 reduced TNF-alpha mRNA levels by nearly 50% for up to 4 hr after the simultaneous addition of LPS and the synthetic agent. In contrast, mRNA and secreted protein levels for IL-1 beta (measured by the D10.S bioassay) and mRNA for TNF-alpha receptor p60 and TNF-alpha receptor p80 were not significantly affected. Carbocyclic nucleoside analogues were effective when added to BMDM phi up-to 2 hr after LPS treatment and at concentrations as low as 10 microM. Regulation of BMDM phi IL-6 by carbocyclic nucleoside analogues in response to LPS appears to be both concentration and time dependent, because IL-6 mRNA and secreted protein levels were inhibited at only high drug concentrations (100 microM) and effective only at longer exposure times (+4 hr of incubation) to LPS. These data support the concept that M phi-derived proinflammatory cytokine gene expression is differentially, rather than coordinately, regulated by selective signal transduction and/or molecular pathways. Enantiomeric carbocyclic nucleoside analogues that specifically inhibit TNF-alpha may have therapeutic potential in inflammatory diseases, such as systemic inflammatory response syndrome, where TNF alpha has been shown to have an important role in initiating the early stages of disease. PMID- 7791125 TI - Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. AB - Acetaminophen (APAP) when administered in excess can cause severe hepatic necrosis in vivo. To study the mechanism of APAP toxicity and the role of cytochrome P450, a previously established human hepatoma HepG2 subline, MVh2E1-9, that constitutively expresses human CYP2E1 was used as a model. At high concentrations (above 5 mM) and when intracellular reduced glutathione (GSH) was depleted, APAP caused severe cytotoxicity in MVh2E1-9, but not in MV-5 cells which lack CYP2E1. The APAP cytotoxicity was dependent on the concentration of APAP and time of exposure, and could be blocked by 4-methylpyrazole, ethanol, diallyl sulfide, N-acetylcysteine and N-t-butyl-alpha-phenylnitrone, but not by propylgallate, an inhibitor of lipid peroxidation. Significantly more 14C-labeled APAP protein adduct was detected in MVh2E1-9 cells than MV-5 cells, especially after depletion of GSH. The formation of the APAP adducts could be inhibited by the same agents which prevent APAP cytotoxicity. At a lower concentration (1-2 mM), APAP inhibited proliferation in both MVh2E1-9 and the control MV-5 cells to similar extents. This antiproliferative action of APAP did not require depletion of GSH as did the cytotoxic action of APAP. These data suggest that APAP has a dual toxic effect on MVh2E1-9 cells: a P450-independent antiproliferative effect and the CYP2E1-dependent cytotoxic effect. These results demonstrate the ability of human CYP2E1 to activate APAP to reactive metabolites which form covalent protein adducts and cause toxicity to a hepatoma cell line. PMID- 7791127 TI - Identification of a novel chemical series that blocks interleukin-1-stimulated metalloprotease activity in chondrocytes. AB - Cartilage destruction is one of the essential features of osteoarthritis and other degenerative disease conditions of articular disease, and it may be caused by metalloproteases induced by cytokines such as interleukin-1. To search for novel chemical entities that will block the production of metalloproteases, we have utilized an in vitro system in which macrophage-conditioned medium (a source of interleukin-1) was used to stimulate rabbit articular chondrocytes in culture. Upon treatment with macrophage-conditioned medium or recombinant interleukin-1, chondrocytes synthesize and secrete collagenase, stromelysin and other proteases into the surrounding medium and fail to organize an appropriate extracellular matrix. Using this in vitro system, we have determined that a series of naphthopyran derivatives were able to block the production of neutral metalloproteases. Structural modifications of the lead compound have revealed specific requirements for activity. This class of compounds represents one of very few that are known to block the synthesis, rather than the activity, of matrix-degrading metalloproteases and thus may be beneficial in preventing the cartilage destruction associated with several degenerative diseases of the articular joint. PMID- 7791128 TI - Increase of diazepam binding inhibitor mRNA levels in the brains of chronically ethanol-treated and -withdrawn mice. AB - Although the molecular mechanisms underlying behavioral responses observed in ethanol (EtOH)-dependent and -withdrawn animals are poorly understood, several lines of evidence have suggested that some of the pharmacological actions of EtOH are mediated via the potentiation of gamma-aminobutyric acid (GABA)ergic transmission. In the present study, the effects of acute and chronic EtOH treatment on the expression of diazepam binding inhibitor (DBI) mRNA in the mouse brain and the functional involvement of the benzodiazepine (BDZ) receptor in EtOH induced alteration of the DBI mRNA expression were examined. The expression of cerebral DBI mRNA significantly increased in EtOH-treated (130% of control) and EtOH-withdrawn (220% of control) mice in comparison with untreated mice, whereas the DBI mRNA level was not altered after a single administration of EtOH (3 g/kg i.p.). The increase in the DBI mRNA expression in the mouse cerebral cortex after EtOH withdrawal diminished over 14 days despite the disappearance of withdrawal signs within 2 days after the withdrawal of EtOH. Simultaneous administration of flunitrazepam (10 mg/kg i.p.) with EtOH completely abolished the EtOH-induced increase in DBI mRNA expression. On the other hand, the level of beta-actin mRNA was not affected by similar EtOH treatment. These results indicate that changes in the expression of cerebral DBI mRNA induced by long-term EtOH treatment may be involved in the establishment of alcohol dependence, and such changes may be also regulated by BDZ receptors. PMID- 7791129 TI - Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence-like seizures induced by GHB. AB - The ventrobasal nucleus of thalamus (VB) is considered to be intimately involved in the genesis of experimental absence-like seizures. Bilateral microinfusion of gamma-hydroxybutyric acid (GHB) into VB or systemic administration of gamma butyrolactone, the pro-drug of GHB, induces generalized absence-like seizures in rats. In the present study, the basal and K(+)-evoked extracellular output of endogenous gamma-aminobutyric acid (GABA) and glutamate (GLU) in behaving rat VB nucleus was characterized 1) during unilateral GHB perfusion into VB and 2) during the course of generalized absence-like seizures induced by GHB. Although the basal extracellular release of GABA was inhibited by GHB (250-1500 microM) in a concentration-dependent manner, basal GLU levels remained unaltered. However, K(+)-evoked release of both GABA and GLU was significantly attenuated by GHB. During GHB-induced absence-like seizures, a similar decrease in basal GABA or K(+)-evoked GABA and GLU levels was observed. These effects of GHB were partially reversed by the specific GHB receptor antagonist NCS 382. (-)-Baclofen (10-50 microM) also produced a concentration-dependent decrease in basal and K(+)-evoked levels of GABA and GLU in this thalamic nucleus. The effects of either (-) baclofen or GHB on the release of GABA and GLU were selectively antagonized by the GABAB receptor antagonists phaclofen (0.75-2 mM) and CGP 35348 (50-200 microM), respectively. These results suggest that by selectively modulating the basal and K(+)-evoked release of GABA and GLU, GHB induces, in the thalamic ventrobasal relay nucleus, an optimal "excitatory" environment conducive to the generation of absence seizures. Moreover, the data raise the possibility that a presynaptic GHB/GABAB receptor complex occurs in VB. PMID- 7791130 TI - Specific inhibition of the contraction of the rat aorta by estradiol 17 beta. AB - Short-term exposure to estradiol 17 beta is known to inhibit the contraction of vascular smooth muscle preparations that is thought to be mediated by a [Ca++] dependent mechanism. The purpose of this investigation was to examine the effect of prolonged exposure of vascular preparations to estradiol 17 beta to provide significant time for protein synthesis. We find that treatment of rat aortic rings with estradiol 17 beta (0.37-37 microM) for 15 to 180 min and subsequent removal of the estrogen by washing, attenuated the vasoconstrictor responses to phenylephrine and potassium chloride in a time-dependent manner. The maximum inhibitory effect took 120 min to develop. The inhibitory effect was endothelium independent and not blocked by the cyclooxygenase inhibitor, indomethacin, or by the endothelium derived relaxing factor inhibitor, Nw-nitro-L-arginine methyl ester. This effect was highly stereo-specific in that the 17 alpha isomer was significantly less potent than the 17 beta isomer of estradiol. Further, compared to other steroids, estradiol 17 beta was the most potent. The inhibitory effect of estradiol was blocked completely by pretreatment with the protein synthesis inhibitors, cycloheximide and puromycin, but not by actinomycin D. Electron microscopy showed an increase in ribosomal expression at the rough endoplasmic reticulum after incubation of the rat aorta with estradiol for 120 min. This indicates increased protein synthesis after exposure to estradiol 17 beta. We speculate that the time dependent inhibitory effect of estradiol 17 beta on vascular smooth muscle is related to protein synthesis at the translational level. PMID- 7791132 TI - Opioid tolerance in human placenta due to in vitro methadone administration. AB - Explant culture of term placental villus trophoblast was investigated for its possible use as a model system for study of the effects of chronic methadone administration on binding and functional properties of placental kappa receptors. Viability parameters demonstrated that functional integrity of the tissue and its responsiveness to the modulation of human chorionic gonadotropin release by opioids are fully preserved during the 3 days of culture. Methadone administration for 2 days did not affect the viability of cultured explants. However, it resulted in the development of opioid tolerance, as demonstrated by a shift to the right in the concentration-response curve of U-69,593-induced stimulation of human chorionic gonadotropin release, and irresponsiveness to the inhibitory action of the antagonist nor-binaltorphimine. Kappa receptors of methadone-treated explants exhibited changes in their binding properties that preceded the shift in responsiveness. These data suggest that the development of tolerance to opioids in human placenta starts with an apparent down regulation and change in the affinity of the receptors and may involve downstream events that transduce receptor activation into a biological response. PMID- 7791131 TI - Characterization of human liver microsomal UDP-glycosyltransferases using photoaffinity analogs. AB - The photoaffinity analogs [beta-32P]5-azido-UDP-glucuronic acid ([32P]5N3UDP GlcUA) and [beta-32P]5-azido-UDP-glucose ([32P]5N3UDP-Glc) were used to characterize UDP-glycosyltransferases of microsomes prepared from human liver. Photoincorporation of both probes into proteins in the 50- to 56-kdalton range, known to contain UDP-glucuronosyl transferases (UGTs), was concentration dependent, and photolabeled proteins were susceptible to trypsin digestion only in the presence of detergent. The latter was demonstrated by the appearance on Western blots of the trypsin-treated, detergent-disrupted microsomes of a protein band of slightly lower molecular mass than, and presumably derived from, the UGTs. However, a labeled cleavage product was found only in samples photolabeled with [32P]5N3UDP-GlcUA and not in those labeled with [32P]5N3UDP-Glc. In detergent-treated microsomes, all of the nucleotide sugars that were tested protected better against photoinsertion of [32P]5N3UDP-GlcUA than of [32P]5N3UDP Glc, with UDP-glucose being the most effective, followed by UDP-GlcUA and UDP galactose. The pattern of inhibition of a series of uridinyl analogs toward photolabeling by the two probes was quite different: one inhibitor that was ineffective in blocking photoincorporation of [32P]5N3UDP-GlcUA (L-DPASiU) was one of the most potent inhibitors of photolabeling with [32P]5N3UDP-Glc. A similar dichotomy was seen with several inhibitors in enzymatic assays measuring hyodeoxycholic acid 6-O glucuronidation and glucosidation activities; the most potent inhibitors of HDCA glucosidation were not as effective against glucuronidation. The results indicate a lumenal orientation for human microsomal UGTs and provide substantial evidence that two distinct enzyme systems are involved in 6-O glucuronidation and 6-O glucosidation of HDCA. PMID- 7791136 TI - The plantar arch revisited. AB - In 20 random cadaveric feet, the arterial plantar arch, its anastomosis with the medial plantar artery, and the communication between the lateral plantar and the dorsal arteries of the foot were studied. The anatomic variations found in this material are described and illustrated. The presence of a "classic" anastomosis between the medial and lateral plantar arteries was observed in only 20 percent of cases. The "classic" conjunction of the dorsal artery with the lateral plantar artery was found in 95 percent of cases. The authors conclude that most variations in the contributions to the plantar arch have not been previously reported, and these may have clinical consequences. PMID- 7791133 TI - Benzodiazepine-withdrawal-induced gastric emptying disturbances in rats: evidence for serotonin receptor involvement. AB - This study was performed in rats to determine if serotonin and its receptors are involved in the increase of gastric emptying (GE) induced by benzodiazepine (BZ) withdrawal. GE was measured with a test meal (2 ml) containing 1 microCi/ml of 51Cr sodium chromate administered in rats, either previously receiving injections with diazepam (15 mg/kg/day i.p.) or with DMSO (0.9 ml/day i.p.) during 7 days. On the 8th day, animals received the different serotonin (5-HT) agonists or antagonists, and flumazenil (BZ antagonist; 15 mg/kg i.p.) 30 and 15 min, respectively, before the test meal. Methiotepin (5-HT1 antagonist) either i.p. (0.1-1 mg/kg) or intracerebroventricularly (10 micrograms/kg) had no effect on the increase of GE induced by precipitated-withdrawal. 8-OH-DPAT (5-HT1A agonist) administered i.c.v. (1-10 micrograms/kg) dose dependently reduced GE increase. Administered i.p. (0.1 mg/kg), it blocked GE increase in control and diazepam withdrawn rats. Ritanserin (5-HT2 antagonist) antagonized GE increase only when administered i.p. (0.1 mg/kg). Granisetron (5-HT3 antagonist) was active both i.p. (0.01-0.1 mg/kg) and intracerebroventricularly (1-10 micrograms/kg). Administered intracerebroventricularly (1 microgram/kg) in diazepam-treated rats, 5-HTP mimicked the effect of flumazenil. It is concluded that diazepam-withdrawal increases GE by stimulating central release of 5-HT and/or central activation of 5-HT neurons. At least central 5-HT3 receptors, and in less extend, peripheral 5 HT2 receptors are involved in this mechanism. PMID- 7791134 TI - Revascularization of a seven-week-old infant lower extremity: case report. AB - A seven-week-old infant suffered a closed segmental fracture of the left tibia and fibula complicated by vascular disruption and a secondary compartment syndrome. Initial orthopedic assessment revealed a clinically mottled, cool, pulseless extremity 4 hr post-injury. Radiologic investigations showed multiple displaced fractures of both the tibia and fibula. The infant underwent four compartment fasciotomies and intramedullary nailing of the tibial fractures. The vascularity of the limb failed to improve significantly. Angiograms done 22 hr post-injury revealed disruption of arterial inflow just distal to the bifurcation of the tibial peroneal trunk and posterior tibial artery. Urgent revascularization utilizing a contralateral greater saphenous vein graft was undertaken with a successful outcome. Despite delay in transport from the community hospital and lack of definitive management of the vascular injury, the infant has had a good-to-excellent functional outcome. PMID- 7791135 TI - Bone growth after replantation in children. AB - Bone growth and the development of epiphyseal plates are disturbed after the replantation of amputated extremities in children, but the potential for continued skeletal growth is almost always maintained in the replanted part. In this reported series of 12 children, all younger than 15 years old, 13 amputated parts of the upper limb have been successfully replanted. After long-term follow up (from 21 to 216 months), bone growth of the replanted parts was clinically and radiologically evaluated. Two different growing segments were distinguished: the proximal bone segment, directly injured from the initial trauma, and the distal replanted part. Average longitudinal growth recorded was 94.5 percent and 92.7 percent, respectively. Two young patients demonstrated overgrowth of the proximal bone segment, which attained 110 percent and 118 percent of expected growth. Although it is difficult to determine all the parameters affecting the prognosis of post-traumatic reactions in growing cartilaginous plates, the level of amputation is considered to be a significant prognostic factor for the epiphyseal growth of the replanted part. PMID- 7791137 TI - Anterior chest-wall reconstruction with the extended TRAM double-pedicle free flap: case report. AB - A case of massive, anterior, chest-wall reconstruction is described, utilizing an extended TRAM flap design which was microsurgically transferred on both deep inferior epigastric pedicles, in order to perfuse the flap maximally. The flap is capable of reconstructing the largest chest-wall wounds and should be added to the armamentarium of those reconstructive surgeons involved in the care of these patients. PMID- 7791138 TI - Fibrin glue is a sealant and not a nerve barrier. AB - This experimental work on the internal popliteal nerve of the rabbit was undertaken to clarify whether interposition of a block of 4 mm of fibrin-sealant would form a barrier which stops or interferes with the passage of the axons. Twenty-four adult rabbit tibial nerves were placed in a microclamp, sectioned, and separated 4 mm. The gap between the two nerve ends was filled with fibrin sealant. Eight weeks after the procedure, the animals were sacrificed and the nerves removed. Histologic studies and morphometric longitudinal and transverse examination by image analysis showed that interposition of the block of fibrin sealant between the nerve ends was not a barrier or obstacle to the passage of axons. The use of fibrin sealant is a relatively good experimental model for a chamber of regeneration, because 70 percent of axonal regeneration was obtained. PMID- 7791140 TI - Comparative study between acute intraoperative arterial elongation and the use of the interpositional vein graft for arterial reconstruction. AB - This study compares the acute intraoperative arterial elongation technique with the interposition vein-graft method for the closure of small arterial gaps that cannot be repaired by undermining alone. Ten conditioned female mongrel dogs were divided into two groups: a vein graft interposition group and an acute expansion elongation group. In ten cases, a 25-mm segment of the superficial femoral artery was excised. The resultant defect, measuring 45 to 60 mm, was repaired by an interpositional graft of a comparable size segment of the superficial femoral vein. In ten other cases, a same-size defect was repaired by a tension-free end to-end anastomosis, following acute intraoperative arterial elongation. The animals were explored at various intervals. Overall results revealed a 100 percent patency rate with the acute expansion-elongation group vs. 80 percent with the vein-graft interposition group. The versatility, time saving, and ease of technique, plus previous clinical experience, is encouraging enough to recommend this method for the sound repair of small arterial defects in clinical cases. PMID- 7791139 TI - An easy method of vascular anastomosis for replantation of fingertips. AB - Many cases of successful replantation of fingertips have been reported; however, it still remains difficult for an inexperienced surgeon to anastomose very small vessels (especially veins of the fingertip) because their walls and lumina cannot be clearly defined. The authors report a simple method which is useful for anastomosis of small vessels. A colored silicone background is cut into a small, thread-like segment, and both ends are tapered. This segment is then introduced into the vessel lumen to serve as a vascular stent. The silicone vascular stent makes it easy to identify the vessel lumen and then to suture the vessel edges. It also prevents a through-stitch, the most common cause of anastomosis failure with small vessels. The silicone vascular stent is removed before the last suture is tied. This technique has been used for suturing small veins in the finger pulp or small arteries in zone I, and it will be most helpful for the inexperienced microsurgeon. PMID- 7791141 TI - Improved efficacy of urokinase further prolongs ischemic skin-flap survival. AB - Salvage of a free-tissue transfer, when postoperative vascular compromise is detected, depends largely upon the restoration of a patent microcirculation. The therapeutic efficacy of thrombolytics infused directly into the failing flap has been clearly demonstrated. In this experiment, the authors investigated whether the method of selective administration of urokinase to failing skin flaps in 68 Sprague-Dawley rats had any effect on flap survival. In one group of animals, postischemic flaps were perfused with 100,000 IU of urokinase given by manual injection, and via a pressurized delivery system (150 mmHg) in the other group. Flap survival was assessed at 7 days. A significantly greater survival was seen in flaps treated with urokinase by controlled pressure infusion (p < 0.01). This simple method is suggested to increase the efficacy of urokinase used in the context of flap salvage. PMID- 7791142 TI - Sensory recovery in innervated free-tissue transfers. PMID- 7791143 TI - A 17-year follow-up of replantation of a completely amputated leg in a child: case report. AB - With special reference to skeletal growth, a 17-year follow-up study of a lower leg replantation in a four-year-old boy is reported. The patient maintained good cosmesis and function; however, foot size on the affected side was 1.5 cm smaller than the contralateral side, and leg length was 1.2 cm shorter than on the normal side. A Cybex II study disclosed that the patient had almost half-standard strength of the evertors at 30 deg/sec and of the plantar flexors at 20 and 120 deg/sec on the involved side. According to these findings on late follow-up of a replanted foot in a child, replantation in a growing child apparently has adverse influences on skeletal growth and muscle strength around the ankle joint, even when the original procedure has been carried out under almost ideal conditions. PMID- 7791144 TI - Continuous alteration of the internal milieu of a nerve-guide chamber using an osmotic pump and internal exhaust system. AB - The use of non-neural conduits to span gaps in regenerating peripheral nerves has been noted in the literature for many years. An intriguing addition to this so called entubulation repair method is the continuous instillation of neuronotrophic or growth factors into the lumen of the guide to bathe the regenerating nerve. A model is presented which uses an osmotic pump that supplies a constant, reproducible amount of solution into the lumen of a nerve guide without disrupting the regeneration process. PMID- 7791145 TI - Arteriole constriction following ischemia in denervated skeletal muscle. AB - Arteriolar diameters and flow patterns were determined in the isolated rat cremaster muscle following 4 hr of total ischemia. Two groups of six rats each were studied--an innervated group and a denervated group. The microcirculation was observed using intravital microscopy, and the images were recorded on videotape. The whole arterial tree was scanned, and the smallest vessel diameter for each arterial segment was measured. Preischemic mean arteriole diameters were significantly larger in the denervated group, compared to the innervated group. Following ischemia, during the 3 hr of reperfusion, the main (AI) cremaster arteriole from both the innervated and denervated groups constricted to 50 to 70 percent of pre-ischemic diameters. However, the actual diameters (as distinct from percentage change) were not significantly different between the innervated and denervated groups. There were significant differences in flow patterns. Some A2 and A3 vessels became temporarily nonflowing vessels (either open but without low, or closed by severe spasm). These poorly-functioning vessels were significantly more common in the denervated group. Furthermore, this phenomenon of temporary no-flow persisted longer in the denervated group over the 3-hr reperfusion period. These observations suggest that the ability to recover quickly from an ischemic insult is less in tissues that have been denervated. PMID- 7791146 TI - Classification and diagnostic criteria for polymyositis and dermatomyositis. PMID- 7791147 TI - Is anti-U1-RNP autoantibody positive connective tissue disease genetically distinct? PMID- 7791148 TI - Fibromyalgia 20 years later: what have we really accomplished? PMID- 7791149 TI - Phosphodiesterase inhibitor pentoxifylline: an antiinflammatory/immunomodulatory drug potentially useful in some rheumatic diseases. PMID- 7791150 TI - Minocycline in the treatment of rheumatoid arthritis: relationship of serum concentrations to efficacy. AB - OBJECTIVE: To assess the relationships between serum concentrations of minocycline and clinical efficacy and toxicity during the treatment of patients with rheumatoid arthritis (RA) with minocycline. METHODS: Forty patients with active RA were administered minocycline (maximal oral dose 100 mg twice a day) for 26 weeks. At 3 time points during the treatment, serum samples were collected for measurement of minocycline activity using a microbiological assay. An analysis of variance was performed to estimate an extrapolated concentration at time = 0 (C0) for each patient separately and this value of C0 was regarded to be proportional to the average serum concentration in each patient. The relation between C0 and clinical response and between C0 and the occurrence of adverse effects was evaluated. RESULTS: Minocycline was detected in 96 serum samples from 37 patients. Eighty-two percent of the variance in serum concentrations was accounted for by a model incorporating patient, dose, and time effects. A weak correlation between C0 and clinical response, as expressed by a Ritchie articular index and number of swollen joints, was demonstrated. No correlation was seen between C0 and toxicity, including gastrointestinal or vestibular adverse effects. CONCLUSION: Results suggest a relationship between the serum concentrations of minocycline and the clinical response, including Ritchie articular index and number of swollen joints, in the treatment of patients with RA. No relationship was seen between the serum concentrations of minocycline and its toxicity. PMID- 7791151 TI - Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group. AB - OBJECTIVE: To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA). METHODS: Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment. RESULTS: One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate. CONCLUSION: Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA. PMID- 7791152 TI - An open study of pentoxifylline in the treatment of severe refractory rheumatoid arthritis. AB - OBJECTIVE: Recent data implicates the cytokine, tumor necrosis factor alpha (TNF alpha), in the pathophysiology of rheumatoid arthritis (RA). In vitro data suggest that pentoxifylline may possess anti-TNF-alpha properties. We have therefore carried out a prospective 3-month open evaluation of pentoxifylline in a group of adult patients with RA refractory to conventional disease remittive therapies. METHODS: Nineteen patients with RA were included and clinical assessments were performed according to the World Health Organization/International League of Associations for Rheumatology (WHO/ILAR) criteria at baseline, and one and 3 months after the initiation of therapy. Laboratory assessments included a complete blood count, erythrocyte sedimentation rate (ESR), and whole blood assays of TNF-alpha production. TNF-alpha was assayed using ELISA and semiquantitative polymerase chain reaction methodologies. RESULTS: A significant diminution in number of tender and swollen joints as well as the ESR was noted after 3 months (p < 0.05) although no consistent effects on TNF-alpha production were observed. Furthermore, whole blood assays of TNF-alpha production shortly after initiation of pentoxifylline therapy were not predictive of the clinical response to this agent. CONCLUSION: Although pentoxifylline may possess therapeutic properties in RA, any beneficial effects appear to be unrelated to changes in TNF-alpha generation in whole blood assays. PMID- 7791153 TI - The effects of food on methotrexate absorption. AB - OBJECTIVE: To determine the effects of food on methotrexate (MTX) absorption in patients receiving MTX for the treatment of rheumatoid arthritis (RA). METHODS: Standard pharmacokinetic variables were determined in patients with RA after their usual maintenance dose of MTX, under fasting conditions and after they ate a standard breakfast. RESULTS: No significant differences in area under the serum concentration versus time curve, maximal MTX concentration after dosing (Cmax), time to Cmax), bioavailability, urinary MTX, renal clearance of MTX, or creatinine clearance were observed between the 2 dosing conditions. CONCLUSION: We observed no significant effect of food on MTX absorption or bioavailability. Patients may consume MTX without regard to meals. PMID- 7791154 TI - Influence of low doses of methotrexate on superoxide anion production by polymorphonuclear leukocytes from patients with rheumatoid arthritis. AB - OBJECTIVE: The mechanism of methotrexate (MTX) action in rheumatoid arthritis (RA) is unclear. We assessed the influence of MTX on neutrophil superoxide production evaluated by ferricytochrome c reduction. METHODS: Neutrophils were collected from MTX treated patients with RA (MTX-RA), patients with RA without medication (RA) and healthy donors, cocultured with MTX or MTX-RA serum. RESULTS: Polymorphonuclear leukocytes (PMN) from MTX-RA showed decreased superoxide production when compared with cells collected from patients with RA and controls. Control PMN superoxide production was inhibited (36%) by MTX-RA serum incubation. This reduction was accompanied by clinical improvement. MTX had no activity in the in vitro assays. CONCLUSION: MTX treatment may interfere with neutrophil superoxide production. PMID- 7791155 TI - Comparison of self-reported fatigue in rheumatoid arthritis and controls. AB - OBJECTIVE: To compare self-reported fatigue in adults with rheumatoid arthritis (RA) with age and sex matched healthy controls without RA and to determine the relationships of fatigue to pain, sleep, functional status, depressive symptoms, and disease activity. METHODS: A sample of 51 patients with RA and 46 age and sex matched controls without RA completed self-administered questionnaires 3 times at 6-8 week intervals. Questionnaires included the Multidimensional Assessment of Fatigue scale, Sleep Survey, Health Assessment Questionnaire, and the Profile of Mood States. Patients had blood drawn for hematocrit (Hct) and C-reactive protein on the same day the questionnaires were completed. RESULTS: Fatigue scores were significantly higher in persons with RA compared to healthy controls. Fatigue did not change significantly in either group over time. Fatigue was strongly associated with poor sleep, functional disability, greater pain, more depressive symptoms, and lower Hct. CONCLUSION: The importance of assessing fatigue in RA is confirmed. Effective management is needed to control clinical manifestations of RA that were found to be strongly associated with fatigue such as poor sleep, functional disability, pain, depressive symptoms, and lower Hct. PMID- 7791156 TI - Association of social support and the spouse's reaction with psychological distress in male and female patients with rheumatoid arthritis. AB - OBJECTIVE: To determine if social support and the reaction of the spouse to the patient's pain are contributing factors to psychological distress in male and female patients with rheumatoid arthritis (RA). METHODS: Physical, social, and psychological aspects of health were assessed in 97 male and 132 female patients who were living with a spouse. Differences between male and female patients were analyzed by means of analysis of covariance while controlling for age and duration of RA. In multiple regression analyses the influence of social support and reaction of the spouse concerning psychological distress was determined after age, duration of RA, and physical functioning had been controlled. RESULTS: Criticism of the spouse significantly contributed to anxiety in male patients and to depression and anxiety in female patients. In addition, male and female patients differed in the social support resources that contributed to psychological distress. A relatively low number of friends was associated with depression in males. A relatively low level of potential support was associated with more anxiety in females. CONCLUSION: High levels of criticism of the spouse and low levels of social support are associated with more psychological distress in male and female patients. The number of friends is a social support resource in male patients and potential emotional support a resource in female patients. PMID- 7791157 TI - Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies. AB - OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE. PMID- 7791159 TI - Prevalence of primary Sjogren's syndrome in China. AB - OBJECTIVE: To determine the prevalence rate of primary Sjogren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies were done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sjogren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sjogren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sjogren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed. PMID- 7791158 TI - Circulating interleukin 1 beta and soluble interleukin 2 receptor: evaluation as markers of disease activity in scleroderma. AB - OBJECTIVES: To investigate whether circulating levels of interleukin 1 beta (IL-1 beta) or soluble interleukin 2 receptor (sIL-2R) reflect clinical disease status and response to therapy in scleroderma. METHODS: Plasma IL-1 beta and serum sIL 2R were measured by ELISA in 19 patients with limited cutaneous scleroderma (9 with extraesophageal internal organ involvement), 5 patients with diffuse cutaneous scleroderma and internal organ involvement, and 11 healthy controls, as well as serially over 12 months in 4 patients with scleroderma treated with cyclosporine. RESULTS: IL-1 beta levels were similar in scleroderma and control subject groups. sIL-2R levels were significantly higher in subjects with scleroderma involving internal organs (elevated in 93%), and correlated with erythrocyte sedimentation rate. sIL-2R levels decreased over 12 months in 2 of 4 patients taking cyclosporine in whom other variables remained unchanged. CONCLUSIONS: Elevated serum sIL-2R is a marker of internal organ involvement in scleroderma and warrants further investigation in assessing disease prognosis and response to therapy. PMID- 7791160 TI - Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system. AB - OBJECTIVE: Rheumatologists are often consulted to evaluate patients suspected of having primary angiitis of the central nervous system (PACNS). The diagnostic process relies heavily on interpreting the results of cerebral angiography and brain biopsy. We have assessed the operating characteristics of those invasive modalities in the diagnosis of PACNS: METHODS: The records of 30 consecutive patients referred for the evaluation of possible PACNS were retrospectively analyzed. Patients were evaluated on clinical grounds, and the diagnostic process was extended accordingly until a reasonable probability of a definable disease was present. All patients had cerebral angiography and/or brain biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for each of the following diagnostic tests: cerebral angiography, brain biopsy, cerebrospinal fluid (CSF) examination, and magnetic resonance imaging (MRI). RESULTS: The final diagnostic outcomes were: PACNS in 7, lymphoproliferative disease in 4, infection in 4, demyelinating disease in 2, reversible vasospastic disorder in 6, and a variety of other nonvasculitic conditions in 7. Cerebral angiography had less than 30% specificity and PPV for PACNS: Brain biopsy had limited sensitivity and NPV (53% and 70%, respectively). CSF examination and MRI, although sensitive, lacked specificity. CONCLUSION: In patients suspected of having PACNS, the results of invasive diagnostic modalities should be interpreted with caution. Accurate diagnosis should rarely rely on any single study and should only follow careful clinical, radiographic and pathologic correlation. PMID- 7791162 TI - Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model. AB - OBJECTIVE: To identify markers for severe disease in psoriatic arthritis (PsA). METHODS: Patients with PsA followed prospectively according to a standard protocol over 14 years were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6-month intervals according to a standard protocol. The information was entered into a computer database. Progression in damage was defined as transitions between damage states based on the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. RESULTS: The best model available, based on patient characteristics at the time of being first seen in the psoriatic arthritis clinic suggests that a high number of effusions and of past medications predicts progression in damage, whereas a low sedimentation rate "protects" from such progression. CONCLUSIONS: Evidence of significant inflammation at first visit predicts progression of damage in the future, suggesting that patients with PsA should be offered more aggressive treatment early in the course of their disease. PMID- 7791161 TI - Classification criteria for polymyositis and dermatomyositis. AB - OBJECTIVE: The establishment of classification criteria for polymyositis (PM) and dermatomyositis (DM). METHODS: Questionnaires inquiring about patients with DM, PM, systemic lupus erythematosus, progressive systemic sclerosis and noninflammatory neuromuscular diseases were distributed to the main medical institutes in Japan. Data were collected and analyzed by computer. RESULTS: Among skin lesions of DM, heliotrope rash, Gottron's sign and erythema or purpura on the extensor surfaces of the extremity joints were shown to be distinguishing criteria. In both DM and PM, proximal muscle weakness, muscle grasping and spontaneous pain, nondestructive arthritis or arthralgia, elevated CK or aldolase level, presence of systemic inflammatory signs, myogenic changes on EMG, positive and anti Jo-1 antibody and pathologic findings compatible with inflammatory myositis were distinguishing criteria items. CONCLUSION: When a patient satisfies one of 3 skin lesion items and at least 4 other items, he or she shall be classified as having DM, sensitivity 94.1%. When a patient satisfies at least 4 items other than skin lesion items, he or she shall be classified as having PM, sensitivity 98.9%. Specificity of DM and PM is 95.2%. PMID- 7791163 TI - Gut inflammation in psoriatic arthritis: a prospective ileocolonoscopic study. AB - OBJECTIVE: Some forms of psoriatic arthritis (PsA) are classified as spondylarthropathy, and subclinical gut inflammation is found in spondylarthropathies. Our study was designed to determine if inflammatory gut lesions were also present in PsA, and if the prevalence of subclinical gut involvement was different in the subgroups of this disease. The relationship with HLA subtypes was also determined. METHODS: Ileocolonoscopy was performed on 64 patients with PsA (37 men, 27 women). RESULTS: Inflammatory gut lesions were found in 10 of the 64 patients (16%): in 3 of the 15 patients (20%) with oligoarthritis and in 7 of the 23 patients (30%) with axial involvement. None of the 26 patients with polyarthritis showed these lesions. The prevalence of HLA B27, Bw62, and B17 was significantly raised in our total group of patients with PsA. HLA-B27 and Bw62 were significantly more prevalent in patients with gut inflammation, 60 and 50%, respectively. CONCLUSION: Gut inflammation is only present in PsA subgroups that belong to the spondylarthropathy concept. This suggests that the gut plays a role in the pathogenesis of locomotor inflammation in these subgroups. The prevalence of gut inflammation in psoriatic spondylarthropathy is significantly lower than in nonpsoriatic spondylarthropathies. Consequently, not only the gut but also the skin may be a portal of entry for causative antigens in PsA. PMID- 7791164 TI - Comparative evaluation of adsorption with E. coli on ELISA tests for Lyme borreliosis. AB - OBJECTIVE: To evaluate prospectively in a clinical setting the use of a soluble fraction of E. coli to adsorb nonspecific antibodies which can cause false positive ELISA tests for Lyme borreliosis. METHODS: The patient population tested was obtained from individuals referred to or initially presenting at a pediatric Lyme disease clinic in Wilmington, DE. Patients were followed for a minimum of 6 months subsequent to primary presentation at the clinic. RESULTS: A total of 209 met criteria for study inclusion, 93 of whom were diagnosed as having Lyme borreliosis and 116 of whom had other diagnoses. Results of ELISA tests were compared with different diagnoses and, when available, ELISA results from commercial laboratories. Findings indicate that some commercial laboratories have excessively high rates of false positive results (> 90% of positives were found to be false positives). CONCLUSION: Adsorption with E. coli antigens effectively removed antibodies causing false positive results including those occurring at commercial laboratories and did not cause any significant reduction in assay sensitivity. PMID- 7791165 TI - Clinical and serologic features of Lyme borreliosis in Russia. AB - OBJECTIVE: To describe clinical and serologic features of Lyme borreliosis, particularly the joint abnormalities, in Russian patients. METHODS: Physicians were invited to refer patients with past or present erythema migrans to the Rheumatology Institute in Moscow; field studies were done of residents in an area endemic for Lyme borreliosis, and a serosurvey was conducted of patients with nonspecific neurologic, cardiac, or joint symptoms. Serologic testing was done by ELISA and Western blotting using a strain of Borrelia afzelii, a member of the B. burgdorferi sensu lato complex, recovered from ticks from the field study site. RESULTS: Of 86 patients with erythema migrans, neurologic abnormalities developed in 26 (30%), cardiac involvement in 5 (6%), arthritis or arthralgia in 35 (41%), and acrodermatitis in 2 (2%). Joint involvement was usually characterized by one or a few brief episodes of joint swelling or pain in one large joint at a time. However, 69 of the 86 patients (80%) received antibiotic therapy early in the infection. The majority of patients with active infection had elevated levels of IgM or IgG antibody to B. afzelii by ELISA, and those with late infection often had IgG reactivity with > or = 5 spirochetal proteins, particularly the 37, 39, 41, 60, and 93 kDa antigens. In a serosurvey of 75 patients with facial palsy, atrioventricular block, or arthritis or arthralgia of uncertain cause, 6 had IgG reactivity with > or = 5 spirochetal proteins. CONCLUSION: Lyme borreliosis in Russia is similar to that in other parts of Europe. Brief episodes of arthritis or arthralgia were a common feature of the illness. PMID- 7791166 TI - Lyme arthritis--a common manifestation in a highly endemic area in Sweden. AB - OBJECTIVE: To study the prevalence and the clinical features of Lyme arthritis in a Swedish area highly endemic for Lyme borreliosis. METHODS: Sera from 480 of 540 individuals living in a tick endemic area on an island in southern Sweden were tested by ELISA for IgG antibodies against Borrelia burgdorferi. A questionnaire was completed at the time serum was obtained. Antibody positive individuals who reported joint pain were examined by the authors one year later. RESULTS: Of 90 seropositive individuals, 34 (38%) reported symptoms of chronic or recurrent arthralgia. Of seronegative individuals from the same area 48/390 (12%) reported such complaints (p < 0.001). One year later one of the 34 seropositive patients with arthralgia had died and, of the remaining, 32 still had arthralgia. Lyme arthritis was diagnosed in 11/32 (35%) of these individuals corresponding to a prevalence of 2.3% (95% confidence interval: 1.0-3.6) in the population. The prevalence of other rheumatic disorders did not differ from that found in other areas in South Sweden. Clinical and laboratory findings were in agreement with previous reports of Lyme arthritis. Other manifestations of Lyme borreliosis were found in 6 of the 11 patients with Lyme arthritis. After antibiotic treatment 9/11 (82%) remain free of complaints followed for 6 months or more. CONCLUSION: Our results indicate that arthritis and musculoskeletal symptoms of Lyme borreliosis are as common in highly endemic areas for Lyme borreliosis in Sweden as in similar areas in North America. PMID- 7791167 TI - Chondroitinase ABC affects the activity of intracellular enzymes in rabbit articular cartilage chondrocytes. AB - OBJECTIVE: To determine the response of intrachondrocytic enzymes to specific matrix proteoglycan depletion induced by nonproteolytic enzyme, i.e., chondroitinase ABC. METHODS: The activity of uridine diphosphoglucose dehydrogenase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and succinate dehydrogenase in the patellar cartilage chondrocytes of postpubertal rabbit was measured cytochemically following a single intraarticular injection of chondroitinase ABC. RESULTS: Dose dependent depression of dehydrogenase activity of duration up to 14 weeks was detected in chondrocytes of all cartilage zones. CONCLUSION: Chondroitinase ABC induced marked proteoglycan depletion, which was not associated with light microscopy structural damage. The mechanism(s) by which chondroitinase ABC produces intracellular effects are unknown. PMID- 7791168 TI - Nonsteroidal antiinflammatory drug discontinuation in patients with osteoarthritis. AB - OBJECTIVE: To determine whether discontinuation patterns differed among nonsteroidal antiinflammatory drugs (NSAID) prescribed to treat osteoarthritis (OA). METHODS: In a retrospective cohort study of Health Maintenance Organization enrollees, 1405 patients with OA aged 45 and older who received a new prescription for one of 4 NSAID were followed for 12 months. Survival analysis was used to evaluate time to discontinuation, used here as a relative measure of both drug efficacy and tolerability. RESULTS: Rates of NSAID discontinuation during the study period were high; only 15 to 20% of those started on a study NSAID were still using the same drug at the end of the 12 month followup period. Using a proportional hazards model to adjust for covariates, the risk of discontinuation did not differ when comparing the agent with the longest duration of use, piroxicam (the referent), to enteric coated aspirin [relative risk (RR) 1.10, 95% confidence interval (CI) 0.93 to 1.30]. Adjusted rates of discontinuation were significantly higher for ibuprofen (RR 1.43, 95% CI 1.22 to 1.69) and for naproxen (RR 1.40, 95% CI 1.19 to 1.65) when compared to piroxicam. CONCLUSION: NSAID discontinuation rates are high among patients with OA and risk of discontinuation differed between NSAID, even after controlling for the effects of such variables as age, disease severity, and concomitant therapy. PMID- 7791170 TI - Cognitive behavioral treatment of fibromyalgia syndrome: a followup assessment. AB - OBJECTIVE: In a previous study, we showed that cognitive behavioral therapy (CBT) was effective in the short term treatment of fibromyalgia (FMS). We tested the hypothesis that a pooled index of 10 target psychometric outcomes would show overall improved outcome at longterm followup versus pretreatment. METHODS: Using a quasiexperimental design and validated psychometric instruments, we compared pretreatment psychometric variables with longterm outcomes in the 25 subjects who had completed the earlier study. A distinction was made between target variables the program had specifically addressed and nontarget variables not specifically addressed. RESULTS: Twenty-two subjects participated at a mean of 30 months after discharge from the program. As at short term followup, no nontarget variable changed from pretreatment to longterm assessment. The short term improvement that had been observed in all 10 target variables was maintained in 3 variables at a Bonferroni corrected alpha level of 0.005: worry, p < 0.001; observed pain behavior, p < 0.001; and control over pain, p < 0.002. All 10 target variables changed in the direction of improvement. A pooled index of these 10 variables showed statistically significant improvement from baseline (p < 0.002). CONCLUSION: Our results suggest that CBT may have a role in the longterm treatment of FMS. PMID- 7791171 TI - Fibromyalgia in rheumatology practice: a survey of Canadian rheumatologists. AB - OBJECTIVE: To determine the perceived proportion of fibromyalgia (FMS) among new consultations in rheumatology practices relative to other rheumatologic disorders. METHODS: We conducted a cross sectional random mail survey of 100 Canadian rheumatologists. The sampling frame was the 1991 membership directory of the Canadian Rheumatology Association from which 100 nonpediatric rheumatologists practising in Canada were selected by stratified random sampling. RESULTS: Results from 89 respondents indicate that FMS is perceived to be one of the 3 most common diagnoses among new patient consultations across Canada. Perceived incidence was not affected by urban size or university affiliation of practice. FMS was the only rheumatologic disorder believed by a majority of respondents to have increased in proportion over the past 5 years. CONCLUSION: In Canada, FMS appears to contribute to a high proportion of outpatient care in rheumatology. PMID- 7791172 TI - Measuring shoulder function with the Shoulder Pain and Disability Index. AB - OBJECTIVE: To extend the validity of the Shoulder Pain and Disability Index (SPADI) by (1) making it suitable for telephone administration; (2) determining its convergent validity with other health status measures; and (3) assessing the responsiveness of the SPADI to clinical change. METHODS: Consecutive primary care patients with shoulder discomfort were followed for 3 months. At enrollment, a detailed shoulder specific history was obtained by a trained research assistant, and the Health Assessment Questionnaire (HAQ), the Medical Outcomes Study SF-20 (SF-20), and numeric and visual analog versions of the SPADI were completed by the patient. At 2, 4, and 12 weeks the numeric scaled SPADI was administered by telephone and patients rated globally the change in shoulder discomfort. RESULTS: One hundred and two subjects were enrolled; 96 completed at least one followup assessment and 75 completed all followup assessments. Subjects were men (98%), predominantly white (73%), with a median age of 60 years, and the majority had experienced shoulder discomfort for > 3 months (66%). At baseline the visual analog (VAS) and numeric scaled SPADI were highly concordant (intraclass correlation coefficient = 0.86), and the SPADI correlated substantially with the HAQ (r = 0.61) and the physical functioning (r = -0.50) and pain (r = -0.43) domains of the SF-20. The SPADI delta (baseline-followup) discriminated accurately between subjects who improved versus those who stayed the same or worsened [receiver operating characteristic cure, (ROC) = 0.91, likelihood ratio for improvement = 34]. CONCLUSION: The numerically scaled SPADI is highly correlated with the original VAS version of the SPADI and other measures of health status. The SPADI is responsive to change and accurately discriminates among patients who are improved or worsened. PMID- 7791169 TI - Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients. AB - OBJECTIVE: To evaluate the possible protective effects of misoprostol on renal function in hospitalized elderly patients treated with indomethacin. METHODS: Forty-five hospitalized elderly patients (> 65 years old) who required therapy with nonsteroidal antiinflammatory drugs (NSAID) were randomly assigned to receive either indomethacin, 150 mg/day (Group A), or indomethacin 150 mg/day plus misoprostol at 0.6 mg/day (Group B). Laboratory variables of renal function [serum creatinine, blood urea nitrogen (BUN) and electrolytes] were evaluated before initiation of therapy and every 2 days, until termination of the study (a period of at least 6 days). Response to treatment was estimated by the visual analog scale for severity of pain. RESULTS: Forty-two patients completed the study, 22 in Group A and 20 in Group B. BUN and creatinine increased by > 50% of baseline levels in 54 and 45% of Group A patients, respectively, compared to only 20 and 10% of Group B patients (p < 0.05). Potassium (K) increment of 0.6 mEq/l or more was observed in 50% of Group A, but in only 15% of Group B patients (p < 0.05). The mean increments in BUN, creatinine, and K were reduced by 63, 80, and 42%, respectively, in Group B patients compared to Group A. Response to treatment did not differ significantly between the 2 groups. CONCLUSION: Hospitalized elderly patients are at risk for developing indomethacin related renal dysfunction. Addition of misoprostol can minimize this renal impairment without affecting pain control. PMID- 7791174 TI - The Dunlop-Dottridge Lecture. Ankylosing spondylitis: defining disease status and the relationship between radiology, metrology, disease activity, function, and outcome. PMID- 7791173 TI - The impact of musculoskeletal disorders in the population: are they just aches and pains? Findings from the 1990 Ontario Health Survey. AB - OBJECTIVE: In light of the high frequency of symptoms of musculoskeletal (MSK) disorders in the population, our objective was to establish the impact of these disorders on morbidity and health care utilization. METHODS: Analysis of interview data from the 1990 Ontario Health Survey (sample size 45,650 from the household population age > or = 16 years) has provided one of the first opportunities to relate reported MSK morbidity to disability, illness duration, and use of health services. RESULTS: Overall, MSK disorders were reported as a cause of morbidity or health care utilization by 29% of the population aged > or = 16 years. The prevalence of chronic MSK disorders was 22%; this includes the 5% of the population who reported longterm disability due to MSK disorders. Of reported MSK disorders, 79% had a duration of over 6 months, and the median duration was 5 years. MSK disorders impact in the previous 2 weeks, defined as reduced activity or use of health care (seeing a health professional or taking prescription or nonprescription medication) specifically because of MSK disorders, was reported by 12% of the population, of whom 72% reported chronic MSK disorders. A health professional had been consulted within the previous year for 72% of the reported MSK disorders. The proportion with consultations was over 80% for durations of one year or less, and remained over 50% for disease durations > or = 10 years. CONCLUSIONS: Reported MSK disorders cannot be dismissed as minor problems not requiring ongoing care in view of their long duration, disabling impact, and continuing consumption of health care services and resources. PMID- 7791175 TI - Epidemiology of juvenile rheumatoid arthritis in Manitoba, Canada, 1975-92: cycles in incidence. AB - OBJECTIVE: To determine the yearly incidence of juvenile rheumatoid arthritis (JRA) and to seek correlations between this and cyclic infections occurring in the province of Manitoba, Canada, during the same period. METHODS: An estimate of the incidence of JRA in Manitoba was determined from a disease registry of the Pediatric Rheumatology Clinic, Children's Hospital, Winnipeg. The numbers of confirmed Mycoplasma pneumoniae and viral respiratory infections were determined from annual reports of Cadham Provincial Laboratory. Both facilities provide centralized services for the province. RESULTS: Between 1975 and 1992 the onset of JRA occurred in 261 patients (136 with pauciarticular, 91 polyarticular, and 34 systemic onset). The average annual incidence of JRA for this period was 5.34/100,000. However, a cyclic incidence was apparent with peaks in 1979, 1982, 1986, and 1990-91. Increases in confirmed M. pneumoniae infections were concurrent with peaks in the incidence of JRA. A significant correlation was found between the incidence of JRA and the number of M. pneumoniae infections detected in the province between 1985 and 1992 (R = 0.76, p = 0.044). In contrast, there was no consistent variation in the incidence of seronegative spondyloarthropathies in children (n = 103 patients). CONCLUSION: These data suggest the need for further study of a possible infectious etiology for JRA. PMID- 7791177 TI - Interpretation of immunoblot in pediatric Lyme arthritis. AB - OBJECTIVE: To determine the pattern of bands present on an immunoblot (Western blot) in children with Lyme arthritis. METHODS: Sera from 20 children with Lyme arthritis from an endemic area were assayed, and the results compared with those obtained in 162 control sera from the same area. The study was retrospective, serum bank based. RESULTS: Eighty-seven percent of control sera revealed no bands on immunoblot, and all had < or = 4 bands. All Lyme arthritis sera revealed > or = 5 bands (mean 8.4, range 5-13 bands). Bands of molecular weight 25, 28, 39, 47, 50, and 93 kDa were seen in patients and not in controls. There was no correlation between duration of arthritis or activity of arthritis at presentation and number of bands present. CONCLUSION: Criteria were derived for a positive immunoblot based on the number and molecular weights of bands seen in our laboratory. These are the presence of 5 or more bands, of which at least one is an apparently specific band (25, 28, 39, 47, 50, or 93 kDa). Results of immunoblot are useful to confirm clinically suspected Lyme arthritis. PMID- 7791176 TI - Musculoskeletal disorders in juvenile onset mixed connective tissue disease. AB - OBJECTIVE: We studied the occurrence of musculoskeletal involvement in patients with juvenile onset mixed connective tissue disease (MCTD) and their functional ability. METHODS: Thirteen patients who fulfilled the Kasukawa criteria of MCTD, were subjected to a general orthopedic assessment, as well as to a specific examination of tenderness and swelling of joints, muscle strength, joint motion and alignment, radiographical evaluation, and on disability and discomfort. RESULTS: Low indices were found on the modified Ritchie Articular Index (RI) (0.07) and the Fuchs Swelling Index (0.13). Mild to moderate indices were measured on the Joint Alignment and Motion Scale (JAM) (0.52) and on the Larsen Radiographic Evaluation Scales for the wrist, metacarpal, proximal and distal interphalangeal joints (L-RES) (1.40, 0.62, 0.31, 0.31). The mean pulp-thickness ratio was 22%, which is an indication for sclerodermic changes in the hands. Proximal muscle weakness was found in 10/13 patients (mainly in the upper extremity), distal muscle weakness was found in 12/13 patients. On the pediatric version of the Stanford Health Assessment Questionnaire (C-HAQ), pain and discomfort scored 0.04, disability scored 0.46; those scores were considered to below. Between L-RES and JAM a significant correlation was found (0.74, 0.74 and 0.73; p < 0.01). Another significant correlation was found between the RI and the disability score of the HAQ (0.58; p < 0.05). CONCLUSION: Sclerodermic changes as well as arthritic changes are of a benign character in our population of patients with juvenile onset MCTD. PMID- 7791178 TI - Pulmonary fibrosis and myositis in a child with anti-Jo-1 antibody. AB - This is the first report of a child with anti-Jo-1 antibody. At 10, she had a chronic cough, wheezing, dyspnea on exertion, a combined obstructive and restrictive ventilatory defect, and a decreased diffusion capacity compatible with alveolar fibrosis (lung biopsy). By age 12, she developed arthralgias, malar rash, frontal alopecia, Raynaud's phenomenon, and was seropositive for antinuclear antibodies, (SSA)Ro, Jo-1 and rheumatoid factor. At 16, symptomatic inflammatory myositis (elevated creatinine kinase, muscle biopsy) was documented with persistent anti-Jo-1. Her pulmonary symptoms have progressed despite appropriate therapy. Although her digits have become sausage shaped with swan neck deformities, joint pain is not frequent. PMID- 7791179 TI - Parvovirus B19 associated monoarthritis in a 5-year-old boy. AB - We describe the case of a 5-year-old boy who presented with parvovirus B19 associated arthritis of the left knee lasting for 6 weeks. Other features included flu-like symptoms, a mild "slapped cheek" sign, and a macular, erythematous, lace-like rash over the chest and limbs. The analysis of the synovial fluid showed a high white cell count with a predominance of polymorphonuclear cells. The characteristic features related to parvovirus B19 associated arthropathy in children are reviewed. PMID- 7791180 TI - Fatal myocardial infarction in an 8-year-old girl with systemic lupus erythematosus, Raynaud's phenomenon, and secondary antiphospholipid antibody syndrome. AB - An 8-year-old black girl with a 5 month history of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) developed Raynaud's phenomenon, marked hemolytic anemia, and a fatal myocardial infarction (MI). Pathologic evaluation of the heart demonstrated a transmural acute MI associated with a recent thrombus of the circumflex coronary artery, thrombosis of small intramural arteries, and a coronary arteriopathy resembling fibromuscular dysplasia. Inflammatory or atherosclerotic changes of the coronary arteries were distinctly absent. This case represents the youngest reported patient with SLE, MI, and pathologic confirmation of nonatheromatous coronary artery disease. The observed coronary pathological findings may have accentuated the thrombogenic potential of the APS, resulting in coronary thrombosis. Cardiac lesions in SLE and APS are reviewed, and pathogenetic considerations for the coronary vasculopathy are discussed. PMID- 7791181 TI - Bilateral juvenile temporal arteritis. AB - Juvenile temporal arteritis (JTA) is an uncommon nongiant cell arteritis of the superficial temporal artery occurring exclusively in older children and young adults without a history of trauma or evidence of systemic disease or localized symptoms. Of the 6 cases reported to date, there has been no recurrence after a simple surgical excision of the nodular artery for cosmetic reasons. We describe the first known case of bilateral JTA in a 21-year-old man and differential diagnoses are discussed to distinguish JTA from the classic giant cell (temporal) arteritis of the elderly, which requires corticosteroid drug treatment. PMID- 7791182 TI - Progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis and polymyositis. AB - We describe a young woman who developed postpartum rheumatoid arthritis, polymyositis and small vessel cerebrovascular disease. Subsequently she developed biopsy proven progressive multifocal leukoencephalopathy (due to JC virus infection) which may have been a complication of her immunosuppression. This rare complication of autoimmune rheumatic diseases is discussed. PMID- 7791183 TI - Central nervous system angiopathy associated with cocaine abuse. AB - Cocaine abuse has been associated with various cerebrovascular complications, including vasculitis. We describe a patient who presented with neurologic defects associated with cocaine abuse. Although angiography raised the suggestion of vasculitis, biopsy revealed a lack of inflammatory changes, and other aspects of the clinical course also militated against inflammatory vasculitis. This case was reminiscent of recently described patients initially suspected of having primary central nervous system (CNS) vasculitis but subsequently considered to have "benign angiopathy." We suggest that benign angiopathy of the CNS can occur as a result of cocaine abuse. PMID- 7791184 TI - Posttraumatic reflex sympathetic dystrophy anteceding inverse psoriasis and psoriatic arthritis. AB - We describe a patient wit posttraumatic reflex sympathetic dystrophy involving the right hand who subsequently developed inverse psoriatic skin lesions and psoriatic arthritis in the injured hand as well as in other joints. PMID- 7791185 TI - Listeria monocytogenes infection in a patient treated with methotrexate for rheumatoid arthritis. AB - We describe a patient with rheumatoid arthritis who developed bacteremia from Listeria monocytogenes after treatment with low dose oral pulse methotrexate. We discuss possible immunologic mechanisms for susceptibility to Listeria infections. As the elderly population increases with more frequent use of immunosuppressive medications, clinical suspicion must be maintained to correctly diagnose and treat infections such as Listeria. PMID- 7791186 TI - The clinical and research significance of the erythrocyte sedimentation rate. PMID- 7791187 TI - Extraarticular manifestations during methotrexate therapy for rheumatoid arthritis. PMID- 7791188 TI - Demography of a regional pediatric rheumatology patient population. PMID- 7791189 TI - Antineutrophil cytoplasmic autoantibodies in systemic sclerosis with renal failure. PMID- 7791190 TI - Myasthenia gravis and scleroderma. PMID- 7791191 TI - Norfloxacin induced arthralgia. PMID- 7791192 TI - Sex ratios and age at onset in probands and secondary cases in the spondyloarthropathies. PMID- 7791193 TI - Rheumatic diseases in China. PMID- 7791194 TI - Listeriosis in patients with connective tissue disease. PMID- 7791195 TI - Gynecomastia following low dose methotrexate therapy for rheumatoid arthritis. PMID- 7791197 TI - Fatal disseminated herpes simplex II infection in a patient with systemic lupus erythematosus. PMID- 7791196 TI - Evidence for bone resorption in systemic sclerosis. PMID- 7791199 TI - Cardiac valve replacement and antiphospholipid antibodies. PMID- 7791198 TI - Successful use of nitrogen mustard for cyclophosphamide resistant diffuse proliferative lupus glomerulonephritis: report of 2 cases. PMID- 7791200 TI - Propylthiouracil therapy: an unusual cause of antineutrophil cytoplasmic antibody associated alveolar hemorrhage. PMID- 7791201 TI - Bubonic plague: doubts and diagnoses. PMID- 7791202 TI - Evidence of Pneumocystis carinii in cell line cultures infected with peripheral blood mononuclear cells isolated from AIDS patients with P. carinii pneumonia. AB - The detection of Pneumocystis carinii was investigated in an in-vitro system consisting of a human lung epithelial cell line (A-549) inoculated with infected peripheral blood mononuclear cells (PMBC) from HIV-infected patients with proven or suspected P. carinii pneumonia (PCP), and from HIV-negative patients with other lung infections. Supernates from cultures were sampled daily and evaluated for the presence of P. carinii by Giemsa and immunofluorescence staining. P. carinii was isolated from 98 (95.1%) of 103 culture supernate samples from patients with proven pneumocystosis and 45 (66.1%) of 68 from patients with suspected PCP 40 or 72 h after PBMC inoculation. This system has been shown to support the growth of P. carinii but did not seem to be adequate for the production of large numbers of organisms, although long-term survival in vitro for up to 3 weeks was observed. Recovery of P. carinii from infected PBMC strongly supports previous observations about its ability to disseminate haematogenously and could represent a further advance in understanding the pathogenesis and diagnosis of PCP. PMID- 7791203 TI - Presence of lysogenic phage in the outbreak strains of Vibrio cholerae O139. AB - Four outbreak strains of Vibrio cholerae O139 from endemic areas of India and Bangladesh were found to carry lysogenic phage(s). All of these phage(s) produced turbid plaques characteristic of lysogeny on V. cholerae MAK 757 (El Tor, Ogawa) cells as well as on their VcA-1 lysogens but were unable to infect V. cholerae 154 (classical) cells, the universal host for all classical phages. Colonies in the turbid plaques were O139 lysogens and these developed an auxotrophic requirement, mainly for purines suggesting the integration of the prophage into the host chromosome. The immunity profile of the O139 phage(s) was similar to that of phage alpha but differed in the sensitivity of the phage lysogen of V. cholerae MAK 757 to subsequent infection by phage beta. PMID- 7791204 TI - Genotyping of Shiga-like toxin genes in non-O157 Escherichia coli strains associated with haemolytic uraemic syndrome. AB - The pheno- and genotypes of Shiga-like toxins (SLTs) in non-O157 Escherichia coli strains from patients with haemolytic uraemic syndrome were determined. The clinical isolates investigated were from Italy and Germany and belonged to serotypes O22:H8, O26:H-, O26:H11, O91:H-, O111:H- and O128:H-; one isolate was non-typable. SLT genotypes were analysed by complete nucleotide sequence analysis of the B-subunit genes. The results showed that 14 strains possessed slt-I alone, two contained slt-II alone and five isolates harboured both slt-I and slt-II genes. In only two strains were slt-II-related genes found, together with either slt-I or slt-II. These findings indicate that variants of SLT-II are rarely found in non-O157 E. coli isolates from patients with haemolytic uraemic syndrome. Polymerase chain reaction (PCR) with Taq cycle sequencing was found to be a suitable method for classification of slt genotypes. PMID- 7791205 TI - Human immunodeficiency virus type-1 can be detected in monocytes by polymerase chain reaction. AB - Lymphocytes and monocytes from 25 patients infected with human immunodeficiency virus type-1 (HIV-1)--13 asymptomatic, seven with the AIDS-related complex (ARC) and five with the acquired immunodeficiency syndrome (AIDS)--were lysed and subjected to PCR with three primer pairs: SK38/SK39 (gag), SK68/SK69 (env) and SK29/SK30 (LTR). Amplified DNA was solution-hybridised with 32P-labelled probes (SK19, SK70 and SK31, respectively) and detected by PAGE-autoradiography. HIV-1 DNA was detected as follows. Asymptomatic patients: monocytes--gag 61.5%, env 100%, LTR 0%; lymphocytes--gag 100%, env 92.3%, LTR 53.84%. ARC patients: monocytes--gag 71.4%, env 57.1%, LTR 0%; lymphocytes--gag 100%, env 71.4%, LTR 71.4%. AIDS patients: monocytes--gag 80.0%, env 100%, LTR 0%; lymphocytes--gag 100%, env 60%, LTR 60%. The presence of HIV-1 DNA was confirmed in the monocyte fraction. In this cell subset, the env gene-directed primers were the most effective for amplification, whereas the LTR gene-directed primers failed to amplify HIV-1 DNA. The different pattern of amplification found in monocytes may suggest that these cells could be infected by a genetic variant of the virus. PMID- 7791206 TI - Electronmicroscopic investigation of the effects of biocides on Pseudomonas aeruginosa PAO bacteriophage F116. AB - Electronmicroscopy was used to observe morphological changes of the Pseudomonas aeruginosa PA0 bacteriophage F116 when treated with various biocides commonly used as antibacterial and antifungal agents. Because of its large size (145 nm) and its organised structure (an isometric head and a tail), it was possible to classify structural damage into eight categories. The morphological changes induced depended on the type of biocide used and its concentration. Glutaraldehyde increased the number of phages with empty heads. Peracetic acid and phenol altered the appearance of the viral genome packaged inside the head, produced fractured heads, and damaged the tail. Peracetic acid also induced folding of the phage heads. The alcohols tested also altered the head structure. Cetylpyridinium chloride induced mainly fractured head damage. Chlorhexidine had little effect on the structure of F116. PMID- 7791207 TI - Antibiotic susceptibility of Mycoplasma fermentans strains from various sources and the development of resistance to aminoglycosides in vitro. AB - Mycoplasma fermentans strains reputedly from human infections or tissue culture cells were much more susceptible to azithromycin than to clarithromycin or erythromycin. Lincomycin, clindamycin and several tetracyclines also exhibited good mycoplasmastatic activity but mycoplasmacidal concentrations were substantially greater than the MICs. Ciprofloxacin was the most active of three fluoroquinolones tested and was mycoplasmacidal at concentrations close to the MIC. Tiamulin and mupirocin were also very active. Synergy with specific M. fermentans antiserum plus guinea-pig complement was not observed with any class of antibiotic although the number of viable mycoplasmas was markedly reduced by the combined immunological components. Marked differences in susceptibility to various aminoglycosides were observed. Human strains isolated in cell-free media up to 1967 were aminoglycoside susceptible (MIC range 0.5-25 mg/L) but recent human isolates and strains isolated from tissue culture cells often showed either single or multiple aminoglycoside resistance (MIC > 500 mg/L). Two aminoglycoside susceptible strains developed resistance to streptomycin or neomycin (> 500 mg/L) within five passages in broth containing streptomycin or neomycin, respectively. Resistance to tobramycin, kanamycin or gentamicin emerged after seven, eight and 14 cycles of exposure to the respective antibiotic. Streptomycin resistance was associated with a five-fold increase in resistance to tobramycin. Neomycin-, kanamycin-, gentamicin- and tobramycin-resistant variants showed mutual cross resistance but remained susceptible to streptomycin. Induced resistance persisted for at least 17 passages in aminoglycoside-free broth. The use of aminoglycosides in human medicine and the frequent inclusion of some of these drugs in tissue cell cultures to combat bacterial and mycoplasmal contamination might account for the aminoglycoside resistance of recent M. fermentans isolates. PMID- 7791208 TI - Back mutations to the TEM-1 beta-lactamase from TRC-1 lead to restored sensitivity to clavulanic acid. AB - Back mutations from the TRC-1 beta-lactamase to the TEM-1 enzyme were selected in vitro. The revertant beta-lactamase was obtained from Escherichia coli strain J62.2 carrying plasmid pUK901 which encodes the TRC-1 beta-lactamase. The revertant was obtained after repeated subculture of E. coli J62.2 (pUK901) in amoxycillin 512 mg/L for 5 days. The revertant beta-lactamase had the same pI as TEM-1 (5.4) and had restored inhibition by clavulanic acid (ID50 reduced from 4.2 microM to 0.15 microM). The prevalence of these beta-lactamases in the clinical population may be the result of a two-way flux, with mutations in both forward and backward directions. PMID- 7791209 TI - Experimental Legionnaires' disease in SCID-Beige mice reconstituted with human leucocytes. AB - A new small animal model of experimental Legionnaires' disease is described in which the reconstitution of SCID-Beige mice with human peripheral blood leucocytes permits the in-vivo growth of Legionella pneumophila in the lungs of aerosol-challenged mice. Following infection, viable bacterial counts within the lungs of mice increased from 10(5) cfu/lung at the time of inoculation to a maximum of 10(10) cfu/lung by 48 h post-inoculation. Two types of disease were detected in the lungs of infected SCID-Beige mice. An acute exudative bronchiolitis and bronchopneumonia were seen in the most severely affected mice and, in the less severely affected mice, lesions of subacute or chronic disease were seen with thickening of alveolar walls and consolidation of lung tissue. Human cells did not appear to be involved directly in the pathology but were required for the establishment of infection. Immunohistological staining of lung tissue revealed substantial amounts of bacterial antigen distributed in a pattern similar to that seen in human Legionnaires' disease. PMID- 7791210 TI - Identification and typing of pyogenic streptococci by enzyme electrophoretic polymorphism. AB - Polyacrylamide-agarose gel electrophoresis was used to study polymorphism of lactate dehydrogenase (LDH), nucleoside phosphorylase (NSP), phosphoglucose isomerase (PGI), hydroxybutyrate dehydrogenase (HBD), adenylate kinase (ADK) and esterases of 44 strains of Streptococcus pyogenes, 25 group G streptococcal strains, 11 "S. equisimilis" strains, seven S. dysgalactiae strains, four S. canis strains, three S. equi strains and seven S. zooepidemicus strains. Analysis of LDH, NSP, PGI, HBD and ADK provided valuable interspecies differentiation, by showing that four groups of strains corresponded to the four known DNA homology groups. Esterases showed greater intraspecies variation than the other enzymes. The combined analysis of the six enzymes indicated 31 zymotypes among S. pyogenes, 14 in group G streptococci and 11 in "S. equisimilis" strains. This was shown to be an effective technique for typing pyogenic streptococci. PMID- 7791211 TI - Crystal structure of the human cell cycle protein CksHs1: single domain fold with similarity to kinase N-lobe domain. AB - The structure of the human CksHs1 homolog of the yeast cell-cycle regulatory proteins suc1 and CKS1, which bind to the catalytic subunit of the cyclin dependent kinases (Cdks) and are essential for yeast cell-cycle progression in vivo, has been determined at 2.9 A resolution. The CksHs1 single polypeptide domain fold, which consists of a four-stranded beta-sheet flanked by two alpha helices, is dramatically different from the subunit conformation and assembly of the homologous CksHs2, but strikingly similar to the Cdk N-lobe domain fold. The CksHs1 structure identifies sequence-conserved residues Glu61 to His65 as a novel beta-hinge region that folds back to form a beta-hairpin with CksHs1 subunit, whereas this hinge is unfolded to form an extended beta-strand exchange between two CksHs2 subunits. Phosphate and the phosphate analog metavanadate bind CksHs1 in a shallow pocket and interact with five conserved residues (Lys11, Arg20, Ser51, Trp54 and Arg71) suggesting a specific Cks recognition site for a phosphorylated Cdk residue. The dramatic changes to the Cks fold, assembly and exposed conserved surface brought about by switching between the bent and extended hinge conformations are potentially important for the functions of this Cks homolog and could explain conflicting activities inferred from different types of genetic experiments. PMID- 7791212 TI - Phage T4-coded Stp: double-edged effector of coupled DNA and tRNA-restriction systems. AB - The optional Escherichia coli prr locus encodes two physically associated restriction systems: the type IC DNA restriction-modification enzyme EcoprrI and the tRNA(Lys)-specific anticodon nuclease, specified by the PrrC polypeptide. Anticodon nuclease is kept latent as a result of this interaction. The activation of anticodon nuclease, upon infection by phage T4, may cause depletion of tRNA(Lys) and, consequently, abolition of T4 protein synthesis. However, this effect is counteracted by the repair of tRNA(Lys) in consecutive reactions catalysed by the phage enzymes polynucleotide kinase and RNA ligase. Stp, a short polypeptide encoded by phage T4, has been implicated with activation of the anticodon nuclease. Here we confirm this notion and also demonstrate a second function of Stp: inhibition of EcoprrI restriction. Both effects depend, in general, on the same residues within the N-proximal 18 residue region of Stp. We propose that Stp alters the conformation of EcoprrI and, consequently, of PrrC, allowing activation of the latent anticodon nuclease. Presumably, Stp evolved to offset a DNA restriction system of the host cell but was turned, eventually, against the phage as an activator of the appended tRNA restriction enzyme. PMID- 7791213 TI - Immunity determinant of phage-plasmid P4 is a short processed RNA. AB - In the phage-plasmid P4, both lysogenic and lytic functions are coded by the same operon. Early after infection the whole operon is transcribed from the constitutive promoter PLE. In the lysogenic condition transcription from PLE terminates prematurely and only the immunity functions, which are proximal to the promoter, are thus expressed. Fragments of the P4 immunity region were cloned in an expression vector. A DNA fragment as short as 91 bp was sufficient, when transcribed, to express P4 immunity and to complement P4 immunity deficient mutants. This fragment, like prophage P4, produced a 69 nt long RNA (CI RNA). A shorter P4 fragment neither expressed immunity nor synthesized the CI RNA. Thus the CI RNA is the P4 trans-acting immunity factor. The 5' end of the CI RNA, mapped by primer extension, does not correspond to the transcription initiation point, thus suggesting that the CI RNA is produced by processing of the primary transcript. In an RNase P mutant host the processing of the 5' end and the production of a functional CI RNA were impaired. The requirement of RNase P for the correct processing of CI appears to be related to the predicted secondary structure of the precursor CI RNA. A region (seqB) within the CI RNA shows complementarity with two cis-acting sequences (seqA and seqC) required for P4 immunity, suggesting that transcription termination may be caused by pairing of the CI RNA with the complementary target sequences on the nascent transcript. PMID- 7791214 TI - Differential regulation of Hox C6 in the appendages of adult urodeles and anurans. AB - Morphogenesis and pattern formation are biological processes that rely on the expression of positional determinants to divide the embryo into compartments. Hox genes are among the selector genes that direct the mechanism of positional information. Here we report the molecular structure and pattern of expression of a new Hox C6 transcript in the adult newt. Molecular analysis showed that the gene transcribes a long primary transcript in both limb and tail regeneration territories and subsequently uses maturation events to produce two RNAs that share the same DNA binding domain and differ in their 5' extremity. Both RNAs were found in the limb and showed a proximal-distal gradient of expression. The tail sample showed accumulation of only one Hox C6 transcript. These results suggest that both transcriptional and post-transcriptional regulations are involved in the appendage-specific expression of Hox C6 in the adult newt. Finally, the adult frog, which has lost its regeneration capacity, also post transcriptionally regulates the expression of Hox C6 in its appendages. PMID- 7791215 TI - Nag repressor-operator interactions: protein-DNA contacts cover more than two turns of the DNA helix. AB - The NagC repressor binds to two sites in the intergenic nagE-B region overlapping the divergently expressed nagE and nagB promoters. In addition the NagC repressor binds to two sites upstream of the manXYZ operon. Although basically palindromic, there is little sequence consensus between the four operators. To identify the DNA sequence important for NagC recognition, we have taken advantage of the fact that repression of the nagE and nagB genes requires the formation of a loop of DNA between molecules of the repressor bound to the nagE and nagB operators. The nagE operator was systematically mutagenised and the effect of the mutations measured on the level of expression from a nagB-lacZ fusion. These experiments showed that the most important positions for recognition are the two A.T base pairs at positions-5 and -6 from the centre of symmetry. These are the only absolutely conserved bases in the four operators. Certain changes of residues at position -3 and -4 have fairly strong effects while changes at -7 to -10 have only minor effects. However the presence of a G or C base at positions + 11 or 11 produces a NagC binding site with considerably higher affinity than the wide type nagE operator both in vitro and in vivo, a "super-operator". The presence of a super-operator considerably increased the stability of the binary looped NagC DNA complex in vitro. However in the presence of cAMP/CAP, NagC showed the same apparent binding affinity to wild-type and super-operators indicating that one role of cAMP/CAP in the repression complex is to reduce the need for high affinity sites. These super-operators allow a higher level of repression of the nagE promoter compared to the nagB, presumably due to the existence of linear complexes of NagC bound to BoxE. PMID- 7791216 TI - N-2-aminofluorene and N-2 acetylaminofluorene adducts: the local sequence context of an adduct and its chemical structure determine its replication properties. AB - The strong rat liver carcinogen, N-2-acetylaminofluorene, forms mainly two types of guanine adducts at the C-8 position, the acetylaminofluorene adduct (dGuo-C8 AAF) and the aminofluorene adduct (dGuo-C8-AF). We have constructed different oligonucleotides bearing a single AF lesion at each of the guanine residues of the NarI mutagenesis hot spot (G1G2CG3CC) and analysed the structural distortion induced by this DNA adduct according to the sequence context. At position G1 and G2, the deformation induced by the AF adduct is smaller than the deformation induced by the corresponding acetylated form of this adduct (i.e. the AAF adduct at the G1 and G2), whereas both AF and AAF adducts induce a similar structural change when bound to G3. Single-stranded oligonucleotides modified with AF adducts were used in primer extension replication assays using purified DNA polymerases (PolIII holoenzyme, Klenow fragment (exo+ and exo-), Sequenase 2.0) and the data compared to the AAF containing substrates. Translesion synthesis (complete bypass) is found with all tested polymerases when AF adducts are bound to G1 or G2 while little or no bypass is seen when the AF adduct is bound to G3. On the other hand, irrespective of its position within the NarI sequence, AAF adducts completely block DNA synthesis. The results described in this paper show that the sole knowledge of the chemical structure of an adduct neither determines uniquely the conformational change it induces at the DNA level nor its replication properties. Indeed, although AF adducts are in most cases non distorting adducts and as a consequence non-replication blocking lesions (as exemplified by adducts at G1 or G2), some AF adducts (as at position G3) behave almost as AAF adducts in terms of the structural distortion induced and its replication blocking property. These findings stress the strong modulation by the local sequence context of the structural and biological consequences of a given adduct. PMID- 7791217 TI - The action of Escherichia coli endonuclease III on multiply damaged sites in DNA. AB - Energy deposition by ionizing radiation can lead to the formation of clustered DNA damage, i.e. more than one lesion situated within a helical turn of DNA. Among the postulated lesions are those characterized by damaged bases and abasic sites on opposite strands. Enzymatic removal of such lesions may inadvertently lead to the formation of double-strand breaks. To test this hypothesis, we have constructed model substrates containing damaged bases (5,6-dihydrothymine) or abasic sites set one, three, five and seven bases apart on opposite strands, and examined the reactivity of Escherichia coli endonuclease III towards these substrates. Endonuclease III demonstrates two activities; as a glycosylase that removes saturated pyrimidine bases, such as dihydrothymine, and as an AP lyase that cleaves DNA strands at abasic sites. Analysis of endonuclease III-treated dihydrothymidine containing plasmid DNA by agarose gel electrophoresis indicated that the enzyme generated only single-strand breaks when the base damage was set one and three base-pairs apart, and only slowly introduced double-strand breaks in the other substrates. Endonuclease III treatment of the abasic site-containing DNA, however, readily yielded double-strand breaks. Taken together, these results indicate that the glycosylase activity of the enzyme, but not the AP lyase activity, is inhibited by the presence of a closely positioned break in the opposite strand. PMID- 7791218 TI - Predicting Pol II promoter sequences using transcription factor binding sites. AB - A computer program, PROMOTER SCAN, has been developed to recognize a high percentage of Pol II promoter sequences while allowing only a small rate of false positives. A total of 167 primate Pol II promoter sequences, obtained from the Eukaryotic Promoter Database, and 999 primate non-promoter sequences, obtained from the GenBank sequence databank, were used in the analysis. Both promoter and non-promoter sequences were analyzed for the comparative density of each unique mammalian transcription factor binding site listed in the Ghosh Transcription Factor Database. The density of each of these binding sites was then used to derive a ratio of density of each transcriptional element in promoter compared to non-promoter sequences. The combined individual density ratios of all binding sites were then collectively used to build a scoring profile called the Promoter Recognition Profile. This profile, used in combination with a weighted matrix for scoring a TATA box, was then used by the PROMOTER SCAN program to test the prediction of promoter sequences and the ability of the computer program to discriminate them from non-promoter sequences. When the promoter cutoff score was set so that 70% of promoters were recognized correctly by the program, a false positive rate of about 1/5600 bases was observed in the non-promoter sequence set. PROMOTER SCAN is now being developed for public distribution. PMID- 7791219 TI - Crystal structure of Proteus mirabilis PR catalase with and without bound NADPH. AB - A catalase from a peroxide resistant mutant of Proteus mirabilis binds NADPH tightly. Interestingly, this enzyme can be stripped of NADPH without loss of the catalatic activity. It is the only known non-mammalian catalase able to bind NADPH. The structure without cofactor was solved by molecular replacement using the structure of beef liver catalase as a model. The structure was refined to an R-factor of 19.3% in the range 8 to 2.2 A resolution. According to the sequence, a methionine sulphone was positioned in the haem active site. This oxidized form of methionine is particular to Proteus mirabilis catalase and likely to produce some steric hindrance in the active site. Two important water molecules are positioned in the haem distal site. These two water molecules are not located in the structure of beef liver catalase, but are supposed to account for the catalytic mechanism. The liganded form was obtained by soaking crystals of the unliganded form into an NADPH solution. The structure was refined to an R-factor of 15.9% in the range of 8 to 3.1 A resolution using the unliganded structure as a model. The NADPH was clearly located in the electron density map with the same conformation as in beef liver catalase. The NADPH binding induces slight structural changes. However, the imidazole ring of a histidine residue (His284) rotates about 50 degrees to accommodate the cofactor. The electron transfer from NADPH to the haem molecule was examined and several pathways are proposed. PMID- 7791220 TI - Computer modelling of the alpha-helical coiled coil: packing of side-chains in the inner core. AB - In order to predict the structure of alpha-helical coiled-coil proteins from their sequences, it is necessary to know how the side-chains pack in the interface between the alpha-helical strands. Since in alpha-fibrous proteins leucine is the most common residue at both the a and d positions of the heptad repeat, which form the inner core of the interface, we determined the lowest energy conformation for a two-stranded coiled-coil with the sequence (LAALAAA)5. Coiled-coils were constructed using the Crick equations with a range of pitches, major helical radii and relative rotations of the two strands, and with different starting side-chain conformations. On energy minimisation, convergence occurred to a small number of structures. The lowest-energy coiled-coil had 2-fold rotational symmetry, an average pitch of 131 A and an average radius of 4.52 A; the leucine side-chain conformations were tt and g+t at the a and d positions. This coiled-coil was used as a former to determine the lowest-energy side-chain conformations for the 63 combinations of a and d residues that occur in the repeating heptad sequence of rat skeletal myosin. The leucine residues at the a and d positions of the central heptad were replaced by the a-d pair of interest and molecular dynamics simulations performed to allow the side-chains of these residues to explore conformational space. The lowest-energy side-chain conformation of a residue at an a or d position depends on the nature of the partnering residue, consistent with the fact that these side-chains pack against one another. In most cases the lowest-energy structure was symmetric but in a few cases the side-chains were asymmetrically disposed in the two strands. The local pitch is very sensitive to the nature of the residues in the inner core and varies over a twofold range. In contrast, the radius and relative rotation of the two strands were relatively insensitive to sequence. PMID- 7791221 TI - Cancer causes revisited: human papillomavirus and cervical neoplasia. PMID- 7791222 TI - Colony-stimulating factors and neutropenia: intersection of data and clinical relevance. PMID- 7791223 TI - Managed care brings major changes to cancer care. PMID- 7791224 TI - Getting a handle on ASCUS: a new clinical trial could show how. PMID- 7791225 TI - Novel technologies for cervical cancer screening seen on the horizon. PMID- 7791227 TI - Many Italian researchers say they can't go home again. PMID- 7791226 TI - Monkey diet may hold clues for finding anti-HIV drugs. PMID- 7791228 TI - New cancer strategies needed for changing population. PMID- 7791229 TI - Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. AB - BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs. PMID- 7791230 TI - Macrophage colony-stimulating factor complementary DNA: a candidate for gene therapy in metastatic melanoma. AB - BACKGROUND: At present, there is no highly effective treatment for metastatic melanoma. Innovative approaches aimed at inducing a more effective immune response against tumors have shown promising results in animal models. One approach involves the genetic modification of tumor cells so that they produce cytokines that stimulate an immune response. PURPOSE: The aim of this study was to determine the effectiveness of cytokine gene therapy for metastatic melanoma in a murine melanoma model. METHODS: B16F10 murine melanoma cells, which readily metastasize to the lungs, were transduced with a retroviral vector containing genes encoding neomycin resistance and human macrophage colony-stimulating factor (M-CSF). The presence of M-CSF messenger RNA in transduced cells was examined by coupled reverse transcription and polymerase chain reaction. Concentrations of soluble M-CSF in cell culture supernatants were determined by enzyme-linked immunosorbent assays (ELISAs). A clonal cell line, designated N+/CSF+, that expressed and secreted M-CSF was identified. Another clonal cell line, designated N+/CSF-, did not secrete M-CSF at levels detectable by ELISA. B16F10, N+/CSF-, and N+/CSF+ cells, individually or in combination, were injected intravenously or subcutaneously into C57BL/6 mice; we then evaluated the tumorigenicity and metastatic behavior of the cells, as well as the immune responses and survival of the mice. The immune responses assayed were the cytotoxic T lymphocyte (CTL) and peritoneal exudate cell (PEC) tumoricidal activities. RESULTS: Injection of B16F10 cells into the tail vein of C57BL/6 mice led to the establishment of lung metastases by week 2 and death by week 8. Injection of the N+/CSF+ or N+/CSF- cells led to the establishment of lung metastases that were detected at 2 and 3 weeks, respectively; however, these metastatic lesions were eliminated, and the animals had survival rates similar to those of the noninjected control mice. Injection of mice with a mixture of B16F10 and N+/CSF- cells resulted in the development of metastatic disease and 0% survival at 8 weeks, whereas mice that had been given an injection of a mixture of B16F10 and N+/CSF+ cells had an 80% survival rate at 8 weeks and survived at least two times longer (P = .007). The CTL and PEC tumoricidal activities in animals given an injection of N+/CSF+ cells suggested that monocytes and lymphocytes were responsible for the observed antitumor response. CONCLUSION: These findings suggest that the expression of M CSF by genetically modified melanoma cells caused an effective antitumor immune response in host C57BL/6 mice and, thus, prolonged survival over that observed in the control mice. PMID- 7791231 TI - Lung cancer in radon-exposed miners and estimation of risk from indoor exposure. AB - BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners. PMID- 7791233 TI - Mutagens from heated Chinese and U.S. cooking oils. AB - BACKGROUND: The lung cancer incidence in Chinese women is among the highest in the world, but tobacco smoking accounts for only a minority of the cancers. Epidemiologic investigations of lung cancer among Chinese women have implicated exposure to indoor air pollution from wok cooking, where the volatile emissions from unrefined cooking oils are mutagenic. PURPOSE: This study was conducted to identify and quantify the potentially mutagenic substances emitted from a variety of cooking oils heated to the temperatures typically used in wok cooking. METHODS: Several cooking oils and fatty acids were heated in a wok to boiling, at temperatures (for the cooking oils) that ranged from 240 degrees C to 280 degrees C (typical cooking temperatures in Shanghai, China). The oils tested were unrefined Chinese rapeseed, refined U.S. rapeseed (known as canola), Chinese soybean, and Chinese peanut in addition to linolenic, linoleic, and erucic fatty acids. Condensates of the emissions were collected and tested in the Salmonella mutation assay (using Salmonella typhimurium tester strains TA98 and TA104). Volatile decomposition products also were subjected to gas chromatography and mass spectroscopy. Aldehydes were detected using high-performance liquid chromatography and UV spectroscopy. RESULTS: 1,3-Butadiene, benzene, acrolein, formaldehyde, and other related compounds were qualitatively and quantitatively detected, with emissions tending to be highest for unrefined Chinese rapeseed oil and lowest for peanut oil. The emission of 1,3-butadiene and benzene was approximately 22-fold and 12-fold higher, respectively, from heated unrefined Chinese rapeseed oil than from heated peanut oil. Lowering the cooking temperatures or adding an antioxidant, such as butylated hydroxyanisole, before cooking decreased the amount of these volatile emissions. Among the individual fatty acids tested, heated linolenic acid produced the greatest quantities of 1,3 butadiene, benzene, and acrolein. Separately, the mutagenicity of individual volatile emission condensates was correlated with linolenic acid content (r = .83; P = .0004). Condensates from heated linolenic acid, but not linoleic or erucic acid, were highly mutagenic. CONCLUSIONS: These studies, combined with experimental and epidemiologic findings, suggest that high-temperature wok cooking with unrefined Chinese rapeseed oil may increase lung cancer risk. This study indicates methods that may reduce that risk. IMPLICATIONS: The common use of wok cooking in China might be an important but controllable risk factor in the etiology of lung cancer. In the United States, where cooking oils are usually refined for purity, additional studies should be conducted to further quantify the potential risks of such methods of cooking. PMID- 7791232 TI - Oral contraceptives and breast cancer risk among younger women. AB - BACKGROUND: Several studies have suggested a link between oral contraceptive use and breast cancer in younger women, but it is possible that chance or bias, including selective screening of contraceptive users, contributed to the putative association. PURPOSE: Given that oral contraceptives were first marketed in the United States in the early 1960s, we conducted a population-based case-control study to examine the relationship between use of oral contraceptives and breast cancer among women in a recently assembled cohort, focusing on women younger than 45 years of age who had the opportunity for exposure throughout their entire reproductive years. METHODS: Breast cancer patients and healthy control subjects were identified, the latter group by random-digit dialing, in Atlanta, Ga., Seattle/Puget Sound, Wash., and central New Jersey. In Seattle and New Jersey, the study was confined to women 20 through 44 years of age; in Atlanta the age range was extended through 54 years. Patients included women with in situ or invasive breast cancer newly diagnosed during the period of May 1, 1990, through December 31, 1992. In-person interviews were completed by 2203 (86.4%) of 2551 eligible patients and 2009 (78.1%) of 2571 eligible control subjects. Analyses focused on women younger than 45 years of age (1648 patients and 1505 control subjects) to maximize opportunities for extended exposure. Logistic regression analyses were used to obtain maximum likelihood estimates of relative risks (RRs) and their 95% confidence intervals (CIs). RESULTS: Among women younger than 45 years, oral contraceptive use for 6 months or longer was associated with an RR for breast cancer of 1.3 (95% CI = 1.1-1.5). Risks were enhanced for breast cancers occurring prior to age 35 years (RR = 1.7; 95% CI = 1.2-2.6), with the RR rising to 2.2 (95% CI = 1.2-4.1) for users of 10 or more years. The RR for breast cancer for those whose oral contraceptive use began early (before age 18 years) and continued long-term (> 10 years) was even higher (RR = 3.1; 95% CI = 1.4 6.7). The RRs observed for those who used oral contraceptives within 5 years of cancer diagnosis were higher than for those who had not, with the effect most marked for women younger than age 35 years (RR = 2.0; 95% CI = 1.3-3.1). Oral contraceptive associations were also strongest for cancers diagnosed at advanced stages. Evaluation of screening histories and methods of diagnosis failed to support the speculation that associations could be due to selective screening. Among women 45 years of age and older, no associations of risk with use of oral contraceptives were noted. CONCLUSIONS: The relationship between oral contraceptives and breast cancer in young women appears to have a biologic basis rather than to be an artifact or the result of bias. PMID- 7791234 TI - Chemoprevention of rat prostate carcinogenesis by use of finasteride or casodex. PMID- 7791235 TI - Re: Circumvention of multi-drug resistance with anti-P-glycoprotein antibodies: clinical potential or experimental artifact? PMID- 7791236 TI - Human gamma delta T lymphocytes use N-CAM to interact with the subendothelial matrix. PMID- 7791237 TI - Re: Adenocarcinoma of the esophagus: role of obesity and diet. PMID- 7791238 TI - First complex disasters symposium features dramatically timely topics. PMID- 7791239 TI - Will US polio immunization rely on IPV or OPV? PMID- 7791240 TI - From the Institute of Medicine. PMID- 7791241 TI - From the Centers for Disease Control and Prevention. Unexplained illness among Persian Gulf War veterans in an Air National Guard Unit: preliminary report- August 1990-March 1995. PMID- 7791242 TI - From the Centers for Disease Control and Prevention. Enhanced detection of sporadic Escherichia coli O157:H7 infections--New Jersey, July 1994. PMID- 7791243 TI - From the Centers for Disease Control and Prevention. Escherichia coli O157:H7 outbreak at a summer camp--Virginia, 1994. PMID- 7791244 TI - From the Centers for Disease Control and Prevention. Deaths from melanoma--United States, 1973-1992. PMID- 7791245 TI - Malpractice, patient satisfaction, and physician-patient communication. PMID- 7791246 TI - Malpractice, patient satisfaction, and physician-patient communication. PMID- 7791247 TI - Suitability of fetal tissue for transplantation. PMID- 7791248 TI - Hypertension in the elderly: correction and clarification. PMID- 7791249 TI - Hypertension in the elderly: correction and clarification. PMID- 7791250 TI - Treatment of acute cystitis. PMID- 7791251 TI - Treatment of acute cystitis. PMID- 7791252 TI - Maternal growth during adolescent pregnancy. PMID- 7791253 TI - The cost of topical drugs for dermatophyte infections. PMID- 7791254 TI - The cost of topical drugs for dermatophyte infections. PMID- 7791255 TI - Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. AB - OBJECTIVES: To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies. DESIGN: Prospective cohort study. PARTICIPANTS: All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units. MAIN OUTCOME MEASURES: Adverse drug events and potential ADEs. METHODS: Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability. RESULTS: Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threatening, 30% serious, and 57% significant. Twenty eight percent were judged preventable. Of the life-threatening and serious ADEs, 42% were preventable, compared with 18% of significant ADEs. Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage. CONCLUSION: Adverse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process. PMID- 7791256 TI - Systems analysis of adverse drug events. ADE Prevention Study Group. AB - OBJECTIVE: To identify and evaluate the systems failures that underlie errors causing adverse drug events (ADEs) and potential ADEs. DESIGN: Systems analysis of events from a prospective cohort study. PARTICIPANTS: All admissions to 11 medical and surgical units in two tertiary care hospitals over a 6-month period. MAIN OUTCOME MEASURES: Errors, proximal causes, and systems failures. METHODS: Errors were detected by interviews of those involved. Errors were classified according to proximal cause and underlying systems failure by multidisciplinary teams of physicians, nurses, pharmacists, and systems analysts. RESULTS: During this period, 334 errors were detected as the causes of 264 preventable ADEs and potential ADEs. Sixteen major systems failures were identified as the underlying causes of the errors. The most common systems failure was in the dissemination of drug knowledge, particularly to physicians, accounting for 29% of the 334 errors. Inadequate availability of patient information, such as the results of laboratory tests, was associated with 18% of errors. Seven systems failures accounted for 78% of the errors; all could be improved by better information systems. CONCLUSIONS: Hospital personnel willingly participated in the detection and investigation of drug use errors and were able to identify underlying systems failures. The most common defects were in systems to disseminate knowledge about drugs and to make drug and patient information readily accessible at the time it is needed. Systems changes to improve dissemination and display of drug and patient data should make errors in the use of drugs less likely. PMID- 7791258 TI - A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome. AB - OBJECTIVE: To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. DESIGN: Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. SETTING: University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. SUBJECTS: Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. INTERVENTION: A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. MAIN OUTCOME MEASURES: Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. RESULTS: Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. CONCLUSIONS: Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS. PMID- 7791257 TI - Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. AB - OBJECTIVE: To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults. DESIGN: Randomized controlled clinical trial. SETTING: Orthopedic specialty academic hospital. PATIENTS: A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years; 70% women. INTERVENTION: Random assignment to either epidural or general anesthesia. MAIN OUTCOME MEASURES: A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively. Cognitive outcome was assessed by within-patient change on 10 tests of memory, psychomotor, and language skills. Prospective standardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes. RESULTS: The two groups were similar at baseline in terms of age, sex, comorbidity, and cognitive function. There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months. Overall, 5% of patients showed a long-term clinically significant deterioration in cognitive function. There was no difference between the anesthesia groups in the incidence of major cardiovascular complications (3% overall). CONCLUSIONS: The type of anesthesia, general or epidural, does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement. This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date, with more than 99% power to detect a clinically significant difference on any of the neuropsychological tests. PMID- 7791259 TI - A piece of my mind. Middle man in the prostate puzzle. PMID- 7791260 TI - Pitfalls in the diagnosis and treatment of Lyme disease in children. AB - OBJECTIVE: To define pitfalls of diagnosis and treatment of Lyme disease in children. DESIGN: Case series. SETTING: A university Lyme disease clinic in a Lyme disease endemic area. PATIENTS: A total of 146 pediatric patients (mean age, 9.9 years) referred with possible Lyme disease. MAIN OUTCOME MEASURES: Of the 146 patients, 56 (38%) were overdiagnosed, 12 (8%) were underdiagnosed, and 75 (51%) were correctly diagnosed with Lyme disease. Treatment errors were made for 19 (25%) of these 75 patients. In addition, three patients (2%) with tick bites were misdiagnosed or mistreated. Frequent pitfalls included misidentifying rashes as erythema migrans, ascribing nonspecific symptoms to Lyme disease, failing to ascribe fleeting objective symptoms to Lyme disease, and inappropriate antibiotic therapy for patients with Lyme disease. CONCLUSIONS: Errors in the diagnosis and treatment of Lyme disease in children are common. PMID- 7791261 TI - A 72-year-old man with localized prostate cancer. PMID- 7791262 TI - Above all 'do no harm'. How shall we avoid errors in medicine? PMID- 7791263 TI - Clinical crossroads: an invitation. PMID- 7791264 TI - The reconfiguration of US medicine. PMID- 7791265 TI - [Comparison of complement activation between tuberculous and malignant pleuritis]. AB - Complement activation products in pleural effusions were studied to clarify the causes of tuberculous and malignant pleuritis. Pleural SC5b-9, an activation product of complement common pathway, was significantly higher in tuberculous effusions than in malignant ones. In the tuberculous effusions, the levels of SC5b-9 and LDH (a marker of tissue damage) were significantly correlated, but in the malignant effusions these two values were not correlated. In the tuberculous effusions, SC5b-9 and Bb values were significantly correlated, but SC5b-9 and C4d were not, and nor were SC5b-9 and immune complex. In the malignant effusions, SC5b-9 and Bb values were low and were not significantly correlated. These results suggest that complement activation plays a significant role in tuberculous pleuritis, but not in malignant pleuritis. PMID- 7791266 TI - [Clinical study of radiation pneumonitis over 10 years]. AB - We studied clinical aspects of radiation pneumonitis from 1983 to 1992. Fifty seven patients admitted to our hospital because of lung cancer were treated with radiotherapy, and radiation pneumonitis developed in 20 (35.1%). The incidence of radiation pneumonitis was closely related to male sex, chronic obstructive lung disease, and chemotherapy. Pneumonitis was not related to age, or to the area or amount of radiation. Eighteen cases (90%) of pneumonitis occurred during or within one month after radiotherapy. In all but five cases (25%), pneumonitis was limited to the area of radiation. Treatment was mainly with steroids. In 4 cases (20%), pneumonitis recurred when steroid therapy was reduced, and five patients (10%) died. PMID- 7791267 TI - [Effect of supplementation with eicosapentaenoic acid ethyl ester, MND-21, on generation of leukotrienes by calcium ionophore-activated leukocytes in bronchial asthma]. AB - The effects of dietary supplementation with highly purified eicosapentaenoic acid ethyl ester (EPA-E) (MND-21) on asthma symptoms, fatty acids in serum, and generation of leukotriene (LT) C4, LTC5, LTB4 and LTB5 by leukocytes stimulated with calcium ionophore A23187 were studied in 10 patients with bronchial asthma. The patients received nine capsules of MND-21 (2.7 g EPA-E) each day for 12 weeks. Leukocytes obtained from 39 patients with asthma who did not receive EPA-E were used as the control. Fatty acid composition was evaluated by gas chromatography and LT generation was measured by reverse-phase high performance liquid chromatography. EPA-E increased EPA content more than threefold, without changing the quantities of arachidonic acid in serum lipids. Leukocytes obtained from patients given EPA-E for 4 weeks generated less LTC4 (53.5 +/- 23.3 ng/10(7) cells) and LTB4 (24.9 +/- 12.4 ng/10(7) cells) than did those from control patients (142.4 +/- 91.6 ng/10(7) cells and 58.3 +/- 34.8 ng/10(7) cells, respectively). Although significant levels of LTC5 and LTB5 were present after 4 weeks of EPA-E (6.5 +/- 1.9 ng/10(7) cells and 4.6 +/- 2.7 ng/10(7) cells, respectively), generation of total LTC (LTC4 + LTC5) and total LTB (LTB4 + LTB5) were substantially suppressed. Symptoms had improved after two months of EPA-E, but the effect was temporary. We conclude that in patients with asthma, treatment with EPA-E may attenuate leukocyte function without distinctly changing the severity of asthma. PMID- 7791268 TI - [Infiltration of cells in the bronchial mucosa in atopic and non-atopic patients with bronchial asthma]. AB - Numbers of T lymphocytes, eosinophils, neutrophils, and mast cells in samples of bronchial mucosa were measured with monoclonal antibodies. Samples were obtained by biopsy from atopic (A) and non-atopic (NA) patients with bronchial asthma, and from healthy control subjects (C). The numbers of T lymphocytes, eosinophils, and neutrophils did not differ significantly between the A group and the NA group, but the A group had significantly more mast cells than the NA group (p < 0.025). The difference was greatest in the mucosal epithelium (p < 0.01). Electron microscopy revealed many degranulating mast cells in the A group. These results suggest that in atopic patients with bronchial asthma, mast cells infiltrate into bronchial mucosal epithelium and contribute to inflammation. PMID- 7791269 TI - [Efficacy of high-dose beclomethasone in patients with stable chronic obstructive pulmonary disease]. AB - To study the role of inhaled steroids in treating patients with chronic obstructive pulmonary disease (COPD), 1.6 mg of beclomethasone dipropionate (BDP) were given for 2 weeks after 0.5 mg/kg of oral prednisolone (PSL) for 2 weeks to 43 patients with COPD (mean age 68.7 +/- 5.2 years, mean baseline FEV1, 1.13 +/- 0.44 L). When responders to a corticosteroid (PSL or BDP) were defined as those with a post-steroid EFV1/baseline FEV1 > or = 115% and a post-steroid FEV1 baseline FEV1 > or = 0.2 L, 12 out of 43 patients responded to 30 mg of PSL for 2 weeks and 13 responded to 1.6 mg of BDP for 2 weeks. We considered those 17 patients who responded to 2 weeks of PSL or 2 weeks of BDP or both, to be possible steroid responders, and they continued inhaling BDP for 4 more weeks. In 8 of these 17 patients (19%), FEV1 had increased by the end of the 6 weeks. Inhaled BDP was considered useful in treating some patients with COPD. PMID- 7791270 TI - [Long-term study of patients with sequelae of pulmonary tuberculosis after pneumonectomy--obstructive impairment and its causes]. AB - Changes in pulmonary function, chest X-ray films, and CT were retrospectively studied in patients with sequeae of pulmonary tuberculosis 30 years after pneumonectomy (PNX). Over more than 10 years, VC and FEV1% changed at a rate of 23.2 +/- 8.8 ml and 0.683 +/- 0.688% per year, respectively. In the patients studied 30 years after PNX (N = 30), VC was 900 +/- 210 ml, %VC 31.6 +/- 8.1%, and FEV1% was 67.2 +/- 6.8%. About half of these patients had mild airway obstruction. FEV1% was negatively related to the distance from the hilum to the diaphragm on the mid-clavicular line (on the chest films) divided by body height (r = -0.607). Therefore, we think that the airway obstruction may be due to overextension of the bronchi of middle and lower lobes. Emphysema was not found in 18 patients who had no sign of hyperinflation or herniation of the remaining lung to the PNX side on their CT, but it was found in one patient with these signs. PMID- 7791271 TI - [A case of eosinophilic pneumonia presenting as hemoptysis, with epithelioid cell granuloma on lung biopsy]. AB - A 60-year-old woman was admitted because of hemoptysis and dyspnea on exertion, which began one month before admission and gradually increased. Chest X-ray film taken on admission showed an infiltrative shadow in and around the left posterior basal segment. Chest CT disclosed peripheral and patchy consolidation with some air bronchograms and interstitial thickening in the left basal segments. Bronchoalveolar lavage fluid contained many red blood cells and abnormally high numbers of eosinophils and lymphocytes. The specimen obtained by CT-guided lung biopsy revealed epithelioid cell granulomas, hemosiderin-laden macrophages, diffuse infiltration of small round cells with a few eosinophils and monocytes in the alveolar septa, and many eosinophils in the intraalveolar exudates. No pathogens of pulmonary eosinophilia were identified and there was no secondary pulmonary eosinophilia. Therefore, we diagnosed eosinophilic pneumonia with no obvious cause. Hemoptysis may have been due to alveolar hemorrhage of eosinophilic pneumonia. The hemoptysis and chest infiltrative shadow disappeared rapidly after the start of treatment with oral prednisolone. PMID- 7791272 TI - [A case of chronic hypersensitivity pneumonitis due to long term exposure to toluene diisocyanate]. AB - A 55-year-old paint sprayer, who had been working with paint containing toluence diisocyanate since age 20, was admitted to our hospital with a complaint of exertional dyspnea. Physical examination revealed clubbed fingers, and fine crackles were audible in both lower lung fields. The thoracic CT film showed diffuse linear and ringed shadows in both lung fields. Open lung biopsy disclosed alveolitis and fibrosis as well as infiltration of mononuclear cells, but no Masson bodies or granulomas. Toluene diisocyanate-specific antibody was positive. Based on these results, we diagnosed chronic hypersensitivity pneumonitis due to the chemical. To our knowledge, there has been no previously reported case of chronic hypersensitivity pneumonitis due to isocyanate. PMID- 7791273 TI - [A case of sarcoidosis discovered by onset of pneumothorax]. AB - A 24-year-old man was admitted to our hospital with left back and chest pain. A chest X-ray film showed left pneumothorax, bilateral hilar lymphadenopathy, mediastinal widening, and multiple nodular shadows in both lung fields. Chest CT showed a large nodule just under the pleura. High serum ACE and lyzozyme levels, and a noncaseating epithelioid granuloma (revealed by TBLB) led to the diagnosis of sarcoidosis. Steroid therapy was started to prevent a cardiac lesion. Pneumothorax secondary to sarcoidosis in its early stage is rare, and in this case the pneumothorax may have been caused by rupture into pleural space of the largest nodule in the left S9, as a result of necrosis. PMID- 7791274 TI - [Idiopathic interstitial pneumonia (type B) with subacute progressively enlarged bullae]. AB - A 70-year-old man with a 10-year history of seal engraving presented with exertional dyspnea and dry coughing. Chest roentgenograms showed an interstitial shadow and bilateral progressively enlarging bullae. Open lung biopsy led to the diagnosis of idiopathic interstitial pneumonia (Type B). The size of bullae usually does not change, so cases such as this are rare because the bullae continued to expand subacutely. Persistent stimulation by the inhaled A1 and Si may have played a role in the pathogenesis of this condition. PMID- 7791276 TI - [A case of tropical eosinophilia associated with pleural effusion]. AB - A 52-year-old man was admitted to Keio University Hospital for determination of the etiology of a bilateral pleural effusion associated with marked eosinophilia (10200 cells/mm3). He had been in Vietnam for three years and had returned to Japan in May 1993. He was suffering from tropical eosinophilia, as clearly indicated by eosinophilia, elevation of serum IgE level (708 IU/ml), the presence of anti-dirofilarial antibodies, and the absence of microfilaria in the blood. The pleural effusion was an exudate and 51% of the cells in the effusion were eosinophils. In the effusion, no parasites were detected but anti-dirofilarial antibodies were found (the titer was as high as that in the serum). Diethylcarbamazine was given, and a steroid had to be superimposed because of wheezing. These treatments successfully reduced the bronchoconstriction, eosinophilia and accumulation of pleural effusion. Tropical eosinophilia has generally been thought not to be associated with pleural effusion. This is only the third case report of tropical eosinophilia with authentic pleural effusion. PMID- 7791275 TI - [A case of extramedullary plasmacytoma of the lung associated with nodular deposit of amyloid]. AB - A 63-year-old man underwent left upper lobectomy because of a 35-mm tumor in the lingula. Microscopic findings showed that the tumor was composed of a proliferation of plasma cells, and that in some areas eosinophilic amorphous material had been deposited between the tumor cells. By immunoperoxidase staining, the tumor cells were positive for IgG and kappa chain, but they were negative for lambda chain. In addition to the tumor in the lingula, another nodule was found in the left lower lobe and was resected at thoracotomy. The nodule was composed of diffuse eosinophilic amorphous material, which was found to be amyloid after Congo red staining and observation in polarized light. In and around the nodule, a few plasma cells were noted and these cells were also positive for IgG and kappa chain, but negative for lambda chain immunoperoxidase staining. In serum taken from the patient before surgery, M-protein was not detected by immuno electrophoresis but polyclonal hypergammaglobulinemia was noted, and it continued after the thoractomy. Bone marrow examination and a bone scintigram revealed no abnormality. In this case, a pulmonary plasmacytma co existed with nodular pulmonary amyloidosis. We could not determine which lesion developed first, but the results of the immunoperoxidase staining of plasma cells in both lesions indicate that the origin of the plasmacytoma was probably the same as that of the nodular amyloid. PMID- 7791277 TI - [A case of small cell lung cancer that developed during therapy for myasthenia gravis]. AB - A 56-year-old man had been complaining of progressive proximal muscle weakness and bilateral ptosis before his first admission to our hospital. He received an injection of edrophonium chloride, which resulted in remarkable improvement of muscle strength. Electromyographic studies revealed a compound muscle action potential that decreased after repetitive stimulation at a high rate (15 Hz). He was regarded as having myasthenia gravis (MG) rather than Eaton-Lambert syndrome because of these findings. Eighteen months after successful treatment of MG with oral anticholinesterase medication, he complained of an abdominal mass. The mass was found to be a tumor that had metastasized from a primary small cell carcinoma of the lung. Cases of MG with small cell carcinoma of the lung seem to be very rare, and the details of the relationship between them remain unknown. In this patient, MG may have developed by paraneoplastic mechanisms. This hypothesis is interesting, since it has been demonstrated recently by molecular biological techniques that small cell carcinomas of the lung express nicotinic acetylcholine receptors. PMID- 7791278 TI - [A case of necrotizing sarcoid granulomatosis diagnosed by open lung biopsy]. AB - A 59-year-old man had an abnormal shadow on chest X-ray film. He was admitted to Tohoku-chuou Hospital, and a lung lesion in the right lower lobe was diagnosed as a benign nodule. A new nodular lesion appeared on a chest X-ray film taken two months after his discharge from the hospital. Both lesions were in the same lobe; the older one was in segment 9 and the newer one was in segment 10. For the lesion in segment 10, malignancy was not ruled out, so open lung biopsy (right lower lobectomy) was done. With the findings of angitis and focal necrosis surrounded by granulomas consisting of epthelioid cells and multinuclear giant cells, the new lesion in segment 10 was diagnosed as necrotizing sarcoid granulomatosis. The older lesion in segment 9 was a tuberculoma. We conclude that in this case the open lung biopsy was necessary to diagnose necrotizing sarcoid granulomatosis in lung. PMID- 7791280 TI - [A case of productive aspergilloma on the inner wall of a cavity, in which perbronchial fiberoptic bronchoscopy within the cavity was useful for the diagnosis and therapeutic evaluation]. AB - A 45-year-old man complaining of bloody sputum was admitted. He had been treated for pulmonary tuberculosis since October 1988. He had bloody sputum in October 1989. His chest X-ray findings showed a cavitary lesion with a thickened and irregular wall in the right upper lobe. Fiberoptic bronchoscopy revealed white nodules on the cavity wall and the biopsy specimen from the nodule yielded a fungus granuloma. Aspergillus fumigatus was cultured from the sputum obtained after the bronchoscopy. Based on these findings, endobronchial aspergillosis and productive aspergilloma on the inner wall of a cavity was diagnosed. He was treated with oral anti-fungal drugs for 4 years. On chest X-ray films taken in June 1993, the cavity had enlarged, and the thickening and irregularity of the cavity wall had disappeared. Transbronchial fiberoptic bronchoscopy within the cavity showed whitish nodules and the cytology specimen obtained from the nodules by brushing yielded fungi, he was treated with oral itraconazol. Six months later, re-examination of the cavity revealed that the wall had become thinner and that the nodules on the inner wall had disappeared. This case illustrates the importance of bronchoscopy, in the diagnosis and evaluation of treatment of productive aspergilloma on the inner wall of a cavity. PMID- 7791282 TI - [Visual field compendium. Interpretation of perimetry findings. Comprehensive diagnostic measures]. PMID- 7791281 TI - [A case of intra-pulmonary lymph nodes presenting as multiple small nodular lesions in both lungs]. AB - A 59-year-old man came to our hospital for further examination of multiple small nodular lesions in both lungs. Chest CT scan revealed multiple nodular lesions in rt-S6, It-S5, and It-S9 (two lesions). All of these nodules measured about 10 mm or less and those in It-S9 had spicula. Bronchoscopic examination did not yield a definitive diagnosis, so open lung biopsy was done. The open lung biopsy specimen revealed intra-pulmonary lymph nodes with anthracosis and pulmonary emphysema. Intrapulmonary lymph nodes are very difficult to distinguish from small lung tumors by radiographic examination alone, so the possibility that small nodules in the lungs may be intra-pulmonary lymph nodes should be kept in mind. PMID- 7791279 TI - [Legionella pneumonia diagnosed by urinary antigen detection]. AB - A 63-year-old man with dyspnea and high fever was admitted to the hospital. A pneumonic shadow in the right lower lung field was observed. After administration of rifampicin and clarithromycin, his symptoms were gradually alleviated. Although Legionella pneumonia was highly suspected, Legionella pneumophila was not isolated from his sputum specimens and the serum level of indirect immunofluorescent antibody titer was not significantly elevated. However, we believe it is very likely that he had Legionella pneumonia, because we detected a high density of urinary Legionella pneumophila serogroup 1 antigen by antigen capture EIA. PMID- 7791283 TI - [Vitrectomy in proliferative vitreoretinopathy. Anatomical and functional results in 501 patients]. AB - BACKGROUND: Modern vitreoretinal surgery allows a successful management of most cases of retinal detachment (RD) due to proliferative vitreoretinopathy (PVR). Failure of a vitrectomy in these cases is generally caused by a recurrence of PVR. Little is known about the postoperative 'life cycle' of proliferative cellular processes within the periretinal space. An adequate retreatment of PVR recurrences may improve the anatomical and functional results of a vitrectomy. MATERIAL AND METHODS: The retrospective study comprises 501 consecutive eyes operated for non-diabetic traction RD. Conventional retinal surgery preceded the vitrectomy in 36% of the cases. PVR was staged according to the classification of the Retina Society (14) with supplemental stages for 'anterior loop' formation, epimacular and subretinal membranes. The mean follow up of 139 eyes with one single vitrectomy was 24.2 months. The time-course of recurrent PVR in 362 eyes (72%, mean follow-up 34.2 months) was analyzed. Silicone-oil tamponade was used in 343 (69%) eyes. RESULTS: Recurrent PVR occurred predominantly within 1 to 9 months (median 1.8 mos) after vitrectomy. Latencies of recurrences did not differ significantly between PVR-C and D stages. Reattachment of the retina was achieved in about 85% of PVR-C and 70% of PVR-D stages. Anatomical results were better in non-traumatic RD cases. Final visual acuity of eyes operated since 1990 was 5/200 or better in 78% C-stages and 65% D-stages (follow-up of > or = 12 months). The final visual acuity was 20/100 or better in 33% of all PVR-C cases and 9.5% of all PVR-D cases. Significantly improved visual results were achieved in eyes operated with silicone oil tamponade, and in the later series of 279 eyes operated since 1990. The rate of postoperative total blindness was reduced from 16.7% before 1990 to 3.6% after 1990. CONCLUSION: Blindness due to traction RD can be avoided by vitreoretinal surgery in about 75% of PVR-C and over 50% of PVR D cases provided that PVR recurrences are detected early and treated adequately. PMID- 7791284 TI - [Early vitrectomy in endogenous juvenile uveitis intermedia--a long-term study]. AB - BACKGROUND: The intermediate uveitis is one of the most common intraocular manifestations of inflammation during infancy and adolescence. The success of intensive pharmacological treatment is rather limited and often associated with heavy side effects. PATIENTS AND METHODS: In 25 eyes with juvenile uveitis intermedia (age of the patients between 5 and 18 years, mean 13.5 years) and visual acuities between 0.02 and 0.4 (mean 0.19) an early vitrectomy was performed after failure of conservative treatment and peripheral cryocoagulation. RESULTS: Almost all patients (22 out of 25) showed an improvement of visual acuity within the first 6 months of the surgery. Among the patients with a remarkable improvement of visual acuity 7 eyes had a chronic cystoid macular oedema which showed a regression postoperatively. Additionally, the number and the course of inflammatory periods could be reduced postoperatively. An increase of preexisting lens opacities, however, has not been noticed even after a follow up period of 10 years. CONCLUSIONS: The results show that an early vitrectomy in cases of juvenile uveitis intermedia often leads to a stabilization or an improvement of visual acuity and a regression of the inflammatory attacks (episodes). Therefore, in children and adolescents with endogenous uveitis intermedia a pars plana vitrectomy instead of a long-term systemic immunosuppression associated with heavy side-effects should be considered. PMID- 7791285 TI - [Phototherapeutic keratectomy as the primary option before perforating keratoplasty]. AB - BACKGROUND: Argon fluoride excimer laser (193-nm) can perform precise corneal ablation with submicron accuracy and minimal reaction to the adjacent tissue. A possible application is anterior lamellar keratectomy to remove superficial corneal opacities and to smooth corneal irregularities. PATIENTS AND METHODS: Between August 1993 and June 1994 we performed a phototherapeutic keratectomy (PTK) in 35 patients with different corneal diseases by excimer laser (Aesculap Meditec). 3 cases (2 corneal dystrophies and 1 patient with a traumatic corneal opacity after chemical burn) are described more exactly with operative methods and postoperative results. RESULTS: By slitlamp microscopy we observed an improvement of the primary corneal disorder in all cases. Changing of refraction (hyperopic shift and newly formed astigmatism) arose in 2 out of 3 patients. CONCLUSIONS: Phototherapeutic keratectomy by excimer laser represents a secure, less invasive alternative to surgical methods promising quicker visual recovery. Often a penetrating keratoplasty can be avoided or delayed. PMID- 7791286 TI - [A new site-independent tonometer (ProTon) in comparison with the Goldmann applanation tonometer]. AB - BACKGROUND: A new position-independent and portable Mackay-Marg-tonometer in miniature, the so-called ProTon (PT), was compared with reference to its clinical usefulness with the Goldmann applanation tonometer (GAT), being a commonly accepted reference. METHODS: The intraocular pressure (IOP) in 164 eyes of 85 adults (patients and volunteers without ocular disease) was measured using the sequence GAT, PT and again GAT--each three times in a row-by three different investigators in a randomized scheme. In an attempt to detect any systemic influence, the difference obtained by subtracting the value measured using PT from the value attained using GAT was compared to the central corneal thickness and radius. Moreover, the central IOP readings were compared with the peripheral IOP in 60 eyes of 30 volunteers measured by PT, to detect any possible influence of the locality of measurement. Dependence of measurement on individual influences was examined by comparing PT-values obtained by each investigator. RESULTS: Linear regression analysis between PT (y-axis) and GAT (x-axis) for an IOP range of 0 to 62 mm Hg resulted in the following equation: PT = 1.036 x GAT 2.00 with a PT value standard deviation of 1.65 mm Hg (r = 0.988; p < 0.0001). Reproducibility of each of the three PT-values (mean pair difference of 1.1 mm Hg) corresponded to the analogous first two GAT-values (differences 1.0 up to 1.2 mm Hg). The mean IOP-value of 1) the GAT measurements (1 to 3) was 18.35 mm Hg, 2) of the last three GAT measurements, 17.15 mm Hg and 3) of all PT-measurements, 16.40 mm Hg. No statistical difference was found between the IOP measured centrally and peripherally. A clinically nonsignificant dependency for PT readings on the examiner was verified. CONCLUSION: Due to the high reproducibility, independency on examiner and acceptable correspondence of PT with GAT values, the PT appears to be a promising new development for use in measuring intraocular pressure. It will be necessary to modify the calibration of PT since IOP measured systematically about 2 mm Hg too low. PMID- 7791287 TI - [1H-NMR spectroscopic study of cysteamine eyedrops]. AB - BACKGROUND: The efficiency of cysteamine eye drops in the treatment of cystinosis has been demonstrated in several studies: Corneal cystine crystals can be removed by topical cysteamine. Cysteamie 0.5% eye drops were superior to a 0.1% solution. It is not clear how fast cysteamine is oxidized to cystamine under the influence of atmospheric oxygen. MATERIAL AND METHODS: Samples of a new bottled cysteamine 0.5% solution were analysed 1H-NMR-spectroscopically over a period of several weeks (AM 400/WB-NMR-instrument, Bruker/Karlsruhe; 400.15 MHz). Samples bottled in an argon atmosphere were compared to samples bottled without inert gas. Definite samples were opened four times a day (A). The remainder of the samples was stored closed (B). RESULTS: In sample A a 1:1 weight ratio between cysteamine and cystamine was reached after 38 days. In samples B cysteamine was not oxidized to cystamine. The initial amount of cystamine was something lower in samples with argon, but argon could not prevent the decrease of the cysteamine concentration in sample A. CONCLUSIONS: The preparation of cysteamine solution in an argon atmosphere is useful. One bottle can be used for about one week, if less than 10% of the oxidation product cystamine is accepted. PMID- 7791288 TI - [Traumatic wound dehiscence and corneal rupture 3 1/2 years after radial keratotomy]. AB - BACKGROUND: Severe complications such as a traumatic wound dehiscence have been described very rarely after radial keratotomy. The following case demonstrates for the first time that wound healing is not completed even 31/2 years postoperatively and that therefore an ocular blunt trauma may still cause a dehiscence of the radial incisions. CASE REPORT: A 22-year-old patient presented in July 1993 to our emergency unit because of a corneal perforation in his right eye after a blunt trauma. His past medical history was significant for radial keratotomy surgery performed in January 1990 to correct a bilateral low-degree myopia (OD = -3.25 D; OS = -3.75 D). At surgery a horizontal rupture running through the entire cornea and including the two radial keratotomies at the 3 and 9 o'clock position was evident. The whole iris and lens were missing. The retina was completely detached. The corneal laceration was sutured. Twelve days later the retina was reattached with an encircling band, vitrectomy, endolaser and cryocoagulation, as well as silicone oil fill. Finally, a penetrating keratoplasty was performed 6 months after the accident. Thereafter, visual acuity improved to 0.1. The histologic examination of the corneal button showed that the wound healing of the incisions that had remained intact was not completed yet. Epithelial plugs of various size were still filling the somewhat dehiscent wound margins. Fibroblastic activity was detected in the surrounding stroma. CONCLUSION: Even several years after surgery, blunt traumas represent a definite risk for eyes undergoing radial keratotomy. PMID- 7791289 TI - [Autosomal dominant keratoconus as the chief ocular symptom in Lobstein osteogenesis imperfecta tarda]. AB - BACKGROUND: Osteogenesis imperfecta is an autosomal inherited generalized disease of the soft tissue which can be divided into a congenital form (Vrolik) and a late-onset form named Lobstein. As the typical ocular symptom we find blue sclera whereas corneal changes as keratoconus are rarely documented. We report a family of 6 patients, all 5 examined being affected by keratoconus. PATIENTS AND METHODS: After a 14-year-period of wearing hard contact lenses due to a keratoconus a 26-year-old female patient developed a painful therapy-resistant keratitis (Acanthamoeba) which afforded a keratoplasty. A history of osteogenesis imperfecta tarda was known since childhood. Five further members in three generations of the family were certainly affected by osteogenesis imperfecta. We examined five patients with a computer-assisted corneal topography analysis system. RESULTS: Referring to localization and configuration of the keratoconus all of the five patients had a similar degree of affection. Only our patient revealed blue sclera. There was no correlation between the corneal curvature and the degree of affection of the bone. Both the keratoconus and the bone affections had shown no more progression after adolescence. CONCLUSION: With the use of computer-assisted corneal topography analysis we were able to show a keratoconus associated with osteogenesis imperfecta. The typical blue sclera was not found that often in this family. The shape of the keratoconus was similar in localization and configuration. Contrary to the normal progression of keratoconus in this family there was no more progression of refractive changes after adolescence. Association of keratoconus with osteogenesis imperfecta should be considered. Likewise in osteogenesis imperfecta the ophthalmologist should consider keratoconus beside blue sclera. PMID- 7791290 TI - [Clinical aspects of ataxia teleangiectatica (Louis-Bar syndrome)]. AB - BACKGROUND: Ataxia telangiectasia is an autosomal recessive inherited multisystem disease of childhood characterized by progressive cerebellar ataxia, oculo cutaneous telangiectasia, immunological defects with increased susceptibility to infection and malignant neoplasms. PATIENT: A 20-year-old patient with ataxia telangiectasia (Louis-Bar syndrome), demonstrating the typical features of this hereditary disease, is described. The ophthalmological findings showed telangiectasia of the horizontal conjunctival vessels in the exposed bulbar conjunctivae and oculomotor signs with pathological pursuit and command movements, dissociated nystagmus, failure of gaze holding and convergence. RESULTS: The ataxia is the first symptom and becomes apparent when the child starts to walk. The pathognomonic telangiectasia at the light-exposed areas of the bulbar conjunctiva point the way to the diagnosis. There is no specific treatment for this disease. CONCLUSIONS: The ophthalmologist is able to confirm the clinical diagnosis by demonstrating the telangiectasia. Due to the increased disposition to malignant neoplasms regular check-ups should be performed. PMID- 7791292 TI - [Toxic pulmonary edema]. PMID- 7791293 TI - [The selection of subjects for priority examination for the detection of ischemic heart disease]. PMID- 7791291 TI - [Tarantule hairs as corneal foreign bodies]. AB - A 22 year-old-man and owner of several tarantulas visited his ophthalmologist because of red itchy eyes. Additionally to kerato-conjunctivitis epidemica, uncommon hairs were found especially in his left cornea. Corrected visual acuity was 0.8. According to literature these spider hairs can induce granulomas in the meaning of ophthalmia nodosa, and even migrate inside the eye. Therefore we removed as many hairs as possible, but we left two, not to cause iatrogen perforation. The penetration depth was measured by laser tomography. Local steroids successfully prevented further granuloma formation. Regular ophthalmological controls are important to early detect possible changes, and if necessary to remove these hairs even from deeper corneal layers, in case by keratectomy. PMID- 7791294 TI - [A clinical assessment of ebrantil efficacy in arterial hypertension patients]. AB - From before treatment throughout its course a new hypotensive drug ebrantil was studied for clinical efficacy in 52 patients with essential, renal and thyrogenic arterial hypertension. Clinical instrumental and biochemical findings support the drug efficacy in management of a hypertensive crisis and sudden AF rise. The response was registered in 83.3% of the cases. A persistent hypotensive effect of 180 mg/day course ebrantil became obvious within the first week of the treatment, passing ahead of relevant changes in central hemodynamics and myocardial contractility. The drug acts by reducing both cardiac pre- and postload, the reduction being brought about due to diuretic effect. In response to AP decrease there was neither myocardial contractility depression nor reflex tachycardia. Psychoemotional testing confirmed the central effect of ebrantil promoting adaptation of patients to stress under long-term administration. The drug demonstrated good tolerance when used orally and intravenously. No bronchial pulmonary, carbohydrate and lipid metabolism, renal and hepatic function side effects were reported. 24-h AP monitoring proved ebrantil efficacy in essential and renal hypertension patients. PMID- 7791295 TI - [The effect of cardil (diltiazem) on thrombocyte aggregation in hypertension]. PMID- 7791296 TI - [The effect of kordaron on thyroid function in patients with ischemic heart disease]. AB - Thyroid function has been assessed in 56 patients with arrhythmic coronary heart disease (CHD) prior to and in the course of cordaron treatment. TTH level made up initially 1.39 +/- 0.27 IU/ml which was normal. T3 blood concentration was low- 1.28 +/- 0.06 nmol/l; T4 was normal--128.26 +/- 4.9 nmol/l. It is stated that CHD patients with arrhythmia develop latent hypothyrosis of T3-low-syndrome type. Arrhythmia treatment with cordaron aggravates T3 deficiency as the drug inhibits T4 conversion into T3 in peripheral tissues. It also causes toxic damage to thyroid parenchyma resulting in higher TH levels in the blood. CHD patients receiving long-term cordaron (1 to 8 years) have clinical picture of manifest hypothyrosis. Cordaron molecules includes iodine macro-doses, but these fail to initiate autoimmune thyroid process. PMID- 7791297 TI - [The hemodynamic, humoral and cellular effects of plasmapheresis in a refractory form of hypertension]. AB - Plasmapheresis effects on hemodynamics, neurohumoral, immunological and cell parameters were examined in 48 patients with refractory hypertension. Hypotensive effect of plasmapheresis was found to combine with positive hemodynamics and microcirculatory shifts, pressor factor activity inhibition, slowing of immunocomplex condition progress, reduced red cell deformability in refractory hypertension. PMID- 7791298 TI - [The involvement of the cardiovascular system in syphilis]. AB - Three lethal cases of visceral (cardiovascular) syphilis are reported. A pathogenetic role of specific vasculitis in organic lesions, of myocarditis in a decline of inotropic cardiac function and endarteritis of renal vessels in development of organic parenchymatous insufficiency are discussed. PMID- 7791299 TI - [Errors and difficulties in the diagnosis of malignant neoplasms in cardiology patients]. PMID- 7791301 TI - [The diagnostic significance of clinical signs of right ventricular insufficiency in patients with chronic obstructive bronchitis]. AB - An echocardiographic study of right ventricular myocardial contractility in 123 patients with chronic obstructive bronchitis (COB) confirmed the suggestion that in COB patients symptoms of right ventricular failure (cyanosis, acrocyanosis, crural edema, dilated liver) may have extracardiac origin. In echocardiographic diagnosis of right ventricular failure one should measure the speed of the anterior wall movements in the systole, diastole and ejection fraction. PMID- 7791303 TI - [The diagnostic significance of detecting L forms of Mycobacterium tuberculosis]. PMID- 7791304 TI - [The differential diagnostic potentials of the determination of adenosine deaminase in pleural exudate]. PMID- 7791305 TI - [The circadian phototherapy of bronchial asthma]. AB - The authors provide validation and technique of circadian phototherapy of bronchial asthma. Therapeutic effect of the method occurs because of correction of internal asynchronism, stimulation of endogenic synthesis of corticosteroids, antidepressive action. PMID- 7791302 TI - [Bronchial reactivity characteristics in EEG variants in bronchial asthma patients]. AB - The authors' investigations show that those asthmatics who have EEG-recorded lowered convulsion threshold of the cortical neurones exhibit higher hypersensitivity and hyperreactivity of the bronchi than those in patients with intact cortical-subcortical relationships. The interaction of the above parameters demonstrates stable relations between bronchial reactivity and bioelectrical cerebral activity. PMID- 7791300 TI - [The diagnosis of aspirin-induced asthma by using a functional model]. AB - The analysis of case history, clinical, laboratory and instrumental findings, objectively characterizing the patient's condition in two alternative groups (nonaspirin and aspirin bronchial asthma) enabled the authors to create a functional diagnostic model for aspirin bronchial asthma. The model-based computer program designed by the authors can perform early diagnosis of aspirin asthma outpatiently without any risk for the patients. PMID- 7791306 TI - [The mucolytic therapy of chronic obstructive bronchitis]. AB - The authors review the efficacy of mucolytic drugs in inhalations used alone and in combination with other substances (mucosolvin, ascoksal, powder soda, soda + ascoksal, soda + mucosolvin) against chronic obstructive bronchitis. The highest effect was achieved in inhalations of powder soda with ascoksal. This treatment is most potent in reducing the broncho-obstructive syndrome. PMID- 7791307 TI - [Electrostimulation of the diaphragmatic muscle in bronchial asthma patients]. AB - A study was made of the effect of transcutaneous diaphragmatic electrostimulation (2 mA, 0.3 ms, 20-30 V) on the external respiratory function in 12 asthmatic patients with respiratory insufficiency. The course comprised 7 daily sessions for 20 min. The improvement in respiratory function parameters was observed in the majority of the patients. The effect of electrostimulation was related to the quantity of the procedures. PMID- 7791309 TI - [The clinico-pathogenetic forms of hypertension (essential hypertension) and their differential treatment]. PMID- 7791310 TI - [Gastrotsepin in the therapy and prevention of peptic ulcer exacerbations associated with Helicobacter pylori bacteriosis]. PMID- 7791308 TI - [The correction of the imbalance in the proteinase-inhibitor system of patients with protracted pneumonia with the enterosorbent polifepan]. AB - The evidence obtained by the authors indicates that enterosorbent polyphepan corrects unbalance in the proteinase-inhibitory system of bronchial lavage from patients with lingering pneumonia and endobronchitis. Clinical symptoms improved also. A long-term (18 days) intermittent course (0.3 g/kg 4 days with 3-day intervals) is tolerated satisfactorily, produces no side effects (no colon dysfunction), retains normal hemoglobin values, total protein, enhances antiproteinase activity. As a result of the treatment hospital stay for the above patients reduced noticeably. PMID- 7791311 TI - [The rehabilitation of patients with venous diseases of the lower extremities under outpatient polyclinic conditions]. PMID- 7791312 TI - [Cases of tuberculous pericarditis]. PMID- 7791313 TI - [A rare case of alveolar echinococcosis of the lungs and liver complicated by a hepatopulmonary fistula]. PMID- 7791315 TI - [The control of student knowledge of internal diseases]. PMID- 7791316 TI - [The principles of the construction of a working classification of chronic pancreatitis]. PMID- 7791314 TI - [Generalized cryptococcosis]. PMID- 7791317 TI - [An evaluation of actovegin efficacy in bronchial asthma]. PMID- 7791318 TI - [The efficacy of hyperbaric oxygenation in resistant heart failure in elderly patients with ischemic heart disease]. PMID- 7791320 TI - [Bed bath, skin care, special genital care, dressings (invasive approaches)]. PMID- 7791321 TI - [Hysteroscopy--possibilities and limitations in diagnosis]. PMID- 7791319 TI - [Little-studied human viral hepatitides]. PMID- 7791323 TI - [Determination of personnel requirements in an intensive care unit]. PMID- 7791324 TI - [Cost reduction in the health care system. Example: wound care with hydrocolloid dressings]. PMID- 7791322 TI - [Hemofiltration, hemodiafiltration, biofiltration. Methods and indications in continuous kidney replacement techniques in an intensive care unit. 2]. PMID- 7791325 TI - [Truth--also at the bed side]. PMID- 7791326 TI - Sand, sandstorms, and sandcastles. PMID- 7791327 TI - Pulmonary thromboxane release following intestinal reperfusion. AB - Microvascular dysfunction is a prominent feature of the lung injury associated with intestinal reperfusion (IR). This study examines the hypothesis that IR induces pulmonary thromboxane A2 (TxA2) release, which contributes to pulmonary microvascular dysfunction. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR). Sham-operated animals served as controls (SHAM). Following IR or SHAM, the lungs were perfused in vitro with a modified Krebs buffer and ventilated with room air. Eicosanoid levels within the pulmonary venous effluent and bronchoalveolar lavage (BAL) fluid were determined (TxB2, 6 keto-PGF1a, and PGE2). Pulmonary artery pressure (PAP) was measured continuously and expressed as change from baseline in mm Hg. The dominant eicosanoid generated by the lungs in response to IR was TxB2. TxB2 levels in the pulmonary venous effluent of IR lungs were 75% greater than controls (P = 0.005). Similarly, TxB2 levels in the BAL were more than 2.5 times controls (P = 0.001). The change in PAP of lungs from IR animals was significantly greater than that of controls (4.1 +/- 1.5 vs 0.3 +/- 0.54 mm Hg, IR vs SHAM, P = 0.01). The increased PAP associated with IR lungs was prevented by cyclooxygenase inhibition with indomethacin (-1.28 +/- 0.29 mm Hg, P < 0.05) and thromboxane synthetase inhibition with imidazole (-1.75 +/- 0.95 mm Hg, P < 0.05). These experiments support the hypothesis that IR up-regulates endogenous pulmonary TxA2 release. Furthermore, the local release of TxA2 by the lung may contribute to the microvascular dysfunction characteristic of IR-induced lung injury. PMID- 7791328 TI - Splanchnic PGI2 release and "no reflow" following intestinal reperfusion. AB - This study examines the hypothesis that reduced splanchnic blood flow during intestinal reperfusion (IR) is associated with impaired release of the vasodilatory prostanoid PGI2. Sprague-Dawley rats underwent occlusion of the superior mesenteric artery (SMA) for 120 min and reperfusion for up to 60 min. SMA blood flow was measured by transonic flow probe and radiolabeled microspheres (141Ce and 103Ru). Sham-operated animals served as controls (SHAM). Splanchnic eicosanoid release was quantitated by measuring thromboxane B2 (TxB2, stable metabolite of TxA2), 6-keto-PGF1a (6-keto, stable metabolite of PGI2), and PGE2 within the portal vein (PV) and inferior vena cava (IVC) of animals sustaining IR and SHAM. SMA flow in IR animals was < 10% of baseline and 27% of SHAM when measured by transonic flow probe (8 +/- 2% and 29 +/- 3%, IR and SHAM, respectively, P < 0.05). Similar results were obtained when intestinal blood flow was measured with microspheres (0.33 +/- 0.12 vs 1.34 +/- 0.13 ml/min/g, IR vs SHAM, P < 0.05). The greatest change in IR-induced splanchnic eicosanoid release occurred with 6-keto. Following ischemia, 6-keto levels in the PV were twice those of SHAM (P < 0.05). Five minutes after reperfusion, PV 6-keto levels were 22 times those of controls (P < 0.05) and 4 times greater than those of the IVC (P < 0.05). By 60 min of reperfusion, levels of 6-keto were reduced to those in the IVC. These data support the hypothesis that splanchnic blood flow is critically reduced by severe IR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791329 TI - The effect of epidermal growth factor on mucosal function after ileal resection. AB - Since epidermal growth factor (EGF) enhances gut mucosal regeneration, the present study was undertaken to evaluate the effect of EGF on brush-border membrane enzyme activity and glutamine uptake in the intestinal remnant following extensive small bowel resection. Twenty-four adult male New Zealand White rabbits were divided into three groups: Group 1 (n = 12) served as controls. Groups 2 and 3 (n = 6 each) underwent a 50-60% mid-jejunoileal resection with anastomosis of the remaining intestine, leaving 90 cm between the pylorus and the ileocecal valve. Group 3 rabbits had a subcutaneous osmotic pump implanted to deliver EGF for 7 days at 0.3 micrograms/kg/hr. Rabbits from Groups 2 and 3 were sacrificed 3 weeks postoperation. Mucosa from the proximal and distal segments of the remaining intestine was analyzed for wet/dry weight, maltase and aminooligopeptidase activity, and glutamine uptake. There was a twofold increase in mucosal dry weight/cm of intestine in rabbits without EGF at 3 weeks (Group 2) and a fourfold increase in those given EGF (Group 3). The maltase enzyme capacity (UEnzyme/rabbit) increased from 37 +/- 10 in controls (Group 1) to 167 +/- 30 without EGF and 207 +/- 30 with EGF. The aminooligopeptidase enzyme capacity (UEnzyme/rabbit) increased from 55 +/- 10 to 147 +/- 20 and 226 +/- 30 in Groups 1, 2, and 3, respectively. Glutamine uptake capacity (microM glutamine/min) also increased significantly, from 63 +/- 19 in Group 1 to 88 +/- 6 without EGF and 162 +/- 18 with EGF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791330 TI - Nitric oxide inhibits LPS-induced IL-6 production in enterocytes. AB - In recent studies, production of interleukin-6 (IL-6) in cultured enterocytes was stimulated by lipolysaccharide (LPS). In other cell types, IL-6 production was inhibited by nitric oxide (NO). We tested the hypothesis that LPS-induced IL-6 production in the enterocyte is regulated, at least in part, by NO. IEC-6 cells (a rat intestinal epithelial cell line) were cultured for 3 days with different combinations of LPS (1-10 micrograms/ml), the NO synthase inhibitor N-omega-nitro L-arginine (NNA, 3-300 microM), L-arginine (10 mM), the NO donor sodium nitroprusside (SNP, 0.5-1 microM), or medium alone as control. IL-6 levels in the culture medium were determined by the B9 murine hybridoma bioassay. Nitrite, a stable end product of NO metabolism, was measured by HPLC. PCR was performed to determine inducible NO synthase (iNOS) mRNA expression in the IEC-6 cells. Treatment of IEC-6 cells with LPS stimulated IL-6 production. LPS-induced IL-6 production was further increased by NNA in a dose-dependent fashion. This effect of NNA was abolished by the addition of L-arginine. SNP caused a dose-dependent decrease in IL-6 production. Nitrite production was increased in a dose-dependent fashion after LPS treatment. PCR revealed an increase in iNOS mRNA expression in IEC-6 cells after administration of 1 microgram/ml LPS. The results suggest that NO inhibits LPS-induced IL-6 production in the enterocyte. NO may be an important regulator of intestinal cytokine response during sepsis and endotoxemia. PMID- 7791331 TI - Role of the vagal branches to the proximal stomach in mediating gastric distention-induced disruption of canine interdigestive upper gut motility. AB - Previous experiments from our laboratory have shown that the vagus nerves mediate proximal gastric distention-induced disruption of interdigestive motor patterns in the upper gut of dogs. Our aim was to determine the role of vagal innervation of the proximal stomach in mediating the response to nonnutrient proximal gastric distention. Five dogs underwent proximal gastric vagotomy (PGV) and placement of electrodes and manometry catheters on the antrum and the upper small intestine. Proximal gastric distention for 5 hr was achieved by inflating a thin, compliant bag in the proximal stomach. Four volumes of distention stimulus (0, 1.5, 12.5, and 25 ml/kg) were tested. As with total abdominal vagotomy, intragastric stimulus volumes of 12.5 and 25 ml/kg after PGV no longer inhibited cycling of the migrating motor complex in the stomach, duodenum, proximal jejunum, and distal jejunum. Volumes of 12.5 and 25 ml/kg did, however, on occasion, lead to the absence of phase III activity in the stomach or the duodenum when it would have been expected to precede phase III activity in the jejunum; this effect did not occur in the jejunum. These findings with a nonnutrient stimulus suggest that vagal branches to the proximal stomach might mediate, in part, the postprandial changes in upper gut motility in response to gastric distention by ingestion of a meal. PMID- 7791332 TI - Teleost fish islets: a potential source of endocrine tissue for the treatment of diabetes. AB - Anatomical separation of pancreatic islets in some teleost fish makes them a useful source of pancreatic endocrine tissue. Islets were harvested from tropical Tilapia fish (Oreochromis nilotica) and cultured for 24 hr at 37 degrees C. Eight athymic nude mice were rendered diabetic by streptozotocin (STZ) and transplanted under the kidney capsule with fish islets. After transplantation (Tx), nonfasting blood glucose (n-FBG), which was in all recipients > 450 mg/dl, decreased to < 100 mg/dl. At 4 and 7 weeks post-Tx, the intraperitoneal (ip) glucose tolerance test was performed in the normoglycemic Tx mice and in six normal controls. In controls, K value (percentage of decline in blood glucose/min) was 1.076 +/- 0.383 and in Tx mice it was 0.956 +/- 0.336 and 0.869 +/- 0.483 at 4 and 7 weeks, respectively (P = n.s.). Nephrectomy raised the n-FBG to pre-Tx levels. On immunohistochemistry, recipient's pancreata showed atrophic islets with no beta cell granules, while the islet-bearing kidneys had distinct beta-cells under their capsules. Alginate-embedded fish islets were encapsulated in permselective (25-kDa) cellulose membranes and implanted ip in six STZ-diabetic nude mice. On the following day, all recipients became normoglycemic and their n-FBG remained normal for 7 days. In one animal, the n-FBG was < 200 mg/dl for 14 days and subsequent removal of the capsule raised the n-FBG to the pre-Tx level. Finally, it was found that fish islets can be cultured at 37 degrees C for extended periods of time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791333 TI - Endotoxin tolerance alters phospholipase C-gamma 1 and phosphatidylinositol-3' kinase expression in peritoneal macrophages. AB - Although the molecular signaling mechanisms underlying macrophage endotoxin (LPS) responsiveness are not fully understood, alterations in intracellular phosphatidylinositol (PI) metabolism appear to contribute. We evaluated the effects of endotoxin tolerance (ET) induction upon peritoneal macrophage (PM) expression of the principal PI enzymes phospholipase PLC-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3'-kinase (PI-3-K). Rats received either 5 mg/kg LPS (ET) or phosphate-buffered saline (nontolerant, NT) which enabled 88% of ET and 25% of NT to survive a 25 mg/kg LPS dose 3 days later. PM were harvested by lavage on Day 3 from both ET and NT rats. Following overnight culture, 5 x 10(6) PM in serum-free media were stimulated with 5 ng/ml LPS for 0 to 30 min. Cell lysates fractionated by SDS-PAGE were transferred to nitro-cellulose and blotted with PLC-gamma 1, PI-3'-K, and phosphotyrosine (4G10) monoclonal antibodies. Western immunoblots were developed by enhanced chemiluminescence and quantitated by densitometry. Unlike NT cells in which PLC-gamma 1 was expressed constitutively and increased with LPS stimulation, PLC-gamma 1 expression in ET cells stimulated with LPS was markedly reduced in three separate experiments. In contrast, ET cells expressed considerably higher concentrations of PI-3'-K to NT cells. Patterns of protein tyrosine phosphorylation were similar in both NT and ET cells regardless of LPS stimulation. The development of endotoxin tolerance decreased PLC-gamma 1 expression and markedly amplified PI-3'-K expression in macrophages. PI-3'-K-generated second messengers may contribute to unique signaling pathways responsible for tempered cellular responses to LPS. PMID- 7791334 TI - PMNs primed for superoxide release and increased CD11b expression do not sequester in normal lung. AB - Our previous work has implicated platelet activating factor (PAF)-induced neutrophil (PMN) priming and increased CD11b/CD18 receptor expression in the pathogenesis of lung injury following gut ischemia/reperfusion (I/R). In this model CD11b blockade abrogates lung injury but does not alter PMN priming or pulmonary leukosequestration. We, therefore, hypothesized that PAF-stimulated PMN priming and CD11b expression are insufficient to promote lung PMN sequestration. Normal rat PMNs, labeled with 51Cr, were incubated with PAF (10 ng/ml) to induce priming for superoxide (O2-) generation and enhance CD11b expression. Gut I/R animals underwent superior mesenteric artery occlusion for 45 min. 51Cr-labeled PMNs (2 x 10(7)) were injected iv. Study groups, consisting of (a) normal/control, (b) sham/laparotomy, and (c) gut I/R, were given either normal or PAF-treated PMNs. PAF-primed PMNs had increased 2- release and CD11b expression, but did not sequester in the lungs of normal rats. However, following gut I/R PAF treated PMNs sequestered in the pulmonary bed. These data suggest that PAF priming for O2- generation and increased CD11b expression are insufficient alone to promote PMN sequestration in the lung. Rather, additional factors generated by gut I/R are necessary for this process. PMID- 7791335 TI - The structured clinical instruction module: a novel strategy for improving the instruction of clinical skills. AB - We have previously shown that both medical students and residents demonstrate numerous important deficits when evaluating patients with abdominal complaints. To address these deficits, we implemented a pilot instructional program derived from the Objective Structured Clinical Examination. Fifty third-year medical students were presented with a 1-hr Structured Clinical Instruction Module (SCIM) of five stations, each station addressing a different aspect of the surgical evaluation of the abdomen. Simulated patients were present at two of the stations. Faculty from appropriate disciplines were present at the stations to provide standardized instruction according to predetermined curricular objectives. The medical students evaluated the SCIM for its specific characteristics, and they evaluated each of the five stations for its efficacy in increasing their clinical skills. All the specific aspects of the SCIM were given a rating significantly higher than neutral (P < 0.0001). Students agreed most strongly that the faculty were well prepared for the SCIM and that the faculty were enthusiastic. All of the SCIM stations were given a rating significantly higher than average (P < 0.0001). When compared to a conventional workshop, the SCIM scored significantly higher on all three common evaluation items. The SCIM was very well received by medical students as a format for clinical instruction. This unique modification of the Objective Structured Clinical Examination has potential for teaching important clinical skills that are not consistently mastered within current surgical curricula. PMID- 7791336 TI - A comparison of spontaneous versus induced tolerance in an experimental model of rat hepatic allograft transplantation. AB - In some rodent haplotype combinations, spontaneous tolerance (ST) develops after orthotopic liver transplantation (OLT) without any immunosuppression [e.g., Lewis (Lew, RT1) into Wistar Furth (WF, RT1u)] whereas in other combinations vigorous, progressive rejection rapidly leads to the death of the recipients. We (and others) have induced tolerance (IT) in a rejecting strain combination [Dark Agouti (DA, RT1a) into Lew] by intrathymic inoculation of donor bone marrow cells and 1 cc of antilymphocyte serum (ALS) 7-14 days prior to OLT. We hypothesized that cellular immunity in the two groups of animals was similar. We first compared survival in each group of animals and found that there was no difference in the number of animals surviving > 100 days (8/11 vs 16/17, ST vs IT, respectively, P = 0.11). Liver function studies were similar in these animals at 2 and 4 weeks after OLT and comparable to syngeneic Lew into Lew OLT animals, but significantly lower than in the rejecting DA into Lew combination treated with only ALS. Animals that were unresponsive to their allografts demonstrated donor specific tolerance by the acceptance of donor strain (n = 4, ST and IT) and rejection of third party (n = 1 and n = 2, ST and IT groups, respectively) heterotopic heart allografts. One-way mixed lymphocyte cultures (MLC) of peripheral blood lymphocytes against donor and third party antigen were suppressed to donor and third party stimulators versus the MLC of unmanipulated animals. Naive host strain responder lymph node cells and purified T cells demonstrated strong proliferative responses to donor strain antigen in both the ST and IT animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791337 TI - Collagen matrix cisplatin prevents local tumor growth after margin-positive resection. AB - The extent of a tumor, sometimes combined with its anatomic location, can compromise the surgeon's ability to obtain clear margins of resection. Regional recurrence of a tumor in the resection bed frequently produces significant local morbidity and limits patient survival time and quality of life. A positive margin resection model was created by induction of perinephric VX-2 tumors in New Zealand white rabbits followed by unilateral nephrectomy with grossly positive margins in the retroperitoneum. Resection bed injection of a novel collagen matrix with cisplatin (CDDP) and epinephrine prevented tumor recurrence in all treated animals. In contrast, control animals treated with CDDP alone, CDDP and epinephrine alone, or the collagen matrix with epinephrine had bulky tumor recurrence in the resection bed. Resection bed tissue levels of platinum were determined by flameless absorption spectrophotometry at 1, 4, and 7 days following nephrectomy and injection of the collagen matrix, CDDP, and epinephrine or CDDP and epinephrine without the collagen matrix. Significantly higher resection bed drug levels of platinum were achieved through the use of the novel collagen matrix than through the use of CDDP and epinephrine alone (P < 0.05). The results of this study indicate that tumor bed treatment with CDDP and a unique collagen matrix drug-delivery vehicle produces prolonged high resection bed levels of platinum and prevents local tumor recurrence. PMID- 7791338 TI - Prostanoids inhibit Kupffer cell nitric oxide synthesis. AB - Kupffer cells are the largest population of fixed tissue macrophages in the body and produce a number of mediators that are involved in host defense. These mediators include cytokines such as tumor necrosis factor-alpha and interleukin 1, prostaglandins, oxygen radicals, and nitric oxide. Prostaglandins are produced by adjacent endothelial cells in addition to Kupffer cells and regulate a number of cellular functions in a wide array of cells, but their role in nitric oxide synthesis is controversial. We studied the role of prostaglandins in regulating lipopolysaccharide (LPS)-induced nitric oxide synthesis in cultured rat Kupffer cells. Prostaglandin E2 (PGE2) inhibited Kupffer cell nitric oxide synthesis in a dose-dependent fashion in both 24- and 48-hr cultures. The effect of PGE2 persisted at low and high LPS concentrations. Prostaglandin analogues as well as other prostanoids also inhibited Kupffer cell nitric oxide synthesis. These data show that exogenous prostaglandins suppress Kupffer cell nitric oxide synthesis and may represent an important endogenous regulator of nitric oxide production. PMID- 7791339 TI - Protein kinase C activation inhibits glutamate transport by endothelial cells. AB - The role of protein kinase C (PKC) in regulating endothelial cell glutamate transport was investigated. Glutamate transport studies were performed in confluent human umbilical vein endothelial cells which were treated with the phorbol ester 12-myristate 13-acetate (TPA, 0-1000 nM), a compound which directly activates PKC. TPA inhibited Na(+)-independent System xAG- glutamate transport by 70% but only slightly reduced Na(+)-dependent activity. The TPA-mediated reduction in transport activity was dose-dependent, beginning at 5 min and lasting for at least 24 hr. TPA inhibition of glutamate transport had two distinctive phases: an acute phase (< 1 hr, not affected by either cycloheximide or actinomycin D) in which TPA decreased System xAG- glutamate transporter affinity (TPA Km = 522 +/- 25 microM vs control Km = 329 +/- 85 microM, P < 0.01) but did not alter transporter capacity (TPA Vmax = 4426 +/- 230 pmole/mg/min vs control Vmax = 4535 +/- 750 pmole/mg/min, P = NS) and a chronic phase (4-24 hr) in which TPA inhibition of glutamate transport was due to a reduced transporter capacity (Vmax = 2895 +/- 570 pmole/mg/min) without altering transporter affinity (Km = 370 +/- 60 microM glutamate) and was abrogated by cycloheximide or actinomycin D. The protein kinase C inhibitor chelerythrine chloride abrogated TPA's inhibition effect in both the acute and chronic phases. These data indicate that protein kinase C activation decreases glutamate transport in human umbilical vein endothelial cells via protein synthesis dependent and independent mechanisms. PMID- 7791340 TI - Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. AB - Our in vivo model of mesenteric ischemia/reperfusion (I/R) has shown that the gut serves as a priming bed for neutrophils (PMN). Activation of phospholipase A2 (PLA2) during ischemia temporally precedes PMN sequestration in the gut and the appearance of primed PMN in the portal circulation. Therefore, we hypothesized that reperfused gut secretes platelet activating factor (PAF) via PLA2 activation that is responsible for increased PMN chemotaxis and priming for superoxide (O2-) generation. Sprague-Dawley rats underwent gut ischemia/reperfusion (45 min SMA occlusion/2 hr reperfusion) or sham laparotomy. Distal ileum was harvested, rinsed with bacteriostatic saline/neomycin, and incubated for 1 hr at 37 degrees C in RPMI 1640 and the cell-free supernatant was collected. Normal human PMNs, isolated by plasma-Percoll gradients, were pretreated with or without a PAF receptor antagonist (WEB 2170). Chemotaxis toward gut supernatant was then measured by the agarose method. Additionally, PMNs were preincubated with or without WEB 2170 and their O2- release in response to 1 microM FMLP was measured by the Vmax of SOD-inhibitable cytochrome c reduction. Reperfused gut produced a chemotactic index of 2.1 +/- 0.1 compared to 0.2 +/- 0.9 following sham laparotomy (P < 0.05); this was reduced to 0.4 +/- 0.9 with PAF receptor blockade. Similarly, gut I/R supernatant primed PMNs for O2- (P < 0.05) compared to laparotomy, and this effect was abrogated by a PAF antagonist. These data suggest that reperfused gut can elaborate PAF which chemoattracts and primes PMNs for O2- generation. PMID- 7791341 TI - Impaired release of gallbladder calcitonin gene-related peptide in human gallstone disease. AB - Calcitonin gene-related peptide (CGRP) is a neurotransmitter present in the peripheral ends of sensory neurons of the gut and may modulate reflexes of the enteric nervous system. We studied the release of CGRP in normal human gallbladders and in those containing gallstones to test the hypothesis that abnormalities of regulation of CGRP release participate in gallstone formation. Human gallbladder strips were obtained from histologically normal organs removed during liver surgery (n = 8) or from patients operated upon for symptomatic cholelithiasis (n = 14). After removal of the mucosa, muscle strips were superfused with oxygenated Kreb's buffer in an organ bath at 37 degrees C. Pharmacologic agents were added to the superfusate and samples were collected at 2-min intervals for analysis. CGRP release was measured by a sensitive and specific radioimmunoassay and adjusted for tissue weight. In normal gallbladders, CGRP release was stimulated sixfold over basal by capsaicin (10(-5) M) to 363 +/- 75 pg per gram of muscle per 2 min. This release was abolished by addition of somatostatin (SS) or the neural blocker tetrodotoxin (TTX). Lesser degrees of CGRP release were observed after nonspecific stimulation with K+ or phosphodiesterase inhibition with caffeine. In gallbladders with gallstones, capsaicin-induced CGRP release was 74 +/- 16 pg per gram of muscle per 2 min (20% of normal, P < 0.001). Release induced by caffeine and K+ was also inhibited compared to normal gallbladder strips. Release of CGRP from diseased strips was abolished by TTX and inhibited by SS to degrees similar to normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791342 TI - Perioperative growth hormone improves wound healing and immunologic function in rats receiving adriamycin. AB - Administration of perioperative growth hormone may reverse alterations in wound healing and immunologic function in animals receiving chemotherapy. F344 rats were randomized into three groups: Control (n = 12), Chemo (n = 13), and Chemo + GH (n = 12). Human growth hormone (GH) (3 mg/kg sc bid) was begun on Day 0 and continued for 2 weeks. On Day 7, all animals underwent a standardized midline laparotomy, gastrotomy, and placement of a subcutaneous wound sponge. In addition, a single dose of adriamycin (5 mg/kg i.v.) was administered to those animals receiving chemotherapy. On Day 12, right hindlimb footpads were challenged with 50 micrograms of dinitrochlorobenzene. On Day 14, bursting strengths of the laparotomy and gastrotomy were measured. The wound sponge and gastric anastomosis were analyzed for hydroxyproline (OH-Pro) content. Animal spleens were weighed and splenocytes harvested for NK cell activity. Delayed type hypersensitivity (DTH) is reported as percentage of hind-limb foot pad swelling (%FPS). Data are expressed as means +/- SD and comparisons by ANOVA. The laparotomy bursting strength (mm Hg) in the Chemo + GH group (81 +/- 14) was significantly higher than that in the Chemo group (66 +/- 15, P < 0.05). The anastomotic tissue OH-Pro levels (mumole/g dry tissue) in the Chemo + GH group (107.9 +/- 15.2) were significantly higher than those in the Chemo group (62.9 +/ 8.5, P < 0.001). GH increased splenic weights (mg) over those of Chemo (0.50 +/- 0.13 vs 0.37 +/- 0.05, P < 0.05). NK cell activity (% killing) was significantly elevated in the Chemo+GH group compared to that in Chemo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791343 TI - Independent signal transduction pathways for IL-1 and TNF in LPS-tolerant macrophages. AB - Macrophages rendered "tolerant" by pretreatment with low-dose endotoxin (LPSp) release less TNF and more IL-1 in response to a second activating endotoxin exposure (LPSa). We hypothesized that LPSp pretreatment alters signal transduction pathways for TNF and IL-1 independently. The effect of pretreatment with LPSp alone was compared to pretreatment with LPSp plus defined second messenger pathway agonists or antagonists. Murine peritoneal macrophages were pretreated in vitro for 4 hr with LPSp or PMA or LPSp plus protein kinase C inhibitor (PKCi) or 8-bromo-cAMP. Cells were then washed and cultured with medium alone for 20 hr. Macrophages were also pretreated with LPSp plus indomethacin for the total 24-hr pretreatment interval. Cells were then stimulated for 24 hr with LPSa, after which supernatant TNF and IL-1 were measured by bioassay. In the absence of LPSp, mediators were increased by LPSa in a dose-dependent manner. LPSp pretreatment inhibited TNF and augmented IL-1 in response to LPSa. Pretreatment with PMA partially reproduced LPSp pretreatment. Pretreatment with PKCi alone increased both TNF and IL-1 release by LPSa. The combination of LPSp plus PKCi pretreatment further enhanced IL-1 release without affecting TNF inhibition. The addition of indomethacin had a similar effect. The combination of LPSp plus 8-bromo-cAMP blocked the augmentation of IL-1 without changing TNF inhibition. Macrophage endotoxin tolerance following LPSp pretreatment alters LPSa-triggered TNF and IL-1 release by independent signal transduction pathways. PMID- 7791344 TI - Tumor necrosis factor stimulates system XAG- transport activity in human endothelium. AB - System xAG- is responsible for the carrier-mediated Na(+)-independent transport of anionic amino acids such as glutamate and aspartate across the plasma membrane of cells. In order to examine a possible role for cytokines in regulating System xAG- activity, the effect of TNF on [3H]glutamate transport in cultured human umbilical vein endothelial cells (HUVECs) was studied. Carrier-mediated glutamate uptake was accomplished by two high-affinity carriers, predominantly by a Na(+) independent carrier (System xAG-, 75% of total glutamate uptake) and, to a lesser extent by a Na(+)-dependent carrier (System XAG-, 24% of total uptake). TNF treatment (10 ng/ml for 10 hr) resulted in an 80% increase in Na(+)-independent glutamate transport activity with no change in System XAG- activity. The TNF stimulatory effect was blocked by actinomycin D and cycloheximide. TNF treatment increased System xAG- glutamate transporter Vmax by 51% (control Vmax = 2359 +/- 345 pmole/mg protein/min vs TNF Vmax = 3569 +/- 436 pmole/mg protein/min, P < 0.01) without altering transporter affinity (control Km, 229 +/- 40 microM glutamate vs TNF Km = 224 +/- 60 microM glutamate, P = NS). The protein kinase C (PKC) inhibitor chelerythrine chloride had no effect on the TNF-stimulated glutamate transport, indicating that the augmented glutamate transport was not mediated by PKC activation. These data indicate that the TNF-stimulated glutamate transport in HUVECs requires do novo protein synthesis, possibly of the System xAG- transporter protein itself. Accelerated glutamate transport provides a precursor for the biosynthesis of macromolecules and glutamine. PMID- 7791345 TI - Changes in muscle mechanics during chronic conditioning for cardiomyoplasty. AB - Chronic repetitive stimulation of skeletal muscle causes significant changes in contractile mechanics and makes the muscle fatigue resistant. The purpose of this study was to quantify the magnitude and time course of these changes. One latissimus dorsi muscle from each of 28 mongrel dogs was stimulated in situ at 1 Hz for 0, 3, 7, 14, 21, 42, or 70 days. Changes in isometric and isotonic mechanical performance were measured as a function of conditioning time. Isotonic force and velocity data were fitted to the Hill equation to obtain Vmax. The most striking early change was a 30 and 26% decline in muscle mass and cross-sectional area, respectively. Coincident with this was an approximate 40% decline in tetanic and twitch tension. There was a similar decline in the rates of rise and fall of twitch and tetanus tensions (+dT/dt and -dT/dt). The decline in tetanus +dT/dt and -dT/dt followed a similar time course, suggesting that these muscle functions were under similar influences. Calculation of the isometric force data per unit of cross-sectional area minimized the effect of stimulation on isometrically measured muscle function but did not eliminate it. Fusion frequency declined 52% with conditioning. The increases in time-to-peak twitch tension and half-relaxation time were independent of cross-sectional area. Time-to-peak twitch tension and half-relaxation time increased after 7 days of stimulation and became maximal after 42 or 70 days, respectively. Time-to-peak tetanus tension was unchanged by muscle conditioning. Changes in the force-velocity relationship began after 3 days of stimulation, changed very little between 3 and 21 days of stimulation, and showed another change after 42 and 70 days of stimulation. It may be possible to better modify the muscle for dynamic cardiomyoplasty by pharmacological or stimulation regimens once the mechanism of fiber switching is better understood. PMID- 7791346 TI - Hemorrhage affects the ability of murine peritoneal macrophages to alkanize intracellular pH in acidic environments. AB - Although departures from the normal physiologic pH range, associated with states of shock, injury, and/or infection are thought to impair phagocytic function and chemotaxis, it remains unknown if the ability of the peritoneal macrophage (pMo) to gate H+ is affected following hemorrhagic shock. To study this, male C3H/HeN mice were bled to a BP of 40 mm Hg and maintained at that level for 1 hr. Following resuscitation with the shed blood plus 2x that volume as Ringer's lactate, pMo was harvested via lavage in bicarbonate-free RPMI 1640 and enumerated to 2 million cells/ml. PMo was then loaded with a pH-sensitive dye, BCECF (2 micrograms/ml), for 20 min and washed with a buffered Na+ solution followed by phorbol myristate acetate stimulation (0.5 micrograms/ml). The capacity of the pMo to gate H+ at an external pH of 7.35 or 6.7 was assessed via fluorescence spectrophotometry. PMo from hemorrhaged animals had a decreased ability to alkalinize intracellular pH compared to that of control (P < 0.05), indicating a decreased ability of these Mo to maintain internal pH in an acidic environment following hemorrhage. In additional studies, oxidative burst capacity was determined by employing a commercially available fluorogenic substrate, (Fc Oxiburst), which fluoresces during intracellular oxidation. Fluorescence (U x 10(6)) was assessed with the ACAS 570 laser cytometer, after 0 and 200 sec following ingestion of substrate. The results demonstrate that pMo oxidative burst capacity was also decreased following hemorrhage and resuscitation. PMID- 7791347 TI - Endogenous nitric oxide promotes ileal absorption. AB - BACKGROUND/AIMS: Nitric oxide (NO) is generated in vascular endothelium and enteric neural plexuses from L-arginine by the action of nitric oxide synthase (NOS). This study tested the hypothesis that NO is a modulator of ileal water and ion transport. METHODS: NADPH diaphorase staining was performed on fixed frozen sections of canine ileum. Absorption studies (n = 80) were performed in five dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [14C]PEG was used to calculate absorption of water, ions, and glucose from the TVF. Experiments comprised three 1-hr periods: basal, drug infusion, and recovery. Drugs infused luminally at 5 x 10(-4) mol/liter included L-ARG (NOS substrate), L-NAME (NOS inhibitor), L-ARG/L-NAME combination, D-ARG (inactive enantiomer of L-ARG), L-LYS (basic amino acid control for L-ARG), and SNAP (NO donor). RESULTS: NADPH diaphorase staining indicated NOS activity in the ileal mucosa and submucosa. L ARG and SNAP caused significant increases in water and ion absorption, whereas L NAME caused significant decreases. The prosecretory effect of L-NAME was completely reversed by synchronous L-ARG. D-ARG and L-LYS had no significant effects. No infused agent influenced [14C]PEG recovery. CONCLUSIONS: Inhibition of endogenous NO synthesis by L-NAME causes a prosecretory response for water and ions, which can be reversed by the administration of NOS substrate L-ARG. These results are consistent with the hypothesis that endogenous NO maintains a proabsorptive influence on water and ion transport in the ileum. PMID- 7791348 TI - Attenuation of the endotoxin-stimulated increase in hepatic amino acid transport with a glucocorticoid receptor antagonist. AB - The role of the glucocorticoid hormones in mediating the accelerated hepatic amino acid transport that is characteristic of endotoxemia was investigated. To determine the role of these steroid hormones, rats that received endotoxin (LPS) were pretreated with the glucocorticoid receptor antagonist RU38486. The activities of the Na(+)-dependent amino acid transport systems A, ASC, and N and the Na(+)-independent systems L, y+, n, b0,+, and asc in hepatic plasma membrane vesicles were measured 4 hr after exposure to LPS. Endotoxin treatment resulted in time- and dose-dependent 5-fold (System A), 2.5-fold (System N), 2.6-fold (System ASC), and 2-fold (System y+ and b0,+) increases in transport activity attributable to an increase in carrier Vmax. The activities of L, asc, and n were unchanged by LPS administration. Pretreatment of endotoxemic animals with RU38486 attenuated the LPS-induced enhancement in transport activity by 20-60% by diminishing carrier Vmax, with no effect on transport Km. We conclude that the marked increase in hepatic amino acid transport activity that occurs during endotoxemia requires participation of the glucocorticoid hormones. PMID- 7791350 TI - Human pancreatic cancer growth is inhibited by peptide YY and BIM-43004-1. AB - Exogenous peptide YY (PYY) decreases pancreatic exocrine secretion, pancreatic endocrine function, and pancreatic blood flow. We hypothesized that pancreatic cancer cell growth may be inhibited by PYY and a new synthetic analog, BIM-43004 1. Two human pancreatic ductal adenocarcinomas, PANC-1 and Mia PaCa-2, were examined in tissue cultures. Viable pancreatic cancer cells were counted with trypan blue on a hemocytometer slide. Cells (10K, 20K, 40K, and 80K) were cultured and allowed to grow for 36 hr (n = 14/cell concentration). Pancreatic cancer cells received either PYY or BIM-43004-1 at various concentrations. Control tissue cultures received an equivalent volume of saline inoculation. After incubation with the above peptides for 24 hr, MTT tetrazolium bromide was added to assay mitochondrial activity of pancreatic cancer cells in response to PYY and its analog. MTT assay reveals a significant decrease in pancreatic cancer cell growth when PYY and BIM-43004-1 are added to the cell culture. Results in Mia PaCa-2 reveal a 24% cell growth reduction after exposure to PYY and a 23% reduction in cell growth when treated with BIM-43004-1. In PANC-1 cells, a 25% reduction in growth of cells is noted after PYY treatment and a 24% reduction in growth after BIM-43004-1 treatment. (means +/- SEM, P < 0.05 by Student's t test). Our results reveal a significant reduction in human ductal pancreatic cancer growth when treated with either PYY or its analog, BIM-43004-1. These agents may be useful hormonal adjuncts in the chemotherapy of pancreatic adenocarcinoma. PMID- 7791349 TI - Gangliosides and spinal cord ischemia secondary to aortic cross-clamping in the rat model. AB - Gangliosides, complex glycolipids of the nervous system cell membranes, have been found effective both in reducing the degree of ischemic injury and in stimulating neuronal regeneration during the recovery period. In order to investigate their neuroprotective effect during spinal cord ischemia, 60 male Sprague-Dawley rats underwent occlusion of the thoracic aorta and both subclavian arteries for 13 min. In the postoperative period, function of hindlimbs was appraised, daily for 30 days, by a deficit score (0-15). The animals were then killed and spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. The rats received intraperitoneal injection of placebo (n = 29) or GM-1 30 mg/kg (n = 31) daily, from 2 days prior to surgery to 15 days after. The scores of each group for each day were analyzed by repeated measures analysis of variance. The rate of recovery was better for GM-1 (P < 0.001) from the 15th to the 30th day. A trend was seen toward lower scores in the GM-1 group (P = 0.056). Mean histologic scores (placebo = 1.14 +/- 0.23 SE, GM-1 = 1.58 +/- 0.22 SE) did not differ (Wilcoxon, P = 0.17). The present data support the hypothesis that functional improvement after spinal cord ischemia due to aortic occlusion is enhanced by the administration of gangliosides. Optical microscopy could document only irreversible injury and might not be sensitive enough to detect subtle changes during recovery of neural elements. PMID- 7791351 TI - Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. AB - Using a rat lung model, we sought to characterize the time course for ischemia reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P < 0.0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia (< 75/mm3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P < 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events. PMID- 7791352 TI - A model of intestinal ischemia in the neonatal rat utilizing superior mesenteric artery occlusion and intraluminal platelet-activating factor. AB - The human premature newborn is susceptible to necrotizing enterocolitis (NEC) in the first 1 to 3 weeks of life, a time when the gastrointestinal tract is structurally and functionally premature. Studies of NEC are hampered by the lack of a standard, reproducible model in newborn animals. The purpose of this study was to produce a model for intestinal ischemic injury in newborn rats. On Days 14, 18, 22, and 26 of life, newborn rats (10/day) were subjected to 1 hr of superior mesenteric artery occlusion with a microaneurysm clip. Platelet activating factor (PAF, 50 micrograms/kg) was injected into the lumen of the proximal small intestine after occlusion was initiated. Control animals (10/day) underwent sham laparotomy on Days 14, 18, 22, and 26. Animals were autopsied upon demise (7.6 +/- 0.7 hr) or at 24 hr. The intestine was inspected for gross ischemic changes and samples were taken for histology and myeloperoxidase (MPO, an index of neutrophil infiltration). Ischemic injury was graded in a blinded fashion, by a pathologist, using a scale from 0 to 4 (0, no injury; 4, full thickness necrosis). All animals in the experimental groups had evidence of histologic injury (mean +/- SEM) on Days 14 (1.0 +/- 0.0), 18 (2.5 +/- 0.5), 22 (3.6 +/- 0.3), and 26 (3.1 +/- 0.5). The sham-operated control animals had no injury (P < 0.0001). MPO levels (U/g protein) on Days 18 (27.2 +/- 1.7 vs 13.9 +/ 2.3), 22 (40.9 +/- 5.4 vs 7.6 +/- 0.8), and 26 (29.3 +/- 4.4 vs 7.6 +/- 1.0) were significantly higher in experimental groups vs controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791354 TI - Lymphocyte-derived cytokines augment macrophage tumor necrosis factor-alpha and interleukin-6 secretion during experimental gram-negative bacterial sepsis. AB - Although lymphocyte-derived cytokines are known to augment macrophage cytokine production in vitro, their effect on macrophage tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) secretion during gram-negative bacterial sepsis has not been characterized. The purpose of this study was to examine the effect of lymphocyte-derived cytokines on macrophage TNF-alpha and IL-6 secretion during gram-negative bacterial peritonitis. To examine this problem, uninfected and infected mice were studied. Mice were infected with Escherichia coli O111:B4 and two subgroups were examined consisting of those pretreated iv 1 hr prior to bacterial challenge with either (1) saline or (2) anti-E. coli O111:B4 LPS mAb 2A3, the latter administered to abrogate the effects of LPS in vivo. Thus, three groups of mice were studied in relation to pretreatment and infectious challenges: (1) saline/saline (control); (2) saline/E. coli (saline); and (3) mAb 2A3/E. coli (mAb 2A3). Nonadherent splenocytes (> 95% lymphocytes by histologic staining criteria) harvested 16 hr later from mice in each group were incubated in culture ex vivo for 3 hr to obtain supernatants containing lymphocyte-derived cytokines. These supernatants containing lymphocyte-derived cytokines then were incubated in vitro with naive splenic macrophages with or without E. coli O111:B4 LPS. Macrophage TNF-alpha and IL-6 levels were determined using L929 and B9 bioassays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791355 TI - Efferent limb myoneural and luminal continuity and postgastrectomy gastric emptying. AB - Delayed gastric emptying and altered upper gut transit or both are common following Roux-en-Y gastrojejunostomy and are thought to be due to altered efferent limb transit secondary to isolation of the Roux limb from the duodenal pacemaker. We postulated that preservation of myoneural continuity of the Roux limb with the duodenal pacemaker would enhance solid gastric emptying, while division of the afferent limb of a Billroth II gastrojejunostomy (B-II), isolating the efferent jejunal limb from the duodenal pacemaker, would slow gastric emptying. Solid gastric emptying was measured in 14 dogs, who then underwent gastric vagotomy and antrectomy. Eight animals were reconstructed with a Roux-en-Y gastrojejunostomy, preserving myoneural but not luminal continuity of the Roux limb with the afferent limb via a muscularis bridge, while six dogs underwent standard B-II gastrojejunostomy. Serosal electrodes were placed on the afferent and efferent jejunal limbs. Gastric emptying was restudied, with fed and fasted myoelectric recordings. The bridge was then divided to create a standard Roux, while the afferent limb was transected and reanastomosed just proximal to the gastrojejunostomy in the B-II dogs to isolate the efferent limb from the duodenal pacemaker, with repeat studies. Bridge dogs had delayed solid gastric emptying compared to their preoperative state, despite normal efferent limb motility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791353 TI - Dibutyryl cAMP reduces nonparenchymal cell damage during cold preservation of rat livers. AB - Sinusoidal lining cells are the main target for cold preservation injury and are further damaged with reperfusion. Different agents known to increase intracellular cAMP levels have been shown beneficial. This study was designed to assess the possible protective effect of a cAMP analogue on nonparenchymal cells of rat livers, during cold storage and during reperfusion. Parameters reflecting the status of the liver microvasculature were analyzed. The initial effluent collected after preservation reflects release during the cold storage period; therefore we measured interleukin-1 (IL-1) and endothelin-1 (ET-1) levels in these samples in order to detect and quantitate the degree of activation and/or disruption of Kupffer and sinusoidal endothelial lining cells. Rat livers were harvested after in situ flush with Ringer's lactate with or without 2 mM dibutyryl cAMP, excised, and stored in the same solution at 4 degrees C. After 6 hr, livers were perfused with Krebs-Henseleit buffer for 90 min. Physiological parameters were monitored throughout the perfusion. Perfusate samples were collected every 30 min for RIA measurements of IL-1 and ET-1. Treatment resulted in a significant decrease in release of ET-1 and IL-1 during storage. Likewise, livers treated with cAMP had a significantly improved bile output and decreased portal vein resistance during reperfusion. The beneficial effect granted by the analogue during cold storage and reperfusion was evident on parenchymal and nonparenchymal cells. Levels of ET-1 and IL-1 in the caval effluent confirm and quantitate preservation damage. PMID- 7791356 TI - GI hormonal changes in diabetes influence pancreatic cancer growth. AB - Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor dependent fashion. PMID- 7791357 TI - Differential TNF secretion by wound fibroblasts compared to normal fibroblasts in response to LPS. AB - Fibroblasts cultured from wound sites have been shown to have an altered phenotype compared to normal dermal fibroblasts and are generally regarded as target cells of the cytokine response at sites of injury. This study was undertaken to determine whether wound fibroblasts can contribute to proinflammatory cytokine production in wounds and, in particular, whether they are capable of secreting TNF. Wound fibroblasts were cultured from polyvinyl alcohol sponges implanted subcutaneously for 2 weeks in Balb/c mice. Fibroblasts harvested from the skin and subcutaneous tissue of untreated mice served as a control population of cells. All cells were passaged at least twice and then stimulated with a dose range of LPS. Supernatants were harvested 8 hr following stimulation and TNF was assayed using a standard L929 cell-killing assay. There was a significant TNF response to LPS by wound fibroblasts, evident as early as 4 hr following exposure to LPS and associated with an upregulation of TNF mRNA. Normal dermal fibroblasts did not secrete any measurable amounts of TNF in response to LPS. The results indicate that wound fibroblasts generate a brisk TNF response to stimulation with LPS, in contrast to normal subcutaneous fibroblasts. These data reveal an additional unique property of wound-harvested fibroblasts and suggest a possible contributing mechanism to disordered wound healing in the face of infection or conditions characterized by excessive fibrosis. PMID- 7791359 TI - A computer-based system for the measurement of membrane capacitance to monitor exocytosis in secretory cells. AB - A software-based system for real-time measurement of membrane capacitance was developed for monitoring exocytosis in a single cell. The IBM PC compatible software, linked to an interface box, provides capacitance measurement capabilities to a patch-clamp setup utilizing a Labmaster data acquisition board. In order to measure the time-dependent changes in membrane capacitance, the system uses a software-based phase detector which isolates capacitive membrane current from a cell subject to sinusoidal voltage stimulation. The sampling program can monitor changes in membrane capacitance in response to depolarizing voltage steps, intracellular calcium stimulation, or drug application. A separate analysis program was constructed to implement the quantitative analysis, plotting and exporting of the capacitance, conductance and current data acquired by the sampling program. PMID- 7791358 TI - Pulmonary hypertension in acute lung injury is due to impaired vasodilation with intact vascular contractility. AB - The major hemodynamic feature of acute lung injury (ALI) is pulmonary hypertension. Both endothelial-dependent and -independent pulmonary vasorelaxation is impaired in ALI due to endotoxemia. We hypothesized that endotoxemia selectively impairs relaxation of the pulmonary artery but does not impair contractility of pulmonary vascular smooth muscle (VSM). Our purpose was to determine the effect of endotoxemia (ETX) on the contractile response of pulmonary VSM to (1) tubular depolarization (KCl), (2) alpha 1-adrenoreceptor stimulation (phenylephrine, PE), (3) 5HT2 receptor stimulation (serotonin, 5HT), and (4) prostaglandin F2 alpha receptor stimulation. Pulmonary artery rings were isolated from rats 6 hr after injection of ETX, 20 mg/kg ip (n > or = 6), or saline (n > or = 6) and suspended on tensiometers in individual organ baths. Endothelial-dependent cGMP-mediated relaxation was determined using the receptor agonist acetylcholine (ACh) in rings preconstricted with PE. Dose-response curves were generated to each contractile agonist. Statistical comparison was performed using one-way ANOVA with post hoc Bonferonni-Dunn, P < 0.05 accepted as significant. Relaxation to ACh was 96.4 +/- 1.3% in controls vs 21.4 +/- 3.1% (P < 0.05) in endotoxin-treated rats. Endotoxin did not affect the maximal tension in response to the contractile agonists nor did it change the concentration required to produce 50% contraction (EC50). From these data we conclude that endotoxemia causes a decrease in vasorelaxation to the endothelial-dependent receptor agonist acetylcholine but does not impair agonist-induced contractility of pulmonary VSM. This suggests that pulmonary hypertension in ALI is mediated by impairment of pulmonary vasodilation with preservation of VSM contractility. PMID- 7791360 TI - Application of 'nose-poke habituation' validation with post-trial diazepam- and cholecystokinin-induced hypo- and hypermnesia. AB - The present study describes the use of nose-poke habituation as a memory task and demonstrates that it is sensitive to hypo- and hypermnestic pharmacological treatments administered post-trial. Habituation of nose-poke behavior of rats was defined as a reduction in number of nose-pokes compared to baseline. It was measured using a board with 16 holes, to which animals were exposed on 2 consecutive days (baseline and test) for 10 min, respectively. After the first exposure, rats were injected intraperitoneally (i.p.) immediately or with a delay of 2.5 h with doses of diazepam (0.9-4.5 mg/kg) known to be hypomnestic, or cholecystokinin (CCK-8S; 0.2-25 micrograms/kg), which was reported to have memory facilitating effects. An enhancement of habituation in comparison with vehicle controls was interpreted in terms of a hypermnestic effect of the treatment. Conversely, hypomnestic action of the drug treatment was inferred from a reduced habituation. The results show that when diazepam was injected immediately post trial, the normal reduction in number of nose-pokes during test was prevented, indicative of a failure to habituate presumably due to an amnesia for the baseline/training trial. In contrast, enhanced habituation (facilitation of memory) was induced when CCK-8S was injected immediately post-trial, as reflected by a decrease in number of nose-pokes during test compared to control animals. The effects were not due to enduring proactive effects of the compounds on performance during test, since post-trial injections of diazepam or CCK-8S with a delay of 2.5 h did not have the effects that immediate post-trial injection had.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791361 TI - A statistically based method to generate response maps objectively. AB - One scheme to classify the physiological response properties of single units in the cochlear nucleus is based on the average discharge rate of the unit and is reflected in the distribution of excitatory and inhibitory regions in a frequency level map (response map) that spans the unit's receptive area (e.g., Evans and Nelson, 1973; Young and Brownell, 1976; Young and Voigt, 1982; Shofner and Young, 1985, Spirou and Young, 1991). Typically, discharge rate versus level curves are acquired at many frequencies and the investigator determines that a unit is excited or inhibited at a given level if the driven rate is above or below a spontaneous rate estimate by a specified criterion (for example, 20%). The investigator then encloses regions of excitation and inhibition where responses over adjacent frequencies and levels are consistent. In the present report, we describe an objective 3-step computer-based method to generate response maps: raw driven and spontaneous rate estimates are smoothed with a low-pass spatial filter; a unit is said to be excited or inhibited at a given level if the filtered driven rate is above or below the mean filtered spontaneous rate for that frequency by a specified criterion (percentage or statistical); and resultant response maps are median spatial filtered to eliminate spurious regions. The results shown here demonstrate that use of a statistical criterion provides a more reliable detection of excitation and inhibition than a 20% criterion, particularly when the variance of the rate estimates is high. Further, the statistically based method permits unit classification based on response map data that are more rapidly acquired with shorter duration stimuli (32 vs. 200 ms). Although this method is applied to units recorded in the dorsal cochlear nucleus, the technique may be applicable to studies of receptive fields and their plasticity in other systems. PMID- 7791362 TI - Intracranial pressure waveform indices in transient and refractory intracranial hypertension. AB - Analysis of data obtained by continuous computerized monitoring of intracranial pressure (ICP) in 109 adult patients with severe head trauma was performed to examine the pattern of change in indices of the ICP waveform. Indices derived from direct measurement of the ICP wave and obtained from a Fast Fourier Transform (FFT) were examined. Concurrent physiologic measurements were made. Two types of intracranial hypertension (ICH) were defined for comparison. 'Transient intracranial hypertension' occurred when an abrupt rise in ICP was followed by a return to below 25 mm Hg (n = 63). Increases in ICP that were progressive and led to neurologic deterioration and death were termed 'refractory intracranial hypertension' (n = 18). During transient ICH heart rate, arterial pressure, end tidal carbon dioxide and jugular venous oxygen saturation all increased, while these measures either were unchanged or decreased during refractory ICH. The pulse amplitude of the ICP wave increased in both types of ICHtn. Other changes in the waveform indices were consistent with this change in pulse amplitude. HFC responded differently to the two types of changes, with an increase during the transient changes and a decrease during the refractory changes. The differences in changes in physiologic measurements as ICH occurred in the 2 groups suggest that in refractory ICH cerebral blood flow is maintained against the mounting ICP, while in transient ICH the hypertension is caused by an increase in cerebral blood flow. The waveform indices do not discriminate between the two types of changes. PMID- 7791364 TI - The analysis of excitatory, inhibitory and other amino acids in rat brain microdialysates using microbore liquid chromatography. AB - Three microbore liquid chromatography (LC) assays for determination of amino acids in rat brain dialysates are described: one for separation of amino acids by gradient elution and electrochemical detection, one for analysis of GABA by isocratic elution and electrochemical detection, and one for fast measurement of glutamate and aspartate by gradient elution and fluorescence detection. The assays are reliable, reproducible and sensitive. In comparison with conventional LC, a 5-fold increase in sensitivity was obtained for GABA. Optimization of the derivatization chemistry and the microbore LC system are discussed, as well as important practical aspects. PMID- 7791363 TI - A preparation of the blowfly (Calliphora erythrocephala) brain for in vitro electrophysiological and pharmacological studies. AB - We describe a method for the preparation and maintenance of the blowfly (Calliphora erythrocephala) brain in a recording chamber under in vitro conditions in a semi-slice configuration. Large identification neurones in the posterior part of the 3rd optic lobe (lobula plate) can be penetrated easily with microelectrodes. The so-called vertical system (VS) cells which respond to vertical image motion in vivo could be encountered best because their axons are escorted individually by specific tracheae. Fluorescent stained cells show their natural shape as being in vivo. Electrophysiological properties of the cells investigated so far, i.e., resting potential (about -40 mV) and firing properties (single rebound spikes), are comparable to recordings in intact flies. Initial pharmacological experiments on VS cells in this preparation reveal that iontophoretical application of acetylcholine and carbamylcholine results in depolarization. VS cells also respond to bath-applied nicotine (1 microM) with a slow depolarization of their membrane potential in normal fly saline as well as in a Ca(2+)-free saline, suggesting direct cholinergic input via nicotinic receptors. The suitability of the preparation for a wide range of electrophysiological and pharmacological studies is discussed. PMID- 7791366 TI - A quantitative method for morphometric analysis in neuronal cell culture: unbiased estimation of neuron area and number of branch points. AB - The morphology and fine structure of neurons in vivo as well as in vitro are influenced by a variety of cell-adhesion and extracellular matrix molecules and soluble growth factors. To examine the effects of such molecules, we have developed a new method for the quantitation of several parameters associated with the morphology of neurons in culture. Whereas methods which have been traditionally used to perform quantitative morphometric analysis of neurons in vitro are often time-consuming and subjective, the methods we describe provide a rapid, efficient, and unbiased approach to morphometric analysis of cultured neurons. PMID- 7791365 TI - Studies on the 3-dimensional architecture of dendritic spines and varicosities in human cortex by confocal laser scanning microscopy and Lucifer yellow microinjections. AB - A method for 3-dimensional (3-D) visualization of dendritic spines and varicosities in human cortical neurons is described. Intracellular microinjection of Lucifer Yellow was used to display the morphology of dendrites on pyramidal and non-pyramidal neurons. Confocal laser scanning microscopy was used for imaging, and 3-D reconstructions and analysis of spines and varicosities were performed. The frontal, temporal, parietal and occipital cortices, and hippocampus in normal and pathological human brains were studied. Using this technique spines can be visualized from both sides of dendrites, which are 'hidden' in 2-D representations, and therefore not usually included in the extimation of dendritic spine density/total spine numbers. In patients with Rett's syndrome and some epilepsy patients, a regional loss of dendritic spines ('naked' dendrites) was found. These results will be included in the Human Brain Mapping Project. PMID- 7791367 TI - Miniature microdrive for extracellular recording of neuronal activity in freely moving animals. AB - The new design of a removable miniature microdrive for extracellular recordings of single-unit activity in freely moving animals with high-impedance electrodes is presented. The construction permits very simple installation and removal of the microelectrodes, rapid fixation of the microdrive on the animals skull and rapid removal after recording. The microdrive provides vertical positioning of the electrode without rotations and lateral shifts, stable recordings of single units for several hours and the possibility to change the penetration track 20-30 times in the same animal. The 3.2-mm diameter of the microdrive cylinder permits the installation of several units simultaneously. The weight of the microdrive with the base is 115 mg. The microdrive permits penetrations to any desired depth. PMID- 7791368 TI - Neuron labeling by extracellular delivery of horseradish peroxidase in vivo: a method for studying the local circuitry of projection and interneurons at physiologically characterized sites. AB - An anatomical method is described that yields individual neurons with continuously labeled dendrites and axons following the extracellular deposition of horseradish peroxidase (HRP) at neurophysiological recording sites in vivo. The method is a logical evolution of previous methods for iontophoretic delivery of HRP: Parameters critical to the ultimate concentration of HRP at the labeling site are reduced by an order of magnitude relative to standard practice. In successful cases one neuron or two in the immediate vicinity (50 microns) of recording sites is/are labeled. Labeling of other processes traversing the injection site, if any, is subliminal at highest light microscopic magnification. Due to the labeling of so few cells and the absence of other labeled processes, dendritic trees and local axonal arbors can be reconstructed without ambiguity. In addition to recovering neurons at sites characterized with physiological (e.g., sensory) stimuli, the method offers the further advantage of being fully compatible with subsequent electron microscopy. Both large (> 20 microns) and small (approximately 8 microns) neuron types and glia have been labeled. PMID- 7791369 TI - Isolation of mature olfactory neurones using retrograde labelling and flow cytometry. AB - Currently we can observe an increasing interest for epithelial olfactory neurones. Several laboratories are involved in elucidation of the odorant molecule recognition process and transduction cascade which brings information to the olfactory bulb. Others use this model, unique in mammals, to accumulate new knowledge on the neurogenesis phenomenon. Here we describe a simple and efficient method to purify mature olfactory neurone populations extracted from the nasal cavity. The approach relies on retrograde axonal tracing followed by flow cytometry sorting. For this purpose we inject a fluorescent dye (Fast Blue or diI C18(3)) in the olfactory bulb of adult rats. Seven days later, we extract the nasal turbinates and separate the mucosa from the subjacent lamina propria. The tissue is enzymatically dissociated and the labelled cells are sorted with a flow cytometer. Purification of the mature olfactory neurones varies from 80 to 99%. PMID- 7791370 TI - Determination of in vivo amino acid neurotransmitters by high-performance liquid chromatography with o-phthalaldehyde-sulphite derivatisation. AB - The measurement of amino acid neurotransmitters by high-performance liquid chromatography (HPLC) has emerged as a reliable and sensitive method. This paper describes a method which employs electrochemical (EC) detection of amino acid derivatives formed by a reaction with o-phthalaldehyde (OPA) in the presence of sulphite ions. This is discussed in relation to the problems of previously reported methods based on OPA derivatisation. Precise separation of the following 7 amino acid standards is achieved using isocratic elution: serine, glycine, taurine, glutamate, arginine, alanine and GABA, in order of increasing retention time. Total elution time is 25 min. Derivatisation proceeds at room temperature and the derivatives are stable for up to 5 h. This technique has the sensitivity to determine the concentrations of amino acid neurotransmitters in cerebrospinal fluid (CSF) and an in vivo microdialysis method is discussed for the detection of basal and potassium-stimulated levels of gamma-aminobutyric acid and glutamate from rat hippocampus. PMID- 7791371 TI - Massage and damage to lymphatics. PMID- 7791372 TI - Are peripheral lymphatics damaged by high pressure manual massage? AB - Massage of the foot in men and the hindpaw in dogs was performed by applying external pressures of 70-100 mmHg for a period of one, three, five, and ten minutes with a frequency of 25 strokes per minute. This protocol was performed on individuals without edema, on dogs with experimental lymphedema and men with post thrombotic venous edema. After ten minutes of forceful massage, focal damage of lymphatics was present. In a group of dogs with lymphedema and men with post thrombotic venous edema, the alteration of lymphatics was greater than in normal individuals and evident only after 3 to 5 minutes of massage. At first, the forceful massage affected the endothelial lining of the initial lymphatics. Alterations of lymphatic collectors were visible later. The fluid in lymphedema was translocated by massage using high pressure from the interstitium into the lumen of lymphatics by means of the open junctions and by artificial cracks that develop from injury to the lymphatic wall. Vigorous massage in lymphedema also produces loosening of subcutaneous connective tissue, formation of large tissue channels and release of lipid droplets that enter the lymphatics. By this mechanism, massage helps reduce the amount of fat cells in the lymphedematous leg. PMID- 7791373 TI - The three Williams--Hunter, Hewson and Cruikshank: their unique contributions to our knowledge of the lymphatics. PMID- 7791374 TI - The lymphatic vessels and their relationship to lymph formation in the human urinary bladder. AB - After endoscopic transurethral biopsies of normal human urinary bladder, an extensive network of small initial lymphatic vessels was depicted by means of light and electron microscopy. Using light microscopy, lymphatic vessels were seen in the mucosa and submucosa and formed a complex network in the detrusor muscular coat. These lymphatics were characterized by an irregular and attenuated wall and increased in number and size from the superficial to the deeper region of the bladder. Ultrastructurally, the lymphatic wall was characterized by endothelial cells joined together end-to-end or by complicated interdigitations. Often intercellular channels and gaps between two contiguous endothelial cells were present. A broad network of elastic and collagen fibers joined the lymphatic endothelial wall to the neighboring connective tissue. Nevertheless, as far as the fibrillar component was concerned, the vesical intramuscular lymphatic endothelial wall lacked elastic fibers. These anatomic variations were examined in reference to lymph formation in an organ (the urinary bladder) which undergoes continual changes in volume and pressure. PMID- 7791375 TI - Lymphatic system of the rat pancreas. AB - Light and electron microscopy combined with morphometric analysis were used to investigate the distribution, extent and structure of lymphatic vessels in the head, body and tail of the rat pancreas. Serial sections 3-4 microns in thickness were cut from tissue fixed by perfusion. Alternate sections were processed for light microscopy. Intervening sections were left uncovered to be re-embedded and sectioned for electron microscopy as needed. Vessels with valves were tentatively identified as lymphatics using the light microscope, with final identification being made on adjacent sections by electron microscopy. The ultrastructure of the pancreatic lymphatic vessels was typical of lymphatics generally. Interlobular lymphatic vessels were present throughout the pancreas and were found to be associated primarily with blood vessels lying in connective tissue septa. Intralobular lymphatics were also seen but were comparatively rare. Only about 19% of the wall of the lymphatic system of the pancreas was in close relationship to acinar cells--none was closely related to the endocrine islets. The mean volume density of the system was 0.0012 microns3/microns3 and the profile density of lymphatics was 3.24/mm2. Special attention was paid to the areas of contact between adjacent endothelial cells. Open gaps of more than 30 nm in width were rare. Dilatations and associated cytoplasmic processes, suggestive of a type of intercellular transport, were seen in addition to the intracellular cytoplasmic vesicular system. The findings are consistent with the view that the lymphatic system of the pancreas does not have a specific role in the transport of pancreatic secretions other than the removal of macromolecules that may escape to the interstitium in small amounts under normal circumstances. The fine structure of the endothelial wall suggests that the mechanism of lymph formation in the pancreas is more comparable to that in other encapsulated organs such as the kidney and liver than to that in the dermis or diaphragm where fluid appears to enter lymphatics primarily by way of gaps between adjacent cells. PMID- 7791377 TI - On microwaves. PMID- 7791378 TI - Children's and adolescents' experiences while undergoing cardiac catheterization. AB - PROBLEM: To explore the experiences of children and adolescents undergoing a cardiac catheterization. SUBJECTS: Caucasian children and adolescents (N = 24), 9 17 years, male and female, undergoing cardiac catheterization. METHOD: Exploratory design utilizing content analysis. The authors used an interview guide with 4 subsections to elicit self-reports of knowledge, perceptions, emotions, and evaluations. FINDINGS: Major themes were anticipatory anxiety, pain, invasion of privacy, and being comforted. Many children had misconceptions or lack of knowledge of the procedure. CONCLUSIONS & IMPLICATIONS FOR NURSING: Nurses' knowledge of the impact on children and adolescents of a cardiac catheterization room, high-technology equipment, and invasive procedures may increase their sensitivity to children's and adolescents' perceptions of the experiences and promote individualized nursing care. PMID- 7791376 TI - Measuring peripheral oedema and bioimpedance. PMID- 7791379 TI - Survival from a wild animal attack: a case study analysis of adolescent coping. AB - TOPIC: Adolescent coping strategies and long-term effects of a life-threatening event are examined in this retrospective case study. PURPOSE: To describe the hospital care and follow-up support given to an 11-year-old girl who was savagely mauled by a cougar. An in-depth analysis of the patient's significant memories six-and-a-half years after the incident is also presented. SOURCES: Two hour semi structured, information gathering interviews with the adolescent when she was 16 years old. RESULTS: The outcome of this case study analysis served as a partial debriefing of the experience for the adolescent girl. IMPLICATIONS FOR NURSING PRACTICE: This case study provides a useful resource to practitioners and patients who may experience similar situations. Nurses have a role to play in anticipating and preparing children for later hospital-based, post-trauma interventions and assisting other adolescents who are injured and hospitalized. PMID- 7791381 TI - Biographical update of Dr. William Worrall Mayo. PMID- 7791380 TI - Mothers' moods and social support when a second child is born. AB - PROBLEM: The relationship between mothers' different mood states and dimensions of support; the influence of antepartum and postpartum support on mood states as a function of stress and time. SUBJECTS: Married mothers (N = 50) expecting a second child when their firstborn was between 28-54 months old; 90% Caucasian; ages 24-40 years. Average education: 13 years. METHOD: A short-term longitudinal correlational study to determine second-time mothers' moods relative to dimensions of support, stress, and timing of support. Instruments used: Profile of Mood States, Norbeck Social Support Questionnaire, Situation-Specific Support Scale, and the Crockenberg Stress Checklist. FINDINGS: Depressed, angry, and/or tired mothers reported inappropriate amounts of support and dissatisfaction with support received. CONCLUSIONS & IMPLICATIONS FOR NURSING: Different types of support serve different functions before and after birth. Support must "fit" mothers' needs and is most effective if given when needed because of the limited "carry over" effect. Listening carefully to mothers describe their feelings enables nurses to determine support wanted or needed. PMID- 7791382 TI - Prospective evaluation of clinical characteristics of orthostatic hypotension. AB - OBJECTIVE: To undertake a prospective study of the clinical characteristics of orthostatic intolerant patients referred to the Mayo Autonomic Reflex Laboratory with suspected orthostatic hypotension (OH). DESIGN: Autonomic function tests were performed to quantify the severity of sudomotor, adrenergic, and cardiovagal failure and generate a composite autonomic symptom score (CASS). CASS was related to a symptom score, which was derived from the frequency of orthostatic intolerance and syncope and the standing time until occurrence of symptoms. RESULTS: Three groups were defined by their response to a tilt study: group I, 90 patients with symptomatic OH, mean age, 63.6 years; group II, 60 patients who had symptoms without OH, mean age, 48.9 years; and group III, 5 patients with asymptomatic OH, mean age, 68.0 years. Group I had a significantly higher CASS (P < 0.001) than did those without OH. Further analysis was done on the 90 patients in group I. The most common symptoms were lightheadedness, weakness, impaired cognition, visual blurring, tremulousness, and vertigo. The most common aggravating factors were prolonged standing, exercise, warming, and eating. Most patients (75%) could stand for less than 5 minutes before symptoms occurred. Symptoms regressed significantly with CASS but not with the tilt grade. CONCLUSION: Patients with generalized autonomic failure have a recognizable pattern of symptoms and aggravating factors that relate, albeit imperfectly, to the severity of autonomic failure. PMID- 7791384 TI - Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. AB - OBJECTIVE: To assess the incidence and natural history of alopecia areata (AA) among unselected patients from a community. DESIGN: We conducted a retrospective population-based descriptive study of AA among residents of Olmsted County, Minnesota, for the period from 1975 through 1989. MATERIAL AND METHODS: After identifying 292 Olmsted County residents first diagnosed with AA during the 15 year study period, we reviewed their complete (inpatient and outpatient) medical records in the community and statistically analyzed the effects of gender and age group. RESULTS: The overall incidence of AA was 20.2 per 100,000 person-years and did not change with time. Rates were similar in the two genders and over all ages, and lifetime risk was estimated at 1.7%. Eighty-seven percent of patients were examined by a dermatologist who diagnosed AA, and 29% of cases were confirmed by biopsy. Most patients had mild or moderate disease, but alopecia totalis or universalis developed at some point during the clinical course in 21 patients. CONCLUSION: This study of the incidence and natural history of AA in a community shows that this disorder is fairly common and can be seen at all ages. Although spontaneous resolution is expected in most patients, a small but significant proportion of cases (probably approximately 7%) may evolve into severe and chronic hair loss, which may be psychosocially devastating for affected persons. PMID- 7791383 TI - Nimodipine as an add-on therapy for intractable epilepsy. AB - OBJECTIVE: To analyze the effect of nimodipine in patients with intractable epilepsy. DESIGN: We conducted a double-blind placebo-controlled crossover study in 95 patients. MATERIAL AND METHODS: The dihydropyridine calcium antagonist nimodipine was used as add-on therapy (60 mg four times a day) in a 1-year placebo-controlled crossover study in 71 patients with localization-related epilepsy and 24 with generalized seizure disorders. Of the 95 patients, 81 were receiving two or more antiepileptic drugs. Patients diaries were used to record the number of seizures and any side effects. RESULTS: Nimodipine seemed to be well tolerated during the study; only two patients were unable to complete the study because of probable adverse effects. The trial demonstrated no significant crossover effect and no significant effect of nimodipine on either the mean or the median number of seizures or seizure days. The peak median serum nimodipine level was less than 5 ng/mL in the 78 patients who completed the study. CONCLUSION: This clinical trial found no beneficial effect with use of nimodipine as add-on therapy for intractable epilepsy. Potential reasons for the absence of efficacy of nimodipine may be the inclusion of patients with very refractory seizure disorders or the relatively low serum nimodipine concentrations related to the pharmacokinetic effect of concurrent antiepileptic medication. PMID- 7791385 TI - Idiopathic restrictive cardiomyopathy in childhood: diagnostic features and clinical course. AB - OBJECTIVE: To describe the clinical course and outcome of children with idiopathic restrictive cardiomyopathy (IRCM) and to present the Doppler echocardiographic features of this disease in childhood. DESIGN: We reviewed the Mayo Clinic patient database for the period from 1975 to 1993 to identify children who underwent assessment for IRCM. MATERIAL AND METHODS: Clinical records and diagnostic studies, including two-dimensional (2-D), M-mode, and Doppler echocardiograms, were reviewed for each patient. Characteristics were analyzed statistically to determine potential predictors of outcome. RESULTS: Eight children (five girls and three boys) were diagnosed with IRCM between 1975 and 1993 at our institution. The median age at diagnosis was 11 years, and the median duration of follow-up was 11.5 years. Of the eight patients, five died (the median time from initial examination to death was 1 year). All five of these patients had clinical and radiographic evidence of pulmonary venous congestion. In all patients, 2-D and M-mode echocardiography revealed atrial enlargement without ventricular dilatation or hypertrophy. The four patients who underwent detailed diastolic Doppler assessment had findings consistent with restrictive filling and increased left ventricular end-diastolic pressure: (1) short mitral deceleration time, (2) increased pulmonary vein atrial reversal velocity and duration, and (3) pulmonary vein atrial reversal duration greater than mitral A wave duration. CONCLUSION: The prognosis for children with IRCM is poor. In this small group of patients, absence of pulmonary venous congestion most consistently predicted extended survival. A combined 2-D and Doppler echocardiographic examination provides a reliable noninvasive means of assessing the physiologic and morphologic features of IRCM in children. PMID- 7791386 TI - Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex. AB - OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction. PMID- 7791387 TI - Home peak expiratory flow rate monitoring in patients with asthma. AB - OBJECTIVE: To describe how the peak expiratory flow rate (PEFR) is measured, review published studies of the accuracy in which patients and physicians can estimate the severity of asthma by clinical observations only, and review published studies of the benefits of home PEFR monitoring. DESIGN: A review of home PEFR monitoring and its associated benefits for both the physician and the patient is presented. RESULTS: An accurate assessment of the severity of asthma is crucial for the optimal treatment of the patient with asthma; however, patients and their physicians are often unable to estimate correctly the degree of airway obstruction. Peak flow measurement is a simple, inexpensive method of objectively determining airflow obstruction. Management of asthma based on home PEFR measurements can result in early recognition and prompt treatment of asthma exacerbations. Home PEFR monitoring in the setting of a comprehensive self management program can lead to fewer symptoms of asthma, fewer days absent from work or school, fewer emergency examinations, fewer hospitalizations, lower requirements of inhaled beta-antagonists and oral corticosteroid therapy, and better pulmonary function. CONCLUSION: For best results, home PEFR monitoring should be coupled with a thorough educational program on asthma and periodic office spirometry. PMID- 7791388 TI - Cardiac echinococcosis: case report of unusual echocardiographic appearance. AB - An unusual echocardiographic appearance of a cardiac echinococcal lesion confirmed intraoperatively is described in a patient with nonspecific cardiac complaints. Although previous reports have emphasized the echolucent, often multiseptated nature of echinococcal lesions, such characteristics were absent in this case. Thus, in the appropriate clinical setting, echinococcal infection should be included in the differential diagnosis of solid mass lesions of the heart because the surgical approach may need to be altered. PMID- 7791389 TI - Chronic cough associated with subacute bacterial endocarditis. AB - Although the literature on subacute bacterial endocarditis from both the preantibiotic and antibiotic eras mentions cough as a symptom, neither bacteremia nor endocarditis is listed in reviews on chronic cough. Herein we describe a 74 year-old man who underwent an extensive workup as an outpatient because of chronic cough of 7 months' duration. Chest roentgenography, chest and sinus computed tomography, fiberoptic bronchoscopy, gallium scan, transthoracic echocardiography, and other studies revealed no apparent cause for his nonproductive cough. Because of a persistently increased erythrocyte sedimentation rate and associated weight loss, blood cultures were obtained, all of which grew Streptococcus constellatus. A transesophageal echocardiogram revealed mitral valve vegetation. After antibiotic therapy was administered, the patient's cough completely resolved. He has experienced no coughing for more than 14 months. Bacteremia in conjunction with endocarditis should be added to the list of uncommon causes of chronic cough. The mechanism of cough is unknown. PMID- 7791390 TI - Lymphoma associated with human immunodeficiency virus infection. AB - OBJECTIVE: To describe lymphoma associated with human immunodeficiency virus (HIV) infection. DESIGN: A review of HIV-related lymphoma and its associated epidemiology, etiopathogenesis, and clinicopathologic characteristics is presented. Major studies of therapeutic regimens for HIV-related lymphoma are discussed. Factors that could contribute to a poor prognosis are summarized. RESULTS: Malignant lymphoma that develops in patients with HIV infection fulfills diagnostic criteria for the acquired immunodeficiency syndrome (AIDS). The incidence is increasing and varies by subtype of lymphoma, age, sex, race, and risk factors. B-cell hyperactivation is thought to contribute to the development of lymphoma. The mechanisms that may show transformed cell hyperproliferation and clonal expansion are HIV itself or other viruses (for example, Epstein-Barr virus), growth factors, aberrant oncogene or tumor-suppressor gene expression, and factors that induce genetic instability or DNA damage or alter host or viral genome repair. Treatment of HIV-related lymphoma is associated with toxicity, infectious complications, low rate of complete response, and brief median survival time. CONCLUSION: Persons with HIV-induced immune dysregulation have a high risk for the development of aggressive non-Hodgkin's lymphoma characterized by histologic evidence of a high-grade malignant process, B-cell phenotype, an unusual extranodal involvement, and a poor prognosis. The potential role of specific viruses, antiviral treatments, and other therapeutic strategies are future areas of investigation. PMID- 7791391 TI - Myelodysplastic (preleukemia) syndromes: the bone marrow factory failure problem. AB - The myelodysplastic syndromes are a group of hematologic disorders that adversely affect the levels of hemoglobin, platelets, erythrocytes, and leukocytes. Although the cause of this syndrome is unknown, new diagnostic techniques have facilitated identification and classification of these diseases into five categories: refractory anemia (refractory cytopenia), refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Cytogenetic abnormalities may be present in more than 55% of the patients. Symptomatic patients should be assessed relative to life-threatening versus non-life threatening cytopenias and age. Management consists of primarily supportive measures, although certain approaches that are currently being used or under investigation, such as concomitant administration of erythropoietin and other growth factors, show promise for the future. PMID- 7791393 TI - Virginia Apgar--the Apgar score. PMID- 7791392 TI - Prognostic factors for patients with carcinoma of the breast. PMID- 7791394 TI - Symposium on geriatrics. Foreword. PMID- 7791395 TI - Symposium on geriatrics. Introduction. PMID- 7791396 TI - Symposium on geriatrics--Part I: Drug prescribing for elderly patients. AB - OBJECTIVE: To describe the pharmacokinetic and pharmacodynamic changes that occur with aging and to discuss common problems noted with the use of medications often prescribed for elderly patients. DESIGN: We searched the medical literature, reviewed pertinent articles, and summarized drug-related information applicable to geriatric patients. RESULTS: Use of medications is common in the elderly population; most elderly persons take two or more different medications each day. Aging is associated with anatomic and physiologic changes that can have an effect on how medications are handled. Such changes include alterations in various volumes of drug distribution and in drug absorption, metabolism, and clearance. Elderly patients may also have increased or decreased drug effects because of alteration in receptor response. These changes in pharmacokinetics and pharmacodynamics may result in a prolonged drug half-life, an increased potential for drug toxicity, and a greater likelihood for adverse drug reactions. CONCLUSION: Medications for elderly patients should be prescribed only after the anatomic and physiologic changes of aging are understood and with increased surveillance for potential drug toxicity or adverse drug reactions. PMID- 7791397 TI - Medical care of nursing home residents. AB - OBJECTIVE: To present an overview of the special challenges of providing medical care for nursing home residents. DESIGN: After researching the current medical literature, we summarized information on nursing home demographics, government regulations, and specific care issues for medical practice in nursing homes. RESULTS: Almost 2 million Americans currently live in more than 20,000 nursing homes nationwide, and these nursing home residents are increasingly older and more frail than in the past. Most nursing home residents receive multiple prescription medications, and many are cognitively and functionally impaired. Nursing home-acquired infections are a frequent occurrence, as are falls and fall related injuries. Recent federal laws have had a major effect on medical care in the nursing home and have made physicians more accountable for the care provided. The use of physical restraints and psychotropic drugs has been severely restricted. CONCLUSION: The medical care of nursing home residents presents many challenges to primary-care physicians. Nevertheless, nursing home residents are among those patients in greatest need of competent, compassionate care. Despite numerous disincentives, provision of medical care for nursing home residents can be gratifying. PMID- 7791398 TI - 64-year-old man with polyuria and polydipsia. PMID- 7791399 TI - Randomized clinical trails: potential cost savings due to the identification of ineffective medical therapies. PMID- 7791400 TI - Variations in the clinical manifestations of orthostatic hypotension. PMID- 7791402 TI - Additional causes of the blue toe syndrome. PMID- 7791401 TI - Calcium antagonists and epilepsy. PMID- 7791403 TI - Molecular and cell biological studies of ageing and their application to considerations of T lymphocyte immunosenescence. PMID- 7791405 TI - [Involvement of histocompatibility and allosensitization in recurrent abortions]. AB - BACKGROUND: The aim of this study was to know the possible implication of human histocompatibility (HLA) antigens in the etiology of repeated abortions. METHODS: Antigen typing for the major histocompatibility system was carried out in 65 couples with 2 or more abortions and comparative analysis was performed with 40 fertile couples by the odds ratio. Likewise, the possible relationship between cytotoxic antibodies in maternal serum and reproductive prognosis was determined. RESULTS: The couples with abortions did not present a significantly different phenotypic frequency from that of the fertile couples in regard to the HLA antigens (loci HLA-A, HLA-B, and HLA-DR). On considering the 3 loci studied, the infertile couples presented significantly higher antigenic HLA identity than the fertile couples. This significance was demonstrable both by association and by odds ratio (OR: 4.9; CI 95%; 1.1-9.2). No differences were observed among women with primary (no full term pregnancy) or secondary abortions (some full term pregnancies) with regard to common HLA antigens, with both groups being homogeneous. CONCLUSIONS: The presence of cytotoxic antibodies against paternal lymphocytes in maternal serum detected by cross-match reaction was not related to the pertaining to an infertile (including any of the established subgroups) or fertile population. Neither were differences observed in the presence of these antibodies among women with primary or secondary abortions. PMID- 7791404 TI - Ultrastructural differences of hippocampal lipofuscin in human development. AB - The lipofuscin of pyramidal cells in each hippocampal subfield of each of seven human autopsy cases without brain disease at the age of 3-12 months (infants) and of 17-23 years (young adults) was comparatively investigated at the electron microscopic level. In infant pyramidal neurons of the hippocampal subfields CA 1, CA 2, CA 3 and CA 4 O-2, very small lipofuscin particles were observed. The lipofuscin composition showed a slightly larger granular component compared to the vacuolar component with one or two small lipid droplets. No obvious ultrastructural variability of lipofuscin granules was observed. The CA 1 lipofuscin in young adults consists of larger particles than in infants, but no obvious difference in the composition of granular and vacuolar components from the infant lipofuscin was seen. The amount of lipofuscin in CA 1 strongly increased in young adults compared to infants and appeared in a perinuclear distribution. In young adults, in contrast to the infant group, the amount of lipofuscin in the subfields CA 2, CA 3 and CA 4 was significantly higher than in CA 1. In CA 2, CA 3 and CA 4 pyramidal neurons, the vacuolar component was significantly larger than the granular component. The similarity of infant hippocampal lipofuscin patterns in all subfields is discussed as a state of immaturity. To explain the observed differences between the CA 1 and the other subfields during neuronal development, as shown in the young adult group, several factors are discussed: the effects of cell specific metabolism, cellular functional activity, cytoprotective mechanisms and effects of efferent and afferent pathways connected with the subfields. PMID- 7791407 TI - [Electrocardiographic patterns in hypertensive patients without atherosclerotic coronary disease. Influence of the left ventricular mass]. AB - BACKGROUND: ECG ST-T segment abnormalities in hypertensive patients are traditionally associated with hypertrophy or ischaemia. Hypertensive patients with abnormalities in ST-T segment in DI, aVL and/or V5-V6 underwent an echocardiographic study in order to assess left ventricular structure. All of them, in addition to the electric changes, showed typical or non-typical thoracic discomfort, showing a normal coronariographic study. METHODS: Hypertensive patients with ST-T segment changes were classified as follows: group A, 12 patients (8 women, 4 men, mean age 63.6 +/- 7.2 years) with ECG image of left ventricular overload pattern; group B, 9 patients (3 men, 6 women, mean age 62.3 +/- 6.3 years) with flat ST segment depression; and group C, 10 patients (3 men, 7 women, mean age 62.4 +/- 9.7 years) without changes on the ST-T segment with flat or negative T wave. Control group is made up 12 hypertensive patients (7 women, 5 men, mean age 61.6 +/- 7.6 years) with normal ECG. We assess by echocardiography interventricular septal thickness (IVST) and left ventricular posterior wall thickness (PWT) in mm, left ventricular end-diastolic diameter (DTD) in mm, left ventricular mass (LVM) in grs, and the mass index (MI) in g/m2. RESULTS: IVST, PWT, LVM and MI were significantly (p < 0.05) higher in the groups A, B and C than in the control group. No statistically significant differences were observed between the A, B and C groups. Stepwise discriminant analysis showed that the only parameter with independent value for discriminating between control, group and group ABC (the union of groups A, B and C) was IVST. CONCLUSION: In hypertensive patients without coronariopathy, ST-T changes identify a group with greater left ventricular mass. The different electrocardiographic patterns considered were not associated with a significantly different left ventricular mass. PMID- 7791406 TI - [IgG subclasses in patients with symptomatic IgA deficiency]. AB - BACKGROUND: Patients with IgA deficiency may be asymptomatic or may present recurrent infections mainly respiratory. A possible explanation for this variety of symptoms may be the association with a deficiency of IgG subclasses. METHODS: Twenty-five patients with a symptomatic IgA deficiency with a mean age of 18 +/- 12 years were studied. The quantification of the IgG subclasses was performed by ELISA test with antisubclass specific monoclonal murine antibodies. Serum from 100 healthy adults was collected to determine normal values of the IgG subclasses. RESULTS: Twenty-five (48%) had a deficiency of associated IgG subclasses (6 IgG2 deficiency, 1 IgG3, 3 IgG4 and 2 combined deficiency). The patient with a deficiency of associated IgG subclasses had more recurrent respiratory infections (chi 2, p < 0.03) and pneumonias (chi 2, p < 0.04). This group also had a greater FEV1 alteration (Student-t test, p < 0.04). CONCLUSIONS: Patients with symptomatic IgA deficiency frequently present IgG subclass deficiency and are more likely to have recurrent respiratory infections and greater changes in pulmonary function. PMID- 7791408 TI - [Recurrent abortion: genetic and acquired factors]. PMID- 7791409 TI - [Celerius, profundius, periculosius]. PMID- 7791410 TI - [Dysbaric accident in deep sea fishing]. AB - The case of a dysbaric accident with occurred in a professional athlete during a national competition is herein reported. The clinical symptoms and response to treatment in a depressurization chamber in addition to CT controls should alert physicians in coastal areas in which this sport is carried out in order to take into consideration neurologic disorders which may be due to dysbaric accidents such as those which occur in scuba divers. PMID- 7791411 TI - [Internet in medicine of the year 2000]. PMID- 7791412 TI - [Formulation of a non-related anonymous screening program for HIV]. PMID- 7791413 TI - [Clinical pharmacologists and clinical research ethics committees]. PMID- 7791415 TI - [Professional asthenia syndrome, data relevance, and statistical totem]. PMID- 7791414 TI - [Prenatal diagnosis of HIV infection]. PMID- 7791416 TI - Antipseudomonal penicillins. AB - Antipseudomonal penicillins retain most of the antibacterial activity of penicillin and aminopenicillins. This group of penicillins has added activities against many gram-negative rods, including P. aeruginosa. Similar to the earlier penicillins, this group continues to be susceptible to hydrolysis by many beta lactamases and are, therefore, not consistently active against Staphylococcus, some gram-negative rods, and certain beta-lactamase-producing gram-negative anaerobes. The ureidopenicillins, especially piperacillin, appear to have better activity against Enterococcus, Klebsiella, and P. aeruginosa than ticarcillin. The advantages over the newer cephalosporins are (1) better activity against Enterococcus, (2) more consistent activity against Clostridium, and (3) more consistent synergy with aminoglycosides. The ureidopenicillins have certain advantages over carboxypenicillins, including lower sodium load, less frequent hypokalemia, reduced platelet dysfunction, minimal dosage adjustment in patients with renal failure, and a wider spectrum of antibacterial activity, especially against Enterococcus, Pseudomonas, and Klebsiella. The utility of the antipseudomonal penicillins by themselves is limited as agents for monotherapy when the infecting organism is not known. In addition, monotherapy is not recommended in certain infections to avoid the development of resistance. When combined with a beta-lactamase inhibitor or with an aminoglycoside, however, some of the weaknesses can be overcome. PMID- 7791417 TI - Beta-lactamase inhibitor combinations. AB - The beta-lactamase inhibitor combinations present a novel approach to the problem of beta-lactamase-induced resistance to antibiotics. These agents are derived from the generally safe beta-lactam class of antibiotics. They are all principally excreted through the kidneys and require dosage adjustment in the face of significant renal insufficiency. They show significantly increased activity against methicillin-sensitive S. aureus, H. influenzae, B. catarrhalis, and B. fragilis. The activity against Enterococcus, Pseudomonas, and most gram negative bacilli, however, remains limited to that of the respective antibiotic component. Although shown to be clinically useful in a variety of clinical situations, they appear to be most useful for skin and soft tissue infections and lower respiratory tract infections as well as intra-abdominal and gynecologic infections caused by susceptible pathogens. PMID- 7791418 TI - Third-generation cephalosporins. AB - Third-generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations. No one cephalosporin is appropriate for all infectious disease problems. Cefotaxime and ceftizoxime have the best gram positive coverage of the third-generation agents. Ceftazidime and cefoperazone are the only third-generation drugs that provide antipseudomonal coverage. Ceftriaxone's long half-life allows for once-daily dosing, making ceftriaxone an excellent drug for outpatient antibiotic therapy of community-acquired infections. Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases. The third-generation cephalosporins except for cefoperazone penetrate cerebrospinal fluid and are indicated for the treatment of bacterial meningitis. Their proven record of clinical efficacy, favorable pharmacokinetics, and low frequency of adverse effects make third-generation cephalosporins the preferred antibiotic in many clinical situations. PMID- 7791419 TI - Cefepime. AB - Because of the popularity of some third-generation cephalosporins, emergence of resistant organisms (e.g., selected Enterobacteriaceae) that produce inducible and extended-spectrum beta-lactamases has been a problem. Cefepime's twice-a-day dosage schedule and enhanced activity against Enterobacteriaceae and gram positive organisms give it several advantages over older drugs. The clinical efficacy of cefepime has been demonstrated in comparative and noncomparative trials in the United States and Europe. Cefepime with twice-daily dosing has been useful in the treatment of lower respiratory tract infections, urinary tract infections, skin and skin structure infections, and in serious infection, including those with associated bacteremia. Cefepime is comparable to ceftazidime in clinical and bacteriologic response rates when both agents are administered three times a day in febrile neutropenic patients. Cefepime is also active against organisms that show resistance to other agents. Several studies have shown that cefepime retains its activity against E. cloacae and E. coli strains resistant to other cephalosporins and against many strains of P. aeruginosa resistant to ceftazidime. Cefepime exhibits a low level of cross-resistance with third-generation cephalosporins and a low propensity for selection of resistant mutants and offers a low potential for the induction of bacterial resistance, which complicates the course of many patients treated with single-agent third generation therapy. Cefepime should be used in place of ceftazidime based on resistance potential, activity against resistant organisms, and cost. PMID- 7791420 TI - Aztreonam. AB - Aztreonam is a monocyclic beta-lactam antibiotic that is active exclusively against the aerobic gram-negative bacilli. It is not ototoxic or nephrotoxic and so is used as an alternative to aminoglycosides in a variety of clinical situations. In polymicrobial infections or when used for empiric therapy, aztreonam must be combined with other antimicrobial agents active against gram positive and anaerobic species. Aztreonam is often effective against resistant strains of gram-negative organisms, which are often involved in nosocomial infections. Overuse of aztreonam should be avoided to prevent the emergence of resistant P. aeruginosa strains. Except in the treatment of P. aeruginosa infections, aztreonam should not be added to beta-lactam regimens for additional gram-negative coverage. PMID- 7791421 TI - Carbapenems. AB - Carbapenems are broad-spectrum beta-lactam antibiotics that cover an absolute majority of all bacterial pathogens that possess a cell wall. The only clinically important exceptions are X. maltophilia, E. faecium, and some strains of methicillin-resistant staphylococci and penicillin-resistant pneumococci. So far, after several years of clinical use of imipenemcilastatin, emergence of resistance has been a problem mainly restricted to P. aeruginosa. The pharmacokinetics of carbapenems, especially imipenem, are complicated by the renal metabolism, necessitating the imipenem-cilastatin combination. This is not required for meropenem. The safety profile of carbapenems is favorable. With imipenem-cilastatin, nausea constitutes a practical problem in that administration times may have to be prolonged. The risk for neurologic reactions with imipenem-cilastatin has become a factor reducing the possibilities to use high doses. For all indications except bacterial meningitis, the now approved maximal dose of 4 g per day should suffice. In this respect, meropenem has an advantage over imipenem-cilastatin in that it can be used in the treatment of bacterial meningitis without apparent increased risk of seizures. Carbapenems are indicated mainly as empiric monotherapy in serious infections, such as intra abdominal infections and infections in neutropenic patients. Combinations of carbapenems and other antibiotics should not be used routinely. PMID- 7791422 TI - Aminoglycosides. AB - Despite their nephrotoxic and ototoxic side effects, AG remain useful antibiotics because of their major, rapid, and dose-dependent bactericidal effects. Combination therapy with an AG appears particularly important in neutropenic and other high-risk patients to provide broad-spectrum bactericidal activity, synergism, and reduction of emergence of resistant pathogens. OD AG therapy is associated with high peak levels in serum that maintain efficacy and low-to undetectable trough levels in serum that attenuate the risk of toxicity. Administration of short-term OD AG therapy to patients not at risk without renal impairment may not absolutely require dosing monitoring. This therapeutic strategy has been proved useful in clinical trials, now including febrile episodes in neutropenic patients, but it should be avoided during infections in which antimicrobial synergism is required, such as enterococcal endocarditis. PMID- 7791424 TI - Azithromycin and clarithromycin. AB - Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections. In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient. This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once daily dosing to 58% with four-times-a-day dosing. Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous. In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H. influenzae, MAC in AIDS, MOTT, and leprosy. Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis. PMID- 7791423 TI - Tetracyclines. AB - Tetracyclines are relatively safe drugs with a broad antimicrobial spectrum. Doxycycline remains the preferred tetracycline agent for most indications. Doxycycline has a long half-life, which makes convenient twice-a-day dosing possible. It is well absorbed orally even in the presence of food, has excellent tissue penetration, and does not require a dose adjustment in renal insufficiency. Doxycycline is a useful agent for the treatment of atypical pneumonias, sexually transmitted diseases, traveler's diarrhea, rickettsial infections, and Lyme disease. Minocycline is the preferred drug for MRSA colonization/infection. PMID- 7791425 TI - Vancomycin. AB - Vancomycin is a nontoxic glycopeptide antibiotic most often used to treat serious gram-positive infections, C. difficile diarrhea/colitis, and endocarditis and hemodialysis shunt prophylaxis. Vancomycin should not be added to drug regimens for gram-positive coverage, and the empiric use of vancomycin should be discouraged to avoid the emergence of VRE. Vancomycin serum levels are no longer necessary or cost effective in most patients because vancomycin is not nephrotoxic. PMID- 7791426 TI - Teicoplanin. AB - Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, has proved effective in the treatment of various gram-positive infections in both the normal and the immunocompromised host. In vitro activity against most gram-positive organisms is equal to or greater than that of vancomycin. In both open and comparative clinical trials, teicoplanin has been well tolerated, rarely prompting discontinuation of treatment. Nephrotoxicity caused by teicoplanin is uncommon, even when used concomitantly with aminoglycosides or cyclosporin A. Favorable pharmacokinetics allow for intramuscular administration as well as intravenous bolus dosing, and, after appropriate loading doses, maintenance therapy may be given on a once-daily basis. The combination of all of these factors makes teicoplanin an effective, safe alternative to vancomycin in the treatment of gram-positive infections. PMID- 7791427 TI - Clindamycin and metronidazole. AB - Metronidazole is a bactericidal antibiotic with strong activity against most anaerobes and certain parasites. The drug has excellent bioavailability and good penetration in most tissues, including the cerebrospinal fluid and brain abscess contents. It is usually well tolerated with few side effects. With a few exceptions, the percentage of anaerobes, including B. fragilis group, that are resistant to metronidazole remains low. Metronidazole has been used extensively in clinical practice for years, and its uses have expanded. Its exact role in the management of Crohn's disease and entities related to H. pylori is evolving. PMID- 7791428 TI - Quinolones. AB - Fluoroquinolones represent a major advance in antimicrobial chemotherapy. Currently, there are five fluoroquinolones approved by the FDA, and many more quinolones are expected to become available in years to come. Although their clinical utility is constantly expanding, they have been best studied in complicated urinary tract infections, chronic osteomyelitis caused by gram negative bacilli, bacterial gastrointestinal infections such as traveler's diarrhea and typhoid fever, and uncomplicated gonococcal infections and in the prophylaxis of bacterial infections in patients with neutropenia. These agents have the convenience of oral administration, favorable pharmacokinetic properties, and low toxicity profiles but should be used advisedly because indiscriminate use may result in the early emergence of resistance. PMID- 7791429 TI - Anti-infective agents and hepatic disease. AB - Numerous factors such as changes in plasma protein binding, tissue binding, hepatic blood flow, hepatic metabolism, and distribution may occur in hepatic disease. The impact of these physiologic changes on pharmacokinetic and pharmacodynamic parameters of anti-infective agents is likely to be clinically significant. Unfortunately, these issues have not been thoroughly investigated. Even within the same type of liver disease, there is considerable interpatient variability in pharmacokinetic variables, rendering it difficult to predict drug disposition accurately. Pharmacokinetics of selected anti-infective agents are altered in hepatic disease, necessitating careful monitoring and dosage titration to avoid enhanced drug concentrations and risk of toxicity. PMID- 7791430 TI - Antibiotic dosing in renal failure. AB - The Dosing in Renopathy by Easy-To-Use Multipliers (DREM) System is a simple method for dose adjustments of anti-infectives in renal insufficiency. The simple 2-step method involves: (1) estimating creatinine clearance (CLcr) from age, sex, and serum creatinine, and (2) calculating the adjusted dose or dosing interval with the use of multipliers. By multiplying the normal dose or dosing interval with the dose (CLcr/100) or interval (100'CLcr) multiplier, the adjusted dose or dosing interval is obtained, respectively. Dose estimates with this method are reasonably accurate and compare favorably with previously published methods of correction. PMID- 7791431 TI - Antibiotic therapy in the allergic patient. AB - A variety of antimicrobial classes are now available. Thus, a careful history and skin testing for hypersensitivity reactions are often not done. It is often easier to give an alternative agent rather than to determine if the person does indeed have a hypersensitivity reaction to a particular drug. There remain situations (e.g., enterococcal endocarditis, neurosyphilis, syphilis in pregnant women), however, in which options for appropriate therapy are limited. In this setting, an accurate history accompanied by appropriate skin testing and desensitization is indicated. PMID- 7791432 TI - Death by denial. PMID- 7791433 TI - Glucose and the metabolism of ischaemic myocardium. PMID- 7791434 TI - New classification for lymphomas. PMID- 7791435 TI - Groin strain versus occult hernia: uncomfortable alternatives or incompatible rivals? PMID- 7791436 TI - Coronary artery stents. PMID- 7791437 TI - Long-term sequelae of Helicobacter pylori gastritis. AB - Chronic Helicobacter pylori gastritis has been put forward as a risk factor for development of gastric mucosal atrophy and gastric cancer. The purpose of our study was to investigate the long-term effects of H pylori gastritis on the gastric mucosa. We prospectively studied 49 subjects negative for H pylori and 58 positive subjects for a mean follow-up of 11.5 years (range 10-13 years). Serum samples were obtained at the initial and follow-up visits for determination of H pylori IgG antibodies. Gastroscopies with biopsy sampling were done in all patients at both visits. Biopsy specimens were used for assessment of H pylori infection and histology. Development of atrophic gastritis and intestinal metaplasia occurred in 2 (4%) uninfected and 16 (28%) infected subjects. Regression of atrophy was noted in 4 (7%) infected subjects. Development of atrophic gastritis and intestinal metaplasia was significantly associated with H pylori infection (p = 0.0014; odds ratio 9.0, 95% CI 1.9-41.3). The proportion of atrophic gastritis in the study population showed an annual increase of 1.15% (0.5-1.8%). We conclude that H pylori infection is a significant risk factor for development of atrophic gastritis and intestinal metaplasia. Our findings support strongly the causative role of this infection in gastric carcinogenesis. PMID- 7791438 TI - Human papillomavirus testing in primary cervical screening. AB - Several studies have examined the role of tests for human papillomavirus (HPV) in screening for cervical cancer but as yet the relevance is unclear. We looked at HPV testing for types 16, 18, 31, and 33 on material taken at the time of a cervical smear in 2009 eligible women having routine screening. Women with any degree of dyskaryosis or high levels of one of these HPV types were referred for colposcopy. 44% of the cervical intraepithelial neoplasia (CIN) lesions of grade 2/3 detected had negative cytology and were found only by HPV testing. A further 22% of the CIN 2/3 lesions were positive for HPV but showed only borderline or mild cytological changes. The positive predictive value of HPV testing was 42%, which was similar to that for moderate dyskaryosis. HPV types 16 and 31 were more sensitive and specific for CIN 2/3 than were types 18 or 33. However, 25% of the CIN 2/3 lesions were not detected by these four HPV tests. We suggest that HPV testing could usefully augment but not replace conventional cytology. These results should stimulate a much larger randomised trial to assess the impact of these improved CIN 2/3 detection rates on the subsequent incidence of invasive cancer. PMID- 7791439 TI - Is extrinsic sugar a vehicle for dietary fat? AB - Although many guidelines to healthy eating recommend restriction of the intake of extrinsic (refined) sugar, there are concerns that such restriction might result in an increase in the amount and the proportion of dietary fats with a consequent possible increase in the risk of cardiovascular disease. We used regression analysis to examine the determinants of fat intake in subjects from a population survey who had weighed their food for 4 days. In men (n = 77) and women (n = 83), fat eaten was positively related to the intake of extrinsic sugar. When intakes were expressed as percent of calories the relation became negative. A survey in a semi-random sample of 739 men aged 40-69 yr and 976 women aged 25-69 yr showed that, in both sexes, an increase in extrinsic sugar was associated with a linear increase in the intake of sweetened fat and hence of fat combined with carbohydrate. This was due mainly to a higher intake of cakes and biscuits. Foods containing sugar and fat provided an extra 12.0 g per day of fat in the men and 13.8 g per day in the women when the highest quartile of extrinsic sugar consumers were compared with the lowest quartile. We conclude that lowering the intake of extrinsic sugar is unlikely to be associated with higher fat intake. Instead extrinsic sugar may act as a vehicle for fat intake, encouraging consumption by making the fat more palatable. PMID- 7791440 TI - Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy. AB - We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy. PMID- 7791442 TI - Falls, a community care perspective. PMID- 7791441 TI - HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies. AB - The spondyloarthropathies are associated by an unknown mechanism with HLA-B27 and certain bacteria. HLA-B27 shares sequence with proteins from enteric bacteria. The B*2705 sequence contains a nonapeptide, LRRYLENGK, predicted to bind in the binding cleft of B27. Some nonapeptides from enteric organisms that share sequence with this nonapeptide of B27 also bind B27. These observations suggest an unappreciated mechanism for autoimmunity that may operate in the B27 associated spondyloarthropathies involving peptides bound to and derived from histocompatibility alleles. PMID- 7791444 TI - Do we need more anti-hypertensive drugs: lessons from the new biology. PMID- 7791443 TI - Metabolic support for the postischaemic heart. PMID- 7791445 TI - Gloomy season for the social sciences. PMID- 7791446 TI - Swedes support UNAIDS. PMID- 7791447 TI - Hantaviruses: the rodents take revenge. PMID- 7791448 TI - Cholera treatment in Goma. PMID- 7791449 TI - Cholera treatment in Goma. PMID- 7791450 TI - Cholera treatment in Goma. PMID- 7791451 TI - Oral rehydration therapy. PMID- 7791452 TI - Formulating apomorphine for Parkinson's disease. PMID- 7791453 TI - Hantavirus antibodies in European mammalogists. PMID- 7791454 TI - Time to consider additional diagnostic criteria for HTLV-I-associated myelopathy? PMID- 7791455 TI - "Tumour suppressor gene" concept of carcinogenesis. PMID- 7791456 TI - Treatment for glioma. PMID- 7791458 TI - Thyrotropin-releasing hormone for prevention of neonatal respiratory disease. PMID- 7791457 TI - Glutathione S-transferase alpha as marker for hepatocellular damage in pre eclampsia and HELLP syndrome. PMID- 7791459 TI - Chronic arterial hypertension as unique symptom of brainstem astrocytoma. PMID- 7791460 TI - Manipulating medicine. PMID- 7791461 TI - Teaching ethics in Japan. PMID- 7791462 TI - Threat to German cancer-screening plan. PMID- 7791463 TI - Infection and hospital laundry. PMID- 7791464 TI - Hepatitis B vaccination follow-up. PMID- 7791465 TI - Hepatitis B vaccine and anti-HBs complex as approach for vaccine therapy. PMID- 7791466 TI - Adverse effects of acupuncture. PMID- 7791467 TI - Denture carriage of methicillin-resistant Staphylococcus aureus. PMID- 7791468 TI - Identical-twin small-bowel transplant for desmoid tumour. PMID- 7791469 TI - Helicobacter pylori: a human pathogen. PMID- 7791472 TI - String test for Helicobacter pylori. PMID- 7791470 TI - Helicobacter pylori: a human pathogen. PMID- 7791471 TI - Helicobacter pylori: a human pathogen. PMID- 7791473 TI - Allergic response to Brunei frog Staurois natator. PMID- 7791475 TI - Fluorouracil and folinic acid in colon cancer. PMID- 7791474 TI - Listeriosis from consumption of raw-milk cheese. PMID- 7791476 TI - Fluorouracil and folinic acid in colon cancer. IMPACT Investigators. PMID- 7791477 TI - Cutaneous T-cell lymphoma and calcitriol and isotretinoin treatment. PMID- 7791478 TI - Bilateral facial palsy and meningitis caused by Borrelia double infection. PMID- 7791479 TI - Pruritus. PMID- 7791480 TI - Pruritus. PMID- 7791481 TI - [Prognostic factors in pancreatic carcinoma]. PMID- 7791482 TI - [Multivariate analysis of prognostic factors after resection of ductal pancreatic carcinomas]. AB - At Hanover Medical School 466 patients were operated for ductal pancreatic cancer from 1971 to 1993. In 192 cases the pancreatic tumor could be resected, which amounts to a resection rate of 41%. These patients were subjected to uni- und multivariate factorial analysis in order to evaluate factors of significant prognostic value. Extended pancreatic resection because of vascular involvement or invasion of adjacent organs was performed in 40% (n = 77) of the cases. A curative R0 resection was possible in 85% of patients. The operative lethality dropped with time and from 1985 to 1993 was 3.5%. Patient survival at 5 years was 13.4% with a median survival time of 10.9 months. According to the univariate analysis the prognosis deteriorated with increasing tumor size and lymphatic and hematogenic metastases. There was a significant correlation between tumor stage according to the UICC and prognosis. The prognosis after resection was also significantly influenced by the residual tumor state and tumor grading. Extended pancreatic resections, however, had no significant prognostic impact. The multivariate analysis showed that only three factors were of independent significant relevance: residual tumor state, tumor size and tumor grade. The presence or absence of lymphatic and hematogenic metastases had no independent prognostic significance after resection of ductal pancreatic carcinomas. PMID- 7791484 TI - Effects of ozone on how well split-thickness skin grafts according to Thiersch take in war wounds. Results of prospective study. AB - In a prospective study on 35 wounded persons we examined the effects of ozone on how well split-thickness skin grafts took in war wounds. Each of the 35 wounded persons hat at least two similar gunshot wounds, one on the lower leg or forearm and the other on the upper leg or upper arm. During the first 10 days all wounds were treated with 10% NaCl water solution dressings until the moment when healthy granulations were observed. Thereafter, the defects were covered with split thickness skin grafts according to Thiersch. For technical reasons we treated grafts on the lower leg and forearm with ozone following the usual scheme. Grafts on the upper leg or upper arm were treated in the conventional way and they served as a control group. The results obtained in the group followed up are presented by percentage of graft takes after 10 days and accordingly compared with the results obtained in the control group. There was a higher percentage of takes in ozone-treated split-thickness skin grafts. More than 74.3% of the split thickness skin grafts treated with ozone had a take of more than 75% of the covered surface as apposed to only 40% of the grafts treated with the conventional method. The results in these two groups were compared with a chi square matched pair test. Difference in take of the skin grafts in these two groups was statistically significant at P < 0.01. PMID- 7791483 TI - [Fournier gangrene]. AB - Fournier's gangrene is a relatively rare, mixed aerobic and anaerobic soft tissue infection in the perineoscrotal area. Although it is convenient to give it a separate name, it is really either necrotizing fasciitis or nonclostridial myonecrosis of the scrotal and perineal areas. The condition frequently develops from perineal diseases, including perianal abscess, and fistulas, inflamed haemorrhoids and indwelling urethral catheter. In patients with Fournier's gangrene morbidity is extreme and mortality high. This article is based on a retrospective study of 15 cases of Fournier's gangrene, 13 in male and 2 in female patients. A combination of surgery and antibiotics was used to treat 9 patients. The last 6 cases were treated with a combination of surgery, antibiotics and hyperbaric oxygen. In 13 cases, the diagnosis was made on the basis of the fulminating progression of the infection to a scrotal gangrene, identification of multiple underlying pathogenic organisms and toxaemia. In the 2 female patients, a similar infection developed in the labia majora and perineum and extended to the buttocks and the anterior abdominal wall. PMID- 7791485 TI - [Primary seminoma. A rare mediastinal tumor]. AB - This is a report on three patients with primary mediastinal seminoma. Two patients had no symptoms, and one had had thoracic pain for the last few years. The preoperative diagnosis was thymoma in all cases, and in one patient the radiologist had suspected a seminoma. We removed the tumor after performing median sternotomy (n = 2) and anterolateral left thoracotomy (n = 1). The presence of a primary gonadal seminoma was excluded with a urological and ultrasound examination. All patients are still alive following adjuvant chemotherapy (n = 2; 120 and 8 months) and radiotherapy (n = 1; 84 months). Chemotherapy consisted of four cycles of cisplatin, etoposide and ifosfamide or combination therapy with cisplatin, bleomycin and velbe. PMID- 7791486 TI - [Reconstruction of the diaphragm with various materials. An animal experiment study]. AB - The relative merits of three methods of diaphragmatic hernia repair were evaluated in animals. Eighty Sprague-Dawley rats underwent laparotomy. The control group had an incision in the diaphragm with primary repair. The other three groups underwent partial resection of the left hemidiaphragm. The defects were repaired in 20 rats with lyophilized Dura, in 20 with polytetrafluoroethylene (PTFE) and in another 20 with absorbable serosa from a cow. Seventy-two animals survived the operation; they were followed up by electromyography (EMG) and post-mortem physical and histological examinations after 3 and 6 months. The EMG showed normal function for the absorbable material. Only scanty physiological waves were registered in the PTFE group. The examination for stretching and stress showed good results for all materials tested. The histological examinations amount to strong foreign body reactions with Dura and PTFE groups. The absorbable bovine serosa had vanished after 3 months postoperatively. It is concluded that bovine serosa can be recommended for diaphragmatic hernia. PMID- 7791487 TI - [Scar carcinoma as a late complication after burns]. AB - Carcinomas, mainly of the squamous cell type, may occur in burn scars from 3 months to 75 years after the burn injury, and they have a poor prognosis. Therefore, unstable scars, chronic ulcers and tumors must be subjected to histological examination as soon as possible. If a malignant tumor is present, the therapy of choice is wide local excision, though in the event of progressive tumor development an ablative procedure may be necessary. Early radical surgery is important. Unstable scars should be investigated to allow prophylactic surgery to be performed if appropriate [4]. Early mobilization of the (mostly elderly) patients is important. Three case reports of patients with burn scar carcinoma are presented. PMID- 7791488 TI - [Hyperextension injury of the lower cervical spine and diagnosis of dorsal unstable motion segments]. AB - Five patients with hyperextension injuries and dorsally instable motion segments are presented. In the diagnosis of posterior instabilities plain roentgenograms demonstrated no characteristic signs of an injured cervical spine. Flexion and extension views detected a mild degree (2 mm) of retrospondylolisthesis in four cases and a widened disc space in one case. In all five patients the MR findings that made use suspect a posterior unstable motion segment were disc protrusions; in addition, in two patients these was hemorrhage in the spinal cord and in one patient cord edema. PMID- 7791489 TI - [Resection and reconstruction of the carina in children and adolescents]. AB - While resection of tracheobronchial segments has become a standard operation in adults, lesions of the carina in children are rare and their treatment is technically more demanding. Since 1980, 8 patients aged 8 to 19 years underwent surgical reconstruction of the carina. The indications were tumors in 5 and non neoplastic lesions in 3. In 3 patients with tumor (2) and advanced histoplasmosis (1), resection of the carina was combined with parenchymal resection. The principles of operative repair include complete resection, with frozen section confirmation in tumors, particular emphasis on adequate mobilization of the airway in children to reduce anastomotic tension, and use of anesthetic techniques that facilitate early extubation. One patient (12.5%) died after complex airway reconstruction for extensive mediastinal fibrosis. Residual malacia in a patient with postpneumonectomy syndrome required successful re resection. Seven patients remain free of anastomotic stricture and tumor recurrence during a mean follow-up of 62 months (range 5 to 132 months), with expected preservation of lung function. Late bronchoscopy in 5 patients 6 months to 11 years after operation demonstrated growth of the luminal diameter and patent anastomoses. Carinal reconstruction in children is occasionally required, succeeds in general, and does not result in late problems at the anastomosis. PMID- 7791490 TI - Mycobacterial infection after liver transplantation. AB - Tuberculosis occurred in 5 (1.2%) of 462 liver transplant recipients. De novo infection was assumed in 4 patients and a recurrent infection in 1. The clinical courses varied, from asymptomatic open lung tuberculosis to disseminated disease with cerebral tuberculoma and convulsions. Four patients survived with anti tuberculous triple-drug therapy. Very few cases of tuberculosis after liver transplantation have been reported (4 patients in the medical literature and 5 patients in this paper). However, the incidence, course of infection, and outcome seem to be similar to those of tuberculosis in renal transplant recipients, approximately 150 cases of which are known. PMID- 7791492 TI - [Direct electrostimulation of sacral spinal nerves within the scope of the diagnosis of anorectal function]. AB - A technique is demonstrated to evaluate the functional relevance of the sacral spinal nerves regarding anal sphincter function. Sacral spinal nerves S2, S3, S4 can be reached selectively for electrical stimulation by a dorsal approach through the sacral foramina. Electrical stimulation of S3 and S4 results in visible contraction of the different striated muscular anal sphincter components and in an increase of anal canal closure pressure. These effects differ among individuals. Thus, the functional relevance of each single sacral spinal nerve on the striated muscular anal sphincter can be tested specifically. PMID- 7791491 TI - [Reactivity of cortical bone capillaries. Functional TEM analysis with adrenaline, ATP and insulin]. AB - In order to study any morphological effects that vasoactive drugs might exert on cortical bone capillaries, Swiss mice received one intravenous bolus injection each of epinephrine, ATP and insulin. In one control group saline solution was injected and another was not treated. All animals were handled in the same way. A piece of the tibia diaphysis was resected and prepared for transmission electron microscopy (TEM). The lumina and the endothelia of capillaries were submitted to computerized morphometry. Some significant changes were noted: epinephrine increases both the width of the lumen and the endothelium. ATP decreases the endothelium. Insulin (hypoglycaemia?) thickens the endothelium. These finding suggest some physiological hypotheses: the epinephrine-induced widening of the lumen and the thickening of the endothelium might reflect a decreased extravasal space and oedema of cortical bone that might cause the diffusion of minerals to take longer. Intracortical perfusion pressure would then decrease and the bone perfusion rate increase. ATP might reduce the transcapillary diffusion time and increase the extravasal space in cortical bone. Apparently there are specific insulin receptors in cortical bone capillaries. PMID- 7791494 TI - Applications of lasers in gastroenterology. AB - In this article the clinical uses of lasers in gastroenterology are reviewed. The endoscopic delivery of light for therapeutic as well as diagnostic purposes is discussed. Current research directions in the field are also indicated where appropriate. PMID- 7791493 TI - [Follow-up of plasma endothelin and serum interleukin 2 receptor level after liver transplantation]. AB - In a prospective study levels of interleukin-2 receptors (Il-2-R) in serum and of endothelin (ET) in plasma were sequentially determined in 97 patients (39 women, 58 men) before and after liver transplantation (Ltx). The aim of the study was no evaluate the correlation and the time course of these two parameters after Ltx. The postoperative levels of Il-2-R and ET were higher in transplant recipients with no postoperative complications than in patients who had undergone operations to the liver. Patients suffering from acute rejection episodes after transplantation had more markedly increased Il-2-R and ET levels than those with an uneventful course, and this persisted for 3 months. A significant rise of Il-2 R concentrations 3-6 days before a biopsy confirmed rejection proved to have a sensitivity of 68% and a specificity of 68% respectively. A corresponding ET increase preceded rejection episodes confirmed by biopsy with a sensitivity of 62% and a specificity of 67%, respectively. These laboratory data can be obtained daily: they cannot undermine the "gold standard" of liver biopsy, but they are extremely beneficial in determining the timing and indication for the liver biopsy. PMID- 7791495 TI - Laser safety. AB - Safety has always been an important aspect of any laser application in surgery and medicine. In any review of the laser surgery literature, several issues continue to dominate. These issues include: wearing eye protectors, dealing with the plume of vaporized tissue, and controlling potential fire hazards. No one denies that lasers can pose a serious hazard to the eye, but the decision to wear eye protectors in all procedures has been frequently questioned. The degree of effort needed to minimize the very serious risk from chronic breathing of vaporized tissue also requires judgment. Aside from a few eye injuries from a laser beam exposure, most serious accidental injuries (and even deaths) reported to date from the laser beam itself can be traced to the ignition of surgical drapes and airway tubes. PMID- 7791496 TI - Evaluation of a fluorescence feedback system for guidance of laser angioplasty. AB - BACKGROUND AND OBJECTIVE: Laser-induced fluorescence spectroscopy (LIFS) may be capable of guiding laser angioplasty by discriminating normal and atherosclerotic artery and by determining catheter-tissue environment. Previous optical multichannel analyzer based LIFS systems have been expensive and cumbersome. To simplify LIFS, a system based on photomultiplier tubes was developed and evaluated. STUDY DESIGN/MATERIALS AND METHODS: Tissue fluorescence was induced by a helium cadmium laser (wavelength = 325 nm, power = 0.2-0.5 mW), collected by clinical multifiber laser angioplasty catheters and directed through one of two filters (10 nm bandpass, 380 nm or 440 nm peak transmission) to a photomultiplier tube. An LIFS ratio was defined as the relative intensity at 380:440 nm after calibration with an elastin fluorescence spectrum; 157 coronary artery cadaveric specimens were evaluated spectroscopically and histologically. To evaluate the utility of LIFS to optimize catheter position by determining catheter-tissue contact, by determining saline dilution of blood, and by orienting eccentric multifiber catheters a new variable, the total fluorescence intensity (TFI) was defined as the sum of arterial fluorescence intensities at 380 nm and 440 nm. TFI was recorded in vitro through multifiber catheters from 20 arterial specimens in vitro in blood and evaluated as a function of the catheter-to-tissue distance (d) over a range from 0 to 400 mu. RESULTS: Defining normal specimens as those with an intimal thickness < or = 200 mu, and atherosclerotic as those with an intimal thickness > 200 mu, 47/50 (94%) normal and 85/107 (79%) atherosclerotic specimens were correctly classified using a threshold LIFS ratio of 2.0. Mean (+/- SE) normal ratio was 1.76 +/- 0.02 and mean atherosclerotic ratio was 2.78 +/- 0.08 (P < or = 0.01). The classification accuracy of atherosclerotic specimens increased with intimal thickness so that 95% of atherosclerotic specimens (69/73) with intimal thickness > or = 400 mu were correctly classified. TFI was capable of determining catheter-tissue contact as maximal TFI was recorded with the catheter in contact with the tissue (d = 0 mu) and decreased markedly with distance (to 52 +/- 6% at d = 100 mu, 19 +/- 4% at d = 200 mu, and 3 +/- 1% at d = 300 mu). TFI was recorded from ten arterial specimens in blood/saline mixtures ranging in hematocrit from 0% (saline) to 50% (whole blood). TFI was capable of detecting saline hemodilution of blood as TFI decreased markedly at higher hematocrits such that TFI could only by recorded at hematocrits < 10% for catheter-to-tissue distances > or = 300 mu. TFI was recorded through ecentric multifiber catheters from 25 arterial specimens and eval-uated as a function of the degree of catheter-tissue overlap. TFI was capable of detecting maximal catheter-tissue overlap as TFI correlated linearly with the area (A) of overlap (TFI = 1.12 A + .07, r = 0.92). CONCLUSIONS: By discriminating atherosclerotic from normal tissue and by confirming catheter-tissue contact and saline hemodilution, fluorescence feedback should minimize irradiation of normal tissue and/or blood and enhance the safety and efficacy of laser angioplasty. PMID- 7791497 TI - Effect of midinfrared holmium: YAG laser angioplasty with and without balloon angioplasty on acute outcome and restenosis in atherosclerotic femoral arteries in rabbits. AB - BACKGROUND AND OBJECTIVE: Pulsed laser may lessen vascular damage and reduce restenosis. This study examined the acute and chronic effects of midinfrared laser angioplasty with and without balloon angioplasty in atherosclerotic femoral arteries in rabbits. STUDY DESIGN/MATERIALS AND METHODS: Atherosclerosis was induced in arteries by air desiccation and cholesterol feeding. Arteries were assigned to one of four groups: (1) laser angioplasty with a Thullium/Holmium/Chromium:YAG infrared laser (Eclipse), (2) balloon angioplasty, (3) laser followed by balloon angioplasty, and (4) no intervention. Arteries were examined angiographically and histologically at 2 hours and 28 days. RESULTS: Intervention groups had significant initial gain, but this gain was less with laser alone than after balloon or after laser plus balloon. At 2 hours, laser alone caused greater arterial damage and thrombosis compared to controls. At 28 days, arteries treated with laser plus balloon had greater narrowing compared with arteries treated with balloon angioplasty. By multivariate regression analysis, the severity of the pre-intervention stenosis (P = 0.001) and intervention with laser plus balloon (P = 0.01) correlated independently with the severity of luminal narrowing at 28 days. CONCLUSION: Midinfrared Ho:YAG laser angioplasty resulted in substantial acute damage with increased frequency of thrombus formation in this rabbit model. arteries treated with laser alone had suboptimal initial gain and more obstruction by plaque at 28 days compared to nonintervened arteries. The adjunctive use of balloon angioplasty improved initial gain, but correlated with smaller luminal diameters and more severe narrowing by plaque at 28 days. PMID- 7791498 TI - Laser-induced release of liposome-encapsulated dye to monitor tissue temperature: a preliminary in vivo study. AB - BACKGROUND AND OBJECTIVE: The objective of this in vivo study was to assess the possible use of temperature-sensitive liposomes as a new approach to monitor the temperature induced by a laser. STUDY DESIGN: An in vivo/ex vivo study was performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye. MATERIALS AND METHODS: Temperature-sensitive liposomes (DSPC: Di Stearoyl-Phosphatidyl-Choline) were loaded with carboxyfluorescein. These liposomes (1 ml solution) were injected into adult male Wistar rats. Two hours later, the liver was exposed and irradiated with a 100 W Nd:YAG laser using pulses lasting from 100 to 260 ms. Simultaneously, the surface temperature was recorded with a thermographic camera. The fluorescence emission was measured with a fluorescent imaging system. RESULTS: The results showed that the dye was released in response to laser energy. The amount of the drug release increased linearly with increasing temperature in the range 42-60 degrees C. Moreover, the release occurred in a short period of time upon brief exposure to its phase transition temperature. CONCLUSION: The feasibility of temperature monitoring by using laser-induced release of liposome-encapsulated dye was demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues such as blood vessels. PMID- 7791500 TI - Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy. AB - BACKGROUND AND OBJECTIVE: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. STUDY DESIGN/MATERIALS AND METHODS: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. RESULTS: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. CONCLUSION: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH. PMID- 7791499 TI - Optical properties of human articular tissue as implication for a selective laser application in arthroscopic surgery. AB - BACKGROUND AND OBJECTIVE: Optical density of normal and pathological hyaline cartilage, meniscus, and synovium is determined using native and laser-irradiated tissue samples in order to examine potentials for a selective laser ablation. STUDY DESIGN/MATERIALS AND METHODS: One hundred forty-four autopsy specimens were irradiated in a direct contact mode using a XeCl excimer laser (lambda = 308 nm; 20 ns; 40 Hz; 40 +/- 2.1 J/mm2; 800 microns fused silica fiber) and a continuous wave Nd:YAG laser (lambda = 1,064 nm; 1 s; 124 +/- 5.4 W/mm2; 600 microns fused silica fiber). Transmission spectra were obtained by microspectrophotometry in a spectral range from 250 to 770 nm. RESULTS: In the ultraviolet spectrum analyzed, optical density (OD) is calculated to 0.81 +/- 0.05 for native hyaline cartilage, to 1.0 +/- 0.07 for meniscal tissue, and to 0.68 +/- 0.04 for synovium. With increasing wavelength the OD steadily decreases reaching mean values of 0.06 +/- 0.01, 0.13 +/- 0.03, and 0.15 +/- 0.04 at 750 nm. Compared to normal tissue degeneration of cartilage and meniscus lead to a significant increase in OD with a maximum relative OD of 4.39 and 1.26, respectively (P < .001 and P < .01). In synovitis the OD increases with a maximum ratio of 1.45:1 (P < .01). Following Nd:YAG laser exposition the OD of the coagulated zone exceeded the value of native tissue by a factor of 9.71 for cartilage, 4.71 for meniscus, and 3.04 for synovium (P < .001). Excimer irradiation leads to a 3.38-fold increase in OD for cartilage, 2.23-fold for meniscal tissue, and 1.6-fold for synovium (P < .01). CONCLUSION: The results presented indicate that a preferential ablation of pathological tissue structures in articular surgery is possible by selecting laser systems with an appropriate spectral emission range. However, thermal laser tissue interaction may lead to severe alterations in optical properties reducing potentials of a preferential or selective laser application. PMID- 7791501 TI - Lethal photosensitisation of Staphylococcus aureus in vitro: effect of growth phase, serum, and pre-irradiation time. AB - BACKGROUND AND OBJECTIVES: Staphylococcus aureus can be killed by low-power laser light in the presence of aluminium disulphonated phthalocyanine (AlPcS2). The purpose of this study was to determine the effect of pre-irradiation time (PIT), the presence of serum, and the physiological state of the organism on the kills achieved. STUDY DESIGN/MATERIALS AND METHODS: To determine the effect of PIT on killing, suspension of methicillin-resistant S. aureus (MRSA) were incubated in the dark with 12.5 micrograms/ml of AlPcS2 for 60 s or 300 s, and survivors were enumerated after exposure to 1.2 J of light from an 11-mW gallium aluminium arsenide laser. The susceptibility of MRSA in its various growth phases was determined in a similar manner using a PIT of 300 s. The effect of serum on killing was determined using stationary phase cells resuspended in horse serum. RESULTS: Using a PIT of either 60 s or 300 s, 10(6) cfu (99.9%) of MRSA were killed. There was little difference in the susceptibility of lag-, logarithmic-, or stationary-phase cells, the kills being 99.9%, 99.8%, and 99.9%, respectively. Although kills were reduced in the presence of serum, 99.6% of MRSA were killed using a light dose of 1.2 J. CONCLUSION: These results demonstrate that MRSA can be rapidly sensitised by AlPcS2 to killing by low-power laser light, that killing is not dependent on the organism's growth phase, and that substantial kills can be achieved in the presence of serum. PMID- 7791503 TI - Carbon dioxide laser therapy of a widespread epidermal nevus. AB - BACKGROUND AND OBJECTIVE: The treatment of epidermal nevi is difficult and often unsatisfactory. Many therapeutic approaches have been tried, of which the surgical methods including lasers aim to avoid recurrences and hypertrophic scarring. Here we report the case of a widespread, life-impairing epidermal nevus, summarize the available treatment modalities, and discuss CO2 laser therapy with respect to the clinically soft variants of these developmental defects. STUDY DESIGN/PATIENTS AND METHODS: A patient with a widespread, recurrent, biopsy-proven epidermal nevus was treated with a 10,600-nm CO2 laser. After test treatments in local anaesthesia, four sessions were performed under general anaesthesia each with a follow-up time of 4 years to date. RESULTS: CO2 laser vaporization resulted in complete removal of the treated nevus without any obvious scarring. The patient is free of recurrence 4 years postoperatively. CONCLUSION: CO2 laser treatment of epidermal nevi is a useful modality in selected variants. PMID- 7791502 TI - Model study to investigate the contribution of spallation to pulsed laser ablation of tissue. AB - BACKGROUND AND OBJECTIVE: Absorption of a short laser pulse produces high thermoelastic stress in the irradiated volume. The relaxation of this stress at a free (tissue-air) surface leads to tensile loading, resulting in mechanical spallation. Using model substances, we investigated the role of this effect in tissue ablation. STUDY DESIGN/MATERIALS AND METHODS: Stained water and gelatine were irradiated with short pulses (8 ns duration) from a Nd:YAG laser at 1,064 nm wavelength. The dynamics of the induced effects were observed with laser-flash photography and stress wave detection. RESULTS: Spallation is indicated by the formation of cavitation bubbles below the irradiated surface and is strongly influenced by impurities serving as nucleation sites. Material ejection due to spallation was observed in the liquid sample at a fluence leading to a temperature below the boiling point but needed a temperature in excess of 100 degrees C in gelatine, owing to the small mechanical energy available for this process, estimated to be < 1%. CONCLUSION: The mechanical action of thermoelastic stress waves is characterized by high stress amplitudes but low energetic efficiency. A model combining spallation and vaporization is therefore proposed for efficient tissue ablation. PMID- 7791504 TI - Laparoscopic surgery of chronic hyperandrogenic anovulation. AB - The review describes briefly the clinical and endocrinological characteristics of chronic hyperandrogenic anovulation (CHA), as well as ovulation induction by hormone therapy (therapy of first choice) and by classical wedge resection. The main purpose of this study, however, is to compare different laparoscopic treatments of CHA, with emphasis on laser treatments by argon, CO2, Nd:YAG, and frequency-doubled Nd:YAG laser. The overall results of laparoscopic treatments in hormone-therapy-resistant patients with CHA are encouraging and the results are comparable. In the studies considered in this review, ovulation was induced for longer or shorter periods in 21 out of 31 patients (68%) after ovarian biopsy, in 57 out of 73 patients (78%) after electrosurgery, and in 82 out of 118 patients (70%) after laser treatment. Subsequent conception occurred in 44%, 40%, and in 41% of the patients, respectively. Of interest is the fact that some hormone therapy-resistant patients become sensitive to Clomiphene after laparoscopic treatment, giving an overall percentage of ovulation and an overall pregnancy rate of 89% and 54%, respectively, for electrosurgery, and of 88% and 50%, respectively, for laser treatment. Unfortunately, adhesion formation, a serious complication of surgical treatment of the ovaries, is still a drawback using laparoscopic surgical techniques. PMID- 7791506 TI - Nonselective ETA/ETB receptor antagonist blocks proliferation of rat vascular smooth muscle cells after balloon angioplasty. AB - To elucidate the role of endothelin receptor subtypes in the abnormal proliferation of vascular smooth muscle cells (VSMC) associated with vascular injury, we have investigated the effects of a novel and potent nonselective ETA/ETB receptor antagonist (TAK-044) on the proliferation of rat VSMC in vitro and in vivo. TAK-044 dose-dependently inhibited DNA synthesis stimulated by 10( 7) M ET-1 in cultured rat VSMC from the late passage with the approximate IC50 of 6 x 10(-8) M. After balloon angioplasty, the neointimal lesion in the injured carotid arteries in the TAK-044-treated group (0.052 +/- 0.014 mm2) was significantly (p < 0.05) decreased compared to that in control group (0.26 +/- 0.045 mm2), while the medial surface area was not affected. The intima/media ratio in the TAK-044 group (31 +/- 6%) also significantly (p < 0.05) decreased from that of the control group (148 +/- 25%). Our data suggest that nonselective ETA/ETB receptor antagonists may be therapeutic potential for prevention against the intimal thickening associated with vascular injury. PMID- 7791505 TI - Rolipram, a selective c-AMP phosphodiesterase inhibitor suppresses oro-facial dyskinetic movements in rats. AB - Since striatal dopamine D2 receptor supersensitivity in the etiology of tardive dyskinesia has been suggested and dopamine D2 receptors are known to inhibit adenylate cyclase activity resulting in a decrease of cyclic adenosine 3',5' monophosphate (cAMP) levels, we hypothesized that an increase in cAMP levels ameliorates the condition. In the present study, 21-day haloperidol treatment (1.5 mg/kg I.P.) in rats resulted in an increase in striatal [3H]-spiperone (D2) binding whereas [3H] SCH23390 (D1) binding was unaltered. This haloperidol treatment also induced a significantly increase in the frequency of involuntary chewing movements and tongue protrusions, which are considered as a model of tardive dyskinesia. These dyskinetic movements were suppressed by administration of rolipram (0.5 and 1.0 mg/kg I.P.), an inhibitor of the cAMP phosphodiesterase type IV. The present results suggest that selective cAMP phosphodiesterase type IV inhibitors could be putative therapeutic drugs for tardive dyskinesia. PMID- 7791508 TI - Effects of 2 alpha-DHET and its optical isomers on muscarinic and nicotinic receptors. AB - The agent 2 alpha-(2', 2'-disubstituted-2'-hydroxy-ethoxy) tropane (2 alpha DHET), its optical isomers and atropine were compared in their ability to inhibit specific [3H]QNB binding to muscarinic receptors of guinea pig ileum and to antagonize oxotremorine- and nicotine-induced contractions of isolated guinea pig ileum. A good correlation was observed between the affinities to muscarinic receptors and the antimuscarinic potencies in isolated guinea pig ileum. The binding data for 2 alpha-DHET and its isomers were also consistent with their central and peripheral pharmacological activity in vivo. Compounds with 2'R configuration are more suitable to the stereostructure of the binding sites of muscarinic receptors than that of 2'S configuration. PMID- 7791507 TI - Nitrous oxide and xenon enhance phospholipid-N-methylation in rat brain synaptic plasma membranes. AB - Halothane and isoflurane increase the rate of phospholipid methylation (PLM) in rat brain synaptosomal membranes, a process linked to the coupling of neuronal excitation to neurotransmitter release. In contrast, synaptic plasma membrane (SPM) Ca2+ ATPase (PMCA) pumping is reduced by exposure to halothane, isoflurane, xenon and nitrous oxide (N2O). To examine further the relationship between PLM, PMCA and anesthetic action, we investigated the effect of clinically relevant concentrations of two less potent anesthetic gases, N2O and xenon, on PLM in SPM. Biochemical assays were performed on SPM exposed to 1.3 MAC of N2O (2 atm), 1.3 MAC of xenon (1.23 atm) or an equivalent pressure of helium for control. N2O or xenon exposure increased PLM to 115% or 113%, respectively, of helium control (p < 0.02). Similar exposures to N2O or xenon depressed PMCA activity to 78% and 85% of control (p < 0.05). Observations that PLM and PMCA are both altered by a wide variety of inhalation anesthetic agents at clinically relevant partial pressures lend support to a possible involvement and interaction of these processes in anesthetic action. PMID- 7791509 TI - The role of 5-HT2A receptors in antipsychotic activity. AB - The correlation between the clinical activity of antipsychotic agents and their affinity for the D2 dopamine receptor has been the mainstay of the hypothesis that schizophrenia is due to excessive dopaminergic function. More recently, the unique clinical profile of the atypical antipsychotic clozapine has been proposed to involve actions on additional receptor systems. In particular, the high affinity of clozapine for the 5HT2A receptor subtype has been suggested to contribute to its reduced side-effect liability, greater efficacy and its activity in therapy-resistant schizophrenia. We have used the highly selective 5 HT2A antagonist MDL 100,907 to explore the contribution of 5-HT2A receptor blockade to antipsychotic activity. Biochemical, electrophysiological and behavioral studies reveal that selective 5HT2A receptor antagonists have the preclinical profile of an atypical antipsychotic. The limited clinical evidence available also suggests that compounds producing 5-HT2A receptor blockade are effective, in particular, against the negative symptoms of schizophrenia. PMID- 7791510 TI - Superoxide dismutase in the nonobese diabetic (NOD) mouse: a dynamic time-course study. AB - Superoxide dismutase (SOD) levels, thought to be the first cellular defence against free radicals, were studied in the nonobese diabetesprone (NOD-p) mouse, an animal model of type 1 diabetes in which about 100% of females and 20% of males become diabetic. Nonobese diabetes nonprone (NON-p) mice were used as controls. Animals were followed from 5th to 22nd week of life. Results show that SOD levels in female NOD-p mice are extremely low. In males, values are considerably higher than in females but still lower than values found in control mice. Moreover, SOD levels did not significantly change with age, degree of insulitis or level of diabetes. Islet beta cells in this strain, therefore, seem to be poorly protected against the negative effects of free radicals and this may predispose to diabetes. Furthermore, alterations of SOD may not be directly related to the development of the disease as the enzyme's activity is not further modified with age or the progression of diabetes. PMID- 7791512 TI - Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system. AB - Estrogen exhibits a variety of actions, including immuno-modulatory effects, in vivo and in vitro. The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood. We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes (PMNs), which are important in the immune response. The agent, 17 beta-estradiol, but not 17 alpha-estradiol, significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner (control vs estrogen 10(-10)-(-6) M, P < 0.05). Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs (10(-10) mol). Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists, eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of PMNs, restoring it to the control level. These observations suggest that 17 beta-estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism. In addition, the level of estradiol in human plasma, which PMNs were drawn, showed a close, inverse correlation with the PMNs chemotaxis to FMLP (r = -0.821 p < 0.001). Estrogen may modify the activity of neutrophils during the normal menstrual cycle, not only during pregnancy, and influence inflammation. PMID- 7791511 TI - Neuroleptic effects on acquisition and performance of learned behaviors: a reinterpretation. AB - It is well-established that dopamine facilitates motor responsiveness. However, neuroleptics--drugs that block dopaminergic transmission--do not affect equally motor responses to environmental stimuli: responses to some stimuli seem completely preserved while responses to other stimuli are greatly disturbed. For example, escape responses to a noxious stimulus are typically preserved, even when avoidance to a cue predicting the noxious stimulus is absent. In this paper, we propose a connectionist account of this differential effect. We assume that dopamine determines the "gain" of the function relating the activation of a neural ensemble to its excitatory or inhibitory input. Because such a function is necessarily non-linear, we show that the influence of gain on whether a neural ensemble reaches a "threshold" of activation is critically different for low and high excitatory drives. This analysis makes specific predictions about the effect of neuroleptics on motor responses at different stages of training. PMID- 7791513 TI - Prejunctional muscarinic autoreceptors on horse airway cholinergic nerves. AB - Muscarinic autoreceptors on horse airway cholinergic nerves were studied by examining the effects of muscarinic receptor antagonists on electrical field stimulation (EFS)-induced acetylcholine (ACh) release in trachealis preparations. All the antagonists including atropine (non-selective), pirenzepine (M1 selective), AF-DX 116 (M2-selective), and hexahydrosiladifenidol (M3-selective) augmented ACh release concentration-dependently. The augmentation was not due to displacement of ACh molecules from tissue receptors into the bath liquid because incubation with atropine after EFS had no influence on the measured amount of ACh. Hexahydrosiladifenidol was more potent in inhibiting ACh-induced muscle contraction, which is known to be mediated by M3 receptors, than in augmenting ACh release. The maximal ACh release rate in response to the selective antagonists was much less than that following atropine. Furthermore, the concentrations of the selective antagonists required to augment ACh release far exceeded their KdS for M1, M2, or M3 receptors. These observations suggest that the muscarinic autoreceptors on horse airway cholinergic nerves may belong to a novel subtype. PMID- 7791514 TI - A seric low molecular weight factor modulates IGFs effects on chick cartilage metabolism. AB - The effects of recombinant human insulin-like growth factors (rhIGF-I and rhIGF II) alone and in combination with a partially purified serum low molecular weight growth factor (LMW-GF) were studied by measuring proteoglycan (PG) and total protein synthesis by chick embryo cartilage. rhIGF-I alone did not increase the incorporation of L[3H]serine or [35S]Na2SO4 into whole cartilages. LMW-GF + rhIGF I markedly increased the incorporation of these precursors. rhIGF-I alone stimulated D[3H]glucosamine uptake, and LMW-GF increased the effect of rhIGF-I. These results for whole cartilage were reproduced with glycosaminoglycans (GAG) extracted from cartilage. LMW-GF acted in synergy with rhIGF-I to stimulate PG core protein synthesis, xylosyl transferase activity and sulfation. Total protein synthesis, as measured by [35S]methionine uptake, was not altered by rhIGF-I. LMW GF plus rhIGF-I increased the incorporation of this precursor into whole cartilage. The effect of rhIGF-II on PG synthesis was different from that of rhIGF-I. rhIGF-II alone stimulated GAG chain lengthening and sulfation. LMW-GF did not modify the effect of rhIGF-II on these steps. In contrast, rhIGF-II did not stimulate the synthesis of core protein. LMW-GF plus rhIGF-II increased the [3H]serine incorporation into the whole cartilage, but this combination did not stimulate the uptake of [3H]serine into extracted GAG. rhIGF-II plus LMW-GF were also without effect on xylosyl transferase activity. The combination of these factors increased the [35S]methionine incorporation into cartilage total proteins. These results suggest that rhIGF-II does not regulate the PG core protein synthesis, but in combination with LMW-GF, stimulates the synthesis of proteins other than proteoglycan core protein. PMID- 7791515 TI - A new extrapolation method from animals to man: application to a metabolized compound, mofarotene. AB - Allometric scaling (a technique which uses data obtained in laboratory animals to predict human pharmacokinetics) works well for drugs that are cleared intact, but is less successful with extensively metabolised compounds. This paper describes a new method to improve the accuracy of such projections, by integrating metabolic data obtained in vitro (e.g. with liver microsomes or hepatocytes) into these calculations. The approach was used prospectively, to predict the clearance of mofarotene (Ro 40-8757) in humans from in vivo kinetic data obtained in mouse, rat and dog. This compound was selected to illustrate this approach because it is exclusively eliminated through metabolism. Without the metabolic correction or using empirical correcting factors, the values predicted for man were 2.7 and 0.6 ml/min/kg. This fell outside the range subsequently obtained in healthy volunteers dosed orally with 300 mg of mofarotene (7.5 +/- 4.0 ml/min/kg, n = 12). However, inclusion of the microsomal or hepatocyte data gave values of 5.1 and 4.2 ml/min/kg, respectively, illustrating that the integration of in vitro metabolic data improves the accuracy of kinetic extrapolations. In contrast to the existing empirical techniques, this approach offers a rational basis to predict clearance of metabolized compounds in human. PMID- 7791516 TI - "It's the genes, stupid". Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. AB - In this review we highlight the information available on the genetic polymorphism of cytochrome P4502D6 expression in man. An absent function of this enzyme is observed in 7-10 percent of the Caucasian population which are referred to as Poor metabolizers as opposed to the remainder of the population (Extensive Metabolizers). More than 30 widely used drugs have been identified as substrates for CYP2D6. Disposition and action of these compounds depend on the individual phenotype. Both the molecular bases of the variable enzyme activity and the consequences for drug therapy are outlined. While mutations on the DNA level have been investigated in great detail larger scale clinical trials are lacking and information on therapeutic consequences of CYP2D6 mediated polymorphic drug oxidation is restricted to case reports. Besides these implications for drug metabolism several lines of evidence indicate that CYP2D6 could be involved in biotransformation of endogenous compounds. PMID- 7791517 TI - Effects of monosialoganglioside on dopaminergic supersensitivity. AB - The effects of monosialoganglioside (GMl) treatment on dopaminergic supersensitivity induced by long-term haloperidol administration were studied; both general activity of rats observed in an open-field and apomorphine-induced stereotyped behavior were used as experimental parameters. GMl per se (5.0 mg/kg, twice daily, for 30 days) did not modify rat behavior, but when given in combination with haloperidol (1.0 mg/kg, twice daily, for 30 days) it increased neuroleptic withdrawal symptoms as detected in both models. When GMl (5.0 mg/kg, twice daily) was administered after abrupt withdrawal from haloperidol (1.0 mg/kg, twice daily, for 30 days), it attenuated the increases in both general activity of rats observed in the open-field and apomorphine-induced stereotyped behavior. These results suggest that GMl may affect synaptic plasticity, facilitating the induction of the adaptative changes in receptor function (up and down-regulation), following long-term haloperidol treatment and withdrawal. PMID- 7791518 TI - Increased receptor-mediated phospholipase D activation and Ca2+ mobilization in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats. AB - Phospholipase D activation was investigated in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats. Stimulation of the cells with formyl-Met-Leu-Phe resulted in a time- and dose-dependent increase in phosphatidylethanol in the presence of ethanol, and this lipid formation in cells prepared from diabetic rats was enhanced as compared to that in the case of nondiabetic rats. Furthermore, the increase in the intracellular Ca2+ concentration was also enhanced in the stimulated cells from diabetic rats. Under the present conditions, N-acetyl-beta-glucosaminidase release and superoxide generation, which are known to be dependent on phospholipase D activation, were higher in the cells from diabetic rats than those in the cells from control rats. However, there was no difference in the dissociation constant and the number of binding sites for formyl-Met-Leu-Phe between the cells from diabetic and control rats. Phosphatidylethanol formation, N-acetyl-beta-glucosaminidase release and superoxide generation in response to ionomycin or 4 beta-phorbol 12-myristate 13 acetate were not enhanced in diabetic rat cells, as compared with those in control rat cells. These results suggest that receptor-mediated phospholipase D activation and Ca2+ mobilization are enhanced in diabetic rat polymorphonuclear leukocytes, which might be due to acceleration of receptor-mediated signaling. PMID- 7791521 TI - Quantitative distribution of the delta opioid receptor mRNA in the mouse and rat CNS. AB - We have used a sensitive solution hybridization assay that employs a riboprobe obtained from the mouse delta opioid receptor (DOR) coding sequence to quantitate the relative abundance of DOR mRNA in the central nervous system (CNS) of the adult mouse and rat. In brain Poly A+ RNA extracts this riboprobe hybridized to a single 10 kb transcript from mouse and two transcripts, one of 12 and the other of 4.5 kb in size from rat. In mouse CNS the highest levels of DOR mRNA were found in the caudate-putamen at 3.3 +/- 0.1 (SEM) pg/micrograms RNA. DOR mRNA levels in the range from 2.6 to 2.1 pg/micrograms RNA were measured in frontal cortex, nucleus accumbens, whole brain and olfactory tubercle. Spinal cord, periaqueductal gray and hippocampus had DOR mRNA levels in the range from 1.8 to 1.5 pg/micrograms RNA, while medial thalamus and cerebellum had the lowest levels (0.5 pg/micrograms RNA). These results correlate with the reported relative distribution of DOR mRNA in mouse using an in situ hybridization technique. In rat CNS, the highest levels of DOR mRNA were measured in caudate-putamen at 2.3 +/- 0.1 pg equivalents/micrograms RNA. Whole brain, cerebral cortex, olfactory bulb and brain stem had levels in the range from 1.5 to 0.9 pg equivalents/micrograms RNA while the lowest DOR mRNA levels were measured at 0.5 pg equivalents/micrograms RNA or less in thalamus, hippocampus, substantia nigra and cerebellum. This study demonstrates the ability of solution hybridization assays to quantitate homologous (mouse) as well as similar but heterologous (rat) DOR mRNA levels. PMID- 7791519 TI - Agmatine, the bacterial amine, is widely distributed in mammalian tissues. AB - We sought to determine whether agmatine (decarboxylated arginine), a bacterial product recently discovered for the first time in mammalian brain, was contained in other organs. A method was developed for isolation of agmatine from tissue and detection by RP-HPLC following solid-liquid extraction and derivatization with o phthalaldehyde and mercaptoethanol. Recovery was about 80% and the limit of fluorometric detection was about 10 pg on column. In male Sprague-Dawley rats agmatine was unevenly and widely distributed in many tissues confirming its presence in mammals. The highest concentration (approximately 71 ng/mg net weight) was found in stomach, with aorta and small intestine next, followed by smaller levels in spleen, adrenal, aorta, and skeletal muscle and brain. Serum concentrations were high. Agmatine in male Long Evans rats of 3, 12, and 24 months of age demonstrated similar but not identical tissue distribution without any effect of aging. Since agmatine binds to alpha 2-adrenergic and imidazoline receptors, is bioactive in a number of tissues, is contained in neurons and is found in serum and tissues, the findings are consistent with a potential role for agmatine as a neurotransmitter and/or hormone. It also raises the possibility that agmatine may, as in bacteria, serve as a polyamine precursor along metabolic pathways previously not detected in mammals. PMID- 7791520 TI - A permanent human cell line (EA.hy926) preserves the characteristics of endothelin converting enzyme from primary human umbilical vein endothelial cells. AB - Purification of endothelin converting enzyme (ECE) from endothelial cells has been hindered by the difficulty in obtaining primary endothelial cells in large quantity. We therefore tested transformed human umbilical vein endothelial cells (EA.hy926) for ECE activity. Our data clearly demonstrate that this transformed cell line preserves the ECE properties of the primary cell line. These include: (i) one sharp activity optimum at neutral pH; (ii) characteristics typical of a metalloprotease; (iii) IC50 value for phosphoramidon of 1.8 microM (2.7 microM for HUVEC); (iv) no inhibition by captopril and thiorphan, inhibitors of angiotensin converting enzyme and neutral endopeptidase 24.11. The enzyme showed a substrate specificity for big ET-1:big ET-2:big ET-3 in a ratio of 40:2.5:1. This report presents evidence that a permanent human endothelial cell line, EA.hy926, preserves the ECE activity of HUVEC and is useful for the study of ECE and its regulation of ET-1 production. PMID- 7791523 TI - Alterations of serum lipid levels and their biological relevances during and after pregnancy. AB - In normal pregnancy, all women displayed a significant elevation of serum triglyceride (TG), total cholesterol (TC), low density cholesterol (LDL-C) and high density cholesterol (HDL-C) during parturition. To study the quantitative changes in serum levels of lipids and their biological relevances during and after pregnancy, blood samples were collected from 62 normally pregnant women throughout gestation and 6 to 12 weeks postpartum. Compared with 184 nonpregnant control subjects, TG, TC, LDL-C and HDL-C were significantly elevated during the second and third trimesters of pregnancy but dropped sharply after pregnancy. To further understand the effect of pregnancy on other metabolic parameters, we compared the relative levels of apolipoproteins such as apolipoprotein A-I (apoA I) and apolipoprotein B (apoB), lipoprotein (a) (Lp(a)) and blood sugar during and after pregnancy. We found that apoB concentration progressively increased with advancing gestation, while the levels of apoA-I, Lp(a) and blood sugar were independent of gestation process. The physiological significance of hyperlipidemia during pregnancy is also discussed in this study. PMID- 7791522 TI - C-natriuretic peptide but not atrial natriuretic peptide increases cyclic GMP in cerebral arterial smooth muscle cells. AB - A-type natriuretic peptide (ANP) is found primarily in the heart and is released into the circulation. C-type (CNP) is found principally in the brain and has also been detected in the systemic circulation. When injected, both peptides produce vasodilatation most likely by elevation of guanosine 3'5'-cyclic monophosphate (cGMP) in smooth muscle cells via two distinct receptors, NPR-A and NPR-B. In this present study, we determined the effects of these two peptides on intracellular cGMP in smooth muscle cells cultured from pig cerebral and peripheral arteries. In smooth muscle cells cultured from the left anterior descending coronary artery, ANP and CNP increased cGMP with equal potency and efficacy (EC50 for ANP and CNP, 3.6 +/- 0.2 x 10(-8) M and 6.7 +/- 0.8 x 10(-8) M, respectively). In contrast, in smooth muscle cells from cerebral arteries, ANP was without effect while CNP increased cGMP in a concentration dependent manner (EC50: 9.6 +/- 1.7 x 10(-8) M). Stimulation of the soluble guanylyl cyclase with either nitroglycerin or nitroprusside was equivalent in the two cell types. The pattern of response of intracellular cGMP to CNP and ANP in isolated intact arteries from brain and heart was similar to that found in the cultured cells. These results suggest that smooth muscle cells in cerebral arteries express only NPR-B while cells from peripheral arteries can express both NPR-A and NPR-B. PMID- 7791525 TI - Sigma receptors are expressed in human non-small cell lung carcinoma. AB - N-(2-piperidinoethyl)4-iodobenzamide), IPAB, was used to characterize sigma receptors in non-small cell lung cancer (NSCLC) cell lines. 125IPAB bound with high affinity to large cell carcinoma (NCI-H1299), adenocarcinoma (NCI-H838), and lung carcinoid (NCI-H727) cell lines. Specific IPAB binding was inhibited with high affinity by haloperidol (Ki = 0.6 nM), IPAB (Ki = 14 nM) and 1,3-ditolyl guanidine (DTG) (Ki = 40 nM). Relative to other receptor ligands, IPAB was not readily internalized at 37 degrees C. IPAB had little effect on the growth of NSCLC cells. Scintigraphic imaging studies using 131IPAB in nude mice bearing NCI H838 xenografts visualized the tumor at 24 or 30 hours after injection. These results suggest that sigma receptors which are present on NSCLC cells may be used as external markers for imaging tumors in vivo. PMID- 7791526 TI - Regulation of Biosynthesis and Function of Isopentenoids. Symposium proceedings. Atlanta, Georgia, May 8-12, 1994. PMID- 7791524 TI - Inactivity of phosphoethanolamine, an endogenous GABA analog decreased in Alzheimer's disease, at GABA binding sites. AB - Phosphoethanolamine (PE) is a metabolite of the phospholipid metabolism which is decreased in Alzheimer's disease brain. PE shows a strong structural similarity to the inhibitory neurotransmitter, GABA, and the GABAB receptor partial agonist, 3-amino-propylphosphonic acid. The ability of PE to compete for binding to GABAA and GABAB binding sites was investigated. GABAA sites were studied using [3H]SR 95531 and [3H]muscimol. GABAB sites were studied using [3H]GABA in the presence of isoguvacine to saturate GABAA sites. Total [3H]GABA binding was also examined. PE showed little activity at any of the GABA binding sites investigated. PE was most potent at GABAB sites, but the IC50 of 7.5 +/- 0.75 mM was considerably higher than its maximal physiologic concentration of approximately 1.5 mM. The efficient exclusion of PE from GABA binding sites may be an important physiologic mechanism in the control of inhibitory neurotransmission. The structural basis for this exclusion is discussed in reference to the GABAB partial agonist 3-amino propylphosphonic acid. PMID- 7791527 TI - Some new aspects of isoprenoid biosynthesis in plants--a review. AB - Plants are capable of synthesizing a myriad of isoprenoids and prenyl lipids. Much attention has been focused on 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the enzyme that synthesizes mevalonate and is generally considered responsible for the regulation of substrate flux to isoprenoids. In contrast to vertebrates, where there seems to exist only one HMGR gene, in plants a small family of isogenes appears differentially expressed in regard to location and time. Much less is known in plants about the preceding steps, viz. the conversion of acetyl-CoA to HMG-CoA. An enzyme system has been isolated from radish that can catalyze this transformation, and which shows some unusual properties in vitro. The intracellular localization of the early steps of isoprenoid biosynthesis in plant cells is still a matter of debate. The various observations and hypotheses derived from incorporation and inhibition studies are somewhat contradictory, and an attempt is being made to rationalize various findings that do not at first seem compatible. There are good arguments in favor of an exclusively cytoplasmic formation of isopentenyl pyrophosphate (IPP) via mevalonic acid, but other studies and observations suggest an independent formation in plastids. Other possibilities are being considered, such as the existence of independent (compartmentalized) biosynthetic pathways of IPP formation via the so-called Rohmer pathway. Substrate channeling through the formation of end product specific multienzyme complexes (metabolons) with no release of substrate intermediates will also be discussed. PMID- 7791529 TI - Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review. AB - Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents. Nine of the eleven genes in the portion of the pathway committed exclusively to ergosterol biosynthesis have been cloned, and their essentiality for aerobic growth has been determined. The first three genes, ERG9 (squalene synthase), ERG1 (squalene epoxidase), and ERG7 (lanosterol synthase), have been cloned and found to be essential for aerobic viability since their absence would result in the cell being unable to synthesize a sterol molecule. The remaining eight genes encode enzymes which metabolize the first sterol, lanosterol, to ultimately form ergosterol. The two earliest genes, ERG11 (lanosterol demethylase) and ERG24 (C-14 reductase), have been cloned and found to be essential for aerobic growth but are suppressed by mutations in the C-5 desaturase (ERG3) gene and fen1 and fen2 mutations, respectively. The remaining cloned genes, ERG6 (C-24 methylase), ERG2 (D8AE7 isomerase), ERG3 (C-5 desaturase), and ERG4 (C-24(28) reductase), have been found to be nonessential. The remaining genes not yet cloned are the C-4 demethylase and the C-22 desaturase (ERG5). PMID- 7791528 TI - Developmental regulation of sterol biosynthesis in Zea mays. AB - Sixty-one sterols and pentacyclic triterpenes have been isolated and characterized by chromatographic and spectral methods from Zea mays (corn). Several plant parts were examined; seed, pollen, cultured hypocotyl cells, roots, coleoptiles (sheaths), and blades. By studying reaction pathways and mechanisms on plants fed radiotracers ([2-(14)C]mevalonic acid, [2-(14)C]acetate, and [2 (3)H]acetate), and stable isotopes (D2O), we discovered that hydroxymethylgutaryl CoA reductase is not "the" rate-limiting enzyme of sitosterol production. Additionally, we observed an ontogenetic shift and kinetic isotope effect in sterol biosynthesis that was associated with the C-24 alkylation of the sterol side chain. Blades synthesized mainly 24 alpha-ethyl-sterols, sheaths synthesized mainly 24-methyl-sterols, pollen possessed an interrupted sterol pathway, accumulating 24(28)-methylene-sterols, and germinating seeds were found to lack an active de novo pathway. Shoots, normally synthesizing (Z)-24(28)-ethylidine cholesterol, after incubation with deuterated water, synthesized the rearranged double-bond isomer, stigmasta-5,23-dien-3 beta-ol. Examination of the mass spectrum and 1H nuclear magnetic resonance spectrum of the deuterated 24-ethyl sterol indicated the Bloch-Cornforth route originating with acetyl-CoA and passing through mevalonic acid to sterol was not operative at this stage of development. An alternate pathway giving rise to sterols is proposed. PMID- 7791531 TI - Identification of the active site of vertebrate oxidosqualene cyclase. AB - Active site mapping of rat liver oxidosqualene cyclase (OSC), a 78 kDa membrane bound enzyme, was carried out using the mechanism-based irreversible inhibitor, [3H]29-methylidene-2,3-oxidosqualene. The amino acid sequence of the radiolabeled CNBr peptide fragment showed unexpectedly high similarity to the yeast OSC, plant OSC, and bacterial squalene cyclases. Further, radio analysis established that the two adjacent Asp residues in the highly conserved region (Asp-Asp-Thr-Ala-Glu Ala, or DDTAEA) were equally labeled by the irreversible inhibitor. This result provided the first information on the structural details of the active site of OSC, and showed for the first time the ancient lineage of this vertebrate enzyme to ancestral eukaryotic and prokaryotic cyclases. Interestingly, the covalently modified DDXX(D/E) sequence of rat liver OSC showed surprising similarity to the putative allylic diphosphate binding site sequence of other terpene cyclases and prenyl transferases. The Asp-rich motif may act as a point charge to stabilize incipient cationic charge. PMID- 7791530 TI - Biochemical and physiological effects of sterol alterations in yeast--a review. AB - Considerable progress has been made in the selection and characterization of mutants that are defective in the synthesis of ergosterol in the yeast, Saccharomyces cerevisiae. Mutations in nearly every step of the yeast sterol biosynthetic pathway have been induced and selected. These mutants have been used to elucidate the sequential order of steps in sterol synthesis, to study the mode of action of antifungal agents and to determine the method of resistance of some pathogenic fungi, and to answer questions on the role of sterols in general cell biology. Physiological examination of ergosterol null mutants, lacking all biochemical activity attributed to the particular gene, supports a role for ergosterol in a number of critical functions in the organism. Among the physiological functions attributed to ergosterol are sparking and bulking requirements, involvement in amino acid and pyrimidine transport, resistance to antifungal agents and certain cations, and a requirement for respiratory activity. Those genetic null alleles discussed in this review are erg24, lacking the ability to reduce the delta 14 double bond; erg6, unable to methylate C-24; and erg3, defective in the C-5 desaturase. The different biochemical activities that are disrupted in the ergosterol mutants support a role for ergosterol in a number of critical functions in yeast. PMID- 7791532 TI - 2,3-Oxidosqualene cyclase: from azasqualenes to new site-directed inhibitors. AB - 2,3-Oxidosqualene cyclases (OSC) are enzymes which convert 2,3-oxidosqualene (OS) into polycyclic triterpenoids such as lanosterol, cycloartenol, and alpha- and beta-amyrin. Our interest in the study of OSC is the development of new OSC inhibitors for potential use as hypocholesterolemic, antifungal, or phytotoxic drugs. In particular, we describe the biological activity and the mechanism of a series of acyclic azasqualene derivatives mimicking the C-2, C-8, and C-20 carbonium ions formed during OS cyclization. Some of these carbonium ion analogues are very promising as specific hypocholesterolemic agents. The toxicity, the biodistribution, and the pharmacokinetics of different azasqualene derivatives in mice are also presented. In order to obtain new, site-directed irreversible inhibitors of OSC, a series of squalene derivatives containing functional groups that can link covalently to an active-site thiol group was designed. Among these compounds, squalene maleimide was the most active toward mammalian OSC, whereas squalene Ellman behaved as an irreversible inhibitor of OSC from yeast. PMID- 7791534 TI - Growth of Cucurbita maxima L. plants in the presence of the cycloartenol synthase inhibitor U18666A. AB - Squash, like other Cucurbitaceae, have unique sterol profiles that offer an excellent opportunity to examine the relationship between sterol biosynthesis and plant growth. To determine the effect of sterol biosynthesis inhibition on squash growth, Cucurbita maxima seedlings with and without cotyledons were subjected to increasing concentrations of the cycloarternol synthase (EC 5.4.99.8) inhibitor 3 beta-(2-diethylaminoethoxy)androstenone (U18666A). Inhibition of shoot growth was concentration-dependent (from 0, 2, 5, 10, and 20 microM); plants with intact cotyledons grew to 26.4, 23.7, 21.6, 20.0, and 15.6 cm, respectively, at the above inhibitor concentrations, compared to 25.5, 19.4, 17.0, 12.0, and 11 cm for plants with severed cotyledons. In plants with severed cotyledons, 10 and 20 microM U18666A caused rapid necrosis of the first two, newly emerged, primary leaves, and halted new leaf formation. Secondary root formation was initially affected at all inhibitor concentrations regardless of whether cotyledons were present or not. Vegetative tissue showed a decrease in the accumulation of the major squash sterol, 7,22-stigmastadienol, accompanied by increased accumulation of minor sterol components. Sterol profiles in cotyledons were unaltered. The data show that sterols are crucial for maintaining plant growth and viability, but do not address the cotyledonary effect on growth with respect to sterol biosynthesis. PMID- 7791533 TI - Side-chain oxysterol regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. AB - Side-chain oxysterols are known to be potent inhibitors of 3-hydroxy-3 methylglutaryl CoA reductase, a key regulatory enzyme in the biosynthesis of sterols. Structural variations in the side-chain oxysterols influence enzyme inhibition. Under certain conditions, biological systems have been induced to produce side-chain oxysterols, adding support to the hypothesis that oxysterols may be natural regulators of sterol biosynthesis in the intact cell. Specific inhibition of sterol biosynthesis is of interest as it may prove useful in the prevention or reversal of various cardiovascular disease states, as well as in the control of normal and abnormal cell growth. PMID- 7791535 TI - Biosynthesis and distribution of insect-molting hormones in plants--a review. AB - Insect-molting hormones, phytoecdysteroids, have been reported to occur in over 100 plant families. Plants, unlike insects, are capable of the biosynthesis of ecdysteroids from mevalonic acid, and in several cases the biosynthesis of phytoecdysteroids was also demonstrated to proceed via sterols. Spinacia oleracea (spinach) biosynthesizes polypodine B and 20-hydroxyecdysone, which is the predominant insect-molting hormone found in plant species. The onset of ecdysteroid production in spinach requires the appropriate ontogenetic development within the plant, which is related to leaf development. In spinach, lathosterol is the biosynthetic precursor to ecdysone and 20-hydroxyecdysone. Phosphorylated ecdysteroid intermediates, particularly ecdysone-3-phosphate, are required during biosynthesis. Polyphosphorylated forms of ecdysteroids are putative regulatory components of the pathway. During spinach development, the 20 hydroxyecdysone is transported from the sites of biosynthesis to the apical regions. An analysis of the physiological data available suggests that different species may synthesize ecdysteroids in various organs and distribute these ecdysteroids to other sites. Annual plants appear to concentrate ecdysteroids in the apical regions, including flowers and seeds. Perennial plants may recycle their ecdysteroids between their deciduous and their perennial organs over the growing season. Further investigations of ecdysteroid biosynthesis and physiology within plants will be required before an acceptable system can be designed to test phytoecdysteroid effectiveness in vivo against insect herbivory. PMID- 7791536 TI - Sterol metabolism in the tobacco hornworm, Manduca sexta--a review. AB - A number of intermediates involved in the dealkylation and conversion of the major C28 and C29 phytosterols to cholesterol in insects were first isolated and identified in studies with the tobacco hornworm, Manduca sexta, carried out in our laboratory. We also investigated the effects of a variety of known sterol metabolism inhibitors in Manduca, particularly those affecting the delta 24 sterol reductase enzyme, and synthesized and tested a number of new inhibitors as well. In-depth studies of ecdysteroids in Manduca during embryogenesis and during pupal-adult development provided new information on molting hormone content, biosynthesis, and metabolism. In addition, this insect has been utilized in the study of three specific enzyme systems of ecdysteroid metabolism, namely 20 monooxygenase, 3-epimerase, and phosphotransferase, which are critical to activation and deactivation of molting hormones in insects. PMID- 7791537 TI - Quantitation of steryl ferulate and p-coumarate esters from corn and rice. AB - The principal steryl ferulate and p-coumarate esters of different fractions from processed corn brans and corn oils, unrefined and refined, and from rice bran and rice bran oil were quantified by high-performance liquid chromatography. The results show that hexane-extracted corn oils yield more than five times the amount of esters compared to expeller processed oils. The yields of esters from bran and related products ranged from 0.07 to 0.54 mg/g of bran. Unrefined corn oils had levels from 0.18 to 8.6 mg/g for oil from hexane-extracted bran. By comparison, rice bran had ester levels of 3.4 mg/g of bran, and rice bran oil had levels of 15.7 mg/g of oil. The predominant esters from corn were sitostanyl and campestanyl ferulate, and sitostanyl and campestanyl p-coumarate. The principal esters from rice bran were cycloartenyl, 24-methylenecycloartanyl, and campesteryl ferulate. Rice bran oils had low levels of 24-methylenecycloartanyl but high levels of cyclobranol esters. The data presented provide a direct comparison of steryl ferulate and p-coumarate levels in the two cereals, and will aid in selecting the most suitable sources for the isolation of these compounds from corn products. PMID- 7791538 TI - Endotoxin inactivating action of plasma in patients with liver cirrhosis. AB - The endotoxin inactivating action of plasma was evaluated in 62 patients with cirrhosis and 10 healthy subjects. Endotoxin from E. coli 0111:B4 was added to each plasma sample to a final concentration of 250 pg/ml and the percentage loss of endotoxin activity by incubation (37 degrees C for 1 h) was calculated as the endotoxin inactivating rate. The plasma endotoxin inactivating rate in cirrhotics was significantly greater than that in healthy subjects, although patients with Child C cirrhosis and marked hyperbilirubinemia had a significantly lower endotoxin inactivating rate than other cirrhotics. The plasma endotoxin inactivating rate was positively correlated to serum HDL-cholesterol levels. In patients with Child A and Child B cirrhosis, the endotoxin inactivating rate was positively correlated to the endotoxin binding capacity of plasma albumin. The present results support the assumption that the plasma of cirrhotics has a high endotoxin inactivating capacity. Its decrease may augment endotoxicity in patients with advanced liver cirrhosis. PMID- 7791539 TI - Testing for hepatitis C virus sequences in peripheral blood mononuclear cells of patients with chronic hepatitis C in the absence of serum hepatitis C virus RNA. PMID- 7791540 TI - Dose-related opposite effects of hydrocortisone on hepatocyte proliferation in the rat. AB - To evaluate the role of glucocorticoids in the regulation of hepatocyte proliferation, high doses (6.25 mg/kg or more) and low doses (1.25 mg/kg or less) of hydrocortisone were injected into various categories of rats which had very different levels of proliferation. We used: (a) suckling rats whose stable unsynchronized proliferation can be stimulated and synchronized by acute inflammation or cyproterone feeding; (b) adult rats with a low level of proliferation, and (c) 2/3 hepatectomized rats during the first period of synchronized proliferation or during the second period of lower and unsynchronized proliferation. The kinetics of the labelling index and mitotic index were observed after hydrocortisone injection. High doses inhibited proliferation, as already found by many investigators. This effect was observed in suckling and hepatectomized rats and during acute inflammation in suckling or adult rats. Low doses had no inhibitory activities and, on the contrary, stimulated proliferation in some situations. The highest stimulations were observed during the early period after 2/3 hepatectomy or in combination with acute inflammation either in suckling rats or in 2/3 hepatectomized rats during the late period of regeneration. In all these situations hydrocortisone was a cofactor active during the early G1-phase. In contrast, in normal suckling rats a slight stimulation was observed due to an action at the G0-G1 transition. No such effect was found in adult rats. Our data show that doses of hydrocortisone in the therapeutic range or close to physiological values do not inhibit and, on the contrary, can stimulate hepatocyte proliferation. PMID- 7791541 TI - Prediction of prognosis of primary biliary cirrhosis in Japan. AB - The clinical profile of primary biliary cirrhosis in Japan was clarified on the basis of data on 1066 patients attending 212 hospitals and institutions in this country. Six hundred and twelve patients (57.4%) were asymptomatic. The majority of the patients were middle-aged women. Pruritus was the most frequent initial symptom of symptomatic primary biliary cirrhosis. Antimitochondrial antibodies were positive in 877 patients (82.5%). Sjogren's syndrome was the most common associated autoimmune disease. Liver biopsy was performed in 753 patients at the time of diagnosis, and histological staging by Scheuer's classification indicated that 307 (43.7%) patients were in stage I and 222 (31.6%) were in stage II. The most frequent causes of death were hepatic failure and/or gastrointestinal bleeding, which affected 166 (78.3%) of the 212 patients who died. Statistical analysis using Cox's regression method revealed that the patient's age and the serum bilirubin, albumin, and total cholesterol concentrations were significant predictors of the prognosis. A prognostic index was also calculated that could be used to predict the duration of survival for patients with primary biliary cirrhosis. PMID- 7791542 TI - Type VI collagen gene expression in experimental liver fibrosis: quantitation and spatial distribution of mRNAs, and immunodetection of the protein. AB - Type VI collagen is a minor but essential matrix component in the liver. In this study, we utilized an acute and a chronic injury model to clarify the process of liver fibrosis in rats by administration of carbon tetrachloride. Collagen gene expression, with particular emphasis on type VI collagen, was studied by molecular hybridization techniques. The alpha 2(VI) collagen mRNA levels were markedly elevated on day 3 of acute injury and were approximately at the same high level at 7 and 14 weeks of chronic injury, as determined by Northern hybridizations and slot-blot analyses. Marked enhancement of type I collagen gene expression was similarly noted at these time points. The activation of collagen gene expression in acute injury, as determined by in situ hybridization, was particularly prominent in the vicinity of the central veins. Indirect immunofluorescence demonstrated marked accumulation of type VI collagen protein as early as day 3 of acute injury, and the reaction appeared to be initiated in the proximity of central veins. These results indicate that type VI collagen gene expression, together with other connective tissue components, including type I collagen, is activated in the early stages of the fibrotic process. Type VI collagen accumulation may contribute to the distorted architecture and functional impairment of the liver in hepatic fibrosis. PMID- 7791543 TI - Cytochemical detection of a class 3 aldehyde dehydrogenase in human hepatocellular carcinoma. AB - The development of hepatocellular carcinoma in rodents treated with different chemical compounds is associated with the appearance in the cytosol of neoplastic liver cells of an unusual aldehyde dehydrogenase isozyme of class 3 (ALDH-3) which is very active with aromatic aldehydes. This tumor-associated isozyme is readily detected by enzyme cytochemistry using the substrate benzaldehyde with NADP as coenzyme. To determine whether human hepatocellular carcinomas express ALDH-3, the activity of this isozyme was examined in frozen sections from 68 echo guided human liver biopsies. In 54 cases the guided biopsy was performed on one or more nodules suggestive for hepatocellular carcinoma found at ultrasonography within the liver parenchyma. The remaining 14 patients were affected by chronic active hepatitis or cirrhosis. An intense enzymatic activity was ascertained in 5 out of 36 hepatocellular carcinomas. In non-neoplastic liver, in macroregenerative nodules and in metastatic adenocarcinomas enzymatic activity was not detectable. ALDH-3-positive tumors were typical hepatocellular carcinomas (histological grade II and III). These results suggest that ALDH-3 is a phenotype associated with malignancy in human liver tumors. PMID- 7791545 TI - MRI segmentation: methods and applications. AB - The current literature on MRI segmentation methods is reviewed. Particular emphasis is placed on the relative merits of single image versus multispectral segmentation, and supervised versus unsupervised segmentation methods. Image pre processing and registration are discussed, as well as methods of validation. The application of MRI segmentation for tumor volume measurements during the course of therapy is presented here as an example, illustrating problems associated with inter- and intra-observer variations inherent to supervised methods. PMID- 7791544 TI - Liver disease and serum hexosaminidase levels. Studies in a human hepatoma cell line (Hep G2 cells). AB - In various forms of liver disease, increased levels of the lysosomal enzyme beta hexosaminidase (Hex) occur in serum. This may be caused by disturbances of the hepatocytic function, and we therefore studied the intracellular and extracellular isoenzyme pattern of Hex in a human hepatoma cell-line (Hep G2), using an immunoassay method, which separates Hex A and Hex B isoforms. This cell line synthesizes and secretes Hex. The cumulative release of extracellular activity was about 3-10% of the intracellular activity. B-isoforms comprised one third of intracellular activity but only 20% of extracellular activity. The proportion of extracellular B-isoforms increased with time, presumably due to instability of A-isoforms at 37 degrees C. Cycloheximide inhibited the release of Hex activity, whereas NH4Cl increased the extracellular fraction of Hex, even at a concentration of 1 mmol/l. We speculate that the increased concentration of NH4+ in patients with liver disease interferes with the distribution pathway of the lysosomal enzymes. This might be one reason for the increased serum Hex activity found in patients with liver disease. PMID- 7791546 TI - Blue blood or black blood: R1 effects in gradient-echo echo-planar functional neuroimaging. AB - Changes in the longitudinal relaxation rate (R1) may play a role in the MRI signal intensity increases that have been associated with physiological brain activation. We used gradient-echo echo-planar MRI (GRE-EPI) to test whether physiological activations associated with hypercapnia in dogs were dependent on the delay (TR) between successive images in a time-series. Our results show that, in addition to activation-induced changes in the R2 (transverse relaxation including inhomogeneity effects), activation-induced changes in R1 are significant under certain pulsing conditions. In our paradigm, the R1 contribution became significant at TR values of 1 s or less. PMID- 7791547 TI - Spin-lattice relaxation and magnetization transfer in intracranial tumors in vivo: effects of Gd-DTPA on relaxation parameters. AB - Spin-lattice relaxation time T1 and relaxation parameters in magnetization transfer (MT) imaging were measured in 11 intracranial tumors before and after injection of Gd-DTPA at 0.1 T by using the inversion recovery method and the saturation transfer technique, respectively. Preinjection T1 relaxation times of the tumors were longer than those of white matter, but after Gd-enhancement the relaxation times of most tumors were in the same range as those of white matter. Gd-DTPA shortened the apparent relaxation time in the presence of off-resonance saturation pulse (T1a) due to marked shortening of the relaxation time of mobile water (T1w). Gd-DTPA decreased the magnetization transfer contrast (MTC) but did not influence on the magnetization transfer rate (Rwm). The parameters MTC and Rwm differed clearly between Gd-enhanced tumors and normal brain, whereas the relaxation time T1a was in many Gd-enhanced tumors in the same range as in normal brain. PMID- 7791548 TI - Value of Gd-DTPA-enhanced MR imaging of the labyrinth in patients with sudden hearing loss. AB - Recent reports describe labyrinthine enhancement on MRI as a highly specific sign of labyrinthine disease. This paper reports 44 patients with unilateral sensorineural hearing loss (SNHL) and laboratory evidence of cochlear damage investigated with Gd-enhanced MR imaging. Enhancement of the cochlea was observed in only one patient with a lesion at the fundus of the internal auditory canal (IAC) that extended into the cochlea after Gd-DTPA administration. In one more patient, MR imaging demonstrated large vestibular aqueducts as underlying cause for his hearing loss, but no enhancement of the labyrinth was observed. No abnormal signal intensity on precontrast MR scans nor pathologic enhancement of the membranous labyrinth were identified in the other 42 patients. Gd-enhanced MR imaging appears to be insensitive in demonstrating labyrinthine disease and normal examination findings in a patient with sudden SNHL cannot exclude damage at the cochlear level. PMID- 7791549 TI - Superparamagnetically labelled neutrophils as potential abscess-specific contrast agent for MRI. AB - In order to evaluate the potential of superparamagnetically labelled neutrophils as inflammation-specific contrast agents for magnetic resonance imaging (MRI), various types of magnetite particles were associated with isolated human neutrophils in vitro and subsequent effects on characteristic cellular functions investigated. Exposure to uncoated magnetite caused strong irreversible cell aggregation, whereas uptake of polystyrene-embedded magnetite microcrystals (Estapor M1-0.70/60) occurred with only minor changes in neutrophil adhesion properties, cellular metabolism, and chemotactic behaviour in vitro. As revealed by MR phantom imaging, Estapor-labelled neutrophils generated visible contrast above a threshold concentration of 1-2 micrograms Fe/g in a tissue-equivalent environment. Intravenous administration of labelled neutrophils to rabbits resulted in local magnetite accumulation up to 2.4 micrograms Fe/g tissue in artificial inflammation sites. Subsequent T2-weighted imaging of an intramuscular abscess clearly demonstrated the expected hypointense area surrounding the typically bright core of inflammation. PMID- 7791551 TI - High resolution MR imaging of joint degeneration in the knee of the STR/ORT mouse. AB - MR imaging of the knee joints of the mouse at 2.35 T produces an in-plane resolution of 35 x 70 microns and a slice thickness of 600 microns from the sagittal and coronal planes, in less than 60 min. In normal, live DBA mice, which have no known pathology, the images clearly resolve many joint structures, such as the cruciate ligaments, menisci, and articulating surfaces of the femur and tibia. Gross pathological changes were identified first in excised knees from cadaver mice of the STR/ORT strain. Males of this strain spontaneously exhibit rapid joint degeneration with increasing age compared to females, in which much milder symptoms develop more slowly. Thickening of the patellar tendon, displacement of the patella, deformity, and sclerosis were clearly distinguishable in males compared with females older than 7 mo of age. The same degenerative features were evident in MR images of the knees of the live male but not female STR/ORT mice of this age, indicating that it would be possible to monitor longitudinally by MR imaging progressive development of joint changes in this osteoarthritic model. PMID- 7791550 TI - Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents. AB - Macroscopic protonation constants were measured for a series of DTPA mono- and bis-amide ligands using potentiometric titrations. Proton NMR pH titrations yielded protonation populations of the various nitrogen and oxygen basic sites of the ligands for the different protonation stages. Amide formation decreased the basicity of the backbone nitrogens of the ligands and the thermodynamic stability of the corresponding Gd3+ chelates. Nuclear magnetic relaxation dispersion (NMRD) profiles and ESR linewidths were measured for the Gd3+ chelates. Some of these exhibited an elevated high field relaxivity relative to Gd(DTPA)2-, in response to their high molecular weight. As opposed to Gd(DTPA)2-, at 5 degrees C the chemical exchange process of the single inner-sphere water molecule of the bis amide complexes becomes so slow that it governs the paramagnetic relaxation process, causing the observed NMRD profiles to be close to those expected for the outer-sphere contribution. The chelates containing long alkyl side chains, such as Gd(DTPA-HPA2), showed increased relaxivity values in the presence of human serum albumin (HSA), indicative of noncovalent interaction with the protein. These chelates could be useful as nonionic hepatobiliary contrast agents. PMID- 7791552 TI - Temperature- and pH-dependence of proton relaxation rates in rat liver tissue. AB - In this study proton NMR relaxation rates R1 and R2 and pH of untreated fresh rat liver tissue as well as changes up to 4 h after tissue excision was investigated. Measurements were performed in the temperature range from 7 to 45 degrees C. Dynamic changes in all parameters were observed at higher temperatures (> or = 30 degrees C). A qualitatively different time course after tissue excision of all three parameters was obtained for 45 degrees C. The relative alterations like the change of relaxation rates referred to a reference value can predict tissue viability. A good correlation between R2 and pH in the range of 7-37 degrees C was detected and is described by an improved analytical model for R2 as a function of temperature and pH. The observed data lead to an empirical model given by R2 (pH,T) = 39.8 + (10.2 * delta pH) + (0.1 * delta T) + (0.2 * delta pH delta T), where the reference pH value was chosen 7.4 and the reference temperature value 37 degrees C (310.15 K), respectively. PMID- 7791553 TI - Magic-echo phase-encoding solid imaging with improved time resolution. AB - The magic-echo phase-encoding solid imaging (MEPSI) sequence is based on the magic-echo pulse sequence for the refocusing of the dipolar interaction and on pure phase-encoding for spatial resolution in all dimensions. MEPSI has many advantages; however, as a consequence of pure phase-encoding, it is very time consuming. In the following, two strategies are proposed to decrease the time necessary for the acquisition of an image by a factor of 2 per dimension. PMID- 7791554 TI - Quantitative NMR microscopy on intact plants. AB - Quantitative high resolution images on intact young maize plants were acquired by using magnetization-prepared NMR microscopy. Although the spatial resolution is low compared with that of light microscopy, the calculated spin density and T1 maps exhibit contrasts that are in excellent agreement with photomicrographic images. The T2 map gives image contrasts that are not visible in a usual light microscopic image. The diffusion images show an anisotropic behavior of the water self-diffusion coefficient in the vascular bundles, which can be understood by the cell morphology in this plant section. This work demonstrates that quantitative imaging on intact plant systems is possible and that long total acquisition times are no obstacle. Furthermore, the different single parameter maps give a better insight into the morphology of plants under in vivo conditions. PMID- 7791555 TI - Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease. AB - The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetylaspartate (NAA), creatine + phosphocreatine [Cr + PCr], and choline-containing metabolites (Cho) in the frontal part of the brain in 12 patients with probable Alzheimer's disease. Eight age-matched healthy volunteers served as controls. Furthermore, T1 and T2 relaxation times of the metabolites and signal ratios: NAA/Cho, NAA/[Cr + PCr], and [Cr + PCr]/Cho at four different echo times (TE) and two different repetition times (TR) were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. The concentration of NAA was significantly lower in the patients with probable Alzheimer's disease than in the healthy volunteers. No significant difference was found for any other metabolite concentration. For the signal ratios the only statistically significant difference was that the NAA/Cho ratio at TE = 92 ms and TR = 1.6 s was lower in the patients with probable Alzheimer's disease compared with the control group. A trend towards a longer T2 relaxation time for NAA in the patients with probable Alzheimer's disease than among the healthy volunteers was found, but no significant difference was found concerning the T1 and T2 relaxation times. PMID- 7791556 TI - A method for in vivo assessment of reversible rat pancreatic ischemia using 31P NMR spectroscopy at 2.0 tesla. AB - A surgical method is described which allows in vivo assessment of reversible rat pancreatic ischemia using 31P NMR spectroscopy at 2.0 T. Phosphorous-31 NMR spectra acquired during the ischemic period show the expected increase in inorganic phosphate with a concomitant decrease in ATP levels and pH as compared to controls. Upon reperfusion, inorganic phosphate and ATP returned to control levels while pH recovered to a more alkaline value. This method provides a means of studying in vivo changes in high energy metabolite associated with acute pancreatitis (AP) and maintains the secretory ability of the gland so that different forms of AP, such as those arising from pancreatic juice edema, can be studied. PMID- 7791557 TI - A method to distinguish between chemical shift and susceptibility effects in NMR microscopy and its application to insect larvae. AB - We propose a simple method of distinguishing Zeeman broadening arising from susceptibility inhomogeneity and chemical shift variation, applicable to NMR microscopy. The method is based on the use of a specially built probe-head in which orthogonal sample alignment is possible using the same radiofrequency (RF) coil. This allows the investigation of alignment effects in image distortion and relies on the fact that the isotropic chemical shift is invariant under reorientation, whereas the susceptibility-related local field will depend strongly on relative orientation of bounding surfaces with the external polarizing field. We apply this approach to the study of a simple phantom, and an insect larva (Spodoptera litura Fabricius), demonstrating in the latter case that susceptibility variations are sufficiently small to allow chemical shift imaging on a scale greater than 1 ppm. PMID- 7791558 TI - Value of RARE-MRI sequences in the diagnosis of lymphangiomatosis in children. AB - Three patients suffering from extensive cavernous lymphangiomatosis are presented here. They were examined by MRI using RARE-MR hydrography (rapid acquisition with relaxation enhancement) as well as conventional spin-echo sequences. RARE sequences, which depict each fluid-filled lymphatic space, can be used for screening. RARE-sequences help to shorten investigation time, particularly in cases involving the skeleton. The imaging strategy can be changed according to the results of this sequence. It may be performed prior to spin-echo sequences and facilitates follow-up investigations. RARE sequences distinguish between lymphangiomatosis and hemangiomatosis, or a combination of the two. PMID- 7791559 TI - Proton MRS similarity between central nervous system non-Hodgkin lymphoma and intracranial tuberculoma. AB - Proton magnetic resonance spectroscopy (MRS) was carried out on a patient with histologically proven non-Hodgkin lymphoma (NHL) of the central nervous system (CNS). The observation of the presence of a huge resonance in the region between 0.5-1.5 ppm and the absence of any other signals is not in agreement with those published for NHL in the literature but has a striking similarity to that reported for an intracranial tuberculoma. PMID- 7791560 TI - 31P (MRS) changes as a measure of therapy response in human osteosarcomas implanted into nude mice. PMID- 7791562 TI - [Skin impedance and analogue bridge devices for its measurement]. AB - Principal opportunities of the impedance method in relation to studies of the skin electrical properties are shown. Two devices varying in functional capacities are proposed which are inferior to the known models in simplicity and range of functions. These devices are based on bridge schemes and transform parameters of electrical resistance of the skin into the analogue signals. PMID- 7791564 TI - [Automated administration system of the Samara Diagnostic Center]. PMID- 7791561 TI - [Instruments for the development of dialogue interfaces in medical computer systems]. PMID- 7791565 TI - [Structural organization of medical information as illustrated by diagnosis in child neurology]. AB - Structuration of medical information is performed on three levels: structuration of the specialist's knowledge with resultant singling out key questions--blocks required for diagnosis in the given field; structuration of signs within the space of the blocks; identification of diagnostic syndromes basing on their signs analysis adjusted to resolving diagnostic tasks. The results of the method application in neuropathology are outlined. PMID- 7791563 TI - [New high-strength corrosion-resistant steel for medical instruments]. AB - New high-strength corrosion-resistant steel based on ageing martensite, metastable and stable austenite intended for the production of medical instruments for different purposes are considered. There are data on changing mechanical properties of corrosion-resistant steel and their dependence on thermoplastic treatment condition. PMID- 7791566 TI - [Current methods and equipment in densitometry of the bone tissue]. AB - In the past 15 years there has been an intensive development of methods and equipment for non-invasive quantitative determination of the mineral status of the human skeleton in the USA and some Western European countries. The specialized osseous densitometers which are based on photon absorptiometry and which use various radionuclides or an X-ray tube as a source of radiation have extensively spread. PMID- 7791571 TI - [Three models of eyeglass test frames]. AB - The paper presents a technical, medical and economic rationales for the expediency of simultaneous manufacture of three models of present-day test spectacle frames, such as general-purpose, semiframe, and simplified semiframe ones, which will provide their rational, methodological and the most efficient use in choosing corrective spectacles in relation to the complexity of chosen vision correction. PMID- 7791567 TI - [Development of dental radiography equipment]. PMID- 7791568 TI - [Problems of updating x-ray diagnosis departments]. PMID- 7791570 TI - [Present-day systems of programmed bases of electrophysiological studies]. PMID- 7791572 TI - [Image analysis of ECG rhythm]. AB - The paper deals with ECG rhythmic structure presentation oriented on image thinking of the specialist making diagnostic decisions in interactive interaction with computer. Rhythmogram complex for personal computer is designed. PMID- 7791569 TI - [ELEMAGS apparatus and clinical experience in its use in the treatment of children with hypoacusis and otalgia]. AB - To enhance effectiveness of magnetotherapy in the treatment of otic diseases the authors propose to use impulse low-frequency electromagnetic field in combination with constant magnetic field. ELEMAGS equipment based on the above principles is introduced to treat cochlear neuritis and neurosensory hypoacusis in children. PMID- 7791573 TI - American College of Sports Medicine position stand. Osteoporosis and exercise. AB - Osteoporosis is a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Both men and women are at risk for osteoporotic fractures. However, as osteoporosis is more common in females and more exercise related research has been directed at reducing the risk of osteoporotic fractures in women, this Position Stand applies specifically to women. Factors that influence fracture risk include skeletal fragility, frequency and severity of falls, and tissue mass surrounding the skeleton. Prevention of osteoporotic fractures, therefore, is focused on the preservation or enhancement of the material and structural properties of bone, the prevention of falls, and the overall improvement of lean tissue mass. The load-bearing capacity of bone reflects both its material properties, such as density and modulus, and the spatial distribution of bone tissue. These features of bone strength are all developed and maintained in part by forces applied to bone during daily activities and exercise. Functional loading through physical activity exerts a positive influence on bone mass in humans. The extent of this influence and the types of programs that induce the most effective osteogenic stimulus are still uncertain. While it is well-established that a marked decrease in physical activity, as in bedrest for example, results in a profound decline in bone mass, improvements in bone mass resulting from increased physical activity are less conclusive. Results vary according to age, hormonal status, nutrition, and exercise prescription. An apparent positive effect of activity on bone is more marked in cross-sectional studies than in prospective studies. Whether this is an example of selection bias or differences in the intensity and duration of the training programs is uncertain at this time. It has long been recognized that changes in bone mass occur more rapidly with unloading than with increased loading. Habitual inactivity results in a downward spiral in all physiologic functions. As women age, the loss of strength, flexibility, and cardiovascular fitness leads to a further decrease in activity. Eventually older individuals may find it impossible to continue the types of activities that provide an adequate load-bearing stimulus to maintain bone mass. Fortunately, it appears that strength and overall fitness can be improved at any age through a carefullly planned exercise program. Unless the ability of the underlying physiologic systems essential for load-bearing activity are restored, it may be difficult for many older women to maintain a level of activity essential for protecting the skeleton from further bone loss. (ABSTRACT TRUNCATED) PMID- 7791575 TI - Osteomyelitis of the pubic symphysis in athletes: a case report and literature review. AB - Groin pain is a common problem in athletes. Osteitis pubis, a chronic inflammatory condition involving the pubic symphysis, is a rare cause, and pyogenic osteomyelitis of the pubis is seen even more rarely in healthy athletes. We report one of four cases of pyogenic osteomyelitis of the pubis seen at our institution, review our experience with all four cases, and present a review of the literature (7 cases). The diagnosis is established by the presence of extreme pain, point tenderness at the pubic symphysis, fever, and either a positive culture of blood, needle aspiration, or open biopsy of the pubis. White blood cell count, erythrocyte sedimentation rate, and the results of bone scan and computerized tomography may initially be normal and therefore cannot exclude the diagnosis. Prompt treatment with intravenous (i.v.) antibiotics effective against Staphylococcus aureus (causative organism in all documented cases-9/11) should initially be administered and then guided by culture and sensitivity information. Oral antibiotics should be given if the infection is responsive to i.v. antibiotic treatment. Prompt recognition and treatment with antibiotics may obviate the need for surgical debridement. All athletes who returned to sports activity did so by 6 months after diagnosis. PMID- 7791574 TI - Effect of a newly designed patellar realignment brace on patellofemoral relationships. AB - The effect of applying a newly developed patellar realignment brace to a patient with lateral subluxation of the patella was evaluated using active movement, loaded kinematic magnetic resonance (MR) imaging. The brace corrected the lateral displacement of the patella as shown on the kinematic MR imaging study. The patient underwent physical rehabilitation in conjunction with the use of the patellar realignment brace and has had resolution of her painful symptoms for the past 4 months. PMID- 7791576 TI - Lipoprotein profile changes during intense training of Israeli military recruits. AB - The effect of prolonged strenuous military training on serum lipoproteins was studied in 73 new recruits. Dietary intake, body weight, and average energy expenditure were recorded, and blood samples collected at three time periods before training began (time 0), and after 6 and 12 wk of intense physical activity (times I and II, respectively). There was a significant increase in high density lipoprotein (HDL) cholesterol and a decrease in low density lipoprotein (LDL) cholesterol accompanying an increase of duration and intensity of exercise. HDL increased from 40.5 +/- 7.7 mg.dl-1 at time 0 to 44.5 +/- 9.4 mg.dl-1 at time I and to 52.8 +/- 8.7 mg.dl-1 at time II, and each mean P-value for increases in HDL from time 0-I, I-II, and 0-II were P < 0.0001). For LDL cholesterol, the mean decreases were -1.1, -6.1, and -7.3 mg.dl-1, respectively (P = 0.003 from I-II, and 0.01 from 0-II). These changes did not correlate with weight loss, reduced energy, or fat intake. We conclude that intense physical activity is associated with beneficial changes in the lipoprotein profile in new military recruits during a training period extending over 12 wk. PMID- 7791578 TI - Lipoprotein(a) [Lp(a)] levels in middle-aged male runners and sedentary controls. AB - Serum Lipoprotein(a) [Lp(a)] concentration was compared between middle-aged well trained Caucasian male endurance runners (N = 57), (mean age +/- SEM 47.8 +/- 0.7 yr) and age-, body mass-, and body mass index (BMI)-matched male nonathletic control subjects (N = 62), (mean age +/- SEM 48.7 +/- 0.8). The mean weekly training distance of the runners was (60.7 +/- 2.8 km.wk-1) at the time of testing. Median Lp(a) levels were not significantly different (P > 0.05) between the runners (15.0 mg.dl-1) and the control subjects (12.5 mg.dl-1). As expected, compared with control subjects, in runners levels of other lipoproteins and apoproteins were significantly more favorable for cardiovascular health (all P < 0.01). There was no significant relationship between Lp(a) and any other measured variable (lipid, anthropometric, or dietary) in the runners group. In the control group, the significant positive correlation between Lp(a) and LDL-C was no longer significant after correction for the estimated contribution of Lp(a) cholesterol to LDL-C. These cross-sectional data suggest that a lifestyle of moderate to intense exercise training does not exert a significant impact on the Lp(a) level. PMID- 7791577 TI - A physical conditioning program does not alter fibrinogen concentration in young healthy subjects. AB - Twenty five subjects were divided into experimental (N = 13, 7 male and 6 female, age 32.1 +/- 6.4 yr) and control groups (N = 12, 6 male and 6 female, age 33.4 +/ 5.4 yr) in order to examine the effect of a conditioning program on fibrinogen concentration. Before and after conditioning, VO2max was determined in all subjects. The experimental group (E) exercised for 30 min, 3 d.wk-1 for 12 wk at 70% (initial 6 wk) and 80% (latter 6 wk) of maximum heart rate. The control group (C) maintained normal activity pattern. After conditioning, subjects in E, but not in C, increased (P < 0.001) their VO2max. Resting fibrinogen concentrations (RFC) before conditioning were similar between the two groups, and demonstrated no change in the C group (242.9 +/- 40.3 mg.dl-1 vs 247.4 +/- 38.7 mg.dl-1, P > 0.05) after conditioning. Although RFC showed a 6% decrease in the E group post conditioning (249.1 +/- 21.5 mg.dl-1 vs 236.4 +/- 34.6 mg.dl-1), this decrease was not significant (P > 0.05). A significant increase (P < 0.05) in fibrinogen concentrations were observed after maximal exercise in both groups pre and post conditioning; however, this increase disappeared (P > 0.05) when data were corrected for hemoconcentration. These results suggest that after conditioning the 6% decrease in RFC was not statistically significant, but the possibility of Type II error is high. PMID- 7791579 TI - Guidelines, standards, and perspectives in exercise immunology. AB - Exercise immunology is a rapidly developing subdiscipline of sports science. Although many interesting findings have been published, some conflicting data have appeared. This is not surprising given the complexity of the immune system and its bidirectional interactions with other physiological systems. Immune measurements can also be influenced by age, gender, lifestyle, and biological rhythms while technical factors include leukocyte purification procedures, reagents, equipment, and assay conditions. Exercise-induced changes in the blood percentages of certain cell types may explain altered functional responses that may not change at the single cell level. Some guidelines should be established to limit the influence of these extraneous factors. Investigators should agree on fundamental methodology if work from different laboratories is to be compared and replicated. Given the rapid pace of new developments in fundamental immunology and related fields, some views on interpreting data in a wider physiological context and future research directions are discussed. Finally, some recommendations regarding subject selection, accounting for biological rhythms, standardizing fundamental methodology, sampling at multiple timepoints, and data analysis are put forward for discussion. Although uniform consensus would be impossible to obtain, hopefully this commentary will stimulate debate and lead to the formulation of some guidelines and standards for conducting studies in exercise immunology. PMID- 7791580 TI - Training suppresses hepatic lactate dehydrogenase activity without altering the isoenzyme profile. AB - A decrease in hepatic lactate dehydrogenase (LDH) activity following endurance training has been a consistent observation. In the present study, we sought to determine whether the training-induced decrease in hepatic LDH activity (pyruvate = substrate) was associated with a shift in the isoenzyme profile and/or alteration in other kinetic parameters. Animals (rats) were randomly assigned to either an endurance trained group (running 90 min at 30 m.min-1, 10% grade) or sedentary control group. Eight weeks of endurance training resulted in a significant decrease in maximal hepatic LDH activity for the forward reaction (pyruvate-->lactate), 107.3 +/- 5.5 mumol.min-1.g-1, when compared with control animals, 147.3 +/- 5.6 mumol.min-1.g-1. A similar decrease was observed for maximal LDH activity in the reverse reaction (lactate-->pyruvate), 49.8 +/- 2.1 vs 66.7 +/- 2.9 mumol.min-1.g-1, trained and controls, respectively. Training was also observed to decrease the Km for the reverse reaction, 5.18 +/- 0.78 mM vs 6.94 +/- 0.55 mM, for trained and controls, respectively. Km for the forward reaction was unaffected by training. Gel electrophoresis with densitometric evaluation revealed no shift in the isoenzyme pattern following endurance training. LDH5 accounted for 89% +/- 2%, whereas 6% +/- 0.5% was observed in LDH4, and 4% +/- 0.3% was observed in LDH3 for both groups. The densitometric area was approximately 34% lower from trained liver homogenates, a fractional decrease similar to that observed for maximal LDH activity. The decrease in hepatic LDH activity with endurance training appears attributable to a down regulation of enzyme content, with no significant alteration in isoenzyme distribution. PMID- 7791582 TI - Effects of running on the torsional strength, morphometry, and bone mass of the rat skeleton. AB - Intensity and duration effects of weight-bearing exercise on the rat skeleton were investigated. Eighty-four 3-month-old female Sprague-Dawley rats were assigned to control and nine exercise groups. Exercised rats were run on a treadmill for either 30, 60, or 90 min.d-1 at low (Vo2max approximately 55%), medium (VO2max approximately 65%), or high (VO2max approximately 75%) intensity 4 d.wk-1 for 10 wk. Rat femurs, tibias, and vertebrae were harvested for torsional mechanical tests, bone density assessment, and morphometry. Our results indicate exercise has a significant effect (P < 0.05) on the femoral mechanical response (energy absorbed and twist angle), tibial morphometry (cortical bone area and thickness), and tibial and vertebral bone density measurements but had no effect (P > 0.05) on bone strength when compared with control values. Higher intensity exercise decreased tibial and femoral torque (P < 0.05). Long duration exercise increased tibial and femoral stiffness and decreased twist angle and energy absorbed (P < 0.05). These results indicate bone adapts to its loading environment by increasing bone mineral density, increasing cortical bone area, increasing stiffness, decreasing energy absorbed, and decreasing twist angle. High-intensity exercise decreased the maximum force the bone could withstand, whereas long duration exercise made the bone more brittle. PMID- 7791581 TI - Skeletal muscle oxygenation during constant work rate exercise. AB - We compared the slow rise in VO2 during heavy exercise (i.e., greater than lactic acidosis threshold (LAT)) with changes in muscle oxyhemoglobin+oxymyoglobin (O2Hb/O2Mb) saturation by reflectance near infrared spectroscopy. Ten subjects performed four 6-min cycle ergometer tests with two constant work rates less than and two greater than the LAT, equivalent to 20, 40, 65 and 75% peak VO2. During less than LAT exercise, O2Hb/O2Mb saturation decreased to a minimum by 2 min and then remained constant or rose slightly. For greater than LAT work rates, the initial fall in O2Hb/O2Mb saturation was greater the higher the work rate and continued to decrease with time after 3 min. Between minutes 3 and 6, the rate of decrease in O2Hb/O2Mb saturation correlated with the increase in VO2 (r = -0.69, P < 0.0001). These studies support the hypothesis that the slow rise in VO2 during heavy constant work rate exercise is associated with a progressive decline in O2Hb/O2Mb saturation in the contracting muscles themselves that may be facilitated by capillary oxyhemoglobin dissociation owing to tissue lactic acidosis (Bohr effect). PMID- 7791583 TI - Arm crank exercise with static leg FNS in persons with spinal cord injury. AB - Persons with spinal cord injury experience considerable difficulty, during aerobic exercise, in achieving even moderate levels of oxygen uptake. Therefore, the effect of static functional neuromuscular stimulation (FNS) on this parameter during arm crank exercise (ACE) was investigated. Eight subjects with spinal cord injury, lesion levels range C6-T12, performed ACE at 60% and 80% of VO2peak, both with and without concurrent FNS of the lower limbs. ACE was performed with no FNS, with FNS at 40 milliamperes (mA), and with FNS at 80 mA. Significant differences in oxygen uptake were found between ACE without FNS and ACE with FNS 80 mA at 60% VO2peak (10% increase, 12.5 ml.kg-1.min-1 to 13.7 ml.kg-1.min-1, P < 0.05), and between ACE without FNS and ACE with FNS-80 mA at 80% VO2peak (16%, increase, 14.8 ml.kg-1.min-1 to 17.2 ml.kg-1.min-1, P < 0.01). A 10% difference between ACE without FNS and ACE with FNS-40 mA, did not reach significance. These data indicate that, in this population of subjects with spinal cord injury, (a) FNS can increase submaximal ACE oxygen uptake, and (b) that such increases are enhanced both at higher levels of FNS and of work load. Implications for wellness are discussed. PMID- 7791584 TI - Effects of an intensive 12-wk training program by elite swimmers on neutrophil oxidative activity. AB - The effects of an intensive 12-wk training program by 12 national-level swimmers on neutrophil oxidative activity were studied. Eleven sedentary (untrained) subjects (6 males and 5 females) served as environmental controls. Blood samples (10 ml) were taken at rest from an antecubital vein and neutrophils isolated by standard separation techniques. The oxidative burst activity of isolated neutrophils was assessed with an in vitro flow cytometric assay that used the fluorescent probe dihydrorhodamine 123. Two-way ANOVA (repeated measures) showed that oxidative activity was lower (P < 0.05) in the elite swimmers compared with the sedentary control group across the 12-wk period. Analysis of cells from swimmers in training was made: repeated measures ANOVA provided evidence of a significant decline (P < 0.05) in the number of cells responding positively ito in vitro challenge. Despite this decline, there was no significant difference in self-reported upper respiratory tract infection rate between the swimmers and sedentary individuals. These data show that: (i) elite swimmers undertaking intensive training have a significantly lower neutrophil oxidative activity at rest than do age- and sex-matched sedentary individuals; (ii) aspects of oxidative activity in swimmers are further suppressed during periods of strenuous training, and (iii) the extent of the suppression does not appear to be of clinical significance. PMID- 7791585 TI - Bone mineral density and dietary intake of female college gymnasts. AB - The purposes of this study were to determine bone mineral density (BMD) of female college gymnasts (N = 26) and age- (+/- 1.0 yr), height- (+/- 5.1 cm), and weight (+/- 2.3 kg) matched controls (N = 26) using dual energy x-ray absorptiometry and to examine the relationship of physical activity, diet, menstrual history, and BMD in these athletes. Energy expenditure, dietary intake and menstruation were assessed using standardized questionnaires. The BMD of the gymnasts were significantly (all P < 0.0001) higher than controls for the lumbar spine (L1-4), total proximal femur, femoral neck, Ward's triangle, and whole body. Mean calcium and kcal intakes for both groups were lower than the Recommended Dietary Allowances, and gymnasts had significantly lower kcal intakes than controls (P < 0.05). More gymnasts than controls (59% vs 24%) reported that their menstrual cycle had been interrupted at some point since menarche (P < 0.02). The major finding of this investigation is that the BMD of gymnasts were higher than matched controls despite the fact that gymnasts as a group had inadequate dietary calcium and a higher propensity to have an interruption of their menstrual cycle. PMID- 7791586 TI - Eating disorder symptoms in female college gymnasts. AB - In study 1, 21 females provided both honest and dishonest answers to the Eating Disorders Inventory-2 (EDI-2). It was found that the EDI-2 can be easily faked. The fake profile was used to screen subjects in a second study, in which 25 gymnasts and 25 matched controls were assessed on symptoms of eating disorders, energy intake, menstrual history, and bone mineral density (BMD). A Hotelling's T2 test (Wilks' lambda = 0.70) revealed that the gymnast and control groups did not differ significantly (P > 0.05) on the EDI-2 subscales; however, both groups exhibited scores on the Drive For Thinness (DFT) subscale of the EDI-2 that were higher than the published average for college women. More gymnasts (61%) than controls (24%) reported an absence of their menstrual cycle of 3 months or more. A higher percentage (8/11, 73%; chi 2 = 4.7, P < 0.05) of the subgroup with elevated DFT scores (i.e., > 14) reported having this disruption of their menstrual cycle compared with those with lower DFT scores (13/33, 39%). DFT scores were negatively (P < 0.05) related to energy intake (r = -0.48) and whole body BMD (r = -0.47). It is concluded that (a) DFT scores may be useful in identifying gymnasts at risk for problems associated with eating disorders, and (b) response distortion must be considered in future research using the EDI-2. PMID- 7791587 TI - Effects of stimulation intensity on the physiological responses of human motor units. AB - Quadriceps femoris muscles were studied in 50 healthy subjects to determine the physiological responses of the motor units recruited at different force levels during transcutaneous electrical stimulation. During one set of experiments force frequency relationships were compared at stimulation intensities that produced tetanic contraction of 20%, 50%, or 80% of the maximum voluntary isometric contraction (MVC). No differences in the normalized force-frequency relationship were observed between the 20% and 50% of MVC conditions and only a slight shift to the left was observed at 80% of MVC. The other set of experiments measured the responses to electrically elicited fatigue tests using frequencies of 20, 40, or 60 pps and, at each frequency, intensities that produced 20% or 50% of MVC. Fatigue was greater for the 50% than 20% MVC force conditions. Within each force level fatigue increased with increasing frequency. However, though the differences in the level of recruitment needed to produce the two forces varied for each frequency, the differences in the amount of fatigue produced at each force did not vary between the three stimulation frequencies. This suggests that the fatigue characteristics of the recruited motor units were similar at all intensities tested. We posit, therefore, that the physiological recruitment order during transcutaneous electrical stimulation is less orderly than previously suggested. PMID- 7791588 TI - Maximal voluntary quadriceps strength patterns in Olympic overtrained athletes. AB - Peak torques were studied in 10 elite male overtrained athletes and 10 controls matched for sex, age, sport, and performance level. Isokinetic concentric (CON) and eccentric (ECC) maximal voluntary contractions (MVC) of quadriceps muscle were assessed at the angular velocities of 60 degrees, 120 degrees, and 180 degrees.s-1. Sustained isometric MVCs were also measured at knee angles of 10 degrees, 45 degrees, and 80 degrees of flexion. Six seconds after the beginning of each isometric MVC, a 40-Hz electrical stimulation was superimposed on the MVC for a further 6 s. The overtrained subjects developed significantly smaller CON peak torques at 180 degrees.s-1 (P < 0.001), although ECC torques were similar at all three velocities. ECC/CON ratios were higher in the overtrained subjects at 120 degrees.s-1 (P < 0.01) and 180 degrees.s-1 (P < 0.001) compared with the controls. Isometric MVCs at 10 degrees and 45 degrees knee flexion were lower in the overtrained at P < 0.01 and P < 0.05, respectively. Also in the overtrained subjects, at knee angle of 10 degrees, the addition of the electrical stimulation to the isometric MVC produced an increase (P < 0.05) in torque levels. It is suggested that impaired central drive may account for the present findings. PMID- 7791589 TI - Effects of oxygen fraction in inspired air on rowing performance. AB - The present study examined the effect of oxygen fraction in inspired air (FIO2) on exercise performance and maximum oxygen consumption (VO2max). Six national level male rowers exercised three 2500-m all-out tests on a Concept II rowing ergometer. Each subject performed one test in normoxia (FIO2 20.9%), one in simulated hyperoxia (FIO2 62.2%) and one in simulated hypoxia (FIO2 15.8%) in a randomized single-blind fashion. The mean final rowing time was 2.3 +/- 0.9% (P < 0.01; 95% CI 1.4-3.2) shorter in hyperoxia and 5.3 +/- 1.8% (P < 0.01; 95% CI 3.1 7.5) longer in hypoxia when compared with normoxia. The effect of FIO2 on VO2max exceeded its effect on exercise performance as VO2max was 11.1 +/- 5.7% greater (P < 0.01; 95% CI 5.1-17.1) in hyperoxia and 15.5 +/- 3.2% smaller in hypoxia (P < 0.01; 95% CI 12.2-19.0) than in normoxia. Blood lactate concentration and O2 consumption per power unit (ml O2.W-1) failed to indicate statistically significant differences in anaerobic metabolism between normoxia and the other two conditions. These data suggest that there are other parameters besides those of energy metabolism that affect exercise performance as FIO2 is modified. These possible mechanisms are discussed in this paper. PMID- 7791590 TI - Wet suit effect: a comparison between competitive swimmers and triathletes. AB - The purpose of the present investigation was to examine the wet suit effect on 8 swimmers and 8 triathletes. For swimmers, the performances of a 400-m swim with and without wet suit were not statistically different (4 min 12.5 +/- 8 s vs 4 min 13.9 +/- 4 s) while for triathletes the swim times were reduced by 19 s (4 min 45.8 +/- 34 s vs 5 min 04.7 +/- 30 s, P < 0.01). For swimmers, VO2max and blood lactate measured with the wet suit were lower than without (P < 0.01), while for triathletes stroke rate was significantly higher with the wet suit (P < 0.01). For the whole group, the individual differences of performance were related to the blood lactate differences (r = -0.68; P < 0.01) and to the hydrostatic lift (r = 0.63; P < 0.01). For swimmers, the energy cost of swimming and the gliding ability were not statistically different with or without wet suit, while for triathletes they were significantly lower and decreased with velocity. It is concluded that the wet suit effect improves performance more in inefficient swimmers with low buoyancy, swimming at low speeds. PMID- 7791591 TI - Evaluation of body composition by dual energy x-ray absorptiometry and two different software packages. AB - Dual energy x-ray absorptiometry (DXA) measures body composition, tissue distribution, bone mineral content (BMC), and bone mineral density (BMD). Differences are possible due to software versions. This investigation examined body composition, tissue distribution, BMC, and BMD measurements using a DXA (Lunar Corp., Madison, WI) with different software packages (versions 3.4 and 3.6R). Fifteen women, ages 20-40 yr, enrolled in a weight-loss study (body mass index = 28) and volunteered for body composition assessment by densitometry. BMC, BMD, and tissue distribution measurements were made using DXA. Results were analyzed once each with software versions 3.4 and 3.6R. BMC + total soft tissue, measured using DXA, was comparable to measured body weight (3.4 = 76.3 kg; 3.6R = 76.5 kg; weight = 76.5 kg). Lower BMC and BMD (5.5% and 1.8%, P < 0.01) were observed with 3.6R. Arm tissue mass was lower (1,530 g; P < 0.01) and fat declined (1,069 g; P < 0.01) with 3.6R. Leg tissue mass decreased 487 g (P < 0.01), but fat tissue increased (526 g, P < 0.01) with 3.6R. A larger fat mass (1,492 g) and lower lean mass (1,115 g) were observed with 3.6R compared with 3.4. Percent fat values by densitometry using DXA 3.4 and 3.6R were 38.1%, 39.9, and 41.9%, respectively. These results demonstrated differences in total body composition, lean and fat tissue distribution, and bone measurements from DXA software versions. PMID- 7791592 TI - Combining event scores to estimate the ability of competitors. AB - Simulation was used to investigate the validities of nine measures of ability derived from scores of two or more competitive events. The measures were: raw means and least-squares means of raw scores, z scores, and normal scores; two measures derived from ranked scores; and the "personal-best" raw score. Simulations were performed for different numbers of competitors, events, and event entries, each for a range of validity of performance in a single event. A complete set of simulations was repeated for each of the following conditions: normal distribution of competitors' ability; skewed distribution of ability; event validity related to ability; validity, ability, and spread of scores differing between events; and events differing in difficulty. The raw mean of raw scores was generally the most valid measure. The personal best was comparable to the mean only when the number of entries approached one per competitor. The least squares mean of raw scores had highest validity when events differed substantially in difficulty; it should therefore be used when events differ in length, or when event scores are affected by environmental conditions, judging bias, or by uneven matching of competitors in match-play sports. PMID- 7791593 TI - Nonexercise regression models to estimate peak oxygen consumption. AB - The purpose of this study was to develop a VO2peak prediction model derived from nonexercise (N-EX) based predictors. VO2peak was measured using a walking treadmill protocol with 229 females and 210 males between 20 and 79 yr of age (mean +/- SD: 38.62 +/- 10.36 ml.kg-1.min-1). Subjects were randomly divided into validation (V) (85% of total; N = 374) and cross-validation (CV) (15% of total; N = 65) groups. The V group was used to validate generalized and gender-specific models using stepwise multiple regression procedures with gender, age and age2, percent body fat, and a physical activity code (AC). The generalized ml.kg-1.min 1 (R2 = 0.77, SEE = 4.90 ml.kg-1.min-1, SEE% = 12.7%) and gender-specific (females: R2 = 0.72, SEE = 4.64 ml.kg-1.min-1; males: R2 = 0.72, SEE = 5.02 ml.kg 1.min-1) models were highly accurate relative to N-EX and exercise based models in the literature. Cross-validation procedures were used to evaluate model stability. The generalized model was stable across the total CV group and various CV subsamples (by gender, decade-wide age groups, and AC groups), but not across groups similar in VO2peak. These results suggest that N-EX models can be valid predictors of VO2peak for heterogenous samples. PMID- 7791595 TI - PRESS-related statistics: regression tools for cross-validation and case diagnostics. AB - In the health science literature, a common approach of validating a regression equation is data-splitting, where a portion of the data fits the model (fitting sample) and the remainder (validation sample) estimates future performance. The R2 and SEE obtained by predicting the validation sample with the fitting sample equation is a proper estimate of future performance, tending to correct for the natural upward bias of the R2 and SEE obtained from fitting sample alone. Data splitting has several disadvantages, however. These include: 1) difficulty, arbitrariness, and inconvenience of matching samples; 2) the need to report two sets of statistics to determine homogeneity; and 3) the lack of equation stability due to diluted sample size. The PRESS statistic and associated residuals do not require the data to be split, yield alternative unbiased estimates of R2 and SEE, and provide useful case diagnostics. This procedure is easy to use, is widely available in modern statistical packages, but is rarely utilized. The two methods are contrasted here using a simulation from original data for predicting body density from anthropometric measurements of a group of 117 women. The PRESS approach is particularly appropriate for smaller datasets; methods of reporting these statistics are recommended. PMID- 7791594 TI - Energy expenditure during submaximal walking with Exerstriders. AB - This study was designed to determine whether Exerstriding, a modified form of walking using walking sticks (Exerstriders), resulted in an augmented cardiorespiratory response and a greater energy expenditure than when walking without Exerstriders. Female subjects (23.6 +/- 4.0 yr; 58.5 +/- 5.5 kg) completed two randomly assigned trials of treadmill walking (6.7 km.h-1; 0% grade; 30 min.) with (Exerstrider (E)) and without Exerstriders (Control (C)). Mean oxygen consumption (E = 20.5 +/- 1.2 ml.min-1.kg-1; C = 18.3 +/- 2.5 ml.min 1.kg-1), heart rate (E = 132.5 +/- 19.2 beats.min-1; C = 121.5 +/- 21.2 beats.min 1) and respiratory exchange ratio (E = .82 +/- .03; C = .78 +/- .04) were significantly greater (P < or = 0.05) while walking with Exerstriders. Total caloric expenditure was also significantly greater during the Exerstrider condition (E = 173.7 +/- 20.9 kcal; C = 140.7 +/- 27.2 kcal.). In contrast, the rating of perceived exertion did not differ significantly between the two conditions. These data suggest that Exerstriding provides a means to increase caloric expenditure during submaximal walking, a factor that may be of critical importance in enhancing health benefits--such as improved body composition and aerobic capacity--typically associated with walking programs. PMID- 7791596 TI - Visual distinctiveness can enhance recency effects. AB - Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed. PMID- 7791597 TI - Specificity of perceptual processing in rereading spatially transformed materials. AB - While most studies using the task of reading spatially transformed text do not reveal evidence of specific perceptual transfer, a study by Masson (1986, Experiment 3) provides clear evidence of such effects. Several experiments were designed to identify the basis for this empirical discrepancy. The only substantive evidence of specific perceptual transfer occurred when the words were presented in an unfamiliar typography, although each study suggested a trend toward perceptual specificity effects. The results are discussed in terms of Graf and Ryan's (1990) ideas about the role of distinctive memory representations. PMID- 7791599 TI - Decision strategies and visual-field asymmetries in same-different judgments of word meaning. AB - The accuracy with which observers judged whether two words belonged to the same semantic category was determined from a detection-theoretic analysis of same different judgments. In Experiment 1, one word was presented centrally and the other word in either the left visual field (LVF) or the right visual field (RVF); in Experiment 2, both words were presented to either the LVF or the RVF. In order to obtain receiver-operating characteristics (ROCs) of performance, observers were asked to rate their confidence that the two words belonged to the same semantic category. Two models of the decision strategy were fitted to the obtained characteristics: a differencing model, in which the decision variable was the difference between the two observations; and an optimal model, in which each observation was judged in relation to a criterion. In both experiments, the optimal model provided a better fit than the differencing model to the obtained characteristics. Maximum-likelihood estimates of both the criterion-free parameter, d', and the area under the operating characteristic, p(A), were greater for words presented in the RVF than for those presented in the LVF. PMID- 7791598 TI - Effects of association, frequency, and stimulus quality on naming words in the presence or absence of pseudowords. AB - According to classical dual-route theory, effects of associative priming and frequency on the naming of printed words arise from lexical access and should be weak or absent when word names are assembled prelexically. Assembled naming would be more likely in a shallow orthography, especially in the presence of nonwords. This hypothesis was examined with the shallow Serbo-Croatian orthography. Interactions between association, frequency, and stimulus quality were also examined in both Serbo-Croatian and English. Contrary to classical dual-route theory, both lexical effects were found for naming words in Serbo-Croatian, with or without nonwords. Neither interaction was significant in Serbo-Croatian and only association x quality was significant in English. Discussion focused on (a) the claim that lexical effects on naming in a shallow orthography constitute prima facie evidence against either prelexical phonology or the orthographic depth hypothesis, and (b) the possible factorization of frequency and active associative knowledge in naming words. PMID- 7791601 TI - Recollective experience in the revelation effect: separating the contributions of recollection and familiarity. AB - The revelation effect is a phenomenon of recognition memory in which words presented for a recognition decision are more likely to be identified as previously studied if they are initially disguised and are then somehow revealed to the subject. The goal of the present experiments was to determine whether the revelation effect has similar or different influences on the conscious recollection of a previous encounter with a test item and on the feeling of familiarity evoked by a test item. The process-dissociation procedure (Experiment 1) and the remember/know procedure (Experiment 2) were used to achieve this goal. The main findings of these experiments were that revealing an item at test (1) increased the feeling of familiarity associated with that item, especially if it was not previously studied, and (2) decreased conscious recollection of previously studied items. These data narrow the range of potential explanations of the revelation effect. PMID- 7791600 TI - Pronominalization and discourse coherence, discourse structure and pronoun interpretation. AB - Two self-paced reading-time experiments are reported that examine the time course of pronoun interpretation processes based on local discourse structure and on world knowledge. The characterization of local discourse structure is based on recent work on centering, which provides a specific formulation of how the ways in which sentences make reference to common entities determines the coherence of discourse segments and how discourse structure influences interpretation of ambiguous pronouns. The results of the first experiment show that readers generate a default interpretation of a pronoun based on features of local discourse structure, and that that default interpretation is later confirmed or overridden by knowledge-based processes. The results of the second experiment show that local discourse structure continues to influence pronoun interpretation even when the semantic information that ultimately compels interpretation occurs before the pronoun. These results support the view that processes acting on local discourse structure play a powerful role in guiding language comprehension. PMID- 7791603 TI - Judging a book by its cover: interpretative effects of content on problem-solving transfer. AB - We examine how cover stories of isomorphic problems affect transfer. Existing models posit that people retain content in problem representations and that similarities and differences between the "undeleted" cover stories might interfere with recognition of structural similarities. We propose that cover stories can affect transfer in another way--by inducing semantic knowledge that modifies problem structures. Two experiments examined how people represent and solve permutation problems dealing with random assignment of elements from one set to elements from another set. Although the problems were structurally isomorphic, cover stories involving different pairs of element sets led subjects to abstract different "interpreted structures." Problems involving objects and people (e.g., prizes and students) led subjects to abstract an asymmetric structure ("get") and problems involving similar sets of people (e.g., doctors and doctors) led subjects to abstract a symmetric structure ("pair"). Transfer was mediated by similarities and differences between the interpreted structures of the learned and the novel problems. PMID- 7791602 TI - Essentialism and graded membership in animal and artifact categories. AB - A number of studies have argued that people view membership in animal and artifact categories as a matter of degree. These studies have generally failed to distinguish between the issues of typicality and category membership. Thus, data which have been taken to demonstrate that membership is a matter of degree may only demonstrate that typicality is graded. Partly on the basis of these findings, it has been argued that some categories are organized around an underlying essence. The essence determines membership absolutely. The present paper reports a series of studies that reexamine the question of graded membership. In the first study, subjects were asked to rate both typicality and category membership for the same stimuli as a way of distinguishing the two questions. A second method relied on the intuition that disagreements about membership in all-or-none and graded categories may have different qualities. Results from both studies suggest some support for claims that membership in animal and artifact categories is a matter of degree. A third study explored the possibility that graded responses were due to conflicting, or ambiguous, sets of criteria. A task focusing on biological features did not lead to more absolute categorization. These results contradict essentialist predictions. PMID- 7791605 TI - The diversity principle in the testing of arguments. AB - According to the diversity principle of scientific reasoning, hypotheses receive greater confirmation when they are supported by diverse rather than similar sets of data. This article examines whether people reason like intuitive scientists by conforming to the diversity principle in the testing of arguments. The results of two experiments demonstrate that people do indeed conform to the diversity principle by choosing a set of diverse rather than similar premises to test the conclusion of an argument. These findings are discussed in terms of the different reasoning processes involved in argument evaluation, argument testing, and rule discovery. PMID- 7791606 TI - Very rapid forgetting: reply to Cunningham, Healy, Till, Fendrich, and Dimitry. PMID- 7791607 TI - The effect of inflation on expenditures by mental health organization between 1969 and 1990. AB - At first glance, the rise in current dollar expenditures for all mental health organizations from $3.3 billion in 1969 to $28.4 billion in 1990 seems enormous. However, if the annual expenditures are adjusted for inflation and expressed in constant dollars, the rise in expenditures is only from $3.3 billion in 1969 to $5.6 billion in 1990. Thus, most of the increase in expenditures by mental health organizations over the past two decades is due to inflation, with less than 10 percent due to increases in real purchasing power. Since both the number of private psychiatric hospitals and the expenditures they incurred increased dramatically between 1969 and 1990, these hospitals showed gains in absolute dollar amounts and in dollar amounts per capita, even if the expenditures are expressed in constant dollars. To a lesser extent, the same was true of RTCs. Although both VA medical centers and State mental hospitals showed increases in expenditures as measured in current dollars, if expenditures are expressed in constant dollars, these organizations showed net decreases. Their inpatient populations also decreased during this period. However, if expenditures per inpatient under care are examined, the reverse is true. The per patient expenditures for State mental hospitals increased between 1969 and 1990, even if the results are stated in constant dollars.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791608 TI - Data highlights on: utilization of Mental Health Organizations by elderly persons. PMID- 7791604 TI - Reasoning about curvilinear motion: using principles or analogy. AB - People possess implicit theories about the motion of objects, theories that are often incorrect. When asked to predict the path of an object emerging from a curved tube, for example, people often say that the object will continue to follow a curved path. However, when solving a problem that reminds them of a familiar previous instance, people often reason by analogy to the instance. In this study, we show that a previous instance must be very superficially similar to a problem in order to be used as an analogy; otherwise, people will use their implicit theories as the basis of their reasoning. PMID- 7791609 TI - Reversible enzyme inhibitors as mechanistic probes. PMID- 7791610 TI - Kinetics of slow and tight-binding inhibitors. PMID- 7791612 TI - Product inhibition applications. AB - A product inhibition study provides important insight into the binding mechanism of an enzyme, especially in the identification of abortive complexes, but seldom is it the only tool required to solve the mechanism completely. Always keep in mind that more than one mechanism may be consistent with the patterns, and several alternative schemes should be analyzed by including abortive complexes and, as a last resort, isomerization steps or slow product release steps in the interpretation. Support for the proposed mechanism should be garnered from other data, such as kinetic studies with alternative substrates and competitive inhibitors, positional and molecular isotope exchange studies, binding studies, and isotope effects. A well-characterized binding mechanism complete with the identification of abortive complexes is even more important as rational drug design becomes more prevalent. Product inhibition studies represent an important tool that is relatively easy to apply to gain significant information about the binding mechanism of most enzymes. PMID- 7791613 TI - Kinetics of iso mechanisms. PMID- 7791611 TI - Kinetic method for determination of dissociation constants of metal ion nucleotide complexes. PMID- 7791614 TI - Mechanism-based enzyme inactivators. PMID- 7791615 TI - Transition state and multisubstrate analog inhibitors. PMID- 7791616 TI - Transient kinetic approaches to enzyme mechanisms. PMID- 7791617 TI - Partition analysis: detecting enzyme reaction cycle intermediates. PMID- 7791618 TI - Isotope effects: determination of enzyme transition state structure. PMID- 7791619 TI - Hydrogen tunneling in enzyme catalysis. PMID- 7791620 TI - Rapid quench kinetic analysis of polymerases, adenosinetriphosphatases, and enzyme intermediates. PMID- 7791621 TI - Positional isotope exchange as probe of enzyme action. AB - The positional isotope exchange technique has been found to be quite useful for the identification of reaction intermediates in enzyme-catalyzed reactions. For reactions where intermediates are not expected the method can be used with great utility for the quantitative determination of the partitioning of enzyme-product complexes. However, it must be remembered that it has been explicitly assumed that the functional group undergoing positional exchange is free to rotate. This assumption is not always valid since examples have been discovered where the functional group rotation is indeed hindered. For instance, in the reaction catalyzed by argininosuccinate synthetase a PIX reaction was not observed on incubation of ATP and citrulline even though a citrulline-adenylate complex has been identified from rapid quench experiments. PMID- 7791625 TI - Expression of properly folded catalytic antibodies in Escherichia coli. PMID- 7791624 TI - Proton transfer in carbonic anhydrase measured by equilibrium isotope exchange. PMID- 7791622 TI - Manipulating phosphorus stereospecificity of adenylate kinase by site-directed mutagenesis. PMID- 7791623 TI - Equilibrium isotope exchange in enzyme catalysis. PMID- 7791626 TI - Cooperativity in enzyme function: equilibrium and kinetic aspects. PMID- 7791627 TI - Kinetic basis for interfacial catalysis by phospholipase A2. PMID- 7791628 TI - Analysis of enzyme progress curves by nonlinear regression. PMID- 7791629 TI - Site-directed mutagenesis: a tool for studying enzyme catalysis. PMID- 7791630 TI - Effects of atrial natriuretic peptide on the unicellular Tetrahymena pyriformis model. AB - The vertebral hormone, atrial natriuretic peptide (ANP) has characteristic effects in Tetrahymena cells. ANP is able to induce the release of sodium ions, probably via the membrane rather than the contractile vacuole. The hormone is a potent inhibitor of Chinese ink-phagocytosis. A 10(-12) M concentration of ANP has the maximum positive effect on the division of cells but long-term treatments indicate the presence of a down-regulation-like mechanism. ANP has a strong chemoattractant characteristic between 10(-13) and 10(-11) M concentrations. Significant concentration dependent FITC-ANP binding at pretreatments of 10(-12) M suggest the presence of special receptor-dependent mechanisms which are responsible for the development of hormonal imprinting. The similarities between the most effective concentrations (10(-13) - 10(-12) M) and the human serum level of ANP shows that the effects of ANP have a more evolutionary background than previously considered. PMID- 7791631 TI - Effects of ciprofloxacin and vancomycin on physicochemical surface properties of Staphylococcus epidermidis, Escherichia coli, Lactobacillus casei and Lactobacillus acidophilus. AB - Under clinical conditions, during antibiotic treatment, micro-organisms often grow at sub-inhibitory concentrations. This may lead to altered adhesive cell surface properties and to a disruption of the indigenous microflora, in addition to the creation of a more pathogenic biofilm. The effects of growing Staphylococcus epidermidis, Escherichia coli and lactobacilli in the presence of sub-inhibitory concentrations of ciprofloxacin and vancomycin were determined. Growing the cells under antibiotic burden sometimes led to altered cell surface hydrophobicity (by adhesion to hexadecane), changes in the pH-dependence of zeta potentials, and elemental surface compositions or in different SDS-PAGE protein profiles. For several isolates only one of the surface properties was altered by the presence of an antibiotic in the growth medium and no systematic effects were observed for all isolates representing a certain species or even strain. The important conclusion to be drawn from the results of this study is that the effects of growing cells under antibiotic burden on their adhesive cell surface properties can only be established when using a variety of techniques. PMID- 7791632 TI - Partial purification and some properties of gamma-glutamyl peptide-hydrolysing enzyme from Actinobacillus actinomycetemcomitans. AB - A gamma-glutamyl peptide-hydrolysing enzyme was partially purified from Actinobacillus actinomycetemcomitans. The enzyme required metal ions, and 1 to 2 mM Mn2+ ions, especially, were essential for hydrolytic reaction. Its distribution by treatment of cells with lysozyme-EDTA suggested that the enzyme was a membrane-bound protein. The pI of the enzyme was in range of pH 5.1 to 5.6, and the apparent Km value for gamma-glutamyl-p-nitroanilide was 3.0 x 10(-4) M. The enzyme hydrolysed specifically gamma-glutamyl residues from the N-terminal of gamma-glutamyl compounds such as gamma-Glu-Met, gamma-Glu-Ala, gamma-Glu-Leu and gamma-Glu-Tyr, but did not catalyse the transpeptidation reaction. Neither free amino acids such as Ala-, Pro-, Gly- and Leu-p-nitroanilide nor alpha-glutamyl derivatives were hydrolysed. Its activity was strongly inactivated by metal chelators (EDTA or o-phenanthroline) and amino acids (Glu, Gln). In addition, the activity was specifically inactivated by gamma-glutamyl affinity-labelling reagents such as AT-125, 6-diazo-5-oxo-L-norleucine and azaserine, which are inhibitors of the gamma-glutamyl donor sites of mammalian gamma-glutamyl transpeptidase. Antibodies against bovine kidney gamma-glutamyl transpeptidase decreased the activity of the bacterial enzyme by 65%. These results suggested that the active sites in the bacterial enzyme were similar to those in mammalian gamma-glutamyl transpeptidase. PMID- 7791633 TI - Antitrust law applicable to managed care contracting. AB - Antitrust laws cannot be ignored by physicians on the basis that they are not fair, are too complicated or make no sense. The Justice Department and the FTC view independent practitioners as competitors. As such, organized actions by physicians relative to managed care contracting are carefully scrutinized for antitrust violations. A basic understanding of the antitrust laws is therefore essential. PMID- 7791634 TI - Jackson Physicians Alliance: making friends in the right places. PMID- 7791635 TI - Burns Clinic links up with national firm to tackle managed care. AB - The Burns Clinic Medical Center, PC, headquartered in Petoskey, has for many years been an innovator in state medical practice. Founded in 1931, the Burns Clinic today offers a range of medical and surgical services at eight sites in northern Michigan. With 120 physicians on staff and 550 support employees, the Burns Clinic is a major health care operation as well as a proven success. PMID- 7791636 TI - Corporate affiliated physicians. Who are they, and how are they likely to change the face of medicine in the years ahead? PMID- 7791637 TI - Change can be tough for physicians facing career move, retirement. PMID- 7791638 TI - The proper use of blood products. PMID- 7791639 TI - Wine, the tax man and alcohol-related disease. PMID- 7791640 TI - Molecular medicine makes its way to the bedside. Can medical practitioners afford to ignore the new DNA technology? PMID- 7791641 TI - Haemophilia A management in Victorian, New South Wales and South Australian haemophilia centres. AB - OBJECTIVE: To examine the management of haemophilia A in Australia and to compare it with international trends. METHODS: Six haemophilia centres treating most patients in Victoria, New South Wales and South Australia were surveyed in 1993 by means of a written questionnaire followed by an "on site" interview. RESULTS: The centres were treating 739 patients; 234 (32%) had severe haemophilia. Factor VIII inhibitors were present in 5.9% of all patients and in 19% of those with severe disease. Twenty-three per cent were human immunodeficiency virus (HIV) antibody-positive and 74% were hepatitis C virus (HCV) antibody-positive. The main treatment was "on demand" therapy for acute bleeds (average use of factor VIII: 1350 IU/kg per year for children; and 780 IU/kg per year for adults). Prophylactic therapy was used in only 17 patients, with doses of 3000-4500 IU/kg per year. One million IU was used for three patients with high titre inhibitors who had "tolerising" therapy. While most developed countries have a factor VIII supply of 2-5 IU per capita, the total supplied to the States represented 1.46 IU per capita, while use at the centres represented 1.1 IU per capita. CONCLUSION: Because supply of factor VIII is limited, use was less than half that recommended internationally. Shortage of factor VIII has compromised prophylactic therapy and virtually prevented "tolerising" therapy. PMID- 7791642 TI - Appropriateness of transfusions of red cells, platelets and fresh frozen plasma. An audit in a tertiary care teaching hospital. AB - OBJECTIVE: To determine how current hospital practice for transfusions of red cells, platelets and fresh frozen plasma conformed with published criteria. DESIGN: Elaboration of criteria for transfusion from a review of the current literature; and analysis of the medical records of patients receiving transfusions of red cells (200), platelets (215), and fresh frozen plasma (260) during defined time periods in 1993. SETTING: A large tertiary care teaching hospital. OUTCOME MEASURES: Inappropriateness rates for transfusion episodes and numbers of individual units of blood products administered. RESULTS: Inappropriateness rates for transfusion episodes and numbers of individual units administered were 16% and 10% for red cells, 13% and 11% for platelets, and 24% and 16% for fresh frozen plasma (31% and 21% when transfusions for thrombotic thrombocytopenic purpura were excluded). Red cells and fresh frozen plasma were used inappropriately most frequently in association with a surgical procedure; for platelets, it was their use for bleeding. In many of the transfusions deemed inappropriate, deficiencies of red cells, platelets and/or coagulation factors were documented, but the degree of deficiency did not meet the stringent appropriateness criteria. Twenty-six transfusions were deemed inappropriate because the indication was not documented in the medical record. CONCLUSIONS: Specific problem areas in which blood product use was inappropriate were identified. Guidelines for transfusion appropriateness, education of hospital staff, and a monitoring system to ensure adherence to the guidelines, are required. PMID- 7791645 TI - Laparoscopic cholecystectomy: its impact on national health economics. AB - OBJECTIVE: To assess whether sound economic reasons exist for the wider introduction of laparoscopic cholecystectomy in Australia. DESIGN: A retrospective survey of patients who underwent laparoscopic cholecystectomy. We compared time of hospital stay and time off work after laparoscopic cholecystectomy with data for open cholecystectomy. PATIENTS AND SETTING: Seventeen participating surgeons in four Australian States allowed access to patients treated between May 1990 and November 1991 (1254 patients in all). MAIN OUTCOME MEASURES: Patient acceptability of the procedure, average length of postoperative in-hospital stay, and the savings associated with earlier return to work compared with open cholecystectomy. RESULTS: Almost 90% of patients (1127) replied and 1088 responses were considered appropriate for analysis. Serious complications were rare; 96% of patients thought the technique was successful. The mean length of in-hospital stay was 2.6 days (range, 1-120), compared with a mean of 8.7 days for open cholecystectomy. Among working patients, the mean time to return to work was 11.6 days (range, 10.7-13.1), an estimated 27 days sooner than after open cholecystectomy. Extrapolating from these results, replacing 95% of open cholecystectomies with laparoscopic procedures would have 133,285 hospital bed-days and 500,000 work-days each year. CONCLUSION: Laparoscopic cholecystectomy is safe and effective. Its wider use in Australia would result in savings to both the individual and the national economy. PMID- 7791643 TI - Is wine the drink of moderation? AB - OBJECTIVE: To examine, in the light of a current national inquiry into taxation for wine, claims that wine drinkers rarely misuse alcohol and that cask wine is more likely to be misused than bottled wine. METHODS: 1272 persons aged 16 years and over and resident in metropolitan Perth were interviewed in their homes regarding their use of alcohol. RESULTS: The alcohol consumption of 524 (373 women, 151 men) who had drunk at least one glass of wine on one or more of their last four drinking days was examined in relation to National Health and Medical Research Council guidelines. While only 2.9% of women and 2.6% of men had an average daily intake of wine above low risk levels, 6.9% of women and 13.2% of men had exceeded these levels when considering all alcoholic beverages. When wine intake was examined for the day of highest consumption of the last four drinking days recalled by each respondent, 41.1% of women and 17.0% [corrected] of men had exceeded low risk levels. There was no significant difference in the amounts of cask and bottled wine consumed in 180 wine drinkers for whom the distinction between cask and bottled varieties could be made and who drank wine on their last drinking occasion. CONCLUSIONS: Past estimates of the contribution of wine consumption to excessive alcohol intake are underestimates. Raising the tax on wine should be considered as a public health measure and taxes should be levied in direct relation to alcohol content to encourage the consumption of lower alcohol varieties. PMID- 7791644 TI - The impact of firearm control legislation on suicide in Queensland: preliminary findings. AB - OBJECTIVE: To examine the effect of specific firearm control legislation on firearm and overall suicide rates. DESIGN: Retrospective survey of data from the Register of the Suicide Research and Prevention Program, Queensland Department of Health. The hypothesis was tested that the legislation would reduce firearm and overall suicides more in metropolitan and provincial city areas than in rural areas, where firearm ownership is higher. SETTING: State of Queensland 1990-1993. OUTCOME MEASURES: Suicide rates by age, sex and method for metropolitan, provincial city and rural areas in the two years before (1990-1991) and after (1992-1993) legislation. RESULTS: Mean annual firearm suicide rates declined significantly (P < 0.05) in metropolitan and provincial city areas after legislation (from 3.6 to 2.3 per 100,000 and from 5.2 to 3.1 per 100,000, respectively), with significant declines among men and in the 15-29 years age group. Rates increased slightly in rural areas (from 7.2 to 8.2 per 100,000). Overall suicide rates declined in provincial areas only, with minimal change in metropolitan areas and a slight rise in rural areas. CONCLUSION: These results provide preliminary evidence that firearm control legislation, including a 28-day "cooling-off" period before firearm purchase, reduces suicide rates, especially among younger adult men. PMID- 7791647 TI - Update on scleroderma. PMID- 7791646 TI - Three deaths from hemlock poisoning. PMID- 7791648 TI - Sleep problems. AB - Sleep complaints are common in the elderly, and are often related to physiological changes with ageing, or secondary to illness and drug therapy. Primary sleep disorders, such as sleep apnoea and movement disorders, are also common. Management should be specific to the problem. Attention to underlying factors and sleep hygiene, as well as reassurance and education about age-related sleep changes, will often be sufficient. Hypnotics, which usually offer only temporary symptomatic relief, may be counterproductive, and should be prescribed only in the short term, except in limited specific cases. Short-acting benzodiazepines (e.g., temazepam or oxazepam), or possibly zopiclone, are currently the drugs of choice. PMID- 7791649 TI - Accident victims as patients: moral obligation or negligence. PMID- 7791651 TI - Subungual desmoplastic melanoma in an aboriginal woman. PMID- 7791650 TI - Margarine--facts and myths. PMID- 7791652 TI - Public attitudes to smoke-free areas in sports venues. PMID- 7791653 TI - Approaching the NHMRC goal for second-dose measles-mumps-rubella vaccine uptake. PMID- 7791654 TI - Compliance with neonatal hepatitis B vaccination. PMID- 7791655 TI - Localised prostate cancer: which way forward? PMID- 7791656 TI - Suicidal behaviour in the Solomon Islands. PMID- 7791657 TI - Cataract extraction and Parkinson's disease. PMID- 7791658 TI - Rural practice--time to teach. PMID- 7791659 TI - So much written, so little said. PMID- 7791660 TI - [Evaluation of the socioeconomic status in epidemiological surveys: hypotheses of research in the Brianza area MONICA project]. AB - Socio-economic status (SES) has been reported as a causative factor of increasing health inequalities in industrialized countries. The phenomenon has been particularly investigated for job related diseases, including cardiovascular disease and risk. The group of occupational medicine specialists in the world wide MONItoring program of CARdiovascular disease (WHO-MONICA Project) is now producing a number of hypotheses about the application of internationally defined criteria and tools for SES evaluation in the Italian area of the Project, Area Brianza. After a short review of some main conceptual and methodological problems, a proposal is presented of an SES index, derived from the pooled data of two population surveys carried out in this area. From a randomized sample of 3200 residents, 25-64 years old, stratified by sex and age decade, 1731 subjects, 594 females and 1137 males, employed at the time of the screening were extracted. Four variables were considered: age, education, occupational level and job-strain (according to the Karasek-Theorell model) by which each subject was classified in three levels--high, medium, low--of education and occupation, whose combination was used to obtain as many levels of socio-economic status. This a method of building an SES index is based on a sequence of approximations following two essential criteria: limitation of the variables to be surveyed, through standardized procedures; ability to identify the "low" SES category, presumably more at risk for disease. PMID- 7791662 TI - [Organizational analysis of hospital work: identification of constraint elements and hypothesis of their relationship with nurses' wellbeing]. AB - The paper reports the results of a research project on hospital work in which the analysis of organized work situations in different contexts was made using a method based on a valid organizational theory, with the objective of an ergonomic study on the relationships between organized work and well-being. From the analysis of these different situations, via the application of the Method of Organizational Congruencies, the greatest individual level of danger for well being was constantly observed in nurses, not only as regards the traditional risks of exposure to physical or biological agents, but also the psychophysical aspecific discomfort related, particularly, both to imposition and to uncertainty in the coordination and control of technical actions and in the coordination and control of individuals. The use of an instrument of organizational analysis and the contribution of specific disciplinary approaches (the theory on stress by H. Selye and the theory on communication by G. Bateson), satisfied the needs of suggesting and understanding the relationships between organization choices and well-being of nurses, with the aim of reducing the conditions of danger for well being related to organization choices. PMID- 7791661 TI - Neurobehavioral functions in operating theatre personnel exposed to anesthetic gases. AB - Neurobehavioral functions in paramedical operating theatre personnel were assessed in a cross-sectional survey. Sixty-two subjects (40 males and 22 females) occupationally exposed to anesthetic gases were examined and compared to 46 unexposed hospital workers (18 males and 28 females). The Simple Reaction Time (SRT) test was selected from the MANS battery (Milan Automated Neurobehavioural System). In order to evaluate acute and subacute types of effects on performance, the test was administered before and after the work shift, at the beginning and at the end of the working week. In addition, the complete battery was administered during one working day without exposure to anesthetic gases. On the last day of the working week, atmospheric nitrous oxide (N2Oa) ranged from 7 to 553 ppm (geometric mean 62.6), atmospheric ethrane (ETHa) ranged from 0.1 to 18.8 ppm (geometric mean 1.3), and urinary N2O (N2Ou) ranged from 4 to 297 micrograms/l (geometric mean 26.8). An impairment of performance on the SRT test was observed at the end of the working week in subjects exposed to anesthetic gases compared to controls. This alteration was observed also considering only the subjects exposed to less than 55 micrograms/l (which is the Italian exposure limit for N2Ou, equivalent to 100 ppm for N2Oa). No significant differences were observed for the other psychometric tests. No dose-effect relationships where found between SRT test score and the indicators of exposure (N2Oa, ETHa, N2Ou).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791663 TI - [Percutaneous absorption of phenanthrene: an in vitro study of the monkey skin]. AB - It is well known that polycyclic aromatic hydrocarbons (PAHs) are absorbed through the skin of experimental animals and humans. However dermal uptake of PAHs is difficult to assess due to the lack of specific studies. The aim of this study was to obtain in vitro percutaneous absorption data for phenanthrene. In vitro penetration was measured with excised monkey (Cercopithecus Aethiops) skin in Franz diffusion cells, using a saline solution with 4% bovine serum albumin and gentamicin sulfate as receptor fluid. In two different groups of 7 and 2 cells, 38.1 and 95.3 nmol/cm2 respectively of phenanthrene were applied in an acetone vehicle. The absorption rate in the first group of 7 cells was 0.025 nmol/cm2/h (S.D. = 0.012), the lag time 11.7 (S.D. = 7.0) h and the breakthrough time 70 m (S.D. = 55 m). In the second group of 2 cells, the average absorption rate was 0.066 nmol/cm2/h and the average lag time 11.8 h. The percutaneous absorption at 24, 48 and 72 hours in the 7 cell group was 0.72% (S.D. = 0.52), 2.51% (S.D. = 1.76) and 3.9% (S.D. = 2.0) of the applied dose respectively. In the 2-cell group 1.1%, 2.78% and 4.5% of the applied dose was absorbed at 24, 48 and 72 hours. The results of the present study confirm the extent of percutaneous absorption of phenanthrene. The data can be compared with dermal absorption values of other PAHs obtained under the same experimental conditions. PMID- 7791665 TI - [Analysis of correlated data: problems and examples in industrial medicine]. AB - In occupational health we are frequently faced with data that are not independent, but to recognize the lack of such an independence is not yet a common practice. To help researchers in the field to treat correlated data in a proper way this paper has two aims: to highlight practical situations in which the data are not independent and to show the main differences between a statistical analysis which does consider the correlation appropriately and one which doesn't. As to the first aim, four typical examples are discussed: repeated measurements in the same subject (e.g., cells in which the number of sister chromatid exchanges is counted); health effects observed in multiple organs (e.g., visual impairment in both eyes); evaluation of prevention programs (e.g., exposure assessment to styrene before and after environment remediation); longitudinal studies of health effects (e.g., changes over time of pulmonary function parameters). With respect to the second aim a practical exercise is described completely. Measurements of exposure to a toxic substance in two different departments before and after environment remediation are evaluated with statistical tools which both do and do not consider the correlation between such measurements. Differences in the results obtained, with particular reference to indices of variability (e.g., standard errors), point toward the need of analysing correlated data with appropriate statistical tools that take correlation into account. PMID- 7791666 TI - [Carcinogenic agents and DL 626]. PMID- 7791667 TI - [Academic medicine versus alternative medicine]. PMID- 7791664 TI - [Determination of low levels of urinary trans,trans-muconic acid]. AB - A method is described which allows determination of urinary t,t-muconic acid (MA) by means of HPLC with UV detection even at micrograms/l concentrations. The clean up procedure of samples involves the use of strong anionic-exchange cartridges (SAX) for solid phase extraction (SPE). In order to improve the reproducibility of the retention time of MA (CV < 1%) and to obtain an adequate separation of MA from interferents, a high performance reverse-phase column (250 x 4.6 [I.D.] mm, 3 microns) is used and a careful control of the temperature (25 degrees C) is made. Also, a column-switching technique is applied to the chromatographic system in order to eliminate the highly retained peaks from the analytical column. The isocratic run is performed at a constant flow rate of 0.7 ml/min; the mobile phase consists of water: methanol: acetic acid (93.5:5.5: 1, v/v) and the UV detector is set at 259 nm. Under these conditions, MA elutes at 21.5 min and a single analysis takes 25 min; the detection limit (at a signal-to-noise ratio of 3) is 3 micrograms/l in urine, when a 200 microliters aliquot of the extract is injected in the analytical apparatus. The recovery of the clean-up procedure is > 90%; both the intra-assay and the inter-assay coefficients of variation are < 4%. The method has been applied to smokers and nonsmokers, subjects occupationally unexposed to benzene; the results showed a statistically significant difference between the two groups. Also, a close correlation was found between urinary excretion of MA measured with this method and environmental concentration of benzene in a population of workers occupationally exposed to low levels of this solvent. PMID- 7791669 TI - [Whooping cough. Microbiology, epidemiology, prevention]. PMID- 7791668 TI - [Adenosine as an anti-arrhythmia agent]. PMID- 7791670 TI - [Knowledge without information and information without knowledge]. PMID- 7791672 TI - Organ donation for transplantation. PMID- 7791673 TI - [The morphologic characteristics of the vascular network of the middle and inferior temporal gyri and middle temporal visual area]. AB - The vascular network of the anterior part of the middle and inferior temporal gyri consists of four vascular layers of which the third and fourth have the densest capillary network of the same density. There are all types of arteries in this cortex form A1 to A6 as well as all types of veins from V1 to V5. Fountain like arteries usually branch into five to six terminal recurrent branches; we have found that there are about two of them in each serial section. The middle temporal visual area has the same features of the vascular network as the above mentioned gyri with one difference only: there are at least six fountain-like arteries in each serial section. The increased number of these arteries might point to a greater sensitivity of this area to hypoxic conditions. The tangential sections of these areas reveal the existence of vertically-oriented vascular units with a centrally located venous vessel surrounded by arterial rings. PMID- 7791671 TI - Tramadol--a new oral analgesic. PMID- 7791675 TI - [Zoonoses in Vojvodina. III. Results of a seroepidemiologic study of leptospirosis in Vojvodina]. AB - 2697 persons professionally exposed to leptospira working in contaminated waters and grounds or due to contact with infected animals or their products were seroepidemiologically examined. It was established that the presence of leptospirosis in certain categories of examined persons is three to more than ten times higher in relation with it's presence in the control groups. The most frequent serotype was Leptospira pomona. None of the seropositive persons gave data about having leptospirous infection which might be the consequence of asymptomatic infection or unidentified and not registering of the clinically manifested diseases. PMID- 7791674 TI - [Prognosis in patients with myelodysplastic syndromes based on cytomorphologic and clinico-biologic parameters]. AB - Under myelodysplastic syndromes we presume a heterogeneous group of malignant hemopathies with clearly described characteristics of the disease given by a cooperative group of French, American and British authors. Myelodysplastic syndromes most frequently occur at older age. Survival of these patients, after the diagnosis is made, is mostly short because the disease evolves into acute leukemia. Myelodysplastic syndrome is characterized by appearance of refractive anemia, leukemia, thrombocytopenia with signs of expressed dishematopoiesis of the bone marrow. Clear criteria which could define forms with fast or slow course leading to acute leukemia don't exist, so there is a need to group patients into those with good or with bad outcome. The investigation included following parameters important for the outlook of the disease: 1. enlargement of lymph nodes, liver and spleen, 2. biochemical examination of peripheral blood, 3. cytomorphologic changes in the peripheral blood cells and bone marrow. By a follow-up of described parameters a statistically significant influence on survival of the sick concerning the degree of present anemia, absolute number of granulocytes, number of thrombocytes, dishematopoiesis of the peripheral blood and bone marrow, lymphadenomegaly, hepatomegaly and splenomegaly was not found. The percentage of blast in the peripheral blood and bone marrow has a statistically significant influence on patients' short survival. PMID- 7791677 TI - [Use of antibiotics in ambulatory pediatric care during the economic blockade]. AB - Antibiotics are the most frequently prescribed drugs in the pediatric out-patient practice. The author, on the base of his personal experience, identifies and discusses relevant factors for the proper usage of antibiotics, through their behaviour under the conditions of economic blockade. These factors are: pharmaceutical industry, physician, patient and pharmacist. The shortage of many antibiotics as well as reduced communications of pharmaceutical companies with physicians, significantly disturb the therapeutical decision making process. Because of that, a physician has to confront optimal therapy, present situation in pharmacies, but also the economical power of patients--the availability of most antibiotics is possible only in the private sector. Wrong attitudes and habits of patients and of some physician with superficial approach to antibiotics irresponsible exchanges of antibiotics by some pharmacists and issuing antibiotics without prescription in the private sector, potentiate possibilities for misuse. Interaction of the mentioned factors determines present and future validity of antibiotics. The paper warns about the climate of their uncontrolled ways and suggests measurements for possible correction of present situation. PMID- 7791678 TI - [Backache in children]. AB - Back ache is a rare phenomenon in children and adolescents, but it is always caused by serious pathologic changes. The aim of this study was to point to pediatricians to the importance of anamnesis and clinical examinations in making a diagnosis. PMID- 7791679 TI - [Correlation of histomorphologic changes in the blood vessels of diabetic patients in the aging processes]. AB - The increase of morbidity concerning diseases of heart, CNS, kidneys and of other organs is primarily connected with atherosclerotic changes of blood vessels. The population of cardiovascular patients includes a great number of diabetics and in that case manifestations of illness are directly conditioned and connected with changes of blood vessels. PMID- 7791682 TI - [Echocardiographic evaluation of the effect of treatment with captopril in patients with essential hypertension]. AB - Numerous antihypertensive drugs act through different mechanisms so it is natural to expect their various effects on consecutive myocardial changes. This study included 40 patients with mild or moderate hypertension: 30 patients (19 male- 63.3% and 11 female--36.7%), their mean age 40.1 year, who were treated with Kaptopril (Zorkaptil), and 10 patients (6 female--60% and 4 male--40%), their mean age 37.7 years, who received placebo. Before the beginning of the treatment and three months later the following data were analyzed: blood pressure, the left ventricular mass, the left ventricular mass index, shortening fraction, ejection fraction and the endsystolic left wall stress. Three months later in the group treated with Kaptopril significant reduction of blood pressure, left ventricular mass, left ventricular mass index and endsystolic left wall stress (p < 0.05) was found. The changes concerning ejection fraction and shortening fraction were not significant. Three months later, in the group which received placebo no changes could be found. It can be concluded that Kaptopril is an effective antihypertensive drug for treating some cases of mild and moderate hypertension as monotherapy not only because it control the blood pressure, but also because it significantly reduces the wall thickness of the left ventricular mass and of the endsystolic left wall stress. PMID- 7791680 TI - [Chronic atrophic gastritis as a precursor to gastric carcinoma]. AB - According to clinical and histological researches, a conclusion can be accepted that the chronic atrophic gastritis is a very serious precancerous condition of stomach. Biological key and connection between these two entities seemed to be intestinal metaplasia, but it has been suggested lately, that the dysplasia of gastric mucose was responsible for malignant proliferation in stomach mucose. The aim of this study was to determine the precancerous potential of the chronic atrophic gastritis, measuring the frequency of dysplasia of gastric mucose, type II and III, which are considered as precancerous lesions. The results (according to t-test) in the tested group (61 patient with histologically proved chronic atrophic gastritis) comparing to the control group (64 healthy persons), showed statistically highly significant difference in appearance of dysplasia of gastric mucose type II and III. It confirms high precancerous potential of the chronic atrophic gastritis and the need for frequent endoscopic and histologic examinations of these patients. PMID- 7791676 TI - [Treatment of retinal detachment with a giant rupture]. AB - Results of surgical treatment in 29 cases of retinal detachment caused by giant tear have been reviewed. Two patients have been operated on by scleral buckling procedure, whereas in 27 cases vitreoretinal surgery in combination with silicone oil tamponade has been performed. Anatomic success was achieved in 20 of 29 eyes. After a follow-up period of 6 to 36 months 20 eyes (69%) had visual acuity equal to or better than 0.3. Silicone oil has been successfully evacuated out of 14 eyes with retina remaining attached. PMID- 7791681 TI - [Types of atherosclerotic changes in relation to the type of residual lumen and degree of narrowing in coronary arteries in ischemic heart disease]. AB - 510 segments of all three coronary arteries in 50 obduction cases of individuals suffering from ischemic (coronary) heart disease were microscopically examined. We examined the type of atherosclerotic change, the degree of narrowness of lumen artery and the type of residual lumen. In the group one of the narrowness of artery lumen 44 segments with fibrotic plaque were found, where concentric shape of lumen dominates. In the group two of the narrowness 176 segments were found. Most of them were with fibrotic plaque, but complicated atherosclerotic lesions were also present. According to the shape of residual lumen the concentric narrow shape dominates. In the group three of the narrowness of the lumen 191 segments were found; considering the type of atherosclerotic change complicated lesions were most common, while lipidic plaque was also present. An eccentric shape of residual lumen dominates this group. In the group four of the narrowness of lumen artery 99 segments were found; in this group we found fibrotic plaque and complicated atherosclerotic lesions. The most common finding of the residual lumen is the type of multiple lumen (channelled thrombi). PMID- 7791685 TI - [Surgical and prosthetic reconstruction of post-tumor defects of the face (case report)]. AB - This paper shows a combination of methods in treatment of a facial post tumorous defect. Simultaneous surgical and prosthetic reconstruction was used when treating ablation of the facial basal cell carcinoma in a 70 year old female patient. When planning this surgery the next must be taken into consideration: the age of the patient, general health condition and the size and type of the defect, especially of the bone structures. It means that collaboration between the surgeon and prosthetic is of great importance. In this way a very fast facial rejuvenation can be achieved, even in large defects which enables not only healing but further social rehabilitation of such patients too. PMID- 7791684 TI - [Analysis of causes and sequelae of highway accidents in the region of Nis]. AB - During the last five years there were 12,556 traffic accidents; there were injured persons in 2753 accidents which makes 21.9% (225 killed, 598 seriously and 210 lightly injured). Among the killed victims motor vehicle drivers are dominant, among the seriously injured are pedestrians and travellers are dominant in the group of lightly injured. In these accidents 404 children were injured, mostly 8-11 years of age. In most cases causes of death are polytrauma and craniocerebral injuries. The most frequent causes of traffic accidents resulting injured persons are: traffic regulations not being respected, bad psychophysical state of drivers and vehicle technical defects. The first two reasons are causes of serious traffic accidents. It has been established that weather conditions influence the occurrence and seriousness of traffic accidents, so that this area is characterized by a maximal number of accidents and injured persons during the period May--August. PMID- 7791686 TI - [Case report of a patient with Pott's disease]. AB - The author presents a case of tuberculosis inflammation of thoracic vertebra with cold abcess along the spinal column, Pott's disease, in a woman 42 years old, a worker, with subjective difficulties which had lasted over a year before the diagnosis was made. TBC lungs and other localities was in regression in the last 30 year, it was even thought overhauled. But in recent times because of great migrations of the population and the fall of personal and social standards growth of new cases as well as revival of the old ones has been observed. Hard cases of lung tuberculosis in the first place and then of other localities have been diagnosed sporadically since fluorography has not been done for a longer time due to wellknown reasons. The reasons for making diagnoses in the terminal phase of the shown case are the instilled manner and opinion of the physicians belonging to previous peaceful times that tuberculosis has been overhauled, so that now many of them react inertly about this disease. The author wants this review to be seen inside the actual conditions of life, work, nutrition, hygiene, health care possibilities and health care. PMID- 7791683 TI - [Mortality in laryngeal cancer in Belgrade 1982-1991]. AB - The paper reviews data on mortality caused by larynx cancer in Belgrade from 1982 to 1991. The gathered results indicate that larynx cancer was the cause of death in 2.01% on average of all deceased of all kinds of malignant tumors (3.17%, male 0.67% female), while it makes 8.18% of the deceased of malignant tumors of the respiratory tract (9.5% male, 5.21% female). The standardized mortality rates during the 10 year period occurred in 1.84 to 3.05 cases per 100,000 inhabitants (2.60%/100000 average). In males the rates were from 3.65 to 6.01%/100000 (4.91%/100000 average) and in females from 0.32 to 1.13%/100000 (0.69%/100000 average). The specific mortality rates according to age were extremely low up to the age of 44, then an abrupt increase happens, while the occurrence of the highest values is present in the oldest group. The mortality trend concerning larynx cancer during the ten year period points to the fact that there is a slight decrease as well in males (y = 5.02-0.02x) as in females (y = 1.06-0.07x). PMID- 7791687 TI - [Dr. Ante Sokcic on the 55th anniversary of the founding of the otorhinolaryngology department in Subotica]. PMID- 7791689 TI - Time-frequency spectral analysis of electric field plethysmography signals. AB - Cardiac activity contaminates respiratory electric field plethysmography (EFPG) signals, and vice versa, and is usually treated as an artefact. On the other hand, simultaneous information on respiration and cardiac activity is often required in clinical practice. Hence, we use time-frequency spectral analysis (TFSA) by means of the spectrogram (SG) to investigate the instantaneous cardio respiratory information contained in EFPG-signals and show that it is a practical means of extracting this information out of a single EFPG-signal. Comparisons with a Wigner distribution reveal sufficient time-frequency resolution of the SG for detection of physiological events in EFPG-signals. SG-analysis indicates spectral peaks related to respiration and cardiac activity (depending on the electrode configuration, up to the third and fifth harmonic, respectively) and the possibility to detect respiratory sinus arrhythmia by means of EFPG measurements. Intermodulation products cause overlaps of respiratory and cardiac spectra pointing out nonlinear relationships. Additionally, SG-analysis supplies essential information for the separation of EFPG-signals into respiratory and cardiac components, by means of filter techniques. PMID- 7791690 TI - Electrical impedance for estimation of irritation in oral mucosa and skin. AB - Our aim is to establish an objective, easy-to-use technique to evaluate tissue irritation in vivo using non-invasive electrical impedance measurements. Such a technique would facilitate testing the biocompatibility of various materials, and also in quantifying skin diseases and other processes involving structural changes. It has been found that irritation of the oral mucosa not clinically or histologically discernible could be detected with a simple device based on electrical impedance techniques. Originally, the key problem was to focus the probing electrical field in order to minimize artefacts emanating from tissue layers of no interest. The device was then refined and applied to skin testing. It was found that irritation effects far below the limit of the commonly used visual readings could be detected. In this case, it is desirable to exclude from the measurement tissue layers with no diagnostic information, or at least reduce their influence. In this paper, the essential steps of the development of a multi frequency depth selective device are reviewed. PMID- 7791691 TI - Color quantification in angioscopic video images. AB - Colors in video representations of angioscopic images are up until now described by an human observer. Differences in settings of the monitor and the inherent poor ability of the human eye to classify colors objectively results in a very poor intraobserver as well as interobserver variability. A PC-based method is described to measure colors in a video image and to present the results in a novel C-diagram. Results with this method for standard calibrated colors are given. Possible sources of error are discussed and methods to minimize these errors are presented. PMID- 7791688 TI - New aspects in electrostimulation of the heart. AB - The interaction of the autonomic nervous system (ANS) and the heart is characterized by a new interdisciplinary field known as neurocardiology which presents the newest strategy for electro-cardiostimulation. In this context, the reestablishment of chronotropy with physiological, closed-loop pacing, as well as the prevention and treatment of a malignant arrhythmia by ANS modulation, is of the highest priority. The main objective toward this goal consists of appropriate monitoring of the autonomic balance and stimulation, respectively, so that neuromodulation of the cardiac efferents can be established. The electrode, as a sensor and an actuator, with its interface on the cellular level becomes of essential importance. The electrode-myocardium interface is determined by the structure of the Helmholtz double layer with regard to its physical, electrochemical, and physiological behavior. The transportation of electrons across the boundary, as well as the electro-chemical reactions determining the biocompatibility of the interface, can be improved by the microstructure of the solid component by creating a fractal surface coating with titanium-nitride or iridium. Experimental and clinical results have demonstrated that the fractal structure ensures negligible polarization as well as improved detection performance, thus, detecting the evoked response of the myocardial cells makes it possible to monitor the neural response of the myocardium as a consequence of a superimposed chronotropic disturbance. The stimulation electrode also monitors the sympathetic activity extracted from intracardiac impedance measurements, thereby providing a new principle of rate adaptation in which the pacemaker is an integral part of the ANS, reestablishing normal chronotropy. Further advantages of the improved electrode interface performance open new aspects in the treatment and prevention of tachyarrhythmia, and in the follow-up of transplanted hearts for the prevention of the rejection processes. PMID- 7791693 TI - [Opening address by the chairman of the 101st Congress of the German Society of Internal Medicine, Wiesbaden, 23 April 1995. The future]. PMID- 7791692 TI - The cochlear implant. A technology for the profoundly deaf. AB - The cochlear implant is a device that enables the profoundly deaf to hear. This article considers the nature of the technology, the need for rehabilitation programs for those who are implanted and the evidence of benefits from this approach. A preliminary economic assessment suggests that costs per QALY for this technology would be of the order of $ 14,000 for children and $ 22,000 for adults. Cochlear implantation appears to be superior to vibrotactile devices, and is an effective technology for appropriately selected persons. PMID- 7791694 TI - [Factitious disease caused by secret administration of the oral anticoagulant phenprocoumon: study of 16 personal cases]. AB - BACKGROUND: It is frequently difficult to disclose covert ingestion of cumarins being the underlying cause of a bleeding disorder. PATIENTS AND METHODS: We report on 16 cases (15 patients) of phenprocoumon (Marcumar) abuse. All patients (9 females, 6 males) were admitted to the hospital because of bleeding and/or prolonged thromboplastin times. Analysis of phenprocoumon in the blood was performed by HPLC. RESULTS AND CONCLUSIONS: The clinical presentation of the bleeding was highly variable. Thromboplastin times ranged from < 5 to 58%. With the exception of two patients with hepatic dysfunctions factor V activity was normal. All but one patient denied the ingestion of Marcumar. One patient died from hemorrhage. Two types of patients emerge from our series: Type I is the young nurse (8 cases), type II the usually male patient formerly treated with phenprocoumon (5 cases). Type I patients had long medical histories and showed autoaggressive behavior including the artificial manipulation of disorders other than hemorrhage. Thromboplastin times however were within or close to the therapeutic range (10 to 25%). Type II patients did not simulate other diseases in addition to hemorrhage. Thromboplastin times were longer than in type I patients. In all instances discrimination between non suicidal and suicidal behaviour was difficult. Psychiatric consultance is indicated. PMID- 7791695 TI - [Diagnosis and therapy of Gaucher disease]. AB - BACKGROUND: Since 3 years there is an effective enzyme replacement therapy for patients with Gaucher's disease which is the most prevalent sphingolipid storage disease. Also the diagnostic procedures have recently been improved. This study reports about the results of longterm enzyme replacement therapy and the diagnostic workup in 18 patients with Gaucher's disease. PATIENTS AND METHODS: Since June 1991, 18 patients with moderate to severe degree of Gaucher's disease were treated by administration of modified human glucocerebrosidase on regular bases in the University Hospital Dusseldorf. According to the severity of the disease, glucocerebrosidase infusion was performed every 2 weeks. The dosage was individually chosen according to the severity of the disease. RESULTS: Within 3 to 4 months all patients showed an improvement of laboratory findings, of hepatosplenomegaly and of their general well-being. CONCLUSIONS: The advances in our understanding of this disease need to be publicized because an early diagnosis and timely enzyme replacement guarantees almost all patients with the adult type of Gaucher's disease to live a normal life without complaints and complications. PMID- 7791696 TI - [Patient with acute dyspnea and thoracic pain after sclerotherapy of esophageal varices]. PMID- 7791697 TI - [Rheumatology update--II. Overview of the clinically important status of knowledge and prospects for possible relevant trends in etiopathogenetic research, diagnostic methods and therapeutic possibilities]. PMID- 7791698 TI - [Drug therapy of acute hemorrhage from esophageal varices]. PMID- 7791699 TI - [Factitious disease]. PMID- 7791700 TI - [Delayed manifestation of post-hypoxic leukoencephalopathy]. PMID- 7791701 TI - [Parotid swelling after DNCG aerosol]. PMID- 7791702 TI - [Infantile seborrheic dermatitis]. PMID- 7791703 TI - [Anemia of prematurity: risk factors influencing red cell transfusions]. AB - To investigate the importance of transfusion practice with packed red cells (PRCs) in premature infants and to identify risk factors significant influencing transfusion practice, we analyzed 75 preterm infants (gestational age: 31 +/- 2 weeks; birth weight: 1459 +/- 402 g) admitted to the neonatal intensive care unit of Catholic University of Rome. Fifty-three (70.7%) of the infants received one or more PRCs transfusions (in total 246 transfusions). The variables associated with an increase in number and frequency of PRCs transfusions were: a) gestational age < or = 30 weeks; b) birth weight < or = 1000 g; c) severe neonatal pathology (ie a respiratory disease requiring ventilatory support and/or a clearly documented or suspected sepsis). Repeated PRCs transfusions during the first week of life significantly (p < 0.01) influenced the need for late transfusions, after 4 weeks of age, for the treatment of the anemia of prematurity. These data indicate that preterm infants with a gestational age < or = 30 weeks, a birth weight < 1000 g and a severe respiratory or infectious disease represent natural candidates for administration of recombinant human erythropoietin to reduce the need for late PRCs transfusions. PMID- 7791705 TI - [Alpha-1 antitrypsin deficiency. A diagnostic approach and case report]. AB - Subjects with alpha 1-antitrypsin deficiency, Pizz, are often subject to hepatopathies in infancy and pneumopathies in adulthood. The authors make a number of genetic and clinical observations together with a laboratory diagnosis of alpha 1-antitrypsin and describe an asymptomatic clinical case in which the diagnosis of alpha 1-antitrypsin in a PiZZ phenotype was made following the initial and occasional finding of altered transaminase and alpha 1-globulin values. PMID- 7791704 TI - [Celiac disease and cystic fibrosis: casual association?]. AB - The authors describe a case of association cystic fibrosis coeliac disease, which they have observed. The frequency of this association in the general population is of 1:2,000,000. M.A. presents little growth in terms of height and weight and intestinal alterations (an abundance of fatty and mucous stool). The initial diagnosis was that of coeliac disease. After two months of diet without gluten one observed an increase in weight, but o result for the intestinal disturbances. The positive result revealed from the sweat-test and the study of genomic mutation (delta F508) showed the diagnosis of cystic fibrosis associated with coeliac disease. The specific treatment of both syndromes resolved intestinal alterations and caused the diminution of the acute bronchitis frequent during the first and the second infancy. PMID- 7791708 TI - [Williams-Beuren syndrome and celiac disease]. AB - The authors describe a case of Williams syndrome-Coeliac Disease that they have observed at the age of three years and 10/12. There are few reports in the literature. We focus on the variability of clinical and biochemical aspects of Williams Disease and the necessity for an adequate gastroenterologic follow-up (anti-gliadine antibody and anti-endomisium antibody) in these patients with little growth in terms of weight and height and intestinal alterations present in superior measure in companion with the reported standards for the same syndrome. PMID- 7791709 TI - [Is it possible to speak about theoretical pediatrics?]. PMID- 7791707 TI - [The clinical syndrome associated with antiphospholipid antibodies. A diagnosis to be confirmed after a long follow-up]. AB - A clinical case of syndrome of antiphospholipid antibodies is reported. The patient is a 10-year-old girl with thrombophlebitis of the right leg associated with the presence of lupus-like anticoagulant antibodies. No secondary pathologies were found. It is not possible, anyway, to make a definitive differential diagnosis between primary and secondary forms of syndrome of antiphospholipid antibodies because of intermediate situations where antiphospholipid antibodies are associated with 2 or 3 ARA criteria for the diagnosis of lupus (lupus-like syndrome). A long term follow-up is therefore necessary. PMID- 7791706 TI - [Clinical and pathogenetic observation in a case of pulmonary hemosiderosis]. AB - Pulmonary hemosiderosis is a rare disease of unknown aetiology, whose clinical, pathogenetic and prognostic aspects are still open to discussion. The authors report a case of pulmonary hemosiderosis in a 2 years and 3 months old girl. Peculiar features of this case include antibody deficiency (which may contribute to the pathogenesis of the disease) and severe and protracted melena. Fatal outcome, despite several therapeutic trials, confirms the poor prognosis of pulmonary hemosiderosis. PMID- 7791710 TI - [Nutritional prevention of allergies]. PMID- 7791711 TI - [Follow-up study of pulmonary function in individuals subjected to lobectomy in infancy and childhood]. AB - Experimental research in animals have demonstrated that pulmonary development continues after birth. This happens in man as well: alveolar proliferation and enlargement go on until the eighth year of age, furthermore complete pulmonary development is achieved until the 20-22 years of age. It is therefore possible to hypothesise that respiratory deficit following pulmonary exeresis in children would regress with time. In the Pediatric Surgery of IRCCS Policlinico S. Matteo of Pavia eight children, 4 days to 8 years of age, underwent lobectomy for pulmonary hypertensive emphysema (3), lung abscess (2), bronchogenic cysts (2) and hystiocytoma (1). One of them was lost to follow-up; the remainders were controlled from 3 to 25 years after surgery: all of them enjoy a normal active life. Respiratory function was evaluated through blood chemistry, blood gas analysis, basal and after strain ECG, chest X-ray, spirometry, basal and after strain pulmonary scintigraphy. Basal and after strain ECG, chest X-ray, and arterial blood gas were normal in every examined subjects; spirometry, although results are quite variable, did not show serious respiratory deficits; basal after strain pulmonary scintigraphies weren't homogeneous. These results, although they aren't univocally interpretable, positively confirmed that the residual lung after lobectomy has a satisfactory possibility of functional recovery. PMID- 7791712 TI - [Laparoscopic surgery in pediatric age]. PMID- 7791713 TI - [Beta-cell secretion in patients with thalassemia major]. AB - Diabetes mellitus is one of the main endocrinological disease complicating the course of thalassemia major. This study aimed evaluate beta-cell secretion in 24 patients with thalassemia major attending the hematological Day Hospital at the Pediatric Clinic in Modena where transfusion therapy is performed in all thalassemic patients so as to maintain minimum hemoglobin levels above 10.5 g/dl, together with intensive ferrochelating therapy (desferrioxamine 50-60 mg/kg/die s.c. 6 days a week). A C peptide challenge with glucagon was performed in three patients already receiving insulin therapy for diabetes mellitus; this unexpectedly revealed a slight residual beta-cell secretion. An intravenous glucose tolerance test (IVGTT) was performed in the remaining 21 non-diabetic patients, with widely varying findings regarding insulin secretion: from below 50 microUl/ml in 5 patients to above 200 microUl/ml in 5 patients, and between 50 and 150 microUl/ml in the remaining 11 patients. This study therefore confirmed that insulin secretion frequently alters in thalassemic patients. Moreover, insulin secretion is not correlated to ferritinemia or influenced by familiar diabetes or patient age. PMID- 7791715 TI - [Description of two cases of Munchausen syndrome by proxy]. AB - The Munchausen syndrome by proxy, or Polle syndrome can be considered as a form of child abuse in which parents falsify or even produce a real pathology in their children submitting them to frequent hospitalizations and pointless medical examinations. The authors discuss two cases and emphasize the importance of an early identification of these cases to avoid psychical impairments that inevitably stem from this "new" form of child abuse. PMID- 7791714 TI - [Primary response to tetanus toxoid stimulation in early infancy]. AB - The authors attempt to evaluate the degree of immune response to the first dose of anti-tetanus vaccination in young infants and to study the correlation between maternal and infantile antitetanus antibody titers. The sample studied comprised 5 males and 5 females aged between 61 and 75 days old, without acute and/or chronic pathologies and uncircumsized. Three samples of peripheral venous blood were collected for each infant: 1 at time 0, and the other two during the 15 days after the administration of the first dose of tetanus toxoid. The results support the hypothesis that vaccinal stimulation has a greater effect on cellular rather than humoral immunity, causing an increase in the CD4/CD8 ratio and a decrease in CD16. The study confirms that women with high antitetanus antibody titers during pregnancy have children with protective antibody titers. This underlines the importance of vaccinating pregnant women who, for various reasons, have not been immunised so as to prevent infantile tetanus and to allow the possibility of delaying, if necessary, the administration of the first dose of toxoid in infants without the risk of short-term toxoinfection. PMID- 7791716 TI - [Wolfram syndrome. Peculiar urologic aspects]. AB - The 6-year follow-up of a patient affected by Wolfram's syndrome, a rare disease characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), neurosensory deafness (D), atony of the urinary tract and other abnormalities (DIDMOAD or Wolfram's syndrome), is described. Our patient has diabetes insipidus, diabetes mellitus, abnormal audiograms, without subjective evidence of hearing loss, and dilatation of the urinary tract. Diagnosis was suspected at the age of 8 years. Diabetes mellitus was the first manifestation and treatment with insulin was necessary. Desmopressin therapy decreased dramatically the daily urinary output. In view of the significant morbidity and mortality from renal failure associated with recurrent urinary infections, we have drawn special attention to the urological manifestations of the syndrome. During the follow-up, the patients underwent some investigations, such as renal ultrasound and echotomography and cystourethroscopy. Outstanding results of these studies are severe bilateral hydronephrosis with dilatated ureters and loss of renal tissue. The particular finding is the presence of posterior urethral valves with obstructed bladder. The anatomical outlet obstruction are variable and may be disastrous. There may be failure to thrive, sepsis, anemia be disanal failure. In such instances corrective surgery could improve bladder and ureteral functions. PMID- 7791717 TI - [Cohen syndrome. A new case and review of the literature]. AB - We report the case of a 12-year-old child suffering from mild mental retardation, hypotonia, long hands with tapering fingers, microcephaly, truncal obesity, particular facial features. The association of these abnormalities has been known as Cohen Syndrome since 1973. Such a dysmorphic syndrome is usually inherited as an autosomal recessive trait whose gene has not been yet localized. There is no biological marker and the diagnosis is made only on a clinical basis. The diagnosis is quite difficult because of the intrafamiliar variation and the lack of a symptom present in 100% of the cases. From the analysis of the literature it proves that the more frequent symptoms are: mental retardation, open mouth, short philtrum, high palate, hypotonia. Because of the diagnostic difficulties it is possible that this syndrome was underestimate. Moreover, it is usually diagnosed too late, (mean age: 12,9). Therefore, we think necessary to consider the possibility of Cohen Syndrome in the case of every mental retardation of unknown cause. PMID- 7791718 TI - [Seckel syndrome. Report of a case]. AB - The paper report a case of Seckel's syndrome in a girl aged 7 years and 2 months who was referred to the authors attention due to abdominal colic. Low birth weight together with a significant delay in weight and stature increase, microcephalia with the typical bird head and considerable mental retardation were sufficient to diagnose the syndrome. Interesting analogies were observed with another case of a patient with Seckel's syndrome born to an epileptic mother receiving antiepileptic treatment which was suspended during the second month of gestation. In the case presented here, no drugs were taken during pregnancy although the mother had received antiepilepsy treatment for years. PMID- 7791719 TI - [Description of two cases of transient hyperphosphatasemia in infancy and childhood]. AB - The authors describe two cases of benign transient hyperphosphatesamia of infancy. This form is not so frequent in childhood and the following criteria must be present for a correct diagnosis: 1) Patient age of less than 5 years. 2) Variable symptoms. 3) No bone or liver disease noted on physical examination. 4) No other biochemical or laboratory evidence for bone or liver disease. 5) A return to normal serum alkaline phosphatase levels within 4 months with no sequelae. We want underline the uselessness of vitamin D therapy and the importance of a deepened study about biochemical and laboratory parameters in all patients affected by alkaline hyperphosphatesamia, to exclude a possible severe disease. PMID- 7791720 TI - [Jejunal biopsy with Watson's capsule and erythromycin]. PMID- 7791721 TI - Doling out risk. How capitation measures up in Minnesota. PMID- 7791722 TI - Is capitation right for your practice? PMID- 7791723 TI - Enough to raise one's blood pressure. PMID- 7791724 TI - Who bears the risk when physicians are also insurers? PMID- 7791726 TI - MinnesotaCare bills move forward. PMID- 7791725 TI - Celiac sprue in an asymptomatic elderly man. AB - The authors discuss the case of an asymptomatic patient with celiac sprue presenting with hematologic abnormalities on screening laboratory examination. The patient was initially treated for vitamin B-12 and folate deficiency, and subsequently for iron deficiency with limited success until the diagnosis was established. The absence of such classic features of celiac disease as steatorrhea and diarrhea is not an uncommon presentation. Unexplained iron deficiency should alert the clinician to the possibility of celiac sprue. PMID- 7791727 TI - Direct contracting can put doctors in the driver's seat. PMID- 7791728 TI - MMA strongly opposes Vulnerable Adults Act. PMID- 7791730 TI - Capitation without trepidation. PMID- 7791729 TI - Higher office to higher learning. PMID- 7791731 TI - Physician leadership: developing a physician-directed, community-based managed care network. PMID- 7791732 TI - Managed care plus (MC+): the wave of the future for Missouri Medicaid? PMID- 7791733 TI - Otolaryngology quiz #4. Metastatic carcinoma. PMID- 7791734 TI - Efficacy of thymectomy in myasthenia gravis. AB - We sought to determine the efficacy of thymectomy in patients with myasthenia gravis (MG). The roles of age, gender, age of onset of MG, acetylcholine receptor antibodies (AchR's) titers, and pathology of the thymus gland were evaluated. Twenty-one patients were analyzed retrospectively. Twenty patients belonged to Osserman Class IIA or higher; 71.42% belonged to IIB. All patients were on either anticholinesterase and/or immunosuppressive agents. The mean follow up was three years. Seventy-six percent of the patients showed improvement by Osserman and by "results of treatment" classification, 14.28% were in complete remission, on no medications. The age, gender, age of onset, thymic pathology and AchR titers had no correlation with post-operative improvement. With longer follow up the beneficial effect is more apparent. PMID- 7791735 TI - Farm-tractor-related fatalities--Kentucky, 1994. AB - Fatalities associated with farm tractors are the most common cause of work related death in the U.S. agricultural industry (1). To characterize farm-tractor related fatalities in Kentucky, the Kentucky Fatality Assessment and Control Evaluation (KY FACE) Project studied all fatal farm injuries occurring among persons in that state during 1994, the initial year of operation for FACE in Kentucky. This report summarizes the results of that study. PMID- 7791736 TI - Mass treatment of humans exposed to rabies--New Hampshire, 1994. AB - On October 22, 1994, the laboratory of the New Hampshire Division of Public Health Services (NHDPHS) diagnosed rabies in a kitten that had been purchased from a pet store in Concord, New Hampshire. On October 19, the animal had developed seizures, then died of unknown causes during the night of October 20 21. Approximately 665 persons received rabies postexposure prophylaxis because of exposure to this kitten and other cats from the same pet store. This report summarizes the epidemiologic investigation of the source of the infection and follow-up care of humans and animals potentially exposed to rabies. PMID- 7791737 TI - Measles--United States, 1994. AB - As of June 13, 1995, local and state health departments in 39 states had reported 958 measles cases to CDC for 1994. This represents the second lowest number of cases ever reported, after the historic low of 312 cases in 1993 (1). In addition, 303 cases were reported for the U.S. territory of Guam (228) and the commonwealths of the Northern Mariana Islands (29) and Puerto Rico (46). This report summarizes the epidemiologic characteristics of measles cases and outbreaks reported in the United States during 1994. PMID- 7791738 TI - Prevalence of smoking by area of residence--Missouri, 1989-1991. AB - Variation in smoking prevalence by area of residence may be an important consideration in the development, implementation, and management of programs that promote nonsmoking. In general, the prevalence of cigarette smoking is highest among persons at economic, educational, and social disadvantage (1,2), and the proportion of persons who are disadvantaged is greater in urban and nonmetropolitan areas. Because smoking prevalence varies by area of residence and characterization of these differences can assist in directing efforts to promote nonsmoking, the Missouri Department of Health compared urban, suburban, and nonmetropolitan areas using data from two sources: the Behavioral Risk Factor Surveillance System (BRFSS) for Missouri from 1989 through 1991 (suburban and nonmetropolitan areas) and a survey specially commissioned in 1990 (Smoking Cessation in Black Americans [SCBA]) of persons living in low-income census tracts in north St. Louis and central Kansas City (urban areas). This report summarizes the results of this analysis. PMID- 7791739 TI - Increase of (Ca(2+)-Mg2+)-ATPase activity in hepatic plasma membranes of rats administered orally calcium: the endogenous role of regucalcin. AB - The alteration of the plasma membrane (Ca(2+)-Mg2+)-ATPase activity in the liver of rats administered orally calcium chloride solution was investigated. The plasma membrane (Ca(2+)-Mg2+)-ATPase activity was significantly increased by a single oral administration of calcium (10, 25 and 50 mg/100 g body weight) in rats. This increase was seen between 10 and 60 min after the administration. The presence of anti-regucalcin IgG (1.0-5.0 micrograms/ml) in the enzyme reaction mixture caused a complete inhibition for the elevation of the plasma membrane (Ca(2+)-Mg2+)-ATPase activity by the addition of regucalcin (0.25 microM). Also, the calcium administration-induced increase in hepatic plasma membrane (Ca(2+) Mg2+)-ATPase activity was completely abolished by the presence of anti-regucalcin IgG (1.0 and 2.5 micrograms/ml). Moreover, the calcium administration-induced increase in hepatic plasma membrane (Ca(2+)-Mg2+)-ATPase activity was not inhibited by vanadate (0.1 and 0.2 mM) addition into the enzyme reaction mixture, although the inhibitory effect of vanadate was seen in the plasma membranes from normal rat liver. Now, the activating effect of regucalcin (0.25 microM) on hepatic plasma membrane (Ca(2+)-Mg2+)-ATPase was not inhibited by vanadate addition. The endogenous regucalcin may play a role in the calcium administration induced increase of (Ca(2+)-Mg2+)-ATPase activity in the liver plasma membranes of rats. PMID- 7791740 TI - In vivo effect of vitamin E on serum and tissue glycoprotein levels in perchloroethylene induced cytotoxicity. AB - The antioxidant efficacy of vitamin E on Perchloroethylene (PER) induced cytotoxicity has been studied in rats. Feeding PER to rats for 42 days using sesame oil as vehicle alters total protein and protein bound carbohydrate components in liver and kidney of experimental animals. Supplementation of vitamin E prevented the changes observed in total protein and protein bound carbohydrate components of PER administered rats. Histopathological studies also show the effectiveness of vitamin E on PER administered rats in protecting the cellular architecture of liver and kidney from PER induced cytotoxicity. PMID- 7791741 TI - Effect of ischemia-reperfusion injury on the morphology of peroxisomes. AB - We have previously demonstrated that ischemic injury changed the density of peroxisomes into two distinct peaks, one with a normal density (1.21 g/cm3; Peak I) and a second peak with a lighter density (1.14 g/cm3; Peak II). We studied the peroxisomes from both peaks under the Electron microscope. Examination of peak I following ischemia showed loss of matrix proteins and damaged limiting membranes with leakage of DAB positive material in direct proportion to the duration of ischemia. Upon reperfusion of the ischemic liver Peak I showed more severe damage to the organelle. These observations clearly demonstrated that ischemia reperfusion injury causes structural damage to peroxisomes. Interestingly ultrastructural examination of Peak II following ischemia showed evidence of perisomal proliferation with budding of existing peroxisomes and the presence of micro peroxisomes (changes similar to those noted under conditions leading to perisomal proliferation). However, peak II following reperfusion showed only damaged organelle. These observations underline the importance of peroxisomes in the response of the cell to ischemia-reperfusion injury. PMID- 7791742 TI - Potential involvement of a constitutive heat shock element binding factor in the regulation of chemical stress-induced hsp70 gene expression. AB - It was reported that chemical stresses such as arsenite, cadmium or salicylate fail to induce synthesis of the inducible form of HSP70 (HSP70i). We report here that exposure of cells to higher doses of these chemical treatments induced significant synthesis of HSP70i in CHO cells as well as other cell lines. The synthesis of HSP70i is primarily regulated at the transcriptional level. Although all tested chemical treatments induced heat shock factor (HSF) binding to the heat shock element (HSE), HSP70i synthesis appears to be regulated by an alternative factor (CHBF) which constitutively binds to the HSE at 37 degrees C. The treatments, which dissociate the HSE-CHBF complex, induced significant HSP70i synthesis. The treatments, which failed to induce HSP70i synthesis, still activated HSF binding to HSE but the HSE-CHBF complex remained as that of untreated control cells. PMID- 7791743 TI - Extracellular matrix components and proteolytic enzymes in uterine cervical carcinoma. AB - The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels. PMID- 7791744 TI - Expression of GTP-binding protein alpha subunits in human thymocytes. AB - In this report, we investigate G protein alpha subunit diversity in human thymocytes, utilizing common properties shared by these genes and reverse transcription-polymerase chain reaction (RT-PCR). Sequence analysis of PCR amplified gene portions, indicate the presence of members from all four G-protein families that have been described thus far. The alpha subunit genes identified are: G alpha i1-3 and G alpha z but not G alpha o from the Gi family, G alpha s from the Gs family, G alpha 11, G alpha q, and G alpha 16 from the Gq family, and G alpha 12 and G alpha 13 from the G12 family. Also in this report we present the nucleotide and predicted amino acid sequences of the human G alpha 13 cloned from a thymocyte cDNA library. The sequence of the human G alpha 13 has not been previously reported. Comparison of this sequence with the reported murine G alpha 13 shows > 90% identity at the deduced amino acid sequence level. We conclude that thymocytes represent a useful experimental system for the study of G protein involvement in immune responses and lymphocyte development. PMID- 7791745 TI - Modulated red blood cell survival by membrane protein clustering. AB - Human and murine blood cells treated with ZnCl2 and bis(sulfosuccinimidyl)suberate (BS3) (a cross linking agent) undergo band 3 clustering and binding of hemoglobin to red blood cell membrane proteins. These clusters induce autologous IgG binding and complement fixation, thus favouring the phagocytosis of ZnCl2/BS3 treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by changing the ZnCl2 concentration in the 0.1-1.0 mM range thus providing an effective way to affect blood cell recognition by macrophages. In fact, murine erythrocytes treated with increasing ZnCl2 concentrations have proportionally reduced survivals when reinjected into the animal. Furthermore, the organ sequestration of ZnCl2/BS3 treated cells strongly resembles the typical distribution of the senescent cells. Since the ZnCl2/BS3 treatment can also be performed on red blood cells loaded with drugs or other substances, this procedure is an effective drug-targeting system to be used for the delivery of molecules to peritoneal, liver and spleen macrophages. PMID- 7791746 TI - Na(+)-Ca2+ exchange and Ca2+ channel characteristics in bovine aorta and coronary artery smooth muscle sarcolemmal membranes. AB - Tension generation and Ca2+ flux in smooth muscle varies depending upon the diameter of a vessel and its location. The purpose of the present investigation was to determine if the biochemical characteristics of the Na(+)-Ca2+ exchanger and the Ca2+ channel differ in sarcolemmal membrane preparations isolated from a large conduit vessel (thoracic aorta) or from large and small coronary arteries. We also investigated the possibility of differences between sarcolemmal membranes isolated from coronary arteries dissected from the right and left ventricles. The purification of the sarcolemmal membranes was of a similar magnitude amongst the different groups. Contamination of the sarcolemmal membranes with other membranous organelles was negligible and similar amongst the groups. The Km and Vmax of Na(+)-dependent Ca2+ uptake in sarcolemmal vesicles was similar amongst the groups. Calcium channel characteristics were examined by measuring [3H] PN200 110 binding to sarcolemmal vesicles. The right coronary artery membranes from both large and small caliber vessels exhibited a higher Kd and the small right coronary artery sarcolemmal preparation had a lower maximal binding density for [3H] PN200-110. The results suggest that the right coronary artery, and in particular the small diameter right coronary artery, possesses altered Ca2+ channel characteristics in isolated sarcolemmal membranes. PMID- 7791747 TI - Oxidative stress adaptation improves postischemic ventricular recovery. AB - Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. In this study, the effects of myocardial adaptation to oxidative stress was examined by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic derivative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress within 1 h of treatment as evidenced by enhanced malonaldehyde formation. The oxidative stress disappeared steadily and progressively with time in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. After 24 h of endotoxin or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, compared to those at the baseline levels. Corroborating these results, both endotoxin and lipid A provided protection against myocardial ischemia and reperfusion injury as evidenced by a significantly improved postischemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adaptation to oxidative stress may be a potential tool for reduction of ischemic/reperfusion injury. PMID- 7791748 TI - Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. AB - The objective of this study was to assess the therapeutic advantage of glutathione ester along with cisplatin. Comparisons were made with renal reduced glutathione, enzymatic antioxidants, and lipid peroxidation levels. Cisplatin caused differential toxic effects on renal antioxidants and lipid peroxidation. However administration of glutathione ester modulates the toxic effects of cisplatin observed in renal antioxidants and lipid peroxidation. The finding that glutathione ester co-administration along with cisplatin is more effective and advantageous in protecting against the nephrotoxicity of cisplatin when it was given alone. PMID- 7791749 TI - Pathological changes of myocardial cytoskeleton in cardiomyopathic hamster. AB - Immunocytochemical investigation was performed on the cytoskeletal proteins in cardiac tissue of the cardiomyopathic hamster. Male cardiomyopathic UM-X7.1 hamsters at 180 days of age (n = 8) and age- and sex-matched normal BIO-RB hamsters (n = 8) were used in this study. Immunofluorescence microscopy using monoclonal antibodies against desmin, alpha-actinin, titin, and vincullin was employed. The heart weight to body weight ratio was significantly increased in the heart of cardiomyopathic hamster compared with that of normal hamster. In cardiomyopathic hamster, the left ventricular cavity was markedly dilated. Light microscopically, hypertrophy and atrophy of myocytes and myocardial fibrosis were prominently observed in cardiomyopathic myocardium. Immunocytochemically, desmin, alpha-actinin and titin showed the cross striations along the myofibers in normal myocardium. In contrast, in cardiomyopathic myocardium, desmin was irregularly distributed in myocytes and the amount of desmin was increased. Loss of cross striations of alpha-actinin and titin were frequently observed. Immunofluorescence against vinculin was not significantly altered. We conclude that the alterations of cytoskeletal proteins in myocardial cells may relate to decreased myocardial function in cardiomyopathic hamster failing heart. PMID- 7791750 TI - Renal dopamine receptors are involved in the development of cardiac hypertrophy. AB - The present study examined the effect of fenoldopam, a known dopamine-1 receptor (DA1) agonist in order to understand its involvement in the cardiac hypertrophic process. Male Sprague-Dawley rats underwent abdominal aortic constriction (AB) with placement of a suprarenal ligature while sham operated animals served as controls. The AB groups showed an increase in their heart wt, left ventricular (LV) wt, heart wt/body wt and LV wt/body ratio. Furthermore, the length of these hearts, as measured from the auriculoventricular border to the apex, LV wall and interventricular (IV) septal thickness were increased from control levels. Treatment with SCH 23390, a DA1 antagonist, on the other hand, was able to partially regress the cardiac hypertrophic changes. All these parameters were also increased in control animals treated with fenoldopam (F). Such changes were more striking in the F+AB group which showed a significant acceleration of the cardiac hypertrophic process on superimposing the two treatments. Plasma dopamine and renin activity were increased in all the groups as compared to control. These results indicate that dopamine receptors are implicated in the development of cardiac hypertrophy. PMID- 7791751 TI - Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts. AB - The objectives of this study were to determine 1) whether reactive oxygen species generated upon postischemic reperfusion lead to oxidative stress in rat hearts, and 2) whether an exogenous prooxidant present in the early phase of reperfusion causes additional injury. Isolated buffer-perfused rat hearts were subjected to 30 min of hypothermic no-flow ischemia followed by 30 min of reperfusion. Increased myocardial content of glutathione disulfide (GSSG) and increased active transport of GSSG were used as indices of oxidative stress. To impose a prooxidant load, cumene hydroperoxide (20 microM) was administered during the first 10 min of reperfusion to a separate group of postischemic hearts. Reperfusion after 30 min of hypothermic ischemia resulted in a recovery of myocardial ATP from 28% at end-ischemia to 50-60%, a release of 5% of total myocardial LDH, and an almost complete recovery of both coronary flow rate and left ventricular developed pressure. After 5 and 30 min of reperfusion, neither myocardial content of GSSG nor active transport of GSSG were increased. These indices were increased, however, if cumene hydroperoxide was administered during early reperfusion. After stopping the administration of cumene hydroperoxide, myocardial GSSG content returned to control values and GSH content increased, indicating an unimpaired glutathione reductase reaction. Despite the induction of oxidative stress, reperfusion with cumene hydroperoxide did not cause additional metabolic, structural, or functional injury when compared to reperfusion without cumene hydroperoxide. We conclude that reactive oxygen species generated upon postischemic reperfusion did not lead to oxidative stress in isolated rat hearts. Moreover, even a superimposed prooxidant load during early reperfusion did not cause additional injury. PMID- 7791754 TI - Human type II receptor for bone morphogenic proteins (BMPs): extension of the two kinase receptor model to the BMPs. AB - Bone morphogenic proteins (BMPs) are universal regulators of animal development. We report the identification and cloning of the BMP type II receptor (BMPR-II), a missing component of this receptor system in vertebrates. BMPR-II is a transmembrane serine/threonine kinase that binds BMP-2 and BMP-7 in association with multiple type I receptors, including BMPR-IA/Brk1, BMPR-IB, and ActR-I, which is also an activin type I receptor. Cloning of BMPR-II resulted from a strong interaction of its cytoplasmic domain with diverse transforming growth factor beta family type I receptor cytoplasmic domains in a yeast two-hybrid system. In mammalian cells, however, the interaction of BMPR-II is restricted to BMP type I receptors and is ligand dependent. BMPR-II binds BMP-2 and -7 on its own, but binding is enhanced by coexpression of type I BMP receptors. BMP-2 and BMP-7 can induce a transcriptional response when added to cells coexpressing ActR I and BMPR-II but not to cells expressing either receptor alone. The kinase activity of both receptors is essential for signaling. Thus, despite their ability to bind to type I and II receptors receptors separately, BMPs appear to require the cooperation of these two receptors for optimal binding and for signal transduction. The combinatorial nature of these receptors and their capacity to crosstalk with the activin receptor system may underlie the multifunctional nature of their ligands. PMID- 7791753 TI - The nerve growth factor-responsive PC12 cell line does not express the Myc dimerization partner Max. AB - Heterodimerization of Max with the nuclear oncoprotein Myc and the differentiation-associated proteins Mad and Mxi1 enables these factors to bind E box sites in DNA and control genes implicated in cell proliferation and differentiation. We show that in the PC12 pheochromocytoma tumor cell line, functional Max protein is not expressed because of the synthesis of a mutant max transcript. This transcript encodes a protein incapable of homo- or heterodimerization. Furthermore, the mutant Max protein, unlike wild-type Max, is incapable of repressing transcription from an E-box element. Synthesis of mutant max transcripts appears to be due to a homozygous chromosomal alteration within the max gene. Reintroduction of max into PC12 cells results in repression of E box-dependent transcription and a reduction in growth rate, which may explain the loss of Max expression either during the growth of the pheochromocytoma or in subsequent passage of the PC12 cell line in vitro. Finally, the ability of these cells to divide, differentiate, and apoptose in the absence of Max demonstrates for the first time that these processes can occur via Max- and possibly Myc independent mechanisms. PMID- 7791752 TI - Different roles for cyclins D1 and E in regulation of the G1-to-S transition. AB - Ectopic expression of cyclins D1 and E was previously shown to accelerate the G1/S-phase transition, indicating that both classes of G1 cyclin control an event(s) that is rate limiting for entry into S phase. In order to determine whether cyclins D1 and E control the same or two different rate-limiting events, we have created cell lines that express both cyclins in an inducible manner. We show here that ectopic expression of both cyclins E and D1 in the same cell has an additive effect on shortening of the G1 interval relative to expression of any single cyclin. In order to further explore the molecular basis for G1 cyclin action, we used cell lines capable of expressing cyclin D1, E, or both prematurely and measured the effect of cyclin expression in early G1 on phosphorylation of the retinoblastoma susceptibility gene product (pRb). We show here that while premature expression of either cyclin alone advances the G1/S phase transition to the same extent, premature expression of cyclin D1 leads to immediate appearance of hyperphosphorylated pRb, while premature expression of cyclin E does not. Ectopic expression of both cyclins E and D1 in the same cell has an additive effect on shortening of the G1 interval, while the effect on pRb phosphorylation is similar to the effect of cyclin D1 alone. These results suggest that cyclins E and D1 control two different events, both rate limiting for the G1/S-phase transition, and that pRb phosphorylation might be the rate limiting event controlled by cyclin D1. PMID- 7791756 TI - Yeast silencers can act as orientation-dependent gene inactivation centers that respond to environmental signals. AB - The mating-type loci located at the ends of chromosome III in Saccharomyces cerevisiae are transcriptionally repressed by a region-specific but sequence nonspecific silencing apparatus, mediated by cis-acting silencer sequences. Previous deletion analyses have defined the locations and organizations of the silencers in their normal context and have shown that they are composed of various combinations of replication origins and binding sites for specific DNA binding proteins. We have evaluated what organization of silencer sequences is sufficient for establishing silencing at a novel location, by inserting individual silencers next to the MAT locus and then assessing expression of MAT. The results of this analysis indicate that efficient silencing can be achieved by inserting either a single copy of the E silencer from HMR or multiple, tandem copies of either the E or I silencer from HML. These results indicate that while all silencers are functionally equivalent, they have different efficiencies; HMR E is more active than HML E, which itself is more active than HML I. Both HMR E and HML E exhibit orientation-dependent silencing, and the particular organization of binding elements within the silencer domain is critical for function. In some situations, silencing of MAT is conditional: complete silencing is obtained when cells are grown on glucose, and complete derepression occurs when cells are shifted to a nonfermentable carbon source, a process mediated in part by the RAS/cyclic AMP signaling pathway. Finally, the E silencer from HMR is able to reestablish repression immediately upon a shift back to glucose, while the silencers from HML exhibit a long lag in reestablishing repression, thus indicating distinctions between the two silencers in their reestablishment capacities. These results demonstrate that silencers can serve as nonspecific gene inactivation centers and that the attendant silencing can be rendered responsive to potential developmental cues. PMID- 7791755 TI - Identification of a mouse protein whose homolog in Saccharomyces cerevisiae is a component of the CCR4 transcriptional regulatory complex. AB - The CCR4 protein from Saccharomyces cerevisiae is a component of a multisubunit complex that is required for the regulation of a number of genes in yeast cells. We report here the identification of a mouse protein (mCAF1 [mouse CCR4 associated factor 1]) which is capable of interacting with and binding to the yeast CCR4 protein. The mCAF1 protein was shown to have significant similarity to proteins from humans, Caenorhabditis elegans, Arabidopsis thaliana, and S. cerevisiae. The yeast gene (yCAF1) had been previously cloned as the POP2 gene, which is required for expression of several genes. Both yCAF1 (POP2) and the C. elegans homolog of CAF1 were shown to genetically interact with CCR4 in vivo, and yCAF1 (POP2) physically associated with CCR4. Disruption of the CAF1 (POP2) gene in yeast cells gave phenotypes and defects in transcription similar to those observed with disruptions of CCR4, including the ability to suppress spt10 enhanced ADH2 expression. In addition, yCAF1 (POP2) when fused to LexA was capable of activating transcription. mCAF1 could also activate transcription when fused to LexA and could functionally substitute for yCAF1 in allowing ADH2 expression in an spt10 mutant background. These data imply that CAF1 is a component of the CCR4 protein complex and that this complex has retained evolutionarily conserved functions important to eukaryotic transcription. PMID- 7791758 TI - Inhibition of cellular proliferation by the Wilms' tumor suppressor WT1 is associated with suppression of insulin-like growth factor I receptor gene expression. AB - We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells. The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA). To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression. PMID- 7791757 TI - Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae. AB - The human proto-oncogene HCK encodes two versions of a protein-tyrosine kinase, with molecular weights of 59,000 (p59hck) and 61,000 (p61hck). The two proteins arise from a single mRNA by alternative initiations of translation. In this study, we explored the functions of these proteins by determining their locations within cells and by characterizing lipid modifications required for the proteins to reach those locations. We found that p59hck is entirely associated with cellular membranes, including the organelles known as caveolae; in contrast, only a portion of p61hck is situated on membranes, and none is detectable in preparations of caveolae. These distinctions can be attributed to differential modification of the two HCK proteins with fatty acids. Both proteins are at least in part myristoylated, p59hck more so than p61hck. In addition, however, p59hck is palmitoylated on cysteine 3 in the protein. Palmitoylation of the protein requires prior myristoylation and, in turn, is required for targeting to caveolae. These findings are in accord with recent reports for other members of the SRC family of protein-tyrosine kinases. Taken together, the results suggest that HCK and several of its relatives may participate in the functions of caveolae, which apparently include the transduction of signals across the plasma membrane to the interior of the cell. PMID- 7791760 TI - A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone. AB - Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone alpha-subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK cascade by an expression vector for a constitutively active form of the Raf-1 kinase led to stimulation of the alpha-subunit promoter in a concentration dependent manner. GnRH treatment was found to increase the phosphorylation of tyrosine residues of MAPK and to increase MAPK activity, as determined by an immune complex kinase assay. A reporter gene assay using the MAPK-responsive, carboxy-terminal domain of the Elk1 transcription factor was also consistent with GnRH-induced activation of MAPK. Interference with the MAPK pathway by expression vectors for kinase-defective MAPKs or vectors encoding MAPK phosphatases reduced the transcription-stimulating effects of GnRH. The DNA sequences which are required for responses to GnRH include an Ets factor-binding site. An expression vector for a dominant negative form of Ets-2 was able to reduce GnRH effects on expression of the alpha-subunit gene. These findings provide evidence that GnRH treatment leads to activation of the MAPK cascade in gonadotropes and that activation of MAPK contributes to stimulation of the alpha-subunit promoter. It is likely that an Ets factor serves as a downstream transcriptional effector of MAPK in this system. PMID- 7791759 TI - Overexpression of RelA in transgenic mouse thymocytes: specific increase in levels of the inhibitor protein I kappa B alpha. AB - RelA (p65) is one of the strongest activators of the Rel/NF-kappa B family. As a first step to elucidate the mechanisms that regulate its activity in vivo, we have generated transgenic mice overexpressing RelA in the thymus. Although the levels of RelA were significantly increased in thymocytes of transgenic mice, the overall NF-kappa B-binding activity in unstimulated cells was not augmented compared with that in control thymocytes. This could be explained by the dramatic increase of endogenous I kappa B alpha levels observed in RelA-overexpressing cells in both cytoplasmic and nuclear compartments. The ikba mRNA levels were not augmented by overexpressed RelA, but I kappa B alpha inhibitor was found to be stabilized through association with RelA. Although a fraction of RelA was associated with cytoplasmic p105, no changes in the precursor levels were observed. Upon stimulation of RelA-overexpressing thymocytes with phorbol 12 myristate 13-acetate and lectin (phytohemaglutinin), different kappa B-binding complexes, including RelA homodimers, were partially released from I kappa B alpha. Association of RelA with I kappa B alpha prevented complete degradation of the inhibitor. No effect of phorbol 12-myristate 13-acetate-lectin treatment was detected on RelA associated with p105. Our data indicate that cytoplasmic retention of overexpressed RelA by I kappa B alpha is the major in vivo mechanism controlling the potential excess of NF-kappa B activity in long-term RelA overexpressing thymocytes. PMID- 7791761 TI - Activation of retinoid X receptors induces apoptosis in HL-60 cell lines. AB - Retinoids induce myeloblastic leukemia (HL-60) cells to differentiate into granulocytes, which subsequently die by apoptosis. Retinoid action is mediated through at least two classes of nuclear receptors: retinoic acid receptors, which bind both all-trans retinoic acid and 9-cis retinoic acid, and retinoid X receptors, which bind only 9-cis retinoic acid. Using receptor-selective synthetic retinoids and HL-60 cell sublines with different retinoid responsiveness, we have investigated the contribution that each class of receptors makes to the processes of cellular differentiation and death. Our results demonstrate that ligand activation of retinoic acid receptors is sufficient to induce differentiation, whereas ligand activation of retinoid X receptors is essential for the induction of apoptosis in HL-60 cell lines. PMID- 7791763 TI - Molecular cloning of an amphibian insulin receptor substrate 1-like cDNA and involvement of phosphatidylinositol 3-kinase in insulin-induced Xenopus oocyte maturation. AB - An insulin receptor substrate 1 (IRS-1)-like cDNA was isolated from a Xenopus ovary cDNA library by low-stringency hybridization using rat IRS-1 cDNA as a probe. The deduced amino acid sequence encoded by this cDNA (termed XIRS-L) is 67% identical (77% similar) to that of rat IRS-1. Significantly, all the insulin induced tyrosine phosphorylation sites identified in rat IRS-1, including those responsible for binding to the Src homology domains of phosphatidylinositol (PI) 3-kinase, Syp and Grb2, are conserved in XIRS-L. Both mRNA and protein corresponding to the cloned XIRS-L can be detected in immature Xenopus oocytes. Recombinant XIRS-L protein produced in insect cells or a bacterial glutathione S transferase fusion protein containing the putative PI 3-kinase binding site can be phosphorylated in vitro by purified insulin receptor kinase (IRK) domain, and the IRK-catalyzed phosphorylation renders both proteins capable of binding PI 3 kinase in Xenopus oocyte lysates. Another glutathione S-transferase fusion protein containing the C terminus of XIRS-L and including several putative tyrosine phosphorylation sites is also phosphorylated by IRK in vitro, but it failed to bind PI 3-kinase. Insulin stimulation of immature Xenopus oocytes activates PI 3-kinase in vivo [as indicated by an elevation of PI(3,4)P2 and PI(3,4,5)P3] as well as oocyte maturation (as indicated by germinal vesicle breakdown). Pretreatment of these oocytes with wortmannin inhibited insulin induced activation of PI 3-kinase in vivo. The same treatment also abolished insulin-induced, but not progesterone-induced, germinal vesicle breakdown. These results (i) identify an IRS-1-like molecule in immature Xenopus oocytes, suggesting that the use of IRS-1-like Scr homology 2 domain-docking proteins in signal transduction is conserved in vertebrates, and (ii) strongly implicate PI 3 kinase as an essential effector of insulin-induced oocyte maturation. PMID- 7791764 TI - Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells. AB - T-cell receptor (TCR) cross-linking increases tyrosine phosphorylation of multiple proteins, only a few of which have been identified. One of the most rapidly tyrosine-phosphorylated polypeptides is the 120-kDa product of the proto oncogene c-cbl, a cytosolic and cytoskeletal protein containing multiple proline rich motifs that are potential binding sites for proteins containing Src homology 3 (SH3) domains. We report here that in cultured Jurkat T cells, Cbl is coprecipitated with antibody against the adapter protein Grb2. Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain. Grb2 antisera also precipitated p85 from serum-starved cells, while TCR activation increased p85 and tyrosine-phosphorylated Cbl but not Cbl protein in Grb2 immunocomplexes. Phosphatidylinositol (PI) 3-kinase activity was immunoprecipitated from serum-starved cells with Cbl and to a lesser extent with Grb2 antisera, and TCR cross-linking increased this activity severalfold. The PI 3-kinase activity associated with Cbl amounted to 5 to 10% of the total cellular activity that could be precipitated by p85 antisera. The Ras exchange factor Son of-sevenless 1 (Sos-1) was not found in anti-Cbl immunoprecipitates from activated cells, and Cbl was not detectable in anti-Sos-1 precipitates, supporting the likelihood that Sos-Grb2 and Cbl-Grb2 are present as distinct complexes. Taken together, these data suggest that Cbl function in Jurkat T cells involves its constitutive association with Grb2 and its recruitment of PI 3 kinase in response to TCR activation. PMID- 7791765 TI - Differentiation-regulated serine phosphorylation of STAT1 promotes GAF activation in macrophages. AB - Gamma interferon (IFN-gamma), a macrophage-activating cytokine, modulates gene expression through the activity of a transcription factor designated IFN-gamma activation factor (GAF). GAF is formed after phosphorylation on tyrosine and dimerization of the 91-kDa protein STAT1. We have recently reported that differentiation of the promonocytic cell line U937 into monocytes increases the amount of cellular GAF after IFN-gamma treatment and at the same time increases the phosphorylation of STAT1. Here we show that activation of the JAK family kinases, which are instrumental in mediating STAT1 phosphorylation on tyrosine, did not increase upon monocytic U937 differentiation. Consistent with this finding, levels of STAT1 tyrosine phosphorylation were virtually identical in promonocytic and monocytic U937 cells. Analysis of STAT1 phosphoamino acids and mapping of phosphopeptides showed an IFN-gamma-dependent increase in Ser phosphorylation in differentiated cells. Analyses of STAT1 isoforms by two dimensional gel electrophoresis demonstrated a differentiation-induced shift toward more acidic isoforms. All isoforms were equally sensitive to subsequent tyrosine phosphorylation, as indicated by a sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility shift typical for tyrosine-phosphorylated STAT1. Consistent with the importance of Ser phosphorylation for high-affinity binding to the IFN-gamma activation site sequence, phosphatase 2A treatment strongly reduced the formation of IFN-gamma activation site-GAF complexes in an electrophoretic mobility shift assay. Our data indicate that the activity of GAF is modulated by STAT1 serine kinases/phosphatases and suggest that this mechanism is employed in the developmental control of macrophage responsiveness to IFN gamma. PMID- 7791762 TI - Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. AB - Although many lines of evidence indicate that the cellular protein p107 is closely related to the retinoblastoma protein, the exact function of the p107 gene and its regulation are presently not known. To investigate the molecular mechanism controlling expression of the human p107 gene, a 5' flanking sequence of this gene was isolated and shown to promote high-level expression of a luciferase reporter gene in cycling human 293 and Saos-2 cells. Sequencing and transcription mapping analyses showed that the human p107 promoter is TATA-less and contains a tandem, direct repeat of E2F-binding sites, with the 3' copy overlapping the major transcription initiation site. Deletion analysis of the p107 promoter showed that a promoter DNA fragment containing only the two E2F sites together with the leader sequence could direct relatively efficient expression in 293 cells. Site-directed mutagenesis of these E2F sites revealed that although both sites were important for p107 promoter activity, mutation on the proximal, initiation site copy of the E2F site showed a stronger effect. The human p107 promoter could be repressed by the retinoblastoma protein and its own gene product. Interestingly, the repression was found to be mediated through the 5' copy of the E2F site. These studies demonstrate for the first time differential roles of two tandem E2F sites in promoter regulation. PMID- 7791766 TI - Interaction of the CCAAT displacement protein with shared regulatory elements required for transcription of paired histone genes. AB - The H2A and H2B genes of the Xenopus xlh3 histone gene cluster are transcribed in opposite directions from initiation points located approximately 235 bp apart. The close proximity of these genes to one another suggests that their expression may be controlled by either a single bidirectional promoter or by separate promoters. Our analysis of the transcription of histone gene pairs containing deletions and site-specific mutations of intergenic DNA revealed that both promoters are distinct but that they overlap physically and share multiple regulatory elements, providing a possible basis for the coordinate regulation of their in vivo activities. Using the intergenic DNA fragment as a probe and extracts from mammalian and amphibian cells, we observed the formation of a specific complex containing the CCAAT displacement protein (CDP). The formation of the CDP-containing complex was not strictly dependent on any single element in the intergenic region but instead required the presence of at least two of the three CCAAT motifs. Interestingly, similar CDP-containing complexes were formed on the promoters from the three other histone genes. The binding of CDP to histone gene promoters may contribute to the coordination of their activities during the cell cycle and early development. PMID- 7791769 TI - Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA binding protein and TFIIB. AB - Infected-cell polypeptide 4 (ICP4) of herpes simplex virus is both a transcriptional activator and a repressor. It has been previously demonstrated that both SP1-activated transcription and USF-activated transcription are repressed by ICP4 without affecting basal transcription (B. Gu, R. Rivera Gonzalez, C. A. Smith, and N. A. DeLuca, Proc. Natl. Acad. Sci. USA 90:9528-9532, 1993; R. Rivera-Gonzalez, A. N. Imbalzano, B. Gu, and N.A. DeLuca, Virology 202:550-564, 1994). In this study, it was found that ICP4 repressed the activation function of two other activators, VP16 and ICP4 itself, in vitro. ICP4 inhibited transcription by interfering with the formation of transcription initiation complexes without affecting transcription elongation. Repression of activator function required that an ICP4 DNA binding site was present in one orientation within approximately 45 bp 3' to the TATA box. DNA binding by ICP4 was necessary but not sufficient for repression. ICP4 has been shown to form tripartite complexes cooperatively with the TATA box-binding protein and TFIIB on DNA containing an ICP4 binding site and a TATA box (C. A. Smith, P. Bates, R. Rivera-Gonzalez, B. Gu, and N. DeLuca, J. Virol. 67:4676-4687, 1993). A region of ICP4 that enables the molecule to form tripartite complexes was also required in addition to the DNA binding domain for efficient repression. Moreover, repression was observed only when the ICP4 binding site was in a position that resulted in the formation of tripartite complexes. Together, the data suggest that ICP4 represses transcription by binding to DNA in a precise way so that it may interact with the basal transcription complex and inhibit some general step involved in the function of activators. The steps or interactions involved in transcriptional activation that are inhibited by ICP4 are discussed. PMID- 7791768 TI - Disturbance of normal cell cycle progression enhances the establishment of transcriptional silencing in Saccharomyces cerevisiae. AB - Previous studies have indicated that mutation of RAP1 (rap1s) or of the HMR-E silencer ARS consensus element leads to metastable repression of HMR. A number of extragenic suppressor mutations (sds, suppressors of defective silencing) that increase the fraction of repressed cells in rap1s hmr delta A strains have been identified. Here we report the cloning of three SDS genes. SDS11 is identical to SWI6, a transcriptional regulator of genes required for DNA replication and of cyclin genes. SDS12 is identical to RNR1, which encodes a subunit of ribonucleotide reductase. SDS15 is identical to CIN8, whose product is required for spindle formation. We propose that mutations in these genes improve the establishment of silencing by interfering with normal cell cycle progression. In support of this idea, we show that exposure to hydroxyurea, which increases the length of S phase, also restores silencing in rap1s hmr delta A strains. Mutations in different cyclin genes (CLN3, CLB5, and CLB2) and two cell cycle transcriptional regulators (SWI4 and MBP1) also suppress the silencing defect at HMR. The effect of these cell cycle regulators is not specific to the rap1s or hmr delta A mutation, since swi6, swi4, and clb5 mutations also suppress mutations in SIR1, another gene implicated in the establishment of silencing. Several mutations also improve the efficiency of telomeric silencing in wild-type strains, further demonstrating that disturbance of the cell cycle has a general effect on position effect repression in Saccharomyces cerevisiae. We suggest several possible models to explain this phenomenon. PMID- 7791767 TI - Functional mRNA can be generated by RNA polymerase III. AB - Eukaryotic cellular mRNA is believed to be synthesized exclusively by RNA polymerase II (pol II), whereas pol I produces long rRNAs and pol III produces 5S rRNA, tRNA, and other small RNAs. To determine whether this functional differentiation is obligatory, we examined the translational potential of an artificial pol III transcript. The coding region of the human immunodeficiency virus type 1 tat gene was placed under the control of a strong pol III promoter from the adenovirus type 2 VA RNAI gene. The resultant chimera, pVA-Tat, was transcribed accurately in vivo and in vitro and gave rise to Tat protein, which transactivated a human immunodeficiency virus-driven chloramphenicol acetyltransferase reporter construct in transfected HeLa cells. pol III-specific mutations down-regulated VA-Tat RNA production in vivo and in vitro and dramatically reduced chloramphenicol acetyltransferase transactivation. As expected for a pol III transcript, VA-Tat RNA was not detectably capped at its 5' end or polyadenylated at its 3' end, but, like mRNA, it was associated with polysomes in a salt-stable manner. Mutational analysis of a short open reading frame upstream of the Tat-coding sequence implicates scanning in the initiation of VA-Tat RNA translation despite the absence of a cap. In comparison with tat mRNA generated by pol II, VA-Tat RNA was present on smaller polysomes and was apparently translated less efficiently, which is consistent with a relatively low initiation rate. Evidently, human cells are capable of utilizing pol III transcripts as functional mRNAs, and neither a cap nor a poly(A) tail is essential for translation, although they may be stimulatory. These findings raise the possibility that some cellular mRNAs are made by pol I or pol III. PMID- 7791770 TI - Specificity of Rel-inhibitor interactions in Drosophila embryos. AB - The Rel family of transcription factors participate in a diverse array of processes, including acute responses to injury and infection, lymphocyte differentiation, and embryonic patterning. These proteins show homology in an extended region spanning about 300 amino acids (the Rel homology domain [RHD]). The RHD mediates both DNA binding and interactions with a family of inhibitor proteins, including I kappa B alpha and cactus. Previous studies have shown that an N-terminal region of the RHD (containing the sequence motif RXXRXRXXC) is important for DNA binding, while the C-terminal nuclear localization sequence is important for inhibitor interactions. Here we present a structure-function analysis of the Drosophila dorsal RHD. These studies identify another sequence within the RHD (region I) that is essential for inhibitor interactions. There is a tight correlation between the conservation of region I sequences and the specificity of Rel-inhibitor interactions in both flies and mammals. Point mutations in the region I sequence can uncouple DNA binding and inhibitor interactions in vitro. The phenotypes associated with the expression of a modified dorsal protein in transgenic Drosophila embryos suggest a similar uncoupling in vivo. Recent crystallographic studies suggest that the region I sequence and the nuclear localization sequence might form a composite surface which interacts with inhibitor proteins. PMID- 7791771 TI - Inhibition of G-protein signaling by dominant gain-of-function mutations in Sst2p, a pheromone desensitization factor in Saccharomyces cerevisiae. AB - Genetic analysis of cell-cell signaling in Saccharomyces cerevisiae has led to the identification of a novel factor, known as Sst2p, that promotes recovery after pheromone-induced growth arrest (R. K. Chan and C. A. Otte, Mol. Cell. Biol. 2:11-20, 1982). Loss-of-function mutations lead to increased pheromone sensitivity, but this phenotype is partially suppressed by overexpression of the G protein alpha subunit gene (GPA1). Suppression is allele specific, however, suggesting that there is direct interaction between the two gene products. To test this model directly, we isolated and characterized several dominant gain-of function mutants of SST2. These mutations block the normal pheromone response, including a loss of pheromone-stimulated gene transcription, cell cycle growth arrest, and G protein myristoylation. Although the SST2 mutations confer a pheromone-resistant phenotype, they do not prevent downstream activation by overexpression of G beta (STE4), a constitutively active G beta mutation (STE4Hpl), or a disruption of GPA1. None of the SST2 alleles affects the expression or stability of G alpha. These results point to the G protein alpha subunit as being the direct target of Sst2p action and underscore the importance of this novel desensitization factor in G-protein-mediated signaling. PMID- 7791774 TI - Calcium activates serum response factor-dependent transcription by a Ras- and Elk 1-independent mechanism that involves a Ca2+/calmodulin-dependent kinase. AB - Enhanced levels of cytoplasmic Ca2+ due to membrane depolarization with elevated levels of KCl or exposure to the Ca2+ ionophore ionomycin stimulate serum response element (SRE)-dependent transcription in the pheochromocytoma cell line PC12. By using altered binding specificity mutants of transcription factors that bind to the SRE, it was demonstrated that in contrast to treatment with purified growth factors, such as nerve growth factor, the serum response factor (SRF), but not Elk-1, mediates Ca(2+)-regulated SRE-dependent transcription. Enhanced levels of cytoplasmic Ca2+ were found to trigger SRE-dependent transcription via a Ras independent signaling pathway that appears to involve a Ca2+/calmodulin-dependent kinase (CaMK). Overexpression of a constitutively active form of CaMKIV stimulated SRF-dependent transcription. Taken together, these findings indicate that SRF is a versatile transcription factor that, when bound to the SRE, can function by distinct mechanisms and can mediate transcriptional responses to both CaMK- and Ras-dependent signaling pathways. PMID- 7791773 TI - A truncated K-sam product lacking the distal carboxyl-terminal portion provides a reduced level of autophosphorylation and greater resistance against induction of differentiation. AB - The K-sam gene was originally cloned from KATO-III human gastric cancer cells and is identical to the bek or keratinocyte growth factor (KGF) receptor (KGFR) or fibroblast growth factor receptor 2 gene. K-sam generates several variant transcripts by alternative splicing, and the most abundant K-sam transcript in KATO-III cells was cloned as the K-sam-IIC3 cDNA, which has the KGF-binding motif and a short carboxyl terminus lacking a putative phospholipase C-gamma 1 association site, Tyr-769. The K-sam-IIC3 cDNA was distinct from the K-sam-IIC1 cDNA, which was the same as the previously reported KGFR cDNA. The K-sam-IIC1 product contains a long carboxyl terminus with Tyr-769. K-sam-IIC3 showed greater transforming activity in NIH 3T3 cells than did K-sam-IIC1, and in gastric cancer cell lines in general, the level of K-sam-IIC3 mRNA was greater than that of K sam-IIC1 mRNA. Here we report that the K-sam-IIC3 product was less autophosphorylated than the K-sam-IIC1 product in NIH 3T3 transfectants. K-sam IIC3-transfected keratinocytes showed a stronger mitogenic response to KGF than did K-sam-IIC1 transfectants. Moreover, K-sam-IIC3-transfected L6 myoblast cells hardly differentiated when cultured in differentiation-inducing medium and growth was not significantly affected, while K-sam-IIC1 transfectants showed a differentiated phenotype with a reduced growth rate. These data indicate the difference in the signal transduction mediated by two KGFR-type K-sam variants generated by alternative splicing which might be involved in certain differentiation and carcinogenesis scenarios. PMID- 7791772 TI - Ras transformation results in an elevated level of cyclin D1 and acceleration of G1 progression in NIH 3T3 cells. AB - Ectopic overexpression of v-H-Ras protein in NIH 3T3 cells resulted in cellular transformation and an acceleration of G1 progression of these cells. A shortened G1 phase was found to be associated with an increased level of cyclin D1 but not cyclin E protein. Using an antisense blocking method, reduced synthesis of cyclin D1 in v-H-Ras transformants resulted in a slower G1 progression rate of these cells. Although constitutive overexpression of cyclin D1 in NIH 3T3 cells accelerated G1 progression, cells remained untransformed. Furthermore, inhibition of cyclin D1 synthesis greatly impaired the soft-agar cloning efficiency of v-H Ras transformants. These results suggest that increased expression of cyclin D1 is necessary but not sufficient for the transforming activity of v-H-Ras. Similar effect on cell cycle progression was also observed in Raf-transformed cells. In addition to cyclin D1, cyclin E protein was found to be elevated in Src transformants. This may account for the further shortening of the G1 phase of these cells. Activation of an additional Ras-independent pathway was suggested to be responsible for the further acceleration of the G1 phase in Src transformants. PMID- 7791775 TI - Bdf1, a yeast chromosomal protein required for sporulation. AB - The BDF1 gene of Saccharomyces cerevisiae is required for sporulation. Under starvation conditions, most cells from the bdf1 null mutant fail to undergo one or both meiotic divisions, and there is an absolute defect in spore formation. The Bdf1 protein localizes to the nucleus throughout all stages of the mitotic and meiotic cell cycles. Analysis of spread meiotic nuclei reveals that the Bdf1 protein is localized fairly uniformly along chromosomes, except that it is excluded specifically from the nucleolus. A bdf1 null mutant displays a reduced rate of vegetative growth and sensitivity to a DNA-damaging agent. The BDF1 gene encodes a 77-kDa protein that contains two bromodomains, sequence motifs of unknown function. Separation-of-function alleles suggest that only one of the two bromodomains is required for sporulation, whereas both are required for Bdf1 function in vegetative cells. We propose that the Bdf1 protein is a component of chromatin and that the mitotic and meiotic defects of the bdf1 null mutant result from alterations in chromatin structure. PMID- 7791777 TI - Role of heat shock cognate 70 protein in import of ornithine transcarbamylase precursor into mammalian mitochondria. AB - The roles of the 70-kDa cytosolic heat shock protein (hsp70) in import of precursor proteins into the mitochondria were postulated to be related to (i) unfolding of precursor proteins in the cytosol, (ii) maintenance of the import competent state, and (iii) unfolding and transport of precursor proteins through contact sites, in cooperation with matrix hsp70. We examined roles of cytosolic hsp70 family members in import of ornithine transcarbamylase precursor (pOTC) into rat liver mitochondria, using an in vitro import system and antibodies against hsp70. Immunoblot analysis using an hsc70 (70-kDa heat shock cognate protein)-specific monoclonal antibody and a polyclonal antibody that reacts with both hsc70 and hsp70 showed that hsc70 is the only or major form of hsp70 family members in the rabbit reticulocyte lysate. The hsc70 antibody did not inhibit pOTC import when added prior to import assay. However, when pOTC was synthesized in the presence of the antibody and then subjected to import assay, pOTC import was markedly decreased. pOTC import was also decreased when the precursor was synthesized in the lysate depleted for hsc70 by treatment with hsc70 antibody conjugated Sepharose. This reduction was almost completely restored by readdition of purified mouse hsc70 during pOTC synthesis. The readdition of hsc70 after pOTC synthesis and only during the import assay was not effective. Thus, once import competence of pOTC was lost, hsc70 was ineffective for restoration. Newly synthesized pOTC lost import competence in the absence of hsc70 somewhat more rapidly than in its presence. These results indicate that hsc70 is required during pOTC synthesis and not during import into the mitochondria. hsc70 presumably binds to pOTC polypeptide and maintains it in an import-competent form. PMID- 7791776 TI - Characterization of fus1 of Schizosaccharomyces pombe: a developmentally controlled function needed for conjugation. AB - In Schizosaccharomyces pombe, the fus1 mutation blocks conjugation at a point after cell contact and agglutination. The cell walls separating the mating partners are not degraded, which prevents cytoplasmic fusion. In order to investigate the molecular mechanism of conjugation, we cloned the fus1 gene and found that it is capable of encoding a 1,372-amino-acid protein with no significant similarities to other known proteins. Expression of the fus1 gene is regulated by the developmental state of the cells. Transcription is induced by nitrogen starvation and requires a pheromone signal in both P and M cell types. Consequently, mutants defective in the pheromone response pathway fail to induce fus1 expression. The ste11 gene, which encodes a transcription factor controlling expression of many genes involved in sexual differentiation, is also required for transcription of fus1. Furthermore, deletion of two potential Ste11 recognition sites in the fus1 promoter region abolished transcription, and expression could be restored when we inserted a different Ste11 site from the mat1-P promoter. Since this element was inverted relative to the fus1 element, we conclude that activation of transcription by Ste11 is independent of orientation. Although the fus1 mutant has a phenotype very similar to that of Saccharomyces cerevisiae fus1 mutants, the two proteins appear to have different roles in the process of cell fusion. Budding yeast Fus1 is a typical membrane protein and contains an SH3 domain. Fission yeast Fus1 has no features of a membrane protein, yet it appears to localize to the projection tip. A characteristic proline-rich potential SH3 binding site may mediate interaction with other proteins. PMID- 7791779 TI - A UV-responsive G2 checkpoint in rodent cells. AB - We have studied the effect of UV irradiation on the cell cycle progression of synchronized Chinese hamster ovary cells. Synchronization of cells in S or G2 phase was accomplished by the development of a novel protocol using mimosine, which blocks cell cycle progression at the G1/S boundary. After removal of mimosine, cells proceed synchronously through the S and G2 phases, allowing manipulation of cells at specific points in either phase. Synchronization of cells in G1 was achieved by release of cells after a period of serum starvation. Cells synchronized by these methods were UV irradiated at defined points in G1, S, and G2, and their subsequent progression through the cell cycle was monitored. UV irradiation of G1-synchronized cells caused a dose-dependent delay in entry into S phase. Irradiation of S-phase-synchronized cells inhibited progression through S phase and then resulted in accumulation of cells for a prolonged interval in G2. Apoptosis of a subpopulation of cells during this extended period was noted. UV irradiation of G2-synchronized cells caused a shorter G2 arrest. The arrest itself and its duration were dependent upon the timing (within G2 phase) of the irradiation and the UV dose, respectively. We have thus defined a previously undescribed (in mammalian cells) UV-responsive checkpoint in G2 phase. The implications of these findings with respect to DNA metabolism are discussed. PMID- 7791778 TI - Dioxin induces localized, graded changes in chromatin structure: implications for Cyp1A1 gene transcription. AB - In mouse hepatoma cells, the environmental contaminant 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD, or dioxin) induces Cyp1A1 gene transcription, a process that requires two basic helix-loop-helix regulatory proteins, the aromatic hydrocarbon receptor (AhR) and the aromatic hydrocarbon receptor nuclear translocator (Arnt). We have used a ligation-mediated PCR technique to analyze dioxin-induced changes in protein-DNA interactions and chromatin structure of the Cyp1A1 enhancer promoter in its native chromosomal setting. Dioxin-induced binding of the AhR/Arnt heteromer to enhancer chromatin is associated with a localized (about 200 bp) alteration in chromatin structure that is manifested by increased accessibility of the DNA; these changes probably reflect direct disruption of a nucleosome by AhR/Arnt. Dioxin induces analogous AhR/Arnt-dependent changes in chromatin structure and accessibility at the Cyp1A1 promoter. However, the changes at the promoter must occur by a different, more indirect mechanism, because they are induced from a distance and do not reflect a local effect of AhR/Arnt binding. Dose-response experiments indicate that the changes in chromatin structure at the enhancer and promoter are graded and mirror the graded induction of Cyp1A1 transcription by dioxin. We discuss these results in terms of a TCDD-induced shift in an equilibrium between nucleosomal and nonnucleosomal chromatin configurations. PMID- 7791780 TI - Gene-specific and strand-specific DNA repair in the G1 and G2 phases of the cell cycle. AB - We have analyzed the fine structure of DNA repair in Chinese hamster ovary (CHO) cells within the G1 and G2 phases of the cell cycle. Repair of inactive regions of the genome has been suggested to increase in the G2 phase of the cell cycle compared with other phases. However, detailed studies of DNA repair in the G2 phase of the cell cycle have been hampered by technical limitations. We have used a novel synchronization protocol (D. K. Orren, L. N. Petersen, and V. A. Bohr, Mol. Cell. Biol. 15:3722-3730, 1995) which permitted detailed studies of the fine structure of DNA repair in G2. CHO cells were synchronized and UV irradiated in G1 or early G2. The rate and extent of removal of cyclobutane pyrimidine dimers from an inactive region of the genome and from both strands of the actively transcribed dihydrofolate reductase (DHFR) gene were examined within each phase. The repair of the transcribed strand of the DHFR gene was efficient in both G1 and G2, with no major differences between the two cell cycle phases. Neither the nontranscribed strand of the DHFR gene nor an inactive region of the genome was repaired in G1 or G2. CHO cells irradiated early in G2 were more resistant to UV irradiation than cells irradiated in late G1. Since we found no major difference in repair rates in G1 and G2, we suggest that G2 resistance can be attributed to the increased time (G2 and G1) available for repair before cells commit to DNA synthesis. PMID- 7791782 TI - Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron. AB - Constitutive expression of c-Fos, FosB, Fra-1, or c-Jun in rat fibroblasts leads to up-regulation of the immediate-early gene fra-1. Using the posttranslational FosER induction system, we demonstrate that this AP-1-dependent stimulation of fra-1 expression is rapid, depends on a functional DNA-binding domain of FosER, and is a general phenomenon observed in different cell types. In vitro mutagenesis and functional analysis of the rat fra-1 gene in stably transfected Rat-1A-FosER fibroblasts indicated that basal and AP-1-regulated expression of the fra-1 gene depends on regulatory sequences in the first intron which comprise a consensus AP-1 site and two AP-1-like elements. We have also investigated the transactivating and transforming properties of the Fra-1 protein to address the significance of fra-1 up-regulation. The entire Fra-1 protein fused to the DNA binding domain of Ga14 is shown to lack any transactivation function, and yet it possesses oncogenic potential, as overexpression of Fra-1 in established rat fibroblasts results in anchorage-independent growth in vitro and tumor development in athymic mice, fra-1 is therefore not only induced by members of the Fos family, but its gene product may also contribute to cellular transformation by these proteins. Together, these data identify fra-1 as a unique member of the fos gene family which is under positive control by AP-1 activity. PMID- 7791781 TI - Functional interaction between the POU domain protein Tst-1/Oct-6 and the high mobility-group protein HMG-I/Y. AB - The POU domain protein Tst-1/Oct-6 is a transcriptional activator of human papovavirus JC virus in transient transfections. Because of its endogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. Activation of viral early and late genes depends on the ability of Tst-1/Oct-6 to interact with an AT rich element within the viral regulatory region. Here, we show that this element not only is bound by Tst-1/Oct-6 but, in addition, serves as a binding site for the high-mobility-group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct-6 binding was observed on a site that did not allow binding of HMG-I/Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. These results point to an accessory role for HMG I/Y in the activation of JC viral gene expression by the POU domain protein Tst 1/Oct-6. In agreement with such a role, HMG-Y synergistically supported the function of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y. PMID- 7791784 TI - The EGP1 gene may be a positive regulator of protein phosphatase type 1 in the growth control of Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae GLC7 gene encodes the catalytic subunit of type 1 protein phosphatase (PP1) and is required for cell growth. A cold-sensitive glc7 mutant (glc7Y170) arrests in G2/M but remains viable at the restrictive temperature. In an effort to identify additional gene products that function in concert with PP1 to regulate growth, we isolated a mutation (gpp1) that exacerbated the growth phenotype of the glc7Y170 mutation, resulting in rapid death of the double mutant at the nonpermissive temperature. We identified an additional gene, EGP1, as an extra-copy suppressor of the glc7Y170 gpp1-1 double mutant. The nucleotide sequence of EGP1 predicts a leucine-rich repeat protein that is similar to Sds22, a protein from the fission yeast Schizosaccharomyces pombe that positively modulates PP1. EGP1 is essential for cell growth but becomes dispensable upon overexpression of the GLC7 gene. Egp1 and PP1 directly interact, as assayed by coimmunoprecipitation. These results suggest that Egp1 functions as a positive modulator of PP1 in the growth control of S. cerevisiae. PMID- 7791783 TI - A gene that is related to SRY and is expressed in the testes encodes a leucine zipper-containing protein. AB - SRY-related cDNA encoding a protein with a high-mobility-group (HMG) box and a leucine zipper motif, which was designated SOX-LZ, was isolated from a rainbow trout testis cDNA library. Comparison of this cDNA with the mouse homologous cDNA isolated from a testis cDNA library exhibits an overall amino acid sequence identity of 77%, which is in striking contrast to the abrupt loss of amino acid sequence homology outside the HMG box found among mammalian SRY genes. In both rainbow trout and mice, Northern (RNA) blot analyses have revealed the presence of a testis-specific 3-kb-long SOX-LZ mRNA, and this transcript appeared coincidentally with the protamine mRNA, suggesting its expression in the germ line. A recombinant HMG box region protein encoded by SOX-LZ could bind strongly with an oligonucleotide containing an AACAAT sequence, which is also recognized by mouse Sry and Sox-5. Upon cotransfection into CHO cells, SOX-LZ transactivated transcription through its binding motif when the region including the leucine zipper motif was deleted [SOX-LZ (D105-356)]; however, the intact SOX-LZ failed to transactivate. The intact SOX-LZ could form homodimers through the leucine zipper, which resulted in inhibition of DNA binding by the HMG box, while SOX-LZ (D105-356), which was incapable of dimerization, showed specific binding with the AACAAT sequence. Thus, the repressed transactivation of the intact SOX-LZ in CHO cells was primarily attributable to the low level of DNA binding of SOX-LZ homodimers. PMID- 7791785 TI - The Saccharomyces cerevisiae gene SDS22 encodes a potential regulator of the mitotic function of yeast type 1 protein phosphatase. AB - In higher eukaryotes, the activity and specificity of the type 1 protein serine threonine phosphatase (PP1) catalytic subunit is thought to be controlled by its association with a number of regulatory or targeting subunits. Here we describe the characterization of a gene encoding one such potential polypeptide in the yeast Saccharomyces cerevisiae. The gene which we have isolated (termed SDS22) encodes a product with a high degree of sequence identity to the fission yeast sds22 protein, a known regulator of the mitotic function of PP1 in Schizosaccharomyces pombe. Using two different criteria, we have demonstrated that Sds22p and the catalytic subunit of PP1 (Glc7p) interact in yeast cells. We have also generated a temperature-sensitive allele of GLC7 (glc7-12) which causes a block to the completion of mitosis at the restrictive temperature. Additional copies of SDS22 lead to allele-specific suppression of the glc7-12 mutant, strongly suggesting that the interaction between the two proteins is of functional significance. Sds22p is therefore likely to be the second example of a PP1 regulatory subunit identified in S. cerevisiae. PMID- 7791786 TI - Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the products of multiple murine Hox genes, some of which are themselves oncogenes. AB - E2A-PBX1 is the oncogene produced at the t(1;19) chromosomal breakpoint of pediatric pre-B-cell leukemia. Expression of E2A-Pbx1 induces fibroblast transformation and myeloid and T-cell leukemia in mice and arrests differentiation of granulocyte macrophage colony-stimulating factor-dependent myeloblasts in cultured marrow. Recently, the Drosophila melanogaster protein Exd, which is highly related to Pbx1, was shown to bind DNA cooperatively with the Drosophila homeodomain proteins Ubx and Abd-A. Here, we demonstrate that the normal Pbx1 homeodomain protein, as well as its oncogenic derivative, E2A-Pbx1, binds the DNA sequence ATCAATCAA cooperatively with the murine Hox-A5, Hox-B7, Hox-B8, and Hox-C8 homeodomain proteins, which are themselves known oncoproteins, as well as with the Hox-D4 homeodomain protein. Cooperative binding to ATCAATCAA required the homeodomain-dependent DNA-binding activities of both Pbx1 and the Hox partner. In cotransfection assays, Hox-B8 suppressed transactivation by E2A Pbx1. These results suggest that (i) Pbx1 may participate in the normal regulation of Hox target gene transcription in vivo and therein contribute to aspects of anterior-posterior patterning and structural development in vertebrates, (ii) that E2A-Pbx1 could abrogate normal differentiation by altering the transcriptional regulation of Hox target genes in conjunction with Hox proteins, and (iii) that the oncogenic mechanism of certain Hox proteins may require their physical interaction with Pbx1 as a cooperating, DNA-binding partner. PMID- 7791787 TI - Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation. AB - eps8, a recently identified tyrosine kinase substrate, has been shown to augment epidermal growth factor (EGF) responsiveness, implicating it in EGF receptor (EGFR)-mediated mitogenic signaling. We investigated the status of eps8 phosphorylation in normal and transformed cells and the role of eps8 in transformation. In NIH 3T3 cells overexpressing EGFR (NIH-EGFR), eps8 becomes rapidly phosphorylated upon EGF stimulation. At receptor-saturating doses of EGF, approximately 30% of the eps8 pool is tyrosine phosphorylated. Under physiological conditions of activation (i.e., at low receptor occupancy), corresponding to the 50% effective dose of EGF for mitogenesis, approximately 3 to 4% of the eps8 contains phosphotyrosine. In human tumor cell lines, we detected constitutive tyrosine phosphorylation of eps8, with a stoichiometry (approximately 5%) similar to that associated with potent mitogenic response in NIH-EGFR cells. Overexpression of eps8 was able to transform NIH 3T3 cells under limiting conditions of activation of the EGFR pathway. Concomitant tyrosine phosphorylation of eps8 and shc, but not of rasGAP, phospholipase C-gamma, and eps15, was frequently detected in tumor cells. This suggested that eps8 and shc might be part of a pathway which is preferentially selected in some tumors. Cooperation between these two transducers was further indicated by the finding of their in vivo association. This association was, at least in part, dependent on recognition of shc by the SH3 domain of eps8. Our results indicate that eps8 is physiologically part of the EGFR-activated signaling and that its alterations can contribute to the malignant phenotype. PMID- 7791789 TI - MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation. AB - The terminal differentiation of C2C12 skeletal muscle cells involves the activation of unique sets of genes and an irreversible withdrawal from the cell cycle. This process is associated with a decrease in cdk2 activity in cell extracts. The decrease in cdk2 activity correlates with diminished levels of cdk2 and cyclin A and with a marked induction of the p21 cyclin-dependent kinase (cdk) inhibitor. The upregulation of p21 occurred at the levels of mRNA and protein, and p21 formed a complex with the cyclin kinases in myotubes. Further, the immunodepletion of p21 from myotube extracts neutralized the heat-stable cdk2 inhibitory activity that was induced upon myogenic differentiation. The levels of p21 mRNA, protein, and activity remained constant in myotubes when they were reexposed to mitogen-rich growth medium, indicating that permanent changes in the cell's genetic program contribute to its sustained expression following terminal differentiation. Indeed, 10T1/2 fibroblasts transformed with the myogenic factor MyoD, but not the parental multipotent cells, upregulated p21 transcript levels when induced to differentiate by serum withdrawal, demonstrating that the upregulation is an integral feature of myogenic commitment and differentiation. The functional consequences of this upregulation were indicated by ectopically expressing p21 in myoblasts; this was sufficient for cell cycle arrest in mitogen rich growth medium. The induction and sustained expression of p21 appears to be a contributory mechanism by which myocytes irreversibly exit the cell cycle upon terminal differentiation. PMID- 7791788 TI - Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system. AB - With modified two-hybrid technology, we have isolated a member of a new family of basic helix-loop-helix (bHLH) transcription factors. Thing1 (Th1) was identified in a screen of a mouse embryo cDNA library as a partner for the Drosophila E protein daughterless. RNA in situ hybridization and reverse transcriptase-PCR demonstrate a stage- and tissue-specific distribution for the expression of Th1. Although tissue specific, the expression pattern of Th1 is fairly complex. During development, Th1 mRNA is widely expressed in extraembryonic tissues, portions of the heart, autonomic ganglia, the gut, and pharyngeal arches. At embryonic day 7.5 (E7.5), extraembryonic derivatives show robust Th1 expression. By E8.5, expression in the embryonic heart becomes detectable. During the next 2 days of development, the signal also includes gut and pharyngeal arches. Predominant expression at E13.5 is in neural crest derivatives, especially the autonomic nervous system and adrenal medulla. Expression of Th1 persists in the adult, in which it is localized to the smooth muscle cells of the gut. In vitro, Th1 protein recognizes a set of DNA sites that are more degenerate than has been determined for other bHLH factors, indicating a reduced binding specificity. Transient transfection of NIH 3T3 cells with GAL4-Th1 fusions reveals a repression activity mediated by the Th1 bHLH domain. In combination, these properties define Th1 as a new bHLH protein with a unique set of properties. PMID- 7791791 TI - Pi 1 binding sites are negative regulators of bcl-2 expression in pre-B cells. AB - The bcl-2 gene is differentially regulated during B-cell development, with low level expression in pre-B cells and higher-level expression in mature B cells. These changes correlate with susceptibility to cell death by apoptosis and suggest that the Bcl-2 protein may play a role in the control of cell death during B-cell development. We have identified two negative regulatory regions in the human bcl-2 5' flanking and 5' untranslated regions in pre-B cells; these regions have no significant function in mature B cells. Further investigation of these regions revealed two pre-B-cell-specific enhancer elements (pi 1 sites) in the 5' negative regulatory region and one in the 3' negative regulatory region. Mutational analysis confirmed that these three sites functioned as negative regulators of the bcl-2 promoter in the pre-B-cell line Nalm-6. Electrophoretic mobility shift assays with each of the three sites demonstrated a complex of identical mobility to that formed with the immunoglobulin heavy-chain enhancer pi 1 site. UV cross-linking experiments revealed that a protein with a molecular mass of 58 kDa bound to the three bcl-2 sites and to the immunoglobulin enhancer site. This protein reacted with an antibody against Ets family proteins. Constructs with the isolated pi 1 sites linked to the simian virus 40 promoter were used in transient transfection experiments in the pre-B-cell line. The bcl-2 sites decreased expression of the simian virus 40 promoter, while the immunoglobulin enhancer site increased its expression. The pi 1 sites in the bcl 2 gene may play a role in the developmental regulation of bcl-2 expression during B-cell differentiation. PMID- 7791790 TI - Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins. AB - Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of this family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and phorbol-12-myristate-13-acetate (PMA)-A23187 stimulation are necessary for IL-5 promoter activation. The requirement for another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNAs of three GATA-binding proteins, hGATA-2, hGATA-3, and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms a specific DNA-protein complex with the -70 GATA site. An electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity for the -70 GATA site among the three GATA-binding proteins. When the transactivation abilities were compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed. PMID- 7791792 TI - Characterization of a mutant calcineurin A alpha gene expressed by EL4 lymphoma cells. AB - The calmodulin-stimulated phosphatase calcineurin plays a critical role in calcium-dependent T-lymphocyte activation pathways. Here, we report the identification of a missense mutation in the calcineurin A alpha gene expressed by EL4 T-lymphoma cells. This mutation changes an evolutionarily conserved aspartic acid to asparagine within the autoinhibitory domain of the calcineurin A alpha protein. A comparison of wild-type and mutant autoinhibitory peptides indicates that this amino acid substitution greatly reduces inhibition of calcineurin phosphatase activity. Additional peptide inhibition studies support a pseudosubstrate model of autoinhibitory function, in which the conserved aspartic acid residue may serve as a molecular mimic of either phosphoserine or phosphothreonine. Expression of the mutant calcineurin appears to affect cellular signal transduction pathways, as EL4 cells can be activated by suboptimal concentrations of calcium ionophore in the presence of phorbol esters. Moreover, this phenotype can be transferred to Jurkat T cells by transfection of the mutated calcineurin gene. These findings implicate a conserved aspartic acid in the mechanism of calcineurin autoinhibition and suggest that mutation of this residue is associated with aberrant calcium-dependent signaling in vivo. PMID- 7791793 TI - Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. AB - Hepatitis B virus S transcripts contain a region, known as the posttranscriptional regulatory element (PRE), that activates their transport from the nucleus to the cytoplasm. J. Huang and T. J. Liang (Mol. Cell. Biol. 13:7476 7486, 1993) have shown that this element can partially substitute for the human immunodeficiency virus Rev-response element (RRE) in a reporter plasmid that is dependent on the RRE and Rev protein for expression and concluded that PRE exhibits Rev-RRE-like functions by inhibiting splicing. However, we have obtained additional data which indicate that the PRE functions in a novel manner that is not dependent on inhibition of splicing. Unlike Rev-RRE, the PRE functions independently of splice donor and acceptor sites and can activate cytoplasmic expression of an intronless (so-called prespliced) beta-globin transcript. Conversely, a heterologous intron can substitute for the PRE in increasing cytoplasmic expression of hepatitis B virus S transcripts. In addition, the host nuclear factor, YL2 (p32), which enhances Rev-RRE function has no effect on PRE dependent gene expression. Since S transcripts are not normally known to be spliced and since RNA splicing and cytoplasmic transport are tightly linked processes in higher eucaryotic cells, we conclude that the PRE functions in cis to allow the export of nuclear transcripts that do not interact efficiently with the splicing pathway and hence are normally not exported well from the nucleus. Such elements are critical for the life cycle of viruses, such as hepatitis B virus, which undergo reverse transcription during replication. PMID- 7791795 TI - Role of cysteine residues in regulation of p53 function. AB - Previous studies of p53 have implicated cysteine residues in site-specific DNA binding via zinc coordination and redox regulation (P. Hainaut and J. Milner, Cancer Res. 53:4469-4473, 1993; T. R. Hupp, D. W. Meek, C. A. Midgley, and D. P. Lane, Nucleic Acids Res. 21:3167-3174, 1993). We show here that zinc binding and redox regulation are, at least in part, distinct determinants of the binding of p53 to DNA. Moreover, by substituting serine for each cysteine in murine p53, we have investigated the roles of individual cysteines in the regulation of p53 function. Substitution of serine for cysteine at position 40, 179, 274, 293, or 308 had little or no effect on p53 function. In contrast, replacement of cysteine at position 173, 235, or 239 markedly reduced in vitro DNA binding, completely blocked transcriptional activation, and led to a striking enhancement rather than a suppression of transformation by p53. These three cysteines have been implicated in zinc binding by X-ray diffraction studies (Y. Cho, S. Gorina, P.D. Jeffrey, and N.P. Pavletich, Science 265:346-355, 1994); our studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to bind zinc. Lastly, substitutions for cysteines at position 121, 132, 138, or 272 partially blocked both transactivation and the suppression of transformation by p53. These four cysteines are located in the loop-sheet-helix region of the site-specific DNA binding domain of p53. Like the cysteines in the zinc-binding region, therefore, these cysteines may cooperate to modulate the structure of the DNA-binding domain. Our findings argue that p53 is subject to more than one level of conformational modulation through oxidation-reduction of cysteines at or near the p53-DNA interface. PMID- 7791796 TI - Homologous DNA sequences and cellular factors are implicated in the control of glucagon and insulin gene expression. AB - The glucagon gene is specifically expressed in the alpha cells of pancreatic islets. The promoter of the glucagon gene is responsible for this specificity. Within the promoter, the upstream promoter element G1 is critical to restrict expression to the alpha cells. We define here a composite DNA control element, G4, localized upstream of G1 between nucleotides -100 and -140 which functions as an islet-specific activator in both glucagon- and insulin-producing cells but not in nonislet cells. G4 contains at least three protein binding sites. The most proximal site, E2, is highly homologous to the E1, SMS-UE, and B elements of the rat insulin I, somastatin, and elastase I genes, respectively, and interacts with a pancreas-specific complex; the distal site, E3, represents an E box which is identical to the E boxes of the rat insulin I and II genes and binds to a complex similar or identical to IEF1 which has been implicated in the tissue-specific control of insulin gene expression. These two sites necessitate a third element, the intervening sequence, to activate transcription. We conclude that the first 140 bp of the glucagon gene promoter contains at least two DNA control elements responsible for pancreatic alpha-cell-specific expression: G4, an islet cell specific element sharing common binding sites with the insulin gene, and G1, which restricts glucagon gene expression to the alpha cells. This double control of specificity might have relevance during islet cell differentiation. PMID- 7791794 TI - Characterization of promoter elements required for cell-specific expression of the neurotensin/neuromedin N gene in a human endocrine cell line. AB - Expression of the gene encoding neurotensin/neuromedin N (NT/N) is mostly limited to the brain and specialized enteroendocrine cells (N cells) of the distal small intestine. We have analyzed the NT/N DNA sequences upstream of the RNA start site that direct cell-specific expression using a novel human endocrine cell line, BON, that resembles intestinal N cells in several important aspects, including NT/N precursor protein processing, ratios of different NT/N mRNA forms, and high levels of constitutive expression of the NT/N gene. Transient transfection assays with plasmids with progressive 5' deletions of the rat NT/N promoter identified the proximal 216 bp of 5' flanking sequences as essential for high-level constitutive NT/N expression in BON cells. In addition, a detailed mutational analysis defined multiple regions within the proximal 216 bp that contribute to cell-specific NT/N expression. These elements include a proximal cyclic AMP response element (CRE)/AP-1-like motif (TGACATCA) that binds c-Jun, JunD, CRE binding (CREB), and ATF proteins, a near-consensus glucocorticoid response element, and a distal consensus AP-1 site that binds c-Fos, Fra-1, and JunD. In addition, elements contained within two 21-bp imperfect direct repeats play an important role in NT/N expression in BON cells and may bind novel factors that act as positive regulators of NT/N expression. DNase I footprinting and gel shift analyses demonstrate that the sites identified by mutational analysis, and at least one additional site, specifically bind BON cell nuclear proteins in vitro. We speculate that a complex pattern of regulation requiring interaction between a proximal CRE/AP-1-like motif and other upstream control elements play an important role in the high-level constitutive expression of NT/N in the human endocrine cell line BON. In addition, the BON cell line provides a unique model to further characterize the factors regulating cell-specific NT/N expression and to better understand the mechanisms responsible for the terminal differentiation of the N-cell lineage in the gut. PMID- 7791797 TI - Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. AB - Hsp90 is a protein chaperone whose functions are focused on a specific set of target proteins. The nature of Hsp90's interactions with these proteins is poorly understood. To provide tools for examining these interactions, we have isolated eight broadly distributed temperature-sensitive (ts) point mutations in the Hsp90 gene (HSP82) of Saccharomyces cerevisiae. The mutants fall into two distinct classes. One has a classic ts phenotype, with nearly wild-type activity at 25 degrees C and a precipitous loss of function at 34 degrees C. The remaining seven mutants, in contrast, cause a general reduction in Hsp90 function and are ts because they do not provide the high level of function required for growth at high temperatures. The effects of these mutants on two target proteins, a transcription factor (glucocorticoid receptor) and a tyrosine kinase (pp60v-src), provided several insights on Hsp90 function. First, Hsp90 is not only required to help the glucocorticoid receptor achieve a hormone-activable state, it is continuously required to maintain that state. Second, Hsp90's function in the maturation of pp60v-src involves separable roles in protein accumulation and kinase activation. Thus, Hsp90 is an integral component of both the steroid receptor and kinase signaling pathways. Finally, all eight point mutants affect the activation of both the glucocorticoid receptor and pp60v-src, indicating that Hsp90 promotes the activity of these very different target proteins through common mechanisms. PMID- 7791798 TI - Cyclin E restores p53 activity in contact-inhibited cells. AB - The wild-type p53 protein is a potent growth suppressor when overexpressed in vitro. It functions as a transcriptional activator and causes growth arrest at the G1/S stage of the cell cycle. We monitored p53 transactivation as an indicator of p53 function throughout the cell cycle. We first demonstrate that cells which exhibited contact inhibition of growth lacked p53 transactivation function at high cell density. Since these cells were noncycling, we examined whether the ectopic expression of any cyclin could override contact inhibition of growth and restore p53 transactivation function. The transfection of cyclin E at high cell density stimulated the progression of cells through the cell cycle and restored p53 transactivation function. The transcriptional activity of p53 induced by cyclin E was regulated at the level of DNA binding. Cells that did not show contact inhibition of growth had a functional p53 regardless of cell density. Thus, contact inhibition of cell growth corresponded to a lack of p53 transactivation function and the overexpression of cyclin E in these contact inhibited cells stimulated cell cycle progression and resulted in p53 transcriptional activity. PMID- 7791799 TI - A 15-base-pair element activates the SPS4 gene midway through sporulation in Saccharomyces cerevisiae. AB - Sporulation of the yeast Saccharomyces cerevisiae represents a simple developmental process in which the events of meiosis and spore wall formation are accompanied by the sequential activation of temporally distinct classes of genes. In this study, we have examined expression of the SPS4 gene, which belongs to a group of genes that is activated midway through sporulation. We mapped the upstream boundary of the regulatory region of SPS4 by monitoring the effect of sequential deletions of 5'-flanking sequence on expression of plasmid-borne versions of SPS4 introduced into a MATa/MAT alpha delta sps4/delta sps4 strain. This analysis indicated that the 5' boundary of the regulatory region was within 50 bp of the putative TATA box of the gene. By testing various oligonucleotides that spanned this boundary and the downstream sequence for their ability to activate expression of a heterologous promoter, we found that a 15-bp sequence sufficed to act as a sporulation-specific upstream activation sequence. This 15 bp fragment, designated UASSPS4, activated expression of a CYC1-lacZ reporter gene midway through sporulation and was equally active in both orientations. Extending the UAS fragment to include the adjacent 14-bp enhanced its activity 10 fold. We show that expression of SPS4 is regulated in a manner distinct from that of early meiotic genes: mutation of UME6 did not lead to vegetative expression of SPS4, and sporulation-specific expression was delayed by mutation of IME2. In vivo and in vitro assays suggested that a factor present in vegetative cells bind to the UASSPS4 element. We speculate that during sporulation this factor is modified to serve as an activator of the SPS4 gene or, alternatively, that it recruits an activator to the promoter. PMID- 7791801 TI - The decapentaplegic core promoter region plays an integral role in the spatial control of transcription. AB - The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor beta-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5'-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from -22 to +6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5'-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements. PMID- 7791802 TI - Molecular and genetic toxicology of 1,3-butadiene. AB - During the last 9 years, there have been many studies published concerning the mutagenic potential of butadiene in mammalian systems, including alterations at the molecular level. Butadiene has tested positive in several mouse in vivo and in vitro assays, but has generally tested negative in rat studies. Most of these studies are cytogenetic and include positive data in mice for chromosomal aberrations, micronucleus formation, and sister chromatid exchanges. Butadiene also induces mutations in lung, spleen, and bone marrow of transgenic mice. The positive bone marrow cytogenetic and transgenic data may be significant in view of the increased lymphohematopoietic malignancies observed in mice and probably in humans. In addition, butadiene causes mutations in the K-ras protooncogene and in the p53 tumor suppressor gene in mouse studies. Mutations in these genes are associated with oncogenesis in humans as well as in rodents. Also, positive mutagenicity data have been obtained in a pilot study of workers exposed to butadiene. Positive dominant lethal studies in rodents suggest that exposure to butadiene can result in germ cell mutation and heritable risk. These mutagenicity and molecular data suggest that butadiene is both a somatic and germ cell mutagen in mammals, possibly including humans. PMID- 7791800 TI - Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer. AB - Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID- 7791804 TI - Genotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). PMID- 7791805 TI - Stability of 1-nitropyrene and 1,6-dinitropyrene in environmental water samples and soil suspensions. AB - This study examined the stability of mutagenic 1-nitropyrene (1-NP) and (1,6 dinitropyrene (1,6-diNP) in environmental water samples and various soil suspensions containing 0.1% peptone and in water samples containing no peptone. The water samples or the soil suspensions were mixed with NPs and incubated at 30 degrees C. The stability of NPs was expressed as mutagenic activity remaining in the test solutions. The mutagenicity decreased rapidly when 1-NP or 1,6-diNP was incubated in unautoclaved test solutions containing 0.1% peptone but not when incubated in autoclaved test solutions. The mutagenicity in the soil suspensions, especially in the sludge, decreased faster than in the water samples. This was due to the large number of colony-forming units (CFU) in the soil suspensions. In the water samples containing 0.1% peptone, the mutagenicity of NPs in the polluted Tamiya River water decreased faster than in the unpolluted Yoshino River water. The rate of decrease was dependent on the number of CFU in the water samples. A large number of CFU decreased the mutagenicity more rapidly than did a small number of CFU in samples. The disappearance of mutagenicity was dependent on the initial concentrations of NPs. The periods required for a 50% decrease in the mutagenicity of 1-NP at the low concentration (0.2 microgram/ml) was shorter than that at the high concentration (3 micrograms/ml). 1-Aminopyrene was detected in the 1-NP test solution after incubation when it was analyzed by high-pressure liquid chromatography. In the water samples containing no peptone, the mutagenicity of 1-NP (0.2 microgram/ml) decreased gradually during 30 days of incubation. After incubation for 1540 days, the remaining mutagenicity of 1-NP in the water samples was almost the same as that in autoclaved water samples. On the other hand, the mutagenicity of 1,6-diNP (10 ng/ml) decreased and the remaining mutagenicity, except in the Yoshino River water, was less than 20% after 30 days of incubation and was completely lost during the 1540-day incubation. However, the mutagenicity of 1,6-diNP in autoclaved water samples was very stable and almost all mutagenicity, except in sea water, remained after 1540 days of incubation at 30 degrees C. These results suggest that the microflora in the environment plays an important role in the primary degradation and decontamination of relatively low concentrations of NPs. PMID- 7791803 TI - Potential genotoxicity of chronically elevated nitric oxide: a review. AB - Several human cancers are associated with chronic bacterial, viral and parasitic infections. Nitric oxide, which is a short-lived free radical produced by many types of cells for a number of important physiological functions, is elevated in these infections. Long-term exposure to elevated NO. in cells could have potential genotoxic effects on hosts. There are at least three mechanisms by which intracellular elevated NO. could exert genotoxic affects after reacting with O2. These include formation of carcinogenic N-nitroso compounds, direct deamination of DNA bases, and oxidation of DNA after formation of peroxynitrite and/or hydroxyl radicals. One or more of these mechanisms could, theoretically, explain why chronic infection increases the risk of certain cancers. PMID- 7791806 TI - Fish micronuclei for assessing genotoxicity in water. AB - Micronucleus assays with fish have been shown to be useful in vivo techniques for genotoxicity testing, and show potential for in situ monitoring of water quality. In this paper, we review the literature on the clastogenic effects of chemical and physical agents on fish cells, with emphasis on the induction of micronuclei in teleosts. Included in the review is a description of the mechanisms for formation of micronuclei in cells, and a summary of the various techniques that have been used for micronucleus analysis in fish. This review is directed to assisting laboratories in the development of fish genotoxicity assays for water quality monitoring. PMID- 7791808 TI - Mutagenicity and contents of polycyclic aromatic hydrocarbons in new high viscosity naphthenic oils and used and recycled mineral oils. AB - Mutagenic activity on the Ames test was evaluated in 15 samples of naphthenic high-viscosity mineral oils and 12 samples of used lubricants (recovered and pooled) and their recycled products. Bacterial mutagenesis was assayed using both the standard technique and Blackburn's modification. The contents of polycyclic aromatic hydrocarbons (PAH) was also evaluated, as polynuclear aromatic fraction (PAF) and total PAH, determined respectively with the semi-quantitative dimethylsulphoxide-refractive index method and the Grimmer method. Only four samples (three acid-treated naphthenic oils and one recycled fraction of a used oil) showed mutagenic activity higher than 6 revertants/mg of oil, considered by Blackburn and coworkers as indicating a potential carcinogenic risk for these compounds. Limited mutagenicity was found in all used and recycled oils, but also in samples of acid- or solvent-treated oils. No hydrogen-treated naphthenic oils turned out to have any mutagenic activity. PAF contents of oils were closely correlated with those of total PAH (n = 15, r = 0.83; n = 12, r = 0.91; p < 0.01 for both naphthenic and used/recycled oils respectively). No recycled oil had high PAF contents. Eleven samples had PAF contents higher than 3%, the arbitrary danger threshold suggested by the CONCAWE (1988). Of these 11 samples, the majority were acid-treated products, although there was one hydrogen-treated oil and one used and recycled oil. No mutagenic activity could be demonstrated in almost half the oils with PAF > 3%. In this study, the presence of mutagens was not correlated wither with PAF or with total or mutagenic PAH. The difficulty of predicting the mutagenicity of mineral oils is stressed. Most naphthenic and some recycled oils clearly have components which inhibit the metabolizing system in the bacterial mutagenesis test, with consequent possible false negative results. PMID- 7791807 TI - Mutagenic activity of the Ganges water with special reference to the pesticide pollution in the river between Kachla to Kannauj (U.P.), India. AB - Water samples from Ganga river were collected from 3 different locations viz. Kachla, Fatehgarh and Kannauj (U.P.). High performance liquid chromatography analysis of samples by liquid-liquid extraction procedure showed the presence of some pesticides like DDT, alpha-BHC, aldrin, dieldrin etc. DDT, alpha-BHC, DDD, aldrin and dieldrin were present at concentration ranges of 3.33-5.33 ppb, 1.73 3.01 ppb, 0.88-2.41 ppb, 1.17-2.81 ppb and 0.49-4.11 ppb, respectively. The organophosphorus pesticides like dimethoate and methyl parathion were also detected at the concentration levels of 0.41-0.56 ppb and 0.16-0.50 ppb, respectively. The organic substances in the test samples were extracted by XAD resin and liquid-liquid extraction procedures, and the extracts were assayed for mutagenic potential by the Ames Salmonella/microsome test. The test samples exhibited a remarkable degree of mutagenicity with TA98, TA100 and TA97a strains with the probable role of contaminating pesticides in the river water. PMID- 7791809 TI - Cytogenetic effects in the peripheral lymphocytes and kidney cells of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) orally on three consecutive days. AB - We reported previously that 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)- furanone (MX), a chlorine disinfection by-product in drinking water, induces sister chromatid exchanges (SCEs) in the peripheral lymphocytes of male and female rats after subchronic exposure. In the present study, we found that the peripheral lymphocytes of male rats exposed to MX (25-150 mg/kg) by gavage on three consecutive days showed a significant dose-related increase in chromosomal damage measured as micronuclei, in addition to SCEs. Moreover, MX produced a significant dose-related increase in SCEs in the kidney cells of the exposed rats. The magnitude of the genotoxic responses observed was relatively weak. The finding is, however, consistent with the known pharmacokinetic distribution of MX in the rat after oral dosing. PMID- 7791810 TI - The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens. AB - To assess the efficacy of the in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test as a short-term assay, 41 putative nongenotoxic (Ames negative) mouse hepatocarcinogens, as well as 31 noncarcinogens, were examined using male 8-week-old B6C3F1 mice and an in vitro [methyl-3]thymidine incorporation technique. Animals were exposed to the maximum tolerated dose (MTD) and 1/2 MTD of each chemical by gavage and after 24, 39 or 48 h, hepatocytes were prepared with a collagenase-perfusion technique. Assessment of the distribution of spontaneous RDS in a total of 337 control mice gave an average incidence of 0.15 +/- 0.08% within the range of 0 to 0.39% (mean +/- 3 x SE) with a 99.7% probability. Values of 0.4% or more for RDS incidences induced by test samples were therefore judged as indicating a positive response in our RDS test. Under the experimental conditions applied, 32 of 41 putative nongenotoxic hepatocarcinogens gave clear positive responses (positive sensitivity: 78%), and of 31 noncarcinogens 25 samples gave negative responses (negative specificity: 81%), thus giving an overall concordance for the RDS test with long-term findings of 79%. PMID- 7791811 TI - Prophylaxis of antioxidants against the genotoxicity of methyl mercuric chloride and maleic hydrazide in Allium micronucleus assay. AB - Antioxidants, namely cysteine, 2.46 x 10(-5) M; glutathione 9.75 x 10(-6), 9.75 x 10(-4) M; vitamin C, 10(-2) M; mannitol, 5 x 10(-2) M; potassium iodide, 5 x 10( 2) M and sodium selenite, 1.73 x 10(-6) M; were tested for their prophylactic activity against the genotoxicity of methylmercuric chloride, 1.26 x 10(-6) M and maleic hydrazide, 3 x 10(-4) M in Allium micronucleus assay. Antioxidants doses were administered simultaneously or prior to the genotoxic exposures. The results from the present experiments indicated that antioxidants conferred protection against the genotoxicity of both methyl mercuric chloride and maleic hydrazide. Furthermore, the protection of GSH against methyl mercuric chloride depending on the concentration persisted for 12 h. PMID- 7791812 TI - Genotoxicity of quercetin in the micronucleus assay in mouse bone marrow erythrocytes, human lymphocytes, V79 cell line and identification of kinetochore containing (CREST staining) micronuclei in human lymphocytes. AB - Quercetin, a mutagenic flavonoid widely distributed in edible plants, was studied for the induction of micronuclei (MN). We have carried out the MN assay in bone marrow polychromatic erythrocytes in mice, in cytokinesis-blocked human lymphocytes and in cytokinesis-blocked V79 cells. MN assay in vitro was performed in the presence and in the absence of S9. To further extend the study, an antikinetochore antibody (CREST staining) was used to distinguish MN containing whole chromosomes (kinetochore positive) from those containing acentric fragments (kinetochore negative). When tested in vivo quercetin failed to induce micronuclei, a result which is in agreement with other published reports. When tested in vitro in V79 cells quercetin clearly induces micronuclei in the absence of S9 and also in the presence of S9 for the highest dose used. When tested in vitro in human lymphocytes quercetin shows a significant induction of micronuclei in the absence and in the presence of S9. The presence of S9 compared to its absence is not significant for any of the systems used. Both in the presence and absence of S9, quercetin appears to behave as a clastogenic agent in human lymphocytes inducing a significant majority of kinetochore-negative MN. PMID- 7791813 TI - The genotoxicity profile of atorvastatin, a new drug in the treatment of hypercholesterolemia. AB - While HMG-CoA reductase inhibitors such as fluvastatin, lovastatin, pravastatin and simvastatin demonstrate lack of in vitro and in vivo mutagenicity and clastogenicity in bacterial and mammalian cells, long term rodent carcinogenicity studies resulted in an increased incidence in neoplasms at high doses. These effects may be attributable to an exaggeration of the desired biochemical effect of the drug and/or a tumor promoting effect. The genotoxicity of atorvastatin, a newly developed HMG-CoA reductase inhibitor, was evaluated in a variety of test systems. In bacterial mutagenicity tests, the E. coli tester strain WP2(uvrA) and S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 were exposed to concentrations of atorvastatin as high as 5000 micrograms/plate both in the absence (S9-) and presence (S9+) of metabolic activation. Atorvastatin was not mutagenic in either E. coli or S. typhimurium. Chinese hamster lung V79 cell cultures were exposed to atorvastatin at concentrations of 50-300 micrograms/ml (S9-) and 100-300 micrograms/ml (S9+) and structural chromosome aberrations were assessed. Mutation at the hgprt locus was assessed at concentrations of 100-300 micrograms/ml (S9-) and 150-275 micrograms/ml (S9+). Atorvastatin was neither mutagenic nor clastogenic in the absence or presence of S9. The lack of in vitro genotoxicity was corroborated in vivo in a mouse micronucleus study in which single oral doses of atorvastatin were administered to male and female CD-1 mice at 1, 2500, or 5000 mg/kg. No biologically significant increases in the frequency of micronucleated polychromatic erythrocytes in bone marrow at 24, 48, or 72 h postdosing were observed. Thus, atorvastatin, as with the other tested HMG-CoA reductase inhibitors, is not genotoxic. PMID- 7791814 TI - Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. AB - BACKGROUND: Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. METHODS: In a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day in two divided doses at 12-hour intervals) and methotrexate (at the maximal tolerated dose) with methotrexate and placebo in 148 patients with rheumatoid arthritis who had residual inflammation and disability despite partial but substantial responses to prior methotrexate treatment. The primary outcome measure was the change in the number of tender joints. RESULTS: The mean (+/- SD) dose of cyclosporine at the final treatment was 2.97 +/- 1.02 mg per kilogram per day. As compared with the placebo group, the patients in the treatment group had a net improvement in the tender-joint count of 25 percent, or 4.8 joints (95 percent confidence interval, 0.7 to 8.9; P = 0.02), and in the swollen-joint count of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P = 0.005); improvement in overall disease activity as assessed by the physician (19 percent, P < 0.001) and the patient (21 percent, P < 0.001); and improvement in joint pain (23 percent, P = 0.04) and in the degree of disability (26 percent, P < 0.001). The mean erythrocyte sedimentation rate increased by 4.2 mm per hour in the cyclosporine group and decreased by 4.8 mm per hour in the placebo group (P = 0.006). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P < 0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Seventeen patients in the cyclosporine group and 12 patients in the placebo group were withdrawn from the study; 2 patients in the cyclosporine group died, 1 from viral pneumonia and the other in a motor vehicle accident. Serum creatinine concentrations increased by a mean of 0.14 +/- 0.27 mg per deciliter (12 +/- 24 mmol per liter) in the cyclosporine group and by 0.05 +/- 0.19 mg per deciliter (4 +/- 17 mmol per liter) in the placebo group (P = 0.02). CONCLUSIONS: In a six-month study, patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with cyclosporine and methotrexate. Side effects were not substantially increased. Long-term follow-up of patients treated with this combination is needed. PMID- 7791815 TI - The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. AB - BACKGROUND: Oral glucocorticoids are widely used to treat patients with rheumatoid arthritis, but their effect on joint destruction, as assessed radiologically, is uncertain. METHODS: We conducted a randomized, double-blind trial comparing oral prednisolone (7.5 mg daily for two years) with placebo in 128 adults with active rheumatoid arthritis of less than two years' duration. Except for systemic corticosteroids, other treatments could be prescribed. The primary outcome variables were the progression of damage as seen on radiographs of the hand after one and two years, as measured by the Larsen index, and the appearance of erosions in hands that had no erosions at base line. The radiographs were viewed jointly by a radiologist and a rheumatologist who were unaware of the treatment assignment and the time point at which the films were obtained. RESULTS: The statistical analysis of radiologically detected changes was based on 106 patients for whom there were films obtained at base line and two years later. After two years, the Larsen scores increased by a mean of 0.72 unit in the prednisolone group, indicating very little change, and by 5.37 units in the placebo group, indicating substantial joint destruction (P = 0.004). Of the 212 hands of these patients, 147 (69.3 percent) had no erosions at the start of the study. At two years, 15 of the 68 such hands in the prednisolone group (22.1 percent) and 36 of the 79 such hands in the placebo group (45.6 percent) had acquired erosions (difference, 23.5 percentage points; 95 percent confidence interval, 5.9 to 40.7; P = 0.007). The patients in the prednisolone group had greater reductions than the patients in the placebo group in scores on an articular index and for pain and disability at 3 months; for pain at 6 months; and for disability at 6, 12, and 15 months (all P < 0.05). There was no difference between groups in standardized scores for the acute-phase response. The adverse events were typical of those encountered with antirheumatoid drugs. CONCLUSIONS: In patients with early, active rheumatoid arthritis, prednisolone (7.5 mg daily) given for two years in addition to other treatments substantially reduced the rate of radiologically detected progression of disease. PMID- 7791816 TI - Postoperative infections traced to contamination of an intravenous anesthetic, propofol. AB - BACKGROUND: Between June 1990 and February 1993, the Centers for Disease Control and Prevention conducted investigations at seven hospitals because of unusual outbreaks of bloodstream infections, surgical-site infections, and acute febrile episodes after surgical procedures. METHODS: We conducted case-control or cohort studies, or both, to identify risk factors. A case patient was defined as any patient who had an organism-specific infection or acute febrile episode after a surgical procedure during the study period in that hospital. The investigations also included reviews of procedures, cultures, and microbiologic studies of infecting, contaminating, and colonizing strains. RESULTS: Sixty-two case patients were identified, 49 (79 percent) of whom underwent surgery during an epidemic period. Postoperative complications were more frequent during the epidemic period than before it. Only exposure to propofol, a lipid-based anesthetic agent, was significantly associated with the postoperative complications at all seven hospitals. In six of the outbreaks, an etiologic agent (Staphylococcus aureus, Candida albicans, Moraxella osloensis, Enterobacter agglomerans, or Serratia marcescens) was identified, and the same strains were isolated from the case patients. Although cultures of unopened containers of propofol were negative, at two hospitals cultures of propofol from syringes currently in use were positive. At one hospital, the recovered organism was identical to the organism isolated from the case patients. Interviews with and observation of anesthesiology personnel documented a wide variety of lapses in aseptic techniques. CONCLUSIONS: With the increasing use of lipid-based medications, which support rapid bacterial growth at room temperature, strict aseptic techniques are essential during the handling of these agents to prevent extrinsic contamination and dangerous infectious complications. PMID- 7791817 TI - Attenuation of isoproterenol-mediated vasodilatation in blacks. AB - BACKGROUND: The mechanism of enhanced vascular reactivity in young blacks, which may play a part in the development of hypertension, has not been defined. To determine the contribution of blunted vasodilatation mediated by beta 2 adrenergic receptors to this phenomenon, we compared forearm blood-flow responses to isoproterenol in young black and white normotensive men. METHODS: We used venous-occlusion plethysmography to measure the responses of blood flow in the forearm to the intraarterial administration of isoproterenol (10 to 400 ng per minute) in 9 normotensive black men (mean [+/- SD] age, 31.3 +/- 8.0 years) and 13 normotensive white men (mean age, 32.9 +/- 5.6 years). Sympathetic activity in the forearm was measured simultaneously by isotope-dilution techniques. RESULTS: Base-line blood flow in the forearm was similar in blacks and whites, but the degree of vasodilatation in response to isoproterenol was markedly lower in blacks. Isoproterenol at an infusion rate of 400 ng per minute produced a 9-fold increase in blood flow in whites but only a 3.5-fold increase in blacks (P < 0.001). The base-line rate of norepinephrine spillover in the forearm was higher in blacks (2.0 +/- 1.3 ng per minute [11.8 +/- 7.7 nmol per minute]) than in whites (0.6 +/- 0.5 ng per minute [3.5 +/- 3.0 nmol per minute], P = 0.002), but there was no difference between the groups after isoproterenol stimulation. CONCLUSIONS: Forearm blood-flow responses to isoproterenol were markedly attenuated in normotensive blacks, indicating a blunting of vasodilatation mediated by beta 2-adrenergic receptors. Sympathetic activity in the forearm was greater in blacks than in whites, but isoproterenol-stimulated presynaptic beta 2 adrenergic responses (which facilitated norepinephrine release) did not differ significantly between blacks and whites. Our findings suggest that the mechanisms responsible for blunted vasodilatation in response to the administration of isoproterenol may contribute to enhanced vascular reactivity in blacks and may play a part in the pathogenesis of hypertension in blacks. PMID- 7791818 TI - Absence of an environmental effect on the recurrence of facial-cleft defects. AB - BACKGROUND: The rate of recurrence of a broad range of birth defects may decrease among women who change residence after the birth of their first infant. The aim of the present study was to determine the effect of changing residence on the recurrence of congenital facial-cleft defects. METHODS: We identified 4189 women who had infants with facial-cleft defects by linking a data base comprising the records of children with facial clefts born between 1952 and 1987 with the Central Person Registry in Denmark. Among the 4189 mothers, 1902 each had additional children after the first child with a facial-cleft defect. A total of 2692 younger siblings were identified. We compared the proportion of infants with facial-cleft defects among the younger siblings between mothers who had changed municipalities or sexual partners and those who had not. RESULTS: Changing the municipality of residence did not decrease the frequency with which facial-cleft defects recurred in younger siblings. Among the 907 infants of mothers who changed municipalities but not partners, 29 (3.2 percent) had facial-cleft defects, as compared with 48 (3.4 percent) of 1425 infants of mothers who changed neither municipality nor partner (relative risk, 0.9; 95 percent confidence interval, 0.6 to 1.5). However, a change of partner reduced the recurrence risk significantly. Among 236 infants of mothers who changed partners, 1 (0.4 percent) had a facial-cleft defect, as compared with 77 (3.3 percent) of 2350 infants of mothers who did not change partners (relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). CONCLUSIONS: Recurrence of facial-cleft defects is not linked to the residence of the mother, but having a different partner reduced a woman's risk of having a second child with this defect. PMID- 7791819 TI - Images in clinical medicine. Echinococcal cyst of the pericardium. PMID- 7791820 TI - Renal osteodystrophy. PMID- 7791821 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 22-1995. An 82-year-old woman with odynophagia and a large mediastinal mass. PMID- 7791822 TI - New perspectives on treating rheumatoid arthritis. PMID- 7791823 TI - Bacterial contamination of an anesthetic agent. PMID- 7791824 TI - Nicotine addiction in young people. PMID- 7791825 TI - Antibacterial treatment of gastric ulcers. PMID- 7791826 TI - Antibacterial treatment of gastric ulcers. PMID- 7791827 TI - Antibacterial treatment of gastric ulcers. PMID- 7791828 TI - Antibacterial treatment of gastric ulcers. PMID- 7791830 TI - Interleukin-2 as therapy for HIV disease. Dinitrochlorobenzene Study Group. PMID- 7791829 TI - Antibacterial treatment of gastric ulcers. PMID- 7791831 TI - Interleukin-2 as therapy for HIV disease. PMID- 7791832 TI - Molecular diagnosis of neoplasms. PMID- 7791833 TI - Molecular diagnosis of neoplasms. PMID- 7791834 TI - Relapsing lymphoma. PMID- 7791835 TI - Overdose of extended-release acetaminophen. PMID- 7791836 TI - A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. AB - BACKGROUND: Magnesium sulfate is used widely to prevent eclamptic seizures in pregnant women with hypertension, but few studies have compared the efficacy of magnesium sulfate with that of other drugs. Anticonvulsant prophylaxis with phenytoin for eclampsia has been recommended, but there are virtually no data to support its efficacy. Our objective was to compare magnesium sulfate with phenytoin in preventing seizures in hypertensive women during labor. METHODS: We randomly assigned women with hypertension who were admitted for delivery to receive either magnesium sulfate or phenytoin. The magnesium sulfate regimen consisted of a 10-g intramuscular loading dose followed by a maintenance dose of 5 g given intramuscularly every four hours. For women with severe preeclampsia, an additional 4-g loading dose was given intravenously. The phenytoin regimen included a 1000-mg loading dose infused over a period of 1 hour, followed by a 500-mg oral dose 10 hours later. With either regimen, anticonvulsant therapy was continued for 24 hours post partum. RESULTS: Ten of 1089 women randomly assigned to the phenytoin regimen had eclamptic convulsions, as compared with none of 1049 women randomly assigned to magnesium sulfate (P = 0.004). There were no significant differences in any risk factors for eclampsia between the two study groups. Maternal and infant outcomes were also similar in the two study groups. CONCLUSIONS: Magnesium sulfate is superior to phenytoin for the prevention of eclampsia in hypertensive pregnant women. These results validate the long practiced use of magnesium sulfate in the prevention of eclampsia. PMID- 7791838 TI - Outbreak of tuberculosis among regular patrons of a neighborhood bar. AB - BACKGROUND: Outbreaks of tuberculosis have been reported in prisons, nursing homes, urban homeless shelters, and other crowded settings. We report a nonresidential outbreak of tuberculosis that originated in a neighborhood bar. METHODS: A homeless patient with highly infectious pulmonary tuberculosis was a regular patron of a neighborhood bar during a long symptomatic interval before diagnosis. We investigated 97 other regular customers and employees of the bar through interviews, tuberculin skin testing, and chest roentgenography. We performed DNA fingerprinting on isolates from the index patient and 11 other patients. RESULTS: The index patient apparently infected 41 of 97 contacts (42 percent), resulting in 14 cases of active tuberculosis and 27 cases of infection but no disease (indicated by positive tuberculin skin tests). Four other cases of active tuberculosis occurred among regular customers of the bar who were missed by the contact investigation. There were also two secondary cases. Radiographic findings in active cases included upper-lobe disease in seven cases (three cavitary) and negative chest films at the time of diagnosis in four cases. All 12 culture isolates we tested had the same chromosomal-DNA restriction pattern. CONCLUSIONS: The spread of tuberculosis in a neighborhood bar can be a major public health problem. The high rate of infection and disease among the contacts was unexpected and was not due to coinfection with the human immunodeficiency virus. Possible explanations include heavy alcohol use among the contacts, high infectivity of the index case, or both. Sputum cultures must be performed in tuberculin-positive contacts who have symptoms, even if the chest films are normal. PMID- 7791839 TI - Images in clinical medicine. Giant colonic diverticulum. PMID- 7791840 TI - Tuberculosis in New York City--turning the tide. AB - BACKGROUND: From 1978 through 1992, the number of patients with tuberculosis in New York City nearly tripled, and the proportion of such patients who had drug resistant isolates of Mycobacterium tuberculosis more than doubled. METHODS: We reviewed, confirmed, and analyzed data obtained during the surveillance of patients with tuberculosis. RESULTS: From 1992 through 1994, there was a 21 percent decrease in reported cases of tuberculosis in New York City. An evaluation of the surveillance system revealed very few unreported cases. The number of cases decreased by more than 20 percent among blacks and Hispanics, persons with documented human immunodeficiency virus infection, homeless persons, and patients with multidrug-resistant tuberculosis; in all these groups, tuberculosis is likely to result from recent transmission. In contrast, the number of cases of tuberculosis increased among elderly and foreign-born persons, in whom the disease is likely to result from the reactivation of an infection acquired many years earlier. Enrollment in a program of directly observed therapy, in which health workers watch patients take their medications, increased from fewer than 100 patients to nearly 1300, with more than 32,000 patient-months of observation from 1992 through 1994. CONCLUSIONS: Epidemiologic patterns strongly suggest that the decrease in cases resulted from an interruption in the ongoing spread of M. tuberculosis infection, primarily because of better rates of completion of treatment and expanded use of directly observed therapy. Another contributing factor may have been efforts to reduce the spread of tuberculosis in institutional settings, such as hospitals, shelters, and jails. Expansion of measures to prevent and control tuberculosis and support of international control efforts are needed to ensure continued progress. PMID- 7791837 TI - A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. AB - BACKGROUND: Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose. METHODS: We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2). RESULTS: Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome. CONCLUSIONS: A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications. PMID- 7791841 TI - Calcium-ion-sensing cell-surface receptors. PMID- 7791842 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 23-1995. A 44-year-old woman with pulmonary infiltrates, respiratory failure, and pancytopenia. PMID- 7791843 TI - Magnesium for preeclampsia and eclampsia. PMID- 7791844 TI - Interval cytoreduction in ovarian cancer. PMID- 7791845 TI - Interval cytoreduction in ovarian cancer. PMID- 7791846 TI - Melanoma in children. PMID- 7791847 TI - Melanoma in children. PMID- 7791848 TI - More on skin cancer after the extravasation of doxorubicin. PMID- 7791849 TI - Patients with chronic diarrhea. PMID- 7791850 TI - Patients with chronic diarrhea. PMID- 7791852 TI - Treatment of psoriasis. PMID- 7791851 TI - Treatment of psoriasis. PMID- 7791853 TI - Recombinant tissue plasminogen activator for prosthetic mitral-valve thrombosis. PMID- 7791854 TI - Metaphors and health care reform. PMID- 7791855 TI - Metaphors and health care reform. PMID- 7791856 TI - Another truly presidential checkup. PMID- 7791857 TI - Honorary authorship. PMID- 7791858 TI - Masculinity at risk. PMID- 7791859 TI - Germany minister backs genome research. PMID- 7791861 TI - As US reviewer resigns over slur. PMID- 7791860 TI - Uproar greets new blood scandal indictment. PMID- 7791862 TI - UK fraud verdict prompts moves on ethics... PMID- 7791863 TI - Paradox of placebo effect. PMID- 7791864 TI - Applying a genetic cantilever. PMID- 7791865 TI - Drug design. Rules for the manipulation of polyketides. PMID- 7791866 TI - Planetary science. Sublime Solar System ices. PMID- 7791868 TI - Molecular pharmacology. Endothelin versatility. PMID- 7791867 TI - Reproductive biology. Another DDT connection. PMID- 7791869 TI - A human BRCA1 gene knockout. PMID- 7791870 TI - Mouse knockouts rule OK. PMID- 7791871 TI - Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic subunits. AB - Recent advances in understanding of bacterial aromatic polyketide biosynthesis allow the development of a set of design rules for the rational manipulation of chain synthesis, reduction of keto groups and early cyclization steps by genetic engineering. The concept of rational design is illustrated by the preparation of Streptomyces strains that produce two new polyketides by expression of combinations of appropriate enzymatic subunits from naturally occurring polyketide synthases. The potential for generating molecular diversity within this class of molecules by genetic engineering is enormous. PMID- 7791873 TI - Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. AB - The increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. The results suggest that abnormalities in male sex development induced by p,p'-DDE and related environmental chemicals may be mediated at the level of the androgen receptor. PMID- 7791872 TI - The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. AB - The X-ray crystal structure of the complex between the Ras-related protein Rap1A in the GTP-analogue (GppNHp) form and the Ras-binding domain (RBD) of the Ras effector molecule c-Raf1, a Ser/Thr-specific protein kinase, has been solved to a resolution of 2.2 A. It shows that RBD has the ubiquitin superfold and that the structure of Rap1A is very similar to that of Ras. The interaction between the two proteins is mediated by an apparent central antiparallel beta-sheet formed by strands B1-B2 from RBD and strands beta 2-beta 3 from Rap1A. Complex formation is mediated by main-chain and side-chain interactions of the so-called effector residues in the switch I region of Rap1A. PMID- 7791874 TI - Elevation of auditory thresholds by spontaneous cochlear oscillations. AB - The inner ear sometimes acts as a robust sound generator, continuously broadcasting sounds (spontaneous otoacoustic emissions) which can be intense enough to be heard by other individuals standing nearby. Paradoxically, most individuals are unaware of the sounds generated within their ears. Two hypotheses could explain this paradox: (1) the spontaneous emissions may not be transmitted to the central nervous system; or (2) the spontaneous emission produces a continuous, high rate of neural activity, which, like the natural pattern of spontaneous activity, is ignored by the central nervous system. Here we demonstrate that high-intensity spontaneous otoacoustic emission can vigorously activate auditory nerve fibres in mammals (Chinchilla laniger). This 'internal biological noise' creates a 'line busy' signal that significantly degrades a neuron's ability to respond to sound and results in a hearing loss completely different from that caused by damage to sensory cells. PMID- 7791875 TI - Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila. AB - Much work on the signal transduction mechanisms underlying neurotransmission has been directed towards studying the roles of the cyclic AMP and phosphoinositide pathways. Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing G alpha and G beta gamma subunits to disengage. The free G alpha then modulates the activity of adenylyl cyclase and phospholipase C. It has been suggested that the G beta gamma complex which is activated through muscarinic or neuropeptide receptors can stimulate mitogen activated protein kinase (MAPK) via activation of the small guanine-nucleotide binding protein Ras. Sequential activation of the intermediates in the Ras/Raf serine-threonine protein kinase/MAPK kinase/MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals. Here we show, by analysis of Drosophila mutants, that synaptic current and modulation of K+ current, triggered by a pituitary adenylyl cyclase-activating polypeptide-like neuropeptide, are mediated by coactivation of the Ras/Raf and Rutabaga-adenylyl cyclase pathways. Thus the Ras/Raf pathway also appears to be essential for G protein-coupled neurotransmission. PMID- 7791876 TI - Preferential addition of newly synthesized membrane protein at axonal growth cones. AB - The addition of plasma membrane proteins to a growing axon could occur by preferential insertion at the tip (the growth cone), by uniform insertion along the axon, or by insertion at the cell body and bulk flow along the axon. To differentiate between these possibilities we used a defective herpesvirus vector to express an exogenous protein, the lymphocyte transmembrane protein CD8 alpha, in cultured rat hippocampal neurons. The newly synthesized protein first appeared on the axonal surface almost exclusively at the growth cone. Preferential addition at the growth cone was also observed in minor processes (immature dendrites), but not in mature dendrites. Over several hours, CD8 alpha reached a uniform distribution over the entire neuronal surface, presumably by diffusion within the membrane and possibly endocytic recycling. As well as providing materials for axonal growth, the selective addition of membrane vesicles at the growth cone may contribute to the polarized distribution of axonal surface molecules. PMID- 7791877 TI - Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins. AB - Synaptotagmins (Syts) are brain-specific Ca2+/phospholipid-binding proteins. In hippocampal synapses, Syt I is essential for fast Ca(2+)-dependent synaptic vesicle exocytosis but not for Ca(2+)-independent exocytosis. In vertebrates and invertebrates, Syt may therefore participate in Ca(2+)-dependent synaptic membrane fusion, either by serving as the Ca2+ sensor in the last step of fast Ca(2+)-triggered neurotransmitter release, or by collaborating with an additional Ca2+ sensor. While Syt I binds Ca2+ (refs 10, 11), its phospholipid binding is triggered at lower calcium concentrations (EC50 = 3-6 microM) than those required for exocytosis. Furthermore, Syts bind clathrin-AP2 with high affinity, indicating that they may play a general role in endocytosis rather than being confined to a specialized function in regulated exocytosis. Here we resolve this apparent contradiction by describing four Syts, three of which (Syt VI, VII and VIII) are widely expressed in non-neural tissues. All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins. The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids with a similar Ca(2+)-concentration dependence (EC50 = 3-6 microM). The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs from that of Syt III and VII (< 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791878 TI - An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. AB - Excitatory amino-acid transporters (EAATs) in the central nervous system maintain extracellular glutamate concentrations below excitotoxic levels and may limit the activation of glutamate receptors. Here we report the cloning of a novel human aspartate/glutamate transporter, EAAT4, which is expressed predominantly in the cerebellum. The transport activity encoded by EAAT4 has high apparent affinity for L-aspartate and L-glutamate, and has a pharmacological profile consistent with previously described cerebellar transport activities. In Xenopus oocytes expressing EAAT4, L-aspartate and L-glutamate elicited a current predominantly carried by chloride ions. This chloride conductance was not blocked by components that block endogenous oocyte chloride channels. Thus EAAT4 combines the re-uptake of neurotransmitter with a mechanism for increasing chloride permeability, both of which could regulate excitatory neurotransmission. PMID- 7791879 TI - Antigenic oscillations and shifting immunodominance in HIV-1 infections. AB - A typical protein antigen contains several epitopes that can be recognized by cytotoxic T lymphocytes (CTL), but in a characteristic antiviral immune response in vivo, CTL recognize only a small number of these potential epitopes, sometimes only one, this phenomenon is known as immunodominance. Antigenic variation within CTL epitopes has been demonstrated for the human immunodeficiency virus HIV-1 (ref. 11) and other viruses and such 'antigenic escape' may be responsible for viral persistence. Here we develop a new mathematical model that deals with the interaction between CTL and multiple epitopes of a genetically variable pathogen, and show that the nonlinear competition among CTL responses against different epitopes can explain immunodominance. This model suggests that an antigenically homogeneous pathogen population tends to induce a dominant response against a single epitope, whereas a heterogeneous pathogen population can stimulate complicated fluctuating responses against multiple epitopes. Antigenic variation in the immunodominant epitope can shift responses to weaker epitopes and thereby reduce immunological control of the pathogen population. These ideas are consistent with detailed longitudinal studies of CTL responses in HIV-1 infected patients. For vaccine design, the model suggests that the major response should be directed against conserved epitopes even if they are subdominant. PMID- 7791880 TI - A DNA metalloenzyme with DNA ligase activity. AB - Single-stranded DNA can fold into well-defined sequence-dependent tertiary structures that specifically bind a variety of target molecules, raising the possibility that some folded single-stranded DNAs might exhibit catalytic activities similar to those of ribozymes and protein enzymes. Derivatives of the hammerhead ribozyme that contain a majority of deoxyribonucleotides retain the ability to cleave RNA, and a 'deoxyribozyme' was generated by leaving all essential ribonucleotides of the hammerhead on the RNA 'substrate'. Recently in vitro selection has been used to isolate a DNA sequence that shows Pb(2+) dependent RNA-cleaving activity. Here we report the isolation by in vitro selection of a small single-stranded DNA that is a Zn2+/Cu(2+)-dependent metalloenzyme. The enzyme catalyses the formation of a new phosphodiester bond by the condensation of the 5'-hydroxyl of one oligodeoxynucleotide and a 3' phosphorimidazolide on another oligodeoxynucleotide, and shows multiple turnover ligation. PMID- 7791882 TI - Life sciences gain favour in patents. PMID- 7791881 TI - How to police fraud. PMID- 7791883 TI - UK panel warns of crisis in clinical research careers. PMID- 7791886 TI - Citation analysis. PMID- 7791885 TI - ET search project in struggle for survival. PMID- 7791884 TI - NASA scientists rapped over experiments with animals. PMID- 7791887 TI - Mannerly research. PMID- 7791888 TI - Preserving embryos. PMID- 7791889 TI - Elastic properties of DNA revealed. PMID- 7791890 TI - Prion diseases. Yielding under the strain. PMID- 7791891 TI - Footnote on limb evolution. PMID- 7791892 TI - Muscle contraction. Crossbridge tilting confirmed. PMID- 7791893 TI - Intracellular calcium. Replenishing the stores. PMID- 7791894 TI - Neurobiology. New visions of the cortex. PMID- 7791895 TI - HIV clearance in an infant? PMID- 7791896 TI - Advantage of diabetes? PMID- 7791897 TI - The synaptic vesicle cycle: a cascade of protein-protein interactions. AB - The synaptic vesicle cycle at the nerve terminal consists of vesicle exocytosis with neurotransmitter release, endocytosis of empty vesicles, and regeneration of fresh vesicles. Of all cellular transport pathways, the synaptic vesicle cycle is the fastest and the most tightly regulated. A convergence of results now allows formulation of molecular models for key steps of the cycle. These developments may form the basis for a mechanistic understanding of higher neural function. PMID- 7791898 TI - Polarization of both major body axes in Drosophila by gurken-torpedo signalling. AB - Anterior-posterior polarity in Drosophila arises from the movement of the oocyte to the posterior of the egg chamber, and the subsequent acquisition of posterior fate by the adjacent somatic follicle cells. We demonstrate that gurken is necessary in the oocyte and torpedo/DER in the follicle cells for the induction of posterior fate. As the gurken-torpedo/DER pathway also establishes dorsoventral polarity later in oogenesis, Drosophila uses the same germline to soma signalling pathway to determine both embryonic axes. PMID- 7791899 TI - Speciation driven by natural selection in Drosophila. AB - Reinforcement is the process by which natural selection strengthens sexual isolation between incipient species, reducing the frequency of maladaptive hybridization and hence completing reproductive isolation. Although this model of speciation was once widely accepted, its plausibility and experimental support have been recently attacked. Here we provide an example of speciation by reinforcement, in the North American fruitfly Drosophila pseudoobscura. The results suggest that females of D. pseudoobscura evolved increased sexual isolation from their sibling species, D. persimilis, by natural selection against maladaptive hybridization. PMID- 7791900 TI - Hox gene expression in teleost fins and the origin of vertebrate digits. AB - Hox genes are essential for growth and patterning of the tetrapod limb skeleton. Mice mutant for the Hoxd-13 gene have an important delay in morphogenesis owing to reduced proliferation. Based on the appearance of atavisms in such mice, we suggested that modifications of Hox gene regulation may have been a source of morphological variation during the evolution of tetrapod limbs. Pectoral and pelvic fins are homologous to fore- and hindlimbs, respectively. To compare the relative importance of Hox genes during fin versus limb morphogenesis, we cloned zebrafish (Danio rerio) HoxD and HoxA complex genes and analysed their expression during fin development. The results suggest a scheme for the fin-limb transition in which the distal autopods (digits) are neomorphic structures produced by unequal proliferation of the posterior part of an ancestral appendix. PMID- 7791901 TI - Dendritic spines as basic functional units of neuronal integration. AB - Most excitatory synaptic connections occur on dendritic spines. Calcium imaging experiments have suggested that spines constitute individual calcium compartments, but recent results have challenged this idea. Using two-photon microscopy to image fluorescence with high resolution in strongly scattering tissue, we measured calcium dynamics in spines from CA1 pyramidal neurons in slices of rat hippocampus. Subthreshold synaptic stimulation and spontaneous synaptic events produced calcium accumulations that were localized to isolated spines, showed stochastic failure, and were abolished by postsynaptic blockers. Single somatic spikes induced fast-peaking calcium accumulation in spines throughout the cell. Pairing of spikes with synaptic stimulation was frequently cooperative, that is, it resulted in supralinear calcium accumulations. We conclude: (1) calcium channels exist in spine heads; (2) action potentials invade the spines; (3) spines are individual calcium compartments; and (4) spines can individually detect the temporal coincidence of pre- and postsynaptic activity, and thus serve as basic functional units of neuronal integration. PMID- 7791902 TI - Tilting of the light-chain region of myosin during step length changes and active force generation in skeletal muscle. AB - Force generation and relative sliding between the myosin and actin filaments in muscle are thought to be caused by tilting of the head region of the myosin crossbridges between the filaments. Structural and spectroscopic experiments have demonstrated segmental flexibility of myosin in muscle, but have not shown a direct linkage between tilting of the myosin heads and either force generation or filament sliding. Here we use fluorescence polarization to detect changes in the orientation of the light-chain region of the head, the part most likely to tilt, and synchronized head movements by imposing rapid length steps. We found that the light-chain region of the myosin head tilts both during the imposed filament sliding and during the subsequent quick force recovery that is thought to signal the elementary force-generating event. PMID- 7791903 TI - Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. AB - The MDM2 proto-oncogene is found amplified in a variety of tumours. The oncogenic capacity of the MDM2 protein is attributed to its ability to bind the p53 tumour suppressor protein and mask its transcriptional activation potential. Here we show that MDM2 makes a functional contact with two cooperating transcription factors, E2F1 and DP1 (refs 4,5), which are involved in S-phase progression. MDM2 contacts the activation domain of E2F1 using residues conserved in the activation domain of p53. However, in contrast to its repression of p53 activity, MDM2 stimulates the activation capacity of E2F1/DP1. These results indicate that MDM2 not only releases a proliferative block by silencing the tumour suppressor p53, it also positively augments proliferation by stimulating the S-phase inducing transcription factors E2F1/DP1. PMID- 7791904 TI - Interaction between the retinoblastoma protein and the oncoprotein MDM2. AB - Inactivation of tumour-suppressor genes leads to deregulated cell proliferation and is a key factor in human tumorigenesis. Both p53 and retinoblastoma genes are frequently mutated in human cancers, and the simultaneous inactivation of RB and p53 is frequently observed in a variety of naturally occurring human tumours. Furthermore, three distinct DNA tumour virus groups--papovaviruses, adenoviruses and human papillomaviruses--transform cells by targeting and inactivating certain functions of both the p53 and retinoblastoma proteins. The cellular oncoprotein, Mdm2, binds to and downmodulates p53 function; its human homologue, MDM2, is amplified in certain human tumours, including sarcomas and gliomas. Overproduction of Mdm2 is both tumorigenic and capable of immortalizing primary rat embryo fibroblasts. Here we show that MDM2 interacts physically and functionally with pRB and, as with p53, inhibits pRB growth regulatory function. Therefore, both pRB and p53 can be subjected to negative regulation by the product of a single cellular protooncogene. PMID- 7791905 TI - Non-genetic propagation of strain-specific properties of scrapie prion protein. AB - The infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc). One unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in PrPSc structure, rather than mutations in an agent specific nucleic acid. Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME), a scrapie-like disease originating in mink. Although HY and DY PrPSc are both post-translationally derived from the precursor prion protein (PrPC) they are cleaved at different amino-terminal sites by proteinase K (ref. 8). Here we investigate whether this strain-specific property of PrPSc is transmitted to PrPC during formation of new PrPSc. PrPSc from the HY and DY TME strains converted the protease-sensitive PrPC into two distinct sets of protease resistant PrP products in a cell-free system. These data provide evidence that self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains. PMID- 7791906 TI - Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. AB - Penicillin antibiotics are all produced from fermentation-derived penicillins because their chemical synthesis is not commercially viable. The key step in penicillin biosynthesis, in which both the beta-lactam and thiazolidine rings of the nucleus are created, is mediated by isopenicillin N synthase (IPNS), which binds ferrous iron and uses dioxygen as a cosubstrate. In a unique enzymatic step, with no chemical precedent, IPNS catalyses the transfer of four hydrogen atoms from its tripeptide substrate to dioxygen forming, in a single reaction, the complete bicyclic nucleus of the penicillins. We now report the structure of IPNS complexed with manganese, which reveals the active site is unusually buried within a 'jelly-roll' motif and lined by hydrophobic residues, and suggest how this structure permits the process of penicillin formation. Sequence analyses indicate IPNS, 1-aminocyclopropane-1-carboxylic acid oxidase and many of the 2 oxo-acid-dependent oxygenases contain a conserved jelly-roll motif, forming a new structural family of enzymes. PMID- 7791907 TI - [Stereotactic radiosurgery]. PMID- 7791908 TI - [Application of leukocyte-poor blood products. Work Group Blood Group Serology from the Medical Advisory Commission of the College for Blood Transfusion]. PMID- 7791909 TI - [5 patients with Takayasu's disease in The Netherlands]. AB - OBJECTIVE: To describe the patients with Takayasu's disease in the University Hospital Nijmegen, and to compare these patients with literature. DESIGN: Retrospective, descriptive. SETTING: University Hospital Nijmegen. METHODS: All patients with Takayasu's disease in the period of 1980-1993 were traced via medical registration codes. These patients are described and compared with the literature. RESULTS: Five patients with Takayasu's disease were found, 3 women and 2 men, 4 Dutch and I Turkish female. The diagnosis in all patients was made before the age of 21 and confirmed by angiography. Four of the 5 patients presented initially with general complaints, and, except for patient A, all had a pulse or blood pressure difference (left-right) to the disadvantage of the left arm. Occlusion of the left subclavian artery occurred finally in all cases. Four patients had associated diseases as described in the literature. Four of the 5 showed no progression on prednisone therapy. Until now no patient has died, with a mean follow-up of 10 years. CONCLUSIONS: Takayasu's disease is rare in the Netherlands. First symptoms are general fatigue and a pulse/blood pressure difference. Early detection by medical history, physical examination and angiography appears beneficial, because early treatment may have a favourable effect on prognosis. PMID- 7791910 TI - [Consensus noninvasive diagnosis of peripheral arterial vascular diseases. Central Guidance Organization for Peer Review]. AB - The outcome is described of a 1993 consensus meeting regarding the role and value of functional non-invasive vascular investigations in the assessment of severity and localization of arterial obstructions and in the selection of a therapeutic strategy in patients with arterial obstructive disease of the lower extremities. Since symptoms and clinical investigation alone are unreliable in assessing the severity of peripheral arterial disease, complementary functional vascular examinations are needed. Measurement of the systolic blood pressures at ankle level by means of a sphygmomanometric method and a Doppler flowmeter allows reliable determination of the presence or absence of haemodynamically significant arterial obstructions. In the case of minor obstructions the sensitivity of ankle pressure measurements can be increased by examination during a period of hyperaemia, preferably induced by a treadmill walking test. In the case of unreliable ankle pressure measurements due to non-compressible arteries determination of the toe blood pressure is indicated. Segmental blood pressure measurements as well as Doppler analysis of the blood flow at various levels of the leg were not considered reliable enough for the localization of arterial obstructions, unless the obstructive disease is restricted to one single arterial segment. Accurate non-invasive localization of arterial obstructions and the determination of their haemodynamic severity are only possible by means of a combined echo-Doppler (duplex) examination of the arteries. Duplex examination can also be helpful in choosing between surgery and percutaneous transluminal angioplasty of localised stenoses and short occlusions. PMID- 7791911 TI - [How sick is the neonatal intensive care patient? Limited prognostic significance of the Neonatal Therapeutic Intervention Scoring System for mortality and for psychomotor development in the first year of life]. AB - OBJECTIVE: To study the Neonatal therapeutic intervention scoring system (NTISS score) as a prognostic indicator for mortality and psychomotor development in newborns admitted to an intensive care unit. DESIGN: Retrospective. SETTING: Neonatal intensive care unit, Sophia Hospital, Zwolle, the Netherlands. METHOD: The medical files of all neonates (n = 152) admitted for intensive care in 1991 were studied. The NTISS scores at admission were compared of infants with birthweights < 1500 g and > or = 1500 g and in these groups of infants who died and infants who survived and of infants with normal and with abnormal psychomotor development in the first year of life regardless of their birthweight (data of 110 children were available from outpatient clinic control or reports from paediatricians). RESULTS: 22 infants died. There was no significant correlation between NTISS score and birthweight or gestational age (r = -0.07 and -0.03 respectively). In the group of very low birthweight infants, the NTISS score was significantly higher of the infants who died (25.9; SD: 4.3) than of those who survived (15.9; 5.0). The NTISS score did not differ between infants with normal and with abnormal psychomotor development. CONCLUSION: The NTISS score at admission only correlates with mortality in infants with birthweights < 1500 g. There is no correlation with mortality in infants with birthweights > or = 1500 g, with gestational age or with psychomotor development in the first year of life. PMID- 7791912 TI - [Femoral neck fractures in bicyclists due to clipless pedals]. AB - Femoral neck fractures in healthy young adults caused by a relatively low-energy trauma are uncommon. The cases are presented of four cyclists, men of 37, 42 (n = 2) and 43 years old, with a femoral neck fracture, in which so called clipless pedals played an important part. The shoes of the cyclist are affixed to these pedals, and the patients had been unable to remove their feet quickly when they fell. They were treated by osteosynthesis using screws, but one of them developed intra-articular infection which eventually necessitated implantation of a total hip prosthesis. PMID- 7791913 TI - [Unrecognized neurological symptoms following a visit to the Caribbean Region: ciguatoxin poisoning]. PMID- 7791914 TI - [Variation in management and quality of medical decision making; discussion of a conference of the National Forum Medical Decision Making]. PMID- 7791915 TI - [Belt and suspenders. Medical jargon in The Netherlands and Flanders]. PMID- 7791916 TI - [Anal blood loss during pregnancy, a symptom which should be taken seriously]. PMID- 7791917 TI - [Anal blood loss during pregnancy, a symptom which should be taken seriously]. PMID- 7791918 TI - [Antifibrinolytic therapy]. PMID- 7791919 TI - [The dilemma of 'the final laparotomy']. PMID- 7791920 TI - [Promotion of rapid and oriented referral of patients with possible heart infarct by ECG at home]. PMID- 7791922 TI - [Local treatment of dermatoses in pregnancy]. PMID- 7791921 TI - [Immunopathology of Sjogren syndrome]. PMID- 7791923 TI - [The quality of referral letters to the gynecologist compared with the standard of the Dutch Family Physicians Society]. AB - The quality of referral letters to the gynaecologist compared with the standard of the Dutch Association of General Practitioners. OBJECTIVE. To assess the quality of referral letters of general practitioners (GP) used to refer new patients to a gynaecologic outpatient clinic. DESIGN. Prospective study. SETTING. Gynaecologic outpatients' clinic, Medical Centre Alkmaar, the Netherlands. METHOD. The actual quality of referral letters was compared with ideal quality, as defined by the Dutch Association of General Practitioners (NHG) in 1989. RESULTS. Fifty-three (14%) of the 373 new patients did not have a referral letter: 23 women (6%) consulted the gynaecologist without having consulted their GP first. Of the 320 referral letters 63% conformed to the NHG criteria and 27% contained a specific question to the specialist. One hundred and fifty-two letters (47%) were handwritten, of which 32 (10% of the total) were hardly legible. A good to excellent letter had a length of slightly more than 6 to 8 lines (A4 size). CONCLUSION. Of all 320 letters analysed 15% was qualified as 'excellent', 48% as 'reasonable/good', 25% as 'brief/just adequate' and 12% as 'inadequate/insufficient'. PMID- 7791924 TI - [The ideal physician: medical students' image of the profession]. AB - OBJECTIVE: To investigate the view medical students have of the medical profession. DESIGN: Cross sectional study of year cohorts, Utrecht. METHOD: The attitudes of 445 medical students towards the 'ideal physician' were studied. It is often assumed that medical students' attitudes change to a less care-oriented direction as they proceed in their education. It is also assumed that female students' attitudes are more care-oriented than male students' attitudes. Traits of the ideal physician were described in a scale of 18 care-versus cure oriented items. Validity and reliability of the measuring instrument were sufficient. The scores of pre-clinical and clinical, male and female students were obtained. RESULTS: Contrary to expectation, ideals of clinical students. In were more care oriented than ideals of beginning students. In general, students' ideals were neutral to slightly care-oriented. As was expected, female students' ideals were more care-oriented than male students' ideals. CONCLUSION: Medical students did not lose their slightly care-oriented ideals as they progressed. Female students held more care-oriented attitudes than their male colleagues. PMID- 7791925 TI - [Endovascular stent in the treatment of residual pulmonary stenosis in patients operated on for congenital heart defects; initial results]. AB - OBJECTIVE: Evaluation of the preliminary results of stent implantation as a new technique of intervention cardiology to treat (residual) stenosis of pulmonary arteries in congenital heart disease. DESIGN: Descriptive. SETTING: Children's Heart Centre, University Hospital Nijmegen, the Netherlands. METHODS: Data about physical condition, heart catheterization/angiography and lung perfusion scan were collected. Special attention was paid to the lung perfusion scan as a potential parameter of evaluation. RESULTS: The physical condition was not a useful parameter to judge the result of the pulmonary intravascular stenting, due to a simultaneously present important pulmonary valve insufficiency in most cases. Angiography showed a good result immediately after the procedure in all cases, except in one with kinking of the stent. The increase of lung perfusion could be confirmed by lung scintigraphy in most cases. The relative perfusion of the affected lung increased from 22.7% (SD: 10.8) to 38.6% (12.3) (p < or = 0.001). CONCLUSION: Percutaneous implantation of endovascular stents in pulmonary artery branch stenosis is a welcome alternative to (reconstructive) cardiac surgery. Objective quantification of this stenting by lung perfusion scintigraphy, a technique without patient discomfort, is possible. PMID- 7791927 TI - [Coalition agreement 1994: policy breach or continuity in the field of health care?]. PMID- 7791926 TI - [The legacy of Rudolph Hendrik Saltet]. PMID- 7791928 TI - [Travel experiences in Central and Eastern Europe: Hungary, Poland and former Czechoslovakia]. PMID- 7791930 TI - [Liver transplantation; indications, contraindications and the right time for referral]. PMID- 7791931 TI - [Heart surgery and interventional cardiology for adults; Health Council recommendations]. AB - In the scientifically solidly based report 'Heart surgery and intervention cardiology for adults' the Dutch Health Council presents its advice relating to the expected developments in the area of invasive treatment of coronary diseases, mainly coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). The Council advocates combined cardiological surgical discussions about indications for CABG and PTCA and central registration of data. Minimum requirements to guarantee quality of a treatment centre are the presence of 5 heart surgeons and 5 intervention cardiologists each performing 150 and 100 interventions a year, respectively. It is, according to the Council, not possible to determine the maximum size of a treatment centre scientifically. Concerning the waiting lists, the Council recommends a maximal waiting time of 2 3 months. It is interesting to follow the developments as on the one hand the Government wants to deregulate, whereas on the other it advocates a centralized approach. PMID- 7791929 TI - [Small bowel transplantation and short bowel syndrome]. PMID- 7791932 TI - [Pain and pain measurement in children]. PMID- 7791933 TI - [Duplex ultrasonography study in the diagnosis of cerebral, abdominal and peripheral artery stenoses]. PMID- 7791934 TI - [Indications for an increase in lung disease caused by Mycobacterium kansasii in the former Limburg mining area?]. AB - OBJECTIVE: To establish the occurrence of lung disease caused by Mycobacterium kansasii in order to determine whether the incidence has increased since 1991. DESIGN: Descriptive and retrospective. SETTING: The former coal-mining region (Limburg) of the Netherlands. METHOD: The occurrence of lung disease caused by M. kansasii and other non tuberculous mycobacteria (NTM) in the Netherlands and in the former coal-mining region in particular, was inferred from reports of tuberculosis of the national and local Public Health Authorities and of the Regional Public Health Laboratory. RESULTS: Between 1991 and 1993 in the former coal-mining region of the Netherlands 43 cases of tuberculosis were reported, of which 12 afterwards proved to be caused by M. kansasii, i.e. more than were diagnosed in the ten preceding years. An epidemiological relationship between these patients could be neither established nor disproved. CONCLUSION: The incidence of NTM diseases may be increasing with falling prevalence rates of tuberculosis infection. As lung disease caused by M. kansasii is not transmissible from man to man and its treatment is different from that of lung tuberculosis, it is essential to be able to differentiate between these diagnoses quickly by using rapid modern microbiological identification methods, and to determine the epidemiological links. PMID- 7791935 TI - [Consensus depression in adults. Dutch Association for Psychiatry]. AB - Depression is a frequent and treatable disorder, but it is insufficiently recognized. A generally used classification system is lacking. In a consensus meeting the following terms were defined: a normal feeling of depression, depression as a symptom and depression as an illness. The use of the term 'masked depression' was advised against. The undertreatment mentioned is caused by the following factors: presentation of physical symptoms by depressive patients, unfamiliarity of patients with depressive disorders and difficulties of patients and GPs in labelling depression as mental. Depressive disorders have various causes. For scoring the severity of depression the Bech version of the Hamilton Depression Rating Scale is preferred. There is no valid laboratory test for diagnosing depression. Laboratory tests are recommended to exclude physical disorders, for choosing an antidepressant and for the follow-up of drug treatment. Cognitive Behavioural Therapy and Interpersonal Therapy are preferred psychotherapeutic methods because of their scientifically proved efficacy. Women suffer from depression twice as frequently as men, which is due to social factors rather than to genetic or hormonal factors. Therefore hormonal therapy is not indicated, a more equal doctor-patient relationship is. Patients with a depressive disorder may consider suicide; this should regularly be discussed with them. PMID- 7791936 TI - [Improved diabetes control through strict observance of the standard 'Type II Diabetes Mellitus' from the Dutch College of Family Physicians]. AB - OBJECTIVE: Comparison of diabetes regulation by strict or less strict observance of the relevant standard protocol of the Netherlands College of General Practitioners (NHG standard). SETTING: Two general practices in the region 'Nieuwe Waterweg Noord', near Rotterdam, the Netherlands. DESIGN: Cross-sectional comparative descriptive study. METHOD: Type II diabetic patients from two general practices were investigated for diabetic symptoms, type of medication, metabolic abnormalities and (risk factors for) complications in relation to their HbA1c as a measure of mean blood glucose regulation. One GP strictly observed the NHG standard as a protocol, the other GP used it as a guideline. RESULTS: Metabolic control was significantly better in the 'strictly observing' general practice than in the 'guideline' practice: HbA1c 7.3% (SD: 1.7) versus 8.1% (1.5) (p < 0.01). Systolic blood pressure was also significantly lower in the 'strict' practice: 141 mmHg (23) versus 155 mmHg (21) (p < 0.01), but mean age was lower and mean duration of diabetes was significantly shorter. The prevalence of macrovascular complications, diabetic retinopathy and nephropathy did not differ significantly in these practices; symptoms of polyneuropathy, however, were found more often in the patients of the 'strict' practice (41% versus 20%; p < 0.05). CONCLUSION: Good metabolic control in patients with type II diabetes mellitus is made possible by strict application of the NHG standard for general practitioners. PMID- 7791937 TI - [Medical program Memisa in Mugunga Camp, Goma, Zaire, August-October 1994]. PMID- 7791938 TI - [Treatment of hyperthyroidism and indications for radioactive iodine]. PMID- 7791939 TI - [Prion diseases: a new class of neurodegenerative disorders]. PMID- 7791940 TI - [A pre-auricular swelling: not always parotitis!]. PMID- 7791941 TI - Thoughts and observations regarding dementia evaluation. PMID- 7791943 TI - Cocaine: how dangerous is it during pregnancy? AB - The risk of prematurity, stillbirth, small for gestational age, and central nervous system damage are clearly a consequence of maternal cocaine use during pregnancy. There is also the risk of concommitent use of alcohol which may cause long term developmental problems. Therefore cocaine should be avoided in pregnancy, but the good news is that if the child survives, the longterm outcome may be very favorable. The cocaine exposed child given proper parenting and educational support may well develop normally with a bright future. It is important not to be too pessimistic about the term infant exposed to cocaine since it may lead to a "self-fulfilling prophecy". Supporting the cocaine exposed child and their family is an important task for all health professionals who deal with children. PMID- 7791944 TI - Acetabular fractures. AB - Acetabular fractures are not uncommon injuries of the pelvis. They are most frequently associated with high energy trauma such as that seen in a motor vehicle accident. Management of patients with acetabular fractures includes careful attention to ATLS (advanced Trauma Life Support) protocols and delayed operative treatment of the acetabular fractures. Diagnostic evaluation with plain radiography and CT is used to plan the treatment approach. Treatment includes not only the recognition of the fracture but avoidance of early and late complications. Emergent treatment includes closed reduction of associated hip dislocations followed by skeletal traction. Delayed reconstruction at four days after the injury decreases intraoperative blood loss by allowing retroperitoneal hemorrhage to subside. Final outcome after acetabular trauma depends not only on the reconstruction of the fracture, but the avoidance of complications. Acetabular fractures are becoming an increasingly common orthopedic injury. Fractures of the acetabulum (or hip socket) are most commonly seen after motor vehicle accidents. Young patients (18 to 30 years old) are typically affected. A frequent mechanism of injury is a direct blow to the anterior aspect of the knee with the hip flexed such as a dashboard injury in an automobile accident. Other mechanisms of injury include direct blows to the lateral aspect of the hip as in a fall from a height or a side impact automobile collision. PMID- 7791942 TI - Cervical dystonia: a review the role of botulinum toxin. AB - Cervical dystonia, although rare in the general population, can severely affect the lives of those afflicted with the disease. Throughout history several theories have been proposed regarding its etiology and pathophysiology, from underlying mental disorders to post-infectious to altered basal ganglia and brainstem function. However, CD remains poorly understood. Because of its similarity to Idiopathic Torsion Dystonia a genetic basic is suspected, but is not proven. Without a true understanding of the disease treatment remains symptomatic, and begins with physical therapy and medications and progresses to consideration of surgery. These treatment strategies have provided some relief, which is usually less than satisfactory within a short period of time. Recently, the use of botulinum toxin has provided significant symptomatic relief of pain in CD and has been associated with subjective and objective improvement in head posture. This newest therapy, although symptomatic, restores a more normal head posture and pain relief enabling the individuals with CD to continue to be active and productive participants in life, providing a ray of hope to these people as we continue to search for a better understanding of the disease process and the development of more effective treatment strategies. PMID- 7791946 TI - Sensory nerve conduction studies in children. Age-related changes of conduction velocities. AB - Normal values of sensory conduction velocities (CV) in four routinely examinated peripheral nerves are presented median, ulnar, radial and sural were gathered from the intact side of children with unilateral brachial plexus or different peripheral nerve lesions aged from two weeks to 15.5 years. The data were computer treated using an exponential function as the one which best reflects the dynamics of CV age-related changes i.e. its neurophysiological maturation. Approximated exponential curves and standard error, 95 per cent of confidence limits were computer-fitted to CV values and computer-plotted for each nerve. The values of sensory CV were computed for each month of age. The minimum and maximum values of CV (CVo, CVmax), the age when CV reaches 95% of its maximum maturity (age 95%), and maturation rate constant-k were computed for each nerve and used for comparative assessment of their neurophysiological maturation. In addition the increase of CV per month during the period equal to age 95% was calculated. The results have shown: 1. Values of CV along the segment wrist to elbow in newborns (CVo) and after maturation (CVmax) were found to be significantly higher than those along the distal fingers to wrist segment of both median and ulnar nerves (p < 0.001). The main reason for this is probably temperature difference between these two segments. 2. Smaller variations of CV values found in different nerves along the same nerve segment can be caused by measurement or other technical error. Besides, in case of infants it is also very important that age groups are identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791945 TI - Linguistic development in a patient with Landau-Kleffner syndrome: a nine-year follow-up. AB - A longitudinal linguistic analysis of aphasic disorder in a 15-year-old boy affected by Landau-Kleffner syndrome followed since the age of 6 is reported. The phonological, morphosyntactic and lexical levels of verbal deficits have been evaluated by means of collected samples of spontaneous language and a battery of linguistic tests. The clinical course has fluctuated with improvement and worsening of aphasia and epilepsy; at the end of the follow-up the boy was seizure-free and a medium-degree disturbance in language production and comprehension was present. The results of the linguistic evaluation suggest that the aphasic disturbance was related to a deficiency in phonological decoding which leads to phonological, morphosyntactic and lexical disturbances. A temporal relationship between the electroclinical picture and the aphasia has been observed: the persistent improvement in linguistic performances took place only after the disappearance of the seizures and of the EEG epileptic anomalies during sleep. PMID- 7791947 TI - Somatosensory and visual evoked potentials in congenital muscular dystrophy: correlation with MRI changes and muscle merosin status. AB - Congenital muscular dystrophy comprises a heterogeneous group of disorders, that have in common an early onset and a dystrophic picture on the muscle biopsy. The "pure" form of congenital muscular dystrophy is not associated with severe mental retardation or structural changes in the brain, though white matter changes on brain imaging have been detected in a significant proportion of cases. In this study we evaluated the incidence of sensory abnormalities (somatosensory and visual evoked responses) in a group of 17 patients with "pure" congenital muscular dystrophy and correlated the results of the evoked responses with the presence or absence of white matter changes on brain magnetic resonance imaging. Our results show close correlation between the presence of MRI white matter changes and abnormalities in the sensory evoked potentials. Conversely, all patients with normal brain MRI had normal somatosensory evoked potentials (SEP). Visual evoked potentials were less sensitive than somatosensory evoked potentials in detecting abnormalities in children with white matter changes on MRI. With the recent discovery of deficiency in merosin expression in the skeletal muscle of a subgroup of patients with CMD, we also correlated the presence or absence of white matter changes and the SEP responses with the merosin status. The results indicate that all merosin-negative patients had abnormal SEP as well as abnormal MRI, whilst no patient with normal merosin expression had an abnormal scan or abnormal SEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791948 TI - Moyamoya disease in three siblings--follow-up study with magnetic resonance angiography (MRA). AB - Three siblings with moyamoya disease including identical twins are reported. Although the younger of identical twins had no neurological problems, CT and MRI detected cerebral infarctions and cerebral angiography showed the typical features of moyamoya disease. All three cases underwent encephalo-duro-arterio synangiosis (EDAS), and serial magnetic resonance angiography (MRA) showed that the distal portions of the middle cerebral artery (MCA) were well perfused through surgically created anastomoses. There were no findings of disease progression. MRA might play an important role in follow-up studies of moyamoya disease. PMID- 7791949 TI - Band brain heterotopia. Case report and literature review. AB - The authors describe the case of an 11-year-old boy with a neuroradiologic pattern of band gray matter heterotopia, clinically characterized by epileptic seizures as well as normal psychomotor development. The clinical history and neurophysiological and neuroradiological investigations are reported. The diagnosis is based on brain magnetic resonance (MR) imaging, which has proved to be the most specific and sensitive test to describe neuronal migration disorders. Possible treatments are discussed. PMID- 7791950 TI - Cerebellar and brainstem hypoplasia in a child with a partial monosomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10. AB - A child with hypoplasia of the cerebellum and brainstem in association with an unbalanced translocation, resulting in a partial deletion of the short arm of chromosome 5 and a partial trisomy of the short arm of chromosome 10, is described. A balanced translocation was present in his mother and maternal grandmother. A maternal uncle had died at the age of 4 years with the same clinical picture. After reviewing the literature, we conclude that the monosomy 5p is the most likely cause for this malformation. We suggest that the possible existence of chromosomal anomalies should always be considered in the differential diagnosis of hypoplasia of the cerebellum and/or brainstem. PMID- 7791952 TI - Molybdenum-cofactor deficiency: CT and MR findings. AB - We describe the CT and MR findings in molybdenum-cofactor deficiency, a rare metabolic disorder which is caused by the defect of a molybdenum-containing enzyme cofactor. The CT (3 patients) and/or MR studies (3 patients) of 4 children, which became symptomatic with intractable seizures within the first days after birth and finally turned out to have molybdenum cofactor deficiency, were reviewed. All patients showed multicystic leukencephalopathy and a normal newborn pattern of myelination of the brainstem. A striking finding in some studies was an abnormal shape of the frontal horns of the dilated ventricles caused by severe volume loss of the basal ganglia, especially of the caudate nucleus, and of the corpus callosum. MRI was superior to CT in the demonstration of these lesions. In molybdenum-cofactor deficiency, which can be diagnosed by a typical laboratory pattern, CT and MR show the findings of severe perinatal brain damage. The abnormal shape of the frontal horns, although possibly not specific, may even suggest molybdenum-cofactor deficiency in newborns with intractable seizures. PMID- 7791951 TI - Treatment of "benign" partial epilepsies of childhood, including atypical forms. AB - In a retrospective study the results of therapy in 60 children with so-called benign partial epilepsies are reported. It has been shown that the assessment of the therapeutic effect has to include the EEG, especially in epilepsies with atypical course. Carbamazepine has no effect on the EEG, in epilepsies with atypical course (atypical benign partial epilepsy, Landau-Kleffner syndrome, epilepsy with continuous spikes and waves during slow sleep [CSWS]) carbamazepine usually has no effect either on the seizures or on the EEG, on the contrary, in some cases both may even get worse. In our experience, the drug of choice in all types of benign childhood epilepsy is sulthiame, if necessary in combination with clobazam. Other drugs previously administered, including carbamazepine, should be dropped quickly. If the treatment with sulthiame or sulthiame/clobazam in children with atypical course is not effective, ACTH-therapy should be considered as soon as possible. These results should be confirmed in a prospective randomized study. PMID- 7791953 TI - Metachromatic leukodystrophy and coincidental finding of papillomatosis of the gallbladder. A case report. AB - In this case report we describe the coincidental finding of polyps in the gallbladder by ultrasound investigation in a six-year-old girl, known to have metachromatic leukodystrophy. The investigation was carried out because of suspicion of abdominal trauma after falling down the stairs and finding elevated serum amylase. PMID- 7791954 TI - Modulation of motor activity patterns and sleep states in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns. AB - To evaluate the influence of prematurity and postnatal age on the relationship between motor activity (MA) and sleep states, forty clinically and neurologically normal infants were recorded polygraphically and grouped according to their gestational (GA, prematures: < 36 weeks, full-term: 37-41 weeks) and conceptional (CA, 37-38 and 39-41 weeks) ages. Sleep states (active: AS, and quiet: QS) were defined by the concordance of EEG and rapid eye movement criteria. Movements of both upper (UL) and lower (LL) limbs were independently recorded. In all groups the amount of MA in both UL and LL clearly predominated in AS compared with QS (p < 0.02). Contrariwise, both the longest period without movement and the no movement 20-sec epochs were significantly higher in QS than in AS (p < 0.005). In AS, age-related modifications and modulation of MA amount throughout the state were similar for PRT and FT groups: a) in both groups a significant decrease of MA with advancing CA was observed (p < 0.05); b) MA throughout the state was randomly distributed regardless of CA. In QS, however, PRT were distinguishable from FT by the absence of: a) a significant decrease of MA amount with advancing CA, together with a reduced increase of both the longest period without movements and the no-movement 20-sec epochs; b) prevalence of MA in LL compared with UL; c) modulation of the distribution of MA throughout the state. PMID- 7791955 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 7791956 TI - An immunoelectron microscopic study of methionine-enkephalin structures in cat prevertebral ganglia. AB - Methionine-enkephalin-like immunoreactivity was detected in presynaptic nerve fibers and SIF cells in cat prevertebral ganglia. The immunoreactive nerve fibers contained a mixture of numerous small clear vesicles and a few large vesicles; the immunoreactivity was only confined to the large vesicles. Most of the immunoreactive fibers were in apposition with non-immunoreactive neuronal profiles, without any detectable synaptic membrane specializations. The other immunoreactive fibers formed synaptic contacts mainly with non-immunostained dendrites and to a lesser extent with axons and neuronal soma. The characterization at the ultrastructural level of the enkephalin-like immunoreactive structures is discussed as regards the modalities whereby opiates may be involved in sympathetic ganglionic transmission. PMID- 7791957 TI - Substrate- and inhibitor-specificity of a non-endothelial enzyme which forms [Met5]-enkephalin from [Met5]-enkephalin-Arg6,Phe7 in isolated rabbit ear artery: pharmacological characterization. AB - The captopril-inhibited enzyme which forms [Met5]-enkephalin from [Met5] enkephalin-Arg6,Phe7 in isolated rabbit ear artery was characterized further by using various natural substrate candidates/analogues ([Met5]-enkephalin-Arg6,Phe7 and its amide, [Met5]-enkephalin, angiotensin I and bradykinin), peptidase inhibitors such as captopril, enalaprilate and thiorphan and by endothelial removal. 10(-5) and 10(-4) M but not 10(-6) M captopril reduced the effectiveness of [Met5]-enkephalin-Arg6,Phe7 and potentiated the effect of bradykinin but did not affect markedly the action of the other peptides. Of the inhibitors, enalaprilate was less effective than captopril, and thiorphan had no effect. The [Met5]-enkephalin-Arg6,Phe7-->[Met5]-enkephalin conversion was not affected by endothelial removal. The substrate and inhibitor spectrum of this non-endothelial enzyme activity bears no relationship in other, hitherto characterized dipeptidylcarboxypeptidases/endopeptidases known to be involved in the metabolism of the tested peptides. PMID- 7791958 TI - Mode of action of an inhibitory neuropeptide SchistoFLRFamide on the locust oviduct visceral muscle. AB - The possible mode of action of an inhibitory neuropeptide SchistoFLRFamide (PDVDHVFLRFamide) on locust oviduct visceral muscle was studied by examining its ability to inhibit calcium ionophore A23187-, caffeine- or phorbol ester-induced oviduct contractions. A23187-induced muscle contractions included two components: one which required the influx of extracellular Ca2+ through Ca2+ channels (blocked by cobalt ions), the other not blocked by cobalt ions. SchistoFLRFamide inhibited the cobalt-sensitive components, but not the latter. Caffeine induced two phases of contractions, a phasic contraction which was probably due to the release of intracellular Ca2+ and a tonic contraction which required the influx of extracellular Ca2+. SchistoFLRFamide inhibited the tonic contraction in a dose dependent manner but did not influence the phasic contraction. The phorbol 12 myristate 13-acetate-induced muscle contraction required the presence of extracellular Ca2+, with Ca2+ probably entering through ligand-gated channels, but the contraction was not inhibited by SchistoFLRFamide. Based upon these results, it appears that SchistoFLRFamide inhibits muscle contraction by preventing the accumulation of free intracellular Ca2+ from extracellular stores. SchistoFLRFamide is incapable of inhibiting contraction induced by the release of intracellular stores of Ca2+. It is possible that SchistoFLRFamide closes or blocks voltage-gated and some ligand-gated Ca2+ channels in the plasma membrane. PMID- 7791959 TI - Characterization of a serine peptidase responsible for the inactivation of endogenous cholecystokinin in human brain. AB - Depolarization of slices of human cerebral cortex releases cholecystokinin-8 immunoreactivity, only a fraction of which is recovered in intact immunoreactive form in the medium. This suggests that extensive hydrolysis takes place during short incubations. In the presence of diisopropylfluorophosphate, a serine reagent, the recovery is nearly doubled, however, consistent with the involvement of a serine peptidase activity. The latter was characterized by assessing the protective effects of a series of serine protease inhibitors belonging to the families of peptide chloromethylketones or boronic acids. The relative potency of these inhibitors was similar to corresponding values previously found with rat brain slices indicating that a similar serine peptidase activity is responsible for endogenous cholecystokinin inactivation in the two species. PMID- 7791960 TI - Involvement of vasopressin and corticotropin-releasing hormone in VIP- and PHI induced secretion of ACTH and corticosterone. AB - The relative roles of hypothalamic corticotropin-releasing-hormone (CRH) and vasopressin (AVP) as mediators of the stimulant effect of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) on ACTH and corticosterone (CORT) secretion, were examined using receptor blockade of endogenous CRH and AVP. ACTH and CORT secretion were stimulated 6- and 7-fold, respectively, by PVN infusion of VIP (3.0 nmol) and 6- and 9-fold, respectively, by PHI (3.0 nmol). ACTH and CORT stimulation by VIP were inhibited 78 and 72%, respectively, by pretreatment with the CRF antagonist, 59 and 57%, respectively, by pretreatment with the AVP antagonist and about 78% by combined pretreatment with the CRF and AVP antagonists. PHI-induced stimulation of ACTH and CORT was inhibited 89 and 81%, 73 and 59% and 93% by pretreatment with the CRF- or AVP-antagonist or combined administration, respectively. These results support the hypothesis that the activation of the hypothalamic-pituitary-adrenal (HPA) axis by VIP and PHI is mediated through the release of endogenous CRH. AVP also plays a role in this response, possibly by enhancing the activity of CRH in a synergistic manner. PMID- 7791961 TI - Role of endogenous opioid peptides in central glucocorticoid receptor (GR) induced decreases in circulating LH in the male rat. AB - While it has been shown that intracerebral administration of exogenous glucocorticoids diminishes pituitary luteinizing hormone (LH) release, it is not known if these hormones act directly on gonadotropin-releasing hormone (GnRH) synthesizing neurons, or if their central inhibitory effects are mediated by specific neural substrates. In the present study, we examined whether the opioid receptor antagonist, naltrexone (NALT), alters patterns of LH release elicited by either systemic or intracerebroventricular (i.c.v.) delivery of GR agonists. Subcutaneous (s.c.) injection of the GR agonist, RU362 (2.5 mg/kg), promoted a significant reduction in circulating LH levels; pretreatment by i.c.v. injection of 1.0 microgram NALT, however, attenuated this inhibitory hormonal response. It was also found that rats treated sequentially with NALT and RU362 exhibited significantly lower plasma LH levels compared to rats injected with NALT alone. In other experiments, intracranial delivery of the synthetic glucocorticoid, dexamethasone (DEX), into either the ventricular system or the hypothalamic ARC resulted in significantly decreased plasma LH concentrations; the central inhibitory effects of DEX on peripheral LH release were reversed, however, by i.c.v. pretreatment with NALT. In summary, the present studies show that opioid receptor blockade attenuates systemic, as well as intracerebral inhibitory effects of GR agonists on the GnRH-pituitary LH axis, suggesting that circulating glucocorticoids inhibit LH, in part, through central actions involving endogenous opioid receptors. The observed decline in peripheral plasma LH following intra ARC injection of DEX suggests that local GR may be functional target sites for glucocorticoid effects on LH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791962 TI - [125I]-BQ3020, a potent ETB-selective agonist, displays species differences in its binding characteristics. AB - Binding of [125I]-BQ3020 to membranes prepared from rat cerebellum, dog lung and CHO cells stably transfected with the human endothelin ETB receptor clone was specific, saturable and of high affinity. The apparent dissociation constants (KdS) were 63, 53 and 112 pM for rat cerebellum, dog lung and human ETB, respectively. The maximum bindings (Bmax) were 3.8, 0.430 and 20 pmol/mg protein for rat cerebellum, dog lung and human clone, respectively. Competition binding experiments using [125I]-BQ3020 and unlabelled ET-1, ET-3, S6c and BQ123 indicated that ET-1, ET-3 and S6c competed for [125I]-BQ3020 binding with similar high affinity (IC50 approximately 0.3 nM), whereas BQ123 was ineffective in competing for [125I]-BQ3020 binding. Time course experiments suggested that the binding of [125I]-BQ3020 to all three preparations was rapid, and reached steady state by approximately 40 min at 30 degrees C. Addition of excess unlabelled ET-1 resulted in partial dissociation (25-40%) from human ETB and dog lung receptors, whereas from rat cerebellum it was essentially irreversible. These data suggest that [125I]-BQ3020 is a potent and selective ETB agonist and its reversible binding property is species-dependent. PMID- 7791964 TI - Candidal pituitary abscess: case report. AB - We report a case of a culture-proven intrasellar Candida albicans abscess. A 36 year-old woman presented with a history of headaches, menstrual irregularities, and mild symptoms of diabetes insipidus. She was neurologically intact at the time of a transsphenoidal surgery for a presumed pituitary adenoma. An extensive work-up revealed that although the patient was seronegative for human immunodeficiency virus, she was immunocompromised with a T-cell dysfunction. Fungal abscesses of the pituitary gland have rarely been reported. This is the first documented case of a patient who is seronegative for human immunodeficiency virus who becomes infected by an ordinarily innocuous fungus, Candida albicans. PMID- 7791963 TI - Attenuation of traumatic cell death by an adenosine A1 agonist in rat hippocampal cells. AB - In a rat hippocampal cell culture, we studied the mechanism of adenosine-mediated neuroprotection in traumatic injury to neurons. When the processes and bodies of cells in culture were mechanically disrupted, neurons that were located at a distance from the damage site died. This secondary neuronal death is at least partially mediated by glutamate, because MK801, a specific N-methyl-D-aspartate glutamate channel blocker, diminished the toxic effect. Furthermore, cyclopentyl adenosine, a specific A1 adenosine receptor agonist that specifically attenuates synaptic release at the excitatory terminal, also blocked this trauma-mediated cell death. The dissemination of neurotoxicity from cell injury implies a release of a toxin by the dying cells. Consistent with this hypothesis, we found that neurotoxicity could be transferred to an uninjured neuronal culture by applying extracellular solution of the damaged culture to the healthy undamaged culture, as long as the fluid was transferred within 5 minutes. However, the glutamate concentrations in this medium were never higher than 20 nmol/L, suggesting that glutamate is not mediating the soluble and transferable toxicity. Consistent with this observation, the transferable neurotoxicity was not blocked by MK801 but was effectively blocked by cyclopentyl adenosine. Our observations suggest that traumatic cell death in culture is mediated by multiple mechanisms, including glutamate excitotoxicity. PMID- 7791965 TI - Thickening of the pituitary stalk: a finding suggestive of intrasellar tuberculoma? Case report. AB - We describe the case of a patient with an exclusively intrasellar mass, disclosed because of a left sixth nerve palsy and headaches. No other manifestation of disease, namely, endocrinological, was present. The lesion was approached transsphenoidally, and the pathological examination revealed a tuberculoma. Complete removal was achieved, and the patient started postoperative antituberculous therapy. In some circumstances, thickening of the infundibulum and the pituitary stalk could preoperatively suggest the diagnosis of hypophysial tuberculoma. PMID- 7791967 TI - Teratoma of the cavernous sinus: case report. AB - We report the case of an infant with a mature teratoma of the lateral wall of the cavernous sinus. A complete excision of the tumor was achieved. There was no evidence of recurrence at 1-year follow-up examination. Intracranial teratomas and the anatomy of the lateral wall of the cavernous sinus are briefly reviewed. To our knowledge, this is the first case of a teratoma confined to the cavernous sinus. PMID- 7791966 TI - Lymphocytic hypophysitis: case report. AB - We report a rare case of lymphocytic hypophysitis in a 52-year-old man who presented with a combination of hypopituitarism and diabetes insipidus. Magnetic resonance imaging with a contrast medium revealed an expanding sellar mass and thickening of the pituitary stalk with homogeneous enhancement. These findings may be useful in differentiating lymphocytic hypophysitis from pituitary adenoma. The unique clinical and radiological features of this case are discussed. PMID- 7791968 TI - Total resection of torcular herophili hemangiopericytoma with radial artery graft: case report. AB - A case of recurrent hemangiopericytoma involving the torcular herophili is reported, with special reference to the reconstruction of the straight sinus with a radial artery graft. In preoperative investigations, the tumor was found invading the straight and transverse sinuses. The involved occipital superior sagittal sinus had been removed in the previous surgery. A collateral bypass was observed from the superior sagittal sinus to the straight sinus, and the veins of Rosenthal were not opacified, suggesting poor venous drainage from the deep venous system to the cavernous sinus. We considered it necessary to reconstruct the straight and right transverse sinuses to achieve total removal of the tumor. The affected sinuses were removed and were successfully reconstructed with a radial artery interposition graft between the straight and right transverse sinus. The postoperative course was good, and the bypass was patent on the postoperative angiogram. The details of the operative technique are described. PMID- 7791970 TI - Regional cerebral oxygen saturation during intra-arterial papaverine therapy for vasospasm: case report. AB - Cerebral arterial vasospasm continues to be a major secondary medical complication of aneurysmal subarachnoid hemorrhage. Despite hypervolemic hemodilution, arterial hypertension, and pharmacological therapy, morbidity and mortality due to vasospasm remain high. The authors discuss a patient with vasospasm who did not respond to traditional medical therapy and who underwent intra-arterial papaverine infusions while being monitored with transcranial cerebral oximetry. Oximetry during the procedure revealed significant improvements in brain regional saturation of oxygen, with the relief of vasospasm that correlated with clinical improvements in the patient's neurological status. Transcranial cerebral oximetry was used to monitor regional oxygen saturation throughout the angiographic and interventional procedures, providing continuous, real-time, clinically relevant information about the effects of vasospasm and its treatment. PMID- 7791971 TI - An endoscopic approach to cysticercosis cysts of the posterior third ventricle. AB - An attempted removal of a third ventricular cysticercosis cyst by an endoscopic approach was aborted before surgery when a preoperative scan demonstrated migration of the cyst into the fourth ventricle. In a second case, successful endoscopic removal of a cysticercosis cyst of the posterior third ventricle by a precoronal, transforaminal approach is described. Transforaminal endoscopic removal of third ventricular cysticercosis lesions is feasible, and immediate preoperative imaging should be performed to rule out migration of the lesion before surgery. PMID- 7791969 TI - Idiopathic spinal cord herniation: a treatable cause of the Brown-Sequard syndrome--case report. AB - Symptomatic herniation of the spinal cord through the dura is an uncommon clinical problem. Since 1989, we have encountered three patients who each presented with an unexplained, longstanding Brown-Sequard syndrome and were found to have idiopathic herniation of the thoracic spinal cord. This report describes the clinical, radiographic, and surgical findings in these three patients and reviews the five previously reported patients with this syndrome. Idiopathic herniation of the spinal cord is a treatable cause of the Brown-Sequard syndrome that may be more common than is currently recognized and should be known to all surgeons managing spinal disorders. PMID- 7791972 TI - Implantation of fetal tissue for the management of Parkinson's disease: a technical note. AB - A relatively simple method for implanting fetal tissue within the human basal ganglia is described. Stereotactic techniques are used to deposit 14 to 16 strands of fetal mesencephalic tissue in a linear array within the putamen bilaterally. To eliminate the need for targeting each needle pass independently, we have devised a novel rotating template/micromanipulator apparatus that can be mounted on a Cosman-Roberts-Wells stereotactic frame. The template contains two parallel columns of nine holes, all spaced at 4-mm intervals. It can be aligned to the longitudinal axis of the putamen and targeted with coordinates for the center point of the putamen. Surgery is performed on an awake patient. Short-term morbidity (4-6 wk) in the form of variability of Parkinsonian signs, particularly "off" symptoms and mild confusion, appears to be the rule with simultaneous bilateral implants. PMID- 7791974 TI - Library: historical perspective. PMID- 7791973 TI - Illumination of mastoid air cell for suboccipital craniotomy: technical note. AB - The mastoid air cell was illuminated to estimate the location of the sigmoid sinus in 12 cases of a retrosigmoid suboccipital craniotomy for cerebellopontine angle tumors. A special illuminator system was designed, and the tip of the illuminator was placed inside the external auditory canal. The posterior margin of the illuminated air cell was delineated on the outer surface of the skull after the skin flap was turned and the position of the sigmoid sinus was estimated with reference to the preoperative computed tomographic scan. The posterior margin of the mastoid air cell in an axial slice, including the internal auditory canal, usually exists within the breadth of the sigmoid sinus. A gap between the posterior margin of the mastoid air cell and the position of the sigmoid sinus was easily corrected by the computed tomographic finding. This method was found to be simple and reliable in performing the suboccipital craniotomy with safety and exactness. PMID- 7791975 TI - Meta-analysis of antibiotic prophylaxis. PMID- 7791976 TI - Surgical management of orbital cavernous angiomas: prognosis for visual function after removal. PMID- 7791977 TI - Vascular considerations and complications in cranial base surgery. PMID- 7791978 TI - Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. AB - The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5 year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7791980 TI - Recurrent subarachnoid hemorrhage from untreated ruptured vertebrobasilar dissecting aneurysms. AB - The clinical characteristics of vertebrobasilar dissecting aneurysms occurring with subarachnoid hemorrhage (SAH) were reviewed in 42 patients, with particular focus on the time, incidence, and outcome in association with subsequent rupture. Twenty-nine patients underwent 31 surgical procedures, and the remaining 13 patients were managed without surgery. Surgical details included 19 proximal vertebral artery obliterations (including 1 case of endovascular surgery using balloon occlusion), 9 trappings, 1 wrapping, 1 bleb clipping, and 1 bleb clipping combined with wrapping. Surprisingly, subsequent rupture occurred in 30 (71.4%) of the 42 patients. Excluding one patient with postoperative rupture, 29 patients suffered a subsequent rupture in the unsecured stage. Of these 29 patients, 19 were operated on after the subsequent rupture and 10 were not operated on because of deteriorated clinical condition (9 patients) or anatomic considerations (1 patient). Of the 30 patients that suffered a subsequent rupture, 14 died. Twelve of the deaths were directly related to the second episode of rupture. Of the 12 patients who did not suffer a subsequent rupture, 10 underwent operations and there were no operative deaths. Only one patient died as the result of the initial critical SAH. The mortality (46.7%) of the patients with subsequent rupture was significantly higher (P < 0.05) than that (8.3%) of the patients without subsequent rupture. Seventeen (56.7%) of the 30 subsequent ruptures occurred within 24 hours after the first SAH, and 24 (80%) occurred within the first week. Six (66.7%) of the 9 patients operated on within 24 hours after the first SAH and 11 (68.8%) of the 16 patients operated on within a week suffered preoperative subsequent ruptures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791979 TI - Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost. AB - A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791981 TI - Proximal balloon occlusion for dissecting vertebral aneurysms accompanied by subarachnoid hemorrhage. AB - Five patients with spontaneous dissecting vertebral aneurysms presenting with subarachnoid hemorrhage were treated with endovascular proximal balloon occlusion after a successful balloon Matas' test. Occlusion was performed in the extracranial portion of the vertebral artery after the potentially dangerous period of cerebral vasospasm. Two patients rebled preoperatively during the waiting period. Although angiograms demonstrated residual aneurysmal dilatation for four of the five patients, postoperative hemorrhages or progression of the dissection were not observed during the 19- to 48-month follow-up period. Only one patient experienced transient postoperative ischemic complication. Although the timing of the procedure and the site of occlusion remain controversial, proximal balloon occlusion of the vertebral artery appears to be a safe and effective therapy for patients with dissecting vertebral aneurysms presenting with subarachnoid hemorrhages. This method provides an important, less invasive alternative for this condition. PMID- 7791983 TI - Long-term results of surgical treatment of idiopathic neuralgias of the glossopharyngeal and vagal nerves. AB - Physicians disagree about the best surgical treatment for patients with idiopathic neuralgias of the glossopharyngeal and vagal nerves after medical treatment has failed. Some favor percutaneous thermal rhizotomy, and other prefer extracranial section of the glossopharyngeal or branches of the vagal nerve, intracranial section of the glossopharyngeal and upper vagal rootlets, or microvascular decompression. However, the results of these procedures are limited to series with follow-up periods of less than 5 years or to series with longer follow-ups that were performed before the microneurosurgical era. We reviewed the long-term results of 14 patients with vagoglossopharyngeal neuralgia treated surgically at our center between 1976 and 1987 to determine the best treatment. Sixteen procedures were performed: 2 percutaneous thermal rhizotomies; 2 extracranial sections of the superior laryngeal nerve; and 12 intracranial glossopharyngeal and upper vagal rhizotomies, 4 with and 8 without microvascular decompression. The follow-ups ranged from 4 to 17 years (mean, 10 yr). All 14 patients who underwent percutaneous or intracranial rhizotomies were pain free. Two patients who underwent percutaneous rhizotomies developed persistent dysphagia and hoarseness. Both patients who underwent extracranial nerve section experienced pain recurrence 2 and 4 years later. Of 12 patients who underwent intracranial section of the glossopharyngeal and upper vagal rootlets, 2 developed dysphagia, which resolved completely in 1 patient and persisted mildly in the other; 1 had transient hoarseness; and 2 developed frequent coughing episodes, which persisted in 1 patient and resolved completely in the other. Side effects due to motor vagal deficits may be eliminated by intraoperative monitoring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791982 TI - Functional magnetic resonance imaging mapping of the sensorimotor cortex with tactile stimulation. AB - The purpose of this study is to compare tactile stimulation of the palm with voluntary movement of the fingers as paradigms for mapping the sensorimotor cortex in functional magnetic resonance imaging. In 22 subjects, 24 sets of functional magnetic resonance images were obtained with echoplanar acquisitions and cross-correlation image processing techniques. Two tasks were employed: a motor task in which subjects moved the thumb and index finger of one hand and a sensory task in which the palm was scratched by another person. The activation from the two tasks coincided entirely in 20 sets and partially in 3 sets. In one case, no activation was seen with the motor task. The study suggests that tactile stimulation of the palm is useful and reliable for mapping the sensorimotor cortex. PMID- 7791984 TI - Early postoperative appearance of radiofrequency lesions on magnetic resonance imaging. AB - Eleven patients who underwent stereotactic radiofrequency lesions in the central nervous system had magnetic resonance imaging follow-up within 72 hours of surgery to determine the early appearance of their lesions. Eight patients with severe tremor, one with chronic pain, and two with dystonia were analyzed. There were six female patients and five male patients, age 7 to 75 years (mean +/- standard deviation = 42 +/- 21). Magnetic resonance imaging was performed postoperatively at 32 +/- 25 hours (range, 3-72). Postoperative T1-weighted spin echo images demonstrated foci of iso- to hyperintensity surrounded by an edge of hypointensity, and corresponding T2-weighted images showed a lesion with three concentric zones consisting of inner hypointense, middle hyperintense, and outer hypointense zones. Gadolinium increased T1-weighted image lesion visibility, and a ring of enhancement around the zone of hypointensity was observed. Lesions could be seen as early as 3 hours after surgery. The lesions were best shown on gadolinium-enhanced T1-weighted images and on T2-weighted images. The edema surrounding the lesion increased over time, up to the 72 hours studied. These data provide important information on the development of lesion appearance, which may be applied in the development of real-time magnetic resonance imaging monitoring of radiofrequency lesion formation. This technique associated with electrophysiological response and the real-time visualization of the anatomic correlation of the probe may allow for a very precise and selected lesion in the central nervous system for the treatment of functional disorders and brain tumors. PMID- 7791985 TI - Disappearance of arachnoid cysts after head injury. AB - The mechanism of the disappearance of arachnoid cysts is not fully understood. This article discusses the spontaneous disappearance of these cysts after head injury. Five patients underwent computed tomography and were diagnosed as having a subdural hematoma or effusion associated with arachnoid cysts. In four of the five patients, the cyst decreased in size or disappeared. These cases suggest a possible mechanism by which this type of cyst associated with subdural hematoma or effusion might disappear. For the arachnoid cyst to disappear, the rupture of the cyst wall appears to be essential, and after rupture, subdural effusion must develop around the cyst. As this effusion is absorbed, the fluid in the cyst drains away, after which the cyst becomes smaller and gradually disappears. This hypothesis supports the possibility of a "natural cure" for arachnoid cysts without surgical intervention. PMID- 7791986 TI - Continuous regional cerebral cortical blood flow monitoring in head-injured patients. AB - Continuous regional cerebral cortical blood flow (rCoBF) was monitored with thermal diffusion flowmetry in 56 severely head-injured patients. Adequate, reliable data were accumulated from 37 patients (21 acute subdural hematomas, 10 cerebral contusions, 4 epidural hematomas, and 2 intracerebral hematomas). The thermal sensor was placed at the time of either craniotomy or burr hole placement. In 15 patients, monitoring was initiated within 8 hours of injury. One third of the comatose patients monitored within 8 hours had rCoBF measurements of 18 ml per 100 g per minute or less, consistent with previous reports of significant ischemia in the early postinjury period. Initial rCoBF measurements were similar in the patients with Glasgow Coma Scale scores of 3 to 7 and in those with scores of 8 or greater. In patients with poor outcomes, rCoBF measurements did not change significantly from initial measurements; however, in those patients who had better outcomes, final rCoBF measurements were higher than initial rCoBF measurements. The patients who had better outcomes experienced normalization of rCoBF during the period of monitoring, and patients with poor outcomes had markedly reduced final rCoBF. These changes were statistically significant. When management was based strictly upon the intracranial pressure, examples of inappropriate treatment were found. For example, hyperemia and increased intracranial pressure treated with mannitol caused further rCoBF increase, and elevated intracranial pressure with low cerebral blood flow treated with hyperventilation increased the severity of ischemia. In 3 (5%) of 56 patients, wound infections developed. Continuous rCoBF monitoring in head-injured patients offers new therapeutic and prognostic insights into their management. PMID- 7791987 TI - Magnetic resonance imaging of titanium anterior cervical spine plating systems. AB - Magnetic resonance imaging (MRI) of titanium anterior cervical plating systems and their effect on postoperative images were evaluated ex vivo and in vivo. The Synthes and Caspar plating systems were examined by 0.5- or 1.5-T MRI scanners. A phantom study of these implants showed that in spin-echo modes, the plates and screws were seen as areas of signal loss accompanying a marginal hyperintense band, which was more obvious in higher tesla magnetic fields. Distortion of the magnetic field was more prominent in T2-weighted images. In gradient echo mode, the plate and screws were seen as areas of signal loss larger than the size of the metal because of the magnetic susceptibility effect. Postoperative MRI produced images of the implants similar to those observed ex vivo. The Synthes plating system did not interfere with the evaluation of the spinal cord, and the Caspar screw (which penetrated the posterior cortex of the vertebral body) caused a small artifact to be present at the anterior aspect of the spinal cord. In addition to being able to provide fixation of the cervical spine, titanium anterior cervical plates allow superior MRI of the postoperative spine. PMID- 7791989 TI - Gene expression from recombinant viral vectors in the central nervous system after blood-brain barrier disruption. AB - Direct intracerebral injection of recombinant adenoviral vectors within the brain parenchyma or the ventricular system results in a limited volume of distribution of virus, as demonstrated by transgene expression. Global delivery to the central nervous system may increase the use of these vectors but only if the viral vectors can cross the blood-brain barrier and result in transduction of the underlying cells. This short-term study examines whether osmotic disruption with mannitol can result in sufficient opening of the vascular endothelium to allow for passage of replication-defective adenovirus containing the Escherichia coli beta-galactosidase gene (lacZ). Virus was injected into the carotid artery of rats after blood-brain barrier disruption with intracarotid hypertonic mannitol, and the animals were killed and analyzed after 4 days. Histochemical analysis and electron microscopy confirmed expression of the E. coli lacZ gene in the pericapillary astrocytes of the ipsilateral cerebral cortex and deep grey matter. Furthermore, the extent of gene transfer and expression correlated with the degree of barrier opening, as measured by Evans blue staining. Transgene expression was not seen in control animals that received intracarotid saline before recombinant virus injection. These data demonstrate, for the first time, that blood-brain barrier disruption can allow for the delivery of functional viral vectors to the central nervous system. PMID- 7791988 TI - An experimental technique to induce and quantify complex cyclic forces to the lumbar spine. AB - The human spine is a complex, heterogeneous nonlinear and viscoelastic structure. In addition, in vivo loading is not uniaxial. Although many studies on the mechanical behavior of the spine under "pure" forces and single cycle load applications exist, little research is conducted with complex cyclic loads. In this study, we developed a technique to induce and quantify controlled complex physiological loads to the lumbar spinal column under cyclic (chronic) conditions. The methods described include specimen preparation and mounting to induce controlled complex loading (cyclic compression-flexion vector was chosen as an example), instrumentation, and biomechanical data to achieve the objectives. The results indicated that the specimen sustained the external load in a combined compression-flexion mechanism without considerable off-axis forces (lateral shears) and moments (lateral bending and torsion). By mounting the anchoring bolt in appropriate places (such as an anterolateral placement to induce compression-flexion-lateral bending), this technique can be used to apply and continuously quantify complex physiological acute or cyclic loads to describe the biomechanics of the spine. This procedure of inducing complex loads eliminates the difficulty in applying the principles of superposition, using the response from individual "pure" forces to account for the nonlinearity and viscoelasticity of the human lumbar spinal column. PMID- 7791990 TI - The multiple tumor suppressor 1/cyclin-dependent kinase inhibitor 2 gene in human central nervous system primitive neuroectodermal tumor. AB - The recently described multiple tumor suppressor 1/cyclin-dependent kinase inhibitor 2 (MTS1/CDKN2) gene, encoding the cyclin-dependent kinase 4 inhibitor p16, is mutated in a wide variety of tumor cell lines, including gliomas. To investigate the possible role of this gene in the genesis of the central nervous system primitive neuroectodermal tumor (PNET), four established PNET cell lines and 18 PNET surgical specimens were studied for deletions and mutations of the MTS1/CDKN2 gene. One of the four cell lines had homozygous deletion of the gene. No mutation in any of the three MTS1/CDKN2 exons was detected in the other three cell lines by single strand conformational polymorphism analysis. Eighteen surgical PNET specimens were studied for allelic and homozygous deletion at chromosome 9p21, the location of the MTS1/CDKN2 gene. No loss of heterozygosity was noted in 11 of the tumors, and no homozygous loss was noted in any tumor. Single strand conformational polymorphism analysis of the entire coding region of the MTS1/CDKN2 gene revealed no mutation within MTS1/CDKN2 in any tumor. Although deletion of MTS1/CDKN2 may occur in some PNET cell lines, neither deletion nor mutation of the gene is found in tumors before culture. The genesis of the human central nervous system PNET does not involve deletion or mutation of the MTS1/CDKN2 gene. PMID- 7791991 TI - A pial window model for the intracranial study of human glioma microvascular function. AB - A new model for human brain tumor uses the intracranial placement of tumor xenografts under transparent glass cranial windows in nude rats, which require no immunosuppression for tumor engraftment. Adult male nude rats underwent implantation of human anaplastic astrocytomas (D-54 MG in 10 rats, D-317 MG in 11 rats). The tumors were placed on the pial surface of the left cerebral hemisphere under a glass cranial window overlying the cranium. Six control animals underwent cranial window placement alone. Tumor volumes were estimated from direct measurements of tumor dimensions, revealing a mean doubling time of 1.58 days for the D-54 MG tumors and 2.62 days for the D-317 MG tumors. When tumor volume estimates reached 35 mm3, photomicrographs revealed tumor vasculature in each tumor cell line that was distinct from both the other xenograft and the normal brain parenchyma. Qualitative differences in vascular appearance were supported by length/density coefficient calculations in each study group, with D-317 MG demonstrating the highest vascular density. Vessel caliber tended to be smaller in D-54 MG tumors than in D-317 MG tumors. Laser-Doppler measurements of local blood flow in tumors and normal parenchyma revealed significantly lower blood flow in both tumor cell lines than in control brain. Evaluation of leukocyte/endothelial cell interactions indicated more leukocyte rolling in D-54 MG tumors than in D-317 MG tumors; no evidence of this cell interaction was found in normal pial vasculature. This model allows direct serial inspection of human brain tumor growth and vascular function in an experimental animal and could be used to study tumor vascular and inflammatory responses to a variety of therapeutic manipulations. PMID- 7791992 TI - A canine model of acute hindbrain ischemia and reperfusion. AB - Animal models of brain stem ischemia are needed for pathophysiological study and evaluation of treatment; few such models are available currently. A new canine model of hindbrain ischemia and reperfusion is introduced in this article. Through an anterior cervical approach, the basilar artery was surgically exposed in 18 dogs. The posterior communicating and superior cerebellar arteries were embolized with cyanoacrylate glue to isolate the posterior circulation from the anterior circulation. Reversible hindbrain ischemia was induced in 14 dogs by the temporary clipping of the vertebral and ventral spinal arteries for various periods (10-30 min), then the clips were removed and reperfusion was achieved for 5 hours. In all 14 dogs, the hindbrain ischemia was confirmed by the decreased perfusion pressure in the basilar artery (< 10 mm Hg), the diminished regional cerebral blood flow as measured with a laser Doppler flowmeter at the medulla oblongata (< 10 ml/100 g/min), the flattened brain stem auditory evoked potentials, and the increased leakage of Evans blue dye from tissue. These parameters did not change in the four control dogs. The changes in brain stem auditory evoked potentials were closely related to the length of ischemic interval; after 10 minutes of ischemia, reperfusion fully reversed the changes in brain stem auditory evoked potentials, but 20-minute and 30-minute ischemic intervals partially or totally depleted the brain stem auditory evoked potentials. Delayed postischemic hypoperfusion occurred in all five dogs that underwent the 30-minute ischemic interval. The early physiological changes in this model allowed us to estimate the severity of brain stem ischemia and the resulting damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791993 TI - Intraischemic hypothermia decreases the release of glutamate in the cores of permanent focal cerebral infarcts. AB - The cerebroprotective effects of hypothermia in focal models of ischemia are well established, but little is known about the underlying mechanisms of this form of brain protection. Cortical cooling in global transient ischemic models suggests that hypothermia limits glutamate excitotoxicity by decreasing the release of glutamate during ischemia. Few studies have examined glutamate release in the more physiological model of permanent focal ischemia. In this study, we used a rat model of middle cerebral artery occlusion (MCAO) of permanent focal ischemia. Extracellular glutamate concentration was analyzed bilaterally by microdialysis for 30 minutes before MCAO to 120 minutes after MCAO. Normothermic animals (n = 13) had a baseline glutamate concentration of 9.23 +/- 2.5 mumol/ml (mean +/- standard error of the mean) before MCAO. Extracellular glutamate rose quickly after vessel occlusion and peaked at 33.95 +/- 6.3 mumol/ml 30 minutes after MCAO. By 60 minutes after MCAO, this level had decreased to 25.14 +/- 6.3 mumol/ml; glutamate levels decreased slightly to 21.35 +/- 6.8 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had an initial extracellular glutamate concentration of 5.22 +/- 1.3 mumol/ml before MCAO. This value rose gradually to a maximum of 10.69 +/- 3.3 microns/ml at 50 minutes after MCAO and then returned to a baseline value of 2.58 +/- 1.2 mumol/ml by 120 minutes. Contralateral control glutamate dialysates in the normothermic and hypothermic groups remained near baseline throughout the experimental period. The mean percentages of right hemispheric volumes occupied by infarcts were 11.96 +/- 1.68% in the hypothermic group and 19.77 +/- 2.03% in the normothermic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7791994 TI - Fluid intelligence after frontal lobe lesions. AB - Generally positive correlations between different ability tests provide the evidence for a factor of "general intelligence" or Spearman's g. Though a possible neural substrate for g is suggested by executive impairments following frontal lobe lesions, preserved IQs in some frontal patients have been taken as strong evidence against this interpretation. We show that such results depend on how g is measured. Patients with superior IQs on the most clinically popular test -the Wechsler Adult Intelligence Scale--show impairments of 20-60 points on conventionally measured fluid intelligence or novel problem solving. On psychometric grounds, it is fluid intelligence that is most closely related to Spearman's g. The data suggest that g may in large part be a reflection of frontal functions. PMID- 7791995 TI - Functional separation of global and local stereopsis investigated by cross adaptation. AB - Reports that brain lesions may differentially affect global and local stereopsis suggest that anatomically separate mechanisms underlie these two functions. We demonstrate here that adaptation to global stereograms induces an after-effect on local stereopsis as well as on global stereopsis, showing that the two mechanisms cannot be entirely separate. We suggest that global stereopsis depends upon an interaction between primary visual area V1 and higher brain areas such as inferotemporal cortex. PMID- 7791996 TI - The effects of frontal- or temporal-lobe lesions on susceptibility to interference in spatial memory. AB - Patients with unilateral frontal- or temporal-lobe lesions and normal control subjects studied multiple arrays of pictures and were tested for recall of the locations of the pictures. One condition consisted of three trials of the same pictures in different spatial arrangements, recall being tested immediately after each presentation. In a second condition (using different stimuli), the subject was given two trials with one set of pictures, but a new set of pictures was viewed on the third trial. All groups showed a build-up of proactive interference across trials using the same pictures, and a release of proactive interference when they studied new pictures. Patients with frontal-lobe lesions were more susceptible to proactive interference than were the other groups. PMID- 7791997 TI - Visual scanning behavior in patients with homonymous hemianopia. AB - This study examined oculomotor scanning behavior in 60 patients suffering from homonymous hemianopia due to postgeniculate damage. Eye movements were recorded using an infra-red recording technique during performance of a visual searching task. In 24 patients (40%) scanning behavior was found to be normal; the remaining 60% showed significantly increased search times. Detailed analysis of patients' eye movements revealed that the pronounced slowing of visual scanning was mainly due to the disordered spatial organization of scanning not only in the affected, but also, to a lesser degree, in the intact hemifield. CT and NMR examination revealed that additional damage to the ipsilateral posterior thalamus or the parieto-occipital cortex results in impaired spatial organization of visual scanning. A smaller group of patients (n = 14) with impaired visual scanning was treated to improve the spatial organization of visual exploration. After training, all patients showed a significant improvement in visual searching, indicating that successful oculomotor adaptation can substitute the lost visual hemifield. It is argued that impaired visual scanning in hemianopic patients is mainly caused by visual spatial disorientation which also affects spatial integration of visual information processing. PMID- 7791998 TI - Perceptual completion in patients with drawing neglect: eye-movement and tachistoscopic investigations. AB - A group of neglect patients was compared with control patients in the perception of complete and incomplete figures, including the patients' own incomplete drawings. Eye movements were recorded throughout. Under both tachistoscopic and free-vision conditions, the neglect patients failed to report the absence of the left side of figures only when this missing side lay in the left visual field; they always reported the absence of the left side when the right half-stimulus lay entirely within the right visual field. Thus, the position of a stimulus in the visual field is an important factor in explaining neglect. PMID- 7791999 TI - Mutism and auditory agnosia due to bilateral insular damage--role of the insula in human communication. AB - We report a case of transient mutism and persistent auditory agnosia due to two successive ischemic infarcts mainly involving the insular cortex on both hemispheres. During the 'mutic' period, which lasted about 1 month, the patient did not respond to any auditory stimuli and made no effort to communicate. On follow-up examinations, language competences had re-appeared almost intact, but a massive auditory agnosia for non-verbal sounds was observed. From close inspection of lesion site, as determined with brain resonance imaging, and from a study of auditory evoked potentials, it is concluded that bilateral insular damage was crucial to both expressive and receptive components of the syndrome. The role of the insula in verbal and non-verbal communication is discussed in the light of anatomical descriptions of the pattern of connectivity of the insular cortex. PMID- 7792000 TI - The role of prefrontal regions in the Stroop task. AB - The Stroop is a classical paradigm that presumably involves the inhibition of automatic responses and is frequently used to assess the frontal lobe functions. We investigated the effect of discrete prefrontal lesions in a Stroop task. A sample of 32 patients with frontal lesions were matched with normal controls by sex, age and years of education. Significant differences between patients and controls were found for errors but not for reaction time. Regression analysis showed that the region most related to errors was the right prefrontal lateral cortex. Left lobectomies did not impair the Stroop performance. Our results favour the role of the right prefrontal cortex in sustained attention, and disagree with the conception of the left prefrontal cortex having a role in the inhibition of verbal automatic responses. PMID- 7792001 TI - Clock-drawing in a case of left visuo-spatial neglect: a deficit of disengagement? AB - A patient (C.B.) with severe left visuo-spatial neglect and hemianopia after right hemisphere stroke was tested on three conditions of a clock-drawing task. Either on spontaneous drawing or when the number sequence was provided by the experimenter, C.B. drew a clockface with left-sided numbers transposed to the right side of the dial. By contrast, when each number was drawn on a separate dial, its location was correct and there was no transposition. Directional hypokinesia or a representational deficit cannot explain these effects. It is proposed that a deficit in disengaging attention from right-sided visual stimuli plays a critical role in some forms of number transpositions. PMID- 7792003 TI - Impaired movement sequencing in patients with Huntington's disease: a kinematic analysis. AB - This experiment asked whether Huntington's disease, like Parkinson's disease, another disorder of the basal ganglia, causes a specific progressive deficit in the performance of sequential movement. Ten patients with Huntington's disease and their age-matched controls wrote the lower-case letter "l" four times in a linked cursive script, upon a graphics tablet which sampled pen position at 200 Hz. Kinematic features of sequential movement (stroke length, stroke duration, peak velocity, time to peak velocity and time from peak to zero velocity) were examined in a Group by Stroke Position (2 x 8) design, to identify which aspects of movement might show progressive disturbances. Unlike Agostino et al. [Brain 115, 1481-1495, 1992], this experiment did in fact find progressive changes in the performance of sequential movements. Kinematic analysis indicated a progressive increase in movement duration during sequential movement, that was associated with the accelerative phase of movement. PMID- 7792002 TI - Performance on motor tasks as an indication of increased behavioral asymmetry with advancing age. AB - Age-related asymmetrical functional decline was tested on a sample of 64 right handed volunteers between 60 and 64 years of age who were free from neurological illnesses and physical handicaps. Increase in functional asymmetry was explored by examining performance indexes for each hand and superiority of the dominant hand on motor tasks of different complexities: the Finger Tapping Test, the Grooved Pegboard Test, and the Pin Test. Our study revealed an increase in superiority of the right hand with age on a highly demanding task (Pin Test). This finding is discussed in light of the hypothesis of a decline in callosal functioning with age and the alternative hypothesis of a greater vulnerability of the right hemisphere in the elderly. PMID- 7792005 TI - Release from proactive interference in early Alzheimer's disease. AB - The study analyses the performance of 22 mild Alzheimer's disease (AD) patients on the Release from Proactive Interference (RPI) paradigm with the aim to investigate the relationship of RPI with frontal function. Twenty-one normal elderly subjects, age and education matched, constituted the control group. Patients with AD were found to recall less words on each trial of the RPI than did the controls. The analysis of Proactive Interference (PI) and Release from PI, in AD patients, by using Anova (trial x group), showed a significant effect of trial and group but not a group by trial interaction. These results indicate a similarity between the performance of AD patients and normal controls on the Release from Proactive Interference paradigm. Despite the similar pattern of performance, AD patients were significantly inferior to normal controls with regard to global performance level. The AD patients' scores on "frontal lobe" tests were correlated with an index of RPI (shift condition index). The only significant result was with the number of categories on the Wisconsin Card Sorting Test, suggesting a weak correlation between RPI and "frontal lobe" function. PMID- 7792004 TI - Ocular space exploration in the dark and its relation to subjective and objective body orientation in neglect patients with parietal lesions. AB - Eye movements of neglect patients with right parietal lesions were recorded during ocular searching for a (non-existent) target in complete darkness. With respect to the objective orientation of the sagittal midplane, ocular exploration was biased toward the ipsilesional side. However, in relation to the patients' subjective localization of the sagittal midplane in space, exploratory eye movements were symmetrically distributed to the subjective "left" and "right" as observed in non-brain-damaged controls. The present results further support the hypothesis that the essential aspect leading to spatial neglect is a disturbance of those cortical structures that are crucial for computing egocentric, body centred coordinates that allow use to determine our body position in space and that are necessary for visuomotor coordination and exploration of space. In neglect patients the central coordinate transformation seems to work with a systematic error resulting in a deviation of the spatial reference frame to the ipsilesional side. Consequences of this deviation are a displacement of subjective localization of body orientation and--to the same degree--of the spatial area in which motor behavior (here exploratory eye movements) is executed. PMID- 7792006 TI - Increased activation as a limiting factor of performance in sharp shooters. AB - The measurement of autonomic nervous system (ANS) activity was performed on 10 male and five female sharp shooters (rifle) during competitions. Electrodermal, thermovascular, cardiorespiratory variables and two indices of performance were recorded simultaneously. When the subjects fired shots that hit the target, they had a higher number of negative skin potential responses than when they missed. The responses had lower amplitude but lasted longer than when the shots missed the target. Good performance seemed to depend on high levels of motivation (increase in negative potential response), better mastery of the emotional reactivity (low amplitude response), and greater concentration time (increased duration of response). PMID- 7792007 TI - Disturbances of cortical development. AB - The development processes coinciding in formation of cerebral cortex were presented. On this background may arise the cortical developmental abnormalities. The review of principal cortical malformations include the 1) agyria-pachygyria - lissencephaly type I, 2) polymicrogyria, 3) disorganized cortical structure - lissencephaly type II, 4) minor cortical developmental anomalies and 5) other cortical dysplasia syndromes. It will help to reconstruct the pathomechanism of cortical abnormal development from early occurring primary errors to late changes in which coincide necrotic lesions. The presented material illustrate the role of time of occurrence and intensity of damage in final result of pathologic developmental processes. PMID- 7792008 TI - Ammon's horn changes in focal brain ischemia in humans. AB - Neuronal changes in Ammon's horn were examined immunocytochemically in 20 patients aged from 51 to 101 years, deceased in the course of ischemic lesions localized within the area supplied by vessels derived from other then Ammon's horn vascularization (middle cerebral artery). Numerous neurons within various sector of the pyramidal layer, in the dentate gyrus, subiculum and entorhinal cortex were immunopositive in reaction with antibodies to serum proteins (albumin, IgG, alpha-1-antitrypsin), indicating their damage. The distribution of damaged Ammon's horn pyramidal cells differed from the location of injured Ammon's horn neurons in experimental investigations of brain ischemia and did not indicate a selective vulnerability of pyramidal cells in the human h1 area, corresponding to the CA1 sector in animals. Contrary to experimental material, changes in the human Ammon's horn are caused by numerous overlapping factors. PMID- 7792009 TI - Cyclic GMP levels in the rat brain and plasma during clinical death and after resuscitation. AB - Changes of cGMP content in the rat brain and plasma have been evaluated by means of the radioimmunologic method after 5-min clinical death and up to 2 hours after resuscitation. Ischemia produced a decrease of cGMP in the brain, however, at the 15th min after resuscitation a reversible significant rise of nucleotide concentration was noted. In plasma at the end of ischemia and in the postischemic period a significant decrease of cGMP level was observed. The mechanisms of cGMP regulation in the central nervous system and the significance of the obtained results are discussed. PMID- 7792010 TI - Ultrastructural evaluation of neuronal damages induced by low doses of quinolinic acid in dissociated hippocampal culture. AB - The effect of a subtoxic level of quinolinic acid (QUIN) on the morphological picture of the rat hippocampus in dissociated cultures was investigated. Addition of 50 microM of QUIN to the culture medium induced only slight advanced and reversible changes of the postsynaptic elements, whereas the majority of pyramidal neurons were undamaged. The results suggest that subtoxic concentration of QUIN is insufficient to produce stable depolarization of cell membranes and severe neuronal damage. PMID- 7792011 TI - Hemiballismus in patient with blastic phase of chronic myelogenous leukemia. AB - The authors report the clinical course and neuropathological findings in the case of hemiballismus due to leukemic infiltration of the subthalamic nucleus. The symptoms were observed in a 19-year-old patient with blastic phase of chronic myelogenous leukemia, two weeks before death, when what is called the "critical point" developed (white cell count beyond 100 G/l and thrombocytopenia less than 50 G/l). The investigation are considered to confirm the role of the "critical point" in the development of central nervous system leukemic complications. PMID- 7792012 TI - Effect of chronic administration of sodium valproate on the morphology of the rat brain hemispheres. AB - Effective doses of sodium valproate (200 mg/kg) applied in rats chronically (1, 3, 6, 9 and 12 months) evoked the first morphological changes in the brain hemispheres after 9 months of drug administration. Structural abnormalities of the brain tissue consisted in disseminated nonspecific neuronal lesions and patchy nerve cell loss, more pronounced in the final phase of the experiment. The neuronal lesions were localized predominantly in the 3rd and 5th layers of the neocortex and in the pyramidal cell layer of the hippocampus. They were accompanied by vascular wall alterations, perivascular tissue damage, as well as by microvacuolar changes and spongy degeneration of the subpial and periventricular regions. Vasogenic character of parenchymal changes is stressed by the authors. The possible influence of liver damage on the development of brain pathology is discussed. PMID- 7792013 TI - [The "natural" history of ischemic cardiopathy, Incidence of coronary events in the follow-up of 114 ambulatory patients]. AB - In the last decade advances in cardiovascular research improved remarkably our understanding of coronary heart disease. However many important problems are so far unresolved. In the present study we focused on the "natural" history of ischemic heart disease in a group of 114 patients. One hundred-seven patients had recent myocardial infarction, and seven suffered from angina. They were observed for a mean period of five years (one to 168 months). Forty-nine patients (42.9%) had no coronary events; sixty-five had angina, myocardial infarction or both. The myocardial infarction was however rare (five cases). The most frequent presentation of angina was stable and effort angina, which sometimes subsided after a period of presence. The classification of angina was often very difficult in cases of effort angina with very low threshold. No relevant differences were found between patients with and without coronary events according to age, sex, duration of follow-up, location of previous myocardial infarction. A significant difference was found in the prevalence of risk factors only for hypertension, which was more frequent in patients with coronary events. Smokers were more frequent in group without coronary events. In our opinion, the most interesting conclusion is that, almost half of these patients remained completely asymptomatic for a very long period. PMID- 7792014 TI - [Complementary echo flow imaging and digital angiography in the supra-aortic area for indication and intervention of carotid revascularization in 1587 subjects in the OPI (Stroke Prevention) program]. AB - The availability of non invasive carotid ultrasound imaging techniques actually allows planning and carrying on of large screening programs for detection of atherosclerotic carotid occlusive disease. The aim of non invasive ultrasound patient selection is to limit the practice of invasive carotid angiography only to patients for whom carotid endarterectomy is likely to be a therapeutic choice. PURPOSE. Testing the efficacy of sequential use of color coded echo flow imaging (echo color Doppler: ECD) and arterial digital angiography (ADA) respectively in the second and third phases of a screening program for detection and treatment of carotid occlusive disease in a resident population (OPI program). METHODS. From January 29th 1990 through March 31st 1992, 1,587 subjects underwent ECD out of 16,379 subjects that participated in the first level investigations. 404 of these (25.5%) were affected with carotid occlusive disease, 271 (17%) had inframural non stenosing carotid lesions and 228 (14.3%) carotid kinkings. At ECD, 71 showed lesions as severe as to be susceptible of surgical operation and underwent ADA. The percentage of carotid stenosis was calculated on the ADA imagins, applying the method suggested by the North American Symptomatic Carotid Endarterectomy Trial. RESULTS. Overall sensitivity and specificity of ECD versus ADA were 94% and 95.2% respectively. Cases in which ECD overestimated the lesion as compared to ADA results were recorded as false positive, while cases in which ECD underestimated the lesion were recorded as false negative. CONCLUSIONS. Both ultrasound imaging and ADA are useful in screening programs for carotid occlusive disease: informations different and complementary to the definition of the lesions can be obtained from each procedures in subsequent phases. Morphologic findings of carotid ECD are essentially consistent with ADA, thus allowing to carry on safely non invasive long-term follow-up programs for operated subjects as well as for people bearing carotid lesions originally not susceptible of surgical treatment. PMID- 7792016 TI - [Hyperuricemia and cardiac risK factors: epidemiologic study in the aged]. AB - The aim of our study is to evaluate whether hyperuricemia may be considered a cardiovascular risk factor also in the elderly. 370 subjects over 60-years-old of both sexes were examined of which 148 presented an ischemic heart disease and 222, age and sex homogeneous, were considered as control group. Serum uric acid was determined. A strong difference among the two groups (p < 0.001) was statistically demonstrated. Such modifications were sex independent. A strict correlation of hyperuricemia and hyper trygliceridemia was present; in fact high uric acid levels were mostly found in the group with triglycerides > 200 mg/dl (p < 0.02). In the whole group and in males a stability of uric acid was noted. In females a significant increase among the first (60-69 years) and the second (70 79 years) age class was present. In conclusion, a positive role of hyperuricemia in the ischemic heart disease pathogenesis is possible. PMID- 7792015 TI - [Structural and morphometric analysis of the internal mammary artery used in coronary bypass surgery]. AB - The internal mammary artery is currently regarded as the optimal canal in coronary bypass surgery. Even if the motives for the excellent behaviour of this artery are still not fully clarified, the morphological and morphofunctional study of its wall can contribute to explain the clinical results obtained using this canal. In order to complete existing studies on this topic and to increase our knowledge of the structure of this artery, segments of internal mammary artery taken from patients undergoing coronary bypass surgery were analysed. Histological, immunohistochemical, histochemical and morphometrical tests were performed in these samples. The results of the tests underline the considerable complexity of the internal mammary artery whose walls appear to be rich in elastic fibres, divided into numerous lamellar structures concentric to the vasal lumen and without vasa vasorum in the tunica media given that this is adjacent to the tunica adventitia. Moreover, the marked presence of the NO-synthase enzyme, responsible for nitrogen monoxide synthesis, was observed in the endothelial layer and tunica media, as suggested by histochemical analysis. These data argue in favour of a structure able to resist the considerable hemodynamic stress to which the artery is subjected after bypass, a structure which is functionally well adapted to receive the majority of nutrition through its own lumen, and, lastly, a structure capable of self-regulation in response to the requirements made from time to time. These findings may further our understanding of the morphofunctional aspects of the internal mammary artery and may contribute to explaining the latter's relative immunity to atherosclerosis and, thus, its success in coronary bypass. PMID- 7792017 TI - [Comparative characteristics of electrocardiographic tracing in young subjects of various ethnic groups]. AB - In this study we evaluated the potential differences in normal electrocardiographic parameters between two groups of young patients belonging to different races (Caucasians and Blacks). For this purpose 100 electrocardiograms had been taken, coded and compared in 50 Italian males and 50 north-Africans who came to an Emergency Department because of minor condition. On the whole we could not find significant differences between the two groups, except for a small increase in P-wave duration in black people. We conclude that the same parameters used to evaluate normal electrocardiograms in white people, may be satisfactory applied also for black individuals. This fact is worthy of attention since more and more extracomunitarian patients are addressing the Italian Health Service. PMID- 7792018 TI - [CoQ10 blood levels and erythrocyte concentration of GSH in ischemic heart patients during exercise test (effects of vitamin E)]. AB - During exercise there is an increase of oxygen consumption with production of superoxide anion. Tocopherols and ubiquinones are intrinsic lipid components involved in antioxidant protection and also glutathione reduced is an important water soluble antioxidant. The authors take into consideration 28 patients with ischemic heart disease coming in a rehabilitation center. In a group of 14 of them we studied the effects on the exercise ergonometer test of administration of 1200 mg of tocopherol on the behaviour of ubiquinone plasmatic levels and GSH. In this group CoQ10 after exercise increase significantly (0.762 SD 0.134 g/ml before vs 0.827 SD 0.89 after). GSH doesn't increase after (2.5 SD 0.459 mM/l vs 2.492 SD 0.457). In the group of patients without tocopherol after exercise CoQ10 decrease significantly (-39%) and also GSH has the same behaviour (-15%). Our study shows that the administration of tocopherol prevents lipoperoxidation occurring during exercise test. PMID- 7792019 TI - [Atrial fibrillation induced by massage of the carotid sinus in patients with orthodromic reciprocal supraventricular tachycardia and Wolff-Parkinson-White syndrome]. AB - A 46 years old man with WPW syndrome, due to a posteroseptal accessory pathway, was admitted because of orthodromic reciprocating tachycardia, 210/m'in frequency. At the end of the carotid sinus massage, for accomplish the conversion of tachycardia to sinus rhythm, the orthodromic reciprocating supraventricular tachycardia degenerated into atrial fibrillation associated with high ventricular rate and the presence of hemodynamic instability, reverted to sinus rhythm by intravenous propafenone. Vagal stimulation, induced by carotid sinus massage, probably caused dispersion of atrial refractorines and intraatrial reentry, converting the orthodromic tachycardia into atrial fibrillation. The transesophageal electrophysiologic study, executed in treatment with propafenone, not documented the accessory connection and atrial fibrillation or reciprocating tachycardia were not inducible. PMID- 7792022 TI - Is there a role for specific anti-TNF strategies in glomerular diseases? PMID- 7792020 TI - [Myocardial infarct without Q wave in the elderly: diagnostic evaluation using vectorcardiography]. AB - The diagnosis of previous non-Q wave myocardial infarction by standard electrocardiographic investigation is uncertain, particularly in elderly patients because of concomitant disease. We have studied 31 elderly patients (aged 63-72 years) with a diagnosis of non-Q wave myocardial infarction between 1-6 months after this acute event. The patients underwent clinical-anamnestic examination, standard electrocardiography, vectorcardiography according to the Frank system and M-mode and 2-D echo-cardiography with continuous and pulsated Doppler. The ECG showed ST-T anomalies in 12 patients (38.7%) whereas the VCG showed anomalies of QRS-loop normal convexity in 27 patients (87%) and 16 of these (51.6%) showed bites criteria (duration > or = 10 msec, voltage > or = 0.1 mV, present at least on two planes). By echocardiography, regional hypo-akinesia was observed in 19 patients (61.3%). Although bites are not only present in myocardial infarction, they indicate an interruption of myocardial gradual electric activation, compatible with fibrous areas, and should be evaluated as a part of the clinical anamnestic, laboratory and instrumental data. PMID- 7792021 TI - Chemoattractive cytokines (chemokines) and immune renal injury. PMID- 7792023 TI - Are continuous therapies superior to intermittent haemodialysis for acute renal failure on the intensive care unit? PMID- 7792024 TI - Hyperlipidaemia of the nephrotic syndrome--the search for a nephrotic factor. PMID- 7792025 TI - Resistance of parathyroid cell to calcitriol as a cause of parathyroid hyperfunction in chronic renal failure. PMID- 7792026 TI - Subtotal nephrectomy: a mosaic of growth factors. AB - We have studied the distribution of immunoreactive growth factors, by an avidin biotin-peroxidase technique, throughout the course of progressive renal scarring in rats submitted to extensive renal ablation. Groups of rats (n = 6) were sacrificed at Days 7, 15, 21, 30, 90 and 150 following subtotal nephrectomy (SNx) by ligation and resection of the renal poles. During the early stages, when compensatory renal growth took place, increased renal immunostaining for insulin like growth factor-I (IGF-I) and epidermal growth factor (EGF) was detected within the collecting ducts and distal tubules, respectively. As renal scarring became established by Days 90 and 150, these two growth factors were detected within the cells of damaged and vacuolated distal tubules. By contrast, a progressive increase immunostain for platelet-derived growth factor (PDGF)-AB was apparent within the glomeruli from Day 15 onward preceding the onset of glomerulosclerosis. A third staining pattern was apparent by Day 15 for transforming growth factor-beta (TGF-beta) and by Day 30 for IGF-I consisting of a perivascular and interstitial distribution coinciding with adventitial expansion and tubulo-interstitial fibrosis, respectively. A mosaic of growth factors is expressed within the kidneys of rats submitted to extensive renal ablation. PMID- 7792027 TI - Endotoxins modulate chronically tumour necrosis factor alpha and interleukin 6 release by uraemic monocytes. AB - We examined in vivo the release of tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) by uraemic monocytes upon stimulation with endotoxin contaminated bicarbonate concentrate. Twelve uraemic patients underwent 1-month subsequent periods of standard haemodialysis (SHD) with cuprophane (CU), a high complement-activating membrane (6 patients), or haemodiafiltration (HDF) with polyacrylonitrile (PAN), a low-complement-activating membrane (6 patients), by using a dialysate prepared with either non-sterile bicarbonate concentrate tanks (phase 1) or sterile bicarbonate concentrate bags (phase 2). TNF alpha and IL-6 concentrations were determined in monocyte supernatants by ELISA; endotoxin levels in bicarbonate concentrates were measured by a chromogenic limulus amoebocyte lysate (LAL) assay. A significant increase in LAL reactivity was found in bicarbonate concentrate tanks compared to sterile bags (P < 0.001). Non sterile dialysate caused a significant (P < 0.001) predialytic increase in monocyte TNF alpha release as compared to controls and non-dialysed uraemic patients. One month treatment with sterile bicarbonate significantly decreased TNF alpha predialytic activity in monocyte supernatants (P < 0.001) to levels closer to those of non-dialysed uraemic patients. A similar decrease was observed for IL-6 production. Dialytic treatment induced a further increase in both TNF alpha and IL-6 production, particularly in phase 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792028 TI - Interactions between sodium balance, intrarenal dopamine synthesis, and sympathetic activity in HLA-identical kidney donors and recipients. AB - Intrarenal dopamine (DA) synthesis, sympathetic activity and sodium homeostasis were studied in eight HLA-identical kidney recipient and donor pairs at 50, 150, and 300 mmol sodium intake. Trimethaphan was given intravenously (i.v.), to mimic acute denervation, tyramine i.v. to induce noradrenaline (NE) release, and the DA precursor DOPA i.v. to study DOPA to DA conversion. Blood pressure was higher in the recipients (P < 0.05) and was not influenced by sodium intake. Cumulative sodium balances were not different between the groups. Sodium intake did not affect DA excretion in either group. The recipients had higher DA (P < 0.05) and DOPA (P < 0.01) excretions and lower urinary DA over DOPA ratio (UDA/DOPA, P < 0.01) and lower NE excretion (P < 0.05) during the whole study. High sodium intake suppressed the UDA/DOPA in both groups (P < 0.05). Trimetaphan decreased renal vascular resistance (RVR) and increased sodium excretion only in the donors (P < 0.05), while GFR increased in both groups. During HiSo tyramine increased RVR in the recipients (P < 0.01) and UDA/DOPA in the donors (P < 0.05). DOPA infusion increased DA excretion four to fivefold but did not change sodium excretion in either group. It is concluded that the recipients maintained sodium homeostasis well but seem to have an impaired functional innervation of the transplanted kidney. NE release seem to stimulate intrarenal DOPA to DA conversion. In both groups a direct relation between DA and sodium excretion was lacking. PMID- 7792029 TI - Tuberous sclerosis complex with end-stage renal failure. AB - Renal angiomyolipoma is common in the tuberous sclerosis complex (TSC), the classic features of which are facial angiofibroma, seizures, and mental retardation. We report a family with three affected members demonstrating the wide spectrum of TSC-associated lesions ranging from asymptomatic findings to life-threatening complications. The predominant symptoms of the index patient were hypertension and mild renal insufficiency at age 48, resulting in end-stage renal failure at age 63 due to giant bilateral angiomyolipoma of the kidneys. The two TSC-affected siblings had died years previously, one from pulmonary lymphangioleiomyomatosis and the other during an epileptic state; the latter had situs inversus totalis as another remarkable finding. The diagnosis of TSC may be overlooked if CNS symptoms are absent and if cutaneous lesions are masked by cosmetic procedures, as occurred in the index case. Chronic renal failure due to angiomyolipoma is not widely known to clinical nephrologists, but develops in approximately 15% of TSC patients. Displacement of functional renal parenchyma by abnormal tissue appears to be the major pathogenetic mechanism leading to end stage renal failure. Angiomyolipomas can be diagnosed from this characteristic sonographic pattern and the demonstration of fatty tissue in CT or MRI. Multiple renal cysts are also common in TSC. Therefore TSC should be considered in the differential diagnosis of polycystic kidney disease. PMID- 7792030 TI - Lipids and lipoprotein(a) as risk factors for vascular disease in patients on renal replacement therapy. AB - A large cohort of patients on renal replacement therapy were screened for the presence of symptomatic arterial disease affecting the coronary, cerebral or peripheral circulations. Ninety-two of 325 patients were found to have vascular disease. Those with vascular disease had significantly higher median lipoprotein(a) [Lp(a)] levels than those without (38.4 vs 14.2 mg/dl, P < 0.001), with a preponderance of Lp(a) levels greater than 30 mg/dl (58% vs 25% P < 0.001). Apolipoprotein(a) [apo(a)] isoform distribution was similar between the groups, but those with vascular disease had higher Lp(a) levels in the S2, S3/S4 and S4 isoform types. Comparison of 76 matched pairs of patients confirmed elevated Lp(a) levels in those with vascular disease. These patients also had significantly higher total cholesterol (6.66 vs 6.02 mmol/l) and low-density lipoprotein cholesterol (4.49 vs 3.86 mmol/l). Only Lp(a) was independently associated with vascular disease (P = 0.02). Elevated Lp(a) levels are significantly associated with the presence of vascular disease in patients on renal replacement therapy and may constitute another risk factor for the development of such disease in these patients. PMID- 7792031 TI - Cell cholesterol transport to plasma in blood from patients with renal failure or a kidney transplant. AB - Accumulation and distribution of cell cholesterol in plasma lipoproteins of incubated blood was examined in 36 patients with chronic renal failure including 13 who were dialysis-independent, 12 on haemodialysis, and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients, and 8 healthy controls. In addition, transport of cholesterol between red blood cells and high-density lipoprotein subfraction 3 (HDL3) isolated from a subgroup of patients with chronic renal failure was determined. Significantly less cell cholesterol appeared in plasma (P < 0.002) and HDL (P = 0.03), the main recipient of cell cholesterol, in patients with chronic renal failure compared with healthy subjects. Corresponding values in blood from renal transplant recipients were similar to controls. In patients with chronic renal failure, plasma HDL3 cholesterol levels (P < 0.02), HDL3 phospholipid content (P < 0.001) and net transport of red cell cholesterol to isolated HDL3 (P < 0.001) were significantly lower compared with controls. The data suggest that in patients with chronic renal failure, low levels of plasma HDL3 of abnormal composition may restrict the incorporation of cell cholesterol into the antiatherogenic HDL fraction potentially leading to inefficient transport of cholesterol from peripheral tissues and the development of atherosclerosis. These abnormalities appear to be reversed by renal transplantation. PMID- 7792032 TI - Parathyroid hormone and platelet cytosolic calcium concentration in essential hypertension. AB - To investigate the possible relationships between blood pressure, parathyroid hormone (PTH) and platelet cytosolic Ca2+ concentration ([Ca2+]i) in patients with essential hypertension, we studied 17 patients with this disease aged 48 +/- 2 years and 17 normotensive controls aged 44 +/- 3 years. Platelet [Ca2+]i was measured by spectrofluorimetry using the dye Fura-2 acetoxymethylester. Patients with essential hypertension displayed lower levels of serum ionized Ca2+ (0.99 +/ 0.03 versus 1.1 +/- 0.01 mmol/l, P < 0.05) and higher serum intact PTH levels (37 +/- 3 versus 26 +/- pg/ml, (P < 0.01) than the normotensive controls. Although serum levels of intact PTH were significantly correlated with mean arterial pressure (MAP) in the combined group of subjects (r = 0.42, P < 0.05), there was no correlation when each group was considered separately. Resting platelet [Ca2+]i was also higher in patients than in controls (57 +/- 3 versus 48 +/- 2 nmol/l, P < 0.005). When platelets were stimulated in vitro with thrombin, the increment in [Ca2+]i was also greater in patients than in controls in the presence of extracellular Ca2+ (264 +/- 24 versus 194 +/- 19 nmol/l, P < 0.05) but not in its absence (123 +/- 12 versus 112 +/- 10 nmol/l). The thrombin induced increment in [Ca2+]i was correlated with MAP in the hypertensive patients (r = 0.64, P < 0.01) and in the combined group of subjects (r = 0.42, P < 0.05). There was no relationship between resting or thrombin-induced [Ca2+]i and serum PTH in either group of patients or in the combined group of subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792033 TI - Role of protein adsorption on haemodialysis-induced complement activation and neutrophil defects. AB - The present clinical study investigated the role of protein adsorption on complement activation and neutrophil functions during in vivo haemodialysis. The parameters were measured simultaneously at the arterial and venous sites of a cuprophan (CU) dialyser with or without pretreatment with human albumin, human immunoglobulins or human total plasma proteins (PLP). Leukocyte count, complement activation (C3a des arg), oxygen radical production and chemotaxis were measured at time zero and 15 min at the arterial and venous sites of the dialyser. Leukopenia observed at both sites was prevented only with PLP treatment. Complement activation was maximal at the venous site, but was not prevented by any of the treatments. Neutrophil oxygen radical production and chemotaxis were significantly decreased only at the venous site and restored to normal with any of the three treatments. Complement activation was maximal at the venous site, but was not prevented by any of the treatments. Protein adsorption on the dialyser membrane seems to modulate the bioincompatibility parameters in a different way. Depending on the functions tested, the protein fractions have different protecting effects, indicating the multifactorial mechanism implicated in the CU haemodialysis-induced leukopenia, complement activation and neutrophil defect. PMID- 7792035 TI - Determination of the relation between alterations of total body water and thoracic fluid content during ultrafiltration by bioelectrical impedance analysis. AB - Total body impedance (TBI) is used to monitor alterations in total body water (TBW), e.g. during haemodialysis. However, 80% of the TBI signal is due to the resistance in extremities. Therefore TBI measurements give little information about alterations in thoracic fluid content (TF). Measuring both total body impedance and thoracic impedance (THI) can be a useful method to monitor TBW and TF changes during haemodialysis. In this study TBI and THI measurements were performed during 30 dialysis sessions and also in one group of 24 control subjects with normal tissue hydration. During haemodialysis TBI and THI significantly increased, demonstrating a decrease of TBW and TF. The ratio THI/TBI did not differ significantly during haemodialysis, indicating a similar effect of ultrafiltration on TBW and TF. The finding that TF decreased during haemodialysis was rather surprising, whereas pulmonary oedema is not an evident clinical problem in patients on maintenance haemodialysis treatment. THI measurements after dialysis proved to be significantly higher in comparison to the control subjects. This finding supports the hypothesis that the decrease in TF during dialysis is partly due to the sudden ultrafiltration-induced hypovolaemia leading to a fall in thoracic blood volume. ABBREVIATIONS: UF volume, ultrafiltration volume; TBI, total body impedance; THI, thorax impedance; TBW, total body water; TF, thoracic fluid. PMID- 7792034 TI - Risk factors for bacterial infections in chronic haemodialysis adult patients: a multicentre prospective survey. AB - All adult patients from 13 dialysis centres were prospectively followed up for 6 months in an attempt to appraise the current risk factors for bacterial infections in stable chronically haemodialysed patients. Parameters recorded as potential risk factors for BI were age, gender, cause of renal failure, time elapsed since the start of dialysis, history of transplantation, recent surgical procedure, previous bacterial infection, current immunosuppressive or erythropoietin therapy, type of angioaccess device, and serum ferritin level. Six hundred and seven patients (mean age 56.5 years, range 18-85) were enrolled in the study. Mean time elapsed since the start of dialysis was 4.7 years. One hundred and eighteen patients had developed at least one bacterial infection during the study period whereas 489 had remained free of bacterial infection at the end of the follow-up. In multivariate analysis three parameters were found to be significant and independent risk factors for bacterial infection: previous history of bacterial infection (at least one versus no previous episode), type of angioaccess device (catheter versus native fistula), and elevated serum ferritin level (greater versus lower than 500 micrograms/l). These results support the evidence that impaired host defences in chronic haemodialysis patients may be secondary to the dialysis procedure and suggest that the incidence of bacterial infection in these patients may be further reduced by appropriate supportive therapy. PMID- 7792036 TI - Surgical implantation of CAPD catheters: presentation of midline incision-lateral placement method and a review of 110 procedures. AB - One hundred-and-ten consecutive surgically implanted one-cuff straight peritoneal dialysis catheters in 103 adult patients over a 7 year period have been reviewed. All catheters were placed for chronic dialysis (CAPD). There were no early failures. Early complications consisted of one leak, 14 migrations, and two wound infections. In the long term 15 patients required transfer to haemodialysis (5 recurrent peritonitis, 7 unable to cope, 3 inadequacy of dialysis). Overall probability of catheter survival was 92.4% at 1 year and 82.4% at 2 years. The surgical implantation technique described provides a safe, reliable access for peritoneal dialysis with a low complication rate. PMID- 7792037 TI - Pyruvate anions neutralize peritoneal dialysate cytotoxicity. AB - A new peritoneal dialysate containing pyruvate anions was developed in order to avoid cytotoxic effect of conventional lactate-based dialysate. The dialysate has a final pH of 5.4 to 5.6 and is composed of 1.36-3.86% glucose-monohydrate; 132 mmol/l sodium; 1.75 mmol/l calcium; 0.75 mmol/l magnesium; 102 mmol/l chloride and 35 mmol/l pyruvate. For cytotoxicity testing peritoneal macrophages, and mesothelial cells (MC) were exposed to conventional lactate dialysate, and pyruvate dialysate. We investigated the O2- generation and cytokine synthesis after endotoxin stimulation in peritoneal macrophages and the proliferation of mesothelial cells of cultured human MC. After exposure to lactate dialysate O2- generation and cytokine synthesis in peritoneal macrophages and proliferation of mesothelial cells were inhibited when compared to solution containing pyruvate and the control solution. After preincubation with 3.86% glucose containing solutions, all negative effects became even more pronounced in the lactate group whereas after pre-exposure to pyruvate containing solution the toxic effects were absent. These results suggest that the acute toxic effects of commercially available peritoneal dialysates can be avoided by the use of sodium pyruvate instead of sodium lactate. PMID- 7792038 TI - Changes in bone mineral content during long-term CAPD. Indication of a sex dependent bone mineral loss. AB - Change in bone mineral content (BMC) was evaluated in a longitudinal trial comprising 12 women and 11 men with chronic renal disease treated with CAPD and 1 alpha-OH-D3 for 2 years. The patients served as their own controls. No patients were treated with steroids. Median age was 54 and 60 years for women and men respectively. No significant difference in 1-alpha-OH-D3 dosage or serum 1,25(OH)2D3 was found between the genders in the study period. Bone mineral content at the distal radius deteriorated significantly in the females with a median decrease of 12% over 2 years, i.e. approximately 6% per year (P < 0.001 and 95% confidence limits 8-20%). No significant change was noted in the males. There was no correlation between age and BMC change. Serum total alkaline phosphatase decreased nonsignificantly in both sexes. Total serum calcium increased significantly (P < 0.05) and serum phosphate decreased significantly (P < 0.05) in the women. Serum albumin and body weight decreased significantly in the males (P < 0.01 and P < 0.05) while no change was seen in the females. The demonstrated decrease in BMC in the female patients of approximately 6% per year exceeds the commonly observed loss of 1-2% per year in healthy women when measured with the same technique. Tentatively, the severe mineral loss in the women could indicate a sex-hormone-related disturbance in bone metabolism of uraemic females. PMID- 7792040 TI - Renal involvement in the hypereosinophilic syndrome. PMID- 7792039 TI - Acute renal failure due to accelerated hypertension following ingestion of 3,4 methylenedioxymethamphetamine ('ecstasy'). PMID- 7792041 TI - Alloimmune haemolytic anaemia after renal transplantation. PMID- 7792042 TI - Sterile peritonitis in a CAPD patient caused by a juxtaperitoneal abscess. PMID- 7792044 TI - The introduction of urine microscopy into clinical practice. PMID- 7792045 TI - Second symposium on uraemic toxicity. Summary of a symposium held in Gent, Belgium, 22-24 September 1994. PMID- 7792047 TI - The uraemic patient with multiple small sugillations on the forehead. PMID- 7792046 TI - Magnetic resonance image documentation of quadriceps tendon rupture. PMID- 7792048 TI - Seizures in dialysis patients treated with recombinant erythropoietin. PMID- 7792043 TI - Nephrology across the Atlantic: American election results indicate lurch to the right. PMID- 7792050 TI - Metformin-associated lactic acidosis in diabetic patients with acute renal failure. PMID- 7792049 TI - Treatment of Wegener's granulomatosis. A nephrologist's view. PMID- 7792051 TI - Prostaglandin E2 facilitates excitatory synaptic transmission in the nucleus tractus solitarii of rats. AB - Prostaglandin E2 (PGE2) binding sites are rich in the nucleus tractus solitarii (NTS). We studied the effects of PGE2 on evoked excitatory postsynaptic currents (eEPSCs) and miniature EPSCs (mEPSCs) in voltage-clamped neurons in rat NTS slices. eEPSCs and mEPSCs, mediated by non-NMDA glutamate receptors, fluctuated in size from event to event. In 37.5% of neurons, PGE2 increased the mean size of eEPSCs and changed the size distribution non-proportionally. In 42.9% of neurons, PGE2 increased the frequency of mEPSCs keeping the skewed size distribution unchanged. However, PGE2 did not modulate postsynaptic non-NMDA receptor sensitivity. We propose that size distributions of eEPSCs before and after PGE2 application are predictable from those of mEPSCs by quantal analysis with multinomial distribution. Our results suggest that PGE2 facilitates evoked and spontaneous release of glutamate vesicles. PMID- 7792052 TI - Expression of insulin receptor-related receptor mRNA in the rat brain is highly restricted to forebrain cholinergic neurons. AB - Insulin receptor-related receptor (IRR) is a member of the insulin receptor family. However, its endogenous ligand and the physiological roles of IRR are unknown. To elucidate the physiological roles of IRR in the brain, we examined the expression of its mRNA in the rat brain by in situ hybridization. In contrast to the widespread expression of insulin receptor and insulin-like growth factor-1 receptor mRNAs in the brain, the expression of IRR mRNA was highly restricted to the forebrain cholinergic neurons. All the forebrain cholinergic neurons expressed IRR mRNA. The present findings indicate that IRR has a selective role in the brain for forebrain cholinergic function. PMID- 7792053 TI - Adenosine triphosphate and arachidonic acid stimulate glycogenolysis in primary cultures of mouse cerebral cortical astrocytes. AB - Adenosine triphosphate (ATP) promotes glycogenolysis in primary cultures of mouse cerebral cortical astrocytes with an EC50 of 1.5 microM. A pharmacological analysis indicates an involvement of purinergic P2Y receptors in this action of ATP. Application of either arachidonic acid (AA), or certain unsaturated fatty acids, also results in glycogen breakdown. The EC50 of AA is approximately 50 microM. Thus ATP and AA can be added to the list of neuroactive agents that control glycogen levels in astrocytes, which includes noradrenaline, vasoactive intestinal peptide (VIP), adenosine and histamine. PMID- 7792054 TI - Vulnerability of the hippocampus to kainate excitotoxicity in the aged, mature and young adult rat. AB - Sensitivity to excitotoxic damage was assessed in young adult, mature and aged male Sprague-Dawley rats. Kainic acid was injected into the hippocampus and the size of the hippocampal lesion rated. Intrahippocampal injection of kainic acid produced lesions in aged animals that were significantly smaller than lesions in the young rats (P < 0.05), while lesion size in mature rats was intermediate. Excitotoxic damage was localized primarily to the CA3 region of the hippocampus in the aged rats. Young adult rats had more damage to the hippocampus with involvement of CA1 pyramidal and dentate granule cells. These results suggest that increased age may reduce susceptibility to excitotoxic damage. PMID- 7792056 TI - Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex. AB - In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure. PMID- 7792055 TI - No evidence for contribution of nitric oxide to spinal reflex activity in the rat spinal cord in vitro. AB - The effects of nitric oxide (NO) synthase inhibition, NO generation and an N methyl-D-aspartic acid (NMDA) receptor antagonist upon spinal reflex responses evoked by electrical activation of high threshold afferent fibres and brief application of NMDA have been compared in an in vitro preparation of the neonatal rat spinal cord. Reflex responses of spinal cords prepared from naive animals and those exhibiting a behavioural hyperreflexia following UV irradiation of the left hindpaw have been compared. C-fibre evoked and NMDA induced ventral root potential responses were significantly reduced by the selective NMDA receptor antagonist D-AP5 (40 microM) but completely unaffected by application of 7 nitroindazole (30 microM), NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) or sodium nitroprusside (50 microM) either in hyperalgesic or naive animals. In vivo behavioural experiments performed upon age-matched rat pups showed that reflex sensitivity was significantly reduced following administration of L-NAME (30 mg kg-1). The present study has failed to provide evidence that NO is involved in nociceptive spinal reflex activity measured in vitro. In contrast, an NO synthase inhibitor was shown to influence nociceptive reflex responses observed in vivo. We suggest it is possible that NO participates in post-injury induced hyperreflexia at sites other than directly upon spinal neurones. PMID- 7792058 TI - Alpha 2-adrenoceptor-mediated inhibition of capsaicin-evoked release of glutamate from rat spinal dorsal horn slices. AB - It is known that the descending noradrenergic system suppresses nociceptive transmission in the spinal dorsal horn. To determine whether noradrenaline-alpha adrenoceptor systems exert inhibitory influence on the release of glutamate from the nociceptive primary afferents, the effects of alpha-adrenoceptor agonists on the capsaicin (3 microM)-evoked release of glutamate from rat spinal dorsal horn slices were examined using an on-line continuous monitoring system for glutamate. The application of alpha 2-agonists clonidine (0.1-10 microM) and ST-91 (1 and 10 microM), respectively, decreased the capsaicin-evoked release of glutamate in a concentration-dependent manner. The partial alpha 2-agonist oxymetazoline (1 and 10 microM) produced a slight inhibition in the evoked release of glutamate. In contrast, the alpha 1-agonist phenylephrine (1 and 10 microM) did not show any significant effects on the evoked release of glutamate. The inhibitory action of 10 microM clonidine on the evoked glutamate release was antagonized by the alpha 2-antagonist yohimbine (1 microM) but not by the opioid antagonist naloxone (10 microM). These findings suggest that noradrenaline, probably released from the descending inhibitory system, reduces the release of glutamate from the capsaicin sensitive primary afferent terminals through alpha 2-adrenoceptors. PMID- 7792057 TI - Prenatal ethanol exposure alters neurotrophic activity in the developing rat hippocampus. AB - Extract made from hippocampus of rat pups exposed prenatally to an ethanol supplemented diet was found to contain more neurotrophic activity at postnatal day 21 than that from animals exposed to control diets, when quantified in a dorsal root ganglion bioassay. This apparent upregulation was specific to hippocampal extract (cerebellar and forebrain/midbrain extracts were also assessed), and to this age (P1, P7, P14 and P60 extracts were also tested). It was suggested that this upregulation may be indicative of, or secondary to, trauma resulting from fetal ethanol exposure. It is speculated that such departures from the normal developmental timetable could contribute to anomalies seen in the fetal alcohol syndrome. PMID- 7792059 TI - Expression of glutamate transporters in cultured glial cells. AB - Expression of mRNAs for glutamate transporter (GLT-1) and glutamate aspartate transporter (GLAST) was investigated in three different types of purified glial cells by the reverse transcriptase-polymerase chain reaction (RT-PCR). Cultured astrocytes, oligodendrocytes, and microglia expressed mRNAs for GLAST and GLT-1; mRNA for GLAST was expressed more prominently than that for GLT-1 in astrocytes. Oligodendrocytes and microglia expressed mRNAs for both GLT-1 and GLAST equally, but the expression in microglia was not prominent, suggesting glutamate uptake is not essential in microglia. In astrocytes cultured from different brain regions, GLAST mRNA was equally expressed. GLT-1 mRNA was also detected in these astrocytes, but the expression level was lower than that of GLAST. PMID- 7792060 TI - Bird viruses in multiple sclerosis: combination of viruses or Marek's alone? AB - This is a short report confirming recent articles that birds are very likely involved as vectors of the exogenous causative agent of multiple sclerosis (MS). It also critically reviews the most recent article (MacGregor, H. and Latiwonk, Q., Neurol. Res., 15 (1993) 391-394.) in which a high percentage of serums from MS patients reacted positively with Marek's antigen and it was accidentally discovered that Epstein-Barr virus antibodies also cross-react positively with Marek's antigen. This discovery might help explain the complex epidemiology of MS (an infectious mononucleosis infection would immunize a person against future mononucleosis and a Marek's infection). A table comparing the similarities between MS and Marek's is included. Other possible avian viral candidates are entertained plus the possibility of various viral combinations within a protective chlamydial plasmid including Marek's and avian retroviruses. PMID- 7792061 TI - The effect of cholinoceptor agonists and neurotoxins on the release of vasopressin in the rat in relation to the subunit composition of the cholinoceptor. AB - The effects of cholinoceptor agonists and neurotoxins on the release of vasopressin and oxytocin have been investigated in water-loaded rats under ethanol anaesthesia. Release of vasopressin was monitored by antidiuretic responses accompanied by increased urinary excretion of vasopressin. The rate of excretion of oxytocin-like radioimmunoreactivity was measured as an indicator of oxytocin release. Both nicotine and cytisine caused a preferential release of vasopressin. The release by nicotine was not inhibited by alpha- or neuronal bungarotoxin. Neosurugatoxin blocked the release by cytisine. Comparison with the effects of these agents on combinations of alpha and beta subunits expressed in oocytes suggests that the central cholinoceptors mediating release of vasopressin are similar to those at autonomic ganglia and may contain a beta 4 subunit. PMID- 7792062 TI - Motor cortex activity and predicting side of movement: neural network and dipole analysis of pre-movement magnetic fields. AB - Neuromagnetic fields were recorded from human subjects during the performance of left and right voluntary finger movements. Modeling of current dipole sources indicated symmetric activation of both motor cortices beginning 600 ms prior to movement onset. This activity became lateralized to the contralateral hemisphere 200-300 ms prior to movement onset, the period during which an artificial neural network showed increased ability to predict side of movement within single trials. The results describe the mechanism of lateralization of cortical brain activity preceding voluntary movement and provide further evidence of the involvement of ipsilateral motor cortex in unilateral movements. PMID- 7792064 TI - Light- and electron-microscopic localization of the glutamate receptor channel delta 2 subunit in the mouse Purkinje cell. AB - The localization of the glutamate receptor channel delta 2 subunit was investigated by immunohistochemistry. The delta 2-immunoreactivity was observed exclusively in the molecular layer of the cerebellar cortex. The electron microscopic analysis showed that the delta 2 subunit was localized in the dendritic spines of the Purkinje cells. The immunopositive spines often formed synaptic contacts with parallel fiber varicosities. As for the Purkinje cells ectopically localized in the cerebellar nuclei and brain stem, the dendritic shafts and cell bodies were strongly labeled. These ectopic Purkinje cells also formed asymmetrical synapses at the delta 2-immunopositive dendritic spines. Considering the specific localization of the delta 2 subunit in the postsynaptic site of the Purkinje cells, the subunit is suggested to be involved in the excitatory synaptic transmission in the cells, as a component of the glutamate receptor channel. PMID- 7792065 TI - Pancreatic polypeptide stimulates gastric motility through a vagal-dependent mechanism in rats. AB - The present study examined the influence of peripherally administered pancreatic polypeptide (PP) on vagal control of gastric motility. The jugular vein was cannulated in urethane-anesthetized rats and a strain gauge was sewn onto the antrum to monitor motility. Intravenous infusion of rat PP (2-200 pmol over 45 min) resulted in a dose-dependent increase in antral contraction amplitude. The motility response to i.v. PP was eliminated by pretreatment with atropine or bilateral vagotomy. In contrast to i.v. infusion, close intra-arterial infusion of PP into the gastric circulation had no effect on motility suggesting that PP does not act upon peripheral afferent terminals or directly within the stomach. These results support the hypothesis that circulating PP indirectly enhances gastric motility through a vagal cholinergic mechanism. PMID- 7792068 TI - Physician control of health care delivery in the managed care environment. AB - Managed care is a part of nearly every physician's practice. Physicians need not, however, lose control of their practices. By taking predetermined risks, physicians can maintain control over the quality of medical care, the manner in which that care is provided, their incomes, and their futures. PMID- 7792067 TI - Health care system reform and the changing physician-patient relationship. AB - The increasing management of medicine has meant an increasing intrusion into the physician-patient relationship. This has caused a shift in the balance of the basic principles of medical ethics and of the major aspects of the physician patient relationship. PMID- 7792063 TI - Spatial and temporal distribution of 7B2 in the pulmonary diffuse neuroendocrine system of the cat. AB - The postnatal developmental profile of the presence of 7B2 was studied immunocytochemically in the pulmonary diffuse neuroendocrine system of the cat. Labelling was found in neuroepithelial bodies (NEB) but not in solitary neuroendocrine cells. The identity of NEB was confirmed on adjacent serial sections by the immunostaining for protein gene product 9.5, a pan-neuroendocrine marker. The first 3 weeks after birth 7B2 stained NEB were most abundant with a subsequent decline thereafter. The positive correlation between the variation of 7B2 immunoreactivity and number of NEB suggests an important role for 7B2 in NEB. PMID- 7792066 TI - Efferent responses to twitch tests used in identifying human muscle afferents. AB - The response of a muscle afferent to the mechanical stimulus produced by a twitch contraction of the receptor-bearing muscle is an important test for differentiating between muscle spindle endings and Golgi tendon organs. The present study demonstrates that active alpha-motor axons can behave in a similar manner to spindle afferents, presumably responding not to the mechanical event per se, but reflexly to the change in afferent discharge created by the mechanical event. alpha-Motor axons were unequivocally identified during microneurography using spike-triggered averages of EMG. Caution is required when the twitch test is utilized to assist in the classification of muscle afferents during an intentional or unintentional voluntary contraction. PMID- 7792069 TI - The purposes, formation, and legal implications of PHOs. AB - In response to rapid changes in the health care delivery system, hospitals and physicians are exploring collaborative efforts. One of these efforts is the physician hospital organization (PHO). This article explores the purposes for forming PHOs, their actual formation, and related legal issues. PMID- 7792071 TI - Health care reformation and the need for tort reform. AB - Health care reform is changing the medical profession and the way physicians manage their patients, including reducing the incentive to practice defensive medicine. Conflicting pressures on physicians make this an ideal time for medical malpractice tort reform. PMID- 7792072 TI - Managed care and powerful networks result in state public utility commission. AB - This article focuses on why managed care, capitated payment, and the health alliances could lead to the formation of 15 major networks in New Jersey and require a Trenton-based health services commission. As a result, how physician services are organized in the state could undergo significant change. PMID- 7792070 TI - Regulation of medical practice in New Jersey. AB - The New Jersey state Board of Medical Examiners (BME) is responsible for protecting the public from impaired, unethical, or incompetent practitioners. This article discusses the structure and function of BME as well as several new BME initiatives. PMID- 7792073 TI - Feverfew: chemistry and biological activity. PMID- 7792074 TI - A morphological study of the retinal ganglion cells of the Afghan pika (Ochotona rufescens). AB - The distribution and morphology of the retinal ganglion cells was studied in a relative of the rabbit, the Afghan pika. The total number of retinal ganglion cells was approximately 170,000. The total number of optic nerve fibers was between 160,000 and 190,000, corresponding to the total number of retinal ganglion cells. Retinal ganglion cells were found to have a horizontal region of high-density. The maximum density was 5250 cells/mm2. This region was located in the central retina below the optic disc. This area contained numerous closely packed small ganglion cells, while the peripheral retina (especially in the dorsal periphery) contained large ganglion cells more loosely dispersed. The retinal ganglion cells labeled by horseradish peroxidase (HRP) were morphologically classified into three types based on dendritic length and ramification pattern. PMID- 7792075 TI - Straying phenomenon of migrating LHRH neurons and highly polysialylated NCAM in the chick embryo. AB - The present study on unilaterally incompletely placodectomized chick embryos revealed that arrival of migrating LHRH neurons into the forebrain area is dependent on the presence of a central projection of the olfactory nerve. When a fragment of the lateral and medial olfactory epithelium was spared the damage, a small number of LHRH-ir cells were found to migrate into the forebrain along a thin NCAM-H-expressing fiber bundle of the olfactory nerve. In embryos with large lesions which destroyed the lateral olfactory epithelium, the poorly developed NCAM-H-positive olfactory nerve fibers were arrested where they meet the NCAM positive medial nasal branch of the ophthalmic nerve and frequently fused with this branch fiber bundle. In these embryos, no LHRH-ir cells were detected in the forebrain area. They were deviated from their regular migratory course to the NCAM-H-positive medial nasal branch fiber bundle. This straying phenomenon indicates that some structural support is apparently needed for the migration of LHRH-ir cells, but their migratory route is not completely programmed in their precursor cells in the olfactory placode. In cultures of placodal tissues, the coexistence of migrating LHRH-ir cells with NCAM-H-expressing neural elements was always confirmed. It is suggested therefore that not only the structural support for the migration but also the interaction between LHRH-ir cells and NCAM-H expressing neural elements is a prerequisite for successful LHRH neuronal migration. PMID- 7792076 TI - Rapid eye movement sleep deprivation decreases membrane fluidity in the rat brain. AB - In this study we examined the effects of rapid eye movement sleep (REMS) deprivation on synaptosomal and microsomal membrane fluidity by studying 1,6 diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization in control as well as REMS-deprived rats. The flower pot technique was used to perform 24, 48 and 96 h REMS deprivation. Suitable control experiments were carried out to rule out the nonspecific effects. The results showed that DPH fluorescence polarization increased both in the microsome as well as in the synaptosome in REMS-deprived animals, except in the cerebellum, indicating that there was a generalized decrease in membrane fluidity in the rat brain. The alterations in membrane fluidity returned to baseline upon recovery from REMS deprivation. Control experiments suggested that the alterations were primarily caused by REMS deprivation and not due to nonspecific effects. This finding supports REMS deprivation induced other changes reported earlier. This increase in membrane rigidity could be at least one of the possibilities for REMS loss induced alterations in physiological phenomena including membrane bound enzyme activities and receptor densities. PMID- 7792077 TI - Cyclosporin A prevents ischemia-induced reduction of muscarinic acetylcholine receptors with suppression of microglial activation in gerbil hippocampus. AB - We previously reported the late onset reduction of muscarinic acetylcholine receptors (LORMAR) which begins 7 days after a 5-min period of experimentally induced forebrain ischemia in the gerbil hippocampus. This study demonstrated that post-ischemic administration of cyclosporin A (CsA) reduced LORMAR 10 days after 5 min of forebrain ischemia in the gerbil hippocampus, suggesting that immunosuppression by CsA may reduce damage to the cholinergic system after ischemia. Microglia positive for HLA-DR class II antigen which presented in the hippocampal CA1 area, the region most vulnerable to ischemia, were also reduced by CsA. CsA may suppress microglial activation especially with regard to the antigen-presenting function, and LORMAR may be attenuated by this modulation of microglial function. PMID- 7792078 TI - A sodium- and energy-dependent glucose transporter with similarities to SGLT1-2 is expressed in bovine cortical vessels. AB - In order to investigate glucose transport at the blood-brain barrier (BBB), glucose transport properties were studied pharmacologically with a novel model system of inverted bovine brain cortical arteries. These vessels displayed glucose transport characteristics of facilitative glucose transporters (GLUT1-5) and of sodium- and energy-dependent glucose transporters (SGLT1-2). So far, glucose transport in the central nervous system (CNS) has only been shown to be achieved by facilitative transporters, in particular by GLUT1 at the blood-brain barrier and in glial cells and by GLUT3 in a subset of neurons. We report here that a SGLT-like transporter might partake in glucose transport at the bovine BBB, as indicated by immunocytochemical analysis and by Western immunoblot analysis of cultured bovine brain endothelial cells. A RNA protection assay revealed the presence of a SGLT-like gene fragment in rabbit cortex. PMID- 7792080 TI - Functional roles of the superior laryngeal nerve afferents in electrically induced vocalization in anesthetized cats. AB - Our purpose was to elucidate the functional roles of the laryngeal afferents in controlling vocalization. We investigated the effects of laryngeal deafferentation (sectioning the internal branch of the superior laryngeal nerve (ISLN)) on respiration and voice quality during electrically-induced vocalization in twelve ketamine anesthetized cats. Co-ordinated vocal activity was obtained by electrical stimulation to the pontine call site. After the bilateral ISLN section, the respiratory, expiratory and inspiratory durations during induced vocalization became 0.56 +/- 0.15, 0.44 +/- 0.12 and 0.67 +/- 0.19 (mean +/- S.D., n = 9) times, respectively, compared with those before the ISLN section. A decrease in respiratory duration was also observed when local anesthetics were applied to the laryngeal mucosa. The laryngeal deafferentation increased the degree of hoarseness with a decrease in the fundamental frequency. Since the laryngeal deafferentation caused a decrease in the intralaryngeal adductor activities, it was suspected that the voice quality change was partly caused by the reduction in adductor activities. It was thus concluded that feedback via laryngeal afferents plays an important role in controlling vocalization. PMID- 7792079 TI - Immunohistochemical localization of protein phosphatase isoforms in the rat cerebellum. AB - Protein phosphatase isoforms, PP1 gamma 1, PP1 delta, PP1 alpha and PP2A (alpha and/or beta), were immunohistochemically localized in the rat cerebellum. Purkinje cell perikarya, dendrites and spines were very PP1 gamma 1 immunoreactive. PP1 delta and PP1 alpha were perinuclear in all neurons, PP1 alpha also revealed a new cell type and PP2A was homogeneous in Purkinje cell soma and large dendrites. PP1 gamma 1 seems to be dominant for dephosphorylation at the dendritic synapses of Purkinje cells. PMID- 7792082 TI - Conductivity ratios of the scalp-skull-brain head model in estimating equivalent dipole sources in human brain. AB - The dipole tracing (DT) method estimates the position and vector dipole moment of an equivalent current dipole by minimizing the mean squared error of the dipole potentials at the surface electrode positions. In the scalp-skull-brain/DT (SSB/DT) method, which we have developed, the head model consists of three compartments of uniform conductors corresponding to the scalp, skull and brain. The accuracy of the calculations are mainly dependent on the ratios of the conductivities of the three compartments. The best result was obtained with the conductivity ratios of 1:1/80:1 for the scalp, skull and brain compartments, respectively. PMID- 7792081 TI - Conditioned taste aversion in rats with excitotoxic brain lesions. AB - Conditioned taste aversion (CTA) is well known to be a robust and long-lasting learning after a single conditioned stimulus (CS) (taste)--unconditioned stimulus (US) (malaise) pairing. The neural mechanisms of this taste aversion learning still remain to be resolved. To elucidate the basic brain mechanisms of the taste aversion learning, we examined the effects of lesions of various sites of the rat brain on the acquisition and retention of CTAs. Confined brain lesions were made by injections of a small amount of excitotoxic drug, ibotenic acid. CTAs were established to saccharin (CS) by pairing its ingestion with an i.p. injection of LiCl (US). Rats lacking the parabrachial nucleus (PBN) almost completely failed to acquire CTAs. The second most effective lesion was in the medial thalamus including the parvocellular part of the ventral posteromedial nucleus of the thalamus (VPMpc) and the midline part, followed by the damage of the lateral nuclear group of the amygdala including the basolateral amygdaloid nucleus. Lesions of the gustatory cortex (GC) and hippocampus induced moderate effects, but lesions in the other subnuclei of the amygdala, such as the medial and central amygdaloid nuclei, entorhinal cortex, lateral hypothalamic area, and ventromedial hypothalamic nucleus induced slight or no effects. On the other hand, paired lesions among the amygdala, medial thalamus and GC caused severe impairment of CTAs; in particular, lesions of amygdala and VPMpc completely disrupted acquisition of CTAs. These results suggest that the PBN, medial thalamus and the lateral nuclear group of the amygdala play an essential role in the formation of taste aversion learning. PMID- 7792083 TI - Diametrically opposite effects of estrogen on the excitability of female rat medial and lateral preoptic neurons with axons to the midbrain locomotor region. AB - Electrical stimulation of the midbrain locomotor region (MLR) in 76 ovariectomized, urethan-anesthetized female rats elicited antidromic action potentials in 252 preoptic neurons. Thresholds and refractory periods for the activation ranged from 60 to 1550 microA and 1.3 to 5.0 ms, respectively. The probability distribution for the peak-to-peak amplitude (2-14 mV) or the overall duration (0.7-4.4 ms) was bell-shaped, whereas that for the latency (1.8-33.5 ms) was distinctively bimodal with a division at 12.0 ms. Two groups of preoptic neurons of a similar soma size therefore project to the MLR presumably via different routes. In 121 neurons with latencies < or = 12.0 ms, estrogen lowered the antidromic activation thresholds (nested analysis of variance, P < 0.02), but 131 neurons with latencies > 12.0 ms had their thresholds increased (P < 0.005) and refractory periods prolonged (P < 0.02) by estrogen. Even though both overlapped in part, many potentials with the shorter latencies were recorded from the medial part of the lateral preoptic area (mLPO), lateral to the recording sites of the longer-latency potentials in the medial preoptic area (MPO). The observed antagonistic effects of estrogen on the two groups of preoptic neurons with axons to the MLR may contribute to increased locomotor activity in female rats in estrus. PMID- 7792084 TI - Discrete acetylcholine release from neuroblastoma or hybrid cells overexpressing choline acetyltransferase into the neuromuscular synaptic cleft. AB - Neuroblastoma (clones NS-20Y, N1E-115, and Neuro2A) and neuroblastoma x glioma hybrid (NG108-15) cells were transfected with mouse choline acetyltransferase (ChAT) complementary DNA (cDNA) or vector DNA alone and stably transformed cell lines were established to examine their ability to secrete acetylcholine (ACh). Membrane potentials were recorded from either presynaptic neuroblastoma and hybrid cells or postsynaptic myotubes in co-culture. After transformation with ChAT, synapses were formed and miniature end-plate potentials (MEPPs) were recorded in myotubes co-cultured with Neuro2A and N1E-115 cells, while parental and mock-transfected control cells totally lacked this ability. The rate of synapse formation and/or MEPP frequency was higher in transformed NG108-15 hybrid and NS-20Y cells than that in the control cells. Action potentials of NS-20Y, Neuro2A or NG108-15 cells overexpressing ChAT were able to evoke end-plate potentials in myotubes, though the average quantum content of these cells was 0.04-0.14, which is as low as the control value. The results show that increased concentrations of ACh by ChAT cDNA transfection reveal a masked property in vesicular ACh release from Neuro2A and N1E-115 cells with no endogenous ChAT activity, or modify their secretory capacity upwardly from NG108-15 and NS-20Y cells with endogenous activity. PMID- 7792086 TI - Liability reform: organized medicine scores big! PMID- 7792087 TI - PPHP founder talks of medicine's future. Interview by Elaine S. Herrmann and Maria T. Montesano. AB - The Pennsylvania Medical Society's Board of Trustees in March approved a recommendation to fully support and endorse the goals of the Pennsylvania Physician Healthcare Plan, Inc. Also known as PPHP, the plan aims to be the commonwealth's first statewide, physician-owned managed care organization. Gary C. Brown, MD, a Wyndmoor ophthalmologist, is the founder and driving force of PPHP. Shortly after the board action, Dr. Brown spoke with us about the concept of physician control, his involvement with PPHP, and the organization's chances of success. PMID- 7792085 TI - Distribution of the calcium binding proteins, calbindin D-28K and parvalbumin, in the subicular complex of the adult mouse. AB - The immunohistochemical localizations of two specific calcium binding proteins, calbindin D-28K (calbindin) and parvalbumin (PV) were examined in the subicular complex, that is, the subiculum, presubiculum, and parasubiculum, of the adult mouse and were compared in detail with staining pattern of the acetylcholinesterase (AChE) histochemistry. The calbindin immunoreactivity exhibited a conspicuous regional and laminar pattern of distribution, which somewhat resembled the AChE staining pattern but was apparently different from the latter in various points. The PV immunoreactivity also exhibited a characteristic regional difference, although less prominent. The subiculum could be divided into two subregions, intensely calbindin-immunoreactive (calbindin-IR) and AChE stained proximal subiculum and only faintly calbindin-IR and AChE stained distal subiculum. In the subiculum most of calbindin-IR neurons were pyramidal cells which were clustered in the superficial half of the cell layer in the proximal subiculum and appeared to be segregated from calbindin negative pyramidal cells located in the distal subiculum and in the basal part of the proximal subiculum. In the presubiculum calbindin-IR neurons were clustered in layer 2, most of which were supposed to be presubicular pyramidal cells. In the parasubiculum, the overall immunostaining pattern of PV and calbindin were somewhat complementary. In the transition area calbindin-IR neurons were clustered but few PV-IR neurons were located, and thus the distribution of immunoreactive neuronal somata was apparently different from the adjacent parts of the parasubiculum, indicating that the transition area might be a separate entity. In addition to calbindin-IR presumable principal neurons, calbindin-IR and PV-IR nonpyramidal cells were scattered throughout the subicular complex. Furthermore, these two calcium binding proteins were colocalized in some nonpyramidal cells in the subicular complex. The present study revealed some new aspects of the areal and laminar organization of the subicular complex, which had not been shown by previous classical purely morphological approaches. PMID- 7792088 TI - Physician leverage: your strength is in your unity. PMID- 7792089 TI - Patients' medical records: whose business is it anyway? AB - Physicians receive many requests for medical records information: Attorneys request medical records information for court cases; colleagues request information which may assist with consultations or in the medical care of individual patients; insurers request information with respect to necessity or appropriateness of care. However, none of these scenarios prompt as many telephone calls for advice to the Office of General Counsel at State Society headquarters as does the call or letter from a patient requesting a copy of his or her medical record. PMID- 7792090 TI - Veterans' health care: lessons for care planners. AB - Integrated care is a popular trend in today's health care marketplace. In this article, the former Pennsylvania secretary of health, now chief of staff at the Lebanon VA Medical Center, H. Arnold Muller, MD, describes a model integrated health care system which has been operating for almost 50 years--the medical centers run by the U.S. Department of Veterans Affairs. PMID- 7792091 TI - Ignore mergermania; find your niche. Downsizing: an alternate solution to managed care woes. PMID- 7792092 TI - New therapeutic agents marketed in 1994. AB - A total of 21 therapeutic agents reached the U.S. market for the first time in 1994, representing a continuation of the decline from the record number of 31 new therapeutic agents which were marketed in 1991. This review of the therapeutic agents first marketed in 1994 considers their most important properties. When additional information is needed, more comprehensive references and the product literature should be consulted. PMID- 7792094 TI - Good communication: the best defense against litigation. PMID- 7792095 TI - Is emergency medicine emergency medicine? PMID- 7792093 TI - KePRO south: a source of pride. PMID- 7792096 TI - Influence of humoral immunity on leukotriene B4 production by neutrophils in response to Trichomonas vaginalis stimulation. AB - Neutrophils are the predominant inflammatory cells found in vaginal discharges from patients with Trichomonas vaginalis infection. In this study, we investigated the effect of humoral immunity on leukotriene B4 (LTB4) generation by neutrophils in the inflammatory response of vaginal trichomoniasis. As quantitated by a radioimmunoassay, no release of LTB4 was detected from neutrophils (5 x 10(6)/ml) interacted with trichomonads (1 x 10(6)/ml). However, specific immunoglobulin G(IgG) but not F(ab')2, at a titre of 1:256 directed against T. vaginalis, augmented LTB4 production (1.4 +/- 0.4 ng/ml, n = 5) by neutrophils, suggesting that this enhancement is Fc gamma receptor-mediated. Moreover, addition of the specific IgG (1 mg/ml) to C2-deficient serum or Factor B-deficient serum, but not C5-deficient serum, significantly increased LTB4 production by neutrophils in response to trichomonad stimulation. This indicates that the complement common pathway activation is crucial for the amplification of host defence mechanisms against T. vaginalis. An LTB4 receptor antagonist, SC 41930, completely abolished neutrophil chemotactic activity induced by LTB4. Taken together, these results indicate that humoral immunity could promote the interaction of neutrophils with T. vaginalis and augment the inflammatory response through the amplification of LTB4 production. PMID- 7792097 TI - Relationship between granulocyte macrophage-colony stimulating factor, tumour necrosis factor-alpha and Trypanosoma cruzi infection of murine macrophages. AB - Gamma interferon (IFN-gamma)-activated macrophages control Trypanosoma cruzi infection via nitric oxide (NO), recently recognized as a major effector molecule. Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent cytokine secreted by macrophages and many other cells. It induces the production of tumour necrosis factor alpha (TNF-alpha), another cytokine also secreted by macrophages and involved in the control of T. cruzi infection. However, no data are available on the relationship between GM-CSF, TNF-alpha and NO produced by macrophages activated by IFN-gamma and infected with T. cruzi. To highlight this relationship, mouse peritoneal macrophages (MPM) and two c-myc retrovirus-induced macrophage cell lines (9.1.1 and BMM8), respectively characterized by a constitutive and an inducible production of GM-CSF, were activated with IFN-gamma and/or GM-CSF and infected with T. cruzi. Our results indicate that T. cruzi upregulates GM-CSF release from MPM and from the two macrophage cell lines, activated (or not) by IFN-gamma. A high autocrine production of GM-CSF or an exogenous supply of GM-CSF is correlated with an enhanced release of TNF-alpha and NO, inducing an improved control of T. cruzi infection by IFN-gamma-activated MPM. PMID- 7792098 TI - Suppressor macrophages in Trypanosoma brucei infection: nitric oxide is related to both suppressive activity and lifespan in vivo. AB - African trypanosome infections cause immunosuppression in both experimental rodent and natural hosts. One characteristic of this is an eliciting of suppressor macrophages which results in an unresponsiveness in lymphocytes. Macrophages from Trypanosoma brucei-infected mice have previously been shown to produce high levels of nitric oxide (NO). Using model systems based on in vivo macrophage transfer and drug cure, we have sought to determine the relationship between NO and suppressed lymphocyte responses. Peritoneal macrophages from T. brucei-infected mice inhibited the Concanavalin A (Con-A) response of spleen cells from syngeneic recipients 3-4 days after transfer in vivo due to the activity of suppressor macrophages. When macrophage NO synthesis was inhibited either in vitro or in vivo the suppressive effects were partially abrogated. These data provide evidence of a role for NO in mediating immunosuppression during murine T. brucei infection. Suppression in spleens of mice receiving suppressor macrophages was transient, with total recovery of spleen cell mitogen responses six days after transfer. Suppression and recovery was found to coincide with the presence or absence (respectively) of donor macrophages in recipient spleens. When T. brucei-infected mice were treated with a curative dose of a trypanocide there followed a recovery of lymphocyte responsiveness after a period of 4-5 days, and this directly correlated with a reduction of macrophage NO synthesis to control levels both in vivo and in vitro. The apparent loss of suppressor macrophage activity after 4-6 days in both drug cured animals and recipients of macrophage transfer was shown to be due to NO-mediated apoptosis of these cells. PMID- 7792099 TI - Induction of CD4+ and CD8+ T cell responses in efferent lymph responding to Toxoplasma gondii infection: analysis of phenotype and function. AB - The kinetics of induction of T cell responses were examined in efferent lymph from a node draining the site of a primary inoculation of Toxoplasma gondii. The numbers of T cells increased after infection, due initially to an expansion of the CD4+ T cell population followed by an increase in the number of CD8+ T cells which coincided with the peak lymphoblast response. Proliferative responses of CD4+ T cells to T. gondii antigen were detectable from day six after infection and immune efferent lymph cells inhibited the intracellular multiplication of T. gondii in vitro. Optimum inhibition was achieved using CD8+ T cells restimulated in vitro, and the effector function appeared to be directed preferentially against the autologous rather than the allogeneic infected target cell. The results provide unique information on the induction of immune responses to T. gondii in vivo and provide evidence that both CD4+ and CD8+ T cells are necessary for the development of protective immunity induced by the S48 strain of T. gondii which is used as a live vaccine in sheep. PMID- 7792101 TI - From a child's fable to a moral for nursing. PMID- 7792100 TI - The role of CD4+ and CD8+ T cells in protective immunity to the murine nematode parasite Trichuris muris. AB - The role of CD4+ and CD8+ T cells in protective immunity to Trichuris muris was studied in CD4+ or CD8+ or both CD4+ and CD8+ T cell-depleted BALB/c mice. To assess in vivo depletion of T-cell subsets, CD4+ and CD8+ T cells in the Peyer's patches, the mesenteric lymph nodes (MLN), and the spleens of mice treated with T cell-specific monoclonal antibodies (MoAbs) were analysed by FACS. CD4+ T cells were selectively depleted in mice injected with anti-CD4 MoAb i.p. and injection of anti-CD8 MoAb resulted in selective depletion of CD8+ T cells. The expulsion of T. muris was inhibited in CD4+ T cell-depleted mice and numerous worms were detected in the large intestine on days 14 and 21 after infection, although no suppression of protective immunity to T. muris was observed in CD8+ T cell depleted mice. Moreover, there was no difference in suppression of protective immunity to T. muris between CD4+ T cell-depleted and both CD4+ and CD8+ T cells play a central role in protective immunity to T. muris infection. PMID- 7792102 TI - Assessing acute abdominal pain in adolescent females. AB - The possible causes of acute abdominal pain in the adolescent female are varied and numerous. Some problems are self-limiting, while others can be life threatening. Etiologies include, but are not limited to, gastrointestinal, urinary, gynecologic, and psychosocial problems. Assessment requires taking an accurate history quickly, and includes assessing the characteristics of the pain, any associated symptoms, and the overall physical and psychosocial health status of the adolescent. Physical assessment begins with observing how the adolescent presents herself. Although the abdomen is the focus of the examination, the general examination should not be ignored. Laboratory and radiologic testing logically follow, yet in the case of acute abdominal pain, greater reliance is placed in the symptoms and signs. PMID- 7792103 TI - Female adolescent contraception. AB - Numerous clinical challenges confront care providers in caring for adolescents regarding contraception and sexual health issues. Strong communication skills are an integral factor in dealing with the sexually active teen. The most common contraceptive options for adolescents include Norplant, Depo-Provera, oral contraception, and condoms. Providing contraceptive care for adolescents requires knowledge of these methods, including the new FDA guidelines that standardize instructions for oral contraceptive use. Nursing responsibilities include counseling the adolescent regarding the risks of sexual activity with multiple partners, exposure to HIV, STDS, and the correct use of condoms. Educational efforts should focus on improving adolescent communication skills and encouraging discussion by sexual partners about the issue of condom use. PMID- 7792104 TI - Menstrual dysfunction in athletes: assessment and treatment. AB - The reported incidence of exercise induced menstrual dysfunction varies among adolescent athletes from 12% to 66%. Women who experience amenorrhea associated with exercise are at risk for irretrievable bone mineral density loss and increased rate of stress fractures. Nurses should provide information to parents, coaches, and athletes about changes in exercise intensity and frequency, dietary modifications, and estrogen and progesterone replacement therapy to minimize the sequelae of exercise induced menstrual dysfunction. PMID- 7792106 TI - Parental perspectives related to decision-making and neonatal death. AB - With the advent of many new technologies, decision-making about the care of critically ill neonates represents one of the primary ethical arenas in health care today. Professionals and parents are forced to make decisions about when, how, and if critically ill neonates die. This qualitative study, based on interviews with a very small, convenience sample of parents, begins to explore the parental perspective about ethical decision-making regarding critically ill neonates by describing their personal experiences as they faced the reality or possibility of their babies' deaths. PMID- 7792105 TI - Social support and coping in young adolescents with cancer. AB - The social support networks and coping mechanisms of adolescents with cancer were assessed in this study. Twenty 10 to 16-year-olds completed the Norbeck Social Support Questionnaire (NSSQ) and the Adolescent Coping Orientation for Problem Experience (A-COPE). Social support networks of youths with cancer were found to include the following: parents, siblings, other relatives, friends, other nonprofessionals, and professionals. Males and females listed a similar number of persons in their personal network (6.5 and 7.0 respectively). Overall, adolescents reported a high amount of perceived functional support (affect, affirmation, aid). They also reported being very satisfied with the general support and support specific for their cancer from different groups of people. Although the sample was limited in size, adolescents in this study reported using a number of coping behaviors that are similar to those reported in the normative data. Moderate positive correlations were found between functional support and specific coping patterns. Significant moderate negative correlations were found between the length of illness and specific coping patterns. Results of the study are discussed and recommendations for future research are made. Nursing implications are discussed as they pertain to clinical practice. PMID- 7792109 TI - New books related to the care of children. PMID- 7792107 TI - Family experiences when a child is HIV-positive: reports of natural and foster parents. AB - The purpose of this exploratory study was to examine issues reported by natural and foster parents when caring for a child 3 years of age or younger with vertically transmitted HIV-disease. Issues common to both groups, and specific to the natural and foster parents were explored. The issues discussed by the natural mothers included guilt, their relationship with their infected child, and the effects of their HIV infection on their family. Issues discussed by foster mothers included their decision to foster a HIV-positive child, characteristics of their HIV- positive foster children, fears of transmission, and the effect of the HIV-positive foster child(ren) on their natural family. Issues common to both sets of mothers include disclosure, support, preparation for the HIV-positive child's death, and life in general. The experiences of these families are important to describe in order for pediatric nurses to give accurate, sensitive, and culturally appropriate care. PMID- 7792108 TI - When values conflict with obligations: safeguards for nurses. AB - Increasingly, nurses are being confronted with clinical situations that challenge their personal and professional integrity. For integrity to be preserved, safeguards must be developed and an environment that supports ethical practice fostered. Standards such as those promulgated by the JCAHO provide an important opportunity for nurses to create mechanisms to assure that diverse religious, cultural, and ethical beliefs of nurses are respected and upheld. PMID- 7792110 TI - Incubator noise: a method to decrease decibels. AB - PURPOSE: To examine the effect of covering the incubator on environmental noise levels inside the incubator. METHOD: Noise level measurements were taken to measure noise outside the incubators, inside the uncovered incubators, and inside covered incubators of 24 premature infants. The sound levels and differences in patient care equipment were analyzed by means, t-tests, and ANOVA. FINDINGS: Significant differences were found between the covered and uncovered incubators' sound level readings. Covered incubators had lower noise level readings. CONCLUSION: Covering incubators is one method to decrease environmental noise in the NICU. PMID- 7792112 TI - Antiretroviral therapy in infants and children with HIV. PMID- 7792111 TI - Child health issues in the 104th Congress. PMID- 7792113 TI - Teasing: who says names can never hurt you? AB - Although teasing is a common behavior of children, it does not occur without consequences in children. Children at particular risk are those with differing beliefs and feelings, distinctive personality traits, or obvious physical differences from that of the group norm. In these children, teasing can have deleterious effects on their psychological well-being. Strategies to use for assessment of and intervention with high-risk children are presented. PMID- 7792114 TI - Resources for family-centered care: an annotated bibliography. AB - Understanding and implementing family-centered care becomes easier as nurses are exposed to both the concept and examples of the concept in practice. An annotated bibliography of articles, books, films, training materials, and newsletters will be useful to individual nurses, nurse-educators, and nurse administrators. PMID- 7792115 TI - What is your assessment? Otitis media with effusion. PMID- 7792116 TI - Gender differences in asthma. PMID- 7792117 TI - The Yentl syndrome in childhood asthma: risk factors for undertreatment in Swiss children. AB - Recent prevalence data for childhood asthma in Switzerland suggest a substantial underdiagnosis which seems to be more pronounced in girls. We further analysed our data trying to specify risk factors for underdiagnosis and undertreatment. Our special interest was focused on female sex as there is evidence for a sex dependent diagnosis and treatment of chronic disease in adults, called the Yentl syndrome. The data are derived from a parent completed questionnaire survey of a stratified cluster sample of schoolchildren aged 7, 12, and 15 years. Besides the 12 months prevalence of asthma symptoms and bronchodilator treatment, the lifetime prevalence of an asthma diagnosis was noted. With a response rate of 97%, a total of 4353 completed questionnaires were analysed. While age was not associated with undertreatment (except for exercise-induced symptoms in adolescents), the lack of a formal diagnosis of asthma and atypical asthma symptoms other than wheeze such as chronic night cough were confirmed as significant risk factors for undertreatment. Of all boys reporting asthma symptoms 31% received bronchodilator treatment compared with only 15% of the symptom-reporting girls (P < 0.001). For all particular asthma-related symptoms (except wheeze), significantly more boys than girls (approximately double) received treatment. The physiological and psychological bases for these findings are discussed and suggest that gender is an important risk factor for underdiagnosis and undertreatment of asthma. Our research indicates that the Yentl syndrome may exist for childhood asthma. PMID- 7792118 TI - Prevalence of respiratory symptoms in Swiss children: is bronchial asthma really more prevalent in boys? AB - Precise epidemiological data for the prevalence of childhood asthma were lacking for Switzerland until recently. In 1990 we performed a stratified cluster sampling of schoolchildren (aged 7, 12, and 15 years), using a parent completed questionnaire to obtain data for the 12 months prevalence of asthma symptoms and the lifetime prevalence of asthma diagnosis. A response rate of 97.5% enabled us to analyse 4,353 completed questionnaires. The prevalence of any asthma symptom during the last 12 months was 17.5% while only 4.8% of the children reported the diagnostic label "asthma". The 12 months prevalence of chronic night cough was 12% and is comparable to other European data. Wheeze (5.9%) was reported less often in Switzerland than in England. At the age of 7 years asthma symptoms such as wheeze, morning tightness, and allergen-induced symptoms were reported more often in boys than in girls; at the age of 12 and 15 the male preponderance was no more evident. For all asthma symptoms the male-female ratio decreased with increasing age of the children, while independently of age twice as many boys than girls reported the diagnostic label "asthma." We conclude that asthma symptom prevalence in Swiss schoolchildren is within the lower range of European data. Chronic night cough might be a more appropriate variable to compare prevalence rates between regions with different cultural and linguistic backgrounds that the symptom of wheeze. Evidence exists for a substantial underdiagnosis of bronchial asthma in Swiss children, especially in girls. Further evaluation is needed to define risk factors for underdiagnosis and the associated risk for undertreatment. PMID- 7792120 TI - Preservation of pulmonary function in the ventilated neonatal piglet with normal lungs. AB - Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm H2O PEEP (2PEEP group). We further hypothesized that an intermittent lung inflation procedure consisting of 15 out of 60 min of increasing lung distention (4, 8, 12 cm H2O PEEP), with the remaining 45 min at 2 cm H2O PEEP (Inflation group) would prevent this deterioration in lung function, similar to piglets mechanically ventilated continuously at 6 cm H2O PEEP (6PEEP). Results indicate that 2PEEP piglets experienced progressive deterioration in lung function, including dynamic lung compliance (-42%) and lung resistance (+55%). In contrast, inflation piglets and 6PEEP piglets had no deterioration in lung function. Hemodynamics were similar between groups, although they were the most stable in the 6PEEP group. Histopathological changes were not significantly different. We conclude that (1) prolonged mechanical ventilation at 2 cm H2O PEEP in neonatal piglets resulted in progressive deterioration in pulmonary function, (2) intermittent lung inflation or continuous 6 cm H2O PEEP prevented deterioration, and (3) functional changes occurred without changes in histopathology. Lung inflation strategies other than PEEP can be used to prevent deterioration in lung function which accompanies prolonged mechanical ventilation in anesthetized nonspontaneously breathing piglets with normal lungs. PMID- 7792121 TI - Spontaneous pneumothorax as the first manifestation of Ewing's sarcoma. PMID- 7792122 TI - Cystoplasty for treatment of a congenital lung cyst. PMID- 7792119 TI - Validation of the phase angle technique as an objective measure of upper airway obstruction. AB - Thoraco-abdominal asynchrony (TAA) during upper airway obstruction (UAO) in small children can be documented by phase angle analysis of the Lissajous figure from the output of a noncalibrated respiratory inductance plethysmograph. Phase angle measurements have not been related to levels of inspiratory resistance, nor to the effect of breathing a 79% helium-21% oxygen mixture (heliox) during inspiratory resistance. We examined the effects of graded inspiratory loading (5 1000 cm H2O/L/sec) on TAA as measured by phase angle in 10 male, anesthetized, and intubated Rhesus monkeys, breathing room air and heliox. Phase angles increased with inspiratory loading from a baseline value of 22 +/- 3 degrees to 165 +/- 8 degrees at 1,000 cm H2O/L/sec resistance and correlated significantly with the level of inspiratory loading (r = 0.82). End-tidal carbon dioxide PETCO2 increased from 39 +/- 1 to 49 +/- 3 mm Hg at the highest load, but correlated only weakly with phase angle measurements (r = 0.60) and the level of inspiratory loading (r = 0.56). By changing to heliox breathing at the highest tolerated resistance, PETCO2 dropped significantly from 49 +/- 3 to 40.5 +/- 4 mmHg (P < 0.001) with no significant change in phase angles: 169 +/- 13 degrees and 165 +/- 8 degrees, respectively (P > 0.05). We conclude that heliox therapy for acute alveolar hypoventilation during UAO improves ventilation, but does not decrease TAA at high inspiratory resistance. Continuous monitoring of the relative changes in phase angles is useful to observe the severity of UAO in the early stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792123 TI - Primary lung abscess in infancy. PMID- 7792124 TI - The surface monolayer theory does not explain surfactant function in vivo. PMID- 7792125 TI - Clinical experience with cefpodoxime proxetil in acute otitis media. AB - Although it varies from country to country, there is a worrying worldwide increase in antibiotic resistance among pathogens causing otitis. This has led to a search for therapeutic alternatives to the reference treatment, which is still amoxicillin in many countries. Cefpodoxime proxetil is one such alternative. Six comparative randomized trials of cefpodoxime proxetil in childhood acute otitis media have been published or presented at international conferences. They involved a total of 1188 patients, 658 of whom received cefpodoxime proxetil and 530 of whom received the comparator drug (amoxicillin/clavulanic acid in 3 trials, cefaclor in 1, and cefixime in 2); duration of treatment varied from 5 days for cefpodoxime proxetil to 10 days for amoxicillin/clavulanic acid, and the age of the children included ranged from 2 months to 12 years. The clinical efficacy of cefpodoxime proxetil was at least equivalent to that of the comparators in 4 trials and significantly better in 2 trials. Firstly, in one study vs. amoxicillin/clavulanic acid, the superiority of cefpodoxime proxetil (8 mg/kg/day twice daily) in terms of healing at the end of treatment and in terms of the number of normal tympanograms at the follow-up visit was shown. Secondly, in a study performed by our group, vs. cefixime, cefpodoxime proxetil (8 mg/kg/day twice daily) showed a better healing rate at the end of treatment in febrile and painful acute otitis media. The microbiologic and pharmacokinetic data show that cefpodoxime proxetil is one of the most active compounds against Haemophilus influenzae and Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792126 TI - Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group. AB - Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year. Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections. However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins. The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections. In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years. Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day). The duration of treatment was 10 days. Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients. Pathogens isolated from 59 cases included H. influenzae (47.5%), S. pneumoniae (23.7%), M. catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%). Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved). The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792128 TI - Do we still need new oral antibiotics for community-acquired infections in pediatrics? Introduction. PMID- 7792127 TI - Otitis media complications and treatment failures: implications of pneumococcal resistance. AB - Classic complications of untreated otitis media include meningitis, lateral sinus thrombosis and chronic suppurative otitis media. In the past, in countries where otitis media is usually treated, complications have been rare, because of the good activity of almost all orally administered antibiotics against the most common cause of complications, Streptococcus pneumoniae. Treatment failures were usually caused by beta-lactamase-producing nontypable Haemophilus influenzae or by Moraxella (Branhamella) catarrhalis and were rarely associated with serious systemic infections. With the advent of multidrug-resistant pneumococci, however, serious and fatal infections can occur in the face of our most potent antimicrobial agents. The consequences of the emergence of multidrug-resistant pneumococci are likely to include more persistent purulent otitis media, increased usage of broad-spectrum antibiotics, an increase in surgical treatment rates for otitis media and, eventually, an increase in suppurative complications of otitis media. Medical treatment failures probably already surpass eustachian tube dysfunction as the most common reason for tympanostomy tube insertion. Multidrug-resistant pneumococci may be expected to change the way in which primary and secondary care is currently administered. PMID- 7792129 TI - Pharyngitis/tonsillitis: European and United States experience with cefpodoxime proxetil. AB - Most authorities continue to recommend penicillin as the treatment of choice for group A streptococcal pharyngitis. If penicillin is used, 10 days of treatment are necessary to achieve a clinical and bacteriologic cure. The usually recommended penicillin V dose is 250 mg (400,000 IU) three times daily. Twice daily dosing is acceptable to some authorities if compliance is good. However, oral penicillin fails to eradicate group A streptococci from the pharynx in up to 17% of cases; in some studies 30% failure rates have been reported. Several European and United States studies indicate that a variety of oral cephalosporins, when used for 10 days, are significantly superior to penicillin V in eradicating group A streptococci from the pharynx. For example cefpodoxime proxetil given twice daily for 10 days is comparable to penicillin V given three times daily for 10 days in achieving a clinical cure and appears to be significantly superior to penicillin in eradicating group A streptococci from the pharynx. Preliminary studies from Europe and the United States strongly suggest that 5-day therapy with cefpodoxime (or other selected oral cephalosporins) is at least as effective, clinically and microbiologically, as 10-day therapy with penicillin V. Further clinical trials are warranted to confirm the adequacy of 5 day treatment and to assess the efficacy of cefpodoxime and other agents in preventing rheumatic fever. PMID- 7792130 TI - Temporal properties of colour and shape priming: evidence of multiple components of attention. AB - It has been shown in several studies that the selection of letters or numerals from an array can occur efficiently if criteria such as location, colour, shape, or size are used. It is also known that there are at least two components of spatial attention, the transient exogenous and the sustained endogenous. An interesting question is whether it is possible to elicit similar components when colour or shape information is used as a selection criterion. Experiments are reported the aim of which was to try to produce colour or shape precue effects on location and colour/shape discrimination accuracy, and to determine the minimum latency of these effects by sampling numerous cue lead times from 0 ms to 1000 ms. The results showed that, although accuracy did not increase monotonically with increased cue lead time, there were two transient peaks of performance at cue lead times of 0-200 ms, culminating at 30-50 ms and at 160-200 ms. It is suggested that the first component reflects nonspecific exogenous activation, triggered by the onset of a cue; the second component, in turn, may reflect feature-specific endogenous activation related to selection by colour or shape. PMID- 7792131 TI - The dependence of two-dimensional shape perception on orientation. AB - While it is true that in daily life we generally recognize objects regardless of their orientation, previous experiments involving novel shapes indicate a decline in recognition when these are tested in altered orientation. Here the question is raised of whether there is a component of shape perception based purely on the geometry of an object, independent of orientation. By means of two tests designed to eliminate awareness of change of orientation, one more stringent than used heretofore, it was found that shape perception is dependent on orientation. The apparent contradiction between these findings and the apparent orientation-free character of recognition in daily life is discussed. PMID- 7792132 TI - Infants perceive spatial structure specified by line junctions. AB - Lines in drawings can be perceived as the corners where surfaces intersect, outer boundaries of surfaces, or as markings on a surface. In this study infants' ability to distinguish between lines that indicate corners and edges and lines that indicate markings was investigated. Infants aged 7.5 months were habituated to line displays in which the lines specified a three-dimensional cube or two overlapping rectangles. Both displays contained lines indicating corners, edges, and surface markings. After habituation, infants viewed two test displays, one in which the corners or edges were deleted and one in which the surface markings were deleted. Infants looked significantly longer at the displays that lacked the corners or edges. The results suggest that infants attend to lines that depict corners and edges to a greater degree than they attend to lines that depict markings. Infants may do so because corners and edges specify the shapes of objects whereas markings do not. PMID- 7792133 TI - Stereokinetic effects with sharp and fuzzy illusory contours. AB - A black, 8-shaped pattern, whose centre of gravity is in the centre of a rotating disc, appears to split into two black discs rotating with phenomenal independent motion, orientation stability, and sliding of one on the other. The type of observed movement, the order of overlapping, and the extent of the stereokinetic depth in relation to the contour type and different dimensions of the pattern were investigated. The experimental data show that a fuzzy contour facilitates the stereokinetic effect. Furthermore, the extent of the stereokinetic depth has been found to be greater in case of fuzzy contour and vertical orientation of the pattern. These results are in contrast with the models in which this effect is considered as a problem of minimisation of distances or velocities. A vector model of the observed movement and an interpretation of the overlapping based on an energy approach are proposed. A tentative explanation of the stereokinetic depth for our patterns is put forward. PMID- 7792134 TI - Updating after rotational and translational body movements: coordinate structure of perspective space. AB - As people move through an environment, they typically change both their heading and their location relative to the surrounds. During such changes, people update their changing orientations with respect to surrounding objects. People can also update after only imagining such typical movements, but not as quickly or accurately as after actual movement. In the present study, blindfolded subjects pointed to objects after real and imagined walks. The role of rotational and translational components of movement were contrasted. The difficulty of imagined updating was found to be due to imagined rotation and not to imagined translation; updating after the latter was just as quick and accurate as updating after actual rotations and translations. Implications for understanding primary spatial orientation, the organization of spatial knowledge, and spatial imagination processes are discussed. PMID- 7792136 TI - Haptic discrimination of doubly curved surfaces. AB - Active haptic discrimination of mathematically well-defined surfaces was investigated. The quadric surfaces were defined in terms of 'shape index'--a quantity describing shape--and 'curvedness'--a quantity describing overall curvature. In these experiments shape index was varied and curvedness kept constant. The influence of laterality (unilateral versus bilateral discrimination) was tested in separate sessions. No influence of shape on the discrimination of solid objects was found. From the results an estimate can be made of the just-noticeable difference in terms of shape-index units. There was a significant effect of laterality on discrimination: performance with unilateral (successive) examination (both with left and with right hand) was better than with bilateral (simultaneous) examination. PMID- 7792135 TI - The role of surface information in object recognition: studies of a visual form agnosic and normal subjects. AB - Three experiments were conducted to explore the role of colour and other surface properties in object recognition. The effects of manipulating the availability of surface-based information on object naming in a patient with visual form agnosia and in two age-matched control subjects were examined in experiment 1. The objects were presented under seven different viewing conditions ranging from a full view of the actual objects to line drawings of those same objects. The presence of colour and other surface properties aided the recognition of natural objects such as fruits and vegetables in both the patient and the control subjects. Experiment 2 was focused on four of the critical viewing conditions used in experiment 1 but with a large sample of normal subjects. As in experiment 1, it was found that surface properties, particularly colour, aided the naming of natural objects. The presence of colour did not facilitate the naming of manufactured objects. Experiment 3 was focused on possible ways by which colour could assist in the recognition of natural objects and it was found that object naming was facilitated only if the objects were presented in their usual colour. The results of the experiments show that colour does improve recognition for some types of objects and that the improvement occurs at a high level of visual analysis. PMID- 7792137 TI - Effects of hypobaric hypoxia on histochemical fibre-type composition and myosin heavy chain isoform component in the rat soleus muscle. AB - Histochemical fibre-type composition and myosin heavy chain isoform component in the soleus muscle were studied in normoxic rats at postnatal ages of 5, 10, 15, and 20 weeks and in rats exposed to hypobaric hypoxia (460 torr) for 5 weeks from postnatal ages of 5, 10, and 15 weeks. The increase in the percentage of type I fibres and the concomitant decrease in that of type IIa fibres in the soleus muscle of normoxic rats were observed until 15 weeks of age. On the other hand, no change in the fibre-type composition of the muscle during postnatal development was observed in hypoxic rats, irrespective of the age at which they were exposed to hypoxia. The changes in the myosin heavy chain isoform component (MHC I and MHC IIa) of the muscle during postnatal development and by hypoxia corresponded well with those in the muscle fibre-type composition. It is concluded that hypobaric hypoxia inhibits the growth-related shift of muscle fibre-types from type IIa to type I and of myosin heavy chain isoforms from MHC IIa to MHC I in the rat soleus muscle, and that there are no changes in the muscle fibre-type composition or the myosin heavy chain isoform component caused by hypoxia after the shifts in these parameters which occur during postnatal development are completed. PMID- 7792138 TI - Biophysical, pharmacological and developmental properties of ATP-sensitive K+ channels in cultured myotomal muscle cells from Xenopus embryos. AB - Unlike mammalian muscle cells in culture, cultured myotomal muscle cells of Xenopus embryos express ATP-sensitive K+ (KATP) channels. The KATP channels are blocked by internal ATP (half-maximal inhibition K0.5 = 16 microM) and to a lesser extent by internal ADP, are voltage independent, have an inward rectification at positive potentials and are inhibited by glibenclamide (K0.5 = 2 microM). Surprisingly, these KATP channels are not sensitive to K+ channel openers such as cromakalim. Opening of these KATP channels does not occur under normal physiological conditions. It is elicited by metabolic exhaustion of the muscle cell and it precedes the development of an irreversible rigor state. Neither intracellular acidosis nor an increase of intracellular Ca2+ are involved in KATP channel opening. Different types of K+ channels are successively expressed after plating of myotomal muscle cells: (1) sustained delayed-rectifier K+ channels; (2) KATP channels; (3) inward-rectifier K+ channels; (4) transient delayed-rectifier K+ channels. The current density associated with KATP channels far exceeds that of voltage-dependent K+ channels. Innervation controls the expression of these KATP channels. Co-culture of muscle cells with neurons from the neural tube decreases the number of active KATP channels per patch. Similarly, in situ innervated submaxillaris muscle of tadpoles at stage 50-55 has a very low density of KATP channels. PMID- 7792140 TI - Adenosine triphosphate-dependent K currents activated by metabolic inhibition in rat ventricular myocytes differ from those elicited by the channel opener rilmakalim. AB - Adenosine triphosphate (ATP) dependent potassium channels (KATP channels) in heart ventricular muscle cells can be activated by depletion of intracellular ATP stores as well as by channel openers. In the present study we examined whether properties of KATP channels are dependent on the mode of activation. Whole-cell and single-channel currents were investigated by use of the patch-clamp technique in isolated ventricular rat myocytes. The channel opener rilmakalim dose dependently activated whole-cell currents [concentration for half-maximal activation (EC50) = 1.1 microM, Hill coefficient = 3.1, saturation concentration 10 microM]. Metabolic inhibition with 2-deoxy-D-glucose (10 mmol/l) also activated KATP currents after a time lag of several minutes. These currents were about two-fold higher than the rilmakalim-activated currents (rilmakalim activated current 3.9 +/- 0.2 nA, 2-deoxy-D-glucose-activated current 8.1 +/- 0.9 nA; both recorded at 0 mV clamp potential). While the rilmakalim-activated current could be blocked completely and with high affinity by the sulphonylurea glibenclamide [concentration for half-maximal inhibition (IC50) = 8 nM, Hill coefficient = 0.7] the 2-deoxy-D-glucose-activated current could only be blocked partially (by maximally 46%) and higher glibenclamide concentrations were needed (IC50 = 480 nM, Hill coefficient = 0.8). The partial loss of blocking efficiency after metabolic inhibition was not restricted to glibenclamide but was also observed with the sulfonylureas glimepiride and HB 985, as well as with the non sulfonylureas HOE 511 and 5-hydroxy-decanoate. Single-channel studies were in accordance with these whole-cell experiments. Both rilmakalim and metabolic inhibition with the uncoupler carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) activated single channels in the attached mode, where the number of current levels was significantly higher in the case of FCCP. Rilmakalim activated channels were completely blocked by 10 microM glibenclamide, whereas several single-channel levels appeared in the presence of 100 microM glibenclamide after metabolic inhibition. In conclusion, after metabolic inhibition the amplitude of the activated KATP current is about twice as high as under saturating concentrations of the opener rilmakalim. Moreover, channels activated by metabolic inhibition lost part of their sensitivity to known channel blockers. PMID- 7792139 TI - Control of pulmonary vascular smooth muscle tone by sarcoplasmic reticulum Ca2+ pump blockers: thapsigargin and cyclopiazonic acid. AB - The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (beta escin)-skinned arterial strips, application of TG (0.1-1 microM) or CPA (0.5-10 microM) prior and throughout the loading procedure of the internal Ca2+ stores (0.3 microM free Ca2+ ions for 8-10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 microM) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca(2+)-containing solution (2.5 mM for 10 min), followed by incubation in a Ca(2+)-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca2+. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca2+ ions was not antagonized by verapamil (10 microM) or nifedipine (1 microM) but was blocked by La3+ (50 microM) and Co2+ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca2+] [0.1-10 mM, concentration for half maximal effect (EC50) = 0.85 mM], not modified by the reduction of the external [Na+] (from 130 to 10 mM) and decreased by depolarization of the strip using K(+)-rich (30-120 mM) solutions. Under the latter condition, 38 +/- 9 and 83 +/- 4% reduction (n = 5) was observed in the presence of 60 and 120 mM K+ respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792142 TI - Calcium is not involved in the cAMP-mediated stimulation of Cl- conductance in the apical membrane of Necturus gallbladder epithelium. AB - The permeability properties of the forskolin-stimulated Cl- conductance in the apical membrane of Necturus gallbladder epithelium and the possible participation of intracellular Ca2+ in its stimulation have been investigated. The anion selectivity sequence as derived from biionic potential measurements (SCN- > I- approximately NO3- > Br- > Cl- >> ISE-) differed from the sequence derived from measurements of apical membrane resistance (NO3- approximately Br- approximately Cl- > SCN- > I- approximately ISE-). Accordingly, the conductance was inhibited by SCN- and I- which, from the potential measurements, appeared to be more permeable than Cl-. This finding agrees with observations of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel reported recently. However, none of the commonly used Cl- channel blockers, such as 5-nitro-2-(3 phenylpropylamino)-benzoic acid (NPPB), 4,4'-diisothiocyanatostilbene-2,2' disulphonic acid (DIDS), anthracene-9-carboxylic acid (9-AC) and glibenclamide reduced this conductance in Necturus gallbladder. In contrast to the situation in most other epithelia, elevation of intracellular Ca2+ concentration ([Ca2+]i) by ionomycin stimulated only K+ conductance and not that of Cl- in the apical cell membrane. Chelation of intracellular Ca2+ did not prevent the stimulation of Cl- conductance by forskolin. This indicates that [Ca2+]i does not have even a permissive role in the cyclic adenosine monophosphate-(cAMP)-mediated stimulation process, as would have been expected if exocytosis was involved. Further evidence against the involvement of exocytosis in the stimulation process came from the observation that the stimulation was not associated with an increase in apical membrane capacitance and was not suppressed by disruption of the cytoskeleton by preincubation of the tissue with cytochalasin D. The data indicate that Necturus gallbladder epithelium contains homologues of the CFTR Cl- channel which reside permanently in the apical cell membrane and which can be stimulated by a cAMP dependent phosphorylation process without involvement of cell Ca2+ or exocytosis. PMID- 7792141 TI - Arachidonic acid inhibits hormone-stimulated cAMP accumulation in the medullary thick ascending limb of the rat kidney by a mechanism sensitive to pertussis toxin. AB - The possible regulation of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by arachidonic acid (AA) was studied in segments, microdissected from the rat kidney, which are sensitive to arginine vasopressin (AVP). In the presence of 5 microM indomethacin, the addition of 5 microM AA did not impair AVP dependent cAMP accumulation (measured during 4 min at 35 degrees C) in the cortical or outer medullary collecting tubule, but decreased this response in the thick ascending limb with an inhibition much more pronounced in the medullary portion (MTAL) than in the cortical portion. In MTAL, the response to 10 nM AVP was inhibited by 34.4 +/- 9.6% (SEM) and 65.8 +/- 5.4% with 1 microM and 5 microM AA, respectively, N = 5 experiments. AVP-, glucagon- and calcitonin-sensitive cAMP levels in MTAL were inhibited by 5 microM AA to a similar extent. AA-induced inhibition was unaffected by the presence of inhibitors of AA metabolism: (1) either 10 microM indomethacin or 50 microM ibuprofen added to all media; (2) a 10 min pre-incubation and a 4-min incubation of MTAL samples with 10 microM eicosa 5,8,11,14-tetrayonic acid, (3) a 1-h preincubation with either 30 microM SKF 525A, 20 microM ketoconazole, or 20 microM nordihydroguariaretic acid. In contrast to AA, 11 other saturated or unsaturated fatty acids had no inhibitory effect on the AVP-dependent cAMP level. In fura-2-loaded MTAL samples, AA induced a slow increase of the intracellular calcium concentration ([Ca2+]i) which reached 21.0 +/- 3.8 nM and 92.9 +/- 21.4 nM over basal values (n = 11) at 2 min and 4 min, respectively, after the beginning of the superfusion of 5 microM AA. AA-induced inhibition of AVP-dependent cAMP accumulation was due neither to the increase in [Ca2+]i elicited by AA, nor to an activation of protein kinase C because this inhibition: (1) was not blocked when MTAL samples were incubated either in zero Ca2+ medium, or in the presence of 1,2-bis(2-aminophenoxy)ethane N, N, N', N'-tetraacetic acid (BAPTA) to chelate [Ca2+]i, and (2) it was not reproduced by a pre-treatment of MTAL segments with a phorbol ester. Pre incubation of MTAL (6 h at 35 degrees C) with 500 ng/ml pertussis toxin (PTX) prevented AA-induced inhibition: in the presence of PTX inhibition was 24.7 +/- 6.6% vs 10 nM AVP, as compared to 81.6 +/- 4.0% in control groups, i.e in the absence of PTX, N = 6.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7792143 TI - Cell membrane stretch in osteoclasts triggers a self-reinforcing Ca2+ entry pathway. AB - Many cell types respond to mechanical membrane perturbation with intracellular Ca2+ responses. Stretch-activated (SA) ion channels may be involved in such responses. We studied the occurrence as well as the underlying mechanisms of cell membrane stretch-evoked responses in fetal chicken osteoclasts using separate and simultaneous patch-clamp and Ca2+ imaging measurements. In the present paper, evidence is presented showing that such responses involve a self-reinforcing mechanism including SA channel activity, Ca(2+)-activated K+ (KCa) channel activity, membrane potential changes and local and general intracellular Ca2+ ([Ca2+]i) increases. The model we propose is that during membrane stretch, both SA channels and KCa channels open at membrane potential values near the resting membrane potential. SA channel characterization showed that these SA channels are permeable to Ca2+. During membrane stretch, Ca2+ influx through SA channels and hyperpolarization due to KCa channel activity serve as positive feedback, leading ultimately to a Ca2+ wave and cell membrane hyperpolarization. This self reinforcing mechanism is turned off upon SA channel closure after cessation of membrane stretch. We suggest that this Ca2+ entry mechanism plays a role in regulation of osteoclast activity. PMID- 7792144 TI - A confocal scanning laser microscope for quantitative ratiometric 3D measurements of [Ca2+] and Ca2+ diffusions in living cells stained with Fura-2. AB - A confocal scanning laser microscope (CSLM) for observation and quantitative ratiometric measurements of the intracellular dynamics of Ca2+ ions in living neurons has been developed. The instrument consists of a UV-enhanced CSLM, an optical arrangement providing simultaneous excitation at two wavelengths, an electronic arrangement for processing the simultaneous fluorescence response, and software for computing the absolute Ca2+ concentrations, ([Ca2+]). The instrument can be used for any excitation ratiometric measurements, provided that the dye substance used is excitable by wavelengths between 334 nm and 750 nm (such as, e.g. Fura-2). The spatial resolution of the CSLM, as well as a temporal resolution of 20 ms per line (maximum sampling rate) for dynamic measurements are provided by the instrument. Using Fura-2 in calibrated Ca2+ buffer solutions, the instrument measures [Ca2+] between 0 and 1.35 mumol.l-1 with an error of less than 1%. The capability of the instrument to measure absolute [Ca2+] was verified by recording fluorescence images of test solutions with well defined [Ca2+] values (Molecular Probes, Eugene, Ore., USA, C-3009 calibration solutions). In order to verify the dynamic capability of the instrument in real biological specimens, fluorescence changes of Fura-2 that were due to an intracellular flux of Ca2+ ions, and to an increase of [Ca2+]i (the intracellular Ca2+ concentration) have been recorded in Fura-2-loaded cultured cells of the line TE 671. PMID- 7792145 TI - Enhancement of an L-type calcium current in AtT-20 cells; a novel effect of the m4 muscarinic receptor. AB - Activation of muscarinic receptors has been shown to inhibit L-type calcium conductances by mechanisms sensitive to pertussis toxin (PTX). In this study we show that agonist stimulation of the m4 muscarinic receptor leads to an increase in an L-type calcium conductance in the AtT-20 pituitary cell line, by a PTX sensitive mechanism. The amplitude of the dihydropyridine (DHP)-sensitive or L type calcium current was increased by acetylcholine (ACh), with no shift in the voltage dependence. This action of ACh was completely inhibited by PTX pre treatment. Forskolin, cAMP and phorbol 12,13-dibutyrate reduced, while RpcAMPs, an inhibitor of cAMP-dependent protein kinase (PKA), increased the L-type calcium conductance. We propose that the m4 muscarinic receptor activates the L-type calcium channel by inhibition of adenylyl cyclase resulting in reduced cAMP levels and, hence, reduced PKA activity. This novel increase in calcium current via the m4 muscarinic receptor appears to reflect the coupling with an L-type channel of the D class, due to the sensitivity of the L-type calcium conductance to both DHPs and omega-conotoxin, and, thus, is distinct from the skeletal muscle and cardiac L-type channels of the C class previously studied. PMID- 7792146 TI - The variable coupling between force and myosin light chain phosphorylation in Triton-skinned chicken gizzard fibre bundles: role of myosin light chain phosphatase. AB - The mechanism responsible for the regulation of smooth muscle tone at low levels of myosin light chain (MLC) phosphorylation is still poorly understood. According to one model, so-called latchbridges, which contribute to force maintenance at low levels of MLC phosphorylation, are generated by dephosphorylation of attached and phosphorylated crossbridges. The model predicts that the force generated for a given level of MLC phosphorylation depends on the activity of the MLC phosphatase. We tested this hypothesis by reducing the activity of the phosphatase by at least 80% in two ways: inhibition with okadaic acid and extraction. Under both conditions, higher levels of MLC phosphorylation were required to support a given level of force, suggesting a decreased flux of attached phosphorylated to attached dephosphorylated crossbridges, as predicted by this model. Although, under both conditions, the relationship between force and MLC phosphorylation was shifted to the right, the curves did not superimpose as would have been expected if the phosphatase activity were the only determinant of the coupling between force and phosphorylation. In the extracted fibres, two more proteins, calponin and SM22, were significantly reduced in addition. Therefore, these proteins might be involved in modulating the relationship between force and MLC phosphorylation. PMID- 7792147 TI - The effects of calcium and calcium channel blockers on sodium pump. AB - The effects of 10 mM Ca2+ and Ca2+ channel blockers verapamil, diltiazem and flunarizine on the ouabain-sensitive electrogenic Na+, K+ pump activity of mouse diaphragm muscle fibres enriched with Na+ were compared with the changes in cytosolic [Ca2+]. The electrogenic Na+ pump activity produced by adding K+ to muscles previously bathed for 4 h in a K(+)-free, 2-mM [Ca2+] solution increased the resting membrane potential by about 18 mV. This hyperpolarization was completely inhibited after 10 min incubation in 10 mM Ca2+. Verapamil 10(-5) M, 10(-5) M diltiazem and 10(-7) M flunarizine effectively prevented the effect of elevated [Ca2+]. At these concentrations, these drugs did not affect the K(+) induced hyperpolarization. In mouse diaphragm, the basal cytosolic [Ca2+] measured by the fluorescent indicator 1-[2-(5-carboxyoxazol-2-yl)-6- aminobenzofuran-5-oxy]2-(2'-amino-5'-methylphenoxy)ethane-N,N,N',N '- tetraacetic acid acetoxymethyl ester (fura-2/AM) was 261 +/- 6 nM. After 4 h in a Liley K(+) free, 2 mM [Ca2+] solution, the cytosolic [Ca2+] increased to 314 +/- 28 nM. Increase in [Ca2+] from 2 to 10 mM caused a twofold increase of cytosolic [Ca2+] to 637 +/- 26 nM. This rise was, like the Ca(2+)-induced inhibition of electrogenic pump, prevented by 10(-5) M verapamil, 10(-5) M diltiazem and 10(-7) M flunarizine. The results suggest that substances which block Ca2+ entry into the cell prevent the Ca(2+)-induced inhibition of the Na+ pump. PMID- 7792148 TI - Cellular acidification occurs during anoxia in cultured, but not in freshly isolated, rabbit proximal tubular cells. AB - In a variety of cells it has been shown that acidosis is protective against anoxic injury. We have demonstrated previously that proximal tubule (PT) cells in primary culture were more resistant to anoxia-induced cell injury than were freshly isolated cells. Therefore, we asked the question of whether a difference in cellular acidification during anoxia could explain this difference in susceptibility to anoxia. To answer this question, intracellular pH (pHi) was measured during anoxic incubation of PT cells in culture and those that were freshly isolated. PT cells were incubated in an anoxic chamber at 37 degrees C after loading with 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM) or fura-2 acetoxymethyl ester (fura-2-AM). pHi and cytosolic free Ca2+ ([Ca2+]i) were measured by digital imaging fluorescence microscopy. During anoxia, pHi in cultured PT cells decreased from 7.3 +/- 0.1 to 6.8 +/- 0.1, whereas pHi in freshly isolated cells did not decrease significantly. In addition, the intrinsic buffering capacities (beta i) in cultured and freshly isolated PT cells were determined and turned out to be the same at a pHi greater than or equal to 7.3. Below pHi 7.3, beta i increased several fold in freshly isolated PT cells, and rose to significantly higher levels than in cultured PT cells. During 1 h of anoxia, cell viability of freshly isolated PT cells decreased significantly to 54% +/- 2% (P < 0.05), while no loss in viability was observed in cultured PT cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792149 TI - Characterization of the high-conductance Ca(2+)-activated K+ channel in adult human skeletal muscle. AB - Ca(2+)-activated K+ channels of a large conductance (BKCa) in human skeletal muscle were studied by patch clamping membrane blebs and by using the three microelectrode voltage-clamp recording technique on resealed fibre segments. Single-channel recordings in bleb-attached and inside-out modes revealed BKCa conductances of 230 pS for symmetrical and 130 pS for physiological K+ distributions. Open probability increased with membrane depolarization and increasing internal [Ca2+]. The Hill coefficient was 2.0, indicating that at least two Ca2+ ions are required for full activation. Kinetic analysis revealed at least two open and three closed states. An additional long-lived inactivated state, lasting about 0.5-20 s, was observed following large depolarizations, when extracellular K+ was lowered to physiological values. BKCa were blocked by three means: (1) externally by tetraethylammonium which reduced single-channel amplitude (IC50 approx. 0.3 mM); (2) internally by polymyxin B which decreased the open probability (IC50 approx. 5 micrograms/ml); and (3) externally by charybdotoxin which caused long-lasting periods of inactivation (IC50 < 10 nM). Measurements on resealed fibre segments at physiological [K+] were in accordance with the single-channel data: only when intracellular [Ca2+] was elevated did charybdotoxin (50 nM) reduce the macroscopic membrane K+ conductance with depolarizing voltage steps. PMID- 7792150 TI - Tetraethylammonium-insensitive, Ca(2+)-activated whole-cell K+ currents in rat submandibular acinar cells. AB - Using whole-cell patch-clamp techniques, we demonstrate, for the first time, that rat submandibular acinar cells contain a tetraethylammonium (TEA)-insensitive, Ca(2+)-activated K+ conductance which is not attributable to large conductance, voltage-sensitive, Ca(2+)-dependent K+ channels (maxi-K+ channels). Taken together with our recent K+ efflux and fluid secretion studies in intact rat submandibular gland, we postulate that the K+ conductance reported here may be involved in the basolateral K+ efflux pathway activated by cytosolic Ca2+ concentration during secretion by this gland. PMID- 7792151 TI - The emotional environment of older adults: a holistic nursing perspective. PMID- 7792152 TI - Encountering environment through interiority. PMID- 7792153 TI - A collage of awareness for a sustainable future. PMID- 7792154 TI - Family life after Hurricane Andrew: personal and phenomenological reflections. PMID- 7792156 TI - Environments experienced by hospital nurses during Hurricane Andrew. PMID- 7792155 TI - Emotional and environmental connections: impact of the Armenian earthquake. PMID- 7792157 TI - Voluntary simplicity: nurses creating a healing environment. PMID- 7792159 TI - Environmentally responsible clinical practice. PMID- 7792158 TI - In the gloom of the environmental crisis, can nurses afford to dwell in hope and be defined by the past? PMID- 7792160 TI - Environmental messages: experiencing the wisdom of the natural world. PMID- 7792161 TI - Environmental connections and reawakened spirit. PMID- 7792163 TI - An ecofeminist look at animal research. PMID- 7792162 TI - The environment: alive, whole, and interacting. PMID- 7792164 TI - The environment as a curricular concept in professional nursing programs: a case study. PMID- 7792165 TI - Practicing environmental accountability: a mosaic of meanings for nursing. PMID- 7792166 TI - Endings and new beginnings. PMID- 7792167 TI - Nightingale, nursing, and the ecofeminists. PMID- 7792168 TI - Nurses as fairies in gumboots. PMID- 7792169 TI - Exploring ethical ways of being with another and earth, including life-style changes to promote a culture of simplicity. PMID- 7792170 TI - The Bright Alps Project: creating caring environments for people with disabilities. PMID- 7792171 TI - Toward a more friendly social environment for the patient: the role of the resident hospital relative. PMID- 7792174 TI - Divided we fall. PMID- 7792173 TI - Managing success. PMID- 7792172 TI - Professional development. Managing diabetes: revision notes (continuing education credit). PMID- 7792175 TI - Indecent exposure. PMID- 7792176 TI - The case for and against the practice of euthanasia. PMID- 7792177 TI - Euthanasia. Definitions and debate. AB - This paper looks at the origins and history of euthanasia and describes active and passive intervention. The author also describes the development of the various organisations advocating euthanasia or supporting those who wish to use it. Public opinion on the subject is explored, as well as the rights of patients and practitioners. PMID- 7792178 TI - Euthanasia and the legal situation in The Netherlands. AB - In The Netherlands a doctor may, under certain circumstances, avoid prosecution if he or she helps a patient to die who has persistently requested euthanasia. This paper describes the current legal situation. PMID- 7792179 TI - Euthanasia. The issue of resuscitation. AB - Euthanasia in this country is illegal, but issues surrounding 'do not resuscitate' guidelines raise the questions on the right to a death with dignity for many nurses. In this paper the author discusses the statement by the British Medical Association and the Royal College of Nursing on cardiopulmonary resuscitation and advises health practitioners to use this statement as a guideline for their own policy and framework in hospitals and not to accept this framework as implicit. PMID- 7792180 TI - Sociology in nurse education: help or hindrance? AB - Recent years have seen a dramatic increase in the role of the social and behavioural sciences in nurse education. In part this follows the UKCC's recommendations for Project 2000 curricula, but it can also be seen as a wider reaction to the domination of nursing knowledge by the so-called 'biomedical' model. Indeed, not only do pre-registration courses in nursing and midwifery now incorporate significant elements of sociology and psychology, but so, especially, do post-registration diploma and degree courses. Although this development is often regarded by nurse educators (many of whom either possess, or are in the process of acquiring degrees or post-graduate qualifications in the social sciences) as a positive step towards greater professionalism and autonomy within the nursing profession, there are a number of reasons why such assumptions should be regarded with caution. This paper explores some of the most important of these, and argues that the keenness with which nurse educators have embraced the discipline of sociology into the nursing curriculum, could in fact be seriously misplaced. PMID- 7792181 TI - Social Marxism, class conflict and health care. AB - In the first of a six-part series the sociological theories of Karl Marx are examined and related to the purported neutrality of medicine. The role of nursing within a Marxist analysis of the world is considered, and the value of such analysis is described. PMID- 7792183 TI - Complementary medicine. Nature cures. PMID- 7792182 TI - Scandinavian style of care. PMID- 7792184 TI - Older people: individual practices. PMID- 7792185 TI - HIV/AIDS. The family way. PMID- 7792186 TI - Unhealthy attitudes. PMID- 7792187 TI - Infection control. Knowledge of disinfection. PMID- 7792188 TI - Infection control. Motivation: the key factor. PMID- 7792189 TI - Seeing the light. PMID- 7792190 TI - Taken to task. PMID- 7792191 TI - Island reforms. PMID- 7792192 TI - Challenging ageism through our speech. AB - Aspects of ageism that are directed towards older people can sometimes be reflected in speech. This study puts some of the relevant literature to the test by finding out the opinions of some older people about the way they are spoken to and communicated with. The research suggests that ageism through speech is very real, but the reinforcements of these attitudes are perhaps also to do with the behaviour of older people themselves. PMID- 7792194 TI - A new approach to practice development in mental health. AB - This paper describes the structure and implementation of a training strategy in a mental health service. An approach was adopted which sought to combine the needs of staff, quality patient care and national agendas. PMID- 7792193 TI - Power of language in a ward for the care of older people. AB - This study examines nurse-patient interaction in a ward caring for older patients. The role of language in exerting control over patients is explored and the research confirms previous work which revealed that most of the observed interactions were brief, superficial and related to tasks. An inherent tension in the quality of communication expected from nurses and that which actually occurs is identified. It is recommended that attention to language, as a specific component of communication, is vital if nurses are to develop the skills necessary to interact with patients in a manner consistent with the demands of contemporary thinking in nursing. PMID- 7792195 TI - Managing occupational health services in NHS trusts. AB - This paper, the last in a series of six, reviews the areas to consider when managing occupational health provision in NHS settings. It covers the operational policy, which explains the functions of the occupational health service. It then discusses the staffing and structure of the service and how it fits into the rest of the organisation. The concluding section is perhaps the most important of all; without financial awareness, understanding and maintaining a budget, the manager of the occupational health service will not be successful. Previous papers in the series appeared on December 14, January 11, February 8, March 1 and April 12. PMID- 7792196 TI - The effects of psoriasis and its treatment: Part 1. AB - The first of a series of two papers on the subject describes a range of treatments for psoriasis. The pharmaceutical treatment of the condition is described together with consideration of the general support of the person affected. Treatment may be topical or systemic depending on the severity of the condition. PMID- 7792197 TI - Prejudice in practice. PMID- 7792198 TI - A disaffected profession. PMID- 7792199 TI - Fear busters. PMID- 7792200 TI - Midwives' journal. Implementing good practice. PMID- 7792201 TI - Midwives' journal. Feeding after mammoplasty. PMID- 7792202 TI - The pathologist's approach to the diagnosis of metabolic disease. AB - Many inborn errors of metabolism have tissue changes that suggest or indicate a diagnosis on morphologic bases. This emphasizes the involvement of the pathologist in the study of tissues obtained by biopsy as part of the diagnostic workup of cases with clinical evidence suggesting a metabolic disorder. Some of these diseases involve proteins with enzymatic activity with a consequent backlog of precursor metabolites. If these metabolites are insoluble or compartmentalized in cells, they accumulate in tissues. The diagnosis in those cases rests on establishing the nature of the accumulated materials and their topographic distribution. In some storage diseases, the abnormal substance can be identified in the affected tissues by histochemistry or ultrastructure. Another group of inborn disorders of metabolism produce changes in subcellular organelles such as peroxisomes and mitochondria. A third group is expressed by rather unique tissue changes which strongly suggest the diagnosis of metabolic disease. PMID- 7792204 TI - Prognostic significance of T-cell infiltrates, expression of beta 2-microglobulin and HLA-DR antigens in breast carcinoma. AB - In this study immunohistological staining was used to assess the presence of T cell infiltrates and the expression of beta 2-microglobulin (beta 2-m) and HLA-DR antigens on tumor cells of 75 ductal invasive carcinomas. The results were compared with the morphometric prognostic index (MPI) that seems to be the most accurate prognostic predictor. The extent of T-cell infiltrates differed widely between tumors, but statistically significant correlation was found only with the lymph node status, namely, tumors with a high degree of infiltration had predominantly negative lymph nodes and vice versa (p < 0.05). Only 19 (25.3%) out of 75 carcinomas were beta 2-m+, 34 cases (45.3%) showed heterogeneous staining pattern and 22 tumors (29.3%) were completely negative. We could not find any significant correlation between beta 2-m expression and MPI or T-cell content. While normal breast epithelium was always HLA-DR negative, tumor cells displayed positivity in 25 cases (33.3%), 5 tumors (6.7%) were completely positive and 20 tumors (26.7%) displayed only focal expression of class II antigens. This expression did not correlate with any single prognostic parameter, nor with MPI. The results suggest that T-cell infiltrates and the expression of histocompatibility antigens can not be accepted as prognostic indicators in breast carcinoma. PMID- 7792203 TI - The localization of lipopolysaccharide in an endotoxemic rat liver and its relation to sinusoidal thrombogenesis: light and electron microscopic studies. AB - The distribution of lipopolysaccharide (LPS) and sequential thrombus formation in the liver was investigated by immunohistochemical and cytochemical techniques in endotoxemic rats, using horseshoe crab factor C, a specific ligand for biologically active LPS, a monoclonal antibody against it, and rabbit anti-rat fibrinogen IgG. One hour after the intravenous administration of LPS (5 mg/kg), LPS was localized in the secondary lysosomes of Kupffer cells and in the vesicles of endothelial cells, mainly at the peripheries of the hepatic lobules. Small necrotic foci of hepatic tissue were scattered close to the LPS-containing Kupffer cells, and were frequently associated with infiltration of neutrophils and deposition of fibrin. Three hours after the administration of LPS, the immunohistochemical reaction of LPS became stronger and was mostly confined to Kupffer cells. Strands of polymerized fibrin were frequently observed on both the surface of the LPS-containing Kupffer cells and on endothelial cells. These findings suggest that the activation of the coagulation cascade in plasma is first initiated, even though only transiently, by hepatic necrosis which is probably caused by LPS-activated leukocytes, and then by the procoagulant activity expressed on the surface of both Kupffer cells and endothelial cells. Fibrinogen-related antigens were also immuno-ultrastructurally detected in the lysosomes of Kupffer cells three hours after the injection of LPS, which suggested that the Kupffer cells phagocytozed and degraded fibrin. Therefore Kupffer cells in endotoxemia may closely participate in both the sinusoidal thrombogenesis and degradation of fibrin. PMID- 7792205 TI - Stereologic parameters of nuclear ultrastructure as markers of the steroid receptor status in breast cancer epithelium. AB - The nuclear specific surface density (Sv/Vv), mean nuclear area (A) and numerical density (Nv) of tumor cell nuclei from 30 primary invasive female breast carcinomas with known concentrations of estrogen and progesterone receptors (ER and PR), were morphometrically analyzed at the ultrastructural level. It was found that carcinomas with concordant positive ER and PR status contained significantly higher number of smaller nuclei per volume unit of epithelium (mean Nv = 1.5 x 10(6) mm-3, mean A = 27 microns 2), than carcinomas of negative concordant receptor status (mean Nv = 0.8 x 10(6) mm-3, mean = 37 microns 2). Tumor cell nuclei of the former frequently displayed an elliptic shape (mean Sv/Vv = 1.16 microns-1), and had deeply invaginated surfaces, whereas nuclei of the latter were more frequently ball-shaped and exhibited a smooth-surface (mean Sv/Vv = 0.88 microns-1). The numerical density Nv (NUC/EPI) of tumor cell nuclei turned out to be a most reliable morphological marker of the concordant ER and PR status (overall efficiency = 84%, p < 0.01). The nuclear surface and volume ratio and mean nuclear area also appear to be reliable markers for terminal stages of the biochemical differentiation of breast carcinoma (overall efficiency = 79%, p < 0.05). PMID- 7792207 TI - Carcinoid tumour complicating inflammatory bowel disease. A study of two cases with review of the literature. AB - Two cases of carcinoid tumour complicating inflammatory bowel disease (IBD) are presented. Both tumours were located in the appendiceal tip. The first case occurred in a man with Crohn's disease (CD), and the second one in a woman suffering from ulcerative colitis (UC). Histochemical and immunohistochemical studies were not allowed on case 1 because the tumour was not still present on serial sections of the appendix. On case 2, tumour cells were not reactive with Grimelius and Masson-Fontana stainings, but were strongly stained with anti keratin and anti-chromogranin monoclonal antibodies (MAb), and faintly expressed neuron specific enolase (NSE), and Leu-7. Both cases occurred in inflammatory or damaged mucosa which exhibited Paneth cell metaplasia and hyperplasia and areas indefinite for dysplasia. Along with these lesions, hyperplasia of enteroendocrine cells was pointed out in the neighbouring appendiceal and colonic mucosa by means of anti-chromogranin MAb. These data suggest that the association of carcinoid tumour with IBD, albeit rare, is not coincidental and is the result of hyperplastic and dysplastic troubles that may involve enteroendocrine cells as well as such other derivatives of digestive stem cells as columnar cells, goblet cells and Paneth cells. PMID- 7792206 TI - Creatine kinase isoenzymes as markers of differentiation in rhabdomyosarcoma cells in culture. AB - Rhabdomyosarcomas have been classified on the basis of their degree of differentiation, a feature closely related with their response to chemotherapy. We recently reported the role of creatine kinase isoenzymes as tumoral markers in the diagnosis of rhabdomyosarcoma. The present study was designed to determine whether these isoenzymes are also good markers of the degree of differentiation of these neoplasm. Dimethyl sulfoxide, a well-known differentiating agent, was used to induce myogenic differentiation. This agent increased CK-MM and/or CK-MB fractions, and decreased CK-BB isoenzyme in rhabdomyosarcoma cell lines. The variable behavior of MCK-1 macromolecule was unrelated to the degree of differentiation. Our findings suggest that CK-MM, CK-MB and CK-BB isoenzymes are good markers of the degree of differentiation in rhabdomyosarcomas and could be used as specific markers of prognostic and diagnostic value. PMID- 7792208 TI - Sarcoidosis of the thyroid gland manifested initially as thyroid tumor. AB - A rare case of a patients with sarcoidosis of the thyroid gland, who was preoperatively diagnosed as having thyroid carcinoma and who had no other clinical features of sarcoidosis, is reported. Thyroidectomy specimen revealed numerous noncaseating, epithelioid granulomas in the thyroid tissue. Mycobacteria, fungi and foreign body material were not identified. Similar granulomas were also found in the lymph nodes and muscular tissue adjacent to the thyroid gland and parathyroid gland After the diagnosis of sarcoidosis of the thyroid, systemic examination failed to reveal any involvement in other sites, including lung, eye and skin. This case demonstrated that sarcoidosis can manifest initially as a thyroid tumor with no other evidence of disease. PMID- 7792209 TI - Renal and hepatic angiomyolipomas in a child without evidence of tuberous sclerosis. AB - A renal neoplasia, displaying the typical features of angiomyolipoma (an admixture of smooth muscle cells, mature adipocytes and tangles of thick-walled blood vessels) was found in a nine-year-old boy. In addition, cytoplasmic crystalloid structures and HMB 45 positivity were found in smooth muscle cells. Similar findings were also observed in a small nodule of the liver. According to literature data, angiomyolipoma is very rare in children and almost exclusively associated with tuberous sclerosis. Our case suggest that the diagnostic hypothesis of angiomyolipoma can not be disregarded when a renal mass is identified in a young patient even in a clinical setting other than tuberous sclerosis. PMID- 7792210 TI - What's new in managing health hazards in pathology departments. AB - Health hazards related to activities performed in pathology departments have represented, in recent years, an increasing concern among pathologists and pathology technicians. The major occupational health problems encountered in pathology departments are reviewed. They include biological hazards (tuberculosis, hepatitis, HIV, other infectious diseases), chemical hazards (formaldehyde, xylene(s), aromatic amines, methacrylates, glutaraldehyde, latex) and physical hazards (cut injuries, accidental fires, radiation). Current data suggest that infections (particularly, tuberculosis and hepatitis) still represent the more relevant risk. Exposure to HIV and Creutzfeldt-Jakob agent may be highly harmful but containment measures have been proven to be effective. The actual adverse effects due to chemicals seem to be less alarming than was previously believed. Attaining a safe work environment is an inherent element of good quality assurance management. This task is largely a matter of information, education, organization and common sense. Well-designed premises, efficient equipment and well-trained personnel are the keys to preventing and minimizing hazardous exposures. In order to provide current information that may be used by pathology staff to implement the functional quality of the workplace, organizational and preventive measures are described. PMID- 7792211 TI - Not all hemangiomas look like strawberries: uncommon presentations of the most common tumor of infancy. AB - The typical appearance of cutaneous hemangiomas of infancy is well known. We studied unusual manifestations of this common tumor. We reviewed over 500 hemangiomas in the registry of the Vascular Anomalies Program at Boston Children's Hospital. We found four uncommon morphologic variations: deep hemangiomas with normal overlying skin (n = 12); macular hemangiomas with a port wine stainlike appearance (n = 6); bossed hemangiomas with telangiectasia and peripheral pallor (n = 5); and hemangiomas with persistent fast flow (n = 3). Deep and superficial (macular) varieties regressed at a normal rate. Telangiectatic (bossed) hemangiomas, however, involuted rapidly, usually before 1 year of age. Hemangiomas with persistent fast flow required either resection or sclerotherapy for complications in early childhood. PMID- 7792212 TI - The frequency of erythromycin-resistant Staphylococcus aureus in impetiginized dermatoses. AB - A trend toward increasing resistance of Staphylococcus aureus to standard antibiotic therapy has been reported. Specimens were taken from 98 patients in our outpatient staff clinic who had clinical signs of superficial skin infections. Patients with erythromycin-resistant S. aureus were contacted by telephone or seen in clinic. The organism was found in 87% of patients. Twenty two (26%) of the 85 cultures that grew S. aureus were resistant to erythromycin. Treatment failure occurred in one of these patients. We conclude that S. aureus is the most common causative organism in secondary skin infections and impetigo in our patient population. Despite significant erythromycin resistance, there was a low frequency of treatment failure in this group. Erythromycin may still be a reasonable agent in the treatment of uncomplicated superficial skin infections in our community at this time. PMID- 7792213 TI - Childhood acquired epidermolysis bullosa. AB - We present the ninth case of epidermolysis bullosa acquisita (EBA) reported in children. As in most of the other childhood cases, the 7-year-old boy described herein had an acute, widespread, inflammatory vesiculobullous eruption with oral involvement. Indirect immunofluorescence on salt-split skin as well as Western immunoblot confirmed the diagnosis of EBA. The patient responded to combined prednisone and dapsone, and was maintained with dapsone alone. PMID- 7792214 TI - Erythrokeratoderma variabilis: case report and review of the literature. AB - A 5-month-old boy with erythrokeratoderma variabilis is presented. The parents noted that the asymptomatic erythematous plaques changed over the course of hours to days. Topical therapy with retinoic acid proved ineffective. A brief review of the literature is presented. PMID- 7792215 TI - Branchio-oculo-facial syndrome and dermal thymus: case report and review of the literature. AB - We report a patient affected by the rare branchio-oculo-facial syndrome. Histologic study of the branchial clefts showed thymic remnants. A scanning electron microscopic study of the hair was also performed. The clinical features of the patient were compared with those of other patients reported in the literature. PMID- 7792217 TI - Eosinophilic panniculitis. AB - Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder. PMID- 7792216 TI - A case of infantile febrile psoriasiform dermatitis. AB - An infant suffered from psoriasiform dermatitis complicated by severe constitutional symptoms. During his 12 months of hospitalization, the symptoms exacerbated periodically despite numerous therapeutic trials. Histologic findings revealed lichenoid psoriasiform dermatitis with striking eosinophilic necrosis of epidermal cells and satellite cell necrosis. Immunohistochemically, CD1+ Langerhans cells had almost disappeared, and CD8+ cytotoxic-suppressor T cells were predominant over CD4+ helper-inducer T cells in the epidermis. These findings in the skin biopsy specimens suggested some similarity to graft-versus host disease but no known cause of that disorder was proved. Finally, methotrexate was effective. The patient became afebrile, and his skin lesions improved, leaving almost no scarring. This patient seems to have had specific clinical features that do not correspond with any of the known dermatitis. Clinical, histologic, and laboratory findings did not uncover any etiologic factors. PMID- 7792218 TI - Pyoderma gangrenosum and sterile multifocal osteomyelitis preceding the appearance of Takayasu arteritis. AB - A 9-month-old infant had pyoderma gangrenosum (PG) and sterile osteomyelitis. Three years later the patient developed Takayasu arteritis (TA). Sterile osteomyelitis was reported in approximately 30 patients with different skin lesions, but never together with pyoderma gangrenosum. The association of PG and TA has been reported rarely, and then mainly in adults or in children over age 9 years. This rare association should alert physicians with a case of infantile PG of unknown etiology to consider the possible diagnosis of TA. PMID- 7792219 TI - Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E. AB - We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature. PMID- 7792220 TI - Apocrine chromhidrosis involving the areolae in a 15-year-old amateur figure skater. AB - Apocrine chromhidrosis is a rare disease frequently localized to the face or axillae, and rarely has been reported to occur around the breasts. We report a 15 year-old amateur figure skater who displayed localized chromhidrosis around her areolae. The most common precipitating event was exercise. She was treated topically with capsaicin cream 0.025% with a subsequent decrease in symptomatology. PMID- 7792221 TI - Fixed drug eruption on the tongue of a 4-year-old boy. AB - A 4-year-old boy had a rare fixed drug eruption due to amoxicillin and confined to the tongue. Avoidance of the drug resulted in complete clearance within three months. PMID- 7792222 TI - Treatment of childhood dermatophyte infections with oral terbinafine. AB - Over the past four years terbinafine has become established as an effective systemic antimycotic agent with an excellent safety profile. However, experience with its use in children is very limited. We report the effective treatment of five children with oral terbinafine. PMID- 7792223 TI - What syndrome is this? Ollier disease + vascular lesions: Maffucci syndrome. PMID- 7792224 TI - Multiple cutaneous nodules in a newborn. PMID- 7792225 TI - Atypical pityriasis rosea in a 2-year-old. PMID- 7792227 TI - UVB phototherapy in childhood psoriasis. PMID- 7792226 TI - Treatment of chronic bullous dermatosis of childhood with oral dicloxacillin. PMID- 7792228 TI - Golf tee hairs in Netherton disease. AB - We present a case of Netherton disease, where the hairs lacked the characteristic microscopic feature of trichorrhexis invaginata. In its place were certain hairs with a golf tee morphology. These represent the proximal half of the invaginate node seen in typical Netherton disease. Scanning electron microscopy demonstrated the three-dimensional quality of this abnormality, which is subtle when assessed by light microscopy alone. We describe this sign so that it might be recognized when seen in isolation, as here, and allow the diagnosis of Netherton disease to be confirmed. PMID- 7792229 TI - Selection for high eight-week body weight in normal and dwarf chickens under high protein and high-energy diets. AB - A study was conducted to examine genetic parameters associated with selection for high 8-wk BW in normal and dwarf Athens Canadian randombreds under two nutritional environments (high protein and high energy) and to determine the influence of the selection diet on subsequent water to feed ratios and abdominal fat levels. High-protein lines (HP) received a diet containing 25% CP and 3,100 kcal ME/kg, whereas high-energy lines (HE) received a 22% CP diet containing 3,200 kcal ME/kg. Body weights, selection gains, selection differentials, and heritabilities were similar for normal HP and HE lines. There was evidence, however, that the realized heritability was greater in the HE than the HP dwarf line. Similar selection differentials indicate that this difference was apparently due to the expression of greater genetic variation in the HE dwarf line. Water intake, feed intake, water to feed ratio, and abdominal fat data for the four lines under "selection" and "reciprocal" environments differed between experiments. In Experiment 1, when fed the HE diet, normal birds selected under the HP environment had higher (P < .05) water to feed ratios and lower abdominal fat levels than contemporaries selected under the HE diet. However, these differences were not significant in Experiment 2. PMID- 7792230 TI - The influence of genetic changes in body weight, egg production, and body conformation on organ growth of turkeys. AB - Measurements were made on the breast with bone (BWB), a demand organ, and various supply organs in mature turkeys (approximately 40 wk of age) from various lines of turkeys to determine the influence of selection for increased egg production, BW, and body conformation on resource allocation. Comparisons made were: 1) a line (E) selected long-term for increased egg production and its randombred control (RBC1); 2) a line (F) selected long-term for increased 16-wk BW and its control (RBC2); 3) the F line with a commercial sire line (C); and 4) the RBC1 line and a randombred control (RBC3) that was formed from the F and C lines. Data were analyzed on an absolute basis and after adjustment to a common BW by covariance analysis. The only major change in organ sizes that occurred that could not be accounted for by differences in BW was in the E line. The actual and relative weights of total supply organs decreased and the relative weight of the BWB increased in the E line when compared with its randombred control. Selection for increased BW in the F line did not result in a relative change in BWB. The BWB weight was relatively heavier in the C line than in the F line. The relative amount of BWB was slightly but significantly different in the two randombreds (RBC1 and RBC3) formed 29 yr apart. Weight of the gizzard did not increase at the same rate as BW in two large-bodied lines (F and RBC3). PMID- 7792231 TI - Influences of age at final beak trim on the productive performance of commercial layers. AB - Two commercial egg-type strains were beak-trimmed at 10, 10 and 63, or 10 and 84 d. There were no interactions between strain and beak trimming treatment. Pullet feed consumption was significantly reduced within the 14-d period following beak trimming at 63 or 84 d. Total pullet feed consumption (1 to 126 d) was significantly lower among birds trimmed twice than among those trimmed only at 10 d. At 126 d, body weight of pullets trimmed at 10 and 84 d or 10 and 63 d was significantly less than that of those trimmed only at 10 d. Pullet mortality was not significantly influenced by beak trimming treatments. No significant effects of beak trimming treatments on layer mortality, egg production, egg weight, egg mass, feed conversion, or egg quality were detected. Layer feed consumption was significantly greater among birds beak trimmed at 10 d than among those trimmed at 10 and 84 d. Most of the effects associated with beak trimming treatments can be attributed to the influence that beak trimming had on feed consumption. PMID- 7792232 TI - Effects of feeding nivalenol-contaminated diets to male broiler chickens. AB - In two feeding trials the effect of nivalenol (NIV) on male broiler chickens was studied. A commercial starter diet was provided for ad libitum consumption throughout the whole experiment. The NIV was added to the feed when the birds were 7 d old. Growth and feed consumption were thereafter registered every 5th d during 20 d. In the first trial birds were offered feed containing 0, .5, 2.5, or 5 ppm NIV. The only variable that significantly differed from the control was the concentration of uric acid in plasma, which was increased by 94 and 66%, respectively, in treatment groups 2.5 and 5 ppm. In the second trial, NIV concentrations of 0, 3, 6, and 12 ppm were used. The weight gain for the 20-d period was decreased by 11% with 6 and 12 ppm. During this period these birds showed a decrease of about 6% in feed consumption and feed conversion efficiency. Gizzard erosions were found in 33% of the birds fed 12 ppm NIV and in 8% of those fed 3 or 6 ppm. No such erosions were found in the control birds. Relatively, the liver weights in the 12 ppm group were reduced more than total body weights. No effects on relative organ weights were found when bursa, spleen, and gizzard were compared to control. In the blood, no change compared to control was found in hematocrit or in the plasma concentration of glucose, calcium, cholesterol, triglycerides, and uric acid, or in the plasma activity of aspartate amino transferase, alanine amino transferase, or gamma glutamyl transpeptidase. PMID- 7792233 TI - Influence of a hydrated sodium calcium aluminosilicate and virginiamycin on aflatoxicosis in broiler chicks. AB - Male broiler chicks were fed diets containing 0 or 3.5 mg aflatoxin (AF)/kg from 1 to 28 d of age. The diets were amended with either .5% hydrated sodium calcium aluminosilicate (HSCAS), 16.5 mg virginiamycin (VM)/kg of diet, or .5% HSCAS + 16.5 mg VM/kg of diet to determine the effects of these compounds during aflatoxicosis. When compared with controls (814 g), BW gains were significantly lower for broilers fed the AF (731 g) or AF+VM (716 g) diets. No differences were found between the BW gains of chicks fed diets without aflatoxin (814 g) and those of chicks fed AF+HSCAS (793 g) or AF+HSCAS+VM (803 g), indicating approximately 75% protection against decreased BW gain by HSCAS and 87% protection by the HSCAS+VM combination. Relative weights of the liver and kidney and creatine kinase activity were significantly increased and albumin, total protein, cholesterol, uric acid, and inorganic phosphorus concentrations were decreased in chicks fed the diet containing AF alone. With the exception of albumin, HSCAS was effective in restoring these values to control values. The findings of this research suggest that HSCAS and HSCAS+VM can counteract some of the toxic effects of AF in growing broiler chicks. PMID- 7792235 TI - Observations on disinfection regimens used on Salmonella enteritidis infected poultry units. AB - Studies carried out at the laboratory and in the field identified many potential problems during disinfection of poultry units naturally contaminated with Salmonella enteritidis. There appeared to be variations in the efficiency of commonly used disinfectants within a disinfectant group when used in a contaminated house. It was possible for Salmonella and other coliforms to be amplified during the pressure washing or steam cleaning process. If an effective terminal disinfectant was not used after this, then high levels of Salmonella were likely to persist. The efficiency of the disinfection regimen was not directly dependent on the standard of physical cleaning if this was carried out to a reasonable standard, as a high level of elimination of Salmonella could be achieved even in the presence of substantial quantities of residual organic matter. Disinfection regimens involving formaldehyde, either as part of a terminal compound disinfectant spray or as a final fogging agent, were found to be the most effective in the field. PMID- 7792234 TI - Effects of cage population on the productive performance of layers. AB - Two commercial layer strains (3,456 hens total) were used to examine the effects of bird population on productive performance. Four cage population sizes (6, 8, 12, and 24 birds per cage) were compared. All cages were 35.7 cm deep and varied in width (61.2, 81.6, 122.4, and 244.8 cm). Floor space per bird was 364.1 cm2 and feeder space per bird was 10.2 cm in each cage configuration. Egg production and egg quality were measured from 20 to 72 wk of age. Strain differences were detected in hen-day egg production, egg mass, feed consumption, cracked egg percentage, Grade A eggs, Grade B eggs, peewee eggs, and large egg yield. There were no interactions between strain and cage population size. Cage population had no influence on hen-day egg production, mortality, feed conversion, egg size (peewee, small, medium, large, extra large), egg mass, lost eggs (by meat or blood spots), and percentage Grade B eggs. Percentage Grade A eggs, cracked egg percentage, and feed consumption were significantly influenced by cage population size. Hens housed at eight birds per cage had a greater percentage of Grade A eggs and a lower percentage of cracked eggs than those at other populations. Feed consumption was significantly greater for hens housed at 12 and 24 birds per cage compared with those at 6 and 8 birds per cage, respectively. PMID- 7792236 TI - Polyacrylamide gel electrophoretic patterns of chicken serum in acute inflammation induced by intramuscular injection of turpentine. AB - To develop a method to detect hidden inflammation using serum protein in chickens, changes in serum proteins with acute inflammation were analyzed using a turpentine-induced inflammation model. Inflammation in the pectoral muscle of a 14-wk-old White Leghorn became apparent 3 h after the injection of turpentine and became more severe thereafter. Coincident with the development of inflammation, changes in serum proteins were analyzed by electrophoresis on polyacrylamide gradient gels. The electrophoretic patterns were divided into 21 segments. Two of these segments increased remarkably. These were located near the center of the electrophoretic pattern and were identified as transferrin due to iron staining, correlation of movement against a commercial transferrin sample in SDS-PAGE, and immunoblotting. These results suggest that transferrin may serve as a marker for inflammation in chicken. PMID- 7792237 TI - Response to Salmonella enteritidis infection by the immunocompromised avian host. AB - To develop knowledge of the avian immune response and improve the ability of chickens to resist infection by Salmonella enteritidis (SE), the role of the different components of the immune response against SE infection was examined. Birds were given treatments with cyclophosphamide, cyclosporine A, or testosterone propionate to induce immunological deficiency, and experiments were performed to determine the effects of each on the immune response. Each treatment reduced hatch rate, survival rate, and rate of weight gain. As measured by flow cytometry, treatments with cyclophosphamide and testosterone propionate decreased the percentages of B cells to background levels and increased the percentages of CT8 cells significantly above controls. The intestinal shed rate of SE increased after treatment with testosterone propionate and cyclophosphamide, but dissemination to the spleen of infected birds was not different from controls for any treatment. The SE infection was also immunosuppressive as measured by the proliferative response to mitogenic stimulation. Maximum lymphocyte proliferation occurred 1 wk after infection in response to .5 micrograms concanavalin A per 10(6) cells. By the 2nd wk, proliferation dropped 10-fold to almost no response. Results showed that immunocompetence relied on interdependent functions of multiple components of the immune response, i.e., aspects of both humoral and cell-mediated immunity. PMID- 7792238 TI - Vitamin E in viral inactivated vaccines. AB - This research aimed at verifying whether vitamin E added to inactivated and emulsified vaccines enhances the immune response to viral antigens in chicken. Three hundred and twenty broilers (males and females) and 16 types of vaccines, varying in viral antigen [Newcastle disease virus, egg drop syndrome 1976 virus (EDS76V), and infectious bursal disease virus] and vitamin E amount (replacing 10, 20, and 30% of mineral oil) were used. Results show that vaccines with vitamin E, especially when it replaces 20 or 30% of mineral oil, induces a more rapid and higher antibody response than control vaccines. An adjuvant effect of vitamin E was also present in viral vaccine lacking bacterial antigens. Apart from vitamin E content, the Newcastle disease virus and infectious bursal disease virus monovalent vaccines induced higher titers of specific circulating antibodies in birds than did trivalent vaccines. PMID- 7792239 TI - Effect of substituting sesame meal for soybean meal on layer and broiler performance. AB - Sesame meal (SM, 47.1% CP) has an amino acid composition similar to that of soybean meal (SBM, 47.7% CP) with the exception of lower lysine and higher methionine, but has been relatively underutilized in poultry feeds. Two experiments (1 and 2) were conducted to measure laying performance and hatchability of White Leghorn hens fed practical diets (17% CP), and two additional experiments (3 and 4) examined the performance of broiler chicks fed practical diets (22% CP) with varying substitution levels of screw-pressed SM for solvent-extracted SBM. In Experiment 1, SM contributed 0, 12.6, 25.3, 38, or 50.6% of dietary CP, and each diet was fed to hens for 6 wk. In Experiment 2, SM contributed 0, 4.7, 9.4, 14.1, 18.8, or 23.6% of dietary CP, and each diet was fed for 4 wk. In Experiment 3, SM contributed 0, 15, 30, 45, or 60% of dietary CP, and in Experiment 4, SM contributed 0, 38, or 76% of dietary CP; in these experiments, diets were fed to broiler chicks for 3 wk. There were no differences in egg production, egg weight, egg mass, daily feed intake, or body weight measurements among control hens fed SBM and hens fed SM at 12.6% (Experiment 1) or 4.7 to 18.8% of dietary CP (Experiment 2). Hens consuming these diets were able to satisfy their daily requirements for essential amino acids. Egg quality measurements were similar among hens fed the control SBM diet and those fed SM at 12.6 or 25.3% of dietary CP in Experiment 1, and at 4.7 to 23.6% of dietary CP in Experiment 2. All production variables were significantly depressed in hens that were fed SM at 38 or 50.6% of dietary CP, but Haugh units increased. In Experiment 3, the performance of broiler chicks fed the diet containing SM at 15% of dietary CP was not different from that of the control chicks fed the SBM diet, and both diets contained essential amino acids at required levels. Feed intake, body weight gain, and feed conversion were consistently depressed with increased SM substitution at 30, 45, or 60% of dietary CP. In Experiment 4, feed intake was not different between the control chicks fed the SBM diet and those fed the diet containing SM at 38% of dietary CP. However, body weight gain and feed conversion of chicks fed diets containing SM at 38 or 76% of dietary CP were significantly lower than those of the control chicks fed the SBM diet. PMID- 7792240 TI - Response of broiler breeders to low-protein diets. 1. Adult breeder performance. AB - Four hundred female and 50 male commercial strain breeders were reared separately from 1 d to 18 wk of age, with all birds receiving the same diet. At 18 wk, all pullets were weighed and the extreme weights removed from the group. The remaining hens were then randomly sorted into four treatment groups each represented by four replicate groups. Treatment involved feeding different levels of CP (16, 14, 12, and 10%), supplemented with synthetic lysine and methionine in order to maintain constant lysine and TSAA levels, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily. Dietary protein had no effect on egg production (P > .05). However, breeders fed 10% CP were lighter (P < .01) in weight than birds fed 16% CP. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01), and this resulted in reduced chick weight at hatching. Low-protein diets also resulted in less nitrogen excretion. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without affecting performance. PMID- 7792241 TI - Response of broiler breeders to low-protein diets. 2. Offspring performance. AB - Broiler breeders were allocated at random to one of four experimental diets containing various levels of CP (16, 14, 12, or 10%), at constant methionine+cystine and lysine levels of .59 and .82%, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily to 64 wk of age. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01) and in two trials involving breeders at 30 and 52 wk of age this resulted in reduced chick weight at hatching, although no lasting effect was observed on weight of offspring at 48 d. Better feed efficiency (P < .05) was observed from broilers hatched from hens fed lower CP diets. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without adversely affecting offspring performance. PMID- 7792242 TI - Relative biological availability of manganese from manganese proteinate, manganese sulfate, and manganese monoxide in broilers reared at elevated temperatures. AB - The relative biological availabilities of Mn from Mn proteinate, MnSO4, and MnO were compared under two different environmental conditions. Commercial broilers were reared in brooder batteries between Days 1 and 21 and fed diets containing 0, 1,000, 2,000, or 3,000 mg supplemental Mn/kg diet. On Day 22, birds were transferred to individual cages in two environmental chambers maintaining the same dietary Mn sources and supplemental levels. The temperature in one chamber cycled between 18 and 23.9 C (thermoneutral, TN), and in the other chamber cycled between 23.9 and 35 C (heat distress, HD). Birds in the HD environment were exposed to 8 h of 23.9 C, 4 h of 23.9 to 35 C, 4 h of 35 C, and 8 h of 35 to 23.9 C. Tibia Mn increased linearly (P < .05) with level of supplementation when measured on Days 22 and 47. Based on ratios of slopes from multiple linear regression analysis of bone Mn on Mn intake from various sources, the biological availabilities of Mn proteinate and MnO relative to MnSO4 (100%) were 120 and 91%, respectively, in 21-d-old chicks. In 49-d-old birds, corresponding relative biological availabilities of Mn from proteinate and oxide were 125 and 83%, respectively, in birds reared under TN, and 145 and 82%, respectively, for HD birds. PMID- 7792243 TI - Changes in pulmonary arterial and femoral arterial blood pressure upon acute exposure to hypobaric hypoxia in broiler chickens. AB - An experiment was conducted to investigate the pulmonary arterial and femoral arterial pressure responses to acute hypobaric hypoxia. Twenty-four, 7-wk-old Hubbard x Hubbard male chickens were lightly anesthetized and catheters were introduced into the right femoral artery and the pulmonary artery. The birds were then placed in a hypobaric chamber, and blood pressure responses were monitored during acute (15 min) exposures to simulated altitudes of 2,000 and 4,000 m. The pulmonary artery pressure increased .7 and 4% during the first and second exposures to a simulated altitude of 2,000 m, whereas the femoral artery pressure decreased 6 and 8% during exposures to this altitude. The pulmonary artery pressure increased 7% on the first exposure and 23% (P < .05) on the second exposure to a simulated altitude of 4,000 m. The femoral arterial pressure decreased (P < .05) on both exposures to this altitude (29 and 24%, respectively). The initial femoral and pulmonary artery pressures and changes in these pressures upon exposure to hypobaric hypoxia were not consistently correlated with the characteristics of the electrocardiogram, packed cell volume, body weight, or the right:total ventricular weight ratio. These results indicate that acute hypobaric hypoxia elicits a hypotensive response in the systemic arterial circulation and a hypertensive response in the pulmonary arterial circulation of broiler chickens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792244 TI - An opiate receptor in the neurohypophysis of laying hens. AB - An opiate binding component in the membrane fraction of the neurohypophysis of the laying hen showed a high affinity, limited capacity, reversible binding, and binding specificity to [3H]diprenorphine. The binding sites were of a single class. The equilibrium dissociation constant was .30 +/- .03 nM (mean +/- SEM; n = 5) in Scatchard analysis and .31 +/- .02 nM (n = 5) in kinetic analysis. The maximum binding capacity determined by Scatchard analysis was 619 +/- 34 fmol/mg protein (n = 5). The association and dissociation rate constants determined by kinetic analysis were .088 +/- .002 nM-1 min-1 (n = 5) and .027 +/- .001 min-1 (n = 5), respectively. The results suggest that the binding component is regarded as being an opiate receptor. PMID- 7792245 TI - The role of defeathering in the contamination of turkey skin by Salmonella species and Listeria monocytogenes. AB - This study was undertaken to determine whether the incidence of either Salmonella spp. or Listeria monocytogenes on turkeys at three commercial processors could be related to the type of defeathering system: 1) conventional, 58 C common bath scald; 2) kosher, 7 C common bath scald; or 3) steam-spray, 62 C nonimmersion scald. Flocks were sampled before defeathering, after defeathering, and after chill at each facility. The incidence of Salmonella-positive turkeys significantly increased subsequent to conventional defeathering (10 positive out of 14) as compared with before defeathering (3/14). The number of Salmonella positive carcasses following kosher (0/14) and steam-spray (2/14) defeathering were similar to the number of Salmonella-positive carcasses found prior to defeathering (1/14 and 3/14, respectively). The incidence of Salmonella-positive carcasses following chill was slightly lower, but not significantly different than the number of Salmonella-positive carcasses found immediately following defeathering at all processors (8/14, 0/14, 1/14 for conventional, kosher, and steam-spray processors, respectively). Although L. monocytogenes was detected on turkeys sampled before chilling (2/10, kosher) and after chilling (8/14, kosher; 1/14, conventional), no L. monocytogenes was detected on turkeys at any of the processors prior to the evisceration process. Flocks with high aerobic plate counts prior to processing were more likely to contain Salmonella-positive birds throughout processing. Aerobic plate counts of all flocks were similar after chill whether or not Salmonella spp. and L. monocytogenes were detected. PMID- 7792246 TI - Effect of type of defeathering system on Salmonella cross-contamination during commercial processing. AB - The cross-contamination effects of three commercial defeathering systems were compared using turkeys from a single Salmonella-positive flock (< or = 15% cloacal-positive). Single or "common" flocks were used to control flock-to-flock variability. Thirty birds were mechanically defeathered in each system as the first flock of the day and compared with 30 hand-defeathered (control) birds. Three trials, each using a different common flock, were completed. In Trial 1, the incidence of Salmonella-positive birds decreased following mechanical defeathering at all three processors. The incidence of Salmonella-positive carcasses in test flocks increased following steam-spray (approximately 100%) and kosher (approximately 50%) defeathering in Trials 2 and 3, whereas no increase in Salmonella-positive carcasses resulted from conventional defeathering. The decrease in the number of Salmonella-positive birds as a result of defeathering observed in Trial 1, as compared to increases observed in Trials 2 and 3, may be related to the selection of feather-contaminated (Trial 1) vs intestinal colonized (Trials 2 and 3) turkeys. Surface temperature of the carcasses and length of time required to defeather were monitored within each system. It is hypothesized that the increases in the number of Salmonella-positive birds following steam-spray and kosher defeathering in Trials 2 and 3 were a result of skin surface changes occurring during the defeathering process, which allowed increased adherence or entrapment of Salmonella spp. on or within remaining skin layers. PMID- 7792248 TI - Salmonella contamination in commercial eggs and an egg production facility. AB - Egg samples were collected from various stages of an egg processing operation and from the attached production facility. Salmonella was isolated from 72.0% of all samples collected from the laying house environment. Recovery of Salmonella from flush water, ventilation fan, egg belt, and egg collector samples were (positive samples/total samples collected): 2/2, 4/4, 16/22, and 14/22, respectively. Salmonella was found on 7 of the 90 eggshells sampled before processing and 1 of 90 eggshells sampled after processing, but Salmonella was not found in the 180 eggs analyzed for internal contamination following processing. The one eggshell found positive for Salmonella following processing was detected when the pH of wash water samples was lowest (10.19). The 60 isolates from production facilities included the following Salmonella serotypes: S. agona, S. typhimurium, S. infantis, S. derby, S. heidelberg, S. california, S. montevideo, S. mbandaka, and untypable. The 22 isolates obtained from eggshells prior to processing were serotyped as S. heidelberg and S. montevideo. All five isolates obtained from eggshells after processing were serotyped as S. heidelberg. These data suggest that although the shells of about 1% of commercial eggs are contaminated with Salmonella, contamination of the internal contents of eggs with Salmonella is a rare event. PMID- 7792247 TI - The effects of ultrapasteurization with and without homogenization on the chemical, physical, and functional properties of aseptically packaged liquid whole egg. AB - The effects of ultrapasteurization with and without homogenization on some chemical, physical, and functional properties of liquid whole egg were observed. Heat treatments of 64, 68, and 72 C each at 30, 60, and 95 s were conducted on liquid whole egg, unhomogenized and homogenized [10.34 mPa (1,500 psi)]. The viscosity of the egg increased with increased processing temperature, and unhomogenized egg was more viscous than homogenized egg. alpha-Amylase was inactivated at 68 C for 30 s. Although cake height was highly correlated to soluble protein content, this relationship did not hold for all time-temperature combinations. Due to homogenization effects on soluble protein results, soluble protein is not a reliable predictor of egg functionality when homogenization is used in the process. Homogenization had no effect on the population reduction of aerobic bacteria in all but three of the nine time-temperature combinations. PMID- 7792249 TI - Rudolf Buchheim Conference. Focus on Neuropharmacology. In commemoration of the 175th birthday of Rudolf Buchheim. Tartu, Estonia, May 21-23, 1995. Abstracts. PMID- 7792250 TI - N-CAM and N-cadherin are specifically expressed in xanthophores, but not in the other types of pigment cells, melanophores, and iridiphores. AB - Little is known about cell-cell communication in pigment cells, whereas a number of signalling molecules have been implicated to control their migration, differentiation, and proliferation. We set out to investigate the expression of cell adhesion molecules (CAMs) in the three different types of pigment cells in poikilotherms, Oryzias latipes and Xenopus laevis. In the present experiments, the expression of N-CAM and N-cadherin in the pigment cells in vitro was examined by immunocytochemistry. Melanophores and xanthophores were isolated and cultured from scales or skins, while iridophores were harvested from skins or peritoneum. The results showed that N-CAM and N-cadherin were specifically expressed in xanthophores, but not in melanophores or iridophores in both O. latipes and X. laevis. N-CAM and N-cadherin basically colocalized in the restricted regions of xanthophores, although the N-caderin-expressed region was broader than the N-CAM expressed region in the same cell. The incidence of N-cadherin expression was higher than that of N-CAM expression. N-CAM and N-cadherin were expressed at the tip or the base of dendrites, or at the edge between dendrites in dendritic xanthophores. N-CAM and N-cadherin usually localized in small and narrow regions of xanthophores. This distribution pattern was essentially similar in xanthophores with round morphology, which exhibited spot, band, or semicircular immunoreactive regions on the peripheral edge of the cells. The difference in the distribution of pigment granules within the cells, culture period, fixatives, or immunofluorescent markers used in the experiments did not alter the immunostaining pattern. PMID- 7792252 TI - A transmission electron microscopic (TEM) method for determining structural colors reflected by lizard iridophores. AB - Iridescent tissue colors are thought to be produced by iridophores through the optical phenomenon of thin-layer interference. Land and others have shown that structural features, predominantly reflecting platelet width and the cytoplasmic spacing between layers of platelets, determine the wavelength of light maximally reflected by this mechanism in iridophores. Some researchers have used interference microscopy to estimate these structural parameters, but the most direct measurement technique should be transmission electron microscopy (TEM). Transmission electron microscopy (TEM) has associated processing artifacts (particularly cytoplasmic shrinkage) that preclude direct measurement of ultrastructure, but if a number of assumptions are made, reflected wavelengths can be predicted. A thin-layer interference model and its associated assumptions were tested using TEM measurements of iridophores from several brightly colored tissues of each of three lizards (Sceloporus jarrovi, S. undulatus erythrocheilus, and S. magister). In all the instances examined when the contribution of the pigments present were accounted for, tissue color corresponded with predicted iridophore reflectances from the model. Finally, if the model and its assumptions are assumed to be correct, the amount of iridophore cytoplasmic shrinkage as a result of TEM processing can be calculated. PMID- 7792251 TI - Keratinocyte extracellular matrix-mediated regulation of normal human melanocyte functions. AB - Active roles of cell-cell interaction between melanocytes and neighboring keratinocytes for the regulation of melanocyte functions in the skin have been suggested. We examined substantial regulatory mechanisms of keratinocyte extracellular matrix (kECMs) for normal human melanocyte functions without direct cell-cell contact. We specially devised kECMs from proliferating or differentiating keratinocytes and further treated them with environmental stimulus ultraviolet B (UVB) for skin pigmentary system. Normal human melanocytes (NHM) were cultured on the various keratinocyte ECMs and initially the effects of the kECMs upon melanocyte morphology (dendrite formation and extension), growth, melanin production and expressions of pigmentation-associated protein (MEL-5) and proliferation-associated protein (proliferating cell nuclear antigen; PCNA/cyclin) were studied. Then we compared the effects of these cell-matrix interactions with those of direct melanocyte-keratinocyte, cell-cell contact in co-culture on melanocyte functions. Melanocytes cultured on any types of the kECMs that were tested significantly extended dendrites more than that on plastic cell culture dish without kECM (control). Melanocytes cultured on any types of the kECMs that were tested significantly extended dendrites more than that on plastic cell culture dish without kECM (control). Melanocytes cultured on the kECM prepared from UVB irradiated differentiating keratinocytes resulted in 219% increase in the number of dendrites. The growth of melanocytes on kECMs was also stimulated up to 280% of control. The kECM produced by proliferating keratinocytes had a more significant effect on the growth than kECM from differentiating keratinocytes. This melanocyte growth stimulating effect was decreased with kECM from UVB treated differentiating keratinocytes. The melanin content per melanocyte was constant on any of the kECMs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792253 TI - Changes in adrenergic innervation to chromatophores during prolonged background adaptation in the medaka, Oryzias latipes. AB - The pattern of adrenergic innervation to scale chromatophores of the wild-type medaka, Oryzias latipes, was examined by autoradiography with 3H-norepinephrine and found for the first time to be changed reversibly during prolonged background adaptation. In scales of the medaka, which was adapted to a black background for 10-15 days, a great number of melanophores and dense networks of varicose fibers were observed: many fibers built up a radial plexus around each melanophore. However, the dense distribution of varicose fibers disappeared with a decrease in the number of melanophores during long-term adaptation to a white background. As to the changes in the innervation pattern to amelanotic melanophores of the medaka, orange-red variety, a similar result was obtained. Although the increase in the number of leucophores was observed in the medaka adapted to a white background, no exact plexuses of labeled fibers were confirmed around leucophores. From these results, it is concluded that the density of chromatic nerve fibers changes in parallel with the variation of the number of melanophores during prolonged background adaptation. PMID- 7792254 TI - The identification and partial cloning by PCR of the gene for tyrosinase-related protein-1 in the Mexican axolotl. AB - The tyrosinase gene family is currently composed of three members, tyrosinase and two tyrosinase-related proteins, TRP-1 and TRP-2. These three gene products have all been found to act in the synthesis of melanin pigments with the enzyme tyrosinase catalyzing the initial rate-limiting steps. Thus far these genes have primarily been analyzed in higher vertebrates. We have used degenerate PCR primers to isolate a large fragment of an axolotl tyrosinase-related protein. Sequence analysis of the entire 1,057-bp fragment isolated indicates a high degree of similarity to the mouse TRP-1, the product of the brown locus. Phylogenetic analysis supports the conclusion that the fragment isolated corresponds to the axolotl TRP-1 homolog. This is the first TRP-1 gene to be identified in an amphibian species. PMID- 7792255 TI - Characterization of vitiligo antigens. AB - Patients with vitiligo have circulating antibodies directed in part to pigment cell antigens with MWs of approximately 90, 75, and 40-45 kDs. These antigens are denominated VIT 90, VIT 75, and VIT 40, respectively. To further characterize these "vitiligo" antigens, we examined their relation to antigens defined by a panel of 25 monoclonal antibodies (moab) to pigment cell antigens. We found by immunoprecipitation and SDS-PAGE analysis of 125I labelled, detergent soluble, human melanocyte macromolecules, that 24 (83%) of 29 patients with vitiligo had antibodies to one or more vitiligo antigens vs. 2 (7%) of 28 control individuals. Seventeen of the 25 moabs did not react with any labelled antigen in the same lysate. Of the remaining eight moabs, only four precipitated an antigen that co migrated with one of the vitiligo antigens. Moab TA99, HMSA-5, and TMH-1 (all directed to the 75 kD tyrosinase-related protein [TRP1]) co-migrated with VIT 75. Moab W6/32 (directed to class I HLA antigen) co-migrated with VIT 40. Immunodepletion studies with vitiligo antibodies selectively depleted the antigen defined by W6/32 but not the antigen defined by TA99 and HMSA-5, indicating that VIT 75 was not the 75 kD tyrosinase-related protein. The vitiligo antigens were easily labelled by the lactoperoxidase technique but poorly labelled with 35S methionine, suggesting they are expressed on the cell surface. These studies indicate that VIT 90 and VIT 75 differ from antigens defined by currently available moabs to pigment cell antigens. VIT 40 appears to share a cross reactive epitope, or be tightly bound to, class I HLA antigen. PMID- 7792257 TI - Protein, calcium, and iron content of wild and cultivated species of Echinochloa. AB - Two species of Echinochloa millets and their direct wild ancestor species were analyzed for proximate composition, and amino acid, calcium, and iron content. Additionally, lactate polyacrylamide gel electrophoresis (PAGE) was performed to separate and resolve prolamin polypeptide present in the wild and domesticated species. The protein, calcium, and iron content of the four species were comparable to or greater than in other major cereals. Calcium was higher in each of the wild species than their domesticated counterpart. Essential amino acid values for the three species analyzed were generally higher than the FAO/WHO standards, except for lysine. Densitometric analysis of lactate PAGE gels revealed that the domesticated species contained prolamin, polypeptides that were either absent or present in smaller amounts in the wild species. The results indicate a wide variation in the content of examined nutrients and suggest that there is opportunity for improvement in the nutritional value of the Echinochloa millets via selective crossbreeding of wild and domesticated species. PMID- 7792256 TI - Antimelanoma antibodies in swine with spontaneously regressing melanoma. AB - Sinclair swine provide a unique model for studying mechanisms of tumor regression because they are born with melanomas that spontaneously regress approximately 10 weeks after birth. To examine whether an antitumor immune response is present in these animals, and, if so, to study its relation to tumor regression, 38 sera specimens collected at different times from 13 swine born with melanomas were tested for melanoma antibodies by immunoprecipitation and SDS-PAGE analysis of 125I labelled swine melanoma macromolecules. Antibodies to melanoma were present in 13 (100%) of the swine versus 1 of 3 control swine. The antibodies were directed to antigens of approximately 45, 68-75, or 100 kDa. These antigens were also expressed on human melanomas and normal melanocytes but on only one of five unrelated tumors. The incidence and level of these antibodies increased with time. Antibodies to the 45, 68-75, and 100 kDa antigens were present in 36%, 55%, and 9%, respectively, of sera collected prior to 7 weeks of age, but in 80%, 100%, and 37% of sera collected between 7 and 20 weeks (P < 0.05). The rise in melanoma antibodies usually preceded or appeared together with tumor regression and loss of pigmentation. These findings indicate that Sinclair swine with melanomas have antibodies to antigens preferentially expressed on pigment cells, and support the hypothesis that the regression phenomenon and the vitiligo-like skin depigmentation result from immune responses to common antigens shared by normal and malignant swine pigment cells. PMID- 7792258 TI - Effect of Japanese mint (Mentha arvensis) oil as fumigant on nutritional quality of stored sorghum. AB - Japanese mint (Mentha arvensis) oil (JMO) can be used effectively as fumigant against Sitophilus oryzae in stored sorghum. The effect of JMO at a dose of 166 microliter/l of space on nutrient composition and protein quality was studied in infested and uninfested sorghum grains stored for 3 months. The results revealed non significant effect of JMO on gran moisture, total ash, crude fibre, crude fat, crude protein and fat acidity in infested and uninfested grains at the end of 3 months storage. The JMO treatment had small but significant effect on reducing and non-reducing sugars. The values of Protein Efficiency Ratio (PER) for uninfested JMO treated grains, infested JMO treated grains and for untreated control stored for 3 months were 1.11, 1.07 and 1.09, respectively against control casein diet for which it was 2.15. PMID- 7792259 TI - Nutritional value and content of antinutritional compounds and toxics in ten wild legumes of Yucatan Peninsula. AB - The chemical and toxicological composition of ten wild legumes collected in Yucatan, Mexico was determined. For each species the whole fruit, (seed and pod), were studied as well as the seed and pod separately. A higher protein content was found in the seeds of A. lebbeck and P. saman (37.07 and 37.60% respectively). In the seeds of L. longystilus, C. yucatanensis and P. keyense a high concentration of fat was found, especially in the first with 31.34%. A high quantity of fiber was found in the pods. In general, the samples were rich in lysine (especially seeds) and scant in sulfur amino acids and tryptophan. All the samples showed high concentration of potassium and calcium. Some of them exhibited significant concentrations of iron. The pods of P. saman and P. keyense showed a high content of lectins. In the seeds of C. yucatanensis and in the pod of P. keyense high concentrations of trypsin inhibitors were found 60 and 406.7 TUI/mg sample respectively. The presence of saponins, was detected in seven samples, of which the seed of P. keyense had the highest concentration. Alkaloids were found only in the whole fruit and pod of P. saman and cyanogenic glucosides were present in A. pennatula. In general terms, the whole legume showed better digestibility than the pods alone. PMID- 7792260 TI - Effect of home processing on ascorbic acid and beta-carotene content of spinach (Spinacia oleracia) and amaranth (Amaranthus tricolor) leaves. AB - The present investigation was conducted to study the concentration of ascorbic acid and beta-carotene in spinach and amaranth leaves as affected by various domestic processing and cooking methods which included storage of leaves in polythene bags or without packing for 24 and 48 hours in refrigerator at 5 degrees C; at 30 degrees C in polythene bags; drying (sun and oven); blanching (5, 10, 15 min); open pan and pressure cooking. Ascorbic acid content of fresh leaves was 624.1 to 629.0 mg and beta-carotene content was 35.3 to 53.1 mg/100 g dry weight. The percent loss of ascorbic acid ranged from 1.1 to 6.3 and 55.3 to 65.9 while lower losses (0.0 to 1.3 and 1.5 to 2.1) of beta-carotene were observed in leaves stored in refrigerator and at 30 degrees C, respectively. A markedly greater reduction in ascorbic acid and beta-carotene was observed in dried, blanched and cooked leaves. The study recommended the storage of leaves in refrigerator, drying in oven, blanching for shorter time and cooking in pressure cooker for better retention of these two vitamins. PMID- 7792261 TI - Composition of sulfited potatoes: comparison with fresh and frozen potatoes. AB - The content in moisture, fat, protein, carbohydrate, fibre and vitamin C was analyzed in three commercial types of potatoes: sulfited (treated with E223), frozen potatoes (pre-fried) and fresh potatoes (not processed). The composition of sulfited potatoes does not usually appear in food composition tables. Our results showed significant differences in the content of carbohydrates and fibre between sulfited and fresh potatoes. The content of vitamin C in sulfited potatoes, which is similar to that of frozen potatoes, was shown to be approximately half of that found in fresh potatoes. PMID- 7792262 TI - Nutritional evaluation of the soy-whey milk analog La colina. AB - The milk analog La colina is a product which contains mainly whey, soy protein isolate and vegetable oil, designed for infants since one year, children, adolescents and adults of all ages. The concept behind this product is to offer an alternative to milk consumption which during the last decade has decreased dramatically in Venezuela mainly due to its high price and low availability. Accordingly, the purpose of this study was to evaluate nutritionally this new product in order to determine if from a nutritional stand point it could represent a valid alternative to milk consumption. The results showed that La Colina offers the same amount of protein, energy, vitamin A, calcium, phosphorus and potassium as whole milk powder and more sodium, iron and zinc. In addition, a rat assay showed that the energy in these two products is equally available and even though the proteins in La colina are 3.9% less digestible, their quality determined by growth, PER or the nitrogen retained are excellent and identical to the quality of the proteins in milk. These results agreed with the theoretical chemical score of the proteins of this new product, which indicated that the amino acid profile of the mixture can fulfill the amino acid requirements of children, adolescents an adults. Both milk and La colina are products with a high fat content. The fat in this new product however, is vegetable oil and therefore it has a more convenient fatty acid profile than whole milk and about one third of its cholesterol. In short, these results showed that La Colina from a nutritional point of view is an excellent alternative to milk consumption. PMID- 7792263 TI - The effect of Cd2+ on lipid components of sunflower (Helianthus annuus L.) seeds. AB - The effect of seven levels of Cd2+ viz. 0, 10, 20, 30, 40, 60 and 80 ppm (micrograms/g soil) supplied as cadmium chloride, on lipid components of sunflower seeds was studied in a pot experiment. The total and neutral lipids decreased while polar lipids (phospho and glycolipids) increased with the increasing levels of Cd2+. Oleic acid and linoleic acids were the major fatty acids in the total, polar and neutral lipid fractions. Oleic acid generally increased while linoleic acid decreased in all the lipid fractions with Cd2+ levels. The neutral lipid fraction had higher levels of palmitic, palmitoleic, stearic and oleic acid as compared to the total and polar lipid fractions. The plant dry weight and seed yield decreased whereas cadmium concentration in seeds increased consistently with increasing Cd2+ levels. PMID- 7792264 TI - Influence of growth conditions on the value of crisphead lettuce. 4. Quality changes during storage. AB - Crisphead lettuce (Lactuca sativa L. var capitata cvs. Marius and Saladin) were grown with a nitrogen supply from 50 to 200 kg N/hectare. Heads were stored for one or two weeks at 1 degree C in cold storage or ice bank cooling. Samples were taken for measurement of dry matter, sugars, vitamin C and nitrate. The content of dry matter, sugars (glucose, fructose) and vitamin C decreased with increasing level of nitrogen, and the content of nitrate increased. Except for nitrate the contents of the other quality attributes decreased at all nitrogen supply levels during storage. No differences were found between the storage systems, and beside fructose no significant differences were found between the two cultivars. The content of dry matter, vitamin C, and nitrate decreased from the outer to the inner head fraction, while the content of sugars increased. Trimming decreased the content of dry matter, vitamin C and nitrate and increased the content of sugars. To obtain heads from storage with a relatively high content of dry matter, sugars and vitamin C, and a relatively low content of nitrate the nitrogen supply must be as low as possible. Except for nitrate where no distinct results were found in this experiment it must also be recommended to store the heads as short time as possible. Possibly the cv. Saladin has some advantage quality attributes after storage compared with the cv. Marius. PMID- 7792265 TI - Variability in phytic acid content and protein digestibility of grain legumes. AB - Several genotypes, number given within parenthesis, of chickpea, pigeonpea, urd bean, mung bean and soybean, differing in seed characteristics were analyzed for phytic acid, in vitro protein digestibility (IVPD), protein, total phosphorus, and seed size. Phytic acid contents and IVPD values differed significantly among and within these species. Phytic acid content (mg/g) was the highest in soybean (36.4) followed by urd bean (13.7), pigeonpea (12.7), mung bean (12.0) and chickpea (9.6). On an average, phytic acid constituted 78.2 percent of the total phosphorus content and this percentage figure was the highest in soybean and the lowest in mung bean. In vitro protein digestibility (IVPD) of pigeonpea and chickpea genotypes varied from 60.4 to 74.4 percent and 65.3 to 79.4 percent, respectively. The IVPD values of genotypes of mung bean, urd bean and soybean ranged from 67.2 to 72.2 percent, 55.7 to 63.3 percent and 62.7 to 71.6 percent, respectively. There was a significant negative correlation between phytic acid and IVPD of these genotypes. Phytic acid was significantly and positively correlated with protein but the magnitude of correlation was very low in chickpea and pigeonpea. Results indicate that the genotypes of pulses with low phytic acid content could be identified and used in breeding program to improve their nutritive value and utilization. PMID- 7792266 TI - Improvement in HC1-extractability of minerals in home made weaning foods. AB - Three weaning foods were formulated from locally available cereals and pulses such as rice (Oryza sativa), kangini (Setaria italica), sanwak (Echinochloa frumentacea), green gram (Vigna radiata) and jaggery. Cereals and pulses were mixed in the proportion of 7:3. Nutrient composition of developed weaning foods was within range prescribed by Indian Standard Institute and was found to be acceptable. Roasting was the processing technique employed in developing weaning foods which resulted in significant increase in HC1-extractable minerals, an index of their bioavailability to humans. The higher HC1-extractability of the minerals may be ascribed to the decreased phytic acid in the processed home made weaning foods. PMID- 7792268 TI - [Macroscopic and microscopic heart preparation in ischemic heart diseases]. AB - The quality of the morphological analysis of myocardial and coronary alterations depends essentially on the method chosen for the heart dissection. Even if previous postmortem coronary angioplasty is not feasible, the best results are obtained by transverse sectioning of the ventricles in a bread-loaf fashion subsequent to formalin-fixation and serial cross-sectioning of the coronary arteries, with decalcification in addition if necessary. The distribution pattern of disseminated myocardial necrosis, the longitudinal, circumferential and transmural extent of infarction, its age and sequelae and its correlation to the coronary supplying areas can be evaluated with better accuracy than by dissecting the heart chambers according to the flow of blood. Cross-sectioning of coronary arteries with preservation of their luminal shape allows proper examination of the degree and extent of luminal narrowing, plaque hemorrhage, parietal and occluding thrombi and the effects and complications of angioplastic procedures or bypass surgery. Transverse sectioning of the heart is a prerequisite for adequate examination following sudden cardiac death and short-term territorial ischemia. Full-thickness samples of the ventricular walls, taken systematically with respect to coronary narrowing and coronary supplying areas, enable identification of early myocardial damage. PMID- 7792267 TI - Comparative study of the chemical composition of wild and cultivated beans (Phaseolus vulgaris). AB - Five wild Phaseolus vulgaris beans were compared with five cultivated Phaseolus vulgaris beans in proximate composition, total (true) protein, amino acid composition, and toxic and antinutritional factors. The wild beans contained more protein (25.5% vs. 21.7%), ash (5.15 vs. 4.15%), crude fiber (7.08% vs. 5.04%) compared to cultivated beans while the former contained less fat (0.56 vs. 0.89%) and carbohydrates (61.64 vs. 68.05%). Sulfur amino acids were found to be limiting in both groups of bean as expected; however, the cultivated beans had a higher content of the limiting amino acids. Therefore, the cultivated beans showed a better amino acid profile than the wild beans. Toxic factors were not found in either type of bean; the determinations included saponins, alkaloids, and cyanogenic glycosides. The antinutritional factors investigated were hemagglutinins (lectins) and trypsin inhibitors. The wild beans presented a higher content of trypsin inhibitors (28 TUI per mg) and lectins (9.6) than the cultivated beans did (21 TUI per mg and 7 respectively). From the chemical point of view, domestication seems to be positive; however, the better protein nutritive quality of the cultivated beans should be further confirmed by biological assays. PMID- 7792269 TI - [Cytokines and hematopoiesis]. AB - In hematopoiesis, regulation and differentiation present a very complex functional network in which multiple factors of the microenvironment are involved. In addition to direct cell-to-cell contacts and the modifying influences of the intercellular matrix, soluble mediators play an important role in intercellular communication. Cytokines exert their effects by binding with specific receptors that transfer their signals to individual cells. A common structure shared by subunits of these receptors leads to competitive inhibition in binding the cytokines with different affinity. By this mechanism specificity is reduced, on the one hand; however, on the other the complexity of interactions in the bone marrow is enhanced. A flood of in vitro and in vivo studies have established the impact of various cytokines on single hematopoietic cell lineages and their application for clinical use. However, there is a lack of knowledge concerning the cellular origin of the cytokines. According to the results of our studies elements of the erythro- and megakaryopoiesis are the source of cytokines like IL-1 alpha, IL-3, IL-6, and GM-CSF. PMID- 7792270 TI - [Analysis of inflammatory reaction and epithelial proliferation in corpus mucosa of the stomach. A contribution to carcinogenesis]. AB - To elucidate conflicting evidence concerning the role of Helicobacter pylori (HP) in the evolution of gastric carcinoma, a retrospective analysis was performed on the corpus mucosa of gastric surgical specimens removed from patients with gastric carcinoma (n = 53) and pancreatic carcinoma (n = 45). Prevalence, activity and degree of chronic active gastritis (CAG) were investigated. Furthermore, proliferative activity was determined by the expression of the Ki67 antigen in epithelial cells of the neck region and the foveolae using immunohistochemistry. CAG and intestinal metaplasia were significantly more prevalent in patients with gastric than with pancreatic neoplasms. Degree and activity of CAG were higher in the group of patients with gastric carcinomas. Numbers of Ki67-positive nuclei were significantly higher in pronounced than in mild CAG. Our data are in keeping with the assumption that HP-associated CAG contributes to the development of gastric adenocarcinoma. As possible pathomechanism, it may be assumed that a conspicuously expressed inflammatory reaction triggers epithelial proliferation, with resulting higher vulnerability to mutagenic effects. PMID- 7792271 TI - [Value of monoclonal antibodies (PC 10, MIB1, p53 and LeuM 1) for assessing the prognosis of patients with squamous epithelial carcinoma of the larynx after partial laser resection]. AB - An immunohistochemical analysis with monoclonal antibodies against Ki-67 (MIB 1), PCNA (PC10), p53 and Lewis X antigen was performed on 47 squamous carcinomas of the larynx after partial laser resection. Ki-67 index and expression of Lewis X antigen correlated significantly with both tumor recurrence rate and tumor-free interval. A much weaker relationship was found for the expression of proliferating cell nuclear antigen (PCNA), and no correlation existed with p53 expression. In conclusion, examination of Ki-67 and Lewis X antigen is thought to provide useful prognostic information concerning laser-resectable squamous carcinomas of the larynx. PMID- 7792272 TI - [Initial studies of the prevalence of human Herpesvirus 7 (HHV-7) in Mexican blood donors]. AB - Human herpesvirus 7 (HHV-7) has been recently isolated from CD4-positive peripheral blood lymphocytes of a healthy person. The present study was performed to find the antibody prevalence of this virus in the healthy Mexican population. Two hundred blood samples from candidates for blood donation at the General Hospital of Mexico were studied with the indirect immunofluorescence test (IFA) in HHV-7 infected SupT1 cells. 83.5% were male persons and 16.5% female, the mean age for the male group was 28.8 years and for the female group 31.5. The donors came from 12 different states in Mexico, predominantly from the city (60.8%), and had different occupations. Almost all samples (98.5%) were positive to HHV-7. Other studies done revealed 1% positive to brucella, 1% positive to Hepatitis B, 2% positive to syphilis, hepatitis C and HIV test were negative in the whole group studied. There was a high incidence of HHV-7 in the group studied: more than 50% of the subject had high titers. This results should be further studied determine titers indicative of an active infection and to search for any association with illnesses. PMID- 7792273 TI - [Apoptosis in Hodgkin's disease]. AB - Previous studies have concentrated on the proliferative behaviour of the neoplastic cell compartment in Hodgkin's disease (HD). The aim of the current investigation was to analyse the frequency of programmed cell deaths in Hodgkin and Reed-Sternberg (HRS) cells in the different subtypes of HD and to correlate this phenomenon with the expression of the bcl-2 oncogene. For this purpose, we investigated paraffin-embedded material from 63 cases of HD. Oncogene expression was determined by immunohistochemistry with the monoclonal antibody bcl-2-124. The detection of apoptotic cells was facilitated by application of the in situ end-labelling (ISEL) technique. Our results confirmed that bcl-2 expression is low in the lymphocyte-predominant subtype of HD. Apoptotic cells were found in all subtypes to a variable extent and were not significantly associated with any particular subtype. Interestingly, there was no correlation of bcl-2 expression and the presence or absence of apoptotic HRS cells. Hence, other factors must be operative in the regulation of programmed cell death in HD. Such mechanisms have been described for lymphocytes under various conditions, such as negative selection in germinal centres and within the thymus, DNA damage due to irradiation, and cellular cytotoxicity. PMID- 7792274 TI - [Small cell bronchial carcinoma following chemotherapy. Morphological findings]. AB - Resection specimens of 14 patients with small cell bronchial carcinoma after neoadjuvant chemotherapy were processed histologically and graded according to a three-step regression grading system: grade I, no or only slight tumor regression; grade II, incomplete tumor regression; grade III, complete tumor regression without vital tumor tissue. In five patients with either no vital tumor tissue or only small tumor remnants in the resection samples, a typical sequence of central fresh tumor necrosis, foam cell rim, vascular granulation tissue and peripheral scar formation was seen. This morphological finding may be interpreted as a characteristic, but unspecific parameter of good response to preoperative chemotherapy. The presence of vital tumor rims surrounding the capillary bed with intermingled necrotic foci, however, argues in favor of spontaneous tumor regression, which is commonly observed in small cell lung cancer. PMID- 7792275 TI - [Extraneural metastasis of brain and spinal cord tumors. Report of 2 cases]. AB - This case report refers to two patients with the rare entity of an extraneural metastasizing central nervous system tumor. The first patient presented with ipsilateral cervical lymph node metastases 4 years after a diagnostic biopsy and 2 years after removal of an anaplastic oligodendroglioma, respectively. The origin of the metastases was confirmed by immunohistochemistry. The second case described was found in a 26-year-old female who had suffered from a spinal cord pilocytic astrocytoma in infancy and been treated by surgery and radiotherapy. On postmortem examination, transformation to a primitive neuroectodermal tumor was found. Morphological and immunohistochemical features of the metastases were exactly identical with those of the primary tumors in both cases. The pathomechanisms of metastasizing CNS tumors are discussed with reference to the reasons why such cases are so rarely observed. The incidence of remote metastases and differences depending on tumor type are estimated. No relation to malignancy grade can be detected. PMID- 7792276 TI - [Bilateral breast carcinoma after recurrent myxoid liposarcoma of the breast]. AB - The case is presented of a 26-year-old woman with myxoid liposarcoma of the right breast who developed a relapse with anaplastic spindle-cell mesenchymal tumor 7 months after primary therapy. Additionally, 13 months later a bilateral adeno carcinoma of differing histological grade occurred in the breasts. To the best of our knowledge, no comparable sarcoma-carcinoma sequence in the mammary gland has been reported. For this reason this case is discussed, with special emphasis on possible causative factors and the relationship to the Li-Fraumeni syndrome. PMID- 7792277 TI - Mechanisms of the fetomaternal transfer of Na+ across the dually perfused placenta of the rat. AB - In order to investigate mechanisms of fetal-maternal (F-M) transfer of Na+, clearance of 22Na+ and 51Cr-EDTA was measured simultaneously across the dually perfused placenta of the rat. In eight experiments clearance was measured successively in the F-M (Kfm) and in the maternal-fetal (M-F; Kmf) directions. Clearance of 22Na+ in the two directions was approximately equal (Kmf = 11.6 +/- 2.0 microliters/min; Kfm = 11.1 +/- 1.7 microliters/min: mean +/- s.d.) while Kfm of 51Cr-EDTA (4.4 +/- 0.7 microliters/min) was nearly double Kmf (2.4 +/- 0.8 microliters/min) for this tracer. Even greater asymmetry in the transfer of 51Cr EDTA was found when measured across intact (non-perfused) placenta. It is suggested that this asymmetry is caused by volume flow in the F-M direction. In other experiments transfer was measured in the F-M direction only. Ouabain (0.1 mM) on the maternal side and reduced concentration of Na+ (25 mM) on the fetal side had no effect on the F-M transfer of the tracers. Reducing the temperature of the preparation by 5 degrees C significantly decreased transfer of 22Na+. The transfer of 22Na was inversely related to the concentration of K+ on the fetal side. These observations suggest that the F-M transfer of Na+ has three components: diffusion through paracellular routes; convective flow by filtration through wide placental pores, and transcellular transport by a mechanism which is uncertain at present. PMID- 7792278 TI - Cellular localization of corticotrophin releasing hormone in the human placenta, fetal membranes and decidua. AB - Corticotrophin releasing hormone (CRH), is produced by the human placenta, fetal membranes and decidua and has been detected in maternal and fetal plasma and amniotic fluid during human pregnancy. Previous studies of the cellular localization of CRH in the placenta and fetal membranes have yielded conflicting results. In this study, placentae were obtained from uncomplicated pregnancies immediately after elective termination or after normal delivery at term. Zamboni's fixed sections of villi and membrane-decidua, were cut at 10 microns by cryostat and immunocytochemistry was performed using an anti-rat/human CRH antiserum. In first and second trimester placentae, the amount of CRH reaction product present was variable. CRH was localized in both the syncytiotrophoblast and cytotrophoblast in first and second trimester tissue. In term placentae, CRH was identified consistently in the syncytiotrophoblast. In addition, strong CRH reaction was localized to the amnion epithelium of the fetal membranes. Positive immunoreactivity was also detected in the chorion and decidua although at a lower level of intensity. In trophoblast cells and in the amnion epithelium, CRH reaction product was contained in distinct granules. The regulation of CRH and its physiological role may differ in these diverse cell types. Possible effects of CRH include autocrine or paracrine actions within the amnion, chorion and decidua while CRH derived from syncytiotrophoblast may have endocrine effects through access to the maternal and fetal circulations. PMID- 7792279 TI - Maternal plasma and placental immunoreactive corticotrophin-releasing factor concentrations in infection-associated term and pre-term delivery. AB - The present study aimed to investigate whether microbial invasion of the amniotic cavity affects maternal plasma or placental immunoreactive corticotrophin releasing factor (ir-CRF) concentrations in pregnant women with pre-term or term labour. A cross-sectional study was conducted collecting blood samples in: (1) women with pre-term labour and intact membranes (25-36 weeks), with or without microbial invasion of the amniotic cavity (subdivided into three groups: 1A, no microbial invasion of the amniotic cavity, delivery at term, n = 54; group 1B, delivery < 48 h, no microbial invasion of the amniotic cavity, n = 10; group 1C, delivery < 48 h, microbial invasion of the amniotic cavity, n = 8); (2) women at term, not in labour and without microbial invasion of the amniotic cavity (n = 15); (3) women in spontaneous active labour at term without (A) (n = 55) or with (B) (n = 16) microbial invasion of the amniotic cavity; and (4) healthy women not in labour at 25-36 weeks of gestation (n = 25). Specimens of trophoblast tissue were collected from pregnant women with pre-term labour (no microbial invasion of the amniotic cavity, n = 6; microbial invasion of the amniotic cavity, n = 4) or delivering at term (no microbial invasion of the amniotic cavity, n = 8; microbial invasion of the amniotic cavity, n = 4). A specific radioimmunoassay on acidic extracts of plasma or placental specimens was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792280 TI - Chronic reduction in fetal blood flow is associated with placental infarction. AB - The placenta receives two arterial blood supplies, i.e. one maternal and one fetal. It has been suggested that placental infarction should occur only if both blood supplies are compromised (Wigglesworth, 1984). This hypothesis has not been tested. Haemosiderosis of the trophoblast basement membrane (TBMH) has recently been identified as a feature of fetal artery thrombosis and suggested as a marker of impaired fetal blood flow which is identifiable in both viable and necrotic tissue. We examined 50 placental infarcts for evidence of TBMH, both grossly and microscopically. These were compared with four types of control tissue. Eleven placentae from cases of prolonged intrauterine death, in which this feature was first described, and 35 fetal artery thromboses were used as positive controls and 20 placentae from uncomplicated pregnancies were available as negative controls. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Microscopically, 36 per cent of infarcts showed TBMH in at least 5 per cent of villi within the lesion and 60 per cent of infarcts showed at least one cluster of villi with the feature. These findings point to a disturbance in fetal blood flow intimately associated with but pre-dating the placental infarction. These findings represent the first experimental evidence to support Wigglesworth's theory and suggest that reduction in fetal blood flow prior to thrombosis of maternal vessels contributes to the pathophysiology of placental infarction. PMID- 7792281 TI - The effects of maternal aerobic exercise on human placental development: placental volumetric composition and surface areas. AB - The histomorphometry of term placentae from women who exercised regularly throughout either the first half or all of pregnancy was compared to that of placentae from matched controls to determine if regular exercise during pregnancy produced histomorphometric evidence of altered development and transport capacity. Conventional stereological techniques were used to estimate placental volumetric composition, surface areas, and villous and vascular configurations in the three groups. Exercise confined to early pregnancy increased the parenchymal component of the placenta, total vascular volume and site-specific capillary volume and surface area. Exercise throughout pregnancy increased these and multiple other histomorphometric parameters associated with the rate of placental perfusion and transfer function. However, significant changes were confined to villi > 80 microns in diameter. The localization of both the timing of the stimulus and the anatomical sites affected indicates that regular, sustained exercise modifies placental development primarily in early and mid-pregnancy. We speculate that the lack of significant changes in the structure and configuration of the smaller villi indicates that other adaptive mechanisms, such as increased rates of placental blood flow, must be well developed by the latter portion of the mid-trimester and adequately maintain fetal oxygenation and substrate delivery throughout the third trimester. PMID- 7792282 TI - Cytokines in the viviparous reproduction of squamate reptiles: interleukin-1 alpha (IL-1 alpha) and IL-1 beta in placental structures of a skink. AB - Placental viviparity is known in many species of squamate reptiles. Among these, some scincids have developed an epithelio-chorial chorio-allantoic placenta which in the structure of its central ridged zone is similar to those of certain therian mammalian species. A broad range of immunoregulatory peptides, cytokines, has been identified at the maternofetal interface of several species of mammals, either with invasive or non-invasive types of placenta. Thus we began to study whether interleukin-1, which is considered to play a crucial role in mammalian pregnancy, might also be involved in the viviparity of reptilian species. Placentae of Chalcides chalcides L. were processed by immunohistochemistry and incubated in a culture medium for different times. A very strong immunoreactivity for interleukin-1 alpha (IL-1 alpha) and for interleukin-1 beta (IL-1 beta) was present in the chorial epiblast and in uterine epithelial cells, with varying degree and localization in different periods of pregnancy. IL-1 beta was also released into the medium at different amounts during incubation. In light of the mammalian data, our results suggest that the role of cytokines in pregnancy may represent a significant event in the evolution of placental viviparity. PMID- 7792283 TI - Characterization of the placental barrier to murine enterovirus infection. AB - We performed studies to characterize the mechanisms responsible for development during gestation of a placental barrier to Theiler's murine encephalomyelitis virus (TMEV) in a murine model of gestational enterovirus infection. Electron microscopy of placentae infected in early gestation revealed TMEV-induced changes in the decidua, giant cell, spongiotrophoblast, and labyrinth layers; in contrast, placentae infected in middle and late pregnancy demonstrated degenerative changes in the decidua, giant cell, and spongiotrophoblast layers but not in the labyrinth. Immunohistochemistry and in situ hybridization of placentae infected in early or late gestation demonstrated accumulation of monocytes/macrophages in infected, histologically damaged labyrinths, but no infiltration of immune cells into infected but histologically normal placental regions. Silver staining of placentae from dams inoculated in late gestation with inert gold beads the size of TMEV virions revealed beads within the decidua, giant cell, and spongiotrophoblast layers, but restriction of beads from labyrinths, similar to the usual distribution of TMEV in placentae infected in late pregnancy. These experiments suggest that anatomical relationships, and not systemic immune response, appear to be a major contributor to the murine placental barrier to TMEV. PMID- 7792284 TI - [Pilot project for evaluation of lung function reference values]. AB - Lung function tests were performed in this study on 139 adults (mean age 36 years), as well as on 91 female persons between 16 and 18 years of age (the latter just starting on their professional careers), the lungs being healthy in each case in both groups. The findings were compared with the currently accepted reference value formulae after Quanjer et al., and Zapletal as well as further developed reference value formulae after Brandli et al., Most of the measurement data obtained by spirometry for the BGFA group of probands are between the two recommended reference values for adults with better coincidence with Brandli's predictions (exceptions being MMEF25-75 MEF 50 and MEF 25). In our studies we obtained higher values than the reference median values after Quanjer and Zapletal for IVC, FVC, FEV1 and PEF by 6-8% and 5-15%, respectively, whereas the values for adults differ from the predictions made by Brandli et al. by -4% to +5%. The flow data MMEF 75-25, MEF 50 and especially MEF 25 are set at too low levels (by 5-23%) by Zapletal's and Brandli's values. Comparatively, the values predicted by Quanjer et al. for the above mentioned flow-volume parameters (with the exception of MEF 75) are too high by 4% to 12%. There are also considerable differences in respect of the reference values for IGV to the tune of +15% in the BGFA group compared to Quanjer et al.; in the BAFAM group the values differ from those of Zapletal et al. by +17%. RV yields results in the BGFA group which are higher by 11% than according to Quanjer's formulae, whereas in the BAFAM group they are higher by 15% compared to Zapletal's predictions. In respect of Rt there are differences to the predictions by Ruhle and Matthys by +16% (BGFA group) and +13% (BAFAM group), respectively. The BAFAM group differs from Zapletal's predictions by +11%. Looking at the reference limit values the overall impression is confirmed that the predictions after Quanjer et al. and mostly also those by Zapletal are too low in respect of the abovementioned lung function parameters (in the majority of cases not 5% of the examined probands, as expected, are below those levels, but only about 2%). Females, who had been underrepresented in the previous healthy proband groups, show larger deviations than males in respect of most of the parameters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7792285 TI - [Pulmonary manifestations of systemic scleroderma: pathophysiologic and clinical significance of the activation of lung fibroblasts]. AB - Fibrosing alveolitis (FA) is a common and often fatal complication of systemic sclerosis (SSC). The purpose of this study was to characterize the fibrotic process within the lungs using bronchoalveolar lavage fluid (BALF). We investigated 25 healthy controls (CON) and 85 SSC patients. In 61 patients (72%) lung function tests, clinical, and radiological findings indicated manifest FA, whereas 24 patients (28%) where free of significant lung disease. Of the latter, 12 had pathologic BAL differential cell counts (= subclinical alveolitis; SUB), 12 had normal BAL cytology (NOR). BAL samples were analysed for chemoattractant activity (CAA) for fibroblasts using Boyden chambers. Procollagen-III-Peptide (P III-P) and Laminin fragment P1 (Lam-P1) were measured radioimmunologically. CAA (expressed as % of the effect of conditioned medium) was increased in FA and SUB (CON: 17.3 +/- 3.2; FA: 40.8 +/- 5.8, p < 0.01 vs. CON; SUB: 58.6 +/- 11.8, p < 0.01 vs. CON; NOR: 23.7 +/- 6.3; n.s.). Lam-P1 [U/ml ELF] was also elevated in FA and SUB patients (CON: 0.90 +/- 0.17; FA: 2.07 +/- 0.48, p < 0.05 vs. CON; SUB: 2.61 +/- 1.14, p < 0.05 vs. CON; NOR: 1.05 +/- 0.35, n.s. vs. CON). P-III-P [U/ml ELF] was elevated in FA patients (CON: 8.3 +/- 1.1; FA: 26.9 +/- 5.5, p < 0.001 vs. CON) but not in SUB or NOR (SUB: 10.2 +/- 0.7, NOR: 7.9 +/- 2.9; n.s.). There was no significant relationship between P-III-P and LAM-P1 values in ELF and serum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792286 TI - [Lung function in chronic persistent pulmonary embolism]. AB - Chronic thromboembolic pulmonary hypertension is characterized by widespread obstruction of the pulmonary arteries with organized thrombus. Typically, the afflicted patients present with complaints of progressive dyspnea and exercise intolerance. The typical functional picture of the 22 patients in this series revealed normal lung volumes. Only about 10% of the subjects had mild restrictive defects. The universal findings were mild to moderate hypoxemia, chronic respiratory alkalosis, high pulmonary vascular resistance and low cardiac output. Pathophysiological mechanisms responsible for dyspnea in chronic thromboembolic pulmonary hypertension are discussed. PMID- 7792287 TI - [Primary amyloidosis of the lung]. AB - We report on a female patient of 66 years of age in whom primary nodular amyloidosis of the lung was diagnosed on the basis of a chance radiological finding. Based on this case report we discuss the pathophysiology, diagnosis and clinical findings of pulmonary amyloidosis. PMID- 7792288 TI - Are traditional prognostic criteria useful in pancreatic abscess? AB - Pancreatic abscess remains a potentially lethal disease. Efforts to relate outcome to the severity of associated pancreatitis or the type of surgical drainage employed have yielded conflicting results. This study was designed to test the validity of traditional prognostic criteria in the clinical setting of pancreatic abscess and to determine whether the technique of surgical drainage employed correlated with survival. The records of 40 consecutive patients with pancreatic abscess were reviewed. In each case the diagnosis was confirmed by operation. Prognostic factors analyzed included number of Ranson criteria, etiology, type, and number of microorganisms isolated, extent of abscess, time to diagnosis and operation, and technique of surgical drainage. Of the 11 Ranson criteria evaluated, only an elevation in blood urea nitrogen > 5 mg/dl correlated with decreased survival (p < 0.001). Polymicrobial abscesses (three or more organisms) resulted in a higher mortality than abscesses where fewer than three organisms were isolated (45.4 vs 13.8%; p < 0.05). Intraperitoneal extension of the abscess was associated with an increased mortality rate compared to those confined to the retroperitoneum (57.1 vs 15.2%; p < 0.01). In patients requiring unplanned reexploration, mortality was significantly increased (42.9 vs 11.5%; p < 0.05). The technique of surgical drainage employed (open versus closed) did not influence overall mortality (23.5 vs 21.7%; p = NS). Extent of disease at operation, polymicrobial abscess, reexploration for persistent or recurrent disease, and deterioration in renal function were all predictive of increased mortality in cases of pancreatic abscess.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792289 TI - The course of pain is the same in alcohol- and nonalcohol-induced chronic pancreatitis. AB - The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 +/- 8.0 years (median, 9.0 years). By the end of our follow up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis. PMID- 7792290 TI - Cyst fluid NB/70K concentration and leukocyte esterase: two new markers for differentiating pancreatic serous tumors from pseudocysts. AB - Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished. PMID- 7792291 TI - Detection of beta cell-specific DNA damage in streptozotocin-treated rats by in situ nick translation with immunostaining of alpha cells. AB - In situ nick translation with immunostaining of alpha cells could demonstrate the specific localization of streptozotocin- (STZ) induced DNA damage in beta cells using in vivo materials. The extent of DNA damage was determined through autoradiography by counting the number of grains in the nucleus of the alpha, beta, and exocrine cells of the rat pancreas. Subsequently, in situ nick translation with immunostaining of alpha cells was carried out in a pancreas pretreated with STZ. The number of grains observed in the beta cells of the STZ treated groups was significantly higher than that in the control group. DNA damage of pancreatic beta cells due to STZ could be detected visually using in situ nick translation with immunostaining of alpha cells. Moreover, it was also possible to compare the DNA damage in the individual cells of the pancreas. PMID- 7792292 TI - Supramaximal secretagogue stimulation enhances heat shock protein expression in the rat pancreas. AB - Heat shock or stress proteins (HSPs) are synthesized by various cell types in response to different metabolic insults (e.g., hyperthermia). Although the function of HSPs is not fully understood, they are believed to be an evolutionary conserved intracellular defense mechanism. In an attempt to characterize the autoprotective potential of pancreatic acinar cells, we investigated the regulation of HSPs of the 70-kD family and the small HSP ubiquitin in vitro and in vivo during supramaximal cerulein stimulation. Infusion of the secretagogue cerulein induces a mild edematous form of pancreatitis in vivo and is characterized by a marked disturbance of the intracellular transport and segregation of enzymes. Synthesis of HSP70 mRNA is upregulated in isolated pancreatic lobules by either cerulein (100 nM) or hyperthermia (42 degrees C for 60 min). In contrast, expression of ubiquitin mRNA was not altered by either secretagogue treatment or hyperthermia. This heat shock-like response of pancreatic acinar cells could be reproduced in vivo: Pancreatitis was induced in male Wistar rats by intravenous infusion of supramaximal doses of cerulein (10 micrograms/kg/h). Analysis of mRNA expression revealed a significant upregulation of HSP70 RNA during supramaximal secretagogue stimulation. mRNA levels encoding for ubiquitin remained unchanged. Western blot analysis demonstrated that the transcriptional upregulation of HSP70 in vivo was reflected on the protein level. This study demonstrates that the marked intracellular disturbance observed in secretagogue-induced pancreatitis is associated with enhanced expression and synthesis of a major stress protein. Given the autoprotective potential of HSPs, this upregulation may indicate a self-defense mechanism of pancreatic acinar cells in experimental pancreatitis. PMID- 7792293 TI - Comparison of two dose-response techniques to study the pancreatic secretory response to intraduodenal tryptophan in the absence and presence of the M1 receptor antagonist telenzepine. AB - To answer the questions if the type of continuous dose-response technique influences the pancreatic secretory response to intraduodenal tryptophan and if the M1-receptor antagonist telenzepine influences the intestinal absorption of tryptophan, we determined, in 12 conscious dogs with chronic gastric and duodenal fistulas, pancreatic bicarbonate and protein secretion and tryptophan plasma concentrations following intraduodenal tryptophan perfusion using two dose response techniques. With an ascending continuous dose-response technique (aDRT), tryptophan was perfused in loads ranging from 0.12 to 10.0 mmol h-1, starting with the lowest load and tripling it every 45 min. With the descending continuous dose-response technique (dDRT), the order of tryptophan loads was reversed, with the highest load being given first. All studies were done on a fixed background of intravenous secretin (20.5 pmol kg-1 h-1) and repeated in the presence of the anticholinergic M1-receptor antagonist telenzepine (243 nmol kg-1 h-1). The bicarbonate and protein response as well as tryptophan plasma concentrations to the same loads of tryptophan did not differ significantly between the two techniques. Using both techniques, telenzepine significantly (p < 0.05) inhibited the overall pancreatic protein response by 65% (dDRT) to 81% (aDRT). The overall bicarbonate response was only numerically, and not statistically significantly, inhibited by telezepine. Tryptophan plasma concentrations after duodenal perfusion with tryptophan were neither influenced by the order of tryptophan loads nor altered by telenzepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792294 TI - Evidence of heterotrimeric G-protein involvement in regulated exocytosis from permeabilized pancreatic acini. AB - Constitutive membrane trafficking events are regulated by heterotrimeric G proteins (G-proteins) in addition to their regulation by small GTP-binding proteins (smgs). Here, we used streptolysin O-permeabilized mouse pancreatic acini and compounds that interact with G-proteins, but not smgs, to examine whether G-proteins are also involved in regulated pancreatic exocytosis. The wasp venom mastoparan (10 microM) inhibited by 25-50% amylase release from permeabilized acini stimulated by various combinations of Ca2+, cyclic AMP (cAMP), 12-O-tetradecanoylphorbol 13-acetate, and guanosine (5'-[gamma thio]triphosphate (GTP gamma S), while the inactive analogue Mas17 was without effect. Pretreatment of intact acini with pertussis toxin resulted in an approximately 30% reduction of amylase secretion from cells subsequently permeabilized and stimulated with calcium and GTP gamma S. Pretreatment of intact acini with cholera toxin increased stimulated amylase release by 30% from subsequently permeabilized cells, and this effect was mimicked by 8-Br-cAMP. The cAMP-dependent protein kinase inhibitor H-89 (3 microM) largely reversed the effect of cholera toxin, indicating that cholera toxin's effect is due to increased cellular cAMP levels. The inhibitory effects of mastoparan and pertussis toxin suggest that a Gi/Go-type G-protein(s) is (are) involved in the regulation of exocytosis. Since mastoparan inhibited exocytosis stimulated by all intracellular mediators tested, it indicates that the G-protein acts at a distal step in the exocytic process. PMID- 7792296 TI - Evidence for the role of pancreatic acinar cells in the production of ornithine and guanidinoacetic acid by L-arginine:glycine amidinotransferase. AB - L-Arginine:glycine amidinotransferase (transamidinase) occurs at high concentrations in the kidney and the pancreas of rats. The cellular localization of transamidinase was investigated in fetal, neonatal, and adult rat pancreatic tissue using three indicators of the presence of transamidinase: (1) immunofluorescence microscopy, (2) in vitro enzymatic activity measurements on homogenates of whole pancreas and on isolated acinar and islet tissue from adult rats, and (3) ornithine production from perfused adult rat pancreas. The cellular localization of transamidinase was determined in fetal, neonatal, and adult rat pancreas, using a polyclonal guinea pig antibody made against a highly purified preparation of kidney transamidinase. Immunoreactive transamidinase was detected only in the pancreatic acinar cells. The cellular distribution of the immunostaining was compatible with the presence of transamidinase in mitochondria. The transamidinase enzymatic activity of whole pancreatic homogenates was 13.4 +/- 0.7 U/g wet weight (n = 11). In pancreata where islets had been isolated away from the acinar tissue, the transamidinase activity was similar to that of the whole pancreatic homogenates (16.8 +/- 2 U/g wet weight). Any transamidinase activity present in isolated islets was below the sensitivity of the assay. Transamidinase activity in the isolated perfused pancreas was determined by measuring the amount of ornithine released into the perfusate. The transamidinase activity of the perfused pancreas was 16.4 +/- 1.8 U/g pancreas and is an estimate of the physiological production capacity of the enzyme (270 +/ 29 nmol ornithine/min/g pancreas). These results indicate that transamidinase is present at high concentrations in the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792297 TI - Somatostatin inhibits cholecystokinin-induced pancreatic protein secretion via cholinergic pathways. AB - Although somatostatin is a potent inhibitor of pancreatic exocrine secretion in vivo, its mechanism of action remains unclear. The influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion was studied in conscious dogs. Chronic pancreatic fistulae were created in six mongrel dogs, and a second group of six dogs also underwent complete pancreatic denervation. The pancreatic responses to graded doses of cholecystokinin (12.5-200 ng/kg/h) and bethanechol (57-916 micrograms/kg/h), both alone and during background infusion of somatostatin-14 (800 pm/kg/h), were determined in all dogs. The cholecystokinin dose-response with a somatostatin-14 background was then repeated with the addition of atropine (10 micrograms/kg/h). In both groups of animals, cholecystokinin elicited a dose-dependent increase in pancreatic protein secretion that was inhibited significantly by somatostatin-14. Regardless of the status of extrapancreatic nerves, atropine further inhibited cholecystokinin induced protein secretion beyond that evoked by somatostatin-14. In both innervated and denervated animals, cholinergic stimulation with bethanechol elicited a dose-dependent increase in pancreatic protein secretion that was unaffected by somatostatin-14. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Somatostatin-14 appears to inhibit cholecystokinin-induced pancreatic secretion by an intrapancreatic cholinergic mechanism. PMID- 7792295 TI - Dynamics of pancreatic tyrosine kinase and phospholipase D activities in the course of cerulein-induced acute pancreatitis and during regeneration. AB - Acute pancreatitis can be induced in the rat by high doses of cerulein, a cholecystokinin analogue. Regeneration of the pancreatic gland after this aggression can be accelerated by endogenous or exogenous cholecystokinin. However, the biochemical and molecular events associated with the cholecystokinin induced regeneration process have not yet been identified. This study was therefore undertaken to determine the potential involvement of particulate and crude cytosolic tyrosine kinases as well as phospholipase D (PLD) in the course of pancreatitis induction and during regeneration. Acute pancreatitis was induced by cerulein, 12 micrograms kg-1, every 8 h for 2 days; this treatment was followed by 3 days of rest, and the regeneration treatment was started on the morning of the sixth day, with cerulein given at 1 microgram kg-1 every 8 h for 1 4 days. Animals were sacrificed 1, 3, 6, 12, 24, and 48 h after the first cerulein injection (high dose), on the morning of the sixth day (end of the rest period), and on the morning of the seventh and tenth days (low dose, regeneration period). After sacrifice, pancreata were excised and prepared for tyrosine kinase and PLD assays. Parallel increases in tyrosine kinase and PLD activities were observed from 6 to 48 h during pancreatitis induction and at the end of the resting period. Activities returned to control values during the regeneration period in the untreated cerulein-pancreatitis groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792298 TI - Pancreatic exocrine secretion in response to median raphe stimulation in anesthetized rats. AB - To investigate a possible role of the central serotonergic system in the central control of pancreatic exocrine secretion, the median raphe nucleus of the anesthetized rat was electrically stimulated. The parameters of the biphasic square wave stimulus were 2 V, 2 ms, and 40 Hz. Electrical stimulation of the median raphe nucleus for 10 min resulted in large increases in pancreatic volume flow and protein output. The pancreatic responses were completely abolished by spinal cord transection at the level between C4 and C5. Cervical vagotomy or adrenalectomy failed to attenuate the pancreatic responses. The median raphe stimulation evoked a remarkable elevation of the blood pressure of the carotid artery as well as the plasma concentrations of noradrenaline and adrenaline. The responses were also completely inhibited by spinal cord transection but unaffected by cervical vagotomy. Adrenalectomy blocked the elevation of the plasma concentration of adrenaline only. Noradrenaline, given intravenously, stimulated the pancreatic volume flow and protein output. The actions of noradrenaline were antagonized by propranolol but not by phentolamine. It is, therefore, concluded from the present study that the median raphe nucleus may play a stimulatory role in pancreatic exocrine secretion of anesthetized rats and that the stimulatory role is mediated via the sympathetic nervous system acting on beta-adrenoceptors. PMID- 7792299 TI - Painless acute pancreatitis mimicking pancreatic carcinoma. AB - Painful acute pancreatitis masking pancreatic carcinoma and painless acute pancreatitis with shock or coma as leading symptoms have been described before. We report a first case of almost-painless pancreatitis mimicking pancreatic carcinoma with spontaneous normalization of symptoms and biochemical as well as imaging procedure findings. PMID- 7792300 TI - Very late recurrence of a somatostatin cell tumor of the head of the pancreas. PMID- 7792301 TI - Chronic sclerosing pancreatitis in Sjogren's syndrome: a case report. PMID- 7792303 TI - Pharmacokinetic drug interactions. Part 2: Drugs D-O. PMID- 7792304 TI - Chitosan microspheres of diclofenac sodium, II: In vitro and in vivo evaluation. AB - A biodegradable diclofenac sodium (DS) microsphere system using chitosan has been characterized and evaluated in vitro and in vivo. The particle size distribution and drug content was determined. The release rate data were investigated by using zero-order, first-order, Hixson-Crowel and Higuchi kinetics. The optimum DS Chitosan microsphere formulation, empty chitosan microspheres, sustained release commercial product and plain drug were evaluated for pharmacological activity. The ulcerogenic index in rabbits was also determined. PMID- 7792305 TI - Abietane diterpenes from Lepechinia urbaniana. AB - Lepechinia urbaniana was investigated with respect to abietane diterpenes. In addition to four widespread diterpenes, two rare compounds were isolated and characterized. PMID- 7792306 TI - [One hundred years of biotechnology in the chemical industry in the example of E. Merck, Darmstadt]. AB - The purposeful use of microorganisms as producers of pure substances began about one hundred years ago with the production of lactic acid, followed by citric acid and by sorbose for the synthesis of vitamin C. The growth of pure cultures of microorganisms in a technical scale became available nearly fifty years ago by the development of the fermenter. By this it became possible to produce penicillin and other antibiotics, to transform substances in steroid syntheses and to get many enzymes, alkaloids, and other substances from microorganisms. The development of some of the older processes as basis of actual use of biotechnology at E. Merck is described, followed by some facts of the early situation in Germany and some remarks on the inclusions of biotechnology within the chemical industry. PMID- 7792302 TI - Response to Kloppel and Maillet. PMID- 7792307 TI - Synthesis of 1-[2-(4-phenylpiperazinyl-1)ethyl]imidazolidine derivatives and their pharmacological activity. PMID- 7792308 TI - Determination of heavy metals in samples of plant drugs by differential pulse polarography. PMID- 7792309 TI - Antiestrogenic properties of raloxifene. AB - This 21-day, open-label study evaluated the effects of raloxifene and tamoxifen on estrogen-induced changes in serum levels of anterior pituitary hormones (prolactin, luteinizing hormone, and follicle-stimulating hormone), sex steroids (testosterone, estradiol), and binding globulins [thyroid binding globulin (T3 resin uptake), transcortin, sex steroid binding globulin]. Seventeen healthy male volunteers completed the study after being randomized to one of three treatments: raloxifene, tamoxifen, or placebo. Six subjects received raloxifene (200 mg daily) for 10 days, 6 subjects received tamoxifen [20 mg twice a day (b.i.d.)] for 10 days, and 5 subjects received placebo for 10 days. All subjects received ethinyl estradiol (20 micrograms b.i.d.) for 7 days starting 3 days after initiation of study drug or placebo treatment. Results of the primary analysis of this study indicate that for six of the seven analyzable parameters of estrogen action (excluding luteinizing hormone) raloxifene blunted the estrogen response; this effect was significant only for T3 resin uptake. Tamoxifen administration significantly blunted or reversed the estrogen effect in all six of these parameters. Raloxifene, an effective antiestrogen in animal models, is also antiestrogenic in humans. PMID- 7792310 TI - Quantitative analysis of the electrocorticogram after forebrain ischemia in the rat. AB - The purpose of the study was to test the hypothesis that the postischemic neuronal damage is accompanied by changes of the electrocorticogram (ECoG) of freely moving rats during long-term recovery after forebrain ischemia. Ten minutes forebrain ischemia was induced in male Wistar rats. ECoG was recorded 1 day before as well as 1 h, 1 day and 7 days after ischemia. The ECoG power was calculated and for characterizing postischemic ECoG development the percentage of preischemic ECoG power was evaluated. The awake state of the rats was considered for analysis only. Furthermore, the neuroprotective effect of phencyclidine (PCP, 5 mg/kg i.v., 15 min prior to ischemia) was demonstrated in the ECoG changes. One hour after ischemia the ECoG power of the theta (4.75-6.75 Hz), alpha (7.00-12.50 Hz) and beta (12.75-18.50 Hz) band was decreased compared with sham-operated controls and PCP did not influence these changes. However, 1 day after ischemia ECoG power of the saline-treated ischemic rats was completely restored and no longer different from that of the sham-operated group. PCP-treated ischemic animals showed significantly elevated ECoG power in comparison with saline treated animals. Seven days after ischemia ECoG power of the saline-treated ischemic rats again decreased. In comparison with the ischemic controls, the ECoG activity of the PCP-treated ischemic rats was significantly higher. PCP maintained postischemic ECoG power at the non-ischemic control level. It is suggested that the decrease in the ECoG activity several days after ischemia is related to the delayed neuronal damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792311 TI - Age-related changes in vascular reactivity in genetically diabetic rats. AB - A long-term study to identify age-dependent alterations in vascular reactivity in obese Zucker rats, a model for non-insulin-dependent diabetes mellitus, was carried out. On aortic rings of 12-week-old obese Zucker rats, but not in older animals (36 and 52 weeks), the following different effects in comparison to the lean rat control group were observed: (i) a significantly enhanced maximal relaxation to acetylcholine and A23187, which was abolished by the nitric oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME); relaxation of aortic rings to the endothelium-independent vasodilator nitroglycerin was similar; (ii) more pronounced maximal 5-hydroxytryptamine-induced-contractions in the presence of L-NAME, and (iii) a more pronounced reduction in phenylephrine-induced contractions by verapamil. These results are suggestive of an altered calcium metabolism in the first weeks of development in the obese rat strain, which is probably responsible for the hypotension seen in this early time period. PMID- 7792313 TI - Different pharmacological actions of adenosine on gastric function and mucosal damage in normotensive and spontaneously hypertensive rats. AB - It has been reported that there are functional defects in the purinergic system in spontaneously hypertensive rats (SHR). The following experiments examined the gastric effects of adenosine in these animals. SHR had a significantly higher gastric mucosal blood flow (GMBF), but the secretion of acid and pepsin was not different from that of normotensive counterparts. In SHR, adenosine (s.c. 3.75 or 7.5 mg/kg) time- and dose-dependently decreased gastric acid secretion and GMBF. The nucleoside, however, did not affect the pepsin secretion. In normotensive rats, gastric acid secretion was also reduced, but not to the extent of SHR. The GMBF was increased instead. Adenosine potentiated ethanol-induced mucosal damage in SHR, which was likely caused by GMBF reduction. It is concluded that adenosine produces a greater depressive action on the stomach in SHR. These differential actions are probably due to the genetic difference between the two types of animals. PMID- 7792312 TI - Activation of protein kinase C inhibits potassium currents in cultured endothelial cells. AB - The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13 dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration. PMID- 7792314 TI - Effect of zinc on the anti-inflammatory and ulcerogenic activities of indometacin and diclofenac. AB - In the present study, the potential anti-inflammatory activity of zinc sulfate (zinc) has been examined in rats with acute and chronic inflammation. Additionally, we studied the effect of the concurrent administration of zinc on the anti-inflammatory activity of indometacin and diclofenac and their gastric side effects. Oral or subcutaneous administration of zinc (25 and 15 mg/kg, respectively) significantly reduced carrageenan-induced paw edema. Subcutaneous co-administration of zinc (15 mg/kg) and indometacin (5 mg/kg) or diclofenac (10 mg/kg) resulted in a further reduction in paw edema which was more than either that produced by either agent alone. However, after oral co-administration of zinc and diclofenac the reduction in paw edema was not significantly different from that produced by either zinc or diclofenac alone. In rats with chronic inflammation, the administration of zinc (5 mg/kg s.c. for 7 days) proved as effective as either indometacin (3 mg/kg) or diclofenac (5 mg/kg). Co administration of zinc with indometacin or diclofenac did not affect the level of activity of either drug. Co-administration of zinc did not affect the ulcerogenic effect of indometacin expressed as the ulcer index. In contrast to indometacin, administration of zinc markedly reduced the ulcerative action of diclofenac. In conclusion, zinc supplementation may contribute significantly to the treatment of inflammation. The combination of zinc with other anti-inflammatory drugs may provide beneficial additive effects and reduce their gastric hazards, particularly with diclofenac. PMID- 7792315 TI - Tissue angiotensin generation and regulation of vascular tone. AB - The renin-angiotensin system is intimately involved in the control of sodium and water balance, the activity of the sympathetic nervous system, mitogenesis and the regulation of vascular tone. There is evidence that many of these effects may be controlled at a local level by independent tissue renin-angiotensin systems. Drugs that are specific inhibitors of the cascade have proved powerful tools for dissecting the physiology of the renin-angiotensin system, and are of major benefit in the treatment of hypertension and chronic heart failure. Recent evidence suggests that variations in the genes coding for components of the system may affect the risk of developing hypertension and ischaemic heart disease. PMID- 7792316 TI - Control of vascular resistance in the maternal and feto-placental arterial beds. AB - This review aims to provide a comprehensive summary of the mechanisms involved in the physiological adaptation of the vasculature to pregnancy. Profound changes occur both systemically and in discrete circulations in the mother, but it is debatable which factors are responsible. Similarly, whilst the feto-placental circulation must be substantially controlled by humoral mechanisms, the exact role of each potential contributor is not known. In view of the hitherto unappreciated and very important role of the endothelium-derived vasodilator, nitric oxide, in the control of peripheral vascular resistance, considerable emphasis will be placed on the many recent investigations in this area. PMID- 7792317 TI - The circadian system and the therapeutics of the affective disorders. AB - Establishing that a circadian rhythm is abnormal tells us little about the cause, which can arise from changes in the patient's lifestyle, irregularities of the body clock or a malfunction in the process of entrainment of the clock. In a clinical context, such a range of possible explanations implies differences in the most appropriate mode of treatment. Against this background, the conventional view that the underlying abnormality in endogenous depression is due to a disorder of the body clock is challenged. The challenge is based on difficulties of interpretation of the clinical data and the results of studies on circadian rhythms in patients. It is suggested that the state of the circadian system in depression resembles its state in healthy individuals after time-zone transitions or in shift work maladaptation syndrome and that this disturbance should be seen as resulting from changes in the phasing of external zeitgebers rather than from an abnormality in the clock itself. PMID- 7792318 TI - Interferons alpha, beta and gamma therapy of anogenital human papillomavirus infections. AB - Anogenital condyloma acuminatum (genital warts) is the most commonly diagnosed sexually transmitted viral disease in the United States. At least 14 of the more than 60 types of human papillomaviruses (HPVs) are responsible for condyloma acuminatum. Anogenital condyloma acuminatum has a broad spectrum of manifestations in men and women, including subclinical latent infection, clinically apparent warts, abnormal genital cytology and squamous carcinoma. Traditional therapeutic modalities include cytolytic chemical agents and ablative techniques. These anti-wart methods are used in an attempt to eliminate clinically apparent disease. However, they are associated with high rates of recurrence because they do not eradicate the subclinical or latent reservoir of HPV remaining in adjacent epithelial cells and mucous membranes. Immunologic therapy with interferons (IFNs) represents a promising new antiviral modality that can be directed against all sites of infection, including clinical, subclinical and latent disease. IFN-alpha, IFN-beta and IFN-gamma are the three major groups of IFNs. These three groups of IFNs have been used successfully as monotherapy or in combination with traditional modalities to treat anogenital condyloma acuminatum. This review focuses on IFN-alpha, IFN-beta and IFN-gamma therapy of anogenital HPV infections. PMID- 7792319 TI - Families and schizophrenia redux. PMID- 7792320 TI - Linguistic reference performance in parents of schizophrenic patients. AB - Clinicians have often reported observing subtle signs of thought disorder or communication difficulties in parents of schizophrenic patients. Ascertaining empirically whether these impressions are valid and, if so, clarifying the nature of such disturbances is important for at least two reasons. First, it could assist in elucidating the etiologies of the illness. If distinguishing parental characteristics could be clearly defined, then further research could be undertaken to determine to what extent they represent genetic vulnerability markers, pathogenic environmental influences, or behavioral responses to having a disordered offspring. Secondly, it could facilitate our understanding of the cognitive processes involved in schizophrenia or in the constitutional vulnerability to schizophrenia. PMID- 7792321 TI - Fusion in the parent relationship of schizophrenics. AB - Parents of schizophrenics have increasingly been included in the treatment of their offspring, either in psychoeducational oriented approaches (Anderson et al. 1980) or in regular family therapy (Hoffman 1981). However, the success of such interventions may depend on the nature of the parental relationship. Furthermore, in designing treatment programs for schizophrenics that include their parents, the particularities of the parental relationship need to be taken into account. Hence, descriptions of the relationship between parents of schizophrenics should be valuable for the clinician. Providing such descriptions is the general aim of the present study. PMID- 7792322 TI - Beyond the biopsychosocial model: integrating disorder, health, and recovery. PMID- 7792323 TI - DSM-III-R Axis IV: clinician reliability and comparability to patients' reports of stressor severity. AB - Stress has long been considered an important precipitant to the development or exacerbation of psychopathology (Selye 1980). However, it has been difficult to reach agreement on how to measure stressors reliably, and whether stressors should be assessed using an objective clinical rating or a subjective appraisal (Mazure and Druss 1995). When the DSM-III multiaxial diagnostic system was derived, Axis IV was designed to provide a mechanism for objectively rating the severity of psychosocial stressors that contributed to the development or exacerbation of psychiatric disorders (Williams 1985). With the continued use of this nosological system, DSM-III-R Axis IV has become the most commonly used assessment of stressors in clinical settings today. The current work focuses on whether DSM-III-R Axis IV can be used reliably by clinicians generating objective ratings, and on whether these objective ratings reflect patients' appraisals of the severity of their psychosocial stressors. Based on this work, options for future use of Axis IV are discussed. PMID- 7792324 TI - Longitudinal analysis of communication deviance in the families of schizophrenic patients. AB - Considerable research on the family's contribution to the psychopathology and coping of mentally ill offspring has focused on disturbed parental communication patterns, in which parents are unable to share a common focus of attention and meaning with their children. This style of communication has been referred to as communication deviance (CD - Wynne and Singer 1963). Specifically, CD refers to instances in which speakers leave ideas incomplete, use language in an odd manner, use unclear referents, contradict previously made statements with little explanation, or make unintelligible or tangential statements. PMID- 7792325 TI - Nonverbal perceptual organization output disability and schizophrenia spectrum symptomatology. AB - Patients with neurodevelopmental syndromes often receive numerous psychiatric diagnoses before the true nature of their disorder becomes apparent. We present a case in which the neuropsychological evaluation played a significant role in reconceptualizing a patient who had received, at various times, diagnoses of schizotypal personality disorder, schizoaffective disorder, and schizophrenia. The identification of specific cognitive deficits in executive functioning, perceptual organization, visual-spatial problem solving, and abstraction led to: 1) a diagnosis of nonverbal perceptual-organization-output disabled; 2) the adoption of a rehabilitative treatment model; and 3) a greater understanding of the way in which the patient's social deficits represented adaptations to her cognitive impairments. Research data and theoretical models relating cognitive deficits to psychiatric symptoms are discussed, and evidence is presented that schizophrenia and certain neurodevelopmental syndromes may share commonalities of pathophysiology. Diagnostic issues arising from similarities between these disorders are discussed. It is suggested that direct comparisons between these groups can aid in clarifying the specific nature of cognitive deficit-symptom relationships, as well as leading to improvements in the understanding, diagnosis and treatment of schizophrenic and neurodevelopmental syndromes. PMID- 7792326 TI - Implications of mind-body theory for integration in psychiatry. AB - Recently, several authors have called for an integration of philosophy, psychology, and neuroscience regarding the mind-brain problem (Brothers 1989; Cooper 1985; Hundert 1989). In this essay I review two philosophical theories of mind that lead to very different conclusions regarding integration. Reductionist materialism is the theory that currently has the widest acceptance. Unity theory, a less familiar theory, may present the most plausible alternative to reductionism currently available. Numerous examples from the psychiatric literature are used to illustrate the challenge that faces each of these theories. Critical evaluation of how they meet the challenge, particularly in accounting for apparent psychosomatic causation, shows the strengths and weaknesses of each theory, particularly regarding their clinical utility in psychiatry. PMID- 7792327 TI - Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome. AB - Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [18F]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency. PMID- 7792328 TI - Serum cortisol levels are related to moods of elation and dysphoria in new mothers. AB - Serum cortisol levels were measured in 163 women on the third day after childbirth. Significantly elevated levels of cortisol were found to be associated with the "blues," and significantly lower levels characterized women who exhibited mild hypomania (the "highs"). Low levels of cortisol were independently associated with epidural anesthesia, while elevated levels were related to assisted delivery. There was no significant association with breast or bottle feeding. Changes in serum cortisol were thus found to parallel the mild bidirectional changes in affect that frequently follow childbirth. PMID- 7792329 TI - A prospective follow-along study of the course of social phobia. AB - The goals of this study were to delineate the courses of social phobia and to determine whether the course of generalized and specific social phobia differed. In the Harvard/Brown Longitudinal Study of Anxiety Research Project, 66 specific and 74 generalized social phobic subjects were identified for whom adequate course data were available. These subjects had been followed prospectively with a standardized follow-along measure of psychopathology. The probability of remission was calculated for each individual group and both groups combined. Demographics were the same for both groups except that the specific social phobia group had a marginally higher mean score on the Global Assessment Scale. Complete remission for the combined group was not different from that for either subgroup and was 0.11 at 65 weeks. Social phobia appears to be a disorder with considerable long-term morbidity. Surprisingly, both subtypes took a comparably long time to remit and were similar in their high level of psychosocial dysfunction. PMID- 7792330 TI - Attentional abilities and measures of schizotypy: their variation and covariation in schizophrenic patients, their siblings, and normal control subjects. AB - Thirty-five schizophrenic patients in the early stages of illness, 26 of their healthy siblings, and 35 normal control subjects performed the Continuous Performance Test, Identical Pairs version (CPT-IP). Both schizophrenic patients and their siblings were significantly impaired in their attentional performance compared with normal subjects. These results support impaired attention as a vulnerability marker of schizophrenia and indicate that at-risk siblings of schizophrenic patients display attentional deficits comparable to those found for the offspring of schizophrenic parents. By contrast, a decline in performance with the onset of a distraction condition (auditory and visual stimuli) was seen only in schizophrenic patients; siblings and normal control subjects did not differ from one another in response to experimental distraction. Therefore, it was concluded that differential distractibility is likely to be a state marker of schizophrenia. In clinical assessments, healthy siblings rated themselves as experiencing significantly more physical anhedonia than did normal control subjects, but the siblings did not differ from normal control subjects in self rated perceptual aberrations. Contrary to expectation, performance on the CPT-IP did not correlate significantly with either anhedonia or perceptual aberration in high-risk siblings. These results suggest that psychometrically measured "psychosis proneness" and neuropsychologically detected deficits may tap two nonoverlapping sources of vulnerability to schizophrenia. PMID- 7792331 TI - Relapse criteria in schizophrenic disorders: different perspectives. AB - Relapse and exacerbation of psychotic symptoms were investigated in a prospective study of 88 patients with recent-onset schizophrenia and related disorders. Relapse definitions were derived from expressed emotion and family intervention studies and based on the Brief Psychiatric Rating Scale (BPRS), the Present State Examination, and clinical judgment. Results indicate that research and clinical criteria represent different perspectives on relapse. Clinical criteria provide a validity check that can verify BPRS-rated changes in partially remitted patients. PMID- 7792332 TI - Geniculocalcarine hyperintensities on brain magnetic resonance imaging associated with visual hallucinations in the elderly. AB - Magnetic resonance scans of five geriatric patients presenting with formed visual hallucinations in the absence of other psychopathology were compared with those of 12 healthy elderly subjects for the presence and extent of subcortical and periventricular signal hyperintensity. While the number of discrete brain lesions did not differ between groups, scans from the patient group contained a higher incidence (100% vs. 50%) and greater mean size (11.1 vs. 2.9 mm) of periventricular signal hyperintensity in the posterior region. Peripheral visual acuity was impaired in all of the patients, but cerebrovascular risk factors were not elevated in this group. The authors suggest that structural abnormalities in the area of the primary visual pathway may predispose some older individuals, particularly those with poor peripheral visual acuity, to develop the symptom of visual hallucination. PMID- 7792333 TI - Ipsilateral subcortical atrophy associated with temporal lobectomy. AB - Stereologic methods for determining the volume of cerebral structures in vivo via magnetic resonance imaging have identified unilateral hippocampal atrophy among patients with complex partial epilepsy of temporal lobe origin. Metabolic imaging has also identified altered metabolism in temporal as well as extratemporal regions among these patients. As the temporal cortex and subcortical nuclei of the limbic system are reciprocally connected with striatal projection fields, we examined the putamen nuclei for evidence of associated extratemporal volume asymmetry in patients before and after temporal lobectomy. There was no evidence of preoperative putamen volume asymmetry, but a significant postoperative decrement in ipsilateral putamen volume was observed. The magnitude of postsurgical putamen volume asymmetry was correlated with the duration of time since resection. Progressive degeneration of extratemporal projections of the temporal lobe may occur in association with temporal lobectomy. PMID- 7792334 TI - Comparing means based on generalized matched sampling. PMID- 7792335 TI - Trial of interferon in chronic alcoholism. PMID- 7792336 TI - DSM-III-R Axis I and II disorders in agoraphobic inpatients with and without panic disorder before and after psychosocial treatment. AB - Panic disorder patients with agoraphobia (n = 32) and agoraphobic patients without panic disorder (n = 18) who were participants in an inpatient behavioral psychodynamic treatment program were assessed repeatedly from pretreatment to 2 year posttreatment follow-up. At pretreatment, there were statistical trends for more of the panic with agoraphobia patients to have obsessive-compulsive disorder and alcohol abuse/dependence, and for more of the agoraphobia without panic patients to have generalized anxiety disorder and avoidant personality disorder. There was also a trend for more of the panic with agoraphobia patients to have met criteria for major depression during the 2-year follow-up period. PMID- 7792337 TI - Seasonal affective disorder in a tropical country: a case report. AB - Seasonality and affective disorders in the Southern Hemisphere were investigated in populations living in latitudes (40 degrees S) equivalent to those of the studies conducted in the Northern Hemisphere. The authors describe a patient with bipolar II affective disorder who was living in a low-latitude area (Sao Paulo, latitude: 23 degrees 39' S). The patient experienced five episodes of affective disorder that began in the summer and were characterized by symptoms typical of an autumn-winter depression. During the last two depressive episodes, the symptoms remitted after a 4-week course of evening light therapy. The case calls attention to the possibility that seasonality may influence the natural history of affective disorders even in lower latitude regions. PMID- 7792338 TI - Does recruitment method make a difference? Effects on protocol retention and treatment outcome in elderly depressed patients. AB - The specific aim of this study was to contrast effects of recruitment method (solicited, referred) on demographic, psychosocial, medical, and treatment outcome measures in an ongoing clinical trial of maintenance therapies in late life depression. Data from 125 elderly patients (56 solicited via media campaign, 69 clinically referred) with recurrent, unipolar major depression were available for analysis. Several statistical contrast procedures, including group t tests, chi 2 tests, survival analysis, and logistic regression, were used to assess differences in patient profiles related to method of recruitment. Referred patients included a higher proportion of African Americans and had a lower level of education, fewer economic resources, and higher chronic medical burden. Solicited patients had been in the index episode longer than the referred patients at the time of protocol entry and were 3.4 times more likely to have experienced a "provoking agent" (severe life event or chronic difficulty) during the 6 months that preceded the onset of depressive symptoms. In contrast to these demographic and illness history differences, there were no differences in treatment response rates or time to response related to recruitment method. Solicited patients had an overall treatment response rate of 71% versus 62% in the referred group. Median time to response was 14.3 weeks in the solicited group and 13.6 weeks in the referred group. These results suggest that the inclusion of solicited patients in geriatric depression clinical trials does not bias short term treatment outcome. PMID- 7792339 TI - Platelet monoamine oxidase activity and deficit syndrome schizophrenia. AB - Measures of affective flattening that combine self-reported emotional experience with observed affect may identify deficit syndrome patients better than ratings based on observed affect alone. In this study, we examined 23 clinically stable but chronically ill schizophrenic patients, 15 of whom were found to have a deficit syndrome. After exclusion of patients with self-reported depressed mood from the deficit syndrome group, the remaining patients with a deficit syndrome not accompanied by self-reported depressed mood showed a strikingly homogeneous distribution of platelet monoamine oxidase activity. Results suggest that inclusion of self-reported emotional experience in clinical definitions of the deficit syndrome will increase the specificity of diagnosis. PMID- 7792341 TI - Wisconsin card sorting test and work performance in schizophrenia. AB - Patients with schizophrenia have long been observed to perform poorly on the Wisconsin Card Sorting Test (WCST). Although numerous studies have established links between WCST performance and specific and diffuse structural brain abnormalities, little is known about its relationship to occupational functioning. The present study has investigated the relationship between behavior at a vocational work placement and performance on the WCST test for 89 subjects with schizophrenia or schizoaffective disorder. Multiple regression analyses that examined select WCST raw scores and that covaried out IQ and Digit Symbol Subtest scores found that Task Orientation at work was significantly related to WCST Trials to the First Category and Total Number Correct. Multiple regression analyses that examined standard scores, corrected for age and education, revealed that Task Orientation was related to Percent Conceptual Level and that Social Skills were related to Total Errors and Percent Conceptual Level. Results support the criterion-related validity of the WCST and have implications for understanding impairments in work function. PMID- 7792340 TI - Borna disease virus and schizophrenia. AB - The development of a new serological assay method to detect antibodies in human sera recognizing Borna disease virus (BDV) proteins and a clinical pilot study are presented. Psychiatric patients from a schizophrenia research clinic in Baltimore, Maryland, were examined for antibodies to BDV antigen with traditional indirect immunofluorescence assays (IFA) that used both single and double labeling techniques and also with a Western blot assay capable of detecting antibodies to the three BDV proteins from a human neuroblastoma cell line. Thirteen of 90 (14.4%) patients and 0/20 control subjects had antibodies that recognized more than one BDV protein on the Western blot. Three patients had antibodies that recognized all three BDV proteins. Magnetic resonance imaging assessments of the volume of the putamen (with controls for total cranial volume) differentiated BDV+ from BDV- patients, and there were trend differences for bilateral amygdalae and the left amygdala-hippocampal process. We conclude that: (1) the Western blot assay is superior to IFA assays in BDV serology studies, (2) detection of antibodies to more than one BDV protein is a useful working criterion for seropositivity, (3) the 14.5 kDa BDV protein is 10 times more predictive of seropositivity than either the 38/40 kDa or the 24 kDa protein, (4) there is tentative evidence for a schizophrenia-control difference in the prevalence of anti-BDV antibodies, and (5) it is likely that there are neuroanatomical/behavioral features that differentiate seropositive from seronegative schizophrenic patients. PMID- 7792342 TI - Diurnal variation in tardive dyskinesia. AB - Tardive dyskinesia (TD) is a common movement disorder that is associated with chronic neuroleptic exposure. To better characterize the clinical aspects of TD, we investigated the diurnal pattern of involuntary movements by blindly rating videotaped examinations of patients from the morning shortly after awakening and later in the same afternoon. In 10 patients, average TD ratings were worse in the afternoon than in the morning, especially in the case of limb-trunk dyskinesias. These findings suggest that it is important to rate patients at the same time of day in TD studies. Moreover, patients should be evaluated at least several hours after awakening. PMID- 7792343 TI - Abnormal processing of irrelevant information in attention deficit hyperactivity disorder. AB - The presence of a selective attention deficit in children with attention deficit hyperactivity disorder (ADHD) was investigated by administering a trial-by-trial version of the Stroop Color-Naming Task to children, aged 9-12, with ADHD (n = 19) and age-matched normal control children (n = 19). Performance was evaluated on both interference and facilitation components of the task. On the standard version of the task, with equal numbers of color words and neutral words, children with ADHD showed increased Stroop interference (prolongation of color naming times by color-incongruent stimuli) but normal amounts of facilitation (speeding of color naming by color-congruent stimuli). This finding suggests that children with ADHD show increased disruption of color-naming performance by task irrelevant information, probably secondary to decreased attentional control over the interference process. In contrast to findings of studies in adults, both groups of children failed to use an attentional strategy to reduce interference when they were administered blocks of trials that varied their expectancy for color word trials. This precluded a direct test of the diminished control hypothesis. There were no significant correlations between abnormal Stroop performance and impairment on the Continuous Performance Test or the Wisconsin Card Sorting Test or measures of IQ or reading performance. The implications of these findings for our understanding of information-processing deficits in children with ADHD and of the neurobiological underpinnings of these deficits are discussed. PMID- 7792344 TI - Patterns of cognitive asymmetry and syndromes of schizotypal personality. AB - The Schizotypal Personality Questionnaire, modeled on the nine components of DSM III-R schizotypy, was administered to 122 medical students along with the Thayer Activation-Deactivation Adjective Checklist and the Warrington Recognition Memory Test for words and faces. Close affinities were found between a three-factor schizotypal personality structure and a three-syndrome model of schizophrenia. Different patterns of cognitive asymmetry (word-face discrepancy scores) were related to Active and Withdrawn syndromes as in schizophrenia, and were related to high activation and general deactivation differences as predicted. A prospective single case study showed that a face-word discrepancy before a first episode of schizophrenia accurately predicted a Withdrawn presenting syndrome. The consistency between syndromes of schizophrenia and schizotypal personality in a normal population suggests possible etiological links between the two, and it supports a dimensional view of psychosis and subclinical predispositions. PMID- 7792345 TI - Hypothalamic-pituitary-gonadal axis, prolactin, and cortisol in alcoholics during withdrawal and after three weeks of abstinence: comparison with healthy control subjects. AB - Serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone, androstenedione, estradiol, sex hormone-binding globulin, cortisol, and prolactin were measured in 12 male chronic alcoholics once during withdrawal and once after 21 days of abstinence. The results were compared with those of 14 healthy volunteers. During withdrawal, luteinizing hormone, estradiol, and cortisol levels were significantly enhanced. Estradiol and cortisol concentrations fell significantly during abstinence, whereas luteinizing hormone concentrations remained elevated. The results may be interpreted as follows: the well-known inhibitory effect of alcohol on the biosynthesis of testosterone may have led to a compensatory increase in luteinizing hormone secretion, so that normal serum concentrations of testosterone were maintained. On the other hand, peripheral conversion from androstenedione to estradiol via aromatase pathways seemed to be enhanced in chronic alcoholics, at least during withdrawal. Whether this marked increase in estradiol concentrations is implicated in different clinical and psychological symptoms seen in chronic alcoholics remains to be investigated. PMID- 7792346 TI - ICD-10 mild cognitive disorder: epidemiological evidence on its validity. AB - Criteria for the diagnosis of ICD-10 Mild Cognitive Disorder (MCD) were applied to a sample of 897 community dwelling elderly participants. Criterion A (the presence of a physical disorder) was met by 44%, Criterion B (report of a cognitive disorder) by 17%, Criterion C (an abnormality in quantified cognitive assessments) by 60%, and Criterion D (exclusion on basis of dementia and other conditions) by 74%. A total of 36 cases (4%) met all four criteria. Correlations between Criteria A and B, and B and C were weak (r = 0.18), and the correlation between Criteria A and C was almost zero (r = 0.02). This suggests that no syndrome exists. Membership of MCD was predicted by a report that memory or intelligence interfered with daily life but not by performance on cognitive tests or by a report of physical illness. Cases of MCD had higher anxiety, depression and neuroticism scores than normal elderly, but did not differ substantially on tests of cognitive functioning. These findings call into question the validity of the ICD-10 diagnosis of MCD. PMID- 7792347 TI - Can memories of childhood sexual abuse be repressed? AB - We sought studies which have attempted to test whether memories of childhood sexual abuse can be repressed. Despite our broad search criteria, which excluded only unsystematic anecdotal reports, we found only four applicable studies. We then examined these studies to assess whether the investigators: (1) presented confirmatory evidence that abuse had actually occurred; and (2) demonstrated that their subjects had actually developed amnesia for the abuse. None of the four studies provided both clear confirmation of trauma and adequate documentation of amnesia in their subjects. Thus, present clinical evidence is insufficient to permit the conclusion that individuals can repress memories of childhood sexual abuse. This finding is surprising, since many writers have implied that hundreds of thousands, or even millions of persons harbour such repressed memories. In view of the widespread recent public and scientific interest in the areas of trauma and memory, it is important to investigate further whether memories of sexual abuse can be repressed. PMID- 7792348 TI - Factors that mediate between child sexual abuse and adult psychological outcome. AB - The psychological outcome for a random community sample of women who had experienced significant childhood sexual abuse was assessed, using two outcome measures: (i) psychiatric morbidity (measured with the short PSE); (ii) self esteem. Sexual abused women with a good outcome, i.e. who were not a PSE 'case' or who had high self-esteem were compared with abused women with a poor outcome. This paper describes the post-abuse factors that modified the two outcomes. In general, a range of variables, all correlated with each other in a complex manner, distinguished good outcome subjects from poor outcome subjects. Post abuse adolescent variables included family factors (poor mother-father and parent child relationships), high school factors (poor academic, sporting and social performance) and early pregnancy. Women who had a good adolescent relationship with their father did better than expected statistically. Sport emerged as an alternative at secondary school to academic achievement in catalysing a good psychological outcome. Adult factors included the quality of relationship with partner, which was associated with a good outcome on both measures. Current paid employment was linked to high self-esteem but not to lowered psychiatric morbidity, while the converse applied for high socio-economic status. These findings imply that different processes operate for each outcome measure. A clear recognition by the school of childhood sexual abuse may help to provide the opportunity for the girl to experience success in some arena; this in turn may protect her against the likely adult consequences of low self-esteem and increased psychiatric morbidity. PMID- 7792349 TI - Ten-year follow-up of anorexia nervosa: clinical course and outcome. AB - The clinical course and outcome of anorexia nervosa are presented in a 10-year follow-up study of 76 severely ill females with anorexia nervosa who met specific diagnostic criteria and had participated in a well-documented hospital treatment study. Information was obtained on 100% of the subjects. A comprehensive assessment was made in 93% of the living subjects in specific categories of weight, eating and weight control behaviours, menstrual function, anorexic attitudes, and psychological, sexual, social and vocational adjustment. Five subjects had died, which gives a crude mortality rate of 6.6%. Standardized mortality rates demonstrated an almost 13-fold increase in mortality in the anorexia nervosa subjects. Only eighteen (23.7%) were fully recovered. Sixty-four per cent developed binge-eating at some time during their illness, 57% at least weekly. Twenty-nine (41%) were still bulimic at follow-up. The high frequency and chronicity of the bulimic symptoms plus the high rate of weight relapse (42% during the first year after hospital treatment) suggest that intensive intervention is needed to help anorexics restore and maintain their weight within a normal range and to decrease abnormal eating and weight control behaviours. PMID- 7792351 TI - Detecting psychiatric disorders in medical practice using the General Health Questionnaire. Why do cut-off scores vary? AB - In this study we assessed the accuracy of the General Health Questionnaire in detecting psychiatric disorders in general medical out-patients. A total of 290 newly referred patients were interviewed with the Present State Examination. Prior to the interview, 112 patients completed the full GHQ-60, 100 completed the GHQ-30 and 78 completed the GHQ-12. Data from the first group were used to study the full GHQ-60, together with the GHQ-30 and and GHQ-12, when disembedded from the full questionnaire. In a comparison between the disembedded and the separate versions of the GHQ-30 and GHQ-12 we observed considerable variation in the cut off scores where a certain sensitivity and specificity was attained. In ROC analysis, the versions were not materially different in their discriminatory capacity (area under the curve). The use of different criteria to define a 'case' demonstrated that case severity was another source of increasing cut-off scores. Our data demonstrate that the use of disembedded or separate versions of the questionnaire, together with variation in the case criteria can be a major explanation for variation in cut-off scores that was observed in previous studies. PMID- 7792353 TI - Attempted suicide in Oxford University students, 1976-1990. AB - During the 14 years between the beginning of academic year 1976-7 and the end of academic year 1989-90, 216 Oxford University students (119 females and 97 males) were referred to the general hospital in Oxford because of suicide attempts (254 in all). The rate of attempted suicide during university term-time (106/100,000) was lower than in other young people of similar age in Oxford City (164/100,000). The difference was particularly marked in females (178/100,000 v. 269/100,000). The lower rate in the students may in part reflect their generally higher socio economic status. Very few of the attempts by the students appeared to be failed suicides. The most frequent problems faced by the students at the time of their attempts were interpersonal, especially difficulties regarding partners, followed by academic problems. The latter were usually problems with ongoing course work rather than with the Finals examinations. Approximately a quarter of the students had psychiatric problems, with personality disorders and depression being most common. At least 30% had a history of previous attempts. Suggestions are made concerning measures for improving the management and prevention of attempted suicide by students. PMID- 7792355 TI - Obese binge eaters: metabolic characteristics, energy expenditure and dieting. AB - The study was carried out in two groups of massively obese women with BMI values who were to undergo bariatric surgery. The patients were evaluated for weight variability and for the presence and the frequency of binge eating. Body composition, resting energy expenditure (REE) and metabolic parameters were also measured. When non-bingeing individuals were compared with patients who met Binge Eating Disorder criteria, no differences in body composition, fat distribution, REE values and concentrations of serum lipids, insulin and thyroid hormones were found. On the other hand, weight variability due to reduced diet in the subjects' lifetime was significantly higher. This study does not support the hypothesis that in massively obese women binge eating is somehow induced by a reduced energy expenditure. PMID- 7792350 TI - The capacity of a measure of disability (the LSP) to predict hospital readmission in those with schizophrenia. AB - One hundred and eighteen subjects with an admission diagnosis of schizophrenia were reassessed after 12 months to establish whether hospital readmission had occurred. All subjects were rated at baseline and after 12 months on the Life Skills Profile (LSP), a 39-item measure of disability, with scores demonstrating moderate stability. The baseline LSP score was a significant predictor of readmission, both in univariate and multivariate analyses. By contrast, several univariate variables (e.g. unemployment and non-compliance with medication over the review period) did not maintain their predictive capacity in multivariate analyses, suggesting that they were manifestations or consequences of significant disability, rather than independent contributors to poor outcome. PMID- 7792352 TI - Predictors of survival with Alzheimer's disease: a community-based study. AB - Factors associated with reduced survival were investigated in elderly people diagnosed as having Alzheimer's disease (AD) and in those free of dementia at diagnosis. The study population comprised 155 people free of dementia and 222 with AD; all were aged 75 years and over and were part of a two-stage prevalence study of dementia during 1988 in Melton Mowbray, Leicestershire. An increased risk of death was found for those with a history of heavy alcohol use, lower cognitive function, a history of heart failure and those in institutional care, these factors acting in the same manner for persons free of dementia and those with AD. For the non-demented group a greater risk of death was found with increasing age and for those with a history of cancer. A greater risk of death was found for males with AD compared to females with the risk increasing over time. The longer survival of women over men may explain the sex differences found in the prevalence of AD without accompanying differences in incidence. PMID- 7792354 TI - Measuring disease severity in patients with end-stage renal disease: validity of the Craven et al. ESRD Severity Index. AB - The validity of a recently developed measure of disease severity, the End-stage Renal Disease Severity Index (Craven et al. 1991) was examined in haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients (total N = 82). Scores on the ESRD Severity Index were compared with three commonly identified components of disease severity: physiological indices of severity, functional status, and psychological burden of illness. For the entire group of subjects, scores on the ESRD Severity Index were negatively associated with functional ability and positively related to physiological severity. ESRD Severity Index scores showed a weaker relationship with psychological burden of illness which depended in part on treatment mode. Disease severity scores were positively related to depression in CAPD patients but not in HD patients. These findings suggest that the ESRD Severity Index is a valuable research tool with construct validity. PMID- 7792356 TI - Suicide among psychiatric hospital in-patients. AB - We examined for risk factors for suicide among psychiatric in-patients by comparing 37 in-patients from an Ontario Provincial Psychiatric Hospital who had committed suicide with 37 age and sex matched in-patient controls. Significantly more of the suicide victims had made a previous suicide attempt (62.2 v. 35.1%), suffered from schizophrenia (75.7 v. 35.1%), were involuntary at their last admission (70.3 v. 43.2%) and lived alone (70.3 v. 43.2%). Only six patients committed suicide on the ward. Almost a third of the patients, the majority schizophrenic, committed suicide after having been in the hospital for more than a year. These results suggest that in the psychiatric hospital setting the in patient at risk for suicide has previously exhibited suicidal behaviour, suffers from schizophrenia, was admitted involuntarily, lives alone and that the risk of suicide may remain high among long-stay schizophrenics. PMID- 7792357 TI - Isolated retrograde amnesia for autobiographical material associated with acute left temporal lobe encephalitis. AB - Retrograde amnesia for autobiographical material in the absence of anterograde amnesia or other memory disturbances was found in a patient with acute viral encephalitis. Memory loss showed a temporal gradient, but new learning was spared. Both brain perfusion imaging with 99mTc-HMPAO SPECT, and EEG localized the lesion in the left temporal lobe while CT and MRI were normal. This observation supports the anatomical differentiation between the different memory functions. The uncommon combination of isolated retrograde amnesia without other neuropsychological findings may raise the doubt of psychogenic aetiology, which in this case was refuted. PMID- 7792358 TI - Stability and change in low self-esteem: the role of psychosocial factors. AB - Low self-esteem, defined as negative evaluation of self (NES), has been shown to play a significant role in the development of depression at a case level (Brown et al. 1986). This study investigated the stability of this risk factor in 102 women over a 7-year period and examined psychosocial factors that might influence change. At the end of the 7 years about half of those originally identified as having NES no longer had it, but very few moved in the reverse direction to NES. Level of depressive symptomatology also decreased but this was not a sufficient explanation for the substantial improvement in self-esteem. Life changes that involved an improvement in the quality of close relationships or an increase in work status appeared to be the most important factors in positive NES change. Ratings made at the time of first contact of environmental difficulties and positive evaluation of self (measured independently of NES) were related to positive NES change, but only via their link with positive life changes occurring in the 7-year follow-up period. PMID- 7792359 TI - Depression undertreatment: lost cohorts, lost opportunities? PMID- 7792360 TI - Social problems as factors affecting medical consultation: a comparison between general practice attenders and community probands with emotional distress. AB - Comparison between general practice attenders and community subjects with emotional distress (as measured by GHQ-12) showed that women from a general practice sample reported more social problems than those from the community. In both men and women, problems with their spouse or partner were far more likely among general practice attenders than among community probands. Furthermore, women who consulted the general practitioners could count less often on the availability of friend confidants and had more well-defined physical disorder than their community counterparts. Results from a logistic regression analysis showed that in women (but not in men) problems in the relationship with spouse or partner increased the probability of being a general practice attender more than twofold. Physical health status did not exert a significant effect either in men or in women. PMID- 7792361 TI - Positive and negative symptoms/syndromes in schizophrenia: reliability and validity of different diagnostic systems. AB - The paper explores the reliability, concurrent validity and overlap of some positive/negative symptom rating scales and typological criteria in 100 schizophrenic patients. Rating scales include Andreasen's Scales for the Assessment of Positive and Negative Symptoms, Abrams and Taylor's Scale for Emotional Blunting, and Kay's Positive and Negative Syndrome Scale. Criteria for categorizing individual patients include Andreasen's and Kay's criteria for positive and negative types of schizophrenia as well as Carpenter's criteria for the deficit syndrome. The correlations among positive as well as among negative scales were high. The agreement among criteria tended to be lower. Both positive scales showed low internal consistency. Kay's negative scale had the greatest internal consistency, which suggests that it is measuring a homogeneous syndrome. All negative symptom scales and categorical syndromes identified a group of patients who were single and exhibited schizoid or schizotypal pre-morbid personality disorders, poor premorbid sexual/social adjustment, poor response to neuroleptics and poor prognosis. PMID- 7792362 TI - Differing patterns of electrodermal and finger pulse responsivity in schizophrenia and depression. AB - Non-response of the autonomic orienting response (OR), as indexed jointly by deficient skin conductance (SCR) and finger pulse amplitude responding (FPAR), has been shown to occur with excessive frequency in the schizophrenic population. The present study is an attempt to replicate earlier evidence that SCR-OR and FPAR-OR, when measured in concert, could distinguish schizophrenic from depressed patients (Bernstein et al. 1988). This issue is critical of the question of diagnostic specificity of OR non-responding, since reduced SCR has been found repeatedly in depression as well as in schizophrenia. We examined SCR and FPAR concurrently in 69 schizophrenic, 45 depressed, and 67 normal subjects. SCR non responding was more frequent in both schizophrenics and depressives than in normal controls, while only the schizophrenics displayed excessive FPAR non responding. Moreover, among SCR non-responders, concordant OR non-responding- defined as non-responding indexed simultaneously in both the SCR and FPAR components--was most common in the schizophrenic sample. These findings support our previous conclusion that OR non-responding in depression, may have distinct peripheral origins. Our results also suggest that measuring multiple biochemically distinct components of the OR may be more sound methodologically than obtaining a single channel recording. PMID- 7792363 TI - Autism as a strongly genetic disorder: evidence from a British twin study. AB - Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences. PMID- 7792364 TI - Loss, humiliation and entrapment among women developing depression: a patient and non-patient comparison. AB - This paper is part of a series dealing with the role of life events in the onset of depressive disorders. Women who developed depression in a general population sample in Islington in North London are contrasted with a National Health Service treated series of depressed patients in the same area. Findings among the latter confirm the importance of a severely threatening provoking event for onset among the majority of depressed women patients. The results for the two series are similar except for a small subgroup of patients characterized by a melancholic/psychotic condition with a prior episode. The severe events of importance have been recognized for some time by the traditional ratings of the Life Events and Difficulty Schedule (LEDS). However, the full descriptive material collected by the LEDS has been used to develop a new refined measure reflecting the likelihood of feelings of humiliation and being trapped following a severely threatening event, in addition to existing measures of loss or danger. The experience of humiliation and entrapment was important in provoking depression in both the patient and non-patient series. It proved to be associated with a far greater risk of depression than the experience of loss or danger without humiliation or entrapment. PMID- 7792365 TI - Time course of prefrontal lobe dysfunction in severely depressed in-patients: a longitudinal neuropsychological study. AB - The Stroop Colour-Word Test (SCWT) and the Verbal Fluency Test (VFT), two tests that have been suggested to be particularly sensitive to prefrontal dysfunction, were administered to 23 severely depressed in-patients. Both tests were impaired in patients at inclusion, but only verbal fluency normalized with successful treatment of depression. VFT impairment is consistent with the hypothesis of a left prefrontal cortex dysfunction in depression. Moreover, the persistence of an impaired performance on SCWT in patients at discharge suggests that a selective attention deficit may persist in patients beyond a clear clinical improvement. PMID- 7792366 TI - Dysfunctional attitudes in depressed and recovered depressed patients and their first-degree relatives. AB - A series of depressed probands and their first-degree relatives were categorized as follows: (a) currently depressed; (b) recovered depressed; and (c) never-ill relatives. Their scores on a subscaled version of the Dysfunctional Attitude Scale (the DAS-24) were compared. The DAS total scores mirrored previous findings in that the total scores for recovered individuals returned to normal or near normal levels. However, the dependency subscale scores remained elevated for the recovered depressed group. It is proposed that these results support the conclusion that self-report measures of cognitive vulnerability should focus on specific rather than global effects, if progress is to be made in the search for true vulnerability factors. PMID- 7792367 TI - Determinants of the help-seeking process: Goldberg and Huxley's first level and first filter. AB - This paper discusses minor psychiatric morbidity in the community and its relation to help-seeking. The research is aimed at identifying the demographic and social characteristics that enhance the likelihood of minor psychiatric morbidity, as measured by the General Health Questionnaire, and to reveal how these determinants relate to health status. In the second stage of the study, the same characteristics are related to their effect on the decision to decision to consult a general practitioner and, specifically, on presenting psycho-social problems to the GP. At the population level, the likelihood of a high GHQ score was greater for women, divorced persons and the unemployed, other variables remaining equal. However, GHQ score was contaminated by poor subjective health perception, especially for unemployed persons. Chronic physical illness did not have an independent effect on the GHQ score. Chronic physical illness did influence help-seeking. In addition, several socio-demographic characteristics showed an independent effect on consulting behaviour for both GHQ-positive and GHQ-negative patients. Women, unemployed persons and publicly insured patients with a minor psychiatric disturbance were more apt to visit their GP, regardless of their physical health status. However, no socio-demographic characteristics increased the likelihood that a GHQ-positive patient would present unambiguous psycho-social complaints as a reason to see their doctor. PMID- 7792368 TI - Abuse-related posttraumatic stress disorder: evidence for chronic neuroendocrine activation in women. AB - The following study tested the hypothesis that women with post-traumatic stress disorder (PTSD) related to childhood sexual abuse would display elevated norepinephrine-to-cortisol ratios similar to that found in male combat veterans diagnosed with PTSD. Twenty-four-hour urine samples were collected from 28 women: 11 women with PTSD who experienced childhood sexual abuse (PTSD+), 8 women who experienced childhood sexual abuse without PTSD (PTSD-), and 9 nonabused controls. All urine samples were tested for creatinine, total catecholamines, free-cortisol, and 17-ketosteroid levels. Psychological testing validated that the PTSD+ group was significantly elevated on all three subscales of the Impact of Events Scale. Both abused groups (PTSD+ and PTSD-) showed a tendency for polyuria, and the PTSD+ group showed a tendency towards obesity. Thus, neuroendocrine values (micrograms/day) were adjusted by creatinine clearance rates (creatinine mg/day/kg body weight). The corrected values indicated that the PTSD+ group had significantly elevated daily levels of norepinephrine, epinephrine, dopamine, and cortisol. However, because of the parallel elevation in cortisol, the norepinephrine-to-cortisol ratio was not significantly elevated in the PTSD+ diagnosed women in contrast to the findings reported for male PTSD patients. This discrepancy may reflect an important gender difference, an interaction between gender and age at onset of the traumatic experience (childhood abuse in females vs. combat experience in young adult males), or physiological variation related to phase of the disorder. PMID- 7792370 TI - Longitudinal follow-up of amenorrhea in eating disorders. AB - The authors recruited 229 treatment-seeking anorexic and bulimic women for a prospective, longitudinal study. Telephone interviews were arranged every 3 months for at least 1 year for 225 patients. At intake, 132 subjects were menstruating, 34 subjects were taking oral contraceptives, 5 subjects had an organic cause for amenorrhea (e.g., hysterectomy), and 58 subjects were amenorrheic. Each patient met Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) criteria for anorexia nervosa (AN, N = 41), bulimia nervosa (BN, N = 98), or AN/BN (N = 90). All subjects were interviewed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, which was modified to include a section for DSM-III-R eating disorders, the Longitudinal Interval Follow-Up Evaluation, and the Structured Interview for DSM-III Personality Disorders. It was found that body weight was associated with menstrual status: those with amenorrhea had a mean percent ideal body weight (IBW, Metropolitan Life criteria) of 74 +/- 1% compared with 102 +/- 19% for menstruating patients (p < .01). Affective illness was more prevalent among patients with amenorrhea than among menstruating patients (75% vs. 56%, p < .05). Menses were regained within 1 year by 33% of amenorrheic patients. These patients gained an average of 7.3% of their IBW. Longer duration of eating disorder (p < .03) and the presence of an anxiety disorder (p < .05) were associated with persistent amenorrhea. Menses were lost within 1 year by 8% of menstruating patients. These patients lost an average of 5.0% of their IBW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792369 TI - Blood lipids and lipoproteins in married and formerly married women. AB - As part of the Cardiovascular Occupational Risk Factors Determination in Israel (CORDIS) study, the association between marriage termination (divorce/separation or widowhood) and blood lipids and lipoproteins was examined in a sample of 351 healthy women employed in industry. Eighty-seven former spouses were each matched with three married women (N = 264) for age, number of children, smoking status, and type of job (blue/white collar). After controlling for age, number of cigarettes per day, leisure sport participation, and daily coffee consumption, former spouses in the younger women group (younger than 45 years) had significantly higher total cholesterol, total cholesterol ratio, and LDL levels than married women. Among older women (> or = 45 years), there were no significant differences. Significantly more younger former spouses had abnormally high cholesterol and LDL levels. In both age groups, former spouses smoked more cigarettes daily. These differences between the marital status groups may be explained by stress effects and changes in primary prevention practices. If replicated, such findings would delineate a population in need of intervention to reduce disease risk. PMID- 7792371 TI - Herpes simplex and mood: a prospective study. AB - The effect of mood, the common cold, amount of sleep, and sunshine on recurring herpes simplex virus (HSV) infection was investigated using daily self-reports over a 3-month period from 23 female and 15 male patients with genital herpes and 26 female and two male patients with oral herpes. Results showed recurring genital HSV infection to be preceded by reduced and decreasing overall emotional well being over a period of 10 days, with a temporary improvement in the middle of the period. This pattern was significantly represented by rated nervousness and rated alertness. Females showed more marked trends for reported mood than did the males, which could not be attributed to the menstrual cycle. Conversely, males showed a more marked, strongly significant fourth-order trend for reported amount of sleep, with nadirs on the 8th and the 3rd day before the recurrence. Neither exposure to sunshine nor the common cold showed any relation to recurrence of genital HSV infection. The common cold appeared as the major precipitating factor in oral herpes. Except for a significant fourth-order trend for rated alertness, no relationship between mood and subsequent onset was found. This negative finding was interpreted as a masking effect of the common cold. Two alternative physiological theories, the ganglion trigger theory and the skin trigger theory, were discussed in relation to present findings. It was suggested that various possible mediators between mood states and recurring herpes should be investigated using the present approach, with structured diaries as complement to the rating scales. PMID- 7792373 TI - Classical conditioning of total respiratory resistance in humans. AB - A differential classical conditioning paradigm was used to investigate changes in total respiratory resistance in healthy adult female subjects. The conditioned stimuli were red and blue colors projected on a screen, and the unconditioned stimulus was an arithmetic task in which the subject mentally subtracted serial 17s from a number displayed on the screen. One of the two colors was paired with the arithmetic problem, and the other color was presented alone. Participants completed seven paired and seven unpaired trials. Both total respiratory resistance and functional residual capacity changes were measured before and during each conditioned stimulus. Total respiratory resistance was higher during the paired conditioned stimuli than it was during the unpaired conditioned stimuli. This result was not related to variations in functional residual capacity. It was concluded that elevated total respiratory resistance during the paired stimuli was a result of conditioning. The elevations were probably due to increases in bronchomotor tone. Conditioned changes in total respiratory resistance may be related to some respiratory behaviors both in healthy individuals and in patients with asthma. PMID- 7792372 TI - Validity of the Quality of Well-Being Scale for persons with human immunodeficiency virus infection. HNRC Group. HIV Neurobehavioral Research Center. AB - To evaluate the validity of the Quality of Well-Being Scale (QWB) for studies of patients with human immunodeficiency virus (HIV) disease, 514 men were studied who were divided among four categories: Centers for Disease Control and Prevention (CDC) Group A (N = 272), CDC-B (N = 81), CDC-C (N = 47), and uninfected male controls (N = 114). The QWB and a variety of medical, neuropsychological, and biochemical measures were administered to all participants. When QWB scores were broken down by HIV group, the CDC-C group was significantly lower (.614) than the CDC-B (.679), CDC-A (.754), or control group (.801). The difference between Groups CDC-C and CDC-A was about .14 units of well being, which suggests that individuals lose 1/7 equivalents of 1 well year of life for each year they are in Group CDC-C in comparison to the asymptomatic group (Group CDC-A). In comparison to the controls, this would equal a 1-year of life loss for each seven infected individuals. The QWB was shown to be significantly associated with CD4+ lymphocytes (p < .001), clinician ratings of neuropsychological impairment (p < .04), neurologists ratings of dysfunction (p < .001), and all subscales of the Profile of Mood States. Baseline QWB scores were significant prospective predictors of death over a median follow-up time of 30 months. Multivariate models demonstrated high covariation between predictors of QWB. It was concluded that the QWB is a significant correlate of biological, neuropsychological, neurological, psychiatric, and mortality outcomes for male HIV-infected patients. PMID- 7792374 TI - Heterogeneity in neuroendocrine and immune responses to brief psychological stressors as a function of autonomic cardiac activation. AB - Human responses to brief psychological stressors are characterized by changes and large individual differences in autonomic, neuroendocrine, and immune function. The authors examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. They also used interindividual variation in heart rate reactivity, cardiac sympathetic reactivity (as indexed by preejection period reactivity in their reactivity paradigm), and cardiac vagal reactivity (as indexed by respiratory sinus arrhythmia reactivity) to explore the heterogeneity in human responses to brief psychological stressors. The results revealed that brief psychological stressors heightened cardiac activation, elevated plasma catecholamine concentrations, and affected the cellular immune response. It was also found that individuals characterized by high, relative to low, cardiac sympathetic reactivity showed higher stress-related changes in adrenocorticotropic hormone and cortisol plasma levels but comparable changes in epinephrine and norepinephrine concentrations. These data suggest that the effects of psychological stressors on cardiovascular and cellular immune response are governed by coordinated regulatory mechanism(s) and that going beyond the simple notion of heart rate reactivity to examine neural substrates may shed light on the interrelationships among and the regulatory mechanisms for the autonomic, endocrine, and immune responses to stressors. PMID- 7792376 TI - Preoperative rehearsal of active coping imagery influences subjective and hormonal responses to abdominal surgery. AB - Existing evidence suggests that preoperative psychological preparation that is designed to reduce anxiety may sensitize cortisol and adrenaline responses to surgery. In a controlled trial of abdominal surgery patients, we therefore tested the effects of a preoperative preparation that used guided imagery, not to reduce anxiety, but to increase patients' feelings of being able to cope with surgical stress; 26 imagery patients were compared with 25 controls who received, instead, background information about the hospital. State-anxiety was similar in each group, but imagery patients experienced less postoperative pain than did the controls, were less distressed by it, felt that they coped with it better, and requested less analgesia. Hormone levels measured in peripheral venous blood did not differ on the afternoon of admission, before preparation. Cortisol levels were, however, lower in imagery patients than in controls immediately before and after surgery. Noradrenaline levels were greater on these occasions in imagery patients than controls. The results are interpreted in relation to two theories. One states that preoperative "worry" reduces surgical stress. The other concerns the influence of active and passive coping on endocrine responses to stress. PMID- 7792377 TI - Affiliation moderates the effects of social threat on stress-related cardiovascular responses: boundary conditions for a laboratory model of social support. AB - The authors tested the hypothesis that the response-attenuating effects of affiliation under stress are limited to conditions that involve high social threat. Ninety-six young adult women were exposed to standardized psychological challenges in one of four conditions that involved two levels of social affiliation (alone or accompanied by a close friend) and two levels of social threat (variations in the social behavior and perceived status of the experimenter). Social affiliation was associated with attenuated blood pressure responses to the challenges but only under conditions of high social threat. Affiliation was not associated with differences in self-reported emotional response to the challenges nor with alterations in cognitive task appraisal. Exploratory analyses suggested that some of these effects were stronger in hostile or socially avoidant individuals. Implications of these findings for interpreting the literature on social support and cardiovascular reactivity, and for understanding the potential role of social support in reducing stress-related disease pathogenesis, are discussed. PMID- 7792375 TI - Acute psychological stress and epinephrine infusion in normolipidemic and hyperlipidemic men: effects on plasma lipid and apoprotein concentrations. AB - This study examined whether psychological stress and the infusion of epinephrine increase plasma lipid and apoprotein concentrations in normolipidemic and hyperlipidemic men. Subjects were studied during three separate 6-hour laboratory sessions: a control session, during which subjects rested quietly while blood samples and hemodynamic measurements were obtained; a stress session, during which subjects were presented with two challenging mental tasks, followed by quiet rest; and an epinephrine infusion session, during which subjects received a low-dose infusion of epinephrine followed by quiet rest. The stress and epinephrine infusion manipulations produced the expected changes in plasma epinephrine and norepinephrine levels, blood pressure, and heart rate. Free fatty acid concentration increased markedly during epinephrine infusion and less dramatically but consistently during mental stress. Both stress and epinephrine infusion produced acute increases in plasma total, low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol and apoprotein B concentrations, but comparable increases during the control session were not observed. Changes in albumin concentration (an index of plasma volume) were associated with changes in lipid concentrations during psychological stress. Epinephrine increases during psychological stress were correlated with increases in free fatty acid and triglyceride levels both during and after task administration. It was concluded that psychological or pharmacological stress induced in the laboratory produces changes in lipid concentrations, which at least during psychological stress, may be attributed to concomitant changes in plasma volume. The association between task-induced changes in epinephrine and changes in free fatty acid and triglyceride levels, also supports the hypothesis that psychological stress increases lipolysis. PMID- 7792378 TI - Clinical speculation: is specificity back? This time thromboangiitis obliterans. AB - Do men with thrombangiitis obliterans (TO) show conspicuous personality features and behavior? Twenty-one men with TO were compared with 20 men with coronary artery disease (CAD). All diagnoses were angiographically confirmed. Mean ages were 40.1 (TO) and 43.4 years (CAD). Semistructured, open-ended interviews were conducted. Interview-behavior: TOs were more hostile, minimizing, evasive, and complicated than CADs (p < .001). The interviewer reacted with more anger, impatience, boredom, astonishment, and less empathy towards TOs (p < .001). Adult behavior: TOs had changed their place of work more often (p < .001), had more absentism from work (p < .001), and had more debts (p = .01) unrelated to the present illness. They smoked more before the illness (p = .01) and continued to smoke more frequently during their illness than CADs (p < .003). They were more often single or divorced (p < .05) and had more conflicts in their relationships (p < .001) than CADs. During conflicts, TOs more often shouted or withdrew and less frequently tried to resolve conflicts with humor and discussions (p < .001) than CADs. TOs were more frequently dissatisfied with their life situation than CADs (p < .001). TOs more often passively submitted to their illness than CADs, who tried to cope by giving up smoking and by exercising (p < .001). Childhood: TOs more often mentioned a bad relationship with their father than CADS (p = .01) and had more disciplinary problems at home and in school (p = .002). TOs show remarkable personality features.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792379 TI - Psychosis in an adolescent patient with Wilson's disease: effects of chelation therapy. AB - Wilson's disease is a rare genetic disorder involving the liver and brain, with onset frequently in adolescence. Psychiatric symptoms are often the first manifestation of the disease and can obscure the diagnosis. Chelation therapy can reverse the fatal outcome of untreated patients, so early detection is critically important. This paper describes an adolescent with Wilson's disease who, after initiation of penicillamine therapy, developed florid psychosis that improved as copper levels were decreased and that did not require use of neuroleptic medication. PMID- 7792380 TI - Aerobic exercise and the placebo effect: a controlled study. PMID- 7792382 TI - [Behavioral markers of premature infants--a study of "temperament in early childhood"]. AB - In a two-point longitudinal study we compared preterm and fullterm infants with respect to certain behaviour patterns known as "infant temperament". Interdependencies between depression and childrearing attitudes of the mothers and temperamental characteristics of infants are analysed. Investigations took place after birth and four months (corrected age) later and comprised, among other questionnaires, a new German temperament assessment scale as well as clinical data. Our results show that, independent of their depression and childrearing attitudes, mothers of preterm infants describe their babies as showing much less positive emotions and having far more problems in being soothed. In both groups the baby's positive reactions and soothability was related to the extent of its mother's motivation to stimulate the baby and care for it. However, showing many negative emotions cannot sufficiently be explained by prematurity and certain mother characteristics at time of birth. PMID- 7792383 TI - [Patients in (post)modern society--does psychosomatic medicine still have concrete foundations?]. AB - The paper describes the scientific development psychosomatic medicine has undergone in the last decades, as well as the politically induced changes in the German Health Care system. In three future scenarios the dangers of a) biological and b) voluntaristic schools of thought are presented along with the c) consequences of ecological destruction and economic power. The increasing trend for psychosomatic medicine to use salutogenetic models is discussed as a feasible approach for the prevention of fear-provoking perspectives. PMID- 7792381 TI - Effects of sleep on the production of cytokines in humans. AB - The restorative functions of sleep may affect immunologic functioning. The present study examined the effects of sleep on stimulated cytokine release in 13 healthy men. The subjects spent 2 experimental nights in the sleep laboratory. In one condition, lights were turned off at 11:00 PM to enable sleep for 3.5 hours. Thereafter, they stayed awake till 7:00 AM. In the other condition, conversely, subjects stayed awake between 11:00 PM and 3:00 AM. Then, lights were turned off for a 3.5-hour phase of sleep. Blood was sampled every 30 minutes between 11:00 PM and 7:00 AM. Sleep was monitored by polysomnographic recordings. Release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was determined after stimulation of mononuclear cells with lipopolysaccharide from Escherichia coli. The release of IL-2 was stimulated with phytohemagglutinin. Compared with wakefulness, after 3 hours of sleep, production of TNF-alpha and IL 1 beta was substantially diminished (p < .01). Production of IL-2 was enhanced during sleep (p < .05), with this effect being limited to the second nocturnal sleep phase after 3:00 AM. Sleep-dependent changes in stimulated cytokine release were independent of changes in plasma cortisol concentrations. These results indicate a specific reducing effect of sleep (vs. wakefulness) on cytokine production by monocytes (TNF-alpha and IL-1 beta). The rather slow development of the effects calls for further studies to establish the exact time course of the influence of sleep on cytokine production. PMID- 7792384 TI - [Which factors modify the duration of inpatient psychotherapy?]. AB - The indication for differential duration of inpatient psychotherapy is a difficult question to answer, especially when the possible outcome-success of more severely disturbed patients (e.g. with borderline-personality disorder) is considered. Our own results showed no relevant correlation between the degree of patients' disturbance and treatment duration, neither any relevant correlation between treatment duration and therapists' evaluation of symptomatic or ego structural improvement. The only marked effect on treatment duration was found for the patients' evaluation of their therapeutic relationship: the better they judged this relationship, the more their therapists tended to elongate inpatient psychotherapy. This finding supports a paradigm, which has been already well confirmed for outpatient psychotherapy: the specific importance of the therapeutic relationship for the therapeutic process even within the scope of inpatient psychotherapy. Another finding of our study indicates that more severely disturbed patients probably need a modified setting of inpatient psychotherapy: favorably a focus oriented interval treatment with short duration periods and alternating focus if necessary. PMID- 7792385 TI - [Alexithymic verbal behavior in patients with Crohn disease]. AB - This study investigates the language of Morbus Crohn patients using a quantitative, objective linguistic method which was developed by M. v. Rad (1983). Significant results were: The language of Morbus Crohn patients is more generalized and includes not only fewer emotional terms but also fewer differential emotional terms than the language of neurotic patients. This result supports the hypotheses that the language of Morbus Crohn patients is alexithyme and that the Morbus Crohn disease belongs to psychosomatic disorders. PMID- 7792386 TI - [Clinical and psychometric findings in spasmodic torticollis]. AB - In a previous study screening for psychopathological symptoms in a sample of 256 patients with spasmodic torticollis had resulted in 27% of patients, whose mean score of the GSI of the SCL-90-R was above the double standard deviation of the control group of normals (Scheidt et al. 1994). In this study the self-reported psychopathology of a subsample of 19 TS patients was controlled for its agreement with a clinical assessment in a psychiatric interview. The results of the study confirm the validity of the SCL-90-R as a screening instrument for psychological distress and psychopathology. However a tendency for social desirability in a subgroup of patients might lead to underestimate the degree of psychological distress in this patient group and might als account for some of the discrepant findings concerning psychological distress and psychopathology in TS in former studies. Furthermore the clinical assessment revealed a high psychiatric and psychosomatic morbidity prior to the onset of the spasmodic torticollis as well as a high frequency of traumatic life events (e.g. bereavement) in the patients premorbid history. In addition to coping with a crippling neurological condition concurrent psychopathology in TS therefore should be considered also in terms of the individuals premorbid psychological vulnerability. PMID- 7792388 TI - Interleukin-1 beta-stimulated PGE2 production from early first trimester human decidual cells is inhibited by dexamethasone and progesterone. AB - Cytokines are known to increase the production of prostaglandins by human decidual cells, but negative regulators have not been identified. We have examined the effects of dexamethasone and progesterone on prostaglandin (PG) E2 synthesis by cultured human first trimester decidual cells. The numbers of cyclooxygenase (COX) enzyme positive cells were visualised by immunocytochemistry, using antibodies specific for COX-1 and COX-2. Interleukin-1 beta stimulated the production of prostaglandins E2 and F2 alpha dose dependently, and this was associated with increased numbers of COX-2 positive cells. Progesterone (10(-7)-10(-6) M) and dexamethasone (10(-7)-10(-6) M) inhibited basal and interleukin-1 beta-stimulated prostaglandin production, and decreased the numbers of COX-2 positive cells. Neither interleukin-1 beta nor the steroids affected numbers of COX-1 positive cells. COX-2 seems to be the main enzyme controlling the synthesis of PGE2 by human decidual cells, and may be negatively regulated by progesterone. PMID- 7792387 TI - Dose-related effect of IGF-I on placental prostanoid release. AB - Prostanoids play an important role throughout all of pregnancy and during the initiation and progress of labor. The human placenta at term produces large quantities of prostanoids, yet little is known of the factors regulating their biosynthesis. In a previous study we observed that insulin-like growth factor I (IGF-I) specifically inhibits thromboxane B2 (TxB2) and prostaglandin F2 alpha (PGF2 alpha) from human term placental explants. In these studies we have defined the dose-related action of IGF-I on the release of placental prostanoids. With use of a perifusion system, the basal release of prostaglandin E2 (PGE2), PGF2 alpha, TxB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) from human term placental explants increased from the fifth hour in culture, while the release of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) remained constant. The addition of IGF-I (5.2-83.3 ng/mL) to the perifusing medium effected an inhibition of TxB2 and PGF2 alpha. The release of TxB2 was inhibited in a dose-related fashion from the initiation of IGF-I treatment and throughout the five hours of treatment, whereas the inhibition of PGF2 alpha was significant only at a dose of 83.3 ng/mL of IGF I. Yet, the release of 6-keto-PGF1 alpha, PGE2, or PGFM was not altered by any dose of IGF-I studied. Because both TxB2 and PGF2 alpha are vasoconstrictors, we have proposed that IGF-I may enhance vasodilation in the placenta. Therefore, IGF I may allow for increased blood flow, thus affecting the maintenance of pregnancy and the supply of nutrients available for the growth of the fetus. PMID- 7792390 TI - Cervical mucus concentration of prostaglandins E2 and F2 alpha after pretreatment with mifepristone in the first trimester of pregnancy. AB - Cervical dilatation and softening after pretreatment with mifepristone are well documented. As this effect is similar to that observed after local application of prostaglandin E2 (PGE2) it is tempting to speculate that the effect of mifepristone is mediated via an increase of the endogenous secretion of prostaglandins from the cervical mucosa. Eighteen healthy women in the first trimester of pregnancy were treated with oral mifepristone (200 mg) 48 and 24 hours before legal abortion by vacuum aspiration and 18 women in the same age of gestation without any pretreatment served as controls. Cervical mucus was collected for measurement of prostaglandins by radioimmunoassay before administration of the drug and in connection with vacuum aspiration. The cervical dilatation at the time of surgery was significantly increased in women given mifepristone as compared with untreated women (7.6 versus 5.8 mm). The wet weight of collected cervical mucus was significantly increased in mifepristone treated women. The amount of PGE2 and prostaglandin F2 alpha per sample was unchanged in mifepristone-treated women, whereas the concentration was lower as an effect of dilution due to an increased yield in cervical secretion observed after mifepristone treatment. The present observation does not give any support to the hypothesis that mifepristone-induced cervical maturation is mediated via an increase in cervical prostaglandin production. PMID- 7792389 TI - Effects of a single drip infusion of lipo-prostaglandin E1 on vibratory threshold in patients with diabetic neuropathy. AB - We evaluated acute effects of prostaglandin E1 encapsulated in lipid microspheres (lipo-PGE1), in 14 type 2 diabetic patients with neuropathy. Nerve conduction velocity (NCV), vibratory threshold (VT), skin temperature and subjective symptoms were evaluated for 24 hours after a single drip infusion of lipo-PGE1. In 6 of the 14 patients, the decrease in VT (P < 0.05) more than 50% measured by an SMV-5 vibrometer was observed at 6 hours after the infusion (responders). Subjective symptoms were improved (P < 0.05) in 5 of the 6 responders, whereas it improved in only 1 of the 8 patients who had no change in VT (nonresponders). NCV did not change (P > 0.05) either in the responders or in the nonresponders by the infusion. The responders had less impairment in VT and milder retinopathy and nephropathy than the nonresponders (P < 0.05). Our results demonstrate that vibratory sensation and subjective symptoms can be improved by a single infusion of lipo-PGE1 in type 2 diabetic patients with mild neuropathy. PMID- 7792391 TI - 12-Lipoxygenase in Lewis lung carcinoma cells: molecular identity, intracellular distribution of activity and protein, and Ca(2+)-dependent translocation from cytosol to membranes. AB - Recently we demonstrated that Lewis lung (3LL) tumor cells express 12 lipoxygenase (12-LOX) mRNA and protein, respectively. In this study we partially sequenced the 12-LOX cDNA after reverse-transcription polymerase chain reaction amplification of 12-LOX mRNA from cultured 3LL cells. Comparison with platelet and leukocyte 12-LOX indicates that 3LL 12-LOX is identical with the platelet type enzyme at least within the sequenced region. Further, we investigated the intracellular distribution of both 12-LOX enzyme protein and its activity which are prerequisites for understanding 12-LOX regulation. 12-LOX activity was monitored via the production of 12-hyroxyeicosatetraenoic acid from 3LL cells and their subcellular fractions using reverse-phase high performance liquid chromatography. 12-LOX protein was measured by direct slot blot and by Western Blotting. In 3LL cells, both 12-LOX activity and 12-LOX protein were predominantly localized in the cytosol. This 12-LOX activity was optimal at 37 degrees C. However at 24 degrees C and 10 degrees C, it showed 87% and 61% of this activity, respectively, thus differing distinctly from 12-LOX in platelets or rat basophilic leukemia cells. Incubation of 3LL cell homogenates with 0-100 microM free Ca2+ and subsequent separate analyses of cytosol and membrane fractions indicated that, as in platelets, an increase in intracellular free Ca2+ caused a loss of cytosolic 12-LOX activity. However, no significant Ca(2+) induced increase in membrane-associated 12-LOX activity was observed under these conditions in 3LL cells. In contrast, at the 12-LOX protein level we observed a Ca(2+)-dependent loss in the cytosol and a concomitant increase in the membrane fraction. Thus, we suggest that 12-LOX in 3LL cells undergoes rapid translocation from cytosol to membrane in a Ca(2+)-dependent manner, but is no longer active or becomes inactivated at the membrane site. PMID- 7792392 TI - Sensitivity of ovine myometrial tissue to various eicosanoids in vitro. AB - The sensitivity of sheep myometrial tissue to prostaglandin F2 alpha (PGE2 alpha), PGE2, the thromboxane analog U-44069, and leukotrienes C4 (LTC4) and LTD4 was investigated in a superfusion system. Tissues were obtained from eight oophorectomized ewes, with or without pretreatment with estradiol-17 beta. After equilibration, spontaneous activity was abolished by adding indomethacin to the superfusion fluid. The dose needed to induce a contraction with a peak level of 50% of the median peak level of spontaneous contractions increased from PGE2 to PGF2 alpha, U-44069, LTC4, and LTD4. The differences between the doses required were significant for all compounds, except between LTC4 and LTD4. Estradiol-17 beta pretreatment caused an increase in the required dose of PGF2 alpha. The results of this study do not support the hypothesis that leukotrienes are involved in the regulation of myometrial activity. PMID- 7792393 TI - Leydig cell function and radiation: a review of the literature. PMID- 7792394 TI - Aggressive fibromatosis: optimisation of local management with a retrospective failure analysis. AB - The records of 40 consecutive patients treated at the Princess Margaret Hospital (PMH) between 1979 and 1988 for aggressive fibromatosis were reviewed. The median follow-up was 86 months (range 21-167 months). All surgery was performed at the referring hospitals. Thirty-six underwent an attempt at excision, four were biopsied. Thirty-one had no overt disease after surgery and 26 of these received adjuvant irradiation. Eight were treated with radiotherapy alone, and another was treated with azathioprine and prednisone. Twenty-four (60%) presented with recurrent disease. The overall relapse free rate was 63% at 5 and 10 years. Combined surgery and irradiation had a higher relapse rate than irradiation alone (46% vs. 25%), and a high proportion of failures in the combined group were marginal failures (36%). Relapses following surgery alone were 1/5 (20%), and chemotherapy 0/1. Tumour size greater than 8 cm predicted for relapse (p = 0.002), but tumour site, status of surgical margins, and presence or absence of a history of relapse were not statistically significant. Twelve with subsequent treatment failure underwent successful salvage surgery, and 37/40 (92%) were disease free at last follow-up. A functional assessment (modified Johnstone scale) revealed 11/24 patients (46%) with poor functional outcomes (grade 2 or less) after all treatment compared with 6/24 (25%) at referral. Ten of 11 (91%) with grade of 2 or less had a history of recurrence, and 4/5 amputations were for treatment of a painful recurrence. Treatment planning in this study was hampered by inadequate information on tumour location since few patients had clinically apparent disease when seen by the radiation oncologist (only 35% of cases) and fewer had preoperative cross-sectional imaging available (12% of cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792395 TI - Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens. AB - From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8 2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease. PMID- 7792396 TI - Radiation tolerance of normal mouse bladders after intravesical chemotherapy. AB - The aim of this study was to compare functional damage in normal mouse bladder after various initial intravesical therapies and to investigate tolerance to subsequent irradiation. Six consecutive weekly intravesical instillations of Mitomycin C (MMC) or doxorubicin (DOX) were used as the initial therapy. Irradiation with single doses of 10-25 Gy (X-rays) was given at 4 or 12 weeks after intravesical treatment. Functional bladder damage was assessed from changes in the micturition frequency, expressed as frequency index (FI, number of urination events/ml urine in a 24-h test period) and from cystometry measurements of bladder volume at 52-56 weeks. Irradiation alone caused a temporary acute response (increased FI) within the first 4 weeks and a progressive late response starting from 15 to 37 weeks, depending on the radiation dose. A reduced bladder capacity was also evident at 52-56 weeks after 25 Gy. Intravesical MMC or DOX caused a 3-fold increase in FI during intravesical therapy with recovery to control levels within 2-3 weeks after cessation of treatment. Irradiation 4 weeks after MMC, or 4 or 12 weeks after DOX resulted in acute responses very similar to irradiation alone. There was no difference in time of onset or extent of late bladder damage when irradiation was given after DOX, compared with irradiation alone as assessed from repeated measurements of FI or cystometry at 52-56 weeks. In contrast, irradiation 12 weeks after MMC led to a decrease in acute radiation response compared with X-rays alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792397 TI - Effects of continuous hyperfractionated accelerated and conventionally fractionated radiotherapy on the parotid and submandibular salivary glands of rhesus monkeys. AB - Radiotherapy is a major treatment modality for head and neck cancer. It is often not possible to exclude the salivary glands from the treatment fields. The unique susceptibility of the serous cells of the salivary glands to irradiation often results in xerostomia with ensuing secondary complications and discomfort to the patients. Recent reports have suggested that continuous hyperfractionated accelerated radiotherapy (CHART) can lead to considerably less reduction in the parotid salivary gland than conventional radiotherapy. This study was undertaken to assess histologic changes of salivary glands induced by CHART and conventional radiation fractionation schedules. The parotid and submandibular salivary glands of adult rhesus monkeys were irradiated with cobalt-60 gamma radiation at 50 Gy/20 fractions/4 weeks, 55 Gy/25 fractions/5 weeks, or 54 Gy/36 fractions/12 days (CHART). Salivary tissues were harvested at 16 weeks following irradiation and evaluated histopathologically. Microscopically, the glands receiving 50 Gy, 55 Gy, or CHART were virtually indistinguishable. There was severe atrophy and fibrosis of all glands. Quantitative analysis revealed that 50 Gy, 55 Gy, and CHART induced a reduction of serous acini in parotid glands by 86.4%, 84.8%, and 88.8%, respectively. In submandibular glands, serous acini were reduced by 99.4%, 99.0%, and 100%, respectively. The corresponding reduction in mucous acini were 98.4%, 98.4%, and 99.2%, respectively. These histopathologic and quantitative morphologic studies show that the magnitude of serous gland atrophy in the parotid and submandibular salivary glands of rhesus monkeys was similar at 16 weeks after receiving 50 Gy in 20 fractions, 55 Gy in 25 fractions, or CHART. PMID- 7792398 TI - Chemosensitization of CCNU in KHT murine tumor cells in vivo and in vitro by the agent RB 6145 and its isomer PD 144872. AB - The cytotoxicity and chemosensitizing potential of the nitrohetercyclic agent RB 6145 and its R enantiomer PD 144872 were determined in rodent tumor cells grown in tissue culture or as solid tumors. Using a clonogenic cell survival assay the degree of selective cytotoxicity of these bioreductive drugs was first determined in KHT/iv cells. Cells treated under hypoxic conditions were observed to be approximately 50-80-fold more susceptible to the action of RB 6145 or PD 144872 than were cells exposed under air. To assess the in vitro chemosensitizing potential of RB 6145 and PD 144872, doses of these agents which led to survival values between 0.5 and 1.0 under hypoxic conditions were administered, and were then combined concomitantly with variable doses of the nitrosourea CCNU. Exposure to the nitrosourea was for 1 h. The results showed that inclusion of either sensitizer enhanced the cell killing of the chemotherapeutic agent 2.4-2.6-fold. Subsequent experiments evaluated the therapeutic benefit of combining these bioreductive agents with CCNU in KHT sarcoma-bearing C3H/HeJ mice. When given at times ranging from 90 min before to 60 min after CCNU exposure, these bioreductive drugs increased the tumoricidal activity of the chemotherapeutic agent. Complete dose response curves combining RB 6145 and PD 144872 and a range of CCNU doses also were evaluated. The sensitizers (0.75 mmol/kg) were administered 30 min prior to the chemotherapeutic agent and survival of clonogenic tumor cells 22-24 h after treatment was used to assay tumor response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792399 TI - Picture archiving and communications systems in radiation oncology (PACSRO): tools for a physician-based digital image review system. AB - Digital imaging is becoming more and more important in the diagnosis, staging, and treatment of patients in radiation oncology. In order to facilitate the most efficient interface of this technology to physicians and other users of this information, a medical image display system (MID) has been developed at the Fox Chase Cancer Center (FCCC). The system runs on 20 personal computers situated in physicians offices as well as a modified system located in the radiation oncology conference room. Access to CT, MRI, and EPID information is achieved through an Ethernet connection to the hospital picture archiving and communications system (PACS). Over a 1-year period a total of 503 patients and 3845 images have been stored on the system. Physician approval using the MID system (without conventional films) was performed on 106 patients. Of these, 22%, 16%, 11%, 10%, and 9% consisted of breast, prostate, pelvic, lung, and head and neck patients, respectively. Digital images sent from a variety of image sources to the MID system take up to 15 s to process and format while image access and display can take 2-5 s, dependent upon image size and speed of the host computer. PMID- 7792400 TI - Calculation of the dose in the build-up region for high energy photon beam. Treatment planning when beam spoilers are employed. AB - Recoil electrons from a polystyrene sheet (beam spoiler) placed in a photon beam were used to modulate the dose in the build-up region. The effects of the beam spoiler on the dosimetry in simple phantoms were studied for both 6 MV and 15 MV photon beams at 100 cm source-to-surface distance (SSD) as a function of (1) the thickness of the spoiler, (2) the spoiler-to-surface distance (SD) and (3) the field size. A radiotherapy treatment planning (RTP) algorithm was used that employs pencil beam dose deposition kernels to evaluate the three-dimensional (3D) dose distribution due to photons and electrons in the build-up region. To determine the energy deposition kernels for the recoil electrons emanating from the spoiler, their energy spectrum needs to be known. Monte Carlo simulations were performed to derive the spectrum of electrons from the beam spoiler. The recoil electron spectrum was found to be nearly independent of field size, SD, and spoiler thickness. The pencil beam energy deposition kernel was calculated for the recoil electrons from the spoiler and inserted in the treatment planning algorithm. The dose calculation algorithm permits merging the photon and recoil electron dose components. In all cases the calculation agrees to within 3% of the measured results. PMID- 7792401 TI - Accuracy of field alignment in radiotherapy of head and neck cancer utilizing individualized face mask immobilization: a retrospective analysis of clinical practice. AB - Deviations between simulation and first check films were quantitatively assessed for 95 unselected head and neck cancer patients. All measured deviations- calculated on the basis of a total of 190 simulation and 380 verification films- were normally distributed, with mean values of 0-3 mm and standard deviations of 3-5 mm. Of the absolute deviations, 50% and 95% were within 3 mm and 9 mm, respectively. These results should be considered in clinical practice when prescribing safety margins and adequate cut off doses for sparing critical organs in head and neck cancer. PMID- 7792402 TI - Verification of an on line in vivo semiconductor dosimetry system for TBI with two TLD procedures. AB - This work presents the verification of an on line in vivo dosimetry system based on semiconductors. Software and hardware has been designed to convert the diode signal into absorbed dose. Final verification was made in the form of an intercomparison with two independent thermoluminiscent (TLD) dosimetry systems, under TBI conditions. PMID- 7792403 TI - Granulate of stainless steel as compensator material. AB - Compensators produced with computer controlled milling devices usually consist of a styrofoam mould, filled with an appropriate material. We investigated granulate of stainless steel as filling material. This cheap, easy to use, clean and re usable material can be obtained with an average granule diameter of 0.3 mm, enabling an accurate and reproducible filling. No wax or other sealing material is added. The density of the granulate is approximately 4.5 g/cm3, which allows an accurate production of compensators in a sufficiently wide transmission range without the compensators becoming too thick. Transmission and surface dose measurements show that the dosimetric properties of stainless steel granulate are suitable for use as compensator material. PMID- 7792404 TI - Re: SF2: clothes for the emperor? PMID- 7792405 TI - Dose escalation, treatment protraction, and the steepness of the dose-response curve for squamous cell carcinoma of the head and neck. PMID- 7792407 TI - Annual Brachytherapy Meeting. GEC-ESTRO. York, United Kingdom, 10-12 May, 1995. Abstracts. PMID- 7792406 TI - Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. AB - Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed. PMID- 7792409 TI - Analysis of an escalating sequence of problem behaviors: a case study. AB - This case study focused on a student with severe disabilities who displayed multiple problem behaviors that fit a pattern of behavioral escalation. Analysis of the pattern in which problem behaviors occurred within instructional sessions, and comparisons of conditional rates of occurrence for specific behaviors to overall base rates of occurrence, indicated that the student's problem behaviors did represent a behavioral sequence. Functional assessment led to the hypothesis that the use of rule statements by the teacher was related to the occurrence and escalation of the problem behaviors. An ABAB reversal design showed that eliminating the use of rule statements was an effective instructional intervention for decreasing the rate of the student's problem behaviors. Independent ratings of the physical effort required for specific problem behaviors in the sequence suggested that response effort may be one variable underlying the pattern of responding within a behavioral sequence. Implications are offered for our theoretical understanding of complex patterns of problem behaviors and for future research and clinical intervention. PMID- 7792408 TI - Measuring stress in the mildly intellectually handicapped: the factorial structure of the Subjective Stress Scale. AB - The Subjective Stress Scale (SSS) was developed by Bramston and Bostock (1994) to provide a sensitive measure of stress for people with intellectual disabilities. This study examined the underlying structure of the SSS by analysing responses of 221 intellectually disabled people to the questionnaire. Exploratory factor analysis of the interitem correlation matrix yielded at least three solutions that were quite interpretable: a one-factor, a two-factor, and a four-factor solution. Factors in all three solutions bore a strong resemblance to stress dimensions reported for the general population using other stress measures. The results suggest that although the actual stressors vary, persons with mild intellectual disability are affected by the same major stress dimensions as the general population. The results also suggest that the SSS can be used as a much needed measure of subjective stress levels in people with mild intellectual disabilities. PMID- 7792411 TI - Effects of task size on work-related and aberrant behaviors of youths with autism and mental retardation. AB - The effects of task size on rate of responding and on-task behavior as well as on nontask-related behaviors of students with autism and mental retardation on a repetitive task under conditions of no reinforcement for responding was analyzed. Task size, defined as the presence of either 36 or 250 beads in a container at the onset of the session, was compared in an alternating treatment design. The small-task condition resulted in higher on-task behavior for all participants and in higher work rate for four of the five participants. For the four participants who engaged in inappropriate use of task materials, higher levels of this behavior occurred in the large-task conditions. Other nontask-related behaviors were higher in the large-task condition for all participants with the exception of stereotypy, which was higher in the small-task condition for one participant. Better work-related behavior occurred for these participants in small- than in large-task conditions even though no tangible reinforcement was provided for task responding. Implications of these results are discussed in the context of arranging workplace environments to maximize productivity of persons with developmental disabilities. PMID- 7792410 TI - Suicidal behavior in children and adolescents with mental retardation. AB - Despite increasing attention to psychiatric disorders in the mentally retarded, suicidal behavior remains an underreported phenomenon in this population, particularly in children and adolescents. This study was aimed at documenting the existence of suicidal behavior among 90 consecutive admissions to a specialty unit for dually diagnosed children and adolescents in a medical school-affiliated children's psychiatric hospital. Archival chart review yielded a total of 19 patients, or 21%, for whom suicidal behavior was a presenting complaint upon admission or during hospitalization. Suicidality was distributed across gender, level of mental retardation, and psychiatric diagnosis. Additional findings of note with regard to family dysfunction and/or abuse history are summarized. Clearly, in this sample, children and adolescents with mental retardation were capable of formulating and engaging in potentially fatal acts. Results of this study suggest that suicidal behavior is an underrecognized, yet significant phenomenon in children and adolescents with mental retardation and psychiatric disorder. PMID- 7792412 TI - [Latex allergy. New risks in anesthesiologic practice]. PMID- 7792413 TI - [Hepato-pulmonary syndrome: meta-analysis]. AB - INTRODUCTION AND OBJECTIVES: The clinical introduction of multiple elimination of inert gases (MEIG) has meant a qualitative advance in our understanding of the physiopathology of a wide range of pulmonary diseases. This meta-analysis aims to bring together data on patients with cirrhosis of the liver from 3 similar studies in which MEIG was used. PATIENTS AND METHODS: The results from 30 patients in 3 studies, divided into 2 groups based on baseline partial arterial O2 pressure (hypoxemic: PaO2 < 80 mmHg, n = 17; normal: PaO2 > or = 80 mmHg, n = 13) were subjected to statistical analysis. RESULTS: The hypoxemic group experienced an increase in the percentage of cardiac output perfusing regions of shunting (10.1 +/- 10 vs. 1.08 +/- 1.6%; p < 0.01) and low ventilation/perfusion relationships (16.3 +/- 10.3 vs. 3.5 +/- 5.8%; p < 0.01). We also observed greater dispersion in the distribution of perfusion (1.09 +/- 0.43 vs. 0.67 +/- 0.34; p < 0.01) and ventilation (0.62 +/- 0.14 vs. 0.49 +/- 0.13; p < 0.05), with the ventilation mean located in regions with higher ventilation/perfusion relationships (1.3 +/- 0.5 vs. 0.85 +/- 0.15; p < 0.01). The difference between observed and calculated PaO2 was significant in the hypoxemic group (7.3 +/- 5.5 vs. 1.2 +/- 1.3 mmHg; p < 0.01). CONCLUSIONS: Hypoxemia in patients with cirrhosis of the liver is mainly due to changes in ventilation/perfusion relationships and shunting. In the most hypoxemic patients, however, we cannot rule out a role for the causes of hypoxemia, such as diffusion changes. PMID- 7792414 TI - [Intravenous anesthesia using propofol during lengthy neurosurgical interventions]. AB - OBJECTIVE: To compare the hemodynamic stability and time to recovery of consciousness after long-duration (> 3 h) neurosurgery with 2 anesthetic protocols: total intravenous anesthesia with propofol as the single hypnotic agent and inhalational anesthesia with isoflurane. PATIENTS AND METHOD: We studied 58 middle-aged patients (range 40-50 years) scheduled for intracranial surgery. The patients, who all scored over 13 on the Glasgow coma scale before surgery, were randomly divided into two groups: 27 in group I received isoflurane and 31 in group II received propofol. Anesthetic induction was with sodium thiopental 4 mg/kg i.v. in group I and with propofol 2.5 mg/kg i.v. in group II. Both groups then received fentanyl 2 micrograms/kg i.v., lidocaine 1.5 mg/kg i.v. and vecuronium 0.2 mg/kg i.v. Before placement of the Mayfield head grip, with clamps, or before start of surgery in those cases in which the head grip was not used, all patients were given a 3 micrograms/kg i.v. dose of fentanyl. Hypnosis was maintained in group I with concentrations of isoflurane that were adequate for keeping minimum alveolar concentration (MAC) between 0.6 and 1. In group II maintenance was by continuous i.v. perfusion of propofol 10 mg/kg/h for 30 min., followed by 8 mg/kg/h for 30 min. and 6 mg/kg/h until the end of surgery. N2O was never used. RESULTS: After induction systolic and mean arterial pressures (SAP and MAP) decreased significantly in both groups in comparison with baseline values (SAP: 113.1 +/- 30.0 vs. 140.9 +/- 27.08 mmHg in group I and 109.6 +/- 22.1 vs. 135.0 +/- 19.7 mmHg in group II; MAP: 76.8 +/- 18.7 vs. 95.6 +/- 17.0 mmHg in group I and 74.9 +/- 13.2 vs. 93.4 +/- 13.7 mmHg in group II). The patients in group II showed less tendency to develop arterial hypertension in response to orotracheal intubation (SAP and MAP at the moment of intubation: 156.4 +/- 33.7 and 104.6 +/- 18.1 mmHg, respectively, in group I as compared to 135.1 +/- 31.2 and 93.5 +/- 22.4 mmHg in group II; p < 0.05 between the 2 groups and p < 0.05 for the baseline and intubation pressures in group I). Time to recovery of effective, spontaneous breathing was shorter in group I (5.9 +/- 4.9 and 8.9 +/- 5.7 min.) than in group II (10.9 +/- 9.6 and 13.0 +/- 7.4 min.) and tubes could be extracted earlier from patients in the isoflurane group (10.4 +/- 6.1 min. vs. 17.6 +/- 12.8 min.; p < 0.01). We found no differences between the 2 groups for time until eye opening, response to verbal orders or time until start of spontaneous movement. CONCLUSIONS: Propofol can be considered an alternative to the traditional thiopental-isoflurane sequence in neurosurgery lasting more than 3 h. In our study the hypertensive response to the stimulus of orotracheal intubation was lower in the propofol group than in the thiopental-isoflurane group. PMID- 7792415 TI - [Latex allergy in anesthesiology]. AB - Allergy to latex, described 15 years ago, is increasing. It affects mainly certain risk groups, such as health-care workers and patients with spina bifida or genitourinary malformations. Symptoms vary in intensity from mild to life threatening and can present during any medical procedure involving skin or mucosal contact, or inhalation, of the allergen in a previously sensitized patient. The most serious cases reported have generally involved patients undergoing surgery. Prevention is based mainly on tentative diagnosis made when the patient's history is taken, followed by laboratory tests and consultation with an allergist. Because prophylactic drug protocols have proven ineffective, the patient must be offered a latex-free environment in keeping with standard recommendations. PMID- 7792416 TI - [Anesthesia in a patient with latex allergy]. AB - Anaphylactic reactions triggered by latex-based products are increasingly frequent, particularly in the hospital environment. We describe a patient with a prior history of atopic allergy and documented allergy to latex who was scheduled for abdominal surgery. A great deal of anesthetic and surgical equipment contains latex and substitutes for such material must be used in order to prevent severe hypersensitivity reactions. PMID- 7792417 TI - [Postoperative cortical blindness after resection of a retroperitoneal teratoma]. AB - We present a rare case of cerebrovascular accident involving non-cardiac, non neurological, non-carotid surgery in a 44-year-old man with no cardiovascular risk factors who underwent retroperitoneal resection of a teratocarcinoma, immediately after which he showed signs of confusion accompanied by cortical blindness. Neurological signs and symptoms remitted completely 5 days after surgery. Complementary tests and the patient's evolution confirmed a diagnosis of reversible ischemic neurological deficit. PMID- 7792419 TI - [Anesthetic management of the achondroplastic patient]. PMID- 7792418 TI - [Anesthetic implications in antiphospholipid syndrome. 2 clinical cases]. AB - Anti-phospholipid syndrome, originally called anticardiolipin syndrome, is characterized by the presence of anti-phospholipid antibodies and a marked tendency to both arterial and venous thrombosis. The little information available on the implications of this syndrome for anesthesia derive from the recent description of the disease. We describe 2 patients, each with 1 of the 2 forms of antiphospholipid syndrome that have been described to date, and each needing surgery for a different reason. The first was a 24-year-old woman who was admitted to the hospital with diarrhea, fever and metrorrhagia in her fifth month of pregnancy. Blood tests revealed a weakly positive title of anti-cardiolipin antibodies. Steroid and antiplatelet therapy was begun. Delivery was at 35 weeks by elective cesarean with epidural anesthesia due to oligoamnios. The second patient was 52-year-old woman with a history of 13 miscarriages, cerebrovascular accident and deep venous thrombosis. She had been diagnosed as having systemic lupus erythematosus with anti-phospholipid syndrome and was receiving corticoid and antiplatelet therapy. She had been admitted on 2 occasions for epistaxis, purpura in the lower extremities and severe thrombocytopenia. The last condition did not respond well to immunosuppressant therapy and a splenectomy was therefore performed with the patient under general anesthesia. In both cases recovery was good in spite of the serious complications of anesthetic management. PMID- 7792420 TI - [Anesthesia device compatibile with magnetic resonance]. PMID- 7792421 TI - [2 cases of anesthesia in long-QT syndrome]. PMID- 7792423 TI - [Heart transplantation as an alternative to conventional surgical revascularization in extensive coronary disease with severe ventricular dysfunction. Arguments against it]. PMID- 7792422 TI - [Cardiac herniation after bilobectomy with partial pericardectomy]. PMID- 7792424 TI - [Heart transplantation as an alternative to conventional surgical revascularization in extensive coronary disease with severe ventricular dysfunction. Arguments in its favor]. PMID- 7792425 TI - [Quality of life in patients with pacemakers]. AB - INTRODUCTION AND OBJECTIVES: On the occasion of the doctoral thesis "Epidemiologic study in pacemaker patients", the social and some health factors around the pacemaker patient has been studied. METHODS: Data were obtained by a patient verbal questionnaire and the pacemaker follow-up form. The social parameters studied are: employment aspects, change life feeling, health feeling, sporting activity and change of intensity of pharmacologic treatment. Just to get alone a quantitative social parameter, a social resulting punctuation or "social balance" has been designed. It has been used in bi-variable relation against the symptoms, electrocardiogram, complications, time from the pacemaker implantation, pacemaker type, dependence of the pacemaker and social variables between himself. Among the 108 variables considered, it has been studied which of them had more weight in the "pacemaker profitability". Greatest profitability (and vice versa): greatest profit in symptoms and in social conditions, smallest number of complications; greater time passed and worst evolution of electrocardiogram. The numerical value of the "profitability" is set up by assigning 20 points to each foregoing concepts, obtaining a greatest theoretical punctuation of 100 points and a smallest of 0 points. RESULTS: We obtained values of arithmetical mean, a frequency profile of quality life parameters, a profile of the better and worst situation in the bi-variable relation and the definition of those social factors who contributed to the segmentation of the "pacemaker profitability". CONCLUSIONS: The kind of job and the time of going out of it after the pacemaker implantation, the changing life feeling, the health feeling after the pacemaker and the transport means to the hospital are the variables which contributed to discriminate the major and the minor profitability. PMID- 7792426 TI - [Univentricular heart with left morphology with permeable atrio-ventricular valves. Study of the bulbo-ventricular foramen with color echo-Doppler. Importance for the surgical repair]. AB - INTRODUCTION AND OBJECTIVES: Bidimensional and color-coded Doppler echocardiography were used to study 19 patients with univentricular heart, permeable atrioventricular valves, muscular bulbo-ventricular foramen and an anterior rudimentary chamber. We evaluated the influence of the foramen upon the size of the great vessels, and in consequence the most appropriated surgical techniques. MATERIAL AND METHODS: The foramen was measured in two projections at the end of the systolic period, and its area was calculated, according to the body surface, with the formula S = pi (D1/2 x D2/2). Indexes lower than 2 cm2/m2 were considered as restrictive. We studied 19 patients that presented a mean age of 11 +/- 12 years (range 1 day-39 years). The patients were classified in two groups. Group A: patients who had transposition of the great vessels (13 cases). Group B: patients who had normal connection of the great vessels (6 cases). Each group was classified in two subgroups: subgroup 1, patients who presented a restrictive foramen, and subgroup 2, patients who presented a normal foramen. In this study, we evaluated the associated cardiac anomalies. RESULTS: Group A. Thirteen cases. The index value for the whole group was 2.47 +/- 1.18 cm2/m2. The first subgroup included 6 cases with a restrictive foramen, 2 patients presented pathology of the arch. Four patients had a pressure gradient between the ventricle and the rudimentary chamber beyond 20 mmHg. The index of this subgroup was 1.68 +/- 0.39 cm2/m2, the median was 1.7. Seven cases, with a normal foramen, were included in the second subgroup, six of them had pulmonary valve stenosis, and the other one had undergone a pulmonary artery bandage 2 months before. Only one patient had a gradient pressure at the foramen beyond 20 mmHg. The index for this second subgroup was 3.34 +/- 0.83 cm2/m2. GROUP B: Six patients with normal connection of the great vessels were included. The index was 1.56 +/- 1.17 cm2/m2. The first subgroup included 3 cases with a restrictive foramen. The index was 0.72 +/- 0.29 cm2/m2 (range 0.41-1) and the median was 0.75. Pressure gradient between the ventricle and the rudimentary chamber was greater than 20 mmHg. Three patients with a normal foramen were in the second subgroup and here, the index was under normal limits 2.4 +/- 0.52 cm2/m2 (range 2.1-3), the median was 2.1. One patient underwent a pulmonary artery bandage two months before. CONCLUSIONS: Bulbo-ventricular foramen size/body surface index may exert an influence on the size of the vessel connected to the rudimentary chamber. The index vary in a negative way with the evolution time, or in those cases with transposition of the great vessels after a pulmonary artery bandage. Whenever the foramen is restrictive, the pulmonary artery or the aorta have a smaller diameter and the pressure gradient between the ventricle and the rudimentary chamber rises. PMID- 7792427 TI - [Non-surgical extraction of intravascular foreign bodies in children. Experience with 8 cases]. AB - BACKGROUND AND OBJECTIVES: Foreign body retrieval in the catheter room is a useful procedure at any age, but, although its interest, few reports of such technique have been reported in children. METHODS: We review and present our experience in 8 children, aged 5 days to 11 years, five of them having congenital hearts defects. RESULTS: We retrieved 4 catheter fragments, 2 endocardial electrode catheter tips, 1 Rashkind 12 mm. PDA umbrella, and 1 detachable Jackson coil. All of them were placed in systemic veins, right heart chambers or pulmonary arteries. We used biplane fluoroscopy and percutaneous right femoral vein puncture in all cases. Goose-Neck (Microvena Corporation) snares were used in 5 patients, hand made snares in 2 and a Swan-Ganz catheter in one. In 4 cases, the snare was introduced trough a Mullins long sheath and the foreign body pulled into its distal end, in order to bring it out of the femoral vein. Six foreign bodies came off the femoral vein: 4 trough the puncture site and 2 needing a venous cut-down. The two remaining foreign bodies, stopped while pulling at the common iliac vein and a minor surgical procedure was needed for final extraction. CONCLUSIONS: Therapeutic catheterization is the technique of choice for intravascular foreign body retrieval in children. PMID- 7792428 TI - [Anatomic correction of transposition of great vessels with entire interventricular septum. Initial results]. AB - INTRODUCTION: Optimal management for patients with simple transposition of great arteries is currently the arterial switch operation. We review our initial experience to evaluate the results. METHOD: From 1988 to 1993, 21 children with simple transposition of the great arteries underwent arterial switch operation. Mean age at surgery was 10.5 +/- 5.6 days, excluding two cases with two-stage arterial switch and one with late diagnosis. Patent ductus arteriosus was present in 12 cases, and a small ventricular septal defect in two. The coronary artery pattern was unusual in 9 cases. Balloon atrial septostomy was performed in 19 cases, seven of them using two-dimensional echocardiography. It was considered no necessary in the remaining two, with a large ductus arteriosus. RESULTS: Total circulatory arrest was used in 13 patients (mean time 29.7 +/- 22.6 min). Three patients died in the early postoperative period (14.3%) in a refractory cardiac failure, one of them secondary to myocardial necrosis. The coronary artery pattern was unusual in two of died patients. All patients but three were in sinus rythm. Mean age at follow-up was 21 months (follow-up range 2 months to 5 years). Seventeen of surviving patients are in a functional state grade I and one in grade II of NYHA. There haven't been late deaths. CONCLUSION: These results compared with the ones of atrial switch operation, have encouraged to us to use the arterial switch operation in all children with simple transposition of the great arteries. Increasing experience will likely lead to improve our results. PMID- 7792429 TI - [Cardiovascular pharmacology (XII). Pharmacologic interventions in the progression of coronary atherosclerosis]. PMID- 7792430 TI - [Anomalous origin of the circumflex artery from the pulmonary artery in a patient with rheumatic mitral stenosis]. AB - Left circumflex coronary artery arising from the pulmonary artery is an infrequent congenital anomaly, only described once in an adult patient. We present one patient with rheumatic mitral stenosis in whom this anomaly was noticed when an angiography was performed prior to a percutaneous mitral valvuloplasty. PMID- 7792431 TI - [Orthotopic heart transplantation in a patient with previously undiagnosed persistence of the left superior vena cava]. AB - The amount of transplants has gone through a remarkable increase during the last years. As a result, congenital anomalies of little prevalence appear more and more often while performing the transplants. The persistence of upper cava vein is one of them and, if not linked to other anomalies, it usually remains unnoticed. This article presents a case of an orthotopic cardiac transplant in a patient with an upper cava vein duplication not diagnosed before undergoing surgery, and it compares the way it was handled to diverse techniques previously described. PMID- 7792432 TI - [Left aorto-ventricular tunnel. Diagnosis with transthoracic and transesophageal echo-Doppler]. AB - Aortic-left ventricular tunnel is an infrequent congenital heart lesion consisting of an abnormal tubular-shaped communication between the aortic root and the left ventricle that bypasses the aortic valve. It is clinically undistinguishable from aortic insufficiency. Its prompt and precise diagnosis is crucial since early surgical treatment is definitely indicated, in contrast to aortic insufficiency. In our case, two-dimensional and pulsed color-flow Doppler imaging established the diagnosis, and the transesophageal approach was a great aid in detecting the aortic opening with its turbulent diastolic flow, and in tracing its intramyocardial course. This paper may be of interest not just as a new case-report but insofar as it stresses how importantly the transthoracic and transesophageal echocardiographic and Doppler scanning contributes to its diagnosis and therapeutic indication. PMID- 7792433 TI - [Utilization of angiotensin-converting enzyme inhibitors in anterior infarction without congestive semiology]. PMID- 7792434 TI - Nebulizer performance: AFLM study. Association Francaise de Lutte contre la Mucoviscidose. AB - This study was conducted by the AFLM order to determine the performance characteristics of 12 commercially available nebulizers (6 ultrasonic and 6 jet) used in the treatment of cystic fibrosis (CF). The nebulizers were connected to a circuit which simulated the ventilation of a CF child and CF adult, and were tested using three drug solutions: tobramycin (T), colistin (C), and amiloride (A). Nebulizer performance was evaluated according to the volume of drug solution delivered in 10 min during the simulated inspiratory phase (VI), drug granulometry (G%), drug concentration modification in the nebulizer reservoir (delta C), and percentage of efficiently aerosolized drug EA%). The ultrasonic devices delivered a significantly higher VI than the jet nebulizers (p < 0.0001) for all three study drug. Ventilation rate did not influence VI. Regarding granulometry, higher percentages of T and A were found to be contained in droplets ranging from 0.5 to 5.0 micron following ultrasonic nebulization. Drug concentration modifications were independent of the nebulizer used but were influenced by drug type; overconcentrations of T and A were observed (delta C = +10.5 +/- 18.6 and +13.4 +/- 8.9%, respectively). On average, the ultrasonic devices achieved a higher EA% than the jet nebulizers (17.3 +/- 6.7 and 9.7 +/- 9.6%, respectively). This study highlights the significant variability in performance of different nebulizer types and empahsizes the importance of accurately testing nebulizers prior to clinical use so that the most efficacious nebulizer/drug combinations may be prescribed. PMID- 7792435 TI - Aerosol administration of antibiotics. AB - Aerosol administration of antibiotics is an attractive approach to the treatment of the recurrent respiratory infections experienced by patients suffering from cystic fibrosis (CF). Through aerosol administration, drugs can, theoretically, be delivered directly to the target site of infection, i.e. the lumen of the lower respiratory tract, thus enabling smaller doses to be given. This, in turn, should result in reduced costs and decreased potential for systemic toxicity. The efficacy of aerosol antibiotic therapy is, however, influenced by numerous variables, including the type of nebulizer device used to deliver the aerosol, the drug's physical properties, its concentration in the aerosol and particle size, carrier gas and patient factors. The efficacy of aerosol antibiotics in the treatment of CF is controversial. This appears to be due mainly of problems and inconsistencies with clinical trials. However, various antibiotics, including beta-lactams, polymyxins and aminoglycosides, have demonstrated clinical benefits when administered by inhalation to CF patients. PMID- 7792436 TI - Physical and functional properties of airway secretions in cystic fibrosis- therapeutic approaches. AB - The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions. PMID- 7792437 TI - Proteases and antiproteases in cystic fibrosis: pathogenetic considerations and therapeutic strategies. AB - The association between abnormal chloride transport, resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, and the immunologic processes involved in the development of CF lung disease is poorly understood. However, neutrophil-dominated inflammation on the respiratory epithelial surface is a common finding in CF patients and suggests a mechanism for the immunologic abnormalities described in CF. Of particular importance for the pathophysiology of CF are proteases such as neutrophil elastase (NE) which are released from neutrophils in CF airways and cause direct structural damage to respiratory tissue. In healthy individuals, the deleterious effects of excess protease activity in the respiratory system are inhibited by antiproteases such as alpha 1 antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI). However, in CF, antiproteases are outnumbered by proteases and this protective mechanism is rendered ineffective. Restoration of this protease/antiprotease balance through antiprotease replacement therapy is currently under clinical investigation and preliminary results are promising. PMID- 7792439 TI - Quantitative methods for utilization of multi-source data in public health. Proceedings of a symposium. PMID- 7792438 TI - Clinical studies of rhDNase in moderately and severely affected patients with cystic fibrosis--an overview. AB - Clinical data are now available on the use of recombinant human DNase (rhDNase) in the treatment of CF patients with mild, moderate and severe pulmonary disease. Phase I studies were conducted and indicated the initial safety of rhDNase in humans. In the US phase II study, 181 patients with FVC > or = 40% were randomly allocated to receive rhDNase 0.6, 2.5, 10 mg, or placebo twice daily for 10 days. All three doses of rhDNase significantly improved FEV1 10-14% and FVC 10-12% compared to placebo. There was no significant increase in serious intercurrent events but a slight increase in pharyngitis and voice alteration. A phase II study including 71 patients was carried out in the UK. FEV1 improved by 13% from baseline compared to placebo. There was an improvement in CF-related symptoms and no increase in serious adverse events. The phase III double-blind placebo controlled study included 968 patients with FVC > or = 40% predicted. These patients were randomized to 2.5 mg rhDNase, once or twice daily, or placebo for 24 weeks. Compared to placebo, rhDNase-treated patients had a relative risk of protocol-defined respiratory tract infection reduced by 22 and 34% and improved FEV1 compared to baseline by 5.8% (p < 0.001) and 5.6% (p < 0.001), respectively, compared to placebo. A double-blind, short-term, placebo-controlled study in severely ill patients, FVC < 40% predicted, showed the drug to be safe but there was no significant improvement in lung function. After a further 6-month open label treatment, patients showed improvement in FEV1 and FVC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792440 TI - Meta-analysis: reconciling the results of independent studies. PMID- 7792441 TI - The development of the series of U.S. cancer atlases: implications for future epidemiologic research. AB - An historic perspective on the development of the National Cancer Institute's series of cancer atlases is provided. Emphasis is placed on the role which emergent questions concerning environmental determinants of cancer played in the acquisition and utilization of data resources. Studies which were fielded as a consequence of the atlases are highlighted. The legacy of the collective effort of many persons who worked on the development of the cancer atlases-the facilitation of many current epidemiologic investigations-is discussed. PMID- 7792442 TI - Linking public health data using geographic information system techniques: Alaskan community characteristics and infant mortality. AB - This article identifies geographical contexts important in differentiating infant mortality in Alaska and uses spatial processing models to link and analyse multi source data. Information characterizing geographical locations are collected from Alaska's vital statistics for the years 1982-91 and the 1990 Census. Geographic information system (GIS) techniques are applied to identify spatially homogeneous regions, assess spatial compatibility across databases, and allocate geographical units across boundaries. A primary goal of this paper is to encourage spatial linkage and analysis techniques for vital statistics and census data. By demonstrating the interplay of tabular, graphical, and mapping techniques on Alaskan infant mortality, this analysis describes procedures for conducting epidemiological research with data spatially defined at distinct geographical levels. PMID- 7792443 TI - Probabilistic linkage of large public health data files. AB - Probabilistic linkage technology makes it feasible and efficient to link large public health databases in a statistically justifiable manner. The problem addressed by the methodology is that of matching two files of individual data under conditions of uncertainty. Each field is subject to error which is measured by the probability that the field agrees given a record pair matches (called the m probability) and probabilities of chance agreement of its value states (called the u probability). Fellegi and Sunter pioneered record linkage theory. Advances in methodology include use of an EM algorithm for parameter estimation, optimization of matches by means of a linear sum assignment program, and more recently, a probability model that addresses both m and u probabilities for all value states of a field. This provides a means for obtaining greater precision from non-uniformly distributed fields, without the theoretical complications arising from frequency-based matching alone. The model includes an iterative parameter estimation procedure that is more robust than pre-match estimation techniques. The methodology was originally developed and tested by the author at the U.S. Census Bureau for census undercount estimation. The more recent advances and a new generalized software system were tested and validated by linking highway crashes to Emergency Medical Service (EMS) reports and to hospital admission records for the National Highway Traffic Safety Administration (NHTSA). PMID- 7792444 TI - Evaluating the quality of anonymous record linkage using deterministic procedures with the New York State AIDS registry and a hospital discharge file. AB - Linkage of same-person records across multiple databases relies on high-quality, uniformly available identifying information. These data quality issues become increasingly important when personal names are not available for record linkage. Using deterministic decision criteria, we linked records from two population based files in the absence of personal names. The sensitivity of anonymous record linkage procedures ranged from 32 to 85 per cent for the two years studied, and the positive predictive value (PPV) ranged from 14 to 99 per cent. Decreasing sensitivity and PPV were primarily attributed to (1) errors in computerized identifying information and (2) the deterministic decision criteria specified for record linkage. An evaluation of the contribution of personal names to the quality of record linkage found no measurable impact. PMID- 7792446 TI - On combining dose-response data from epidemiological studies by meta-analysis. AB - Using data from a meta-analysis of the effects of oestrogen replacement therapy on the development of breast cancer, we compared alternative methods for combining dose-response slopes from epidemiological studies. We evaluated issues related both to summarizing data from single studies and to combining results from multiple studies. Findings related to the analysis of individual dose response studies include: (1) a method of weighing studies that gives greater influence to dose-response slopes that conform to the linear relation of relative risk to duration can lead to large differences in calculated weights as a function of non-linearity; (2) a regression model using a variable-intercept resulted in a mean dose-response slope that increased as much as threefold when compared with the values obtained with a zero-intercept model. When combining results from multiple studies, we found: (1) calculating standard errors of mean dose-response slopes by methods that allow for both among-study and within-study variability (a random-effects type model) gave values different from a method that assumes homogeneity and equal within-study precision (a fixed-effects model); (2) the random-effects model gives mean and standard error results most similar to a bootstrap resampling method as increasing heterogeneity is observed (however, this model could give biased mean estimates compared with the bootstrap method); (3) a components-of-variance model compares favourably with the bootstrap and is easier to apply than the random-effects model. Based on these findings, we recommend the use of methods which incorporate heterogeneity to guard against underestimating the standard error. However, caution is urged because bias in point estimates can occur if extreme heterogeneity is present. Two other observations affect the interpretation of data combined from multiple studies. First, inclusion into a model of quality scores assigned by blinded reviewers had little effect on the mean dose-response slope and its standard error. Second, the number of studies required to achieve desired statistical power, varies with effect size. PMID- 7792445 TI - Verification of information in a large medical database using linkages with external databases. AB - Efforts to utilize Uniform Hospital Discharge Data Sets (UHDDS) for epidemiological studies have been hampered by the limitations of those databases. The purpose of this paper is to illustrate that linking to external databases can provide the verification necessary to overcome many of those limitations. This method has dramatically altered study design at the Connecticut Hospital Research and Education Foundation and has provided an efficient method for specifying data collection weaknesses within the resident databases. PMID- 7792447 TI - Meta-analytic approaches to dose-response relationships, with application in studies of lung cancer and exposure to environmental tobacco smoke. AB - This paper outlines several meta-analytic approaches to the assessment of quantal dose-response relationships; that is, to the evaluation of an increase in the level of exposure to an agent and the associated relative risk of a disease when this is investigated over a number of different studies. Analysis is developed at two levels: first, a consistent method of evaluating the dose-response relationship is applied to each study, and second, an overall picture is obtained by comparing and combining these relationships. At the first stage, for an individual study, dose-response assessment involves choices of model and appropriate tests for trend, which are influenced by such issues as dose measurement and use of the unexposed group. At the second stage, different methods for pooling results across studies must be considered. These depend on the choices made in the first stage of analysis, with additional attention paid to heterogeneity, and possible bias due to studies included in meta-analysis. We describe these meta-analytic approaches for three methods of evaluating dose response. The approaches are illustrated by evaluating the relationship between lung cancer and levels of exposure to environmental tobacco smoke (ETS). The strength of this relationship has been a point of debate in recent assessment of evidence for an overall carcinogenic effect of ETS exposure. We find little indication of a consistent dose response, a result explained in terms of recent models for cancer and passive smoking developed by Darby and Pike, the current meta-analysis results of overall risk-ratios of current studies in Tweedie and Mengersen, and misclassification models developed by the United States Environmental Protection Agency (EPA). PMID- 7792448 TI - A dual frame design for sampling elderly minorities and persons with disabilities. AB - Multiple data sources are sometimes available as potential sampling frames for population surveys, and in some situations the use of a multiple frame sample design is more advantageous than using a single sampling frame. The use of multiple sampling frames, however, has variance and bias implications, as well as sampling, data collection, and logistical considerations. These issues are addressed for a proposed dual frame sampling approach in the National Health Interview Survey (NHIS). The results of an investigation of the sampling efficiencies and operational issues in supplementing the NHIS area frame sample with a sample of elderly African and Hispanic Americans and persons with disabilities selected from Social Security Administration files are presented. PMID- 7792450 TI - Development and applications of a city-level alcohol availability and alcohol problems database. AB - Data on alcohol availability and problems in all cities in Los Angeles County were collected from several different sources and linked together to form a Local Alcohol Availability Database (LAAD). The two major purposes of the project are to provide a city-level alcohol availability and alcohol-related problems database needed by local community alcohol policy planners and to collect the data necessary for research on the relationship between these measures. The prevalence of drunk driving arrests is displayed on a map. We describe how the LAAD has been used to guide alcohol policy decisions. A fixed year and city effects regression model suggests that outlet density is positively related to several alcohol-related problems. PMID- 7792451 TI - Feasibility of contour mapping epidemiological data with missing values. AB - Data of epidemiologic interest often occur as spatial information during each of several time periods. In most cases data are available from a set of regions or localities which can be viewed as points in a plane. Although contour mapping is useful for displaying these data, the lack of data for all data points in a region may lead to erroneous interpretation. In this paper we use stimulation to investigate the impact of missing data points for contour mapping using two distinct simulated spatial-time distributions for epidemiologic variables. A model for the occurrence of malaria in localities randomly distributed in one region is chosen as the prototype for data generation. PMID- 7792449 TI - Multiple hypothesis tests in multiple investigations. AB - Inferential statistical methods have traditionally been based on the assumption that one experiment is performed and that interest centres on one or more predetermined hypothesis tests. Exploratory research, on the other hand, often involves multiple hypotheses or repeated investigations under similar or different conditions or both. Several techniques have been proposed to deal with multiple or simultaneous hypothesis testing in single investigations, and procedures to combine observed significance levels for an individual hypothesis test from two or more investigations have been suggested. In this paper we propose a method for identifying important results from multiple statistical tests in multiple investigations. The method is illustrated by using high performance liquid chromatography to identify potential aetiologic contaminants in L-tryptophan samples. PMID- 7792452 TI - Effects of the choice of age-adjustment method on maps of death rates. AB - Maps of morbidity or mortality rates, whether considered individually or as a layer in a geographic information system application, invite multiple comparisons of area rates. However, comparisons of rates across different populations require standardization of the age-specific rates to account for differences in population age structures. The indirect standardization method, or equivalently the standardized mortality ratio (SMR), has been recommended for small areas where age-specific rates can be quite variable. Although theoretically equivalent to directly adjusted rates under the assumption of independent age and area effects, indirect summary measures are not comparable across areas when this assumption is violated. We tested the validity of this assumption for the 10 most common causes of death in the United States during 1980-84 and examined the geographic clustering apparent when categorized death rates, adjusted by different methods, are presented as thematic maps. Although overall agreement between the methods was good (rank correlation coefficient > 82 per cent for each cause), when the adjusted rates were classified into quintiles 18 per cent of the states fell into different categories depending on the method of adjustment. Using an internal standard for the indirect method reduced this discrepancy to 4.9 per cent. However, both traditional chi-square tests and a generalized logistic spline model identified significant interactions between age and area for each cause of death, a violation of the assumption required for equivalence of the methods. Potential variation in geographic inferences is illustrated by maps of direct and indirect rates and an empirical Bayes posterior mean, which is a function of these traditionally adjusted rates. Based on these results, we recommend the direct age-adjustment method for rate maps. PMID- 7792454 TI - Differences in morbidity measures and risk factor identification using multiple data sources: the case of coronary heart disease. AB - The NHANES I Epidemiologic Followup Study contains several sources of information that can be used to define case status. Incidence rates and relative risks associated with selected, documented risk factors for heart disease were estimated using nine different case definitions. Despite wide variation in the estimates of incidence, the characteristics of the cases were remarkably similar as were the risks associated with heart disease incidence. The main difference occurred when cases were defined on the basis of death certificate information. Cases defined this way are more severe and models based on this definition result in relative risks of greater magnitude. PMID- 7792455 TI - The price and purity of cocaine: the relationship to emergency room visits and death, and to drug use among arrestees. AB - This paper examines the relationship of the price and purity of cocaine to emergency room visits and deaths associated with cocaine use and to cocaine use among arrestees. A model is developed for the trend in cocaine prices at the retail level during the period January 1986 to December 1991. This trend is then compared to information on emergency room visits, medical examiner reports, and the percentage of arrestees testing positive for cocaine use over the same period. The principal conclusion is that there is a significant negative relationship between the estimated street price of cocaine and the level of related medical emergencies and deaths and the number of arrestees who test positive for cocaine. PMID- 7792453 TI - Public health surveillance for chronic conditions: a scientific basis for decisions. AB - In this paper we investigate the important contribution of multiple public health surveillance systems to policy in chronic disease control and prevention. We show that, typically, surveillance for chronic diseases relies on multiple data sources, often created for another purpose. We also define the concept of burden for chronic conditions based on data from multiple sources. An example from a state illustrates a model for combining data for use in policy development. These applications illustrate the central role of statistical methods in ensuring the appropriate use of data from multiple surveillance systems. PMID- 7792456 TI - Combining National Health Interview Survey Datasets: issues and approaches. AB - This paper identifies issues, special problems, and approaches in preparing estimates when combining National Health Interview Survey (NHIS) datasets. Such datasets can be used to produce estimates jointly based on individual NHIS survey components. This paper illustrates several issues associated with the analysis of multiple related datasets. PMID- 7792457 TI - Meta-analysis for dose-response models. PMID- 7792458 TI - Data linkage. PMID- 7792459 TI - Utilization. 1: special datasets. PMID- 7792460 TI - Utilization. 2: special datasets. PMID- 7792461 TI - Study design and public health planning. PMID- 7792462 TI - Methodologic issues. PMID- 7792463 TI - [Progress in hepatitis diagnosis]. AB - Until today only five pathogens of viral hepatitis have been discovered: hepatitis virus A (HAV), B (HBV), C (HCV), D (HDV) and E (HEV). An update on the state of the art of actually established diagnostic procedures is briefly summarized. Some recent topics and problems are covered more extensively; in the case of HBV the value of HBsAG concentration as a prognostic marker, the finding 'anti-HBc only' the role of HBV mutants, the determination of circulating HBV genomic material, and modalities for HBV vaccination control; in the case of HCV the indications for study of its viral genomic material and the role of HCV subspecies are explained. Finally, first results on HEV prevalence in Switzerland are introduced. PMID- 7792464 TI - [Portal hypertension]. AB - Portal hypertension is a frequent and dangerous consequence of chronic liver diseases. The most important complications are ascites and variceal bleeding. In this article new pathophysiological theories of portal hypertension are reviewed. In addition, the prophylactic and therapeutic management of variceal bleeding are discussed. PMID- 7792465 TI - [Therapy in hepatic ascites]. AB - This is a review on the pathogenesis, precipitating causes, analyses, complications, prognosis and therapeutic possibilities of hepatic ascites for practical purposes. Among the possible analyses, granulocyte count, difference between serum albumin and ascitic albumin, cytologic evaluation and bacterial culture in blood-culture media are the most promising. Spontaneous bacterial peritonitis often shows no local clinical signs and carries a bad prognosis, unless looked for and treated. The hallmark of treatment of hepatic ascites consists of reduced sodium intake, diuretics and total paracentesis. Peritoneovenous shunt, TIPPS and hepatic transplantation are options in refractory cases. PMID- 7792466 TI - [Dyspepsia: work-up or provisional treatment?]. AB - Dyspepsia is defined as symptoms that are considered by a physician to originate from the upper gastrointestinal tract. The term 'functional dyspepsia' designates dyspepsia after exclusion of organic causes. Dyspepsia is a frequent problem in general practice. Mainly for economical reasons, it is impossible to perform every available diagnostic test in every patient to exclude all possible organic causes. The initial work-up is directed at identifying alarm symptoms and alarm signs from history, physical examination, and simple laboratory tests. The presence of any alarm symptoms or alarm sign requires prompt investigation. If none can be found, empirical drug treatment may be performed according to the leading symptom. Treatment failure or rapid recurrence require additional investigations, in particular by gastroscopy. PMID- 7792467 TI - [Gastroduodenal ulcer disease: update on pathogenesis]. AB - Gastroduodenal ulcer disease comprises a heterogeneous group of different diseases resulting uniformly in a mucosal defect reaching beyond the muscularis mucosae. Consequently, a single unifying pathogenesis of ulcer disease does not exist but only a rather general concept that ulcers develop when mucosa-injuring factors outweigh the mucosa-protecting factors. According to this concept, ulcers develop within a broad range of different possibilities in the relation of mucosa injuring factors to impaired mucosal protection. The main histological and physiological elements for the understanding of peptic ulcer disease are briefly summarized, followed by a short survey of the important known 'traditional' abnormalities of possible pathogenetic importance in duodenal and gastric ulcer patients. Gastroduodenal ulcer disease represents a typical example of a multifactorial disease, where different combinations of both hereditary and environmental factors produce the same morphological lesion. By far the most exciting data of the last ten years originate from the still increasing understanding of the role of Helicobacter pylori in gastroduodenal ulcer disease. The most important evidence and hypotheses are presented of how and where Helicobacter pylori is or could be involved in the complicated pathogenetic network of ulcer disease. The infection of gastric epithelium by Helicobacter pylori has become the second main factor besides acid/pepsin in the pathogenesis of ulcer disease. Beside the improved insights in ulcer pathogenesis, the translation of the new data into clinical medicine has led and will lead to remarkable progress. Most important: a causal therapy of ulcer disease has become available in contrast to the so far practiced sole symptomatic treatment of single ulcer episodes. What has treatment of single ulcer episodes. What has been a domain of ulcer surgery has come into reach of drug therapy. PMID- 7792468 TI - [Psychosocial aspects of the climacteric]. AB - Medicine has till now payed less attention to psychosocial aspects of the menopause than to the hormonal changes of woman in this period of life. The climacteric woman is characterized in the language of the organ-medicine by faulty terms. The lack of hormones is considered to be a disease which has to be treated. The tendency to medicalize the menopause is in contradiction to the results of recent prospective studies. These studies show that pre- and postmenopausal complaints are less severe than they are often described. Psychosocial risk factors before and during the climacteric phase favour the development of psychic and psychosomatic symptoms. The climacteric period of life has to be seen as a vulnerable time of life which should be considered in the treatment of menopausal women. PMID- 7792469 TI - [Pharmacotherapy of sleep disorders using benzodiazepine hypnotics and their analogs]. AB - Benzodiazepine hypnotics and analogs promote the inhibitory neurotransmitter GABA in the brain. The individual substances of this class differ mainly with respect to their elimination half-life. They are all effective hypnotics, but exhibit a number of undesired effects. Hypnotics should be administered generally for the short-term treatment of insomnia, and they should be prescribed for a prolonged time period only exceptionally. PMID- 7792470 TI - [Female incontinence: work-up and therapy]. AB - Female incontinence is a more frequent disorder than sometimes realized. The patient should be asked about urinary incontinence symptoms. Depending on her degree of suffering, the appropriate diagnostic examinations and therapy can be chosen. With simple procedures, such as anamnesis, gynecological examination with testing, Valsalva maneuver with a full bladder, and a review of miction diaries, the kind of incontinence can be reliably determined, and first therapeutic steps can be initiated. For stress incontinence this would be pelvic floor reeducation or physical therapy with electric stimulation and bio-feed-back; only if these conservative measures fail, one should operate. For urge incontinence, it is important to strive for a change in drinking and miction habits (bladder training), i.e., to increase the amount of liquid intake and the miction volume (checked by miction diaries). This therapy can be further supported by medication. Urodynamic diagnostic examinations are indicated when primary therapy (pelvic floor reeducation, bladder training) fails, before any incontinence operation and when the type of incontinence is not clear. PMID- 7792471 TI - [Sleep apnea syndrome and morbid snoring]. AB - Regular, continuous snoring usually does not have any sleep disturbing effects; however, discontinuous snoring may be associated with increased upper airway resistance and leads to recurrent arousals, sleep fragmentation and excessive daytime sleepiness. Loud snoring, recurrent obstructive apneas and oxygen desaturation during sleep with excessive daytime sleepiness are the hallmarks of the obstructive sleep apnea syndrome (OSAS). A tentative diagnosis of disturbed breathing during sleep can be made from a careful history and confirmed by a sleep study. Continuous positive airway pressure (CPAP) applied by a nasal mask is the primary treatment for OSAS and for snoring associated with increased upper airway resistance and symptoms of sleep disruption. CPAP may improve sleep quality, excessive daytime sleepiness, and potentially vascular morbidity and mortality among patients with severe OSAS. PMID- 7792472 TI - [Cerebellar ataxia with autosomal dominant transmission]. PMID- 7792473 TI - [Radiation-induced neuropathies. Experimental and clinical data]. AB - In contrast with the central nervous system, the peripheral nerves are usually considered radioresistant. However, experimental and clinical data show evidence of peripheral nerve injury after radiation therapy. The physiopathology remains unclear. Vascular alterations appear to play an important role. Direct damage to axon or Schwann cell and nervous compression in areas of radiation fibrosis could also be involved. Clinically, brachial plexopathy is a well-recognized complication but all the structures of the peripheral nervous system can be involved: cranial nerves, roots, plexus and nerve trunks. A syndrome of early and reversible plexopathy differs from the classical progressive form with pejorative outcome. Radiation-induced peripheral nerve tumors are infrequent. PMID- 7792474 TI - [Cerebral localizations before Charcot]. PMID- 7792475 TI - [A study network of human spongiform encephalopathies: 1st results]. AB - Several French teams including clinicians and researchers have created a group within the European network for the study of Creutzfeldt-Jakob disease and other human spongiform encephalopathies. The main objectives are to monitor the incidence of the disease and to search for possible risk factors with a case control study. The diagnosis is based on neuropathological studies or the identification of an abnormal protein prion in cerebral fragments. The sequence of the gene encoding for the prion protein has was studied from blood or cerebral samples. The early results indicate that the incidence, mortality and clinical presentation remain relatively constant compared with earlier studies. Studying the expression of the 129 codon of the prion protein gene has led to the verification that homozygous methionine/methionine forms predominate in sporadic forms. PMID- 7792476 TI - [Mitochondrial encephalopathies with late disclosure and predominant involvement of central nervous system]. AB - We report three cases of mitochondrial encephalomyopathy affecting predominantly the central nervous system; two patients had the MELAS syndrome and one had "ophthalmoplegia plus". Histoenzymatic analysis of muscle biopsy and biochemical studies of muscle mitochondria demonstrated myopathy associated with partial deficiency of complex I of the electron transfer chain in three cases, complex IV in two cases and complex III in one case. Molecular analysis of mtDNA in the first case did not revealed any abnormality. Coenzyme Q10 therapy improved exercise tolerance but not the central nervous signs. PMID- 7792477 TI - [Leptomeningeal gliomatosis. 2 clinicopathological cases]. AB - Leptomeningeal gliomatosis is a diffuse glial infiltration of the subarachnoid space. It is primary and very rare when primary astrocytoma arises in the leptomeninges from heterotopic neuroglial tissue; it is secondary and more frequently reported when associated with a medullar or cerebral intraparenchymal astrocytoma and secondary involvement of the leptomeninges. Primary and secondary forms are difficult to differentiate before neuropathological examination. The authors report 2 anatomo-clinical cases of leptomeningeal gliomatosis in adults, with clinical courses of 6 months and 40 days respectively. The initial clinical picture was aseptic chronic or subacute meningitis. Cytologic examinations of the cerebrospinal fluid (CSF) showed moderate lymphocytosis, with elevated protein and low glucose levels, without abnormal cells. On case 2 CT scan and in case 1 spinal MRI isolated diffuse meningeal contrast enhancement was present, without intraparenchymal lesion. The neuropathological study revealed a diffuse astrocytoma glial leptomeningeal tumour with a focal involvement of the central nervous system (spinal cord in one case, temporal lobe in the other). In conclusion, an isolated aseptic lymphocytosis meningitis with meningeal abnormal signal may reveal leptomeningeal gliomatosis. Neuropathological examination can distinguish primary from secondary forms. PMID- 7792478 TI - [Subacute leukoencephalopathy of the rhombencephalon after pituitary radiotherapy]. AB - Two patients had early delayed leucoencephalopathy mainly confined to the brainstem after radiotherapy for pituitary tumours. To our knowledge, we report the first MRI description. The patients had somatotroph cell adenomas (associated with prolactin secretion, patient 2). Surgical removal of the adenomas were complete (patient 1) and partial (patient 2). Both underwent pituitary irradiation: patient 1, 55.8 Gy (31 x 1.8 Gy); patient 2, 54 Gy (27 x 2 Gy). Six weeks after completion of radiation, the patients had low vigilance, sleepiness, cerebellar symptoms, optic neuropathy (patient 1), CSF inflammatory reaction. T2 weighted MRI scans showed hypersignal in brainstem, cerebellar peduncles (both patients), temporal lobe white matter (patient 2). T1-weighted images showed hyposignals, pseudonecrotic and contrast-enhanced images in brainstem (patient 1). Both patients responded to intravenous then oral steroid treatment with a progressive and complete clinical recovery. Radiological abnormalities improved with clinical statement. Present characteristics support a demyelinating mechanism of early delayed cerebral radiation injuries. PMID- 7792479 TI - [Cerebral cysticercosis treated by albendazole: development of cerebral magnetic resonance imaging]. AB - A 36-year-old Indian man presented with a generalized tonic-clonic seizure. The diagnosis of neurocysticercosis was suspected by the presence of multiple cystic and nodular cerebral lesions on MRI, and was confirmed by serological studies (ELISA). He was treated with albendazole during one week at the daily dose of 15 mg/kg. This case illustrates the advantage of MRI over CT for the detection and the therapeutical follow-up of neurocysticercosis. Moreover, the MRI findings can be correlated to the anatomical stage of neurocysticercosis, proposed by Escobar (1983); four stages are described: I = vesicular stage (living larvae), II = vesicular colloidal stage (degenerating larvae), III and IV, granular nodular and nodular calcified inactive stages respectively. PMID- 7792480 TI - [Spinal dural fistula with peri-medullar venous drainage]. AB - Clinical and neuroradiological findings of 8 patients with a spinal dural arteriovenous fistula are reviewed. Disturbance of micturition or defecation and weakness of the legs were always present and the most frequent initial symptom was a progressive spastic paraparesis. Duration of symptoms before diagnosis was 2 years. Lumbar puncture showed elevation of proteins and myelography demonstrated dilated perimedullar posterior veins. In every case, magnetic resonance imaging of the spinal cord (T2- weighted images) revealed intramedullary high signal intensity of the conus medullaris and selective angiography confirmed the site of the dural fistula. Each patient was treated with endovascular method consisting in liquid adhesive embolization (0.2 cc of N butyl cyanoacrylate) with hyperselective catheterism of the dorsospinal artery. Embolization procedure was successful in 6 cases with large improvement of leg weakness and partial regression of disturbed micturition and defecation. The pathophysiological mechanisms explaining the clinical signs are discussed. PMID- 7792481 TI - [Nocturnal orthosis: a new treatment of compression of the ulnar nerve at the elbow. 30 cases]. AB - Compression of the ulnar nerve at the elbow was confirmed by electromyography in 30 patients including 29 cases of idiopathic aetiology and 1 case of late onset ulnar palsy. Six cases occurred after general anaesthesia and 3 had undergone an unsuccessful operation. All patients were managed solely with an orthesis worn at night. The orthesis held the elbow in 60 degrees flexion. Clinical improvement was noted in all cases (including the 3 cases of unsuccessful surgery) evaluated by the patient and the physician at 88% on the average. Improvement occurred rapidly and was evaluated at 50% on day 15 in 9 out of 10 patients seen on this day. The level of improvement was directly related to regular use of the orthesis. Seven electromyographic criteria were measured and nerve conduction speed was 33.0 m/sec (motor and sensory) and improved significantly by 7.3 m/sec (motor) and 9.5 m/sec (sensory) in all cases but one (p < 10(-8)). In conclusion, this simple non-invasive management protocol is not a simple symptomatic treatment but helps restore nerve function. The effectiveness of this method suggests that nocturnal position plays a major role in impairment due to compression of the ulnar nerve. PMID- 7792482 TI - [Multiple and recurrent paralysis of cranial nerves: primary Gougerot-Sjogren syndrome]. AB - Over a period of 10 years, a 49-year-old man had 3 episodes of recurrent cranial nerve palsy regressing within a few weeks. Each episode was accompanied with acute inaugural headache and diplopia and once with sensory impairment of the trigeminal nerf and once with tinnitus. The diagnosis of Goujerot-Sjogren's syndrome was retained after demonstration of hypergammaglobulinaemia, a positive Rose Bengale test and histological examination of biopsy specimens from the accessory salivary glands which revealed advanced typical lesions. Clinically, impaired secretion was not obvious. PMID- 7792483 TI - [Acute motor axonal neuropathy with favourable outcome after Salmonella Ohio infection]. AB - We report one patient presenting an acute weakness following an infection with Salmonella Ohio. Diagnosis was Guillain-Barre syndrome (GBS). However, preservation of reflexes and electrophysiological study showing purely axonal pattern make this case different from typical GBS. Outcome was favourable. There are probably various forms of GBS and the axonal form do not always carry a bad prognosis as previously reported. PMID- 7792484 TI - [Case presentation at Salpetriere Hospital, March 1993. Bucco-facial dyskinesis, memory disorder and psychomotor inertia in a 52-year-old man]. PMID- 7792485 TI - [Charcot-Marie-Tooth disease type II and dopa-sensitive Parkinson syndrome]. PMID- 7792486 TI - [Study of 82 cases of infarction in the posterior cerebral arteries]. PMID- 7792487 TI - [Post-traumatic inter-hemispheric disconnection syndrome]. PMID- 7792489 TI - Dreams and rapid eye movement sleep in the multiple sleep latency test. AB - Dreams are closely associated with rapid eye movement (REM) sleep. The purpose of this study was to evaluate the reliability of dreams in predicting the presence of REM sleep during naps of the multiple sleep latency test (MSLT). We prospectively analyzed MSLTs performed in the evaluation of 44 patients with excessive daytime sleepiness. A total of 167 naps were studied. The patients' ages ranged from 11 to 69 years (mean 45 years). There were 26 males and 18 females. The relationship between the presence of reported dreams and the presence of REM sleep was as follows: sensitivity (percentage of naps with REM in which dreams were reported), 59%; specificity (percentage of naps without REM in which no dreams were reported), 63%; positive predictive value (probability that REM occurred if dreaming is present), 29%; and negative predictive value (probability that REM did not occur when no dreaming is present), 85%. In the daytime naps of the MSLT, the presence of reported dreaming did not appear to be a reliable indicator of the presence of REM sleep in the preceding nap. PMID- 7792488 TI - [Sclerosis with benign plaques with childhood onset]. PMID- 7792490 TI - Sleep disturbance in elderly patients with cognitive impairment, decreased daily activity and periventricular white matter lesions. AB - We investigated how sleep disturbance is correlated with brain lesions, cognitive impairment and decreased daily activity (ADL). Two hundred and four chronically ill patients including patients with vascular dementia were classified into eight groups based on cognitive function, ADL and grades of PVL (periventricular lucency) as shown by computerized tomography. Visual monitoring of the sleep/wake state was performed hourly for 14 consecutive days and the daytime sleep hours and the nighttime sleep hours were determined based on detected disturbances in the sleep/wake pattern. Whether any specific infarcted regions were correlated with sleep disturbance was also evaluated. We found that daytime sleep hours were increased and nighttime sleep hours were decreased by three single factors: cognitive impairment, decreased ADL and the severe grade of PVL. As for an interactive effect of the two factors, daytime sleep hours were increased by dementia with decreased ADL (independent of PVL) and increased by decreased ADL with the severe grade of PVL (independent of dementia). Although three factors affected sleep independently, ADL has an interactive effect on sleep with dementia and with PVL. No specific cortical regions related to sleep disturbance were found. PMID- 7792491 TI - Assessment of accuracy and analysis time of a novel device to monitor sleep and breathing in the home. AB - Obstructive sleep apnea is increasingly recognized as a common and debilitating disorder. As a result, a variety of diagnostic technologies have evolved to potentially decrease cost and improve access and ease of assessment. In this study we compared the Healthdyne NightWatch (NW) System (a home sleep diagnostic methodology) to standard polysomnography (PSG) in two sleep centers. Two separate studies were completed. NW was compared to a simultaneously obtained PSG in 30 patients (IN-LAB study). Seventy additional patients were studied in both the home with NW and in the laboratory with PSG (HOME-LAB study). The NW system records eye movement, leg movement, SaO2, nasal-oral airflow, chest and abdominal wall motion, body position and heart rate on a solid state recorder, which permits sleep staging based on body and eye movement and standard respiratory assessment. For the PSG, standard paper recording techniques were used. The IN LAB study revealed a correlation between NW and PSG for total sleep time of r = 0.72, with NW tending to score some awake time as nonrapid eye movement sleep. The correlation for apnea-hypopnea index (AHI) was r = 0.94 between systems, with a sensitivity of 100% and specificity of 63.6% at an AHI threshold of 10. The HOME-LAB study demonstrated understandably poor correlations between NW and PSG for most measures of sleep, which is likely a product of night-to-night variability in sleep, home versus laboratory effects and the differences in sleep staging methodology. However, the correlation for AHI was r = 0.92, with a sensitivity of 90.7% and a specificity of 70.4% at an AHI threshold of 10. Using a new methodology to assess agreement between diagnostic systems, we observed 78.6% diagnostic agreement between NW and PSG in the HOME-LAB study, with NW underestimating AHI 4.3% of the time and overestimating it in 17.1% of cases. This may relate to night-to-night variability in AHI or greater NW computer sensitivity to subtle hypopneas. We conclude that NW provides an accurate determination of AHI in both the home and laboratory, using limited instrumentation. The analysis time for NW is also reduced compared to PSG, and patients generally prefer the NW evaluation. PMID- 7792492 TI - Gender- and age-related differences in sleep determined by home-recorded sleep logs and actimetry from 400 adults. AB - Home-based sleep was monitored by morning logs and wrist actimetry for 15 nights in a sample of 400 adults (20-70 years old; 211 female, 189 male; one per household). Subjects on sleep-enhancing medications and/or whose sleep was severely disturbed by illness were excluded. Subjects were grouped into age bands: ("young" = 20-34 years, "mid-aged" = 35-49 years and "older" = 50-70 years). Women retired to bed and fell asleep earlier than men. Men and women woke up earlier with increasing age. Sleep period time was markedly longer for women. Most reported awakenings were < 5 minutes. Women reported more awakenings, more total time spent awake during the night and poorer sleep quality; all these findings were most evident in the older women, who also took longer to fall asleep than any other group. Although these age effects are consistent with those reported elsewhere, the gender effects, some of which are much stronger than the age effects, have not been so evident before. PMID- 7792493 TI - Portable recording to assess the severity of obstructive sleep apnea: a European perspective. PMID- 7792494 TI - Guidelines for in-home testing: a need for reassessment. PMID- 7792495 TI - Behavioral state organization in normal human term fetuses: the relationship between periods of undefined state and other characteristics of state control. AB - Repeated alteration in episodes of quiet sleep and active sleep is a basic feature of behavioral state organization in human fetuses. When compared to normal fetuses, at-risk fetuses generally exhibit extended periods of no coincidence (PsNC), that is, associations between state variables that cannot be classified as a sleep state. The purpose of this study was to determine if fetuses with extended PsNC differ in other state measures from fetuses with short PsNC. Fetal heart rate and fetal eye and gross body movements were collected simultaneously on 85 normal human fetuses between 37 and 41 weeks gestation for a total of 9,135 minutes (mean 108.8 +/- 12.7 minutes, range 85-130 minutes). We found that as percent PsNC increased, the frequency (r = 0.464, p < 0.0001) of state changes increased and the time spent in active sleep (r = -0.456, p < 0.0001) and the number of fetuses entering an awake state (chi 2 = 4.26, p < 0.039) decreased. In contrast, percent PsNC was independent of the length of time spent in quiet sleep (r = 0.070, p > 0.05). We interpret these findings as an indication that extended PsNC may be the result of disruption of homeostatic control mechanisms during active sleep. PMID- 7792496 TI - Naps in children: 6 months-7 years. AB - A cohort of 172 children was followed from 6 months to 7 years of age to determine how nap patterns change with age and whether there was individual stability of nap patterns. Results showed that there were no differences in nap patterns based on gender, ordinal position, whether naps spontaneously disappeared or were stopped by the parents, and the number of naps at 6 months of age. Total daytime sleep remained a stable individual characteristic between 6 and 18 months of age. Age was associated with hours napping (r = -0.73, p < 0.001) and number of naps (r = -0.52, p < 0.001). A pattern of two naps per day was well established by 9-12 months of age and one afternoon nap by 15-24 months. The modal duration of naps from 2 to 6 years was 2 hours. During the 3rd and 4th year, napping occurred in the majority of children, but at decreasing rates. A minority of children were napping at 5 and 6 years and naps usually disappeared by age 7. PMID- 7792497 TI - Effects of flurazepam and zolpidem on the perception of sleep in normal volunteers. AB - In previous studies we have reported that the benzodiazepine hypnotic triazolam and the nonbenzodiazepine zolpidem increase the likelihood that insomniacs will report having been asleep when awakened by an electronic tone of progressive intensity. It has not been known, however, whether this occurs with normal sleepers. In the present study we have administered placebo, flurazepam 30 mg and zolpidem 10 mg to 15 normal sleepers and awakened them with an electronic tone at five points across the night. In contrast to previous reports with insomniacs, both compounds made only modest improvements in sleep. When all time points were combined, subjects reported having been asleep in 40.3, 42.9 and 47.9% of the trials on placebo, flurazepam and zolpidem, respectively (ns). Subjects were accurate in their estimate of total time asleep, and this accuracy was not influenced by the drugs. Similarly, there were no effects on a variety of questions related to dreaming and other cognitive activity during sleep. These results suggest that the effects of these hypnotics, which have been described previously in insomniacs, are not found in normals. Further studies will be necessary to clarify whether such effects in insomniacs are related to the clinical efficacy of hypnotics. PMID- 7792498 TI - Effects of flurazepam and zolpidem on the perception of sleep in insomniacs. AB - We have shown previously that the benzodiazepine hypnotic triazolam alters the perception of being awake or asleep in insomniacs, making it more likely that they will report having been asleep when awakened by an electronic tone at various times of the night. In the present study, we examined the question as to whether this is also true for other benzodiazepines as well as for nonbenzodiazepine hypnotics. Ten insomniacs were given placebo, flurazepam 30 mg and zolpidem 10 mg and were awakened at five times during subsequent sleep in a random-sequence repeated-measures study. Across all five awakenings following placebo, insomniacs reported being asleep with a frequency of 30.9%. This rose to 40.4% (ns) and 54.7% (p < 0.03) on flurazepam and zolpidem, respectively. Subjects were also more likely to report having been dreaming during the awakening 5 minutes after "lights out" after receiving zolpidem. A number of polygraphic measures of sleep, including sleep latency, total sleep and sleep efficiency, improved significantly on both drugs, and there was similar improvement in some global measures of quality of sleep. Neither drug altered the subjective sense of duration of time. These findings suggest that drug-induced alterations in the perception of being awake or asleep are not unique to benzodiazepines, but occur with the nonbenzodiazepine zolpidem as well. PMID- 7792500 TI - [Professional development in participating health organizations]. PMID- 7792499 TI - The use of caffeine versus prophylactic naps in sustained performance. AB - Previous studies have shown that performance during sleep loss is improved by prophylactic naps as a function of varying nap length. Based on single-dose caffeine studies, a similar dose-response effect has been hypothesized on performance, alertness and mood during sleep loss. The present study compared the effects of repeated versus single-dose administration of caffeine and varying amounts of sleep taken prior to sleep loss on performance, mood and physiological measures during 2 nights and days of sleep loss. A total of 140 normal, young adult males participated at one of two study sites. Ninety-eight subjects at one site were randomly assigned to one of four nap conditions (0, 2, 4 or 8 hours) and 42 subjects at the second site were assigned to one of four caffeine conditions. After a normal baseline night of sleep and morning baseline tests of performance, mood and nap latency, subjects in the nap groups returned to bed at noon, 1600 hours, 1800 hours or not at all. Bedtimes were varied so that all naps ended at 2000 hours. Subjects in the caffeine groups received either a single 400 mg dose of caffeine at 0130 hours each night or repeated doses of 150 or 300 mg every 6 hours starting at 0130 hours on the 1st night of sleep loss. A placebo control group (no nap and placebo administered every 6 hours on the repeated caffeine schedule) was run at both sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792501 TI - [Back pain]. PMID- 7792502 TI - [History of nursing. "Rules from 1417". Hospital of Santa Creu of Barcelona]. PMID- 7792503 TI - [Meningomyelocele and surgery of scoliosis]. PMID- 7792504 TI - [Continuous hemofiltration. A technique on the rise]. PMID- 7792505 TI - [Continuing education. What to do about a rise in intracranial pressure]. PMID- 7792507 TI - Prostate cancer: the pros and cons of treatment. PMID- 7792506 TI - Take the pain out of CPR training. PMID- 7792508 TI - When pain cuts to the bone. PMID- 7792509 TI - Insulin therapy. PMID- 7792510 TI - Working with a new staff mix. PMID- 7792511 TI - Neuromuscular blockade: when paralysis is intentional. PMID- 7792512 TI - The basics of therapeutic touch. PMID- 7792513 TI - When language is an obstacle. PMID- 7792514 TI - Write it down. PMID- 7792515 TI - UAPs or not ... PMID- 7792516 TI - [Accumulation of heavy metals (Pb, Cd) in selected varieties of vegetables]. AB - Vegetables have a great share in supplying of lead and cadmium with food into the human organism. For this reason an attempt was undertaken for quantitative evaluation of accumulation of those metals in three varieties of the following vegetables: carrots, parsley, garden beet, cabbage and potato grown at identical fertilization, weather conditions and pollution. Cadmium and lead were complexed with diethyldithiocarbamate, extracted into organic phase, and determined using atomic absorption spectrometry method. Cadmium content in tested vegetables was close to allowed values, established by Polish Legislation for these foods stuffs, and even exceeded limits in many specimens. Lead content is lower than allowed values with exception of one variety of carrot and all parsley specimens (leaf). Statistically significant differences (t-Student test) in the content of lead and cadmium in different varieties of the same vegetable were not observed. However, the minimum content of both metals in cultivated vegetables was observed in the following vegetables: parsley, carrot (three varieties), red beet (two varieties), potato, cabbage (two varieties). PMID- 7792517 TI - [Simultaneous determination of metals in milk by the ICP-AES technique]. AB - The method of the emission atomic spectrometry with an excitation in the inductively coupled plasma (ICP-AES) has wide range of applications due to the possibility of the simultaneous determination of several elements in various materials. This technique allows to carry out a multi-element analysis at relatively low consumption of the sample which is an additional advantage of the method. In this paper we report an application of the ICP-AES method for a direct determination of the element Al, Cu, Fe, Mn, Sn and Zn in the samples of milk. Several types of pressure mineralization (teflon bomb, sealed quartz tubes) as well as the pressureless technique with the use of the H2SO4, HNO3 and H2O2 agents have been studied. The determinations have been carried out with the use of the Spectroflame M sequential spectrometer with the excitation in ICP plasma made by Spectro Analytical Instruments at the Frequency of 27.12 MHz. The milk samples after mineralization have been diluted to the same volume and directly introduced into the ICP plasma with the help of the pneumatic nebulizer of Meinhard type. On the basis of the obtained results it has been concluded that with an application of the aforementioned mineralization method the average values for the determination of the particular elements are comparable. Generally the most "repeatable" results have been obtained for the sample mineralized in the quartz tubes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792518 TI - [Content of micro- and macro-elements, lead and cadmium in albumins and globulins of fresh and stored, dried seeds of the Faba bean]. AB - The content of micro/macroelements, lead and cadmium in Faba bean proteins from the seeds after their harvest and from the seeds stored (2 months, 6-8 degrees C) and dried (6h at 35 degrees C up to 15-15% moisture) was determined. Proteins were extracted with water (pH 8.0). Globulins were precipitated from water protein extract at pH 4.2. The microelements (Cu, Mn, Fe and Zn) content in albumins and globulins from the seeds after their harvest and from stored and dried seeds were as follows: 37.4 and 27.1; 46.7 and 35.8; 15.4 and 18.9; 179.2 and 229.7 micrograms/g (albumins) and 24.9 and 31.9; 20.0 and 28.1; 92.1 and 205.4; 68.7 and 102.9 micrograms/g (globulins). These findings indicate that Faba bean albumins and globulins form the labile and neutral nucleo-glycoprotein complexes with Cu, Mn, Fe and Zn. The process of storage and drying caused the migration of the micro and macroelements between albumins and globulins. Generally, one may say that Faba bean albumins and globulins are the source of the biologically active micro- and macroelements. PMID- 7792519 TI - [The influence of potassium sorbate addition on the quality of pickled zucchini fruit]. AB - The investigation included zucchini cultivars of Polish (Astra) and foreign (Storr's Green F1) breeding. The analysed material was harvested in the investigator's experimental field. Lactic fermentation at controlled temperature of fruits 100-130 mm in length was carried out in early September, the variants consisting of souring at the concentration of 0.05% and 0.10% in the brine which filled 35% of the volume of pickling containers. The evaluation of pickles was carried out after 6 month of souring. The raw material for pickling contained 8.67-9.66% of dry matter, 2.47-2.60% of sugars, 1.84-18.9% protein (N x 6.25), 0.42-0.50% of pectic compounds, and 46.9 mg/100 g of vitamin C. The pickles were characterized by a good organoleptic quality expressed by scores from 4.39-4.96 and by the following physico-chemical composition: dry matter 8.11-8.86%, sugars 0.9-0.11%, N x 6.25 1.54-1.56%, total acidity 0.82-1.01%, sodium chloride 2.15 2.26%, pectic compounds 0.20-0.25%, volatile acidity 43-64 mg/100, ethyl alcohol 30-35 mg/100 g, and vitamin C 10.9-14.9 mg/100 g. The addition of potassium sorbinate to the brine favourably affected the chemical composition and organoleptic quality of the final product. With the level of sorbic acid in pickles rising from 0 to 26 mg/100 g (the 0.10% addition of potassium sorbinate to the brine) the total content of acids increased by 18% and the content of preserved vitamin C by 32%, while the amount of volatile acids was reduced by 25% and that of ethyl alcohol by 38%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792520 TI - [The value of Polish field grown sweet pepper cultivars for freezing and pickling]. AB - Raw and blanched sweet pepper and frozen goods and pickles produced of blanched and non-blanched vegetable were evaluated after 6-month storage, the following cultivars of Polish origin being used in the screening: Bryza, Ino, Jantar, Kano, Kujawianka, Passat, Sono, and Zefir. The compared cultivars differed by the level of analysed indices. The variability range of dry matter content was 25%, of sugars 23%, of starch 97%, of protein 25%, of mineral constituents 24%, and of vitamin C 40%. The blanching of the raw material reduced the content of sugar by 11%, raw protein by 8%, mineral constituents by 14%, and vitamin C by 18%. The freezing and 6-month storage of frozen sweet pepper did not significantly affect its chemical composition, except vitamin C whose level was decreased by 17% on the average in the case of freezing non-blanched raw material, and by 22% when blanched sweet pepper was used. The pickling and storage of pickles significantly reduced the content of vitamin C, the losses amounting to 58% in products of non blanched and to 67% in these of blanched fruit. The lossesin protein content were relatively small while and increase in the content of dry matter, sugars, and ashy constituents was due to additives in the marinade. The process of blanching sweet pepper before freezing ensure the preservation of proper smell and taste. Hence, this treatment has to be regarded as indispensable prior to the longterm storage of frozen vegetables. In the case of pickling the blanching has no favourable effect on the organoleptic qualities. The highest organoleptic values was in pickles and frozen goods of Kujawianka, the scores being 4.5 each, however no statistical differences were found for products of Kano, Sono, Bryza, and Zefir. PMID- 7792522 TI - [Bacterial pollution with Campylobacter in surface waters of water-plants after different steps of water processing]. AB - The presence of bacteria of Campylobacter genus was investigated in 55 samples of surface water taken from Vistula river nearby Warsaw, and from different stages of water processing plants in Central and Northern water plants. For this purpose the membrane filters technique in microaerophilic conditions and differential medium with the antibiotics addition were used. Bacteria of Campylobacter genus were detected in 36% samples of surface waters and positive correlation with the contamination with coli of fecal type bacteria was found. The presence of Campylobacter was also found in water intakes in Central and Northern water plants and in water samples taken from sediment trap after fast filters and coagulation in Central water plants. No Campylobacter type bacteria were found in chlorinated water containing of free chlorine in concentration of 0.66 mg Cl2/l. PMID- 7792521 TI - [Evaluation of the current state of pollution of selected natural water resources with cadmium and lead]. AB - Concentrations of lead and cadmium in water of lakes located on agricultural and recreation areas have been analysed. Surveys were performed in summer and autumn 1988 and once more in 1993. Concentrations of both metals were analysed by atomic absorption spectrophotometry after chelation and extraction. Obtained results suggest that present concentrations of lead and cadmium are not very dangerous for analysed waters. PMID- 7792524 TI - [A comparative study of determining fluoride ions with spectrophotometric and ion selective methods]. AB - The usefulness of two methods for fluorine determination in different mineral waters was compared: a spectrophotometric method using of a zirconium-xylene reagent and electrochemical using of fluoride ion-sensitive microcapillary inset electrode. The influence of the presence of chlorine, sulphate or iron ions on the fluorine determination has been evaluated in solutions containing 0.5; 1.5; 5.0 and 10.0 mg F-/1 and increasing concentration of Cl-, SO4(2-), Fe3+ ions in the range they can occur in natural mineral waters. The ion-selective method has been found more advantageous for analysis of solutions and waters of mineralization of 5 g/l and concentrations of sulphates below 1,000 mg/l in which fluorides concentrations ranges from 0 to 1.5 mg/l. For solution of higher mineralization degree containing more than 1.5 mg F-/1 and less than 1000 mg/l of sulphates, the spectrophotometric method seems to be more advantageous. PMID- 7792523 TI - [The occurrence of keratinolytic fungi in the polluted environment of the Labedy District in Gliwice]. AB - This study was undertaken to find relationships between the degree of bacteriological contamination with qualitative composition of potentially pathogenic keratinolytic fungal population in soil, sediment and air samples from the Labedy district in Gliwice (Poland). The examined soil samples were characterized by the predominance of Botryotrichum piluliferum, Chrysosporium anamorph of Arthroderma curreyi, Myceliophthora anamorph of Ctenomyces serratus, Chrysosporium pannicola and Trichphyton ajelloi. These species are typical for keratinolytic mycoflora in moderate climate soils, and their abundance was certainly resulted from the assembly of keratin remains in the soil environment. In the light of the weak bacteriological and mycological differentiation of the examined soil samples, however, it is difficult to determine categorically the extent to which the remains were originated from sewage via soil flooding by sewage or air transportation, or from the local human and animal population. Subsequently, the population of keratinolytic fungi in sediments was found to be clearly dependent of the degree of water contamination with sewage. In badly polluted sediments, Chrysosporium pannicola, Chrysosporium anamorph of Aphanoascus fulvescens, Chrysosporium keratinophilum, Trichophyton ajelloi and Microsporum cookei were prevalent species. Keratinolytic fungi were only a small part of airborne fungal population in sewage bioaerosoles. Geomyces pannorum, a soil species better known by its celullotytic than keratinolytic properties, predominated in air samples. Some pathogenic species, such as Aspergillus flavus, Aureobasidium pullulans, Chrysporium anamorph of Aphanoascus fulvescens, Candida spp., Geotrichum candidum, Microsporum canis, Sporothrix schenckii and Trichosporon beigelii, were recovered in the present study. This confirms that the sewage-contaminated environments in an important storage place of pathogenic fungi, mostly from the opportunistic subgroup. PMID- 7792525 TI - [The influence of natural peat and isolated humic acid solution on certain indices of metabolism and of acid-base equilibrium in experimental animals]. AB - The biological effect in rats treated with natural peat homogenate and isolated humic acids has been shown in pharmacodynamic studies. After 24 days of this treatment decrease of total cholesterol, total lipids, an increase of HDL fraction of cholesterol, decrease in glucose level and increase of protein fraction of globulin, hemoglobin, hematocrit and total number of erythrocytes were observed. The treatment did not influence the electrolyte equilibrium. However, after the treatment with humic cides the respiratory acidosis not compensated with the metabolic component was observed. The activity of the natural peat was more favorable as compared to the activity of humic acids solution. PMID- 7792526 TI - [House fly development after chitin biosynthesis inhibitor application to eggs]. AB - Nine asymmetrically substituted ureas were bioassayed against house-fly (Musca domestica L.) eggs. The compounds included benzoylaryl urea derivatives, shown in Table I, (compounds 1 and 3-8) and benzoylheteroaryl ureas (2 and 9) which previously revealed effective inhibition of metamorphosis and reproduction when applied in food to the larvae and adults. The benzoyl moiety of the compounds comprise 2,6-disubstituted benzene ring with fluorine atoms (6-9), chlorine atoms (1-2) or fluorine and chlorine atoms (3-5), respectively. The majority of the compounds include aniline derivatives (1, 3-8), except the two containing pyridine ring (2) or pyridone-2 system (9). The eggs of house fly Musca domestica L. (some hours after they were laid) were put on a piece of cloth impregnated with acetone solution of tested compounds in concentrations 0.1 and 0.01%. The hatching of larvae and the later phases of development were observed. From the tested compounds one (no 8 in tab. II) decreased and delayed the hatching, two compounds (no 1 and 4 in tab. II) affected the later stages of development: the number of pupae and adults were decreased. PMID- 7792527 TI - [Evaluation of water sanitation and hygiene in swimming pools in the town of Biala Podlaska]. AB - The purpose of the study was the characteristic of physico-chemical and bacteriological features of water quality in three swimming pools of standard type accepted for most pools in the country, and it was tried to assess their sanitary-hygienic state in relation to the accepted sanitary standards. The study was carried out in the years 1991-1992 taking water samples from each pool twice in a month during water removal, and once in the whole study during pool filling. The physico-chemical and bacteriological studies were carried out by the methods evolved at the National Institute of Hygiene, and the results were compared with the obligatory standards. It was found that physico-chemical parameters of water quality different only slightly between the tested pools. Most evident differences were observed in chloride concentrations. It was noted that falling free chlorine concentration in a pool was associated with increasing bacterial contamination of water. The degree of bacterial contamination of water in that pool was above the permissible value in 18% of the studied samples. The obtained results point out water quality depends, in the first place, on correct performing of disinfection, which was not always adequate in these pools. PMID- 7792528 TI - [Coexistence of low-molecular component combustion gas formed during the burning of gaseous fuels]. AB - The equations of nitric and formaldehyde concentrations in combustion gas against carbon monoxide in combustion gas were shown in this study. Measures for various conditions of burners operating are down. It was shown that nitric oxides concentration in combustion gas is proportional to carbon monoxide concentration and universally proportional to fuel consumption velocity and dry product volume of combustion gas formed from fuel elementary volume. In case of formaldehyde all three partial relationships were inversely proportional. PMID- 7792529 TI - [Mechanisms of bone loss in osteoporosis]. AB - Aging and menopause are the two main determinants of osteoporosis, a rarifying osteopathy due to bone loss. Type I osteoporosis observed in post-menopausal women is characterized mainly by trabecular bone loss results from an unbalanced coupling between resorption and formation inducing a thinning of trabeculae and from an increased osteoclast activation resulting in irreversible trabecular perforation. Anti-osteoclastic drugs prevent trabecular and cortical bone loss. Drugs that stimulate osteoblastic proliferation thicken trabecular plates but do not restore the normal trabecular microarchitecture after complete destruction of a large number of trabeculae. In type II osteoporosis, cortical bone loss is favoured by secondary hyperparathyroidism and is responsible for hip fracture. Calcium and vitamin D supplementations decrease the risk of hip fractures by reducing the secondary hyperparathyroidism. PMID- 7792530 TI - [Present and future epidemiology of osteoporosis]. AB - Osteoporotic patients are exposed to fractures at all bones sites, mainly the upper extremity of the femur, the vertebral bodies, and the distal forearm. According to an overview of 6 French surveys, it is estimated that there has been, in 1990, 45,000 to 50,000 new fractures of the upper extremity of the femur, in patients aged 20 years and above. Owing population aging, more than 145,000 fractures are expected to occur in 2050. The frequency of osteoporosis, its spontaneous tendency to increasing prevalence, its functional consequences and its cost make it a major public health issue with a requirement for a specific preventive strategy. PMID- 7792532 TI - [Clinical usefulness of biochemical markers of bone remodeling in osteoporosis]. AB - Osteoporosis with its various clinical expressions is characterized by abnormalities of bone remodeling that can be assessed by biochemical markers of formation and resorption. Measurements of the serum concentration of osteocalcin and bone alkaline phosphatase (formation) and of the urinary excretion of pyridinoline and its peptides (resorption) are the most efficient markers in the investigation of osteoporosis. Recent studies, some of them still in progress, allow to define the clinical use of these markers: firstly to improve the evaluation of the fracture risk, and secondly to monitor the efficacy of antiresorptive drugs. PMID- 7792533 TI - [Risk factors and prevention of postmenopausal osteoporosis]. AB - Preventing postmenopausal bone loss and osteoporotic fractures (vertebral crush fractures and femoral neck fractures) is an important challenge for the next decades. This goal should be achieved by developing screening strategies and deploying established preventive measures. The risk assessment is currently based on densitometric measurements of bone mass and knowledge of risk factors for low bone mass and/or exaggerated bone loss. Hormone replacement therapy is the only well established treatment for preventing osteoporotic fractures. Therefore, it should be recommended to many women. It is important to associate a progesterone derivative with the oestrogen, to exclude patients with breast cancer history and to ensure a follow up by a gynaecologist. Alternative regimens could be useful in patients with low acceptance or contraindication to oestrogens. The long term antifracture efficacy of these molecules remains to be determined, and they have yet, at least in France, no marketing authorization for this purpose. PMID- 7792531 TI - [Contribution of osteo-densitometry in the definition and diagnosis of osteoporosis]. AB - Since its first characterisation, osteoporosis has always been defined on an anatomical basis. The term osteoporosis refers to a reduction (or atrophy) in the amount of bone tissue and to microarchitectural deterioration without any mineralisation defect. Its clinical significance lies in the fractures (vertebral fracture, Colles' fracture and hip fracture) that occur spontaneously or after a minimal trauma. During the past 15 years, developments in technology of bone mass measurement (osteodensitometry) currently allow a diagnosis of osteoporosis at its anatomical stage characterised by a reduction in bone mass (osteopenia) without any symptom. A definition based on densitometry offers the major advantage of an early diagnosis, well before the development of fractures. It has been validated recently by several prospective studies which have confirmed the close relationship between the decrease in bone mass and the fracture risk. This modern densitometric approach of osteoporosis has major therapeutic implications. Indications of curative treatments of osteoporosis has major therapeutic implications. Indications of curative treatments of osteoporosis should be reconsidered according to the contribution of bone densitometry. PMID- 7792534 TI - [Diagnosis and treatment of osteoporotic vertebral collapses]. AB - Vertebral fracture is a typical and frequent complication of trabecular osteoporosis. It is responsible for pain and disability. Diagnosis is supported by X-rays and some pitfalls must be known and avoided. Physical treatment is important in order to prevent recurrence. Among different treatments available in osteoporosis, ostrogenotherapy must be discussed, even after fractures have occurred. PMID- 7792535 TI - [Physiopathology and prevention of fractures of the proximal end of the femur]. AB - Hip fracture is the most important skeletal problem in elderly people. Its two main determinants are falls and bone loss leading to an intrinsic bone fragility. Bone fragility results from postmenopausal and senile bone loss. The latter is increased by the secondary hyperparathyroidism of elderly persons which is induced by a combination of vitamin D deficiency and calcium intake, both very common in old age, particularly in Europe. Prophylactic strategies should be based on prevention of falls and of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal oestrogen replacement therapy and a late prevention of senile secondary hyperparathyroidism by vitamin D and calcium supplements which have recently been shown to reduce by 25% the number of hip fractures in a prospective study performed in a large population of institutionalized women. Therefore, it is never too early to pay attention to the risk of osteoporosis, and never too late to prevent hip fractures. PMID- 7792536 TI - [Secondary osteoporosis]. AB - Although primary osteoporosis is much more frequent than other diseases associated with osteopenia, the diagnosis of idiopathic osteoporosis should be made only after the causes of secondary osteoporosis have been excluded. Indeed, therapeutic efficiency in secondary osteoporosis depends mainly on the concomitant treatment of the actual cause of osteopenia. Glucocorticoid-induced osteoporosis is the commonest form of secondary osteoporosis, mainly for doses of prednisone of 0.1 mg/kg/day or greater. Hypogonadism in men and women, idiopathic hypercalciuria and chronic alcoholism in men are other frequent causes of osteopenia. The diagnosis of secondary osteoporosis is based on careful examination as well as biochemical and hormonal investigations. Together with the treatment of the associated disease, correction of other risk factors, calcium supplementation, and a regular program of weight-bearing physical activity may be of benefit to reduce bone loss. As fluoride is able to stimulate bone formation, it is an effective agent in the treatment of glucocorticoid or alcohol-induced osteoporosis. PMID- 7792537 TI - [Infant mortality and morbidity. Definitions, main causes related to age. Obligatory health examinations]. PMID- 7792538 TI - [Drug accidents of immunological origin. Physiopathology]. PMID- 7792539 TI - [Salivary lithiasis. Diagnosis, principles of treatment]. PMID- 7792540 TI - [Methods of evaluating nutritional status]. PMID- 7792541 TI - [Chronic kidney failure. Etiology, physiopathology, diagnosis, treatment]. PMID- 7792542 TI - [Mitral valve stenosis]. PMID- 7792543 TI - [Burns. Etiology, physiopathology, diagnosis, early treatment]. PMID- 7792544 TI - [Cutaneous ectoparasitosis: pediculosis. Epidemiology, diagnosis, treatment]. PMID- 7792545 TI - Physical and psychological workload in men with and without low back pain. AB - Current and retrospective physical and psychological workload was studied in 148 mean, 45-55 years old. The men represented three groups with respect to low back health status: Healthy low back (Group 1, n = 36), intermittent low back pain (LBP) (Group 2, n = 91) and chronic LBP (Group 3, n = 21). The methods used were a self administered questionnaire, a rating scale of perceived exertion, and blind expert assessment built on a classification of job titles. Group 1, the back-healthy subjects, had been less exposed to heavy physical work than subjects with intermittent LBP (Group 2) and chronic LBP subjects (Group 3) through their whole working-career and in their present work (p < or = 0.05, p < or = 0.01). Group 2 tended to be significantly less exposed in their present work than Group 3 (p < or = 0.06). Non-neutral working postures were reported more often in Groups 2 and 3 than in Group 1 (p < or = 0.05, p < or = 0.001). Both groups 2 and 3 perceived present and earlier work to be more strenuous than Group 1, with respect to the low back (p < or = 0.000). Subjects in the healthy low-back group had lower values in the qualitative demand index ("too difficult working tasks" and "too great responsibility") than subjects in Groups 2 and 3 (p < or = 0.01). This study indicates that more attention should be given to the individual's perception of physical workload. PMID- 7792547 TI - The Balance Scale: reliability assessment with elderly residents and patients with an acute stroke. AB - The objective of this study was to assess the reliability of the Balance Scale. Subjects were chosen from a larger group of 113 elderly residents and 70 stroke patients participating in a psychometric study. Elderly residents were examined at baseline, and at 3, 6 and 9 months, and the stroke patients were evaluated at 2, 4, 6 and 12 weeks post onset. The Cronbach's alphas at each evaluation were greater than 0.83 and 0.97 for the elderly residents and stroke patients respectively, showing strong internal consistency. To assess inter-rater reliability, therapists treating 35 stroke patients were asked to administer the Balance Scale within 24 hours of the independent evaluator. Similarly, caregivers at the Residence were asked to test the elderly residents within one week of the independent evaluator. To assess intra-rater reliability, 18 residents and 6 stroke patients were assessed one week apart by the same rater. The agreement between raters was excellent (ICC = 0.98) as was the consistency within the same rater at two points in time (ICC = 0.97). The results support the use of the Balance Scale in these groups. PMID- 7792548 TI - Gait analysis of hemiplegic patients by measurement of ground reaction force. AB - Ground reaction force during walking was measured and analyzed in 58 patients who had been hemiplegic for more than 6 months. Utilizing the impulse (area between a component curve and the baseline) as an assessment value, several parameters were selected to represent the characteristics of each component curve (vertical, fore aft and lateral) of the ground reaction force, and correlated with the degree of motor recovery in the patients. As a result, a high correlation was found between these parameters and the degree of motor recovery, indicating that ground reaction force well reflects the degree of motor recovery, which is highly correlated with the gait ability of hemiplegic patients. This evaluation method would also be very helpful for objective and quantitative estimation of the gait of hemiplegic patients. PMID- 7792546 TI - The role of the psychologist in multidisciplinary treatments for chronic neck and shoulder pain: a controlled cost-effectiveness study. AB - This study was designed to determine a cost-effective use of psychologist resources in multimodal cognitive-behavioural treatments (MMCBT) for chronic neck/shoulder pain. A randomised controlled trial was conducted with 66 patients divided in two groups. The first group (A) was treated following the approach of MMCBT with the clinical psychologist only functioning as a "coach" to the other health professionals. In this group, the psychologist had on average 5 hours of input per patients. The second group (B) was treated with the same inpatient MMCBT but with the behavioural component administered by the clinical psychologist directly to the patients. In this second group the psychologist had on average 17 hours of input per patient in the entire intervention. The outcome variables included physical, emotional and social factors, and sick-leave. Both groups showed significant improvements over time. The improvements were evident only in sub-groups, specifically in women. The only significant difference between the groups was in "perceived helplessness" favouring the "psychologist contact" setting. It is concluded that in terms of input of clinical psychology, the treatment setting with the "coaching" technique proved to be the most cost effective use of the psychologist in the two treatment settings investigated. PMID- 7792550 TI - Does hyperextension have an unloading effect on the intervertebral disc? AB - A stadiometer (a device to measure the overall height of a subject) was used to determine the effect of hyperextension in rehydration of the intervertebral disc. Hyperextension for 20 minutes in a prone posture was compared with the prone posture alone for 20 minutes. The stadiometer measurement was made after the subject was exposed to 10 kg of loading applied to the shoulders for five minutes and after each of the recovery postures. It was found that hyperextension gave a significantly increased height recovery compared with the prone posture. PMID- 7792549 TI - Intervention design for rehabilitation at home after stroke. A pilot feasibility study. AB - This study aimed at identifying the characteristics and feasibility of rehabilitation at home for acute stroke patients in south-west Stockholm. A population-based systematic sample of 16 patients, fulfilling defined criteria, was selected from approximately 1/3 of the stroke patients having been in hospital for one week or more at a neurology department, and offered early discharge in combination with home-based rehabilitation as an alternative to sustained rehabilitation in hospital. Fifteen patients, mean age 68.2 years, male/female ratio 9/6, independent in feeding and continent one week after acute stroke, participated in the study. The most important components of the home based rehabilitation programme were that: 1) one therapist was selected as case manager using the other therapists on a consultant basis; 2) the training sessions consisted of different task-specific activities, based on the patients' personal interest; 3) education and individual counselling were offered to all spouses; and 4) adherence to structured training between therapy sessions was promoted. The length of such programmes varied from 4 to 19 weeks after discharge and the mean number of home visits was 11. Reported time for training between therapy sessions for 14 patients was mean 1.2 hours per day. The patients' lifestyle activities, personal and instrumental ADL, and motor capacity at 3, 6 and 12 months after stroke, assessed by validated and reliable methods, followed patterns similar to those reported for other stroke patients. The mean time in hospital for patients in the study was 14 days; for patients with similar ADL capacity but not included in the study it was 27 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792551 TI - Metabolic response and muscle glycogen depletion pattern during prolonged electrically induced dynamic exercise in man. AB - Muscle glycogen depletion pattern and metabolic responses during voluntary (VOL) and functional electrical stimulated (FES) dynamic knee-extensor exercise with one leg were evaluated. Seven healthy men exercised for 60 minutes at 30 W with an pulmonary oxygen uptake of 0.8 and 1.01 min-1, and respiratory exchange ratios of 0.90 and 0.95 in VOL and FES, respectively. Heart rate reached a level around 90 beats min-1 (VOL) and up to 110 beats min-1 (FES). Muscle glycogen decreased in FES with 260 and 290 mmol kg-1 d.w. in vastus lateralis and m. rectus femoris, respectively, compared with 45 and 160 mmol kg-1 d.w. in VOL (p < 0.05). In FES the percentage of empty and almost empty fibres determined by periodic acid Schiff staining in vastus lateralis and rectus femoris was 50 and 77% of type I, 63 and 90% of type IIa, and 59 and 84% of type IIb fibres, respectively, whereas in VOL it was 24 and 26% of type I, 7 and 19% of type IIa, and 2 and 3% of type IIb fibres. Muscle lactate reached 30 mmol kg-1 d.w. in FES and was 9 mmol kg-1 d.w. lower in VOL. The changes in blood lactate and NH3 during the exercise were slightly higher in FES than in VOL, whereas the alterations in glucose, FFA, and K+ were small in both exercise modes. The pressure in the two muscle portions at different locations (proximal-distal) and depths was always higher (approximately 50%) in FES than in VOL, reaching levels around 55 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792552 TI - Deterioration of motor function in myotonic dystrophy and hereditary motor and sensory neuropathy. AB - In order to obtain more information about the deterioration of motor function in patients with myotonic dystrophy and in patients with hereditary motor and sensory neuropathy, changes in strength and functionality were determined at one year intervals, over a follow-up period of 1 to 5 years. Twenty-five myotonic dystrophy patients and 16 hereditary motor and sensory neuropathy patients participated. Strength measurements were restricted to knee extension and flexion torques measured isokinetically on a dynamometer at two velocities (120 and 60 degrees/s). Functionality was measured as scaled time scores for rising from sitting, rising from supine, walking and stair climbing. Myotonic dystrophy patients showed a reduction of knee extension torques at 60 degrees/sec (mean decrease per year 5.7 Nm, or 9%) as well as a decrease in functionality. Hereditary motor and sensory neuropathy patients showed no statistically significant changes in torques or functionality. The correlation between isokinetically measured knee extension torques and functional scores was statistically significant in myotonic dystrophy but not in hereditary motor and sensory neuropathy. No correlation was found between changes in torques and changes in functional scores. PMID- 7792554 TI - Conjoined double internal mammary artery grafting. AB - Double internal mammary artery (IMA) grafting to the coronary arteries was performed on 82 patients. In ten of them one IMA was used as a free graft, and was proximally connected to the other ("conjoined" double IMA), the indications being insufficient supply of adequate veins, diseased aortic wall, availability of only a short right IMA segment for free grafting, occluded left subclavian artery, and when distal and scattered lesions of relatively important vessels had to be bypassed. Additional sequential IMA anastomoses were performed in four patients and an additional sequential vein graft in a fifth. All patients became angina-free postoperatively and have remained so during observation up to 16 months. Recatheterization studies were performed in six patients and in all of them the IMA-to-IMA (n = 6) and distal anastomoses (n = 26) were patent. Conjoined double IMA grafting is an important option available to the cardiac surgeon for management of selected patients with coronary artery disease. PMID- 7792553 TI - Traumatic inferior vena caval injuries. AB - Twenty-three cases of inferior vena caval injury (1.4% of all operatively managed abdominal injuries) are reviewed. The caval injury presented as free haemorrhage in 15 cases and as a retroperitoneal haematoma in eight. The site of vena caval injury was at or above the level of the renal veins in 14 cases (61%). Successful lateral suture repair was achieved in 18 cases (78%). The overall mortality rate was 39%. Factors positively associated with survival were stab wound, presentation as retroperitoneal haematoma, infrarenal injury, low Abdominal Trauma Index score and small peroperative blood loss. Concomitant injury to the abdominal aorta, liver or kidney worsened the prognosis. The crucial factor in management of inferior vena caval injuries is rapid and effective control of bleeding, whether from the caval or associated injuries. PMID- 7792555 TI - Mitral valve prosthetic implantation with preservation of native mitral valve apparatus. AB - To avoid postoperative morbidity and mortality often associated with left ventricular dysfunction after mitral valve replacement (MVR) for chronic mitral insufficiency, reconstruction or preservation of the native mitral valve apparatus may be attempted during mitral prosthetic implantation (MPI). The effects of mitral surgery on heart function, studied with echocardiography and radionuclide angiography, were compared in seven patients with MPI (study group) and five with MVR (control group) who underwent complete preoperative, early postoperative and 3-6 months follow-up examinations. Preoperatively there was significant intergroup difference only in right ventricular ejection fraction measured at radionuclide angiography, which was lower in the MPI group (p < 0.05). At follow-up the MPI group had improved as regards this fraction (p < 0.005) and stroke volume index (p < 0.05). The number of patients with improved NYHA class at follow-up was significantly greater in the MPI group. Our preliminary experience with preservation of the native mitral valve apparatus thus suggests that the method offers haemodynamic advantages for postoperative right ventricular function. PMID- 7792556 TI - CarboMedics valve in congenital heart disease. Midterm follow-up study of 14 patients. AB - In 14 patients aged 5-329 (mean 131) months a CarboMedics valve was implanted because of congenital heart disease. The preoperative NYHA function class was III IV in ten cases. Seven aortic and seven atrioventricular valves were replaced without early mortality. All patients were followed up, with mean observation time 27 months (total 384 months). One of the 14 patients died of heart failure 10 months postoperatively. Thrombosis occurred in four valves, three in tricuspid and one in mitral position. In all patients who received only warfarin, anticoagulation was demonstrably inadequate. Consequently we now recommend antiplatelet medication in addition to warfarin for children with atrioventricular mechanical valve replacement. In our experience the complication rate with CarboMedics prosthesis is acceptable, provided that anticoagulant therapy is adequate. PMID- 7792557 TI - Microvascular injury induced by intravascular platelet aggregation. An experimental study. AB - Microvascular injury due to platelet aggregation was studied in cats for an hour after 1-hour intraaortic infusion of a suspension of collagen fibrils. Haematocrit and numbers of circulating platelets and leukocytes were repeatedly measured in arterial blood and a major cutaneous lymph vessel in the thigh was cannulated for measurement of lymph flow and erythrocyte counts in peripheral lymph. There were seven groups, each of eight cats, viz. normal cats infused with collagen (I) or vehicle (II) and collagen-infused cats which were platelet depleted--by antiserum (III), or neutrophil-depleted--by anti-serum (IV), or decomplemented--by cobra venom (V), or pretreated with indomethacin--10 mg/kg (VI), or treated with nonimmunized serum (VII). Induced intravascular platelet aggregation reduced the numbers of circulating platelets and leukocytes, and increased haematocrit, lymph flow and numbers of red cells in peripheral lymph. These effects were inhibited by platelet depletion and indomethacin and attenuated by decomplementation and neutrophil depletion. Platelet aggregation was thus shown to induce microvascular injury and increase microvascular permeability, which is partly dependent on complement and neutrophils. PMID- 7792558 TI - Myocardial metabolism 8 hours after coronary surgery: effects of dopamine. AB - Myocardial substrate metabolism is abnormal in the early period after cardiac surgery. Myocardial uptake of substrates remains restricted 6 hours postoperatively and cannot match the demand during periods of increased energy requirements. We investigated the relationship between myocardial oxidative rate and substrate uptake in 22 men c. 8 hours after coronary surgery. Myocardial energy demand was raised experimentally by infusing dopamine. The influence of selective beta 1-blockade was analyzed. The uptake of free fatty acids dominated (34.74 +/- 8.83 mmol/min*10(-3) and sufficed to explain the oxygen consumption in basal postoperative conditions (0.468 +/- 0.051 mumol/min) and during amplified energy requirements (0.881 +/- 0.117, r = 0.71). Although the capacity to adjust substrate uptake to energy requirements thus was regained, the uptake of glucose and of lactate (6.14 +/- 13.13 and 2.29 +/- 20.31 mmol/min*10(3) respectively) was marginal, which may be important for ischaemic tolerance. Metoprolol influenced oxygen consumption during amplified adrenergic activity, but did not markedly affect substrates. PMID- 7792559 TI - Ceftriaxone vs cefuroxime for infection prophylaxis in coronary bypass surgery. AB - The most serious infection after coronary artery bypass grafting (CABG) is mediastinitis following deep sternal wound infection. Antibiotic prophylaxis for at least 48 hours has been recommended. In this trial 551 consecutive patients were randomized to receive ceftriaxone in a single dose or cefuroxime thrice daily until the end of the second postoperative day. The overall infection rate was 7.7% in the ceftriaxone and 8.3% in the cefuroxime group, and the incidence of deep sternal infection was 2.9% in both groups. Significant risk factors for such infection were chronic respiratory disease (p < 0.001) and diabetes (p < 0.01). The antibiotic prophylaxis had no harmful effects on the colonic flora in either group. Acquisition and delivery costs for the prophylactic agents were three times higher in the cefuroxime than in the ceftriaxone group. Both antibiotics are concluded to be equally safe and effective. Single-dose ceftriaxone prophylaxis is as effective as cefuroxime given for 48 hours postoperatively. Single-dose ceftriaxone is also simple to use. PMID- 7792560 TI - Lung cancer containing growth hormone-releasing hormone associated with hypertrophic osteoarthropathy. Case report. AB - In a 49-year-old man, large-cell carcinoma of the lung was accompanied by raised serum levels of growth hormone (GH) and growth hormone-releasing hormone (GHRH) and hypertrophic osteoarthropathy. Immunohistochemically the tumour contained GHRH but not GH. The osteoarthropathy disappeared after resection of the primary tumour and did not reappear after its recurrence. The high serum GH level presumably was due to ectopic GHRH production in the tumour. The hypertrophic osteoarthropathy was not clearly attributable to these hormones. PMID- 7792561 TI - Tracheobronchomegaly accompanied by bilateral giant pulmonary bullae and left spontaneous pneumothorax. Case report. AB - A 58-year-old man with tracheobronchomegaly underwent simultaneous bilateral pulmonary surgery via median sternotomy for left spontaneous pneumothorax with bilateral giant bullae. Postoperative hypoxaemia and pneumonia necessitated ventilator and antibiotic treatment. Simultaneous bilateral pulmonary operations in patients with tracheobronchomegaly carry a risk of respiratory complications. PMID- 7792562 TI - Clinical significance of intranodal and extranodal growth in lymph node metastases of non-small cell lung cancer. AB - In non-small cell lung cancer with mediastinal lymph node metastasis, intranodal growth is regarded as prognostically more favourable than extranodal growth. We evaluated the clinical implications. Mediastinal lymph node metastases removed at mediastinoscopy and/or surgery were classified as intranodal, extranodal or indefinite. "Minimal N2 disease" denoted a solitary, intranodal metastasis, "extranodal" at least one extranodal lymph node metastasis, and "indefinite" more than one intranodal or at least one indefinite metastasis. Although in patients with resected N2 disease, c. 21% of the nodal metastases were "indefinite", survival was significantly better in minimal N2 disease than in the combined groups with extranodal and indefinite lymph node metastases. Of the metastatic nodes removed at mediastinoscopy, 75% were unsuitable for definite classification as only intranodal or extranodal. Only 1 of 49 patients had purely intranodal N2 disease. Thus, it was seldom feasible to classify mediastinoscopic lymph node involvement as intranodal or extranodal, and this classification is unhelpful as regards decisions on thoracotomy. However, when nodal involvement in resected N2 disease was limited to a single node with intranodal growth, the prognosis was better than in patients with extranodal disease or more than one intranodal metastasis or indefinite nodes. PMID- 7792564 TI - Swiss Society of Internal Medicine, Hematology, Hypertension, Clinical Chemistry, Endocrinology, Nephrology, Clinical Pharmacology. Montreux, 18-20 May, 1995. Abstracts. PMID- 7792563 TI - Fifty years of cardiac and pulmonary surgery 1942-1993. The beginning of open heart surgery of postoperative intensive care. The first complete left heart catheterization. Mechanical heart valves. PMID- 7792565 TI - Outcome of a clinical cohort of unipolar, bipolar and schizoaffective patients. Results of a prospective study from 1959 to 1985. AB - In a prospective study, 186 unipolar depressives and 220 cases of bipolar disorder meeting DSM-III criteria for major depression or mania were followed up. Subjects were classified according to polarity and the presence or absence of schizophrenic symptoms, into four diagnostic subgroups: unipolar depression, bipolar disorder, unipolar schizoaffective disorder and bipolar schizoaffective disorder. At the last follow-up in 1985, 53% of the patients had deceased. Eleven percent of the sample (17% of all deaths) had committed suicide. The risk of suicide was associated with clinical severity and onset prior to the age of 60. However, there was no difference in suicide rates according to sex or diagnostic subgroup. Late onset of affective illness was associated with chronicity, which occurred in 10 to 19% of cases. Recovery was more frequent among unipolar than among bipolar patients. The 5-year remission rates (i.e. 26% in unipolars, 16% in bipolars) were independent of the number of episodes. PMID- 7792566 TI - [Status of the discussion regarding cost-effectiveness of community psychiatry and inpatient psychiatry]. AB - In the current climate of escalating health care costs and shrinking resources, higher priority is also being given to the relation between costs and benefits of reform efforts and further developments of existing service delivery systems in the field of mental health. Some proponents of community psychiatry have predicted in a pointed manner that a change in the allocation of resources in favor of community-based care would dramatically decrease the need for hospital beds, cost half as much and be clinically at least as efficacious as inpatient treatment. The author gives careful consideration to these postulates based on today's available literature and on his own experiences in Mannheim and in Bern. He presents an array of newer findings which places them in perspective and to some extent contradicts them as well. Recent studies on the effects of an expansion of outpatient treatment programs on the overall mental health delivery system suggest that in areas with already reasonably developed community services its further enhancement rarely has an effect on the number of admissions to and length of hospital stays. In addition, the postulate that community care is considerably less costly only holds if in- and outpatient facilities are not considered to be integral parts of a comprehensive system of mental health care which both serve different purposes. Accordingly, the question of the effectiveness of treatment must also be discussed very distinctively. Although a network of well-functioning community-based services is (not yet) a veritable alternative, it can by all means, however, serve as a useful counterpart to the intensive treatment offered in modern mental institutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792567 TI - [Effectiveness of psychiatric day clinic treatment. An empirical study from the psychiatric service of the Thun regional hospital]. AB - As a part of a new community mental health service in a non-university region this intermediary institution questioned its effectiveness. We wanted to know whether rehabilitative goals were attained at all and whether achieved changes would persist a certain time beyond discharge. With the use of goal attainment scaling changes in relation to goals defined in the beginning of the treatment were rated at the end of it and again one year after discharge. The psychologist who took care of these 46 catamnestic interviews had not been personally involved in the treatment. The positive results regarding "job situation" and "social contacts" as well as the immutability of "lodging situation" and the incapacity to keep up with the realization of "spare time interests" after discharge are discussed. The reflections are made within the frame of different levels of evaluation. PMID- 7792569 TI - President's message: creating your own challenges. PMID- 7792570 TI - The pharmacotherapy of spinal spasticity: a decade of progress I. Theoretical aspects. PMID- 7792568 TI - Course of a clinical cohort of unipolar, bipolar and schizoaffective patients. Results of a prospective study from 1959 to 1985. AB - This paper reports the results of a 27 year prospective study of 186 unipolar depressives and 220 bipolar disorders meeting DSM-III criteria for major depression or mania. Subjects were classified into four diagnostic subgroups, according to polarity and presence or absence of schizophrenic symptoms: unipolar depression, bipolar disorder, unipolar schizoaffective disorder and bipolar schizoaffective disorder. Course parameters were assessed for all samples. As the sequence of subtypes of affective and schizoaffective disorders progresses from unipolar depression, schizodepression, pure affective bipolar disorder to schizobipolar disorder, a systematic decrease in age of onset and length of episode can be observed. When compared to unipolar disorders (unipolar depression and schizodepressive disorder), bipolar (bipolar and schizobipolar) disorders showed more periodicity, characterized by greater number of total episodes, more episodes per year, but with shorter episodes and cycles. Despite the lower age of onset among schizoaffective subjects compared to pure affective disorders, the only difference in course between the two groups was a greater frequency in episodes requiring hospitalization among schizoaffectives. PMID- 7792571 TI - Nursing case management: enhancing interdisciplinary care of the spinal cord injured patient. AB - Comprehensive care of the person with a spinal cord injury (SCI) requires collaborative, coordinated, interdisciplinary care. It is imperative that the care provided by nurses, therapists, physicians, and ancillary personnel is organized and integrated in a holistic manner if optimal outcomes of rehabilitation are to be achieved. Nursing case management has been identified as an approach to health care delivery that provides quality, patient-centered care. The potential impact of this care delivery model on the health care system for persons with SCI includes quality rehabilitation outcomes, increased patient satisfaction, enhanced interdisciplinary relationships, and improved continuity of care from intensive care to community settings. PMID- 7792572 TI - Development and testing of computer software for nursing assessment and care planning at a spinal cord injury center. AB - This paper describes a pilot project using a Macintosh personal computer and customized software to computerize nursing admission assessment and care planning data. The project setting is a 47-bed Spinal Cord Injury Center with two inpatient units and an outpatient department serving approximately 1,000 patients with spinal cord injury at a Department of Veterans Affairs Medical Center in northern California. The computer software development, implementation, and evaluation are described. This software (MacNursing) was found to be a low cost, customized approach to computerizing spinal cord injury admission assessment data and care planning which reduces repetitive writing and facilitates continuity of care. Personal computers and this software have provided the mechanism for establishing a spinal cord injury patient database. PMID- 7792573 TI - Reliability, validity and data collection. PMID- 7792574 TI - How do you define "nurse"? PMID- 7792575 TI - President's message: national networking. PMID- 7792576 TI - Catheter cleaning for re-use in intermittent catheterization: new light on an old problem. AB - Clean intermittent catheterization is a common method of urinary elimination for people with Spinal Cord Injuries. The methods of catheter cleaning for re-use, however, have not been validated with research studies. This study compared the effectiveness of Hydrogen Peroxide, vinegar, dishwashing detergent, and tap water alone to clean catheters contaminated with Pseudomonas aeruginosa and Escherichia coli. The effect of rinsing and drying before cleaning was also examined, as well as the effect of storage in paper or plastic bags after cleaning. Results indicated that rinsing and drying catheters immediately after use was the most effective at reducing bacteria to very near zero. Elements of a procedure are outlined, as well as plans for further development and testing of a rinse & dry procedure for catheter cleaning and re-use. PMID- 7792577 TI - Finding success in research? The first step: literature search! PMID- 7792579 TI - What is non-compliance and how do I handle it? PMID- 7792578 TI - The pharmacotherapy of spinal spasticity: a decade of progress. II. Therapeutics. AB - Spinal spasticity is the term used to describe the increase in muscle tone which often develops following spinal cord injury (SCI). A review of spasticity and approaches to its treatment has been presented in a previous article. The purpose of this paper is to discuss the pharmacologic agents that are currently used to treat spinal spasticity. These medications can be classified as centrally and peripherally acting agents. The following review is therefore organized into two sections, according to the site of drug action. PMID- 7792580 TI - Bowel care: implementing changes toward quality improvement. AB - This article describes the challenges accepted by two healthcare teams at the Hampton Veterans Affairs Medical Center, which impacted significantly upon the practice of nursing. The first healthcare team developed a medium size glycerine suppository ("glycerine bomb"), which was determined to be more effective than the bisacodyl in oil base suppository. The second team evaluated the effectiveness of a suppository of choice ("Magic Bullet") which was approved for use and replaced the "glycerine bomb." The need for a formalized protocol for a bowel care program was identified, developed and implemented. A bowel care program quality improvement monitor was developed to evaluate the effectiveness of the protocol. With continuous monitoring, we are challenged to evaluate our findings and restructure our interventions. PMID- 7792581 TI - Scientific conduct: contrasts on a gray scale. PMID- 7792582 TI - An active National Institute of Mental Health. PMID- 7792585 TI - Play ball! PMID- 7792584 TI - Play ball! PMID- 7792586 TI - Key NASA lab under fire for animal care practices. PMID- 7792583 TI - Play ball! PMID- 7792587 TI - U.K. Health Care. Will research be priced out of the market? PMID- 7792588 TI - Remapping the motor cortex. PMID- 7792589 TI - Discovery of AT gene sparks biomedical research bonanza. PMID- 7792590 TI - Indiana: wrong answers--but no right ones. PMID- 7792591 TI - Pittsburgh: interwoven with the fabric of learning. PMID- 7792592 TI - Stanford: bringing in the big guns. PMID- 7792593 TI - Dispute slows paper on "remarkable" vaccine. PMID- 7792594 TI - Share and share alike isn't always the rule in science. PMID- 7792595 TI - IIT: serving up ethics for lunch. PMID- 7792596 TI - How the brain creates imagery: projection to primary visual cortex. PMID- 7792597 TI - Crystal structure of lac repressor core tetramer and its implications for DNA looping. AB - The crystal structure of the tryptic core fragment of the lac repressor of Escherichia coli (LacR) complexed with the inducer isopropyl-beta-D thiogalactoside was determined at 2.6 A resolution. The quaternary structure consists of two dyad-symmetric dimers that are nearly parallel to each other. This structure places all four DNA binding domains of intact LacR on the same side of the tetramer, and results in a deep, V-shaped cleft between the two dimers. Each monomer contributes a carboxyl-terminal helix to an antiparallel four-helix bundle that functions as a tetramerization domain. Some of the side chains whose mutation reduce DNA binding form clusters on a surface near the amino terminus. Placing the structure of the DNA binding domain complexed with operator previously determined by nuclear magnetic resonance onto this surface results in two operators being adjacent and nearly parallel to each other. Structural considerations suggest that the two dimers of LacR may flexibly alter their relative orientation in order to bind to the known varied spacings between two operators. PMID- 7792598 TI - Electron tunneling in proteins: coupling through a beta strand. AB - Electron coupling through a beta strand has been investigated by measurement of the intramolecular electron-transfer (ET) rates in ruthenium-modified derivatives of the beta barrel blue copper protein Pseudomonas aeruginosa azurin. Surface histidines, introduced on the methionine-121 beta strand by mutagenesis, were modified with a Ru(2,2'-bipyridine)2(imidazole)2+ complex. The Cu+ to Ru3+ rate constants yielded a distance-decay constant of 1.1 per angstrom, a value close to the distance-decay constant of 1.0 per angstrom predicted for electron tunneling through an idealized beta strand. Activationless ET rate constants in combination with a tunneling-pathway analysis of the structures of azurin and cytochrome c confirm that there is a generally efficient network for coupling the internal (native) redox center to the surface of both proteins. PMID- 7792599 TI - ILR1, an amidohydrolase that releases active indole-3-acetic acid from conjugates. AB - In plants, the growth regulator indole-3-acetic acid (IAA) is found both free and conjugated to a variety of amino acids, peptides, and carbohydrates. IAA conjugated to leucine has effects in Arabidopsis thaliana similar to those of free IAA. The ilr1 mutant is insensitive to exogenous IAA-Leu and was used to positionally clone the Arabidopsis ILR1 gene. ILR1 encodes a 48-kilodalton protein that cleaves IAA-amino acid conjugates in vitro and is homologous to bacterial amidohydrolase enzymes. DNA sequences similar to that of ILR1 are found in other plant species. PMID- 7792600 TI - A single ataxia telangiectasia gene with a product similar to PI-3 kinase. AB - A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer. PMID- 7792601 TI - Crystal structure of Pseudomonas mevalonii HMG-CoA reductase at 3.0 angstrom resolution. AB - The rate-limiting step in cholesterol biosynthesis in mammals is catalyzed by 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a four-electron oxidoreductase that converts HMG-CoA to mevalonate. The crystal structure of HMG CoA reductase from Pseudomonas mevalonii was determined at 3.0 angstrom resolution by multiple isomorphous replacement. The structure reveals a tightly bound dimer that brings together at the subunit interface the conserved residues implicated in substrate binding and catalysis. These dimers are packed about a threefold crystallographic axis, forming a hexamer with 23 point group symmetry. Difference Fourier studies reveal the binding sites for the substrates HMG-CoA and reduced or oxidized nicotinamide adenine dinucleotide [NAD(H)] and demonstrate that the active sites are at the dimer interfaces. The HMG-CoA is bound by a domain with an unusual fold, consisting of a central alpha helix surrounded by a triangular set of walls of beta sheets and alpha helices. The NAD(H) is bound by a domain characterized by an antiparallel beta structure that defines a class of dinucleotide-binding domains. PMID- 7792603 TI - Transcriptional activation by tetracyclines in mammalian cells. AB - A transcriptional transactivator was developed that fuses the VP16 activation domain with a mutant Tet repressor from Escherichia coli. This transactivator requires certain tetracycline (Tc) derivatives for specific DNA binding. Thus, addition of doxycycline to HeLa cells that constitutively synthesized the transactivator and that contained an appropriate, stably integrated reporter unit rapidly induced gene expression more than a thousandfold. The specificity of the Tet repressor-operator-effector interaction and the pharmacological characteristics of Tc's make this regulatory system well suited for the control of gene activities in vivo, such as in transgenic animals and possibly in gene therapy. PMID- 7792602 TI - Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. AB - Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males. PMID- 7792604 TI - Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin. AB - A soluble adenylyl cyclase was constructed by linkage of portions of the cytosolic domains of the mammalian type I and type II enzymes. The soluble enzyme was stimulated by both forskolin and the alpha subunit of the heterotrimeric guanine nucleotide-binding protein (G protein) Gs (Gs alpha). Expression of the construct complemented the catabolic defect in a strain of Escherichia coli that is deficient in adenylyl cyclase activity. The active, approximately 60 kilodalton enzyme accumulated in the cytoplasmic fraction of E. coli to yield activities in excess of 1 nanomole per minute per milligram of protein. The two sets of transmembrane helices of mammalian adenylyl cyclases are thus not necessary for the catalytic or the most characteristic regulatory activities of the enzyme. This system may be useful for both genetic and biochemical analysis of G protein-regulated adenylyl cyclases. PMID- 7792605 TI - Common mechanisms of visual imagery and perception. AB - Detection of a visual target can be facilitated by flanking visual masks. A similar enhancement in detection thresholds was obtained when observers imagined the previously perceived masks. Imagery-induced facilitation was detected for as long as 5 minutes after observation of the masks by the targeted eye. These results indicated the existence of a low-level (monocular) memory that stores the sensory trace for several minutes and enables reactivation of early representations by higher processes. This memory, with its iconic nature, may subserve the interface between mental images and percepts. PMID- 7792606 TI - Shared neural substrates controlling hand movements in human motor cortex. AB - Voluntary hand movements in humans involve the primary motor cortex (M1). A functional magnetic resonance imaging method that measures relative cerebral blood flow was used to identify a distributed, overlapping pattern of hand movement representation within the posterior precentral gyrus, which contains M1. The observed pattern resembles those reported in nonhuman primates and differs from a somatotopically organized plan typically used to portray human motor cortex organization. Finger and wrist movements activated a wide expanse of the posterior precentral gyrus, and representations for different finger movements overlapped each other and the wrist representation. Multiple sites of activation occurred in the precentral gyrus for all movements. The overlapping representations may mediate motor and cognitive functions requiring coordinated neural processing for finger and wrist actions rather than discrete control implied by somatotopic maps. PMID- 7792607 TI - [Transient ischemic accidents. Results of studies on secondary prevention]. PMID- 7792608 TI - [Health promotion]. PMID- 7792609 TI - [Conference "Human beings in nursing"; Caring as a human characteristic]. PMID- 7792610 TI - [Factors creating preoperative stress]. PMID- 7792612 TI - [Smoking by the fathers and pathology in the children]. PMID- 7792611 TI - [Evaluation of the quality of care. An outline for practical application]. PMID- 7792613 TI - [Outline of osteoporosis]. PMID- 7792615 TI - [The extent of bioethics]. PMID- 7792614 TI - [Knowing how to listen. In a helping relationship]. PMID- 7792616 TI - Urology nurses of Canada: partners in education and care. PMID- 7792617 TI - Pharmacologic erection program: an alternative solution for the man with erectile dysfunction. PMID- 7792618 TI - Use and effectiveness of sexual self-care strategies for interstitial cystitis. PMID- 7792619 TI - Pediatric bladder stimulation therapy. PMID- 7792620 TI - Listening as an art. PMID- 7792621 TI - Helping external catheter wearers to prevent skin breakdown. PMID- 7792622 TI - President's message: preparing urologic nurses to meet the challenges of health care in the next century. PMID- 7792623 TI - Treating stress incontinence with the bladder neck support prosthesis. AB - OBJECTIVE: To evaluate a vaginal device designed to support the bladder neck in women with urinary stress incontinence. STUDY DESIGN: Thirty physically active women completed the study. All underwent urodynamic evaluation at baseline and with the best fitting Bladder Neck Support Prosthesis (Johnson and Johnson Medical Inc., Arlington, Texas) in place. A bladder diary was maintained before enrollment and during 4 weeks of device use. Outcome measures included changes in the number of reported incontinence episodes, urine loss on stress testing, and changes in urodynamic parameters with the device in place. Patient comfort, convenience, and satisfaction were also evaluated. RESULTS: Thirty women completed the study. Twenty-five (84%) were dry with the device in place. Weekly incontinence episodes decreased from ten to three (p < 0.05). Significant changes in functional urethral length, pressure transmission ratio, and Q-tip angle were noted. No evidence of urethral obstruction was noted. The subjects found the device comfortable, easy to use, and convenient. CONCLUSIONS: The bladder neck support prosthesis reduces stress incontinence symptoms significantly and normalizes urodynamic parameters like a colposuspension. PMID- 7792624 TI - Under-users of antenatal care: a comparison of non-attenders and late attenders for antenatal care, with early attenders. AB - Demographic, behavioural, environmental, economic and obstetric history data from the Jamaican Perinatal Morbidity and Mortality Survey were examined to identify characteristics of women who do not attend for antenatal care, or present late instead of early for care, using multiple logistic regression. Non-attenders were more likely to be teenagers, unmarried, in unions of very short duration, smokers and women who felt that friends and relatives were not supportive. Multigravid non-attenders often had short inter-pregnancy intervals and included women who had experienced a post neonatal death. They were often drawn from deprived environments (lack of sanitation, water supplies). Late attenders shared features common to non-attenders (teenagers, unmarried, multigravid). Many however were self employed and did not fit the depressed profile of the non-attender. Most multigravidae who attended late had had previously uneventful pregnancies, including this one. Early attenders had little in common with non-attenders or late attenders. They were older, many had a secondary or tertiary education, were married and were generally middle class women. The group however included high risk multigravidae who had previous pregnancy complications or bad outcomes. Programmes aimed at reaching non-attenders must focus on the wider social and economic needs of these women and must give them a sense of their own power to effect change in their lives. Reaching the late attender will be more difficult and may be unnecessary with the possible exception of the teenager. She needs to be treated in a more sympathetic and non-judgmental way as this is often a high risk pregnancy. More fundamental changes require improved educational and employment opportunities for women as the best consumer is an educated consumer. PMID- 7792625 TI - Why worry about embryos? PMID- 7792626 TI - Overcoming ethnocentrism: how social science and medicine relate and should relate to one another. PMID- 7792627 TI - The effect of third-party payers on the clinical decision making of physical therapists. AB - According to Freidson, third-party payers have eroded the political and economic authority of medicine. To what extent is this also true for alternative practitioners such as physical therapists? The effect of Medicare's restrictive guidelines on physical therapy practice in skilled nursing facilities (SNFs) is examined. SNF physical therapists in Connecticut were surveyed (response rate 99%) using a mixture of open-ended and fixed-alternative responses. Results indicate that SNF physical therapists recognize Medicare criteria and view them as important. Twenty-five to 33% of SNF therapists recommend care based on the guidelines. Younger therapists, therapists with fewer years in the field, and contract therapists are more greatly influenced by the guidelines than older, more experienced, staff therapists (P < 0.08). Those who recommend care based on the guidelines may do so because of possible nonpayment for services already rendered, or because they fear loss of their positions. The majority of Connecticut SNF patients who qualify do receive therapy and Medicare coverage. Therapists may use their knowledge of the guidelines to secure services for their patients, or SNFs may be selecting patients that have the best chances for recovery. Like physicians, SNF physical therapists are under pressure from third party payers to economize and rationalize, but most continue to secure services for their patients. PMID- 7792628 TI - Adolescent psychiatry as a product of contemporary Anglo-American society. AB - Societies differ with respect to medical traditions. The kinds of healers and their emphases vary as a function of culture and social structure. In Western nations, a number of specialty disciplines have evolved. Psychiatry is a creation of the nineteenth century and linked to demographic and social changes of the period. Comparatively little attention has been given to the growth of Adolescent Psychiatry, a sub-discipline that has achieved definition in the last two decades. Its dependence on cultural and political economic transformations is unique insofar as it first required construction of its clientele, namely adolescence itself. The 'disorders' that are the focus of Adolescent Psychiatry appear to be very much linked symbolically and structurally to the unique social pressures impacting on this newly constructed group. The historical and cultural determinants of the developments that have culminated in the evolution of Adolescent Psychiatry are reviewed and discussed. PMID- 7792629 TI - An economic analysis of the resettlement of people with mild learning disabilities and challenging behaviour. AB - New models of care are needed following the closure of long-stay mental handicap hospitals. Based on an evaluation of a recently established assessment and treatment service in south-east England, this paper is concerned with the costs and likely benefits of different patterns of services for people with mild learning disabilities and severely challenging behaviour. Different models of provision are compared in terms of their costs and quality of life opportunities for clients. The assessment and treatment services provided a better understanding of the care needs, and achieved a reduction in challenging behaviours. It was therefore possible to give access to care settings closer to a normal life. For approximately 25% additional expenditure, 20 out of 34 clients who received the service moved to community placements, including three who had been referred following a breakdown in the community. If community care is to be implemented as a policy for clients with learning disabilities and serious challenging behaviours, it is necessary to recognise the financial implications. Better quality of life opportunities for this client group are associated with higher costs. When seen in the dynamic context of the costs and quality of life opportunities of the subsequent care, a high cost assessment and treatment service may be a good investment. On current evidence, the additional benefits of community homes, with a closer association with the local community, and greater freedom for clients is bought only at quite a high cost. PMID- 7792630 TI - Doctor-patient communication: a review of the literature. AB - Communication can be seen as the main ingredient in medical care. In reviewing doctor-patient communication, the following topics are addressed: (1) different purposes of medical communication; (2) analysis of doctor-patient communication; (3) specific communicative behaviors; (4) the influence of communicative behaviors on patient outcomes; and (5) concluding remarks. Three different purposes of communication are identified, namely: (a) creating a good inter personal relationship; (b) exchanging information; and (c) making treatment related decisions. Communication during medical encounters can be analyzed by using different interaction analysis systems (IAS). These systems differ with regard to their clinical relevance, observational strategy, reliability/validity and channels of communicative behavior. Several communicative behaviors that occur in consultations are discussed: instrumental (cure oriented) vs affective (care oriented) behavior, verbal vs non-verbal behavior, privacy behavior, high vs low controlling behavior, and medical vs everyday language vocabularies. Consequences of specific physician behaviors on certain patient outcomes, namely: satisfaction, compliance/adherence to treatment, recall and understanding of information, and health status/psychiatric morbidity are described. Finally, a framework relating background, process and outcome variables is presented. PMID- 7792631 TI - A prepayment scheme for hospital care in the Masisi district in Zaire: a critical evaluation. AB - In most developing countries, government funding allocated to the health services is not sufficient to allow these services to provide appropriate health care accessible to all. Consequently, community financing has received much more attention in recent years and innovative schemes are being explored throughout the developing world. Risk-sharing schemes, like prepayment, are interesting because of their potential redistributive effects. At the end of the eighties, a prepayment scheme for hospital care was experimented with in the Masisi health district in Eastern Zaire. In the present paper, the experiment is described in a chronological way and the results are analyzed and discussed in detail. Although this particular case-study was not successful, it yields important lessons concerning the design, implementation and evaluation of prepayment schemes for hospital health care in developing countries. More specifically, phenomena like adverse selection and moral hazard are discussed. Finally, conditions for success of similar experiments are discussed. These conditions relate mainly to the organization pattern of the district health services system. The Masisi experiment is a nice illustration of the fact that prepayment is not a 'magic bullet': the lessons drawn from it may be of relevancy to health planners intending to implement hospital prepayment schemes in similar settings. PMID- 7792632 TI - Transforming aids prevention to meet women's needs: a focus on developing countries. AB - As currently conceived, the global AIDS prevention strategy consists primarily of three interrelated tactics: (1) encouraging people to reduce their number of sexual partners; (2) promoting the widespread use of condoms; and (3) treating concurrent STDs in populations at risk of HIV. This three-pronged attack, however, is inadequate for meeting the protection needs of many of the world's women. Disproportionately poor and with little power to negotiate the terms of sexual encounters, women often cannot avail themselves of these life-saving strategies. Women need both a new commitment to addressing the underlying inequities that heighten their risk, and new technologies that provide them with a means of HIV protection within their personal control. This article makes the case for restructuring AIDS prevention by describing the growing risk of HIV infection faced by women throughout the world, examining the serious limitations of the contemporary AIDS prevention strategy in meeting women's needs, and exploring how new approaches--including a shift toward a more 'community organizing' approach to AIDS prevention--could help women exert more control over their sexual and reproductive lives. PMID- 7792633 TI - 'A bothersome death'--narrative accounts of infant mortality in Cape Town, South Africa. AB - Traditional measures of health status such as mortality rates and cause-of-death information give limited insight into the role of caregivers and health care providers in infant illness and death. To the extent that the behaviours of these parties can be accurately mapped, they may reveal important sites for effective community interventions and the improvement of medical care. This possibility is explored in relation to infant mortality in Cape Town, South Africa, by analysing verbal histories provided by the caregivers of 70 infants in the course of obtaining police death certification. From these verbal histories it appears that acute respiratory infection and diarrhoeal disease caused the majority of deaths. Infants with a respiratory condition were likely to have been taken for medical attention prior to death. By contrast, the parents of infants with diarrhoeal disease, while more active towards these infants, were less likely to seek medical care--these infants typically being found dead in bed or dying en route to the hospital or clinic. A story of infant death at home following recent medical care was obtained in over half the cases. This study demonstrates a simple method for the examination of the content and structure of lay accounts of illness and death. The implications for health care of such accounts are discussed in terms of the behavioural antecedents of infant mortality due to acute respiratory infections and diarrhoeal disease. PMID- 7792634 TI - The psychosocial problems of sickle cell disease sufferers and their methods of coping. AB - We interviewed 170 sickle cell disease (SCD) patients (mean age 25 years) with a modified version of the Frankfurter Befindlichkeitskala (FBS, 33-item) and the 12 item General Health Questionnaire (GHQ-12), with a view to highlighting the psychosocial issues which worry them, the way they cope with these problems, and the factors associated with these issues. The mean FBS score of SCD patients was comparable with those of insulin dependent diabetics, but significantly higher than that of non-insulin dependent diabetics. The FBS scores were significantly correlated with GHQ-12 scores. Feelings of inadequacy of social contact were significantly associated with high FBS and GHQ scores. Some common complaints were: the limitations illness placed on social life; depressive feelings; abnormal habitus; suicidal ideation during crises; and the burden of illness on the family. They frequently resorted to prayers as a method of coping, as most had no clear ideas on how to deal with these issues. Worries over psychosocial consequences of SCD, seem to add considerably to the burden of illness, and clinicians will offer better care to patients if they routinely enquire into some of these issues and offer health education and counselling in a group setting. PMID- 7792635 TI - Occupational life course and lung cancer risk in men. Findings from a socio epidemiological analysis of job-changing histories in a case-control study. AB - Psychosocial factors in general, and the social and psychological conditions of work and occupation in particular, have attracted little attention to the epidemiological investigation into the occupational-related causes of lung cancer. There is some evidence available concerning the impact of loss events- including job losses--on cancer development. During our research presented in this article, we examined job changes and job transitions in the occupational biography of men with regard to their circumstances in terms of (in )voluntariness both as individual events and the job-changing histories of individuals. We expected the job-changing histories of lung cancer cases to be more involuntary than those of population controls, and vice versa. Our sample contains 391 male case-control pairs. Cases are defined as newly-diagnosed men of German nationality with a histologically- or cytologically-confirmed diagnosis of primary lung cancer. Population controls were drawn randomly from the municipality records of residents and individuals matched to cases 1:1 by age and region. Occupational histories were reconstructed, and information about other classical and suspected risk factors was collected during standardized interviews by trained interviewers. We categorized the reported reasons for job changes, and classified them with respect to voluntariness on a seven-stepped rating scale from -3 'very involuntary' to +3 'very voluntary', defining relations within the empirically established categories. The job-changing histories of individuals are described by using the average score of voluntariness. We measured the degree of voluntariness for the occupational history: (1) by the rounded average score; and (2) by the quintiles of the average score. On the basis of individuals matched odds ratios (OR) estimates are derived for the score of voluntariness unadjusted and adjusted for smoking, asbestos exposure and socio-economic group by conditional logistic regression. The investigation into job-changing histories using the average score of voluntariness lead to similar results for both measuring methods for the total study group. When the rounded score was used, job changing histories which were assessed as 'very involuntary' and 'involuntary' (score -3 and -2) showed an elevated odds ratio of adjusted 1.41 (95%-CI: 0.57; 3.48), and when they were assessed as 'moderately involuntary' (score -1) the adjusted odds ratio was 1.59 (95%-CI: 1.02; 2.48), as compared with job-changing histories assessed as neutral (score 0). When the degree of voluntariness was measured by quintiles, the first quintile (score -3- < -0.6) showed an elevated risk of adjusted OR 1.36 (95%-CI: 0.79; 2.36) as compared to the third quintile (score -0.2- < -0.1).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7792636 TI - Talking about the pain: a patient-centered study of low back pain in primary care. AB - Despite considerable research, low back pain (LBP) often proves resistant to treatment. This study was designed to increase the understanding of low back pain through access to patients' perceptions, beliefs, illness behaviors and lived experiences. The findings are based on focus groups, individual interviews and participant observation conducted in primary care practices and community settings in three regions in Israel. Inclusion criteria for the interviews and groups include age greater than 18 years and a history of at least one episode of LBP. Seventy-six LBP subjects between the ages of 18 and 67 (mean 39.5) participated, 65% male and 35% female. The analytic method is content analysis, consisting of a formal, multi-step process designed to elucidate inherent patterns and meanings. This research finds that LBP subjects articulate a rich world of pain sensation, awareness and meanings. From subjects' own words and experiences we present a patient-centered classification system of backache symptoms based on typical pain intensity, dysfunction, duration and treatment. An elaborate system of explanatory models of LBP and a typology of dominant coping styles designed to either minimize pain or maximize function are also derived. Subjects choose multiple conventional and alternative treatments based on 'what works', and articulate ample criticisms of and suggestions for the medical system. In addition, we find that variations in the social construction of the back pain experience vary sharply, even between similar neighboring communities. Given the difficult state of diagnosis and treatment and the frustration of practitioners, attempts at greater understanding of patients' health beliefs, experiences, and behaviors are warranted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792637 TI - Treatment of childhood diarrhea in rural Egypt. AB - The Egypt National Control of Diarrheal Diseases Project, implemented between 1983 and 1991, is widely regarded as one of the most successful national oral rehydration programs. Data from a longitudinal household survey conducted in 1990 91 in rural Egypt indicate substantial increases in both knowledge and use of oral rehydration salts during the 1980s. However, the same data show that treatment of acute diarrheal episodes is still far from optimal. In particular, the use of oral rehydration during diarrheal episodes is far from universal, the prescription of antibiotics is still too frequent, and antidiarrheal drugs of no therapeutic value are still widely used. Analysis of the factors associated with different treatment patterns shows that children with severe diarrhea, those aged 6-23 months and those from poor households were more likely to be given ORS; boys were somewhat less likely to receive ORS than girls, but mother's education showed no consistent effects. The type of treatment received is strongly influenced by the source of care. Government clinics are more likely than private physicians or pharmacies to prescribe ORS, whereas children taken to the latter two sources of care are more likely to be given antibiotics and antidiarrheals. To improve diarrhea treatment patterns in Egypt, not only must the public service educational campaign be reinstated and strengthened, but training programs must also be targeted at the treatment practices of private physicians. PMID- 7792638 TI - Habitat destruction syndrome. PMID- 7792639 TI - [Principal complications in the hemodialyzed patient]. PMID- 7792640 TI - [Nutritional hygiene for the dialyzed patient]. PMID- 7792641 TI - [Course of a hemodialysis session. The nurse's role]. PMID- 7792642 TI - [Middle and long-term follow-up of dialyzed patients]. PMID- 7792643 TI - [Education in home dialysis and autodialysis. The nurse's role]. PMID- 7792644 TI - [Psychological effects of hemodialysis]. PMID- 7792645 TI - [The quality of care in a hemodialysis unit]. PMID- 7792648 TI - [The nurse and the dialyzed patient]. PMID- 7792647 TI - [The future of the dialyzed patient]. PMID- 7792646 TI - [Kidney transplantation. Indications and preparation of the graft]. PMID- 7792649 TI - [Practical application of nursing ethics]. PMID- 7792650 TI - [The nurses' responsibility. Professional responsibility and the proper role of the autonomous nurse]. PMID- 7792651 TI - [Chronic kidney failure]. PMID- 7792652 TI - [The unbearable gap in nursing education and practice]. PMID- 7792654 TI - [Extrarenal purification by hemodialysis]. PMID- 7792653 TI - [Lithium salts]. PMID- 7792656 TI - [Practice of home hospitalization]. PMID- 7792655 TI - [Clinical significance of home hospitalization]. PMID- 7792657 TI - [The institutional coffee habit. An aspect of wearing-out]. PMID- 7792658 TI - [Therapeutic placement in families. Dun-sur-Auron specialized hospital center]. PMID- 7792660 TI - [Group therapy in psychiatric medical centers]. PMID- 7792659 TI - [Activities of a department. Parameters and indices]. PMID- 7792662 TI - [Black nights]. PMID- 7792661 TI - [Psychiatric home hospitalization. Preface]. PMID- 7792663 TI - [Psychiatric home hospitalization]. PMID- 7792664 TI - [Breast carcinoma: successful early diagnosis, increased mortality]. PMID- 7792665 TI - [Side effects and complications of intra-arterial tumor therapy--experiences with 577 interventions]. PMID- 7792666 TI - [Parametric images of cerebral blood volume with T1 FLASH sequences]. PMID- 7792667 TI - [Cystic lymphangioma of the mesentery--a rare space-occupying lesion of the abdomen]. PMID- 7792670 TI - Human susceptibility to indoor contaminants. AB - Indoor environmental pollutants can act as irritants, allergens, carcinogens, or infectious agents. This chapter focuses on human susceptibility to indoor environmental pollutants, here defined as inherent factors that alter exposure response relationships. The host defense system is an important determinant of human susceptibility and is composed of two portions: nonspecific immunity and specific immunity. Pollutants elicit responses from many components of the human host defense system, and human susceptibility results from biologic variability in these components. Nonspecific immunity responds to stressors based on physicochemical properties. Components include mucociliary clearance, the epithelial barrier, airway surface fluid, and neural reflexes. Specific immunity recognizes and responds to unique peptide or carbohydrate sequences present on the foreign agent, and components of the response may include lymphocytes, basophils, mast cells, and immunoglobulins. Irritants typically stimulate nonspecific immunity, allergens stimulate specific immunity, and infecting organisms and carcinogens interact with both. Additional inherent factors that may alter the toxicity of an agent include genetic background, the presence of disease or specific organ pathology, age, gender, body weight, nutritional, hormonal, and central nervous system status. Understanding the basis for human susceptibility to indoor environmental pollutants can assist in implementing practical strategies for managing indoor air quality. PMID- 7792669 TI - Biologic contaminants. AB - Dr. Seltzer lays the groundwork for a discussion of the importance of a healthy environment by pointing out that most Americans spend at least 90% of their time indoors. He describes conditions that promote biologic contamination, ways that these contaminants induce illness, the key components of any evaluation of an indoor environment, and methods of decontamination and prevention. PMID- 7792668 TI - [Detection of a hepatic artery aneurysm with color-coded duplex ultrasound]. PMID- 7792672 TI - The behavioral effects of indoor air pollutants. PMID- 7792671 TI - Irritation and odor as indicators of indoor pollution. AB - Both irritation and odor figure prominently in complaints about indoor air. Irritation poses the greater problem since it arguably represents an adverse health effect per se and since its sources are often difficult to locate. There exist various potential assays for irritation, some better for validation of symptoms and some better for research on structure-activity relations. One animal assay, the respiratory depression technique, has produced measures of irritant potency in good accord with sensory psychophysical measurements in humans. Both the animal and human data point toward common physicochemical determinants of potency, especially for the weak irritants that often exist in indoor environments. For the foreseeable future, the assessment of odors in indoor environments will need to proceed as in the past, as a psychophysical measurement rather than as a chemical measurement. Methodologies for odor measurement continue to evolve. The evaluation of their usefulness in field settings must ultimately stand against a criterion of validity that has to date proved elusive to establish. PMID- 7792674 TI - The medical evaluation. PMID- 7792673 TI - The sick-building syndrome. AB - The sick-building syndrome is a poorly defined term whose use should be discontinued. In the majority of cases, engineering problems and pollutant sources can be identified that contribute to the generation of complaints. Although psychosocial factors are likely to exacerbate underlying complaints, they should not distract from identifying solutions. PMID- 7792675 TI - A systematic approach to indoor air quality for the building manager. PMID- 7792677 TI - Indoor air quality: research needs. AB - Areas of research for which the author finds a need include source characterization, exposure assessment, health effects, risk assessment, and solutions that will prevent or mitigate pollution. Policies regarding radon are cited to provide examples of directions that other IAQ policies can follow. PMID- 7792678 TI - Creating healthy indoor environments. A road map for the future. AB - This road map for the future describes 12 steps toward the creation of healthy indoor environments. Pointing out that funding for indoor air issues pales in comparison to that spent on outdoor pollution, the author argues that a multidisciplinary approach is necessary to improve the existing knowledge base concerning IAQ. PMID- 7792676 TI - The legal aspects of indoor air and health. PMID- 7792680 TI - Ventilation. AB - This chapter begins with an overview of the history of ventilation guidelines, which has led to the guidelines that are in effect today. Of particular interest is the most recent return in the past 5 years to ventilation rates that more closely reflect a mean or average of the range of guidelines that have existed over the past century. OSHA's and the EPA's recognition of the need to operate ventilation systems in buildings in an accountable manner is also of note. Of even more interest is the resurgence of the concept of minimum mixing and once through ventilation air that has been pursued in parts of Northern Europe for the past 10 years, and in a school that is being designed with this concept in New Hampshire. In addition, the design concept of equipping office buildings with low pressure drop high efficiency particle filtration to remove fine particles from all of the air that is supplied to the occupants is being used increasingly in the U.S. This chapter also presents an overview of the various types of ventilation systems found in homes and commercial office buildings and the common indoor air quality problems that may be associated with them. It also offers an overview of common HVAC evaluation techniques that can be used to determine if a ventilation system is performing in a manner that makes sense for the use of the space and the needs of the occupants. Are the occupants receiving a reasonable supply of outdoor air? Is the air that they receive of reasonable quality? Are obvious pollutants being exhausted? Ventilation systems have become extremely complex and more difficult to run and maintain over the past 40 years. This trend will continue to drive the need for professionally maintained HVAC equipment that is serviced and run by individuals who are accountable for the quality of the air that the system delivers. PMID- 7792679 TI - Aerobiology of the indoor environment. AB - This review of aerobiology focuses on the principles of aerobiology, the effect of airborne agents on human health, and the characteristics of indoor aerosols and outdoor aerosols that enter the indoor environment. A discussion of representative monitoring describes observational, bulk, and air sampling. PMID- 7792681 TI - Physical factors in the indoor environment. AB - This comprehensive chapter presents a discussion of physical factors in the nonindustrial indoor environment that affect human health, comfort, productivity, and well-being. Areas stressed include the thermal environment, light, noise, and other mechanical energy. PMID- 7792682 TI - The environmental evaluation: commercial and home. PMID- 7792683 TI - Why, how, and when? Why did this happen? How should it be treated? When will there be a cure? PMID- 7792684 TI - Estrogen and progesterone receptors in human meningiomas: biochemical and immunocytochemical evaluation. AB - BACKGROUND: The observation that human meningiomas are rich in steroid hormone receptors has led to the hypothesis that their growth may be hormonally dependent. This study aims to correlate the biochemical expression of estrogen (ER) and progesterone receptors (PgR) with their nuclear immunoreactivity in a large series of meningiomas. METHODS: The occurrence of ER and PgR in patients with primary untreated meningiomas was studied with a dextrancoated charcoal method (DCC) and the results were compared with those of an immunocytochemical assay (ICA). Progesterone and estrogen receptor determinations were performed on 103 and 99 meningiomas respectively using the DCC assay. Forty-six and 44 of these samples were immunocytochemically evaluated for the presence of PgR and ER respectively. RESULTS: Of the 46 samples evaluated by both the methods, 89% were found PgR positive by DCC and 70% by ICA. The overall concordance between PgR-DCC and PgR-ICA was 80%. Whereas low concentrations of ER were found in 8/44 samples (18%) assayed by DCC, specific staining was never observed in any of the samples tested by ICA. CONCLUSIONS: Our findings confirm that the majority of meningiomas are devoid of ER and that the biochemical evidence of PgR correlates well with the nuclear localization of progesterone receptors determined by immunocytochemistry. PMID- 7792685 TI - Cystic meningiomas. AB - BACKGROUND: Meningiomas are generally solid tumors and are easily diagnosed by CT scans and MRI scans. Rarely are these tumors associated with cysts that can cause a confusion in the pre- and intraoperative diagnosis. Cysts associated with meningiomas may be intratumoral or peritumoral. METHODS: The authors conducted a retrospective study of the seventeen meningiomas, out of a total number of 232, which were associated with cysts. The cysts were classified based on their relationship to the tumor. The patients' sex, age group, location of the tumor, and pathological type of tumor were also analyzed. RESULTS: The 17 cases of cystic meningioma formed 7.3% of the meningiomas seen between 1984 and 1993. Eleven of these were intratumoral and 6 peritumoral. One case had both intra- and peritumoral cysts. The tumors were found mostly in the fourth and fifth decades of life. Histologically, all the peritumoral cysts except one were associated with meningotheliomatous meningiomas. Tumors with peritumoral cysts were more common in males. Intratumoral cysts, more common in females, were angioblastic or meningotheliomatous on histopathology. Only one case was an anaplastic meningioma. CONCLUSION: Cysts associated with meningiomas, although uncommon, are certainly not rare. The peritumoral and the intratumoral cysts form distinct subtypes needing separate consideration. Cystic meningiomas are only rarely malignant. PMID- 7792686 TI - Dysembryoplastic neuroepithelial tumor: report of three cases. AB - BACKGROUND: Dysembryoplastic neuroepithelial tumor (DNT) is one of the mixed neuronal-glial tumors that should be differentiated from low-grade gliomas. The recognition and correct diagnosis of DNT is important because this tumor is curable by excision. METHODS: We report three cases of histologically proven DNTs with various image studies performed preoperatively and describe characteristic findings of them, as well as those of previous reports. RESULTS: In our three cases, computed tomography (CT) showed a well-defined, nonenhancing hypodense area. Magnetic resonance imaging (MRI) demonstrated a cortical mass of hypointensity on T1- and of marked hyperintensity on T2-weighted images. I-123 IMP or Tc-99m-HMPAO single-photon emission computed tomography (SPECT) images showed marked hypoperfusion of the lesion. Thallium-SPECT showed no uptake. CONCLUSIONS: I-123-IMP, Tc-99m-HMPAO, and Thallium-SPECT images, as well as CT and MRI, may be helpful in distinguishing DNT from low-grade gliomas. PMID- 7792687 TI - Epidermoid tumors of the fourth ventricle. AB - BACKGROUND: Epidermoids of the brain are rare tumors. Their fourth ventricle localization is about the rarest localization. No series of such tumors has been reported. Their manifestations and management are therefore not well understood. METHODS: Four epidermoid tumors of the fourth ventricle were collected over a period of 39 years from the neurosurgical units of the American University of Beirut Medical Center and the Orient Hospital. These were retrospectively studied and the medical literature reviewed. RESULTS: Epidermoids of the brain form 1% of all brain tumors, and those located in the fourth ventricle are 16.7% of the epidermoids. They rarely present symptoms of increased intracranial pressure. They commonly present in adults with only cerebellar signs. The duration of symptoms may be short, medium, or long. The diagnosis, when clinically suspected, should be confirmed by magnetic resonance imaging. An early diagnosis is the key for a good outcome. CONCLUSION: Although a rare condition, these tumors can be lethal if not treated. Total excision should be attempted. Because this tumor is very slow-growing, a near-total excision is acceptable in cases where complete removal may endanger function or life. PMID- 7792688 TI - Central neurocytoma with hemorrhagic onset. AB - A case of central neurocytoma with spontaneous intraventricular hemorrhage is reported. A 23-year-old man, 2 years after experiencing intraventricular hemorrhage, developed severe headaches. The magnetic resonance image showed a mixed intense mass in the lateral ventricle with associated hydrocephalus. The tumor mass was totally removed. The tumor was histologically diagnosed as central neurocytoma. Review of the computed tomography taken 2 years ago showed not only the hemorrhage but also a mass in the left lateral ventricle. This emphasizes that central neurocytoma should be considered in the differential diagnosis of patients with either intraventricular hemorrhage or hemorrhagic tumor. PMID- 7792689 TI - Extradural tumor causing spinal cord compression in Klippel-Trenaunay-Weber syndrome. AB - BACKGROUND: Myelopathy in Klippel-Trenaunay-Weber syndrome is uncommon but has been reported secondary to spinal vascular malformations. REPORT: A patient with Klippel-Trenaunay-Weber syndrome who presented with spinal cord compression from a spinal extradural mass lesion (angiomyolipoma) is described. DISCUSSION: This association has not been reported previously but is consistent with the segmental vascular abnormalities observed in Klippel-Trenaunay-Weber syndrome. PMID- 7792690 TI - A case of spinal low-grade astrocytoma with exophytic and intracranial extension. AB - BACKGROUND: Ventral exophytic growth of a spinal intramedullary glioma into the cranial cavity is an unusual condition. CASE DESCRIPTION: A 16-year-old boy was admitted because of lower cranial nerve dysfunction and acute hydrocephalus. Magnetic resonance images showed an intramedullary mass lesion in the upper cervical spinal cord with exophytic extension into the medullary and prepontine cisterns. The patient underwent suboccipital craniectomy and C1-2 laminectomy for decompression and histologic evaluation. The histopathologic findings were characteristic of astrocytoma grade II. Although radiotherapy was performed, the patient died 7 months later. CONCLUSIONS: This is considered to be a rare case of spinal low-grade astrocytoma with ventral exophytic intracranial extension. PMID- 7792691 TI - Cryoprobe-assisted removal of spinal cord tumors: technical note. AB - The application of a cryosurgical contact probe to assist in the removal of intraspinal neoplasms is described. Most often used by ophthalmic surgeons for intraocular extraction purposes, these .89-3 mm cryoprobes provide an ideal safe "handle" when attached to intramedullary or extramedullary spinal cord tumors and facilitate dissection and removal with standard microsurgical techniques. PMID- 7792692 TI - Intracerebral hematoma in patients with ruptured cerebral aneurysms. AB - BACKGROUND: Intracerebral hematoma from ruptured aneurysms is one of the unfavorable factors for outcome in patients with subarachnoid hemorrhage. In this study, the clinical characteristics of intracerebral hematoma in patients with ruptured aneurysms were examined. METHODS: The subjects were 512 patients who had been admitted by day 3 after aneurysmal rupture without episodes of rebleeding before the initial computed tomography (CT) scan. They were divided into two groups according to the findings of initial CT; groups 1 and 2 comprised patients with and without intracerebral hematoma, respectively. RESULTS: Of the 512 patients, intracerebral hematoma was observed in 98 (19%). The incidence of intracerebral hematoma was higher in patients with distal anterior cerebral and middle cerebral artery aneurysms, compared with those at other sites (both, p < 0.01). Interhemispheric, callosal, and temporal lobe/sylvian hematomas were observed more frequently in patients with anterior communicating, distal anterior cerebral, and middle cerebral artery aneurysms, respectively, than in those with aneurysms at other sites. The incidence of rebleeding was 22% in group 1 and 14% in group 2 (p < 0.05). Clinical grades on admission were higher and outcome at 6 months after onset was less favorable in group 1 than in group 2 (both, p < 0.01). The larger the intracerebral hematoma, the higher was the clinical grade and the less favorable the outcome. However, when comparing management and surgical outcome under the same clinical grades, there was no significant difference between the two groups. CONCLUSIONS: There was a close correlation between the site of hematoma and that of the ruptured aneurysm. Poor outcome in patients with intracerebral hematoma seems to be related to severity of clinical grade on admission. PMID- 7792694 TI - The different classification systems for astrocytomas. PMID- 7792695 TI - Glia: the brain's other cells. PMID- 7792693 TI - Factors leading to early recurrence of carotid plaque after carotid endarterectomy. AB - BACKGROUND: Carotid endarterectomy to remove atherosclerotic plaque restores blood flow and reduces the risk of cerebral ischemia. In some patients, however, postoperative plaque recurrence reduces the clinical benefit of carotid endarterectomy. METHODS: Using duplex ultrasound scanning, we evaluated carotid artery restenosis in 63 endarterectomy patients followed for an average of 26.6 months after surgery. RESULTS: During follow-up, two-thirds of the patients showed some observable vessel wall thickening. A negative correlation was found between years since smoking cessation and recurrence of carotid plaque. Maximum benefit was seen when smoking cessation occurred at least 1 year before endarterectomy. The least benefit was seen when smoking continued or when cessation occurred within 1 year of endarterectomy. CONCLUSIONS: Smoking status was the only cardiovascular risk factor independently and significantly associated with recurrent plaque thickness. PMID- 7792697 TI - The 47th annual meeting of the Neurosurgical Society of America, May 22-25, 1994. PMID- 7792696 TI - The erythrocyte sedimentation rate: an interface between science and the law. AB - Excerpts from the deposition of a medical expert appearing for a female plaintiff in a malpractice action dealing with a postoperative disk space infection are presented. Much of the issue centered about the erythrocyte sedimentation (ESR) rate 4 months postdisk surgery (ESR = 23 mm/hr). The expert testified that the ESR will, after an initial rise, return to normal levels in the face of progressive symptomatology and inflammatory bone change. The pertinent literature cited indicates that the elevated sedimentation rate in infection not only persists, but escalates and remains in an elevated state until appropriate therapy is instituted. PMID- 7792699 TI - The treatment of hydrocephalus: a brief guide to shunt selection. AB - The placement of a cerebrospinal fluid shunt system is a procedure that most neurosurgeons feel comfortable performing. The procedure is fraught with many pitfalls and the choices of equipment are staggering. We review the recent literature on shunt systems. We describe the newer shunt systems and procedures and identify possible roles for them in shunt procedures by the neurosurgeon in practice. PMID- 7792698 TI - Whose life is it anyway? PMID- 7792700 TI - A new shunt for hydrocephalus that relies on CSF production rather than on ventricular pressure: initial clinical experiences. AB - BACKGROUND: Ventricular shunting for hydrocephalus is one of the surgical procedures most frequently associated with complications. When the hydrocephalus is secondary to arachnoiditis the prognosis is usually poor. METHODS: Twenty-six patients with hydrocephalus secondary to chronic arachnoiditis due to meningeal cysticercosis were treated with a new ventriculoperitoneal shunt whose design is based on the rate of cerebrospinal fluid (CSF) production and shunt resistance rather than on ventricular pressure, which has been the principal parameter for most other shunting devices. RESULTS: The shunt has remained functional in 25 patients (96%). A peculiar response was documented in all cases by sequential CT scans; i.e.; the size of the ventricular cavities showed gradual reduction and about 1 month postsurgery the ventricles had returned to normal size. In all cases, fast clinical improvement was documented within the first 2 days after surgery with remission of all symptoms of intracranial hypertension. Improvement has continued for a mean follow-up of 9 +/- 2 months. In one case, the shunt was occluded a month after surgery, was withdrawn, and was replaced by a conventional shunt. CONCLUSIONS: Our initial results contrast with the experience with other shunts, which in these patients have a rate of 50% occlusion within the first 4 months after surgery. Although a long-term follow-up is mandatory, it seems that the treatment of hydrocephalus by a shunt devoid of valve mechanisms, with drainage capacity limited to physiological parameters of CSF production, could avoid the unacceptable high frequency of overdrainage and occlusion that are the main complications of shunting devices that operate in relation to ventricular pressure. PMID- 7792701 TI - Shunt failure in adult hydrocephalus: flow-controlled shunt versus differential pressure shunts--a cooperative study in 289 patients. AB - BACKGROUND: In order to assess the efficiency of flow-controlled shunts in reducing shunt failure in the treatment of adult hydrocephalus (with a special focus on overdrainage complications), a series of 289 patients was analyzed through a retrospective and comparative study performed in three neurosurgical departments. METHODS: A group of 142 adult patients suffering from hydrocephalus were operated on using a conventional differential pressure (DP) shunt and compared with a group of 147 adult patients operated on using flow-controlled (FC) system (Orbis-Sigma, Cordis). Only the first complication, which required a surgical revision within the first 2 years after shunt implantation, was taken into account for each patient and analyzed using life-table methods. RESULTS: The actuarial risk of shunt infection in the two groups is respectively 8.3% and 10.9% at 1 year (nonsignificant difference). The actuarial risk of mechanical complications at 1 year is 38% for the DP patients and 10% for the FC patients (p = 0.0001); this difference is largely due to a decrease of complications related to overdrainage phenomenon (14/142 subdural collections were observed in the DP group versus 1/147 in the FC group) (p = 0.0001). CONCLUSION: The conclusion of this cooperative and retrospective study is that the use of a flow-controlled system decreases the risk of mechanical complications related to the hydrodynamic properties of the shunts used in the treatment of adult hydrocephalus, especially those related to overdrainage. PMID- 7792703 TI - A no-touch technique protocol to diminish cerebrospinal fluid shunt infection. AB - BACKGROUND: Cerebrospinal fluid (CSF) shunts become infected primarily by bacterial organisms indigenous to the patient's skin flora, but bacteria from the operating room environment, hospital, or no obvious source may also infect a shunt. To decrease the incidence of shunt infection, a no-touch technique protocol was developed and utilized in a prospective manner. METHODS: A before after trial analysis was performed to compare the infection rates between patients who had CSF shunts placed using the no-touch technique protocol versus patients who had surgery without the protocol. Patients were stratified by age, etiology of hydrocephalus, type of shunt surgery, and presence of a contaminated skin wound, namely, tracheostomy, gastrostomy-jejunostomy, colostomy, or halo. The differences in infection rates were analyzed with the Fisher exact test with midpoint value correction, and standard statistical methods were used to calculate the 90% confidence interval odds ratio and number to treat. RESULTS: The no-touch technique protocol resulted in a clinically significant threefold decrease in shunt infection rate from 9.1% to 2.9% (p = 0.058 at 0.10 level, odds ratio 0.305, confidence interval 0.084-1.11), and a near threefold decrease in the infection rate per patient from 11.3% to 3.9% (p = 0.032 at 0.10 level, odds ratio 0.243, confidence interval 0.065-0.906). CONCLUSIONS: The no-touch technique protocol as described herein is a useful method to decrease shunt infection. A larger prospective, randomized, multicenter clinical trial is encouraged to stringently assess the efficacy of the protocol. PMID- 7792702 TI - Hydrothorax from intrathoracic migration of a ventriculoperitoneal shunt catheter. AB - BACKGROUND: The intrathoracic complications of the ventriculoperitoneal (VP) shunt are very rare. We report an unusual case of VP shunt complication with intrathoracic migration, associated with pleural effusion in a 55-year-old man. METHODS: We reviewed the seven cases reported in the literature and the mechanism of shunt-tip migration and preventive measures are presented. RESULTS: The patient was successfully managed with revision. The catheter was retrieved and replaced in the peritoneal cavity. CONCLUSIONS: With VP shunting, it is important to keep in mind the possibility of peritoneal shunt-tip migration into the chest. To prevent this kind of complication, we stressed precise location of a subcutaneous tunneling device above the ribs during subcutaneous passage. PMID- 7792704 TI - Ruptured aneurysm associated with arachnoid cyst: intracystic hematoma without subarachnoid hemorrhage. AB - BACKGROUND: It is well-known that arachnoid cysts of the middle fossa are associated often with chronic subdural hematomas and/or intracystic hemorrhages. However, reports of an arachnoid cyst associated with an aneurysm are rare. CASE DESCRIPTION: A 45-year-old man was admitted with headache due to intracystic hemorrhage in the sylvian fissure, associated with a saccular aneurysm at the bifurcation of the internal carotid artery. The aneurysm ruptured into the arachnoid cyst, without causing a subarachnoid hemorrhage. Subsequently, the neck of the aneurysm was clipped successfully. The patient's postoperative course was uneventful, and there was no vasospasm. CONCLUSIONS: This is the first reported case of an intracystic hematoma due to a ruptured aneurysm. We discuss the possible etiology of the association between the aneurysm and the arachnoid cyst, and the formation mechanism for the intracystic hematoma that did not result in a subarachnoid hemorrhage. PMID- 7792705 TI - Endovascular management of biopsy-related posterior inferior cerebellar artery pseudoaneurysm. AB - We present a case of a posterior inferior cerebellar artery pseudoaneurysm with subarachnoid hemorrhage resulting from a transoral head and neck tumor biopsy. The pseudoaneurysm was managed using transcatheter coil embolization. PMID- 7792707 TI - Giant cephalhematoma in a 15-year-old boy. Unilateral amaurosis as the main complication. AB - BACKGROUND: The term "cephalhematoma" is applied to a collection of blood under the periosteum of a skull bone. It most frequently occurs in the neonatal period and is rare at other times of life. METHODS AND RESULTS: We report on a 15-year old boy with a subperiosteal hematoma involving the whole cranial surface. Surgical drainage was performed. In the immediate postoperative course, the patient developed a progressive decrease in the right eye visual acuity. An orbital computed tomographic scan revealed the retro-orbital subperiosteal extension of the hematoma. A second surgical procedure was necessary to obtain visual recovery. CONCLUSIONS: The occurrence of cephalhematoma in adults is exceptional. However, it may lead to serious complications. Surgical treatment should be aimed to avoid retro-orbital extension of the hematoma. PMID- 7792706 TI - Superficial temporal artery to superior cerebellar artery anastomosis via the presigmoid retrolabyrinthine transtentorial approach. AB - BACKGROUND: The conventional method for performing superficial temporal artery to superior cerebellar artery (STA-SCA) anastomosis is applied to ischemic lesions in the posterior circulation via the temporobasal approach. However, this approach can be difficult and presents limitations due to the deep and narrow surgical field. METHODS AND RESULTS: STA-SCA anastomosis using the presigmoid retrolabyrinthine transtentorial approach was performed, in which a large skin incision was required for the isolation of the STA, compared to that associated with the petrosal approach as described in previous reports. The superior petrosal sinus was sacrificed, and the tentorium cerebelli was cut up to the level of the incisula. Being very close to the surface opening, the SCA was approached easily at the ambient portion without any danger to the vein of Labbe. The SCA ran perpendicularly upward in the surgical field, which was advantageous in performing the anastomosis. CONCLUSION: The presigmoid retrolabyrinthine transtentorial approach may provide a better surgical strategy than the temporobasal approach in performing STA-SCA anastomosis. PMID- 7792708 TI - Pathogenesis and treatment of growing skull fractures. AB - BACKGROUND: Growing skull fractures are poorly understood complications of pediatric skull fractures. METHODS: A retrospective review of skull fractures at our institution from 1980-1993 revealed 10 patients with growing skull fractures. The age at injury ranged from 1-144 months, with 9 of 10 patients being under one year of age. The etiology of these fractures included falls, motor vehicle accidents, and child abuse. On average, growth of the fracture was diagnosed 14 months after the initial injury. RESULTS: Six patients have had magnetic resonance imaging (MRI) with one demonstrating leptomeningeal cyst herniation, two having brain herniation, and three having both brain parenchyma and leptomeningeal cyst herniation. All patients had malacic cortex underlying the fracture, but there was no evidence of intracranial hypertension. Nine patients have undergone craniotomy with excision of granulation tissue and gliotic brain, dural repair, and cranioplasty using surrounding normal skull. There were no surgical complications or recurrences. CONCLUSIONS: Brain/leptomeningeal cyst herniation through a dural rent, without MRI evidence of increased intracranial pressure, implicates physiologic growth and brain cerebrospinal fluid (CSF) pulsations as the cause of fracture enlargement. PMID- 7792709 TI - Primary intracranial plasma-cell granuloma: a case report and review of the literature. AB - BACKGROUND: Plasma-cell granulomas, which are characterized by the non-neoplastic proliferation of plasma cells, are primarily found in the lungs and upper respiratory tracts, and are extremely rare in the central nervous system. METHODS: An intracranial tumor of an 11-year-old boy was evaluated by histologic and radiologic examination. RESULTS: An 11-year-old boy had a 2-month history of mild headache and nausea. A computed tomography scan showed a round, slightly high-density mass surrounded by marked edema in the left frontal lobe. On magnetic resonance imaging (MRI), the mass had a slightly high signal intensity on the T1-weighted image and marked low signal intensity on the T2-weighted image. It was heterogenously enhanced with gadolinium-DTPA. Microscopic examination demonstrated a non-neoplastic mixed cell population with a predominance of plasma cells. Immunohistochemical staining revealed that it was characterized by a polyclonal plasma cell population. CONCLUSION: Our extensive search of the literature indicated this to be the ninth reported case of intracranial plasma cell granulation. The MRI was very useful for evaluating the extent of the intracranial lesions. The tumor was removed surgically and did not recur during a 2-year follow-up with no radiation therapy. PMID- 7792711 TI - Mycosis fungoides with central nervous system involvement--a case report: T-cell lymphoma of the brain. AB - Mycosis fungoides is a rare malignant T-cell lymphoma, involving mainly the skin. It can, in 50%-75% of cases, involve visceral organs and, in 11%-14% of cases, metastasize to the central nervous system. The prognosis is poor. A case with cerebral involvement is presented and the relevant literature reviewed. PMID- 7792710 TI - Indications for the surgical management of central nervous system blastomycosis. AB - BACKGROUND: Blastomycotic infections of the central nervous system (CNS) occur infrequently. The medical literature concerning blastomycosis of the CNS contains little information regarding indications for surgery. METHODS: We report five cases of CNS blastomycosis that required surgery: four intracranial and one intraspinal. One patient had a prior diagnosis of sarcoidosis, whereas none of the others had been diagnosed with any other systemic illness. The patients were evaluated with plain x rays as well as with computed tomography or magnetic resonance imaging. RESULTS: Four of these patients had extradural abscesses that required surgical drainage as well as debridement of granulomatous tissue and infected bone. The remaining patient had an intracerebellar abscess. Postoperatively, three patients were treated with amphotericin B, one with amphotericin B and ketoconazole, and one with an experimental protocol of fluconazole alone. All of the patients recovered without sequelae of seizures, recurrence of disease, or reaction to pharmacotherapy, although one patient had transient renal insufficiency due to amphotericin B. CONCLUSIONS: Our experience with CNS blastomycosis managed surgically is reported. We propose three general surgical indications for these patients: mass lesions, diagnostic biopsy, and osteomyelitis refractory to pharmacotherapy. PMID- 7792712 TI - Control of tumor cell proliferation and radiation therapy. PMID- 7792713 TI - Lighted mirror for microneurosurgery. AB - We describe a newly developed, lighted mirror that provides enough luminous intensity to obtain a clear image in deep operative fields under high magnification. Through the initial neurosurgical procedures in which it was tested, the mirror proved particularly useful for inspecting the ventral aspect of the fifth nerve in a microvascular decompression for trigeminal neuralgia, and for observing the fundus of the internal auditory meatus after removal of an acoustic neuroma to ensure no residual tumor. PMID- 7792715 TI - Retirement: what to do? PMID- 7792714 TI - Pneumocephalus after thoracotomy. AB - BACKGROUND: Pneumocephalus is a well-known phenomenon in which a fistula between the thoracic cavity and the subarachnoid space is one of its rare etiologies. METHODS: We report a new case of pneumocephalus after thoracotomy and review eight similar cases in the literature. RESULTS: In all cases, an operation was carried out for an intrathoracic neoplasm located at the apex with chest wall invasion. In the presence of symptoms, the diagnosis of pneumocephalus and identification of the subarachnoid pleural fistula were differently supplied by radiographic and isotopic exams. In the follow-up, one patient was affected by meningitis and two patients died. CONCLUSIONS: The occurrence of pneumocephalus must be considered when neurologic problems emerge after thoracotomy. It appears that if conservative treatment fails, surgical closure of the fistula via thoracic or neurosurgical approach is indicated. PMID- 7792716 TI - What is a Torkildsen shunt? PMID- 7792717 TI - The future of neurosurgery: a perspective on the next 30 years. PMID- 7792718 TI - Modulation of dopamine D1-mediated turning behavior and striatal c-fos expression by the substantia nigra. AB - In order to study the possible contribution of the substantia nigra (SN) in the positive interaction between dopamine D1 receptor agonists and glutamate antagonists in unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, the effect of the D1 agonist, SKF 38393, was studied in combination with intranigral infusions of glutamate antagonists of the NMDA (MK 801, CPP) or AMPA (NBQX) type of receptor. Local infusion into the SN of the 6-OHDA lesioned side of MK 801, CPP or NBQX at doses inducing no or minimal behavioral effects significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. The same result was obtained after intra-SN infusion of the GABA agonist, muscimol. High doses of MK 801, CPP or muscimol infused into the SN produced intense contralateral turning per se and induced a sparse c-fos expression in the lesioned CPu which was antagonized by parenteral administration of MK 801. The results indicate that a depression of SN pars reticulata efferent neurons potentiates D1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D1 receptor agonists. PMID- 7792719 TI - Effects of the sigma receptor ligand SR 31742A on neurotensin biosynthesis in rat basal ganglia. AB - The effects of SR 31742A, a specific sigma ligand, were investigated on neurotensin (NT) biosynthesis in the basal ganglia of the rat. Both single and repeated treatments with either SR 31742A (20 mg/kg i.p.) or haloperidol (1 mg/kg i.p.) increased the concentration of NT-like immunoreactivity (NT-li) in the nucleus accumbens. In contrast to haloperidol, the administration of SR 31742A failed to increase the concentration of NT-li in the caudate-putamen. We have further investigated drug-induced variations in NT biosynthesis by studying NT/neuromedin N (NT/NN) mRNA levels in the nucleus accumbens and the ventral tegmental area of the rat following SR 31742A administration. The NT/NN mRNA levels in the ventral tegmental area were increased by a maximum of fifteen fold (7 h at 20 mg/kg i.p.). A lower increase in NT/NN mRNA levels was elicited in the nucleus accumbens. These results suggest that the increase in NT-li observed after SR 31742A treatment, like that produced by haloperidol, may result from an increase of NT biosynthesis. Furthermore, the effects of SR 31742A on NT metabolism are similar to those of atypical antipsychotics, since they appear to be selective for the limbic system. PMID- 7792720 TI - Synaptic reorganisation in the rat striatum after dopaminergic deafferentation: an ultrastructural study using glutamate decarboxylase immunocytochemistry. AB - The ultrastructure of GABAergic and non-GABAergic synapses in the adult rat neostriatum was examined 6-8 months after unilateral removal of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine injection into the medial forebrain bundle. GABAergic profiles were identified by preembedding glutamate decarboxylase (GAD) immunocytochemistry performed on parasagittal vibratome sections. In three representative fields of the striatum, the nature and number of boutons and their postsynaptic partners were determined and the differences between the striata ipsi- and contralateral to the lesion analyzed. The percentage of GAD-immunoreactive boutons was increased from 23% on the intact side to 28% on the lesioned side. In addition, the GABAergic boutons underwent significantly more multiple contacts with several independent postsynaptic profiles, preferentially with dendritic spines. This could reflect a lesion induced sprouting of local GABAergic axon terminals. On the other hand, although the vast majority of GABAergic boutons underwent synaptic contacts with dendrites (77% vs. 80%), the number of boutons per dendrite or per dendritic circumference remained unchanged. Thus, the higher frequency of GABAergic boutons may simply reflect the loss of the dopaminergic nerve endings, without a heterosynaptic replacement by GABAergic boutons. The deafferentation also induced structural changes of the postsynaptic profiles. Some dendritic spines had a shortened neck; others were completely integrated in the dendrite which now contained a spine apparatus and was contacted by boutons with the features of axospinous synapses. The spine retraction resulted in a quantitative decrease in the number of spines. Analysis of the synaptic curvature revealed that only spines with a flat contact zone were lost. Concurrently, the number of dendrites was increased, of the GAD containing in particular, suggesting that the denrites of GABAergic interneurons tend to elongate and/or arborize. Taken together, the results of the present study show that the dopaminergic denervation caused a remodeling of the postsynaptic neurons. The relative increase of the number of GABAergic boutons and their synaptic contacts suggests that an altered wiring of the intrinsic GABAergic system contributes to the changes in the striatal output activity. PMID- 7792721 TI - Glutamate/dopamine D1/D2 balance in the basal ganglia and its relevance to Parkinson's disease. AB - The recent availability of selective ligands for NMDA and AMPA receptors has enabled neuroscientists to test the hypothesis that Parkinson's disease is a glutamate hyperactivity disorder and hence treatable with glutamate antagonists. This review takes a critical look at the motor characteristics of this new class of drugs in rodent and primate models of parkinsonism and assesses the clinical potential and pitfalls of this radical new approach. Monotherapy of Parkinson's disease with glutamate antagonists appears impractical at the present time, due to their low efficacy and unacceptable side effects, but polypharmacy with L-DOPA and a glutamate antagonist as adjuvant is a more realistic prospect. This review will focus on the ways in which glutamate receptor blockade facilitates motor recovery with L-DOPA and will examine whether the basis for this beneficial effect can be traced to a specific interaction with dopamine at D1 or D2 receptors, and therefore to discrete motor pathways within the basal ganglia. PMID- 7792722 TI - A new morphological feature associated with perforated synapses: vesicular lateralization. PMID- 7792724 TI - Trends in the health of older Americans: United States, 1994. Analytic and epidemiologic studies no. 3. PMID- 7792723 TI - Lipophilic metabolite of [123I]beta-CIT in human plasma may obstruct quantitation of the dopamine transporter. AB - I-123 or C-11 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta CIT) is a recently developed radioligand for the study of dopamine and serotonin reuptake sites in humans with single photon emission tomography (SPET) or positron emission tomography (PET). Determination of the radioligand metabolite pattern is fundamental for a quantitative analysis of radioligand binding. The metabolism of [123I]beta-CIT was determined by a gradient HPLC method in plasma samples of six human subjects. Two metabolites of [123I]beta-CIT were found, a polar and a lipophilic. At 4 h after [123I]beta-CIT injection the percentages of parent compound and polar and lipophilic metabolites were 23 +/- 3% (mean +/- SD), 33 +/- 11%, and 44 +/- 8%, respectively. The lipophilic metabolite might pass the blood-brain barrier and account for a fraction of free and nonspecifically bound radioactivity in brain. The existence of a lipophilic metabolite of [123I]beta-CIT may obstruct the use of simple ratio methods for quantitation of the dopamine transporter in brain. PMID- 7792725 TI - Systematic underestimation of treatment effects as a result of diagnostic test inaccuracy: implications for the interpretation and design of thromboprophylaxis trials. AB - Many clinical trials that have assessed strategies for the prevention of deep vein thrombosis have employed diagnostic tests that are less accurate than venography. The correct interpretation of these trials has been the subject of considerable debate. This paper attempts to quantify the likely effects of the use of inaccurate diagnostic tests (in particular fibrinogen scanning) on the validity and precision of estimates of treatment effects. It is shown that, if there is no difference in the rate of misclassification of deep vein thrombosis between study and control groups, then treatment effects will tend to be systematically underestimated in trials that only use inaccurate diagnostic tests. However, for trials in which there are no false positive diagnoses, such as those employing venography, the estimate of relative treatment effects will be unbiased. This phenomenon is demonstrated empirically by data from randomised trials of antiplatelet therapy. The implications of these findings are two-fold. First, so long as the accuracy of the test is the same in study and control groups, positive trial results cannot be ascribed to diagnostic test inaccuracy. Second, unbiased estimates of relative treatment effects can be obtained by using cheap, practicable and non-invasive screening tests that are supplemented by venographic assessment of positive test results. This would facilitate the conduct of much larger randomised trials than has generally been possible when mandatory venography was used; if future trials randomised some thousands of patients and employed confirmatory venography then they would provide both unbiased and precise estimates of relative treatment effects. PMID- 7792726 TI - The complexity of the phospholipid binding protein Annexin V. PMID- 7792727 TI - Urokinase therapy in neonates with catheter related central venous thrombosis. AB - The results of fibrinolytic therapy with urokinase were evaluated in 26 neonates with catheter related central venous thrombosis. Complete thrombolysis could be achieved in 13 patients (50%), partial thrombolysis in 3 patients (12%). No effect was seen in 10 patients (38%). Therapy success was influenced by age, size and location of the thrombus. Coincidence of infection occurred in 16 patients (62%). Mild hemorrhagic complications were seen in 2 patients (8%), no other significant side effects were observed. Nine patients with residual thrombosis were treated with oral anticoagulants following urokinase resulting in resolution of the thrombus in 6 patients within 3 months (67%). The incidence of asymptomatic recurrent thrombosis was high (28%). Urokinase might be an effective and safe treatment for central venous thrombosis in neonates. Prophylactic antibiotic therapy during the infusion of urokinase and long-term treatment with oral anticoagulants after thrombosis are advisable. Early detection of thrombosis might enhance the success rate of fibrinolytic therapy. Therefore, we strongly recommend routine echocardiographic screening of central venous catheters. PMID- 7792728 TI - Six different point mutations in seven Danish families with symptomatic protein C deficiency. AB - Six different point mutations of the protein C gene are described in seven Danish families with protein C deficiency associated with an increased risk of venous thromboembolism. All affected family members are heterozygotes for the mutated protein C genotype. One mutation is a G2992-->A transition at position +5 in the 5' splice site of intron D. The other five mutations affect the protein coding region. One is a C1432-->T transition in exon III converting the highly conserved Arg15 to Trp in the Gla-domain. Another mutation is a G3157-->C transversion in exon V converting the non-conserved Gly72 to Arg in the epidermal growth factor domain. The remaining three mutations are located in non-conserved amino acid positions in exon IX and affect the serine proteinase domain. The first is a G8559-->C transversion converting Gly282 to Arg. The second is a C8571-->T transition (present in two families) converting Arg286 to Cys. The third is a C8695-->T transition converting Pro327 to Leu. In each family the protein C deficiency cosegregates or probably cosegregates (one family, G8559-->C) with the mutation. All affected family members exhibit a reduction of both the antigen and the functional plasma concentration of protein C to approximately 50% of normal indicating that the mutated protein C is not present (type 1 deficiency) or only present in low amounts in plasma. Agarose gel electrophoresis followed by Western blotting shows that the Arg15-->Trp substitution is associated with a normal as well as an abnormal migrating plasma protein C band.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792729 TI - Definition of the bleeding tendency in factor XI-deficient kindreds--a clinical and laboratory study. AB - Individuals with severe factor XI deficiency are prone to excessive bleeding after injury or surgery, but the existence of a haemorrhagic tendency in partial factor XI deficiency is controversial. In this study, 172 members of 30 kindreds (20 non-Jewish) transmitting factor XI deficiency in North West England were interviewed and a bleeding history questionnaire completed. Blood was taken for coagulation assays. The questionnaires were categorised independently by two assessors to determine presence or absence of a bleeding tendency, in the absence of information about the factor XI level or family history. Analysis shows that 48% of heterozygotes have a bleeding tendency. Eighteen (60%) families came to attention because of bleeding problems in heterozygotes. Comparison of histories between partially deficient and non-deficient individuals demonstrated a higher incidence of menstrual problems, an increase in significant bruising, and an increased likelihood of excessive bleeding after tonsillectomy and dental extractions. The incidence of von Willebrand's disease was not increased, but individuals with heterozygous factor XI deficiency who were bleeders tended to have lower levels of factor VIIIc and von Willebrand factor, and were more commonly of blood group 0. These features may contribute to the bleeding tendency. There was no evidence of alteration in factor VII activity (as defined by the ratio of activity to antigen) between the bleeders and non-bleeders. This is convincing evidence for abnormal bleeding in factor XI deficiency which is not confined to severely deficient patients. PMID- 7792730 TI - Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala. AB - We have identified a patient with a dysfunctional prothrombin that we have designated Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level of 13% and 20% compared to normal controls using two different assays with a normal prothrombin antigen level of 91% of normal controls. The genetic defect responsible for the abnormal prothrombin activity was determined by the polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) analysis and by DNA sequence analysis of the human prothrombin gene. Substitution of a C for an A at nucleotide 10177 in the human prothrombin gene of the proband was identified, which results in the replacement of Glu-466 by Ala. The proband and one sister were homozygous for this mutation. Both parents, as well as one brother, were found to be heterozygous for this mutation. The same amino acid substitution was previously identified to be responsible for the dysfunctional protein Prothrombin Salakta and was hypothesized to result in altered substrate specificity. Four polymorphisms were also identified in the prothrombin gene from the proband when compared to the published sequence at nucleotides 554, 4048, 4272 and 10253. PMID- 7792731 TI - Platelet consumption in thrombocythemia complicated by erythromelalgia: reversal by aspirin. AB - The involvement of platelets in the pathogenesis of erythromelalgia, a frequent and characteristic microvascular thrombotic manifestation in patients with primary thrombocythemia and polycythemia rubra vera, was investigated by measuring the survival and turnover of 51Cr labeled autologous platelets in 10 patients with thrombocythemia complicated by erythromelalgia, in 10 asymptomatic thrombocythemia patients and in 6 subjects with reactive thrombocytosis. The mean platelet survival time of the erythromelalgia patients was 4.2 +/- 0.2 days, which is significantly decreased as compared with asymptomatic thrombocythemia patients (6.6 +/- 0.3 days, p < 0.001) and patients with reactive thrombocytosis (8.0 +/- 0.4 days, p < 0.001). The mean platelet survival time of asymptomatic thrombocythemia patients was significantly decreased (p < 0.01) as compared with reactive thrombocytosis patients. Treatment of erythromelalgia with aspirin increased the mean platelet survival time from 4.0 +/- 0.3 days to 6.9 +/- 0.4 days (p < 0.001) and was associated with an elevation of the platelet count of 216 +/- 30 x 10(9) platelets per liter (p < 0.001). Coumadin failed to improve platelet survival or symptoms caused by erythromelalgia. The increased platelet consumption in erythromelalgia is attributed to the formation of platelet thrombi in the arterial microvasculature. This conclusion is supported by the ability of aspirin to interrupt platelet consumption and clinical features of erythromelalgia. PMID- 7792732 TI - Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. AB - The incidence of factor VIII inhibitor was studied in a cohort of 56 previously untreated patients with severe hemophilia A (factor VIII below 1 U/dl). They received only one brand of highly purified factor VIII concentrate (HPSD-VIII) prepared by conventional chromatography with a solvent-detergent step for viral inactivation. Follow-up since the first infusion of HPSD-VIII was from 1 to 76 months (mean = 29) and cumulative exposure days (CED) from 1 to over 100 (median = 26). Five patients (9%) developed an inhibitor after 6 to 19 CED, only one being a high responder (2%), showing a low incidence of inhibitor compared with previous studies using high purity plasma-derived or recombinant products. PMID- 7792733 TI - Effects of two different doses of hirudin on APTT, determined with eight different reagents. AB - The APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study. Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica based reagents. In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica-containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model. PMID- 7792734 TI - Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa. AB - Gram-negative sepsis is oftentimes complicated by activation of coagulation with disseminated intravascular coagulation and microthrombosis. This may contribute to the associated morbidity, multiple organ failure and death. Recent studies have established that the tissue factor-dependent pathway of blood coagulation has a significant participatory role in the initial endotoxin-induced activation of coagulation. Tissue factor (TF), expressed on the surface of activated monocytes and endothelial cells forms cell surface complexes with free circulating factors VII and VIIa. The latter complex proteolytically activates factors X and IX. Recent in vivo experiments have shown that a rapidly neutralizing TF monoclonal antibody prevents and arrests the endotoxin-induced activation of coagulation and similar studies have shown to reduce mortality in baboons. In this study we describe the preparation of a factor VII/VIIa neutralizing monoclonal Fab fragment and characterize its effect on in vivo activation of coagulation during experimental endotoxemia in chimpanzees. Four chimpanzees received a bolus intravenous injection of 4 ng/kg endotoxin in combination with Fab fragments of a factor VII/VIIa neutralizing murine monoclonal antibody (12D10) at a dose of either 50 micrograms/kg (n = 2) or 100 micrograms/kg (n = 2). Four control animals received a bolus injection of endotoxin alone. Administration of the 12D10 Fab fragments, immediately preceding the endotoxin bolus injection, effectively blocked the endotoxin-induced activation of coagulation. Plasma levels of products of in vivo activation, namely F1 + 2, TAT complexes and FpA remained at baseline values. The administration of 12D10 resulted in a rapid decline in factor VII/VIIa antigen levels which remained below 5 ng/ml for 180-240 min, followed by a rapid return to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792735 TI - Internalization and degradation of recombinant human coagulation factor VIIa by the human hepatoma cell line HuH7. AB - Previous studies demonstrated that several normal and transformed cultured human cell lines specifically bind human coagulation factors VII and VIIa via tissue factor. In the present study, we show that 125I-radiolabeled recombinant human factor VIIa (125I-rFVIIa) binds to a human hepatoma cell line (HuH7). In the presence of rabbit polyclonal anti-human tissue factor apoprotein IgG, binding of 125I-rFVIIa to the HuH7 cells was decreased approximately 60%, suggesting of tissue factor-independent binding sites for 125I-rFVIIa on these cells. The binding isotherm of 125I-rFVIIa for the HuH7 cells in the presence of anti-tissue factor IgG exhibited a hyperbolic profile and was time-, temperature- and calcium dependent. Furthermore, binding at 4 degrees C was specific, dose-dependent and saturable. Scatchard analysis of the binding data demonstrated a single class of binding sites with a dissociation constant (Kd) of 3.2 nM and 27,000 binding sites per cell. At 4 degrees C, 125I-rFVIIa bound to, and eluted from, the cell was indistinguishable from offered 125I-rFVIIa as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. The molecular properties of the tissue factor-independent binding protein were studied by using the cleavable cross-linking agent 3,3' dithiobis(sulfosuccinimidylpropionate). A cross-linking product of 125I-rFVIIa and a cell surface protein with an apparent M(r) approximately 100,000 was observed. The cross-linking reaction was strongly inhibited by a 100-fold molar excess of unlabeled rFVIIa, but not by rabbit polyclonal anti-human tissue factor apoprotein IgG, indicating that cross-linking does not involve the extracellular domain of tissue factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792736 TI - Dietary changes in fasting levels of factor VII coagulant activity (FVII:C) are accompanied by changes in factor VII protein and other vitamin K-dependent proteins. AB - The mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII:C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1 + 2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied by a decrease in FVII protein, F1 + 2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII:Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part of a general change in concentrations of vitamin K-dependent proteins. PMID- 7792737 TI - The effect of insulin-induced hypoglycaemia on factor VIII:C concentrations and thrombin activity in subjects with type 1 (insulin-dependent) diabetes. AB - The effect of insulin-induced hypoglycaemia on plasma coagulant activity was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a computer ex-vivo assisted chromogenic method and by the activated partial thromboplastin time (APTT). In addition, factor VIII:C, thrombin-antithrombin III (TAT) complex and fibrinopeptide A (FPA) levels were measured. Hypoglycaemia induced a rise in mean (SD) factor VIII:C concentrations from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after onset of symptoms and they remained increased at 90 min [1.54 (0.57) and 1.5 (0.54) IU/ml, p < 0.001 respectively]. A corresponding reduction in time to generate 50% maximal thrombin activity occurred from a pre-insulin value of 56 (6) s to a minimum reading of 46 (7) s at 15 min (p < 0.001) and remained low at 90 min [48 (6) s, p < 0.001]. APTT shortened from 43.3 (4.8) s to 40.1 (4.6) s at 30 min (p < 0.001) but did not fall below the normal range (37.6 42.7 s) and no significant changes in TAT or FPA levels were noted. Factor VIII:C correlated inversely with time to generate 50% maximal thrombin activity and APTT (r = -0.580, p < 0.001; r = -0.673, p < 0.001, n = 66, respectively). The results show that the rise in plasma factor VIII:C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in contact-activated plasma, though concentrations of FPA and TAT remain unchanged, although TAT complexes are not a sensitive marker of in vivo thrombin generation. PMID- 7792738 TI - The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. AB - Antibodies against factor VIII coagulant activity can appear in haemophiliacs who are treated with factor VIII preparations but also spontaneously in non haemophiliacs. The Bethesda assay is the most commonly used method to detect these antibodies, but it lacks specificity especially in the lower range resulting in unreliable data. Two modifications are proposed and tested to resolve the imperfections: 1. Buffering the normal plasma used in the assay- and control mixture with 0.1 M imidazole to pH 7.4. 2. Replacing the imidazole buffer in the control mixture by immunodepleted factor VIII deficient plasma. These modifications allow better discrimination between positive and negative samples and improve reliability. PMID- 7792739 TI - Antinociceptive properties of protein C in a model of inflammatory hyperalgesia in rats. AB - We investigated the role of human protein C in an animal model of inflammatory hyperalgesia. Pain was induced by intraplantar injection of carrageenan (3 mg) into the hind paw of rats. The pain threshold was measured by exerting increasing amounts of pressure (in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg) was administered intravenously immediately after carrageenan. Controls received either intraplantar injections of saline (100 microliters) instead of carrageenan or carrageenan alone. Effects on pain threshold were expressed in percent of the pretreatment value. Carrageenan alone lowered the mean pain threshold after 3 h to 33.2 +/- 2.2% of the pretreatment level. Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with saline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinociceptive effect. Protein C had no effect in animals not preconditioned with intraplantar carrageenan. Thus protein C clearly antagonized the inflammatory pain induced by carrageenan. The antinociceptive action of protein C was antagonized by injection of a monoclonal antibody against protein C, providing additional evidence that the effect was protein C-mediated. PMID- 7792740 TI - ARIC hemostasis study--IV. Intraindividual variability and reliability of hemostatic factors. The Atherosclerosis Risk in Communities (ARIC). AB - We have recently reported the short-term intraindividual variability of several coagulation factors and inhibitors included in the ARIC study (Chambless et al. Ann Epidemiol 1992; 2:723). In this paper, we reported the intraindividual variability results of additional hemostatic factors. Blood samples were collected for hemostatic assays three times at 1-2-week intervals from 39 subjects recruited from 4 ARIC field centers. The contributions of within-person, processing and assay (designated "method") and between-person variances to the total variance were estimated and from them the reliability coefficient, R, was computed as the proportion of total variance in the between-person component. The R value was high for beta-thromboglobulin and tissue-plasminogen activator: 0.83 and 0.81, respectively; and intermediate for D-dimer and plasminogen activator inhibitor-1: 0.73 and 0.72, respectively. Protein S (total and free) and platelet factor 4 had low repeatability (R < 0.50) derived mostly from "method" variability while low R value (0.03) for fibrinopeptide A was attributed to high "method" and "within-person" variability. Gender, age and the level of hemostatic factors did not influence the intraindividual variability. PMID- 7792741 TI - Determinants of plasminogen activator inhibitor-1 activity in survivors of myocardial infarction. AB - A significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immunoenzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs = 0.43; p < 0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p < 0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p < 0.0001) and des-31,32-proinsulin (rs = 0.54; p < 0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction. PMID- 7792742 TI - Up-regulated expression of plasminogen activator inhibitor-1 in Hep G2 cells: interrelationship between insulin and insulin-like growth factor 1. AB - Insulin resistance represents a situation with a high risk of atherothrombosis and is accompanied by increased plasma plasminogen activator inhibitor-1 (PAI-1) levels. Fasting insulin level is highly correlated with PAI-1 levels in plasma. It has been shown that insulin increases PAI-1 synthesis by the human hepatoma cell line Hep G2. Moreover when Hep G2 cells expressing a down-regulation of insulin receptors by incubation with 10(-7) M insulin, were stimulated by 10(-9) M insulin, an overexpression of PAI-1 synthesis was observed despite a reduced number of insulin receptors. Insulin-like growth factor 1 (IGF-1) shares many properties with insulin. The aim of the present study was to evaluate the effect of IGF-1 on PAI-1 synthesis by Hep G2 cells down-regulated either by insulin or IGF-1. Incubation of Hep G2 cells with increasing doses from 10(-9) to 10(-7) M IGF-1 induced a dose-dependent stimulation of PAI-1 synthesis up to 4.5-fold the control level. When cells were first pre-incubated with 10(-7) M IGF-1 for 18 h, acid washed, and then stimulated with 10(-9) M IGF-1, the expression of IGF-1 receptors was greatly reduced (up to 70%). In contrast PAI-1 secretion was increased 3.4-fold the level of control cells and by 1.9-fold the level of cells first stimulated with 10(-9) M IGF-1. Both transcripts of PAI-1 mRNA were also increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792744 TI - Acute dynamic exercise increases fibrinolytic activity. AB - The influence of acute bouts of dynamic exercise on plasma tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and fibrinogen was investigated on nine healthy non-smoking men aged 23 to 37 years. Subjects performed maximal and two submaximal (duration 30 min, intensity 50% [aerobic threshold] and 78% [anaerobic threshold]VO2max) bicycle ergospirometry tests separated by seven days. The order of the submaximal tests was randomized. Blood samples were drawn before, immediately after and 24 h after each test. Plasma tPA and PAI activities were measured amidolytically, and fibrinogen concentration by thrombin method. All postexercise values were corrected for the change in plasma volume. The pre-exercise tPA and PAI activities and fibrinogen concentration were similar in each tests. tPA activity increased during each test (from 2.0 [SEM 0.24] IU/ml to 20.3 [3.14] during maximal, 2.0 [0.22] to 19.0 [2.59] during anaerobic threshold test, 1.8 [0.22] to 5.5 [0.82] during aerobic threshold; p < 0.001 during all tests, p = 0.01 aerobic threshold vs maximal and anaerobic threshold). PAI activity decreased during maximal (from 6.6 [2.51] AU/ml to 2.0 [2.00], p < 0.05) and anaerobic threshold (5.0 [2.07] to 0.2 [0.22], p < 0.01) tests but not during aerobic threshold test (7.0 [3.69] to 4.5 [2.93], p = 0.123). One subject had clearly higher pre-exercise PAI activity and smaller tPA response to exercise as compared to other subjects. All 24 h post-exercise activities were similar to pre-exercise values. Plasma fibrinogen concentration did not change during any tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792743 TI - Limited proteolysis of human alpha-thrombin by urokinase yields a non-clotting enzyme. AB - Limited proteolysis of human alpha-thrombin by various proteases has been efficiently used to demonstrate the importance of two insertion loops located on the surface of this molecule. In the present study, we demonstrate that two-chain urokinase (tcu-PA) specifically cleaves the B chain of alpha-thrombin giving rise to a transient derivative, consisting of two non-covalently linked subunits. Although the thrombin derivative conserves its activity towards the synthetic substrate S-2238 (Km = 8.4 microM and kcat = 145 s-1 versus respectively 4.5 microM and 149 s-1 for alpha-thrombin), most of its coagulant activity is lost (140 NIH u/mg versus 3000 NIH u/mg) and its ability to activate platelets is considerably reduced (threshold for full platelet aggregation 2.5 nM versus 0.25 nM). The thrombin fragments were separated by HPLC and after reduction and S carboxyamidemethylation were digested with a lysylendopeptidase; the resulting peptides were separated by HPLC and sequenced. One fragment corresponded to B chain fragment 1-73 and the second to B chain fragment 74-259 covalently linked to the A chain, indicating that tcu-PA cleaves selectively the peptide bond Arg 73-Asn 74 in the B chain. The proteolytic derivative obtained, designated beta u thrombin, is therefore identical to the transient proteolytic derivative, beta 1 thrombin, produced by trypsin. Prolonged incubation with tcu-PA resulted in further conversion in a derivative analogous to gamma t-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792746 TI - Internalization of an anti-glycoprotein IIb/IIIa antibody by HEL cells. AB - Platelets are known to internalize monoclonal antibodies directed against the glycoprotein (GP) IIb/IIIa complex. We investigated whether an antibody directed against this complex (NNKY 2-11) was transported from the surface membrane to the intracellular pool in HEL cells. Flow cytometry showed that the percent binding of NNKY 2-11 to the surface membrane of HEL cells was decreased after incubation for 24 h compared with 1 h, while the binding of an anti-GPIb antibody (NNKY 5-5) did not change. It did not seem likely that the GP IIb/IIIa complex antibody was shed from the surface membrane of the HEL cells during incubation, because the medium conditioned by incubation with these cells for 24 h showed almost no binding to washed platelets. In addition, immunoelectron microscopy demonstrated that GP IIb/IIIa complex antibodies were incorporated into the intracellular pool of HEL cells and were associated with alpha granules. These findings indicated that an anti-GP IIb/IIIa antibody could be internalized by megakaryocytes, as has been previously shown with platelets, suggesting that megakaryocyte GP IIb/IIIa may act as a carrier for various adhesion proteins. PMID- 7792745 TI - Desmin 370, a low molecular weight dermatan sulfate, reduces the weight of preformed thrombi in rats made afibrinogenemic by ancrod. AB - Desmin 370 (D370), a low molecular weight dermatan sulfate, has been shown to induce a marked reduction of the weight of preformed venous thrombi in rats and rabbits by mechanisms that appeared largely independent of inhibition of thrombus accretion. In order to provide further support for such a mechanism, we exploited the defibrinating capacity of ancrod to obtain a thrombosis model characterized by the lack of thrombus growth and thus sensitive only to agents promoting thrombus lysis. Thrombus formation in anesthetized rats was induced by vena cava ligature. Injection of ancrod (5 U/kg) 5 h after induction of venous stasis caused a more than 95% reduction in plasma fibrinogen and prevented thrombus accretion as indicated by the lack of thrombus weight increase during the 3 h experimental period (12.2 +/- 0.6 vs 14.5 +/- 1 as compared to 12.6 +/- 0.6 vs 19.6 +/- 0.8, p < 0.01, in control rats) and by the almost complete (> 90%) inhibition of 125I-fibrin(ogen) binding to thrombi. Moreover, when ancrod was given 1 h before vena cava ligature, no thrombi were formed within 2 h whereas at the same time interval visible thrombi were present in all control rats. Administration of D370 (10 mg/kg) to thrombus bearing rats, 1 h after induction of afibrinogenemia, resulted in a significant reduction in thrombus weight (43% after 2 h, p < 0.01) which was only slightly lower than that recorded in normofibrinogenemic rats (54%). Enhancement of plasma fibrinolytic activity by ancrod had no influence on thrombus lysis and was not all affected by administration of D370.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792747 TI - Fibrinogen binding is independent of an increase in intracellular calcium concentration in thrombin degranulated platelets. AB - In a suspension of thrombin degranulated platelets (TDP), ADP and epinephrine can induce platelet aggregation, whereas the synthetic agonist of the thromboxane/endoperoxide receptor U46619 causes only shape change. However, U46619 can enhance platelet aggregation induced by ADP and epinephrine. In this paper, we have measured fibrinogen binding in relation to phospholipase C (PLC) activation and calcium mobilization in TDP activates by ADP, epinephrine and U46619. ADP caused fibrinogen binding in TDP but neither activated PLC nor caused a calcium mobilization. The requirement for ADP in inducing exposure of fibrinogen binding sites was not absolute since the combination of epinephrine and U46619 produced an increase in fibrinogen binding. U46619 caused significant PLC activation and cytosolic calcium release but not fibrinogen binding. These results suggest that in TDP the exposure of fibrinogen binding sites, after agonist activation, is independent of both PLC activation and calcium mobilization. PMID- 7792749 TI - Antithrombotic effect of a recombinant von Willebrand factor, VCL, on nitrogen laser-induced thrombus formation in guinea pig mesenteric arteries. AB - To assess the antithrombotic effectiveness of blocking the platelet glycoprotein (GP) Ib/IX receptor for von Willebrand factor (vWF), the antiaggregating and antithrombotic effects were studied in guinea pigs using a recombinant fragment of vWF, Leu 504-Lys 728 with a single intrachain disulfide bond linking residues Cys 509-Cys 695. The inhibitory effect of this peptide, named VCL, was tested in vitro on ristocetin- and botrocetin-induced platelet aggregation and compared to the ADP-induced platelet aggregation. In vivo, the antithrombotic effect of VCL was tested in a model of laser-injured mesentery small arteries and correlated to the ex vivo ristocetin-induced platelet aggregation. In this model of laser induced thrombus formation, five mesenteric arteries were studied in each animal, and the number of recurrent thrombi during 15 min, the time to visualization and time to formation of first thrombus were recorded. In vitro, VCL totally abolished ristocetin- and botrocetin-induced platelet aggregation, but had no effect on ADP-induced platelet aggregation. Ex vivo, VCL (0.5 to 2 mg/kg) administered as a bolus i.v. injection inhibits risocetin-induced platelet aggregation with a duration of action exceeding 1 h. The maximum inhibition was observed 5 min after injection of VCL and was dose related. The same doses of VCL had no significant effect on platelet count and bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792750 TI - Very low frequency of "normandy type" mutations among type 1 von Willebrand disease families. PMID- 7792748 TI - Glycoprotein Ib can mediate endothelial cell attachment to a von Willebrand factor substratum. AB - Introduction of single amino acid substitutions into the C-terminal Arg-Gly-Asp Ser (RGDS) site of von Willebrand Factor, referred to as RGD mutant vWF, selectively abrogated vWF binding to platelet glycoprotein IIb/IIIa (GpIIb/IIIa alpha IIb beta 3) and abolished human umbilical vein endothelial cell (HUVEC) spreading, but not attachment, to RGD mutant vWF (Beacham, D.A., Wise, R.J., Turci, S.M. and Handin, R. I. 1992. J. Biol. Chem. 167, 3409-3415). These results suggested that in addition to the vitronectin receptor (VNR, alpha V beta 3), a second endothelial membrane glycoprotein can mediate HUVEC adhesion to vWF. HUVEC attachment to wild-type (WT) and RGD-mutant vWF was reduced by two proteins known to block the vWF-platelet glycoprotein Ib/IX (GpIb/IX) interaction, the monoclonal antibody AS-7 and the recombinant polypeptide, vWF-A1. The addition of cytochalasin B or DNase I to disrupt potential GPIb alpha-cytoskeletal interactions enhanced the immunoprecipitation of endothelial GPIB alpha, caused HUVEC to round up, and increased HUVEC adhesion to RGD mutant vWF. These results indicate that while the VNR is the primary adhesion receptor for vWF, endothelial GPIb alpha can mediate HUVEC attachment to vWF. GpIb-dependent attachment could contribute to HUVEC adhesion under conditions when cell surface expression of the VNR is downregulated, and VNR-dependent adhesion is reduced. PMID- 7792751 TI - Effect of factor VII genotype on response to warfarin treatment. PMID- 7792752 TI - Plasma thrombomodulin is increased in cord blood of healthy newborns. PMID- 7792753 TI - Acquired factor VIII inhibitor associated with a prostatic cancer: simultaneous occurrence and healing. PMID- 7792754 TI - Loss of heparin-releasable tissue factor pathway inhibitor in patients undergoing PTCA. PMID- 7792755 TI - Comparison of HLA-DRB1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation. AB - The aim of the study was to devise a strategy for large batch analysis to determine HLA Class II alleles exhibited by candidate bone marrow transplant donors and prospective recipients using previously published DNA-based typing techniques. Special attention was directed towards the technical aspects of procedures, the level of typing resolution and the speed of data analysis. 200 blood samples from volunteer bone marrow transplant donors typed serologically for HLA-DR and DQ were further investigated using three DNA-based typing methods: (i) restriction fragment length polymorphism (RFLP) analysis, (ii) polymerase chain reaction (PCR) amplification and subsequent hybridisation with sequence specific oligonucleotide probes (PCR-SSO), and (iii) PCR amplification with sequence specific primers (PCR-SSP) to resolve the DRB1* specificity of each individual. In general, the HLA-DR results obtained using PCR-SSO and PCR-SSP correlated well with each other. However, discordant results were obtained between PCR and RFLP based typing in 21 cases, especially in relation to DRB3* alleles associated with the DRB1 gene. These differences were due to three problems pertaining to RFLP analysis: i) alleles with identical DRB, DQA and DQB fragment sizes, ii) reliance on DQA and DQB results to assign the DRB genotype, and iii) a "new polymorphism" of DR7, in a DR7 homozygous, exhibiting a fragment similar in size to DR8. Our findings suggested a strategy requiring PCR-SSO analysis for initial low resolution class II typing involving large numbers of samples, while the use of PCR-SSP is reserved for small numbers of samples, for urgent samples or for situations where higher resolution is required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792756 TI - Distribution of HLA and haplotypes of Colombian and Jamaican black populations. AB - To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to the Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three locus HLA haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians, while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaican were originated from African blacks and admixed variably with Caucasians and South American Indians to make genetic subpopulations in Colombia and Jamaica. PMID- 7792758 TI - HLA-DRB1*01 subtyping by heteroduplex analysis. AB - In this report we describe an alternative method for the identification of the four known HLA-DRB1*01 alleles, which is based on the generation of unique heteroduplex patterns between the different DRB*01 alleles and a synthetic DNA heteroduplex generator (DHG) molecule. The method is technically simple, rapid and cost-effective, as it essentially involves only a single polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. This technique allows the rapid discrimination of the various known HLA-DRB1*01 subtypes, both in homozygous and heterozygous situations. We propose that this technology can potentially be applied to most HLA class I and class II subtyping. PMID- 7792757 TI - HLA in familial and nonfamilial Mediterranean Kaposi's sarcoma in Greece. AB - Fifty-four (54) unrelated patients with Mediterranean Kaposi's sarcoma (MKS) and 8 patients members of 4 unrelated families with familial MKS were serotyped for HLA-A,B and DR antigens. The diagnosis was histologically confirmed and all patients were negative for anti-HIV antibodies. An increased frequency of HLA-B18 (44.4% vs 14.2% in the controls, p < 0.001, RR = 4.8) and HLA-DR5 (57.6% vs 37.2% in the controls, p < 0.025, RR = 2.29) was observed in the group of patients with MKS. Seven (7) of the 8 family members with FMKS possessed HLA-DR5, and the affected members in the 3 families shared a common haplotype which included HLA DR5. These findings support the hypothesis that genetic factors linked to HLA-DR5 antigen may contribute to the pathogenesis of MKS. PMID- 7792759 TI - A description of a new DR allele, DRB1*1113. AB - We have discovered a previously unpublished HLA-DRB1 allele, observed in a patient (SB), his mother, and one sibling. The undefined allele gave sporadic positive reactions with sera in the DR52-associated group. SSOPH analysis utilizing both generic and group specific primers and probes also gave ambiguous results. SB typed clearly as a DRB1*0301 (paternal allele) but the DNA from SB also bound probes specific for DRB1*14 and DRB1*11. Sequencing revealed that the undefined allele was similar to a DRB1*14 allele with a segment of sequence found in DRB1*11 alleles. The patient was MLC reactive with donors who express DRB1*0301, *1401 and *0301, *11 and was nonreactive solely to DRB1*0301 (Dw3) homozygous typing cells. PMID- 7792761 TI - Novel human TAP2*103 allele shows further polymorphism in the ATP-binding domain. PMID- 7792760 TI - Comparison of two HLA-DRB high resolution microtiter plate reverse hybridization typing methods: advantage of a codon-86 valine or glycine PCR segregation. AB - Two rapid, nonisotopic, high-resolution HLA-DRB typing methods have been developed for DRB1, DRB3, DRB4 and DRB5 alleles. These methods are based on a single procedure consisting of the reverse hybridization of biotinylated amplicons to oligonucleotide probes that are covalently attached to a microtiter plate. Detection is by an enzymatic reaction with a fluorescent substrate. The 1 Generic Amplification (1GA) method amplifies all HLA-DRB alleles in the same reaction mix. The 2 Allelic Subset Amplification (2SA) method uses two distinct amplification reactions that distributes all DRB alleles into two equal-size subsets, according to the codon 86 Gly or Val polymorphism; this adds an extra discrimination level to the typing. 108 samples were typed using the 1GA and the 2SA methods and no discrepancies were found. Typing indeterminations due to overlapping probe combinations were compared; it was found that the 2SA method, with the extra discrimination level at the PCR step, greatly improved resolution. PMID- 7792762 TI - An HLA-DR11 variant (HLA-DRB1*1115) segregating in a family of Turkish origin. PMID- 7792763 TI - HLA-DQ alleles and susceptibility to celiac disease in Spanish children. PMID- 7792765 TI - Comprehensive, serologically equivalent DNA typing for HLA-B by PCR using sequence-specific primers (PCR-SSP). AB - Polymorphic products of HLA class I genes from the human major histocompatibility complex (MHC) are traditionally assigned by serology with additional heterogeneity detectable using one-dimensional isoelectric focusing (1D-IEF). With the increased availability of HLA class I DNA sequence information it has become feasible to genotype for class I by polymerase chain reaction utilising sequence-specific primers (PCR-SSP). We describe here a comprehensive HLA-B PCR SSP typing system based on available HLA nucleotide sequences which can detect all serologically defined antigens in most heterozygous combination in 48 one step PCR reactions. In addition, four new unsequenced variants have been identified. DNA samples from 57 International Histocompatibility Workshop reference cell lines and 160 control individuals have been typed by the HLA-B PCR SSP technique. 3/57 cell line types and 12/160 normal control individuals types were discrepant with the reported serological types. The SSP system has been designed to be higher resolution than serology but is not a complete allele specific PCR although many single alleles can be identified. The system is entirely complementary to previous published PCR-SSP systems for HLA-Class II and HLA-Class I in that the same PCR conditions and controls are used which allows us to do one step PCR-SSP for all relevant HLA loci in under 3 hours in a system suitable for the typing of cadaver donors. PMID- 7792764 TI - Effects of the second HLA-DQ haplotype on the association with childhood insulin dependent diabetes mellitus. AB - Analysis of HLA-DQ molecules in a large study comprising 425 consecutively diagnosed Swedish Caucasians with IDDM and 367 age, sex and geographically matched controls confirms previous observations that: (a) DQB1*0302-DQA1*0301 confer susceptibility in a dominant manner, except when they are associated with DQB1*0602-DQA1*0102; (b) DQB1*0501-DQA1*0201 does not confer susceptibility to IDDM in either homozygous or heterozygous combinations with any other DQ molecules except when it is in association with DQB1*0302-DQA1*0301; (c) heterozygous combinations of DQB1*0302-DQA1*0301 and DQB1*0501-DQA1*0201 confer the highest risk to IDDM; (d) in DQ2 positive patients being negative for DQ8 in second haplotype (n = 58) the susceptibility may be explained by DR, since all these patients were DR3 positive, or by unknown factors between DQ and DR and (e) DQB1*0602-DQA1*0102 confers protection in a dominant manner. This large study does not confirm the positive association previously observed in Norwegians between the DQ8/DQ4 genotype and IDDM, as this genotype was not significantly associated with IDDM in Swedish patients. The new findings in this study include (a) that DQ8/DQ6 (DQB1*0604-DQA1*0102) was associated with IDDM in Swedish patients and (b) analysis of individual amino acids in DQB1 chain does not fully explain susceptibility to IDDM. PMID- 7792767 TI - Distribution of HLA antigens and haplotypes in the Buryat population of Siberia. AB - Polymorphisms of HLA-A, B, C, DR, and DQ antigens were investigated in a Mongoloid population named Buryat living in Siberia. HLA gene and haplotype frequencies were calculated from the population data obtained from 141 unrelated healthy Buryat adults. Gene frequencies of class I antigens A2, A24, A1, B61, Cw10, and Cw6 were estimated to be more than 10%. For class II, DR4, DR7, DR13, DQ7, and DQ1 antigens were predominant. A phylogenetic tree was constructed based on HLA gene frequencies, and the Buryat population was clustered with the Mongoloid groups in Northeast Asia. In the analysis of HLA-A, C, B, DR, and DQ five-locus haplotype frequencies, seven kinds of haplotypes were calculated to occur at frequencies of more than 2%. Five of the seven common haplotypes have also been described in the other human populations thus far. Some of the haplotypes have been described in European populations, while the others were shared with Northeast Asian Mongoloids as well as Amerindians. Similar situation was also found in the analysis of class I (HLA-A, C, B) three locus haplotypes. These observations suggest the unique genetic background of this Buryat population. PMID- 7792766 TI - Major histocompatibility complex class II and C4 alleles in Mexican Americans with systemic lupus erythematosus. AB - Few data exist on associations of class II and class III alleles of the major histocompatibility complex (MHC) and susceptibility to systemic lupus erythematosus (SLE) in Mexican Americans, a group of predominantly mixed Spanish and Native American ancestry. Therefore, MHC class II alleles (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1 alleles) and C4 allotypes were determined in 52 Mexican American SLE patients and 105 ethnic-matched controls. HLA-DRB1*0301 and C4A*Q0 were each increased in the SLE patients, especially HLA-DRB1*0301 in those with anti-Ro/SSA autoantibodies. C4A*Q0 was associated with HLA-DRB1*0301 only in a minority of patients and controls. Anti-U1RNP antibodies were significantly associated with the presence of HLA-DQB1*0302, and the risk for the production of anti-Ro antibodies was heightened by the presence of at least three (out of four possible) DQA1 chains possessing a glutamine at position 34 and/or DQB1 chains a leucine at position 26 of their outermost domains. Thus the HLA class II and C4 null allele associations that have been noted in other ethnic groups are also found in Mexican Americans, suggesting shared susceptibility factors across ethnic lines in predisposition to SLE. PMID- 7792768 TI - [Non-invasive patient monitoring in veterinary medicine: pulse oximetry and capnography. II. Capnography]. AB - Capnography measures carbon dioxide concentration or partial pressure of the respiratory gas continuously and non-invasively. The endtidal value is of great diagnostic value, it corresponds approximately to the arterial value, except for ventilation-perfusion-mismatching (horse), shunting (horse), or increased dead space-ventilation (panting in the dog). Capnography primarily serves for monitoring of spontaneous and artificial ventilation, it is a reliable method for detecting hypo- and hyperventilation. Because metabolism and circulation influence the amount of carbon dioxide eliminated in the lung, capnography monitors these functions too. The plotting of the carbon dioxide concentration as a carbon dioxide-time-diagram draws attention to malfunctions of the equipment. Technical problems of capnography depend on the design of the capnograph (main- or side-stream) used as well as on the weight of the patient. In the discussion the value of pulse oximetry and capnography in detection of critical events during anaesthesia is compared. Capnography is superior to pulse oximetry in the capability to detect critical events. But pulse oximetry complements capnography perfectly, both methods together give a good impression of the patient's state of health. PMID- 7792769 TI - [The clinical situation. Tumor in the sublingual region associated with high grade osteolysis in the masticatory surface of the mandible]. PMID- 7792770 TI - [The hemorrhagic form of acute bovine virus diarrhea: literature review and case report]. AB - Infection of cattle with certain strains of BVD-virus causes a severe thrombocytopenia. The most obvious clinical and pathological lesions are multiple hemorrhages. Until now, problems with the Hemorrhagic syndrome have been reported predominantly from veal calf operations in the U.S.A. This publication presents first a literature review about the Hemorrhagic syndrome. The current data are based upon retrospective studies of field cases and experimental infections. Afterwards clinical, pathological and virological findings from three herds of veal calves in Germany are reported in which hemorrhagic diathesis was observed in calves and BVD-virus was isolated from tissues of diseased calves. The findings in these herds closely resemble the ones described in the literature for the Hemorrhagic syndrome. Therefore, infection with BVD-virus should be considered as differential diagnoses in Germany too, when hemorrhagic diathesis is observed in cattle. PMID- 7792771 TI - [Gynecological laparoscopy in sheep. 1. Foundations]. AB - Laparoscopy is a gentle and safe method for diagnosis and manipulation of the genital tract in female sheep. After a short history outline the equipment and the fundamental principles of the laparoscopy in sheep are described. Possible laparoscopic incidents and their treatment are explained. PMID- 7792772 TI - [Accuracy of current rapid milk progesterone assays in comparison with a routine laboratory method]. AB - Four current commercially available rapid milk progesterone assays (Cowside rapid tube kit [test No. 1], Hormonost-Schnelltest Milch [test No. 2], Hygia Diagnostic RPT Progesterone Test [test No. 3] and Target-Milch-Progesterone-Schnelltest [test No. 4]) for dairy cows were tested for their accuracy in comparison with the gynecological status on the one hand and by using an approved quantitative laboratory-bound assay on the other hand. Milk samples were taken from 23 dairy cows with behavioural oestrus. From 18 species with expected intermediate levels of progesterone milk probes were taken between day 3 and day 6 post insemination and also from 26 gravid cows. The clinically established gynecological status of the dairy cows correlated completely with their milk progesterone values investigated with the laboratory-bound EIA. In contrast the accuracy levels of the rapid progesterone kits differed. The accuracy of test No. 1 was 81% regarding all milk probes, whereas test No. 2 achieved 91%, test No. 3 73.5% and test No. 4 only 69.5%. Milk samples yielding low progesterone levels partly showed big differences. The highest rates of false semiquantitative classifications were recorded in milk samples with intermediate progesterone values. Test No. 2 was the only one with satisfactory results in this range. Milk samples yielding high progesterone values proved to be the best in all four assays. PMID- 7792774 TI - [Publication of a valid determination--cauterization in horses]. AB - Cauterization in horses is a painful method to enable the identification of horses. This method is not allowed (section 17 Nr. 2b Tierschutzgesetz, FRG), because recent findings have found a painless method to identify horses. PMID- 7792773 TI - [Pathological changes in the urogenital tract and mammae of culled sows from an industrial pig production unit]. AB - In an industrial pig production unit 101 sows were culled because of reproduction failure. All the sows had a previous history of MMA, PHS, SUGD. All the sows were crosses of the two breeds Large White and Landrace. 101 sows were examined postmortem for pathologic changes. Changes were found in the kidney (38.6%), pyelum (49.5%), ureter (52.5%), bladder (100%), urethra (100%), uterus (50.5%), cervix (31.7%), vagina (28.7%), ovaries (51.5%), mammary gland (100%). Since 100% of the pathologic findings happened simultaneously in the urinary tract as well as in the mammary gland and just over 50% of the investigated cases had pathologic changes in the genital organs as well, the results suggest that MMA, PHS, and SUGD must be regarded as different manifestations of the same pathological entity of the urogenital organs of the sow. The authors introduce the term SUGD to denominate the conflicting terminology around the periparturient reproductive failure syndrome complex. PMID- 7792775 TI - [Radiologic follow-up examination of podotrochlosis]. AB - X-rays of 205 horses having navicular disease and having been reexamined up to six times are evaluated. For this, the x-rays of each foreleg are evaluated in the dorsopalmar (Oxspring) and lateromedial view. Additionally to changes of the navicular bone, changes of the distal part of the toe are also assessed. Differences can be found in the radiographic process in view of the limitation of vascular foramina and cyst-like lesions. Vascular foramina with sclerotic rim grow less frequent than poorly defined ones and therefore allow for easier prognostication. Cyst-like lesions with sclerotic rim often stay unchanged or decrease separately, whereas poorly defined areas of rarefication show a stronger tendency to expand into the surrounding spongiosa. Changes of vascular and bone structure occur already within a few months, whereas most of the margination changes are already formed in the early stages of disease and proceed slowly. Finally the effects of the therapy are being examined for the radiographic course of disease. Following a neurectomy, a more intensive development of the changes can be observed. The rate of only minimally altered navicular bones as well as the often simultaneous occurrence of changes in the joints of the toe do not allow for a diagnosis only on the basis of radiographic findings. The often slow development of the pathological radiographic changes requires intervals of examination of at least one year and shows that prognostic statements can only be made with caution even after follow-up examinations. PMID- 7792777 TI - [Demonstration of two trimethoprim/sulfonamide combinations in bronchoalveolar lavage fluid of horses and determination of blood levels]. AB - Five healthy horses were given a sulfadoxine/trimethoprim combination (Borgal, Hoechst AG) i.v. on day 1. The next ten days the horses got once a day a sulfadimethoxine/trimethoprim combination orally (Trafigal, Hoechst AG). The doses were given as recommended. One horse received no medicaments for control. On each horse six bronchoalveolar lavages were performed. Blood samples were taken to calculate blood levels and elimination half lives. To determine the amount of substances in lavage fluid and plasma the high performance liquid chromatography (HPLC) was used. Regularly low quantities of sulfonamides and trimethoprim were detected in lavage-samples. The mean plasma concentration (n = 4) of sulfadoxine and trimethoprim 30 min after i.v. administration was 71.6 and 1.13 micrograms/g respectively. 24 h after injection the sulfadoxine blood level was 3.0 micrograms/g, while trimethoprim was no longer detectable. The average elimination half lives of sulfadoxine and trimethoprim were 7.94 h and 1.35 h respectively. 8 h after oral application (n = 5) the highest mean sulfadimethoxine blood levels of 53.8 micrograms/g were measured. The elimination half life of sulfadimethoxine was 9.77 h. Two hours after feeding the drug the first blood samples were taken. They already contained the highest mean trimethoprim concentration of 0.32 microgram/g plasma. PMID- 7792776 TI - [Incidence of Parascaris equorum in foals and their mares after strategic use of wide-spectrum anthelmintics for several years]. AB - In this epidemiological survey 30 foals and their mares from seven breeding farms were investigated. Six farms used wide spectrum anthelmintics strategically at least for three years, on one farm no anthelmintic prophylaxis was practiced. Excretion of P.-equorum-eggs occurred in all breeding farms and in 80% of the foals, but in only one mare. In foals infection with roundworms was detected at the earliest 85 days post partum. Before first shedding of P.-equorum-eggs wide spectrum anthelmintics had been administered to two and to one foal(s) one and two times, respectively, to four animals three times and to one foal each four, five, six and seven times. After metaphylactic use of wide spectrum anthelmintics in the control of an infection with roundworms or other helminths, eggs of P. equorum were found in one foal already 12, 17, 54, 55, 70 and 71 days after treatment with Ivomec-P each and 65 days after use of Panacur in one foal. After application of Banminth roundworm eggs were detected 12, 27, 45, 47, 49 and 62 days in one foal each and 19 and 56 days in two foals each. In eight foals each P.-equorum-eggs were noticed 72 and 196 days after anthelmintic treatment. PMID- 7792778 TI - [Electron microscopic demonstration of viruses in feces of dogs with diarrhea]. AB - 4044 stool samples of dogs with diarrhoea were examined by electron microscopy. The samples were sent for routine diagnostics in the years 1988-1993. Over the examination period virus was detected in 32% of the samples. Parvovirus was diagnosed in 17.2% and coronavirus in 12.4% of the cases. The number of parvovirus-positive samples was lower than in former years, whereas the number of coronavirus-positive samples was higher. Other virus particles (paramyxo-, picorna-, calici- and astrovirus or morphologically similar particles as well as rota- and adenovirus) were altogether detected in 2.5% of the samples. This detection rate corresponded to the results of former years. The majority of parvovirus-positive samples (80.7%) was found in animals aged between six weeks and six months. Of the coronavirus-positive samples 56.5% were detected in dogs older than six months of age and 42.5% in animals between six weeks and six months. In puppies up to six weeks viruses were only detected infrequently (parvovirus 4.7%, coronavirus 0.9%). PMID- 7792779 TI - [Neoplasms originating from large granular lymphocytes in a dog and cats]. AB - Clinical, cytological and pathological findings in three cases of large granular lymphoma in a dog and two cats are presented. These tumors consist of large granular lymphocytes, which have been in part classified as natural killer cells, based on their phenotype and functional aspects. It is likely that such tumors are more frequent than commonly appreciated, because they are only recognized as such in cytological preparations or in electron microscopy. PMID- 7792780 TI - [Morphology of the ligamentum glenohumerale mediale in shoulder joints of dogs]. AB - This study was performed on the shoulder joints of 23 dogs of different age and sex. The purpose was to examine the medial wall of the articulatio humeri as well as the intraarticular position of the ligamentum glenohumerale mediale. The examinations showed an attachment of the ligamentum glenohumerale mediale at the articular capsule by crossing the capsule and forming an intraarticular structure. Section of frozen shoulders showed that the ligamentum glenohumerale mediale separated the cavitas glenoidalis of the scapula and the caput humeri of the humerus from medial like a meniscus. Histological sections were remarkable because of the fibrocartilaginous structure. The attachment of the ligament arised from the tendon of the musculus subscapularis and divided the recessus m. subscapularis into two subpouches. The lateral one was more capacious and more extended under the tendon of m. subscapularis. PMID- 7792781 TI - [Treatment of chronic diarrhea in dogs and cats under field conditions using oral E. coli vaccines]. AB - An autogenous oral E. coli vaccine was tested for efficacy in the treatment of chronic diarrhoea in dogs (n = 82) and cats (n = 50) under field conditions. The data were collected through evaluation of questionnaires completed and returned by veterinarians. After oral application of the E. coli vaccine the symptoms of diarrhoea were stopped in 71% of the treated animals within two to five days. In further 15% of the cases the enteric symptoms continued but were not so severe as in the beginning of the treatment. There was no therapeutic success with the oral E. coli vaccine in further 14% of the animals in cause of food allergy, ascariasis, volvulus or pancreatic insufficiency. PMID- 7792782 TI - [Domestic animals as patients in a small animal practice. 2. Handling, sex determination, blood collection, drug application]. AB - The importance of small pets as domestic animals and patients in veterinary practice increased in the last years. Differences in physiology and behaviour require exact knowledge of appropriate handling and sex determination, techniques of blood collection as well as drug application methods. Therefore, a survey of rabbit, guinea-pig, chinchilla, hamster, gerbil, mouse, and rat as patients in veterinary practice is given. PMID- 7792783 TI - [Clinical symptoms and diagnosis of feline infectious peritonitis]. AB - Body effusions from 197 cats and blood serum samples from 252 cats, where Feline Infectious Peritonitis (FIP) was part of the differential diagnosis, were analysed. The diagnoses were confirmed by clinical follow up or histopathology. The final diagnosis FIP was always confirmed by histopathology. The median age of cats with FIP was 1.6 years. FIP was responsible for 41% of the body effusions, whereas malignomas caused 24%, cardial insufficiencies 14% and purulent serositis 12% of the body effusions. The rivalta test was highly sensitive for FIP. Predictive value of a negative result was 100%, predictive value of a positive result was 84%. In half of the cases with purulent serositis and in 20% of malignomas rivalta reacted positive. The cardial insufficiencies were negative for rivalta. Coronavirus antigen could be demonstrated by immunofluorescence in 34 of 49 body effusions caused by FIP, whereas in the 50 body effusions caused by other diseases no coronavirus antigen was detected. An albumin globulin ratio of < 0.6 was highly diagnostic for an inflammatory process, nearly exclusively for FIP. An albumin globulin ratio of > or = 0.8 almost excluded FIP. Only a negative or very high (1:1600) FIP titer could contribute to confirm diagnosis. Low and medium titers, however, should not be interpreted. PMID- 7792784 TI - Bronchial hyperreactivity in the peripheral airways. PMID- 7792785 TI - Eosinophils infiltration in the rat seminal vesicle associated with estradiol-17 beta-related stromal proliferation. AB - We performed a histological quantitative analysis of collagen and smooth muscle in seminal vesicle (SV) stroma after Estradiol-17 beta (E2) administration to the immature castrated rat. On day 14 after E2 administration, collagen and smooth muscle had increased approximately five and fifteen times, respectively, over the baseline of day 0. On day 28 (14 days after the cessation of E2 administration), smooth muscle decreased to the same level as that on day 7, but collagen did not decrease during the 14 days after the cessation of E2 administration. As the proliferation of stroma, the infiltration of eosinophils was seen in the perigrandular stroma that consisted of rich collagen. The number of infiltrated eosinophils increased exponentially in the period in which collagen proliferated. But in the peripheral stroma which consists of rich smooth muscle, no eosinophil infiltration was seen. These results suggest that eosinophil infiltration into SV is related to E2 administration and to stromal proliferation, especially to collagen proliferation in this condition. PMID- 7792786 TI - Evaluation of the effectiveness of cervical cancer screening: a case-control study in Miyagi, Japan. AB - To estimate the effectiveness of screening for invasive cervical cancer, a case control study was performed in Miyagi, Japan. A total of 198 cases (129 mass screen-detected and 69 outpatient-detected) of invasive cervical cancer were identified between 1984 and 1990. The results of the Papanicolaou smear of these cases were compared to those of 396 age- (+/- 5 years) and area-matched controls. Compared with women who had no prior screening (cases 51.6%, controls 16.2%), women who were screened had an odds ratio (OR) for invasive cervical cancer of 0.14 (95% confidence interval [CI] 0.088-0.230). The OR for the 175 cases of squamous cell carcinoma was 0.13 (95% CI 0.077-0.215), while the OR for the 23 cases of screened women with adenocarcinoma was 0.40 (95% CI 0.091-1.753). The time intervals following the last negative smear were assessed and we found an OR for a one-year interval and a two-year interval of 0.09 (95% CI 0.055-0.163) and 0.17 (95% CI 0.083-0.335), respectively. In conclusion, screening for invasive cervical cancer is not only effective but also the degree of protection is high for one to two years. PMID- 7792787 TI - Viability of partial liver graft from living donor in pigs. AB - For evaluation of the viability of partial liver graft from a living donor, we investigated energy production of mitochondria and radical scavenging enzyme activities in partial and whole liver transplantation in pigs. The values of adenosine triphosphate (ATP) and total adenine nucleotide (TAN) of the partial liver graft were higher than those of the whole liver graft, whereas the hypoxanthine of the partial liver graft was lower than that of the whole liver graft. There was no statistical difference in the radical scavenging enzyme activities between the two groups. The values of respiratory control ratio (RCR) in both groups were above 3.0 and there was no statistical difference. The survival rates of pigs received partial liver and whole liver graft with 2 to 3 hr cold preservation was 71% and 91%, respectively and there was no statistical difference between two groups. These results suggest that viabilities of the partial liver graft from the living donor are satisfactory enough, compared with those of whole liver graft from a cadaver. PMID- 7792788 TI - Longitudinal investigation of epidemiologic feature of adenovirus infections in acute respiratory illnesses among children in Yamagata, Japan (1986-1991). AB - Using human embryonic fibroblast (HEF) and HEp-2 cell cultures, adenoviruses were isolated from 989 (3.7%) out of 26,793 pediatric patients with ARI in Yamagata, Japan from January, 1986 to December, 1991. All isolates were identified as types 1 (Ad1)-6 and no other serotypes were identified. Epidemiologic feature was different depending on the subgenus group. Ad1, 2, 5 and 6 (group C) were endemic and the infections occurred frequently in the summer season. Ad3 (group B) was epidemic in the autumn to winter season, although the virus was isolated every month in non-epidemic season. No seasonal distribution of Ad4 (group E) could be determined because the number of patients was limited. Neutralizing antibody positive ratio for group C were more than 40% at 1-2 years of age and almost 100% by 10 years of age but those for Ad3 (group B) were 40% by 10 years of age. The neutralizing antibodies for Ad4 (group E) or Ad7 (group B) became negative by 10 years of age. With group C infections, most cases were infants and young children less than 2 years of age, but Ad3 infections were older children with the peak at 4 and 5 years of age. PMID- 7792789 TI - Vascularization and innervation of the canine wrist joint synovial membrane. AB - The correlation between vascular distribution and synovial structures was investigated using corrosion cast of the synovial fold of the dog antebrachiocarpal joint (wrist joint) under scanning electron microscopy. Arterial branches arose from a main artery deep in the subsynovial layer, ascended toward the free margin of the fold, dividing into several branches, and finally formed a dense capillary network beneath the lining layer. Immunohistochemical study and a retrograde axonal tracing experiment revealed that almost all nerve fibers were associated with the arterial tree and that: (1) proximal parts of the arterial tree were innervated with neuropeptide Y (NPY) containing noradrenergic sympathetic fibers, vasoactive intestinal peptide containing non-catecholaminergic sympathetic fibers from the stellate ganglion and substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing sensory fibers from the C7-T1 segments of the dorsal root ganglia; (2) more distal parts of the arterial branches were associated with NPY-immunoreactive sympathetic fibers and SP- and CGRP-immunoreactive sensory fibers; and (3) the most peripheral precapillary arterioles were accompanied by only SP- and CGRP containing sensory fibers. These results indicate that synovial blood flow is regulated by at least three different nerve systems which possess regional differences. PMID- 7792790 TI - Ganglioglioma in the basal ganglia totally resected by a trans-distal Sylvian approach. AB - A patient with a ganglioglioma in the basal ganglia is presented. An 18-year-old man presented with involuntary movement in his right hand and right homonymous hemianopsia. Computed tomography and magnetic resonance imaging revealed a cystic tumor with an enhancing nodule in the basal ganglia extending into the thalamus. The mass was totally resected by a trans-distal Sylvian approach and was histologically proven to be a ganglioglioma. This is a rare case of midline ganglioglioma in a patient who underwent gross total resection. PMID- 7792792 TI - A cell-specific nuclear receptor regulates the steroid hydroxylases. AB - Recent studies of the gene regulation of the cytochrome P450 steroid hydroxylases have established a key role for an orphan nuclear receptor, designated steroidogenic factor 1 (SF-1). SF-1 binds to shared promoter elements upstream of the steroid hydroxylases to mediate their coordinate expression in steroidogenic cells. Analyses of SF-1 expression during mouse embryonic development showed that SF-1 is expressed from the earliest stages of organogenesis of the steroidogenic tissues, suggesting an intimate link between SF-1 and steroidogenic cell differentiation. Finally, in gene disruption experiments, the gene encoding SF-1 was shown to be essential for development of the adrenal glands and gonads. These results establish the essential role of this orphan nuclear receptor in the development and function of the primary steroidogenic tissues. PMID- 7792791 TI - Aldosterone and Hypertension. Proceedings of a satellite symposium to the 15th International Society of Hypertension Congress. Lorne, Victoria, Australia, March 17-19, 1994. PMID- 7792793 TI - Recognition of markers of response to potassium-canrenoate in essential hypertension. AB - Potassium canrenoate (K-Can) prevents hypertension in Milan hypertensive strain (MHS) but not in spontaneously hypertensive rats (SHR). Essential hypertensive patients (HT) may have differential sensitivity to diuretics, since a subgroup of HT insensitive to hydrochlorothiazide (HCTZ) but sensitive to K-Can has previously been found. The aims of this study were: 1) to seek markers of response in essential hypertensive patients selectively sensitive to K-Can: and 2) to test whether selective sensitivity to furosemide may also be demonstrated. After 2 weeks of placebo (P) 50 uncomplicated, mild to moderate HT (46 +/- 9 yrs, mean +/- SD) received K-Can (50 mg/day) for 4 weeks. After 2 more weeks of P, patients received HCTZ (25 mg) and furosemide (25 mg) for 4 weeks each in a single blind crossover design, with 2 weeks P between each treatment. Dosages were doubled after 2 weeks if diastolic blood pressure (DBP) was > 90 mmHg. Responders (R) were those HT whose DBP was < or = 90 mmHg and/or at least 10 mmHg lower than before treatment. Systolic blood pressure (SBP)/DBP was measured every 2 weeks with plasma renin activity (PRA), red blood cell Na(+)-K(+)-Cl- cotransport (COT) and Na(+)-K+ ATPase pump activity measured at the end of the first P period, and serum electrolytes at the end of each period. Four HT dropped out because of low compliance, 6 because of reversible side effects, and 1 because blood pressure was not back to pre-treatment value after the second placebo period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792795 TI - Aldosterone (ALDO) increases transmembrane influx of Na+ in vascular smooth muscle (VSM) cells through increased synthesis of Na+ channels. AB - We have previously reported our studies on glucocorticoid (GC) effects on Na+ influx in vascular smooth muscle (VSM) cells. We now report a parallel study on the effect of mineralocorticoid (MC) on Na+ influx in VSM cells. Unidirectional influx of Na+ was measured in cultured cells of rabbit aortic media with 22Na as tracer. Cells were treated with near physiologic (5 nM) or supraphysiologic (50 nM) aldosterone (ALDO) for 24 or 48 hours, or for 7 to 10 days, in the presence of competitive inhibitors of MC-receptor binding, K-prorenoate (PRN), or GC receptor binding, RU 486. ALDO at 5 nM increased Na+ influx by 98% +/- 12%, but only after 7-10 days of treatment. This effect was inhibited by PRN, but not by RU 486, and blocked by amiloride but not by ethylisopropyl-amiloride or by dichlorobenzamil (DCB). In VSM cell membranes from aortae of rabbits treated in vivo with ALDO (2 mg/day) for 4 weeks. Na+ channels were quantified by determination of specific [3H]amiloride binding in the presence of excess of DCB and EIPA to exclude tracer binding from the Na+/Ca2+ exchanger and the Na+/H+ antiporter. ALDO doubled the number of of Na+ channels in such isolated cell membranes, as determined by Bmax per mg membrane protein. We propose that this vascular effect of ALDO may constitute an important pathogenetic mechanism of hypertension induced by chronic excess of MC, in addition to the well known renal mechanism. PMID- 7792794 TI - Ouabain-inhibiting activity of aldosterone antagonists. AB - It has been suggested that endogenous substances (known as ouabain-like factors, OLF), secreted from the central nervous system in response to salt and water retention, inhibit the cell membrane Na+/K+ pump in the renal tubules and reduce sodium reabsorption. However, by also acting upon vascular smooth muscle cells, they may induce cell Na+ and Ca++ accumulation, vasoconstriction and systemic hypertension. Recently, an endogenous Na+/K+ pump inhibitor was isolated from human plasma; this inhibitor is indistinguishable from the cardiac glycoside ouabain based on biochemical and immunological criteria. Its plasma concentration is close to the therapeutic range for ouabain (around 0.4 nmol/L). Since plant ouabain promotes natriuresis, vasoconstriction, and hypertension; endogenous ouabain may therefore control extracellular fluid volume and blood pressure. The highest plasma concentrations of endogenous ouabain and OLF were found in congestive heart failure, aldosterone producing adenoma, human and animal models of volume expanded hypertension (reduced renal mass and DOCA-salt hypertension), and in Milan hypertensive rats (MHS). Aldosterone antagonists (canrenone and canrenoate) exert both agonist and antagonist effects on the digitalis receptor site of the Na+/K+ pump. They are effective antihypertensive agents in animal models of hypertension sustained by OLF (reduced renal mass-Na+ and DOCA-salt hypertension in rats). Moreover, in a subgroup of essential hypertensives, 4 weeks of canrenoate administration reduced blood pressure, heightened red blood cell Na+/K+ pump activity, and antagonized ouabain-induced vasoconstriction. None of these effects was seen in the other hypertensives. These data suggest that aldosterone antagonists stimulate the Na+/K+ pump inhibited by endogenous ouabain and exert their antihypertensive action at least in part through this mechanism. PMID- 7792796 TI - Aldosterone biosynthesis and action in vascular cells. AB - In view of the hypothetical possibility that the vascular renin-angiotensin system (RAS) might include aldosterone biosynthesis and action in the vasculature, we have undertaken a study to identify aldosterone released into the perfusion circuit from the rat mesenteric artery, and to investigate the effects of an angiotensin converting enzyme inhibition (ACEI) on aldosterone production from the vasculature. After 30 min equilibration, 240 mL of perfusate was collected and subjected to reverse-phase HPLC and subsequent mass spectrometry. Mass spectra corresponding to authentic corticosterone and aldosterone were obtained from the samples of mesenteric artery perfusate. Production of aldosterone in the mesenteric artery was not changed by adrenalectomy, although it was reduced in the arterial perfusate from rats pretreated with ACEI. By RT PCR the expression of CYP 11B2 and mineralocorticoid receptor genes were demonstrated in both vascular endothelial and smooth muscle cells. These studies constitute indirect evidence supporting our hypothesis that locally produced aldosterone in the vascular tissue acts on vascular tone and remodeling via a paracrine or autocrine manner. PMID- 7792798 TI - Adrenal steroids and cardiac fibrosis. AB - Uninephrectomized rats maintained on 0.9% NaCl as drinking fluid and infused for 8 weeks with aldosterone 0.75 micrograms/h via subcutaneous osmotic minipumps respond with hypertension, cardiac hypertrophy, and both interstitial and perivascular cardiac fibrosis. Similar animals injected with desoxycorticosterone (20 mg/week), or the glucocorticoid antagonist RU 486 (2 mg/day) show interstitial cardiac fibrosis to a lesser degree than animals injected with aldosterone, and show perivascular fibrosis to a greater degree. These findings suggest that glucocorticoid antagonist activity may play a role in exacerbating perivascular collagen deposition in response to chronic mineralocorticoid and salt imbalance. PMID- 7792797 TI - Chronic mineralocorticoid excess and cardiovascular remodeling. AB - Chronic mineralocorticoid (MC) excess, whether due to elevated plasma aldosterone (ALDO) or deoxycorticosterone (DOC), is associated with a perivascular fibrosis of systemic and coronary arterioles. This remodeling of resistance vessels contributes to the appearance of hypertension. Chronic MC excess is also accompanied by cardiac myocyte necrosis, secondary to myocardial potassium depletion, and a subsequent reparative fibrosis that appears in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles. Fibrosis contributes to the appearance of ventricular arrhythmias and dysfunction. Herein, clinical and experimental evidence linking chronic, inappropriate (relative to dietary sodium) elevations in circulating ALDO and DOC with these reactive and reparative forms of fibrous tissue formation in the heart and other tissues is presented. PMID- 7792799 TI - Significance of 19-noraldosterone, a new mineralocorticoid, in clinical and experimental hypertension. AB - 19-Noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, possesses potent mineralocorticoid and hypertensinogenic activities. 18,19-Dihydroxycorticosterone (18,19-(OH)2-B) and 18-hydroxy-19 norcorticosterone (18-OH-19-nor-B), a possible precursor of 19-noraldosterone, have been identified in human urine. These mineralocorticoid hormones are regulated by the renin-angiotensin system and synthesized in adrenal glomerulosa cells. Urinary 19-noraldosterone correlated with urinary 18,19-(OH)2-B, 18-OH-19 nor-B, 18-hydroxycorticosterone (18-OH-B), and aldosterone. Urinary excretion of 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B were increased in patients with aldosterone-producing adenoma (APA) and in those with idiopathic hyperaldosteronism (IHA), but the two did not differ significantly. Urinary 18-OH B and 18-hydroxycortisol (18-OH-F) were significantly higher in APA compared with IHA. Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, urinary 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B could not be used to distinguish the two subsets of primary aldosteronism. Urinary 19-noraldosterone did not differ in hypertensive and normotensive patients. However, urinary 19 noraldosterone was increased in some hypertensive patients. In spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), urinary 19-noraldosterone was increased at the prehypertensive stage compared with Wistar-Kyoto (WKY) rats. Urinary 19-noraldosterone was decreased in 9-week-old SHR and SHRSP compared with WKY rats. However urinary 19-noraldosterone was higher in SHRSP than in SHR. These elevated levels of 19-noraldosterone may contribute to hypertension in some individuals and in experimental hypertensive rats. PMID- 7792800 TI - Cortisol to cortisone: glucocorticoid to mineralocorticoid. AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), by converting cortisol and corticosterone to hormonally inactive cortisone and 11-dehydrocorticosterone, respectively, is an important pre-receptor signaling pathway for the renal mineralocorticoid receptor (MR). This receptor has an equal affinity for the glucocorticoids, cortisol and corticosterone, and for the mineralocorticoid, aldosterone. In states of 11 beta-HSD deficiency such as the syndrome of apparent mineralocorticoid excess (AME) and licorice ingestion, cortisol acts as a potent mineralocorticoid. In addition to the established and cloned type I 11 beta-HSD, a second 11 beta-HSD isoform has been reported in rabbit kidney and human placenta. We have analyzed the kinetics of 11 beta-HSD activity in human kidney and compared it with the expressed human type I 11 beta-HSD cDNA. Microsomes were prepared from mid-gestational human fetal kidneys and incubated with various concentrations of cortisol (0.0125-10 microM) and NAD or NADP. Kinetic analysis revealed a high affinity (apparent Km 60 nM) isoform, the activity of which was exclusively NAD-dependent. No convincing NADP-dependent activity was seen. Similarly with cortisone as a substrate no 11-oxoreductase activity was evident. In contrast, when type I human 11 beta-HSD was ligated into the expression vector pcDNAI and transiently transfected into COS-I cells, low affinity (apparent Km 2.1 microM) NADP-dependent activity was seen. 11-Oxoreductase activity was also observed. The cloned type I human 11 beta-HSD encodes an enzyme with both low affinity, NADP-dependent, dehydrogenase and 11-oxoreductase activities, but this activity is absent in human fetal kidney (and probably adult kidney).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792801 TI - Evidence for the regulation of Na+, K(+)-ATPase alpha 1 gene expression through the interaction of aldosterone and cAMP-inducible transcriptional factors. AB - Mineralocorticoid hormones such as aldosterone modulate cellular ion homeostasis at least in part through the regulation of Na+, K(+)-ATPase (NAKA) gene expression. While aldosterone acts at the transcriptional level through its ligand-inducible mineralocorticoid receptor (MR), tissue specific and other transcriptional factors may interact with the MR to modulate this regulatory response. cAMP also regulates NAKA alpha 1 gene expression which at the transcriptional level is mediated, in part, through a cAMP response element (CRE) present on a highly conserved, 48 base pair enhancer region, the PUC-1 core, of the rat NAKA alpha 1 subunit gene promoter. We have tested the hypothesis that the MR interacts with cAMP induced transcriptional factors to modulate the NAKA alpha 1 gene expression. In transient transfection studies a PUC-1 core attached to an enhancerless SV40 promoter driven reporter gene (pB1CAT) was induced by 8 bromo-cAMP in HeLa cells. Co-transfected MR expression vector inhibited the 8 bromo-cAMP inducible activity of pB1CAT. DNA binding studies suggested that the PUC-1 core binds both CREB/ATF proteins as well as the glucocorticoid hormone class of steroid receptors. These results suggest that the MR suppresses cAMP mediated activation of PUC-1 core driven CAT activity possibly through a direct interaction with CREB/ATF transcriptional factors. This in turn suggests that the interaction of two distinct signal transduction systems, aldosterone and cAMP, may define the mineralocorticoid responsiveness of the Na+, K(+)-ATPase alpha 1 gene. PMID- 7792802 TI - Inborn errors of aldosterone biosynthesis in humans. AB - Corticosterone methyl oxidase (CMO) type I and type II deficiencies are inborn errors at the penultimate and ultimate steps in the biosynthesis of aldosterone in humans. Recently, steroid 18-hydroxylase (P450C18), or aldosterone synthase (P450aldo), was shown to be a multifunctional enzyme catalyzing these two steps of aldosterone biosynthesis, i.e., the conversion of corticosterone to 18 hydroxycorticosterone and the subsequent conversion of 18-hydroxycorticosterone to aldosterone. This observation suggests that CMO I and CMO II deficiencies are derived from two different mutations in the P450C18 gene (CYP11B2). To elucidate whether or not this is the case, we performed molecular genetic studies on CYP11B2 of both types of patients. Nucleotide sequence analysis has indicated that the gene of CMO I deficient patients is completely inactivated by a frameshift to form a stop codon due to a 5-bp nucleotide deletion in exon 1. Sequence analysis of CYP11B2 of CMO II deficient patients has revealed two point mutations, CGG-->TGG (Arg181-->Trp) in exon 3 and GTG-->GCG (Val386-->Ala) in exon 7. CYP11B1, the gene for steroid 11 beta-hydroxylase (P45011 beta) which was previously postulated to be the target for CMO II deficiency, is not impaired in these two types of patients. Expression studies using the corresponding mutant cDNAs have shown that CMO I deficient patients are null mutants with a complete lack of P450C18 whereas CMO II deficient patients are leaky mutants with an altered P450C18 activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792803 TI - Nongenomic aldosterone effects: the cell membrane as a specific target of mineralocorticoid action. AB - Studies in extrarenal, nonepithelial cells such as human lymphocytes and smooth muscle cells indicate that aldosterone produces not only delayed genomic effects, but also rapid, non-genomic effects on transmembrane electrolyte movements. These non-genomic events involve the immediate activation of the sodium/proton exchanger of the cell membrane at very low, physiological concentrations of aldosterone in both lymphocytes and cultured rat vascular smooth muscle cells. This new pathway for mineralocorticoid action is further characterized by a 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response. Aldosterone-specific binding sites have been demonstrated in the plasma membrane of human lymphocytes, with features identical to those seen for the rapid aldosterone effects in the same cells. As second messenger the inositol 1,4,5-trisphosphate pathway has been identified both in human lymphocytes and vascular smooth muscle cells, which respond over the same rapid time course. In addition, the aldosterone effect on inositol-1,4,5-trisphosphate production in vascular smooth muscle cells is sensitive to pertussis toxin, but not to cholera toxin, pointing to a possible involvement of G-proteins in the cellular signalling. This article reviews the data supporting a new, two-step model for successive non-genomic and genomic mineralocorticoid effects. PMID- 7792804 TI - Familial pseudohypoaldosteronism: a review on the heterogeneity of the syndrome. AB - Pseudohypoaldosteronism is thought to be a rare salt-losing disorder, caused by resistance to the action of aldosterone. Defective aldosterone receptor binding is present in familial as well as sporadic cases and it has been suggested that the pathogenesis is due to a defect in the aldosterone receptor system. To date, however, molecular genetic analysis has been unable to identify a mutation in the aldosterone receptor gene itself. We have reviewed the findings in patients with pseudohypoaldosteronism, for clues which might enable us to identify the underlying pathogenesis. Although aldosterone receptor binding is regularly decreased or absent in monocytes of patients with pseudohypoaldosteronism, in some patients receptor protein can be detected with a fluorescence-labeled antibody. Receptor protein was detected in patients from familial autosomal dominant families and in sporadic cases, but was undetectable in two patients with the familial recessive form. To further elucidate the pattern of inheritance we studied the response of the renin-angiotensin-aldosterone system to the stimulation by sodium depletion in the familial autosomal dominant form and in two families with sporadic cases. In both "sporadic" families investigated, one parent and one sibling had an exaggerated response of renin and aldosterone to sodium depletion indicating a defect of sodium conservation apparent only during stress, leading to reclassification as familial cases. No additional family member in the "classical" autosomal dominant families responded abnormally to sodium depletion. These findings indicate that pseudohypoaldosteronism is unusually heterogeneous in its clinical, biochemical, and genetic presentations and findings and suggest that its pathogenesis is heterogeneous as well. PMID- 7792805 TI - Pseudohypoaldosteronism: evaluation of type I receptors by radioreceptor assay and by antireceptor antibodies. AB - We have previously demonstrated a deficiency of mineralocorticoid receptors in pseudohypoaldosteronism, by radioreceptorassay. We now report findings with an antireceptor antibody derived from the immunogenic region of the receptor. Lymphocytes from normal controls and from two cases of pseudohypoaldosteronism previously shown to lack receptor binding were tested. After the plasma membrane of lymphocytes was permeabilized with methanol the cells were incubated with a 1:200 dilution of antibody followed by fluorescent antirabbit immunoglobulin mouse serum. After washing fluorescence was detected by microscopy and cytofluorimetry in both controls and patients with pseudohypoaldosteronism. Recent studies on mineralocorticoid receptor cDNA in pseudohypoaldosteronism have not established a mutation in the sequence. We thus suggest that the pathogenesis of pseudohypoaldosteronism is not related to an abnormality of the receptor but rather due to intracellular factor(s) which can block the binding of aldosterone to its receptor. PMID- 7792806 TI - Molecular characterization of the mineralocorticoid receptor in pseudohypoaldosteronism. AB - Pseudohypoaldosteronism (PHA) is characterized by salt-wasting and failure to thrive in the newborn, accompanied by high urinary levels of sodium despite hyponatremia, hyperkalemia and metabolic acidosis, elevation of plasma renin activity, and high plasma aldosterone levels. PHA patients are resistant to mineralocorticoid administration, but their symptoms ameliorate after a period of sodium supplementation, which can be discontinued in older subjects. Binding studies performed on mononuclear leukocytes of the family members affected by the disease have shown the absence of binding of [3H]aldosterone to the mineralocorticoid receptor (MR) in mononuclear leukocytes in two siblings and a marked reduction in another sibling and the father, suggesting either the absence of MR or a defect in the ligand binding domain of the MR in these patients. Molecular analysis of the MR in the members of this family did not reveal any major rearrangement or deletion of the MR gene. In addition, no mutation was found in the entire MR coding sequence by RT-PCR and direct sequencing of MR mRNA, and the semiquantitative RT-PCR analysis of the MR mRNA of one affected patient failed to show any quantitative abnormality in MR expression. These results do not exclude a molecular abnormality present in the MR gene being responsible for PHA. However, they indicate that in this family PHA is not related to a modification of the MR primary structure or to a major abnormality in MR expression. PMID- 7792807 TI - Pseudohypoaldosteronism: options for consideration. AB - Pseudohypoaldosteronism (PHA), or mineralocorticoid resistance, displays several features which distinguish it from other steroid resistance syndromes: while at presentation the clinical manifestations may be severe, patients almost invariably survive into adulthood without ill effects in the absence of ongoing treatment; patterns of inheritance are very variable; and, in addition to the more common primary form, it may develop secondary to a variety of conditions. Although the clinical presentation and the finding of absent or greatly diminished binding of aldosterone by peripheral blood leukocytes strongly suggest an underlying abnormality involving the mineralocorticoid receptor (MR), no abnormality in the MR has been identified, unlike other forms of resistance to hormones in the steroid superfamily, in which the underlying abnormality has been traced to a defect in the gene encoding the receptor protein. Molecular studies of the index case have excluded a major cytogenetic abnormality and major deletions or rearrangements of the MR gene. They have also shown that the cDNA sequence corresponding to the open reading frame of the mineralocorticoid receptor molecule is normal, compared with the published human MR cDNA sequence, and that MR mRNA is expressed in apparently normal quantities in peripheral blood mononuclear leukocytes. These findings raise a number of questions about the underlying mechanism for PHA and the mechanisms by which homeostasis is achieved in the absence of effective aldosterone action. With respect to the mechanism(s) of PHA, several possibilities can be envisaged. It is possible, albeit unlikely, that by unfortunate chance small mutations have been missed as a result of cloning only normal alleles in heterozygous patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792808 TI - Syndromes of glucocorticoid and mineralocorticoid resistance. AB - Glucocorticoid resistance results from incomplete but apparently generalized inability of glucocorticoids to exert their effects on their target tissues. The condition is associated with compensatory elevation of circulating ACTH and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from asymptomatic to different degrees of hypertension and/or hypokalemic alkalosis and/or hyperandrogenism, caused by elevation cortisol and other salt-retaining steroids, and of adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, male type baldness, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility; and in children to precocious puberty. Different molecular defects, such as point mutations or microdeletions of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by different degrees of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids and/or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor. Mineralocorticoid resistance results from the inability of aldosterone to exert its effect on target tissues. The syndrome is associated with salt loss, hypotension, and hyperkalemic acidosis. We have cloned and sequenced the cDNA of five unrelated patients with this syndrome and have not found any mutations of pathophysiological significance that would explain the resistance of these patients to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792809 TI - Evidence for a novel mechanism of androgen resistance in the human prostate cancer cell line, PC-3. AB - Progression to hormone-refractory disease is a common outcome of human prostate cancer. In this study, we have investigated the basis of androgen insensitivity in the human prostate cancer cell line, PC-3, which was derived from a bone metastasis of a hormone-refractory prostate cancer. PC-3 cells with virtually undetectable (PC-3AR-) or low (PC-3AR+) levels of androgen receptor (AR) RNA expression were examined. RNase protection assays demonstrated that the level of AR RNA in PC-3AR+ cells was similar to that in a normal androgen-responsive genital skin fibroblast cell strain. Quantitative immunocytochemical staining of AR in PC-3AR+ cells using antibodies directed against the amino and carboxyl termini of the receptor revealed staining in 30% of cells with either antibody. Furthermore, the level of AR staining in PC-3AR+ cells was higher than in the androgen-responsive breast cancer cell lines ZR-75-1, T47-D, and MCF-7. Despite the expression of AR RNA and protein, PC-3AR+ cell proliferation was unaffected by the presence of 0.1-10 nM mibolerone. Scatchard analysis demonstrated a complete absence of specific [3H]dihydrotestosterone ([3H]DHT) binding to PC-3AR+ cytosolic extracts, which could not be explained by structural alterations in the AR gene. The sizes of individual AR exons amplified from genomic DNA derived from PC-3AR+ cells were identical to those amplified from normal human cells. Furthermore, sequence analysis did not reveal a mutation in the DNA- or hormone binding domains of the AR gene in PC-3AR+ cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792810 TI - Aldosterone: the minority hormone of the adrenal cortex. AB - In comparison with the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone is a minority hormone of the mammalian adrenal cortex, and its proper function is dependent upon protective physiological mechanisms. These include a particular site of aldosterone synthesis in zona glomerulosa cells as well as a complex multifactorial control system, which adapts aldosterone production to acute and chronic changes in body sodium and potassium contents, irrespective of pituitary ACTH secretion. In the course of the last few years, an important element of these mechanisms has been identified in the form of the enzyme involved in the final steps of aldosterone biosynthesis. In species such as the human, rat, and mouse, the conversion of deoxycorticosterone to aldosterone is catalyzed by an isozyme (CYP11B2) of cytochrome P450(11 beta) (CYB11B1). The gene encoding this enzyme is expressed only in the zona glomerulosa. Its transcription is enhanced by sodium deficiency and potassium intake, but is suppressed by long-term administration of high doses of ACTH. In contrast, the gene encoding CYP11B1, i.e., the major (non-aldosterone producing) type of the enzyme, is expressed mainly in the zona fasciculata, and its expression depends on physiological concentrations of ACTH. In other animal species (cattle, pig), the major forms of cytochrome P450(11) beta have an inherent aldosterone-synthesizing activity, which is, however, selectively suppressed in mitochondria of zona fasciculata cells by yet unknown mechanisms. PMID- 7792811 TI - Genetic recombination as a cause of inherited disorders of aldosterone and cortisol biosynthesis and a contributor to genetic variation in blood pressure. AB - CYP11B1 (11 beta-hydroxylase) and CYP11B2 (aldosterone synthase) are steroidogenic enzymes which mediate the final step (11 beta-hydroxylation) in cortisol synthesis and the final three steps (11 beta-hydroxylation, 18 hydroxylation, and 18-oxidation) in aldosterone synthesis, respectively. The enzymes share 93% identity in amino acid sequence and are encoded by two structurally similar genes which are located in tandem on chromosome 8q22, approximately 40 kb apart. Expression of the aldosterone synthase gene (CYP11B2) is limited to the zona glomerulosa of the adrenal cortex, thereby limiting the synthesis of aldosterone to that zone, where it is principally regulated by plasma levels of angiotensin II and potassium. The 11 beta-hydroxylase gene (CYP11B1) is expressed in the zona fasciculata, the zone which also expresses a 17-hydroxylase activity, where it mediates cortisol synthesis under the control of ACTH. Genetic recombination involving a mispairing of the two CYP11B genes can lead to duplications and deletions of the genes, creation of hybrid genes of several forms, or transfer of coding and regulatory sequences from one gene to the other. Since the two genes have related but different activities, are normally expressed in different zones, and respond to different physiological signals, such recombination has the potential to generate a variety of inherited disorders of steroid production. In this paper we review the range of mutations which can occur and the resulting disorders of steroid biosynthesis, and suggest some novel mutations which might be sought in variants of these endocrinological syndromes. PMID- 7792812 TI - Type 1 angiotensin II receptors of adrenal tumors. AB - The present study was designed to clarify the transcriptional regulation of the human type 1 angiotensin II receptor (AT1) gene and its pathophysiological roles in steroidogenesis by adrenal tumors. A cDNA encoding type 1 angiotensin II receptor (AT1) was isolated from a human liver cDNA library encoding a protein of 359 amino acids with seven transmembrane segments. It is very likely that human has only one type of AT1 receptor, in contrast with rodents. A genomic clone containing 217 bp of exon 1 and 2558 bp of the 5'-flanking region of human AT1 receptor gene was isolated. Its proximal promoter region contained putative TATA and GC boxes, CRE and AP1 sites. Aldosterone-producing adenoma (APA) contained significantly higher levels of mRNA for AT1 and ACTH receptors than normal tissues adjacent to APA. There were no mutations within the cytoplasmic third loops of AT1 and ACTH receptors in APAs examined. APA showed increased expression of the mRNA for P450c11 and decreased expression of the mRNA for P450c17. These results suggest that renin-independent overproduction and clinically observed ACTH-dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes. The mechanism of the discordantly increased expression of AT1 receptor in APA remains to be clarified. PMID- 7792813 TI - Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes. AB - Primary aldosteronism is the commonest cause of potentially curable hypertension when diagnosed in both florid and less florid forms. Genetic screening, so far available only for glucocorticoid-suppressible hyperaldosteronism, permits diagnosis from birth, before any biochemical or clinical abnormalities appear. Biochemical screening using the aldosterone-to-renin ratio permits diagnosis in the absence of raised aldosterone or of hypokalemia. Primary aldosteronism occurs in several familial forms. As well as the variety described in 1966 which is ACTH dependent and glucocorticoid-suppressible, and not so far associated with tumors, another variety described in 1991 is not glucocorticoid-suppressible and is frequently associated with aldosterone-producing adenomas (APAs). Primary aldosteronism due to adrenocortical hyperplasia, adenoma, or carcinoma can also occur as part of the multiple endocrine neoplasia syndromes, where normoplasia, hyperplasia, benign neoplasia, and malignant neoplasia can exist in the same patient in the same endocrine gland(s) at the same time. The morphology of adrenocortical hyperplasia causing primary aldosteronism ranges from glomerulosa like (idiopathic hyperplasia of the adrenals) to fasciculata-like (glucocorticoid suppressible hyperaldosteronism). The morphology of adrenocortical neoplasia causing primary aldosteronism can also be either predominantly glomerulosa-like or fasciculata-like, in our experience equally often. Varying morphology of APAs is associated with varying responses of aldosterone to angiotensin II. Tumors predominantly fasciculata-like are unresponsive to angiotensin II, whereas those predominantly glomerulosa-like are responsive to angiotensin II. Both subtypes can be seen in a single family. Primary aldosteronism represents a spectrum of genetic disorders resulting in hyperplasia or neoplasia, but all are associated with some degree of autonomy of aldosterone production, independent of the renin angiotensin system. PMID- 7792814 TI - Significance of steroidogenic enzymes in the pathogenesis of hyperfunctioning and non-hyperfunctioning adrenal tumor. AB - To elucidate the mechanisms of abnormal steroid production in hyperfunctioning and non-hyperfunctioning adrenal tumors, we examined both the activities and amounts of steroidogenic cytochromes P450 in the tumor and non-tumor portions of these adrenals at the posttranslational (protein) level. Adrenals from 5 patients with primary aldosteronism, 5 with Cushing's syndrome, 1 with deoxycorticosterone (DOC)-producing adenoma, 10 with non-hyperfunctioning adrenal adenoma, and 5 subjects with normal control adrenals (obtained from patients with renal cell carcinoma) were used in our studies. Activities of P450scc, P45011 beta and P450aldo, and P450C21 and P-45017 alpha were assayed in a reconstituted enzyme system using 20 alpha-hydroxycholesterol, DOC, and progesterone, respectively, and the substrate and the extracted products were analyzed by HPLC. Enzyme amounts were determined by immunoblot analysis with anti-bovine P450scc, P45011 beta, and P450C21 IgG, and anti-porcine P45017 alpha IgG. Human P450aldo was only detected in the tumor portion of primary aldosteronism adrenals, with both activities and amounts of other P-450s similar to those in the non-tumor portion of primary aldosteronism and normal controls. In Cushing's syndrome, both activities and amounts of P45017 alpha and P450C21 were significantly increased in the tumor compared with those in the non-tumor portion of Cushing's syndrome and normal controls. In DOC-producing adenoma, both activities and amounts of P45017 alpha and P45011 beta in the tumor portion of the adenoma decreased compared with normal control, while those of other P450s were similar to normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792815 TI - Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis. AB - Glucocorticoid-remediable aldosteronism (GRA) is a hereditary cause of human hypertension in which aldosterone secretion is regulated by adrenocorticotropin (ACTH). A genetic mutation which causes GRA has recently been identified in our laboratory, a hybrid or chimeric gene fusing nucleotide sequences of the 11 beta hydroxylase and aldosterone synthase genes. The finding that these chimeric gene duplications are sensitive and specific markers for GRA allows for a simple, direct genetic test for this disorder. In preliminary studies, we found a wide range of blood pressure levels (including normotension) in affected GRA subjects. Studies to data indicate that this is not related to environmental factors such as sodium intake. Another possibility is that chimeric gene expression is variable, with low blood pressure subjects having reduced gene expression. However, the data have not demonstrated differences in steroid levels in subjects with severe versus mild hypertension. In fact, it is likely that the wide range in blood pressure levels in affected subjects involves interaction of other systems which control blood pressure. Preliminary data in two kindreds suggest that blood pressure levels are reciprocally related to levels of urinary kallikrein excretion, supporting the notion that GRA is a hypertension predisposing syndrome, with the resultant blood pressure the interaction of the gene mutation with other blood pressure regulatory systems. Although GRA is a mineralocorticoid excess state, as evidenced by profoundly suppressed levels of plasma renin activity, we have observed (contrary to the reported literature) that normokalemia is a typical finding. In one large normokalemic pedigree, preliminary findings indicate that these subjects have a normal capacity to excrete potassium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792816 TI - My engagement with steroids: a review. AB - In the course of my studies of patients with mineralocorticoid hypertensive disorders, unusual presentations led to unexpected findings, both clinically and in steroid etiologies and regulation. Unique circumstances permitted early studies in defining the autonomy of the aldosterone-producing adenoma. A chance referral brought the index case of 17 alpha-hydroxylase deficiency to the research center. New techniques were developed in unusual ways to measure the metabolites of deoxycorticosterone (DOC) using an anesthetic agent. Procedural delays were followed by the surreptitious transfer of a patient from one hospital to the research center after a benign DOC-secreting tumor had been removed. The delay of DOC and all 17-deoxysteroids to respond normally to ACTH stimulation suggested a possible second regulator of DOC. This observation led to studies that demonstrated divergent responses between DOC and cortisol in diverse conditions. An unexplained mineralocorticoid form of hypertension with suppression of renin and aldosterone, but normal DOC production, is seen in licorice intoxication. After licorice was discontinued we documented the delay in the recovery of the inhibited cortisol metabolism (14 days) and renin-angiotensin system (4 months). Licorice extract given to normal subjects on low sodium diets with and without ACTH suppression showed similar results. Other factors in licorice may thus be operative in terms of renin and aldosterone suppression. PMID- 7792817 TI - Rodent models for studying steroids and hypertension: from fetal development to cells in culture. AB - We have used several different approaches to study the role of steroids in hypertension, including rodent in vivo models, transgenic animals, and cell culture systems. Using the developing rodent fetus as a model for the ontogeny of regulation of glucocorticoid and mineralocorticoid synthesis, we found that in the developing rodent fetus, expression of both P450scc (cholesterol side chain cleavage) and P450c11 beta (11 beta-hydroxylase) mRNAs occur early, before there is complete organization of the fetal adrenal. Even after the zones of the adrenal are evident, the fetal adrenal still does not express the glomerulosa specific P450c11AS (aldosterone synthase) mRNA. Stimulating maternal adrenal mineralocorticoid or glucocorticoid synthesis does not affect accumulation of fetal adrenal steroidogenic mRNAs, suggesting that the rodent fetal adrenal may be somewhat transcriptionally quiescent in vivo. We also used two different transgenic rodent systems to study the roles of steroids in hypertension. Using promoter-directed tumorigenesis in transgenic mice, we created transgenic mice that expressed SV40 T antigen under control of the P450scc promoter. Massive adrenal tumors, but not gonadal tumors, developed in all transgenic mice, and cells from these tumors were easily cultured. Using a novel selection tactic, we obtained several adrenocortical cell lines which have distinct characteristics, suggesting they were locked into various stages of differentiation; both expression of steroidogenic mRNAs and the steroids synthesized differ among the lines. Regulation of steroid synthesis and mRNA abundance also varies among cell lines. Several cell lines also express mouse renin, and its synthesis, secretion, and mRNA abundance is also hormonally regulated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792818 TI - Functional studies of 11 beta-hydroxysteroid dehydrogenase. AB - 11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11-HSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the "short chain dehydrogenase" family. Using site-directed mutagenesis, it was demonstrated that two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Elimination of the amino terminus or the two glycosylation sites also destroys enzymatic activity. This may be due to actual disruption of enzymatic function or to effects on intracellular localization or stability of the enzyme. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11-HSD deficiency, did not reveal any mutations in the gene for this enzyme. There is substantial evidence for a second 11-HSD isozyme with distinct kinetic properties that is expressed in the renal distal tubule and possibly other sites of mineralocorticoid action. Apparent mineralocorticoid excess may involve this enzyme. PMID- 7792819 TI - Mineralocorticoid modulation of central control of blood pressure. AB - An association between mineralocorticoids and hypertension has been recognized for over 50 years, although the mechanisms involved are not entirely clear. In addition to the hypertension seen in cases of frank mineralocorticoid excess, such as in an aldosterone-producing adenoma, many essential hypertensive patients respond to treatments mitigating mineralocorticoid action, even though circulating levels of these steroids are within normal ranges. It has been a decade since David Bohr hypothesized that a center within the brain, probably in the AV3V area, was responsible for the orchestration of the multiple homeostatic mechanisms controlling blood pressure. It was proposed that the "set point" for such a center was dependent upon intracellular Ca + + and/or another ion content or transport across cell membranes, and was altered by mineralocorticoids and in some forms of genetic hypertension. The focus of this paper is the role of the central nervous system in mineralocorticoid hypertension. The importance of these data resides in the possibility that the central mechanisms involved in mineralocorticoid hypertension may also be operant in the pathogenesis of other forms of hypertension, as well as in the normal control of blood pressure. PMID- 7792820 TI - Differences in temperature-sensitive receptor binding of glucocorticoids in spontaneously hypertensive and normotensive Wistar-Kyoto rats. AB - Glucocorticoid receptor binding was compared in liver cytosol preparations from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using homologous displacement of [3H]dexamethasone. At 5 degrees C, there was no difference in receptor binding affinity or concentration between strains for dexamethasone, corticosterone or aldosterone. At 37 degrees C, affinity for dexamethasone was lower than at 5 degrees C for both rat strains and decreased with time. However, at this higher temperature, binding affinity in the SHR preparation was consistently higher than in the WKY preparation. The WKY preparation had a higher receptor concentration. The rate of dissociation of the [3H]dexamethasone-receptor complex prepared at 5 degrees C and then incubated at 37 degrees C was rapid but not different between strains. A possible explanation of these results is that the relationship of the heat shock proteins to the receptor heterocomplex is different between strains. Evidence exists of a genetic difference in Hsp 70 between SHR and WKY rats, although its cosegregation with blood pressure has not been established. PMID- 7792821 TI - Mechanisms of cortisol-induced hypertension in humans. AB - There is emerging evidence that cortisol plays a significantly greater role in human hypertension than previously thought. Apart from the well recognized role of cortisol in the hypertension of Cushing's syndrome, local cortisol excess has been recognized as responsible for rare forms of hypertension such as apparent mineralocorticoid excess and licorice abuse and more recently implicated in the hypertension of chronic renal failure, hypertension related to low birth weight and essential hypertension. Although cortisol-induced hypertension is characterized by sodium retention and volume expansion, studies with synthetic glucocorticoids or sodium restriction suggest that the hypertension is, to a substantial degree, independent of sodium and volume. Increase in cardiac output is not essential for cortisol-induced blood pressure rise but the precise role of increases in total or regional peripheral resistance as a primary mechanism has nto been determined. Increased pressor responsiveness, particularly to catechols, is a prominent feature but whether these changes are sufficient to account for the hypertension remains unclear. There is no evidence for increased sympathetic nervous activity as judged by measurements of plasma catcholamines, neuropeptide Y, or resting noradrenaline spillover rate. Responses to mental stress or maximal hand-grip are unchanged and baroreflex sensitivity is increased. Octreotide profoundly reduced the elevated plasma insulin concentrations seen with cortisol administration but had no effect on the rise in blood pressure. PMID- 7792822 TI - Long-term treatment of mineralocorticoid excess syndromes. AB - Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or beta-blockers, while 13 were switched to an amiloride/thiazide combination (+/- beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upset or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca++ channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792823 TI - Cortisol resistance and the guinea pig glucocorticoid receptor. AB - The guinea pig has been employed as a model to study the structure/function relationships of the glucocorticoid receptor (GR), and to determine the regions of the receptor important for binding hormone and antihormone. Guinea pigs have high levels of circulating cortisol and GR with a approximately 20-fold lower affinity for dexamethasone than mouse GR. Cloning and sequencing of guinea pig GR has identified 24 amino acid changes in the ligand-binding domain (LBD) compared to the human GR. By substituting the guinea pig GR LBD for the human LBD in a human GR expression vector we have shown in cotransfection studies that guinea pig GR LBD confers glucocorticoid resistance as observed in vivo. In initial studies guinea pig GR LBD appeared constitutively active; in subsequent studies to determine which of the 24 amino acid changes present in the guinea pig GR LBD conferred resistance, it became apparent that the guinea pig LBD (LBD delta), amplified by PCR for subcloning into the human GR expression vector, contained a single adenine deletion in the hinge region within ten bases of the PCR primer. This single base deletion resulted in a frameshift bringing a stop codon into frame one codon after the deletion. While this now clearly accounts for the observed constitutive activity, since it is known that C-terminally truncated steroid receptors exhibit constitutive activation such a truncation is more difficult to reconcile with the repeatedly demonstrable hormone dose-response curves obtained with this guinea pig GR LBD delta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792824 TI - Molecular genetic analysis of glucocorticoid signaling during mouse development. AB - Glucocorticoids are important in a number of developmental processes in mammals around birth. The pathway of gluconeogenesis is activated in liver shortly after birth due to the combined effects of glucocorticoids and glucagon. We have defined the essential cis-regulatory elements directing hormone-dependent liver specific expression of the gene for tyrosine aminotransferase, a key gluconeogenic enzyme. The hormone response elements synergize with cell-type specific elements. In the case of glucocorticoids, the glucocorticoid-dependent enhancer is composed of the glucocorticoid response element and binding sites for liver cell-enriched transcription factors, in particular hepatocyte nuclear factor-3. The dependence of the respective enhancer motifs on each other restricts the hormonal activation of the tyrosine aminotransferase gene in liver in response to a hormonal signal. To further understand the role of glucocorticoid signaling via the type II glucocorticoid receptor (GR) in the perinatal period and earlier during development, we have studied the expression of the mouse GR gene. Expression of the gene is controlled by at least three promoters, one of which is only active in T-lymphocytes. Expression of GR mRNA has been detected as early as day 9.5 of mouse development. To specifically address the role of glucocorticoid signaling via the GR during development, we have disrupted the GR gene by homologous recombination in mouse embryonic stem cells. The majority of GR mutants die shortly after birth and analysis so far has revealed defects in lung, liver, and adrenal function. PMID- 7792825 TI - The two faces of a steroid antagonist: when an antagonist isn't. AB - Activation of protein kinase A potentiates the transcriptional response mediated by the glucocorticoid receptor in responsive fibroblasts and in mammary carcinoma cells. This potentiation is ligand-dependent and occurs in responsive fibroblasts and in mammary carcinoma cells. This potentiation is ligand-dependent and occurs without detectable change in the phosphorylation of receptor. The transcriptional response to glucocorticoid or progestin agonists can be blocked by potent antagonists like RU 486. However, upon activation of protein kinase A, the antagonist action of RU 486 on both receptors is blunted. Indeed, RU 486 can itself activate transcription of a hormone-responsive promoter. The conditional agonist activity is observed with type II antagonists, those which recapitulate many of the early steps of ligand-dependent receptor activation, but not type I antagonists, which do not. These studies have now been extended to antimineralocorticoids. In COS-1 cells transfected with a mineralocorticoid receptor expression vector, treatment with 8-BromocAMP potentiates the response to the agonist aldosterone and elicits additional agonist activity in mineralocorticoid antagonists. A model is proposed wherein type II antagonist receptor complexes occupy receptor binding sites on the genome. The antagonist, however, fails to promote a receptor conformation that can interact productively with a coactivator mediating the communication between receptor and the basal transcription apparatus. Activation of protein kinase A results in the recruitment or activation of a coactivator that permits recovery of receptor mediated activation function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7792827 TI - Active-site-directed photoaffinity radioiodination of androgen-binding proteins. AB - Androgen-binding protein (ABP) in rat epididymal cytosol and sex hormone-binding globulin (SHBG) in rabbit serum and SHBG purified from human serum were active site-directed photoaffinity radiolabeled with 17 alpha-[(E)-2 [125I]iodoethenyl]androstan-4,6-dien-17 beta-ol-3-one ([125I]1). The interaction of this compound with binding components in epididymal cytosol was dependent on exposure of the mixture to ultraviolet light and on the duration of exposure. Photolysis in the presence of [125I]1 and 5 alpha-dihydrotestosterone (5 alpha DHT) resulted in a 40% inhibition of binding of [125I]1 to cytosolic components. These result indicate that, while [125I]1 interacted with 5 alpha-DHT binding sites, it also formed adducts with other sites. To characterize the labeled species, the photolysis mixture was subjected to electrophoresis under denaturing and reducing conditions. Autoradiography of the gel revealed that ABP and SHBG were labeled with [125I]1, but in cytosol and serum, higher and lower molecular weight components were also labeled. Purified SHBG was labeled, but no labeled contaminating protein was detected. The presence of 5 alpha-DHT completely inhibited [125I]1 photolabeling of human and rabbit SHBG and of ABP. However, in cytosol, the presence of 5 alpha-DHT also eliminated photolabeling to a component that may be albumin, but 5 alpha-DHT did not affect [125I]1 photolabeling of other contaminating proteins in cytosol. Thus, while [125I]1 is an effective photoaffinity radiolabel for ABP and SHBG, the observation that it also photolabels other proteins limits its practical use to the radiolabeling of purified ABP and SHBG preparations. PMID- 7792826 TI - Synthesis of (17R)- and (17S)-17-hydroxy-14, 15-secoandrost-4-en-15-yn-3-one and the X-ray crystal structure of the (17S)-diastereomer. AB - (17R,S)-17-Hydroxy-14,15-secoandrost-4-en-15-yn-3-one has been shown previously to be a mechanism-based inactivator of rat liver 3 alpha-hydroxysteroid dehydrogenase. This manuscript describes the synthesis of this diastereomeric 14,15-secosteroid from [2S-2 alpha,4a alpha,4b beta,10a beta)]- 1,2,3,4a,4b,7,9,10,10a-decahydro-2,4b-dimethyl-7-oxo-2-phenanth renecarboxylic acid methyl ester. The separation of this diastereomeric 14,15-secosteroid into (17R)- and (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was accomplished by HPLC separation of the (S)-1-[(4-methylphenyl)sulphonyl]-2 pyrrolidinecarboxylate derivatives on a silica column. The crystal structure of (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was then solved by X-ray diffraction analysis to establish unambiguously the absolute configuration of the diastereomeric 14,15-secosteroid. PMID- 7792828 TI - Crystal structure of doisynolic acid and the structure of other products formed during its synthesis. AB - The crystal structure of the D-seco-estrogen doisynolic acid shows it to have the natural S configuration at the position derived from C-14 in estrone. Two major by-products during the synthesis of doisynolic acid from estrone are shown to be dimeric steroids. One is an aldol condensation product, and the other appears to arise from an alkaline cleavage of the aldol product. PMID- 7792829 TI - 19-Acetylenic-deoxycorticosterone inhibits 19-hydroxylase and 11 beta-hydroxylase activities in dispersed bovine zona fasciculata cells. AB - 19-Acetylenic-deoxycorticosterone (19-A-DOC) is believed to be a competitive irreversible inhibitor of the synthesis of 19-nor-deoxycorticosterone (19-nor DOC), a potent mineralocorticoid implicated in some forms of human and animal hypertension. It has been shown to inactivate 11 beta/19-hydroxylase in hamster adrenal mitochondria. Dispersed bovine zona fasciculata cells were incubated for one hour with 1.5 x 10(-8) M ACTH and 0, 1, 10, or 100 microM 19-A-DOC and tritiated deoxycorticosterone (DOC) substrate. Steroids were separated using two sequential thin-layer chromatography systems and their tritium content was counted and corrected for recovery. The 19-A-DOC decreased synthesis of 19 hydroxydeoxycorticosterone, the precursor of 19-nor-DOC. The inhibitor also impaired 11-hydroxylation of DOC to form corticosterone. The data suggest that 19 A-DOC is an effective inhibitor of 11 beta/19-hydroxylase activity in dispersed bovine adrenal cells. PMID- 7792830 TI - Synthesis of 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione and 21-hydroxy-6,19 oxidopregn-4-ene-3,20-dione. AB - The 21-hydroxy analogues of 11,19-oxidoprogesterone and 6,19-oxidoprogesterone have been synthesized from readily available materials. Hydroxylation at C-21 was effected with iodosobenzene (from phenyliodosodiacetate and methanolic potassium hydroxide) on a 20-ketopregnane. For the 11,19-oxido derivative, the hydroxylation was carried out on a precursor containing the oxido-bridge. This approach was not adequate for the 6,19-oxido steroid due to the very low yields encountered; hence in the latter case the order of introduction of the C-21 functionality and the oxido-bridge was reversed. PMID- 7792831 TI - Stimulation of progesterone secretion in dispersed cells of rat corpora lutea by antioxidants. AB - Antioxidants were used to investigate the role of free radicals in control of luteal steroidogenesis. Corpora lutea from pseudopregnant rats were enzymatically dispersed, the cells were incubated with antioxidants, and progesterone production was measured. Addition of the antioxidants nordihydroguaiaretic acid (NDGA), butylated hydroxytoluene (BHT), and the gonadotropin luteinizing hormone (LH) resulted in a dose-dependent increase in progesterone secretion. However, the response pattern to these treatments differed with the age of the corpora lutea, and unlike LH neither NDGA nor BHT treatment resulted in an increase in the intracellular second messenger cAMP. Nevertheless, LH and antioxidant-induced progesterone stimulation could be blocked by the addition of either aminoglutethimide or ketoconazole, cytochrome P450 side-chain cleavage (cytochrome P450 SCC) enzyme inhibitors, which prevent the conversion of cholesterol to pregnenolone and thus block steroid hormone synthesis. Also, unlike exposure to LH, exposure to antioxidants resulted in an additional increase in progesterone production in luteal tissue saturated with 25 hydroxycholesterol, a soluble cholesterol analog which serves as a substrate for cytochrome P450 SCC. This study suggests that the site of antioxidant action in affecting progesterone secretion may be at the cytochrome P450 SCC enzyme. Based on these results and on studies in other steroid hormone-producing cells, it appears that free radicals may be involved in regulating synthesis by modulating activity of cytochrome P450 SCC enzyme in rat luteal tissue. PMID- 7792833 TI - A method for measurement of free testosterone in premenopausal women involving equilibrium dialysis, chromatography, and radioimmunoassay. AB - A three-step procedure to evaluate the quantity of true free testosterone in female serum was established. Unbound and bound testosterone were first separated by equilibrium dialysis using undiluted serum. Testosterone in dialysate was extracted and separated from cross-reactive steroids by column chromatography and finally quantified with a sensitive radioimmunoassay. The detection limit of the radioimmunoassay was 2.7 pmol/L and the detection limit of the whole method was 6 pmol/L. The intra-assay coefficients of variation of the method were 20.6%, 16.8%, and 9.5% for free testosterone concentrations 12.0 pmol/L, 21.4 pmol/L, and 31.4 pmol/L, respectively. The interassay coefficients of variation were 26.3% and 14.8% for free testosterone concentrations 10.4 pmol/L and 21.3 pmol/L, respectively. Serum free testosterone concentrations were determined in 27 regularly menstruating control women. The mean concentration of actual free testosterone was 10.0 +/- 4.9 pmol/L (mean +/- SD, range from below 6 to 19 pmol/L, n = 27). PMID- 7792832 TI - Synthesis of 15 alpha-hydroxyestrogen 15-N-acetylglucosaminides. AB - The synthesis of 15-N-acetylglucosaminides of 15 alpha-hydroxyesterone, 15 alpha hydroxyestradiol, and 15 alpha-hydroxyestriol (estetrol) is described. The latter two were prepared by condensation of 2-acetamido-1 alpha-chloro-1,2-dideoxy-3,4,6 trio-O-acetyl-D-glucopyranose with appropriately protected 15 alpha hydroxyestrogens by the Koenigs-Knorr reaction employing cadmium carbonate as a catalyst. Subsequent removal of protecting groups with methanolic potassium hydroxide provided the desired conjugates. 15 alpha-Hydroxyestrone 15-N acetylglucosaminide was synthesized from the corresponding 15 alpha hydroxyestradiol derivative by Jones oxidation followed by brief alkaline hydrolysis. These conjugates underwent enzymatic hydrolysis with beta-N acetylglucosaminidase from Jack beans to produce 15 alpha-hydroxyestrogens. PMID- 7792834 TI - A convenient synthesis of 7 alpha-hydroxycholest-4-en-3-one by the hydroxypropyl beta-cyclodextrin-facilitated cholesterol oxidase oxidation of 3 beta,7 alpha cholest-5-ene-3,7-diol. AB - The initial biosynthetic conversions of cholesterol to the bile acids involve sequential 7 alpha-hydroxylation (catalyzed by cholesterol 7 alpha-hydroxylase) followed by C-3 oxidation and concomitant double bond migration (to a delta 4 configuration, catalyzed by 3 beta-delta 5-C27-steroid oxidoreductase) to provide 7 alpha-hydroxycholest-4-en-3-one. A straightforward, and economical, preparation (on a 0.1 g scale) of this pivotal biosynthetic intermediate has been devised. Reduction of 3 beta-(benzoyloxy)-cholest-5-en-7-one with LiB(sec-butyl)3H provided a 4:1 mixture, respectively, of the 7 alpha- and 7 beta-hydroxy diastereomers, which were separated chromatographically. Solvolytic removal of the C-3 benzoyl group gave 3 beta,7 alpha-cholest-5-ene-3,7-diol. A suspension of the 1:1 (v/v) complex (formed by mutual dissolution in MeOH, followed by evaporation of the solvent) of this diol with hydroxypropyl-beta-cyclodextrin, at a concentration of 1 mg mL-1 (in neutral phosphate buffer), was converted by Brevibacterium sp cholesterol oxidase (0.25 U mg-1 of substrate) and catalase (70 U mg-1 of substrate, to recover O2 from the H2O2 produced by the enzymatic oxidation) to a suspension of 7 alpha-hydroxycholest-4-en-3-one and the hydroxypropyl-beta-cyclodextrin. The yield for the enzymatic conversion was in excess of 90%. A much poorer and less reproducible yield (< 20%) was seen in the absence of the hydroxypropyl-beta-cyclodextrin. Routine extraction of this aqueous suspension, and chromatographic purification (85:15 CHCl3/acetone v/v on silica) of the residue, gave pure 7 alpha-hydroxycholest-4-en-3-one in 68% isolated yield. This route is a significant improvement, in terms of reaction scale and convenience, over the previous procedures for the preparation of this steroid. PMID- 7792836 TI - Estrone sulfate analogs as estrone sulfatase inhibitors. AB - The high serum concentration of estrone sulfate and the presence of estrone sulfatase in breast tumors constitute an important mechanism of local synthesis of estrogens in the tissue. Thus, inhibitors of estrone sulfatase may be effective in the treatment of estrogen-dependent breast cancer. In this study, we synthesized several isostructural analogs of estrone sulfate (estrone-3 methylsulfonate, estrone phosphate, 3-desoxyestradiol-3-methylenesulfonate, and 3 desoxyestrone-3-methylenesulfonate) and tested them on human placental sterylsulfatase. The results were (i) The Ki of 3-desoxyestrone-3 methylenesulfonate 12 and 3-desoxyestradiol-3-methylenesulfonate 7 are more than 100-fold higher than the Ki or KM values for estrone sulfate, (ii) As compared to estrone sulfate, the Ki value for estrone-3-methylsulfonate 2 is about 30-fold higher, while estrone phosphate 3 is bound by the sulfatase with roughly the same affinity as estrone sulfate. The results shed some light on the electronical and sterical requirements for high affinity binding to the enzyme. PMID- 7792835 TI - Direct determination of human urinary cortisol metabolites by HPLC/CRIMS. AB - Feasibility of using high performance liquid chromatographic input to the chemical reaction interface mass spectrometry system was assessed by measuring the profile of hydrolyzed urinary metabolites of [9,12,12-2H3] cortisol in six human subjects with no preparation other than hydrolysis and solid phase extraction. Relative amounts of tetrahydrocortisol, tetrahydrocortisone, and cortolones (as the sum of alpha- and beta-) were 0.417 +/- 0.047, 0.523 +/- 0.036 and 0.059 +/- 0.019, respectively. The constant reproducibility of the measurements coupled with a profile consistent with that observed by other workers shows that the technique represents an important tool in the determination of metabolites of endogenous molecules. PMID- 7792837 TI - Proceedings of the Vth International Alexis Carrel Conference. Genesis, prevention, diagnosis and treatment of chronic rejection, obliterative bronchiolitis and graft vessel disease after organ transplantation. Munich, Germany, June 22-24, 1994. PMID- 7792838 TI - Graft vasculopathy among recipients of heart transplantation during the first 12 years of life. The Pediatric Heart Transplant Group. PMID- 7792840 TI - Cardiac allograft vasculopathy. PMID- 7792839 TI - Does donor and recipient sex influence the development of cardiac allograft vasculopathy? PMID- 7792842 TI - The role of PTCA in the management of focal critical lesions in transplant coronary artery disease. PMID- 7792841 TI - Prevention and treatment of graft vessel disease after heart transplantation. PMID- 7792844 TI - Coronary artery disease in cardiac allografts: association with depleted arteriolar tissue plasminogen activator. PMID- 7792843 TI - Coronary artery disease in cardiac allografts: association with arteriolar endothelial HLA-DR and ICAM-1 antigens. PMID- 7792846 TI - The histological grade of rejection does not relate to intracardiac pressures. PMID- 7792845 TI - Coronary artery disease in cardiac allografts: association with arterial antithrombin. PMID- 7792847 TI - Heparin-induced extracorporeal low-density-lipoprotein plasmapheresis (HELP) and its use in heart transplant patients with severe hypercholesterolemia. PMID- 7792848 TI - Is a reduction of graft vessel disease by maximal treatment of hypercholesterolemia after heart transplantation possible? PMID- 7792850 TI - Enhanced monocyte transendothelial migration into graft-specific vessel wall cocultures after cardiac transplantation. PMID- 7792853 TI - Cyclophosphamide as an adjunct to maintenance immunosuppression in cardiac transplantation. PMID- 7792849 TI - Impaired renal function but not high cyclosporine levels determines increased endothelin plasma levels after heart transplantation. PMID- 7792851 TI - Acute rejection and cytomegalovirus infection: correlation with cardiac allograft vasculopathy. PMID- 7792852 TI - Evaluation of cytomegalovirus-polymerase chain reaction in graft dysfunction after heart transplantation. PMID- 7792854 TI - Measurement of microalbumin and retinol binding protein in cardiac and lung transplant recipients. PMID- 7792855 TI - Dobutamine stress echocardiography for detection of transplant coronary vasculopathy: comparison with angiography and intracoronary ultrasound. PMID- 7792856 TI - Qualitative and quantitative assessment of cardiac allograft vasculopathy by intravascular ultrasound. PMID- 7792858 TI - Influence of acute cellular rejection on long-term left ventricular systolic function after orthotopic heart transplantation. PMID- 7792857 TI - Influence of HLA compatibility on the incidence of cardiac allograft vasculopathy after heart transplantation. PMID- 7792859 TI - Cardiac changes during acute allograft rejection: evaluation by serial echocardiographic measurements over a 5-year follow-up period. PMID- 7792860 TI - Intramyocardial electrograms for monitoring of allograft rejection after heart transplantation. PMID- 7792861 TI - Role of intracoronary ultrasound for the diagnosis of cardiac allograft vasculopathy. PMID- 7792862 TI - Prophylactic photopheresis and effect on graft atherosclerosis in cardiac transplantation. PMID- 7792863 TI - Living-related lobar transplantation: recipient outcome and early rejection patterns. PMID- 7792864 TI - Human lung preservation with Euro-Collins solution: early postoperative transplant function correlates with ultrastructural alterations of the contralateral donor lung. PMID- 7792866 TI - Videothoracoscopic wedge resection of the lung for the diagnosis of acute rejection in lung transplant recipients. PMID- 7792865 TI - Monitoring of lung rejection with home spirometry. PMID- 7792867 TI - Rejection and nonrejection related forms of bronchiolitis obliterans: morphologic terms or clinico-pathological entities? PMID- 7792868 TI - Gastro-esophageal reflux as cause of obliterative bronchiolitis: a case report. PMID- 7792869 TI - Evaluation of the development of bronchiolitis obliterans syndrome in single lung recipients by assessment of transplant FEV1 with 133-XE radiospirometry. PMID- 7792870 TI - Pathology of graft vascular disease after heart and heart-lung transplantation and its relationship to obliterative bronchiolitis. PMID- 7792871 TI - Graft vessel disease and obliterative bronchiolitis after heart/lung transplantation in children. PMID- 7792872 TI - Significance of graft coronary artery disease in heart-lung transplant recipients. PMID- 7792873 TI - Behavior of serum cytokine levels and peripheral lymphocyte subsets after H-LTx. PMID- 7792874 TI - Cytokine and cytokine-receptor profiles after liver and heart transplantation. PMID- 7792875 TI - Risk factors for chronic transplant failure after kidney transplantation. PMID- 7792876 TI - Evaluation of chronic allograft reaction in kidneys by interphase cytogenetics with centromere-specific DNA probes and immunocytochemistry with regard to distribution of donor and recipient cells. PMID- 7792877 TI - The role of lipoprotein abnormalities in chronic vascular rejection after kidney transplantation. PMID- 7792879 TI - Haemodynamic changes in kidney graft chronic rejection evaluated by echo-colour Doppler flowmetry. PMID- 7792878 TI - Chronic rejection in kidney transplant patients receiving cytomegalovirus prophylaxis with acyclovir. PMID- 7792880 TI - Tc-DTPA scintigraphy in renal allograft rejection. PMID- 7792882 TI - Manifestation of metabolic risk factors after renal transplantation: I: Association with long-term allograft function. PMID- 7792881 TI - Cell surface phenotype and in vitro donor antigen-specific hyporesponsiveness in recipients of living donor kidney transplants. PMID- 7792883 TI - Manifestation of metabolic risk factors after renal transplantation: II. Impact of maintenance therapy. PMID- 7792885 TI - Impact of lipids on progression and regression of atherosclerosis. PMID- 7792884 TI - Manifestation of metabolic risk factors after renal transplantation: III. Impact on cerebrocardiovascular complications. PMID- 7792886 TI - Early proliferation of medial smooth muscle cells in coronary arteries of rabbit cardiac allografts during immunosuppression with cyclosporine A. PMID- 7792887 TI - Role of growth factors in graft vessel disease. PMID- 7792889 TI - Gender effects on graft myointimal hyperplasia. PMID- 7792888 TI - Studies in experimental models of chronic rejection: use of rapamycin (sirolimus) and isoxazole derivatives (leflunomide and its analogue) for the suppression of graft vascular disease and obliterative bronchiolitis. PMID- 7792890 TI - Nitric oxide and its role in transplantation. PMID- 7792892 TI - Pathogenetic studies in a rat cardiac model of chronic vascular rejection. PMID- 7792891 TI - Transplant vasculopathy in rat heart transplantation: a morphologic chameleon determined by antigen-dependent and -independent factors. PMID- 7792893 TI - Pathological alterations in graft vessels after major histocompatibility complex incompatible heterotopic heart transplantation: a rat model. PMID- 7792894 TI - Assessment of troponin-T for detection of cardiac rejection in a rat model. PMID- 7792895 TI - Assessment of cardiac rejection and immunosuppression by magnetic resonance imaging and spectroscopy. PMID- 7792896 TI - Neurohumoral regulation of endothelin release by opioid and natriuretic peptides. PMID- 7792897 TI - Enhanced endothelin-1 urine excretion in patients with graft arteriosclerosis after heart transplantation. PMID- 7792899 TI - Chronic rejection in cryopreserved aortic allografts. PMID- 7792900 TI - Evidence that the degeneration of heart valve grafts is immunologic. PMID- 7792898 TI - Modulation of inflammatory activation pathways in the Lewis-to-F-344 rat chronic cardiac rejection model. PMID- 7792901 TI - Preformed natural antibodies: their impact on contractile activity of cardiomyocytes. PMID- 7792902 TI - Intrathymic injection of donor splenocytes plus systemic antilymphocyte serum or antilymphocyte serum alone prolongs cardiac allograft survival and inhibits graft arteriosclerosis in the Lewis-to-F344 chronic rejection model. PMID- 7792903 TI - Chronic vascular changes and obliterative bronchiolitis in an experimental porcine lung transplantation model. PMID- 7792904 TI - Graft-infiltrating cells in rat lung allograft with late airway damage. PMID- 7792906 TI - Experimental models of chronic renal allograft rejection. PMID- 7792905 TI - Thoughts on the immunobiology of chronic allograft rejection. PMID- 7792907 TI - Experimental studies of the pathogenesis of chronic allograft rejection. PMID- 7792908 TI - Characteristic signs of chronic allograft rejection can be observed in mechanically manipulated naive rat kidneys over the long-term. PMID- 7792910 TI - Graft survival after corneal transplantation: role of factors with the potential for recipient presensitisation. The Australian Corneal Graft Registry (ACGR). PMID- 7792911 TI - The 12th scientific meeting of the Transplantation Society of Australia and New Zealand. 20-22 April 1994. PMID- 7792912 TI - Covert presensitization to HLA antigens in parous heart and lung transplant recipients may predispose to early allograft rejection. PMID- 7792909 TI - Growth hormone and insulin-like growth factor-I: a suggested role in renal transplantation and graft vessel disease. PMID- 7792913 TI - Renal transplantation in infants and very small children: 3-year experience in patients treated with triple immunosuppression including cyclosporine. PMID- 7792914 TI - Liver transplantation for alcoholic cirrhosis: outcomes and difficulties in patient selection. PMID- 7792915 TI - Cardiac transplantation in patients over 60 years. PMID- 7792916 TI - Hyperlipidemia in renal transplant recipients: does it matter and can we treat it? PMID- 7792917 TI - Twenty and 25 years survival after cadaveric renal transplantation. PMID- 7792918 TI - Systemic immune response in rejection and tolerance of rat liver allografts. PMID- 7792920 TI - Infiltrating cells in mouse cardiac allografts after anti-CD4 monoclonal antibody treatment. PMID- 7792919 TI - Comparison of immune changes in rejecting rat cardiac allografts with tolerant cardiac allografts secondary to liver grafts. PMID- 7792921 TI - Endothelial cell activation and cytokine expression during acute human cardiac allograft rejection. PMID- 7792923 TI - Neonatal transfer of allogeneic thymic macrophages prevents autoimmunity in nonobese diabetic mice. PMID- 7792922 TI - Prevention of both rejection and recurrence of autoimmune disease in the NOD/Lt mouse following segmental pancreas transplantation. AB - In the NOD/Lt recipient mice, disease recurrence in untreated isografts was extremely rapid (median less than 10 days) compared to the rejection of an untreated BALB/c pancreas graft in a CBA mouse (median 26 days). This would be expected since disease recurrence is a secondary response in diabetic mice with lymphocytes primed to respond to the beta-cell autoantigen. The median survival time for the untreated CBA to NOD/Lt pancreas graft falls, as expected, between these two survival times (median 20 days). Although anti-CD4 and/or anti-CD8 were effective in delaying or stopping autoimmune disease recurrence and rejection in the separate models, they were unsuccessful in significantly altering survival times in the combined model, despite using 2-mg doses and dual therapy. Similar doses of anti-CD4 have failed to prevent islet allograft rejection in NOD/Lt mice. Long-term dual treatment may be required to inactivate CD4+ and CD8+ T cells in the NOD/Lt mouse to prevent both autoimmune disease recurrence and rejection. NOD/Lt recipients will require greater immunosuppression to prevent rejection-autoimmune disease recurrence will be easier to prevent. This study shows the value of using NOD/Lt mice, with naturally occurring type 1 diabetes, for assessment of immunosuppressive therapy to prevent failure of pancreas transplants. PMID- 7792924 TI - Construction of CD46 minigenes for the production of transgenic mice. PMID- 7792925 TI - Xenotransplantation of fetal pig pancreas and reversal of diabetes in spontaneously diabetic NOD mice. PMID- 7792926 TI - Effect of anti-CD4 monoclonal antibody on survival of xenografted human fetal pancreas. PMID- 7792927 TI - Effect of anti-CD4, anti-NC, and anti-NK monoclonal antibody on the survival of cardiac xenografts and allografts in mice. PMID- 7792928 TI - Serum uric acid and liver transplantation. PMID- 7792929 TI - Subjective assessment of donor liver quality. PMID- 7792930 TI - 5-HT2 receptor subtypes: a family re-united? AB - The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5 HT receptor subtype. The strong functional union of this family is reflected in the paucity of ligands that will discriminate between its subtypes and prompts some re-evaluation of the activities of compounds which may now be regarded as nonselective for the receptor subtypes in this class. In this article, Gordon Baxter and colleagues examine the pharmacology of both officially recognized and atypical 5-HT2 receptor subtypes. A number of novel selective agents are highlighted, some of which may prove useful for 5-HT2 receptor classification and, ultimately, clarify the mechanistic basis for current and future therapeutic strategies which target this receptor family. PMID- 7792931 TI - Multiple actions of somatostatin in neoplastic disease. AB - The role played by the neuropeptide somatostatin, also known as somatotropin release inhibitory factor (SRIF), in human cancer is not well understood. Recent investigations involving somatostatin receptors in normal and neoplastic human tissues suggest that the action is complex and involves both direct and indirect mechanisms. In this article, Jean-Claude Reubi and Jean Laissue describe the variety of biological mechanisms involved in neoplasia that are associated with somatostatin, and illustrate the therapeutic potential and present limitations of somatostatin analogues. PMID- 7792932 TI - Melatonin comes of age? PMID- 7792933 TI - Receptor state and ligand efficacy. PMID- 7792935 TI - Superficial buffer barrier function of smooth muscle sarcoplasmic reticulum. AB - In smooth muscle the superficial sarcoplasmic reticulum accumulates a portion of the Ca2+ that enters cells through the plasmalemma and thus functions as a buffer barrier to Ca2+ entry into the myoplasm (superficial buffer barrier or SBB). In this review Cornelis van Breemen, Qian Chen and Ismail Laher summarize experimental support for the SBB, and discuss data indicating that: (1) contraction is related more to the rate than extent of Ca2+ entry; (2) refilling of sarcoplasmic reticulum from the extracellular space is mediated by Ca2+ influx and Ca2+ pumping by the sarcoplasmic reticulum Ca2+ pump; (3) the superficial sarcoplasmic reticulum unloads Ca2+ to the extracellular space by a multi step process that involves sequentially the opening of Ca2+ and inositol 1,4,5 trisphosphate [Ins(1,4,5,)P3] sensitive channels and Ca2+ extrusion by Na(+)-Ca2+ exchange; (4) the SBB generates a peripheral Ca2+ gradient; (5) Ca(2+)-mobilizing receptor agonists generate Ins(1,4,5)P3 which short circuits the SBB to increase the effectiveness of Ca2+ influx in raising [Ca2+]i and consequently increase smooth muscle contraction. A physiologically regulated SBB is thought to enhance the informational content of Ca2+ signalling and support variable reduction of smooth muscle tone. Pharmacological modulation of Ca2+ transport in the superficial sarcoplasmic reticulum therefore presents an alternative means of controlling smooth muscle tone dependent on Ca2+ entry. PMID- 7792934 TI - Classification and nomenclature of somatostatin receptors. AB - There is considerable controversy about the classification and nomenclature of somatostatin receptors. To date, five distinct receptor genes have been cloned and named chronologically according to their respective publication dates, but two were unfortunately given the same appellation (SSTR4). Consensually, a nomenclature for the recombinant receptors has been agreed according to IUPHAR guidelines (sst1, sst2, sst3, sst4, and sst5). However, a more informative classification is to be preferred for the future, employing all classification criteria in an integrated scheme. It is already apparent that the five recombinant receptors fall into two classes or groups, on the basis of not only structure but also pharmacological characteristics. One class (already referred to by some as SRIF1) appears to comprise sst2, sst3 and sst5 receptor subtypes. The other class (SRIF2) appears to comprise the other two recombinant receptor subtypes (sst1 and sst4). This promising approach is discussed but it is acknowledged that much more data from endogenous receptors in whole tissues are needed before further recommendations on somatostatin receptor nomenclature can be made. PMID- 7792936 TI - [A comparison of the differentiation of tumor cells and of the epithelium of the gastric mucosa in cancer]. AB - The correlation between differentiation of tumor cells in different directions (toward the foveolate epithelium or glandular epithelium in stomach, or small and large intestine epithelium, or endocrine cells) and the state of gastric mucosa (differentiation of its cells in direction of foveolate epithelium or glandular epithelium (hypoplasia of corresponding epithelium), or appearance of focals of metaplasia in small or large intestines, or pronounced hyperplasia of endocrine cells) was revealed in most cases of gastric cancer. The other of the disease did not reveal such correlation. PMID- 7792937 TI - [The effect of thyroid and gonadal hormones on the chromosomal integrity of liver cells]. AB - The materials presented as well as the data of the author's previous investigations indicate different cytogenetic importance of the basic hormones of the thyroid and sexual glands (thyroxine, testosterone, and estradiol) when they are used in physiologic doses. Thyroxine possesses mutagenic and antimutagenic properties, testosterone possesses only mutagenic ones, while estradiol has no effect on chromosome integrity. PMID- 7792938 TI - [The polymorphic BsuRI restriction site of the swine growth hormone gene]. AB - Restriction fragment length polymorphism of the gene of the growth hormone was investigated in Big White and Mirgorod pigs. A polymorphous BsuRI restriction site was found within an amplified gene-region near 5-end. It was localized within the first intron, 1.6 b.p. higher than exon 2 was. Homozygous as well as heterozygous animals according to variants of the gene were found. PMID- 7792940 TI - [The intrabreed genotypic variability of Ukrainian beef cattle]. AB - The intrabreed genotype heterogeneity in Ukrainian beef cattle was studied for 13 genetic-biochemical systems in relation to the differentiation of animals by sex, age color, birth weight and the weight increase during the first 6 months of life. The greatest value of genetic distance was revealed between animal groups, distinguished by the weight increase. The locus of purine nucleoside phosphorylase greatly contribute to this genetic differentiation. PMID- 7792939 TI - [Protein polymorphism in the crossbred progeny of Simmental and Red-and-White Holsteins]. AB - The analysis of the genetic structure at 12 genetic-biochemical systems of pure parental breeds and their mixed offspring was carried out. The genetic structure of the mixed offspring was also investigated in relation with their differences in milk productivity. Locus-specific peculiarities of reorganization of the gene pool in the process of obtaining mixed offspring were described. Some genetic biochemical systems involved in differentiation of groups of animals with respect to characteristics of milk production were revealed. PMID- 7792941 TI - [The detection and study of mitomycin C-induced mutational changes in stable lines of Drosophila melanogaster]. AB - The influence of mitomycin C on the genetic stability of Drosophila laboratory lines was investigated. This mutagen caused one-locus and multi-loci mutations with high frequencies (approximately 10(-2), 10(-3)) in the first and the second generations. It is locus-specific mutagenesis. In situ hybridization experiments indicated the existence of primary and new sites of location of mobile genetic elements mdg 1, mdg 2, mdg 4. This instability was caused by activation of transposition and recombination. PMID- 7792942 TI - [The morphofunctional heterogeneity between peritoneal and alveolar macrophages in their biogenic amine content: the effect of their presence or absence in the microenvironment of mast cells]. AB - Peritoneal macrophages differ from alveolar ones in biogenic amine content: peritoneal macrophages contain smaller amounts of histamine and serotonin. When activated, alveolar macrophages release biogenic amines, whereas in peritoneal macrophages stimulators of macrophage activity induce the increase in amine content. This may be due to the presence of mast cells in their microenvironment macrophage activity. PMID- 7792943 TI - [The markers of cells and other structures in the mammalian epiphysis cerebri]. AB - The information about pineal markers obtained mainly by the light and electron microscopic immunocytochemical and cytochemical methods is reviewed. The main attention is focused on the distribution of neuroglial and photoreceptor markers in different pineal cells and other pineal structures. Besides, the data on ultrastructural location of calcium and calcium-bound proteins (calbindins) in pineal tissues are presented. The main current trends of the development of this kind of research and possibilities to apply the results obtained for diagnostic purposes (oncomorphology etc.) are briefly discussed. PMID- 7792944 TI - [The mononuclear and multinuclear cells of tissue resorption and their functional characteristics]. AB - Mononuclear and multinuclear chondroclasts as well as osteoclasts and their involvement into the processes of replacement of provisional cartilaginous skeleton by definitive bony one were cytogenetically studied during ontogenesis of terrestrial vertebrates (amphibians, reptiles, birds, and mammals). It was detected that mononuclear and multinuclear clastic cells were distinctive morpho functional forms. The former are capable to resorb only non-calcified hyaline cartilage, the latter are capable to resorb only calcified tissues (cartilage, bone). The mechanisms of tissue resorption performed by these cells are discussed. PMID- 7792945 TI - Society for ultrastructural pathology 1994 pathologist-in-training award. PMID- 7792946 TI - Proliferative activity of synovial sarcoma: an immunohistochemical evaluation of Ki-67 labeling indices of 52 primary and recurrent tumors. AB - The relationship between cell differentiation and proliferation in biphasic synovial sarcoma (BSS) and the connection between the two components of these tumors and monophasic synovial sarcoma (MSS) are still unknown. In this study we specifically compared the Ki-67 labeling indices (Ki-67-LI) in the solid/glandular and spindle cell components of primary BSS (n = 8) as well as the values thus obtained in primary BSS both outside clear-cut biphasic areas (n = 7) and in primary MSS (n = 23). We also compare the Ki-67-LI of primary tumors (seven BSS, seven MSS) and their respective first recurrences. We observed that the cells of the solid/glandular component of BSS proliferate significantly faster (p = 0.007) than those of spindle cell areas. No significantly different Ki-67-LI were observed in the comparison of the solid/glandular areas of BSS with the spindle/epithelioid component of BSS without clear-cut biphasia and MSS. No significant differences of Ki-67-LI were observed in the comparison of primary tumors of both subtypes with their respective first recurrences. The implications of the low proliferative activity of the spindle cell component of BSS exhibiting clear-cut biphasia, which was also confirmed in a concurrent study using anti proliferating cell nuclear antigen/Cyclin PC10, remains to be clarified. PMID- 7792948 TI - Abnormal melanosomes: ultrastructural markers of melanocytic atypia. AB - To identify possible ultrastructural markers of melanocytic atypia, a quantitative ultrastructural study was made of melanocytes found at the dermal epidermal boundary of normal skin and in benign, premalignant, and malignant melanocytic lesions. There was a significant increase (p < 0.05) in the number of melanosomes per melanocyte in the premalignant and malignant lesions compared with the number observed in the benign lesions. There was a significantly higher number (p < 0.05) of abnormal melanosomes (with irregularities in the laminar matrix or with a granular or clumpy matrix) in the premalignant and malignant lesions, which suggests that the presence of a high percentage of abnormal melanosomes might act as a useful ultrastructural marker in the diagnosis of melanocytic atypia. PMID- 7792947 TI - Ultrastructure of epidermis of mice with chronic proliferative dermatitis. AB - C57BL/Ka mice with chronic proliferative dermatitis (cpdm/cpdm) develop chronic persistent skin lesions characterized by epidermal hyperplasia, infiltration by granulocytes and macrophages, and vascular dilatation. Similar lesions are present in other orthokeratotic epithelia in affected mice, in particular the esophagus and forestomach. Here, we report on further characterization of epidermal hyperplasia and the granulocytes. Keratinocytes of lesional skin, but not of normal skin, show round and electron-dense mitochondrial inclusions that are present in all layers of the epidermis. Similar inclusions are also present in the esophagus and forestomach of affected mice. There appears to be a direct relation between the presence of intramitochondrial inclusions and epidermal hyperplasia in the mouse. Furthermore, the presence of keratinocyte-derived apoptotic bodies in the epidermis, esophagus, and forestomach was frequently observed in the lesions, which is consistent with previous light microscopic observations of single cell death of keratinocytes. The granulocytes present in the skin, esophagus, and forestomach were mainly eosinophils. There were widespread gaps observed in the lamina densa in the epidermis that were mostly directly associated with dermal or epidermal eosinophils. This type of gap is also observed in psoriasiform diseases in humans. This electron microscopic study demonstrated that this mouse model should be useful to screen potential therapeutic strategies for psoriasiform and other inflammatory skin disorders. PMID- 7792949 TI - Colorized digital transmission electron microscopic images for teaching pathology. AB - We describe how electron microscopic images can be selectively colorized to accentuate ultrastructural detail for teaching purposes. Images are either captured by a CCD camera attached to the electron microscope or are scanned into a computer as electron micrographs. The computer's digital images are then manipulated using image-editing and colorizing software to highlight specific ultrastructural details, and subsequently printed or converted into 35-mm slides to be used for teaching. PMID- 7792950 TI - Case for the panel. "Raspberry" particles in optic nerves from an AIDS patient. PMID- 7792951 TI - Case for the panel. Weibel-Palade body-like lamellar structure in angiosarcoma. PMID- 7792952 TI - Vascular rejection or cyclosporine toxicity? PMID- 7792954 TI - Disseminated toxoplasmosis and acquired immunodeficiency syndrome: diagnosis by transmission electron microscopy. AB - A 43-year-old, bisexual, black man with acquired immunodeficiency syndrome (AIDS), detected by CD4 lymphocyte criteria alone, presented with low-grade fever, chills, malaise, and watery diarrhea of 2 days' duration. Over the next 5 days, he developed a fulminant septicemia-like illness with progressive hypotension, disseminated intravascular coagulation, and very high serum lactic acid dehydrogenase (2,150 U/L) and serum creatine phosphokinase (5,395 U/L) levels, and died. The cause of this illness was not clinically apparent. A bone marrow biopsy performed on the day of his death revealed intracytoplasmic clusters of 3 microns long, oval, basophilic organisms, the exact nature of which was not evident by light microscopy. The diagnosis of disseminated toxoplasmosis (DT) was made only after electron microscopic study of the bone marrow revealed organisms with features typical of Toxoplasma gondii tachyzoites. These features included a multilayered pellicle, a pointed anterior end containing a conoid, up to nine rhoptries, sparse micronemes, and a posterior end containing a nucleus. Some of the organisms had divided by internal budding or endodyogeny. This case illustrates the value of transmission electron microscopy in making the diagnosis of DT. PMID- 7792953 TI - True synovial metaplasia of breast implant capsules: a light and electron microscopic study. AB - The formation of true synovial-lined membranes at tissue sites not intimately related to an articulation or a tendon sheath has been described in a variety of pathologic and postsurgical conditions, but until recently has not been well recognized to occur in association with tissue surrounding silicone breast implants. Of 15 cases with resected periprosthetic breast capsules, 7 (47%) demonstrated true synovial metaplasia with capsule-implant interfaces lined by typical synovial cells. Histochemical and immunohistochemical staining reactions were essentially identical to those observed in synovial control cases and featured positive reactions to Alcian blue-periodic acid-Schiff, reticulin, and vimentin. Focal positive immunoreactivity was observed with alpha 1-antitrypsin, alpha 1-antichromotrypsin, lysozyme, and CD68. No immunoreactivity was observed with cytokeratin AE1/AE3, S-100 protein, carcinoembryonic antigen, or basement membrane antigens. Transmission electron microscopy of the lining cells confirmed their true synovial nature with the type A (macrophage-like) cells, type B (fibroblast-like) cells, and intermediate forms or type AB cells identified. We conclude that the cellular lining surrounding silicone breast implants is a true synovial membrane, that synovial metaplasia may occur in nearly one half of all resected periprosthetic capsules, and that awareness of this entity will enable the surgical pathologist to render an accurate histopathologic diagnosis. PMID- 7792955 TI - [Examination in chronic splanchnic ischemia--arteriography or flow measurement?]. PMID- 7792956 TI - [Intestinal ischemia. Clinical picture and examination methods]. AB - A review of chronic intestinal ischaemia with special emphasis on symptoms, clinical findings, diagnostic procedures and treatment is given. Chronic intestinal ischaemia is not a frequent disease and is often caused by arteriosclerosis. The symptoms are postprandial abdominal pain accompanied by weight loss. The weight loss is mainly caused by reduced food consumption. The diagnosis is traditionally based on angiography and it is recognised that two of the three arteries to the intestines must be affected before the symptoms are experienced. Recently, more functional tests have become available. Especially the measurements of splanchnic blood flow before and after a test meal are used. The lack of a postprandial rise in blood flow is taken as evidence for intestinal ischaemia. Noninvasive methods such as duplex scanning with measurement of portal flow and tonometry seem promising. The treatment is surgical reconstruction of the blood flow or, more recently, percutaneous transluminal angioplasty. The results are generally excellent, although percutaneous transluminal angioplasty in some cases needs to be repeated. The diagnosis and treatment are for a specialist with a special interest. The patients should be concentrated in just a few centres. PMID- 7792958 TI - [Health profile of farmers--a study from Djursland]. AB - The aim of the study was to describe the pattern of illness and the incidence of diseases in a population of Danish full-time farmers. All members of the Farmers Association in Djursland, Jutland, Denmark, (n = 1309), were asked to complete a questionnaire. Of these, 896 (68.4%) accepted, of whom 610 were full-time farmers. The pattern of illness is described by the incidence of chronic disease, the incidence of specific disease, and the incidence of typical symptoms within the last 14 days. Furthermore, the incidence of work-related accidents and the use of medicine were registered. The data were compared with results from a similar investigation in the general Danish population. The incidence of disease in the locomotive and the respiratory system is higher among farmers. In contrast, the incidence of psychiatric and cardiovascular disease as well as insomnia appeared lower. In conclusion full-time farmers have an increased risk of suffering from certain diseases. PMID- 7792959 TI - [The adolescent psychiatric clientele in a district psychiatric center]. AB - This study is retrospective and based on the charts of 44 adolescents (age 17-22) admitted to a Danish community psychiatric centre during the first 32 months after the opening of the centre. The social status of the adolescents, reasons for admission, previous treatment and need for psychiatric treatment are presented. The adolescents were generally a little older than a typical adolescent psychiatric clientele, and comparatively many of them had rather mild psychiatric conditions. A characteristic feature of these patients was a certain instability in their contact to the centre. Although many of them had long lasting basic disabilities (e.g. personality disorders), only a few of them achieved a stable treatment alliance with the ward. This indicates difficulties of integrating an adolescent clientele in a community psychiatric centre that primarily takes care of adult patients. PMID- 7792957 TI - [Percutaneous transluminal angioplasty of iliac occlusions]. AB - Percutaneous transluminal angioplasty (PTA) has become an established treatment modality for iliac artery stenosis. PTA of iliac artery occlusions, however, remains a topic of controversy due to difficulties with mechanical recanalization, a lower patency rate and a higher complication rate than obtained after PTA of iliac artery stenosis. During a three year period, we performed 31 PTA's of iliac artery occlusions. The primary recanalization rate was 71% (22 occlusions). Stents were applied in 16 patients. The cumulated patency rates were 95% and 85% after one and six months respectively. There was one late reocclusion after two years. We found a tendency towards inferior patency in the longer occlusions (> or = 5cm). The complication rate was 10% due to three episodes of distal embolisation, all of which were successfully treated immediately with additional PTA and stenting. These results are in accordance with the results of international studies, and suggest that PTA is a useful alternative to surgical treatment of iliac artery occlusions, albeit long occlusions involving both the common and the external iliac artery should be excluded. PMID- 7792961 TI - [Pressure and flow-profile of different spinal needles]. AB - The flow characteristics of four different types of spinal needles were investigated by measuring the infusion pressure during steady state infusion of either saline or an X-ray contrast agent. Two pencilpoint needles, a Whitacre 22Gauge and a Sprotte 24Gauge, possessed flow characteristics similar to a 22Gauge Quincke point needle. Use of pencilpoint needles for spinal anaesthesia results in a lower incidence of postdural puncture headache compared to the Quincke point needle. We therefore recommended the use of pencilpoint needles for myelography. PMID- 7792960 TI - [Survey of clinical diagnoses and autopsy findings. Autopsy findings and sensitivity, specificity and predictive values for clinical diagnosis during the periods 1 July 1980-30 June 1081 and 1 July 1990-30 June 1993]. AB - The sensitivity, specificity and clinical accuracy of clinical diagnoses were determined and compared for two periods of time: 1.7.1980-30.6.1981 and 1.7.1990 30.6.1993 based on the analysis of 286 and 138 autopsies respectively. The autopsy rate decreased from 82.7% in the first period to 11.2% in the second. The first period shows a generally higher sensitivity and accuracy for positive diagnosis. Both periods reveal the lowest sensitivity for pulmonary embolism and the lowest accuracy for positive clinical diagnosis of pneumonia/bronchopneumonia. For malignancies and arteriosclerotic heart diseases significant discrepancy between the periods was demonstrated using the chi 2 test. The results are influenced by low autopsy rates causing fewer true-positive diagnoses and a declining sensitivity. This type of study is a useful tool for demonstrating changes in the diagnostic procedure. The present investigation demonstrates a need for further analysis of malignancies to explain the simultaneous decrease in sensitivity, specificity and accuracy in spite of an increasing number of malignancies in autopsy findings. PMID- 7792962 TI - [Spontaneous avulsion of the tibial tuberosity following Osgood-Schlatter disease]. AB - Two cases of spontaneous fracture and dislocation of the tibial tuberosity in boys (15 and 19 years of age), who had both suffered from Osgood-Schlatter disease are described. The treatment and prognosis are discussed. PMID- 7792963 TI - [Testicular cancer presenting as acute scrotum]. AB - Acute scrotum is a condition which often causes diagnostic difficulties despite all the available investigation methods. Ruling out or confirming torsion of the testis is the main problem in most cases. Other more rare conditions, however, need acute exploration such as illustrated in this case report, where the sudden bleeding in a testicular neoplasm caused severe acute symptoms. The tumor may not necessarily be clearly apparent during surgery. Peroperative analysis of a specimen of testis tissue is therefore recommended in such cases. PMID- 7792965 TI - [Gynecologic examination--up to date?]. PMID- 7792964 TI - [Ethylene glycol poisoning]. AB - Ethylene glycol poisoning is a rare event in Denmark. The diagnosis can only be made as one of exclusion, since serum ethylene glycol measurements are not made in Danish laboratories. A case report of ethylene glycol poisoning is presented here. Diagnostic problems and treatment are described. PMID- 7792966 TI - [Drug consumption among nursing home residents]. PMID- 7792968 TI - [New puritanism or professional controversy?]. PMID- 7792967 TI - [Is the respiratory syncytial virus underestimated as an etiological factor of severe respiratory tract diseases among the elderly?]. PMID- 7792969 TI - [Smoking habits of Danes]. PMID- 7792970 TI - [Smoking habits of Danes 1988-1993. A follow-up of earlier population studies]. AB - The present study is a six year follow-up of earlier published population studies, where about 18,000 subjects in the normal population over fifteen years of age are interviewed annually in omnibus surveys. The study shows a further continuous fall in the percentage of smokers among males (45% in 1993) and during the last years also a smaller decrease among females (39% in 1993). Smokers of tobacco other than cigarettes have stopped smoking to a greater extent than have cigarette smokers. The most pronounced decrease in percentage of smokers has been observed in the youngest age-group (15-19 years), where smoking prevalence has fallen to about 20%, now with a little higher percentage among females than males. The percentage of heavy cigarette-smokers (15 cigarettes or more daily) is still increasing (now 22% in the male population and 16% in the female population, corresponding to about 800,000 in the total population in Denmark). The increase is especially seen in groups with the lowest educational level. The annual surveys are used as guidelines for directing anti-smoking campaigns in the general population. Future campaigns should in Denmark be concentrated on school children and young people, women between 20 and 40 years, and the increasing group of heavy cigarette smokers. Specific smoking cessation programmes will be run in 1995 (STOP '95). PMID- 7792971 TI - [Changes in smoking habits in a Danish population from 1983 to 1988]. AB - Changes in smoking habits are described for 2,986 danes aged 30, 40, 50 and 60 examined in 1983 as part of the MONICA survey and reexamined five years later. In this period the prevalence declined by 8.1% for men and 5.9% for women. Smoking was related to social class, with an increasing proportion of smokers with decreasing social class. In 1988 the social differences had increased for females. The prevalence of cessation was 17.6% for males and 17.2% for females. The highest proportion of cessation was found among 60 year-old males. The average consumption of tobacco in the group of smokers increased over the period, the increment was higher the younger the person. The prevalence of heavy smokers (20 grams or more daily) increased especially in younger persons. The proportion of young heavy smokers was highest in the lowest social class. By logistic regression a low tobacco consumption was the most important factor associated with cessation. In addition, high social class was associated with cessation for women. PMID- 7792972 TI - [Identification of cancer genes. The need for diagnosis and counseling of families with cancer]. PMID- 7792973 TI - [Pulmonary edema after upper airway obstruction]. AB - Post obstructive pulmonary edema (POPE) is a rare, but potentially dangerous condition. We present two patients with post-anaesthetic POPE. The literature is reviewed and aetiology, risk factors, pathogenesis, symptoms, prophylaxis and management are discussed. The condition is often associated with upper airway obstruction related to anaesthesia, but is also related to other causes of upper airway obstruction. Development of pulmonary edema can be delayed for up to 90 minutes. The treatment consists of oxygen therapy by nasal catheter or by mask with continuous positive airway pressure. In severe cases, intubation and mechanical ventilation by respirator with positive end-expiratory pressure is necessary. Further therapy is controversial and without significant effect. With sufficient therapy, almost all patients regain their habitual condition within 24 48 hours and present a normal chest X-ray. PMID- 7792974 TI - [Occurrence of bulimic behavior among a group of Danish medical students]. AB - As part of a prospective survey of Danish medical student's conditions we looked into the question of the frequency of bulimic behaviour in this group of students. One hundred and ninety-one (75.2%) of 254 students matriculated during 1992-1993 answered a minor structured questionnaire in 1994 about their eating habits, weight and weight control and perception of their bodies. Body mass index was calculated. Forty-five percent of the women and 15.2% of the men admitted to binge-eating, 28.0% of the women and 9.1% of the men admitted to binge-eating together with some kind of weight regulation. Fifty-six percent of the women and 25.8% of the men used some weight regulating procedures, most often exercising and eating less of sweet and fattening foods. Only a very few admitted to self induced vomiting. Binge eating was clearly related to suppressing depressive and negative feelings. Almost 30% of the women were underweight (BMI < 20) but felt themselves to be a normal weight. The male students seemed to be more satisfied with their body and psyche than the women who more often felt overweight and were prone to binge-eating when they felt depressed, and consequently had to regulate their weight in order to live up to their ideals. In order to elucidate the magnitude of the problem of bulimic behaviour and the consequences, we need further surveys of other groups in the Danish population. PMID- 7792975 TI - [Surgical versus non-surgical treatment of unilateral dislocated fractures of the lower mandibular condyle]. AB - To compare open versus closed reduction of unilaterally dislocated low subcondylar fractures in adults, 101 consecutive patients were treated either by closed reduction with a median of four weeks of maxillomandibular fixation or by a median of six weeks of maxillomandibular fixation after surgical repositioning and transosseous wiring of the dislocated condylar fragment. No selection of patients was done for either treatment. Fifty-two patients were observed for a median of two years after treatment. Complications such as malocclusion, mandibular asymmetry, impaired masticatory function, and pain located to the affected joint or masticatory muscles were significantly more frequent in patients treated with closed reduction (39%) compared with those treated surgically (4%)(p = 0.005). Neither the degree of dislocation of the proximal fragment, concomitant mandibular fractures, nor the absence of posterior occlusal support seemed to influence the results. PMID- 7792977 TI - [Ketamine in the management of intractable phantom pain]. AB - A case of phantom limb pain, which had not successfully responded to a long list of medical therapy or neurosurgery, is presented. After oral ketamine treatment was instituted the patient became free of pain. A possible mode of action is described. PMID- 7792976 TI - [Irritable colon among 30-60-year old subjects. A cohort study of 4581 Danes]. AB - With the aim to assess prevalence, incidence, recovery and risk factors of irritable bowel syndrome a follow-up study of 4581 Danes was carried out. The cohort was obtained by a sex- and age-stratified random sample of Danes living in the Western part of Copenhagen County. Participants were interviewed about abdominal symptoms. According to various definitions, the prevalence of irritable bowel syndrome varied from 5 to 65% and the incidence varied from 1 to 36%. At the five year follow-up only 5% of subjects with irritable bowel syndrome were free of all symptoms. Psychic vulnerability, female sex, younger age and having problems were strongly associated to irritable bowel syndrome, while lifestyle factor were not important risk factors. Populations defined as suffering from irritable bowel syndrome according to various definitions had less than 50% of subjects in common. It is concluded that irritable bowel symptoms are frequent, fluctuating phenomena in the general population. Women, the young, the psychic vulnerable, and people having problems are at greater risk of having irritable bowel syndrome. Different studies applying different definitions of irritable bowel syndrome can not be considered to be comparable. PMID- 7792978 TI - [Hemorrhage in cerebral cavernous hemangioma as a cause of hemiballismus]. AB - A 19 year old righthanded woman, without previous neurological symptoms, was examined in April 1993, because of involuntary movements affecting especially the right hand, but also her right leg and the right side of her face. Magnetic Resonance Imagning (MRI), showed a process located in the area of the left subthalamic nucleus, which was recognized as a cavernous haemangioma. A left carotic arteriography in August was normal. The patient had a complete regression of her symptoms, wherefore there was no indication for neurosurgical intervention. The patient is still being followed without treatment. PMID- 7792979 TI - [Hypoxemia and arrhythmia in acute myocardial infarction]. PMID- 7792980 TI - [Anaerobic infection]. PMID- 7792981 TI - [Blood fibronectin and liver phagocytic function in peritonitis patients]. AB - The concentration of blood fibronectin and the state of the phagocytic function in the liver was studied in 19 patients with an emergency pathology of the abdominal cavity complicated by the infective-toxin shock and polyorganic insufficiency. Patients with severe abdominal pathology had a considerably decreased level of circulating fibronectin, disturbed phagocytic function of the liver and development of the hypercatabolic state. Hypofibronectinemia was accompanied by polyorganic disorders, systemic bacteriotoxemia and disseminated intravascular coagulation. Causes of hypofibronectinemia and its role in pathogenesis of systemic complications in patients with emergency abdominal pathology are discussed. PMID- 7792982 TI - [The efficacy of subtotal distal gastric resection in a modified Billroth-I in cancer]. AB - For the period from 1982 to 1994 subtotal resection of the stomach (96) or gastrectomy (10) was performed on 106 patients by the Bilroth-I method. Efficiency of this method is confirmed by the 5 year survival data, which was determined by dynamic method in 42 patients and was 69.8%. Total postoperative lethality was 6.7%, and gastrectomy-4.2%. PMID- 7792983 TI - [The treatment of combined burn lesions of the esophagus and stomach]. AB - In patients with an associated burn injury of the esophagus and the stomach, of determining significance is stenosis of the latter. Resection of the stomach is indicated in cases of subcompensated stenosis of the stomach with distinct boundaries of the scary damage. In parallel with the operation on the stomach for its stenosis, the formation of a gastrostoma of the proximal part of the organ should be also planned for the following bougienage of the esophagus by the directing thread. PMID- 7792984 TI - [Single-stage esophagoplasty for combined chemical burn of the esophagus and stomach and a giant stomach ulcer]. PMID- 7792985 TI - [Malignant villous neoplasms of the large intestine]. AB - An investigation of 532 villous tumors of the colon resected in 490 patients has shown that malignant tumors take place more often in patients with an increased volume of the villous component and the size of the tumor, in patients with more distal localization of adenoma in the colon and in adult people. In 38% of the patients the villous formation was removed through the endoscope, 12% of the patients were subjected to transanal dissection of the rectum tumor and 47.8%--to different operations with resection of the intestine. PMID- 7792986 TI - [Control over the function of the anastomosed segments of the digestive tract]. AB - One of the most effective methods of prophylactics of incompetence of anastomoses sutures is the intraoperative registration of bioelectrical activity of the connected segments of the digestive tract when performing operations on the stomach and esophagus. The implanted electrodes allow analysis of the action potential fluctuation during the postoperative period followed by the corresponding conclusions about the state of blood circulation in hollow organs. The effectiveness and adequacy of management of the patients after the interventions is estimated by means of rheography of the intestine wall. The proposed program of controlling the state of proximal segments of the digestive tract gave good results in 42 patients after total and partial gastrectomies. PMID- 7792987 TI - [Combined strangulated hernia and rectosigmoid phlegmon]. PMID- 7792988 TI - [The pathogenesis of suppurative complications in acute pancreatitis]. PMID- 7792989 TI - [The differential diagnostic difficulties in acute stomach dilatation combined with acute destructive pancreatitis in a patient with a left-sided pneumonectomy in his anamnesis]. PMID- 7792990 TI - [Liver hemangiomas]. PMID- 7792991 TI - [The surgical treatment of lung cancer patients with an exacerbated hereditary factor]. AB - Surgical treatment of 258 patients (1st group) with carcinoma of the lung whose hereditary case history was aggravated by the presence of malignant tumors in blood relatives was compared with treatment of 861 patients of the control group (2nd group). Lung cancer patients of the 1st group were less operable than those of the 2nd group, 60.0% and 71.2% (p < 0.001) correspondingly. Resectability was 84.1% and 93.7% (p < 0.001) correspondingly. Totally in early stages (I-II stages) operations were performed only on 118 patients (45.7%) with the aggravated heredity and 536 (62.2%) of patients of the control group (p < 0.001). The symptoms which characterize surgical treatment of lung cancer in patients with the aggravated heredity are much worse as compared with the control group of patients because of the biological features of the tumors characterized by extremely high potential of the regional and remote metastases. PMID- 7792992 TI - [The therapeutic procedure in different degrees of leakage in the injured lung]. AB - Based of an experience with treatment of 118 patients with spontaneous and posttraumatic pneumothorax, pyopneumothorax and state after resection of the lung, the authors have developed a method of determination of the degree of nonhermeticity of the lung in different regimens of respiration and of the selection of treatment depending on the nonhermeticity of the lung. PMID- 7792993 TI - [Neurological complications after surgical interventions on the branches of the aortic arch]. PMID- 7792994 TI - [Ways to enhance the efficacy of treating patients with the terminal stage of arterial ischemia of the lower extremities]. AB - Experience with treatment of 410 patients with obliterating diseases of lower extremities arteries with the terminal stage of ischemia and occlusions of the femoro-popliteal segment have shown that successful results of small amputations can be obtained but against the background of complex treatment based on a thorough and comprehensive examination of the patient, and aimed at the recovery of adequate blood supply of distal parts of the extremity by operations of direct and indirect revascularization, normalization of microcirculation and struggle against infection. It allows performing amputation distal to the knee joint in 79.5% of cases, and to reduce the amount of postoperative complications in 38.8% of cases. PMID- 7792995 TI - [The immunogenetic status of patients with infectious endocarditis]. AB - On the basis of a deep clinico-immunological examination of 23 patients with septic endocarditis it was established that HLA B35 antigen and haplotype A2-B35 are the most probable markers of the genetic predisposition to the development of infective endocarditis. Immune deficiency is accompanied by a decreased content of T-helpers, decreased activity of natural killers and phagocytic activity of granulocytes. A combination of a genetically determined defect of the immune response with a modification of histocompatibility antigens by infective agents, drugs (narcotics, antigens etc.) and other factors are thought to be of pathogenetic significance in the development of infective endocarditis. PMID- 7792996 TI - [Cellular immune reactions in the victims of explosive injuries to the skull and brain]. AB - Specific features in the immunological status of 49 wounded with explosion injuries of neurosurgical profile are as follows: in light injuries--it is hyperergic character of the immune system and its inadequacy to the injuries of a middle degree it is a distinct parallelism between the dynamics of the immune status indices and the functional state of the CNS depending on the severity of the injury-an extremely flabby with the inhibiting of main immunological indices at a low but permanent level. PMID- 7792997 TI - [Gunshot trauma]. PMID- 7792998 TI - [The clinical aspects of toxic-septic shock in peritonitis]. AB - An analysis of observations of 747 patients with peritonitis is presented, 94 of them had toxico-septic shock. A classification of severity of the shock is proposed in the article as well as principles of making diagnosis and treatment at different steps of management of such patients. PMID- 7792999 TI - [The diagnosis and surgical procedure in wounds of the heart and pericardium]. PMID- 7793001 TI - [The computerized functional monitoring of victims with severe mechanical trauma]. PMID- 7793002 TI - [Birth trauma to the central nervous system in premature infants, its incidence and structure]. AB - The analysis of 1097 newborns case reports is carried out, the high frequency (86.4%) of congenital CNS disorders and high diagnostic possibilities of lumbar puncture are showed as well as REG and roentgenography of the vertebral column cervical portion in CNS birth injury diagnostics, which has been revealed in 71.9% of patients (60.8%--trauma of the cervical portion of the vertebral column with haematoma in CNS and 4.8%--haematoma in CNS). Decreasing of vertebral column birth injury frequency and increasing of haematoma cases frequency with enhancing of immature newborns rate are revealed, which ratio in mature and immature of the I, II, III and the IV degrees is as 9.4; 10.6; 5.2; 2.1; 0.6. PMID- 7793000 TI - [Surgical treatment in stab and cut wounds of the neck with esophageal injury]. AB - The author describes methods of surgical treatment of people wounded in the neck area with injuries of the esophagus. Clinical observations are presented which show that breach of the rules of revision of the wound canal and organs of the neck will inevitably lead to a diagnostic error. The method and volume of the surgical intervention for wounds of the esophagus depend on the kind of the injury and time from the moment of trauma. PMID- 7793003 TI - [The experience of 15 years of development in the rehabilitative trend in the surgery of heart defects]. PMID- 7793004 TI - [The use of the hemostatic preparation Kaprofer in emergency surgery]. PMID- 7793005 TI - [A method for closure of the duodenal stump in reconstructive gastric resection after prior vagotomy with a drainage operation]. AB - A new method of duodenal closure in stomach reconstructive resection in patients with pathologic disturbances after vagotomy with drainage operation is worked up. 6 patients have been operated. No postoperative complications were observed. All the method advantages are evident. PMID- 7793006 TI - [The use of the Cell-Saver method of blood preservation in reconstructions of aortic aneurysms]. PMID- 7793007 TI - The effects of feeding emissions from a metal-producing plant upon the immune system of sheep. AB - The aim of our study was to asses the effects of feeding emissions of a plant producing metals from heavy metal-containing ore upon the humoral immunity in sheep. Three-year-old sheep of the Wallachian breed were included in an experiment and they were divided into two groups. The experimental group (5 animals) was administered emission-containing (prevailingly Cu and Zn) capsules for 3 weeks at a dose amounting to the twofold and during week four the threefold of the daily intake of sheep bred in the exposed area. The animals were subcutaneously immunized with ovalbumin (OVA, SIGMA A 5503) in 10% alhydrogel at a dose of 2 mg/100 kg l.w. In weekly intervals, blood samples were analyzed for specific antibody and total immunoglobulin levels. In both groups, OVA antibody formation was most pronounced in the 3rd and 5th weeks of observation. It was significantly (P < 0.01) higher in the experimental animals than in the controls (1.021, 0.641 and 1.138 vs. 0.435, 0.265 and 0.673 in the 3rd, 4th and 5th weeks, respectively). In the experimental group, total immunoglobulin concentrations slightly increased from 33.5 U ZST (starting value) to 38.72 U ZST (final value). As to the total immunoglobulin levels, no significant differences were determined between the two groups. It can be seen from the results that short-term administration of emissions promotes increased specific OVA antibody formation and a slight increase in total immunoglobulin levels. At the same time the ELISA method was proved to be suitable for specific antibody detection as a part of humoral immunity assessment. PMID- 7793008 TI - [Morphologic characteristics of the testes in breeding rams after experimental loading with industrial emissions containing copper]. AB - The aim of this work was to experimentally evaluate the effect of feeding industrial emissions from a copper-producing plant upon Cu accumulation in the testes of six Merino breeding rams. In the experimental animals (4) the daily copper intake from the exhalations was 15 mg/kg l.w. Administration was continued until the haemolytic crisis appeared (on day 42 in one animal and on day 50 of the experiment in the other animals). The tissue of the testes was examined by both optic and electron microscopy. The patho-anatomical picture of the organs was characterized by general icterus which was also evident on the sectional surfaces of the testes. In the right and left testis of the experimental animals Cu levels were found that were twice higher than those of the controls (Tab. IV). The toxic effect of copper became evident by the destruction of all developmental stages of germinative cells mainly by that the integrity of the cell membranes was damaged thus resulting in a gradual release of the germinative cells, into the tubular lumen. In extreme cases the tubules were lined with nuclei only and the residual cytoplasm of Sertoli cells (Sertoli cells--only syndrome). Ruptures of the cytoplasmic membranes were also observed on the Leydig cells. Thickening of the tubular lamina propria was caused by homogenization and enormous invagination of the lamellar layer, which was rather predominant on the periphery of the organ (Fig. 2). In the deeper layers of the testes reduction of the cellular and non-cellular layers of the tubular walls occurred which frequently resulted in the rupture of the basement membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793009 TI - [Pathogenesis of avian mycobacteriosis in the domestic goose (Anser anser f. domestica) and duck (Anas platyrhynchos f. domestica)]. AB - Experimental infections enabled to test susceptibility of the goose and duck to M. avium. After intramuscular implantation of M. avium suspension, local lesions were observed at the spot of puncture in the geese, and miliary tuberculosis of spleen in 35 days, as well as miliary tuberculosis of liver after 69 days. In the ducks, local lesions were found at the spot of puncture in 35 days and miliary tuberculosis of liver and spleen in 69 days. Cultivation demonstrated mycobacteria in various tissues and organs since day 12 after infection. Peroral infection with contaminated feed caused lesions in spleen and intestine in the geese in 106 days, and then in liver and lungs in 133 days. The ducks had lesions in the intestine in 106 days, and in liver and spleen in 133 and 136 days, resp. Cultivation proved sporadic mycobacteria in liver, spleen, lungs and/or bone marrow and brain in both species. No tuberculous lesions were observed in the geese or ducks within 253 days of the experiment after infections by contacts with the TBC fowl. Cultivation demonstrated sporadic mycobacteria in liver, spleen, kidneys, lungs and bone marrow. The goose and the duck are very resistant to M. avium infection. The duck seems to be less susceptible than the duck. PMID- 7793010 TI - [Pathogenesis of avian mycobacteriosis in the domestic turkey (Meleagris gallopavo f. domestica) and guinea fowl (Numida meleagris f. domestica)]. AB - Experimental infections enabled to study susceptibility to M. avium and disease pathogenesis in the turkey and guinea fowl. After intramuscular implantation of M. avium suspension macroscopic tuberculous lesions were observed at the spot of puncture in turkeys in 35 days, and miliary tuberculosis of liver and spleen in 55 days. Cultivation demonstrated mycobacteria in various organs and tissues since day 12 after infection. The guinea fowl showed macroscopic lesions at the spot of puncture in 28 days, and miliary tuberculosis of liver and spleen in 42 days. Cultivation of most tissues gave positive results since day 14 with prevailing massive growth of mycobacteria. After infection with feed contaminated with the liver of the tuberculous fowl isolated tuberculous lesions in liver, spleen and lungs were observed in the turkey in 133 days, and in the intestine in 163 days. Cultivation was successful enough to demonstrate sporadic mycobacteria in spleen and lungs in 106 days. The guinea fowl showed isolated tuberculous lesions in liver, spleen and intestines in 160 days. Cultivation after 160 days also gave positive results, particularly the presence of mycobacteria in liver, spleen and lungs was proved to be massive. After contacts with the tuberculous fowl, the turkeys showed isolated tuberculous lesions in the liver, spleen and lungs since day 218. Cultivation gave positive results since day 218. Isolated tuberculous lesions in liver were observed in the guinea fowl in 180 days, as well as in spleen, lungs and intestines in 270 days. Cultivation demonstrated smaller numbers of mycobacteria in the infected tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793011 TI - [Detection of sarcocystosis in slaughterhouse animals during a veterinary inspection]. AB - The objective of our study was to acquire objective data on the finds of sarcocystiosis incidence in particular species of farm animals during veterinary inspection and to compare the efficiency of different direct diagnostic methods: compression and digestion methods. The examined and observed animals involved sheep, cattle, pigs and goats slaughtered in the packing plants at Ruzomberok, Rimavska Sobota, Trstena, Sabinov and Kosice. The animals were subjected to regular veterinary inspection including aspection focused on predilection spots of sarcocyst incidence. Sarcocysts were investigated in detail in 353 head of sheep, 27 goats, 350 head of cattle and 1,409 pigs. The examination consisted in inspection of the whole body, of cross-sections of muscles and organs. The rate of sarcocyst invasion in meat as well as the size of cysts were largely variable. The highest incidence in sheep was observed on the inner surface of ventral muscles in the region of diaphragmatic ribs (21.4%) and in the region of intercostal muscles (39.6%). The rate of sarcocyst invasion in the organs was highest in the gullet with cysts of various forms and size (in 47% of sheep). Veterinary inspection of the total number of 27 goats revealed at aspection the presence of macrocysts in eight goats, which makes 29.62%, and in six head of cattle (1.7%) and in 13 pigs (0.9%). Regular finds of sarcocysts on a slaughter line were confronted with direct diagnostic methods: compression and digestion methods (Fig. 1, Tabs. I, II and III). Direct diagnostic method confirmed different results, while only the digestion method--trypsin digestion of muscle- can be considered as diagnostically reliable. PMID- 7793014 TI - Prevalence of antibodies to Toxoplasma gondii in army dogs in the Czech Republic and Slovak Republic. AB - Army dogs, mostly German Sheep-dogs, were tested for antibodies to T. gondii using Sabin-Feldman dye test (DT) and complement fixation test (CFT). Titers greater than or equal to 4 and 10 were considered as positive in DT and CFT, respectively. Seroprevalences in the group of 720 dogs from the civil sector of different areas in the former Czechoslovakia were 39.3% and 15.4% in DT and CFT, respectively. During dogs' stay in army seroprevalences decreased only slowly. The decrease was probably due to less possibility to contact sources of infection -dogs were fed with cooked food, kept in pens with a high level of hygiene, and cats were very rare there. Nevertheless, some dogs in the army training centre were infected by T. gondii in that way of dog rearing. PMID- 7793013 TI - [Antibodies to certain infections on large goat farms in the Czech Republic]. AB - On five newly established large goat farms the incidence of antibodies to some chronic and latent infections (arthritis and encephalitis, Q-fever, caseous lymphadenitis and toxoplazmosis) was investigated in the first six months of the year 1994. Agar-gel immunodiffusion did not reveal any antibodies to arthritis and encephalitis of goats (CAE). Complement fixation test did not demonstrate any antibodies to Q-fever. Neither agar-gel immunodiffusion nor neutralization test confirmed any antibodies to caseous lymphadentitis. Complement fixation test (titer 1:8 and more) revealed antibodies to toxoplazmosis at 20.2% of the cases. No clinical symptoms of toxoplazmosis were observed on the investigated goat farms. It was recommended to take a preventive serological examination of goats against CAE, Q-fever and caseous lymphadenitis before they were housed on the given farms. By maintaining high zoohygienic parameters on the large goat farms it is possible to except a decrease in prevalence of antibodies to toxoplazmosis. PMID- 7793012 TI - [The effect of virginiamycin on rumen fermentation in vitro after adaptation of donors to the inoculum]. AB - Virginiamycin is an antibiotic active against grampositive bacteria in the alimentary tract, which is also suitable for supplementation of diets of growing and finishing ruminants. The aim of this work was to specify the effect of virginiamycin on some parameters of rumen fermentation in vitro with inoculi taken from wethers adapted or non-adapted to the virginiamycin intake. Incubations were performed anaerobically at 39 degrees C in serum bottles closed with Bunsen valves. Virginiamycin was added at 0 or 10 mg/l to the rumen fluid diluted with McDougall buffer. Virginiamycin significantly decreased production and utilization of lactic acid, production of methane and decomposition of casein when rumen fluid was taken from non-adapted wethers. Most of its effects disappeared when rumen fluid was sampled from wethers adapted to the virginiamycin intake (100 mg per head daily for 2 months). Adaptation of wethers to virginiamycin was further confirmed by analyses of the rumen fluid which was used for inoculation of in vitro cultures. Molar percentages of acetate, propionate, butyrate and valerate were the same before and after the adaptation. Therefore it can be concluded that the effects of virginiamycin on rumen parameters are not stable and its addition to ruminant diets cannot be recommended, with exception of the milk nutrition period. In the last experiment the stability of virginiamycin in the rumen fluid of adapted wethers was investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793015 TI - [Comparison of the detection of Giardia intestinalis cysts with the presence of specific antibodies in dogs and cats]. AB - We investigated giardiosis of dogs and cats with a view to cysts in fecal samples and antibodies in the blood serum. Cysts were found in 25 fecal samples (5.5%) out of 458. Cysts were excreted frequently in puppies and adolescent dogs. In 15 cases giardiosis was diagnosed together with canine distemper or parvovirosis as an opportunic infection. Indirect immunofluorescence was used for detection of specific antibodies. We tested sera of 588 dogs and specific antibodies were detected in 156 cases (36.5%) in titres 10-160. In basic dilution 1:10 antibodies were detected in 61% positive samples. Titres 20-160 were found in 39% of the positive sera. In cats cysts were found only in 1 fecal sample out of 135 due to the difficulties in obtaining fecal samples for repeated examinations. Specific antibodies were detected in 107 cats (56.9%) out of 188 at titres 10-320. In basic dilution 1-10 antibodies were detected only in 30% of the positive sera but on the other hand in 70% we detected higher titres, i.e. 20-320. We did not consider titre 10 as significantly positive in both dogs and cats because cross parasitic infections frequently occur. The number of serological positive dogs and cats grew with their age because they acquired giardiosis in the course of their life mostly as asymptomatic infection. The detection of specific antibodies cannot be used for the diagnosis because their level in blood serum persists for months. We must tread every dog and cat excreting cysts in fecal samples to stop transmission to other animals and humans-zoonosis. PMID- 7793016 TI - [The effect of high gravity on embryonic development in birds]. AB - An experiment was conducted on Japanese quail and hen hatching eggs that had been incubated, and the embryos were subjected to hypergravitation of 10 G for 10 min on days 1 to 9 of embryonic development. Both the experimental group and the control contained each 20 hatching eggs every day of the experiment (360 eggs in total). A centrifuge of the diameter 1,300 mm was used to create overload (hypergravitation) at the speed of 118 rotations per min. Tab. I shows the layout of the experiment. Embryonic mortality in Japanese quail was investigated during incubation by egg candling on days 1 to 8 and 9 to 14 while suffocated embryos were investigated on days 15 to 17. As for chicks, embryonic mortality was determined by egg candling on days 1 to 8 and 9 to 18, suffocated embryos were determined on days 19 to 21. After incubation was terminated, hatchability in per cent of the fertilized eggs was determined. The results were processed in two stages of development: the first stage days 1 to 5, the second stage days 6 to 9. As can be seen in Fig. 1, hypergravitation did not influence the hatchability of quail eggs in the first stage. But this experimental treatment resulted in a steep fall of hatchability in the second stage of observation in comparison with the control group (the difference is significant P < 0.01). Fig. 2 shows hatchability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793017 TI - [The NEFERM-Test for identification of psychrotrophic bacteria in food]. AB - Identification of gramnegative nonfermentative bacteria by traditional methods requires much labor and time consumption. Therefore in this study we tested the use of an available commercial diagnostic kit and processing of its results by computerized numerical identification systems. Identification involved 83 gramnegative, psychotrophic, nonfermentative, oxidase-positive bacteria isolated from just slaughtered and deep-frozen chickens. The strains were isolated from primary cultures in Psedomonas F and Endo agar, Violet Red Bile agar (IMUNA, OXOID) and King B agar (King et al., 1954), under two cultivation regimes (room temperature for three days and 7 degrees C for 10 days). A commercial kit for diagnostics of nonfermentative bacteria in clinical microbiology under the name NEFERM-test (Lachema a.s., Brno) containing 12 biochemical assays was used for strain identification: GLU, AGR, IND, ESL, SCI, PHS, URE, MAN, XYL, MLT, LAC, NIT. All these assays were conducted parallelly by traditional methods. Additional tests involved the use of OXI and ONPG commercial strips (Lachema a.s., Brno), gelatin and Tween 80 hydrolysis (Pacova and Kocur, 1984) and fluorescein production (King et al., 1954). These identification systems were used to process the results of tests; index and differentiation table (Lachema a.s., Brno) and numerical computerized systems TNW (Czech Collection (Z. Svoboda, Jihlava). Various shortened procedures, identification keys and systems are used to speed up identification of gramnegative nonfermentative bacteria. Available commercial identification kits (API NE20) in form of microassay have been developed particularly for diagnostics of bacteria from clinica materials, which applies to NEFERM-test of the Czech make.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793018 TI - Devitalization of bacterial and parasitic germs in sewage sludge during aerobic digestion under laboratory conditions. AB - The survival of 8 bacterial species (Pseudomonas sp., Salmonella sp., Enterobacteriae, Streptococcus sp., Escherichia coli) was detected in municipal sewage sludge up to 37 hours of mesophilic aerobic digestion under laboratory conditions. The model strain Enterococcus faecium CCM 4231 survived almost twice as long as the above-mentioned isolates. Similar findings, regarding the viability of the microorganisms studied, were also determined during thermophilic aerobic digestion of municipal sewage sludges. The final reduction in the total count of bacteria was not directly dependent on the temperature during aerobic digestion. It may be supposed that E. faecium CCM 4231 strain as a bacteriocin producing strain with a broad antimicrobial spectrum, inoculated into the sludges, could inhibit the growth of microorganisms in the sludges by the way of its bacteriocin activity. Studying the effect of aerobic digestion on the viability of helminth eggs, the observed negative effect of higher temperatures was more expressive in comparison with bacterial strains. During thermophilic digestion process all helminth eggs (Ascaris suum, Toxocara canis) were devitalized. All eggs of T. canis were killed in experiments under mesophilic temperature. However, 32% of nonembryonated A. suum eggs remained viable. PMID- 7793020 TI - An experimental investigation of the costs and benefits of beak trimming in turkeys. AB - An investigation was carried out on 504 BUT 8 female poults to identify the optimum technique and age for beak trimming breeding turkeys, which have to be kept at relatively high light intensities and are thus at serious risk of cannibalism. Different groups of birds were subjected to electronic trimming (Bio beaking) at one day old, cold cutting (with secateurs) at six days or at 21 days, or hot cutting (with a cautery iron) at six days or 21 days old. The behaviour, production traits, feather damage, injuries and mortality of the birds were measured up to 12 weeks old. None of the methods had much effect on the behaviour or production traits, other than relatively minor reductions in beak-related activities such as pecking other birds and preening, and short term depressions of food intake and bodyweight gain, and improvements in food conversion ratio. All the beak-trimming techniques resulted in marked reductions in mortality (controls 8.7 per cent, trimmed 1.6 per cent), in injuries due to cannibalism (controls 68.1/100 birds, trimmed 9.8/100 birds) and in the scores of feather damage caused by pecking (controls 1.05, trimmed 0.29). The adverse effects of beak trimming were minor and short-lived, and were clearly outweighed by the benefits in reducing cannibalism. Of the different methods, trimming with a hot blade is not recommended. Electronic trimming appeared to offer the most benefits and caused little apparent distress, but can be hazardous in unskilled hands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793019 TI - SEAC reports on transmissible spongiform encephalopathies. PMID- 7793021 TI - Surgical correction of left displaced abomasum in cattle. AB - A left displaced abomasum was corrected surgically in 200 adult cattle by a modification of the method described by Dirksen. Manual repositioning of the displaced organ, localisation of the pylorus and fixation of the greater omentum are described in detail. PMID- 7793022 TI - Prevalence of Actinobacillus seminis in the semen of rams in the United Kingdom. AB - A survey was conducted to establish the prevalence of Actinobacillus seminis in ovine semen and the possible importance of the organism as a cause of ram infertility. A seminis was isolated from three of 16 infertile rams and the infected animals had lesions of the genital tract and produced poor quality semen. A seminis was also isolated from two of 96 fertile rams used as donors of semen for artificial insemination programmes. The strains of A seminis could be identified on the basis of their API ZYM profiles. The results suggest that in the United Kingdom A seminis should be considered as a common cause of infertility in rams. PMID- 7793024 TI - Possible effect of microbial infection on yolk utilisation in ostrich chicks. PMID- 7793023 TI - Dual infection with bovine immunodeficiency virus and bovine leukaemia virus in Mississippi dairy cattle. PMID- 7793025 TI - Docking of puppies' tails. PMID- 7793026 TI - New rules on medicines. PMID- 7793028 TI - 'Normal' blood copper levels in horses. PMID- 7793027 TI - Diagnosis of BSE. PMID- 7793029 TI - Dangerous Dogs Act. PMID- 7793030 TI - Suspected carbon, monoxide poisoning in a dog. PMID- 7793031 TI - Severe post-dipping dermatitis. PMID- 7793032 TI - Spontaneous cataract resorption in an ostrich. PMID- 7793033 TI - Parameters of forelimb ground reaction force in 48 normal ponies. AB - Recordings of forelimb ground reaction forces were made from 48 normal ponies moving at the trot, to evaluate the relationships between bodyweight, vertical ground reaction forces, the timing of individual events within the stance phase and the total contact time. There were highly significant correlations between the mean vertical ground reaction forces and bodyweight. The mean vertical ground reaction forces, corrected for bodyweight, were inversely correlated with the total contact time suggesting that higher trotting speeds may be associated with greater vertical ground reaction forces. The ponies' bodyweights were positively correlated with the contact time, implying a reduced stride frequency with increasing size. The ground reaction force events in the mid and late stance phases occurred at consistent fractions of the total stance time. The ground reaction forces and time parameters were highly symmetrical. PMID- 7793035 TI - Suitability of the intact acrosome method for the prediction of fertility in bovine artificial insemination. AB - The average percentages of sperm with intact acrosomes in eight batches of frozen thawed semen from each of 17 bulls were compared with the non-return rates to artificial insemination by these bulls achieved over a period of three years. Despite the fact that the bulls could be categorised into three statistically significantly different groups according to their non-return rates, there was no significant correlation between the percentage of intact acrosomes and the non return rates of the 17 bulls. PMID- 7793036 TI - Euthanasia of day-old chicks with carbon dioxide and argon. AB - The efficacy for the euthanasia of day-old chicks of mixtures of carbon dioxide and air, or carbon dioxide and argon containing 1, 2 or 5 per cent residual oxygen, or argon containing 1 or 2 per cent residual oxygen was tested in three experiments. The time to the onset of unconsciousness of individual chicks, determined from the time to loss of posture, was similar during their exposure to 2 per cent oxygen in argon, 20, 30 or 40 per cent carbon dioxide in argon with 2 per cent residual oxygen, or 90 per cent carbon dioxide in air. The exposure of chicks in batches of 20 to a mixture of 20, 30 or 40 per cent carbon dioxide in argon resulted in the death of all the chicks within two minutes. However, a residual oxygen level of 5 per cent in these mixtures resulted in the survival of some chicks for longer than two minutes. With argon alone the level of residual oxygen was critical; less than 2 per cent was essential to achieve 100 per cent mortality within three minutes, and a rise from 2 to about 3 per cent resulted in up to 20 per cent of the chicks surviving for seven minutes. PMID- 7793034 TI - Effect of an outbreak of sheep scab (Psoroptes ovis infestation) during mid pregnancy on ewe body condition and lamb birthweight. AB - A naturally occurring outbreak of sheep scab in a flock of 202 ewes during mid pregnancy resulted in exudation from the scab lesions and hypoalbuminaemia lasting for two to 10 weeks in the severely affected ewes. The serum albumin concentration at the time of diagnosis and two weeks after treatment with ivermectin was inversely correlated with the severity of the scab lesions (P < 0.001). The loss of body condition score over a period of 48 days after treatment was significantly correlated with the initial severity of the scab lesions (P < 0.001). Despite adequate energy nutrition of the ewes during late pregnancy, the birthweights of lambs born to ewes with severe sheep scab were 10 per cent less than those of lambs born to ewes with mild sheep scab. PMID- 7793037 TI - Immunohistochemical test for rabies: identification of a diagnostically superior monoclonal antibody. PMID- 7793038 TI - Hydropericardium syndrome outbreak in a pigeon flock. PMID- 7793039 TI - Serological monitoring of PRRS transmission: a case study. PMID- 7793041 TI - Docking of puppies' tails. PMID- 7793040 TI - Docking of puppies' tails. PMID- 7793043 TI - New rules on medicines. PMID- 7793045 TI - Ileocaecal anastomosis in a dairy cow. PMID- 7793044 TI - New rules on medicines. PMID- 7793042 TI - Docking of puppies' tails. PMID- 7793046 TI - Hepatic abscess due to fascioliasis. PMID- 7793047 TI - L-forms of staphylococci and streptococci. PMID- 7793048 TI - [Computed tomography in the diagnosis of gastric cancer]. AB - The potentialities of x-ray computer-aided tomography (CAT) in the studies of intraparietal blastomatous infiltration are analyzed as shown by examinations of 134 patients with gastric cancer. The diagnostic efficacies of various modifications of CAT (filling of the stomach with liquid, pneumoscanning of the stomach with or without tubes) are assessed. Good diagnostic potentialities of tubal scanning of the stomach in the assessment of intraparietal tumor infiltration are demonstrated. CAT semeiotics of gastric cancer is presented, characterizing the tumors with predominantly intraparietal dissemination of blastomatous infiltration. The existent projection limitations of axial CAT of individual portions of the stomach and high price of the examination imply that the indications to the use of this method in gastrooncology should be clearly defined. At the same time, scrupulous adherance to methodologic requirements aimed at imaging of intraparietal changes in gastric cancer may help to solve a number of differential diagnostic difficulties, primarily those connected with predominantly submucously growing carcinomas. PMID- 7793050 TI - [Chronic catheterization of the thoracic lymphatic duct in the treatment of liver cirrhosis]. AB - The suggested method of chronic catheterization of the thoracic lymph duct is based on preservation of lymphaticostoma after a course of lymphosorption. The catheter is removed and a repeated course of lymph perfusion carried out, if necessary. It is particularly important for patients with neglected liver cirrhosis. PMID- 7793051 TI - [Radiodiagnosis of intestinal endometriosis]. AB - Twenty-five women aged 24 to 52, suffering from endometriosis of the large and small intestine were examined. The rectum and the rectosigmoid portion were the most frequent sites of involvement. The endoscopic information is absolutely insufficient. The authors distinguish 4 endometriosis forms with different growth forms and degree of the intestinal wall involvement. Each of these forms has a specific x-ray pattern. The condition is to be differentiated from cancer, regional colitis, strictures and pericolitis by x-ray diagnostic methods. PMID- 7793049 TI - [Effect of radiologic contrast chemoembolization on ultrastructural changes of malignant liver neoplasms]. AB - The authors confirm the efficacy of treating primary and metastatic cancer of the liver by selective blocking of vessels in the involved liver part with an oily x ray contrast agent with a citostatic dioxadet. Profound irreversible injury to tumor tissue was observed. Only solitary tumor cells were left slightly injured. Excepting a narrow adjacent area, lesser amount of lipid tissue accumulated in the tumor; hepatocytes were sufficiently well preserved, showing signs of reparation and increased functional activity 1-2 weeks after chemoembolization. PMID- 7793053 TI - [Contemporary methods of the target puncture of the mammary gland]. AB - New accurate methods of puncture of the mammary gland, making use of preliminary layout using roentgenograms, coordination nets, Cytoguide comprter device, and ultrasound-monitored spot biopsy replaced the traditional poorly informative methods. Sonography-monitored puncture is the most informative in cases with both palpated and unpalpated formations shaped as nodules: it permits imaging in 85% of cases. However, in 25-30% of cases unpalpated cancer presents as microcalcinates and cord-like restructuring which cannot be imaged on sonograms. Moreover, unpalpated cancer presenting as a nodule against the background of fatty involution also may be undiscernible on sonograms. In such cases puncture controlled by roentgenography with a computer device and a relevant kit of disposable instruments is advisable, giving accurate information in 61.1% of cases. PMID- 7793052 TI - [Clinical efficacy of abdominal ultrasonography]. AB - Ultrasonic examinations of the abdomen is suspected visceral diseases may result in the detection of the pathology processes that were not suspected before. To determine the frequency of these unexpected findings, the authors have examined 3000 patients for 2 years. A total of 792 pathology processes were detected that were quite unexpected for the physicians who sent the patients for the examination. Liver tumor were detected in 36 cases, 25 of these metastatic ones, gallbladder stones were detected in 82 cases, tumors and cysts of the kidney and other conditions were detected. The authors come to a conclusion, that no matter what the suspected condition is, the specialist in radiodiagnosis should carry out an ultrasonic examination of the total abdomen. PMID- 7793054 TI - [Current achievements and trends in the development of radiodiagnosis of abdominal and retroperitoneal diseases]. PMID- 7793055 TI - [Radiologic assessment of heart transplantation]. AB - Twenty patients were examined before and after orthotopic transplantation of the heart. The significance of x-ray examination of donors to ascertain brain death was demonstrated. The possibility of x-ray examination of recipients is analyzed. X-Ray criteria of prognostically unfavorable signs for cardiologis patients are defined. The x-ray picture before and after transplantation of the heart was studied. Possible complications in the immediate posttransplantation period are analyzed, as are the potentialities of x-ray detection of chronic crisis of transplanted heart rejection. PMID- 7793056 TI - [Evaluation of imaging validity in mammary-coronary shunts]. PMID- 7793058 TI - [Diagnosis of cancer of solitary kidney]. PMID- 7793057 TI - [Gastric pneumatosis caused by aerophagia]. PMID- 7793059 TI - [Academical science in roentgenoradiology]. PMID- 7793060 TI - [On the history of roentgenology at the Moscow District Research and Clinical Institute and in the Moscow District]. PMID- 7793061 TI - The remarkable coding strategy of borna disease virus: a new member of the nonsegmented negative strand RNA viruses. AB - BDV uses a remarkably broad range of mechanisms to direct expression of its 8.9 kb genome. Although much remains to be elucidated, it is clear that BDV genome expression is modulated by the use of multiple strategies, including differential gene transcription, post-transcriptional modification, and translational efficiency. Further insights into the details of this multilevel system will be essential to understanding BDV biology, pathogenesis, and neurotropism. PMID- 7793062 TI - Nucleotide sequence analysis of a 30-kb region of the bovine herpesvirus 1 genome which exhibits a colinear gene arrangement with the UL21 to UL4 genes of herpes simplex virus. AB - We report the nucleotide sequence of the 19-kb HindIII fragment B of bovine herpesvirus 1 (BHV-1) DNA and adjacent parts of the HindIII A and L fragments, which together span a still completely uncharted 30-kb region located between the glycoprotein H gene and the right end of the unique long segment. The analysis revealed 17 complete open reading frames (ORFs) and 2 ORFs that were interrupted by potential splice donor and acceptor sites. All of these ORFs exhibited strong amino acid sequence homology to the gene products of other alphaherpesviruses. The BHV-1 ORFs were arranged colinearly with the prototype sequence of herpes simplex virus 1 in the range of the UL21 to UL4 genes. Colinearity was also observed with the genes of betaherpesviruses and gamma herpesviruses, although not all ORFs exhibited clear sequence homology. The possible functions of the proteins encoded within the sequenced region are assessed and features found are discussed. Unexpected findings include the following: high amino acid sequence conservation among alphaherpesviruses despite large differences in G + C content, ranging from 45% for varicella zoster virus to 72% for BHV-1; high similarity with other UL20 proteins at the predicted structural level in spite of relatively low amino acid homology; and a 2-kb open reading frame overlapping UL19 in the opposite sense and exhibiting high amino acid similarity to the same area of pseudorabies virus. PMID- 7793063 TI - The genome segments of DpRV, a commensal reovirus of the wasp Diadromus pulchellus (Hymenoptera). AB - The complete nucleotide sequences of the five double-stranded RNA genome segments of the Diadromus pulchellus reovirus (DpRV) have been determined. They consist of 985, 1240, 1318, 1652, and 4230 bp. Each segment contains at least one putative open reading frame encoding 33-, 40-, 45-, 49-, and 148-kDa proteins, respectively. The proteins have no significant similarities with sequences in data banks. Analysis of these segments and of two other previously published segments revealed the presence of degenerate consensus inverted repeats at both ends (5'-rCAAUUUUnnACU...AGUAAAAAAAUnrG-3'). The biological, structural, and genomic features of DpRV suggest that this virus is related to members of the Orthoreovirus genus. PMID- 7793064 TI - Antibodies raised in a natural host and monoclonal antibodies recognize similar antigenic features of foot-and-mouth disease virus. AB - Swine polyclonal antibodies directed against a major antigenic site (site A) of foot-and-mouth disease virus (FMDV) of serotype C, and monoclonal antibodies (MAbs) which recognize different epitopes within this site, have been compared with regard to reactivity with a panel of synthetic peptides. The peptides used represent different segments or variant sequences of site A, and their reactivities reflect differences in antigenic specificity. The results indicate a remarkable immunochemical similarity between the site A epitopes defined by murine MAbs and those recognized by antibodies elicited in a natural host of FMDV. This similarity further validates previous conclusions, based on analyses with MAbs, on the relevance of amino acid substitutions at a few critical positions on the intratypic antigenic variation of FMDV in the field. They also give further support to a dual function of the Arg-Gly-Asp motif of the G-H loop in cell attachment and in the recognition by host antibodies, as recently documented with the elucidation of the three-dimensional structure of an antigen antibody complex of FMDV. In addition, the results encourage the use of extended panels of well-characterized MAbs for a precise molecular analysis of the antigenic variation of FMDV, and of other viruses, in the field. PMID- 7793065 TI - Inhibition of pseudorabies virus replication by a chimeric trans-gene product repressing transcription of the immediate-early gene. AB - A chimeric gene encoding a fusion protein consisting of the DNA-binding domain of the immediate-early (IE) protein of pseudorabies virus (PRV) and a tail-truncated Vmw65 of herpes simplex virus 1, lacking the transcription activation domain, was constructed. The chimeric gene product inhibited transcription from the PRV IE promoter in a transient expression assay. A HeLa cell line stably transformed with the chimeric gene showed remarkable resistance to PRV infection. In the transformed cells infected with PRV, transcription of the PRV IE gene was repressed, indicating that the resistance of the cells to PRV infection was due to interference with IE gene transcription by the fusion protein. PMID- 7793068 TI - Studies on neurovirulence in poliovirus-sensitive transgenic mice and cynomolgus monkeys for the different temperature-sensitive viruses derived from the Sabin type 3 virus. AB - We have studied methods for testing the neurovirulence of live poliovaccine viruses by intraspinal inoculation into mice carrying the human poliovirus receptor gene (Tg mice). A comparison of the neurovirulence of Sabin type 3 vaccine virus and related viruses using the 50% paralysis dose determined after intraspinal inoculation into the Tg mice as an index revealed a close correlation between the results of the paralysis dose in Tg mice, the neurovirulence expressed by the histopathological lesions core in monkeys, and the temperature sensitivity of the viruses. The results of experiments in the Tg mice also showed a good correlation with the number of mutations at position 472 from U to C in the 5' noncoding region in the genomes of the viruses tested. These results strongly suggest that the neurovirulence test for oral poliomyelitis vaccine using the Tg mice is an excellent method and may be used in place of the test using monkeys. PMID- 7793067 TI - An arbovirus cline across the northern hemisphere. AB - The mode and tempo of arbovirus evolution and dispersal can help to explain the dynamics of pandemics, viral outbreaks, and emerging viruses. By comparing nucleotide and deduced amino acid sequences of their envelope proteins, we describe the continuous distribution of the tick-borne encephalitis (TBE) complex viruses, the most important flaviviruses in Europe, across major geographical areas and the conditions under which mutations occur. The analyses reveal a correlation between the geographical and genetic distances of these viruses. The arthropod host appears to be a key factor for the formation and maintenance of this cline by constraining TBE dispersal and evolution. This is also illustrated by comparisons with mosquito-borne flaviviruses. PMID- 7793066 TI - The roles of the cAMP-response element and TATA box in expression of the herpes simplex virus type 1 latency-associated transcripts. AB - A quantitative ribonuclease protection assay (RPA) was developed in order to rapidly and accurately measure the levels and timing of latency-associated transcript (LAT) expression in ganglia latently infected with wild-type and mutant herpes simplex virus (HSV). Use of this assay in parallel with measurement of viral titers in murine trigeminal ganglia demonstrated that the peak of viral replication precedes the peak and subsequent plateau of LAT expression. This plateau of LAT expression was unaltered from Day 7 through the end of the experimental period on Day 28, suggesting that LAT does not further accumulate during latency of wild-type virus. RPA analyses of trigeminal ganglia latently infected with HSV-1 mutants containing specific alterations in the LAT TATA box, cyclic AMP-response element (CRE), and both TATA and CRE were performed. Mutation of the upstream TATA box reduced LAT expression to 25% of wild-type or marker rescued virus levels, whereas mutation of the CRE did not significantly affect LAT expression in vivo whether in the presence or absence of the TATA box. These experiments demonstrate a specific requirement for the upstream promoter TATA box for wild-type LAT expression. Further examination of the role of the CRE and the TATA box by transient expression assays suggests that the CRE is important for inducible activity and that its interaction with the TATA box requires stereospecific alignment. PMID- 7793069 TI - Replicating foamy virus-based vectors directing high level expression of foreign genes. AB - Replication-competent retroviral vectors (pFOV-1 to -3 and -7) were constructed on the basis of an infectious human foamy virus molecular clone which has deletions in the U3 region of the long terminal repeat and in the 3' region of the genome, previously identified to be nonessential for virus replication in vitro. The CAT and luciferase indicator genes were expressed as C-terminal fusion proteins to 215 amino acids of the viral Bet protein in the pFOV-1 vector. Introduction of the foot-and-mouth disease 2A protease sequence between the truncated bet coding sequence and the cloning site for the insertion of foreign genes in the pFOV-7 vector resulted in self-cleaving of the recombinant fusion protein. Alternatively, an internal ribosomal binding site was introduced, allowing expression of authentic foreign protein (pFOV-2 and -3 vectors). DNA fragments derived from the mouse hepatitis virus surface gene up to the length of 1.3 kb were inserted into pFOV-1. The vector constructs gave rise to viruses which were fully infectious in diploid human fibroblasts and recombinant viruses stably expressed high levels of foreign protein indicating that the pFOV vectors may be useful tools to study the effects of proteins of interest at least in tissue culture cells. PMID- 7793070 TI - Expression and purification of a recombinant tobacco etch virus NIa proteinase: biochemical analyses of the full-length and a naturally occurring truncated proteinase form. AB - The tobacco etch virus 27-kDa nuclear inclusion a (NIa) proteinase was expressed in Escherichia coli as a recombinant fusion protein containing a seven-histidine tag at the amino-terminus. Catalytically active and inactive (by virtue of a single amino acid change) forms of the proteinase were purified to homogeneity in a two-column chromatographic procedure. The active form of the proteinase was slowly converted to a lower molecular weight form, while the inactive form was not. This conversion was dilution independent and thought to be intramolecular. Isolation of the approximately 2-kDa peptide cleavage product and determination of its N-terminal amino acid sequence positioned the cleavage site 24 amino acids from the carboxy-terminus of the proteinase. A recombinant NIa proteinase lacking the C-terminal 24 amino acids was shown to possess limited activity. Kinetic analyses of cleavage of a synthetic peptide by the full-length or truncated proteinase were conducted and indicated that the Km of the truncated proteinase was approximately fourfold higher than that of the full-length form. The truncated proteinase was approximately one-twentieth as efficient in proteolysis of the test peptide substrate as the full-length form. PMID- 7793071 TI - Assessment of fusogenic properties of influenza virus hemagglutinin deacylated by site-directed mutagenesis and hydroxylamine treatment. AB - Influenza virus hemagglutinin (HA) subtype H7 expressed from a baculovirus vector in insect cells requires cysteine residues for palmitoylation. Mutant HA devoid of fatty acids shows hemagglutinating and hemolytic activities almost identical to those of the acylated wild-type HA (wt). Using a membrane mixing assay (R18), neither the kinetics nor the pH dependence of fusion induced by wt or mutant HA was significantly different from virus-induced fusion. HA-induced fusion of insect cells with human erythrocyte ghosts could also be demonstrated by a cytoplasmic content mixing assay. Both species of recombinant HA induced the flow of lucifer yellow from preloaded ghosts into the cytoplasm of HA-bearing cells. This indicates that membrane fusion mediated by wild-type and fatty-acid-free HA includes both leaflets of the lipid bilayers. Hydroxylamine treatment of wt HA (H7) and fatty-acid-free mutant HA present in lysates of insect cells led to the complete inhibition of hemolytic activity. Deacylation of spike proteins by NH2OH treatment of virus particles resulted in a block of hemolytic activity in influenza virus subtypes H7 and H10 as well as of that in the togaviruses Semliki Forest and Sindbis virus. However, the same treatment did not affect subtypes H2 and H3 or two vesicular stomatitis virus serotypes. With such a differential effect whether or not fatty acids are present in the spike proteins of the different virus particles, hydroxylamine must have other effects than just deacylation, and therefore seems unsuitable for the study of the biological functions of acylproteins. PMID- 7793072 TI - Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. AB - The vaccinia virus/bacteriophage T7 hybrid transient expression system employs a recombinant vaccinia virus that encodes the T7 RNA polymerase gene, a plasmid vector with a gene of interest regulated by a T7 promoter, and any cell line suitable for infection and transfection. Although high expression in a majority of cells is achieved, the severe cytopathic effects of vaccinia virus and the safety precautions required for use of infectious agents are undesirable features of the system. Here, we report the construction of a highly attenuated and avian host-restricted vaccinia virus recombinant that encodes the T7 RNA polymerase gene (MVA/T7 pol) and demonstrate the use of the virus for transient expression in mammalian cells. MVA/T7 pol has reduced cytopathic effects compared to the previously used replication-competent vaccinia virus, while providing a high level of gene expression in multiple mammalian cell lines. PMID- 7793074 TI - Crystallization and preliminary X-ray analysis of the core particle of bluetongue virus. AB - Core particles of bluetongue virus serotype 1 (South Africa) have been crystallized. The crystals, which grow up to 0.8 mm in diameter, belong to a primitive orthorhombic space group and have point group symmetry 222. The unit cell dimensions are 754 x 796 x 823 A3 and the crystallographic asymmetric unit contains one-half of a core particle. The best crystals diffract strongly to 4.8 A Bragg spacings, which is the maximum resolution to which we can measure data with the detectors available, suggesting that useful diffraction extends well beyond this. Core particles of serotype 10 have also been crystallized but the crystals have yet to be analyzed by X-ray diffraction. PMID- 7793073 TI - Impaired infectivity of HIV-1 after a single point mutation in the POL gene to escape the effect of a protease inhibitor in vitro. AB - To examine whether the mutation of protease in an HIV-1 resistant to a protease inhibitor affects the virus phenotype in vitro, the infectivity of the protease inhibitor-escape-virus was compared to that of the parent virus. In different T cell lines, the infectivity of the escape virus was impaired by 10-fold compared to the parent virus. MT-4 cell killing by the escape virus, measured using the MTT assay, was much weaker than that by the parent virus. The escape virus contained more unprocessed Pr55gag than the parent virus. A delayed appearance of mature p24 in cells chronically infected with the escape virus was also noticed by the pulse-chase method. The same findings were obtained using pNL432 (HIV-1 DNA molecular clone) with the same mutation in the protease gene. Despite the lack of a significant difference in virus binding, less unintegrated and integrated DNA was detected in MT-4 cells infected with the escape virus compared to the parent virus. The impaired infectivity of the escape virus may be explained by the inefficient maturation of Gag proteins, due to the mutated protease, which may affect an early step in the virus life cycle. PMID- 7793075 TI - HIV-1 infection of primary human neuroblasts. AB - Central nervous system (CNS) disorders are frequent in HIV-1-infected individuals, particularly in newborns and children, and are accompanied by histological alterations resulting in neuronal loss. Although several tumor derived neuroectodermal cell lines can be infected by HIV-1, it has been reported that primary neural cells cannot be infected after they differentiate. However, pediatric AIDS is often the result of HIV-1 infection occurring during fetal development and early postnatal life, when neural cells are not yet differentiated. Here we show that primary cell cultures derived from the human fetal olfactory system which are representative of the developing CNS can be infected by both HIV-1 strains, the monocyte-macrophagotropic BaL and the lymphotropic HTLV-IIIB, although they do not express the CD4 molecule. In addition, the levels of viral replication are higher with the HIV-1 BaL than with the IIIB isolate. These results suggest that (1) during development immature neurons are susceptible to HIV-1 infection; (2) monocyte-macrophagotropic HIV-1 strains may preferentially be involved in the productive infection of the nervous system; and (3) a mechanism(s) other than the CD4-mediated viral entry is responsible for HIV-1 infection of immature neurons. PMID- 7793076 TI - Foreign gene expression by human adenovirus type 5-based vectors studied using firefly luciferase and bacterial beta-galactosidase genes as reporters. AB - Adenovirus (Ad) vectors have been used extensively to obtain high-level expression of foreign genes in mammalian cells and are currently being studied for use as live viral-vectored vaccines and as gene transfer vectors for gene therapy. Many Ad recombinants have been generated that express foreign genes inserted in early region 3 (E3); however, little has been done to study the importance for gene expression of regulatory sequences flanking the gene. We have generated a series of Ad5 helper-independent vectors that contain the firefly luciferase gene or the bacterial beta-galactosidase gene (LacZ) with or without simian virus 40 (SV40) regulatory sequences, combined with E3 deletions of 1.88 or 2.69 kb. The greatest levels of luciferase expression were obtained with a vector containing the luciferase gene under the control of the SV40 promoter and polyadenylation signal inserted in a 1.88-kb E3 deletion. In contrast, LacZ expression was highest with a vector containing the LacZ gene with just the SV40 polyadenylation sequence combined with a 1.88-kb E3 deletion. It was also observed that regardless of the SV40 sequences flanking the reporter gene or the E3 deletion used, expression from the luciferase recombinants was dependent on viral DNA replication, whereas expression from the LacZ recombinants was only partially reduced when DNA replication was blocked. Analyses of RNA by dot blot hybridizations revealed that the levels of reporter gene-specific mRNA for various vectors in each series did not vary significantly. These results indicate that the kinetics and efficiency of expression of genes inserted into the E3 region, in nonconditional helper-independent vectors, may be more strongly dependent on the sequences in the foreign gene insert itself than on flanking regulatory sequences such as those used here, derived from SV40. PMID- 7793077 TI - Sequence analysis of pigeon, turkey, and chicken rotavirus VP8* identifies rotavirus 993/83, isolated from calf feces, as a pigeon rotavirus. AB - Partial-length gene 4 cDNA encompassing the VP8* portion of VP4 from chicken rotavirus (RV) Ch-1, turkey RV Ty-1 and Ty-3, and pigeon RV PO-13 was sequenced and compared to RV 993/83 isolated from a calf with diarrhea. Ninety-six percent amino acid sequence identity was seen between VP8* from calf RV 993/83 and pigeon RV PO-13, while only 77 to 83% identity was seen in comparison with turkey and chicken RV VP8* sequences. Phylogenetic tree analysis places all avian RV (including calf isolate 993/83) on a branch at the bottom of the VP8* tree. When tested with three neutralizing monoclonal antibodies raised against pigeon RV PO 13, RV 993/83 and Ty-1 share three, Ch-1 shares two, and Ty-3 shares one neutralizing epitope(s) on VP4 with pigeon RV PO-13. PMID- 7793078 TI - CTL escape viral variants. I. Generation and molecular characterization. AB - Cytotoxic T lymphocytes (CTL) play a pivotal role in preventing persistent viral infections and aborting acute infections. H-2Db-restricted CTL optimally recognize a specific peptide of 9 to 11 amino acids (aa) derived from a viral protein and held in place (restricted) by a MHC class I glycoprotein on the surfaces of infected cells. Only three peptide sequences with the appropriate Db motif from lymphocytic choriomeningitis virus Armstrong strain (LCMV) are known to be presented to CTL by H-2Db molecules; they are from the glycoproteins (GP), residues 33-41 KAVYNFATC (GP1) and 276-286 SGVENPGGYCL (GP2), and the nucleoprotein (NP), 396-404 FQPQNGQFI. Incubation of virally infected H-2b cells with CTL clones that recognize only GP1, GP2, or NP leads to the selection of viral variants which upon infecting cells bearing H-2b molecules, escape recognition by CTL of the appropriate specificity. Nucleic acid sequencing showed a single mutation in GP1 (aa 38 F-->L), GP2 (aa 282 G-->D), or NP (aa 403 F-->L) in the variant viruses. When wild-type (wt) LCMV peptides and the three variant peptides (GP1, GP2, NP) were synthesized and subjected to a competitive inhibition binding assay, no differences in binding affinity for H-2Db were found between the wt and variant peptides. Uninfected cells coated with the wt peptide were recognized and lysed by the appropriate CTL clone or by in vivo-primed bulk CTL, but similar targets coated with the GP1, GP2, or NP variant peptides were not. This result, coupled with computer graphic analysis of these variant peptides with the recently solved three-dimensional structure for the Db MHC class I molecule, placed the side chain of the mutated residues on the outer surface of the MHC-peptide complex and accessible to the T cell receptor. Ala substitution at GP residue 38 or 282 or at NP 403 also abrogated CTL recognition and lysis. Inoculation of any one of the mutated viral variants into mice produced an effective CTL response to the other two nonmutated GP or NP peptides, suggesting that production of biologically relevant CTL escape virus variants in vivo requires selection of mutations in more than one and likely all the CTL epitopes, a low probability event. PMID- 7793079 TI - Host effects and sequences essential for accumulation of defective interfering RNAs of cucumber necrosis and tomato bushy stunt tombusviruses. AB - Passage of cucumber necrosis virus (CNV) containing defective interfering (DI) RNAs through cucumber plants decreased the accumulation of DI RNAs to undetectable levels. Subsequent passages in two Nicotiana species (Nicotiana benthamiana or N. clevelandii) resulted in the appearance of DI RNA species that were larger than the DI RNAs observed during exclusive serial passages of CNV through the Nicotiana species. Sequence analysis of cloned cDNAs corresponding to the two DI RNA populations indicated that the smaller CNV-DI RNAs contained the four conserved regions (I through IV) of the genome typical of tombusvirus DI RNAs, whereas the larger DI RNAs were of similar organization but had a direct repeat of the middle portion of the molecule. This result suggests that the host has an influence on the type of DI RNA that accumulates during consecutive high multiplicity of infection passages. A comparative analysis of deletions targeting the individual conserved regions in both CNV and tomato bushy stunt virus (TBSV) DI RNAs revealed that only region III was completely dispensable for accumulation of either DI RNA species. More refined deletion analyses in regions I and II indicated that smaller segments of 75 and 35 nucleotides (nt), respectively, could be deleted without abolishing infectivity. The dispensable sequences in region II of both TBSV and CNV DI RNAs mapped to the top portion of a putative stem-loop structure. These studies indicate that both essential and nonessential sequences are conserved in DI RNAs. The essential sequences in regions I, II, and IV likely contain important cis-acting elements, whereas nonessential regions such as region III may play secondary roles such as optimally spacing cis-acting elements or maintaining the DI RNA at an overall size that is stable. PMID- 7793080 TI - MHV-A59 enters polarized murine epithelial cells through the apical surface but is released basolaterally. AB - Coronaviruses have a marked tropism for epithelial cells. Entry and release of the porcine transmissible gastroenteritis virus (TGEV) is restricted to apical surfaces of polarized epithelial cells, as we have recently shown (J. W. A. Rossen, C. P. J. Bekker, W. F. Voorhout, G. J. A. M. Strous, A. van der Ende, and P. J. M. Rottier, 1994, J. Virol. 68, 7966-7973). In this paper we analyze the interactions of mouse hepatitis coronavirus A59 (MHV-A59) with polarized murine kidney cells (mTAL) grown on permeable supports. After inoculation from the apical or basolateral side, virus entry was found to take place only through the apical membrane. The virus utilized a protein of the carcinoembryonic antigen family as its receptor. In contrast to TGEV, MHV-A59 was released preferentially from the basolateral plasma membrane domain, as evidenced by the accumulation of viral proteins and infectivity in the basolateral culture fluid as well as by electron microscopical observations. In the mouse, MHV initially replicates in the nasal epithelium before being disseminated throughout the body; the basolateral release of MHV from epithelial cells into the animal's circulation may be the first step in the establishment of a systemic infection. PMID- 7793081 TI - Unclassified poxvirus: characterization and physical mapping of Cotia virus DNA and location of a sequence capable of encoding a thymidine kinase. AB - DNA from Cotia virus, an unclassified poxvirus, was mapped by overlapping fragment analysis using the restriction endonucleases HindIII, PstI, BamHI, XhoI, SalI, and SmaI. The linear genome was 177 kbp in length and possessed inverted terminal repeats and cross-links. A Cotia virus thymidine kinase (TK) gene was detected and mapped to about 74 kbp from the left end of the genome using degenerate oligonucleotide probes. Nucleotide sequencing of the TK gene revealed an open reading frame (ORF) that encoded a peptide of 178 amino acids. An A/T rich sequence, TAA AAA TGA ATA AATA, and a transcription termination signal, TTTTTGT, were revealed upstream and just downstream of the ORF, respectively, consistent with the characteristic features of an early poxvirus gene. Cotia virus resembles swinepox virus based on the restriction profiles generated by endonucleases and shares amino acid sequence similarity with orthopox, leporipox, Yaba, and fowlpox viruses. PMID- 7793083 TI - Quantitative analysis of the binding of turnip crinkle virus coat protein to RNA fails to demonstrate binding specificity but reveals a highly cooperative assembly interaction. AB - An element(s) within a 386-nucleotide segment (TCV-386 RNA) of the turnip crinkle virus (TCV) genome was previously implicated in virus assembly nucleation. To localize the proposed high-affinity binding determinants, we analyzed the ability of the coat protein to bind the full-length and truncated derivatives of the TCV 386 RNA using gel retardation and nitrocellulose filter retention assays. Quantitation of the binding data indicated that the coat protein did not preferentially recognize a particular region of the RNA. Moreover, the affinity of the coat protein for the TCV-386 RNA [apparent dissociation constant (Kd) approximately 0.5 microM) did not appreciably differ from its affinity for other comparably sized RNAs tested, including nonviral RNAs. However, the quantitative studies also suggested that the coat protein binds RNA in a cooperative manner and this was supported by evidence that all of the RNAs examined were bound by multiple copies of the coat protein. Based on the number of binding intermediates which could be detected in titrations involving RNAs of different chain length, it appeared that each coat protein binding unit occupies 35-40 nucleotides. Our results demonstrate that encapsidation of TCV RNA results from highly cooperative binding of the coat protein on the large viral genome. However, we were not able to confirm that assembly is mediated by initiation at a high-affinity binding site on the viral RNA. PMID- 7793082 TI - The small cysteine-rich protein P14 of beet necrotic yellow vein virus regulates accumulation of RNA 2 in cis and coat protein in trans. AB - The effect of null mutations of the small cysteine-rich protein P14 encoded by RNA 2 of beet necrotic yellow vein virus has been investigated using in vitro transcripts of viral RNA to infect Chenopodium quinoa protoplasts. The P14 mutations down-regulated RNA 2 accumulation by approximately 10- to 50-fold. Accumulation of minus-strand RNA 2 was also diminished but RNA 1 accumulation was much less affected. The inhibition of RNA 2 accumulation could not be complemented in trans by providing P14 from another source (either a second molecule of RNA 2 or an RNA 3-based replicon) containing and expressing the P14 gene. The P14 null mutations dramatically inhibited accumulation of viral coat protein, which is encoded by the 5'-proximal gene on RNA 2, but this effect could be complemented in trans, indicating that it occurs by a mechanism distinct from that affecting RNA 2 accumulation. Transient expression experiments were also carried out in which a plasmid expressing P14 and plasmids expressing a reporter gene placed downstream of potential translational control sequences (the 5' noncoding sequences of RNAs 2, 3, or 4) were introduced into C. quinoa or Nicotiana tabacum leaves by microprojectile bombardment. Coexpression of P14 produced a 3- to 4-fold stimulation of reporter gene expression levels for all the constructs. The lack of sequence specificity suggests that this phenomenon is not directly related to the RNA 2-specific stimulation of coat protein accumulation observed in a viral infection. PMID- 7793084 TI - Characterization of putative defective interfering (DI) A/WSN RNAs isolated from the lungs of mice protected from an otherwise lethal respiratory infection with influenza virus A/WSN (H1N1): a subset of the inoculum DI RNAs. AB - Defective interfering (DI) influenza virus A/WSN (H1N1) grown in embryonated eggs protected adult mice from a lethal respiratory infection with A/WSN virus. Eighteen bands of putative DI RNA, ranging in size from about 230 to 1020 nt, were identified in this preparation by reverse transcription and polymerase chain reaction using a segment-specific 3' primer and a segment-universal 5' primer. Every virion RNA segment was represented by one to four bands of putative DI RNA. However, only five bands of putative DI RNA could be isolated, using the same conditions, from lungs of WSN-infected mice protected from death by co inoculation with egg-grown DI WSN. These five bands originated from PB1, PB2, PA, and M virion RNAs and were all about 350-450 nt in length. Four putative DI RNAs originating from PB1, PB2, and PA virion RNAs were sequenced, and three were identical (including deletion junctions and base substitutions) to putative DI RNAs from the inoculum. These data suggest that the mouse lung was highly selective for a subset of inoculum DI RNAs and that one or more of these DI RNAs was responsible for protection in vivo. All putative DI RNAs had a single internal deletion. PMID- 7793085 TI - Entry and release of measles virus are polarized in epithelial cells. AB - The initial site of virus replication during measles infection is in the epithelial cells of the respiratory tract. We have investigated measles virus infection of two types of polarized epithelial cells to determine if entry and/or release of the virus is confined to either the apical or the basolateral plasma membrane. The Caco-2 line of human intestinal epithelial cells and the polarized Vero C1008 monkey kidney cell line were grown on permeable supports and inoculated either through the apical or basolateral surfaces. Cells exposed to virus in the apical medium showed high levels of synthesis of virus-specific proteins, whereas no synthesis of viral proteins was detected in cells inoculated at the basolateral surface. Virus titers derived from apically infected cells were found to be about 1000-fold greater than titers derived from cells infected at the basolateral surface. Indirect immunofluorescence results also demonstrated that expression of measles viral antigens occurs at high levels only when input virions are inoculated at the apical surface. To investigate the localization of CD46 and moesin, which are receptors for measles virus, Caco-2 cells were incubated with monoclonal antibodies against CD46 or moesin followed by 125I labeled anti-mouse Ig. The results indicate that CD46 is expressed preferentially on the apical membranes while moesin appears to be present at similar levels on both surfaces. Release of the virus was also examined and found to be polarized as well. Virus was released into the apical medium at up to 1000-fold higher titers than virus released into the basolateral medium. These results demonstrate that in two epithelial cell types measles virus preferentially enters and is released from epithelial cells in a polarized fashion through the apical plasma membrane. PMID- 7793086 TI - [Mechanisms of inhibiting production of tumor necrosis factor alpha by the synthetic hexapeptide--immunophane]. AB - The authors examined the human blood mononuclear-induced tumor necrosis factor production using the new drug--the synthetic hexapeptide Immunophan. The levels of tumor necrosis factor in the supernatant liquid were measured by the enzyme immunoassay and the cytotoxic test using L-929 fibroblastoid cells. Following 2-8 hours of short-term incubation of mononuclear cells with Immunophan, there was a reduction in spontaneous or lipopolysaccharide - or ionophore A23187-induced production of tumor necrosis factor. As high as 5-20% of plastic-nonadherent cells treated with Immunophan in a concentration of 0.25 mu/ml were found to produce the same effect. Two-four hours after Immunophan activation, the cells produced into the supernatant liquid soluble factors with a molecular weight of 70-85 kD that suppressed the production and activity of tumor necrosis factor. Thus, the modulating effect of Immunophan against tumor necrosis factor production is associated with the induction of regulatory cells producing the soluble receptors of tumor necrosis factor. It is suggested that extrabody pharmacological induction of the cells that regulate the production of tumor necrosis factor, followed by their subsequent administration into the autologic organism might be used while developing new variants of extracorporeal treatments of the diseases which are characterized by the pathogenetically significant hyperproduction of the inflammatory cytokins,--tumor necrosis factor, interleukin 1, interleukin-6. PMID- 7793088 TI - [Tissue hypoxia: clinical-biochemical aspects]. PMID- 7793087 TI - [The effect of application-sorption therapy on dynamics of activity of molecular carriers of electrons of the energetic and detoxifying systems of cells in experimental burn disease]. AB - Integral free radical state, paramagnetic enzyme complexes of nonheme iron with sulfur- and nitrogen-containing ligands in mitochondria and heme iron in microsomes as well as metalloenzymes of blood plasma ceruloplasmin and transferrin were studied in dynamics of burn disease in rats. Significant decrease in content of reduced ferrosulfur proteins in mitochondrial energy system was observed in kidneys within the second day after the burns and in liver tissue within the 14-21 days after the failure which correlated with reduction of cytochrome P-450 oxidized form. Development of paramagnetic nitrosyl complexes of heme and nonheme iron, specific for hypoxia, were detected in the impaired muscle tissue. Increase in tissue hypoxia was accompanied by decrease in content of transferrin and by elevation in the antioxidant activity of blood plasma. Application of local adsorption after early excision of burns crust contributed to normalization of both metabolism in the impaired tissues and in activity of the electron transport chain in liver and kidney tissues. Therefore, local adsorption therapy may be considered as an alternative procedure in sorptional detoxication of burns. PMID- 7793089 TI - [Effect of natural complexes of biologically active substances on liver regeneration in alcohol poisoning]. AB - Hepatoprotective effect of natural substances obtained from extracts of grape combs, leaves of green and black tea were studied in liver tissue of ethanol consuming rats by means of evaluation of the neutral lipid fractions and phospholipids as well as by measurement of glucose and nicotinamide coenzymes NAD+ and NADP in blood. In all the animal groups treated with these vegetable extracts content of total phospholipids, decreased after the ethanol treatment, was increased, while fraction composition of phospholipids and of neutral lipids was normalized; in blood content of glucose, NAD+ and NADP approached to control values. These results suggest that the vegetable extracts studied exhibited the hepatoprotective effect in alcohol intoxication. PMID- 7793090 TI - [Erythrocyte lipids and the gas transport function of blood in acute hemorrhage]. AB - Alterations of erythrocyte lipid composition were studied during oxygenation of the cells in rabbit lesser circulation in simultaneous single massive hemorrhage. The state of blood respiratory function was studied in order to evaluate an importance of the erythrocyte membranes transformation occurred in lungs during gas exchange; for this purpose arteriovenous difference in oxygen and coefficient of erythrocyte deoxygenation were evaluated. Increase in content of phosphatidyl serine in erythrocytes during blood arterial transformation was shown to correlate highly with arteriovenous difference in oxygen. Pathophysiological importance of the alterations observed is discussed. PMID- 7793091 TI - [Effectiveness of lignin as a protective factor in exposure to polychlorinated biphenyls]. AB - The effect of lignin on some biochemical and morphological parameters was studied in rats after short-term treatment with the industrial mixture of polychlorinated biphenyls (PCB) sovol at a daily dose of 5 mg/kg, 5 times a week for a fortnight. Dietary supplementation of 5% lignin as the drug polyphenane did not protect the induction of the rat hepatic P-450 cytochrome monooxygenase system, which is typical of the action of PCB, but slightly modified the inducing effect of sovol. In the polyphepane-fed animals, there was a decrease in impairments of the liver structure and its more rapid normalization than in control rats. The lower hepatotoxic effect of the PCB mixture when lignin was added to the ration was likely to be associated with the action of lignin as a nonspecific polyvalent enterosorbent. It is concluded that polyphepane is a promising protective agent on exposure to PCB. PMID- 7793093 TI - [The effect of methyluracil polymorphism on lipid and antioxidant composition of rat tissues]. AB - The effect of two methyluracil forms on the composition of lipids, the content of peroxidation products and the amount of lipid-soluble scavengers of free radicals was studied in rat liver and heart tissues. Both these forms caused an increase in content of total lipids in the animal liver tissue 2 hrs after injection, whereas beta-form increased 1.6-fold the content of cholesterol esters and 1.9 fold that of triglycerides in liver tissue, unlike the alpha-form which affected these parameters slightly. The effect of methyluracil polymorphic derivatives on lipid peroxidation (TBA-positive products) was not detected. The methyluracil beta-form, not affecting the total pool of hydrophobic antioxidants, was found to decrease the content of active scavengers of free radicals in rat liver and heart tissues, as well as beta-form decreased the content of vitamin E in these tissues. At the same time, the methyluracil alpha-form did not affect the composition of tissue hydrophobic antioxidants. These differences found in the effect of two methyluracil forms on lipid composition and lipid-soluble scavengers of free radicals may be responsible for biological nonequivalence of the drug polymorphic forms. PMID- 7793092 TI - [Adaptation of renewal of rat liver proteins to dietary protein with low biological value]. AB - The study of the dynamics of adaptation to the rations containing casein and wheat protein showed some accumulation of hepatic protein on days 4-9. Evaluation of 14C-Leucine and protein turnover from the kinetics of precursor elimination from the pool and that of incorporation into proteins, demonstrated that there were no significant differences in the rate of endogenous protein synthesis, and the higher protein levels are associated with the lower secretion of these export proteins from the liver. In another experiment after adaptation to the casein feed, the animals were fed a wheat protein-containing feed, there were no changes in protein levels, yet the rate of total liver protein turnover was significantly increased on day 5, as shown by massive label estimation and calculation using the modified equation. Adaptation to new rations is accompanied by the initial accumulation of protein in the liver tissue and the subsequent adaptation to proteins of low biological value may be related to increases in the turnover of blood proteins exported from liver tissue. PMID- 7793095 TI - [The effect of Staphylococcus aureus toxic shock exotoxin on whole blood cell chemiluminescence in vitro and in vivo]. AB - Stimulated and nonstimulated blood chemiluminescence were studied in presence of the toxic shock syndrome toxin I (TSST-I) in vivo and in vitro. In vivo experiments involved evaluation of rabbit whole blood chemiluminescence developed within various periods after the TSST-I intraperitoneal administration. Effect of various TSST-I concentrations on blood chemiluminescence was studied in vitro. TSST-I was shown to inhibit the nonstimulated chemiluminescence in blood within 45 min after administration of LD50 of both opsonized zymosan and calcium ionophore A 23187 in vivo. Similar effects the toxin exhibited at concentrations 20 microM and more in vitro. The maximum effect TSST-I demonstrated within the first 5 min of incubation and this effect was distinctly dose-dependent. PMID- 7793094 TI - [Some biochemical indicators of the cytotoxic response of human fibroblasts cultured with natural and synthetic polycations]. AB - Cationic antiseptics--catamine AB, polysept (polymeric derivative of chlorhexidine) as well as cationic protein protamine exhibited a pronounced cytotoxic effect on human skin and lung fibroblasts in cell culture. Their effect was accompanied by augmentation of lipid peroxidation products and by inhibition of DT-diaphorase, LDH, ATPase and glutathione reductase. Introduction of alpha tocopherol into the cultural medium normalized the rate of lipid peroxidation but did not remove the inhibitory effect on activity of oxidoreductase studied. Blood serum proteins immunoglobulins and albumin diminished significantly the cytotoxic effect of cationic preparations contributing to restoration of all the parameters studied to control values; this phenomenon appears to occur due to nonspecific membrane protective and antioxidation effects of the blood serum proteins. PMID- 7793096 TI - [Immunoenzyme analysis of ferritin in diagnosing brain tumors]. AB - A procedure was developed to purify ferritin from the human brain tissue. The preparation is a heavy chain of ferritin. The level of ferritin in biological fluids was evaluated using the sandwich solid-phase immunoassay. This fraction of ferritin was found in the cerebrospinal fluid of patients with brain tumors. Content of the ferritin heavy chain in cerebrospinal fluid correlated with the rate of brain tissue malignancy. PMID- 7793098 TI - [Features of tissue oxygenation in patients with alimentary-constitutional and hypothalamic obesity]. AB - Tissue oxygen consumption was studied in 111 patients with alimentary constitutional and hypothalamic obesities. Polarography was used to study oxygen tension by means of oxygen and ischemic tests. Great impairments of oxygen consumption were found in the tissue of patients with hypothalamic obesity at the initial state, while in alimentary-constitutional obesity they increased during the oxygen test as the obesity progressed and was characterized by impairments of both oxygen supply and consumption, depending on the type of obesity. It is recommended to examine initial pO2 in the patients' skin as one of objective criteria for differential diagnosis of obesity. PMID- 7793097 TI - [Postoperative hypermyoglobinemia. Mechanism of occurrence. Predictive value]. AB - The time course of free myoglobin content and the rate of lipid peroxidation were simultaneously studied in cancer patients. The initial concentrations of myoglobin, hydroperoxides and malonic dialdehyde (MDA) were found to be higher than the control values, thus suggesting the increased rate of lipid peroxidation in these patients, which was responsible for destruction of cell membranes. Within the first 24 hours after surgery, there was a drastic release of myoglobin, its levels being sometimes higher in case of a complicated postoperative period than those in its smooth course. The increase in content of MDA was less marked, by reaching its maximum on days 1-2. The postoperative levels of hydroperoxides was considerably decreased, yet it began gradually increasing on day 2. The rather high correlation coefficients between the content of myoglobin and MDA suggest that there is a relationship between hypermyoglobinemia and the state of cell membranes. However, surgical intervention, enhancing lipid peroxidation, concurrently activates the mechanisms aimed at maintaining cell homeostasis. PMID- 7793099 TI - [Change in phospholipid composition of synovial fluid in children with various types of arthritis]. AB - Phospholipid composition of synovial fluid was studied in patients with reactive, rheumatoid and juvenile chronic forms of arthritis as compared with that of normal synovial fluid. The most pronounced alterations of the synovial fluid phospholipid composition (additional phospholipid fractions, increase in content of lyso-derivatives) were found in the patients with rheumatoid and juvenile chronic arthritis, which appear to occur due to activation of endogenous phospholipases A2, C and lysophospholipase A1. PMID- 7793100 TI - [Study of heat-protective effects of bromantane at various levels of overheating]. AB - The thermoprotective properties of bromantane were studied during overheating. Simultaneously with the known effects on heat exchange and sensitivity to high temperatures bromantane caused a decrease in ranges of heat tolerance, increased the rate of SVTK growth as well as altered protein metabolism and antioxidant protection and also affected the autonomic regulation of heat exchange which were essential in adaptation. At the same time, during ergothermal loading accompanied by any troubles in evaporation and heat exchange, marked thermoprotective efficiency of bromantane was compared for its ability to improve muscle dynamometry and hemodynamics as compared with control values. PMID- 7793102 TI - [Polarized immunofluorescent analysis of the herbicide isoproturon]. AB - Polarographic fluoroimmunoassay was developed for estimation of residual amounts of the herbicide isoproturon . The procedure is simple, accurate, highly sensitive and allows 10 preparations to be tested within approximately 7 min; the sample volume was 50 microliters and the low limit of the procedure sensitivity was about 0.2 micrograms/ml. The polarographic immunoassay may be used in screening express controls of isoproturon concentration in the sewage or in various extracts from various sources to control the herbicide contamination. PMID- 7793101 TI - [Change in the level of prostaglandins E and glutathione-S-transferase in leukocytes and plasma of hashish addicts]. AB - Content of prostaglandins E (PGE) as well as activity of glutathione-S transferase (GST) were studied in T lymphocytes, neutrophils and blood plasma of patients with hashishism as compared with healthy volunteers. Decrease in content of PGE was found in the blood cells studied but not in blood plasma of these patients, while distinct decrease of PGE by 40% occurred only in neutrophils. However, activity of GST was considerably decreased both in the cell fractions and blood plasma by 79-81%. The narcotic appears to affect the immunity system by means of the prostaglandin E metabolism impairment, thus suggesting the prostaglandin study in various immunity-related cells of the patients with narcomania. Besides, glutathione-S-transferase activity proved not to be a deciding factor affecting the prostaglandin content in leukocytes and blood plasma. PMID- 7793104 TI - KOBE declaration--the health paradigm for diabetes mellitus in the 21st century. PMID- 7793103 TI - [Production and some properties of covalent conjugates of total histone and kanamycin]. AB - A complex containing total histone and antibiotic kanamycin was produced under optimal conditions using glutaric aldehyde. The obtained water-soluble covalently bound conjugates of these substances were identified by means of enzyme labelled immunoassay and their molecular mass estimated. The validity of new class of highly effective drugs, which may be produced basing on the principles studied, was substantiated considering that histones exhibit the transport properties and are able to augment hematoencephalic barrier permeability. PMID- 7793105 TI - Systemic lupus erythematosus, rheumatoid arthritis and HLA phenotypes in Jamaicans. AB - The HLA phenotypes were investigated in 30 Jamaican patients with Systemic Lupus Erythematosus (SLE), 30 with Rheumatoid Arthritis (RA) and 40 healthy controls. HLA phenotypes were determined by the microcytoxicity technique, using commercially prepared typing trays. In this study, the HLA phenotypic associations with SLE (HLA-B14, RR 4.3: HLA-A28, RR 4.3) were not statistically significant. However, a statistically significant lack of HLA-A9 (p < 0.01; CP < 0.1) was observed in SLE patients compared to healthy controls. In RA patients, a statistically significant association was noted with HLA-A2 (RR 5.1; CP < 0.01). No HLA class II associations were noted with SLE. Class II associations with RA did not achieve statistical significance but included those previously established in other populations. The preliminary data obtained from this study indicate differences in the patterns of HLA phenotypes in Jamaican patients with SLE and RA compared to those observed in such patients elsewhere. Further studies involving larger groups of patients and typing at the serological, cellular and molecular levels are clearly warranted. PMID- 7793106 TI - Asymptomatic cardiac involvement in systemic lupus erythematosus. AB - Cardiologic and laboratory parameters were studied in 21 patients with systemic lupus erythematosus (SLE) with cardiopulmonary symptoms (CPS), 20 SLE patients without CPS and 45 age- and sex-matched healthy controls. The most frequent cardiac abnormalities in patients with CPS included pericardial effusion (24%), ventricular enlargement (20%), mitral regurgitation (19%) and tricuspid regurgitation (14%). No structural abnormalities were observed in SLE patients without CPS. Mean calculated and derived echocardiographic values in both groups of SLE patients differed significantly from those observed in normal controls (p < 0.004). Patients with CPS had significantly lower mean values of ejection fraction (p < 0.05) and fractional shortening (p < 0.03). However, the frequencies of functional abnormalities in patients with CPS did not differ significantly from those observed in patients without CPS. There were no remarkable laboratory findings in SLE patients with CPS compared to those without. The finding that some SLE patients may have functional cardiac abnormalities in the absence of CPS is an important one. It raises the question as to whether asymptomatic cardiac involvement in SLE is a separate entity or whether it heralds symptomatic cardiopulmonary involvement. PMID- 7793107 TI - Prevalence of exercise-induced asthma in schoolchildren in Kingston, St. Andrew and St. Catherine, Jamaica. AB - A cross-sectional study was done, focusing on the prevalence of exercise-induced asthma in Jamaica and variables that may account for this rate. No previous study of this nature had been undertaken, and the investigators contend that there is a need to identify children who suffer from this condition but are unaware of it. A sample of 214 students from primary and secondary schools in the Corporate Area were chosen and given questionnaires to complete. Eighty-four of the children reported a history consistent with that of exercise-induced asthma and were further subjected to stress testing for a definitive diagnosis of this condition. A prevalence of 20.8% [C.I. +/- 5.35] was identified which reflected a rate comparable to that recorded in North America. There was a significantly higher prevalence in children of primary school ages, but all other variables considered for significance testing to determine associations between these and the prevalence of EIA proved not significant. A recommendation has been made for opportunity screening by medical practitioners. PMID- 7793108 TI - Testosterone deficiency and extreme retardation of puberty in homozygous sickle cell disease. AB - Homozygous sickle-cell (SS) disease is associated with retardation of physical and sexual development but most Jamaican SS children commence their adolescent growth spurt before 16 years of age. Analysis of growth data from children in the Jamaican Cohort Study noted extreme growth retardation, defined as absence of the adolescent growth spurt and pre-pubertal sexual development (Tanner stage 1 or 2) at age 16 years, in 8/52 (15%) SS boys. These and two boys from the general sickle-cell clinic with a similar growth pattern provided a study group of 10 boys who were investigated for a possible endocrine explanation for their extreme retardation of physical maturation. A sub-optimal testosterone response (< 10 nmol/l) to human chorionic gonadotrophin and an exaggerated gonadotrophin response to gonadotrophin hormone releasing hormone was consistent with poor testicular function in 5 boys. Retardation of adolescent growth and development is common in boys with SS disease but, when extreme, requires early investigation to identify potentially correctable mechanisms. PMID- 7793110 TI - Socio-biological associations of bacteriuria in pregnancy. AB - The prevalence and socio-biological relations of bacteriuria in Trinidadian pregnant women were investigated. The prevalence of bacteriuria was found to be 16.7% and it was more common in the 30-39 year age group, among parous women, among Negroes, and in patients with a low family income and overcrowded living conditions. Symptoms were present in 19% of bacteriuric patients and almost one third gave a past history of urinary tract infection. Only 10% had been previously exposed to sexually transmitted diseases such as syphilis, gonorrhea and herpetic genital infections. Because of the serious consequences to mother and foetus, we advocate quantitative urine cultures for all antenatal patients, especially those coming from disadvantaged socio-economic conditions. PMID- 7793109 TI - Glyoxalase I activity in erythrocytes from severely malnourished children. AB - The enzyme glyoxalase I (Glyox I) is involved in metabolic detoxification, and requires glutathione (GSH) as a cofactor. Given the low concentration of whole blood GSH in children with oedematous malnutrition, it is possible that the function of this pathway may be compromised in these children. Glyox I activity was therefore assayed in erythrocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (+/- SEM) for the marasmic group (Marasmus: 105 +/- 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 +/ 4/u/gm Hb) were not significantly different from controls (Cont: 104 +/- 2 u/gm Hb). In the group with marasmic-kwashiorkor (M-K: 88 +/- 4 u/g Hb) Glyox I activity was significantly lower than in controls (p < 0.005), as well as in children with Marasmus (p < 0.005), and kwashiorkor (p < 0.05). Enzyme activity was lower than normal in 45% of the MK group. Seven children died subsequent to admission; in five cases Glyox I activities were exceedingly low. There was a weak positive correlation between Glyox I activity and whole blood levels of GSH (r = 0.215). We conclude that Glyox I activity is relatively unaffected in malnutrition, except in those with M-K and especially those who do not survive the acutely malnourished state. PMID- 7793111 TI - "Religio Medici" 1994. PMID- 7793112 TI - Acute carpal tunnel syndrome secondary to thrombosis of a persistent median artery. AB - An unusual case of thrombosis of a persistent median artery as a cause of acute carpal tunnel syndrome is reported. The sudden onset of numbness in the median nerve distribution and pain in the fingers were the main symptoms. The embryonic development of the median nerve vascular supply and the reported incidence of persistent median artery are reviewed. PMID- 7793116 TI - The influence of arginine-vasopressin on stool output and gastrointestinal transit time in healthy volunteers. AB - OBJECTIVE: It was asked whether continuous infusion of arginine-vasopressin (AVP) could decrease stool output and gastrointestinal transit time in healthy volunteers. DESIGN: Randomised single blind cross-over-design. SUBJECTS: 5 healthy male volunteers. INTERVENTIONS: Continuous s.c. infusion of AVP (7.5 micrograms/d) for one week vs. 0.9% NaCl-solution (placebo). Some days before the experiment started, the volunteers underwent a two-day-thirsting-period (< 500 ml/day). MEASUREMENTS: AVP-levels in serum, urine output, AVP-urine-excretion, stool frequency, stool weight, colonic transit time. RESULTS: As compared to saline infusion both serum-levels of AVP and AVP-excretion in urine were about four times higher during AVP-infusion whereas they were doubled during thirsting. Accordingly urine output was lower when AVP-levels were high. Parameters of colonic motility did not differ significantly (stool frequency 6.8 +/- 0.8/week for placebo vs. 6.8 +/- 0.5/week during AVP, stool weight 200.3 +/- 25.0 g/d vs. 210.6 +/- 21.1 gld, total colonic transit 22.9 +/- 7.0 hours vs. 25.7 +/- 5.8 hours). CONCLUSION: 1. AVP is well absorbed when applied subcutaneously. 2. AVP in the dosage given has no major influence on stool output and gastrointestinal transit time in healthy volunteers. PMID- 7793114 TI - Congenital solitary non-parasitic cyst of the liver. AB - Although non-parasitic cysts of the liver have often been described in adults, solitary non-parasitic cysts are rare in infants. We report a 17-month-old child with a large hepatic cyst. PMID- 7793113 TI - Tropical spastic paraparesis occurring in HTLV-1 associated infective dermatitis. Report of two cases. AB - An association between HTLV-1 infection and infective dermatitis (ID) a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis in two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-I infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection. PMID- 7793115 TI - Attitudes of medical students toward the acquired immune deficiency syndrome (AIDS). AB - Several studies have reported negative attitudes toward AIDS patients, homosexuals and drug abusers among physicians, nurses, and health workers in training. To examine attitudes towards AIDS of a group who in the near future would be practising physicians in the Caribbean, medical students at the Cave Hill Campus of the University of the West Indies were surveyed regarding their attitudes toward AIDS. This paper analyses responses to 21 Attitude Items with reference to five primary areas related to AIDS: Testing for HIV, Homosexuality, Fear of Contagion, Comfort in Interacting with AIDS Patients, and Intention to care for Persons with AIDS. The analysis indicates that these students were all not comfortable with issues related to homosexuality, and there was wide variation and some inconsistency in opinions regarding controversial and contentious issues. Most of these students, regardless of their choice of specialty after graduating, will eventually come into contact with an HIV positive individual or an AIDS patient. There is a distinct possibility that biases and misperceptions held during the period of training are at risk of being carried over into clinical practice, resulting in unwillingness, or even refusal, to treat certain types of patients. What has also become evident is that emphasis should be placed on ethical and attitudinal training within the Faculty of Medical Sciences. Our future doctors have to be trained to effectively manage the many psycho-social, ethical, and legal problems that will be generated by the AIDS epidemic. What is urgently needed, therefore, is relevant curriculum design and development in the area of AIDS Education directed at the region's future physicians. PMID- 7793118 TI - Helicobacter pylori eradication in the treatment and differential diagnosis of giant folds in the corpus and fundus of the stomach. AB - In an earlier study, we were able to show that giant fold gastritis is probably a special form of Helicobacter pylori-associated gastritis. Proof of this contention, however--namely regression of the giant folds following eradication of the organism--in a large number of patients was not then possible. To rectify this, Helicobacter pylori (HP) eradication treatment with omeprazole and amoxicillin was applied to 47 patients with HP gastritis and giant folds (5 patients with giant folds localized in the anterior or posterior wall, 42 patients with generalised giant folds within the corpus and fundus). The results of treatment were investigated by endoscopy and histology at the earliest 4 weeks after termination of treatment. In 40 of the 47 patients (85.1%), HP eradication treatment was successful. In 7 patients in whom treatment was unsuccessful, follow-up examinations revealed no changes in the endoscopic or histological findings. In 2 out of 3 patients in whom the endoscopic findings were unchanged despite successful HP eradication, biopsy material revealed the cause of the giant folds to be a signet ring cell carcinoma; in the remaining patient the cause of giant fold persistence was unclear. In 36 patients, the endoscopic- findings normalised completely, while in one patient there was obvious regression of the giant folds. We conclude from this study that giant fold gastritis is indeed a special form of HP gastritis, and that eradicating the organism in patients with gastric giant folds may help to distinguish between inflammatory, hyperplastic and tumorous giant folds. PMID- 7793117 TI - Relative risks of age, gender, nationality, smoking, and Helicobacter-pylori infection in duodenal and gastric ulcer and interactions. AB - A logistic regression model was applied to assess risk factors and diagnostic predictors in duodenal and gastric ulcer, as well as in unspecific changes of gastric mucosa. In the latter group smoking, epigastric distress, and pain were associated with elevated relative risks. In the gastric ulcer model, increased odds were found for age, German nationality, smoking, and low and high urease activity of antral mucosa. This holds for duodenal ulcer, too; however interactions between complaints, urease activity, and nationality must be considered. In each case odds depend from the composition of the control group. Therapeutic implications have been considered. PMID- 7793119 TI - [Laser lithotripsy of refractory bile duct calculi after failure of extracorporeal shock wave treatment]. AB - After failure of extracorporeal shockwave lithotripsy (ESWL) the benefit of further nonsurgical methods for treatment of difficult bile duct stones is undetermined. Endoscopic laserlithotripsy is a promising procedure providing target application of high energy levels. METHOD: Twenty patients (median age: 81 [67-91] years) were referred for laserlithotripsy of 1-8 (median, 2) difficult bile duct stones after failure of 1-4 (median, 3) ESWL sessions. The median diameter of each of the largest stone was 22 (10-48) mm. The laser used was a pulsed rhodamine laser (wavelength: 594 nm) with an automatic cut-out system upon no stone contact. The laser fiber was positioned by means of ERCP under fluoroscopic control or by use of mini-cholangio-scopes. Laserlithotripsy was cholangioscopically performed via the percutaneous transhepatic route in 8 patients because of retrogradely inaccessible bile ducts (n = 5) or because further ERCP was refused (n = 3). All procedures were carried out under intravenous sedation and/or analgesia. RESULTS: Laser lithotripsy and complete removal of fragments was achieved in 19 of the 20 patients after application of 70-25700 (median, 3310) pulses in 1.2 sessions per patient. Median duration of a single session was 70 (15-140) minutes. The procedure failed in one patient with an impacted stone at the cystic duct confluence. Cholangitis could be conservatively managed in 2 cases. No further complication was observed. The 30 day mortality rate was 0 %. CONCLUSION: Endoscopic laserlithotripsy is an effective, a rapid and safe procedure for bile duct stones even after failure of ESWL. The results compare favorably with open surgery, particularly in view of an increased risk in a group of elderly patients. PMID- 7793120 TI - Malabsorption associated with a high-grade-malignant non-Hodgkin's lymphoma, alpha-heavy-chain disease and immunoproliferative small intestinal disease. AB - We report on a 28 year old Turkish woman, who was admitted to our hospital with the symptoms of malabsorption and protein-loosing enteropathy. Histologically, on duodenal biopsy, a lymphoplasmacellular infiltration of the submucosa with partial to subtotal atrophy of the villi was found. An immunoproliferative small intestinal disease (IPSID) was diagnosed. A short remission whilst on a glutenfree diet and tetracycline therapy, was followed by a laparatomy because of ileus in the small intestine. A high-grade-malignant Non-Hodgkin's Lymphome of B cell type with intracellular production of alpha-Heavy-Chains (AHCD) was diagnosed histologically. Following chemotherapy with CEOP-IMVP-Dexa (Cyclophosphamide, Epidoxorubicin, Vincristine, Prednisolone, Ifosfamide, VP-16, Dexamethason, Methotrexat) the patient is still in complete remission three years after starting the therapy. We discuss here a case of AHCD in IPSID, the differential diagnosis of protein losing enteropathy and malabsorption, and we also present conservative (diet, medical treatment) and operative therapies. PMID- 7793122 TI - [Neuroimmune interactions in the gastrointestinal tract]. AB - The enteric nervous system and immune system are integrated systems that play an important role in the regulation of gastrointestinal functions. Recent studies suggest a bidirectional interaction between both systems. The relationship is based on the synthesis and release of neuropeptides from immune cells and the receptor-mediated alteration of nervous and immune functions by neurotransmitters and inflammatory mediators. The activity of the enteric nervous and immune system can be modulated by the central nervous system. These psycho-neuro-immuno interactions are involved in gut inflammation, in functional bowel diseases and in the physiological control of gastrointestinal functions. PMID- 7793123 TI - [Insulin promotor factor I (IPF-I) is an essential factor during development of the pancreas]. PMID- 7793124 TI - [Gene transfer in the gallbladder]. PMID- 7793121 TI - [Nonobstructive mesenteric ischemia--a diagnostic problem in internal intensive care]. AB - Four cases of acute gut ischemia in elderly patients due to non-occlusive disease (NOD) are presented. Bowel necrosis occurred after episodes of hypotension in the course of myocardial infarction, arrhythmias and sepsis. Symptoms and clinical findings were blurred by the underlying extraintestinal disease. Angiography showed coexistent atherosclerosis but no occlusion of the major celiac and mesenteric vessels. At laparotomy (three cases) or autopsy (one case) extensive small and large bowel necroses were detected. Early laparotomy (possibly preceded by laparoscopy) is recommended for patients with suspected acute gut ischemia even if angiography fails to reveal occlusion of the large splanchnic arteries. PMID- 7793125 TI - 6th Workshop for experimental and clinical liver transplantation and hepatoloy. Wilsede, 18-20 May 1995. Abstracts. PMID- 7793126 TI - Priming and induction of anti-rotavirus antibody response by synthetic peptides derived from VP7 and VP4. AB - Synthetic peptides derived from bovine rotavirus C-486 (BRV) outer capsid (VP7 and VP4) and inner capsid (VP6) proteins were tested to evaluate their ability to prime and induce an anti-rotavirus antibody response. Peptides corresponding to the amino acid residues 232-255 of VP4 (VP4-peptide), 275-295 of VP7 (VP7 peptide) and 40-60 of VP6 (VP6-peptide) of BRV were chemically synthesized. These peptides were coupled to carrier proteins (either keyhole limpet haemocyanin (KLH) or recombinant rotavirus inner capsid protein-VP6 assembled into virus-like particles (VP6-carrier) were used as carrier to link the synthetic peptides under study), and the resulting conjugates were used to immunize rotavirus seronegative mice. An enzyme-linked immunosorbent assay (ELISA) was used to determine anti peptide and anti-rotavirus antibody titres in serum samples collected after immunization. All peptides were immunogenic in mice and induced the production of anti-peptide antibodies, but with the exception of VP6-peptide they were not able to induce anti-rotavirus antibodies as measured by ELISA. Western blot analysis indicated that antibodies against each peptide were able to react with the respective authentic viral proteins of various rotavirus serotypes. To determine if a peptide-primed animal would respond to native viral proteins, animals were subsequently injected with purified BRV. A rapid and high anti-rotavirus antibody titre, in addition to a rise in anti-peptide antibody titre, was observed in peptide-primed mice. Furthermore, the sera obtained from these mice neutralized the virus under in vitro conditions. The significance of these results in relation to a potential rotavirus synthetic peptide-based vaccine is discussed. PMID- 7793127 TI - Mechanism of enhancement of the immune responses to influenza vaccine with cholera toxin B subunit and a trace amount of holotoxin. AB - Cholera toxin B subunit (CTB) (1 microgram) and a trace amount of cholera toxin (CT) (0.1-10 ng), when inoculated intranasally into Balb/c mice together with influenza vaccine, induced synergistically a greater delayed-type hypersensitivity (DTH) response to the vaccine than did a trace amount of CT alone. In parallel with the in vivo response, normal peritoneal macrophages that were incubated in vitro with the vaccine and the CT-containing CTB, induced a higher adenylate cyclase activity and a greater ability to transfer DTH response into naive recipient mice than did the macrophages incubated with the vaccine and CT. The treatment of macrophages with the vaccine and CTB failed to induce either adenylate cyclase or DTH response. From these results, the mechanism by which CTB and a trace amount of CT enhance immune responses synergistically could be explained by the enhancement of the CT action on macrophages or by the efficient binding of a trace amount of CT to antigen-presenting cells in the presence of a relatively large amount of CTB, resulting in enhanced cyclic AMP formation followed by enhanced antigen presentation. PMID- 7793128 TI - An inactivated vaccine based on a glycoprotein E-negative strain of bovine herpesvirus 1 induces protective immunity and allows serological differentiation. AB - The bovine herpesvirus 1 (BHV1) strain Za is a conventionally attenuated strain with a 2.7 kb deletion that encompasses the complete coding region for glycoprotein E (gE). This gE-negative strain was used as whole-virus antigen in an inactivated virus vaccine. Three different antigen concentrations of this vaccine were evaluated for safety and efficacy in a vaccination-challenge experiment in calves. No adverse effects were observed in any of the calves vaccinated with the gE-negative vaccines. Calves given the vaccine with the highest antigen concentration were adequately protected against challenge; clinical symptoms were virtually absent and challenge virus shedding was significantly reduced as compared with unvaccinated calves. We developed a sensitive blocking enzyme-linked immunosorbent assay (ELISA) to detect antibodies against gE. After vaccination, calves did not produce antibodies against gE, but these antibodies were detectable within 2 weeks after challenge both in vaccinated and in unvaccinated calves. These results demonstrate the efficacy of a gE-negative inactivated BHV1 vaccine and the detectability of antibodies against gE after infection. The combined use of the marker vaccine and the gE blocking ELISA makes it possible to differentiate between vaccinated animals and infected animals. This possibility may be very useful in BHV1 control programmes. PMID- 7793129 TI - Eimeria maxima gametocyte antigens: potential use in a subunit maternal vaccine against coccidiosis in chickens. AB - Affinity-purified gametocyte antigens (APGA) from Eimeria maxima, emulsified in Freund's adjuvant, were injected intramuscularly into breeding hens on two or three occasions. As a result, progeny of the immunized hens were partially immune to infection with E. maxima, Eimeria tenella and Eimeria acervulina (with a reduction in total oocyst output of 45-63% as compared with progeny of untreated hens). Thus, APGA in Freund's adjuvant appears to have great potential as part of a maternally applied vaccine against coccidiosis. The ability of APGA to induce partial cross-species protection is most probably due to the existence of conserved epitopes in the different species as indicated by comparative Western blots of E. maxima and E. tenella. Surprisingly, Freund's adjuvant by itself also induced significant levels of maternal immunity to coccidiosis (with a 12-35% reduction in oocyst output in the progeny). In contrast to the purified antigens or Freund's alone, crude extracts from gametocytes as well as other developmental stages, induced little if any significant maternal immunity despite provoking the production of large amounts of parasite-specific IgG, including antibodies to APGA. This result indicates that a successful maternal vaccine against coccidiosis requires, in addition to good recognition of protective antigens, the exclusion of irrelevant antigens from the vaccine preparation. PMID- 7793130 TI - Does the HIV-1 manipulate immune network via gp120 immunoglobulin-like domain involving V3 loop? AB - According to the multiple criteria used, the consensus sequences of HIV-1 gp120 and immunoglobulin heavy chain variable segment, which is more than 40 amino acids long, show structural similarities. We assume that this gp120 sequence might encode idiotopes. If this is the case then the particular idiotope-bearing gp120, either soluble or expressed in multiple form on the surface of the infected cell, can influence the immune response in idiotype(Id)-anti-Id fashion. This might be the mechanism by which HIV induces immunological abnormalities and it should be taken into consideration in vaccine production as suggested by the authors previously. PMID- 7793131 TI - Detection of Newcastle disease virus in poultry vaccines using the polymerase chain reaction and direct sequencing of amplified cDNA. AB - In order to develop an in vitro method for the control of poultry vaccines for identity and the absence of extraneous agents, reverse transcription-polymerase chain reaction (RT-PCR) was applied for the detection of Newcastle disease virus (NDV). NDV vaccines were employed for the establishment of the method, using two primer pairs spanning the cleavage site of the F0 fusion protein coding sequence. Amplification of a specific cDNA segment was possible from live and inactivated, oil-adjuvanted NDV vaccines without prior treatment. The cDNA was characterized by restriction endonuclease digestion as well as by direct nucleotide sequencing. The RT-PCR was able to detect between 5 x 10(2) EID50 (in live vaccine preparations) and 10(5) EID50 or 0.056 haemagglutinating units of NDV (in inactivated vaccine preparations). In addition, live vaccine preparations were inactivated with beta-propiolactone (beta-PL). Amplified cDNA was obtained after treatment with 0.1% beta-PL, whereas at a concentration of 1% or 10% no specific bands were visible in the agarose gel. These results demonstrate the applicability of the method for the control of poultry vaccines for identity and for the absence of extraneous agents, and additionally allow a rapid characterization of the respective NDV strain. PMID- 7793132 TI - Influenza immunization policies in Europe and the United States. AB - Influenza vaccination policies of 28 European countries were compared with those of the US Immunization Practices Advisory Committee. Twenty-four of 28 (86%) European countries had immunization policies for influenza. European and US recommendations were in complete agreement concerning immunization of those with heart and lung disease. Within Europe there was 81-86% agreement concerning immunization of the elderly, irrespective of their health status, and patients with diabetes, renal dysfunction and immunosuppression, and 71% agreement concerning those in residential care and occupational groups that can transmit influenza to high-risk patients. Unlike the US, 62-71% of European countries did not target those with haemoglobinopathies, children and teenagers taking salicylates or household members of those at high risk. Few recommendations were endorsed by relevant medical or patient organizations. The observed variation in vaccination policies in Europe and North America possibly reflect uncertainties concerning risks from influenza and benefits from vaccination, and differences in public health systems and attitudes towards preventive medicine. PMID- 7793133 TI - Characterization of measles viruses isolated after measles vaccination. AB - Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles. PMID- 7793134 TI - A reduced dose approach to hepatitis B vaccination for low-risk newborns and preschool children. AB - The effectiveness of a 2.5 micrograms dose of the hepatitis B vaccine (B-Hepavac II) was compared with that of 5 micrograms in 587 low-risk neonates and 777 preschool children of age 3-8 years. The vaccines were administered at months 0, 1 and 3, with postvaccination serology tested at months 4 and 12. The seroconversion rates of the 2.5 microgram recipients (newborn: 93.5%; preschool children: 97.4%) are comparable with the 5 micrograms group (newborn: 95.7%; preschool children: 98.7%). The seroconversion rates of the newborns are, however, significantly lower in the 2.5 micrograms group if positive response is taken as a titre > 10 IU l-1, instead of > 0 IU l-1. The older children, on the other hand, achieved a higher seroconversion rate and geometric mean titre (GMT) when compared with the newborns. irrespective of the dose received. PMID- 7793135 TI - Influenza immunization for HIV-infected persons in Los Angeles. AB - We assessed the use of influenza vaccine in a cohort of HIV-infected patients during 1991 and 1992 in Los Angeles County. Influenza vaccination status and clinical and demographic data were obtained from medical records in three different outpatient clinics: a health maintenance organization (HMO), a public clinic and a private medical group. The overall proportion of patients immunized with influenza vaccine was 28%. Patients receiving medical care at the HMO were more likely to receive influenza vaccine (45%) than were patients at the public clinic (25%) or the private facility (13%). Higher immunization levels were also observed among patients with greater numbers of clinic visits for both years studied (p < 0.001). After we controlled for the number of outpatient visits, patients at the HMO and the public clinic were still more likely to receive influenza vaccine in both 1991 (adjusted relative risks 3.2 and 2.1, respectively) and 1992 (adjusted relative risks 1.7 and 1.8) compared with private clinic patients. Health-care providers should increase efforts to provide influenza vaccine to HIV-infected patients. PMID- 7793136 TI - The effect of Escherichia coli J5 and modified live Salmonella dublin vaccines in artificially reared neonatal calves. AB - One thousand neonatal calves, allocated in a factorial design into four groups, were vaccinated subcutaneously with two doses each of either killed Escherichia coli (0111:B4) J5 bacterin or a UC Davis modified live, genetically altered (aro ) Salmonella dublin vaccine, or both, or with a placebo. In this prospective double-blind study to determine the immunogenicity and protective effects of both vaccines on bovine neonates in field conditions, calves were observed daily until 2 months of age, and serum samples from selected study calves were obtained at five different time points. No clinical adverse vaccine reactions were observed. Overall mortality was 7.5% (75 of 1000), E. coli and S. dublin infection being the most commonly associated aetiological agents of deaths. Both J5 (p < 0.01) and Salmonella (p = 0.05) vaccines were significantly effective in reducing the mortality rate but without an additive effect. The role of passive transfer was important in calf survival. The E. coli J5 and (aro-) S. dublin vaccination schedule employed significantly (p < 0.001) elevated J5 and Salmonella-specific serum ELISA antibody titres, respectively, by the sixth week of age. PMID- 7793137 TI - Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in Balb/c mice that are similar to those generated by experimental infection. AB - The feasibility of employing a vaccine composed of the purified fraction 21 of Quillaja saponaria (QS-21) and the fusion (F) protein of respiratory syncytial virus (RSV) to induce protective immune responses in the lower respiratory tract of Balb/c mice was examined. Our goal was to compare local and systemic immune responses with those induced following immunization with the protein adsorbed to aluminium hydroxide (F/ALOH) adjuvant or by experimental infection. Sera from mice vaccinated with the QS-21 formulation (F/QS-21) contained elevated anti-F protein IgG antibody titres that were dependent on the dose of QS-21 employed. Similar to the immune responses generated by experimental infection, the sera from mice vaccinated with F/QS-21 possessed greater capacity to neutralize virus infectivity that was associated with the generation of heightened complement fixing IgG2a antibody titres. In contrast, vaccination with F/ALOH elicited systemic immune responses that were characterized by a predominance of protein specific antibodies of the IgG1 subclass and lower neutralizing antibody titres. The capacity of F/QS-21 to facilitate local pulmonary immune responses was also examined and found to be similar to those induced by experimental infection. After virus challenge, a 90-fold increase in the number of F protein-specific antibody-secreting cells was observed and associated with the clearance of virus from the infected lungs. Moreover, elevated levels of antigen-dependent killer cell activity were detected and appeared to be mediated by class I major histocompatibility complex restricted CD8+ T cells. Additional characterization of the pulmonary immune response was performed on the cellular infiltrates obtained after bronchoalveolar lavage and on formalin-fixed lung tissue. The local protective immune responses induced after challenge of the groups immunized with F/QS-21 or infectious virus were significantly different from those elicited in naive control mice injected with adjuvant alone, or in mice immunized with F/ALOH. The cellularity of the lavage fluids from the former groups was characterized by a significantly greater percentage of lymphocytes and less neutrophils. In similar fashion histological evaluation of the lungs from mice immunized with F/QS-21 or infectious virus revealed significantly elevated local immune responses after challenge. In conclusion, the results suggest that formulation with F/QS-21 alters the qualitative and quantitative nature of the immune response to the F glycoprotein when compared with the traditional aluminium-based adjuvants. PMID- 7793139 TI - Stimulation of rotavirus IgA, IgG and neutralising antibodies in baboon milk by parenteral vaccination. AB - A rhesus rotavirus vaccine adjuvanted with ISCOMs was injected intramuscularly to 5 pregnant baboons, with repeated doses 1-2 and 14 weeks after delivery. Maternal blood and milk samples and blood samples from their babies were collected at 2 weekly intervals until 26 weeks after parturition. Samples were assayed for rotavirus antibodies by ELISAs and neutralisation tests. Vaccination produced statistically significant increases in maternal serum IgG and neutralising antibodies, and in milk IgA, IgG, and neutralising antibodies. Control baboon mothers sampled from 12 weeks after delivery had lower serum and milk antibody titres, but responded to vaccination at 16 weeks by producing a similar antibody profile in serum and milk to those previously vaccinated. Because of the endemic nature of human rotaviral infections, similar maternal vaccinations have potential as a means of increasing milk antibodies to a level at which they may be protective to infants. PMID- 7793138 TI - Construction of Neisseria meningitidis strains carrying multiple chromosomal copies of the porA gene for use in the production of a multivalent outer membrane vesicle vaccine. AB - Starting with Neisseria meningitidis strain H44/76, a set of strains was constructed for use in production of a multivalent outer membrane vesicle vaccine. The aim was to remove unwanted outer membrane components and at the same time to improve the range of protection. This was accomplished through transformation with plasmid constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome. Deletion of the cps locus resulted in loss of expression of the group B capsular polysaccharide as well as the lacto-N-neotetraose structure in lipopolysaccharide. Deletion of the porB gene abolished expression of the class 3 outer membrane protein. Additional copies of the porA gene, encoding the immunodominant class 1 outer membrane protein, were inserted into one of the opa genes and into the rmpM gene encoding the class 4 outer membrane protein. This construction was done with three sets of porA alleles, resulting in three trivalent strains, each of which expressed a different combination of class 1 epitopes. PMID- 7793140 TI - Current approaches to the development of vaccines against disease caused by respiratory syncytial virus (RSV) and parainfluenza virus (PIV). A meeting report of the WHO Programme for Vaccine Development. AB - The paramyxoviruses respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are the two most common agents of severe lower respiratory tract disease in infants and children throughout the world. RSV causes yearly epidemics of bronchiolitis and pneumonia in infants and young children, while PIV3 is a common cause of bronchiolitis, pneumonia and croup. Together these two agents account for up to 30% of all hospitalizations of infants and young children for respiratory tract disease. A licensed vaccine is not currently available for either of these viruses. Development of vaccines against diseases caused by RSV and PIV3 is one of the priorities of the Global Programme for Vaccines (GPV). On 27 March 1994, GPV sponsored a workshop in Nyon, Switzerland, to review the status of vaccine development for these pathogens and to explore new methods of immunization that might be applied to the prevention of diseases caused by RSV and PIV. Furthermore, the World Health Organization (WHO) wished to assess progress in the development of methodologies to rescue infectious virus from cDNA clones of RSV and PIV3. This technology, when developed, will be extremely valuable in developing new vaccine candidates and in unravelling the genetic basis of attenuation of existing vaccines. This paper summarizes the findings presented at this one-day meeting. PMID- 7793142 TI - [Subclavian vein thrombosis: epidemiologic data of the PHLEKO (phlebothrombosis conservative treatment) Study]. AB - This is a report of 91 cases of subclavian vein thrombosis. The data are derived from the PHLECO-study (Phlebothrombosis-Conservative treatment) which is a multicenter investigation on the fate of 2088 deep vein thromboses as diagnosed by phlebography. In this cohort the subclavian vein thrombosis incidence was recorded at 4.36%. The interval between first symptoms and hospital admission lasted 3.90 days. The average patient's age was 46.3 years. The genders were evenly distributed. The causes of subclavian vein thromboses were in 29.7% traumatic (effort thrombosis, catheter manipulation), in 31.9% symptomatic (accompanying other diseases), and in 38.4% idiopathic (cause unknown). Fibrinolytic therapy was carried out in 49.4% of the cases, the remainder received anticoagulants. Patients with acute subclavian vein thrombosis and conservative treatment (no fibrinolytic therapy) stayed for 18.8 days in the hospital. No instances of pulmonary embolism, either fatal or non-fatal, were recorded. PMID- 7793144 TI - Vascular injuries in Sweden 1986-1990: the result of an enquiry. AB - In order to review the management of vascular trauma in Sweden all surgical and orthopedic departments were asked to report retrospectively vascular injuries occurring between 1986 and 1990. There were 294 injuries reported from 55 departments. The majority (approximately 80%) of the injuries were confined to the extremities. In the arms the injuries of the vessels were mostly simple, whereas in the legs they were more complex and correct treatment demanded extensive experience in vascular surgery. No less than 20% of the injuries were iatrogenic and half of them required reconstructive surgery. 55% of the iatrogenic injuries occurred during angiological examinations and treatments. Complex vascular injuries are often combined with fractures and soft tissue damage and required close cooperation between vascular and orthopedic surgeons. Advanced angiological examinations and treatments should only be performed in hospitals with vascular surgery facilities. PMID- 7793141 TI - Guidelines for therapeutic studies in Fontaine's stages II-IV peripheral arterial occlusive disease. German Society of Angiology. PMID- 7793143 TI - The incidence of postoperative deep vein thrombosis in vascular procedures. FINNVASC Study Group. AB - This survey aimed to estimate the rate of deep venous thrombosis (DVT) in an unselected population treated for peripheral vascular diseases. The study comprised 7533 patients on the nationwide Finnish vascular registry (FINNVASC) during two-years study period. Thirty-four (0.45%) patients were reported to have a postoperative thrombosis. Thirty-two (94%) of these had undergone vascular procedures involving the infrarenal aorta or arteries in the lower extremities. There was no difference in the occurrence of determinants (diabetes, hypertension etc.) when the group with postoperative DVT was compared to the rest of the patients on the registry. The procedures involving the lower extremity seem to carry a higher risk of postoperative DVT. In this type of surgery special attention should be focused on DVT prophylaxis. PMID- 7793145 TI - [The diagnostic value of angioscopy in venous thrombectomy]. AB - Since 1983 angioscopy was applied as a control method in 187 venous thrombectomies to improve the treatment of acute iliofemoral thrombosis. In a retrospective study we tried to show the impact of angioscopy intraoperatively and the influence on long-term results. Thrombectomy was performed in 97 patients affected at three levels, in 50 cases with pelvic-femoral, in 35 with pelvic and in 43 with femoro-tibial thrombosis. The average clinical age of the thrombosis was 5 days, 66% of the patients (age 39 years) were female. The endoscopic findings were compared with phlebological results after one year using a phleboscore between 0 points (occlusion) and 5 points (normal). The phlebographies were analyzed so that the functional status of the vein was represented. After venous thrombectomy 42.8% of the cases were endoscopically classified complete but in 57.2% residual clots were observed. It was possible to completely (24.6%) or partly (18.7%) remove these clots by further thrombectomy maneuvers, non removable remnants were found in 7.5% and a venous spur in 6.4%. The statistical analysis with Kruskal-Wallace test showed significant differences in venous morphology between the endoscopically complete thrombectomies and those with residual clots. After a follow-up period of 30 months (12-64) the clinical results were very good. In 58% we observed normal findings, a cvi grade I in 35%, grade II in 4%. Crural ulcers had developed in only 3%. From our data we conclude that endoscopy is an excellent method for intraoperative quality-control in venous thrombectomy. PMID- 7793146 TI - [Metabolic effects of intermittent exercise by patients with stage II arterial occlusive disease]. AB - During intermittent exercise lasting six minutes with two minutes' rest the fluctuations in arterial and venous blood of lactate, pyruvate and blood gases as well as changes in the lactate pyruvate ratio were studied in eleven patients with intermittent claudication. There were significant differences of O2 extraction during intermittent exercise. The level of arterial lactate did not vary significantly. The highest venous lactate was found during the rest period. Significant differences in venous lactate, pyruvate and lactate pyruvate ratio were found between the first and second exercise periods. It is assumed that the rate of glycolysis is reduced during intermittent exercise. PMID- 7793147 TI - [Reactive hyperemia after arterial occlusion: comparison of infrared telethermography and laser Doppler flowmetry]. AB - Before, during and after arterial occlusion we measured Laser-Doppler Flux (LDF) and skin temperature using Infrared-Thermographie (IRT) in 40 healthy adults (20 female, 20 male). In the region of the hypothenar eminence of the left hand LDF and skin temperature showed significantly higher values in male compared with female subjects prior to occlusion (p < 0.01 resp. p < 0.05). After arterial occlusion for 120 seconds LDF showed a significant overshoot of 71.3% (+/- 39.5%) above baseline. During this phase of hyperemia skin temperature rose from 33.5 to 34.8 degrees C (p < 0.0001). This reaction was similar in men and in women. Changes in skin temperature were slower and more prolonged compared with the rapid changes of LDF. The absolute temperatures were significantly higher when we used IRT compared with temperatures measured by resistance thermometry. Both methods showed a close correlation (p < 0.0001, r = 0.891). Using the IRT technique a large number of skin temperatures can be measured simultaneously and temperature changes can be detected and visualized by colour thermograms. Postocclusive cutaneous hyperemia induces similar responses in LDF parameters and in skin temperatures. IRT therefore could be used as an additional tool for the assessment of physiological and pathological functions of the cutaneous microcirculation. PMID- 7793148 TI - Neutrophil-derived adhesion molecules in human digital ischaemia and reperfusion. AB - In order to see whether leucocyte-derived adhesion molecules are involved in ischaemia and reperfusion, the total and differential leucocyte counts and expression of the LFA complex i.e. CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p 150,95) were monitored before and after standard cold and heat tests in 8 females with Raynaud's Disease and 8 matched controls. All patients suffered from vasoconstriction during the cold test which, compared with controls, was associated with fewer granulocytes expressing significantly more CD11b/CD18 (Mac-1) integrin and a significant degree of neutropenia persisting during reperfusion. Leucocyte-endothelial adhesive interactions may therefore occur during ischaemia and reperfusion. PMID- 7793149 TI - [Reconstruction of brain-supplying arteries with bilateral monitoring by transcranial Doppler ultrasound--new aspects for technical surgical procedures]. AB - From January to June 1994 reconstruction of 61 internal carotid arteries (ICA) with cerebral monitoring using bilateral transcranial Doppler sonography in the Clinic of Vascular Surgery Charite was performed. Recording of the maximal mean blood flow velocity in both middle cerebral arteries (MCA) was performed intraoperatively. After clamping of ICA flow velocity in the ipsilateral MCA decreased immediately but recovered within short time in 60% of our patients (Vmean > 25 cm/s). Based on the reaction of the contralateral MCA 3 types were differentiated: 1) Vmean of the contralateral side changed contrary to the ipsilateral side (compensation, "scissors type"). 2) The contralateral side did not react ("indifferent type"). 3) The contralateral side changed parallel to the ipsilateral side ("parallel type"). In 62% of our patients the operative strategy was influenced by transcranial Doppler monitoring: in 35% of cases the operative reconstruction was performed without intraluminal shunting, in 19% of cases the position of the intraluminal shunt was corrected, in 8% of cases the blood pressure was increased. Doppler signals due to emboli were registered in 43% of our patients. These patients did not show any new neurologic signs and symptoms. In one patient who developed a neurological deficit during the postoperative phase, emboli signals were recorded during a period of 30 minutes. Bilateral transcranial Doppler monitoring, especially in patients with contralateral high grade stenoses or occlusions of the ICA, is a useful method for intraoperative cerebral monitoring. We recommend its application on a wide scale. PMID- 7793150 TI - [Cerebral oximetry by infrared spectroscopy in comparison with continuous measurement of oxygen saturation of the jugular vein bulb in interventions of the internal carotid artery]. AB - OBJECTIVE: Monitoring the central nervous system during carotid endarterectomy plays an important role in detection of cerebral ischemia. With optical spectroscopy in the near-infrared light range it is now possible to measure regional cerebral oxygen saturation (rSO2) noninvasively. Numerous studies emphasize the importance of cerebral oxygen balance rather than absolute values of cerebral blood flow or metabolic rate. In this study data from oxygen saturation measured in the jugular bulb (SJO2) were compared to rSO2. METHODS: 10 patients undergoing elective carotid end-arterectomy were enrolled after written informed consent and approval by the local ethics committee. rSO2 data were measured by cerebral spectroscopy (INVOS 3100, Somanetics, Michigan/USA). To avoid lesions of the internal carotid artery, a 4-F oxymetry catheter (OPTICATH, Abbot GmbH, Wiesbaden) was placed in the jugular bulb by retrograde approach after preparation by the surgeon. Anaesthesia and mechanical ventilation were standardised. RESULTS: After cross-clamping of the internal carotid artery rSO2 significantly decreased (60.5 +/- 3.5%) compared to baseline (66.0 +/- 1.4%). After declamping rSO2 increased significantly (63.0 +/- 4.2%) and was close to baseline at the end of operation (65.0 +/- 2.8%). The SJO2 time course showed good correlation compared to rSO2 data (r = 0.85). After cross-clamping SJO2 decreased significantly (51.5 +/- 6.3%) in comparison to baseline (59.5 +/- 4.9%). Declamping increased SJO2 to 59.5 +/- 6.3%. No changes in latencies or amplitudes of SEP were observed throughout the operation. CONCLUSIONS: Noninvasive cerebral optical spectroscopy is a useful tool to determine the brain tissue oxygenation. The positive correlation to jugular bulb oxygen saturation is somewhat unexpected as rSO2 evaluates regional while SJO2 measures global oxygen content. However our results suggests that both methods are able to detect episodes of cerebral ischemia during carotid endarterectomy. The interpretation of the changes of cerebral oxygen saturation with respect to neurological outcome warrants further studies. PMID- 7793151 TI - [Determination of the degree of stenosis of the internal carotid artery in the surgical specimen after eversion TEA: comparison with angiography and c-w-Doppler ultrasound]. AB - 22 carotid specimens following eversion-endarterectomy were compared with preoperative assessment of carotid stenosis obtained angiographically and by c-w Doppler-sonography. The intact, unsplit specimens were perfused with a liquid plastic material (Palavit M). After hardening of the plastic material the specimens were removed. The local degree of carotid stenosis with respect to diameter reduction was assessed by direct measurement of the plastic specimens at the narrowest site compared with the diameter of the carotid eversion specimens at the place of the maximum stenosis. The distal degree of carotid stenosis was assessed by comparison of the diameter of the distal internal carotid artery obtained intraoperatively with the measurements of the plastic specimens (1 mm vascular wall thickness of distal internal carotid artery was taken into account). RESULTS: Both the local and the distal degree of carotid stenosis diameter (mean 84.7% +/- 8.4% and 82.1% +/- 9.1% respectively) were underestimated in the preoperative angiogram (79.8 +/- 9% by ECST-criteria and 69 +/- 10.3% by NASCET-criteria) in most of the cases. The difference of the diameter reduction was statistically significant (p < 0.05 and p < 0.01 respectively, Wilcoxon signed rank test). The c-w-Doppler assessments were 82.6 +/- 8.2% (n.s.). CONCLUSION: Our results suggest that the preoperative assessment of internal carotid stenosis obtained angiographically or by c-w-Doppler sonography easily underestimate the true degree of carotid stenosis. PMID- 7793152 TI - [Experimental aortic aneurysm with endovascular technique]. AB - We created a simple experimental aneurysm by a minimal operative trauma performing the balloon-dilatation and the rupture of the abdominal aorta of animals. The aorta of minipigs was dilated under angiographic control until the rupture became visible. The abdominal aorta and its branches were mapped out and measured. The angiographics were calculated using a planimetric device. The dilatation of the aorta was increased up to 3.5 times the initial diameter when rupture occurred. The microscopical examination showed lesions in all three layers of the vessel only at the rupture site and some focal lesions of the tunica intima. This one-step procedure of producing an experimental aneurysm is done using a low operative trauma and allows testing of endovascular systems using only one anaesthetic. PMID- 7793154 TI - Fibromuscular dysplasia causing atypical coarctation of the thoracic aorta: histological presentation of a case. AB - The authors report a case of atypical coarctation of the thoracic aorta discovered by chance in a 37-year-old man, victim of a car accident. The angiogram revealed a "string-of-beads" contour in the coarctate area while the left subclavian artery presented a severe stenosis at its origin. Vascular checkup examination failed to identify any additional vascular anomaly. The patient underwent surgical resection, with a Dacron prosthetic bypass. Histological study of the specimen removed, showed a typical perimedial and extensive medial types of fibromuscular dysplasia (FMD) of the aorta. Pathogenesis of this disease is discussed. PMID- 7793153 TI - [Media sclerosis: a case of pseudohypertension]. AB - A 51-year-old diabetic showed symptoms of a hypertensive crisis with a systolic blood pressure above 300 mmHg. The antihypertensive therapy failed and the Doppler-pressure values were also too high for all limb arteries. Duplex sonography and soft-x-ray examination showed a mediasclerosis of arms and legs. The true pressure, measured at the still compressable arteries of the fingers was relatively low. There was symptomatic improvement after completion of the antihypertensive therapy. PMID- 7793155 TI - Diagnosis of acute aortic occlusion by computer tomography. AB - We present a case of acute aortic occlusion, which was diagnosed immediately with CT. Since a prompt diagnosis is essential we recommend contrast enhanced CT as a quick procedure to confirm diagnosis and to exclude dissecting thoracic aneurysm and genuine abdominal aneurysm. PMID- 7793157 TI - [Combination therapy in chronic polyarthritis]. AB - Long-term effects of disease-modifying antirheumatic drugs are not at all satisfactory. Therefore combinations of different substances have long been studied. But no convincing recommendations could be derived from those results. Some combinations seem to be more effective than the single substances, but often have more side-effects. First of all, those types of rheumatoid arthritis must be defined which require an aggressive therapy. These may profit from combinations with sulfasalazine, methotrexate or azathioprine. But such questions may only be answered by long-term studies which can be statistically evaluated. PMID- 7793158 TI - [Innervation of the sacroiliac joint of the human]. AB - The innervation of the human sacroiliacal joint was investigated on adult cadaveric specimens devoted for routine dissection courses, and on fetuses obtained from therapeutic abortions. Gross anatomical and microscopic dissection, histology of dissected nerves, and histological and immunocytochemical approaches were used. Innervation of the iliosacral joint is provided by fine nerve branches derived exclusively from dorsal rami of spinal nerves S1-S4. No branches could be detected from the plexus sacralis and obturator nerve coursing over the ventral aspect of the joint. Nerves were distributed to superficial and deep dorsal sacroiliac ligaments, and to the sacrotuberous and sacrospinous ligaments. Dorsal spinal rami continued their course laterally, sandwiched between superficial and deep portions of sacroiliac ligaments, piercing the origin of the glutaeus maximus muscle. Histological examination of dissected nerves demonstrated numerous thick myelinated, besides thin myelinated and unmyelinated nerve fibers compatible with a broad repertoire of sensory receptors including encapsulated mechanoreceptors. Histological and immunocytochemical studies on fetal iliosacral joints showed neurofilament positive nerve fibers only in dorsal portions. This innervation pattern may provide explanations for various patterns of pseudoradicular and referred pain in affections of the sacroiliac joint. PMID- 7793156 TI - [Experimental therapy of rheumatoid arthritis with cytokine antagonists]. AB - Although the etiology of rheumatoid arthritis is still unknown, our knowledge of pathophysiologic mechanisms in this disease has markedly increased. Especially the immunological characterization of cells involved in the inflammatory process and their secretory products (cytokines) allowed new experimental therapeutic approaches. Apparently, the cytokines TNF alpha, IL-1, and IL-6, predominantly produced by accessory cells, play an important role in the actual articular and extraarticular inflammation. Therefore, several pilot studies employed various methods to inhibit the effects of these proinflammatory cytokines. This paper provides an overview about initial results of these studies and an outlook with regard to future developments. PMID- 7793159 TI - [Osteopoikilosis--skin and joint manifestations]. AB - Osteopoikilosis (Osteopathia condensans disseminata) is a rare and usually asymptomatic sclerosing bone dysplasia of unknown origin. Familial clustering suggests a dominant inheritance. The observation of a 47-year-old woman lead to differential diagnostic considerations in view of the literature on about 350 cases. For 2 years the patient has been complaining about pain and stiffness of both hands with swelling of the fingers. Additionally, she remarked about bilateral paresthesias corresponding to the sensory innervation of the median nerve. Clinical examination revealed a sensory carpal tunnel syndrome and mild synovitis of the proximal interphalangeal joints with skin induration and limited flexion of the fingers. In addition, some finger and toe nails showed pitting and most fingers had scar-like linear skin alterations. Radiologic findings showed symmetric, well-defined, homogeneous sclerosing areas in spongy bone. The combination of symmetrical sclerosing bone densities, hereditary character, and associated skin and joint manifestations suggests the existence of a general connective tissue disease. PMID- 7793160 TI - [Modern pathogenetically-oriented therapeutic methods for chronic polyarthritis- New World symphony or only an intermezzo?]. PMID- 7793162 TI - [Women live longer]. PMID- 7793161 TI - [Use of cyclosporin A in chronic polyarthritis and other rheumatic diseases]. AB - Cyclosporin A (CyA), a well-established drug in human transplantation for more than 10 years, has been used as an experimental treatment in autoimmune diseases increasingly since 1985. Its efficacy in rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis has been demonstrated in numerous placebo controlled studies. In RA is seems to be equal to azathioprine and D penicillamine. CyA may also be of considerable benefit in other systemic diseases like polymyositis and primary biliary cirrhosis. The risk of side-effects, mainly nephrotoxicity has led to dosage guidelines, including a starting dose between 2.5 and 3.5 mg/kg/day and an upper dose limit of 5 mg/kg as well as dose reduction if serum creatinine is persistently raised by more than 30% of pre treatment values. In the future, CyA may be an ideal partner for drug combinations because of its well-defined mechanism of action (inhibition of lymphokine-, especially interleukin-2-production) and possibly the low-dose sufficient for efficacy in combination. Studies relating to this are on-going. PMID- 7793163 TI - [Hormone substitution in climacteric. Position of the German Menopause Society]. PMID- 7793164 TI - [The age limit in surgical geriatric gynecology]. AB - From 1970 to 1989, 2880 gynecologic surgeries were performed on women aged 80 years and over in Berlin (West). During the period of observation, the operations increased continuously in number. There were 418 in 1970 to 1974; 542 in 1975 to 1979; 777 in 1980 to 1984, and 1143 procedures in 1985 to 1989. This rise can be seen in all groups of diseases. 151 postoperative deaths were reported (5.2%). However, this figure represents an incorrect "hospital-mortality". The number of postoperative deaths decreased despite the increase in surgical procedures: 44 women in 1970 to 1974 (10.5%); 36 women in 1975 to 1979 (6.6%); 44 women in 1980 to 1984 (5.7%); 27 women in 1985 to 1989 (2.4%). This demonstrates that advanced age is no contraindication to an otherwise indicated gynecologic surgery. Our findings support the clinical use of an age limit of 80 years for the examination of problems of "gynecologic surgery in the geriatric patient". This age limit serves for the general work-up of a quantitatively representative material. PMID- 7793165 TI - [Biochemical prognostic factors of ovarian carcinoma]. AB - In therapy decision and monitoring of ovarian cancer clinicians use clinical and histomorphological criteria. Thus, intensive research in tumor biology of ovarian cancer leads to the development of biochemical parameters and a deeper understanding of proliferation and metastasis in-vitro testing of anticancer drugs is one way to achieve a dynamic model to tumor growth. The expression of the erb B oncogene family, especially erb-B-2, is an important finding for the estimation of the potential of an ovary tumor to grow at metastatic sites. The erb B oncogenes encode membrane-growth-factor-receptors functioning in signal transduction for cell growth stimulation. In several studies disease-free survival of advanced ovarian carcinoma was significantly related to the extent of erb-B-2 amplification and/or over-expression. High erb-B-2 expression in the tumor at time of primary treatment indicated a positive second-look-laparotomy. New experimental approaches for alternative therapies use erb-B-2 as the target for interference of tumor cell proliferation. PMID- 7793166 TI - [Lymphohistiocytic infiltration of endometrial adenocarcinoma]. AB - Mononuclear cells adjacent to endometrial adenocarcinoma were evaluated in 8 biopsies by the immunoperoxidase technique. Between benign and malignant tissue a remarkable infiltration of CD45+, CD3+, CD4+, CD8+, and CD14+ cells could be observed. B cells (CD19) and NK cells (CD57) were rare. Tumor-infiltrating lymphocytes were only sparsely distributed. The findings suggest a cellular, yet ineffective, immune reaction of the host against the tumor at the borderline between benign and malignant tissue. PMID- 7793167 TI - [The prognostic value of cathepsin D concentration in cytosol of primary breast carcinoma]. AB - The concentration of total cathepsin D in tumor cytosol was measured in 300 patients with primary breast cancer treated at the Women's University Hospital in Wurzburg between 10/86 and 9/92. Patients were followed for a median of 28 months. The level of cathepsin D was correlated with estrogen receptor status and tumor size but seemed to be independent of progesterone receptor status, histological grading, patient's age, axillary lymph node involvement and primary distant metastases. Overall survival, disease-free survival and metastases-free survival did not differ between patients with cathepsin D-levels above the median value of 47 pmol/mg of protein and patients with cathepsin D-concentration below 47 pmol/mg. Patients with node-negative disease and low cathepsin D-levels (< or = 47 pmol/mg) had a longer disease-free survival than those with cathepsin D concentration > 47 pmol/mg (p < 0.05). Our findings could not confirm cathepsin D as a useful additional prognostic marker in all breast cancer patients. In the low-risk collective the measurement of total cathepsin D may be significant by isolating subgroups with a poorer prognosis who might benefit from adjuvant therapy. PMID- 7793168 TI - [Norplant and its side effects]. AB - Norplant is a subcutaneous contraceptive with levonorgestrel. From March to October 1993. Norplant was implanted in 58 women and its side effects were observed for a period of six months. No pregnancy occurred during the study period. Almost all the women experienced irregular menstruations or amenorrhea. The most frequent side effect was weight gain in 21 women (36.2%) followed by headache (13.7%), hair loss (8.6%) and emotional changes (8.6%). However, they were usually mild and 86.2% of the women showed complete satisfaction at the end of study. Norplant was removed in 6 women for its side effects. Younger women appeared to tolerated better than older women. There was a significant relationship between the frequency of side effects with Norplant and those with previous use of birth control pills. PMID- 7793169 TI - [Comparison of dinoprostone gel and gemeprost suppositories for induction of abortion in the second and third trimester]. AB - The results of the cervical priming with a Dinoprost-containing gel and a Gemeprost-containing vaginal suppository were compared in 68 patients, who required termination of pregnancy beyond 14 weeks because of a severe maternal disease or a fetal abnormality. The priming consisted of either an intracervical application of Dinoprost (500 micrograms) in a tylose-gel in 6-8 hour intervals or a retrocervical application of Gemeprost (1 mg) as a vaginal suppository in 12 hour intervals. Although no significant parameter variances were found in the selected patient groups, abortion was induced in 75% of cases within 24 hours, in 89% within 36 hours using Gemeprost. Mean induction time for Gemeprost was 19.5 hours. Using Dinoprost only 19% of patients had an abortion within 24 hours (44% within 36 hours, respectively), mean induction time was significantly longer (38.8 hours, p < 0.005). These differences remained unchanged, when patients who had a prior caesarean section were not evaluated. Using Gemeprost the additional systemic administration of Sulprost was necessary in 21% of cases, using Dinoprost, in 50% of cases. Severe complications did not occur and minor side effects such as nausea or vomiting were observed in single cases. These results demonstrate that Gemeprost can be used in cervical priming even after 14 weeks of pregnancy and that the longer application interval of 12 hours results in a reduction of side effects without a decrease in efficacy. PMID- 7793170 TI - [Determination of postpartum fructosamine for assessment of gestational diabetes- a suitable method?]. AB - Postpartal screening of undetected gestational diabetes has proven to be difficult. Rapid decrease in diabetogenic hormones and normalisation of the former delayed insulin-response make it difficult to detect disturbed glucose tolerance in the puerperium. Therefore, glycolysated serum proteins offer the opportunity for retrospective diagnosis. They allow an evaluation of the patient's carbohydrate metabolism, retrospectively over several weeks. In this context, we were most interested in the significance of fructosamine. In a prospective study covering 12 months, 123 patients with several risk factors for gestational diabetes underwent a 100 g glucose tolerance test in the puerperium. Furthermore, we measured fructosamine and glycolysated hemoglobin. A carbohydrate intolerance could be detected by the oral glucose tolerance test in 22.7%. In 12.2% of the cases, glycolysated hemoglobin was found to be higher than 5.5%. Fructosamine levels were normal for all patients, with a mean value of 1.84 mmol/l. Even though fructosamine concentration was significantly higher (p < 0.05) in patients with a pathologic glucose tolerance, our study showed the oral glucose tolerance test to be better to detect unknown gestational diabetes than measurement of serum fructosamine. PMID- 7793171 TI - [Sactosalpinx after previous hysterectomy--removal using surgical laparoscopy]. AB - Six consecutive patients with sactosalpinx after preceding hysterectomy were treated by laparoscopic surgery and the outcome was analysed. Irrespective of extensive intraabdominal adhesions the operation could be completed by laparoscopy and the sactosalpinx was successfully removed in all cases. No complications were observed. Operative laparoscopy may be an adequate procedure to remove a sactosalpinx after antecedent hysterectomy. PMID- 7793172 TI - [Hematometra after hysteroscopic endometrium ablation--a case report]. AB - 13 months after a hysteroscopic endometrial ablation a haematometra was diagnosed in a 44 year-old women as a source of recurrent pelvic pain. The cause of the haematometra was a complete obliteration of the ostium cervicae internum. This long-term complication of the endometrial ablation shows that all patients should have a regular clinical and sonographical follow up after endometrial ablation. PMID- 7793173 TI - Evaluation of a companion animal program on a continuing care psychiatric unit. PMID- 7793174 TI - The golden years? Myths and realities. PMID- 7793175 TI - Sexuality in the elderly: what is the health professional's role? PMID- 7793176 TI - Is hearing screening needed for all admissions to a stroke rehabilitation unit? PMID- 7793177 TI - Butyrylcholinesterase variants and the new methods of molecular biology. PMID- 7793178 TI - Identification of human plasma cholinesterase variants using molecular biological techniques. AB - Genetic variation is one of several factors determining the level and quality of plasma cholinesterase activity (butyrylcholinesterase, BChE). The many genetic variants known today, and the resulting large number of genotypes and phenotypes, have complicated the problem of identifying individual BChE genotypes and phenotypes on the basis of enzymatic analyses alone. Modern molecular biological techniques have, however, permitted the development of diagnostic tests which allow BChE variants to be identified at the DNA level. Today, at least 20 genetic variants have been identified in this way. This review is an introduction to the principles of molecular biology used to identify the variants forms of the BCHE gene. PMID- 7793179 TI - Plasma cholinesterase and abnormal reaction to succinylcholine: twenty years' experience with the Danish Cholinesterase Research Unit. AB - For more than 20 years, the Danish Cholinesterase Research Unit (DCRU) has collected information about patients showing an abnormal response to succinylcholine. The purpose of this study was, on the basis of the 20 years' experiences with the Unit, to evaluate our clinical findings in patients referred because of prolonged response following succinylcholine. Also, we wanted to evaluate the results of our prospective controlled studies of the effect of succinylcholine in patients with normal and abnormal plasma cholinesterase genotypes. An explanation for the apparent abnormal response to succinylcholine was found in 61.1% of the 1,247 patients referred to the Unit. Of the 1,247 patients, 28.5% were genotypically normal and 46.5% had an abnormal genotype. In the remaining 24.9% of the patients, the genotype could not be established. The time to sufficient recovery of neuromuscular function following succinylcholine 1.0-1.5 mg kg-1 was 15-30 min in patients heterozygous for one abnormal gene, 35 45 min in patients heterozygous for two abnormal genes and 90-180 min in patients homozygous for the atypical gene. Patients with two newly discovered genotypes (AK (5 patients) and AH (1 patient) showed slightly prolonged (20 min) and markedly prolonged (90 min) duration of action of succinylcholine, respectively. Our results indicate that it is a problem for many anaesthetists to correctly diagnose a prolonged response to succinylcholine. We therefore urge the anaesthetist always to use a peripheral nerve stimulator when faced with a case of apparent abnormal response to succinylcholine. PMID- 7793180 TI - Identification of human plasma cholinesterase variants in 6,688 individuals using biochemical analysis. AB - In 1973, a Cholinesterase Research Unit was established in Denmark (DCRU). The primary aim was to provide a central service for determining genotypes and activity of plasma cholinesterase (BChE) in patients showing abnormal response after succinylcholine. The purpose of the present study was, on the basis of 20 years experience with this Unit, to establish accurate reference intervals for BChE activity and inhibition values for the different genotypes of BChE. Also we wanted to evaluate the influence of age and sex on the BChE activity in genotypically normal patients. Plasma cholinesterase activity was measured using benzoylcholine as substrate. The genetic variations of the enzyme were identified using differential inhibitors, i.e.: Dibucaine, Sodium Fluoride, Succinylcholine, Urea and Ro-2-0683. We investigated 6,688 patients. The reference values for the 13 genotypes represented agree with previous findings. In genotypically normal patients, no age or sex differences were found in BChE activity in children below the age of 10 years. From the age of 10 years the activity decreased significantly in both males and females, the activity in females being significantly lower than in males. In females the activity was lowest in the age group 30-40 years, returning to prepuberty level at about 60 years of age. In males the activity decreased slightly up to 50-60 years of age. Hereafter the activity was stable or tended to increase slightly. Most genotypes could be recognized using the results of the different inhibition studies. We found the inhibitors Dibucaine, Sodium fluoride, Urea and Ro-2-0683 most helpful, whereas succinylcholine was of less value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793182 TI - Topical ketamine inhibits albumin extravasation in chemical peritonitis in rats. AB - BACKGROUND: As ketamine has local anaesthetic actions and local anaesthetics are known to have anti-inflammatory effects, ketamine could be expected to be an anti inflammatory agent. Here we sought to determine whether ketamine is indeed anti inflammatory in chemical peritonitis induced by HCl in rats. METHODS: Peritonitis was elicited by applying 0.02 M HCl on the surface of the cecum or appendix and quantified by measuring the extravasation of intravenously injected Evan's Blue bound to albumin extracted from those tissues. Three experimental sets were performed. In the first set, four groups of 10 rats each received: 1%, 2%, and 4% ketamine and 1% lidocaine. In the same animal, before induction of peritonitis one area was topically pre-treated with 0.9% saline (control site) and another area was topically pre-treated with 1%, 2% or 4% ketamine or 1% lidocaine (experimental site). In the second set, two groups of 10 rats each received: 2% ketamine or 1% lidocaine. Ten min after the induction of peritonitis, the control site was topically treated with 0.9% saline, while the experimental site was treated with 2% ketamine or 1% lidocaine. In the third set 20 rats, divided into two groups, were pre-treated either with 2% S(+)ketamine or 2% R(-)ketamine before the induction of peritonitis instead of the previously employed racemic version of the drug. RESULTS: Treatment of the cecum or appendix areas with ketamine or lidocaine before the induction of peritonitis decreased the extravasation of Evan's Blue-albumin from 5.7 +/- 0.7 micrograms/100 mg tissue to 4.5 +/- 0.8, N.S. with 1% ketamine; from 5.9 +/- 0.8 to 4.1 +/- 0.7, P < 0.01 with 2% ketamine; from 4.8 +/- 0.7 to 3.5 +/- 0.6, P < 0.05 with 4% ketamine and from 5.9 +/- 0.6 to 3.6 +/- 0.8, P < 0.01 with 1% lidocaine. Treatment of the areas of peritonitis with 2% ketamine or 1% lidocaine decreased the extravasation of Evan's Blue-albumin from 5.6 +/- 0.5 micrograms/100 mg tissue to 4.4 +/- 0.6, P < 0.05 and from 6.0 +/- 0.8 to 5.0 +/- 0.7, P < 0.01. Administration of the isomer S(+)ketamine to colonic areas before the induction of peritonitis reduced the extravasation of Evan's Blue-albumin from 6.5 +/- 0.7 micrograms/100 mg tissue to 4.1 +/- 0.6, P < 0.01; while the isomer R(-)ketamine was inactive. CONCLUSIONS: These results indicate that topically applied ketamine inhibited the development of chemical peritonitis. This action of racemic ketamine was due to the isomer S(+)ketamine. PMID- 7793184 TI - Comparison of the recovery characteristics of midazolam, alone or antagonised with flumazenil, and thiopental in ASA III-IV patients. AB - Sixty non-premedicated male patients, physically ASA III-IV, 50-80 years of age, undergoing translumbar aorthography, were randomly allocated into three groups. Group A received midazolam (0.13 mg.kg-1), group B received thiopental (4 mg.kg 1), and group C midazolam (0.13 mg.kg-1) combined with flumazenil (6 micrograms.kg-1) at the end of the operation. Three minutes before the anaesthesia began, fentanyl (1.5 micrograms.kg-1) was administered to all the patients. An evaluation was made of the time they took to open their eyes spontaneously, of time-space orientation, comprehension-collaboration, hypnosedation, psychomotor performance and memory. In groups "C" and "B" spontaneous opening of the eyes took place before that of group "A". The recovery of orientation, comprehension and hypnosedation was fastest with thiopental, next with midazolam combined with flumazenil, and later with midazolam. Psychomotor performance in Trieger test was impaired for a shorter period with thiopental than in the other two groups. Recovery in group "C" was incomplete within the time, with the result that resedation was detected in 20% of the subjects. PMID- 7793183 TI - How are haemodynamic and metabolic responses to haemorrhage influenced by segmental thoracic and thoracolumbar epidural analgesia? An experimental study in dogs. AB - To determine the effects of the spread of sympathetic blockade administered prior to haemorrhage on haemodynamic and metabolic responses to haemorrhage, we compared these responses among dogs treated by segmental thoracic epidural analgesia, thoracolumbar epidural analgesia and general anaesthesia. Group 1 of six dogs received 0.2% halothane plus epidural analgesia ranging from C4 to T5, group 2 of seven 0.2% halothane plus epidural analgesia ranging from C5 to L7, and group 3 of eight 0.9% (1 MAC) halothane anaesthesia. A volume of 35 ml.kg-1 was bled over 30 min. The haemodynamic, metabolic and catecholamine variables were measured repeatedly at 30-min intervals for 2.5 h. The mean arterial pressure decreased significantly in all groups immediately after haemorrhage. It recovered to 80-90 mmHg at 2-2.5 h in groups 1 and 3 but remained at 20-30 mmHg in group 2. The cardiac output decreased significantly in all groups. The systemic vascular resistance increased significantly in group 1 but decreased significantly in group 2. In group 3 it decreased significantly but soon recovered. Arterial pH and base excess decreased significantly in all groups immediately after haemorrhage. After that, base excess recovered slowly in groups 1 and 3 but decreased further in group 2. The plasma epinephrine concentration increased immediately after haemorrhage and then decreased slowly in groups 1 and 3. In group 2 it remained unchanged at the lower level. The decreases in mean arterial pressure, systemic vascular resistance and base excess were significantly larger in group 2 than in groups 1 and 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793181 TI - Interstitial fluid accumulation does not influence oxygen uptake in the rabbit small intestine. AB - Crystalloid resuscitation increases interstitial fluid volume. Intestinal ischemia and impaired barrier function may contribute to the precipitation of multiple organ failure. Accordingly, the intestine was chosen as target organ to test whether interstitial oedema impairs oxygen extraction by the tissue. The portal vein in anaesthetized rabbits was partially obstructed for 30 min along with an intravenous infusion of 0.9% saline 60-90 ml kg-1 (oedema group, n = 7). Total water content of the small intestine increased from 3.4 ml g-1 dry weight in control (n = 8) to 3.9 ml g-1 in the oedema group (P = 0.049). Small intestinal O2 uptake was calculated from the arteriovenous O2 content and electromagnetic flow measurements in the superior mesenteric artery. Mesenteric flow was reduced stepwise by a snare occluder around the artery. Intestinal oxygenation was monitored indirectly as well, by means of mesenteric venous lactate, arterial base excess and by mucosal pH (pHi) assessed tonometrically. The oxygen extraction ratios were similar in the oedema and control group at similar oxygen supplies. After a 45 min flow reduction to 15% of baseline mesenteric venous lactate and pHi did not differ between the groups. pHi averaged 7.31 and fell to 6.74. Below an intestinal O2 uptake of 2.5 ml min-1, pHi correlated somewhat better with O2 uptake (r = 0.66) than did arterial base excess (r = 0.50). The results indicate that acute elevation of extracellular volume to the extent in the present study, does not impede oxygen uptake in the gut. PMID- 7793185 TI - Intramuscular ketorolac following total hip replacement with spinal anaesthesia and intrathecal morphine. AB - We have studied the analgesic and morphine sparing effect of ketorolac tromethamine in 60 patients after total hip replacement under spinal anesthesia. In this double blind study 30 patients received ketorolac 30 mg IM 6 hourly postoperatively and the control group received saline. Analgesia was assessed by visual analogue pain scores (VAS) and morphine consumption by patient controlled analgesia (PCA). There was a significantly (P < 0.02) lower morphine consumption in the ketorolac group (7.1 +/- 8.6 mg; Mean +/- s.d.) when compared to the saline group (14.2 +/- 13.6 mg). Although there was a trend for lower VAS on the first postoperative night this was only significant at 10 hours postoperatively and the next morning at 08:00 hr. The incidence of side effects (emetic sequelae, pruritus and headache) were similar in both groups. It is concluded that ketorolac reduces the consumption of additional morphine in conjunction with intrathecal morphine but had no effects on the side effects. PMID- 7793187 TI - Effects of hypothermia on the elimination of ethanol, diazepam and oxazepam in rat liver slice incubations. AB - The elimination of ethanol, diazepam and oxazepam which are metabolised by different enzymes, has been studied for 30, 60, 90 and 120 min at 37, 27, 17 and 7 degrees C in rat liver slice incubations. Ethanol elimination followed zero order kinetics at all temperatures, while the benzodiazepines consistently displayed first-order kinetics. No sign of phase transition was observed in the respective Arrhenius-plots. Ethanol elimination was more temperature dependent than the elimination of diazepam, while the elimination of oxazepam was little influenced by temperature. This is shown by the temperature ratios (Q10) and energies of activation (Ea) of 1.76, 1.56, 1.24 and 40.5, 31.9, 15.2 for ethanol, diazepam and oxazepam, respectively. This means that ethanol, diazepam and oxazepam elimination was reduced by 25, 22 and 14%, respectively, for each 10 degrees C of temperature reduction, which is considerably lower than the commonly observed 50% reduction of enzyme activity. We conclude that observations made for one drug on temperature dependent elimination may not apply to other drugs. PMID- 7793186 TI - Effect of intraperitoneal bupivacaine on pain after laparoscopic cholecystectomy. AB - The effect of intraperitoneal bupivacaine on postoperative pain was studied in 60 ASA 1-2 patients undergoing elective laparoscopic cholecystectomy. The patients were randomly selected (20 patients in each group) to receive in double-blind fashion 100 mo of either plain 0.15% bupivacaine (150 mg.100 ml-1) or the same solution with adrenaline (1.5 micrograms ml-1), or the same volume of saline into the right subdiaphragmatic space at the end of surgery. The patients were kept in the Trendelenburg's position for 20 min after the instillation. Venous blood samples for the determination of bupivacaine plasma concentrations were drawn up to 180 min. Plasma bupivacaine concentrations peaked at 30 min (highest individual value 2.6 micrograms ml-1) after instillation. Bupivacaine concentrations were significantly lower in the bupivacaine-adrenaline group. During the follow-up no difference between the groups occurred as to the time to first demand of analgesia, severity of postoperative pain, amount of consumed analgesics during 7 days, and length of hospitalization. In all groups, 30-45% of the patients complained of right shoulder pain. After the first 24 hours, pain at rest and during moving was reported as mild and was managed with oral ketoprofen. It is concluded that postsurgical intraperitoneal instillation of 150 mg bupivacaine in 100 ml of saline had no effect on pain after laparoscopic cholecystectomy. PMID- 7793188 TI - Intravenous propofol vs thiamylal-isoflurane for caesarean section, comparative maternal and neonatal effects. AB - Several studies on propofol (Diprivan) for induction of anaesthesia during caesarean section have demonstrated its safety, however, it safety during maintenance of anaesthesia is not yet fully evaluated. The present study was undertaken to compare the maternal and neonatal effects of propofol or isoflurane in 74 term parturients undergoing primary or repeat caesarean section. Patients were randomly assigned to two groups, propofol group (n = 37) received propofol 1.5-2.5 mg.kg-1 for induction followed by a continuous infusion of propofol of 0.05-0.2 mg.kg-1.min-1. The isoflurane group (n = 37) received thiamylal 3-4mg.kg 1 for induction followed by isoflurane 0.25-0.75% for maintenance. All patients had rapid sequence induction using succinylcholine and endotracheal intubation, 50% N2O and O2 were used in all patients until delivery. After delivery N2O concentration was increased to 67% and intravenous butorphanol (Stadol) was given as needed. Patients in the propofol group had less hypertension after intubation (P < 0.05) and this was also of shorter duration compared to patients in the isoflurane group (5 min vs 10 min respectively). Maternal blood loss as well as intraoperative awareness and recovery time did not differ significantly between the two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the neurological and adaptive capacity scores (NACS) was equally good in both groups. It is concluded that propofol used for induction and maintenance of anaesthesia is a safe alternative to thiamylal/isoflurane for patients undergoing caesarean section and is associated with less hypertensive response during laryngoscopy and intubation. PMID- 7793189 TI - Prilocaine reduces injection pain caused by propofol. AB - Propofol, which is commonly used for outpatient anaesthesia, may evoke pain during infusion. Forty-eight patients (ASA-I-II) undergoing elective uterine dilatation and curettage received randomly in a standardised fashion: A: Propofol mixed with prilocaine; B: Propofol and lidocaine; C: Propofol with prilocaine+lidocaine (equal amounts) or D: Propofol and saline. The final ratio of propofol:local anaesthetic/saline was 9:1 in all mixtures. Pain on injection was significantly decreased in the three groups receiving propofol and local anaesthetic(s) compared to the one given propofol and saline. Propofol is required in greater amounts when mixed with lidocaine than when mixed with saline. A binding between the algesic part of the propofol molecule and the local anaesthetic agent may explain these findings. Another twenty-two comparable patients were given 30 mg of ketorolac or an equal volume of saline intramuscularly 45-60 minutes prior to propofol. Ketorolac given before propofol did not reduce pain on injection. This indicates that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism does not play a major role in the reduction of this pain. PMID- 7793190 TI - Eye symptoms, visual evoked potentials and EEG during intravenous infusion of glycine. AB - Disturbance of vision is a complication that may occur from absorption of the glycine solution used to irrigate the bladder during transurethral operations. We examined for a possible dose-response relationship between glycine dose, eye symptoms and neurophysiological changes after repeated intermittent intravenous infusions of 4.4 g of glycine for up to 22 g over 1 h in 10 male volunteers. The serum glycine concentration increased from 230 +/- 75 to 5,232 +/- 1,088 mumol/l (mean +/- s.d.) during the infusions. We found an increase in diastolic arterial pressure but no significant changes in systolic pressure, heart rate or mental status. Five of the volunteers developed blurring of vision which lasted for 10 30 min. The visual evoked potentials (VEP) of these subjects showed an increase of the P100 and N70 latencies which started after no more than 4.4 g of glycine had been administered. The amplitude of the VEP was preserved and the main frequency of the EEG did not change, indicating that VEP changes were not due to cortical dysfunction. There was no dose-response relationship between glycine infusion and eye symptoms but a sub-group of volunteers responded with both visual disturbances and VEP changes. PMID- 7793191 TI - Potency and maintenance requirement of atracurium and vecuronium given alone or together. AB - A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N2O-O2-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose response curves for these muscle relaxants. ED95-values for atracurium and vecuronium were 260 +/- 9 and 59 +/- 3 micrograms.kg-1, respectively (mean +/- s.e. mean). Requirements of atracurium and vecuronium to maintain an 85-95% neuromuscular blockade were 301 and 83 micrograms kg-1 h-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED95 of a cAV was 94 +/- 7 micrograms.kg-1 of atracurium together with 21 +/- 2 micrograms.kg-1 of vecuronium, or 72 +/- 6% of one ED95 dose of a parent agent. Potentiation was significant (P = 0.0001). A maintenance requirement of a cAV was 120 micrograms kg-1 h-1 of atracurium together with 27 micrograms kg-1 h-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%. PMID- 7793192 TI - Rectal versus intramuscular morphine-scopolamine as premedication in children. AB - Intramuscular morphine-scopolamine for premedication was compared with a hydrogel of the same drugs for rectal administration in 205 healthy children scheduled for minor ENT surgery. The intramuscular dose was 0.15 +/- 0.006 mg x kg-1 compared to 0.25 +/- 0.015 mg x kg-1 rectally. Reaction at administration and anaesthetic induction, incidence of intraoperative airway difficulties, Spo2, ECG changes, postoperative pain and incidence of nausea were recorded. The administration for the rectal hydrogel group worked better and resulted in less postoperative nausea and slightly more postoperative pain. The children's behaviour at anaesthesia induction and the frequency of perioperative complications were similar in both groups. We conclude that for minor ENT surgery on children, premedication with rectal hydrogel of morphine-scopolamine is a good alternative to intramuscular morphine-scopolamine. PMID- 7793193 TI - Comparison of cardiac output measurement techniques: thermodilution, Doppler, CO2 rebreathing and the direct Fick method. AB - Simultaneously measured cardiac output obtained by thermodilution (TD), transcutaneous suprasternal ultrasonic Doppler (DOP), CO2-rebreathing (CR) and the direct Fick method (FI) were compared in eleven healthy subjects in a supine position (SU), a sitting position (SI), and during sitting exercise at a workload of 50 W (EX). The agreements between the techniques, two by two, were expressed as the bias calculated as the averaged differences between the techniques. Precision was expressed as the standard deviation of the bias. The overall agreement (bias +/- precision) between TD, DOP and CR respectively and FI were 2.3 +/- 1.6, -0.1 +/- 1.4, and -0.2 +/- 1.1 l/min. TD overestimated cardiac output consistently in SU, SI and EX. DOP was in-accurate during EX and agreed well with FI in SU and SI. CR agreed closely with FI in SI and EX, but values were underestimated in SU. The overall agreement between DOP and CR, respectively, and TD were 2.5 +/- 2.2 and 2.6 +/- 1.6 l/min. The overall agreement between DOP and CR was 0.1 +/- 1.6 l/min. In conclusion, TD overestimated cardiac output compared to the other techniques and the poor agreement has to be taken into consideration especially in measures of low values. The precision of DOP and CR against FI seems to be within clinically acceptable limits, and these methods may provide interchangeable alternatives to the invasive Fick method. PMID- 7793194 TI - Ethanol monitoring of irrigating fluid absorption in transcervical resection of the endometrium. AB - BACKGROUND: We evaluated the precision in using ethanol to indicate and quantify absorption of irrigating fluid during transcervical resection of the endometrium. METHODS: The ethanol concentration in the expired breath, the serum sodium level, the blood loss and the volumetric fluid balance were measured over 10-min periods during 62 operations. A solution containing glycine 1.5% and ethanol 1% was used to irrigate the uterus. RESULTS: Most principles previously outlined for ethanol monitoring in transurethral prostatic surgery could also be applied in endometrial resection. In the 21 patients who showed the intravascular pattern of ethanol changes, the breath alcohol measurement corrected for absorption time predicted the volume of irrigant absorbed (up to 2,531 ml) with a standard error of 230 ml at the end of any 10-min period of absorption. Repeated measurement of serum sodium indicated intravascular fluid absorption with practically the same precision as the breath test. Extravascular absorption was found in 14 patients. In these operations, the volume of irrigant absorbed (up to 1,767 ml) could be predicted with a standard error of 92 ml from the ethanol concentration at the plateau level attained after absorption had occurred. CONCLUSION: Ethanol monitoring is precise enough to allow monitoring of irrigating fluid absorption in endometrial resection. PMID- 7793195 TI - Desflurane analgesia for vaginal delivery. AB - The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn. Desflurane, with the characteristics of rapid onset and minimal metabolism, may provide better analgesia and safety for labour pain control. Eighty healthy parturients were randomly assigned to receive either desflurane 1.0-4.5% and oxygen (n = 40) or nitrous oxide 30-60% in oxygen (n = 40). Analgesia was assessed using a score from 0 (no relief) to 4+ (excellent analgesia), amnesia for the delivery, blood loss were recorded. Neonates were evaluated by Apgar scores and neurologic and adaptive capacity scores (NACS). Data were analyzed for statistical significance using Student's t-test or Chi-square when appropriate. Analgesia scores were similar for both groups with more amnesia in desflurane group (23% vs 0% P < 0.05). Blood loss did not differ significantly, 364 ml for the desflurane group and 335 ml for the nitrous oxide group. There were no significant differences for neonatal Apgar score at 1 min or at 5 min or the NACS at 2 hr or 24 hr between the two groups. We conclude that desflurane in subanaesthetic doses is safe and effective inhalation agent for normal delivery but might be associated with amnesia. PMID- 7793197 TI - Prolonged interference of blue dye "patent blue" with pulse oximetry readings. AB - Several blue dyes were reported to interfere with the accurate determination of oxygen saturation by pulse oximetry. However, in previous reports the interferences were observed only for a short duration. We have experienced a case in which the interference by a blue dye, "patent blue" continued for a long time. It was suggested that the blue dye, when it was injected intra-arterially and in an anaemic patient, interfered with the pulse oximetry measurement to a greater extent. PMID- 7793196 TI - Death associated with anaesthesia and surgery in Finland in 1986 compared to 1975. AB - Mortality associated with anaesthesia and surgery in Finland in 1986 was studied using a retrospective method and was compared with the results of a similar study performed in 1975. The total number of procedures was 325,585. 570 patients fulfilled one of the three criteria: 1. The patient died within three days of a procedure needing anaesthesia. 2. The patient died more than three days after a procedure needing anesthesia, but had suffered a cardiac arrest or been resuscitated, or there was a surgical or an anaesthesiological complication contributing to the death. 3. The patient suffered a major handicapping neurological (or other) deficit, which was associated with anaesthesia, or there was a surgical or an anaesthesiological complication possibly contributing to the death or handicap (no patients). The number of consultant anaesthesiologists had more than doubled since 1975. At the same time there was also a significant increase in recovery room and intensive care facilities. Surgery was the main contributing factor in the death of 22 (frequency 0.68/10,000 procedures), and anaesthesia in the death of five (frequency 0.15/10,000 procedures) patients. The role of surgery had decreased to about one third and the role of anaesthesia to less than one tenth as the main cause of death associated with anaesthesia and surgery compared to the year 1975. 95.3% of all the patients died mainly because of co-existing medical or surgical disease. PMID- 7793198 TI - Blood-stained pleural effusion complicating interpleural analgesia. AB - A case of blood-stained pleural effusion complicating interpleural analgesia for a difficult nephrectomy is reported. We describe our technique of placement of the interpleural catheter. Interpleural infusion of 0.25% bupivacaine at 7 mls/h provided excellent postoperative analgesia. However, a left pleural effusion was demonstrated from chest X-ray films taken from the third day post-operatively. Persistent low grade fever and a large pleural effusion necessitated drainage which resulted in improvement in symptoms. Possible aetiologies of the effusion are discussed, although the exact cause was uncertain. Observation for a developing pleural effusion and other complications should form part of the postoperative observation and if one does develop, the necessary measures can be taken. PMID- 7793199 TI - Intraoperative anaphylaxis caused by a hydatid cyst. AB - The incidence of the hydatid disease is still high in some regions of the Mediterranean. A serious, but rare, peroperative complication is IgE-mediated anaphylaxis, as a result of passing of the highly antigenic hydatid cyst content into the bloodstream. We present here a case of anaphylactic reaction in a patient who underwent surgical treatment of hydatid cyst. PMID- 7793200 TI - Needle fixation with combined spinal-epidural anaesthesia. PMID- 7793201 TI - Pulse oximetry--clinical implications and recent technical developments. AB - The pulse oximeter has been shown to be a reliable monitor of arterial oxygen saturation and has therefore been recommended as mandatory monitoring for patients during anaesthesia and intensive care. In 1989 two review articles on pulse oximetry were published (1, 2) and two years ago Severinghaus and Kelleher summarized the literature between 1989 and October 1991 (3). Our aim is to focus the discussion on technical aspects and applications of pulse oximetry with special attention centered on recent developments. This review is consequently an update on pulse oximetry since the end of 1991, and the first on technically based publications in the two last decades. PMID- 7793202 TI - Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions. AB - We conducted a survey of the incidence of Postoperative Residual Curarisation (PORC) in two groups of patients following the use of atracurium or vecuronium. In the first group (B) the neuromuscular blocking drugs were administered by bolus dosing, and in the second group (I) by continuous fusion. On arrival in the recovery room, neuromuscular function was assessed both by compound evoked electromyogram (EMG) in a train of four pattern and also clinically, by the ability to sustain a headlift for > 5 seconds, and to cough. Results were obtained from 150 patients (100 in group B and 50 in group I). The incidence of PORC, as defined by a train of four ratio of < 0.7, on arrival in the recovery room was 12% in group B, and 24% in group I. Clinical criteria of adequate neuromuscular reversal revealed different results, with the majority of patients being unable to perform either clinical test on arrival in recovery. Those patients in whom a peripheral nerve stimulator was used intra-operatively did not have a reduced incidence of PORC. We have demonstrated that PORC is still a common occurrence even with intermediate duration of action neuromuscular blocking drugs. PMID- 7793203 TI - Epidural anaesthesia blocks changes in peripheral lymphocytes subpopulation during gastrectomy for stomach cancer. AB - To examine the effects of surgery and anaesthesia on cell-mediated and humoral immunity, we investigated changes in subpopulations of peripheral T cells and B cells during gastrectomy. Twenty-one patients with gastric cancers who underwent total or subtotal gastrectomy were randomly assigned to receive thiopental/N2O general anaesthesia supplemented with either epidural (epidural group, n = 12) or enflurane(enflurane group, n = 9). The changes in peripheral lymphocyte subpopulations were detected and quantified using single and double label analysis of monoclonal antibodies against lymphocyte membrane surface markers (Leu series). Subpopulations were measured before induction, and 1 and 2 hours after skin incision. In the enflurane group, B cells (Leu12+), total T cells (Leu4+), inducer T cells (CD4+, Leu8+) and the CD4/CD8 ratio decreased and suppressor T cells (CD8+, Leu15+) increased significantly after skin incision. Whereas, the epidural group showed no change in the number of B cells and each T cell subpopulation during the study. These data suggest that epidural anaesthesia blocks the effect of stress induced by major surgery on fluctuation of peripheral lymphocyte subpopulations which may be associated with suppression of immunity. PMID- 7793204 TI - Lack of effect of flumazenil on the reversal of propofol anaesthesia. AB - Propofol, like the benzodiazepines, activates the GABAA receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 micrograms fentanyl, propofol 2 mg.kg-1 was injected for induction and followed by infusion at the rate of 15 mg.kg-1.hr-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 micrograms.kg-1 (Group B) randomly. Recovery time in Group A was 15.2 +/- 5.1 min and Group B 15.8 +/- 4.8 min. Propofol concentrations at the end of infusion were 4.17 +/- 1.33 micrograms.ml-1 (Group A) and 4.03 +/- 1.45 micrograms.ml-1 (Group B); these then declined to 1.22 +/- 0.17 micrograms.ml-1 (Group A) and 1.18 +/- 0.15 micrograms.ml-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 micrograms.kg-1 does not influence recovery from propofol anaesthesia. PMID- 7793205 TI - Lung function after open versus laparoscopic cholecystectomy. AB - Postoperative lung function and gas exchange were studied in 36 patients after cholecystectomy. Twenty-four of the patients underwent laparoscopic cholecystectomy while the remaining twelve were operated with open technique. Before surgery all patients had normal ventilatory volumes (forced vital capacity, FVC and forced expired volume in 1 s, FEV1) and normal gas exchange. Two hours postoperatively FVC was reduced to 64 +/- 16% (P < 0.05) of the preoperative level in the laparoscopic group and to 45 +/- 23% (P < 0.05) after open cholecystectomy. On the first postoperative day FVC was virtually normal in the laparoscopic patients (77 +/- 17% of preoperative level, NS), whereas the open surgery patients still had a decreased FVC (56 +/- 13% of preoperative, P < 0.05). FEV1 in the postoperative period followed the same course as FVC. Gas exchange was significantly impaired in the early postoperative period in all patients but no difference between the two groups was found. Two hours postoperatively PaO2 was reduced to 85% (P < 0.05) of preoperative value and PaCO2 had increased by 0.5 kPa (P < 0.05). The alveolo-arterial oxygen tension difference (PA-aO2) had increased by approximately 45% to a mean of 3.7 kPa (P < 0.05). On the first postoperative day gas exchange was still significantly impaired in the open surgery patients. Atelectasis detected by computed X-ray tomography of the lungs were found in both groups. However, the amount of atelectasis tended to be smaller in the laparoscopic group than in the open surgery patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793206 TI - Clinical application of differential ventilation with selective positive end expiratory pressure in adult respiratory distress syndrome. AB - Differential ventilation in the lateral position with positive end-expiratory pressure (PEEP) selectively applied to the dependent lung (DVSP) has been shown to reduce venous admixture and improve oxygenation without compromising cardiac output in short term studies of patients with acute respiratory failure. We have applied this ventilation technique as a long-term treatment in severe adult respiratory distress syndrome (ARDS) in an open clinical trial. Eleven patients with ARDS of varying aetiology were treated with DVSP for a total of 34 days. Median duration of conventional ventilatory therapy before start of DVSP was 5 days (1 to 18 days), inspiratory oxygen fraction (FIO2) was 0.61 +/- 0.16 (mean +/- s.d.), resulting in a mean arterial oxygen tension (PaO2) of 7.1 +/- 2.1 kPa (PaO2/FIO2 = 11 +/- 4 kPa). A gradual improvement in gas exchange was seen during the first 24 h of DVSP such that PaO2 increased to 8.4 +/- 1.4 with a decreased FIO2 (0.52 +/- 0.14) resulting in an increased PaO2/FIO2 (16 +/- 5 kPa). Five out of the eleven patients survived. No major complication was noted using DVSP as a method. We found a steady improvement in gas exchange over the first 24 hours in most patients. However, mortality rate was no lower than expected. Drawbacks with DVSP were increased demand on staff and difficulties with adequate endo-bronchial suctioning. PMID- 7793207 TI - Protective effects of halothane but not isoflurane against global ischaemic injury in the isolated working rat heart. AB - The effects of equi-anaesthetic concentrations of halothane (HAL) and isoflurane (ISO) on myocardial performance, perfusion, oxygenation and lactate release were studied before, during and after a low-flow, global ischaemic insult in isolated, paced rat left heart preparations. An antegrade perfusion technique was used, where left atrial pressure (LAP) and mean aortic pressure (MAP) could be altered independently of each other. Aortic flow, coronary flow (CF) and PO2 in venous coronary effluent were continuously recorded and stroke volume, myocardial oxygen consumption (MVO2) and myocardial oxygen extraction as well as lactate release were calculated. The hearts were exposed for at least ten minutes to the perfusate without (control, n = 10) or with HAL (n = 10) or ISO (n = 10) at a MAP of 80 mmHg (10.4 kPa) and a LAP of 7.5 mmHg (1.0 kPa). After baseline measurements, MAP was reduced to 25 mmHg (3,2 kPa) for a total of nine minutes. Thereafter MAP was increased to 80 mmHg (10.4 kPa) for another nine minute period. During the whole experimental procedure, LAP was maintained at 7.5 mmHg (1.0 kPa) and heart rate at 325 beats per minute. In the pre-ischaemic control period, MVO2 was lower with HAL compared to ISO (P < 0.05) and control (P < 0.05). Stroke volume was also lower with HAL compared to control (P < 0.05). During hypoperfusion, lactate release was twice as high in the control group (P < 0.01) and with ISO (P < 0.01) compared to HAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793208 TI - Attenuation of hyperoxic lung injury in rabbits with superoxide dismutase: effects on inflammatory mediators. AB - BACKGROUND: Superoxide dismutase (SOD) has been shown to attenuate hyperoxic lung injury. This effect is thought to be exhibited by scavenging superoxide released from neutrophils and other aerobic cells. The aim of the current study was to investigate the effect of pre-treatment with SOD on the chemical mediators in hyperoxic lung injury. METHODS: Thirty male anesthetized rabbits were allocated to receive one of three treatments (n = 10 for each group): ventilated with 100% oxygen for 36 h with or without recombinant human SOD (rhSOD) treatment, and ventilated with air for 36 h without rhSOD. In the rhSOD-treated group, a single intravenous dose of rhSOD 10,000 U kg BW-1 was administered immediately after the start of exposure to 100% oxygen and thereafter infused at a rate of 340,000 U kg BW-1 day-1 for 36 h until the animals were sacrificed. The lungs of all rabbits were ventilated with 100% oxygen or air. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure to 100% oxygen, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolite concentrations in BALF were measured and analyzed. The lung wet-to-dry (W/D) weight ratio and albumin concentrations in BALF were determined as indices of pulmonary oedema. RESULTS: Exposure to the high concentration of oxygen for 36 h caused no significant changes in haemodynamics but decreased compliance and increased A-aDo2. In the rhSOD-treated group, the decrease in compliance was not observed. At the end of the 36 hr-exposure period, however, hyperoxia significantly increased the lung W/D weight ratio, influx of neutrophils into the lung, BALF concentrations of C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, thromboxane B2, and albumin. Pre-treatment with rhSOD attenuated these increases. Exposure to 100% oxygen caused extensive morphologic lung damage (alveolar haemorrhage and hyaline membrane formation), which was lessened by rhSOD. CONCLUSION: These results indicate that intravenous rhSOD prevented hyperoxic lung injury (decreases in PaO2 and compliance, increased pulmonary vascular permeability, histopathological damage) in rabbits. This prophylactic effect of rhSOD amy be due, in part, to decreased chemical mediators such as activated complements, cytokines, and arachidonic acid metabolites. PMID- 7793209 TI - Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. AB - The postoperative analgesic effect of ibuprofen was compared with a combination of ibuprofen and codeine versus placebo. The study was prospective, randomized, double blind with 123 consecutive hip arthroplasty operations. All the patients received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3-4 ml. Postoperatively, when the spinal anaesthesia started to wear off, the patients were randomly assigned to one of three groups; the ibuprofen group (n = 48) received 800 mg of ibuprofen orally. The ibuprofen/codeine group (IC, n = 48) received 800 mg of ibuprofen combined with 60 mg of codeine. The placebo group (P, n = 25), received oral placebo medication. The patients were observed for the need of additional opioid (e.g. ketobemidone), pain score (verbal and VAS), bleeding and side effects for five hours. The patients in the placebo group (P) had significantly higher pain scores (P < 0.05) compared with the two other groups after 2 and 4 hours, with no significant differences after 1, 3 and 5 hours. The P group also received 45% more opioids (P < 0.001) compared with the two other groups during the same period. No significant differences in bleeding or side-effects were observed between the groups. There were no significant differences between the ibuprofen group and the ibuprofen/codeine group. We conclude that a prophylactic dose of 800 mg ibuprofen orally has an opioid sparing effect with a tendency of less pain experience during the first hours after hip arthroplasty. PMID- 7793210 TI - Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans. AB - Endogenous nitric oxide (NO) is thought to regulate many biological functions, including pulmonary circulation and bronchomotion, and it has been found in exhaled air. Our aim was to study the excretion of NO in different parts of the respiratory system. Exhaled concentrations of NO were measured by chemiluminescence in chronic tracheostomy outpatients (group 1), in patients admitted for minor abdominal surgery (group 2), and in patients with acute respiratory failure (ARF) during mechanical ventilation (group 3). In awake volunteers (group 4), 0.57 L/min gas was aspirated through the nasal cavity into the chemiluminescence device. In group 1 (tracheostomy, n = 5) we detected 16 +/- 2 (mean +/- s.e. mean) parts per billion (ppb) NO when exhaling through the mouth, and a lower (P < 0.05) value of 4.6 +/- 0.8 ppb NO when exhaling through the tracheostomy. Before anaesthesia, group 2 (n = 11) exhibited 18 +/- 2.4 ppb NO in orally exhaled gas, increasing considerably during exhalation through the nose. Upon endotracheal intubation exhaled NO concentration dropped to 1.3 +/- 0.2 ppb (P < 0.05). In group 3 (ARF, n = 7) tracheal NO concentrations were 0.8 +/- 0.2 ppb. In group 4 (volunteers, n = 6) 394 +/- 23 ppb NO was recorded in air from the nasal cavity. In both healthy subjects and patients with respiratory failure a significant NO excretion occurs in the lower airways and lungs. The upper airways, especially the nose, contribute the largest amount of NO (> 90%) to exhaled air. The physiological implications of an upper airway source of NO remain to be defined. PMID- 7793211 TI - Implicit processing and therapeutic suggestion during balanced anaesthesia. AB - The effect of therapeutic suggestion--implicit processing during balanced anaesthesia was studied in 70 female patients scheduled for elective breast surgery. The patients were randomly allocated to listen to a message with reassuring information focused on minimising postoperative nausea and vomiting, or just a blank tape during surgery. Occurrence of nausea and vomiting was studied during the postoperative period. No patient recalled any explicit memories during the peroperative period. No major differences were observed in the number of patients who experienced nausea or vomiting during the 24 hour observation period. The patients exposed to positive suggestion did, however, have a lower frequency of recall for nausea and vomiting compared to those just listening to the blank tape. We did not observe any major effect of peroperative suggestion for postoperative nausea and vomiting. However, we cannot rule out some implicit processing during balanced anaesthesia. PMID- 7793212 TI - Autogenous production of hydroxyl radicals from thiopental. AB - It is generally believed that barbiturates can protect neural tissues from the damage induced by cerebral hypoxia. One of the mechanisms for protecting neurons is through the inhibition of lipid peroxidation (LPO). We therefore examined LPO in rat brain, liver and kidney by measuring the accumulation of thiobarbituric acid-reactive substances (TBAR) after thiopental administration under 21% O2. We also designed an in vitro study to gain insight into free radical generation leading to the formation of LPO from thiopental by electron spin resonance (ESR). An accumulation of TBAR in the rat liver was observed after the administration of a large dose of thiopental (70 mg/kg intraperitoneally). However, no change in LPO in the brain and kidney was observed. In the in vitro study, thiopental could scavenge superoxide (O2-.) radicals, while it spontaneously generated hydroxyl radicals (.OH) in solution. We conclude that thiopental can scavenge O2-., while producing .OH, subsequently resulting in membrane lipid peroxidation under physiologic O2 conditions. This formation of .OH may damage cell membrane lipids. PMID- 7793213 TI - Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene. AB - Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 mumol.l-1 ryanodine. After pretreatment with 1 mumol.l-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8 +/- 1.8 min) and MHN (46.0 +/- 4.2 min) muscle specimens than after ryanodine alone (MHS 4.8 +/- 0.7 min. (MHN 13.7 +/- 0.9 min). They were no longer observed in either group after pretreatment with 5 mumol.l-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependently, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site. PMID- 7793214 TI - Effects of hypotensive treatment with alpha 2-agonist and beta 1-antagonist on cerebral haemodynamics in severely head injured patients. AB - Therapy of post-traumatic brain oedema often includes preservation of high arterial blood pressure to avoid secondary ischaemic injuries to the brain. This practice can be questioned since high arterial blood pressure may aggravate brain oedema through raised hydrostatic capillary pressure, causing fluid filtration across the damaged blood-brain barrier. This latter view is in agreement with our clinical experience and therefore hypotensive therapy with an alpha 2-adrenergic agonist (clonidine) and a beta 1-adrenergic antagonist (metoprolol) has become part of our treatment protocol for severely head injured patients to decrease the post-traumatic brain oedema. The present study is an attempt to analyse whether there are any direct local cerebrovascular effects of the hypotensive agents used, which also might influence intracranial pressure. Severely head injured patients were investigated. Heart rate, mean arterial blood pressure, intracranial pressure, cerebral blood flow and arteriovenous difference in oxygen content were measured before and after a bolus dose of clonidine (six patients) and metoprolol (nine patients). Clonidine decreased mean arterial blood pressure and cerebrovascular resistance without affecting other parameters measured. Metoprolol decreased heart rate and mean arterial pressure, but had no effect on the cerebrovascular parameters. The results show that clonidine and metoprolol have no, or only minor, direct influence on local cerebral haemodynamics in severely brain injured patients. This implies that if there is an intracranial pressure reducing effect of these drugs, as suggested, this must be due to other mechanisms, namely a reduction in capillary hydrostatic pressure secondary to decreased arterial blood pressure and heart rate. PMID- 7793215 TI - Diabetic autonomic neuropathy and the haemodynamic actions of vecuronium and pancuronium during vitrectomy. AB - In order to clarify whether autonomic neuropathy modifies the haemodynamic effects of alfentanil, vecuronium and pancuronium, twenty-seven patients with diabetes mellitus were studied at thiopentone induction, and during nitrous oxide anaesthesia for ophthalmic vitreous surgery. Heart rate was lower in the diabetic patients receiving vecuronium compared with those receiving pancuronium, but no difference was seen in arterial pressure. During and after anaesthesia induction, the profiles of heart rate and arterial pressure resembled those found in healthy controls. Even in patients with advanced autonomic neuropathy, anaesthetics may exert their inherent vagotonic or sympathicotonic actions. PMID- 7793216 TI - Comparison of induction time and characteristics between sevoflurane and sevoflurane/nitrous oxide. AB - A previous investigation using nitrous oxide with 5% enflurane (3.8 MAC) for single breath induction produced a stage of excitement which may be related to the difference in blood/gas coefficient solubility of these agents. The closer blood/gas solubility coefficient of sevoflurane and nitrous oxide may eliminate this phenomenon. We therefore evaluated 40 volunteers in a randomized study using 7.5% sevoflurane (3.7 MAC) in oxygen (n = 21) or sevoflurane with nitrous oxide (n = 19) using a single breath induction technique. Sevoflurane in nitrous oxide and oxygen reduced induction time by 15% compared to sevoflurane in oxygen alone (41 +/- 16 and 48 +/- 16 sec (s.d.), respectively). This was, however, not statistically significant. There were scarcely induction-related complications, such as coughing, laryngospasm, breath-holding, movements of a limb and excessive salivation, in either group. Thus, the addition of nitrous oxide neither increased the number of complications, nor the speed of induction. PMID- 7793218 TI - Long-term local corticosteroid application does not influence nerve transmission or structure. AB - The long-term effects of a locally applied depot form of a corticosteroid on the electrical properties and structure of nerves were investigated in an animal experimental model. The conduction in electrically stimulated A-fibres of the plantar nerve was monitored by a bipolar volley recording of the sciatic nerve whereas the conduction in C-fibres of the plantar nerve was measured through a C fibre evoked segmental flexion reflex in the anaesthetized rat. Droplets of either methylprednisolone acetate or vehicle were placed under direct observation on the plantar nerve. Saline was used as a control on the contralateral side. One to two weeks after the application both the A-fibre volley of the sciatic nerve and the C-fibre evoked reflex discharge of flexor motoneurons were recorded. No difference was found between the nerves treated with corticosteroid, constituent vehicle or saline. Light and electron microscopic analysis of the nerves showed no changes in the nerve fibres or in the intraneural connective tissue in either the corticosteroid treated or the control nerves. It is concluded that locally applied corticosteroids in limited amounts have no long-term effects on the electrical and structural properties of peripheral nerves. PMID- 7793217 TI - Oral premedication one hour before minor gynaecological surgery--does it have any effect? A comparison between ketobemidone, lorazepam, propranolol and placebo. AB - The purpose of the present study was to compare the effects of oral premedication with ketobemidone 5 mg, lorazepam 1 mg, propranolol 40 mg or placebo, given about an hour prior to anaesthesia, in a prospective randomized double-blind fashion. One hundred and twenty ASA I female patients scheduled for elective laparoscopy were randomly prescribed one of the study drugs. Patient evaluation of anxiety, nurse evaluation of premedication, induction and postoperative course were studied. Ninety-three of the 120 patients (78%) experienced no change or a decrease in anxiety, regardless of type of active drug or placebo administered. Eighty-eight of the patients (73%) were considered adequately premedicated by the nurse observer, with no differences between the groups. Pre induction pulse rate, blood pressure and amount of induction agent needed was also similar between the four groups of patients. No major differences could be seen during the postoperative course. We found no major effects of any of the active drugs studied compared to placebo. Routine use of small doses of oral premedication one hour before elective surgery among low anxiety patients could probably be omitted. PMID- 7793219 TI - Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation. AB - The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction. PMID- 7793220 TI - Recovery from sevoflurane and isoflurane anaesthesia after outpatient gynaecological laparoscopy. AB - As the low blood solubility (blood gas partition coefficient 0.69) of sevoflurane suggests a rapid emergence from anaesthesia, recovery from sevoflurane anaesthesia was compared to isoflurane in outpatient gynaecological laparoscopy. Fifty ASA I or II, consenting women participated in a randomised, controlled and single blind study. The patients received, after induction of anaesthesia with propofol, either sevoflurane or isoflurane, both with 67% nitrous oxide in oxygen, for maintenance of anaesthesia. The study drug was administered at 1 MAC (end tidal concentration 0.6% for sevoflurane and 0.5% for isoflurane) but adjusted in 0.5 MAC steps, if clinically indicated. Before the end of surgery the end tidal concentration of the study drug was reduced to 0.5 MAC. Recovery assessments were made from the time anaesthetic gases were discontinued. The subjects were able to open eyes in 2.3 (0.8-7.0) min and 4.1 (2.0-6.8) min, orientate in 2.8 (1.0-6.8) min and 4.7 (2.2-8.3) min and follow orders in 2.6 (0.7-6.8) min and 4.3 (1.2-7.3) min, in the sevoflurane and isoflurane groups, respectively (P < 0.05) [median (range)]. Walking was achieved in 72 (24-464) min and 66 (35-134) min, tolerance of oral fluids in 37 (15-88) min and 35 (45-161) min and voiding in 262 (96-459) min and 217 (52-591) min in the sevoflurane and isoflurane groups, respectively (NS). Overall home readiness was achieved in 281 (96-708) min after sevoflurane group and 242 (96-591) min after isoflurane (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793221 TI - Anesthetic modulation of the cardiovascular response to microlaryngoscopy. A comparison of propofol and methohexital with special reference to leg blood flow, catecholamines and recovery. AB - The modulating effects of propofol versus methohexital on the cardiovascular response to microlaryngoscopy were studied in 35 patients divided into four equal groups (one patient participated twice). Heart rate (HR), mean arterial blood pressure (MAP, cardiac output (CO; impedance cardiography), leg blood flow (LBF; occlusion plethysmography) and concentrations of arterial catecholamines were measured. After administration of atropine and fentanyl (2 micrograms.kg-1), anesthesia was induced by either an injection of propofol (2.0 mg.kg-1) followed by a low (6 mg.kg-1.h-1; n = 9) or a high (12 mg.kg-1.h-1; n = 9) dose propofol infusion or an injection of methohexital (1.5 mg.kg-1) followed by a low (5 mg.kg 1.h-1; n = 9) or a high (10 mg.kg-1.h-1; n = 9) dose methohexital infusion. The low methohexital infusion dose was insufficient to control MAP, which increased 41% during microlaryngoscopy compared to the awake state. The HR increased in all groups but the increase was most prominent in the low dose methohexital group. There were no statistically significant changes in CO in any group, whereas LBF increased consistently in all groups except in patients anesthetized with the low dose of methohexital. The increases of LBF in the propofol groups were intermediate and not dose dependent. The methohexital low dose group showed increases in norepinephrine levels compared to awake values and in epinephrine levels compared to the other groups. Propofol seems to differ from methohexital in modulation of peripheral vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793222 TI - Perioperative autotransfusion and functional coagulation analysis in total hip replacement. AB - Functional coagulation analyses like Sonoclot and thromboelastography have not been evaluated during perioperative autotransfusion. We have prospectively studied three different transfusion regimes in 45 patients undergoing total hip arthroplasty. Blood losses were replaced either with heterologous erythrocyte concentrate (group I), intra- and postoperative autotransfusion of blood salvaged with cellsaver technique (group II) or predonated autologous erythrocyte concentrates together with salvaged blood (group III). Routine and functional coagulation analyses with a Sonoclot were performed preoperatively, 6 hours postoperatively (6 h), day 1-5 and 10. An early postoperative hypo- and late postoperative hypercoagulative phase could be detected with Sonoclot signs of platelet function and fibrin deposition in all groups. Sonoclot coagulation analyses better correlated to both blood loss and dextran dosage than APTT and platelet count in the routine coagulation analyses. Functional coagulation analysis has a potential use in individualizing plasmasubstitution and thromboprophylaxis regimes during autotransfusion in THR. PMID- 7793224 TI - ECG T-wave amplitude changes during thiopentone induction with or without alfentanil. AB - The T-wave amplitude of ECG is thought to reflect the sympathetic tone of the heart but anaesthesia studies on this topic are rare. Haemodynamic and ECG T-wave amplitude changes were studied during induction of anaesthesia in 24 ASA I-II patients. Twelve patients were given alfentanil 30 micrograms kg-1 at induction while physiologic saline was given to the rest (control). Thiopentone was then administered at the rate of 5 mg s-1 until eyelash reflex disappeared. Vecuronium 0.1 mg kg-1 was given thereafter. No anticholinergics were used. The lungs were ventilated with 40% oxygen in air. Haemodynamic parameters and T-wave amplitude were measured before induction, before intubation, 30 s, 3 min and 5 min after intubation. A significantly higher amount of thiopentone was needed to abolish the eyelash reflex in the control group than in the alfentanil group (P < 0.001). There were no changes in heart rate (HR) in the alfentanil group during the trial. Systolic and diastolic arterial pressures (SAP and DAP) were continuously below the preinduction levels in the alfentanil group. After baseline HR, SAP and DAP were significantly higher in the control group than in the alfentanil group at each data point. T-wave amplitude flattened significantly (P < 0.001) after intubation in the control group while no significant changes were seen in the alfentanil group. T-wave flattening correlated to the increases in HR (P < 0.01) and SAP (P < 0.01). Three control patients with flattened T-wave had a transient bigeminia period after intubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793223 TI - Erythrocyte counts in the cerebrospinal fluid associated with continuous spinal anaesthesia. AB - Continuous spinal anaesthesia technique can be associated with peridural haemorrhage due to blood vessel damage caused by the needle or the catheter. We studied whether thrombosis prophylaxis or anticoagulation medications increase the risk of subarachnoid haemorrhage when continuous spinal anaesthesia is used. Twenty arthroplasty patients received low-molecular-weight heparin preoperatively and twenty-two vascular surgery patients received heparin (100 IU kg-1) peroperatively; eight of the latter patients were on regular preoperative antiplatelet medication. Twenty-four prostate surgery patients, not exposed to heparin or other drugs affecting coagulation, served as controls. A 22-gauge spinal catheter was used and bupivacaine was injected through the catheter. Within the following 24 hours, 4-5 cerebrospinal fluid samples were collected for erythrocyte counts. In the arthroplasty and the vascular group there were five patients each and in the control group seven patients with more than 100 x 10(6) l-1 erythrocytes in at least one of the samples. The highest erythrocyte count was 23900 x 10(6) l-1 in a control patient. The 24-hour sample was blood-tinged (erythrocytes > 1000 x 10(6) l-1) in two patients in the arthroplasty group, in one patient in the vascular group and in four patients in the control group. In spite of the haemorrhages detected in this study, no related neurological symptoms or other serious consequences were observed. The risk of subarachnoid haemorrhage was not increased by drugs affecting coagulation. PMID- 7793226 TI - Early detection of CO2 pneumothorax with continuous spirometry during laparoscopic fundoplication. AB - In two patients, operated on because of gastroesophageal reflux, carbon dioxide pneumothorax developed during laparoscopic Nissen fundoplication. In both instances, decrease of lung compliance and a change of pressure-volume loop configuration, computed and illustrated with on-line spirometry, led quickly to diagnosis of this complication. We conclude that continuous spirometry is valuable as an early indicator of intraoperative pneumothorax. PMID- 7793225 TI - Train-of-four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans. AB - Previous studies have suggested that the increased duration of action of long acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N2O/fentanyl anaesthesia. Study subjects were paralyzed with either pancuronium (N = 8), pipecuronium (N = 8), or the longer-acting relaxant, doxacurium (N = 8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED95 dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% of baseline response to the first supramaximal twitch (T1) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded. Spontaneous recovery to 25% of the baseline T1 response occurred at 52 +/- 14 min (mean +/- SD) following administration of either pancuronium and pipecuronium, and 85 +/- 33 min following doxacurium (P < 0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-treated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 +/- 14% and 61 +/- 16%, respectively) than with either pancuronium (75 +/- 6% and 75 +/- 10%) or pipecuronium (76 +/- 9% for both).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793227 TI - The laryngeal mask simplifies airway management during percutaneous dilational tracheostomy. AB - The Laryngeal Mask Airway (LMA) is used for many procedures which previously required endotracheal intubation. Percutaneous Dilational Tracheostomy (PCT) facilitates the bedside insertion of a tracheostomy tube in the Intensive Care Unit. Most patients requiring this procedure are intubated with a conventional endotracheal tube. Insertion of a LMA has advantages over tracheal intubation for PCT mainly because the artificial airway lies remote from the operating field. Three cases are reported to illustrate these advantages. PMID- 7793228 TI - Long-term survival and predictors of mortality in Alzheimer's disease and multi infarct dementia. AB - Long-term survival was examined for 218 patients with Alzheimer's disease (AD) and 115 patients with multi-infarct dementia (MID). The 14-year survival rate for AD was 2.4% versus an expected rate of 16.6%, and for MID 1.7% versus 13.3% expected. MID showed a more malignant natural course than AD. Men carried a less favourable survival prognosis than women, both in AD and MID: the relative risk of dying for women was half that for men in both diseases. In MID, advanced disability indicated a relative risk of dying over twice as high. In both diseases the risk of death was substantially higher in the event of occurrence of primitive reflexes. PMID- 7793229 TI - Cu, Zn superoxide dismutase in patients with dementia of the Alzheimer type. AB - Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT. PMID- 7793230 TI - Rising mortality from Parkinson's disease in Japan, 1950-1992. AB - The death rate from Parkinson's disease (PD) were analyzed using Japanese vital statistics for 1950-1992. The age-adjusted PD death rate increased statistically significantly with the years between 1950 and 1992 for both sexes. However, decline in the PD death rate were observed among the population under 65 years old, while striking increases were seen among those over 70 years old. The changing patterns in the PD death rate might be explicable by a constantly improving ascertainment of PD, a true rise in the incidence of PD, particularly among the elderly, and a constantly increasing number of elderly people. There were remarkable differences in the PD death rates among the four marital categories in each sex. The mean age at death in PD increased from about 60 years in 1950 to 77 years in 1992 for both sexes. PMID- 7793231 TI - Early selegiline therapy reduces levodopa dose requirement in Parkinson's disease. AB - In an earlier report of our placebo-controlled selegiline trial on de novo parkinsonian patients, we have shown that the need to start additional levodopa therapy is significantly postponed by using selegiline monotherapy. Now we report the two-year interim results of the double-blind continuation of the trial in 44 patients after the introduction of levodopa to the earlier therapy with placebo or selegiline (21 and 23 patients, respectively). The clinical disability was assessed by three rating scales. The daily dose of levodopa needed to maintain an optimal condition had to be increased progressively up to a 52% higher level in the placebo group than in the selegiline group (543 +/- 150 and 358 +/- 117 mg, respectively, p < 0.001). The number of daily doses of levodopa was also statistically significantly higher in the placebo group during the 24 months' observation period (p < 0.01). The ratio of levodopa doses that was expected to stay the same contrarily significantly increased suggesting that selegiline would, besides having the levodopa potentiating effect, also have a beneficial influence on the progression of the basic cerebral dopamine deficiency. The combination of selegiline and levodopa was well tolerated, and the adverse event profiles did not differ from each other. In conclusion, early selegiline therapy allows a significant saving in the subsequent levodopa dosage. This saving seems to become even stronger along with the treatment time. PMID- 7793232 TI - Hereditary ataxias and paraplegias in Valle d'Aosta, Italy: a study of prevalence and disability. AB - INTRODUCTION: a study was conducted in the Valle d'Aosta Region, Italy, (115270 inhabitants) to determine the prevalence of hereditary ataxias (HA) and hereditary spastic paraplegias (HSP), and the degree of disability they cause. METHODS: we identified all patients with suspected HA or HSP referred from 1981 to 1991 to in- and out-patient departments, EEG, EMG, and CT-scan services, and centres for the handicapped. Harding's criteria were followed for diagnosis and classification. RESULTS: at the prevalence day, 17 patients were alive, with a prevalence ratio of 14.8/100,000 population. There were 2 cases of Friedreich's ataxia (FA), 1 of early onset cerebellar ataxia with retained tendon reflexes (EOCA), 1 of autosomal dominant cerebellar ataxia (ADCA), 8 of sporadic idiopathic late onset cerebellar ataxias, and 5 of HSP. CONCLUSIONS: epidemiological studies on HA and HSP show highly variable prevalence ratios, which could be due in part to the inclusion of sporadic cases. FA, EOCA and ADCA have similar prevalence ratios in most studies. PMID- 7793233 TI - Correlation between magnetic resonance imaging and clinical parameters in multiple sclerosis. AB - In this study, the course of 60 consecutive multiple sclerosis patients (relapsing-remitting (RR), relapsing-progressive (RP), primary-progressive (PP)) was compared with the number and mean size of the lesions as well as the total load of the lesions as shown on magnetic resonance imaging (MRI). Significant differences were found between RR and RP patients in total load and number of lesions. Between RR and PP patients statistical significant differences were found in total load, number and size of the lesions when correlated with EDSS. Between RP and PP patients statistical differences were found in total load and size of the lesions on MRI. Patients with a relapsing course of the MS (RR or RP) had a higher total load and size of the lesions than PP patients. The total load, number and size of the lesions corrected for EDSS were also lower compared to relapsing patients. Factor analysis showed a correlation between clinical progression rate and progression rate of MRI abnormalities. No correlation between EDSS and total load of MRI lesions could be found. In conclusion, this study confirms the results of previous studies of differences between MRI scans of patients with a different course of MS. PMID- 7793234 TI - Associated autoimmune diseases in myasthenia gravis. A population-based study. AB - During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe. PMID- 7793235 TI - Familial spasmodic dysphonia with low arylsulphatase A (ASA) level. AB - Two familial cases of late onset spasmodic dysphonia and low Arylsulphatase A (ASA) are reported. In one case spasmodic dysphonia was associated with negative head tremor and orthostatic tremor, both displayed postural tremor of the upper extremities. A familial predisposition for both focal dystonia and metabolic lysosomal impairment is suggested by similar observations. PMID- 7793236 TI - Lamotrigine as an add-on drug in typical absence seizures. AB - INTRODUCTION: Lamotrigine is licensed in many countries for use in patients with partial seizures. Evidence suggests that it may also be effective in generalised epilepsies. MATERIAL & METHODS: We analysed retrospectively our patients with idiopathic generalised epilepsy with refractory absences. RESULTS: Fifteen patients with idiopathic generalised epilepsies were identified who had been treated with lamotrigine for 3 months or more. All patients were also treated with sodium valproate. Fourteen patients had active absences. Nine (64%) had a total or virtual cessation of absences and in a further patient they became milder and less frequent. One patient reported an increase in seizures. The effective dose of lamotrigine was 1.6-3.0 mg/kg/day in children and 25-50 mg/day in adults. Patients who responded did so after the first or second dose. Lamotrigine was well tolerated. CONCLUSION: Low-dose lamotrigine added to sodium valproate appears to be effective in typical absence seizures. A therapeutic interaction of the two drugs seems likely. PMID- 7793237 TI - The prognostic value of the EEG in asphyxiated newborns. AB - Peripartal asphyxia is still one of the most important factors of neonatal morbidity and mortality and accounts for the majority of non-progressive neurological deficits seen in children. A set of evaluations that may consistently predict outcome in this patient population would be valuable. The purpose of the present retrospective study was to investigate the prognostic value of the early neonatal EEG and Sarnat scoring obtained in 23 asphyxiated term newborns. All infants met strict entrance criteria, regarding asphyxia, and received standard treatment. The relationship between the Sarnat scoring, the early EEG findings, and the clinical follow up examination (at 1,5-7 years) were studied using the Pearson Correlation test and multiple regression. Our study clearly demonstrates a strong correlation between the early neonatal EEG and outcome, even regarding the prediction of minor sequelae (r = 0.79, p < 0.0001). The early neonatal EEG is more accurate in predicting the ultimate clinical outcome than the Sarnat scoring. PMID- 7793238 TI - Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment. AB - An increased referral of patients with anticoagulation related haemorrhages necessitated an analysis of causes and outcome of these complications in a patient group that reflected Swedish therapeutic traditions of anticoagulation treatment. Prospectively, all patients from Stockholm evaluated for warfarin related intracranial haemorrhage occurring during 1987 were analysed and their 6 month outcome recorded. Sixty-eight patients were included. The results of intracranial haemorrhagic complications were catastrophic with a 77% mortality rate. Their incidence was much higher than expected. Forty-one patients had non traumatic intracerebral haematomas, 1 had a non-traumatic subarachnoid haemorrhage and 26 had traumatic injuries. In the 42 patients with non-traumatic haemorrhages, the indications for anticoagulation were cerebral ischaemic events in a majority (27/42). The remaining 15 patients had different indications for anticoagulation. They also had an increased frequency of hypertension (p < 0.05). In the 26 patients with traumatic haematomas, only 6/26 patients had previous cerebral ischaemic injuries (p < 0.01). Valvular heart prosthesis was their most common indication (11/26) for anticoagulation. Caution in instituting anticoagulation therapy in patients with hypertension or cerebrovascular disease, which is an important indication for anticoagulation in Sweden, is mandatory. Adherence to strict treatment regimens and their continuous reevaluation may help to avoid complications. The finding of more patients than expected with haemorrhagic complications is not compatible with the risk evaluations used to justify anticoagulation therapy in the patient groups studied. Clinical practice must have changed with time, showing that risk evaluations from controlled trials or retrospectively collected clinical data from selected patients are not necessarily applicable for long-term clinical practice. PMID- 7793240 TI - Decreased plasma alanine and isoleucine in Huntington's disease. AB - Amino acid concentrations in plasma of patients with Huntington's disease (HD) were determined in 16 patients and 21 age- and sex-matched healthy controls. Alanine and isoleucine were significantly decreased in HD plasma whereas arginine, histidine, leucine, lysine, ornithine, proline, serine, threonine, tyrosine, and valine showed no significant changes. Our findings confirm the decreases of alanine and isoleucine that were described in plasma and cerebrospinal fluid by other investigators. A possible defect in cellular uptake or metabolism of neutral amino acids seems to be a consistent feature of HD. PMID- 7793241 TI - Abnormal penetration of haptoglobin through the blood-brain-barrier (BBB) into the cerebro-spinal fluid (CSF) in Alzheimer's disease patients. PMID- 7793239 TI - A follow-up study of neuropsychological functioning in AIDS-patients. Prognostic significance and effect of zidovudine therapy. AB - Thirty-three patients with AIDS were subjected to neuropsychological and immunological testing with semi-annual examinations over a two year period. No patient had signs of opportunistic infections or neoplasms in the CNS. Patients who were neuropsychologically impaired at the time of AIDS diagnosis (n = 12) survived for a significantly shorter period than did the non-impaired subjects (n = 21), and neuropsychological function at first test had a significant predictive value concerning survival time. The poor prognosis associated with impaired neuropsychological status was seen also in patients treated with zidovudine (ZDV). Of the 21 patients who started ZDV treatment shortly after the first neuropsychological examination, 12 were retested. Follow-up data showed that this group of patients had a significant improvement in neuropsychological functioning during the first 6 months. However, a decrease in performance was observed at second follow-up. In the group not treated with ZDV (n = 7), two initially normal patients developed signs of HIV-encephalopathy, while none of the initially normal ZDV-treated patients did so. This might suggest a prophylactic effect of ZDV on development of neuropsychological dysfunction. Changes in neuropsychological test results were correlated with changes in serum concentration of neopterin irrespective of ZDV treatment, suggesting that monocyte/macrophage activation may be involved in the pathogenesis of HIV encephalopathy. PMID- 7793242 TI - Clozapine in the treatment of tremor in Parkinson's disease. PMID- 7793243 TI - [Oncogenes and cancer of the larynx. EGFR, p21 ras and HPV-DNA infections]. AB - The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa specimens was evaluated. Scattered p21 levels, expressed as optical density (O.D), were found in normal mucosa (median = 1.94) and in primary laryngeal tumours (median = 1.74). Higher p21 levels were found in neoplastic tissue than in normal laryngeal tissue (median = 2.54 vs median = 1.94; p = 0.023). The correlation between p21 ras protein and EGFR levels was also investigated. EGFR+ cases do not show any difference in p21 expression with respect to EGFR- cases (median = 1.52 O.D. vs median = 1.84). Our findings suggest that overexpression of p21 is associated with malignant phenotype in laryngeal cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7793244 TI - Analysis of seven pedigrees of childhood Wilson's disease characterized by abdominal symptoms. AB - In a survey of childhood Wilson's disease (WD) characterized by abdominal symptoms, three patients with high levels of immunologically detectable ceruloplasmin (CP) in serum were found. These three cases were compared with typical cases of WD in which serum CP level was low. In order to clarify the cause of WD, serum CP levels were quantified by two methods, an immunological protein assay and an oxidase activity assay. Using the results of these two assays, WD cases were classified into three groups on the basis of CP content; the first group consisted of patients with low enzyme activity and low CP protein content, the second group consisted of patients with low enzyme activity and normal CP protein content, and the third group, those patients with normal enzyme activity and normal CP protein content. No significant difference in symptoms was observed between these three groups. Since relatively high levels of CP were detected in some WD patients, genetic variation in CP in WD patients was examined by restriction enzyme fragment length polymorphism analysis using CP cDNA. However, no large deletion in the CP gene was detected. Using four types of gene probes for chromosome 13 known to be related to WD, the DNA of WD patients was examined in a similar fashion, but no significant difference was observed between the groups. PMID- 7793245 TI - Growth and development of 280 hypothyroidic patients at diagnosis. AB - The growth and development of 280 hypothyroidic patients who were diagnosed from 1979 to 1991, has been evaluated by standardized anthropometric criteria. According to the chronologic age during the diagnosis, the patients were divided into five groups of 0-6, 7-12, 13-24, 25-60 and 61-144 months. In these groups, the rates of the patients' weights and heights which were found below the 5th percentile, were as follows; for height 44%, 69%, 71%, 85%, 80% and for weight 38%, 68%, 70%, 55%, 60% respectively. Height age, weight age, head circumference age, and bone age were found to be significantly lower than chronologic age in all the groups, with the exception of the head circumference age in the 0-6 months group. The bone age was found to be significantly retarded compared to the height age in all the groups. PMID- 7793246 TI - Influence of parental obesity on the physical constitution of preschool children in Japan. AB - The objective of this study was to assess the influence of parental obesity on the physical constitution of preschool children. A total of 3187 children aged between 1-6 years and their parents were studied. A child whose per cent obesity (%OB; per cent overweight for age, height and sex) was greater than 15%, and a parent whose body mass index (BMI; kg/m2) was greater than the 95th percentile were defined to be obese (27.40 and 25.97 for a father and a mother, respectively). We found that the incidence of obesity in children with obese fathers (11.5%) was significantly higher than in those with non-obese fathers (6.2%), and a similar difference was obtained between children with obese mothers (14.5%) and with non-obese mothers (6.2%), respectively. The incidence of obesity in children was 6.0% if both parents were non-obese; this incidence rose to 22.7% if one parent was obese, and to 30.8% if both were obese. The %OB of children was more markedly correlated with the mothers' BMI (r = 0.219) than the fathers' BMI (r = 0.165). The %OB of children correlated significantly with fathers' BMI, but only from the age of 3-6 years, whereas mothers' BMI correlated from the age of 1 6 years. We conclude that parental obesity was of significance in determining the development of juvenile obesity even in the preschool period. PMID- 7793247 TI - Age-related profile of neuroblastoma: a comparison of tumors detected by mass screening with those detected clinically. AB - Infants with neuroblastoma are known to have a favorable prognosis compared to those over 1 year of age. However, there is little biological information about the age-related heterogeneity of neuroblastoma. We evaluated the biological profile comparing cases detected by mass screening with those detected clinically. A total of 238 patients with neuroblastoma were classified into four groups according to their age at diagnosis. Patients in group A were 0-5 months of age (n = 31). Patients in group B were detected clinically and were 6-11 months of age (n = 25). Patients in group C were 6-11 months of age and were detected by mass-screening (n = 97). Patients in group D were more than 12 months of age (n = 85). The age-related heterogeneity was evaluated by Kaplan-Meier survival analysis, several clinical markers (neuron specific enolase, ferritin, vanillylmandelic acid and homovanillic acid) at diagnosis, tumor Ha-ras p21 expression and tumor N-myc amplification. Infant neuroblastoma had unique features in comparison to neuroblastoma diagnosed over 12 months of age. Clinical outcome of the patients in groups A and C was quite favorable. Even patients with stage III or IV disease in group A had a favorable prognosis. However, stage IVs disease in group A was not necessarily associated with a good prognosis and the early death after diagnosis was also characteristic. The biological profile of tumors in group C was similar to that in group A but different from the profile in groups B and D. Tumors in group B had a biological profile intermediate between groups A and D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793248 TI - Opsonic activity in cord blood: comparison between normal and elevated immunoglobulin M infants. AB - In order to clarify the relation between opsonic activity (OA) in newborn infants and their gestational age, we determined OA by Cypiridina luciferin analog dependent chemiluminescence (MCLA-CL). In addition, complement C3 which plays the major role in OA, was determined by the two-dimensional immunodiffusion method. Although OA and C3 in newborn infants increased in proportion to their gestational age, the levels were significantly lower in full-term infants than in adults. In neonates with IgM levels of more than 30 mg/dL at birth, both OA and C3 levels were significantly higher than in normal neonates, yet these levels were significantly lower than in adults. These findings suggest that low opsonin activity is an important factor in neonatal susceptibility to infection. When OA is measured by chemiluminescence, MCLA-CL is the preferred technique to luminol dependent chemiluminescence. PMID- 7793249 TI - Inhaled nitric oxide and extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn. AB - Persistent pulmonary hypertension of the newborn (PPHN) may occasionally require an invasive treatment with extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (NO) has recently been introduced as a selective pulmonary vasodilator for treatment of PPHN. We describe a case of PPHN in which neither inhaled NO nor ECMO was effective in reversing pulmonary hypertension. The clinical course of the patient suggested a potential role of NO inhalation in predicting the outcome of ECMO treatment for PPHN. PMID- 7793250 TI - Nephrocalcinosis in newborn. AB - Nephrocalcinosis is uncommon in childhood, and almost always develops outside the newborn period. Over the last decade, nephrocalcinosis due to multifactorial pathogenesis has increased in very low birthweight infants. In this report a 23 day old full-term baby with nephrocalcinosis secondary to distal renal tubular acidosis is described. PMID- 7793251 TI - Persistent vacuoles in leukocytes: familial Jordans anomaly. AB - Multiple persistent vacuoles were seen in the neutrophils, monocytes and eosinophils of a 9 year old boy and his 10 year old sister. The siblings were both asymptomatic. In the bone marrow, the cytoplasmic vacuoles were also present in the promyelocytes, myelocytes and metamyelocytes, but not in the myeloblasts and they tended to be single and large in immature cells. The cytoplasmic vacuoles did not stain with PAS, Sudan Black or Oil Red O; Sudan III positivity of the vacuoles was found only in a very small number of granulocytes. The vacuoles appeared as round and bright bodies with phase contrast microscopy. By electron microscopy, the vacuoles contained material of low electron density and had no surrounding membrane. Granulocyte functions were unimpaired. Muscle biopsy showed normal morphology. This anomalous vacuolization of the leukocytes is consistent with familial Jordans anomaly. PMID- 7793252 TI - Unique form of rickets with low serum 25-hydroxyvitamin D in two normally nourished children. AB - We present an unusual type of rickets involving two children: a 2 year old boy and a 15 month old boy, who presented with marked bowing of the lower extremities and bulging of costochondral junctions. Both children had normal growth, with their height and body weight greater than the 50th and 97th percentile for age. Roentgenograms of their extremities showed the typical changes of vitamin D refractory rickets. Serum alkaline phosphatase levels were elevated and serum levels of calcium and phosphate were both within the normal range. No primary cause for the rickets, including nutritional deficiencies, was found in the two patients. Characteristic findings were persistently low serum 25-hydroxyvitamin D (25-OH-D) and normal 1,25-dihydroxyvitamin D (1,25-(OH)2-D). Improvements in clinical and X-ray findings were observed after either oral administration of 1 alpha-(OH)-D3 (9-15 micrograms per day) or massive vitamin D2 therapy (600,000 IU single injection). The low serum levels of 25-OH-D did not increase unless massive vitamin D2 therapy was also given. These two cases represent a unique form of rickets that does not meet the criteria for any type of previously known rickets. PMID- 7793254 TI - Hypercalcemia associated with Aeromonas hydrophila gastro-enteritis. AB - We describe a 4 year old girl with acute Aeromonas hydrophila gastro-enteritis who presented with a combination of hypercalcemia, metabolic alkalosis, and renal impairment. Serum parathyroid hormone was not elevated. Both milk-alkali syndrome and intoxication of vitamins A and D were ruled out. The hypercalcemia, metabolic alkalosis, and renal impairment were improved by fluid infusion and intravenous administration of furosemide. Gastro-enteritis also improved with oral administration of the antibiotic norfloxacin. The association of A. hydrophila gastro-enteritis with hypercalcemia has not been described previously. PMID- 7793255 TI - Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency. AB - We report the case of a 3 year old boy who exhibited recurrent serious infections with a transient imbalance of IgG subclass in the second year of life. He suffered from pneumococcal meningitis at 3 months, hepatitis at 9 months, and purulent arthritis at 11 months of age. The second episode of pneumococcal meningitis occurred at 14 months. Serum IgG level was normal for age. Low level of IgG2, undetectable level of IgG4 and negligible level of pneumococcus-specific IgG1-G2 antibodies were found. No other primary immunodeficiency was apparent. Serum IgG2-G4 levels but not pneumococcus-specific IgG1-G2 titers increased by the age of 30 months. At that time, he was inoculated with a polyvalent pneumococcal vaccine along with acellular diphtheria-pertussis-tetanus vaccine. He acquired the immunity against these agents, and had no episodic infections in the following 2 years. This observation stresses the existence of transient IgG subclass deficiency associated with delayed development of the anti polysaccharide antibody response. PMID- 7793256 TI - Transient low level of IgG3 induced by sepsis. AB - Staphylococcus aureus sepsis developed in a 14 year old girl. Immunological evaluation revealed low level of IgG3, although total IgG level was normal. The level of IgG3 increased gradually along with the recovery from sepsis. Immunoglobulin replacement therapy might have been useful in this patient, even though the total immunoglobulin level was within normal limits. PMID- 7793253 TI - A case of distal 9q trisomy syndrome associated with an unusual inheritance of ABO blood type. AB - A male infant with distal 9q trisomy syndrome associated with an unusual inheritance of ABO blood type is reported. His clinical features were concordant with those of distal 9q trisomy syndrome. His karyotype was 46,XY, -10, +der (10) t(9;10) (q22.3;q24.3) confirmed by G-banding and high resolution methods. His father had the balanced translocation t(9;10) (q22.3;924.3). He had a blood type of AB, despite his father's blood type of AB and his mother's blood type of O. The gene of ABO blood type is located at 9q34.1-q34.2. Therefore, he would have received A and B type alleles from his father. 9q trisomy syndrome should be carefully investigated with ABO blood type. PMID- 7793257 TI - Beta-thalassemia with the IVS-I-1 (G-->T) mutation in a Japanese girl. AB - We analyzed the hemoglobins of a Japanese girl with beta-thalassemia and those of her immediate family. DNA sequencing of the cloned beta-globin gene from this patient revealed a point mutation at the IVS-I position 1 (G-->T). This rare point mutation has been found in Asian Indians, but this is the first reported Japanese case. PMID- 7793258 TI - A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection. AB - An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants. PMID- 7793259 TI - Fatal cytomegalovirus myocarditis in a seronegative ALL patient. AB - Fatal cytomegalovirus (CMV) myocarditis occurred in a 2 year old boy with acute lymphoblastic leukemia (ALL) in remission. The patient showed mild hepatic dysfunction and a rapid progress of pancytopenia after complete remission had been achieved. At the fifth week of complete remission, he presented signs of heart failure such as tachycardia, S4 gallop on auscultation and decreased ejection fraction on echocardiography. However, no significant electrocardiographic changes were recognized. In addition to the cardiac dysfunction, the patient presented a marked tachypnea and dyspnea associated with hypoxemia. These were dramatically improved by methylprednisolone pulse therapy (30 mg/kg per day, for 3 days) and CMV high titer immunoglobulin (400 mg/kg per day, for 3 days). On the sixth day after signs of respiratory failure were improved, the patient suddenly presented a paroxysmal atrial tachycardia followed by a fatal ventricular fibrillation. Although we could detect neither a specific IgM antibody, a significant increase of IgG antibody, nor CMV genome by DNA hybridization techniques during the course of the illness, microscopic examination of necropsy specimens of the heart showed a marked disruption and disintegration of muscle bands associated with cytomegalic inclusion bodies. Polymerase chain reaction (PCR) yielded a 305 bp amplification product in the heart and lung tissues, supporting the view that myocarditis was caused by CMV. PMID- 7793260 TI - Interferon-alpha potentiates priming-dependent FMLP-induced neutrophil superoxide generation in a patient with chronic myeloid leukemia. AB - A 13 year old girl diagnosed as having chronic myeloid leukemia (CML) was treated with interferon-alpha (IFN-alpha) alone and 4 months later hematological remission was obtained. In the course of the IFN-alpha treatment there was neither infectious sign nor side effects. In this study we have examined the effect of IFN-alpha on superoxide O2- generation by polymorphonuclear neutrophils (PMN). The PMN of the patient generated less O2- than PMN from normal controls. When patient PMN were cultured in the presence of 1000 U/mL IFN-alpha, enhancement of the formyl-methionyl-leucyl-phenylalanine induced O2- generation following priming with tissue necrosis factor-alpha was observed. Over the course of the IFN-alpha therapy, such O2- generation was gradually restored. It is suggested that CML PMN are in the resting condition in terms of their ability to generate O2- and that IFN-alpha is effective in inducing O2- generation by CML PMN. PMID- 7793261 TI - Occurrence of acute megakaryoblastic leukemia in a patient with idiopathic growth hormone deficiency. AB - We describe a case of a 15 year old boy who developed acute megakaryoblastic leukemia (AMKL) while receiving treatment with human growth hormone (hGH) for idiopathic growth hormone deficiency (GHD). He was diagnosed as having idiopathic GHD and given hGH from December 1991. The examination of his peripheral blood showed mild pancytopenia 2 months before the start of the hGH therapy. Since January 1992, paleness of the skin, general fatigue and fervescence progressed gradually. In February 1992, because of the occurrence of acute leukemia, administration of hGH was discontinued. Judging from the results of surface marker analysis of the blast cells, the patient was diagnosed as having AMKL. He was treated with chemotherapy for acute non-lymphoblastic leukemia from March 1992. A complete remission was obtained after 4 weeks of treatment. The chemotherapy was completed in July 1993. He remains in complete remission 26 months after diagnosis. This case suggests the importance of hematological examination and, when there is any abnormality which is not caused by GHD, such as pancytopenia, more detailed medical examinations (for example bone marrow examination) are necessary. PMID- 7793262 TI - Mononucleosis-like illness in an infant associated with human herpesvirus 6 infection. AB - Illnesses resembling mononucleosis, hematologically characterized by atypical lymphocytosis in the peripheral blood, are caused by other viral infections as well as by a primary Epstein-Barr virus infection. Human herpesvirus 6, a newly isolated member of the herpesvirus group, can also cause a mononucleosis-like illness. Illness associated with human herpesvirus 6 infection mostly occurs in immunocompetent adults. We observed a 3 month old infant who presented with marked atypical lymphocytosis and liver dysfunction. We examined serum samples to detect viral antibodies related to mononucleosis-like illness. Only the titers of antibody against human herpesvirus 6 were elevated. Primary human herpesvirus 6 infection cannot only cause exanthem subitum or present in an inapparent form but can also cause an illness like mononucleosis, even in an infant. PMID- 7793263 TI - Alpha-mannosidosis: the first Turkish case. AB - We describe a 10 month old boy with alpha-mannosidosis who presented with recurrent bronchopneumonia and diarrhea. Facial coarsening, deafness, hepatosplenomegaly, umbilical hernia, pectus carinatum and widespread Mongolian spots were distinguishing features. He also had mild skeletal deformities grouped together as 'dysostosis multiplex', and vacuolated lymphocytes on peripheral blood smear. These findings coupled with an abnormal urinary oligosaccharide pattern led to the suspicion of a lysosomal storage disease in the patient which proved to be alpha-mannosidosis. An exceptionally low level of alpha-mannosidase activity was subsequently found in serum and cultured skin fibroblasts. The patient's brother, who had died at the age of 10 months, had similar features. To the best of our knowledge, this is the first case reported from Turkey. PMID- 7793264 TI - Clinical features of Bardet-Biedl syndrome. AB - Six patients with Bardet-Biedl syndrome who have been followed in our clinics for the last 5 years are reported in this study. Of the five classic features of this syndrome; obesity and mental retardation were present in all cases, retinal disturbances were present in five, polydactyly in three and hypogenitalism was observed in all four male patients. Renal involvement, often suggested as a cardinal feature of this syndrome, was described in two patients. Iron deficiency anemia occurred in three patients, two patients were of short stature, one patient presented with an empty sella, and in two patients clinodactyly was detected. The results are compared to previously published literature and discussed. PMID- 7793265 TI - Child abuse and child abuse studies in Japan. AB - Medical research on child abuse has a short history of only 20 years. However, the social and familial changes that have occurred since the Second World War have resulted in an increasing number of abused children throughout Japan. Reported cases represent only the tip of the iceberg, with many cases being ignored. This article discusses the history, definition, incidence, and social, familial, and psychopathology factors in the etiology of child abuse based on clinical experience and research surveys undertaken during the past 20 years. Suggestions for improving child abuse preventive and reactive services are also made. PMID- 7793267 TI - Analysis of child abuse cases admitted in pediatric service in Japan. II. Backgrounds of child abuse in non-low birth-weight infants. AB - Child abuse of 126 non-low birth-weight (non-LBW) cases reported from pediatric clinics of major hospitals in Japan in 1986 were examined. Compared to LBW infants abused children's medical problems were few (25.4%) but the presence of step-parents and a history of rearing outside the home were evident (41.3%). The abuse of a child with medical problems by real parents showed similar characteristics to abuse of LBW, occurring at 0-1 and 4 years and two types of abuser's problems were apparent; one problem was the lack of child rearing ability and the other was the inability to cope with the stress involved in child rearing. In abuse of a child by step-parents, most abusers expressed emotional problems with their abused children. Child abuse by a real parent following a period of non-home care occurred soon after the child returned home, and abusers complained that the abused child did not take to its real parents. Abuse of a child without medical problems by real parents occurred at or around birth and indicated a poor ability to rear a child due to parental problems or low tolerance to cope with child rearing. Abuse both of a child and siblings by real parents implied a deficiency of understanding and inability in child rearing due to parental problems that may have resulted in abuse of the children at 0-1 year. It seems that two processes are critical in non-LBW child abuse as well as LBW child abuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793268 TI - Early intervention in case of child abuse: co-operation between the hot-line and local facilities. AB - The Center for Child Abuse Prevention (CCAP), a citizens' organization, was started in May 1991 with such members as pediatricians, psychiatrists, lawyers and people working at child welfare offices. A hot-line dealing with child abuse was set up immediately after the establishment of CCAP on 20 May 1991, and in the 2 years it has been in operation this hot-line has received 3189 calls out of which we picked 30 cases that CCAP was consulted about by helping persons or therapists affiliated with such facilities as hospitals, public health centers, etc. in order to evaluate how CCAP co-operates with these organizations. We reviewed the CCAP records of these 30 cases, comparing them with the materials concerning other hot-line calls, while at the same time interviewing the helping persons and therapists who had called in those cases, ascertaining their motives and the later course of the cases. This follow-up study was begun in June 1992 so that the longest follow-up period from the first call was 2 years and 7 months and the shortest 7 months. A total of 73.3% of these 30 cases required emergency intervention, and 53.4% were extremely severe, life-threatening cases of child abuse. The age distribution of these 30 victimized children peaked between 4 and 6, and 13 and 15 years. The perpetrator was the biological mother in 55.9% of the cases, the biological father in 29.4% and the stepfather in 8.9%. The abuse was physical in 58.3% of the cases, sexual in 8.9%, emotional in 5.6%, and involved neglect in 22.2%. These percentages differ from the general trend seen in the total hot-line cases, but were very similar to those reported by the Child Guidance Center. In the majority (56.7%) of the cases CCAP was consulted about, CCAP went beyond its hot-line service and co-operated to intervene, organizing network sessions in which the helping persons and therapists involved could discuss how best to deal with the problem at hand in five of these cases. In 22 of these 30 cases, the persons involved are still co-operating with CCAP after successful intervention through which the victimized children were rescued from critical situations. It is vitally important to set up networks between the professionals of the various support agencies involved if we are to intervene successfully in cases of child abuse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7793266 TI - Analysis of child abuse cases admitted in pediatric service in Japan. I. Two types of abusive process in low birth-weight infants. AB - A very high rate (43.0%) of low birth-weight (LBW) was shown in 331 abused/neglected cases reported from pediatric clinics of major hospitals in Japan. Of 87 LBW cases, 82.8% had medical problems and/or unsatisfactory reunion after non-home care and were abused at a particular age when each of the problems may have caused difficulties in caring. Two types of processes to abuse these intractable LBW were estimated: (i) abusers with psychiatric, mental problems or poor knowledge abused their children during the first 2 years, presumably because of an inability in child rearing; and (ii) abusers with neurosis or abnormal personality abused at ages over 2 years, complained of difficulties with rearing their children, and were suspected to be unable to cope with the difficulties. In both types, a combination of child and parental problems increased at risk. Obstetricians and neonatologists, who first encounter both high-risk mothers while pregnant and LBW, should give due care to the prevention of child abuse. PMID- 7793270 TI - Interpretation of child sexual abuse from the viewpoint of women's studies. AB - Child sexual abuse is interpreted as a triple infringement upon personal rights, and the nature of the problem of child sexual abuse is considered with regard to each of these three aspects, namely violence against women, child abuse and sexual assault. PMID- 7793271 TI - A boy with psychosocial short stature followed up from infancy to adulthood. AB - A boy with psychosocial short stature who has been followed up from the age of 11 months to adulthood is described. The boy was the product of an unwanted pregnancy. The emaciated short boy gained weight and height markedly during a short-term stay at hospital, but lost weight and experienced minimal height gain at home. On the fourth hospital admission at the age of 6 years 3 months the boy weighed 10 kg and measured 85.7 cm, he was malnourished and exhibited strange behavior and had a voracious appetite. He was examined endocrinologically and provocative tests performed early after admission showed insufficient growth hormone secretion, although this recovered later at a time of catch-up growth. The boy was reared in an orphanage from the age of 6 years 5 months until the age of 15 years 3 months. His growth rapidly caught up to a normal rate, his abnormal behavior disappeared, and he demonstrated an increased IQ. He attained 169.5 cm at the age of 17.5 years and possessed normal secondary sexual characteristics. After graduating from senior high school the patient has been living happily by himself without intervention from his mother, and is working in a Chinese restaurant. The impaired relationship between the boy and mother has never been restored. The record of growth and development described in this case is the longest ever reported. PMID- 7793269 TI - Child abuse viewed through the hot-line in Osaka, Japan. AB - Cases of child abuse identified by a hot-line telephone service and by a survey of health and welfare agencies are reported. Many consultations to the telephone hot-line were from mothers concerned about maltreating their own children. In such cases, the extent of abuse was often mild to moderate, and many of those mothers were troubled about child care in the relatively segregated context of the nuclear family. In only a few cases did the callers indicate that the children's life was in danger. In the administrative survey, however, deaths occurred in 5% of the cases, and the abused children frequently had physical and psychological symptoms. There were also more frequent and more serious family problems in the administrative survey compared to the telephone consultation cases. The findings of these surveys suggest that many children and parents are suffering from child abuse in Japan, that many cases are currently not being identified by health and welfare agencies, and that a wide range of measures, from protection of severely abused children to prevention of abuse, are necessary. PMID- 7793272 TI - Child ecology and child abuse as one of the new morbidities and new mortalities. PMID- 7793273 TI - Stable microbubble test for predicting the occurrence of respiratory distress syndrome. AB - To predict the development of respiratory distress syndrome (RDS) in premature neonates who might benefit from early administration of surfactant, the clinical applicability of stable microbubble (SM) test was prospectively evaluated. Fifty nine preterm neonates with the gestational ages of less than 37 weeks were studied. SM test was performed on gastric aspirates obtained within 30 minutes after birth. The number of microbubbles was correlated with later development of RDS. With a cut-off value of less than 10 microbubbles/mm2, the SM test showed a positive predictive value of 76.0% (19/25) and a negative predictive value of 97.1% (33/34), while sensitivity and specificity were 95.0% (19/20) and 84.6% (33/39), respectively. The overall accuracy was 88.1% (52/59). It was concluded that use of the SM test on gastric aspirates immediately after birth is a rapid, simple and reliable procedure for identifying those neonates with surfactant deficiency who may benefit from prophylactic surfactant therapy. PMID- 7793274 TI - Renal effects and urinary excretion of prostaglandin following indomethacin therapy in premature infants with patent ductus arteriosus. AB - Renal side effects and urinary prostaglandin were evaluated in 10 premature infants (Mean +/- SD: BW 1245 +/- 290 gm, GA 32 +/- 2.2 wks, Postnatal age 7.7 +/ 3.8 days) with significant PDA who were given one dose of indomethacin (0.3 mg/kg intravenously). There was a significant decrease in urinary output, osmolal and free water clearance after therapy. The fractional excretion of sodium, chloride, potassium, glomerular filtration rate and urinary prostaglandin E2 also decreased but were not statistically different from the baseline values. In infants who responded to indomethacin with ductus closure, their renal functions appeared to be preserved even though they had higher plasma indomethacin levels than the non-responders in whom significant changes in renal function were observed following indomethacin therapy. This observation suggested that the improved renal hemodynamics following the closure of the ductus may minimize or attenuate the renal side effects of indomethacin. PMID- 7793275 TI - Normal oscillometric blood pressure values in Chinese children during their first six years. AB - To establish normal blood pressure values, values of the upper arm blood pressure, heart rate, body weight, body length and thickness of skin fold over the deltoid area were measured in 3937 healthy children aged 1 day to 6 years. The cuff to measure the blood pressure was selected to cover a two-thirds length of the upper arm. Triple measurements of blood pressure and heart rate were obtained from infants younger than one year of age by an oscillometric device at supine position and in a quiet situation and at a sitting position from children older than one year. The average of blood pressure values (systolic/diastolic/mean) increased rapidly from 62.1/39.7/47.2 mmHg at age day one up to 72.7/46.9/56.6 mmHg at one week of life and up to 85.0/47.4/56.0 mmHg at age two months. After that, the blood pressure value (systolic/diastolic/mean) increased gradually with age. Blood pressure values (systolic/diastolic/mean) increased rapidly from 68.0/43.7/53.1 mmHg in children weighing less than 5 kg up to 87.6/41.8/59.8 mmHg in those weighing 5 to 10 kg; then values increased gradually with body weight. There were no significant differences in blood pressure and heart rate between boys and girls with different ages, different body lengths or different body weights. PMID- 7793276 TI - Radiofrequency catheter ablation of supraventricular tachycardias in pediatric patients. AB - Supraventricular tachycardia (SVT) is the most common cardiac arrhythmia in children. Atrioventricular (AV) reciprocating tachycardia utilizing an accessory pathway and AV nodal reentrant tachycardia (AVNRT) constitute a majority of SVTs. Radiofrequency energy ablation has recently become the treatment of choice in adults. Initial experience in pediatric patients in this Institute is reported in this study. Six consecutive patients (aged 5-22 years, mean age 13 years; 3 boys, 3 girls) with narrow-QRS SVT were studied from July to October in 1993. They had experienced symptomatic SVT for a mean period of five years (ranged from 1 to 15 years). Anti-arrhythmic agents, including beta-antagonists and calcium channel blockers, were unable to satisfactorily suppress these SVTs. Four of the six patients were shown to have a left-sided concealed accessory connection as the retrograde limb of the reentrant circuit. After identification of the earliest retrograde activation site, a steerable 7F catheter with a 4-mm-long electrode at the distal tip was placed within the left ventricle and positioned against the atrio-ventricular annulus. Another two patients were proved to have AVNRT. The ablation catheter was placed at the posterior/inferior aspect of the tricuspid annulus and guided by putative slow potential. Radiofrequency current was delivered at a power from 15 to 25W for four to six times with a mean duration of 40 seconds in patients with AV reciprocating tachycardia, and a single time in those with AVNRT. All six SVTs were successfully ablated. No complication was noted in any patient. Follow-up for three to seven months has indicated no recurrence of SVT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793278 TI - Ascariasis associated with acute pancreatitis in a child. AB - A six-year-old aboriginal girl living in northeast Taiwan, was admitted via Emergency Service with the chief complaint of epigastralgia for one day. Fever, leucocytosis, hyponatremia, acidosis and unilateral pleural effusion were noted. The serum amylase was 2976 U/L. Image studies including abdominal sonography and computerized tomography revealed a swollen and edematous pancreas. There was no evidence of previous trauma, drug using, hereditary problems, nor biliary tract stone; the patient was noted to have adult worms and eggs of Ascaris lumbricoides in stool and vomitus. Ascariasis associated with pancreatitis was suspected. She recovered completely after antihelmintic therapy (mebendazole) and supportive treatment. Fourteen ascarides and 20 trichurides were expelled during nine days of admission. PMID- 7793277 TI - The effect of recombinant human erythropoietin in treating the anemia of prematurity. AB - Anemia of prematurity (AOP) has been conventionally treated with erythrocyte transfusions. Recent investigations have reported the use of recombinant human erythropoietin (rHuEPO) as an alternative for treating AOP. The potential of rHuEPO in increasing erythropoiesis implies its clinical usefulness. The effect of rHuEPO on reticulocyte count as well as other parameters of blood cells was examined in 14 premature babies with AOP. The average birth body weight and gestational age of these premature babies were 1533.71 +/- 61.66 g (Mean +/- SEM) and 31.36 +/- 0.49 weeks respectively. They received the first dose of rHuEPO at age 26.14 +/- 2.03 days with a hemoglobin level by 9.40 +/- 0.27 g/dL and hematocrit level of 28.20 +/- 0.81%. They were given rHuEPO 200 U/kg subcutaneously every other day for 10 doses, and iron 3 mg/kg and vitamin E 25 IU/kg per os every day. Average erythropoietin level of the patients on entry into this study was low (7.66 +/- 1.10 mu/mL). After treatment with rHuEPO for 20 days, the corrected reticulocyte count increased from 0.64 +/- 0.10% to 1.68 +/- 0.42% on Day 5 (P < 0.05), 1.96 +/- 0.41% on Day 12 (P < 0.05), 1.77 +/- 0.43% on Day 20 (P < 0.05), and hematocrit increased from 28.2 +/- 0.81% to 29.58 +/- 1.02% (p < 0.05) on Day 20. Bone marrow aspirates on Day 10 for 9 infants revealed moderate to high cellularity, mostly with erythroblasts (47.89 +/- 1.78%); the M/E ratio was low (0.57 +/- 0.05). The granulocyte series and megakaryocyte could be well visualised.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793279 TI - Cerebral cryptococcosis in a child. AB - Reported is one case of cerebral cryptococcosis in a 12-year-old girl. The diagnosis was confirmed by the detection of Cryptococcus neoformans with both India ink preparation of the cerebrospinal fluid and Sabouraud's media culture. Clinical presentation included progressive severe headache, vomiting, left eye pain, diplopia, dizziness and unstable gait. Fever was absent as a symptom. Initial brain magnetic resonance imaging revealed a focal lesion over the right cerebellar hemisphere with better demonstration than contrast-enhanced computed tomography. The patient was treated with amphotericin B and 5-flucytosine with good final outcome. Early diagnosis and proper therapy are necessary in order to decrease the motality of cerebral cryptococcosis. PMID- 7793281 TI - Gianotti-Crosti syndrome associated with cytomegalovirus infection: report of one case. AB - A one and half a month-old infant, a female, was brought to this hospital with the chief problem of diarrhea lasting for more than one week. Four days after admission, symmetric and nonpruritic lichenoid papules developed over her face and limbs. Physical examination showed several small palpable lymph nodes over the bilateral inguinal areas, but without hepatosplenomegaly. Gianotti-Crosti syndrome was diagnosed. Latter on, cytomegalovirus (CMV) was isolated from urine and throat swab. It seemed that this case of Gianotti-Crosti syndrome was associated with CMV infection. PMID- 7793282 TI - Epilepsy as the sole manifestation of brain tumor--report of two cases. AB - Epilepsy may be the earliest and the sole clinical manifestation of a brain tumor. The existence and the character of the brain tumor cannot be predicted based solely on the severity and pattern of seizure. Epilepsy is common in patients with brain tumors, however, it is less common to find brain tumors in patients with epilepsy. Due to the slow progression of brain tumors and limitations in the use of brain computed tomography (CT), it often takes a long time to diagnose brain tumors in an epileptic child. Relief of epilepsy by surgical removal of the etiologic brain tumor appears to be promising. We report two cases of brain tumors presenting as intractable epilepsy with a discordant neuroimage. Therefore for those children taking long-term anticonvulsants with frequent recurrence, it appears reasonable to perform magnetic resonance imaging (MRI) to enable discovering of any organic lesions. PMID- 7793283 TI - Critical care medicine in pediatric. PMID- 7793280 TI - Serial ultrasonic changes of the bladder diverticulum during urination: report of one case. AB - A seven-year-old boy with a retrovesical diverticulum and ipsilateral renal dysplasia is reported. He had had a history of frequent urination and dysuria for four years. According to sonography, the volume of bladder diverticulum obviously changed during urination. The diverticulum presented as a temporary large reservoir of the bladder. In this case, serial ultrasonic changes assisted understanding of the role of the diverticulum during urination. PMID- 7793284 TI - Respiratory syncytial virus and bronchiolitis. AB - Viral bronchiolitis is a common world-wide disease of infants and children resulting in respiratory failure and occasionally death. The major underlying pathophysiology is airway inflammation of peripheral airways and airway hyperresponsiveness to bronchoprovocation. Management is primarily prevention through strict hand washing and avoidance of exposures during respiratory seasons, especially in small infants who have underlying heart or lung disease. Careful supportive therapy, including fluid hydration, good nutrition, and aerosolized bronchodilators, steroids or ribavirin may be helpful. Long term follow-up for these children is important because a significant number will have recurrent episodes of bronchiolitis and wheezing, and many will develop clinical asthma. There's some evidence that long term abnormalities of airway function, perhaps secondary to airway fibrosis, may result from bronchiolitis infections. Avoidance of exposure to passive smoking, cold air and air pollutants is also beneficial to long term recovery from RSV bronchiolitis. PMID- 7793286 TI - Multiple sclerosis in children: clinical, neuroimaging, and neurophysiological correlations. AB - Four female children with clinically-definite diagnoses of multiple sclerosis (MS) were studied with multimodal evoked potentials (EPs), electroencephalogram (EEG), cerebrospinal fluid (CSF) analysis, computed tomography (CT) and magnetic resonance imaging (MRI). Correlations among the clinical features, neuroimaging and neurophysiological studies were also evaluated. Their ages of the onset ranged from 5 to 11 years. The clinical evolution in the all four MS cases was relapsing-remitting form. MRI studies in three cases showed abnormal demyelinating plaques in the brainstem, cerebellum and white matter of the cerebrum. CT examination, performed in the other MS case, did not reveal hypodensic lesion. Despite that MRI failed to document optical nerve lesions, three cases had abnormal visual evoked potentials (VEPs). Somatosensory evoked potentials (SSEPs) were abnormal in three cases. Brainstem auditory evoked potentials (BAEPs) were abnormal in two cases presenting with signs of brainstem dysfunction. The conclusion was that paraclinical evidences obtained from MRI and multimodal evoked potential studies are of value as an aid in localizing involved areas and detecting silent lesions in children with MS. PMID- 7793285 TI - Relationship between hemodynamics and plasma atrial natriuretic peptide in children with ventricular septal defect or patent ductus arteriosus. AB - To evaluate the relationship between concentrations of ANP in plasma of the right sided central circulation and hemodynamic parameters in congenital heart disease with left-to-right shunt. We enrolled 20 children aged from 1 month to 4.8 years with ventricular septal defect (VSD) or patent ductus arteriosus (PDA). The concentrations of ANP in plasma were extracted through a cartridge (Sep-Pak C18) before being measured by radioimmunoassay. Significant increased concentrations of ANP in plasma from inferior vena cava (117.6 +/- 18.1 pg/mL), right atrium (160.6 +/- 21.6 pg/mL) to pulmonary artery (PA) (253.4 +/- 38.8 pg/mL) were recognized. In VSD (n = 10) and PDA (n = 10), the concentrations of ANP in plasma from the inferior vena cava correlated significantly with the ratio of pulmonary to systemic blood flow (Qp/Qs) (r = 0.69, p < 0.05; r = 0.94, p < 0.01 respectively), the systolic pulmonary artery pressure (r = 0.90, p < 0.01; r = 0.93, p < 0.01 respectively), the diastolic pulmonary artery pressure (r = 0.76, p < 0.02; r = 0.68, p < 0.05 respectively), and the mean pulmonary artery pressure (r = 0.88, p < 0.01; r = 0.87, p < 0.01 respectively). The concentrations of ANP in plasma from the pulmonary artery also correlated significantly with the Qp/Qs (r = 0.81, p < 0.01; r = 0.87, p < 0.01 respectively). The results indicated that left atrial volume loading may have an important influence on secretion of ANP in some congenital heart disease with left to right shunt. PMID- 7793287 TI - [Water uptake of tablets, their disintegration and dissolution are in close relation]. AB - Authors investigated the factors influencing this connection on phenylbutazone tablets. Tablets were prepared by wet granulation using three binders (gelatine, hydroxypropyl-cellulose, hydroxyethylcellulose) in different concentrations. Three disintegrants were compared (polyvinylpolypyrrolidon, formalin-casein and cyclodextrin polymer) on the basis of their disintegrating and dissolution enhancing properties. It was found, that the binder having surface activity improves the wetting of phenylbutazone tablets. Increasing the concentration of gelatine solution, tablets became harder, disintegrated very slowly and the active agent hardly dissolved. Among disintegrants the polyvinyl polypyrrolidon was found to be the best. This material increases the hardness and the drug release as well. The use of cyclodextrin polymer is limited because of the slow water uptake of its tablets. The water uptake of nondisintegrating tablets was described with the Washburn equation. Water penetrates into disintegrating tablets according to the Weibull distribution. The penetration rate can be characterized with the "characteristic water penetration time (t63.2%), obtained from the Weibull equation. The difference between nondisintegrating and disintegrating tablets can be observed in the dissolution kinetic, too. The drug dissolves from the nondisintegrating tablets according to Noyes-Whitney equation (Eq. 1.), from disintegrating tablets according to the modified Noyes-Whitney equation (Eq. 2.) or Weibull equation (Eq. 3.). The dissolution rate constant (K) obtained from the modified Noyes-Whitney equation is proportional with water uptake and in inverse. PMID- 7793288 TI - [Polymer-containing eyedrops. III. Surface tension of polymer solutions]. AB - Therapeutical effect of ophthalmological solutions is markedly influenced by their surface tension which is also responsible for the irritating effect of the eye drop. Authors studied the effect of different polymers on surface tension. They found that each of the water soluble polymers studied decreased the surface tension of solutions against air. This surface tension decreasing effect is independent from the concentration of the solution. Its value is slightly influenced by the pH of the solution, while it is increased by its electrolyte content. PMID- 7793289 TI - [Production technology and in vitro study of rectal suppositories containing chloroquine phosphate]. AB - Chloroquine-phosphate was suspended in various lipophilic and hydrophilic suppository bases in an amount of 250 mg/2.0 g. The authors studied the solidity and the disintegration time of the suppositories as well as the in vitro drug liberation with a membrane diffusion method. The effect of the storage time and the storage circumstances on the stability of the suppositories was observed. Tropics-resistance studies were also carried out at a temperature of 45 degrees C and at a relative humidity content of 75%, thus these suppositories may be used for the treatment of malaria. The Witepsol H 15 base was found to be the best in all respect for use in countries with a continental climate. Finally a function relationship was found between the concentration of the pharmacon and the diffusion time with linear regression analysis. PMID- 7793290 TI - [Thermostability of the structure of creams and gels. I. Investigation of hydrophilic creams containing Hostaphat emulsions]. AB - The effect of temperature on the change of structure of creams containing Hostaphat emulsifiers has been investigated. The micelles consisting of hydrophilic and liphophilic surfactants are disintegrated and desolvatated on the effect of heat, therefore the evaporation of water can be resulted. This theory was verified by the correlation between rheological data and the results of derivatographic measurements. It has been established that the hydrophilic emulsifier plays an important role in thermostability. PMID- 7793292 TI - VI Congress of the Bulgarian Physiological Society. Basic Mechanisms of Regulation in the Organism under Normal and Pathologic Conditions. Sofia, June 8 9, 1995. Abstracts. PMID- 7793291 TI - [Preparation and investigation of liposomes]. AB - Vesicles dispersed in an aqueous milieu and containing a phospholipid double layer are used primarily in cosmetic and dermatological preparations, though experiments are under way to use them as carriers of diagnostics and medicines. Different parenteral and dermatological drug preparations are already in circulation worldwide. Researchers have hopes of using them for the lyophilization of lipophobic pharmacons, to prolong medicinal effects, for the active and passive targeting of drugs etc. The first steps of liposome research started in 1965 and we now know much about liposome technology and their use in therapy, but various questions remain to be answered. On the level of basic research, this paper investigates the preparation of liposomes and characteristics influencing their stability. PMID- 7793293 TI - The Comprehensive Assessment List for Affective Disorders (COALA): a polydiagnostic, comprehensive, and serial semistructured interview system for affective and related disorders. AB - This supplement describes the development and structure of the Comprehensive Assessment List of Affective Disorders (COALA) system, which was recently developed for a collaborative follow-up study of a broad spectrum of affective disorders in Japan and which consists of a series of semistructured interviews for affective and related disorders. The COALA distinguishes itself from the extant semistructured interviews by being able to provide polydiagnostic, comprehensive and serial assessments. It is polydiagnostic because it derives diagnoses according to 29 historical and modern diagnostic systems through computer algorithms. It is comprehensive because it not only depicts the symptoms profile and rates their severity according to various endogenicity indices and severity rating scales but also measures, in the psychosocial domain, the life events and their characteristics. In addition, it has sections for past illnesses and family history. It is serial because the system includes follow-up semistructured interviews that can be administered monthly and that monitor changes in the psychopathological and psychosocial features. The theoretical underpinnings of the COALA system, especially its polydiagnostic approach to a broad spectrum of affective disorders and its treatment of psychosocial factors, are discussed in view of recent proposals for the future nosological research. The findings of the interrater reliability study (n = 107) are also presented, with satisfactory to excellent results for almost all of the psychopathological and psychosocial variables, all of the composite severity ratings and most of the polydiagnostic evaluations. PMID- 7793295 TI - Impaired luteinizing hormone responsiveness to gonadotropin-releasing hormone in the inferior petrosal sinuses of hyperprolactinemic patients. AB - The aim of this study was to evaluate serum baseline and gonadotropin-releasing hormone (GnRH)-stimulated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations in the inferior petrosal sinuses and in peripheral blood in nine normoprolactinemic and eight hyperprolactinemic patients who were being subjected to perihypophyseal phlebography for diagnostic purposes or neurosurgical indications. Serum FSH and LH concentrations were significantly higher in both inferior petrosal sinuses than in peripheral blood (p < 0.001 and p < 0.05, respectively) in normoprolactinemic but not in hyperprolactinemic patients. Additionally, in normoprolactinemic patients, the LH response to intravenous bolus GnRH in the inferior petrosal sinuses (evaluated as peak/basal) was significantly greater than in hyperprolactinemic patients (p < 0.01). No difference was found as far as FSH response to GnRH was concerned. In conclusion, these findings suggest that the hypogonadism of hyperprolactinemic patients may depend on the impaired release of LH at the pituitary level. PMID- 7793294 TI - Evidence for a role of neurosteroids in modulation of diurnal changes and acute stress-induced corticosterone secretion in rats. AB - The neurosteroid allopregnanolone has been shown to be a potent ligand of gamma aminobutyric acid (GABA)-A receptors and enhances its receptor-mediated inhibitory events. Since central GABA plays a major inhibitory role, via GABA-A receptors, in hypothalamic-pituitary-adrenal (HPA) function in rats, the present study has evaluated the effect of passive immunoneutralization of allopregnanolone on diurnal changes in corticosterone secretion and acute stress induced corticosterone secretion in rats. In the first protocol, four groups of male rats (prepubertal, fertile, castrated adult and aged) and three groups of female rats (prepubertal, fertile at different phases of the estrous cycle and aged) were studied. Rats were injected intracerebroventricularly (i.c.v.) with 10 microliters anti-allopregnanolone serum or 10 microliters normal rabbit serum (control) 24 h before exposure to an acute cold swimming stress, and sacrificed either before stress or after 5 min stress. In the second protocol, fertile male or female rats at diestrus II were injected i.c.v. with anti-allopregnanolone serum or normal rabbit serum and sacrificed on the following day at 10.00 or 18.00. Truncal blood samples were collected for measuring plasma corticosterone. Our results showed that there was no significant difference in basal plasma corticosterone levels between antiserum-treated and control rats of both sexes. However, in male rats, central injection of antiserum to allopregnanolone significantly potentiated plasma corticosterone response to stress in prepubertal and adult fertile rats as well as in castrated rats. Likewise, in female rats, the stress response of plasma corticosterone was enhanced by passive immunoneutralization of allopregnanolone in prepubertal and fertile rats throughout the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793296 TI - The influence of DHEA on serum lipids, insulin and sex hormone levels in rabbits with induced hypercholesterolemia. AB - The authors estimated the influence of dehydroepiandrosterone (DHEA) administration, a potential antiatherogenic agent, on serum lipids, sex hormones and insulin levels in male rabbits fed on an atherogenic diet. They concluded that (1) DHEA administration has an unfavorable impact on the serum lipid profile; (2) an atherogenic diet causes insulin resistance; (3) the glucose and insulin levels are not related to DHEA in normally fed rabbits and in rabbits with hyperlipoproteinemia; (4) an atherogenic diet causes a slight increase of estradiol concentration; (5) DHEA treatment has no significant effect on testosterone and estradiol concentrations in both normally fed rabbits and those on an atherogenic diet; (6) DHEA administration has an anti-obesity effect. PMID- 7793297 TI - Effects of danazol and medroxyprogesterone acetate on estrogen-(estradiol and estriol) specific binding sites in rabbit uterus. AB - In rabbit uterus, the presence of separate specific binding sites for not only estradiol but also estriol has been proposed. These sites may be correlated with an antiestradiol effect. Therefore, this study was designed to investigate the effect of antiestrogenic agents such as danazol and medroxyprogesterone acetate (MPA), especially on the estriol binding sites. Danazol and MPA in combination with estradiol were administered subcutaneously to immature female rabbits daily for 10 days, and resulted in a significant (p < 0.05) decrease in uterine weight and estradiol binding sites in the uterus. Treatment with MPA significantly (p < 0.05) decreased the level of estriol binding sites, but treatment with danazol resulted in this to a minimal extent in the uterus primed by estradiol. MPA did not bind to estradiol and estriol binding sites, while danazol at a high concentration bound to estriol binding sites with some affinity, but not to estradiol binding sites in the uterine cytosol of estrogen-primed rabbits. These results suggest that within the antiproliferative effect of danazol and MPA (an antiestrogenic action on estrogen-stimulated uterine growth) there are likely to be specific differences between some of the possible mechanisms of danazol and MPA in their action at the estriol binding site. PMID- 7793298 TI - Sensitivity of plasma insulin levels in obese and non-obese women with functional hyperandrogenism. AB - Hyperinsulinemia has been implicated in the etiology of functional hyperandrogenism (FH). In a prospective controlled trial, we determined the sensitivity and diagnostic accuracy of fasting plasma insulin levels in 37 females of reproductive age with FH, who were further subdivided into obese (body mass index (BMI) > 25 kg/m2, n = 22) and non-obese (n = 15) groups, in women with (n = 30) and without (n = 7) polycystic ovaries on vaginal endosonography and in controls of similar age (n = 29) who were body mass-matched to the non-obese FH subgroup. Insulin, testosterone, androstenedione, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio and dehydroepiandrosterone sulfate (DHEA-S) levels were measured by conventional radio-immunoassay. All hormonal parameters, including insulin (p , 0.0001), were significantly increased in the FH group vs. controls. Mean BMI and insulin did not differ between the subgroups with and without polycystic ovaries. Only insulin was increased (p = 0.0012) in the obese FH vs. non-obese FH subgroup. In the FH group, insulin showed the highest coefficient of variation (0.76) but also the best sensitivity (0.57) and diagnostic accuracy (0.73), equal that of testosterone (0.54 and 0.73, respectively). Insulin was more sensitive (0.72) than testosterone (0.59) in the obese FH subgroup, but less sensitive (0.27) than testosterone (0.47) in the non obese FH subgroup. Multiple correlation analysis showed a significant linear relationship (p < 0.0001) between insulin and BMI but no correlation between insulin and the other parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793299 TI - Insulin secretion in obese and non-obese women with polycystic ovary syndrome and its relationship with hyperandrogenism. AB - Insulin resistance has been reported to be associated with hyperandrogenism and polycystic ovaries. To study the prevalence of insulin resistance in patients with polycystic ovary syndrome (PCO) and the correlation between hyperinsulinemia and hyperandrogenism, 48 patients were divided into four groups: group 1, non obese ovulatory women (n = 10); group 2, obese ovulatory women (n = 9); group 3, non-obese women with PCO (n = 14); group 4, obese women with PCO (n = 15). Each patient was submitted to an oral glucose tolerance test (OGTT). Glucose, insulin, androstenedione and testosterone levels were determined and the blood glucose and insulin response of women with PCO and normal women were compared. Glucose intolerance was observed in group 3 (28.6%) and group 4 (40%) but not in groups 1 or 2, and hyperinsulinemia was observed in group 2 (66.7%), group 3 (64.3%) and group 4 (86.6%). There was a correlation between androstenedione and testosterone levels and insulinemia in group 4. There was also a high prevalence of insulin resistance in patients with PCO regardless of obesity, and hyperandrogenism aggravated insulin resistance. PMID- 7793300 TI - Hormonal profiles in successful and unsuccessful implantation in IVF-ET after combined GnRH agonist/gonadotropin treatment for superovulation and hCG luteal support. AB - The luteal phase of in vitro fertilization-embryo transfer (IVF-ET) cycles has come under great scrutiny as the cause for the discrepancy between fertilization rates (> 70%) and pregnancy rates (around 20%) in most IVF programs is sought. The effects of the various stimulation protocols on the subsequent hormonal events of the luteal phase are both important and controversial but information regarding cycles where ovarian stimulation has been carried out with gonadotropins under pituitary suppression is scanty. The effect of high levels of estrogen in the late follicular phase and around the time of implantation is a matter of concern. As combined gonadotropin-releasing hormone analog (GnRH-a) gonadotropin treatment for superovulation is associated with supraphysiological ovarian steroid levels, both in the follicular and luteal phase of IVF cycles, we compared preovulatory (estradiol), midluteal (estradiol, progesterone and prolactin) and late luteal (estradiol and progesterone) hormone levels in on going pregnancies, abortions and non-conception cycles in 222 patients accomplishing their first IVF-ET attempt who received such ovarian stimulation therapy. For both successful and unsuccessful implantation cycles, estradiol on the day of human chorionic gonadotropin (hCG) administration correlated positively with progesterone and estradiol levels and negatively with the progesterone/estradiol ratio in the midluteal phase. Mean peak follicular estradiol, midluteal estradiol and progesterone levels, mean mid- and late luteal progesterone/estradiol ratio, and mean midluteal prolactin concentration, were similar in the three groups studied. The mean late luteal estradiol and progesterone in the on-going pregnancy group were significantly higher than in non-conception cycles (p < 0.005 and p < 0.001, respectively) as a reflection of trophoblastic hCG production. Forty-eight patients (21.6%) had hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793301 TI - The results of an in vitro fertilization program: two regimens of superovulation. AB - Gonadotropin-releasing hormone (GnRH) agonists are increasingly used in ovarian hyperstimulation protocols in in vitro fertilization (IVF) programs. From March 1992 to June 1993, 565 patients attending our Institute underwent superovulation in 1104 IVF program cycles. Of these cycles, 650 were stimulated with clomiphene citrate and gonadotropins (human menopausal gonadotropin/hMG), and 454 with the GnRH agonist buserelin and hMG in a group of patients who had earlier failed to respond or did not conceive after clomiphene citrate/hMG stimulation. The ovarian response was similar in both groups, however, with the use of buserelin more oocytes were recovered -4.9 +/- 3.2 and 3.5 +/- 2.3 oocytes, respectively. The clinical pregnancy rate per transfer in the group of patients superovulated with buserelin/hMG was twice that of the clomiphene citrate/hMG group (21.0% vs. 10.4%). The relatively high pregnancy rate with the buserelin/hMG regimen in the group of 'poor responders' may be connected with GnRH agonist-induced pharmacological hypophysectomy and the sequelae thereof: normalization of some endocrinopathies, absence of an endogenous luteinizing hormone (LH) surge and better endometrium receptivity, oocytes and embryo quality. PMID- 7793302 TI - Ethinylestradiol from contraceptive formulations and the ovarian response: an estrogen dose-dependency on natural estradiol concentrations. AB - To evaluate the competitive molecular phenomenon of ethinylestradiol from contraceptive formulations vs. endogenous 17 beta-estradiol in the intra- and extracellular compartments, a descriptive analysis was performed. Plasma and endometrial samples were simultaneously obtained on different days of the pseudomenstrual cycle from oral contraceptive users taking ethinylestradiol/norgestrel (30 micrograms/500 micrograms; n = 13) and ethinylestradiol/norethindrone (50 micrograms/1.0 mg; n = 14) in order to quantify the 17 beta-estradiol concentrations. From our results the chronic administration of these combined oral contraceptives demonstrated that the lower component ethinyl-estradiol (30 micrograms) does not compete substantially at the circulating level, permitting concentrations of natural estradiol such as those seen during follicular maturation in the ovulatory cycle. However, in the endometrium such a cyclicity is not seen, thus the possibility of a local infertility effect should be reconsidered to enable the investigation of a different approach in future methods of contraception. PMID- 7793303 TI - Potential impact on breast cancer risk of circulating insulin-like growth factor I modifications induced by oral HRT in menopause. AB - Unlike parenteral estrogens, oral estrogen administration in menopause causes, through its hepatocellular action, a significant decrease of circulating insulin like growth factor I (IGF-I) levels; this effect is opposed by the addition of an androgenic progestogen. In vitro studies show that IGF-I is a potent mitogen for 'estrogen responsive' breast cancer cells. Moreover, some findings in breast cancer patients and in women treated with tamoxifen suggest that reduction of circulating IGF-I could be protective to the breast. However, by also considering (1) the potential action on breast cancer cells of IGF-II, (2) the possible consequences of the growth hormone (GH) increase caused by the IGF-I reduction and (3) the fact that in vitro results are not simply transferable to the in vivo condition, other 'scenarios' can be envisaged, besides the favorable one. In support of the latter, there are epidemiologic data which suggest that oral estrogen use could have some favorable peculiarities with regards to breast cancer risk. The associated decrease in circulating IGF-I level could well be one of these peculiarities. PMID- 7793306 TI - Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection. AB - Transection of the fimbria-fornix bundle in adult rats results in degeneration of the septohippocampal cholinergic pathway, reminiscent of that occurring in aging as well as Alzheimer disease. We report here a study of the effect of a treatment with acetyl-L-carnitine (ALCAR) in three-month-old Fischer 344 rats bearing a partial unilateral fimbria-fornix transection. ALCAR is known to ameliorate some morphological and functional disturbances in the aged central nervous system (CNS). We used choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) as markers of central cholinergic function, and nerve growth factor (NGF) levels as indicative of the trophic regulation of the medio-septal cholinergic system. ChAT and AChE activities were significantly reduced in the hippocampus (HIPP) ipsilateral to the lesion as compared to the contralateral one, while no changes were observed in the septum (SPT), nucleus basalis magnocellularis (NBM) or frontal cortex (FCX). ALCAR treatment restored ChAT activity in the ipsilateral HIPP, while AChE levels were not different from those of untreated animals, and did not affect NGF content in either SPT or HIPP. PMID- 7793305 TI - Cortisol levels alter the response to metoclopramide in patients with hypothalamic amenorrhea. AB - The reduction in frequency and/or amplitude of gonadotropin-releasing hormone (GnRH) pulses in patients with amenorrhea of hypothalamic origin has been attributed to increased dopamine activity. The objective of the present study was to determine the role of dopamine in the pathogenesis of hypothalamic amenorrhea. Fourteen patients with hypothalamic amenorrhea, nine of whom had psychogenic amenorrhea and five anorexia nervosa, were studied and compared with nine normal women during the early follicular phase. Metoclopramide (10 mg), a dopamine antagonist, was infused intravenously and blood samples were collected at 15-min intervals for 2 h for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) measurement by radioimmunoassay. Both the hypothalamic amenorrhea (psychogenic amenorrhea and anorexia nervosa) and control groups were unresponsive to FSH, suggesting that dopamine may have little or no effect on FSH secretion. Five patients of the psychogenic amenorrhea group responded to LH (responsive psychogenic amenorrhea) and four did not (non-responsive psychogenic amenorrhea). No anorexia nervosa or control patient responded to the stimulus. Responsive psychogenic amenorrhea patients showed decreased basal cortisol levels compared to the non-responsive psychogenic amenorrhea and anorexia nervosa groups. It is possible that patients with exclusive alterations in the dopaminergic system are those who respond to metoclopramide (responsive psychogenic amenorrhea group), whereas patients who also have involvement of the hypothalamic-adrenal axis like the women with anorexia nervosa, are not responsive to metoclopramide and tend to have elevated cortisol levels. The non responsive psychogenic amenorrhea group, with elevated cortisol levels, probably represents an intermediate step between the responsive psychogenic amenorrhea and anorexia nervosa patients. PMID- 7793304 TI - Sex hormones, the menopause and urinary problems. AB - To date, there have been few appropriate placebo-controlled studies using both subjective and objective parameters to assess the efficacy of estrogen therapy for the treatment of urinary incontinence. Further confusion arises from the heterogeneity of different study protocols. Consequently, the best treatment in terms of type and dose of estrogen and route of administration is unknown. From these studies, however, there is clear evidence to suggest that recurrent urinary tract infection can be prevented or even treated by the use of estrogen therapy. Furthermore, systemic estrogen replacement appears to alleviate the symptoms of urgency, urge incontinence, frequency, nocturia and dysuria, and low-dose topical estrogen is effective in the management of atrophic vaginitis. Although the latter example appears to be free from side-effects, even following prolonged administration, it is unclear whether low-dose therapy has a sufficient effect on the lower urinary tract to treat urinary incontinence. There is no conclusive evidence that estrogen replacement alone is sufficient to cure stress incontinence, but in combination with an alpha-adrenergic agonist there may be a role for estrogen therapy in the conservative management of genuine stress incontinence. On the other hand, estrogen supplementation definitely improves the quality of life of many postmenopausal women and, therefore, makes them better able to cope with other disabilities. Perhaps the role of estrogen in the management of postmenopausal urinary disorders is as an adjunct to other methods of treatment such as surgery, physiotherapy and drugs. This is certainly a hypothesis which should be tested. PMID- 7793307 TI - Evidence of internucleosomal DNA fragmentation and identification of dying cells in X-ray-induced cell death in the developing brain. AB - Newborn Sprague-Dawley rats received a single dose of 2 Gy X-rays and were killed 6 hr later. Dying cells were characterized by extreme chromatin condensation and nuclear fragmentation. Dying cells were distributed in the primary and secondary germinal zones and in other brain regions. Among these latter, dying cells occurred in the cortical layers of the olfactory bulb, layers II-III and VIb of the neocortex, piriform and entorhinal cortex, stratum oriens and pyramidale of the hippocampus, striatum, thalamus, amygdala, brainstem, internal granular layer of the cerebellum, and cerebral and cerebellar white matter. Dying cells were immature cells, neurons and glial cells (including radial glia). In-situ labeling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. Since the number of cells stained with this method was larger than the number of dying cells, as revealed with current histological techniques, it is suggested that nuclear DNA fragmentation precedes chromatin condensation and nuclear fragmentation in X-ray-induced apoptosis. Furthermore, agarose gel electrophoresis of extracted DNA from irradiated brains showed a "ladder" pattern which is typical of internucleosomal DNA fragmentation and endonuclease activation. PMID- 7793308 TI - Expression of basic fibroblast growth factor and its receptors in human fetal microglia cells. AB - The presence of basic fibroblast growth factor (bFGF) and FGF receptors was investigated in microglia cells derived from human fetal brain long-term cultures. Production of bFGF was suggested through the capability of microglial extracts to stimulate plasminogen activator (PA) synthesis in endothelial cells. The identity of PA-stimulating activity with bFGF was confirmed by its high affinity for heparin and its cross-reactivity with polyclonal antibodies to human recombinant bFGF. These antibodies recognized a cell-associated M(r) 18,000 protein as well as trace amounts of the M(r) 24,000 bFGF isoform in Western blot. All microglial cells showed bFGF immunoreactivity in the cytoplasm and, sometimes, in the nucleus. Scatchard plot analysis of 125I-bFGF binding data revealed the presence of low affinity heparansulphate proteoglycans (380,000 +/- 60,000 sites/cell; Kd = 730 +/- 200 nM) and of high affinity tyrosine-kinase receptors (10,300 + 2500 sites/cell; Kd = 30 +/- 9 pM). Immunocytochemistry confirmed the presence of FGF receptor (1/flg) on the cell surface of some, but not all microglial cells, with prevalent association to ameboid microglia. Transcripts for FGF receptors 1, 2, 3 and 4 were found in microglia by Northern blot analysis. Co-expression of bFGF and its receptors in human fetal microglia suggests an autocrine role of bFGF in these cells. PMID- 7793309 TI - Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats. AB - To investigate the relationship between neural activity and cerebral energy metabolism during anoxia or ischemia in neural tissue of different ages, hippocampal slices were prepared from four-, seven- and 10-day-old and adult rats. For the index of the neural activity, the population spikes were recorded in the pyramidal cell layer of the CA3 area. ATP and phosphocreatine levels in the slices were measured during oxygen and/or glucose deprivation. After deprivation of both oxygen and glucose, population spikes of the slices from four, seven- and 10-day-old and adult rats ceased completely in 14.2, 11.8, 9.4 and 5.3 min, respectively. The level of ATP at the time of cessation of population spike in four-, seven- and 10-day-old and adult rats was 37.4, 30.2, 28.5 and 56.4% of the original concentrations. After deprivation of glucose only, the decay time of the population spikes of the slices from four-, seven- and 10 day-old and adult rats was 17.8, 14.5, 9.0 and 10.0 min and at the time of population spikes cessation the level of ATP was 99.8, 84.2, 79.3 and 49%, respectively. After deprivation of oxygen only, population spikes of the slices from four, seven- and 10-day old and adult rats ceased completely in 257, 283, 109 and 8.5 min, respectively. The level of ATP at the time of population spikes cessation was 50, 40, 36.6 and 94.4% of the initial values, respectively. These results indicate that the immature rat is extremely resistant to oxygen deprivation from a functional and a metabolic view, whereas in the adult rat, preservation of neural activity depends much on both oxygen and glucose. During glucose deprivation, population spikes of the slices of immature and mature rats ceased rapidly although the level of ATP is preserved at high levels. This suggests that glucose plays an important role in the preservation of neural activity in addition to its major function as an energy substrate especially in immature animals. PMID- 7793310 TI - Enhanced survival and differentiation in vitro of different neuronal populations by some interleukins. AB - Data from the literature demonstrate the existence of a growing family of neuropoietic cytokines; members of this group have structural motifs in common with other members and with neurotrophic factors. In this research we studied the responses elicited in vitro by some of these molecules in two different neuronal populations: murine neuroblastoma N18TG2 and neurons from chicken dorsal root ganglia. Both IL-2 and IL-6 improve the survival of murine neuroblastoma cells in clonal density plating experiments; in addition IL-2 significantly inhibits thymidine incorporation by single cell suspension. The survival of sensory neurons, on the other hand, non-responsive to IL-2 and IL-6, was significantly supported by IL-3, which also stimulates their morphological differentiation, inducing the formation of a well-developed neural net. In conclusion, results reported here confirm the neurotrophic activity of some ILs and provide additional neuronal models for future investigations. PMID- 7793311 TI - Basic fibroblast growth factor (bFGF) increases the survival of embryonic and postnatal basal forebrain cholinergic neurons in primary culture. AB - Basic fibroblast growth factor (bFGF) is found in high concentrations in the mammalian central nervous system. It is a mitogen for glia and it influences the development and survival of specific populations of neurons. In this study, we investigated the effect of various concentrations of bFGF on the survival of embryonic and postnatal cholinergic basal forebrain neurons plated at low and high density in the presence and absence of glia. We observed that 50 and 100 ng/ml of bFGF increased the survival of embryonic cholinergic neurons plated at high density. This effect was observed only in the presence of glia. Lower concentrations of 10 and 20 ng/ml had no effect on cholinergic neuronal survival. The number of GFAP (glial fibrillary acidic protein)-positive cells in high density embryonic cultures was increased by all concentrations of bFGF. In low density embryonic cultures, an increase in cholinergic neuron survival was observed at concentrations ranging from 20 to 100 ng/ml. The number of GFAP positive cells in low-density cultures was also increased by all concentrations of bFGF. Similar to low-density embryonic cultures, the survival of cholinergic neurons from postnatal day 2 cultures was significantly increased in the presence of glia at concentrations of 20, 50 and 100 ng/ml of bFGF. Postnatal glia was affected by all concentrations of bFGF, as was observed in embryonic cultures. This study indicates that high concentrations of bFGF can influence cholinergic neuronal survival by stimulating and increasing glia, which may produce factor(s) that are necessary for cholinergic neuron survival. PMID- 7793312 TI - The adventures of a biologist: prenatal diagnosis, hematopoiesis, leukemia, carcinogenesis, and tumor suppression. PMID- 7793314 TI - Cyclins and cyclin-dependent kinases: theme and variations. PMID- 7793315 TI - Molecular genetics of 11q23 chromosome translocations. PMID- 7793316 TI - Role of scatter factor and the c-met protooncogene in the pathogenesis of AIDS associated Kaposi's sarcoma. AB - Kaposi's sarcoma is a highly lethal tumor in patients with sexually acquired AIDS. A number of etiologic agents have been implicated in the development of this disease in this patient population and there is ample evidence that aberrant production of and responsiveness to KS tumor and host cell-derived cytokines plays a central role in the pathogenesis of AIDS-KS. In this review we propose that aberrant expression SF and c-met is central to the pathogenesis of KS. KS is a serious and life-threatening consequence for many patients with AIDS. Unfortunately, current therapeutic strategies for the treatment of this complex neoplasm have met with only limited success. In view of the poor survival rates for AIDS-KS patients which continue to decline at an alarming rate, it is eminently clear that a better understanding of the etiology and pathogenesis of this form of KS is needed if novel therapeutic strategies designed to successfully combat this disease are to be developed. If our hypothesis is validated, one could envision several approaches whereby the modulation of SF/c met function or production might lead to a reduction in the incidence and severity of KS lesions. Antibody therapy directed against either SF-producing tumor cells or against the c-met receptor might decrease the incidence of new tumors by limiting their clonal expansion and lead to regression of established tumors by blocking SF-mediated tumor cell proliferation and neovascularization. It might also be possible to suppress production of SF or accessory cytokines involved in the induction SF production and thus short circuit SF/c-met growth promoting effects. We have outlined a novel hypothesis for understanding the mechanism underlying the development of AIDS-associated KS. This is most certainly not the whole story, however. Clearly, other cytokines and alterations in natural host defenses and the immune system contribute significantly to the development of AIDS-associated KS. We believe, however, that recognition of SF/c met as a participant in this disease is necessary if we are to more fully understand the pathogenesis of AIDS-associated KS. PMID- 7793313 TI - p53: a cell cycle regulator activated by DNA damage. PMID- 7793317 TI - Rel/NF-kappa B/I kappa B story. PMID- 7793318 TI - Radiation leukemia virus-induced leukemogenesis: a paradigm of preleukemia and its control by preventive therapy. PMID- 7793319 TI - The insertion of foreign DNA into mammalian genomes and its consequences: a concept in oncogenesis. PMID- 7793320 TI - From Aristotle, through Spemann, to tumor immunology: a personal experience. PMID- 7793321 TI - Tumor suppressor p53 mutations and breast cancer: a critical analysis. AB - Alterations in the tumor suppressor gene p53 are the most commonly identified changes in cancer, including neoplasia of the breast. The activity of p53 is regulated post-translationally. Phosphorylation state, subcellular localization, and interaction with any of a number of cellular proteins are likely to influence the function of p53. The exact effect of p53-mediated growth suppression seems to be cell-type specific but appears to be directly related to the ability of p53 to act as a specific transcriptional activator. The role that transcriptional repression plays in the function of WT p53 is less clear. It is also possible that p53 has a more direct activity in DNA replication and repair. Most documented p53 mutations result in single amino acid substitutions which may confer one or more of a spectrum of transforming abilities on the protein. Mutation may lead to nuclear accumulation of p53 protein; however, inactivation of p53 by nuclear exclusion and interaction with the mdm2 protein also appear to be important in tumorigenesis. Used in conjunction with other established factors, accumulation of cellular p53 may be a useful prognostic indicator in breast cancer. A syngeneic mouse model system yielded evidence that p53 mutations are important in the early, preneoplastic stages of mammary tumorigenesis. This murine system may provide the ability to investigate the functions of p53 in the early stages of breast cancer which are technically difficult to examine in the human system. PMID- 7793322 TI - Apoptosis in viral infections. PMID- 7793323 TI - Membrane fusion and the alphavirus life cycle. PMID- 7793324 TI - Equine herpesviruses 4 (equine rhinopneumonitis virus) and 1 (equine abortion virus). PMID- 7793327 TI - Characterization of genome structure and establishment of vector cell lines for plant reoviruses. PMID- 7793326 TI - Feline immunodeficiency virus as a model for development of molecular approaches to intervention strategies against lentivirus infections. PMID- 7793325 TI - Bovine herpesvirus 1 (BHV-1): biology, pathogenesis, and control. PMID- 7793328 TI - Bacteriophage PRD1: a broad host range DSDNA tectivirus with an internal membrane. PMID- 7793329 TI - Modification of membrane permeability by animal viruses. PMID- 7793330 TI - Are elderly Asians in Britain at a high risk of vitamin D deficiency and osteomalacia? AB - Many studies have shown the indigenous elderly population and Asian immigrants to be groups at particular risk of vitamin D deficiency and osteomalacia, but there are no data on the risks in elderly Asians. In this community-based study a group of elderly Asians was compared with control groups of elderly and young whites and young Asians. Levels of 25-hydroxyvitamin D3 (25-OHD3) were significantly lower (p < 0.0001) in elderly Asians (21/37) and young Asians (7/17) compared with white controls. The difference in parathyroid hormone (PTH) between Asians and whites was also significant (p < 0.0007) as was that between young and old (p < 0.0002). Abnormal PTH and 25-OHD3 (high PTH and low 25-OHD3), indicative of a high risk of osteomalacia, occurred in 22% of elderly Asians compared with 6% of elderly whites. The calcium, phosphate and alkaline phosphatase were normal in all individuals. Among the Asians, vegetarianism was not related to lower 25-OHD3 levels. Symptoms suggestive of osteomalacia were more common (p < 0.05) in elderly Asians than in their white counterparts. This first study of 25-OHD3 levels in community-resident elderly Asians suggests that more than half were low, placing them at a significantly higher risk of osteomalacia. PMID- 7793331 TI - Upper-extremity motor co-ordination of healthy elderly people. AB - Motor co-ordination is an important prerequisite to adequate upper-extremity performance. With the ageing of the population, more and more elderly people are at risk of acquiring upper-extremity motor inco-ordination following sensorimotor deficit. The main objective of the study was to develop normative data on upper extremity motor co-ordination for elderly people. Three hundred and sixty subjects aged 60 and over were randomly selected and evaluated with the Finger Nose Test. The results revealed a linear decline in the performance of this test with age. Younger, more active and subjectively healthier subjects presented better motor co-ordination. Some differences were found between sexes and sides. The normative data will help clinicians to identify pathological reduction in motor co-ordination in an elderly population. PMID- 7793332 TI - Relationship of health behaviours to five-year mortality in an elderly cohort. AB - To assess the risk of mortality associated with different health behaviours in a Mediterranean elderly population, we have analysed the mortality experience of a cohort of 1219 non-institutionalized men and women aged 65 years or over, who had participated in the 1986 Health Interview Survey of Barcelona. At baseline, self reported information on smoking, alcohol consumption, physical activity, and hours of daily sleep was collected through face-to-face home interviews. After 5 years of follow-up, a total of 224 (18.4%) participants had died. After adjusting for age, level of education and perceived health status, current smokers at baseline had a relative risk of dying during the follow-up of 3.0 [95% confidence interval (CI) 1.78, 5.04] compared with non-smokers. Those reporting moderate alcohol consumption had a relative risk of dying of 0.38 (95% CI 0.17, 0.86) compared with abstainers. Finally, individuals who reported a sedentary life style had a risk of dying of 1.53 (95% CI 1.08, 2.15) compared with the more active. Although limited for interpreting associations as causal relationships, our results add to the evidence that the adverse effects on survival of smoking and of being sedentary extend later into life. Because of the high prevalence of a sedentary life-style among elderly people, results suggest that promoting physical activity may have an important role in enhancing survival in this age group. PMID- 7793333 TI - The SF-36 health survey questionnaire: is it suitable for use with older adults? AB - An Anglicized version of the SF-36, a recently developed generic health status measure, was tested among people aged 65 years and over in hospital outpatient and general practice settings as both a self-completed and interview-administered instrument. The SF-36 was quick to complete, with 84% completed in 10 minutes or less (median time 8 minutes), while the distribution of scores provided further evidence of its sensitivity and validity. As an interview-administered instrument the SF-36 was acceptable among all age groups, although 32% of outpatients and 10% of general-practice patients, consisting predominantly of people aged 75 years and over with poor physical or mental health scores, felt unable to self complete the questionnaire. In addition, 26% of respondents missed out at least one of the 36 statements, with missing items being significantly related to older age and self-completion. Missing responses were mainly concentrated on a small number of questions whose emphasis on work or vigorous activities meant that they were frequently regarded as not applicable by elderly people. Suggested modifications to these questions for elderly respondents are given. With these changes the SF-36 is regarded as suitable for use as a self-completed questionnaire among the younger age group of elderly people, although some assistance may often be required by people aged 75 years and over and especially those with poor physical or mental health. PMID- 7793334 TI - A Hierarchical Assessment of Balance and Mobility. AB - The Hierarchical Assessment of Balance and Mobility (HABAM) is a new instrument which displays changes in balance and mobility graphically. To assess the validity, reliability, and responsiveness to change of the HABAM it was compared with the Barthel Index, the Spitzer Quality of Life Index, the Folstein Mini Mental Status Examination, and the Lawton-Brody Instrumental Activities of Daily Living Scale. A consecutive sample (n = 28) of patients aged 65 and older admitted to a tertiary-care teaching hospital was studied. Convergent construct validity was assessed by correlation with the Barthel Index (r = 0.76) and its mobility subscale (r = 0.74), and discriminant validity by correlation with the Folstein Mini Mental Status Exam (r = 0.15), Lawton-Brody Instrumental Activities of Daily Living (r = 0.30), and Spitzer Quality of Life Index (r = 0.39). Reliability was demonstrated by an intra-class correlation coefficient of R1 = 0.94. Responsiveness was demonstrated by a relative efficiency of 3.13 and an effect size of 0.59. The HABAM, a new instrument to assess balance and mobility in the hospitalized elderly, is valid, reliable, and responsive to change. PMID- 7793336 TI - How useful are non-random comparisons of outcomes and quality of care in purchasing hospital stroke services? AB - We performed a prospective observational study using a stroke register, case-note review and survey of carers with 6 months of follow-up in two adjacent health districts in East London. District 1 was a teaching district and had no special stroke service; District 2 had a comprehensive stroke service comprising stroke unit, review of all stroke admissions and community follow-up. Three hundred and sixty-one consecutive patients with stroke admitted to hospital and 103 carers were surveyed at 6 months from admission using the Royal College of Physicians (London) Stroke Audit standards. We also assessed mortality, disability, perceived health, mood, and satisfaction with services 6 months after stroke, carer mood, perceived health and satisfaction with services. The standard of care was below that set by the Royal College of Physicians of London in both districts and there were no significant differences between the districts in age standardized mortality at 1 and 6 months, Barthel score, extended ADL score, Geriatric Depression score, Nottingham Health Profile score and patient satisfaction with services at 6 months. Carer outcomes did not differ between districts. Service costs, particularly costs of rehabilitation services, were much lower in District 2. A comprehensive district stroke service was not associated with major differences in patient outcomes or standards of care. This may have been because the non-random nature of the comparison meant that the patients differed in other ways than in the nature of treatment. Caution is needed when using these techniques in making purchasing decisions. PMID- 7793335 TI - The nutritional status and clinical course of acute admissions to a geriatric unit. AB - Undernutrition of long-stay hospital patients and those in surgical units is well documented. This study was designed to determine the extent of the problem in elderly people admitted to hospital with acute medical problems and to assess the relationship between nutritional status and course of hospital stay. Sixty-nine patients underwent a nutritional assessment on admission and at intervals throughout their hospital stay and episodes of sepsis were documented. Severely malnourished patients were identified using body mass index, BMI (22%) and corrected arm muscle area, CAMA (26%). Episodes of sepsis occurred significantly more often in the severely undernourished group (p < 0.04). The median length of stay of the group was 16 days (range 2-113): during this time there was no significant change in markers of nutritional status apart from actual muscle circumference (AMC), which showed a reduction in measurement between admission and discharge which was statistically significant (p < 0.0003). This study indicated that severe malnutrition is common in elderly medical admissions, and that it is associated with an increased risk of sepsis. Additional nutritional depletion may occur during hospital stay, and is not easily recognized unless anthropometry is undertaken. PMID- 7793337 TI - Serum creatinine levels in older adults: relationship with health status and medications. AB - We aimed to examine the association of serum creatinine with health status and current medications in the population of older adults. We employed a cross sectional study within an ongoing cohort of 3999 residents of three communities of the Established Populations for Epidemiologic Studies of the Elderly who had venepuncture at the 6-year follow-up when they were aged 71 years and older. Serum creatinine levels, history of diabetes and heart attack, current medications, and blood pressure were measured. Creatinine levels were higher in men than in women, and in blacks than in whites. Higher creatinine levels were observed in persons with a history of diabetes or heart attack, and in those reporting use of cimetidine and diuretic medications. Persons taking frusemide and the potassium-sparing diuretics had higher creatinine levels than those taking thiazides. This study confirms associations of higher creatinine with male sex, older age, black race, history of diabetes and cimetidine use reported from cross-sectional research in younger populations and in smaller, more selected groups of older adults. Longitudinal studies will be necessary to strengthen our understanding of the causes of changes in kidney function in the older population. PMID- 7793339 TI - The use of deaf-aid communicators in a Salford Hospital: a failure of communication? AB - It is estimated that 7.5 million adults in the UK have varying degrees of hearing loss. People with hearing deficits often feel isolated, neglected and can be mistakenly labelled as confused. Responding to this need, ten deaf-aid communicators were purchased for our elderly-care wards. It however became apparent that the aids were being under-used, and to test this observation a survey of ten elderly-care wards was undertaken. Fifty-six nurses were questioned about their knowledge and use of the communicators. Only 32% knew the communicators were on their ward. Of these 32%, only 61% knew where the aids were kept and only five nurses had ever used the communicators. Only one original, functioning communicator was found and over 50% of the machines could not be recovered. The possible reasons for the failure of this initiative are discussed and lessons drawn. Similar surveys in other hospitals and general practice would be useful to determine the level of service offered to patients with hearing impairments and to provide a basis for future audit. PMID- 7793338 TI - Age-associated alterations in thirst and arginine vasopressin in response to a water or sodium load. AB - We have examined simultaneous changes in thirst, plasma osmolality and arginine vasopressin, after oral water loading or hypertonic saline infusion. The studies were carried out in the same subjects, comprising young controls aged 26.8 years (SD 4.8, n = 10) and health status-defined elderly people aged 72.1 years (SD 3.1, n = 10). Water loading caused significant falls in plasma osmolality (p < 0.001) and thirst (p < 0.001), but there was no variation with age. Infusion with 462 mmol/l of sodium chloride increased plasma osmolality significantly (p < 0.001), but there was no variation with age (p = 0.12). The perception of thirst during the osmotic loading experiment was recorded differently by the two age groups (p < 0.0001). However, linear regression analysis showed no age difference in the relationship between thirst and plasma osmolality during osmotic loading. During osmotic loading the relationship between the plasma concentration of arginine vasopressin in response to increasing plasma osmolality varied significantly (slope: p = 0.02; intercept: p = 0.02). Plasma arginine vasopressin rose more rapidly with increasing plasma osmolality in old subjects. PMID- 7793340 TI - Review: readmission of elderly patients to hospital. PMID- 7793341 TI - Geriatric day hospitals. PMID- 7793342 TI - Twenty-four-hour ambulatory blood pressure monitoring in healthy elderly people: reference values. AB - One hundred and two healthy elderly volunteers (aged 65-83 years) underwent 24 hour ambulatory blood pressure monitoring. Mean day- and night-time pressures were higher than reported for younger subjects. Removing outlying BP measurements from individual 24-hour recordings only minimally affected mean figures of the group but in some individuals mean day diastolic BP may be up to 5 mmHg lower on editing. Using unedited data, mean day and night pressures were 134/81 mmHg and 119/67 mmHg respectively (corresponding 95th centiles 160/96 mmHg and 146/84 mmHg) and systolic and diastolic BP loads were 36% and 21%. These values may be used as temporary reference values for elderly subjects pending the results of longitudinal studies. Studies quoting ABPM data should specify whether data editing has been employed and, if so, the editing thresholds should be stated. PMID- 7793343 TI - Prediction of rehabilitation after hip fracture. AB - Six hundred and forty-three consecutive patients admitted from their own home with a hip fracture were studied to determine which factors would predict patients' abilities to continue living at home. At 1 year from injury 22% of patients had died, 14% were in long-term residential care and the remaining 65% were living at home. The pre-fracture mobility of the patients was the most significant factor in predicting ability to continue to live at home, but also significant were mental state, physical health, age and type of fracture. PMID- 7793345 TI - Urologic complications of renal transplantation. PMID- 7793346 TI - The experience of the CHU Liege with conservative surgery in the management of upper urinary tract tumors. AB - A review of 20 cases of conservative surgery for urothelial tumors of the upper tract is presented. The morbidity is limited; the recurrence rate is around 15% in the ipsilateral urinary tract with a mean follow up of 41 months. Conservative surgery does not seem to carry a higher fatal risk as compared to more radical surgery. It has indications in some cases which are defined. PMID- 7793344 TI - Tetanus immunity in elderly people. AB - The aims of this study were to document the level of tetanus immunity in elderly people; to assess the value of immunization history in predicting tetanus immune status and to determine the response to tetanus immunization in elderly people compared with younger subjects. One-hundred day-hospital attenders (group 1), 100 long-term-care residents (group 2) and 50 young subjects (group 3) were recruited. Protective titres of tetanus antitoxin antibodies were detected in 20% of group 1, 45% of group 2 and 80% of group 3. Tetanus immunization history was a poor predictor of immune status in older people with a positive predictive value of 50% and a negative predictive value of 76%. The response to tetanus immunization was slower and of lower magnitude in older people. However, 36 of 37 older subjects developed protective levels of tetanus antitoxin antibodies on completion of a primary immunization programme. PMID- 7793347 TI - [Synchronous bladder metastasis of a clear-cell adenocarcinoma of the kidney]. AB - Urinary bladder synchronous metastases from renal cell carcinoma are rare, three cases were reported in the literature and we present the fourth. In these four published cases, the bladder metastases followed a left kidney tumor and in three, a brain metastases was also found. A possible retrograde metastatic dissemination through the left genital and vertebral veins has to be taken in consideration. The short survival after the extirpation of the tumor and the bladder metastases implies a less aggressive approach in the presence of a bladder metastases. PMID- 7793348 TI - Fluorescence imaging of bladder cancer. AB - Fluorescence tagging of tumors by sensitizing agents such as hematoporphyrin derivatives is an efficient method for diagnosing tumors but presents, even at low doses, a number of serious drawbacks for the patients. We demonstrate a fiberoptic instrument for the diagnosis of bladder cancer, based on a tripled frequency Nd YAG laser, without need for sensitizing agents, based on the autofluorescence of tissues. The contrast demarcation obtained for CIS and TCC respectively is 2.2 and 2.7, which is about 30% higher than what can be obtained after photosensitizing. The integration of the diagnostic method with a reliable therapeutic technique for tumor cell destruction, opens the way for cost effective preventive care of high risk patients. PMID- 7793349 TI - [Electrophysiological study of the distal motor branch of the internal pudendal nerve]. AB - The authors describe their experience with the Swash technique. It consists of the measurement of the latency over the distal segment of the motor branch of the pudendal nerve following a transrectal stimulation of the pudendal nerve during a rectal examination. The response is picked up from the anal sphincter by the use of a surface electrode and from the bulbocavernosus muscle with a needle electrode. PMID- 7793350 TI - Nocturnal penile tumescence evaluation before and after corporeal plication for Peyronie's disease. AB - A prospective study was done on 76 patients who underwent surgical correction by corporeal plication of the penile deformity secondary to Peyronie's disease. Nocturnal penile tumescence and rigidity were recorded by RigiScan during three consecutive nights, before and after the operation. A significant number of patients developed erections of better quality especially at the tip, after this corporeal plication procedure. These data indicate that corporeal plication does significantly enhance the quality of erectile episodes, by increasing penile rigidity. PMID- 7793352 TI - Complications of xanthogranulomatous pyelonephritis (XGP). PMID- 7793351 TI - A histopathological study of deep dorsal penile vein in venogenic impotence. AB - We have studied the histopathology of 87 dorsal penile veins, obtained from patients who underwent a resection of the deep dorsal penile vein because of proven venous leakage. The amount of muscle tissue and of collagenous connective tissue has been numerically quantified. Special attention has been focused on the muscular/collagenization ratio. We show that this ratio is not correlated to age neither with the outcome of the operation and that no differences exist between veins in venous leakage patients and in potent patients. This study confirms that the reduction of venous outflow-the so called corporeal veno-occlusive mechanism is probably a secondary passive phenomenon, due to smooth muscular relaxation, and mainly located within the corpora cavernosa, between the expanding sinusoidal wall and the noncompliant tunica albuginea. Our findings also strongly refute the hypothesis that polsters or other venous wall characteristics contribute to the normal physiology of the deep dorsal penile vein. PMID- 7793353 TI - Eosinophilic cystitis: a rare case which presented as an invasive bladder tumor. AB - Eosinophilic cystitis is a rare inflammatory lesion of the bladder of unknown etiology. It can be confused clinically and cytoscopically with invasive bladder cancer. We report a case in which the lesion presented as an invasive bladder tumor and we discuss the literature in brief. PMID- 7793354 TI - Recombination between genetically modified and unmodified Autographa californica nuclear polyhedrosis virus in Trichoplusia ni larvae. AB - Trichoplusia ni larvae have been injected with a mixture of wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) and a mutant derivative, AcRP8.UW1.lacZ, which lacks the polyhedrin gene, and has the p10 gene replaced by the Escherichia coli beta-galactosidase gene. Following plaque assay of the haemolymph and subsequent staining for beta-galactosidase activity and scoring for polyhedra, recombinant plaques were identified and the recombination frequency estimated as 6.6%. PMID- 7793355 TI - Genomic identification of Rickettsia slovaca among spotted fever group rickettsia isolates from Dermacentor marginatus in Armenia. AB - Restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) amplified genes was used for genomic identification of Armenian isolates of the Spotted fever group (SFG) rickettsiae with unclear taxonomic position. Analysis was performed by using one genus-specific primer pair derived from R. prowazekii citrate synthase gene and two species-specific primer pairs derived from R. rickettsii genes for 190 K and 120 K antigens following AluI, PstI and RsaI digestion of amplicons. All tested rickettsial SFG Armenian isolates from Dermacentor marginatus were identified as R. slovaca. The geographic distribution and genetic homogeneity of R. slovaca strains are discussed. PMID- 7793356 TI - Protective immunity induced by 67 K outer membrane protein of phase I Coxiella burnetii in mice and guinea pigs. AB - A 67 K outer membrane protein (OMP) isolated from phase I Coxiella burnetii QiYi strain was purified with monoclonal antibodies (MoAb) coupled to CNBr-Sepharose 4B. Chemical analyses of the 67 K protein showed that it contained seventeen kinds of amino acids and no LPS. The immunogenicity and protectivity of the 67 K protein against C. burnetii was evaluated in mice and guinea pigs by in vitro lymphocyte proliferation assay, delayed-type skin test, antibody conversion rate, and immunization and challenge tests. Intraperitoneal injection of the 67 K protein resulted in antibody production against phase I and II whole cell antigens. The anti-67 K antibody conversion rate was found to be 100% in mice and guinea pigs as well. Lymphocytes were responses in vitro to specific antigen. In addition, delayed-type hypersensitivity appeared two weeks after immunization with the 67 K protein. Moreover, 100% of mice and guinea pigs inoculated with the 67 K protein were protected against a challenge with 10(3) ID50 virulent C. burnetii. In conclusion, these results demonstrate that the 67 K OMP elicits in vivo and in vitro both B cell-mediated and T cell-mediated immunity in mice and guinea pigs. Thus the 67 K protein is a candidate for an effective subunit vaccine against Q fever. PMID- 7793357 TI - Increased yields of Japanese encephalitis virus in heat shocked cell cultures. AB - Monolayers of porcine stable kidney (PS) and baby hamster kidney (BHK-21) cell lines were exposed to 43 degrees C and 41 degrees C, respectively, for 4 hrs and infected with Japanese encephalitis virus (JEV) Nakayama strain at low and high multiplicity of infection. Virus yields were increased by 0.2-2.5 log PFU/ml in heat shocked cultures compared to control cultures at 37 degrees C. This phenomenon was detected in the late phase of replication after 16 hrs post infection. The progeny virus obtained from heat shocked cultures was more thermostable. PMID- 7793358 TI - Immunogenicity of Coxiella burnetii whole cells and their outer membrane components. AB - The immunogenicity and protective efficacy of the phase I and phase II Coxiella burnetii whole cells (Cb I and Cb II) and their outer membrane components (OMC), i.e. phase I trichloroacetic acid extract (TCAE), phase I 29 K protein (PRO), phase I and II lipopolysaccharides (LPS I, LPS II), polysaccharides (PS I, PS II), and lipid A (LA I, LA II), were compared. The highest immune response was observed in BALB/c mice by Cb I in both humoral immunity and lymphocyte transformation assays, and in the protective effect as well. The immune response was also significant by Cb II, but their protective capacity was low. The OMC reacted variously. Only TCAE and PRO gave a high value of humoral immunity evaluated by the serological methods. All OMC reacted in the haemolytic plaque assay giving different responses. Lymphoproliferation of splenocytes was positive with all OMC using both Cb I and Cb II antigens with the exception of PS I and PS II in the case of Cb II antigen. The induction of protection against infectious Cb I was demonstrated after immunization with TCAE, PRO, and LPS I. Other OMC did not induce protection against this agent. PMID- 7793359 TI - Human type I interferons: structure and function. AB - Human type I interferons (IFNs) comprise a family of 13 IFN-alpha subtypes and single species of IFN-beta and IFN-omega. Their 20% overall sequence homology determines identical secondary and tertiary folding of polypeptides. Three dimensional models suggest that the globular structure of type I IFNs consists of a bundle of 5 alpha-helices, which might form two polypeptide domains. Disulfide bond Cys 29-Cys 139 stabilizes both domains in a bioactive configuration. The IFN molecule exerts its functional entity only as an organic polypeptide complex and therefore molecular fragments apparently lack biological activity. IFN-beta, IFN omega and some IFN-alpha subtypes are glycoproteins, but the sugar moiety was found to be neither structurally nor functionally relevant. Type I IFNs share a common cellular receptor, a fact that implies a high structural conservativity of their receptor-binding areas. Two conservative hydrophilic regions associated with the amino acids (aa) 30-41 and 120-145 appear to constitute the basic framework of receptor recognition site in type I IFNs. However, the individual IFN-(sub)types induce different spectra of biological effects which reflect some specificity in modelling of binding sites. Besides a subtle sequential heterogeneity in the segments aa 30-41 and 120-145, also the variable hydrophilic aa regions 23-26, 68-85 and 112-121 are responsible for structural and functional individuality among human type I IFNs. The interaction between IFN and its receptor seems to be a complex event which triggers simultaneously antiviral, antiproliferative and immunomodulating actions, although different parts of IFN molecule are not involved equally in eliciting of respective basal activities. PMID- 7793360 TI - Perinatal asphyxia: MR findings in the first 10 days. AB - PURPOSE: To determine whether one can detect hypoxic-ischemic brain injury by MR in the first 10 days of life and to identify patterns of injury in affected neonates. METHODS: Standard T1- and T2-weighted MR sequences that were performed in the first 10 days of life in 20 patients who suffered hypoxia/ischemia in the intrapartum or neonatal periods were reviewed retrospectively. Images were evaluated for patterns of signal changes. RESULTS: Four patients had normal findings and were clinically healthy. The remaining 16 patients were divided into four groups based on pattern of injury: (a) primarily deep gray matter involvement; (b) primarily cortical involvement; (c) primarily periventricular white matter injury; and (d) mixed injury pattern. Two patients had appearances that suggested prepartum injury. T1 shortening was seen in injured tissue as early as 3 days after injury. T2 shortening did not appear until 6 or 7 days after injury. CONCLUSION: MR can show brain damage in asphyxiated neonates during the first 10 days of life and shows early appearances of several patterns of brain injury. PMID- 7793361 TI - Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: imaging and pathology findings. AB - PURPOSE: To investigate the imaging and pathologic characteristics of acute encephalopathy with bilateral thalamotegmental involvement in infants and children. METHODS: Five Japanese children ranging in age from 11 to 29 months were studied. We performed CT imaging in all patients, 10 MR examinations in four patients, and an autopsy in one patient. RESULTS: The encephalopathy affected the thalami, brain stem tegmenta, and cerebral and cerebellar white matter. The brain of the autopsied case showed fresh necrosis and brain edema without inflammatory cell infiltration. Petechiae and congestion were demonstrated mainly in the thalamus. CT and MR images showed symmetric focal lesions in the same areas in the early phase. These lesions became more demarcated and smaller in the intermediate phase. The ventricles and cortical sulci enlarged. MR images demonstrated T1 shortening in the thalami. The prognosis was generally poor; one patient died, three patients were left with severe sequelae, and only one patient improved. CONCLUSIONS: The encephalopathy might be a postviral or postinfectious brain disorder. T1 shortening in the thalami indicated the presence of petechiae. PMID- 7793363 TI - Holoprosencephaly: an analysis of callosal formation and its relation to development of the interhemispheric fissure. AB - PURPOSE: To correlate the degree of hemispheric fusion in holoprosencephaly with degree of callosal formation, with degree of thalamic and basal ganglia fusion, and with presence or absence of dorsal cyst. METHODS: MR, CT, and ultrasonography from 19 patients with holoprosencephaly was retrospectively reviewed. The imaging studies were graded according to extent of the hemispheric fusion, thalamic fusion, corpus striatum fusion, callosal formation, and the presence or absence of a dorsal cyst. These factors were statistically correlated with each other using Kendall rank correlation coefficient. RESULTS: There were significant correlations between hemispheric fusion and failure of corpus callosum formation, presence of dorsal cyst and failure of corpus callosum formation, and hemispheric fusion and presence of dorsal cyst. Additional correlations were noted between thalamic fusion and corpus striatum fusion. CONCLUSIONS: Our results suggest that the presence of an interhemispheric fissure is necessary for callosal formation, and the presence of a dorsal cyst may interfere with callosal formation in holoprosencephaly. PMID- 7793362 TI - Postvaricella basal ganglia infarction in children. AB - Two patients presented with acute neurologic deficits attributable to contralateral basal ganglia infarction 1 to 3 months after episodes of chickenpox. Both presented with hemiparesis with one patient also demonstrating ipsilateral choreoathetosis. In both patients MR revealed unilateral basal ganglia infarction. Cerebral angiography findings in one patient were normal; in the second, there was unilateral narrowing of the common carotid artery and of proximal branches of the anterior and middle cerebral artery. PMID- 7793364 TI - Hematopoietic marrow regeneration in pediatric patients undergoing spinal irradiation: MR depiction. AB - PURPOSE: To evaluate changes in vertebral marrow signal intensity that occur over time in children undergoing craniospinal radiation therapy, specifically evaluating for the occurrence and timing of marrow regeneration. METHODS: MR images of nine pediatric patients (ages 4 to 12 years) with posterior fossa medulloblastoma who received total spinal irradiation (24 to 40 Gy) and had at least three MR examinations were reviewed. Signal intensity to vertebral body marrow was graded by two pediatric neuroradiologists who were blinded to patient identity and to the timing of the studies. RESULTS: Eight of nine patients demonstrated increasing signal intensity of the vertebral marrow after irradiation, consistent with conversion of hematopoietic to fatty marrow. In each of these patients, this was followed by subsequent decreasing signal intensity in a mottled or peripheral band pattern indicating recovery of hematopoietic marrow. CONCLUSION: Changes in vertebral body signal intensity consistent with marrow reconversion commonly are seen in pediatric patients 11 to 30 months after they undergo total spinal irradiation. PMID- 7793365 TI - Ultrasound determination of the normal location of the conus medullaris in neonates. AB - PURPOSE: To establish the normal range of the position of the conus medullaris in neonates and determine whether it differs from that in adults. METHODS: One hundred five healthy neonates born over an 18-day period in a single obstetric unit had ultrasound examinations of their lower spines to relate the conus medullaris to the nearest intervertebral disk or midvertebral level. RESULTS: The mean position of the conus was midway between the L1-2 disk and mid-L-2 body, ranging from T-12/L-1 to L-3, with the modal position being L1-2 (47.6%). A small but significant rise in position from 33 to 42 weeks postconceptual age was identified. Comparison with data previously reported from adults showed a small but highly significant difference in conus position of approximately 0.25 vertebral levels. DISCUSSION: Our data confirm studies suggesting that ascent of the cord after birth is minor. PMID- 7793366 TI - Ethmoid mucocele in an infant with a benign fibroosseous lesion. AB - We present a case of ethmoid mucocele occurring in a two-month-old child, and associated (presumably causally) with a benign fibroosseous lesion of the ethmoid bone. These two conditions may be more frequently associated than previously recognized; MR greatly facilitates their evaluation. PMID- 7793367 TI - Solitary infantile myofibromatosis of the skull. AB - We describe the CT and plain-film appearance of solitary infantile myofibromatosis of the skull in a 5-year-old boy. This benign lesion closely resembles histiocytosis X on imaging studies. PMID- 7793368 TI - Occlusion of cerebral arteriovenous malformations with N-butyl cyano-acrylate is permanent. AB - PURPOSE: To verify the permanence of total occlusion of cerebral arteriovenous malformations after embolization with N-butyl cyano-acrylate and to evaluate the occlusion rate. METHODS: One hundred thirty-four patients were treated for cerebral arteriovenous malformations with N-butyl cyano-acrylate embolization after superselective catheterization. Those initially totally occluded have been followed with angiography. RESULTS: In 15 instances (11.2%) the arteriovenous malformations were totally occluded by embolization alone. Follow-up angiograms have been performed in 12 cases (80%) after 4 to 78 (mean, 27) months after embolization. In all instances the arteriovenous malformations have remained occluded, and there have been no clinical signs of activity. CONCLUSION: After total occlusion of a cerebral arteriovenous malformation with N-butyl cyano acrylate, the lesion stays occluded, and the clinical course seems stable. PMID- 7793369 TI - Iatrogenic carotid-cavernous fistula occurring after embolization of a cavernous sinus meningioma. AB - A carotid-cavernous fistula developed in a 62-year-old woman during an attempt at embolization of a skull base meningioma. The cause is thought to be perforation by the guide wire during catheterization of the meningohypophyseal trunk at the sharp bend at its origin. PMID- 7793370 TI - Adolf Bingel, the second inventor of lumbar pneumencephalography. PMID- 7793371 TI - Clinically unsuspected venous malformations limited to the submandibular triangle: CT findings. AB - PURPOSE: To present the CT characteristics of histologically confirmed venous vascular malformations limited to the submandibular triangle in patients without clinical stigmata of venous vascular malformations. METHODS: The clinical records and CT scans of five women with venous vascular malformations limited to the submandibular triangle were reviewed. Patients ranged from 39 to 70 years of age. None of the patients had a history of malignant tumors. All patients presented with a solitary suprahyoid neck mass. None of the patients demonstrated cutaneous manifestations of venous vascular malformation. RESULTS: Contrast-enhanced CT scans in all five patients demonstrated a lobulated, heterogeneously enhancing, well-circumscribed solid mass, separable from the submandibular gland. Areas of contrast enhancement within each mass were isodense to the internal jugular vein in four of five cases. Only two of five lesions demonstrated focal calcifications. Excisional biopsy (two patients) demonstrated pathologic features compatible with venous vascular malformation. Fine needle aspirations (three patients) yielded venous blood or blood-tinged fluid. CONCLUSIONS: Venous vascular malformations may present as isolated neck masses in adults without typical clinical stigmata. Clues to the CT diagnosis include a lobulated appearance to the mass with intense but heterogeneous contrast enhancement. This appearance, in combination with results of fine needle aspiration, may be sufficiently diagnostic to preclude excisional biopsy. PMID- 7793372 TI - A reappraisal of the radiologic findings of acute inflammation of the epiglottis and supraglottic structures in adults. AB - PURPOSE: To evaluate the radiologic characteristic of acute inflammation of the epiglottis and supraglottic structures in adults. METHODS: The clinical and radiographic findings in 27 adult patients with epiglottitis (average age, 43 years; range, 28 to 81 years) were compared with those of a control group of asymptomatic subjects (n = 15; average age, 48 years; range, 24 to 79 years). Unusual clinical aspects in the current series included two patients who were positive for human immunodeficiency virus, 1 with acquired immunodeficiency syndrome and Kaposi sarcoma, 3 with emphysematous epiglottitis, 1 with abscess formation, and 1 with laryngeal carcinoma. One patient required emergency tracheostomy. One patient died of pneumonia. RESULTS: The ratio of the soft tissue parameters to the anteroposterior width of the C-4 vertebral body yielded three key parameters of high statistical significance in adult epiglottitis. The ratio of the width of the epiglottis to the anteroposterior width of C-4 should not be greater than 0.33 (sensitivity, 96%; specificity, 100%). The ratio of the prevertebral soft tissue to C-4 should not exceed 0.5 (sensitivity, 37%; specificity, 100%) and the ratio of the width of the hypopharyngeal airway to the width of C-4 should be less than 1.5 (sensitivity, 44%; specificity, 87%). The aryepiglottic folds were enlarged in 85%, and the arytenoids were swollen in 70% of the patient population (specificity, 100%). CONCLUSION: These defined radiologic parameters should aid in the diagnosis of acute epiglottitis in adults. PMID- 7793373 TI - MR in neurofibromatosis of the larynx. AB - We report the MR results of four patients with plexiform neurofibromas of the larynx. Three had irregular margins and were circumferential around the airway. The distinction between regularly and irregularly shaped neurofibromas may have implications for symptom onset. PMID- 7793374 TI - MR findings of sclerosing cervicitis. AB - The MR appearance of sclerosing cervicitis in the case presented is that of a fusiform mass arising in the lateral neck with vascular encasement. The mass is mildly hyperintense to skeletal muscle on the T1- and T2-weighted images. PMID- 7793375 TI - Clinical significance of asymmetry of the fornix and mamillary body on MR in hippocampal sclerosis. AB - PURPOSE: To investigate the clinical significance of MR-defined asymmetry of the fornix and mamillary body for presurgical determination of the side of hippocampal sclerosis in patients with temporal lobe epilepsy. METHODS: Fast spin echo MR images were evaluated for evidence of an asymmetrically small fornix and mamillary body in 33 patients with pathologically proved hippocampal sclerosis (presurgical hippocampal sclerosis group), 7 patients who had undergone anterior temporal lobectomy (mean, 3 years from surgery) because of hippocampal sclerosis (postsurgical hippocampal sclerosis group), and 34 healthy subjects (control group). Fast spin-echo hippocampal volumetry was performed in each patient. RESULTS: In the control group, 6% (2 of 34) of subjects had MR evidence of asymmetrically small fornix and none (0 of 34) of the subjects had asymmetrically small mamillary body. In the patient population, an asymmetrically small fornix was seen in 42% of presurgical hippocampal sclerosis group, 39% (13 of 33) ipsilateral, and 3% (1 of 33) contralateral, and in 71% of the postsurgical hippocampal sclerosis group (5 of 7), all ipsilateral. In the presurgical hippocampal sclerosis group, hippocampal atrophy measured with MR was more severe in patients with an ipsilaterally small fornix than in patients without. An asymmetrically small mamillary body was found ipsilaterally in 3% (1 of 33) of the presurgical hippocampal sclerosis group and in 57% (4 of 7) of the postsurgical hippocampal sclerosis group; all patients with an asymmetrically small mamillary body in the postsurgical hippocampal sclerosis group also had an asymmetrically small fornix on the same side. CONCLUSION: In presurgical hippocampal sclerosis patients, an asymmetrically small fornix can be seen ipsilaterally on the side of the hippocampal sclerosis; however, its low frequency, its association with severe hippocampal atrophy only, and the possibility of false-positive results limit its clinical usefulness in determining the side of the seizure focus. An asymmetrically small mamillary body is too rare to be used for presurgical location of hippocampal sclerosis. However, an asymmetrically small fornix and mamillary body are frequently seen on MR images after temporal lobectomy. PMID- 7793376 TI - The asymmetric mamillary body: association with medial temporal lobe disease demonstrated with MR. AB - PURPOSE: To determine whether mamillary body atrophy is caused by deafferentation of the mamillary body in patients with mesial temporal sclerosis. METHODS: We studied 36 patients with thin-section MR to assess mamillary body symmetry. These patients included 10 control subjects without seizures and 26 patients with a history of seizures. Thin-section T1 scans were available for all cases. The patients with epilepsy underwent axial and coronal T2 scans as well. RESULTS: In five of eight cases with prior medial temporal lobe resection for intractable epilepsy, there was evidence of unilateral mamillary body atrophy ipsilateral to the resection. Similar findings were evident in three of six patients with MR findings of mesial temporal sclerosis without surgery. Two patients with medial temporal stroke or tumor also had ipsilateral mamillary body atrophy. CONCLUSION: These findings provide support for the proposed mechanism of mamillary body atrophy caused by prior medial temporal lobe injury. PMID- 7793377 TI - MR in temporal lobe epilepsy: early childhood onset versus later onset. AB - PURPOSE: To study the relationship between the MR findings and the clinical features in temporal lobe epilepsy in childhood (less than 10 years of age). METHODS: MR studies were performed with a 1.5-T imager on 38 temporal lobe epilepsy patients receiving drug therapy at the psychiatric department. These patients were divided into two groups according to their age at onset (10 years or less, 11 years or more). The two groups were compared in terms of the MR findings and clinical features. RESULTS: The 11 younger-onset patients included 5 with a high-signal area attributed to mesial temporal sclerosis. Clinically, all of these 5 patients had a history of "complex" febrile convulsions, which sharply distinguished them from the older-onset group. CONCLUSION: The analysis suggests that complex febrile convulsions in infancy can be associated with high-signal areas on MR attributed to mesial temporal sclerosis. PMID- 7793378 TI - Size estimation and magnification error in radiographic imaging: implications for classification of arteriovenous malformations. AB - PURPOSE: To assess magnification error in digital subtraction angiography as it pertains to arteriovenous malformation (AVM) size. METHODS: A rectangular grid phantom with equally spaced markers mounted in a stereotactic frame was imaged with digital angiographic equipment. The location and orientation of the grid was altered relative to the central plane of the phantom. Both linear and area measurements were made according to the perceived location of phantom markers using a standard catheter calibration technique and compared with stereotactically derived estimates. Finally, a single case example of an angiographically imaged rolandic AVM was used to compare linear dimensions obtained with both described techniques. RESULTS: The determination of location and size with standard angiographic imaging is subject to error because of the divergent geometry of the incident x-ray beam. The resulting nonconstant geometric magnification causes errors in linear measurements of 10% to 13% at depths of 7 cm from the calibration plane. Errors in area measurements at the same position increase by 20% to 25%. Measurements of maximum diameter or cross sectional area may have an additional error when nonspherical objects are inclined to the viewing direction (40% at 45 degrees inclination). These errors are reduced to less than 1 mm using the stereotactic technique. Some commercial angiographic systems have internal software to enable a spatial calibration based on known distances in the image or on the diameter of a catheter. The catheter technique was accurate in the calibration direction (perpendicular to the catheter axis) but had a 12% error in the direction parallel to the catheter because of a nonunity aspect ratio in the video system. Measurement of the dimensions of a rolandic AVM using the catheter calibration technique had an error that ranged from -3% to +26% (standard error, 20%) with respect to the stereotactic technique. CONCLUSIONS: Numerous nonstereotactic referential systems for determining linear distances are inherently erroneous by varying degrees compared with the stereotactic technique. Area and volume determinations naturally increase this error further. To the extent that no standardized method for determining linear distances exists, significant variations in estimation of AVM size result. Classification schemes for AVMs have been hampered by this technical error. PMID- 7793379 TI - Rerupture of cerebral aneurysms during angiography. AB - PURPOSE: To assess the incidence of angiography-related rerupture of intracranial aneurysms and to analyze other risk factors of this complication. METHODS: Clinical data from 144 patients with acute subarachnoid hemorrhage from ruptured intracranial aneurysm were reviewed retrospectively. In all patients, angiography was done by the transaortic approach. RESULTS: The incidence of rerupture caused by angiography was 2 (1.4%) of 144 and that of spontaneous rerupture was 14 (9.7%) of 144. Angiography within 6 hours after the initial subarachnoid hemorrhage attack was associated with a significantly higher incidence of rerupture (4.8%) than that after a longer interval (0%). In cases of spontaneous rerupture, patients with worse levels of consciousness showed a higher incidence of rerupture, and this tendency also was evident in cases of induced rerupture. There was no significant correlation between the rerupture rate and the injection volume of contrast medium, aneurysm location, or patient age or sex. CONCLUSION: Although angiography within 6 hours after initial intracranial aneurysm rupture was associated with a higher rate of rerupture, the incidence of rerupture in this study (4.8%) was much lower than those reported previously (20% to 38.5%). The present findings suggest that emergency angiography within 6 hours after aneurysm rupture, which enables neurosurgeons to carry out early surgery, should not be discouraged. PMID- 7793380 TI - MR and cognitive testing of patients undergoing osmotic blood-brain barrier disruption with intraarterial chemotherapy. AB - PURPOSE: To determine whether osmotic blood-brain barrier disruption is associated with MR abnormalities or cognitive deterioration and, if so, whether the MR findings correlate with cognitive test results. METHODS: Fifteen brain tumor patients who had a complete tumor response (nine central nervous system lymphoma, three germ cell and two astrocytoma, and one primitive neuroectodermal tumor) treated with blood-brain barrier disruption procedures (318 total procedures) with intraarterial chemotherapy were included. MR images were evaluated for the development of white matter hyperintensity, vascular lesions, or atrophy. Cognitive testing was performed to assess deterioration caused by this therapy. RESULTS: In two patients white matter hyperintensity developed, in two small vascular lesions developed, and in one mild atrophy developed. One infarct was asymptomatic and the second one resulted in mild dysesthesia in one upper extremity. No patient showed diminished cognitive function on the posttherapy evaluation. CONCLUSION: In patients undergoing blood-brain barrier disruption with intraarterial chemotherapy, new abnormalities on MR imaging may develop. These patients maintain the same level of cognitive and neurologic function and MR findings do not correlate with the results of cognitive testing. PMID- 7793381 TI - MR of cerebral aspergillosis in patients who have had bone marrow transplantation. AB - PURPOSE: To assess the CT and MR appearance of cerebral aspergillosis in patients who have undergone bone marrow transplantation. METHODS: The imaging and clinical data of five patients with cerebral aspergillosis were reviewed retrospectively and compared with autopsy findings. RESULTS: Lesions are often located in the basal ganglia and demonstrate an intermediate signal intensity within surrounding high-signal areas on long-repetition-time MR scans. The lesions were multiple in four of the five patients and more numerous on MR images than on CT scans. The lesions (which demonstrate no parenchymal enhancement) are consistent with acute infarcts as confirmed at autopsy. In the large lesions, there is early intravascular and meningeal enhancement, as expected in acute infarcts involving an appreciable portion of the territory of a cerebral artery. CONCLUSION: The diagnosis of early cerebral infarction in a patient considered at risk for invasive aspergillosis, even without overt pulmonary disease, is an indication to institute aggressive antifungal therapy. PMID- 7793382 TI - Vascular reserve in chronic cerebral ischemia measured by the acetazolamide challenge test: comparison with positron emission tomography. AB - PURPOSE: To determine the value of the acetazolamide challenge test with stable xenon-enhanced CT (Xe CT) for making therapeutic decisions in patients with chronic cerebrovascular disease. METHODS: We compared the Xe CT-measured acetazolamide response with various measures obtained by positron emission tomography. We performed both a positron emission tomographic scan and a Xe CT study in 11 patients with chronic cerebral ischemic diseases within a 1-week interval. An increase of cerebral blood flow after injection of acetazolamide was expressed as delta AT. Regional cerebral blood flow, cerebral oxygen metabolism, oxygen extraction fraction, and cerebral blood volume were measured with oxygen 15-labeled gases by positron emission tomography. RESULTS: In low-cerebral blood flow regions, decreased delta AT was accompanied by a significant elevation of oxygen extraction fraction and cerebral blood volume, compared with oxygen extraction fraction and cerebral blood volume in regions of normal delta AT. Plotting of regional data indicated that delta was significantly dependent on oxygen extraction fraction and cerebral blood volume. The area of decreased vascular reserve determined by the Xe CT image corresponded to the area of "misery perfusion" determined by positron emission tomography. CONCLUSION: The acetazolamide challenge test with Xe CT may offer an alternative to positron emission tomography in detecting lesions with elevated oxygen extraction fraction and cerebral blood volume (misery perfusion) that result from chronic hemodynamic stress. PMID- 7793383 TI - The value of MR in differentiating subligamentous from supraligamentous lumbar disk herniations. AB - PURPOSE: To determine the value of MR criteria in differentiating subligamentous from supraligamentous lumbar disk herniations. METHODS: A retrospective review of surgical reports and MR images of 50 patients undergoing first-time lumbar surgery was performed. Three MR imaging criteria were assessed: the presence and integrity of a low-signal-intensity line posterior to the disk herniation, the size of the disk herniation in comparison with the size of the spinal canal, and the presence of disk fragments. Correlation was made with surgical findings to determine the value of these MR criteria in differentiating subligamentous from supraligamentous disk herniations. RESULTS: For determining subligamentous disk herniations: the presence of a continuous low-signal-intensity line posterior to the disk herniation was 29% sensitive, 65% specific, and 42% accurate; disk herniation size less than 50% of the size of the spinal canal was 64% sensitive, 47% specific, and 58% accurate; and the absence of disk fragments was 88% sensitive, 12% specific, and 62% accurate. Combinations of individual MR criteria did not improve diagnostic accuracy. CONCLUSIONS: For differentiating subligamentous from supraligamentous lumbar disk herniations, none of the MR imaging criteria assessed was reliable. PMID- 7793384 TI - MR imaging in a case of postvaccination myelitis. AB - We describe a case of acute transverse myelitis after the administration of the recombinant form of hepatitis B vaccine. Abnormal enhancement of MR imaging accompanied residual neurologic deficit. PMID- 7793385 TI - Posterior fossa glioblastoma multiforme: MR findings. AB - PURPOSE: To characterize the MR findings of glioblastoma multiforme in the posterior fossa. METHODS: MR studies of nine patients with surgically proved posterior fossa glioblastoma multiforme were retrospectively evaluated. MR characteristics studied included tumor location, signal intensity, enhancement pattern, and presence of intratumoral hemorrhage, as well as presence of secondary hydrocephalus or metastatic spread. RESULTS: The tumors were located in the median portion of the cerebellum or brain stem in eight cases. Six extended into the fourth ventricle. Hydrocephalus was seen in four cases. Six cases demonstrated decreased T1- and increased T2-weighted signal intensities. Three cases demonstrated mixed signal intensities suggesting intratumoral hemorrhage. All of the eight patients who received contrast showed moderate to marked heterogeneous ringlike enhancement suggesting intratumoral necrosis. Multicentric/multifocal lesions or extraaxial metastases were identified in three of the nine cases, and there was extracranial extension into the cervical region in one case. CONCLUSION: Glioblastoma multiforme is a rare tumor in the posterior fossa. Differentiating it from metastatic tumor or malignant astrocytoma was difficult. However, combination of heterogeneous and ringlike enhancement, midline location, poorly defined margin, tumoral hemorrhage, concomitant multicentric/multifocal lesions, and extraaxial or extracranial metastasis may be clues for the prospective diagnosis of glioblastoma multiforme. PMID- 7793386 TI - Transorbital color Doppler flow imaging of the carotid siphon and major arteries at the base of the brain. AB - PURPOSE: To describe and evaluate an application of sonography, transorbital color Doppler flow imaging of the carotid siphon and major intracranial arteries, and to compare it with transtemporal color Doppler flow imaging. METHODS: The carotid siphon and major arteries at the base of the brain of 50 healthy volunteers were screened using the transorbital color Doppler flow sonography. These arteries were also studied by a transtemporal approach for comparison. In 5 volunteers, MR images in special inclination planes were obtained and compared with the transorbital color-coded Doppler flow images. RESULTS: The B-mode image of the orbit and intracranial anatomic structures, in addition to the color-coded flow images, provided an unambiguous identification of the carotid siphon and major intracranial arteries. The failure rate was lower when using the transorbital approach than when using the transtemporal approach in identifying the anterior cerebral artery (17% versus 32%). Color Doppler flow imaging using the transtemporal approach was better for the middle cerebral artery, whereas color Doppler flow imaging using the transorbital approach was better for the anterior cerebral artery (contralateral). The Doppler incident angles using the transorbital approach were better for the carotid siphon and anterior cerebral artery (contralateral). CONCLUSION: Transorbital color Doppler flow imaging, when used in conjunction with the transtemporal examination, can add information concerning the major arteries at the base of the brain. PMID- 7793387 TI - A simple CT method for location of auditory brain stem implant electrodes. AB - A method for locating auditory brain stem implant electrodes that have been placed in the lateral recess of the fourth ventricle is described. CT bone window images are "inverted" to black on white, then manually superimposed onto soft tissue window images to enable identification of electrodes in relation to soft tissue structures. PMID- 7793388 TI - MR of parenchymal neurocutaneous melanosis. AB - Two cases of neurocutaneous melanosis are presented. MR showed hyperintense areas in the brain on short-repetition-time/short-echo-time sequences, compatible with intraparenchymal melanin deposits. No leptomeningeal abnormality was seen. PMID- 7793389 TI - MR lesion enhancement: spin-echo versus gradient-echo. PMID- 7793390 TI - Guglielmi coils in ruptured aneurysms. PMID- 7793391 TI - Subthalamus versus substantia nigra. PMID- 7793392 TI - Annotated bibliography. PMID- 7793393 TI - Clinical characteristics and mortality of patients screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. AB - In mortality studies of patients after acute myocardial infarction (AMI), exclusion of patients during selection from the screened population may be important for evaluating the impact of trials, but data on patients excluded from studies are rarely presented. In the Trandolapril Cardiac Evaluation (TRACE) trial of the angiotensin-converting enzyme inhibitor trandolapril versus placebo in patients with left ventricular (LV) systolic dysfunction shortly after AMI, medical history, infarct complication, and survival were accounted for in all patients screened for entry. A total of 7,001 consecutive enzyme-confirmed AMIs were screened for entry in 27 Danish coronary care units. The 1-year mortality of all screened AMI cases was 23% (95% confidence interval 22% to 24%). The target population of the TRACE trial were patients with LV systolic dysfunction (echocardiographically determined wall motion index < or = 1.2, n = 2,606 within 6 days of AMI. The 1-year mortality of this group was 34 +/- 2%. Patients with wall motion index > 1.2 (n = 3,920) had a 1-year mortality of 12 +/- 1%. were excluded. A total of 1,749 were included in the study. The excluded and included groups had a 1-year mortality of 54 +/- 3% and 24 +/- 2%, respectively. The result of the TRACE study will be applicable to two thirds of the patients with LV systolic dysfunction; however, even with this high figure, care should be taken in extrapolating the result to the general population with reduced LV function after AMI since the group excluded from the study had a higher mortality than those who were included. PMID- 7793394 TI - Doppler-derived gradients in normally functioning Monostrut Bjork-Shiley prostheses. AB - In summary, reference values of Doppler gradients obtained in a large number of patients with normal-functioning mitral and aortic Monostrut Bjork-Shiley prostheses are reported. It is shown that the value of the transprosthetic gradient increases with decreasing valve size in patients with aortic prostheses. No individual significant variations of the transprothetic Doppler gradient during a 3-year follow-up were observed. PMID- 7793395 TI - Recurrence of a discrete subaortic membrane 27 years after operative resection. PMID- 7793396 TI - Q-wave regression unrelated to patency of infarct-related artery or left ventricular ejection fraction or volume after anterior wall acute myocardial infarction treated with or without reperfusion therapy. AB - We examined the relation of Q-wave regression to left ventricular (LV) indexes in acute anterior wall myocardial infarction (AMI) in relation to reperfusion therapy. A total of 94 patients with their first anterior wall AMI (segment 6 or 7 occlusion according to the American Heart Association classification) were examined. The follow-up period with 12-lead electrocardiograms ranged from 6 to 60 months (mean 24 +/- 18). An abnormal Q wave was defined as > 40 ms and > 25% of the R-wave amplitude. Q-wave regression was defined as Q-wave disappearance and r-wave regression > 0.1 mV in > or = 1 lead. Contingency tables with the chi square test and analysis of variance were used for assessment of the relation between Q-wave regression and angiographic and clinical indexes. Q-wave regression in > or = 1 lead was found in 77% of the patients. The incidence of Q wave regression in patients with patent infarct-related artery (81%) was not significantly different from that in those with an occluded lesion (67%). Q-wave regression appeared within 1 month in 60% of patients with a patent infarct related artery but in 25% of those with an occluded lesion. No difference in the incidence of Q-wave regression was seen between patients with lesions at segments 6 (81%) and 7 (70%), or between those with (75%) and without (77%) collateral circulation. Q-wave regression did not correlate with LV ejection fraction, LV end-diastolic or end-systolic volumes, or regional wall motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793397 TI - Can atherosclerotic coronary arteries vasodilate? An intraoperative high frequency epicardial echocardiographic study. AB - Our purpose was to evaluate the vasodilating responses of atherosclerotic coronary arteries using intraoperative high-frequency (12 MHz) epicardial echocardiography. We obtained continuous high-frequency epicardial echocardiographic recordings during surgery, and determined cross-sectional lumen area from 17 coronary arterial segments (12 patients). Nitroglycerin (100 to 400 micrograms/min) was administered intravenously to reduce mean (+/- SEM) arterial pressure 14 +/- 1.8 mm Hg. The cross-sectional arterial images were classified using 3 different parameters: arterial lumen area, percentage of the arterial wall circumference that was atherosclerotic (wall thickness > 0.7 mm), and presence of an eccentrically shaped arterial lumen (maximal/minimal luminal diameter > 1.5). Nine arterial segments had small (< 5.0 mm2) arterial lumens (1.7 +/- 0.40 mm2 [+/- SEM; range 0.6 to 3.9]). With nitroglycerin, the luminal area increased 0.8 +/- 0.28 mm2 (range 0 to 2.5), and 39 +/- 12.1% (range 0 to 117). The remaining 8 segments had larger (> 5.0 mm2) lumens (8.7 +/- 0.91 mm2 [range 5.0 to 11.9]). With nitroglycerin the luminal area increased 4.3 +/- 1.11 mm2 (range 1.4 to 11.4), and 51 +/- 10.2% (range 16 to 96). Seven arterial segments had eccentric lumens; mean maximal/minimal ratio was 1.8 +/- 0.08 (range 1.6 to 2.0). The area increased 39 +/- 7.3% (range 16 to 71) with nitroglycerin. In the 10 concentrically shaped lumens (maximal/minimal lumen diameters 1.3 +/- 0.04 [range 1.1 to 1.5]), nitroglycerin increased luminal area by 48 +/- 12.6% (range 0 to 117) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793398 TI - Mechanisms of hypotension during dobutamine stress echocardiography in patients with coronary artery disease. AB - Fifty-nine consecutive patients with angiographically documented coronary artery disease were prospectively studied during dobutamine stress echocardiography. Twelve patients (20%) developed hypotension, defined as a decrease in systolic blood pressure of > or = 20 mm Hg compared with baseline. The transmitral flow velocities, isovolumic relaxation time (IVRT), and flow in the left ventricular (LV) outflow tract were measured at baseline, at maximal dobutamine dose, or during a hypotensive episode; stroke volume, cardiac output, and systemic vascular resistance (SVR) were computed. Correlates of hypotensive response to dobutamine stress echocardiography included therapy with angiotensin-converting enzyme inhibitors (p = 0.032), a longer IVRT at baseline (121 +/- 25 vs 103 +/- 28 ms, p = 0.047), a greater decrease in LV end-diastolic (-6.0 +/- 3.1 vs -2.2 +/- 2.1 mm, p < 0.0001) and end-systolic (-8.3 +/- 7.0 vs -5.1 +/- 3.7 mm, p = 0.037) dimensions, and a greater decrease in stroke volume (-10 +/- 10 vs -2 +/- 11 ml, p = 0.023) compared with those with a normal response. The groups did not differ significantly with regard to baseline stroke volume, cardiac output, SVR, and LV ejection fraction or LV mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793399 TI - Prognostic implications of mental stress-induced silent left ventricular dysfunction in patients with stable angina pectoris. AB - Thirty patients with stable angina pectoris and ischemia on stress perfusion imaging underwent continuous ambulatory left ventricular (LV) function monitoring. Mental stress was induced by mental arithmetic. Fifteen patients developed transient LV dysfunction during mental arithmetic. Patients were followed for 2 years for adverse cardiac events. Twelve patients had cardiac events over 1 year (myocardial infarction in 4, and unstable angina in 8). Nine of 15 patients (60%) with and only 3 of 15 (20%) without mental stress-induced LV dysfunction developed cardiac events (p = 0.025). A higher proportion of patients with cardiac events were taking beta blockers (p = 0.01) and had lower resting heart rates (p = 0.002) than those without cardiac events. There was no difference in the baseline characteristics between the groups of patients with and without cardiac events. At 2-year follow-up, 10 of 15 patients (67%) with mental stress-induced LV dysfunction had adverse events compared with only 4 of 15 (27%) with no mental stress-induced LV dysfunction (p = 0.025). Thus, in this cohort of patients with stable angina pectoris, mental stress-induced LV dysfunction was associated with higher cardiac events on follow-up. The exact mechanism of this association is not clear. Mental stress may be a trigger for adverse cardiac events in these patients. Transient LV dysfunction in response to mental stress may be a marker of abnormal cardiovascular reactivity to emotional and psychological stimuli in patients with coronary artery disease and may be useful for risk stratification. PMID- 7793400 TI - Importance of baseline functional and socioeconomic factors for participation in cardiac rehabilitation. AB - Enrollment in cardiac rehabilitation has been reported to improve exercise capacity, psychological well-being, and survival. However, participation rates are low and the reasons for nonparticipation have not been adequately defined. The purpose of this study was to evaluate the major correlates of nonparticipation and to examine the level of participation of patients who stand to benefit most on the basis of preenrollment functional status and health behaviors. Three hundred ninety-three patients undergoing coronary artery bypass surgery (1) had baseline functional status and quality-of-life data collected, and (2) were recruited for participation in the Duke Center for Living comprehensive 3-week post-coronary bypass surgery rehabilitation program. Baseline demographic, clinical, catheterization, functional status, psychological status, and health behavior descriptors were analyzed to identify univariate and multivariable correlates of a patient's decision to participate in the program. At baseline, most clinical factors were similar in participants (n = 52) and nonparticipants (n = 341), but the nonparticipants were more often women (26% vs 12%, p = 0.02). Participants were also more likely to be employed (63% vs 45%, p = 0.02) and had a higher education and income distribution than nonparticipants (both p = 0.001). On 2 separate scales, nonparticipants had significantly more baseline functional impairment than participants (both p = 0.001). In multivariable analysis, the independent correlates of higher participation rates were: higher education (college graduates 71% more likely to participate than high school graduates) and better baseline Duke Activity Status Index (patients with mild functional impairment were at least 42% more likely to participate than patients with moderate impairment).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793401 TI - An accurate stepwise electrocardiographic algorithm for localization of accessory pathways in patients with Wolff-Parkinson-White syndrome from a comprehensive analysis of delta waves and R/S ratio during sinus rhythm. AB - Prediction of accessory pathway location before radio-frequency ablation has become increasingly important for patients with Wolff-Parkinson-White syndrome. However, existing electrocardiographic (ECG) criteria for localization of accessory pathways have several limitations, and the polarity of delta waves has not been well defined. In the present study, 369 patients with a single anterogradely conducting accessory pathway who underwent successful radiofrequency ablation were included. The polarity of delta waves was defined and categorized in detail, and various ECG characteristics of the most preexcited QRS complexes were examined and compared with QRS complexes after successful ablation in the initial 182 patients, which included morphology and polarity of delta waves, initial 20, 40, and 60 ms segments of the preexcited QRS complex, R/S ratio in the precordial leads, R/S ratio in the frontal leads, delta wave axis in the frontal plane, polarity of delta waves in the frontal leads, and polarity of delta waves in the precordial leads. The polarity of the initial 40 ms segment of the most preexcited QRS complexes in each of the frontal leads, and the polarity of the initial 60 ms segment of the most preexcited QRS complex in each of the precordial leads proved to be the best representatives of delta wave polarity in the respective leads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793403 TI - Examination of mechano-electrical feedback in the transplanted human heart. AB - Several investigators have demonstrated that changes in atrial or ventricular pressure and size may modulate changes in electrophysiologic properties. The coupling of mechanical and electrical changes in the heart has been termed mechano-electrical feedback and is believed to play a role in arrhythmias observed with mitral valve disease, congestive heart failure, and left ventricular hypertrophy. To avoid confounding influences of the autonomic nervous system on electrophysiologic measurements, we measured right atrial and ventricular pacing thresholds with temporary epicardial pacing wires, right ventricular monophasic action potential duration at 90% repolarization during right ventricular pacing at 600 and 400 ms, donor heart rate, systolic, diastolic, and mean arterial and central venous pressures in 22 patients after orthotopic heart transplantation. Each variable was measured at baseline, in the resting supine state, and during graded lower body negative pressure of -10, -20, and -30 mm Hg. All levels of lower body negative pressure resulted in a significant decrease in mean right atrial pressure up to 5 +/- 6 mm Hg at maximal lower body negative pressure, and a significant decrease in mean arterial pressure occurred only at -20 and -30 mm Hg. Lower body negative pressure did not result in a significant change in any electrophysiologic variable despite significant changes in right atrial pressure. Thus, in the denervated transplanted human heart, unloading of the right heart results in no or small changes in atrial or ventricular pacing thresholds and ventricular monophasic action potential duration. PMID- 7793402 TI - Long-term efficacy of amiodarone for the maintenance of normal sinus rhythm in patients with refractory atrial fibrillation or flutter. AB - The purpose of this study was to examine the efficacy and safety of amiodarone to maintain sinus rhythm in patients with refractory atrial fibrillation or flutter. One hundred ten patients with atrial fibrillation or flutter, refractory to > or = 1 class I antiarrhythmic agents (mean +/- SD 2.5 +/- 1.5, median 2), were given low-dose amiodarone (mean maintenance dose 268 +/- 100 mg/day) to determine its efficacy to maintain normal sinus rhythm after chemical or electrical cardioversion. Fifty-three patients had chronic and 57 patients had paroxysmal atrial fibrillation or flutter. Mean age of the study population was 60 +/- 13 years, and the mean follow-up was 36 +/- 38 months (range 31 days to 137 months). Actuarial rates for maintenance of sinus rhythm were 0.87, 0.70, and 0.55 at 1, 3, and 5 years, respectively. Twenty-one patients (19%) with arrhythmia recurrence had an increase in amiodarone dose, and after a mean additional follow up of 2.5 years, 86% remained in normal sinus rhythm. The only observed predictor of atrial fibrillation or flutter recurrence was paroxysmal arrhythmia (40% recurrence vs 9% in patients with chronic atrial fibrillation or flutter; p < 0.001). Actuarial rates for withdrawal because of adverse effects were 0.08, 0.22, and 0.30 at 1, 3, and 5 years, respectively. The most frequent adverse effects necessitating withdrawal were skin discoloration (4.5%), pulmonary fibrosis (3.6%; none fatal), and thyroid toxicity (2.7%). No deaths occurred during the study period. In conclusion, amiodarone sinus rhythm in patients with atrial fibrillation or flutter, with a relatively low incidence of adverse effects necessitating withdrawal. PMID- 7793404 TI - Impaired low-frequency oscillations of heart rate in patients with prior acute myocardial infarction and life-threatening arrhythmias. AB - Myocardial infarction results in abnormal cardiac autonomic function, which carries an increased risk of cardiac mortality, but it is not well known whether autonomic dysfunction itself predisposes patients to life-threatening arrhythmias or whether it merely reflects the severity of underlying ischemic heart disease. To determine the significance of abnormalities of cardiovascular neural regulation on the risk for ventricular tachycardia (VT), heart rate (HR) variability in the time and frequency domain were compared in a case-control study between 30 patients with a prior myocardial infarction and a history of sustained VT (n = 18) or cardiac arrest (n = 12) (VT group) and 30 patients with a prior myocardial infarction but no arrhythmic events (control group). The patient groups were carefully matched with respect to age, sex, location, ejection fraction, number of prior infarctions, number of diseased coronary arteries, and beta-blocking medication. In all patients in the VT group, inducibility into sustained VT was achieved, but none of the control patients had inducible nonsustained or sustained VT during programmed electrical stimulation. Patients in the VT group had a significantly lower SD of the RR intervals (p < 0.01), and reduced ultra low-, very low-, and low-frequency power spectral components of HR variability (p < 0.001 for all) than controls, but the high frequency component of HR variability did not differ significantly between groups. In multiple regression analysis, reduced very low-frequency power of HR variability was the strongest independent predictor of VT susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793405 TI - Assessment and significance of ST-segment changes detected by ambulatory electrocardiography after acute myocardial infarction. AB - This study assessed the prognostic value of ST-segment changes detected by ambulatory electrocardiographic monitoring during the early in-hospital period after acute myocardial infarction. New methods for defining the ST-segment reference level and for measuring ST-segment elevation were used. ST-segment depression was defined as a change in ST level by > or = 0.1 mV 80 ms after the J point, elapsing > or = 1 minute. ST-segment elevation was defined as a deviation by > or = 0.15 mV, elapsing > or = 1 minute, and measured at the J point. An interval of > or = 2 minutes was required before another discrete episode was counted. Four ST-segment reference levels were automatically calculated: (1) "isoelectric," (2) "nearest to normal," (3) "24-hour median," and (4) "first-hour median." During a mean follow-up period of 3 years (mean 36 +/- 15 months), 47 cardiac events occurred in 38 patients: 18 deaths, 9 nonfatal reinfarctions, and 20 revascularization procedures. More deaths occurred in patients with than without ST elevation-24-hour median (22% vs 5%, p = 0.03), and in patients with than without ST depression-isoelectric (61% vs 32%, p = 0.02), and in patients with than without ST-depression-24-hour median (61% vs 23%, p = 0.003). "All cardiac events" (deaths, infarctions, or revascularization procedures) occurred more often in patients with than without ST depression-isoelectric (55% vs 22%, p = 0.003), and in patients with than without ST-depression-24-hour median (47% vs 17%, p = 0.004). Sensitivity, specificity, and accuracy of ST depression/elevation-24-hour median to assess mortality were 78%, 71%, and 73%, respectively. PMID- 7793407 TI - Deletion within chromosome 22 is common in patients with absent pulmonary valve syndrome. AB - Interstitial deletions in chromosome 22 and features associated with CATCH-22 syndrome have been reported in patients with conotruncal congenital heart anomalies. Absent pulmonary valve syndrome is characterized by absent or rudimentary pulmonary valve cusps, absent ductus arteriosus, conoventricular septal defect, and massive dilation of the pulmonary arteries. Because absence of the ductus arteriosus is a key element in the pathogenesis of this syndrome and aortic arch malformations are frequently seen in patients with CATCH-22 syndrome, we hypothesized that patients with absent pulmonary valve syndrome would have a high incidence of deletions in the critical region of chromosome 22. Eight patients with absent pulmonary valve syndrome were studied. Metaphase preparations were examined with fluorescent in situ hybridization of the N25 (D22S75) probe to the critical region of chromosome 22q11.2. Deletions were detected in 6 of 8 patients. The presence of deletions in chromosome 22 in most of the patients we have examined with a diagnosis of absent pulmonary valve syndrome supports a specific genetic and embryologic mechanism involving the interaction of the neural crest and the primitive aortic arches as one cause of congenital absence of the pulmonary valve. PMID- 7793406 TI - Left ventricular ejection fraction during supine and upright exercise in patients with systemic hypertension and its relation to peak filling rate. AB - In hypertensive patients with hypertrophy, abnormal peak filling rate (PFR) is related to a decline in left ventricular (LV) ejection fraction (EF) during supine exercise. Because an increased LV preload is more common during upright exercise, we determined this relation during upright and supine exercise. In 20 hypertensive patients, rest and exercise radionuclide angiography in the supine and upright positions, as well as echocardiography, were performed and compared with 20 age-matched controls. At rest in the supine and upright positions, blood pressure, LVEF, and PFR were 164 +/- 20/94 +/- 10 and 164 +/- 24/94 +/- 10 mm Hg, 65 +/- 8% and 65 +/- 6%, and 2.77 +/- 0.59 and 2.70 +/- 0.52 end-diastolic volumes/s, respectively. PFR was reduced compared with controls (3.29 +/- 0.3 and 3.27 +/- 0.27 end-diastolic volumes/s, supine and upright). LV mass index was normal (94 +/- 19 g/m2). LVEF increased during upright but not during supine exercise in the hypertensives. Four patients had a decline in each position versus none of the controls. There was no relation between the change in LVEF and rest PFR. In patients with mild to moderate hypertension without extensive hypertrophy, abnormal filling rates were present but did not correlate with the change in LVEF with exercise. PMID- 7793408 TI - Time course of "warm-up" in stable angina. AB - Warm-up exercise can significantly reduce the severity of myocardial ischemia on exercise after a 10-minute rest, but this benefit is significantly less after a 30-minute rest. Further study is needed to clarify the mechanisms responsible for warm-up. The results of this study are consistent with a change in myocardial metabolism similar to ischemic preconditioning or a delayed increase in myocardial perfusion to the ischemic territory, which has returned toward baseline after 30 minutes. PMID- 7793409 TI - Intraaortic balloon pumping as adjunctive therapy to rescue coronary angioplasty after failed thrombolysis in anterior wall acute myocardial infarction. PMID- 7793410 TI - Late angiographic follow-up after Palmaz-Schatz stent implantation. PMID- 7793411 TI - Coronary stenting for acute myocardial infarction. AB - In summary, our experience suggests that coronary stents may play a useful role in carefully selected patients undergoing angioplasty for myocardial infarction. The potential may exist to increase rates of successful infarct artery reperfusion and increase long-term patency. The use of stents in myocardial infarction should probably be reserved for situations in which balloon angioplasty fails. Newer stent designs and anticoagulant regimens may alleviate some of the current concerns with regard to stenting at the time of acute myocardial infarction. PMID- 7793412 TI - Exercise training and blood viscosity in patients with ischemic heart disease. PMID- 7793414 TI - Usefulness of endothelin-1 as a predictor of response to head-up tilt-table testing in children with syncope. PMID- 7793413 TI - Prior restraint: a Bayesian perspective on the optimization of technology utilization for diagnosis of coronary artery disease. AB - In conclusion, at least 1/3 of patients with suspected coronary artery disease are inappropriately referred for scintigraphic diagnostic testing from a Bayesian such as those described in this report, may be a powerful mechanism for encouraging more appropriate technology utilization while simultaneously controlling costs, and are thereby deserving of a formal prospective demonstration trial. However, since only half the patients currently being tested are referred for diagnostic purposes, analogous strategies must be developed with respect to prognostic and therapeutic evaluation. PMID- 7793415 TI - Developmental changes of alpha 1-adrenergic chronotropic action on human sinus node. AB - The important role of alpha 1-adrenoceptors in reperfusion ventricular arrhythmia is mentioned in the introduction. However, the present report is concerned with the sinus node. It is speculated that the decreased positive chronotropic action of alpha 1-adrenergic stimulation due to aging may contribute to the development of sick sinus syndrome. PMID- 7793416 TI - Inadvertent malposition of a transvenous-inserted pacing lead in the left ventricular chamber. AB - In conclusion, we propose the following approach to prevent and manage lead malposition in the left ventricle: A 12-lead electrocardiogram in the paced mode and an anterior and lateral chest view should be thoroughly inspected shortly after pacemaker implantation. A definitive diagnosis of malposition can be established with these tests. Development of any neurologic symptoms should be attributed to the malpositioned lead until proved otherwise. In such patients, serious consideration should be given to transcatheter or surgical lead extraction after a period of anticoagulation. If this is not possible, chronic anticoagulation with warfarin must be initiated, achieving an international normalized ratio of > or = 2.5. Antiplatelet therapy alone may not confer adequate protection against future cerebral events. Furthermore, most patients with neurologic manifestations do not have echocardiographic evidence of thrombus on the lead. Conversely, presence of thrombus is highly associated with neurologic symptoms. Any intraarterial lead must be removed due to inevitable complications. Patients who have remained completely asymptomatic for > or = 3 years may be followed carefully with no therapy. For asymptomatic patients diagnosed before this time period, we recommend empiric therapy with antiplatelet agents or low-dose warfarin (international normalized ratio 1.5-2) with careful observation for symptoms. PMID- 7793417 TI - Relation between saliva cotinine concentration, cigarette consumption, and blood pressure among smokers. AB - In conclusion, we found no evidence of any reduction in blood pressure with greater smoking exposure. For smokers allowed to smoke in a natural manner before blood pressure assessment, greater smoking exposure indexed by saliva cotinine concentration is associated with higher systolic blood pressure levels. PMID- 7793418 TI - A prospective study of the seroprevalence of Borrelia burgdorferi infection in patients with severe heart failure. AB - We conclude that Lyme disease is not a common cause of idiopathic heart failure in the Midwestern United States and that false-positive Lyme disease serologic results are not rare among patients with severe heart failure. Patients with significant cardiac disease who are found to be EIA seropositive should have confirmatory Western blots performed before consideration of treatment. Based on our findings, we cannot recommend either the routine serologic screening of patients with idiopathic cardiomyopathy or aggressive (e.g., parenteral) antibiotic treatment of seropositive patients unless the specific clinical history suggests antecedent Lyme disease. PMID- 7793419 TI - Prevalence and work-relatedness of self-reported carpal tunnel syndrome among U.S. workers: analysis of the Occupational Health Supplement data of 1988 National Health Interview Survey. AB - To estimate the prevalence and work-relatedness of self-reported carpal tunnel syndrome (CTS) among U.S. workers, data from the Occupational Health Supplement of 1988 National Health Interview Survey (NHIS) were analyzed. Among 127 million "recent" workers" who worked during the 12 months prior to the survey, 1.47% (95% CI: 1.30; 1.65), or 1.87 million self-reported CTS, and 0.53% (95% CI: 0.42; 0.65), or 675,000, stated that their prolonged hand discomfort was called CTS by a medical person. Occupations with the highest prevalence of self-reported CTS were mail service, health care, construction, and assembly and fabrication. Industries with the highest prevalence were food products, repair services, transportation, and construction. The risk factor most strongly associated with medically called CTS was exposure to repetitive bending/twisting of the hands/wrists at work (OR = 5.2), followed by race (OR = 4.2; whites higher than nonwhites), gender (OR = 2.2; females higher than males), use of vibrating hand tools (OR = 1.8), and age (OR = 1.03; risk increasing per year). This result is consistent with previous reports in that repeated bending/twisting of the hands and wrists during manual work is etiologically related to occupational carpal tunnel syndrome. PMID- 7793420 TI - Workers' response to risk notification. AB - Since 1988, the National Institute for Occupational Safety and Health (NIOSH) has notified workers who were subjects in occupational epidemiology studies of the study findings ("worker notification"). This paper describes seven notifications and the worker's reactions to them. The chemicals of interest in the studies were: carbon monoxide, o-toluidine, bis-chloromethyl ether, polychlorinated biphenyls, cadmium, acid mist, and dioxin. Materials describing the study results were sent to 15,958 subjects who were notified of their increased risk of arteriosclerotic heart disease, bladder cancer, lung cancer, melanoma, kidney dysfunction, laryngeal cancer, all cancers combined, or soft tissue sarcoma. Workers provided feedback via telephone calls, and for three notifications, by postcards containing workers' comments and ratings of the notification materials. The percentage of telephone calls received from notified workers ranged from 0.3% to 3.8%, and the percentage returning postcards ranged from 8.8% to 17.6%. The two largest categories of callers were those with questions about their disease risk (30%) or who reported on their health status (25%). Most of the comments on postcards (26%) were complimentary or expressed appreciation for receiving the letters; reports of ill health were second (20%). A majority (66%) rated the notification materials well done. Few of the callers (5%) requested information on legal issues. Most (85%) did not find the materials, which ranged in reading level from sixth to ninth grade, too hard to read, although 15% reported difficulty reading them. Although this response system was effective in producing some input from workers, its limitation is that respondents may not be representative of all notified workers. However, such information is useful because there are few data on the effects of notifications on workers. PMID- 7793421 TI - Proportionate mortality among construction laborers. AB - This report presents the results of proportionate mortality ratio (PMR) analyses and proportionate cancer mortality ratio (PCMR) analyses among the 11,685 members of the Laborers' International Union of North America (LIUNA), who died between 1985-1988, using U.S. proportionate mortality rates as the comparison population. Statistically significant elevated mortality risks were observed for all malignant neoplasms (N = 3285, PMR = 1.13, CI = 1.09-1.17), as well as for site specific neoplasms of the lung (N = 1208, PCMR = 1.06, CI = 1.00-1.12), stomach (N = 170, PCMR = 1.44, CI = 1.23-1.68), and thyroid gland (N = 10, PCMR = 2.24, CI = 1.07-4.12). The PCMRs for these malignant neoplasms were elevated among both white and non-white males, regardless of length of union membership, in most 10 year categories of age at death above 40 and for the three largest LIUNA regions examined. The study also observed 20 mesothelioma deaths, which indicated that some LIUNA members had been previously exposed to asbestos. Statistically significant elevated risks were also observed for deaths from transportation injuries (N = 448, PMR = 1.37, CI = 1.25-1.51), falls (N = 85, PMR = 1.34, CI = 1.07-1.66), and other types of injuries (N = 245, PMR = 1.61, CI = 1.42-1.83). The deaths due to injuries were most often observed among those members who had the shortest amount of time within the union, were younger, and first entered the union after 1955. This is the first study that has examined the general mortality experience limited to construction laborers only (Bureau of Census code 869). PMID- 7793422 TI - Perimenstrual symptoms and working conditions among hospital workers in Quebec. AB - Perimenstrual symptoms are among the most common disorders of women. Seven perimenstrual symptoms were related to working conditions among 539 hospital workers in a retrospective cohort questionnaire study, as part of a larger examination of health problems and working conditions of Quebec hospital workers. Only 8% of women had experienced no symptoms of discomfort associated with their last menstrual period. Lower abdominal pain, the most common symptom (58% prevalence), was associated with lifting weights (usually patients) in a logistic regression adjusted for parity and contraceptive use. Back pain, leg pain, swelling, and headache were associated with indicators of time pressure and fast work speed. Back pain during menstruation was experienced by 44% of workers. Studies of the prevalence and etiology of back pain, a common occupational health problem among hospital workers, may be confused if perimenstrual back pain is not taken into account. Similar reservations hold for the results on other perimenstrual symptoms that are also likely to occur outside the perimenstrual period, such as leg pain, irritability, and headache. PMID- 7793423 TI - Tumor markers in serum, polyamines and modified nucleosides in urine, and cytogenetic aberrations in lymphocytes of workers exposed to polycyclic aromatic hydrocarbons. AB - Some polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene and benzo(a)anthracene are well-established genotoxic agents. Long-term exposure to PAHs may lead to proliferative cell disorders in humans, predominantly in the skin, lung, and bladder. The concentration of several tumor markers in serum, of polyamines and modified nucleosides in urine, and of cytogenetic endpoints in peripheral lymphocytes (sister-chromatid exchanges, high frequency cells [HFC], and micronuclei) were measured in 149 male workers exposed to PAHs in two coke oven and one graphite electrode plants, and in 137 controls. We have assessed whether these biomarkers were related to several parameters reflecting exposure to PAHs, i.e., the sum of the airborne concentration of 13 PAHs, 1-hydroxypyrene (1-OHP) concentration in postshift urine, benzo(a)pyrene-diolepoxide adducts to hemoglobin (BPDE-Hb adducts), and duration of exposure, taking also into account several possible confounding factors. HFC was the biomarker most consistently associated with the intensity of current exposure to PAHs. Smoking exerts an independent effect on the same parameter. On the basis of the logistic regression between the prevalence of abnormal HFC values and PAHs in air and 1-OHP in postshift urine found in nonsmokers, it is suggested that the latter should be kept below 6.4 micrograms/m3 and 2.7 micrograms/g creatinine, respectively. No relationship was found between the cytogenetic effects and BPDE-Hb adducts although both parameters are statistically correlated with the airborne PAH level. Some tumor markers in serum (carcinoembryonic antigen, tissue polypeptide antigen, sialic acid) and the urinary concentration of some polyamines were correlated with either PAHs in air or 1-OHP in urine. The associations, however, were very weak which suggests that these biomarkers have limited practical value for the health surveillance of groups of workers exposed to genotoxic PAHs. PMID- 7793425 TI - Occupational exposure of deck crews to carcinogenic agents on crude oil tankers. AB - Occupational exposure to carcinogenic agents on the decks on six Norwegian crude oil tankers was examined in five harbors. The purpose of the study was to evaluate the need for improving the working environment on deck on these tankers. Technical arrangements and the work itself on the deck were observed during loading or unloading. Occupational monitoring was performed by active sampling of benzene, polyaromatic hydrocarbons, and some aldehydes. The crew answered a questionnaire concerning their work, use of protective equipment, and occurrence of acute symptoms. The levels of air-borne carcinogenic agents were low, probably due to closed loading systems on all tankers. However, the seamen reported discomfort during the work that may be related to other chemical agents in the cargo. The seamen were frequently painting with lead chromate paint without using personal protective equipment. This type of chemical exposure should be evaluated. PMID- 7793424 TI - Irritant dermatitis among workers cleaning up a pesticide spill: California 1991. AB - An outbreak of dermatitis occurred among county jail inmates who removed dead fish from the Sacramento River in California after a spill of metam sodium. The spilled chemical decomposes to methylisothiocyanate (MITC), a known skin irritant. A retrospective cohort study was conducted among the inmates and their crew leaders. Among 42 jail group members, 27 had dermatitis involving the feet and ankles; dermatitis was associated with lower extremity water contact (RR = 3.4, 95% CI 1.0-11.8); the attack rate increased with length of time spent in the water. For comparison, other state and federal employees who worked in the river at the same time were also interviewed. None reported dermatitis. Over three quarters (24/31) of these other clean-up workers whose feet became wet changed to dry clothing immediately; none of the jail group changed immediately. The river concentration of MITC measured 20-40 ppb at the time of exposure. We speculate that prolonged wetness, occlusive boots, friction, and heat contributed to chemical irritation at this low concentration; the experience of the other clean up workers suggests that this outbreak could have been prevented. PMID- 7793426 TI - Relationship between locations of chromosome breaks induced by vinyl chloride monomer and lymphocytosis. AB - The distribution of vinyl chloride monomer (VCM)-induced chromosome breaks was studied in cultured lymphocytes of subjects occupationally exposed to this gas. In the examined subjects, the mean group value of chromosome aberrations is 6.5% and for sister chromatid exchange (SCE) frequencies, the mean value per cell is 7.9. These values are significantly higher than in the control population. Occupational exposure to VCM caused lymphocytosis together with disturbances of mitogenic activity in lymphocytes stimulated by phytohaemagglutinin. The results of G-banding showed that sites of chromosome breakpoints caused by VCM can be related to the lymphatic tissue disorders. PMID- 7793427 TI - Malignant mesothelioma in thermoelectric power plant workers in Italy. AB - Asbestos has been widely used in Italian thermoelectric power plants and instances of exposure to workers have been documented in a variety of jobs. Preventive measures were put into effect only in the late 1970s. We report here on four mesothelioma cases among workers of three Italian power plants where cohort studies were carried out, and on three additional cases recorded by a systematic survey carried out on this neoplasm in Tuscany. When the data of the cohorts sources are merged, a significant excess of lung cancer is also evident. Even without a quantitative assessment of exposure, this report shows the importance of asbestos risk in thermal power plants. The risk appears not to be restricted to any particular category of workers. PMID- 7793429 TI - Fibers in lung tissues of mesothelioma cases among miners and millers of the township of Asbestos, Quebec. AB - Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 microns, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers > or = 5 microns were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 microns, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 microns were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases. PMID- 7793430 TI - Chronology of asbestos cancer discoveries: experimental studies of the Saranac Laboratory. AB - This commentary challenges a recently published perception that Dr. Le Roy Upson Gardner had not actually discovered in 1942 that inhaled chrysotile fibers could induce malignant neoplasia in mice. The handwritten laboratory notes and some of Dr. Gardner's slides have recently been found. They verify that the tumors he saw in the mice included truly malignant neoplasms. Gardner had by then also accumulated 11 cases of human lung cancer (two mesotheliomas) derived from Quebec asbestos miners and millers. An inhalation study designed by Dr. Gardner and conducted between 1951 and 1954, using cancer-insusceptible mice, yielded neoplasia risk ratio of 5.7 compared with control animals. The studies also showed that the primary effect of chrysotile is to cause epithelial proliferation in alveoli adjacent to bronchioles. Chrysotile type asbestos bodies were shown to remain only transiently ferruginous, but even though invisible in direct light they can be visualized at high magnification through use of phase contrast and polarized light micrography. PMID- 7793431 TI - Re: Epidemiological studies of paternal exposure and spontaneous abortion. PMID- 7793428 TI - Pleural mesotheliomas are underreported as occupational cancer in Sweden. AB - The aim of this study was to estimate to what degree malignant pleural mesotheliomas were reported as occupational cancers. The study included all malignant pleural mesotheliomas (n = 210) found in the Cancer Registry 1980-1989 from four Swedish counties. Whether or not a case was reported as occupational cancer was found in the Swedish Register of Reported Occupational Diseases. To evaluate the presence of exposure histories, the chest department files for 58 mesotheliomas from one county were reviewed. The reporting was low, with only 75 mesotheliomas (36%) reported. All the cases were men, and for the men, the reporting frequency was 42%. The reporting was significantly lower for the last part of the decade than for the first part. The reporting frequency decreased with age. In the review of the chest department files, an exposure history was found in 93% of the reported cases and in 47% of the unreported cases. It is concluded that physicians must give more priority to exposure histories in patients with pleural mesotheliomas. PMID- 7793432 TI - Paternal occupational exposure and spontaneous abortions: a closer look at paternal recall and vinyl chloride. PMID- 7793433 TI - Silicosis risk: Canadian and South African miners. PMID- 7793434 TI - Role of the family in recovery and major depression. AB - OBJECTIVE: Major depression is significantly influenced by the family environment of the depressed patient. In order to explore how family functioning relates to this illness, the authors examined changes in family functioning over a 1-year course of major depression. METHOD: Subjective (Family Assessment Device) and objective (McMaster Clinical Rating Scale) assessments of family functioning were collected at hospitalization and 6 and 12 months after discharge for 45 inpatients diagnosed with major depression and their family members. Patterns of family functioning were examined by subjective and objective perspectives, initial levels of functioning, and reports of patients and other family members. RESULTS: Approximately 50% of families with a depressed member perceived their own family functioning as unhealthy; clinicians rated 70% of the families as unhealthy. While family functioning improved significantly from hospitalization through 12 months after discharge, the improvement was not uniform across all areas of functioning. Further, patients with good family functioning at hospitalization generally maintained their healthy functioning and were more likely to recover by 12 months than patients with poor family functioning. Although steady improvement in family functioning characterized the subjective ratings, objective assessments of family functioning suggested initial improvement followed by a decline from month 6 to month 12. CONCLUSIONS: Results show a clear association between family functioning and recovery from major depression. Different aspects of family life respond differently to the depressive illness; no one family dimension was uniquely related to outcome. PMID- 7793435 TI - Vulnerability to psychosis in unipolar major depression: is premorbid functioning involved? AB - OBJECTIVE: This research examined whether deficits in premorbid functioning are associated with a vulnerability to psychosis in unipolar major depressive disorder. METHOD: A group of 92 inpatients with unipolar major depression were assessed for premorbid functioning and psychotic symptoms during an index hospitalization. They were prospectively assessed for psychotic symptoms 2.0 and 4.5 years after hospital discharge. RESULTS: The psychotic depressed patients had significantly poorer premorbid functioning--particularly, adolescent social functioning--than the nonpsychotic depressed patients. Longitudinal analyses indicated that poor premorbid social adaptation was significantly associated with the emergence of psychosis during the follow-up period in depressed patients who had not been psychotic as inpatients. CONCLUSIONS: Factors related to a vulnerability to psychosis among patients with major depression are present even years before the onset of overt psychotic symptoms. The data could support the view that impaired premorbid functioning is one manifestation of prepsychotic processes that constitute an underlying diathesis for psychotic episodes during the longitudinal course of unipolar major depression. These findings are consistent with other emerging findings pointing to early developmental deficits in patients who subsequently develop psychotic disorders. PMID- 7793436 TI - Rates of seasonal affective disorder in children and adolescents. AB - OBJECTIVE: The authors estimated the frequency of seasonal affective disorder in children and adolescents and examined the relationship of this rate to age and pubertal status. METHOD: A modified version of the Seasonal Pattern Assessment Questionnaire was distributed to 2,267 students at a middle school and a high school in a suburb of Washington, D.C. A case diagnosis was made if the respondent scored over 18 and also indicated that the change of seasons was at least a "pretty bad" problem. RESULTS: A total of 1,871 questionnaires (82.5%) were returned. Sixty probable cases of seasonal affective disorder (3.3%) were identified among the 1,835 surveys analyzed. Age was directly correlated with the frequency of seasonal affective disorder, and the rate was higher in postpubertal girls. Differences between the subjects with and without identified cases of seasonal affective disorder were seen in the symptom endorsement patterns, particularly for "feel worst," "least energy," "most irritable," and "socialize least." CONCLUSIONS: These pilot data suggest that between 1.7% and 5.5% of 9-19 year-old children may have seasonal affective disorder. Further research is warranted, particularly that which examines the relationship between seasonal affective disorder and puberty. PMID- 7793437 TI - Mental health and choice between managed care and indemnity health insurance. AB - OBJECTIVE: Populations enrolled in various health insurance plans may differ in their health care needs. Whether mental health affects choice among competing health plans is not clear. This study examined self-selection by participants in a Swiss indemnity insurance plan that was transformed into a managed care organization that controlled access to specialists through gatekeeping and restricted coverage for psychiatric treatments. METHOD: Information regarding past use of health services and health status was provided by 421 persons who joined the new managed care organization and 222 nonjoiners. The mental health and somatic health characteristics of these two groups were compared. RESULTS: In the year preceding the creation of the managed care organization, the nonjoiners had made on average 2.3 more visits to psychiatrists than the joiners but 0.0 to 0.6 more visits to other physicians. The nonjoiners were more likely to have used psychoactive medications but not other medications. The rates of treatment for depression were similar in the two groups. The joiners reported significantly lower mental health status, but not somatic health status, than the nonjoiners. CONCLUSIONS: Both mental health status and past use of mental health services strongly affected choice of health insurance plan. The effects of somatic health and use of somatic health services on selection were consistently weaker. People who join managed care organizations may have substantial uncovered needs for psychiatric care. Minimum mandatory benefits for mental health care may be an effective countermeasure to unequitable self-selection. PMID- 7793438 TI - Social consequences of psychiatric disorders, I: Educational attainment. AB - OBJECTIVE: This is the first in a series of investigations of the social consequences of psychiatric disorders based on the National Comorbidity Survey. Data on the relationship between preexisting psychiatric disorders and subsequent educational attainment are presented. METHOD: The National Comorbidity Survey is a nationally representative survey of 8,098 respondents in the age range 15-54 years. A subsample of 5,877 respondents completed a structured psychiatric interview and a detailed risk factor battery. Diagnoses of DSM-III-R anxiety disorders, mood disorders, substance use disorders, and conduct disorder were generated, and survival analyses were used to project data on school terminations to the total U.S. population. RESULTS: Early-onset psychiatric disorders are present in more than 3.5 million people in the age range of the National Comorbidity Survey who did not complete high school and close to 4.3 million who did not complete college. The most important disorders are conduct disorder among men and anxiety disorders among women. The proportion of school dropouts with psychiatric disorders has increased dramatically in recent cohorts, and persons with psychiatric disorders currently account for 14.2% of high school dropouts and 4.7% of college dropouts. CONCLUSIONS: Early-onset psychiatric disorders probably have a variety of adverse consequences. The results presented here show that truncated educational attainment is one of them. Debate concerning whether society can afford universal insurance coverage for the treatment of mental disorders needs to take these consequences into consideration. PMID- 7793439 TI - Comparison of standards for assessing patients' capacities to make treatment decisions. AB - OBJECTIVE: This study investigated the proportion of psychiatric and medical patients who are impaired in their decision-making abilities in relation to each of several major legal standards for determining competence to consent to treatment. METHOD: The subjects were hospitalized patients with diagnoses of schizophrenia (N = 75), major depression (N = 92), and ischemic heart disease (N = 82) and equal numbers of community comparison subjects matched on age, race, gender, education, and occupation. Three instruments measuring abilities related to the legal standards for competence were administered to each group. Impaired functioning was defined as scores two standard deviations below the means for all subjects combined or lower. RESULTS: Although similar percentages of subjects with impaired performance were found for each of the measures, different groups of patients were identified as impaired depending on the measure used. The proportion of patients identified as impaired increased when compound standards were used, i.e., when impairment was defined as poor performance on any of two or three measures. Despite previous suggestions that the legal standards might form a hierarchy of rigorousness, the data did not support this hypothesis. CONCLUSIONS: Choice of standards for determining competence, including compound standards, will affect the identity and proportion of patients classified as impaired. Clinicians should be aware of applicable standards in their jurisdictions. Use of compound standards requires independent evaluation of performance on abilities related to each relevant standard, because standards do not appear to be hierarchical. Policies relating to the characterization of persons as incompetent must be fashioned with caution. PMID- 7793440 TI - Hospital use of antipsychotic agents in 1989 and 1993: stable dosing with decreased length of stay. AB - OBJECTIVE: This study evaluated recent and current use of antipsychotics by psychiatric inpatients. METHOD: Computer-based hospital pharmacy records identified prescriptions for antipsychotics in 1993. Medical records were reviewed to verify prescription and clinical data, and these were compared with similar data from 1989. RESULTS: In 1993, antipsychotics were prescribed for 299 (42%) of 709 hospitalized patients. Treatment usually started within 24 hours of admissions averaging 18 days. High-potency agents were used 2.4 times more frequently than low-potency drugs; 13% received clozapine. The mean chlorpromazine-equivalent daily dose, corrected for as-needed supplements, was 305 mg; peak doses were 32% higher. Doses of the most potent agents (fluphenazine and haloperidol) were only 22%-33% above the overall mean. Rarely were two neuroleptics given simultaneously, but cotreatment with an anticonvulsant (84% of patients, 92% of whom received valproate), a potent benzodiazepine (81%), lithium (70%), one CNS depressant (84%), or more (45%) was common. Doses averaged 20% higher for men, 42% lower at age > 50 years versus 20-30 years, and 53% greater for schizophrenia or schizoaffective disorder versus other conditions. Comparison with 1989 admissions (N = 50) averaging 73 days indicated few differences in use of neuroleptics or benzodiazepines but less frequent use of anticonvulsants and lithium. CONCLUSIONS: High-potency antipsychotic agents and clozapine were used most often in 1993; doses of high-potency agents were only slightly higher than doses of low-potency agents, but combinations with mood stabilizers were more common in 1993, when length of stay was one-fourth that in 1989. PMID- 7793441 TI - Chronic alcoholism and male sexual function. AB - OBJECTIVE: The relation between chronic alcohol abuse and male sexuality remains uncertain. This study assessed the effect of chronic alcoholism on sexual function, marital adjustment, sleep-related erections, sleep disorders, and hormone levels during abstinence from alcohol. METHOD: Twenty chronically alcoholic men, aged 28-59 years, without evidence of severe hepatic disease and free from unrelated medical illnesses, were assessed 2-36 months after achieving sobriety and compared to a group of 20 nonalcoholic volunteers. Each subject and his sexual partner underwent semistructured interviews and completed several questionnaires; the men had medical and psychiatric evaluations and polygraphic assessment of sleep parameters and nocturnal penile tumescence during 4 nights, with the last night devoted to sequential blood sampling for evaluation of hormone levels. RESULTS: The alcoholic men did not differ from the comparison group in any sexual dimension or in the prevalence of sexual problems despite the significant marital dissatisfaction reported by their sexual partners. In addition, there were no differences between groups in sleep and nocturnal penile tumescence measures. The alcoholic group had a greater prevalence of periodic leg movement disorders but no respiratory abnormalities during sleep. Except for a significant overnight increase in plasma luteinizing hormone in the alcoholic men, there were no differences between groups in total and bioavailable testosterone, dihydrotestosterone, and prolactin or in the nocturnal circadian changes in testosterone and prolactin levels. CONCLUSIONS: These findings suggest that prolonged and severe alcohol abuse in men is compatible with normal sexual function during sobriety in the absence of substantial hepatic or gonadal failure. PMID- 7793442 TI - Bulimia nervosa in a Canadian community sample: prevalence and comparison of subgroups. AB - OBJECTIVE: Previous epidemiological studies of bulimia nervosa have generated differing estimates of the incidence and prevalence of the disorder. These differences are attributable, in part, to varying definitions of the illness and a range of methodologies. The authors sought to define the prevalence of bulimia nervosa in a nonclinical community sample, examine the clinical significance of DSM-III-R threshold criteria, and examine comorbidity. METHOD: Subjects across Ontario (N = 8,116) were assessed with a structured interview, the World Health Organization Composite International Diagnostic Interview, with specific questions added for bulimia nervosa. Subjects who met DSM-III-R criteria for bulimia nervosa were compared with those who were missing only the frequency criterion (two or more binge-eating episodes per week for 3 months). RESULTS: In this sample, the lifetime prevalence of bulimia nervosa was 1.1% for female subjects and 0.1% for male subjects. The subjects with full- and partial-syndrome bulimia nervosa showed significant vulnerability for mood and anxiety disorders. Lifetime rates of alcohol dependence were high in the full-syndrome group. Rates of parental psychopathologies were high in both bulimic groups but tended to be higher in the subjects with full-syndrome bulimia nervosa. Both bulimic groups were significantly more likely to experience childhood sexual abuse than a normal female comparison group. CONCLUSIONS: This study confirms other prevalence estimates of bulimia nervosa and its comorbid diagnoses from studies that were based on sound methodologies. It also points to the arbitrary aspects of the frequency of binge eating as a diagnostic threshold criterion for the disorder. PMID- 7793444 TI - Pilot study of current factors influencing the choice of psychiatry as a specialty. AB - OBJECTIVE: This is a time of major shifts in the perception of medical specialties. The authors have attempted to assess current attitudes of potential applicants for a residency in psychiatry. METHOD: Pilot interviews with fourth year medical students at the University of California, San Francisco, led to the development of a questionnaire on factors influencing the choice of psychiatry as a specialty. The questionnaire was then sent to 113 fourth-year students with an identified psychiatric interest at nine schools. RESULTS: There was a response rate of 50.4%. The 54 students with a clear career decision had 22 of 38 item responses that significantly distinguished between those who matched in psychiatry and those who chose other specialties. CONCLUSIONS: Focused recruitment strategies are suggested based on answers to the questionnaire items. PMID- 7793443 TI - Borderline personality disorder symptoms and severity of sexual abuse. AB - OBJECTIVE: This study explored the relationship of specific symptoms of borderline personality disorder to dimensions of severity of sexual abuse experiences in childhood. METHOD: A group of 41 patients with borderline personality disorder who retrospectively reported a childhood history of sexual abuse on the Familial Experiences Interview were studied. Six items from the Diagnostic Interview for Borderline Patients (DIB) were chosen on the basis of their univariate (chi-square) association with a sexual abuse severity scale that was developed by the authors and their research team. These six DIB items were each modeled in a logistic regression. Predictor variables were the most severe experience within each of three dimensions of sexual abuse: 1) perpetrator (sexual abuse by a parent), 2) duration (sexual abuse that was ongoing), and 3) type (sexual abuse that involved penetration). RESULTS: The severity dimension that was most frequently found to be a significant predictor of the sum of the six DIB items as well as the total scaled DIB score was the duration dimension. Ongoing sexual abuse predicted parasuicidal behavior as well. CONCLUSIONS: Ongoing sexual abuse may be a strong determinant of specific aspects of the disordered interpersonal behavior and functioning found in patients with borderline personality disorder. The expectation that the world is an empty, malevolent place may have some of its roots in the repetition of sexual abuse experiences in childhood. This expectation of malevolence among patients with borderline personality disorder may manifest itself in psychotherapy through regressive and distancing behavior. PMID- 7793445 TI - Low discharge weight and outcome in anorexia nervosa. AB - OBJECTIVE: Because recent limitations in health care coverage have resulted in shorter lengths of inpatient stay, many patients with anorexia nervosa are discharged while still underweight. The authors' goal was to determine whether anorectic patients who were underweight when they were discharged had a worse outcome and a higher rate of rehospitalization than those who had achieved normal weight at discharge. METHOD: They assessed weight and height, eating disorder symptoms, and severity of depressive and anxiety symptoms in 22 women with anorexia nervosa at hospital admission and at follow-up a mean of 29 months after discharge. RESULTS: Anorectic patients who were discharged while severely underweight reported significantly higher rates of rehospitalization and endorsed more symptoms than those who had achieved normal weight before discharge. CONCLUSIONS: These data suggest that brief hospitalization for severely underweight women with anorexia may not be cost effective because the majority are rehospitalized. PMID- 7793446 TI - Mortality in anorexia nervosa. AB - OBJECTIVE: The author's goal was to shed light on the debate regarding the mortality rate over time associated with anorexia nervosa. METHOD: He conducted a meta-analytic study using weighted linear regression to combine crude mortality proportions from 42 published studies to estimate the mortality associated with anorexia nervosa over time. RESULTS: The crude rate of mortality due to all causes of death for subjects with anorexia nervosa in these studies was 5.9% (178 deaths in 3,006 subjects). The aggregate mortality rate was estimated to be 0.56% per year, or approximately 5.6% per decade. CONCLUSIONS: The aggregate estimated mortality rate for subjects with anorexia nervosa is substantially greater than that reported for female psychiatric inpatients and for the general population. PMID- 7793447 TI - Attempted suicide among living co-twins of twin suicide victims. AB - OBJECTIVE: The authors hypothesized that significantly more living monozygotic than dizygotic co-twins of twin suicide victims would themselves have attempted suicide. METHOD: They determined the absence or presence of an attempt at suicide at any time among 26 living monozygotic co-twins and nine living dizygotic co twins of twins who had committed suicide. RESULTS: They found that 10 of the 26 surviving monozygotic co-twins but none of the nine surviving dizygotic co-twins had themselves attempted suicide. CONCLUSIONS: Although monozygotic and dizygotic twins may have some differing developmental experiences, these results contribute to findings of previous studies of suicide in twins in suggesting that genetic factors may play a role in suicidal behavior. PMID- 7793448 TI - A quarter century of suicide in a major urban jail: implications for community psychiatry. AB - OBJECTIVE: The authors' goal was to identify factors that increase the risk of suicide in urban jails. METHOD: They examined and verified all suicides as of 1992 in a representative large jail in Detroit since the beginning of record keeping in 1967 to 1992. RESULTS: There were 37 suicides over this time period. Inmates charged with murder or manslaughter were 19 times more likely to commit suicide than were inmates with other charges. Thirty-nine percent of the suicides were committed by individuals charged with murder. All 37 suicides were by hanging, and most occurred at night within 31 days of admission. Many of the inmates who committed suicide had made previous attempts while incarcerated. Thirty-nine percent of the suicides were committed by individuals charged with murder, constituting 2% of the admissions (two per day). CONCLUSIONS: An important risk factor in jail suicide not previously identified is the charge of murder or manslaughter. Treatment and prevention programs should recognize these inmates as belonging in a very high-risk category. PMID- 7793450 TI - Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. AB - OBJECTIVE: Because they found in an earlier study that inositol, an important intracellular second-messenger precursor, was effective against depression in open and double-blind trials, the authors studied its effectiveness against panic disorder. METHOD: Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, 4-week, random assignment crossover treatment trial of 12 g/day of inositol. RESULTS: The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration. Side effects were minimal. CONCLUSIONS: The authors conclude that inositol's efficacy, the absence of significant side effects, and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder. PMID- 7793449 TI - Discrimination between panic disorder and generalized anxiety disorder by 35% carbon dioxide challenge. AB - OBJECTIVE: The authors' goal was to determine whether 35% carbon dioxide (CO2) challenge would discriminate between patients with panic disorder and patients with other anxiety disorders. METHOD: Nine patients with panic disorder and nine with generalized anxiety disorder underwent the 35% CO2 challenge. RESULTS: Patients with panic disorder experienced a significantly stronger increase in subjective anxiety than patients with generalized anxiety disorder. However, increases in panic symptom scores were high in both groups. CONCLUSIONS: These results suggest that a large increase in subjective anxiety due to the CO2 challenge is specific for patients with panic disorder but that an increase in panic symptoms is not. PMID- 7793451 TI - Lack of effect of clonidine on stuttering in children. AB - OBJECTIVE: The authors studied the effects of the alpha 2-receptor agonist clonidine on stuttering in children. METHOD: Using a double-blind crossover study, they gave placebo or 4 micrograms/kg body weight per day to 25 stuttering children who were 6-13 years old. Stuttering was measured by counting the occurrences of four elementary speech difficulties and by asking parents and teachers to give an overall impression of the amount of stuttering, as well as their impression of how troublesome the stuttering was to the children. RESULTS: Clonidine did not improve stuttering. CONCLUSIONS: Clonidine cannot be recommended as a useful drug for treating children who stutter. PMID- 7793452 TI - Fluvoxamine augmentation for clozapine-resistant schizophrenia. PMID- 7793454 TI - Venlafaxine for adult ADHD. PMID- 7793455 TI - Adult ADHD and AIDS. PMID- 7793453 TI - Effects of venlafaxine treatment for ADHD in a child. PMID- 7793456 TI - Dysphoria after treatment with ondansetron. PMID- 7793457 TI - Sinus arrest in a catatonic patient. PMID- 7793458 TI - Fever associated with clozapine administration. PMID- 7793459 TI - Complete anticoagulation for treatment of neuroleptic malignant syndrome? PMID- 7793460 TI - Renaming multiple personality disorder. PMID- 7793461 TI - Treatment of dysthymia with antidepressants. PMID- 7793462 TI - Effect of gun control legislation on suicide. PMID- 7793463 TI - Corpus callosum morphology in ADHD. PMID- 7793464 TI - Posttraumatic stress disorder: psychology, biology, and the manichaean warfare between false dichotomies. PMID- 7793465 TI - Cortex, IX. Heschl's gyrus and the planum temporale. PMID- 7793466 TI - Prodromes and precursors: epidemiologic data for primary prevention of disorders with slow onset. AB - OBJECTIVE: The concepts of prodrome and precursor are used to show how epidemiologic data on age at onset can be used in timing preventive interventions and selecting target populations. METHODS: Data concerning onset of DSM-III major depression and panic disorder were taken from the Epidemiologic Catchment Area Program. Cumulative distributions of ages at onset of diagnosis and onset of precursors are presented, and the concept of attributable risk is introduced. Attributable risk is the maximum proportion of cases that would be prevented if an intervention were 100% effective in eliminating a specific precursor. RESULTS: Illustrative results for depression and panic are presented. Precursors vary in the degree to which they predict onset of the full disorder; 2 or more weeks of sad mood in the year before full-blown depression is a better predictor (relative odds, 7.0) than weight loss or gain (relative odds, 3.0). The formula for population attributable risk was applied to the precursor relative risks and prevalences to estimate the potential success of interventions for specific precursors in preventing the disorder. The precursor attributable risks indicate that sleep problems would identify 47% of the new cases of major depression occurring in the following year, and the question "Are you a nervous person?" would identify 60% of persons with onset of panic disorder in the following year. CONCLUSIONS: This conceptual framework links the early natural history of disorders with the search for syndromes. Knowledge of precursor prevalence and attributable risk, combined with other host characteristics and environmental risk factors, can be used in screening and prevention. PMID- 7793467 TI - MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. AB - OBJECTIVE: Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. METHOD: Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. RESULTS: The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. CONCLUSIONS: These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory. PMID- 7793468 TI - Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. AB - OBJECTIVE: The authors' objective was to compare the urinary cortisol excretion of Holocaust survivors with posttraumatic stress disorder (PTSD) (N = 22) to that of Holocaust survivors without PTSD (N = 25) and comparison subjects not exposed to the Holocaust (N = 15). METHOD: Twenty-four-hour urine samples were collected, and the following day, subjects were evaluated for the presence and severity of past and current PTSD and other psychiatric conditions. RESULTS: Holocaust survivors with PTSD showed significantly lower mean 24-hour urinary cortisol excretion than the two groups of subjects without PTSD. Multiple correlation analysis revealed a significant relationship between cortisol levels and severity of PTSD that was due to a substantial association with scores on the avoidance subscale. CONCLUSIONS: The present findings replicate the authors' previous observation of low urinary cortisol excretion in combat veterans with PTSD and extend these findings to a non-treatment-seeking civilian group. The results also demonstrate that low cortisol levels are associated with PTSD symptoms of a clinically significant nature, rather than occurring as a result of exposure to trauma per se, and that low cortisol levels may persist for decades following exposure to trauma among individuals with chronic PTSD. PMID- 7793469 TI - Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. AB - OBJECTIVE: The authors recently reported smaller basal ganglia volumes for patients with HIV-associated dementia than for HIV-infected patients without dementia and a seronegative comparison group. The purpose of the current study was to determine whether HIV dementia is associated with volume reductions in other brain regions. METHOD: The authors measured volumes of CSF and gray and white tissue on cranial magnetic resonance images from homosexual men who were 1) infected with HIV with HIV-associated dementia complex, 2) infected with HIV without dementia, and 3) HIV seronegative. RESULTS: Results suggest that loss of white matter occurs with HIV infection and is more severe in HIV-positive patients with dementia than in those without dementia. There was some generalized volume reduction in gray matter in HIV-positive demented patients, although group differences did not reach significance when adjusted for age. Volume of posterior cortex, however, was significantly smaller among HIV-positive patients with dementia than in either remaining group. There were no significant differences between HIV-positive nondemented patients and HIV-negative subjects in these regions. CONCLUSIONS: In conjunction with findings from previous research, the authors conclude that HIV dementia is associated with specific gray matter volume reduction in basal ganglia and posterior cortex, as well as with generalized volume reduction of white matter. PMID- 7793470 TI - Predictors of retrograde amnesia following ECT. AB - OBJECTIVE: Substantial progress has been made in identifying how the treatment parameters used in ECT impact on cognitive side effects. However, there is limited information regarding individual differences in vulnerability to these side effects. The authors examined patients' pretreatment global cognitive status and postictal orientation recovery time as potential predictors of the magnitude of retrograde amnesia for autobiographical memories after ECT. METHOD: Seventy one inpatients with major depressive disorder were randomly assigned to four ECT conditions that varied in electrode placement (right unilateral versus bilateral) and stimulus dosage (low versus high intensity). Orientation recovery time was assessed at virtually every session during the course of ECT. Global cognitive status was assessed with the modified Mini-Mental State examination before treatment, during the week after termination of treatment, and 2 months after treatment ended. Retrograde amnesia was assessed at these same time points with the Autobiographical Memory Interview. RESULTS: Pre-ECT global cognitive status and the duration of postictal disorientation were strong predictors of the magnitude of retrograde amnesia in the week after the course of ECT and at 2 month follow-up. In general, these relationships were maintained regardless of technical parameters in the administration of the ECT. CONCLUSIONS: Patients who manifest global cognitive impairment before treatment and patients who experience prolonged disorientation in the acute postictal period may be the most vulnerable to persistent retrograde amnesia for autobiographical information. PMID- 7793473 TI - Cellular benign mesenchymal tumors of the uterus. A comparative morphologic and immunohistochemical analysis of 33 highly cellular leiomyomas and six endometrial stromal nodules, two frequently confused tumors. AB - Thirty-three highly cellular leiomyomas of the uterus from patients 29 to 65 (mean, 46) years of age and six endometrial stromal nodules from patients 41 to 53 (mean, 46) years of age are described. The patients usually presented with irregular uterine bleeding. Twenty-eight of the leiomyomas were intramural and five, submucosal. Eleven of 18 whose consistency is known were soft, fish-flesh, or rubbery, 10 were yellow or yellow-tan; one had a prominent cystic component. The tumors ranged from 0.5 to 15 cm (mean, 4.6 cm) in maximum dimension. On microscopic examination, they were densely cellular and composed of cells that ranged from round to spindle-shaped and had scanty cytoplasm. A focal fascicular pattern was present in all of the cases. Blood vessels were typically large; thick muscular walls and focally dilated lumens were a conspicuous feature of the majority of the neoplasms. Arterioles were evident focally in most of the tumors but were prominent in only one of them. Cleft-like spaces, some representing compressed vessels, others due to internodular edema, were present in 24 of the tumors and were conspicuous in 15 of them. The neoplasms typically exhibited focal irregular extension into the adjacent myometrium, and this feature was conspicuous in 18 of them. They often merged almost imperceptibly with the adjacent myometrium. All tumors were immunoreactive for desmin and 32 of 32 for alpha-smooth muscle actin. Two of the stromal nodules were polypoid intracavitary masses, three were submucosal, and one intramural. Five were completely or predominantly solid with cysts present focally in three of them; one tumor was predominantly cystic. The solid tissue was frequently yellow. Microscopic examination disclosed a diffuse growth of closely packed small cells with scanty cytoplasm and nuclei that lacked atypia. Three neoplasms contained cells with abundant foamy cytoplasm that were immunoreactive for CD68, indicating that they were histiocytes and not neoplastic cells. All the neoplasms had a prominent component of arterioles, which in one tumor had hyalinized walls. Five tumors were entirely well circumscribed and one predominantly well circumscribed with limited extension into the adjacent myometrium. The tumors were immunohistochemically negative for desmin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7793472 TI - Lipomatous hemangiopericytoma. A histologic, ultrastructural and immunohistochemical study of a unique variant of hemangiopericytoma. AB - We report three cases of a unique, previously undescribed soft tissue tumor composed of mature adipocytes and hemangiopericytomatous areas, for which we propose the term lipomatous hemangiopericytoma. The tumors occurred in adults and were located in the sinonasal area, the soft tissue of the shoulder, and the retroperitoneum. The tumors ranged in size from 4 to 10 cm in greatest diameter and grossly were solid and ranged from tan to yellow. Histologically, they were composed of a variable admixture of benign lipomatous and hemangiopericytomatous components. Immunohistochemically, they stained with antibodies to vimentin and not to alpha-smooth-muscle actin, muscle-specific actin, desmin, S-100 protein, glial fibrillary acidic protein, epithelial membrane antigen, or keratin. Ultrastructurally, the cells constituting the hemangiopericytomatous areas had the features of pericytes, and no lipoblasts or transitional forms between lipocytes and pericytes were found. The histologic differential diagnosis of this neoplasm includes spindle-cell lipoma, angiolipoma, liposarcomas, tumors showing smooth muscle and adipocytic differentiation, and hemangiopericytoma infiltrating fat. Because of the small number of cases and the limited follow-up, we cannot be certain of their biologic behavior, although we expect that they are benign. Lipomatous hemangiopericytoma represents a distinctive pathologic entity that should be recognized and studied further. PMID- 7793471 TI - Adenosis of the prostate. Histologic features in needle biopsy specimens. AB - Classically, adenosis has been described as occurring in the transition zone of the prostate, a region not routinely sampled with needle biopsies. However, with urologists performing more needle biopsies, we have seen an increasing number of cases of adenosis in needle biopsies of the prostate. To better characterize the histologic features of adenosis present in needle biopsy specimens, we reviewed 63 needle biopsies of the prostate containing a total of 75 foci of adenosis. Of the 63 cases, 51 (81%) were seen in consultation by one of the authors, and in approximately 80% of these cases, the differential diagnosis included low-grade adenocarcinoma. Crystalloids were present in 18 foci (24%), a minimally infiltrative growth pattern in 10 foci (13%), prominent nucleoli in 10 foci (13%), scattered single cells in eight foci (11%), mitoses in two foci (3%), and blue-tinged muci-nous secretions in two foci (3%). Immunohistochemistry was performed on 29 (39%) foci to rule out adenocarcinoma. Intraluminal crystalloids, a minimally invasive growth pattern, and single cells occur with sufficient frequency in adenosis, such that their presence is not useful in distinguishing low-grade adenocarcinoma from adenosis; 62 (83%) of the foci of adenosis were found to contain none of the remaining histologic features (mitoses, blue-tinged luminal secretions, prominent nucleoli), whereas 12 foci (16%) had one of the features and one focus (1%) had two features. Adenosis should always be in the differential diagnosis when one is considering low-grade carcinoma on needle biopsy. The key feature of adenosis is the merging of small crowded glands with surrounding benign glands; in contrast, the small glands of adenocarcinoma differ in their cytoplasm, nuclei, or luminal contents from adjacent benign glands. PMID- 7793474 TI - Low-stage clear-cell carcinoma of the endometrium. AB - Clear-cell carcinoma (CCC) of the endometrium is a relatively rare malignancy that is considered to be one of the most aggressive types of endometrial carcinoma. To evaluate the behavior of low-stage (stages I and II) CCC of the endometrium, we retrospectively reviewed 17 such cases seen at The University of Texas M.D. Anderson Cancer Center from 1963 to 1990. Patients' ages ranged from 52 to 81 years. Fifteen cases were pure CCC, and two cases were predominantly CCC with a focus of endometrioid adenocarcinoma FIGO grade I. All patients have been followed-up for at least 3 years. At the time of the study, six patients were alive without disease, one patient was alive with disease, five had died of other causes, and five had died of disease. The estimated survival rate was 71%. Estimated 5-year survival rates for endometrioid adenocarcinoma FIGO grade III and uterine papillary serous carcinoma are 73 and 39%, respectively. We conclude that patients with low-stage CCC of the endometrium have a survival rate similar to that of patients with endometrioid adenocarcinoma FIGO grade III and better than that of patients with uterine papillary serous carcinoma of similar stages. PMID- 7793475 TI - Fibrous dysplasia and cemento-ossifying fibroma. A histologic spectrum. AB - Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are benign fibro osseous lesions that are generally considered to be separate entities, distinguished by histologic and radiographic features. In our experience, some lesions lack the classic clinical, radiographic, or pathologic features of FD or COF and rather have overlapping features of both entities. Consequently, these cases are frequently diagnosed nonspecifically as fibro-osseous lesions. We examined 56 gnathic and extragnathic fibro-osseous lesions of bone morphologically, clinically, and radiographically to determine whether they can be reliably distinguished and whether their distinction has any clinical or prognostic significance. The lesions exhibited a broad morphologic spectrum of patterns ranging from pure FD (24 cases) to pure COF (10 cases). Twenty-two lesions contained a mixture of both patterns; 11 lesions with a predominant FD pattern contained calcified spherules histologically indistinguishable from those characteristically seen in COF. The remaining 11 lesions contained areas of typical FD adjacent to areas of COF. The lesions examined also demonstrated considerable radiographic overlap, and FD could not be reliably distinguished from COF. The recurrence rate was low for all lesions regardless of the histologic pattern. Because of histologic and radiographic overlap and similar low recurrence rate of FD and COF, we consider them to be related lesions, and COF is probably an opposing end of a morphologic spectrum of FD. PMID- 7793476 TI - Liposarcoma of the anterior mediastinum and thymus. A clinicopathologic study of 28 cases. AB - We studied 28 cases of anterior mediastinal liposarcoma occurring in 16 males and 12 females with a mean age of 43 years (range, 14-72). Presenting symptoms included dyspnea (four cases) and chest pain (four cases), although 11 tumors were detected incidentally by routine chest radiography. Seven cases were believed to be located within the thymus. Most (i.e., 25) of the cases were of low grade, with the well-differentiated lipoma-like or sclerosing subtypes constituting 60% and the myxoid subtype constituting 28%; the remaining 12% exhibited mixed features. Three cases were pleomorphic type. Several low-grade tumors exhibited widespread, dense aggregates of mature-appearing lymphocytes and plasma cells, which occasionally obscured the mesenchymal nature of the neoplasm, suggesting instead a lymphoid neoplasm or a reactive fibroinflammatory condition. The three high-grade tumors showed combinations of pleomorphic and round cell patterns, with focal myxoid areas. Of the cases grossly arising within the thymus, only one showed extensive thymic tissue within the lesion ("thymoliposarcoma"); six others exhibited residual thymus peripheral to the tumor. Clinical follow-up in 23 cases revealed recurrence in seven patients (31.8%), with a mean interval to recurrence of 3 years. Eight patients died (mean survival, 2.6 years), one postoperatively and three following a recurrence. Fifteen patients were alive (mean survival, 2 years), four with recurrent tumor. The myxoid tumors had a somewhat more aggressive course than the well differentiated tumors. Metastases were not observed in any of the patients. PMID- 7793477 TI - Pagetoid melanocytosis. Histologic features in benign and malignant lesions. AB - Pagetoid melanocytosis (PM), the upward discontinuous extension of melanocytes into the superficial epidermis, although generally considered a histologic feature of malignancy, may be seen in certain benign melanocytic lesions. To formulate the histologic criteria for distinction between benign and malignant PM, we examined 218 melanocytic tumors, including melanomas, Spitz nevi, nevi of palms and soles, pigmented spindle cell nevi, recurrent nevi, vulvar nevi, nevi of infancy and early childhood, and ordinary acquired nevi. We found PM to be present in 96% of melanomas, 38% of Spitz nevi, 61% of nevi of palms and soles, 20% of pigmented spindle cell nevi, 60% of recurrent nevi, 80% of vulvar nevi, and none of the ordinary acquired nevi. All the nevi of infancy and early childhood showed PM, but they had been selected for that feature. In melanomas, PM showed significant cellular atypia (81%), which was extensive and diffuse, and in 13% it extended laterally beyond the underlying junctional component. In the benign lesions, cellular atypia was generally absent, nor was lateral extension present, and PM was usually focal or multifocal rather than diffuse and not extensive. Although PM should be considered a tocsin for malignant melanoma, it may also occur in certain benign melanocytic lesions. Accurate interpretation depends on evaluation of all of the pertinent histologic and clinical findings. PMID- 7793478 TI - Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. AB - We conducted a clinicopathologic study of 79 cases of Kikuchi's disease. Our results confirmed that Kikuchi's disease is a distinctive type of necrotizing lymphadenitis that affects primarily the cervical lymph nodes of young adults and has a self-limited clinical course. However, female predominance was not as striking as heretofore reported. A low, but possible, recurrence rate of 3.3% was documented. Extranodal cutaneous involvement occurred in one patient who had a more severe and protracted clinical course. Classification of the histopathologic changes into three histologic types was proposed: proliferative, necrotizing, and xanthomatous types. These three types differed in certain aspects of their clinical features. Immunohistologic analysis revealed that the predominant cells of the lesions were various types of histiocytes, including the enigmatic plasmacytoid monocytes. A variable number of CD8(+) T cells correlating with the duration of the disease was detected. B cells were nearly absent, and only an insignificant number of OPD4(+) T cells was present. Eight cases studied by the flow cytometric DNA analysis all showed a diploid DNA content. Although the histologic changes of Kikuchi's disease were variable, the findings were sufficiently distinctive to permit accurate diagnosis. Malignant lymphoma and especially lupus lymphadenitis can be mistaken for Kikuchi's disease; thus differentiation is crucial. PMID- 7793479 TI - Papillary Hurthle cell carcinoma with lymphocytic stroma. "Warthin-like tumor" of the thyroid. AB - We report 13 cases of a peculiar thyroid tumor of follicular epithelial differentiation with distinctly papillary architecture, oxyphilic cytology, and lymphocytic infiltrates in papillary stalks. The majority of these tumors arose in glands with chronic lymphocytic thyroiditis. The combination of oxyphilic cells and lymphocytic stroma gives these tumors a startling resemblance to papillary cystadenoma lymphomatosum, or "Warthin's tumor" of the salivary gland. Twelve tumors occurred in women (age range: 26-66 years, mean 44 years). Two tumors were in the isthmus, six in the right lobe, and four in the left lobe. The only man, 34 years old, had multiple bilateral tumor nodules. The lesions ranged from 0.3 cm to 3.5 cm in maximum dimension. The largest lesion, in a 58-year-old woman, infiltrated skeletal muscle. Three other patients had lymph node metastases, while the nine remaining tumors were confined to the thyroid. Follow up in these cases suggests that although the histological appearance of these neoplasms is unusual, they behave as typical papillary carcinomas. The striking lymphocytic infiltration and oxyphilic metaplasia in these tumors as well as the association with chronic lymphocytic thyroiditis suggest that as yet undefined immunological mechanisms may play a role in the pathogenesis of this disorder. PMID- 7793480 TI - Malignant mesothelioma of the tunica vaginalis. A clinicopathologic analysis of 11 cases with review of the literature. AB - Eleven malignant mesotheliomas of the testicular tunica vaginalis occurred in patients aged 12 to 76 (mean, 54.1) years. Hydrocele, with or without an associated mass, or appreciation of a paratesticular mass accounted for the clinical presentation. One patient had a history of asbestos exposure. Grossly, the tumors typically presented as multiple nodules studding a hydrocele sac, frequently associated with a mass infiltrating the spermatic cord or adjacent testis. Microscopically, five tumors were epithelial and six biphasic, with the typical architectural and cytologic features of mesothelioma. Mixtures of papillary, tubular, and solid patterns predominated in the epithelial areas; interlacing fascicles of spindle cells with scanty stroma characterized the sarcomatous components. All eight of the tumors that were stained for keratin (AE1/AE3) were positive, four of five for epithelial membrane antigen, and four of five for vimentin. Seven of seven tumors were carcinoembryonic antigen negative and five of five B72.3, Leu-M1, and Ber-Ep4 negative. Follow-up ranging from 1 to 15 (mean, 4.3) years was available for seven patients. Three died of disease after 4, 4, and 3 years, and three are alive with disease 2, 2, and 15 years after diagnosis. Two of the latter three patients had extensive local recurrences, one 15 years after the diagnosis of a well-differentiated papillary mesothelioma, the other 2 years following treatment with hydrocelectomy only. One patient who has been followed for only 1 year has no evidence of disease. This series emphasizes a number of important features of testicular mesothelioma; (a) a wide age range with occasional occurrence at a young age, (b) a wide morphologic spectrum with regard to degree of differentiation, and (c) an aggressive natural history with a potential for late recurrence or metastasis of even well-differentiated tumors, suggesting the need for initial aggressive surgical treatment. PMID- 7793481 TI - Mucoepidermoid carcinomas of the thymus. A clinicopathologic study of six cases. AB - Six cases of mucoepidermoid carcinoma of the thymus are presented. The patients were two men and four women aged 17 to 66 years (median age, 34.5). Clinically, three patients had symptoms of chest discomfort and three were asymptomatic. Grossly, the tumors in three patients were described as cystic structures varying in size from 7 to 8 cm in greatest dimension, with focal areas of induration within the walls of the cyst that averaged from 1.5 to 3 cm. The other three cases had grossly and radiographically well-circumscribed, homogeneous tumor masses. Histologically, the lesions showed a spectrum of features that ranged from those of well-differentiated, to moderately well-differentiated, to poorly differentiated mucoepidermoid carcinoma, with sheets and solid islands of squamoid cells admixed with mucin-secreting epithelium lining gland-like spaces. In four cases, the tumor was histologically seen in continuity with the epithelial lining of multilocular cystic structures; the nonneoplastic components of the cysts contained abundant inflammation and showed the features of otherwise conventional acquired multilocular thymic cysts. Clinical follow-up showed that the two patients with intermediate and high-grade tumors died within 2 and 7 months after initial diagnosis. One of these patients showed at autopsy residual tumor limited to the mediastinum, whereas the other patient died with metastases to pericardium and myocardium despite postoperative radiation therapy. Two patients with low-grade tumors were alive and well with no residual disease 2 and 3 years after surgery, and the other two were lost to follow-up. Mucoepidermoid carcinoma of the thymus should be included in the differential diagnosis of cystic neoplasms of the thymus. As with their counterparts at other sites, the biologic behavior of these tumors closely correlates with their degree of differentiation and amount of cytologic atypia. PMID- 7793482 TI - Carcinoma of the thymus with clear-cell features. Report of eight cases and review of the literature. AB - We report eight cases of thymic carcinoma with clear-cell features and review the five previously reported cases. The tumor was composed of cells with clear cytoplasm and rather bland nuclear features, and showed a lobular or occasionally sheet-like growth pattern. Cytoplasmic glycogen was demonstrable in 92% of cases, whereas mucin was absent in all cases tested. The tumor cells were uniformly immunoreactive for low- and high-molecular-weight keratins and were reactive for epithelial membrane antigen in 22% of cases. The differential diagnosis includes mediastinal seminoma, parathyroid carcinoma, and metastatic clear-cell carcinoma. The diagnosis of primary thymic carcinoma depends on the exclusion of other primary sites clinically, particularly lung and kidney, and the demonstration of postivity for keratins and negativity for placental alkaline phosphatase. Thymic carcinoma with clear-cell features behaves as a high-grade thymic carcinoma: including our cases and the previously reported cases, nine of 13 patients (69%) are either dead of disease or have persistent disease at the latest follow-up. The importance of this entity is recognition of its aggressive clinical behavior and its distinction from other primary and metastatic clear-cell neoplasms of the mediastinum. PMID- 7793483 TI - Clarifying statements on T-cell-rich B-cell lymphomas. PMID- 7793484 TI - MAb O13. PMID- 7793485 TI - A critical appraisal of the small-diameter portacaval H-graft. AB - BACKGROUND: The ideal portasystemic shunt should prevent variceal hemorrhage and preserve portal flow to reduce hepatic encephalopathy. The partial shunting proposed by Sarfeh effectively controls variceal bleeding while preserving prograde hepatic portal flow. PATIENTS AND METHODS: We analyzed results of the partial portacaval shunt prospectively in 43 patients undergoing small-diameter (8-mm or 10-mm) portacaval H-graft. Patients entered into the study had Child Pugh class A and class B cirrhosis, and all had documented previous variceal hemorrhages. We used the Sarfeh technique without performing portal collateral ligation. RESULTS: Operative mortality was 5%. Acute graft thrombosis occurred in 3 patients, 2 of whom were successfully lysed by urokinase infusion angiographically, while later graft occlusion occurred in 1 case. Only 1 patient rebled from varices in our late follow-up (14 to 65 months). Prograde portal flow was maintained in 90% of patients undergoing repeat angiography 27 +/- 13 months postoperatively. The incidence of all encephalopathy episodes was 16%, with only 1 patient having this complication chronically. CONCLUSIONS: The small-diameter portacaval H-graft of Sarfeh is an effective operation for controlling variceal hemorrhage. It preserves hepatic portal perfusion over time in the majority of patients, reducing the risk of encephalopathy. The procedure may be particularly suited for alcoholic cirrhotic patients with less advanced liver disease. PMID- 7793486 TI - Polypropylene mesh closure of the complicated abdominal wound. AB - BACKGROUND: Closure of the abdominal wall in the face of fascial necrosis or massive intestinal edema remains a difficult problem with frequent complications. Prior studies have addressed both the utility and the pitfalls of placing polypropylene mesh in this setting. METHODS: We performed a retrospective evaluation of our experience with polypropylene mesh in traumatic and nontraumatic difficult abdominal closures. Timing of mesh placement and removal relative to the initial operation were recorded, as were abdominal complications, number of operative procedures, and type of ultimate abdominal closure. RESULTS: Between 1988 and 1993, polypropylene mesh was placed in 26 critically ill or injured patients requiring celiotomy, of whom 23 survived more than 3 weeks. Ultimate wound management was delayed mesh removal and primary closure (17%), myocutaneous flap coverage over mesh (4%), split-thickness skin grafting to the granulating wound (35%), or closure by secondary intention over mesh (43%). Split thickness skin grafting and closure by secondary intention resulted in enterocutaneous fistulas in 50% and 40% of cases, respectively. Full-thickness closure with or without mesh removal resulted in no fistulas. CONCLUSION: Mesh provided adequate fascial closure, even with gross wound contamination. Coverage of polypropylene mesh by secondary intention or split-thickness skin grafting resulted in unacceptably high rates of fistulous complications, and this procedure should be replaced by either mesh removal or full-thickness coverage. PMID- 7793488 TI - Psychoneuroimmunology: a new fad or the fifth cancer treatment modality? PMID- 7793487 TI - A prospective multicenter evaluation of preoperative hemostatic screening tests. The French Associations for Surgical Research. AB - BACKGROUND: Several retrospective and four prospective reports have questioned the need for routine preoperative hemostatic screening tests (PHST) in general surgery. PATIENTS AND METHODS: The results of four standard tests (prothrombin time, activated partial thromboplastin time, platelet count, and bleeding time) were prospectively compared with patient history and clinical data in a multicenter study of 3,242 consecutive patients. The patients were divided into four groups: group A (n = 1,951) had no clinical or PHST abnormalities; group B (n = 340) had no clinical and one or more PHST abnormalities; group C (n = 779) had one or more clinical and no PHST abnormalities; group D (n = 172) had both clinical and PHST abnormalities. RESULTS: Preoperative modifications of guidelines (postponed operations and ordering of additional hemostatic tests) were significantly more frequent in both groups of patients with PHST abnormalities (groups B and D), but specific treatment to correct hemostatic disorders was prescribed only when clinical abnormalities were also present (group D). Intraoperatively, modifications of anesthetic and surgical vigilance (planning of increased number of blood units, vascular catheter placement, and number of patients requiring transfusion) were significantly more frequent in group D. Postoperatively, all groups had similar incidences of hematoma or bruises, volumes of blood loss per drainage, reoperations to control hemorrhage, and mortality due to bleeding (n = 5). CONCLUSIONS: Our results suggest that PHST should not be performed routinely, but only in patients with abnormal clinical data. Such a policy necessitates a thorough history--including answers to a specific questionnaire like those used in prospective studies--and a rigorous, well-conducted physical examination. PMID- 7793489 TI - Unilateral breast masses in men over 40: a diagnostic dilemma. AB - BACKGROUND: Breast enlargement in men is a common condition with advancing age. The main problem in this age group is to differentiate gynecomastia or benign enlargement from carcinoma. PATIENTS AND METHODS: Over a 14-year period, 60 patients > or = 40 years old were operated on four unilateral breast masses (11 carcinoma, 49 gynecomastia) at the University College Hospital, Galway, Ireland. The medical records of these patients were reviewed and data were collected from patients' charts and histopathology records. RESULTS: Patients with carcinoma delayed significantly longer before presentation than patients with gynecomastia, a median of 33 versus 3.4 months, respectively. A lump was the presenting complaint in patients with carcinoma unless the disease was advanced. Patients with gynecomastia were more likely to present with pain; and the majority of these patients described tenderness on clinical examination. A history of carcinoma (18% and 0%) or a family history of breast carcinoma (36% and 14%) was more common in the patients with carcinoma than in those with gynecomastia, respectively (P < 0.05; P = NS, respectively). Histories of consuming alcohol and smoking cigarettes were more common in those with gynecomastia (67% and 43%) than in those with carcinoma (55% and 18%). A similar proportion of patients in both groups were taking drugs known or suspected to cause gynecomastia (29% and 27%). CONCLUSIONS: Carcinoma must be excluded in patients presenting with unilateral breast masses, particularly in those patients who present with painless masses. Clues to the diagnosis are provided by a history of carcinoma or a family history of breast carcinoma. A history of consumption of drugs known to cause gynecomastia should not influence the decision to perform a biopsy on unilateral breast masses in older men. PMID- 7793490 TI - A comprehensive characterization of lymphoepithelial cyst associated with the pancreas. AB - BACKGROUND: Lymphoepithelial cyst of the pancreas is a rare but distinctive cystic lesion lined by a mature, keratinizing squamous epithelium and surrounded by lymphoid tissue. METHODS: To gain more insights into this entity, we describe 5 examples of lymphoepithelial cyst of the pancreas (2 of which were briefly described before) and compare them with similar cases in the literature for a total of 19 cases. RESULTS: The male:female ratio was 16:3; patients' ages ranged from 32 to 73 years (mean and median 51). The lymphoepithelial cyst was incidentally found at autopsy in 4 patients (21%) or during evaluation for unrelated diseases in another 4 patients (21%). In the remaining 11 patients, the cyst was associated with abdominal pain in 9 (47% of all patients), nausea/vomiting in 3 (16%), diarrhea in 1 (5%), and nonspecific systemic symptoms in 6 (32%) (some patients had more than 1 associated symptom). Computed axial tomography scan, with or without ultrasonographic study, was done in 16 cases and uniformly displayed a single, well-circumscribed, cystic mass protruding beyond the surface of the pancreas; the rest of the pancreas was normal. Intraoperatively, the cyst was readily apparent once the lesser sac was entered and the surface of the pancreas exposed; the cyst was located at the head (3 cases), neck (1 case), body (6 cases), and tail (9 cases). Surgery was done for all 15 clinical cases and included local excision of the cyst with a thin rim of attached, underlying pancreas (6 cases), or distal pancreatectomy with (4 cases) or without (3 cases) splenectomy. Follow-up information, available in 7 cases, showed that all symptoms disappeared and the patients were alive and well up to 6 years after surgery. CONCLUSIONS: This rare cyst of the pancreas has a uniform and characteristic clinicopathologic profile, enabling easy and accurate diagnosis. Although the histogenesis of lymphoepithelial cysts is not known, they are benign and can be cured by local excision. PMID- 7793492 TI - Predicting common bile duct lithiasis: determination and prospective validation of a model predicting low risk. AB - BACKGROUND: The aim of this two-part prospective study was: (1) to identify simple, noninvasive, preoperative factors associated with low or very low risk of common bile duct lithiasis (CBDL); and (2) to test the validity of the statistical model obtained during Part One by the postcholecystectomy follow-up of patients classified into a low-risk group. PATIENTS AND METHODS: In Part One of the study, preoperative clinical, biologic, and ultrasonographic data, and intraoperative cholangiographic findings were collected from 503 consecutive patients undergoing cholecystectomy for symptomatic lithiasis from 1985 to 1989. Using the data obtained in Part One, a linear logistic model was used prospectively in Part Two to determine the prediction of absence of CBDL in 279 consecutive patients. No jaundice, normal transaminase levels, common bile duct (CBD) diameter < 8 mm, and no intrahepatic duct enlargement defined the low-risk group of CBDL. RESULTS: In Part One, CBDL was present in 84 (17%) of all patients. Five parameters were used to classify 73% of all patients as low risk of CBDL and 27% as high risk. In the low-risk groups, CBDL was present in 1% of 116 cases with acute gallbladder complications, and 5% of 250 cases with no acute gallbladder complications. In Part Two, 171 (61%) patients were classified in the low-risk group (Group 1), and CBD stones were not sought by any additional preoperative investigations or intraoperative cholangiography (IOC). One hundred eight patients (39%) were considered at risk of CBDL (Group 2). Mean follow-up was 20.6 months (median 19); 2 patients (1%) in the low-risk group presented a symptomatic retained stone. CONCLUSIONS: This study validated this simple model for predicting risk of CBDL and avoiding invasive preoperative investigations--as well as IOC--in more than 60% of symptomatic cholelithiases. In addition, this model seemed useful for defining patients in whom further exploration for CBDL was justified, since 42 (39%) of the 108 Group 2 patients were proved to have CBDL. PMID- 7793491 TI - Anomalies at the thoracic outlet are frequent in the general population. AB - BACKGROUND: Abnormal anatomy at the thoracic outlet is frequent in patients operated on for thoracic outlet syndrome (TOS). The present study was designed to find out the rate of thoracic outlet anomalies in the general population. METHODS: Fifty cadavers representing a general population were subjected to a total of 98 meticulously performed cervical dissections to ascertain the frequency of congenital anomalies in the thoracocervicoaxillary region. RESULTS: During the 98 cervical dissections, 62 instances of abnormal anatomy of the thoracic outlet were found, and fully normal anatomy was found in 36 cases. Of the total 69 abnormalies, 66 could be classified according to Roos: 37 were type 3 abnormalities, 15 were type 5, 9 were type 11, and there was 1 each of type 4, type 6, type 7, type 9, and type 10 abnormalities. The remaining 3 abnormalities did not fit into Roos' classification. Only 10% (5/50) of the cadavers had a bilaterally normal anatomy. CONCLUSIONS: The results demonstrate that abnormal structures, such as congenital bands in the thoracic outlet, are more common in the general population than had previously been described. We suggest that fibrous bands confer a predisposition for TOS following a certain degree of stress or injury. PMID- 7793493 TI - Classification and treatment of local septic complications in acute pancreatitis. AB - BACKGROUND: An international symposium on acute pancreatitis recently developed a clinical classification system for severe acute pancreatitis that classifies all local septic complications into three groups: infected necrosis (IN), sterile necrosis (SN), and pancreatic abscess (PA). Despite the appeal of having three distinct, well-defined labels for this complex process, the clinical utility of this schema has yet to be determined. The purpose of this study was to investigate the prognostic and therapeutic utility of applying this clinical classification system to a large group of surgical patients with local septic complication from acute pancreatitis. PATIENTS AND METHODS: We reviewed the cases of 62 patients with complicated pancreatitis, classifying them into IN (n = 20), SN (n = 14), or PA (n = 28) groups. Ranson's score, APACHE II score, and computed tomography grading were calculated within the first 48 hours of admission. Information on patient demographics, etiology of pancreatitis, operative procedures, timing of intervention, bacteriology, blood loss, intensive care unit days, ventilator days, and morbidity and mortality were also accrued and analyzed. RESULTS: Despite similar demographics and etiology of pancreatitis, patients with necrosis, both IN and SN, were more critically ill than were patients with PA (APACHE II score > 15, 21% versus 0%, respectively), required earlier operative intervention (mean 14 days versus 29 days, P = 0.02), required necrosectomy with drainage (65% versus 4%, P < 0.001) rather than simple drainage (3% versus 86%, P < 0.001), more reoperations (2.3 versus 1.1, P < 0.05), and had a significantly higher mortality rate (35% versus 4%, P < 0.05). In addition, patients with IN required significantly more hospital days, ventilator days, and blood transfusions than either patients with SN or PA (P < 0.05). CONCLUSIONS: We conclude that this classification system allows for the stratification of patients into three distinct groups--infected necrosis, sterile necrosis, and pancreatic abscess--and has both therapeutic and prognostic usefulness. PMID- 7793494 TI - Pitfalls in the diagnosis of blunt diaphragmatic injury. AB - BACKGROUND: Severe blunt trauma to the torso can result in diaphragmatic disruption. Prompt recognition of this potentially life-threatening injury is difficult when the initial chest roentgenogram is unrevealing and immediate thoracotomy or celiotomy is not performed. This retrospective study was undertaken to: (1) determine the incidence of missed diaphragmatic injuries on initial evaluation; (2) identify factors contributing to diagnostic delays; and (3) formulate a diagnostic approach that reliably detects diaphragmatic rupture following blunt trauma. METHODS: Retrospective review of hospital records and radiographs from our 18-year experience with blunt diaphragmatic injuries. RESULTS: Seven of 57 (12%) blunt diaphragmatic injuries were missed on initial evaluation. Recognition followed 2 days to 3 months later. Two (4%) isolated left sided injuries initially presented with normal chest roentgenograms. Five patients (9%) (4 with right-sided ruptures) had abnormalities on chest roentgenogram or computed tomography (CT) initially attributed to chest trauma. They were diagnosed by radionuclide, ultrasound, or CT investigations of hemothorax, pulmonary sepsis, and right upper quadrant pain; and, in 1 case, at thoracotomy for a persistent right hemothorax. In the remaining 50 patients (88%), the diagnosis was established within 24 hours. In 21 (42%) of these, the problem was initially recognized at the time of celiotomy for accompanying injuries. CONCLUSIONS: Blunt diaphragmatic injuries are easily missed in the absence of other indications for immediate surgery, since radiologic abnormalities of the diaphragm--particularly those involving the right hemidiaphragm--are often interpreted as thoracic trauma. In this setting, a high index of suspicion coupled with selective use of radionuclide scanning, ultrasound, and CT or magnetic resonance imaging is necessary for early detection of this uncommon injury. PMID- 7793496 TI - The learning curve for laparoscopic cholecystectomy. The Southern Surgeons Club. AB - BACKGROUND: The use of laparoscopic surgical procedures without previous training has grown rapidly. At the same time, there have been allegations of increased complications among less experienced surgeons. METHODS: Using multivariate regression analyses, we evaluated the relationship between bile duct injury rate and experience with laparoscopic cholecystectomy for surgeons in the Southern Surgeons Club. RESULTS: Fifty-five surgeons performed 8,839 procedures. Fifteen bile duct injuries (by 13 surgeons) resulted with 90% of the injuries occurring within the first 30 cases performed by an individual surgeon. Multivariate analyses indicated that the only significant factor associated with an adverse outcome was the surgeon's experience with the procedure. A regression model predicted that a surgeon had a 1.7% chance of a bile duct injury occurring in the first case and a 0.17% chance of a bile duct injury at the 50th case. CONCLUSIONS: While surgeons appear to learn this procedure rapidly, institutions might consider requiring surgeons to move beyond the initial learning curve before awarding privileges. PMID- 7793497 TI - A salvage technique for continuous ambulatory peritoneal dialysis catheters with exit-site infections. AB - Catheter infection is a major complication of continuous ambulatory peritoneal dialysis (CAPD) therapy for end-stage renal disease. Catheter exist-site infections were treated with a new surgical technique consisting of dissection and removal of the existing catheter in the subcutaneous layer, insertion of a catheter connector and new catheter piece, and creation of a new subcutaneous tunnel. The new surgery can be performed on an outpatient basis and allows for the continuation of CAPD, thereby avoiding the cost associated with inpatient admission and interim hemodialysis. PMID- 7793495 TI - Reappraisal of safety of endoscopic sphincterotomy for common bile duct stones in the elderly. AB - BACKGROUND: Endoscopic sphincterotomy is the method of choice for elderly patients with common bile duct stones, even though these patients are poor operative risks. We undertook this study to analyze the operative risk factors for this age group. METHODS: We compared specific problems of 182 patients aged 80 years or older and 921 younger patients who underwent endoscopic sphincterotomy for common bile duct stones. RESULTS: Despite a higher frequency of periampullary diverticula in the elderly than in the younger patients (54% versus 36%, P < 0.001), the success rates of sphincterotomy were not different. The elderly patients required lithotripsy more often than did the younger ones (15% versus 4%, P < 0.001), and the necessity of stenting or nasobiliary drainage was greater in this group (9%) than in the younger group (5%, P < 0.05). This difference in the tactics between the older and younger groups was due to the greater number and size of stones, longer period of time for complete clearance of the common bile duct (13.5 versus 6.0 days, P < 0.01), and a greater percentage of patients with operative risks (55% versus 36%, P < 0.001). The elderly also had significantly greater overall morbidity compared with the younger patients (13% versus 7%, P < 0.005), frequency of acute cholangitis (8% versus 2%, P < 0.001), and mortality (1% versus 0%). CONCLUSION: These results suggest that frequent stenting or nasobiliary drainage to prevent cholangitis or prompt stone removal by lithotripsy would be necessary in this group of patients. PMID- 7793498 TI - A technique for laparoscopic repair of herniation of the anterior abdominal wall using a composite mesh prosthesis. AB - Improved laparoscopic techniques have engendered many new gastrointestinal and other intracavity abdominal procedures. Groin hernias have also been repaired with the assistance of the laparoscope via both transperitoneal and properitoneal approaches, but less emphasis has been placed upon repair of hernias of the anterior abdominal wall. A technique for the transperitoneal, laparoscopic repair of anterior abdominal wall hernias using a composite mesh prosthesis is presented. The technique is applicable to hernias in many locations. PMID- 7793500 TI - Obturator hernia needs a laparotomy, not a diagnosis. AB - The obturator hernia is rare, accounting for only 0.05% of all hernias and 0.2% of all small-bowel obstructions requiring laparotomy at our institution. Typically, there is a delay in diagnosis and surgical intervention, despite the presence of a bowel obstruction. A laparotomy is needed, not a preoperative diagnosis. PMID- 7793499 TI - Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat. AB - BACKGROUND: Increased expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-1 (LFA-1) has been reported to play a major role in reperfusion injury after ischemia. In the present study we tested the effects of anti-rat-ICAM-1 monoclonal antibody (1A29) on partial-liver warm ischemia in rats. METHODS: Histological changes and expression of ICAM-1 and LFA 1 were investigated in rat partial-liver warm ischemia, performed by clamping hepatic hilar vessels distributing to the right lateral lobe for 30, 45, and 60 minutes. In a second study, the effects of intraportal 1A29 injection after 60 minutes of warm ischemia in the rat were examined histologically. In both studies, the liver tissue was removed for analysis 48 hours after clamping. RESULTS: Reperfusion after 60 minutes of warm ischemia induced histological liver injury and strong expression of ICAM-1 and LFA-1, although 30 and 45 minutes of ischemia did not provoke either histological damages or the expression of ICAM-1 and LFA-1. Intraportal injection of 1A29 after 60 minutes of warm ischemia clearly suppressed liver cell injury histologically. CONCLUSION: Intraportal injection of 1A29 prevented the histological inflammation of an ischemic liver and may be useful in liver surgery or liver transplantation, because high concentrations can reach the target organ and nonspecific immunosuppression in other tissues and organs can be decreased. PMID- 7793501 TI - Diagnosis and management of malignant pleural effusions. AB - Approximately half of all patients with metastatic cancer develop malignant pleural effusions. Because the patients are already terminally ill, these effusions can present significant diagnostic and therapeutic challenges. Symptoms are either present at the time of diagnosis or develop subsequently in virtually all cases. The diagnosis is based on chest radiography followed by thoracentesis or thoracoscopy. Most malignant effusions are exudative and about one third are bloody. Cytology is positive for cancer cells in the initial pleural fluid specimens from 60% of patients who are ultimately shown to have malignant effusions. The remaining 40% require a repeat thoracentesis, pleural biopsy, thoracoscopy, or multiple procedures to prove the presence of cancer. Because the average life expectancy of a patient with a malignant pleural effusion is about 6 months, it is important to obtain a diagnosis expeditiously and formulate a treatment plan that optimizes quality of life. Tube thoracostomy with chemical pleurodesis using doxycycline or bleomycin is the mainstay of current treatment and is about 85% effective. PMID- 7793503 TI - Alternate hemihepatic vascular control for hepatic resection. PMID- 7793502 TI - Transplantation of keratinocytes in the treatment of wounds. AB - BACKGROUND: Keratinocyte grafting can be used to treat acute traumatic and chronic non-healing wounds. The keratinocyte sheets are fragile and clinical "take" is difficult to assess, especially as activated keratinocytes secrete many growth factors, which have effects on wound healing apart from take. We have developed animal models of grafting that allow us to examine factors influencing autologous keratinocyte graft take. Results show clearly that pretreatment of the wound bed with viable dermis greatly increases the take of keratinocyte grafts. DATA SOURCES: International literature. CONCLUSIONS: As a greater understanding of the complex interactions of cell and matrix evolve, so will potential therapeutic maneuvers, not just in the field of cultured keratinocyte grafts, but clearly in that of benign tumors, for example, keloids, and that of oncology. There is now overwhelming evidence of the requirement for a dermal substitute for cultured keratinocyte autografts, and the sheet complexity of the situation demands that this should approximate live human dermis as closely as possible. The stumbling blocks relate to avoiding the risks of viral transmission, tissue matching of host and donor, providing early epithelial cover, and improving delivery systems for fragile keratinocyte grafts. PMID- 7793504 TI - Prognostic factors in paranasal sinus cancer. AB - PURPOSE: This study was designed to evaluate the influence of several different prognostic factors in determining both local recurrence rates and survival in patients treated for carcinoma of the paranasal sinuses. MATERIALS AND METHODS: A retrospective study of patients treated between January, 1975 and December, 1991 was undertaken. Hospital charts were reviewed collecting demographic, clinical, and radiographic findings, which were correlated with treatment and subsequent follow-up. RESULTS: Carcinoma of the paranasal sinuses was identified in 129 patients. This included 95 men and 34 women with an average of 59 years. The ethmoid sinus was primarily involved in 50 patients, the maxillary sinus and 49, the nasal sinus and 25, sphenoid sinus in three in the frontal sinus and two patients. Advanced stage (T3/T4) was diagnosed in 60% of patients at presentation. The most commonly encountered histologies were squamous-cell carcinoma and adenocarcinoma. The most accurate predictors of poor prognosis were advanced T stage and involvement of the anterior skill base. Involvement of the posterior wall of the maxillary sinus, infratemporal fossa, and erosion of the orbital wall was not associated with the worst prognosis. CONCLUSION: In spite of advances in imaging technique and surgical therapy, the primary cause of death is inability to control local disease. Diagnosis at an earlier stage is associated with improved outcome. PMID- 7793506 TI - Wegener's granulomatosis of the orbit: lacrimal gland involvement as a major sign. PMID- 7793505 TI - Adenosquamous carcinoma of the larynx. PMID- 7793507 TI - Hydatic cyst in the head and neck area. PMID- 7793508 TI - Laryngeal chondrosarcoma: two unusual cases. AB - Although CS is the most common mesenchymal tumor of the larynx, there have only been approximately 200 cases reported to date. The nature, diagnosis, and management of these tumors are discussed. Although conservative therapy is acceptable in most instances, total laryngectomy may be opted for in cases of extensive tumor, high-grade lesions, and recurrences. CO2 laser excision for palliation has been shown to be a viable alternative in patients with high operative risk. It is also shown that the behavior of these tumors is predictable, though not without some variation. Although these tumors are rare, CS must be considered when presented with a solid subglottic or neck mass. PMID- 7793509 TI - Imaging facial pain of trigeminal origin. PMID- 7793510 TI - Therapeutic embolization for control of epistaxis in a patient with hereditary hemorrhagic telangiectasia. AB - This article describes a woman with hemorrhagic telangiectasia, or Osler-Weber Rendu disease, with recurrent nosebleeds despite prior septal dermoplasty and laser treatments. Telangiectasias were clearly shown at the time of angiography. Embolization of abnormal vessels on both sides resulted in cessation of epistaxis for many months. Bilateral studies are important, even when the epistaxis seems to be unilateral. PMID- 7793511 TI - Medicine and art: facial palsy depicted in archaic Greek art on Crete. AB - A small earthenware statuette was evacuated from the votive-depot of acropolis of Gortys, an ancient town in South-Crete/Greece. This ex-voto is dated approximately 7th to 6th century BC and very probably represents some symptoms of a stroke, especially the left facial palsy and the contracture of the left arm. Since the Minoan time until today, people of Crete have been offering ex-votos to gods or saints to ask for help in specific diseases. PMID- 7793512 TI - The management of the lower eyelid in facial paralysis. PMID- 7793514 TI - [A parallel comparison between cytological and cervicographic screening in early pregnancy]. AB - The aim of this study is to compare the diagnostic possibilities of cytologic and cervicographic screening of the cervix uterus in patients with early pregnancy. Fifty-four patients between the ages of 20 and 37 were examined cytologically and cervicographically in a prospective screening study. The dependability of each of the diagnostic tests was measured histologically (with the patient's approval) using punch biopsy under colposcopic control. The histologic results showed the presence of CIN in 9 women (16.7%), 8 of them with CIN I and one with CIN III. The rest of examined patients (45) had normal of various inflammatory findings. The analysis of the obtained results confirm a statistically significant difference between the two diagnostic, screening methods. The cervicographic examination is considerably more sensitive in finding CIN-44.4% compared to 22.2% of the cytology. Whereas the cytological method has a higher specificity as a test in determining the healthy patients-91.1% versus 51.2% of the cervicography. 12 or 22.2% of the cervicograms were technically defective. PMID- 7793513 TI - Interleukin-8 gene expression in chronic sinusitis. AB - PURPOSE: Interleukin-8 (IL-8), a monocyte-derived and macrophage-derived cytokine, displays potent chemotactic activating properties toward neutrophils and thus may contribute to the pathogenesis of chronic sinusitis. The object of this investigation was to show the expression of the IL-8 gene in chronic sinusitis by Northern blot analysis and a reverse transcription-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: For Northern blot analysis, RNAs were extracted from maxillary mucosa and nasal polyps from two patients with chronic sinusitis, respectively, and from the inferior turbinate of a nasal allergy patient. For RT-PCR, RNAs were extracted from 11 patients with chronic sinusitis, 8 patients with allergic rhinitis, and 4 patients with hypertrophic rhinitis. RESULTS: Whereas IL-8 mRNA was expressed in the maxillary mucosa, IL-8 transcript was not detected in the inferior turbinate by Northern blot analysis. IL-8 transcripts were detected in 45% of chronic sinusitis RNAs (5/11) and in 50% of allergic rhinitis RNAs (5/10) by RT-PCR. CONCLUSION: These data suggest IL-8 may contribute to neutrophil involvement in chronic sinusitis. PMID- 7793515 TI - [An epidemic outbreak among newborn infants caused by rotaviruses]. AB - The authors describe a nosocomial infection of rotavirus gastroenteritis in a Neonatal Intensive Care Unit, which affect ten, mainly premature infants. A positive coproculture of rotavirus is isolated from 4 symptomatic and 4 asymptomatic infants. The leading syndrome is that of dehydration in 80% of the cases, attended by moderately expressed diarrhoea and vomitus. The main laboratory sign is marked metabolic acidosis in 80% of the patients. An effective pathogenetic therapy is implemented which eliminates the infection in 2 months without lethal exitus. PMID- 7793516 TI - [The current aspects of hospital infections in maternity and neonatal wards]. AB - The epidemiologic, etiologic and clinical structure of HAI in the maternity and neonatal wards in the country for the 1982-1992 period has been specified. 934 women in child-birth and 2357 neonates acquire nosocomial infections at an average annually. A comparatively constant level in HAI epidemic process intensity is observed with inconsiderable diversions in the beginning and by the end of the studied period. Staphylococci like causative agents of HAI take up a leading place in both types of wards with especially marked incidence rate among the newborn children. The predominant clinical forms in the women in child-birth are the surgical wound infections, skin and genital infections and in the neonates--the staphylodermatites, upper respiratory airway infections, pulmonary and enteric infections. PMID- 7793517 TI - [Genital chlamydial infection in women studied with the new Clearview Chlamydia diagnostic test]. AB - For the first time in Bulgaria a clinical investigation was carried out using the direct antigen test Clearview Chlamydia for the diagnosis of Chlamydia infection in gynaecologic patients 130 women were examined in whom chlamydial infection was suspected. 43 patients (out of 130) were positive. The conclusion of the study is that the clinical signs of female genital chlamydial infection are not specific and for the exact diagnosis a laboratory test for detecting Chlamydia trachomatis must be carried out. The new diagnostic test Clearview Chlamydia is easy and rapid to perform and could be very useful for the office practice. PMID- 7793518 TI - [The static and dynamic profiles of urethral pressure in women with stress incontinence and in healthy controls]. AB - The study presents the results of urethral pressure profile measurements in 3 groups of women: continent nulliparous, continent parous and stress incontinent women. The maximum urethral closure pressure, the functional urethral length and the length of continence zone are compared. The healthy control groups (both parous and nulliparous) show much higher maximum urethral closure pressures than those mentioned in literature. No difference is evident between continent parous and continent nulliparous which suggests that vaginal delivery at term does not necessarily impair urethral sphincteric function. On the other hand women with similar age and parity with stress incontinence have a marked decrease of maximum urethral closure pressure at rest and demonstrate inability to increase it by volitional contraction of the pelvic floor. These findings support the idea of the leading role of sphincteric incompetence in stress incontinence. The functional urethral length and the length of continence zone show no significant differences among the investigated groups which implies that they are of no importance for the occurrence of stress incontinence. PMID- 7793520 TI - [The potentials of computed axial tomography (CAT) in the diagnosis of carcinoma of the cervix uteri]. AB - 14 women with diagnosis Ca colli uteri Ib stage were investigated. CAT (computer axial tomography) was carried out before and after surgery (Wertheim). CAT gave a picture of the tumor lesion as well as of the regional lymph nodes. This method proved fast, efficient and non invasive for the correct diagnosis of Ca colli uteri and surgery effect. PMID- 7793519 TI - [Uterine sonography as a method for the early detection and screening of endometrial carcinoma in women in the postmenopause with and without diabetes mellitus]. AB - An attempt was made to examine the efficiency of the uterus sonography as a method for screening of endometrial cancer in postmenopausal women with or without diabetes mellitus for ten years period. 150 patients with diabetes mellitus and 150 patients from control group without diabetes mellitus were subjected to progesterone ampule 250 mg im. After bleeding occurred there were performed uterus sonographies before the abrasion probatoria, after the abrasion probatoria and on the 6th and 12th months. The performed abrasion probatoria showed full correspondence with exception of 3 cases. In 3 patients was found polipus endometrill, in one--atypical glandular hyperplasia, one case with carcinoma in situ and two cases with endometrial cancer. PMID- 7793521 TI - [The use of the Bethesda-terminology cytological system in clinical practice. A pilot study]. AB - The aim of the present study is to summarize the one-year experience in applying the Bethesda terminological system (BTS) for assessment of cervical cytology. The study was based on 164 women, aged from 18 to 45, of which 98 with early pregnancy and 66 not pregnant. The materials for cytological examination were prepared by classical techniques and then coloured with hemalaun-eosin. Cytological findings were interpreted according to the revised BTS (1991), and an assessment of the adequacy of smears, possible infectious and reactive changes was made. Intraepithelial lesions were classified in two categories--low and high grade lesions. The advantages and shortcomings of the proposed new terminological, cytological classification system for assessment of the uterine cervix are discussed. PMID- 7793523 TI - [Premature rupture of the amniotic sac with a term fetus and low pelvic score- its management]. AB - The author gives to us the results of the labour the rupture volamentorum ovi precocs to term--baby & low pelvic score about the period of 4 years (1987-1990). The analysis of results of two labours gives an opportunity to make the conclusions, which give a method of labour in clinic of Obstetrics & Gynaecology St. Zagora, giving a good results. PMID- 7793522 TI - [Contraception among adolescents]. AB - Adolescence is a period of which the contraception is difficult, because of lower compliance of the teenagers to this methods. The authors were observed the contraceptive uses in 792 pregnant adolescent girls, 264 of which with abortions (group A) and 528 teen-age mothers (group B). Only 12.88% of all patients have used birth control methods, usually with low and middle effects. We founded only 15 patients (1.89%) practiced hormonal contraception and 1 case (0.13%) with Intrauterine devise. The condoms for men was the most popular and useful in teenagers (4.23%), and Natural family planning methods were practiced from 52 (6.57%) patients. There was the statistically differences between adolescent girls included in group A and B about their contraceptive behaviors and live standards (p < 0.01). By the kind of contraceptive methods, there was a high differences in the teenagers with a hormonal uses (p < 0.05). PMID- 7793524 TI - [Myxoid myomas of the uterus]. AB - Two cases of myxoid smooth muscle tumours of the uterus have been reported. Clinical and morphological characteristics are briefly described. Inspite of the lack of cellular and nuclear atypia and mitotic figures below 2 in 10 high power fields, the clinical course was very malignant. A review of the literature on this new entity from the last 10-12 years has been made. PMID- 7793525 TI - [Puerperal involution of the uterus--its ultrasonic follow-up]. PMID- 7793526 TI - [Septic (endotoxic) shock in parturients--its management during labor and in the puerperium]. AB - Author provides a description of septic shock in a parturient. He analyses the clinical cause and proposes a therapeutic behaviour during labour and puerperium. PMID- 7793528 TI - [Myoma combined with a giant degenerating myomatous nodule]. PMID- 7793527 TI - [Neonatal infections caused by Streptococcus group B--their epidemiology, clinical picture, diagnosis, treatment and prevention]. PMID- 7793529 TI - [The diagnostic and surgical difficulties in abortion on demand in a woman with a bicornate uterus and an ovarian cyst]. PMID- 7793530 TI - [A clinical trial with the monophasic contraceptive Marvelon]. AB - The authors present their clinical experience with a monophasic preparation consisting of 30 mcg ethynyl estradiol and 150 mcg desogestrel (Marvelon, Organon). 121 cycles of 24 fertile women were followed. The results show a full contraceptive success, a stable cycle control as well as a low incidence of the side effects. PMID- 7793531 TI - [Transdermal estradiol--the possibility for replacement therapy in the postmenopause]. AB - The author presents his experience in the treatment of 21 early postmenopausal women (mean age of 49.2 yrs) with transdermal delivery of 17 beta-oestradiol (Estraderm TTS, Ciba). During the treatment Kuppermann index falls from 28.5 to 10.9. Karyopyknotic index increases from 6.8 to 23.4 and maturation index moves from 39:52:9 to 0:71:29. Genital bleeding occurs in 52% of the patients. The author concludes that the treatment with transdermal delivery of oestradiol could be used more widely for replacement therapy in the postmenopause. PMID- 7793532 TI - [Pregnancy and labor in young girls]. AB - The premature sexual contacts in adolescence are the most important factor for the high rate of teenage pregnancies. The authors were observed 528 pregnancies in adolescent girls (aged 13-17 years) and 100 mothers at their 20-24 years, as a control group. There were significant differences between the education level, ethnic origin and professional status in our populations. We founded in adolescent group anaemia in 13.64%, an overweight in 6.44% and preeclampsia eclampsia in 3.22%. The rate of premature delivery was higher (17.99%), caesarean section were performed in 5.44% and instrumental extraction was practiced in 1.70% of adolescent girls. Despite an pregnancy and delivery with a normal evolution, the mother-fetal prognoses were complicated from the hard psychoemotional, social and economical problems about these young mothers. PMID- 7793535 TI - Clinical studies with agents active on the 5-lipoxygenase pathway. AB - Leukotrienes may be considered asthmatic mediators. Compounds inhibiting their production and activity show promise in the treatment of asthma. Further clinical studies will determine the clinical usefulness of such agents. PMID- 7793536 TI - Future of anti-inflammatory therapy in asthma. PMID- 7793534 TI - The airway inflammatory response in allergic asthma and its relationship to clinical disease. AB - Endobronchial biopsy and lavage studies have revealed the presence of mast cell, eosinophil, T-lymphocyte and epithelial cell activation in asthma, along with the structural changes of tissue eosinophil infiltration, loss of superficial columnar ciliated epithelial cells and enhanced collagen deposition in the laminar reticularis. As these cellular and structural changes underlie the clinical features of asthma, i.e., symptom expression, variable airflow obstruction and bronchial hyperresponsiveness, and understanding of their induction and regulation is essential to the understanding of the asthmatic process. The acute airway response to allergen has been studied by the technique of local endobronchial allergen challenge with direct airway sampling in asthma. These studies identify allergen-mast cell interaction as the initial airway event, with mediator release inducing bronchoconstriction and enhancing vascular permeability. As preformed cytokines are present in mast cells, cytokine release from this cell population is likely to initiate the process of endothelial cell activation, with upregulation of cell adhesion molecules, and tissue cell recruitment. Subsequent cytokine elaboration from airway macrophages and T lymphocytes will perpetuate this response while in chronic clinical disease T lymphocytes, mast cells, matrix tissue, epithelial cells and eosinophils themselves are all likely to contribute to the cytokine pool within the airways and thus to the regulation of inflammatory cell migration and activation. PMID- 7793533 TI - [Prolonged pregnancy and trace elements: iron]. AB - Iron is an essential trace element and it is well known that the iron requirement steadily increase during pregnancy. The aim of this investigation was to compare the serum iron levels in normal and serotine pregnancy. Twenty-six women with serotine pregnancy (19 in 42 and 7 in 43 gestation week (g.w.)) were included in the study. The control group is consisted from 74 women with normal pregnancy. The serum iron concentration is elevated in the women with serotine pregnancy (24.59 +/- 11.60 mmol/(l), but the difference was not significant. The group with serotine pregnancy in 42 g.w. has even lower serum iron concentration than the women with normal pregnancy (19.44 +/- 6.52 mmol(l). The serum iron concentration was significantly elevated (p < 0.001) in serotine pregnancy in 43 g.w. compared with normal pregnancy as well as with serotine pregnancy in 43 g.w. The possible pathogenetic mechanisms of the observed changes are discussed. PMID- 7793537 TI - The role of indoor allergens in asthma. PMID- 7793538 TI - Recognition of the anaesthetist. PMID- 7793540 TI - Cardiovascular and catecholamine response to surgery in brain-dead organ donors. AB - Eleven brain-dead organ donors were studied during surgery. Plasma levels of adrenaline and noradrenaline were measured before and after skin incision, upon sternotomy and 15, 30 and 45 min thereafter. Haemodynamic changes were measured continuously throughout the observation period. Blood pressure and heart rate increased after skin incision, remained high at sternotomy then decreased towards the end of the observation period in six of the 11 patients. Plasma catecholamines increased promptly with the onset of surgical stimuli. We conclude that surgical stress can evoke an excessive rise of plasma adrenaline and noradrenaline and thus could impair allograft function. PMID- 7793539 TI - A prospective study to assess the demand for a high dependency unit. AB - We performed a prospective study in our teaching hospital to determine the demand for a High Dependency Unit where none had existed before. An admission criteria protocol was designed for medical and surgical patients and this was used in an intense surveillance of 22 acute wards over 2 weeks. It was predicted that a high dependency unit of eight beds would operate to capacity 50% of the time. An analysis of this type over a short period of time using similar admission criteria could be used to assist in the prediction of the necessary size of a High Dependency Unit facility in any hospital. PMID- 7793541 TI - Time course of action and intubating conditions following vecuronium, rocuronium and mivacurium. AB - The purpose of this study was to compare the time course of action and tracheal intubating conditions of vecuronium, rocuronium and mivacurium in anaesthetised patients. Anaesthesia consisted of thiopentone, fentanyl, N2O/O2 and isoflurane. After a 2 x ED90 dose the first attempt at tracheal intubation was made at 90 s. If required, maintenance doses of 0.5 x ED90 were administered. The intubating conditions after rocuronium were significantly better than those after vecuronium and mivacurium. The average onset times of rocuronium (172 s) and vecuronium (192 s) were significantly shorter than that of mivacurium (229 s). The clinical duration and recovery time were significantly shorter after mivacurium (13 and 6 min, respectively) than with vecuronium (33 and 14 min, respectively) and rocuronium (28 and 11 min, respectively). We conclude that rocuronium might be of advantage whenever the interval between the administration of the muscle relaxant and tracheal intubation must be short, whereas mivacurium may be of benefit if fast spontaneous recovery is required. PMID- 7793542 TI - The influence of nitrous oxide on propofol dosage and recovery after total intravenous anaesthesia for day-case surgery. AB - We studied the influence of nitrous oxide on the maintenance dose of propofol and recovery characteristics in 42 patients, aged 18-62 years, ASA 1 or 2, scheduled for day case inguinal herniotomy. Using a double-blind, randomised design, patients received anaesthesia with propofol-alfentanil-vecuronium-oxygen and either nitrous oxide or room air (FIO2 = 0.30). The rate of propofol infusion was adjusted depending on anaesthetic depth as judged using standard clinical criteria; alfentanil was administered on a weight basis. Patients' lungs were manually ventilated after tracheal intubation and muscle relaxation was reversed at the end of surgery with neostigmine and atropine. A series of psychomotor tests was performed pre-operatively and 30 and 120 min postoperatively. The mean maintenance doses of propofol were 0.084 mg.kg-1.min-1 in the N2O group and 0.088 mg.kg-1.min-1 in the air group (p = 0.97). In the nitrous oxide group the mean (SD) interval to spontaneous eye opening was 13.1 (7.3) min compared to 8.1 (4.9) min in the air group (p = 0.01). Similarly, the interval until obtaining a standardised response was 13.5 (5.3) min and 9.8 min (5.4) in the nitrous oxide and air groups, respectively (p = 0.04). The addition of nitrous oxide to propofol-alfentanil-vecuronium anaesthesia does not reduce propofol requirements and prolongs early recovery compared to air. PMID- 7793543 TI - Local anaesthesia for cannulation. Has practice changed? AB - A questionnaire study was undertaken to assess the influence of recently published, simple and conclusive research on the practice of anaesthetists in four centres. The research had clearly demonstrated the benefit of subcutaneous infiltration of local anaesthetic in reducing the pain of intravenous cannulation. Of the 81% who responded, 71% were aware of the research; 43% of these anaesthetists had altered their clinical practice as a result of the research and 73% used local anaesthesia for cannulae of 18 gauge or less, compared with only 46% of those who were unaware of the research. Practice comparisons were made between centres and grades of anaesthetist. Senior house officers were significantly less likely to be aware of the research than other grades. Anomalies were identified between the apparent awareness of the research and routine practice agreeing with the study findings. The value of research and the incorporation of clinical findings into everyday practice is discussed. PMID- 7793544 TI - Prevention of nausea and vomiting after day case gynaecological laparoscopy. A comparison of ondansetron, droperidol, metoclopramide and placebo. AB - We have compared the efficacy of ondansetron, metoclopramide, droperidol and placebo in the prevention of postoperative nausea and vomiting in 118 day stay patients undergoing laparoscopic gynaecological procedures. All received a standardised general anaesthetic of fentanyl, propofol, nitrous oxide in oxygen and isoflurane. Three to five min before induction of anaesthesia, patients were allocated to receive ondansetron 4 mg, metoclopramide 10 mg, droperidol 1 mg or placebo in a randomised, double-blind manner. Visual analogue scores for nausea, the incidence of emetic episodes, and analgesic and antiemetic consumption were recorded for 48 h postoperatively. The scores for nausea were significantly lower in the ondansetron group (p < 0.01) compared with the other three groups at 1, 2 and 4 h after operation; thereafter there was no difference. The incidence of emesis was lower (p = 0.063) and time to first oral fluids was shorter (p < 0.05) in the ondansetron group. Oral analgesic requirements were significantly greater in the ondansetron group over the 48 h study period. Two patients, one each in the placebo and metoclopramide groups, had to remain in hospital overnight because of persistent emetic symptoms. PMID- 7793545 TI - Comparison of central venous pressure measurements in the intrathoracic and the intra-abdominal vena cava in critically ill children. AB - A prospective study was conducted to compare simultaneous intrathoracic and intra abdominal central venous pressures in 10 critically ill, ventilated paediatric intensive care patients. Central venous pressures were measured using the water column technique over a 6 h study period. There was excellent correlation between intrathoracic and intra-abdominal vena caval pressure measurements (r = 0.974, p < 0.001). The difference between paired measurements did not exceed the limits of agreement (+/- 2SD, -2.36 to 4.42 cm H2O). The mean (SD) difference between readings was small (1.03 +/- 1.69 cmH2O) and was within clinically tolerable limits. These data suggest a clinically useful, close relationship between intra abdominal and conventional intrathoracic central venous pressure measurement in this group of patients. PMID- 7793546 TI - Somatosensory evoked potential changes following electro-acupuncture therapy in chronic pain patients. AB - Somatosensory evoked potentials were recorded in 20 healthy volunteers and 20 patients with chronic pain undergoing electro-acupuncture therapy. The values of absolute peak latency and amplitudes of N19 and P22 in the control group were compared with the corresponding baseline values in the study group and after electro-acupuncture therapy at three stages during a 10-treatment cycle. On these occasions the intensity of pain was recorded using a 100 mm visual analogue scale score. Each patient in the study group had 10 treatments given on alternate days. The absolute peak latency of N19 was significantly delayed (p < 0.05) in chronic pain patients when compared to the control group. This increase in latency of N19 persisted after the first electro-acupuncture treatment (p < 0.05), tended to revert to normal after the fifth treatment (p > 0.05) and reverted completely to control values after the 10th treatment (p > 0.05). Visual analogue scores also decreased significantly (p < 0.05) after the fifth and 10th electro-acupuncture sessions. These observations suggest that there is an interaction of the neural mechanisms of electro-acupuncture with the thalamic generator of somatosensory evoked potentials i.e. N19. PMID- 7793547 TI - Epidural infusion of alfentanil or diamorphine with bupivacaine in labour--a dose finding study. AB - Following induction of epidural analgesia with 0.375% bupivacaine, 120 healthy parturients were randomly assigned in a double blind fashion to one of eight infusion groups. All received 8 ml.h-1 of 0.125% bupivacaine either alone (control group), or with alfentanil at 133, 266 or 400 micrograms.h-1 (groups A1 A3) or with diamorphine at 133, 266, 400 or 533 micrograms.h-1 (groups D1-D4). Significantly longer top-up intervals were achieved with the two highest doses of both alfentanil and diamorphine when compared with bupivacaine alone (p < 0.01), making the minimum effective doses 266 micrograms.h-1 of alfentanil and 400 micrograms.h-1 of diamorphine. Perineal analgesia was better in all the opioid groups compared with the control group (p < 0.05). The intensity of motor block was greater in the control group (p < 0.05). The incidence of pruritus did not differ between groups. The highest dose of diamorphine caused significantly more nausea. No significant neonatal side-effects were demonstrated. PMID- 7793548 TI - Epidural infusions of bupivacaine and diamorphine in labour. AB - Three different concentrations of bupivacaine, 0.125%, 0.062% and 0.031%, all with diamorphine 0.0025%, were given as an epidural infusion at 10 ml.h-1 to 63 mothers in labour. When the three infusions were compared, significant differences were found in maternal requirements for top-ups and the degree of motor block, but there were no differences in the pain scores. The reduced motor block was not associated with a reduction in the instrumental delivery rate. PMID- 7793550 TI - Measurement of tidal flow using a transit-time ultrasonic breath analyser. AB - The ability of the Transit-time Ultrasonic Breath Analyser (TUBA, GHG Medical Electronics GMBH, Zurich, Switzerland) to measure peak flow and tidal volume in the laboratory was tested using a variety of flow and pressure conditions, chosen to simulate the respiratory patterns of patients receiving mechanical ventilatory support. A stable zero baseline was achieved by acoustic damping of the TUBA flow sensor head. A piston pump was used to generate sinusoidal flow pattern, with a peak flow range from 0.1 to 1.51.s-1. The calculated peak flow matched the peak flow measured by the TUBA. The TUBA accurately measured tidal volumes (+/- 10%) delivered using three different flow patterns over a range of volumes from 0.25 to 11. We conclude, that once modified, the TUBA can provide an accurate measurement of peak flow and tidal volume over a range of values likely to be encountered during mechanical ventilation of the lungs. PMID- 7793549 TI - Evaluation of the influence of movement on saturation readings from pulse oximeters. AB - This study aimed to develop a protocol for assessing the influence of movement on oxyhaemoglobin saturation readings from pulse oximeters. Thirty-six volunteers took part in the study. In each volunteer, each hand was monitored by both a Nellcor N200 oximeter using a disposable probe and by a Datex Satlite DS103 oximeter using a clip-on finger probe. Volunteers made five standardised movements during which output was recorded from all four oximeters. All movements were associated with apparent decreases in oxyhaemoglobin saturation which were statistically significant for two movements with the Nellcor equipment and for four movements with the Datex equipment. Movement was associated with increases in the magnitude of pulse amplitude, but this was not quantitatively associated with magnitude of artefactual changes in saturation. Use of this standardised movement protocol allows quantification of movement artefact from pulse oximeters and should facilitate the development of equipment less affected by movement. PMID- 7793552 TI - Anaesthetic and postoperative recovery rooms. Some notes on their early history. AB - From time to time questions are asked about the origins and history of anaesthetic and postoperative recovery rooms. Early accounts of the use of these facilities, and their introduction into hospital planning, are reviewed. PMID- 7793551 TI - The output of an 'empty' Tec 3 vaporizer. AB - The output of 30 Tec 3 vaporizers (halothane, enflurane and isoflurane) was studied, starting at the point where no liquid was visible in the content window. At 6 l.min-1 and 1% v/v initial output, consistent delivery was on average maintained for in excess of 90 (range 55-120) min. Thereafter, output declined rapidly. At the flows and concentrations studied there is a significant reserve in the vaporizing chamber, but it is likely that when higher flows and concentrations are used this reserve may be substantially reduced. PMID- 7793553 TI - Deaths associated with anaesthesia. A report on 1,000 cases. 1956. PMID- 7793554 TI - An asthmatic weaned from a ventilator using a laryngeal mask. AB - A case is described in which a patient was unable to be weaned from ventilatory support whilst the trachea remained intubated. She was successfully weaned using a laryngeal mask. PMID- 7793555 TI - Physostigmine in recovery from anaesthesia. AB - Intravenous ketamine anaesthesia has been used by the British army in the field for many years. A recognised problem has been the unpredictable recovery profile this produces. We anaesthetised 28 ASA 1 patients using a standard British military technique. At termination of the anaesthetic, half of the patients were given a physostigmine/glycopyrronium mixture and half were given the equivalent volume of saline 0.9%. There was a significant difference between the two groups with regard to recovery times (p < 0.001). There was no significant difference with regard to other variables. In trauma anaesthesia the improved recovery profile from the use of physostigmine following ketamine anaesthesia may lead to earlier evacuation of the patient. PMID- 7793556 TI - Prolonged starvation in paediatric surgery. AB - An evaluation of the pre-operative preparation of 285 children attending Sheffield Children's Hospital for elective surgery showed that prolonged and unnecessary starvation takes place, particularly in children over 1 year of age who have their operation in the morning. Excessive starvation of children is unkind and unnecessary. In order to prevent it a revision of current starvation guidelines is required. PMID- 7793557 TI - Analgesia following day-case knee arthroscopy--the effect of piroxicam with or without bupivacaine infiltration. AB - Sixty patients presenting for day-case arthroscopy of the knee under general anaesthesia were studied. Patients were randomly allocated to receive, in addition to intramuscular piroxicam 20 mg, either bupivacaine 0.25% 20 ml applied locally to the knee at the end of the procedure (n = 30) or no further intra operative analgesia (n = 30). Visual analogue pain scores were significantly lower at 1, 2 and 4 h postoperatively in the bupivacaine group (p < 0.05). A higher proportion of patients in the piroxicam-only group required supplemental analgesia before discharge from hospital. The combination of piroxicam and bupivacaine provided superior analgesia to piroxicam alone. PMID- 7793558 TI - Facilitation of laryngeal mask insertion. Effects of lignocaine given intravenously before induction with propofol. AB - The effects of pretreatment with lignocaine administered intravenously on the insertion of the laryngeal mask airway were investigated in 80 unpremedicated, ASA 1 or 2, adult day-case patients in a randomised, double-blind, placebo controlled trial. Patients received either intravenous lignocaine 1.5 mg.kg-1 or an equivalent volume of sodium chloride 0.9%. Induction of anaesthesia was achieved with propofol given via a syringe driver at a fixed rate of 600 ml.h-1 until the patient dropped a weighted syringe. No opioid or sedative drugs were given prior to induction. Pain on injection of propofol was recorded. Jaw opening, ease of insertion of the laryngeal mask, coughing, gagging and airway patency were all scored on three-point scales immediately after mask insertion re attempted. This cycle was continued until success was achieved and the number of such cycles recorded. There were no differences between the lignocaine and control groups with respect to induction dose of propofol, degree of jaw opening, or amount of gagging. Laryngeal mask insertion was facilitated by pretreatment with lignocaine administered intravenously, without an alteration in induction dose of propofol (p < 0.05). Coughing and airway obstruction were both significantly reduced by pretreatment with lignocaine, as was the incidence of failure of insertion requiring deepening of anaesthesia (p < 0.05). PMID- 7793559 TI - Postoperative shivering. PMID- 7793560 TI - Difficulty in inserting a laryngeal mask airway. PMID- 7793561 TI - An unusual complication of percutaneous tracheostomy. PMID- 7793562 TI - Pretracheal abscess following retrograde tracheal intubation. PMID- 7793563 TI - Fentanyl versus morphine for patient-controlled analgesia. PMID- 7793564 TI - An unusual complication of intra-osseous infusion during paediatric resuscitation. PMID- 7793566 TI - Early venous catheter blockade: a cause for immediate concern. PMID- 7793565 TI - Visceral vapours. PMID- 7793567 TI - Is smoking good for you? PMID- 7793568 TI - Continuous spinal anaesthesia and cauda equina syndrome. PMID- 7793569 TI - Pain during injection of rocuronium bromide. PMID- 7793570 TI - The place of 0.375% bupivacaine in obstetric anaesthesia. PMID- 7793571 TI - Another subdural block, or was it? PMID- 7793572 TI - Nebulised adrenaline in adults with upper airway obstruction. PMID- 7793573 TI - Insertion of the Montgomery T-tube. PMID- 7793575 TI - Caution in the use of disposable tubing. PMID- 7793574 TI - Age-related haematological disturbances. PMID- 7793576 TI - Evaluation of the SMART needle. PMID- 7793577 TI - A defective connector. PMID- 7793579 TI - Single medial injection pf peribulbar anaesthesia. PMID- 7793578 TI - A hazardous modification of a heat and moisture exchanger. PMID- 7793580 TI - Murray's chloroform mask. PMID- 7793582 TI - Anaesthesia for laser pharyngoplasty--a comparison of the tracheal tube with the reinforced laryngeal mask airway. AB - A common cause of snoring is palatal flutter which occurs when turbulent air flow causes the flexible soft palate to flutter. Surgical correction involves either removal of the soft palate or a reduction in its flexibility. Laser pharyngoplasty is a new surgical procedure designed to stiffen the soft palate. It presents a unique combination of problems for the anaesthetist. In this paper we describe the evolution of the anaesthetic technique for laser pharyngoplasty and analyse the results of the first 165 cases. Points of particular interest include the use of the reinforced laryngeal mask airway compared with the tracheal tube and late onset pain. PMID- 7793581 TI - Inguinal field block for adult inguinal hernia repair using a short-bevel needle. Description and clinical experience in Solomon Islands and an Australian teaching hospital. AB - One of the limitations of an inguinal field block is that it does not reliably produce complete anaesthesia. The purpose of this study was to describe a modified short-bevel needle technique, facilitating correct needle placement, for inguinal hernia repair. Anaesthetists from two different institutions performed the described infiltration blocks. Prospective data were collected from these groups, each having 30 patients. We evaluated the safety and reliability of the described block. Of the 60 patients, two were "failed" blocks, requiring conversion to general anaesthesia. There were no other major intraoperative or recovery room complications. Results of the modified inguinal field block showed a 97% ability to achieve a "fair" block or better. Intraoperative and postoperative data showed high surgeon and patient satisfaction for the block. The described block using a short-bevel needle is recommended as a suitable method for adult patients undergoing inguinal hernia repair. PMID- 7793583 TI - Modulating effects of lignocaine on propofol. AB - Pain is a well known complication of propofol injection. Premixing with lignocaine 0.1 mg.kg-1 and injection into a large forearm vein has been recommended. The amount of lignocaine to be added is often empirical when the vein on the dorsum of the hand is used. In this study we attempt to determine the optimal amount of lignocaine necessary to reduce pain when propofol is injected into a hand vein. Our study shows that a propofol emulsion containing 0.05% lignocaine is effective in reducing the incidence of propofol injection pain. The addition of lignocaine also reduces the incidence of excitatory effects. Increasing the dosage of lignocaine above 0.05% does not improve the results. PMID- 7793584 TI - Ketorolac or pethidine for analgesia after elective laparoscopic sterilization. AB - Laparoscopic sterilization is commonly performed as a day surgery procedure despite difficulties in providing adequate postoperative analgesia for all patients. We have examined the analgesic utility of intramuscular ketorolac in this setting by comparing it with intramuscular pethidine, both given after induction in a randomized, double-blind study in sixty such patients. Although the analgesic effects of the two drugs were comparable in the immediate postoperative period, ketorolac provided significantly better analgesia four hours after surgery (pain score of 2.7 v. 4.2, P = 0.006). The recovery times taken to awake, to ambulate and for discharge were all significantly shorter after ketorolac (4.6 v. 8.8 min, P = 0.01; 178 v. 260 min, P = 0.0005; 242 v. 320 min, P = 0.02), and the unplanned admission rate was also significantly less after ketorolac (7% v. 33%, P = 0.01). Ketorolac appears to be a useful supplement for analgesia after laparoscopic sterilization, providing improved analgesia as well as decreased recovery time and fewer unplanned admissions. PMID- 7793585 TI - Comparison of halothane, enflurane and isoflurane kidney effects through alanine aminopeptidase/urine creatinine values. AB - The kidney effects of halothane, enflurane and isoflurane were evaluated by using the ratio of urinary excretion of alanine aminopeptidase (AAP) to urine creatinine. Thirty patients in ASA class 1 or 2 were studied. None had renal disease nor received nephrotoxic drugs. Groups 1, 2 and 3 received halothane, enflurane and isoflurane respectively. Creatinine and AAP activities in urine spot tests, serum creatinine and BUN levels were determined preoperatively and on the first and second postoperative days. Urine AAP activity and AAP/urine creatinine values increased significantly on the first and second postoperative days compared with the preoperative values in all groups (P < 0.05). The present study did not reveal any significant difference in the kidney effects of halothane, enflurane and isoflurane through AAP/creatinine in spot urine values. PMID- 7793586 TI - Rationalizing venepuncture pain: comparison of lignocaine injection, Butterfly (21 gauge and 23 gauge) and Venflon (20 gauge). AB - Two hundred and seventy-eight patients scheduled for all types of surgery and premedicated with diazepam and metoclopramide were randomly allocated to one of four groups to compare the relative pain of an injection of 0.25 ml of lignocaine 1% via a 25 gauge needle with the pain of the siting of a 21 gauge Butterfly (Abbott), 23 gauge Butterfly or a 20 gauge Venflon (Vigo Spectramed). The injection of lignocaine and insertion of the 23 gauge Butterfly were associated with the least complaints of pain and least observed responses to pain. The 21 gauge Butterfly and 20 gauge Venflon were associated with complaints of greater pain and more pain responses. We conclude that a pre-cannulation injection of lignocaine causes minimal discomfort and is the most appropriate means of reducing the discomfort of venous cannulation when not using skin penetrating analgesic creams. PMID- 7793587 TI - Is there a role for selective decontamination of the digestive tract in primarily infected patients in the ICU? AB - The role of selective decontamination of the digestive tract (SDD) for the prevention of nosocomial infection in critically ill patients remains controversial, and the efficacy of this technique in patients who are already infected on presentation to the intensive care unit has not previously been assessed. We performed a double-blind randomized placebo controlled trial of SDD (parenteral cefotaxime, six-hourly oral and enteral polymyxin E, tobramycin, and amphotericin B vs placebo) for all infected patients presenting to the ICU requiring mechanical ventilation for more than 48 hours and ICU stay of more than 5 days. Daily clinical and microbiological monitoring for secondary infection was undertaken until hospital discharge. In all, 59 selective decontamination and 76 placebo fully comparable patients fulfilled criteria for enrollment and analysis (APACHE II 15.2 vs 15.1). The number of patients receiving SDD who developed nosocomial infections was significantly reduced (P = 0.048), and there were no infections caused by the enterobacteriaceae or Candida spp in this group. No difference in ICU (17.5 vs 18.8 days) or hospital stay (32.7 vs 34.2 days) or mortality (17% vs 22.3%) was shown. Critically ill, primarily infected patients are protected from nosocomial infection by the use of SDD. PMID- 7793589 TI - Correction of splanchnic oxygen deficit in the intensive care unit: dopexamine and colloid versus placebo. AB - Correction of the splanchnic oxygen deficit indicated by low gastric intramucosal pH (pHi < 7.35) appears to reduce ICU mortality. Dopexamine hydrochloride is in clinical use for this purpose but its efficacy has not been fully investigated. We report the results of a prospective, randomized, placebo-controlled study with a crossover design to assess the efficacy of dopexamine in correcting low pHi. Twelve patients in whom pHi < 7.32 was detected during eight-hourly monitoring were randomized to receive either incremental dopexamine (4-6 micrograms/kg/min) with colloid or 5% dextrose for three hours prior to crossover. There was no difference in pHi between treatments despite cardiovascular effects during dopexamine infusion. There was, however, a time-related increase in pHi suggesting a beneficial effect of conventional therapy. Dopexamine hydrochloride at 4-6 micrograms/kg/min in conjunction with colloid is not a clinically useful therapy to correct the splanchnic oxygen deficit indicated by low pHi. PMID- 7793588 TI - Bronchoscopic insufflation of room air for the treatment of lobar atelectasis in mechanically ventilated patients. AB - Segmental and lobar pulmonary atelectasis is a common occurrence in mechanically ventilated patients. Standard therapy for atelectasis relies on positive pressure ventilation, positive and expiratory pressure (PEEP), tracheobronchial toilet and regular chest physiotherapy. Various adjuncts to physiotherapy such as bronchoscopic clearance of secretions have not proved to be of additional benefit. Bronchoscopic clearance of secretions followed by insufflation of room air at 30 cm H2O into the atelectatic segment was employed on ten occasions in mechanically ventilated patients. Rapid re-expansion of the collapsed segment or lobe occurred in seven out of the ten treatments. PMID- 7793591 TI - Problems in the modelling of inert gas kinetics. AB - The models used to describe the kinetics of inert gases during underwater diving are inadequate. Medical practitioners and scientists interested in such diving have attempted to quantitatively describe the behaviour of nitrogen in compressed air diving since 1908, with little success. The problems encountered during this diving research are relevant to anaesthesia theory and practice. PMID- 7793590 TI - The Medical Emergency Team. AB - The concept of a Medical Emergency Team was developed in order to rapidly identify and manage seriously ill patients at risk of cardiopulmonary arrest and other high-risk conditions. The aim of this study was to describe the utilization and outcome of Medical Emergency Team interventions over a one-year period at a teaching hospital in South Western Sydney. Data was collected prospectively using a standardized form. Cardiopulmonary resuscitation occurred in 148/522 (28%) calls. Alerting the team using the specific condition criteria occurred in 253/522 (48%) calls and on physiological/pathological abnormality criteria in 121/522 (23%) calls. Survival rate to hospital discharge following cardiopulmonary arrest was low (29%), compared with other medical emergencies (76%). PMID- 7793592 TI - Parental presence at induction of anaesthesia: a survey of N.S.W. hospitals and tertiary paediatric hospitals in Australia. AB - We undertook a survey of N.S.W. hospitals and tertiary paediatric hospitals in other States to determine their practice in relation to parental presence at induction of anaesthesia of children. There were 135 responses to 174 questionnaires. Twenty-one indicated that no children were anaesthetized at their institution and one was inadequately filled out. One hundred and thirteen questionnaires were assessed. Only 44% of departments had an official policy on parental attendance. A quarter of all hospitals described their facilities as entirely suitable, and a half compromised to allow parents to be present. The remaining quarter described their facilities as unsuitable. Overall, two-thirds of hospitals never or only sometimes had parents present at induction, and this applied equally to day stay patients and inpatients. Tertiary hospitals were more likely to have parents present, however they were more likely to have suitable facilities. The most common reason cited for parental attendance was parental expectation of being present, closely followed by the individual anaesthetist's philosophy. The most common reason for parents not attending was the individual anaesthetist's philosophy, followed by inadequate staffing. PMID- 7793593 TI - Postoperative vomiting in children. AB - A survey of the incidence of postoperative vomiting in 1476 children was conducted over a two-month period as part of our quality assurance programme. The incidence of vomiting was 24%, and was highest in children over three years of age and in those receiving opioids. The incidence is lower than that recorded in an earlier (1981) survey in our hospital. Changes in anaesthetic practices may have contributed to this decrease. PMID- 7793594 TI - Continuous intravascular blood gas analysis during aortic aneurysm repair: the Paratrend 7. PMID- 7793595 TI - Measurement of neuromuscular blockade--a comparison between a new "homemade" force displacement transducer and the accelerometer. AB - Train-of-four (TOF) ratios are compared between a new homemade force pressure transducer and a commercially available accelerometer. Twenty adult patients were studied and 600 simultaneous TOF ratio pairs were recorded during anaesthesia with varying degrees of muscle relaxation. Laboratory testing revealed that the output from the homemade device was linear up to 900 g and that there was a linear relationship between the output from the new device and the accelerometer (y = 0.802x + 5.167, R = 0.943, t = 69, P < 0.0001). Although the homemade device underestimates the accelerometer TOF ratio by 20%, it is a reliable and economic alternative to commercially available products for measuring TOF ratios. PMID- 7793596 TI - Traumatic tracheal disruption--diagnostic difficulties. PMID- 7793597 TI - Diagnosis of cryptantigen exposure and polyagglutinability: management of transfusion therapy in a patient with sepsis and colitis. PMID- 7793598 TI - Cardiovascular collapse after combined spinal anaesthesia and interscalene brachial plexus block. PMID- 7793599 TI - Anaesthesia for caesarean section in a patient with acute fatty liver of pregnancy. PMID- 7793600 TI - Brainstem anaesthesia following a peribulbar block for eye surgery. PMID- 7793601 TI - Myocardial dysfunction in a 23-month child with acute poststreptococcal glomerulonephritis. PMID- 7793602 TI - Fatal hepatic necrosis following cardiac surgery and enflurane anaesthesia. PMID- 7793603 TI - Midazolam and parenteral nutrition in the management of life-threatening hyperemesis gravidarum in a diabetic patient. PMID- 7793607 TI - Bilateral vocal cord paralysis. PMID- 7793605 TI - Fatal foetal outcome from diabetic ketoacidosis in pregnancy. PMID- 7793604 TI - Envenomation by Ingram's Brown snake (Pseudonaja ingrami). PMID- 7793606 TI - Anaesthesia in a patient with agoraphobia. PMID- 7793608 TI - Clinical indicators: what does a stay in the recovery room for longer than two hours indicate? PMID- 7793609 TI - Cancer of the trachea, an unusual presentation. PMID- 7793610 TI - Fibreoptic guided intubation: setting up a teaching programme. PMID- 7793611 TI - Anaesthesia mortality. PMID- 7793612 TI - A non-muscle-relaxant technique for video-assisted thoracoscopic thymectomy in myasthenia gravis. PMID- 7793614 TI - Anaesthetic alerts. PMID- 7793613 TI - Anaesthesia for stenting tracheal stenosis. PMID- 7793615 TI - Pacemaker inhibition by calf stimulator. PMID- 7793616 TI - The Sprotte spinal needle: spot the introducer! PMID- 7793617 TI - Blind nasal intubation is not performed blindly. PMID- 7793618 TI - Separation and size determination of circular and linear single-stranded DNAs by alkaline agarose gel electrophoresis. AB - The electrophoretic mobility of single-stranded DNA (ssDNA) through agarose gels depends on size (number of bases; molecular weight), topology (linear or circular), and conformation (secondary and tertiary folding through base pairing and stacking), as well as on gel concentration and field strength. Under alkaline conditions that disrupt secondary and tertiary structures, the linear and circular forms of a given single-stranded DNA can be easily resolved. The mobility ratios, mulinear/mucircular, depend strongly on gel concentration and less strongly on DNA size. Protocols have been developed to determine conveniently the size within 2% and the fractions of circular and linear forms for ssDNA sizes on the order of 10 kb. PMID- 7793619 TI - Assay of pancreatic lipase with the surface acoustic wave sensor system. AB - A new type of surface acoustic wave sensor system for assaying the activity of pancreatic lipase has been proposed. The assay of this enzyme is based on the change in conductance of the solution caused by the release of a fatty acid, using triolein as a substrate. A linear relationship between frequency response and enzyme concentration is obtained. Kinetic parameters of pancreatic lipase, i.e., the Michaelis constant for triolein and the corresponding maximum initial rate, are estimated to be 5.46 mM and 7551.6 Hz/min, respectively. The effects of temperature and pH value are also investigated. PMID- 7793620 TI - Optimization of calcium phosphate transfection for bovine chromaffin cells: relationship to calcium phosphate precipitate formation. AB - Optimal conditions for formation of calcium phosphate-DNA precipitates and for chromaffin cell transfection by the calcium phosphate method were examined. A relationship was observed between turbidity of calcium phosphate solutions and the ability of calcium phosphate-DNA mixtures to give efficient transfection of bovine chromaffin cells. Under optimal conditions up to 35% of chromaffin cells in cultures transfected with plasmid DNA encoding human proenkephalin or Escherichia coli beta-galactosidase expressed the respective proteins. Important factors for transfection were the pH (6.95) and buffer employed for calcium phosphate-DNA precipitate formation, the amount and type of DNA, and the absence of serum in the cultures. Additionally, phosphate and calcium concentrations in the culture medium during incubation of cells with DNA are critical. Optimal conditions for transfection of chromaffin cells were also useful for transfection of clonal BSC-40 cells, an African green monkey kidney cell line. These results suggest that the optimal conditions described here for chromaffin cells may have broad applicability to other cell types. In addition, the results suggest that it is possible to optimize the solutions used for transfection conditions by monitoring calcium phosphate formation. PMID- 7793621 TI - A continuous spectrophotometric assay for 5-aminolevulinate synthase that utilizes substrate cycling. AB - A continuous spectrophotometric assay for determining 5-aminolevulinic acid synthase activity is described. The assay is based upon coupling the production of coenzyme A by 5-aminolevulinic acid synthase to the reduction of NAD+ by alpha ketoglutarate dehydrogenase and monitoring the increase in absorbance at 340 nm. Reduction of NAD+ is stoichoimetric with formation of 5-aminolevulinic acid. Kinetic parameters for glycine and succinyl-CoA are similar to those reported for other assays which measure the formation of 5-aminolevulinic acid. Regeneration of succinyl-CoA in the alpha-ketoglutarate dehydrogenase reaction facilitates determination of initial rates at subsaturating concentrations of this substrate. This assay will permit the rapid accumulation of kinetic data and aid in mechanistic analyses of both 5-aminolevulinic acid synthase and its recombinant mutants. PMID- 7793622 TI - A spectrophotometric assay for the determination of the catalytic efficiency of plasminogen activators using a slowly hydrolyzed plasmin substrate. AB - A simple spectrophotometric assay for the determination of the catalytic efficiency and activity of plasminogen activators is presented. The assay system contains activator, plasminogen, and the chromogenic substrate N-benzoyl-L arginine-p-nitroanilide (BAPA). Plasmin production is monitored continuously by the hydrolysis of BAPA under non-steady-state, first-order conditions with respect to plasminogen. Apparent catalytic efficiency constants are calculated from the values obtained for the apparent first-order rate constant of activation. The results obtained with the present method were compared with the catalytic efficiency determined through the measurement of kcat and Km, using a different system, under steady-state conditions. Tissue plasminogen activator in the absence and presence of fibrinogen and high-molecular-weight urokinase were used as model activators. Potential applications are discussed. PMID- 7793624 TI - A general method for detecting and sizing large plasmids. AB - We have devised a method for detecting and estimating the sizes of large bacterial plasmids in the presence of genomic DNA by pulsed-field gel electrophoresis (PFGE). Bacteria harboring plasmids were embedded in agarose and lysed using a rapid protocol. Plugs were incubated with S1 nuclease and subjected to PFGE in agarose gels. S1 nuclease converted supercoiled plasmids into full length linear molecules. Large plasmids migrated as discrete bands that were readily observed after ethidium staining. Their sizes were reliably estimated by comparison with linear DNA markers. Without S1 digestion, supercoiled plasmids migrated at rates that were not a simple function of their molecular weights, making size determinations problematic. S1-PFGE detected megaplasmids up to 609 kilobases (kb) in six genera of bacteria (Agrobacterium, Escherichia, Klebsiella, Pseudomonas, Salmonella, and Staphylococcus). The procedure gave size values consistent with previous estimates for characterized megaplasmids. Eight new plasmids between 102 and 316 kb were discovered in Klebsiella and Staphylococcus. S1-PFGE avoids the difficulties of plasmid isolation, eliminates the preparation of probes, and does not require knowledge of restriction enzyme cleavage sites. It detects multiple large plasmids up to the limits of PFGE and can be used to screen for megaplasmids in many strains simultaneously. PMID- 7793623 TI - Utilization of patterns of biotinyl-polypeptides as a promising analytical target for bacterial identification. AB - The family of biotin enzymes, which are involved in carboxylation, transcarboxylation, and decarboxylation reactions in cells, is essential and conserved for bacteria. The prosthetic group biotin is stably linked to the biotinyl-polypeptide by an amide bond. Since avidin interacts with biotin in an irreversible manner, the patterns of biotinyl-polypeptides for bacterial cells could be revealed by probing them with an avidin-enzyme complex in Western blots of total cellular proteins. In this way, the family of commonly existing gene products of bacteria could be monitored and compared without the use of specific DNA probes, oligonucleotide primers, or antibodies. In this study, this approach was tested and it was found that different species of bacteria showed different patterns of biotinyl-polypeptides. Our results indicate that patterns of biotinyl polypeptides can be a promising analytical target for bacterial identification. PMID- 7793625 TI - Analysis of leukotrienes, lipoxins, and monooxygenated metabolites of arachidonic acid by reversed-phase high-pressure liquid chromatography. AB - Arachidonic acid can be converted to a large number of metabolites by various lipoxygenases, cyclooxygenase, and other enzymes. Because of the complex profiles of products formed by many types of cells, high-pressure liquid chromatography (HPLC) has proved to be an invaluable technique for their purification and analysis. In the present study we have developed improved methods for the analysis of complex mixtures of eicosanoids by HPLC using binary gradients containing trifluoroacetic acid (TFA), which allows considerable manipulation of the retention times of the cysteine-containing leukotrienes (LTs) LTC4, LTD4, and LTE4 relative to those of other eicosanoids. With a gradient between 0.003 and 0.005% TFA and a 4.6-mm-i.d. column of Spherisorb ODS-2, cysteinyl-LTs are very well resolved from one another and are separated as a group with retention times longer than those of all other major eicosanoids. These conditions can be used for the analysis of prostaglandin B2 (PGB2), LTB4, monohydroxyeicosatetraenoic acids (HETEs), and cysteinyl-LTs in only 30 min. Slightly longer analysis times must be used for the separation of more polar eicosanoids such as hydroxy metabolites of LTB4 and lipoxins. We have also developed methods for the analysis of eicosanoids using a midbore (3.2 mm i.d.) column containing Spherisorb ODS-2, which improves sensitivity and reduces solvent consumption. In this case higher concentrations (0.04 to 0.05%) of TFA have been used, resulting in retention times for cysteinyl-LTs between those of the cyclooxygenase product 12-hydroxy 5,8,10-heptadecatrienoic acid and the HETEs. This approach permits analysis of PGB2, LTB4, HETEs, and cysteinyl-LTs in only 20 min. Samples which also contain hydroxy-LTB4 and lipoxins can be analyzed in 40 min. The above techniques are highly reproducible and give baselines which are free of interfering peaks. PMID- 7793627 TI - Atomic absorption spectrometric determination of cadmium and lead in human and artificial teeth by direct atomization technique. AB - A method of graphite furnace atomic absorption spectrometry (GFAAS) with a direct atomization technique has been developed for the determination of trace amounts of Cd and Pb in human teeth and artificial teeth. The samples were ground to a particle size of less than 10 microns and mixed with the same amount of graphite powder. One-half to 2 mg of mixed sample was weighed in a tared graphite cup and atomized in a cup-type graphite furnace according to the heating program that was established. Absorbances were determined by integration of the spectral lines in the absorbance vs time spectrum. Calibration was affected using aqueous standard solutions. The results for six human tooth samples and two artificial tooth samples were in good agreement with the values obtained by GFAAS for dissolved samples. The relative standard deviations were 3.1-12% (n = 10) for Cd (19-95 ng g-3) and 0.9-8.1% (n = 10) for Pb (1.43-6.32 micrograms g-3). The determination limits corresponding to twice the standard deviation (sigma, n = 10) for blank measurements were 13 pg for Cd and 53 pg for Pb. PMID- 7793626 TI - Extractive derivatization of the 12-lipoxygenase products, hepoxilins, and related compounds into fluorescent anthryl esters for their complete high performance liquid chromatography profiling in biological systems. AB - Facile methods for the detection of intact hepoxilins, monohydroxy-epoxide derivatives of arachidonic acid formed through the 12-lipoxygenase pathway, are unavailable because (i) an absence in these compounds of an appropriate chromophore for sensitive detection by uv exists, (ii) these compounds are sensitive to the acidic workup leading to varying degrees of decomposition, and (iii) they decompose to the derivatization procedures required for their analysis by gas chromatography mass spectrometry. Herein we apply a method which introduces a fluorescent ester chromophore to the carboxylic group of the hepoxilins under conditions which do not require acidification leading to stabilization of the derivative which is extracted into an organic solvent in situ. This procedure quantitatively derivatizes hepoxilins in a biological sample, permitting the detection of hepoxilins after a TLC purification with a limit of 50 pg/sample. This method permits the profiling of 12-HETE, hepoxilins A3 and B3, as well as the corresponding epoxide hydrolase products, trioxilins A3 and B3, in a biological sample by reverse-phase HPLC with fluorescent detection. We also report on the fluorescent and mass spectral properties of these derivatives using a liquid chromatography mass spectrometry LCMS interface with thermospray ionization. PMID- 7793628 TI - Protein farnesyltransferase: measurement of enzymatic activity in 96-well format using TopCount microplate scintillation counting technology. AB - Protein farnesyltransferase (PFT) catalyzes the transfer of the farnesyl group of farnesyl pyrophosphate (FPP) to proteins ending with a carboxy-terminal CAAX motif, forming a thioether linkage to the cysteine residue of the protein. A method is described herein for measurement of PFT activity in 96-well format using TopCount microplate scintillation counting technology. This method has the advantages of requiring only a single transfer from reaction vessels or wells of a 96-well reaction plate to the filtration wells of a 96-well Packard UniFilter GF/B filtration plate following acid precipitation and of allowing liquid scintillation counting to be conducted directly in the filtration plate without the need for either removal of the filter from the plate or transfer of the filter to liquid scintillation vials prior to radioactivity assessment. Using rat brain cytosol as the source of PFT, H-ras as the source of farnesyl acceptor protein, and [1-3H]FPP as the farnesyl donor, the incorporation of radiolabeled farnesyl residues into H-ras was found to be a linear function of both the time of incubation at 37 degrees C (up to 75 min) and the concentration of rat brain cytosolic protein present during incubation (up to 40 micrograms protein), and to be dependent on the concentration of H-ras (Km = 1.1 microM) and FPP (Km = 0.6 microM) present in the incubation reaction. In the presence of 4 microM H-ras, 0.5 microM FPP, 4 mM MgCl2, and 20 microM ZnCl2, the specific activity of rat brain cytosolic PFT measured using this methodology was 0.253 +/- 0.036 (SD; n = 30) pmol H-ras farnesylated per minute of incubation at 37 degrees C per milligram cytosolic protein. The signal-to-noise ratio for H-ras farnesylation using this methodology averaged 25 relative to incubation in the absence of H-ras (background farnesylation of cytosolic proteins) and 50 relative to incubation in the absence of both H-ras and rat brain cytosol (background filter associated radioactivity). Intraassay variability averaged 4% and interassay variability averaged 9%. FPP mimetics from a variety of distinct structural classes, previously shown to act as competitive inhibitors of the FPP-utilizing enzyme, squalene synthetase (SQS), also inhibited PFT activity measured using this methodology, but exhibited approximately 300- to 500-fold specificity for inhibition of SQS relative to inhibition of PFT, when both enzymes were measured at their respective Km FPP concentrations, suggesting structural differences between the FPP binding sites of the two enzymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7793630 TI - Enzymatic synthesis of ATP analogs and their purification by reverse-phase high performance liquid chromatography. AB - The enzymatic syntheses of ATP analogs, such as tubercidin 5'-triphosphate, formycin A 5'-triphosphate, and etheno-ATP, from their respective mono- and diphosphate are described. The reaction products were purified by reverse-phase HPLC using a C-18 matrix and a volatile mobile phase at pH 7, with tributylamine as the ion-pairing agent. Each of the analogs required a buffer of somewhat different composition for the baseline separation of reaction product and reactants. The elutions were isocratic and allowed several successive runs without any intermediate equilibration of the column. After freeze-drying of the pooled fractions, the yield of the synthesized nucleoside triphosphate was approximately 70%. The described procedures are applicable either for analytical investigations or for semi-preparative purposes. PMID- 7793631 TI - Development of the on-line high-performance liquid chromatography/thermospray mass spectrometry method for the analysis of phospholipid molecular species in rat brain. AB - An on-line thermospray liquid chromatography/mass spectrometry method was developed to rapidly analyze phosphoglyceride molecular species in biological fluid. After total lipid extraction, the extract was subjected to the analysis using on-line reversed-phase high-performance liquid chromatography (HPLC) and filament-on thermospray mass spectrometry. Using nonconventional HPLC conditions, partial separation of individual phospholipid class (phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine) and partial separation of molecular species within each class were achieved. In addition, good peak shape was maintained throughout the analysis. By monitoring characteristic fragment ions (diacylglycerol ions) formed in the filament-on thermospray process and according to the retention time, individual molecular species in each phospholipid class can be identified. Using this method, we observed significant differences in the molecular species composition of each phospholipid class in rat whole-brain lipid. Although nonlinear calibration curves were observed for all the diacylglycerol ions monitored, even in the presence of internal standard, semiquantitative and quantitative results still could be obtained for a mixture of phospholipids. PMID- 7793629 TI - The functional effects of biotinylation of anti-angiotensin-converting enzyme monoclonal antibody in terms of targeting in vivo. AB - The effect of modification with biotin N-hydroxysuccinimide ester of mouse monoclonal antibody to angiotensin-converting enzyme, anti-ACE Mab 9B9, on its targeting to endothelial cells has been studied in vitro and in vivo. By in vitro assay, Mab 9B9 biotinylated at a biotin/IgG molar ratio in reaction mixture (B/IgG ratio) of 0.7-2.2 bound streptavidin monovalently and retained antigen binding capacity. Mab 9B9 biotinylated at a B/IgG ratio of 20 and higher bound streptavidin polyvalently. Extensive biotinylation (B/IgG ratio of 60 and higher) led to dramatic reduction of Mab 9B9 Ag-binding capacity and to reduction of Mab 9B9 recognition by goat polyclonal antibody to mouse IgG. Radiolabeled Mab 9B9 biotinylated at a B/IgG ratio of 6 (b6-Mab 9B9) bound effectively to cultured vascular endothelium, with affinity characteristics similar to nonbiotinylated Mab 9B9. Endothelial cells internalized both Mab 9B9 and b6-Mab 9B9 to the same extent (60% internalization at 3 h incubation at 37 degrees C). Degradation of cell surface-associated Mab 9B9 or b6-Mab 9B9 was very low (< 1% as measured by TCA solubility of radiolabel). In contrast, degradation of internalized b6-Mab 9B9 was more profound than that of Mab 9B9 (20 +/- 3% vs 6 +/- 1%, P < 0.01). After injection in rats, radiolabeled b6-Mab 9B9 had a biodistribution pattern similar to that of radiolabeled Mab 9B9. Both preparations effectively accumulated in the lung (15-20% of injected dose/g of tissue vs 2% of injected dose/g of blood).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793632 TI - Luminescent visualization of low amounts of cytochrome P450 and hemoproteins by luminol in acrylamide gels. AB - In this paper we apply luminol (5-amino-2,3-dihydro-1,4-phthalazinedione), a light-emitting substrate, in conjunction with H2O2 to the luminescence labeling of hemoproteins. We describe in detail a photodetection device which permits an efficient recording of the light emitted by heme-containing proteins resolved in acrylamide gels. The sensitivity of this procedure, when compared to the classical 3,3'-5,5'-tetramethylbenzidine staining method, results in a 5- to 20 fold enhancement with standard hemoproteins (lactoperoxidase, catalase, cytochrome P450 2B4, horseradish peroxidase, hemoglobin, myoglobin, and cytochrome b5). The potential applications of this technique are illustrated by the detection of cytochrome P450 in microsomes from plant as well as from animal extrahepatic tissues which possess low amounts of this cytochrome. PMID- 7793633 TI - Analysis of 8-hydroxy-2'-deoxyguanosine in rat urine and liver DNA by stable isotope dilution gas chromatography/mass spectrometry. AB - A previously developed gas chromatographic/mass spectrometric method was applied to the measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat liver DNA and in rat urine. For DNA samples, the method included: (i) fortification of samples with [15N]DNA (internal standard), (ii) enzymatic hydrolysis of DNA to deoxynucleosides, (iii) degradation of native nucleosides by treatment with trifluoroacetic acid and hydrazine, (iv) purification by C18 solid-phase extraction (SPE), (v) derivatization (acetylation followed by pentafluorobenzylation, Ac-PFB), and (vi) GC/MS analysis of the derivatives. For urine, the following methodology was used: (i) fortification of the samples with 8-18OHdG, (ii) prepurification by C18/OH SPE, (iii) derivatization, (iv) high performance liquid chromatography purification of the Ac-PFB derivatives, and (v) GC/MS analysis. The precision of the method was demonstrated by carrying out replicate analysis of several urine and DNA samples: within-run and between-run variability was less than 5 and 8%, respectively. The analytical approaches were sufficiently sensitive to quantitate the urinary excretion of 8-OHdG (490 +/- 70 pmol/kg/24 h; sample size, 600 microliters urine) and to measure the level of 8 OHdG in liver DNA (20 8-OHdG/10(6) deoxynucleosides; sample size, 30 micrograms DNA) of rats not deliberately exposed to oxidative stress. Major advantages over previous methods are increased precision due to the use of proper isotopically labeled internal standards, and increased sensitivity due to the optimization of cleanup procedures. The simultaneous analysis of standards of three different oxidized nucleosides, namely 8-OHdG, thymidine glycol, and 5-hydroxy-methyl-2' deoxyuridine, is shown. PMID- 7793634 TI - A long-lived batch reaction system of cell-free protein synthesis. AB - Several reaction conditions of cell-free protein synthesis such as temperatures, buffers, tRNAs, and creatine phosphate were intensively investigated and optimized to prolong protein synthesis and make it more efficiently in a batch system. As a result of these modifications, the protein synthesis reaction continued for 10 h so that about 30 micrograms of dihydrofolate reductase (DHFR) protein derived from Escherichia coli was synthesized in 1 ml of reaction mixture. In this improved system, translational reactions of other mRNAs such as rabbit beta-globin, Xenopus beta-globin, and tobacco mosaic virus RNA also continued for about 10 h. In addition, protein synthesis directed by uncapped dhfr mRNA containing a viral cap-independent translation initiation-mediating sequence continued for 10 h, resulting in the synthesis of 18 micrograms of DHFR protein per milliliter of reaction mixture. PMID- 7793635 TI - Solid-phase hybridization capture of low-abundance target DNA sequences: application to the polymerase chain reaction detection of Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum. AB - Polymerase chain reaction (PCR) has been widely applied to the detection of microorganisms. Overall sensitivity of PCR tests may be substantially reduced due to a large excess of nontarget DNA and inhibitory substances in the sample. We used a 5'-biotinylated 513-bp probe from the 3' region of the IS 900 element specific for Mycobacterium paratuberculosis (Mptb) to capture target Mptb DNA from crude sample DNA extracts. Captured target DNA was separated using streptavidin-coated magnetic particles (Dynal). Since the IS 900 element shares homology over this region with IS 902 in Mycobacterium avium subsp. silvaticum (Mavs), target DNA from this other pathogen was also retained. Highly specific PCR for the detection of either organism directed to the 5' regions of IS 900 or IS 902 was then performed directly on the solid phase. Hybridization capture of target DNA using sequence adjacent to the desired specific PCR site applied to Mptb increased overall sensitivity of detection in tissue and fecal extracts 10- to 100-fold. False positives due to contamination artifact were substantially excluded since the capture probe did not retain amplicons from the detection PCR. Development of the method to involve covalent 5' immobilization of capture probes on heat-resistant polymers should, in the future, provide a simple system with broad potential applications. PMID- 7793636 TI - Phospholipid/alkanethiol bilayers for cell-surface receptor studies by surface plasmon resonance. AB - Supported hybrid bilayer membranes (HBM) composed of a monolayer of phospholipid and a monolayer of alkanethiol associated with a thin gold film on glass are useful as model lipid bilayer membranes for studying membrane receptor-ligand and cell-cell binding events by surface plasmon resonance (SPR). Measurements of specific binding of proteins and lipid vesicles to well-defined HBMs have been performed under conditions of continuous flow using a commercial SPR instrument (BIAcore). HBMs are shown to be stable in flow and to block nonspecific adsorption of proteins to the alkanethiol/gold surface. The use of such supported lipid bilayers in flow provides a means of conducting equilibrium and kinetic studies of models of ligand-cell and cell-cell interactions with receptors or ligands in a membrane environment. Compared to the extended dextran polymer layer that is currently used for surface modification of BIAcore "sensor chips," the described HBMs provide a well-defined surface that will permit less ambiguous modeling of these important biological interactions. PMID- 7793637 TI - A colorimetric assay for measuring activation of Gs- and Gq-coupled signaling pathways. AB - Current assays for functional activation of Gs-coupled receptors usually involve quantitation of adenylyl cyclase or measurement of cAMP concentration by radioimmunoassay. The activation of Gq-coupled receptors is commonly assayed by measurement of the production of inositol triphosphate or diacylglycerol from phosphatidylinositol 4,5-bisphosphate or of changes in intracellular calcium. These assays generally require large numbers of cells (10(5)-10(6)) and/or the use of radioactive materials. We have developed a rapid nonradioactive colorimetric assay that utilizes a beta-galactosidase (lacZ) gene fused to five copies of the cyclic AMP response element (CRE) to detect the activation of CRE binding protein that results from an increase in intracellular cAMP or calcium. This assay can be performed using as few as 30,000 cells in a 96-well format with the end products measured simultaneously in a microplate reader. Consequently, a single individual can readily assay 1000 samples a day. Using this assay, the fold increase in beta-galactosidase activity was similar in magnitude to increases in cAMP or adenylyl cyclase activity and was approximately linear from 0.01 to 0.27 fmol/cell of intracellular cAMP. Furthermore, pharmacological characterization of one of the melanocortin receptors, mMC5-R, using this assay resulted in a similar order of potency for several melanocortin peptides to that obtained with a commonly used adenylyl cyclase enzyme assay. This assay is also useful for the characterization of Gq-coupled receptors as is demonstrated here using cells transfected with the mouse bombesin receptor. The large-scale capacity of this assay makes it an excellent method for screening molecules of interest acting on Gs- and Gq-coupled receptors. PMID- 7793638 TI - Facile, in situ matrix-assisted laser desorption ionization-mass spectrometry analysis and assignment of disulfide pairings in heteropeptide molecules. AB - During a routine analysis of disulfide-linked synthetic heterodipeptides by matrix-assisted laser desorption ionization (MALDI) mass spectrometry with linear detection we observed not only the expected mass of the dipeptide, but also the mass of the individual constituent monomer peptides. This was surprising because the peptide was purified as an intact dipeptide and no overt attempt was made to reduce the disulfide linkage before mass analysis. In contrast, analysis of the same sample by electrospray ionization mass spectrometry gave the mass of the dipeptide only. To investigate this further, two additional model heterodipeptides were prepared and all three were used to systematically study several matrix-assisted laser desorption ionization mass spectrometry parameters. These parameters were three different matrices (alpha-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid, and sinapinic acid), both positive and negative modes of detection, and varying the acceleration voltage from 5 to 20 kV. Except for the sinapinic acid matrix where poor-quality spectra were obtained, all three model heterodipeptides fragmented under the tested conditions in a manner consistent with the cleavage of disulfide bonds, although the absolute level was sample dependent. The precise mechanism of disulfide cleavage during analysis is unknown, but the cleavage we observed appears to originate during the initial ionization event. Because the MALDI process involves irradiating samples with a laser, the fragmentation of disulfide-linked peptides that we observe bears some resemblance to light-induced homolytic cleavage of aqueous solutions of the amino acid cystine, although other mechanisms for fragmentation are also possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793640 TI - Improved method for silver staining of glycoproteins in thin sodium dodecyl sulfate polyacrylamide gels. AB - A method for detection of glycoproteins in thin sodium dodecyl sulfate polyacrylamide gels was developed by a combination of (i) initial periodic acid oxidation/Alcian blue staining and (ii) subsequent staining with silver nitrate. The procedure allowed detection of as little as 1.6 ng of alpha 1-acid glycoprotein and 8-40 ng of a polydisperse mucin sample, which is at least 10 times more sensitive than previously published methods. The method should be very useful for assessment of sample purity and detection of glycoproteins in dilute mixed samples. PMID- 7793639 TI - Efficient analysis of cytochrome P4501A catalytic activity, porphyrins, and total proteins in chicken embryo hepatocyte cultures with a fluorescence plate reader. AB - An efficient method for measuring polychlorinated biphenyl-mediated induction of cytochrome P4501A, using the ethoxyresorufin-O-deethylase (EROD) assay, and total porphyrins in chicken embryo hepatocyte cultures is described. Hepatocytes were cultured in 48-well plates, assays were carried out within the wells, and concentrations of the product of the EROD reaction (resorufin), porphyrins, and total proteins were measured in the same wells with a fluorescence plate reader. The method differs from previous methods developed in this laboratory in that three fluorophors were measured in the same well rather than two. PMID- 7793641 TI - Ferrireductase activity in Saccharomyces cerevisiae and other fungi: colorimetric assays on agar plates. PMID- 7793642 TI - Microassay of adenylosuccinase by capillary electrophoresis. PMID- 7793643 TI - Concentration of dilute protein for gel electrophoresis. PMID- 7793644 TI - Aerosolized prostacyclin. In search of the ideal pulmonary vasodilator. PMID- 7793646 TI - Pharmacokinetic model selection for target controlled infusions of propofol. Assessment of three parameter sets. AB - BACKGROUND: Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. METHODS: Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data. RESULTS: Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time. CONCLUSIONS: Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference. PMID- 7793645 TI - Inferences about respiratory muscle use after cardiac surgery from compartmental volume and pressure measurements. AB - BACKGROUND: After upper abdominal surgery, patients have been observed to have alterations in respiratory movements of the rib cage and abdomen and respiratory shifts in pleural and abdominal pressure that suggest dysfunction of the diaphragm. The validity of making such deductions about diaphragm function from these observations is open to discussion. METHODS: In eight adult patients, American Society of Anesthesiologists physical status 2, scheduled for elective cardiac surgery, we measured respiratory rate, tidal volume, rib cage and abdominal cross-section changes, and esophageal (Pes) and gastric (Pga) pressures preoperatively, 1 day postoperatively, and 5 days postoperatively. These data were analyzed in detail by following the variables through each respiratory cycle. RESULTS: Mean delta Pga/delta Pes decreased from 0.73 preoperatively to 0.56 1 day postoperatively and recovered to 0.47 5 days postoperatively. Plots of Pes against Pga and rib cage against abdominal expansion (Konno-Mead diagrams) were constructed. Six patients showed a postoperative pattern of breathing similar to that seen in patients who have undergone abdominal surgery: a decrease in the ratio of delta Pga/delta Pes and a shift toward rib cage expansion, with an increase in breathing rate and a decrease in tidal volume. This change was accomplished in most cases by the use of abdominal muscles in expiration with an increase in inspiratory intercostal muscle action without an increase in diaphragm activation, that is, a shift in the normal balance of respiratory muscle use in favor of muscles other than the diaphragm. A different ventilatory pattern was observed in the other two patients, consisting of minimal rib cage excursion and a large abdominal excursion. In these cases tidal volume was generated largely by contraction and relaxation of abdominal muscles with probable reduction in diaphragm activity. In addition, five patients exhibited positive changes in Pes at the end of inspiration that corresponded to closure of the upper airway, relaxation of inspiratory muscles, and subsequent opening of the airway with sudden exhalation, producing a grunt. CONCLUSIONS: Indirect measurements of respiratory muscle action based on pressure and chest wall motion are easier than are assessments based on implanted electromyogram electrodes and sonomicrometers that measure electric activity and muscle length, respectively, directly. Interpretation requires numerous assumptions and detailed analysis of phase relations among the variables. In patients after thoracic surgery, however, these measurements strongly point to a shift in the distribution of motor output toward muscles other than the diaphragm. PMID- 7793647 TI - Clinical effects and maternal and fetal plasma concentrations of epidural ropivacaine versus bupivacaine for cesarean section. AB - BACKGROUND: Ropivacaine is a new amide local anesthetic structurally similar to bupivacaine and mepivacaine. Previous studies showed that ropivacaine has a similar clinical effect as bupivacaine with regard to sensory anesthesia and slightly less motor blockade than bupivacaine. Ropivacaine appears to be less cardiotoxic and arrhythmogenic than bupivacaine. The clinical and pharmacokinetic effects of 0.5% ropivacaine (5 mg/ml) versus 0.5% bupivacaine (5 mg/ml) when used epidurally for elective cesarean section were investigated. METHODS: Using a randomized, double-blind study design, 60 ASA physical status 1 or 2 term parturients presenting for elective cesarean section received either 0.5% bupivacaine (150 mg) or 0.5% ropivacaine (150 mg) epidurally in appropriate fractionated doses over a 10-min period. Onset, duration, and regression of sensory and motor blockade were noted until complete resolution was observed. Quality of intraoperative anesthesia and abdominal wall muscle relaxation were noted. Maternal plasma concentrations of local anesthetic were determined before anesthetic administration and 5, 10, 20, 30, and 60 min and 2, 3, 6, 8, 12, and 24 h after drug injection in 20 subjects. Umbilical cord blood was obtained at time of delivery for acid-base values and determination of the free and total plasma concentration of local anesthetic. Neonates also were examined for neurobehavioral assessments by Scanlon's and Neurologic and Adaptive Capacity Scores at 2 and 24 h after delivery. RESULTS: All patients received satisfactory anesthesia for operation. The onset, duration, and regression of sensory blockade were similar for both groups. Onset of degree 1 and 2 motor blockade was faster, and duration of degree 1 motor block was longer in the group receiving bupivacaine. Hemodynamic sequelae were similar between groups. All neonates had 5 min Apgar scores of 7 or greater and normal acid-base values and neurobehavioral assessments. Pharmacokinetic analysis showed that the Cmax was similar for both drugs (1.3 +/- 0.09 for ropivacaine and 1.1 +/- 0.09 micrograms/ml for bupivacaine). The T1/2 of the terminal decline in plasma concentration was shorter for ropivacaine versus bupivacaine (5.2 +/- 0.60 versus 10.9 +/- 1.08 h, respectively; P < 0.01). The free (i.e., unbound) concentrations of ropivacaine were approximately twice those of bupivacaine in both maternal and neonatal blood at the time of delivery. The ratio of umbilical vein to maternal vein concentration of unbound drug was 0.72 for ropivacaine and 0.69 for bupivacaine. CONCLUSIONS: Ropivacaine, 0.5%, epidurally provided satisfactory and similar sensory anesthesia compared to 0.5% bupivacaine for elective cesarean section. The Cmax was similar for both drugs, although the terminal half-life of ropivacaine was significantly shorter, and the blood concentrations of free ropivacaine were significantly greater than that for bupivacaine. These values were less than concentrations shown to be toxic in animals. PMID- 7793648 TI - Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers. AB - BACKGROUND: Premedication with oral clonidine may improve the quality and duration of lidocaine spinal anesthesia, but this effect has not been examined in a quantitative fashion. METHODS: Eight volunteers received 50 mg lidocaine (1.5% dextrose free) both with and without 0.2 mg oral clonidine 1.5 h before spinal anesthesia in a randomized, double-blind, placebo-controlled, crossover fashion. Sensory block was assessed by pinprick, transcutaneous electric stimulation equivalent to surgical incision, and duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed by isometric force dynamometry. Episodes of bradycardia, hypotension, and sedation were recorded. RESULTS: Regression of pinprick was unchanged with clonidine. However, duration of tolerance to electric stimulation was increased at the knee (28 +/- 24 min) and ankle (31 +/- 28 min) with clonidine (P < 0.05). The duration of tolerance to tourniquet-induced pain was increased with clonidine (14 +/- 12 min; P < 0.05). The duration of motor block was increased at the quadriceps (20 +/- 13 min) and gastrocnemius (33 +/- 24 min) muscle groups with clonidine (P < 0.05). Although clonidine decreased systolic blood pressure (13 +/ 4 mmHg, P < 0.003) and heart rate (13 +/- 5 beats/min; P = 0.02), no subjects had hypotension or bradycardia. The incidence of sedation was greater with clonidine than with plain lidocaine (50% vs. 0%, P < 0.04). DISCUSSION: Premedication with oral clonidine prolonged sensory and motor block from lidocaine spinal anesthesia. The exact mechanism whereby oral clonidine prolongs spinal anesthesia remains to be determined. PMID- 7793649 TI - Postpartum changes in the minimum alveolar concentration of isoflurane. AB - BACKGROUND: Minimum alveolar concentration (MAC) is decreased in pregnancy, but it is not known how quickly after delivery MAC returns to normal. We measured the MAC of isoflurane in a group of women undergoing elective tubal ligation after delivery. METHODS: After delivery, 20 patients underwent inhalational induction of anesthesia with isoflurane and tracheal intubation. MAC was determined in each patient by observing the response to a 10-s, 50-Hz, 80-mA transcutaneous tetanic electric stimulus to the ulnar nerve at various concentrations of isoflurane. The end-tidal concentration of isoflurane was kept constant for at least 10 min before each stimulus, and the concentration of isoflurane was ultimately varied in steps of 0.05 vol% until we obtained a sequence of three alternate responses: move-not move-move or not move-move-not move. The MAC for each subject was taken as the mean of the two concentrations just permitting and just preventing movement. A venous blood sample was taken immediately before induction of anesthesia for measurement of progesterone concentration. MAC was compared with time after delivery and plasma progesterone concentrations by Kendall's rank correlation. RESULTS: There was a positive correlation between MAC and the time after delivery (P < 0.001). The median MAC of isoflurane was 0.775 vol% (range 0.675-0.775 vol%) in five women 24-36 h postpartum. MAC was more variable, 0.825 vol% (0.675-0.975 vol%) in nine women 36-72 h postpartum, whereas six patients more than 72 h postpartum had a MAC of 1.125 vol% (1.025-1.175 vol%). The correlation between MAC and plasma progesterone concentration was almost statistically significant (P = 0.060). CONCLUSIONS: The MAC of isoflurane was reduced in women 24-36 h postpartum and gradually increased to normal values by 72 h postpartum. PMID- 7793650 TI - The minimum alveolar concentration of isoflurane in patients undergoing bilateral tubal ligation in the postpartum period. AB - BACKGROUND: The minimum alveolar concentration (MAC) of volatile anesthetics is decreased during pregnancy, but MAC in the early postpartum period has not been reported. The aim of this study was to determine the MAC of isoflurane and to evaluate the relation between MAC and serum progesterone and beta-endorphin in patients after delivery. METHODS: Eight patients undergoing elective bilateral tubal ligation during general anesthesia in the early postpartum period (< 12 h postpartum) and eight patients undergoing this procedure in the late postpartum period (12-25 h postpartum) were studied. Eight patients undergoing bilateral tubal ligation more than 6 weeks after delivery served as control subjects. Anesthesia was induced with propofol and maintained with isoflurane in oxygen to a steady end-tidal concentration of 0.8-1.0 vol% for 10 min. Reaction to a standardized electric stimulation applied to the forearm was graded as positive (gross or delayed movement) or negative. By using the bracketing technique, the concentration of isoflurane was increased or decreased by 0.1 vol%, depending on the positive or negative responses. RESULTS: The MAC (mean +/- SD) in patients in the early postpartum period was significantly less (0.75 +/- 0.17 vol%) than that in control subjects (1.04 +/- 0.12 vol%; P < 0.01) and that in patients in the late postpartum period (0.95 +/- 0.2 vol%; P < 0.05). The difference in MAC values between late postpartum and control was not significant (P > 0.05). There was an inverse correlation between progesterone concentration postpartum and time after delivery (r = -0.527; P = 0.036), but P = 0.744). There was no correlation between plasma progesterone or beta-endorphin and MAC by multiple regression (r = 0.166; P = 0.950). CONCLUSIONS: Isoflurane MAC remains 28% less than normal within the 1st 12 h postpartum and then returns to normal 12-25 h after delivery. PMID- 7793653 TI - Methohexital impairs osmoregulation. Studies in conscious and anesthetized volume expanded dogs. AB - BACKGROUND: Anesthetic agents influence central regulations. This study investigated the effects of methohexital anesthesia on renal and hormonal responses to acute sodium and water loading in dogs in the absence of surgical stress. METHODS: Fourteen experiments (two in each dog) were performed in seven well-trained, chronically tracheotomized beagle dogs kept in highly standardized environmental and dietary conditions (2.5 mmol sodium and 91 ml water/kg body weight daily). Experiments lasted 3 h, while the dogs were conscious (7 experiments) or, after 1 h control, while they were anesthetized (7 experiments) with methohexital (initial dose 6.6 mg/kg body weight and maintenance infusion 0.34 mg.min-1.kg-1 body weight) over a period of 2 h. In both experiments, extracellular volume expansion was performed by intravenous infusion of a balanced isoosmolar electrolyte solution (0.5 ml.min-1.kg-1 body weight). Normal arterial blood gases were maintained by controlled mechanical ventilation. In another five dogs the same protocol was used, and vasopressin (0.05 mU.min-1.kg-1 body weight) was infused intravenously during methohexital anesthesia. RESULTS: Values are given as means. During methohexital anesthesia, mean arterial pressure decreased from 108 to 101 mmHg, and heart rate increased from 95 to 146 beats/min. Renal sodium excretion decreased; urine volume increased; and urine osmolarity decreased from 233 to 155 mosm/l, whereas plasma osmolarity increased from 301 to 312 mosm/l because of an increase in plasma sodium concentration from 148 to 154 mmol/l. Plasma renin activity, plasma aldosterone concentration, plasma atrial natriuretic peptide, and plasma antidiuretic hormone concentrations (range 1.8-2.8 pg/ml) did not change in either protocol. In the presence of exogenous vasopressin (antidiuretic hormone 3.3 pg/ml), water diuresis did not occur, and neither plasma osmolarity nor the plasma concentration of sodium changed. CONCLUSIONS: Methohexital may impair osmoregulation by inhibiting adequate pituitary antidiuretic hormone release in response to an osmotic challenge. PMID- 7793651 TI - Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics. AB - BACKGROUND: Sevoflurane has low blood and tissue solubility and is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Although sevoflurane uptake and distribution and fluoride formation have been described, the pharmacokinetics of HFIP formation and elimination are incompletely understood. This investigation comprehensively characterized the simultaneous disposition of sevoflurane, fluoride, and HFIP. METHODS: Ten patients within 30% of ideal body weight who provided institutional review board-approved informed consent received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction, after which anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Sevoflurane and unconjugated and total HFIP concentrations in blood were determined during anesthesia and for 8 h thereafter. Plasma and urine fluoride and total HFIP concentrations were measured during and through 96 h after anesthetic administration. Fluoride and HFIP were quantitated using an ion selective electrode and by gas chromatography, respectively. RESULTS: The total sevoflurane dose, calculated from the pulmonary uptake rate, was 88.8 +/- 9.1 mmol. Sevoflurane was rapidly metabolized to the primary metabolites fluoride and HFIP, which were eliminated in urine. HFIP circulated in blood primarily as a glucuronide conjugate, with unconjugated HFIP < or = 15% of total HFIP concentrations. In blood, peak unconjugated HFIP concentrations were less than 1% of peak sevoflurane concentrations. Apparent renal fluoride and HFIP clearances (mean +/- SE) were 51.8 +/- 4.5 and 52.6 +/- 6.1 ml/min, and apparent elimination half-lives were 21.4 +/- 2.8 and 20.1 +/- 2.6 h, respectively. Renal HFIP and net fluoride excretion were 4,300 +/- 540 and 3,300 +/- 540 mumol. Compared with the estimated sevoflurane uptake, 4.9 +/- 0.5% of the dose taken up was eliminated in the urine as HFIP. For fluoride, 3.7 +/- 0.4% of the sevoflurane dose taken up was eliminated in the urine, which, because a portion of fluoride is sequestered in bone, corresponded to approximately 5.6% of the sevoflurane dose metabolized to fluoride. CONCLUSIONS: Sevoflurane was rapidly metabolized to fluoride and HFIP, which was rapidly glucuronidated and eliminated in the urine. The overall extent of sevoflurane metabolism was approximately 5%. PMID- 7793652 TI - Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation. AB - BACKGROUND: Sevoflurane is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Cytochrome P450 2E1 is the major isoform responsible for sevoflurane metabolism by human liver microsomes in vitro. This investigation tested the hypothesis that P450 2E1 is predominantly responsible for sevoflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. METHODS: Twenty-one patients within 30% of ideal body weight, who provided institutional review board-approved informed consent and were randomized to receive disulfiram (500 mg oral, n = 11) or nothing (control, n = 10) the night before surgery, were evaluated. All patients received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction. Thereafter, sevoflurane was discontinued, and anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Blood sevoflurane concentrations during anesthesia and for 8 h thereafter were measured by gas chromatography. Plasma and urine fluoride and total (unconjugated plus glucuronidated) HFIP concentrations were measured by an ion-selective electrode and by gas chromatography, respectively, during anesthesia and for 96 h postoperatively. RESULTS: Patient groups were similar with respect to age, weight, sex, case duration, and intraoperative blood loss. The total sevoflurane dose, measured by cumulative end-tidal sevoflurane concentrations (3.7 +/- 0.1 MAC-h; mean +/- SE), total pulmonary uptake, and blood sevoflurane concentrations, was similar in both groups. In control patients, plasma fluoride and HFIP concentrations were increased compared to baseline values intraoperatively and postoperatively for the first 48 and 60 h, respectively. Disulfiram treatment significantly diminished this increase. Plasma fluoride concentrations increased from 2.1 +/- 0.3 microM (baseline) to 36.2 +/- 3.9 microM (peak) in control patients, but only from 1.7 +/- 0.2 to 17.0 +/- 1.6 microM in disulfiram-treated patients (P < 0.05 compared with control patients). Peak plasma HFIP concentrations were 39.8 +/- 2.6 and 14.4 +/- 1.1 microM in control and disulfiram-treated patients (P < 0.05), respectively. Areas under the plasma fluoride- and HFIP-time curves also were diminished significantly to 22% and 20% of control patients, respectively, by disulfiram treatment. Urinary excretion of fluoride and HFIP was similarly significantly diminished in disulfiram-treated patients. Cumulative 96-h fluoride and HFIP excretion in disulfiram-treated patient was 1,080 +/- 210 and 960 +/- 240 mumol, respectively, compared to 3,950 +/- 560 and 4,300 +/- 540 mumol in control patients (P < 0.05). CONCLUSIONS: Disulfiram, an effective P450 2E1 inhibitor, substantially decreased fluoride ion and HFIP production during and after sevoflurane anesthesia. These results suggest that P450 2E1 is a predominant P450 isoform responsible for human sevoflurane metabolism in vivo. PMID- 7793654 TI - Inhibition by volatile anesthetics of endogenous glutamate release from synaptosomes by a presynaptic mechanism. AB - BACKGROUND: Synaptic transmission is more sensitive than axonal conduction to the effects of general anesthetics. Previous studies of the synaptic effects of general anesthetics have focused on postsynaptic sites of action. We now provide direct biochemical evidence for a presynaptic effect of volatile anesthetics on neurotransmitter release. METHODS: Rat cerebrocortical synaptosomes (isolated presynaptic nerve terminals) were used to determine the effects of general anesthetics on the release of endogenous L-glutamate, the major fast excitatory neurotransmitter. Basal and evoked (by 4-aminopyridine, veratridine, increased KCl, or ionomycin) glutamate release were measured by continuous enzyme-coupled fluorometry. RESULTS: Clinical concentrations of volatile halogenated anesthetics, but not of pentobarbital, inhibited 4-aminopyridine-evoked Ca(2+) dependent glutamate release. Halothane also inhibited veratridine-evoked glutamate release but not basal, KCl-evoked, or ionomycin-evoked glutamate release. Halothane inhibited both the 4-aminopyridine-evoked and the KCl-evoked increase in free intrasynaptosomal [Ca2+]. CONCLUSIONS: Inhibition of glutamate release from presynaptic nerve terminals is a potential mechanism of volatile anesthetic action. Comparison of the sensitivity of glutamate release evoked by secretogogues that act at various steps in the neurotransmitter release process suggests that halothane does not affect Ca(2+)-secretion coupling or vesicle exocytosis but inhibits glutamate release at a step proximal to Ca2+ influx, perhaps by blocking presynaptic Na+ channels. Synaptosomal glutamate release evoked by 4-aminopyridine should provide a useful system for further characterization of the presynaptic effects of anesthetics. PMID- 7793655 TI - Regulation of norepinephrine release by beta 2-adrenergic receptors during halothane anesthesia. AB - BACKGROUND: Presynaptic receptors control norepinephrine (NE) release. It has been hypothesized that epinephrine stimulates prejunctional beta 2-adrenergic receptors to facilitate NE release from sympathetic nerve endings, and therefore, presynaptic receptors controlling NE release are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously demonstrated beta 2-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic activity in vivo by decreasing the NE spillover rate into plasma. The goal of the current study was to determine the effect of halothane on beta 2-adrenergic receptor augmented NE release in a canine hind-limb experimental model. METHODS: Seven female dogs were studied awake and during halothane anesthesia (1.0 minimum alveolar concentration). A trace dosage of [3H]NE (15 microCi over a 1-min period and 0.6 microCi/min thereafter) was infused into the femoral vein. Before and during femoral arterial administration of isoproterenol at two dosages (30 and 80 mg/min), hind-limb blood flow was measured by an ultrasonic flow probe and hind limb NE spillover by an isotope dilutional technique. RESULTS: In awake dogs, isoproterenol significantly increased hind-limb blood flow and NE spillover into the hind limb. Halothane had no effect on baseline or isoproterenol-stimulated hind-limb blood flow (a postjunctional beta 2 effect) but significantly inhibited the isoproterenol-induced increase in hind-limb NE spillover (a prejunctional beta 2 effect). CONCLUSIONS: The isoproterenol-mediated increase in NE release is inhibited by halothane anesthesia, indicating that halothane inhibits prejunctional beta 2-adrenergic receptor regulation of NE release. PMID- 7793656 TI - Ketamine has stereospecific effects in the isolated perfused guinea pig heart. AB - BACKGROUND: S(+)-Ketamine is judged to produce more potent anesthesia than either the racemate or the R(-) ketamine isomer because of differential activation of specific cerebral receptors. Other than central nervous system effects, the most important side effects of ketamine occur in the cardiovascular system. We examined the direct cardiac effects of the isomers and the racemate of ketamine in the isolated perfused guinea pig heart. METHODS: Twenty-three guinea pig hearts were perfused by the Langendorff technique with modified 37 degrees C Krebs-Ringer's solution (97% oxygen and 3% carbon dioxide) at a constant perfusion pressure. Eight animals were pretreated with reserpine to deplete hearts of catecholamines. These pretreated hearts were also perfused with Krebs Ringer's solution containing propranolol, phenoxybenzamine, and atropine to block any remaining effects of catecholamines and of acetylcholine. Five additional hearts were perfused with naloxone to block cardiac opioid receptors. Ten hearts were not treated. All 23 hearts were then exposed to four increasing equimolar concentrations of each isomer and the racemate of ketamine for 10 min. Heart rate, atrioventricular conduction time (AVCT), left ventricular pressure, coronary flow, and inflow and outflow oxygen tensions were measured. Percentage oxygen extraction, oxygen delivery, and oxygen consumption were calculated. RESULTS: Both isomers and the racemate caused a concentration-dependent depression of systolic left ventricular pressure and an increase in AVCT. In the untreated hearts, S(+)-ketamine decreased heart rate and left ventricular pressure and, at higher concentrations, oxygen consumption and percentage oxygen extraction significantly less than R(-)-ketamine independent of blocked or unblocked opioid receptors. Racemic ketamine depressed cardiac function to a degree intermediate to that produced by the isomers. Coronary flow and AVCT were equally affected by the isomers and by the racemic mixture. In the catecholamine depleted hearts both isomers and the racemate caused equipotent depression of all variables. In these hearts cardiac depression was greater, and AVCT, coronary flow, and oxygen delivery were significantly greater than in untreated and opioid receptor-blocked hearts. CONCLUSIONS: Lesser cardiac depression by the S(+) isomer is attributable to an increased availability of catecholamines, because previous depletion of catecholamine stores and autonomic blockade completely inhibited these differences. The inability of cardiac tissue to reuptake released catecholamines into neuronal or extraneuronal sites during exposure to ketamine is stereoselective and caused predominantly by the S(+) isomer. Cardiac opioid receptors are apparently not involved in this phenomenon. PMID- 7793658 TI - Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. IV. Dysrhythmias after sinoatrial node excision. AB - BACKGROUND: Subsidiary atrial pacemakers assume control after sinoatrial (SA) node excision, and anesthetic-catecholamine interactions can produce severe bradycardia during isoflurane anesthesia. We hypothesized that epinephrine enhances atrial, atrioventricular junctional, and ventricular dysrhythmias after SA node excisions in dogs and that inhalation anesthetics would facilitate such dysrhythmias. METHODS: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, at the His bundle, and along the sulcus terminalis. Site of the earliest atrial activation and incidences of nonatrial beats were determined in the conscious state, with methylatropine, with epinephrine, and during halothane, isoflurane, or enflurane anesthesia. RESULTS: After SA node excision, a stable, regular subsidiary atrial pacemaker rhythm resulted. Epinephrine and halothane shifted the site of earliest activation to more remote atrial sites. Epinephrine-induced ventricular escape was increased by all anesthetics tested, but atropine prevented ventricular escape. Epinephrine induced His bundle (atrioventricular junctional) and premature ventricular beats were increased by halothane and enflurane. After SA node excision, ventricular escape occurred as a result of epinephrine-anesthetic interactions, especially during anesthesia with isoflurane. CONCLUSIONS: In dogs with excised SA nodes, anesthetic-catecholamine interaction facilitates ventricular escape, His bundle dysrhythmias, and premature ventricular beats. In addition, halothane and enflurane, more than isoflurane, facilitate ectopic ventricular tachydysrhythmias with epinephrine. Compared to intact dogs, dogs with excised SA nodes may be more susceptible to epinephrine anesthetic dysrhythmias. If findings can be extrapolated to humans, intrinsic SA node dysfunction may facilitate severe cardiac dysrhythmias with inhalation anesthetics and catecholamines. PMID- 7793657 TI - A subtype of alpha 1 adrenoceptor mediates depression of conduction in Purkinje fibers exposed to halothane. AB - BACKGROUND: An action of epinephrine at alpha adrenoceptors has been reported to slow conduction in Purkinje fibers exposed to halothane. In Purkinje fibers one pharmacologically distinguishable alpha 1-adrenoceptor subtype (alpha 1B) sensitive to the noncompetitive antagonist chloroethylcholinidine mediates decreases in automaticity. Another alpha 1 subtype (alpha 1A), sensitive to the competitive antagonist WB4101, increases spontaneous rate and action potential duration by a mechanism thought to involve hydrolysis of membrane phosphoinositides by phospholipase C. This study examined the dose-response relation and receptor-effector mechanisms underlying depression of conduction in canine Purkinje fibers by epinephrine with halothane. METHODS: Conduction velocity was determined in vitro by measuring the conduction time between action potentials recorded from two Purkinje fibers located about 6 mm apart along the length of free running portions of the ventricular conduction system, the false tendons. Velocity was evaluated at 1-min intervals during trials of rapid exposure to different agonists in groups of 6-12 preparations. RESULTS: Epinephrine (0.2-5.0 microM) transiently decreased Purkinje conduction velocity in a dose-related manner by as much as 33% (at 5 microM epinephrine with 0.86 mM (2.8%) halothane). Velocity decreased by 5% (P < or = 0.01) at an epinephrine concentration similar to "just-threshold" dysrhythmogenic plasma epinephrine concentrations (0.2 microM epinephrine with 0.46 mM halothane) reported in halothane-anesthetized dogs. The decreases of conduction velocity were blocked by prazosin but not by metoprolol, were produced by phenylephrine but not by clonidine, and were antagonized by equimolar (0.5 microM) concentrations of WB4101 more so (P < or = 0.01) than by chloroethylclonidine. WB4101 (0.1 microM) produced 87% inhibition of the response to 0.2 microM epinephrine after chloroethylclonidine pretreatment, indicating mediation by the alpha 1A subtype. Other agonists linked to cardiac phospholipase C activation, including endothelin 1 (40 nM) and the muscarinic agonist carbamylcholine (1 mM), also decreased conduction velocity in fibers exposed to halothane. CONCLUSIONS: Clinically relevant concentrations of epinephrine transiently depress conduction in Purkinje fibers exposed to halothane by activating cardiac alpha 1 adrenoceptors, largely but not exclusively the WB4101-sensitive alpha 1A subtype, reportedly coupled to stimulation of phospholipase C and generation of the second messengers diacylglycerol and inositol trisphosphate. Anesthetic potentiation of cardiac alpha 1-adrenoceptor effects may contribute to the generation of halothane epinephrine dysrhythmias by abnormally slowing conduction and facilitating reentry. PMID- 7793659 TI - Halothane restores the altered force-frequency relationship in failing human myocardium. AB - BACKGROUND: The terminally failing human myocardium exerts a negative force frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated. METHODS: Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees C, Ca2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand 125I-CYP. RESULTS: Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 mumol/l) on FFR, and restored the FFR in the presence of ouabain. CONCLUSIONS: Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Ca2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR. PMID- 7793660 TI - The local anesthetic n-butyl-p-aminobenzoate selectively affects inactivation of fast sodium currents in cultured rat sensory neurons. AB - BACKGROUND: Aqueous suspensions of the local anesthetic n-butyl-p-aminobenzoate (BAB), epidurally applied in terminal cancer patients, resulted in a sensory blockade, lasting up to several months. To investigate the mechanism of action on the cellular level, the effect of 100 microM BAB on Na+ action potentials and on Na+ currents in dorsal root ganglion neurons from neonatal rats was studied. METHODS: Small neurons grown in cell culture were selected for patch-clamp measurements. Both Na+ action potentials, evoked by current pulses of increasing amplitude (current clamp) and Na+ currents, activated at different membrane potentials (voltage clamp), were investigated in the absence and presence of 100 microM BAB. The local anesthetic was applied by external perfusion for 2 or 10 min. RESULTS: In the presence of 100 microM BAB, either the firing threshold was raised or the action potential was abolished. The maximal peak conductances, underlying the fast sodium current INa,F and the slow sodium current INa,5, were not changed. However, the inactivation of INa,F was increased by BAB. The sigmoid inactivation curve shifted 12 mV toward hyperpolarizing membrane voltages, whereas no changes were found for the inactivation of the slow Na+ current. Only at short exposure times of 2 min, the effects of BAB could be reversed during a 10-min wash-out. CONCLUSIONS: BAB dramatically increased the firing threshold, and in part of the sensory neurons, it blocked the action potential. The inactivation of the fast Na+ channels, but not of the slow Na+ channels, was increased by BAB. Thus, the block of fast Na+ channels by BAB may contribute to epidural analgesia. At exposure times of 10 min, the effect of BAB was not reversible. This probably originates from its high lipid-solubility, which may be an important factor in determining the duration of the block in vivo. PMID- 7793661 TI - Epidural anesthesia and analgesia. Their role in postoperative outcome. PMID- 7793662 TI - Aerosolized prostacyclin versus inhaled nitric oxide in children with severe acute respiratory distress syndrome. PMID- 7793663 TI - Selective pulmonary vasodilation by inhaled prostacyclin in a newborn with congenital heart disease and cardiopulmonary bypass. PMID- 7793665 TI - Intraoperative hyperkalemia as a triggering mechanism or presenting sign of malignant hyperthermia in two patients with chronic renal failure. PMID- 7793666 TI - Epidural abscess after obstetric epidural analgesia. PMID- 7793667 TI - Unintended transthoracic pulmonary artery cannulation: a complication of central line insertion. PMID- 7793664 TI - Dissection of the posterior pharynx resulting in acute airway obstruction. PMID- 7793668 TI - Intentional occlusion of the right upper lobe bronchial orifice to tamponade life threatening hemoptysis. PMID- 7793670 TI - Negative pressure ventilation during tracheal tube exchange. PMID- 7793669 TI - Postoperative analgesia. PMID- 7793673 TI - Intraoperative transcranial Doppler monitoring. PMID- 7793671 TI - Postanesthesia care unit costs. PMID- 7793672 TI - Nasal midazolam in children. PMID- 7793674 TI - Syringe cap prevents leaks during one-lung ventilation. PMID- 7793675 TI - Peri- or postoperative ulnar neuropathy? PMID- 7793676 TI - Should the government continue to fund basic biomedical research? PMID- 7793677 TI - Central cholinergic stimulation causes miosis. PMID- 7793678 TI - Timing of elective surgery after coronary angioplasty. PMID- 7793679 TI - Relations between genetic distance of parental pig breeds and heterozygosity of their F1 crosses measured by genetic markers. AB - The aim of this paper is to examine the extent to which increment of heterozygosity in F1 crosses can be predicted from genetic distance of parental breeds. For this purpose, 38 polymorphic marker loci (blood groups, allotypes, polymorphic proteins and enzymes) were tested in 1115 purebred animals (Duroc, Hampshire and Czech Meat Pig as sire breeds; Landrace, Large White and Black Pied Prestice as dam breeds) and in 1428 crossbred animals of the resulting nine crossbred groups. The number of animals in each genetic group ranged from 75 to 230. On the basis of the allele frequencies of the scored loci, three measures of genetic diversity (heterozygosity, standardized heterozygosity, effective number of alleles) were calculated in all 15 genetic groups. Furthermore, two measures of genetic distance (Nei's standard genetic distance and Gregorius' absolute genetic distance) were calculated between the parental populations. High correlations (Pearson product-moment correlation 0.62 to 0.73; Spearman rank correlation 0.58 to 0.85) were found between the increment of heterozygosity in the crosses (in relation to the mean of the heterozygosities of parental populations) and the genetic distance between the parental populations. PMID- 7793680 TI - Organization of the sex-linked late-feathering haplotype in chickens. AB - Nucleotide sequence analysis of polymerase chain reaction products confirmed that ev21 integrated into one of two large homologous elements on the Z chromosome of late-feathering (LF) White Leghorn chickens. Southern blots of NotI-, NaeI-, KspI and BamHI-digested DNA from early-feathering (EF) and LF White Leghorns, that had been hybridized with a probe that flanks ev21, indicated a 180 kb duplication of an unoccupied repeat in the LF genotype of White Leghorns. A KspI fragment that carries ev21 was about 32 kb smaller than the KspI fragment found in EF DNA. In the evolution of LF, retroviral insertion into one of two large repeats and a 32 kb deletion may have generated LF. PMID- 7793681 TI - Sequence and PCR-RFLP analysis of 14 novel BoLA-DRB3 alleles. AB - The genetic diversity of the bovine class II DRB3 locus was investigated by polymerase chain reaction (PCR) amplification and DNA sequencing of the first domain exon. Studying 34 animals of various cattle breeds, 14 previously unrecognized DRB3 alleles were identified. In three alleles, amino acid substitutions were observed that had not been previously found in bovine DRB3, but occurred at the same position in bovine DQB and in the DRB alleles of other mammals. For all newly identified alleles, the restriction fragment length polymorphism (RFLP) patterns of PCR products obtained with the enzymes RsaI, BstYI, and HaeIII were compared with patterns of 38 previously described alleles. Altogether, eleven novel PCR-RFLP types were defined. Twelve out of the 42 PCR RFLP types identified so far were not found to be fully informative because they corresponded to more than one allelic sequence. PCR-RFLP may therefore be a rapid and useful method for DRB3 typing in cattle families, but for studies on outbred populations, sequencing and hybridization techniques are required. PMID- 7793682 TI - Probability of random sire exclusion using microsatellite markers for parentage verification. AB - Many microsatellite sequences have been described in the bovine genome. Being highly polymorphic these have been suggested as markers for parentage verification and individual identification in cattle. We have evaluated the use of five highly polymorphic microsatellite markers for parentage verification in 14 breeds of cattle in the UK. Three of the microsatellite loci occur within introns in genes: BoLA DRB3, steroid 21-hydroxylase, and the beta subunit of the follicle-stimulating hormone. The other two are anonymous sites ETH131 and HEL6. Results were analysed by a statistical approach that takes in to account deviations from Hardy-Wienberg equilibrium and linkage disequilibrium for multiple loci. The method of determining the probability of random sire exclusion uses observed genotype frequencies instead of allele frequencies. Independently, the markers used have a probability of between 0.72 and 0.62 of identifying a parentage error, while used together the five markers give, on average across breeds, a probability of 0.99 of excluding an incorrect sire. PMID- 7793684 TI - Five regional localizations to the sheep genome: first assignments to chromosomes 5 and 12. AB - The regional localization of five reference loci to sheep chromosomes is reported. The newly mapped loci are the T-cell receptor, beta (TCRB), coagulation factor X (F10), laminin gamma 1 (LAMC1), cyclic GMP rod phosphodiesterase, alpha (PDEA) and fibroblast growth factor 2 (FGF2). The assignments of PDEA and LAMC1 to chromosomes 5q23-q31 and 12q22-q24 respectively provide the first markers physically assigned to these chromosomes. They also allow the provisional assignment of sheep syntenic group U19 to chromosome 5 and U1 to chromosome 12. The mapping of FGF2 to chromosome 17q23-q25 anchors the unassigned linkage group 'A' to chromosome 17, and the assignment of TCRB to chromosome 4q32-qter facilitates the orientation of a linkage group on sheep chromosome 4. The mapping of F10 to sheep chromosome 10q23-qter supports the recent assignment of bovine syntenic group U27 to cattle chromosome 12, as sheep chromosome 10 and cattle chromosome 12 are banded homologues. PMID- 7793683 TI - Genetic characterization of highly inbred chicken lines by two DNA methods: DNA fingerprinting and polymerase chain reaction using arbitrary primers. AB - Thirteen highly inbred chicken lines were analysed at the DNA level by DNA fingerprinting (DEP) and by polymerase chain reaction (PCR) using random primers. In general, the DFP patterns of individuals within a line were identical. The DFP band-sharing (BS) values among lines from different breeds (Leghorn, Fayoumi, Spanish) ranged from 0.10 to 0.20. The DFP BS values among Leghorn lines from different genetic backgrounds ranged from 0.42 to 0.79. The DFP BS values among lines selected for different major histocompatibility complex serotypes from a common genetic background ranged from 0.70 to 0.95. Some randomly amplified polymorphic DNA (RAPD) PCR products were specific to a single line, some to all lines from the same genetic base, and some to all lines from the same breed. The RAPD-PCR band-sharing values ranged from 0.66 to 0.99 for all between-line comparisons. Thus, the ability to detect biodiversity at the DNA level was greater in this study for DFP than for RAPD-PCR. The possible origin of line specific bands, relative advantages of detecting biodiversity by using different molecular screening techniques and uses of highly inbred chicken lines in molecular analysis are discussed. PMID- 7793685 TI - Synteny-mapping horse microsatellite markers using a heterohybridoma panel. AB - A panel of horse-mouse heterohybridoma cells was tested for genetic markers using biochemical and polymerase chain reaction-(PCR-) based tests. Biochemical markers included phosphoglucomutase (PGM), glucose phosphate isomerase (GPI) and 6 phosphogluconate dehydrogenase (PGD). Markers detected using PCR-based tests included microsatellite markers HTG2-15, HMS 1-3, 5-8, VHL20, ECA2 and genes for equine major histocompatibility gene ELA-DRA, tumour necrosis factor alpha (TNFA) and transferrin. The results were analysed for correlation and concordance. Based on the results, five synteny groups were identified, specifically between ELA DRA, TNFA, HMS5 and HTG5; between HTG3 and HTG13; between HTG4, HTG8 and HMS3; between HTG6 and HMS1; and between HTG7, HTG9 and HMS6. Evidence was also found for synteny between HTG12, HMS7 and ECA2, however, confirmation requires further testing. Cytogenetic evaluation of the cell lines making up the panel indicated that large metacentric chromosomes were preferentially lost or tended to break at the centromere. Consequently, the results from this analysis can be used to identify synteny, but not to exclude synteny. PMID- 7793686 TI - Long-range mapping of the calcium release channel and glucosephosphate isomerase loci using pulsed-field gel electrophoresis. AB - Long range restriction maps of the calcium release channel (CRC) and glucosephosphate isomerase (GPI) loci have been constructed using pulsed field electrophoresis, Southern blotting and CRC- and GPI-specific probes. The maps, deduced from the restriction fragments detected by the probes, covered 1.1 and 0.3 Mb respectively and no overlap between the maps of these closely linked loci was detected. The minimal distance between the GPI and CRC loci was estimated to be at least 500 kb. PMID- 7793687 TI - Genetic analysis of three loci homologous to human G9a: evidence for linkage of a class III gene with the chicken MHC. AB - The cDNA clones of two newly discovered genes in the class III region of the human major histocompatibility complex (MHC) were hybridized to chicken DNA. One of these cDNA clones (pG9a-4C7), which detects the single-copy human G9a (BAT8) gene, gave a repeatable restriction pattern. This heterologous cDNA clone was used to detect and map three different PstI restriction fragment length polymorphisms among the two internationally recognized chicken reference populations. Two of the loci were unlinked to previously mapped markers, but one polymorphism cosegregated with the EaB locus in the Compton mapping population. These results provide evidence that some genes of the mammalian class III region, such as G9a, may be linked to the MHC in chickens. PMID- 7793688 TI - A rapid PCR-based test for the endogenous viral element ev3 of chickens. AB - A short fragment of chicken genomic DNA encompassing the insertion site of the endogenous avian leucosis viral element ev3 was isolated using the inverse polymerase chain reaction (inverse PCR) technique. The nucleotide sequence of the unoccupied site was used to design PCR primers that can be used to unambiguously determine the genetic status of any chicken, with respect to ev3. Screening of a small number of individuals from exotic breeds of chickens suggested that the frequency of ev3 is highly variable. The ev3 integration site shows a high degree of sequence homology with the macrophage-specific tyrosine kinase gene, bmk, in mice. PMID- 7793689 TI - Extensive mtDNA diversity in horses revealed by PCR-SSCP analysis. AB - The hypervariable D-loop region of mitochondrial DNA (mtDNA) was amplified with the polymerase chain reaction using total horse DNA samples. Analysis of single strand conformation polymorphism (SSCP) of denatured amplification products was carried out by native polyacrylamide (8%) gel electrophoresis followed by silver staining. As many as 15 distinct SSCP variants were revealed when screening a total of 78 maternally unrelated horses representing five different breeds. All breeds showed a high degree of polymorphism and the estimated probability (PImt) that two maternally unrelated individuals have, by chance, identical SSCP variants varied between 0.14 and 0.30. We detected no heteroplasmy or deviations from strict and stable maternal inheritance when examining four maternal lineages, each represented by six to eight horses, separated by up to five generations from a common ancestral mare. The study establishes a simple screening method for detecting equine mtDNA types, which can be applied for tracing maternal genealogies and for association studies. PMID- 7793690 TI - Two new variants of the bovine PAS-1 glycoprotein. AB - Two new alleles (A and E) of the bovine MUC locus which encodes PAS-1 protein, a glycoprotein of the milk fat globule membrane, are reported. The A allele was found in Italian Brown while E was present in the Jersey and the Piedmont breeds. PMID- 7793691 TI - Comparative mapping of sheep inhibin subunit beta b to chromosome 2 in sheep and cattle by fluorescence in situ hybridization. AB - A cosmid clone containing the complete sheep inhibin subunit beta B gene (INHBB) was assigned to sheep and cattle homologous chromosome bands 2q31-q33 by fluorescence in situ hybridization. The assignment of INHBB in sheep excludes another candidate gene as the site of the FecB mutation. PMID- 7793692 TI - Bovine microsatellite dinucleotide repeat polymorphisms at the TEXAN11, TEXAN12, TEXAN13, TEXAN14 and TEXAN15 loci. PMID- 7793693 TI - Dinucleotide repeat polymorphisms at the bovine HUJ673, HUJ121, HUJ174, HUJ225, HUJI13 and HUJI29 loci. PMID- 7793696 TI - HincII and HaeIII RFLPs in the porcine mtDNA D-loop region. PMID- 7793694 TI - TXQG1: a polymorphic microsatellite on bovine chromosome 10. PMID- 7793695 TI - DNA polymorphisms in two transcription control elements (SP1- and TATA-box) of porcine HSP70.2 gene detected by allele-specific PCR. PMID- 7793697 TI - Four SINE-associated polymorphic bovine microsatellites (HEL23-HEL26). PMID- 7793698 TI - A PCR-RFLP marker for the erythroid aminolevulinate synthase gene (ALAS2) on canine chromosome X. PMID- 7793699 TI - BglII and HincII detect polymorphisms at porcine GPI locus. PMID- 7793700 TI - Bovine microsatellite dinucleotide repeat polymorphisms at the TEXAN16, TEXAN17, TEXAN18, TEXAN19 and TEXAN20 loci. PMID- 7793701 TI - Polymorphic bovine microsatellites INRAMTT178, INRAMTT180 and INRAMTT183. PMID- 7793702 TI - A SstI RFLP at the chicken transforming growth factor-beta 2 locus (TGFB2). PMID- 7793703 TI - Mapping the CdxA gene to a new linkage group in chicken. PMID- 7793705 TI - A BglII polymorphism at the porcine INHBB locus. PMID- 7793704 TI - A BglII polymorphism at the porcine transferrin (TF) locus. PMID- 7793706 TI - A MnlI polymorphism at the bovine alpha s2-casein gene. PMID- 7793708 TI - Rollerblades. PMID- 7793707 TI - Sensitivity of the Ottawa rules. AB - STUDY OBJECTIVE: To validate criteria predicting ankle and mid-foot fractures with 100% sensitivity. DESIGN: Prospective validation study SETTING: A 929-bed community teaching hospital with an annual census of 76,488 ED visits. PARTICIPANTS: Convenience sample of patients older than 18 years with acute ankle or midfoot injury. INTERVENTIONS: Radiography was performed in each patient received after pertinent history and physical examination findings were recorded. RESULTS: Five hundred seventy radiographs were obtained in 484 patients. Four hundred twenty-one were of the ankle, and 149 were of the foot. There were 93 ankle fractures and 29 midfoot fractures, giving a fracture yield of 22.1% for ankle films and 19.5% for foot films. Decision rules had sensitivity of 94.6% and specificity of 15.5% for ankle fractures and sensitivity of 93.1% and specificity of 11.5% for midfoot fractures. Prospective criteria failed to predict fracture in five of the ankle group and two of the midfoot group. Physicians predicting fracture solely on the basis of clinical suspicion had a sensitivity of 69% in ankle injuries and 76% in midfoot injuries. CONCLUSION: We were unable to validate with 100% sensitivity the Ottawa rules predicting ankle and midfoot fractures. However, the Ottawa rules were more sensitive than clinical suspicion alone. PMID- 7793709 TI - Chest pain treatment center. PMID- 7793711 TI - Terbutaline sulfate overdose. PMID- 7793710 TI - Practice of procedures on the newly dead. PMID- 7793712 TI - Fatal serotonin syndrome with trismus. PMID- 7793713 TI - Endotracheal tube placement. PMID- 7793714 TI - Recognition and evaluation of oncology-related symptoms in the emergency department. AB - STUDY OBJECTIVE: To identify the oncology patient population presenting to the emergency department and examine the causes and clinical management of oncology symptoms in the ED. DESIGN: Retrospective review of 5,640 adult patients, with the following variables identified for oncology patients presenting to the ED: age, sex, cancer type, cancer stage, previous cancer treatment, previous hospitalization, presenting symptoms, treatment provided in the ED, admission and discharge data, and day, time, and length of ED visit. SETTING: Community teaching hospital with annual ED census of 31,000. PARTICIPANTS: All adult oncology patients who presented to the ED during the study period. We identified these patients by cross-referencing ED logs and tumor registry records. RESULTS: Cancer history was identified for 284 of the 5,640 adult ED admissions (5%). Forty-three percent (n = 122) of the 284 patients with cancer history had an oncology-related ED visit. The most common symptoms of these patients were gastrointestinal (48%), pain (40%), neurologic (38%), cardiac (25%), and pulmonary (23%). Ten percent of patients with oncology-related ED visits died during the admission, and 48% died within 1 year of the ED visit. CONCLUSION: Oncology patients present to the ED with symptoms of undiagnosed malignancy, complications of cancer treatment, and acute disease-related symptoms. Knowledge of an individual's cancer history and ability to recognize oncologic symptoms are important to the management of oncology patients. PMID- 7793715 TI - Fever in geriatric emergency patients: clinical features associated with serious illness. AB - STUDY OBJECTIVE: To determine the clinical significance of fever in geriatric emergency department patients. DESIGN: Case series with follow-up. SETTING: Urban, university-affiliated community hospital. PARTICIPANTS: Consecutive patients over the age of 65 years who presented to the ED during a 12-month period with an oral temperature of 100.0 degrees F (37.8 degrees C) or higher. RESULTS: We considered the following features indicators of serious illness: positive blood culture(s), related death within 1 month of ED visit, need for surgery or other invasive procedure, hospitalization for 4 or more days, IV antibiotics for 3 or more days, and repeat ED visit within 72 hours for related condition. Four hundred eighty-nine patients were eligible for study. Of the 470 patients with complete follow-up data, 357 (76.0%) had indicators of serious illness. Clinical features found to be independently associated with serious illness included oral temperature of 103 degrees F (39.4 degrees C) or more, respiration rate of 30 or more, leukocytosis of 11.0 x 10(9)/L or more, presence of an infiltrate, and pulse of 120 or more. At least one indicator of serious illness was present in 63 of 128 patients (49.6%) with none of these independently predictive clinical features. The most common final diagnoses were pneumonia (24.0%), urinary-tract infection (21.7%), and sepsis (12.8%). CONCLUSION: Fever among geriatric ED patients frequently marks the presence of serious illness. All such patients should be strongly considered for hospital admission, particularly when certain clinical features are present. The absence of abnormal findings does not reliably rule out the possibility of serious illness. PMID- 7793717 TI - Pain and tissue-interface pressures during spine-board immobilization. AB - STUDY OBJECTIVES: Although spine boards are one of the main EMS means of immobilization and transportation, few studies have addressed the discomfort and potential harmful consequences of using this common EMS tool. We compared the levels of pain and tissue-interface (contact) pressures in volunteers immobilized on spine boards with and without interposed air mattresses. DESIGN: Prospective crossover study. SETTING: Emergency department of Methodist Hospital of Indiana, Indianapolis, Indiana. PARTICIPANTS: Twenty healthy volunteers who had not taken any analgesic drugs in the preceding 24 hours, were not experiencing any pain at the time of the study, and did not have history of chronic back pain. INTERVENTIONS: To simulate prehospital transport conditions, we immobilized volunteers with hard cervical collars and single-buckle chest straps on wooden spine boards with or without commercially available medical air mattresses. The crossover order was randomized. After 80 minutes, immobilization measures were discontinued and the subjects were allowed to get off the boards for a recovery period of 60 minutes. Subjects were then studied for a second 80-minute period with the opposite intervention. At baseline and at 20-minute intervals, the level of pain was rated with a 100-mm visual analog scale. Tissue-interface pressures were measured at the occiput, sacrum, and left heel. RESULTS: Mean pain on the visual analog scale was 9.7 mm at the end of the mattress period and 37.5 mm at the end of the no-mattress period (P = .0001). Although there were no significant differences in pain between the two groups at time 0, volunteers reported significantly more pain during the no-mattress period at 20 (P = .003), 40 (P = .0001), and 60 minutes (P = .0001). All 20 subjects reported that immobilization on the spine board with the mattress was "much better" (five-point scale) than that without the mattress. Interface pressure levels were significantly less in the mattress period than in the no-mattress period measured at occiput (P = .0001), sacrum (P = .0001), and heel (P = .0001). CONCLUSION: In a simulated immobilization experiment, healthy volunteers reported significantly less pain during immobilization on a spine board with an interposed air mattress than during that on a spine board without a mattress. Tissue-interface pressures were significantly higher on spine boards without air mattresses. This and previous studies suggest that immobilization on rigid spine boards is painful and may produce tissue-interface pressure high enough to result in the development of pressure necrosis ("bedsores"). Emergency care providers should consider the use of interposed air mattresses to reduce the pain and potential tissue injury associated with immobilization on rigid spine boards. PMID- 7793716 TI - Three-rescuer CPR: the method of choice for firefighter CPR? AB - STUDY OBJECTIVE: To compare the quality of CPR provided by firefighters performing three-rescuer CPR with that achieved by firefighters trained to provide standard two-rescuer CPR. DESIGN: Eight months after training a large number of firefighters to perform three-rescuer CPR, we used a quasi-experimental design to compare the performance of a randomly selected subset of these companies to that achieved by a control group of engine companies that received refresher training in standard two-rescuer CPR. Both groups used bag-valve masks to provide rescue ventilations. Testing was conducted on a no-notice basis with a recording mannequin. Key actions were scored by an experienced observer using explicit pass-fail criteria. Mannequin-generated strip charts were used to calculate the rate and depth of chest compressions and the ventilatory rate, volume, and minute ventilation in a blinded manner. SETTING: Fire stations of the Memphis Fire Department. The department is the sole provider of first-responder emergency care to the citizens of Memphis, Tennessee (population, 610,000). RESULTS: Three-rescuer teams delivered a mean minute ventilation substantially greater than that produced by two-rescuer teams (7.7 +/- 5.3 L versus 4.9 +/- 4.2 L, P < .001). Intergroup differences in the mean depth of chest compressions were less marked, but they were still significant (17.2 +/- 8.3 mm of recorder-needle deflection versus 13.7 +/- 7.0 mm, P < .001). CONCLUSION: Three rescuers can produce better CPR than two when a bag-valve-mask device is used. The technique is easily learned and readily retained. PMID- 7793719 TI - Hyponatremia as the cause of seizures in infants: a retrospective analysis of incidence, severity, and clinical predictors. AB - STUDY OBJECTIVES: (1) To determine the incidence of hyponatremic seizures in infants, (2) to compare the severity and outcome of seizures in hyponatremic and normonatremic patients, and (3) to evaluate the utility of clinical predictors of hyponatremia. DESIGN: Retrospective chart review of infants who presented to an urban pediatric emergency department from 1988 through 1993. PARTICIPANTS: Patients who experienced seizures while in the ED. These patients were divided into hyponatremic and normonatremic groups. RESULTS: Hyponatremia was the cause of seizures in 70% of 47 infants younger than 6 months who lacked other findings suggesting a cause. Median seizure duration was longer in hyponatremic patients (30 versus 17 minutes; P = .007), with a greater incidence of status epilepticus (73% versus 36%; P = .02) and fewer patients with seizures lasting less than 10 minutes (9% versus 36%; P = .04). Emergency intubation was performed more often in hyponatremic patients (12% versus 0%; P = .009). The median temperature was lower in hyponatremic infants than in normonatremic patients (35.5 degrees C versus 37.2 degrees C; P = .0001). Exact logistic-regression methods identified temperature of 36.5 degrees C or less as the best predictor of hyponatremic seizures, with an OR of 64 (95% CI, 8 to 1,026). CONCLUSION: Hyponatremia should be strongly suspected in an infant less than 6 months old with seizures and a temperature of 36.5 degrees C or less. PMID- 7793718 TI - Pediatric basilar skull fracture: do children with normal neurologic findings and no intracranial injury require hospitalization? AB - STUDY OBJECTIVE: To delineate complications in patients with basilar skull fractures (BSFs) and normal neurologic findings, including computed tomography (CT) scans without intracranial injury, and to assess the need for hospitalization. DESIGN: Retrospective chart review. PARTICIPANTS: All emergency department patients with the ED diagnosis or hospital discharge diagnosis of BSF. Patients were included if they had a clinical or radiographic diagnosis of BSF. A subgroup of patients ("simple BSF") with normal neurologic examination findings in the ED, Glasgow Coma Scale scores of 15, and cranial CT scans without intracranial pathology was specifically analyzed. RESULTS: We included 239 patients in the study. One hundred fourteen patients (48%) were included in the "simple BSF" subgroup. In this subgroup, vomiting (6%) was the most common complication, meningitis (1%) the most serious. There were no cases of delayed intracranial hemorrhage, and no patient with "simple BSF" required surgery. CONCLUSION: Given the relatively low frequency of serious complications, our study suggests that some patients with BSFs may not require hospital admission. PMID- 7793720 TI - The temporal profile of increased transaminase levels in patients with acetaminophen-induced liver dysfunction. AB - STUDY OBJECTIVE: It is often taught that acetaminophen-induced liver dysfunction occurs only after a latent period of 24 to 48 hours. This study was designed to evaluate the temporal profile of transaminase levels in patients with acetaminophen-induced hepatotoxicity. DESIGN: Prospective data collection using standard poison control center data sheets. PARTICIPANTS: Hospitalized patients with acetaminophen exposure who were reported to the Long Island Poison Control Center between January 1993 and June 1994. Patients who presented within 24 hours of ingestion and in whom increased aspartate aminotransferase (AST) levels developed during hospitalization were included in the data analysis. Patients who presented more than 24 hours after ingestion, who had ingested another potentially hepatotoxic agent, or who had ingested acetaminophen over a period of more than 2 hours were excluded. RESULTS: Of 1,825 patients with reported acetaminophen exposure, 779 had potentially toxic ingestions and were examined in an emergency department. Of 291 patients with toxic acetaminophen levels who were admitted, 36 (12%) had increased levels of AST at some point during hospitalization. All received oral N-acetylcysteine within 2.5 hours of presentation. In 11 of 19 patients who met all inclusion criteria (58%), AST levels were noted to be increased in the 24 hours after ingestion. The median peak AST level was 422 IU/L (range, 74 to 8,538 IU/L). AST levels peaked within 48 hours in 4 patients (21%) and within 72 hours in 18 patients (95%). Six of eight patients with peak AST levels greater than 1,000 IU/L had increased transaminase levels during the 24 hours after acetaminophen ingestion. CONCLUSION: Acetaminophen poisoning may cause the serum transaminase level to increase during the 24 hours after ingestion. PMID- 7793721 TI - Iron overdose and detection of gastrointestinal bleeding with the hemoccult and gastroccult assays. AB - STUDY OBJECTIVE: To determine the ability of the Hemoccult and Gastroccult tests (SmithKline Diagnostics) to detect blood in vitro in whole-bowel irrigation (WBI) solution. INTERVENTIONS: One tablet of ferrous gluconate 324 mg, ferrous sulfate 325 mg, or ascorbic acid 500 mg; or one Materna prenatal vitamin tablet (Lederle Laboratories) was dissolved in 30 mL of Colyte. Colyte alone and each test solution were tested with Hemoccult and Gastroccult slides, then retested at pH values of 3 and 8. Fresh solutions were then spiked with blood and tested with Gastroccult slides. Materna and ascorbic acid solutions were spiked with blood, then tested with Hemoccult slides. RESULTS: Positive results were difficult to detect on Gastroccult slides. Hemoccult slides were falsely positive for solutions containing only iron and falsely negative for blood-spiked samples containing ascorbic acid. CONCLUSION: Both the Hemoccult and Gastroccult tests may be unreliable in detecting GI bleeding in cases of iron overdose treated with WBI. PMID- 7793722 TI - Does a sodium-free buffer affect QRS width in experimental amitriptyline overdose? AB - STUDY OBJECTIVES: We carried out this study to determine the effects of pH alteration on QRS width with administration of tromethamine, a non-sodium containing buffering agent, in experimental amitriptyline overdose. DESIGN: Prospective, nonblinded trial. PARTICIPANTS: Adult mongrel dogs. INTERVENTIONS: Pentobarbital-anesthetized dogs were overdosed with amitriptyline 5 mg/kg followed by infusion at 1.0 mg/kg/minute until the QRS width doubled, then decreased to .5 mg/kg/minute until the end of the experiment. At two defined points of toxicity, the dose of tromethamine required to raise the pH to 7.50 +/- 4 was given. pH and QRS width at a speed of 100 mm/second were measured over a 30 minute period after each tromethamine dose. Data were analyzed with non-linear regression analysis. RESULTS: At toxicity 1 the mean pH was 7.32, with a QRS width of 11.6 mm. Two minutes after the tromethamine dose the pH rose to 7.51, with narrowing of the QRS width to 8.4 mm. At toxicity 2 the pH was 7.40, with QRS width of 10.6 mm. Two minutes after tromethamine, the pH rose to 7.49 and the QRS width decreased to 9.7 mm. Regression analysis showed a correlation between pH and QRS width; as pH increased, QRS width decreased (P = .0001). CONCLUSION: Cardiac toxicity of amitriptyline overdose, as manifested by QRS widening, is reversible by pH changes alone. PMID- 7793723 TI - Factors associated with relapse after emergency department treatment for acute asthma. AB - STUDY OBJECTIVE: The rate of relapse after emergency department treatment for acute asthma is high. Most studies on this subject were performed before the recent recommendations for routine use of corticosteroids and followed the patients for 10 or fewer days. We sought to evaluate relapse following ED treatment for acute asthma over a longer period, focusing particularly on the relationship between steroid use and outpatient follow-up visits. DESIGN: A prospective study in which we followed patients for 21 days after discharge to determine their relapse rate (unscheduled return for asthma treatment) and compliance with scheduled outpatient appointments. SETTING: University-affiliated county hospital ED. PARTICIPANTS: One hundred four adult asthmatic patients discharged from our ED after treatment under a standardized protocol. RESULTS: Follow-up was performed for 91 patients (88%). There was no difference in the posttreatment forced expiratory volume at 1 second between those who relapsed (55.2%) and those who did not (57.8%; NS). Twenty-three patients (25.3%) relapsed within 3 weeks of discharge. Ninety-one percent of relapses occurred before the patients saw their primary care physician. Those who relapsed had a history of previous ED visits and hospitalizations. There was no difference in theophylline levels or history of cigarette use. Patients who relapsed within 3 days had higher eosinophil counts. CONCLUSION: Even with routine use of oral corticosteroids, a high percentage of patients relapse after ED treatment for acute asthma. Patients who relapse have a greater number of recent ED visits and so should be targeted for more aggressive management of their asthma. PMID- 7793725 TI - ECG diagnosis of acute myocardial infarction in the presence of left bundle branch block in patients undergoing continuous ECG monitoring. AB - It is common knowledge that the ECG diagnosis of completed myocardial infarction in the presence of left bundle-branch block (LBBB) is extremely difficult and often impossible. More than 50 rules have been proposed as criteria for interpreting Q-wave equivalents superimposed on the QRS complex in the presence of LBBB. However, because of misinterpretation of the available literature, physicians frequently recommend that patients with chest pain in the presence of LBBB receive thrombolytic therapy or urgent coronary arteriography on the basis of the assumption that acute injury and ischemia cannot be interpreted in the presence of LBBB. Unfortunately, many physicians fail to realize that although completed infarction is difficult to confirm in the presence of LBBB, ongoing ischemia and injury can be detected in the presence of LBBB and may be seen as often as they are in the presence of normal cardiac conduction. A deflection of the J point (and ST segment) in the direction of the major QRS complex or an elevation of the ST segment of more than 7 to 8 mm opposite the direction of the major QRS complex has been demonstrated to have a sensitivity of more than 50% in detecting acute injury, with a specificity of more than 90%. During the first half of an ongoing prospective study of the use of continuous 12-lead ECG monitoring in the emergency department, we encountered five patients with final diagnoses of acute myocardial infarction in the presence of LBBB who demonstrated significant ECG changes while undergoing continuous ST-segment monitoring with frequent serial ECGs. The five different locations of the infarcts in these five patients were posterior, posterolateral, inferior, anterior, and anterolateral. We present these patients' cases to demonstrate the ECG characteristics of acute injury in the presence of LBBB. PMID- 7793724 TI - Anticonvulsant effects of intracerebroventricular adenocard in theophylline induced seizures. AB - STUDY OBJECTIVE: To evaluate the potential anticonvulsant effects of Adenocard in theophylline-induced seizures, we developed a rodent model of theophylline neurotoxicity with resultant convulsions. We used this model to investigate the actions of intracerebroventricular (ICV) Adenocard on seizure onset. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Surgical cannulation of the jugular veins of the rats was followed by stereotaxic placement of a catheter in the right lateral ventricle. The rats then received 15 micrograms (5 microL) ICV Adenocard or an equivalent. Ten seconds later, continuous infusion of IV aminophylline was begun at a rate of 75 mg/minute until the appearance of generalized convulsions with maximal hindlimb extension. RESULTS: Compared with vehicle-injected controls, rats that received ICV Adenocard had a significant delay in mean time to seizure (162.1 seconds versus 107.4 seconds; P < .001). There was a corresponding increase in the weight-adjusted convulsant dose of aminophylline after the ICV administration of Adenocard (311.4 mg/kg versus 470.4 mg/kg; P < .003). CONCLUSION: Our data indicate that ICV Adenocard ameliorates theophylline-induced seizures. Potential anticonvulsant benefits of Adenocard and other adenosinergic compounds for victims of severe theophylline poisoning should be investigated further. PMID- 7793727 TI - Subarachnoid hemorrhage: an unusual presentation of shock. AB - A 42-year-old woman became profoundly hypotensive shortly after arriving at our emergency medical center after a seizure. The patient's blood pressure did not respond to aggressive fluid resuscitation, administration of inotropic agents, vasopressors, or corticosteroids. After a thorough search for the cause of shock, she was found to have a subarachnoid hemorrhage (SAH). Hypotension is a rare occurrence in SAH. Several mechanisms of SAH are reviewed in this report and are invoked to explain this patient's lack of response to the standard therapies for hypotension. Emergency physicians should consider SAH in the differential diagnosis of refractory shock in patients who present with neurologic abnormalities. PMID- 7793726 TI - Moonlighting. PMID- 7793729 TI - Warfarin sodium-induced skin necrosis. AB - Skin necrosis is a rare complication of treatment with coumarin derivatives. Since it was first identified by Verhagen in 1952, approximately 200 cases of skin necrosis have been reported worldwide, but only 73 have been reported in the English language literature. A telltale clinical scenario of pain and petechiae progressing to sharply demarcated ecchymosis, bullae formation, and gangrenous necrosis manifests most often in the adipose tissues of middle-aged women. Necrosis usually appears within 3 to 6 days of the initiation of warfarin sodium therapy. We report a case of cutaneous necrosis that began 46 days after warfarin sodium therapy was begun. PMID- 7793728 TI - Anterior spinal artery infarction. AB - Spinal cord ischemia, as represented by acute paraplegia, is rare in the absence of trauma. It is even more uncommon that an infarction of the spinal cord occurs in a patient with no predisposition to vascular disease. We report a case of anterior spinal artery syndrome resulting from an infarction of the anterior aspect of the spinal cord in an otherwise healthy 45-year-old woman. PMID- 7793731 TI - Fertilizing the spirit of Hippocrates. PMID- 7793730 TI - Ventricular tachycardia may masquerade as supraventricular tachycardia in patients with preexisting bundle-branch block. AB - We present the cases of three patients with preexisting bundle-branch block in whom wide-complex tachycardias were considered to be of supraventricular origin because QRS morphologies were essentially unchanged from those during normal sinus rhythm. The patients experienced adverse effects from medications for supraventricular tachycardia. Ventricular tachycardia eventually was diagnosed in all three by means of invasive electrophysiologic studies. Ventricular tachycardia may masquerade as supraventricular tachycardia in patients with fixed intraventricular conduction disturbance. Emergency therapy based solely on the QRS identity criteria may result in poor clinical outcome. PMID- 7793732 TI - Carotid endarterectomy based on preoperative duplex ultrasound. AB - Recent studies have suggested that carotid endarterectomy can be performed safely based solely on the noninvasive duplex ultrasound evaluation in selected patients. We have prospectively evaluated 60 consecutive patients who underwent 65 carotid endarterectomies, 48 patients without preoperative angiography and 12 with angiography. Forty-two patients were operated on for symptomatic disease, and 23 procedures were done for critical, asymptomatic stenoses. Long term followup consisted of physical examination and serial duplex scans every 3-6 months postoperatively over a mean followup period of 2.4 years. Clinical management indicated by duplex ultrasound was altered in only one of the 12 patients who had preoperative angiography, a change in the timing of the endarterectomy in a symptomatic patient with an ulcerated lesion seen at angiography. At operation the severity of disease predicted by duplex ultrasound was confirmed in all cases (100 per cent sensitivity), including one > 80% diameter stenosis interpreted by angiography as occluded; no unsuspected anatomic anomalies were found at surgery. The duplex scan also correlated well with intraoperative findings of surface ulceration and gross intraplaque hemorrhage. There was one intraoperative stroke with good recovery in a patient with preoperative angiography; and there were no deaths, for a combined morbidity and mortality of 1.6 per cent. During long term followup, 97 per cent of patients have remained symptom-free. We conclude that clinical assessment with a preoperative duplex ultrasound scan of good technical quality and interpreted in collaboration with the vascular surgeon provides appropriate information on which to base carotid endarterectomy and allows a safe alternative to the routine use of preoperative angiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793733 TI - Rupture of known abdominal aortic aneurysms: an ethical dilemma. AB - Elderly patients with abdominal aortic aneurysms (AAA) may be deemed inoperable due to the presence of comorbid conditions. Presentation of these patients with acute rupture can then result in difficult ethical decisions regarding surgical treatment. Over six years, 80 patients were treated emergently for ruptured AAA. Of these patients, 26 (32.5%) had known aneurysms. This study was performed to determine outcome and factors affecting mortality in patients with known AAAs. There were no significant differences between known and unknown AAA groups with regard to operative risk. In the overall group (n = 80), patient delay in seeking treatment averaged 20.4 hours with a trend towards shorter times in those with known AAAs (13.8 hours) compared with the unknown group (23.6 hours; p = 0.09). Medical transport delay, however, was significantly shorter for patients with known AAA (124 minutes versus 230 minutes; p = 0.04). Overall mortality was 56 per cent (n = 45). Those patients with known AAAs had a higher mortality (69%; n = 18) than those with unknown AAAs (50%, n = 27) but this was not statistically significant (P = 0.10). In patients with known AAAs, operative death was related to patient delay, with an average delay in seeking medical advice of 21.3 hours in nonsurvivors compared with 8.6 hours in survivors (P = 0.04). No other risk or demographic factors correlated with mortality. Despite a known AAA, significant delay in seeking medical advice occurred, and this delay resulted in decreased survival. Patient education is imperative if nonoperative treatment is chosen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793734 TI - Is CT portography (CTAP) really useful in patients with liver tumors who undergo intraoperative ultrasonography (IOUS)? AB - The objectives were to compare the role of CT during arterial portography (CTAP) and intraoperative ultrasound (IOUS) in the management of patients with primary or metastatic liver tumors; to study the ability of CTAP to define resectability before laparotomy in these patients; and to study whether the omission of CTAP in the imaging algorithm resulted in a diminished resectability rate. Eighty-eight consecutive patients with primary or metastatic liver cancer who underwent CTAP and/or IOUS between January 1990 and December 1993 were reviewed. Thirty patients had both CTAP and IOUS and underwent 31 laparotomies (Group I). The sensitivity of these two tests to detect liver tumors was compared. Twenty-eight explorations were performed for hepatic metastases and three for hepatocellular carcinoma. Fifty-three patients, including those in group I, underwent CTAP before laparotomy and were studied to assess the sensitivity of CTAP in determining unresectability (Group II). Thirty-five patients (Group III) had IOUS only and were studied to determine whether the omission of CTAP decreased the resectability rate. In Group I, 52 hepatic lesions were found by a combination of imaging studies, operative exploration, and pathologic examination. The sensitivity of CT, CTAP, IOUS, and exploration were 67 per cent, 65 per cent, 100 per cent, and 75 per cent, respectively. IOUS was more sensitive than any other modality in detecting liver tumors (P < 0.001). It added new information in 7/31 cases (23%). The false positive rate of CTAP was 4/31 (13%). In one case (3%), a false positive result would have precluded a curative resection. CTAP changed management of 4/53 patients (7.5%) by showing unresectable disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793735 TI - The use of tranexamic acid to reduce postoperative bleeding following cardiac surgery: a double-blind randomized trial. AB - Bleeding during the first 24 hours following cardiac surgery using cardio pulmonary bypass (CPB) is a serious complication. Attempts to modify the degree of postoperative bleeding with pharmacologic therapy have met with limited success. Tranexamic acid, a potent inhibitor of plasminogen, may decrease the amount of mediastinal bleeding following surgery utilizing CPB. We assigned 30 patients who were about to undergo cardiac surgery to a double-blind randomized trial. The treatment group received tranexamic acid, given intravenously as 10 mg/kg over 30 minutes, at the time of skin incision, followed by a 1 mg/kg/hr infusion for 12 hours. The control group received a placebo (saline) of equal volume. Measurements of shed mediastinal blood and transfused homologous blood were made at 6, 12, and 24 hours postoperatively. Mediastinal blood loss in the treatment and control groups was 382 mL versus 594 mL at 6 hours (P = 0.08), 502 mL versus 848 mL at 12 hours (P = 0.04), and 711 mL versus 1160 mL at 24 hours (P = 0.02). The mean transfusion volumes after 24 hours were 356 mL in the treatment group and 528 mL in the placebo group (P = NS). Prophylactic tranexamic acid infusion decreases mediastinal blood loss following cardiopulmonary assisted cardiac surgery. PMID- 7793737 TI - Marked asymmetry of LES: important element of LES barrier in subsets of patients with reflux symptoms. AB - Computerized axial manometry (CAM) of the lower esophagus measures squeeze pressure at multiple points in each segment of the lower esophageal sphincter (LES), calculates several unique parameters of LES function, and constructs a 3-D display of the LES. Whether parameters derived from CAM, such as the radial mean pressure (LESrmp), Asymmetry (Asym), and Vector Volume (VV), have relevance to function of the LES remains undefined. This study compares the results of CAM in patients with gastroesophageal reflux disease (GERD) and controls. There were 54 patients with GERD and 21 volunteers; all underwent CAM as part of their evaluation; GERD was defined by clinical and endoscopic examinations, and all patients had abnormal 24-hour pH tests. Statistical evaluation was performed. The LESrmp and the Vector Volume were significantly correlated in both groups of patients and differed significantly in both. Asymmetry of the LES was a significant negative factor in LES strength as shown by VV and LESrmp. Asymmetry alone, however, did not show a strong correlation with reflux. Asymmetry is indirectly correlated with the major determinants of LES strength; in patients with low VV, asymmetry might be a critical factor. When a high VV is present, asymmetry has no particular relevance. CAM provides invaluable measurements of the LES. PMID- 7793736 TI - Preoperative administration of antibodies against tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. AB - This study investigates the effects of preoperative intravenous administration of antibodies against TNF-alpha and IL-1 on peritoneal adhesion formation. Fifty-six Sprague-Dawley rats (350-400 gm) were used in this study. Eight rats were used to empirically determine the amount of anti TNF-alpha and anti IL-1 needed for complete in vivo neutralization. This amount was used for preoperative treatment of selected groups. Forty-eight rats were divided into four equal groups (n = 12). All rats underwent a midline laparotomy. Ten cm square of cecal serosa was abraded, the peritoneal cavity was irrigated with normal saline, and the incision was closed in layers. Cultures were obtained intraoperatively and rats with positive cultures were excluded. Rats in Group 1 were not treated (control), while rats in Groups 2, 3, and 4 were treated with anti TNF-alpha, anti IL-1, and a combination of anti TNF-alpha and IL-1 respectively. All rats were killed at 3 weeks, and peritoneal adhesions were graded using a scale of 0 (none) to 3 (extensive, dense). Rats treated with anti IL-1 (Group 3) and those treated with a combination of anti TNF-alpha and anti IL-1 (Group 4) had significantly fewer adhesions when compared with Group 1 (control) (P < 0.01 and < 0.005, respectively). Least adhesion formation was associated with Group 4 rats. In conclusion, selective immunosuppression, at a molecular level, appears to have a significant impact on rates of postoperative peritoneal adhesion formation. PMID- 7793739 TI - Ileoproctostomy is preferred over ileoanal pull-through in patients with indeterminate colitis. AB - A 15-year retrospective review was undertaken to evaluate the operative outcomes of patients with indeterminate colitis who were referred for rectal-sparing operations. Review of 95 consecutive patients operated for ulcerative colitis (UC) or indeterminate colitis (IC) revealed characteristics of IC in 13 patients. In the group as a whole, there were 45 females and 50 males; the average age was 33. A total of 64 patients had ileoanal pull-through (IAA). Analysis revealed that four of these patients had IC revealed by findings before operation in three patients and following the first stage of operation in one patient. Three of these four patients have subsequently required permanent ileostomy. Six patients who underwent IAA have subsequently demonstrated signs and symptoms of Crohn's disease (CD). All six have subsequently required ileostomy. Overall 10 patients with CD underwent IAA, and nine have required permanent ileostomy. Fourteen patients had ileorectal anastomosis (IRA) for UC or IC. IRA was performed for patients with IC in nine cases, and five patients with UC elected this operative option. Indications for IRA in patients with UC included obesity, 2; mental retardation, 1; advanced age, 1; and patient preference, 1. Of the patients with IC who underwent IRA, two have subsequently shown signs and symptoms of Crohn's disease. Overall, 14 of 14 patients who had IRA still have functioning IRA. None has required ileostomy. The poor results in patients with UC or IC subsequently shown to have CD have caused us to change our operative approach in patients with any question in the diagnosis of UC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793740 TI - Experience with surgical resident training in a combined program in plastic surgery. AB - Healthcare reform may impact graduate medical education (GME) to reduce both specialty training positions and the length of training in these programs. General Surgery residencies often provide prerequisite training for surgery specialty training and will be affected by these changes. The purpose of this study is to identify the quality, outcome, and differences between PGYI-PGYIII categorical general surgery residents (GS) and matched prerequisite plastic surgery residents (PS). Concurrent comparisons analyzed American Board of Surgery Inservice Training Examinations (ABSITE) data from 1980-1992 as well as the surgery operative logs (SOL) and the curriculum of matched residents from 1989 1992. Outcome was assessed by board performance and from a piloted questionnaire to all PS graduates of the combined (3-year GS and 2-year PS) program. ABSITE analysis demonstrated satisfactory performance for both PS and GS at each PGY level, with significant increases each year for GS, but only between PGYI and PGYII for PS; there was a significant difference between PS and GS at all PGY levels. SOL analysis paralleled the curriculum and demonstrated more plastic surgery for PS compared to GS, with no difference in general surgery or hand surgery. PS program graduate respondents (32/44-72.7%) identified that the GS training/PS training was appropriate (71.9%/93.8%), effective (90.7%/93.8%) and of appropriate duration (87.5%/75.1%). 87.5 per cent of PS graduates completed ABPS certification. Combined PS training in all PS programs would reduce GME payments by over $20 million. Combined PS training is effective, appropriate, resource-efficient, and has an excellent outcome, but it requires a specific curriculum and close coordination between General Surgery and Plastic Surgery programs. PMID- 7793738 TI - Reconstruction with myocutaneous flaps following resection of locally recurrent rectal cancer. AB - Local or regional recurrence is frequent in patients treated for rectal cancer. Many will die with regional disease in the absence of distant metastases. To achieve cure or palliation, radical surgery resulting in large pelvic defects may be warranted. Myocutaneous flap reconstruction may be used to achieve satisfactory closure. From 1988 to 1993, nine patients (5 female, 4 male) underwent 10 myocutaneous flap reconstructions for large perineal or pelvic defects following surgical extirpation of recurrent rectal cancer at Fox Chase Cancer Center. All nine patients had been previously treated with radiation therapy. Their clinical course was reviewed and quality of life assessed. The mean age at diagnosis of recurrence was 56 years. In six, this was a first, and in three patients a second recurrence. Clinical presentation was most often bleeding, abscess, or perineal pain. Resection was determined by extent of recurrence and included perineal resection, pelvic exenteration, cystectomy, sacrectomy, or coccygectomy. Extent of disease necessitated intraoperative radiation therapy in one case and placement of brachytherapy catheters in four. Bilateral gracilis flaps were used in four, unilateral in three, gluteus maximus in two, and combined gluteal and gracilis flaps in one patient. Six perineal and four combined perineal and vaginal defects were reconstructed. The mean length of surgery was 9.1 hours, and the length of hospitalization averaged 17.5 days. In nine of 10 cases, patients had prehospital level of function at discharge. Acute surgical flap-related complications included three cases of minor wound infection or separation, two of minimal but persistent drainage, and one of vaginal colonization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793741 TI - Laparoscopic liver biopsy in patients with coagulopathy, portal hypertension, and ascites. AB - The safety, reliability, and technique of laparoscopic liver biopsy were evaluated in 22 consecutive patients with coagulation abnormalities who were considered high risk for standard percutaneous liver biopsy. Fifty-eight biopsies were performed in 15 men and seven women. All patients had a prolonged prothrombin time (> 13.5 seconds), bleeding time (> 9 minutes), or thrombocytopenia (< 100,000 TH/UL). Ten patients (45%) had more pronounced coagulation abnormalities defined as a prolonged PT > 2.5 seconds or < or = 30% control, platelet count < 50,000 TH/UL, or bleeding time twice normal. Thirteen patients (59%) had both thrombocytopenia and a prolonged PT. Ascites was present in 19 patients (86%) and portal hypertension in 16 (73%). Laparoscopic liver biopsy was performed under general anesthesia, most commonly using two trocar sites and an open laparoscopic technique. Hemostasis was most effectively obtained by application of direct pressure and topical gelfoam and thrombin. A postoperative drop in hemoglobin of > or = 1 gm per cent occurred in four patients. One patient required laparotomy for postoperative bleeding and was the only patient requiring transfusion of red blood cells. Other complications included two minor ascitic leaks, one small subcapsular hematoma, and one wound infection. In conclusion, laparoscopic liver biopsy can be performed safely and reliably in patients with conditions contraindicating percutaneous biopsy. PMID- 7793742 TI - Recent experience with cancer of the ampulla of Vater in a national hospital group. AB - A total of 64 resections, 24 operative bypasses and 35 nonoperative biliary intubations, were performed for ampullary carcinoma in U.S. Dept. of Veterans Affairs hospitals from 1987 to 1991. Mean survival after resection was 702 days, significantly higher (ANOVA, P < or = 0.005) than that after bypass (345 days) or intubation (385 days). Operative mortality rates were similar: resection or intubation = 14%, bypass = 12%. Operative (30-day) mortality was zero in four local resections, 10% in 51 Whipples and 44% in nine total pancreatectomies. TNM staging was available for 74 patients, and mean survival after resection exceeded 2 years in 34 patients with Stage I-II (localized) cancers, was 532 days in 10 patients with Stage III (regional nodes +) and 77 days in two patients with Stage IV (metastatic) disease. However, mean survival without resection was 498 days in 14 patients with localized cancer, 634 days in two patients with regional and 215 days in 11 patients with distant metastases. Resection clearly increased survival only for Stage I cancers (P < or = 0.02). Predicted 5-year survival rates by stage after resection were: I-II = 21%, III < 10%, IV = 0%. Complications were recorded in 29 per cent of resected patients, with sepsis the most common (21% of resections). Both sepsis and GI bleeding significantly decreased mean survival (P < or = 0.05, ANOVA), but pneumonia, pancreatic fistula, or wound problems did not. Ampullary cancer is a favorable subtype of peri-ampullary cancers, but prolonged survival is also seen without resection and may be largely limited to tumors that do not involve regional nodes. PMID- 7793744 TI - Surgical office-based ultrasound of the breast. AB - How surgical office-based ultrasound (US) influences the management of nonpalpable, new or increasing size, mammogram-detected breast masses was evaluated. Ninety-seven patients had diagnostic US only; of these, 67 had their mass diagnosed as a simple cyst, and 30 had a negative US. Fifty-three additional patients underwent US-guided aspiration and/or biopsy (US-GAB) of their breast mass after diagnostic US. Of 12 patients with diagnostic US of "simple cyst," US GAB confirmed each to be cysts. Of five patients with diagnostic US of "fibroadenoma," four had fibroadenomas and one had insufficient tissue on US-GAB. In all five cases a fibroadenoma was diagnosed at open biopsy. Of 27 patients with diagnostic US of "indeterminate" (cyst versus solid/complex cyst), 15 had cysts, one had a fibroadenoma, and one had a papilloma on US-GAB; the latter two were confirmed on open biopsy. Ten of these 27 patients had fibrocystic change identified on US-GAB; six were benign on open biopsy, and four had no change on follow-up mammogram. Of nine patients with diagnostic US of "suspicious," three had carcinomas, five had fibrocystic change, and one had insufficient tissue on US-GAB; three cancers were confirmed, and the remaining six were benign on open biopsy. There were no false positives and no false negatives among those patients undergoing US-GAB. In conclusion, office-based ultrasound of the breast performed by surgeons can accurately diagnose nonpalpable simple cysts and can accurately guide needle aspiration and/or biopsy of probable fibroadenomas, indeterminate, or suspicious masses for diagnosis of cystic, benign solid, or malignant lesions. PMID- 7793743 TI - Closed drainage versus open packing of infected pancreatic necrosis. AB - Infected pancreatic necrosis is the most lethal form of pancreatic infections. We have compared our results of open packing and closed catheter drainage after surgical debridement in 20 patients between 1978 and 1993. There were 18 men and 2 women, ages 18 to 72 (mean 54 years). Pancreatitis was attributed to alcohol in eight patients, gallstones in four, surgery in four, hyperlipidemia in one, and was unknown in one. The most common infectious organisms were Strep. viridans, E. coli, Staph aureus, and Candida albicans. Surgical debridement and closed catheter drainage without lavage was the initial treatment in nine patients. Seven of 9 (78%) required reoperation for recurrent abscess and necrosis. Procedure related morbidity was 70 per cent and overall mortality was 44 per cent. Sepsis was the cause of death in three patients and multi-system organ failure in one patient. Surgical debridement and open packing was performed in 11 patients. Each patient had scheduled reoperations for repeat debridement and packing an average of 10 times over 21 days. Procedure-related morbidity was 73 per cent and overall mortality was 18 per cent. One patient died of cardiac failure and one of multisystem organ failure. Retroperitoneal hemorrhage and recurrent abscesses were more frequent after closed drainage, whereas gastric fistula and incisional hernia were more frequent after open packing. Ventilator dependence, pancreatic and intestinal fistula, and organ failure occurred at the same rate. In conclusion, surgical debridement and open packing, with planned redebridement and packing, is more effective in controlling the septic process than is closed catheter drainage of infected pancreatic necrosis. PMID- 7793746 TI - Congenital thyroid hemiagenesis. AB - Failure of embryologic development of a lobe of the thyroid gland is a rare anomaly. In order to characterize this unusual entity, we report our experience in seven patients with thyroid hemiagenesis involving the left lobe in five and the right lobe in two patients. The diagnosis was made as a result of evaluation and treatment of a thyroid nodule (4), diffuse thyroid enlargement with thyrotoxicosis (2), and a simple goiter in a patient with a prior history of radiation treatment for facial acne. In five patients thyroid scintigraphy demonstrated unilateral absence of function, four of whom had an ultrasound exam of the neck that revealed a corresponding absence of thyroid tissue. In one patient the diagnosis was made incidentally on a screening ultrasound exam of the neck. Thyroid hemiagenesis was unsuspected preoperatively in one patient with Graves' disease because of marked hyperplasia of a single thyroid lobe and isthmus. Thyroid hemiagenesis was confirmed in four patients who underwent thyroidectomy. The presence of a thyroid isthmus was established in six patients. Postoperatively, all patients were treated with thyroid hormone. Associated thyroid pathology included adenoma (1), follicular carcinoma (1), colloid nodule (2), Graves' disease (2), and a simple goiter (1). In conclusion, the diagnosis of thyroid hemiagenesis should be considered in any patient with unilateral absence of function on thyroid scintigraphy and confirmed by ultrasonography. Recognition of this rare congenital anomaly is important to avoid unnecessary contralateral neck exploration with its potential morbidity and to insure that all patients receive careful follow-up and appropriate thyroid hormone therapy when necessary. PMID- 7793747 TI - Computational simulation of worker exposure using a particle trajectory method. AB - The velocity field downstream of a worker is approximated with a discrete vortex algorithm. This information is used to calculate trajectories of massless tracer 'particles' released from a point-source of contaminant. Concentrations in the plane of this source are estimated by averaging over a number of such trajectories. Approximations include: (1) representing the worker by a two dimensional elliptical cylinder; and (2) representing tracer gas contaminant by massless particles generated without momentum. These particles are transported by both vortex shedding and turbulent diffusion. Computer-predicted mean concentrations in the near-wake region downstream of the worker compare well with results from wind-tunnel tracer gas experiments employing a mannequin. Subsequently, the concept of a computational breathing zone is introduced, and predictions of worker exposure are made. These simulations of time-integrated breathing zone concentration also compare well with measured values. PMID- 7793745 TI - Simultaneous fine-needle aspiration and core-needle biopsy of thyroid nodules. AB - To evaluate the efficacy of simultaneous fine-needle aspiration (FNA) and core needle (CN) biopsies of thyroid nodules, the clinical course and operative findings in 100 patients having both tests were reviewed. Each patient had a diagnosis made with this approach. Both specimens were adequate for diagnosis in 95 patients. In the remaining 5 patients, a diagnosis was provided by FNA in four and CN biopsy in one. FNA and CN biopsies gave the same diagnosis of either a benign nodule in 53 patients or neoplasia in 30 patients. When both FNA and CN biopsies showed a benign nodule, a nonoperative approach was taken in 43 of the 53 patients. Forty-two patients were operated on either because of biopsy findings (32) or clinical indications (10). The surgical specimens were used to determine the false positive and false negative rates, the sensitivity, specificity, and accuracy for the diagnosis of neoplasia. The false (+) and false (-) rates in diagnosing neoplasia were 33 per cent and 7 per cent for FNA, 20 per cent and 4 per cent for CN biopsy, and 20 per cent and 0 per cent for both. The sensitivity, specificity, and accuracy for FNA were 93 per cent, 67 per cent, and 83 per cent, for CN biopsy 96 per cent, 80 per cent, and 90 per cent, and 100 per cent, 80 per cent, and 93 per cent for both FNA and CN. All neoplasms were detected, and no thyroid carcinomas were missed by this combination. There was only one complication: bleeding after a CN biopsy. Combined FNA and CN biopsies allow most patients with thyroid nodules to avoid an unnecessary operation and accurately diagnose those with thyroid carcinoma. These two procedures are safe and complementary. PMID- 7793748 TI - Correlation between different measures of exposure in a cohort of bakery workers and flour millers. AB - This paper describes the relationship between continuous and 'grouped' variables for several measures of exposure in a longitudinal study of bakery workers and flour millers. Average shift and peak levels, both for dust and for flour aeroallergen were measured, duration of exposure obtained from questionnaire and cumulative exposure both for dust and for flour aeroallergen calculated. Neither for dust nor for flour aeroallergen was there a correlation between duration of exposure and intensity measures of exposure (peak and average). Moderate to good correlation existed between the various intensity measures of exposures both for dust and for flour aeroallergen. Good correlations existed between measures of exposure of dust and measures of exposure for flour aeroallergen. The degree of correlation was reflected by the fact that the number of workers changing categories depended on which measure of exposure was considered. The higher the correlation coefficient between various measures of exposure the fewer workers changed category. This information provides important information for a better understanding of the exposure-response relationship amongst bakery workers and flour millers. PMID- 7793749 TI - Flour dust exposure variability in flour mills and bakeries. AB - As part of a longitudinal study to explore the exposure-response relationship between flour dust exposure and work-related symptoms and skin sensitivity the authors formed exposure groups and estimated various components of variability. This paper describes the between-exposure group, the between-worker and the within-worker variation of personal flour dust exposure in bakeries, flour mills and packing stations. In total 346 samples were collected in 13 exposure groups. The geometric means of the exposure groups ranged from 0.3 up to 9.0 mg m-3. Between-worker variances within exposure groupings were less than the overall between-worker component although substantial differences in exposure between workers remained in some exposure groups. Overall the largest variance component was the between-exposure group component followed by the considerably smaller between-worker and within-worker components. PMID- 7793750 TI - Epidemiological study of eye irritation by hydrogen sulphide and/or carbon disulphide exposure in viscose rayon workers. AB - In the framework of an extensive health survey 123 male viscose rayon workers exposed to hydrogen sulphide (H2S) and/or carbon disulphide (CS2) and 67 referents not exposed to either of these chemicals answered questions on eye irritation complaints in a self-administered questionnaire. Personal exposure varied from 4 to 112 mg m-3 for CS2 and from 0.2 to 8.9 mg m-3 for H2S. A combined exposure measure was calculated using principal component analysis. The exposed subjects had a significantly higher prevalence of eye pain, burning and photophobia. Adjustment for age and smoking in logistic regression revealed significantly more eye complaints for all workers that were highly exposed. In a postal survey one-third of the ex-workers of the same viscose rayon factory reported having left the factory because of eye complaints, indicating that their occurrence may be underestimated in the cross-sectional study. PMID- 7793751 TI - Particle inhalability curves for humans and small laboratory animals. AB - Several inhalability curves for nose breathing in humans have been developed. No studies have been designed specifically to develop inhalability functions for animals, although it has been shown that pulmonary deposition of large particles (> 4-5 microns) via inhalation is minimal in laboratory animals [Raabe et al., Inhaled Particles VI, pp. 53-63. Pergamon Press, Oxford (1988)]. The logistic function was fitted to these animal deposition data of Raabe et al. (1988) to estimate an inhalability curve for laboratory animals. The logistic function was also fitted to the human data of Breysse and Swift [Aerosol Sci. Technol. 13, 459 464 (1990)] for comparison. The results suggest that ambient concentration is a good predictor (inhalability > 95%) of inhaled concentration for humans for particles < 11 microns dae. In small laboratory animals, however, the inhalable portion of the ambient concentration is predicted to be 95% for 0.7 microns dae particles but declines to 45% for 10 microns dae particles. It is, therefore, important to consider the effects of inhalability when estimating dose delivered to the target tissue in animals. In comparing delivered doses between animals and humans, adjusting for inhalability may change not only the magnitude of the difference but also which species is predicted to receive a greater delivered dose. PMID- 7793752 TI - Polycyclic aromatic hydrocarbon exposure in coal liquefaction workers: the value of urinary 1-hydroxypyrene excretion in the development of occupational hygiene control strategies. AB - Studies in coal liquefaction workers were conducted to examine relationships between work activities, exposure to polycyclic aromatic hydrocarbons (PAHs) and excretion of urinary 1-hydroxypyrene (1-OHP). In a single-week study in operators, the end of work period 1-OHP excretion was an order of magnitude higher than in a shadow control subject, who experienced exposure by inhalation only (shadowed operator = 15.8 mumol mol-1 creatinine; shadow control = 1.07 mumol mol-1 creatinine). Dermal exposure was estimated to account for over 70% of excreted 1-OHP in exposed workers. A second study over 4 consecutive weeks (multi week study) showed consistency in 1-OHP excretion from week to week both in operators and laboratory technicians, indicating little variation in weekly exposures for these workers. Excretion levels in maintenance workers however, showed some week to week variation, consistent with the variable nature of exposures associated with this type of work. A further study involving an end of work period spot assessment for all personnel showed a clear distinction between exposed workers (operators and maintenance staff) and other workers not thought to be exposed (laboratory technicians and office staff). Findings in the course of these studies indicated that there is no loss of 1-OHP at 4 degrees C, compared with -20 degrees C. On the basis of work to date at the coal liquefaction facility, hygiene control strategies have been proposed involving periodic urinary 1-OHP monitoring. PMID- 7793753 TI - Exposure of the deck crew to carcinogenic agents on oil product tankers. AB - Work on deck on eight oil product tankers was examined. The purpose was to evaluate the need for improvement of the working environment to reduce the risk of occupational cancer. Benzene, polyaromatic hydrocarbons (PAHs) and organic lead compounds were sampled, and the crew answered a questionnaire on acute health effects. By area monitoring, benzene was generally found to be in the range from the detection limit, of 0.01 ppm, up to 1.15 ppm, but one tanker which loaded gasoline with the hatches open had levels up to 55 ppm. Personal monitoring showed exposure levels in the range 0.01-1.15 ppm. The PAH-levels and the levels of organic lead were low. No seamen were observed using respiratory protective equipment. Central nervous system symptoms were reported by the crew with the highest exposures to benzene although benzene may not be the only cause. The exposure to benzene and other hydrocarbons on the deck of oil product tankers ought to be reduced. PMID- 7793754 TI - Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content. AB - Among 441 cases of malignant mesothelioma in the author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 +/- 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 microns or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy (P < 0.05). Individuals with direct exposures had on average higher asbestos contents than patients with indirect exposures. Furthermore, for each duration of exposure, shipyard workers had on average higher asbestos contents than non-shipyard workers (P < 0.05). Mesotheliomas are associated with a wide range of durations of exposure to asbestos and pulmonary asbestos burdens, and there is a rough correlation between duration of exposure and pulmonary commercial amphibole content. PMID- 7793755 TI - Biologically relevant assessment of dermal exposure. AB - Dermal uptake of hazardous substances is dependent on the concentration of the material on the surface of the skin rather than its mass. It is suggested that it would be appropriate to consider the integral of concentration, over the skin surface and throughout the exposure duration, as an appropriate index of dermal exposure. For a low volatility substance this exposure index would correspond to the product of concentration, area of skin exposed and the duration of exposure. For volatile materials the magnitude of the exposure index would additionally depend on the loss of the substance by evaporation. This dermal exposure index is more likely to reflect the contribution to the overall dose received from the skin than the previously used determinations of mass of hazardous substance on the skin. Suggestions are made for possible methods of making measurements using this index. PMID- 7793756 TI - [Towards a 1st French consensus development conference on a dermatologic topic]. PMID- 7793757 TI - [Hair dysplasia in oculo-dento-digital syndrome. Apropos of a mother-daughter case]. AB - Oculo-dento-digital syndrome (SODD) as defined by Meyer-Schwickerath in 1957 is a rare entity (84 cases) which belongs to ectodermal dysplasias. It consists of: the characteristic features (long face, pinched nose); syndactyly; ocular, dental and bone abnormalities. This entity is usually transmitted on the autosomal dominant mode. We report two cases (a mother and daughter) with polymalformations which we classed as SODD. Furthermore, agenesis of lacrimal duct and genitourinary abnormalities were noted. The mother had a very particular complex hair shaft dysplasia (incomplete pili torti, "tiger tail" aspect, fractures) with alopecia since she was fifteen years old. The daughter's hair was normal at birth. In SODD, fine and sparse hair is often observed (44 p. 100). Only one patient had hair shaft investigation under polarized light: pili annulati and monilethrix were described but not found in our cases. These two reports incite to the systematic hair shaft study in SODD as other ectodermal dysplasia syndromes. PMID- 7793758 TI - [Focusing on a test to evaluate the efficacy of skin barrier creams]. AB - INTRODUCTION: The aim of this study was to adjust an experimental protocol with the rabbit to control the skin barrier creams efficacy. ELABORATE TECHNIQUE: Therefore, we applied irritant aqueous solutions and solvents on the shaved skin of the rabbit flank protected with one of these creams. We noticed inflammatory reactions of erythema and oedema but we also conducted an histological examination of the treated skin. DISCUSSION: This protocol is simple, there is no investment with equipment and only a few number of rabbits are required. There is only a difficulty with applying the same volume of cream since cream consistency is variable and makes the comparison between the different creams quite delicate. This method should be supported by well-controlled studies between several laboratories. PMID- 7793760 TI - [Parry-Romberg syndrome associated with homolateral segmental vitiligo]. AB - We report the case of a 11 year-old girl with segmentary vitiligo in the left side of the neck and superior part of the hemithorax, associated to an homolateral Parry-Romberg syndrome. This association had never been reported. The pathogenic hypothesis are discussed. We think that this association can be explained by the autoimmune origin of these diseases. PMID- 7793759 TI - [Adult T-cell leukemia associated with HTLV-1 in a HIV-2 seropositive African]. AB - INTRODUCTION: The aim of this report is to describe an HIV-2 seropositive patient from Mali who had adult-T cell Leukaemia/Lymphoma associated with HTLV-I infection. CASE REPORT: The patient presented with erythroderma and foliate lymphocyte leukaemia. Skin biopsy showed an epidermotropic lymphoma. Tumoural cells expressed a mature T-cell phenotype CD4+/CD25+. High anti-HTLV-I titers and the evidence of monoclonal integration of HTLV-I provirus within circulating lymphoid cells led to the confirmation of HTLV-I as the causal agent in tumour cell transformation. HIV-2 serology was positive. DISCUSSION: Sub-Saharan Africa is a vast reservoir of HTLV-I virus with at least 5 million infected persons. Cases of adult-T cell Leukaemia/Lymphoma in Africans are exceptional. Lack of sufficient knowledge of the disease could partially explain this discrepancy. The main differential diagnosis in dermatology is primary T-cell lymphomas of the skin, particularly mycosis fungoides and Sezary syndrome. PMID- 7793761 TI - [Unilateral isolated purpura disclosing scurvy]. AB - We report a case of scurvy. This case is interesting by the unilateral character of the ecchymotic leg's purpura. Ascorbic acid assays do not yet enable subclinical vitamin C deficiency to be reliably detected. Hence the importance of knowing the situation which expose to this deficiency. PMID- 7793764 TI - [Vulvar involvement in Crohn disease]. AB - INTRODUCTION: There are many skin manifestations of Crohn's disease including specific lesions occurring late after digestive signs. These manifestations are also termed metastatic and are rarely located on the vulva. CASE REPORT: We observed a metastatic localization in the vulva of Crohn's disease in a 34-year old woman with predominantly rectosigmoid disease. The right labia major was greatly enlarged with oedema involving the inguinal cural area. Pustulization and erosive lesions were seen. The course of these lesions was independent of the colonic disease and responded temporarily only to a triple drug combination of metronidazol, prednisolone and minocyclin. CONCLUSION: This case emphasizes the frequency of colonic or rectal manifestations associated with vulval involvement in Crohn's disease. The metastatic lesions follow a course independent of the digestive disease raising therapeutic problems in this localization. PMID- 7793762 TI - [Buschke-Ollendorff syndrome]. AB - The Buschke-Ollendorff syndrome (BOS) is a rare connective tissue disorder inherited in an autosomal dominant pattern characterized by cutaneous lesions, dermatofibrosis lenticularis disseminata, and osteopoikilosis. We report a new case of this syndrome in a 66 year old man, interesting by its association with a protein C deficiency, another rare genetically transmitted disease. Diagnosis of the BOS is difficult on the mere cutaneous lesions; it is therefore important to systematically practice bone X-rays in the presence of atypical pseudoxanthoma elasticum, disseminated collagenoma or disseminated connective tissue or elastic nevi. The radiologically detectable osteopoikilotic bone lesions, evoking Paget's disease, easily sign the diagnosis. In our case, the association of a protein C deficiency with the BOS may not be fortuitous because both the elastin and protein C genes are localized on chromosome 2q. PMID- 7793766 TI - [Keratoacanthoma centrifugum marginatum]. AB - INTRODUCTION: Keratoacanthoma centrifugum marginatum (KCM) is a rare keratoacanthoma. Treatment relies essentially on exeresis which is however difficult due to the widespread nature of the lesions. CASE REPORT: A patient with a 1 year history of KCM associated with psoriasis vulgaris was successfully treated with etretinate (1 mg/kg/day) for 5 months. This medical therapy made it possible to avoid the classical surgery and to blanch the associated psoriasis. COMMENTS: Several authors have shown the favourable effect of etretinate on multiple or large single-site keratoacanthomas. To our knowledge, this is the first case reported of successful treatment with etretinate in a case of keratoacanthoma associated with psoriasis. We suggest that this drug could be an effective alternative to mutilating surgery for this specific variety of keratoacanthoma. PMID- 7793765 TI - [Lymphomatoid papulosis and anaplastic giant-cell lymphoma]. AB - INTRODUCTION: The association between lymphomatoid papulosis and malignant Hodgkin or non-Hodgkin lymphoma is well known but still raises the problem of nosology between these two pathologies. Is lymphomatoid papulosis a pseudolymphoma, a prelymphomatous state or a true skin lymphoma? CASE REPORT: We observed a patient who had lymphomatoid papulosis and anaplastic large-cell lymphoma within an interval of 8 years between. This case was particularly interesting because identical immunophenotypes were observed in the atypical large-cells of the skin and the lymphomatous cells of the lymph nodes (positive for CD43, CD45, CD25, CD30, CD15, EMA). DISCUSSION: This case points out that atypical large-cells of lymphomatoid papulosis express the CD15 antigen which is only expressed by atypical large-cells in half of the cases of lymphomatoid papulosis. In addition, EMA is classically expressed in primary lymph node lymphomas rather than in primary cutaneous anaplastic large cell lymphomas which could predict extracutaneous dissemination of lymphomatoid papulosis. Furthermore, the demonstration that the skin lesions and the lymph nodes responded differently to the same treatment would suggest that there are other unrecognized biological differences. Lymphomatoid papulosis appears to be a range of disorders of the lymphoproliferation of activated T-cells and could include varioliform parapsoriasis and cutaneous lymphoma. PMID- 7793763 TI - [A case of unilateral elastosis with cysts and comedones. Favre-Racouchot syndrome]. AB - INTRODUCTION: Cutaneous elastosis with cysts and comedones (Favre-Racouchot) is one of the oldest known manifestations of helioderma. Both sides of the face are usually involved symmetrically. CASE REPORT: We observed a 65-year-old woman with extremely severe Favre-Racouchot disease localized exclusively on the left side of the face. The diagnosis of elastosis with cysts and comedones was confirmed histologically. This elastosis with cysts and comedones was associated with spasms of the hemiface treated with injections of botulinic toxin. This association was fortuitous and we retained actinic irradiation as the causal agent in this woman who had worked for 15 years in the same room. The elastosis occurred on the side of the face which had been continuously exposed at the same orientation to the window. COMMENTS: This original observation is similar to cases where facial exposure to artificial light or sunlight is asymmetrical, leading to a higher incidence of lesions on one side of the face: colloid milium, actinic keratosis, Dubreuilh melanoma (malignant lentigo) or simple helioderma. The asymmetrical nature of the actinic lesions is often related to automobile driving. This case was particular since it demonstrated that Favre-Racouchot elastosis with cysts and comedones is due to actinic irradiation and not to skin aging. PMID- 7793768 TI - [Is ischemic ulcer of the leg a good model for pharmacoclinical experiments?]. PMID- 7793767 TI - [Treatment of Langerhans-cell histiocytosis by oral cyclosporin A and topical nitrogen mustard]. PMID- 7793770 TI - [Grover disease and gastric adenocarcinoma]. PMID- 7793769 TI - [Hirsutism treated by estrogens and anti-estrogens: disclosure of porphyria cutanea tarda. Association with chronic hepatitis C]. PMID- 7793771 TI - [A case for diagnosis: Osler's nodes and Janeway lesions]. PMID- 7793773 TI - [Superficial thrombophlebitis]. PMID- 7793774 TI - [Management of deep venous thrombosis of the lower limbs]. PMID- 7793775 TI - [Surgery of arterial ulcers]. PMID- 7793776 TI - [Monthly question: antihistaminics and pregnancy]. PMID- 7793772 TI - [A case for diagnosis: phlegmasia cerulea dolens]. PMID- 7793778 TI - Measurement of breast implant volume with magnetic resonance imaging. AB - In principle, tomographic imaging of breast implants provides the information needed to compute implant volume. We have investigated the reliability of this measurement as a means of diagnosing the loss of gel from the implant. We find that measurement errors, postimplantation changes of the implant, uncertainties in the patients' records, and lack of knowledge of the implant temperature in the body can lead to significant discrepancies, making this measurement unreliable as a diagnostic tool. PMID- 7793777 TI - Do patients with silicone-gel breast implants have elevated levels of blood silicon compared with control patients? AB - Whole blood silicon levels in 30 patients with silicon-gel implants (inserted between 1973 and 1991) were compared with those of 24 healthy, age-matched, female patients without breast implants using atomic absorption spectrometry with a graphite furnace. The blood silicon levels in the implant patients were significantly higher than those of controls (medians 33.45 vs 17.05 ng/ml; p = 0.005). Of the 30 patients with implants, 15 had received their implants between 1973 and 1985, and 15 had received implants between 1986 and 1991. Implants made between 1973 and 1985 have been shown to be weaker and to have higher silicone "bleed" levels than those made from 1986 onward. However, there were no significant differences in the blood silicone levels between these two groups of patients. PMID- 7793779 TI - Utility of magnetic resonance imaging and ultrasonography in diagnosing breast implant rupture. AB - We prospectively evaluated 81 patients (with 160 implants) who subsequently had implants removed to determine sensitivity and specificity of both magnetic resonance imaging and ultrasonography. Positive and negative predictive values were also calculated to determine whether a statistically beneficial interaction existed when ultrasonography and magnetic resonance imaging were used in combination to examine an implant. Finally, the misdiagnoses were retrospectively evaluated to identify the pitfalls of the investigations. Positive diagnostic criteria were described. The sensitivity and specificity of ultrasonography were 47% and 83%, respectively, and of MRI, 46% and 88%, respectively. On retrospective review by the radiologist, the sensitivity and specificity of ultrasonography were 70% and 90%, respectively, and of magnetic resonance imaging, 75.6% and 94%, respectively. Although definite conclusions could not be obtained, there did not seem to be an additive benefit from using both ultrasonography and magnetic resonance imaging. PMID- 7793780 TI - Anthropometric optical surface imaging system repeatability, precision, and validation. AB - Disciplines using human body surface dimensions require accurate, repeatable measurements. This study presents a design for the analysis of repeatability, precision, and validation of a new anthropometric device. This model enables estimation of the proportion of the total variation attributable to each level of data collection. This model is applied to an analysis of repeatability, precision, and validation of the Cencit Imaging System, a new optical surface scanner. Twenty-seven facial landmarks were marked on 10 men and 10 women at two measurement sessions. Two images were scanned during each session, and each image was digitized twice. The Cencit Imaging System results were compared with a previously validated digitizer. The Cencit Imaging System was found to produce accurate, highly repeatable images. Much of the error in this study is attributable to human error in marking landmarks on the subjects. The new imaging system will prove useful in a variety of anthropometric applications. PMID- 7793781 TI - Functional and social long-term results after free tissue transfer to the lower extremity. AB - We report the long-term social and functional results in 53 patients receiving free tissue transfer after trauma to the lower extremity. The results are compared with those of a matched group of patients receiving primary amputation. The microsurgically treated patients had significantly more complaints over pain during walk (p = 0.02) and edema (p < 0.00005). Regarding social results, no significant differences between the two groups were found. Time until surgery, infection, or bone defect before free flap surgery did not alter the overall results significantly. It is concluded that the long-term functional and social results after free tissue transfer are almost the same as those achieved after simple amputation. Because the median time until free flap surgery in this series was 158 days, early limb-saving procedures could possibly improve the long-term results. PMID- 7793782 TI - Using the split Latram for better breast projection in breast reconstruction. AB - Over the years, although methods of breast reconstruction have improved, the ability to build a symmetrical projecting breast has not. When stacked Meme implants were used, better projection was obtained. Folding the transverse rectus abdominis musculocutaneous flaps allows for good projection; however, the breast is then quite wide and large. For smaller breast women with projection and some larger breasted women as well, splitting and stacked flaps give a much better result. We now do this procedure with simultaneous Latram and mastectomy surgery in fewer than 3 hours. PMID- 7793783 TI - Minimal expansion for correction of male pattern baldness. AB - Tissue expansion for correction of male pattern baldness has not gained wide acceptance by patients or surgeons because of the substantial albeit temporary deformity of the expansion. Minimal expansion is an alternative. Scalp flaps can be expanded just to the point of becoming noticeable over 4 to 6 weeks followed by scalp flap transposition and easy closure of the donor site. The temporoparietal (Juri) or superiorly based (Dardour) flaps have been used unilaterally or bilaterally. The entire restoration is completed in approximately 8 weeks, is minimally deforming during the expansion phase, and does not require the patient to alter his lifestyle significantly or to go into hiding. Hair grafts, in contrast, do not begin to grow hair until 12 weeks after transplantation, and the process usually requires four sessions over an 8- to 12 month period with the patient looking temporarily variably absurd. Tissue expansion increases scalp available for flap restorations, which appear more natural than even the most well-executed hair transplants. Minimal expansion makes the process more palatable to the patient and surgeon. PMID- 7793784 TI - The Mercedes incision in hair restoration. AB - Standard technique for hair transplantation includes plug composite grafts placed in circular recipient defects of smaller diameter. The plugs can also be placed in slit incisions that are temporarily dilated to accommodate grafts. Two drawbacks of these techniques are the appearance of row cropping resulting from the regular pattern and compression of individual grafts caused by scar contracture. These drawbacks result in tufting and a "doll's head" appearance. The expansile Mercedes incision as described here camouflages these failings. Donor minigrafts are taken with a biopsy punch knife or as strips in a standard fashion. A Mercedes logo-shaped defect is then made at the recipient site using a no. 11 scalpel to create a three-armed stellate incision. The incisions are rapidly made with the axis oriented parallel to the direction of the native hair shafts. The graft is then pushed in flush with the skin. The triangulation eliminates compression of grafts because they are spread in three directions rather than squeezing in a tight circular or slit configuration. The use of the stellate incision along with altering its rotational orientation in a haphazard pattern also prevents row cropping. Thus, the Mercedes incision is quicker and yields an overall improved result. PMID- 7793786 TI - Cutaneous foot malignancies: outcome and options for reconstruction. AB - We retrospectively reviewed 26 cases of primary or recurrent cutaneous foot malignancies for which patients underwent tumor extirpation and reconstructive surgery between 1990 and 1994. The most common disease was malignant melanoma (24 cases), and most tumors were located on the heel and midplantar area. Free tissue transfer was used for nine reconstructions, and various types of plantar, rotation flaps, or split-thickness skin grafts were also used. Twenty-five patients were ambulatory postoperatively without the use of corrective shoes or supportive devices. Sensation was noted to be normal in 20 patients, decreased in 4, and increased in 1. Two free tissue transfers were lost in the same patient because of venous thrombosis. Other complications included partial flap loss, skin graft loss, and flap dehiscence. Several patients have resumed pretreatment running regimens. Cutaneous tumor extirpation followed by reconstructive surgery of the foot does not inhibit the cancer patient's ability to function normally. PMID- 7793785 TI - Free radical damage in acute nerve compression. AB - Nerve compression causes injury by local ischemia and direct mechanical distortion. Peripheral nerves in diabetes mellitus are more prone to injury than those of nondiabetics. We sought to determine whether reperfusion-induced, oxygen derived free radical injury occurs in peripheral nerves subjected to acute compression in normal and chronically diabetic rats. Female Sprague-Dawley rats weighing 250 to 275 g (N = 347) were divided into two groups: normal and streptozocin-induced diabetics. A total of 187 normal and 160 diabetic nerves were analyzed. After 8 weeks of untreated hyperglycemia, the sciatic nerves of normal and diabetes mellitus rats were subjected to one of three operations: a sham operation, 24-hour compression alone, and 24-hour compression followed by 1 hour reperfusion (CR). Nerve compression was established by banding the right sciatic nerve with a Silastic tubing, 1 cm long and 0.62 mm internal diameter, which was secured with 6-0 nylon suture. In the CR group, after 24 hours of compression, the tubings were released for 1 hour to permit reperfusion. Nerve tissue within the zone of compression underwent biopsy examination and was frozen for subsequent analysis. Blood flow to the nerve was quantified by injecting fluorescein (10 mg/kg intravenously) 10 minutes before harvest and measuring tissue levels fluorometrically. Compression with the Silastic tubing significantly reduced neural blood flow by 75%. Blood flow improved but failed to return to baseline levels after tubing release in diabetes mellitus nerves while perfusion returned to baseline in non-diabetes mellitus nerves. Nerve homogenate was assayed for malonyldialdehyde, an indicator of lipoperoxidation, as well as enzymes of cellular defense and glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793787 TI - Triangular flap repair of the congenital earlobe cleft. AB - Repair of a congenital earlobe cleft was performed on 16 patients using a new surgical technique derived from the Tennison-Randall triangular flap operation for cheiloplasty. There were no complications. This method was applied because the deformities and desired outcomes in the congenital earlobe cleft are similar to those of the cleft lip. Many papers have described surgery for congenital and acquired clefts; the former differs from the latter in some respects. The techniques described for the repair of acquired clefts are not always appropriate for congenital clefts. In addition, some operations specifically designed for congenital clefts require more complicated techniques. Using our technique to correct lobule deformities with a triangular flap in proportion to the angle and extent of the cleft, a superior cosmetic result was obtained in the repair of longitudinal earlobe clefts. PMID- 7793788 TI - Transverse rectus abdominis musculocutaneous (TRAM) flap from TRAM flap for sequential bilateral breast reconstruction. AB - Sequential as opposed to synchronous autogenous tissue bilateral breast reconstruction imposes a dilemma because of the increasing complexity of the usually few remaining options. This fact became evident 4 years after an ipsilateral superior-pedicled lower transverse rectus abdominis musculocutaneous (TRAM) flap for left-breast reconstruction was successful in a patient who only then desired a prophylactic contralateral mastectomy but also demanded breast symmetry without implants. Without resorting to microsurgical transfers and foregoing local delay tactics, a right-breast facsimile was formed via an adaptation of breast-sharing principles. Transverse splitting of the original TRAM flap with re-elevation of the inframammary half of the reconstructed breast still maintained viability through the retained medial left rectus abdominis muscle pedicle. This second TRAM flap was immediately transposed to the opposite side without incident. Although only a fair overall aesthetic result was possible, the patient's expectation for having two "breasts" was met. PMID- 7793790 TI - Gastrocnemius muscle transposition to the femur: how high can you go? AB - The gastrocnemius muscle flap has gained wide acceptance as a reconstructive technique for management of wounds of the knee and proximal tibia. The use of the muscle as a pedicle flap to the distal and middle femur has not been well quantified, and the proximal rotation arc has been underestimated. We report the use of the island gastrocnemius pedicle flap to reach two femur defects 21 and 26 cm above the joint line, achieved by taking advantage of the favorable location of the vascular pedicle above the joint line and the individual length of the medial gastrocnemius muscle belly. Evaluation of standard arteriograms suggests the location of the medial sural artery pedicle is an average of 32 +/- 14.5 (SD) mm above the inferior border of the femur. All vessel origins were found above the joint line by radiograph. A common sural artery origin was noted in 32% of patients at a mean distance of 35 mm proximal to the joint line. Despite a wide range, 62% of sural artery origins were within 1 cm of an axis drawn through the widest point of the femoral condyles. PMID- 7793789 TI - Closure of massive chest wall defects after full-thickness chest wall resection. AB - We report an unusual repair of a massive chest wall defect resulting from resection of a chronic ulcer after radiation therapy for stage IV breast carcinoma. The defect was 690 cm2 and included the body of the sternum, 10 ribs, and the anterior portion of the diaphragm. Chest wall reconstruction was accomplished with multiple flaps: a pectoralis major advancement flap, a reversed abdominoplasty, an omental flap, and a latissimus dorsiscapular-parascapular musculofasciocutaneous (hemiback) flap. Skeletal reconstruction with prosthetic material or bone grafts was not performed in this patient. The problems associated with complex chest wall reconstructions are discussed. PMID- 7793791 TI - Internal brain herniation in a patient with Apert's syndrome. AB - Patients with Apert's syndrome typically exhibit craniosynostosis, exorbitism, midface hypoplasia, and symmetric syndactyly. There have also been occasional descriptions of the variable dysmorphology of the inner surface of the calvarium. We present a patient with Apert's syndrome who had an intracranial herniation of a portion of the frontal lobe through a ridge of ossified dura. The ridge and the gliotic cortical tissue were removed when the patient underwent repair of the hypertelorism at age six. Bone grafts for this repair were fashioned in part from the resected ridge. We believe this finding may be the result of a small dural tear that occurred during prior surgery. PMID- 7793792 TI - Cleft palate and congenital lateral alveolar synechia syndrome: case presentation and literature review. AB - Cleft palate and congenital lateral alveolar synechia syndrome remains a rare occurrence. Our patient represents only the fourth case of bilateral alveolar synechia with isolated cleft palate in the world literature and, as such, is only the second patient from the United States. More commonly, additional anomalies are associated. Just more than 50 cases involving intraoral synechiae have been reported. This group of cases has implications on fetal facial growth and cleft palate development because there are no documented cases of lateral interalveolar synechiae without cleft palate. Earlier reports can be grouped as variants along the spectrum. Theories of etiology are discussed. PMID- 7793793 TI - Cortical blindness after a failed free tissue transfer: a case report and review of the literature. AB - Cortical blindness is an uncommon but well-documented entity that results from occipital ischemia or insult. We present a case of blindness following a failed free tissue transfer and review the pertinent literature. Careful history and physical examination can usually distinguish cortical blindness from other organic or psychogenic causes. The workup centers on the exclusion of treatable concurrent pathology. Despite the dramatic presentation of cortical blindness, its treatment is generally supportive and the prognosis for full recovery is excellent. PMID- 7793794 TI - Familial Saethre-Chotzen syndrome with or without polydactyly of the toe. AB - A family with Saethre-Chotzen syndrome with or without polydactyly of the great toes is presented. Saethre-Chotzen syndrome with polydactyly of the great toes has been reported as Robinow-Sorauf syndrome. Both syndromes were observed in this family. This suggests that Saethre-Chotzen syndrome and Robinow-Sorauf syndrome fall within the same clinical spectrum, and the cause is a pleiotropic effect, which is variously expressed. PMID- 7793796 TI - Baron Larrey and cold injury during the campaigns of Napoleon. PMID- 7793797 TI - Malpractice--2015: a future fable. PMID- 7793795 TI - Pigmented basal cell carcinoma: an unusual case. AB - The case of a 66-year-old man who presented with an extensive pigmented basal cell carcinoma of the left cheek is reported. Treatment consisted of irradiation and staged surgical resections. The cosmetic result was excellent, and the patient has been free of the cheek tumor for 2 1/2 years. The numerous problems inherent in the treatment of patients with disfiguring facial skin malignancies were surmounted by a multidisciplinary team in which radiotherapy, plastic surgery, and dental services participated. PMID- 7793798 TI - Re: Secondary reconstruction of abdominal wall defects associated with exstrophy of the bladder. PMID- 7793799 TI - The silver nail. PMID- 7793800 TI - Early mortality in 100 consecutive liver resections in 96 patients with benign and malignant liver tumours. AB - This report describes the mortality in 100 liver resections performed in 96 patients for seven benign and 93 malignant liver tumours. Repeat hepatectomy was performed in four patients who developed recurrences after the first liver resection. Two patients died within 30 days. The first was a 67-year-old man who died on the 2nd postoperative day from cardiac failure. The second was a 69-year old man who died on the 4th postoperative day with liver failure caused by hepatic vascular ischaemia. There were four other hospital deaths at days 33, 40, 45 and 50. A 65-year-old lady died on day 40 from sepsis caused by small bowel infarction. A 30-year-old man died on the 33rd postoperative day owing to liver failure from accelerated hepatic lymphoma spread. A 71-year-old diabetic lady died on the 45th postoperative day from sepsis caused by an untreated subphrenic abscess. A 65-year-old lady died on day 50 from systemic candidiasis after adult respiratory distress syndrome (ARDS). Further reduction in operative mortality could be achieved by better patient selection. Liver resection still remains a major operation, but has become a safe surgical procedure. PMID- 7793801 TI - Cystic carcinoma of the breast: a trap for the unwary. AB - Cystic breast masses are a common presentation to breast clinics. While the majority of cysts can be managed by simple aspiration, a small proportion are malignant. Histology records for a 10-year period have been examined to identify patients with cystic breast carcinomas. In all, 31 patients were identified. Of these, 18 had cystic degeneration of high-grade tumours, while 13 had intracystic papillary carcinoma. Both of these tumour types were diagnosed by a combination of cyst fluid cytology and breast imaging. The prognosis of high-grade tumours was poor, while that of intracystic papillary carcinomas was excellent. After cyst aspiration, bloodstained fluid should be sent for cytology and breast imaging arranged in all patients. Patients in whom a cyst refills within 2 week of aspiration require a careful re-evaluation. Cysts in postmenopausal women should be viewed with suspicion. Excision should be performed in patients with positive cytology or imaging. PMID- 7793803 TI - The 'nodding' sign. PMID- 7793802 TI - Management of fibroadenoma of the breast. AB - Fibroadenoma is a common cause of discrete breast lumps in young women. There is agreement that fibroadenomas can be diagnosed preoperatively with a high degree of confidence and that some of the lesions thus diagnosed will resolve, possibly obviating the need for excision. There is, however, wide disagreement over the proportion of fibroadenomas that resolve spontaneously and therefore the benefit that accrues from an expectant policy. The aim of this study was to audit the management of fibroadenomas on one unit and clarify their natural history over a 5-year period. A cohort of 70 women with 87 fibroadenomas diagnosed using a triple assessment of clinical examination, cytology and imaging (sonomammography) have been followed for a minimum of 5 years. In all, 53 of the 'fibroadenomas' have been excised. In four cases the histology revealed benign disease other than fibroadenoma; there were no neoplasms. The sensitivity of cytology and sonomammography for the diagnosis of fibroadenoma were 84% and 98% respectively. Thirty-four fibroadenomas have not been excised. Of 25 fibroadenomas that have been reassessed after at least 5 years of follow-up, 13 (52%) have reduced in size, 4 (16%) are unchanged in size and 8 (32%) have grown. No patient has developed a carcinoma at the site of the presumed fibroadenoma. This study confirms that an expectant management policy of fibroadenomas has not resulted in misdiagnosis of carcinomas. Further, since a significant proportion of fibroadenomas remain static or reduce in size over a 5-year period many women can avoid excision. PMID- 7793804 TI - Management of small fragment wounds in war: current research. AB - The majority of war wounds are caused by antipersonnel fragments from munitions such as mortars and bomblets. Modern munitions aim to incapacitate soldiers with multiple wounds from very small fragments of low available kinetic energy. Many of these fragments may be stopped by helmets and body armour and this has led to a predominance of multiple wounds to limbs in those casualties requiring surgery. The development of an appropriate management strategy for these multiple wounds requires knowledge of the contamination and extent of soft tissue injury; conservative management may be appropriate. The extent of skin and muscle damage associated with a small fragment wound, the way in which these wounds may progress without intervention and their colonisation by bacteria has been determined in an experimental animal model. Results from 12 animals are presented. There was a very small (approximately 1 mm) margin of nonviable skin around the entrance wound. The amount of devitalised muscle in the wound tract was a few hundred milligrams. Some muscles peripheral to the wound track also showed signs of damage 1 h after wounding, but this improved over 24 h; the proportion of fragmented muscle fibres in the tissue around the track decreased as time went on. There was no clinical sign or bacteriological evidence of the track becoming infected up to 24 h after wounding. This preliminary work suggests that, in the absence of infection, the amount of muscle damage caused by small fragment wounds begins to resolve in the first 24 h after injury, even without surgical intervention. PMID- 7793806 TI - Digital flexor sheath injury: a new diagnostic test. AB - The diagnostic value of the transthecal digital nerve block is proposed for identifying flexor sheath injuries associated with seemingly trivial finger lacerations. Its use is described in five cases which were referred to our hand service for further exploration, with subsequent confirmation of flexor sheath and tendon injury. PMID- 7793805 TI - Flexor pollicis longus tendon injuries in children. AB - Tendon injuries to the thumb are uncommon in children. Nine children (mean age 6.1 years) with isolated complete injuries to the flexor pollicis longus (FPL) were treated with primary suture and controlled mobilisation at a major referral centre between 1985 and 1992. Five injuries occurred in zone II, two in zone III and two in zone V. One child developed sepsis and there were no cases of tendon rupture. Good or excellent results (Buck-Gramcko criteria) were achieved in seven of the nine children. Pinch grip after repair was similar to the non-injured hand. Primary repair and early controlled mobilisation of FPL leads to satisfactory results in children. PMID- 7793807 TI - Improving exposure and safety at the saphenofemoral junction. PMID- 7793809 TI - The surgery of mitral stenosis 1898-1948: why did it take 50 years to establish mitral valvotomy? PMID- 7793808 TI - Long posteromedial myocutaneous flap below-knee amputation. PMID- 7793810 TI - Clinical guidelines on the management of groin hernia in adults. PMID- 7793811 TI - Laparoscopic cholecystectomy: potential for missed pathology. PMID- 7793812 TI - An audit of the early complications of turbinectomy. PMID- 7793813 TI - Direct puncture technique for laparoscopy. PMID- 7793814 TI - Use of hand-held Doppler to avoid abdominal wall vessels in laparoscopic surgery. PMID- 7793815 TI - Traumatic rupture of the thoracic aorta: computed tomography may be a dangerous waste of time. PMID- 7793816 TI - Current attitudes to cementing techniques in British hip surgery. PMID- 7793817 TI - Experience with a knot-free absorbable subcuticular suture. PMID- 7793818 TI - War injuries during the Gulf War: experience of a teaching hospital in Kuwait. PMID- 7793819 TI - Lower limb amputation: striking the balance. PMID- 7793820 TI - Adjuvant chemotherapy for colorectal cancer. AB - Colorectal cancer is the second most common cancer in the Western world, and yet the survival after potentially curative excisional surgery has improved little over the last half century. Newer tumour prognostic markers are not superior to conventional Dukes' staging and there are currently no markers which predict response to chemotherapy. Adjuvant chemotherapy has had a chequered past, but recently a number of important prospective studies have demonstrated its proven benefit in patients with Dukes' stage C colorectal cancer. However, several issues still require clarification. (1) Do immunomodulators such as levamisole have a significant role in adjuvant chemotherapy? (2) Which patients derive most benefit from adjuvant chemotherapy? (3) Do prognostic markers have a role in predicting these patients? Approximately 30% of patients with Dukes' stage B cancers die of metastatic disease and the role of adjuvant chemotherapy in patients with these tumours seems worth exploring. Only a large randomised trial can give answers to these important questions. Such a trial would also encourage the widespread introduction of standard methods of surgical and pathological assessment. PMID- 7793822 TI - Transduodenal sphincterotomy for stenosing papillitis and massive choledocholithiasis after Billroth II gastrectomy. AB - Management of stenosing papillitis with massive cholecystodocholithiasis in patients previously operated upon with a Billroth II (B-II) type gastrectomy, is a challenging clinical problem. Endoscopic papillotomy in these patients has been described, but the success rate is low especially in the presence of a long afferent loop of the gastrojejunostomy and/or extensive adhesions. Long-standing common bile duct (CBD) stones lead to varying degrees of papillary stenosis. The latter could predispose to new stone formation because of the damaged CBD mucosa and varying degrees of stasis. In this paper we describe a simple method for intraoperative assessment of the papillary calibre and distensibility by correlation to the diameter of an inflated balloon catheter. This method has been used successfully in the management of five patients with no stone recurrence in the dilated CBD at follow-up. PMID- 7793821 TI - Luminal and humoral influences on human rectal epithelial cytokinetics. AB - Multiple genetic and environmental steps may underpin the development of human colorectal neoplasia, and experimental evidence suggests that promoters of colorectal cancer also induce colorectal epithelial cell hyperplasia. In vitro crypt cell production rate (CCPR) was measured to determine the effect of calcium, epidermal growth factor (EGF), vitamin D3 metabolites and synthetic analogues on human rectal epithelial cell proliferation. In a double-blind trial of oral calcium supplementation, CCPR was reduced by 49% in patients with familial adenomatous polyposis (FAP), but there was no effect on established neoplasia. In control tissue, the active form of vitamin D3 (1,25(OH)2D3) reduced rectal CCPR by 57% at 1 microM, 55% at 10 nM and 45% at 100 pM. Likewise, in tissue taken from patients with FAP, 1,25(OH)2D3 reduced CCPR by 52%. Vitamin D3 has profound effects on calcium metabolism, but synthetic analogues can avoid these. The effects of a synthetic analogue (MC-903) on human rectal CCPR were therefore studied. MC-903 (10(-7) M) reduced CCPR in control tissue by 51%, and in FAP tissue by 52% at 10(-6) M and 51% at 10(-7) M. In addition, MC-903 and a related analogue, EB 1089, produced a clear-cut dose-dependent inhibition of both HT-29 and Caco2 colorectal cancer cells maintained in culture. Hence, vitamin D3 and its analogues can reduce the rate of cell proliferation in normal, premalignant and malignant colorectal epithelial cells and might therefore have future therapeutic uses as chemoprotective or chemotherapeutic agents. Lastly, EGF increases CCPR by 102% in FAP tissue that expresses the EGF receptor. Thus, human colorectal cell proliferation is influenced by a variety of luminal and humoral agents and a greater understanding of these actions should help plan future treatments. PMID- 7793823 TI - Direct access surgery. AB - Evolving surgical practice in the UK is imposing increasing pressures on surgical outpatient clinics. A Direct Access Surgery (DAS) programme was evaluated in which otherwise healthy patients with simple surgical conditions presenting little diagnostic difficulty were referred directly to hospital for surgical operation without attending the outpatient department. Specific referral criteria for DAS were devised. Appropriate surgical conditions or procedures included hernias, vasectomies, cystic scrotal swellings, subcutaneous lumps and skin lesions, symptomatic gallstones, varicose veins and ingrowing toenails. Over a 12 month period, 105 patients were referred for DAS and 102 underwent operation. There was a low incidence of inaccurate diagnosis (< 2%) and inappropriate referral (< 1%). DAS was well received by both General Practitioners (GPs) and patients. Implementation of such programmes may result in considerable savings of outpatient time and resources. PMID- 7793825 TI - [Cancer of the rectum in the elderly]. PMID- 7793826 TI - [Place of surgery in the treatment of lung metastases from colorectal cancers]. AB - The authors analysed the five main series reported in the literature exclusively devoted to surgical treatment of lung metastases of colon and rectum cancers and their own experience. The classical indications, limited to solitary lesions, have been extensively modified, and resection of bilateral lesions, recurrent lesions and pulmonary lesions in patients previously operated for other extrathoracic metastases is now possible. The 5-year survival rates vary between 20 and 44% in the various series. The complete nature of the resection is an essential prerequisite to prolonged survival. The other prognostic factors are discussed: presence of lymph node invasion or raised CEA appear to carry a poor prognosis. On the other hand, the type of resection performed, the disease-free interval, the repeated nature of the pulmonary resection and the presence of previously operated extrathoracic metastases do not appear to influence survival. Opinions differ concerning the prognostic significance of disseminated pulmonary lesions, particularly when complete resection is possible. These results confirm the special place of surgery in the treatment of lung metastases of colon and rectum cancers. The operative indications are still difficult to define, but the relatively benign nature of this surgery justifies an extension of the indications. PMID- 7793824 TI - Parathyroidectomy for hyperparathyroidism associated with renal disease. AB - Between 1969 and 1993, 123 patients were accepted in this unit for surgery for refractory hyperparathyroidism associated with chronic renal failure. Subtotal parathyroidectomy was the procedure of choice. At operation, four or more parathyroids were identified in 75% of patients. Methylene blue localised additional parathyroids in 32% of initial explorations in which it was used. Coincidental thyroid pathology was found in 8.3%, including papillary carcinoma in 2.4%. No further parathyroid surgery was required in 90% of patients at a mean of 6.6 years after operation. Reoperation (10%) was more likely to be required (14.3%) when less than four glands were found than when four or more were found (8.5%). Patients continuing on dialysis were more likely to need reoperation than those with functioning renal transplants. PMID- 7793827 TI - [Colonic esophagoplasty for benign lesions]. AB - 68 patients underwent oesophageal replacement for benign disease: atresia (12), reflux oesophagitis (16), caustic stenosis (37), internal fistula (3). The transplant was the ileocolon (27), the transverse (5) or left colon (36). It was substernal (55) or posterior mediastinal (13). A by-pass was performed without oesophagectomy (51) or an interposition accompanied oesophagectomy (17). The superior anastomosis was cervical (52) or thoracic (16). The inferior anastomosis was on the stomach (46), duodenum (10) or jejunum (12). Hospital mortality was 8.8%, morbidity was 57.3%. Among the 62 survivors, 18 had another operation. At the end of the survey, 68% had near normal function. PMID- 7793829 TI - [Evolution of indications for Hartmann's operation. Reflexions on a series of 160 cases]. AB - The authors report the results and indications of 160 Hartmann's procedures performed over a period of 15 years. Between 1978 and 1992, 160 patients (90 males, 70 females), with a mean age of 72, underwent Hartmann's procedure for rectosigmoid carcinoma in 55% of cases, for complications of sigmoid diverticulitis in 36% and for other lesions in 14%. Hartmann's procedure was performed either electively (42%) or as an emergency (58%) with a mortality of 6% and 32% respectively. The majority of complications included wound infections or intraperitoneal abscess, and the overall morbidity was 30%. Re-establishment of bowel continuity was performed in 30.7% of patients, most of whom had been initially operated as an emergency for a benign lesion. These 160 cases of Hartmann's procedure represent 27% of the 590 operations performed during the same period as an emergency or electively for rectosigmoid lesion. Hartmann's procedure remains a most effective technique for emergency surgery for benign or malignant lesions with colonic septic complications, and is also indicated electively for palliative treatment of rectosigmoid carcinoma. PMID- 7793830 TI - [Pedicular traumas during laparoscopic cholecystectomy. Apropos of 5 cases]. AB - Laparoscopic cholecystectomy is now the procedure of choice for surgical removal of the gallbladder. Injury to the hepatic pedicle is the most significant complication of this procedure. Four cases of bile duct injury and one case of right hepatic artery injury were reviewed. Two complications arose from excessive use of cautery in the area of bile common duct and right hepatic artery, resulting in one case of biliary necrosis and one case of right hepatic artery pseudoaneurysm. Two injuries were due to classical confusion between the common bile duct and the cystic duct. Another injury was due to partial ligation of the common by a clip on the cystic duct. Two patients required a Roux en Y hepaticojejunostomy, two patients had a common duct repair on a T tube and one patient required emergency ligation of the right hepatic artery and suture of the duodenum. We did not observe any mortality. Morbidity consisted of one case of spontaneously resolving duodenum leakage. In the light of these cases, after having discussed the therapeutic attitudes toward these lesions. The authors suggest practical tips to prevent hepatic pedicle injuries during laparoscopic cholecystectomy. PMID- 7793831 TI - [Primary cancer of the gastric stump. Apropos of 8 cases]. AB - The authors review their experience of 8 cases of primary carcinoma of the gastric stump during the period 1989-1992. During the same period, 164 gastric cancers were treated in the same department. Mean duration between primary gastric resection and diagnosis of gastric stump carcinoma was 30 years (6 to 42 years). All patients underwent a Billroth II primary gastric resection. Only 4 patients underwent radical surgical resection of their gastric stump carcinoma; 2 patients underwent only explorative laparotomy for very advanced and unresectable gastric stump carcinoma; 2 patients were inoperable because of their general status. This series of 8 cases of gastric stump carcinoma emphases the importance of endoscopic investigations during follow-up of patients with gastric resection, in order to diagnose and treat resectable gastric stump carcinoma. PMID- 7793828 TI - [Management of primary hyperparathyroidism in case of negative cervicotomy]. AB - Negative initial cervicotomy for primary hyperparathyroidism can be due to one of two reasons: first, one gland has not been found: it was an missing adenoma on an ectopic gland. Secondly, four normal glands were found: a missing adenoma arising in a supernumerary and ectopic gland. Successful parathyroid surgery depends the on surgeon's experience, his knowledge of parathyroid gland embryology, and his perseverance to find the pathologic gland. After an unsuccessful cervicotomy, the necessity for reoperation must be discussed. Before reexploration, diagnosis of hyperparathyroidism must be reviewed, the operative notes and pathologic report of the previous operation must be studied, and localization studies must be performed in order to define the cervical or mediastinal surgical approach. PMID- 7793833 TI - [Rules of decontamination and disinfection of medicosurgical instruments in the operating room]. AB - Nosocomial infections may result from the reuse of surgical devices if adequate disinfection or sterilization measures are not employed. The first step of reprocessing occurs immediately after use in the operating room. This consists of cleaning and decontamination to eliminate organic material and to reduce the number of microorganisms, in order to protect personnel who subsequently manipulate these instruments and to facilitate the ultimate process of sterilization or disinfection. Instruments that cannot be sterilized must be submitted to "high level disinfection" to remove undesirable microorganisms. In order to guarantee the desired results of disinfection, it is very important to adopt reliable and effective protocols, chemical products with good germicidal properties and with minimal adverse effects on the personnel and the environment. The personnel involved in this delicate and important task must be thoroughly trained. If the above conditions are met, the infectious risk associated with reuse of surgical devices can be controlled. PMID- 7793832 TI - [Non-surgical treatments of hepatocellular carcinoma]. AB - Hepatocellular carcinoma has as poor prognosis. Curative surgical treatment remains the first-line treatment. However, because of the limited indications and the high recurrence rate of this cancer, nonsurgical treatments have been developed. Intraarterial chemotherapy (with or without embolization or lipiodol), although effective on tumour bulk, has not yet been demonstrated to be effective on survival in the controlled studies published to date. Ultrasound-guided percutaneous alcohol injection, which is a more recent method, is simple, inexpensive and well tolerated. The inclusion of patients into controlled therapeutic protocols remains essential for both of these methods. Outside of the context of these studies, inoperable hepatocellular carcinoma without extrahepatic metastases can be treated by chemo-embolization in the case of unilobar tumours, without portal thrombosis, or major hepatocellular insufficiency or renal failure, and by alcohol injection in the case of small tumours, limited in number, without any serious clotting disorders or abundant ascites. When these two methods are contraindicated, endocrine therapy by tamoxifen remains an alternative to symptomatic treatment. In contrast, external beam radiotherapy, systemic chemotherapy and intraarterial chemotherapy without Lipiodol or embolization are no longer indicated. Finally, internal radiotherapy by intraarterial injection of lipiodol radioactive iodine is currently under evaluation. PMID- 7793834 TI - [The intestinal capsule: a new way of investigating the small intestine]. AB - The small bowel is difficult to explore because of its location far away from the natural orifices. The aim of this study is to describe a telemetric, autonomous and multifunctional capsule (39 mm in length and 11 mm in diameter) designed according to a modular system to explore the small bowel. It consists of a central cylinder containing a location detector which allows permanent data collection concerning its position in the small bowel, the length of the small bowel and the transit velocity; secondly, several interchangeable tips allow either aspiration of a sample of intestinal juice, or release of a substance previously placed in the capsule, or to perform a mucosal biopsy. After having been swallowed by the patient, the capsule passes through the whole gut and is then recovered in the stools between 24 and 48 hours later. The preliminary study consisted of comparing, in patients undergoing a surgical procedure, the small bowel length measured by telemetry (542.3 +/- 113.8 cm) to that measured intraoperatively by the arithmetical mean of the mesenteric and antimesenteric edges (515 +/- 112.7 cm), p = 0.28. These different interchangeable working tips have already been used to determine the level of absorption of various substances, the discovery of absorption sites and the performance of mucosal biopsies without any material link between patient and the measuring or recording equipment. The main advantages of this intestinal capsule are the possibility to continuously transmit its location, its total autonomy and remote control of the desired action. PMID- 7793835 TI - [Gallbladder pneumatosis. An ultrasonic pitfall]. PMID- 7793836 TI - [Appendectomies in Bamako]. PMID- 7793837 TI - [Neonatal gastric perforation after assisted ventilation in the presence of duodenal atresia]. PMID- 7793838 TI - [Reflex ileus after placement of percutaneous gastrostomy by endoscopic approach: value of erythromycin]. PMID- 7793839 TI - [Administration of erythrocytes for the compensation of surgical blood loss in adults]. PMID- 7793840 TI - [The treatment of acute dissections of the aorta by circulatory arrest under deep hypothermia and retrograde cerebral perfusion]. AB - The use of profound hypothermia with retrograde cerebral perfusion was described by Ueda in 1988. The innovation of this technique was the retrograde perfusion of oxygenated blood at a temperature of 15 degrees C and a pressure of 25 mmHg via the superior vena cava during the circulatory arrest period. Between february 1993 and march 1994, this technique was used in 12 patients in our department, with acute dissection of the aorta present in 8 cases. In this series of 8 patients, 3 females and 5 males aged 47 to 73 (mean age 60 years)--there were 7 type I acute dissections, one of which occurred on an annulo-aortic ectasia, and 1 type III retrograde dissection with hemopericardium. Treatment consisted of 7 supracoronary tubes one of which extended as a tongue along the inner curvature of the aortic arch, and 1 Cabrol's procedure. Mean times were: extracorporeal circulation: 148 +/- 50 minutes, core cooling: 60 +/- 20 min., circulatory arrest: 34 +/- 9 min., core rewarming: 69 +/- 27 min. Average flow of retrograde perfusion was 440 +/- 350 ml/minute. Mean post operative bleeding was 650 +/- 150 ml for the first 48 hours. No patient awoke with signs of neurological deficiency. Seven patients were weaned from mechanical ventilation either on day 1 or day 2. They presented normal neurological examination. One patient in whom minor post operative disturbance postponed mechanical ventilation weaning to day 4, was neurologically intact upon examination prior to hospital discharge. One patient with no initial post operative complication, died of thrombosis of the Cabrol prosthesis at day 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793842 TI - [Mitral surgery by superior biatrial septotomy]. AB - The superior biatrial septotomy approach consists of two semicircular right atrial and septal incisions joined at the superior end of the interatrial septum and extended across the dome of the left atrium, allowing exposure of the mitral valve by reflecting the ventricular side using stay sutures. From 1991 to 1993, 81 patients underwent mitral valve surgery by this technic. Mitral valve operation was combined with other cardiac procedures in 30 patients (37%) and was performed as a second operation in 21 patients (25.9%). Duration of cardiopulmonary bypass and aortic occlusion was not significantly different from that of patients operated via a conventional left atrial approach. The five hospital deaths (6.2%) were not related to this operative approach. Only 2 patients (3.3%) with preoperative in sinus rythm were discharged in atrial fibrillation after operation. In one patient (1.6%), atrioventricular block appeared at late follow-up. There were no cases of bleeding, atrioventricular nodal dysfunction or intra-atrial shunting related to the approach. This approach provides excellent exposure of the mitral valve even in unfavorable situations such as a small left atrium, dense adhesions from previous procedures or a previously implanted aortic prosthesis, without damage to various cardiac structures due to excessive traction. No retractor or vena cava repair are required. These data support a wide application of the superior biatrial septotomy approach in mitral valve surgery. PMID- 7793841 TI - [Prognostic effect of diverse surgical parameters in significant stenoses of the left coronary trunk. Retrospective study of 185 cases]. AB - A retrospective study of 185 cases of left main coronary artery stenosis operated between 1980-01-01 and 1991-06-15 at the Limoges University Hospital Center was performed. The influence of operative procedures: cardiopulmonary bypass and aortic cross clamping times, type and number of coronary grafts, time between coronary surgery and coronary angiography, on early (before the 30th days after surgery) and late postoperative vital prognosis was studied. This study confirms in our study the poor early postoperative prognosis of: 1) cardiopulmonary bypass time over 140 min; 2) coronary bypasses in an emergency context (surgery less than 24 h after coronary angiography); 3) incomplete coronary revascularization. The nature of grafts and the aortic cross clamping time have no influence. The actuarial survival studies confirm the poor long-term postoperative prognosis of incomplete coronary revascularization; the other surgical procedures have no influence. PMID- 7793843 TI - [Thoracic tumors after treatment for Hodgkin disease]. AB - Twenty-one patients were admitted to the surgical unit for management of an intra thoracic mass following treatment of Hodgkin's disease (HD). They consisted of 14 males and 7 females, with a mean age of 34 years (range: 17-62). Seven had recurrent HD, 14 had a non-Hodgkin solid tumour. HD recurrences were treated with repeated chemotherapy with 4 prolonged survivals including 1 relapse (40 to 84 months follow-up). Non-Hodgkin tumours were 13 lung carcinomas, which were resected in 4 cases, with only 1 prolonged survival (54 months) and malignant schwannoma. HD recurrences are observed equally in both young males and females and are subsequent to a mediastinal location of the disease, after an average 3.2 years. They are located on the borders or irradiation fields. Repeated chemotherapy is effective. Carcinomas more often appear in males, at an older age, in a favorable clinical context, after an average 10.2 years. Their prognosis is very poor. Irradiation and chemotherapy contribute to their development. Long-term risks of HD treatment must be considered. PMID- 7793844 TI - [Is endoscopy of the respiratory-digestive tract under general anesthesia useful in the screening for cancer of the superior respiratory-digestive tract synchronous with lung cancer?]. AB - The frequency of lung cancers associated with synchronous head and neck malignancies can be evaluated between 1.5 to 2%. The purpose of our work was to determine if complete endoscopic head and neck examination performed under general anesthesia was superior than clinical head and neck examination for the diagnosis of these synchronous additional tumors. From july 1991 to august 1992, we realised a prospective study on 58 consecutive patients suffering from pulmonary removable lung cancers. All the patients had a clinical head and neck examination during the preoperative period. Immediately before thoracotomy a complete endoscopy of head and neck aerian and digestive tract was performed. During this last examination 18 new macroscopical lesions were discovered in 13 patients: benign lesions (n = 17), oral cavity and laryngeal dysplasia (n = 1). The one gingivolingual sulcus carcinoma, already discovered by the clinical examination, was confirmed. This study suggests that complete head and neck endoscopy is not superior than clinical examination for the diagnosis of synchronous malignancies before lung cancers removal. PMID- 7793845 TI - [Surgical treatment of pneumothorax. Study of a series of 400 cases]. AB - Surgical management is indicated for recurrent forms of pneumothorax as well as for failures of tube drainage. We report a series of 400 patients treated surgically mainly by pleural abrasion over the past 17 years. Statistical analysis of the results identifies two groups: 308 patients under the age of 45 years had surgery mainly for spontaneous idiopathic pneumothorax, where as 92 patients over the age of 45 years had surgery mainly for emphysema. In young patients, the axillary incision was preferred due to the lack of muscular sequelae and to avoid unpleasant aesthetic sequelae. Postoperative complications occurred in 60 patients (15%). The main complication was a residual pneumothorax after drain removal requiring further drainage (10%). A single recurrence occurred (0.25%). Pleural abrasion is a very effective way to treat recurrent forms of pneumothorax. PMID- 7793847 TI - [Left single-lung allotransplantation with or without bronchial artery revascularization in pigs. Development of a model with a five-week survival]. AB - After lung transplantation, immunological mechanisms are easier to understand if the pathologist can examine larger pieces of tissues than those obtained by endoscopic biopsies. The purpose of this study was to test the experimental left lung transplantation in the pig, performed with or without bronchial arterial revascularization and with a survival of 5 weeks. Three animals were only thoracotomised (sham-operated), ten were allotransplanted without and nine with- bronchial arterial revascularization. To optimize survival several clinical and paraclinical parameters were used: laboratory, immunological, endoscopic and flowmetric examinations. Seven of the nineteen transplanted animals survived until the fifth week. Long-term survival is possible and depends mainly on the development of pulmonary sepsis. We observed an increase of the pulmonary vascular resistances and pressures in the allo-transplanted animals. In these animals, histologic examination showed lymphoplasmocytic infiltration in the interalveolar walls and the number of ciliated epithelial cells decreased on the main and lobar bronchi. Our observations suggest that CD8 lymphocytic infiltration is predominant on the bronchi after transplantation and that rejection may occur in the pig. Class 2 DR Swine Leukocyte Antigen does not seem to be expressed on the bronchi in the allo-transplanted pig after 5 weeks. Finally, it is very difficult to demonstrate the patency of bronchial arterial grafts after 5 weeks and therefore to prove the influence of revascularization. PMID- 7793848 TI - [Experimental models of arterial thrombosis]. AB - Arterial thrombosis is clearly responsible for a very wide range of cardiovascular diseases, which is why many models of arterial thrombosis have been developed. These models are based on various techniques such as electrical, mechanical, biochemical, photochemical induction. They are an essential prerequisite to the understanding of molecular and cellular phenomena and are also essential to test the antithrombotic activity of new molecules before the first clinical trials in man. The large range of models means that the most appropriate model can be selected for the study of the test substance. However, the antithrombotic activity of a substance needs to be studied by several models. Most of these models induce total occlusion in which the number of parameters studied is limited. As a result of technological progress and the development of techniques such as laser and image analysers, new perspectives are now available for both basic and pharmacological research. Consequently, the already major value for these models should continue to grow over the years to come. PMID- 7793846 TI - [Closed traumas of the thorax. Assessment of two years activity at the Dakar Trauma Center]. AB - Two years after opening the Dakar Trauma Center has received 179 cases of blunt chest trauma without prehospital treatment. Road accidents were the leading cause. The initial mortality was 29 patients (16.20%) and 150 patients arrived alive and were treated. The initial mortality was primarily due to the associated extrathoracic injuries mainly hemorrhagic with hemoperitoneum in 44.82% and brain hemorrhage in 24.14% of cases. Secondly, it was due to the thoracic injuries with 41.37% of anterior flail chest and massive hemothorax in 65.51% of cases. Among the 150 patients treated, 42% had extrathoracic injuries, mainly head trauma. 56% were admitted to intensive care units with 39 chest drainages and 6 thoracotomies were performed. The mortality in this group was about 11.33%. The very high initial mortality could be reduced by the organisation of prehospital treatment to take better care of patients involved in road accidents. PMID- 7793849 TI - [Cardiac manifestations of diffuse systemic scleroderma. Apropos of 4 cases]. AB - Based on a series of four cases and a review of the literature, the authors describe the lesions of the various cardiac tissues in the course of systemic scleroderma. Pericardial involvement presents in the form of either acute pericarditis or chronic pericarditis. Pericardial tamponade is exceptional. Sclerodermal cardiomyopathy is frequent and serious and can be responsible for heart failure. Arrhythmias are frequent and may be either ventricular or supraventricular. Involvement of the conduction tissue often requires implantation of a pacemaker. Endocardial and valvular involvement is very rare. Lastly, coronary involvement appears to be fairly rare and responsible for vasospastic episodes in the coronary artery territory. PMID- 7793851 TI - [Hemangioma of the interventricular septum simulating right obstructive cardiomyopathy. Apropos of a case and review of the literature]. AB - The authors report a case of haemangioma of the interventricular septum, a rare cardiac tumour (2.8% of all primary cardiac tumours) simulating right obstructive cardiomyopathy. Based on a review of the literature, they emphasize the diversity of the clinical expression of this disease and the uncertain medium and long-term outcome of operated and nonoperated tumours. PMID- 7793850 TI - [Myxoma of atypical manifestation and morphology]. AB - The authors report a case of myxoma of the left atrium unusual by its clinical presentation, very calcified radiological appearance and histological findings. The topographic description, facilitated by transoesophageal echocardiography, is also emphasized. PMID- 7793852 TI - [Total permanent auricular paralysis. Review of the literature apropos of 109 cases]. AB - Analysis of 109 well documented cases of permanent total atrial paralysis reported in the literature illustrated the features of this arrhythmia which is a well defined entity consisting of suppression of all electrical and mechanical activity of both atria lasting for more than 6 months. Standard electrocardiogram reveals junctional bradycardia of about 40 bpm without any visible P waves and narrow supraventricular QRS complexes in 80% of cases. This diagnosis can only be confirmed by meticulous bipolar endocavitary recordings exploring all atrial walls without recording an auriculogram and by right intra-atrial and coronary sinus stimulation which proves to be ineffective. This disease has a male predominance in two-thirds of cases and a familial nature in 18% of cases. Seventy one per cent of affected subjects are under the age of 50 years. In 33% of cases, it is associated with Emery-Dreifuss muscular dystrophy, in which it constitutes a specific sign allowing this dystrophy to be differentiated from all other forms, especially facio-scapulo-humeral myopathy, and in 30% of cases, it is associated with a degenerative disease such as diabetes, amyloidosis or primary cardiomyopathy. Idiopathic dilatation of the right atrium is revealed in 15% of cases. The arrhythmia is responsible for syncope or faintness in 31% of cases, cerebral vascular accidents in 21% of cases and heart failure in 35% of cases. Cardiac activation is dependent on a junctional escape rhythm. The mechanism of the lesion responsible is atrial fibrosis which may extend to the sinoatrial node. The treatment of choice consists of implantation of a VVI or VVIR mode cardiac pacemaker in combination with anticoagulant therapy. PMID- 7793853 TI - [What attitude should be adopted in congenital heart disease in adults?]. AB - Two types of congenital heart disease are observed in adults: those discovered during childhood which may or may not have been operated, depending on their degree of severity and the surgical possibilities; those discovered during adulthood, which represent approximately 500 new cases per year and which raise particular problems: the extensive assessment which must be performed, the therapeutic solution adapted to particular situations, contraception, pregnancy, prophylaxis of endocarditis, sports or work. It is often difficult to decide to operate. Interventional catheterization represents an elegant solution in congenital heart disease in adults. PMID- 7793854 TI - [Monitoring of heparin in the treatment of deep venous thrombosis. An obsolete question?]. AB - For over 25 years, it has been the rule to monitor heparin in this indication, mostly using the TCA (or APTT) test. The goal to be reached (APTT ratio), not yet definitely defined, results from multiplying an uncertain baseline value (control APTT) by a variable factor (> or = 1.5 control value), these values being, in turn, determined using different reagents not providing uniform responses. With time, it has become clear that it was difficult to maintain the successive APTTs' within the therapeutic range and moreover, that a biologically satisfying monitoring could not, by itself, prevents from complications or clinical failures. Other classical methods experienced the same shortcomings. Low molecular weight heparin fractions have been proved to be easier to administer, since there is no need for biological monitoring. Although persisting a still unresolved problem, heparin monitoring in this indication appears to be, to date, an obsolete situation and in the process of being circumvented. PMID- 7793857 TI - Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits. AB - Using a rabbit model of pneumococcal meningitis, we compared the pharmacokinetics and bactericidal activities in cerebrospinal fluid (CSF) of older (ciprofloxacin, ofloxacin) and newer (levofloxacin, temafloxacin, CP-116,517, and Win 57273) quinolones with those of the beta-lactam ceftriaxone. All quinolones penetrated into the inflamed CSF better than ceftriaxone, and the speed of entry into CSF was closely related to their degrees of lipophilicity. At a dose of 10 mg/kg.h, which in the case of the quinolones already in use in clinical practice produced concentrations attainable in the sera and CSF of humans, ciprofloxacin had no antipneumococcal activity (delta log10 CFU/ml.h, +0.20 +/- 0.14). Ofloxacin (delta log10 CFU/ml.h, -0.13 +/- 0.12), temafloxacin (delta log10 CFU/ml.h, -0.19 +/- 0.18), and levofloxacin (delta log10 CFU/ml.h, -0.24 +/- 0.16) showed slow bactericidal activity (not significantly different from each other), while CP 116,517 (delta log10 CFU/ml.h, -0.59 +/- 0.21) and Win 57273 (delta log10 CFU/ml.h, -0.72 +/- 0.20) showed increased bactericidal activities in CSF that was comparable to that of ceftriaxone at 10 mg/kg.h (delta log10 CFU/ml.h, -0.80 +/- 0.17). These improved in vivo activities of the newer quinolones reflected their increased in vitro activities. All quinolones and ceftriaxone showed positive correlations between bactericidal rates in CSF and concentrations in CSF relative to their MBCs. Only when this ratio exceeded 10 did the antibiotics exhibit rapid bactericidal activities in CSF. In conclusion, in experimental pneumococcal meningitis the activities of new quinolones with improved antipneumococcal activities were comparable to that of ceftriaxone. PMID- 7793856 TI - Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans. AB - The aminocatechol A-3253 is active against several pathogenic fungi, including Candida albicans, Cryptococcus albidus, and Aspergillus niger. A-3253 interferes with both the in vitro biosynthesis of (1,3)-beta-glucan and the activity of topoisomerases I isolated from Candida spp. It is likely that one or more of the enzymes involved in glucan biosynthesis rather than topoisomerase I is the primary intracellular target of A-3253, since a strain of Saccharomyces cerevisiae lacking topoisomerase I is as susceptible to A-3253 as cells containing wild-type levels of topoisomerase I. However, the interaction of A 3253 with topoisomerase I in vitro is of interest since the Candida topoisomerase is more susceptible to A-3253 than is the topoisomerase I isolated from human HeLa cells. A-3253 is both a reversible inhibitor of topoisomerase I catalysis and a reversible poison of topoisomerase I, and in both reactions the fungal topoisomerase I is more susceptible than the human topoisomerase I to A-3253. In contrast, an earlier study found that the human topoisomerase I is more susceptible than the fungal topoisomerase to camptothecin (J. M. Fostel, D. A. Montgomery, and L. L. Shen, Antimicrob. Agents Chemother. 36:2131-2138, 1992). Taken together with the response to camptothecin, the greater susceptibility of the Candida topoisomerase I to A-3253 suggests that there are structural differences between the human and fungal type I topoisomerases which can likely be exploited to allow for the development of antifungal agents which act against the fungal topoisomerase and which have minimal activity against the human enzyme. PMID- 7793855 TI - Erythromycin resistance by ribosome modification. PMID- 7793859 TI - Safety, tolerance, and pharmacokinetics of atevirdine mesylate (U-87201E) in asymptomatic human immunodeficiency virus-infected patients. AB - Atevirdine mesylate (U-87201E) is a new nonnucleoside (bisheteroarylpiperazine) inhibitor of human immunodeficiency virus type 1 reverse transcriptase. In a double-blind, escalating single-dose study the safety, tolerance, and pharmacokinetics of atevirdine mesylate were investigated in 24 asymptomatic human immunodeficiency virus-seropositive male patients. Each patient received one single oral dose of atevirdine mesylate and placebo separated by an interval of 1 to 3 weeks. For each dose level (400, 800, 1,200, and 1,600 mg) six patients received drug and placebo on separate occasions. Blood samples were collected before dosing and at intervals afterward for safety evaluation and estimation of atevirdine and metabolite levels. The concentrations of atevirdine and its principal metabolite (U-89255) in serum were determined by high-performance liquid chromatography. The results of the study showed that atevirdine mesylate is well tolerated at all dose levels. No clinically significant effects on vital signs, electrocardiograms, or laboratory tests were observed. Occasional headache and nausea were reported both in the drug group and in the placebo group. The times to peak values were relatively short (0.5 to 1.0 h), suggesting a rapid absorption. The maximum concentrations of drug in serum were 1.4 microM (400 mg), 4.2 microM (800 mg), 7.3 microM (1,200 mg), and 5.8 microM (1,600 mg). The values of the pharmacokinetic parameters for atevirdine were found to have relatively large intersubject variabilities, and consequently, the study had little power to detect dose-dependent changes in the values of the pharmacokinetic parameters. The oral clearance of atevirdine tended to increase by 90% as the atevirdine mesylate doses increased from 400 to 1,600 mg, but this change in oral clearance was not statistically significant. The values of the pharmacokinetic parameters determined in the study were similar to those found in a previous single-dose study in healthy volunteers. PMID- 7793860 TI - Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model. AB - Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alone. Four other combined regimens, CLARI combined with ethambutol (EMB), rifabutin (RBT), or both EMB and RBT during the entire 16 weeks of treatment or with AMIKA administered in an initial 2-week course showed bactericidal activity not significantly greater than that of CLARI alone. After 16 weeks of treatment, CLARI-resistant mutants were isolated from the majority of mice that had been treated with CLARI alone, CLARI-RBT, CLARI-EMB, or CLARI-EMB-RBT, as was the case for untreated controls, but the frequencies of occurrence of mutants were significantly greater in the groups treated with these combinations or CLARI alone. On the other hand, no CLARI-resistant mutants were isolated from the mice that had been treated with the combination of CLARI plus an initial 4 or 8 weeks of AMIKA and were isolated from only a tiny proportion of mice that had been treated with CLARI plus an initial 2 weeks of AMIKA. Therefore, only treatment with CLARI combined with an initial 4 or 8 weeks of AMIKA but not combined with RBT or EMB or both, could enhance the activity of the drug treatment and prevent the selection of CLARI-resistant mutants. PMID- 7793858 TI - Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. AB - A study was performed to assess the in vivo relevance of the in vitro antagonism between fluconazole and amphotericin B against Candida albicans. Combinations of fluconazole and amphotericin B were explored for their efficacies against acute (100% mortality in 2 to 5 days) or less acute (100% mortality in 30 days) invasive candidiasis infections in mice with healthy immune systems and immunocompromised mice. Treatment efficacy was assessed by protection from mortality and/or a reduction in the fungal burden in tissue. In models of acute infection in mice with healthy immune systems or less acute infection in immunocompromised mice, combinations of fluconazole and amphotericin B were superior to fluconazole alone, and the effects were at least additive. Combination therapy was at least as efficacious as amphotericin B alone. In a different model of less acute infection in mice with healthy immune systems, combinations of fluconazole and amphotericin B showed no interactions and were no better than either drug alone. We conclude that combination therapy with fluconazole and amphotericin B is not antagonistic in vivo, in contrast to published in vitro studies, and, consequently, suggest that combination therapy should be considered in the management of clinical candidiasis. PMID- 7793862 TI - Comparative complement selection in bacteria enables screening for lead compounds targeted to a purine salvage enzyme of parasites. AB - Expression plasmids encoding the hypoxanthine phosphoribosyltransferases (HPRTs) of Plasmodium falciparum, Schistosoma mansoni, Tritrichomonas foetus, and Homo sapiens were subcloned into genetically deficient Escherichia coli that requires complementation by the activity of a recombinant HPRT for growth on semidefined medium. Fifty-nine purine analogs were screened for their abilities to inhibit the growth of these bacteria. Several compounds that selectively altered the growth of the bacteria complemented by the malarial, schistosomal, or tritrichomonal HPRT compared with the growth of bacteria expressing the human enzyme were identified. These results demonstrate that the recombinant approach to screening compounds by complement selection in a comparative manner provides a rapid and efficient method for the identification of new lead compounds selectively targeted to the purine salvage enzymes of parasites. PMID- 7793863 TI - Quantitative assessment of antimalarial activities from Malaysian Plasmodium falciparum isolates by modified in vitro microtechnique. AB - Malaysian, TGR (Thailand), and Gambian (West African) Plasmodium falciparum isolates were cultured in vitro by the candle jar method and were characterized for their susceptibilities to present antimalarial drugs by the modified in vitro microtechnique. Results showed that 93 and 47% of the Malaysian isolates were resistant at 50% inhibitory concentrations of 0.1415 to 0.7737 and 0.1025 to 0.1975 microM, respectively, while the rest were susceptible to choloroquine and cycloguanil at 0.0376 and 0.0306 to 0.0954 microM, respectively. All isolates were susceptible to mefloquine, quinine, and pyrimethamine at 0.0026 to 0.0172, 0.0062 to 0.0854, and 0.0149 to 0.0663 microM, respectively. In contrast, the Gambian isolate was susceptible to multiple drugs at 0.0024 to 0.0282 microM; TGR was resistant to chloroquine at 0.8147 microM but was susceptible to mefloquine, quinine, cycloguanil, and pyrimethamine at 0.0024, 0.0096, 0.0143, and 0.0495 microM, respectively. PMID- 7793861 TI - Mechanism of tonB-dependent transport of KP-736, a 1,5-dihydroxy-4-pyridone substituted cephalosporin, into Escherichia coli K-12 cells. AB - The mechanism of transport of KP-736, a novel cephalosporin with a 1,5-dihydroxy 4-pyridone moiety at the C-7 position, into the Escherichia coli K-12 cell was investigated by determining the susceptibilities of iron transport mutants to KP 736. The tonB mutant showed a higher degree of resistance to KP-736, indicating that KP-736 was incorporated into E. coli cells via the tonB-dependent iron transport system. The product of the exbB gene was also necessary for the maximal antibacterial potency of KP-736. Cir-lacking and Fiu-lacking mutants showed a moderate level of resistance to KP-736. However, mutants lacking any one of the proteins FepA, FecA, FhuA, and FhuE did not show any increased resistance to KP 736. Two types of spontaneous mutants (e.g., KT1004 and KT1011) could be isolated from cir and fiu mutants by selection for KP-736 resistance and showed the same level of resistance to KP-736 as a tonB mutant. KT1004 showed tonB phenotypes, resistance to phage phi 80, and loss of FecA, whereas KT1011 did not. KT1011 lost the ability to express both Cir and Fiu proteins. These results indicate that the Cir and Fiu outer membrane proteins are involved specifically in the tonB dependent transport process of KP-736. Against OmpF- and OmpC-deficient transformants producing various groups of beta-lactamases, KP-736 was more effective than the other cephalosporins tested. PMID- 7793864 TI - Characterization of an LysR family protein, SmeR from Serratia marcescens S6, its effect on expression of the carbapenem-hydrolyzing beta-lactamase Sme-1, and comparison of this regulator with other beta-lactamase regulators. AB - Serratia marcescens S6 produces a chromosomally encoded carbapenem-hydrolyzing class A beta-lactamase, Sme-1 (T. Naas, L. Vandel, W. Sougakoff, D. M. Livermore, and P. Nordmann, Antimicrob. Agents Chemother. 38:1262-1270, 1994). Upstream from smeA we identified a second open reading frame (EMBL accession number Z30237). This encodes a 33.1-kDa protein, SmeR, which has a high degree of homology with NmcR, the LysR regulatory protein of the only other sequenced carbapenem hydrolyzing class A beta-lactamase, NmcA from Enterobacter cloacae NOR-1. It is weakly related to AmpR of the chromosomal cephalosporinase regulatory systems described in E. cloacae, Yersinia enterocolitica, Citrobacter freundii, and Pseudomonas aeruginosa and is very weakly related to other LysR-type regulators of class A beta-lactamases. SmeR is a weakly positive regulator for Sme-1 expression in the absence of or in the presence of beta-lactam inducers. The -35 and -10 regions of smeR are in the opposite orientations and are face-to-face relative to the smeA promoter. SmeR acts similarly to NmcR and not as the AmpR regulators described for class C beta-lactamase systems. SmeR is a weak inducer in the absence or presence of beta-lactams. As was found for the AmpC-AmpR and NmcA-NmcR systems, a putative SmeR-binding site was present upstream from the beta-lactamase gene promoter regions. beta-Galactosidase activity from a smeR lacZ translational fusion was expressed constitutively and decreased in the presence of SmeR from a coresident plasmid, suggesting that SmeR is autogeneously controlled. Finally, beta-lactams did not affect the expression of SmeR, which is the second regulator of a class A carbapenem-hydrolyzing beta-lactamase to be identified. PMID- 7793865 TI - French multicenter study involving eight test sites for radiometric determination of activities of 10 antimicrobial agents against Mycobacterium avium complex. AB - The radiometric BACTEC 460-TB methodology has filled an increased need in the screening of a wide range of antimicrobial agents against Mycobacterium avium (MAC) isolates on a patient-to-patient basis. In this context, a multicenter study involving eight test sites across France was performed to determine the MICs of 10 antimicrobial agents for MAC organisms. The aim of the investigation was to compare the in vitro activities of D-cycloserine, ethambutol, ethionamide, rifampin, amikacin, streptomycin, ciprofloxacin, sparfloxacin, clofazimine, and clarithromycin against MAC isolates. All of the test sites received the same clinical isolates of MAC, and the MICs were determined by a common protocol. The overall interlaboratory reproducibility of the MICs within +/- 1 dilution of the modal MICs varied from 79.70 to 100% (mean, 95.2% +/- 2.1%), whereas overall agreement of the MICs among the test sites varied from a mean of 91% +/- 4.1% to a mean of 98 +/- 1.3%. We confirmed that the proposed methodology is easy, accurate, and sufficiently reproducible to be used routinely in a clinical laboratory. Despite variations in the MICs of the same drug among strains, no link between the origin of MAC isolates (from human immunodeficiency virus positive or -negative patients) and their drug susceptibilities was established. On the basis of the MICs that inhibited 50 and 90% of isolates tested for the drugs used, clarithromycin, clofazimine, ethambutol, and streptomycin were the most uniformly active against MAC; this was followed by amikacin, rifampin, and sparfloxacin. On the other hand, ciprofloxacin, D-cycloserine, and ethionamide showed only marginal in vitro activities. PMID- 7793866 TI - Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa. AB - Three types of multiple-drug-resistant mutants which were phenotypically similar to previously described nalB, nfxB, and nfxC mutants were isolated from Pseudomonas aeruginosa PAO1 and two clinical isolates. Type 1 (nalB-type) mutants showed cross-resistance to meropenem, cephems, and quinolones. They overproduced an outer membrane protein with an apparent molecular mass of 50 kDa (OprM). Type 2 (nfxB-type) mutants showed cross-resistance to quinolones and new cephems, i.e., cefpirome and cefozopran, concomitant with overproduction of an outer membrane protein with an apparent molecular mass of 54 kDa (OprJ). Type 3 (nfxC type) mutants showed cross-resistance to carbapenems and quinolones. They produced decreased amounts of OprD and increased amounts of a 50-kDa protein (OprN), which was almost the same molecular weight as that of OprM, but it was distinguishable from OprM by its heat modifiability on sodium dodecyl sulfate polyacrylamide gel electrophoresis. In the presence of salicylate, the parent strains showed an increased level of resistance to carbapenems and quinolones and produced decreased amounts of OprD and increased amounts of OprN. Salicylate caused the repression of OprJ production and the loss of resistance to cefpirome and cefozopran in two of the three OprJ-overproducing mutants, although salicylate slightly increased the level of resistance in the parent strains. The changes in susceptibilities were transient in the presence of salicylate. These data suggest that at least three different outer membrane proteins, OprM, OprJ, and OprN, are associated with multiple drug resistance in P. aeruginosa. PMID- 7793867 TI - Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. AB - Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations. PMID- 7793868 TI - Fluconazole concentrations in saliva from AIDS patients with oropharyngeal candidosis refractory to treatment with fluconazole. AB - Fluconazole (FCZ) has been extensively used as a primary therapy for oropharyngeal candidosis in AIDS patients. Clinical resistance to FCZ is now encountered, often related to decreased susceptibility of the isolate in vitro. We wondered if low levels in saliva play a role in the therapeutic failure, especially in patients complaining of dry mouth. Sixteen AIDS patients treated for oropharyngeal candidosis with FCZ were studied. MICs for the isolates were determined. Serum and saliva samples were collected to measure FCZ levels with a bioassay using paper disks loaded with the clinical specimens. We showed that (i) paper disks were convenient for collecting saliva in patients with dry mouth; (ii) levels in saliva depended on the FCZ dosage regimen but did not correlate with the response to therapy; (iii) correlation between concentrations in saliva and serum was poor and independent of clinical response to treatment, other therapies, or decreased salivation; and (iv) levels in saliva were always lower than MICs in patients who failed to respond to treatment. In conclusion, therapeutic failures are more likely to be related to in vitro resistance of the isolate to FCZ or insufficient dosage regimen than to decreased salivary secretion. PMID- 7793869 TI - Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. AB - A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease. PMID- 7793870 TI - Safety and bioequivalency of three formulations of respiratory syncytial virus enriched immunoglobulin. AB - Respiratory syncytial virus (RSV) causes serious illness (lower respiratory illness) in preterm infants. RSV antibody-enriched immunoglobulin (RSVIG) that was lyophilized (LYO) protected against RSV lower respiratory illness. The Food and Drug Administration now requires an additional viral inactivation step (VI). We compared LYO, LYO-VI, and a more convenient liquid RSVIG (LIQ-VI) in 30 preterm infants (median age, 7 months; median weight, 5.4 kg). Infants were randomized to receive LYO (n = 10), LYO-VI (n = 10), or LIQ-VI (n = 10) in monthly infusions of 750 mg/kg of body weight per dose (December to March). Children were monitored closely for adverse reactions to RSVIG and for RSV illness. PMID- 7793872 TI - Should Pseudomonas aeruginosa isolates resistant to one of the fluorinated quinolones be tested for the others? Studies with an experimental model of pneumonia. AB - A clinical isolate of Pseudomonas aeruginosa resistant to pefloxacin (Pef) but susceptible to ciprofloxacin (Cip) was studied to compare the in vitro and in vivo activities of Pef, ofloxacin (Ofl), and Cip. The time-kill curve method showed no bactericidal activity for Pef and Ofl, but a reduction of 4 log10 CFU/ml was achieved with Cip at 1 h. A model of experimental P. aeruginosa pneumonia was used to evaluate in vivo the relevance of the difference in susceptibility observed in vitro. At 36 h, a 100% cumulative survival rate was observed in Cip-treated rats, which was far higher than the survival rate obtained with Pef (53%) or Ofl (46%) (P < 0.001). At 4 h, no bacteremia was observed in Cip-treated rats, whereas 93% of the Pef-treated rats and 80% of the Ofl-treated rats were bacteremic (P < 0.001). The best pulmonary bacterial clearance was observed with Cip. Interestingly, Pef and Ofl, to which the strain was resistant in vitro, showed a fairly good in vivo activity despite sub-MIC concentrations. Cip was more effective than Pef and Ofl in terms of pulmonary and systemic bactericidal activity and provided the best survival rate in animals. We conclude that differences between the different quinolones in terms of the organism's sensitivity assessed in vitro may be relevant and that it might be useful to reconsider the use of a quinolone to which P. aeruginosa shows resistance if the organism shows sensitivity to no other agent. PMID- 7793871 TI - Effect of cefodizime and ceftriaxone on phagocytic function in patients with severe infections. AB - Thirty patients with severe bacterial infections were treated with 50 mg of cefodizime per kg of body weight once daily or 50 mg of ceftriaxone per kg once daily for 10 +/- 3 days. The effect of cefodizime and ceftriaxone on the phagocytic capacity and generation of reactive oxygen intermediates after phagocytosis by granulocytes was assessed prior to, during, and after therapy. Flow cytometry was used to study phagocytic capacity by measuring the uptake of fluorescein-labeled bacteria. The generation of reactive oxygen intermediates after phagocytosis was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Prior to therapy, patients in both groups exhibited a decreased capacity to phagocytize Escherichia coli and subsequently to generate reactive oxygen intermediates. Granulocyte function increased after the initiation of therapy and normalized within 7 days for the ceftriaxone-treated patients and within 3 days for the cefodizime group (P < 0.05). In the cefodizime group, an enhancement of phagocytic capacity was observed 14 days after the initiation of therapy (P < 0.05). Prior to therapy, phagocytic capacity was significantly correlated with the generation of reactive oxygen products (r = 0.674 and P < 0.005). PMID- 7793873 TI - In vitro and ex vivo activities of antimicrobial agents used in combination with clarithromycin, with or without amikacin, against Mycobacterium avium. AB - MICs of clarithromycin, amikacin, isoniazid, rifabutin, ciprofloxacin, sparfloxacin, ethambutol, and clofazimine were determined for six isolates of Mycobacterium avium complex (MAC) from AIDS patients both by the radiometric method and by an ex vivo model of infection in human macrophages. The median MICs in macrophages were similar or slightly lower than values found in broth, except for amikacin, which had slightly higher MICs inside the cells. Combinations of clarithromycin with other antimicrobial agents showed that clarithromycin clofazimine and clarithromycin-rifabutin were synergistic on five of six strains while clarithromycin-amikacin and clarithromycin-isoniazid were antagonistic on one and two strains, respectively. The addition of amikacin made the combinations of clarithromycin-clofazimine and clarithromycin-ethambutol synergistic against all the MAC strains. In the macrophage model, the combination of clarithromycin clofazimine (mean survival, 21%) and clarithromycin-rifabutin (mean survival, 29%) showed a strong reduction in viable counts compared with single drugs, while clarithromycin-amikacin was less active than single drugs alone. In general, the addition of amikacin did not improve the activity of the combinations, except for clarithromycin-isoniazid-amikacin (mean survival, 19%), which was significantly more active than either clarithromycin-isoniazid or clarithromycin-amikacin. The use of the macrophage model can suggest new combinations of antimicrobial agents with anti-MAC activity which, on the basis of their in vitro effectiveness, would probably be disregarded for assay in animal models. PMID- 7793874 TI - New mobile gene cassettes containing an aminoglycoside resistance gene, aacA7, and a chloramphenicol resistance gene, catB3, in an integron in pBWH301. AB - The multidrug resistance plasmid pBWH301 was shown to contain a sull-associated integron with five inserted gene cassettes, aacA7-catB3-aadB-oxa2-orfD, all of which can be mobilized by the integron-encoded DNA integrase. The aadB, oxa2, and orfD cassettes are identical to known cassettes. The aacA7 gene encodes a protein that is a member of one of the three known families of aminoglycoside acetyltransferases classified as AAC(6')-I. The chloramphenicol acetyltransferase encoded by the catB3 gene is closely related to members of a recently identified family of chloramphenicol acetyltransferases. The catB3 gene displays a relatively high degree of sequence identity to a chromosomally located open reading frame in Pseudomonas aeruginosa, and this may represent evidence for the acquisition by a cassette of a chromosomal gene. PMID- 7793875 TI - Recognition of multiple effects of ethambutol on metabolism of mycobacterial cell envelope. AB - Ethambutol is known to rapidly inhibit biosynthesis of the arabinan component of the mycobacterial cell wall core polymer, arabinogalactan (K. Takayama and J. O. Kilburn, Antimicrob. Agents Chemother. 33:1493-1499, 1989). This effect was confirmed, and it was also shown that ethambutol inhibits biosynthesis of the arabinan of lipoarabinomannan, a lipopolysaccharide noncovalently associated with the cell wall core. In contrast to cell wall core arabinan, which is completely inhibited by ethambutol, synthesis of the arabinan of lipoarabinomannan was only partially affected, demonstrating a differential effect on arabinan synthesis in the two locales. Further studies of the effect of ethambutol on cell wall biosynthesis revealed that the synthesis of galactan in the cell wall core is strongly inhibited by the drug. In addition, ethambutol treatment resulted in the cleavage of arabinosyl residues present in the mycobacterial cell wall; more than 50% of the arabinan in the cell wall core was removed from the wall 1 h after addition of the drug to growing mycobacterial cultures. In contrast, galactan was not released from the cell wall during ethambutol treatment. The natural function of the arabinosyl-releasing enzyme remains unknown, but its action in combination with inhibition of synthesis during ethambutol treatment results in severe disruption of the mycobacterial cell wall. Accordingly, ethambutol-induced damage to the cell wall provides a ready molecular explanation for the known synergetic effects of ethambutol with other chemotherapeutic agents. Nevertheless, the initial direct effect of ethambutol remains to be elucidated. PMID- 7793876 TI - Mechanism of enhanced antipseudomonal activity of BO-2727, a new injectable 1 beta-methyl carbapenem. AB - The mechanism of the enhanced activity of BO-2727 against imipenem-resistant Pseudomonas aeruginosa was studied by using a set of four isogenic strains derived from beta-lactamase-deficient P. aeruginosa PAO4089 (blaJ blaP). Complementation of the blaJ and blaP mutations conferred greater resistance to biapenem, panipenem, and imipenem than to BO-2727 and meropenem, most notably in the outer membrane protein D2-deficient strain. The higher levels of resistance to biapenem, panipenem, and imipenem can be explained by the slow but significant hydrolysis by beta-lactamase, whereas the reduced levels of resistance to BO-2727 and meropenem would be attributable to their stability in the presence of high levels of beta-lactamase and the fact that they cause only low induction of beta lactamase. It is also noted that the activity of BO-2727 against the beta lactamase-deficient strain was less affected by the loss of the D2 porin than was that of meropenem, indicating that BO-2727 in comparison with meropenem can overcome an intrinsic resistance caused by the loss of D2. Moreover, comparative in vitro resistance studies have shown that BO-2727 and meropenem selected fewer resistant cells than other carbapenems. In conclusion, BO-2727 exhibited improved activity against imipenem-resistant P. aeruginosa, probably because of its ability to overcome loss of the D2 porin and beta-lactamase hydrolysis. PMID- 7793878 TI - Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism? AB - Mersacidin is an antibiotic peptide produced by Bacillus sp. strain HIL Y 85,54728 that belongs to the group of lantibiotics. Its activity in vivo against methicillin-resistant Staphylococcus aureus strains compares with that of the glycopeptide antibiotic vancomycin (S. Chatterjee, D. K. Chatterjee, R. H. Jani, J. Blumbach, B. N. Ganguli, N. Klesel, M. Limbert, and G. Seibert, J. Antibiot. 45:839-845, 1992). Incubation of Staphylococcus simulans 22 with mersacidin resulted in the cessation of growth and slow lysis. Biosyntheses of DNA, RNA, and protein were not affected, whereas incorporation of glucose and D-alanine was inhibited and a regular reduction in the level of cell wall thickness was observed. Thus, unlike type A lantibiotics, mersacidin does not form pores in the cytoplasmic membrane but rather inhibits cell wall biosynthesis. Comparison with tunicamycin-treated cells indicated that peptidoglycan rather than teichoic acid metabolism is primarily affected. Mersacidin caused the excretion of a putative cell wall precursor into the culture supernatant. The formation of polymeric peptidoglycan was effectively inhibited in an in vitro assay, probably on the level of transglycosylation. In contrast to vancomycin, the activity of mersacidin was not antagonized by the tripeptide diacetyl-L-Lys-D-Ala-D-Ala, indicating that on the molecular level its mode of action differs from those of glycopeptide antibiotics. These data together with electron microscopy suggest that mersacidin acts on a novel target, which opens new perspectives for the treatment of methicillin-resistant S. aureus. PMID- 7793877 TI - Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains. AB - The antibacterial activity of nitroxoline (NIT), an antibiotic used in the treatment of acute or recurrent urinary tract infections caused by Escherichia coli, is decreased in the presence of Mg2+ and Mn2+ but not Ca2+. In order to elucidate the interaction between this drug and the divalent cations, spectrophotometric studies based on the natural absorption of the nitroxoline moiety were conducted. In the presence of the divalent metal ions, a shift in the NIT A448 suggested the formation of drug-ion complexes, for which the stability followed the order Mn2+ > Mg2+ > Ca2+. A clear correlation was found between the chelating property and antibacterial activity of NIT; both were pH dependent. A convenient colorimetric method for the determination of NIT uptake by bacterial cells was also developed. Uptake was energy independent and showed biphasic kinetics: a rapid association with cells and then a slower increase in cell associated NIT which reached a plateau. NIT uptake was reduced in the presence of magnesium. The implications of metal ion complexation and pH on the clinical efficacy of NIT are discussed. PMID- 7793879 TI - Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451). AB - Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii. PMID- 7793881 TI - In vitro activity and killing effect of DX-8739, a new carbapenem, compared with those of meropenem and imipenem against multiresistant Pseudomonas aeruginosa. AB - DX-8739 is a new dehydropeptidase I-stable carbapenem. In order to evaluate its activity in comparison with those of meropenem and imipenem, 147 multiresistant Pseudomonas aeruginosa isolates acquired nosocomially were simultaneously exposed to the actions of the three carbapenems in vitro, whereas to compare their killing effects on 14 strains, 56 killing curve studies were performed. Overall DX-8739 was found to possess inhibitory activity as well as bactericidal activity statistically superior to those of meropenem and imipenem. At a concentration of 4 micrograms/ml, 106 strains (72.1%) were found to be imipenem resistant; 33 and 27.4% of these strains were inhibited by DX-8739 and meropenem, respectively, a statistically significant difference (P < 0.05). DX-8739 was also shown to possess intrinsic activity in vitro superior to those of meropenem and imipenem against the imipenem-susceptible population of strains. However, no statistically significant difference regarding the comparative killing activities of the three studied carbapenems was observed. Following exposure to carbapenem for 24 h, 33.3, 44.4, and 70% of the strains which survived became resistant to DX-8739, meropenem, and imipenem, respectively. The reported results demonstrate the significant activity of DX-8739 against multiresistant P. aeruginosa strains acquired nosocomially. The mechanism of action of DX-8739 on P. aeruginosa is unknown, and various hypotheses that might explain its in vitro superiority over meropenem and imipenem are proposed. PMID- 7793880 TI - Therapy of Mycobacterium avium complex infections in beige mice with streptomycin encapsulated in sterically stabilized liposomes. AB - Mycobacterium avium complex (MAC) causes serious opportunistic infections in AIDS patients. Previous studies with MAC-infected beige mice have indicated that weekly administration of liposome-encapsulated streptomycin can reduce significantly the CFU in the liver and spleen. We examined whether streptomycin encapsulated in recently developed sterically stabilized liposomes with prolonged circulation times would have a therapeutic effect in this animal model. Two liposome types with prolonged circulation (polyethyleneglycol distearoylphosphatidylethanolamine [PEG-DSPE]-distearoylphosphatidylcholine [DSPC]-cholesterol [chol] or phosphatidylinositol [PI]-DSPC-chol) and conventional liposomes (phosphatidylglycerol [PG]-phosphatidylcholine [PC]-chol) encapsulating streptomycin and administered twice weekly were bactericidal to MAC strain 101 in the spleen when the level of infection after treatment was compared with the level of infection before treatment. PI-DSPC-chol and PG-PC-chol liposomes encapsulating streptomycin were bactericidal in the liver. Although PG PC-chol or PEG-DSPE-DSPE-chol liposomes encapsulating streptomycin were not bactericidal in the lungs, they reduced the level of MAC infection by more than 3 orders of magnitude compared with the level of MAC infection in untreated controls. PMID- 7793882 TI - Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity. AB - Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs. PMID- 7793883 TI - Antigenic properties and immunoelectron microscopic localization of Mycobacterium fortuitum beta-lactamase. AB - Mycobacterium fortuitum is a fast-growing Mycobacterium species which produces a beta-lactamase involved in the intrinsic resistance of the microorganism to beta lactam antibiotics. An anti-beta-lactamase serum against the purified enzyme was raised in rabbits. Antibody binding was specific for native beta-lactamase, and enzyme activity was partially inhibited by the serum; furthermore, cross reactions with denatured class A beta-lactamases were observed. This serum was used as a probe in immunogold labeling for the localization of the cell-bound beta-lactamase in both the low-level producer ATCC 19542 (parental strain) and the overproducer mutant D316. By the combination of preembedding immunogold labeling and replica technique, it was shown that the beta-lactamase was uniformly distributed on the whole external cell surface, where it appeared to be associated with a Tween 80-removable capsule-like material. Compared with the parental strain, a much higher level of expression of surface enzyme was observed in strain D316. Surface labeling was more intense in the stationary phase of growth than in exponentially growing cells. The data obtained are interpreted in the context of the intrinsic resistance of M. fortuitum to beta-lactam antibiotics. PMID- 7793884 TI - (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection. AB - The antiviral efficacy of acyclic nucleoside phosphonates, including 9-(2 phosphonylmethoxyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-2,6 diaminopurine [(R)-PMPDAP] against feline immunodeficiency virus (FIV) infection was determined. (R)-PMPDAP showed the highest selectivity index (> 2,000) in vitro. Treatment of experimentally FIV-infected asymptomatic cats with PMEA or (R)-PMPDAP had no effect on the CD4+/CD8+ ratio. However, mean plasma viral RNA concentrations decreased significantly in the (R)-PMPDAP-treated cats. Our data show that, in comparison to PMEA, (R)-PMPDAP is a more potent and less toxic inhibitor of FIV replication both in vitro and in vivo. PMID- 7793886 TI - Bioluminescence method to evaluate antimicrobial agents against Mycobacterium avium. AB - Plasmid pLUC10, carrying the firefly luciferase gene, was transformed by electroporation into Mycobacterium avium A5. Bioluminescence production by strain A5(pLUC10), as measured in a microdilution plate luminometer, was approximately 1 relative light unit per 2 x 10(6) viable bacilli, whereas it was 0.0005 relative light unit for an equal number of parental cells. The susceptibility of strain A5(pLUC10) to eight concentrations of each of eight antimicrobial agents was evaluated by the luciferase microplate assay in parallel with a conventional broth macrodilution method with antimicrobial agents. Decreases in bioluminescence to levels that were < or = 10% of those of drug-free controls were observed in microplate wells containing inhibitory concentrations of drugs in as few as 3 days. The close correlation of these inhibitory concentrations with the MICs determined by a conventional broth macrodilution method suggests that the luciferase microplate method may offer a convenient and reliable means of evaluating the in vitro activities of antimicrobial agents against the M. avium complex. PMID- 7793885 TI - Comparison of activities of fluoroquinolones in murine macrophages infected with Mycobacterium tuberculosis. AB - In this study the compounds levofloxacin and sparfloxacin, as well as three experimental compounds (AMQ2, AMQ4, and AMQ5), were compared with isoniazid and rifabutin in terms of their capacity to inhibit the intracellular growth of the drug-susceptible Mycobacterium tuberculosis strain Erdman and the isoniazid resistant katG gene-negative strain 24 within monolayers of mouse bone marrow derived macrophages. Both levofloxacin and sparfloxacin, as well as compound AMQ4, had substantial activity in this physiologically relevant model, further confirming the potential usefulness of this class of compounds in the therapy of tuberculosis. PMID- 7793887 TI - Potential use of a simplified method for determination of itraconazole levels in plasma and esophageal tissue by using high-performance liquid chromatography. AB - A simplified high-performance liquid chromatography assay was developed for determination of itraconazole levels in plasma and esophageal tissue in four patients with AIDS who had been receiving daily oral doses of 100 mg of itraconazole in solution for at least 3 weeks for therapy of esophageal candidiasis. Itraconazole levels were about three times higher in esophageal tissue than in plasma (means +/- standard errors of 0.69 +/- 0.50 micrograms/g and 0.24 +/- 0.16 micrograms/ml, respectively; P = 0.04). This method is quick (it requires only 1 h for completion) and sensitive (the limits of detectability for itraconazole in plasma and esophageal tissue are 0.005 micrograms/ml and 0.01 micrograms/g, respectively), and it can be reliably used in clinical and research settings (accuracy, > 95%; absolute recovery from biological samples, 80 to 90%; coefficient of variation, 3.3 to 6.6%). PMID- 7793888 TI - Susceptibilities of Chlamydia trachomatis isolates causing uncomplicated female genital tract infections and pelvic inflammatory disease. AB - The in vitro susceptibilities of 45 recent clinical isolates of Chlamydia trachomatis obtained from women with asymptomatic genital tract infection, mucopurulent cervicitis, or pelvic inflammatory disease to doxycycline, azithromycin, ofloxacin, and clindamycin were determined. In addition, susceptibilities of 12 isolates to amoxicillin and trimethoprim-sulfamethoxazole were also determined. Isolates also were serotyped with a panel of monoclonal antibodies specific for chlamydial major outer membrane protein; 24 of 45 (53%) belonged to serovars Ia and E. For all isolates, the MIC range of doxycycline was 0.008 to 0.06 micrograms/ml, for trimethoprim-sulfamethoxazole it was 0.03 to 0.25 micrograms/ml, for azithromycin it was 0.125 to 2.0 micrograms/ml, for ofloxacin it was 0.5 to 1.0 micrograms/ml, for clindamycin it was 0.25 to 2.0 micrograms/ml, and for amoxicillin it was 0.25 to 4.0 microgram/ml. The ranges of minimum chlamydiacidal concentrations were generally 1 to 4 dilutions above the MICs of most agents, with a rank order similar to those of the MICs. Comparing the minimum chlamydiacidal concentrations for 90% of isolates tested, isolates causing asymptomatic infection belonged to a greater variety of serovars and were relatively more susceptible to doxycycline and azithromycin than isolates causing mucopurulent cervicitis or pelvic inflammatory disease; these differences in susceptibility were not detected among the other study agents. These data indicate that additional studies are needed to better define the apparent association of certain chlamydial serovars with the clinical severity of disease and the in vitro susceptibilities to certain antimicrobial agents. PMID- 7793890 TI - Use of cryomicrotomy to study gastric diffusion of amoxicillin in guinea pigs. AB - Cryomicrotomy has been used as a new technique for removing gastric mucosae from adult guinea pigs for the study of amoxicillin secretion across gastric mucosae. This method allowed a very regular thickness of the removed surface layer of mucosa to be obtained with good reproducibility. Gastric superficial mucosa concentrations and gastric juice concentrations of amoxicillin were determined 1, 2, and 4 h after intramuscular administration (50 mg/kg) in 21 guinea pigs by a microbiological method. No antibiotic was detected in gastric samples at 4 h, except for a low-level mucosal concentration in one animal, thus indicating the short time that amoxicillin is present in gastric samples. PMID- 7793889 TI - In vitro effects of sulfadiazine and its metabolites alone and in combination with pyrimethamine on Toxoplasma gondii. AB - Sulfadiazine and the metabolites N4-acetyl-sulfadiazine, 4-OH-sulfadiazine, 5-OH sulfadiazine, 5-OH-glucuronide-sulfadiazine, and 5-OH-sulfate-sulfadiazine were tested separately and in combination with pyrimethamine for the inhibitory activity on Toxoplasma gondii growth in vitro. Except for N4-acetyl-sulfadiazine, all sulfa compounds possessed anti-Toxoplasma activity. The addition of 0.05 micrograms of pyrimethamine per ml, a concentration which in itself is not inhibitory, potentiated the microbial activity of sulfadiazine and its metabolites 100 fold. PMID- 7793891 TI - Identification of a carbenicillin-hydrolyzing beta-lactamase in Alcaligenes denitrificans subsp. xylosoxydans. AB - Eleven strains of Alcaligenes denitrificans subsp. xylosoxydans produced a beta lactamase with a pI of 5.7 with kinetic data characteristic of a PSE-1-type enzyme. A CARB-type enzyme was identified by using an intragenic DNA probe of blaCARB. Hybridization of genomic DNA after XbaI restriction and pulsed-field electrophoresis suggested a chromosomal location for the gene. PMID- 7793893 TI - Efficacy of the triazole D0870 in a murine model of systemic histoplasmosis. AB - The efficacy of D0870 was studied in a murine model of systemic histoplasmosis and was compared with that of fluconazole. All regimens of D0870 (1 or 10 mg/kg of body weight given daily or 1, 10, or 100 mg/kg given every other day) and 100 mg of fluconazole per kg given daily provided complete protection from lethality. Comparison of the number of viable Histoplasma capsulatum yeasts remaining in the spleen or liver indicated that D0870 was superior to fluconazole in clearing and curing infection. D0870 was 10- to 100-fold more efficacious than fluconazole in the treatment of experimental histoplasmosis. PMID- 7793892 TI - SCH 51048, a new antifungal triazole active against hematogenous Candida krusei infections in neutropenic mice. AB - Candida krusei is increasingly recognized as an opportunistic pathogen in immunocompromised patients and is inherently resistant to fluconazole. We tested the in vivo efficacy of SCH 51048, an investigational antifungal triazole, in experimental hematogenous murine infection caused by two C. krusei isolates and compared its activity with those of amphotericin B and fluconazole. CF1 mice were immunosuppressed with cyclophosphamide and cortisone acetate and were challenged intravenously with infecting inocula of each C. krusei isolate. Treatment with SCH 51048 (50 or 100 mg/kg of body weight per day orally) or amphotericin B (2 mg/kg/day intraperitoneally) significantly prolonged the survival of infected mice and significantly reduced fungal titers in the kidneys (P < or = 0.05). Treatment with fluconazole (100 mg/kg/day orally) had no effect. Both dosages of SCH 51048 were as effective as amphotericin B in improving survival, but the higher dosage was significantly (P < or = 0.05) better in reducing the fungal burden in the kidneys of infected animals. A dose-dependent response was observed with SCH 51048 treatment, especially in organ clearance. Our results indicate that SCH 51048 is the first triazole that has in vivo activity against experimental infection with C. krusei and deserves further evaluation. PMID- 7793894 TI - Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics. AB - Antibiotics of the vancomycin group are shown to enhance their affinities for the bacterial cell wall by the devices of either dimerization (vancomycin and other glycopeptides which dimerize even more strongly) or use of a membrane anchor (teicoplanin); a chelate mechanism is suggested in both cases, as supported by antagonism experiments with the cell wall analog di-N-acetyl-L-Lys-D-Ala-D-Ala. These results may have implications for other binding processes which occur near membrane surfaces. PMID- 7793897 TI - Photosensitivity associated with ciprofloxacin use in adult patients with cystic fibrosis. PMID- 7793895 TI - Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model. AB - Rifabutin, clarithromycin, and ethambutol, which were administered at concentrations similar to those used in clinical trials that are now under way, were tested for their capacities to inhibit the growth of two highly virulent isolates of Mycobacterium avium in inbred C57BL/6 mice and in vitro in a bone marrow-derived murine macrophage model. In the latter model rifabutin and clarithromycin had modest activities against strain 101 and somewhat better activities against strain 2-151. When they were tested in vivo, however, the best results, against strain 101 were seen when the three drugs were given in combination, whereas against strain 2-151 the combination therapy showed no significant improvement over that of clarithromycin given alone. It will be of interest to note to what degree the eventual outcomes of the current trials correlate with the predictions of these animal model systems. PMID- 7793896 TI - nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa. AB - Quinolone resistance gene nqr-T91 in a clinical isolate of Pseudomonas aeruginosa P1481 was cotransducible with catA1 in P. aeruginosa PAO. The nqr-T91 transductant, PKH-T91, was resistant to norfloxacin, imipenem, and chloramphenicol and showed less norfloxacin accumulation than the parent strain did. Loss of the 46-kDa outer membrane protein (D2) and an increase in the 50-kDa outer membrane protein in PKH-T91 were observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Lipopolysaccharides in the transductant were also changed. These alterations were considered to be related to lower levels of norfloxacin accumulation in PKH-T91. These genetic and biochemical properties suggested that an nfxC type of quinolone-resistant mutation occurred in a clinical isolate of P. aeruginosa P1481. PMID- 7793898 TI - Effect of novobiocin-containing antimicrobial regimens on infection and colonization with vancomycin-resistant Enterococcus faecium. PMID- 7793899 TI - You, too, can publish an article in the AORN Journal. PMID- 7793900 TI - Angioplasty with stent placement in peripheral arterial occlusive disease. AB - Percutaneous transluminal balloon angioplasty (PTBA) is a minimally invasive and effective adjunct treatment for patients with atherosclerotic peripheral vascular disease. This surgical technique involves placing an intraarterial balloon within an obstructing arterial lesion and forcibly dilating the balloon under fluoroscopy. The PTBA technique has become an accepted interventional therapy for iliac artery stenoses. In selected patients with stenotic lesions of the iliac artery, percutaneous transluminal angioplasty (PTA) with the use of an intravascular stent may be an alternative to traditional aortofemoral bypass surgery. The PTA procedure involves only a needle entry site in one or both groins as opposed to an incision exposing the entire abdomen. The hospital stay for the average patient undergoing PTA of the iliac artery is three days as opposed to seven days for the patient undergoing aortofemoral bypass, and the patient may return to normal activity in a much shorter period of time after a PTA procedure. PMID- 7793901 TI - Perioperative nursing interventions for intravascular stent placements. AB - Keeping abreast of changing surgical technologies is among the more challenging aspects of perioperative nursing. Because peripheral vascular disease is a leading cause of lower extremity disabilities that require surgical interventions, new procedures and techniques are being developed continually. These procedures involve the insertion of intraluminal structural supports into patients who have had mixed or unsuccessful results from angioplasty. Perioperative nurses are an integral part of vascular surgery teams performing the insertion of intravascular stents. To function effectively, perioperative nurses must understand the concepts of intravascular stent procedures, nursing diagnoses, and nursing interventions that promote optimal patient outcomes. PMID- 7793902 TI - The challenge of performing three heart transplantations in one day. AB - Heart transplantation procedures, which present a number of challenges not generally seen in perioperative nursing practice, provide important knowledge for perioperative nurses because they demonstrate the importance of organization, communication, collaboration, and resourcefulness among surgical team members. On Friday, Aug 13, 1993, the Virginia Heart Center at Fairfax Hospital, Falls Church, implanted donor hearts in three adult recipients in a single day. The day was even more challenging because of elective coronary artery bypass graft procedures performed on three other patients. Successful response to the demands of Aug 13 was facilitated by the presence of skilled, versatile, cardiovascular OR staff members. PMID- 7793904 TI - Minimizing patients' hypothermia and bleeding after cardiac surgery. PMID- 7793905 TI - Developing an instrument for measuring patient satisfaction. AB - We developed a 21-item questionnaire to evaluate the effectiveness of nursing care provided in an outpatient surgery center. The four constructs of the instrument for measuring patient satisfaction are caring, continuity of care, competence of nurses, and education of patients and family members. Content validity and test-retest reliability have been established. Using this tool to analyze patients' responses to nursing care can help perioperative nurses improve patient care and patient satisfaction. PMID- 7793903 TI - Competency-based orientation for perioperative cardiovascular nurses. AB - Nurses working in cardiovascular surgery must be responsible and highly competent to meet the demands of their profession. Hospitals that hire nurses for cardiovascular surgery also must assume responsibility for the competency of nurses hired. The Virginia Heart Center at Fairfax Hospital, Falls Church, uses a competency-based orientation plan to train newly hired cardiovascular surgery nurses in providing quality care. Competency-based orientation is an effective approach to incorporating new members of the team into the work environment. The benefits of this appraoch include the development of teamwork and esprit de corps, skill and knowledge enhancement, and possible increased staff retention. PMID- 7793906 TI - State health care reform blocked by federal legislation. PMID- 7793907 TI - Biocontrol of mold growth in high-moisture wheat stored under airtight conditions by Pichia anomala, Pichia guilliermondii, and Saccharomyces cerevisiae. AB - Pichia anomala inhibits the growth of Penicillium roqueforti and Aspergillus candidus on agar. In this investigation, antagonistic activity on agar against 17 mold species was determined. The abilities of Pichia anomala, Pichia guilliermondii, and Saccharomyces cerevisiae to inhibit the growth of the mold Penicillium roqueforti in nonsterile high-moisture wheat were compared by adding 10(3) Penicillium roqueforti spores and different amounts of yeast cells per gram of wheat. Inoculated grain was packed in glass tubes, incubated at 25 degrees C with a restricted air supply, and the numbers of yeast and mold CFU were determined on selective media after 7 and 14 days. Pichia anomala reduced growth on agar plates for all of the mold species tested in a dose-dependent manner. Aspergillus fumigatus and Eurotium amstelodami were the most sensitive, while Penicillium italicum and Penicillium digitatum were the most resistant. Pichia anomala had the strongest antagonistic activity in wheat, with 10(5) and 10(6) CFU/g completely inhibiting the growth of Penicillium roqueforti. Inhibition was least pronounced at the optimum temperature (21 degrees C) and water activity (0.95) for the growth of Penicillium roqueforti. Pichia guilliermondii slightly reduced the growth of Penicillium roqueforti in wheat inoculated with 10(5) and 10(6) yeast CFU/g. S. cerevisiae inhibited mold growth only weakly at the highest inoculum level. Pichia anomala grew from 10(3) to 10(7) CFU/g of wheat in 1 week. To reach the same level, Pichia guilliermondii had to be inoculated at 10(4) CFU while S. cerevisiae required an inoculum of 10(5) CFU to reach 10(7) CFU/g of wheat. PMID- 7793909 TI - Construction and characterization of a DNA probe for distinguishing strains of Aspergillus flavus. AB - Repetitive DNA sequences have proven useful and reliable characters in evaluating genetic relatedness of strains at different levels of taxonomic classification. A DNA probe was constructed to distinguish among strains of Aspergillus flavus by DNA fingerprinting techniques. Chromosomal DNA of A. flavus var. flavus NRRL 6541 was partially digested with EcoRI and ligated to a Lambda Dash bacteriophage vector. Four lambda clones were identified which displayed multiple and distinct bands when hybridized with chromosomal DNA from seven strains of A. flavus var. flavus digested with either EcoRI or PstI. One of these clones was chosen for further analysis and was subcloned into pUC19. The subclone, pAF28, contained a 6.2-kb chromosomal DNA insert and was able to distinguish among strains characterized by K. E. Papa (Mycologia 78:98-101, 1986) as belonging to 22 different vegetative compatibility groups. The subclone identified unique banding patterns when hybridized to genomic DNA digested with PstI. The cloned probe may be species specific as it hybridized with the DNA of all isolates of A. flavus tested in addition to strains recognized as varieties of A. flavus (e.g., A. flavus var. oryzae, A. flavus var. parasiticus, and A. flavus var. sojae). pAF28 hybridized to a single band on a Southern blot with Aspergillus nomius DNA but did not hybridize with the DNA of other fungal species tested including Aspergillus ochraceus, Aspergillus auricomus, Aspergillus alliaceus, Fusarium moniliforme, and Penicillium thomii. PMID- 7793908 TI - Isolation and characterization of acidocin A and cloning of the bacteriocin gene from Lactobacillus acidophilus. AB - Acidocin A, a bacteriocin produced by Lactobacillus acidophilus TK9201, is active against closely related lactic acid bacteria and food-borne pathogens including Listeria monocytogenes. The bacteriocin was purified to homogeneity by ammonium sulfate precipitation and sequential ion-exchange and reversed-phase chromatographies. The molecular mass was determined by high-performance liquid chromatography gel filtration to be 6,500 Da. The sequence of the first 16 amino acids of the N terminus was determined, and oligonucleotide probes based on this sequence were constructed to detect the acidocin A structural gene acdA. The probes hybridized to the 4.5-kb EcoRI fragment of a 45-kb plasmid, pLA9201, present in L. acidophilus TK9201, and the hybridizing region was further localized to the 0.9-kb KpnI-XbaI fragment. Analysis of the nucleotide sequence of this fragment revealed that acidocin A was synthesized as an 81-amino-acid precursor including a 23-amino-acid N-terminal extension. An additional open reading frame (ORF2) encoding a 55-amino-acid polypeptide was found downstream of and in the same operon as acdA. Transformants containing this ORF2 became resistant to acidocin A, suggesting that ORF2 encodes an immunity function for acidocin A. The 7.2-kb SacI-XbaI fragment containing the upstream region of acdA of pLA9201 was necessary for acidocin A expression in the acidocin A-deficient mutant, L. acidophilus TK9201-1, and other Lactobacillus strains. PMID- 7793910 TI - Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3. AB - The lantibiotic nisin is produced by several strains of Lactococcus lactis. The complete gene cluster for nisin biosynthesis in L. lactis 6F3 comprises 15 kb of DNA. As described previously, the structural gene nisA is followed by the genes nisB, nisT, nisC, nisI, nisP, nisR, and nisK. Further analysis revealed three additional open reading frames, nisF, nisE, and nisG, adjacent to nisK. Approximately 1 kb downstream of the nisG gene, three open reading frames in the opposite orientation have been identified. One of the reading frames, sacR, belongs to the sucrose operon, indicating that all genes belonging to the nisin gene cluster of L. lactis 6F3 have now been identified. Proteins NisF and NisE show strong homology to members of the family of ATP-binding cassette (ABC) transporters, and nisG encodes a hydrophobic protein which might act similarly to the immunity proteins described for several colicins. Gene disruption mutants carrying mutations in the genes nisF, nisE, and nisG were still able to produce nisin. However, in comparison with the wild-type strain, these mutants were more sensitive to nisin. This indicates that besides nisI the newly identified genes are also involved in immunity to nisin. The NisF-NisE ABC transporter is homologous to an ABC transporter of Bacillus subtilis and the MbcF-MbcE transporter of Escherichia coli, which are involved in immunity to subtilin and microcin B17, respectively. PMID- 7793911 TI - Cloning and expression in Saccharomyces cerevisiae of a Trichoderma reesei beta mannanase gene containing a cellulose binding domain. AB - beta-Mannanase (endo-1,4-beta-mannanase; mannan endo-1,4-beta-mannosidase; EC 3.2.1.78) catalyzes endo-wise hydrolysis of the backbone of mannan and heteromannans, including hemicellulose polysaccharides, which are among the major components of plant cell walls. The gene man1, which encodes beta-mannanase, of the filamentous fungus Trichoderma reesei was isolated from an expression library by using antiserum raised towards the earlier-purified beta-mannanase protein. The deduced beta-mannanase consists of 410 amino acids. On the basis of hydrophobic cluster analysis, the beta-mannanase was assigned to family 5 of glycosyl hydrolases (cellulase family A). The C terminus of the beta-mannanase has strong amino acid sequence similarity to the cellulose binding domains of fungal cellulases and is preceded by a serine-, threonine-, and proline-rich region. Consequently, the beta-mannanase is probably organized similarly to the T. reesei cellulases, having a catalytic core domain separated from the substrate binding domain by an O-glycosylated linker. Active beta-mannanase was expressed and secreted by using the yeast Saccharomyces cerevisiae as the host. The results indicate that the man1 gene encodes the two beta-mannanases with different isoelectric points (pIs 4.6 and 5.4) purified earlier from T. reesei. PMID- 7793912 TI - PCR amplification and direct sequencing of gyrB genes with universal primers and their application to the detection and taxonomic analysis of Pseudomonas putida strains. AB - Degenerate PCR primers, UP-1 and UP-2r, for the amplification of DNA gyrase subunit B genes (gyrB) were designed by using consensus amino acid sequences of gyrases from Escherichia coli, Pseudomonas putida, and Bacillus subtilis. In addition to the degenerate sequences, these primers have sequences at the 5' end which allow direct sequencing of amplified PCR products. With these primers, DNA segments of the predicted size were amplified from a variety of gram-negative and gram-positive genera. The nucleotide sequences of the amplified gyrB DNA from three P. putida strains were determined directly from the amplified fragments. The base substitution frequency of gyrB between the strains of P. putida was much higher than that of the 16S rRNA gene. With a specific set of PCR primers, it was possible to amplify gyrB fragments selectively from P. putida or its subgroups. The direct sequencing method of gyrB developed in this study provides a rapid and convenient system for bacterial identification, taxonomic analysis, and monitoring of bacteria in the natural environment. PMID- 7793913 TI - Addition of cellulolytic clostridia to the bovine rumen and pig intestinal tract. AB - Studies were conducted to determine whether intestinal cellulolytic bacteria could be introduced into the bovine rumen or pig large intestine. In the first study, the ruminal fluid of three cows was evacuated and replaced with 20 liters of buffer and 6 liters of the ruminal or swine cellulolytic organism Clostridium longisporum or Clostridium herbivorans, respectively. The introduced organisms were the predominant cellulolytic bacterium in the fluid (> 10(7) cells ml-1) at 0 h. C. longisporum was still the predominant cellulolytic organism after 5 h, at 0.55 x 10(7) cells ml-1; however, after 24 h the count of C. longisporum decreased to 0.05 x 10(7) cells ml-1 compared with 2.8 x 10(7) cells ml-1 for the total cellulolytic organisms. After 48 h, C. longisporum was no longer detectable. C. herbivorans was identified in only one of the three cows after 24 h and was not detected at 72 h. In a second study, when C. longisporum (50 ml; 10(7) cells ml-1) was infused into the terminal ileum of seven pigs, it was not recovered when fecal samples were evaluated at 24, 48, or 72 h after infusion. These studies emphasize the competition that must be overcome to successfully introduce organisms into an intestinal ecosystem. Furthermore, these studies suggest that C. longisporum is a transient organism in the bovine rumen; however, C. herbivorans is part of the normal intestinal flora of some pigs, although the role that it plays in fiber degradation in these pigs is unclear. PMID- 7793914 TI - Evidence that water transmits Vibrio vulnificus biotype 2 infections to eels. AB - Vibrio vulnificus biotype 2 is classically considered an obligate eel pathogen. However, it has recently been associated with one human septicemic case. In this paper, the opportunistic behavior of this pathogen is discussed. The bacterium can survive alone in brackish water or attached to eel surfaces for at least 14 days. It is able to spread through water and infect healthy eels by using skin as a portal of entry. These results suggest that water and infected eels may act as reservoirs of infection. A capsule seems to be essential for waterborne infectivity, which would explain why cells recovered from naturally diseased eels give rise to pure cultures of opaque colonies. The spread of the disease is dependent on temperature and water salinity, thus suggesting a method to reduce the risk of epizootics and that of infection for humans. PMID- 7793915 TI - Comparison of methods of DNA extraction from stream sediments. AB - In Upper Three Runs Creek (Aiken, S.C.) and many other environments, less than 1% of bacteria visible microscopically can be cultured. Exploitation of molecular biology techniques has led to development of new methods, such as extraction of nucleic acids from soils or sediments, to study the dominant, nonculturable bacteria. The purpose of this study was to compare three published methods of DNA extraction that fall into two general categories: those in which cells are lysed in sediments (the Ogram and Tsai and methods [A. Ogram, G. S. Sayler, and T. Barkay, J. Microbiol. Methods 7:57-66, 1987; Y. L. Tsai and B. H. Olson, Appl. Environ. Microbiol. 57:1070-1074, 1991]) and those in which cells are removed from sediments prior to lysis (the Jacobsen method [C. S. Jacobsen and O. S. Rasmussen; Appl. Environ. Microbiol. 58:2458-2462, 1992]). DNA yield varied with extraction method; the Ogram method had a significantly higher yield than the other methods. However, DNA extracted via the Ogram method was badly sheared and contained a smaller proportion of eubacterial DNA. The Tsai method was less time consuming than the other methods, but DNA samples were of lower purity. If DNA purity is of paramount concern (as would be the case if PCR was to be performed) and quantity is not important, the Jacobsen method is recommended because of the low concentration of contaminants. If DNA is to be used directly in DNA-DNA hybridizations, the Ogram method is recommended since it gives maximal yields.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793916 TI - Comparison of Lactobacillus strains with respect to bile salt hydrolase activity, colonization of the gastrointestinal tract, and growth rate of the murine host. AB - The significance of bile salt hydrolase production by lactobacilli in the microecology of the murine intestinal tract has not been extensively studied previously. Assays of bile salt hydrolase (sodium taurocholate as substrate) associated with cell extracts of five Lactobacillus strains of murine origin gave a range of activities (from 915 nmol of cholate released per mg of protein per 30 min to none detected). All of the strains tested colonized the murine gastrointestinal tract equally well. The growth rates of mice were not affected by colonization of their intestinal tracts by lactobacilli whether or not the bacteria produced bile salt hydrolase. PMID- 7793917 TI - Thermostability of Ochratoxin A in wheat under two moisture conditions. AB - The decomposition of ochratoxin A (OTA) was examined, under different temperature and moisture conditions. The calculated half-lives, corresponding to 50% values, were 707, 201, 12, and 6 min, respectively, at 100, 150, 200, and 250 degrees C for dry wheat and 145, 60, and 19 min, respectively, at 100, 150, and 200 degrees C for wheat heated under wet conditions. The presence of water (50%) increased the decomposition of OTA at 100 and 150 degrees C; the opposite was observed at 200 degrees C. Complete destruction of OTA within the limits of this study (100 to 250 degrees C) was not obtained. PMID- 7793919 TI - Stabilization of microbial cytochrome P-450 activity by creation of station-phase conditions in a continuously operated immobilized-cell reactor. AB - Bacillus megaterium (ATCC 13368) exhibits cytochrome P-450 monooxygenase activity (referred to herein as Cyt P-450 meg) catalyzing 15 beta-steroid hydroxylation. This activity belongs to the widespread ferredoxin reductase-ferredoxin-Cyt P-450 type of monooxygenases, providing a representative model system for this type of activity. The level of Cyt P-450 meg activity reaches its maximum in the cells during the stationary phase of the growth curve and is not affected by Cyt P-450 inducers. Here we present the development of an approach for stabilizing the Cyt P-450 meg system so that it performs continuous steroid hydroxylation and will be a model system for Cyt P-450-based detoxification. It is based on cell immobilization and simulation of stationary-phase conditions in a continuously operated fluidized-bed bioreactor. The combination of an appropriate immobilization technique, operational conditions, and medium composition provided a stabilized cell environment resulting in "freezing" of a physiological steady state analog under stationary phase conditions, allowing stable performance of continuous hydroxylation for several weeks. It is suggested that this approach may be extended for use with other environmentally induced enzymatic activities. PMID- 7793918 TI - Multiple Vibrio vulnificus strains in oysters as demonstrated by clamped homogeneous electric field gel electrophoresis. AB - Clamped homogeneous electric field gel electrophoresis and a computer program for managing electrophoresis banding patterns (ELBAMAP) were used to analyze genomic DNA of 118 Vibrio vulnificus strains, isolated from three oysters by direct plating. Analysis with SfiI resulted in 60 restriction endonuclease digestion profiles (REDP), while analysis with SrfI produced 53 different REDP. Similarities between REDP ranged from 7 to 93%. Principal-component analysis showed that the strains were heterogeneous. PMID- 7793920 TI - Regulation of the alginate biosynthesis gene algC in Pseudomonas aeruginosa during biofilm development in continuous culture. AB - Reporter gene technology was used to observe the regulation of the alginate biosynthesis gene, algC in a mucoid strain of Pseudomonas aeruginosa in developing and mature biofilms in continuous culture on Teflon and glass substrata. The plasmid pNZ63, carrying an algC-lacZ transcriptional fusion, was shown to not be diluted in continuous culture over a period of 25 days in the absence of selection pressure. Biofilm cells under bulk phase steady-state conditions demonstrated fluctuations in algC expression over a 16-day period, but no trend of increased or decreased expression over the time interval was indicated. In vivo detection of algC up-expression in developing biofilms was performed with a fluorogenic substrate for the plasmid-borne lacZ gene product (beta-galactosidase) by using microscopy coupled with image analysis. By this technique, cells were tracked over time and analyzed for algC activity. During the initial stages of biofilm development, cells already attached to a glass surface for at least 15 min exhibited up-expression of algC, detectable as the development of whole-cell fluorescence. However, initial cell attachment to the substratum appeared to be independent of algC promoter activity. Furthermore, cells not exhibiting algC up-expression were shown to be less capable of remaining at a glass surface under flowing conditions than were cells in which algC up-expression was detected. PMID- 7793921 TI - Laccase component of the Ceriporiopsis subvermispora lignin-degrading system. AB - Laccase activity in the lignin-degrading fungus Ceriporiopsis subvermispora was associated with several proteins in the broth of cultures grown in a defined medium. Activity was not increased significantly by adding 2,5-xylidine or supplemental copper to the medium. Higher activity, associated with two major isoenzymes, developed in cultures grown on a wheat bran medium. These two isoenzymes were purified to homogeneity. L1 and L2 had isoelectric points of 3.4 and 4.8, molecular masses of 71 and 68 kDa, and approximate carbohydrate contents of 15 and 10%, respectively. Data indicated 4 copper atoms per mol. L1 and L2 had overlapping pH optima in the range of 3 to 5, depending on the substrate, and exhibited half-lives of 120 and 50 min at 60 degrees C. They were strongly inhibited by sodium azide and thioglycolic acid but not by hydroxylamine or EDTA. The isoenzymes oxidized 1,2,4,5-tetramethoxybenzene but not other methoxybenzene congeners. A variety of usual laccase substrates, including lignin-related phenols and ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)], were also oxidized. Kinetic parameters were similar to those of the laccases of Coriolus versicolor. The N-terminal amino acid sequence (20 residues for L1) showed significant homology to those of laccases of other white rot basidiomycetes but not to those of the laccases of Agaricus bisporus or Neurospora crassa. PMID- 7793922 TI - Denitrification by the fungus Cylindrocarpon tonkinense: anaerobic cell growth and two isozyme forms of cytochrome P-450nor. AB - We examined the denitrification system of the fungus Cylindrocapon tonkinense and found several properties distinct from those of the denitrification system of Fusarium oxysporum. C. tonkinense could form N2O from nitrite under restricted aeration but could not reduce nitrate by dissimilatory metabolism. Nitrite dependent N2O formation and/or cell growth during the anaerobic culture was not affected by further addition of ammonium ions but was suppressed by respiration inhibitors such as rotenone or antimycin, suggesting that denitrification plays a physiological role in respiration. Dissimilatory nitrite reductase and nitric oxide reductase (Nor) activities could not be detected in cell extracts of the denitrifying cells. The Nor activity was purified and found to depend upon two isoenzymes of Cytochrome P-450nor (P-450nor), which were designated P-450nor1 and P-450nor2. These isozymes differed in the N-terminal amino acid sequence, isoelectric point, specificity to the reduced pyridine nucleotide (NADH or NADPH), and the reactivity to the antibody to P-450nor of F. oxysporum. the difference between the specificities to NADH and NADPH suggests that P-450nor1 and P-450nor2 play different roles in anaerobic energy acquisition. PMID- 7793923 TI - Activity of synchronized cells of a steady-state biofilm recirculated reactor during xenobiotic biodegradation. AB - The maintenance of a steady-state biofilm in a continuous-flow fixed-bed reactor, as a consequence of the reproduction-detachment of cells (an interfacial cell physiology phenomenon of steady-state biofilm) during the biodegradation of 2,4,6 trichlorophenol by Pseudomonas cells, was determined. After cell adhesion on an open-pore glass support, the biofilm was formed in a packed-bed recirculated reactor. After the steady-state biofilm was reached, the mechanisms of the interfacial cell detachment (at the biofilm-liquid interface) were determined. It was established that (i) the hydrophobicity of immobilized sessile cells (parent cells) increased (from 50 to 80%) as the dilution rate increased, while the hydrophobicity of detached suspended cells (daughter cells) remained constant (about 45%); and (ii) the immediately detached suspended cells showed a synchronized growth in about three generations. These results indicate that (i) the immobilized sessile and suspended detached cells grew synchronically at the end and at the beginning of the cell cycle, respectively; and (ii) the hydrophobicity difference of immobilized sessile and suspended detached cells permitted the cells detachment. Therefore, it is probable that independent of shear stress (due to recirculated flow), the synchronized growth and hydrophobicity of cells (which vary during the cell cycle) are the main factors permitting the maintenance of a steady-state xenobiotic-degrading biofilm reactor (in which the overall accumulation of biofilm is determined by the average growth rate of the biofilm cells minus the rate of detachment of cells from the biofilm). PMID- 7793924 TI - Isolation and characterization of a cytotoxic metabolite of Talaromyces bacillosporus. AB - A cytotoxic metabolite, talarotoxin, was isolated from a fungus, Talaromyces bacillosporus IFO 8397, cultured on rice. The structure of the toxin was elucidated and found to contain a pyrrolizidinedione connected with a trans delta 1-octalin through a conjugated triene. PMID- 7793925 TI - Characterization and substrate specificity of an endo-beta-1,4-D-glucanase I (Avicelase I) from an extracellular multienzyme complex of Bacillus circulans. AB - An endo-1,4-beta-D-glucanase I (Avicelase I; EC 3.2.1.4) was purified to homogeneity from an extracellular celluloxylanosome of Bacillus circulans F-2. The purification in the presence of 6 M urea yielded homogeneous enzyme. The enzyme had a monomeric structure, its relative molecular mass being 75 kDa as determined by gel filtration and 82 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The pI was 5.4, and the N-terminal amino acid sequence was ASNIGGWVGGNESGFEFG. The optimal pH was 4.5, and the enzyme was stable at pH 4 to 10. The enzyme has a temperature optimum of 50 degrees C, it was stable at 55 degrees C for 46 h, and it retains approximately 20% of its activity after 30 min at 80 degrees C. It showed high-level activity towards carboxymethyl cellulose (CMC) as well as p-nitrophenyl-beta-D-cellobioside, 4 methylumbelliferyl cellobioside, xylan, Avicel, filter paper, and some cello oligosaccharides. Km values for birch xylan, CMC, and Avicel were 4.8, 7.2, and 87.0 mg/ml, respectively, while Vmax values were 256, 210, and 8.6 mumol x min-1 x mg-1, respectively. Cellotetraose was preferentially cleaved into cellobiose (G2) plus G2, and cellopentaose was cleaved into G2 plus cellotriose (G3), while cellohexaose was cleaved into cellotetraose plus G2 and to a lesser extent G3 plus G3. G3 was not cleaved at all. G2 was the main product of Avicel hydrolysis. Xylotetraose (X4) and xylobiose (X2) were mainly produced by the enzyme hydrolysis of xylan. G2 inhibited the activity of carboxymethyl cellulase and Avicelase, whereas Mg2+ stimulated it. The enzyme was completely inactivated by Hg2+, and it was inhibited by a thiol-blocking reagent. Hydrolysis of CMC took place, with a rapid decrease in viscosity but a slow liberation of reducing sugars. On the basis of these results, it appeared that the cellulase should be regarded as endo-type cellulase, although it hydrolyzed Avicel. PMID- 7793926 TI - Development and testing of improved suicide functions for biological containment of bacteria. AB - We have developed very efficient suicide functions for biological containment based on the lethal Escherichia coli relF gene. The suicide functions are placed in duplicate within a plasmid and arranged to prevent inactivation by deletion, recombination, and insertional inactivation. The efficiency of this concept was tested in a plasmid containment system that prevents transfer of plasmids to wild type bacteria. Protection against plasmid transfer was assayed in test tubes and in rat intestine. Protection was efficient and refractory to inactivation by mutation and transposons. The efficiency of the suicide system was also tested in soil and seawater. We show that unprecedented suicide efficiency can be achieved in soil and seawater after suicide induction by IPTG (isopropyl-beta-D thiogalactopyranoside). More than 7 orders of magnitude reduction in suicide bacteria was achieved. PMID- 7793927 TI - Suppression of Listeria monocytogenes colonization following adsorption of nisin onto silica surfaces. AB - Nisin is an antimicrobial peptide proven to be an effective inhibitor of gram positive bacteria. It is known that nisin can adsorb to various surfaces and still retain much of its original activity (M. A. Daeschel, J. McGuire, and H. Al Makhlafi, J. Food Prot. 55:731-735, 1992). In this study, nisin films were allowed to form on silanized silica surfaces and then exposed to medium containing Listeria monocytogenes. Representative areas were selected from each surface, and images of resident listeriae were obtained at 4-h intervals for 12 h. During this time, cells on surfaces that had been in contact with a high concentration of nisin (1.0 mg/ml) exhibited no signs of growth and many displayed evidence of cellular deterioration. Surfaces treated with a lower concentration of nisin (0.1 mg/ml) had a smaller degree of inhibition. In contrast, both protein-free surfaces and those with films of heat-inactivated nisin allowed attached L. monocytogenes cells to grow and reproduce. These studies, when repeated with a nisin-resistant strain of L. monocytogenes, resulted in no inhibition of growth on surfaces with adsorbed nisin. The bactericidal effect of adsorbed nisin was also studied with iodonitrotetrazolium violet, a tetrazolium salt, which is reduced to a red formazan crystal by viable bacteria. Crystals were visible in 95% of the cells adhered to control surfaces but were present in less than 20% of the cells on surfaces with adsorbed nisin. These data indicate that adsorbed nisin may have potential for use as a food grade antimicrobial agent on food contact surfaces. PMID- 7793929 TI - Characterization of biphenyl catabolic genes of gram-positive polychlorinated biphenyl degrader Rhodococcus sp. strain RHA1. AB - Rhodococcus sp. strain RHA1 is a gram-positive polychlorinated biphenyl (PCB) degrader which can degrade 10 ppm of PCB48 (equivalent to Aroclor1248), including tri-, tetra-, and pentachlorobiphenyls, in a few days. We isolated the 7.6-kb EcoRI-BamHI fragment carrying the biphenyl catabolic genes of RHA1 and determined their nucleotide sequence. On the basis of deduced amino acid sequence homology, we identified six bph genes, bphA1A2A3A4, bphB, and bphC, that are responsible for the initial three steps of biphenyl degradation. The order of bph genes in RHA1 is bphA1A2A3A4-bphC-bphB. This gene order differs from that of other PCB degraders reported previously. The amino acid sequences deduced from the RHA1 bph genes have a higher degree of homology with the tod genes from Pseudomonas putida F1 (49 to 79%) than with the bph genes of Pseudomonas sp. strains KF707 and KKS102 (30 to 65%). In Escherichia coli, bphA gene activity was not observed even when expression vectors were used. The activities of bphB and bphC, however, were confirmed by observing the transformation of biphenyl to a meta-cleavage compound with the aid of benzene dioxygenase activity that complemented the bphA gene activity (S. Irie, S. Doi, T. Yorifuji, M. Takagi, and K. Yano, J. Bacteriol. 169:5174-5179, 1987). The expected products of the cloned bph genes, except bphA3, were observed in E. coli in an in vitro transcription-translation system. Insertion mutations of bphA1 and bphC of Rhodococcus sp. strain RHA1 were constructed by gene replacement with cloned gene fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793930 TI - Detection and counting of Nitrobacter populations in soil by PCR. AB - Although the biological conversion of nitrite to nitrate is a well-known process, studies of Nitrobacter populations are hindered by their physiological characteristics. This report describes a new method for detecting and counting Nitrobacter populations in situ with the PCR. Two primers from the 16S rRNA gene were used to generate a 397-bp fragment by amplification of Nitrobacter species DNA. No signal was detected from their phylogenetic neighbors or the common soil bacteria tested. Extraction and purification steps were optimized for minimal loss and maximal purity of soil DNA. The detection threshold and accuracy of the molecular method were determined from soil inoculated with 10, 10(2), or 10(3) Nitrobacter hamburgensis cells per g of soil. Counts were also done by the most probable-number (MPN)-Griess and fluorescent antibody methods. PCR had a lower detection threshold (10(2) Nitrobacter cells per g of soil) than did the MPN Griess or fluorescent antibody method. When PCR amplification was coupled with the MPN method, the counting rate reached 65 to 72% of inoculated Nitrobacter cells. Tested on nonsterile soil, this rapid procedure was proved efficient. PMID- 7793928 TI - Identification and epidemiological typing of Naegleria fowleri with DNA probes. AB - Naegleria fowleri is a small free-living amoeboflagellate found in warm water habitats worldwide. The organism is pathogenic to humans, causing fatal primary amoebic meningoencephalitis. When monitoring the environment for the presence of N. fowleri, it is important to reliably differentiate the organism from other closely related but nonpathogenic species. To this end, we have developed species specific DNA probes for use in the rapid identification of N. fowleri from the environment. Samples were taken from the thermal springs in Bath, England, and cultured for amoebae. Of 84 isolates of thermophilic Naegleria spp., 10 were identified as N. fowleri by probe hybridization. The identity of these isolates was subsequently confirmed by their specific whole-cell DNA restriction fragment length polymorphisms (RFLPs). One DNA clone was found to contain a repeated element that detected chromosomal RFLPs that were not directly visible on agarose gels. This enabled the further differentiation of strains within geographically defined whole-cell DNA RFLP groups. N. fowleri DNA probes represent a specific and potentially rapid method for the identification of the organism soon after primary isolation from the environment. PMID- 7793931 TI - Phenotypic and genetic diversity of chlorine-resistant Methylobacterium strains isolated from various environments. AB - Strains of pink-pigmented facultative methylotrophs which were isolated previously from various environments and assigned tentatively to the genus Methylobacterium were characterized in comparison with authentic strains of previously known species of this genus. Most of the isolates derived from chlorinated water supplies exhibited resistance to chlorine, whereas 29 to 40% of the isolates from air, natural aquatic environments, and clinical materials were chlorine resistant. None of the tested authentic strains of Methylobacterium species obtained from culture collections exhibited chlorine resistance. Numerical analysis of phenotypic profiles showed that the test organisms tested were separated from each other except M. organophilum and M. rhodesianum. The chlorine-resistant isolates were randomly distributed among all clusters. The 16S ribosomal DNA (rDNA) sequence-based phylogenetic analyses showed that representatives of the isolates together with known Methylobacterium species formed a line of descent distinct from that of members of related genera in the alpha-2 subclass of the Proteobacteria and were divided into three subclusters within the Methylobacterium group. These results demonstrate that there is phenotypic and genetic diversity among chlorine-resistant Methylobacterium strains within the genus. PMID- 7793932 TI - Characterization of genetically transformed Saccharomyces cerevisiae baker's yeasts able to metabolize melibiose. AB - Three transformant (Mel+) Saccharomyces cerevisiae baker's yeast strains, CT-Mel, VS-Mel, and DADI-Mel, have been characterized. The strains, which originally lacked alpha-galactosidase activity (Mel-), had been transformed with a DNA fragment which possessed an ILV1-SMR1 allele of the ILV2 gene and a MEL1 gene. The three transformed strains showed growth rates similar to those of the untransformed controls in both minimal and semi-industrial (molasses) media. The alpha-galactosidase specific activity of strain CT-Mel was twice that of VS-Mel and DADI-Mel. The yield, YX/S (milligrams of protein per milligram of substrate), in minimal medium with raffinose as the carbon source was 2.5 times higher in the transformed strains than in the controls and was 1.5 times higher in CT-Mel than in VS-Mel and DADI-Mel. When molasses was used, YX/S (milligrams of protein per milliliter of culture) increased 8% when the transformed strains CT-Mel and DADI Mel were used instead of the controls. Whereas no viable spores were recovered from either DADI-Mel or VS-Mel tetrads, genetic analysis carried out with CT-Mel indicated that the MEL1 gene has been integrated in two of three homologous loci. Analysis of the DNA content by flow cytometry indicated that strain CT-Mel was 3n, whereas VS-Mel was 2n and DADI-Mel was 1.5n. Electrophoretic karyotype and Southern blot analyses of the transformed strains showed that the MEL1 gene has been integrated in the same chromosomic band, probably chromosome XIII, in the three strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793934 TI - Fate of Salmonella montevideo on and in raw tomatoes as affected by temperature and treatment with chlorine. AB - A study was undertaken to determine the survival patterns of Salmonella montevideo G4639 on and in tomatoes during storage and the efficacy of chlorine treatment on inactivation of the pathogen. The population of S. montevideo on the surfaces of inoculated tomatoes stored at 10 degrees C did not change significantly (P < 0.05) throughout an 18-day storage period. Significant increases in population occurred within 7 days and within 1 day when tomatoes were stored at 20 and 30 degrees C, respectively. A significantly higher number of cells was taken up by the core tissue of tomatoes tempered at 25 degrees C when the tomatoes were dipped in a suspension at 10 degrees C compared with the number taken up when the tomatoes were dipped in cell suspensions tempered at 25 or 37 degrees C. Populations remained constant throughout subsequent storage for 8 days at 10 degrees C, regardless of the temperature differential between tomatoes and the dip suspension. Storage of tomatoes at 20 degrees C, however, resulted in significant increases in populations of S. montevideo. Populations of the pathogen on the surfaces and in the core tissues of tomatoes were significantly reduced by dipping for 2 min in a solution containing 60 or 110 ppm (60 or 110 micrograms/ml) chlorine, respectively; however, treatment in solution containing 320 ppm chlorine did not result in complete inactivation. Populations of S. montevideo remained unchanged in chopped tomatoes stored at 5 degrees C for 216 h (9 days) but increased significantly after storage for 96 or 22 h at 20 or 30 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793933 TI - Quantitation of fungal mRNAs in complex substrates by reverse transcription PCR and its application to Phanerochaete chrysosporium-colonized soil. AB - Thorough analysis of fungi in complex substrates has been hampered by inadequate experimental tools for assessing physiological activity and estimating biomass. We report a method for the quantitative assessment of specific fungal mRNAs in soil. The method was applied to complex gene families of Phanerochaete chrysosporium, a white-rot fungus widely used in studies of organopollutant degradation. Among the genes implicated in pollutant degradation, two closely related lignin peroxidase transcripts were detected in soil. The pattern of lignin peroxidase gene expression was unexpected; certain transcripts abundant in defined cultures were not detected in soil cultures. Transcripts encoding cellobiohydrolases and beta-tubulin were also detected. The method will aid in defining the roles of specific genes in complex biological processes such as organopollutant degradation, developing strategies for strain improvement, and identifying specific fungi in environmental samples. PMID- 7793936 TI - Characterization of Listeria monocytogenes isolated from poultry products and from the poultry-processing environment by random amplification of polymorphic DNA and multilocus enzyme electrophoresis. AB - A total of 289 Listeria monocytogenes strains isolated from a poultry-processing environment and poultry products over a 6-month period were characterized by random amplification of polymorphic DNA, (RAPD) to pinpoint sources of contamination within the plant and gain some measure of the persistence of individual genotypes within this environment. Eighteen RAPD profiles (A through R) were identified within this group, with 64% (184 of 289) of all strains displaying a single RAPD profile, RAPD type A. This genotype was more prevalent in the raw-poultry-processing environment, where, although its origin within this environment appeared to be the incoming birds, it was also widespread on food contact surfaces, floors, and drains. This was the only genotype which persisted throughout the entire 6-month period, and it and RAPD type B were the only two genotypes found in both the raw- and cooked-poultry-processing environments. L. monocytogenes strains isolated from cooked poultry products and the cooked poultry-processing environment up to 1 year later (17 strains) contained only RAPD types A and B, highlighting the potential which exists for persistent strains to cross-contaminate foods processed in that environment. The other genotypes (C through R) occurred more sporadically, suggesting varied sources of contamination. These were confined to either the raw- or the cooked-poultry processing environment and were relatively short-lived. Further characterization of a selection of RAPD type A strains, together with strains of RAPD types B through R, was carried out by multilocus enzyme electrophoresis. Strains of RAPD type A contained two electrophoretic types, one of which was serotype 1/2a and the other was 1/2c.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793935 TI - Fe(III) and S0 reduction by Pelobacter carbinolicus. AB - There is a close phylogenetic relationship between Pelobacter species and members of the genera Desulfuromonas and Geobacter, and yet there has been a perplexing lack of physiological similarities. Pelobacter species have been considered to have a fermentative metabolism. In contrast, Desulfuromonas and Geobacter species have a respiratory metabolism with Fe(III) serving as the common terminal electron acceptor in all species. However, the ability of Pelobacter species to reduce Fe(III) had not been previously evaluated. When a culture of Pelobacter carbinolicus that had grown by fermentation of 2,3-butanediol was inoculated into the same medium supplemented with Fe(III), the Fe(III) was reduced. There was less accumulation of ethanol and more production of acetate in the presence of Fe(III). P. carbinolicus grew with ethanol as the sole electron donor and Fe(III) as the sole electron acceptor. Ethanol was metabolized to acetate. Growth was also possible on Fe(III) with the oxidation of propanol to propionate or butanol to butyrate if acetate was provided as a carbon source. P. carbinolicus appears capable of conserving energy to support growth from Fe(III) respiration as it also grew with H2 or formate as the electron donor and Fe(III) as the electron acceptor. Once adapted to Fe(III) reduction, P. carbinolicus could also grow on ethanol or H2 with S0 as the electron acceptor. P. carbinolicus did not contain detectable concentrations of the c-type cytochromes that previous studies have suggested are involved in electron transport to Fe(III) in other organisms that conserve energy to support growth from Fe(III) reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793938 TI - Copper as a signal for alginate synthesis in Pseudomonas syringae pv. syringae. AB - Plant-associated pseudomonads are commonly exposed to copper bactericides, which are applied to reduce the disease incidence caused by these bacteria. Consequently, many of these bacteria have acquired resistance or tolerance to copper salts. We recently conducted a survey of 37 copper-resistant (Cur) Pseudomonas spp., including P. cepacia, P. fluorescens, P. syringae, and P. viridiflava, and found that a subset of the P. syringae strains showed a dramatic increase in exopolysaccharide (EPS) production on mannitol-glutamate medium containing CuSO4 at 250 micrograms/ml. A modified carbazole assay indicated that the EPS produced on copper-amended media contained high levels of uronic acids, suggesting that the EPS was primarily alginic acid. Uronic acids extracted from selected strains were further confirmed to be alginate by demonstrating their sensitivity to alginate lyase and by descending paper chromatography following acid hydrolysis. Subinhibitory levels of arsenate, cobalt, lithium, rubidium, molybdenum, and mercury did not induce EPS production, indicating that alginate biosynthesis is not induced in P. syringae cells exposed to these heavy metals. A 200-kb plasmid designated pPSR12 conferred a stably mucoid phenotype to several P. syringae recipients and also increased their resistance to cobalt and arsenate. A cosmid clone constructed from pPSR12 which conferred a stably mucoid phenotype to several P. syringae strains but not to Pseudomonas aeruginosa was obtained. Results obtained in this study indicate that some of the signals and regulatory genes for alginate production in P. syringae differ from those described for alginate production in P. aeruginosa. PMID- 7793939 TI - Cloning and sequencing of LlaDCHI [corrected] restriction/modification genes from Lactococcus lactis and relatedness of this system to the Streptococcus pneumoniae DpnII system. AB - The natural 7.8-kb plasmid pSRQ700 was isolated from Lactococcus lactis subsp. cremoris DCH-4. It encodes a restriction/modification system named LlaDCHI [corrected]. When introduced into a phage-sensitive L. lactis strain, pSRQ700 confers strong phage resistance against the three most common lactococcal phage species, namely, 936, c2, and P335. The LlaDCHI [corrected] endonuclease was purified and found to cleave the palindromic sequence 5'-GATC-3'. It is an isoschizomer of Streptococcus pneumoniae DpnII. The plasmid pSRQ700 was mapped, and the genetic organization of LlaDCHI [corrected] was localized. Cloning and sequencing of the entire LlaDCHI [corrected] system allowed the identification of three open reading frames. The three genes (llaIIA, llaIIB, and llaIIC) overlapped and are under one putative promoter. A putative terminator was found at the end of llaIIC. The genes llaIIA and llaIIB coded for m6A methyltransferases, and llaIIC coded for an endonuclease. The LlaDCHI [corrected] system shares strong genetic similarities with the DpnII system. The deduced amino acid sequence of M.LlaIIA was 75% identical with that of M.DpnII, whereas M.LlaIIB was 88% identical with M.DpnA. However, R.LlalII shared only 31% identity with R.DpnII. PMID- 7793937 TI - Bacteria obtained from a sequencing batch reactor that are capable of growth on dehydroabietic acid. AB - Eleven isolates capable of growth on the resin acid dehydroabietic acid (DhA) were obtained from a sequencing batch reactor designed to treat a high-strength process stream from a paper mill. The isolates belonged to two groups, represented by strains DhA-33 and DhA-35, which were characterized. In the bioreactor, bacteria like DhA-35 were more abundant than those like DhA-33. The population in the bioreactor of organisms capable of growth on DhA was estimated to be 1.1 x 10(6) propagules per ml, based on a most-probable-number determination. Analysis of small-subunit rRNA partial sequences indicated that DhA-33 was most closely related to Sphingomonas yanoikuyae (Sab = 0.875) and that DhA-35 was most closely related to Zoogloea ramigera (Sab = 0.849). Both isolates additionally grew on other abietanes, i.e., abietic and palustric acids, but not on the pimaranes, pimaric and isopimaric acids. For DhA-33 and DhA-35 with DhA as the sole organic substrate, doubling times were 2.7 and 2.2 h, respectively, and growth yields were 0.30 and 0.25 g of protein per g of DhA, respectively. Glucose as a cosubstrate stimulated growth of DhA-33 on DhA and stimulated DhA degradation by the culture. Pyruvate as a cosubstrate did not stimulate growth of DhA-35 on DhA and reduced the specific rate of DhA degradation of the culture. DhA induced DhA and abietic acid degradation activities in both strains, and these activities were heat labile. Cell suspensions of both strains consumed DhA at a rate of 6 mumol mg of protein-1 h-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793940 TI - Genetic diversity of Desulfovibrio spp. in environmental samples analyzed by denaturing gradient gel electrophoresis of [NiFe] hydrogenase gene fragments. AB - The genetic diversity of Desulfovibrio species in environmental samples was determined by denaturing gradient gel electrophoresis (DGGE) of PCR-amplified [NiFe] hydrogenase gene fragments. Five different PCR primers were designed after comparative analysis of [NiFe] hydrogenase gene sequences from three Desulfovibrio species. These primers were tested in different combinations on the genomic DNAs of a variety of hydrogenase-containing and hydrogenase-lacking bacteria. One primer pair was found to be specific for Desulfovibrio species only, while the others gave positive results with other bacteria also. By using this specific primer pair, we were able to amplify the [NiFe] hydrogenase genes of DNAs isolated from environmental samples and to detect the presence of Desulfovibrio species in these samples. However, only after DGGE analysis of these PCR products could the number of different Desulfovibrio species within the samples be determined. DGGE analysis of PCR products from different bioreactors demonstrated up to two bands, while at least five distinguishable bands were detected in a microbial mat sample. Because these bands most likely represent as many Desulfovibrio species present in these samples, we conclude that the genetic diversity of Desulfovibrio species in the natural microbial mat is far greater than that in the experimental bioreactors. PMID- 7793943 TI - Occurrence of fecal indicator bacteria in surface waters and the subsurface aquifer in Key Largo, Florida. AB - Sewage waste disposal facilities in the Florida Keys include septic tanks and individual package plants in place of municipal collection facilities in most locations. In Key Largo, both facilities discharge into the extremely porous Key Largo limestone. To determine whether there was potential contamination of the subsurface aquifer and nearby coastal surface waters by such waste disposal practices, we examined the presence of microbial indicators commonly found in sewage (fecal coliforms, Clostridium perfringens, and enterococci) and aquatic microbial parameters (viral direct counts, bacterial direct counts, chlorophyll a, and marine vibriophage) in injection well effluent, monitoring wells that followed a transect from onshore to offshore, and surface waters above these wells in two separate locations in Key Largo in August 1993 and March 1994. Effluent and waters from onshore shallow monitoring wells (1.8- to 3.7-m depth) contained two or all three of the fecal indicators in all three samples taken, whereas deeper wells (10.7- to 12.2-m depth) at these same sites contained few or none. The presence of fecal indicators was found in two of five nearshore wells (i.e., those that were < or = 1.8 miles [< or = 2.9 km] from shore), whereas offshore wells (> or = 2.1 to 5.7 miles [< or = 3.4 to 9.2 km] from shore) showed little sign of contamination. Indicators were also found in surface waters in a canal in Key Largo and in offshore surface waters in March but not in August. Collectively, these results suggest that fecal contamination of the shallow onshore aquifer, parts of the nearshore aquifer, and certain surface waters has occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793942 TI - Gene cloning, nucleotide sequence, and expression of a cephalosporin-C deacetylase from Bacillus subtilis. AB - The gene encoding a cephalosporin-C deacetylase (CAH) from Bacillus subtilis SHS 0133 was cloned and sequenced. The nucleotide sequence contained an open reading frame encoding a polypeptide consisting of 318 amino acids, the molecular weight of which was in good agreement with the value obtained by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The deduced amino acid sequence contained the common sequence Gly-X-Ser-X-Gly found in many esterases, lipases, and serine proteases. This indicates that CAH is a serine enzyme. A possible promoter sequence which is very similar to the consensus sequences of -35 and -10 regions recognized by B. subtilis RNA polymerase utilizing sigma factor H was found in the 5'-flanking region of the CAH structural gene. Two repeated A+T-rich blocks consisting of 24 bp were also found in the upstream region of the initiation codon. We constructed a series of expression plasmids by inserting the CAH gene into Escherichia coli ATG vectors. The degree of CAH gene expression depended on promoters and vector plasmids, which have different replication origins. The expressed CAH protein was an active form in the soluble fraction obtained after cell disruption. The highest expression level was accomplished with an expression plasmid, pCAH400, which has the trp promoter and the replication origin derived from pAT153. In the fermentation using a 30-liter jar fermentor, the transformant E. coli JM103(pCAH400) produced 440 U of CAH per ml of culture during a 24-h incubation. This value corresponded to 2.1 g of CAH protein in 1 liter of culture broth. PMID- 7793941 TI - Combination of the tod and the tol pathways in redesigning a metabolic route of Pseudomonas putida for the mineralization of a benzene, toluene, and p-xylene mixture. AB - Construction of a hybrid strain which is capable of mineralizing components of a benzene, toluene, and p-xylene mixture simultaneously was attempted by redesigning the metabolic pathway of Pseudomonas putida. Genetic and biochemical analyses of the tod and the tol pathways revealed that dihydrodiols formed from benzene, toluene, and p-xylene by toluene dioxygenase in the tod pathway could be channeled into the tol pathway by the action of cis-p-toluate-dihydrodiol dehydrogenase, leading to complete mineralization of a benzene, toluene, and p xylene mixture. Consequently, a hybrid strain was constructed by cloning todC1C2BA genes encoding toluene dioxygenase on RSF1010 and introducing the resulting plasmid into P. putida mt-2. The hybrid strain of P. putida TB105 was found to mineralize a benzene, toluene, and p-xylene mixture without accumulation of any metabolic intermediate. PMID- 7793944 TI - Investigations related to the epidemic strain involved in the French listeriosis outbreak in 1992. AB - Two hundred seventy-nine cases of human listeriosis (92 pregnancy-related cases and 187 non-pregnancy-related cases) caused by a serovar 4b and phagovar 2389:2425:3274:2671:47:108:340 strain were identified in France between March and December 1992. Epidemiological investigations included a case-control study (not described here) and microbiological analyses of foods. Results of the case control study and characterization of food isolates identified pork tongue in jelly, a ready-to-eat meat product, as the major vehicle of this outbreak, and to a lesser extent, delicatessen products contaminated secondarily during handling in food stores. As far as serotyping, phage typing, DNA macrorestriction pattern analysis (obtained by pulsed-field gel electrophoresis [PFGE]), and ribotyping are concerned, this epidemic strain is phenotypically and genomically closely related to strains responsible for major outbreaks of listeriosis previously observed in Europe and North America. The epidemic strain sensu stricto as defined by PFGE (2/1/3) displayed the same serovar, phagovar, ribovar, and ApaI and NotI PFGE patterns as the epidemic strains from outbreaks in Switzerland, California, and Denmark, but it consistently showed differences in the SmaI PFGE profile. This information greatly contributed to the identification of the major food vehicle (pork tongue in jelly) and further allowed exclusion of other foods (cheese) as possible sources of this major listeriosis epidemic. PMID- 7793945 TI - Nonuniform spatial patterns of respiratory activity within biofilms during disinfection. AB - Fluorescent stains in conjunction with cryoembedding and image analysis were applied to demonstrate spatial gradients in respiratory activity within bacterial biofilms during disinfection with monochloramine. Biofilms of Klebsiella pneumoniae and Pseudomonas aeruginosa grown together on stainless steel surfaces in continuous-flow annular reactors were treated with 2 mg of monochloramine per liter (influent concentration) for 2 h. Relatively little biofilm removal occurred as evidenced by total cell direct counts. Plate counts (of both species summed) indicated an average 1.3-log decrease after exposure to 2 mg of monochloramine per liter. The fluorogenic redox indicator 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and the DNA stain 4',6-diamidino-2-phenylindole (DAPI) were used to differentiate respiring and nonrespiring cells in biofilms. Epifluorescence micrographs of frozen biofilm cross sections clearly revealed gradients of respiratory activity within biofilms in response to monochloramine treatment. These gradients in specific respiratory activity were quantified by calculating the ratio of CTC and DAPI intensities measured by image analysis. Cells near the biofilm-bulk fluid interface lost respiratory activity first. After 2 h of biocide treatment, greater respiratory activity persisted deep in the biofilm than near the biofilm-bulk fluid interface. PMID- 7793946 TI - Identification of grass-associated and toluene-degrading diazotrophs, Azoarcus spp., by analyses of partial 16S ribosomal DNA sequences. AB - The genus Azoarcus includes nitrogen-fixing, grass-associated strains as well as denitrying toluene degraders. In order to identify and group members of the genus Azoarcus, phylogenetic analysis based on partial sequences of 16S rRNA genes (16S rDNAs) is proposed. 16S rRNA-targeted PCR using specific primers to exclude amplification in the majority of other members of the beta subclass of the class Proteobacteria was combined with direct sequencing of the PCR products. Tree inference from comparisons of 446-bp rDNA fragments yielded similar results for the three known Azoarcus spp. sequences and for analysis of the complete 16S rDNA sequence. These three species formed a phylogenetically coherent group with representatives of two other Azoarcus species which were subjected to 16S rRNA sequencing in this study. This group was related to Rhodocyclus purpureus and Thauera selenatis. New isolates and also sequences of so far uncultured bacteria from roots of Kallar grass were assigned to the genus Azoarcus as well. Also, strains degrading monoaromatic hydrocarbons anaerobically in the presence of nitrate clustered within this genus, albeit not with grass-associated isolates. All representative members of the five species harboring rhizospheric bacteria were able to form N2O from nitrate and showed anaerobic growth on malic acid with nitrate but not on toluene. In order to visualize different Azoarcus spp. by whole-cell in situ hybridizations, we generated 16S rRNA-targeted, fluorescent probes by in vitro transcription directly from PCR products which spanned the variable region V2. Hybridization was species specific for Azoarcus communis and Azoarcus indigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793947 TI - Correction of the beta-mannanase domain of the celC pseudogene from Caldocellulosiruptor saccharolyticus and activity of the gene product on kraft pulp. AB - The celA, manA, and celB genes from Caldocellulosiruptor saccharolyticus compose a cellulase-hemicellulase gene cluster and are arranged on a 12-kb C. saccharolyticus genomic fragment of the recombinant lambda bacteriophage NZP lambda 2. The beginning of a fourth open reading frame (celC) which was homologous to the C. saccharolyticus manA and celA genes was located at the 3' end of the 12-kb NZP lambda 2 genomic fragment. Genome-walking PCR was used to isolate DNA fragments downstream of the C. saccharolyticus celB gene, and the entire nucleotide sequence of celC was obtained. From the preliminary nucleotide sequence, celC appeared to encode yet another multidomain bifunctional enzyme (CelC) consisting of an N-terminal endo-1,4-beta-D-glucanase domain (75% similar to CelA domain 1), two central cellulose-binding domains, and a C-terminal endo 1,4-beta-D-mannanase domain (98% similar to ManA domain 1). However, upon completion of the celC sequencing, two -1 frameshifts were identified in the region encoding the putative CelC mannanase domain. The isolated CelC mannanase domain exhibited no beta-mannanase activity, which supported this observation. Recombinant PCR was used to correct the celC frameshifts by inserting the appropriate nucleotides into the gene. The repaired celC fragment containing the base insertions (manB) expressed strong beta-mannanase activity on soluble mannan substrates and showed significant activity on kraft pulp as judged by the release of reducing sugars. PMID- 7793948 TI - Unraveling the extent of diversity within the order Planctomycetales. AB - The phylogenetic positions of 22 isolates that morphologically resemble members of the family Planctomycetaceae were determined by sequence analysis of genes coding for 16S rRNA. While nine and eight isolates could be assigned to the genera Planctomyces and Pirellula, respectively, three strains grouped near Isosphaera pallida and one strain was closely related to Gemmata obscuriglobus. No isolate was found to be related to a previously described species of any of the four genera at the species level. Morphological characters and sequence idiosyncrasies of genes coding for 16S rRNA of the isolates generally correlated with features described for the four genera to which the isolates could be assigned. One strain stands phylogenetically isolated and may be representative of a novel genus of the family. Comparison with environmental clone sequences representing planctomycetes in soil and water revealed that three of the novel isolates were related to one clone of soil origin, but no close relationships between clones and the other new strains were found. The study reveals that the biodiversity of planctomycetes is significantly greater than was previously determined. PMID- 7793949 TI - Evidence for the existence of distinct populations of Vibrio anguillarum serogroup O1 based on plasmid contents and ribotypes. AB - A total of 103 Vibrio anguillarum serogroup O1 strains displaying 15 different plasmid profiles were characterized with respect to biochemical properties and ribotypes. The results confirmed that V. anguillarum O1 is a biochemically homogeneous group. The 103 strains could be allocated to three main clusters with high similarity coefficients. None of the biochemical properties were connected with the presence of plasmids. In total, 12 different ribotypes were demonstrated, with HindIII being used as the restriction enzyme. Forty of the strains were isolated from the same Danish fish farm, some from the kidneys of diseased fish and some from the environment, and some strains were isolated from the mucus, gills, and feces of healthy fish. Nineteen of these isolates possessed the 67-kb virulence plasmid alone or in combination with other plasmids, while 21 had no plasmids. All strains isolated from the kidneys of diseased fish on this farm had plasmids. Irrespective of their origin (kidneys, gills, or mucus), all 19 strains carrying the 67-kb virulence plasmid had the same ribotype, profile 1, while isolates without plasmids belonged to five different profiles, all different from profile 1. These results suggest that pathogenic V. anguillarum O1 strains possessing a virulence plasmid and nonpathogenic strains without plasmids from a small geographical area and even from the same fish may constitute two essentially distinct populations. Thus, it may be suggested that an exchange of virulence plasmids among strains is unlikely to occur in vivo. PMID- 7793950 TI - Massive fungal contamination in animal care facilities traced to bedding supply. AB - During the course of immunologic studies involving the gastrointestinal colonization of mice with Candida albicans, it became apparent that the animals were being exposed to large numbers of Aspergillus fumigatus spores which interfered with the C. albicans colonization. To determine the source of the A. fumigatus exposure and the extent of fungal contamination of the medical school vivarium and four satellite facilities, fungal analyses of feed, bedding, and air were undertaken. Initial samples from the air were collected with 3-h settle plates; air sampling following cleanup was done with an Anderson air sampler. The source of contamination in the mouse rooms was determined to be Beta Chip bedding, which came from the manufacturer highly contaminated. Beta Chip bedding (1 g) obtained from the manufacturer just prior to testing contained 10(4) CFU of A. fumigatus, 20 CFU of a zygomycete, and 10 CFU of a Penicillium sp. Coarse grade Beta Chip had approximately one-half those levels of contamination. Pure Cob bedding was highly contaminated also, but with a Fusarium sp. and a Cladosporium sp. Untreated and heat-treated Sani-Chip as well as all other heat treated preparations obtained from the manufacturer contained no detectable spores. Rodent chow direct from the manufacturer had no A. fumigatus, although it did contain 150 CFU of fungus per g, including 80 CFU of a Rhodotorula sp., 60 CFU of Cryptococcus uniguttulatus, and 1 CFU of a Penicillium sp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7793951 TI - Overexpression of the robA gene increases organic solvent tolerance and multiple antibiotic and heavy metal ion resistance in Escherichia coli. AB - Escherichia coli K-12 OST3410 was isolated previously as a stable cyclohexane tolerant mutant derived from cyclohexane-sensitive strain JA300. A plasmid which provides cyclohexane tolerance to strain JA300 was isolated from the OST3410 genomic library. Subcloning and sequence analysis showed that the plasmid contained the robA gene, whose gene product was reported to bind specifically to the right border of oriC. We observed that the robA gene on the multicopy plasmid generally increased the organic solvent tolerance of several E. coli strains. We also observed an increase in the organic solvent tolerance of JA300 carrying the lac-robA fusion gene on a low-copy plasmid by isopropyl-beta-D thiogalactopyranoside induction. Strain JA300 carrying the multicopy robA plasmid also showed an increase in resistance to a number of unrelated antibiotics and heavy metal ions, and the spectrum of resistance was significantly similar to that of the soxS-overexpressing strain. PMID- 7793952 TI - PCR analysis of the viral complex associated with La France disease of Agaricus bisporus. AB - Reverse transcription PCR analysis was used to investigate the involvement of two RNA-genome viruses, La France isometric virus (LIV) and mushroom bacilliform virus (MBV), in the etiology of La France disease of the cultivated mushroom Agaricus bisporus. Reverse transcription PCR amplification of sequences targeted to the genomes of LIV and MBV, with a sensitivity of detection of < 10 fg of viral RNA, showed diseased mushrooms to be either singly infected by LIV or doubly infected by LIV and MBV. Of 70 geographically diverse diseased mushroom isolates, 100% were infected by LIV, whereas almost 60% of these isolates were coinfected by MBV. Of 58 mushroom isolates determined to be free of infection by LIV, 3 were found to be infected by MBV. This represents the first documented report of the independent replication of these two viruses. Our data support the hypothesis that La France disease is associated with infection by two autonomously replicating viruses in which LIV is the primary causal agent and MBV, although possibly pathogenic and capable of modulating symptoms, is not required for pathogenesis. PMID- 7793953 TI - Effect of oxytetracycline-medicated feed on antibiotic resistance of gram negative bacteria in catfish ponds. AB - The effect of oxytetracycline-medicated feeds on antibiotic resistance in gram negative bacteria from fish intestines and water in catfish ponds was investigated. In experiments in the fall and spring, using ponds with no previous history of antibiotic usage, percentages of tetracycline-resistant bacteria in catfish intestines obtained from medicated ponds increased significantly after 10 days of treatment. In the fall, resistance of the intestinal and aquatic bacteria returned to pretreatment levels within 21 days after treatment. In the spring, resistance declined after treatment but remained higher than pretreatment levels for at least 21 days in intestinal bacteria and for 5 months in aquatic bacteria. Plesiomonas shigelloides, Aeromonas hydrophila, and Citrobacter freundii were isolated frequently in both spring and fall; Escherichia coli, Klebsiella pneumoniae, Edwardsiella tarda, and Enterobacter spp. were isolated primarily in the spring. Oxytetracycline treatment did not affect the distribution of bacterial species in the fall but may have accelerated a shift toward greater prevalence of members of the family Enterobacteriaceae in the spring. Multiple antibiotic resistance did not appear to be elicited by oxytetracycline treatment. PMID- 7793954 TI - A serine (threonine) protein kinase confers fungicide resistance in the phytopathogenic fungus Ustilago maydis. AB - A mutant of Ustilago maydis (VR43) with single-gene resistance to the dicarboximide fungicide vinclozolin was previously isolated and characterized. A genomic library was constructed, and an 8.7-kb resistance-conferring fragment was isolated by sib selection. Sequencing this fragment, we identified an 1,218-bp open reading frame, which, if disrupted by deletion, no longer confers resistance. Analyses of the data in GenBank demonstrated a high degree of homology between the product of the 1,218-bp open reading frame, referred to as the adr-1 gene, and Ser (Thr) protein kinases. PMID- 7793955 TI - Characterization of chemoautotrophic bacterial symbionts in a gutless marine worm Oligochaeta, Annelida) by phylogenetic 16S rRNA sequence analysis and in situ hybridization. AB - The phylogenetic relationships of chemoautotrophic endosymbionts in the gutless marine oligochaete Inanidrilus leukodermatus to chemoautotrophic ecto- and endosymbionts from other host phyla and to free-living bacteria were determined by comparative 16S rRNA sequence analysis. Fluorescent in situ hybridization confirmed that the 16S rRNA sequence obtained from these worms originated from the symbionts. The symbiont sequence is unique to I. leukodermatus. In phylogenetic trees inferred by both distance and parsimony methods, the oligochaete symbiont is peripherally associated with one of two clusters of chemoautotrophic symbionts that belong to the gamma subdivision of the Proteobacteria. The endosymbionts of this oligochaete form a monophyletic group with chemoautotrophic ectosymbionts of a marine nematode. The oligochaete and nematode symbionts are very closely related, although their hosts belong to separate, unrelated animal phyla. Thus, cospeciation between the nematode and oligochaete hosts and their symbionts could not have occurred. Instead, the similar geographic locations and habitats of the hosts may have influenced the establishment of these symbioses. PMID- 7793956 TI - PCR-mediated analysis of lignocellulolytic gene transcription by Phanerochaete chrysosporium: substrate-dependent differential expression within gene families. AB - We compare the kinetics of appearance of supernatant enzyme activities (lignin peroxidase, manganese peroxidase, and cellulase) and gene expression (LIG, mnp, and cbhI gene families and the unique cbhII gene) in Phanerochaete chrysosporium ME446 when grown on four different carbon sources: ball-milled straw, representing the natural substrate lignocellulose; Avicel as a crystalline cellulose; and high and low concentrations of glucose, in all cases with limiting nitrogen. PCR-based technology utilizing pairs of primers specific for particular genes showed that there is differential expression between and within the families. There were a number of instances of mRNA species being present only on a single day, implying tight regulation of lignocellulose degradation at the mRNA level. The patterns of extracellular enzyme activities and mnp and cbh gene expression are similar whereas LIG gene expression can be detected when no corresponding enzyme activity is observed in the extracellular supernatant. The enzyme produced under these conditions is presumably sequestered by the mycelium and is likely to be functionally significant. Another striking result is that cellulose, in the form of Avicel, elicits the expression of three LIG gene for which there is no expression under the same conditions with the other carbon sources. PMID- 7793959 TI - Differentiation of Aspergillus parasiticus from Aspergillus sojae by random amplification of polymorphic DNA. AB - Aspergillus parasiticus and Aspergillus sojae are two morphologically similar species belonging to the Aspergillus section flavi. A new method to distinguish the two species, the aflatoxin producer A. parasiticus and the koji mold A. sojae, was developed. Single primers with arbitrary sequences were used to generate random amplified polymorphic DNA (RAPD) markers from strains of these two species. Three decamers, OPA-04, OPB-10, and OPR-01, allowed adequate discrimination between strains of A. parasiticus and A. sojae in RAPD analyses. A. sojae was further separated into group I and group II with the three primers. On the other hand, A. parasiticus was divided into group A and group B when amplified with OPA-04 and OPR-10 primers. The previously misidentified stain CCRC 32423 and the misclassified strain CCRC 30227 were identified as Aspergillus flavus and A. sojae, respectively, on the basis of RAPD patterns and morphological characteristics. We suggest that the RAPD technique is a rapid and reliable tool to distinguish A. parasiticus from A. sojae. PMID- 7793957 TI - Comparative mapping of aflatoxin pathway gene clusters in Aspergillus parasiticus and Aspergillus flavus. AB - Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and A. parasiticus. Aflatoxins are synthesized by condensation of acetate units; their synthesis is estimated to involve at least 16 different enzymes. In this study we have shown that at least nine genes involved in the aflatoxin biosynthetic pathway are located within a 60-kb DNA fragment. Four of these genes, nor-1, aflR, ver-1, and omtA (previously named omt-1), have been cloned in A. flavus and A. parasiticus. In addition, five other genes, pksA, uvm8, aad, ord-1, and ord-2 have been recently cloned in A. parasiticus. The pksA, aad, and uvm8 genes exhibit sequence homologies to polyketide synthase, aryl-alcohol dehydrogenase, and fatty acid synthase genes, respectively. The cDNA sequences of ord-1 and ord-2 genes, which may be involved in later steps of aflatoxin biosynthesis, have been determined; the ord-1 gene product exhibits homology to cytochrome P-450-type enzymes. By characterizing the overlapping regions of the DNA inserts in different cosmid and lambda DNA clones, we have determined the order of these aflatoxin pathway genes within this 60-kb DNA region to be pksA, nor-1, uvm8, aflR, aad, ver-1, ord-1, ord-2, and omtA in A. parasiticus and nor-1, aflR, ver-1, ord-1, ord-2, and omtA in A. flavus. The order is related to the order in enzymatic steps required for aflatoxin biosynthesis. The physical distances (in kilobase pairs) and the directions of transcription of these genes have been determined for both aflatoxigenic species. PMID- 7793958 TI - Increased expression of Aspergillus parasiticus aflR, encoding a sequence specific DNA-binding protein, relieves nitrate inhibition of aflatoxin biosynthesis. AB - The aflR gene from Aspergillus parasiticus and Aspergillus flavus may be involved in the regulation of aflatoxin biosynthesis. The aflR gene product, AFLR, possesses a GAL4-type binuclear zinc finger DNA-binding domain. A transformant, SU1-N3 (pHSP), containing an additional copy of aflR, showed increased transcription of aflR and the aflatoxin pathway structural genes, nor-1, ver-1, and omt-1, when cells were grown in nitrate medium, which normally suppresses aflatoxin production. Electrophoretic mobility shift assays showed that the recombinant protein containing the DNA-binding domain, AFLR1, bound specifically to the palindromic sequence, TTAGGCCTAA, 120 bp upstream of the AFLR translation start site. Expression of aflR thus appears to be autoregulated. Increased expression of aflatoxin biosynthetic genes in the transformant might result from an elevated basal level of AFLR, allowing it to overcome nitrate inhibition and to bind to the aflR promotor region, thereby initiating aflatoxin biosynthesis. Results further suggest that aflR is involved in the regulation of multiple parts of the aflatoxin biosynthetic pathway. PMID- 7793960 TI - Distribution of cryV-type insecticidal protein genes in Bacillus thuringiensis and cloning of cryV-type genes from Bacillus thuringiensis subsp. kurstaki and Bacillus thuringiensis subsp. entomocidus. AB - DNA dot blot hybridizations with a cryV-specific probe and a cryI-specific probe were performed to screen 24 Bacillus thuringiensis strains for their cryV-type (lepidopteran- and coleopteran-specific) and cryI-type (lepidopteran-specific) insecticidal crystal protein gene contents, respectively. The cryV-specific probe hybridized to 12 of the B. thuringiensis strains examined. Most of the cryV positive strains also hybridized to the cryI-specific probe, indicating that the cryV genes are closely related to cryI genes. Two cryV-type genes, cryV1 and cryV465, were cloned from B. thuringiensis subsp. kurstaki HD-1 and B. thuringiensis subsp. entomocidus BP465, respectively, and their nucleotide sequences were determined. The CryV1 protein was toxic to Plutella xylostella and Bombyx mori, whereas the CryV465 protein was toxic only to Plutella xylostella. PMID- 7793961 TI - Cloning and sequencing of a laccase gene from the lignin-degrading basidiomycete Pleurotus ostreatus. AB - The gene (pox1) encoding a phenol oxidase from Pleurotus ostreatus, a lignin degrading basidiomycete, was cloned and sequenced, and the corresponding pox1 cDNA was also synthesized and sequenced. The isolated gene consists of 2,592 bp, with the coding sequence being interrupted by 19 introns and flanked by an upstream region in which putative CAAT and TATA consensus sequences could be identified at positions -174 and -84, respectively. The isolation of a second cDNA (pox2 cDNA), showing 84% similarity, and of the corresponding truncated genomic clones demonstrated the existence of a multigene family coding for isoforms of laccase in P. ostreatus. PCR amplifications of specific regions on the DNA of isolated monokaryons proved that the two genes are not allelic forms. The POX1 amino acid sequence deduced was compared with those of other known laccases from different fungi. PMID- 7793962 TI - Overproduction, purification, and biochemical characterization of a xylanase (Xys1) from Streptomyces halstedii JM8. AB - Streptomyces halstedii JM8, isolated from straw, produces and secretes into the culture supernatant at least two proteins with hydrolytic activity towards xylan. The cloning of a DNA fragment of this microorganism in several Streptomyces strains permitted us to overproduce both proteins. N-terminal sequence analyses, immunoblot assays, and time course overproduction experiments allowed us to ensure that both xylanases were encoded by the same gene and that the smallest form (35 kDa) originated from the large one (45 kDa) by proteolytic cleavage on the C terminus. The production of both forms was studied in different strains carrying the gene in a multicopy plasmid. The best production was obtained with Streptomyces parvulus transformed with the plasmid pJM9, a pIJ702 derivative, which yielded 144 U/ml. Both forms of the xylanase were purified with a fast performance liquid chromatography system and characterized biochemically. The optimal pH and temperature, for both, were 6.3 and 60 degrees C, respectively, in 7.5-min assays. Both proteins were highly stable in a wide range of pHs (4 to 10) and temperatures (4 to 50 degrees C); nevertheless, after 1-h incubations, both enzymes lost most of their activity at temperatures over 55 to 60 degrees C. Endoxylanolytic activity was demonstrated in both enzymes, but no beta-xylosidase activity was detected. PMID- 7793963 TI - Cloning and DNA sequencing of xyaA, a gene encoding an endo-beta-1,4-xylanase from an alkalophilic Bacillus strain (N137). AB - The gene xyaA encoding an alkaline endo-beta 1,4-xylanase from an alkalophilic Bacillus sp. strain (N137) isolated in our laboratory was cloned and expressed in Escherichia coli. The nucleotide sequence of a 1,656-bp DNA fragment containing xyaA was determined, revealing one open reading frame of 993 bp that encodes a xylanase (XyaA) of 39 kDa. This xylanase lacks a typical putative signal peptide, yet the protein is found in the Bacillus culture supernatant. In Escherichia coli, the active protein is located mainly in the periplasmic space. The xylanase activity of the cloned XyaA is an endo-acting enzyme that shows optimal activity at pH 8 and 40 degrees C. This activity is stable at a pH between 6 and 11. Incubations of XyaA at 40 degrees C for 1 h destroyed 45% of the activity. PMID- 7793964 TI - Enhanced fermentation of mannitol and release of cytotoxin by Clostridium difficile in alkaline culture media. AB - Clostridium difficile ATCC 43255 fermented less than 10% of the mannitol in a medium at pH 7; however, when the initial pH of the medium was adjusted to 8.5 or 9, about 80% of the mannitol was fermented. Cell extracts of C. difficile phosphorylated mannitol with phosphoenolpyruvate, not ATP, indicating a phosphoenolpyruvate phosphotransferase system transport phosphorylation of mannitol. The phosphorylation product was dehydrogenated by D-mannitol-1 phosphate:NAD oxidoreductase. Growth at an initial pH of 8.5 yielded cytotoxin titers of 10(7) to 10(8) in Trypticase-yeast extract-mannitol medium, wit a titer of 10(8) as early as 13 h. PMID- 7793965 TI - The Lly protein protects Legionella pneumophila from light but does not directly influence its intracellular survival in Hartmannella vermiformis. AB - The lly locus (legiolysin) mediates the browning of the culture medium of Legionella pneumophila in the late stationary growth phase, presumably as a result of synthesis of homogentisic acid. Mutagenesis of the lly gene of the L. pneumophila Philadelphia I derivative JR32 did not affect intracellular replication in the natural host Hartmannella vermiformis. The Lly-negative mutant, however, showed a markedly decreased resistance to ordinary light. The cloned lly gene conferred an increased resistance to light in recombinant L. pneumophila and Escherichia coli K-12, indicating a contribution of the Lly protein to ecological adaptation of Legionella species. PMID- 7793966 TI - Rapid large-scale growth of Helicobacter pylori in flasks and fermentors. AB - We developed procedures for large-scale cultivation of Helicobacter pylori in flasks and fermentors. Flasks incubated closed under a microaerophilic gas phase with a cotton plug covered by a plastic bag, followed by removal of the bag after 8 h, gave excellent growth. Growth in a 10-liter fermentor led to excessive foaming if the medium was sparged with gas; silicone- or polyglycol-based antifoaming agents were severely inhibitory. Use of fermentor surface gassing, first with a microaerophilic 6% oxygen gas mixture, then with air, and then with 95% oxygen, allowed the culture to grow to an A600 of 2.5 in < 24 h. This method was modified for scale-up to a 100-liter fermentor. PMID- 7793967 TI - Complexation of nicotinamide adenine dinucleotide with ferric and ferrous ions. AB - Motivated by the observed influence of stainless steel and ferric and ferrous ions on the behavior of the peroxidase/oxidase oscillator, the mechanism and kinetics of interaction of 1,4-dihydronicotinamide adenine dinucleotide (NADH) with iron ions in 0.1 M acetic acid/sodium acetate buffer with pH 5.1 and with the solution/stainless steel interface were extensively studied. The character of a possible mutual influence of NADH/acetate buffer solution and Type 316 stainless steel has been investigated. We also suggest the mechanism of stainless steel corrosion inhibition by NADH. It was determined that fast complexation of ferric and ferrous ions with NADH occurred with rate constant kcompl = 4.0 x 10(9) +/- 0.2 x 10(9) M-1 s-1. The composition of the product complex is [Fe (NADH)2] for both Fe2+ and Fe3+. A previously unreported complex of ferrous ion and NADH was discovered, determined, and separately investigated. Kinetic and equilibrium constants for reactions of iron ions-NADH complexation and following redox processes of the complex decomposition were determined from spectrophotometric and electrochemical experiments. PMID- 7793968 TI - Protein oxidation and aging. I. Difficulties in measuring reactive protein carbonyls in tissues using 2,4-dinitrophenylhydrazine. AB - A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This hypothesis is based on a series of reports showing an age-dependent increase in protein carbonyl content and an age dependent loss of enzyme function. This hypothesis is also supported by the report of a novel effect of N-tert-butyl-alpha-phenylnitrone (PBN) in reversing these age-dependent changes. Here we specifically study the method that was used to measure reactive protein carbonyls in tissues. This method uses 2,4 dinitrophenylhydrazine (DNPH) and includes a washing procedure. Our results indicate that reactive protein carbonyls in normal crude tissue extracts cannot be reliably measured by this method, although it does reliably measure reactive carbonyls in purified proteins which have been oxidatively modified in vitro. The nucleic acids in tissues could be a major problem encountered in the assay. Using the streptomycin sulfate treatment combined with a dialysis step, we were successful in removing most nucleic acids from a crude tissue extract, but then the reactive carbonyl level in the crude tissue extract was too low to be reliably measured. This streptomycin sulfate treatment procedure, however, had no effect on the reactive carbonyl measurement of an oxidized protein sample. The unwashed free DNPH was another major problem in the assay because of its very strong absorption around 370 nm, where reactive carbonyls were quantitated. Nevertheless, on using the procedure described in the literature to measure total "reactive carbonyls" in rat liver and gerbil brain cortex, no change with age or PBN treatment was found. Then, we investigated a HPLC procedure which uses sodium dodecyl sulfate in the mobile phase but this was also found to be unsuitable for the reactive protein carbonyl assay in tissues. PMID- 7793970 TI - Cloning, sequencing, and expression of the dipeptidyl peptidase IV gene from Flavobacterium meningosepticum in Escherichia coli. AB - The dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) gene from Flavobacterium meningosepticum was cloned by Southern and colony hybridizations using probes amplified by PCR, and expressed in Escherichia coli DH1. E. coli DH1 harboring pFDP-H1, which was a subclone derived from the positive clone pFDP-1, showed 3.5 fold higher activity than F. meningosepticum. Nucleotide sequencing analysis revealed an open reading frame of 2133 bp, coding for a protein of 711 amino acids with a predicted molecular weight of 80,626. The expressed enzyme in E. coli DH1/pFDP-H1 was purified about 345-fold with an activity recovery of 12.3%. The molecular weight of the purified enzyme was estimated to be 75,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 160,000 by gel filtration, respectively, suggesting a dimeric form of the native enzyme. The deduced amino acid sequence of DP IV was homologous to those of the serine proteases of the "prolyl endopeptidase family." A sequence near the C-terminal region and the putative catalytic triad residues were well conserved among these enzymes. PMID- 7793969 TI - Acid-base chemical mechanism of aspartase from Hafnia alvei. AB - An acid-base chemical mechanism is proposed for Hafnia alvei aspartase in which a proton is abstracted from C-3 of the monoanionic form of L-aspartate by an enzyme general base with a pK of 6.3-6.6 in the absence and presence of Mg2+. The resulting carbanion is presumably stabilized by delocalization of electrons into the beta-carboxyl with the assistance of a protonated enzyme group in the vicinity of the beta-carboxyl. Ammonia is then expelled with the assistance of a general acid group that traps an initially expelled NH3 as the final NH4+ product. In agreement with the function of the general acid group, potassium, an analog of NH4+, binds optimally when the group is unprotonated. The pK for the general acid is about 7 in the absence of Mg2+, but is increased by about a pH unit in the presence of Mg2+. Since the same pK values are observed in the pKi(succinate) and V/K pH profile, both enzyme groups must be in their optimum protonation state for efficient binding of reactant in the presence of Mg2+. At the end of a catalytic cycle, both the general base and general acid groups are in a protonation state opposite that in which they started when aspartate was bound. The presence of Mg2+ causes a pH-dependent activation of aspartase exhibited as a partial change in the V and V/Kasp pH profiles. When the aspartase reaction is run in D2O to greater than 50% completion no deuterium is found in the remaining aspartate, indicating that the site is inaccessible to solvent during the catalytic cycle. PMID- 7793971 TI - Inactivation of an animal and a fungal catalase by hydrogen peroxide. AB - We have quantitatively compared the rates of peroxide-dependent inactivation of bovine liver catalase and Aspergillus niger catalase as class representatives of catalases that contain tightly bound NADPH and those that do not. Inactivation of these catalases in the presence of ethanol has also been quantitated in an effort to assess the importance of compound II, an inactive form of bovine liver catalase, in the inactivation reaction. The values of k2, the second-order rate constant for inactivation calculated for the bovine enzyme, in the absence and presence of ethanol, respectively, were 8.9 +/- 0.26 and 8.5 +/- 0.27 M-1 min-1. In contrast, the values for the A. niger enzyme were 0.51 +/- 0.069 and 10.5 +/- 0.32 M-1 min-1. The A. niger enzyme is more stable toward hydrogen peroxide induced inactivation than the liver enzyme. The A. niger enzyme is markedly destabilized by 20 mM ethanol, whereas the inactivation of the liver enzyme is unaffected by ethanol. Reaction of bovine liver catalase with ethyl hydroperoxide produced the characteristic absorption spectrum of compound I and in the absence of ethanol the spectrum associated with compound II. In contrast, the fungal enzyme developed compound I spectrum but spectral changes that might be ascribed to compound II were barely detected in the Soret region. Spectral changes for A. niger catalase in the visible region were modified by the presence of ethanol but could not be clearly correlated with the bovine catalase compound II spectra either in the presence or absence of ethanol. The stability of the fungal and bovine catalases in the presence of hydrogen peroxide is quantitatively documented. The enzymes are also shown to be different in their response to ethanol and in the formation of compound II-like species with ethyl hydroperoxide. It appears unlikely that compound II is an intermediate in the hydrogen peroxide-mediated inactivation reaction of either catalase under catalatic assay conditions. PMID- 7793972 TI - Inhibition of alpha-chymotrypsin with an enzyme-activated n-nitrosoamide: active site labeling by the naphthylmethyl cation. AB - alpha-Chymotrypsin was irreversibly inhibited with an enzyme-activated N nitrosamide inhibitor, N-nitroso-N-(1-naphthylmethyl)-N'-isobutyrylalanine; alkylation of the active-site residues by the naphthylmethyl cation produced in the enzymatic reaction occurred. The inhibited enzyme was reduced and aminoethylated and then subjected to tryptic and chymotryptic digestion. Separation of the digest by reversed-phase HPLC revealed one major new peak relative to that of a control run from the native enzyme. Subsequent amino acid analysis and sequencing along with fast atom bombardment-mass spectrometry measurements indicated that this new peak stemmed from an active-site peptide, Met-192-Leu-199, and that the naphthylmethyl label was attached to the side-chain oxygen of Ser-195. The general approach employed can be applied to labeling active sites of a variety of hydrolytic enzymes. PMID- 7793975 TI - Magnetic resonance of Fe-S clusters: isolation and characterization of a 7Fe ferredoxin from Rhodopseudomonas palustris. AB - A novel iron-sulfur protein from the photosynthetic purple bacterium Rhodopseudomonas palustris was purified to homogeneity and identified as a ferredoxin on the basis of its physicochemical properties. Based on the uv/vis spectrum, iron quantitation, cyclic voltammetry, EPR, and 1H NMR data, the ferredoxin is found to contain two iron-sulfur clusters, one [3Fe-4S] and one [4Fe-4S], which places this protein in the class of 7Fe ferredoxins. The voltammetric peak potentials of the two clusters are -0.260 and -0.560 V at pH 8.0. The molecular mass around 19 kDa makes this protein the heaviest known in this class. This paper further demonstrates the diagnostic power of magnetic resonance spectroscopies in recognition of the two types of clusters in iron sulfur proteins. PMID- 7793973 TI - Reexamination of properties of prophenoloxidase isolated from larval hemolymph of the silkworm Bombyx mori. AB - Prophenoloxidase in hemolymph of the silkworm (Bombyx mori) was purified by the method of Ashida (Ashida, M. (1971) Arch. Biochem. Biophys. 144, 749-762) with slight modifications to further increase the purity, and its properties were reinvestigated. The purified prophenoloxidase gave two discrete bands in isoelectric focusing-polyacrylamide gel electrophoresis (IEF-PAGE) (pI 4.95 and 4.98) and in native-polyacrylamide gel electrophoresis with 4.5% separating gel. Each band in IEF-PAGE was separated into two bands in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with mobilities corresponding to 71.5- and 71-kDa polypeptides. In HPLC on octadecyl column the prophenoloxidase preparation gave two well-separated symmetrical peaks (proPO polypeptide I and proPO polypeptide II). The molecular masses of the proPO polypeptides I and II were determined to be 71.5 and 71 kDa in SDS-PAGE and 78,880 and 81,105 Da by matrix-assisted laser desorption ionization mass spectrometry, respectively. Native prophenoloxidase was eluted at a position corresponding to 126-kDa protein in gel permeation chromatography. Amino acid compositions and peptide mappings of proPO polypeptides indicated that both polypeptides differ in their primary structures. These results are discussed in relation to the subunit structure, the presence of bicopper cluster, and the polymorphism of prophenoloxidase in silkworm hemolymph. PMID- 7793974 TI - Molecular cloning and sequence analysis of cDNAs for metalloproteinases from broad-banded copperhead Agkistrodon contortrix laticinctus. AB - The cDNA sequences of two related genes coding for metalloproteinases from a venom gland library of Agkistrodon contortrix laticinctus have been determined. The ACLPREH cDNA codes for a 220-amino acid zinc-dependent hemorrhagic metalloproteinase, and the predicted sequence is in agreement with the N-terminal sequence of the previously purified protein. ACLPREF cDNA sequence predicts a 222 amino acid molecule having strong similarity to fibrolase, a fibrinolytic enzyme isolated from A. contortrix contortrix venom that is reported to be devoid of hemorrhagic activity. Both cDNAs present the same pattern of domain organization as other members of the metalloproteinase/disintegrin gene family. They code for short toxins which do not have the disintegrin domain and have three-disulfide bonds in the metalloproteinase domain. Both cDNA sequences have the highly conserved 5' and 3' untranslated regions that have been described for the metalloproteinase and phospholiphase A2 snake venom gene families. ACLPREH and ACLPREF cDNAs share a higher degree of homology in the untranslated regions and proenzyme domain than in the mature protein domain. The amino acid sequences of hemorrhagic and/or fibrinolytic metalloproteinases demonstrate that a few substitutions may result in different enzymatic activities. Also, some of these toxins have valine instead of isoleucine in the CIM Met-turn consensus sequence. From our data, we can suggest that snake venom fibrinolytic metalloproteinase genes belong to the metalloproteinase/disintegrin gene family. This is the first report of cDNA sequences of small snake venom metalloproteinases having three disulfide bonds in the metalloproteinase domain. PMID- 7793976 TI - Spin-labeling study of the oxidative damage to low-density lipoprotein. AB - In this study, we have spin-labeled the lysine and cysteine residues of low density lipoprotein (LDL) using N-4-(2,2,6,6-tetramethylpiperidinyl-1-oxyl-4-yl) maleimide (MAL-6) and succinimidyl-2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3 carboxylate (SSL), respectively. The electron spin resonance (ESR) spectrum of SSL bound to LDL indicated that the nitroxide moiety was relatively mobile. In contrast, the ESR spectrum of MAL-6 bound to LDL showed that the nitroxide moiety was rotationally restricted. Using the continuous-wave power saturation technique in the presence of hydrophobic and hydrophilic paramagnetic relaxing agents, we have determined that (i) approximately 60-70% of lysine-bound SSL is exposed to the aqueous phase, (ii) approximately 30-40% of SSL-LDL is buried in a hydrophobic region, and (iii) MAL-6 bound to LDL is localized predominantly in the hydrophobic region. During Cu(2+)-initiated oxidation of spin-labeled LDL, nitroxide labels located in a hydrophobic environment were predominantly degraded. Nitroxide destruction was inhibited by butylated hydroxytoluene, indicating the role of lipid peroxidation in this process. ESR data also showed that Cu2+ binding to lysine is essential for LDL oxidation. The spin label methodology may be useful for the investigation of site-specific radical reactions in LDL. PMID- 7793977 TI - Functional assessment of specific amino acid residues of cytochrome P4501A1 using anti-peptide antibodies. AB - Several positively charged amino acid residues in cytochrome P450 have been shown to be involved in the electrostatic association with NADPH-cytochrome P450 reductase. For cytochrome P4501A1, five regions were proposed as the putative binding sites for the reductase (Shen, S., and Strobel, H. W. (1993) Arch. Biochem. Biophys. 304, 257-265). To elucidate the specific roles of each of these amino acid residues, five anti-peptide antibodies defined as 1A, 4A, 5A, 6A, and 7A were generated against these regions containing 8-13 amino acids and were affinity-purified using a peptide-Sepharose 4B column. Analysis by enzyme-linked immunosorbent assay and protein immunoblot techniques demonstrated that three of five anti-peptide antibodies have specific binding to the peptides as well as to cytochrome P4501A1. Incubation of the various anti-peptide antibodies with cytochrome P450 followed by reconstitution with reductase, lipid, and NADPH resulted in significant inhibition of P450 activity for antibodies 5A and 6A, but not for 1A, 4A, or 7A. Antibody 5A also exhibited inhibition of P450 activity supported by cumene hydroperoxide, though the inhibition was 45 to 30% less than the inhibition of reductase-supported activity at each of the increasing concentrations of antibody. Kinetic studies with antibody 5A revealed no change in the Km for the substrate ethoxycoumarin, but rather a dramatic effect on the Vmax of the cytochrome P4501A1 system whether reconstituted with reductase or supported by cumene hydroperoxide. Characterization of the effects of antibody 5A on cytochrome P4501A1 suggested that the binding of antibody 5A to P4501A1 may change the binding of P4501A1 with reductase. Furthermore, the binding of 5A to cytochrome P4501A1 also lowered the Vmax of the P450. These results are consistent with the roles for the regions of cytochrome P4501A1 from amino acid residues 269 to 281 (peptide 5) and 454 to 463 (peptide 6) in cytochrome P4501A1 hydroxylation activity. PMID- 7793978 TI - The influence of antibiotics and antitumor agents on the relaxation activity of Pisum sativum leaf chloroplast topoisomerase I. AB - DNA topoisomerase was isolated from pea leaf chloroplasts. The relaxation activity of this topoisomerase was Mg2+ dependent and sensitive to ethidium bromide and novobiocin, a gyrase inhibitor. Chloroplast topoisomerase (Topo I) was ATP independent, as shown by the characteristic gel distribution of topoisomers. Topoisomerase, compared with the known eucaryotic topoisomerase I, was not stimulated by polyamines as are spermidine, spermine, and cadaverine. Ethidium bromide, DAPI, heparin, nalidixic acid, and m-AMSA (but not camptothecin) were able to inhibit the relaxation activity of chloroplast topo I. Nalidixic acid, novobiocin, m-AMSA, camptothecin, and amiloride were tested for their effects on the topoisomerase-catalyzed "cleavage complex" between DNA and chloroplast DNA topoisomerase I. PMID- 7793979 TI - Phycobilin biosynthesis: reductant requirements and product identification for heme oxygenase from Cyanidium caldarium. AB - Algal heme oxygenase is a soluble enzyme from Cyanidium caldarium that catalyzes the first committed step of phycobilin biosynthesis by converting protoheme to biliverdin IX alpha. Although the physiological substrate (protoheme) of algal heme oxygenase is identical to that of microsomal heme oxygenase, which catalyzes heme catabolism in animals, the two enzyme systems differ in several respects including the nature of the required reductants and solubility of the enzymes. Addition of the strong Fe3+ ion chelators, desferrioxamine and Tiron (4,5 dihydroxy-1,3-benzenedisulfonic acid), greatly increased the yield of solvent extracted bilin product. The effect of the Fe3+ chelators was approximately equal whether they were added during or after the enzyme incubation. Postincubation treatment of the enzyme reaction mixture with strong acid also greatly increased the product yield. Addition of desferrioxamine to the reaction mixture after the incubation was terminated caused the appearance of an absorption spectrum, indicating an increase in the concentration of free bilin product. Acid and Fe3+ chelators are known to cause dissociation of Fe(III)-bilin complexes. These results indicate that the in vitro enzymic reaction product of algal heme oxygenase is a nonenzyme-bound Fe(III)-biliverdin IX alpha complex that is poorly extracted and/or quantitated unless it is first dissociated. Algal heme oxygenase required the simultaneous presence of both reduced ferredoxin and a second reductant such as ascorbate for activity. The requirement for L-ascorbate could be substituted by Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) or D-ascorbate, but not by dehydroascorbate or dithiothreitol. Heme oxygenase was purified over 200-fold from C. caldarium by differential (NH4)2SO4 precipitation and serial column chromatography over reactive blue 2-Sepharose, DEAE-cellulose, Sephadex G-75, and ferredoxin-Sepharose. PMID- 7793981 TI - Purification of human hepatic arginase and its manganese (II)-dependent and pH dependent interconversion between active and inactive forms: a possible pH sensing function of the enzyme on the ornithine cycle. AB - Purification of human liver arginase by chromatography on DEAE-Sepharose, CM Sepharose, hydroxylapatite, and MonoS yielded protein of greater than 95% purity by sodium dodecyl sulfate-gel electrophoresis. Detailed kinetic studies of the interconversion of active and inactive forms of arginase showed the effects of metal ion addition and withdrawal, metal ion type, time, temperature, and pH. At pH 7 and 37 degrees C, removal of Mn2+ caused a first-order deactivation with half-life of 1 h. Reactivation was completed within 0.5 min (1 mM Mn2+) or 90 min (ca. 6 nM Mn2+). Activation by Mn2+ showed a hyperbolic response, with Kd for Mn2+ of about 36 nM. Mn2+ apparently displaced about 2 H+, resulting in sigmoid dependence upon concentration of OH-. Both the maximal velocity of catalysis and the Km toward arginine were markedly pH-dependent in the physiological range. The findings lead to a model where Mn2+ allosterically activates arginase by a sequential, and pH-sensitive, mechanism. The combined pH sensitivities of activation, Vmax, and Km are likely to give arginase a role in mediating the demonstrated pH control of the ornithine cycle and hence in the regulation of body pH. PMID- 7793980 TI - Protein oxidation and aging. II. Difficulties in measuring alkaline protease activity in tissues using the fluorescamine procedure. AB - A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This is primarily based on a series of reports showing an age-dependent increase in protein carbonyl content and an age dependent decrease in the activities of enzymes, especially of alkaline proteases, which preferentially degrade oxidatively modified protein. Recently, this hypothesis was strongly supported by the report of a novel effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) in reversing these age-dependent changes. However, we found that the reactive protein carbonyls could not be reliably measured in tissues by using the 2,4-dinitrophenylhydrazine procedure described in the PBN study. We now focus on the alkaline protease activity assay and show that alkaline protease activity cannot be reliably measured in crude tissue extracts by using the fluorescamine procedure also described in the PBN study. We were, however, able to reliably measure a protease activity in crude tissue extracts at alkaline pH by using a synthetic fluorogenic peptide substrate, but no effect of aging or PBN treatment was found on the protease activity in rat brain cortexes. Thus, the reported age-dependent changes in protein carbonyl formation and alkaline protease activity remain to be confirmed. PMID- 7793983 TI - Stimulation of glycolysis by histidine buffers in mammalian liver during cold hypoxia. AB - This study was designed to address the reasons why glycolysis in mammalian liver is unable to function more efficiently during periods of cold hypoxia. Our hypothesis was that control of intracellular pH, by use of amino acid buffers with high pKa values, would allow prolonged flux through glycolysis and better maintenance of liver high-energy adenine nucleotide pool. The effects of two concentrations of histidine (90 and 180 mM) and one of carnosine (90 mM), a histidyl dipeptide, on energy metabolism and levels of glycolytic substrate (glucose) and anaerobic endproduct (lactate) were investigated during cold hypoxia using rat livers to model the mammalian system. The transition to anaerobic metabolism was apparent by an immediate rise in lactate levels upon entry into cold hypoxia. By 10-14 h hypoxia, contents of the endproduct had increased by 10, 13.5, and 14.5 mumol/g in buffers containing 90 and 180 mM histidine and 90 mM carnosine, respectively. As well, ATP, total adenylate contents, and "energy charge" ratios exhibited a rapid decline from initial values of 2.3-3.3 mumol/g, 4.3-5.5 mumol/g, and 0.64-0.75, respectively, over the first 2-4 h of cold hypoxia. With respect to efficacy, the 180 mM histidine buffer exhibited the most positive maintenance of adenylate levels, followed closely by 90 mM carnosine, and finally 90 mM histidine as the least effective of the three buffers. Nevertheless, all three buffers examined in this study showed positive effects compared to similarly treated livers stored in a solution of minor buffering capacity (a citrate-based solution) over the same time period. The data support the hypothesis that glycolytic flux and cellular energetics can be maintained by the inclusion of efficient buffering agents during periods of cold hypoxia. PMID- 7793982 TI - Cooperative manganese (II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: a biological pH-sensing mechanism in bacterial spore formation and germination. AB - The conversion of 3-P-glycerate mutase of Bacillus megaterium from a catalytically inactive to an active form was markedly more effective with buffered Mn2+ than with just added Mn2+. The previously reported stimulation by threonine disappeared when buffered Mn2+ was used. Activation of mutase showed a sigmoid dependence on Mn2+ concentration when buffered with tetramethylenediamine tetraacetate. The curve obeyed Hill kinetics with a coefficient of 2.1 +/- 0.1. At 0.5 microM free Mn2+, buffered with trimethylenediamine tetraacetate, activation of mutase increased about 73-fold over the pH range 6.6 to 7.4. Plotted against [OH-], the activation showed a strongly sigmoid response with Hill coefficient of 3.5 +/- 0.1. When mutase activated at pH 6.4 and 0.5 microM free Mn2+ in the presence of substrate was transferred to a similar medium at pH 7.4, the rate of product accumulation increased 360-fold within a few minutes. The pH sensitivity conferred upon mutase by low [Mn2+] may account for its large activity decrease during sporulation, and later increase during spore germination, when spore pH, respectively, declines and rises by about 1 unit. These changes result in the accumulation, and later reutilization, of 3-P glycerate reserves in the spore. Such a pH-sensing function of Mn2+ may have wider biological uses. PMID- 7793985 TI - Redox-dependent changes in beta-sheet and loop structures of Cu,Zn superoxide dismutase in solution observed by infrared spectroscopy. AB - Redox-dependent conformational changes of bovine Cu,Zn superoxide dismutase in 20 mM phosphate buffer (pH 7.4) were studied at 20 degrees C using Fourier transform infrared spectroscopy. Amide I spectra provide evidence that conformational changes in the protein accompany a change in the oxidation state of copper at the active site. Quantitative analysis of these spectra indicates that both reduced (CuI,ZnII) and oxidized (CuII,ZnII) enzymes are composed of about 35% antiparallel beta-sheet, 45% unordered/loop, and 20% beta-turn structures. Significant redox-dependent changes occur in regions ascribed to beta-sheet and unordered/loop structures that are consistent with an active channel structure wherein the copper ion bonds to imidazolate side chains of His 44, 46, and 118 within the beta-sheet structure and also to the imidazolate side chain of His 61 associated with unordered/loop structure. This study provides the first experimental evidence that an unordered structure can exhibit bands in more than one region, one near 1658 cm-1 and another near 1648 cm-1 in both H2O and D2O solutions. The detected changes in protein conformation are expected to be critical to the catalytic function of this enzyme. PMID- 7793984 TI - Reactive oxygen species and DNA damage in 2-bromo-(glutathion-S-yl) hydroquinone mediated cytotoxicity. AB - Exposure of renal proximal tubular epithelial cells (LLC-PK1) to the nephrotoxicants 2-bromo-6-(glutathion-S-yl)hydroquinone, 2-bromo-3-(glutathion-S yl)-hydroquinone, and 2-bromo-(diglutathion-S-yl)hydroquinone caused DNA fragmentation and cytotoxicity. Viability measured by lysosomal neutral red accumulation was the most sensitive parameter of cytotoxicity, and preceded toxicity determined by either the mitochondrial MTT assay or by measuring intracellular lactate dehydrogenase activity. DNA fragmentation was detected as early as 15 min after exposure to 2-bromo-6-(glutathion-S-yl)hydroquinone (100 microM), 2-bromo-3-(glutathion-S-yl)hydroquinone (200 microM), and 2-bromo (diglutathion-S-yl)hydroquinone (400 microM) and prior to other indices of toxicity. The ability of the cells to repair DNA damage was evident by the decrease in the extent of single strand breaks following removal of 2-bromo-3 (glutathion-S-yl)hydroquinone from the incubation medium. Moreover, inhibition of poly(ADP-ribose)polymerase with 3-amino-benzamide (10 mM), following exposure of LLC-PK1 cells to 0.5 mM 2-bromo-6-(glutathion-S-yl)hydroquinone or 2-bromo (diglutathion-S-yl)hydroquinone, decreased cytotoxicity, indicating that DNA repair processes, activated in response to DNA damage, exacerbate toxicity. Treatment with the endonuclease inhibitor, aurintricarboxylic acid did not decrease cytotoxicity. A decrease in the cytotoxicity caused by 2-bromo-6 (glutathion-S-yl)hydroquinone and 2-bromo-(diglutathion-S-yl)hydroquinone was observed when cells were incubated with catalase or pretreated with deferoxamine (10 mM). The data suggest a mechanism whereby the conjugates generate hydrogen peroxide, and the subsequent iron-catalyzed generation of hydroxyl radicals causes DNA fragmentation and cytotoxicity. PMID- 7793986 TI - Purification and characterization of an NADH-hexacyanoferrate(III) reductase from spinach leaf plasma membrane. AB - Plasma membranes were purified from spinach (Spinacea oleracea L.) leaves by aqueous two-phase partitioning. The NADH-hexacyanoferrate(III) reductase was released from the membrane by Chaps solubilization and purified 360-fold by ion exchange chromatography followed by affinity chromatography and size-exclusion chromatography on FPLC. A major band of 45 kDa and a minor contaminant of 66 kDa were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). The band at 45 kDa cross-reacted with antibodies raised against an NADH hexacyanoferrate(III) reductase from potato tuber microsomes. The native size of the enzyme was 160 kDa as determined by size-exclusion chromatography indicating that it is a tetramer. Two-dimensional gel electrophoresis, isoelectric focusing, followed by SDS-PAGE revealed three main bands of identical molecular weight with pI of 5.3-5.6. The enzyme contained about one flavin adenine dinucleotide (FAD) per 45-kDa subunit as determined by fluorescence spectroscopy, was specific for the beta-hydrogen of NADH, preferred NADH over NADPH as electron donor, and preferred hexacyanoferrate(III) as electron acceptor, e.g., it reduced Fe3+-EDTA, cytochrome c, oxygen, and duroquinone at < 10% of the rate with hexacyanoferrate(III). p-Chloromercurobenzoate, mersalyl, and dicumarol inhibited the activity by > 70% whereas FAD, flavin mononucleotide, duroquinone, and ubiquinone0 did not affect the activity. PMID- 7793987 TI - Brain mitochondrial cytochromes P450: xenobiotic metabolism, presence of multiple forms and their selective inducibility. AB - The capability of rat brain mitochondria to metabolize a variety of xenobiotics was examined. The presence of cytochrome P450 (P450) and associated monooxygenase activities were estimated in isolated rat brain mitochondria and compared with the corresponding activities in microsomes. Total P450 content in brain mitochondria from naive rats was twice that of the corresponding microsomal level. The ability of brain mitochondria to metabolize the potent carcinogen N nitrosodimethylamine was more than twofold that of the corresponding microsomal activity, while the 7-ethoxycoumarin-O-deethylase activity was significantly lower in mitochondria. Immunoblot experiments using antisera to purified rat liver microsomal P450s, namely P450 (2B1/2B2), P4501A1, and P4502E1, and purified phenobarbital-inducible rat brain P450, revealed the presence of immunoreactive bands in isolated brain mitochondria. These various antibodies to P450 inhibited the brain mitochondrial monooxygenase activities to significant, though varying extent. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450 associated monooxygenase activities, although it completely inhibited the corresponding microsomal activities. Chronic ethanol administration resulted in twofold induction of total P450 content and the monooxygenase activities known to be mediated by P4502E1, such as N nitrosodimethylamine-N-demethylase and p-nitrophenol hydroxylase in brain mitochondria. Pretreatment of animals with phenobarbital resulted in the induction of aminopyrine N-demethylase activity in brain mitochondria. The study demonstrates the presence of multiple forms of P450 in the rat brain mitochondria, their inducibility, and their capability to metabolize xenobiotics. PMID- 7793988 TI - Differential binding of vascular cell-derived proteoglycans (perlecan, biglycan, decorin, and versican) to the beta-amyloid protein of Alzheimer's disease. AB - Previous studies have demonstrated the immunolocalization of perlecan, a specific heparan sulfate proteoglycan, to the beta-amyloid protein (A beta)-containing amyloid deposits within the walls of blood vessels (i.e., congophilic angiopathy) in Alzheimer's disease (AD) brain. In the present investigation, the differential binding of previously characterized endothelial cell (EC)- and smooth muscle cell (SMC)-derived PGs to A beta was examined to determine whether the accumulation of A beta in cerebrovascular amyloid deposits may be due to its interactions with perlecan. Pretreatment of AA amyloidotic splenic and liver tissue sections with synthetic A beta (1-28) produced strong immunoreactivity with A beta antibodies at tissue sites enriched in perlecan which was partially removed by pretreatment with heparitinase, but not by chondroitin ABC lyase. [35S]-Sulfate labeled proteoglycans (PGs) derived from cultured ECs and SMCs bound to affinity columns containing A beta (1-28) or (1-40), with virtually no binding to A beta (40-1) (reverse peptide), beta-amyloid precursor protein (410-429), or bovine serum albumin. Characterization of EC and SMC PGs bound to A beta (1-28) revealed strong binding by perlecan, weak binding by decorin and biglycan, two dermatan sulfate proteoglycans, and lack of binding by versican/PG-M, a large chondroitin sulfate proteoglycan. Binding of 125I-labeled perlecan to A beta (1-28) was strongly inhibited by isolated perlecan and to a lesser extent by heparin, but not by chondroitin-6-sulfate or unsulfated dextran sulfate. Heparitinase treatment decreased, but did not eliminate the binding of 125I-labeled perlecan to A beta (1-28). Scatchard analysis of the interaction of A beta (1-28)- and EC derived perlecan in solid-phase assays indicated high-affinity (Kd = 8.3 x 10( 11) M) and lower-affinity (Kd = 4.2 x 10(-8) M) binding sites, with approximately 1 mol of perlecan binding 1.8 mol of A beta. A significant decrease in binding of EC-derived perlecan to A beta (1-28) was observed when a sequence within the putative heparin-binding motif of A beta (His13His14Gln15Lys16) was replaced by the uncharged peptide sequence, Gly13Gly14Gln15Gly16, indicating a perlecan binding site on A beta near the postulated alpha-secretase site (at Lys-16). Overall, the results indicate that specific vascular cell-derived PGs differentially interact with A beta, and that the interactions of highest affinity occur between A beta and binding sites on both the core protein and glycosaminoglycan chains of perlecan.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7793989 TI - Characterization of hormonogenic sites in an N-terminal, cyanogen bromide fragment of human thyroglobulin. AB - We have confirmed the observation of Marriq et al. (FEBS Lett. 207, 302-306, 1986) that substantial thyroxine formation occurs on enzymatic iodination of a 171-residue, N-terminal cyanogen bromide (CNBr) fragment of human goiter thyroglobulin. Marriq et al. concluded from their studies that Tyr130 is the donor for the preferential hormonogenic acceptor site Tyr5. However, in the present study we observed that thyroxine formation in the CNBr fragment occurred not at Tyr5, but rather at Tyr130. Moreover, we did not confirm the report of Marriq et al. that formation of thyroxine in the iodinated CNBr fragment involves cleavage of the Val129-Tyr130 bond. Our finding of thyroid hormone at Tyr130 was unexpected, as Tyr5 is known to be the major site of hormone formation in thyroglobulin isolated from the thyroids of humans and other mammals. In the CNBr fragment, however, Tyr5 appeared to act as a donor rather than an acceptor. Thus, while we have confirmed the finding that the N-terminal CNBr fragment of human goiter thyroglobulin is by itself capable of efficient thyroxine formation when enzymatically iodinated in vitro, we observed that the role of specific tyrosines in the hormone-forming process was different from that in intact thyroglobulin. We question, therefore, whether the CNBr fragment is a valid model for defining the role and location of hormonogenic sites in intact thyroglobulin. PMID- 7793990 TI - [Gene diagnosis of cancer]. AB - Recently, many DNA alterations have been reported in most of cancers. Now, gene diagnosis of cancers becomes a hot topic. There are at least three kinds of cancer-related genes, oncogenes, tumor suppressor genes and DNA mismatch repair genes. In hereditary tumors, gene diagnosis is particularly important, because it is possible to find predisposing individuals even before the appearance of cancers. Of course, gene diagnosis is also very useful for nonhereditary tumors. A very small numbers of cancer cells in blood, sputum, urine and stool can be detected by the highly sensitive PCR (polymerase chain reaction) technique. Prognosis may also be predicted from specific gene alterations in cancers. PMID- 7793991 TI - [Endoscopic mucosal resection for radical treatment of esophageal cancer]. AB - Clinico-pathological results of patients with superficial esophageal cancer was reviewed to determine the indications of endoscopic mucosal resection (EMR) for esophageal cancer as a radical treatment and to evaluate clinical results of EMR. The analysis on eighty-seven cases with superficial esophageal cancer who underwent esophagectomy revealed no lymph node metastasis in any 0% of case with cancer confined to the lamina propria mucosae, 10% of cancer reaching the muscularis mucosae and 43% of cancer infiltrating the submucosa. These results suggested that the endoscopic mucosal resection should be indicated for patients with esophageal cancer confined to the lamina propria mucosae. The accuracy rate for estimating depth of invasion of mucosal cancer of the esophagus was 96%. We early established "the double channel technique" for resection of mucosal lesion of the esophagus with a major part of the submucosa, we used it for sixty-nine cases, and all were eventually discharged. Immediate complications of EMR were noted in 12.9% of all cases (mediastinal emphysema: 2.9%, ulcer bleeding: 10%) and the late complication in 7.2% (esophageal stricture due to scar formation: 5.8% and ulcer bleeding 5 days after EMR: 1.4%). All cases who developed stricture had mucosal defect over 3/4 the circumference. The cumulative 5-year survival rate of patients with esophageal mucosal cancer treated by EMR (86%) showed no significant difference from those treated by esophagectomy (83.2%). We to conclude that endoscopic mucosal resection is indicated for the patient with mucosal cancer confined to the lamina propria mucosae. One can expect an excellent prognosis by less invasive treatment than esophagectomy. PMID- 7793992 TI - [Progress in surgical treatment of carcinoma of the intrathoracic esophagus]. AB - In the past 20 years, 403 patients with thoracic esophageal carcinoma underwent radical surgery. The aim of this study was to determine whether extended lymph node dissection improved the prognosis of these patients. All of the patients were divided into 4 groups every 5 years from group A to group D. Group A (n = 39) underwent radical esophagectomy with lower mediastinal and abdominal lymphadenectomy by the left thoracoabdominal approach. Majority cases in Group B (n = 94) also underwent radical esophagectomy with right upper, lower mediastinal and abdominal lymphadenectomy (incomplete 2-field dissection) by the right thoraco-abdominal approach. About 40% cases in Group C underwent radical esophagectomy with extended cervicothoraco-abdominal lymph node dissection (3 field dissection) and almost all of the others had radical esophagectomy with 2 field dissection. About 60% of the cases in group D underwent radical esophagectomy with 3-field dissection and the majority of the others had complete 2-field dissection (i.e.) radical lymphadenectomy around bilateral upper, lower mediastinal and abdominal lymph nodes. The five-year survival rate was 21% in group A, 23% in group B, 37% in group C and 55% in group D. The survival curve was improved according to the extent of lymph node dissection. Especially significant improvements of survival rate were found in group C and D compared with those in group A and B. Furthermore, group D showed significantly better survival than that of group C. Complete 2-field and 3-field dissection resulted in a better prognosis than incomplete 2-field dissection, while no significant difference in prognosis was found between complete 2-field and 3-field dissection. However, neither 2-field nor 3-field dissection resulted in improved prognosis in cases involving 7 or more positive lymph node metastases. These results suggest that radical esophagectomy and lymph node dissection involving bilateral upper mediastinal area are important factors to improve postoperative prognosis in patients with thoracic esophageal carcinoma. However, more effective adjuvant therapy is needed for the patients with many positive node metastases. PMID- 7793993 TI - [Current status of radiotherapy for esophageal carcinoma]. AB - Preoperative radiotherapy for esophageal carcinoma had no improvement on survival or locoregional control. The role of postoperative radiotherapy is limited to patients with residual tumor. According to the nationwide statistics of the results of radiotherapy alone, 5-year survival rate of superficial or Ep-Sm type was 26% and 32.5%, respectively. Intracavitary irradiation will improve not only survival but provide palliation of dysphagea. Now, it must be discussed the usefulness of radiotherapy from the viewpoint of cost-benefit ratio. PMID- 7793994 TI - [Local chemotherapy by a sustained-release preparation with fibrin seal against the operative wound in head and neck cancer]. AB - Fibrin seal has been used for hemostasis and sealing in operative field of tumors in the head and neck. The authors applied it for drug preparation and tried a local chemotherapy to treat residual and disseminated tumors of cellular level in the operative wound using 5-FU. The drug release rate in this therapy in vitro study was 50% after 24 hrs. When injected to rats bearing Yoshida sarcoma, it exhibited a marked antitumor effect compared to the control group given 5-FU alone. This therapy is easy to make the dosage adjustment and can apply drugs directly to the tumor residue at the high concentration. It will be clinically a useful adjuvant therapy for radiotherapy, surgery or chemotherapy. PMID- 7793996 TI - [A cooperative late phase II trial of l-leucovorin and 5-fluorouracil in the treatment of advanced gastric cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)]. AB - A multicenter cooperative study was conducted to evaluate the clinical efficacy of l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 69 cases of advanced gastric cancer. l-LV was administered intravenously by a 2-hour infusion at a dosage of 250 mg/m2 and 5-FU at a dosage of 600 mg/m2, intravenously via bolus one hour after administration of l-LV had been started. The combination was given weekly for 6 weeks followed by a 2-week rest period. Patients were evaluated for response after the sixth dose. Nineteen PRs were noted in the 55 patients for an overall response rate of 34.5%. Median survival time was 190 days for eligible cases, and 448 days for PR cases. Age and performance status (PS) appeared to influence clinical response. Patients aged 49 years or younger showed a significantly higher PR rate than those aged 50 years or older. The PR rate was significantly higher in the patients of PS 0-1 than those of PS 2. Diarrhea and leukopenia were experienced in 46.7% and 65% of patients, respectively. Patients who had severe toxicities required discontinuity of treatment. After recovery, treatment was repeated. The clinical results are promising for patients with advanced gastric cancer, particularly middle-aged patients. However, whether the l-leucovorin and 5-FU combination therapy will ultimately produce superior results in middle-aged patients awaits the results of Phase III trials. PMID- 7793995 TI - [Pilot study of irinotecan in refractory small cell lung cancer]. AB - Sixteen patients with refractory small cell lung cancer (SCLC) were treated with an irinotecan starting dose of 100 mg/m2 given as a 90-minute iv infusion every week with subsequent doses based on toxicity. Mean age was 64 years; 14 male and 2 female; 4 with limited disease and 12 with extensive disease; all patients pretreated with combination chemotherapy containing etoposide. The overall response rate was 50% (95% CI 25-75%) with no CR and 8 PR. The median duration of response was 46 days. Major toxicities were leukopenia, diarrhea and pulmonary toxicity. Irinotecan was thus an effective agent in refractory SCLC. PMID- 7793997 TI - [Quality of life in patients with advanced gastric cancer receiving AO-90, a methionine-free intravenous amino acid solution, with 5-fluorouracil and mitomycin C]. AB - We conducted a randomized, multicenter, controlled trial of AO-90, a methionine free 7.43% intravenous amino acid solution, in patients with advanced recurrent gastric cancer. The regimen used in the study was comprised of two-week treatment cycles, with a withdrawal period between cycles. During treatment, patients were given either AO-90 (500-750 ml/day; AO/MF group) or a commercial amino acid solution (600-800 ml/day; C/MF group) by total parenteral nutrition (TPN) for 14 days concomitantly with MF therapy (5-fluorouracil 350 mg/m2/day, iv continuously for 14 days and mitomycin C 7 mg/m2, iv push on days 7 and 14). We interviewed 118 eligible and evaluable patients (72 men and 46 women; 59 cases in the AO/MF group and 59 in the C/MF group) about their quality of life immediately before the start of treatment, one week and two weeks after the start of treatment, and one week and two weeks after treatment. A 11-item questionnaire was used to interview the subjects: nine questions using a five-point scale, one question using a 100-mm linear visual analog scale, and one question using a five-grade face scale. Changes in the grades compared with baseline data were scored as 1 point (improvement of one grade or more, or 20 mm or more), 0 points (no changes), and-1 point (decline of one grade or more, or 20 mm or more). Before analyzing the significance, quality of life score data were adjusted by the Mantel-Haenszel method due to uneven distribution of subjects concerning baseline performance status and complications. Among the items questioned, subjects receiving AO-90 showed significantly higher scores in appetite, nausea, and ambulation at some evaluation time points than those receiving a methionine containing TPN. The results show that AO-90 improved the quality of life of patients with advanced recurrent gastric cancer. PMID- 7793998 TI - [A late phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)]. AB - A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma. PMID- 7793999 TI - [Retrospective analysis of postoperative chemotherapy with UFT against pancreatic cancer]. AB - The retrospective study was carried out to evaluate the effect of UFT given orally in patients with histologically proven pancreatic cancer in our institutions for 6 years. The study regimen was designed as follows: 400 or 600 mg/body UFT per day after the patients having something solid evidences of tumor. For 6 years, 78 patients were entered in this protocol. Further details of the patients characteristics were as follows: head 47 (60.3%) cases, tail & body 31; resection cases 26 (33.3%), palliative 52; Stage IV 62 (79.5%) cases. Resection, P (peritoneal dissemination). H (liver metastasis) and T (tumor size) were statistically proven to be significant prognostic factors. The median survival time of UFT group was 204 days and that of non UFT group was 123 days. According to the retrospective analysis, there was a significant difference in the cumulative survival rate between UFT group and non UFT group with 1.98 of Hazard's proportional ratio (p = 0.009). However, further clinical investigations prospective study are necessary to confirm these data. PMID- 7794000 TI - [Essential thrombocythemia transformed to minimally differentiated acute myeloid leukemia]. AB - A 64-year-old female diagnosed for essential thrombocythemia was treated with MCNU 50 mg four times in the course of the disease. Six months after the last administration, in May 1991, she was admitted because of decreasing thrombocyte count and appearance of blasts in the peripheral blood. On admission, laboratory findings were as follows: WBC 700/microliters with 5% of blasts, RBC 331 x 10(4)/microliters, and PLT 17.9 x 10(4)/microliters. Bone marrow aspiration revealed hypocellular marrow with 39% blasts. About 5% of the blasts were positive for myeloperoxidase by electron microscopy analysis. Leukemic cells were positive for CD 7, 13, 33 and 34, negative for other lymphoid lineage markers, and demonstrated no rearrangement of TCR-beta, gamma and IgH genes. Although she was treated with low-dose cytosine arabinoside, no response was observed. Subdural hematoma and sequential pneumonia developed and the patient died eight months after leukemic transformation. In conclusion, we think that the leukemic transformation might have been developed in the natural course of essential thrombocythemia in the present case. However, we cannot exclude the influence of MCNU. PMID- 7794001 TI - [Refractory anemia with excess myeloblast in transformation induced remission by combined oral administration of cytarabine ocfosfate and 6-mercaptopurine]. AB - A 55-year-old female presented with sore throat and slight fever. The patient was admitted to our hospital on December 13, 1993. Full blood count showed hemoglobin 10.7 g/dl, white cell count 960/microliters (neutrophils 14%, lymphocytes 82%, blasts 2%) and platelets 13,000/microliters. Bone marrow examination showed hypocellularity with 4.5% of myeloblast positive for peroxidase. The bone marrow specimens on Dec. 20 showed 15.5% of myeloblasts, some of which had Auer rods. These findings led to the diagnosis of refractory anemia with excess myeloblast in transformation (RAEB-T) of French-American-British Cooperative Group. The patient was transfused and treated with cytarabine ocfosfate (SP-AC) (100 mg tid) and 6-mercaptopurine (50 mg tid) for 14 days. During chemotherapy she complained of nausea and anorexia, but they were managed easily with medication. On Feb. 7, 1994, forty-two days after the start of administration, peripheral blood and bone marrow aspirate were compatible with a complete remission. Although complete remission was sustained with courses of chemotherapy for 4 months, relapse occurred and the patient died of septicemia on August 29, 1994 after induction failure. Observation suggested that oral SPAC in combination with 6 mercaptopurine had a good antileukemic effect on the myelodysplastic syndrome. However, the duration response was short, and further improvement of the therapy is needed. PMID- 7794002 TI - [Neoadjuvant chemotherapy of liver tumors metastasized by sigmoid colon cancer: a case report of CDDP/5-FU intraarterial infusion therapy followed by hepatectomy]. AB - A case of liver tumors metastasized by Sigmoid colon cancer was treated with intrahepatic arterial infusion of CDDP (10 mg) and 5-FU (250 mg) via subcutaneously implanted reservoir. After 20 administrations of CDDP and 5-FU, the tumors in the right lobe of the liver disappeared, but those in the left lobe remained. Therefore left hepatectomy was carried out. Six months after the hepatectomy, a nodule recurrence was disclosed in the right lobe of the liver. With re-elevated serum CEA level, subsequent intrahepatic arterial infusion of CDDP and 5-FU the nodule size reduced with normalization of the serum CEA level. PMID- 7794003 TI - [Effects of 5-fluorouracil in shrinking residual gastric cancer: a case report]. AB - The patient was a 79-year-old man who underwent extensive gastrectomy and Billroth-II reconstruction for gastric ulcer in 1974. He complained of heartburn in November, 1992, and endoscopy for the residual stomach revealed IIb + IIa-like lesion mainly in the posterior wall of the anastomosed site, which was diagnosed as well differentiated adenocarcinoma. As the patient refused to be operated, 150 mg/day of 5-FU was administered. For 4 months before he decided to undergo operation, 12.9 g of 5-FU was administered in total. After rehospitalization, endoscopy of the residual stomach showed shrinkage of the lesion, and biopsy revealed no malignant findings. The pathological examination after total resection of the residual stomach showed atypism, but no evidence to support malignancy. He has continued to be well without sign of recurrence for 1 year since the operation. The administration of 5-FU is widely used as preoperative adjuvant chemotherapy. This case it is rare for 5-FU to cause the disappearance or falling off of malignant cells. PMID- 7794004 TI - [Pilot study of sequential chemotherapy and radiation therapy using of liniac and fast neutron for limited small cell lung cancer]. PMID- 7794005 TI - [Biochemically modulated chemotherapy with high-dose L-leucovorin and 5 fluorouracil for multiple liver metastasis from colorectal cancer]. PMID- 7794006 TI - [Ifosfamide-induced hemorrhagic cystitis and its prevention by mesna]. PMID- 7794007 TI - [Liver tumor targeting of drugs: Spherex, a vascular occlusive agent]. AB - Embolizing chemotherapeutic methods are presently used primarily for nonresectable metastatic hepatic carcinoma. Because this kind of carcinoma is generally ischemic, little is expected from embolizing chemotherapeutic methods aimed at tumor necrosis by blood flow obstruction using gelatin sponges. On the other hand, since the arrival rate of Lipiodol is not very good, embolizing chemotherapeutic therapy employing Lipiodol is not expected to be very effective. Consequently, therapies against metastatic hepatic carcinoma have mainly been intraarterial chemotherapies without embolization. Spherex is a transient embolization agent prepared by suspending 60 mg/ml of degradable starch microspheres (hereinafter, DSM) in physiological saline. It was developed by Pharmacia AB, Sweden, as an arterial embolizing agent for embolizing chemotherapy, and it was the first agent approved for use in Japan as an embolization material. DSM is composed of spherical particles approx. 45 microns in diameter prepared by crosslinking partially hydrolyzed potato starch using epichlorohydrin as a crosslinking agent, and it is characterized by gradual decomposition by blood amylase, having a half-life of 20-35 minutes in vitro. Clinically, when Spherex is administered via the arteries, embolization has been found to occur in the arterioles. Furthermore, administration of Spherex via the hepatic artery in combination with an anticancer drug results in the formation of transient reduction of bloodflow, thus making it possible to extend the period of retention of the anticancer drug at a high concentration in the tumorous region. As a result, the local antitumor effect of the anticancer drug may be reinforced, with alleviation of systemic side effects. In clinical tests involving its administration to metastatic hepatic tumors in combination with mitomycin C (hereinafter, MMC), the efficacy is 54.5% with arterial injection therapy with Spherex, which is significantly superior to the 20.0% obtained with arterial injection of MMC alone. Although the rate of side effects exhibited, including pain, digestive symptoms and fever, has been significantly higher in combination with Spherex, myelosuppression indicated by abnormal fluctuations in leukocyte and platelet counts was found to be greater with administration of MMC alone, suggesting its value as an effective future therapy for metastatic hepatic carcinoma. These data indicate that Spherex is not expected to yield an antitumor effect due to long-term blood flow obstruction in the hepatic artery, an effect associated with gelatin sponges heretofore used for embolizing chemotherapy. Instead, it causes a transient occlusion upon one-shot intraarterial injection therapy with MMC, thus extending the retention time of MMC at high concentration in tumorous sections, thereby yielding a high local antitumor effect with MMC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7794008 TI - [Prognostic factors of hepatocellular carcinomas after non-surgical treatment]. AB - We studied 710 patients with hepatocellular carcinoma(HCC) who underwent non surgical treatment. Multivariate analysis demonstrated that four factors, the number of tumors, tumor size, portal vein tumor thrombus and the severity of liver dysfunction (Child's classification) before treatment were found to be significant for the prognosis of patients and that severity of liver dysfunction was the most significant factor. of 179 patients with small HCC who underwent percutaneous ethanol injection (PEI), the severity of liver dysfunction was the most significant factor contributing to the prognosis. The prognosis of HCC is influenced by many factors. We conclude that early detection of tumors followed by early therapy is the most important. PMID- 7794009 TI - Modelling and monitoring organochlorine and heavy metal accumulation in soils, earthworms, and shrews in Rhine-delta floodplains. AB - In the Rhine-delta, accumulation of microcontaminants in floodplain foodwebs has received little attention in comparison with aquatic communities. To investigate organochlorine and metal concentrations in a terrestrial foodchain, samples of soil, earthworms (Lumbricus rubellus), and shrew (Crocidura russula, Sorex araneus) livers and kidneys were taken from two moderately to heavily polluted floodplains. Chlorobiphenyl residues in earthworm fat were 0.10 to 3.5 times the concentrations in soil organic matter, whereas ratios for other organochlorines varied between 0.87 and 8.8. These ratios are one order of magnitude lower than expected from laboratory experiments with earthworms, and laboratory and field studies on aquatic invertebrates. Bioconcentration ratios for heavy metals are in accordance with literature values for other locations, confirming the high potential for cadmium accumulation in Lumbricidae. Concentrations of organochlorines in shrew liver lipids were 1.0 to 13 times the residues in earthworm fat. These values are higher than lipid-corrected biomagnification ratios for laboratory rodents, but equal to those measured for benthivorous birds in the Rhine-delta. On a dry weight basis, kidney-earthworm ratios for cadmium were about one order of magnitude lower than previously reported values for insectivores. Soil concentrations of many compounds in both floodplains did not meet Dutch quality standards. Yet, hexachlorobenzene, chlorobiphenyl 153 (PCB153), gamma-hexachlorocyclohexane, sigma DDT, and dieldrin residues in earthworms and shrews did not exceed diet levels expected to be safe for endothermic species. An exception was noted for cadmium in worms and shrew kidneys. Heavy metal pollution in soil was close to levels that are critical to earthworms in laboratory studies. Cadmium concentrations in shrew kidneys were below levels suggested to be safe for Sorex araneus, but above those that were critical to the rat. PMID- 7794010 TI - Contaminant levels in harbor seals from the northeastern United States. AB - The concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzofurans (PCDF), polychlorinated dibenzo-p-dioxins (PCDD), and mercury (Hg) were determined in blubber and liver tissues of harbor seals (Phoca vitulina) collected along the northeast coast of the U.S. Average PCB concentrations in seal blubber (sum of congeners) were 12.0 micrograms/g (wet weight) with a range of 7.30 to 24.3 micrograms/g in 1980 and 6.66 micrograms/g (wet weight) with a range of 2.61 to 11.3 micrograms/g in 1990-1992. Comparisons between blubber data from this study and previous work indicated that the concentration of PCBs along the northeast coast of the U.S. may have decreased over the past twenty years. The average p,p'-DDE concentrations in seal blubber were 10.9 micrograms/g (wet weight) in 1980 with a range of 6.95 to 21.9 micrograms/g and 4.12 micrograms/g (wet weight) with a range of 1.83 to 7.84 micrograms/g in 1990-1992. Only trace amounts of PCDFs and PCDDs were found in a few blubber samples; levels in most tissues were below detection (3-5 pg/g) (wet weight). Trace amounts (< 30 ng/g) of phenanthracene, anthracene, and alkylated MW-178 compounds were found in some seal samples; all other PAH compounds were below the detection level (5-15 ng/g). Toxic equivalents (TEQ) of selected coplanar and mono-ortho PCB congeners and relative toxic equivalents (RTE) (pg total TEQ/microgram total PCB) were calculated, using recently proposed dioxin toxic equivalent factors (Ahlborg et al. 1994). The TEQs ranged from 41 to 315, and the RTEs ranged from 2.25 to 16.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794011 TI - Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers. AB - The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toluene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples. At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820. From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794012 TI - Modulation of the adherence of human polymorphonuclear leukocytes by cadmium and nickel: sexual differences. AB - The effect of cadmium (xenobiotic element) and nickel (ultra-trace bioelement) on the adherence to plastic of peripheral polymorphonuclear leukocytes (PMNs) from male (M-PMNs) and female (F-PMNs) donors was analyzed. Exposure of PMNs to either metal stimulated adherence, mainly the early adherence (8 min). A sex influence on the adherence was observed. Up to 45 min of incubation, M-PMNs adhered more than F-PMNs. This sexual dimorphism also took place in the case of metal stimulation. Cadmium and nickel enhanced early spontaneous adherence of cells from either sex, but only the late adherence (25 min) of F-PMNs. The adherence stimulation was generally greater in F-PMNs, but M-PMNs achieved higher adherence levels. Nickel was more effective than cadmium in enhancing the adherence, especially the early adherence of F-PMNs. PMID- 7794013 TI - Isomer-specific analysis of polychlorinated biphenyls and 2,3,7,8 tetrachlorodibenzo-p-dioxin equivalents (TEQs) in red fox and human adipose tissue from central Italy. AB - The general exposure of humans and foxes to polychlorinated biphenyls (PCBs) and DDT in Italy was determined by analysis of adipose tissue samples collected from 1991-1992. sigma PCB concentrations varied between 1.0 and 2.6 micrograms/g (wet wt.). sigma DDT concentrations ranged from 1.6 to 5.0 micrograms/g (wet wt.). About thirty-five PCB congeners were identified in most samples. PCB congeners of IUPAC Nos. 138, 153, and 180 were the most abundant compounds, accounting for an average of 50% of the sigma PCBs in humans and 64% in foxes. Generally, higher chlorinated biphenyls and those with a 2,4,5-chlorine substitution in one ring and at least one substitution in the 4-position of the other ring were preferentially accumulated. Coplanar PCB congeners were detected at considerable concentrations and there is no sign of decline in their concentrations with respect to previously reported data. IUPAC Nos. 118, 156 and 126 were the main contributors to toxicity in humans and foxes. The significant contribution of mono-ortho congeners in humans and non-ortho congeners in foxes suggests that differences in metabolic potential may affect the PCB toxicity pattern. PMID- 7794014 TI - Postmortem tissue levels of polychlorinated biphenyls in female rhesus monkeys after more than six years of daily dosing with Aroclor 1254 and in their non dosed offspring. AB - Polychlorinated biphenyl (PCBs) analyses were made on prenecropsy blood samples and postmortem adipose, liver, kidney, and brain tissues from female rhesus monkeys fed a daily dose of 0, 5, 20, 40, or 80 micrograms Aroclor 1254/kg body weight for approximately 6 years. During this time, the females were bred with non-dosed males. All resulting offspring were nursed for 22 weeks and fed no additional PCBs until they were necropsied at approximately 120 weeks after birth. PCBs were also measured in necropsied infant tissues to determine PCB levels due to intake of PCB-contaminated milk from the dosed dams, in addition to in utero exposure. Polychlorinated biphenyl levels in all tissues of the adult monkeys increased with their dosage. The highest PCB levels were found in adipose tissue and the lowest levels were found in the brain. Polychlorinated biphenyl residues in the cortex of the kidney were lower than in the medulla, while in the brain no appreciable differences were observed between the occipital and frontal lobes. Necropsy tissues of infants from dosed dams contained more PCBs than those nursed by controls, but less than tissues from stillborn infants. Although no differences were observed between PCB tissue levels from monkeys having offspring and those having no offspring, those having a stillborn infant had higher PCB levels in their tissues than those with a viable infant. Similarly, monkeys that were euthanized because of poor health had higher PCB levels in their tissues than those necropsied at the conclusion of the study and showed a dramatic shift from tetra- and hexachlorobiphenyls to penta- and heptachlorobiphenyls in their tissues. The PCB distribution pattern in tissues from a dosed mother/infant pair differed considerably. A larger percentage of heptachlorobiphenyls was found in the infant than in its dam. The adipose/blood PCB ratio in the adult monkeys remained remarkably constant. PMID- 7794015 TI - Toxicological potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to 100 other compounds: a relative potency analysis of in vitro and in vivo test data. AB - A common definition of relative potency is the dose of a reference compound required to cause a particular incidence of a specific toxic response divided by the dose of a test compound needed to cause an equal incidence of that same effect. In this simple manner, toxicological assessments for a chemical of concern can be made in terms of another compound about which much is known from a human health perspective. Relative potency factors were used to compare 2,3,7,8 tetrachlorodibenzo-p-dioxin CAS # 1746-01-6 (TCDD) with 100 other compounds both individually and collectively. All results were standardized to a common scale that spanned many orders of magnitude and was indexed to an arbitrary potency of unity for benzo(a)pyrene [B(a)P]. From comparisons between 2,771 pairs of bioassay results (i.e., matched experimental design conditions) for TCDD compared with the 100 other compounds, it was found that TCDD is about 600 times as toxic as B(a)P (interquartile range of 130 to 1,900). The distribution of relative potency values is fitted accurately with a log-normal distribution function having an untransformed mean of 550 and an untransformed slope (i.e., the inverse of the standard deviation of the distribution) of 140. These factors combined with (a) a reference lifetime carcinogenic risk level of 1/100,000 and (b) a universal, potency-dependent risk coefficient (estimated from the collection of epidemiologically-based carcinogens) yielded estimates that equally toxic concentrations for TCDD should be in the range of 13 pg/m3 and 7 pg/L in air and water, respectively. PMID- 7794016 TI - Chronic accumulation of cadmium in the edible tissues of Oreochromis aureus (Steindachner): modification by mercury and lead. AB - The influence of mercury and lead on cadmium accumulation was investigated by exposing the fish Oreochromis aureus, or Blue Tilapia, to two heavy metals simultaneously. The chronic accumulation profile of cadmium in the liver, brain, gill filaments, intestine, caudal muscle, spleen, trunk kidney, and gonads was determined for exposure to cadmium alone and with lead or mercury. O. aureus was exposed to cadmium alone at 0.05 and 0.10 mg/L, and mixtures of 0.05 mg/L cadmium with 0.05 mg/L mercury or lead (0.05 and 0.50 mg/L). Little research has previously been carried out on the long-term interaction between these heavy metals and their effects on tissue accumulation of heavy metals. In a food fish such as O. aureus, a knowledge of toxic metal accumulation patterns is of great importance. The highest levels of cadmium were consistently accumulated by the kidney, and the presence of other mercury or lead did not change this trend. The spleen, intestine, and liver also accumulated high levels of cadmium, while the caudal muscle and brain accumulated the lowest levels of cadmium. Separating the viscera from the muscle would therefore reduce the cadmium burden of fishmeal. PMID- 7794017 TI - Quantitative structure-toxicity relationships and volume fraction analyses for selected esters. AB - The acute toxicity of aliphatic and aromatic mono and diesters in two eucaryotic organisms was compared. The test systems were the static 2-d Tetrahymena pyriformis 50% population growth impairment (IGC50(-1)) assay, and the flow through 4-d Pimephales promelas 50% mortality (LC50(-1)) assay. In ciliates, esters act via the nonpolar narcosis mechanism of toxic action. This was indicated by: the high quality 1-octanol/water partition coefficient (log Kow) dependent quantitative structure-activity relationship (QSAR), log IGC50(-1) = 0.79 (log Kow) - 1.93, n = 15, r2 = 0.945, s = 0.22, f = 222.37 Pr > f = 0.001); volume fraction (Vf) (0.8e-02); and "a" coefficient (0.3) which are not different from other nonpolar narcotics. In vivo hydrolysis in Tetrahymena appears to be insignificant. However, in fish, presumably because of more active esterases, in vivo hydrolysis is significant and leads to greater toxicity of esters than observed for nonpolar narcotics. Moreover, it leads to a unique high quality QSAR, log LC50(-1) = 0.64 (log Kow) - 0.64, n = 14, r2 = 0.945, s = 0.22, f = 207.08, Pr > f = 0.0001). Due to in vivo hydrolysis, a nonreducing concentration gradient is formed between water and fish. Therefore, the fish take up more toxicant as compared to a situation that leads to thermodynamic equilibrium. Additional information about the mechanism of ester toxicity in fish was gained by applying corrections for hydrolysis in volume fraction analyses. The corrected Vf (0.6e-02) is very close to the one found for nonpolar narcotics (0.7e 02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794020 TI - [Needle biopsy of the breast: cytopuncture with fine needle and microbiopsy of non palpable breast lesions detected by mammography]. PMID- 7794018 TI - [Quality control in anatomo-cytopathology. Breast cancer]. PMID- 7794021 TI - [Non palpable cancers of the breast. The point of view of the pathologist]. PMID- 7794019 TI - [Recommendations for the anatomopathological study of non palpable breast lesions detected by mammography]. PMID- 7794022 TI - [Breast cancer, model in biological and clinical oncology. Role of hormones and growth factors]. AB - It is shown that breast cancer can be considered as a paradigm of comprehensive cancer biology and treatment based on analysis of each individual tumor. Historically, it was first observed in breast cancer that tumor progression could be dependent on factors regulating physiological activities (i.e. hormones). It was also observed that tumor growth progressively becomes autonomous, through successive degradation of the multiple steps involved in the control of cell proliferation and differentiated activities. Hormonal treatment of breast cancer provided the first example of targetted biotherapy. The discovery of the mechanism of action of hormones via specific receptors opened the field of tumor tissue analysis to determine the main biological factors involved in tumor progression. In the near future, such data should be the best guide for selection of the most appropriate treatment in each individual case. PMID- 7794023 TI - [Predictive value of cytology for the efficacy of chemotherapy in breast cancers]. AB - For the past decade, primary chemotherapy has been extensively used in breast cancer treatment. However, valuable indicators of tumor response are needed. Fine needle cytopuncture allows the study of malignant cells by cytologic examination, image analysis and flow cytometry. Some parameters evaluated before treatment (cytologic grade, nuclear area and S phase) or at the beginning of treatment (cytomorphologic and cell kinetic changes) have been shown to be correlated with tumor response. The methods, their value and limitations, and results of the literature are discussed. PMID- 7794024 TI - [Effects of progesterone and progestational hormones on the mammary gland]. AB - The growth of the mammary gland during the active genital period depends on a delicate balance between the action of the two major female sex steroid hormones, estradiol and progesterone. The regulation of growth and maturation of the gland primarily depends on the combined action of estradiol and progesterone. Breast epithelial proliferation is maximal during the luteal phase of the menstrual cycle. While estrogen appears to be the major impetus to the proliferation of mammary cells, the effect of progestin is subject to debate. Progestins have either a positive, modest or no growth effect or may even inhibit growth. Progestins could stimulate the development of malignant cells in contrast to normal or non-malignant cells. It is difficult to extrapolate in vitro results to the human breast. There is presently no direct evidence that progestins regulate the concentration of estrogen receptors (ER) in normal breasts. Furthermore, it is possible that each type of progestin may have different effects. Most studies suggest that progestins are effective in the treatment of premenstrual syndrome and benign breast disease. The therapeutic basis for the use of progestins is the suppression of pituitary-ovarian function the reduction of the effect of estrogen on breast tissues. Whether progestins give protection against breast cancer is less clear. If they do, the mechanism is not the same as that of the endometrium [down-regulation of ER, increase of 17 beta-hydroxysteroid dehydrogenase activity (E2DH)]. High doses of oral synthetic progestins are effective in the treatment of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794025 TI - [Inflammatory cancer of the breast: review and experience at Saint-Louis hospital]. AB - Inflammatory breast cancer represents about 1 to 6% of all breast cancers. It has a sudden onset and affects women of the same age as other breast cancers. Its particular feature is the almost constant development of metastases. The 5-year survival after surgery or surgery and radiotherapy varies between 0 and 28% with a median survival of 18 months. The use of anthracycline-based chemotherapy has doubled the median survival, but has not achieved cure. Clinical research is directed towards therapeutic intensification with or without autologous bone marrow transplantation. The authors report their experience at Hopital Saint Louis. PMID- 7794026 TI - [Medullary carcinoma of the breast. What remains of this entity today?]. AB - Identified half a century ago as a favorable prognostic form, medullary breast cancer was classified by Ridolfi in 1977 as necessarily combining 5 features: seemingly wall-circumscribed histological limits, a syncytial architecture in at least 75% of the areas examined, inflammation of the stroma containing diffuse lymphocytes and plasma cells, moderate or marked anisonucleosis and absence of tubular differentiation and/or an intraductal component. Defined is this way, it only accounts for one third of breast cancers with stromal invasion and its outcome is significantly more favorable. Although the reproducibility of this classification is not perfect, only the combination of morphological features prevail over the "new" biological characteristics. PMID- 7794027 TI - [Genetics and cancer: application to the breast]. AB - Various gene systems are involved in events occurring during transformation of a normal cell into a cancer cell. By order of intervention, genes responsible for an increased individual susceptibility to cancer can be distinguished from actual cancer genes, followed by genes involved at other levels of carcinogenesis. 15 to 20% of patients with breast cancer have a first-degree relative affected by the same cancer, although an inherited predisposition to cancer is only established in 4 to 10% of cases. The genetic heterogeneity of familial forms of breast cancer make it difficult to identify susceptibility genes. At the present time, 3 regions of the genome have been implicated in the predisposition to breast cancer in women: the BRCA1 gene, the BRCA2 gene and the TP53 gene. All predisposition genes are able to transmit susceptibility due to a mutation or inherited microdeletion. PMID- 7794028 TI - [Sarcomatoid carcinoma of the breast]. PMID- 7794029 TI - [Phyllodes tumors]. AB - A review of mammary phyllodes tumors is presented. Clinical, radiological and cytological features are treated, with special emphasis on the histopathological grading system and prognostic indicators. Other analytical methods are described: immunohistochemistry, hormonal receptors study, flow cytometry and electron microscopy. A large place is also given to differential diagnosis, clinical course, histogenesis and originality of some phyllodes tumors. The authors stress the importance of wide excision and the contribution of frozen sections in surgical treatment. PMID- 7794030 TI - [Mesenchymal breast sarcomas: general review]. AB - Breast sarcomas are rare, representing 1% of all malignant breast tumors. A variety of histologies are found, the main ones being fibrosarcomas and malignant fibrohistiocytomas. Nodal involvement is rare and, as in other sarcomas, hematogenous spread of metastases is more usual. Major prognostic factors are histological grade and mitotic activity; the three-year disease-free survival ranges between 40% and 60%. Surgery remains the treatment of choice of these tumors; for some authors adjuvant irradiation could improve local control, especially for patients treated with conservative surgery. The role of adjuvant chemotherapy remains undefined. PMID- 7794031 TI - [Primary non-Hodgkin lymphomas of the breast. Focus]. AB - Although very rare (0.12 to 1.1% of all breast tumours), primary non-Hodgkin's lymphomas of the breast need to be distinguished from the group of malignant epithelial tumours, as the staging and therapeutic modalities are different, corresponding to those applied to lymphomas in general. In the majority of cases, the current techniques of aspiration cytology, needle or surgical biopsy, immunohistochemistry allow the diagnosis and typing according to the usual histological classifications. PMID- 7794032 TI - [Dermatoses of the nipple and the areola]. AB - Dermatoses of the nipple and areola are rare. The commonest dermatosis is Paget's disease, which presents in the form of a well demarcated erythematous area, sometimes erosive, oozing or hyperkeratotic. Histological examination reveals an intraepidermal proliferation of large clear cells, either isolated or grouped in clumps, predominantly in the suprabasal layers. Immunohistochemistry shows that these cells express low molecular weight cytokeratins and the epithelial membrane antigen, fairly frequently carcinoembryonic antigen. In 96% of cases, Paget's disease is associated with underlying breast carcinoma, either in situ or invasive. Erosive adenomatosis presents in the form of an erosion of the nipple, which is sometimes increased in size. Histologically, it consists of a benign tumour which may ulcerate the epidermis, composed of tubes and papillae lined by a double layer of epithelial and myoepithelial cells. The syringomatous tumour is exceptional. In places, it forms rudimentary sweat ducts and is considered to have an intermediate malignancy; its resection must be complete. Other tumours may also be observed in this site: leiomyoma, leiomyosarcoma, benign cutaneous lymphocytoma, basal cell carcinoma, naevoid areolar hyperkeratosis. They are exceptional except areolar neurofibromas in case of neurofibromatosis. Infectious dermatoses (viral warts, molluscum contagiosum, scabies) are accompanied by lesions in other sites. They same applied to the majority of inflammatory dermatoses such as eczema or Fox-Fordyce disease. Supernumerary nipples are situated on a line extending from the anterior part of the axillary crease to the medial part of the inguinal crease. PMID- 7794033 TI - [Lymphocytic plasma cell mastitis]. AB - Plasma cell mastitis is a rare form of inflammatory, non-infectious, non neoplastic, mastitis, not occurring during the post-partum and breastfeeding period. The pathogenesis of this lesion is not yet fully elucidated and an auto immune origin is currently proposed. The common feature of this form of mastitis is the possibility of evolving towards recurrent aseptic abscesses. Treatment remains difficult and relapses are frequent with fistula formation to the skin, either spontaneously, or after surgery, even involving wide excision. PMID- 7794034 TI - [Immunohistochemical evaluation of estrogen and progesterone receptors on paraffin sections of breast carcinomas. Practical thoughts based on the study of 368 cases]. AB - 368 formalin-fixed and paraffin-embedded carcinomas of the breast were studied by immunohistochemistry using antibodies to estrogen and progesterone receptors. The results, which are comparable to the results published in the literature, are discussed with particular emphasis on quality assurance parameters. PMID- 7794035 TI - Different concepts of chronic musculoskeletal pain. PMID- 7794036 TI - Imaging the swollen joint in the young patient. PMID- 7794037 TI - Magnesium whitlockite deposition in articular cartilage: a study of 80 specimens from 70 patients. AB - OBJECTIVE: To examine articular cartilage from a number of joint sites, using a large sample group, for the presence of magnesium whitlockite crystal deposition. METHODS: Articular cartilage specimens were taken from a total of 70 patients. The majority of specimens were taken from femoral heads, with smaller numbers from femoral condyle, tibial plateau, radius, ulna, and several small peripheral joints. Normal and osteoarthritic articular cartilage specimens were obtained from patients undergoing prosthesis replacement or amputation. Specimens were resin embedded and examined using transmission electron microscopy and x ray microanalysis. RESULTS: Magnesium whitlockite crystals were identified, on the basis of morphology, size and elemental composition, in articular cartilage from all sites sampled. The distribution of crystals was similar in all samples (restricted to the superficial zone), although the density of deposition was extremely variable, with the greatest density observed in femoral head specimens. No magnesium whitlockite crystals were observed in osteophytic or epiphysial cartilage. CONCLUSIONS: This study demonstrated the widespread extent of magnesium whitlockite deposition in human articular cartilage, albeit at much lower density than previously reported in femoral head articular cartilage. In consideration of possible roles for these crystals in articular cartilage, it is concluded that an opportunistic mode of formation, possibly influenced by mechanical stresses, would be most plausible. PMID- 7794038 TI - Identification and functional importance of plasma kallikrein in the synovial fluids of patients with rheumatoid, psoriatic, and osteoarthritis. AB - OBJECTIVES: To determine and identify, unequivocally, if plasma kallikrein (PK) is present in the synovial fluid of patients with rheumatoid (RA), psoriatic (PA) and osteo (OA) arthritis, and to consider its functional importance in the inflamed joint. METHODS: Therapeutically aspirated synovial fluids (pooled and individual samples, n = 66) were obtained from patients with arthritis. In addition, serum (n = 14) was collected from RA patients, and saliva (n = 10) and urine (n = 10) from normal individuals. Enzymic (amidase) and immunoreactive activities of PK and its precursor, prokallikrein (PPK), were determined. The presence of PK was assessed by incubation with soya bean trypsin inhibitor (SBTI), and by adsorption with anti-PK antibody linked to Sepharose. An enzyme linked immunosorbant assay (ELISA) for PK was developed for quantitative measurement of total PK in biological fluids. Enhancement of the PK dose-response by RA synovial fluid made it necessary to remove RF from synovial fluids before determination of PK by ELISA. RESULTS: Amidase activity was demonstrated in synovial fluid pools and shown to be inhibited completely by SBTI, and removed by prior treatment with anti-PK Sepharose. Total PK activity (PK + PPK) from individual synovial fluid specimens did not differ significantly between patients with RA (median activity 76 mU/g protein), PA (80 mU/g protein) or OA (60 mU/g protein). Similar results were obtained when active PK alone was measured. No correlation was found between active PK or total PK values and the severity score for individual joints. Most of the measured immunoreactivity was removed by adsorption with anti-PK antibody linked to Sepharose. CONCLUSION: The results support the hypothesis that plasma kallikrein is present in synovial fluid. The enzyme may be important in the pathogenesis of inflamed joints. PMID- 7794041 TI - Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. AB - OBJECTIVES: To clarify the pathophysiological role of endothelin-1 (ET-1) in the vascular injury associated with systemic lupus erythematosus (SLE) by investigating the effect of sera from patients with SLE on ET-1 release from cultured human umbilical vein endothelial cells. METHODS: Confluent monolayers of cultured human umbilical vein endothelial cells were incubated with serum samples (diluted 1:10) from 25 patients with SLE and 16 normal controls for two hours at 37 degrees C and ET-1 concentration in the culture supernatant was measured by enzyme immunoassay. RESULTS: The mean release of ET-1 from endothelial cells in the presence of serum from SLE patients was greater than in the presence of serum from normal controls (p < 0.005). ET-1 release from endothelial cells significantly correlated with the titre of IgM anti-endothelial cell antibodies (IgM-AECA) and immune complex concentration in sera from SLE patients (p < 0.05 and p < 0.01, respectively). After gel chromatography of the serum from an SLE patient, those fractions containing IgM-AECA or immune complex were shown to stimulate ET-1 release from endothelial cells. Heat aggregated IgG also stimulated ET-1 release from endothelial cells in a concentration dependent manner. CONCLUSIONS: IgM-AECA and immune complexes may stimulate ET-1 release from endothelial cells and ET-1 may play an important role in the initiation and development of vascular injury, such as pulmonary hypertension and lupus nephritis, in SLE. PMID- 7794042 TI - Role of TNF alpha in the induction of antigen induced arthritis in the rabbit and the anti-arthritic effect of species specific TNF alpha neutralising monoclonal antibodies. AB - OBJECTIVE: To investigate the role of tumour necrosis factor alpha (TNF alpha) in the development of antigen induced arthritis (AIA) in rabbits. METHODS: Monoclonal antibodies to rabbit TNF alpha were developed in rats and were used to detect TNF alpha in synovial fluid by enzyme linked immunosorbent assay and to localise it in tissue sections of synovium and cartilage from rabbits up to 21 days after induction of AIA. An antibody which neutralised TNF alpha activity in vitro was injected into rabbits to block TNF alpha action in vivo in AIA. Joint swelling, leucocyte infiltration into synovium and proteoglycan loss from cartilage were measured and compared with a control group, which were injected with sterile saline. RESULTS: Monoclonal antibodies to purified rabbit TNF alpha were prepared in rats and two were selected which were able to neutralise rabbit TNF alpha in a cytotoxicity bioassay. TNF alpha was detected in significant concentrations (21.7 (SE 0.5) pg/ml) in the arthritic joint fluid of rabbits with AIA only at one day after induction and it was then also sparsely localised in cells of the synovium, but from day 3 onwards it was localised more strongly in the deep zone of articular cartilage. Injection of anti-TNF monoclonal antibody R6 over three days into rabbits with AIA reduced joint swelling and leucocyte infiltration into joint fluid and decreased the expression of CD11b and CD18 on cells in the joint fluid. However, there was no significant reduction in the loss of proteoglycan from articular cartilage, although the joint fluid at three days contained a lower glycosaminoglycan content. The antibody R6 gave most effect at a dose of 0.6 mg/kg and there was no increase in its effectiveness at a fivefold greater dose (3.0 mg/kg). Treatment over 10 days gave a more complete suppression of joint swelling, but did not result in any less proteoglycan loss from cartilage. Treatment for five days with a 16 day follow up gave a significant reduction in swelling for several days beyond the treatment, but the swelling then slowly returned, until by day 21 there was no significant difference in joint swelling and there was also no recovery of cartilage proteoglycan content. A rabbit anti-rat immunoglobulin response was detected at 21 days, which may have limited the long term effectiveness of the antibody. CONCLUSIONS: In AIA in rabbits, TNF alpha was only detected in synovial fluid at one day after induction and there was only limited cellular localisation of TNF alpha in synovium and cartilage from three days. However, neutralising TNF alpha with a monoclonal antibody was effective in suppressing inflammatory changes in the joint during the acute onset of AIA, but it had little effect on the loss of proteoglycan from cartilage. The results suggest that blocking inflammation and synovitis with anti TNF alpha may be more easily achieved than preventing damage to articular cartilage. PMID- 7794039 TI - Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia. AB - OBJECTIVE: To elucidate the relationship, if any, between lipid abnormalities and apolipoprotein E (apo E) polymorphism, by investigating apo E phenotype and allele frequency. METHODS: Fasting blood samples were taken for determination of apo E phenotype and serum lipids in 221 male patients with gout and 141 control male subjects. Apo E phenotype was determined by one dimensional flat gel isoelectric focusing. RESULTS: Frequencies of apo E phenotypes in gout were apo E3/3 67.9%, E4/3 18.1%, E4/4 2.3%, E4/2 1.8%, E3/2 9.5%, and E2/2 0.5%; those in control male subjects were 74.5%, 15.6%, 0%, 1.4%, 7.1%, and 1.4%, respectively. Frequencies of the e2, e3, and e4 alleles in gout were 0.061, 0.817 and 0.122, compared with the corresponding control frequencies of 0.057, 0.858 and 0.085. These differences in apo E phenotype and allele frequencies between gout and control subjects were not significant. The frequency of apo e4 allele in hyperlipidaemic gout subjects was significantly greater than that in normolipidaemic gout subjects; in contrast, its frequency was not different between hyperlipidaemic and normolipidaemic control subjects. Serum triglyceride, total cholesterol, apo B and E concentrations were significantly greater in gouty patients with the apo E4/3 phenotype than in those with gout having the apo E3/3 phenotype. CONCLUSIONS: These data suggest that gout subjects with hyperlipidaemia (hypertriglyceridaemia, hypercholesterolaemia or both) possess the apo e4 allele with higher frequency than those with normolipidaemia. They also suggest that apo e4 may induce some susceptibility to the development of hyperlipidaemia in gout in addition to that induced by obesity or excessive alcohol consumption, and may contribute to the high prevalence of atherosclerotic diseases in gout patients. PMID- 7794040 TI - Novel 68 kDa autoantigen detected by rheumatoid arthritis specific antibodies. AB - OBJECTIVE: To improve the understanding of the pathogenesis of rheumatoid arthritis (RA) by identifying novel, disease specific autoantibodies. METHODS: Total protein preparations from synovial membranes were separated electrophoretically and immunoblotted. Sera from RA patients were screened for predominant immunoreactions by blotting. A 68 kDa antigen target of the most predominant reaction was detected and further characterised. RESULTS: The dominant immunoreaction in most of the RA sera tested was with a 68 kDa antigen. The antigen is probably ubiquitously expressed. It has an isoelectric point of 5.1, is O-glycosylated, and is located in the endoplasmic reticulum, the cytoplasm, or both. Antibodies to the 68 kDa autoantigen were present in 64% of 167 RA patients tested, and could also be detected in seronegative RA patients, but were present in only 1% of 98 patients with other rheumatic diseases. They could not be detected in 55 healthy controls. CONCLUSIONS: Because of its high sensitivity (64%) and specificity (99%), the anti-68 kDa autoantibody not only provides another valuable parameter for diagnosis, but also represents an antibody that may be involved in the pathological mechanisms leading to RA. This hypothesis can be tested by investigating if 68 kDa specific T cells are present in RA patients. PMID- 7794043 TI - Vertebral hyperostosis and diabetes mellitus: a case-control study. AB - OBJECTIVE: To compare glucose metabolism in patients with vertebral hyperostosis (VH), with that in control patients. METHODS: We studied 50 patients aged 60 years or more who had VH according to Resnick's criteria, and 50 control patients without VH, matched for sex, age, weight and height. Plasma glucose was evaluated before and 120 minutes after ingestion of 75 g glucose. World Health Organisation criteria for diabetes mellitus (DM) were used. Radiographs of the pelvis and thoracic and lumbar spine were performed and read blind by two physicians. RESULTS: Statistical analysis showed no difference between cases and control patients for prevalence of DM, and plasma glucose at 0 and 120 minutes. CONCLUSION: These data suggest that glucoregulation in patients with VH does not differ from that in matched controls. PMID- 7794045 TI - Long term treatment of rheumatoid arthritis with high doses of intravenous immunoglobulins: effects on disease activity and serum cytokines. AB - OBJECTIVE: To evaluate the effects of long term treatment of rheumatoid arthritis (RA) with high doses of intravenous immunoglobulins (IVIg). METHODS: Ten patients with active RA and prior unsuccessful treatment with at least one slow acting antirheumatic drug were treated with 400 mg/kg of IVIg for the first three days and then once a month for 12 months. Clinical evaluation and laboratory analysis were performed every month. Serum levels of tumour necrosis factor alpha (TNF alpha), soluble interleukin-2 receptor (sIL-2R), IL-1 alpha, IL-1 beta, IL-6 and interferon gamma (IFN gamma) were measured at baseline and at three monthly intervals for 15 months. RESULTS: Although laboratory parameters were not influenced by the treatment, a late but significant clinical improvement was observed after six months. Serial measurement of cytokines revealed a rapid and persistent decrease in serum TNF alpha and a late and significant reduction in sIL-2R concentrations. CONCLUSION: This study suggests that IVIg can ameliorate the symptoms and improve the functional capability of RA patients. This effect is associated with a partial modulation of serum concentrations of inflammatory cytokines and, more interestingly, with a late decrease in sIL-2R which correlated with the late reduction in disease activity. PMID- 7794044 TI - Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. AB - OBJECTIVE: To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy. METHODS: Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ). RESULTS: Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response. CONCLUSIONS: THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection. PMID- 7794046 TI - TAP polymorphism in patients with Behcet's disease. AB - OBJECTIVE: To determine if susceptibility to Behcet's disease (BD) is associated with polymorphism of HLA-DRB1, HLA-DQB1, DQB1, and TAP1 and TAP2 genes. METHODS: Fifty eight Spanish BD patients and 116 ethnically matched unrelated healthy subjects were typed at the HLA-DRB1 and HLA-DQB1 loci using polymerase chain reaction/sequence specific oligotyping (PCR/SSO). TAP1 and TAP2 alleles were assigned using amplification refractory mutation system-PCR. RESULTS: TAP1C was absent in BD patients, but was found in 12.1% of control subjects (pcorr < 0.05; relative risk = 0.06). Additionally, a linkage disequilibrium between HLA DQB1*0501 and TAP2B was observed in BD patients (delta = 0.095, pcorr < 0.02), but not in the control group (delta = -0.0031, p > 0.05). CONCLUSIONS: The complete absence of TAP1C alleles in BD patients may indicate that TAP1 polymorphism is not without some significance in the development of BD. Furthermore, the existence of a linkage disequilibrium between HLA-DQB1*0501 and TAP2B in our patients suggests that the gene conferring susceptibility for BD is inherited as an extended haplotype in the population studied. PMID- 7794047 TI - Second international meeting on synovium. Cell biology, physiology and pathology. 21-23 September, Canterbury, United Kingdom. PMID- 7794048 TI - Synovial macrophages. PMID- 7794049 TI - Synovial intimal fibroblasts. PMID- 7794050 TI - Extracellular matrix of the synovial intimal cell layer. PMID- 7794051 TI - Synovial hyaluronate in rheumatoid arthritis binds C1q and is covalently bound to antibodies: a model for chronicity. PMID- 7794052 TI - Interaction between synoviocytes and extracellular matrix in vitro. PMID- 7794054 TI - Synovial perfusion and synovial fluid solutes. PMID- 7794055 TI - Functions of hyaluronan. PMID- 7794053 TI - Fluid movement across synovium in healthy joints: role of synovial fluid macromolecules. PMID- 7794056 TI - Effect of synovial fluid hyaluronan on the clearance of albumin from the canine knee. PMID- 7794057 TI - Effect of long term intramuscular gold therapy on the seroprevalence of Helicobacter pylori in patients with early rheumatoid arthritis. PMID- 7794058 TI - Vertebral fracture induced by chronic contained rupture of aortic aneurysm. PMID- 7794059 TI - [Eugene Jamot and Emile Lejeune. Historical pages]. PMID- 7794060 TI - Malaria vector control: a critical review on chemical methods and insecticides. PMID- 7794061 TI - [Plasmodium falciparum index and level of parasitemia: diagnostic and prognostic value in the Congo]. AB - Parasitological data of various malarial studies performed in the Congo where Plasmodium falciparum malaria is holo-endemic in rural and suburban zones, between 1988 and 1991, were analyzed with the intention of establishing diagnosis and prognosis value of Plasmodium falciparum parasitaemia in areas with high perennial transmission. In such an area congolese school-children (6-10 years old) had 88% P. falciparum index, this is the same percentage as that for children hospitalized with a pernicious attack. However, the parasite load is distributed differently; parasitaemia is greater than 6,000 asexual form of P. falciparum/microliters (afPf/microL) in only 4.6% of cases in the former group versus 67% in the second group. A threshold of 10,000 afPf/microliters, above which the Plasmodium infection triggers a febrile attack in semi-immune children, is confirmed in school children in a rural context where the factor of taking antimalarial drugs within the preceding days is negligible; three out of four children with levels above this threshold are febrile versus 4.1% (7 out of 170) with lower blood parasite levels. Some adults were also asymptomatic carriers but much less frequently and with lower mean parasitaemia levels. The parasite load mirrors the clinical severity although this concept can be misleading as an individual prognostic criterion and for hospital studies carried out in areas where multiple drug administration before hospitalisation is common. For the studies recently performed in Brazzaville, the 5% threshold level of parasitized red cells, the WHO severity criterion, was never reached in asymptomatic subject or in cases of simple attack; it was reached in one out of two cases of pernicious attack. PMID- 7794062 TI - Malaria vectors and transmission in an area deforested for a new international airport in southern Cameroon. AB - Nsimalen, a village in Southern Cameroon, has been deforested over a surface of 370 hectares for the construction of the new Yaounde international airport (Cameroon). Mosquitoes night catches on human bait were performed over a year in two hamlets of this village, one adjoining the airport and the other situated 3 kilometers off the deforested area. The aim of the survey was to observe malaria vectors and transmission around the airport and to record malaria epidemiological changes resulting from deforestation. The findings showed that the main malaria vector was Anopheles moucheti (95% of the vector population). Anopheles gambiae was also present but in very small quantities. The increased density of the latter near the airport combined with the low parity rates, indicated that deforestation favoured the breeding of this species. Malaria transmission was estimated at 106 and 68 infective bites per man per year in hamlets close to and far away from the airport zone respectively. An. gambiae accounted for 13% of the transmission in the hamlet adjoining the airport and 0% three kilometers off the airport. PMID- 7794063 TI - An etiologic study of hemoglobinuria and blackwater fever in the Kivu Mountains, Zaire. AB - Between January 1985 and March 1986, in the high altitude area of Kivu, Eastern Zaire, 38 patients presenting with hemoglobinuria as main manifestation were investigated. Profound glucose-6-phosphate dehydrogenase deficiency was detected in 4 patients, leptospirosis in 2 and Hantaan virus infection in 2. Hemolysis was doubtful (haptoglobin > 40 mg/dl, Hemoglobin > 12 g/dl) in 2 patients. Other potential causes of hemoglobinuria such as hemoglobinopathy, toxic agents, infectious diseases or blood transfusion incompatibility were carefully screened and excluded. The syndrome observed in the remaining 28 cases was strongly suggestive of blackwater fever (BWF) as described in malaria patients by several authors under the french name "fievre bilieuse hemoglobinurique". Quinine was used as curative treatment of malaria before admission in a significant greater proportion (p < 0.01) of patients with BWF compared to patients with uncomplicated malaria, suggesting that this drug might have played a triggering role in the genesis of BWF. However, quinine was usually administered at inadequate doses to malaria patients non responding to chloroquine and belonging to a population of whom 50% are non immune. It may thus also be hypothesized that BWF in our patients could result from a hyperparasitemic state that remained undetected because of an unusual synchronous lysis of infected erythrocytes. In the latter case BWF would correspond to a major complication of falciparum malaria only coincidentally related to the use of quinine. PMID- 7794064 TI - Alternative application of melarsoprol for treatment of T. B. gambiense sleeping sickness. Preliminary results. AB - The protocols for treatment of human African trypanosomiasis (sleeping sickness) with the organoarsenical drug melarsoprol are based on empirical observations. Therapy is often accompanied by serious side effects and relapses. Additionally, the duration of treatment, which is up to forty days, is a major drawback in African countries. Based on pharmacokinetic investigations an alternative therapy protocol for T. gambiense sleeping sickness has recently been proposed which consists of ten consecutive injections of 2.2 mg/kg melarsoprol given at intervals of 24 hours. In a preliminary study, eleven patients were treated in Vanga, Zaire following this alternative protocol which reduces the duration of the treatment to ten days. The results indicate that the alternative schedule was as effective as the traditional protocol, showed similar adverse reactions but required a much shorter treatment period. PMID- 7794065 TI - Combined chloroquine and primaquine resistant Plasmodium vivax malaria in a patient returning from India. PMID- 7794066 TI - Results of pancreas transplantation with portal venous and enteric drainage. AB - PURPOSE: The standard method for pancreatic transplantation involves drainage of exocrine secretions into the urinary bladder with venous outflow into the systemic circulation. Despite the high success rate associated with this approach, it often leads to complications, including chemical cystitis, reflux pancreatitis, metabolic acidosis, and hyperinsulinemia. The authors developed a new technique of pancreatic transplantation with portal drainage of endocrine secretions and enteric drainage of exocrine secretions (PE), which theoretically should be more physiologic. PROCEDURES: All patients were insulin-dependent diabetics with end-stage renal disease who underwent combined kidney-pancreas transplantation. Between 1990 and 1994, 19 patients have been transplanted using intraperitoneal placement of the pancreas allograft with exocrine drainage into a Roux-en Y loop and venous drainage into the portal circulations (PE). A comparison group of all patients undergoing standard systemic-bladder (SB) transplantation between April 1989 and March 1993 (n = 28) also was studied. Patient follow-up ranges from 6 months to 5 years for the SB patients (mean = 2.5 years) and 6 months to 4 years for the PE patients (mean = 1.6 years). Routine follow-up includes documentation of the clinical course and detailed endocrine studies. FINDINGS: Patient and graft actuarial survival at 1 and 3 years is no different for SB and PE patients. Urinary tract infections occurred in 89.3% of the SB patients (2.8/patient) versus 26.3% of the PE patients (0.25/patient, p < or = 0.0001). None of the PE patients experienced hematuria compared with 53.6% of the SB patients (p < or = 0.0001); however, two PE patients had melanotic episodes. The incidence of urinary retention and reflux pancreatitis was 32.1% versus 5.3% (p < or = 0.028) for SB and PE groups, respectively. Patients in the SB group required sodium bicarbonate therapy (mean = 55 mEq/day) although no PE patient required routine therapy; despite this, SB patients experienced more episodes of acidosis (44 vs. 5). Endocrine studies indicate no difference in glycosylated hemoglobin or fasting and stimulated glucose values throughout the follow-up period. In contrast, hyperinsulinemia was evident in both fasting and stimulated tests for the SB patients, with values consistently two- to fivefold higher than those of the PE group. CONCLUSIONS: These results indicate that PE and SB pancreas transplantation are equivalent in terms of patient and graft survival and suggest that the PE approach is associated with a decreased incidence of metabolic and bladder-related complications. In addition, the PE approach eliminates the state of peripheral hyperinsulinemia that characterizes the SB procedure. Continued follow-up will be necessary to determine if long-term outcomes will differ for patients with PE and SB grafts. PMID- 7794067 TI - Decreased mortality of severe acute pancreatitis after proximal cytokine blockade. AB - OBJECTIVE: This study determined the ability of interleukin-1 receptor antagonist (IL-1ra) to decrease the mortality of experimental acute pancreatitis. The response of the inflammatory cytokine cascade and its subsequent effects on pancreatic morphology were measured to determine the role of these peptides in mediating pancreatic injury. SUMMARY BACKGROUND DATA: Previous studies have shown that proinflammatory cytokines are produced in large amounts during acute pancreatitis and that blockade at the level of the IL-1 receptor significantly decreases intrinsic pancreatic damage. The subsequent effect on survival is not known. METHODS: A lethal form of acute hemorrhagic necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented (CDE) diet for 72 hours. For determination of mortality, the animals were divided into 3 groups of 45 animals each: control subjects received 100/microL normal saline intraperitoneally every 6 hours for 5 days; IL-1ra early mice received recombinant interleukin-1 receptor antagonist 15 mg/kg intraperitoneally every 6 hours for 5 days beginning at time 0; IL-1ra late mice received IL-1ra 15 mg/kg intraperitoneally every 6 hours for 3.5 days beginning 1.5 days after introduction of the CDE diet. A parallel experiment was conducted simultaneously with a minimum of 29 animals per group, which were sacrificed daily for comparisons of serum amylase, lipase, IL-1, IL-6, tumor necrosis factor alpha, IL-1ra, pancreatic wet weight, and blind histopathologic grading. RESULTS: The 10-day mortality in the untreated control group was 73%. Early and late IL 1ra administration resulted in decreases of mortality to 44% and 51%, respectively (both p < 0.001). Interleukin-1 antagonism also was associated with a significant attenuation in the rise in pancreatic wet weight and serum amylase and lipase in both early and late IL-1ra groups (all p < 0.05). All control animals developed a rapid elevation of the inflammatory cytokines, with maximal levels reached on day 3. The IL-1ra-treated animals, however, demonstrated a blunted rise of these mediators (all p < 0.05). Blind histologic grading revealed an overall decrease in the severity of pancreatitis in those animals receiving the antagonist. CONCLUSIONS: Early or late blockade of the cytokine cascade at the level of the IL-1 receptor significantly decreases the mortality of severe acute pancreatitis. The mechanism by which this is accomplished appears to include attenuation of systemic inflammatory cytokines and decreased pancreatic destruction. PMID- 7794068 TI - Optimal management of the pancreatic remnant after pancreaticoduodenectomy. AB - OBJECTIVE: The authors evaluated methods of operative management of the pancreatic remnant after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Despite reductions in mortality after pancreaticoduodenectomy, leakage from the pancreatic remnant still may cause significant morbidity. Patients with small, unobstructed pancreatic ducts or soft, friable pancreata are at particularly high risk. Although numerous surgical techniques have been described to avoid such complications, no single method is suitable for all patients. METHODS: The authors retrospectively reviewed the medical records of 114 consecutive patients who underwent pancreaticoduodenectomy. Sixty-nine patients were men (61%) and 45 were women (39%), with median age 66 years. Underlying disease was malignant in 87 (76%) and benign in 27 (24%). Patients were divided into groups based on risk for postoperative pancreatic fistula and on the operative management of the pancreatic remnant. Sixty-eight patients underwent end-to-side pancreaticojejunostomy, 13 of whom were high risk (group 1A) and 55 of whom were low risk (group 1B). Thirty-seven patients, all high risk, had either pancreatic duct closure by oversewing (N = 19, group 2) or end-to-end pancreaticojejunal invagination (N = 18, group 3). Nine patients underwent total pancreatectomy (group 4). Morbidity related to prolonged pancreatic drainage (PPD) of greater than 20 days was determined. RESULTS: Overall incidence of PPD was 17% and caused the only death. Patients considered high risk for postoperative pancreatic fistula had a 36% incidence of PPD compared with 2% in patients considered low risk (p < 0.0001). Prolonged pancreatic drainage frequency related to the method of pancreatic remnant management was as follows: group 1A, 15%; group 1B, 2%; group 2, 79%; and group 3, 6% (p < 0.001 for group 2 vs. other groups). No serious sequelae followed PPD in 15 patients (79%); however, 4 patients required reoperation for pseudocyst or abscess drainage; one in group 1A (who died) and three in group 2. Multivariate analysis revealed that operative technique (oversewing of the pancreatic duct) and male sex were significant factors predisposing a patient to the development of PPD. CONCLUSION: After pancreaticoduodenectomy, pancreatic remnant management by end-to-side pancreaticojejunostomy appeared safe in low-risk patients. In high-risk patients, end-to-end pancreaticojejunal invagination was the safest option. Morbidity was greatest after pancreatic duct closure without anastomosis. PMID- 7794070 TI - Treatment of hyperesthetic neuropathic pain in diabetics. Decompression of the tarsal tunnel. AB - OBJECTIVE: The authors evaluated the causal relationship between entrapment of the posterior tibial nerve and neuropathic pain and describe the results of nerve decompression in a selected group of patients with intractable pain. SUMMARY BACKGROUND DATA: Painful metabolic neuropathy has, until recently, been thought to be an irreversible and essentially untreatable complication of diabetes. Recent studies have shown that metabolic deterioration is only one component of the disease process. METHODS: A group of patients with intractable painful neuropathy and a positive percussion sign underwent posterior tibial nerve decompression. RESULTS: Nerve decompression relieved the pain in the majority of treated patients. Return of other sensory function also was noted. CONCLUSIONS: Painful diabetic neuropathy of the lower extremities is potentially reversible. It appears to be caused partially by nerve entrapment and can be reversed by decompression. PMID- 7794069 TI - Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns. AB - BACKGROUND: Human growth hormone is an anabolic agent that attenuates injury induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering > 40% of total body surface area. OBJECTIVE: The authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. METHODS: Ten massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. RESULTS: Donor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. CONCLUSION: Results indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural proteins and other components needed to rebuild the junctional structures. PMID- 7794071 TI - Mechanisms of transplant right ventricular dysfunction. AB - OBJECTIVE: Right ventricular (RV) dysfunction remains the leading cause of early mortality after cardiac transplantation. The effect of brain death and subsequent hypothermic cardioplegic arrest and storage on subsequent post-transplant right ventricular function was examined. SUMMARY BACKGROUND DATA: Right ventricular dysfunction in the donor heart usually is attributed to failure of the donor right ventricle to adapt to the sudden increase in afterload (pulmonary vascular resistance) in the recipient. Strategies to improve ventricular mechanics in the postoperative period are aimed at reducing pulmonary vascular resistance with vasodilators or augmenting right ventricular contractility with inotropic agents. Events occurring in the donor heart (brain death, hypothermic cardioplegic arrest, and storage) also may be directly related to post-transplant RV dysfunction. METHODS: A canine model of brain death and orthotopic cardiac transplantation was used. A dynamic pressure-volume analysis of RV mechanics was performed using micromanometers and sonomicrometric dimension transducers. Systolic function was assessed by measurement of preload recruitable stroke work (PRSW). Brain death was induced in 17 dogs by inflation of an intracranial balloon. Right ventricular function then was assessed serially to 6 hours (PRSW). Right ventricular adrenergic beta receptor density and function was sampled at control and after 6 hours of brain death. The effect of cardioplegic arrest and hypothermic storage was assessed in a second group of 17 dogs, using the same instrumentation and method of RV analysis. RESULTS: A significant decrease in right ventricular PRSW occurred after brain death, with the average decrease being 37% +/- 10.4% from the control. The RV myocardial beta adrenergic receptor density did not significantly change (253 +/- 34 fmol/ng control vs. 336 +/- 54 fmol/ng after brain death). The adenylyl cyclase activity of the RV beta receptor was assessed and was not altered by brain death. Orthotopic transplantation after cardioplegic arrest and hypothermic storage significantly decreased RV PRSW from 23.6 +/- 2.0 x 10(3) erg to 13.5 +/- 1.4 x 10(3) erg. CONCLUSIONS: These data indicate that the donor right ventricle is exposed to factors significantly detrimental to its mechanical performance well before facing an increased afterload in the recipient. Strategies to reduce RV dysfunction associated with brain death and hypothermic storage could positively impact post-transplant survival. PMID- 7794072 TI - The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus. AB - OBJECTIVE: Studies in breast cancer suggest that p53 and c-erb B2 protein overexpression are predictive of outcome. The authors determined whether these molecular markers correlated with treatment response and survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. METHOD: Immunostaining for p53 and c-erb B2 was performed on paraffin-embedded specimens from 42 patients with esophageal adenocarcinoma. All patients received neoadjuvant chemotherapy (cisplatin and fluorouracil [5-FU] x 3 cycles) and irradiation (4500 rads) followed by resection. RESULTS: In this cohort of patients, 79% (33/42) were positive for p53, and 43% (18/42) were positive for c erb B2. p53 positivity correlated with residual disease in the resection specimen but not with disease-free survival. Although c-erb B2 negatively correlated with residual disease after resection and a 5-year survival of 10%, c-erb B2 positivity was associated with a 5-year actuarial survival of 60%. CONCLUSIONS: Although p53 protein overexpression is commonly observed in adenocarcinoma of the esophagus, its prognostic value appears limited. In contrast, c-erb B2 protein expression predicts a favorable response to therapy and improved survival. PMID- 7794073 TI - Downstaging of esophageal cancer after preoperative radiation and chemotherapy. AB - OBJECTIVE: This retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. METHODS: Forty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent "potentially curative" resections-transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. RESULTS: There were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1- and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5 year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). CONCLUSION: Although retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics. PMID- 7794074 TI - Noninvasive diagnosis of mesenteric ischemia using a SQUID magnetometer. AB - OBJECTIVE: The authors assessed the ability of a Superconducting Quantum Interference Device (SQUID) magnetometer to noninvasively detect mesenteric ischemia in a rabbit model. SUMMARY BACKGROUND DATA: Superconducting Quantum Interference Device magnetometers have been used to detect magnetic fields created by the basic electrical rhythm (BER) and to detect changes in BER of exteriorized bowel of anesthetized rabbits during mesenteric ischemia. METHODS: The BER of rabbit ileum was noninvasively measured transabdominally using a SQUID magnetometer and compared with the electrical activity recorded with surgically implanted serosal electrodes before, during, and after snare occlusion of the superior mesenteric artery. RESULTS: Transabdominal SQUID recording of BER frequency was highly correlated to the measurements obtained with electrodes (R = 0.91). Basic electrical rhythm frequency decreased from 16.4 +/- 0.8 to 8.3 +/- 0.3 cpm (p < 0.001) after 25 minutes of ischemia. Reperfusion of ischemic bowel resulted in recovery of BER frequency to 14.3 +/- 0.4 cpm 10 minutes after blood flow was restored. CONCLUSIONS: A SQUID magnetometer is capable of noninvasively detecting mesenteric ischemia reliably and at an early stage by detecting a significant drop in BER frequency. These positive findings have encouraged the authors to continue development of clinically useful, noninvasive, detection of intestinal magnetic fields using SQUID magnetometers. PMID- 7794075 TI - Oncogene protein co-expression. Value of Ha-ras, c-myc, c-fos, and p53 as prognostic discriminants for breast carcinoma. AB - OBJECTIVE: A refinement of prognostic variables using traditional pathologic markers integrated with oncogene proteins, enzymes, and hormonal factors may enhance the ability to predict for recurrence or survival in patients with mammary carcinoma. Although various oncogenes and oncogene products have been identified in human breast carcinoma, their relationship to disease outcome remains controversial. METHODS: Using the monoclonal antibodies cS93.1, 9E1.0, F235-1.7.1, and PAb 1801 against each oncogene protein studied, the avidin-biotin complex immunoperoxidase method provided immunohistochemical staining of bound oncogene protein for c-fos, c-myc, Ha-ras, and p53, respectively. Analyses were made on archival pathology tissues of 85 breast cancer patients (stages I, IIA, and IIB). Forty patients (47%) had recurrence of disease; 45 remained free of local-regional or distant disease at mean follow-up of 48 months (range 6-180 months). Molecular biological data were merged with clinicopathologic demographics 1) to determine the frequency of single or co-expression of oncogenes in this patient population; 2) to evaluate the value of these molecular protein markers to predict probability of recurrence; and 3) to determine worth of the studied oncogenes to correlate with traditional clinical pathologic parameters and overall survival. RESULTS: In this study, oncogene expression had statistical correlation for recurrence with increasing co-expression: one oncogene 17.2%, two oncogenes 56.3%, three or four oncogenes, 100% (p = 0.001). Increasing oncogene or co-oncogene expression correlated with statistically significant reduction in disease-free and overall survival; with no expression of oncogenes, disease-free survival was 30 (SE +/- 5.7) months and overall survival was 56.4 (SE +/- 4.57) months. With expression of three oncogenes, disease-free survival was 12 (SE +/- 1.23) months (p = 0.0018) and overall survival was 23.4 (SE +/- 3.38) months (p = 0.0025). In univariate Wilcoxon analysis, oncogene expression was the most significant variable to determine survival (p = 0.035); in multivariate analysis, age and oncogene co-expression each emerged as the most significant variables for overall survival. For the proportional hazards regression model, oncogene co-expression was significant (p = 0.0104, risk-ratio 1.914) and correlated with age and tumor size as significant variables. Ha-ras and c-fos both emerged as important individual oncogene proteins to affect survival (p = 0.0925, risk-ratio 3.517 and p = 0.025, risk-ratio 4.214, respectively). The proto-oncogene c-myc and the antitumor suppressor gene p53 did not have significant effects as individual oncogenes to influence survival. CONCLUSIONS: Approximately one fifth of the breast cancer patients in this analysis (disease-free and recurrent) expressed only a single oncogene marker (c fos, c-myc, Ha-ras, or p53); one quarter of patients with recurrent disease expressed only one oncogene protein. Single oncogene expression did not possess independent prognostic significance for prediction of recurrence. Further, p53 mutations did not function as independent correlates for prognosis. The co expression of the studied proto-oncogenes (c-myc, Ha-ras) and the nuclear transcriptional protein (c-fos) functioned as a strong prognostic correlate for recurrence and survival; the effect of individual oncogenes to predict survival was greatest for Ha-ras and c-fos. Immediate or early co-expression of three oncogene proteins in neoplastic transformation endowed cells of invasive carcinoma with an aggressive phenotype. This aggressive phenotype was evident in a small percentage of the studied population (11%) and predicted adverse disease free and overall survival. These findings suggest that oncogene co-expression possesses significant prognostic and potential therapeutic value; incorporation of this molecular technology into future prospective randomized trials is advisable. PMID- 7794077 TI - Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma. AB - OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease. PMID- 7794076 TI - Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. AB - OBJECTIVE: This single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. METHODS: Two hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. RESULTS: The overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections; n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, < 800 mL intraoperative blood loss, < 2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection. CONCLUSIONS: The survival of patients with pancreatic adenocarcinoma treated by pancreaticoduodenectomy is improving. Aspects of tumor biology, such as DNA content, tumor diameter, nodal status and margin status, are the strongest predictors of outcome. PMID- 7794078 TI - Nonoperative management of blunt hepatic trauma is the treatment of choice for hemodynamically stable patients. Results of a prospective trial. AB - BACKGROUND: A number of retrospective studies recently have been published concerning nonoperative management of minor liver injuries, with cumulative success rates greater than 95%. However, no prospective analysis that involves a large number of higher grade injuries has been reported. The current study was conducted to evaluate the safety of nonoperative management of blunt hepatic trauma in hemodynamically stable patients regardless of injury severity. METHODS: Over a 22-month period, patients with blunt hepatic injury were evaluated prospectively. Unstable patients underwent laparotomies, and stable patients had abdominal computed tomography (CT) scans. Those with nonhepatic operative indications underwent exploration, and the remainder were managed nonoperatively in the trauma intensive care unit. This group was compared with a hemodynamically matched operated cohort of blunt hepatic trauma patients (control subjects) who had been prospectively analyzed. RESULTS: One hundred thirty-six patients had blunt hepatic trauma. Twenty-four (18%) underwent emergent exploration. Of the remaining 112 patients, 12 (11%) failed observation and underwent celiotomy--5 were liver-related failures (5%) and 7 were nonliver related (6%). Liver related failure rates for CT grades I through V were 20%, 3%, 3%, 0%, and 12%, respectively, and rates according to hemoperitoneum were 2% for minimal, 6% for moderate, and 7% for large. The remaining 100 patients were successfully treated without operation--30% had minor injuries (grades I-II) and 70% had major (grades III-V) injuries. There were no differences in admission characteristics between nonoperative success or failures, except admission systolic blood pressure (127 vs. 104; p < 0.04). Comparing the nonoperative group to the control group, there were no differences in admission hemodynamics or hospital length of stay, but nonoperative patients had significantly fewer blood transfusions (1.9 vs. 4.0 units; p < 0.02) and fewer abdominal complications (3% vs. 11%; p < 0.04). CONCLUSIONS: Nonoperative management is safe for hemodynamically stable patients with blunt hepatic injury, regardless of injury severity. There are fewer abdominal complications and less transfusions when compared with a matched cohort of operated patients. Based on admission characteristics or CT scan, it is not possible to predict failures; therefore, intensive care unit monitoring is necessary. PMID- 7794080 TI - Colon cancer cells that are not growth inhibited by TGF-beta lack functional type I and type II TGF-beta receptors. AB - OBJECTIVE: The authors determined the molecular mechanisms for the failure of transforming growth factor-beta (TGF-beta) to inhibit the growth of SW1116 and SW48 colon cancer cell lines. BACKGROUND: Transforming growth factor-beta is a bifunctional regulator of cell growth that typically stimulates proliferation of mesenchymal cells, but inhibits proliferation of normal epithelial cells. In the colon, TGF-beta appears to arrest proliferation of enterocytes as they leave the intestinal crypt and move to the villus tip. Transforming growth factor-beta actions are mediated by binding to heteromeric complexes of type I and type II TGF-beta receptors. Loss of TGF-beta responsiveness may contribute to uncontrolled cell growth and cancer. METHODS: The effects of TGF-beta 1 on DNA synthesis were measured by incorporation of tritiated thymidine into DNA of cultures of moderately differentiated adenocarcinoma (SW48) and poorly differentiated adenocarcinoma (SW1116) colon cell lines and a mink lung epithelial cell line (CCL-64). The effects of TGF-beta on the expression of c myc, TGF-alpha, and TGF-beta in SW48 cells, SW1116 cells, and CCL-64 cells (c-myc only) were measured by Northern blot analysis. Expression of TGF-beta receptors in the cell lines was measured using competitive binding assays, receptor affinity labelling techniques, and reverse transcriptase-polymerase chain reaction. RESULTS: Incubation with TGF-beta 1 (50 ng/mL) did not decrease serum stimulated uptake of [3H]-thymidine into actively growing cultures of SW48 or SW1116 cells, but suppressed DNA synthesis of actively growing CCL-64 cells by 90%. Similarly, incubation with TGF-beta 1 (12 ng/mL) for 4 hours did not substantially alter the mRNA levels of c-myc, TGF-alpha, and TGF-beta 1 in either colon tumor cell line, although levels of c-myc mRNA in CCL-64 cells were reduced by TGF-beta 1 treatment. Competitive displacement of [125I]-TGF-beta 1 binding detected high levels (16,500 TGF-beta receptors per cell) of specific, high affinity (200 pmol/L half-displacement) TGF-beta receptors on CCL-64 cells. In marked contrast, very low levels of TGF-beta 1 binding to SW1116 cells (250 receptors per cell) and SW48 cells (260 receptors per cell) were detected. Autoradiograms of CCL-64 cells affinity labelled with [125I]TGF-beta 1 revealed the presence of type I, type II, and type III TGF-beta receptors. No TGF-beta receptors were identified on SW1116 cells, and only very low levels of the nonsignaling type III TGF-beta receptors were detected on SW48 cells. Reverse transcriptase-polymerase chain reaction amplification detected mRNAs for type I, type II, and type III TGF-beta receptors in CCL-64 cells. SW48 cells, and SW1116 cells. CONCLUSIONS: These results suggest that the lack of growth inhibition by TGF-beta in SW48 and SW1116 colon cancer cells may be caused by a lack of expression of functional TGF-beta receptors. PMID- 7794079 TI - TRAM flap breast reconstruction after radiation treatment. AB - OBJECTIVE: Patients with and without radiation treatment before their breast reconstruction were compared to study the relationship of radiation to flap related complications. SUMMARY BACKGROUND DATA: The transverse rectus abdominis muscle (TRAM) flap for breast reconstruction involves a a vascular pedicle and recipient bed, both included in the radiated field of patients undergoing adjunctive therapy. Detailed reviews of flap-related complications in this subgroup of patients have been limited. METHODS: One hundred eight patients with radiation treatment who subsequently underwent a TRAM flap breast reconstruction were compared with 572 patients with no radiation treatment before similar reconstruction. Flap-related complications, radiation dosage, time, fields, relationships between risk factors, and complications were studied. RESULTS: Overall complication rates were comparable between the two groups. Only fat necrosis (> 10% of total reconstruction) was found to be statistically significant (17.6% vs. 10.1%, p = 0.03228). No difference was found for fat necrosis in unipedicled vs. bipedicled flaps controlled for radiation (17.7% vs. 17.4%). Obesity and radiation therapy were associated with fat necrosis and major infection in a logistic regression. Significant abdominal scarring was also associated with major infection (p = 0.0044). CONCLUSIONS: In this, the largest reported series, radiation therapy was associated with increased fat necrosis and major infection. The use of the TRAM flap was not found to be prohibitive in radiated patients and should still be the first choice in this subgroup of patients. PMID- 7794081 TI - Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. AB - OBJECTIVE: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. SUMMARY BACKGROUND DATA: The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. METHODS: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. RESULTS: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients. CONCLUSIONS: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency. PMID- 7794082 TI - Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. AB - OBJECTIVE: The aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma. BACKGROUND: Retrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma. However, in these reports, patients receiving radiotherapy tended to have smaller, often resectable tumors, and were relatively fit. In comparison, patients who have not received radiotherapy often had unresectable tumors, metastatic disease, or poor performance status. METHODS: From 1988 through 1993, surgically staged patients with perihilar cholangiocarcinoma and 1) no evidence of metastatic disease, 2) Karnofsky score > 60, 3) no prior malignancy or radiotherapy, and 4) a patent main portal vein were analyzed. Fifty patients were stratified by resection (n = 31) versus operative palliation (n = 19) and by radiation (n = 23) versus no radiotherapy (n = 27). RESULTS: Patients undergoing resection had smaller tumors (1.9 +/- 2.8 vs. 2.4 +/- 2.1 cm, p < 0.01) that were less likely to invade the hepatic artery (3% vs. 42%, p < 0.05) or portal vein (6% vs. 53%, p < 0.05). Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy. Resection improved the length (24.2 +/- 2.5 vs. 11.3 +/- 1.0 months, p < 0.05) and quality of survival. Radiation had no effect on the length (18.4 +/- 2.9 vs. 20.1 +/- 2.4 months) or quality of survival or on late toxicity. CONCLUSIONS: This analysis suggests that in patients with localized perihilar cholangiocarcinoma, resection prolongs survival whereas radiation has no effect on either survival or late toxicity. Thus, new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients. PMID- 7794083 TI - Prevention of embolic events after cardioversion of atrial fibrillation. Current and evolving strategies. AB - We review the incidence of embolic events following cardioversion of atrial fibrillation, as well as the literature that forms the basis for the current strategy of anticoagulation before, and following, cardioversion to reduce the risk of post-cardioversion embolism. We evaluate a new strategy that uses transesophageal echocardiography to identify patients in atrial fibrillation without atrial thrombi who may be safely cardioverted without preceding anticoagulation and we also address the embolic event and anticoagulation issues in patients with atrial flutter. Cardioversion of atrial fibrillation to sinus rhythm is associated with a small but significant risk of thromboembolic events (average incidence, 1.5%; range, 0% to 7%). Anticoagulating these patients before cardioversion appears to significantly reduce this risk, and because of the delay in return of atrial contraction, anticoagulation should be continued for several weeks following cardioversion. The current guidelines for anticoagulating patients in atrial fibrillation who are to be cardioverted is based primarily on clinical observations, numerous uncontrolled case series, two retrospective trials, and one prospective nonrandomized controlled trial. Anticoagulation for 3 weeks before cardioversion followed by 4 weeks of anticoagulation after cardioversion is a theoretically sound and effective approach to reduce the risk of thromboembolic events. The use of transesophageal echocardiography to rule out thrombus and thus identify low-risk patients who may undergo cardioversion without preceding anticoagulation has been supported by several small studies that successfully used this strategy. However, the demonstration of a postcardioversion atrial and atrial appendage "stunning" suggests that anticoagulation needs to be given at the time of, and following, cardioversion. While promising, this transesophageal echocardiography--guided strategy for cardioversion of patients in atrial fibrillation requires more rigorous study before its routine use can be recommended. The current management of pure atrial flutter requires no anticoagulation before cardioversion; however, several clinical observation suggest theoretical risks for embolic events in these patients, thus further investigation of this strategy may be warranted. PMID- 7794084 TI - The angiotensin II type 1 receptor antagonists. A new class of antihypertensive drugs. AB - The angiotensin II (AII) type 1 receptor antagonists represent a new pharmacologic class of drugs that are specifically designed to displace AII from its type 1 receptor subtype. These drugs antagonize AII-induced biologic actions, including smooth-muscle contraction, sympathetic pressor mechanisms, and aldosterone release. Initial clinical trials suggest that these drugs are effective in the treatment of essential hypertension and hypertensive patients with intrinsic renal disease. Thus, they are the newest addition to the therapeutic armamentarium for the treatment of hypertensive diseases. We review the developmental history and pharmacology of the AII type 1 receptor antagonists. We specifically discuss the following factors: mechanism(s) of action; members under clinical investigation; effects on renal function, salt and water excretion, and plasma renin activity, plasma AII type 1, and plasma aldosterone concentrations; and efficacy and safety. Given the demonstrable benefits of AII type 1 receptor blockade, these drugs should achieve broad utility in the treatment of hypertensive diseases. PMID- 7794085 TI - Peptic ulcer and gastrointestinal hemorrhage associated with nonsteroidal anti inflammatory drug use in patients younger than 65 years. A large health maintenance organization cohort study. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an elevated risk of peptic ulcer and upper gastrointestinal hemorrhage, but published reports have lacked information on rates of outpatient disease, have concentrated on the elderly, and have not provided comparisons of rates for specific types of NSAIDs. METHODS: We compared incidence rates of peptic ulcer and upper gastrointestinal hemorrhage in 68 028 people younger than 65 years who used diclofenac sodium, naproxen, piroxicam, or sulindac, and who were members of a network of health maintenance organizations. We reviewed automated insurance claims data and medical records to ascertain cases and included conditions treated on an outpatient basis. RESULTS: Medical claims data were adequate for crude identification of potential cases, but review of medical records led to rejection of 63% of these, representing either no abnormality or diseases other than peptic ulcer or upper gastrointestinal hemorrhage. Of the total 112 cases, 64 (57%) were treated as outpatients. The crude incidence rate per 1000 person years in users of any current, recent, or past NSAID was 2.2 and in distant-past users of NSAIDs was 0.75. For diclofenac, naproxen, piroxicam, and sulindac, we found a consistent pattern of decreasing NSAID effects from current to recent to past exposure. The risk of peptic ulcer or upper gastrointestinal hemorrhage was 1.6 cases per 1000 people using NSAIDs. CONCLUSIONS: Combining use of automated claims records with review of medical records promotes efficiency while maintaining specificity of case ascertainment. This study, with 57% of cases treated as outpatients, had results consistent with other published reports that were based on hospitalized patients. Within the limits of statistical error, the incidence rates of peptic ulcer and upper gastrointestinal hemorrhage appeared to be similar for the various NSAIDs studied. PMID- 7794086 TI - Low complication rate of corticosteroid-treated asthmatics undergoing surgical procedures. AB - OBJECTIVE: To determine the incidence of perioperative complications in asthmatic patients who received preoperative treatment with corticosteroids and whether these could be predicted using any study variables such as age, sex, severity of asthma, or surgery type. METHODS: Using a retrospective cohort design, we studied 71 asthmatic patients who underwent 89 surgical procedures; 86 of 89 patients received preoperative treatment with systemic corticosteroids. The main outcome measures evaluated were incidence of postoperative bronchospasm, infection, clinical evidence of adrenocortical insufficiency, and death. RESULTS: Three patients (4.5%) developed mild postoperative bronchospasm; five (5.6%) developed postoperative infections, two of which were wound infections (2.2%); there were no patients with evidence of adrenocortical insufficiency; there was one death related to a neurosurgical intraoperative complication. Incidence of infection was not statistically different from two comparison surgical groups. None of the complications was predicted using any of the study variables. CONCLUSION: Asthmatic patients who are treated preoperatively with corticosteroids can undergo surgical procedures with a low incidence of complications. PMID- 7794087 TI - Does aspirin consumption affect the presentation or severity of acute myocardial infarction? AB - BACKGROUND: While consumption of aspirin has been shown to decrease the occurrence of nonfatal cardiac events, the majority of studies have not demonstrated any impact of aspirin intake on cardiovascular mortality. The present population-based study explores the possibility that aspirin consumption affects the presentation and severity of acute myocardial infarction (AMI), and hence the likelihood of clinical detection. METHODS: We monitored the use of aspirin before admission for 2114 patients with a validated diagnosis of AMI in 16 hospitals in the Worcester, Mass, metropolitan area during 1986, 1988, and 1990. The AMIs were characterized as Q wave vs non-Q wave and large (peak creatine kinase levels more than five times normal) vs small (peak creatine kinase levels less than two times normal). RESULTS: A total of 332 patients (16%) with validated AMI took aspirin before hospital admission. Nearly 65% of aspirin users had non-Q wave AMIs, compared with 49% of nonaspirin users. Thirty percent of aspirin users sustained small AMIs, compared with 22% of nonaspirin users. These findings persisted after stratifying for previous AMI, history of coronary disease, receipt of thrombolytic therapy, and exclusion of early hospital deaths. Using multivariable regression models to control for age, gender, previous evidence of coronary disease, and use of other medications, prior aspirin consumption remained independently associated with AMI type (non-Q-wave AMI) and smaller infarct size. CONCLUSION: Aspirin consumption appears to modify the presentation of AMI, increasing the likelihood that the infarct will be of the small, non-Q-wave variety. PMID- 7794088 TI - Persistence and new onset of asthma and chronic bronchitis evaluated longitudinally in a community population sample of adults. AB - BACKGROUND: Some patients with chronic obstructive pulmonary disease may share the clinical characteristics of those with asthma; their disease is sometimes called "asthmatic bronchitis." Whether there is a difference between asthmatics who do and do not develop chronic bronchitis is not yet clear. We investigated whether asthma and chronic bronchitis may share some "allergic" phenotypes and whether asthmatic individuals who develop chronic bronchitis subsequently have steeper declines in lung function. METHODS: Known risk factors for decline in lung function were analyzed in a representative community population of adults followed up longitudinally since 1972 in Tucson, Ariz, in groups with persistent, newly developed, and past diagnoses of asthma and chronic bronchitis. We evaluated contributions of initial level of forced expiratory volume in 1 second (FEV1), reversibility with isoproterenol hydrochloride nebulized aerosol bronchodilator treatment, percentage of blood eosinophils to determine eosinophilia, and IgE level. RESULTS: The concurrence of chronic bronchitis and asthma is associated with a steeper decline in FEV1 than is asthma as the sole diagnosis. Asthmatics (those with persistent asthma with and without chronic bronchitis) had the greatest prevalence of increased reversibility with isoproterenol therapy and with eosinophilia. The prevalence of eosinophilia was also high in those with newly diagnosed chronic bronchitis without asthma; however, this was not the case in those with persistent chronic bronchitis without asthma. Larger bronchodilator responses were related to steeper declines in FEV1, both in persistent asthma and in chronic bronchitis. CONCLUSIONS: Bronchodilator response and eosinophilia are generally believed to be hallmarks of asthma. We show that these characteristics may be present in chronic bronchitis as well. The presence of a large (> 25%) bronchodilator response is associated with a steeper decline in FEV1. PMID- 7794089 TI - Outcome of hypothyroidism caused by Hashimoto's thyroiditis. AB - BACKGROUND: Hypothyroidism is a common condition that is frequently irreversible and requires lifelong thyroid replacement therapy. OBJECTIVE: To assess the incidence and factors that can predict reversibility of hypothyroidism caused by Hashimoto's thyroiditis. METHODS: We studied 79 patients in whom Hashimoto's thyroiditis was diagnosed according to suggestive cytologic features and/or the presence of thyroid antibodies (antimicrosomal antibody titer, > or = 1:1600; antiglobulin antibody titer, > or = 1:400). All patients were initially hypothyroid (serum total thyroxine level, 83.5 +/- 28.6 nmol/L [6 +/- 2 micrograms/dL]; thyrotropin level, 24.7 +/- 28.3 mU/L). Levothyroxine sodium was then administered for 1 year to normalize results of thyroid blood tests. Thereafter, the treatment was stopped for 3 weeks and serum thyrotropin and total thyroxine concentrations were determined. RESULTS: After withdrawal of levothyroxine treatment, thyroid blood tests showed that the degree of hypothyroidism worsened in 20 patients, remained unchanged in 40, and improved in 19. Nine patients (11.4%) did show normalization of the thyroid blood tests. Before treatment, the presence of the following in a patient--of a goiter that is 35 g or larger, thyrotropin levels greater than 10 mU/L, and an anamnestic familial incidence of thyroid disease--was clearly associated with an increased incidence of recovery of normal thyroid function (relative risk, 5.4; 95% confidence interval, 2.8 to 10.7; P < .0002). CONCLUSIONS: Our results confirm that hypothyroidism caused by Hashimoto's thyroiditis is not always permanent. The presence of a larger goiter and high thyrotropin levels at the time of diagnosis, associated with a familial incidence of thyroid disease, may be related to an increased incidence of hypothyroidism remission. PMID- 7794090 TI - Usefulness of patient interview in bleeding disorders. AB - BACKGROUND: It is not known which questions in a medical interview are most informative for diagnosing mild bleeding disorders, and what the value is of the entire interview in screening for hemostatic disorders. METHODS: A questionnaire was sent to 222 patients with a proven bleeding disorder, to 134 patients suspected of a bleeding disorder but whose hemostasis proved normal, and to 341 healthy volunteers. A first comparison, between patients with a bleeding disorder and patients with bleeding complaints whose hemostasis proved normal, mimics the situation in a department of hematology where patients are referred because of complaints. The second comparison, between patients with a proven bleeding disorder and healthy volunteers, may serve as a model for the situation where the interview is used as a screening tool to detect patients with a bleeding disorder in a population where there is no prior suspicion, eg, before surgical intervention. For each question we calculated a univariate odds ratio, multivariate odds ratios, and a positive and negative likelihood ratio. With a receiver operating characteristic curve analysis we evaluated the value of a simple vs an elaborate interview. RESULTS: Ninety-two percent of the questionnaires were returned. For both comparisons the most informative questions were questions about bleeding disorders in the family and traumatic events, with the exception of delivery. Noninformative questions were frequent gumbleeds and blood in the urine. A receiver operating characteristic curve analysis revealed that a simple interview has a high discriminating power in a screening situation, whereas in a referred situation even an elaborate interview has a low performance. CONCLUSIONS: A simple interview is useful as a screening tool for the dentist or surgeon. In a specialized hematology center with referred patients, however, the interview is of little value in identifying patients with a bleeding disorder. PMID- 7794091 TI - A prospective study of effects of weight cycling on cardiovascular risk factors. AB - BACKGROUND: The possible adverse health effects of weight cycling (weight loss followed by weight regain) have been the subject of recent concern. To determine whether such weight cycling negatively influences cardiovascular risk factors, 153 overweight individuals were followed up prospectively through a 30-month weight loss and maintenance program. METHODS: Subjects were divided into seven groups according to their weight-change patterns during this 30-month study (steady weight loss of different magnitudes, weight gain, no change in weight, and different weight-cycling patterns). These weight-change groups were compared with regard to lipid levels, blood pressure measurements, waist-to-hip ratio, and percent body fat at 0, 6, 12, 18, and 30 months. RESULTS: No adverse effects of weight cycling on any of the cardiovascular risk factors were observed. Subjects who initially lost 9.0 kg or more and then regained it did not differ from those who had no change in weight with regard to any cardiovascular risk factor at month 30. Subjects who gained weight during the 30-month interval increased their risk factors, those who lost weight decreased their risk factors in proportion to the magnitude of weight loss, and, in general, cardiovascular risk factors at month 30 were related to the net weight loss achieved and not the route taken to achieve the weight loss. CONCLUSIONS: This study showed no negative effects of weight cycling on cardiovascular risk factors and confirmed previous findings of positive effects of weight loss on risk factors. Therefore, overweight individuals should be encouraged to lose weight and then maintain their weight loss. PMID- 7794092 TI - Overuse of the indwelling urinary tract catheter in hospitalized medical patients. AB - BACKGROUND: The indwelling urinary tract catheter (IUTC) is an important aspect of medical care. We studied the prevalence of the unjustified use of the IUTC in hospitalized medical patients and identified situations associated with its unjustified use. METHODS: This prospective study involved 202 patients admitted to either the medical intensive care unit (n = 135) or the medical floors (n = 67) of a tertiary care university hospital who were catheterized during the hospital admission. An independent observer assessed the indication of initial catheterization by chart review and interview with the patient and the nurse. The need for continued catheterization was assessed daily by the same observer. The proportion of unjustified IUTC placement was determined using the study guidelines. Complications as a direct consequence of catheter use were recorded. RESULTS: Of the 202 patients who were studied, the initial indication for the placement of an IUTC was found to be unjustified in 21% (95% confidence interval [CI], 15% to 27%). Continued catheterization was unjustified in 47% (95% CI, 42% to 57%) of 912 patient-days with IUTC studied. In the medical intensive care unit, 64% (95% CI, 58% to 70%) of the total unjustified patient-days with IUTC resulted from its excessively prolonged use for monitoring urine output. Urinary incontinence was found to be the major cause of unjustified initial ([52%] 95% CI, 32% to 74%) and continued ([56%] 95% CI, 50% to 62%) use of IUTC in the noncritical care areas. Catheter-related urinary tract infection requiring intravenous antibiotics or continuous bladder irrigation with amphotericin B was observed in 5% of the patients. CONCLUSIONS: The IUTCs are significantly overused in hospitalized medical patients and careful attention to this aspect of medical care may reduce catheter-related complications by primary prevention. PMID- 7794093 TI - Morning report. A survey of resident attitudes. AB - BACKGROUND: Morning report is a time-honored tradition of most internal medicine residency programs. Despite its ubiquity, residents' attitudes regarding morning report have not been investigated. METHODS: Using a 44-item questionnaire, we surveyed residents in an academic internal medicine training program working in five teaching hospitals on the processes of teaching and learning during morning report. RESULTS: Among 74 residents completing the survey (100%), morning report was ranked as the most valuable of six educational activities. Residents preferred discussing new cases, with time equally divided between "great" cases and common problems, an interactive discussion with open-ended questions, and a Socratic teaching style. Seventy-two percent stated that attending physicians should be chosen from among the best teachers. General medical knowledge (90%), an ability to ask effective questions (86%), and good interpersonal skills (84%) were identified as the most important attending physicians' attributes. Discussions of basic science, use of anecdotes, and subspecialty knowledge were not considered highly desirable characteristics. Attending physicians with limited knowledge (41%) were viewed as the major obstacle to effective teaching while provocative attending physicians (52%) were considered as being most valuable to the learning experience. CONCLUSIONS: Residents believed that the morning report was a valuable educational experience. They preferred clinically based, open-ended interactive discussions led by attending physicians with a broad knowledge base. These findings underscore the importance of morning report in general, and the role of attending physicians in particular, in medical education. PMID- 7794094 TI - Hypoalbuminemia in hospitalized patients with community-acquired pneumonia. AB - BACKGROUND: Hypoalbuminemic patients admitted to the hospital for community acquired pneumonia have increased mortality and morbidity. The aim of this study was to investigate the reasons for hypoalbuminemia in these patients. METHODS: During a 12-month period, all patients aged 50 to 85 years (with the exception of immunocompromised patients) with community-acquired pneumonia who were admitted to the Department of Infectious Diseases at Danderyd Hospital, Stockholm, Sweden, were included in a prospective study. The population studied consisted of 97 patients with a mean age of 69.6 years. The patients' nutritional status, including weight, history of weight loss, body mass index, and triceps skinfold thickness, was assessed on admission, as well as at two follow-up visits 8 weeks and 6 months after discharge from the hospital. Blood samples were drawn on admission, during the time in the hospital, and at the follow-up visits. Laboratory tests performed included the following: plasma proteins, albumin, transthyretin and transferrin, alpha 1-antitrypsin, orosomucoid, haptoglobin, C reactive protein, and interleukin-6. RESULTS: No correlation was found between the serum albumin levels and the nutritional measurements. The serum albumin levels correlated positively with the transthyretin and transferrin levels, and inversely with the acute-phase proteins. CONCLUSIONS: The inflammatory reaction is the main reason for depressed serum albumin levels in elderly patients with pneumonia. The study results do not support the use of nutritional supplementation to alter the clinical outcome in these patients. PMID- 7794095 TI - Vancomycin-resistant Enterococcus faecium sepsis following persistent colonization. AB - Vancomycin-resistant enterococci have emerged as important nosocomial pathogens and represent a serious threat to patients with impaired host defenses. We describe a patient with leukemia who developed prolonged colonization with vancomycin-resistant Enterococcus faecium and ultimately died of sepsis due to this multidrug-resistant organism. This case report confirms that colonization with vancomycin-resistant enterococci may last indefinitely and that asymptomatic carriage can lead to invasive infection. PMID- 7794096 TI - Cost-effectiveness and misoprostol. PMID- 7794097 TI - Multidrug-resistant tuberculosis in patients with AIDS. PMID- 7794098 TI - Interobserver variability in interpreting chest radiographs. PMID- 7794099 TI - The control of asymmetric gene expression during Caulobacter cell differentiation. AB - The dimorphic bacterium Caulobacter crescentus provides a simple model for cellular differentiation. Each cell division produces two distinct cell types: a swarmer cell and a stalked cell. These cells possess distinct functional morphologies and differential programs of transcription and DNA replication. The synthesis of a single polar flagellum is restricted to the swarmer pole of the predivisional cell by a genetic hierarchy comprising at least 50 genes whose transcription is regulated by novel and ubiquitous promoters, cognate sigma factors, and auxiliary transcriptional regulators. Chromosome replication is restricted to the stalked cell by a unique chromosome origin of replication that may be regulated by a novel cell-specific transcriptional control system. Phosphorylation signals, DNA methylation, differential chromosome structures, protein targeting, and selective protein degradation are also involved in establishing and maintaining cellular asymmetry. The molecular details of these universal cellular processes in C. crescentus will provide paradigms applicable to many general aspects of cellular differentiation. PMID- 7794101 TI - Purification and characterization of a Synechococcus sp. strain PCC 7942 polypeptide structurally similar to the stress-induced Dps/PexB protein of Escherichia coli. AB - A stable DNA/protein complex having an apparent molecular mass of approximately 150 kDa was purified from nitrate-limited cultures of the cyanobacterium Synechococcus sp. strain PCC 7942. Amino-terminal peptide sequencing indicated that the polypeptide was structurally similar to the Dps protein of Escherichia coli; Dps is also known as the product of the starvation- and stationary-phase inducible gene, pexB. The 150-kDa complex dissociated into a 22-kDa protein monomer after boiling in 2% SDS. The 150-kDa complex preparation had approximately a 10% nucleic acid content and upon dissociation released DNA fragments that were sensitive to S1 nuclease digestion. Immunoblot data indicated that the complex accumulates during stationary phase and during nitrogen, sulfur, and phosphorus limitation. DNA-binding assays indicated that the protein nonspecifically binds both linear and supercoiled DNA. Circular dichroism spectroscopy revealed that the Synechococcus sp. Dps-like protein contains extensive regions of alpha-helical secondary structure. We propose that the 150 kDa complex represents a hexameric aggregate of the Dps-like protein complexed with single-stranded DNA and serves to bind a portion of the chromosomal DNA under nutrient-limited conditions. PMID- 7794100 TI - The upstream region of the isocitrate lyase gene (UPR-ICL) of Candida tropicalis induces gene expression in both Saccharomyces cerevisiae and Escherichia coli by acetate via two distinct promoters. AB - The upstream region of the isocitrate lyase gene (UPR-ICL, 1530bp) of an n-alkane utilizable yeast, Candida tropicalis, induced gene expression in another yeast, Saccharomyces cerevisiae, when the yeasts were grown on acetate. Surprisingly, UPR-ICL displayed the same regulatory function in the bacterium Escherichia coli when grown on acetate. We determined the interesting nucleotide sequence of UPR ICL. The deletion analysis of UPR-ICL in both cells revealed the presence of two distinct promoters: one was localized at -394 to -379 and regulated gene expression in S. cerevisiae; the other was located near the initiation codon and regulated gene expression in E. coli. The two promoter sequences were similar, but not identical to regulatory elements that have been previously reported in S. cerevisiae and E. coli, respectively. Accordingly, the possibility of novel regulatory mechanisms could not be excluded. This is an interesting example of the presence of distinct cis-acting regulatory elements responsible for the induction of gene expression in one gene by acetate in both S. cerevisiae and E. coli. Preservation of such promoters through evolution is also discussed. PMID- 7794102 TI - Chemical characterization of two lipopolysaccharide species isolated from Rhizobium loti NZP2213. AB - Phenol-water extraction of Rhizobium loti NZP2213 cells allowed a simultaneous isolation of two structurally different lipopolysaccharides from the aqueous (LPS W) and phenol (LPS-P) phase that differed in their sodium deoxycholate-PAGE pattern and composition. LPS-W showed a profile indicating an R-type LPS; LPS-P had a cluster of poorly resolved bands in the high-molecular-weight region. LPS-P contained large amounts of 6-deoxy-L-talose (6dTal), and a small amount of 2-O methyl-6-deoxy-talose (molar ratio approximately 30:1), both of which were completely absent in LPS-W. Methylation analysis gave only one major product, 2,4 di-O-methyl-6dTal, indicating that the O-chain is composed of a homopolymer of 1,3-linked 6dTal, having the methylated 6dTal (2-O-Me-6dTal) probably localized at the non-reducing end of the O-chain. This homopolymeric O-chain was additionally O-acetylated, as evidenced by GC-MS and by 13C NMR analysis. The lipid A moieties of both LPS-W and LPS-P showed almost identical composition, with six different 3-OH fatty acids and with two, so far not described, long chain 4-oxo-fatty acids, all being amide-linked, and with 27-OH-28:0 as the main ester-linked fatty acid. Lipid A was of the lipid ADAG-type, i.e., having a (phosphorylated) 2,3-diamino-2,3-dideoxy-D-glucose-containing lipid A backbone. Lipid ADAG is widespread among species of the alpha-2 group of Proteobacteria, but has so far not been encountered in any other rhizobial or agrobacterial species. PMID- 7794104 TI - Homosexuality, type 1: an Xq28 phenomenon. AB - Despite the absence of phenotypic manifestations in alternating generations characteristic of X-linked disorders, a thesis is presented that a major type of Kinsey grades 5 and 6 male homosexuality is determined by a gene in the Xq28 region. A total of 133 families in 78 kinshps of male and female homosexual probands, in addition to 116 families (including those of 40 famous homosexuals) from the literature, revealed an unbalanced secondary sex ratio in the maternal generation of male, but not of female, homosexuals. On the maternal side, in this study, the ratio of all uncles to all aunts of 90 males homosexuals was 132/209, chi 2 = 8.52, p = 0.004. On the maternal side for the total of all sources, the ratio of uncles to aunts of male homosexuals was 241/367, chi 2 = 13.20; p < 0.0001. The male/female ratio of the total number of maternal sibships bearing homosexuals (310/628: 0.491) was a measure of fetal wastage of the mothers' male sibs; 49%. This ratio was very close to that of the total number of children born to fathers affected with any one of nine Xq28-linked male semilethal conditions (255/508: ratio 0.556); for the difference between the two populations chi 2 = 0.859, p = 0.354. The male/female ratio of the total number of children born to female carriers of any one of these same conditions (1,232/1,062: ratio 1.16), chi 2 = 13.8 p < or = 0.0001, is close to that of the total number of children in homosexual sibships: 511/413, chi 2 = 10.4, p = 0.005. Between the number of children born to Xq28 mothers and to those born of mothers of homosexuals chi 2 = 0.581, p = 0.446. One may readily surmise that the maternal influence so often related to homosexuality may lie in the mother being a genetic carrier, with traits thereto associated. In this study, 65% of the mothers of homosexuals had no or only one live-born brother. Additional support for a genetic hypothesis is found in the occurrence of multiple instances--almost exclusively among maternal relatives--of infertility, spontaneous abortions, miscarriages, stillbirths, remaining single past age 30, and suicide. Of 109 male and 43 female homosexual index cases in the present series there were 6 instances of brother/sister homosexual sibships.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7794105 TI - Surgical sex reassignment: a comparative survey of international centers. AB - The Harry Benjamin International Gender Dysphoria Association's Standards of Care (Walker et al., 1985) set out minimum standards for the selection of patients for sex reassignment surgery. This survey reports on the standard and policies actually used by clinics in Europe and North America, including their areas of agreement and disagreement with the Standards. To our knowledge, there has been only one prior survey of gender clinic policies, and that was restricted to European treatment facilities. The present survey is aimed at primary caregivers in the medical community; however, it may also be of use to administrators in responding to increasing demands for accountability from special interest groups and from government, with their often divergent agendas. It is our hope that this survey will begin the process of developing more uniform standards of care. PMID- 7794103 TI - Cell-surface properties of the food- and water-borne pathogen Aeromonas hydrophila when stored in buffered saline solutions. AB - Aeromonas hydrophila, a ubiquitous inhabitant of aquatic environments, commonly expresses several cell-surface properties that may contribute to virulence. Since many aquatic microorganisms in hostile environments can withstand starvation conditions for long periods, we examined the effect of storage under nutrient poor conditions on the expression of cell-surface properties of this pathogen. Phenotypes studied were: (1) cell-surface hydrophobicity and charge, and (2) the ability to bind connective-tissue proteins and lactoferrin. Our results suggest that the response of A. hydrophila to nutrient-poor conditions is regimen specific. Generally, A. hydrophila cells became more hydrophobic and significantly increased their ability to bind the iron-binding glycoprotein lactoferrin when the bacterium was stored under nutrient-poor conditions; however, under these conditions, the cells seemed to lose their ability to bind connective-tissue proteins. PMID- 7794106 TI - Psychosexual functioning of partners of men with presumed non-organic erectile dysfunction: cause or consequence of the disorder? AB - In the treatment of couples where the male partners have erectile dysfunction (ED) it often becomes apparent that characteristics of the female partners and of the relationship in general have contributed to the problem. However, this has received little research attention. We investigated female partners of men with ED where no organic cause could be found (n = 34) and partners of men with organically based ED (n = 71) to compare their views on their relationships, sexual function, sexual attitudes, and psychological adjustment. Relationship problems and the psychosexual dysfunctions of vaginismus and dyspareunia were more common in the partners of men with nonorganic ED; they also reported higher levels of sexual interest. Female sexual dysfunctions in the nonorganic ED group had usually preceded the onset of the erectile difficulties. While belief in male sexual myths was substantial in both groups of patients, neither the presence of traditional views on sexuality nor psychological complaints distinguished partners of men experiencing nonorganic ED from those with organic ED. Relationship problems, female psychosexual dysfunction, and the possible effect of relatively high levels of female sexual interest may contribute to the onset, exacerbation, and maintenance of ED. These should be addressed during assessment and treatment of couples in which the male partners have erectile difficulties. PMID- 7794107 TI - Sex without emotional involvement: an evolutionary interpretation of sex differences. AB - Two samples of male (n = 243) and female (n = 298) college students completed sexual surveys, and in-depth, oral interviews were conducted with 28 highly sexually active female college students. Findings supported five predictions derived from evolutionary (parental-investment) theory. Even when females voluntarily engaged in low-investment copulation, coitus typically caused them to feel emotionally vulnerable, and to have thoughts expressing anxiety about partners' willingness to invest. For females, increasing numbers of partners correlated positively with the incidence of these feelings and thoughts; for males, these correlations were negative. Females' attempts to continue regular coitus when they desired more investment than partners were willing to give produced feelings of distress, degradation, and exploitation despite acceptance of liberal sexual morality. Increasing numbers of partners did not mitigate these reactions in females and may exacerbate them. Multiple-partner females developed techniques for dealing with their emotional reactions to low-investment copulation: They frequently tested their partners for signs of ability and willingness to invest (e.g., dominance, prowess, jealousy, nurturance), and they limited or terminated sexual relations when they perceived partners' investment as inadequate. Results were consistent with the view that the emotional motivational mechanisms that mediate sexual arousal and attraction are sexually dimorphic. PMID- 7794108 TI - Maternal sexuality during pregnancy and after childbirth in Muslim Kuwaiti women. AB - The sexuality of Kuwaiti Muslim women before pregnancy, during pregnancy, and 6 months after childbirth was studied. A group of 220 women attending the prenatal clinic of the Maternity Hospital Kuwait were randomly selected; 40 (18.2%) declined at the outset, 10 (4.6%) withdrew due to miscarriage and 10 (4.6%) due to failure to attend interviews. The semistructured interview was conducted by a female obstetrician at 4-week intervals starting from 12 weeks pregnancy to 6 months after childbirth. The study led to the following observations: (i) All the women were religious and abided by the Islamic rules and way of life. (ii) The diagnosis of pregnancy led to a decline in sexuality that continued throughout the pregnancy, with a second and early third trimester increase in sexuality but still below the prepregnancy baseline. (iii) Each woman had a consistent pattern of sexuality during pregnancy reflecting her prepregnancy level of sexuality. (iv) Younger age group, multiparity, low-level of education, lesser duration of marriage, and intention of breast-feeding characterized the sexuality pattern positively, as did attitudes towards sexuality during pregnancy and after childbirth. Breast-feeding mothers exceeded their prepregnancy level of sexuality earlier than bottle-feeding mothers. PMID- 7794109 TI - ICP27 immediate early gene, glycoprotein K (gK) and DNA helicase homologues of infectious laryngotracheitis virus (gallid herpesvirus 1) SA-2 strain. AB - A 4.8 kilobase segment located at the left-terminal in the unique long (UL) region of infectious laryngotracheitis virus (ILTV) SA-2 strain contained three open reading frames (ORFs). The first of 421 amino acids (aa) was located at map units 0.065 to 0.07, and its predicted 48 kiloDaltons (kDa) protein product has significant homology to the immediate early regulatory protein ICP27 (UL54) of herpes simplex virus type-1 (HSV-1), to varicella-zoster virus (VZV) ORF4 and to equine herpesvirus 1 (EHV-1) ORF5. The zinc finger conserved in the C-terminal of the proteins from HSV-1, VZV and EHV-1, is poorly conserved in ILTV homologue. The second ORF of 336 aa, located at map units 0.075 to 0.08, has a predicted molecular weight (MW) of 38 kDa with significant homology to glycoprotein K (gK) of HSV-1 (UL53), ORF5 of VZV and ORF6 of EHV-1. ILTV gK has features characteristic of a membrane-bound glycoprotein. The 3' region of a third ORF was located at map units 0.08 to 0.095. Translation of the sequence revealed significant homology to the 3'-region of the DNA helicase-primase complex protein (UL52) of HSV-1, ORF6 of VZV and ORF 7 of EHV-1. Northern blot analyses were used to characterize the ILTV ICP27, gK and DNA helicase mRNAs. The data revealed that ILTV ICP27 is an immediate early gene that encodes a 1.6 kb mRNA, ILTV gK encodes a late transcript of 1.8 kb, while ILTV DNA helicase encodes a late transcript of 3.7 kb. PMID- 7794110 TI - The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies. AB - The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3 peptides corresponding to field isolates were highly immunogenic but failed to induce neutralizing or gp120-precipitating Abs. On the contrary, V3 peptide corresponding to the laboratory strain HXB2 induced HIV neutralizing, gp120-precipitating immune serum. In conclusion, these data suggest a participation of the V3 domain in the immunoselection of escape virus, and that V3 on early field virus is less accessible to NA than that on laboratory strains. PMID- 7794112 TI - Serological recognition of feline infectious peritonitis virus spike gene regions expressed as synthetic peptides and E. coli fusion protein. AB - Cats exposed to feline infectious peritonitis virus (FIPV) or feline enteric coronavirus (FECV) cannot be differentiated by serological analysis. Three synthetic peptides and an E. coli recombinant fusion protein generated from FIPV 79-1146 spike gene sequence were produced. Coronavirus positive cat sera reacted to peptide aa 950-990 but were non-reactive to aa137-151 and aa 150-180 peptides as demonstrated by ELISA. Amino acid sequence 97-222 expressed as a galk fusion protein in E. coli was tested against coronavirus positive cat sera by western blot analysis. Only sera from cats exposed to the FIPV type-II strains DF-2 or 79 1146 that were exhibiting signs of FIP recognized the fusion protein. Sera from FECV exposed cats did not recognize the 97-222 fusion protein in western blot analysis. PMID- 7794111 TI - Genetic recombination of pseudorabies virus: evidence that homologous recombination between insert sequences is less frequent than between autologous sequences. AB - We studied in vivo recombination between a thymidine kinase (TK) negative, glycoprotein E (gE) negative, attenuated strain and a virulent strain of pseudorabies virus (PRV) in pigs. To simplify the detection of recombination we inserted different but overlapping (375 bp) parts of the E1 gene of classical swine fever virus into the gG locus of both virus strains. Recombination between the E1 sequences of these viruses results in reconstitution of the complete E1 coding sequence and expression of the E1 protein. Since E1 is highly immunogenic, we expected to detect in vivo recombination in co-inoculated pigs by the presence of serum antibodies against E1. However, after co-inoculation of pigs with high doses of both virus strains, we were unable to detect antibodies against E1, suggesting that in vivo recombination did not occur or remained below the detection limit. Analysis of individual progeny viruses showed that 13 out of 995 (1.3%) possessed a recombinant TK-negative gE-positive phenotype. In contrast, no E1-positive viruses were detected among 5000 analyzed. This result showed that in vivo recombination between the two virus strains did occur, but was much more frequent between the TK and gE loci than between the E1 sequences. Similar results were obtained in in vitro recombination experiments in which possible growth differences between the various virus strains were excluded. The different recombination frequencies could not be attributed to the difference in distance of the genetic loci since recombination between mutations at a distance of 266 bp in the TK gene occurred as frequent as recombination between the TK and gE genes which are separated by approximately 60 kilobasepairs. These results indicate that some property of the E1 sequence and/or the location of the E1 sequence within the PRV genome affects the frequency of recombination. PMID- 7794114 TI - Distribution of antibodies to porcine circovirus in swine populations of different breeding farms. AB - An enzyme linked immunosorbent assay (ELISA) was developed for mass antibody screening to porcine circovirus (PCV) in pig herds of different age groups and of different husbandries. Infection with PCV was found to be common in all swine herds tested, with only one exception, a herd at a small farm. Statistically, the percentage of PCV negative sera decreased and titer levels increased with increasing age of the pigs. Within individual age groups, differences were found to exist between different husbandries. No correlation was detected between antibody levels and reproductive disorders in the herds. PMID- 7794113 TI - The antiviral activity of tumour necrosis factor on herpes simplex virus type 1: role for a butylated hydroxyanisole sensitive factor. AB - We have previously shown that specific antibodies (Mab 32/Ab 301) against tumour necrosis factor (TNF) enhance its antiviral activity in vaccinia virus-infected mice. In the present study, TNF alone was found to have antiviral activity against herpes simplex virus-1 (HSV-1). Antibody enhancement was found, both in vivo and in vitro, at lower TNF doses. The magnitude of the TNF-induced antiviral response was dependent upon the genetic background of the mouse. C57BL/6 mice were very sensitive to the antiviral activity of TNF, which was inhibited by the free radical scavenger butylated hydroxyanisole (BHA). TNF plus Mab 32 induced a significant antiviral effect in L929 cells which was associated with pronounced CPE. The CPE was largely reversed in the presence of BHA, and furthermore, TNF antiviral activity was significantly reversed in the presence of BHA. Specific inhibitors of nitric oxide synthetase, lipoxygenase or cyclo-oxygenase did not influence either the CPE or growth kinetics of HSV-1, suggesting that neither reactive nitrogen intermediates nor arachidonic acid metabolites were involved in the antiviral mechanism of TNF. This, together with observed increases in Cu/Zn SOD levels in virus infected cells, suggests that reactive oxygen intermediates may have a role in the direct control of HSV-1 growth and that free radicals may play a part in the antiviral activity induced by TNF. PMID- 7794116 TI - Large scale purification of rubella virus and the isolation of native viral core protein. AB - A number of structural analyses of viruses are dependent on the availability of purified virus and of pure viral components in milligram amounts. In order to allow such analyses of the Rubella togavirus we have identified a virus-cell system which produces large amounts of Rubella virus in tissue culture and we have developed a rapid and efficient procedure of Rubella virus purification which involves adsorption and elution of virus to fixed erythrocytes. Furthermore, we describe a procedure which allows the extraction of native core protein from viral cores and its chromatographic purification. PMID- 7794115 TI - Phylogenetic analyses of the putative M (ORF 6) and N (ORF 7) genes of porcine reproductive and respiratory syndrome virus (PRRSV): implication for the existence of two genotypes of PRRSV in the U.S.A. and Europe. AB - The putative membrane (M) protein (ORF 6) and nucleocapsid (N) protein (ORF 7) genes of five U.S. isolates of porcine reproductive and respiratory syndrome virus (PRRSV) with differing virulence were cloned and sequenced. To determine the genetic variation and the phylogenetic relationship of PRRSV, the deduced amino acid sequences of the putative M and N proteins from these isolates were aligned, to the extent known, with other PRRSV isolates, and also other members of the proposed arterivirus group including lactate dehydrogenase-elevating virus (LDV) and equine arteritis virus (EAV). There was 96-100% amino acid sequence identity in the putative M and N genes among U.S. and Canadian PRRSV isolates with differing virulence. However, their amino acid sequences varied extensively from those of European PRRSV isolates, and displayed only 57-59% and 78-81% identity, respectively. The phylogenetic trees constructed on the basis of the putative M and N genes of the proposed arterivirus group were similar and indicated that both U.S. and European PRRSV isolates were related to LDV and were distantly related to EAV. The U.S. and European PRRSV isolates fell into two distinct groups, suggesting that U.S. and European PRRSV isolates represent two distinct genotypes. PMID- 7794117 TI - Preferential selection of VP7 gene from a parent rotavirus strain (SA11) in sequential passages after mixed infection with SA11 and SA11-human rotavirus single-VP7 gene-substitution reassortants. AB - We studied the competitive growth among SA11-L2(G3) and its single-human VP7 gene substitution reassortants SA11-L2/KU-R1(G1) and SA11-L2/DS1-R1(G2), which have the genetic background of SA11-L2, during sequential passages after mixed infection. When the same infectious units (m.o.i. of 5 p.f.u./cell) of SA11-L2 and a reassortant SA11-L2/KU-R1 were inoculated onto and passaged in MA104 cells, 88% of the virus clones isolated from the culture fluid at the 3rd passage belonged to G3, and all the clones from the 10th passage had G3 specificity. Even when SA11-L2/KU-R1 with titer 10 times higher than that of SA11-L2 was used in the coinfection, the predominance of clones with G3-VP7 was observed. Although G2 clones slightly surpassed G1 clones in number in the mixed culture of SA11-L2/KU R1 and SA11-L2/DS1-R1, G3 clones predominated in the virus progeny from a mixed culture infected with the same titers of SA11-L2, SA11-L2/KU-R1, and SA11-L2/DS1 R1. However, no significant difference in viral growth was detected among SA11-L2 and the two reassortants. PMID- 7794118 TI - Serial passage in tissue culture of mixed foot-and-mouth disease virus serotypes. AB - The foot-and-mouth disease (FMD) virus field specimen SAU/8/88 was previously shown to consist of a mixture of O and Asia 1 serotypes [15]. In this study, plaques representing the O and Asia 1 components isolated from the original epithelial virus suspension were used to construct mixtures of known ratios, and these were serially passaged in tissue culture. After each passage, the ratio of O to Asia 1 virus was calculated. The two virus populations were shown to be cycling through time. This cycling phenomenon has not been described before for FMD virus in tissue culture, but is consistent with current population theory. PMID- 7794119 TI - Immunization with glycoprotein C of equine herpesvirus-1 is associated with accelerated virus clearance in a murine model. AB - The glycoprotein C (gC) gene of equine herpesvirus-1 (EHV-1) was expressed in insect cells by a recombinant baculovirus as several products with apparent molecular weights of 66 kDa-80 kDa. The baculovirus EHV-1 gC products were recognised by monoclonal antibody and by EHV-1 convalescent equine sera, indicating conservation of antigenic determinants and confirming this glycoprotein as a target for the equine immune system. Mice immunized with recombinant EHV-1 gC showed accelerated clearance of EHV-1 from respiratory tissues following intranasal challenge. Virus clearance was accompanied by virus specific antibodies and by cell mediated immune responses measured by a delayed type hypersensitivity reaction and lymphocyte stimulation by killed EHV-1 as antigen. PMID- 7794120 TI - A model for the membrane topology of the NS3 protein as predicted from the sequence of segment 10 of epizootic haemorrhagic disease virus serotype 1. AB - Segment 10, encoding nonstructural proteins 3 (NS3) and 3a (NS3a) of epizootic haemorrhagic disease virus serotype 1 (EHDV-1) was sequenced. Computer motif recognition programs were used for interpretation of the sequence data to predict a structure for NS3. Integral membrane protein theories were then applied to produce a general topological model for the EHDV-1 NS3 protein. Homology was observed between EHDV-1 NS3 integral membrane motifs and those similarly observed in the cognate proteins of other orbiviruses. PMID- 7794121 TI - Fructose-induced hypertension, hypertriglyceridemia and elevated cytosolic calcium in rats: prevention by deuterium oxide. AB - We examined the effect of 5% deuterium oxide (D20) in drinking water on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and plasma insulin, glucose and triglycerides in rats with fructose-induced hypertension. Eighteen male Wistar-Kyoto (WKY) rats, age 8 weeks, were divided into 3 groups of 6 animals each. Animals in group I were given water; group II, 8% fructose and group III, 8% fructose + 5% D20 as their drinking water for the next 15 weeks. Systolic blood pressure in the fructose treated rats was significantly higher (p < 0.01) than in animals on water after 2 weeks and remained higher throughout the study. At 15 weeks, systolic blood pressure, platelet cytosolic calcium, aortic calcium uptake and plasma glucose, insulin and triglycerides were significantly higher (p < 0.01) in the fructose treated rats compared with rats from other groups. Deuterium oxide given together with fructose prevented development of high blood pressure and the associated increase in platelet cytosolic calcium, aortic calcium uptake and plasma triglycerides. D20 treatment did not prevent fructose induced increases in plasma insulin and glucose. The parallel increase in systolic blood pressure, cytosolic free calcium, and in vascular calcium uptake suggests that an increased cytosolic free calcium is involved in the pathophysiology of hypertension. D20 prevents this hypertension by normalizing cytosolic free calcium. PMID- 7794122 TI - Anticoagulant effects of warfarin and kinetics of K vitamins in blood and feces. AB - Patients (40 cases) were treated with daily dosage of warfarin of 2-7 mg after being undergone artificial valve replacements. Twenty one days after administration of warfarin, we examined the patients for kinetics of K vitamins and vitamin K-dependent coagulation factors in blood, and intestinal flora in feces, as well as the relationship between K vitamins and coagulation activity. The following results were obtained. (1) In warfarin-administered patients (Group B), blood levels of vitamin K1 and menaquinone-7, a vitamin K2 homologue, were similar to those in non-warfarin-administered patients. Therefore, administration of warfarin did not significantly decreased the levels. (2) In patients selected randomly from Group B (Group C), the vitamin K1 level in feces was higher than that in non-warfarin-administered patients. The menaquinone-7 level in feces was similar to that in non-warfarin-administered patients. For the total counts of bacteria and the detection rate of vitamin K2-producing bacteria, there was no significant difference between Group C and non-warfarin-administered patients. (3) The above mentioned results of (1) and (2) suggest that it is important for development of anticoagulant effects by warfarin to inhibit conversion from vitamin K1 to reduced vitamin K1, as well as to inhibit the reducing process from vitamin K1-epoxide to vitamin K1. (4) Vitamin K1-epoxide, a metabolite of vitamin K1, appeared in blood after administration of warfarin; there was a lower correlation between the blood level of vitamin K1-epoxide and the warfarin dosage. Further, PIVKA-II appeared in blood after administration of warfarin; there was a inverse lower correlation between the level of PIVKA-II and HPT, and between PIVIKA-II and TT. In conclusion, it has been clarified that vitamin K1 epoxide and PIVKA-II are useful parameters to evaluate anticoagulant effect of warfarin. PMID- 7794123 TI - Interleukin-4 inhibits human smooth muscle cell proliferation. AB - Although proliferation of smooth muscle cells is a key event in the pathogenesis of atherosclerosis, the signals which regulate this proliferation are not fully understood. It is likely that proliferation is regulated by cytokines released by cells found in the plaque, such as T cells. In this study we report that the T cell-derived cytokine, interleukin-4 (IL-4), can inhibit proliferation of cultured human umbilical artery smooth muscle cells. Maximum inhibitory effect was achieved at IL-4 concentrations of 20 U/ml or greater. In addition, the data showed that IL-4 acted early in the G1 phase of the cell cycle, thereby preventing cells from entering S phase. The mechanism of IL-4 inhibition did not appear to involve stimulation of prostanoid synthesis since similar data were obtained when experiments were performed in the presence of a cyclooxygenase inhibitor. We propose that IL-4 may act as a protective factor released by T cells in an atherosclerotic lesion in order to minimise the size of the plaque. PMID- 7794124 TI - The influence of rate of cell entry to S phase on the labelling index of human buccal epithelium. AB - The physiological basis of the circadian rhythm in cell kinetics in human epithelia remains unclear. A 24-h periodicity in the labelling index (LI) of human buccal epithelium has been demonstrated previously. A double-labelling technique in vitro using tritiated deoxythymidine was used here to examine fluctuations in the time spent in S phase (Ts) and the rate of cell entry to S phase (S influx). While the range in Ts values was limited (5.1-6.9 h), influx to S phase ranged from 0 to 1.26% per hour at six different time periods. An increase in the S influx was apparent around 18:00 h leading to a peak LI 4 h later. These preliminary data indicate that the most likely kinetic mechanism related to circadian variations in LI is a variable G1-S influx at this site. PMID- 7794125 TI - Inhibition by thiocyanate of muscarinic-induced cytosolic acidification and Ca2+ entry in rat sublingual acini. AB - Thiocyanate (SCN-) plays a critical part in an oral antimicrobial system by acting as a substrate for peroxidases. Salivary glands concentrate SCN- from blood up to 5 mM in saliva; however, the influence of SCN- on salivary acinar cell function is unknown. The present study examined the effects of SCN- on the regulation of cytosolic pH (pHi) and free Ca2+ concentration ([Ca2+]i) in rat sublingual mucous acini using the pH- and Ca(2+)-sensitive fluorescent indicators, 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein and fura-2, respectively. SCN- induced a concentration-dependent inhibition of the carbachol stimulated cytosolic acidification (K1/2, approx. 1.4 mM SCN-). Cytosolic pH recovery from an acid load was not changed by substitution of Cl- by SCN-, suggesting that Na+/H+ exchange activity was not affected by SCN-. SCN- did not alter the initial carbachol-stimulated increase in [Ca2+]i; however, the sustained [Ca2+]i increase was inhibited by > 65% (K1/2, approx. 1.0 mM SCN-). Furthermore, SCN- prevented the carbachol-stimulated Mn2+ influx, indicating that it inhibits the divalent-cation entry pathway. Consistent with decreased Ca2+ mobilization being involved in the blockade of the agonist-induced acidification by SCN-, only total replacement of Cl- with SCN- significantly inhibited the acidification induced by the Ca2+ ionophore ionomycin. The permeability to SCN- through the Ca(2+)-dependent Cl- channels was 5.2-fold higher than the permeability to Cl-. These results suggest that inhibition of the agonist-induced cytosolic acidification by high-concentration SCN- may be mediated by both competitive inhibition of HCO3- efflux and by blockade of Ca2+ influx. PMID- 7794126 TI - Mandibular growth rates in human fetal development. AB - A morphometric analysis of changing proportions in the developing mandible was undertaken in 18 human embryos and fetuses of both sexes (developmental age from 8 to 14 weeks, crown-rump length, CRL, from 34 to 110 mm), previously cleared and stained with a specific method for bone (alizarin red S). Reference points were located on the mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN), gonion (GO), superior symphyseal point (SSP), for measuring linear dimensions, i.e. Pcl-GN, Pcl-Pco, Pco-GN, GO-GN, SSP-GN. The gonial (Pcl-GO-GN) and the (Pcl-GN-Pcl) angles were also measured. All linear dimensions were correlated with the CRL by bivariate allometry (1n y = 1n a+b 1n x): they all grew with positive allometry, except GO-GN with isometry. The mandibular ramus grew relatively faster than the body, both in length and height, and the greatest growth rate was found for ramus height. The relation between mandibular shape and the craniofacial structures was investigated using scale drawings obtained from photographs of fetal skulls in lateral view. In the youngest fetuses the mandible was prognathic, then became retrognathic. During the period investigated the zygomatic process and squama of the temporal bone were in a lower and more inclined position in relation to the transverse plane passing through the zygomatic arch than in the newborn and adult. This study identifies parameters fitting changing trends in height, length and shape of the human mandible during the prenatal period (8-14 weeks); moreover, it emphasizes that the mandibular growth patterns differ significantly from those of successive development periods. PMID- 7794127 TI - Spatial distribution of epidermal growth-factor transcripts and effects of exogenous epidermal growth factor on the pattern of the mouse dental lamina. AB - The initiation of odontogenesis is characterized by the site-specific proliferation of mandibular epithelium in the formation of the dental lamina. The epidermal growth factor (EGF) gene is expressed in the developing mandible immediately before the appearance of the dental lamina. This expression is necessary for the formation of the dental lamina and subsequent development of teeth. Previous work has demonstrated that retinoids and EGF may interact in the establishment of the pattern of the dentition. In the present study explanted mandibles that were treated with exogenous EGF (40 ng/ml of medium) contained supernumerary buds of mandibular epithelium in the diastema region. These pattern changes were the same as in previous retinoid-treated explants. These results, in addition to the previously reported effects of retinoids on the expression of the EGF gene, support the hypothesis that retinoids and EGF interact in controlling, at least in part, the pattern of the dentition by affecting the pattern of the dental lamina. The spatial distribution of EGF transcripts was also characterized. The location of EGF transcripts in the mesenchyme adjacent to the mandibular epithelium suggests a paracrine mechanism in the stimulation of epithelial proliferation in the formation of the dental lamina. PMID- 7794128 TI - Bone matrix proteins in osteogenesis and remodelling in the neonatal rat mandible as studied by immunolocalization of osteopontin, bone sialoprotein, alpha 2HS glycoprotein and alkaline phosphatase. AB - The neonatal rat mandible was used as a model to study bone formation, mineralization, quiescence, and resorption, using immunolocalization and a variety of tissue-processing techniques. Monospecific antibodies for osteopontin (OPN), bone sialoprotein (BSP), alkaline phosphatase (AP) and alpha 2HS glycoprotein (alpha 2HS-GP) were used on fixed paraffin-embedded tissue, fixed frozen tissue and unfixed frozen tissue. Immunostaining was correlated with mineral content by two procedures, the von Kossa and the morin techniques. Morin fluorescence was used with secondary immunostaining to provide a way of closely correlating bone matrix proteins and matrix mineralization. Co-immunolocalization procedures were used to compare the sites of bone proteins in the matrix. AP was found earliest during osteogenic cell differentiation, appearing in the preosteoblasts, followed by OPN and BSP, which first appeared in osteoblasts. alpha 2HS-GP expression was not observed in cells. The results provide clear evidence for the presence of OPN in osteoid, while BSP and alpha 2HS-GP were confined to the mineralized matrix. Immunostaining of bone proteins is highly technique-dependent: immunolocalization investigations required several methods of approach to ensure adequate demonstration of these proteins in cells and matrix. The results support the contention that osteopontin is multifunctional in bone metabolism, and that alpha 2HS-GP, though produced in the liver, is abundant in bone matrix and may also have a function in bone metabolism. PMID- 7794129 TI - Gene expression of epimorphin in rat incisor ameloblasts. AB - Epimorphin has been recently identified as an important factor in the morphogenesis of epithelial cells. A cDNA encoding epimorphin from skin of newborn mice was cloned by the polymerase chain-reaction technique before the preparation of digoxigenin-labelled cRNA probes. In situ hybridization of longitudinal sections of rat incisors revealed a distinct pattern of expression of epimorphin mRNA in the ameloblast layer. Epimorphin mRNA was detected from the presecretory stage up to the beginning of the maturation stage of amelogenesis. With the identification of this expression by epithelial-derived cells, i.e. ameloblasts, it is thought likely that epimorphin is one of the factors that modulate the differentiation cascade of ameloblasts in the course of amelogenesis. PMID- 7794130 TI - Characterization of cyclic AMP phosphodiesterase isozymes in rat parotid gland. AB - Cyclic AMP phosphodiesterase (PDE) isozymes were isolated and characterized from the soluble fraction of rat parotid gland. Four main peaks containing PDE activity were obtained by Q-Sepharose Fast Flow column chromatography. The four peaks were identified as PDEs I-IV by kinetic properties, molecular-weight analysis and their responses to effectors and inhibitors. PMID- 7794133 TI - Expectations of medical education. PMID- 7794131 TI - Immunoelectron-microscopic study of the localization of fibronectin in the odontoblast layer of human teeth. AB - Indirect immunofluorescence-based studies have shown similarities in the distribution patterns of fibronectin-positive fibrous structures and so-called von Korff fibres. The aim of the present study was to analyse the reactivity of fibronectin in the odontoblast layer of fully developed human teeth by means of immunoelectron microscopy. Between the odontoblasts, discrete and undulatory fibrillar fascicles with peroxidase labelling were observed. They seemed to be in contact with odontoblasts in some areas, while in others they appeared to be intervening between two neighbouring odontoblasts. Higher magnifications of the fibrillar material demonstrated axial periodic staining of about 70 nm. Peroxidase reaction of fibronectin was also recognized along the cell membrane of odontoblasts facing predentine. The fibronectin in fibrillar fascicles observed between odontoblasts would be held in place by the direct molecular interaction with collagen fibrils and contribute to the pulpward migration of these cells and maintenance of their specific morphology. At the distal end of odontoblasts, a tight seal would be maintained by means of odontoblast-fibronectin adhesion. PMID- 7794132 TI - Racemization of aspartic acid in human cementum with age. AB - This study explored the application of the racemization reaction to forensic dental medicine in relation to estimation of age from tooth cementum. Cementum from the cervical two-thirds and the apical one-third of 16 upper incisor teeth gave ratios of D-/L-aspartic acid that correlated highly with actual age, the correlation coefficients being r = 0.993-0.996. For whole cementum from lower central and lateral incisors, first and second premolars (n = 8) the correlation coefficients were r = 0.984-0.997. Incisors gave more reliable results than premolars. The study was extended to compare cementum, enamel and dentine from first premolar teeth of the same individuals. The correlation of the ratio of D /L-aspartic acids with actual age was highest for dentine (r = 0.992), followed by cementum (r = 0.988) and enamel (r = 0.961). These results indicate that the racemization reaction in cementum proceeds in a constant manner, and confirm that cementum remains stable throughout the individual's life. Accurate estimation of age is thus possible when cementum is subjected to the amino-acid racemization method. PMID- 7794134 TI - General practice: a philosophical tour. PMID- 7794135 TI - General practice and the new renaissance. AB - Traditional medical education has tended to emphasise the acquisition of knowledge and analytical skills. But it is the author's belief that this system has some limitations when applied in the general practice situation. Dr Edward DeBono has described an alternative style of thinking that relies fundamentally on perceptive and creative skills; ideas that have great relevance in learning how to apply our acquired knowledge in a meaningful way to the health care of our patients. This paper describes the personal odyssey that led to this realisation. PMID- 7794136 TI - Frank. AB - In medical school we are taught that the 'proper' relationship between doctor and patient is one where the doctor remains aloof and objective. Because of the nature of general practice we often form friendships with our patients. These friendships enrich our professional lives without detracting from the doctor patient relationship. PMID- 7794137 TI - Holistic medicine. AB - When the author completed medical school in 1981, the importance of psychoneuroimmunology, treating patients as a 'whole person', and experiencing meditation as a form of stress management, were not covered in the medical curriculum as they are now. This article gives a brief overview of these topics and presents several case histories and studies to illustrate the benefits of a holistic approach. PMID- 7794140 TI - Sexuality and the psyche. AB - A lack of knowledge of human sexuality, on completing medical school, was the prompt to explore this area more fully. However, as more experience is gained in an area, more questions are raised, emphasising that the black and white approach taken in medical school is often inappropriate in human health. PMID- 7794139 TI - Clinical hypnosis. AB - Clinical hypnosis is now an available tool for general practitioners. Hypnotists do not possess any magical powers. It is the patient who possess the magic; the hypnotist merely unlocks this power. PMID- 7794138 TI - Munchausen syndrome by proxy: a profile for medical child abuse. AB - The term Munchausen Syndrome by Proxy describes a pattern of physical abuse in which a perpetrator produces or fabricates illness in a victim. Victims are almost always children. We alternatively call this behaviour medical child abuse. Our report describes five recent cases. Two presented with infantile apnoea, one with alleged hypoventilation, one with recurrent vomiting and one with recurrent infections. Three of the perpetrators were mothers, two were fathers. In three cases diagnoses were confirmed by covert video surveillance. Contrary to popular beliefs, this behaviour is not rare and is not a syndrome of any known psychopathology. It is simply another, very dangerous, form of child abuse. Reported victim mortalities range from 9% to 31%. To ensure child safety we suggest the medical, legal and law enforcement communities begin to view this entity more as a profile of criminal abusive behaviour and less as a medical syndrome. PMID- 7794141 TI - Is that absolutely true? Reflections on reality in general practice. AB - Biomedical scientific knowledge appeared to me, as a medical student, to be carved in stone. After many years in general practice it seemed more like it was carved in the shifting sands of time. A feeling of insecurity in diagnosis and treatment followed. There was also a perceived superiority of scientific knowledge over knowledge gained by other means. This did not sit well with my experience in everyday general practice. This article explores a rational framework for change in medical science and a justification for giving equal importance to other forms of knowledge in general practice. PMID- 7794142 TI - Hospital in the home units. Early issues for GP involvement. AB - This paper reviews the early challenges for Hospital in the Home units which choose to utilise general practitioner skills. A model is described. Issues surrounding GP selection, remuneration, responsibility, leadership, and other hurdles are described. Since alternatives to GP involvement exist, GPs should be prepared to seize this important opportunity. PMID- 7794143 TI - The star of general practice. AB - These dimensions are not mutually exclusive. They all inter-relate. Their purpose is to provide a series of focal points to group the various knowledge, attitudes and skills required of a general practitioner, which can be diagrammatically represented by a five pointed star (Figure 1). The description of the domains in Table 2, is not exhaustive. It is intended to demonstrate how the knowledge, attitudes and skills of a general practitioner can be concisely described by a small number of categories. This framework is offered as a means of organising the long and detailed lists that describe what GPs do. These domains can be a vehicle for examining a GP curriculum or be used for program evaluation. They provide a description of the skills of a competent GP that can be used in many situations but also could be used to describe the skills of other professional groups, for example, teaching. This paper has presented a description of the six domains or skills required by a general practitioner. The purpose is to provide a description that is both easy to remember and yet sufficiently comprehensive to cover all the key competencies, and objective to encourage debate in this area. PMID- 7794145 TI - Treatment of menorrhagia. AB - The treatment of menorrhagia has changed significantly in two ways. Between 20% to 40% of women complaining of menorrhagia have normal to below normal blood loss and may avoid medical and surgical treatment by learning how to cope with menstrual loss. Ninety per cent of women with menorrhagia not responding to drug therapy can be treated by a wide variety of endoscopic procedures and hysterectomy is required for only a few of these patients. This article reviews the subject with emphasis on current practice and new endoscopic procedures. PMID- 7794144 TI - Review of mammography. PMID- 7794146 TI - Evaluation of an educational program in rational prescribing for GP trainees. AB - Education on rational prescribing is receiving increased emphasis but the effectiveness of this education is not well researched. This study used a randomised trial to evaluate a seminar for general practice trainees on rational prescribing of antibiotics and benzodiazepines, two important areas of general practice prescribing. Results show a decrease in prescribing of antibiotics by the group of trainees attending the seminar but no effect on an already low level of benzodiazepine prescribing. The study provides evidence that group educational approaches to influencing prescribing behaviour can be effective. PMID- 7794147 TI - Can GPs co-operate after hours in a competitive urban environment? AB - Before designing an intervention aimed at improving the quality of after-hour general practice services to the residents of a relatively isolated outer suburb of Brisbane, a survey of 247 residents was conducted to assess the provisions of after-hours care. The results of the survey were presented to the suburb's general practitioners (GPs). Meetings with the GPs led to attempts at improved communication, using patient-held Health Summary Cards and doctor-to-doctor clinical feedback forms. Forty-four per cent of the 27 GPs participated in the co operative scheme. One year later the community was resurveyed to assess the impact of the changes in medical services. There was a small but insignificant increase in satisfaction with the provision of after-hours care from 45% to 48%. PMID- 7794149 TI - Common chronic skin disorder. PMID- 7794150 TI - Andrea Mant. General practitioner researcher. PMID- 7794148 TI - Gout: 'a disease of plenty'. AB - Gout is a syndrome caused by an inflammatory response to the formation of monosodium urate monohydrate crystals which develop secondary to hyperuricaemia. Acute and chronic forms occur. Hyperuricaemia may be due to environmental and/or genetic factors. It most commonly affects middle-aged males. This article discusses the management of both acute and chronic gout. PMID- 7794152 TI - Rural general practice: is it a distinct discipline? AB - This article, an edited version of a paper presented to the RNZGP/RACGP Combined Conference, Wellington, New Zealand, 1994 explores the nature of rural practice so as to determine whether it qualifies as a distinct discipline. Certainly rural doctors live and work in a different world from their urban counterparts. The psychology and sociology of rural communities are markedly different from the cities. Also, the spectrum of illness and injuries with which rural doctors have to cope is specific to rural areas, and the structure and process of health services in the country are quite different. Rural doctors carry a higher level of clinical responsibility and provide a wider range of services in relative professional isolation. PMID- 7794153 TI - Patient education. Dry skin. PMID- 7794151 TI - Epilepsy or pseudo-epilepsy? AB - The practitioner must be sensitive to the possibility of patients' hidden agendas in presentation, particularly in cases with associated inconsistencies. Issues can be clarified by comprehensive clinical assessment and communication with other health professionals and significant others. This case illustrates some of these issues. PMID- 7794154 TI - Clinical decision making. Are computers really helpful? AB - The introduction of computers to Australian general practice will require changes beyond those of simply changing from pen to keyboard. The form in which information is stored has a major impact on how it can be used. General practitioners should be informed about this potential and take part in decision making about the use of computers. PMID- 7794156 TI - Musculoskeletal medicine tip. Slipping rib syndrome. PMID- 7794155 TI - Eye and penile problems in a young man. PMID- 7794157 TI - Practice tip. Simple removal of xanthoma. PMID- 7794158 TI - Acromioclavicular joint. PMID- 7794159 TI - Facet joint pain. PMID- 7794160 TI - Paediatric burns. PMID- 7794161 TI - Pap smear technique. PMID- 7794162 TI - Pap smear technique. PMID- 7794163 TI - Use of antibiotics when taking the oral contraceptive pill. PMID- 7794164 TI - Euthanasia and ethics. PMID- 7794166 TI - Chronic pain and 'faith healing'. PMID- 7794167 TI - Mitogenic responses of the head-associated lymphoid tissues of the chicken. AB - A blastogenesis microassay employing 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) was adapted to measure blastogenic responses of lymphocytes from the chicken's head-associated lymphoid tissues (i.e., the harderian gland and conjunctiva-associated lymphoid tissue) to T- and B-cell mitogens. Lymphocytes isolated from peripheral blood, spleen, and the harderian gland had highly significant (P < 0.01) responses to T- and B-cell mitogens compared with control lymphocytes cultured without mitogens. Cultured lymphocytes obtained from the harderian gland had highly significant mitogenic responses to the T-cell mitogen concanavalin A (25 to 100 micrograms/ml) and to the B-cell mitogen Salmonella typhimurium lipopolysaccharide (1.25 to 5.0 micrograms/ml) compared with the control lymphocytes. Mitogenic responses of cultured lymphocytes obtained from the conjunctiva-associated lymphoid tissue could not be measured within the given parameters of the blastogenesis microassay. This was primarily due to the low yield of lymphocytes, which proved to be a limiting factor. The ability of the MTT blastogenesis microassay to detect blastogenic responses of the harderian gland to mitogens may be indicative of its usefulness for measuring cell-mediated immunity responses to other antigens. PMID- 7794165 TI - Supraventricular tachycardia and eczema due to milk allergy. PMID- 7794168 TI - Induction of tibial dyschondroplasia and suppression of cell-mediated immunity in chickens by Fusarium oxysporum grown on sterile corn. AB - An isolate of Fusarium oxysporum from corn associated with Kaschin-Beck disease in humans was tested for its ability to induce tibial dyschondroplasia (TD) and toxicity in chicks. Both leghorn and broiler chicks were fed diets in which corn was replaced with varied amounts (0% to 50%) of the F. oxysporum culture grown on sterile corn, or with known TD-inducing agents. F. oxysporum did not affect body weight in either type of chicks. In leghorn chicks, neither F. oxysporum nor the known TD-inducing agents (F. equiseti, 4%; tetramethylthiuram disulfide [Thiram], 35 ppm) caused TD. However, F. oxysporum at high levels (50%) and the two known TD-inducing agents reduced interdigital cutaneous response to phytohemagglutinin P challenge. In addition, Thiram also reduced body-weight gain by more than 17%. In female broiler chicks (Cornish Rock), F. oxysporum not only decreased cell mediated cutaneous response to phytohemagglutinin-P but also increased TD incidence; these same effects were observed with F. equiseti and Thiram. Histological examinations revealed similar pathological changes among dyschondroplastic lesions induced by F. oxysporum, F. equiseti, and Thiram. Results of this experiment indicate that the isolate of F. oxysporum from the region in which Kaschin-Beck disease is endemic can induce TD in broiler chicks and that it is immunosuppressive. PMID- 7794169 TI - Physiologic and electrocardiographic changes occurring in broilers reared at simulated high altitude. AB - An experiment was conducted to determine whether differences in the electrocardiograms (EKGs) of broilers reared at simulated high altitude from the day of hatch can be used to predict which birds are developing ascites. In three replicate experiments, conducted with 100 broilers per replicate, birds were reared at a simulated altitude of 3000 meters or at ambient atmospheric pressure. Lead I, II, and III EKGs were obtained from all birds on days 0, 14, 28, and 42. No consistent significant differences were seen on day 0 in the amplitude of the R or S wave or total amplitude of the QRS complex when broilers that developed ascites while being reared at simulated high altitude were compared with unaffected birds reared at simulated high altitude and with birds reared at ambient atmospheric pressure. On days 14 and 28, the average amplitude of the S wave and the total amplitude of the QRS complex were significantly higher in the ascites group than in the two other groups. Packed cell volumes were significantly higher in birds reared at simulated high altitude at all sampling days (days 14, 28, and 42) than in those reared at ambient atmospheric pressure, and they were significantly higher in the ascites group on day 28 than in the two other groups. Birds in the ascites group weighed significantly less than the two other groups by day 14, and this trend persisted. PMID- 7794171 TI - Escherichia coli cellulitis: experimental infections in broiler chickens. AB - The objectives of this study were to evaluate the role of trauma to the skin in development of Escherichia coli cellulitis and to compare the abilities of three cellulitis isolates (O78, O115, O21,83), one airsacculitis isolate (untypable) and one fecal isolate (O86) of E. coli to induce cellulitis in broiler chickens. Forty-eight 4-week-old commercial broiler chickens were housed in groups of six in eight battery cages. For five groups, the skin on the left side of the abdominal region of chickens was traumatized by scratching with a 22-gauge needle, then contaminated with a swab dipped in a broth culture of one of the five E. coli isolates. For chickens in the remaining three groups, an avian cellulitis culture (O115, O21,83) or sterile broth was applied to intact skin. The experiment was duplicated. All birds were euthanatized 10-13 days postinoculation. No lesion developed in chickens in which the skin had not been traumatized. Among the traumatized birds, cellulitis isolates induced characteristic lesions of cellulitis in 86% of the birds, whereas airsacculitis and fecal isolates induced lesions in 42% and 8% of birds, respectively. Severe or moderate gross pathologic changes were found in 86% and microscopic pathologic changes were found in 88% of birds inoculated with cellulitis isolates; the corresponding percentages for the airsacculitis isolate were 25% and 17%. This study demonstrated that trauma to the skin is necessary for initiating disease and that strains of E. coli of serotypes epidemiologically associated with cellulitis are highly virulent in experimental infection. PMID- 7794170 TI - Characteristics of Escherichia coli isolates from avian cellulitis. AB - The purpose of this study was to characterize Escherichia coli isolates from avian cellulitis, particularly with respect to the occurrence of potential virulence factors. At slaughter, five broilers with lesions of cellulitis were selected from each of 20 farms from among the broilers processed. One hundred E. coli isolates from the lesions were characterized with respect to serotype; biotype; drug susceptibility; plasmid profile; ability to produce aerobactin, colicin, colicin V, and hemolysin; and cytotoxicity for Vero cells and chicken fibroblasts. The same properties were determined from a collection of 25 E. coli from the feces of chickens. Serotyping showed that, among the cellulitis isolates, 23 belonged to O group 78, 14 belonged to O2, eight belonged to O115, and seven belonged to O(21.83); 25 were untypable. Isolates from a single farm typically belonged to three to five O groups. More than half of the fecal isolates were untypable, and the rest were distributed among seven O groups. Biotype, drug-resistance pattern, and plasmid profile could not be used as markers of avian cellulitis E. coli. No plasmid was detected in 12% of cellulitis isolates and 48% of fecal isolates. No isolate was hemolytic or showed cytotoxic effects. Aerobactin was produced by 90% of cellulitis isolates, and colicin was produced by 85% of these isolates; the corresponding percentages for the fecal isolates were 16% and 40%. Production of colicin V was detected in 21% of cellulitis isolates and 24% of fecal isolates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794173 TI - Consumptive coagulopathy in turkeys exposed to Pasteurella multocida. AB - When turkeys were inoculated intramuscularly with live Pasteurella multocida, three of the four inoculated turkeys developed an increase in modified Russell's viper venom time (mRVVT) 24 hours after inoculation. This increase was followed by irregular decreases and increases in mRVVT at subsequent bleedings. When turkeys were inoculated intravenously with P. multocida, the mRVVT increased markedly after inoculation in all eight inoculated turkeys: 9 hours later, the average mRVVT was significantly (P < 0.05) higher than that of the uninoculated turkeys. No microthrombi were observed in the blood vessels of the liver, spleen, kidneys, or lungs. An increase in mRVVT was interpreted as an excessive consumption of one or more of clotting factors X, V, II, and I. These results indicate that consumptive coagulopathy could be a factor in the pathogenesis of fowl cholera in turkeys. PMID- 7794174 TI - Incidence of Pasteurella multocida in poultry house cats used for rodent control programs. AB - Cats used as mousers in commercial poultry breeder farms were tested for the presence of Pasteurella multocida. Of the cats tested, 72.7% were positive for P. multocida serotypes common to both farm cats and commercial broiler breeders. Thirty-one percent were type 1, 19% were type 4, and 6% were type 3.4. PMID- 7794172 TI - Immunosuppression and intracellular calcium signaling in splenocytes from chicks infected with chicken anemia virus, CL-1 isolate. AB - Hematocrits, histopathology, concanavalin A-induced lymphocyte proliferation, intracellular calcium signaling, and lymphocyte subpopulations were analyzed over a 6-week period in individual chicks inoculated with the CL-1 isolate of chicken anemia virus. Lymphoid depletion/atrophy was present in the thymus and bone marrow by 11 days post-infection (PI). Anemia was present at 14 days PI. The mean lymphocyte proliferation stimulation index (SI) of the inoculated group was significantly lower than that of the control group at 11 days PI. This response was reversed at 18 days PI, when the SI of the inoculated group was significantly higher than that of the controls; values subsequently returned to baseline. The increase in intracellular calcium levels in CAV-infected chicks and controls paralleled the proliferative response. Percentages of CD3-, CD4-, CD8-, and natural-killer-positive-staining cells decreased significantly at 18 and 25 days PI. The most dramatic decrease occurred in the CD8-positive-staining cell population at 18 and 25 days PI. PMID- 7794175 TI - Incidence of campylobacters in the intestine of avian species in Alabama. AB - Avian species necropsied at the C. S. Roberts Veterinary Diagnostic Laboratory, Auburn, Alabama, from December 1993 until May 1994 were examined for the incidence of intestinal campylobacters. Ninety-one intestinal swabs, representing 66 separate cases and 17 different avian species, were collected and placed into Cary-Blair transport medium. Selective enrichment and culture media were used for initial isolation of Campylobacter spp. Presumptive colonies were identified as Campylobacter spp. by phase-contrast microscopy and Gram stain, and they were confirmed by serological latex agglutination. Campylobacter spp. were isolated in 18 (19.7%) of the 66 cases. From the remainder of the cases, 13 (15%) yielded presumptive colonies on Campy-Cefex agar; however, they were not confirmed serologically as Campylobacter spp. Use of Cary-Blair transport medium held in refrigeration for up to 24 days did not hinder the determination of campylobacters in intestinal samples. A variety of avian species, including chicken, emu, hawk, ostrich, and parrot, harbored commensal campylobacters and therefore should be considered potential reservoirs. PMID- 7794176 TI - Formaldehyde vaporization in the hatcher and the effect on tracheal epithelium of the chick. AB - Chicken embryos were exposed to formaldehyde vapors in the hatcher during the final 3 days of incubation. Measured formaldehyde levels approached 130 ppm. Tracheas collected at hatch and 5 days post-hatch were evaluated for functional and morphologic changes. Tracheal cilia motility was reduced in formaldehyde exposed chicks. Scanning electron microscopy revealed blunted cilia and blebs occurring in the cilia surfaces. At 5 days of age, excessive tracheal mucus was present. Sloughing of the tracheal epithelium was visible by light microscopy. PMID- 7794177 TI - Salt toxicosis in commercial turkeys. AB - Salt toxicosis was confirmed in a flock of 20,000 thirteen-week-old tom turkeys experiencing an increase in mortality. Clinical signs included polydipsia, diarrhea, ataxia, incoordination, tremors that progressed to depression, sternal and lateral recumbency accompanied by torticollis, and death. Mortality over a 5 day period was 6.7%. Necropsy lesions included pallor and dehydration of pectoral muscles, hepatic congestion, and fluid-filled small and large intestines. Microscopic lesions consisted of bilaterally symmetrical areas of necrosis within the cerebral hemispheres accompanied by vascular congestion and edema, as well as hyalinization of the glomerular capillary walls of the kidney and eosinophilic granular casts in the renal tubules. Average salt concentration in the feed from affected houses with 8.04%. PMID- 7794178 TI - Hypoglycemia, enteritis, and spiking mortality in Georgia broiler chickens: experimental reproduction in broiler breeder chicks. AB - The clinical signs, hypoglycemia, and mortality of "spiking mortality syndrome" were experimentally reproduced. Seven groups of day-old male primary broiler breeder chicks were orally inoculated with tissue and/or fecal-urate homogenates taken from field broilers with spiking mortality syndrome and from field broilers with enteritis and/or runting-stunting syndrome. All homogenates used as inocula were shown by transmission electron microscopy and negative staining to contain arenavirus-like particles. Inocula produced from field broilers with spiking mortality syndrome contained the highest numbers of the arena-virus-like particles and produced the highest percentage of hypoglycemic chicks 13-15 days postinoculation after a 5-to-9-hour fast. These homogenates also produced the most significant differences in mean plasma growth hormone and insulin-like growth factor-1 levels. The significance of the arenavirus-like particles is unknown but is currently being investigated. PMID- 7794179 TI - Intralesional herpesvirus, reovirus-like particles, and bacteria in a flock of broiler chicks with spiking mortality, diarrhea, and enterotyphlitis. AB - The search for a solitary cause of spiking mortality (so-called spiking mortality syndrome) among broiler chicks has been thwarted by the fact that multiple agents cause similar mortality histograms. In the present case report, we describe intralesional herpesvirus, reovirus-like virus particles, and bacteria in small and large intestines from chicks with a spiking mortality histogram, diarrhea, and enterotyphlitis. We attributed the spiking mortality histogram to starvation coupled with diarrhea. PMID- 7794180 TI - Effect of calcium/phosphorus imbalance in the ration on flock performance in two broiler flocks in north Georgia. AB - Five- and six-day-old broilers from two flocks experiencing excessive mortality were submitted for necropsy. Rickets was diagnosed based on clinical signs of lameness and on gross and histopathologic lesions. Because of a confirmed feed mill error, these flocks had been fed a starter ration with a high calcium/phosphorus ratio (either 7.7:1 or 3.5:1). After debate concerning the profitability of salvaging the remaining birds in the affected flocks, the starter feed was replaced at 7 days of age. At processing, the affected flocks had weighted averages of body weight and feed conversion of 1.71 kg and 1.88, respectively; these averages compared favorably with the company averages of 1.72 kg and 1.87. The majority of the mortality in the affected flocks occurred during the first week. This case report demonstrates that it may be advantageous for a producer to salvage chicks that have been affected severely with rickets at less than 1 week of age. PMID- 7794181 TI - Enteritis in turkeys associated with an unusual flagellated protozoan (Cochlosoma anatis). AB - Outbreaks of enteritis associated with an unusual flagellated protozoan occurred in six California turkey flocks during the summer of 1992. Certain morphological and ultrastructural details of the parasite, which resembles Cochlosoma anatis, are illustrated with scanning and transmission electron micrographs. The flagellate attached to the intestinal mucosa by means of a sucker-like apparatus, and circular impressions of the sucker were created on the surface epithelium. Histological lesions were characterized by blunting and fusion of villi; cellular infiltration of the lamina propria with lymphocytes, plasma cells, histiocytes, and heterophils; and increased numbers of mitotic figures in crypt epithelium. PMID- 7794182 TI - Erysipelas in quail and suspected erysipeloid in processing plant employees. AB - Erysipelas was diagnosed in two commercial breeder flocks of Coturnix quail and was characterized clinically by sudden mortality. At necropsy, lesions comprised generalized congestion, hemorrhages in the thigh and breast muscles, swelling of liver, spleen, and kidney, and dark red edematous lungs. Erysipelothrix rhusiopathiae was cultured from visceral organs of affected birds. Medication with penicillin in the drinking water controlled the mortality. A possible source of infection was fish raised on the premises. Seven people at the quail processing plant developed localized inflammation of the fingers, which responded when antibiotic therapy for erysipeloid was initiated. PMID- 7794183 TI - Mycotic rhinitis in an ostrich. AB - A 2-year-old female ostrich had become gradually emaciated over a 4-month period and subsequently died. Gross necropsy revealed a granulomatous mass filling the right nasal passageways. Microscopically, the mass contained numerous thin, regular-diameter, septate, branching fungal hyphae consistent with Aspergillus sp. and foreign plant material. This appears to be the first report of a mycotic granuloma limited to the nasal cavities of an ostrich or any other ratite species. PMID- 7794184 TI - Intestinal smooth muscle hyperplasia in a rhea (Rhea americana). AB - Smooth muscle hyperplasia of the small intestine occurred in an 18-month-old rhea (Rhea americana). The mucosal thickening was 2-3 mm, and the enlarged muscle layers averaged 5 mm thick. The intestinal villi were lengthened, pleated, and expanded by smooth muscle hyperplasia within the lamina propria. The prominent muscularis mucosa averaged 20 smooth muscle cells thick. The tunica muscularis had symmetrical hyperplasia of both the inner circular muscle layer, which had an excess of 220 cells, and the outer longitudinal muscle layer, which consisted of five to six large fascicles, each approximately 75 cells thick. The smooth muscle hyperplasia, without hypertrophy, in all intestinal muscle layers differs greatly from mammalian cases of smooth muscle hypertrophy, in which the increase in intestinal size results from smooth muscle hypertrophy of the tunica muscularis. PMID- 7794186 TI - Comparison of prophylactic and therapeutic efficacy of Salmonella enteritidis immune lymphokines against Salmonella enteritidis organ invasion in neonatal Leghorn chicks. AB - Investigations in our laboratories have indicated that when Salmonella enteritidis (SE)-immune lymphokines--supernatants from concanavalin-A-stimulated T cells derived from SE-immune adult chickens--were administered intraperitoneally to 1-day-old chicks before SE challenge, they conferred protection against SE organ invasion within 24 hr. This resistance mediated by SE immune lymphokines was associated with a concomitant increase in peripheral blood polymorphonuclear leukocytes that peaked 4 hr after SE challenge. In the present study, we evaluated efficacy of SE-immune lymphokines in protecting chicks against SE organ invasion and alterations in peripheral blood polymorphonuclear leukocyte counts. Administration of SE-immune lymphokines to chicks either 30 min or 6 days before SE challenge caused a significant reduction in SE organ invasion. However, when SE-immune lymphokines were administered 2 days after SE challenge, there was no reduction in SE organ invasion. Both prophylactic (before SE challenge) and therapeutic (after SE challenge) administration of SE-immune lymphokines caused a significant increase in numbers of peripheral blood polymorphonuclear leukocytes. Results from these studies suggest that SE-immune lymphokines have potential value as an effective prophylactic but not as a therapeutic modulator of early resistance to SE organ invasion in neonatal leghorn chicks. PMID- 7794187 TI - Detection of specific antibodies directed against a consistently expressed surface antigen of Mycoplasma gallisepticum using a monoclonal blocking enzyme linked immunosorbent assay. AB - Sera from 14 groups of chickens inoculated with different laboratory and field strains of Mycoplasma gallisepticum (MG) were used to compare the diagnostic potential of the hemagglutination-inhibition (HI) test and a recently developed monoclonal blocking enzyme-linked immunosorbent assay (ELISA). HI was performed with strain A5969, commonly used as hemagglutinating antigen, and it could detect 62.7% of the inoculated chickens as positive. Of all sera, 83% proved to be positive when examined with the blocking ELISA. The difference between the sensitivities of the two methods was due to group-specific insensitivity of the HI test. None of the sera from groups inoculated with strains K 1501, K 1503, K 503, or K 703 and only half of the sera from groups inoculated with K 1453 or 236C could inhibit the activity of the A5969 hemagglutinating antigen, indicating antigenic differences between these challenge strains and the diagnostic strain. ELISA detected MG-specific antibodies in every group of sera, although inoculation with variant strains K 503 or K 703 resulted in lower level of antibody production than inoculation with other strains. The monoclonal blocking ELISA can be useful in the serological diagnosis of MG infections, because it is based on a consistently expressed, specific region of MG. PMID- 7794185 TI - Central nervous system toxoplasmosis in Roller canaries. AB - Several birds in a flock of 40 Roller canaries (Serinus canaria) from an outdoor aviary in Victoria, Australia, developed central nervous system signs that included blindness, nystagmus, ataxia, and head rotation. Four died, and four were euthanatized. Two euthanatized birds were submitted for microscopic examination of tissues. Brain lesions in both birds consisted of scattered foci of nonsuppurative meningoencephalitis with gliosis, mild to moderately extensive lymphocytic/plasmacytic perivascular cuffs, and a patchy increased prominence of cerebral blood vessels associated with hypertrophy of the vascular endothelium and/or thickening of their connective tissue walls. These lesions were associated with the presence of Toxoplasma gondii tissue cysts. Lesions in the eyes of both birds were bilateral and consisted of severe plasmacytic/granulomatous ophthalmitis. Surviving birds were treated with trimethoprim and sulfadiazine, no subsequent deaths occurred, and no new cases developed over an 8-month period. PMID- 7794190 TI - Isolation of Salmonella from poultry tissue and environmental samples: a nationwide survey. AB - A nationwide survey of veterinary laboratories culturing poultry tissue and environmental samples for Salmonella found a large variation in isolation procedures. There were 17 different selective enrichment media or combinations of enrichment media being used for poultry tissue samples. Variations were found in how long the selective enrichments were incubated and in the temperature of incubation. There were 14 different plating media being used. Many laboratories screen and identify only one colony from the plating media. For the protection of poultry breeding and hatchery organizations and with the formation of official poultry monitoring programs, with their legal and public health implications, it becomes increasingly important that diagnostic laboratories adopt minimal standardized protocols for isolating Salmonella. PMID- 7794189 TI - Prevalence of Salmonella in broiler flocks: effect of litter water activity, house construction, and watering devices. AB - Litter samples from 24 flocks of broilers and four flocks of broiler breeders were evaluated for Salmonella contamination, water activity (Aw), and total moisture content (MC). The drag swab (DS) monitoring system was used to collect samples to detect Salmonella contamination. Simultaneously, representative samples of the uppermost surfaces of dry (loose) litter and wet (caked) litter were collected for Aw and MC analyses. On dry litter surfaces, high Aw values (0.90-0.95) were associated with flocks Salmonella-positive using DS; low Aw values (0.79-0.84) were associated with flocks Salmonella-negative by DS; and transition Aw values (0.85-0.89) were associated with flocks having an increased risk for the presence of Salmonella. The association of high Aw values with Salmonella risk was not observed for wet (caked) litter surfaces. Observations suggest that limiting Aw in the litter base of broiler houses may create a less favorable environment for the multiplication of Salmonella and thus a more hygienic environment for broiler production. PMID- 7794188 TI - Effects on turkey poults of feeding Fusarium moniliforme M-1325 culture material grown under different environmental conditions. AB - The effects of feeding Fusarium moniliforme M-1325 culture material (CM), grown under different environmental conditions, were studied in turkey poults. Poults were fed a control diet or diets containing four levels of FB1 (75, 150, 225, or 300 mg/kg) prepared from F. moniliforme M-1325 cultures that produced 7800 (CM1) or 4000 mg FB1/kg (CM2). F. moniliforme M-1325 CM that produced a low concentration of FB1 (350 mg FB1/kg) was also used to prepare an additional diet containing 75 mg FB1/kg (CM3). Dose-dependent decreases in feed intake and body weight gains and dose-dependent increases in liver weights and serum sphinganine (SA) to sphingosine (SO) ratios were observed in poults fed CM1 or CM2. Poults fed CM3 consumed more feed and had lower body-weight gains than controls or poults fed CM1 or CM2 (at 75 mg FB1/kg). Poults fed CM3 also had increased liver weights and SA:SO ratios compared with control poults. Generalized hepatocellular hyperplasia was observed in all FB1 treatment groups. Biliary hyperplasia was evident in turkeys fed 150 to 300 mg FB1/kg. Results indicate that at equivalent dietary FB1 levels, F. moniliforme cultures producing different concentrations of FB1 differ in their effects on turkey poults. PMID- 7794191 TI - Microbiological analysis of the early Salmonella enteritidis infection in molted and unmolted hens. AB - A study was conducted in which the early kinetics (4 hr to 96 hr) of an infection by Salmonella enteritidis in older white leghorn hens was examined, and a molt was induced through withholding feed to determine its effect on the progression of this infection. Molted and unmolted hens were orally infected with 5-10 x 10(6) S. enteritidis on day 4 of the feed removal. At 4, 24, 48, 72, and 96 hr postinfection, liver, spleen, ileum, colon, cecum, and feces were removed from six hens per group and sampled for the presence of the challenge organism. By 24 hr postinfection, S. enteritidis was most prevalent in the cecum and feces of unmolted hens, and this prevalence continued throughout the experimental period. In molted hens, however, S. enteritidis could be detected in a high percentage (90-100%) of colon, cecum, and feces samples at 24 to 96 hr postinfection and in 67% or more of ileum samples at 48 to 96 hr postinfection, indicating a much wider distribution of the S. enteritidis along the intestinal tract than in unmolted hens. The numbers of S. enteritidis recovered from these alimentary samples were also significantly higher in molted than unmolted hens. S. enteritidis could not be detected in livers or spleens of either treatment group at 4 or 24 hr postinfection. At 48, 72, and 96 hr postinfection, 50% or more of the livers and spleens in both the molted and unmolted hens were positive for the challenge organism, but significantly more S. enteritidis was recovered from the organs of the molted hens at these three sampling times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794192 TI - Presence of avian influenza virus (AIV) subtypes H5N2 and H7N1 in emus (Dromaius novaehollandiae) and rheas (Rhea americana): virus isolation and serologic findings. AB - Avian influenza virus (AIV) subtypes H5N2 and H7N1 were isolated from emus (Dromaius novaehollandiae) and rheas (Rhea americana) in Texas and North Carolina. All the rheas and emus had a history of respiratory disease except one emu, which was clinically normal. The isolates were not pathogenic for chickens and turkeys under the conditions of the experiment. Humoral antibodies to all known hemagglutinin (H) subtypes except H10, H13, and H14 and to all nine neuraminidase (N) subtypes were found in emus and rheas in 11 states. Therefore, emus and rheas are susceptible to infection with several AIV subtypes. PMID- 7794193 TI - Effect of T-lymphocyte depletion on the pathogenesis of marble spleen disease virus infection in ring-necked pheasants. AB - The purpose of this study was to determine the effect of cyclosporine (CSP) mediated T-lymphocyte depletion on the pathogenesis of marble spleen disease virus (MSDV) infection in ring-necked pheasants. Seventy-two 6-week-old pheasants were divided into three groups; one group of 18 birds was inoculated with MSDV, a second group of 18 birds was treated with CSP, and a third group of 36 birds was both treated with CSP and inoculated with MSDV. Two birds each from both of the smaller groups and four birds from the largest study group were necropsied periodically over a 14-day period. T-lymphoblastogenesis assays documented significant T-cell depression in the CSP-treated groups. Routine histology and immunohistochemical staining for MSDV antigen demonstrated that the CSP-treated MSDV-inoculated birds had higher lesion incidence, had wider tissue distribution of virus, and retained virus in tissues longer than did the MSDV-inoculated-only birds. These results indicate that T-lymphocytes play a role in the host response to infection with MSDV. PMID- 7794194 TI - Comparative pathology of intravenously inoculated wild duck- and turkey-origin type A influenza viruses in chickens. AB - Five-week-old specific-pathogen-free chickens were inoculated intravenously with one of 16 low-pathogenicity type A influenza virus isolates; 14 were of wild duck origin, and two were of turkey origin. Tubulointerstitial nephritis was the most frequent specific histopathologic change. The frequency and severity of kidney lesions were independent of the virus hemagglutinin-neuraminidase subtype or titer of the challenge virus. Influenza nucleoprotein was most frequently demonstrated in the kidney and was consistently localized to necrotic proximal and/or distal renal tubule epithelium. Common nonspecific histopathologic changes were lymphoid hyperplasia of the spleen and cecal tonsils, as well as lymphocyte depletion in the cloacal bursa. Uncommon histopathologic changes, in decreasing order of frequency, were interstitial pneumonia, lymphoid follicular hyperplasia in the myocardium, and lymphocytic tracheitis. Histopathologic changes were rare or absent in the jejunum, duodenum, pancreas, and brain. The low-pathogenicity avian-origin type A influenza virus isolates were epitheliotropic in chickens, primarily nephrotropic. Such findings were dissimilar from findings with highly pathogenic avian-origin type A influenza virus isolates both in severity and in tissue distribution of histopathologic changes and influenza viral antigen. PMID- 7794195 TI - An enzyme-linked immunosorbent assay for detection of avian mycoplasmas in culture. AB - An antigen-capture enzyme-linked immunosorbent assay (ELISA), using monoclonal antibody (Myc-9) against Mycoplasma pneumoniae, was developed for the detection of M. gallisepticum, M. synoviae, M. meleagridis, M. iowae, M. anatis, M. iners, and M. gallinarum antigens in cultures. ELISA plates were coated with Myc-9 and reacted with the different avian mycoplasma antigens, which were detected with adsorbed polyclonal anti-mycoplasma serum followed by anti-rabbit enzyme-labeled conjugate antiserum. Nonspecific reactions and cross-reactivity were eliminated by adsorbing polyclonal antisera with a pool of heterologous antigens, and a high degree of sensitivity was obtained by both antigen enrichment and treatment with the detergent N-octyl glucoside. Under these conditions, the test detected less than 10 colony-forming units/ml. This antigen-capture ELISA appears to be a highly specific, sensitive, reproducible tool and efficient in the diagnosis of mycoplasma infection. PMID- 7794196 TI - Association between pathogenicity of infectious bursal disease virus and viral antigen distribution detected by immunohistochemistry. AB - Highly pathogenic infectious bursal disease virus (IBDV) strains (Ehime/91, DV86) and a moderately pathogenic strain (J1) were compared in order to clarify the association between the pathogenicity of IBDV and viral antigen distribution. Virus target cells in the bursa, thymus, spleen, and bone marrow were examined by transmission electron microscopy. Although all strains caused similar bursal atrophy, the highly pathogenic strains brought about a greater decrease in the thymic weight index and more severe lesions in the cecal tonsil, thymus, spleen, and bone marrow. Immunohistochemical detection of IBDV antigen in tissues from chickens infected with Ehime/91 and DV86 strains showed a higher frequency of antigen-positive cells in the spleen and bone marrow. Transmission electron microscopy indicated the presence of viral particles in the cytoplasm of epithelial reticular cells in the thymus and monocytes in the bone marrow. The results show that pathogenicity of field strains of IBDV correlates with lesion production in non-bursal lymphopoietic organs. The results also suggest that pathogenicity of IBDV may be associated with virus antigen distribution in non bursal lymphopoietic organs. PMID- 7794197 TI - Serotypes and DNA fingerprint profiles of Pasteurella multocida isolated from raptors. AB - Pasteurella multocida isolates from 21 raptors were examined by DNA fingerprint profile and serotyping methods. Isolates were obtained from noncaptive birds of prey found in 11 states from November 28, 1979, through February 10, 1993. Nine isolates were from bald eagles, and the remaining isolates were from hawks, falcons, and owls. Seven isolates were members of capsule group A, and 14 were nonencapsulated. One isolate was identified as somatic type 3, and another was type 3,4,7; both had unique HhaI DNA fingerprint profiles. Nineteen isolates expressed somatic type 1 antigen; HhaI profiles of all type 1 isolates were identical to each other and to the HhaI profile of the reference somatic type 1, strain X-73. The 19 type 1 isolates were differentiated by sequential digestion of DNA with HpaII; four HpaII fingerprint profiles were obtained. The HpaII profile of one isolate was identical to the HpaII profile of strain X-73. Incidence of P. multocida somatic type 1 in raptors suggests that this type may be prevalent in other wildlife or wildlife environments. PMID- 7794198 TI - Mental health law: institutionalised discrimination. AB - The aim of the paper is to propose that special mental health laws be replaced by generic protection and prevention legislation. The arguments used for the detention and compulsory treatment of persons with mental illnesses are analysed, and found not to justify protection and prevention rules which apply only to persons with mental illnesses. Two separate systems of legal intervention should be established to deal with (1) all persons in need of compulsory care and (2) all persons who require to be detained for the prevention of harm to others. PMID- 7794199 TI - Mental health law: an idea whose time has passed. AB - In this paper I argue that specific mental health law should not exist and should be replaced by modern guardianship law which is non-discriminatory and which intervenes according to need rather than diagnostic classification. Substituted consent provided by a guardian protects the patient and the treatment provider. Custody to prevent danger to others should remain with courts rather than informal proceedings where individual rights to freedom are less carefully protected. Special mental health law stigmatises people with mental illness and degrades their treatment. It also diminishes the standing of the psychiatric profession which advocates the continuation of such laws. PMID- 7794201 TI - Images of psychiatry in recent Australian and New Zealand fiction. AB - Psychiatry is variously portrayed in Australian and New Zealand fiction. This paper describes mental health professionals, settings, conditions, treatments, and social themes essayed in 128 works by 103 authors, published between 1957 and 1992. The predominant images are negative or markedly ambivalent: possible reasons for this are discussed. The perception of psychiatry by the culture in which it is formed and located, as mediated by its creative artists, has important implications for psychiatrists' understanding and explication of their social role, and has an impact on patients' expectations and experiences of psychiatry. PMID- 7794200 TI - Abnormal illness behaviour: a 25th anniversary review. PMID- 7794202 TI - A review of dissociation and dissociative disorders. AB - There has been an explosion of activity concerning dissociation and dissociative disorders overseas, but little interest is apparent in Australian psychiatric publications. This article aims to critically examine the current conceptualisation of dissociation and its proposed relevance to the understanding of psychopathology, in order to create discussion about these issues in Australian psychiatry. Multiple personality disorder and post-traumatic stress disorder are critically examined. PMID- 7794203 TI - To see or not to see: the debate over pornography and its relationship to sexual aggression. AB - The role played by pornography in the generation of thoughts, feelings, impulses and behaviours in its viewers has long been a topic of debate and controversy. The uncertainty about its potential effects on human behaviour, especially its relationship to sexual aggression, has stimulated the recent debate with the possibility of tighter censorship laws being implemented throughout this country. A review of the topic from a number of different perspectives fails to establish that pornography in its purely erotic form has any significant detrimental effect on human behaviour. More difficult to determine are its effects on psychological development. If behavioural disturbances do occur following exposure to such material, they occur in the context of an individual who shows more global disturbances of personality. The current debate regarding pornography provides an opportunity to address in a broader social context issues perhaps more significant for our society: the relationships between men and women, and the roles and recognition provided to each of the sexes. PMID- 7794204 TI - The influence of illness duration on syndrome clarity and stability in functional psychosis: does the diagnosis emerge and stabilise with time? AB - This review aims to examine the relationship between phase and duration of illness and the clarity and stability of syndromes in psychotic illness. Originating from clinical experience with first episode psychosis, where Neo Kraepelinian templates and the underlying model have felt especially awkward and ill-fitting, a hypothesis that the clinical picture of functional psychosis might become clearer over time and stabilise in individual patients is proposed which involves the notion of differentiation. A broad range of psychopathological studies and historical papers which refer directly or indirectly to the evolution of the clinical picture in psychosis over time are reviewed. The findings are difficult to interpret, since few studies have focused directly on the issue; however there is evidence of evolution over time of the clinical picture, particularly within the schizophrenia spectrum, and instability beyond this. Further research is needed to clarify the longitudinal patterns of psychopathology in psychotic illness. The capacity for evolution and instability and consequent scope for reclassification of patients has important implications for research and psychoeducation in early psychosis. PMID- 7794206 TI - The reactivation of post-traumatic stress disorder in later life. AB - Forty-five World War II veterans reporting recent reactivation of chronic post traumatic stress disorder (PTSD) symptoms were clinically assessed in order to determine war pension disability. In the course of these examinations, factors implicated in the exacerbation of their re-experiencing and arousal symptoms were recorded. The most prominent of these factors was that of physical ill health. Retirement, loneliness, comorbid psychiatric illness, anniversaries, service reunions, and alcohol and psychotropic medication usage were other factors. The natural history of chronic PTSD was observed by reviewing the veterans' medical records, which had been commenced at enlistment, prior to active service. The masking of intrusive symptoms in mid-life was usual. A terminal phase of symptomatic reactivation in older age may occur. The indelibility of the memory of fear is demonstrated by these veterans. The reticence to retell the trauma story remains a major obstacle in the study of the mental health sequelae of warfare. War-related psychiatric disorder in the elderly male is easily missed. Direct questioning regarding military service is advisable. The ineffectiveness of the management strategies offered to World War II PTSD sufferers is clearly apparent. PMID- 7794205 TI - High prevalence of thyroid function test abnormalities in chronic schizophrenia. AB - The thyroid status of 249 patients with chronic schizophrenia (males = 136, females = 113) with a median age of 36 years (range: 16 to 58 years) and a median duration of hospitalisation of 10 years (range: 1 to 30 years) was assessed. Thyroid antibodies (TAb) were found in 51 patients (20%). In female patients, 32 (28%) were TAb positive compared to 13% (n = 152, p = 0.01) in healthy female blood donors. In male patients, the prevalence of TAb was 14% compared to 7% (n = 449, p = 0.01) in healthy male blood donors. Of the 183 patients who had thyroid hormone measurements, 60% had normal test, 5% had elevated TSH and 17% had low TSH. The T4, FT41 and FT31 were significantly lower in those with low or high TSH (p < 0.001) compared to those with normal TSH. Of the 143 patients with normal TSH, 33 (23%) had low T3. In conclusion, there is a spectrum of thyroid function test abnormalities in chronic schizophrenia; this may be related to an abnormality in the central regulation of the hypothalamo-pituitary thyroid axis as well as at the peripheral level. However the association between chronic schizophrenia and the presence of thyroid antibodies, and the clinical relevance of these biochemical abnormalities, are still not clear. PMID- 7794207 TI - Childhood depression, stressors and parental depression. AB - The relationship between depression and stressors and the relationship between depression in children and depression in their parents were investigated. Depressed children aged 7-11 years (n = 20) were compared with clinical non depressed children (n = 88) and normal children (n = 55). Children, mothers and fathers in the three groups were tested. Measures included the Children's Depression Inventory, Recent Life Events Scale, Stressor Scale and Beck Depression Inventory. The findings showed that children and mothers in the depressed group reported more stressors than other children and other mothers while fathers of children in the depressed group did not report more stressors. The findings also showed that mothers of depressed children were more depressed than mothers of normal children while there were no differences between the scores of fathers in the three groups. PMID- 7794208 TI - Depression in patients with HIV and AIDS. AB - In this paper we review studies of depression in patients with HIV/AIDS. Methodological issues of importance in understanding and evaluating depression in this patient population are described, and methodological variations between studies, particularly in reference to methods of case detection, diagnostic criteria used and characteristics of the populations studied, are identified. The findings reported in the current literature in general are contrary to what would be expected from an examination of the significant biological and psychosocial stresses of individuals with HIV, and are inconsistent with those of other life threatening illnesses and CNS diseases. Clear conclusions regarding the prevalence of depression and its effect in patients with HIV/AIDS cannot yet be made. PMID- 7794209 TI - Neural networks and psychiatry: candidate applications in clinical decision making. AB - Neural networks comprise a fundamentally new type of computer system inspired by the functioning of neurons in the brain. Such networks are good at solving problems that involve pattern recognition and categorisation. An important difference between a neural network and a traditional computer system is that in developing an application, a neural network is not programmed; instead, it is trained to solve a particular type of problem. This ability to learn to solve a problem makes neural networks adaptable to solving a wide variety of problems, some of which have proved intractable using a traditional computing approach. Neural networks are particularly suited to tasks involving the categorisation of patterns of information, such as is required in diagnosis and clinical decision making. In the last three years reports of applications involving neural networks have begun to appear in the medical literature, and these are described in this paper. However, a comprehensive search of the literature has shown that there have not as yet been reports of any applications in psychiatry. This paper discusses the nature of clinical decision making, outlines the sorts of problems in psychiatry which neural networks applications might be developed to address, and gives examples of candidate applications in clinical decision making. PMID- 7794210 TI - Intensive cognitive-behaviour group therapy for diagnostically heterogeneous groups of patients with psychiatric disorder. AB - This uncontrolled study evaluates the efficacy of a combined treatment of medications (for the majority of patients) and a closed group, intensive (two week) cognitive-behaviour therapy programme for heterogeneous groups of psychiatric patients. Five hundred and thirty-one patients at a private psychiatric clinic were included in the study. Self-report measures of depression, anxiety, self-esteem and "locus of control" were administered before and after treatment and at intervals up to one year later. Statistically and clinically significant improvements were found in all measures and these improvements were maintained up to one year. The results provide support for the efficacy of the treatment. PMID- 7794211 TI - Electrode placement, stimulus dosing and seizure monitoring during ECT. AB - Electroconvulsive therapy is one of the most useful, safe and predictable treatment modalities in psychiatry. For optimal results proper application of the procedure is essential. Over the years the procedure has undergone considerable refinement, yet not all those who administer the treatment are fully conversant with this. This paper addresses issues relating to electrode placement, stimulus dosing and seizure monitoring from practical and clinical points of view. Right unilateral ECT, if administered with high electrical stimulus, produces results close to bilateral treatment with substantially less cognitive impairment. However, certain patients may only respond to bilateral ECT. Adequate training for clinicians administering ECT is recommended. PMID- 7794213 TI - Catatonia and ECT. PMID- 7794212 TI - Demographic and readmission data in a therapeutic community for black psychiatric patients in South Africa. AB - Therapeutic communities have an important role in adult psychiatric care. Such a hospital unit is described within a Black psychiatric hospital in South Africa. However, owing to apartheid very few Black clinical psychologists have been trained. Translators frequently have to be used in the therapeutic context, which is an unorthodox approach. Nevertheless, various therapeutic groups are conducted. Demographic and clinical data for a 3 year period are presented, showing most of the patients to be male, unmarried and around 30 years of age. Schizophrenic conditions were the most common diagnoses, with problems of self care and low self-esteem predominating. Although a readmission rate of 22.1% was noted the lack of adequate control measures in this study must be taken into consideration. PMID- 7794214 TI - Dis-attachment. PMID- 7794216 TI - Self harm. PMID- 7794215 TI - Attention deficit disorder. PMID- 7794218 TI - Ritualised self harm in traditional aboriginal society. PMID- 7794217 TI - Serotonin and drug-induced movement disorders. PMID- 7794221 TI - Thermal study of anti-G ensembles aboard F-16 aircraft in hot weather. AB - Continuing advances in the performance of new fighter aircraft have engendered requirements for more sophisticated protective clothing and life support systems. A major goal is prevention of acceleration-induced loss of consciousness. The USAF's Advanced Technology Enhanced Design G-Ensemble (COMBAT EDGE) increases acceleration tolerance by providing positive pressure to the oxygen mask; the work of pressure breathing is reduced by adding a counter-pressure bladder over the chest. However, the addition of impermeable layers over the chest reduces the area available for evaporation of sweat. This study was designed to determine whether COMBAT EDGE (CE) was demonstrably hotter than standard summer flight clothing (ST) during F-16 sorties in hot weather. Eight male pilots served as volunteer subjects, each flying missions at 1430 and 1745 h on two consecutive days, one day with CE and the other with ST. Data were logged at 1-min intervals for rectal temperature (Tre), skin temperatures at the chest and thigh (Tch and Tth) and air temperatures outside the clothing at the same two sites (Tach and Tath). The weather was stable over the 4 d of data collection with highs of 34-36 degrees C and simultaneous dewpoints of 19-23 degrees C (relative humidity 35 45%). The mean Tach was stable at 28 degrees C in flight, while individual means for Tath ranged from 22 to 25 degrees C. The lower value and greater variability at the thigh reflect its proximity to the air conditioning vent. Despite the differences in air temperature, Tch and Tth remained in the range 34-36 degrees C throughout the flights.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794220 TI - Comparison of bifocal and progressive addition lenses on aviator target detection performance. AB - The objective of this project was to determine if the type of presbyopic correction worn by aviators, conventional bifocal versus progressive addition lenses (PAL's), differentially affects aviator visual search performance. Experienced aviators, most with tactical fighter aircraft experience, searched for high-contrast targets under simulated dawn/dust (mesopic) lighting conditions (approximately 3.0 cd/m2) while wearing either a standard bifocal (ST-25) or PAL spectacle correction. Latency of locating high-contrast targets under these viewing conditions was differentially affected by the type of presbyopic correction used. Specifically, compared to a standard bifocal (ST-25), a PAL correction (Varilux Infinity) significantly lowered the time needed to locate static targets at a cockpit instrument viewing distance (83 cm). Accuracy of target location responses was not affected by the type of correction used. In addition, 7 months post-experiment, 7 of the 12 participants (58%) indicated that they used their PAL correction exclusively when flying the T-39 Sabre Liner. Three subjects (25%) used their PAL correction intermittently (primarily at night) when flying and two subjects preferred not to use the PAL's. These results suggest that relative to bifocals, speed of responding to static targets at intermediate viewing distances may be improved by wearing PAL's, and that subjects were able to adapt to PAL lenses quickly in a laboratory setting, using them later in a functional aviation environment. PMID- 7794219 TI - Jet pilot, helicopter pilot, and college student: a comparison of central vision. AB - Jet pilots (JP) (N = 44), helicopter pilots (HP) (N = 29), and college students (CS) (N = 41) were tested with a battery of vision tests designed to assess vision skills important for success as a naval aviator. Tests included measures of reaction time, high-contrast acuity, low-contrast acuity, spot detection, far to-near gaze shift, near-to-far gaze shift, low-contrast acuity with glare, and dark focus. A Multi-Variate Analysis of Variance (MANOVA) compared the vision test performance of the three subject groups (JP, HP, and CS). Only with the Far to-Near test was there no difference among the three groups. On all other tests, JP outperformed CS. The difference between HP and CS was less consistent and less dramatic than the difference between JP and CS. Only with the glare test were CS significantly better than HP. The results were interpreted as reflecting the influence of various selection factors, operational requirements, differential attrition, and age. PMID- 7794222 TI - The effects of tyrosine on cognitive performance during extended wakefulness. AB - Tyrosine, a large neutral amino acid found in dietary proteins, has received recent attention as a potential treatment for stress. The behavioral effects of tyrosine were examined during an episode of continuous nighttime work involving one night's sleep loss. Subjects performed nine iterations of a battery of performance tasks and mood scales for approximately 13 h, beginning at 1930 and ending at 0820. They remained awake throughout the day on which the experiment began and were awake for more than 24 h by the end of testing. Six hours after the experiment began, one-half of the subjects received 150 mg.kg-1 tyrosine in a split dose while the other half received cornstarch placebo in a double-blind procedure. Tyrosine administration was associated with a significant amelioration of the usual performance decline on a psychomotor task and a significant reduction in lapse probability on a high-event-rate vigilance task. The improvements lasted on the order of 3 h. The results of this study also suggest that tyrosine is a relatively benign treatment at this dose. After further testing with other doses and timing of administration, tyrosine may prove useful in counteracting performance decrements during episodes of sustained work coupled with sleep loss. PMID- 7794223 TI - The relationship between the U.S. Navy fleet diver physical screening test and job task performance. AB - The development of job-related selection and training methods will improve safety and lead to substantial cost savings to the U.S. Navy through enhanced screening and productivity. The present investigation determined the extent to which the current U.S. Navy fleet diver physical screening test predicted performance of five representative physically demanding job tasks. Subjects were 146 male diver candidates (age 25.1 +/- 4.3 years, X +/- SD, range 18-37 years) undergoing training at the Naval Diving and Salvage Training Center, Panama City, FL. Results indicate the current U.S. Navy fleet diver physical screening test provides a poor estimate of representative job task performance for the population of diver candidates tested. A finding of particular operational significance was that a substantial number of diver candidates who passed current physical screening test standards were unable to complete (i.e., failed) the tool bag swim (18.5%) and fin-kick (25.7%) tasks. Results suggest the current screening test has limited utility for physical selection purposes and underscore the need for developing a requirements-based selection battery to ensure that diver physical capabilities are aligned to the job. PMID- 7794225 TI - Psychological changes during altitude hypoxia. AB - We examined the effects of altitude hypoxia on the subject's cognitive functions and psychological state. Two assessment approaches were used, a cognitive-motor task and a structured interview. An experimental group of six subjects was tested three times: once under conditions of normoxia, once 8-20 h after a rapid climb to an altitude of 4383 m, and once 48-60 h after ascent to that altitude. A comparison of the experimental group's performance on the cognitive-motor task with that of a control group showed a difference on the second administration: the experimental group's performance did not improve, whereas the control group's performance did. This difference recovered on the third administration. A comparison of the subjects' verbalizations during the three interviews showed that they experienced a strong crisis during the first period at altitude, which improved partially during the second period. Evidence for use of certain defense mechanisms, e.g. self-concern, was found 8-20 h after ascent; both dependent measures were adversely affected. These measures recovered after 48-60 h. PMID- 7794224 TI - Effects of high altitude and cold exposure on resting thyroid hormone concentrations. AB - This study examined the effect of high altitude and cold exposure on thyroid hormone status during a mountaineering expedition. There were 15 males participating in an expedition to climb Mt. McKinley, AK. Resting blood samples were collected and analyzed for thyroid-stimulating hormone (TSH), total (T)-free (f) thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and cortisol. Measurements were made on three occasions: baseline in the continental U.S. one week pre-expedition (PRE-I), baseline in Alaska immediately pre-expedition (PRE II), and immediately upon descent post-expedition (POST). Statistical analysis indicated that no significant trial PRE-I vs. PRE-II (p > 0.05) differences occurred. Significant (p < 0.05) reduction, however, occurred from PRE-II to POST expedition in TSH, TT3, and fT3. Also rT3 and cortisol increased significantly PRE-II to POST while TT4 and fT4 were unchanged. The increase (delta = POST minus PRE-II) in cortisol was negatively correlated with the decrease (delta) in TSH (r = -0.52, p = 0.05) and TT3 (r = -0.49, p < 0.06). Moreover, the reduction in TT3 was inversely correlated with the rT3 increase (delta comparison, r = -0.66, p < 0.01). The findings demonstrate that the resting concentrations of thyroid hormones are disrupted by a mountaineering expedition, specifically an environmental stress-related "low T3 condition" seems to develop. These changes would seem to be related to an impaired peripheral conversion of T4 to T3, possibly brought about by elevations in the circulating cortisol levels. PMID- 7794226 TI - Human tolerance and physiological responses to exercise while breathing oxygen at 2.0 ATA. AB - Multiple physiological functions were monitored in ten men who performed two 30 min periods of 150-W ergometer exercise during 120-min exposures to O2 at 2.0 ATA. There were no convulsions or electroencephalographic manifestations of increased excitability. Sequential measurements of peripheral visual fields, pulmonary mechanical function, mental performance, and cardiovascular function during the resting recovery after each of the two exercise periods were not detectably altered from pre-exercise control values. Pre- and post-exposure measurements of visual acuity, accommodation, pupil diameter, visual cortical activity, and retinal electrical activity also revealed no significant differences. While CNS symptoms were absent, average arterial PCO2 rose by about 5 mm Hg during both exercise periods. This finding was confirmed in six subjects who performed four 6-min periods of continuous exercise at 50, 100, 150, and 200 W while breathing O2 at 2.0 ATA. Average arterial PCO2 rose nearly linearly from 34.3 mm Hg at rest to 44.0 mm Hg at 200 W. Arterial PCO2-related increments in brain blood flow and PO2 may explain part or all of the known detrimental influence of exercise on CNS O2 tolerance. PMID- 7794227 TI - Reciprocity of hemodynamic changes during lower body negative and positive pressure. AB - Lower body negative pressure (LBNP) and lower body positive pressure (LBPP) are two opposite environments for the lower abdomen and lower extremities. We examined RR interval (RRI), blood pressure, forearm blood flow, cardiac output, plasma atrial natriuretic factor, and plasma catecholamines during sequentially administered LBNP and LBPP in order to define the cardiovascular and neuroendocrine reciprocity of these models of orthostasis (LBNP) and anti orthostasis (LBPP). Six healthy young men were studied with a ramped onset of LBNP followed by a similarly ramped LBPP, spaced between periods of data acquisition during rest. Forearm blood flow decreased during LBNP and increased during LBPP. However, LBNP and LBPP did not produce reciprocal changes in cardiac output. No reciprocal changes were found in plasma catecholamines and plasma atrial natriuretic factor. The variability of RRI and systolic/diastolic blood pressures were analyzed within two bandwidths of interest: the low bandwidth, corresponding to the frequency of baroreflex-mediated variability (0.04 to 0.12 Hz), and the high bandwidth, representative of parasympathetically mediated variability at the frequency of respiration (0.22 to 0.28 Hz). The ratio of high to low bandwidth RRI variability was reciprocally diminished during LBNP and increased during LBPP, reflecting a relative decrease in the level of parasympathetic tone during LBNP and an increase during LBPP. In addition, the variability of the DBP within the low baroreflex bandwidth increased during LBNP and decreased during LBPP. The phase lag of RRI variability in relation to BP variability did not change reciprocally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794228 TI - Visually triggered migraine headaches affect spatial orientation and balance in a helicopter pilot. AB - The authors present a case of an attack helicopter pilot with recurrent spatial disorientation (SD) flying with night vision goggles (NVG's), diagnosed as having visually triggered migraine headaches. Serial Dynamic Platform Posturography testing during an acute migraine attack demonstrated balance dysfunction under visual and somatosensory deficient conditions, correlating with headache intensity. Vestibular symptoms are associated with migraine, and may be triggered by visual stimuli. NVG scintillations in susceptible individuals may act as a visual trigger for migraine. Migraine phenomenon may be a contributing factor to SD, especially during NVG operations. The association of visual and vestibular dysfunction with migraine and aeromedical disposition of migraine in aviators is discussed. PMID- 7794230 TI - Predicting human heat strain and performance with application to space operations. AB - This Institute has developed a USARIEM Heat Strain Prediction Model for predicting physiological responses and soldier performance in the heat, which has been programmed for use by hand-held calculators and personal computers, and incorporated into the development of a heat strain decision aid. This model is demonstrated to predict accurately (generally within +/- 1 SD/SEM) rectal temperature (Tre) responses for soldiers wearing various military clothing ensembles during U.S. or non-U.S. military scenarios in the heat at home or abroad. The value of this model is shown presently for three NASA scenarios involving the Launch and Entry Suit (LES). The LES (ventilated or unventilated) is modeled during pre-launch/launch, re-entry/landing, and emergency egress after re-entry/landing scenarios, predominately to evaluate heat acclimation and hydration state effects. During the pre-launch/launch scenario, predicted final Tre closely agrees with observed values suggesting minimal heat strain (Tre approximately 38.0 degrees C). In contrast, dehydrated (3%) unacclimated individuals show moderate levels of heat strain (Tre approximately 38.5 degrees C) for this same scenario. During the re-entry/landing and emergency egress scenarios, dehydrated unacclimated individuals are predicted to exhibit excessive heat strain (Tre > 39.0 degrees C). Thermal tolerance time is predicted to be only 6 min during emergency egress if individuals are dehydrated and unacclimated to heat while wearing the LES. If heat transfer values for space operations clothing are known, NASA can use this prediction model to help avoid undue heat strain involving astronauts for most scenarios during spaceflight. PMID- 7794229 TI - Aeromedical helicopter use following the 1989 Loma Prieta earthquake. AB - OBJECTIVE: To understand the role of aeromedical services in the 1989 Loma Prieta disaster response, a survey was conducted of aeromedical teams participating in the disaster. METHODOLOGY: An investigator interviewed flight team members from all six participating helicopter services. RESULTS: Aeromedical teams transported 31 patients after the earthquake. Of six helicopter teams, four reported landing zone (LZ) hazards. One flight team made determinations of death on five patients at one scene; two teams performed CPR enroute; two teams reported acting as airborne radio repeaters between communication centers, ground field units, and counties. Of six services, four performed over flight reconnaissance. CONCLUSION: Regional disaster managers should incorporate aeromedical services into disaster plans. This planning should include all of the roles played by aeromedical services; patient and equipment transportation, disaster reconnaissance, and communications linkage. Aeromedical services can play an essential role in disaster mitigation. PMID- 7794232 TI - From brandy to antibiotics for peptic ulcer disease. PMID- 7794231 TI - A model to predict carboxyhemoglobin and pulmonary parameters after exposure to O2, CO2, and CO. AB - A computer-based physiological model of respiratory gas exchange, which considered variation in inhaled oxygen and carbon dioxide, was modified to include the effects of inhaled carbon monoxide. Output from the modified model consists of 60 variables, including blood, alveolar and tissue gases, ventilatory function and carboxyhemoglobin. Extensive testing demonstrated that this model produced accurate results for known problems and physiologically plausible results for situations in which the results were not empirically known. Estimates of the effects of simultaneous continuously varying exposure to carbon monoxide, oxygen and carbon dioxide cannot be practically obtained with other extant methods. The modified model receives input from two computer files containing environmental and subject physiological variables. These files allow a continuous dynamic multi-gas exposure simulation or actual exposure data profiles. Up to four outputs can be selected for plotting or stored in a file for later analysis. PMID- 7794234 TI - Motion sickness. PMID- 7794233 TI - You're the flight surgeon. Difficulty in swallowing. PMID- 7794236 TI - Biochemical identification of interbreeding between B-type and non B-type strains of the tobacco whitefly Bemisia tabaci. AB - Polyacrylamide gel electrophoresis and a kinetic microplate assay were used to detect heterozygotes resulting from a cross between B-type and non B-type strains of the whitefly Bemisia tabaci. Both strains were homozygous for different esterase and acetylcholinesterase (AChE) enzymes, and heterozygotes were produced in one of two crosses between B-type females (diploid) and non B-type males (haploid). In reciprocal crosses, however, no female offspring were produced, indicating that fertilization had not occurred. Despite the identification of individuals heterozygous for the esterase and AChE markers, there was clearly a significant degree of reproductive incompatibility between the two strains. The biochemical assays provided a vital component of this study and the advantages of their use are discussed. PMID- 7794235 TI - Mitochondrial DNA variation in North American oedipodinae. AB - Restriction fragment analysis of mitochondrial DNA (mtDNA) was used to examine genetic variation and population structure in 13 species of banded-winged grasshoppers (subfamily Oedipodinae). Total DNA of 246 individuals was digested with 11 restriction enzymes and probed with three cloned EcoRI fragments representing the entire mitochondrial genome of Melanoplus sanguinipes. On average, members of this subfamily were five times more variable than those in another subfamily, Melanoplinae, previously examined. This would appear to lend support to Vickery's claim that the time of origin of Nearctic oedipodines is more ancient than that of melanoplines. With respect to population structure, a few different patterns were exhibited. Species such as Camnula pellucida had populations containing a mixture of haplotypes, some widespread and some geographically restricted. In contrast, Chortophaga viridifasciata populations were characterized by unique assemblages of diverse haplotypes. Phylogeographic hypotheses are advanced to account for these observations. PMID- 7794237 TI - A triose-phosphate isomerase polymorphism in the Atlantic salmon Salmo salar L. AB - Atlantic salmon, Salmo salar L., from four European locations show allelic variation at one of three triose-phosphate isomerase (TPI) loci (TPI-3*) when separated on horizontal starch gel electrophoresis, using either eye or liver extracts. Two common alleles (*100 and *103) and one rare allele (*97) segregate at TPI-3* with unambiguous typing being possible by observing the interlocus heterodimers. Family studies demonstrate that TPI-3* 100 and *103 are of autosomal location and are inherited in a Mendelian fashion. TPI-3* variation can also be typed in adipose fin tissue, allowing nondestructive tissue sampling. Three loci are also active in brown trout, Salmo trutta, with two individuals being homozygous for TPI-3*, as are a small number of S. salar from eastern Canada. The presence of this additional variable allozyme locus in S. salar is important, since genetic studies in that species have been limited by the low level of allozyme variability detectable. PMID- 7794238 TI - Glutathione S-transferase class pi polymorphism in baboons. PMID- 7794239 TI - Expression of the acetylcholinesterase transcript in the chordotonal neurons of Drosophila embryos. AB - The transcript of the acetylcholinesterase gene (Ace) was detected in the central nervous system (CNS) and the lateral chordotonal neurons (lch3, lch5) of wild type Drosophila melanogaster embryos. Ace126, a representative mutation of the acetylcholinesterase gene, abolished expression in the lch3 and lch5 neurons and slightly reduced the number of lch5 cells in some abdominal segments. The number of lch5 neurons was also reduced in Ace hemizygous and transheterozygous mutant embryos. The correlation between the lack of Ace expression and the mild defect of lateral chordotonal neurons is discussed. PMID- 7794240 TI - Analysis of genetic diversity of domestic cattle in east and Southeast Asia in terms of variations in restriction sites and sequences of mitochondrial DNA. AB - There are three major groups of domestic cattle in East and Southeast Asia: European cattle, Zebu cattle, and Bali cattle. Ten restriction enzymes were used to analyze restriction site variants in the mitochondrial DNA (mtDNA) in 178 individuals belonging to these three groups of cattle. The results indicate that each of the three groups has mtDNA with a specific haplotype. The sequence of the mitochondrial gene for cytochrome b in representative haplotypes of Zebu and Bali cattle was determined and was compared with that of European cattle in the literature. We calculated 51 pairwise nucleotide sequence differences between European and Zebu cattle and 91 between European and Bali cattle. Our results suggest that ancestral populations of Asiatic domestic cattle may have diverged into two lineages--Bali and European plus Zebu--more than 3 million years ago, and then the European and Zebu groups diverged more than 1 million years or so before domestication occurred. PMID- 7794242 TI - Amyloid P component promotes aggregation of Alzheimer's beta-amyloid peptide. AB - Amyloid P component (AP) has been recognized as a beta-amyloid-associated protein but the pathological role is not known. In the present experiments, it has been shown that AP promotes the aggregation of Alzheimer's beta-amyloid peptide (A beta) in the presence of a physiological concentration of Ca2+. The aggregation promotion was observed at a concentration of soluble A beta 1-40 in human cerebrospinal fluid. The results suggest that AP is possibly a pathogenic factor of the cerebral amyloidosis. PMID- 7794243 TI - Change in variant transthyretin levels in patients with familial amyloidotic polyneuropathy type I following liver transplantation. AB - Three patients with familial amyloidotic polyneuropathy (FAP) type I underwent liver transplantation from heart-beating cadaveric donors. Since 2 patients underwent blood transfusion during the operation, variant transthyretin (TTR) levels in the plasma did not decrease time dependently. However, in 1 patient without blood transfusion variant TTR levels decreased in a time dependent manner and plasma half life of variant TTR was calculated to be 2.1 days. Total protein, normal, and variant TTR levels in cerebrospinal fluid (CSF) remained unchanged after liver transplantation. PMID- 7794244 TI - Luminescence of aequorin is triggered by the binding of two calcium ions. AB - The photoprotein aequorin, capable of emitting light in the presence of a trace amount of Ca2+, is a useful indicator for studying intracellular calcium. The primary structure of aequorin indicated the presence of three Ca(2+)-binding sites, whereas log-log plots of the luminescence intensity versus Ca2+ concentration gave slopes ranging from 2 to 3 depending on the conditions used, suggesting the involvement of two or three Ca2+ ions in the luminescence reaction. Accurate information on the stoichiometry of Ca2+ is essential in interpreting the assay results obtained with aequorin. This study clearly shows that aequorin luminescence is triggered by the binding of two Ca2+ ions, based on the results of titrating aequorin with Ca2+. PMID- 7794247 TI - Cloning of salicylate hydroxylase gene and catechol 2,3-dioxygenase gene and sequencing of an intergenic sequence between the two genes of Pseudomonas putida KF715. AB - The salicylate hydroxylase can convert the salicylate to catechol, and catechol 2,3-dioxygenase catalizes the conversion of catechol to 2-hydroxymuconic semialdehyde. A salicylate hydroxylase gene and a catechol 2,3-dioxygenase have been cloned from chromosomal DNA of P. putida KF715. The two genes have different promoters. An open reading frame with 339 nucleotides preceded by a putative ribosome-binding sequence (GGAGG) was identified in the intergenic sequence between salicylate hydroxylase gene and catechol 2,3-dioxygenase gene of P. putida KF715 and its sequence analyzed. This open reading frame can encode a polypeptide of molecular weight 13 kDa containing 112 amino acids, whose sequence exhibited 87% homology with that of ferredoxin encoded in NAH7 of P. putida PpG7 and significant homology with those of redox components in phenol hydroxylase, benzoate 1,2-dioxygenase, toluate 1,2-dioxygenase, xylene monooxygenase, and toluene 4-monooxygenase. PMID- 7794241 TI - Exon organization and sequence of the genes encoding alpha-lactalbumin and beta lactoglobulin from the tammar wallaby (Macropodidae, Marsupialia). AB - Clones encompassing the genes encoding alpha-lactalbumin and beta-lactoglobulin were isolated from a tammar wallaby genomic library, the exons localized using end-labeled oligonucleotides and the DNA sequences determined. The tammar beta lactoglobulin gene has the same 7 exon-6 intron structure as the sheep homologue. Potential binding sites for mammary gland-specific transcription factors were identified, on the basis of similarity to sites in the sheep gene, in the promoter region of the tammar beta-lactoglobulin gene. The tammar gene encoding alpha-lactalbumin appears to contain four introns rather than three as are present in the eutherian homologues, or the evolutionarily related lysozyme gene. The additional intron appears to occur within the 5' noncoding region of the tammar gene. PMID- 7794245 TI - Deletion and site-directed mutagenesis of EF-hand domain of phospholipase C-delta 1: effects on its activity. AB - In order to elucidate a role of a putative EF-hand motif (144-172) in phospholipase C-delta 1 (PLC-delta 1), deletion and point mutation of the enzyme were performed and the mutated cDNAs were expressed in CHO cells and E. coli AD202 strain. Deletion of amino acid residues of 141-236 or 173-236 resulted in abolition of PLC activity. However, the decreased PLC activity to 15-20% by deletion of the EF-hand motif (144-172) was still Ca(2+)-dependent. Furthermore, mutants, in which conserved Asp153, Asp157, Glu164 or all these acidic amino acids in the EF-hand motif were replaced with alanine residues, showed nearly the same PLC activity and Ca(2+)-dependency as those of wild-type. These results suggest that the region containing the EF-hand motif may not play a role in regulation of Ca(2+)-sensitivity of PLC-delta 1, but is important for its activity. PMID- 7794249 TI - Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. AB - ISP-1/myriocin is a new type of remarkably potent immunosuppressant, the structure of which is homologous to sphingosine. ISP-1/myriocin inhibited the proliferation of an IL-2-dependent mouse cytotoxic T cell line, CTLL-2, at nanomole concentrations. ISP-1/myriocin inhibits serine palmitoyltransferase activity at picomole concentrations. This enzyme catalyzes the first step of sphingolipid biosynthesis and reduces the intracellular pool of sphingolipid intermediates. The growth inhibition induced by ISP-1/myriocin was completely abolished by the addition of sphingosines or sphingosine-1-phosphate, but not by sphingomyelin or glycosphingolipids. These results suggest that sphingosines or sphingosine-1-phosphate are associated with CTLL-2 proliferation, and ISP 1/myriocin suppresses T cell proliferation by the modulation of sphingolipid metabolism. ISP-1/myriocin should be a useful tool for the study of the sphingolipid pathway, which has been associated with various kinds of signal transduction. PMID- 7794248 TI - Active-site analysis of ferric P450 enzymes: hydrogen-bonding effects on the circular dichroism spectra. AB - Active-site CD spectra were analyzed for P450's with known x-ray structures (P450terp, P450BM-3, P450cam). CD spectral patterns for Fe(3+)-substrate-free P450's reflect structure/function properties of the distal pocket. P450terp and P450BM-3 have an H-bond between 6th ligand and I-helix [Hasemann, C.A., et al. (1995) Structure, 3, 41-62], and the Soret CD band at approximately 410 nm is approximately 2-fold larger than that at approximately 350 nm. For P450cam, the two CD bands are more nearly equal, and the 6th ligand is not H-bonded to the I helix. The CD spectral pattern can be used to predict active-site structural properties, e.g., H-bonding and polarity. PMID- 7794246 TI - Plasma nitric oxide end products are increased in the ischemic canine heart. AB - Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia. PMID- 7794251 TI - Translocation of recombinant p47phox cytosolic component of the phagocyte oxidase by in vitro phosphorylation. AB - Activation of superoxide-generating NADPH oxidase system of human neutrophils involves phosphorylation-dependent translocation of p47phox and other cytosolic components to the plasma membrane. In contrast to the stimulation of the NADPH oxidase in intact cells, however, the activation of cell-free system requires the addition of anionic amphiphiles such as sodium dodecyl sulfate (SDS) and arachidonate. In this system, translocation of p47phox is also an essential step for activation, but phosphorylation is not required. The basis of this difference in oxidase activation is not yet clear. We now report that in a cell-free oxidase system, phosphorylated recombinant p47phox can be translocated to the membrane in the absence of SDS or arachidonate. These findings suggest that both phosphorylation and SDS could cause a common change in conformation or charge of p47phox that may result in the association of p47phox with the plasma membrane. PMID- 7794250 TI - Homozygous deletions of the MTS1 gene are rare in non-astrocytic brain tumors. AB - Several studies support a role for the multiple tumor suppressor gene (MTS1) in the malignant progression of different tumor types. In this study we have examined the status of the MTS1 gene in a variety of non-astrocytic tumors of the central nervous system. It was not possible, using multiplex PCR with primers for MTS1 and D9S196, a chromosome 9q marker, to demonstrate deletions of MTS1 in 59 primary non-astrocytic tumors. Two out of 5 (40%) secondary tumors showed evidence of homozygous deletion of MTS1. The results obtained here for primary non-astrocytic tumors contrast with those previously described for astrocytic tumors where a high frequency of deletions of MTS1 was associated with tumor progression. PMID- 7794252 TI - The neuroendocrine protein 7B2 acts as a molecular chaperone in the in vitro folding of human insulin-like growth factor-1 secreted from yeast. AB - The neuroendocrine protein 7B2 prevents premature activation of PC2, an enzyme involved in the processing of prohormones in the secretory pathway. We inquired if this chaperone-like function encompasses a broader role for 7B2 in the folding of hormone-like proteins. As a test, the fate of misfolded human insulin-like growth factor-1 (IGF1) was assessed, in the presence and absence of 7B2. Most of the recombinant IGF1 molecules, secreted from yeast, are a conglomeration of inactive multimers which are either disulfide-linked or mere physical aggregates. We find that yeast-produced 7B2 influences the in vitro conversion of inactive molecules into active monomers. However, the amounts of disulfide-linked dimers remain unaffected during this conversion. Interestingly, both 7B2 and the molecular chaperone DnaK interact with IGF1 in the yeast two-hybrid system. Like DnaK, 7B2 also binds the tumor suppressor protein p53. Binding of DnaK to exposed epitopes of aggregated proteins is known to be a prerequisite for deaggregation. It is conceivable that 7B2 participates in an analogous manner in the dissociation of non-covalently linked multimers of IGF1. Our results indicate that 7B2 might find an application in the deaggregation of potentially useful therapeutic proteins. PMID- 7794253 TI - Evidence for the presence of functional thyrotropin receptor in cardiac muscle. AB - There is increasing evidence that the membrane-bound thyrotropin receptor (TSHR) may be mediating clinically important direct effects of thyrotropin (TSH) and of TSHR antibodies (TSHRab) in extra-thyroidal tissues. TSHR mRNA has formerly been detected in thyroid, retroorbital muscle and fibroblasts, peripheral lymphocytes and rodent fat. It is well known that thyroid disease may aggravate or induce heart disease, but the pathophysiological role of TSH and TSHRab is not clear. The aim of this study was to investigate if TSHR is present in cardiac muscle. Reverse transcriptase polymerase chain reactions revealed TSHR in human heart and Northern blot on extracted RNA showed a RNA species of 4.4 kb. TSH stimulation of cultured mouse AT-1 cardiomyocytes elevated the levels of intracellular second messenger 3',5'-cyclic AMP. This effect of TSH could be inhibited by TSHR antibodies. In solution hybridization levels of TSHR mRNA in AT-1 cells were 50% of mRNA in crude mouse heart. In conclusion functional TSHR is present in cardiomyocytes. PMID- 7794254 TI - Depletion of intracellular calcium stores triggers transplasmamembrane chloride influx in human lymphocytes: regulation by tyrosine kinase. AB - The capacitative regulation of intracellular chloride concentration ([Cl-]i) was measured in intact human lymphocytes using the Cl(-)-sensitive fluorescence dye 6 methoxy-1-(3-sulfonato-propyl)-quinolinium (SPQ). The fluorescence was measured at 433 nm with the excitation wavelength of 344 nm. The emptying of intracellular Ca2+ stores after the specific inhibition of the endoplasmic Ca2+ ATPase by thapsigargin produced a concentration-dependent transplasmamembrane Cl- influx. The thapsigargin-induced Cl- increase was also seen in the absence of extracellular Ca2+, but it was significantly reduced after the addition of the Cl exchange blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The thapsigargin-induced Cl- increase was significantly reduced after the specific inhibition of tyrosine kinase by genistein or tyrphostin A25. It is concluded that the depletion of intracellular Ca2+ pools triggers transplasmamembrane Cl- influx by a tyrosine kinase-dependent mechanism. PMID- 7794256 TI - Leucine zipper-like domain regulates the autophosphorylation and the transforming activity of P130gag-fps. AB - P130gag-fps, the product of Fujinami sarcoma virus, has a leucine zipper (LZ) motif located in 729-756 amino acid residues. To explore the role of LZ-like domain in the transformation by P130gag-fps, we made a deletion (delta FpsLZ/SH2) and a site-directed substitution mutation (L746P). Deletion mutant did not transform the 3Y1 cells and the resulting protein did not show kinase activity. Substitution of Leu746 with Pro (L746P) reduced the transforming activity by 6 fold. Although the L746P mutant retained intact catalytic activity in vitro, it did not phosphorylate cellular proteins in vivo. We concluded that LZ-like domain might mediate the trans-activation of P130gag-fps tyrosine kinase by autophosphorylation, which is prerequisite for the transforming activity. PMID- 7794255 TI - Determination of a necdin cis-acting element required for neuron specific expression by using zebra fish. AB - To determine cis-acting elements required for neuron specific expression of a necdin gene, we tried to use zebra fish assay system in vivo instead of cell lines in vitro. Various expression vectors carrying upstream sequences of necdin gene fused to MEKA (lacZ) gene as a reporter were injected into fertilized zebra fish embryos and then the expression of the reporter gene was analyzed by the whole mount immunochemical method. No promoter activity was obtained with a construct carrying sequence from -63 to +63 of the necdin gene, while promoter activity with preferential skin expression was obtained with a construct having sequence from -86 to +28. Further upstream sequence from -173 to +28 exhibited neuron specific expression as well as that from -845 to +63. These results indicate that a cis-acting element responsible for neuron specific expression is located in an 87bp sequence from -173 to -87 of necdin gene. PMID- 7794257 TI - Effect of P2Y-purinoceptor stimulation on renal gluconeogenesis in rats. AB - In the freshly prepared rat renal cortical tubule suspension, the effects of ATP on intracellular free calcium mobilization and gluconeogenesis were investigated. ATP increased intracellular free calcium concentration ([Ca2+]i) in a dose dependent manner (10(-6) - 10(-3) M). The rank order in the potency of ATP analogs at 10(-4) M was 2-methylthio ATP > ATP > or = ADP. AMP, adenosine and alpha, beta-methylene ATP did not respond to [Ca2+]i. These results suggest that P2-purinoceptor in the rat kidney cortex should be specifically P2Y subtype. Renal gluconeogenesis from pyruvate was stimulated maximally by 10(-4) M ATP (48.3 +/- 13.2%). This effect was significantly inhibited by 10(-4) M suramin. Thus, the present study suggests that renal gluconeogenesis is increased via P2Y specific purinoceptor stimulation. PMID- 7794258 TI - Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats. AB - A responsible gene of genetically obese (ob/ob) mouse has recently been isolated. Genetic disruption of ob gene causes massive obesity. To elucidate the pathophysiological regulation of ob gene, we examined the gene expression in fat tissues of a non-genetical obese model, VMH-lesioned rats. The ob mRNA was identified in both subcutaneous and mesenteric fat tissues in the control rats. In VMH-lesioned rats, the abundance of ob mRNA increased after the gain of body weight and marked expression was observed on 15th day after making VMH lesion. These data suggest that ob gene might be up-regulated with fat accumulation even in non-genetically obese animals. PMID- 7794260 TI - Differential expression patterns of beta-actin mRNA in cells undergoing apoptosis. AB - Microfilaments play an important role in the formation of apoptotic bodies. This study examined expression patterns of beta-actin, a key component of microfilament, during apoptosis. The data suggest that continuous beta-actin expression is not required for formation of apoptotic bodies. beta-actin mRNA levels rapidly declined in HL-60 cells following induction of apoptosis by actinomycin D, but were transiently elevated by two other apoptosis-inducing agents, cycloheximide and ionophore A23187. Furthermore, changes in beta-actin mRNA levels were less marked in U937 cells in which apoptosis was also induced by actinomycin D, as well as in WISH cells which demonstrated no typical apoptotic characteristics following actinomycin D treatment. PMID- 7794259 TI - Lysophosphatidic acid activates phosphoinositide 3-kinase and phospholipase C in human platelets: inhibitory effects of Wortmannin on phosphoinositide 3-kinase and aggregation. AB - Lysophosphatidic acid is a biologically active serum phospholipid known to have growth factor-like activities and to cause platelet aggregation. Activated phosphoinositide 3-kinase has been suggested to be involved in cytoskeletal reorganization and mitogenesis. We report that lysophosphatidic acid causes platelet phosphoinositide 3-kinase activation, leading to accumulation of phosphatidylinositol (3, 4, 5) P3 and phosphatidylinositol (3, 4) P2, and stimulates phospholipase C. Worthmannin, a potent inhibitor of phosphoinositide 3 kinase, blocks platelet aggregation induced by lysophosphatidic acid without impairing phospholipase C activation. Eristostatin, an antagonist of fibrinogen binding to platelet integrin, completely blocks platelet aggregation without inhibiting phosphoinositide 3-kinase or phospholipase C. We suggest that lysophosphatidic acid, in activating phosphoinositide 3-kinase, promotes platelet aggregation, but that platelet aggregation in response to lysophosphatidic acid does not significantly enhance phosphoinositide 3-kinase activation. PMID- 7794262 TI - Sickling in vitro at venous and arterial oxygen tensions of reticulocytes from patients with sickle cell disease. AB - Sickling of reticulocytes and mature erythrocytes from patients with sickle cell disease was compared at venous and arterial oxygen tensions (PO2 = 30 and 90 mm Hg). Reticulocyte-rich fractions (d < 1.06) were partially deoxygenated in two ways after incubation at PO2 = 180 mm Hg: (1) PO2 of 30 mm Hg for 1 hour, and reoxygenation to 90 mm Hg for 2 hours and (2) PO2 of 90 mm Hg and kept for 2 hours. Percentages of sickled cells were always higher (3-5 times) in reticulocytes than in mature erythrocytes. Percentage of sickled reticulocytes measured at PO2 = 90 mm Hg after partial deoxygenation to PO2 = 30 mm Hg was 2 times higher than that obtained directly at PO2 = 90 mm Hg. In contrast, there was no difference in percentage of sickled cells in the mature erythrocyte population under the two experimental conditions. These results suggest that reticulocytes are more susceptible to sickling under venous oxygen tension and less likely than mature erythrocytes to resume discoidal shape even at arterial oxygen tension. PMID- 7794261 TI - CYP1A2 and 2E1 expression in rat liver treated with combined inducers (3 methylcholanthrene and ethanol). AB - The effects of combined ethanol and 3-methylcholanthrene treatment on rat hepatic cytochrome CYP1A2 and CYP2E1 expression were evaluated. Such a treatment attempts to mimic the simultaneous consumption of ethanol and cigarette smoke. Treatments involving 3-methylcholanthrene and combined ethanol + 3-methylcholanthrene decreased both CYP2E1 expression at the mRNA level (0.6 and 0.4 fold versus controls, respectively) and protein level (0.6 and 0.9 fold versus controls, respectively), while dramatically increasing CYP1A2 expression. Furthermore, combined treatment provokes a synergistic induction of CYP1A2 expression as determined by its catalytic activity and protein content. PMID- 7794263 TI - Membranes of human neuroblastoma SH-SY5Y cells contain specific binding sites for [3H]K-252A. AB - K-252a and the structurally similar compound staurosporine promote neurotrophic responses in several cell lines (PC12, SH-SY5Y human neuroblastoma) and in cultures of primary neurons. The molecular mechanisms involved in the induction of these neurotrophic activities are unknown. It is demonstrated in this report that [3H]K-252a binds to SH-SY5Y membranes and that the binding is specific and saturable with a Kd of 2.7 nM and a Bmax of 100,000 sites per cell. The association of [3H]K-252a with its binding site is rapid and reversible, and the binding was inhibited by unlabeled K-252a and by staurosporine. Binding of [3H]K 252a was not inhibited by the potent protein kinase C (PKC) inhibitor GF109203X. Down regulation of PKC by treating SH-SY5Y cells with a phorbol ester did not cause a reduction in the specific binding of [3H]K-252a to membranes, suggesting that the binding is not to PKC. Treatment of the SH-SY5Y membranes with trypsin and by boiling destroyed all specific binding of [3H]K-252a. These results suggest that the [3H]K-252a binds to a specific protein site that is associated with membranes of SH-SY5Y cells. PMID- 7794264 TI - Regulation of FGF-4 enhancer activity by transcription factor NF-Y. AB - Regulation of FGF-4 gene expression is controlled both by elements in the promoter and by an enhancer domain located in the untranslated region of the third exon. We have determined that transcription factor NF-Y binds to the FGF-4 promoter. We further show by mutational analysis that binding of NF-Y is essential for FGF-4 enhancer activity but has minimal effect on activity of the FGF-4 promoter alone. PMID- 7794265 TI - Catalytic properties of the two active sites of angiotensin I-converting enzyme on the cell surface. AB - Angiotensin I converting enzyme is a zinc metallopeptidase that contains two very similar domains, each with an active site. Enzymatic studies of these active sites have always been performed on solubilized enzyme, although angiotensin I converting enzyme is a transmembrane ectopeptidase. The availability of transfected CHO cells expressing wild-type recombinant enzyme and mutants in which one of the two active sites has been inactivated by site-directed mutagenesis allowed the properties of each active site on the cell surface and the effect of anchorage and membrane environment to be studied. Both active centers are catalytically active in the cell membrane-anchored enzyme and convert angiotensin I to angiotensin II. Comparison of the kinetic parameters for the transfected cells with those for the purified enzymes reveals differences in Kcat but suggests that no major conformational changes of these active sites occur upon anchorage of the enzyme to the cell membrane. The chloride activation profiles show that the two domains in the cell-bound enzyme also undergo the same anion-induced conformational changes as in the solubilized enzyme. PMID- 7794266 TI - Inhibitors of phosphoinositide 3-kinase block exocytosis but not endocytosis of transferrin receptors in 3T3-L1 adipocytes. AB - The role of PI 3-kinase in transferrin receptor recycling was investigated in 3T3 L1 adipocytes. Wortmannin, a specific PI 3-kinase inhibitor, blocked insulin stimulated recruitment of transferrin receptors to the plasma membrane (IC50 approximately 5-15 nM) with a similar potency to its inhibitory effects on PI 3 kinase and glucose transport. Wortmannin also blocked insulin stimulated recruitment of IGF-2 receptors to the cell surface. However, wortmannin (up to 200 nM) and another PI 3-kinase inhibitor, LY294002 (3 micrograms/ml), did not block transferrin receptor endocytosis. This demonstrates that while PI 3-kinase may be necessary for insulin stimulated exocytosis, it is not necessary for endocytosis of transferrin receptors. PMID- 7794267 TI - Purification and some of the properties of a novel secondary alcohol dehydrogenase from Alcaligenes eutrophus. AB - Alcaligenes eutrophus utilizing nerolidol, a sesquiterpene alcohol, as the sole source of carbon contains an inducible NAD(P)(+)-linked secondary alcohol dehydrogenase (SADH). The enzyme was purified to homogeneity by a combination of salt precipitation, ion exchange and affinity matrix chromatographies. The apparent molecular mass of the enzyme was estimated to be 139 KDa with four identical subunits of 38.5 KDa. The enzyme carried out both oxidation and reduction reactions. At pH 5.5, enzyme catalyzed the stereospecific reduction of prochiral ketones to secondary alcohols. The pH optimum for the oxidation reaction was 9.5. NADP+ and NADPH were respectively preferred over NAD+ and NADH for oxidation and reduction reactions. Some of the properties of this enzyme were found to be significantly different from those thus far described. PMID- 7794268 TI - Peritoneal macrophages from stroke-prone spontaneously hypertensive rats accumulate more cholesteryl ester than do macrophages from Wistar-Kyoto rats. AB - The intracellular cholesterol metabolism of peritoneal macrophages from stroke prone spontaneously hypertensive rats (SHRSP) was compared to that of normotensive Wistar-Kyoto rats (WKY) in order to examine the role of macrophages in the development of arterial fat deposits in the SHRSP. Scavenger receptor activity and intracellular acyl CoA:cholesterol acyltransferase (ACAT) activity were significantly higher in macrophages from SHRSP compared to findings in WKY, in the presence of modified low-density lipoprotein (LDL), acetylated-LDL (Ac LDL). Moreover, macrophages from the SHRSP accumulated more cholesteryl ester than seen in WKY in response to Ac-LDL. ACAT activity and cholesteryl ester accumulation were inhibited by specific ACAT inhibitor, HL-004, to a similar extent, in macrophages from WKY and SHRSP. These findings suggest the susceptibility of SHRSP to arterial fat deposits. PMID- 7794270 TI - A novel Ca2+/calmodulin-dependent protein kinase lacking autophosphorylation activity in the rabbit heart. AB - We report the discovery, semi-purification and characterization of a novel Ca2+/calmodulin-dependent protein kinase (peak I kinase) using syntide 2 as a substrate from the rabbit heart. In the study of dependence of peak I kinase on the concentration of calmodulin, half-maximal activation was obtained at approx. 2.0 x 10(-7) M calmodulin. Peak I kinase did not undergo autophosphorylation. This kinase phosphorylates the synthetic peptides such as syntide 2, autocamtide 2, site 3 in a Ca2+/CaM-dependent manner, but not myosin light chain-peptide, gamma-peptide, and cAMP Response Element Binding Protein (CREB) peptide. Elongation Factor-2, alpha-casein and histone-IIIs were not phosphorylated. These data indicate that this CaM kinase is different from other identified Ca2+/calmodulin-dependent protein kinases and therefore constitutes a novel protein kinase. PMID- 7794269 TI - Human colon cancer cell lines permanently expressing alpha 2,6-sialylated sugar chains by transfection with rat beta-galactoside alpha 2,6 sialyltransferase cDNA. AB - A role of alpha 2,6-linked sialic acid in the development of an invasive phenotype in colon cancer has been suggested by several observations but never conclusively demonstrated. An experimental model to clarify this tissue was established by the creation and characterization of a bank of cell lines that differ mainly, if not exclusively, in the degree of alpha 2,6-sialylation. Human colon cancer cell lines SW48 and SW948, normally unable to elaborate the alpha 2,6-sialyl linkage, were transfected with the beta-galactoside alpha 2,6 sialyltransferase (alpha 2,6ST) cDNA driven by the cytomegaloviral promoter and screened for cell surface alpha 2,6-sialylated sugar chains using fluorescein isothiocyanate-conjugated Sambucus nigra agglutinin (SNA-FITC). A panel of SNA FITC-positive clones was established that expresses alpha 2,6ST activity of varying degrees. Only the SNA-FITC-positive recombinants express the 1.2 Kb mRNA predicted to be generated from the transfected sequence. No 4.3-4.7 Kb transcripts that are indicative of transcription from the native alpha 2,6ST gene were detected. PMID- 7794271 TI - The guinea pig histamine H2 receptor: gene cloning, tissue expression and chromosomal localization of its human counterpart. AB - The guinea pig is the prototypic animal species for the histamine H2 receptor. Using a strategy based upon nucleotide sequence homology and starting from the sequence of the rat histamine H2 receptor (Ruat et al., Biochem. Biophys. Res. Commun. 1991, 179: 1470-78), we have cloned an intronless highly homologous DNA very likely encoding the guinea pig H2 receptor. The encoded 359 amino acid protein displays 83 to 86% identity with the rat-, human- or dog-H2 receptors. Northern blot analysis identified a single transcript of 4.6 kb in peripheral tissues and brain areas in which the presence of the H2 receptor had been revealed previously by either photoaffinity labeling or binding studies. In brain, the distribution of transcripts, established by either Northern blots or in situ hybridization studies, was consistent with the localization of the H2 receptor. In addition, using Southern analysis of a chromosome mapping panel constructed from human x hamster hybridomas, we assigned the H2 receptor gene to human chromosome 5. PMID- 7794272 TI - Differential expression and mutation of NME genes in autologous cultured human melanoma cells with different metastatic potentials. AB - The putative metastasis suppressor genes, NME1(nm23-1) and NME2(nm23-2), were examined in a model system we developed to approximate the dissemination of melanoma from a primary skin tumor. We utilized two autologous human melanoma cell lines, IV Cl 1 and IV Cl 3, which displayed qualitatively different metastatic phenotypes following subdermal inoculation into nude mice. Highly metastatic IV Cl 1 cells expressed approximately 5 fold lower levels of protein encoded by NME genes than non-metastatic IV Cl 3 cells. Similar differences in NME protein levels were observed in tumors induced by the two cell lines in nude mice. There were no differences in NME mRNA levels between these two cell lines, suggesting that expression of these proteins is regulated at a post transcriptional level. We found a ser122-pro mutation in the NME2 gene of metastatic IV Cl 1 cells. A similar ser120-gly mutation in NME1 has been found in human neuroblastoma, suggesting that mutation in this region may be a general phenomenon related to tumor progression. These mutations may have functional consequences since they eliminate potential phosphorylation sites and may affect the tertiary structure of mature protein complexes. PMID- 7794273 TI - Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme. AB - Stratum corneum chymotryptic enzyme (SCCE) is a new human serine proteinase expressed by keratinocytes in the epidermis. Its function may be to catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous sheeding of cells from the skin surface. In this work the primary substrate specificity of recombinant SCCE was determined with oxidized bovine insulin B chain as substrate. Cleavage products were separated with high performance liquid chromatography and analyzed by amino acid sequence analysis and mass spectrometry. Cleavage sites were localized to Leu 6-cysteic acid 7, Tyr 16-Leu 17, Phe 25-Tyr 26, and Tyr 26-Thr 27 in insulin B chain. It is concluded that SCCE belongs to the family of serine endoproteinases specific for amino acid residues with aromatic side chains in the P1 position. PMID- 7794275 TI - Potent inhibition of breast cancer cell lines by the isoflavonoid kievitone: comparison with genistein. AB - The isoflavonoid kievitone potently inhibited the proliferation of the oestrogen receptor (ER)-positive breast cancer cell lines MCF-7 and T47D and the ER negative breast cancer cell line SKBR3 (IC50 values 5-18 microM). DNA synthesis of MCF-7 cells stimulated by insulin-like growth factor 1, insulin-like growth factor 2, basic fibroblast growth factor or transforming growth factor alpha was inhibited by similar concentrations of kievitone (IC50 values 1-3 microM). DNA synthesis stimulated by 17, beta-oestradiol was also inhibited (IC50 = 6 microM). Compared with kievitone, genistein was 3-9 fold weaker as an inhibitor of the proliferation of the breast cancer cell lines and of growth factor-stimulated DNA synthesis. However, genistein was about 5-fold more potent than kievitone as an inhibitor of solubilised epidermal growth factor (EGF) receptor kinase activity and EGF receptor autophosphorylation. PMID- 7794276 TI - Calculated effects of the chemical environment of 2-phospho-D-glycerate on the pKa of its carbon-2 and correlations with the proposed mechanism of action of enolase. AB - The mechanism of action of enolase requires drastic lowering of the pK of the alpha carbon of the substrate to enable removal of the alpha hydrogen. Calculations suggest this is done primarily by rotation of the carboxyl ("carbon 1") of the substrate around the carbon-1 carbon-2 bond by 90 degrees so that its oxygen atoms lie in the plane formed by the three carbon atoms and secondarily by effectively neutralizing the negative charges on the carboxylate and phosphate. These predictions are in very good agreement with the proposed mechanism of action of enolase which is based on X-ray crystallographic data. PMID- 7794274 TI - Farnesol is utilized for protein isoprenylation and the biosynthesis of cholesterol in mammalian cells. AB - Evidence has been obtained indicating that free farnesol (F-OH) can be utilized for isoprenoid biosynthesis in mammalian cells. When rat C6 glial cells and an African green monkey kidney cell line (CV-1) were incubated with [3H]F-OH, radioactivity was incorporated into cholesterol, ubiquinone (CoQ) and isoprenylated proteins. The incorporation of label from [3H]F-OH into cholesterol in C6 and CV-1 cells was blocked by squalestatin 1 (SQ) which specifically inhibits the conversion of farnesyl pyrophosphate (F-P-P) to squalene. This result strongly suggests that cholesterol, and probably CoQ and protein, is metabolically labeled via F-P-P. SDS-PAGE analysis of the delipidated protein fractions from C6 and CV-1 cells revealed several labeled polypeptides. Consistent with these proteins being modified by isoprenylation of cysteine residues. Pronase E digestion released a major labeled product with the chromatographic mobility of [3H]farnesyl-cysteine (F-Cys). A different set of polypeptides was labeled when C6 and CV-1 cells were incubated with [3H]geranylgeraniol (GG-OH). Both sets of proteins appear to be metabolically labeled by [3H]mevalonolactone, and [3H]-labeled F-Cys and geranylgeranyl cysteine (GG-Cys) were liberated from these proteins by Pronase E treatment. These cellular and biochemical studies indicate that F-OH can be used for isoprenoid biosynthesis and protein isoprenylation in mammalian cells after being converted to F-P-P by phosphorylation reactions that remain to be elucidated. PMID- 7794277 TI - The "in vitro motility assay" and phalloidin-F-actin. AB - We have compared the osmotic properties of the hydrated, native actin filament and of hydrated phalloidin-F-actin. We have found that phalloidin-F-actin interacts much more strongly with water than native F-actin. It is therefore very likely that the interaction with myosin (that requires the expulsion of the protein solvation water) is more problematic for phalloidin-F-actin that for native F-actin. We conclude that phalloidin-F-actin is not a bona fide substitute for native F-actin in the "in vitro motility assay". PMID- 7794279 TI - Chloride channels in brown adipocyte plasma membranes: candidates for mediation of alpha 1-adrenergic depolarization? AB - The presence of plasma membrane Cl- channels was investigated in brown-fat cells differentiated in culture. Single channel activity was followed by the patch clamp technique, with an NMDG+ Cl- pipette solution and a NaCl bath solution. Only rarely was putative Cl- channel activity encountered in the cell-attached mode. However, after excision, ion channel activity of two types was observed in inside-out patches: one type represented the earlier observed non-selective cation channel, and one a putative Cl- channel, with the following characteristics: practically non-rectifying current-voltage relationship with a conductance of approximately 50 pS and a reversal potential of approximately 0 in symmetrical Cl- solutions, voltage dependent channel activity (Po approached 0.5 at positive holding potentials), and rapid flickering activity in the open state. It is discussed whether this Cl- channel may be responsible for the initial depolarization phase observed after alpha 1-adrenergic stimulation of brown-fat cells. PMID- 7794278 TI - Recombinant expression of hepatitis A virus protein 3A: interaction with membranes. AB - The function of hepatitis A virus (HAV) protein 3A and its structural requirements were studied in vitro and in a bacterial expression system by comparing the polypeptide precursor 3AB derived from a cytopathogenic strain with that of an attenuated strain. Although the precursor polypeptides 3AB of both HAV strains bind to microsomal membranes after translation in vitro they differ in inducing membrane permeability when expression is induced in bacteria. Intake and release of macromolecules was dramatically increased when 3AB of the cytopathogenic strain was expressed. Amino acid sequence alignments suggest that membrane binding might be due to a hydrophobic stretch near the C-terminus of 3A found in all picornaviruses whereas the ability to induce permeability of E. coli membranes is determined by an amphipathic helix formed at the N-terminus of 3A of HAVFG. PMID- 7794280 TI - Characterization of cDNA encoding novel pregnancy-specific glycoprotein variants. AB - The human pregnancy-specific glycoprotein (PSG) family consists of eleven closely related molecules mainly synthesized by placental syncytiotrophoblasts and whose function(s) are unknown. They belong to the carcinoembryonic antigen (CEA) family. As a step toward understanding PSG function, we have analysed 84 PSG cDNA clones from a fetal liver library with respect to domain arrangement and PSG identity. Four novel PSG cDNAs derived from the PSG4, PSG7, PSG11, and PSG13 genes were characterized. The PSG11 and PSG13 cDNAs had novel domain arrangements: L-N-B2-C (named type III) and L-A1-B2-C (named type IV), respectively. These splice variants were also demonstrated in placenta. PSG4 cDNA had a type IIa (L-N-A1-B2-C) and PSG7 cDNA a type I (L-N-A1-A2-B2-C) domain arrangement. PSG1, PSG4, PSG5 were found at highest frequency while PSG8 and PSG12 cDNA clones were not detected. PMID- 7794281 TI - Lovastatin inhibits proliferation and differentiation and causes apoptosis in lipopolysaccharide-stimulated murine B cells. AB - Lipopolysaccharide-stimulated murine B lymphocytes were incubated with the pharmacologic drug lovastatin, a competitive inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A reductase at concentrations ranging from 10(-5)-10(-8) M. After 48 hr, treatment with 10(-5)M lovastatin inhibited [3H]thymidine incorporation 55%. Flow cytometric analysis indicated that the fraction of B cells in S phase was reduced from 26.7% +/- 5.44% to 11.6% +/- 2.9% when cells were incubated with 10(-5)M lovastatin. In addition, a large peak appeared to the left of the G1 peak that was indicative of apoptosis in cells treated with 10( 5)M lovastatin. At 96 hr, the number of plaque-forming B cells was decreased 50% in the presence of lovastatin. Together these results suggest that high concentrations of lovastatin can inhibit B cell proliferation and differentiation of murine B lymphocytes in lipopolysaccharide-activated B cells, perhaps through induction of programmed cell death. PMID- 7794282 TI - Nitric oxide regulation of IL-8 expression in human endothelial cells. AB - The regulatory signals required to induce the production of IL-8, an important neutrophil chemoattractant and activator, have yet to be clearly defined. We examined the role of nitric oxide (NO) in IL-8 regulation. The NO synthase inhibitor, (L)-NG-nitroarginine methyl ester (L-NAME), inhibited the TNF stimulated IL-8 production in the human endothelial cell line, ECV304, in a dose dependent manner without affecting cellular viability (TNF alone, 5.5 +/- 0.9 ng/ml; TNF + 5 mM L-NAME, 2.4 +/- 0.5 ng/ml). Moreover, exogenously added NO produced by the spontaneous NO generating compounds, S-Nitroso-N-acetyl-D,L pennicillamine (SNAP) and Ethanamine, 2,2'-(hydroxynitrosohydrazono)bis- (DETA NONOate), induced a dose-dependent release of IL-8 from these cells. Maximal stimulation of IL-8 was found to be 1.2 +/- 0.1 ng/ml with the 1 mM concentration of SNAP and 1.6 +/- 0.1 ng/ml with the 2 mM concentration of DETA NONOate. These results provide key evidence substantiating a regulatory role of NO in IL-8 expression. PMID- 7794283 TI - Adrenocortical steroids, thyroid hormones and retinoic acid augment the production of adrenomedullin in vascular smooth muscle cells. AB - Adrenomedullin (AM) is produced and secreted from vascular smooth muscle cells (VSMCs), which express AM specific receptors. In the survey for substances regulating AM production, we found that dexamethasone, hydrocortisone and aldosterone stimulate AM production in cultured rat VSMC with ED50 values of 2.4 nM, 16 nM and 270 nM, while progesterone, estradiol and testosterone induced weak or no effect. Maximal stimulation levels of dexamethasone, hydrocortisone and aldosterone were comparable and a little lower than those of the most potent stimulants, interleukin-1 and tumor necrosis factor. Hydrocortisone dose dependently activated AM gene transcription, and AM mRNA level was highest at 12 h after stimulation. A physiological concentration of hydrocortisone was deduced to be enough to regulate AM production in VSMC. Retinoic acid and thyroid hormones increased AM production to 400% and 150% after 14 h incubation. These results demonstrate a complex regulation system of AM production in VSMC by hormones and related substances. Furthermore, effects of actinomycin D and cycloheximide suggest that biosynthesis of AM is designed for quick response to physiological stimulation. PMID- 7794284 TI - Human proadrenomedullin N-terminal 20 peptide in pheochromocytoma and normal adrenal medulla. AB - Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide found in adrenomedullin precursor. Using a radioimmunoassay for human PAMP, we purified immunoreactive PAMP (ir-PAMP) from human pheochromocytoma and determined its complete amino acid sequence. The major component of PAMP-like immunoreactivity was found to be PAMP [1-20] NH2 with an amino acid sequence identical to that of the deduced amino acid sequence by cDNA analysis. Both ir PAMP and ir-adrenomedullin were found to be abundant in normal adrenal medulla as well as pheochromocytoma tissue arising from adrenal medulla, and there was a significantly (p < 0.05) positive correlation between ir-adrenomedullin and ir PAMP concentrations in these tissues. However, the PAMP/adrenomedullin ratio in pheochromocytoma tissues (0.197 +/- 0.013) was significantly (p < 0.005) lower than that in adrenal medullae (0.384 +/- 0.041). The present data indicate that PAMP is biosynthesized from adrenomedullin precursor, but the biosynthesis or metabolism of PAMP in pheochromocytoma may be different from that of normal adrenal medulla. PMID- 7794286 TI - [Urinary tract infections]. PMID- 7794285 TI - Absence of the mitochondrial A7237T mutation in Parkinson's disease. AB - In recent years much has been speculated about a pathogenic role of mitochondrial defects in Parkinson's disease. Ozawa et al. (BBRC 176, 938-946, 1991) have described an A/T transversion at nucleotide 7237 of mitochondrial DNA affecting cytochrome-c-oxidase (complex IV) of the respiratory chain that could contribute to the pathogenesis of PD. Employing PCR based genomic sequencing and restriction enzyme analysis on 19 cases of Lewy-body parkinsonism, we exclude this mutation as a common cause of Parkinson's disease. This demonstrates the need for systematic sequencing of the mitochondrial genome in a large number of histologically verified cases of Parkinson's disease. PMID- 7794287 TI - Techniques of split-thickness skin grafting for lower extremity ulcerations. AB - OBJECTIVE: To discuss the role of skin grafts in the functional repair of lower extremity ulcerations. METHODS: The indications, types of skin grafts, and the methods of harvesting grafts are described. RESULTS: Detailed description of our method of bedside split-thickness skin grafting with both pinch and mesh grafts in hospitalized patients is given. We also discuss post-operative care and complications seen with skin grafting. CONCLUSION: Split-thickness skin grafting offers an important therapeutic option in the treatment of lower extremity ulcerations. PMID- 7794288 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part IV. Alcohol use. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for alcohol use are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. Of the sample, 53.2% reported ever using alcohol; 26.2% had used it recently and 15.4% reported episodes of binge drinking in the previous 14 days. Drinking patterns varied according to school standard, home language, and gender. Males reported higher rates of alcohol use and for both genders rates increased with age. Overall, the prevalence of drinking was highest among adolescents whose home language was English. The proportion of Xhosa-speaking females who drank was very low. The prevalence of binge drinking in particular was identified as being of concern. The findings indicate a need for preventive action and further local research in this area. PMID- 7794290 TI - Comparison of polymerase chain reaction tests and faecal culture for detecting Mycobacterium paratuberculosis in bovine faeces. AB - A polymerase chain reaction (PCR) test for M. paratuberculosis was developed based on a 218 bp segment of a DNA insertion sequence, IS900, that is specific for this organism. The method involved two consecutive amplification reactions, with the second set of primers being nested inside the first set. The method reliably detected 50 organisms/g faeces. This PCR test was applied to 32 bovine faecal specimens containing high, moderate or low numbers of M. paratuberculosis organisms as determined by culture. The PCR test detected all specimens containing > or = 1600 colony forming units (cfu)/g faeces, six of ten specimens with 160-480 cfu/g faeces but only two of 13 specimens containing < or = 112 cfu/g faeces. The sensitivity of this test was better than that of a commercial PCR test which was carried out on the same faecal specimens. PMID- 7794289 TI - A device for overcoming discoordination with metered-dose inhalers. AB - BACKGROUND: Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS: We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS: Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION: Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination. PMID- 7794291 TI - Intramucosal carcinoma developing in a hyperplastic gastric polyp. PMID- 7794292 TI - Divergent neuroprotective effects of nimodipine in PDD and MID provide indirect evidence of disturbances in Ca2+ homeostasis in dementia. AB - Evidence suggesting that increased cytotoxic Ca2+ concentrations due to disturbances of Ca2+ homeostasis are involved in neuronal deterioration in dementia has accumulated but has not yet been explicitly confirmed. Here we report of divergent neuroprotective effects of nimodipine, a Ca2+ channel blocker with high lipophilic properties, in primary degenerative dementia (PDD) and multiinfarct dementia (MID). Our clinical data show that nimodipine improves clinical symptomatology and cognitive functions in dementia significantly better than placebo but is more effective in PDD than in MID. This fact becomes explicitly apparent by comparison of the mean value differences of each of the 18 SCAG items between onset and termination of treatment in the two diagnostic groups. The divergent therapeutic response in PDD and MID suggests that the neuroprotective effects of nimodipine can not be due mainly to unspecific cognition enhancing mechanisms or vasodilatation of cerebral blood vessels but must primarily be the consequence of a direct activity in depolarized neuronal cells and of its ability to protect neuronal tissue from Ca2+ overload. Hence, we conclude that disturbances in Ca2+ homeostasis play an important role in the process of neuronal deterioration in dementia. Although we can not entirely rule out the possibility that pharmacological activities besides the modulation of neuronal Ca2+ influx contribute to the effects of nimodipine, from a clinical view our results provide indirect evidence of disturbances in Ca2+ homeostasis as one of the primary factors in the demential process. Our results further support the usefulness of nimodipine in the pharmacotherapy of age-related mental deficits. PMID- 7794293 TI - Cardiovascular research in the pharmaceutical industry: a personal appeal for rationalizing development. PMID- 7794294 TI - Test reliability is critically important to molecular epidemiology: an example from studies of human papillomavirus infection and cervical neoplasia. AB - To demonstrate that it is critically important to achieve excellent test reliability before conducting full-scale molecular epidemiological studies, data were compared from two consecutive case-control studies of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia. The major methodological difference between the two studies was the much greater reliability of the HPV test used in the second study. Although the first study used an assay considered state-of-the-art at that time, mediocre test reliability led to (a) a weakened association between HPV and risk of cervical intraepithelial neoplasia, (b) a weakened association between known risk factors for cervical intraepithelial neoplasia and HPV prevalence, (c) failure to demonstrate that HPV infection explains the known risk factors for cervical intraepithelial neoplasia, and (d) a marked reduction in the estimated proportion of cervical intraepithelial neoplasia attributable to HPV infection. With an improved assay, the second study strongly supported the idea that HPV infection is an intermediate end point explaining the known epidemiology of cervical intraepithelial neoplasia. Based on this experience and supportive theoretical considerations, we recommend that researchers optimize the reliability of innovative assays before application to full-scale molecular epidemiological projects. PMID- 7794295 TI - Kernicterus in a full term infant. PMID- 7794296 TI - Sodium arsenite induces heat shock protein-72 kilodalton expression in the lungs and protects rats against sepsis. AB - OBJECTIVE: To examine the hypothesis that induction of heat shock proteins by a nonthermal mechanism would confer protection against experimental sepsis. DESIGN: Prospective, blind, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Sixty-two adult male Sprague-Dawley rats (weight range 250 to 350 g). INTERVENTIONS: Administration of sodium arsenite or saline in an animal model of sepsis by cecal ligation and perforation. MEASUREMENTS AND MAIN RESULTS: Sixty-two rats were randomly divided into two groups: group 1 received sodium arsenite (6 mg/kg iv) and group 2 received saline injection, in a blinded fashion. Eighteen hours after receiving sodium arsenite or saline, cecal ligation and perforation were performed and the animals were monitored for mortality for 96 hrs. Sodium arsenite injection, in the absence of an increase in body temperature, induced heat shock protein of 72-kilodalton molecular weight expression in the lung, which was detected 2 hrs after injection, peaked between 9 and 24 hrs, and returned to baseline by 48 hrs. Prior administration of sodium arsenite conferred significant protection against cecal ligation and perforation induced mortality at 18 hrs (p = .002) and 24 hrs (p v .026) after cecal ligation and perforation, and correlated with expression of heat shock proteins in the lungs. However, at 48 and 96 hrs, when heat shock protein expression returned to basal values, the mortality rates of both groups were indistinguishable. CONCLUSIONS: We conclude that in vivo injection of sodium arsenite induces expression of HSP-72 in the lungs, and confers transient protection against experimental sepsis during the period that heat shock proteins are also expressed. PMID- 7794297 TI - Kidneys from pediatric donors: risk versus benefit. AB - We encountered four adult patients who received renal transplants from young children < 36 months of age, each of whom developed severe hypertension, heavy proteinuria, and progressive renal failure. Biopsies disclosed glomerular sclerosis with crescents in three patients and mesangial expansion in one. We thus analyzed our experience with 74 adults who received grafts from donors < or = 10 years of age and compared the results to those of 804 patients who were transplanted with kidneys from donors > 10 years of age. A Kaplan-Meier analysis revealed that graft survival was significantly worse in patients receiving grafts from younger, compared to older donors. This difference was apparent in patients treated either with or without cyclosporine. A subanalysis comparing patients with donor grafts aged < or = 5 or 6-10 years revealed a further adverse age related effect. Renal artery thrombosis and recurrent or de novo biopsy-proven glomerulonephritis were more common in patients receiving grafts from younger donors, while graft failure from rejection actually appeared less common. We conclude that severe hypertension and resultant glomerular hyperperfusion promoted glomerulosclerosis and crescent formation in our patients. Our results have caused us to pursue a more conservative approach towards transplanting grafts from donors aged < or = 10 years into adult recipients. PMID- 7794298 TI - Decisions about life-threatening risks. PMID- 7794299 TI - Recurrence of pemphigus vulgaris associated with interleukin 2 therapy. AB - BACKGROUND: Immunotherapy with recombinant interleukin 2 may result in regression of metastatic cancer, particularly malignant melanoma and renal cell carcinoma. OBSERVATIONS: We describe a patient who received interleukin 2 immunotherapy for metastatic renal cell carcinoma. After his second course of treatment, he developed a recurrence of pemphigus vulgaris that had been in remission for 10 years. CONCLUSIONS: Interleukin 2 therapy may be associated with recurrence of an autoimmune disease, perhaps because of its ability to stimulate autoantibody production. PMID- 7794300 TI - The contribution of dystocia to the cesarean section rate. AB - OBJECTIVE: Our purpose was to examine the indications for performing cesarean sections in current obstetric practice and to define and measure the true contribution of dystocia ("difficult labor") to the overall cesarean section rate. STUDY DESIGN: A prospective audit was done of all cesarean sections performed during 1991 at The Queen Mother's Hospital, Glasgow, a teaching hospital and tertiary referral center. RESULTS: The cesarean section rate for 1991 was 16.3%. Dystocia was the primary indication in 16% of all cesarean sections in 1991 but was actually a contributing factor, directly or indirectly, in the decision to operate in up to 38% of all cesarean sections that year. Seventy-eight percent of patients delivered because of dystocia were in spontaneous labor. We advocate more widespread use of a policy of active management in nulliparous women who labor spontaneously. If dystocia is addressed successfully, then many repeat cesarean sections may also be avoided. CONCLUSIONS: Improved management of dystocia in nulliparous women, such as the use of a policy of active management of labor, may be the most useful approach to reducing the cesarean section rate in modern obstetric practice. PMID- 7794301 TI - Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population. AB - The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women. PMID- 7794302 TI - Megestrol acetate in patients with AIDS-related cachexia. AB - OBJECTIVES: To compare the effects of oral suspensions of megestrol acetate, 800 mg/d, and placebo on body weight in patients with acquired immunodeficiency syndrome (AIDS)-related weight loss. DESIGN: Randomized, double-blind, placebo controlled trial. SETTING: Outpatient community and university patient care setting. PATIENTS: Consecutive patients with AIDS who had substantial weight loss and anorexia were enrolled. Of 271 patients, 270 and 195 were evaluable for safety and efficacy, respectively. INTERVENTIONS: Patients were randomly assigned to receive placebo or megestrol acetate (100 mg, 400 mg, or 800 mg) daily for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy criterion was weight gain. Patients were evaluated at 4-week intervals for changes in weight and body composition, caloric intake, sense of well-being, toxic effects, and appetite. RESULTS: For evaluable patients receiving 800 mg of megestrol acetate per day, 64.2% gained 2.27 kg (5 pounds) or more compared with 21.4% of patients receiving placebo (P < 0.001). An intent-to-treat analysis showed significant differences (P = 0.002) between those receiving placebo and those receiving 800 mg of megestrol acetate for the number of patients who gained 2.27 kg (5 pounds) or more (8 of 32 [25%] compared with 38 of 61 [62.3%], respectively). Compared with patients receiving placebo at the time of maximum weight change, evaluable patients receiving megestrol acetate, 800 mg/d, reported improvement in overall well-being and had an increase in mean weight gain (-0.725 compared with 3.54 kg [-1.6 compared with +7.8 pounds]; P < 0.001), lean body mass (-0.772 compared with +1.14 kg [-1.7 compared with +2.5 pounds]; P < 0.001), appetite grade (P < 0.001), and caloric intake (-107 compared with +645.6 calories/d; P = 0.001). CONCLUSIONS: In patients with AIDS-related weight loss, megestrol acetate can stimulate appetite, food intake, and statistically significant weight gain that is associated with a patient-reported improvement in an overall sense of well being. PMID- 7794304 TI - Endoscopic replacement of PEG. PMID- 7794303 TI - Comparison of biopsy sites for the histopathologic diagnosis of Helicobacter pylori: a topographic study of H. pylori density and distribution. AB - The histologic demonstration of characteristic curved, spiral bacilli on the gastric mucosa is considered the gold standard for the diagnosis of Helicobacter pylori infection. However, in some cases the urea breath test or serologic tests may be positive, yet gastric biopsy specimens fail to reveal H. pylori. The objectives of this study were (1) to analyze the density and distribution of H. pylori in different regions of the stomach, (2) to ascertain which area of the stomach is a preferential site for obtaining biopsy specimens, and (3) to determine whether the presence of neutrophils or lymphoid aggregates correlates with the presence of detectable organisms in the same biopsy specimen. Eighty nine patients with H. pylori infection underwent gastric mapping. The density of H. pylori, neutrophils, and lymphoid follicles was assessed semi-quantitatively in each biopsy site. The likelihood of getting a false-negative result was also calculated for each biopsy site. All biopsy specimens from the antral lesser curvature, at or near the incisura, had detectable H. pylori. Scores for this area and the cardia were higher than scores for the gastric corpus, but most differences were not significant. Fewer than 3% of antral biopsy specimens were false-negative, compared to between 6% and 9% of those from the corpus (p = 0.02). Neutrophils were present in more than 94% of all antral biopsy specimens, compared to 60% to 86% of specimens from the corpus (p < 0.01). Lymphoid follicles were detected in approximately two-thirds of antral biopsy specimens but in fewer than half of those from the corpus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794305 TI - An audit of the treatment of cancer of the oesophagus. AB - The treatment of cancer of the oesophagus in The General Infirmary at Leeds between the years 1975 and 1988 was reviewed. All cases with histologically proved cancer of the oesophagus were included, data being obtained from case notes, theatre operation books, endoscopy records, pathology records, and the Yorkshire Cancer Registry. Three hundred and sixteen patients were identified. Demographic details, mode of presentation, preoperative investigations, surgical management, methods of palliation, and survival data were entered into a database. The male to female ratio was 3:2 and the median age at presentation was 69 years (range 35-96). Surgical exploration was carried out in 134 of 316 patients (42%). Resection of the tumour, whether curative or palliative, was possible in 106 of 134 patients (79%). Operative (30 day) mortality was 27%. In 22 of 134 patients (16%), only intubation of the tumour was possible, while six patients (5%) had a thoracotomy or laparotomy alone. Median survival of the 106 patients after surgical resection was 292 days (range 0-14.2 years) and seven of them (7%) were still alive five years later. Of the remaining 182 patients (58%) who were not operated upon, 36 patients (11%) had a radical course of radiotherapy with a median survival of 175 days (range 80-453) and 146 patients (46%) either had endoscopic intubation (n = 64) or received no specific treatment (n = 82) with a median survival of 106 days (1-725) and 91 days (1-358) respectively. None of the 182 patients who did not have surgical treatment was alive at five years. PMID- 7794306 TI - Detection of the BC 24 transforming fragment of the herpes simplex virus type 2 (HSV-2) DNA in cervical carcinoma tissue by polymerase chain reaction (PCR). AB - The polymerase chain reaction (PCR) was used to investigate samples from Indonesian and Swedish patients with cervical intraepithelial neoplasia grade III (CIN III), squamous cell carcinoma or adenocarcinoma of the cervix for the presence of a transforming fragment (BC 24) of herpes simplex virus type 2 (HSV 2) DNA. The PCR test for HSV-2 DNA was more sensitive than the infectivity endpoint titer in a cell culture system and no cross reactivity was found with either varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human papillomavirus 16 or 18, or human genomic DNA. Using this PCR test, 2 out of 5 cases with CIN III, 10 of 71 squamous cell carcinomas, and 3 of 11 adenocarcinomas of the uterine cervix were found to contain DNA sequences homologous to the BC 24 fragment of the HSV-2 genome. Only two of the samples containing this transforming region of the HSV-2 DNA were positive in a PCR assay for the HSV-2 DNA polymerase gene. The great majority of the HSV-2 BC 24 DNA positive (12 of 15) came from the Indonesian group of patients. All 15 CIN III or cancer samples positive for the HSV-2 BC 24 fragment were also positive for papillomavirus DNA. In line with observations made by others, our data support the hypothesis that HSV infection could represent one of several possible oncogenic cofactors leading to cervical carcinoma. The HSV cofactor might be more important in the Indonesian than in the Swedish population. PMID- 7794307 TI - A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematological or oncological malignancies. Multicentre Study Group. AB - A randomized, comparative study was conducted in 502 patients in 23 centres world wide to assess the efficacy and safety of fluconazole versus nystatin and amphotericin B for prevention of fungal infection in a severely immunocompromised pediatric population. Patients scheduled within 48 hours to undergo chemotherapy or radiotherapy for hematological or oncological malignancies were randomly allocated to receive 3 mg/kg oral fluconazole once daily, 50,000 U/kg oral nystatin four times daily or 25 mg/kg oral amphotericin B four times daily. Prophylaxis began with the initiation of chemotherapy or radiotherapy and continued throughout a patient's hospital stay or period of neutropenia as necessary. The mean duration of fluconazole prophylaxis was 27.8 days and of the oral polyenes 29.2 days. The outcome of prophylaxis with fluconazole was significantly superior to that with the polyenes (p = 0.01). Mycologically verified infections occurred in 5 patients (2.1%) given fluconazole and in 21 (8.4%) given polyenes (p = 0.002). Clinical evaluation at the end of prophylaxis showed that the clinical outcome was definitely or possibly successful in 87% in the fluconazole group and 82% in the polyenes group with no significant differences between the treatment groups. Mycological evaluation demonstrated reduction or control of colonization in 84% in the fluconazole group and 85% in the polyenes group, again with no significant between-group differences. Possibly drug-related side effects, mainly mild to moderate gastrointestinal disturbances, were reported in 38 patients given fluconazole, with eight subsequent withdrawals, and in 21 patients given oral polyenes, with three subsequent withdrawals. Laboratory test abnormalities occurred in 28 patients given fluconazole and 24 given polyenes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794308 TI - Association of moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator. AB - OBJECTIVE: To assess whether an association exists between moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator (t-PA), a serine protease that plays a central role in the regulation of intravascular fibrinolysis. DESIGN: Survey of self-reported alcohol consumption and plasma fibrinolytic capacity, controlled for lipid and nonlipid cardiac risk factors. SETTING: Participants in the Physicians' Health Study. PARTICIPANTS: A total of 631 apparently healthy male physicians aged 40 to 84 years with no history of myocardial infarction, stroke, or transient cerebral ischemia. MAIN OUTCOME MEASURE: Plasma concentration of t-PA antigen. RESULTS: A direct association was found between alcohol consumption and plasma level of t-PA antigen, such that mean plasma levels of t-PA antigen for daily, weekly, monthly, and rare or never drinkers were 10.9, 9.7, 9.1, and 8.1 ng/mL, respectively (P trend = .0002). The relation between alcohol consumption and t-PA antigen level was not materially changed in analyses that adjusted for total cholesterol and high-density lipoprotein cholesterol or nonlipid cardiovascular risk factors including age, body mass index, parental history of coronary heart disease, exercise frequency, and systolic and diastolic blood pressure. CONCLUSIONS: These data indicate a positive association between moderate alcohol intake and plasma level of endogenous t-PA antigen that is independent of high-density lipoprotein cholesterol. This finding supports the hypothesis that changes in fibrinolytic potential may be an important mechanism whereby moderate alcohol consumption decreases risk of heart disease. PMID- 7794309 TI - What to advise patients about drinking alcohol. The clinician's conundrum. PMID- 7794310 TI - Severe adverse cutaneous reactions to drugs. PMID- 7794311 TI - Neurologic manifestations of HIV infection. AB - PURPOSE: To review the clinical features, pathogenetic mechanisms, and management of neurologic manifestations of human immunodeficiency virus (HIV) infection. DATA SOURCES: Studies published from 1983 to 1994 identified by MEDLINE literature search; Centers for Disease Control and Prevention reports; recent communications and abstracts; and authors' published and unpublished data. STUDY SELECTION: We selected studies that described the clinical characteristics of neurologic disorders in the acquired immunodeficiency syndrome (AIDS), basic science studies addressing the mechanisms of direct or indirect neurologic damage in HIV infection, and clinical trials investigating the effects of therapeutic agents on the neurologic complications of AIDS. DATA EXTRACTION: We evaluated information and data on epidemiologic characteristics, clinical manifestations, pathogenetic mechanisms, and therapy for neurologic complications of HIV disease and outlined a practical approach to assess and manage these disorders. DATA SYNTHESIS: In the past decade, basic and clinical studies have provided considerable information about neurologic manifestations of AIDS. Dementia is the most important "primary" neurologic complication of HIV infection. Focal lesions of the central nervous system include cerebral toxoplasmosis, lymphoma, and progressive multifocal leukoencephalopathy. Other opportunistic infections include cytomegalovirus encephalitis, cryptococcal meningitis, and neurosyphilis. Various peripheral neuropathies and myopathies may occur in association with HIV infection or as toxic effects of antiretroviral agents. CONCLUSIONS: The prevalence of neurologic complications associated with HIV disease will increase as more effective therapies allow persons with AIDS to live longer. Early recognition and treatment of these disorders substantially affect patients' quality of life and survival. PMID- 7794312 TI - Case report: a gastroduodenal artery pseudoaneurysm presenting with obstructive jaundice and treated by arterial embolization. AB - A case of obstructive jaundice due to a pseudoaneurysm of the gastroduodenal artery is reported. This was successfully embolized, with relief of the jaundice. Relief of biliary obstruction by aneurysm embolization has not, to our knowledge, been previously described. PMID- 7794313 TI - Cosmetic breast fibrosis: it's the local boost! PMID- 7794316 TI - Euthanasia and physician-assisted suicide. PMID- 7794315 TI - A comparison of stress in surgically and non-surgically mulesed sheep. AB - A comparison has been made in 9- to 10-month-old castrated male Merino sheep of the changes in plasma total cortisol concentration and behaviour after being treated by either the modified Mules operation or by topical application of a quaternary ammonium compound to achieve non-surgical mulesing. After surgical mulesing, plasma total cortisol concentration increased immediately and rapidly and reached a peak value in 15 minutes, whereas after non-surgical treatment an immediate rise did not occur, but a similar peak value was observed in blood samples collected 24 hours after treatment. The concentrations were lower in both groups at 48 hours. Likewise postural changes indicative of discomfort were immediately apparent in the surgically treated sheep, but not until 3 to 4 hours later in those treated non-surgically. Arena testing revealed that a lasting aversion to the person who restrained them during treatment developed in the surgically mulesed sheep, but not in those treated non-surgically. The non surgical procedure did not create large open wounds, as did the surgical operation, but still achieved similar enlargement of the bare area on the breech, and healing was quicker in the non-surgically treated sheep. PMID- 7794314 TI - Exercise tomographic thallium-201 imaging in patients with severe coronary artery disease and normal electrocardiograms. AB - OBJECTIVE: To assess the incremental value and cost-effectiveness of exercise tomographic thallium-201 imaging compared with clinical and exercise electrocardiographic variables for detecting three-vessel or left main coronary artery disease in patients with normal at-rest electrocardiograms. DESIGN: Prospective cohort study. PARTICIPANTS: 411 patients (77 [19%] had three-vessel or left main disease) with normal at-rest electrocardiograms who underwent exercise tomographic thallium-201 studies and subsequently had coronary angiography. MEASUREMENTS: Clinical, exercise, and thallium-201 variables; univariate followed by multivariate logistic regression analysis to determine predictors of three-vessel or left main disease (clinical variables; clinical and exercise electrocardiographic variables; and clinical, exercise, and thallium-201 variables). Patients were classified by each of these models into low-, intermediate-, and high-risk groups. SETTING: A tertiary referral center. RESULTS: Among the clinical variables, diabetes mellitus, sex, age, and typical angina were independently associated with severe coronary disease (46% of patients were correctly classified into low- or high-risk groups). The peak exercise heart rate-blood pressure product and the magnitude of the exercise induced ST depression added independent information to clinical variables. Among the thallium variables, the change in the global thallium-201 score (a measure of redistribution) added independent information to clinical and exercise variables, resulting in only 3% of the patients being reclassified regarding their predicted risk for severe coronary disease. The cost per additional reclassification was estimated to be $20,550. Twenty-one cardiac events occurred (7 cardiac deaths and 14 myocardial infarctions) after thallium study (follow-up, 2.8 +/- 1.0 years). Event-free survival was 94% to 97% regardless of the predicted probability of developing three-vessel or left main coronary artery disease by any model. CONCLUSIONS: When the at-rest electrocardiogram is normal, thallium-201 scintigraphy adds little information to clinical and exercise variables in identifying patients with severe coronary artery disease. The high cost of this information may not justify the routine use of sophisticated imaging for this purpose. PMID- 7794317 TI - Five-year follow-up of mandibular reconstruction with hydroxylapatite and the mandibular staple bone plate. AB - PURPOSE: To evaluate the results of hydroxylapatite augmentation of the mandible followed by placement of the mandibular staple. PATIENTS AND METHODS: Sixty patients 5 or more years postsurgery were evaluated. Patients were followed yearly with clinical and radiographic examinations. RESULTS: The decrease in augmentation height was 2.8 mm (33%) after the first year and only minimal in the following years. The following problems were seen: hyperplastic tissue around posts (eight patients), small dehiscences were seen in the saddle area after 2 years (11 patients), large dehiscences with significant hydroxylapatite loss in five patients. One patient needed a secondary augmentation. CONCLUSION: Prosthetic stabilization and function were excellent throughout the study period and there was a uniformly high degree of patient satisfaction. PMID- 7794318 TI - Comparison of the proteins in salivary glands, saliva and haemolymph of Rhipicephalus appendiculatus female ticks during feeding. AB - To compare the proteins in salivary glands, saliva and haemolymph of Rhipicephalus appendiculatus female ticks, antisera were prepared from guinea pigs immunized with soluble denatured salivary gland extracts (SGE). The extracts were derived from R. appendiculatus female ticks that were either unfed (day 0) or partly fed (day 6). The sera were used in immunoblotting, following SDS polyacrylamide gel electrophoresis, to examine the antigen profiles during the course of tick feeding on guinea-pigs. Day 0 and day 6 SGE antisera appeared to detect common proteins in the different tick samples. For example, haemolymph apparently shared some of the small protein bands (31.5-34 kDa) detected in SGEs. These small proteins appeared in both samples at the same stage of feeding, suggesting that haemolymph and salivary glands not only have common antigens but may also share some functions. Furthermore, a number of protein bands were detected in haemolymph before they were apparent in the salivary glands or saliva. Thus some antigens detected in the salivary glands and saliva may be derived from the haemolymph. The results indicate that the host may be exposed to tick saliva antigens that are also present in the haemolymph. We discuss the significance of these observations with regard to the induction of host immunity to ticks and the development of tick vaccines. PMID- 7794319 TI - Excretion of host immunoglobulin in tick saliva and detection of IgG-binding proteins in tick haemolymph and salivary glands. AB - Host immunoglobulin G (IgG) crossed the gut wall into the haemocoel of adult Rhipicephalus appendiculatus female ticks when they fed on guinea-pigs. Guinea pig IgG was also found in saliva of the feeding ticks. The concentration and antibody activity of IgG in haemolymph, salivary gland extract (SGE) and saliva at different stages of tick feeding were detected by enzyme-linked immunoassay. Specific activity of the IgG in tick samples was determined by feeding ticks on guinea-pigs which were immunized with killed Escherichia coli: 35-42% of the antibody activity in guinea-pig immune serum remained in the tick samples. The high relative concentration of IgG in tick saliva at later stages of feeding suggests that the tick may have a mechanism for getting rid of foreign proteins via the salivary gland. Such a mechanism could involve IgG binding proteins (IGBPs) which were found in both haemolymph and SGE of female ticks at day 6 of feeding using a guinea-pig IgG-agarose affinity column. In female ticks, the M(r) of IGBPs in SGE (23 and 57 kDa) were less than those in haemolymph (78 and > 100 kDa). The existence of IGBPs in both the tick salivary gland and haemolymph indicate that haemolymph and salivary gland cooperate to remove foreign proteins, e.g. host immunoglobulin, from the body during feeding. This mechanism may be a part of the tick self-defence system. PMID- 7794321 TI - Auramine fluorescence for acid-fast bacilli in formalin-fixed paraffin-embedded tissues. PMID- 7794320 TI - The CR-CO discrepancy and its effect on cephalometric measurements. AB - The purpose of the present study was to compare cephalometric measurements derived from a centric occlusion (CO) tracing with those of a converted centric relation (CR) tracing. The sample consisted of 68 consecutively treated patients, with a CR-CO discrepancy of 2 mm or greater in either the horizontal and/or vertical planes, measured at the condyles from mounted models. Comparisons were also made within the sample between the 39 females and 29 males; and the 35 skeletal Class I and 33 Class II patients. In analyzing the CR-CO discrepancy, the vertical component was greater than the horizontal in 96% of the sample. Every patient had a vertical component, although 10% had no horizontal component. Correlations between the horizontal discrepancy and the two tracings showed high values for approximately 50% of the measures, whereas little correlation was found with the vertical discrepancy. Paired t tests used to compare the CO and CR cephalometric values demonstrated significant differences (p < 0.05) for the majority of the values studied. However, there generally were no differences between the groups of males and females, or between the skeletal Class I and Class II individuals. The results of this study suggest that to make a correct orthodontic diagnosis the mandible should be placed in centric relation rather than in the more traditional centric occlusion. PMID- 7794322 TI - Possible coumarin hepatotoxicity. PMID- 7794323 TI - Upper gastrointestinal tract. AB - Drug therapy for upper gastrointestinal disease in the elderly must be moderated by the likelihood of increased sensitivity to the side effects of drugs. For example, in the frail elderly with helicobacter-associated duodenal ulcers, maintenance therapy with an H2-receptor antagonist or omeprazole may be preferable to attempting to eradicate Helicobacter pylori with the current antimicrobial regimens. PMID- 7794325 TI - Divisions of general practice: too much too quickly. PMID- 7794324 TI - Chiropractic and the politics of health care. AB - Musculoskeletal disorders remain a common disability suffered by Australians, but the question of who should treat them remains a contentious issue as the first centenary of the original chiropractic adjustment approaches. This paper, part of a longitudinal study of the role of chiropractic in the Australian health system, analyses this ongoing debate. Recent events are analysed here in this commentary on the politics of health care in this field. These include meta-analysis to evaluate the effectiveness of spinal manipulation for the treatment of lower back pain, recent legal action in the United States, and the recent epistle against Australian chiropractors published by the Australian Medical Association. PMID- 7794326 TI - Drug resistant tuberculosis. PMID- 7794327 TI - Prevalence of Asperger's syndrome in a secure hospital. AB - BACKGROUND: The hypothesis that Asperger's syndrome (AS) may go unrecognised in forensic populations was examined by ascertaining the prevalence in Broadmoor Special Hospital. METHOD: The entire male patient population was screened by examination of case notes. Identified cases were subject to the next stage of the study, which involved observation and interviewing of patients, and a semi structured interview of key staff. RESULTS: A prevalence of 1.5% (0.6% to 3.3%, 95% CI) was found. The addition of equivocal cases increased the prevalence to 2.3%. CONCLUSION: The prevalence of AS in Broadmoor Hospital is greater than that reported for the general population. PMID- 7794328 TI - Lymphoma of the mucosa-associated lymphoid tissue of the lung. A multifocal case of common clonal origin. AB - Low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) are extranodal tumors that tend to be localized. In this case report, the authors describe an unusual multifocal pulmonary MALT lymphoma, which presented radiologically as three discrete lesions involving two separate lobes of the lung, in addition to numerous separate macroscopic and microscopic foci of disease. The lesions were composed of centrocyte-like cells and cytologically bland plasma cells surrounding reactive lymphoid follicles with focal areas resembling lymphoid interstitial pneumonia (LIP). Immunohistochemical studies demonstrated a predominance of immunoglobulin kappa light chain positive plasma cells in the largest lesion. A polymerase chain reaction (PCR) assay demonstrated conserved immunoglobulin heavy chain gene rearrangements in the large tumor nodules as well as microscopic foci resembling LIP. This case illustrates the utility of PCR for identifying the clonal nature of lymphoid lesions that are too small or heterogeneous to unequivocally assess by other means. PMID- 7794329 TI - Comparison of standardized echography with magnetic resonance imaging to measure extraocular muscle size. PMID- 7794330 TI - Failure of consultant expansion. "Subconsultant" posts are increasing dramatically. PMID- 7794331 TI - The perils of Prozac. AB - In seven years, Prozac has become a social phenomenon as well as a medical treatment. This paper reviews the background of the Prozac controversy and summarizes the current psychiatric and medical uses of the drug. Prozac and the other selective serotonin re-uptake inhibitors have been determined to be safe and effective treatment for depression. Physicians are sometimes asked to prescribe the drug for inconsequential reasons, but serious depressions are seen frequently in general medical practice. Physicians thus need a high level of awareness and the capability to treat depression, a major public health problem. PMID- 7794332 TI - p53 and bladder cancer. PMID- 7794333 TI - Severe adverse cutaneous reactions to drugs. PMID- 7794334 TI - Which research results should the public believe? PMID- 7794335 TI - Oncogenes and cancer. PMID- 7794336 TI - Invasion of the cabbage patch. PMID- 7794337 TI - Prostate cancer kills. PMID- 7794338 TI - Comment on rapid molar distalization. PMID- 7794339 TI - Re: "Greater case-fatality after myocardial infarction among Mexican Americans and women than among non-Hispanic whites and men: The Corpus Christi Heart Project". PMID- 7794340 TI - Leprosy. Report of a Meeting of Physicians and Scientists at the All India Institute of Medical Sciences, New Delhi. PMID- 7794341 TI - Drug promotion. PMID- 7794342 TI - Accidental hypothermia. PMID- 7794343 TI - Medical savings accounts. Finally, a reform concept with integrity. PMID- 7794344 TI - Isolation of a parapoxvirus from pox-like lesions in grey seals. PMID- 7794345 TI - [Intestinal parasitoses in the prison population in the Madrid area (1991-1993)]. AB - BACKGROUND: Intestinal parasitoses are frequent in populations in tropical and subtropical areas, HIV infection has favoured an increase in the prevalence of some of these parasitoses . Both conditions concur in innate populations. The aim of this study was to determine the prevalence and clinical characteristics of the intestinal parasitosis in a penitentiary population from the Madrid area. METHODS: On the basis of the data from the Laboratory of Clinical Microbiology in the Hospital General Penitenciario, patients with the diagnosis of intestinal parasitosis were retrospectively reviewed. The study period covered 29 months (from 1/8/91 to 31/12/93). Samples were taken from patients admitted to, and attended, in the outpatient area of this hospital in addition to those held in dependents prisons. Processing was done by direct macroscopic and microscopic visualization (400x) of the sediment obtained by the formol-ether concentration method (Ritchie). Modified Ziehl staining was carried out. Demographic, clinical evolutive and microbiologic data of the patients were analyzed. RESULTS: One thousand two hundred eighty-one samples corresponding to 1,033 patients were studied 131 (10.2%) positives corresponding to 96 (9.3%) patients were observed. 88.5% (n = 85) were males. The mean age was 31.2 years (CI 95%: 29.3-32.9). The patients were from Europe in 39.7% of the cases (Spain: 94%), Africa 28.9% and Latin America 28.9%. Twenty-five patients were HIV+ (46%) with a mean CD4 count of 160/mm3 (CI 95%: 65-255) and 29 were HIV-. Globally, the most frequently found parasites were uncinaria (22%), Giardia lamblia (21%) and Cryptosporidium parvum (20%). One case of intestinal capillariasis was diagnosed. Fifteen mixed parasitoses (15.6%) were observed and the most frequent association was Trichuris trichiura and uncinaria in 8 patients (5 HIV+ and 3 unknown HIV). Clinical manifestations were present in 63.7% (42/66) of the patients with diarrhea being the most frequent (25 cases). In patients in whom the clinical evolution could be evaluated, it was favorable in most of the cases except in those with Cryptosporidium parasitosis. CONCLUSIONS: Intestinal parasites are of relevance within a prison population, presenting some differences to the intestinal parasites observed in a general population. The most frequently observed parasite was uncinaria in HIV- patients and Cryptosporidium parvum in HIV+ patients. Mixed parasitosis was not infrequent (15.6%). 25% of the intestinal parasitosis are asymptomatic. When symptomatology does exist, diarrhea is the most common clinical manifestation. The clinical evolution is usually favourable with the exception of some cases of diarrhea by Cryptosporidium in severely immunosuppressed HIV+ patients. PMID- 7794346 TI - Treating mental health problems of health care workers. PMID- 7794347 TI - Effects of oral pentoxifylline on TNF-alpha levels, transplant-related toxicities and engraftment after bone marrow transplantation. PMID- 7794348 TI - "One patient's experience with pancuronium bromide". PMID- 7794349 TI - Transmission of HIV. PMID- 7794350 TI - Epistaxis due to hereditary hemorrhagic telangiectasia. PMID- 7794351 TI - Upper gastrointestinal tract. PMID- 7794352 TI - Discussion of "Did the 65 mph speed limit save lives?". PMID- 7794353 TI - Haemodynamic effects of subarachnoid block in the elderly. PMID- 7794354 TI - Phospholipid binding antibodies warrant continued investigation. PMID- 7794355 TI - A fundamental problem of consent. Patients' trust must be respected. PMID- 7794356 TI - A fundamental problem of consent. Chaperones are necessary for female patients. PMID- 7794357 TI - A fundamental problem of consent. Information on anaesthesia for caesarean section is tailored to the woman. PMID- 7794358 TI - Asthma care in general practice. PMID- 7794359 TI - Cardiac troponin-T and diagnostic test evaluation. PMID- 7794360 TI - Omitting side holes in biliary stents. PMID- 7794361 TI - Paradoxical reactions to diazepam. PMID- 7794363 TI - Reinterpreting mortality statistics. PMID- 7794362 TI - Therapeutic approach to microvascular angina (syndrome X) PMID- 7794364 TI - Alcohol consumption and tissue-type plasminogen activator. PMID- 7794365 TI - Management of first-trimester spontaneous abortion. PMID- 7794367 TI - Kernicterus in a full-term infant: the need for increased vigilance. PMID- 7794366 TI - Immunologic defects of the peritoneum determine the bacteriology of peritonitis. PMID- 7794368 TI - Late-onset psychosis with somatic delusions. PMID- 7794370 TI - Congestive heart failure associated with endoscopic cholecystectomy. PMID- 7794369 TI - Adverse effects of topical corticosteroid use. AB - Topical corticosteroid use, a common and often efficacious therapy for a wide variety of cutaneous conditions, may have substantial adverse effects. These range from the notable nondermatologic side effects of hypothalamic-pituitary adrenal axis suppression, Cushing's disease, femoral head osteonecrosis, and cataracts to a variety of less serious skin effects such as cutaneous tinea and contact dermatitis. The broad availability, efficacy, relative low cost, and ease of applying topical corticosteroids should not induce complacency or a cavalier attitude in prescribers. Physicians should have the same awareness of the possible side effects of topical steroid use as when prescribing parenteral medication. PMID- 7794371 TI - Don't upset my equilibrium again! PMID- 7794372 TI - Spurious data collection misleads authors. PMID- 7794373 TI - Group B streptococcal prophylaxis randomized trials. PMID- 7794374 TI - Treatment of schizophrenia with anticholinergic medications. PMID- 7794375 TI - Elective lymph node dissection (ELND) for malignant melanoma. PMID- 7794376 TI - The role of Chlamydia trachomatis in urethritis and urethral symptoms in women. AB - One hundred and fifty women who attended a genitourinary medicine clinic and who required a speculum examination were investigated to determine the association between Chlamydia trachomatis and urethral symptoms and signs. Those who had taken antibiotics with anti-chlamydial activity within 3 months or those who were menstruating, pregnant or using an intrauterine contraceptive device were excluded. C. trachomatis infection of the urethra, or infection of the urethra and cervix together, combined with each separately, were strongly associated with > = 5 polymorphonuclear (PMN) leucocytes per high-power field (x 1000) in a Gram stained urethral smear (P < 0.00005 and P < 0.0005, respectively). This appeared not to arise from leucocyte contamination from the lower genital tract. However, C. trachomatis infection of the urethra was not associated with symptoms of dysuria or frequency. In conclusion, it seems likely that C. trachomatis infection of the urethra in women probably causes urethritis which is usually asymptomatic. Women who have objective evidence of urethritis might best be managed by appropriate antibiotic therapy and counselling, and advice that partners should attend for review. PMID- 7794377 TI - Screening for breast cancer. Diagnostic performance of radiographers can be improved. PMID- 7794378 TI - Screening for the breast cancer. Two views mean twice the dose of radiation. PMID- 7794379 TI - United Kingdom prospective diabetes study. Compliance with diet will affect results. PMID- 7794380 TI - Services for cleft lip and palate. Plastic surgeons support centralisation of services. PMID- 7794381 TI - Non-insulin dependent diabetes mellitus and non-Hodgkin's lymphoma. Already reported. PMID- 7794382 TI - Lithium in steroid-induced depression. PMID- 7794384 TI - MD or MRCP? A dilemma for the Sri Lankan physician. PMID- 7794383 TI - Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl-deficient rats. AB - Male weanling Fischer 344 rats were fed either a semipurified diet deficient in the methyl donors methionine, choline, and folic acid or a supplemented control diet for a period of 9 weeks. At intervals of 2, 5, and 7 days, 3 weeks, and 9 weeks after initiation of the respective diets, the relative level of DNA strand breaks and the degree of cytosine methylation were quantified in high molecular weight DNA and also within the p53 gene in liver samples from these rats. Genome wide strand break accumulation was associated with progressive genomic hypomethylation and increased DNA methyltransferase activity. With the use of quantitative PCR as a gene-specific DNA strand break assay, unique DNA strand breaks were detected in exon 5 but not in exons 6-8 of the p53 gene, and were accompanied by significant p53 gene hypomethylation. DNA hypomethylation has been shown to alter the conformation and stability of the chromatin structure, rendering affected regions more accessible to DNA-damaging agents. To determine whether methylation status alters the sensitivity of DNA to strand breakage, DNA in isolated nuclei was methylated in vitro and exposed to endogenous calcium/magnesium-dependent endonuclease activated under defined conditions. The incidence of enzyme-induced DNA strand breaks was decreased significantly with increased DNA methylation. In nuclei isolated from livers of methyl-deficient rats, the hypomethylated DNA was found to be more sensitive to enzyme- and oxidant-induced DNA strand break induction. Taken together, these results provide evidence that DNA strand breaks are induced in high molecular weight DNA and also within the p53 gene in liver tissue from methyl-deficient rats. The increased incidence of these strand breaks in DNA from methyl-deficient rats may be related to alterations in chromatin accessibility associated with DNA hypomethylation. PMID- 7794385 TI - Iron deficiency anaemia. PMID- 7794386 TI - Mitochondrial gene mutation as a cause of insulin resistance. PMID- 7794387 TI - The timeliness of new drug approvals in Canada. AB - In a recent article, Lexchin asks "who needs faster drug approval times in Canada?" and, on the basis of extremely limited and selective data, draws the conclusion that neither the public nor the pharmaceutical industry does. Whether the Canadian system is really slower is investigated by comparing Canadian and U.S. marketing approval dates and by using information on regulatory approval times from the two countries and elsewhere. Marketing approval dates in Canada are significantly later than those in the United States, although not consistently across all therapeutic categories; anti-cancer and gastrointestinal drugs have earlier approval dates in Canada. However, Canadian and U.S. regulatory approval times are not significantly different, indicating that marketing applications are submitted later in Canada, but both are considerably longer than those in the United Kingdom. The evidence shows that Canadians need faster drug approval times if individuals requiring the medications are not to suffer unnecessarily. A significant decrease in drug approval times and the establishment of comprehensive and effective postmarketing surveillance would reduce the time it takes for new drugs to be made available to Canadians while, at the same time, providing a high level of drug safety. PMID- 7794388 TI - Hematologic characteristics of greyhounds. PMID- 7794389 TI - The L-arginine:nitric oxide pathway is the major source of plasma nitrite in fasted humans. AB - 15N guanidino-labelled L-arginine was infused into fasted human volunteers giving, at equilibrium, a stable 1:10 ratio of 15N to 14N arginine in the plasma. Separate GC-MS assays were used to compare the degree of enrichment of plasma arginine, nitrite and nitrate and thus define the quantitative relationship between the L-arginine:nitric oxide (NO) pathway and the formation of these oxides of nitrogen. 15N nitrite enrichments rose to 8.3% (SD 0.5), five hours after the start of the infusion. In contrast, 15N nitrate enrichments apparently rose to only 1.6% (SD 0.4) at this time. This discrepancy could be explained by our finding that the commonly used Tesch GC-MS nitrate assay is subject to considerable interference from non-nitrate sources in plasma. Taking this into account, nitrate enrichments were similar to those observed for plasma nitrite. These results therefore indicate that the measurement of these compounds in plasma is a valid indicator of NO generation in fasted humans. PMID- 7794390 TI - Early days of Australian chiropractic. PMID- 7794391 TI - Wise words of Malleson accordant. PMID- 7794393 TI - One of the aims of interventional laparoscopy is anchored in aesthetics. PMID- 7794392 TI - Nitrous oxide has a very low abuse potential. PMID- 7794394 TI - Treatment of epiglottitis. PMID- 7794395 TI - Prenatal care key to breast-feeding. PMID- 7794396 TI - Post-streptococcal glomerulonephritis. PMID- 7794397 TI - Classification and diagnosis of erythromelalgia. PMID- 7794398 TI - Eyelid opening apraxia in focal cortical degeneration. PMID- 7794400 TI - Psychoanalysis: waning or waxing? PMID- 7794399 TI - The Barthel index in clinical practice. PMID- 7794401 TI - Core services and cardiac surgery. PMID- 7794402 TI - Consent to HIV testing. PMID- 7794403 TI - Alternative medicine. PMID- 7794404 TI - Screening for cervical cancer. PMID- 7794405 TI - Emergency medicine in South Africa. PMID- 7794406 TI - Classification of neuroendocrine carcinomas of the gastrointestinal tract. PMID- 7794407 TI - Megestrol for AIDS-related anorexia. PMID- 7794408 TI - Ready! Aim! Check the literature! PMID- 7794409 TI - Autoimmune disorders and interleukin-2 therapy: a step toward 'unanswered questions'. PMID- 7794410 TI - Plagiarism suit wins; experts hope it won't set a trend. PMID- 7794411 TI - Habits of death. Cultural variation in attitudes toward death. PMID- 7794413 TI - [Studies on the triterpenes from Bemeuxia thibetica Decne]. AB - Four triterpenes were isolated from the alcoholic extract of Bemeuxia thibetica Decne. A new triterpene, 16 alpha, 21 beta, 22 alpha, 28-tetrahydroxyolean-12-en 3-one, named bemeuxin (I), was identified on the basis of spectral evidences. The other three triterpenes were identified as 21-tigloylbarringtogenol C(II), 2 alpha, 3 alpha-dihydroxyursolic acid (III) and 2 alpha, 3 beta-dihydroxyursolic acid (IV). PMID- 7794412 TI - An ICAM-related neuronal glycoprotein, telencephalin, with brain segment-specific expression. AB - Telencephalin (TLN) is a 130 kd glycoprotein expressed exclusively in neurons of the telencephalon, the most rostral brain segment. In the neurons, TLN is localized to soma-dendritic membrane but not to axonal membrane. In this study, we have cloned cDNA encoding rabbit and mouse TLN. The cDNA-derived primary structure of TLN predicts an integral membrane protein with nine tandem immunoglobulin-like domains in an extra-cellular region, a transmembrane domain, and a short cytoplasmic tail. The distal eight immunoglobulin-like domains of TLN show highest homology with the immunoglobulin-like domains of intracellular adhesion molecules (ICAMs) 1, 2, and 3/R. The structural similarity of TLN with ICAMs provides a new and strong link between immunoglobulin superfamily molecules in the nervous and immune systems. TLN is an example of a dendrite-associated cell adhesion molecule involved in the brain's segmental organization, cell-cell interactions during dendritic development, and maintenance of functional neuronal networks. PMID- 7794414 TI - Quantitative determination of intracellular depolymerase activity in Pseudomonas oleovorans inclusions containing poly-3-hydroxyalkanoates with long alkyl substituents. AB - Research regarding the accurate, quantitative degradation of novel poly-3 hydroxyalkanoates has been restricted by the absence of an appropriate monitoring technique. The calibration of a gas chromatograph to poly-3-hydroxyoctanoate reveals a linear relationship between the area under gas chromatograph tracings and polymer weight. With this new method, poly-3-hydroxy-octanoate granules isolated from Pseudomonas oleovorans, which were incubated at 30 degrees C in an alkaline buffer, exhibited a linear degradation rate. Degradation was inhibited by the presence of Triton X-100 and phenylmethylsulfonyl fluoride. The depolymerase was demonstrated to be associated with the polymer granule complex and most likely possessed serine residues at its active site. PMID- 7794416 TI - Allosteric modulation of peripheral sigma binding sites by a new selective ligand: SR 31747. AB - The interactions of a new compound SR 31747 with sigma sites were examined in rat spleen membranes and in human peripheral blood leukocytes (PBL). Nanomolar concentrations of SR 31747 selectively inhibited in a non-competitive manner the binding of the prototypic sigma ligands [3H](+)-pentazocine, [3H](+)-3PPP and [3H]DTG on rat spleen membranes. Characterization of SR 31747 binding sites using [3H]SR 31747 as a ligand showed that this compound binds reversibly, with high affinity to one class of sites on rat spleen membranes (Kd 0.66 nM, Bmax 5646 fmol/mg protein). The pharmacological profile of [3H]SR 31747 binding sites was consistent with the presence of specific sites distinct from classical sigma 1 and sigma 2 receptor subtypes strongly suggesting an allosteric modulation of sigma sites by SR 31747. Similarly, [3H]SR 31747 binding sites were demonstrated on human PBL and also on purified subpopulations of human mononuclear cells (granulocytes, NK cells, T4, T8 and B lymphocytes). Administered to mice by i.p. or oral route 30 min before sacrifice, SR 31747 strongly inhibited the binding of [3H](+)-3PPP to mice spleen membranes with ED50 values of 0.18 and 1.43 mg/kg, respectively. Taken together these results could suggest a potential immunological activity of SR 31747 either directly or through allosteric modulation of peripheral sigma sites. PMID- 7794415 TI - Adenosine attenuates phorbol ester-induced negative inotropic and vasoconstrictive effects in rat hearts. AB - Phorbol esters reduce cardiac contractility and produce coronary vasoconstriction presumably by stimulating protein kinase C (PKC). We tested whether adenosine altered the response to phorbol 12-myristate 13-acetate (PMA) in isolated rat hearts. Hearts, perfused at constant flow and constant heart rate, were exposed to PMA (10 nM) for 30 min and then allowed 30 min of recovery. PMA reduced left ventricular developed pressure (LVDP) from 81 +/- 2 to 49 +/- 3 and 40 +/- 2 mmHg (51 +/- 3% of baseline LVDP) after 30 min infusion and 30 min recovery, respectively. PMA also increased coronary perfusion pressure to 224 +/- 13% of baseline after 60 min. The PKC inhibitor bisindolylmaleimide (0.5 microM) blocked the PMA-induced negative inotropy and vasoconstriction. Adenosine (100 microM) and the A1-agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.1 microM) significantly attenuated the negative inotropic effect of PMA as LVDP was maintained at 81 +/- 4% and 99 +/- 7% of baseline, whereas CGS-21680, an A2 agonist, had no beneficial effect on function (54 +/- 4% of baseline). Adenosine and CGS-21680 (0.1 microM), but not CCPA, significantly attenuated PMA-induced coronary vasoconstriction. These results suggest that adenosine receptor activation may modulate myocardial PKC activity or attenuate the effects of increased PKC activity. PMID- 7794417 TI - Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. II. Structural elucidation. AB - A novel plant growth regulator, pironetin was isolated from the culture broth of Streptomyces sp. NK10958. The structure of pironetin was determined to be (5R,6R) 5-ethyl- 5,6-dihydro-6-[(E)-(2R,3S,4R,5S)-2-hydroxy-4-methoxy-3,5-dimethyl-7- nonenyl]-2H-pyran-2-one by FAB-MS, 1H and 13C NMR, COSY, COLOC, DEPT, IR, X-ray crystallographic analyses and adapted Mosher's method. PMID- 7794418 TI - A new photoaffinity analog of cGMP: potent inhibitor of cyclic nucleotide phosphodiesterase. AB - A purine nucleotide analog, 2'-O-(4-benzoylbenzoyl)guanosine cyclic 3',5' monophosphate (BBcGMP), was synthesized from 4-benzoylbenzoic acid and cGMP. BBcGMP was found to inhibit several types of cyclic nucleotide phosphodiesterases (PDEs) at low concentrations. Besides its activity as a PDE inhibitor, the benzophenone moiety of BBcGMP provides it with UV light-induced photoreactivity toward organic compounds. This photoreactivity of BBcGMP was exploited to radiolabel specifically the light-stimulated cGMP PDE of the rod outer segment with [alpha-32P]BBcGMP. These results suggest that benzoylbenzoic derivatives of cyclic nucleotides can be of general use in the inhibition of cyclic nucleotide PDEs. The results further suggest that radiolabeled cyclic nucleotide derivatives may be useful in the identification and active site determination of cyclic nucleotide-binding proteins and enzymes. PMID- 7794420 TI - Effects on feline pial arterioles in situ of bosentan, a non-peptide endothelin receptor antagonist. AB - The cerebrovascular actions of bosentan, a novel endothelin antagonist with effects at endothelin ETA and ETB receptors, have been examined in individual pial arterioles on the cortical surface of chloralose-anaesthetised cats. Subarachnoid perivascular microapplication of bosentan (0.3-300 microM) had minimal effect on pial arteriolar calibre. Subarachnoid perivascular microapplication of endothelin (10 nM) effected a marked reduction in pial arteriolar calibre (reduced by 39.2 +/- 2.7% from baseline). This vasomotor effect of topical endothelin could be attenuated either by co-administration of bosentan (IC50 approximately 1 microM) or by the intravenous administration of bosentan (17 mumol/kg). These investigations suggest that bosentan (applied topically or systemically) may be a valuable tool in the elucidation of the functional significance of endothelins in the cerebral circulation in vivo. PMID- 7794419 TI - Azidotetrafluorophenyl retinal analogue: synthesis and bacteriorhodopsin pigment formation. AB - The retinal derivative, all-trans-9-(4-azido-2,3,5,6-tetrafluorophenyl)-3,7- dimethyl-2,4,6,8-nonatetraenal, was synthesized by two routes as a potential photoactivatable cross-linking agent for studies in bacteriorhodopsin (BR) of the chromophore interaction with its apoprotein. The retinal analogue formed a stable, moderately functional BR pigment confirming that the ring cavity of the retinal binding site has a significant tolerance for derivatization on that portion of the molecule. Attempts to cross-link the azido chromophore to the protein by photoactivation were unsuccessful. The electron delocalization effect of the conjugated polyene side chain of the retinal appears to interfere with the formation or reactivity of the nitrene intermediate to the extent that photoactivated cross-linking is not achieved. These results demonstrate a limitation to the use of fluorinated aryl azides as photoaffinity reagents. PMID- 7794422 TI - Ankle arthroscopy in industrial injuries of the ankle. AB - Industry-related injuries to the foot and ankle are not uncommon. These cases are often difficult to evaluate with respect to degree of damage and even more difficult to quantitate with regard to functional impairment. This article represents an attempt to determine the role of ankle arthroscopy in the evaluation of ankle injuries that involve compensation or liability. A retrospective review was conducted. The study group consisted of 40 patients who underwent a total of 42 arthroscopic procedures. The patients were evaluated with regard to the mechanism of injury and clinical manifestations. Pain and swelling were the most common preoperative symptoms. The majority of patients had pain localized to the lateral and anterolateral ankle. There were a high percentage of positive bone scans that correlated well with bone pathology but poorly with soft tissue pathology. Computed tomography (CT) scans were equivalent to tomograms in the demonstration of bone pathology. Follow-up was obtained in 24 patients. At least 50% of the patients had some improvement in their symptoms. Thirty-three percent believed there was no change, and 17% said they were worse. Over 70% of the patients were able to return to work, although 20% had to change their occupation. Fifteen percent were considered disabled. In patients without a specific diagnosis, ankle arthroscopy was helpful in establishing a diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794421 TI - Expression and selective inhibition of constitutive and inducible forms of cyclooxygenase. PMID- 7794423 TI - Trends in decreased hospitalization for anterior cruciate ligament surgery: double-incision versus single-incision reconstruction. AB - Over a 4-year period, hospital charges of 151 consecutive anterior cruciate ligament (ACL) reconstructions were retrospectively evaluated. Eighty-one patients who underwent a two-incision ACL central third autogenous patellar bone tendon bone reconstruction were compared with 72 patients who had a single incision endoscopic reconstruction with a similar graft. Charges were adjusted for inflation. There was a statistically significant difference in hospital days (2.8 v 1.57, P = .0001), total hospital charges ($15,063 v $13,520, P = .0001), as well as operating room/hospital ward charges (P = .0001), pharmacy charges (P = .035), and physical therapy charges (P = .001). No statistical difference was observed for anesthesia or laboratory charges. A matched comparison of patients from each group who were in the hospital for 2 days showed a statistically significant reduction in operating room/hospital ward charges (P = .037), but no significant reduction in total costs. There was a trend in both groups toward shorter hospital stays in each successive year. The reduction in charges observed for the endoscopic procedure correlated with a reduction in postoperative hospital days. PMID- 7794424 TI - The posteromedial portal in knee arthroscopy: an analysis of diagnostic and surgical utility. AB - We reviewed 400 consecutive knee arthroscopy cases in a predominantly sports medicine practice to determine (1) the frequency of posteromedial portal usage under a prospectively established set of indications, and (2) the impact of posteromedial portal access on patient diagnosis and management. Diagnostic posteromedial portals were used in 22% of anterior cruciate ligament (ACL) deficient knees, and in 11% of stable knees with nonpatellar (usually meniscal) lesions. When used, posteromedial portal visualization showed treatable lesions 64% of the time, the majority of which were repairable peripheral meniscus tears. In 63% of these cases, no definite lesion had been identified by initial routine anterior portal viewing and probing. Of the 22 patients with posteromedial meniscus tears that were discovered only via posteromedial portal access, 9 had recently undergone anterior portal arthroscopy by other surgeons, during which none of these tears were detected. Posteromedial surgical portals (19 cases) were most useful for synovectomy, posterior cruciate stump resection before arthroscopic reconstruction, and posterior horn medial meniscectomy in exceptionally tight knees. Posteromedial portal access is often useful diagnostically in cases where (1) posteromedial meniscal lesions are frequent (i.e., ACL-deficient knees) and/or suspected on the basis of preoperative symptoms or imaging studies, and (2) full, direct visualization of the entire superior meniscosynovial junction is not possible via standard anterior portals. The option of a surgical posteromedial portal should be entertained whenever frontal approaches for posteromedial instrument work prove inefficient or unsuccessful. PMID- 7794425 TI - Failure strengths of different meniscal suturing techniques. AB - The aim of this study was to measure the failure strengths of three arthroscopic meniscal suturing methods. The techniques investigated were a single horizontal loop, a double vertical loop, and a single vertical loop. Eleven human, lateral menisci obtained at autopsy were cut with a scalpel to simulate peripheral longitudinal tears. The menisci were then repaired with one suture at a time, using each of the three methods in turn. The two parts of the meniscus were then pulled apart using a computer-controlled materials testing machine until failure occurred, either by the suture itself failing or by the suture pulling out because of tearing of the meniscus. The horizontal sutures had a mean failure strength of 29.3 N, whereas the double vertical loop failed at 63.2 N and the single vertical loop at 67.3 N. The horizontal loop sutures and the double vertical loop sutures all failed by pulling out of the meniscus. The single vertical loop sutures failed by rupture of the suture itself. This study showed the superior mechanical characteristics of the single vertical loop suturing system over the other techniques tested. Owing to the more consistent failure strength, decreased costs, and shorter surgical time over the double vertical loop system, the single vertical loop technique is recommended for arthroscopic meniscal repair. PMID- 7794427 TI - The arthroscopic Mumford procedure: an analysis of results. AB - A total of 50 arthroscopic distal clavicle resections were performed for acromioclavicular joint pathology at our institution between 1990 and 1993. Follow-up on 50 shoulders (100%) was obtained at an average postoperative time of 2 years. Data were collected via physical examination, radiograph review, University of California at Los Angeles (UCLA) shoulder score, and questionnaire. Average patient age was 42 years. Preoperatively all patients showed acromioclavicular joint tenderness, whereas 80% had a positive adduction test. The diagnosis of acromioclavicular degeneration was made by a combination of physical examination and radiographs (100%), acromioclavicular joint injection (4%), bone scan (44%), and magnetic resonance imaging (30%). Intraoperatively, a Claviculizer (Smith-Nephew Dyonics, Andover, MA) burr was used through standard portals in a subacromial approach to the acromioclavicular joint. There were no intraoperative complications. Forty-one patients (82%) had their general anesthetic augmented with an intrascalene block, and all procedures were done on an outpatient basis. The average distal clavicle resection was 14.8 mm. Calcifications within the resected clavicle zone were noted in the shoulders of four of the patients (16%) who returned for radiographic follow-up. The UCLA shoulder score ranked 47 shoulders (94%) good to excellent and 3 fair (6%). Subjective patient satisfaction recorded 47 (94%) good to excellent results, with an average pain relief grade of 87%. Forty-five patients (98%) would recommend the procedure. The arthroscopic Mumford procedure effectively treats acromioclavicular joint pathology. The amount of bone removed can be precisely determined with the Claviculizer burr and reliably reproduced. The procedure has low associated morbidity and high patient satisfaction regarding functional outcome. PMID- 7794426 TI - A comparison of outpatient and inpatient anterior cruciate ligament reconstruction surgery. AB - The feasibility of outpatient anterior cruciate ligament (ACL) surgery has not been reported in the literature. We evaluated outpatient ACL surgery by comparing outpatient versus inpatient pain control, narcotic consumption, postoperative complications, recovery time, and cost analysis. Thirty-seven ACL reconstructions were performed in 37 patients over a 16-month period. Twenty-five of the patients had surgery performed as outpatients and 12 as inpatients. One of the outpatients required hospitalization because of excessive nausea and vomiting and another for urinary retention. Only 2 of the 25 outpatients (8%) believed that they should have been hospitalized for pain control. Based on a visual analog scale, pain severity, pain frequency, and pain relief were measured, and no statistically significant difference (P < .05) was noted between the groups, although the data suggested that the inpatients were slightly more comfortable. There were no differences in rehabilitation or in regaining full range of motion of the operated knee. Also, the only postoperative complication in both groups occurred in an inpatient who developed arthrofibrosis. Cost analysis showed that outpatient ACL reconstruction was cost effective. The average inpatient cost was $9,220 (2.4 hospital days) compared with the average outpatient cost of $3,905. This reflected a savings of 58%. These results show that outpatient ACL reconstruction surgery is possible in the appropriate patient without harm to the patient and with a significant cost savings. PMID- 7794428 TI - The use of topographical landmarks to improve the outcome of Agee endoscopic carpal tunnel release. AB - A modified approach to endoscopic carpal tunnel release has been developed and tested in 60 cadaveric specimens by three surgeons using the Agee endoscopic carpal tunnel release system. The modified approach, which includes specific localization of the hook of the hamate, flexor retinaculum, and the superficial palmar arch utilizing topographical landmarks, avoids entry into Guyon's canal and injury to the ulnar artery and nerve, median nerve, and common digital nerves. Use of the anatomic approach resulted in significantly superior results. There were fewer incomplete releases, and fewer surgical passes were required, for the inexperienced surgeons. When these anatomic considerations were not included, the learning curve was much steeper. For surgeons planning endoscopic surgical release of the transverse carpal ligament, the described topographical approach improves the technical competence with the procedure and reduces the number of complications and learning curve associated with new procedures. We recommend the use of topographical landmarks and other anatomic considerations during endoscopic carpal tunnel release. PMID- 7794429 TI - Arthroscopic stabilization for recurrent anterior shoulder dislocation: results of 59 cases. AB - Fifty-nine patients with recurrent anterior dislocation of the shoulder underwent the Morgan arthroscopic stabilization with transglenoidal suture of the inferior glenohumeral ligament. All patients were followed-up for an average of 49 months (range, 29 to 71 months). Using Rowe's scoring system, the overall objective results were disappointing. There were 33% excellent results, 9% good, 9% fair, and 49% poor. Twenty-six patients had a further dislocation, and 3 others had recurrent subluxation on average 13 months after the operation. The failures were associated with a preoperative clinical finding of inferior hyperlaxity as demonstrated by a positive sulcus sign, a preoperative radiological finding of a bony lesion on the anterior edge of the glenoid, or an arthroscopic finding of extended ligamentous lesions at the time of operation. The results of this study are clearly worse than those reported by other investigators. Direct comparison between the reported studies is problematic and is discussed. It was concluded that arthroscopic stabilization should only be performed by interested specialists as part of controlled clinical trials. PMID- 7794430 TI - Neural anatomy of the glenohumeral ligaments, labrum, and subacromial bursa. AB - The neural histology of the human shoulder ligaments, glenoid labrum, and subacromial bursae were studied using a modified gold chloride stain. Two morphological types of mechanoreceptors and free nerve endings were found in the ligaments. Slow adapting Ruffini end organs and rapidly adapting Pacinian corpuscles were identified in the superior, middle, inferior, and the posterior glenohumeral ligaments. These specialized proprioceptive nerve endings were also found in the coracoclavicular, and coracoacromial ligaments. Only free nerve endings were found in the glenoid labrum and these were located in the peripheral half. Scattered free nerve endings were found throughout the subacromial bursae. This is the first histological evidence of neural receptors in the human shoulder ligaments, glenoid labrum, and the subacromial bursae. Any disruption of the labrum or these ligaments by trauma or surgery can deprive the shoulder of mechanical stability, and may cause a decrease in proprioception because of the loss of these afferent neural receptors. Removal of symptomatic, inflamed bursae may decrease pain signals from this area of the shoulder. PMID- 7794431 TI - Treatment of articular defects with meniscal allografts in a rabbit knee model. AB - Deep-frozen allogeneic meniscal grafts for the treatment of articular cartilage defects were performed experimentally. Osteochondral defects 3 mm in diameter were created bilaterally on the medial femoral condyles of 50 Japanese white rabbits. A meniscus was then grafted into the defect in the left knee, and the right knee was left untreated. At various periods from 2 to 24 weeks postoperatively, the rabbits were killed and macroscopic and histologic examinations were performed. Two weeks after operation, the grafted meniscus was bonded to the floor of the defect. After 12 weeks, chondrocytes producing matrix granules was shown by electron microscopy. After 24 weeks, a congruous articular surface was formed. With time, cellular elements infiltrated into the graft from the surrounding tissues, and gradually increased in penetration. Weight bearing in the early stage after operation did not degrade the grafted menisci, and no changes were shown in the opposing cartilage of the tibia. Deep-frozen allogeneic menisci may be useful as a biological implant to repair articular cartilage defects in this model. PMID- 7794433 TI - Optimizing arthroscopic knots. AB - Arthroscopic repairs, such as those for shoulder instability, are commonly performed. However, the failure rate after arthroscopic repair appears to be higher than with open surgery. These failures may relate to the challenge of tying secure knots arthroscopically. Many knots tied arthroscopically commonly consist of an initial slip knot to remove slack, and a series of half-hitches. Half-hitches, instead of square throws, are difficult to avoid and result when asymmetrical tension is applied to the strands. For this reason, the security of knots tied arthroscopically may not be equivalent to square knots and a greater rate of failure may occur. The purpose of this study was to determine (1) the security of various arthroscopic knots under cyclic and peak loading conditions, (2) how the surgeon can modify the method or sequence of half-hitch throws to minimize knot slippage or breakage, and (3) whether using an arthroscopic knot pusher affects the security of the same knot tied by hand. The most secure knot configurations were achieved by reversing the half-hitch throws and alternating the posts. These knots performed significantly better than all other knots tested (P < .002). Thus the surgeon can control the holding capacity and minimize suture loop displacement by proper alternation of the tying strands and reversal of the loop when placing the hitches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794432 TI - Arthroscopic fixation of superior labral lesions using a biodegradable implant: a preliminary report. AB - Twenty-two patients were treated for symptomatic lesions of the superior glenoid labrum in association with instability of the tendinous insertion of the long head of the biceps brachii. A biodegradable implant was used to fix the labrum to the bony glenoid using an arthroscopic technique. At 2-year average follow-up, satisfactory results were obtained in 86% of the patients. Two patients, both of whom had undergone concomitant subacromial decompression, continued to complain of pain after the procedure; 3 patients had restricted motion postoperatively, and 1 required manipulation under anesthesia. Twelve of 13 overhead athletes were able to return to full premorbid function. Arthroscopic fixation of unstable lesions of the superior labrum led to a resolution of symptoms in the majority of patients. There were no complications related to the use of the biodegradable implant. PMID- 7794434 TI - Comparison of two regional anesthetic techniques for knee arthroscopy. AB - This study compares the efficacy of "3-in-1 block" versus femoral nerve block for knee arthroscopy. One-hundred patients had a 3-in-1 block; 180 patients had a femoral nerve block. The 3-in-1 block provided anesthesia in 75 patients; 20 patients needed supplementary local anesthesia. Five patients required a general anesthesia to complete the operation. The femoral nerve block was effective in 88 patients; 90 patients needed intravenous flunitrazepam and/or fentanyl; 2 patients needed general anesthesia. The 3-in-1 block provided more satisfactory muscle relaxation and a longer postoperative analgesia than femoral nerve block. No side effects were recorded in either group. Our results suggest that the 3-in 1 block is the most effective technique of regional anesthesia for knee arthroscopy. PMID- 7794435 TI - Tenosynovial giant-cell tumor in the knee joint. AB - We report the case of a tenosynovial giant-cell tumor causing limitation of extension of the knee. The tumor was treated successfully by arthroscopic removal. PMID- 7794436 TI - Arthroscopic resection of a chondroblastoma in the knee. AB - A 13-year-old boy with the diagnosis of osteochondritis dissecans underwent arthroscopic examination of his knee joint. At surgery a cartilaginous mass in the medial femoral condyle was identified. Biopsy samples confirmed the diagnosis of chondroblastoma, which was removed completely through the arthroscope. A second arthroscopic examination of the knee was conducted at 6 months, and showed no residual disease. Clinical and radiographic follow-up of the affected joint 5 years after surgery was satisfactory. Arthroscopic removal of an intra-articular tumor is an attractive treatment alternative, provided the lesion is accessible and there is no suggestion of a malignancy. PMID- 7794438 TI - A unique complication following arthroscopic anterior cruciate ligament reconstruction. AB - The use of the middle third of a patellar tendon with bone blocks is a common and well-accepted technique for arthroscopic reconstruction of the anterior cruciate ligament. We report here a disconcerting fracture/avulsion pattern of the patella/patellar tendon mechanism that occurred in the early postoperative period. PMID- 7794437 TI - Osteonecrosis after arthroscopic medial meniscectomy. AB - Osteonecrosis of the medial femoral condyle is an uncommon complication of meniscal surgery. Whether this disease is associated with the original medial meniscus lesion or with the arthroscopic procedure is not yet known. We present two cases in which osteonecrosis has developed shortly after arthroscopy was performed for medial meniscus pathology. Magnetic resonance imaging has been the best tool to diagnose and follow up the changes in the involved area. Concerning the etiology, the authors raise the question of whether the medial compartment overloading observed in both of these cases had any significant meaning. Osteonecrosis following meniscal surgery in relatively young patients seems to have a good prognosis when correctly treated, with avoidance of weight bearing. PMID- 7794439 TI - Pseudoaneurysm complicating knee arthroscopy. AB - Pseudoaneurysm formation is a rare complication of knee arthroscopy. Cases reported in the literature have involved the popliteal, superior and inferior medial geniculate, and the inferior lateral geniculate arteries. These cases have all been described as presenting within 2 to 3 weeks of the arthroscopic procedure. Described here are two unique cases, the first a delayed presentation and the second involving the recurrent anterior tibial artery. PMID- 7794440 TI - Arthroscopic roofplasty: correction of an extension deficit following conservative treatment of a type III tibial avulsion fracture. AB - Extension loss following nonoperative treatment of a Type III tibial avulsion fracture does occur. Arthroscopic roofplasty (notchplasty) and scar excision are described to regain complete extension without compromising knee stability. PMID- 7794441 TI - Arthroscopic repair of a posterior cruciate ligament avulsion. AB - Isolated posterior cruciate ligament injuries are rare and their management is controversial. Bony avulsion fractures have commonly been repaired with open reduction and internal fixation using the posterior approach described by Trickey. However, this approach does not lend itself to detection and repair of associated injuries. We report the case of a posterior cruciate ligament avulsion that was arthroscopically reduced and stabilized with cannulated screws. This technique provided rigid fixation for early rehabilitation and allowed concomitant arthroscopic examination of the knee for any associated injuries. PMID- 7794442 TI - Arthroscopically assisted placement of a supracondylar intramedullary nail: operative technique. AB - The use of retrograde interlocking intramedullary nails has been described for the treatment of selected supracondylar fractures. A medial parapatellar incision and arthrotomy with its attendant morbidity is generally used for nail placement. Although a closed technique of nail placement has been described, the risks of damaging intra-articular structures with a blind approach have precluded the widespread use of this method. In this article, we present a simple, arthroscopically assisted method for the retrograde intramedullary nailing of supracondylar femoral fractures. This technique affords the potential benefits of intramedullary fixation of these fractures while avoiding the morbidity and complications associated with an arthrotomy. Potential benefits over the standard placement using an arthrotomy include earlier ambulation and soft tissue healing, decreased risk of damage to the knee joint, earlier convalescence with decreased hospitalization time, and better cosmesis. PMID- 7794443 TI - T-Fix endoscopic meniscal repair: technique and approach to different types of tears. AB - Endoscopic meniscus repair using the T-Fix suture device (Acufex Microsurgical, Inc, Mansfield, MA) allows ease of suture placement for meniscus stability without the problems associated with ancillary incisions such as neurovascular compromise. It is ideal for the central posterior horn tears that are difficult using conventional techniques. Vertical tears, bucket handle tears, flap tears, and horizontal tears can be approached using a temporary "anchor stitch" to stabilize the meniscus before T-Fix repair. The basic method of repair and our approach to these different types of tears is presented. PMID- 7794444 TI - An alternative cruciate reconstruction graft: the central quadriceps tendon. AB - The central quadriceps tendon, above the patella, is thicker and wider than the patella tendon. Using precise technique, one can obtain a tendon graft for cruciate reconstruction with 50% greater mass than a patellar tendon bone-tendon bone graft of similar width. The central quadriceps tendon graft may be harvested by a second surgeon while the first surgeon is simultaneously accomplishing notch plasty and tunnel placement for cruciate ligament reconstruction. Consequently, this cruciate ligament reconstruction graft offers time savings as well as greater tendon volume. The central quadriceps tendon graft is difficult to harvest, with significant risk of entering the suprapatellar pouch and losing knee distension during ACL reconstruction. By careful adherence to the technique described in this article, the surgeon can obtain this reconstruction graft safely. It is important to recognize the anatomic subtleties of the proximal patella, which include a curved proximal surface, dense cortical bone, and closely adherent suprapatellar pouch. Proper technique is of utmost importance in obtaining this tendon graft safely and efficiently. PMID- 7794445 TI - Ethics and health. Interview by Eilif Liisberg. PMID- 7794446 TI - Ethics of nursing and midwifery: responding to change. AB - Nurses and midwives are taking an increasing interest in ethical matters in their professions. Although the conditions in which they work vary immensely and are undergoing rapid change, it is possible to detect certain basic notions of patient care which transcend cultural, socioeconomic and technological differences. PMID- 7794447 TI - Reaching street youth on substance abuse. AB - Street children and youth involved in substance abuse are often felt to be the hardest people in the world to reach with counselling, as well as those most obviously in need of it. The idea of making a work of art that both captures their imagination and steers them towards a safer way of life may seem more like wishful thinking than a practical proposal, but the author explains how it is done. PMID- 7794448 TI - The Moscow street children project. AB - More and more young people are living on the streets of Moscow and getting involved in substance abuse and crime. The authors outline the effort being made by the International Health and Temperance Association to organize a response to this rapidly growing problem. PMID- 7794449 TI - Technology for the continuous improvement of the quality of health care. AB - Since medical technology impinges on the structure, process and outcome of health care it has a profound effect on attempts to achieve improvement in this field. The present article discusses the links between medical technology and continuous quality development, with particular reference to utilization, appropriateness and cost-benefit. PMID- 7794450 TI - Towards evaluation of the quality of care in health centres. AB - There is wide acknowledgement that quality assurance is desirable in primary health care. Considerable success has been achieved in this field by the Iberian Programme of Training and Implementation of Quality Assurance Activities in Primary Health Care, the basis for which is outlined below. PMID- 7794452 TI - Promoting the health of women of non-English-speaking backgrounds in Australia. AB - Immigrants with non-English-speaking backgrounds face many linguistic and cultural barriers when trying to use Australia's health services. Gender inequities make matters especially difficult for women with such backgrounds, who largely belong to the lower socioeconomic categories. The present article describes two health promotion projects whose success is largely attributable to their recognition of the difficulties faced by these women and to the strategies devised to overcome them with the aid of liaison workers and bilingual community educators. PMID- 7794451 TI - Trained traditional birth attendants as educators of refugee mothers. AB - Following training courses for traditional birth attendants among refugee Afghan women in Pakistan, a survey was conducted to test the knowledge and practices of the participants and of mothers whose babies had been delivered by them, using untrained birth attendants as the basis for comparison. Marked improvements in knowledge and skills were demonstrated, and recommendations made by the trained birth attendants about breast-feeding, maternal nutrition, immunization and hygiene were generally followed by mothers before and after delivery. Furthermore, far fewer complications and deaths were associated with deliveries performed by trained birth attendants than with those conducted by their untrained colleagues. The training of traditional birth attendants was clearly an effective way to educate women about hygiene and health. PMID- 7794453 TI - Interns as health educators. AB - Interns are being used in two experimental health education projects in a rural area of India. In one the interns talk to mothers waiting with their children at an immunization clinic; in the other they train volunteer schoolchildren to act as school health guides in a child-to-child programme. PMID- 7794454 TI - Confronting the health hazards of industrialization in Malaysia. AB - The authors outline the steps being taken in Malaysia aimed at persuading people to avoid the unhealthy lifestyles commonly associated with socioeconomic development and increased affluence, and to adopt health dietary and other habits. PMID- 7794455 TI - Health education in farming communities. AB - The author outlines the ways in which health messages have been given to agrarian communities in Tigray, Ethiopia. Special attention has been given to assessing the people's knowledge base initially, to communicating with them at the most appropriate times and places and in the local language, and to the use of role playing. PMID- 7794456 TI - Cost-effective screening of schoolchildren for refractive errors. AB - Uncorrected refractive errors are the main cause of severely impaired vision in India. This in itself indicates that there is a shortage of basic eye care services and spectacles, and too little public awareness of the need for them. A simple method for screening schoolchildren for refractive errors is described and the results are analysed. Evaluation of the materials used and the accuracy of the screening shows that this method can be used successfully by teachers. PMID- 7794457 TI - First WHO Collaborating Centre for Women's Health. PMID- 7794458 TI - Distances travelled to reach surgical eye camps. PMID- 7794459 TI - District health libraries in Tanzania. PMID- 7794460 TI - Sanitary wells versus boreholes for drinking-water. PMID- 7794462 TI - Organ transplants and donorship. PMID- 7794461 TI - Literacy campaign and health education go hand in hand. PMID- 7794463 TI - General practitioners for primary health care in Russia. AB - General practice is being introduced into the Russian health system to bolster primary care. The main features of this undertaking are outlined below. PMID- 7794464 TI - National health policy for traditional medicine in India. AB - External pressures have combined to erode the practice of India's traditional medical systems to such an extent that they are in danger of becoming extinct. A better balanced national health policy could go a long way towards reversing this trend. PMID- 7794465 TI - Viet Nam: profit and loss in health care. AB - The decline of Viet Nam's once highly effective commune health stations has resulted in the over-prescription of drugs and the danger of lower public health standards. It must be recognized that private and public activities form part of the same health system, and need firm supervision if it is to flourish. PMID- 7794466 TI - Choice of traditional or modern treatment in west Burkina Faso. AB - A recent survey shows that patients turn to modern medicine more than traditional medicine for most of their needs except rheumatic and neurological complaints. However, the preferences stated are influenced on the one hand by the much lower cost of traditional services, and on the other by official disapproval of animistic practices. PMID- 7794467 TI - The strengths and weaknesses of Turkish bone-setters. AB - Twelve bone-setters and 20 clients of bone-setters were interviewed to gather information about the nature and popularity of these traditional health services. The results suggest a high degree of confidence in the bone-setter's art, though this is not always well founded. PMID- 7794468 TI - The natural toothbrush. PMID- 7794469 TI - News about AIDS. PMID- 7794470 TI - Need for action against tuberculosis. PMID- 7794471 TI - Anticholinergic effects in a depressed parkinsonian patient. AB - Depression is commonly associated with idiopathic Parkinson's disease. Various antidepressants can be helpful in the treatment of this type of depression. Anticholinergic medications are at times used for treating the motor symptoms of parkinsonism. While some authors have reported euphorigenic effects from anticholinergics in other groups of patients, generally, they have not been used in the treatment of depression, with or without parkinsonism. In the case presented, a depressed patient with Parkinson's disease on levodopa/carbidopa and fluoxetine was given benztropine for his motor symptoms. The result was some improvement in his motor symptoms and a wide, dose-related spectrum of other central nervous system changes ranging from delirium to mania, hypomania, and euthymia from a "baseline" of residual depression. At a very low dose (0.25 mg per day), benztropine appeared to have an augmenting antidepressant effect that rendered the patient euthymic. PMID- 7794472 TI - Sundown syndrome in severely demented patients with probable Alzheimer's disease. AB - A retrospective review of 71 patients with probable Alzheimer's disease was analyzed with respect to nursing evaluations of sundowning status (recurring confusion or agitation in the late afternoon or early evening). The prevalence of sundowning (including probable sundowners) was 24%. Sundowners and non-sundowners differed with regard to number of sedatives received daily, particularly chloral hydrate, and the number of days on the inpatient unit. There were no differences between sundowners and non-sundowners with respect to other types of medications, medical diagnoses, current age, age of onset of Alzheimer's disease, or Mini Mental State Exam. Restlessness was the most common sundowning behavior, although multiple behavioral disturbances were seen. This survey suggests that the sundown syndrome is a common problem in severely demented Alzheimer's patients and requires further study. PMID- 7794473 TI - Disruptive nocturnal behavior in Parkinson's disease and Alzheimer's disease. AB - Disruptive nocturnal behavior, often referred to as sundowning, is a commonly encountered clinical problem in most forms of dementia. This study compared disruptive nocturnal behavior in patients with Alzheimer's disease (AD) and Parkinson's disease (PD). Questionnaire data were collected from 60 AD and 48 PD caregivers. Respondents were asked to record the typical time of day when any of seven disruptive behaviors were evidenced in their patients, if at all. Two scores were computed: (1) a sundowning score (number of nocturnal disruptive behaviors, range 0-7), and (2) a total score (number of disruptive behaviors without regard to time, range 0-7). Results indicated PD patients were more likely than AD patients to exhibit disruptive nocturnal behavior. The dose, timing, or number of years on antiparkinsonian medication were not related to nocturnal disruptive behavior within the PD patient group. These findings raise the possibility that sundowning in PD patients may be a manifestation of dopaminergic depletion within the basal ganglia or other abnormalities involving the cholinergic, serotoninergic and/or noradrenergic systems in the brainstem. PMID- 7794474 TI - Primitive reflexes in Alzheimer's disease and vascular dementia. AB - Data on the prevalence and clinical value of primitive reflexes (PRs) in dementia are controversial, mainly due to a lack of standardization of the methods by which these signs are elicited and scored. A standardized protocol was used to investigate eight PRs in 20 patients with Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 20 control subjects for each group. Both patient groups showed considerably more PRs than the control groups. The prevalence of PRs was related to the severity of dementia. No single reflex or combination of PR pathognomonic for dementia could be distinguished. The PR profile of AD and VD patients were similar. PMID- 7794476 TI - Delusions of infestation during delirium in a patient with restless legs syndrome. AB - A case is described in which delusions of infestation developed during delirium secondary to pneumonia in a patient with restless legs syndrome (RLS). This case demonstrates how tactile sensations may precede and give rise to delusional misinterpretations. Since RLS is relatively common in elderly people and may be due to a treatable cause such as iron deficiency, it is worth considering this syndrome in patients with delusions of infestation. PMID- 7794475 TI - Disabling parkinsonism due to lithium: a case report. AB - Two cases of disabling parkinsonism have been previously reported in association with lithium treatment and only one occurred without other signs of lithium toxicity. We report a case of an elderly female who suddenly developed disabling parkinsonism, apparently as a side effect from treatment with lithium carbonate without other signs of lithium toxicity. All neurologic symptoms completely resolved on discontinuation of lithium. Resuming lithium at serum levels below 0.7 mmol/L resulted in no further neurologic side effects, but serum levels of 0.7 to 0.9 mmol/L resulted in the return of mild Parkinson's symptoms. Older age, longer duration of lithium treatment, and high therapeutic levels of lithium may be risk factors for this side effect. Implications for clinicians are discussed. PMID- 7794477 TI - Clomipramine treatment of paraphilias in elderly demented patients. AB - Sexually inappropriate conduct often accompanies the disinhibition associated with dementia and neuropsychologic deficits. Management of these behaviors is problematic and time consuming. We report two cases in which paraphilias responded to treatment with clomipramine. This effect was not due to the sexual side effects of the drug (e.g., decreased ability to sustain an erection or orgasm). Careful monitoring of the elderly patient is required during treatment with clomipramine, particularly with regard to orthostasis, the increased risk of falls, and worsened confusion secondary to the potential risks of anticholinergic delirium and toxicity. PMID- 7794478 TI - Comparison of new and traditional methods for detection of senile plaques in Alzheimer's disease. AB - The pathologic diagnosis of Alzheimer's disease (AD) rests upon the identification of senile plaques and neurofibrillary tangles (NFT) in brain tissue. Methods for staining these structures vary in their sensitivity. Six different silver stains and immunocytochemistry for the beta-amyloid (A beta) peptide were compared for sensitivity in staining of plaques and tangles. For staining of plaques, the silver stains fell into two groups: one group stained primarily large, distorted neurites in classic plaques, and the other stained primarily fine, filamentous elements in diffuse plaques and at the periphery of classic plaques. Our recently developed "quick silver" method demonstrated the highest number of plaques. Sensitivity of NFT staining also varied considerably. The quick silver and Yamamoto-Hirano methods were best for staining both plaques and NFT. PMID- 7794479 TI - Memory deficits in a demented patient with probable corticobasal degeneration. AB - Anterograde and retrograde amnesia in a patient with probable corticobasal degeneration (pCBD) and dementia were studied in a university medical center setting. The patient with pCBD and four comparison patients of comparable global mental status (Mini-Mental State Exam) who met NINCDS-ADRDA criteria for Alzheimer's disease (AD) were included. Standard neuropsychological tests of naming, intelligence, achievement, verbal fluency, anterograde and remote verbal and visuospatial memory, and motor skill learning were given. The pCBD patient exhibited a progressive asymmetric akinetic-rigid syndrome, which was unresponsive to Sinemet. His initially mild, intellectual deficits consisted of apraxia, slowed speech, and word-finding and memory difficulties. Over a 2-year period, a dementia syndrome developed, which involved more-serious deficits in praxis and naming, as well as impairments in spelling, calculation, verbal fluency, IQ, anterograde verbal and visuospatial memory, and motor skill learning. When tested by recall methods, the pCBD patient exhibited marked deficits on several tests of remote memory; however, on recognition testing, he performed normally on the Famous Faces Test and on a test of geographical knowledge, which measures remote visuospatial memory. By contrast, the four AD patients, who showed equivalent naming difficulties, less-severe fluency deficits, and normal motor skill learning, showed severe impairments in recalling and recognizing the names of famous people from photographs. A magnetic resonance imaging (MRI) scan of the pCBD patient showed marked frontal and parietal lobe atrophy and central atrophy, with ventriculomegaly that was greater on the left side of the brain. The temporal lobes were relatively spared, and the amygdalae, hippocampi, and temporal horns were of normal size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794480 TI - Pharmacotherapy of cognitive impairment in Alzheimer's disease: a review. AB - Experimental pharmacotherapy of cognitive impairment in Alzheimer's disease has seen a recent proliferation of drug trials involving a wide variety of drugs. Many of the earlier studies focused on cholinergic agents. However, subsequent advances in basic and biological sciences have broadened the scope of therapeutic strategies beyond the neurotransmitter approaches to include neurotrophic, metabolic-enhancing, membrane-modifying, and antitoxic agents, and have also provided rationale for developing antiamyloid and anti-infective therapies. For the clinician, it has not been easy to keep abreast of these developments. In this article, I present an overview of the cognition-enhancing drugs that have been used in the past, of those currently under investigation, and of new drugs and strategies that are likely to receive attention in the next few years. PMID- 7794481 TI - Depressive symptoms in Alzheimer's disease and multi-infarct dementia. AB - We examined the prevalence of major depression, depressed mood/anhedonia, and subjective and neurovegetative symptoms of depression that were unaccompanied by depressed mood/anhedonia in patients with clinically-diagnosed Alzheimer's disease (AD) and multi-infarct dementia (MID). The specificity of subjective and neurovegetative depressive symptoms for depressed mood in dementia was examined, as was the impact on depression of clinical variables such as family history, patient age, and dementia severity. Subjects were 105 outpatients who met DSM-III R criteria for AD (n = 67) or MID (n = 38). Depressed mood/anhedonia was frequently noted in both the AD (40.3%) and MID (34.2%) groups. One or more depressive symptoms, not accompanied by depressed mood/anhedonia, were also common in AD and MID (49.3% and 36.8%, respectively). Major depression was relatively uncommon in AD (10.5%) but was noted more frequently in MID (29.0%). Among AD patients, neurovegetative symptoms of depression were not any more common in patients with depressed mood/anhedonia than in those without depressed mood/anhedonia. Subjective symptoms of depression were also not significantly associated with depressed mood/anhedonia. The study highlights the importance of viewing major depression, depressed mood-anhedonia, and other depressive symptoms (subjective and neurovegetative) as separate entities in AD and MID. PMID- 7794482 TI - Implementation of the global strategy for health for all by the year 2000. Second evaluation. Eighth report on the world health situation. PMID- 7794483 TI - The incorporation of partial shielding of the spinal cord in a tissue deficit compensator in radiotherapy of the thorax. AB - A method to determine the shape of a patient by placing radiopaque wires and chains on the skin and taking two isocentric X-ray films is described. The wire locations are reconstructed by X-ray stereo photogrammetry, and a beam's eye view of the wire frame structure can be obtained with reference to the original setup of the "stereo-pair" films. An algorithm for paving between the wires with triangular plates is described which allows the calculation of the tissue deficit distance and compensator thickness. The depth and distance to points on the spinal cord are calculated, and the dose rate is calculated using a standard irregular field computation program. The limit for spinal cord tolerance is specified in terms of the maximum daily dose based on an equivalent dose formula. The additional thickness of compensator, required for the posterior field compensator to satisfy the tolerance limit, is calculated. The technique readily accommodates the kyphotic and scoliotic spine and has been in routine clinical use for seven years. PMID- 7794484 TI - 3D conformal radiotherapy in the sagittal plane for centrally located thoracic tumors. AB - One hundred patients, recently treated at the University of California, San Francisco (UCSF) with radiotherapy for lung and esophageal cancer, were studied. Three subsets of these patients were defined based on tumor location to test how commonly the use of three-dimensional (3D) conformal radiotherapy (3DCRT) could improve significantly the delivery of high dosages. Comparisons were made between isodose distributions and dose volume histograms (DVHs) of patients' prior computed tomography (CT)-based treatment plans and newly generated 3D-based treatment plans. The use of beam angles outside the conventional horizontal plane did not significantly improve the dose distribution for patients if a peripheral mass was the target volume. Patients with a target volume involving the central thorax represented a subset (> 40% of the patients) who would have benefited the most from the use of nonconventional beam angles. In these patients, sagittal coplanar beams (sagittal Y technique) reduced the dose to 30% of the lung volume from 30% to 5%. Doses to the spinal cord and heart were slightly higher than with conventional techniques but were within the tolerance of normal tissues. The sagittal Y technique allows an escalation in total dose to the tumor without increasing dose to normal tissues beyond their tolerance. PMID- 7794485 TI - Surface dose for tangentially incident photon beams in the presence of air gap and air cavity. AB - Dose to a surface parallel to an incident photon beam has been investigated in the presence of air gaps and air cavities. Measurements have been made in an acrylic phantom with a parallel plate chamber. Photon beams of Co 60, 4-MV, 6-MV, and 15-MV X-rays have been investigated. The results of our measurements show that in the case of air gaps, the dose reduction to a tangential surface is considerable. On the other hand, the dose reduction is 2% or less in the case of air cavity for volumes encountered in clinical situations. PMID- 7794486 TI - Dosimetric effects of matching electron fields with cobalt 60 fields in the management of head and neck cancer. AB - The dose distributions in a blocked Co 60 beam with the area under the block irradiated with a 9-MeV electron beam at a nominal source to surface distance (SSD) of 100 cm and at an extended SSD of 115 cm were determined. The photon block was simulating the spinal cord shielding used when treating the posterior neck. A hot spot of 10% appeared close to the junction on the side of the photon field when electron treatment was given at a nominal SSD of 100 cm. At 115 cm SSD, the magnitude of the hot spot on the side of photon field increased to 20% and a cold spot on the order of 10% appeared in the distal area of the irradiated volume treated with electrons. A gap of 0.5 cm between the light field edges of the photon field and the electron field reduced the hot spot from 20% to 10% on the side of photon field. However, the magnitude of the cold spot on the side of electron field increased to 20%, and it appeared across the irradiated volume. Considering the limitation of the design of the electron applicators, which precludes the use of a nominal SSD of 100 cm for head and neck treatments, it is recommended that no gap should be allowed between the photon fields and the extended SSD electron fields. Clinically a limited hot spot of 20% is considered more acceptable than a cold spot of 20% extending from proximal to distal areas of the treatment volume. PMID- 7794487 TI - Design specifications for a treatment stand used for total body photon irradiation with patients in a standing position. AB - One total body photon irradiation technique used to treat patients employs a standing treatment position and a horizontally directed high-energy photon field. This standing technique presents special problems, including keeping the patient immobile during treatment and offering protection from injury if the patient develops weakness or loss of consciousness due to either medication (anxiolytics, narcotics, or antiemetics) or other causes. In this article we describe a treatment stand designed to manage these problems and use effectively total body photon irradiation. This stand has been used successfully in our clinic at the University of Minnesota for several years and has met or exceeded the original design expectations. PMID- 7794488 TI - Evaluation of a well-type ionization chamber for calibration of HDL and LDR brachytherapy sources. AB - The Atomlab 44D well-type ionization chamber is being evaluated for calibration of high dose rate (HDR) Ir-192 and low dose rate (LDR) Cs-137 sources. The chamber has a flat response (sweet spot) of +/- 0.5% along approximately 3.5 cm for an Ir-192 HDR linear source and 3 cm for a Cs-137 LDR spherical source. The short-term stability of the chamber was determined using a cylindrical Cs-137 source positioned in the sweet spot region. The chamber response over a range of 17.4 mCi (644 MBq, Cs-137) and 8.82 Ci (326 GBq, Ir-192) is evaluated. The chamber may be used for calibrating the activities of both HDR Ir-192 and LDR brachytherapy sources. PMID- 7794489 TI - Multisectional planning for external beam radiotherapy: a "poor person's" alternative to three-dimensional treatment planning. AB - Recent technical advances in the field of computers have led to the use of three dimensional dose computation for optimizing a radiation therapy plan. However, in centers which lack such a state-of-the-art technology, one could explore the use of multisectional planning to obtain information about the dose profiles all along the target volume. This article highlights the utility of multisectional planning as an alternative to three-dimensional treatment planning systems for external beam radiation therapy. PMID- 7794490 TI - Constancy of wedge factors in a Siemens Mevatron 74 linear accelerator. AB - The variation of the wedge factor (WF) with field size is an important piece of data which determines the radiation output in treatments using wedge filters. WF is closely related with the accelerator head layout, and the choice of the wedge tray mounted above or below the jaws plays a predominant role. In this work we have studied the WF variations in our linac and found that, in apparent contradiction with the literature, the WF remains constant with field size. Nevertheless, these results cannot be used directly in other linacs, and individual dosimetry must be carried out. PMID- 7794491 TI - Description of a 3D conformal neutron and photon radiotherapy technique for prostate cancer. AB - Several methods have been described to improve the therapeutic ratio of radiotherapy in patients with locally advanced carcinoma of the prostate (LACaP). Studies have shown improved survival and local control in patients treated with neutron irradiation as opposed to photons alone. However, an increased complication rate was observed when conformal field design was not utilized. A 3D conformal mixed neutron/photon technique for LACaP has been developed at this institution. Field shaping for the neutron component is achieved with a multirod collimator. Prior to treatment, all patients undergo a conventional simulation followed by a treatment planning computed tomography (CT) scan. Contours of target and normal structures are entered into the 3D treatment planning system. Beam apertures are designed utilizing beam's eye view display. The photon dose is given in 10 fractions at 1.8 Gy each to the prostate and seminal vesicles (PSVs) and pelvic lymph node (PLN) volumes. The neutron dose is given in 15 fractions at 1.0 Gy per fraction to the PSV volume and 0.6 Gy to the PLN volume. The neutron portion includes a partial transmission block to achieve this dose differential. The treatment planning process, including beam weighting and custom block design, is described. Using these techniques, the neutron dose distributions to the target volumes, bladder, and rectum were comparable to those seen with four-field conformal photon irradiation. PMID- 7794492 TI - Physical characteristics of photon and electron beams from a dual energy linear accelerator. AB - Clinically pertinent data of the photon beams of nominal energy 6 MV and 18 MV from a dual photon energy linear accelerator are measured using a radiation field analyser with semiconductor diodes and ionisation chambers. Percentage depth dose values are compared with available data from other linacs and BJR-17. Measurements made in the buildup region using a parallel plate chamber show a marked increase in the surface dose and dmax shifts by 3 mm and 14 mm for 6 MV and 18 MV photons, respectively as the field size is increased from 4 x 4 cm2 to the maximum. Variations of wedge angles with energy and field size are also determined up to wedge widths of 15 cm for all the four available wedge angles. Isodose plots of both the energies are plotted using semiconductor diodes in a RFA-3 system. Output factors, wedge transmission factors, and shielding tray factors were also measured in clear polystyrene phantom for both the photon energies at the depths of maximum ionisation. Beam characteristics of the electron beams of energies 6, 9, 12, 16, and 20 MeV produced by the Clinac-1800 have also been studied. The characteristics include percentage depth dose, isodose distribution, depth of maximum dose, surface dose, photon contamination, uniformity index, and penumbra. Most of the measurements were carried out using semiconductor detectors, whereas small volume ionization chambers and a plane parallel chamber were kept as standards for comparison. Isodose distributions were drawn from the film densitometry method. Range-energy parameters are obtained from the observed depth dose data. These parameters vary from machine to machine and must be ascertained for individual units. The parameters differ to a considerable extent from their theoretically predicted values but generally follow the trend, experimentally observed by others, for similar types of units. PMID- 7794493 TI - Potential underdosing with the use of electron beam therapy in patients with cervical adenopathy and advanced head and neck cancer. AB - To define the adequacy of electron beam therapy in the treatment of N1-N3 head and neck cancer, 24 patients with primary head and neck cancers and N1-N3 cervical adenopathy received primary radiation therapy with or without chemotherapy for definitive control of their disease. All patients underwent computerized tomography (CT) to assist in the design of treatment to the posterior neck with electron beams after photon therapy to the level of spinal cord tolerance. Treatment with electrons to the posterior neck in patients with N1 disease was adequate in 92% (11/12) of patients. However, in patients with N2 and N3 disease, electron beam treatment failed, because of spinal cord tolerance problems, to cover the disease adequately in 92% (11/12). It is concluded that CT should be employed routinely in patients with N1-N3 neck disease to determine the proper electron energy prescription. For some patients, electron beam may not be appropriate, making it necessary to use individual planning to treat adequately the neck disease and avoid the spinal cord. PMID- 7794494 TI - Modulation of wound healing in Swiss albino mice by different doses of gamma radiation. AB - Changes in wound healing were studied using artificial wounds created either by surgical excision of full thickness skin or partial skin thickness dermabrasion of dorsal skin of Swiss albino mice exposed to 2, 4 and 6 Gy of gamma radiation. There was a significant delay in the wound healing process after exposure to 2 Gy when compared to the controls. With increasing doses of radiation wound healing time was also delayed. However, the differences in wound healing times between all three doses were not significant. The irradiation resulted in a dose dependent delay in the wound contraction and mean wound healing time. The abrasion group was followed until complete epithelialization in the animals exposed to 2, 4 and 6 Gy of gamma radiation. However, no significant difference was observed in the healing time with respect to non-irradiated controls for all the exposure doses used in the present study. PMID- 7794495 TI - A comparison of susceptibility to five antifungal agents of yeast cultures from burn patients. AB - Patients with significant degrees of immunocompromise, such as cancer, AIDS and large burns, who have received significant amounts of antibiotics, may develop infections with yeast organisms. Over a 3-year period, all patients with positive fungal blood cultures and most wounds of patients with large burns considered to be a risk of yeast infection were selected and tested for their susceptibility to five antifungal agents, amphotericin B, ketoconazole, miconazole, diflucan, and 5 fluorocytosine. In all, 244 specimens of yeast were tested: 142 Candida albicans, 52 Candida parapsilosis, 26 Candida tropicalis and 13 Trichosporon beigelii. A limited number of other isolates of Candida (12) were also encountered. All Candida organism were sensitive to amphotericin B. There was wide variation in regard to the susceptibility to the other four agents, with C. albicans and C. tropicalis being largely resistant to miconazole and ketoconazole. T. beigelii was recovered in 13 patients. One-half of these organisms was resistant to amphotericin B. Awareness of variations in species and susceptibility are helpful in the selection of appropriate therapeutic antifungal agents. PMID- 7794496 TI - The effect of thermal injury on gastric emptying in rats. AB - Gastric distension and gastrointestinal discomfort are common complications of burn injuries. This study was designed to examine the effect of thermal injury on the emptying rate of liquids in conscious rats fitted with stainless steel cannulae in the body of the stomach. In rats with partial-thickness burns emptying of the hyperosmolal saline was found to be delayed (P < 0.5) with respect to control only during the chronic phase of injury. However, full thickness burns delayed hyperosmolal saline emptying in both acute and chronic phases, together with delayed saline emptying in the acute state. Thermal injury did not influence the gastric emptying of peptone and acid solutions, which activate different pathways to delay gastric emptying. Delayed gastric emptying of hyperosmolal solutions may be explained by increased sympathetic and opiatergic nervous activities, resulting in reflex relaxation of gastric smooth muscle. PMID- 7794497 TI - Early basement membrane formation following the grafting of cultured epidermal sheets detached with thermolysin or Dispase. AB - The basement membrane zone is important for graft adhesion and stability. The aim of the present study was to visualize the regeneration of the basement membrane and determine the sequential appearance of its constituents in the early postgrafting period of cultured human epidermal sheets. A keratinocyte single cell suspension, devoid of dermal fibroblast contamination, was obtained from human skin by a two-step tissue digestion method with thermolysin and trypsin. After culturing, epidermal sheets were generated, detached enzymatically by incubating with thermolysin (for 20-30 min) or Dispase (for 45-60 min), and deposited on a muscular graft bed of athymic mice. Immunohistochemistry and ultrastructural analyses were performed on biopsies harvested 2, 4 and 21 days postgrafting. Bullous pemphigoid antigens and laminin were detected at the dermo epidermal junction, showing an almost continuous line 2 days postgrafting. Type IV collagen was generally absent at this time, but it was detected 4 days postgrafting. Type VII collagen was labelled as a discontinuous line of increasing intensity from 2 to 21 days postgrafting. Ultrastructural analysis revealed hemidesmosomes and a discontinuous lamina densa 2 days postgrafting, and a complete basement membrane with a continuous lamina densa, hemidesmosomes and anchoring fibrils 21 days postgrafting. The sequence of appearance of major basement membrane components was similar for cultured sheets detached with thermolysin or Dispase. However, it differed from that of other wound healing models. Results are discussed in terms of the variable keratinocyte migration requirement between various wound healing models. PMID- 7794498 TI - Nosocomial infections in a burn intensive care unit. AB - Although many studies have reviewed burn wound infections (BWIs) in burn patients, few have prospectively surveyed other nosocomial infections. Seriously burned patients are clearly at increased risk for infection due to the nature of the burn injury itself, immunocompromising effects of burn injury, prolonged hospital stays, and invasive diagnostic and therapeutic procedures. Over 6 months, we prospectively reviewed all patients admitted to our burn intensive care unit (BICU) for nosocomial infections. We used standard CDC definitions of nosocomial infections (NIs). Because we had previously documented a high incidence of nosocomial pneumonias in these patients, we were particularly interested in determining risk factors for nosocomial pneumonia. The total census during the study period was 57. There were 40 discharges and deaths. Surveillance demonstrated 36 nosocomial infections in 26 patients, for a total of 90 nosocomial infections per 100 discharges and deaths, or 32.3 NIs/1000 patient days. Infections included 22 pneumonias, 10 urinary tract infections, two bacteraemias, one BWI and one episode of cellulitis. Intubation was strongly associated with nosocomial infection, particularly with pneumonia, BWI and bacteraemia. Sixty per cent of all patients were intubated at some time during their BICU stay, but 88 per cent of those who developed a nosocomial infection were intubated (P < 0.001). Inhalation injury was less significant than intubation in the development of nosocomial infection. All patients who developed pneumonia or a BWI were intubated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794499 TI - Use of hospital statistics to plan preventive strategies for burns in a developing country. AB - This study is based on hospital statistics using 1985 burn patients admitted to Maputo Central Hospital, Maputo, Mozambique, for a period of 42 months (1988-91). On the basis of the results obtained, some suggestions are made for the design of the targets and methods for a preventive strategy for burn injuries in Maputo. Strengthening of preventive measures should occur during the cold season of the year and particularly in the preceding months (March to May). Children under 5 years old would be the main target, particularly the age group 2-3 years. Mothers' and older siblings' education would be the vector and they would be approached through continuing health education activities, regularly carried out at present, and educational programmes in schools. We also propose the use of a simple safety device aimed at preventing burns responsible for the highest lethality. Proposed preventing burns responsible for the highest lethality. Proposed interventions rely on extensive knowledge of the epidemiological parameters influencing the occurrence of burns severe enough to warrant admission to hospital. The beneficial impact of these interventions on hospital workload and economy would probably overcome costs for its implementation. PMID- 7794500 TI - Alcohol and drug abuse in burn injuries. AB - Two studies are described in this paper. In the first study 225 acutely, severely burned patients were retrospectively investigated as to admission blood alcohol level and history of chronic alcohol abuse. The influence of further risk factors, circumstances and therapeutic data was studied, in particular the influence of gender, full-thickness burns, smoke inhalation injury, smoking, length of total and ICU stay, and suicide attempt. The 70 patients with positive blood alcohol levels on admission had a significantly higher fatality rate (31.5 per cent) in comparison with the 18.1 per cent fatality rate of patients with a negative blood alcohol level. Both groups had nearly identical mean TBSA and mean age. Chronic alcohol abuse was noted in 59 patients. These patients were found to have a higher fatality rate (31.4 per cent, 22/70) compared with that of patients without a history of chronic alcohol abuse who had an overall fatality rate of 18.1 per cent (28/155). No significant difference was found between non intoxicated and acutely intoxicated alcoholics (31.4 vs 29.3 per cent). Our conclusion is that intake of alcohol before burn injury represents an independent risk factor. The second study was a prospective study of 16 consecutively admitted burn patients, who were evaluated for both drug and alcohol intake. Five patients had positive drug levels and five had positive alcohol levels. Five patients had a history of chronic drug and/or alcohol abuse. This incidence of alcohol and drug abuse supports the findings of our retrospective study. PMID- 7794501 TI - Burns in octogenarians. AB - With the aim of identifying patterns of burn injury, remediable risk factors, and policies in the overall surgical and medical management a retrospective review of 111 octogenarian burn victims admitted between 1983 and 1993 is presented. The mean age was 84 years, with the mean percentage body surface area burned (%BSAB) being 9.6 per cent (range 0.5-65 per cent). Contrary to expectations, the annual incidence appears to be declining, the possible reasons for which are discussed. Surgery was required in 69 patients; in 11 this was performed within 1 week of injury. When compared to the more traditional delayed surgical approach, early surgery conveyed no benefits in either mortality (early group, 18 per cent; delayed group, 13 per cent) or length of hospital stay (early group survivors, 38 days; delayed group survivors, 42 days). Medical and social problems were very common and led to an often difficult and frequently prolonged rehabilitation, with the mean length of hospital stay for all patients being 29 days. The mortality of the whole group was 26 per cent, the patients on average faring better than their predicted mortalities as derived using either the Baux index, the Bull table or the Abbreviated Burn Severity Score. PMID- 7794502 TI - Reducing the burn risk to elderly persons living in residential care. AB - A 45-month retrospective analysis of 70 geriatric burn admissions to the Welsh Regional Burns and Plastics Unit highlighted 13 (18.6 per cent) injuries that occurred whilst the patient was in residential care (six residential care homes, seven nursing homes). The mean age overall was 83 years. The residential care patients had a TBSA of 12.5 per cent with a mortality of 46 per cent, whilst the group living in the community had a TBSA of 8.63 per cent with a mortality of 14 per cent. These results were not statistically comparable due to the unequal population grouping. The cause of injury in the residential group included five hot water scalds, six radiator contact burns, one flame burn and one flash burn. All 13 patients were found to have such severe dementia that they were unable to give a reliable history. In the majority of patients a lack of supervision was in part responsible. Some basic measures are presented that could reduce the incidence of accidental burn injury in this vulnerable group of the population. PMID- 7794503 TI - The use of tissue expansion in children with burns of the head and neck. AB - The outcome of 25 children who underwent reconstruction of the head and neck with tissue expanders is described. Fourteen boys and 11 girls with a mean age of 6.2 years (range 3-11 years) had 36 tissue expanders inserted. Five of the expanders extruded and five children suffered other expander-related complications. The best aesthetic results were achieved in the scalp and the poorest results occurred where expanded neck skin was transposed into the face. Tissue expansion is a useful method for reconstruction of the head and neck in burned children. However patients require careful selection in order to achieve optimal results. Meticulous attention to detail is required to reduce the incidence of complications. PMID- 7794505 TI - A simple guide to burn epidemiology. International Society for Burn Injuries in collaboration with the World Health Organization. PMID- 7794504 TI - A metabolic complication of severe burns. AB - A 32-year-old male was referred to intensive care with possible respiratory sepsis 15 days after sustaining 73 per cent TBSA electrical burns. Investigation revealed previously undiagnosed hyperosmolar non-ketotic diabetic coma. The aetiology, pathogenesis and management of this recognized complication of major burns is discussed. An interesting feature of this case is recovery from 73 per cent burns, severe hyperosmolar non-ketotic diabetic coma and a serum osmolality of 429 mosmol/kg, each of which carry a high mortality probability. PMID- 7794506 TI - A simple guide to burn treatment. International Society for Burn Injuries in collaboration with the World Health Organization. PMID- 7794507 TI - A simple guide to burn prevention. International Society for Burn Injuries in collaboration with the World Health Organization. PMID- 7794508 TI - A simple guide to the burn registry. International Society for Burn Injuries in collaboration with the World Health Organization. PMID- 7794509 TI - Survival in non-immune hydrops fetalis without malformation or chromosomal abnormalities after invasive treatment. AB - The aim of the study was to determine the outcome of fetuses with non-immune hydrops (NIH) following modern invasive investigation and therapy. This prospectively planned observational study involved 23 women with singleton fetuses in whom a diagnosis of NIH was made in our fetal medicine unit in 1 year. After investigation and counselling 15 of the 23 women opted for termination of pregnancy (10 chromosomal and 5 structural abnormalities) and there was 1 intrauterine fetal death before therapy was attempted. One case with diaphragmatic hernia was treated with shunting which successfully reversed the hydrops, the pregnancy continued to term, the malformation was surgically corrected but the neonate died from pulmonary hypoplasia. In the remaining 6 cases structural and chromosomal abnormalities were excluded. One had amniotic fluid drainage for polyhydramnios but despite this delivered at 30 weeks' gestation and the neonate died on day 5. The remaining 5 cases had fetal therapy between 22 and 32 weeks' gestation (4 shunt insertions, 1 blood transfusion) and in all the hydrops reversed and the pregnancy continued to at least 35 weeks' gestation. All 5 neonates were discharged from hospital alive and well. Fetal therapy in cases of NIH with normal structure and karyotype was associated with a very good outcome. Giving a uniform poor prognosis is no longer justified because if other fetal abnormalities are excluded, in utero treatment, reversal of the hydrops and survival are often possible. We recommend urgent referral of these cases to a fetal medicine unit. PMID- 7794510 TI - Ominous normalization of middle cerebral artery flow velocity waveforms preceding fetal death: case report. AB - The loss of middle cerebral artery compensatory vasodilation appears to be ominous in fetuses with absent end-diastolic umbilical waveforms. The authors report a case with a loss of the 'brain-sparing effect' 24 h before fetal death. Current pathophysiological explanations are discussed. PMID- 7794511 TI - Are 'notched' uterine arterial waveforms of prognostic value for hypertensive and growth disorders of pregnancy? AB - In a case-control controlled study of 86 women identified as having bilaterally 'notched' uterine arterial waveform patterns at 18 weeks, the presence of bilateral 'notched' uterine arterial waveforms at that time was associated with the subsequent development of hypertension and small-for-gestational-age infants, but the predictive value was poor. For those women in whom the bilateral uterine 'notches' were observed to persist to 24 weeks, the relative risk of developing proteinuric hypertension increased 14 times, and in these women the positive predictive value for the subsequent development of hypertension increased to 58.6% when compared with their matched controls. The identification of women with persistent bilateral uterine 'notches' provides a means of identifying women at significant risk of hypertensive and growth disorders at a stage when therapeutic intervention aimed at limiting the severity of the disease and its associated complications could be commenced. PMID- 7794512 TI - Iatrogenic gastroschisis decreases pulmonary hypoplasia in an ovine congenital diaphragmatic hernia model. AB - Pulmonary hypoplasia is a major problem in infants with congenital diaphragmatic hernia. Intrauterine reparative procedures are associated with a high complication rate. The development of less complex operations to reduce the degree of fetal lung hypoplasia may improve neonatal survival. Our objective was to investigate the effectiveness of an iatrogenic gastroschisis in reducing fetal pulmonary hypoplasia in a sheep model with an artificially created diaphragmatic hernia. A left-sided diaphragmatic hernia (Bochdalek type) was created at 75 days' gestation in an ovine fetal model during the pseudoglandular phase of lung development. At 110 days' gestational age, a left-sided gastroschisis was created by excising part of the lower abdominal wall and buttressing the opening with a rubber ring. The fetus remained in utero until 135 days' gestation, at which time it was sacrificed for autopsy. Histopathologic and morphometric studies were performed on the lungs. Ten animals had creation of a diaphragmatic hernia. Four underwent the second surgery to create a gastroschisis. One animal completed the entire protocol, 3 fetuses aborted after the second surgery. Autopsy confirmed effective decompression of the herniated abdominal contents from the chest into the amniotic cavity in all 4 cases. The lungs of the animal that completed the protocol were appropriately developed, while those fetuses that died soon after gastroschisis creation had severe pulmonary hypoplasia, mainly involving the left lung. Artificially induced diaphragmatic hernia, in the ovine fetus, causes severe pulmonary hypoplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794513 TI - In utero surfactant administration to preterm human fetuses using endoscopy. AB - Our purpose was to assess the feasibility of the endoscopic delivery of surfactant directly to the fetus during active preterm labor. A gas-sterilized intraoperative fiberscope was introduced through the cervical canal into the amniotic cavity after spontaneous rupture of membranes during preterm labor in 3 patients. The flexible fiberscope was inserted under constant endoscopic visual control to avoid possible trauma to the fetus and the mother. Surfactant was injected into the mouths of 3 preterms fetuses through a catheter placed through the biopsy channel of the fiberscope. Fetal heart rate tracings as well as neonatal and maternal outcome are reported for each case. In utero surfactant placement was successful in each case. The fetal heart rate remained normal throughout the procedure. No maternal or neonatal complications/infections were detected. Our preliminary experience indicates that in utero endoscopic delivery of surfactant to a preterm human fetus is feasible. The usefulness of intrapartum endoscopy in the prophylactic administration of surfactant directly to the fetus, prior to the first breath, has to be assessed in a prospective controlled study. PMID- 7794514 TI - Fetal hepatosplenomegaly associated with transient myeloproliferative disorder in trisomy 21. AB - The in utero diagnosis of fetal myeloproliferative disease was made by cordocentesis following the ultrasound appearance of fetal hepatosplenomegaly and mild hydrops. The 2 fetuses reported both had leukocyte counts greater than 75,000/mm3 with a predominance of blast forms. In both cases the karyotype revealed trisomy 21. PMID- 7794515 TI - A case of nondiabetic macrosomia with Simpson-Golabi-Behmel syndrome: antenatal sonographic findings. AB - The incidence of macrosomic infants weighing 5,000 g or more is rare. We experienced a case of nondiabetic macrosomia, in which the fetus weighed more than 5,000 g. The newborn was diagnosed as having Simpson-Golabi-Behmel syndrome. We discuss antenatal ultrasonographic findings in the case. PMID- 7794516 TI - Comment on the article by J. Wisser et al. Neonatal hemochromatosis: a rare cause of nonimmune hydrops fetalis and fetal anemia. [Fetal Diagn Ther 1993;8:273-278]. PMID- 7794517 TI - In utero fetal muscle biopsy alters diagnosis and carrier risks in Duchenne and Becker muscular dystrophy. AB - OBJECTIVES: We have previously shown that Duchenne muscular dystrophy (DMD) can be diagnosed by fetal muscle biopsy and immunohistochemical staining showing the absence of dystrophin. In Becker muscular dystrophy (BMD), there is a variable dystrophin staining pattern. STUDY DESIGN: A 26-year-old, gravida 5, para 1, SAB 2, VIP 1, white female had a son with the diagnosis of BMD, with no other affected family members. In the current pregnancy, the male fetus inherited the same X chromosome. RESULTS: Fetal muscle biopsy revealed no dystrophin, consistent with the diagnosis of DMD, prompting re-analysis of the sibling whose diagnosis was then changed to DMD. CONCLUSIONS: Molecular techniques in prenatal diagnosis in this case not only led to the diagnosis of a severe disorder in the current pregnancy, but changed the diagnosis in another child, allowing for more appropriate counseling of this couple. PMID- 7794518 TI - Very low maternal serum unconjugated estriol and prenatal diagnosis of steroid sulfatase deficiency. AB - Twenty-four women out of 7,875 pregnant women who enrolled in a prenatal screening program showed extremely low levels of unconjugated estriol (< 0.15 MOM). In 19 cases, intrauterine fetal death was reported. In 1 case anencephalus was detected. In the remaining 4 cases apparently normal healthy babies (1 female and 3 males) were born following uneventful pregnancies. Physical examination of the 3 boys at 4-6 weeks revealed mild ichthyosis compatible with the X-linked type. Two of them had a positive family history of X-linked ichthyosis. The examination of the girl did not reveal any significant findings. In both cases in which amniocentesis was performed, low levels of steroid sulfatase and arylsulfatase C were found. The prevalence of X-linked ichthyosis in this study is higher than previously reported, i.e. 1:1,300 males. Our results suggest that the prenatal screening program for neural tube defects and for Down's syndrome is useful for the prenatal detection of X-linked ichthyosis as well. These results are in accordance with two recent reports. The implications regarding genetic counseling are discussed. PMID- 7794519 TI - Needle embryofetoscopy and early prenatal diagnosis. AB - Needle embroyfetoscopy (NEF) permits direct visualization of the embryo/fetus with a specially designed 16-gauge double-barrel instrument sheath which is passed transabdominally into the amniotic cavity. We report the case of a woman with a MSAFP of 2.5 MOM who had declined amniocentesis. A targeted ultrasound examination of the spine revealed what appeared to be spina bifida in the lumbar sacral segments from L2 to S1. The mother elected to undergo NEF at 15 weeks gestation, which was successfully performed and revealed no evidence of a neural tube defect. NEF has a tremendous potential for both early prenatal diagnosis, and possibly fetal treatment. PMID- 7794520 TI - Fetal responses to inadvertent contact with the needle during amniocentesis. AB - Fetal responses in 7 cases of mid-trimester amniocentesis, complicated by inadvertent contact between the amniocentesis needle and fetal parts, were analyzed by retrospective videotape review. The incidence of inadvertent needle contact with the fetus was 0.4% (7 of 1,458). Responses included brisk withdrawal of the 'involved' small part in all cases, with the exception of a fetus with lumbosacral meningomyelocele, which failed to withdraw the foot upon direct contact with the needle. Neurologic examination was normal in all neonates except for one with meningomyelocele whose defect was at the L3-L5 level. This patient exhibited paralysis of intrinsic foot muscles and hip extensors. Surgical closure of the defect was performed 12 h after birth. At 2 years of age, no significant improvement in this patient's neurologic condition was noted. Further research is needed to assess the validity of the response to needle contact as a predictor of neonatal neurologic compromise. PMID- 7794522 TI - Midtrimester thoracoamniotic shunting for the treatment of fetal hydrops. AB - The management of fetal hydrops in the second trimester is changing as the underlying etiologies are better understood. We report a case which was diagnosed at 18 weeks gestation. There was no underlying anatomical abnormality. Fetal blood sampling confirmed a normal karyotype and there was no evidence of fetal infection. Bilateral thoracocentesis and paracentesis caused temporary improvement of the fetal condition but subsequent fluid reaccumulation was noted within the left pleural cavity. A pleuroamniotic shunt inserted at 22 weeks caused permanent resolution of the hydrops. The infant was normal at 1-year follow-up. PMID- 7794521 TI - Fetal serum erythropoietin in twin pregnancies with discordant growth. A clue for the prenatal diagnosis of monochorionic twins with vascular communications. AB - Ten sets of diamniotic twins with discordant fetal growth (ultrasonographic estimated fetal weight difference > 25%) and abnormal amniotic fluid volume were assessed for fetal serum erythropoietin concentration (Epo). All 20 fetuses had a percutaneous umbilical blood sampling performed between 21 and 33 weeks gestation. Three sets of twins were dichorionic while 7 sets were monochorionic. In these 7 monochorionic sets a vascular communication between twins was demonstrated prenatally and postnatally. From 24 weeks gestation the smaller twin of the dichorionic group had a higher serum Epo than its larger cotwin; the larger cotwin's serum Epo was within normal limits for singleton controls. All fetuses with documented vascular communications had higher serum Epo concentration than singleton controls. These findings suggest that determination of fetal serum Epo in the large cotwin may be a clue to the diagnosis of vascular communications between twins with discordant growth. PMID- 7794523 TI - Predictive value of pleural effusions in fetal hydrops. AB - Twenty-eight cases of fetal hydrops are reported. A diverse aetiology was found. Fetal therapy was undertaken in 12 (42.9%). The overall survival rate was 36.8% (excluding elective terminations). However, when normal fetuses presenting from 20 weeks were considered, the survival rate was 64%. The results were combined with those of two other studies (making a total of 182 cases with fetal hydrops) to ascertain the value of pleural effusions in predicting outcome in such cases. In the 143 cases that did not end in a therapeutic termination of pregnancy, fetal pleural effusions predicted death (fetal or neonatal) with a sensitivity of 67%, a specificity of 53%, a positive predictive power of 68%, a negative predictive power of 52% and an overall accuracy of 62%. PMID- 7794524 TI - In vitro amyloid fibril formation from alpha 1-antitrypsin. AB - We have previously shown that the interaction between alpha 1-antitrypsin (AAT) and lithocholic acid (LA) results in changes of AAT properties leading to its polymerization and inactivation. To define the structural rearrangements of AAT induced by such interaction, we studied the in vitro binding between AAT and LA at molar ratio 1:5 for varying time intervals at a physiological pH. Complex formation was shown by electrophoretic techniques and autoradiography. Studies of the AAT in complex with LA by using far-UV spectra circular dichroism and fluorescence measurements indicated an increase of beta-structure of AAT and pronounced changes in surroundings of the chromophores. In addition, complexed AAT showed increase in thermal stability, compatible with that after proteolytic cleavage. Characterization of the AAT-LA complexes by Congo red binding, polarization and negative staining electron microscopy provided clear evidence that AAT, under chosen experimental conditions, can self-assemble into amyloid fibrils, compatible with accepted models of fibrillar structures. This propensity of AAT to form stable beta-structures in a hydrophobic surrounding may contribute to improved characterization of various amyloid deposits occurring in vivo and be a guide for understanding details of structure-function relationships in the intact AAT-molecule. PMID- 7794526 TI - Primary structure of the thermosome from Thermoplasma acidophilum. AB - The thermosome, a chaperonin from the archaebacterium Thermoplasma acidophilum, consists of two subunits (M(r) 58,000 and 60,000) which assemble into a cylindrical complex of pseudo eight-fold rotational symmetry. The sequences of the two subunits are approximately 60% identical to each other and to TF55 from Sulfolobus shibatae, and are 30-40% identical to the subunits of the TCP1 containing ring complex (TRiC) from the eukaryotic cytosol. A dendrogram of this family of chaperonins contains eight eukaryotic branches of TRiC subunits and one archaebacterial branch of thermosome subunits. Alignment of thermosome/TRiC sequences with eubacterial and eukaryotic Hsp60 sequences reveals a statistically significant similarity in two large N- and C-terminal blocks of sequence. Based on this alignment and on the recently published crystal structure of GroEL, we propose that subunits of the thermosome/TRiC family of chaperonins have a similar equatorial domain and overall domain topology as GroEL but differ in the structure of the apical domain. PMID- 7794525 TI - Purification and characterisation of pyruvate decarboxylase from pea seeds (Pisum sativum cv. Miko). AB - Pyruvate decarboxylase (PDC) was purified from pea seeds. The catalytically active holoenzyme is an oligomer of two types of subunits with molecular masses of about 65 kDa and 68 kDa, respectively. The active enzyme is a mixture of tetramers, octamers and even higher oligomers. These differences in the quaternary structure compared with PDC from yeast (tetramer) do not result in a different kinetic behaviour. The activity of pea PDC as well as that of yeast PDC is regulated by its substrate pyruvate resulting in a sigmoid shape of the v/S plot. At the optimum pH of 6.0 a S0.5-value of 1 mM pyruvate is found that increases with rising pH and increasing concentrations of phosphate. The substrate analogue activator pyruvamide activates the enzyme resulting in a hyperbolic v/S-plot. The stability of PDC from pea seeds in solution is about one order of magnitude higher than that of yeast PDC. Despite the described similarities of the two enzymes no significant cross reactivity of the anti-pea PDC antibody with the enzyme from yeast occurs. PMID- 7794527 TI - Studies on S14 protein from Thermus thermophilus possessing zinc finger-like motifs. AB - The amino acid sequence of the ribosomal protein S14 of Thermus thermophilus has been determined both by automated sequence analysis of the intact protein as well as by DNA sequence analysis of the gene. The carboxy-terminal region was verified by both amino acid sequence analysis of the carboxy-terminal peptide produced after Glu-C digestion and by DNA sequence analysis. The protein contains 60 amino acid residues with a calculated molecular weight of 7008. The most extensive homology is observed in the carboxy-terminal regions of all S14 proteins compared. Interestingly, the carboxy-terminal region of most S14 proteins of all species studied so far, form zinc-finger domains in the variety of C2-C2 form. PMID- 7794528 TI - Mammalian cysteine protease inhibitors: biochemical properties and possible roles in tumor progression. AB - The endogenous cysteine protease inhibitors represent the final level at which cysteine protease activity can be regulated. These inhibitors are subdivided into three families (stefins, cystatins and kininogens) which belong to the protein superfamily, cystatins. Cystatins do not form a covalent bond with cysteine proteases, but instead cover the active site cleft blocking access to the active site. The most important biochemical characteristics of the cystatins are described in the first part of this review. Alterations in the balance between endogenous cysteine protease inhibitors and cysteine proteases have been postulated to contribute to malignant progression. A few studies have demonstrated the enrichment of cysteine protease inhibitor activity in the membrane fraction of tumors/cells. Evidence is accumulating that an inverse correlation exists between the level of stefin A, one of the cysteine protease inhibitors, and malignant progression. Stefin A has even been hypothesized to be a tumor suppressor. However, additional studies are necessary in order to prove functional roles for the individual cysteine protease inhibitors in tumor growth and progression. PMID- 7794529 TI - Determination of peptide regions exposed at the surface of the bacterial ribosome with antibodies against synthetic peptides. AB - We synthesized six peptides corresponding to regions that are predicted to be surface-exposed of the following ribosomal proteins: protein L2, positions (D263 K272); protein L5, positions (I136-G150); protein L25, positions (Q75-D90); protein S3, positions (Q222-K232) derived from Escherichia coli; and protein L2, positions (K257-K275), and protein S3, positions (R130-T150) from Bacillus stearothermophilus. These peptides were employed to raise ribosomal protein-cross reactive antibodies. The anti-peptide antisera reacted specifically with their parent proteins, as demonstrated by immunoblotting experiments. In a competition assay proteins L2 from E. coli and B. stearothermophilus as well as proteins L5 and L25 from E. coli were found to be accessible to the respective anti-peptide antibodies in the 50S subunits, but not in 70S ribosomes, proving their location at the 50S interface which is covered by the 30S subunit in the 70S complex. Two of the anti-peptide antisera directed against sequences deduced from protein S3 of E. coli and B. stearothermophilus reacted with 30S subunits as well as with 70S ribosomes, demonstrating their location at the backside, which is exposed to solvent. Thus, by the strategy applied specific short peptide stretches were located at the surface of the ribosome. PMID- 7794531 TI - Development of a polymer-enzyme immunoassay method and its application. AB - Both poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide)-antibody (PINP Ab)-labelled enzyme adhered quickly and tightly to cellulose acetate/nitrate membrane either below (less efficiently) or above (more efficiently) the lower critical solution temperature, and the retention of PINP-Ab on the membrane increased over 30-fold when compared with the unconjugated Ab. These characteristics were used to develop a novel polymer-enzyme-linked immunoassay method: homogeneous antigen-antibody immune-complexation reaction and a heterogeneous separation process. By using a simple horseradish-peroxidase labelled antibody as a probe, we applied this method to the detection of human serum hepatitis B surface antigen (HBsAg). This immunoassay system can detect as little as 1 ng/ml of HBsAg. The advantages of this method are: (a) fast homogeneous immune complexation; (b) a rapid heterogeneous separation process; (c) high sensitivity; and (d) low non-specific background. PMID- 7794530 TI - Ras-GTP regulation is not altered in cultured melanocytes with reduced levels of neurofibromin derived from patients with neurofibromatosis 1 (NF1). AB - As derivatives of the neural crest, epidermal melanocytes are supposed to be clinically affected by NF1 gene defects. The NF1 gene shares sequence homology with the p120 GTPase activating protein (p120-GAP) and neurofibromin has been shown to participate in Ras-regulation. By immunoprecipitation and Western blotting, neurofibromin was found to be expressed in melanocytes from the unaffected skin and cafe au lait macules of NF1 patients, but the intensity of the neurofibromin band was decreased compared to control cultures. The Ras GTP/Ras-GDP ratios of NF1 derived melanocyte cultures were comparable to those derived from healthy donors. Furthermore, the total GAP-activity of cell lysates was not altered in NF1 melanocyte cultures compared to controls. However, lysates of proliferating melanocytes, both from NF1 patients and from healthy donors, showed an about 2-fold higher GAP-activity than poorly growing cells. Neurofibromin contributed approximately one third of total GAP-activity, in both control and NF1 melanocytes, indicating that it is not the major regulator of Ras in these cells. These results suggest that the function of neurofibromin in melanocytes is not limited to regulation of Ras activity. PMID- 7794532 TI - Isolation from bovine haemoglobin of a peptide that might be used as a potential hydrophobic photosensitizer carrier. AB - The isolation of a peptic hydrolysate and of a pure peptide from bovine haemoglobin is described. These peptides were used to solubilize an insoluble photosensitizer in order to study their utilization as a carrier for photochemotherapy. Protoporphyrin IX was used as a model of an insoluble photosensitizer. Solubilization of protoporphyrin IX was first performed with the total haemoglobin hydrolysate, then with peptide fractions, and finally with a pure peptide isolated from this fraction by reversed-phase HPLC. The molecular mass and the primary structure of the pure peptide were determined by fast-atom bombardment and tandem MS (molecular mass 1648 Da). The singlet oxygen quantum yield of the protoporphyrin IX-peptide complex was determined. PMID- 7794533 TI - Recombinant human acetylcholinesterase expressed in Escherichia coli: refolding, purification and characterization. AB - A large-scale preparation of a recombinant human acetylcholinesterase (rhAChE) mutant harbouring a CyS580-->Ser substitution, expressed in Escherichia coli, was refolded following solubilization of the inclusion bodies. Refolded active rhAChE was purified by DEAE-Sepharose and affinity chromatography to apparent homogeneity with a specific activity (4572 units/mg) similar to that of erythrocyte AChE. The stability of the purified enzyme at 22-37 degrees C was dependent on the presence of 0.5 mg/ml BSA, and the optimum pH for stability was 9.0. rhAChE has a UV-absorbance spectrum typical of a tryptophan-rich protein, with a distinct shoulder at 290 nm and a high absorption coefficient at 280 nm (epsilon 1% = 23.1). The tryptophan residues in active rhAChE are located in an apolar environment, characteristic of a globular molecule. The difference in amino acid composition between red-blood-cell-derived and recombinant hAChE is probably reflected in their different pI values, namely 5.5-5.8 and 4.6-5.2 respectively. The CD spectrum of rhAChE is typical for an alpha/beta protein, indicating 39% alpha-helix and 22% beta-sheet. This secondary structure is similar to that determined for the Torpedo (electric fish) AChE, by both CD and X ray crystallography. On the other hand, a purified misfolded and inactive molecule displays a decrease in alpha-helical content to 24%, accompanied by an increase in beta-sheet up to 42%, indicative of extensive changes in the conformation of the protein. On the whole, the recombinant enzyme has been refolded into a native-like conformation possessing full activity, and is thus similar to the naturally occurring red-blood-cell-derived hAChE. PMID- 7794534 TI - Properties of laccase isoenzymes produced by the basidiomycete Ceriporiopsis subvermispora. AB - Laccase is one of the ligninolytic enzymes found in liquid cultures of the fungus Ceriporiopsis subvermispora in defined medium. As an approach to a clarification of the role of laccases during the attack on lignin by the fungus, the enzyme has been characterized further. The levels of this phenol oxidase increase 2-fold in the presence of p-anisidine and are severely affected when addition of either Mn(II) or Cu(II) ions to the medium is omitted. Isoelectrofocusing allowed the resolution of two laccase isoenzymes, with pIs of 3.65 and 3.59. In rich medium, laccase activity is 10-fold higher than in salt medium, and it is not affected by the external addition of p-anisidine or Mn(II). Four isoenzymes were detected in these cultures, with pIs between 3.76 and 3.60. In a wheat bran medium, four isoenzymes with pIs in the range 3.63-3.46, plus a fifth isoenzyme of high pI (4.82), were also identified. The absorption spectrum of a pool containing the four isoenzymes from rich medium shows a maximum at 600 nm, typical of laccase possessing a type I copper atom. The molecular mass of the isoenzyme with pI 3.60 is 79 kDa, as determined by SDS/PAGE. Upon treatment with endoglycosidase F, the molecular mass of this isoform decreases to 63 kDa, indicating a high degree of glycosylation. Substrate specificity studies conducted with the four isoenzymes from rich medium and a combination of isoenzymes from salt medium showed marked differences among them. The amino-terminal sequences (24 residues) of three isoenzymes isolated from rich medium were determined. Two of them are identical, whereas the third one differs from these in three amino acid residues. The consensus sequence reveals clear homology with laccases from other microorganisms. PMID- 7794535 TI - Preparation and characteristics of magnetite-labelled antibody with the use of poly(ethylene glycol) derivatives. AB - With a view to the application of magnetic particles in cancer thermotherapy (hyperthermia), methods of preparing a bio-applicable magnetite with targeting activity towards cancer cells were investigated, and the properties of the material examined. Poly(ethylene glycol) (PEG)-magnetite consisting of magnetite (Fe3O4) and PEG with terminal carboxy or amino groups was prepared. Monoclonal antibody was then immobilized covalently on to the PEG-magnetite. Among three different immobilization methods employed, the highest immobilization density of 492 mg of protein/g of PEG-magnetite was achieved by using water-soluble carbodi imide. However, with respect to residual antibody activity, only the method in which IgG sugar chains were oxidized to give aldehyde groups for coupling to N terminal PEG-magnetite was satisfactory, with about 60% of the activity surviving. The immobilization density by this method (109 mg of protein/g of PEG magnetite) was also sufficiently high. The product, termed magnetite-labelled antibody, was of sub-micrometre size and showed easy magnetophoresis. It was further elucidated that cancer-specific magnetite-labelled antibody bound to cancer cells at an amount of 50 mg of magnetite/cm3 of cells. The PEG-magnetite generates heat at an evolution rate of 31.5 W/g, and the amount adsorbed to the cells was calculated to be high enough to heat a tumour 1 cm in diameter to more than 42 degrees C in 30 s under an alternating magnetic field [at an intensity of 572 Oe (approx. 45.5 kA/m) and a frequency of 240 kHz]. This magnetite-labelled antibody is expected to be applicable clinically as a therapeutic agent for the induction of hyperthermia. PMID- 7794536 TI - Transgenic models of HIV-1. AB - Transgenic technology has been very successful at providing insights into possible processes involved in HIV-induced pathogenesis. The availability of these small animal models for the study of HIV-related syndromes including KS, epidermal proliferative lesions, HIV-associated nephropathy, AIDS-related growth failure and cachexia may well facilitate the development of novel therapies for these complications. Other phenotypes created in mice, such as cataracts and hepatic cancer [59], may not have human analogies but may still provide insight into pathogenesis. Thus, transgenic models have already provided resources to study many manifestations of AIDS and others are likely to be developed. The optimal strategy for designing future transgenic animals, however, is less clear. No transgenic mouse model has been generated to date that will provide an avenue for vaccine development. This advance awaits the further discovery of the host factors that facilitate the virus replicative cycle in humans and a better understanding of these pathways in the mouse. For the development of molecular based therapy, however, the currently available models may well be adequate to test molecular inhibitors of transcription [7,60,61] and post-transcriptional processing of viral mRNA [62]. Whether single or multigenic constructs under the control of the LTR are better or worse for this purpose is a debatable issue. Transgenic technology may yet make an additional contribution to the development of molecular therapy for AIDS. The best method of demonstrating that a gene therapeutic strategy is safe to administer to patients has not been determined. By introducing potentially therapeutic constructs into mice as transgenes, their safety can be assessed in many different cell types in vivo, analogous to toxicological testing in rodents for systemically administered drugs. Thus, transgenic technology has already provided insights into the pathogenesis of HIV 1. While it has not yet proven its utility for vaccine development, transgenic technology holds the promise of being an active participant in the development of both safe and effective gene therapy approaches for the treatment of AIDS. PMID- 7794537 TI - Rates of p24 antigenemia and viral isolation in comparable white and black HIV infected subjects. Military Medical Consortium for Applied Retroviral Research. AB - OBJECTIVE: To determine the relative frequencies of HIV-1 p24 antigen and culture positivity in white and black patients. DESIGN: Volunteers in the US military's HIV natural history study were 46% white, 44% black, 7% Hispanic and 3% other. Focusing on the comparable groups of whites and blacks, a retrospective analysis was performed of the results of virologic assays collected over a 2-year period. METHODS: p24 antigen was quantitated in sera with and without immune complex dissociation (ICD); viral isolation was performed by coculture of peripheral blood mononuclear cells. RESULTS: Results of the two virologic assays were very similar in the two racial groups, both overall and after stratification by CD4 cell count. As reported previously, the concentration of serum immunoglobulin G was found to be greater in black than white subjects. In contrast to results with ICD, sera tested without ICD resulted in differing (higher) rates of antigenemia in whites than blacks (P = 0.002). CONCLUSIONS: The frequencies of p24 antigen and culture positivity were found to be independent of race. Previously observed racial differences in antigen positivity were likely to be due to more extensive antibody binding in blacks than in whites. PMID- 7794538 TI - Unidirectional budding of HIV-1 at the site of cell-to-cell contact is associated with co-polarization of intercellular adhesion molecules and HIV-1 viral matrix protein. AB - OBJECTIVES: To explore the possibility that HIV-1 budding and cellular adhesion molecules co-polarize at cell-to-cell contact sites. To investigate the incorporation of host-cell-derived adhesion molecules into HIV-1. METHODS: The cellular sites involved in HIV-1 budding were examined by transmission electron microscopy. Single and double immunocytochemistry staining was used to evaluate the cellular distribution of the viral matrix protein and adhesion molecules. Quantitative flow cytometry was used to measure the cellular expression of adhesion molecules. An immunocapture technique was used to measure the presence of cell-derived proteins on HIV-1. The captured virus was measured by a p24 antigen assay. The infectivity of virus captured by monoclonal antibodies was tested by measuring the virus antigen yield in supernatants after the addition of sensitive cells. RESULTS: Released and budding HIV-1 was mainly localized at the cell-to-cell contact regions. This feature was consistent with a polarized staining for the virus matrix protein p18 at cell-to-cell contact regions. Intercellular adhesion molecules (ICAM)-1 in HIV-1-infected cells were polarized on both isolated cells and syncytia, co-localizing with HIV-1 matrix protein. HIV 1 incorporated all the adhesion molecules expressed by the host cells, although without quantitative correlation with their cellular expression. CONCLUSIONS: HIV 1 is released at cell-to-cell membrane contact sites. Both ICAM-1 and virus matrix protein co-polarized on isolated cells and syncytia at the sites involved in the recruitment of uninfected cells. The impressive concentration of ICAM at cell sites where most virions are released may account for the acquisition of these membrane proteins by the HIV-1 progeny, and may be important for the cell mediated spread. PMID- 7794539 TI - High resolution analysis of HIV-1 quasispecies in the brain. AB - OBJECTIVE: To characterize HIV-1 quasispecies at high resolution to determine the in vivo sequence heterogeneity of virus infecting the brain. METHODS: A 1 kilobase region of the envelope gene, which includes the five hypervariable regions, was amplified by polymerase chain reaction (PCR) using DNA obtained from brain tissue of an HIV-1-infected patient. PCR products were cloned and 50 clones sequenced. RESULTS: Thirty-nine unique nucleotide sequences producing 35 protein variants were found. A consensus sequence was identified along with three distinct subtypes, each present at a level of 12%. The sequence variation from the consensus was 0.1-2.1% at the nucleotide level with hypermutation and recombination responsible for the highest diversity. Sequence heterogeneity resulted in both the creation and the elimination of N-linked glycosylation sites. Only nine clones differed from the consensus sequence in the V3 loop. No inactivating mutations were found. CONCLUSIONS: HIV-1 proviruses found in the brain generally demonstrate a low level of genetic variability in env. However, genomes that vary considerably from the predominant species can be present at significant levels. This observation may be of importance for understanding viral pathogenesis in the central nervous system. PMID- 7794541 TI - Diarrhoea in HIV-infected patients: no evidence of cytokine-mediated inflammation in jejunal mucosa. AB - OBJECTIVE: To determine whether a mucosal cytokine-mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV-infected patients. DESIGN: Prospective study. METHODS: Jejunal biopsies were obtained from HIV-infected patients with diarrhoea. Controls were HIV-infected and HIV-seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)-1 beta, IL-6, IL-8, IL-10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL-2 receptor (sIL-2R) were assessed in the homogenates and in the supernatants by sandwich enzyme-linked immunosorbent or enzyme-linked binding assays. The cytokine receptors were also measured in serum. RESULTS: Six HIV infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV-seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL-6 and IL-8 levels were higher in HIV-infected patients with diarrhoea of unknown origin than in HIV-seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post-culture supernatant sTNFR p55 and p75 levels existed between the HIV-infected patients with or without diarrhoea. sTNFR, IL-1 beta, IL 10 and the sIL-2R were only detected in low amounts or not at all, and were equally distributed among all patient groups. CONCLUSIONS: This study indicates that mucosal cytokine-mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV-infected patients. These results do not support the use of immunomodulatory therapy in these patients. PMID- 7794540 TI - Frequency of early in utero HIV-1 infection: a blind DNA polymerase chain reaction study on 100 fetal thymuses. AB - OBJECTIVE: To estimate the prevalence of in utero transmission of HIV-1 through the second trimester. MATERIAL AND METHODS: One hundred consecutive, unselected, intact fetuses, beyond 15 weeks gestational age (mean, 22.4 weeks) were studied. These were obtained following spontaneous intrauterine deaths (n = 4), miscarriages (n = 4), and elective mid-trimester terminations (n = 92), eight of which were fetuses with malformations from HIV-1-positive pregnancies. Coded DNA extracts from the fetal thymuses were tested blindly by polymerase chain reaction in three laboratories using a total of six different primer pairs. RESULTS: Two thymuses tested positive [95% confidence interval (Cl), 0.2-7]. Results from the three laboratories were consistent in all 100 cases. The two fetuses with HIV in the thymus both tested positive in other organs, demonstrating systemic HIV infection. The first fetus, whose mother had advanced AIDS, had died in utero and had diffuse toxoplasmosis. The second died following extremely premature delivery in a pregnancy complicated by repeated bleeding. HIV infection was observed in none of the 92 fetuses that resulted from elective mid-trimester terminations (95% Cl, 0-4). CONCLUSION: The frequency of early in utero HIV infection appears to be low, compared with transmission rates in infants born to HIV-1-infected mothers, suggesting that transmission occurs mostly later in pregnancy and/or at delivery. Specific risk factors may have implications in the occurrence of early as opposed to late transmission. PMID- 7794542 TI - Validating population surveys for the measurement of HIV/STD prevention indicators. AB - OBJECTIVE: To validate the World Health Organization/Global Programme on AIDS (GPA) protocol for measuring HIV/sexually transmitted disease prevention indicators pertaining to knowledge and sexual practices of the general population. METHODS: Data were collected in Uganda during 1993. Three different interview strategies were complemented with qualitative methods, including observations at visits and key-informant interviews. Two interview strategies consisted of structured questionnaires which were applied to 460 randomly selected people aged 15-49 years and 60 intentionally selected women who were known prostitutes. The third strategy involved in-depth interviewing and was applied to a random subset of all respondents (n = 75). RESULTS: The three interview strategies generated similar results for demographic characteristics. The strategies using structured questionnaires gave similar results with regards to the number of reported sex partners and the prevalence of condom use, but differed from in-depth interviews on these aspects. The high numbers of casual sex partners of female prostitutes was confirmed by in-depth interviews but not via the questionnaires. CONCLUSION: The GPA questionnaire may not be optimal to capture people at high risk and to assess sexual behaviour, especially of people at high risk. Nevertheless, the questionnaire provides the most realistic option, since in-depth interviews are expensive and not as objective in assessing trends over time. Evaluation studies of HIV interventions in the general population should therefore be complemented with small qualitative studies to detect and iron out biases in interpreting results. PMID- 7794543 TI - Sociodemographic predictors and temporal trends of extrapulmonary tuberculosis as an AIDS-defining disease in Spain. AB - OBJECTIVE: To identify the factors associated with the presentation of extrapulmonary tuberculosis (EPTB) in AIDS diagnosis and to analyse its temporal trend. DESIGN: Analysis of AIDS surveillance data. METHODS: The study was based on AIDS cases diagnosed in Spain between 1988 and 1993, and reported up to September 1994. The proportion of patients presenting with EPTB at AIDS diagnosis was analysed by sociodemographic characteristics and year of diagnosis. RESULTS: Of the 22,445 AIDS cases diagnosed in Spain from 1988 to 1993, 6526 patients (29.1%; 95% confidence interval, 28.5-29.7) presented with EPTB at diagnosis, making it the most frequent AIDS-defining disease. The highest proportions of EPTB reported at AIDS diagnosis were observed for injecting drug users (IDU; 35.4%) and the heterosexual transmission category (23.5%). The proportion of EPTB was lower in women [relative risk (RR), 0.85; P < 0.001], and higher in 15-29 year-olds (34.2%) and patients with a prison record (44.3 versus 25.4%; RR, 1.75; P < 0.001). AIDS patients resident in provinces with high respiratory TB mortality rates among the general population exhibited a higher proportion of EPTB (RR, 1.45; P < 0.001). The effect of any one variable was maintained by controlling for all others. The proportion of patients with EPTB at AIDS diagnosis revealed a downward trend from 1988 to 1993 (P = 0.007), which was observed in IDU and heterosexuals but not in homosexual/bisexual men (P = 0.421). CONCLUSIONS: Factors such as injecting drug use, prison record or residence in high TB-endemic areas are associated with a greater frequency of EPTB at AIDS diagnosis. These factors must be considered for specific prophylaxis to be efficiently applied. PMID- 7794544 TI - HIV-1 prevalence and risk factors among sexually transmitted disease clinic attenders in Trinidad. AB - OBJECTIVES: To study trends in prevalence and to ascertain risk factors for HIV-1 among sexually transmitted disease (STD) clinic attenders in Trinidad. DESIGN AND METHODS: Serial cross-sectional studies were conducted in 1987-1988 and 1990-1991 at a centralized STD clinic in Port of Spain. A case-control study was carried out to examine in greater detail the demographic and behavioral risk factors for HIV-1 among self-declared heterosexuals in this population. RESULTS: HIV-1 prevalence increased from 3.0% [95% confidence interval (CI), 2.3-3.9] in 1987 1988 to 13.6% (95% CI, 11.8-15.6) in 1990-1991. Age > or = 40 years [odds ratio (OR), 2.0; 95% CI, 1.4-2.8], urban residence (OR, 2.2; 95% CI, 1.6-3.0), and human T-lymphotropic virus-I seropositivity (OR, 3.1; 95% CI, 1.6-6.0) were significant risk factors for HIV-1 in 1990-1991. In the case-control analysis, significant independent risk factors for men included current genital ulcer disease (OR, 5.2; 95% CI, 2.2-12.5), current genital warts (OR, 3.9; 95% CI, 1.2 12.0), having ever had syphilis (OR, 3.2; 95% CI 1.6-6.1), and use of crack cocaine in the preceding 6 months (OR, 6.2; 95% CI, 2.7-14.2). Corresponding risk factors for women were commercial sex work (OR, 5.7; 95% CI, 1.3-25.7), initiation of sexual activity before age 14 years (OR, 4.8; 95% CI, 1.5-16.0), and past non-gonococcal cervicitis (OR, 4.1; 95% CI, 1.3-13.1). CONCLUSIONS: HIV 1 in this setting is primarily heterosexually transmitted in a milieu of unprotected sexual activity fuelled by a crack cocaine epidemic. Targeted interventions to prevent, detect and treat STD and crack cocaine addiction, as well as disrupt their adverse synergism, may substantially reduce HIV-1 transmission in this population. PMID- 7794545 TI - Myeloradiculitis due to Cryptococcus curvatus in AIDS. PMID- 7794547 TI - Is AIDS-related cryptococcosis more frequent among men? PMID- 7794546 TI - Contribution of breastfeeding to the reported variation in rates of mother-to child HIV transmission. PMID- 7794548 TI - Low prevalence of HIV-1 proviral DNA in peripheral blood monocytes and dendritic cells from HIV-1-infected individuals. PMID- 7794549 TI - HIV-1 V3 envelope sequences required for macrophage infection. PMID- 7794550 TI - Willingness of dentists to treat an HIV-infected patient. PMID- 7794552 TI - Does zidovudine cause non-Hodgkin's lymphoma? PMID- 7794551 TI - Cerebral astrocytoma in HIV-infected patients. PMID- 7794553 TI - Serum levels of interleukin-12 in adult and paediatric patients with HIV-1 infection. PMID- 7794555 TI - Statistics from the World Health Organization. PMID- 7794554 TI - Trimethoprim-sulphamethoxazole rechallenge in 20 previously allergic HIV-infected patients after homeopathic. PMID- 7794556 TI - Predictive testing for Huntington's disease: risk perception, reasons for testing and psychological profile of test applicants. AB - In the Center for Human Genetics in Leuven, predictive DNA-testing for Huntington's disease is available as a clinical service since November 1987, initially by DNA-linkage and since mid 1993 by direct mutation analysis. The multidisciplinary approach as well as the detailed test protocol are described. The present paper gives a sociodemographic description of the test applicants, their subjective evaluation of the risk and their motives for requesting the predictive test. Major attention is paid to the personality profile of the applicants who proceeded with testing. Psychometric testing revealed that this group of test applicants did not differ significantly from the general population for most characteristics and even had a number of more positive characteristics e.g. a higher ego-strength. The latter may reflect a self-selection of a more resourceful and emotionally healthier subgroup of at-risk persons. Nevertheless psychological evaluation also has identified a number of applicants with extremely high anxiety levels and other problems, who needed extra pretest and posttest counseling. The relatively high number of withdrawals from the test programme is another indication of the importance of adequate pretest counseling. PMID- 7794557 TI - Fetal akinesia sequence caused by glycogenosis type VII. AB - We report on the autopsy study of a premature boy with multiple joint contractures who died soon after birth of severe lung hypoplasia. Muscle histology showed PAS-positive vacuoles, and electronmicroscopy revealed massive subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical analysis of fresh-frozen muscle tissue disclosed increased glycogen content and a complete lack of phosphofructokinase (PFK) activity. The brain showed focal cerebral and diffuse cerebellar white matter gliosis, and patchy loss of internal granular and Purkinje cells in the cerebellar cortex. The spinal cord was normal. This report describes the first case of PFK deficiency, presenting as a lethal fetal akinesia sequence. PMID- 7794558 TI - X-linked mental retardation and neurological symptoms: a nosological approach. AB - Various clinical classifications of XLMR have been reported. In a recent review on X-linked mental retardation (XLMR) genes, 127 conditions featuring XLMR as a primary or major manifestation were listed (32). In our clinical departments, we have a special interest in families of male patients with mental retardation and neurological symptoms. Since the combination of XLMR and neurological manifestations could be found in almost all categories of the previously reported classifications, we outlined a nosological approach meant for those cases where other specific symptoms are lacking. PMID- 7794559 TI - The Pallister-Killian syndrome in an African individual. AB - We report for the first time an individual of Zulu origin with the Pallister Killian syndrome. Apart from the commonly reported clinical signs, he also had frenula in all four quadrants of the mouth. A broad, short hallux was present. An unusually high level of mosaicism for the isochromosome 12p was found in the lymphocytes. PMID- 7794561 TI - Lysosomal storage diseases in Greece. AB - Over the last 13 years 2745 patients from all over Greece suspected to have a lysosomal storage disorder were referred to the Institute of Child Health. 1581 of those were suspected of having a mucopolysaccharidosis (MPS). 94 cases (3.42% of the total referrals) were positive: 36 patients with MPS, 6 with mucolipidosis (1 type I, 1 type II and 4 type III) and 3 with mannosidosis. Sanfilippo B was not only the most frequent type III MPS but also the most frequent MPS identified in our study. Sphingolipidoses and other lysosomal disorders were diagnosed in 47 cases and non-lysosomal disorders in 19 cases. In our experience Gaucher disease, Sanfilippo B and Hunter syndrome are the most frequent lysosomal disorders in Greece accounting for 23.4%, 17.0% and 7.6% respectively of all diagnosed cases. 13% of the patients originated from Thessaly including 5/16 Sanfilippo B, 2/3 Morquio B, 2/3 Maroteaux-Lamy, 2/6 Metachromatic leukodystrophy and 2/12 Gaucher type 1. PMID- 7794560 TI - Seckel syndrome in a family with three affected children and hematological manifestations associated with chromosome instability. AB - In the present communication we report on a family with three children affected by Seckel-syndrome with mental deficiency, microcephaly, micrognathia and severe growth deficiency. All patients had chromosome instability, which was employed for the prenatal diagnosis of a fourth fetus suspected as a potential Seckel syndrome patient, and one of them had additional hematological disorders. As this condition has been previously characterized as a Seckel syndrome subgroup we report our data concerning this distinct entity. PMID- 7794562 TI - Cytogenetics of the tissue involved in neural tube defects. AB - Cytogenetic techniques were used to study the tissue involved in neural tube defects. Eighteen patients have been evaluated and no specific alterations have been detected. We conclude that, whatever are the mechanisms that lead to neural tube defect, their origins must be searched for at the molecular level. PMID- 7794563 TI - Interstitial deletion of the short arm of chromosome 8: report of a patient and review of the literature. AB - We report a mentally retarded girl with minimal dysmorphic signs. Cytogenetic examination showed an interstitial deletion of chromosome 8: 46, XX, del(8)(p21.2p22). This deletion has not been reported before. We compare the patient with the literature data. PMID- 7794564 TI - Characteristic facial dysmorphism, arachnodactyly and mental retardation: another case. PMID- 7794565 TI - A lethal, unclassifiable form of micromelic dwarfism with posterior cleft palate, multiple cervicothoracal vertebral anomalies and iliac hypoplasia. PMID- 7794566 TI - Hydrocephalus with features of VATER. PMID- 7794567 TI - Conformationally defined cyclohexyl carnitine analogs. AB - Three diastereoisomers of racemic (3-carboxy-2-hydroxy-1 cyclohexyl)trimethylammonium chloride [C10H20NO3+.Cl-; (1S,2S,3S) (2), (1R,2S,3S) (3) and (1S,2R,3S) (4)] were designed as rigid analogs for different low-energy conformational states of carnitine [(1), (3-carboxy-2-hydroxy-1 propyl)trimethylammonium chloride]. Structures (2)-(4) all assume a chair conformation in the solid state, in which the bulky trimethylammonio group occupies the equatorial position. As such, the orientations about C2-C3 in (2), (3) and (4) are all essentially the same as that found for (1) in the solid state (torsion angles for C1-C2-C3-N1 near 180 degrees), while the orientations about C1-C2 in (2)-(4) are such that each diastereoisomer contains a different one of the three possible low-energy staggered conformations predicted for (1) in solution. Comparisons between (1) and (2)-(4) in the solid state revealed that diastereoisomers (2), (3) and (4) provide rigid models for the major low-energy conformations of carnitine. PMID- 7794568 TI - Two related potent antiviral compounds: 3-bromo-N-butyl-4-butylamino-1,8 naphthalenedicarboximide (1) and 4-amino-3-bromo-N-butyl-1,8 naphthalenedicarboximide (2). AB - The crystal structures of two brominated derivatives of 4-amino-N-butyl-1,8 naphthalenedicarboximide [alternative systematic names: 8-bromo-2-butyl-7 butylamino-1H-benzo[de]isoquinoline-1,3(2H)-dione, C20H23BrN2O2, and 7-amino-8 bromo-2-butyl-1H-benzo[de]isoquinoline-1,3(2H)-dione, C16H15BrN2O2] are reported. The N-butyl groups, which are common to both compounds, are perpendicular to the plane of the naphthalenedicarboximide ring system. The butylamino group at position 4 in (1) is in the plane of the naphthalenedicarboximide ring, with the butyl group oriented towards the peri position of the naphthalenedicarboximide ring. This arrangement results in an opening of the (ring C)-N-(butyl C) angle. PMID- 7794569 TI - (Z)-5-(2-thienylmethylene)-2,4-imidazolidinedione. AB - The major product formed in the thermolysis of 5-diazouracil in thiophene at 423 433 K has been identified as the unexpected compound (Z)-5-(2-thienylmethylene) 2,4-imidazolidinedione, C8H6N2O2S, by X-ray analysis. The molecule is a hydantoin derivative with a thienylmethylene group substituted at the 5-position. The structure is disordered in that the thiophene ring exists in two orientations which are related by an approximate 180 degree rotation about the C(6)-C(7) bond. All of the N and O atoms are involved in an intermolecular hydrogen-bonding network via N-H...O interactions. This network consists of an infinite chain along the a-axis direction and a cyclic trimer arrangement which branches from this chain. The molecules are arranged in the unit cell in pleated sheets which are approximately perpendicular to the c axis. PMID- 7794570 TI - Magnetic resonance imaging compared to echocardiography to assess left ventricular mass in the hypertensive patient. AB - Echocardiography (ECHO) is useful to document changes in left ventricular mass (LVM) in groups of patients, but may be too variable for use in the individual patient. Magnetic resonance imaging (MRI) may be a more precise and reliable method to quantify the mass of the left ventricule. This study reports the accuracy, precision, and reliability of LVM estimates by MRI as compared to data obtained by ECHO in hypertensive patients. Accuracy referred to the comparison of LVM by MRI to anatomical LVM determined by autopsy. Precision was examined using 34 duplicate MRI images and by blindly reading 24 duplicate M-mode strips. Reliability was assessed by MRI in four subjects over 2 months, and by ECHO in 22 hypertensive patients over 2 weeks. Agreement between MRI and ECHO estimates of LVM was determined in the same 17 hypertensive patients using linear regression. MRI LVM estimates were within 17.5 g (95% CI) of the true LVM. The linear agreement between MRI and ECHO estimates of LVM could be described by the equation MRI = 0.61 x ECHO + 49.57 (r = 0.63, P < .01). The precision of LVM by MRI (11 g) was over twice that observed with ECHO (26 g). The reliability of MRI LVM estimates was more consistent (+/- 8 g) than that for ECHO (+/- 49 g). MRI appears to be a more precise and reliable method for measuring LVM, and would be more suitable than ECHO for the clinical evaluation of the individual patient. PMID- 7794571 TI - Progressive improvement in the structure of resistance arteries of hypertensive patients after 2 years of treatment with an angiotensin I-converting enzyme inhibitor. Comparison with effects of a beta-blocker. AB - To investigate the effects of antihypertensive drugs on resistance artery structure, 17 essential hypertensive patients were randomly assigned to be treated with an angiotensin I-converting enzyme inhibitor, cilazapril, or a beta blocker, atenolol, for 2 years. Blood pressure was well controlled throughout the 2 years. Before starting treatment, at the end of the first year and at the end of the second year, patients were subjected to gluteal subcutaneous fat biopsies, from which resistance-size arteries were dissected to be studied. The media width to lumen diameter ratio of arteries from patients in the cilazapril group was 7.5 +/- 0.3% before starting treatment, and decreased significantly (P < .05) to 6.3 +/- 0.2% at the end of the first year, and to 5.8 +/- 0.2% at the end of the second year, at which time it was not different from that of arteries from normotensive subjects (5.2 +/- 0.2%). In patients treated with atenolol, resistance arteries exhibited a media-to-lumen ratio of 8.0 +/- 0.6% before treatment, 8.1 +/- 0.5% after 1 year of treatment, and 7.9 +/- 0.3% at the end of the second year of treatment, all significantly higher (P < .01) than that of arteries from normotensive subjects. Thus, treatment for 2 years with the angiotensin I-converting enzyme inhibitor cilazapril resulted in progressive normalization of the structure (media-to-lumen ratio) of gluteal subcutaneous fat resistance arteries of essential hypertensive patients, whereas there was no change in patients treated with the beta-blocker atenolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794572 TI - Comparison of intrabrachial and finger blood pressure in healthy elderly volunteers. AB - This study was performed to compare continuous Finapres (FIN) and intrabrachial (IAP) blood pressure in healthy elderly volunteers. Fifteen elderly subjects (age 71 to 83) without cardiovascular disease and an intraarterial mean (range) systolic and diastolic blood pressure of 162 (122 to 195) and 73 (62 to 88) mm Hg, respectively, participated in the study. A 10-min head-up tilt, 10 min active standing, a 15-sec Valsalva, and a 5-min mental arithmetic were performed in random order. Beat-to-beat values of systolic, diastolic, and mean arterial pressure were analyzed. At rest, FIN underestimated IAP by 16.8 +/- 2.6 (SE), 10.8 +/- 1.5, and 17.5 +/- 1.6 mm Hg for systolic, diastolic, and mean arterial blood pressure, respectively (P < .05). During head-up tilt, FIN overestimated the intraarterial systolic blood pressure response by 7.2 +/- 1.6 (SE) mm Hg (P < .05). Group-averaged changes in diastolic and mean arterial IAP were followed closely by FIN. During standing, Finapres closely followed intraarterial diastolic and mean arterial pressure but the increase in systolic blood pressure was higher at the finger as compared to intrabrachial recordings, resembling the results of head-up tilt. During the Valsalva maneuver, maximal responses in systolic, diastolic, and mean arterial pressure were underestimated by FIN by 12.1 +/- 3.3 (SE), 6.8 +/- 2.7, and 7.1 +/- 1.7 mm Hg, respectively (P < .05 for all parameters). During mental arithmetic, FIN underestimated the intraarterial systolic blood pressure response by 6.1 +/- 2.7 (SE) mm Hg (P < .05), while diastolic and mean arterial pressure responses were followed correctly by FIN. It is concluded that apart from systolic blood pressure, FIN closely follows intraarterial blood pressure responses for the orthostatic maneuvers and mental arithmetic. During Valsalva, the rapid changes in blood pressure were followed in direction but not in magnitude. PMID- 7794573 TI - Ambulatory blood pressure in mild hypertensive women taking oral contraceptives. A case-control study. AB - The aim of the present study was to compare the ambulatory blood pressure levels in mild (stage 1) hypertensive women using oral contraceptives and respective values in nonusers of oral contraceptives with similar office blood pressure. The study group consisted of 24 mild hypertensive patients taking low dosage estrogen progestogen oral contraceptives. Seventy women of similar age and body mass index who had never used oral contraceptives served as a control group. Both daytime and nighttime systolic blood pressure values were significantly higher in oral contraceptive users. There was an average 8.3 mm Hg difference (95% confidence interval, 3.0 to 13.7 mm Hg; P = .003) for the daytime and 6.1 mm Hg difference (95% confidence interval, 0.4 to 11.8 mm Hg; P = .04) for the nighttime. No significant differences in ambulatory diastolic blood pressure between the two groups were found. These data provide evidence that hypertensive oral contraceptive users with the same office blood pressure as that in hypertensive noncontraceptive users have a significantly higher ambulatory systolic blood pressure. Our results support the opinion that alternative methods of contraception should be considered for hypertensive women in place of oral contraceptives. PMID- 7794574 TI - Metoprolol minimizes nighttime blood pressure dip in hypertensive black males. AB - Twelve hypertensive black males completed the study, which was conducted to evaluate the effect of metoprolol on 24-h ambulatory blood pressure (ABP). Study participants took 50 mg to 100 mg metoprolol twice daily for a minimum of 3 weeks. Metoprolol had no significant effect on blood pressure (147/90 +/- 11/8 mm Hg v 151/88 +/- 16/8 mm Hg, baseline v treated, respectively) in spite of causing significant reductions in heart rate (87 +/- 9 beats/min v 69 +/- 7 beats/min, P < .001). Only one subject had a > or = 10 mm Hg decrease in 24-h diastolic blood pressure. The nighttime fall in blood pressure was minimized by metoprolol and clinically significant increases in daytime or nighttime blood pressure were noted in 58% of patients. Metoprolol therapy failed to lower blood pressure and eliminated the normal nighttime decline in blood pressure. Since the nighttime decline in blood pressure is thought to protect against target organ damage, it may be important to identify antihypertensive agents which preserve or enhance the nighttime blood pressure dip. PMID- 7794575 TI - Stimulation of aldosterone by ACTH in normal and hypertensive pregnancy. AB - The observation that plasma renin (PRC) is suppressed to a greater degree than aldosterone (Paldo) concentration in preeclampsia has led us to examine the role of nonangiotensin factors in the control of aldosterone release in pregnancy. The aim of this study was to determine whether the aldosterone response to adrenocorticotrophic hormone (ACTH) was altered in normal or preeclamptic pregnancy. After 4 days of a 100 mmol/day sodium diet, serum cortisol, PRC, and Paldo were measured every 20 min during an incremental low-dose ACTH infusion (over 80 min) in 10 nonpregnant, nine normal pregnant, and nine preeclamptic women. Baseline PRC, Paldo, and cortisol were significantly higher in normal pregnant than in nonpregnant women (P < .05), but serum ACTH concentration was similar. Following ACTH infusion there was significant stimulation of cortisol in both groups (P < .001) and the maximum rise (963[824,1163] nmol/L, median [interquartile range]) was greater in pregnant than in nonpregnant women (507[402,837]), P < .01. Plasma aldosterone also rose significantly following ACTH in both groups (P < .01) and the maximum rise was also greater in normal pregnant (1186[828,2609] fmol/mL) than nonpregnant women (874[598,1065]), P = .05. These changes were not related to basal cortisol or aldosterone concentrations in either group. Baseline PRC was significantly lower in preeclamptic than in normal pregnant women (P < .05) but Paldo, serum ACTH, and cortisol concentrations did not differ significantly. Following ACTH there was significant stimulation of cortisol in both groups (P < .0001) and the maximum increment in preeclamptic women following ACTH infusion (807[708,1007] nmol/L) was similar to that of normal pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794576 TI - Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men. AB - The present study was undertaken to examine the relationships between insulin sensitivity, blood pressure (BP), and cardiovascular reactivity, and to assess sympathetic nervous system influence. Insulin sensitivity (GDR/I; euglycemic glucose clamp technique) was related to BP and heart rate (HR) in different situations in 40 healthy young men: in the laboratory, during a mental arithmetic stress test, and during baseline conditions at home. GDR/I correlated with supine diastolic BP in the laboratory and with maximum diastolic BP during mental stress (r = -0.46, P = .003; r = -0.62, P = .0001, respectively), but not so strongly with diastolic BP measured at home (r = -0.29, P = .09). Diastolic BP during stress and body mass index were the only independent explanatory variables of GDR/I in multiple regression analysis (multiple R = 0.71, R2 = 0.50, P < .0001). GDR/I and systolic BP were not significantly correlated at any time. GDR/I correlated negatively with HR in the laboratory and with maximum HR during mental stress, but not with HR at home. Maximum plasma epinephrine during stress correlated with stress BP and HR (r = 0.53, P = .001; r = 0.70, P < .0001, respectively) and negatively with GDR/I (r = -0.36, P < .05). In the present study, GDR/I is related to diastolic but not to systolic BP, and more closely correlated to diastolic BP and HR measured during mental stress than to diastolic BP and HR during baseline conditions at home.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794577 TI - The effect of enalapril with and without hydrochlorothiazide on insulin sensitivity and other metabolic abnormalities of hypertensive patients with NIDDM. AB - The effect of 20 mg of enalapril with and without 12.5 mg of hydrochlorothiazide on glucose metabolism insulin sensitivity and lipids was evaluated in hypertensive non-insulin-dependent diabetes. Ten mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus were treated for 8 weeks with 20 mg enalapril once a day, and then divided into two groups of 5 patients each for a second 8 weeks of treatment with enalapril alone or in combination with hydrochlorothiazide, 12.5 mg once a day. Blood pressure, fasting plasma glucose, lipids and insulin, glycosylated hemoglobin, and insulin sensitivity were measured at baseline and after 8 and 16 weeks. Results were analyzed by the ANOVA test for repeated measures and all values are given as mean +/- SD. Diastolic blood pressure decreased significantly after the first and second period of enalapril and after the combination of enalapril and hydrochlorothiazide. Glycosylated hemoglobin dropped significantly after the first and second period of enalapril monotherapy. Plasma triglycerides and fasting plasma insulin decreased significantly after the 16 weeks of enalapril. Insulin-mediated glucose uptake increased significantly after 8 and 16 weeks of monotherapy with enalapril. No significant difference was observed in any of the metabolic characteristics, including insulin sensitivity, between the values after 8 weeks of enalapril alone and the final values of the enalapril-treated and the enalapril/hydrochlorothiazide-treated groups. It is concluded that enalapril improves some of the metabolic parameters, including insulin sensitivity, of hypertensive diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794578 TI - Clinical efficacy of force titrated doses of diltiazem extended-release. A placebo controlled study. AB - Thirty patients with clinical and ambulatory essential hypertension were treated in a double-blind fashion with force titrated doses of placebo or diltiazem once daily (OD) extended-release (ER) 120, 240, 360, and 540 mg to characterize the full-dose range of the new formulation. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters. Doses of > or = 240 mg significantly decreased clinic diastolic blood pressure, whereas systolic blood pressure was significantly lowered by the 540-mg dose. Moreover, compared with placebo, ambulatory blood pressure was significantly decreased by the 360- and 540-mg dose levels. Trough/peak ratios for systolic and diastolic blood pressures were 50% and higher at dose levels of 240 mg and above. Adverse reactions with diltiazem OD ER were generally mild and similar to those observed with placebo. The findings of this study indicate that the most favorable effects of diltiazem OD ER were observed in response to the 360- and 540-mg dose levels. The dose escalation forced titration study design appears to be a valuable tool in obtaining rigorous dose-response data of new antihypertensive agents. PMID- 7794580 TI - In situ hybridization shows increased endothelin-1 mRNA levels in endothelial cells of blood vessels of deoxycorticosterone acetate-salt hypertensive rats. AB - Endothelin-1 is a potent vasoconstrictor peptide produced in blood vessels and other tissues that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. Our previous studies have documented increases in endothelin-1 peptide content and gene expression in mesenteric arteries and thoracic aorta of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Although changes in endothelin-1 were observed in the blood vessels of hypertensive rats, the exact cellular sites of these changes were not identified clearly. In the present study we investigated endothelin-1 gene expression in DOCA-salt hypertensive rats by in situ hybridization histochemistry using a high specific activity 35S-labeled complementary RNA probe. Robust increases in endothelin-1 mRNA levels were observed in both mesenteric blood vessels and aorta of DOCA-salt hypertensive rats as compared with the vessels from the uninephrectomized control rats. In both cases it was shown clearly that these increased endothelin-1 mRNA levels only originated in the endothelial cell layer, not in the underlying smooth muscle cells. Higher expression levels of endothelin-1 mRNA by the endothelial cells of DOCA-salt hypertensive rats may play an important role in vascular hypertrophy and in the maintenance of elevated blood pressure in this and perhaps other models of experimental hypertension. PMID- 7794581 TI - Lack of placebo effect on ambulatory blood pressure. AB - Several studies have reported that, at variance with clinic blood pressure, ambulatory blood pressure is not reduced by treatment with placebo. However, this evidence has usually been obtained in small groups of subjects and no data are available from a larger sample of patients. To address this issue we have analyzed data from 116 outpatients involved in placebo-controlled studies on antihypertensive treatment. The patients were studied before and at the end of a 6- to 8-week period of placebo. In all patients, blood pressure was measured by sphygmomanometry and over the 24 h by automatic ambulatory monitoring. Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressure (-5.3 +/- 1.1 and -4.4 +/- 0.6 mm Hg, respectively; P < .01), but not in 24-h, daytime and nighttime blood pressure. Hourly systolic and diastolic blood pressure profiles were virtually superimposable in the two different periods, except for the first 4 h, in which systolic blood pressure was slightly but significantly lower during than before placebo (149.5 +/- 1.2 v 146.4 +/- 1.2 mm Hg; P < .05). These results provide a large database indicating that 24-h average blood pressure is not reduced by placebo, thus it is not necessary to include a placebo control group in antihypertensive drug studies in which ambulatory blood pressure monitoring is employed. A small placebo effect occurs, however, in the first hours of ambulatory monitoring. This may lead to a slight overestimation of the peak blood pressure effect of a drug and an underestimation of its trough-to-peak ratio if placebo correction of the data is not made or if the first part of ambulatory blood pressure monitoring is not excluded from data analysis. PMID- 7794579 TI - Alteration of prejunctional alpha 2-adrenergic autoinhibition in DOCA-salt hypertension. AB - The possible involvement of prejunctional alpha 2-adrenergic autoinhibition in hypertension is still controversial. The aim of this study was to determine the functional integrity of this regulatory mechanism in conscious DOCA-salt hypertensive rats, a model characterized by an increased sympathetic tone and reactivity. Basal and hemorrhage-induced increases in catecholamine and immunoreactive neuropeptide Y (NPY) levels were compared between control and yohimbine (alpha 2-adrenergic receptor antagonist) pretreated normotensive and DOCA-salt hypertensive rats. DOCA-salt hypertensive rats had higher basal norepinephrine levels (NE), as well as increased NE and epinephrine (EPI) responses to a 15-mL/kg hemorrhage as compared to control normotensive rats. In normotensive animals, yohimbine (0.5 mg/kg, intravenous [iv]) doubled plasma NE, EPI, and NPY levels in basal conditions and in response to the hemorrhage. In contrast, the same treatment had smaller or no effect on basal NE levels and on the hemorrhage-induced responses in DOCA-salt hypertensive rats, although basal EPI levels were increased in this group. These results therefore suggest a decreased function of the prejunctional alpha 2-adrenergic autoinhibitory mechanism at the level of sympathetic nerve terminals and adrenal medulla during sympathetic hyperactivity in DOCA-salt hypertension. This dysfunction could in part explain the hyperactivity and hyperreactivity of the sympathetic nervous system observed in this model, and thus contribute to the elevation of blood pressure in DOCA-salt hypertension. PMID- 7794582 TI - Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. AB - The association of hypertension with insulin resistance has been reported. Troglitazone (CS-045) is a newly developed antidiabetic agent that enhances insulin sensitivity. Its antidiabetic effects have been confirmed in diabetic animals and patients. The present study was performed to evaluate whether the amelioration of hyperinsulinemia by troglitazone lowers blood pressure in essential hypertensives. Troglitazone was administered orally to 18 outpatients with essential hypertension complicated by mild diabetes at a dose of 200 mg twice a day for 8 weeks. Blood pressure was decreased from 164 +/- 3/94 +/- 2 mm Hg to 146 +/- 3 (P < .001)/82 +/- 3 (P < .05) mm Hg at 8 weeks of the treatment period. Pulse rate did not change. Fasting plasma glucose changed from 159 +/- 10 mg/dL to 144 +/- 14 mg/dL at 8 weeks (P < .05). Plasma insulin (IRI) levels changes from 9.1 +/- 1.2 microU/mL to 6.3 +/- 0.8 microU/mL at the endpoint of treatment (P < .1). Decrease in mean blood pressure from the control period to the endpoint of the treatment correlated significantly with decrease in IRI (r = 0.59, P < .05). In summary, troglitazone treatment induces improvement in both glucose metabolism and blood pressure control in essential hypertensive patients with diabetes mellitus. These results suggest that insulin resistance or plasma insulin level plays a role in the pathogenesis of essential hypertension. PMID- 7794583 TI - Maternal environment defines blood pressure and its response to troleandomycin in spontaneously hypertensive rats. AB - Relationship between family-3A cytochrome P-450-dependent (troleandomycin inhibitable) and maternal environmental-dependent systolic blood pressure (SBP) was investigated in spontaneously hypertensive rats (SHR). Adult SHR nursed by foster or natural SHR mothers had indistinguishable SBP. Troleandomycin reduced 50% of Wistar-Kyoto (WKY)-SHR strain difference in SBP. SHR having WKY foster mothers had SBP similar to troleandomycin-reduced SHR levels, which was unaffected by troleandomycin. The two components of SBP elevation appear identical. Because observations of others demonstrated that WKY fostered to SHR show no SBP increase, the maternally dependent/troleandomycin-sensitive component of SBP elevation may reflect epistatic interaction between genes determining maternal differences and offspring sensitivity, respectively. PMID- 7794584 TI - Calcium channel blockers. Is it time to split the lump? AB - Antihypertensive drug classes such as thiazide diuretics, angiotensin-converting enzyme inhibitors, beta-adrenergic blocking agents, peripheral alpha 1 antagonists, and central alpha 2-agonists all describe therapeutic agents that are quite similar to each other and strikingly different from members of the other classes. A glaring exception is the rubric "calcium channel blocker," under which strikingly dissimilar drugs have been lumped. Although the phenylalkylamines (verapamil and gallapamil) and benzothiazepines (diltiazem and TA3090) bind at different receptors on the alpha 1 component of the calcium channel, they are reasonably similar in their clinical pharmacology. For example, both types of drugs slow the heart rate and there are intravenous preparations that are used to treat supraventricular tachycardia. The dihydropyridines (nifedipine and many others) bind to another receptor on the alpha 1 component, but have markedly different pharmacologic properties. For example, they tend to increase the heart rate, do not cause constipation, but are more likely to cause peripheral edema. I propose that we refer to this entire class of drugs as "calcium antagonists," that we continue to refer to verapamil, diltiazem, and similar drugs as "calcium channel blockers," but recognize the very different properties of nifedipine and like drugs by referring to them as dihydropyridines or DHPs. PMID- 7794585 TI - Expert comments on the JNC V consensus guidelines. PMID- 7794586 TI - The Report of Fifth Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure: a "loose" constructionist view. PMID- 7794587 TI - High fructose diet and blood pressure. PMID- 7794588 TI - Community mental health care for former hospital in-patients. Predicting costs from needs and diagnoses. AB - BACKGROUND: In the UK the replacement of long-term in-patient care with community based support has been part of central government health policy for many years. One of the challenges of implementing such a policy is the prediction of support and service needs in the community and the associated costs. METHOD: Using research data from north London analyses were undertaken to examine the associations between service use and costs in the community and the characteristics of hospital in-patients. RESULTS: Although clinical diagnosis was not a useful predictor of either service utilisation or costs, more than a third of the variation in community care costs could be explained by symptoms, behaviour and personal characteristics at least one year earlier. PMID- 7794589 TI - The social costs of anxiety disorders. AB - BACKGROUND: The social costs of anxiety disorders, which afflict a substantial proportion of the general population in the United States, are considered. METHOD: Data from the National Institute of Mental Health (NIMH) Epidemiological Catchment Area Program were analysed. RESULTS: Over 6% of men and 13% of women in the sample of 18,571 had suffered from a DSM-III anxiety disorder in the past six months. Nearly 30% of those with panic disorder had used the general medical system for emotional, alcohol or drug-related problems in the six months prior to the interview. Those with anxiety disorders were also more likely to seek help from emergency rooms and from the specialised mental health system. Men with panic disorder, phobias or obsessive-compulsive disorder in the previous six months are more likely to be chronically unemployed and to receive disability or welfare. DISCUSSION: Once correctly diagnosed there are safe and effective psychopharmacologic and behavioural treatments for the anxiety disorders. Nevertheless the burden of anxiety disorders extends beyond the direct costs of treatment to the indirect costs of impaired social functioning. PMID- 7794591 TI - The economic consequences of not treating depression. AB - BACKGROUND: A conceptual framework is described for a broad cost-benefit evaluation of improved financial access to treatment of untreated affective disorders. METHOD: The analysis provides an estimate of the value of resources needed to provide improved access to treatment, and it compares these resources to the value of resources the improved access to treatment might save. RESULTS: The cost-benefit analyses based on recent cost of mental illness studies provide some evidence that appropriately treating people with untreated affective disorders is cost-beneficial. CONCLUSION: Patients, providers and buyers of health care should be further encouraged to pay more attention and to commit more financial resources to the treatment of affective disorders. PMID- 7794590 TI - Costs and offset effect in panic disorders. AB - BACKGROUND: The study is aimed at assessing the costs before and after the diagnosis and the provision of effective treatment for panic disorder (PD), and the offset effect related to the psychiatric encounter. METHOD: A 24-month prepost design was used to collect data on clinical status and health care services utilisation in a natural environment. The 61 PD patients' assessment included the SCID-UP, ratings on general functioning, improvement, severity of symptoms and level of disability. All health care services used and lost workdays were recorded. RESULTS: Both sociodemographic characteristics and the outcome show that this was a standard group of PD patients, who received effective treatment for their condition. The total direct costs of health care use during the previous year and the year after the diagnosis were, respectively, US$ 29,158 and US$ 46,256. The indirect costs of lost productivity were US$ 65,643 in period I and US$ 13,883 in period II. CONCLUSIONS: A strong offset effect (94%) has been found in this study, significantly greater than the one described for psychiatric disorders as a whole. The costs of nondiagnosis are usually overlooked when estimating the global costs of PD. Methods for improving early detection of PD may substantially reduce the costs incurred before diagnosis. PMID- 7794592 TI - The economic burden of affective disorders. AB - BACKGROUND: This paper summarises the methods and sources of data used to estimate costs of affective disorders and presents the results. METHOD: A timing model employing regression analysis was developed to estimate morbidity costs. This model measures the lifetime effect on current income of individuals with affective disorders, taking into account the timing of onset and the duration of these disorders. RESULTS: Affective disorders imposed an estimated US$ 20.8 billion burden in 1985 and US$ 30.4 billion in 1990 in the US. Affective disorders represent 21% of the costs of all mental illnesses. Direct treatment costs comprised 58.4% of the total in 1985; morbidity costs, 8.1%; mortality costs, the present value of future earnings lost due to premature mortality, 28.9%, based on a 6% discount rate; and other related costs, including the cost of crime, lost productivity due to incarceration, and caregiver services, 4.6%. Private sources account for 49% of the total direct expenditures for treatment of persons with affective disorders; state and local funds, 26%; and federal funds, 25%. CONCLUSION: In light of the high burden of affective disorders on societal resources, more attention should be directed at comprehensive, research-based strategies to reduce the prevalence of these disorders in the United States. PMID- 7794593 TI - Cost containment and mental health outcomes: experiences from US studies. AB - BACKGROUND: Cost containment mechanisms, such as prepayment, are being considered or implemented in the US and elsewhere, but there have been few studies of the effects of such mechanisms on quality or outcomes of care for individuals with serious psychiatric disorders. METHOD: Key results from US studies on cost containment and their implications are reviewed. RESULTS: Cost savings in out patient mental health care can be achieved through increasing the share of costs paid by the covered individual or through prepayment, but individuals with the greatest psychological distress or poor people may achieve worse outcomes under greater cost containment. Quality of care may be poorer under some forms of prepayment than under fee-for-service care, yet a national prospective payment mechanism for depressed elderly in-patients was not associated with a marked drop in quality or outcomes of care among those admitted. CONCLUSIONS: Prepayment, relative to fee-for-service is not always associated with lower outcomes or quality of care for affective disorders. Under cost containment, quality and outcomes of care, especially for the sick poor, should be monitored to identify adverse consequences. PMID- 7794594 TI - Costs and benefits of hospital and day treatment with community care of affective and schizophrenic disorders. AB - BACKGROUND: A randomised controlled trial of day treatment with community care for patients with schizophrenic and affective disorders, referred for in-patient psychiatric treatment, was conducted to evaluate patterns of treatment and the course of illness with its psychosocial consequences over a period of two years. METHOD: Seventy patients, of whom 34 had affective and 36 had schizophrenic disorder, were assigned to the experimental condition (day treatment with ambulatory and domiciliary care), and 33 patients, of whom 16 had affective and 17 had schizophrenic disorder, were assigned to the control condition of standard clinical care. RESULTS: Day treatment with community care was feasible for 40.6% of the affective patients and 33.3% of the schizophrenic patients. The direct treatment costs of both disorders, based on numbers of in- and day-patient days and out-patient contacts over two years, appeared more or less the same. Patients benefited equally from day treatment as from in-patient treatment, although there were some gains in self-care and in functioning in the household among experimentals. Although schizophrenics were socioeconomically worse off, and also suffered from more (severe) symptoms and social disabilities than the affective patients at entry into the study, they were similar at two years. This finding is unexpected, compared with other follow-up studies. Extra cost for patients and families were not observed. Patients and their families in the experimental condition were significantly more satisfied with the treatment. Experimental patients spent much more time at home during admission, remained much less time in secluded wards, and were more compliant with treatment. CONCLUSIONS: Day treatment could be considered a cost-effective alternative to in-patient treatment. PMID- 7794595 TI - The economics of depression in primary care. Department of Health initiatives. AB - BACKGROUND: Most mental illness is treated in primary and not secondary care settings, with depression and anxiety the commonest conditions encountered. METHOD: The paper describes on-going Department of Health initiatives to optimise the primary care of common mental illnesses such as depression. DISCUSSION: Primary care attenders with depression are often higher consumers of general health care than non-depressed attenders. Further data will become available soon from these ongoing studies to inform the debate on the optimal use of available resources in primary care. There is a particular need to evaluate non pharmacological interventions in primary care. PMID- 7794596 TI - Economics of anxiety and depression. Introduction. PMID- 7794597 TI - [Modification of the pharmacokinetics of some antibiotics by oral administration with an L-(-)verbenone beta-cyclodextrin complex]. AB - With the aim to evaluate the effect of L (-) Verbenone on the pharmacokinetic of some antibiotics, a compound has been prepared with beta cyclodextrin, allowing the administration per os. Pharmacological studies have been carried out using erythromycin and ampicillin, determining their kinetics in the hepatic and lung tissues after administration to albino mice. The results show that L (-) Verbenone modifies the distribution of the antibiotics used; it increases their concentration at lung level while the concentration at hepatic level remains unchanged. PMID- 7794598 TI - Development of a thin membrane glucose sensor using beta-type crystalline chitin for implantable biosensor. AB - A biocompatible thin membrane glucose sensor has been developed using beta-type crystalline chitin as a supporting material for the purpose of implantable biosensor. Gold electrode was formed by vapor deposition of the surface of glucose oxidase-immobilized beta-chitin membrane. The sensor showed rapid responses to glucose and H2O2 (< 45 s in batch operation), and addition of 2,6 dichlorophenolindophenol as a mediator caused expansion of the measuring range. To investigate the possible uses for the implantable, the sensor sterilization and toxicity were studied. Sterilization with ethylene oxide was achieved by exposing samples, and a decrease in activity was permissible for measurements of body fluid. From the results of the toxicity assay using mouse fibroblast cells, beta-chitin sensor, constructed with chitin, glucose oxidase and gold electrode, showed no particular toxicity. PMID- 7794599 TI - Optimizing antibody production in batch hybridoma cell culture. AB - Optimizing productivity by hybridoma cells relies partly on developing suitable methods for screening and selection of high producing cultures and on understanding regulation of antibody production. In this study, the behavior of hybridoma cells in batch culture was investigated using flow cytometry, and a simple model for antibody production was used to explain production data obtained from these cultures. Surface antibody fluorescence values were found to closely follow the decreasing trend of specific antibody secretion rate over the course of several batch cultures. Therefore, for the hybridoma cell lines studied here (ATCC HB124 and TIB138), surface immunofluorescence levels can be used to select high producing cells as well as to monitor culture productivity. Surface and intracellular antibody fluorescence values were also found to be correlated for cells exhibiting a bimodal distribution with respect to intracellular antibody content. The population of cells containing a bimodal distribution with respect to intracellular antibody content. The population of cells containing lower levels of intracellular antibody was determined to secrete significantly less antibody than the population possessing high intracellular antibody concentrations. Factors which influence antibody production rates and possible strategies for optimizing monoclonal antibody yield are discussed. PMID- 7794600 TI - Transgenic rabbits as bioreactors for the production of human growth hormone. AB - Gene farming is one of the most promising areas in modern biotechnology. To assay the potential usefulness of transgenic rabbits as bioreactors, one call embryos were microinjected with a chimeric gene comprising 5' sequences from mouse whey acidic protein gene (mWAP) linked to the human growth hormone (hGH) gene. Transgenic animals were obtained and the presence of the foreign protein was detected in the milk and serum of these animals at levels of up to 50 micrograms ml-1 and 0.6 ng ml-1, respectively. Founder transgenics were able to transmit the microinjected gene to the first filial generation in a Mendelian fashion. These results showed that transgenic rabbits could constitute a suitable system for the rapid production of recombinant proteins in the milk of lactating females. PMID- 7794601 TI - CT of small-bowel neoplasms. AB - The diagnosis of neoplasms of the small intestine remains a difficult challenge owing to their nonspecific clinical presentation. CT is an efficient and contributive tool in their diagnosis and preoperative staging. Enabled by CT, the evaluation of the intramural and extramural portions of such tumors complements the mucosal analysis allowed by barium examination. Strict technical rules should be applied to minimize pitfalls mainly resulting from insufficient bowel opacification. Although characteristic appearances are rare, typical CT findings may suggest a specific diagnosis where lipomas and carcinoid tumors are concerned. PMID- 7794602 TI - CT for the evaluation of carcinomas in the colon and rectum. AB - The role of conventional CT in assessing patients with colorectal tumors is well established. The low accuracy of CT for identifying early stages of primary colorectal cancers prevents the routine use of CT for preoperative staging. Nevertheless, CT is useful in examining patients suspected of having extensive disease, in deciding whether a patient will benefit from preoperative radiation, in designing radiation ports, and in detecting complications related to the neoplasm. For recurrent colorectal neoplasm, CT has the premier role. CT surpasses colonoscopy in detecting early masslike tumor recurrence at the anastomotic site because of its extrinsic component, and CT and MRI are the only methods that can fully evaluate cases of total abdominoperineal resection. After total abdominoperineal resection, however, CT cannot determine with certainty that a soft tissue density in the surgical bed represents recurrent tumor. In patients with colorectal neoplasms, preliminary results with multiplanar and three-dimensional reconstructions of helical CT images are promising, but their role needs further investigation. PMID- 7794603 TI - Role of CT in evaluating patients with small-bowel obstruction. AB - The accurate and rapid diagnosis of acute small-bowel obstruction has troubled surgeons and radiologists for more than a century. With the advent of CT, solving the problem is now a possibility. CT can accurately diagnose obstruction, determine the likely cause and location, and even suggest whether there is associated bowel ischemia or strangulation. PMID- 7794604 TI - CT in the early detection of strangulation in intestinal obstruction. AB - The role of CT in evaluating the gastrointestinal tract has increased recently because CT demonstrates pathological conditions involving the bowels, mesenteric vessels, and peritoneal cavity well. In patients who have an intestinal obstruction, the observation of both bowel loop configuration and mesenteric vessels on CT is the key to identifying the site and cause of obstruction and determining the absence or presence of intestinal strangulation. Although many clinical and radiological findings reported in the literature are not seen in the early stages of intestinal strangulation, CT might assist in its early detection. This article reviews the clinical, pathophysiological, and radiological aspects of strangulating obstruction with emphasis on the role of CT in its early diagnosis. PMID- 7794606 TI - CT of the colon in frail elderly patients. AB - CT is presented as an alternative to barium enema examination for the investigation of the colon in frail elderly patients. Carcinomas can be detected reliably and the investigation is better accepted by patients and staff alike. Furthermore, extracolonic lesions are shown. Obviously small polyps are missed, but such lesions are less relevant in older patients. The CT technique is described, and some of the initial difficulties encountered during the adoption of this policy are discussed. PMID- 7794605 TI - Role of CT in the acute nontraumatic abdomen. AB - The diagnostic workup of the acute abdomen always begins with a precise clinical history, a complete physical examination, and careful reading of plain films. Commonly performed additional imaging studies include contrast examination and, more recently, ultrasound. CT offers the advantage of allowing a comprehensive diagnostic evaluation of both solid and hollow viscera in neoplastic as well as in inflammatory and vascular disorders. PMID- 7794607 TI - CT of blunt trauma to the bowel and mesentery. AB - Injuries to the bowel and mesentery are found in approximately 5% of all patients undergoing laparotomy after blunt abdominal trauma. Bowel and mesenteric injuries are often subtle and difficult to diagnose, and a delay in the diagnosis is associated with increased mortality and morbidity. CT is the best imaging method for diagnosing injuries to the bowel and mesentery. With meticulous scanning techniques, most significant bowel and mesenteric injuries can be reliably identified with CT preoperatively, and associated injuries to other abdominal viscera can be confirmed. PMID- 7794608 TI - CT of inflammatory disease of the colon. AB - CT plays an important role in the evaluation of patients with suspected colonic inflammation. High-resolution, thin-section imaging of the gastrointestinal tract allows assessment of both the intraluminal and extraluminal components of colonic disease, thereby enabling radiologists to detect and stage colonic pathology accurately. In addition, CT can be used to guide percutaneous drainage of abscess collections, often obviating the need for surgical intervention. This article describes CT techniques for diagnosing inflammatory diseases of the colon as well as the typical CT appearances. PMID- 7794609 TI - Rehospitalization and growth of infants with bronchopulmonary dysplasia: a matched control study. AB - OBJECTIVE: To determine the risk of hospitalization and the growth during the first year of life in infants with bronchopulmonary dysplasia (BPD) and birthweight matched controls. METHODOLOGY: The study population consists of 78 infants of 26 to 33 weeks gestation with BPD of whom 20 were discharged on home oxygen therapy. The 78 control infants were matched with the study infants for broad based birthweight categories. Infants were reviewed at 4, 8 and 12 months corrected for prematurity at which time the history of rehospitalization was recorded and growth parameters were measured. RESULTS: Infants with BPD were found to have a higher overall rate of rehospitalization (58 vs 35%, relative risk (RR) 1.7, 95% confidence interval (Cl) 1.2-2.4) and were more likely to be readmitted for respiratory illnesses (39 vs 20%, RR 1.9, 95% Cl 1.1-3.2) and for poor growth (14 vs 1%, RR 14, 95% Cl 1.7-82) than the control group. Many infants, both study and control, remained below the 10th percentile at 1 year of age. More BPD infants were below the 10th percentile in weight at the 4 month visit than the control infants (30 vs 15%, P = 0.034). This difference was neither present at subsequent visits nor in the other major growth parameters. The 20 BPD infants who were on home oxygen therapy were more frequently hospitalized for concerns with failure to thrive (30 vs 9%, RR 3.3, 95% Cl 1.2 8.9) than the remaining 58 BPD infants. No significant differences were detected in the overall rate of rehospitalization. Poor growth at the corrected age of 1 year was similar in the two subgroups of infants. CONCLUSIONS: BPD infants are at increased for risk rehospitalization during the first year of life. While many infants with BPD have growth failure, it is suggested that the provision of appropriate supplemental oxygen at home may result in those infants having similar growth patterns when compared to birthweight matched preterm infants without BPD. PMID- 7794610 TI - The prevalence of respiratory symptoms in South Australian preschool children. I. Geographic location. AB - OBJECTIVE: This study was designed to ascertain the prevalence of respiratory symptoms in South Australian preschool children and to investigate the relationship between prevalence rates and geographic location. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the State preschool population of that age. At the time of a routine preschool health check, parents completed a questionnaire regarding their child's respiratory health and place of residence (postcode). RESULTS: Results showed that the prevalence rates were as follows: (i) ever having chest wheezing 38.6%; (ii) chest wheezing within the preceding 12 months 25.2%; (iii) ever having asthma 22.5%; (iv) ever having a dry cough at night 33.7%; (v) ever having bronchitis or cough with sputum 55.3%; (vi) ever having hay fever 29.7%; (vii) prone to excessive head colds 32.6%; and (viii) ever having eczema 18.8%. Over 38% of parents claimed that winter was the season for the most frequent or severe attacks of wheezing and 31.7% claimed no seasonal difference. Winter was the season most associated with episodes of bronchitis (50.9%), with no seasonal difference in episodes for 29.8% of children. Prevalence rates differed by geographic location within South Australia and within the Adelaide metropolitan region. CONCLUSION: This population-based survey shows that over 22% of South Australian 4 to 5 year old preschool children have had (or continue to have) asthma. The study also documented the geographic distribution of respiratory symptom prevalence within South Australia. PMID- 7794611 TI - The prevalence of respiratory symptoms in South Australian preschool children. II. Factors associated with indoor air quality. AB - OBJECTIVE: This study investigated the relationship between indoor air quality and the prevalence of respiratory symptoms in South Australian preschool children. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the targeted State preschool population. At the time of a routine preschool health check, parents completed a questionnaire regarding: their child's respiratory health and place of residence (postcode), parental smoking, type of fuel used for cooking and heating and method used for home cooling. RESULTS: For preschool children residing in the greater Adelaide region, logistic regression analyses found that having a natural gas stove compared to an electric stove was significantly associated with increased prevalence rates for: (i) asthma (odds ratio [OR] 1.24); (ii) wheezing in the preceding 12 months (OR 1.16); excessive colds (OR 1.14); and hay fever (OR 1.13). The use of a liquid petroleum gas stove compared to an electric stove was not associated with any respiratory symptoms. The use of a flueless gas heater compared to other forms of heating was significantly associated with increased prevalence rates for dry cough (OR 1.26), ever having wheezed (OR 1.15) and wheezing in the preceding 12 months (OR 1.18). The use of a wood fire/heater compared to other forms of heating was significantly associated with a reduced prevalence rate for dry cough (OR 0.84) and ever having wheezed (OR 0.82). Parental smoking was significantly associated with increased prevalence rates for bronchitis (OR 1.21) and ever having wheezed (OR 1.24). The form of home cooling used was not associated with prevalence rates, after accounting for geographic location. Socio-economic status (postcode level) was not generally associated with prevalence rates. CONCLUSIONS: These results suggest that respiratory symptom prevalence is related to the fuel used for cooking and heating and parental smoking. Prospective investigation regarding indoor air quality and respiratory symptoms is required. PMID- 7794612 TI - Trends in the use of fundoplication in children with gastro-oesophageal reflux. AB - OBJECTIVE: To document changing trends in the indications for fundoplication in children with gastro-oesophageal reflux and to identify the main shortcomings and complications of the procedure. METHODOLOGY: Retrospective review of 405 consecutive children undergoing fundoplication between 1978 and 1992 inclusive. RESULTS: Trends in the indications for fundoplication related to broadening of its use in those with severe neurological impairment and uncontrolled reflux, and to changes in the management of patients in the neonatal period. Complications included unwrapping with recurrence of reflux, hiatal hernia, adhesive small bowel obstruction, dumping syndrome, post-operative persistence of oesophageal stricture, excessively tight wrap and poor oesophageal clearance (mostly in oesophageal atresia patients). CONCLUSIONS: This study identified those patients most likely to develop complications following fundoplication. This may assist in the pre-operative assessment of the likely benefit of fundoplication in children who often have other complex problems. PMID- 7794613 TI - Efficacy of phototherapy for hyperbilirubinaemia in infants with the respiratory distress syndrome. AB - OBJECTIVE: To evaluate the efficacy of phototherapy for hyperbilirubinaemia in preterm infants with and without the respiratory distress syndrome (RDS). METHODOLOGY: Prospective cohort study of preterm infants cared for at Kandang Kerbau Hospital, Singapore: 170 with RDS and 477 without RDS, sepsis or other complications (control group) presenting with non-haemolytic hyperbilirubinaemia at about the same time were exposed to daylight phototherapy when bilirubin concentrations exceeded 255 mumol/L or 222 mumol/L if < 48 h of age. Bilirubin values were monitored 6-hourly during exposure, and daily for at least 2 days post-phototherapy. RESULTS: The infants were comparable in birthweight, gestational age, postnatal age, haemoglobin, haematocrit and bilirubin values, at start. The response to phototherapy of the infants with RDS was comparable to that of the well preterm infants; the duration of exposure was 50.1 +/- 1.6 (mean +/- s.e.m.) versus 50.1 +/- 1.4 h, 24-hour decline rate 25.71 +/- 1.29% versus 26.32 +/- 0.65, and overall decline rate 0.96 +/- 0.03%/h versus 0.95 +/- 0.02%/h. CONCLUSION: The presence of RDS did not affect the efficacy of phototherapy for neonatal hyperbilirubinaemia in preterm infants. PMID- 7794614 TI - Improving asthma documentation in a paediatric emergency department. AB - OBJECTIVE: To improve documentation for children presenting to the Emergency Department (ED) of The Children's Hospital with acute asthma. METHODOLOGY: In phase I, the documentation process was analysed using a standard total quality management (TQM) approach to identify specific problems leading to poor documentation. Fifty-two medical records of children presenting over a 3 week period were reviewed for nursing and medical documentation. A set of minimum criteria, consistent with the Paediatric Asthma Management Plan, were established for documentation by both medical and nursing staff. Following dissemination and education, compliance with documentation was evaluated and compared to an asthma survey performed in the ED in 1991. In phase II, a specific proforma for medical assessment was developed and 80 medical records of children presenting over a 3 week period were reviewed. Fifty-two (65%) with completed proformas were evaluated. The outcome measure was the documentation rate for minimum criteria established by TQM process. RESULTS: In phase I, nursing compliance with documentation ranged from 46% for signs of respiratory distress to 83% for a past history of asthma and 100% for pulse rate. Doctors were similarly poor at documenting essential elements such as severity (31%), palpable pulsus paradoxus (29%), the child's usual doctor (46%) and follow-up arrangements (21-56%). In phase II, the documentation of the severity of acute asthma (42%) and of the child's usual doctor (42%) remained poor but there were statistically significant improvements in documentation of interval medications, palpable pulsus paradoxus, respiratory rate, pre-treatment oximetry, education, follow-up arrangements and communication letters. CONCLUSION: The process of TQM has proved valuable in improving some aspects of documentation of children presenting to ED with acute asthma. It remains to be shown whether improved documentation will result in improved outcome. PMID- 7794615 TI - Retinopathy of prematurity in infants weighing 1000-1499 g at birth. AB - OBJECTIVE: To review the incidence and severity of retinopathy of prematurity (ROP) in infants with birthweights 1000-1249 g and 1250-1499 g, to establish whether the upper weight limit for routine ophthalmological examination might safely be lowered. METHODOLOGY: Prospective cohort study of infants born between 1 January 1977 and 31 December 1992 cared for in the neonatal nurseries at the Royal Women's Hospital, Melbourne. Data were retrieved on 1373 infants who survived their initial hospitalization. They comprised 657 with birthweights 1000 1249 g (group 1) and 716 with birthweights 1250-1499 g (group 2). There were 76 outborn infants in group 1 and 97 in group 2; the remaining infants were all born at the Royal Women's Hospital. Ocular examinations commenced at 2 weeks of age, when possible, and at 2-weekly intervals after that. RESULTS: In group 1, ROP was detected in 14.6% (96/657) and severe ROP (bilateral stage 3-5) in 5.0% (33/657). Five (0.8%) children required surgical intervention (reaching threshold disease); following surgery, one was legally blind, one had severely impaired vision, and the other three had near-normal vision. Another child was blind; he was born at 28 weeks gestational age with a birthweight of 1170 g, and was transferred to a Level II hospital at 9 weeks chronological age with no detectable retinopathy. He returned 1 year later totally blind with detached retinae (grade 5 ROP). The prevalence of bilateral blindness in this group was 0.3% (2/657). In group 2, ROP was detected in 6.4% (46/716) and severe ROP in 0.8% (6/716). No children required surgery; three were found to be myopic at follow-up but the corrected visual acuity was normal. No children in group 2 were blind. No significant difference was found between the rates of ROP in inborn and outborn infants. CONCLUSION: In neonatal units with similar rates of ROP and visual outcome, routine ophthalmological examination in the neonatal nursery of infants weighing more than 1249 g at birth is probably unnecessary. PMID- 7794616 TI - Another outcome of neonatal intensive care: first year mortality and hospital morbidity. AB - OBJECTIVE: To determine first year mortality and hospital morbidity after neonatal intensive care. METHODOLOGY: Cohort study of 6077 surviving infants inborn in one regional hospital in 1988. Nine hundred and eighty-eight received neonatal intensive care and 103 were very low birthweight (VLBW). RESULTS: For infants who required care in the neonatal intensive care unit (NICU), the relative risk of dying before their first birthday was 3.6 (95% confidence intervals [CI] 1.5-8.8). This increased risk was associated with low birthweight (LBW) rather than requirement for NICU care. Of all inborn survivors, 10.4% were readmitted to hospital in the first year and 2.4% more than once. The readmission rate was 20% for NICU survivors and 30% for VLBW infants. The risk of hospitalization was independently associated both with NICU admission (odds ratio 2.3, CI 1.9-2.9) and with VLBW (OR 1.8, CI 1.1-3.0). The NICU survivors also had multiple admissions and prolonged hospital stays. CONCLUSIONS: Both low birthweight and neonatal illness requiring intensive care are important indicators of continuing medical vulnerability over the first year of life. PMID- 7794618 TI - Somatosensory evoked potentials predict neurologic outcome in full-term neonates with asphyxia. AB - OBJECTIVE: To investigate the ability of somatosensory evoked potentials (SSEP) to predict neurologic outcome in term neonates with birth asphyxia. METHODOLOGY: Upper limb SSEP were performed on nine infants of 1-7 weeks of age who had perinatal asphyxia and an encephalopathy still present at 7 days of age. Comparison was made between the cranial ultrasound, electroencephalogram (EEG), SSEP and neurologic outcome at 9-36 months. RESULTS: Normal SSEP were found in four infants, all of whom were normal on neurologic follow up at 9-12 months. Neonatal EEG performed on two out of four of these infants were also normal, while cerebral oedema was seen on cranial ultrasound in three of the four studies. No SSEP response was seen initially in three infants, all of whom had adverse outcomes (one death, two with spastic diplegia). In contrast, their neonatal EEG had shown normal background rhythms, while two of the three cranial ultrasounds revealed oedema. For two infants the initial SSEP was absent over one hemisphere and just present over the other. Both children were abnormal on follow up at 10-12 months but did not have a hemiparesis. CONCLUSIONS: Upper limb SSEP appear more sensitive than EEG or cranial ultrasounds in predicting the short term neurologic outcome of neonates with asphyxia. PMID- 7794617 TI - Recommended body mass index cutoff values for overweight screening programmes in Australian children and adolescents: comparisons with North American values. AB - OBJECTIVE: Guidelines for screening children and adolescents for overweight have recently been published by a North American Expert Committee. As Australian clinicians might uncritically adopt these recommendations, we explore the consequences of applying North American body mass index (BMI) cutoff values to an Australian population. METHODOLOGY: The Australian BMI cutoffs were calculated using the methods recommended from height and weight data for 8492 schoolchildren aged 7-15 years old. RESULTS: Smoothed Australian BMI cutoffs were similar to those derived from the first United States National Health and Nutrition Examination Survey (NHANES-I) values for whites. However, the NHANES-I cutoffs would result in systematic misclassification. Among 7 year olds, the NHANES-I 85th percentile cutoff would wrongly classify 4.6% of normal males and 9.1% of normal females as 'at risk of overweight'. At age 14 years, the NHANES-I 95th percentile cutoff would misclassify 3.5% of children as 'overweight' instead of 'at risk of overweight'. CONCLUSION: Australian screening programmes should use BMI cutoffs appropriately derived from local measurements, and these are given for Australian children. PMID- 7794619 TI - Upper and lower gastrointestinal complications with dexamethasone despite H2 antagonists. AB - OBJECTIVE: To describe three preterm babies who developed gastrointestinal complications during treatment with dexamethasone for chronic lung disease, during a 10 month period. METHODOLOGY: Case reports in a tertiary neonatal intensive care unit. RESULTS: All three babies had received intravenous cimetidine since the commencement of steroid therapy, and developed gastrointestinal complications. There was no evidence of necrotizing enterocolitis in either of the two babies with gastrointestinal perforation. This is the first report of lower gastrointestinal complications associated with dexamethasone therapy. CONCLUSION: Recommendation of concomitant use of H2 antagonists with steroid therapy may be premature, and requires testing with a randomized controlled trial. PMID- 7794620 TI - Phenytoin in the management of severe acute SIADH. PMID- 7794621 TI - Infants and the prone position and its relationship to SIDS. PMID- 7794622 TI - ISPAD declaration of Kos. International Study Group of Diabetes in Children and Adolescents. PMID- 7794623 TI - ISPAD Declaration of Kos. International Society for Pediatric and Adolescent Diabetes. PMID- 7794624 TI - Survival of low birthweight infants in central Queensland. PMID- 7794625 TI - Experience with ACS for infantile SGS. PMID- 7794626 TI - Cyclical vomiting syndrome. AB - Cyclical vomiting syndrome is an uncommon, disabling symptom complex of unknown cause, with features in common with migraine. It affects principally children and adolescents. Differential diagnosis and theories of pathogenesis are discussed. Therapy should be aimed at prophylaxis of vomiting bouts, 'switching off' episodes once they commence and preventing complications of established vomiting episodes. Families need rapid access to care to minimize morbidity and disruption to functioning. PMID- 7794628 TI - Adherence to recommended medical regimens in childhood and adolescence. AB - OBJECTIVE: Factors that appear to influence treatment adherence among adults have been the focus of considerable research in recent years. However, less research has focused on children's treatment adherence. This paper reviews current knowledge about factors that appear to influence adherence among children and adolescents. METHODOLOGY: Factors associated with adherence to medical regimens reviewed here include: (i) the psychosocial characteristics of children and their parents; (ii) the nature of the treatment regimen; and (iii) the relationship between health practitioners, parents and paediatric patients. CONCLUSIONS: Issues for future research include: (i) the adherence of both children and their parents to children's treatment, and the allocation of responsibility for treatment adherence; (ii) the wide range of behaviours involved in regimen adherence should be acknowledge; patients' adherence to one aspect of their regimen should not be considered indicative of their overall adherence; and (iii) longitudinal studies are required to examine the causal relations between patient adherence and its antecedents. PMID- 7794627 TI - Predicting the outcome of symptomatic congenital cytomegalovirus infection. AB - The prognosis of babies with symptomatic congenital cytomegalovirus (CMV) infection is worse than for those with asymptomatic CMV, but is difficult to quantify. Babies affected as a result of primary maternal CMV are at greater risk than after reactivation CMV. Chorioretinitis occurs in 10-15% of symptomatic babies and almost always indicates significant mental impairment. Microcephaly occurs in around 50% at birth, but does not always persist, and does not necessarily imply later neurological handicap. Investigative findings that increase the likelihood of handicap include radiographic or computerized tomography scan finding of intracranial calcification and raised cerebrospinal fluid protein. Late deafness is always unpredictable and all babies with congenital CMV infection should have an audiological follow up. The mortality of symptomatic congenital CMV infection is about 30%. PMID- 7794629 TI - Recommendations for dietary intervention in the prevention and treatment of hyperlipidaemia in childhood. The Dietitians' Association of Australia and the Australian College of Paediatrics. PMID- 7794631 TI - Effects of nasal continuous positive airway pressure on apnoea index and sleep in infants. AB - OBJECTIVE: We examined the effectiveness of nasal continuous positive airway pressure (CPAP) for treatment of sleep apnoea in infants. METHODOLOGY: We studied five infants who all had significant central and mixed apnoea and severe sleep fragmentation. Polysomnographic recordings were performed on 2 consecutive nights in these infants. One night was used as a control study and during the second night nasal CPAP was applied throughout the night. RESULTS: Nasal CPAP significantly reduced apnoea in each infant, with the apnoea index (apnoeas/h) decreasing from 65.6 +/- 14.6 during the control study to 10.5 +/- 14.6 during CPAP in non-rapid eye movement (non-REM) sleep, and from 106 +/- 13.9 during the control study to 26.6 +/- 13.9 during CPAP in REM sleep. Nasal CPAP also improved the sleep fragmentation markedly; REM sleep increased from 14.2 +/- 1.2% of sleep during the control study to 27.1 +/- 1.2% of sleep during CPAP. CONCLUSIONS: We conclude that nasal CPAP is an effective treatment for infantile apnoea. Sleep apnoea in these infants is associated with profound sleep fragmentation, which is reversed by nasal CPAP. PMID- 7794630 TI - A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong. AB - METHODOLOGY: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major. RESULTS: Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4 +/- 0.1 mU/mL vs 0.37 +/ 0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 +/- 0.2 U/mL vs 0.56 +/- 0.14 U/mL, P = 0.26). CONCLUSIONS: Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major. PMID- 7794632 TI - Parental asthma knowledge: its association with readmission of children to hospital. AB - OBJECTIVE: To assess whether poor parental knowledge about asthma was a risk factor for readmission of their children to hospital. METHODOLOGY: Parents of children who were admitted to the paediatric facility at Newcastle Mater and John Hunter Hospitals were administered a previously validated asthma knowledge questionnaire with a maximum possible score of 31. RESULTS: The mean parental knowledge scores for three groups of children were determined: those with a previous diagnosis of asthma being readmitted to hospital (170 children, mean score 18.3); those with a previous diagnosis of asthma being admitted for the first time (114 children, mean score 17.2); and children being admitted with their first attack of asthma (65 children, mean score 15.6). There was a significant difference in parental asthma knowledge between the first and third group (P < 0.001) but not between the first and second group. A linear regression model with knowledge score as an outcome found that increased knowledge was associated with previously diagnosed asthma, higher parental occupation and no smoker in the home. CONCLUSIONS: Knowledge was poor in all groups. Readmission rate was related to the severity of the child's asthma. PMID- 7794633 TI - Clinical manifestations and outcome of Haemophilus influenzae type b disease. AB - OBJECTIVE: To document clinical manifestations, laboratory findings and outcome of childhood Haemophilus influenzae type b (Hib) infections. METHODOLOGY: Medical records of 235 children with Hib disease admitted to hospital during a 2 year period were reviewed; additional information was obtained by questionnaire and follow up 6 weeks after discharge. RESULTS: Three-quarters of patients presented with either meningitis or epiglottitis. Children with epiglottitis were older, had shorter illnesses and were less likely to have had antibiotics before admission than those with meningitis; 38% of the latter had been given some antibiotic therapy, with no apparent effect on the outcome. Fever persisted for 7 days or more in 23% of patients with meningitis. Death from meningitis occurred in 3.8% of patients and was due to fulminating disease. CONCLUSIONS: These data will assist in recognition and appropriate management of Hib disease as the clinical manifestations become less familiar following the introduction of immunization. Specific laboratory diagnosis is required for accurate surveillance, which should be maintained in order to ensure high immunization rates. PMID- 7794634 TI - [Course of histological lesions of the gastric mucosa after eradication of H. pylori in patients with duodenal ulcer. Initial study and 6-month follow-up]. AB - Helicobacter pylori is the major etiologic agent of chronic active gastritis, and it may be isolated from the gastric mucosa in a high proportion of patients with duodenal ulcer. AIM: To study, in duodenal ulcer patients, the histological changes associated with H. pylori infection in gastric antrum and body, and the improvement of such lesions after eradication, at an early stage and after 6 months. METHODS: 76 patients with duodenal ulcer disease were investigated prospectively. Biopsy specimens taken by endoscopy from the duodenal bulb, antrum, body and gastric fundus were analyzed by microbiological and histological methods. A patient was considered to be H. pylori-positive when microbiology or/and histology demonstrated colonization in any of the locations. An endoscopy with biopsy samples from the antrum and gastric body was performed 1 month after therapy and 4 months later. Different therapy regimens were used: amoxicillin/clavulanic plus omeprazole or ranitidine; triple therapy; and omeprazole or ranitidine alone. RESULTS: All patients were positive by microbiology. Eradication was reached as a whole in 47% (N = 36). In those patients, in gastric antrum, rates of chronic gastritis/chronic active gastritis previous to treatment and 2 and 6 months later were 100%/96%; 38%/23% and 16%/5.6% respectively. At gastric body they were: 54%/38%; 12%/12% and 12%/5.6% respectively. A favourable histologic evolution, globally and of the acute inflammatory component, was observed 1 month after therapy (p < 0.001). Six months later, there was further improvement which did not reach a statistically significant difference compared with the results obtained at the first month. No differences were observed when eradication failed. CONCLUSION: An improvement of antral and gastric body gastritis is associated with H. pylori eradication in duodenal ulcer patients. This successful evolution is observed immediately after eradication, and it is confirmed six months after the diagnosis. PMID- 7794636 TI - [Is there a relationship between cholelithiasis and colorectal cancer?]. AB - PROBLEM: The pathogenesis of colorectal cancer must be perceived as a complex interaction between the genetic make-up of the individual and the environment. Recent publications stress the association between colorectal carcinoma and cholelithiasis. OBJECTIVE: A retrospective study was set up to compare the presence of cholelithiasis/cholecystectomy in patients with colorectal carcinoma vs gastric carcinoma. PATIENTS: In 481 patients with colorectal carcinoma, and in another group of 126 patients with gastric carcinoma, the incidence of prior cholelithiasis/cholecystectomy was investigated. RESULTS: In the colorectal carcinoma cases a personal history the cholelithiasis was observed more often than cholecystectomy, 88 vs 8 (P < 0.001) patients, and cholelithiasis was more commonly observed in cases of right-sided colonic cancer, than in cancer of the left colon and rectum. In the group with gastric carcinoma the cholelithiasis incidence was 5.6 percent. CONCLUSIONS: These findings suggest that a relationship was found more often between colorectal cancer and cholelithiasis, that with cholecystectomy. PMID- 7794635 TI - [Administration of growth hormone enhances the intestinal adaptive response after resection of small intestine in rats]. AB - The aim of this study was to assess the proliferative effect of growth hormone (GH) on the remnant intestinal mucosa after small bowel resection in the rat. Three groups (n = 8/group) of adult Wistar rats were established as follows: 1) control, 2) 90% small bowel resection (SBR) and 3) 90% small bowel resection + GH 1 mg/kg-day (SBR+GH) during 7 days. Ileal samples were taken prior to resection (basal), and at sacrifice, for assessment of intestinal mucosal growth by means of morphometric (crypt and villous length) and proliferative (proliferating cell nuclear antigen, PCNA) techniques. GH administered to resected rats (SBR+GH) significantly increased the number of proliferating cells and crypt and villous length when compared to resected non-treated animals (SBR). In conclusion, in the rat, GH markedly increases the trophic action of intestinal mucosa in hyperproliferative states like massive bowel resection, enhancing remnant bowel morphologic and proliferative adaptation. PMID- 7794638 TI - [Emergency laparoscopy. A 20-year experience]. AB - We revised 7988 laparoscopies over twenty years. Three hundred and ninety three were urgent laparoscopies: 325 patients with acute spontaneous abdomen and 68 acute traumatic abdomen. Emergency laparoscopy is made in patients with, both spontaneous and traumatic acute abdomen, when diagnosis is not made in 8 hours with the usual clinical and imaging methods. Acute diffuse peritonitis was the commonest finding in the first group (21%) and splenic rupture in the traumatic group (34%). There were two severe complications (0.5%): pulmonary oedema in a patient with myocardial disease and a respiratory failure in a old patient, which were resolved. We had two deaths related to laparoscopic diagnosis: massive mesenteric thrombosis and fecal peritonitis. There are few contraindications and tolerance is very good. This study shows a sensitivity of 98%, a specificity of 90%, a predictive positive value greater than 98% and a negative predictive value of 100%. In summary, the present study demonstrates that emergency laparoscopy is a effective diagnostic method in acute abdominal pain of uncertain aetiology. PMID- 7794637 TI - [Sensitivity of the anal canal: study techniques and results in normal subjects]. AB - AIM: To describe a technique for the study of the anal canal sensitivity to electric and thermal stimulation, and to investigate it prospectively in normal subjects. EXPERIMENTAL DESIGN: Mucosal electrosensitivity and thermal sensation of the anal canal is correlated with motor parameters: perineometry, manometry and electrophysiology. PATIENTS: 41 control subjects (20M & 21F) with normal anorectal anatomophysiology. RESULTS: In the middle anal canal minimum electrosensibility thresholds were present, and they were similar to the thermal profile. A significant impairment in electrosensitivity was observed as a function of age, but no differences between the sexes were found. Lower thresholds were obtained than cold temperatures (p < 0.001). Both tests of sensitivity correlated with pudendal motor parameters. The maximal thermal difference in the anal canal was 0.28 degree C, while the minimal detectable temperature change was 0.46 +/- 0.1 degrees C. CONCLUSIONS: The sensitivity of the anal canal is greatest in the zone of the anal valves and better in response to hot than cold stimulus. As the minimum detectable temperature change has been greater than the difference of temperature between the low and high anal canal, we suggest that discrimination is not possible on the basis of thermal differences. PMID- 7794639 TI - [Gastrointestinal diseases causing hematologic changes]. PMID- 7794640 TI - [Undifferentiated small cell (oat cell) carcinoma of the esophagus]. AB - A case of small cell carcinoma (oat cell) of the esophagus is presented. Esophagectomy and gastroplasty were performed followed by six cycles of combination chemotherapy and radiotherapy. Recovery was uneventful. The patient died nine months later with widespread disease. Literature is reviewed. To date, about 100 cases of this rare tumor have been reported. The aggressive behavior of the tumor is stressed and the different therapeutic modalities are discussed. PMID- 7794641 TI - [Gastric cavernous hemangioma as a cause of upper digestive hemorrhage]. AB - Upper digestive bleeding caused by an isolated gastric hemangioma is a rather rare occurrence, even in cases of Osler-Weber-Rendu syndrome. The case reported here, which brings to 40 the number reported in the world literature, is that of a 68-year-old patient who presented with upper digestive bleeding. Endoscopy led us to suspect a hemangioma due to the abnormally large lesion, a suspicion that was confirmed preoperatively through arteriography, which detected a hypervascular mass of 6 x 4 cm dependent on the gastroduodenal artery. This finding was in turn confirmed by the surgical intervention. Diagnostic difficulties based on barium studies, endoscopy and surgical exploration have meant that preoperative diagnosis has been rare in the cases published to date. We consider that a more liberal use of arteriography could reverse this tendency, as indeed our case has shown. Furthermore, we feel that arteriography is indicated in cases of upper digestive bleeding of obscure origin, which might be due to small angiomas that may be overlooked in other diagnostic tests. PMID- 7794643 TI - [Appendiceal Crohn's disease]. AB - Crohn's disease of the appendix is an uncommon process that is more frequent in young people. The most common preoperative diagnosis is acute appendicitis. At exploratory laparotomy the appendix is enlarged and malignancy may be suspected. The differential diagnosis may be difficult. Serologic tests and cultures should be performed to exclude Yersinia infections. Appendicectomy is a safe procedure when the disease is limited to the appendix. The postoperative course is usually uncomplicated with a low rate of complications and recurrence. Although it may be a different process than Crohn's disease and the recurrence rate is low, it is suggested that all the patients should be followed-up so that recurrences may be recognized and treated as early as possible. A new case is presented after two years of follow-up without recurrence. PMID- 7794642 TI - [Familial hyperphosphatasemia of intestinal origin]. AB - To clarify the diagnostic laboratory procedures before a case of unknown origin hyperphosphatasemia, we have studied the electrophoretic separation of serum alkaline phosphatase activity on agarose gel with and without neuraminidase. Sera were collected from a family, four of whom showed hyperphosphatasemia. Alkaline phosphatase isoenzyme patterns on agarose gel electrophoresis demonstrated that two persons out of the six members tested had unusual isozymes, the hydrophilic and the hydrophobic intestinal isozyme representing more than 50% of total alkaline phosphatase. The advantages of this method are its simplicity and low cost. The early recognition of this benign abnormality should help to avoid unnecessary diagnostic tests (i.e. image or radioisotopic examination). PMID- 7794644 TI - [Inguino-crural hernia with neoplastic content]. AB - We report a case of incarcerated crural hernia including omentum with metastases of pancreatic carcinoma. The scarce literature is reviewed. The possibility of mistaking an incarcerated crural hernia for an inguinal lymph node may result in a ganglionar biopsy ending up in a crural herniography under local anaesthesia. We recommend that all hernial sacs be examined, especially those of adult patients and, in such cases, a crural herniography with prolene should be made in view of its remarkably technical simplicity. PMID- 7794645 TI - [Pancreatic ascites and octreotide]. PMID- 7794646 TI - [Somatostatin in refractory pancreatic ascites]. PMID- 7794647 TI - [Perianal cutaneous metastasis of rectal adenocarcinoma]. PMID- 7794648 TI - Celebrating our 30th anniversary as nurse practitioners and our 10th anniversary as an academy. 1973. PMID- 7794649 TI - Representative Edolphus Towns (D-New York). Interview by Carole Jennings. PMID- 7794651 TI - The beta-2 agonists. PMID- 7794652 TI - An economic analysis of AIDS--towards a proposed model of costing: a Singapore experience. AB - With the increasing prevalence of HIV infection/AIDS and the extending range of care and treatment, the economic implications of the various prevention and control strategies, and of treatment, have become the subject of interest to policy-makers, public health specialists and health economists. This paper presents an overview of the methods used for the economic analysis of AIDS/HIV infection. It proposes an activity-oriented, cost center-based model for the costing of the economic impact of AIDS, using cost figures in Singapore since 1985, when the National AIDS Control Program was started. Priorities for future research are also identified. PMID- 7794650 TI - The moral reasoning of nurse practitioners. AB - This qualitative research study was conducted to describe the moral reasoning utilized by participating nurse practitioners to resolve moral dilemmas in their clinical practice. Five major essential features of moral reasoning emerged from the data: the contextual framework for moral reasoning, values, influencing factors, recognizing the dilemma, and outcomes. The interrelationship of the essential features of moral reasoning provided insight into how NPs deal with moral dilemmas as well as the role that caring and the nurse-patient relationship played as a part of the moral decision making process. PMID- 7794654 TI - A comparative study on the efficacy of a mass screening program for colorectal cancer--comparison between cancer cases detected by mass screening and by outpatient clinics. AB - The present study was carried out to investigate the efficacy of colorectal screening through a comparison of the characteristics of the cancer cases detected by screening programs and by outpatient clinics. A total of 78 cases with colorectal cancer diagnosed by screening programs using fecal occult blood test in Nagano Prefecture, Japan, was collected as the index group and the same cases (one matched cases) diagnosed through outpatient clinics served as the control group for the present study. A comparison of various factors, such as tumor site, Dukes' stage, histological type, and survival rate, was made between the index and control groups. No differences were noted in tumor site and histological type between the two groups examined. The proportion of early cancer and the survival rate, however, were significantly higher in the index group than in the control group (p < 0.01). These results suggest that colorectal screening is an efficient preventive measure. PMID- 7794656 TI - Denver Developmental Screening Test survey of Bangkok children. AB - A preliminary developmental survey (using DDST) of 1442 Bangkok children who were between the ages of two weeks and six years was conducted between June 1983 and December 1987. The results of this study showed that the 25th percentile for the development of Bangkok children in the areas of personal-social, fine motor adaptive, language and gross motor skills were comparable to the children in original samples in Denver. Although the Bangkok group seems to have passed many test items at earlier ages, the 75th-90th percentile in each test item was generally more delayed in the Bangkok group. The investigative team suggests that further research for the purpose of establishing a norm for the DDST be pursued on the basis of geographical sampling more than socioeconomical sampling that was used in this study. PMID- 7794655 TI - Health status comparison by urinalysis (dipstick test) among four populations in Papua New Guinea. AB - The health status of four populations depending on traditional subsistence in Papua New Guinea was compared by the dipstick test urinalysis. Conspicuous inter population difference in the distribution of urinary pH was attributed to the levels of protein intake and the balances of sodium and potassium intake. The percentage of positive findings on protein differed by population along with the percentages of urobilinogen and bilirubin; the higher percentage of protein positives (12-16%) found in less urbanized populations suggests a high risk of hepatic and/or renal disorders in traditional societies. The very low percentage, 0.3 percent, of positive findings on glucose among 1,132 urine samples tested indicated that diabetes mellitus was not yet the major problem. Simultaneously, however, the fact that glucose positives were found only in the most urbanized villages indicates increasing risk of diabetes even in the traditional populations during future urbanization. PMID- 7794653 TI - Maternal and child health in urban Sabah, Malaysia: a comparison of citizens and migrants. AB - This paper describes selected maternal and child health indicators based on a cross-sectional study of citizens and migrants in Sabah, Malaysia. A total of 1,515 women were interviewed from a multi-stage random sample of households in eight urban centers. Among the 1,411 women in the sample who had experienced a pregnancy before, 76% were local citizens and 24% were migrants. There were statistically significant differences between citizens and migrants in ethnicity, religion, education, household income, and access to treated water supply and sanitary toilet facilities. Significantly fewer migrants practiced any form of contraception and obtained any antenatal care during any pregnancy. Furthermore, citizens tended to initiate care as early as three months but migrants as late as seven months. Despite these differences, only the infant mortality rate, and not pregnancy wastage, was statistically significantly higher among migrants. Pregnancy interval was also similar between the two groups. The influence of several socioeconomic factors on pregnancy wastage and infant mortality was explored. PMID- 7794658 TI - Establishment of an International Information Network for International Health Development: a survey of public health administration and management courses. AB - The purpose of the present study was to examine the content emphasis of courses of public health administration and management (A & M) among member institutions of the Asia-Pacific Academic Consortium for Public Health (APACPH), to determine comparability of curricula across campuses. A survey of course syllabi from APACPH schools was conducted by three separate reviewers to identify topical subject matter presented in general and specialty A & M courses delivered to graduate students at each campus. Based on this review, three synthetic general content A & M courses, and one specialty A & M course (i.e. Hospital Administration) were created as a basis for intercampus cross-institutional comparisons conducted by the author. Despite the number of courses provided by the different APACPH institutions, specific content areas consistently appeared across institutions, suggesting possible foundational A & M content for public health students. In general, there was much better coverage of similar topics at the introductory level of instruction, and much greater consistency was observed across institutions that provided course work addressing the administration of hospitals. Several recommendations are made for further studies of other content areas, and for the development of minimum training content areas as a basis for cross-institutional studies. PMID- 7794657 TI - Health practices and indices of a poor urban population in Indonesia. Part I: Patterns of health service utilization. AB - This first section in a two-part study of health indices and practices among residents living in a Jakarta slum describes the use of public and private primary health care services in relation to socioeconomic and health status. As problems associated with urban poverty rapidly increase in developing countries, it is important to study the ethnic and economic diversity which exists in slums and shanty towns: results of such studies should inform the development of effective strategies for outreach and service delivery. Through a survey of 690 mothers and 593 children, we found that 1) poorer residents were more likely than relatively affluent ones to rely on local government clinics (posyandus) for primary health care; 2) regular posyandu users were more likely than non-users to be fully immunized and to use ORT correctly; 3) delivery in hospital was common among all residents, but especially among the more affluent; and 4) prevalence of contraception was high and not associated with socioeconomic status or type of primary health care service used. Strengthening primary health care services at the government's local health posts could benefit all groups in the community if wealthier residents participated more in the posyandus. Standards of care in the private sector should also be improved. PMID- 7794659 TI - Knowledge and use of maternal and child health services by mothers in Papua New Guinea. AB - A survey was conducted in the coastal area of Morobe Province in Papua New Guinea between March to April 1992 in order to obtain and examine the current health knowledge and practices of mothers with children under two years of age. The purpose of the survey was to gather data for the detailed planning and implementation of a Child Survival Intervention Project funded by USAID. A total of 30 villages in the area were selected utilizing the WHO 30-cluster sampling technique. The results indicated that breastfeeding was a very common practice. However, because nutritional intake was not increased during pregnancy and lactation for many of the women, it is likely that their nutritional intake was insufficient. Although many mothers knew the importance of immunization, they were unclear about the importance of completing immunization series. The utilization of contraceptive methods was very low among women who did not want to have another child within the subsequent two years. The most common methods were injections and pills. The dissemination of health education to isolated rural villages is one of the most important interventions in reducing maternal and infant mortality. As there currently is no health education unit at the Morobe Provincial Department of Health. It is crucial to establish the unit and to emphasize the importance of health education as the tool for disease prevention and health promotion. PMID- 7794660 TI - Asia-Pacific Academic Consortium for Public Health (APACPH) representatives, member institutions, and addresses December 1994. PMID- 7794662 TI - The awesome possibilities of CD-ROM. PMID- 7794661 TI - Creating the conditions for healing and health: the challenge of patient care executives. PMID- 7794663 TI - New partnerships in care delivery: three hospitals and a school district combine their resources to deliver prenatal care. PMID- 7794664 TI - Nurse executives on-line: connecting to on-line services. Bulletin boards and the Internet--Part I. PMID- 7794665 TI - Downsizing: the nurse executive's roles and responsibilities. PMID- 7794666 TI - Social responsibility in the health care marketplace. PMID- 7794667 TI - Management prerogatives versus nurses' free speech: new precedents. PMID- 7794668 TI - Integrating ethical principles into operational decision making. PMID- 7794669 TI - False-negative surgical margins. PMID- 7794670 TI - Identification of those at highest risk for development of malignant melanoma. AB - Multiple factors have been identified to be associated with increasing risk for MM developing. These factors are summarized in Table 2. As the incidence of MM continues to rise and the magnitude of this problem becomes more significant, the issue of identifying those at increased risk for MM developing in the future will become even more important. PMID- 7794671 TI - Melanoma and Mohs' micrographic surgery. PMID- 7794672 TI - The clinical and biologic basis for radiation therapy of cutaneous carcinoma, melanoma, and lymphoma. PMID- 7794673 TI - Choosing the correct surgical instruments. PMID- 7794674 TI - Pain management for dermatologic procedures in children. AB - Simple explanations provided to children and their parents before a dermatologic procedure is attempted will decrease the time it takes to perform the procedure and make it a less difficult experience for all concerned. The dermatologist should always consider the availability of less painful but effective methods when treating children. PMID- 7794675 TI - A 10-year retrospective on Advances in Dermatology. PMID- 7794676 TI - Juvenile dermatomyositis and overlap syndromes. PMID- 7794677 TI - Life-threatening dermatoses in pediatric dermatology. PMID- 7794678 TI - Pruritus in the elderly. PMID- 7794679 TI - Molecular mechanisms of skin aging. AB - At the cellular and molecular levels, the limited ability of aged fibroblasts and keratinocytes to respond to changes in their environments fits nicely the concept of aging as inability of the organism to respond adaptively to environmental changes. Whether these molecular changes represent cumulative random genetic damage or programmed aging process cannot be determined. Nevertheless, the data correlate with the well-known differences in biologic responsiveness between newborn, young adult, and old adult cells. Thus, our findings represent a beginning from which more comprehensive understanding of molecular changes involved in cutaneous aging will evolve. PMID- 7794680 TI - Wound healing. AB - Wound healing is a dynamic biologic process of repairing insults to the integumentary system. It is commonly divided into three phases: inflammatory, proliferative, and maturation. Each phase has unique cellular and substance constituents without which it cannot progress normally. A large variety of factors may influence any part of wound healing, including local factors such as bacteria, oxygen tension, and bleeding, and systemic factors such as the mental and physical health of the patient. There are also extrinsic factors that can be influenced by the caretakers of the wound to enhance wound healing. Areas of intervention include using antiseptic technique when one is dealing with the wound, using good surgical technique, choosing the appropriate wounding method and repair for the individual patient, and using antibiotics and special wound dressings. Modern science and technology are giving us new insights into wound healing and leading us to exciting new ways of influencing it, including the topical use of growth factors, artificial skins, cultured epithelium with and without dermal components, and electrical stimulation. The future of wound healing holds a better understanding of the complexities of the physiologic events that occur and a translation of that into a biologically active and interactive wound care. PMID- 7794681 TI - Cytokine and genetic regulation of psoriasis. PMID- 7794682 TI - Phosphoinositidase C beta 1 isoform expression is modulated by interferon alpha in Burkitt lymphoma cells. AB - The expression of phosphoinositidase C (PIC) at nuclear and cytoplasmic level has been revealed in control and interferon treated Burkitt lymphoma cells by means of western blotting and immunocytochemical analysis employing specific monoclonal antibodies against beta 1, gamma 1 and delta 1 isozymes. Results have indicated that PIC isoform beta 1, mainly detectable in the nucleus, undergoes transient modifications early after interferon treatment. PIC delta 1 has been found only at cytoplasmic level, apparently insensitive to interferon treatment, while PIC gamma 1 was scarcely or not detected either in the cytoplasmic or in the nuclear compartment. These results suggest that interferon may exert its antiproliferative effect activating at least two distinct pathways of signal transduction, at cytoplasmic and nuclear level, involving inositol lipid cycle mainly in the nucleus by modulation of PIC beta 1 expression. PMID- 7794683 TI - Dissociation of phosphatidylinositol-3 kinase activity and mitogenic inhibition in vascular smooth muscle cells. AB - Phosphatidylinositol-3 kinase becomes activated upon association with stimulated tyrosine kinase coupled receptors, but it is also catalytically active in platelets incubated with the G-protein coupled growth factor receptor agonist, thrombin. Furthermore, phorbol esters have been shown to be growth inhibitory when added to vascular smooth muscle cells simultaneously with thrombin. In order to clarify the role of phosphatidylinositol-3 (PI-3) kinase in thrombin-induced mitogenesis, we asked whether PI-3 kinase activity is decreased in parallel to mitogenesis in cells stimulated with phorbol-12-myristate-13-acetate (PMA) and thrombin. Although PMA inhibits thrombin-stimulated growth by 92% when the two compounds are added simultaneously, the level of PI-3 kinase activity under similar conditions is not decreased. This phenomenon is independent of protein kinase C, since there is no difference in PI-3 kinase activity when similar experiments are performed after protein kinase C is down-regulated by 24 h pre incubation with PMA. We conclude that either (i) PI-3 kinase is not required for the mitogenic signalling of thrombin, or (ii) PMA is acting downstream of PI-3 kinase in thrombin's signalling pathway. PMID- 7794684 TI - The effect of thrombin and serine proteases on intracellular Ca2+ in rat aortic smooth muscle cells. AB - Cultures of vascular smooth muscle cells (VSMC) are commonly used to study the events and defects found in hypertension and atherosclerosis. In particular Ca2+ homeostasis in cellular signalling has been the focus of extensive research. Since trypsin has been shown to mobilise Ca2+ in some cell types, we have investigated its effect on various aspects of Ca2+ homeostasis in rat aortic smooth muscle cells (RASMC). The effects of trypsin, alpha-chymotrypsin and elastase (other serine proteases) on intracellular Ca2+ in cultured aortic cells isolated from Wistar rats have been investigated. Trypsin (24 micrograms/ml) elicits intracellular Ca2+ mobilisation, after which cells become nonresponsive to thrombin Ca2+ mobilisation but retain responsiveness to Angiotensin II (AII). alpha-Chymotrypsin (24 micrograms/m) inhibits the thrombin Ca2+ mobilising response, without itself initiating a Ca2+ transient or affecting AII Ca2+ mobilisation. Elastase (24 micrograms/ml) was not effective in mobilising intracellular Ca2+ or inhibiting the thrombin response. We have also observed diminished thrombin Ca2+ mobilisation responses between cells in suspension and cell monolayers, which appeared to be unrelated to proteolysis but due to morphological changes of the cells. Our results suggest that trypsin acts on the thrombin receptor via a specific proteolysis mechanism to mobilise intracellular Ca2+ ([Ca2+]i) in RASMC. The amount of Ca2+ released by thrombin or trypsin is dependent on the morphology of the cell and the state of the tethered ligand of the thrombin receptor exposed by the protease. PMID- 7794685 TI - Actions of isoproterenol in frog proximal tubules. AB - In the present work, we compared biochemical and electrophysiological actions of isoproterenol on frog proximal tubular cells by using tubule suspensions and giant entities obtained by cell fusion. Isoproterenol (ISO) dose-dependently stimulated cAMP production in tubule suspension and depolarized the "giant cell" membrane. Both effects were triggered by beta receptor occupancy, but strongly differed in their concentration-dependency, since depolarization occurred with an ISO concentration as low as 10(-12) mol/l whereas cAMP accumulation could be seen only with more than 10(-8) mol/l ISO. ISO-induced membrane depolarization was mimicked by forskolin which directly stimulated the catalytic subunit of adenylyl cyclase. In both isoproterenol- and forskolin-stimulated giant cells, membrane depolarization was accompanied by a decrease in membrane conductance, and both effects were inhibited by tetraethylammonium (TEA) and 4-aminopyridine (4-AP). On the other hand, ISO- and forskolin-induced cAMP production were not affected by TEA. The present data thus show that isoproterenol produces two independent effects in frog proximal tubule: it depolarizes the cell membrane by blocking a K+ conductance and activates adenylyl cyclase. PMID- 7794686 TI - EGF causes hyperproliferation and apoptosis in T51B cells: involvement of high and low affinity EGFR binding sites. AB - We have recently described an in vitro model for liver homeostasis which involves growing T51B rat liver epithelial cells with 1 nM epidermal growth factor (EGF). There is an initial period of hyperplasia, lasting about 3 days, which is followed by an increase in apoptosis. The cell density returns to around the confluent control level 5 days after EGF addition. The dose response of T51B cells to EGF shows three distinct growth patterns. We have carried out EGF binding studies that suggest that the occupancy of the low affinity binding site of the EGF receptor, is responsible for the hyperproliferation seen when the cells are grown with high doses of EGF. These studies also suggest that the apoptosis could be triggered by down-regulation of the receptor, in a manner analogous to the removal of a trophic hormone in other systems. PMID- 7794687 TI - G-receptor antagonists increased the activating effect of mastoparan on low Km GTPase of mouse PAG. AB - Mastoparan activated in a concentration-dependent manner the low Km GTPase activity in P2 fractions from mouse periaquedultal grey matter (PAG). This peptide at 1-10 mM produced increases of 30-70% over the basal value of 90-120 pmol Pi/mg/min. A series of substances displaying antagonist activity at cellular receptors and not modifying the GTPase function, when used at nanomolar and micromolar concentrations enhanced the effect of mastoparan upon this enzyme. These included antagonists of receptors coupling G proteins: naloxone (non selective opioid antagonist), CTOP (m opioid receptors), ICI 174,864 (d opioid receptors), nor-BNI (k opioid receptors), sulpiride (D2 dopaminergic antagonist), idazoxan (a2 adrenergic antagonist). Bicuculline, antagonist of a receptor not linked to G proteins, GABAA, did not alter the effect of mastoparan on the GTPase. The m opioid agonist, DAMGO, prevented naloxone from increasing the function of the mastoparan-activated enzyme. Thus, mastoparan appears to act on Gi/Go proteins at a site not directly related to the receptor binding domain. PMID- 7794689 TI - Structural and functional heterogeneity of insulin receptors. AB - It was long believed that the effects of insulin are mediated by a unique insulin receptor. However, there is considerable evidence suggesting that insulin receptors in brain, liver, adipocytes, and lymphocytes are heterogeneous in structure and function. This evidence is based on comparisons of concentration response curves in cells and tissues, and on comparisons of binding and effects of insulin-derivatives and receptor antibodies. Two receptor isoforms (IR-A and IR-B) generated by alternative mRNA splicing have been identified, but cannot fully account for the observed differences in ligand binding and receptor function. It is suggested that the differences in ligand binding reflect yet to be defined post-translational modifications, and that post-receptor events are responsible for the observed heterogeneity of insulin action. PMID- 7794688 TI - The inhibition of adenylyl cyclase activity in isolated lung membranes by muscarinic and alpha-adrenoceptor agonists: role of G-protein alpha and beta gamma sub-units. AB - Forskolin (10 microM) failed to abolish the GppNHp- (0.1 nM) dependent inhibition of adenylyl cyclase activity in isolated membranes. Whilst clonidine (1 microM), an alpha 2-adrenoceptor agonist, inhibited adenylyl cyclase activity it did not protentiate the GppNHp-dependent inhibition. This indicates that low concentrations of the guanine-nucleotide activate sufficient Gi to inhibit adenylyl cyclase activity maximally and that clonidine inhibits this enzyme via a similar route. These data support a role of alpha i sub-unit inhibition of adenylyl cyclase activity. In contrast, forskolin (10 microM) abolished the GppNHp (0.001-0.1 nM) dependent inhibition of adenylyl cyclase activity in membranes where adenylyl cyclase activity is limited, i.e. where activity has been depleted by approximately 80%. In this case, inhibition of adenylyl cyclase by beta gamma sub-units is implicated and only becomes evident under these conditions. Adenylyl cyclase is also inhibited by muscarinic receptor agonist, methacholine and by the alpha 2-adrenoceptor agonists, clonidine and nor adrenaline. Both classes of agonist also elicit an increase in the cholera toxin catalysed ADP-ribosylation of the splice variant forms of Gs alpha and of a polypeptide of 41,000 M(r). The ADP-ribosylation of the 41,000 M(r) polypeptide is inhibited by GTP (100 microM) and therefore displays characteristics similar to Gi alpha. Muscarinic receptor and alpha 2-adrenoceptor agonists appear to inhibit adenylyl cyclase activity in lung membranes predominantly via Gi alpha. Lung expresses both type II and IV adenylyl cyclase which are stimulated by direct interaction with beta gamma sub-units and this is conditional upon the co incident activation of Gs alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794690 TI - Calcium, calmodulin and cell cycle progression. AB - Proliferation of mammalian cells both in vivo and in vitro is dependent upon physiological concentrations of extracellular Ca2+. Growth factor stimulation of quiescent cells at the G0/G1 border usually results in a rapid mobilization of Ca2+ from both intra- and extracellular pools. However, Ca2+ influx is also required for later phases of cell cycle transition, especially in the late G1 phase for initiation of DNA synthesis. Available evidence indicates that calmodulin plays the major and essential roles in the Ca(2+)-dependent regulation of cell proliferation. Ca2+ and calmodulin act at multiple points in the cell cycle, including the initiation of the S phase and both initiation and completion of the M phase. Ca2+ and calmodulin stimulate the expression of genes involved in the cell cycle progression, leading to activation of cyclin-dependent kinases p33cdk2 and p34cdc2. Ca2+ and calmodulin are also involved in activation of enzymes participating in nucleotide metabolism and DNA replication, as well as nuclear envelope breakdown and cytokinesis. Ca2+/calmodulin-dependent protein kinase II and protein phosphatase calcineurin are both involved in the Ca2+ and calmodulin-mediated signalling of growth regulation. As compared to normal cells, growth of transformed cells is independent of extracellular Ca2+ and much less sensitive to calmodulin antagonists, suggesting the existence of derangements in the Ca2+ and calmodulin-mediated growth regulation mechanisms. PMID- 7794691 TI - A new approach in exciton-coupled circular dichroism (ECCD)--insertion of an auxiliary stereogenic center. AB - There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3 hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH = C = CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. PMID- 7794692 TI - Macromolecular ionophores. 1. Chiral recognition properties of poly[(1-->6)-2,5 anhydro-D-glucitol] toward racemic amino acid ester. AB - The chiral recognition property of poly[(1-->6)-2,5-anhydro-3,4-di-O-alkyl-D glucitol] (1) toward racemic RCH (CO2CH3)NH3+.PF6- (2.HPF6) has been studied using a transport system involving an aqueous source and receiving phases separated by a chloroform phase containing 1. Transport rates for aromatic guests 2a (R = Ph) and 2b (R = CH2Ph) were faster than those for aliphatic guests, 2c (R = CH(CH3)2) and 2d (R = CH2CH(CH3)2), using the polymer substituted with methyl groups (1a). The enantiomeric excess (e.e.) was 10.9% for 2a as a maximum value and decreased in the order of 2a > 2c > 2b = 2d. When the transport of 2a.HPF6 was carried out using the polymers with 3,4-di-O-methyl (1a), ethyl (1b), allyl (1c), and pentyl (1d) groups, the e.e. was 22.0% for 1d as a maximum value and increased in the order of 1a < 1b < 1c < 1d. The formation of a complex between 1a and 2a.HPF6 was confirmed by 1H and 13C NMR spectral measurements. PMID- 7794693 TI - Myocardial uptake kinetics of tocainide enantiomers in the isolated perfused rabbit heart. AB - The extent of myocardial accumulation of tocainide, administered as single enantiomers and as well as racemate, was determined in the isolated, spontaneous beating rabbit heart. The heart was retrogradely perfused at a constant rate and fractions of the perfusate were collected during and after infusion. Kinetic parameters for myocardial accumulation and disposition of tocainide were indirectly determined from drug concentration/time course in the outflow perfusate. No stereoselectivity in myocardial accumulation was observed. A two compartment model with mean half-lives for distribution and elimination of 0.60 and 3.78 min, respectively, was fitted to the accumulation and disposition data. At steady-state, tocainide enantiomers were accumulated about three times in the myocardium relative to the perfusion liquid. PMID- 7794694 TI - Stereoselective binding of isradipine to human plasma proteins. AB - Isradipine (PN 200-110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl- and isopropylester, respectively). The binding of the (+)-(S)-isradipine and (-)-(R)-isradipine to isolated human serum albumin (HSA, 30 mumol/l) and alpha 1-acid glycoprotein (AAG, 10 mumol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06-20 mumol/l) using high-performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high-affinity binding sites on the AAG molecule (n(S) = 0.83 +/- 0.05, Ka(S) = (1.33 +/- 0.25) x 10(6) l/mol, n(R) = 0.85 +/- 0.07, Ka(R) = (1.17 +/- 0.44) x 10(7) l/mol). The (R)-enantiomer also exhibited an interaction with the secondary low-affinity binding sites (n'Ka'(R) = (2.66 +/- 0.65) x 10(4) l/mol). In contrast, the pharmacologically more potent (+)-(S)-enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 +/- 0.07, Ka(S) = (1.76 +/- 0.26) x 10(5) l/mol, nKa(R) = (3.62 +/- 0.06) x 10(4) l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10-80 ng/ml) at 37 degrees C was devoid of stereoselectivity. PMID- 7794695 TI - Chiral aspects of the metabolism of ethosuximide. AB - Ethosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The urinary metabolites of ethosuximide (following i.p. administration of the racemate or individual enantiomers to rats) have been studied using chiral gas chromatography (GC) and gas chromatography-mass spectroscopy (GCMS). The metabolites identified were unchanged ethosuximide enantiomers, all four stereoisomers of 2-(1 hydroxyethyl)-2-methylsuccinimide, and a single stereoisomer of 2-ethyl-3-hydroxy 2-methylsuccinimide [derived from (R)-ethosuximide]. Preliminary quantitative studies indicate a degree of stereoselectivity in the fate of ethosuximide since the ratio of (R)- to (S)-ethosuximide in the urine was found to be 0.77:1 (0-24 h sample), 0.64:1 (24-48 h sample), and 0.83:1 (48-72 h sample). This would suggest that the (R)-isomer is preferentially metabolised. Results obtained following the administration of individual enantiomers of ethosuximide indicate that the 2-(1 hydroxyethyl)-2-methylsuccinimide diastereoisomers derived from (R)-ethosuximide are produced in approximately equal proportions [ratio 1.05:1 (0-24 h sample), 1.10:1 (24-48 h sample)], whilst those from (S)-ethosuximide are produced in unequal proportions [ratio 1.65:1 (0-24 h sample), 1.74:1 (24-48 h sample)]. PMID- 7794696 TI - Planning a public health surveillance system. PMID- 7794697 TI - International Classification of Diseases, Tenth Revision. PMID- 7794698 TI - I Pan American Conference of Public Health Education and XVI Conference of the Latin American and Caribbean Association of Public Health Education (ALAESP). PMID- 7794699 TI - Nizatidine treatment of gastro-oesophageal reflux disease. PMID- 7794700 TI - Nizatidine versus placebo in gastro-oesophageal reflux disease: a 6-week, multicentre, randomised, double-blind comparison. Nizatidine Gastroesophageal Reflux Disease Study Group. AB - In a randomised, multicentre trial, nizatidine 150 mg or 300 mg or placebo was administered twice daily for 6 weeks to 515 patients with gastro-oesophageal reflux disease (GORD). Antacid tablets were taken as needed for pain. Significantly superior rates of endoscopically proven complete healing (normal appearing mucosa) versus placebo occurred after 3 weeks with nizatidine 150 mg and after 6 weeks with nizatidine 300 mg. Six-week healing rates were 38.5% for nizatidine 300 mg, 41.1% for nizatidine 150 mg, and 25.8% for placebo. The nizatidine 150 mg treatment group had significantly greater improvement in daytime and nighttime heartburn severity after 1 day of therapy versus placebo. Twice-daily administration of nizatidine 150 mg or 300 mg provides prompt relief from the major symptom of GORD, heartburn, and complete healing of oesophagitis is seen in many patients. PMID- 7794701 TI - Nizatidine versus placebo in gastro-oesophageal reflux disease: a 12-week, multicentre, randomised, double-blind study. AB - Two doses of nizatidine (150 mg twice daily and 300 mg at bedtime), an H2 receptor antagonist, were compared with placebo in a 12-week, multicentre, randomised, double-blind, parallel study in 466 patients with endoscopically documented gastro-oesophageal reflux disease. Antacid tablets were given concomitantly as needed for pain. Compared with placebo, nizatidine 150 mg twice daily was highly effective in rapidly reducing the severity of heartburn, regardless of oesophagitis severity at entry. Significantly greater complete mucosal healing of oesophagitis occurred after 6 weeks of therapy with nizatidine 150 mg bid (vs nizatidine 300 mg at bedtime or placebo) only in patients with erosive oesophagitis [16/68 (24%) vs 8/65 (12%)] and erosive and ulcerative oesophagitis combined [21/99 (21%) vs 10/94 (11%)]. At week 12, healing with nizatidine 150 mg bid was also significantly greater than placebo in erosive [19/68 (28%) vs 9/65 (14%)], ulcerative [10/31 (32%) vs 3/29 (10%)], and erosive and ulcerative oesophagitis combined [29/99 (29%) vs 12/94 (13%)]. These results show that twice-daily therapy with nizatidine 150 mg is very effective at relieving heartburn, and can also heal erosive and ulcerative oesophagitis. Nizatidine 300 mg at bedtime was not effective at healing oesophagitis, compared with placebo. PMID- 7794703 TI - Do patients who are treated with calcitriol for renal osteodystrophy also need vitamin D3 therapy? PMID- 7794702 TI - Urinary infection, reflux and renal scarring in females continuously followed for 13-38 years. AB - This study describes the pattern of urinary tract infections (UTI) in 87 females prospectively followed for a median of 23 years from their first recognized symptomatic infection in childhood. At 16 years of age they were selected for follow-up into adulthood because of renal scarring (reflux nephropathy) in 45 and recurrent UTI in 42. The attack rate (number of urinary tract infections per individual per observation year) was highest during the 1st year of life (1.9), with a gradual decrease to the lowest rate (0.2) at age 11-15 years. A moderately increased attack rate (0.4), was seen in the late teens, extending through to the mid twenties. The proportion of infections having a pyelonephritic character decreased with age and number of infection episodes, but not in females with severe renal scarring. Pyelonephritic infections were correlated with vesicoureteric reflux, and renal scarring to low age at the index infection, total number of pyelonephritic episodes and reflux. Females with renal scarring continued to have a high proportion of pyelonephritic recurrences after 10 years of age, implying that they risk progressive renal disease and should be closely followed into adulthood. PMID- 7794704 TI - Steroid-resistant, cyclosporine-responsive, relapsing nephrotic syndrome. AB - Eighteen children with steroid-resistant nephrotic syndrome received cyclosporine A (CsA), including 7 patients with minimal change disease, 4 with focal segmental glomerulosclerosis and 7 with mesangial hypercellurarity. Doses were adjusted to maintain whole blood trough levels at 80-200 ng/ml and ranged from 5 to 10 mg/kg (mean 7 mg/kg). Fourteen patients responded after 2 months of therapy with either a complete or partial remission, and received a total of 12 months of CsA with low-dose corticosteroids. Remission rates were similar among the three histological types, although complete remissions occurred more commonly in minimal change disease, while the other two histological types tended to have partial responses. Serum creatinine values ranged from 0.3 to 1.2 mg/dl at the start of treatment and were stable in 17 of 18 patients during CsA therapy. CsA was discontinued after 12 months in 11 responders. Relapses were a significant problem. Nine patients had 16 relapses, all occurring within 6 months after discontinuing CsA; 13 of 16 relapses responded to CsA and corticosteroids. Five children had multiple relapses. Three patients who initially responded to treatment had CsA-resistant relapses. There were no differences among the histological types with respect to the occurrence of relapses or response to CsA after relapsing. Four patients developed chronic renal failure, including 2 of 4 who failed initial therapy and 2 of 3 who developed CsA-resistant relapses. In conclusion, initial therapy with CsA was effective in resolving nephrotic syndrome in steroid-resistant patients. However, CsA dependency, frequent relapses and the development of chronic renal failure presented significant problems. PMID- 7794705 TI - Non-nephrotic children with membranoproliferative glomerulonephritis: are steroids indicated? AB - Alternate-day steroids are currently recommended to treat children with membranoproliferative glomerulonephritis (MPGN). This recommendation is based largely on uncontrolled studies demonstrating improved renal survival with steroid therapy. We reviewed the outcome of 39 children who presented with MPGN between 1968 and 1990; 27 children were treated with steroids and 12 children received no drug therapy. Life-table analysis comparing renal survival of treated versus untreated children demonstrated no difference by log rank analysis. Treated and untreated groups were compared on the basis of nine features at presentation: age, sex, type of MPGN, presence and type of hematuria, hypocomplementemia renal insufficiency, hypertension, and nephrosis. Treated children were likely to be female (P < 0.01) and nephrotic (P < 0.02). Actuarial survival analyses were performed comparing the nine features with renal survival through 10 years of follow-up. Normotensive (P < 0.025) and non-nephrotic (P < 0.05) children had improved renal survival. The 11 non-nephrotic children demonstrated 100% long-term renal survival, including 7 who received no steroid therapy. At last follow-up, all non-nephrotic children had normal renal function, serum albumin levels > 3 g/dl, and were normotensive. These data suggest that non nephrotic children with MPGN may forego steroid treatment without compromising long-term renal function. The current common practice of treating all children with MPGN with steroids should be re-examined. PMID- 7794706 TI - Localization of extracellular matrix components in congenital nephrotic syndromes. AB - While renal tissue from one fetus and a newborn with congenital nephrotic syndrome, Finnish type (FCNS), showed a normal basement membrane (BM) localization and composition, in another type of congenital nephrotic syndrome, diffuse mesangial sclerosis (DMS), most glomeruli demonstrated a completely disorganized matrix. In the latter, hyalinized glomerular segments were composed of irregular deposits of interstitial collagens I, III, V, and extensive deposits of heparin sulphate proteoglycan (HSPG), while collagen IV and laminin were completely absent in those areas. Apart from these sclerosed glomerular areas, normal capillarly loops revealed a matrix composition that was comparable to normal glomeruli. The additional immunolocalization of various extracellular matrix components during the development of normal human glomeruli revealed some significant age-dependent changes both in the localization of interstitial collagens and BM components: interstitial collagens I and III disappeared after the first S-shaped indentations appeared, while the interstitial collagen V remained along the glomerular BM and within the mesangium. The BM components showed no significant qualitative changes, but quantitative changes, with a post natal relative decrease in the collagen IV and laminin content when compared with the level of BM-associated HSPG. Our results provide circumstantial evidence that the composition of the extracellular matrix (and in particular of the BM) shows age-dependent quantitative changes which may be associated with functional adaptation processes of the developing kidney. The observed matrix composition in the two different congenital nephrotic syndromes suggests various pathomechanisms which may be located either in the molecular structure of the negatively charged molecules (e.g. abnormal sulphatation of HSPG in FCNS) or in the dysregulated synthesis of various matrix components (DMS). PMID- 7794708 TI - What, if any, is the appropriate neurological work-up for a child with autosomal dominant polycystic kidney disease and a family history of intra-cranial aneurysm? PMID- 7794707 TI - Glomerular hyperfiltration increases the risk of developing microalbuminuria in diabetic children. AB - An elevated glomerular filtration rate (GFR) is frequently detectable in type 1 diabetic children and adolescents and in those without any other evidence of incipient diabetic nephropathy. In 1982 we detected 23 patients with hyperfiltration (GFR > 140 ml/min per 1.73 m2), aged 9-15 years, with diabetes for longer than 4 years; 23 age- and sex-matched patients with diabetes of a similar duration and without hyperfiltration served as controls. Both groups were followed until March 1992, by assessing GFR every 12 months, albumin excretion rate every 6 months, blood pressure and glycated haemoglobin (HbA1) every 3 months. Dietary protein intake was similar in patients with hyperfiltration and in controls. No other drug except insulin was used throughout the study. The insulin regimen was similar in the two groups. There was no significant difference between the two groups regarding albumin excretion, blood pressure and HbA1 at the beginning of the study. Of the 23 patients with hyperfiltration, 7 developed persistent microalbuminuria (defined as an overnight albumin excretion rate > 30 micrograms/min per 1.73 m2 on at least 5 consecutive measurements); 2 of these patients had overt proteinuria. Only 1 of the diabetics with normal GFR developed persistent microalbuminuria. The positive predictive value for microalbuminuria of an initial GFR > 140 ml/min per 1.73 m2 was 63%; the negative predictive value of an initial GFR < 140 ml/min per 1.73 m2 was 94%. The increase of albumin excretion rate into the microalbuminuric range precedes the elevation of both systolic and diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794709 TI - Mineral excretion following furosemide compared with bumetanide therapy in premature infants. AB - Mineral excretion following single doses of furosemide were compared with bumetanide in a random cross-over trial in 17 premature infants. The mean birthweight and gestational age were 889 +/- 85 g and 27 +/- 2 weeks. Following furosemide therapy, significantly higher chloride losses and urine volumes were noted in the first 8-h period compared with the second or third 8-h periods. Following bumetanide therapy, sodium, calcium, and chloride losses and urine volumes were significantly higher in the first 8 h compared with the second or third 8-h periods. Hourly sodium and chloride losses were significantly lower following bumetanide than furosemide during the first two 8-h periods. During the final 8-h period sodium, potassium, chloride, and calcium losses were significantly lower following bumetanide than following furosemide. Sodium loss per urine volume was lower with bumetanide than furosemide but calcium loss tended to be higher. Hence, bumetanide does not appear to be a calcium-sparing diuretic following single-dose therapy. PMID- 7794710 TI - Renal function in premature infants during aminoglycoside therapy. AB - The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P < 0.05 and P < 0.01, respectively) and an increase in FENa and UCa/UCr in group C (P < 0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant. PMID- 7794711 TI - Ambulatory blood pressure monitoring in paediatric patients treated by regular haemodialysis and peritoneal dialysis. AB - Ambulatory blood pressure monitoring (ABPM) has been shown to be more representative of blood pressure (BP) levels than casual BP measurements in adult patients treated by haemodialysis (HD). In this study we compared ABPM using the oscillometric SpaceLabs 90207 monitor with casual BP measurements in 35 paediatric patients [17 treated by peritoneal dialysis (PD) and 18 by HD]. Heart rate and plasma concentrations of atrial natriuretic peptide were also measured. No correlations were found between ABPM and causal BP measurements, except for systolic day-time BP in PD patients (r = 0.63). Seventy percent of PD and 33% of HD patients were regarded as hypertensive when evaluated by ABPM, while casual BP measurements demonstrated hypertension in 47% (P < 0.05) of PD patients and in 44% (NS) of HD patients. One-third of patients were reclassified by ABPM either from normotensive to hypertensive (7/19) or from hypertensive to normotensive (5/16). BP assessed by ABPM was higher in PD than in HD patients. The physiological decline of BP at night was significant and more pronounced in PD than in HD patients. In HD patients day-time BP did not differ between the 1st and the 2nd interdialytic day, but increased in the night hours before the following dialysis session. A positive correlation was found between day-time BP and pre-dialysis plasma atrial natriuretic peptide in both treatment groups. In conclusion this study demonstrates that casual BP recordings are not representative of average BP in dialysed paediatric patients. ABPM is useful in the diagnosis and treatment of hypertension in children with end-stage renal disease. PMID- 7794712 TI - Nephrocalcinosis in X-linked hypophosphatemia: effect of treatment versus disease. AB - While the literature has suggested that vitamin D and phosphate therapy benefits children, and possibly adults, with X-linked hypophosphatemia (XLH), there have been increasing reports of nephrocalcinosis by renal ultrasound examination in treated patients. Although it has been assumed that nephrocalcinosis is the result of treatment, there has been no systematic comparison of treated and untreated XLH patients with long-term follow-up. Therefore, we studied 10 adults and 4 children by renal ultrasound examination with no history of medical therapy and 10 adults and 8 children with a history of medical therapy. None of the untreated patients had nephrocalcinosis; 5 treated adults and 5 treated children had nephrocalcinosis. In 3 of 4 treated children, serial renal ultrasounds did not show progression of the nephrocalcinosis. One patient progressed from baseline to year 1 only. Comparisons of means between treated patients without and with nephrocalcinosis showed statistically significant differences for urine calcium/creatinine ratios and urine phosphorus/creatinine ratios, differences not seen between untreated patients and treated patients without nephrocalcinosis. Phosphate dose, but not vitamin D dose, was statistically significantly different between the two treated groups. Our studies point to a convincing role for the association between nephrocalcinosis, as diagnosed by renal ultrasound examination, and medical therapy. PMID- 7794713 TI - Effects of growth hormone on kidney function in pediatric transplant recipients. AB - Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6 +/- 3.4 years) received rhGH daily (0.04-0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20 +/- 8 months) of rhGH treatment. Their mean serum creatinine level was 1.3 +/- 0.7 mg/dl 12 months before, and increased to 3.4 +/- 4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P = 0.06). Their mean calculated glomerular filtration rate was 58 +/- 20 ml/min per 1.73 m2 12 months before, and decreased to 38 +/- 21 ml/min per 1.73 m2 after 12 months of rhGH treatment, but did not achieve statistical significance (P = 0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant. PMID- 7794714 TI - Nephroblastoma and end-stage renal failure with bilateral cystic kidneys. AB - A child of 10 years 5 months presenting with chronic renal failure had bilateral cystic kidneys. Biopsy of a right lower-pole solid mass revealed nephroblastoma. At bilateral nephrectomy, both kidneys were both replaced by variable-sized cysts with a unifocal nephroblastoma on the right. Renal failure with nephroblastoma is uncommon and is usually either a manifestation of the Drash syndrome or a complication of chemotherapy. The need to assess both kidneys in a child with any other renal abnormality in addition to a renal mass should always be considered. PMID- 7794715 TI - IgG subclass levels in pediatric patients on chronic peritoneal dialysis. AB - Patients maintained on chronic peritoneal dialysis (CPD) have been reported to have a variety of abnormalities of humoral immunity, including hypogammaglobulinemia, altered response to vaccination, and selective absence of IgG2. We measured serum immunoglobulin and IgG subclass levels in 22 pediatric CPD patients followed at our institution; 8 patients had low total IgG; 4 of these had low levels of IgG2 and 3 also had low IgG1, but IgG2 levels were detected in all patients. Thus, many pediatric CPD patients may have low IgG, and some may have low IgG1 and IgG2 as a reflection of low total IgG. However, we did not demonstrate a selective absence of IgG2 in these patients. PMID- 7794717 TI - Tubulointerstitial nephritis and uveitis: an immunological disorder? AB - A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response. PMID- 7794716 TI - Paediatric renal transplantation non-compliance. AB - The aim of this study was to quantify and where possible objectively confirm the magnitude of non-compliance (NC) in our paediatric renal transplant recipients. A total of 94 paediatric transplants were performed between 1984 and 1989; 17 were excluded due to graft loss (2), death (3), oxalosis (2) and transfer to the adult unit (10). NC was assessed as missed clinic visits plus medication shortages or actual admission of NC. NC was found in 22% (17/77) of transplanted patients. NC showed no correlation with parental marital status, sex, distance lived from the hospital, pre-emptive transplant status or total lymphoid irradiation. Most NC was peripubertal with a smaller NC in the late teenager group. Social class correlated positively with NC; 82.3% of NC was from social classes III and IV, who formed 52.4% of the patients. NC in social class II (3/26) was significantly different from social class IV (12/24) (P = 0.01); 91% of black patients with NC were from social class IV. Race, corrected for social class, failed to reach significance (P > 0.05). Confirmation of compliance was sought from retrospective cyclosporin A (CsA) trough levels (twice daily dosage). Concomitant phenytoin therapy and CsA given as a daily dosage were excluded as significant confounding variables. The CsA dosage was not significantly different between the compliant (C) and patients with NC. Patients with NC were 8 times more likely to have a CsA level < 10 ng/ml (P = 0.0026) than C patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794718 TI - Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring. AB - Recently, a new oral microemulsion formulation of cyclosporin A (CsA)--Neoral (Sandoz, Basle, Switzerland)--with a higher bioavailability has become available. Ten stable paediatric renal transplant recipients with excessive variations in CsA trough levels with the original Sandimmun (Sandoz, Basle, Switzerland) preparation were switched to Neoral on a 1:1 basis. Pharmacokinetic studies revealed impaired absorption of Sandimmun in six patients. Compared with equal doses of Sandimmun, the 8-h area under the concentration-time curve increased from 1,422 to 2,657 ng x h/ml and the peak concentration rose from 319 to 824 ng/ml (P < 0.01). In six patients with Sandimmun malabsorption, conversion on a 1:1 basis led to a reduction in creatinine clearance which was reversible after dose reduction by 9%-25%. With trough levels at the lower end of the present target range, creatinine clearance stabilised around pre-conversion values. PMID- 7794719 TI - Balloon dilation of inferior vena cava stenosis causing hemodialysis graft failure. AB - Inferior vena cava stenosis developed after an unsuccessful renal transplant in a 3-year-old child. Resulting venous outflow obstruction consequently prevented construction of a functional hemodialysis arteriovenous shunt at the femoral area. Transluminal balloon angioplasty of the stenosis completely eliminated the obstruction and allowed creation of the shunt. PMID- 7794720 TI - Renal biopsy in children: indications, technique and efficacy in 119 consecutive cases. AB - Consecutive renal biopsies were performed on native kidneys in 109 children and adolescents, aged 0.1-19.8 (mean 9.9) years (119 biopsies). Bleeding diatheses were excluded or treated pre-operatively with intravenous desmopressin acetate. Biopsies were performed by a radiologist under ultrasound imaging, using an automated spring-loaded device allowing selection of the length of the needle movement and score size. Diagnostically adequate tissue was retrieved in 118 of 119 (99.2%) biopsy procedures; 24-h post-biopsy ultrasonography disclosed a small haematoma of the biopsied kidney in 26% of the cases. No correlation was seen between the occurrence of haematoma and (treated) prolonged bleeding time or a decrease in the haemoglobin level. No major complications occurred. Newly developed macroscopic haematuria was reported by 7% and micturition pain by 7% of patients. Painful body movements were reported by 37%. We conclude that the use of ultrasound imaging and an automated gunshot technique is a safe and efficient method for performing renal biopsies in paediatric patients. PMID- 7794721 TI - Anti-neutrophil cytoplasmic antibody associated glomerulonephritis in a patient with Down's syndrome. AB - A 9-year-old boy with Down's syndrome developed a glomerulonephritis associated with crescents and anti-neutrophil cytoplasmic antibodies (ANCA). The patient also had type 1 diabetes mellitus, chronic lymphocytic thyroiditis, and bronchial asthma. Prednisone therapy resulted in an improvement in renal function and a reduction in ANCA titers. PMID- 7794722 TI - Tumor lysis syndrome: pathogenesis and management. AB - Tumor lysis syndrome refers to the metabolic disturbances (hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia) associated with lymphoproliferative malignancies which occur secondary to cell lysis. In some patients, tumor lysis results in acute renal failure. The nature and severity of the metabolic alterations are variable and may be influenced by the timing and intensity of chemotherapy, the magnitude of cell lysis, and the general condition of the patient with respect to hydration and glomerular filtration rate. Not only do hyperuricemia and hyperphosphatemia result from tumor lysis syndrome, they also contribute to oliguric acute renal failure in patients with tumor lysis. The pathogenesis of tumor lysis syndrome and current therapeutic strategies are discussed. PMID- 7794723 TI - The intravenous urogram in the detection and evaluation of renal damage following urinary tract infection. AB - Intravenous urography (IVU) still provides the most comprehensive structural assessment of the urinary tract. In particular, the radiological renal appearances approximate closely to the morphology of the renal scarring of reflux nephropathy or chronic atrophic pyelonephritis. It also provides reproducible renal measurements for follow-up assessment of renal growth and scarring. It is now less often used for first-line investigation of the acute urinary tract infection (UTI) because the swelling accompanying acute renal involvement is less easily recognised than the areas of defective function demonstrated on 99mtechnetium-dimercaptosuccinic acid (DMSA) studies. Also IVU contributes a higher radiation dose when calculated for full IVU (dependent on the number of films exposed) and there is a slight risk of side effects from injected contrast media, reduced by using non-ionic compounds. Because of its value in confirming such a serious diagnosis as renal scarring, suspected on ultrasonography or DMSA scintigraphy, modification of the technique of IVU with adequate preparation and the use of a reduced number of films, or single films localised to the renal areas, should be considered. Expertise in the interpretation of IVU must also be maintained because of the ancillary information regarding bowel and bladder function, the spine and evidence of stones, pertinent to the management of children with UTI and renal scarring. IVU and DMSA study remain complementary investigations. PMID- 7794724 TI - Update on dimercaptosuccinic acid renal scanning in children with urinary tract infection. AB - The dimercaptosuccinic acid (DMSA) renal scan is a method for assessing kidney function. Indications for DMSA scanning in children with urinary tract infection (UTI), as well as timing, have changed. Pitfalls in interpreting DMSA scans include: (1) acute pyelonephritis (APN), (2) tubular dysfunction, (3) hypertension, (4) use of captopril in patients with renovascular hypertension and (5) duplex kidneys. Interpretation of DMSA scans in children with UTI vary according to timing and clinical setting. During the course of a febrile UTI a DMSA scan may reveal a normal kidney, APN or a non-functioning, small and/or ectopic kidney. In the absence of UTI (up to 6 months) in children with vesicoureteric reflux a DMSA scan may indicate a normal kidney, renal scarring (reflux nephropathy), occult duplex kidney and allows the progression of scarring and hypertrophy of normal areas of the kidney to be followed anatomically. The DMSA renal scan in now the most reliable test for the diagnosis of APN. The transient abnormalities due to APN can occur in normal or scarred kidneys. Lesions due to reflux nephropathy (defined as a defect in the renal outline or contraction of the whole kidney) are permanent. Intravenous urography reveals renal abnormalities later than the DMSA scan. If abnormalities are seen on a DMSA scan performed during the course of APN it is impossible to predict the outcome: they can progress to permanent scarring or heal completely. An abnormal DMSA scan during a febrile UTI allows the identification of children at risk of developing renal scars. These children should be carefully investigated, maintained on long term quimioprophylaxis and followed. PMID- 7794726 TI - Clinical quiz. Renal amyloidosis. PMID- 7794727 TI - Clinical quiz. Cerebral venous thrombosis. PMID- 7794728 TI - Reversible encephalopathy after intravenous ciprofloxacin therapy. PMID- 7794725 TI - Nitric oxide and endothelin in pathophysiological settings. AB - The role of the endothelium is now known to encompass the generation of many potent cytokines which impact endothelial cells, adjacent tissue such as smooth muscle cells, and distant sites in an autocrine, paracrine, and endocrine manner, respectively. This review addresses two of these cytokines, nitric oxide and endothelin, and describes how each effects the functions of endothelial cells, including regulation of platelet aggregation and coagulation, regulation of vasomotor tone, modulation of inflammation, and the regulation of cellular proliferation. The emphasis is on the increasingly recognized importance of the autocrine and paracrine mechanisms by which nitric oxide and endothelin act. In particular, autoinduction of endothelin is proposed as a central mechanism underlying endothelin's renowned effects. Additionally, specific nitric oxide/endothelin interactions are discussed by which each cytokine modulates the production and actions of the other. The net effect observed in a variety of physiological and pathophysiological settings, therefore, reflects a balance of these opposing functions. PMID- 7794729 TI - Do children with diffuse mesangial sclerosis in association with mutations of the Wilm's tumour suppressor gene (WT1) require bilateral nephrectomy? PMID- 7794731 TI - Approval of cysteamine for patients with cystinosis. PMID- 7794730 TI - Renal anomalies in Down syndrome. PMID- 7794732 TI - Computed tomography or intravenous urography in the evaluation of renal damage in children with urinary tract infection? PMID- 7794734 TI - Expanded programme on immunization (EPI). Progress towards the global elimination of neonatal tetanus, 1989-1993. PMID- 7794733 TI - Computed tomography or intravenous urography for renal damage in childhood urinary infection? PMID- 7794735 TI - Cerebrospinal meningitis. PMID- 7794736 TI - Diarrhoeal diseases in Bali. PMID- 7794737 TI - A man of standards. Interview by Graham Scott. PMID- 7794738 TI - Community care. Temporary address, permanent care. PMID- 7794740 TI - Male nurses: losing their job advantage? AB - Though the overall population of nurses remains at the same level, the number of male nurses is on the rise. With male nurses traditionally being an advantaged minority, this may increase competition for jobs. PMID- 7794739 TI - The role of the nurse: extended or expanded? AB - The subject of role extension has been much debated, particularly in recent years as a result of changing healthcare policies, growing demands by nurses and the public, and arguments about the very nature of nursing itself. The recent media furore over the theatre sister who performed an appendectomy is but one example. This article will take account of recent trends and look at the different concepts of role extension and role expansion. How nursing can best adapt these roles to meet patients' needs will also be considered. PMID- 7794741 TI - Blood transfusion (continuing education credit). PMID- 7794742 TI - Grief reactions and learning disabilities. AB - Although the past two decades have seen an unprecedented interest among professionals in issues related to death, bereavement and grief, there is still a great deal of ignorance about grief among people with learning disabilities. Such ignorance can affect the overall care of bereaved people and may cause professionals to interpret normal grief reactions incorrectly (1). PMID- 7794743 TI - Gender: know your place. PMID- 7794744 TI - Disabled rights: free wheeling. PMID- 7794745 TI - AIDS-related lymphomas: from pathogenesis to pathology. PMID- 7794746 TI - Trisomy 11: an association with stem/progenitor cell immunophenotype. AB - The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis. PMID- 7794747 TI - A phase I/II trial of recombinant human interleukin-6 in patients with aplastic anaemia. AB - In a phase I/II study, 11 patients with marrow failure (10 with acquired aplastic anaemia and one with pancytopenic Fanconi anaemia) were treated with recombinant human interleukin-6 (rhIL-6) to assess the safety and tolerability of rhIL-6 and its effects on peripheral blood counts, bleeding complications and transfusion requirements. All patients with acquired aplastic anaemia were refractory to immunosuppressive treatment or had relapsed after immunosuppressive therapy and were not bone marrow transplantation candidates. Recombinant hIL-6 was to be given as a once-daily subcutaneous injection for 28 d at doses ranging from 0.5 to 5.0 micrograms/kg. After an observation period of 2 weeks, five patients received a second treatment course of 28 d. Only one patient had a sustained increase in platelet count from 18,000 to 72,000/microliters. Bleeding occurred in four patients and caused premature discontinuation of rhIL-6 therapy in three patients. A deterioration of pre-existing anaemia was observed in nine patients. No significant changes of leucocyte counts were observed during the first cycle. During the second cycle the peripheral blood monocyte counts decreased significantly. No significant changes in bone marrow cellularity were observed. Recombinant hIL-6 induced a dose-dependent increase in acute-phase reactants in all patients. Other adverse events included fever, headache, arthralgia, tachycardia and hypertension. In conclusion, rhIL-6 given alone at low doses does not increase platelet counts in the majority of patients with aplastic anaemia and can precipitate a sudden worsening of pre-existing anaemia and thrombocytopenia. This study was discontinued prematurely on account of the toxicity of rhIL-6 seen in patients with aplastic anaemia. PMID- 7794748 TI - Flow cytometric analysis of homologous restriction factor 20KD (HRF20) expression on progeny cells during differentiation from haemopoietic progenitors in paroxysmal nocturnal haemoglobinuria. AB - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder with a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins. Homologous restriction factor 20KD (HRF20, CD59) is a GPI-anchored and major complement regulatory protein which plays a key role in the haemolytic mechanism of PNH. We examined the differentiation stage at which the PNH abnormality occurs, by means of flow cytometric analysis of HRF20 expression. Non-phagocytic mononuclear marrow cells were labelled with anti-HRF20 monoclonal antibody and sorted into either HRF20-negative or -positive fractions. The sorted cells were cultured in methylcellulose and their progeny in the colonies or bursts were analysed for HRF20 expression. All colonies and bursts from HRF20-negative fractions remained negative, whereas those from HRF20-positive fractions were either positive or negative. The possibility of a sorting error was excluded, because the secondary colonies from the HRF20 positive primary colonies consisted of both positive and negative progeny. These results suggest that there are several stages during differentiation from early progenitors to mature cells, at which the PNH abnormality becomes manifest. PMID- 7794749 TI - Molecular analysis of the chromosomal breakpoint and fusion transcripts in the acute lymphoblastic SEM cell line with chromosomal translocation t(4;11). AB - The chromosomal breakpoint and fusion transcripts of the pre-B-leukaemia-derived SEM cell line carrying a reciprocal t(4;11)(q21;q23) translocation were analysed. The breakpoint from derivative chromosome der4 was cloned and sequenced. The crossover site was localized in intron 7 of the ALL-1 gene on chromosome 11q23 and in a large intron of the AF-4 (FEL) gene. RNA transcripts from both wild-type genes and both hybrid genes were detected by reverse transcriptase polymerase chain reaction (RT-PCR) assays. In addition, alternatively spliced mRNA species derived from the der4 chromosome were found. They were generated by using the exon 5' of the breakpoint on der4 as a common splice donor site and the 5' boundaries of exons 8 or 9 of the ALL-1 gene as alternative splice acceptor sites. The hypothesis is proposed that selective pressure operators to maintain the presence of both derivative chromosomes as important elements in the leukaemogenic process. PMID- 7794750 TI - Antenatal screening for fetal alloimmune thrombocytopenia: the results of a pilot study. AB - Feto-maternal incompatibility for the human platelet antigen HPA-1a is an important cause of severe fetal thrombocytopenia. The incidence is 1 in 1000-2000 pregnancies, which is more common than other conditions for which screening is presently carried out. Antenatal diagnosis and management are now available, but only for subsequent siblings following diagnosis of a previously affected infant. This study describes a pilot prospective screening programme for the antenatal detection of fetomaternal alloimmune thrombocytopenia (FMAIT) due to HPA-1a incompatibility. 3473 women were typed for HPA-1a using a method designed for large-scale typing. 71 women found to be HPA-1a negative were further tested for HLA-DR52a as a risk factor for alloimmunization. All women were monitored for the development of anti-HPA-1a throughout pregnancy and a cord full blood count was taken at delivery. Two affected pregnancies were found and treated: a singleton pregnancy was treated antenatally and a twin pregnancy after delivery. The study showed that screening for FMAIT could be established within the pre-existing antenatal red cell serology programme. It was concluded that screening should be based on platelet typing and offered regardless of parity. Further stratification, combining DR52a typing and HPA-1a antibody screening, although focusing on the group of women at greater risk, may not identify all affected pregnancies. Confirmation of the diagnosis and severity of FMAIT continues to depend on fetal blood sampling during pregnancy or cord blood samples after birth. PMID- 7794751 TI - The determination of spontaneous megakaryocyte colony formation is an unequivocal test for discrimination between essential thrombocythaemia and reactive thrombocytosis. AB - Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C). The culture medium which was used in the methylcellulose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU-Mk growth was recorded in all patients with ET but in none with RT or in C. BMs-CFU-Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr. Spontaneous bone marrow erythroid progenitors (BMsBFU-E) were also determined in these patients. BMsBFU-E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU E. We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU-Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies. In addition, we present evidence that in 10 patients BMsCFU-Mk and/or BMsBFU-E growth in the test persisted after long-lasting haematological remission. PMID- 7794752 TI - Bacterial infection-associated improvement of platelet counts in two patients with chronic and unresponsive idiopathic thrombocytopenic purpura with normal platelet survival studies. AB - Approximately 20% of adult patients with idiopathic thrombocytopenic purpura (ITP) do not respond to splenectomy and require alternative therapies to achieve a clinically safe platelet count. A small percentage of these patients have very refractory disease and are either unresponsive or poorly responsive to almost any therapy. In this report we describe two patients with chronic and unresponsive ITP with normal platelet survivals. Neither patient had responded to a large variety of treatments including corticosteroids, splenectomy, IVIgG, anti-D, chemotherapy, and ascorbic acid. However, both had a rapid, but short-lived, rise in their platelet count following a bacterial infection. One patient had a rise in platelet count for 6 months following the acute episode of bacteraemia. The second patient had a shorter response of 1 week. It is possible that these two patients represent a subset of patients with ITP who may benefit from cytokine therapy. PMID- 7794753 TI - Direct evidence for dissociated megakaryocytic chimaerism in a Wiskott-Aldrich patient successfully allografted. AB - We report a Wiskott-Aldrich patient who underwent allogeneic bone marrow transplantation from his HLA-identical sister at the age of 25. Conditioning regimen consisted of cyclophosphamide (180 mg/kg) and thoraco-abdominal irradiation (6 Grays). Cytogenetic follow-up revealed rapid and complete lymphoid chimaerism, but prolonged mixed bone marrow chimaerism. Correlative interphase cytogenetics performed on bone marrow smears using dual-colour fluorescence in situ hybridization with X and Y specific probes showed that the proportion of donor cells was significantly higher within megakaryocytes than in other lineages. This patient therefore presented with dissociated lineage engraftment, which is not exceptional in congenital diseases and aplastic anaemia, but has not previously been described in Wiskott-Aldrich syndrome. Bone marrow transplantation was successful despite this delayed engraftment which ensured adequate production in the involved cell lines. PMID- 7794754 TI - Sustained increase in haemoglobin and RBC following long-term administration of recombinant human erythropoietin to patients with homozygous beta-thalassaemia. AB - Recombinant human erythropoietin (rHuEPO) was given subcutaneously three times per week in an escalating dose from 500 u/kg to 950 u/kg together with ferrous fumarate 305 mg and folic acid 5 mg/d, to 10 patients from four unrelated Arab families with homozygous beta-thalassaemia. Six splenectomized patients showed a mean (+/- standard error) increase in haemoglobin from 7.1 +/- 0.1 to 9.3 +/- 0.1 g/dl (P = 0.0001), in RBC from 4.0 to 5.0 x 10(12)/l (P = 0.0001) and in nucleated RBC from 32 +/- 7 x 10(10)/l to 82 +/- 6 x 10(10)/l while receiving 750 u/kg three times per week which persisted for 4-11 months. In two patients there was no need for further blood transfusions. In three out of four unsplenectomized patients there were no changes in Hb and RBC despite dose escalation. There were no significant changes in MVC, MCH and reticulocyte count, serum bilirubin, LDH, malonyldialdehyde (MDA) and vitamin E levels. After 13 weeks of rHuEPO there was a mean increase in the percentage of F cells from 31 +/- 10% to 86 +/- 6% (P < 0.003) in three splenectomized patients and in one unsplenectomized patient from 56.4% to 80% without changes in the levels of Hb F. Globin chain synthesis ratios did not change in four responding patients. Mean serum iron and transferrin saturation index did not change, whereas mean serum ferritin increased from 299 +/- 45 micrograms/l to 480 +/- 20 micrograms/l (P < 0.001). In seven responding patients an accelerated linear growth was indicated by positive changes in height standard deviation score for chronological age. Side-effects were minimal throughout the treatment period. PMID- 7794756 TI - Rearrangement of the immunoglobulin heavy chain gene in juvenile chronic myeloid leukaemia. AB - Five patients with clinical and laboratory features typical for juvenile chronic myeloid leukaemia (JCML) are presented. Rearrangement of the j joining region of the immunoglobulin heavy chain (Jh) was demonstrated in three children out of five analysed. As no Vh to DhJh nor kappa light chain rearrangements were demonstrated, it is reasonable to speculate that the transforming event of the stem cell happened at the stage when Dh to Jh rearrangement took place. As the monocytic lineage is prominent in JCML, it is suggested that the transforming event happens in a unique stem cell with intermediate differentiation towards the myelomonocytic as well as the B-lymphatic lineage. This stem cell, which is present at a certain stage of embryogenesis, disappears later. Such an early 'hybrid' cell is sometimes involved in leukaemias of early infancy, and may be the transformed cell in some cases of infantile leukaemia. PMID- 7794755 TI - Philadelphia chromosome-negative chronic myeloid leukaemia: a report of 14 new cases. AB - The Philadelphia chromosome (Ph) is the cytogenetic hallmark of chronic myeloid leukaemia (CML) and is used to confirm the diagnosis of CML based on clinical and morphological criteria. We investigated 14 patients with features of CML but without detectable Ph chromosome. In seven patients, referred to as BCR+, M bcr/abl rearrangement was detected by polymerase chain reaction (PCR). The seven remaining patients did not have M-bcr/abl rearrangement and are described as BCR . BCR- patients were younger, had lower white blood cell counts (WBC) and lower basophilia. Four BCR- and four BCR+ patients underwent blastic transformation (BT). Response to therapy was fairly similar in both populations. According to French-American-British (FAB) Cooperative Leukaemia Group guidelines, all BCR- patients were classified as having classic form CML or 'chronic granulocytic leukaemia' (CGL) when based only on morphological data. This study further confirms the existence of true CML cases without Ph chromosome or M-bcr/abl rearrangement and shows that this entity differs only slightly from classic form Ph+ CML. The Ph-BCR- subgroup raises two problems. First, the differential diagnosis with atypical CML or CMML, based on morphological data, and secondly, the therapeutic follow-up in the absence of a specific marker. In contrast, the residual disease of Ph-BCR- patients can be monitored by PCR. More advanced molecular and biochemical techniques will be required to understand which molecular mechanisms underlie Ph-BCR- CML, resulting in phenotypes sometimes indistinguishable from Ph+ CML. PMID- 7794757 TI - Abnormal TCR V beta repertoire in patients with chronic myeloid leukaemia. AB - We have used 25 sets of oligonucleotide primers specific for the 24 known major human T-cell receptor (TCR) V beta families in polymerase chain reactions to analyse the T-cell repertoire of the peripheral blood in seven patients with chronic myeloid leukaemia (CML). In contrast to normal healthy individuals, all seven patients exhibited variable degrees of TCR V beta-specific T-cell deletion, ranging from two to eight of the 24 major families. T cells bearing V beta 17 and 8 were most commonly deleted. These results suggest a superantigen effect associated with CML. The patterns of deletion did not appear to correlate with either of the two bcr-abl transcripts. The reason and aetiological agent responsible for the T-cell deletion remain speculative. Further work is ongoing to characterize this phenomenon in animal models and patients with CML. PMID- 7794759 TI - Low incidence of MDR1 expression in acute promyelocytic leukaemia. AB - The MDR1 gene product, P-glycoprotein, functions as a transmembrane efflux pump for certain cytotoxic agents including anthracyclines. Based upon the clinical observation that patients with acute promyelocytic leukaemia (APL) respond favourably to anthracyclines, we hypothesized that APL cells may have low levels of MDR1 expression. We therefore investigated MDR1 expression in 10 patients with APL and compared results with those obtained in 18 patients with other subtypes of acute myelogenous leukaemia (AML). Prior to reverse transcriptase polymerase chain reaction with MDR1 specific primers, leukaemic cells were purified by fluorescence activated cell sorting to exclude normal haemopoietic cells, in particular lymphocytes, from the MDR1 analysis. In sorted APL cells, MDR1 expression was detected in only two of 10 patients, which was significantly different from findings in other AML subtypes (MDR1 expression in 14/18 patients; P < 0.01). When unsorted specimens from APL patients were studied, five of six cases were MDR1 positive, whereas sorted APL cells were shown to express MDR1 mRNA in only one of these cases. MDR1 mRNA levels expressed as MDR1/beta-2 microglobulin ratios were significantly lower in APL (0.24 +/- 0.2, mean +/- SD) than in AML (0.75 +/- 0.48; P < 0.01). We conclude that low or absent expression of MDR1 in APL cells may contribute to the efficacy of anthracyclines in the treatment of APL. PMID- 7794758 TI - Polyclonal haemopoieses associated with long-term persistence of the AML1-ETO transcript in patients with FAB M2 acute myeloid leukaemia in continous clinical remission. AB - The t(8;21) (q22;q22) translocation is a recurring chromosomal abnormality observed in about 20-40% of AML patients with subtype FAB M2 (AML-M2). The molecular facet of this translocation is represented by the formation of a new hybrid gene, the AML1-ETO, which is regularly transcribed in a chimaeric mRNA and translated into a new fusion protein believed to have a key role in the pathogenesis of this type of leukaemia. We looked for the presence of AML1-ETO transcripts, by RT-PCR, in 49 unselected patients affected by AML-M2 diagnosed at various Italian Institutions. A hybrid transcript was detected in 11 cases (23%). Minimal residual disease status was investigated in three patients in continuous complete remission (CCR) after a median follow-up of 44 months; at least one sample from each subject was found positive for the AML1-ETO transcript suggesting a long-term persistence of t(8;21) leukaemic cells. In two female patients in CCR a 'clonality' analysis was performed on peripheral blood DNA by exploiting the X chromosome inactivation pattern of the human androgen-receptor gene (HUMARA); in both cases the results were consistent with the presence of a polyclonal haemopoiesis. Our data confirm that the persistence of residual cells expressing the AML1-ETO transcripts is a frequent occurrence even in patients with long-term remission; on the other hand, clonality assays indicate that in t(8;21) leukaemias long-term remission haemopoiesis is sustained by a polyclonal bone marrow reconstitution. PMID- 7794760 TI - Circumvention of P-glycoprotein-mediated drug resistance in human leukaemic cells by non-immunosuppressive cyclosporin D analogue, SDZ PSC 833. AB - Cyclosporin A (CSA) exhibits greater multidrug resistance (MDR) modulating activity in vitro than other MDR modulators such as verapamil and quinidine. However, the immunosuppressive and nephrotoxic effects of CSA may limit its clinical use. PSC 833, a new cyclosporin D derivative, exerts a higher MDR reversal activity but lacks toxic or immunosuppressive effects. The drug resistant sublines K/DAU100, K/DAU200, K/DAU300, K/DAU400, K/DAU500 and K/DAU600 have been derived from the drug-sensitive parental cell line, K562 cl.6 and CEM/VLB100 is a drug-resistant derivative of CCRF-CEM. We report a comparison of the effects of PSC 833 and CSA on daunorubicin (DAU) transport kinetics and chemosensitivity in these cell lines. Both CEM/VBL100 and K562 cl.6 DAU-resistant cells displayed high levels of P-glycoprotein (PGP), decreased DAU accumulation and increased DAU efflux when compared to their parental cells. PSC 833 was 1.6-, 3.4-, 4.9- and 4.6-fold more effective than CSA in reversing DAU resistance in higher resistance CEM/VLB100, K/DAU400, K/DAU500 and K/DAU600 cells respectively. DAU transport kinetics showed that PSC 833 was more effective than CSA in increasing cellular DAU accumulation and decreasing DAU efflux in higher resistant leukaemia subclones. PSC 833 could restore DAU retention at lower doses and was more active than CSA in all the resistant cells. A 89-100% restoration of intracellular DAU retention were gained by PSC 833 at 1.0 microM in K562 cl.6 DAU resistant sublines, whereas a 73-100% restoration of DAU retention was obtained by CSA only at 30.0 microM in the same resistant sublines. PSC 833 at 3.0 microM is sufficient to restore full DAU retention in all resistant cells. CSA, however, even at 30.0 microM, cannot confer full restoration of DAU retention in higher resistance K562 cl.6/DAU sublines. By measuring MDR modulator-mediated short-term inhibition of PGP function, PSC 833 was found to be at least 10-30 times more active than CSA. As no effect on DAU retention and sensitivity has been found in sensitive parental cells with PSC 833, it is suggested that PSC 833 may act by blocking the effluxing function of PGP in the resistant leukaemia cells. PMID- 7794761 TI - GST-pi and P-170 co-expression in multiple myeloma. AB - Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione-S-transferase pi (GST pi), P-glycoprotein and the protein product of ras oncogenes family, p-21, on plasma cells, by immunocytochemical detection. 72% of evaluated samples were positive for P-170 and 82% for GST-pi without any correlation with clinical or prognostic parameters. A significant relationship between GST-pi expression and P 170 positivity was found and co-expression was observed in 91% of evaluated samples. Expression of P-170 and GST-pi was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST-pi or P-170 or both. Expression of p-21 was not associated with these mechanisms of drug resistance. These data suggest that different resistance mechanisms are present in multiple myeloma. PMID- 7794762 TI - T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease: two closely related entities? AB - T-cell-rich B-cell lymphoma (TCRBCL) is a recently described variant of non Hodgkin's lymphoma. It may arise de novo or secondary to follicular lymphoma and large B-cell lymphoma. We present here seven cases of TCRBCL to emphasize a peculiar relationship to lymphocyte-predominant Hodgkin's disease. Morphologically, the neoplastic populations of all TCRBCLs, in addition to centroblast-like and immunoblast-like cells, comprised a few L+H-like elements. These neoplastic cells were all regularly scattered in a majority of reactive small T-lymphocytes as well as histiocytes. Moreover, tumour cells of TCRBCL, including the L+H-like elements of TCRBCL, expressed LCA and L26 but did not stain for Leu-M1 and BerH2, as is the case with the Reed-Sternberg cell L+H variant of lymphocyte-predominant Hodgkin's disease. Furthermore, the L26 immunoreaction in one of the cases, which otherwise presented as typical TCRBCL, disclosed a small subcapsular area resembling nodular paragranuloma because some few foci consisting of mature B lymphocytes with occasional L+H-like elements were seen. This also holds true for a second of the TCRBCLs presented that obviously coexisted with recurrent Hodgkin's paragranuloma 10 years after the primary manifestation. These findings indicate a close connection between TCRBCL and lymphocyte-rich Hodgkin's disease, and it may even be speculated as to whether TCRBCL represents merely a phenotypically different manifestation of this Hodgkin's subtype. Although the data presented here will not provide sufficient proof of this hypothesis, it seems clear that the nosology of TCRBCL in the context of current lymphoma classifications requires further elucidation. PMID- 7794763 TI - Biallelic DNA rearrangements and deletions within the BCL-6 gene in B-cell non Hodgkin's lymphoma. AB - Chromosomal translocations involving band 3q27 are recently described common specific cytogenetic abnormalities in B-cell neoplasms, and the BCL-6 gene, identified on 3q27, was shown to be disrupted and over-expressed in lymphoma cells having these chromosomal translocations. In the present study we found rearrangements within the BCL-6 gene in seven out of 35 cases with B-cell non Hodgkin's lymphoma (NHL). Further analysis revealed that three of these patients with BCL-6 abnormality had multiple rearranged bands hybridized with probes from a single restriction fragment within the major translocation cluster (MTC), suggesting that independent DNA rearrangements would occur on both alleles. Additionally, Southern blot analysis indicated that three patients carry deletions encompassing the area containing the first exon of the BCL-6 gene. Our results suggest that biallelic DNA rearrangements and deletions would occasionally occur in NHL patients with BCL-6 abnormality. PMID- 7794764 TI - Atypical chronic lymphocytic leukaemia with t(11;14)(q13;q32): karyotype evolution and prolymphocytic transformation. AB - In order to define better the cytological and clinical features of atypical B cell chronic lymphocytic leukaemia (B-CLL) with t(11:14)(q13;q32), sequential morphologic immunological and cytogenetic studies were performed in seven patients belonging to a series of 72 consecutive cases presenting with a diagnosis of CLL or atypical CLL according to the FAB criteria. Cytologic diagnosis in these seven patients with t(11;14) was typical CLL in two cases presenting with < 10% large lymphocytes (LL) and prolymphocytes (PL) and atypical CLL in five cases in which LL and PL comprised between 10% and 55%. The diagnosis was supported by histologic findings on bone marrow biopsy (five cases) or splenectomy specimens (two cases). A progressive increase of peripheral LL and PL was observed, resulting in a switch of FAB diagnosis over a 6-60-month period from typical CLL into atypical CLL in two cases and from atypical CLL into prolymphocytic leukaemia in five cases. Immunophenotyping showed a mature B-cell phenotype with CD19, CD22, CD24 positivity and CD10 negativity in all patients. A bright-staining pattern for surface immunoglobulins (SIg) was detected in 6/7 cases, CD5 positivity in 6/7 cases, and CD23 positivity in 1/7 cases. The FMC-7 monoclonal antibody was positive in > 40% cells in 5/6 cases. Chromosome changes in addition to t(11;14) were seen in five cases; in two cases unbalanced translocations involving the 3q21 chromosome region, resulting in partial trisomy for the long arm of chromosome 3, were detected early in the course of the disease. Karyotype evolution that was associated with disease progression occurred in 3/6 assessable patients. Comparison of these findings with similar data from 65 B-CLL patients without t(11:14) showed that atypical morphology, switch of FAB diagnosis during the course of the disease, and karyotype evolution were more frequently seen in cases with t(11;14) (5/7 v 15/65 cases, P = 0.015, 7/7 v 7/65 cases, P < 0.0001, and 3/6 v 5/45 assessable cases, P = 0.04, respectively). The frequency of positivity for CD23 and bright SIg staining differed significantly in the two groups. It is concluded that t(11;14) identifies a cytologically atypical subset of B-CLL, characterized by frequent cytologic and cytogenetic evolution and by a distinct immunological profile, sharing some biological features with mantle cell lymphoma. PMID- 7794766 TI - Characterization of protein disulphide isomerase released from activated platelets. AB - Protein disulphide isomerase (PDI) activity is released by activated platelets. In this study, PDI was purified from platelets and found to have an apparent mass, pI and N-terminal sequence similar to those for other human PDIs. Rabbit antibodies were generated and used to establish that, on activation, platelets release a protein immunologically identical to PDI in platelets. Approximately 10% of total platelet PDI was released by thrombin and 20% by calcium ionophore. The antibody was used to demonstrate PDI on the external surface of platelets by electron microscopy. Flow cytometry was used to demonstrate that upon activation of platelets with ionophore PDI was released by vesiculation. Since platelets are present and become activated at sites of vascular injury, platelet PDI may play a role in the various haemostatic and tissue remodelling processes in which platelets are involved. PMID- 7794767 TI - An ELISA for factor X activation peptide: application to the investigation of thrombogenesis in cardiopulmonary bypass. AB - An ELISA for measurement of factor X activation peptide (FXAP) in plasma has been developed. The capture antibody was generated by immunization with a carrier coupled synthetic peptide based on the amino acid sequence of the C terminal region of native human FXAP: the tag antibody was a commercial polyclonal antibody to factor X. Because of limited specificity of the capture antibody to FXAP compared with factor X, a plasma processing step precipitated plasma factor X and also permitted a concentration step, enabling detection of FXAP below the lower limit of the normal range in plasma. The overall intra- and inter-assay coefficients of variation were approximately 5% and approximately 11%, respectively. 18 normal laboratory control subjects had FXAP levels of 2.12 +/- 0.82 ng/ml (mean +/- SEM). Eight patients undergoing surgery and cardiopulmonary bypass progressively generated FXAP throughout the surgery with mean FXAP rising to 11.73 +/- 4.66 ng/ml, and this resulted in increased generation of thrombin detected by measurement of plasma levels of F1 + 2. Levels of FXAP rose significantly ahead of those of factor IX activation peptide (FIXAP), supporting a suggestion that contact system activation can not be the primary stimulus to coagulation in bypass. The ELISA to FXAP will be useful in the study of mechanisms of thrombogenesis in clinical situations where the coagulation system is activated. PMID- 7794765 TI - Establishment and characterization of IRTA17 and IRTA21, two novel acute non lymphocytic leukaemia cell lines with t(16;21) translocation. AB - The t(16;21)(p11;q22) translocation is an infrequent chromosomal abnormality, but seems specific to acute non-lymphocytic leukaemia (ANLL). We established two cell lines with t(16;21)(p11;q22) from the bone marrow of a patient with ANL in relapse. Their morphological, karyotypic, immunohistochemical and genetic features are examined. Although both cell lines show monocytoid features morphologically, they express only CD13 (My7) and CD34, and neither expressed monocytoid or lymphoid markers. Reverse transcription-polymerase chain reaction showed that both cell lines expressed a similar TLS-ERG chimaeric mRNA as a result of the t(16;21)(p11;q22) translocation. As far as we know, there is no report of a leukaemia cell line with t(16;21). These cell lines represent a useful tool for leukaemia research. PMID- 7794768 TI - The effect of endogenous oestradiol levels on protein S concentration during a menstrual cycle and after GnRH analogues and gonadotropin therapy. AB - We studied two groups of females to investigate the effect of endogenous oestradiol levels on total and free protein S (tPS, fPS) plasma concentrations. One group (group I) consisted of 12 healthy volunteers who were studied throughout one menstrual cycle; the other group (group II) consisted of 16 young women who were treated with GnRH analogues and gonadotropins before undergoing in vitro fertilization. Neither tPS nor fPS varied significantly with respect to the physiological changes of oestradiol or to the very low and high levels of oestradiol, achieved after GnRH analogues suppression and gonadotropin stimulation. These results indicate that endogenous oestradiol does not affect PS concentration. PMID- 7794769 TI - Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients. AB - The molecular characterization of mutations in haemophilia A patients in this study was carried out by PCR-SSCP, Southern blotting, and reverse transcribed PCR. A multiplex PCR in which four to eight exons were co-amplified was developed to reduce the time needed for screening the coding region of the factor VIII gene. PCR-SSCP was used to screen for small molecular defects, and reverse transcriptase PCR combined with Southern blotting was used to screen DNA for the inversions that occur frequently in intron 22 of the factor VIII gene. A group of 35 haemophilia A patients was analysed by these methods and 31 mutations were detected. In one patient two mutations were identified. The cases of mild and moderate haemophilia A showed changes in single nucleotides which predicted amino acid changes. The patients affected by severe haemophilia A showed two types of mutations. First, deletions or insertions that result in a frameshift in the coding DNA sequence were observed. Second, inversions were found which result in a disruption of the gene. With the screening strategies used we succeeded in elucidating an abnormality in the factor VIII gene in 30/35 haemophilia A patients. PMID- 7794770 TI - Severe hypophosphataemia during stem cell harvesting in chronic myeloid leukaemia. AB - Peripheral blood stem cell autografts for the treatment of chronic myeloid leukaemia (CML) are currently under evaluation. A patient with CML received intensive chemotherapy followed by granulocyte colony-stimulating factor prior to the collection of peripheral blood derived stem cells. He developed unusually severe, and fatal, hypophosphataemia and this coincided with the rapid rise of his peripheral blood white cell count. The hypophosphataemia was considered to be due to a combination of severe anorexia, sepsis and the rapid growth factor stimulated myeloid regeneration in CML. PMID- 7794773 TI - Karyotypic evolution in a granulocytic sarcoma developing in a myeloproliferative disorder with a novel (3;4) translocation. AB - A 59-year-old man presented with a granulocytic sarcoma arising in the manubrium, and splenomegaly. The blood count showed 1.2 x 10(9)/l eosinophils and a marrow aspirate was hypercellular with eosinophilia. Cytogenetic analysis of the marrow revealed a novel t(3;4) (p13;q12) and analysis of cells aspirated from the granulocytic sarcoma showed the same abnormality and an additional trisomy 8. Intensive chemotherapy and local radiotherapy led to resolution of the chest mass but persistence of the chromosome translocation in the marrow. PMID- 7794772 TI - CMV viraemia demonstrated in the serum of a patient with cytomegalovirus pneumonia. AB - We attempted to demonstrate the expression of cytomegalovirus (CMV) particles in the serum of an acute lymphocytic leukaemia patient with CMV pneumonia. The serum sample was applied to an affinity column coupled with human monoclonal antibody C23 which recognizes the envelope glycoproteins of CMV virus and neutralizes the viral activity. The DNA obtained from each fraction was amplified by double polymerase chain reaction (PCR) and analysed by gel electrophoresis. Bands were clearly observed in the eluted fraction. These results strongly suggest that CMV particles exist in the sera of patients with CMV pneumonia. PMID- 7794774 TI - Persistence of multilineage host haemopoiesis following allogeneic bone marrow transplantation. AB - The survival of host cells following high-dose cytotoxic therapy and allogeneic marrow transplantation has been established previously, but the identity of these cells has not been elucidated in detail. Four patients who received sex mismatched marrow have been studied for up to 12 months post-transplant using a simultaneous immunophenotyping/fluorescence in situ hybridization technique. The results demonstrate residual host T cells (CD3+), B cells (CD22+) and myeloid cells (CD11c+ and CD13+), and additionally cells of progenitor cell phenotype (CD34+). The long-term persistence of host haemopoiesis may have major relevance to the post-transplant complications of marrow rejection, graft-versus-host disease, and malignant relapse. PMID- 7794771 TI - Macrophage colony-stimulating factor-producing malignant histiocytosis. AB - We describe a patient with malignant histiocytosis who had a prominent neutrophilia uncommonly observed in this disease. Serum concentration of macrophage colony-stimulating factor (M-CSF) was markedly elevated, and correlated with clinical symptoms and neutrophil counts during clinical course. Moreover, M-CSF was detected in the cytoplasm of malignant histiocytes of the lymph node and bone marrow by immunohistochemical staining. These results indicate that the neutrophilia observed in this patient was caused by M-CSF produced by the malignant histiocytes. PMID- 7794776 TI - Dapsone for refractory chronic idiopathic thrombocytopenic purpura. AB - Fifteen patients with refractory chronic idiopathic thrombocytopenic purpura (ITP) were treated with dapsone (100 mg/d) for 1-31 months. The overall response rate to dapsone was 40%. Five patients responded in 1 month and one patient in 2 months. No pretreatment characteristics--sex, age, platelet count or duration of ITP--were correlated with response to dapsone. Treatment was well tolerated. The most frequent adverse effect was dose-related haemolytic anaemia. In our experience, dapsone provides an inexpensive and well-tolerated alternative for patients with ITP who had inadequate responses to conventional therapy. PMID- 7794775 TI - Pearson's marrow/pancreas syndrome: haematological features associated with deletion and duplication of mitochondrial DNA. AB - Pearson's marrow/pancreas syndrome (PS) is a rare, often fatal, disorder of infancy that is characterized by impaired bone marrow, exocrine pancreatic, hepatic and renal function. Large-scale rearrangements of mitochondrial DNA (mtDNA) are present in blood. We report a patient with PS who has predominantly impaired haemopoiesis manifesting as sideroblastic anaemia, vacuolization of bone marrow precursors, and neutropenia. 77% of bone marrow mtDNA was rearranged (64% deleted an 13% duplicated). We suggest that rearrangements of mtDNA should be sought in all infants presenting with sideroblastic anaemia. PMID- 7794777 TI - Deletion of chromosome 13 (band q14) but not trisomy 12 is a clonal event in B chronic lymphocytic leukaemia (CLL). AB - Chromosomal abnormalities are detected by conventional cytogenetic or FISH analysis in 50% of chronic lymphocytic leukaemias (CLL). Trisomy 12 and del 13q14 account for 70% of these abnormalities. The incidence of these two abnormalities was studied in CLL patients by Southern blot analysis using a highly purified B cell malignant population (CD5 > 95%, CD3 < 5%). Probes for the D13S25 marker on chromosome 13 band q14 and for the RBTN3 gene on chromosome 12 band p12-13, were used. Deletion of the D13S25 was detected in 17/42 patients (43%) in a homozygous (9.5%) or heterozygous (30%) configuration. Deletion of the D13S25 marker appears to be a clonal and early event in CLL development since it is detected in > 95% of the malignant clonal population. Conversely, trisomy 12 is rarely a clonal event (5/33 patients, 15%) and a varying proportion of cells carrying this abnormality can be demonstrated in 30% of CLL patients (10/33 patients). PMID- 7794778 TI - Coronary artery bypass surgery in patients with inherited antithrombin deficiency. AB - Antithrombin (AT) replacement in coronary artery bypass grafting procedures in three individuals with inherited antithrombin deficiency is described. All three had a significant personal or family history of thrombotic disease. All patients achieved satisfactory AT levels throughout bypass and in the postoperative period. All received heparin prophylaxis in the postoperative period. None suffered thrombotic or bleeding complications. PMID- 7794779 TI - A promoter mutation, C-->T at position -92, leading to silent beta-thalassaemia. AB - This study describes the clinical phenotype of the C-->T mutation at position -92 of the beta-globin gene. Excluding two cases with HbA2 levels within the range of the beta-thalassemia carrier state, heterozygotes for this mutation showed normal or borderline red blood cells count, Hb levels, MCV, MCH and HbA2 values, and unbalanced globin chain synthesis. Compound heterozygotes for the -92 C-->T mutation and a beta zero-thalassaemia mutation (beta zero 39) (two cases) or severe beta+-thalassaemia (beta+ IVSII nt 745) (two cases) developed thalassaemia intermedia. According to these characteristics, the -92 promoter mutation should be added to the list of silent beta-thalassaemias. PMID- 7794780 TI - Therapy-related acute myeloblastic leukaemia (M1) with a 9;11 translocation. PMID- 7794781 TI - A stage-theory model of cognitive development. AB - A model of the proportions of the population at various stages of cognitive development as a function of age is proposed. It is shown that a number of weaknesses in an earlier model proposed by Eckstein & Shemesh (1992a) are avoided. The new model accounts well for empirical data for the age range 13-18 years. The uses of such models in research are discussed. PMID- 7794782 TI - A model of Pavlovian conditioning: variations in representations of the unconditional stimulus. AB - We present a model of Pavlovian excitatory conditioning in which associative strength and malleable central representations of unconditional stimuli determine the strength of conditional responding. Presentation of a conditioned stimulus acts through an experientially determined associative bond to activate a representation of the unconditional stimulus. The activation of the representation produces a conditioned response. A striking feature of the model is its ability to describe changes in conditioned response magnitude in terms of alterations of representations of the unconditional stimulus. Another is its acknowledgement of the capacity of associative bonds to survive behavioral extinction. The model describes much of the data reported from excitatory conditioning experiments and predicts counterintuitive phenomena. PMID- 7794783 TI - Dogmas that have hindered understanding. PMID- 7794784 TI - Effects of cold on human information processing: application of a reaction time paradigm. AB - Only a very few studies on the effects of cold on human information processing appear to exist. Therefore, the present experiment was designed to study the effects of the experimentally induced lowering of body core temperature on information processing, while applying a reaction time paradigm. Thirty healthy male volunteers performed a stimulus evaluation-response selection reaction time task after exposure to ambient temperatures of either 28 or 5 degrees C. A 0.5 degree C-decrease in body core temperature resulted in a significant increase in both reaction and movement time indicating a general deteriorating effect of lowering of body core temperature on information processing. Mean reaction times were 538 ms and 549 ms for the control and the cold group, respectively (p < .05). The respective mean movement times were 298 ms and 269 ms (p < .001). Speed of stimulus evaluation was not sensitive to decreases in body core temperature. However, response complexity and body core temperature showed a significant interaction in their effect on movement time (p < .05), indicating that lowering of body core temperature is more likely to affect response-related stages of central information processing rather than stimulus evaluation. Furthermore, movement time appeared to be more sensitive to cold-induced effects on information processing as compared to reaction time. Additional correlational analyses suggest that the observed effects can be considered as independent of changes in skin temperature and experienced levels of thermal discomfort. Taken together, the results indicate that lowering of body core temperature differentially affects various stages of information processing. PMID- 7794786 TI - Shortening of the QT interval of the EKG is associated primarily with increased ventricular contractility rather than heart rate. AB - The objective of this study was to gather direct evidence on whether the duration of the QT interval relates primarily to heart rate or to ventricular contractility. The electrocardiographic and cardiodynamic consequences of electrical stimulation (15 V, 5 ms, 10Hz) of various intrathoracic sympathetic efferent neuronal structures were studied in 10 anesthetized mongrel dogs. Stimulation of efferent sympathetic axons in the right intraganglionic nerve, which innervates the sinoatrial node, induced tachycardia (110 +/- 5 - 133 +/- 6 bpm; p < 0.01) without significantly altering right or left ventricular intramyocardial ventricular chamber pressures. The QT interval, as determined by leads I, II and III of the EKG and a transthoracic lead, was not affected by this intervention 310 +/- 8 - 302 +/- ms). Increasing heart rate to a similar degree (111 +/- 3 - 131 +/- 3 bpm) by right atrial pacing did not induce changes in the QT interval. When right (23 +/- 3 - 49 +/- 8 mm Hg; p < 0.01) and left (81 +/- 10 - 127 +/- 19 mm Hg; p < 0.01) ventricular forces were augmented without concomitant increases in heart rate by stimulating efferent sympathetic axons in the left caudal pole cardiopulmonary nerve the QT interval shortened (322 +/- 11 290 +/- 12 ms; p < 0.01). Only when an efferent sympathetic nerve, that contains fibers destined for both the sinoatrial node and the ventricles was stimulated did both heart rate and ventricular contractility augment and QT shorten (318 +/- 10 - 290 +/- 11 ms; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794785 TI - A behavioral link between the oculomotor and cardiovascular systems. AB - Although the eyes and the heart serve very different purposes, each receives autonomic innervation. Capitalizing on recent theoretical and technological innovations in the understanding and assessment of oculomotor and cardiovascular behavior, three experiments measured behavioral covariation between the oculomotor and cardiovascular systems. Measures of dark focus and dark vergence indexed oculomotor tone, and the spectral decomposition of variations in heart rate indexed cardiovascular control mechanisms. In Experiment 1, individual differences in cardiovascular parameters could predict individuals' dark vergence (R2 = .806) but not their dark focus (R2 = .404). In Experiment 2, the same parameters were measured from subjects who experience either panic attacks (n = 11) or blood phobia (n = 9). Heart rate was positively correlated with dark vergence and the two subject groups were separable based on both oculomotor and cardiovascular variables. Using a within-subjects approach, Experiment 3 found that both dark vergence and dark focus tended to be nearer during sympathetic dominance of the heart than during parasympathetic dominance, within-subjects variations in cardiovascular parameters could predict dark focus, and between subjects variations in interbeat intervals could predict dark vergence. Shared patterns of autonomic activation may be responsible for this eye-heart link. PMID- 7794788 TI - The electrocardiograph. PMID- 7794789 TI - Psychosocial forces and neural mechanisms in disease: defining the question and collecting the evidence. Essay review. PMID- 7794787 TI - Sick-building syndrome fatigue as a possible predation defense. AB - Sick-building syndrome is an illness characterized by fatigue, headache, and upper-respiratory complaints. It is usually associated with modern office buildings, structures with an impervious outer shell and inoperable windows. Poor air quality, specific pollutants, and inadequate ventilation are considered common causes. The ability to smell faint odors requires air that is free of contamination. Human evolutionary ancestors depended on odors for survival. Even the slightest increase in the ability to smell a predator conveyed a distinct, immediate survival advantage. Conversely, an enormous survival advantage would also accrue to the animal that sought protection or avoided activity when this vital olfactory information was unavailable. Such would be the case with fire on the savannah. The foraging, olfactory dependent animal, unable to smell predators because of contaminated air, would be quickly snatched by a keen-sighted carnivore. There exist, however, well-described reflexes from the nose mediated through the trigeminal nerve that discourage activity when these free nerve endings are irritated. This mechanism may serve as a defense against predation. In adulterated atmosphere the animal, subdued by these reflexes, would be less likely to venture forth and, therefore, less vulnerable to predators. Similar reflexes may persist in humans, activated by poor air quality, air ill-suited for the dissemination of odors. I suggest that the human perception of these inhibitory reflexes is the feeling of fatigue associated with the sick building syndrome. PMID- 7794790 TI - Nuclear factor I interferes with transformation induced by nuclear oncogenes. AB - The four nuclear factor I genes (NFI-A, NFI-B, NFI-C, and NFI-X) give rise to multiple isoforms by alternative splicing in many tissues. These NFI proteins cooperate with AP-1, Myc, and other transcription factors in regulating transcription of numerous cellular and viral genes. We have investigated the growth-regulatory potential of NFI by overexpressing cDNAs from chicken NFI genes -A, -B, -C, and -X in chicken embryo fibroblasts (CEF). None of the NFI cDNAs induced oncogenic transformation of CEF. However, overexpression of each of the NFI proteins caused similar morphological alteration of the cells, inducing them to become flattened and polygonal and to show increased adherence. The growth properties of these cells were similar to normal CEF. When these morphologically altered CEF were challenged by superinfection with oncogenic retroviruses, they were resistant to transformation by the nuclear oncogenes jun, fos, junD, myc, and qin but were readily transformed by cytoplasmic oncogenes src, mil/raf, ras, and fps. The NFI-A1 protein was able to alter transactivation by the cellular and viral Jun proteins in a promoter-dependent manner. The changes in cell morphology and reduced susceptibility to nuclear oncogenes were not seen with a carboxy terminal truncation in the transactivation domain of NFI, suggesting that this region of the protein is essential for the observed effects. The dichotomy between the activities of nuclear and of cytoplasmic oncogenes in this system is discussed. PMID- 7794791 TI - A direct role of transcription factor E2F in c-myc gene expression during granulocytic and macrophage-like differentiation of HL60 cells. AB - The transcription factor E2F is known to play an important role in cell cycle progression through interaction with retinoblastoma protein. HL60 cells are able to differentiate into a granulocytic lineage by prolonged exposure to retinoids and into a macrophage-like lineage by exposure to tumor promoter 12-O tetradecanoylphorbol 13-acetate, with a rapid decrease of c-myc gene expression. In this study, we assessed the changes of the E2F-binding pattern to the P2 promoter region of the c-myc gene during differentiation into both lineages. The observed changes of the E2F-binding pattern were a decrease of free E2F and an appearance of retinoblastoma protein-containing E2F complexes in both lineages. The effects of the anti-c-myc antibody and the recombinant c-Myc protein on the E2F-binding patterns suggest that the c-Myc protein is not involved directly in these changes. These changes also led the suppression of transcriptional initiation from the P2 promoter. The results indicate that, in the course of HL60 cell differentiation, E2F plays a direct role in the transcriptional control of the c-myc gene through interaction with the retinoblastoma protein. A potential role for the c-Myc protein is discussed in relation to an existing state of E2F and E2F-RB complexes in the HL60 cells. PMID- 7794792 TI - Apoptosis in Pam212, an epidermal keratinocyte cell line: a possible role for bcl 2 in epidermal differentiation. AB - Programmed cell death is a controlled process that leads to the elimination of single cells via apoptosis, a mode of cell death with a characteristic morphology. During epidermal differentiation, keratinocytes migrate outward to become terminally differentiated cornified cells in a process involving programmed cell death pathway(s) and apoptosis. The molecular mechanisms regulating epidermal differentiation and apoptosis have not yet been elucidated. Here we show that a mouse keratinocyte cell line, Pam212, undergoes spontaneous apoptosis in culture. Apoptosis of Pam212 cells is demonstrated by both morphology and DNA oligonucleosomal degradation. The expression of bcl-2, a gene implicated in the negative control of apoptosis, was down-regulated in these cells by transfecting a bcl-2-antisense expression vector. The cells that down regulate bcl-2 expression exhibit enhanced apoptosis and further progress in the epidermal differentiation pathway. We analyzed the expression patterns of several genes that have been implicated in apoptosis in other systems. We show that the mRNA levels of c-myc, c-myb, c-fos, tumor necrosis factors (TNF) alpha and beta, TNF receptors I and II, interleukin 1 alpha, IFN-gamma, and transforming growth factor beta increase in the antisense-transfected cells. We suggest that bcl-2 influences epidermal differentiation in Pam212 keratinocyte cells, and maybe in vivo, by negatively regulating several genes that are involved in apoptosis. PMID- 7794794 TI - Insulin-like growth factor II overexpression in myoblasts induces phenotypic changes typical of the malignant phenotype. AB - The objective of this study was to examine the role of insulin-like growth factor II (IGF-II) in the pathogenesis of human rhabdomyosarcomas (RMS). We have demonstrated previously that RMS express high levels of IGF-II mRNA, secrete IGF II peptide, and express both IGF-I and IGF-II receptors. Moreover, we showed that IGF-II functions as an autocrine growth and motility factor in RMS. Since IGF-II is expressed at high levels in fetal muscle cells and RMS are tumors thought to derive from skeletal myoblasts arrested along the normal myogenic pathway, autocrine production of IGF-II by RMS may be an etiological event in the development of this tumor. We have developed a model system which enabled us to study the effects of endogenous IGF-II overprotection in muscle myoblasts. Human cDNA for pre-prohormone IGF-II was transfected into mouse myoblasts in order to achieve high, constant expression of this growth factor, which is normally down regulated at the end of the differentiation process. Expression of high IGF-II levels resulted in: (a) an increased proliferative rate; (b) impairment of the ability to differentiate into myoblasts; and (c) acquisition of the capability of anchorage-independent growth. No changes in the expression of IGF-I receptors were noted. We conclude that IGF-II overexpression in muscle myoblasts induces morphological and biological changes typical of the malignant phenotype and represents a fundamental event in the pathogenesis of RMS and possibly of other embryonal tumors. PMID- 7794795 TI - Serum growth factors up-regulate H-ras, K-ras, and N-ras proto-oncogenes in fibroblasts. AB - We have analyzed the expression of the ras gene family during the transit through quiescence-proliferation. H-, K- and N-ras steady-state mRNA levels and total Ras protein levels did not change significantly when NIH3T3 cells were made quiescent by density arrest in the presence of 10% calf serum. By contrast, levels of ras mRNAs in cells that had been made quiescent by serum deprivation were lower than those in growing cells. An induction of H-, K- and N-ras mRNA levels (3- to 5 fold) was detected in these cells after serum addition. This induction was maximal around 8 h after serum addition for the three ras genes. Like the early response genes, ras induction was not dependent on protein synthesis; but in contrast to these genes, ras mRNAs showed long half-lives (5-7 h) in NIH3T3 cells. Up-regulation of ras genes by serum was also observed in human primary fibroblasts, indicating that this may be a general effect in mammal cells. We obtained stable transfectants in NIH3T3 cells with the oncogenic N-ras. In these cells, expression of the transforming gene is also induced by serum, and the expression of the transfected N-ras gene did not modify the response to serum of endogenous H-, K-, and N-ras genes. The regions of murine N-ras gene responsible for serum inducibility seem to be intragenic because N-ras up-regulation occurred in cells transfected with a gene construct lacking the sequences upstream from the first exon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794796 TI - Epithelial rat thyroid cell clones, escaping from transforming growth factor beta negative growth control, are still inhibited by this factor in the ability to trap iodide. AB - Transforming growth factor beta (TGF beta) acts on epithelial thyroid cells, negatively controlling their proliferation and functions. The effects of TGF beta on epithelial rat thyroid cells (FRTL-5) and on two TGF beta-resistant rat thyroid cell clones (FRTL-5H2 and FRTL-R) were investigated. FRTL-5H2 represents a rat thyroid cell clone overexpressing active erbB-2 oncogene, recently obtained after FRTL-5 cell infection with a retrovirus vector carrying the erbB-2 human oncogene (G. Mincione et al., Cancer Res., 53: 5548-5553, 1993). FRTL-R is a FRTL 5 subclone spontaneously isolated after long term in culture. FRTL-5H2 and FRTL-R cell clones were stimulated by TGF beta at the same concentration of 5 ng/ml that induced 70% inhibition of [3H]thymidine incorporation in control FRTL-5 thyroid cells. Nuclear events regulated by TGF beta, such as cyclin and cyclin-dependent kinase gene expression, were then analyzed. In FRTL-5 cells, TGF beta was found to reduce the expression of cdk2 and cyclin A genes; the same treatment did not modify nuclear gene expression in the resistant cell clones. TGF beta is known to reduce iodide uptake in thyroid cells; in both FRTL-5H2 and FRTL-R cells, TGF beta was found to inhibit the thyrotropin-induced iodide uptake. Thus, thyroid cell clones, resistant to the growth-inhibitory activity of TGF beta, were sensitive to TGF beta inhibition of iodide incorporation, suggesting that TGF beta activates divergent signaling pathways in these cells, separately controlling cell proliferation and differentiation parameters. Studies on TGF beta receptors showed similar amounts of TGF beta-binding species on FRTL-5 cells and TGF beta-resistant clones, while 125I-labeled TGF beta cross-linking experiments revealed differences; thus, the TGF beta-resistant cells showed a 40% decrease in the amount of labeled type II TGF beta receptor on the cell surface. However, this different pattern of TGF beta receptors cannot totally account for the shown TGF beta resistance to growth inhibition that might also be due to perturbation in signaling pathways. PMID- 7794793 TI - Differential dependence of the tumorigenicity of chemically transformed rat liver epithelial cells on autocrine production of transforming growth factor alpha. AB - The tumorigenic phenotype in rat liver epithelial cells overexpressing c-myc may depend on a transforming growth factor (TGF)-alpha/epidermal growth factor receptor autocrine loop (L. W. Lee et al., Cancer Res., 51: 5238-5244, 1991). In the present study, we have used constitutive sense and antisense TGF-alpha expression vectors to modify TGF-alpha production in carcinogen-transformed clonal derivatives of a rat liver epithelial cell line, WB-F344, that variably express c-myc, endogenous TGF-alpha, and tumorigenicity. Transgene-mediated TGF alpha protein production was elevated 2- to 9-fold in derivatives of a low c-myc expressing transformed cell line, GN4, and 35-fold in a derivative of a high c myc-expressing cell line, GN6. Although the GN4- and GN6-derived cell lines expressed functional EGF receptor and steady-state c-myc mRNA levels that were comparable to their respective parental cell lines, increased TGF-alpha expression did not increase the tumorigenicity of the derivatives relative to the parental cell lines. Similarly, in vitro growth characteristics of the GN4- and GN6-derived cell lines were not markedly altered by increased autocrine TGF-alpha production. Additionally, GN4, GN6, and their derivatives were, for the most part, unresponsive to exogenously applied TGF-alpha in vitro. In contrast, antisense TGF-alpha RNA expression significantly suppressed endogenous TGF-alpha production in a high c-myc-expressing, high TGF-alpha-expressing, highly tumorigenic clonal line, GP9; this suppression resulted in lowered steady-state c myc levels and attenuated in vitro growth. Antisense-mediated suppression of all of these in vitro phenotypes in GP9 was reversed by exogenous TGF-alpha. The latency of tumor formation by the antisense derivative of cell line GP9 was significantly lengthened (> 3-fold) relative to the time required for tumor formation by its parental cell line. These results demonstrate that a TGF alpha/epidermal growth factor receptor autocrine loop may be necessary for exaggerated in vitro and in vivo growth of some transformed rat liver epithelial cells (e.g., GP9); however, the autocrine loop is not generally sufficient to support tumorigenicity, even in transformed clonal lines expressing elevated levels of c-myc. PMID- 7794797 TI - Stimulation of receptor protein-tyrosine phosphatase alpha activity and phosphorylation by phorbol ester. AB - Receptor Protein-Tyrosine Phosphatase alpha (RPTP alpha) is a transmembrane protein with two cytoplasmic catalytic protein-tyrosine phosphatase (PTP) domains and a relatively short (123 amino acids) extracellular domain. Here we report that treatment of transfected cells that express RPTP alpha with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate, a direct activator of protein kinase C, induced a rapid, transient increase in RPTP alpha activity due to a 2- to 3 fold increase in substrate affinity. A transient increase in RPTP alpha serine phosphorylation was concomitant with the enhanced activity. Tryptic phosphopeptide mapping of RPTP alpha demonstrated that phosphorylation of three tryptic peptides was enhanced in response to phorbol ester. In vitro dephosphorylation of RPTP alpha from phorbol ester-treated cells reduced RPTP alpha activity to prestimulation levels, indicating that enhanced serine phosphorylation directly accounted for the increase in activity. Our results demonstrate that serine phosphorylation may play a key role in the regulation of the activity of transmembrane PTPs. PMID- 7794798 TI - Increased expression of diazepam binding inhibitor in human brain tumors. AB - Benzodiazepines, which are in extensive clinical use, can regulate neoplastic growth via benzodiazepine receptors. We have studied the expression of the diazepam binding inhibitor (DBI) polypeptide, a putative endogenous ligand for benzodiazepine receptors in normal and pathological human brain. In normal brain, DBI immunoreactivity (IR) and mRNA were detected in all brain areas, with the highest levels in the cerebellum, amygdala, and hippocampus. In light and electron microscope immunohistochemistry, DBI-IR was only detected in glial and ependymal cells. In brain tumors, such as astrocytomas, glioblastomas and medulloblastomas, a much higher content of DBI-IR and -mRNA was found in normal tissues. The highest level of DBI expression was found in the most anaplastic tumors. DBI-IR was virtually undetectable in meningiomas and pituitary adenomas. The high expression of DBI in brain tumors might play a role in the neoplastic growth of glial cells via the mitochondrial benzodiazepine receptor, or it may be involved in the regulation of the high energy consumption of these tumors via acyl-CoA metabolism. PMID- 7794799 TI - Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues. AB - The neurofibromatosis 1 (NF1) gene encodes a large M(r) approximately 250,000 phosphoprotein, the expression of which in adult tissues is limited to neurons, Schwann cells, oligodendrocytes, adrenal medulla, and leukocytes. The presence of two alternatively spliced exons (23a and 48a) in the NF1 gene allow for the generation of four possible neurofibromin isoforms. Type 1 neurofibromin contains neither 23a or 48a exon sequences, while type 2 neurofibromin contains only the 23a exon insertion. Previous studies have demonstrated that types 1 and 2 neurofibromin might have different functional properties relative to microtubule association and GTPase-activating protein activity towards p21-ras. To determine the normal pattern of expression of these NF1 isoforms, the adult and developmental expression of types 1 and 2 NF1 was examined. Herein, we demonstrate that NF1 mRNA is expressed at varying levels in adult tissues and is developmentally regulated during embryogenesis. Neurons in the central nervous system express predominantly type 1 NF1. Using mouse neocortical cultures enriched for neurons or glial cells, type 1 NF1 predominance was demonstrated in neurons, while type 2 NF1 predominated in glial cells. In contrast to central nervous system neurons, neurons expressing the type 2 NF1 isoform were identified in the developing dorsal root ganglia and spinal cord by in situ hybridization using a type 2-specific oligonucleotide probe. The elucidation of the differential expression pattern of these two NF1 isoforms during development and in adult life provides the foundations for future studies aimed at determining the functions of these neurofibromin isoforms. PMID- 7794800 TI - Expression of the v-Mos oncogene in male meiotic germ cells of transgenic mice results in metaphase arrest. AB - To explore the role of pp39mos in male germ cell meiosis, we have constructed transgenic mice carrying either the c-Mos or v-Mos genes linked to the human male germ cell-specific phosphoglycerate kinase-2 promoter. All male transgenic mice bearing the v-Mos but not the c-Mos construct were sterile due to arrest of germ cells at metaphase I. Immunocytochemistry performed on sections from control and c-Mos transgenic testes with eight different monoclonal and polyclonal antisera against either alpha-, beta- or gamma-tubulins demonstrated that all could recognize MI spermatocyte spindles from control and c-Mos transgenics, but only one monoclonal anti-microtubule sera decorated the spindles of v-Mos-arrested meiotic figures. Western blot analyses with this one serum revealed a change in proteins in the v-Mos samples. Immunocytochemistry with the MPM-2 monoclonal antibody, which is specific for epitopes phosphorylated during mitosis, demonstrated an increase in cytoplasmic and spindle-associated phosphoproteins in arrested v-Mos spermatocytes. Western analysis with MPM-2 showed an increase in a M(r) 50,000-55,000 and a M(r) 25,000-29,000 protein in Mos transgenic testes when compared to controls. An anti-MAP kinase antibody demonstrated an increase in all four MAP kinases in testes of transgenic mice. Thus, overexpression of pp39v-mos during male germ cell meiosis resulted in an alteration of various cell cycle related kinases and cytostatic factor-like arrest at MI. PMID- 7794801 TI - Coordinate regulation of Igf-2 and H19 in cultured cells. AB - The insulin-like growth factor 2 (Igf-2) and H19 genes are physically linked on mouse distal chromosome 7 and are reciprocally imprinted. We investigated the molecular basis of the parental imprints in somatic cell cultures derived from normal embryos or from their littermates with maternal uniparental disomy for distal chromosome 7 (MatDi7). In normal cells, the two genes appeared to respond to similar regulatory factor(s), since both genes were coordinately up-regulated upon growth arrest and cell clones which had lost expression of one gene had lost expression of the other. However, in a clone of MatDi7 cells (MatDi7 1-1a), which spontaneously began to express the maternally derived copy of Igf-2, Igf-2 and H19 were not coordinately regulated. MatDi7 1-1a cells showed de novo methylation of sites upstream of Igf-2 and also within the H19 promoter, epigenetic modifications normally seen only on the paternal chromosome. The data provide new experimental evidence for previously hypothesized mechanisms suggesting that Igf 2 and H19 are coordinately regulated. PMID- 7794803 TI - Apoptosis inhibition by anti-M(r) 23,000 (Thy-1) monoclonal antibodies without inducing bcl-2 expression. AB - Mouse malignant T-lymphoma CS-21 cells grow in vitro in the presence of CA-12 stromal cells, but they undergo apoptotic cell death with DNA fragmentation when cultured alone. Because apoptosis of CS-21 cells was not inhibited by soluble factors secreted from CA-12 stromal cells, cell-cell interactions between the two seemed to be important to inhibit apoptosis. We found that CS-21 cell adhesion was mediated by M(r) 168,000 and M(r) 23,000 proteins and that apoptosis inhibitory signals were transmitted through these proteins. In this study, we identified the M(r) 23,000 cell adhesion molecule as a glycosylphosphatidylinositol-anchored Thy-1 (CD90) glycoprotein. Cross-linking of M(r) 23,000 protein with anti-M(r) 23,000 mAb and a second antibody transiently raised the [Ca2+]i and activated calcineurin in CS-21 cells, as has been observed in normal T lymphocytes stimulated by cross-linking anti-Thy-1 mAbs. However, differing from normal T lymphocytes, CS-21 cells could grow either by the transient increase in [Ca2+]i or by the activation of protein kinase C. Furthermore, M(r) 23,000 protein-mediated cell survival of CS-21 cells was not accompanied by expression of the apoptosis-inhibiting protein bcl-2, although protein kinase C-activated cell survival was attended by bcl-2 expression. These results indicate that the M(r) 23,000 protein (Thy-1) of CS-21 lymphoma cells functions as a cell adhesion molecule capable of transducing signals of cell survival and growth that are not followed by bcl-2 expression. PMID- 7794802 TI - Overexpression of the class II P-glycoprotein gene in primary rat hepatocyte culture: evidence for increased mRNA stability. AB - The overexpression of P-glycoprotein (Pgp) appears to be responsible for multidrug resistance in some human cancers. The molecular basis of this overexpression is not understood. We have used primary monolayer cultures of adult rat hepatocytes as a model system to study the regulation of Pgp gene expression (Lee et al., J. Cell. Physiol., 157: 392-402, 1993). We observed a dramatic and specific overexpression of class II Pgp as a function of the time in culture. This isoform of Pgp, which is expressed at a very low level in normal liver, has also been shown to be predominantly overexpressed in several models of rat liver carcinogenesis. In the present study, we have used nuclear run-on assays and mRNA decay studies to investigate the mechanism for the overexpression of class II Pgp in cultured hepatocytes. We conclude that an increased mRNA stability is the major factor involved in the increased expression of class II Pgp. Studies using various drugs indicate that the integrity of the cytoskeleton is important for the maintenance of high expression of class II Pgp. Disruption of the cytoskeleton in cultured hepatocytes with cytochalasin D did not affect the transcriptional activity of the class II Pgp gene but rapidly destabilized its mRNA. This raises the possibility that an association between class II Pgp mRNA and cytoskeletal elements may underlie the mechanism that regulates class II Pgp mRNA stability. These findings have important implications for our understanding of the overexpression of class II Pgp during liver carcinogenesis. PMID- 7794804 TI - Overexpression of Bcl-XL by cytotoxic drug exposure confers resistance to ionizing radiation-induced internucleosomal DNA fragmentation. AB - Acquired resistance to diverse chemotherapeutic agents has been associated with overexpression of the P-glycoprotein. We have selected human U-937 cells for clones resistant to the cytotoxic agents doxorubicin (U-A20) and vincristine (U V20). The results demonstrate that P-glycoprotein-positive U-A20 and U-V20 cells exhibit resistance to inducers of internucleosomal DNA fragmentation. Although parental U-937 cells responded to ionizing radiation with the DNA laddering characteristic of physiological cell death, the drug-resistant lines were insensitive to this effect. The U-A20 and U-V20 clones were also resistant to endonucleolytic DNA cleavage associated with exposure to tumor necrosis factor or ceramide. Previous work has demonstrated that physiological cell death is inhibited by overexpression of the Bcl-2 protein. However, analysis of Bcl-2 revealed similar levels in the parental and drug-resistant cells. In contrast, we show that U-A20 and U-V20 cells overexpress the Bcl-2-related protein, Bcl-xL. Moreover, studies with a U-937 cell line transfected with a Bcl-XL expression vector confirm resistance to ionizing radiation-induced DNA fragmentation and cell killing. These findings suggest that, unlike Bcl-2, Bcl-XL may be constitutively overexpressed as a result of selection for cytotoxic drug resistance and that Bcl-XL participates in an acquired form of multimodality resistance to chemotherapeutic agents and radiation. PMID- 7794805 TI - Phorbol ester treatment of U937 cells with altered protein kinase C content and distribution induces cell death rather than differentiation. AB - Overexpression of protein kinase C (PKC)-zeta, an atypical PKC isoform, in U937 cells stimulates certain parameters of phenotypic maturation and increases expression of endogenous alpha and beta PKC isoforms. In response to 12-O tetradecanoylphorbol-13-acetate (TPA), parental U937 cells displayed growth arrest and differentiated into a monocyte/macrophage-like cell line, while PKC zeta cells underwent death. The ability of GF109203X to inhibit TPA-induced death of PKC-zeta cells suggested that activation of a conventional isoform was necessary to induce apoptosis. While exhibiting unique morphological changes, parameters indicative of a further degree of differentiation were not observed in TPA-treated PKC-zeta cells. TPA-induced down-regulation of PKC activity was similar in both cells. While modest quantitative differences in individual isoform down-regulation existed, intracellular localization of isoforms prior to activation differed significantly between U937 and PKC-zeta cells. Expression of gadd45 was induced by TPA in PKC-zeta but not parental cells and occurred as a primary response to TPA and prior to the onset of cell death. These data suggest that the decision of a cell to undergo death or differentiation in response to phorbol esters may, in part, be modulated by alterations within the PKC signal transduction pathway. PMID- 7794807 TI - G1 cyclins control the retinoblastoma gene product growth regulation activity via upstream mechanisms. AB - Inactivation of the retinoblastoma gene product (pRb) occurs concomitant with the appearance of its hyperphosphorylated form in mid to late G1. Multiple cyclin/CDK complexes are implicated in the cell cycle phosphorylation of pRb. Using in vivo expression systems, we show that cyclins A, E, D1, D2, and D3 each function to phosphorylate and inactivate pRb. In vivo, G1 cyclin/kinase complexes enhance the phosphorylation of pRb, and these effects of cyclin/kinases on pRb can be overcome by the addition of p21, a wide spectrum inhibitor of G1 kinases. Kinases associated with cyclins A, E, and D1 phosporylate pRb indistinguishably in vivo, according to proteolytic maps. Although cyclin D1 has been reported to bind to pRb directly, requiring the pRb-binding motif LXCXE, a mutant D1 lacking the pRb binding motif remains able to phosphorylate pRb in vivo and in vitro and is also able to reverse the growth-inhibitory properties of pRb in intact cells. Finally, coexpression of G1 cyclins and kinases represses pRb-mediated growth inhibition in Saos-2 cells. The multiplicity of mechanisms for pRb phosphorylation and inactivation suggests that several pathways exist for the regulation of pRb by phosphorylation. PMID- 7794806 TI - The human CCKB/gastrin receptor transfected into rat1 fibroblasts mediates activation of MAP kinase, p74raf-1 kinase, and mitogenesis. AB - The human cholecystokinin (CCK)B/gastrin receptor was stably transfected into Rat1 fibroblasts to examine the signaling pathways mediated by this seven transmembrane, G protein-linked receptor. We report here that binding of CCK-8 or gastrin to the CCKB/gastrin receptor induced phosphoinositide breakdown and led to a rapid, transient, and concentration-dependent increase in intracellular Ca2+, which was completely blocked by a specific CCKB receptor antagonist. The peptides also stimulated tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin. Both CCK-8 and gastrin induced a dose- and time-dependent activation of MAP kinase and p74raf-1 kinase in the transfected Rat1 cells. These effects could be dissociated from protein kinase C activation and were not dependent on a functional Gi protein. Finally, both CCK-8 and gastrin induced DNA synthesis in Rat1 cells transfected with the human CCKB/gastrin receptor through a pertussis toxin-insensitive pathway. These results indicate that the neuropeptides gastrin and CCK can activate multiple signal transduction pathways and act as sole mitogens by binding to the CCKB/gastrin receptor transfected into Rat1 fibroblasts. PMID- 7794809 TI - Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration. AB - Liver regeneration after two-thirds partial hepatectomy (PH) is a process in which quiescent, fully differentiated hepatocytes rapidly reenter the cell cycle and eventually divide until the original liver mass is restored. Although the exact nature of the growth-initiating signals is unknown, enhanced expression of growth-related genes has been detected during the first hour after operation. This suggests that activation of transcriptional and posttranscriptional regulatory factors is likely to be a very early event in liver regeneration. Here we report the rapid, transient induction of DNA binding by nuclear factor (NF) kappa B (p50/p65 heterodimer) and p50 homodimers within 30 min after PH. We also detected binding of post-hepatectomy factor. NF-kappa B binding peaks at 1 h after PH before declining and is not induced by sham operation. Liver cell separation studies indicated that the binding activation occurs in hepatocytes, a conclusion further supported by cell culture studies using the hepatocyte cell line AML-12. Furthermore, studies with the liver epithelial cell line LE-6 indicated that these DNA-binding activities are mitogen inducible. One-third hepatectomy, a procedure which primes hepatocytes to respond to growth factors, also induced NF-kappa B binding. We also found that tumor necrosis factor alpha, which may be involved in the control of liver regeneration, rapidly induced NF kappa B DNA-binding activities in intact animals, similar to those induced by PH. These results suggest that NF-kappa B binding may play a role in making hepatocytes competent to proliferate. PMID- 7794808 TI - Localization of a cycloheximide-sensitivity response element in the human thymidine kinase gene promoter. AB - In order to localize the segment of the human thymidine kinase (TK) gene promoter that mediates sensitivity of TK mRNA expression to the presence of cycloheximide (CX), a series of promoter truncation mutants was prepared between the 460-base pair (bp) promoter that was demonstrated previously to be sensitive to CX and the 83-bp promoter that was demonstrated previously to be insensitive to CX. TK promoters containing 370, 300, 160, or 130 bp of 5'-flanking sequence were all sensitive to inhibition by CX. Further truncation to 100 bp of 5'-flanking sequence eliminated CX sensitivity. Electrophoretic mobility shift assays using a probe containing most of this region (but omitting the SP1 binding site at the 5' end of the 130-bp promoter) identified some complexes whose formation was sensitive to the presence of CX. Comparison of the sequences of oligonucleotides that were able to compete for formation of mobility shift complexes identified the sequence GCGGCC as a putative CX-sensitivity response element. Two such sequences are found between 83 and 130 bp 5' of the TK capsite. Mutation of the distal sequence attenuated sensitivity of TK mRNA expression to CX, while mutation of the proximal sequence had minimal effect on CX sensitivity. Thus, these data have localized a CX-sensitivity response element to a segment of TK promoter about 120 bp 5' of the capsite that includes the hexamer GCGGCC. PMID- 7794810 TI - Erythropoietin exerts transcriptional and translational control over globin synthesis in J2E cells. AB - The J2E erythroid cell line, generated by transforming fetal liver cells, terminally differentiates in response to erythropoietin (epo). The cells expressed both adult and embryonic globin genes, although considerably more adult globin was produced, and transcripts for both species rose following exposure to epo. A 6-fold increase in transcription of the adult alpha and beta maj globin genes was observed after hormonal stimulation, which resulted in a substantial accumulation of mRNA. In addition, a modest but transient rise in translation enabled a 6-fold elevation in globin protein to occur. Concurrently, the total heme content rose markedly, enhancing hemoglobin synthesis 10-fold. The prosthetic group complexed entirely with globin proteins, and the hemoglobin produced was present as fully functional oxyhemoglobin, capable of gaseous exchange. We concluded, therefore, that hemoglobin synthesis in epo-induced J2E cells normally results from the coordinate stimulation of heme and globin synthesis. However, some mutant clones emerged where concomitant increases in globin and heme were not observed. Despite similar profiles for the appearance of hemoglobin and equivalent amounts of the oxygen carrier, several noticeable differences in globin synthesis were detected between epo-induced J2E cells and DMSO-stimulated murine erythroleukemia cells, i.e., the types of globin genes expressed, patterns of mRNA and protein production, and translation rates. These results demonstrate that the J2E cells provide a useful model system for investigating the molecular mechanisms of epo-initiated hemoglobin synthesis. PMID- 7794813 TI - Phenotypic modification of human osteosarcoma cells with the phorbol ester 12-O tetradecanoylphorbol-13-acetate. AB - Treatment of the U-2 OS human osteosarcoma cell line with the phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) dramatically decreased the rate of DNA synthesis. This decrease in proliferation as well as the change in morphology of the TPA-treated cells can be blocked by the protein kinase C inhibitor GF 109203X. The U-2 OS cells are known to express the c-sis oncogene [platelet derived growth factor (PDGF) B-chain], PDGF-A, and receptors for PDGF, thus providing a potential autocrine loop of growth stimulation. TPA was found to induce the expression of both the PDGF-A and the PDGF-B chains. However, the levels of the PDGF receptor beta subunits and of the PDGF-BB inducable tyrosine phosphorylation of the PDGF receptor were markedly reduced. The TPA treatment of the U-2 OS cells also induced changes typical for maturing bone cells, such as increased expression levels of alkaline phosphatase and osteopontin. The expression levels of type I collagen and bone sialoprotein were reduced. The results show a TPA-dependent down-regulation of the PDGF receptor beta subunits that correlates with an increased expression of osteoblast phenotypic markers. PMID- 7794811 TI - Emergence of myeloid cells from cultures of J2E erythroid cells is linked with karyotypic abnormalities. AB - J2E cells are an erythroid cell line immortalized at the proerythroblast stage of differentiation by the J2 retrovirus which contains the raf and myc oncogenes. In response to erythropoietin, these cells terminally differentiate into mature, hemoglobin-producing erythroid cells. We have shown previously that B cells overexpressing raf and myc acquired the phenotype of macrophages, and here we demonstrate that, under adverse growth conditions, myeloid cells can also emerge from J2E cultures. Morphologically, ultrastructurally, and by cytochemical analyses, these cells resembled monocytic precursor cells at different stages of differentiation. They no longer responded to erythropoietin, failed to express an erythroid-specific surface antigen, and ceased producing transcripts for globin genes, GATA-1 and SCL. Most of the converted cells displayed surface antigens typically found on myeloid cells and in vivo produced histiocytomas with severe cachexia, instead of erythroleukemias. All of the myeloid convertants had karyotypic abnormalities, and we speculate that these mutations may have triggered the transition from erythroid to myeloid phenotype. Overexpression of raf and myc oncogenes may have generated genetic instability, which then influenced the commitment of cells to specific lineages. PMID- 7794814 TI - Expression of transforming growth factor beta ligand and receptor messenger RNAs in lung cancer cell lines. AB - Specific cDNA probes for transforming growth factor beta s (TGF-beta s) 1, 2, and 3 and TGF-beta types I, II, and III receptors were used to study expression of the mRNAs of the different TGF-beta ligand and TGF-beta receptor isoforms in cultured non-small cell lung cancer (NSCLC) cells and small cell lung cancer (SCLC) cells. Expression of TGF-beta 1 mRNA was detected in both cell types using Northern blot hybridization, with the level of expression of this mRNA being higher in several NSCLC cell lines. In addition, expression of TGF-beta 2 and TGF beta 3 mRNAs was also detected in NSCLC and SCLC cells but at levels that were lower than that of TGF-beta 1 mRNA. Besides expression of a 3.4-kilobase (kb) TGF beta 3 transcript, a smaller 2.8-kb TGF-beta 3 transcript was detected in some NSCLC and SCLC cells. TGF-beta 1 and TGF-beta 2 proteins were detected in the conditioned media of NSCLC and SCLC cells, with the levels being higher in several NSCLC cells than in SCLC cells. Expression of TGF-beta types I and II receptor mRNAs was also detected in most NSCLC and SCLC cells, with expression of a 5.5-kb type I receptor mRNA being higher than that of a 5.5-kb type II receptor mRNA in both cell types. In contrast, a 6-kb TGF-beta type III receptor mRNA was detected in only some NSCLC cells and could not be detected in the SCLC cells examined. Also, there was an inverse relationship between the level of expression of the 5.5-kb TGF-beta type I receptor mRNA and that of the 6-kb TGF-beta type III receptor mRNA. Addition of TGF-beta 1 and TGF-beta 2 proteins resulted in an increase in the mRNAs for TGF-beta s 1 and 2 and an increase in the amount of TGF beta 1 protein in some NSCLC cells, indicating that these cells are responsive to TGF-beta and its effects. At the same time, a differential change in expression of the 2.8- and 3.4-kb TGF-beta 3 transcripts was detected in some lung cancer cells following the addition of TGF-beta 1 and TGF-beta 2. Also, addition of TGF beta 1 to NSCLC cells inhibited colony formation of some of these cells in soft agarose in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7794815 TI - Presence of the two growth hormone receptor messenger RNA isoforms in human breast cancer. AB - In the present study, we have investigated specific growth hormone (GH) receptor gene expression in breast cancer cell lines and tissues. By Northern blot analysis, using a human GH receptor cDNA probe, the classically observed 4.7 kilobase GH receptor mRNA was evidenced in 2 of 29 cancer biopsies and in the MCF7 and T47-D cell lines. Reverse transcription coupled to PCR was used to amplify the GH receptor sequence encompassing a part of the extracellular domain as well as the transmembrane domain. An amplification product of the expected size (456 base pairs) was observed in 28 of 29 breast biopsies and in all the breast cancer cell lines studied (T47-D, MCF7, MDA-MB-231, and BT-20). The reverse transcription-PCR product was shown to be specific by Southern blot hybridization with the GH receptor cDNA probe and by specific cleavage of the amplified products with restriction enzymes. For the first time, the expression of GH receptor gene in breast cancer cell lines and biopsies is demonstrated in this study, suggesting a GH-specific action in tumor development. Additionally, the two isoforms of the human GH receptor (hGHR) mRNA, one containing exon 3 (hGHR-wt mRNA) and one excluding exon 3 (hGHR-d3 mRNA), were found to be expressed independently or simultaneously (29 tumors analyzed). The presence of hGHR-d3 mRNA appears to be patient specific, as demonstrated by comparing the expression pattern of both mRNAs between tumor biopsy and lymphocytes of the same patient. PMID- 7794812 TI - Human neuroblastoma I-type cells are malignant neural crest stem cells. AB - Human neuroblastoma I-type cells isolated from cell lines in vitro are morphologically intermediate between neuroblastic (N) cells, with properties of embryonic sympathoblasts, and substrate-adherent (S) cells having properties of embryonic Schwann/glial/melanocytic cells of the neural crest. I cells have biochemical features of both N and S cells. We propose that the I-type cell represents a malignant neural crest stem cell. The strongest evidence in support of this hypothesis is that: (a) I cells can generate progeny that have neuronal properties, i.e., are committed neuroblasts, or properties of nonneuronal, embryonic neural crest-derived cells; and (b) I-type cells can generate multipotent I-type progeny, indicating their capacity for self-renewal, a feature of stem cells. We report here that I-type cells, derived from four different human neuroblastoma cell lines and experimentally induced to differentiate, give rise to cells with distinct N or S cell phenotypes, indicative of I cell multipotentiality. Experiments with a large panel of I-type subclones, isolated from clonal I-type BE(2)-C cells and exposed to retinoic acid to induce neuronal differentiation or 5-bromo-2'-deoxyuridine to obtain S-type cells, demonstrated that differentiation occurs via induction and selection and not by selection of spontaneously arising variants. The differentiation phenotype was stable. We conclude that human neuroblastoma I-type cells are multipotent embryonic precursor cells of the peripheral nervous system, capable of either neuronal or nonneuronal neural crest cell differentiation. PMID- 7794816 TI - Nickel and skin irritants up-regulate tumor necrosis factor-alpha mRNA in keratinocytes by different but potentially synergistic mechanisms. AB - A critical role of tumor necrosis factor (TNF)-alpha in irritant contact dermatitis and in the challenge phase of allergic contact dermatitis has recently been demonstrated in vivo. As in situ hybridization studies have indicated that keratinocytes were the cellular source of TNF-alpha in these reactions, we studied the mechanisms of TNF-alpha mRNA induction in keratinocytes by agents that induce contact dermatitis. Murine la-/CD3- epidermal cells were stimulated with phorbol myristate acetate (PMA), dimethylsulfoxide (DMSO), sodium dodecyl sulfate (SDS) and NiSO4, all of which up-regulated epidermal cell TNF-alpha mRNA production. In contrast, trinitrobenzenesulfonic acid and trinitrochlorobenzene did not significantly up-regulate TNF-alpha mRNA. These results were confirmed with murine keratinocyte cell lines. In keratinocytes transfected with a chloramphenicol acetyltransferase construct containing the -1059 to +138 base pair TNF-alpha promoter, increased promoter activity was observed upon stimulation with PMA and DMSO. In addition, PMA stimulation did not affect the stability of TNF-alpha mRNA. The PMA- but also the DMSO- and SDS- induced up regulation of TNF-alpha mRNA was abolished by an inhibitor of protein kinase C (PKC). In contrast, NiSO4 up-regulated TNF-alpha mRNA by a PKC-independent mechanism, did not increase TNF-alpha promoter activity, but markedly increased the stability of the TNF-alpha mRNA. Co-stimulation with PMA and NiSO4 induced a marked increase in TNF-alpha mRNA over that obtained with each agent alone. Thus, whereas PKC-dependent irritants act by up-regulating TNF-alpha promoter activity, nickel acts via post-transcriptional regulation. Our results also establish that some irritants and irritant sensitizers directly induce TNF-alpha in keratinocytes without intermediate Langerhans cell-derived signals. PMID- 7794817 TI - The positively selected T cell repertoire: is it exclusively restricted to the selecting MHC? AB - Transgenic lines of mice showing compartmentalized expression of MHC I-E in different thymic microenvironments and nearly normal expression in the periphery were used to ask whether the mature T cell repertoire is restricted exclusively to the selecting MHC molecules expressed on thymic cortical epithelial cells. We show that upon in vivo priming, mice with a T cell repertoire selected in the thymic cortex on MHC I-A, in the absence of MHC I-E, display a clearly significant T cell response to two I-E-restricted peptides. Our results suggest that expression of one isotype or allele of class II MHC molecules in the appropriate thymic environment enables the selection of a polyclonal repertoire restricted in part to non-selecting class II MHC molecules. Thus, although the requirement for interaction with the MHC by the TCR on developing thymocytes exists, the available adult repertoire need not be solely faithful to the specific MHC expressed on the thymic cortical epithelium: it can also be restricted to other isotypes and alleles of this same class of MHC molecule. PMID- 7794818 TI - Assembly and intracellular transport of the human B cell antigen receptor complex. AB - The B cell antigen receptor (BCR) complex consists of transmembrane (m) Ig, in non-covalent association with a disulphide-linked heterodimer of mb-1 and B29 gene products. The MB-1-B29 heterodimer is required for deposition of the BCR at the plasma membrane, as well as for coupling of the antigen receptor to intracellular signal transduction cascades. We have performed biosynthetic labelling studies using the mature B cell line Ramos to investigate the process of assembly of the BCR components. We conclude that association of the four components, Ig-heavy chain (HC) and -light chain (LC), MB-1 and B29, is required and sufficient to permit exit of the BCR complex out of the endoplasmic reticulum (ER). With the short pulse labelling procedures used, no evidence was found for transient participation of other molecules in complex formation. A 32 kDa glycoprotein was identified, which is serologically related to MB-1, but has a more acidic isoelectric point (pl) and a protein backbone of 21 kDa, as compared with 25 kDa for MB-1. This protein did not appear to participate in BCR complex formation and is most likely degraded prior to reaching the cis-Golgi. The MB-1 component was found to be the rate-limiting step in BCR complex formation, while Ig-HC, -LC and B29 are synthesized in excess. Ig-HC and -LC form disulphide linked tetrameric complexes within 3 min after biosynthesis, with which B29 and MB-1 components associate independently, followed by disulphide bond formation between these heterodimeric partners. While partial BCR complexes containing B29 and mlg-H2L2 tetramers are rapidly formed and have a half-life of a few hours in the ER, entry of MB-1 into these complexes controls exit out of this compartment. PMID- 7794820 TI - IL-7 transgenic mice: analysis of the role of IL-7 in the differentiation of thymocytes in vivo and in vitro. AB - We have generated a high copy number transgenic mouse line in which expression of mouse IL-7 cDNA is under the control of the mouse MHC class II E alpha promoter. These mice were generated in order to see if IL-7 over-production in the thymus altered either thymocyte differentiation or the process of negative selection. Using in situ hybridization, IL-7 transcripts could be detected in the thymic cortex and medulla as well as the spleen and lymph nodes of transgenic mice but was undetectable in normal controls. Phenotypic and molecular analysis of thymocytes from embryonic and adult transgenic mice failed to reveal a dramatic effect of IL-7 on thymocyte differentiation and negative selection of the TCR V beta repertoire appeared to be intact. In peripheral lymph nodes, there was a massive (30-fold) increase in the number of T cells (CD8+ > CD4+) and simultaneous presence of immature (B220+, Ig-) B cells. TCR repertoire analysis showed that the expansion of peripheral T cells was polyclonal. Using the polymerase chain reaction (PCR), transgene-specific IL-7 transcripts could be detected in the thymus from day 14 of fetal development. However, using semi quantitative PCR, there was no dramatic increase in the degree of TCR beta or TCR alpha gene rearrangements during thymocyte ontogeny in vivo. Similarly, when fetal mouse thymus lobes were cultured with IL-7 in vitro, there was no dramatic increase in the degree of TCR beta or TCR alpha gene rearrangements. We conclude that IL-7 is probably not an important differentiation factor for immature mouse thymocytes. PMID- 7794819 TI - General role of HLA class I molecules in the protection of target cells from lysis by natural killer cells: evidence that the free heavy chains of class I molecules are not sufficient to mediate the protective effect. AB - Some HLA-C alleles have been shown to exert a specific protective effect preventing target cells from lysis by groups of natural killer (NK) clones displaying a defined specificity. In this study, we analyzed whether class I mediated protection is a more general phenomenon involving all NK cells. First, we utilized two anti-class I mAbs (6A4 of IgG1 isotype and A6-136 of IgM isotype), which had been shown to induce lysis of protected target cells by group 1 and group 2 NK clones. Addition of A6-136 or 6A4 used as F(ab')2 mAb resulted in lysis of protected target cells by all NK clones analyzed. Target cells were represented by a panel of HLA homozygous Epstein-Barr virus-transformed B cell lines (B-EBV) while NK clones were representative of clones displaying different GL183/EB6 surface phenotypes and/or different abilities to lyse allogeneic cells. Unselected NK clones derived from seven different individuals were tested against autologous target cells represented by phytohemagglutinin-induced blasts or B-EBV transformed cell lines. In both instances, addition of a mixture of 6A4 F(ab')2 and A6-136 mAbs resulted in lysis of autologous target cells, thus suggesting that class I molecules prevent lysis of normal cells by self NK cells. We further investigated whether the class I-mediated protection requires the complexed form of class I molecules (composed of alpha chain, beta 2-microglobulin and the antigen peptide) or rather the free alpha chain. Acidic treatment of the C1R (Cw4+) target cells or 81.22 (Cw3+, Cw4+) at pH 2.2 resulted in loss of reactivity with 6A4, A6-136 and W6-32 mAb (known to react with the assembled form of class I molecules) and in the de novo reactivity with L31 mAb (specific for the HLA-C free chain). While the untreated Cw+ C1R cells were resistant to lysis by the Cw4-specific group 1 NK clones, the pH 2.2-treated cells became highly susceptible to lysis by the same clones. These data indicate that, at least for the NK clones analyzed, the protection of target cells requires class I molecules in the complexed form. PMID- 7794821 TI - Lymphoproliferative disorders in IL-7 transgenic mice: expansion of immature B cells which retain macrophage potential. AB - Transgenic mice carrying the murine IL-7 gene under the MHC class II (E alpha) promoter are described which develop lymphoid tumours at a high incidence when maintained in conventional or specific pathogen-free environments. Cells obtained from the lesions were relatively monomorphic, expressed a variety of B cell associated markers (BP-1, B220, CD43) but lacked surface Ig. Some mice, showed expanded populations of cells phenotypically similar to the recently reported bipotent B/macrophage stem cell subset (AA4.1high, B220-, Ig-) which could be cloned and maintained in vitro. These cells expressed IL-7 receptors, proliferated in response to IL-7 and in most cases had germline configuration of the Ig heavy chain locus. Cell lines cloned from two such tumours generated macrophages spontaneously in culture, consistent with their bipotent B cell/macrophage phenotype. These results suggest that IL-7 plays a role in very early stages of B cell ontogeny prior to bona fide B cell commitment. PMID- 7794822 TI - Selective activation of VH3A10+ rheumatoid factor producing B cells by staphylococcal enterotoxin D. AB - Staphylococcal enterotoxin D (SED) is a T cell superantigen which selectively targets alpha beta TCRs bearing particular V beta elements. A second function of SED relates to the preferential activation of a B cell subset characterized by a high frequency of rheumatoid factor (RF) producing B cells. To define the molecular basis of the SED-induced B cell repertoire shift, we have analyzed Ig heavy chain genes in B cell clones expanded after SED stimulation and compared them with B cell clones established in the presence of anti-CD3 stimulated helper cells. Gene segments of the VH3 family were most frequently utilized under both stimulation conditions (42% anti-CD3; 47% SED). Sequence analysis of VH3 gene segments demonstrated that the repertoire of VH3 elements in B cell clones from SED driven and anti-CD3 driven cultures were distinct (P = 0.01). RF activity was closely associated with the expression of selected VH3 elements. B cell clones stimulated with SED preferentially expressed VH3A10, whereas VH26 was the gene segment dominantly used in B cell clones expanded with anti-CD3 stimulated helper cells. The usage of JH and DH elements was indistinguishable in SED and anti-CD3 driven B cell clones, suggesting that SED targets VH3+ B cells through a VH specific mechanism. Comparison of the closely related sequences of the SED responsive VH3A10 and the SED non-responsive VH26 element suggested a role of a sequence polymorphism in the CDR2 reminiscent of B cell reactivity to conventional antigens. In contrast to conventional antigens, SED can induce differentiation of a high frequency of naive B cells. Thus, this staphylococcal enterotoxin combines selective activation of T cells with selective activation of B cells and might be able to direct T cell help to RF producing B cells. PMID- 7794824 TI - Differential sensitivity to transforming growth factor (TGF)-beta of CBA and of CBA/N B cells demonstrates that the IgG2b inducing factor in synovial fluid from rheumatoid arthritis patients is not identical to TGF-beta. AB - Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains in vivo produced cytokines and inflammatory mediators, including a factor that induces IgG2b production of lipopolysaccharide (LPS) preactivated murine B lymphocytes. In order to determine the mechanism by which RA-SF acts on LPS activated mouse B cells, CBA/N mice were used as an experimental model. The X-linked immunodeficiency of these mice is caused by a point mutation in the Bruton's tyrosine kinase (btk) gene. We have earlier shown that RA-SF can reconstitute the CBA/N B cell deficiency in vitro and in vivo, with regard to IgG2b production after LPS stimulation. Since transforming growth factor (TGF)-beta has been suggested to be a switch factor for IgG2b, we aimed at investigating the role of TGF-beta in our experimental system. We found that TGF-beta could not mimic the effect of RA-SF on CBA spleen cells. A small increase of IgG2b secretion was observed with spleen cells from normal CBA mice, whereas Ig secretion of all isotypes was suppressed in CBA/N spleen cells treated with TGF-beta at any concentration. Neutralizing antibodies against TGF-beta suppressed the response of CBA B cells, whereas the response by CBA/N B cells was enhanced by the same antibody preparation. Here we also show that the abnormal B cell responsiveness to TGF-beta, typical of CBA/N, co-segregates with the btk mutation in male (CBA x CBA/N)F2 spleen cells. This was determined by allele specific PCR recognizing the identified base substitutions of the btk gene, typical of the two strains. We propose that RA-SF contains a factor, separate from TGF-beta, that is involved in the differentiation of IgG2b expressing cells. PMID- 7794825 TI - TCR repertoire in early fetal mouse thymus. AB - We investigated the rearrangement and expression of TCR genes in mouse fetal thymus organ culture, a system that avoids subsequent entry of hematopoietic precursor cells. The first observable rearranged TCR gene was homogeneous V gamma 2-J gamma 2, detectable as early as fetal day 11 (d11) in the thymic primordia. The productive TCR was homogeneous V gamma 5-J gamma 1, first detectable in d13 thymocytes, followed by adult-type TCR gamma (V gamma 4 and V gamma 7). Sequence analysis of TCR revealed five types of V-J junctional sequences. In the very early stage, a homogeneous V-J junction is generated via a short homology sequence in the coding region (Type I), while a short homology sequence in the P nucleotide rather than the coding region is used in the following stage (Type II). In the later embryonic stages, diverse V-J junctions are generated by well known mechanisms, such as P-nucleotide (Type III), N-region insertion (Type IV) or trimming of the coding ends (Type V). These findings suggest that the generation of homogeneous TCR gamma (V gamma 2 and V gamma 5) in the early fetal stages is due to the intrinsic rearrangement mechanisms and is in stage specific manner. PMID- 7794823 TI - Over-expression of CD3 epsilon transgenes blocks T lymphocyte development. AB - We have reported previously that mice carrying > 30 copies of the human CD3 epsilon transgene completely lose their T lymphocytes and NK cells (36). Here we demonstrate by immunohistology that in the most severely immunodeficient mouse, tg epsilon 26, the thymus is very small, has sizeable vacuoles and does not contain recognizable T lymphocytes except for a small percentage of Thy-1+ cells and B cells. Cell surface phenotyping and TCR alpha and -beta rearrangement studies confirm that the arrest in T lymphocyte development precedes the arrest in rag-1null, rag-2null and TCR beta nuli mice. Since the T cell progenitors in which the arrest occurred were absent in the transgenic mice, indirect approaches were taken to examine the causes of the block in T cell development. Analyses of 12 independently established mutant mouse lines, generated with five different transgenic constructs, revealed that the severity of the abrogation in T cell development was dependent on the number of copies of transgenes. Since the number of transgene copies generally correlated with the levels of expression of the transgenic CD3 epsilon proteins, we concluded that over-expression of the CD3 epsilon protein was the likely cause of the block in T lymphocyte development. The T cell immunodeficiency was caused by either the human or the murine CD3 epsilon protein. Since transgene coded mRNAs were found in significantly higher quantities than endogenous CD3 epsilon mRNAs in fetal thymi on days 13 and 14 of gestation, over-expression took place very early in development, probably prematurely. Over-expression of the CD3 epsilon transgene in thymocyte precursors may therefore affect T lymphocyte development in the absence of TCR and possibly in the absence of the other CD3 proteins. More importantly, over-expression of the CD3 epsilon protein in thymocytes of mice with a low copy number of transgenes had a significant effect on late thymic development. Over-expression of the CD3 epsilon protein in immature thymocytes mimicked the effects caused by exposure of CD4- CD8- thymocytes to anti-CD3 epsilon treatment: apoptosis and lack of TCR beta expression. We therefore speculate that in the homozygous tg epsilon 26 animals the arrest in T cell development was caused by excessive signal transduction events rather than by a toxic effect of the transgenic protein. PMID- 7794827 TI - Visualizing properties of atomic and molecular systems. AB - In this article scientific visualization techniques that allow for the interactive computation and display of molecular structures and properties are presented. The electronic properties are computed and displayed using the application visualization system (AVS). By combining the visualization techniques of AVS with an orbital description of molecular systems, a better understanding of the electronic behavior of the systems can be achieved. Molecular properties such as the electrostatic potential and chemical reactivity index (the Fukui function) are computed and mapped onto isodensity displays of the electron density of the system. PMID- 7794826 TI - CD4+ but not CD8+ T cells are required for the induction of oral tolerance. AB - It has been suggested that oral tolerance is mediated by CD8+ T lymphocytes, but the functional properties of these cells are unclear. Here we show that the induction of tolerance by feeding mice ovalbumin (OVA) does not prime antigen specific class I MHC-restricted cytotoxic T cells in vivo. Indeed, such responses are markedly suppressed in mice fed OVA, and the induction of oral tolerance is abolished by depletion in vivo of CD4+ but not CD8+ T cells. These results indicate that CD8+ lymphocytes are unlikely to play a major role in the induction of oral tolerance and are the first demonstration that specific cytotoxic responses to an exogenous antigen can be suppressed by feeding antigen. PMID- 7794828 TI - Development of quantitative structure property relationships for poly(arylene ether)s. AB - The technique of quantitative structure-activity relationships (QSAR) is well accepted by the drug design community. The analogous technique of quantitative structure-property relationships (QSPR) has applications in the field of polymer chemistry. A variety of molecular modeling and molecular orbital techniques was used to find molecular descriptors that could be used to derive an empirical equation to describe the glass transition temperature of two related classes of poly(arylene ether)s. The derived equation was then used to predict the thermal characteristics of another polymer of the same type. PMID- 7794829 TI - EXTRACT: a program to extract three-dimensional coordinates from stereo diagrams of proteins. AB - The program EXTRACT has been developed to extract accurate three-dimensional coordinates from published stereo alpha-carbon diagrams of protein structures. The approach is based on the display of scanned images of the left and right eye views of the diagram on a stereo-equipped workstation, allowing construction of a molecular model using the diagram as a guide. A number of structural checks assess the building, including probability maps derived for alpha-carbon geometry in protein structures. The procedure has also been extended to produce less accurate models from mono images. PMID- 7794830 TI - GAME: a computer graphics method for calculating and displaying the molecular electrostatic potential. AB - A new method for calculating and displaying the molecular electrostatic potential on the molecular surface is described. The main advantage of the method, besides some others, is its consistency. This means one only needs one data set for the surface and the MEP: a 3D field of the electron density from any source. PMID- 7794832 TI - Modeling cation/anion-water interactions in functional aluminosilicate structures. AB - A need for the computer simulation of hydration/dehydration processes in functional aluminosilicate structures has been noted. Full and realistic simulations of these systems can be somewhat ambitious and require the aid of interactive computer graphics to identify key structural/chemical units, both in the devising of suitable water-ion simulation potentials and in the analysis of hydrogen-bonding schemes in the subsequent simulation studies. In this article, the former is demonstrated by the assembling of a range of essential water-ion potentials. These span the range of formal charges from +4e to -2e, and are evaluated in the context of three types of structure: a porous zeolite, calcium silicate cement, and layered clay. As an example of the latter, the computer graphics output from Monte Carlo computer simulation studies of hydration/dehydration in calcium-zeolite A is presented. PMID- 7794831 TI - Self-organizing maps and molecular similarity. AB - Self-organizing maps generated by Kohonen neural networks provide a method for transforming multidimensional problems into lower dimensional problems. Here, a Kohonen network is used to generate two-dimensional representations of the electrostatic potential about the ring structures of histamine H2 agonists. Previous work by J. Gasteiger and X. Li (Angew. Chem. Int. Ed. Engl. 1994, 33, 643) has shown the usefulness of such a method for classifying molecules as muscarinic or nicotinic agonists. Here, the method is extended to rank histamine H2 agonists in order of biological activity. PMID- 7794833 TI - An algorithm for smoothly tessellating beta-sheet structures in proteins. AB - An algorithm is presented for tiling the surface of beta-sheet structures, smoothed both along the strands and perpendicular to them. The algorithm is intended for creating graphical representations of beta structure within the three-dimensional context of proteins. This article presents sufficient detail to allow a programmer with some knowledge of protein structure to implement the tiling algorithm. Several examples of its use are illustrated. PMID- 7794834 TI - Use of TSAR as a new tool to analyze the molecular dynamics trajectories of proteins. AB - There is a lack of tools to analyze simulations of protein molecular dynamics quantitatively. Our aim is to use calmodulin, a prototypical calcium-binding protein, to describe a strategy and some tools for extracting relevant information from dynamics calculations. Our main conclusions are as follows: Autocorrelation vectors may be used to represent a 3D conformation in an n dimensional space, where n is variable (n < or = 20-30). On such a transformation, classic statistical tools (PCA, clustering, etc.) may be used to differentiate or characterize dynamics trajectories quantitatively. TSAR, an integrated package used for quantitative structure-activity relationships, is well suited (after minor modifications) for such a purpose. Finally, this type of strategy is able to point out the effects of the solvent screening parameters of the Amber software on the dynamics trajectories of calmodulin. PMID- 7794836 TI - XmMol: an X11 and motif program for macromolecular visualization and modeling. AB - XmMol is a desktop tool designed to provide both interactive molecular graphics on X11 displays and easy interface with external applications. A kernel provides an interactive wire-frame display of macromolecules. It supports depth cueing, 3D clipping, and stereo. Various representations, coloring, and labeling modes are proposed. Docking and interactive backbone deformation tools are also supported. Communication protocols allow the user to develop new external features or to use XmMol as a visualization tool for external numerical programs. PMID- 7794838 TI - The implications of the changing nature of gynaecological surgical practice on training. PMID- 7794835 TI - QMView: a computational chemistry three-dimensional visualization tool at the interface between molecules and mankind. AB - QMView is designed to facilitate the visualization and interpretation of quantum mechanical data. Capabilities include display of chemical structure, animation of quantum mechanically determined vibrational modes, and depiction of electronic properties and three-dimensional molecular orbitals. QMView has a user-friendly interface that allows users to interactively manipulate many features of the molecular structure and/or property, including positioning and structure representation, via mouse-activated dialog boxes. Although the interface allows input from results of any of the popularly used quantum mechanical software, we have focused on GAMESS, a widely distributed quantum chemistry code. QMView has been designed with the special feature of working in distributed mode with GAMESS, the latter running on a supercomputer, the former running on a Silicon Graphics platform. Ancillary programs provide a method of obtaining output of graphic images in various media, including hardcopy, PostScript files, slide, and/or video. These and other original features discussed in this article provide a graphic interface that is unique compared to others that are currently available. Examples of images produced by QMView are presented. PMID- 7794837 TI - VISTAS: a package for VIsualizing STructures and sequences of proteins. AB - VISTAS is a suite of programs for protein sequence and structure analysis. The system allows the simultaneous display, in separate windows, of multiple sequence alignments, of known or model 3D structures, and of 2D graphic representations of sequence and/or alignment properties. The displays are fully integrated, and therefore manipulations in one window can be reflected in each of the others. Beyond its display facilities, VISTAS brings together a number of existing tools under a single, user-friendly umbrella: these include a fully functional interactive color alignment procedure, conserved motif selection, a range of database-scanning routines, and interactive access to the OWL composite sequence database and to the PRINTS protein fingerprint database. Exploration of the sequence database is thus straightforward, and predefined structural motifs from the fingerprint database may be readily visualized. Of particular note is the ability to calculate conservation criteria from sequence alignments and to display the information in a 3D context: this renders VISTAS a powerful tool for aiding mutagenesis studies and for facilitating refinement of molecular models. PMID- 7794839 TI - Prolactinomas: present day management. PMID- 7794841 TI - Caesarean operations performed in Edinburgh during the 18th century. PMID- 7794840 TI - Should perinatal post mortems be carried out by specialist pathologists? PMID- 7794842 TI - Blood pressure changes during labour and whilst ambulating with combined spinal epidural analgesia. AB - OBJECTIVE: To determine the influence of combined spinal epidural analgesia with fentanyl and low dose bupivacaine on maternal blood pressure and pulse rate in labour. Also, to evaluate the maternal cardiovascular response to mobilising with this form of analgesia in labour. Finally, to define the changes that occur in blood pressure and pulse rate during the second stage of labour and immediately postpartum when using combined spinal epidural analgesia. DESIGN: A prospective observational study. SUBJECTS AND METHODS: Blood pressure and pulse measurements were made at least every 10 minutes, using the SpaceLabs 90207 ambulatory blood pressure monitor, on 62 women in labour with combined spinal epidural analgesia. RESULTS: A significant fall in systolic blood pressure (> 20%) occurred in eight women (12%), all within 30 minutes of the spinal injection. Fifty-two women subsequently received an epidural dose (mean interval 90 minutes after spinal) and none of these women had a fall in systolic blood pressure of greater than 20%. No women had symptoms related to hypotension. Thirty-five women ambulated for more than 10 minutes on 65 occasions. Average blood pressure remained unchanged while ambulating (126/79 versus 126/79), but pulse rate was significantly increased (85 to 90, P < or = 0.001). The mean blood pressure in the second stage of labour (n = 41) did not rise with pushing (134/83 versus 134/83), but the pulse rate increased significantly (94 to 108, P < or = 0.001). Blood pressure remained unchanged immediately postpartum (n = 33) (134/83 versus 134/81) following ergometrine administration. CONCLUSION: The combined spinal epidural analgesia will only result in significant falls in systolic blood pressure within 30 minutes of the spinal injection. No further important changes in blood pressure occur when mobilising or with epidural top-ups. The combined spinal epidural analgesia may modify the normal compensatory mechanisms of blood pressure control, but does not cause significant maternal hypotension once the spinal injection has been given. PMID- 7794843 TI - Standing at work and preterm delivery. AB - OBJECTIVE: Guidelines in some European countries and the United States suggest that pregnant women should avoid prolonged standing and heavy lifting in the workplace during the second and third trimester of pregnancy. However, results from epidemiological studies on this topic are ambiguous. The aim of this study was to evaluate the influence of standing and walking at work in the second trimester on preterm delivery in a population with a low frequency of other workplace hazards. SUBJECTS AND DESIGN: A prospective cohort of 8711 women with singleton pregnancies was established during 1989 through 1991. Information was collected during the 16th week of pregnancy about medical and obstetrical history, general lifestyle factors and exposures at work. The analyses were restricted to 4259 respondents who worked at the 16th week. Potential confounders and effect modifiers were evaluated by stratification and multivariate analyses. RESULTS: After adjustment for confounders, women standing more than five hours per work day had an odds ratio (OR) for preterm delivery of 1.2 (95% CI 0.6 to 2.4) compared with women standing two hours or less. For walking, the OR was 1.4 (95% CI 0.7 to 2.5). Many women were unable to separate periods of standing from periods of walking; a combined measure of these two exposures was created to reflect exposure intensity. Women who reported more than five hours of both standing and walking had an adjusted OR of 3.3 (95% CI 1.4 to 8.0) compared with women who reported two hours or less on either of the exposures. No adverse effects were seen for lifting or other types of physical exertion. CONCLUSIONS: Our findings suggest that standing and walking at work during the second trimester may present a particular risk for preterm delivery, and workplace guidelines are justified. Further research is needed to address the specific mechanisms by which physical exertion, including standing and walking, might cause preterm delivery. PMID- 7794845 TI - The influence of maternal haemoglobin and ferritin on mid-pregnancy placental volume. AB - OBJECTIVE: To investigate whether low maternal haemoglobin and ferritin levels are associated with increased placental volume by mid-pregnancy. DESIGN: Prospective study of women attending hospital for shared antenatal care. SETTING: A teaching hospital in the south of England. SUBJECTS: Five hundred and sixty eight women booking for delivery in the hospital. MAIN OUTCOME MEASURES: Placental volume measured by ultrasound at 18 weeks gestation. RESULTS: At 14 weeks gestation 9% of women had haemoglobin levels < or = 11 g/dl and 26% had ferritin levels < 13 micrograms/l. Placental volume at 18 weeks was inversely related to the maternal haemoglobin and ferritin levels. The influence of haemoglobin and ferritin concentrations was independent of maternal social class, parity, smoking, and weight. Larger placentae were found in taller women, those who had previously been pregnant, and in those who were smoking more than 15 cigarettes daily at the time of their last menstrual period. CONCLUSION: These data suggest that placental development is influenced from early in pregnancy by the intrauterine environment provided by the mother. In conjunction with other studies they support the proposal that, as a result of these changes, programming of adult blood pressure may be initiated in early pregnancy. PMID- 7794844 TI - Fetal fibronectin detection for prediction of preterm birth in low risk women. AB - OBJECTIVE: To evaluate the clinical value of cervical fetal fibronectin detection by a quantitative enzyme-linked immunosorbent assay (ELISA) (PTDcheck, Adeza Biomedical, Sunnyvale, California, USA) as a screening tool for the prediction of preterm contractions and preterm delivery in an unselected population of pregnant women globally considered to be at low risk for preterm delivery (n = 133). DESIGN: A prospective study in which cervical fetal fibronectin samples were collected at two-week intervals between 26 and 36 weeks of gestation. SETTING: A regional training hospital. SUBJECTS: One hundred and thirty-three singleton pregnancies presenting consecutively at an antenatal clinic. MAIN OUTCOME MEASURE: Occurrence of preterm contractions and preterm delivery (delivery at < 37 weeks of gestation). RESULTS: Twenty-four (18%) patients were considered positive for the presence of fetal fibronectin. Overall 15 patients (11%) developed preterm contractions and, despite therapeutic intervention, 10 patients (8%) were delivered preterm. As a predictor for preterm contractions, cervical fetal fibronectin detection had a sensitivity of 47%, a specificity of 86%, a positive predictive value of 29% and a negative predictive value of 93%. As a predictor for preterm delivery, cervical fetal fibronectin detection had a sensitivity of 60%, a specificity of 85% a positive predictive value of 25% and a negative predictive value of 96%. CONCLUSIONS: Cervical fetal fibronectin determinations at a two-week sampling frequency for prediction of preterm birth in a general obstetric population at low risk for preterm birth has limited clinical value as a routinely performed screening procedure. PMID- 7794848 TI - Obstetricians' views on prenatal diagnosis and termination of pregnancy: 1980 compared with 1993. AB - OBJECTIVE: To examine the attitudes of obstetricians in England and Wales concerning prenatal diagnosis and termination of pregnancy and to compare these with a similar survey carried out in 1980. METHODS: Postal questionnaires, based on those used in 1980, were sent to a random sample of 555 nonacademic consultant obstetricians, 71% of whom replied. RESULTS: The proportion of consultant obstetricians with a conscientious objection to termination of pregnancy was the same in both surveys, although virtually all conscientious objectors said that they made an exception for serious fetal abnormality. A major change was in the proportion saying that they generally required an undertaking to terminate an affected pregnancy before proceeding with amniocentesis: 75% in 1980 compared with 34% in 1993. As in 1980, lower priority is given to telling women of negative test results than of positive. More obstetricians in 1993 are prepared to consider terminations later in pregnancy, both for fetal abnormality and for social reasons, than was the case in 1980, but many are not prepared to recommend termination as late in pregnancy as the law allows. In some cases this is due to misapprehensions about what is legal. There are particular problems concerning terminations for fetal anomalies that not all would consider serious. One in seven of the 1993 sample would not recommend termination for cystic fibrosis at any gestation. Only 13% would recommend termination for Down's syndrome beyond 24 weeks. There is a need not only for clarification of the law, but also of obstetrician's willingness to implement it. PMID- 7794847 TI - Does early growth delay occur in diabetic pregnancy? AB - OBJECTIVE: To identify the date of ovulation in pregnant women with Type 1 diabetes in order to assess the validity of the concept of early growth delay. DESIGN: Identification of ovulation by measurement of urinary luteinising hormone and assessment of fetal growth using ultrasound scan. SETTING: Diabetic pre pregnancy and antenatal clinic in a teaching hospital. SUBJECTS: Twenty women with Type 1 diabetes who had attended a pre-pregnancy clinic. MEASURES: Urinary LH, by laboratory and kit methods, during conception cycles. Human chorionic gonadotrophin measured in early pregnancy. Early ultrasound scans by a single observer blind to menstrual and ovulation dates. OUTCOME: Gestation calculated from ovulation date and gestation estimated from menstrual dates, compared with gestation at age indicated by early ultrasound scan. RESULTS: When the date of ovulation was identified in 20 women with Type 1 diabetes there was no evidence of growth delay in any pregnancy. When gestation was estimated from menstrual dates there was apparent early growth delay in six pregnancies. CONCLUSION: This study, together with others discussed, indicates that early growth delay is probably an artefact of incorrectly estimated ovulation date. PMID- 7794846 TI - First trimester amnifiltration: technical, cytogenetic and pregnancy outcome of 104 consecutive procedures. AB - OBJECTIVE: To investigate the technical, cytogenetic and pregnancy complications of first trimester amnifiltration for the diagnosis of fetal karyotype. DESIGN: Observational study. SETTING: The fetal medicine unit, UMDS St Thomas' Campus, London. SUBJECTS: One hundred and four women seeking prenatal diagnosis of fetal karyotype. MAIN OUTCOME MEASURES: Sampling success, culture rate, harvest time and karyotype, pregnancy outcome and complications. RESULTS: Sampling was successful in all 104 cases, but equipment failure forced the procedure to be changed to early amniocentesis in eight (7%) cases. The karyotype was normal in 101 (97%) cases, abnormal in three. The mean harvest time was 14 days (range 9-26 days; SD = 3.4), and three cultures failed (2.8%). Pregnancies resulted in 99 (95%) live births, with a mean gestation of 277 days (range 182-300 days; SD = 16). There was one termination for trisomy 21 and four spontaneous miscarriages (3.8%). Amniotic fluid leakage occurred in six cases (5%), all resulted in live births, five at term and one at 35 weeks. CONCLUSIONS: This study demonstrates that amnifiltration is technically possible in the first trimester of pregnancy, and that samples can be successfully karyotyped. The harvest time for culture is similar to early amniocentesis and chorion villus sampling. The rate of fetal loss, adjusted by the estimated natural loss, is 1.7%, which compares favourably with both chorionic villus sampling and early amniocentesis. PMID- 7794849 TI - Measurement of creatine kinase activity and diagnosis of ectopic pregnancy. AB - OBJECTIVE: To investigate whether the measurement of maternal plasma creatine kinase concentration is of clinical value in the diagnosis of tubal ectopic pregnancy. DESIGN: A retrospective observational study covering a three month period. SETTING: The gynaecological emergency service of a UK teaching hospital. SUBJECTS: One hundred and twenty women presenting with clinical suspicion of an ectopic pregnancy such that plasma human chorionic gonadotrophin (hCG) concentration was measured. MAIN OUTCOME MEASURES: Plasma hCG and creatine kinase concentrations were measured. Pregnancies were classified as ectopic pregnancy, complete miscarriage, incomplete miscarriage or ongoing pregnancy. Pregnancies were further classified as uncertain diagnosis if the diagnosis was not clear after initial investigation. RESULTS: Twenty-one of the patients had an ectopic pregnancy. Diagnosis was classified as uncertain in 48% of pregnancies studied and in 54% of ectopic pregnancies during the study period. The mean plasma creatine kinase was higher in ectopic pregnancies than other pregnancies in the study group (P < 0.01) and remained higher in the subgroup of patients with uncertain diagnosis (P < 0.05) but there were significant overlaps in creatine kinase concentrations in all four clinical groups. When a cut-off point of 45 iu/l is used, the measurement of plasma creatine kinase activity has a sensitivity of 0.57 and a specificity of 0.67 for the diagnosis of ectopic pregnancy. PMID- 7794850 TI - Increase in bone mass of older postmenopausal women with low mineral bone density after one year of percutaneous oestradiol implants. AB - OBJECTIVE: To evaluate the effect of 75 mg oestradiol implants on the bone mass of older postmenopausal women with osteoporosis. DESIGN: One year prospective controlled study. SUBJECTS: Thirty-two postmenopausal women over 60 years of age and more than five years postmenopausal with low bone density were recruited. Thirty women completed treatment for one year with 75 mg oestradiol implants. The changes in bone density were compared with a control group of 14 women. The side effects with treatment were documented. MAIN OUTCOME MEASURES: Dual energy X-ray absorptiometry of the lumbar spine and proximal femur using Hologic 1000 QDR before treatment and at one year. Plasma oestradiol assays were performed before and after one year. RESULTS: The median percentage changes in the treated group after one year was 12.6% at the lumbar spine and 5.22% at the total hip. The increase in vertebral bone density was greatest in women with low initial bone density (r = -0.35, P < 0.05) and those with highest treatment plasma oestradiol levels (r = 0.47, P < 0.01). Side effects were common but most were transient and mild in nature. CONCLUSION: 75 mg oestradiol implants significantly increase the bone mineral density at the spine and hip of older postmenopausal women with established osteoporosis. PMID- 7794851 TI - A dose-ranging study of the use of cyclical dydrogesterone with continuous 17 beta oestradiol. AB - OBJECTIVE: To establish the lowest dose of cyclical dydrogesterone that protects against endometrial hyperplasia induced by continuous 2 mg 17 beta oestradiol, and to study the dose effect on vaginal bleeding and side effects. DESIGN: Double blind, prospectively randomised dose-ranging study. SETTING: Menopause clinics in the UK and The Netherlands. SUBJECTS: Three hundred and seventy-one postmenopausal women with intact uteri, aged 40 to 60. INTERVENTIONS: Administration of six 28-day treatment cycles of continuous daily micronised 17 beta oestradiol with a randomly allocated dose of 5 to 20 mg of dydrogesterone added for the last 14 days of each. MAIN OUTCOME MEASURES: Histological assessment of adequate progestational endometrial response, bleeding patterns and adverse effects. RESULTS: The study was completed by 320 subjects (86%). Endometrial transformation occurred in over 94% of those taking 5 mg of dydrogesterone, and in over 97% of those on higher doses, without significant differences between the 10, 15 and 20 mg groups. Acceptable bleeding patterns were found at all doses, with the incidence of withdrawal bleeding rising with increasing dose. The day of onset of bleeding was predictable from cycle to cycle, and occurred later in the 20 mg group than in the others. The incidence of noncyclic bleeding was about 6% at all doses. Withdrawal occurred in 3.3% due to unacceptable bleeding and in 5.4% due to side effects. There was no relation with dose. CONCLUSIONS: A dydrogesterone-17 beta oestradiol combination hormone replacement therapy confers endometrial protection with an acceptable bleeding pattern and few side effects At least 10 mg of dydrogesterone for 14 days is required for acceptable endometrial protection. PMID- 7794852 TI - A Scottish audit of hysteroscopic surgery for menorrhagia: complications and follow up. Scottish Hysteroscopy Audit Group. AB - OBJECTIVE: To evaluate the efficacy and safety of hysteroscopic surgery undertaken by a cross section of gynaecologists. DESIGN: A prospective registration of cases of hysteroscopic surgery by gynaecologists. Patient satisfaction was assessed at six and twelve months post-operatively by postal questionnaire. SETTING: Thirteen hospitals in seven Scottish Health Boards. Secretariat in Aberdeen Royal Infirmary. SUBJECTS: Women having hysteroscopic surgery for menstrual problems. INTERVENTIONS: A few questions were added to the proforma during the audit. RESULTS: Between December 1991 and December 1993, 978 cases were registered. Consultants performed the majority of procedures. Complications occurred in 12% of cases and included one death from toxic shock syndrome. Uterine perforation and significant fluid overload occurred in 1% of cases. To date, 732 women have been followed up at six months, 554 at twelve months and 80 at 24 months. Eighty-four percent of those returning their questionnaires were satisfied or very satisfied at twelve months. By twelve months, repeat procedures had been performed in 13% and hysterectomy in 11%. Sixty-six percent of women with a paid job had returned to work within two weeks and 88% within four weeks. CONCLUSIONS: Overall, hysteroscopic surgery had a low rate of morbidity and satisfactory efficacy with rapid post-operative recovery. Gynaecologists who have shown caution with the advent of this surgery can now be encouraged to take up endometrial ablation for dysfunctional uterine bleeding. Clinical guidelines are currently being prepared. PMID- 7794854 TI - The value of histopathological examination of conceptual products. PMID- 7794853 TI - Duplex ultrasound screening for deep venous thrombosis in the puerperium. PMID- 7794855 TI - Focal salmonellosis: an unusual presentation of uterine malignancy. PMID- 7794856 TI - Mouth-operated mucus extractors: safe to use? PMID- 7794857 TI - Planned vaginal delivery after two previous caesarean sections. PMID- 7794858 TI - Magnesium sulphate for pre-eclampsia and eclampsia: the evidence so far. PMID- 7794859 TI - Conserving the cervix at hysterectomy. PMID- 7794861 TI - Definition of pre-eclampsia. PMID- 7794860 TI - Definition of pre-eclampsia. PMID- 7794862 TI - Cancer associated human papillomavirus perinatal transmission and persistence. PMID- 7794863 TI - Failure to progress in the management of labour. PMID- 7794864 TI - A multicentre randomised trial of amniotomy in spontaneous first labour at term. PMID- 7794865 TI - A multicentre randomized trial of amniotomy in spontaneous labour at term. PMID- 7794866 TI - Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised trial. PMID- 7794867 TI - The role of the large intestine in post-ruminal digestion of feeds as measured by the mobile-bag method in cattle. AB - To study the importance of site of recovery and other factors related to mobile bag (MB) digestion values, two consecutive experiments in which diets were applied in a 3 x 3 Latin square design, were carried out with cannulated growing heifers. In Expt 1, several types of experimental feed were exposed to intestinal digestion in mobile bags made of two cloth types and filled with intact or rumen undegradable (RUD) feed material to be recovered either from the ileum (IB) or faeces (FB). In Expt 2, mean retention time (MRT) of Yb-labelled digesta particles within the intestine and in vivo digestibility of diets were measured. With vegetable concentrates, FB resulted generally in slight overestimation of small-intestinal dry matter and N digestion, while with meat-and-bone meal no difference between FB and IB was found. The respective N digestibility of RUD late-cut silage was clearly underestimated as measured from FB. The disappearance of neutral-detergent fibre (NDF) of all feeds under test was higher from FB than from IB. It was not possible to isolate the influence of the large intestine on the MB values by changing bag cloth type. Irrespective of the longer retention time of bags and longer MRT of Yb in the intestine on a low as compared with a high level of feeding, only NDF disappearance of feeds increased due to lower feeding level. Altering the diet type to increase large-intestinal fermentation, as indicated in vivo, usually had no effect on the MB values. It is concluded that the site of collection of bags does not practically affect small-intestinal digestion values of feed N, unless the feed is rich in fibre. PMID- 7794868 TI - Body mass index: a measure of fatness or leanness? AB - The relationship between body fat and stature-adjusted weight indices was explored. Assuming the term height2 is a valid indicator of a subject's lean body mass, height2/weight was shown to be an accurate measure of percentage lean body mass and, as such, a better predictor of percentage body fat than the traditional body mass index (BMI; weight/height2). The name, lean body mass index (LBMI), is proposed for the index height2/weight. These assumptions were confirmed empirically using the results from the Allied Dunbar National Fitness Survey (ADNFS). Using simple allometric modelling, the term heightp explained 74% of the variance in lean body mass compared with less than 40% in body weight. For the majority of ADNFS subjects the fitted exponent from both analyses was approximately p = 2, the only exception being the female subjects aged 55 years and over, where the exponent was found to be significantly less than 2. Using estimates of percentage body fat as the dependent variable, regression analysis was able to confirm that LBMI was empirically, as well as theoretically, superior to the traditional BMI. Finally, when the distributional properties of the two indices were compared, BMI was positively skewed and hence deviated considerably from a normal distribution. In contrast, LBMI was found to be both symmetric and normally distributed. When height and weight are recorded in centimetres and kilograms respectively, the suggested working normal range for LBMI is 300-500 with the median at 400. PMID- 7794869 TI - The reproducibility of subjective appetite scores. AB - Although subjective appetite scores are widely used, studies on the reproducibility of this method are scarce. In the present study nine healthy, normal weight, young men recorded their subjective appetite sensations before and during 5 h after two different test meals A and B. The subjects tested each meal twice and in randomized order. Visual analogue scale (VAS) scores, 10 cm in length, were used to assess hunger, satiety, fullness, prospective food consumption and palatability of the meals. Plasma glucose and lactate concentrations were determined concomitantly. The repeatability was investigated for fasting values, delta-mean 5 h and mean 5 h values, delta-peak/nadir and peak/nadir values. Although the profiles of the postprandial responses were similar, the coefficients of repeatability (CR = 2SD) on the mean differences were large, ranging from 2.86 to 5.24 cm for fasting scores, 1.36 to 1.88 cm for mean scores, 2.98 to 5.42 cm for delta-mean scores, and 3.16 to 6.44 cm for peak and delta-peak scores. For palatability ratings the CR values varied more, ranging from 2.38 (taste) to 8.70 cm (aftertaste). Part of the difference in satiety ratings could be explained by the differences in palatability ratings. However, the low reproducibility may also be caused by a conditioned satiation or hunger due to the subjects' prior experience of the meals and therefore not just be a reflection of random noise. It is likely, however, that the variation in appetite ratings is due both to methodological day-to-day variation and to biological day-to-day variation in subjective appetite sensations. PMID- 7794871 TI - Food intake in a west African village. Estimation of food intake from a shared bowl. AB - Novel methodology is described for the estimation of food intake in the particularly difficult circumstance where groups of people eat directly from a shared bowl of cooked food. Detailed observation and measurement of meal preparation is combined with food table values for composition to calculate the nutrient content of each meal. The distribution of food between individuals is estimated by a suitable algorithm. The ability of the algorithm to identify seasonal changes in energy intakes is demonstrated by comparison of the calculated energy intakes with values for the total energy expenditure of free living adult male subjects, as measured by the stable isotope, doubly-labelled water technique. This comparison suggests that the energy intake calculated from detailed observation of two cooked meals per day is equivalent to approximately 80% of the total energy expenditure and, by inference, total dietary energy intake. The remaining energy intake may well be derived from uncooked 'snack foods', such as raw fruit and vegetables, or from cooked food obtained, by purchase or as a gift, away from the home. This is the first description of a successful method for the estimation of food intake when people eat directly from shared bowls of food. PMID- 7794870 TI - Validation of weighed records and other methods of dietary assessment using the 24 h urine nitrogen technique and other biological markers. AB - Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion:dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1.13. Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r -0.62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0.74 and 0.82, and between dietary vitamin C and beta-carotene and plasma vitamin C and beta-carotene 0.86 and 0.48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0.78-0.87). Those between N from estimated food records and urine N were r 0.60-0.70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0.01 to 0.5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy. PMID- 7794872 TI - Energy expenditure, physical activity and basal metabolic rate of elderly subjects. AB - Energy expenditure, and therefore energy requirement, generally decreases with advancing age because of a decrease in basal metabolic rate (BMR) and physical activity. The aim of the present study was to measure total energy expenditure (EE) and activity level in a group of healthy elderly (sixteen men aged 71.3 (SD 4.9) years; ten women aged 67.6 (SD 4.1) years) and young adults (nineteen men aged 30.4 (SD 5.0) years; ten women aged 27.2 (SD 3.9) years) by using the doubly labelled water method in combination with measurements of BMR. Age-related differences in body composition and their relationship to BMR and activity level were studied. EE was lower in elderly compared with young adults, partly due to a significantly lower BMR. The lower BMR was not fully explained by the lower fat free mass (FFM) in the elderly. Energy expended (MJ/d) on activity was higher for the younger subjects although there was no significant difference in the physical activity index (PAI = EE/BMR) between the two age groups. The effect of physical activity level is twofold: first it has a positive effect on the BMR, and second it has a positive effect on the FFM. Both effects involve an increase in the total EE with an increased level of physical activity. At energy balance this will lead to increased energy and nutrient intake, making especially the elderly less vulnerable to inadequate energy and nutrient intake. PMID- 7794873 TI - Characterization of an antithrombotic peptide from kappa-casein in newborn plasma after milk ingestion. AB - Bovine and human kappa-caseinoglycopeptides, two antithrombotic peptides derived from the corresponding kappa-caseins, were detected in physiologically active concentrations in the plasma of 5-d-old newborn infants after ingestion of cow's milk-based formula or human milk respectively. It is suggested that these two bioactive peptides are released from milk proteins during digestion. PMID- 7794874 TI - Feed consumption, growth and growth efficiency of rainbow trout (Oncorhynchus mykiss (Walbaum)) fed on diets containing a bacterial single-cell protein. AB - The aim of the present study was to compare the nutritive value of bacterial single-cell protein (BSCP) with that of fishmeal in rainbow trout (Oncorhynchus mykiss (Walbaum)). Four diets were formulated to contain a total of 458 g crude protein/kg of which 0% was from BSCP in diet 1 (BSCP-0), 25% in diet 2 (BSCP-25), 62.5% in diet 3 (BSCP-62.5) and 100% in diet 4 (BSCP-100); the remainder of the protein was from fishmeal. There were two studies: in study 1, duplicate groups of twenty-five fish were fed on one of the four experimental diets at the rate of 20 g/kg body weight per d for 132 d. Feed consumption rates of individual fish were measured using radiography and the overall apparent absorption efficiency for N in each group was measured over a 2-week period. In study 2, N intake, consumption, absorption and accretion were measured for each fish under controlled environmental conditions (12 h: 12 h light-dark regime; 14 degrees). Higher dietary levels of BSCP resulted in significantly higher feed consumption rates but reduced N absorption efficiency and growth rates. However, a diet containing 25% BSCP (75% fishmeal) did not significantly influence growth rates, feed consumption and absorption efficiency compared with a 100% fishmeal diet. The N growth efficiencies were highest in fish fed on the diet containing the highest level of fishmeal and significantly decreased with increasing BSCP content. Construction of N budgets demonstrated that the reduction in growth in fish eating an increasingly larger proportion of BSCP was due to a decrease in N absorption and an increase in the excretion of urea. PMID- 7794875 TI - The proportion of trans monounsaturated fatty acids in serum triacylglycerols or platelet phospholipids as an objective indicator of their short-term intake in healthy men. AB - Unfavourable effects of trans monounsaturated fatty acid (trans-C18:1) isomers on health variables have been reported. Reports on their actual intake, however, are scarce, because of the absence in many nutrient databases of values for trans C18:1, and the wide variation in the level of trans fatty acids between different brands of the same product. We therefore examined whether the intake of trans C18:1 is reflected by trans-C18:1 concentrations in serum triacylglycerols or platelet phospholipids. Thirty-eight men received two diets in random order. During the first experimental period twenty men consumed a Western-type control diet for six weeks, and eighteen men consumed a modified diet in which 70% of the fat was replaced by palm oil. After a wash-out period of 3 weeks, regimens were crossed over (second experimental period). The proportion of total fatty acids from trans-C18:1 in the diet decreased from 4.7 (SEM 0.27) during the control to 2.1 (SEM 0.16) on the modified diet (P < 0.001). Trans-C18:1 in serum triacylglycerols decreased from 3.5 (SEM 0.13) to 2.8 (SEM 0.11)% (P < 0.001), and in platelet phospholipids from 1.0 (SEM 0.06) to 0.7 (SEM 0.04)% (P < 0.001). After the first experimental period trans-C18:1 in the diet correlated with trans C18:1 in serum triacylglycerols (r 0.41; P = 0.014), and platelet phospholipids (r 0.52; P = 0.001). Also, differences in the intake between the two periods correlated with changes in the proportion of trans-C18:1 in serum triacylglycerols (r 0.56; P = 0.001) and platelet phospholipids (r 0.58; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794876 TI - The glycaemic index of foods containing sugars: comparison of foods with naturally-occurring v. added sugars. AB - The primary aim of the present study was to expand the glycaemic index (GI) database by determining the GI and insulin index values of thirty-nine foods containing sugars in healthy adults. The second aim was to examine the hypothesis that glycaemic and insulin responses to foods which contain added sugar(s) are higher than responses to foods containing naturally-occurring sugars. Eight healthy subjects drawn from a pool of eighteen consumed 50 g carbohydrate portions (except 25 g carbohydrate portions for fruits) of the test foods. The GI and insulin index were determined according to standardized methodology and expressed on a scale on which glucose = 100. The median GI and insulin index values of all foods tested were 56 (range 14 to 80) and 56 (range 24 to 124) respectively. The median GI of the foods containing added sugars was similar to that of foods containing naturally-occurring sugars (58 v. 53 respectively, P = 0.08). Likewise, the median insulin index of the foods containing added sugars was not significantly different from that of foods containing naturally-occurring sugars (61 v. 56 respectively, P = 0.16). There was no evidence of 'rebound hypoglycaemia' or excessive insulin secretion relative to the glucose response. We conclude that most foods containing sugars do not have a high GI. In addition, there is often no difference in responses between foods containing added sugars and those containing naturally-occurring sugars. PMID- 7794878 TI - Relationship between dietary Na+ intake, aldosterone and colonic amiloride sensitive Na+ transport. AB - The effect of changes in dietary Na+ intake on plasma aldosterone levels and electrogenic amiloride-sensitive Na+ transport (Iamil) was studied in the rat distal colon. Five groups of rats were fed on diets containing different amounts of Na+. Estimated Na+ intake ranged from about 400-80,000 mu equiv Na+/kg body weight (BW) per d. Both variables investigated, Iamil and plasma aldosterone, depended non-linearly on Na+ intake. Reduction of the daily Na+ intake increased plasma aldosterone levels and if these levels reached the value 200 pg/ml or more then Iamil was induced. The corresponding Na+ intake was 1300 mu equiv Na+/kg BW per d. Iamil was not observed at lower aldosterone levels and higher Na+ intakes. Aldosterone infusion for 7 d produced similar changes in Iamil compared with dietary Na(+)-depleted animals and made the estimation of maximum transport capacity of Iamil possible. We conclude that Iamil operates only if Na+ intake decreases below minimal Na+ requirement in growing rats and that the maximum transport capacity of this pathway is reached only after very severe Na+ deprivation. PMID- 7794877 TI - Relationship between smoking and antioxidant nutrient status. AB - The present study was designed to investigate the relationship between smoking and antioxidant nutrient intake and status. Smoker (n 44) and non-smoker (n 44) male students attending Dhaka University, aged between 22 and 28 years and living in a University Hall of Residence, were selected for the present study. Mean age, body weight, BMI and blood pressure were similar for both the smokers and non smokers. Mean energy, protein and fat intakes were similar for both groups. Smokers had lower intakes of dietary vitamin C, carotenes and Zn but only the difference in Zn intake was statistically significant. There was no significant difference between smokers and non-smokers for either serum vitamin A (retinol) or vitamin E (alpha-tocopherol) level. The plasma vitamin C level of smokers was significantly lower than that of non-smokers (P = 0.0004). Smokers had significantly lower serum Cu (P = 0.04) and higher serum Zn levels (P = 0.003). Further, a significant dose-response relationship between smoking and vitamin C status was observed. Linear-regression analysis showed a significantly positive correlation between dietary intake and plasma vitamin C values in non-smokers (r 0.50; P = 0.0005). On the contrary, no such association was observed in smokers. These findings suggest that smoking may cause an imbalance in antioxidant nutrient intake and status. PMID- 7794879 TI - Blood pressure changes induced by chronic insulin treatment in Wistar rats. AB - Hyperinsulinaemia may play a causal role in the development of hypertension in obese hypertensives. However, experimental evidence supporting this statement is inappropriate. The main purpose of this study was to evaluate the chronic effects of insulin administration on blood pressure, total-body glucose metabolism and urinary catecholamine excretion. After 10 weeks of insulin injection blood pressure was substantially increased in insulin-treated animals compared to those treated with saline (125 +/- 2 vs 108 +/- 2 mm Hg, p < 0.001). There were no differences in glycaemia, plasma triglyceride levels and free fatty acid levels between these two groups. Plasma level of corticosterone was increased in both insulin-treated and saline-treated rats as compared to untreated animals suggesting that the level of stress was similar in both injected groups. The urinary excretion of norepinephrine and dopamine was increased in the insulin injected group by about 120% and 310%, respectively. Our data clearly indicate that long-term insulin administration increased blood pressure but the underlying mechanisms remain to be elucidated. PMID- 7794880 TI - Amino acid transport in the small intestine. PMID- 7794881 TI - Circadian rhythm of the ventricular fibrillation threshold in female Wistar rats. AB - The circadian rhythm of ventricular fibrillation threshold (VFT) and its relation to the heart rate (HR) and the rectal temperature (RT) was studied in female Wistar rats. The animals were exposed to daily light-dark cycles of 12 h of light alternating with 12 h of darkness and were under pentobarbital anaesthesia (40 mg/kg i.p.). The experiments were performed on open chest animals and VFT was measured by direct stimulation of the myocardium. VFT in female rats showed a circadian rhythm with the acrophase -338 degrees (at 22.53 h), with the mesor 2.58 mA and the amplitude 0.33 mA. HR was not significantly changed during the experiments and no dependence was found between VFT and HR during the whole 24 hour period (r = 0.08). The acrophase of the circadian rhythm of HR (on -47 degrees, i.e. at 03.08 h) was shifted to the acrophase of VFT. The circadian rhythms of RT before the application of the anaesthetic agent and under general anaesthesia before the operative interventions had a very similar course with the nearly corresponding acrophases as the circadian rhythm of VFT. It is concluded that the electrical stability of the rat heart measured by VFT shows the significant circadian rhythm in a parallel with the circadian rhythm of RT and probably without dependence on the changes of HR. PMID- 7794882 TI - Can haloperidol disguise fever? AB - Haloperidol when applied intraperitoneally to cold-exposed febrile rabbits induces a strong hypothermic effect. This effect is due to the downward shift of the threshold central temperature for induction of cold thermogenesis and vasomotion. The shift occurs during the early phase of the fever and is less prominent during the late phase of the fever. The hypothermic effect of high doses of haloperidol can eliminate the increase of body temperature in febrile individuals. PMID- 7794883 TI - Interaction between glycine and glutamate in the development of spontaneous motility in chick embryos. AB - In this study we investigated whether also glycine fulfils the function as co activator in glutamatergic activation of NMDA receptors in the neuronal apparatus of spontaneous motility in chick embryos. The successive application of glycine (5 or 10 mg/kg egg weight (e.w.) and glutamate (15 mg/kg e.w.) in a 10 min interval significantly increased the activation of spontaneous motility of 17-day old chick embryos in comparison with the effect of glutamate alone. This effect did not depend on the order of application of the drugs. In 13-day-old embryos, glycine was ineffective in both doses. It is concluded from these results that the modulatory effect of glycine is evidently a later developmental acquisition (after day 15 of incubation) in the embryogenesis of NMDA-ergic activation of spontaneous motility in chick embryos similarly as glycinergic inhibition. PMID- 7794885 TI - Ontogenesis of melatonin receptors in anterior pituitary and pars tuberalis of golden hamsters. AB - The ontogenesis of melatonin receptors in the anterior pituitary and pars tuberalis of the Golden hamster was studied using [125I]iodomelatonin as a ligand. The affinity of the binding site to the ligand (Kd) was in the range 21 to 54 pM and it did not change significantly during development. The concentration of the [125I]iodomelatonin binding sites in the anterior pituitary was highest in one-day-old hamsters (Bmax = 14 fmol/mg protein) and thereafter gradually decreased. In adults it reached to about 6% of the neonatal values. In contrast, the concentration of the binding sites in pars tuberalis did not change significantly during ontogenesis and it was in the range of 3 to 5 fmol/mg protein. PMID- 7794884 TI - The contribution of foot deformation to the changes of muscular length and angle in the ankle joint during standing in man. AB - This study was designed to evaluate the extent of foot deformation in healthy subjects during standing on an immobile support and during slow tilts of the support platform by 1 deg. The angle in ankle joint was evaluated by two methods: as an angle of skin inclination relative to the platform and as an angle, calculated on the basis of recording of the projective length of the soleus muscle. It was shown that the real changes of the angle in ankle joint during standing on an immobile platform were up to 2 times smaller than the changes of angular position of the shin relative to vertical axis. However, considerable intersubject variability was observed in this respect. During slow tilts of the support platform a marked divergence was observed in the shape of recordings of two "ankle angles" in subjects with high foot compliance. The vertical displacements of the calcaneus recorded by means of a clamp rigidly fixed at the heel were 0.5 +/- 0.3 mm (the range 0.1-1 mm) for each degree of body deviation in the forward or backward direction. In 12 subjects, the average foot compliance was 0.04 +/- 0.03 deg/Nm (maximal value 0.1 deg/Nm). It can be assumed that the mechanical properties of the foot can appreciably influence the afferent outflow during maintenance of orthograde posture in man. PMID- 7794886 TI - Hepatocyte proliferation in silicotic rat liver after partial hepatectomy. AB - Liver silicosis was induced in rats by an intravenous injection of silica particles. The presence of silicotic granulomas in the liver lowered the initial response of hepatocytes to partial (37%) hepatectomy and slowed down the decline in the number of dividing cells 6 days after the stimulus, but did not affect significantly the total number of mitotic cells. PMID- 7794887 TI - Protective effect of carnitine on lipoperoxide formation in rat brain. AB - Carnitine administration (by intraperitoneal injection) to 21-day-old-rats prevents the increase of thiobarbituric acid-reactive substances (index of lipid peroxidation and free radical damage) induced by 30 min hypobaric hypoxia in four different parts of the brain (cerebral cortex, subcortical structures, medulla oblongata and cerebellum). PMID- 7794888 TI - Acid-base catalytic mechanism and pH dependence of fructose 2,6-bisphosphate activation of the Ascaris suum phosphofructokinase. AB - A form of phosphofructokinase (PFK) from Ascaris suum desensitized to hysteresis in the reaction time course and ATP allosteric inhibition has been used to study the activation by fructose 2,6-bisphosphate (F26P2) at varied pH in both reaction directions. In the direction of phosphorylation of F6P, V and V/KMgATP are constant over the pH range 6-9, while V/KF6P decreases at low pH, giving a pK value of 7.0, and at high pH, giving a pK of 8.9. V and V/KMgATP are insensitive to the presence of F26P2, but V/KF6P is increased by a constant amount in the presence of saturating F26P2 over the entire pH range studied. The concentration of F26P2 that gives half the change in V/KF6P, Kact, increases as the pH decreases, giving a pK of 7.4, reflecting an enzyme group that must be unprotonated for optimum binding of F26P2. In the direction of phosphorylation of MgADP, V and V/KMgADP are pH-independent, and both are insensitive to the presence of F26P2. V/KFBP decreases at high pH, giving a pK of about 7.3, and is increased by a constant amount in the presence of F26P2 over the entire pH range studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794889 TI - Biochemical characterization of a glycosylphosphatidylinositol-linked hyaluronidase on mouse sperm. AB - On the basis of DNA homology to bee venom hyaluronidase, it was recently suggested that the GPI-linked mammalian sperm antigen, PH-20, may function as a cell surface hyaluronidase [Gmachl, M., & Kreil, G. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3569-3573]. We have quantified the activity of the soluble acrosomal hyaluronidase of mouse sperm and further demonstrate the existence of a membrane bound hyaluronidase, detected on both acrosome-intact and acrosome-reacted mouse sperm, distinct from the soluble form of the enzyme. The membrane-bound hyaluronidase was specifically released by PI-PLC, indicating that it is GPI linked. Acrosome-intact and acrosome-reacted sperm released several polypeptides (68, 44, 39, 34, 17, and 15 kDa) when treated with PI-PLC. In addition, GPI linked polypeptides unique to acrosome-intact or to acrosome-reacted sperm were identified. Fractionation of the PI-PLC-released components from acrosome-reacted sperm using size exclusion chromatography revealed a single peak of hyaluronidase activity which comigrates with a 68 kDa GPI-linked protein present in these fractions. Taken together, these data demonstrate the existence of at least two isoforms of hyaluronidase: a soluble form within the acrosomal vesicle which is released during acrosomal exocytosis and a GPI-linked form which is present on the surface of both acrosome-intact and acrosome-reacted sperm. Both forms may be necessary for successful penetration of the extracellular vestments that surround the egg prior to fertilization. PMID- 7794891 TI - Multiple enzymatic activities of the human cytosolic 85-kDa phospholipase A2: hydrolytic reactions and acyl transfer to glycerol. AB - The recombinant human 85-kDa cytosolic phospholipase A2 (cPLA2), when assayed in the presence of glycerol, catalyzes the transfer of acyl chains of radiolabeled phosphatidylcholine and para-substituted phenyl esters of fatty acids to glycerol, in addition to hydrolyzing these substrates. The product of the transacylation reaction is monoacylglycerol (MAG), and the acyl chain is predominantly esterified (> or = 95%) to a primary hydroxyl group of glycerol (sn 1/3); the stereochemistry is not known. Increasing concentrations of glycerol accelerate enzyme turnover both by providing an additional mechanistic pathway for the enzyme-substrate complex to form products and by increasing the intrinsic hydrolytic and transacylation activities of the enzyme. Significant enzymatic hydrolysis of sn-1/3-arachidonylmonoacylglycerol was measured, while sn-1/3-alpha linolenoyl- and sn-2-arachidonylmonoacylglycerols were not detectably hydrolyzed. 1,3-Propanediol also serves as an acyl acceptor for the enzyme. cPLA2 hydrolyzes analog of lysophosphatidylcholine that lacks the sn-2 hydroxyl group. The enzyme will hydrolyze sn-1-acyl chains of rac-1-(arachidonyl, alpha-linolenoyl, palmitoyl)-2-O-hexadecyl-glycero-3-phosphocholine lipids and transfer the acyl chain to glycerol. Thus, cPLA2 has phospholipase A1 activity but only if an ether linkage rather than an ester linkage is present at the sn-2 position, and it is shown that the sn-1 acyl chains of both enantiomers of phosphatidylcholine are hydrolyzed. Phenyl [14C]-alpha-linolenate and five para-substituted phenyl esters of [3H]-alpha-linolenic acid with pKa values ranging from 7.2 to 10.2 for the phenol leaving groups were incorporated into 1,2-ditetradecyl-sn-glycero-3 phosphomethanol/Triton X-100 mixed micelles as substrates for the transacylation/hydrolysis reactions of the enzyme. Average product ratios, which are defined as the amount of monoacylglycerol formed to phenyl ester hydrolyzed, were 2.1 +/- 0.1 (n = 5) for the para-substituted phenyl esters and 2.0 +/- 0.3 (n = 7) for phenyl alpha-linolenate. The similarity of the ratios, despite the range of pKa values for the leaving groups, is consistent with the formation of a common enzyme intermediate that partitions to give either fatty acid or MAG. That intermediate may be a covalent acyl enzyme. Finally, the acyl chain specificity of cPLA2 was investigated to better understand the preference of the enzyme for phospholipids with sn-2-arachidonyl chains. PMID- 7794890 TI - Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure. AB - The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical properties during vesicle hydrolysis. These changes were compared to emission spectra and fluorescence polarization results occurring upon direct addition of lysolecithin and/or fatty acid to the bilayer. The excimer to monomer ratio of 1,3-bis(1-pyrene)propane was insensitive to vesicle hydrolysis, suggesting that changes in the order of the phospholipid chains were not relevant to the effect of the hydrolysis products on phospholipase activity. The fluorescence of 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) suggested that the polarity of the bilayer in the region of the phospholipid head groups increases as the hydrolysis products accumulate in the bilayer. The fluorescence of 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) confirmed that such effects were restricted to the bilayer surface. Furthermore, the lysolecithin appeared to be the product most responsible for these changes. These results suggested that lysolecithin increases the activity of phospholipase A2 during vesicle hydrolysis by disrupting the bilayer surface, making the phospholipid molecules more accessible to the enzyme active site. PMID- 7794892 TI - A nontransportable substrate for lactose permease. AB - A substrate for lactose permease of Escherichia coli was synthesized that binds to the protein with a relatively high affinity, but is not transported to any detectable extent. This substrate, 6'-[(N-phenylalanylphenylalanyl)amino]hexyl 1 thio-beta-D-galactoside, is a peptide galactoside composed of a bulky aromatic dipeptide that is linked to galactose via an aminohexyl spacer. Binding of the peptide galactoside to lactose permease in cytoplasmic membranes was determined in a competition assay yielding a dissociation constant of 150 microM. Transport was measured by a counterflow assay using lipid vesicles with reconstituted lactose permease. An upper limit for the rate constant of transport was obtained as 0.02 s-1, 3 orders of magnitude smaller than the value for lactose. PMID- 7794893 TI - FT-IR spectroscopy of the major coat protein of M13 and Pf1 in the phage and reconstituted into phospholipid systems. AB - FT-IR spectroscopy has been applied to study the secondary structure of the major coat protein of Pf1 and M13 as present in the phage and reconstituted in DOPG and mixed DOPC/DOPG (4/1) bilayers. Infrared absorbance spectra of the samples were examined in dehydrated films and in suspensions of D2O and H2O. The secondary structure of the coat protein is investigated by second-derivative analysis, Fourier self-deconvolution, and curve fitting of the infrared bands in the amide I region (1600-1700 cm-1). It is found that, in dehydrated films of Pf1 and M13 phage, the amide I region contains three bands located at about 1633, 1657, and 1683 cm-1, that are assigned to hydrogen-bonded turn, alpha-helix/random coil, and non-hydrogen-bonded turn, respectively. From a comparison of the infrared spectra in dehydrated film with those in aqueous suspension, the percentages of secondary structure were found with an accuracy of about +/- 5%. For the coat protein of Pf1 phage, the FT-IR quantification gives 69% alpha-helix conformation, 19% turn structure, and 12% random coil structure. For Pf1 coat protein in the membrane-embedded state, the amount of alpha-helix is 57%, whereas 42% is in a turn structure and 1% in a random coil structure. The same assignment strategy was used for the analysis of the data obtained for M13 coat protein reconstitution into phospholipid systems. For M13 coat protein in the phage, this gives 75% alpha-helix conformation, 21% turn structure, and 4% random coil structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794894 TI - Interactions of myogenic bHLH transcription factors with calcium-binding calmodulin and S100a (alpha alpha) proteins. AB - MyoD belongs to a family of myogenic basic helix-loop-helix (bHLH) transcription factors that activate muscle-specific genes. The basic helix I sequence of the bHLH motif contains a consensus sequence for protein kinase C (PKC) substrates. We show here that MyoD is indeed phosphorylated by PKC in vitro on Thr 115 within the basic part of the bHLH motif. By analogy with calmodulin-target peptide models, we also identified within the consensus basic helix I motif of myogenic proteins a conserved putative calmodulin/S100-binding domain. Calcium-dependent interaction between MyoD with calmodulin and the abundant muscle S100a(alpha alpha) proteins was demonstrated by affinity chromatography and cross-linking experiments. The binding of calmodulin and S100a inhibited MyoD phosphorylation by PKC as well as MyoD DNA binding activity. S100a was found to be more efficient than calmodulin in antagonizing DNA binding to MyoD. We next developed a rapid purification method for bacterial recombinant MyoD-bHLH domain by affinity chromatography using a calmodulin-Sepharose column and investigated the phosphorylation of that peptide by PKC and its interactions with calmodulin and S100a. We confirmed the phosphorylation of the threonine residue 115 in the MyoD bHLH by PKC with a Km of 0.8 microM. Calmodulin and S100a binding inhibited MyoD bHLH phosphorylation by PKC. A strict calcium-dependent interaction between calcium binding proteins and the MyoD-bHLH was identified by native gel electrophoresis and fluorescence spectroscopy with 5-(dimethylamino)naphthalene-1 sulfonylcalmodulin. The MyoD-bHLH bound to fluorescently labeled 5 (dimethylamino)naphthalene-1-sulfonylcalmodulin with a dissociation constant around 20 nM. S100a inhibited stoichiometrically the binding of the bHLH peptide for labeled calmodulin, suggesting an affinity of S100a for the bHLH peptide at least 1 order of magnitude higher than calmodulin. In favor of an in vivo interaction between S100a and MyoD, we report that S100a- and MyoD-like immunoreactivities colocalize in H9c2 cells, and that a significant amount of MyoD-like immunoreactivity is recovered in the S100a immunoprecipitate from crude H9c2 cell extract in the presence of calcium. We propose that myogenic proteins represent a new family of calmodulin/S100-binding PKC substrates and that calmodulin/S100a could participate in the regulation of the bHLH myogenic protein activities. PMID- 7794895 TI - Tyrosyl radical formation during the oxidative deposition of iron in human apoferritin. AB - The radical chemistry of ferritin is incompletely understood. The present study was undertaken to investigate the production of radicals in H-chain recombinant human ferritin (HuHF) and mixed H/L-chain horse spleen ferritin (HoSF) and the potential role of radicals in the oxidative deposition of iron in these proteins. Radical production follows distinct pathways for the two proteins; an intact H chain ferroxidase site is required for radical generation in both of them, however. With the H-chain HuHF, an EPR spectrum characteristic of a tyrosyl radical is seen following Fe2+ oxidation by O2 and, based on measurements with site-directed variants, is suggested to arise from residue Tyr-34 located in the vicinity of the ferroxidase site. The observation of this radical correlates with the observation of a 400-600 nm absorbance seen in stopped-flow kinetics studies which seems to require the presence of Tyr-34 (Bauminger et al. (1993) Biochem. J. 296, 709-714). The data are inconsistent, however, with the Tyr-34 radical being critically important in the protein-catalyzed mechanism of iron oxidation. Unlike HuHF, the radicals observed in L-chain-rich HoSF appear to arise from hydroxyl radical damage to the protein through Fenton chemistry. These latter radicals also appear to be centered on aromatic amino acids and may be derived from histidine. PMID- 7794896 TI - FT-IR and near-infrared FT-Raman study of aggregation of bacteriochlorophyll c in solutions: evidence for involvement of the ester group in the aggregation. AB - Ultraviolet-visible (UV-Vis) absorption, Fourier-transform infrared (FT-IR), and near-infrared (NIR)-excited FT-Raman spectra have been measured for bacteriochlorophyll c (BChl-c) in acetone, tetrahydrofuran (THF), pyridine-d5, carbon disulfide (CS2), and water-saturated carbon tetrachloride (CCl4) to investigate its aggregation in vitro. The UV-Vis absorption spectra can be classified into two groups. Group I (acetone, THF, and pyridine-d5 solutions) gives a spectrum with a Qy band around 665 nm while group II (CS2 and water saturated CCl4 solutions) shows a spectrum typical of BChl-c aggregates with a broader red-shifted Qy band. All the NIR-FT-Raman spectra, which are preresonant with the Qy band, are very close to those of chlorophyll a (Chl-a) measured in the corresponding solutions. Bands due to a C = O stretching mode of free and strongly hydrogen-bonded 13(1)-keto carbonyl groups appear near 1685 and 1645 cm 1, respectively. In contrast to the FT-Raman spectra, FT-IR spectra of the pyridine-d5 solution and group II are largely different from those of Chl-a in the corresponding solutions, suggesting that BChl-c forms quite different types of aggregates. It is clear from the IR spectra that the ester carbonyl group plays an important role in the aggregation for the pyridine-d5 and group II solutions. Of particular note is that bands due to C = O stretching modes of the ester group are observed at 1733, 1719, and 1705 cm-1 in the spectrum of BChl-c in water-saturated CCl4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794897 TI - Evidence for a mixed-ligand [4Fe-4S] cluster in the C14D mutant of PsaC. Altered reduction potentials and EPR spectral properties of the FA and FB clusters on rebinding to the P700-FX core. AB - PsaC-C14D (cysteine 14 replaced by aspartic acid) contains a [3Fe-4S] and a [4Fe 4S] cluster in the FB and FA sites of the free protein [Yu, L., Zhao, J., Lu, W., Bryant, D. A., & Golbeck, J. H. (1993) Biochemistry 32, 8251-8258]. When PsaC C14D is rebound to a photosystem I (PS I) core, the g-values of 2.043, 1.939, and 1.853 appear similar to FA in a wild-type PS I complex [Zhao, J. D., Li, N., Warren, P. V., Golbeck, J. H., & Bryant, D. A. (1992) Biochemistry 31, 5093 5099]. The reconstituted PsaC-C14D-PS I complex does not contain a [3Fe-4S] cluster; rather, a set of resonances with a rhombic line shape, a gav of approximately 1.97, and broad line widths indicate the presence of a mixed-ligand [4Fe-4S] cluster, termed FB', in the aspartate site. Both FA and FB' become photoreduced at 15 K, and show an interaction spectrum when reduced within the same reaction center. An electrochemical redox study shows that FA and FB' titrate with midpoint potentials near -600 mV at pH 10.0. Single-turnover flash experiments indicate that FA and FB' function as efficient electron acceptors at room temperature, and NADP+ photoreduction rates are about 70% that of a reconstituted PsaC-PS I complex. A population of S = 3/2, [4Fe-4S] clusters was tentatively identified in the free PsaC-C14D protein by characteristic EPR resonances in the g = 5.3 region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794898 TI - Long-range effects on the retinal chromophore of bacteriorhodopsin caused by surface carboxyl group modification. AB - Carboxyl groups of bacteriorhodopsin (bR) that are modified by 1-ethyl-3-[3 (trimethylamino)-propyl]carbodiimide (ETC) have been identified. Reaction of deionized purple membrane with a 400-fold molar excess of ETC or [14C]ETC for 1 h at 0 degree C incorporates about 3.5 mol of ETC/mol of bR. Proteinase K cleavage of ETC-modified bacterioopsin (bO) produced small 14C-labeled peptides. Amino acid sequence analysis showed three major ETC-modified residues: Glu 234, Asp 38, and Glu 74. Proteolysis of purple membrane with papain removes the ETC site at Glu 234. Treatment of ETC-modified, papain-cleaved purple membrane with hydroxylamine removes half of the remaining ETC label. Subsequent cleavage with chymotrypsin, followed by amino acid sequence analysis, revealed that most of the remaining label was at Glu 74. bR modified by ETC primarily at Glu 74 displays two alterations in the retinal chromophore, located in the membrane interior at a distance more than 2 nm away from the modified carboxyl group. (1) The acid induced purple-to-blue transition undergoes a shift in apparent pK from 3.2 to 2.3. (2) The second-order rate constant for chromophore regeneration from bO and retinal is diminished from 3600 to 1700 M-1 s-1 in membrane sheets. Most of the shift in the pK of the purple-to-blue transition can be explained by the quaternary ammonium ion of ETC attached to Glu 74 overlapping the postulated location of the guanidinium group of Arg 82.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794899 TI - Mechanism of CO oxidation by carbon monoxide dehydrogenase from Clostridium thermoaceticum and its inhibition by anions. AB - Carbon monoxide dehydrogenase (CODH) performs two distinct reactions at two different metal centers. The synthesis of acetyl-CoA from a methyl group, CO, and coenzyme A occurs at center A and the oxidation of CO to CO2 occurs at center C. In the work reported here, we have studied the mechanism of CO oxidation by CODH and its inhibition by thiocyanate. Our data are consistent with a ping-pong mechanism. A scheme to explain the first half-reaction was developed that includes binding of water and CO to the oxidized form of center C, deprotonation of coordinated water to yield enzyme-bound hydroxyl, nucleophilic attack on coordinated CO by OH- to form enzyme-bound carboxyl, and deprotonation and decarboxylation to form CO2 and the reduced form of center C. In the second half reaction, the reduced enzyme is reoxidized by an electron acceptor. CO oxidation was pH dependent. The pH dependence of kcat/Km for CO gave a single pKa of 7.7 and a maximum value at 55 degrees C and high pH of 9.1 x 10(6) M-1 s-1. The pH dependence of kcat followed a two-phase titration curve with pKa values of 7.1 and 9.5 and maximum value of kcat at 55 degrees C and high pH of 3250 s-1 (1310 mumol of CO oxidized min-1 mg-1). The pH dependencies of kcat/Km and kcat are interpreted to reflect the ionization of enzyme-bound water from binary and ternary complexes with center C. Reaction with thiocyanate, azide, or cyanate was found to cause a striking shift in the EPR spectrum of center C from gav = 1.82 (g = 2.01, 1.81, 1.65) to a two-component spectrum with gav = 2.15 (g = 2.34, 2.067, 2.03) and gav = 2.17 (g = 2.34, 2.115, 2.047). Thiocyanate acted as a mixed partial inhibitor with respect to CO. The inhibition constants were pH and temperature dependent. The pH dependencies of the inhibition constants gave pKa values of approximately 7.7. Binding of thiocyanate to the oxidized form of center C appears to be favored by a negative enthalpy that is offset by a decrease in entropy yielding a slightly unfavorable free energy of association. PMID- 7794900 TI - CYP4 isozyme specificity and the relationship between omega-hydroxylation and terminal desaturation of valproic acid. AB - The cytochrome P450-dependent terminal desaturation of valproic acid (VPA) is of both toxicological and mechanistic interest because the product, 4-ene-VPA, is a more potent hepatotoxin than the parent compound and its generation represents a rather novel metabolic reaction for the cytochrome P450 system. In the present study, lung microsomes from rabbits were identified as a rich source of VPA desaturase activity. Monospecific polyclonal antibodies directed against CYP4B1 (anti-4B) inhibited 82% of 4-ene-VPA formation, whereas monospecific polyclonal antibodies directed against CYP2B4 (anti-2B) inhibited only 15% of 4-ene-VPA formation. Anti-4B also inhibited 95% of the 5-hydroxy-VPA formation, but only 42% of 4-hydroxy-VPA formation. These data suggest that CYP4B1 accounts for more than 80% of the 4-ene- and 5-hydroxy-VPA metabolites generated by rabbit lung microsomes. CYP4B1 expressed in HepG2 cells metabolized VPA with a turnover number of 35 min-1 and formed the 5-hydroxy-, 4-hydroxy-, and 4-ene-VPA metabolites in a ratio of 110:2:1, respectively. In contrast, the lauric acid omega-hydroxylases, CYP4A1 and CYP4A3, did not give rise to detectable levels of any of these VPA metabolites. Therefore, these studies demonstrate a new functional role for CYP4B1 in the terminal desaturation and omega-hydroxylation of this short, branched-chain fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794901 TI - Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine. AB - Silver ions and silver-containing compounds have been used as topical antimicrobial agents in a variety of clinical situations. We have previously shown that the enzyme phosphomannose isomerase (PMI) is essential for the biosynthesis of Candida albicans cell walls. In this study, we find that PMI can be inhibited by silver ions. This process is shown to be irreversible, and is a two-step process, involving an intermediate complex with a dissociation constant, Ki, of 59 +/- 8 microM, and a maximum rate of inactivation of 0.25 +/- 0.04 min-1 in 50 mM Hepes buffer, pH 8.0 at 37 degrees C. The enzyme can be protected against this inactivation by the substrate mannose 6-phosphate, with a dissociation constant of 0.31 +/- 0.04 mM, close to its Km value. Flamazine (silver sulfadiazine) is a silver-containing antibiotic which is used clinically as a topical antimicrobial and antifungal agent. We compared the ability of silver sulfadiazine and two other silver-containing compounds to irreversibly inactivate C. albicans PMI. The addition of the organic moiety increased the affinity of the compounds, with silver sulfadiazine showing a Ki of 190 +/- 30 nM. In all cases, the maximum inhibition rate was similar, implying a similar rate-determining step. Silver sulfadiazine does not inhibit Escherichia coli PMI, and this suggests a role of the only free cysteine, Cys-150, in the inactivation process. To confirm this, we mutated this residue to alanine in C. albicans PMI. The resultant Cys150 --> Ala mutant protein showed similar Vm and Km values to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794902 TI - Macromolecular arrangement in the aminoacyl-tRNA.elongation factor Tu.GTP ternary complex. A fluorescence energy transfer study. AB - The distance between the corner of the L-shaped transfer RNA and the GTP bound to elongation factor Tu (EF-Tu) in the aminoacyl-tRNA.EF-Tu.GTP ternary complex was measured using fluorescence energy transfer. The donor dye, fluorescein (Fl), was attached covalently to the 4-thiouridine base at position 8 of tRNAPhe, and aminoacylation yielded Phe-tRNAPhe-Fl8. The ribose of GTP was covalently modified at the 2'(3') position with the acceptor dye rhodamine (Rh) to form GTP-Rh. Formation of the Phe-tRNAPhe-Fl8.EF-Tu.GTP-Rh ternary complex was verified both by EF-Tu protection of the aminoacyl bond from chemical hydrolysis and by an EF Tu.GTP-dependent increase in fluorescein intensity. Spectral analyses revealed that both the emission intensity and lifetime of fluorescein were greater in the Phe-tRNAPhe-Fl8.EF-Tu.GTP ternary complex than in the Phe-tRNAPhe-Fl8.EF-Tu.GTP Rh ternary complex. These spectral differences disappeared when excess GTP was added to replace GTP-Rh in the latter ternary complex, thereby showing that excited-state energy was transferred from fluorescein to rhodamine in the ternary complex. The efficiency of singlet-singlet energy transfer was low (10-12%), corresponding to a distance between the donor and acceptor dyes in the ternary complex of 70 +/- 7 A, where the indicated uncertainty reflects the uncertainty in dye orientation. After correction for the lengths of the probe attachment tethers, the 2'(3')-oxygen of the GTP ribose and the sulfur in the s4U are separated by a minimum of 49 A. This large distance limits the possible arrangements of the EF-Tu and the tRNA in the ternary complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794903 TI - Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins. AB - A number of DNA helicases have been isolated from mammalian cells, but their abilities to stimulate DNA replication accompanied with DNA unwinding have not been addressed so far. We constructed a model DNA replication system using the yeast autonomously replicating sequence (ARS) as the replication origin. In this system, SV40 T antigen as a DNA helicase assembles to the replication origin where the DNA duplex is unwound by torsional stress due to the negative supercoiling of template DNA, which leads to bidirectional DNA replication from the origin. We report here that DNA helicase B isolated from mouse FM3A cells can greatly stimulate DNA synthesis in this replication system in place of SV40 T antigen. DNA synthesis was dependent on the presence of single-stranded DNA binding protein (RP-A), DNA polymerase alpha/primase from mouse cells, and Escherichia coli DNA gyrase. DNA gyrase was required not only at elongation as a DNA swivelase but also at initiation to increase negative superhelical density of template DNA with the assistance of RP-A. A mammalian DNA fragment containing a replication initiation zone upstream of the c-myc gene as well as the yeast ARS fragment acted as a cis-element in this system using DNA helicase B. Both DNA helicase B and SV40 T antigen have the ability to extensively unwind the template DNA in the presence of RP-A and DNA gyrase, which may be crucial for stimulation of DNA synthesis in this system. PMID- 7794904 TI - Continuous fluorescence assay of phytochrome assembly in vitro. AB - Incubation of recombinant apophytochrome with the phycobiliprotein chromophore precursor phycoerythrobilin produces a covalent adduct that exhibits a fluorescence excitation maximum at 576 nm and an emission maximum at 586 nm. Using these fluorescence parameters, we have developed a kinetic assay for quantitative analysis of the assembly of the plant photoreceptor phytochrome in real time. Kinetic measurements performed with different phycoerythrobilin concentrations confirm that bilin attachment to apophytochrome involves two steps, an initial formation of a reversible non-covalent complex followed by thioether bond formation. The kinetic constants for both steps of phycoerythrobilin attachment to apophytochrome were estimated with this assay. Methodology for determining the kinetic constants for the assembly of both the natural phytochrome chromophore precursor, phytochromobilin, and the analog phycocyanobilin is also described. Since the latter two bilins yield covalent, nonfluorescent adducts with apophytochrome, their co-incubation with phycoerythrobilin reduces the rate of formation of the fluorescent phycoerythrobilin adduct in an irreversible, competitive manner. Competition experiments were also performed with biliverdin, a structurally related bilin which does not form a covalent adduct with apophytochrome. Such measurements show that biliverdin reversibly binds to apophytochrome with a submicromolar binding constant, an affinity which is very similar to that of phytochromobilin. The utility of this fluorescence assay for identification of novel inhibitors of phytochrome assembly and for characterization of the structural features of both bilin and apophytochrome necessary for photoreceptor assembly is discussed. PMID- 7794906 TI - Eukaryotic acidic phosphoproteins interact with the ribosome through their amino terminal domain. AB - Variable-size fragments of the four yeast acidic ribosomal protein genes rpYP1 alpha, rpYP1 beta, rpYP2 alpha and rpYP2 beta were fused to the LacZ gene in the vector series YEp356-358. The constructs were used to transform wild-type Saccharomyces cerevisiae and several gene-disrupted strains lacking different acidic ribosomal protein genes. The distribution of the chimeric proteins between the cytoplasm and the ribosomes, tested as beta-galactosidase activity, was estimated. Hybrid proteins containing around a minimum of 65-75 amino acids from their amino-terminal domain are able to bind to the ribosomes in the presence of the complete native proteins. Hybrid proteins containing no more than 36 amino terminal amino acids bind to the ribosomes in the absence of a competing native protein. The fused YP1-beta-galactosidase proteins are also able to form a complex with the native YP2 type proteins, promoting their binding to the ribosome. The stability of the hybrid polypeptides seems to be inversely proportional to the size of their P protein fragment. These results indicate that only the amino-terminal domain of the eukaryotic P proteins is needed for the P1 P2 complex formation required for interaction with the ribosome. The highly conserved P protein carboxyl end is not implicated in the binding to the particles and is exposed to the medium. PMID- 7794905 TI - Effects of C-terminal deletions on the conformational state and denaturation of phosphoglycerate kinase. AB - Phosphoglycerate kinase (PGK) contains two domains of approximately equal size, both of the alpha/beta type. An alpha-helix consisting of the middle section of the 415-amino acid polypeptide chain, and the N- and C-termini reside in the interdomain hinge region [Watson, H. C., et al. (1982) EMBO J. 1, 1635-1640]. The C-terminal end is an integral part of the N-terminal domain. The consequences of the deletion of fifteen and three C-terminal amino acids on the conformational state and on the guanidine hydrochloride-induced and thermal unfolding of PGK were investigated by using near- and far-UV CD, tryptophan fluorescence, 1 anilinonaphthalene-8-sulfonic acid binding, accessibility to chemical modification, and differential scanning calorimetry. The results of these studies indicate that the conformations of both domains and of the interdomain region were altered by these deletions. In the absence of the 15-amino acid C-terminal peptide [delta(401-415)], the N-terminal domain exhibits several characteristics of a molten globule state, whereas the C-terminal domain retains native-like, although distinctly different, tertiary structure. Deletion of three C-terminal amino acids [delta(413-415)] also globally affects PGK conformation, although to a much lesser extent. Both C-terminal deletions resulted in a significant decrease in protein stability, as demonstrated by their increased susceptibility to guanidine-induced and thermal denaturation. These results suggest that the formation of a native tertiary fold of PGK requires the presence of a complete polypeptide chain. PMID- 7794907 TI - Identification of Asp258 as the metal coordinate of pigeon liver malic enzyme by site-specific mutagenesis. AB - Pigeon liver malic enzyme was inactivated by ferrous sulfate in the presence of ascorbate. Manganese and some other divalent metal ions provided complete protection of the enzyme against the Fe(2+)-induced inactivation. The inactivated enzyme was subsequently cleaved by the Fe(2+)-ascorbate system at Asp258-Ile259, which was presumably the Mn(2+)-binding site of the enzyme [Wei, C. H., Chou, W. Y., Huang, S. M., Lin, C. C., & Chang, G. G. (1994) Biochemistry 33, 7793-7936]. For identification of Asp258 as the putative metal-binding site of the enzyme, we prepared four mutant enzymes substituted at Asp258 with glutamate (D258E), asparagine (D258N), lysine (D258K), or alanine (D258A), respectively. These mutant proteins were recombinantly expressed in a bacterial expression system (pET-15b) with a stretch of histidine residues attached at the N-terminus and were successfully purified to apparent homogeneity by a single Ni-chelated affinity column. Among the four mutants, only D258E possessed 0.8% residual activity after purification; all other purified mutants had < 0.0001% residual activity in catalyzing the oxidative decarboxylation of L-malate. The D258E mutant was susceptible to inactivation by the Fe(2+)-ascorbate system, albeit with much slower inactivation rate, and was protected by the Mn2+ to a lesser extent as compared to the wild-type enzyme. None of the mutants were cleaved by the Fe(2+)-ascorbate system under conditions that cleaved the natural or wild type enzyme at Asp258.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794909 TI - Interruption of the water chain in the reaction center from Rhodobacter sphaeroides reduces the rates of the proton uptake and of the second electron transfer to QB. AB - A chain of bound water molecules was recently identified in the photosynthetic reaction center (RC) from Rhodobacter sphaeroides by X-ray crystallography [Ermler et al. (1994) Structure 2, 925-936]. The possible role of the chain in proton transfer from the solution to the secondary quinone (QB) was investigated by site-directed mutagenesis and flash-induced absorbance spectroscopy. Pro L209, situated along the water chain about 9 A from QB, was changed into the aromatic residues Phe and Tyr in order to interrupt the chain. In the PL209Y (Pro L209- >Tyr) mutant, the very small changes in the QA-QB<==>QAQB- equilibrium constant (K2) and the first electron-transfer rates (kAB(1)) indicate that the mutation does not lead to large structural changes. In the PL209F (Pro L209-->Phe) mutant, a 7-fold decrease of kAB(1) is observed. It follows a pH dependence parallel to that of the wild type. It is consistent with no modification of the pK of the Glu L212 determined from the pH dependence of K2. The decreased kAB(1) may reflect some slight structural modification in this mutant and/or rearrangement of the cluster of charged residues close to the L209 position. The major effect of the mutations observed is a concomitant decrease of the rates of the second electron transfer, kAB(2), and of the proton uptake upon the second flash. The relative decrease of the kAB(2) rate values in the mutants is more pronounced above pH 8. Our results indicate that the mutations have specifically altered the pathway of proton transfer to QB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794908 TI - Efflux of cellular cholesterol and phospholipid to lipid-free apolipoproteins and class A amphipathic peptides. AB - The mechanism(s) by which lipid-free apolipoprotein (apo) AI is able to stimulate efflux of cholesterol and phospholipid from cells in cultures has (have) been examined. This process was found to be enhanced when macrophages were enriched with cholesterol. There were 12- and 4-fold increases in cholesterol and phospholipid efflux, respectively, from cholesterol-enriched mouse macrophages when compared to cells not loaded with cholesterol. This enhancement in cholesterol efflux to lipid-free apo AI from macrophages enriched with cholesterol was found to be controlled by the level of free cholesterol in the cells. When cholesterol-enriched mouse macrophages were exposed to lipid-free apo AI at 20 micrograms/mL (706 nM), there was significant efflux of [14C]cholesterol and [3H]phospholipid (20% +/- 0.5%/24 h and 6% +/- 0.3%/24 h, respectively). In comparison, HDL at equivalent protein concentrations only stimulated 11% and 4% efflux of cholesterol and phospholipid, respectively. Synthetic peptides containing amphipathic helical segments that mimic those present in apo AI were used to examine the structural features of the apoprotein which stimulate lipid efflux. Peptides containing only one (18A) or two (37pA) amphipathic helical segments stimulated as much cholesterol efflux from both mouse macrophages and L cells as apo AI. The order of efficiency, as assessed by the mass concentration at which half-maximal efflux was reached (EC50), was apo AI > 37pA > 18A, indicating that acceptor efficiency was dependent on the number of amphipathic helical segments per molecule. When the helical content of 18A was increased by neutralizing the charges at the ends of the peptide (Ac-18A-NH2), there was a substantial increase in the efficiency for cholesterol efflux (EC50 18A = 17 micrograms/mL vs Ac-18A-NH2 = 6 micrograms/mL). In contrast, when the amphipathicity of the helix in 18A was decreased by scrambling the amino acid sequence, thereby reducing its lipid affinity, cholesterol and phospholipid efflux were not stimulated. The efficiency with which the peptides stimulated cholesterol efflux was in order of their lipid affinity (37pA > Ac-18A-NH2 > 18A), and this order was similar for phospholipid efflux. The time course of lipid release from mouse macrophages and L-cells indicated that phospholipid appeared in the extracellular medium before cholesterol. These results suggest that the apo AI or peptides first interacted with the cell to form protein/phospholipid complexes, that could then accept cholesterol. PMID- 7794910 TI - Three-dimensional structure of the binuclear metal center of phosphotriesterase. AB - Phosphotriesterase, as isolated from Pseudomonas diminuta, is capable of detoxifying widely used pesticides such as paraoxon and parathion and various mammalian acetylcholinesterase inhibitors. The enzyme requires a binuclear metal center for activity. Recently, the three-dimensional structure of the apoenzyme was solved (Benning et al., 1994) and shown to consist of an alpha/beta-barrel. Here we describe the three-dimensional structure of the holoenzyme, reconstituted with cadmium, as determined by X-ray crystallographic analysis to 2.0-A resolution. Crystals employed in the investigation belonged to the space group C2 with unit cell dimensions of a = 129.5 A, b = 91.4 A, c = 69.4 A, beta = 91.9 degrees, and two subunits in the asymmetric unit. There are significant differences in the three-dimensional architecture of the apo and holo forms of the enzyme such that their alpha-carbon positions superimpose with a root-mean square deviation of 3.4 A. The binuclear metal center is located at the C terminus of the beta-barrel with the cadmiums separated by 3.8 A. There are two bridging ligands to the metals: a water molecule (or possibly a hydroxide ion) and a carbamylated lysine residue (Lys 169). The more buried cadmium is surrounded by His 55, His 57, Lys 169, Asp 301, and the bridging water in a trigonal bipyramidal arrangement. The second metal is coordinated in a distorted octahedral geometry by His 201, His 230, Lys 169, the bridging water molecule, and two additional solvents. PMID- 7794911 TI - Characterization of a hormone-inducible, high affinity adenosine 3'-5'-cyclic monophosphate phosphodiesterase from the rat Sertoli cell. AB - In previous reports we have shown that FSH and beta-adrenergic agonists regulate the levels of mRNA and increase the activity of a high affinity cAMP phosphodiesterase (cAMP-PDE) in the immature rat Sertoli cell in culture. To identify and characterize the hormone-inducible form(s), the cAMP-PDE activity of the Sertoli cell was partially purified and its properties were determined using biochemical and immunological tools. The cAMP-PDE activity present in the 100,000g supernatant of Sertoli cell extracts was purified more than 2000-fold by four HPLC chromatographic steps. The major purified form of cAMP-PDE had a specific activity of 1-2 mumol/(min.mg of protein). Polyacrylamide gel electrophoresis and silver staining analysis showed that a 67-68 kDa polypeptide comigrated with the major peak of cAMP hydrolytic activity. The molecular weight of the crude or purified enzyme determined by gel filtration and sucrose density gradients was 150,000, suggesting that the native enzyme is an oligomeric structure. This PDE hydrolyzed cAMP with a Km of 1.97 +/- 0.26 microM. The hydrolysis of cAMP was neither inhibited nor stimulated by cGMP concentrations lower than 50 microM. Cyclic nucleotide catalysis required Mg2+, but was insensitive to Ca2+. The activity of this form was competitively inhibited by several inhibitors with the following potency: rolipram > RO 20-1724 > methylisobutylxanthine > cilostamide = milrinone. Because mRNAs derived from two distinct PDE4B and PDE4D genes are present in the Sertoli cell, selective and nonselective PDE antibodies were used to determine the origin of the inducible PDE protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794912 TI - "Prohormone thiol protease" (PTP) processing of recombinant proenkephalin. AB - The "prohormone thiol protease" (PTP) from adrenal medullary chromaffin granules has been demonstrated as a novel cysteine protease that converts the model enkephalin precursor, ([35S]Met)-preproenkephalin, to appropriate enkephalin related peptide products [Krieger, T. J., & Hook, V. Y. H. (1991) J. Biol. Chem. 266, 8376-8383; Kreiger, T. J., Mende-Mueller, L., & Hook, V. Y. H. (1992) J. Neurochem. 59, 26-31; Azaryan, A. V., & Hook, V. Y. H. (1994) FEBS Lett. 341, 197 202]. In this report, PTP processing of authentic proenkephalin (PE) was examined with respect to production of appropriate intermediate products, and kinetics of PE processing were assessed. Recombinant PE was obtained by high level expression in Escherichia coli, with the pET3c expression vector; PE was then purified from E. coli by DEAE-Sepharose chromatography, preparative gel electrophoresis, and reverse-phase HPLC. Authentic purified PE was confirmed by amino acid composition analyses and peptide microsequencing. In time course studies, PTP converted PE (12 microM) to intermediates of 22.5, 21.7, 12.5, and 11.0 kDa that represented NH2-terminal fragments of PE, as assessed by peptide microsequencing. Differences in molecular masses of the 22.5, 21.7, 12.5, and 11.0 kDa products reflect PTP processing of PE within the COOH-terminal region of PE, which resembles PE processing in vivo [Liston, D. L., Patey, G., Rossier, J., Verbanck, P., & Vanderhaeghen, J. (1983) Science 225, 734-737; Udenfriend, S., & Kilpatrick, D. L. (1983) Arch. Biochem. Biophys. 221, 309-314]. Products of 12.5, 11.0, and 8.5 kDa were generated by PTP cleavage between Lys-Arg at the COOH-terminus of (Met)enkephalin-Arg6-Gly7-Leu8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794914 TI - Evidence for ternary complex formation by histone H1, DNA, and liposomes. AB - Using three different donor-acceptor pairs for resonance energy transfer, interactions in systems composed of histone H1, liposomes, and DNA were investigated. While weak attachment of H1 to phosphatidylcholine (PC) liposomes was observed, the inclusion of phosphatidylserine (PS), phosphatidylglycerol (PG), or phosphatidic acid (PA) strongly enhanced the membrane association of H1, the extent of binding increasing with the content of the acidic lipid. Increasing the content of the negatively charged lipid also made the membrane attachment of H1 less susceptible to dissociation by NaCl, thus indicating, in keeping with our previous studies, that protonation of the acidic lipid is an important factor. Whereas DNA binds to sphingosine-containing cationic liposomes, these vesicles did not bind H1. Instead, H1 effectively competed with sphingosine for binding with DNA. In systems comprising DNA, liposomes, and H1, the interactions were clearly dependent on the liposome composition. While moderately acidic liposomes (PS content < 30 mol%) seemed to form ternary complexes with DNA and H1, strongly acidic liposomes (PS content > 30 mol %) competed with DNA for binding H1, partly removing the histone from the nucleic acid. The tendency to form ternary complexes also seemed to depend on the type of the acidic lipid. Possible physiological consequences of the interactions detected in these simple model systems are discussed. PMID- 7794913 TI - Yeast TATA binding protein interaction with DNA: fluorescence determination of oligomeric state, equilibrium binding, on-rate, and dissociation kinetics. AB - A combination of steady-state, stopped-flow, and time-resolved fluorescence of intrinsic tryptophan and extrinsically labeled fluorescent DNA is utilized to examine the interaction of yeast TATA binding protein (TBP) with DNA. TBP is composed of two structural domains, the carboxy domain (residues 61-240), which is responsible for DNA binding and initiation of basal level transcription, and an amino terminal domain (residues 1-60), whose function is currently unknown. The steady-state fluorescence emission spectrum of the single tryptophan in the amino terminal domain of TBP undergoes a huge (30-40 nm) red-shift upon interaction with stoichiometric amounts of TATA box containing DNA. From time resolved tryptophan fluorescence anisotropy studies, we demonstrate that, in the absence of DNA, the protein exists as a multimer in solution and it contains (at least) two primary conformations, one with the amino terminus associated tightly with the protein(s) in a hydrophobic environment and one with the amino terminus decoupled away from the rest of the protein and solvent-exposed. Upon binding DNA, the protein dissociates into a monomeric complex, upon which only the solvent-exposed amino terminus conformation remains. Kinetic and equilibrium binding studies were performed on TATA box containing DNA which was extrinsically labeled with a fluorescent probe Rhodamine-X at the 5'-end. This "fluorescent" DNA allowed for the collection of quantitative spectroscopic binding, kinetic on rate, and kinetic off-rate data at physiological concentrations. Global analysis of equilibrium binding studies performed from 500 pM to 50 nM DNA reveals a single dissociation constant (Kd) of approximately 5 nM. Global analysis of stopped-flow anisotropy on-rate experiments, with millisecond timing resolution and TBP concentrations ranging from 20 to 600 nM (20 nM DNA), can be perfectly described by a single second-order rate constant of 1.66 x 10(5) M(-1) s(-1). These measurements represent the very first stopped-flow anisotropy study of a protein/DNA interaction. Stopped-flow anisotropy off-rate experiments reveal a single exponential k(off) of 4.3 x 10(-2) min-1 (1/k(off) = 23 min) From the ratio of on-rate to off-rate, a predicted Kd of 4.3 nM is obtained, revealing that the kinetic and equilibrium studies are internally consistent. Deletion of the amino terminal domain of TBP decreases the k(on) of TBP approximately 45-fold and eliminates classic second-order behavior. PMID- 7794915 TI - Transcriptional regulation of human CYP2C genes: functional comparison of CYP2C9 and CYP2C18 promoter regions. AB - The cytochrome P4502C subfamily comprises a group of constitutive microsomal hemoproteins which are expressed primarily in liver. In humans, this subfamily is responsible for metabolism of a variety of therapeutic drugs such as warfarin, mephenytoin, omeprazole, and antiinflammatory drugs. In the present study, we analyzed the promoter activity of the 5'-flanking region of two human CYP2C genes, CYP2C9 and CYP2C18. The ability of the 2.2-kb 5'-flanking region of the CYP2C9 gene to direct expression of a luciferase reporter gene in HepG2 cells was 25 times greater than that of the 1.3-kb 5'-flanking region of CYP2C18. Deletional analysis of CYP2C9 indicated that the minimal promoter was located between the translation start site and nucleotide -155, and an HPF-1 domain consensus sequence was identified in this region. Gel shift analysis demonstrated that nuclear proteins from HepG2 cells had a high binding affinity for a 20-bp oligonucleotide containing the HPF-1 site of CYP2C9. Antiserum to rat HNF-4 supershifted this DNA--protein complex, and an oligonucleotide derived from an HNF-4 motif present in the human apolipoprotein CIII promoter competed for the supershifted complex. Cotransfection with an HNF-4 expression plasmid increased transcriptional activity of the CYP2C9 minimal promoter (approximately 2-fold) in HepG2 cells and elevated activity more substantially in nonhepatic NIH3T3 cells (26-fold) and Cos 1 cells (9-fold).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794916 TI - Interaction of nucleolar protein B23 with peptides related to nuclear localization signals. AB - Nucleolar protein B23 is a putative ribosome assembly factor with a high affinity for peptides containing nuclear localization signals (NLSs). The interactions of various NLS-containing peptides with two B23 isoforms (B23.1 and B23.2) were examined using equilibrium dialysis and Scatchard analyses. The KD for protein B23 binding to a peptide containing the SV40 T-antigen NLS sequence was approximately 1 microM with a stoichiometry of 1:1 (peptide:protein). No significant differences were seen between the two B23 isoforms in their affinities for any of the peptides tested. Binding by a reverse sequence SV40 T NLS peptide showed a nonlinear Scatchard plot: this peptide was unable displace the correct sequence peptide, suggesting that the reverse sequence peptide binds to a different site on the protein. A peptide containing the sequence required for nucleolar localization of the HIV-1 Rev protein had an affinity for B23 approximately 10-fold greater than that of the SV40 T-NLS. However, with a sequence sufficient only for Rev location in the nucleoplasm, the affinity for B23 was diminished to a level between that of the longer Rev sequence and the SV40 T-NLS. In competition binding assays, the Rev NLS peptide was able to displace the SV40 T NLS, indicating that both peptides bind to the same site on protein B23. There was no detectable binding to protein B23 by a peptide containing the bipartite NLS of nucleoplasmin. Phosphorylation of protein B23 by casein kinase II enhanced its affinity for the SV40 T- and Rev-derived peptides approximately 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794917 TI - Identification and quantitation of dibenzo[a,l]pyrene--DNA adducts formed by rat liver microsomes in vitro: preponderance of depurinating adducts. AB - Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen known among aromatic hydrocarbons. DB[a,l]P-11,12-dihydrodiol, precursor to the bay-region diol epoxide, is slightly less carcinogenic than the parent compound. DB[a,l]P and its 11,12-dihydrodiol were covalently bound to DNA by cytochrome P-450 in 3 methylcholanthrene-induced rat liver microsomes, and DB[a,l]P was also bound to DNA by horseradish peroxidase. The "stable" (remaining intact in DNA under normal conditions of purification) and "depurinating" (released from DNA by cleavage of the glycosidic link between the purine base and deoxyribose) adducts were identified and quantified. Stable adducts were analyzed by the 32P-postlabeling technique. Depurinating adducts were identified by comparison of their retention times with those of standard adducts on HPLC in two solvent systems. Confirmation of their identity was obtained by means of fluorescence line-narrowing spectroscopy. When DB[a,l]P was activated by horseradish peroxidase, the depurinating adducts 3-(DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N3Ade, 33%), 7 (DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N7Ade, 27%), and 7-DB[a,l]P-10-yl)guanine (DB[a,l]P-10-N7Gua, 5%) were formed. Unidentified stable adducts comprised the remaining 35% of the detected adducts. When DB[a,l]P was activated by microsomes, the one-electron oxidation depurinating adducts DB[a,l]P-10-N3Ade (28%), DB[a,l]P 10-N7Ade (14%), DB[a,l]P-10-N7Gua (2%), and DB[a,l]P-10-C8Gua (6%), as well as the diol epoxide depurinating adducts (+/-)-syn-DB[a,l]P-diol epoxide (DE)-14 N7Ade (31%) and (+/-)-anti-DB[a,l]PDE-14-N7Gua (3%), were formed. Stable adducts predominantly formed via the DB[a,l]PDE pathway represented 16% of the adducts detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794919 TI - Characterization of gastrin-releasing peptide receptor expressed in Sf9 insect cells by baculovirus. AB - Whereas baculovirus expression systems have been extensively used for high-level expression of steroid receptors and receptors coupled to adenylate cyclase, there are few studies on peptide receptors coupled to phospholipase C (PLC). In the present study we have expressed the murine gastrin-releasing peptide receptor (mGRP-R) in Sf9 cells using a recombinant baculovirus and characterized it structurally and functionally. mGRP-R was detectible 12 h post infection with recombinant baculovirus carrying mGRP-R cDNA and became maximal at 60 h post infection (Bmax = 6 pmol/mg protein), which is a 4-60-fold greater density than is found in native tissues. The mGRP-R in Sf9 cells assessed by affinity labeling or immunoblotting was smaller than that in native tissues (M(r) = 51 kD vs 82 kD), and the difference was due to the extent of glycosylation. In Sf9 cells the mGRP-R had at least two of the four potential extracellular glycosylation sites glycosylated, whereas in the native receptor all four were approximately equally glycosylated. In Sf9 cells the glycosylation was entirely biantennary complex, in contrast to the native mGRP-R, where it was entirely tri- and tetraantennary complex N-linked oligosaccharides. Affinity labeling studies revealed a band with an apparent molecular mass about 40 kDa higher than the 51-kDa mGRP-R band. The intensity of this band correlated with the extent of functional G protein coupling, suggesting that it may represent an mGRP-R-G protein complex. In binding studies the affinity of the mGRP-r in Sf9 cells for the agonists bombesin (Bn), GRP, and neuromedin B (NMB) varied differently with infection time: with Bn the affinity decreased 3-fold with longer infection times, with GRP it remained unchanged, and with NMB it decreased 10-fold. GPP(NH)p inhibited binding of either [125I]Tyr4Bn or [125I]GRP at 24 h post infection, but not at 96 h post infection. Agonists activated PLC, increasing both [3H]IP and [Ca2+]i; however, the efficacy of each agonist decreased with infection time. These results demonstrate that by the use of recombinant baculovirus infected Sf9 cells the PLC linked receptor mGRP-R can be expressed in amounts significantly greater than those in native tissues. The mGRP-R expressed in these Sf9 cells is incompletely glycosylated and has less complex N-linked oligosaccharide chains, yet it is fully coupled to G proteins and activates phospholipase C, similar to the native receptor, if short infection times are used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7794918 TI - Binding of vinblastine to phosphocellulose-purified and alpha beta-class III tubulin: the role of nucleotides and beta-tubulin isotypes. AB - Vinblastine is an antimitotic drug that inhibits microtubule assembly and induces the self-association of tubulin into coiled spiral aggregates. Previous quantitative binding and sedimentation velocity results have been interpreted by a mechanism involving isodesmic ligand-mediated plus ligand-facilitated self association [Na, G., & Timasheff, S. N. (1986) Biochemistry 25, 6214-6222, 6222 6228]. In this study, the vinblastine-induced self-association of porcine brain tubulin has been compared in the presence of 50 microM GDP or 50 microM GTP to investigate the role of nucleotides. Experiments at 1-4 microM tubulin in 10 mM Pipes, 1 mM MgSO4, 2 mM EGTA (pH 6.9), and varying concentrations of vinblastine (0.05-70 microM) demonstrate that GDP enhances self-association by 2-4-fold over GTP. In the presence of GDP or GTP, sedimentation velocity data can be best fit by either an indefinite ligand-mediated model or an indefinite ligand-mediated plus ligand-facilitated model. The association constant, K2, for the vinblastine tubulin complex binding to a polymer is larger when GDP is present, while the association constant, K1, for the binding of vinblastine to tubulin heterodimers is identical in the presence of either nucleotide. The enhancement of K2 by GDP is confirmed by micropartition binding experiments with [3H]vinblastine. The fitting of sedimentation velocity and binding studies gives parameters for the interaction of vinblastine with GTP-tubulin that are identical, within error, to the previous results of Na and Timasheff. van't Hoff analysis of multiple temperature data reveals that this enhancement in the presence of GDP is due to a change in the enthalpy of self-association. Additional results suggest that the interaction of vinblastine with tubulin is identical for all beta-isotypes. Sedimentation velocity experiments in the presence of GDP or GTP show that the vinblastine-induced association of affinity-purified alpha,beta-class III tubulin is identical to that of unfractionated tubulin, although there is a difference in the abilities of unfractionated tubulin and alpha,beta III-tubulin to associate into taxol-stabilized microtubules. PMID- 7794920 TI - Structure-activity analysis of a Conus peptide blocker of N-type neuronal calcium channels. AB - The synthetic peptide SNX-111 corresponding to the sequence of the omega conopeptide MVIIA from the venom of the marine snail Conus magus is a highly potent and selective antagonist of N-type calcium channels. We have synthesized and characterized a large number of analogs of SNX-111 in order to elucidate the structural features of the peptide involved in blocking N-type calcium channels. Comparison of the binding of SNX-111 and its analogs to rat brain synaptosomal membranes rich in N-type channels revealed that, among the four lysines and two arginines in the molecule, lysine in position 2 and arginines at position 10 and 21 are important for the interaction of SNX-111 with N-type channels. The importance of the middle segment from residues 9 through 14 for this binding interaction was revealed by substitution of the individual residues as well as by the construction of hybrid peptides in which the residues 9-12 in SNX-111 and another conopeptide, SNX-183, corresponding to a peptide SVIB from Conus striatus, were interchanged. Introduction of the sequence SRLM from SNX-111 in place of RKTS in position 9-12 in SNX-183 resulted in a 38-fold increase in affinity. PMID- 7794921 TI - Structure-function assessment of the role of the helical stack domain in the properties of human recombinant protein C and activated protein C. AB - The role of the helical stack (HS) in defining the properties of human recombinant (r) protein C (PC) and activated protein C (APC) was assessed. To do so, several mutations were made in this region of the molecule and their effects on the proteins examined. Substitution of the entire HS of PC (residues 38-46) by that of human coagulation factor (f) IX (residues 39-47), yielding r-[HSIX]PC, did not result in any substantial changes in the gamma-carboxyglutamic acid domain (GD)-related Ca(2+)-dependent properties of PC or APC, suggesting that the conformation of the HS may play a more dominant role in these Ca(2+)-dependent properties than do the specific amino acids that differ between these two HS regions. On the other hand, the catalytic efficiency of activation of r-[HSIX]PC by the thrombin/thrombomodulin complex was reduced to approximately one-third of that of wtr-PC, a result that demonstrates a specific role for the HS of PC in this activation process. Another mutation, [Ser42-->Pro], was generated in the HS region of r-PC, providing r-[S42P]PC, a change that according to the empirical algorithm based on the Chou-Fasman secondary structure rules, would disrupt the alpha-helical conformation of the HS. The anticoagulant activity of the corresponding r-[S42P]APC was found to be approximately 35% of that of wtr-APC. Because of the lack of any notable effects of this mutation on other GD-related Ca(2+)-dependent properties of r-PC and r-APC, the basis of this anticoagulant activity loss may be due to its nonmaximal alignment with substrate on the PL surface. The results of this study indicate that the role of the HS of r-PC and r APC is to provide a region of the protein that is needed to assure optimal alignment on the PL or cell surface of the active site of the enzyme with that of the cleavage sites of the substrates, perhaps by functioning as a scaffold for separation of the active site of APC from the PL surface. PMID- 7794922 TI - Intracellular production of beta A4 amyloid of Alzheimer's disease: modulation by phosphoramidon and lack of coupling to the secretion of the amyloid precursor protein. AB - The amyloid precursor protein (APP) undergoes abnormal metabolism in Alzheimer's disease, resulting in the accumulation of beta A4 amyloid in the brain. Normal APP metabolism includes the release of a truncated form (sAPP) which has been cleaved at the alpha-secretase site within the beta A4 amyloidogenic domain. However, intact forms of beta A4 protein may also be generated by the beta- and gamma-secretases. Soluble forms of beta A4 have been detected in various cell lines and in cerebrospinal fluid. Previous studies of protein kinase C activation have suggested a reciprocal relationship between sAPP secretion and beta A4 production and release. We find that phorbol ester activation of protein kinase C in untransfected SH-SY5Y neuroblastoma cells increases the release of sAPP without affecting beta A4 secretion. We provide further evidence for intracellular beta A4 production. Treatment of SY5Y cells with the protease inhibitor phosphoramidon results in a 2-fold increase in beta A4 secretion and an increase in the amount of beta A4 recovered from cell lysates, yet it does not affect sAPP secretion. The protease inhibitors thiorphan and N-[(RS)-2-carboxy-3 phenylpropanoyl]-L-leucine had no effect on beta A4 or sAPP secretion. The lysosomotropic agents chloroquine and NH4Cl decreased beta A4 secretion, providing additional evidence for the involvement of intracellular acidic compartments in the production of beta A4. Our results therefore demonstrate a double dissociation between the secretion of sAPP and beta A4 in the SH-SY5Y cell line. The effect of phosphoramidon supports previous studies which show that metalloproteases are involved in the biogenesis of beta A4. PMID- 7794923 TI - Structural analysis of a novel interaction by calmodulin: high-affinity binding of a peptide in the absence of calcium. AB - The interaction of apocalmodulin (apoCaM) with a peptide (Neurop) based on the primary sequence of the calmodulin-binding domain of neuromodulin has been studied by nuclear magnetic resonance (NMR) methods. The NMR spectra of both apocalmodulin and its 1:1 complex with the Neurop peptide have been assigned by triple resonance and nuclear Overhauser effect-(NOE-) based strategies. ApoCaM displays many of the same basic structural features as calcium-saturated calmodulin. Analysis of observed chemical shifts and patterns of NOEs on the main chain indicates extensive and regular secondary structure throughout the N terminal domain. In contrast, the helices of the C-terminal domain are somewhat irregular and are dynamically averaged. The EF-hands are intact in the N-terminal domain with the loops forming a short antiparallel beta sheet. Under low-salt conditions, two helix-loop-helix EF-hand motifs are present in the C-terminal domain of apoCaM but do not show interstrand NOEs. The spectral perturbations of apoCaM upon complexation with the Neurop peptide are relatively small with the larger chemical shift perturbations occurring in the C-terminal domain. The general secondary structure and tertiary organization appears to remain roughly the same as in free apoCaM. Stoichiometric titration of the apoCaM.Neurop complex with calcium indicates that the C-terminal domain EF-hands have a higher affinity for calcium than N-terminal domain EF-hands. Thus, this complex offers a unique opportunity to examine the structural and energetic consequences of calcium dependent and calcium-independent binding of peptide to calmodulin. PMID- 7794924 TI - Minimum folding unit of dystrophin rod domain. AB - Fragments of the rod domain of dystrophin, which consists of spectrin-like repeating sequences, have been prepared by expression in Escherichia coli. The phasing established earlier for the dystrophin rod, as well as for Drosophila spectrin and smooth muscle alpha-actinin, suggested a length of less than 113 residues for the dystrophin repeat that we have chosen. Fragments with a common N terminus and lengths between 113 and 119 residues were prepared. The formation of the stable native tertiary fold could be recognized by resistance to proteolysis, the circular dichroism spectrum in the regions of both peptide and aromatic absorption bands and the resolution of the long-wavelength component in the tryptophan absorption spectrum. It was found that the critical length for folding was 117 residues: shortening the chain by 1 further residue resulted in loss of the capacity to form a defined tertiary structure. Residue 117 is a glutamine; replacement of this by a methionine residue did not impair the ability of the chain to enter the folded conformation, implying that it is the length of the C terminal alpha-helix, rather than any specific side-chain interaction, that is critical in determining the stability of the native structure. The fragment of 119 residues forms a significantly more stable structure than that of 117. It appears that the minimum unit capable of forming the native fold extends some residues into the adjoining sequence repeat. PMID- 7794925 TI - High resistance of Escherichia coli ribonuclease HI variant with quintuple thermostabilizing mutations to thermal denaturation, acid denaturation, and proteolytic degradation. AB - To test whether the combination of multiple thermostabilizing mutations is a useful strategy to generate a hyperstable mutant protein, five mutations, Gly23- >Ala, His62-->Pro, Val74-->Leu, Lys95-->Gly, and Asp134-->His or Asn, were simultaneously introduced into Escherichia coli ribonuclease HI. The enzymatic activities of the resultant quintuple mutant proteins, 5H- and 5N-RNases HI, which have His and Asn at position 134, respectively, were 35 and 55% of that of the wild-type protein. The far-UV and near-UV CD spectra of these mutant proteins were similar to those of the wild-type protein, suggesting that the mutations did not seriously affect the tertiary structure of the protein. The differences in the free energy change of unfolding between the wild-type and mutant proteins, delta delta G, were estimated by analyzing the thermal denaturation of the proteins by CD. The 5H-RNase HI protein, which was slightly more stable than the 5N-RNase HI, was more stable than the wild-type protein by 20.2 degrees C in Tm and 5.6 kcal/mol in delta G at pH 5.5. In addition, the 5H-RNase HI was highly resistant to proteolysis and acid denaturation. The effects of each mutation on the thermal stability and the susceptibility to chymotryptic digestion were nearly cumulative, and the 5H-RNase HI undergoes chymotryptic digestion at a rate that is 41 times slower than that of the wild-type protein. Good correlation was observed between the thermal stability and the resistance to chymotryptic digestion for all proteins examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794926 TI - Interaction between casein kinase II and the 90-kDa stress protein, HSP90. AB - Purified casein kinase II (CKII) aggregates and loses activity under physiological salt conditions and within the range of physiological temperatures. In accord with our previous report [Miyata, Y., & Yahara, I. (1992) J. Biol. Chem. 267, 7042-7047], we report here that HSP90 protects CKII from the aggregation and inactivation by forming soluble CKII-HSP90 complexes. Surface plasmon resonance (SPR) measurements revealed that CKII binds to immobilized HSP90 within minutes. The KD of the binding is approximately 10(-7) M. ATP does not influence the interaction. The membrane-overlay method revealed that HSP90 binds to the catalytic CKII alpha subunit. Heparin, which binds to CKII alpha, inhibited the binding of CKII to HSP90-Sepharose. In addition, HSP90 competed with DNA for binding to CKII. Finally, SPR experiments showed that a peptide corresponding to the heparin and DNA binding site of CKII alpha binds to immobilized HSP90. These results indicate that HSP90, DNA, and heparin compete with each other for binding to a common site of CKII alpha. If the binding of CKII to DNA is biologically significant, it could be possibly regulated also by HSP90. PMID- 7794927 TI - ENDOR studies of the primary donor cation radical in mutant reaction centers of Rhodobacter sphaeroides with altered hydrogen-bond interactions. AB - The electronic structure of the cation radical of the primary electron donor was investigated in genetically modified reaction centers of Rhodobacter sphaeroides. The site-directed mutations were designed to add or remove hydrogen bonds between the conjugated carbonyl groups of the primary donor, a bacteriochlorophyll dimer, and histidine residues of the protein and were introduced at the symmetry-related sites L168 His-->Phe, HF(L168), and M197 Phe-->His, FH(M197), near the 2-acetyl groups of the dimer and at sites M160 Leu-->His, LH(M160), and L131 Leu-->His, LH(L131), in the vicinity of the 9-keto carbonyls of the dimer. The single mutants and a complete set of double mutants were studied using EPR, ENDOR, and TRIPLE resonance spectroscopy. The changes in the hydrogen bond situation of the primary donor were accompanied by changes in the dimer oxidation midpoint potential, ranging from 410 to 710 mV in the investigated mutants [Lin, X., Murchison, H. A., Nagarajan, V., Parson, W. W., Williams, J. C. & Allen, J. P. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10265-10269]. It was found that the addition or removal of a hydrogen bond causes large shifts of the spin density between the two halves of the dimer. Measurements on double mutants showed that the unpaired electron can be gradually shifted from a localization on the L-half of the dimer to a localization on the M-half, depending on the hydrogen bond situation. As a control, the effects of the different hydrogen bonds on P.+ in the mutant HL(M202), which contains a BChlL-BPheM heterodimer as the primary donor with localized spin on the BChl aL [Bylina, E. J., & Youvan, D. C. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7226-7230; Schenck, C. C., Gaul, D., Steffen M., Boxer S. G., McDowell L., Kirmaier C., & Holten D. (1990) in Reaction Centers of Photosynthetic Bacteria (Michel-Beyerle M. E., Ed.) pp 229-238, Springer, Berlin] were studied. In this mutant only small local changes of the spin densities (< or = 10%) in the vicinity of the hydrogen bonds were observed. The effects of the introduced hydrogen bonds on the spin density distribution of the dimer in the mutants are discussed in terms of different orbital energies of the two BChl a moieties which are directly influenced by hydrogen bond formation. The observed changes of the spin density distribution for the double mutants are additive with respect to the single mutations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7794928 TI - EPR and ENDOR investigation of the primary electron acceptor radical anion QA.- in iron-depleted photosystem II membrane fragments. AB - Photosystem II (PS II) membrane fragments were treated with trypsin at pH = 7.4 followed by incubation with o-phenanthroline and lithium perchlorate. This procedure removes and/or decouples the non-heme Fe2+ associated with the quinones QA and QB in the PS II reaction center (RC). Treatment of such samples (referred to as iron-depleted) with sodium dithionite or illumination in the presence of dichlorophenol indophenol (DCIP) and sodium ascorbate yielded EPR spectra similar to those of the plastoquinone-9 (PQ-9) radical anion generated in organic solvents. Q-band EPR yielded the principal values of the g-tensor for PQ-9.- in 2 propanol and QA.- in PS II. Electron nuclear double resonance (ENDOR) experiments were performed both on PQ-9.- in vitro and on QA.- in the iron-depleted PS II samples. For the former a complete set of isotropic 1H hyperfine coupling constants and hyperfine tensors of the two methyl groups and the alpha-proton were obtained. On the basis of H/D exchange experiments two different hydrogen bonds could be detected in frozen solution that are formed between the carbonyl oxygens of the radical and protons from the surrounding solvent molecules. The hydrogen bond distances were estimated using the point-dipole model. 1H-ENDOR spectra of QA.- in iron-depleted PS II samples have been measured in buffers made in H2O and D2O. The spectrum in deuterated buffer allowed the determination of two different methyl group hyperfine tensors. Differences detected between the spectra in protonated and deuterated buffer reveal the hyperfine tensors of two exchangeable protons belonging to hydrogen bonds between the oxygens of QA and specific protein residues. The assignment of these hydrogen bonds in PS II is discussed and compared with the situation found in the bacterial reaction center. PMID- 7794929 TI - Spinach thylakoid polyphenol oxidase: cloning, characterization, and relation to a putative protein kinase. AB - A 64-kDa protein was purified from an octyl glucoside/cholate extract of spinach thylakoids. N-Terminal analysis yielded 23 residues of sequence, of which the first 15 were identical to a sequence reported [Gal, A., Herrmann, R. G., Lottspeich, F., & Ohad, I. (1992) FEBS Lett. 298, 33-35] for a protein kinase with specificity toward the photosystem II light-harvesting complex (LHC-II). We report the complete sequence of this 64-kDa protein, deduced from cDNA clones. The transit peptide has a chloroplast import signal at the N-terminus and a C terminal hydrophobic span bounded by basic amino acids that predicts localization of the protein to the thylakoid lumen. The mature protein sequence is about 50% identical to several polyphenol oxidases (PPOs). Canonical protein kinase motifs are absent, as are sequences characteristic of ATP-binding sites. The mature protein resembles arthropodan hemocyanin (Hc), possessing three major domains. The N-terminal domain is rich in cysteine residues and predicted alpha-helices. The central domain has a conserved motif, N-terminal to a presumptive Cu-A site, that is not found in tyrosinases or Hc and is proposed as the provider of a third imidazole ligand to Cu-A. An unusual 13-residue, glutamine-rich link begins a C terminal domain containing 7 predicted beta-strands which, by analogy with Hc, may form an antiparallel beta-barrel. We conclude that this 64-kDa polypeptide is a lumenal PPO and the precursor of a 42.5-kDa PPO form described previously [Golbeck, J. H., & Cammarata, K. V. (1981) Plant Physiol. 67, 977-984].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7794930 TI - Inhibition of in vitro transcription by a triplex-forming oligonucleotide targeted to human c-myc P2 promoter. AB - Triplex-forming oligonucleotides (TFOs) have been shown to bind in a sequence specific manner to polypurine/polypyrimidine sequences in several human gene promoters, including the c-myc P1 promoter. TFOs have been shown to inhibit transcription in vitro and the expression of target genes in cell culture. The human c-myc protooncogene contains a 23 base pair purine-pyrimidine-rich motif ( 62 to -40) within its predominant promoter, P2, that is a potential target for purine-purine-pyrimidine triplex formation. Using electrophoretic mobility shift analysis (EMSA) and competition experiments, we have demonstrated that a MAZ (myc associated zinc finger protein) consensus sequence is capable of competing with the purine-pyrimidine motif for the binding of a HeLa nuclear protein. We have shown the formation of an intermolecular triplex using a 23-base purine-rich oligonucleotide antiparallel to the purine-rich target sequence. DNase I footprinting was performed to confirm the exact location of triplex formation. Triplex formation by this oligonucleotide prevents binding of a HeLa nuclear protein (presumably MAZ) to the target site. We have also shown that the P2 targeted TFO is a potent and specific inhibitor of c-myc transcription in vitro. These data demonstrate that this novel TFO inhibits transcription of the c-myc P2 promoter. We propose that the P2-targeted TFO has its effect by blocking the binding of the regulatory factor MAZ. PMID- 7794931 TI - Peptide aldehyde inhibitors of hepatitis A virus 3C proteinase. AB - Picornaviral 3C proteinases are a group of closely related thiol proteinases responsible for processing of the viral polyprotein into its component proteins. These proteinases adopt a chymotrypsin-like fold [Allaire et al. (1994) Nature 369, 72-77; Matthews et al. (1994) Cell 77, 761-771] and a display an active-site configuration like those of the serine proteinases. Peptide-aldehydes based on the preferred peptide substrates for hepatitis A virus (HAV) 3C proteinase were synthesized by reduction of a thioester precursor. Acetyl-Leu-Ala-Ala-(N,N' dimethylglutaminal) was found to be a reversible, slow-binding inhibitor for HAV 3C with a Ki* of (4.2 +/- 0.8) x 10(-8) M. This inhibitor showed 50-fold less activity against the highly homologous human rhinovirus (strain 14) 3C proteinase, whose peptide substrate specificity is slightly different, suggesting a high degree of selectivity. NMR spectrometry of the adduct of the 13C-labeled inhibitor with the HAV-3C proteinase indicate that a thiohemiacetal is formed between the enzyme and the aldehyde carbon as previously noted for peptide aldehyde inhibitors of papain [Lewis & Wolfenden (1977) Biochemistry 16,4890 4894; Gamcsik et al. (1983) J. Am. Chem. Soc. 105, 6324-6325]. The adduct can also be observed by electrospray mass spectrometry. PMID- 7794932 TI - A single substitution in the motif 1 of Escherichia coli lysyl-tRNA synthetase induces cooperativity toward amino acid binding. AB - The constitutive lysyl-tRNA synthetase (LysRS) of the Escherichia coli strain OEL134 differs from the wild-type enzyme by the single substitution of threonine 208 with methionine. In vitro study of the isotopic [32P]PPi-ATP exchange reaction catalyzed by purified T208M LysRS revealed specific features that are not observed with the wild-type LysRS: (i) The steady state of the reaction was reached after a approximately 1-min lag when the addition of the enzyme was used to initiate the reaction. This lag disappeared upon preincubation of the enzyme with lysine and ATP. (ii) The variation of the steady state rate as a function of the lysine concentration in the assay was sigmoidal (Hill coefficient of 1.65), suggesting cooperativity of lysine binding to this dimeric enzyme. The allosteric behavior of the mutant enzyme was further established by showing that, at low concentrations of lysine, low amounts of cadaverine stimulated T208M LysRS activity. T208A LysRS, in which threonine 208 had been changed into alanine by site-directed mutagenesis, displayed the same properties as T208M LysRS. Remarkably, Thr 208 makes part of the first signature motif of class II aminoacyl tRNA synthetases, a motif likely to be involved in the dimerization of the enzyme subunits. Therefore, the behavior of the Thr 208 mutants of LysRS supports the idea that the dimerization of class II aminoacyl-tRNA synthetases is important for an efficient structuration of their active site. PMID- 7794933 TI - Mutation of arginine 276 to methionine changes Mg2+ cooperativity and the kinetic mechanism of fructose-1,6-bisphosphatase. AB - Arginine 276 of porcine liver fructose-1,6-bisphosphatase (FBPase) was mutated to methionine by site-directed mutagenesis on the basis of the crystal structure of the enzyme [Zhang, Y., Liang, J.-Y., Huang, S., Ke, H., & Lipscomb, W.N. (1993) Biochemistry 32, 1844-1857]. The mutant and wild-type forms of the enzyme were purified to homogeneity and characterized by circular dichroism spectrometry (CD) and initial-rate kinetics. There were no discernible differences between the secondary structures of the wild-type and the mutant enzymes on the basis of the CD data. Replacement of Arg 276 with methionine caused a significant decrease in the enzyme's activity. The kcat for the mutant enzyme was only about 0.67% of that of the wild-type enzyme. Most importantly, the mutation caused the total loss of cooperativity for Mg2+ and changed the kinetic mechanism to one in which the substrate adds to FBPase before Mg2+ and in which all steps equilibrate rapidly relative to the conversion of the ternary complex of enzyme, substrate, and Mg2+ to products. The Ka for Mg2+ increased by only about 5-fold relative to that of the wild-type enzyme. The mutation did not change the Ki for AMP or the Hill coefficient of this allosteric inhibitor. The Ki for fructose 2,6 bisphosphate was increased by 16-fold compared with that of the wild-type enzyme. The Km for fructose 1,6-bisphosphate was similar to that of the wild-type enzyme. It is concluded that Arg 276 is critical for activity and Mg2+ cooperativity with FBPase and it determines the enzyme's kinetic mechanism. PMID- 7794936 TI - Interpreting the effects of specific protein modification on antiport coupling mechanisms: the case of the aspartate/glutamate exchanger. AB - Reaction of two cysteine residues in the aspartate/glutamate carrier of mitochondria is reported to abolish exchange but to actuate a passive one-way exit of extremely low substrate affinity and specificity, but with the same activation energy as antiport (Dierks, T., Salentin, A. and Kramer, R. (1990) Biochim. Biophys. Acta 1028, 281-288). This behaviour, reminiscent of a channel, becomes understandable when the required control over carrier mobility by the substrate is allowed for. Whether the transport mechanism involves a substrate site alternately exposed on opposite sides of the membrane or sites simultaneously exposed on both sides, and whether the substrate acts by converting an immobile carrier conformation to an inherently mobile intermediate or by stabilizing the transition state in carrier movement, the same fundamental relationship emerges: the ratio of coupled to uncoupled rates (antiport relative to net flux) is limited by the ratio of substrate dissociation constants in successive carrier conformations, one immobile, the other mobile; the increment in the binding energy in the two forms must therefore be large. Shifts in the equilibrium between these conformations and shifts in their relative affinities for the substrate can account for the properties of the modified transport system, which, it is concluded, functions as a carrier, not a channel. PMID- 7794935 TI - Characterization of the human glucocorticoid receptor promoter. AB - To elucidate the functional elements that are involved in the regulation of the human glucocorticoid receptor (hGR) gene, transient expression, DNase I footprinting, and gel mobility shift analyses were conducted. We found that the hGR promoter region between -700 and +38 bp contained 11 footprinted sites. Deletion of the -374 to -183 bp region, which is highly conserved between human and mouse (93%), induced a 5-24-fold reduction in promoter activity in HeLa, NIH3T3, CV1, and HepG2 cells. Three footprints, FP5, FP6, and FP7, were shown to map to this region. In particular, the FP7 site was found to be within the -374 to -347 bp region. Deletion of this region triggered a significant decline in promoter activity in HeLa and NIH3T3 cells but not in HepG2 cells. AP2 was found to bind FP7. In HepG2 cells AP2 elicited transactivation of the hGR promoter activity. Transfection data revealed that the upstream GC box-rich fragment between -700 and -375 bp induced a 4-7-fold activation of the heterologous tk promoter in an orientation-independent manner. Our studies demonstrate that several transcription factors are involved in regulating GR expression and that AP2 could function as an important positive regulator of GR promoter activity. PMID- 7794934 TI - Conformational analysis of the xylose-containing N-glycan of pineapple stem bromelain as part of the intact glycoprotein. AB - The conformational behavior of the N-glycan Man alpha 1-6(Xyl beta 1-2)Man beta 1 4GlcNAc beta 1-4(Fuc alpha 1-3)GlcNAc beta of stem bromelain as part of the intact glycoprotein was investigated and compared with that of the same N-glycan as part of a bromelain-derived glycopeptide. Proton chemical shifts of the glycoprotein N-glycan were determined by 2D HOHAHA and 2D NOESY measurements, making use of the glycopeptide 1H NMR data. During each 2D NMR experiment about 4% of the glycoprotein denatured. Experimental data concerning interproton distances of the intact glycoprotein N-glycan were obtained by NOESY 1H NMR spectroscopy. Several theoretical models for the N-glycan, obtained by molecular dynamics simulations of the glycopeptide, were investigated. Comparison of experimental and theoretical NOESY cross peak intensities was performed with the program CROSREL. In comparison with the glycopeptide, the distribution of populations between two main conformations of the Fuc alpha 1-3GlcNAc linkage was altered. In addition, the omega = 60 degrees (gt) rotamer of the Man alpha 1-6Man linkage seems to be present for a significant period of time, whereas in the glycopeptide the omega = -60 degrees (gg) conformation exists exclusively. Except for the Xyl beta 1-2Man linkage, the mobilities around the glycosidic linkages in the glycoprotein were reduced compared with those in the glycopeptide, especially concerning the Fuc alpha 1-3GlcNAc and Man alpha 1-6Man linkages. These findings might be the result of an interaction of the polypeptide chain with the Fuc alpha/Man alpha side of the N-glycan. A qualitative analysis of the NMR spectra showed a larger degree of mobility in the denatured glycoprotein N-glycan than in the intact glycoprotein. PMID- 7794937 TI - Preferential association of membrane phospholipids with the human erythrocyte hexose transporter. AB - This study reports the results of an investigation to determine to what extent the influence of membrane lipids on the human erythrocyte sugar transporter protein activity (Caruthers, A. and Melchior, D.L. (1988) Annu. Rev. Physiol. 50, 257-271) is related to lipid/protein associations in the membrane bilayer. Differential scanning calorimetry was carried out on the human erythrocyte transport protein reconstituted into artificial bilayers formed from preselected lipids. it was found that the transport protein displays a preferential and in some cases strongly preferential affinity for specific lipid types. This association is a function of lipid head group, backbone and hydrocarbon chain length. It appears that the affinity of the transport protein for various lipids can correlate with the lipid's ability to influence transporter activity. This study further suggests that certain lipids (in this case sphingomyelin) can induce an oligomeric association of HEST monomers in the bilayer. PMID- 7794938 TI - Structural interactions between alpha- and beta-subunits of the gastric H,K ATPase. AB - Structural and functional interactions between alpha- and beta-subunits of the H,K-ATPase were explored. The sensitivity to trypsinolysis of alpha-subunit was monitored by SDS-PAGE in control H,K-ATPase-enriched microsomes and in microsomes in which disulfide bonds of the beta-subunit were reduced using 2-mercaptoethanol (2-ME). Reduction of beta-subunit disulfide bonds increased the susceptibility of the alpha-subunit to tryptic digestion. Kinetics of trypsinolysis were also carried out in the presence of ligands known to bind with H,K-ATPase and favor a particular conformer state in the native enzyme. The time-course for release of tryptic peptides was monitored in protein stained gels and Western blots probed with monoclonal antibody alpha-H,K,12.18. In control preparations, where beta subunit disulfides remained intact, trypsinolysis in the presence of ATP or K+ produced distinctive patterns of tryptic fragments, each characteristic of the conformational states induced by the respective ligand. For 2-ME-treated microsomes the altered alpha-subunit was unable to undergo ligand-induced conformational changes. The increased susceptibility of the alpha-subunit to trypsinization, the change in accessibility of tryptic cleavage sites and the inability of the alpha-subunit to undergo ligand-induced conformational changes after reduction of the beta-subunit disulfides suggest that the interactions between alpha- and beta-subunits are important for the conformational stability of the functional holoenzyme. A model localizing the most susceptible tryptic cleavage sites in control and 2-ME-reduced states is presented. PMID- 7794940 TI - Characterisation of endoplasmic reticulum and plasma membrane Ca(2+)-ATPases in pancreatic beta-cells and in islets of Langerhans. AB - We have investigated the plasma membrane (PMCA) and endoplasmic reticulum (SERCA) Ca(2+)-ATPases involved in active transport of Ca2+ in pancreatic beta-cell lines (MIN6, HIT T15, RINm5F) and in islets of Langerhans. Under selective membrane phosphorylation conditions (at low ATP concentration, in the presence of Ca2+ and La3+ and in the absence of Mg2+ at 4 degrees C) the only labelled proteins are the phosphoenzyme intermediates of the Ca(2+)-ATPases. Under these conditions, beta-cell membranes incorporated 32P from [gamma-32P]ATP into two proteins with molecular mass on acidic SDS-polyacrylamide gels of around 115 and 150 kDa. The 150 kDa band was identified as PMCA (i) by reaction with a monoclonal anti-human erythrocyte plasma membrane Ca(2+)-ATPase antibody; (ii) by its typical tryptic cleavage pattern which generated an 80 kDa band; (iii) by lack of inhibition of its autophosphorylation by SERCA-specific inhibitors. The 115 kDa band was identified as SERCA (i) by reaction with a polyclonal anti-rat fast skeletal muscle Ca(2+)-ATPase antibody; (ii) by the concentration-dependent inhibition of its autophosphorylation by thapsigargin and 2,5-di(t-butyl)-1,4-benzohydroquinone (tBHQ), which are specific inhibitors of SERCA. The 115 kDa band was further characterised as the SERCA-2b isoform by reaction with a polyclonal rabbit antibody against the 12 C-terminal amino acids of SERCA-2b. PMID- 7794939 TI - Heme as an optical probe for studying the interactions between calmodulin and the Ca(2+)-ATPase of the human erythrocyte membrane. AB - The heme group was used as an optical probe to study the interactions between calmodulin and its targets: the peptide melittin and the enzyme Ca(2+)-ATPase. As already reported, melittin when present in Tris buffer binds hemin-CN which quenches the tryptophan fluorescence. Addition of calmodulin restores the fluorescence significantly accompanied by a blue shift. We show here that the recovery of fluorescence is very slow and takes about 120 min to become constant. In a hydrophobic buffer, the fluorescence spectrum of melittin is already shifted with a peak at 335 nm and intensity almost 2-fold relative to a similar concentration of melittin in Tris buffer. The quenching of tryptophan fluorescence is lesser in this buffer and further addition of calmodulin fails to restore the fluorescence. This indicates the absence of binding of calmodulin to melittin in hydrophobic conditions. Under similar conditions of hydrophobicity, hemin-CN quenches about 35% of the tryptophan fluorescence of the Ca(2+)-ATPase. The subsequent addition of calmodulin restores about half of the quenched fluorescence. The interaction of calmodulin with the Ca(2+)-ATPase even under hydrophobic conditions suggests its high specificity for the enzyme which may be expected for a physiological target. PMID- 7794941 TI - Relation between membrane fluidity and signal transduction in the human megakaryoblastic cell line MEG-01. AB - The fluidity of the plasma membrane is thought to affect the responsiveness of blood platelets. We measured membrane fluidity in a single cell by Fluorescence Recovery after Photobleaching (FRAP) of the lipophilic probe DiIC14. Since platelets are too small for this technique, we used the human megakaryoblastic cell-line MEG-01, which shares many properties with platelets. MEG-01 cells were cultured for 44 h with simvastatin or mevalonate to change the cholesterol content, enabling analysis of signal processing at cholesterol/phospholipid ratios (C/P) between 0.20 and 0.31. The diffusion of DiIC14 correlated inversely with the C/P ratio with lateral diffusion coefficients (D) of 3.28 x 10(-9) cm2/s at a low C/P decreasing to 2.55 x 10(-9) cm2/s at a high C/P ratio. The mobile fraction was 65% and constant at the different C/P ratios. The relation between lipid diffusion and signal processing was measured following stimulation with 10 U/ml thrombin at 22 degrees C. There were only little differences in phosphatidylinositol metabolism, Ca2+ influx or mobilization and prostaglandin I2 induced formation of cyclic AMP. At 37 degrees C, cells with a high C/P ratio showed increased phosphatidylinositol metabolism, but these differences had no major effect on the Ca2+ responses. These data demonstrate that in megakaryoblasts the lateral diffusion of lipids is inversely correlated with the C/P ratio, but within the range of 0.20-0.31 the influence on signal processing is minor. PMID- 7794943 TI - Uptake and passage of beta-lactoglobulin, palmitic acid and retinol across the Caco-2 monolayer. AB - Caco-2 cell line grown on collagen coated polycarbonate membranes in bicameral chambers has been used to study the effect of the binding of palmitic acid or retinol on the uptake and passage of iodinated beta-lactoglobulin and albumin across cell monolayers. The percentage of beta-lactoglobulin transported through the monolayer was higher than that of albumin, about 50% and 30% of the total protein after 24 h of incubation, respectively. In all cases, less than 1% of protein was retained intracellularly. No differences were found in the uptake and transport of beta-lactoglobulin or albumin in the presence or absence of ligands. Furthermore, uptake and passage across Caco-2 monolayer of retinol or palmitic acid added either bound to beta-lactoglobulin or to albumin have been compared. The percentage of retinol found in the lower chamber was about 35% of the total retinol after 24 h of incubation for both proteins. However, the amount of retinol associated to cells was higher when it was added bound to beta lactoglobulin than to albumin, about 26% and 10%, respectively. This fact suggests that the metabolic processing of retinol by Caco-2 cells is the rate limiting step for retinol transport. The percentage of palmitic acid that crossed the monolayer was about 7%, remaining approx. 90% in the cells for beta lactoglobulin and albumin. These data support the hypothesis that palmitic acid internalized by Caco-2 cells is mainly destined to serve the structural and energy needs. These results show evidence of retinol and palmitic uptake by Caco 2 cells when beta-lactoglobulin or albumin are the donors, and indicate that the type of binding protein does not affect the transport of both ligands through Caco-2 monolayer. PMID- 7794942 TI - Adenine nucleotide binding and photoincorporation in Glanzmann's thrombasthenia platelets. AB - Adenosine 5'-(1-thiotriphosphate) (ATP alpha S) binds to about 25,000 high affinity sites in platelets (Kd approximately 3 nM), competes fully in inhibiting the binding of ADP and, despite the absence of a specific photoactivatable substituent, is directly photoincorporated into a specific 18 kDa domain beginning at Tyr-198 in the alpha chain of glycoprotein IIb (GPIIb alpha) following ultraviolet irradiation of fresh unfixed platelets (Greco et al. (1991) J. Biol. Chem. 266, 13627-13633). 8-azido ATP has now been shown to have similar binding parameters (Kd 8 nM, 20,000 sites/platelet) but, in this case, photoincorporation occurred equally in GPIIb and GPIIIa. To determine the possible function of GPIIb alpha in ADP-induced activation, platelets were isolated from two Glanzmann's thrombasthenia patients whose platelets contain approximately 6% of normal levels of GPIIb. ADP and ATP alpha S bound to intact, formaldehyde-fixed Glanzmann's platelets at high affinity sites with dissociation constants of approximately 30 nM and approximately 2 nM, respectively. Both nucleotides also bound to low affinity sites with dissociation constants of approximately 2 microM: these values are similar to those obtained with control platelets. ATP alpha S antagonized the shape ADP-induced shape change response of Glanzmann's platelets (EC50 5 microM) indicating that it bound to the P2T (ADP) receptor. However, photoincorporation was low (approximately 7% of control) similar to their content of GPIIb alpha. These results show that ADP binding and photoincorporation are occurring at different sites on the platelet surface but suggest that the ADP binding site may be located in proximity to GPIIb alpha. PMID- 7794945 TI - Collateral sensitivity of multidrug resistant cells to narcotic analgesics is due to effects on the plasma membrane. AB - It has previously been demonstrated that opiates interact directly with P glycoprotein in drug resistant Chinese hamster ovary (CHO) cells (Callaghan, R. and Riordan, J.R. (1993) J. Biol. Chem. 268, 16059-16064). In this study we have examined the effects of several opiates on the growth of drug sensitive and resistant CHO and human MCF7 cell lines. The growth of P-glycoprotein expressing cells was inhibited by the opiates pentazocine, pethidine and naloxone to a greater extent than in drug sensitive cells. Since P-glycoprotein is localised at the plasma membrane the effects of opiates on membrane biophysical properties were investigated. The opiates caused a fluidizing effect in membranes from P glycoprotein expressing cells and decreased the basal level of P-glycoprotein phosphorylation. In addition, they were able to increase the leakage of the membrane impermeant compound 6-carboxyfluorescein entrapped in model membrane vesicles. The ability to alter membrane biophysical properties correlated with the inhibitory effects on growth of drug resistant cells. These results suggest that the collateral sensitivity of P-glycoprotein expressing cell lines to opiates is mediated by the drugs' effects on the plasma membrane. PMID- 7794944 TI - Sodium-independent carrier-mediated inositol transport in cultured renal epithelial (LLC-PK1) cells. AB - In addition to the concentrative, Na(+)-dependent inositol transport system demonstrated in many cell types, carrier-mediated, Na(+)-independent inositol transport is also shown to exist in LLC-PK1 renal epithelia. Inhibition of inositol uptake in Na(+)-free saline by 0.1 mM phloretin, and self-inhibition by net concentrations of inositol exceeding 10 mM, demonstrate the carrier-mediation of the Na(+)-independent uptake and distinguish it from flux through anion channels. The Na(+)-dependent uptake exhibits higher affinity for inositol, as seen by the stronger self-inhibition at lower inositol concentrations in Na+ saline. Kinetic analyses indicate a Km of 178 microM and a Vmax of 2447 pmol/min per microgram DNA for the Na(+)-dependent system, whereas the lower affinity, lower capacity Na(+)-independent system manifests a Km of 5.2 mM and a Vmax of 249 pmol/min per microgram DNA. the Na(+)-independent uptake further differs from the Na(+)-dependent transport by the lack of inhibitory effect of 10 microM glucose, and the greater relative inhibition of phloretin compared to that of phlorizin. Both types of uptake appear to localize predominantly to the basal lateral cell surface. The Na(+)-independent transport is bidirectional, functioning in efflux as well as influx of inositol. PMID- 7794946 TI - Proliferation of intracellular membrane structures upon homologous overproduction of cytochrome P-450 in Candida maltosa. AB - In an alkane-assimilating yeast, Candida maltosa, a cultivation on alkane causes both induction of endoplasmic reticulum (ER)-resident membrane proteins, such as cytochrome P-450, and proliferation of ER. In this study, individual genes for alkane-inducible forms of cytochrome P-450 (P-450alk) were homologously overexpressed in C. maltosa using a galactose-inducible expression system developed in this yeast. Immunoelectron microscopy revealed that, upon the overexpression, a dramatic proliferation of ER occurred, in which overproduced P 450alk protein accumulated. The proliferated membranes were mainly tubular forms and stacks of paired membranes were also observed after prolonged expression. The tubular forms were morphologically very similar to the proliferated ER in alkane induced C. maltosa cells. The observed proliferation of ER membranes by homologous overproduction of P-450alk, here depicted, will provide a unique opportunity for investigating the mechanisms by which cells regulate ER biogenesis, in comparison with the intrinsic form of ER proliferation. PMID- 7794947 TI - Effect of the modifications of ionizable groups of amphotericin B on its ability to form complexes with sterols in hydroalcoholic media. AB - The interaction of amphotericin B and some of its semisynthetic derivatives with cholesterol and ergosterol has been tested in 1:4 (v/v) ethanol/water mixture by circular dichroism and absorption spectroscopy. The effect of the chemical modification of the 'ionizable head' of the antibiotic, the pH of the medium, and the sterol/antibiotic ratio has been studied. The results obtained show that in the presence of the sterols, amphotericin B forms several spectroscopically different species. A high extent of polyene-sterol interaction is observed for: (i) amphotericin B in neutral or acidic media, (ii) esters and amides at neutral or alkaline media, (iii) N-acyl derivatives only in acidic medium. The extent of interaction at neutral pH is highly correlated with the biological activity of compounds tested. The implication of these findings on the nature of the forces responsible for the antibiotic-sterol interaction is discussed. PMID- 7794948 TI - Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory. AB - The technique of fluorescence recovery after photobleaching was used to measure the lateral mobility of membrane integral proteins in reticulocyte plasma membranes which were treated to modify the 'fluid' lipid or immobilized protein fractions, hence increasing the relative prevalence of obstacles to protein lateral motion. This was achieved by either: (1) treating the plasma membranes with phospholipase A2 followed by extraction of the hydrolysis products using fatty-acid-free bovine serum albumin, resulting in a decrease in the membrane 'fluid' lipid portion; or (2) preincubating the plasma membranes with polylysines, resulting in plasma membrane protein aggregation and immobilization. As the prevalence of obstacles to lateral motion increased in plasma membranes through the treatments described above, the mobility of the membrane integral proteins diminished. Experimental results for the dependence of protein mobility on the prevalence of obstacles to lateral motion were compared to theoretical data in order to verify the applicability of the percolation theory to reticulocyte plasma membranes. The influence of a decrease in the 'fluid' lipid and an increase in the immobilized membrane protein fractions upon the hormone stimulated adenylate cyclase activity has been studied as well. As the 'solid' lipid and immobilized membrane protein fractions decreased, both the hormone stimulated adenylate cyclase activity and the fraction of beta-adrenergic receptors with high affinity to hormone diminished. It was shown that this correlation can be caused by a decrease in membrane fraction accessible to the movement of the interacting proteins of the adenylate cyclase complex. Hormonal stimulation of adenylate cyclase is discussed in terms of the percolation theory. PMID- 7794950 TI - Species differences in 5-HT2A receptors: cloned pig and rhesus monkey 5-HT2A receptors reveal conserved transmembrane homology to the human rather than rat sequence. AB - Pig and rhesus monkey 5-HT2A receptor cDNA clones were isolated. The pig and rhesus monkey clones encode proteins that share a 94% and 95% homology, respectively, with the rat 5-HT2A receptor, and a 97% and > 99% homology, respectively, with the human 5-HT2A receptor. Within the transmembrane regions of the pig and monkey receptors, the deduced amino acid shows only three differences compared to that of the rat and are identical to the human 5-HT2A receptor clone. PMID- 7794949 TI - Calcium ions and interactions of pulmonary surfactant proteins SP-B and SP-C with phospholipids in spread monolayers at the air/water interface. AB - Spread monolayers containing hydrophobic pulmonary surfactant protein, SP-B or SP C, or SP-B/SP-C (2:1, w/w), alone or mixed with dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG), were formed on saline subphases containing calcium ions. Surface pressure-area characteristics of the films of the proteins were not affected by the presence of Ca2+ in the subphase. Calcium ions did not alter the surface properties of the binary and ternary films of DPPC plus either SP-B, or SP-C, or SP-B/SP-C (2:1, w/w). Surface pressure-area isotherms for the spread films of DPPG plus hydrophobic surfactant protein were Ca(2+)-dependent. The exclusion pressures of SP-B, SP-C and SP-B/SP-C (2:1, w/w) from protein-DPPG films in the presence of calcium were lower than the exclusion pressures in the absence of Ca2+. The divalent cation appeared to suppress the ability of SP-C and SP-B/SP-C (2:1, w/w) to remove phospholipid during squeeze out from their mixed films with DPPG. The effects of Ca2+ on the monolayers of DPPG plus hydrophobic surfactant proteins were consistent with calcium producing diminished lipid-protein interactions, possibly resulting from Ca(2+)-induced changes in the ionization state and molecular packing of DPPG. PMID- 7794952 TI - Evidence for an essential histidine residue located in the binding site of the cysteine-specific lysosomal transport protein. AB - Previously, we observed that the activity of the cysteine-specific lysosomal transport system increases 7-10-fold between pH 6 and 7.3 to be maximally active in the neutral pH range. To understand what factors contribute to this pH dependence, different chemical modifying agents were used to probe the nature of amino acid residues residing in the transport protein binding site. Diethyl pyrocarbonate (1 mM) and N-ethylmaleimide (5 mM) each strongly inactivated lysosomal cysteine uptake > or = 88%, whereas dicyclohexyl-carbodiimide (2.5 mM), phenylisothiocyanate (2 mM), N-acetylimidazole (33 mM), and phenylglyoxal (2 mM) had a moderate to small effect. Maximal inactivation by DEPC occurs within 12-15 min upon exposure to DEPC concentrations > or = 1 mM. DEPC inactivation is consistent with modification of a histidine residue, displaying no inactivation at pH < 6, half-maximal inactivation at pH 6.6, and maximal inactivation at pH > or = 7.3. The close correspondence of DEPC inactivation to the pH activity curve of cysteine uptake suggests the large increase in lysosomal cysteine transport activity between pH 6 and 7.3 reflects deprotonation of an essential histidine residue. The substrate, L-cysteine (4 mM), fully protects the transport protein from DEPC inactivation suggesting that this histidine residue is located in the carrier's substrate binding site. Finally, part of the pH dependence of the lysosomal cysteine carrier appears to be due to responsiveness to the lysosomal transmembrane proton gradient as indicated by lysosomal membrane vesicles which display a 1.5-fold greater rate of cysteine uptake when pH 7.4out > pH 5.3in than when pH 7.4out = pH 7.4in. PMID- 7794951 TI - Cloning of an organ of Corti anion exchanger 2 isoform with a truncated C terminal domain. AB - We have isolated a cDNA clone from a guinea pig organ of Corti library encoding a new isoform of the Anion Exchanger 2 (AE2) protein. This cDNA clone shows an 83 bp deletion in the region that encodes the membrane domain of AE2. Analysis of the overlapping regions of genomic and cDNA clones indicates that the missing portion does not correspond exactly to a constitutive exon. The alternate splicing process that generates this transcript involves internal donor and acceptor sites which introduces a shift in the open reading frame. The resulting polypeptide has a conserved cytoplasmic N-terminal domain but the membrane C terminal domain has only two of the fourteen membrane spanning regions. An affinity-purified antipeptide antibody to the novel C-terminus detects an 89 kDa polypeptide which agrees with the molecular mass predicted from the cDNA. PMID- 7794953 TI - Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors: enalapril, enalaprilat, and lisinopril. AB - The affinity of three substrates for the intestinal peptide carrier is explained based on their three-dimensional (3D) structural data. The kinetic transport parameters of three ACE-inhibitors, enalapril, enalaprilat, and lisinopril, have been determined in an in vivo system using rat intestine. The observed kinetic transport parameters (+/- asymptotic standard error) of enalapril are: 0.81 (+/- 0.23) mM, 0.58 (+/- 0.37) mumol/h per cm2, and 0.56 (+/- 0.04) cm/h for the half maximal transport concentration (KT), the maximal transport flux (Jmax) and the passive permeability constant (Pm). Enalaprilat was transported by passive diffusional with a Pm of 0.51 (+/- 0.04) cm/h. For lisinopril the kinetic transport parameters were 0.38 (+/- 0.19) mM, 0.12 (+/- 0.07) mumol/h per cm2, and 0.18 (+/- 0.02) cm/h for KT, Jmax, and Pm, respectively. The affinity of the ACE-inhibitors for the intestinal peptide carrier has been evaluated based on their ability to inhibit the transport rate of cephalexin. The inhibition constants (Ki) of enalapril, enalaprilat and lisinopril were 0.15, 0.28 and 0.39 mM, respectively. 3D structural analysis of lisinopril using molecular modelling techniques reveals that intramolecular hydrogen bond formation is responsible for decreased carrier affinity. PMID- 7794954 TI - Docosahexaenoic acid-induced alteration of Thy-1 and CD8 expression on murine splenocytes. AB - Here we test whether the incorporation of docosahexaenoic acid (DHA, 22:6), an (n 3) fatty acid, into lymphocyte membranes affects the expression of the surface proteins Thy-1.2 and CD8. DHA was incorporated into splenocytes by three methods: feeding mice diets containing menhaden (fish) oil, fusing splenocytes with DHA containing phosphatidylcholine vesicles, and culturing splenocytes with DHA. Thy 1.2 and CD8 expression were measured by flow cytometry and complement-mediated lysis using a panel of monoclonal antibodies. As (n-3) fatty acid incorporation into the lymphocytes increased, the expression of one Thy-1.2 epitope and one CD8 epitope decreased; the expression of two CD8 epitopes increased. Although diet induced changes in surface protein expression may result from selective migration of cell populations or the diet's effect on protein biosynthesis, fusion with lipid vesicles demonstrated that DHA-containing phospholipids can mediate a direct and immediate effect. The decrease in Thy-1.2 expression was sustained for more than a week after removal of (n-3) fatty acids from the diet, most likely due to retention of membrane-bound (n-3) fatty acids. Because Thy-1.2 and CD8 participate in T cell activation, modulation of their expression by DHA suggests that DHA, when serving as a membrane structural element, may alter immune function. PMID- 7794955 TI - Oleic acid uptake into rat and rabbit jejunal brush border membrane. AB - Oleic acid uptake was studied using adult rabbit and rat jejunal brush border membrane vesicles. There was a reduction of oleic acid uptake following trypsin treatment. Opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. The addition of mucin further increased the enhanced uptake of oleic acid observed in the presence of opposing Na+/H+ gradients. Amiloride, an inhibitor of the Na+/H+ exchanger, reduced by about 40% the uptake of oleic acid into sheets of rat jejunum, and this inhibitory effect was observed over a range of rates of stirring of the bulk phase. In rabbit jejunal brush border membrane vesicles, amiloride reduced oleic acid uptake in the presence but not in the absence of opposing Na+/H+ gradients, with a Ki of approx. 36 microM. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, influenced by a process which involves the activation of the brush border membrane Na+/H+ exchanger. PMID- 7794956 TI - Lamellar-phase polymorphism in interdigitated bilayer assemblies. AB - Bilayers composed of 1-octadecanoyl-2-decanoyl-sn-glycero-3-phosphocholine (C(18)C(10)PC) adopt a mixed-interdigitated gel-phase packing where the short chains of the C(18)C(10)PC molecules pack end-to-end while their long chains span the entire hydrocarbon width of the bilayer. Calorimetric cooling scans of freshly prepared hand-shaken bilayer suspensions of C(18)C(10)PC exhibit a single exothermic phase transition at 14.6 degrees C, whereas suspensions incubated at temperatures below 2 degrees C for several days exhibit an additional phase transition exotherm at 17.9 degrees C. Calorimetric and electron microscopic evidence is presented that low-temperature incubation of C(18)C(10)PC bilayer suspensions composed of liposomes of heterogeneous size leads to the conversion of those liposomes in the suspension below about 0.2 microns in diameter into planar lamellar sheets. These lamellar sheets are the origin of the phase transition exotherm at 17.9 degrees C, whereas the phase-transition exotherm at 14.6 degrees C arises from the liposomes in the suspension. We also show that phosphatidylcholine bilayer suspensions, induced to interdigitate by ethanol, exhibit a similar thermotropic behavior. The implication of these findings for the reversibility of interdigitated gel to liquid-crystalline phase transitions and the role of phospholipid molecular geometry in the formation of interdigitated bilayers are addressed. PMID- 7794957 TI - Interaction of free fatty acids with phospholipid bilayers. AB - The partition of free fatty acids (FFA) to egg-phosphatidylcholine (egg-PC) and egg-phosphatidylethanolamine (egg-PE) vesicles was studied. Upon the addition of FFA to the suspension of vesicles, the pH of the aqueous phase changed depending on the length and saturation of the FFA hydrocarbon chain, as well as on the vesicle composition. The medium pH decreased faster if FFA was added to egg-PE as compared to egg-PC vesicles. The fluorescent free fatty acid indicator (ADIFAB) was used to measure the amount of FFA remaining in the aqueous phase. Most of the FFA added to the suspension of egg-PE vesicles remained in the aqueous phase, whereas in the presence of egg-PC vesicles the FFA partitioned preferentially into the lipid phase. The amount of FFA incorporated into the lipid bilayers was estimated by measuring the changes of pH at the lipid bilayer surface, using fluorescein-PE. At high surface concentrations of FFA, decreasing pH at the bilayer surface caused the protonation of FFA, and raised the pK of FFA at the bilayer surface from 5 to about 7. The partition of FFA in egg-PE vesicles was an order of magnitude lower than that in egg-PC vesicles. The incorporation amount was determined more by the molecular packing than by the nature of lipid headgroups, because steroylcaprioyl-PE, which preferred the bilayer structure, behaved more like egg-PC than egg-PE. Understanding FFA partition characteristics would help to interpret the hydrolysis measurements of phospholipids, and to explain many biological activities of FFA. PMID- 7794958 TI - The effect of protoporphyrin on the susceptibility of human erythrocytes to oxidative stress: exposure to hydrogen peroxide. AB - Binding of protoporphyrin caused a perturbation of the erythrocyte membrane, as reflected by a change in cell shape from discoid to echinocyte, and a concomitant increase in mean cellular volume and K(+)-loss. Protoporphyrin-induced changes could be prevented by the presence of BaCl2, whereas binding of protoporphyrin was not affected. Exposure of erythrocytes to hydrogen peroxide leads to K(+) leakage and lipid peroxidation. In de presence of protoporphyrin, H2O2-induced K(+)-leakage was enhanced, whereas lipid peroxidation was inhibited. The increase in H2O2-induced K(+)-leakage by protoporphyrin was not affected by diamide or various K+ channel blockers, but could be prevented by the addition of BaCl2. The inhibition of lipid peroxidation, on the other hand, was not affected by BaCl2. These results indicate that the enhancement of H2O2-induced K(+)-leakage was most likely caused by the change in cell shape. Addition of chlorpromazine and promethazine, positively charged molecules that induce stomatocytosis, did not cause an enhancement of H2O2-induced K(+)-leakage. PMID- 7794959 TI - Reconstitution of the Neurospora crassa plasma membrane H(+)-adenosine triphosphatase. AB - The purified H(+)-ATPase of the Neurospora crassa plasma membrane has been reconstituted by a gel filtration method into lipidic vesicles using sodium deoxycholate as the detergent. Reconstitution was performed for lipid/ATPase ratios ranging from 1000:1 to 5:1 (w/w). Whatever the lipid/ATPase ratio, the ATPase molecules completely associate with the lipid vesicles. The ATPase specific activity is identical for all proteoliposomes regardless of the lipid/ATPase ratio, but the H+ transport decreases at high protein/lipid ratios, suggesting that the proteoliposomes are more leaky to H+ as the amount of protein inserted into the lipidic membrane increases. Analysis of the fragments generated by trypsin proteolysis in the presence and in the absence of MgATP+ vanadate indicate that most of the reconstituted ATPase molecules are able to assume the transition state of the enzyme dephosphorylation reaction, and are therefore functional. The orientation (inside-out or rightside-out) of the ATPase molecules in the vesicles is independent of the lipid/ATPase ratio chosen for the reconstitution. For all the lipid/ATPase ratios tested, most of the ATPase molecules (> 99%) expose their cytoplasmic side to the outside of the reconstituted proteoliposomes. The size of the vesicles increases parallel to the ATPase amount. Although the H+ leakiness of our preparation at low lipid/protein ratios prevents proton pumping measurements, the reconstitution procedure described here has the main advantage on other procedures to allow the obtention of vesicles at high protein-to-lipid ratios, facilitating further structural characterization of the ATPase by biochemical and biophysical techniques. Therefore, the procedure described here could be of general interest in the field of membrane protein study. PMID- 7794961 TI - Dispersion state of phospholipids and fluorescence production with peroxidation in organic solvents: investigated by time-resolved fluorescence technique. AB - Fluorescent substances were found to be produced efficiently when phospholipids containing phosphatidylethanolamine (PE) and linoleic chains were autoxidized in non-polar solvents. By using these fluorescent substances as intrinsic probes, the dispersion state of phospholipids was investigated in various organic solvents. Fluorescence anisotropy decay measurements indicated that the aggregation size of phospholipids was much larger in hexane than in chloroform, methanol and tert-butyl alcohol. The average diameter of phospholipid aggregates in hexane was calculated to be 4-6 nm, which was dependent on the lipid composition. A consistent result was obtained when N-(7-nitrobenz-2-oxa-1,3 diazol-4-yl)-1,2-dihexadecanoyl-sn-gly cer o-3- phosphoethanolamine (NBD-PE) was used as an extrinsic probe. Comparison of the fluorescence data with small-angle X-ray scattering (SAXS) data suggested that a reverse micellar structure of phospholipids formed in hexane. It was shown that phospholipid aggregation enhanced the extent of peroxidation as well as the production yield of fluorescent substances of phospholipid. PMID- 7794960 TI - Correct oligomerization is a prerequisite for insertion of the central molecular domain of staphylococcal alpha-toxin into the lipid bilayer. AB - Staphylococcal alpha-toxin is a primarily hydrophilic molecule that binds as a monomer to target membranes and then aggregates to form amphiphilic oligomers that represent water-filled transmembrane channels. Current evidence indicates that a region located in the center of the molecule inserts deeply into the bilayer. In the present study, we sought to determine whether membrane insertion was triggered by the oligomerization process, and whether insertion correlated with pore formation. Double mutants of alpha-toxin were prepared in which His-35 was replaced by Arg, and cysteine residues were introduced at positions 69, 130 and 186. Substitution of His-35 with Arg rendered the toxin molecules incapable of proper oligomerization, so that they remained in nonlytic form after binding to membranes. The sulfhydryl groups were labelled with the polarity-sensitive fluorescent dye acrylodan. Functionally intact, single mutant toxins containing only the cysteine residues were utilized as controls. Measurements of the fluorescence emission spectrum of acrylodan were performed for the active and inactive alpha-toxin mutants in free solution and in membrane-bound form. The collective results demonstrate that proper oligomerization is required for membrane insertion of the central region in the alpha-toxin molecule, and that lack of insertion correlates with absence of pore formation. PMID- 7794962 TI - Identification of antitumor sulfonylurea binding proteins of HeLa plasma membranes. AB - Plasma membranes of cultured HeLa S cells bound the tritiated antitumor sulfonylurea [3H]LY181984 with high affinity (Kd of about 25 nM). The number of binding sites, estimated to represent 30 to 35 pmol/mg protein, would represent a low abundance protein of the total plasma membrane proteins. The binding proteins appeared to contain one or more thiols in the binding site as high affinity binding of [3H]LY181984 was reduced by treatment with the covalent thiol blocking reagent, N-ethylmaleimide (NEM), or by oxidation with dilute hydrogen peroxide but was protected by glutathione or dithiothreitol. Elimination of binding of [3H]LY181984 by NEM was prevented by excess unlabeled LY181984 (an active sulfonylurea) but less so by excess LY181985 (an inactive sulfonylurea). The binding proteins were specifically labeled with thiol reagents following reaction of unprotected thiols with unlabeled thiol reagents. Binding proteins at ca. 34 kDa were labeled. Plasma membrane proteins after solubilization with SDS under strongly reducing conditions still bound sulfonylurea. [3H]LY181984 binding to plasma membrane proteins resolved on SDS-PAGE correlated as well with proteins in the 30-40 kDa range. PMID- 7794963 TI - Riboflavin uptake by rat liver basolateral membrane vesicles. AB - The present study examined riboflavin (RF) uptake by purified rat liver basolateral membrane vesicle (BLMV). Uptake of RF was found to be Na(+)- and pH independent in nature. Studies on RF uptake by BLMV as a function of incubation medium osmolarity have indicated that the uptake is the result of transport (66.5%) into the intravesicular space as well as binding (33.5%) to membrane surfaces. The process of RF uptake by BLMV was saturable as a function of substrate concentration with an apparent Km of 3.55 +/- 0.70 microM and Vmax of 39.89 +/- 3.24 pmol/mg protein/5 s, respectively. cis-Addition of unlabeled RF and its structural analogs lumaflavin and lumichrome inhibited the uptake of [3H]RF while trans-addition of unlabeled RF stimulated the efflux of [3H]RF from preloaded vesicles. No effect on RF uptake was found by the membrane transport inhibitors probenecid, 4,4-diisothiocyanotostilbene-2,2-disulfonic acid (DIDS) and 4-acetamido-4-isothiocyanatostilbene-2,2'-disulfonic acid (SITS). Induction of a transient positive intravesicular space led to a slight stimulation of RF uptake, while induction of a negative intravesicular space led to a slight inhibition in RF uptake. These results demonstrate the existence of a membrane associated carrier system for RF uptake by liver BLMV. This system appears to be Na(+)- and pH-independent and is influenced to a certain degree by changes in transmembrane electrical potential. PMID- 7794964 TI - Parasite-induced permeation of nucleosides in Plasmodium falciparum malaria. AB - A mechanism which mediates the transport of the nonphysiological nucleoside, L adenosine, was demonstrated in Plasmodium falciparum infected erythrocytes and naturally released merozoites. L-Adenosine was not a substrate for influx in freed intraerythrocytic parasites or in normal human erythrocytes nor was L adenosine transported in a variety of cell types including other parasitic protozoa such as Crithidia luciliae, Trichomonas vaginalis, Giardia intestinalis, or the mammalian cells, Buffalo Green Monkey and HeLa cells. L-Adenosine transport in P. falciparum infected cells was nonsaturable, with a rate of 0.13 +/- 0.01 pmol/microliter cell water per s per microM L-adenosine, yet the transport was inhibited by furosemide, phloridzin and piperine with IC50 values between 1-13 microM, distinguishing the transport pathway from simple diffusion. The channel-like permeation was selective as disaccharides were not permeable to parasitised cells. In addition, an unusual metabolic property of parasitic adenosine deaminase was found in that L-adenosine was metabolised to L-inosine by both P. falciparum infected erythrocytes and merozoites, an activity which was inhibited by 50 nM deoxycoformycin. No other cell type examined displayed this enzymic activity. The results further substantiate that nucleoside transport in P. falciparum infected cells was significantly altered compared to uninfected erythrocytes and that L-adenosine transport and metabolism was a biochemical property of Plasmodium infected cells and merozoites and not found in normal erythrocytes nor any of the other cell types investigated. PMID- 7794965 TI - Comparison of phosphatidylcholines containing one or two docosahexaenoic acyl chains on properties of phospholipid monolayers and bilayers. AB - Docosahexaenoic acid (DHA) is the longest and most unsaturated of the n - 3 fatty acids found in membranes. Although a number of membrane properties have been demonstrated to be affected by the presence of this fatty acid, its mode of action has yet to be clearly elucidated. Prior reports on biological membranes have not distinguished the effect of mono-docosahexaenoyl phospholipids from those caused by phospholipids containing docosahexaenoic acid in both chains. This report compares properties of monolayers and bilayers composed of either 1 stearoyl-2-linolenoyl-sn-glycero-3-phosphocholine (as a control), 1-stearoyl-2 docosahexaenoyl-sn-glycero-3-phosphocholine or 1,2-di-docosahexaenoyl-sn-glycero 3-phosphocholine. When compared to the mono-DHA phosphatidylcholine (PC), the di DHA PC occupies a much larger area/molecule, supports a more fluid and permeable bilayer, and is less susceptible to peroxidation. Monolayers made from either phospholipid are not condensable by cholesterol. We suggest many of the membrane properties linked to the presence of DHA may be the result of phospholipids which have lost their normal positional selectivity and have incorporated DHA into both positions. PMID- 7794966 TI - EPR study of annexin V-cardiolipin Ca-mediated interaction in phospholipid vesicles and isolated mitochondria. AB - The properties of the binding of annexin V to variously composed phospholipid vesicles have been studied by applying a recently developed EPR method, using an annexin V spin label. By this approach, this protein is seen to bind to acidic phospholipid-containing vesicles, as reported, thus confirming the reliability of the method. In addition, binding of this annexin to cardiolipin-containing vesicles has been studied in more depth, and the protein has been shown to have a distinct affinity for this phospholipid. As a cardiolipin-rich natural membrane system, mitochondrial membranes and mitoplasts from rat liver were considered, and a strong binding of AV to these membranes was observed. Having compared this binding with that to phospholipid vesicles, cardiolipin-rich microdomains in the mitochondrial membranes are proposed as the putative mitochondrial binding sites for annexin V. PMID- 7794967 TI - Effect of sphingosine and stearylamine on the interaction of phosphatidylserine with calcium. A study using DSC, FT-IR and 45Ca(2+)-binding. AB - The lamellar gel to lamellar liquid-crystalline phase transition of dipalmitoylphosphatidylserine (DPPS) multilamellar membranes is abolished by the presence of Ca2+ at DPPS/Ca2+ molar ratios of 2:1 or lower. However, when equimolar sphingosine (SPH) or stearylamine (SA), which are positively charged at the pH studied in this work, were included in DPPS vesicles, the phase transition of DPPS was still observed by differential scanning calorimetry, even in the presence of very high Ca2+ concentrations such as a DPPS/Ca2+ molar ratio of 1:10. According to that, delta H was similar for samples formed by equimolar DPPS and SPH and SA, either in the presence or in the absence of Ca2+, whereas no phase transition was observed for the pure phospholipid in the presence of Ca2+ at molar ratios lower than DPPS/Ca2+ 2:1. 45Ca(2+)-binding experiments showed that for DPPS/SPH or DPPS/SA molar ratios of 2:1, only half of the Ca2+ was bound to DPPS with respect to pure DPPS, i.e., in the absence of SPH or SA. At concentrations of SPH or SA equimolar with DPPS, the Ca2+ binding was nearly abolished. The effect of SPH and SA on the the apparent pKapp of the carboxyl group of DPPS was also studied in the presence and in the absence of Ca2+ by using Fourier transform infrared spectroscopy. The dehydration of the phosphate group of DPPS induced by the binding of Ca2+ was followed through the observation of the PO2- antisymmetric stretching, and the percentage of dehydrated PO2- groups quantitatively assayed. It was again confirmed that, in the presence of equimolar concentrations of SPH or SA, Ca2+, at concentrations which are saturating for pure DPPS, was not bound at all to DPPS. It was also found that the pKapp was considerably shifted to lower values in the presence of the amino bases, decreasing from 4.6 in pure DPPS to 2.1 and 2.2 for the equimolar mixtures of DPPS with SPH and SA, respectively. These results show that SPH and SA, being positively charged molecules anchored in the membrane, are able of preventing the binding of positively charged ions such as Ca2+ through an electrostatic charge neutralization. PMID- 7794968 TI - Analysis of effects of corticotropin, forskolin and fluoride on activity of adenylate cyclase of bovine adrenal cortex. AB - A mathematical model relating the activity of adenylate cyclase (AC) with concentrations of stimulators, equilibrium dissociation constants, specific activity and efficacies of AC depending on the states of its binding sites has been developed and used for analysis of the data on activation of AC of bovine adrenal cortex plasma membranes presented in (De Foresta et al. (1987) FEBS Lett. 216, 107-112). Equilibrium dissociation constants. chi h and chi l, corresponding to high- and low-affinity forskolin-binding sites were estimated to be 0.37 and 17 microM: these constants characterize forskolin's potency more adequately than does ED50, the concentration eliciting half-asymptotic activity of AC. Corticotropin does not affect the affinity of AC for forskolin whereas fluoride increases this affinity, thus augmenting forskolin's potency. Hormone receptor of adenylate cyclase of bovine adrenal cortex has been suggested to have two or more binding sites for corticotropin. Some unidentified factor(s) may be responsible for the differences found in adenylate cyclase activity in different experiments carried out under similar conditions. The model applied for the analysis may be thought to be the best means for the moment to relate dose-response dependencies with what is known or can be hypothesized about the mechanisms underlying activation of adenylate cyclase. PMID- 7794969 TI - Interaction of bovine heart pyruvate kinase with phospholipids. AB - The interaction between bovine heart pyruvate kinase and liposomes was investigated for various phospholipids as function of pH, and salt concentration using steady-state kinetics and ultracentrifugation. Liposomes made from erythrocyte total lipid fraction and individual phospholipids were used. Pyruvate kinase specific activity increases upon the interaction with the phospholipids. The activation is specifically sensitive to presence of phosphatidylserine in liposomes. L-serine, and phospho-L-serine which are main components of phosphatidylserine head group show also some activation effect. Efficient adsorption of pyruvate kinase to phosphatidylserine liposomes occurs in the pH range 6.0-8.0 and at low ionic strength. Interaction with phosphatidylserine liposomes results in the change of Vmax and Km values for phospho enol pyruvate without marked effect on Km value for ADP, and Hill coefficients for both substrates. The interaction does not seem to influence the cooperativity between binding sites. PMID- 7794970 TI - Alcohol inhibits the activation of NAD-linked dehydrogenases by calcium in brain and heart mitochondria. AB - The effect of ethanol on the Ca(2+)-dependent activation of mitochondrial dehydrogenases in rat brain and heart mitochondria was investigated. ADP stimulated respiration of isolated brain and heart mitochondria (state 3) was stimulated further by submicromolar concentrations of free calcium when respiring on non-saturating concentrations of NAD-linked substrates. The stimulation of oxidative phosphorylation by Ca2+ was correlated with an increase of the mitochondrial matrix free calcium concentration ([Ca2+]m), as measured by fura-2, and with an increased reduction of the mitochondrial NAD(P) pool, indicating an activation of Ca(2+)-dependent dehydrogenases. Sodium inhibited Ca(2+)-dependent stimulation of state 3 respiration and NAD(P) reduction as a result of stimulation of Ca2+ efflux through the Na+/Ca2+ antiporter which reduced the steady-state value of [Ca2+]m. Ethanol stimulated the Na+/Ca2+ antiporter both in brain and heart mitochondria. As a result of this stimulation, ethanol, at pharmacological concentrations (50-300 mM), enhanced the sodium-dependent reduction of [Ca2+]m, and thus attenuated the activation of NAD-linked dehydrogenases and the stimulation of oxidative phosphorylation, by submicromolar concentrations of Ca2+, both in brain and heart mitochondria. This pharmacological effect of ethanol, on brain and heart mitochondria, may be responsible, in part, for the acute and chronic effects of ethanol on brain and heart function and metabolism. PMID- 7794971 TI - Increase in fluidity of human placental syncytiotrophoblastic brush-border membrane with advancement of gestational age: a fluorescence polarization study. AB - The syncytiotrophoblastic brush-border membrane (BBM) of human placenta plays a vital role in the exchange of metabolites between mother and developing fetus. The fluidity of this membrane renders its selective permeable character. To meet the changing needs of the growing fetus with the progress of gestational age changes in the composition and properties of BBM occur. In the present study, decrease in cholesterol/phospholipid ratio of BBM indicated an increase in fluidity with advancement of gestational age. Measurement of the steady state fluorescence anisotropy of labeled liposomes prepared from lipid extract of BBM as well as that of labeled BBM vesicles prepared from native BBM shows decrease in restriction of the bound dye molecule with increased gestational age. Decrease in transition temperature of BBM and enhanced glucose transport through it have been observed with advancement of pregnancy. PMID- 7794972 TI - Target cell membrane sialic acid modulates both binding and fusion activity of influenza virus. AB - Influenza virus binds to cell surface sialic acid receptors, and following endocytosis fuses with the endosome membrane at low pH. Whether sialic acid plays a role in the virus-cell membrane fusion step is not known. We investigated the effect of the removal of cell membrane sialic acid on the fusion activity of influenza virus (A/PR/8/34 strain) toward human T lymphocytic leukemia (CEM) cells at low pH. Fusion was monitored by fluorescence dequenching of octadecylrhodamine incorporated in the virus membrane. Removal of sialic acid by neuraminidase resulted in a drastic reduction in both viral binding and fusion. The association of the virus with neuraminidase-treated cells was enhanced at pH 5, compared to that at neutral pH, probably due to the unfolding of the hemagglutinin and the resulting increase in viral surface hydrophobicity, but the fusion capacity of the virus was reduced significantly. The results were analysed with a mass-action kinetic model which could explain and predict the kinetics of fusion. Our results indicate that binding of influenza virus to sialic acid residues on the cell surface leads to rapid and extensive fusion and partially inhibits the low pH-induced viral inactivation. PMID- 7794973 TI - Electrokinetic charge of the anesthetic-induced bR480 and bR380 spectral forms of bacteriorhodopsin. AB - The translational and rotational electrokinetics of the anesthetic-induced spectral transitions bR568-->bR480-->bR380 of bacteriorhodopsin have been investigated. Formation of the bR480 form is associated with an increase of the purple membrane negative electrokinetic charge, while the transformation of bR480 into bR380 is accompanied by a decrease of the membrane negative charge as compared to that of the 480 nm-absorbing form. Removal of anesthetics leads to the back transitions bR480-->bR568 and (in part) bR380-->bR568; however, the electrokinetic charge of the native membranes is not restored. A strong decrease in the electric polarizability and the appearance of a slow polarizability component are also observed in anesthetic-treated membranes. Comparison with the electrokinetic behaviour of partially delipidated membranes and with that of liposomes composed of purple membrane total lipids suggests that: (i) anesthetic molecules partition mainly at the protein/lipid interface inducing irreversible rearrangement of the boundary lipid layer, and (ii) different mode(s) or site(s) of interaction are responsible for the spectral and surface charge effects. The data are compatible with the hypothesis of anesthetics acting through partial dehydration of the membrane surface. PMID- 7794974 TI - Arthritis hand function test: inter-rater reliability among self-trained raters. AB - OBJECTIVE: The purpose of this project was to examine the inter-rater reliability of the Arthritis Hand Function Test (AHFT), a new instrument for measuring hand strength and dexterity in adults with arthritis. METHODS: Six occupational therapists (two at each of three sites) trained themselves as AHFT administrators using the test manual and training videotape. They recruited 30 adult subjects (10 at each site) with rheumatoid arthritis or osteoarthritis affecting the hands. There were 21 women and 9 men in the sample (mean age, 57.5 years; average time since diagnosis, 14.8 years). Subjects were tested twice, once by each rater from that site. RESULTS: Inter-rater reliability ranged from 0.45 to 0.99 (Pearson r). Because subjects were tested twice, AHFT scores were examined for an order effect. Although scores on all strength items declined by the second test session, and improved for all dexterity items, only the aggregate applied dexterity score showed significant change across all three sites (P = 0.002, 0.001, and 0.031, respectively). CONCLUSIONS: These results suggest the AHFT is a reliable instrument for measuring hand strength and dexterity that requires minimal training on the part of occupational therapist raters. PMID- 7794975 TI - Predictors of hand function in patients with rheumatoid arthritis. AB - OBJECTIVES: The aims of this study were to determine: (1) what factors predict patient self-estimated hand function; (2) what factors predict actual hand function; and (3) the relationship among actual hand function, patient estimates of hand function, and self-assessed activities of daily living (ADL). METHODS: Fifty-two patients with rheumatoid arthritis completed wrist and hand mobility measures, grip strength, pain, stiffness, and estimated hand function tests, along with the Sollerman Grip Function Test (actual hand function), Health Assessment Questionnaire (HAQ), and subscales of the Arthritis Impact Measurement Scales (AIMS). RESULTS: Grip strength and stiffness were the strongest predictors of self-estimated hand function. Flexion and extension deficits in digits II through V were the strongest predictors of actual hand function. Actual hand function and self-estimated hand function were significantly correlated with each other and with the HAQ and AIMS subscales. CONCLUSIONS: Measures of deficit are the most useful in predicting actual hand function, whereas measures of strength and flexibility are most useful for estimated hand function. PMID- 7794976 TI - ARHP: poised for the future. PMID- 7794977 TI - Reliability and validity of the CSSRD functional assessment survey in rheumatoid arthritis. Cooperative Systematic Studies of Rheumatic Diseases. AB - OBJECTIVE: To demonstrate the reliability and validity characteristics of a fast, intensively focused functional assessment questionnaire that has been used in rheumatoid arthritis clinical trials by the Cooperative Systematic Studies of Rheumatic Diseases group (CSSRD). METHODS: Data from three double-blind, controlled clinical trials by CSSRD were used to examine the properties of the Functional Assessment Survey as a measure of physiologic function. RESULTS: The Functional Assessment Survey has reasonable test-retest reliability and convergent validity with the Steinbrocker et al. functional class. It demonstrated appropriate divergent validity with other clinical measures of response, as well as discriminant validity. CONCLUSIONS: The CSSRD Functional Assessment Survey is brief, intensive, and focused. Reliability and validity characteristics have been documented. PMID- 7794978 TI - The sense of coherence scale in patients with rheumatoid arthritis. AB - OBJECTIVE: To analyze Antonovsky's Sense of Coherence (SOC) Scale, in 828 patients with rheumatoid arthritis (RA) from 15 private rheumatology practices. This scale is designed to evaluate strengths within individuals that allow them to select appropriate strategies to deal with stressors; both the total 29-item (SOC-29) total scale and a 13-item (SOC-13) short form of the 29-item scale were analyzed. METHODS: Data were collected through mailed self-report questionnaires as a component of a long-term monitoring program. Internal consistency was evaluated according to Cronbach's alpha. Split-halves reliability was estimated according to the Spearman-Brown prophecy formula. Associations of the SOC-29 and the SOC-13 scale scores with demographic, clinical, and psychological variables were analyzed according to Pearson product moment correlations. RESULTS: Lower SOC-29 and SOC-13 scale scores were correlated significantly with higher scores for difficulty in performing activities of daily living (ADL), a visual analog pain scale score, global health status, and perceived learned helplessness. The levels of correlation for these variables suggest that each measure represents a construct that differs from the SOC. Lower scale scores were also correlated significantly with fewer years of formal education, adjusted for age, sex, and disease duration. CONCLUSIONS: The SOC-29 and SOC-13 scales are reliable and valid in patients with RA. The SOC scale explained in part variation in clinical status in patients with RA. The SOC-13 provides utility comparable to the SOC-29 in patients with RA. PMID- 7794979 TI - Predicting pain among children with juvenile rheumatoid arthritis. AB - OBJECTIVE: Children and adolescents with juvenile rheumatoid arthritis (JRA) often report pain as a major symptom that affects their daily activities. Little is known about the factors that contribute to pain, however. Demographic, disease status, and social-psychologic variables were used to predict pain of JRA. METHODS: Participants were 37 girls and 23 boys who were 7 to 17 years old. Measures included the Hopelessness Scale for Children, the Sadness Scale from the Differential Emotions Scale--IV, and the Social Support Questionnaire--Revised. A pain visual analogue scale served as the criterion measure. RESULTS: Reported pain was modestly correlated with disease duration and age. A hierarchical regression indicated that the predictor variables accounted for a modest amount of variance in pain scores. CONCLUSIONS: The results suggest that the factors contributing to pain in children with JRA are different from those in adults with rheumatoid arthritis (RA). Research is needed to identify the psychologic and socioenvironmental variables that influence pain among children with JRA. PMID- 7794981 TI - Self-efficacy, pain, and physical activity among fibromyalgia subjects. AB - PURPOSE: The purpose of this study was to examine the effects of self-efficacy on self-report pain and physical activities among subjects with fibromyalgia (FM). In addition, descriptive statistics of the Arthritis Impact Measurement Scale (AIMS), a measure developed for use with arthritis patients, were reported. METHODS: Seventy-nine subjects with FM, as classified by the American College of Rheumatology (ACR) criteria, completed the Visual Analogue Scale for Pain, the AIMS, and the Arthritis Self-Efficacy Scale. A myalgic score was obtained during a tender point evaluation. Hierarchical multiple regression analyses were used to assess the effect of self-efficacy on self-report pain and physical activities measures after controlling for demographic variables (age, education, and symptom duration), disease severity (myalgic scores), and psychological distress (negative affect from the AIMS). RESULTS: Higher self-efficacy was associated with less pain and less impairment on the physical activities measure after controlling for demographic and disease severity measures. CONCLUSIONS: This study underscores the unique importance of self-efficacy in understanding pain and physical activities impairment. PMID- 7794980 TI - Dissatisfaction, disability, and rheumatoid arthritis. AB - OBJECTIVES: To investigate dissatisfaction with function in patients with rheumatoid arthritis (RA), and to see if dissatisfaction can be adequately explained by level of function. METHODS: Fifty patients with RA were assessed for disease activity, psychological status, disability, expectation of future disability, and satisfaction with both global function and individual activities of daily living (ADL). RESULTS: Fifty percent of patients expressed dissatisfaction with global function, which correlated more strongly with pain (r = 0.474) and psychological status than with function (r = 0.398). Only 10% predicted improvement in global function. Seventy-two percent expressed dissatisfaction with performing at least one ADL. CONCLUSIONS: Patient dissatisfaction with both global function and individual ADL function is high and cannot adequately be explained by disability alone. Correlation with pain and psychological status implies that modifying these variables (perhaps through education programs about pain relief or relaxation) could reduce dissatisfaction. PMID- 7794982 TI - Iontophoresis: an overview of the mechanisms and clinical application. PMID- 7794983 TI - Evaluation of a community arthritis program in Australia: dissemination of a developed program. AB - OBJECTIVE: To evaluate the effectiveness of a community-based arthritis education program conducted in a number of locations throughout the Sydney, Australia, metropolitan area. METHODS: The program, based on earlier work, comprised 6 weekly sessions of 2.5 hours' duration. The study sample included 175 men and women with different types of arthritis, divided into intervention (n = 104) and control (n = 71) groups. Five outcome measures were selected to evaluate effectiveness of the program: pain perception, knowledge level, self-efficacy, disability index, and self-management behavior. RESULTS: The results indicated that the program was effective in increasing knowledge level (F[1,222] = 10.3, P = 0.001 at 6 weeks; F[1,108] = 7.8, P = 0.006 at 6 months), and a statistically significant difference was found in disability satisfaction 6 months after intervention (F[1,98] = 5.9, P = 0.01], but no statistically significant difference was found in pain perception, self-efficacy, and disability index. CONCLUSION: This research supports some of the successful outcomes which follow an arthritis education program: increased knowledge level and increased disability satisfaction. PMID- 7794984 TI - Use of commercially produced elastic wrist orthoses in chronic arthritis: a controlled study. AB - OBJECTIVE: To examine the efficacy of wrist orthoses on pain, motion, and function of the wrist. METHODS: Consecutive patients were randomized to a treatment group using wrist orthoses or to a control group using no wrist orthoses, in a prospective, controlled, 6-month study. RESULTS: Changes in wrist joint variables and general disease activity variables were not statistically different between the orthosis group (n = 36) and the control group (n = 33). Patients in the orthosis group had 25% and 12% improvements in grip strength and pinch grip and 50% reduction in pain while using the wrist orthosis. CONCLUSION: Use of wrist orthoses improves function and reduces pain, but has no effects after 6 months, compared to a control group, on measures of local or general disease activity. PMID- 7794985 TI - Physical activity in children with juvenile rheumatoid arthritis: quantification and evaluation. AB - OBJECTIVE: To measure daily physical activity in patients with juvenile rheumatoid arthritis (JRA) and in healthy controls, and to identify variables that may influence physical activity in JRA patients. METHODS: Twenty-three prepubertal children, ages 5-11 years, with mild to moderate JRA and no prior exposure to systemic glucocorticosteroids, were compared to 23 healthy children of similar age. Physical activity was measured for 3 days (minimum of one weekend day) using 3 standardized methods simultaneously. Total body movement was assessed by the Caltrac accelerometer and the University of Cincinnati Motion Sensor (UCMS). The Caltrac measured movement in the vertical plane; the UCMS measured movement of 10 degrees or more from the horizontal plane. The type and intensity of daily physical activity was measured by the 3-day activity record, which also recorded the number of hours of daily sleep. Participation and duration of involvement in organized sports was ascertained by questionnaire. RESULTS: The mean physical activity was significantly lower in JRA patients than in controls for the activity diary (P = 0.05). However, daily body movement measured by the Caltrac and UCMS were similar for both groups. Differences were seen in the number of hours of sleep per day (P = 0.02) and participation in strenuous activities (P < 0.01). JRA patients had significantly less participation in organized sports (P = 0.01). CONCLUSION: There was less daily physical activity by this group of JRA patients than for healthy age- and sex matched control subjects. PMID- 7794986 TI - Parents of children with rheumatic disease as peer counselors. AB - OBJECTIVE: A parent consultant program was established to promote active family involvement in the health care process and to provide parent-to-parent support, education, and training. METHODS: Parents of children with rheumatic disease were hired by 7 pediatric rheumatology centers to serve as role models and advocates for other parents whose children attended the clinics. In the clinic, the parent consultants provided support, advocacy, and education regarding specific nonmedical issues. At the local level, they assisted parents in obtaining community-based services, such as individual educational plans at school, local physical therapy, or access to recreational resources. RESULTS: Program impact was evaluated by an anonymous, mail-response questionnaire sent to parents who met with a parent consultant during a clinic visit for their child. Surveys were sent within 6 months of the initial parent consultant meeting; 257 questionnaires were mailed, 33% were returned. The majority of respondents (87%) felt their interaction with the parent consultant was helpful. The general support received and the specific information and/or assistance received were found to be equally useful by respondents. The majority of respondents (98%) stated they would recommend that other parents meet with the parent consultant. CONCLUSION: Parents of children with rheumatic disease are effective peer counselors, providing general support and specific assistance to enhance family involvement in care. PMID- 7794987 TI - Awareness of the prevalence and impact of arthritis: the role of health professionals. PMID- 7794988 TI - Predicting health care use among older osteoarthritis patients in an HMO. AB - OBJECTIVE: To determine factors that predict health care use among members of Health Maintenance Organizations (HMOs). Demographic, health, and psychological factors were examined simultaneously. METHODS: Participants were HMO members 60 years of age or older who had osteoarthritis (OA). All participants reported symptoms of OA, with 90% of the diagnoses confirmed by evaluation of physician records. RESULTS: Age, the presence of other medical conditions, quality of well being, and the Health Worries subscale from the Arthritis Impact Measurement Scales accounted for 11.2% of the total variance in health care contacts. A model including prior health care use, age, quality of well-being, physical impairment, and pain accounted for 29.5% of the variance in utilization rates. CONCLUSION: The best single predictor of health care utilization was prior use of the system. Being older, more impaired, and having lower well-being scores were also predictors of health care use. PMID- 7794989 TI - Physician visits by rheumatoid arthritis patients: a prospective analysis. AB - OBJECTIVE: To examine prospectively, using the behavioral model of health service utilization, patient-initiated physician visits, physician-requested visits, and visits for disease flares by 270 patients with rheumatoid arthritis (RA). METHODS: Four waves of telephone interviews were conducted over 2 years. Hierarchical regression analyses were used to assess the relative contributions to variance explained by blocks of variables indicating need for care and predisposing and enabling factors. RESULTS: Predisposing and enabling factors accounted for 50-67% of the explained variance in the 3 types of visits, while need accounted only for 33-50%. CONCLUSIONS: Studies seeking to identify factors other than need for care that facilitate or inhibit physician visits among RA patients are essential to analyzing the costs of care. PMID- 7794990 TI - Relative contributions of spousal support and illness appraisals to depressed mood in arthritis patients. AB - OBJECTIVE: To examine the ability of cognitive appraisals of illness and spousal support to modify depressed mood in arthritis patients. METHODS: Psychosocial data were collected from 64 married patients with rheumatoid arthritis (RA) within 2 years of diagnosis and at an 18-month followup. RESULTS: The interaction of challenge appraisals with positive support received from the spouse was related to changes in depression over time. There was an increase in depression as challenge appraisals increased when accompanied by greater receipt of positive support, whereas individuals who did not experience a sense of challenge in response to the diagnosis of RA had the lowest levels of residualized depression when they also received higher positive support from their spouses at the beginning of the study. CONCLUSION: The results are considered in terms of the cognitive-behavioral mediation model suggested by Kerns and associates concerning the relationship of chronic pain to depression and have implications for interventions aimed at arthritis patients and their spouses. PMID- 7794991 TI - Health-related quality of life in patients with osteoarthritis in a family practice setting. AB - OBJECTIVE: To study the impact of osteoarthritis (OA) on all areas of a patient's health-related quality of life. METHODS: The Sickness Impact Profile (SIP) was administered to a group of patients with OA selected from a family medicine setting. The results were compared to a reference population, stratified by age, and adjusted for sex. RESULTS: OA was associated with significant impairment, and had an important impact on, health-related quality of life in the areas of ambulation, body care and movement, emotional behavior, sleep and rest, home management, and work, especially in patients ages 41-60. The older patients differed less from the controls than did the younger ones. Items that contributed to the differences between OA patients and controls were mainly related to physical limitations. CONCLUSION: Most dysfunctions related to OA are physical. PMID- 7794992 TI - Concordant and discrepant views of patients' physical functioning. AB - OBJECTIVE: Although considerable research has been done on patient-physician interaction, few studies have examined discrepancies between patients and physicians in their assessments of the patient's physical functioning. One recent study reports such discrepancies between rheumatologists and 41% of their rheumatoid arthritis patients. This article reports data replicating that study and examining the relationships between such discrepancies and a number of other variables. METHODS: This is a longitudinal study of 158 patients with rheumatoid arthritis who were interviewed 4 times over a 2-year period and who reported their levels of physical functioning on the Arthritis Impact Measurement Scales. At the time of the fourth interview, the rheumatologists rated each patient's physical functioning on the revised criteria published by the American College of Rheumatology. RESULTS: Rheumatologists' assessments of their patients' physical functioning were discrepant with the patient's assessment for 35% of these patients. Twenty-seven patients were rated as worse than they rated themselves and 28 were rated as better. There were no differences between the concordant and the two discrepant groups in demographic or health status characteristics. PMID- 7794993 TI - [Profit sharing: a psychiatric management strategy]. AB - This paper outlines the development and implementation of profit sharing, an innovative technique to motivate and empower chronically mentally ill members of a psychiatric rehabilitation program. In some ways, this intervention resembles a token economy. Members are paid script for program participation, which they then exchange for rewards. In contrast to token economies, however, the profit sharing system is financed, administered and monitored by program members. This method has the advantage of enhancing program participation and involvement by allowing members to keep the rewards earned through their own efforts. Data collected over a five-year period suggest that profit sharing increases program utilization, average daily attendance and the number of positive vocational outcomes. PMID- 7794994 TI - [The "Soft Approach": a program of rehabilitation of chronically mentally ill elderly patients]. AB - The authors report on "The Soft Approach", a program for chronic mentally ill elderly patients, which they have implemented in a gero-psychiatric unit in New York City. Using a professional team, their approach treats the medical problems, and the various degrees of dementia encountered, in a positive and coordinated effort centered around daily recreational and socializing activities; these include off-ward events and outings away from the hospital. The goals of the program are increased independence and eventual community living. The importance of their medication regime is stressed with patients throughout the program. PMID- 7794995 TI - [Introduction of an evaluation strategy in the psychosocial rehabilitation of psychiatrically handicapped adults in Belgium: an approach matching programs to the needs of beneficiaries]. AB - This article examines the implementation of an evaluation strategy in a socio professional rehabilitation centre. In this project, measuring instruments were developed with the double intention of providing a clinical evaluation that would be useful for the intervener, as well as ensuring an evaluation of the clientele's evolution that would assist in the observation of effects resulting from interventions within groups of beneficiaries. Following the first analysis of data, which showed that the program had difficulty in retaining its clientele, a second study was undertaken to establish the profile of beneficiaries on whom the program had a positive impact and those for whom the stay at the centre did not provide any significant effects. PMID- 7794996 TI - [Social reintegration: a dynamic program to help psychiatric patients acquire functional and interpersonal skills]. AB - Since new mental health policies have been developed, government and community based organizations appear to be working closer toward facilitating the social reintegration process regarding persons experiencing psychiatric problems. This article describes a project which fosters the development of a patient's functional and interpersonal skills in a para-hospital environment: supervised apartments. The program's objective is to encourage awareness of an individual's situation and especially to allow him or her to acquire and experiment a certain number of skills for the ultimate purpose of reintegrating the community. This project is carried out by the psychiatry department of Notre-Dame Hospital in collaboration with the Maison l'Echelon Inc., a non-profit organization that manages a group of supervised apartments for psychiatric patients. PMID- 7794997 TI - [Single-parent mothers, poverty and mental health: review of the literature]. AB - The goal of this article is to discuss an overview of literature published from 1968 to 1993 and dealing with links between single-parenting, poverty and mental health. A total of 56 articles were selected based on the most current data banks. Results show that the population of single-parent mothers is growing and that they are becoming increasingly poor. Of the six mental health variables listed by the author, four (psychological distress, self-esteem, perception of one's own skills and psychological isolation) clearly demonstrate that single parent mothers are in a less healthy mental state than are mothers in two-parent families. Results also indicate that self-esteem, distress and psychological well being are affected by economic variables. Results therefore vary according to the variable being measured. Although single-parent mothers experience more psychological discomfort than mothers in two-parent families, they do not seem to experience more serious mental health problems. The authors argue that future research on the subject should take into consideration a certain number of aspects, discussed in the conclusion of this article, which account for links between single-parenting, poverty and mental health. PMID- 7794998 TI - [From deinstitutionalization to social rejection: the point of view of ex psychiatric patients]. AB - A series of in-depth interviews conducted with ex-psychiatric patients who use alternative resources in the area of mental health has revealed several manifestations of rejection, stigmatization and discrimination. These are experienced as significant and determining with respect to the social integration of patients, as well as harmful to their quality of life in the community. Data shows that this population suffers from social isolation due to lack of communication with community members and from various forms of rejection and disparating attitudes on the part of entourage. Their fragile socio-economic conditions confine them to live in a sub-culture and at the fringe of society. PMID- 7794999 TI - [Rehabilitation and psychotherapy of chronic psychoses. Study of a cognitive approach in French speaking countries]. PMID- 7795000 TI - [An evaluation of multi-faceted program: intervention with violent spouses]. AB - This article presents the results obtained from a study on the efficiency of a treatment program aimed at violent spouses. More particularly, three dimensions are evaluated, namely the program's effect on the incidence of violent behaviour (physical, verbal, psychological and sexual), on the participant's attitude toward the roles of men and women, as well as on the self-esteem of participants. Data on the violent behaviour of men was collected from them and from their spouses. The study reveals that the program tends to reduce all forms of violence and that its maximum efficiency is mostly noticed in the period following the program. On a different note, the program is less efficient when basing results on women's declarations than on men's. Finally, the program's efficiency varies according to the form of violence observed. PMID- 7795001 TI - [The biomedical approach and perspectives of medical sociological contributions to psychosocial rehabilitation]. PMID- 7795004 TI - [The integrated approach to social reintegration: beyond "case management" and psychosocial rehabilitation]. AB - Recently in western countries mental health systems are, slowly but systematically, adopting case management (CM) as a system of service delivery. Nonetheless, case management remains undefined, poorly described and its characteristics uncharted and unresearched. Social reintegration is a comprehensive model that incorporates strategies of service delivery aimed at solving the problems encountered by CM in the maintenance, enhancement of clients quality of life and social functioning and, social and community acceptance are addressed and issues of costs and collaboration between institutions is explored in depth. PMID- 7795003 TI - [The power of professionals in rehabilitation: the example of service users' group in social care]. AB - Increasingly the purposes and focus of mental health rehabilitation has turned away from a concern to maximise the functioning of individuals towards an interest in helping people with mental needs to interact sufficiently well with their environment so as to gain independence in everyday life (Wing, 1980). Rehabilitation is to be seen, therefore, as a process rather than an event (Sheppard, 1984). In other words, rehabilitation not simply a single treatment (or fixed series of treatment) but often will be a longer term intervention to maintain social functioning and support adaptation. A failure to understand this distinction or to translate it into guiding principle which informs all aspects of professional practice in psychiatric rehabilitation results in misdirected effort (or, worse, in a series of empty rituals which reinforce dependence) (Watts and Bennett, 1993; Brandon, 1991). A central question for all the caring professions engaged in psychiatric rehabilitation, therefore, is how to utilize their skills to enable and support this process. PMID- 7795002 TI - [Instrumentalism and psychosocial rehabilitation. Development of methodological processes related to the "intermediate spaces"]. AB - In psychosocial rehabilitation, institutional actors which are not focused on the "intermediate space" (term coined by the authors to describe the time-space of interpersonal, solution-oriented communication filled by the actor and the patient) are faced with an identity crisis and other problems, some of which are linked to a instrumental vision of their practice. Such a vision leads to a discursive and theoretical approach, yet interferes with potential partnerships. Also, it traps open and solution-oriented relational situations by favouring that which is focused on acts of a prescriptive and normative nature. This state of affairs is encouraged by several factors linked to the actor's status, to health policies and to the evaluation of such policies. In future, effective work in this "intermediate space" will require that actors use other inductive models on which to base their practice which, incidentally, remains at the fringe of social care and support. PMID- 7795005 TI - [Assertive "case management": a complete evaluation of a hospital based program]. AB - This study measured the effectiveness of a comprehensive community treatment program modeled after an Assertive Case Management structure. It used an experimental random assignment design. Over a six month period, patients in the ACM program, despite their acute symptoms, had better vocational and social outcomes, less symptomatology, lower recidivism and length of hospital stay rates. Most revealing was their reported quality of life and lower perceived family burden than the hospital program patients. Further, the ACM patients' overall treatment costs were lower than the patients in the hospital program. PMID- 7795006 TI - [Researchers: at the interstices of institutional and community levels]. PMID- 7795007 TI - [Working with families in the long-term treatment of schizophrenic disorders]. AB - The authors present and discuss, within a systems frame of reference, the main aspects of family interventions with adults affected by long-term schizophrenic disorders involved in psychosocial rehabilitation. Special attention is paid to mutual influence between the interventions aimed at individual disability and those centered on family attitudes, beliefs and interactional patterns. PMID- 7795008 TI - [Suicide in patients with borderline personality disorder]. AB - Patients with borderline personality disorder present a clinical challenge, largely because of their chronic suicidality. Long-term outcome research shows that about 10 per cent of borderline patients will eventually complete suicide, but that is difficult to predict which patients are at highest risk. There is no evidence at present that treatment prevents suicide. Clinical recommendations are made, suggesting that suicide prevention should not be the major priority of therapy of these patients. PMID- 7795010 TI - [Research approaches in the meaning of suicide among teenage Inuit]. AB - Is it possible to approach the suicide of teenage Inuit in the same way as in other communities, especially when taking into account the fact that suicide in Inuit is part of their traditions? The issue raised by the author essentially concerns the interpretation of data. This article offers new approaches to researching the meaning of suicide through a cultural viewpoint of the phenomenon and by taking into consideration the socio-political context. The author presents a new vision of suicide as an all-encompassing social fact that opens the door to more relevant interventions. PMID- 7795009 TI - [Suicide in hospitalized patients]. PMID- 7795012 TI - [The family physician and the suicidal patient]. AB - As a background for the discussion, a minor literary survey points out the potentiality for intervention and prevention of suicide and suicide attempts in the primary care setting. The main purpose of this paper is to discuss what options this implicates when it comes to improve the family physicians' ability to recognize and to handle suicidal signals from the patient. A summary of the important papers already published by Rutz and his group in Sweden clearly demonstrates the importance of education concerning depressive disorders and other immediate matters. The significance of communicative skills of the doctor in this clinical situation in undoubted but still mostly unexplored and finally this is shortly discussed. PMID- 7795011 TI - [The effectiveness of suicide prevention centers]. AB - The basic services provided by suicide prevention services as well as research on the evaluation of these services are reviewed whether there is evidence that the services prevent suicide and also how the services might evaluate their internal activities. A plea is made for much greater involvement both by scholars and by counselors in the evaluation of these services, for only by formulating clear goals or hypotheses and examining whether they have been achieved or confirmed can we expect to improve the quality and range of suicide prevention services offered. PMID- 7795013 TI - [Evaluation of long-term effectiveness of a social reintegration program]. AB - This study evaluates the impact of a rehabilitation program developed by a specific unit (304) of Louis H. Lafontaine Hospital to prepare severely disabled long-term psychiatric inpatients for discharge. Patients who participated in the program were evaluated three years after their discharge and compared to control patients paired to them by age, sex and years of hospitalization and discharged from other units of the hospital. The results suggest that the rehabilitation program, if coupled with an adequately staffed residential environment giving patients continuous care, offers a better outcome, at least in the case of the severely disabled long-term psychiatric inpatients. PMID- 7795014 TI - [Attitude of nursing personnel towards patients with AIDS: impact of an awareness program]. AB - The goal of this study was to evaluate the impact of an awareness program aimed at experienced personnel and personnel in training who provide healthcare services to patients with AIDS. The purpose of the program was to prepare healthcare staff psychically in working with patients. Six groups of approximately ten people each watched a video showing a nurse stating her concerns about AIDS. After the video, people were encouraged to express their own emotions regarding the disease and people suffering from it. Other participants making up a control group did not attend the discussion. All subjects (N = 124) completed questionnaires on their attitudes and knowledge about AIDS before and after the discussion. Results show an improvement of attitudes with respect to homosexuality, as well as a better understanding of AIDS. However, these observations do not seem to correspond with a more favourable attitude towards AIDS patients. An analysis of these discussions reveals that there is a conflict between the will to help patients and the feeling of shame when faced with the difficulty of showing empathy. As a result, the authors recommend that training programs aimed at healthcare personnel be geared to alleviate this conflict. PMID- 7795015 TI - [Concrete and illustrative history of disunity in the town of Lille, France]. PMID- 7795016 TI - [Social networks in a sample of adolescents in Quebec: closeness of relations and personal adaptation]. PMID- 7795017 TI - [Suicide among young male adults in Quebec: psychopathology and utilization of medical services]. AB - Seventy five young male adults between the age of 18 and 35 who had committed suicide were compared with 75 male adults still alive matched for age, residence, marital and employment status. For each group a principal respondent was interviewed in order to reconstitute the psychological profile of each individual, as well as their utilisation of health services. This was completed by the study of the coroner's reports and the medical records when available. At six months the prevalence for all axis I diagnosis was 88.8% for the suicide group and 37.3% for the control group. Among the subjects who had committed suicide 38.7% were afflicted by major depression, 24% by alcohol dependency and 28.7% were dependent on drugs. Borderline personalities were present in 28% of the suicide group compared to 5% in the control group. Forty five percent (45%) of the subjects who had killed themselves had consulted a mental health professional in the year preceding the suicide compared to 5% in the control group. However, 78.5% of the suicide group had consulted during the same period a health professional compared to 73.3% of the controls. PMID- 7795018 TI - [Family ecology, social networks and suicidal behavior in the school milieu]. AB - This article sums up the outcome of a research project conducted in Montreal schools in 1987 and 1988, and focusing on how family ecology and social networks relate to strong suicidal tendencies among teenagers. Two groups were involved in the study: one with 78 suicidal persons, the other with 72 non-suicidal persons. Teenagers in each group were interviewed separately. All subjects reported high lack of attention from at least one of the two parents. Results also show that parents of suicidal teens experience permanent break-ups less frequently in comparison to the other group. However, families of suicidal teens tend to experience deeper changes in the structure of the family unit following an initial separation. With respect to moving, there are no significant differences, whether in the number of moves or the important people, have access to as many different kinds of support and report the same number of conflicts. In all these comparisons, however, suicidal teenagers do name a proportionately higher number of adults. This leads the authors to hypothesize that a higher rate of parental separation among non-suicidal teens could represent a protective factor rather than a vulnerability factor, as is usually suggested. In terms of social networks, the fact that suicidal teens seek out adults to a greater degree could impede on their socializing with peers and, therefore, on their social integration. PMID- 7795019 TI - [After suicide: a unique mourning experience?]. AB - Canada's national task force on suicide suggests that people who mourn a suicide make up a group that is itself at risk. Literature shows that mourners of a suicide have a suicide rate that is nine times higher than average. While some authors suggest that this type of mourning is more intense and of a longer duration that for other types of mourning, other authors doubt this hypothesis. But what happens in reality? Is suicide mourning truly different from other types of mourning? Is it really a unique mourning experience? These are some of the questions the authors of this article have attempted to answer. Following an in depth review of studies on the matter, the authors conclude that the mourning of a suicide encompasses certain characteristics that manifest themselves especially in more vulnerable people. PMID- 7795020 TI - [Mental disorders and suicide]. PMID- 7795021 TI - [The impact of suicide on the caregiver]. AB - Suicide ("the killing of one's self") raises one crucial question: what does the manifest desire of death bring out in oneself and in others? For those providing care and support who are confronted with the voluntary death of a client or patient, the question is particularly difficult to address. Using the story of a suicide in an institution, the authors reveal the nature of defense mechanisms at play within the group of caregivers. Whether it be a traumatic daze, denial, guilt or depression, these individual and collective reactions to the event hinder the mourning process and threaten cohesion within the institution. Members of an "institution in crisis" must try to relieve their tensions by refraining from withdrawal, banalities, being haunted by suicide and implementing pseudo solutions. The purpose of such an exercise is especially to avoid the cancellation or displacement of necessary thought process about the origins, implications and consequences of a suicide taking place within an institution. The authors discuss the founding principles and guidelines for group exploration of these phenomena. Without this coming-to-terms with the crisis, the authors point out that the institution could find itself in a rut where discussion focuses only on when and where things went wrong, and how it turned its back on a suffering patient. PMID- 7795022 TI - Violence in America: an integrated approach to understanding and prevention. AB - Violence in our country has reached epidemic proportions, especially among our youth. Of 22 industrialized nations, the United States has the highest homicide rate among young males 15 to 24 years of age. To reduce the incidence of violence, we must radically shift our approach to emphasize prevention and intervention. There are several ways of achieving violence reduction through these means. The scientific approach requires the determination of causation and risk factors to shed light on the patterns of violence and the effects on subgroups of the population. Also required is the development of targeted programs aimed at specific high-risk populations. In the area of youth violence intervention, programs must focus on young children and their parents, often children themselves, to prompt appropriate changes in knowledge, skills, and attitudes. Community-based programs can go a step further to initiate changes in the social environment that will create opportunities for adequate housing, job training or employment, or academic achievement. These efforts exemplify the notion that violence is not a factor of race, but rather is based on socioeconomic factors, particularly poverty and racism. PMID- 7795023 TI - Substance abuse and violence: cause and consequence. AB - Substance abuse has been associated with violent behavior for many decades. While the relationship is the same today as it was in the past, the pervasiveness of the association, and the consequences, are more dramatic. There are two ways in which substance abuse is related to violence. First, violence can be and is perpetrated under the influence of substances, and second, violence related to substance abuse stems from the trade in drugs, which is all too often focused in poor and underserved communities. The elimination of the market for drugs, and thus the reduction in the demand for drugs, will bring about a reduction in substance abuse-related violence. PMID- 7795024 TI - Proceedings of the 7th National Conference on Health Care for the Poor and Underserved. Preventing Violence and Abusive Behavior: A Public Health Agenda. Nashville, Tennessee, October 3, 1994. PMID- 7795025 TI - The cost of tolerance for violence. AB - Our society evinces a high tolerance for violence. This acceptance of certain forms of violent behavior is ingrained in the American value system, established through our history in the simple struggle to survive. Beginning with the colonial era, through the settlement of the western frontier, and during the wave of immigrant arrivals, Americans often used violence to establish basic rights. Sociobiological explanations of individual violent tendencies focus on genetic predisposition established through natural selection--or survival of the fittest- while psychoanalytical perspectives define extreme violence as a deviant form of natural aggression. On the other hand, criminologists define all violence as deviant. In today's society, physical force is considered to be justifiable when expressing political dissent and protecting self and property, and less so during domestic disputes. PMID- 7795026 TI - Domestic violence: Nashville's increased response. AB - Nashville is more actively responding to the problem of domestic violence with increased efforts on the part of both the courts and police. Two court dockets are now devoted solely to domestic dispute cases, with a team of special prosecutors assigned to such cases. In another recent move, the Nashville Police Department formed a team of 25 police officers trained to specifically deal with domestic confrontations. These efforts, together with the growing number of support groups for victims and treatment programs for batterers, indicate Nashville's commitment to breaking the cycle of domestic violence. PMID- 7795027 TI - Moving away from an emergency room mentality: an unorthodox view of the judicial role in violence prevention. AB - Discussions about the role of the judicial system in dealing with violence focus on cases of violent crime. While the criminal courts are an important component of any overall violence reduction strategy, the response is largely reactive rather than preventive. Family law cases, on the other hand, provide opportunities for the provision of prevention and early intervention services to families at risk. Such services are critical to successfully address the epidemic of violence. PMID- 7795028 TI - Research and policy directions in violence: a developmental perspective. AB - Violence and violence-related behaviors have become important research and policy considerations in the 1990s. Both private and public institutions have assembled considerable research associated with male violence directed against children, youth, women, and other males. Data currently available indicate that focusing on males as perpetrators is an appropriate direction for violence research. In this paper, suggestions are offered regarding a developmental-socialization hypothesis for further research in the area of male violence. PMID- 7795029 TI - Witnessing violence: making the invisible visible. AB - In his novel of Black life circa the 1950s, Invisible Man, Ralph Ellison laid bare the wasteful, destructive societal consequences of racism. At the close of the 20th century, we are faced with the phenomenon of another social problem, likewise unresolved and likely to haunt us similarly: urban violence. Following Ellison's example, this paper seeks to explore the impact of violence's stark invisibility by discussing a research strategy that better explains the terrifying phenomenon of violence. In order to comprehend the totality of violence, macro- and micro-level variables have to be introduced into the research design and measured over time. Therefore, research might best address violence if it was designed to include variables of poverty and racism, and was more inclusive of research from a broader range of scientific disciplines. PMID- 7795030 TI - Prior nonfatal firearm injuries in detainees of a large urban jail. AB - Detainees of large urban jails have may health risks including injuries related to violence and firearms. A survey of 582 randomly selected detainees entering the Cook County Department of Corrections during the summer of 1994 found that 51 percent had previously entered hospitals for violence-related injuries, and 26 percent survived prior gunshot wounds. Patterns of firearm injuries were different from patterns of violence affecting the general population. Factors common to those with prior firearm injuries included witnessing a shooting at an early age, tattoos, previous sexually transmitted diseases, easy access to a semiautomatic weapon, and prior incarceration. Implications and prevention strategies are discussed. PMID- 7795031 TI - The National Drug Control Strategy: the first-line approach to decreasing violence in our communities. AB - The National Drug Control Strategy is designed to address all aspects of drug abuse: drug use, drug trafficking, and drug-related crimes. The nine-pronged program encompasses efforts at the federal, state, and local levels, forming a partnership between government and the private and public sectors. The strategy includes prevention initiatives that reduce the demand for drugs; individualized treatment programs for high-risk groups; greater community policing efforts to reduce violent crimes by drug users and pushers; and education aimed at children and adults. It is a national strategy that strives to find solutions at the local level. PMID- 7795032 TI - Clinical violence intervention: lessons from battered women. AB - Attempts to address violence intervention and prevention in clinical practice are hampered by the difficulty of creating definitions and categories that accurately reflect community experience. Current medical and legal paradigms, for instance, do not integrate gendered experience into definitional understanding of domestic violence and, consequently, risk the development of systems of care that poorly address women's needs. A model of women's experience of domestic violence and key elements of clinical intervention are presented. Health and public health agencies need to actively integrate an understanding of gender relations in violence intervention and prevention. PMID- 7795033 TI - Gang violence. AB - During childhood and adolescence, the formation of groups or gangs is a normal part of the growing process. Playmates, school friends, Boy and Girl Scout troops are each examples of the natural inclination to form group attachments that provide a stable social outlet. However, gangs, as we now know them, are part of the pathological process brought on by the inability to disassociate from adolescent groupings, and more frightening, the result of infiltration by criminal elements, such as drug dealers, who exert violent influence on impressionable youngsters, particularly in major urban areas. The transition of gangs from innocent to deadly is due in large part to society's failure to respond to the environment that causes their pathology. In order to reverse the process, society must engage in programs that reinforce the gang or group experience as a positive one by incorporating adult supervision and mentoring as essential elements. PMID- 7795034 TI - Violence in schools: why--and what can we do about it? AB - This paper discusses the causes and effects of the violence that occurs in schools. The author explores the notion of need (to be a part of, to belong, and to be connected) as it relates to the tendency toward violence, and conversely, the association between success in school, which allows for the development of positive self-esteem and therein socially acceptable behavior, with a tendency toward nonviolence. The paper explains how behavioral factors common to poor and disadvantaged students, such as a lack of esteem for self and for their educational institution contributes to a failure cycle. The paper also suggests that the development of the affective domain, coupled with sensitivity to culture, good instruction, and an educational environment that nurtures success, leads to an effectively functioning individual with a social, economic, political, and ethnic identity. PMID- 7795035 TI - Clinical assessment of gang violence risk through history and physical exam. AB - Primary-care clinicians can assess gang involvement and gang violence risk during the routine history and physical exam. This paper forwards a model for history and risk assessment. The objective of creating the model was to develop a practical prototype for clinicians to use in this assessment. The history and physical exam variables were determined by a study of the etiology and correlates of gang membership and gang violence. The history and physical risk assessment tool is based on standard patient care algorithms. It works best in a managed care setting with a high incentive for violence prevention and cost reduction, and where access to a broad range of traditional and nontraditional referral sources exists. Representative referrals are discussed. PMID- 7795037 TI - Building community capacity to prevent violence through coalitions and partnerships. AB - This paper will explore the most effective strategic roles that coalitions can play in the prevention of complex, entrenched social and health problems such as violence, alcoholism, and other substance abuse problems. There is a growing body of "wisdom" and research literature that suggests that the most effective role for community coalitions and partnerships in terms of prevention is to build the capacity of community leaders and their institutions to better serve their constituencies. This can be accomplished through the use of the coalition to strengthen the enabling or support system for community initiatives. An enabling system provides a variety of services, including training and consultation, information and referral, networking and local coalition development, communication, incentive grants and recognition, information and social marketing, resource development, and research and evaluation services. This paper also outlines the key internal capacities a coalition will need in order to establish this system. PMID- 7795038 TI - Street Soldiers: violence prevention over the airwaves, a phenomenon. AB - Problems common to inner-city youths such as truancy, drug use, teen pregnancy, and the possession of weapons often consign them to a bleak future, one bereft of opportunities. Violence, therefore, becomes a means of survival. To break the cycle of violence among inner-city youth, it is essential to overcome the negative behaviors that give rise to this violence. The Omega Boys Club of San Francisco is founded on the notion of the extended family, and provides the active support and emotional guidance once found in the home and immediate community. Through a three-tiered program of change, the club has developed a plan to help stop the violence. This has been extended beyond the Bay Area via a radio call-in show called Street Soldiers, in which discussions focus on violence in the home and on the streets. PMID- 7795036 TI - Physical rehabilitation and violence: initiatives of the National Institute on Disability and Rehabilitation Research. AB - The paper presents an analysis of violence-related data from the National Spinal Cord Injury Database within the context of violence-related projects of the U.S. Department of Education's Office of Special Education and Rehabilitative Services. The National Spinal Cord Injury Database is managed by the Spain Rehabilitation Center at the University of Alabama at Birmingham, which is one of 13 Model Spinal Cord Injury Care System centers funded under a grant from the U.S. Department of Education's Institute on Disability and Rehabilitation Research. There are 1,732 cases of spinal cord injury (SCI) due to violence enrolled in the database. This enrollment provides a longitudinal sample, an analysis of which shows that African American individuals and persons of Hispanic origin represent an increasing percentage of new cases, and that an increasing percentage of individuals within these populations is incurring SCI as a result of violence. PMID- 7795039 TI - A comprehensive approach to violence prevention. AB - Violence by and against youth has reached horrifying proportions. Debate continues about the causes of youth violence and appropriate solutions. This paper discusses a comprehensive holistic approach to violence prevention, as exemplified by the program at The Door--A Center of Alternatives in New York City, an organization that services at-risk youth aged 12 to 21. With a multinodal approach, The Door deals with the identified root causes of violence, such as the alienation and lack of empowerment experienced by many of today's youth, and provides lifeskills training and concrete services related to the consequences of poverty, unemployment, low levels of achievement, and hopelessness. PMID- 7795040 TI - An overview of Tennessee state legislation affecting violence prevention. AB - Homicide is the number one cause of death among African American youth, both male and female. Largely to blame for Black-on-Black violence is the sense of alienation our youth feel from society. To counter this phenomenon of violence it is essential to empower youth. Through education and community-based programs we can draw them away from the materialistic to the realistic. By banding together as mentors to our youth we can provide them with a sense of history and heritage, and thereby equip them with the self-identity originating from self-respect. PMID- 7795042 TI - Addressing domestic violence in the African American community. AB - This paper focuses on the problem of spouse abuse in the African American community and discusses intervention programs designed to reduce domestic violence. The problem of domestic violence is not new. However, there is increased concern about it, such that the criminal justice system has changed its policy toward this act. This policy considers domestic violence a crime, and arrest the most efficient way to prevent it. Further, providing counseling programs to men is one of the efforts some criminal justice departments are now using. The two programs discussed in this paper are programs used by the criminal justice system. They are designed to prevent repeated domestic violence by focusing on the education of conflict resolution to deal with anger, denial, and jealousy, and the development of interpersonal skills that assist in channeling anger and poor interpersonal communication into positive modes of conduct. Some characteristics of batterers are noted. PMID- 7795041 TI - "I have a future" comprehensive adolescent health promotion: cultural considerations in program implementation and design. AB - "I Have a Future" Adolescent Health Promotion Program is a life options program. The program uses the Nguzo Saba (seven principles) and African philosophy to systematically address violence and attitudes reinforcing the use of violence. The Nguzo Saba promotes self-respect, and commitment to and support for developing a positive community. Data was collected from four public housing developments--two served as match control sites. Adolescents residing in neighborhoods in which the program operated had greater acceptance of the Nguzo Saba than those in matched communities. Those who perceived themselves as having life options engaged in fewer delinquent/violent acts. There was a strong negative correlation between the acceptance of the Nguzo Saba and the number of reported delinquent/violent behaviors. There was a positive relationship between the acceptance of the Nguzo Saba and positive self-concept, psychosocial maturity, and clarity of goals. PMID- 7795043 TI - The epidemic of youth violence in America: using public health prevention strategies to prevent violence. AB - Violence is exacting an increasingly heavy toll on individuals across the country, causing a marked rise in fear and frustration. However, historical attempts to address violence have been both episodic and inconsistent. There has not been a comprehensive and coordinated, prevention-oriented approach. Many law enforcement experts now agree that violence must be met with solutions from disciplines other than law enforcement, those of public health included. These experts acknowledge that social conditions such as family stability, education, and other societal institutions directly affect the behavior of juveniles and thereby the safety of communities. No single strategy, institution, or discipline can create the changes needed to reduce violence in America. Preventing violence demands not only a long-term commitment but a comprehensive set of strategies and new partnerships. These combined efforts must focus on prevention and not solely on aggressive responses to violence. PMID- 7795045 TI - Vasculitides associated with infections, immunization, and antimicrobial drugs. AB - Many pathogenic microbes can induce a complex series of immunologic, endothelial cell, and hemorheological activation cascades and dysfunctions and can cause interactions of various components of the vessel wall with formed and noncellular elements of the blood. These interactions can result in manifold vasculitides. This article reviews the pathogenetic, clinicopathologic, and therapeutic aspects of infection-related vasculitides; it includes a brief discussion of parasitic, drug-related, and immunization-associated vasculitides as well as of the infection-related features of vasculitides of the central nervous system, retinal vasculitides, ecthyma gangrenosum, and erythema nodosum. Viruses are mainly associated with small-vessel vasculitides, whereas bacterial infections affect vessels of all sizes, including the aorta. The vasculitides associated with fungal infection usually are characterized by erythema nodosum and involve large vessels. The search for microbes as causes of or contributors to vasculitides should continue. Infectious vasculitides may become increasingly important as the number of immunocompromised patients grows. PMID- 7795044 TI - Bacterial vaccine vectors and bacillus Calmette-Guerin. AB - Recent advances in biotechnology now allow a more modern approach to the development of vaccines, particularly that of recombinant vaccines. Bacterial vaccine vectors have the advantage over viral vectors in that the former have the ability to express a greater number of antigens in different forms. Although no recombinant bacterial vaccines are currently in use, bacillus Calmette-Guerin (BCG), Salmonella species, and Escherichia coli are being developed as vaccine vectors. We review plasmid systems and mutant strains developed for the expression of foreign antigens, with particular emphasis on those developed for BCG. We describe the development of antigen expression systems as well as the immune response elicited by recombinant BCG vaccine strains to bacterial and human immunodeficiency virus (HIV) antigens. A modified recombinant BCG carrier with selection for the stable maintenance of rDNA is proposed. PMID- 7795046 TI - Sclerosing osteomyelitis and Actinomyces naeslundii infection of surrounding tissues. AB - We present the case of a young man with chronic Actinomyces naeslundii infection in the lower leg who underwent a below-the-knee amputation after unsuccessful attempts at diagnosing and eradicating the infection. Actinomycetic organisms from environmental sources can engender a dense fibrotic tissue response without fistulae. Such a response led to a painful, sclerosing, nonsuppurative infection of the bone and surrounding tissues in our patient. This clinical picture, at least the bony and periosteal reaction, was compatible with Garre's osteomyelitis. PMID- 7795047 TI - Cytomegalovirus ureteritis as a cause of renal failure in a child infected with the human immunodeficiency virus. AB - Cytomegalovirus (CMV) infection is common in patients infected with human immunodeficiency virus. Hemorrhagic cystitis and tubulointerstitial nephritis have been recognized as complications of CMV infection, and these complications lead to hematuria and compromised renal function. We describe a case of CMV infection of the ureters in a child with vertically acquired human immunodeficiency virus infection; the child presented with severe suprapubic pain, and prolonged macroscopic hematuria and intermittent acute renal failure developed subsequently. PMID- 7795048 TI - Bartonella (Rochalimaea) species as a cause of apparent "culture-negative" endocarditis. AB - Bartonella quintana (formerly Rochalimaea quintana) is a recently recognized cause of apparent "culture-negative" endocarditis. We describe a 39-year-old, homeless man who developed aortic valve endocarditis caused by B. quintana. He had a history of alcoholism and was seronegative for the human immunodeficiency virus. We established that B. quintana was the cause of the endocarditis on the basis of the isolation of B. quintana from blood cultures, the compatibility of histochemical stains of cardiac valve tissue, the reactivity of the polymerase chain reaction specific for B. quintana on cardiac valve tissue, and the failure to isolate an alternative causative organism despite extensive efforts. This is the second report of endocarditis caused by B. quintana and the fourth report of endocarditis caused by a Bartonella species. On the basis of the findings of this report and those of other recent reports, further study is warranted to determine the overall role of Bartonella species in apparent culture-negative endocarditis. PMID- 7795049 TI - High-level resistance to aminoglycosides: comparison of community and nosocomial fecal isolates of enterococci. AB - Fecal carriage of enterococci highly resistant to streptomycin, gentamicin, and kanamycin was examined in 64 healthy volunteers with no exposure to hospitals and in 53 hospitalized individuals. High-level resistance to streptomycin and gentamicin was found in fecal specimens from 3% and 0, respectively, of the healthy volunteers and in fecal specimens from 41% and 15%, respectively, of the hospitalized individuals. We found that high-level resistance to kanamycin was also more common among hospitalized individuals than among healthy volunteers (36% vs. 17%). The frequent occurrence of high-level resistance to kanamycin in fecal isolates confirms that amikacin is a poor choice when attempting to achieve synergistic therapy for enterococcal infections, in particular for those infections that are nosocomially acquired. PMID- 7795051 TI - Pasteurella multocida tonsillitis: case report and review. AB - Pasteurella multocida is frequently part of the normal flora of the nasopharynx and digestive tract of several wild and domestic animals. Although P. multocida can produce a variety of upper and lower respiratory tract infections, only four previous cases of tonsillitis caused by this organism have been reported. We present a case of pasteurella tonsillitis in a 30-year-old female who was exposed through her cat, which manifested upper respiratory symptoms. PMID- 7795052 TI - Varicella gangrenosa with toxic shock-like syndrome due to group A streptococcus infection in an adult: case report. AB - Varicella gangrenosa is a rare and serious complication of chickenpox that has been described in children only. We describe a case of an adult with varicella gangrenosa that presented as necrotizing fasciitis of a limb. This infection is caused by group A streptococcal superinfection of the skin lesions due to chickenpox. It can be misdiagnosed, with fatal consequences. Because of prompt recognition and aggressive surgical and medical treatment, the patient survived without loss of the affected limb. PMID- 7795053 TI - Trichoderma pseudokoningii as a cause of fatal infection in a bone marrow transplant recipient. PMID- 7795050 TI - Malignant external otitis due to Aspergillus flavus with fulminant dissemination to the lungs. AB - Malignant external otitis secondary to aspergillus infection is rare, and only 10 cases have been reported in the literature. Nine of 10 patients responded to therapy and survived their infection. There have been no previous reports of dissemination of Aspergillus species from the ear to other organs. We describe a case of malignant external otitis due to Aspergillus flavus that disseminated hematogenously to the lungs. The result was an overwhelming, miliary pulmonary infection, which progressed very rapidly to respiratory failure and death. Pathological examination of lung tissue revealed multiple microabscesses and hyphal elements that had invaded the lung parenchyma from small pulmonary arteries. PMID- 7795054 TI - Fatal intravascular hemolysis in a patient with Clostridium perfringens septicemia. PMID- 7795055 TI - Fatal clostridial sepsis in a previously healthy woman. PMID- 7795056 TI - Long-term resolution of disseminated Mycobacterium avium complex infection in a patient with AIDS. PMID- 7795057 TI - Candida parapsilosis prosthetic joint infection unresponsive to treatment with fluconazole. PMID- 7795058 TI - Active human herpesvirus 6 infection in an adolescent male. PMID- 7795059 TI - Teicoplanin selects for Staphylococcus aureus that is resistant to vancomycin. PMID- 7795061 TI - Group C streptococcal bacteremia in patients infected with the human immunodeficiency virus. PMID- 7795060 TI - Clarithromycin-induced hepatotoxicity. PMID- 7795062 TI - Breakthrough cerebral toxoplasmosis in patients with AIDS who are being treated with clarithromycin. PMID- 7795063 TI - Primary coinfection with human immunodeficiency virus and cytomegalovirus presenting as acute rhabdomyolysis. PMID- 7795065 TI - Prosthetic hip-joint infection due to Listeria monocytogenes. PMID- 7795064 TI - Interaction between azoles and amphotericin B in the treatment of candidiasis. PMID- 7795066 TI - Meningitis due to lymphocytic choriomeningitis virus: four cases in France. PMID- 7795067 TI - Current therapeutic approaches to viral hepatitis. PMID- 7795068 TI - Cytomegalovirus infections of the nervous system in patients with AIDS. AB - Retinitis due to cytomegalovirus (CMV) infection is a widely recognized complication of advanced disease due to human immunodeficiency virus type 1 (HIV 1). Less appreciated are other neurological manifestations of CMV infection in persons with AIDS. Dr. J. Allen McCutchan has comprehensively reviewed the various clinical presentations of CMV neurological disease as well as the methods of diagnosis, the neuropharmacology of available antiviral agents, the results of therapy, and the potential for prevention of these sequela of advanced immunosuppression. As the ability to prevent diseases such as Pneumocystis carinii pneumonia, bacteremia secondary to Mycobacterium avium, tuberculosis, serious fungal infections, and toxoplasma cerebritis is increasing, physicians must now treat more HIV-1-infected persons with CMV disease. This AIDS Commentary provides a timely update of the current state of our knowledge regarding this serious problem. PMID- 7795071 TI - Effect of splenectomy on T lymphocyte subsets in patients infected with the human immunodeficiency virus. AB - A case-control study was conducted at two institutions to determine whether the absolute CD4 lymphocyte count or the percentage of lymphocytes bearing the CD4 marker (i.e., the CD4 percentage) is a more accurate indicator of underlying immune status in splenectomized patients infected with human immunodeficiency virus (HIV). Each of nine splenectomized HIV-infected cases was matched with six nonsplenectomized HIV-infected controls--three matched for CD4 lymphocyte count and three for CD4 percentage. In analyses including the eight cases with an initial CD4 lymphocyte count of > 200/mm3, controlling for the CD4 count revealed differences between cases and controls in terms of CD4 percentage (range, 10%-41% and 17%-54%, respectively; P < .01) and Centers for Disease Control and Prevention (CDC) clinical stage (P = .06). Controlling for the CD4 percentage revealed a significant difference between cases and controls in terms of CD4 count (range, 396-1,040 and 55-784 cells/mm3, respectively; P < .01) but not CDC clinical stage (P > .7). These data suggest that the numerical relationship between the CD4 lymphocyte count and the CD4 percentage among splenectomized HIV infected patients with more than 200 CD4 cells/mm3 differs from that among nonsplenectomized patients. The CD4 percentage appears to be a more accurate indicator of the underlying level of immune function in the former group of patients. PMID- 7795069 TI - Pretreatment regimens for adverse events related to infusion of amphotericin B. AB - Infusion-related adverse events (IRAEs) such as nausea, vomiting, fever, chills, and thrombophlebitis that are associated with amphotericin B therapy often lead clinicians to prescribe a number of adjunctive pretreatment medications in an attempt to reduce the incidence and severity of these events. The purpose of this study was to determine the incidence of IRAEs during the first week of systemic amphotericin B therapy and to identify pretreatment regimens that are effective in preventing these IRAEs. Three hundred ninety-seven adult inpatients receiving amphotericin B therapy were prospectively monitored, and data regarding IRAEs and pretreatment regimens were collected. Of these patients, 282 (71%) developed at least one IRAE during the first 7 days of therapy. The IRAEs most commonly reported were fever (51% of patients) and chills (28%), followed by nausea (18%), headache (9%), and thrombophlebitis (5%). The most common regimens included diphenhydramine, a corticosteroid, acetaminophen, and heparin, administered alone or in combination with these or other drugs. Overall, common pretreatment regimens were similar in efficacy to no pretreatment in the prevention of IRAEs. Thus empirical premedication for IRAEs associated with amphotericin B cannot be routinely advocated; instead, patients should be treated when symptoms first arise and then premedicated for subsequent amphotericin B infusions. PMID- 7795070 TI - Leptotrichia buccalis bacteremia in patients treated in a single bone marrow transplant unit. AB - We describe four cases of bacteremia due to Leptotrichia buccalis (an organism that is part of the normal human oral flora) that occurred in a bone marrow transplant unit over a 3-month period. All of the patients were neutropenic, all had mucositis or esophagitis, and all were receiving antimicrobial prophylaxis with ciprofloxacin and vancomycin (drugs to which Leptotrichia is resistant). One patient died of adult respiratory distress syndrome; the others had minimal symptoms. Pulsed field gel electrophoresis of bacterial DNA digested with Sma 1 demonstrated a unique banding pattern for each isolate, indicating that the isolates belonged to distinct strains. Quantitative gas-liquid chromatography of whole-cell free fatty acids confirmed the uniqueness of the strains, obviating the need to search for a common source of infection. We postulate that this outbreak resulted from antibiotic selection pressure on the oral flora in patients who had been compromised by severe neutropenia and mucosal disruption. PMID- 7795072 TI - Growth-deficient mycobacteria in patients with AIDS: diagnosis by analysis of DNA amplified from blood or tissue. AB - Amplification and sequencing of mycobacterial ribosomal RNA genes (16S rDNA) may permit the detection of growth-deficient species (i.e., those exhibiting no growth or those whose growth is delayed for more than 12 weeks). Of blood samples from 26 patients with AIDS and a liver sample from one additional AIDS patient, three samples (two of blood and the one of liver) were positive by polymerase chain reaction only; cultures of these three samples remained negative for more than 12 weeks. Analysis of amplified 16S rDNA from blood revealed a sequence characteristic of Mycobacterium genavense in the first case, in which one of many previous blood cultures had also been positive for M. genavense. The sequences found in the second and third cases were characteristic of Mycobacterium avium. The sample from the second patient was a liver biopsy specimen in which acid-fast bacilli were visualized; the culture of this specimen yielded M. avium after 7 months. The third sample was a blood sample from a patient in whom a relapse of treated M. avium infection was suspected. These results indicate that amplification and sequencing of mycobacterial 16S rDNA may permit early diagnosis and provide a rationale for treatment of infections due to growth-deficient mycobacteria. PMID- 7795073 TI - Relapse of Mycobacterium leprae infection with ocular manifestations. AB - A case of ocular leprosy as the manifestation of persistent or relapsed Mycobacterium leprae infection approximately 20 years following treatment is reported. The clinical and pathological features of this case are described, and the molecular methods needed to arrive at the definitive diagnosis are examined. If blindness is to be averted, clinicians must have a high index of suspicion for the diagnosis of ocular leprosy when anterior segment changes are noted during ophthalmologic examination of a patient from an area in which M. leprae is endemic. The indolent nature of ocular leprosy may require lifelong surveillance and therapy to insure sight preservation. PMID- 7795075 TI - Nosocomial acquisition of multiresistant Acinetobacter baumannii: risk factors and prognosis. AB - To identify risk factors for and prognostic indicators of the nosocomial acquisition of multiresistant Acinetobacter baumannii in an intensive care unit, we prospectively studied 40 patients: 13 who were infected with this organism and 27 who were colonized. Isolates were identified by pulsed-field gel electrophoresis; the infected/colonized patients were compared with 348 noninfected, noncolonized patients by logistic regression analysis and with matched historical controls in a cohort study. The severity of illness (evaluated by the APACHE II score; P < .05) and previous infection (P < .001) were retained as independent risk factors for acquiring A. baumannii. Logistic regression analysis selected a high APACHE II score (P < .01) and the acquisition of A. baumannii (P < .01) as factors independently associated with death. The acquisition of A. baumannii was associated not only with high mortality but also with a length of stay on the intensive care unit in excess of that due to the underlying disease alone; specifically, the attributable mortality was 25%, with a risk ratio for death of 2.0 (95% confidence interval, 1.11-3.62), and the duration of stay for infected/colonized patients was 10.3 days longer than that for controls (P < .001). PMID- 7795076 TI - Fatal sepsis due to a beta-lactamase-producing strain of Fusobacterium nucleatum subspecies polymorphum. AB - A patient with Waldenstrom's macroglobulinemia was treated empirically with imipenem for sepsis related to oropharyngeal infection and responded within 24 hours. When blood cultures yielded Streptococcus agalactiae, the regimen was changed to ampicillin and gentamicin. The patient's condition rapidly deteriorated, and she died 3 days later. After her death, a strain of Fusobacterium nucleatum subspecies polymorphum producing beta-lactamase (PEN-Y; group 2a) was isolated from blood cultures. A literature review revealed increasingly frequent isolation of beta-lactamase-producing strains of F. nucleatum. Thus strains of F. nucleatum isolated from blood and other specimens from patients with serious infections should be tested for beta-lactamase production. PMID- 7795074 TI - Studies on the serodiagnosis of toxoplasmic lymphadenitis. AB - The purpose of this study was to determine the value of conventional and newer serological tests (toxoplasmic serological profile) in the diagnosis of toxoplasmic lymphadenitis (TL). We studied 40 consecutive patients with biopsy proven TL. Cervical, axillary, or occipital adenopathy was present in 72.5%, 20%, and 7.5% of the patients, respectively. Low-grade fever, fatigue, general malaise, or sore throat were present in only 6 (15%) of the 40 patients. A positive result for all serological tests was time dependent from the clinical onset of lymphadenopathy. The initial serum samples were positive for antibody for each patient, as shown by a Sabin-Feldman dye test. Between 3 and 6 months after clinical onset of TL, all of the patients had antibody titers of > or = 1:1,024. The ELISA was positive for IgM antibodies in all of the patients in the first 3 months. Detection of IgA or IgE antibodies or an acute pattern in the differential agglutination test was helpful in diagnosing TL in those patients who had negative, low-positive, or equivocal titers of IgM antibodies (as measured by ELISA) after 3 months. A toxoplasmic serological profile on the first serum specimen drawn after clinical onset of TL had a sensitivity of 100%. It is advisable to obtain such a serological profile in cases of asymptomatic lymphadenopathy before biopsy is carried out, especially for those individuals who have negative or equivocal IgM antibody titers. PMID- 7795077 TI - Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features. AB - To determine the prevalence of fungal liver infection at autopsy in marrow transplant recipients, we reviewed autopsy results for the period 1980-1989. Cases were compared to randomly chosen autopsied controls without fungal infection. Fungal liver infection was found in 67 (9%) of 731 patients. Fungal cultures of liver lesions were positive for 34 of 67 patients, most of whom had been culture-positive for the same fungal species (largely Candida) during life. Multivariate analysis revealed that independent predictors of fungal liver infection were deep fungal infection after transplantation (RR, 35), colonization or superficial infection after transplantation (RR, 13), and severe liver dysfunction caused by veno-occlusive disease of the liver and/or graft-versus host disease (RR, 7). Clinical and laboratory findings during the last month of life revealed no differences between cases and controls. Liver imaging studies performed during the last 15 days of life had a sensitivity of only 18% for detecting fungal liver lesions. PMID- 7795078 TI - Cutaneous Mycobacterium kansasii infection: case report and review. AB - A case of cutaneous Mycobacterium kansasii infection is reported, and 28 similar cases are reviewed. Cutaneous infection may resemble sporotrichosis and is often associated with systemic illness, immunosuppression, skin pathology, or contact with contaminated water. Immunosuppressed patients with M. kansasii infection may present with atypical clinical features (such as cellulitis and seroma) and atypical histology (absence of granulomas), which may delay diagnosis and effective treatment. The incidence of disseminated M. kansasii infection, which has a worse prognosis, is higher among immunosuppressed patients. When M. kansasii infection is confined to the skin, the disease is usually indolent. Chemotherapy with a variety of agents, including traditional antituberculous agents as well as erythromycin, minocycline, and doxycycline, has been successful, although in vitro resistance to isoniazid and p-aminosalicylic acid is common. Reducing the dose of corticosteroids may be a beneficial adjunct to therapy for M. kansasii infection. PMID- 7795079 TI - Postexposure rabies vaccination during pregnancy: effect on 202 women and their infants. AB - This prospective study of 202 pregnant Thai women who received postexposure treatment for rabies with a tissue culture-derived rabies vaccine and human or equine rabies immune globulin revealed an adverse reaction rate similar to that seen among nonpregnant Thai patients who received the same treatment. Tissue culture-derived rabies vaccines as well as immune globulins are safe to use for postexposure prophylaxis during pregnancy. Such treatment should never be withheld or delayed if the patient possibly was exposed to rabies. PMID- 7795080 TI - Ehrlichiosis--a cause of prolonged fever. AB - Human ehrlichiosis is a recently described illness that is thought to be tick borne. Most recognized cases of human ehrlichiosis manifest as an acute nonspecific febrile illness. The natural history of untreated symptomatic disease is largely unknown. Over a 4-year period, we identified 41 cases of human ehrlichiosis by serological testing, polymerase chain reaction analysis, or both methods. The principal finding for six of the patients was protracted fever. The duration of their fevers ranged from 17 to 51 days. At the time of presentation, all six patients had clinical features, laboratory features, or both consistent with a diagnosis of ehrlichiosis. Polymerase chain reaction analysis helped to rapidly confirm the diagnosis for four of five patients tested. The diagnosis of human ehrlichiosis should be considered for patients with prolonged fever who live in an area of endemicity. PMID- 7795082 TI - Epidemiological investigation of infections due to Alcaligenes species in children and patients with cystic fibrosis: use of repetitive-element-sequence polymerase chain reaction. AB - Twenty-one isolates of Alcaligenes species were recovered from the respiratory tract of 16 patients at Texas Children's Hospital over a 1-year period. All but one were identified as Alcaligenes xylosoxidans; the remaining isolate was identified as Alcaligenes faecalis (formerly Alcaligenes odorans). Thirteen of 21 isolates were from the sputum of eight patients with cystic fibrosis (CF), two of whom were persistently colonized. The remaining isolates were recovered from intubated children. Patterns produced by repetitive-element-sequence polymerase chain reaction (rep-PCR), with use of either repetitive extragenic palindromic (REP) or enterobacterial repetitive intergenic consensus (ERIC) primers, showed that strains from different patients were distinct. This observation ruled out a common-source outbreak. Strains repeatedly cultured from the two persistently colonized patients over several months had identical rep-PCR patterns. We conclude that, similar to Pseudomonas aeruginosa, Alcaligenes species (most often A. xylosoxidans) colonize the respiratory tract of intubated children and of patients with CF. Colonization of patients with CF was associated with an exacerbation of pulmonary symptoms. PMID- 7795081 TI - High incidence of resistance to multiple antimicrobials in clinical isolates of Streptococcus pneumoniae from a university hospital in Korea. AB - One hundred thirty-one strains of Streptococcus pneumoniae isolated from clinical specimens between January 1991 and April 1993 were serotyped and tested for susceptibility to 10 antimicrobials by the agar dilution method. Five serotypes (6A, 6B, 14, 19F, and 23F) accounted for 67% of all isolates. Seventy percent of isolates were not susceptible to penicillin, exhibiting either intermediate resistance (37%) or high-level resistance (33%); 82% of isolates from children and 59% of those from normally sterile body fluids were resistant to penicillin. A significantly increased rate of penicillin resistance (P < .01, Fisher's exact or chi 2 test) was associated with hospitalization, an age of < or = 15 years, ongoing antimicrobial therapy at the time of isolation of the organism, nosocomial acquisition, and several specific serotypes (6, 14, 19F, and 23F). No penicillin-resistant strain showed beta-lactamase activity. Various proportions of the penicillin-resistant strains also displayed resistance to cefaclor (89%), cefotaxime (82%), chloramphenicol (65%), erythromycin (52%), and ciprofloxacin (15%), but none was resistant to teicoplanin or vancomycin. The prevalence of pneumococcal resistance documented in Korea in this study is among the highest figures published to date. PMID- 7795083 TI - Herpes simplex virus type 2 meningitis in the absence of genital lesions: improved recognition with use of the polymerase chain reaction. AB - Herpes simplex virus type 2 (HSV-2) is known to cause aseptic meningitis, which can be recurrent. The diagnosis of HSV-2 infection is suggested when meningitis occurs simultaneously with genital lesions but may be obscure if genital lesions are not present or are not appreciated. Viral culture of the CSF is sometimes positive, but it may also be negative, especially in cases of recurrent disease. We report three cases of HSV meningitis in young women who did not have a history of genital herpetic lesions and for whom genital lesions were not noted on presentation. With use of the polymerase chain reaction (PCR), HSV DNA was detected in CSF from all three patients. The diagnosis of HSV meningitis was further confirmed by a positive culture of CSF in one patient's case and by demonstration of intrathecal synthesis of HSV antibodies in a second patient's case. The use of PCR can improve the recognition of HSV meningitis in adults presenting with aseptic meningitis, even in the absence of herpetic lesions. PMID- 7795084 TI - Rapid oral desensitization to trimethoprim-sulfamethoxazole (TMP-SMZ): use in prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS who were previously intolerant to TMP-SMZ. AB - Trimethoprim-sulfamethoxazole (TMP-SMZ) is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS. However, adverse reactions ascribed to TMP-SMZ are common in such patients. We previously described a rapid method of oral TMP-SMZ desensitization in patients with AIDS and varying degrees of intolerance to the drug. To assess the feasibility, safety, and long-term clinical utility of our desensitization protocol, we retrospectively studied 22 consecutive patients who underwent desensitization. Prior to the procedure each of the study subjects had exhibited moderate to severe reactions to TMP-SMZ. Desensitization was successfully completed in 19 (86%) of the patients. The three patients for whom desensitization failed experienced chills and/or vomiting that resolved promptly with symptomatic therapy. One of the 19 patients was unavailable for long-term follow-up. Of the remaining 18 patients, three discontinued taking TMP-SMZ within 2 weeks of desensitization because of macular rash and fever. The other 15 (71%) of the evaluable patients tolerated both desensitization and subsequent prophylaxis and took TMP-SMZ for a mean of 14 months (in some cases, for as long as 41 months). None had P. carinii pneumonia while receiving TMP-SMZ. These results indicate that most patients who are presumed to be TMP-SMZ-intolerant can be rapidly desensitized with oral TMP-SMZ and subsequently receive the drug for protracted periods as effective prophylaxis for P. carinii pneumonia. PMID- 7795085 TI - Etiology of acute respiratory tract infections among children in a combined community and hospital study in Rio de Janeiro. AB - We reviewed data collected between January 1987 and December 1989 on the etiology of acute respiratory infections (ARI) among 827 children in two low-income communities and a hospital in Rio de Janeiro. Respiratory syncytial virus was identified in 38% of cases of ARI, influenza A virus in 1%, parainfluenza 3 virus in 1%, and multiple viruses in 1%. Respiratory syncytial virus was most prevalent among hospitalized children, with seasonal increases in the late fall and winter. The principal bacterial pathogens were Staphylococcus aureus, gram-negative bacteria, Streptococcus pneumoniae, and alpha-hemolytic streptococci. Specimens that were most often positive were pleural fluid (46%) and specimens from other normally sterile sites (24%); normally sterile sites included the CSF, trachea, and lungs. Urine counterimmunoelectrophoresis for S. pneumoniae and Haemophilus influenzae polysaccharide antigens was positive in 3% and 2% of cases, respectively. Pharyngeal cultures yielded low numbers of S. pneumoniae and H. influenzae organisms and higher numbers of gram-negative bacteria. This study demonstrates the high incidence of ARI (4.5 cases per 100 child-weeks) among children in Rio de Janeiro and the high morbidity associated with the illness (ARI is responsible for 25%-50% of all pediatric hospitalizations) and the fact that continued attention must be paid to both viral and bacterial agents of ARI. PMID- 7795086 TI - A randomized, double-blind, placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit. AB - A randomized, double-blind, placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit (ICU) to determine the impact on nosocomial pneumonia, other infections, and emergence of colonization or infection with antibiotic-resistant bacteria. Over 8 months, 30 patients received an oral paste and solution containing polymyxin, gentamicin, and nystatin; 31 patients received a placebo paste and solution. At study entry, patients in both groups were seriously ill (mean acute physiologic score, 27.2), frequently had pulmonary infiltrates (73.8%), and were likely to be receiving systemic antibiotics (86.9%). There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection (50% vs. 55%), nosocomial pneumonia (27% vs. 26%), febrile days (2.3 vs. 2.0), duration of antibiotic therapy (14.0 vs. 13.4), or mortality rates (37% vs. 48%). There was no difference in infections caused by antibiotic-resistant gram negative bacilli, although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients. Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients, although the number of patients in our trial was sufficient to detect only a 50% or greater reduction in pneumonia rates. PMID- 7795087 TI - Saliva and serum as diagnostic media for antibody to hepatitis A virus in adults and in individuals who have received an inactivated hepatitis A vaccine. AB - Saliva was evaluated as a diagnostic fluid for screening individuals for evidence of previous hepatitis A virus (HAV) infection and for evidence of seroconversion after vaccination with inactivated hepatitis A vaccine. A new and simple saliva collection method and an assay for detection of HAV antibody were used; the assay used an antibody capture format. There was complete concordance between the results of saliva-based assays and those of serum-based assays, both of which were used for determining previous natural HAV exposure. However, for vaccine recipients, 100% concordance for saliva-based and serum-based assays occurred only at serum titers of > 9,000 mIU/mL, which were determined with use of the modified HAVAB assay. Saliva provides adequate sensitivity and specificity for determining naturally acquired HAV infection, although it is not useful in clinical trials for determining seroconversion after HAV vaccination. PMID- 7795088 TI - Fever of uncertain origin in patients infected with the human immunodeficiency virus. AB - To assess the frequency and etiology of fever of uncertain origin (FUO) in patients infected with the human immunodeficiency virus (HIV) and to evaluate the yield of diagnostic procedures used in their evaluation, we reviewed the clinical charts of all patients admitted to an AIDS unit during a 15-month period. FUO was defined by the endurance of a fever (temperature, > 38.2 degrees C) for at least 4 weeks before admission and the uncertainty of diagnosis after 3 days, despite appropriate investigation. Of 580 patients evaluated, 50 (8.2%) had FUO. Patients with FUO were at advanced stages of HIV infection (median CD4+ cell count, 71/mm3), and a vast majority (84%) had previously diagnosed AIDS. A cause of the fever was identified for 44 patients (88%), and infections accounted for 82% of all cases. Tuberculosis (42%), visceral leishmaniasis (14%), and disseminated Mycobacterium avium complex infection (14%) were the most frequent diagnoses. Examination of lymph node aspirates, bone marrow biopsy, and culture of clinical specimens for mycobacteria were the procedures with the highest diagnostic yield. Among 6 patients with fever of no identified etiology, 4 died while febrile, and fever was self-limited in the other 2 patients. FUO is common among patients with advanced HIV infection. Since a cause, usually infection, can be identified in most patients, long-lasting fever should not be attributed to HIV itself. PMID- 7795090 TI - Tuberculous pancreatic abscess as an initial AIDS-defining disorder in a patient infected with the human immunodeficiency virus: case report and review. AB - Tuberculosis (TB) is the most common opportunistic infection worldwide in human immunodeficiency virus (HIV)-infected patients. Intraabdominal TB includes lymphadenopathy and focal lesions of solid viscera. Symptomatic expression of tuberculous invasion of the pancreas (supplemented by demonstration of a mass on imaging) is rare among HIV-infected patients. We report the case of an HIV infected patient with a tuberculous pancreatic abscess and review nine similar cases. All patients presented with persistent fever and abdominal pain. The diagnosis was made on the basis of detection of pancreatic mass lesions on computed tomographic (CT) scans and the results of cultures and/or acid-fast stains of peripancreatic abscess material and/or other body fluids. Despite an excellent response to antituberculous therapy, three patients died of unrelated causes. In the setting of a febrile illness with abdominal symptoms, tuberculous pancreatic abscess should be considered in the differential diagnosis for HIV infected patients with a CT-identified mass lesion. PMID- 7795089 TI - Isolated peripheral tuberculous lymphadenitis in adults: current clinical and diagnostic issues. AB - Eight cases of isolated peripheral tuberculous lymphadenitis occurred over a 16 month period at our institution, prompting a literature review to establish the epidemiology, clinical manifestations, and current approaches to diagnosis and treatment of this disorder. It occurs most commonly in young adult women who either are immigrants from areas where tuberculous is endemic or have histories of travel that are suggestive of exposure to Mycobacterium tuberculosis. The disease is indolent and usually presents as a unilateral painless neck mass. Constitutional symptoms are rare, except in individuals infected with the human immunodeficiency virus (HIV). The results of skin testing with purified protein derivative are invariably positive. Excisional biopsy for histopathologic and microbiological evaluations provides the highest diagnostic yield, although fine needle aspiration may be useful for HIV-infected individuals and in areas of the world with a high prevalence of disease. A 6-month course of combination antituberculous therapy is adequate for disease due to susceptible organisms. This infection may be readily diagnosed if suggestive epidemiological and clinical findings lead to expeditious tissue sampling. PMID- 7795092 TI - Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy. AB - We characterized 27 episodes of fungemia in 22 children infected with the human immunodeficiency virus (HIV). Fungemia in these patients presented as a community acquired infection in the setting of outpatient total parenteral nutrition or intravenous antibiotic therapy through a chronically indwelling central venous catheter (CVC). Fungemia developed only in patients with CVCs (P < .001). Non albicans Candida species, Torulopsis glabrata, Rhodotorula rubra, and Bipolaris spicifera constituted 52% of all causes. Fungemia was detected early, within a median of 2.4 days after the onset of new fever, which permitted prompt administration of amphotericin B (mean dosage, 0.7 mg/[kg.day]; median duration, 19 days). CVCs were removed in 23 (85%) of the episodes. We conclude that fungemia in HIV-infected children often presents as a community-acquired infection, is frequently due to newly emerging opportunistic fungi, and can be managed, with a high level of success (95% survival with no posttherapeutic sequelae), by early diagnosis, prompt initiation of amphotericin B therapy, and removal of the CVC. PMID- 7795091 TI - Postoperative toxic shock syndrome. AB - We conducted a retrospective review of all cases of postoperative toxic shock syndrome (PTSS) occurring in two community hospitals from 1981-1993, during which time 390,000 surgical procedures were performed. The incidence was 0.003% (12 cases). All wounds in these 12 cases, from those with scant superficial exudates to those with gross purulence, yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Patients had a mean maximal temperature of 40 degrees C. All patients had a rash, most in a truncal, "sunburn" pattern. Eleven patients had desquamation. Mean time from surgery to onset of symptoms was 4 days. All patients required vigorous fluid resuscitation. No correlation could be demonstrated between the development of toxic shock syndrome and a patient's age, sex, preoperative skin preparation or administration of antibiotics, members of the surgical team, or duration of procedure. All patients with PTSS survived. PTSS should be considered in the differential diagnosis for the acutely febrile, systemically ill postoperative patient, even when surgical wounds are deceptively benign in appearance. Early recognition and treatment of PTSS is essential for successful outcome. PMID- 7795093 TI - Reduced requirement for antibiotic therapy targeting gram-negative organisms in febrile, neutropenic patients with cancer who are receiving antibacterial chemoprophylaxis with oral quinolones. AB - An open, nonrandomized, phase 2 study of 53 adult patients who had 60 neutropenic episodes was conducted to determine if quinolone antibacterial prophylaxis could reduce the need during febrile episodes for parenteral therapy directed at gram negative organisms. Suspected infections among recipients of quinolones were treated empirically with vancomycin and ceftazidime; therapy with the latter was discontinued after 24-48 hours in the absence of infection due to gram-negative organisms. In five neutropenic episodes, patients had no fever or infection. An aerobic gram-negative bacillus was isolated during only 1 (1.8%) of 55 febrile episodes. Febrile episodes occurred at a median of day 15 of cytotoxic therapy. Vancomycin monotherapy was successful in 22 (50%) of 44 evaluable cases. Modification of the vancomycin regimen by the addition of metronidazole or rifampin increased the response rate to 40 (91%) of 44. Response occurred after a median of 4.5 days. Parenteral empirical therapy with amphotericin B was required in only 3 (7%) of 44 cases. The study strategy safely permitted a reduction in the amount and duration of antibiotic therapy directed against gram-negative organisms in febrile neutropenic patients. PMID- 7795094 TI - Bloodstream infection due to Trichosporon beigelii in a burn patient: case report and review of therapy. AB - Trichosporon beigelii is a yeast that has recently been increasingly associated with systemic infections in immunocompromised patients. Few cases have been reported in nonleukopenic patients. We describe what we believe to be the first report of a bloodstream infection due to T. beigelii in a burn patient. Our patient was successfully treated with a combination of amphotericin B and flucytosine. Antifungal susceptibility testing of the T. beigelii isolate showed that the organism was inhibited but not killed by amphotericin B. Burn patients are known to have a transient defect in neutrophil function that can predispose them to some infections. We review the English-language literature of recently reported cases of trichosporonosis and review the various therapies for T. beigelii infection. PMID- 7795095 TI - Short course of ofloxacin for treatment of multidrug-resistant typhoid. AB - In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3 day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever. PMID- 7795096 TI - Failure of treatment for chancroid in Rwanda is not related to human immunodeficiency virus infection: in vitro resistance of Haemophilus ducreyi to trimethoprim-sulfamethoxazole. AB - A comparative open study was performed to evaluate the efficacy of single doses of ciprofloxacin (500 mg) and trimethoprim-sulfamethoxazole (TMP-SMZ; 640 mg/3,200 mg) for the treatment of culture-proven chancroid. Clinical cure or improvement was observed 7 days after treatment in 32 (76.2%) of the 42 patients who received ciprofloxacin and 21 (52.5%) of the 40 patients who received TMP-SMZ (P = .04). Cultures for one (4.5%) of 22 patients not cured with ciprofloxacin and 16 (59.3%) of 27 patients not cured with TMP-SMZ were still positive for Haemophilus ducreyi 7 days after treatment (P < .001). Although 77 (71.3%) of the 108 patients tested were seropositive for HIV-1 antibody, HIV infection and the degree of CD4+ lymphocyte depletion had no effect on clinical and bacteriologic outcome. All isolates of H. ducreyi were highly susceptible to ciprofloxacin (MIC, 0.004-0.06 mg/L). In contrast, resistance to TMP-SMZ (MIC, > or = 4/76 micrograms/mL) was observed in 48.9% of isolates (22 of 45) and was significantly associated with treatment failure. Therefore, the administration of TMP-SMZ, in single or multiple doses, is no longer indicated for the treatment of chancroid in Rwanda. PMID- 7795097 TI - Clinical characteristics, management strategies, and cost implications of a statewide outbreak of enterovirus meningitis. AB - A statewide outbreak of enterovirus meningitis occurred in Rhode Island in the summer of 1991. A comprehensive chart review was conducted for determining the demographic and clinical characteristics of the epidemic and for assessing the interinstitutional variation in treatment strategies. Four hundred eight cases were reported, and enteroviruses were recovered in 61 (68%) of 90 cases in which viral isolation was attempted. Of six isolates that were serotyped, all were echovirus 30. Analysis of cerebrospinal fluid revealed that an increased total white blood cell count and an increased protein concentration were associated with increasing patient age; however, the percentage of polymorphonuclear leukocytes in the cerebrospinal fluid decreased with increasing patient age and longer durations of illness. Marked variations in treatment strategies between institutions were noted in the use of computed tomography of the head, the administration of empirical antimicrobial agents, and the duration of hospitalization. Considerable health resources could have been saved by rapid detection of the virus, dissemination of information about the outbreak, and a conservative approach to clinical management. PMID- 7795098 TI - Abdominal tuberculosis in patients infected with the human immunodeficiency virus. AB - We compared the presentation of abdominal tuberculosis in 43 patients infected with the human immunodeficiency virus (HIV) and in 35 patients without HIV infection. Fever, weight loss, and extraabdominal lymphadenopathy were more common in HIV-infected patients, whereas ascites and jaundice were more frequent in patients without HIV infection. Intraabdominal lymphadenopathy and visceral lesions, visualized on computed tomography scans, were more common in HIV infected patients, whereas ascites and omental thickening were more frequent in patients without HIV infection. Aspirates of abdominal lymph nodes were the only samples revealing acid-fast bacilli in eight HIV-infected patients, yielding a rapid diagnosis. Disseminated tuberculosis was present in 93% of the HIV-infected patients, compared with 31% of those without HIV infection; tuberculosis contributed to death in 23% of HIV-infected patients and in 31% of those without HIV infection. We conclude that abdominal tuberculosis in HIV-infected patients is almost invariably a manifestation of disseminated disease and results in significant mortality. PMID- 7795099 TI - Encephalomyeloradiculopathy of infectious or parainfectious etiology--a new entity? AB - Between 19 March 1990 and 24 December 1992, six persons in Nova Scotia presented with a unique neurological illness. A prodrome of fever and headache was followed by neurogenic bladder, transverse myelitis, and encephalopathy in association with mononuclear pleocytosis of the CSF and nerve-conduction study findings consistent with polyradiculopathy. The spinal cords of three of the patients appeared abnormal on myelograms or magnetic resonance imaging studies. No microbial agent was isolated or demonstrated serologically. All of the patients were treated with antimicrobial agents and corticosteroids. Three recovered completely, but neurogenic bladder persisted in the remaining three. We suggest that this group of patients manifested an encephalomyeloradiculopathy that is likely a new clinical entity of infectious or parainfectious etiology. PMID- 7795100 TI - Mycobacterial lymphadenitis in children: a prospective study of 105 nontuberculous cases with long-term follow-up. AB - Cases of nontuberculous mycobacterial lymphadenitis were analyzed in a prospective study spanning 32 years, from 1958 to 1990. The results are based on personal observations and long-term follow-up. There were 105 cases, all of which occurred in children aged 9 1/2 months to 12 years (median age, 2.92 years). The patients were predominantly female, and the cases occurred more often in the winter and spring. The cervical or facial nodes were involved in 96 cases. An abrupt change in the predominant etiologic agent (from Mycobacterium scrofulaceum to Mycobacterium avium complex) was noted in the 1970s. Positive tuberculin skin tests were the rule, and reactivity was long lasting. Complications included a prolonged initial phase of infection (n = 6) and recurrences 3 1/2 months to 7 years later (n = 5). Resection during the early stage of infection produced the most satisfactory healing. PMID- 7795101 TI - Use of abdominal computed tomography for identifying disseminated fungal infection in pediatric cancer patients. AB - Disseminated fungal infection (DFI) is an important cause of morbidity and mortality among immunosuppressed patients with cancer. To determine the role of abdominal computed tomography (CT) in the diagnosis and management of DFI, we studied the records of patients treated in a pediatric oncology center over an 11 year period. A total of 35 children had CT findings compatible with fungal abscesses in the liver, spleen, and/or kidneys and had fungal infection confirmed by culture, biopsy, or at autopsy. Patients were treated with antifungal agents (median duration of treatment, 57 days) until fever resolved and repeated CT scans demonstrated that the lesions had disappeared, regressed, or stabilized. The 3-month survival rate was 86%. An additional 29 patients with similar characteristics and risk factors had characteristic CT findings, but DFI was not documented with other procedures. These patients were empirically treated for presumed DFI; their courses and outcomes were similar to those for patients with documented DFI. These results suggest that it is reasonable to make a presumptive diagnosis of DFI for patients with characteristic CT findings and clinical features. With appropriate therapy, the prognosis for pediatric patients with cancer and documented or presumed DFI is good. PMID- 7795102 TI - Enteroviral infections of the central nervous system. AB - Infections of the CNS with the nonpolio enteroviruses are common and important causes of morbidity in both children and adults. Studies have recently defined the short-term and long-term outcomes of aseptic meningitis due to the enteroviruses. Focal encephalitis is increasingly recognized as a complication of enterovirus infection. Patients at greatest risk for sequelae of CNS enteroviral disease include neonates and those who are immunocompromised. The clinical presentation may mimic that of bacterial or other viral CNS infections, a circumstance making laboratory diagnosis of paramount importance for reducing unnecessary hospitalization and therapy. Recent advances in PCR technology, including its adaptation to a colorimetric microwell plate format, promise to greatly facilitate diagnosis of enteroviral infections. Promising antiviral drugs for CNS disease and other serious manifestations of enteroviral infections are under development. PMID- 7795103 TI - Geographic latitude and the efficacy of bacillus Calmette-Guerin vaccine. AB - In a meta-analysis of the efficacy of BCG vaccine for preventing tuberculosis, study sites at a greater distance from the equator were associated with a higher efficacy. In a random-effects regression analysis of prospective studies, geographic latitude alone accounted for 41% of the between-study variance. Many factors that vary with latitude may influence the effectiveness of BCG vaccine by modifying the susceptibility of human hosts, the pathogenecity of the organism, or host-agent interactions. These factors include socioeconomic conditions, genetic composition of the population, climate, exposure to sunlight, diet and nutrition, presence of nontuberculous mycobacteria in the environment, completeness of surveillance and follow-up in studies of BCG vaccine, virulence of locally prevalent strains of Mycobacterium tuberculosis, and storage and viability of BCG vaccine. This paper describes the biological plausibility, epidemiologic evidence, and other scientific data bearing on the influence of these factors on the efficacy of BCG vaccine. PMID- 7795105 TI - 1993 Sexually transmitted diseases treatment guidelines. Atlanta, Georgia, 19-21 January 1993. PMID- 7795104 TI - Risks of chronicity following acute hepatitis B virus infection: a review. AB - A bibliographic search was conducted of English-language articles dealing with chronic hepatitis B virus (HBV) infection to evaluate the risk of chronicity following acute infection. Chronic HBV infection was defined as carriage of hepatitis B surface antigen (HBsAg) for at least 6 months. On the basis of incidence studies employing standard serological test methods, the highest risk (80%-90%) of chronic infection was found to be among infected neonates born to hepatitis B e antigen-positive carrier mothers. Of children infected before 6 years of age, chronic infection was reported to develop in approximately 30%. A relatively wide range of risks (< 1%-12%) was found among diverse populations of older children and adults. However, most of the 10 identified incidence studies of generally healthy adults indicated that the risk of chronicity is very low: < or = 5% in eight studies. In addition, the pooled incidence of chronicity was < 5% among two different adult population groups: initially uninfected subjects, who usually experienced asymptomatic infection, and patients presenting with acute hepatitis B. In addition to the primary influence of age, the studies revealed a higher risk of chronic HBV infection among males and among patients with impaired immunity due to various causes. PMID- 7795107 TI - Early intervention for persons infected with human immunodeficiency virus. AB - Early intervention for persons infected with human immunodeficiency virus (HIV) involves characterization of the stage of HIV disease, institution of therapy to prevent associated infections and postpone deterioration of immune function, and assistance in preventing transmission of the virus. This review examines the available data on the efficacy of current recommendations regarding the evaluation and management of persons with early HIV infection. Existing evidence supports the efficacy of physical examination, monitoring of the CD4+ cell count, tuberculin testing (with chemotherapy for persons who test positive), anergy testing, Papanicolaou testing and screening for gonorrhea and chlamydial infection (for high-risk women), screening for syphilis, antiretroviral therapy (for symptomatic patients), and guidance in reducing the transmission of HIV. Recommended measures for which evidence of clinical efficacy is less certain include immunization against infections due to influenza virus, Streptococcus pneumoniae, Haemophilus influenzae, and hepatitis B virus as well as antiretroviral therapy for asymptomatic persons. Quantitative measurement of viral titers appears promising for the monitoring of HIV disease and antiretroviral therapy; the correlations of these titers with clinical end points need to be confirmed. PMID- 7795106 TI - Treatment of syphilis, 1993. AB - Data on treatment of patients with syphilis were reviewed in preparation for revision of the Sexually Transmitted Disease Treatment Guidelines of the Centers for Disease Control and Prevention. Published studies of treatment regimens available and practical for use today were reviewed, particularly in regard to the following issues: treatment for primary, secondary, and latent stages of syphilis; treatment for syphilis during pregnancy; treatment for syphilis in human immunodeficiency virus (HIV)-infected patients; and serological criteria for evaluating response to treatment. The results of treatment and the methodological quality of the studies was considered. Most treatment recommendations must be based on expert judgment and with reliance on the clinical experience over 4 decades. For the treatment of early syphilis in HIV uninfected patients, this is probably sufficient. Data about HIV-infected patients are insufficient both for determining whether current therapy is adequate and for recommendation of an alternative if a change in therapy is deemed necessary. PMID- 7795109 TI - Drugs of choice for the treatment of uncomplicated gonococcal infections. AB - Resistance of Neisseria gonorrhoeae to antimicrobial agents continues to spread and intensify. Choosing an antimicrobial regimen requires knowledge of the comparative efficacy of candidate regimens, as delineated in properly conducted clinical trials; their activity against N. gonorrhoeae in vitro; and their pharmacokinetics and toxicity. We tabulated the results of trials of single-dose antimicrobial therapy for uncomplicated gonococcal infection published after 1980. Thirty regimens comprising 21 antimicrobial drugs have been shown to be highly effective for rectal and urogenital infections; the agents involved are cefixime, cefodizime, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, ciprofloxacin, fleroxacin, norfloxacin, ofloxacin, pefloxacin, temafloxacin, azithromycin, aztreonam, netilmicin, rifampin plus erythromycin stearate, sisomicin, and spectinomycin. Few regimens have been shown to be highly effective against pharyngeal infections. Among those antimicrobial agents available for the treatment of uncomplicated gonococcal infections in the United States, ceftriaxone (125 mg), cefixime (400 mg), ciprofloxacin (500 mg), and ofloxacin (400 mg) appear to offer the best balance of proven efficacy and safety. PMID- 7795108 TI - Recommendations for treatment of chancroid, 1993. AB - Since the 1989 Sexually Transmitted Diseases Treatment Guidelines were published by the Centers for Disease Control and Prevention, changes in the efficacy of the recommended and alternative regimens for the treatment of Haemophilus ducreyi infections have been described. Among recommended agents, erythromycin remains effective, and although a single dose of ceftriaxone appears to remain effective in the United States, limited data from Kenya have shown that this regimen has been associated with treatment failures. Of alternative treatment regimens, trimethoprim-sulfamethoxazole has been associated with widespread failure, but little work has been done to further evaluate the efficacy of the amoxicillin/clavulanic acid and ciprofloxacin regimens. Of the new antimicrobials, azithromycin has been very effective in the United States, but the efficacy of this drug elsewhere has not been thoroughly evaluated. Fleroxacin has been very effective in Kenya. Data from Africa indicate that patients who are infected with the human immunodeficiency virus do not respond to therapy as well as patients who are not, and patients who are uncircumcised may not respond as well to therapy as do patients who are circumcised. PMID- 7795111 TI - Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. AB - We reviewed data on the treatment of bacterial vaginosis published from 1989 through 1992 (articles published after the 1989 publication of the Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines). This review suggests that oral metronidazole (500 mg twice daily for 7 days) is the preferred treatment for bacterial vaginosis. Other effective (but alternative) treatment regimens include single-dose metronidazole (2 g orally), 2% clindamycin vaginal cream (once daily for 7 days), 0.75% metronidazole vaginal gel (twice daily for 5 days), and oral clindamycin (300 mg twice daily for 7 days). Data do not support the practice of routine treatment of male sex partners of infected females. Treatment of bacterial vaginosis during pregnancy should focus on the elimination of symptoms; data on adverse pregnancy outcomes for women with bacterial vaginosis remain insufficient to recommend treatment of asymptomatic patients. Before performing surgical abortion, treatment of bacterial vaginosis (symptomatic or asymptomatic) should be considered to prevent pelvic inflammatory disease. PMID- 7795110 TI - New treatments for Chlamydia trachomatis genital infection. AB - To provide information for the formulation of treatment guidelines, we review recently published articles and abstracts on advances in the treatment of Chlamydia trachomatis genital infection. We ask specific questions about new treatments that are answered on the basis of the results of clinical trials and efficacy studies. New, potentially effective treatments for C. trachomatis genital infection include azithromycin and ofloxacin. Clinical studies indicate that the efficacy of these agents is equivalent to that of the current recommended agent doxycycline. Both azithromycin and ofloxacin are substantially more expensive than doxycycline. Azithromycin has the advantage of being given as a single dose, while doxycycline and ofloxacin are administered for 1 week. Issues of compliance, cost, and toxicity for specific patients should be considered when deciding whether to treat C. trachomatis genital infections with these agents. PMID- 7795112 TI - Treatment options for vulvovaginal candidiasis, 1993. AB - Vulvovaginal candidiasis (VVC), the second most common form of vaginitis, particularly affects women of childbearing age. Since the 1970s, several new agents have become available for the treatment of VVC. This review focuses on options for the treatment of this condition, critically evaluating the relevant published studies. For the treatment of acute episodes of VVC in nonpregnant women, several topical and oral antifungal agents are clinically and mycologically effective. Topical agents should be considered the first line of therapy; however, oral agents are sometimes associated with better compliance among patients. For acute episodes in pregnant women, a topical agent is the treatment of choice. Until data become available on the treatment of VVC in women infected with human immunodeficiency virus (HIV), the same approach as that used for women without HIV infection should be considered as previously written. For recurrent VVC, the optimal maintenance therapy has not yet been established; however, administration of low-dose oral ketoconazole (100 mg/d) has proven effective. Well-designed studies of the best therapy for VVC in women with HIV infection and for recurrent VVC are urgently needed. PMID- 7795113 TI - Cervical cancer screening of women attending sexually transmitted disease clinics. AB - Prevention programs at clinics for sexually transmitted diseases (STDs) have traditionally focused on reducing the spread of STDs through prompt diagnosis and treatment of infections and through notification and treatment of sex partners. For women the clinic examination also offers an opportunity to prevent cervical cancer, a sequela of STDs. Women who have had STDs are at increased risk for cervical cancer, and women who seek health care at public clinics frequently have additional characteristics that place them at risk for not having had a recent Papanicolaou (Pap) smear. Despite the opportunity for cervical cancer screening that is afforded by a visit to an STD clinic, in most public clinics a Pap smear is not part of the routine examination of women. This report summarizes the evidence supporting cervical cancer screening for women with STDs (particularly women attending STD clinics) and addresses the advantages, disadvantages, and net yield of previous screening programs at STD clinics. PMID- 7795114 TI - [Prevention of arteriosclerosis and consumption of olive oil. Is there more to it than its effect on cholesterol?]. PMID- 7795115 TI - [Community-acquired pneumonia in the aged: prognostic factors]. AB - We studied the clinical characteristics and the initial supplementary test available in the emergency service, in aged patients with community-acquired pneumonia, as well as their mortality prognosis value. We assessed 190 patients attended consecutively during one year. Clinical, analytical and radiological data were registered. The parameters associated to a higher mortality were: age, absence of thoracic pain, reduction in the level of consciousness, leukocytosis, increased urea levels, aminotransferases, lactate dehydrogenase and reduction in prothrombin activity and pH. The data associated to a greater relative risk were: age above 80 years, absence of thoracic pain, prothrombin activity lower than 70% and ALT < 40 U/l. The presence of three to four of these variables had a sensitivity of 62% and a specificity of 94% in the prediction of mortality. In the multivariable analysis, the following variables remained significative: age, obnubilation and decrease of prothrombin. We stress the relevance of a high clinical suspicion, given the frequency of these cases with little symptomatology, in order to allow for an early treatment and the identification of right risk patients at the initial assessment. PMID- 7795116 TI - [Cholecystectomy: a choice technique in biliary microlithiasis]. AB - The purpose of our study is to show results obtained after a cholecystectomy on 25 patients in order to present a suggestive clinic of bile origin and a positive result for determination of microcrystals in the bile probe even in the case of negative radiologic diagnoses (echography, cholecystography). Out of 25 patients operated on the following results were obtained: microscopic cholelithiasis in 12, granular cholelithiasis in 3, acute cholecystitis in 2, cholesterolosis in 2 and without pathologic findings in 6 patients after an observation period of 24 months following the operation it was demonstrated that almost all the patients (96%) had no symptoms. On the other hand, the above mentioned results are compared to the findings obtained during an observation period of a group of 34 patients with positive probe results with the same clinic characteristics and not having been operated on refusing the operation suggested. PMID- 7795117 TI - [Abdominal echography in patients with human immunodeficiency virus (HIV) infection. Diagnostic usefulness in the evaluation of associated medico-surgical pathology]. AB - BASIS: The abdominal manifestations in the patient with HIV infection are increasingly frequent. We have conducted the present study in order to determine the diagnostic usefulness of the abdominal echography in the clinical assessment of the patient. MATERIALS AND METHODS: We review the echographic findings of 112 patients carrying the HIV with or without the Acquired Immunodeficiency Syndrome (AIDS). Seventy eight patients were men and 34, women, with an average age of 30 years. The main risk group was parenterally drug addiction (72%). The stage of the HIV infection was IVC1 in 41% of the cases, II in 23%, III in 13% and IVC2 in 13%. The echographic exploration was performed using a real-time echography, with a probe of 3.5 Mhz, assessing according to conventional criteria the abdominal organs and their pathology, masses and free intraabdominal fluid. The echographic characteristics were first broadly assessed in the patients from the series and later on, according to the patient's pathology. (Infectious, acute abdominal, hepatic biochemical disorders, HIV carrier-associated pathology). RESULTS: In 33% of the cases, the echography was normal. Hepatomegaly was the most frequent echographic sign: 56 patients (50%), followed by splenomegaly in 43 patients (38.3%), standing out the affection of the biliary and/or vesicular ductus in 7 patients (6.2%). The echographic findings were not related to the HIV infection stage, nor with the presence of hepatic biochemical disorders. However, the presence of organomegaly (hepatosplenomegaly associated or not to retroperitoneal adenopathies) were more frequent in the group with infectious complication, 33.3% vs 19.6% (p < 0.01), that in the patients without associated infectious processes. In patients with medical or surgical acute abdominal pathology, the echography was diagnostic in 9 out of 10 patients. CONCLUSION: In the HIV patient, the echography allows an specific initial diagnostic assessment, being able in most of the patients with abdominal manifestations to diagnose the causal pathology. PMID- 7795118 TI - [Efficacy and tolerance of doxazosin in the treatment of isolated systolic hypertension in hypertensive patients over 60 years of age]. AB - Isolated Systolic Arterial Hypertension (ISAH) is the most frequent form of AHT in the aged population, resulting in an increase of the cardiovascular risk, mainly at the cerebrovascular level. In this open non-comparative study, we analyze the effect of doxazosin, an alpha-adrenergic blocker in 40 patients older than 60 years, diagnosed of isolated systolic hypertension. After 2 weeks of lavage, the patients received treatment with doxazosin according to a monotherapy scheme, with progressive increase of the dose, from 1 to 16 mg/day during a period of 14 weeks. Doxazosin significantly reduces the systolic and diastolic arterial pressure (p < 0.001) with a therapeutical response in 86.5% of the cases, using an average dose of 3.4 mg/day and without observing modifications in the heart rate. This drug improves the lipidic profile, with a reduction of the plasmatic levels of total cholesterol and cholesterol linked to low density proteins (LDL) with p < 0.05 and a reduction of triglycerides. Among the 40 patients included in the study, 10 (25%) referred side effects; there were 2 drop outs (5%) and the dose had to be reduced in 2 patients (5%). In conclusion, doxazosin shows its antihypertensive effectiveness in the treatment of isolated systolic hypertension in patients older than 60 years and it is well tolerated by most of the patients, improving at the same time the lipidic profile. Hence, it contributes to the reduction of the cardiovascular morbidity-mortality in this group of patients. PMID- 7795119 TI - [Nephrotic syndrome associated with symmetrical multiple lipomatosis (Madelung's disease)]. AB - We present a case of multiple symmetric lipomatosis Type I (Madelung's disease) with severe organic affection, hepatic cirrhosis, sever sensitive polyneuropathy and neuropathic ulceration at the left lower limb. A nephrotic syndrome developed in a larval form due to proliferative glomerulonephritis as the result of a metainfectious complications of the infection at the lower limb. We discuss the etiopathogenicity of the organic affection and we highlight the pathogenic links between the disease and its complications. PMID- 7795120 TI - [Langerhans cell granulomatosis with unifocal bone disease and asymptomatic pulmonary infiltration]. AB - Langerhans' cell granulomatosis is a usually benign disease, characterized by the proliferation of Langerhans' cell containing S-100 protein. Disease is related with the smoking habit and immunological alterations, and is able to affect any organ in isolated or multisystem form. Diagnosis is provided by biopsy of the lesion and bronchoalveolar lavage if the lung is injured. We present a case of a smoker man with lytic lesion in the skull, which biopsy was diagnostic, and with an asymptomatic interstitial infiltrates lungs, with a restrictive spirometry. Remission was achieved with prednisone (0.75 mg x kg) and stop smoking. PMID- 7795121 TI - [Refractory idiopathic liquefying panniculitis]. AB - We present a 28-year-old patient with liquefying idiopathic lobular panniculitis, a variant of the Weber-Christian's disease and intermittent episodes of arthritis in the left foot refractory to sequential treatment with anti-inflammatory drugs, high doses of prednisone, chloroquine, dapsone, colchicine, cyclosporine and methotrexate. PMID- 7795122 TI - [Acute rhabdomyolytic alcoholic myopathy associated with acute alcoholic hepatitis]. AB - Acute rhabdomyolysis (ARM) is a clinico-biological syndrome characterized by the lesion of the skeletal muscle resulting in a disorder of the permeability at the membrane of the muscle cells, with the release of intracellular substances to the plasma, mainly proteins and ions. We present the case of a chronic alcoholic patient which, after a period of several days in which he increased his consumption of alcohol, developed clinical signs of acute rhabdomyolytic alcoholic myopathy (AREM) associated to acute alcoholic hepatitis (AAH). In the review of the literature, we did not find any description of the association between AREM and acute hepatitis of alcoholic origin. We consider the nonspecificity of the clinical signs of the AREM and we suggest the systematic assessment of creatine-phosphokinase in patients at risk. PMID- 7795124 TI - [Collagenous sprue]. PMID- 7795125 TI - [Cefixime in the treatment of lower respiratory tract infections in patients with chronic bronchitis]. PMID- 7795123 TI - [Oxidative stress and infectious pathology]. AB - Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress. PMID- 7795126 TI - [Atypical presentation of Pneumocystis carinii pneumonia]. PMID- 7795127 TI - [Sublingual thyroid tissue and ovarian tumor: is it more than a coincidence?]. PMID- 7795128 TI - [Oxygen therapy in the hospital: a too often incorrect therapy]. PMID- 7795129 TI - [A further case of cervical actinomycosis]. PMID- 7795130 TI - [Coronary vasospasm induced by intravenous adrenaline]. PMID- 7795131 TI - European Self-sufficiency and Haemophilia Prophylaxis: Achievable Goals or Idealistic Concepts? An accord meeting on the future of haemophilia care. PMID- 7795132 TI - Can the supply and demand for plasma-derived products ever be reconciled? Self sufficiency from the viewpoint of a blood transfusion service. AB - Sufficiency is the balance between supply and demand. The problems of estimating future demands and of maintaining adequate supplies of blood for the preparation of blood products, will be discussed from the viewpoint of a well-established blood transfusion service. PMID- 7795133 TI - Can the supply and demand for plasma-derived products ever be reconciled? AB - With regard to self-sufficiency, supply and demand for plasma-derived products can only be reconciled if there is a free exchange of source materials and products with European harmonization of products. It is essential that safety aspects are agreed upon internationally and free access is guaranteed. PMID- 7795134 TI - Is the unpaid/paid donation debate for better or for worse?--advantages of unpaid donations. AB - It is suggested that the best quality blood and blood products are obtained from voluntary unpaid donations as these are given for genuine altruistic reasons. Voluntary donors have no reason to give false information about lifestyle factors which might place them at risk of transmitting infectious agents. There is therefore a reduced risk of obtaining blood during the 'window' period of HIV infection. In addition if a component of a donation transmits an infectious agent, the fractionation plant can be informed to exclude the plasma from that donation or even recall the pertinent blood products. Several countries are already self-sufficient in blood and blood products, based on a voluntary, unpaid donor system. PMID- 7795135 TI - Is the unpaid/paid donation debate for better or for worse?--a commercial viewpoint. AB - The European Association of the Plasma Products Industry represents the private sector member companies that manufacture and provide plasma products throughout Europe. EAPPI believes that the most important aspect of self-sufficiency is a sufficient supply of safe and efficacious product; the question of paid or unpaid donations is of lower importance. To achieve a supply of high quality plasma, EAPPI considers it is necessary to harmonize standards throughout Europe, and suggests a five-point programme towards improving public confidence in the available plasma products. PMID- 7795136 TI - Is self-sufficiency financially viable and ethically justifiable?--the role of the National Blood Authority. AB - The National Blood Authority is committed to the principle of self-sufficiency but also supports the principle of clinical freedom and aims to improve patient care. Methods of increasing plasma yields are being investigated. On-going discussions are being held with the commercial sector concerning the range of products available and methods of improving manufacturing efficiency. It is believed that the NBA can become largely self-sufficient using blood given by the 2,000,000 voluntary donors. PMID- 7795137 TI - Is self-sufficiency financially viable and ethically justifiable?--legal aspects. AB - There is no legislation specifically designed to compensate haemophilia patients who have been damaged by defective blood products. But there is a general regime, created as a result of the thalidomide tragedy, which deals with defective 'products'. It was introduced at the European level by the European Directive on Product Liability in 1985 and has been given effect in England by the Consumer Protection Act 1987. The rights of haemophilia patients who are injured by defective blood products depends on this Directive. PMID- 7795138 TI - Is self-sufficiency financially viable and ethically justifiable?--a commercial viewpoint. AB - Manufacturers of blood products have to maintain the highest possible standards for plasma screening and good manufacturing practices to ensure maximum purity and viral safety. The private sector companies have much experience in implementing and complying with national and international regulations. These requirements involve considerable cost in the areas of (1) plasma collection facilities, (2) research and clinical research, (3) manufacture, and (4) quality control. Total self-sufficiency would mean the loss of many existing resources. An alternative would be a collaboration between the public and private sectors to meet the needs of all patients who require plasma derived products. The current definition of self-sufficiency suggests that it is not financially viable. PMID- 7795139 TI - Should clinical freedom be constrained in the name of self-sufficiency? AB - Clinical freedom should enable a physician to decide in a free and unbiased manner which is the most appropriate therapy to use for a particular patient. In order to implement the four aims of the German Haemophilia Society an average of 4-4.5 units of Factor VIII per capita of the general population per year is needed. At present European countries do not produce this amount, but to reduce the consumption of F VIII in therapy lowers treatment levels. Until plasma collection services in Europe can be expanded it is necessary that the additional, imported, sources of plasma are available, otherwise clinical freedom will be curtailed. PMID- 7795140 TI - Economic issues in European self-sufficiency. AB - Future clinical practice in haemophilia care must make optimum use of resources and provide the highest quality products and services in an efficient and effective manner. Studies show that prophylactic therapy, compared with on-demand therapy, results in less time off work--that is, a smaller loss in productivity. However, prophylactic therapy requires a three- to five-fold greater annual amount of factor VIII than does on-demand therapy. Further study is needed to determine the optimum therapeutic strategy that gives the best cost v. benefit situation. PMID- 7795141 TI - European regulatory issues. AB - Current EU regulations do not cover all aspects of the manufacture and control of blood products. Recent legislation coming into force on 1 January 1995 has established the European Medicines Evaluation Agency and introduced revised systems for approving pharmaceutical products, including blood products. There remains a need for comprehensive harmonized legislation covering plasma collection and screening, virus validation studies, and batch release. PMID- 7795142 TI - Do safety issues of plasma products constrain self-sufficiency? AB - The ultimate responsibility for selecting and administering plasma products to patients rests with the prescribing physician, and it is for him/her to choose the safest product available. However, liability for a product with a full licence rests exclusively with the licence holder. After the problems of HIV and hepatitis C the safety of plasma-derived products has become of paramount importance. Particularly in the public sector, financial, strategic and political obstacles may adversely influence the quantity, quality and safety of plasma collection. The safety of blood products can be substantially enhanced by the harmonization of technical standards across both public and private sectors, thus supporting EC Directive 89/381. Additionally, the goal of European rather than national self-sufficiency should be encouraged. PMID- 7795143 TI - Is haemophilia prophylaxis achievable in the context of self-sufficiency? AB - In Sweden prophylactic treatment in haemophilia was introduced in 1958. Patients receiving prophylactic treatment have less time off school or work, require less hospitalization, have fewer joint bleeds, and generally lead as near normal life as possible. Although prophylaxis is expensive the cost is off-set by the improvement in quality of life and in productivity. At present, Sweden is almost self-sufficient in blood products for prophylactic treatment of haemophiliacs. PMID- 7795144 TI - How will immune tolerance protocols affect self-sufficiency goals? AB - Inhibitor development is a serious complication in haemophilia, and its treatment, immune tolerance therapy, is an expensive part of haemophilia treatment. However, the therapy can lead to an increased lifespan and improved quality of life. If commenced sufficiently early in the disease, it can help to reduce the overall amount of factor VIII concentrate, or other plasma derived therapeutic agents required during life. PMID- 7795145 TI - Will recent innovations in therapy save perceived deficiencies in self sufficiency policies. AB - Future treatment for patients with haemophilia may include the use of either gene therapy, recombinant factor VIII, recombinant factor IX, or high-purity factor IX. Studies on gene therapy are still at the pre-clinical stage, while clinical trials of recombinant factor IX are expected to start by mid-1995. High-purity factor IX concentrates are available and are the treatment of choice for patients with haemophilia B in the absence of a source of recombinant factor IX. Recombinant factor VIII provides a renewable and unlimited source of factor VIII, and is a safe and effective treatment for haemophilia A. PMID- 7795146 TI - A comparison of the European Accord and the Recommendations of the American National Hemophilia Foundation. PMID- 7795147 TI - Self-sufficiency--20 years on. AB - The opening paper of this symposium discusses the theme [European self sufficiency and haemophilia prophylaxis: achievable goals or idealistic concepts?' from four aspects: (a) the meaning and interpretation of self sufficiency in the European Community; (b) a summary of the facts, discussions and developments of the last 20 years; (c) a description of future aims and objectives; and (d) a discussion of what this symposium hopes to achieve. The author suggests that one most important point is to find an adequate definition of the term [self-sufficiency' in this context. PMID- 7795148 TI - Hybrid peptide containing RGDF (Arg-Gly-Asp-Phe) coupled with the carboxy terminal part of alpha 2-antiplasmin capable of inhibiting platelet aggregation and promoting fibrinolysis. AB - The aim of this study was to synthesize and investigate hybrid peptides which contain the RGD (Arg-Gly-Asp) sequence coupled with lysine residues in special arrangements (antiplasmin carboxyterminal peptide) in an effort to simultaneously inhibit platelet aggregation and promote fibrinolysis. The in vitro haemostatic modifying properties of the synthesized peptides were tested by ADP-induced platelet aggregation, plasmin-generation tests and fibrin-clot lysis assays. The hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxyterminal part of antiplasmin (AP26) inhibited platelet activation and increased plasmin generation and in vitro fibrin-clot lysis. PMID- 7795149 TI - Long-term effects of n-3 polyunsaturated fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease. AB - The long-term effects of fish-oil supplementation on haemostatic parameters and bleeding episodes were investigated in patients undergoing coronary artery bypass surgery. They were investigated before and 9 months after the operation. Following randomization postoperatively, 260 patients received 4 g fish-oil concentrate per day, whereas 251 patients comprised the control group. All patients received either aspirin (300 mg/day) or warfarin (international normalized ratio aimed at 2.5-4.2). Compliance was affirmed by determination of serum phospholipid fatty acids. No excess of bleeding episodes could be attributed to the use of fish oil, given in addition to either aspirin or warfarin. The supplementation of fish oil did not affect the bleeding time or plasma levels of beta-thromboglobulin, whereas an increase in the platelet count after the operation was slightly less pronounced in the fish-oil group. Apart from a small increase in PAI-1 antigen of borderline significance, no long-term effects by fish oil on parameters of coagulation and fibrinolysis were seen. PMID- 7795150 TI - Rapid identification of gene defects in protein C deficiency by temperature gradient gel electrophoresis. AB - Protein C deficiency is an autosomally inherited disorder that is associated with a high risk of recurrent venous thrombosis. The authors have shown that temperature gradient gel electrophoresis (TGGE) is a simple and rapid screening method for the detection of mutations in the protein C gene. Samples from eleven patients with sequence defined point mutations in the promoter region of exon I, and in exons II, III, VII, VIII and IX were analysed by TGGE. In all cases the mutations were readily detected. The exons IV, V and VI were not submissive to TGGE analysis due to amplification difficulties. However, specific computer calculations predict a more general applicability of TGGE for the detection of any mutation in the protein C gene. The presented data establish the usefulness of TGGE as a simple and rapid screening method for the detection of hereditary mutations in the protein C gene. PMID- 7795151 TI - The successful removal of a bleeding intracranial tumour in a severe haemophiliac using an adjusted dose continuous infusion of monoclonal factor VIII. AB - Ten per cent of patients with haemophilia A develop intracranial haemorrhage (ICH) with a mortality rate of 30% and an incidence of psycho-neurological sequelae in 50% of survivors. ICH may be spontaneous or in association with trauma and other pathology. The generally recommended management is conservative replacement therapy using bolus injections of factor VIII and no neurosurgical intervention. Adjusted dose continuous infusion therapy provides an alternative method of factor VIII administration that is simple, more cost effective and safer through the maintenance of stable plasma VIII:C levels. This method has been successfully used to cover general surgery and the conservative treatment of subarachnoid haemorrhage but is not widely used due to unfamiliarity with the technique. This paper describes the use of continuous infusion of factor VIII concentrates to cover the successful neurosurgical management of a young man with severe haemophilia A who presented with an ICH associated with a bleeding choroid plexus tumour. Surgery was complicated by the development of a factor VIII inhibitor which disappeared following treatment with an immune-tolerance induction programme. PMID- 7795152 TI - Protein C infusion in a patient with inherited protein C deficiency caused by two missense mutations: Arg 178 to Gln and Arg-1 to His. AB - This paper reports the case of an adult patient with severe protein C(PC) deficiency. She had the first deep vein thrombosis when she was 14 years old and developed skin necrosis when oral anticoagulant treatment was started. The same sequence of thrombotic complications recurred several times. Analysis of the PC gene coding sequences allowed two mutations (Arg-1 to His and Arg 178 to Gln) to be identified in this compound heterozygote. Oral anticoagulant treatment during PC concentrate infusion and low-molecular-weight heparin administration was successful and uncomplicated. PMID- 7795153 TI - Relationship between elevation in the plasma concentration of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and haemostatic parameters during haemodialysis. AB - To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin alpha 2 plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-alpha 1 PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-alpha 1 PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase. PMID- 7795154 TI - Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187. AB - Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC-->GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC-->AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity. PMID- 7795156 TI - A flow dynamic technique used to assess global haemostasis. AB - Global haemostasis was assessed on blood from patients with established blood clotting abnormalities using a hollow fibre flow device. The instrument monitors pressure changes across a polyethylene fibre through which non-anticoagulated whole blood is perfused. This method of analysis is significant because it (1) minimizes or eliminates common problems associated with routine clinical evaluations, such as sample dilution, completion time, and anticoagulant artifacts, (2) rapidly (under 90 min) and accurately calculates in vitro bleeding time (IVBT) and whole blood clotting time (WBCT), (3) presents a reliable means of distinguishing coagulation defects from platelet dysfunction, and (4) reduces the need for a series of screening tests to a single test that requires a small amount of non-anticoagulated whole blood. Using this technology, global haemostasis of normal volunteers was studied using blood samples spiked with PPACK and prostacyclin. Blood from patients with acquired factor VIII deficiency and Glanzmann's thrombasthenia and from those receiving Coumadin therapy were also studied. The hollow fibre device detailed haemostatic abnormalities of both congenital and therapeutic conditions. PMID- 7795157 TI - Fibrin structure and concentration alter clot elastic modulus but do not alter platelet mediated force development. AB - During clot retraction, platelets interact with fibrin resulting in marked reduction of clot volume. Altered fibrin structure has been reported to affect clot retraction as measured by serum expression. This study was performed to test whether such altered retraction was the result of increased resistance to network collapse or due to decreased force development by platelets. Altered fibrin structure was documented as variation of fibre mass/length ratios (mu) and shifts in clot elastic modulus. The force developed by platelets during clotting was measured directly. Increasing the fibrinogen concentration led to thinner fibre formation (decreased mu), and a linear increase in gel elastic modulus. Over a fibrinogen concentration range of 100 to 400 mg/dl, force development was minimally affected. Force development and clot elastic modulus increased in a linear fashion with increasing platelet concentration. Increasing the calcium concentration from 5 to 20 mM caused a 160% increase in fibrin fibre size (mu), and a 52% decline in clot modulus. Force developed at 1200 s declined by 17%. At 15 mg/ml, dextran and hydroxyethyl starch (HES) also increased mu, and decreased clot modulus; however, both agents markedly reduced force development. Increasing ionic strength or the addition of IgG decreased mu and increased gel elastic modulus. Force development increased modestly with increased ionic strength, did not change with addition of IgG in saline and declined with addition of IgG in maltose. This study indicates that force development is primarily dependent on platelet function while clot modulus depends on both fibrin structure and platelet function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795155 TI - No influence of beta-carotene on haemostatic balance in healthy male smokers. AB - A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n = 149) using 20 mg/day beta-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n = 54). Smokers compared with non-smokers had higher fibrinogen (3.5 vs. 3.1 mg/ml, P < 0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03 vs. 6.60 ng/ml, P < 0.05), lower levels of soluble fibrin (3.40 vs. 5.16 micrograms/ml, P < 0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0 vs. 41.3 ng/ml, P = 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n = 77) and beta-carotene (n = 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. beta Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for beta-carotene via a beneficial effect on haemostasis seems improbable. PMID- 7795158 TI - Cytological features of a cystic nodular hidradenoma: potential pitfalls in diagnosis. PMID- 7795159 TI - Adenoid basal carcinoma of the cervix: an unusual cytological appearance. PMID- 7795160 TI - Organotypic thymic carcinoma; case report with histological and cytological correlates. PMID- 7795161 TI - Sclerosing haemangioma of lung mimicking carcinoma diagnosed by fine needle aspiration (FNA) cytology. PMID- 7795163 TI - Cytological changes associated with tubo-endometroid metaplasia of the uterine cervix. PMID- 7795162 TI - Diagnosis by fine needle aspiration cytology of sclerosing haemangioma of the lung. PMID- 7795164 TI - FNA cytology of oncocytic carcinoma of the parotid gland. PMID- 7795165 TI - Cytological scoring system in primary breast cancer. PMID- 7795166 TI - Bancroftian microfilaria in the breast clinically mimicking malignancy. PMID- 7795167 TI - Screening for cervical cancer in developing countries; need for new thinking. PMID- 7795168 TI - Implications of gynaecological abnormalities in pre-selection criteria for cervical screening: preliminary evaluation of 3602 subjects in south India. AB - Early detection and eradication of cervical cancer and its precursor lesions through organized mass cytological screening programmes have recently gained considerable attention in developing countries. Strategies for both cost saving and effective implementation are however required for mass cervical screening in developing countries. In an early cancer detection programme conducted in South India, we analysed cytological abnormalities in 3602 women and correlated the results with other factors, including age, gynaecological complaints, number of years of married life and parity to see if pre-selection for cytologic screening was possible. Only lower grades of dysplasia were found in asymptomatic women below the age of 40 years. In asymptomatic women, malignancy and higher grades of dysplasia were confined to women with a clinically abnormal cervix only. Univariate analysis also revealed that subjects with a parity of more than 3 and a married life of more than 20 years had a significantly higher number of cytological abnormalities. However, on a multivariate analysis the increased number of marital years was not found to be an independent variable. These results suggest that asymptomatic women below the age of 40 years with a married life of less than 20 years and parity below 3, may be excluded from screening campaigns, and that pre-selection for cytologic screening is possible by introducing a programme of clinical and speculum examination of the cervix. PMID- 7795170 TI - Rapid rescreening of cervical smears: an improved method of quality control. AB - Rapid rescreening of approximately 30% of all negative and inadequate consecutive smears was carried out over a 26-month period. Smears (n = 24,012) were rescreened using a x6.3 objective only. Two minutes were allowed for each slide. Thirty-nine smears were found to have been incorrectly diagnosed as negative, a rate of 0.16%. This can be compared with the previous 26 months during which the traditional 1 in 10 random rescreening of unsatisfactory and negative smears had been carried out at a routine pace and with an objective of x10. A total of 6866 smears were rescreened. Eleven were found to have been incorrectly diagnosed as negative, a rate of 0.16%. Rapid rescreening is as sensitive as 1 in 10 rescreening, and allows a greater proportion of smears to be rescreened. We propose rapid rescreening should replace the traditional 1 in 10 rescreening methods. PMID- 7795169 TI - DNA quantification is technically feasible and of value in cervical smear samples: possible applications for determination of progression in low grade dyskaryosis. AB - This study evaluates the feasibility of DNA analysis of cervical intraepithelial neoplasia III (CIN III) lesions on cervical smear and formalin-fixed paraffin embedded tissue (FFPET) blocks with a view to extending this type of analysis to milder grades of dyskaryosis. DNA ploidy was determined by image analysis using a CAS 200 Image Analyser. Seventeen patients with a diagnosis of CIN III were studied. Results show that all smear and tissue samples were non-diploid with nine aneuploid and eight tetraploid lesions. In 6/7 patients whose smears and corresponding biopsies were examined there was complete agreement as to the DNA profile. We conclude that DNA quantification is technically feasible in archival, routinely prepared cervical smears. This technique should now be applied to CINI and CINII cervical smears to determine if it is of value in identifying those lesions that will progress to CIN III. This study is particularly timely with the possibility in the near future of estimation of ploidy by image analysis using instruments such as the Highly Optimized Microscope Environment (HOME) system. PMID- 7795171 TI - The role of Bcl-2 protein and autocrine growth factors in a human follicular lymphoma-derived B cell line. AB - We have shown that the ability of the human follicular lymphoma-derived cell line SU-DHL-6 to proliferate and survive in vitro depends on both Bcl-2 expression and multiple autocrine growth factors. Treatment with Bcl-2 antisense (AS Bcl-2) decreased Bcl-2 protein levels. However, a cytotoxic effect was seen only at very restricted cell densities. Below such densities cells underwent spontaneous death without any treatment, while above these cell densities no cytotoxic effect of AS Bcl-2 could be seen. The conditioned medium of SU-DHL cells supported the survival and growth of these cells cultivated at low cell densities and partially reversed the cytotoxicity associated with Bcl-2 depletion. RT/PCR analysis revealed autocrine expression of IL-1 beta, IL-2, IL-5 and TNF-beta in SU-DHL cells. Neutralizing antibodies against these cytokines inhibited SU-DHL proliferation. Thus, development of autocrine GF secretion may be the second step in the pathogenesis of follicular lymphomas. PMID- 7795172 TI - Identification of differentially glycosylated forms of the soluble p75 tumor necrosis factor (TNF) receptor in human urine. AB - Human urine is known to contain a 30 kDa soluble form of the p75-TNF receptor (sTNF-R2). In this work we have purified sTNF-R2 from the urine of normal subjects and further characterized its structure and activity. sTNF-R2 was resolved by reducing SDS-PAGE in a major band of 30 kDa, similar in size to the previously described urinary sTNFR2, and in a minor band of 45 kDa. "Western" blotting analysis with anti-TNF-R1 and anti-TNF-R2 antibodies showed that both bands were immunologically related to the membrane TNF-R2. Glycosylation studies indicated that the 30 kDa is N-glycosylated while the 45 kDa form is N- and O glycosylated, and suggested that both forms contain terminally linked sialic acid that is differentially recognized by lectins. These results indicate that human urine contains, besides the 30 kDa form, a new form of 45 kDa characterized by different glycosylation type and degree. PMID- 7795174 TI - Endogenous nitric oxide production by human monocytic cells regulates LPS-induced TNF production. AB - The ability to produce nitric oxide (NO) of human monocytes macrophages is object of debate. While studying the regulation of tumor necrosis factor (TNF) synthesis induced by endotoxin (LPS) in a human cell line of monocyte origin (THP-1) and in human peripheral blood mononuclear cells (PBMC) we found an indirect evidence of such production. We showed that L-N-monomethyl-arginine (L-NMMA), an inhibitor of NO synthase, and hemoglobin, a chelator of NO, are able to significantly reduce TNF synthesis, indicating that NO production is induced by LPS and contributes to the induction of TNF. Since NO is a known cytostatic agent, we also studied the cytostatic effect of LPS, and demonstrated that it is reverted by L-NMMA. Although we were unable to show any nitrites/nitrates accumulation in the culture media, taken together our data give an indirect evidence of a physiologically relevant LPS-induced NO production in human monocytes-macrophages. PMID- 7795175 TI - An amplified ELISA for human tumour necrosis factor alpha. AB - An immunoassay for tumour necrosis factor alpha (TNF-alpha) is described using a sandwich system which employs a mouse monoclonal as the capture antibody and a polyclonal rabbit anti-TNF-alpha as the detection antibody. The assay utilises a novel enzyme cycling system to amplify the colourimetric signal generated by alkaline phosphatase in the enzyme immunoassay. The assay sensitivity is increased by the use of the AMPAK system. The detection limit of the assay is in the order of 1 pg/ml which is many times greater than is possible with conventional methods of measurement. The advantages of the enzyme-amplified method will be particularly useful in the quantitative determination of low levels of TNF-alpha in body fluids. This assay system was used to measure peripheral serum TNF levels in a group of women with non-malignant gynaecological conditions, the mean TNF-alpha concentration in these subjects was 10 pg/ml. PMID- 7795173 TI - C-reactive protein-induced colony-stimulating factors production by macrophages. AB - Purified human C-reactive protein(CRP: 0.5-50.0 micrograms/kg) given intravenously to monkeys (Macaca mulatta) induced serum colony-stimulating activity (CSF); maximum induction occurred at 10.0 micrograms/kg. In vitro also, purified human CRP (0.1-50.0 micrograms/ml) stimulated monkey blood monocyte derived macrophages to release CSF in to the medium (CM); 5.0 micrograms/ml CRP appeared optimal. Both in vivo and in vitro, the kinetics of the production of CSF were similar with maximal response occurring 6 h after stimulation and return to background levels by 48 h. Rabbit anti-CRP antibody completely abrogated the production of CSFs in vitro, suggesting a specific interaction between CRP and macrophages. A neutralizing concentration of rabbit anti-human interleukin-1 (IL 1) polyclonal antibody had no effect on CRP induction of CSF-activity, indicating it to be IL-1 independent. CRP-induced CSFs, both in the serum and CM, were functionally similar as they supported the formation of granulocyte (G), macrophage (M) and GM colonies, in similar proportions. The macrophage production of CSFs appeared to be lipopolysaccharide-independent as polymyxin B (25.0 micrograms/ml) had no inhibitory effect. Heat-treated (80 degrees C, 1 h, pH 7.0) CRP did not stimulate the macrophages to produce CSFs. The CSF release was dependent on protein synthesis as it was completely inhibited by cycloheximide (50.0 micrograms/ml). This study demonstrates that purified human CRP can induce the production of serum CSF activity in monkeys, and can stimulate monkey macrophages to produce CSFs in vitro. PMID- 7795176 TI - Protective effect of chlorpromazine on TNF-mediated hapten-induced irritant reaction. AB - Picryl chloride-induced irritant reaction (IR) was shown to be mediated by tumor necrosis factor (TNF). Anti-TNF monoclonal antibodies, but not interleukin 1 receptor antagonist (IL-1 Ra), had a protective effect. Chlorpromazine (CPZ), an inhibitor of TNF synthesis, protected against IR and inhibited the IR-associated TNF induction in ear homogenates. Investigation of the role of polymorphonuclear leukocyte (PMN) in neutropenic mice showed that neutropenia did not prevent the development of the IR. PMID- 7795178 TI - Immunomodulation by cytokine antisense oligonucleotides. AB - The cytokine network is involved in normal immune reaction and in the progression of several pathologies. Antisense (AS) oligonucleotides, which allow specific inhibition of expression of proteins, offer a new methodology to investigate this complex network. This review focuses on the use of AS to modulate cytokine expression. AS may act in different ways such as blocking fixation or progression of the ribosome along the mRNA, mRNA cleavage by RNase H, or preventing normal RNA maturation. In order to improve AS efficiency, chemical modifications have been developed, and improvement of oligonucleotide uptake has been achieved with different systems of vectorization including liposomes (neutral, cationic, immunoliposome), nanoparticles, or covalent attachment of a carrier. In oncogenesis, intracellular or extracellular autocrine loops have been demonstrated by the use of cytokine AS. Involvement of cytokines in immunological reactions (TH1 and TH2 subset, IgE response, lymphokine activated killer, cytotoxic T lymphocyte...) and in hematopoiesis have also been studied with this approach. Therapeutic application of AS has been suggested by inhibition of inflammatory cytokines in vivo. Clinical trials using AS are under investigation in virological and in oncological diseases. At present, cytokine antisenses primarily represent a tool for dissecting the function of a cytokine in vitro, but they may offer in the future a new way for immunomodulation intervention. PMID- 7795177 TI - Measurements of cytokines and their receptors in the brain. International workshop organized within the context of the BIOMED concerted action "Cytokines in the brain". Amsterdam, 21-22 October 1994. PMID- 7795179 TI - High and low surgical procedure rates in census divisions across Canada. AB - This paper identifies outliers (unusually high or low values) among rates of 39 surgical procedures in 255 Canadian census divisions. Surgery rates for the two year period from April 1988 through March 1990 were standardized for age and sex, and then "normalized" to adjust for differences in census division population sizes. Among the 39 procedures, a total of 402 outlying census division rates were found, of which 48 were deemed to be very high, 254 high, 79 low, and 21 very low. The results are presented for individual procedures, by province, and for the 16 census divisions in which medical schools and their associated teaching hospitals are located. PMID- 7795180 TI - Second trimester abortions: trends and medical complications. AB - As a proportion of total abortions, those performed in the second trimester declined from 21% in 1974 to 10% in 1991. Second trimester (13 to 24 weeks) abortions were more frequent among women who were single, under age 20, and without prior deliveries or abortions. The stage of pregnancy at which an abortion was performed and the method used were associated with the risk of medical complications. Complication rates increased directly with the period of gestation. The complication rate for second trimester abortions was 13 times higher than that of first trimester abortions (under 13 weeks). The lowest complication rates were found among abortions performed using surgical D&C and suction D&C. The procedures primarily used for abortions at 16 or more weeks' gestation (i.e. the administration of prostaglandin, urea or saline) were associated with higher complication rates. PMID- 7795181 TI - The Canadian Organ Replacement Register. PMID- 7795182 TI - [The soluble form of guanylate cyclase in the molecular mechanism of the physiological effects of nitric oxide and in regulating platelet aggregation]. PMID- 7795183 TI - [Electrophysiological characteristics of visual perception upon exposure to fluoracizine]. PMID- 7795184 TI - [Discoordination of gastroduodenal myoelectrical activity during immobilization stress in rabbits]. PMID- 7795185 TI - [Relationship of physiological and bioenergetic characteristics of neurotic aged rats]. PMID- 7795186 TI - [Dependence of the antiarrhythmic effect of laser radiation on power, duration, and site of action]. PMID- 7795187 TI - [Increase in sensitivity of mice to a convulsant after adoptive transfer of splenocytes from mice, subjected to corazole kindling]. PMID- 7795188 TI - [Effect of azaleptin and its new derivative seleptin on spontaneous EEG and activation reaction in rabbits]. PMID- 7795190 TI - [Regulatory activity of Kupffer cells in acute blood loss]. PMID- 7795189 TI - [Increase in the resistance of the isolated heart to heat shock while adapting to moderate physical loads]. PMID- 7795192 TI - [The effect of extracorporeal treatment of blood with an ozone-oxygen mixture on lung function of dogs under normal conditions and in disease]. PMID- 7795191 TI - [The role of mast cells in regenerative phenomena in inflammation]. PMID- 7795193 TI - [The effect of the organophosphorus pesticide antio on cerebral blood supply]. PMID- 7795195 TI - [The effect of a hypothalamic cardioactive protein-hormone complex on the cholino sensitivity of the rat small intestine and contraction of the vas deferens]. PMID- 7795194 TI - [Effect of the organophosphorus compound antio on pulmonary and systemic blood circulation in unanesthetized cats]. PMID- 7795196 TI - [Dependence of the regulation of tracheal smooth muscle contractile activity on epithelium]. PMID- 7795197 TI - [Effect of low dose gamma-radiation on nuclear RNA polymerase activity and liver cell protein synthesis in chicks of various ages]. PMID- 7795198 TI - [Some cytochemical features of the motor system of the rat brain after space flight]. PMID- 7795199 TI - [Anti-edemic activity of cerebrocrast in cerebral ischemia]. PMID- 7795200 TI - [Effect of purine antagonists on the cyclic AMP level in lymphocytes and bone marrow lymphoblasts]. PMID- 7795201 TI - [Effect of cerebrocrast on local cerebral circulation and EEG in awake rats in cerebral ischemia]. PMID- 7795202 TI - [Comparison of neurotropic and stress-protective properties of piracetam and the derivative pyrido]1,2-a]pyrimidine]. PMID- 7795203 TI - [The effect of bromantane, a new immunostimulant with psychostimulating action, on release and metabolism of dopamine in the dorsal striatum of freely moving rats: a microdialysis study]. PMID- 7795204 TI - [Correlated interconnection between pharmacokinetic and dynamic development of the pharmacologic effects of bromantane]. PMID- 7795205 TI - [The status of spermatogenesis in rats after administration of the anthracycline antibiotic farmorubicin]. PMID- 7795206 TI - [Immune response to Epstein-Barr virus terminal repeat protein in patients with undifferentiated nasopharyngeal cancer]. PMID- 7795208 TI - [Effect of enriching rations with selenium and vitamin E on some indicators of immunity in rats]. PMID- 7795209 TI - [Effect of lymphokines on platelet cytotoxicity]. PMID- 7795207 TI - [Detection of STLV-1 integration in DNA extracted from formalin-fixed and paraffin-embedded material from M. arctoides lymphoma by the polymerase chain reaction]. PMID- 7795210 TI - [Expression of human interleukin-10 in Escherichia coli cells]. PMID- 7795211 TI - [Differences in the effects of glucocorticoids on beta-adrenergic receptor density in lung and cerebral cortex]. PMID- 7795212 TI - [Informative capacity of the rat sensomotor cortex in the post-reanimation period (a morphometric analysis of neuronal population)]. PMID- 7795213 TI - [Effect of the type of damage on regional changes of some parameters of the endocrine system]. PMID- 7795215 TI - Analysis of optimal conditions for retroviral-mediated transduction of primitive human hematopoietic cells. AB - We sought to define optimal conditions for retroviral-mediated transduction of long-lived human hematopoietic progenitors from bone marrow and peripheral blood. CD34+ cells were transduced by the LN and G2 retroviral vectors in the presence or absence of stromal support and with or without cytokine addition. After transduction, a portion of the cells was plated in methylcellulose colony-forming assay, with or without G418, to assess the extent of gene transfer into committed progenitors. The remaining cells from each experiment were transplanted into immunodeficient mice to allow analysis of transduction of long-lived progenitors. Human colony-forming cells contained within the murine bone marrow were analyzed after engraftment periods of 2 to 11 months. Cells were plated in a human specific colony-forming assay with and without G418 to assess the extent of transduction of primitive progenitors. Individual human colonies were also analyzed by polymerase chain reaction for the presence of provirus. Bone marrow progenitors were efficiently transduced only when stroma was present, whereas mobilized peripheral blood progenitors were effectively transduced in the presence of either stroma or cytokines. Inclusion of the cytokines interleukin-3, interleukin-6, and stem cell factor did not further augment the extent of gene transfer in the presence of a stromal support layer. Additionally, human CD34+ progenitors from bone marrow or mobilized peripheral blood that had been transduced for 3 days in the absence of stroma failed to produce sustained, long term engraftment of bnx mice. Mice transplanted with the same pools of human progenitors that had been transduced in the presence of stroma for 3 days had significant levels of human cell engraftment at the same timepoints, 7 to 11 months after transplantation. Our data show loss of long-lived human progenitors during 3-day in vitro transduction periods in the absence of stromal support. Therefore, the presence of bone marrow stroma has dual benefits in that it increases gene transfer efficiency and is essential for survival of long-lived human hematopoietic progenitors. PMID- 7795217 TI - Variations in radiation sensitivity and repair among different hematopoietic stem cell subsets following fractionated irradiation. AB - The radiation dose-survival of various hematopoietic cell subsets in murine bone marrow (BM) was determined in the cobblestone area forming cell (CAFC) assay under conditions of single-, split-, and multiple-dose irradiation. A greater recovery in cell survival with decreasing dose per fraction, or increasing fraction number, was observed for primitive CAFC day-28 and day-35 than for CAFC day-6 and day-12 (colony-forming unit (CFU)-granulocyte macrophage and CFU-spleen day-12 equivalents). Linear quadratic (LQ) model analysis of CAFC survival data provided an estimate of the alpha/beta ratio that is an inverse index of the fractionation effect and is known to be lower for late than for acutely responding tissues. This analysis gave decreasing alpha/beta ratios with increasing primitiveness of the CAFC subset. These values were found to be comparatively low (about 4 Gy) for CAFC day-28 and day-35 and are in general agreement with previous studies on long-term repopulation in vivo. In contrast, alpha/beta ratios of CAFC day-6 and day-12 were relatively high (above 6 Gy) and are consistent with values obtained from acute marrow failure. Delayed harvesting of BM after a single dose of 6 Gy showed little evidence of proliferative repopulation over 1 week and hence the differential dose-sparing effect of fractionation among the CAFC subsets appears to be mostly attributable to the influence of sublethal damage repair. These results require a reevaluation of previous notions of marrow stem cell radiosensitivity and repair based on acute marrow lethality (LD50/30) or spleen colony (CFU-S) data, especially when applied to fractionated total body irradiation effects on long-term repopulating stem cells in a BM transplant setting. PMID- 7795216 TI - Efficient expression of functional human MDR1 gene in murine bone marrow after retroviral transduction of purified hematopoietic stem cells. AB - A procedure for efficient transfer of the human MDR1 (multi-drug resistance) gene into murine hematopoietic stem cells was developed. Cells expressing Sca-1 but no lineage-specific or major histocompatibility complex (MHC) class II antigens (Lin MHC II-Sca-1+) were enriched from 5-fluorouracil-pretreated bone marrow by Ficoll density-gradient and immunomagnetic sorting. Purified cells were cocultured with growth factors and fibroblasts producing replication-deficient retroviruses containing human MDR1 cDNA. Fluorescence-activated cell sorter analysis and rhodamine-123 efflux experiments showed that greater than 60% of cocultured hematopoietic cells expressed functional human P-glycoprotein. After 6 to 8 days, hematopoietic cells were injected intravenously into sublethally irradiated SCID mice. Stem cell properties of the isolated population were confirmed by sustained expression of MDR1 marker cDNA for greater than 4 to 6 months after transplantation, multilineage engraftment, and presence of MDR1 cDNA in bone marrow of secondary recipient mice after retransplantation. Reconstitution of H 2K-mismatched SCID mice showed high engraftment capacity of Lin-MHC II-Sca-1+ cells. MDR1 cDNA was detected in blood of 78% of recipients. P-glycoprotein was expressed in bone marrow of 71% of mice, in both lymphocytes and myelomonocytoid progenitors. P-glycoprotein function in host marrow was confirmed by rhodamine 123 efflux. Transduction of P-glycoprotein may be useful for gene therapy in two ways: to protect bone marrow from myelosuppression after chemotherapy and as a selectable marker in vivo for the introduction of otherwise nonselectable genes. PMID- 7795214 TI - AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. PMID- 7795219 TI - Murine granulocytic cell adhesion to bone marrow hemonectin is mediated by mannose and galactose. AB - Hemonectin (HN) is a bone marrow (BM) protein that promotes specific attachment of immature granulocytes and their precursors within the BM. We report that HN is a glycoprotein containing both mannose and galactose residues, and provide evidence that these carbohydrates mediate granulocytic cell adhesion to HN. Carbohydrate structure was determined by digoxigenin-conjugated lectin binding to HN and indicated the presence of mannose, galactose, sialic acid, and the absence of fucose-linked oligosaccharides. The role of carbohydrates in mediating cell adhesion was examined by chemical and enzymatic deglycosylation. Deglycosylation of HN with trifluoromethanesulfonic acid, which cleaves N- and O-linked oligosaccharides, inhibits 66% of cell attachment to HN, and results in an apparent decrease in molecular weight from 60 to 50 kD. Enzymatic deglycosylation with endo-B-N-acetylglucosaminidase H, which hydrolyzes specific N-linked mannose residues, inhibits 30% of cell adhesion to HN. Finally, the role of these specific sugars in hemonectin-mediated cell adhesion was confirmed with neoglycoprotein blocking. Preincubation of BM cells with mannosyl- and galactosyl BSA probes produces a dose-dependent inhibition of cell attachment to HN, whereas fucosyl-BSA does not inhibit cell adhesion to HN. These results show that mannose and galactose partially mediate adhesion of BM granulocytes to HN. PMID- 7795218 TI - Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures. AB - Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential-colony forming cells [HPP-CFC], long-term culture initiating cells [LTC-IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40-fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment. PMID- 7795220 TI - The human leukocyte integrin CD11a promoter directs expression in leukocytes of transgenic mice. AB - The human CD11a molecule is expressed specifically on lymphocytes, monocyte/macrophages, and neutrophils, in which it mediates important adhesion related functions. We used 1.7 kb of regulatory sequences upstream from the human CD11a gene transcription start site to drive expression of a modified human CD4 reporter gene in transgenic mice. The transgene was expressed in a tissue specific fashion on all leukocytes and paralleled endogenous mouse CD11a expression. All five founder mice expressed the transgene, providing evidence for integration site-independent expression. However, expression was not proportional to transgene copy number. These studies indicate that (1) the mutated human CD4 serves as an excellent reporter for analysis of leukocyte-specific promoters; (2) the CD11a regulatory unit used here represents a novel reagent for targeting gene expression to leukocytes; and (3) additional regulatory regions will be required for copy-number-dependent activity of CD11a regulatory sequences. PMID- 7795221 TI - Primary familial polycythemia: a frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin. AB - Primary familial and congenital polycythemia (PFCP) is characterized by erythrocytosis with normal arterial PO2, blood P50, and serum erythropoietin (EPO) levels. In two PFCP families EPO receptor (EPOR) polymorphisms cosegregated with PFCP. A heterozygous insertion of G at EPOR nucleotide 5975 was identified in genomic DNA from polycythemic members of family no. 2. 5974insG shifts the reading frame at codon 430, predicting amino acid substitutions and truncation of the last 64 amino acids. Wild-type and mutant EPOR transcripts were detected in erythroid progenitors from affected individuals. Burst-forming units-erythroid from patients exhibited increased colony size and sensitivity to EPO. Transfected Ba/F3 cells expressing EPOR 5974insG exhibited increased EPO sensitivity compared with cells expressing wild-type EPOR. The functional effect of this EPOR mutation was directly compared with the other C-terminal mutations reported in unrelated PFCP families by expression in Ba/F3 cells. The transfected cells with another primary polycythemia associated EPOR mutant construct (G6002A) also exhibited increased sensitivity to EPO. PMID- 7795222 TI - Initiation of hematopoiesis and vasculogenesis in murine yolk sac explants. AB - The blood islands of the visceral yolk sac (VYS) are the initial sites of hematopoiesis in mammals. We have developed a yolk sac explant culture system to study the process of blood cell and endothelial cell development from extraembryonic mesoderm cells. No benzidine-positive cells or beta H1-globin mRNA expression was detected at the primitive streak or neural plate stage of development (E7.5). However, when isolated E7.5 dissected tissues were cultured for 36 to 72 hours in serum-free medium, hundreds of hemoglobin-producing cells and embryonic globin gene expression were identified in both intact yolk sac and VYS mesoderm explants. Explanted E7.5 extraembryonic mesoderm tissues thus recapitulate in vivo primitive erythropoiesis and do not require the presence of a vascular network or the VYS endoderm. Yolk sac blood islands also contain endothelial cells that arise by vasculogenesis and express flk-1. We detected flk 1 mRNA as early as the primitive streak stage of mouse embryogenesis. Culture of embryo proper and intact VYS explants, which contain both mesoderm and endoderm cells, produced capillary networks and expressed flk-1. In contrast, vascular networks were not seen when VYS mesoderm was cultured alone, although flk-1 expression was similar to that of intact VYS explants. The addition of vascular endothelial growth factor to VYS mesoderm explants did not induce vascular network formation. These results suggest that the VYS endoderm or its extracellular matrix is necessary for the coalescence of developing endothelial cells into capillary networks. PMID- 7795223 TI - Circulation of human hematopoietic cells in severe combined immunodeficient mice after Cl2MDP-liposome-mediated macrophage depletion. AB - Intravenous injection of dichloromethylene diphosphonate (Cl2MDP) encapsulated in liposomes results in specific elimination of macrophages in the spleen and liver of normal mice. Severe combined immunodeficient (SCID) mice were treated with Cl2MDP-liposomes followed by injection of human peripheral blood leukocytes. Control SCID mice had no detectable human cells within 72 hours as determined by fluorescence-activated cell sorting (FACS) analysis. However, Cl2MDP-liposome treated animals maintained a large proportion (%) of human cells in peripheral blood and spleen for at least 12 days. Cl2MDP-liposome-injected SCID mice that had previously been implanted with human fetal thymus and liver showed a transient increase in human cell content in peripheral blood, and an accumulation of human cells specific to the white pulp of the spleen. These results indicate that murine mononuclear phagocytic cells may play an important role in the clearance of human cells injected intravenously or generated endogenously in SCID mice and that Cl2MDP-liposome-mediated macrophage depletion allows human hematopoietic cells to circulate and survive in SCID mice, thereby expanding the potential for studying human cellular processes in vivo. PMID- 7795224 TI - Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist stimulated human platelets. AB - Sphingosine-1-phosphate (Sph-1-P) is the initial product of catabolism of sphingosine by sphingosine kinase and is cleaved by Sph-1-P lyase to a fatty aldehyde and ethanolamine phosphate. This phosphorylated sphingoid base is not only an intermediary catabolite, but also a bioactive lipid with important functions, including stimulation of cell proliferation in Swiss 3T3 fibroblasts and inhibition of tumor cell motility. In the present study, we examined functional roles of Sph-1-P in human platelets. Sph-1-P induced platelet shape change and aggregation reactions, although it failed to elicit secretion. Sphingosine, ceramide, sphingomyelin, and N,N-dimethylsphingosine did not mimic the positive effects of Sph-1-P on platelets. Subthreshold concentrations of Sph 1-P and weak platelet agonists such as adenosine diphosphate (ADP) and epinephrine synergistically elicited aggregation, which may be important for efficient amplification of platelet activation. Sph-1-P induced intracellular Ca2+ mobilization and the dose-response for Ca2+ release correlated closely with the concentration required for induction of shape change. On addition of [3H]sphingosine to intact platelets, the label was rapidly converted to Sph-1-P, and subsequently to ceramide and sphingomyelin. Interestingly, the Sph-1-P formed was specifically released into medium on stimulation of platelets with physiologic agonists. The amount of Sph-1-P in platelets, as measured by its conversion into radiolabeled N-acetyl-Sph-1-P, was 1.4 nmol/10(9) cells and was about four times higher than the mass of Sph present. When compared by mole percent Sph-1-P/phospholipid, the value for platelets is over 10 times higher than that for neutrophils. Our results suggest that Sph-1-P, rapidly converted from sphingosine, abundantly stored in platelets, and released on the cell activation, may play a physiologic role in thrombosis, hemostasis, and the natural wound-healing processes. PMID- 7795226 TI - Retinoic acid reduces induction of monocyte tissue factor and tissue factor/factor VIIa-dependent arterial thrombus formation. AB - Agents that downregulate the induction of monocyte/macrophage tissue factor (TF) activity may attenuate the thrombotic risk associated with mechanical restoration of vessel patency or artificial arterial grafting. In such events, procoagulant macrophages in the atherosclerotic plaque and procoagulant monocytes adherent to artificial materials may be exposed to the blood stream. Ishii et al (Blood 80:2556, 1992) reported that induction of endothelial TF is downregulated by all trans retinoic acid (ATRA), and Conese et al (Thromb Haemost 66:662, 1991) reported that retinoids downregulate monocyte procoagulant activity (PCA). These findings led us to investigate the effect of ATRA on monocyte TF expression, and to study the effect of ATRA on monocyte-induced thrombus formation in a model system of human arterial thrombogenesis. Induction of PCA in human peripheral blood monocytes by 0.5 microgram/mL lipopolysaccharide (LPS) was dose dependently reduced by ATRA, reaching a reduction of 56% at 10(-5) mol/L ATRA (P < .0001). A 38% reduction (P < .0007) in LPS-induced TF antigen expression was observed at an ATRA concentration of 10(-6) mol/L. Adherence of monocytes to plastic cover slips (Thermanox, Miles Laboratories, Naperville, IL) also triggered induction of cellular PCA, which was inhibited by more than 80% by an anti-TF monoclonal antibody (MoAb) (P < .002). Inclusion of ATRA (10(-6) mol/L) reduced this PCA by 40% (P < .03), and the TF antigen expression by 30% (P < .0001). Exposure of Thermanox adherent monocytes to flowing nonanticoagulated human blood in a parallel-plate perfusion chamber device at an arterial wall shear rate of 650 s-1 elicited significant fibrin deposition and platelet thrombus formation. Partial interruption of this thrombus formation was achieved by 10(-6) mol/L ATRA, which reduced the fibrin deposition by 80% (P < .02) and platelet thrombus formation by 50% (P < .05). In comparison, incubation of adherent monocytes with the anti-TF MoAb before the blood exposure, reduced the fibrin deposition by 83% (P < .02) and platelet thrombus volume by 75% (P < .0008). Thus, ATRA is an effective down regulator of monocyte TF-PCA, and may reduce thrombotic complications at sites of plaque rupture, at plaque disruption after percutaneous transluminal angioplasty procedures, or on surfaces introduced by artificial arterial grafting. PMID- 7795225 TI - Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. AB - The receptor for urokinase plasminogen activator (uPA-R, CD87) is a glycosylphosphatidylinositol (GPI)-anchored 50 to 65 kD glycoprotein that, by regulating membrane-associated plasmin activity, may facilitate the invasion of inflammatory and malignant cells. Certain other GPI-anchored glycoproteins are shed from the cell membrane and exist as soluble products in vitro and in vivo. To determine if uPA-R undergoes a similar phenomenon, we have developed a sensitive enzyme-linked immunoabsorbent assay (ELISA) (using a rabbit antiserum as both capture and detection reagents) to measure the quantity of soluble uPA-R (suPA-R) in tissue culture supernatants and biologic fluids. Using this ELISA, we have detected suPA-R in the culture supernatants of U-937 cells and human monocytes stimulated in vitro by certain soluble inflammatory mediators (Sitrin et al, Blood 84:1268, 1994; Mizukami et al., Clin Res 42:115A, 1994). To determine if suPA-R exists in vivo, we have screened the plasma of 20 normal volunteers (mean +/- SD, 3 +/- 3 ng/mL; median, 2 ng/mL; range, 1 to 11 ng/mL [serum values slightly higher]); the plasma of 13 ICU patients with clinical sepsis syndrome (mean +/- SD, 30 +/- 11 ng/mL; median, 11 ng/mL; range, 4 to 221 ng/mL); and the extravascular fluids (pleural, pericardial, and peritoneal) of 84 individuals with presumed inflammatory or malignant conditions (mean +/- SD, 21 +/- 39 ng/mL; median, 10 ng/mL; range, 2 to 253 ng/mL). Among the latter specimens, most were inflammatory exudates (only six were malignant by positive cytology) with the highest quantities of suPA-R associated with neutrophilic exudates. The solubility of suPA-R contained within these fluids was confirmed by reanalysis after ultracentrifugation to remove particulate material. When tested in a uPA ligand capture ELISA, representative specimens of extravascular body fluids and sepsis plasma contained suPA-R capable of binding uPA ligand (generally representing a small fraction of the immunoreactive material). We conclude from these data that suPA-R is immunologically detectable in vitro and in vivo with high concentrations of receptor found under conditions of inflammatory stimulation. The possibility of suPA-R's biologic activity is suggested by its partial retention of ligand binding capacity. PMID- 7795227 TI - Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. AB - Because multiple risk factors in one patient may increase the clinical expression of thrombophilia, we assessed the presence in protein C-deficient patients of the factor V Arg 506 Gln mutation responsible for activated protein C resistance. Using a strategy allowing rapid screening of factor V exon 10, we studied 113 patients with protein C deficiency and 104 healthy volunteers. We detected the Arg 506 Gln mutation in 15 patients (14%) and in one healthy subject (1%). We identified a previously unpublished sequence variation leading to an Arg 485 Lys substitution in three normal subjects and seven protein C-deficient patients. A significant difference in the allelic frequency of the Arg 506 Gln factor V mutation was found between protein C-deficient patients heterozygous for an identified protein C mutation (n = 84; allelic frequency, 4.8%) and protein C deficient patients with no identified mutation in the protein C gene coding regions (n = 25; allelic frequency, 14%). The results demonstrate that a significant subset of thrombophilic patients has multiple genetic risk factors although additional secondary genetic risk factors remain to be identified for the majority of symptomatic protein C-deficient patients. PMID- 7795228 TI - The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells. AB - Thrombomodulin (TM) is an anticoagulant endothelial cell surface glycoprotein containing six tandem epidermal growth factor (EGF)-like structures. We prepared a recombinant TM peptide (rTME1-6, from R214GHWA to DSGK466 of native TM) composed of these six EGF-like structures and investigated the effect of rTME1-6 peptide on the growth of the Swiss 3T3 fibroblast cell line. It was found that rTME1-6 induced proliferation of Swiss 3T3 cells and accelerated [3H]thymidine uptake into their DNA. [3H]Thymidine uptake increased in a dose-dependent manner, plateauing at 50 ng/mL rTME1-6, which was 1.8 times the control level. rTME1-6 peptide (50 ng/mL) also accelerated the DNA synthesis of human dermal fibroblasts (HDFs), A549 (a human lung cancer cell line), HepG2 (a human hepatocarcinoma cell line), and U937 cells (a human monocytic cell line) to 1.5, 1.6, 1.4, and 1.2 times the control level, respectively. The magnitude of the acceleration of DNA synthesis in Swiss 3T3 induced by rTME1-6 was approximately 20% of that of EGF on a molar basis. The uptake of [3H]thymidine was accelerated synergistically by coculture of the cells with rTME1-6 and insulin, similar to the coculture with EGF and insulin. The effects of rTME1-6 were abolished by addition of polyclonal antihuman TM IgG, whereas the actions of insulin and EGF were not influenced. Glucose uptake in Swiss 3T3 cells also increased 1.6 times over control levels by culture with 50 ng/mL rTME1-6 (1.25 nmol/L), compared with 2.7 times by 10 ng/mL EGF (1.66 nmol/L). Binding of [125I]EGF (0.5 ng/mL, 0.083 nmol/L) by the cells was inhibited by about 60% by addition of an eight-fold molar excess of nonlabeled EGF (0.664 nmol/L), whereas no inhibition of [125I]EGF binding was observed, even in the presence of a 1,000-fold molar excess (83 nmol/L) of rTME1 6. Specific binding of [125I]rTME1-6 on the cells showed a saturation curve, and the apparent concentration of rTME1-6 required for half maximum binding of the peptide on the cells was calculated to be 31.5 ng/mL. Thus, the overall results indicated that the rTME1-6 peptide had mitogenic activity for Swiss 3T3 cells, accelerated DNA synthesis and glucose uptake, and that the mitogenic activity might be mediated by binding of the peptide to a specific site different from the EGF receptor. PMID- 7795229 TI - Recombinant thrombopoietin induces rapid protein tyrosine phosphorylation of Janus kinase 2 and Shc in human blood platelets. AB - A cDNA for the thrombopoietin has been cloned by several groups. The recombinant thrombopoietin has been reported to stimulate the megakaryocytopoiesis and thrombopoiesis. Little is known regarding the molecular basis of its effects. To elucidate the molecular mechanism involved in signal transduction, we have investigated the effects of thrombopoietin on platelet tyrosine phosphorylation. We report here that thrombopoietin induced time- and dose-dependent tyrosine phosphorylation of several proteins including Janus kinase 2 (Jak2) and a 52-kD protein, Shc, in human blood platelets. Both Jak2 and Shc were tyrosine phosphorylated within 15 seconds after stimulation. The tyrosine phosphorylation of Jak2 was accompanied by increased kinase activity, whereas Shc tyrosine phosphorylation induced its association with a 25-kD protein, Grb2. Thus, our data suggest that Jak2, Shc, and Grb2 may be involved in signal transduction after ligand binding to c-mpl in human platelets. PMID- 7795230 TI - Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes. AB - The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1 induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies. PMID- 7795231 TI - Increased levels of oxidized glutathione in CD4+ lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection. AB - We investigated the intracellular glutathione redox status in isolated lymphocyte subpopulations and monocytes in patients with human immunodeficiency virus type 1 (HIV-1) infection and in healthy controls. CD4+ lymphocytes from HIV-1-infected patients were primarily characterized by a substantial increase in oxidized glutathione levels and a considerable decrease in the ratio of reduced to total glutathione, in most cases below 0.5 in patients with symptomatic HIV-1 infection, rather than decreased levels of reduced glutathione. The increase in oxidized glutathione was strongly correlated with low numbers of CD4+ lymphocytes in peripheral blood and impaired stimulated interleukin-2 production and proliferation in peripheral blood mononuclear cells, which is compatible with an immunopathogenic role for these redox disturbances. The HIV-1-infected patients with the most advanced clinical and immunologic disease were also characterized by an increase in levels of reduced glutathione in monocytes, suggesting that the glutathione redox cycle may be differentially regulated in CD4+ lymphocytes and monocytes. We could not confirm previous reports suggesting cysteine deficiency as a major cause of disturbed glutathione homeostasis during HIV-1 infection. The demonstrated glutathione abnormalities were correlated with raised serum levels of tumor necrosis factor alpha. These findings suggest that a therapeutical approach, which can restore the glutathione redox dysbalance in CD4+ lymphocytes and decrease the inflammatory stress, may be worthwhile exploring in HIV-1 infection. PMID- 7795232 TI - Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. AB - Cell-cycle kinetics were measured in situ after infusions of iododeoxyuridine and/or bormodeoxyuridine in 50 patients with myelodysplastic syndromes (MDS) and the median labeling index in bone marrow (BM) biopsy samples was 28.6%. Unfortunately, 26 of 50 patients showed that > or = 75% of hematopoietic cells of all three lineages were undergoing programmed cell death (PCD) in their biopsy samples as shown by the in situ end labeling (ISEL) technique. Ten patients had 1/3 and eight had 2/3 ISEL+ cells. Stromal cells were frequently ISEL+ and often S-phase cells were also found to be simultaneously ISEL+. Nucleosomal DNA fragments as a ladder in agarose gel were present in BM aspirates of four patients who showed high ISEL and were absent in two who had no ISEL staining in biopsy samples, but only when DNA was extracted after a 4-hour in vitro incubation in complete medium. Therefore, laddering data confirmed the ISEL findings that the majority of hematopoietic cells in MDS are in early stages of PCD. We conclude that extensive intramedullary cell death may explain the paradox of pancytopenia despite hypercellular marrows in MDS patients. Investigating approaches that protect against PCD in some MDS subsets would be of interest. PMID- 7795233 TI - RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts. AB - As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16;16)(p13;q22) has been shown to result from the fusion of transcription factor subunit core binding factor (CBFB) to a myosin heavy chain (MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase polymerase chain reaction (RT-PCR). In all of 27 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in frame fusion protein was detected. In a more extensive RT-PCR analysis with different primer pairs, we detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 patients tested. The CBFB-MYH11 reading frame of the second transcript was maintained in one patient but not in the others. We show that the different CBFB-MYH11 transcripts in one patient arise from alternative splicing. Translation of the transcript in which the CBFB-MYH11 reading frame is not maintained leads to a slightly truncated CBFB protein. PMID- 7795234 TI - BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts. AB - The BCL-6 gene is known to be located on chromosome 3q27, at the breakpoint of the 3q27-associated translocations that occur frequently in human non-Hodgkin's lymphomas (NHLs). To identify the BCL-6 protein, two antibodies that recognized distinct domains of this protein were raised in rabbits. Immunoprecipitation and immunoblotting of lysates of BCL-6-expressing cells using both antibodies showed a broad 92- to 98-kD band. Dephosphorylation of BCL-6 protein reduced the size of this band to 87 kD, suggesting that BCL-6 may be expressed in a phosphorylated form. Immunostaining with both antibodies showed that BCL-6 protein was localized in the nuclei of most of the germinal center B cells and a small number of marginal zone B cells. Furthermore, BCL-6 protein was expressed in follicular, Burkitt's, and diffuse large B-cell lymphomas. These results suggest that the BCL 6 protein, expressed in B cells of the germinal centers which are important in the maturation of immune responses, may play some physiological role(s) in the germinal center B cells. PMID- 7795236 TI - Overexpression of cyclin D1 in the Dami megakaryocytic cell line causes growth arrest. AB - The maturation of megakaryocytes in vivo requires polyploidization or repeated duplication of DNA without cytokinesis. As DNA replication and cytokinesis are tightly regulated in somatic cells by cyclins and cyclin-dependent kinases, we sought to determine the pattern of cyclin gene expression in cells that undergo megakaryocytic differentiation and polyploidization. The Dami megakaryocytic cell line differentiates and increases ploidy in response to phorbol 12-myristate 13 acetate (PMA) stimulation in vitro. We used Northern blotting to analyze mRNA levels of cyclins A, B, C, D1, and E in PMA-induced Dami cells and found that cyclin D1 mRNA levels increased dramatically (18-fold). Similar increases in cyclin D1 mRNA were obtained for other cell lines (HEL and K562) with megakaryocytic properties, but not in HeLa cells. The increase in cyclin D1 was confirmed by Western immunoblotting of PMA-treated Dami cells. This finding suggested that cyclin D1 might participate in megakaryocyte differentiation by promoting endomitosis and/or inhibiting cell division. To address these possibilities, we constructed two stable Zn+2-inducible, cyclin D1-overexpressing Dami cell lines. Cyclin D1 expression alone was not sufficient to induce polyploidy, but in conjunction with PMA-induced differentiation, polyploidization was slightly enhanced. However, unlike other cell systems, cyclin D1 overexpression caused cessation of cell growth. Although the mechanism by which cyclin D1 may affect megakaryocyte differentiation is not clear, these data demonstrate that cyclin D1 is upregulated in differentiating megakaryocytic cells and may contribute to differentiation by arresting cell proliferation. PMID- 7795235 TI - Identification of B-cell growth factors (interleukin-14; high molecular weight-B cell growth factors) in effusion fluids from patients with aggressive B-cell lymphomas. AB - The molecular basis of neoplastic B-cell growth is complex and poorly understood. Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction, but little is known about the in vivo role of these growth factors. We have examined the production of interleukin 14 (IL-14) (high molecular weight [HMW], B-cell growth factor [BCGF]) by aggressive intermediate (diffuse large cell) lymphomas of the B-cell type non Hodgkin's lymphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots and IL-14 mRNA was constitutively expressed in the freshly isolated lymphoma cells that also expressed the receptor for IL-14 (IL14R). Lymphoma B cells placed at low serum and cell density proliferated in vitro to either purified IL-14 or IL-14 derived from effusion fluids. Antibodies to IL-14 removed the growth-stimulating cytokine(s) from the effusions. Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro. Thus, autocrine or paracrine production of IL-14 may play a significant role in the rapid proliferation of aggressive NHL-B. Interrupting this pathway could be a useful goal of therapy for patients resistant to conventional chemotherapy. PMID- 7795237 TI - Cutaneous T-cell infiltrates: analysis of T-cell receptor gamma gene rearrangement by polymerase chain reaction and denaturing gradient gel electrophoresis. AB - In cutaneous T-cell infiltrates, the demonstration of a clonal T-cell receptor (TCR) gene rearrangement has been considered helpful to distinguish Cutaneous T cell lymphomas from reactive lymphoproliferation. Hence, a polymerase chain reaction (PCR) method using GC-clamp primers and denaturing gradient gel electrophoresis has been developed in our laboratory to analyze the TCR gamma locus configuration. Two hundred eleven cutaneous samples from 155 patients were analyzed. A detectable clonal TCR gamma rearrangement was significantly associated with cutaneous T-cell lymphomas as defined by morphologic and immunologic criteria. A clonal TCR gamma rearrangement was also detected frequently in lymphomatoid papulosis, never in reactive lymphocytic infiltrates and B-cell lymphomas, and rarely in parapsoriasis en plaque and cutaneous lymphoid hyperplasia. Forty five patients had both a cutaneous and a peripheral blood sample. Fifteen had a detectable clonal rearrangement in the two samples and 22 were negative. Six patients had a positive skin sample and a negative blood sample, whereas two patients had a positive blood sample and a negative skin sample. Four lymph node samples were analyzed and the PCR results were the same as in the skin. Finally, 21 patients had sequential samples of recurrent skin lesions. The PCR results were concordant in all and, when detectable, the clonal TCR gamma rearrangement remained unchanged in a given patient. Because of its simplicity and accuracy, the newly designed PCR procedure improves the monitoring of diagnosis, staging, and follow-up in cutaneous T-cell infiltrates. PMID- 7795239 TI - Magnetic resonance imaging of femoral marrow in patients with myelodysplastic syndromes or leukemia. AB - We evaluated magnetic resonance imaging (MRI) of femoral marrow in 85 untreated adult patients with myelodysplastic syndromes (MDS) (N = 27), aplastic anemia (N = 9), and leukemia (N = 49). Images of femoral marrow were obtained using a T1 weighted spin-echo (SE) method and a short T1 inversion recovery (STIR) technique. In patients with MDS, the change in MRI pattern from a fatty or nodular pattern to a uniform pattern correlated with disease progression. Evolution to acute leukemia in MDS patients was associated with a higher signal intensity on STIR images (lower signal intensity on T1-weighted SE images) and an extended area of involvement. The femoral marrow in patients with de novo acute myeloid leukemia (AML) showed increased signal and varied patterns (scattered to uniform) on STIR images. However, the faint pattern (grade 4a) was characteristic of M2 AML. In patients with chronic myelogenous leukemia (CML) in the chronic phase, increased leukemic mass was represented by replacement of the femoral marrow with a region of abnormal signal intensity. The extent of involved areas in these CML patients correlated with the spleen size. This study indicates that MRI of femoral marrow is an important tool for the accurate diagnosis and management of patients with MDS and leukemia that may function as an adjunct to bone marrow aspiration and biopsy. PMID- 7795238 TI - p16INK4A and p15INK4B gene deletions in primary leukemias. AB - The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene. PMID- 7795240 TI - Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia. AB - Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation--GATA-1, EPOR, alpha-globin, beta-globin, and gamma-globin genes- in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a minority of the gamma-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high gamma globin:beta-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells. PMID- 7795241 TI - AG dinucleotide insertion in a patient with chronic granulomatous disease lacking cytosolic 67-kD protein. AB - The 67-kD cytosolic protein (p67-phox) is an essential component of the superoxide-generating system in phagocytes, and its defect is known to cause chronic granulomatous disease (CGD). We sequenced p67-phox cDNA from one of seven patients found in Japan and his parents. In the patient's cDNA, homozygous AG dinucleotide insertion at position 399 (or 401) was found together with three other homozygous substitutions in a coding region (A-542 to G, T-895 to C and A 983 to G) compared with the sequence reported for HL-60 cells. In cDNA from his parents, the AG insertion was found to be heterozygous. In contrast, the other three substitutions were found homozygously in his father's specimen and the latter two in his mother's specimen. The substitution of A-542 to G was heterozygous in his mother's cDNA. The AG insertion would induce a frame shift and bring about a stop codon at the position of 433. However, the other three differences would give insignificant changes for the protein function, if any, because the substitutions of A-542 to G and A-983 to G result in the conservative amino acid transitions, ie, Lys-180 to Arg and Lys-327 to Arg, and that of T-895 to C no amino acid change. Neutrophils from the patients completely lacked superoxide generating activity whereas those from his parents generated substantial amounts of superoxide anion upon stimulation. Thus, it is concluded that the AG dinucleotide insertion is responsible for the disease in this patient. PMID- 7795242 TI - Generation of normal human red cell volume, hemoglobin content, and membrane area distributions by "birth" or regulation? AB - Using flow cytometry and osmotic lysis measurements, we document here the means and coefficients of variation of the following red cell (RBC) properties: hemoglobin (Hb) content, volume, Hb concentration, and relative lytic tonicity distributions in populations of normal human RBCs, before and after density fractionation. The distributions showed a pattern characterized by much larger coefficients of variation of the Hb content and volume distributions than of the Hb concentration and relative lytic tonicity distributions. From analysis of the factors that determine those RBC properties, the patterns were interpreted as reflecting previously unrecognized statistical proportionalities between cell osmolyte content, Hb content, and membrane area. The possible origin of these statistical links was analyzed by considering alternative models with and without the participation of regulatory processes during cell maturation. A model was shown to be feasible in which mature RBC variability with proportional volume, area, and Hb content arises solely from cell size variability at the last erythroid cell division. PMID- 7795243 TI - Perturbation of red blood cell membrane rigidity by extracellular ligands. AB - It is known that binding of extracellular antibodies against the major sialoglycoprotein, glycophorin A, reduced the deformability of the red blood cell membrane. This has been taken to result from new or altered interactions between the glycophorin A and the membrane skeleton. We have shown by means of the micropipette aspiration technique that antibodies against the preponderant transmembrane protein, band 3, induce similar effects. A definite but much smaller reduction in elasticity of the membrane is engendered by univalent Fab fragments of the anti-band 3 antibodies. By examining cells genetically devoid of glycophorin A or containing a variant of this constituent, truncated at the inner membrane surface, we have shown that the anti-band 3 antibodies do not act through the band 3-associated glycophorin A. We examined the effect of anti glycophorin A antibodies on homozygous Wr(a+b-) cells, in which an amino acid replacement in band 3 annihilates the Wright b (Wrb) epitope (comprising sequence elements of glycophorin A and band 3) and thus, by implication disrupts or perturbs the band 3-glycophorin A interaction; these cells show a much smaller response to an anti-glycophorin A antibody than do normal controls. We infer that in this case anti-glycophorin A antibodies exert their rigidifying effect through the associated band 3. Another anti-glycophorin A antibody, directed against an epitope remote from the membrane surface, however, increases the rigidity of both Wr(a+b-) and normal cells. This implies that not all antibodies act in the same manner in modifying the membrane mechanical properties. The effect exerted by anti-band 3 antibodies appears not to be transmitted through the band 3-ankyrin spectrin pathway because the rigidifying effect of the intact antibody persists at alkaline pH, at which there is evidence that the ankyrin-band 3 link is largely dissociated. The large difference between the effects of saturating concentrations of the divalent and univalent anti-band 3 antibodies implies the existence of an overriding effect on rigidity, resulting from the bifunctionality of the intact antigen. Freeze-fracture electron microscopy shows that the anti band 3 promotes the formation of small clusters of intra-membrane proteins. Extracellular ligands may in general act by promoting strong or transient interactions between integral membrane proteins, thereby impeding local distortion of the membrane skeletal network in response to shear. PMID- 7795244 TI - Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton. AB - Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3 Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation. PMID- 7795245 TI - Hemoglobin-spectrin complexes: interference with spectrin tetramer assembly as a mechanism for compartmentalization of band 1 and band 2 complexes. AB - The irreducible complexation of hemoglobin with spectrin is a natural phenomenon of red blood cell aging, positively correlating with increasing cell density and decreasing cell deformability. The current study begins to address the role of these complexes in the disruption of membrane skeletal physiology and structure. The effect of bound hemoglobin on spectrin dimer self-association was investigated in vitro. The extent of conversion of isolated spectrin dimers to tetramers was evaluated as a function of peroxide-induced globin complexation before the conversion incubations. The incremental accumulation of tetramer was observed to decrease with increasing peroxide concentration used in the globin complexation step. The role of oxidized heme in this process was made apparent by the inability of carboxyhemoglobin to inhibit tetramer accumulation. A Western blot analysis of naturally formed globin-spectrin conjugates demonstrated irreducible complexes of globin with both bands 1 and 2. The complexes are tentatively designated "h1" and "h2". This analysis also demonstrated that h1 is completely extractable from cell ghosts, whereas h2 is only 50% extractable. These findings are incorporated into a hypothesis linking globin-spectrin complexation and the consequent inhibition of spectrin dimer self-association to the clustered band 3 senescence antigen (Low et al, Science 227:531, 1985). PMID- 7795247 TI - Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood. AB - TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13. In some cases, both TEL alleles are affected, resulting in loss of wild-type TEL function in the leukemic cells. In addition, 5% of children with acute lymphoblastic leukemia (ALL) have 12p12-p13 deletions, suggesting that a tumor suppressor gene resides on 12p. These observations led us to consider whether TEL loss of function may contribute to the pathogenesis of ALL. In this report we show that the TEL gene maps between the polymorphic markers D12S89 and D12S98, and we use these flanking markers to screen paired diagnosis and remission samples from 81 children with ALL for loss of heterozygosity (LOH) at the TEL gene locus. Fifteen percent of informative patients showed TEL LOH which was not evident on cytogenetic analysis. Detailed examination of patients with LOH at this locus showed that the critically deleted region included two candidate tumor suppressor genes: TEL and KIP1, the gene encoding the cyclin dependent kinase inhibitor p27. These studies show that LOH at the TEL locus is a frequent finding in childhood ALL. PMID- 7795246 TI - Collection and transplantation of peripheral blood stem cells in very small children weighting 20 kg or less. AB - The safety and efficacy of harvesting peripheral blood hematopoietic stem cells (PBSC) were evaluated in 38 children weighing 20 kg or less, with the smallest patient weighing 7 kg. The patients had a median age of 42 months and included 26 children with acute leukemias or lymphoma and 12 with various solid tumors. A total of 81 aphereses were performed, mostly in the recovery phase of chemotherapy, with or without granulocyte colony-stimulating factor, using a CS 3000 cell separator and regular procedure no. 3. Blood was withdrawn at a mean rate of 30 mL/min (range, 17 to 46 mL/min) through a temporary radial arterial catheter (20 to 24 guage) and returned through a larger catheter in a peripheral vein. Morbidity related to PBSC harvest was low and all aphereses were completed within 3 hours. The volume of blood per kilogram processed for each apheresis ranged from 85 to 615 mL (median, 270 mL). The median number of colony-forming units--granulocyte-macrophage (CFU-GM) and CD34+ cells collected were, respectively, 34 x 10(4)/kg and 15 x 10(6)/kg per apheresis and 126 x 10(4)/kg and 31 x 10(6)/kg per patient. Thirty-three patients (87%) required only a single apheresis to collect the minimum requirement of 10 x 10(4) CFU-GM/kg, including 28 patients (74%) from whom 30 x 10(4) CFU-GM/kg was obtained in a single apheresis. Twenty-three of the patients subsequently underwent autografts with PBSC. The median number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were, respectively, 10 (range, 6 to 15) and 14 (range, 9 to 46). The patients remained dependent on platelet transfusion support for a median of 10 days (range, 5 to 35). Thus, harvesting PBSC in very small children with active cancers is effective and safe and does not involve the risk of anesthesia or multiple invasive marrow aspirations. PMID- 7795248 TI - Human/mouse radiation chimera are capable of mounting a human primary humoral response. AB - Lubin et al recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated normal strains of mice, radioprotected with bone marrow (BM) from donors with severe combined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antigen, such as tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg), as well as a significant primary response to keyhole limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera was attained 2 to 4 weeks after the immunization and declined thereafter. One week after transplantation, the predominant anti-KLH subtype was IgM, while after 2 weeks, the dominance had shifted to IgG. Similar primary antibody response was also demonstrated against the human immunodeficiency virus (HIV) Nef protein. Comparison between human/Balb and human/SCID chimera showed a major difference in their ability to mount a primary response against KLH. In Balb/c recipients, more than half of the mice exhibited marked IgM titers against KLH, while there was hardly any anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chimera, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells. PMID- 7795250 TI - Neurologic complications after bone marrow transplantation for sickle cell anemia. PMID- 7795249 TI - Bicentric origin of sickle hemoglobin among the inhabitants of Mauritius Island. PMID- 7795251 TI - Wider benefits of leukodepletion of blood products. PMID- 7795252 TI - Parvovirus B19 induced red blood cell aplasia in a patient with hereditary pyropoikilocytosis. PMID- 7795253 TI - Recombination activating gene-expression in lymphoma cell lines and lymphomas. PMID- 7795254 TI - Pulse cyclophosphamide to treat idiopathic thrombocytopenic purpura. PMID- 7795256 TI - Recombinant human megakaryocyte growth and development factor stimulates thrombocytopoiesis in normal nonhuman primates. AB - Megakaryocyte growth and development factor (MGDF) is a novel cytokine that binds to the c-mpl receptor and stimulates megakaryocyte development in vitro and in vivo. This report describes the ability of recombinant human (r-Hu) MGDF to affect megakaryocytopoiesis in normal nonhuman primates. r-HuMGDF was administered subcutaneously to normal, male rhesus monkeys once per day for 10 consecutive days at dosages of 2.5, 25, or 250 micrograms/kg of body weight. Bone marrow and peripheral blood were assayed for clonogenic activity and peripheral blood counts were monitored. Circulating platelet counts increased significantly (P < .05) for all doses within 6 days of r-HuMGDF administration and reached maximal levels between day 12 and day 14 postcytokine administration. The 2.5, 25.0, and 250.0 micrograms/kg/d doses elicited peak mean platelet counts that were 592%, 670%, and 449% of baseline, respectively. Bone marrow-derived clonogenic data showed significant increases in the concentration of megakaryocyte (MEG)-colony-forming unit (CFU) and granulocyte-erythroid macrophage-megakaryocyte (GEMM)-CFU, whereas that of granulocyte-macrophage (GM) CFU and burst-forming unit-erythroid (BFU-e) remained unchanged during the administration of r-HuMGDF. These data show that r-HuMGDF is a potent stimulator of thrombocytopoiesis in the normal nonhuman primate. PMID- 7795255 TI - BCL-6 protein is expressed in germinal-center B cells. AB - Structural alterations of the 5' noncoding region of the BCL-6 gene have been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 10% of follicular lymphomas (FL), suggesting that deregulated BCL-6 expression may play a role in lymphomagenesis. Nucleotide sequencing of BCL-6 cDNA predicted a protein containing six zinc-finger domains, suggesting that it may function as a transcription factor. Using antisera raised against N- and C-terminal BCL-6 synthetic oligopeptides in immunoprecipitation, immunoblot, and immunocytochemical assays, this study identifies the BCL-6 gene product as a 95 kD nuclear protein. Western blot analysis of human tumor cell lines representative of various hematopoietic lineages/stages of differentiation showed that the BCL-6 protein is predominantly expressed in the B-cell lineage where it was found in mature B cells. Immunohistochemical analysis of normal human lymphoid tissues indicated that BCL-6 expression is topographically restricted to germinal centers including all centroblasts and centrocytes. The BCL-6 protein was also detectable in inter- and intra-follicular CD4+ T cells, but not in other follicular components including mantle-zone B cells, plasma cells, dendritic cells, and macrophages. Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements. These results indicate that the expression of the BCL-6 gene is specifically regulated during B-cell differentiation and suggest a role for BCL-6 in germinal center development or function. Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation. PMID- 7795257 TI - Granulocyte-macrophage colony-stimulating factor is not responsible for the correction of hematopoietic deficiencies in the maturing op/op mouse. AB - Osteopetrotic (op/op) mice are characterized by an autosomal recessive inactivating mutation resulting in the absence of biologically active colony stimulating factor-1 (CSF-1). Consequently, young op/op mice have a severe deficiency of macrophages and osteoclasts resulting in excessive bone formation, occlusion of the marrow cavity, and reduced marrow hematopoietic activity. Recently, we showed that the osteopetrosis and hematopoietic deficiencies evident in young op/op mice are not permanent but are progressively corrected with age. There are increases in osteoclast activity; bone resorption; femoral marrow space; and marrow hematopoietic activity, cellularity, and macrophage content. In the present study we show that CSF-1-/- granulocyte-macrophage colony-stimulating factor (GM-CSF)(-/-)-deficient mice also undergo the same pattern of hematopoietic correction as the op/op mouse. Also, like the op/op mouse, the peritoneal cellularity and macrophage content of CSF-1/GM-CSF-deficient mice remains severely reduced. Our data show that the "knockout" of GM-CSF does not change the op/op phenotype, and that GM-CSF is not essential for the correction of the hematopoietic deficiencies in the op/op mouse. Importantly, the data also show that neither GM-CSF nor CSF-1 is an absolute requirement for the commitment of primitive hematopoietic stem cells to the macrophage lineage or for the differentiation of at least some classes of macrophages. This finding suggests that an alternate regulatory factor can be involved in macrophage and osteoclast commitment, differentiation, and function in vivo. PMID- 7795259 TI - Computer games as a means of movement rehabilitation. AB - In order to improve arm control in a child with Erb's palsy, a computer game was used in which participation required the movement of a lever, controlled by the child's arm. Counter-balancing weights were used to facilitate movement but counteract pathological compensatory movements. The use of this system (with appropriate modifications at successive stages of therapy) produced a substantial improvement in arm control. It was concluded that the use of such techniques capitalizes on the child's motivation to succeed, and has advantages over traditional physiotherapy that relies on passive, repetitive movements and sometimes painful limb manipulation. In this situation the child made spontaneous, voluntary movements, concentrating on the outcome of movements rather than the actions per se. PMID- 7795258 TI - Human interleukin-3 receptor modulates bcl-2 mRNA and protein levels through protein kinase C in TF-1 cells. AB - Upon withdrawal of interleukin-3 (IL-3) from human factor-dependent erythroleukemic cell line TF-1, bcl-2 mRNA and protein levels decrease within 8 to 24 hours. Accompanying this decrease is the onset of apoptosis as determined by flow cytometric analysis of DNA degradation. By 8 to 18 hours of deprivation approximately 70% to 80% of the cells have entered apoptosis. Downregulation of protein kinase (PK) by a 24-hour incubation in 100 nmol/L 12-O-tetradecanoyl phorbol-13-acetate (TPA) in the presence of IL-3 dramatically reduced bcl-2 mRNA levels, and induced apoptosis in the presence of IL-3. We have also found that even in the presence of IL-3, two inhibitors of PKC, light-activated calphostin and H-7, substantially reduced the levels of bcl-2 mRNA between 8 and 24 hours as measured by a semi-quantitative reverse transcriptase/polymerase chain reaction assay method; however, the cyclic nucleotide-dependent PK inhibitor HA 1004, that is a structural analog of H-7 but a poor inhibitor of PKC, did not reduce bcl-2 levels in the presence of IL-3. This decrease in bcl-2 mRNA was accompanied by a decline in bcl-2 protein levels by 8 to 24 hours after addition of light activated calphostin. In addition to interfering with the maintenance of bcl-2 mRNA levels, inhibition of PKC with H-7 inhibited the induction of bcl-2 mRNA in factor-deprived TF-1 cells restimulated with IL-3. The cyclic nucleotide dependent PK inhibitor HA 1004 did not inhibit IL-3-induced bcl-2 mRNA. Studies with actinomycin D showed that transcription plays a major role in maintaining bcl-2 levels in TF-1 cells, and it is therefore likely that IL-3 plays a role in maintaining bcl-2 transcription through activation of PKC in these cells. PMID- 7795261 TI - Lifestyle activities of the elderly: composition and determinants. AB - Recent work suggests that lifestyle can be considered using a 2 x 2 model of indoor/outdoor and work/leisure activities. This paper replicates the factor analysis of the Frenchay Activities Index (FAI) reported by Bond et al., using a group of subjects living independently in the community. Results confirmed empirically the existence of the four hypothesized dimensions of lifestyle. Further analyses demonstrated the construct validity of these dimensions by establishing their sensitivity to age, sex, domestic circumstances, and physical and cognitive status. We discuss ways in which various deficiencies in the FAI might be rectified in a revised index of activities designed to retain and clarify the four established dimensions of lifestyle. Future directions include the development of such an instrument, and its application as a rehabilitation outcome measure. PMID- 7795262 TI - Disability in late adolescence. II: Follow-up of perceived limitation. AB - The disabilities experienced by a large cohort of 18-year-olds have been reported in the previous paper of this series. In this paper, we present the results of a detailed examination of the extent to which the disabilities caused limitation in the everyday activities of this group of young people. The results showed that nearly three-quarters of the members of the sample reported having one or more difficulties in performing activities in their daily lives, though the extent of limitation on their activities was low for most adolescents. Of this group who reported any type of disablement, 23% indicated it imposed very little general limitation on their lives (on a five point scale) and 6% rated it at the highest degree of limitation. Approximately half those with a disability felt the condition was improving, but 28% required an aid or help from another person. From 8% to 11% of those with a disability rated it as serious in relation to aspects of their daily living (education, leisure, social and work) and about half of those with a serious degree of limitation had sought help. The most common disabilities related to behaviour, communication and situations, for example environmental factors. As part of an ongoing study, the results provide a base from which to examine the extent and severity of disability among young people and change in disability as a result of the ageing process. PMID- 7795260 TI - The genesis of handicap: definition, models of disablement, and role of external factors. AB - Handicap has proved to be the most contentious and arguably most misunderstood concept of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH). This paper reviews the definition and characteristics of handicap as presented in the original introduction to the ICIDH, and presents some of the alternative suggested definitions. Limitations in the way the original conceptual model for the consequences of disease was depicted have led to the development of alternative models which draw attention to the importance of external factors, particularly for the genesis of handicap. The nature of these external factors and the implications of alternative models for the testing of the conceptual framework are discussed. The expression of handicap as a product of an interaction of a person with impairment and disability and the environment draws attention to the options available for the decrease of handicap through the modification of the environment, and not only by attempting to ameliorate the impairment or disability. PMID- 7795263 TI - A perspective on occupational concerns of rehabilitation service providers. AB - While the roles, functions and personality characteristics of rehabilitation service providers have been widely researched, much less is known about the correlates and consequences of occupational stress in these groups. In the present study measures of occupational stress, job tension, job satisfaction, life satisfaction, and affective well-being were completed by 52 rehabilitation service providers drawn from a range of agencies in New Zealand. Respondents also completed two open-ended questions assessing significant stresses in their work and strategies whereby stress could be reduced. There were consistently high negative correlations between job stress and job satisfaction. The correlations of job tension with overall life satisfaction and affect were generally significant. Surprisingly there was no significant relationship between job satisfaction and general life satisfaction. There were some significant associations between job satisfaction and ratings of affect, but the pattern of results was inconsistent. Open-ended stresses identified by subjects included time pressure/workload problems, interpersonal issues, agency-created problems, and problems keeping up with the implications, for rehabilitation, of rapidly changing Government policy. Strategies for stress reduction that were identified involved more resources, training and skills; intra-agency reorganization and more effective management and communication; more networking with other professionals; and more stable, realistic and caring Government policy. Limitations of the study and future research directions were identified. PMID- 7795264 TI - Assessment of disability and handicap associated with dyspnoea in elderly subjects. AB - In a sample of 2792 community dwellers, aged 65 and over, randomly selected in an administrative area of southwestern France, eight items of the functional assessment scales had an independent association with dyspnoea, adjusting for age, visual or hearing impairments, depressive symptomatology, and cognitive impairment. These eight items included: two activities of daily living (dressing and continence), two instrumental activities of daily living (shopping and use of transportation), three Rosow items (walking half a mile, climbing stairs, and doing heavy housework), and a mobility scale. Disability increased with breathlessness grade in each of these items, but with different patterns, suggesting a hierarchical relationship between some Rosow, IADL and ADL items for the association of dyspnoea with disability. PMID- 7795265 TI - Stroke outcome in elderly people living alone. AB - We prospectively followed 178 elderly people living alone prior to stroke who survived at least 30 days. At the time of hospital discharge and at months 2, 6 and 12 post-stroke one-third of survivors were living alone and half were living at home, either alone or with another person. Seventy-five per cent of survivors discharged to live alone were still living alone 6 months after stroke. Subjects discharged to live alone did not differ from other subjects with respect to age, gender or pre-stroke Barthel ADL score. The group discharged to live alone had less severe stroke deficits and higher ADL scores 1 week after stroke. This difference in ADL scores was maintained at hospital discharge and maximal recovery. Eleven variables were significant univariate predictors of discharge home to live alone. In multivariate models the strongest predictors of discharge home to live alone were high Barthel ADL score at day 7, high Mini-Mental State Score, high leg power and absence of homonymous hemianopia. PMID- 7795266 TI - Cross-sectional assessment and subgroup comparison of functional disability in patients with rheumatoid arthritis in a Swedish health-care district. AB - A cross-sectional study was undertaken on 222 patients with rheumatoid arthritis (RA) within a Swedish health-care district. An exploratory analysis of functional status, according to a Swedish version of the Health Assessment Questionnaire (HAQ), was carried out in order to explore the extent and pattern of functional disability in an unselected group of individuals with RA. The mean score of functional disability according to HAQ increased with more clinical manifest disease. There were no significant differences between the mean score in men and women. Most functional disability was related to hand-grip function and the ability to take care of personal hygiene. Increased functional disability was significantly associated with increasing age and disease duration. There was no significant relation between functional status and housing condition and educational level. A strong correlation was found between pain and functional disability. Multiple regression analysis was performed and predictive functional scores were tabulated based upon sex, age at onset and duration of RA disease. PMID- 7795268 TI - Topoisomerases II alpha and beta as therapy targets in breast cancer. AB - Topoisomerase II enzymes play an essential role in human DNA metabolism. They are also recognized as primary targets of a number of anti-cancer drugs used in the treatment of breast cancer, which remains a leading cause of cancer-related death in women. While topoisomerase inhibitors have produced significant response rates in this disease, their use has been limited both by toxicity and by the development of resistance. In this article we review the extensive work which has not only increased our understanding of the biochemistry and molecular biology of type II topoisomerases but also enabled more rational drug design. Such knowledge should translate into increased clinical efficacy in the treatment of breast cancer and other malignancies. PMID- 7795269 TI - Multidrug resistance. AB - Since we found verapamil as a multidrug resistance (MDR) reversing agent in 1981, many MDR reversing compounds have been reported. This type of drug must have strong effects with little side effects. We recently found MS-209 and PSC-833 as reversing agents. These two compounds interacted directly with P-glycoprotein, and showed a good MDR reversing effect in vitro and in vivo. MRK16, an antibody against P-glycoprotein, also showed a good therapeutic effect against drug resistant human tumors. MS-209, PSC-833 and the antibody against P-glycoprotein are interesting candidates for clinical use in the future. PMID- 7795267 TI - Design of synthetic branched-chain polypeptides as carriers for bioactive molecules. AB - New groups of synthetic biodegradable branched chain polypeptides have been prepared with the general formula poly[Lys-(Xi-DL-Alam)] or poly[Lys-(DL-Alam Xi)] [AXK], where m approximately 3 and i < 1, and used to elucidate structural and functional properties required for the selection of macromolecular carriers for (i) targeting/delivery of antitumor agents (e.g. daunomycin, methotrexate, boron derivatives), peptide hormones (e.g. GnRH antagonist) or radionuclides for imaging (e.g. 123I, 111In, 51Cr) or therapy (e.g. 153Sm, 131I) or (ii) the construction of synthetic antigens with peptide epitopes of mucin or Herpes Simplex virus glycoprotein D. Principles applicable for a rational carrier design are outlined based on chemical (size, charge, solution conformation) and biological (cytotoxicity, pirogenicity, biodegradation, immunogenicity, immunomodulatory potential, biodistribution) characterization of these biopolymers and their conjugates. PMID- 7795271 TI - Intensive consolidation chemotherapy for newly diagnosed acute myeloid leukemia using a regime containing moderate dose cytosine arabinoside and mitoxantrone. AB - Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy. PMID- 7795270 TI - A randomized trial of two schedules of trimetrexate versus 5-fluorouracil in advanced colorectal cancer: a Southwest Oncology Group study. AB - Trimetrexate (TMQ), a non-classical folate antagonist, was studied in a randomized controlled trial in patients with advanced colorectal cancer and without prior chemotherapy. Patients were randomly assigned to one of three treatments: TMQ at 200 mg/m2 i.v. q 2 weeks, TMQ at 12 mg/m2 i.v. daily x 5 or 5 fluorouracil (5-FU) at 15 mg/kg i.v. weekly. Overall response rates were: 6% (four partial responses in 71 patients, 95% CI of 2-14%) for q 2 week TMQ, 0% (zero of 29, 95% CI of 0-29%) for daily x 5 TMQ and 18% (two complete and nine partial responses in 62 patients, 95% CI of 9-30%) for 5-FU. Median survival estimates were 10.3 months for the q 2 week TMQ schedule, 8.7 months for the daily x 5 TMQ schedule and 13.6 months for the 5-FU schedule. Grade < or = 3 toxicities were significantly more common with TMQ. TMQ does not appear to have significant antitumor activity against colorectal cancer. PMID- 7795272 TI - Deoxyspergualin: phase I clinical, immunologic and pharmacokinetic study. AB - Deoxyspergualin (DSG) is an analog of the polyamine spergualin with preclinical evidence of activity in murine and human tumor models. This phase I study examined a 120 h continuous infusion schedule in 56 patients with refractory solid tumors at doses ranging from 80 to 2792 mg/m2/day. Dose-limiting toxicity was reversible hypotension and appeared to be associated with plasma levels of DSG > 4 micrograms/ml. Other dose-dependent effects noted were pruritus and circumoral paresthesias. Myelosuppression and gastrointestinal toxicities were mild and sporadic. Two patients with refractory head and neck cancer had minor responses. The recommended phase II dose on this schedule is 1800 mg/m2. Additional monitoring to identify immunologic properties included immunophenotyping of peripheral lymphocytes and cytotoxic activity by means of standard 51Cr-release assays. These studies revealed a non-dose-dependent increase in the number of cells expressing T cell antigens predominantly the T suppressor (CD8) phenotype posttreatment. In three patients, a mild increase in LAK activity was noted post-treatment without a consistent relationship to dose or change in cell surface antigens. Pharmacokinetic studies were completed on 26 patients ranging from doses of 80 to 2792 mg/m2. The average plasma concentration ranged from 0.07 to 7 micrograms/ml. DSG was rapidly cleared from the plasma with a mean terminal half-life of 1.9 h. Mean total body clearance was 25.24 l/h/m2. Further in vivo immunologic studies should be pursued while the agent is studied in fixed dosage phase II clinical trials. PMID- 7795273 TI - Cost effectiveness of 5-hydroxytryptamine3 receptor antagonists: a retrospective comparison of ondansetron and granisetron. AB - As clinical and economic analyses to date have shown clear benefits of using the new 5-hydroxytryptamine3 receptor antagonists (5-HT3RAs) over traditional antiemetics, the choice between them may necessitate the assessment of comparative cost-effectiveness. This paper presents the results of an assessment of the relative cost-effectiveness of two current 5-HT3RAs: ondansetron and granisetron. The analysis was based on a retrospective assessment of the cost and effectiveness (defined as no vomiting and no worse than mild nausea) of these new antiemetics. Efficacy data were based on the results of two recently published directly comparative clinical studies of ondansetron versus granisetron in the treatment of chemotherapy-induced emesis following both single-dose and fractionated chemotherapy. The cost of treatment was derived by combining clinical data from these studies with manufacturers' drug prices, and published costs of drug administration and emetic episodes. Costs for inpatient stay and side-effects were assumed to be equal across both treatment alternatives. The results were expressed in terms of the total cost per patient of emetic treatment and the cost per well-controlled patient. On this basis, granisetron was found to be more than 50% more cost-effective than ondansetron. This result was robust to variation in key assumptions concerning efficacy and cost, although ondansetron would become the more cost-effective if the dose was reduced to one 8 mg i.v., with no concomitant loss of efficacy. PMID- 7795275 TI - In vitro assessment of Taxol for human glioblastoma: chemosensitivity and cellular locomotion. AB - Although the antineoplastic efficacy of Taxol against a variety of tumors has been established, it has only recently been used for malignant brain tumors. We evaluated in vitro chemosensitivity of glioblastoma to Taxol and the affect of Taxol on glioblastoma cell locomotion. The clonogenic assay was used to evaluate the chemosensitivity of five human glioblastomas and the C6 rat glioma. Cells exposed to Taxol (0-250 nM) were suspended in agar in capillary tubes. Following incubation, colonies were counted to determine percent survival. All six cell lines demonstrated sensitivity to Taxol (LD50 1 nM to > 250 nM). However, even at concentrations exceeding those achievable clinically, all cell lines had surviving cells, indicating a saturation threshold for Taxol cytotoxicity. Cell locomotion was evaluated using the radial dish assay to determine the rate of egress of cells from a region of high cell density to the periphery. Increasing Taxol concentration caused increased locomotion in all six cell lines (p < 0.0001). Although Taxol has significant cytocidal impact, it increases in vitro locomotion of glioblastoma cells. These findings suggest that the clinical use of Taxol for glioblastoma may slow the growth of bulk disease, but may also lead to increased tumor invasion. PMID- 7795274 TI - Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo. AB - RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions ranges from 3.5 in a human bronchio-alveolar tumor cell line up to 120 in a rodent cell line defective in the repair of DNA strand breaks. The ability of RB 90740 to cause DNA strand breaks under hypoxic conditions was confirmed by alkaline sucrose gradient and pulsed field gel electrophoresis techniques. Despite these properties demonstrated in vitro, RB 90740 was shown not to be cytotoxic to hypoxic cells in experimental murine tumors in vivo. This may be due, in part, to the level of hypoxia (< 0.02% O2) necessary to produce toxicity in vitro. PMID- 7795276 TI - Schedule-dependent enhancement of antitumor activity of ethyldeshydroxy sparsomycin in combination with classical antineoplastic agents. AB - The efficacy of the protein synthesis inhibitor ethyldeshydroxy-sparsomycin (EDSM) as a biochemical response modifier of several antitumor agents against L1210 leukemia and B16 melanoma is described. Seven drugs with different intracellular targets were selected for this combination study. Tumor implantation and drug treatment were both i.p., and the time interval between the administration of EDSM and the cytostatic agent was varied. Our results show that in the B16 tumor model EDSM is not able to potentiate any of these drugs, whereas antagonism is seen in combination with doxo-rubicin (DX). In the L1210 tumor model, however, no loss of activity is seen for this specific combination. The effect of the combination of cytosar (Ara-C), 5-fluorouracil (5-FU) or vincristine (VCR) with EDSM in the L1210 model is strongly time interval dependent. Loss of 5-FU antitumor activity is seen when EDSM is given 3 or 24 h after 5-FU; however, no effect is observed when EDSM is given 6 h after 5-FU. Enhancement of the 5-FU activity is not noticed. The VCR activity is potentiated when EDSM is given at least 6 h after VCR administration, which increases the antitumor response from 32 to > 60 days and the percentage survivors from 33 to 83% (p = 0.04). In combination with Ara-C, potentiation of antitumor activity is seen only when EDSM is given 24 h after Ara-C, which increases the antitumor response from 32 to > 55 days and the percentage survivors from 11 to 50% (p = 0.008). No modulatory effects are found when EDSM is combined with carmustine or DX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795277 TI - Selection of three out of 24 anti-cancer agents in poorly-differentiated gastric cancer cell lines, evaluated by the AUC/delta IC50 ratio. AB - The purpose of this study was to screen 24 anti-cancer drugs, either in use or in clinical study, using four cell lines, all of which originated from poorly differentiated gastric cancers. The MTT assay was used at 1, 6, 24 or 72 h exposure times as the chemosensitivity test. We also examined P-glycoprotein expression, mdr-1 gene amplification and the modifier effect of verapamil. All four cell lines generally showed the same chemosensitivity pattern, while GCIY cells showed mdr-1 gene amplification and P-glycoprotein expression, and KATOIII cells showed the multidrug resistant pattern without P-glycoprotein expression. Both cell lines acquired higher chemosensitivity after verapamil addition. All IC50 data (with or without verapamil) were multiplied by exposure time (delta IC50) and compared with the clinical 'area under the concentration curve (AUC)'. SN-38 with/without verapamil, cisplatin with verapamil and pirarubicin with/without verapamil seemed to be the best candidates for poorly-differentiated gastric cancer chemotherapy. Plant alkaloids could also be candidates. With further experiments, we may be able to deduce commonly effective chemotherapy for poorly-differentiated gastric cancer from these drugs. PMID- 7795278 TI - Cisplatin and carboplatin-mediated activation of murine peritoneal macrophages in vitro: production of interleukin-1 alpha and tumor necrosis factor-alpha. AB - Analysis of tissue culture supernatants collected from cisplatin (10 micrograms/ml) and carboplatin (50 micrograms/ml)-treated macrophages show enhanced activity of interleukin-1 alpha and tumor necrosis factor-alpha. Cytotoxicity of these supernatants was demonstrated using mouse sarcoma-180 cells. These results demonstrate the ability of cisplatin and carboplatin to enhance the immune system suggestive of yet another mechanism of their action in the regression of tumors. PMID- 7795279 TI - Efficacy of sulofenur and a second generation diarylsulfonylurea, N-[5-(2,3 dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), against colon adenocarcinoma xenografts. AB - Sulofenur and a second generation diarylsulfonylurea (DSU), N-[5-(2,3 dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), were evaluated against a panel of eight colon adenocarcinoma xenografts. Of these tumors, four were derived from adult patients and four from young patients (age range 11-26 years). Both drugs were administered twice daily by oral gavage, 5 days each week for two or three consecutive weeks. The maximum tolerated dose for sulofenur was 300 mg/kg/dose for three courses and 200 mg/kg/dose for LY295501. Against 'adult' derived tumors, sulofenur caused a high proportion of objective regressions of advanced xenografts in two of four lines, with significant inhibition of growth in three tumor lines. Colon adenocarcinomas from young patients were similarly sensitive to sulofenur with a high proportion of complete and partial responses in two of three lines. LY295501 demonstrated a very similar spectrum of activity against this panel of xenografts. Tumors intrinsically resistant to sulofenur were resistant to LY295501, although this agent was slightly more active than sulofenur against tumors from younger patients. In addition, xenografts were established from a cloned colon adenocarcinoma line (GC3/c1) and its derivative GC3/LYC5) selected in vitro for resistance to sulofenur. GC3/c1 xenografts were highly responsive to both sulofenur and LY295501, whereas GC3/LYC5 xenografts were completely resistant to both agents administered at the maximum tolerated dose and schedule. These results indicate that the second generation DSU, LY295501, demonstrates a similar spectrum of activity against colon tumors as does sulofenur, and that the mechanism of action and/or resistance to the two drugs is probably similar. PMID- 7795280 TI - Platin salts-induced hemolytic anemia: cisplatin- and the first case of carboplatin-induced hemolysis. AB - Anemia is a common side effect of cisplatin, especially after repeated infusions. The primary mechanisms is a myelosuppression caused by cisplatin's interference with iron metabolism, resulting in a lower count of red cell precursors. Some authors report a hemolytic anemia similar to penicillin-induced anemia, in which hemolysis is caused by an antiglobulin antibody directed against red cell membrane-bound cisplatin. The authors report two cases of cisplatin-induced anemia and suggest that the immune-complex hypothesis is responsible for hemolysis. The first case of carboplatin-induced hemolysis is also reported. Mechanisms of hemolysis and clinical practice are discussed. PMID- 7795281 TI - Re: "Liposome encapsulated vincristine: preclinical toxicologic and pharmacologic comparison with free vincristine and empty liposomes in mice, rats and dogs". PMID- 7795282 TI - Irritable bowel syndrome in children: an Italian multicentre study. Collaborating Centres. AB - A multicentre study was carried out on 285 children suffering from irritable bowel syndrome (IBS). Patients were divided according to clinical symptoms and age: Toddler's diarrhoea (TD) under 3 years of age and recurrent abdominal pain (RAP) over 3 years of age characteristics in children with TD and RAP were compared with those found in 114 subjects suffering from various gastrointestinal diseases (GIC) and in 192 normal children. This analysis allowed a complete profile of children with IBS in Italy to be obtained. The TD group, and to a lesser extent the RAP group, differ from the GIC and healthy controls (HC) on the basis of telephone calls to the doctor, physician visits, inappropriate dietary restrictions, multiple medications and multiple non-GI complaints. For children under 3, a history of food intolerance and the presence of mucus and undigested food in the feces are the variables that discriminate patients with IBS from those with GIC; for children over 3, colics in the first 3 months of life, a history of food intolerance, loose feces with abdominal pain, pain relieved by evacuation and undigested vegetables in the feces most discriminate the two groups. Finally, we tried to compute a diagnostic score to discriminate IBS children from GIC: this proved to be sensitive to IBS but not specific enough to be of clinical utility. PMID- 7795283 TI - Twelve-month omeprazole vs ranitidine in the treatment of Helicobacter pylori positive patients with healed duodenal ulcer. AB - We evaluated the results of a 12-month treatment using different regimens of omeprazole at the dose of 20 mg daily (three day week-end treatments and every other day) and of 150 mg nocte of ranitidine on Helicobacter pylori status and on preventing duodenal ulcer relapses in 140 Helicobacter pylori positive patients with healed duodenal ulcer. Only every-other-day omeprazole suppresses Helicobacter pylori after 3 month therapy (p < 0.001), after 6 months (p < 0.001) and 12 months (p < 0.05). After 3 months (T1) no significant effectiveness was found in the prevention of ulcer relapses by omeprazole and ranitidine. After 6 months (T2) a significant reduction of relapses (p < 0.05) was recorded when comparing every- other-day omeprazole to the weekend regimen. After 12 months every-other-day omeprazole treatment significantly reduced the relapses compared with the week-end therapy (p = 0.05) and with ranitidine (p < 0.05). PMID- 7795284 TI - Peptic ulcer and duodenal stenosis: role of Helicobacter pylori infection. AB - A 17-year-old boy who developed a symptomatic duodenal ulcer at 10 years of age with melena, and was then treated continuously for 6 years with ranitidine therapy that only partially controlled symptoms and peptic lesions, came to us with vomiting due to duodenal bulb stenosis and active ulcer. Four months of omeprazole (40 mg/die o.m.) did not modify the endoscopic picture. The diagnosis of H. pylori infection and its treatment with triple therapy led to the cure of both duodenal ulcer and bulbar stenosis. Afterwards he remained asymptomatic without any lesions or complications for 18 months. This case illustrates that H. pylori eradication: a) is able to cure refractory duodenal ulcer; b) resolves severe complications such as duodenal stenosis. PMID- 7795285 TI - Gastrointestinal complications of liver transplantation. AB - Liver transplantation (OLTx) has become a common procedure at many centers in Europe and North America. The 1 and 5 year survival of patients receiving liver transplants at most centers is 75-85% and 60-65% respectively. As such, many physicians, in addition to those at transplant centers, will be called upon to see and care for recipients surviving liver transplants. The gastrointestinal tract is a common site of post-transplantation problems. These problems involve all components of the gastrointestinal tract. Many have characteristic, if not unique, presentations and clinical courses. They are reviewed for the physician in clinical practice who does not practice at a transplant center. PMID- 7795286 TI - Clinical course of inflammatory bowel disease during treatment with interferon for associated chronic active hepatitis. AB - Seven patients with inactive ulcerative colitis and seven patients with Crohn's disease (5 inactive, 2 mildly active) received interferon treatment for associated chronic active hepatitis. Neither relapse (except in one patient) nor worsening of the clinical course of the inflammatory bowel disease was observed during treatment. According to these results chronic active hepatitis associated with inflammatory bowel disease can be treated with interferon without the risk of deteriorating the course of the inflammatory bowel disease. PMID- 7795287 TI - Monoethylglycinexylidide production and prediction of hepatic histology. PMID- 7795289 TI - Richard Wilhelm Gottlieb Faltin 1867-1952. PMID- 7795288 TI - Flow cytometry DNA content and morphobiological characteristics in chronic and neoplastic human liver disease. AB - In the search for parameters that can indicate changes in the behaviour of liver tissue from normal to chronic to neoplastic disease, DNA content by FCM (ploidy and percent of 4N cells) and morphobiological characteristics were investigated in fresh liver specimens of 16 patients with normal liver, 21 with persistent hepatitis (CPH), 23 with chronic active hepatitis (CAH), 17 with cirrhosis, and 13 with hepatocellular carcinoma (HCC). Aneuploidy was mostly found in HCC specimens (54%), whereas the percentage of 4N peak decreased in chronic hepatitis and cirrhosis patients but increased to 11.09% in HCC samples (r = -0.02; p = 0.05). Finally, the binuclearity rate decreased gradually from normal to flogistic to HCC specimens. The 4N peak and the binuclearity rate were closely correlated in non-HCC (p = 0.0006, by T-test) but not in HCC samples. Only DNA ploidy and the binuclearity rate have been confirmed as being significantly and independently related to the histology of liver tissue by multivariate regression analysis. PMID- 7795290 TI - Faciocraniosynostosis: from infancy to adulthood. PMID- 7795291 TI - The Goteborg protocol for treatment of craniosynostosis. PMID- 7795292 TI - Personal contributions to craniofacial surgery. PMID- 7795294 TI - Advances in craniofacial fracture repair. PMID- 7795293 TI - Vertical orbital dystopia: definition, classification and treatment. AB - Correction of vertical orbital dystopia is an important component part of providing facial symmetry in a number of conditions of varied etiology having facial imbalance and asymmetry. The most important step is the initial one of making a proper diagnosis, since some conditions represent globe dystopia rather than true orbital dystopia, and can be treated by extracranial procedures. However, if an intracranial procedure is felt indicated, it adds to the safety rather than the complexity of the procedure, and one should not hesitate advocating this to the patient. PMID- 7795295 TI - Craniofacial osteotomies and rigid fixation in the correction of post-traumatic craniofacial deformities. AB - Post-traumatic craniofacial deformities may result from failure to diagnose craniomaxillofacial injuries or from less than adequate repair. The skeletal deformities may be corrected by procedures employing extended craniofacial exposure, segmental osteotomies and bony repositioning. A graduated approach to the correction of regional bony post-traumatic deformities has been formulated. Bony depressions are corrected by onlay grafts, rigidly fixed with lag screws. Malposition of anatomically normal bone is corrected by osteotomy and repositioning. Anatomically abnormal bone is replaced with bone grafts. The use of rigid fixation techniques prevents the late skeletal relapse seen with previous techniques. In the established post-traumatic deformity, soft tissue distortion from contracted underlying scar tissue and adherence to bony depressions and defects is the limiting factor in restoring the pre-injury appearance. PMID- 7795296 TI - The names that we give to vitamins. PMID- 7795297 TI - How much can we learn from history? PMID- 7795298 TI - Occupation: teller of tales and physician. PMID- 7795299 TI - Scientists discover new element. PMID- 7795300 TI - Grass-roots of dependency. PMID- 7795301 TI - Public health in RI: a strategic allocation perspective. PMID- 7795302 TI - Technology and the cost of medical care. PMID- 7795303 TI - Preventive health attitudes and practices of elderly persons attending senior centers. PMID- 7795304 TI - Inpatient hospice care: a new option for the terminally ill. PMID- 7795305 TI - Lead poisoning among Rhode Island preschoolers. PMID- 7795306 TI - Lead poisoning among RI preschoolers: the cost. PMID- 7795308 TI - Effects of pronounced haemodilution on the plasma protein binding of lidocaine. AB - The effects of pronounced haemodilution on the protein binding of lidocaine was investigated in vitro in plasma from five healthy adult volunteers. The plasma was diluted with a phosphate buffer to reach a plasma protein concentration normally seen during paediatric cardiopulmonary bypass (CPB) and protein binding was determined at a low (1.5 micrograms/ml) and a moderate (4 micrograms/ml) total plasma concentration of lidocaine. The effects of different haematocrits on plasma protein binding was also determined over the haematocrit range 20-60%. The binding of lidocaine was found to be inversely related to the degree of dilution, i.e. the free fraction increased significantly with increasing dilution (p < 0.0001). Furthermore, the binding was dependent on the total plasma concentration of lidocaine, since a significantly higher percentage of free drug was found at the higher total lidocaine level (4 micrograms/ml) compared with the lower level (1.5 micrograms/ml) (p < 0.05). No significant difference in the free fraction of lidocaine could be found over the studied haematocrit range. The results of the present study indicate that plasma protein levels commonly associated with CPB in neonates and infants are associated with a significant increase in the free, unbound and pharmacologically active fraction of lidocaine compared with normal conditions. The use of commonly recommended dosages of lidocaine might result in toxic-free concentration in this setting. PMID- 7795307 TI - Factor XII deficiency and cardiopulmonary bypass. AB - Factor XII initiates the intrinsic coagulation cascade and may affect the fibrinolytic system. Routine coagulation tests used during cardiopulmonary bypass (CPB) are abnormal in factor-XII-deficient patients and are useless for monitoring anticoagulation in these patients. A factor-XII-deficient patient requiring CPB is described. The baseline celite activated clotting time (ACT) was greater than 1400 seconds and the thrombin time was 12.4 seconds (control, 11.9 seconds). Two units of plasma were given resulting in an ACT of 173 seconds. Following 300 units/kg of heparin and during CPB, the ACT ranged from 670-596 seconds with the thrombin time greater than 200 seconds. Plasma provides exogenous factor XII allowing an endpoint on the ACT test and may protect against possible postoperative hypofibrinolytic complications. A commercially available modified thrombin time may also be useful and provide an endpoint during high dose heparinization. PMID- 7795309 TI - The role of N-acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass. AB - The role of N-acetylcystein (NAC) administration on the oxidative response of neutrophils during cardiopulmonary bypass (CPB) was evaluated in a double-blind study. Twenty-four adult patients undergoing coronary artery bypass were included in the study. Twelve patients received NAC as a bolus of 100 mg/kg followed by a continuous infusion of 20 mg/kg/h in the bypass circuit from the beginning to the end of bypass. A further 12 patients received placebo. Citrated blood samples for measurement of oxidative burst response of neutrophils were obtained at different time points during bypass. The oxidative burst response of neutrophils in the patients receiving NAC was significantly low at all times during bypass. Based on these findings NAC appears to act as an oxygen free radical scavenger during open heart surgery. PMID- 7795310 TI - Cardiopulmonary bypass with adequate flow and perfusion pressures prevents endotoxaemia and pathologic cytokine production. AB - Endotoxin and cytokine inflammatory mediators comprise the afferent and efferent limbs of the 'acute phase response'. During cardiopulmonary bypass (CPB) there may be gut translocation of endotoxin and contact activation of lymphocytes. It has been hypothesized that the haemodynamic instability encountered following CPB is caused by the 'acute phase response'. In this study we attempted to quantify the acute phase response in patients undergoing open-heart surgery and determine the influence of these cytokines on perioperative morbidity. Four perioperative blood samples were drawn from 20 consecutive patients undergoing coronary artery bypass grafting (CABG). These samples were assayed for endotoxin and four cytokines. In all cases the cardiac index was maintained > 2.4 l/min/m2 during nonpulsatile normothermic bypass (37 degrees C) and > 1.8 l/min/m2 during nonpulsatile hypothermic bypass (28 degrees C), and the perfusion pressure > 60 mmHg. Endotoxin was not detected in any of the test samples despite positive nonpatient controls. Interleukin 6 (IL-6) and tumour necrosis factor (TNF) were not detected despite an assay sensitivity of 80 and 10 pg/ml, respectively. TNF was detectable with an assay sensitivity of 0.5 pg/ml although there were no significant differences within the group. Interleukin 1 (IL-1) was detected (range = 0.98 - 9.09 ng/ml) in patients and again there were no trends within the group. The platelet activating factor (PAF) values peaked at crossclamp release (1.3 ng/ml versus a baseline of 0.2 ng/ml); however, there was no significant difference within the study. PMID- 7795312 TI - The influence of vascular pressure and different primes on the fluid balance of, and oxygen supply to, the patient during CABG. AB - Detrimental changes of blood and erythrocyte rheology, and fluid exchange between the vascular and interstitial spaces, which influence the rate that oxygen is supplied to the patient, occur during cardiac bypass surgery. Venous flow is subject to a pulsatile and uncertain variation, because the vena cava is more than 30 mmHg below atmospheric pressure. This occurs because the patient is about 1 m above the air-blood surface of the bypass reservoir. Before any reliable study of fluid exchange can be undertaken this effect must be controlled. It was then established that optimum oxygen exchange occurs when equilibration of the plasma oncotic pressure and the capillary hydrostatic pressure is achieved without alteration of the interstitial fluid volume. At the lower arterial blood pressures used during bypass, it is necessary to reduce the plasma oncotic pressure by using an appropriate volume of crystalloid prime. PMID- 7795311 TI - Pulsatile compared with nonpulsatile perfusion using a centrifugal pump for cardiopulmonary bypass during coronary artery bypass grafting. Effects on systemic haemodynamics, oxygenation, and inflammatory response parameters. AB - The present study investigated the influence of pulsatile or nonpulsatile flow delivery with a centrifugal pump for cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG) in two randomized groups of 19 patients each. All patients received a standard anaesthetic and surgical protocol. Pulsatile perfusion during CPB was created by accelerating the baseline pump speed of the Sarns centrifugal pump at a rate of 50 cycles per minute. Measurements included perioperative systemic haemodynamics and oxygen exchange, total haemolytic complement (CH50), polymorphonuclear (neutrophil) granulocyte (PMN) count and plasma granulocyte elastase bound to alpha 1-proteinase inhibitor (E-alpha 1-PI). Laboratory measurements were corrected for haemodilution. During and after CPB there were only a few significant differences between the groups in systemic haemodynamics and oxygenation, i.e. a lower mean arterial blood pressure after the end of CPB in the nonpulsatile group (65 mmHg, SD = 11 vs 76 mmHg, SD = 11) and a lower SvO2 during rewarming on CPB in the nonpulsatile group (62%, SD = 8 vs 67%, SD = 8). The decrease in percentage of PMNs in the total white blood cell count during CPB was greater in the nonpulsatile group than in the pulsatile group (from 61 to 46% vs 63 to 53% of prebypass value). The steep increase of PMN count at the end of CPB and postoperatively was comparable in both groups. The maximal decrease of CH50 levels, occurring after surgery, was significantly higher in the nonpulsatile group (70% SD = 15 vs 79%, SD = 16, of baseline value), suggesting a greater complement activation. E-alpha 1-PI levels increased significantly in both groups during and after CPB with higher peak levels, obtained at one hour after admission to an intensive care unit, in the nonpulsatile group (316 micrograms/l, SD = 102) than in the pulsatile group (247 micrograms/l, SD = 106). There was a partly inverse correlation between the peak postoperative elastase levels and the PaO2/FiO2 ratios at the first postoperative morning. This ratio was significantly lower in the nonpulsatile group (211, SD = 56) than in the pulsatile group (247, SD = 62). Postoperative respiratory tract infection was more frequent in the nonpulsatile group (n = 9) than in the pulsatile group (n = 2). Adding a pulsatile component to centrifugal blood pumping during CPB may have benefits with regard to the possibly detrimental whole body inflammatory response to CPB. Further studies are warranted to investigate whether these differences will affect clinical outcome. PMID- 7795313 TI - Activation of the intracellular glutathione system by oxydative stress during cardiopulmonary bypass and myocardial perfusion. AB - The glutathione (GSH) system is the main defence of tissues against free radicals and red blood cells (RBC) are the most efficient sites for GSH redox cycle activation. Total GSH was assayed during cardiopulmonary bypass (CPB) in RBC and serum from the coronary sinus, peripheral arteries and veins in 18 children corrected of their cardiac defect. Our conclusions are: (1) RBC-GSH redox cycle is activated during heart ischaemia and reperfusion; (2) the activation of intracellular GSH system is preponderant compared with the extracellular one; (3) variations in intraerythrocytic total GSH during heart ischaemia and perfusion are detectable in peripheral veins and arteries, which can be the convenient sites for monitoring changes in the GSH cycle; and (4) increased total GSH levels are present in RBC before aortic crossclamping: at the beginning of mechanical ventilation in veins and, when CPB is started, also in arteries. PMID- 7795314 TI - Retrograde cerebral perfusion: overview, techniques and results. AB - Cardiovascular surgical repair of arch aneurysms is taking a step forward by going backwards by utilizing retrograde cerebral perfusion. Drs ME DeBakey, ES Crawford, DA Cooley and GC Morris first reported successful resection and repair of a fusiform aneurysm of the aortic arch with replacement graft in 1957. Since then, Crawford and Coselli have pursued materials and techniques which have made this procedure, one which generally resulted in high morbidity and mortality, more viable with decreased morbidity and mortality. Increased numbers of patients are now having this repair and are resuming normal healthy lives after the operation. From February 1992 to October 1993, 88 patients were surgically treated by Coselli who utilized retrograde cerebral perfusion with profound hypothermia and circulatory arrest, thus allowing for repairs that under any other conditions probably could not have been achieved successfully. It is evident that a major determinant for the successful clinical results, in addition to surgical technique and skill, was the employment of profound hypothermia and circulatory arrest. This article will review the techniques and results of aortic arch repair utilizing retrograde cerebral perfusion during circulatory arrest with profound hypothermia to lessen the chance of neurological morbidity following surgical replacement of the transverse aortic arch. PMID- 7795315 TI - A bivariate limiting distribution of tumor latency time. AB - The model of radiation carcinogenesis, proposed earlier by Klebanov, Rachev, and Yakovlev [8] substantiates the employment of limiting forms of the latent time distribution at high dose values. Such distributions arise within the random minima framework, the two-parameter Weibull distribution being a special case. This model, in its present form, does not allow for carcinogenesis at multiple sites. As shown in the present paper, a natural two-dimensional generalization of the model appears in the form of a Weibull-Marshall-Olkin distribution. Similarly, the study of a randomized version of the model based on the negative binomial minima scheme results in a bivariate Pareto-Marshall-Olkin distribution. In the latter case, an estimate for the rate of convergence to the limiting distribution is given. PMID- 7795316 TI - Deterministic models for the eradication of poliomyelitis: vaccination with the inactivated (IPV) and attenuated (OPV) polio virus vaccine. AB - Currently two polio vaccines, IPV and OPV, are in use which differ markedly in their epidemiological parameters. A simple epidemiological model in terms of ordinary differential equations is proposed to study the effects of vaccination campaigns using these vaccines. The numbers of interest are the reproduction number of the disease in the presence of vaccination and the critical vaccination coverage necessary to prevent an outbreak. For these numbers explicit representations are determined which can be used in comparing different vaccination strategies. PMID- 7795317 TI - On the simultaneous distribution of size and costs of an epidemic in a closed multigroup population. AB - A multitype stochastic epidemic model in which the infectivities and susceptibilities differ between subgroups is considered. To each infected are associated random effects of the infection, such as the development of a subsequent disease and the length of the infectivity period. Sums of the corresponding random variables are called costs of the epidemic. The asymptotic simultaneous distribution of the size and costs of large epidemics is derived. PMID- 7795318 TI - Phyllotaxis: the status of the field. AB - In the last decade important progress has been made regarding pattern recognition and generation of the phenomenon of phyllotaxis. Phyllotaxis, a central area in plant morphogenesis, proposes a challenge that reaches beyond the field of botany and whose resolution must be sought through evolutionary biology and general comparative morphology. This review summarizes the contributions in the area, redefines the challenge, and proposes an adequate framework for the study of the phenomenon. PMID- 7795319 TI - The effect of household distribution on transmission and control of highly infectious diseases. AB - Two epidemic threshold parameters are derived for the spread of a highly infectious disease in a community of households, where a household is any group whose members have frequent contacts with each other. It is assumed that the infection of any member of a household results in the infection of all susceptible members of that household. The threshold parameters have simple expressions in terms of the mean household size and the mean and variance of the number of susceptibles per household. They provide a basic reproduction number R0 for the spread of infection from individual to individual and a basic reproduction number RH0 for the spread of infection from household to household. The threshold parameters are used to derive the levels of immunity required for the prevention of major epidemics in the community. They are also used to evaluate various vaccination strategies having the same vaccination coverage. For a community with households of equal size, it is found that random vaccination of individuals is better than immunizing all members of a corresponding fraction of households. In contrast, when households have varying sizes, immunizing all members of large households can be better than a corresponding vaccination coverage of randomly selected individuals. It is illustrated that these threshold parameters can also be used for a community of households with schools or day care centers. In particular, the effectiveness of immunizing all members of a school is quantified. PMID- 7795320 TI - Prevention by chelating agents of metal-induced developmental toxicity. AB - Chelating agents such as calcium disodium ethylenediaminetetraacetate (EDTA), 2,3 dimercaptopropanol (BAL), or D-penicillamine (D-PA) have been widely used for the past 4 decades as antidotes for the treatment of acute and chronic metal poisoning. In recent years, meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3 dimercapto-1-propanesulfonate (DMPS) and sodium 4,5-dihydroxybenzene-1,3 disulfonate (Tiron) have also shown to be effective to prevent against toxicity induced by a number of heavy metals. The purpose of the present article was to review the protective activity of various chelating agents against the embryotoxic and teratogenic effects of well-known developmental toxicants (arsenic, cadmium, lead, mercury, uranium, and vanadium). DMSA and DMPS were found to be effective in alleviating arsenate- and arsenite-induced teratogenesis, whereas BAL afforded only some protection against arsenic-induced embryo/fetal toxicity. Also, DMSA, DMPS, and Tiopronin were effective in ameliorating methyl mercury-induced developmental toxicity. Although the embryotoxic and teratogenic effects of vanadate were significantly reduced by Tiron, no significant amelioration of uranium-induced embryotoxicity was observed after treatment with this chelator. PMID- 7795321 TI - Immune response of adult rats is altered by administration of diazepam in the first postnatal week. AB - The potential immunotoxic risk of perinatal treatment with diazepam was investigated using early postnatal administration of the drug to the rat and monitoring the immune response until the age of 24 months. Rats given a single dose of diazepam 10 mg/kg SC on the seventh postnatal day revealed at the age of 6 months a depression of cell-mediated immune response, and at the age of 12 months significant decrease of humoral immune response. The latter persisted until senescence (age 24 months). Also, a repeated dosage of diazepam (3 x 5 mg/kg/day SC on postnatal days 5 to 7) induced a significant depression of humoral immune response in 7-month-old rats. The results demonstrate that both the humoral and cell-mediated immune response of adult rats can be altered by administering diazepam in early postnatal life. PMID- 7795322 TI - Effect of a metallothionein antisense oligonucleotide on embryo development. AB - The effect of a metallothionein (MT) antisense oligodeoxynucleotide (ODN) on mouse preimplantation embryo development was investigated. Preimplantation embryos were cultured for 72 h and examined following exposure to either an MT antisense or sense ODN. Blastocyst formation (cavitation) and embryo cell number were lower in embryos exposed to the MT antisense ODN than in controls or in embryos exposed to the MT sense ODN. In embryos cultured in medium containing free nucleotides, cavitation frequency was not affected, although mean embryo cell number was lower than in controls. Combined, this work shows that an antisense ODN against MT can significantly affect blastocyst formation of preimplantation embryos; some, but not all, of the observed effects on embryo cell number may have been due to nucleotide toxicity. PMID- 7795323 TI - The use of cultured ovarian fragments to assess toxicant alterations in steroidogenesis in the Sprague-Dawley rat. AB - This study was conducted to determine the utility of using steroid production by cultured ovarian fragments to assess toxicant-induced alterations in ovarian steroidogenesis in Sprague-Dawley rats. To this end, serum steroid concentration and steroid production (progesterone (P4), testosterone (T), estradiol (E2)) by cultured ovarian fragments is described during a normal 4-day estrous cycle. This culture system was then used to profile the effects of aminoglutethimide shown to have two sites of steroidogenic inhibition, side chain cleavage enzyme and aromatase. LH, FSH, P4, and E2 concentrations in serum during the 4-day estrous cycle confirmed that described in the literature for untreated rats. All of the steroids measured had peak production levels during proestrus. The patterns of P4 and E2 production by the ovaries in an unstimulated culture mimics that seen in serum. Stimulation with hCG (100 mIU/mL) after the initial 1 h culture tends to even out the production of P4, while T production rises faster and peaks earlier. The pattern and levels of estradiol production in hCG-stimulated cultures are very similar to those in the unstimulated culture, both in pattern and in production levels. When cultured ovarian fragments from proestrous rats were treated in vitro with aminoglutethimide (1 to 16 microM), the pattern of steroid production that characterized the inhibitory effects were similar to those reported in the literature using isolated cell culture procedures. This pattern showed a rapid decrease in E2 production (IC50 of 2.43 microM), a concurrent rise in T production, and a decrease in P4 production (IC50 of 15.5 microM). This culture system is an appropriate system to rapidly assess toxicant effects on ovarian steroidogenesis following in vivo or in vitro exposure. PMID- 7795324 TI - Morphine induces reproductive changes in female rats and their male offspring. AB - The effect of intrauterine morphine exposure on the development of reproductive functions has been investigated in the rat. Female rats were treated daily ip with morphine sulfate, doses increasing at 10-d intervals from 5, 7.5, 10, to 15 mg/kg. These rats were mated between day 38 and 45, and morphine treatment continued at 20 and 30 mg/kg over pregnancy and at up to 40 mg/kg for 10 d postpartum. The treatment mainly disrupted ovarian cyclicity; only 48% exhibited normal cyclicity. Of these, 43% became pregnant when mature male rats were placed with them. Litter size was normal but with significantly more stillbirths in each litter and live pups had decreased body weights. Male offspring had reduced body weight at the time of weaning that persisted until 60 d of age. At 120 d, animals showed complete abolition of spermatogenesis and drastically reduced testicular steroidogenesis. Plasma LH levels were low, and hypothalamic noradrenaline was high. PMID- 7795325 TI - Effect of counseling on maternal reporting of adverse effects in nursing infants exposed to antibiotics through breast milk. AB - In a recent trial, we found that nursing women reported diarrhea in their nursing infants after maternal use of antibiotics. However, because they were told that this could occur during a medication counseling session, the observed effect could have been due to a reporting bias. The objectives of this study were to determine if counseling nursing women about side effects of antibiotic they used could (a) influence the adverse event reporting rate or (b) influence maternal nursing and medication compliance behavior. In a randomized, controlled trial, nursing women calling a teratogen information service for advice about selected antibiotics received one of two possible counseling formats (A and B). Both groups were informed that the antibiotics were safe to use. Mothers in group B were also informed about a theoretical risk of diarrhea in the infant. Mothers later reported clinical events they noted in the infants and judged whether they were due to the antibiotic. Eighty-seven percent (54/62) of group A subjects compared to 68% (52/76) of group B subjects reported clinical events in their infants during their antibiotic therapy (P = 0.017). The incidence of reported diarrhea was 26% in group A compared to 17% in group B (P = 0.3); 34% of subjects in both groups attributed clinical events to antibiotic therapy (P = 1.0). Diarrhea was attributed to antibiotic therapy in 13% of group A and 12% of group B subjects (P = 1.0). No differences were observed between groups in breastfeeding pattern and antibiotic compliance. Breastfeeding women counseled about adverse effects were not more likely to report side effects in their infants or to change nursing behavior and medication compliance. PMID- 7795326 TI - Teratogenic effects of DA-125, a new anthracycline anticancer agent, in rats. AB - DA-125 is a new anthracycline antitumor antibiotic derived from adriamycin. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin. The potential of DA-125 to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred twenty mated SD rats (sperm in vaginal lavage = day 0) were distributed among three treated groups and a control group. DA-125 was given at dose levels of 0, 0.1, 0.3, and 1.0 mg/kg/day administered intravenously to pregnant rats from days 7 to 17 of gestation. All dams were subjected to caesarean section on day 20 of gestation. At 1 mg/kg/day, reduced food intake, reduced body weight, and decreased spleen weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 11.9, 41.8, and 14.5%, respectively. Characteristic malformations included exencephaly, gastroschisis, cleft lip, dilatation of lateral and third ventricles, and fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3 mg/kg. The results show that DA-125 is teratogenic at a minimally maternally toxic dose in rats. PMID- 7795327 TI - Opioid peptides involvement in endotoxin-induced suppression of LH secretion in ovariectomized Holstein heifers. AB - Three groups of ovariectomized Holstein heifers were used in this study. Group I heifers (n = 6) were pretreated with saline (SAL), followed 3 h later by three injections of naloxone hydrochloride (NLX) given 1 h apart. In the same sequence, group II heifers (n = 3) received lipopolysaccharide (LPS), followed by the opioid antagonist NLX. Group III heifers (n = 3) received LPS followed by SAL. Concentrations of cortisol and progesterone increased (P < 0.05) following LPS injections in both groups II and III, whereas luteinizing hormone (LH) concentrations were suppressed (P < 0.05). Administration of NLX to heifers pretreated with LPS elicited significant increases (P < 0.05) in LH concentrations, whereas SAL infusion had no effect. These results indicate that the inhibitory actions of opiate mu-delta receptors, and possibly other POMC gene products, were at least partially involved in LPS-induced suppression of the gonadotropic hormone. These results are discussed, including the possibility that feedback suppression by LPS-triggered adrenal gland steroids may have interfered with complete restoration of LH secretion by the opioid antagonist. PMID- 7795328 TI - An assessment of lithium using the IEHR Evaluative Process for Assessing Human Developmental and Reproductive Toxicity of Agents. IEHR Expert Scientific Committee. PMID- 7795329 TI - The P blood group system: biochemical, serological, and clinical aspects. PMID- 7795330 TI - Centralized transfusion service: a novel approach to the delivery of transfusion services. AB - The development and expansion of the CTS in Pittsburgh shows the feasibility of this transfusion medicine delivery system. Few of the changes driven by health care reform both improve patient care and reduce costs. When properly implemented, a CTS achieves these objectives, benefits the community as a whole, and enhances the role of transfusion medicine specialists and the blood center in the region. PMID- 7795331 TI - Hemoglobin determination in blood donors. PMID- 7795332 TI - The mechanisms of leukocyte removal by filtration. PMID- 7795333 TI - The proficiency testing of platelet counting. AB - Ontario's laboratory professionals have shown that they are able to successfully operate a proficiency testing program by making use of volunteers. The program serves and assists the laboratory directors in their own quality assurance program. The two prime reasons for the success of LPTP are that it is not seen by the professions to be regulatory and that it emphasizes education, not punitive action. Whereas platelet performance below 100 x 10(9)/L is not as accurate as the remainder of the clinical range, most Ontario laboratories seem to perform platelet determinations at clinically acceptable levels. PMID- 7795334 TI - How safe is autologous donation before cardiac surgery? PMID- 7795335 TI - Applications of flow cytometry in transfusion medicine. PMID- 7795336 TI - AHNA certificate program in holistic nursing courses. ANHA certificate program in healing touch courses. PMID- 7795337 TI - Aromatherapy: the scents for survival. PMID- 7795338 TI - Role modelling "warm fuzzies" at work. PMID- 7795339 TI - The power of love. PMID- 7795340 TI - The Chernobyl accident and pregnancy outcome. PMID- 7795341 TI - Aminophylline versus caffeine citrate for apnea and bradycardia prophylaxis in premature neonates. AB - We investigated the efficacy and adverse effects of aminophylline and caffeine citrate in 180 premature neonates for 10 days and nights. Aminophylline (n = 98) and caffeine citrate (n = 82) were equally effective in preventing apnea and bradycardia. The caffeine citrate group had a lower median heart rate on day 3, fewer neonates with tachycardia and a smaller amount of gastric aspirate on day 7. The need for mononasal continuous positive airway pressure and respirator therapy was similar in both groups. We conclude that caffeine citrate is the drug of choice for apnea and bradycardia prophylaxis in premature neonates with a gestational age < or = 33 full weeks. PMID- 7795342 TI - Methaemoglobinaemia among neonates in a neonatal intensive care unit. AB - After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n = 33) of 415 neonates were found to be methb positive (defined as > or = 6% methb). Mean methb was 19% (range 6.5-45.5%). Maximum methb concentrations were found on day 4-31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25-30 weeks of gestation and 60% with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r = 0.38, p = 0.02). Measurements of C-reactive protein and leucocytes, NADH reductase, pH, Cl, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170 g and that of negative controls 1380 g (p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795343 TI - Cord blood cells and indices: smoking-related differences between the sexes. AB - The values of whole blood cell count, leucocyte differential, and platelet and reticulocyte counts were determined in cord blood of both male (n = 64) and female (n = 75) newborns of 87 non-smoking and 52 smoking mothers. Leucocytes and neutrophils in cord blood from the male newborns of smokers were significantly lower than those in their female counterparts and in male newborns of non smokers. These results suggest that male newborns are more affected by cigarette exposure than females with regard to some haematological parameters. PMID- 7795344 TI - Sleeping position and sudden infant death syndrome (SIDS): effect of an intervention programme to avoid prone sleeping. AB - The proportion of prone sleeping among sudden infant death syndrome (SIDS) victims and infants in general, and the rate of SIDS were prospectively studied in the county of Hordaland, Norway, three years before (1987-89) and three years after (1990-92) a campaign to discourage prone sleeping. Before the campaign, 64% of random reference infants were put prone versus 8% after (p < 0.0001). Concurrently, the rate of SIDS decreased from 3.5 to 1.6 per 1000 live births (63 infants before and 30 after the campaign, p = 0.0002). Prone sleeping was not considered a statistically significant risk factor for SIDS before (OR 2.0, 95% CI 0.8-4.5), but was highly significant (OR 11.3, 95% CI 3.6-36.5) after the campaign. Prone sleeping is an important risk factor for SIDS, but the association may be missed in epidemiological studies if prone is the predominant sleeping position. Behaviour with regard to sleeping position may be changed rapidly by means of a simple campaign. PMID- 7795345 TI - Arterial oxygen saturation in infants at risk of sudden death: influence of sleeping position. AB - To study the possible influence of sleeping position on arterial oxygen saturation, measured by pulse oximetry (SpO2), 7-h overnight recordings of breathing movements and ECG were performed in 43 infants (median age 2.4 months, range 0.2-11 months) at increased risk of sudden infant death syndrome (SIDS). Infants were randomly allocated to start sleeping either in their usual sleeping position or in the opposite position. After 3.5 h, all infants were gently turned over. Thus, each infant served as their own control. Recordings were analysed for sleep time, baseline SpO2 (only during regular breathing), and the number and duration of desaturations (a decrease in SpO2 to < or = 80%). In the prone position, a significantly higher proportion of time was spent asleep (median 79% versus 70%; p < 0.05). Median baseline SpO2 was 98.8% (91.7-100%) in the prone and 99.0% (92.0-100%) in the supine position (ns). A total of 191 desaturations were found in 29 recordings; 96 in the prone and 95 in the supine position (ns). One infant subsequently died of SIDS while sleeping in the prone position. He had a relatively high number of desaturations (n = 12) which all occurred in the prone position. These results confirm earlier studies which could not find a significant influence of sleeping position on baseline oxygenation. The occurrence of desaturations in the prone position only in the infant who subsequently died requires further investigation. PMID- 7795346 TI - Rate of radial bone mineral accretion in healthy children. AB - Radial bone width and mineral content were measured in 392 healthy Cambridge children aged 6-12 years from a cohort of 420 children studied 2 years previously. The typical rate of bone mineral accretion was 0.044 g/cm/year for boys across the whole age range and 0.042 g/cm/year for girls up to a mean age of 9 years, rising rapidly thereafter in association with changes in body size. The factors best predicting bone mineral accretion rate were mean bone mineral content, mean height, height velocity, weight velocity and bone width velocity. After adjusting for anthropometry, age did not contribute to the model. These are the first available longitudinal reference data for the rate of radial bone mineral accretion in healthy children. PMID- 7795347 TI - Dietary calcium, saturated fat, fiber and vitamin C as predictors of forearm cortical and trabecular bone mineral density in healthy children and adolescents. AB - Diet, weight-bearing physical activity (WPA) and daylight hours spent outdoors (DE) were related to bone mineral density in the distal (BMDd) and ultradistal (BMDud) forearm of 495 healthy children (8-11 years) and adolescents (11-17 years). BMD was assessed by single photon absorptiometry. Using multiple regression, BMDd was predicted by saturated fat and BMDud by fiber in children. In adolescents, BMDd was predicted by saturated fat and vitamin C, and BMDud by calcium and vitamin C. WPA and DE were not related to BMD. In conclusion, our results showed that current intake of calcium, saturated fat, fiber and vitamin C were positively associated with forearm BMD in children and adolescents. These associations depended on age and bone type. If our findings are verified, dietary recommendations, especially when aimed at young people, may have to be reconsidered. PMID- 7795348 TI - Does age at the start of breast feeding influence infantile diarrhoea morbidity? A case-control study in periurban Guinea-Bissau. AB - Colostrum protects the newborn from intestinal infection by its content of secretory immunoglobulin A and other immediately acting factors. It may also induce maturation of the child's gastrointestinal immune defences, thus contributing to the protection against diarrhoeal disease later in infancy. To test this hypothesis, a case-control study on breast feeding and diarrhoea was carried out in a periurban community in Guinea-Bissau. The child's age at the start of breast feeding was ascertained soon after birth (n = 279). Subsequent cases of acute diarrhoea (n = 66) were identified at 3-monthly examinations, and four concurrent controls were randomly selected among attendants. Three separate estimates of association showed that the cases tended to have started breast feeding later after birth than the diarrhoea-free controls, but no single test was statistically significant. Early breast feeding might have consequences for diarrhoeal morbidity after the neonatal period. PMID- 7795349 TI - Contact allergy in relation to hand eczema and atopic diseases in north Norwegian schoolchildren. AB - Patch testing was carried out in 424 schoolchildren (223M, 201F), aged 7-12 years, in northern Norway. In 99 (23.3%) of these children, one or more allergic patch test reactions were demonstrated; 30 children reacted to two and 6 to three or more substances; 53 irritant reactions were recorded in 33 (7.8%) of those tested. From a total of 144 positive tests, the most common allergen was nickel (14.9%), followed by cobalt (5.7%), kathon CG (5.2%), lanolin (1.7%) and neomycin (1.4%). Both allergic and irritant reactions were found twice as frequently in girls as in boys. Positive patch tests were significantly more frequent in atopic (28.8%) than in non-atopic (17.9%) children, being most pronounced in atopic girls (37.4%). Hand eczema was reported to have occurred or to be present in 6.5% of cases. Twenty-nine of 36 children reporting hand eczema participated in the clinical examination. Altogether 15 (3.5%) children had hand eczema at the time of the clinical examination but 12 of these children had no previous history of hand eczema. In 14 of these 15 subjects, the eczema was localized to the back of the hands, with 13 having atopic dermatitis. In 4 of these 15 children, an allergic patch test reaction was found; however, in only 2 of these 4 was the test considered to be clinically relevant for the diagnosis allergic hand eczema. In conclusion, irritant hand eczema may occur in early childhood and is most prevalent in children with atopic dermatitis. PMID- 7795350 TI - Factors triggering the first febrile seizure. AB - The symptomatology of infections as well as immunological and virological findings were analysed using a logistic model in a survey of 58 children experiencing their first febrile seizures. These were then compared with findings in 116 age- and sex-matched controls with infections but no seizures. There were no statistically significant differences in the aetiology of infections between patients and controls. High temperature was the only variable to explain the occurrence of febrile seizures in the logistic model after adjusting for duration of symptoms (partial correlation coefficient in logistic model, r = 0.31). The duration of symptoms before hospitalization was shorter in patients than in controls (mean 1.0 and 3.6 days). With a longer duration of symptoms, the likelihood of seizures diminished (r = -0.34). Patients in the seizure group had a significantly higher temperature at home than controls before hospitalization (39.4 versus 38.8 degrees C). Our findings of higher temperatures in children with febrile seizures supports its importance as the most important triggering factor in febrile convulsions. PMID- 7795351 TI - Neurological findings in early treated phenylketonuria. AB - Twenty early treated, normal intelligent patients (IQ: mean 101.4, SD 10.0; age: mean 10.11, SD 1.3 years) with classical phenylketonuria and 20 age-, sex- and IQ matched healthy controls were investigated for neurological outcome, especially with regard to fine motor ability using the motor performance task ("Motorische Leistungsserie"). No pathological findings were seen on clinical neurological examination. The patient group had significantly poorer results in a concentration task (Test-d-2) as well as in some subtests of the motor performance task. Patients had difficulties in tasks which needed speed and precision of arm-hand-finger movements. High serum phenylalanine concentrations were significantly correlated with these deficiencies in fine motor ability. Our data demonstrated mild neurological impairment even in early and relatively strictly treated patients with phenylketonuria. PMID- 7795352 TI - Outcome of pregnancy in women with myotonic dystrophy and analysis of CTG gene expansion. AB - Pregnancy outcome was investigated in 32 women with clinically obvious myotonic dystrophy. The results indicated that there are two groups of women, those whose children have the adult type of myotonic dystrophy and those whose children have the congenital type. The overall perinatal mortality was 14%. Polyhydramnios was an obvious sign of the congenital type. No subclinical gene carrier was found among the children. We conclude that prenatal diagnosis should be offered to women with myotonic dystrophy, particularly to those who have previously given birth to a child with the congenital type. PMID- 7795353 TI - Incidence of acute otitis media associated with group A and B respiratory syncytial virus infections. AB - The comparative association of respiratory syncytial virus group A and B infections with acute otitis media was determined by analysing the hospital records of children with community-acquired respiratory syncytial virus infection during three successive outbreaks from 1987 to 1992. Of 326 episodes analysed, 192 (59%) were caused by group A and 134 (41%) by group B infections. Acute otitis media was diagnosed in 101 (75%) children with group B infection, compared with 119 (62%) with group A infection (p = 0.01). Group A infections were more often associated with wheezing (71% versus 59% in group B; p = 0.02) and oxygen therapy in inpatients (48% versus 31%, respectively; p = 0.008). The higher incidence of acute otitis media associated with group B infections was observed both after adjustment for potential confounding variables and during each outbreak. PMID- 7795354 TI - Deep Candida infection in child liver transplant recipients: serological diagnosis and incidence. AB - Nineteen children who received 22 orthotopic liver grafts on 20 occasions were studied with regard to Candida infection. Serum samples were analysed to determine Candida, IgA, IgM and IgG antibodies and detect free C. albicans glucoprotein antigen. Five children (25%) had a confirmed deep C. albicans infection (DCI) during the first 2 weeks after transplantation. In all children with DCI, serology was positive, a median of 6 days (range 2-9 days) before Candida infection was verified by fungal culture, direct microscopy and/or autopsy. The positive predictive values for Candida IgG, IgM and IgA antibodies in children with DCI were 100%, 78% and 100%, respectively, and for free C. albicans antigen, 45%. Pathological titres of IgM and IgA antibodies against Candida before liver transplantation were present in three of four children who later developed a DCI and in no child without infection. In conclusion, regular screening by Candida serology is recommended both before and after liver transplantation. PMID- 7795355 TI - Assessment of an abbreviated odorant identification task for children: a rapid screening device for schools and clinics. AB - To validate the level of olfactory performance of children, we tested 825 volunteers, aged 4-17 years, with an abbreviated form of our pediatric odorant identification task. The test consisted of sniffing and identifying five odorants (baby powder, bubble gum, candy cane, licorice and peach). Mean olfactory scores increased as a function of age, reaching a plateau of about 94-95% correct at 8 years of age. In general, girls out-performed boys. Physicians require a test instrument such as the one we have devised to allow them to diagnose olfactory dysfunction in children. The present task is particularly applicable in screening large numbers of children in clinics or schools because it can be administered easily and rapidly. Adult subjects with olfactory dysfunction also performed poorly on this odorant identification task designed for children. Therefore, we expect that our odorant identification task will also detect children with severe olfactory dysfunction. PMID- 7795356 TI - Adverse drug reactions in a paediatric intensive care unit. AB - Adverse drug reactions (ADRs) were prospectively studied in critically ill infants and children. Seventy-six ADRs were reported in 63 patients out of a study group of 899 patients. The majority of the ADRs were mild (49), although 19 were of moderate severity and 8 were severe. Thirty-five ADRs required treatment or alteration in treatment. Midazolam, morphine, salbutamol, vecuronium, hydrocortisone and theophylline were the drugs most likely to cause an ADR. One third of the ADRs were due to drugs used outside their product licence. The majority of the ADRs were reported by nurses (36) and pharmacists (30). We believe that it is possible to prospectively study drug toxicity in critically ill infants and children. PMID- 7795357 TI - Pediatric ECMO for pulmonary support: experience from 12 cases. AB - Extracorporeal membrane oxygenation (ECMO), which can be described as treatment with a modified heart-lung machine over a prolonged period of time, is used to support patients with life-threatening but potentially reversible lung failure. ECMO by itself does not cure the patient but gives the lungs a chance to rest while awaiting spontaneous or therapeutic healing. The method is well documented in the neonatal age group. In the non-neonatal age group, however, experience is less extensive. This report of the initial result from our hospital with 12 non neonatal pediatric cases shows high survival and low morbidity. Nine of the 12 patients were able to be weaned from ECMO (75% survival) and 8 of these 9 patients were long-term survivors. Medium time on the ventilator after discontinuation of ECMO was 4 days. At follow-up, all long-term survivors had no signs of neurological or pulmonary sequelae. These encouraging results point to the fact that ECMO should be considered more often in cases of life-threatening but potentially reversible pulmonary failure. PMID- 7795358 TI - The child group used as a reference system when analysing frequency of morbidity in day-care centres. AB - Morbidity frequency was analysed among children attending six day-care centres in a suburb of Stockholm, Sweden. Absence due to illness was calculated annually for each child and correlated with each child's own group. Thus a child was classified as "often sick" or "mainly healthy" in relation to the other children in the child's own group, constituting a reference system. In almost every group a "sick third" was found, whose absence due to illness was twice that of the rest of the group. Children from families of lower social standing, those with a relatively large number of siblings and those living in poor social conditions were found to be among those most often reported as sick. In such families, smoking was more commonplace. These parents more often lived in a rented apartment than in a single detached owner house. Multiple linear regression analysis revealed that young mothers and children with several siblings had the strongest correlation with absence due to illness of the proband child. Increasing maternal age revealed improvement vis-a-vis all socioeconomic parameters investigated, reflecting an improvement in standing correlated to less sick children. PMID- 7795359 TI - Enteropathogenic Escherichia coli O111ab:H2 penetrates the small bowel epithelium in an infant with acute diarrhoea. PMID- 7795360 TI - Biological zero in laser Doppler perfusion measurements: studies in neonates. PMID- 7795362 TI - Prophylaxis of Candida infections in transplanted patients. PMID- 7795361 TI - Two cases suggesting a role for the L-arginine nitric oxide pathway in neonatal blood pressure regulation. AB - Endogenous nitric oxide produced from L-arginine is a potent vasodilator that may be involved in blood pressure regulation. A male infant with argininosuccinate lyase deficiency, who could not synthesize L-arginine, was hypertensive prior to L-arginine replacement. The infusion of L-arginine resulted in a decrease in blood pressure. A three-fold increase in the dose of L-arginine further decreased blood pressure. On discontinuing the infusion of L-arginine, the patient's blood pressure increased. A female infant undergoing an L-arginine challenge test had a decrease in blood pressure during L-arginine infusion which resolved when the L arginine infusion was discontinued. These two cases suggest that nitric oxide production from L-arginine may play a role in the normal regulation of systemic blood pressure. PMID- 7795363 TI - Legislative approaches to assisted reproduction. PMID- 7795364 TI - Egg yolk enhances the receptiveness of zona pellucida to sperm binding. AB - PURPOSE: Our purpose was to test whether treatment of zona pellucida with egg yolk enhances its receptiveness to sperm binding. Hams F-10 supplemented with 0.06 g% freeze-dried egg yolk (TM) was evaluated using the hemizona assay. Ham's F-10 supplemented with 7.5% human serum served as the control medium (CM). Salt stored zona pellucida were bisected and each matched hemizona processed in either TM or CM for the preincubation study or both hemizona processed in CM for the coincubation study. TEST yolk-treated sperm from 10 ejaculates were then incubated with the hemizona preincubated in TM and CM but coincubated in CM or coincubated with hemizona in TM and CM. RESULTS: A significantly (P < 0.02) higher number of tightly bound sperm and hemizona index for the hemizona either preincubated or coincubated in TM compared to the respective hemizonae in CM were observed. PMID- 7795365 TI - Reproductive capacity of the nucleus of the male gamete after completion of meiosis. AB - PURPOSE: Our purpose was to investigate the possibility of achieving fertilization and subsequent normal embryonic development by injecting round spermatid nuclei into rabbit oocytes. RESULTS: Two-to four-cell-stage embryos developed after round spermatid nuclear injections into rabbit ooplasma could further develop in vitro up to the expanding blastocyst stage or in vivo up to complete gestation. CONCLUSION: The current findings show that the haploid set of chromosomes of round spermatid can pair with the chromosomes of the ootid to participate in complete fertilization and subsequent embryonic and fetal development. In addition, we suggest that postmeiotic modifications of the round spermatid are not required for the pairing of male gamete chromosomes with those of the ootid. PMID- 7795366 TI - Covering embryo cultures with mineral oil alters embryo growth by acting as a sink for an embryotoxic substance. AB - PURPOSE: Assisted reproductive technologies require the use of culture media for gametes and embryos. Culture media and conditions intended for use in human in vitro fertilization are tested prior to use by evaluating their ability to support normal development of mouse embryos. RESULTS: Development to blastocysts of two-cell mouse embryos was equivalent for embryos cultured in center well dishes alone (93 +/- 10%, mean +/- SD) and embryos cultured in center well dishes with an overlay of 1 ml of mineral oil (94 +/- 5%). In contrast, no development of two-cell-stage mouse embryos occurred in an embryotoxic medium when cultured in center well dishes. However, when this medium was covered with an overlay of mineral oil, development to blastocyst was no different than that of controls (96 +/- 5%). Similar results were found with cultures of one-cell-stage mouse embryos. CONCLUSION: These results indicate that in some circumstances the presence of mineral oil can significantly alter the outcome of embryo culture. Further, these results reinforce the necessity of directly testing the exact culture conditions to be used for assisted reproductive technologies. PMID- 7795368 TI - Minimal stimulation with simplified monitoring for in vitro fertilization. AB - PURPOSE: This retrospective, descriptive study was designed to determine the effectiveness of using clomiphene citrate in relatively high daily doses (100, 150, and 200 mg) with simplified monitoring for in vitro fertilization in a private office and surgical center. The self-selected study population comprised 109 women who were 25-42 years old, including 26 women whose husbands had mild male-factor infertility. RESULTS: During January 1992 through December 1993, 165 stimulation cycles resulted in 137 egg retrievals, 24 clinical pregnancies (17.5%), and 20 viable pregnancies (14.5%). Cycles that could not be completed (28/165 or 16.9% of all cycles) involved luteinizing hormone surges, insufficient follicles, or low estradiol levels. There were no pregnancies in patients who were 40 years or older or who received 200 mg daily doses of clomiphene citrate. The viable pregnancy rate among patients with male factor infertility was 7.7% (2/26). For non-male-factor infertility patients who were younger than 40, the viable pregnancy rate was 17.6% (18/102). CONCLUSION: The simplified monitoring method did not appear to compromise the results. PMID- 7795367 TI - The screening of embryonic viability in early asymptomatic pregnancy by a single endosonographic scan associated with plasma human chorionic gonadotropin determination. AB - PURPOSE: Our purpose was to assess, with a prospective study with random assignment of the day of the first evaluation, whether a single transvaginal ultrasonographic evaluation together with the determination of plasma hCG levels could be used to screen embryonic viability in early asymptomatic pregnancy. METHODS: In 260 pregnant women observed from January 1991 to November 1993 with spontaneous pregnancies where the exact date of ovulation was known, a single transvaginal ultrasonographic measurement of gestational sac with determination of plasma hCG levels, transformed to their natural logarithm (lnhCG), was performed. An abnormal result was defined as a value of lnhCG per mean gestational sac below the 95% lower confidence limit of the viable pregnancy group. RESULTS: The sensitivity was 31%, with a specificity of 97%. CONCLUSION: The study demonstrates that this method has a poor predictive capacity to distinguish viable pregnancy from nonviable pregnancy with a kappa value less than 0.4. PMID- 7795369 TI - The effect of dam's strain on the intrauterine craniofacial growth of mouse fetuses. AB - PURPOSE: The maternal effect is one of the important factors in mammalian growth in conjunction with the genetic effect. The present study investigated the prenatal maternal effect of a dam on the intrauterine craniofacial growth of a mouse fetus using embryo transfer and cephalometry. DDD/Qdj strain mouse embryos were transferred to four strains of recipient female mice (DDD/Qdj, C3H/Qdj, C57BL/Qdj, and DBA/1J Sea). Just after parturition cephalometric observation of the newborn offspring, which developed in the uteri of the four strains of dams, was performed and then the craniofacial size of the newborn offspring was calculated on the lateral cephalogram. Statistical analyses were performed to examine the correlation between the dam's weight and the craniofacial size of the newborn offspring, to test the significance of the effect of the dam's strain on the craniofacial size of the newborn offspring, and to evaluate the interstrain difference of the intrauterine craniofacial growth of the mouse fetuses. RESULTS: It was disclosed that there were a direct relation between the dam's weight and the craniofacial size of the newborn offspring, a significant effect of the dam's strain on the craniofacial size of the newborn offspring, and a significant interstrain difference in the craniofacial size of the newborn offspring after eliminating the effects of litter size and gestation period on the craniofacial size of the newborn offspring (DDD/Qdj > C3H/Qdj = C57BL/Qdj > DBA/1J Sea). CONCLUSION: Thus, it could be concluded that the four strains of dams affected differently the intrauterine craniofacial growth of the DDD/Qdj strain fetuses through each uterine condition, indicating that the dam's weight played an important role as one of the prenatal maternal effects on the intrauterine craniofacial growth of mouse fetuses. PMID- 7795370 TI - Coculture of mouse embryos with cryopreserved human oviduct epithelial cells. AB - PURPOSE: The effect of coculturing mouse embryos with cryopreserved human oviduct epithelial cells was investigated. The cryopreserved cells in Cellbanker were thawed and cultured in Richard D. Goldsby culture medium to establish monolayers. Two-cell-stage mouse embryos were cultured alone (control group) or cocultured with monolayers established from cryopreserved cells (cryopreserved coculture group) or from fresh cells (fresh coculture group). The rates of embryo development and the qualities of the blastocysts in the three groups were compared. RESULTS: The two coculture groups had significantly higher blastocyst development rates (cryopreserved coculture group, 81.6%; fresh coculture group, 82.2%) than the control group (63.1%). The two coculture groups had significantly more blastomeres (cryopreserved coculture group, 108.3 +/- 25.9; fresh coculture group, 108.4 +/- 25.1) than the control group (87.7 +/- 31.9). CONCLUSION: The method of cryopreservation of human oviduct epithelial cells using Cellbanker is simpler than conventional cryopreservation methods. These cryopreserved human oviduct epithelial cells may provide a constant supply of cells for coculture for in vitro fertilization and embryo transfer. PMID- 7795371 TI - Transabdominal embryoscopy for the detection of Carpenter syndrome during the first trimester. PMID- 7795372 TI - Vitamin supplements improve the fertility potential of a subfertile male with macrocytic anemia--a case study. PMID- 7795373 TI - Evaluation of endocarditis and its complications by biplane and multiplane transesophageal echocardiography. AB - Echocardiography is currently the method of choice for the diagnosis of endocarditis-associated vegetations or complications such as abscess formation. Thereby, the transesophageal approach (TEE) is clearly superior to precardial echocardiography and, at present, biplane TEE can be considered as the standard TEE technique. Compared with the monoplane technique, biplane TEE provides additional qualitative and quantitative information concerning the presence and amount of valvular destruction. Multiplane TEE facilitates (and abbreviates) the examination procedure, and may be helpful for easier detection of small initial abnormalities, those developing on native valves with preexisting lesions, or on prosthetic valves. It allows more accurate measurements and three-dimensional reconstruction of vegetations and abscess areas and provides more anatomical details of the disease. However, it remains to be shown by future studies if multiplane TEE will identify endocarditis-associated lesions more frequently than the biplane technique doses. PMID- 7795374 TI - Transesophageal echocardiography in the evaluation of prosthetic valves. AB - Biplane and multiplane TEE, with its relatively low risk, has become an invaluable complement to a comprehensive transthoracic two-dimensional Doppler and color flow examination. It should be undertaken in all instances when the transthoracic information is not adequate or if there is suspicion of abnormality that is not detected by TTE. One can advocate the use of TEE in the operating room in all instances wherein a patient is going to be implanted with a prosthetic valve because it will permit one to obtain baseline information that may be valuable in the management of patients seen subsequently with questionable findings when comparison is valuable. The role of cardiac catheterization is limited. Hemodynamic cardiac catheterization should only be used in instances in which there is discrepancy between echocardiographic findings and clinical presentation. Visualization of coronary arteries may be indicated in some situations, and a limited coronary arteriogram could be performed, the procedure being less morbid if separated from hemodynamic right and left heart catheterization. Echocardiography represents the state of the art in evaluation of patients with valvular prosthesis. Biplane TEE and multiplane TEE are valuable complementary technology to be used in conjunction with TTE, when the situation dictates its use, because it provides useful information that alters management of the patient. PMID- 7795375 TI - Advantages of biplane and multiplane transesophageal echocardiography for the morphology of the aorta. PMID- 7795377 TI - Biplane and multiplane transesophageal echocardiography: evaluation of congenital heart disease. AB - Congenital heart disease can be a diagnostic challenge. Transesophageal echocardiography (TEE) has markedly extended the diagnostic power of the ultrasound examination. Outpatient TEE is most useful in the assessment of adult congenital heart disease. Outside the acute care setting, TEE is not commonly used to diagnose pediatric congenital heart disease. Most anomalies can be accurately assessed with transthoracic echocardiography. In the intensive care unit, cardiac catheterization laboratory, and operating room, TEE is used in patients of all ages to assess the anatomic and functional spectrum of preoperative and postoperative congenital heart disease. A consistent anatomic presentation is used to show various congenital cardiac anomalies. PMID- 7795376 TI - Multiplane transesophageal echocardiographic evaluation of mitral valve disease. AB - With the additional ability to rotate the image around the axis of the centerline of the sector, multiplane transesophageal echocardiography (TEE) improves over single or biplane TEE in ease of use and diagnostic accuracy. This article reviews the anatomic, physiological, and topographic considerations that affect the use of multiplane TEE in evaluation of patients with mitral valve disease. The optimum mitral valve examination includes a true "short-axis" view, obtained by a transverse (zero-degree angle) transgastric image orientation with the probe tip flexed anteriorly, and several "long-axis" views, obtained from various rotations of the basilar multiplane TEE image planes. This provides a useful and accurate means to determine the mechanism of mitral regurgitation, which is useful in planning and timing, determining the likelihood, and predicting the surgical techniques that will be required for mitral valve repair. The postcardiopulmonary bypass (postpump) TEE examination in a patient with mitral regurgitation is a second important component of the process of repair, to determine the presence and severity of residual mitral regurgitation, and identify any complications of surgery. Of 1,550 mitral repair operations studied with postpump echocardiography at our hospital since 1987, a total of 105 (7%) have had second pump runs. Multiplane TEE is also useful to pinpoint the exact site of periprosthetic regurgitation around a mitral prosthesis, enabling direct surgical closure in some cases. Understanding special technical features of multiplane TEE is an important component for optimum utilization of this powerful diagnostic modality. PMID- 7795378 TI - Improved detection of wall motion by transesophageal stress echocardiography using a biplane transducer. AB - Transesophageal stress echocardiography using simultaneous transesophageal atrial pacing or pharmacological agents, eg, dobutamine, is a valuable addendum to conventional stress echocardiography. Initial experiences with combined transesophageal echocardiography (TEE) and atrial pacing or during pharmacological infusion are reported with monoplane techniques. Potential advantages of biplane application can be expected in detection or exclusion wall motion abnormalities (WMA). Twenty-one consecutive patients underwent transesophageal stress echocardiography with a biplane transducer. WMA were observed in 19 patients. In 9 of 19 patients (47%) the transverse plane was the only diagnostic section for WMA; the longitudinal plane was the only diagnostic section in 3 of 19 patients (additional yield: 16%). In 7 patients (37%), both planes were diagnostic. Thus, advantages include a higher diagnostic yield compared with monoplane TEE because of better visualization of basal and apical segments. An important limitation of the biplane probe during transesophageal atrial pacing is its restricted mobility. Using pharmacological agents, the ventricle can be monitored from the transgastric as well as from the transesophageal position. Transesophageal stress echocardiography using a biplane transducer is feasible, and allows more successful imaging of the regional basal and apical segments compared with the monoplane technique and increases its diagnostic yield. In conjunction with transesophageal atrial pacing, the biplane technique is limited to one single position only because of restricted mobility during the entire stress procedure. PMID- 7795379 TI - Three-dimensional reconstruction of cardiac structures from transesophageal echocardiography. AB - Although tomographic imaging has been very successful in cardiology,the quantitation of volumes, surfaces, and masses,as well as understanding of complex morphologies would improve by three-dimensional imaging. This review focuses on approaches to 3-D reconstruction from transesophageal echocardiography. In the past, several attempts using either stepwise parallel translation or stepwise rotation of the transducer have been made. In vitro and, to a limited extent, in vivo studies have confirmed high accuracy in calculating left ventricular volumes in such manner. Complex cardiac structures and their motion, such as the mitral annulus, mitral leaflets, atrial septal defects, and others have been reconstructed from patient studies. Although potentially a powerful tool for cardiac imaging with promising quantitation capabilities, progress is needed in particular in the field of border detection to make 3-D imaging practical enough for clinical use. PMID- 7795381 TI - Standard views in cardiac multimodality tomographic imaging. AB - In cardiology, it is often necessary to acquire more than one type of image to investigate a given clinical problem of a single patient. Images obtained from different imaging modalities are usually recorded and displayed in different orientations, at different positions, and at different scale factors. It is then necessary for the physician to mentally integrate the image information from the different imaging modalities. This phenomenon is particularly true with tomographic imaging techniques that allow complete freedom of the acquisition plane. In particular, when comparing images obtained from ultrasound, computed tomography, magnetic resonance imaging, positron-emission tomography, and single photon emission computed tomography. The purpose of this article is to propose a standard set of slice orientations that could be easily applied to all modalities. Such common views could greatly facilitate the user's perception of the regional abnormalities observed in the different imaging modalities. This standardization is certainly useful for clinical application but also for every research study that requires a comparative evaluation of the different imaging modalities. Although exact registration of the images from the different modalities requires sophisticated computer programs, the simple reference method in plane positioning proposed here based on plane orientation according to the cardiac geometry can certainly provide a practical and convenient method for the reasonably accurate image registration required for visual comparative studies. PMID- 7795382 TI - Transesophageal transducer technology: an overview. AB - Early developments and basic principles in the field of Transesophageal Echocardiography (TEE) probe technology are summarized. Mechanical and electronical sector scanners are compared, and several probe characteristics and image parameters are discussed. A short review of recent developments in TEE is given. PMID- 7795383 TI - Biplane and multiplane transesophageal echocardiography: methodology and echo anatomic correlations. AB - Transesophageal echocardiography (TEE) is one of the most significant developments in cardiology and cardiac imaging in the last decade. While monoplane TEE clearly showed the advantages of imaging from the esophagus, biplane TEE was the next important step forward. The combination of transverse and longitudinal axis images served to provide incremental information about various cardiac pathologies. Multiplane TEE is a further advancement that allows continuous visualization of cardiac anatomy by electronic or manual steering of the ultrasound beam through 180 degrees. The intermediate views obtained by beam steering provides an unlimited perspective of normal and abnormal cardiac anatomy. This ability to view cardiac structures in multiple planes aids the understanding of the spatial arrangement of normal cardiac structures and complex disorders of cardiac anatomy. Multiplane TEE technology also eases the examination by reducing the need for probe manipulation. The ability to obtain multiplane images in a sequential manner lays the foundation for three dimensional imaging of the heart. Ongoing developments in transducer technology should further strengthen the clinical role of TEE. PMID- 7795380 TI - Reliability of electron beam computed tomography to detect coronary artery calcification. AB - Electron beam computed tomography (CT) provides a safe, rapid, and noninvasive means to detect the presence and quantitate the deposition of calcium in the coronary arteries. To examine the reproducibility of a coronary calcification screen using electron beam CT, 50 subjects underwent two studies, averaging 12 minutes between studies. The number, volume, and calcification scores were determined for each artery as well as a total score of coronary calcification. Thirty-four of the 50 subjects had evidence of coronary calcification. The reliability score for total coronary artery calcification was 0.99. The reliability score for the total number of lesions and total volume was at or above 0.98. There were 8 cases in which a negative calcium score on retest was positive or where a positive calcium score on retest was negative. In both instances, the amount of calcium detected was very small. Therefore, evidence suggests that electron beam CT is reliable in the detection of coronary artery calcification and may be a useful tool for the early detection of coronary atherosclerosis before flow impairment. PMID- 7795385 TI - Occurrence of D-aspartic acid in rat brain pineal gland. AB - We found a high concentration (1030 pmol per pineal gland) of D-aspartic acid (D Asp) in the pineal gland of 6-week-old Sprague-Dawley (SD) rats. The content of D Asp decreased with age, being 210 and 33 pmol per pineal gland in 28- and 45-week old rats respectively. The proportion of D-Asp [(D-Asp/total Asp) x 100] also decreased with age, declining from 66% to 10% between 6 and 45 weeks after birth. The proportion of D-Asp did not differ between the sexes. The concentration of D Asp was higher at night (at 2.00 a.m. 2830 +/- 485 pmol per pineal gland) than during the day (at 10.00 a.m. 1030 +/- 200 and at 3:00 p.m. 682 +/- 194 pmol per pineal gland), suggesting that biosynthesis of D-Asp in the pineal gland occurs at night. D-Asp was found to be distributed in the cytosol of pinealocytes, but its biological role remains unclear. PMID- 7795384 TI - Determination of chondroitin sulphates in human whole blood, plasma and blood cells by high-performance liquid chromatography. AB - A simple HPLC method for determination of chondroitin sulphates as their unsaturated disaccharides by chondroitinases has been applied to measure the glycosaminoglycans (GAGs) in human whole blood, plasma and blood cells. This method may be useful for the investigations on the role of blood GAGs and the metabolic fates of the exogenous GAG. PMID- 7795387 TI - N-glycosylation site mapping of recombinant tissue plasminogen activator by micellar electrokinetic capillary chromatography. AB - This report describes the N-glycosylation mapping of recombinant tissue plasminogen activator (rt-PA) using micellar electrokinetic capillary chromatography. The carbohydrate structures were tentatively assigned by comparison with the anion-exchange fractionated oligosaccharides and by a comparison with previously reported data. The separation was shown to rely mainly on the degree of sialylation of the oligosaccharides, allowing a quantitative determination of the proportion of neutral and mono- to tetrasialylated structures. Significant differences in the oligosaccharide distribution of the two variants of rt-PA, which differ by the presence (type I) or the absence (type II) of oligosaccharides at the Asn-184 site, were observed. The distribution of the oligosaccharides at each of the rt-PA glycosylation sites was then determined. Glycopeptides were prepared by tryptic digestion of rt-PA and isolated using two consecutive chromatographic procedures. The glycopeptides were finally treated with N-glycanase, and the resulting oligosaccharides were analysed by capillary electrophoresis. Oligosaccharide mapping revealed that the Asn-448 and Asn-184 sites carry the same population of complex-type oligosaccharides but that the relative amounts of each oligosaccharide vary markedly. High-pH anion-exchange chromatography performed on the desialylated oligosaccharides at each glycosylation site showed that the degree of microheterogeneity was related not only to the degree of sialylation but also to structural differences in the oligosaccharide sequences. From the results as a whole, we concluded that the Asn-448 site contains a greater proportion of heavily sialylated structures and has a higher degree of microheterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795386 TI - Reversed-phase high-performance liquid chromatography of fullerenes with tetrahydrofuran-water as a mobile phase and sensitive ultraviolet or electrochemical detection. AB - Fullerenes (C60 and C70) were separated on a reversed-phase high-performance liquid chromatography column with a mobile phase of tetrahydrofuran-water (70:30, v/v) and detected with ultraviolet or electrochemical detection. A baseline resolution of C60 and C70 was achieved with a capacity factor values of 7.6 and 10.8 respectively and a resolution of 3.7. The detection limit for C60 was 0.1 pmol on column and was nearly the same for both detection methods. PMID- 7795389 TI - High-performance liquid chromatographic assay for the quantitation of nadolol in human plasma using fluorescence detection. AB - A rapid and sensitive HPLC-fluorescence assay was developed and validated for the determination of nadolol, a beta-blocker, in human plasma. Nadolol and the internal standard (desmethyl nadolol) were extracted from alkalinized plasma into methyl-tert.-butyl ether. The organic solvent was evaporated under nitrogen at 40 degrees C. The residue was reconstituted in the mobile phase and injected on to a C18 silica column (25 cm x 4.6 mm i.d.) at a flow rate of 1.4 mL/min. The mobile phase was 0.05 M monobasic ammonium phosphate (pH 4.2) and acetonitrile (84: 16, v/v). Fluorimetric detection was performed at excitation 230 nm and emission 330 nm. The nominal retention times were 3.3 and 4.3 min for the internal standard and nadolol, respectively. The lower limit of quantitation was 5 ng/mL and linearity (R2 > or = 0.994) of the standard curve was demonstrated between 5 and 500 ng/mL. The analysis of quality control (QC) samples at 60, 200 and 400 ng/mL resulted in precision estimates < or = 7.0% relative standard deviation (RSD) for the inter-assay and < or = 6.3% RSD for intra-assay. The predicted concentrations of the QC samples deviated < 10% from the nominal values. The extraction recovery of nadolol from human plasma was 64%. Nadolol was stable in human plasma at -20 degrees C for at least 5 months and for at least three freeze-thaw cycles. Nadolol and the internal standard were stable in the autosampler at 5 degrees C for at least 40 h. Overall, the assay was accurate, precise, sensitive, specific, and reproducible for the analysis of nadolol in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795388 TI - Investigation of enantioselective ofloxacin-albumin binding and displacement interactions using capillary affinity zone electrophoresis. AB - The direct chiral separation of ofloxacin by capillary affinity zone electrophoresis using serum albumins from different animal sources as chiral selector in the supporting electrolyte is described. In addition, the effects of displacers on the mobility and enantioselectivity of ofloxacin were studied. Firstly, the separation behaviour of the enantiomers of the ofloxacin (OFLX) and tryptophan (Trp) was compared. The influence of albumin types, including chemically modified bovine serum albumins (BSAs), and buffer types on the migration behaviour of enantiomers was investigated. The results showed that stereoselectivity of Trp is independent of the type of albumin used. However, chiral separation of OFLX depends on the biological species of albumin. Use of chemically modified BSA led to poorer resolution of enantiomers. Only with acetylated BSA could chiral separation of Trp be achieved. Using Good's buffer solutions (DIPSO and HEPES) as a supporting electrolyte affected the migration times of OFLX enantiomers. Finally, a variety of displacers were added to the buffer along with the protein, and the effects on separation behaviour were observed. The displacers included warfarin, ketoproten, diazepam, propranolol, benzoinphenylbutazone, digitoxin and octanoic acid. From the results obtained, it is concluded that capillary affinity zone electrophoresis using albumin as a chiral selector may allow screening of OFLX-displacer interactions. PMID- 7795390 TI - Dye-ligand affinity chromatography on continuous beds. AB - Continuous beds derivatized with three triazine dyes (Cibacron Blue 3G-A, Pricon Red HE-3B and Pricon Red H-3B) were used for chromatographic purification of dehydrogenases from yeast enzyme concentrate. All three columns, which were prepared by a very simple and cost-effective method, provided strong binding of glucose-6-phosphate dehydrogenase and lactate dehydrogenase. The Cibacron Blue 3G A column showed high affinity for alcohol dehydrogenase. Under the same conditions, the Pricon Red HE-3B column showed a lower affinity and the Pricon Red H-3B column showed none. The adsorbed dehydrogenases were eluted specifically from the columns in high yields (71-113% by desorption with the coenzymes NADP, NADH and NAD respectively). Non-specific binding of human serum albumin and transferrin to these columns was also investigated. Enzyme assays and analyses by capillary electrophoresis showed that the continuous beds derivatized with triazine dyes gave a high degree of purification. PMID- 7795391 TI - Determination of glutathione and related aminothiols by gas chromatography with flame photometric detection. AB - A selective and sensitive method for the determination of glutathione (GSH) and related aminothiols such as cysteine (Cys), cysteinylglycine (CysGly) and gamma glutamylcysteine (gamma-GluCys) by gas chromatography (GC) has been developed. GSH and related aminothiols were converted into their N,S-isopropoxycarbonyl methyl ester derivatives and measured by GC with flame photometric detection using a short capillary column (5 m x 0.53 mm i.d.) of cross-linked DB-1. The calibration curves were linear in the range 1-25 nmol for GSH and in the range 0.2-5 nmol for other aminothiols, and the detection limits of GSH, Cys, CysGly and gamma-GluCys were approximately 5, 0.2, 0.3 and 0.5 pmol per injection respectively. This method was successfully applied to blood samples without prior clean-up, and GSH and related aminothiols in these samples could be analysed without any influence from coexisting substances. Overall recoveries of GSH and other aminothiols added to blood samples were 88-107%. The analytical results of free and total blood GSH and related aminothiols in normal subjects are presented. PMID- 7795392 TI - High-performance liquid chromatographic separation of penicillamine enantiomers labelled with N-[4-(6-dimethylamino-2-benzofuranyl)phenyl] maleimide on a chiral stationary phase. AB - Penicillamine enantiomers derivatized with N-[4-(6-dimethylamino-2 benzofuranyl)phenyl]maleimide (DBPM) were separated and determined by high performance liquid chromatography. A fluorogenic reagent, DBPM easily reacted with D- or L-penicillamine to give each two kinds of strong fluorescent derivatives (D1-, D2-, L1- and L2-DBPM), which could be separated on a Pirkle type chiral stationary phase using an eluent of 75% aqueous methanol solution containing 0.15 M CH3COONH4 and 0.05 M tetra-n-butylammonium bromide. Two of the peaks (D1- or L1-DBPM), having a shorter retention time than the others, had almost the same retention times (25 min for D1-DBPM and 25.7 min for L1-DBPM). The retention times of the peaks eluted later were 28 min and 31.6 min for D2- and L2-DBPM respectively. Linear calibration curves over the range of 2-50 pmol per injection were obtained for D- and L-penicillamines with a detection limit of 290 and 350 fmol at respectively at a signal-to-noise ratio of 3. Using the proposed method, the absence of contamination of L-penicillamine in a commercially available D-penicillamine preparation (capsule) was confirmed. PMID- 7795393 TI - A sensitive high-performance liquid chromatographic assay for the cholecystokinin B antagonist, CI-988, in human and monkey plasma. AB - A sensitive and specific high-performance liquid chromatographic assay for the non-peptide cholecystokinin subtype B receptor antagonist, CI-988, in human and cynomolgus monkey plasma has been developed and validated. The method involves isolation of CI-988 and internal standard by batch robotic solid phase extraction with a C18 cartridge, liquid chromatographic separation on a C18 column and quantitation by fluorescence detection. The human plasma assay is linear from 0.25 to 500 ng/mL for a 1.00-mL plasma aliquot. Assay precision for CI-988 based on human plasma quality control samples was within +/- 7.2% relative standard deviation with an accuracy of +/- 5.6% relative error. The monkey plasma assay is linear from 1.00 to 250 ng/mL for a 0.500-mL plasma aliquot. Assay precision based on monkey plasma quality control samples was within +/- 11.0% relative standard deviation with an accuracy of +/- 2.6% relative error. PMID- 7795394 TI - Direct separation of tranylcypromine enantiomers and their profile in an atypical depressive patient. AB - An isocratic and simple high-performance liquid chromatographic method is developed for the direct resolution of the tranylcypromine (TCP) enantiomers. The method involves the use of an S-18-crown-6-ether chiral stationary phase known as the Crownpak CR (+) column. The stereochemical separation factor (alpha) obtained was 1.30 and the stereochemical resolution factor (Rs) was 0.69 when using a mobile phase consisting of 0.1 N perchloric acid containing 12% methanol at 23 degrees C. The method has been used to monitor and identify, qualitatively, the profile of enantiomers of TCP in urine of an atypical depressive patient. It was found that the (-)-S-TCP concentration is significantly higher than the (+)-R enantiomer. PMID- 7795395 TI - Myopia and stature: findings in a population of 106,926 males. AB - We conducted a nation-wide study of the relationship of myopia with height, weight and body-mass index in order to confirm observations that myopic persons are taller than non-myopes. From a review of the data of 106,926, consecutive male military recruits aged 17 to 19 years, we found that myopia is associated neither with higher stature nor with greater weight. Persons with severe myopia were slightly shorter (172.8 +/- 7.1 cm) and weighed less (62.6 +/- 11.0 kg) than those with mild myopia (173.3 +/- 6.9 cm and 63.8 +/- 10.5 kg respectively), while the non-myopes were taller (173.7 +/- 6.7 cm) and heavier (63.9 +/- 10.2 kg) than the myopes (p = 0.0001). The mean body-mass index was only slightly smaller among the myopes (21.1 +/- 3.1 kg/m2) than among the non-myopes (21.2 +/- 2.9 kg/m2, p = 0.0001). PMID- 7795396 TI - Fluorophotometric study of lens autofluorescence and the blood-retinal barrier in 56 diabetic patients. AB - We examined lens autofluorescence and the permeability of the blood-retinal barrier in 56 diabetic patients (34 insulin-dependent and 22 non-insulin dependent), using the Fluorotron Master (R), a commercially available fluorophotometer. Significant relationships were found between age and lens autofluorescence (p < 0.01), between duration of diabetes and lens autofluorescence in insulin-dependent diabetics (p < 0.01), and between duration of diabetes and blood-retinal barrier permeability in all diabetics (p < 0.05). The relationships between lens autofluorescence and duration of diabetes in non insulin dependent patients (p > 0.05), and between lens autofluorescence or the penetration ratio and HBA Ic during the five preceding years (p > 0.05) were not significant. Fluorophotometry provides an objective and reproducible method for in vivo investigation of the ocular complications of diabetes and of the factors influencing them. PMID- 7795397 TI - Effect of oral captopril (SQ 14225) on intraocular pressure in man. AB - The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound. PMID- 7795398 TI - Conjunctival fibrosis after application of mitomycin C: an animal experimental study. AB - Mitomycin C (MMC) is widely used as an antimetabolite to minimize scarring of filtering blebs. Its effectiveness has been demonstrated in several clinical studies. The drug's mechanism of action is attributed to its antiproliferative effect on the subconjunctival cells, reducing the wound healing response. We placed sponges soaked with various concentrations of MMC, from 0.05 to 1.0 mg/ml, under the conjunctiva of 18 rabbits. Four weeks later, there was marked concentration-dependent scarring of the substantia proppria of the conjunctiva. Macrophages were more numerous in treated eyes, as determined by immunohistochemistry. The reason for MMC-related fibrosis in this animal model is not clear but may be related to the substances toxic effects. Whether it is only present in rabbits remains to be clarified. PMID- 7795399 TI - Contact transscleral cyclophotocoagulation with diode laser in refractory glaucoma. AB - OBJECTIVE: To evaluate the clinical effectiveness of contact transscleral cyclophotocoagulation (CTCP) with diode laser. DESIGN AND PATIENTS: Forty-eight seeing eyes and 20 blind and painful eyes of 68 patients suffering from refractory glaucoma were treated using a diode laser (EOS3000, Laser Science) coupled with a 400-microns optic fiber ending in a 3-mm focusing tip. Sixteen to twenty 3.9-J (2.6 W x 1.5 to 2.5 s) laser spots were placed over 360 degrees, 1.5 mm from the corneolimbal junction. RESULTS: In the seeing-eye group, the follow up was 20.7 +/- 8.14 months, pre- and posttreatment IOPs were 37.1 +/- 11.27 and 19.5 +/- 8.73 mmHg respectively (p < 0.0001), and success (IOP > 2 and < or = 21 mmHg) was 70.8%. No significant visual acuity change was found in the successful eyes, whereas a significant visual acuity reduction was found in the unsuccessful cases (p = 0.03). In the blind-eye group, the follow-up was 20.5 +/- 8.54 months, pre- and post-treatment IOPs were 50.7 +/- 15.05 and 20.6 +/- 13.99 mmHg respectively (p < 0.0001), and success (remission of pain) was 100%. As for complications, one seeing eye developed a spontaneously-resolved vitreous hemorrhage and one seeing and one blind eye became hypotonic, though no phthysis was observed. No conjunctival or lens damage was detected, and no scleral thinning was revealed by ultrasound biomicroscopy. No case of sympathetic ophthalmia was found. CONCLUSIONS: Diode laser can be successfully employed for CTCP in refractory glaucoma. PMID- 7795400 TI - Factors predisposing to postoperative intraocular inflammation. AB - This prospective study of 123 patients undergoing cataract extraction determined the preoperative and surgical factors predisposing to an exaggerated postoperative inflammatory response. It is important to identify the patients at increased risk of complications requiring additional prophylaxis or more intensive postoperative care, particularly when selecting patients for day case surgery. Previous intraocular inflammation or surgery was the factor most strongly associated with marked inflammation on the first postoperative day (p < 0.01, compared to uncomplicated patients). As a result, patients stayed in hospital an average of one day longer (p < 0.001) and required significantly more steroid drops (p < 0.001). Other factors of significance, but reducing importance were: difficult surgery, non-caucasian race and brown irides. Amongst uncomplicated patients, the difficulty of surgery was most significantly related to a high inflammation score (p < 0.01). Non-caucasian patients stayed in hospital significantly longer than their caucasian counterparts (p < 0.05), and required more steroid drops (p < 0.001). Of caucasian patients, those with brown irides were inpatients for significantly longer than those with blue or hazel (p < 0.05). No other factors studied significantly altered postoperative inflammation: neither the presence of diabetes, nor the technique of cataract extraction. PMID- 7795401 TI - Surgical removal of subretinal neovascular membranes. AB - Since 1991 we have been gaining experience in the surgical removal of submacular subretinal membranes in patients with presumed ocular histoplasmosis syndrome (POHS), idiopathic subretinal neovascularisation, myopia and age-related macular degeneration (AMD). Seventeen patients were operated between 1991 and 1993. Significant improvement of vision was achieved in 4 out of 5 patients with POHS, 3 out of 5 with idiopathic neovascularisation, 2 out of 4 with myopia but none of 3 patients with AMD. The results suggest that subretinal neovascularisation can be successfully removed in POHS and in some forms of idiopathic neovascularisation and myopia but probably not in AMD. PMID- 7795402 TI - Pathogenesis of primary internal ophthalmoplegia after head injury. AB - Primary internal ophthalmoplegia is a rare ocular syndrome after head injury. Its pathogenesis remains unclear and it is only a hypothesis that the pupillomotor fibres on the ventromedial aspect of the oculomotor nerve are slightly contused against the petroclinoid ligament at the moment of impact. We observed a patient after head injury who presented with a fixed, dilated pupil and died within 15 hours of the accident. The postmortem examination revealed an isolated group of fibres on the medial aspect of her oculomotor nerve, which had been torn out of the midbrain. This suggests an alternative explanation in terms of partial injury to the oculomotor nerve to account for primary internal ophthalmoplegia. PMID- 7795403 TI - Relapsing bilateral uveitis and papilledema in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). AB - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non hereditary histiocytic proliferative disorder affecting young people, with extranodal manifestations in 28-43% of cases. Eye involvement is infrequent. Lymphoproliferation in the soft tissues of the orbit and in the lids has been reported in 12% of cases but intraocular involvement is rare. We describe the case of a 12-year-old boy affected by Rosai-Dorfman disease with bilateral relapsing uveitis and papilledema that appeared four years before the onset of lymphadenopathy. PMID- 7795404 TI - The use of continuous pupillary dilatation of a blind born child in the early 8 months, to achieve partial recovery of vision. PMID- 7795405 TI - The role of serum calcium in the development of the acute red eye in chronic renal failure. AB - In patients with chronic renal failure treated by long-term dialysis, inflammatory reactions occasionally develop in the bulbar conjunctiva; the episcleral tissue is only rarely involved. Diffuse congestion of both the conjunctiva and episclera was present in 5.3% of our patients and was associated with a sudden, marked rise in serum calcium. Histopathological examination suggests that this form of hyperemia, clinically preceded by a marked shedding of calcific precipitates, is the result of a neurogenic-driven inflammatory reaction in which mast cell degranulation is mediated by the axon reflex. Focal hyperemia associated with elastosis ("pingueculitis") was present in 6.7% of the patients. This type of hyperemia was observed after an extended period of increasing levels of BUN and seemed independent of both serum calcium and phosphorus. Diffuse hyperemia of the conjunctiva, being clinically distinctly different from the combined diffuse conjunctival and episcleral hyperemia, was also observed in 6.7%. Diffuse conjunctival hyperemia seemed to be associated with low BUN. Here, again, there was no association with serum calcium and phosphorus levels. PMID- 7795406 TI - 3rd International Workshop on Carcinoma-Associated Mucins, August 7-11 1994, Cambridge, UK. PMID- 7795407 TI - Molecular Cell Biology of Cytokines and Matrix, September 21-23 1994, Cardiff, UK. PMID- 7795408 TI - Importance of lectins for the prevention of bacterial infections and cancer metastases. AB - Adhesion of bacteria and of metastasizing tumour cells have much in common, especially the participation of lectins in this process. In the future it might be possible to inhibit the metastatic process and bacterial adhesion by blocking with lectins specific for appropriate (oligo) saccharides or glycoconjugates. Initial clinical trials are very promising. PMID- 7795410 TI - Lectins and also bacteria modify the glycosylation of gut surface receptors in the rat. AB - Oral exposure to lectins or the presence or absence of bacteria in the rat small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken together with the dramatic effects of exposure to lectins on gut function, metabolism and bacterial ecology, this can be used as a basis for new perspectives of biomedical manipulations to improve health. PMID- 7795409 TI - Isolation of a melibiose-binding protein from human spleen. AB - A melibiose-binding protein was isolated from human spleen by serial affinity chromatography on lactose-, mannose-, and melibiose-Sepharose. The purified protein agglutinated rabbit erythrocytes and re-bound to melibiose, but did not bind to murine nor human laminin. The protein was composed of approximately 58 kDa and 26 kDa polypeptides. The polypeptides were detected in buffy coat cell extracts and they were synthesized in vitro by B lymphoblastoid cells. The polypeptides did not react with anti-galaptin, anti-C-reactive protein, anti amyloid P, anti-keratin, and anti-rat lung lectin 29 sera. The 58 kDa polypeptide reacted very weakly with anti-core-specific lectin serum and reacted with anti IgG serum. The data suggest that the major protein isolated is an anti-Ga1 alpha 1-->6 immunoglobulin. PMID- 7795412 TI - Water-soluble poly(acrylamide-allylamine) derivatives of saccharides for protein saccharide binding studies. AB - Water-soluble poly(acrylamide-allylamine) copolymers containing covalently bound amino groups, prepared by copolymerization of acrylamide and allylamine, can be used as general carriers for coupling of different types of saccharides or saccharide derivatives. The water-soluble macromolecular carbohydrate derivatives can be easily labelled and used in various solid-phase techniques to study protein-saccharide interaction. Two types of coupling reaction were used to prepare polyacrylamide derivatives of saccharides: reductive amination was applied to couple the reducing disaccharides and a carbodiimide reaction was used to couple heparin via its carboxyl groups to the amino groups of the poly(acrylamide-allylamine) derivative. Peroxidase labelled or biotinylated derivatives were shown to be useful in studies on the binding properties of lectins and proteins from boar seminal plasma. PMID- 7795413 TI - Use of sialylated or sulfated derivatives and acrylamide copolymers of Gal beta 1,3GalNAc alpha- and GalNAc alpha- to determine the specificities of blood group T- and Tn-specific lectins and the copolymers to measure anti-T and anti-Tn antibody levels in cancer patients. AB - Sialylated or sulfated derivatives and acrylamide copolymers of blood group T (Gal beta 1,3GalNAc alpha-) and Tn-(GalNAc alpha) haptens were studied for their interaction with the lectins of peanut (PNA), Agaricus bisporus-(ABA), Helix pomatia-(HPA) and Vicia villosa B4-(VVA), using asialo Cowper's gland mucin (ACGM), which contains both T and Tn epitopes, as the coating substrate in enzyme linked lectin assay. Both T and Tn copolymers (-40 haptens) showed high affinity and strict specificity; although the T-copolymer at 0.05-0.07 microM concentration caused 50% inhibition of interaction of either PNA or ABA with ACGM, there was little inhibition of the HPA and VVA interactions even at over 100 times that concentration. The Tn-copolymer at 0.02-0.05 microM inhibited HPA or VVA interaction with ACGM by 50% but gave virtually no inhibition of PNA and ABA binding. Sialyl, sulfate or methyl group substitution on C-6 of GalNAc of the T-haptene did not prevent interaction with PNA but almost abolished interaction with ABA. In contrast, sialyl or sulfate group on C-6 and sulfate on C-3 of Gal in Gal beta 1,3GalNAc alpha- inhibited almost completely the interaction of PNA with ACGM but had only a slight effect on the interaction of ABA; C-6 substitution with either sialic acid or sulfate on GalNAc alpha- almost abolished the interaction of both HPA and VVA with ACGM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795414 TI - Synthesis of an endogeneous lectin, galectin-1, by human endothelial cells is up regulated by endothelial cell activation. AB - The pattern of expression of an endogenous lectin, galectin-1, was examined in human lymphoid tissue. Galectin-1 was detected in the endothelial cells lining specialized vessels, termed high endothelial venules, in activated lymphoid tissue, but not in a resting lymph node. Cultured endothelial cells (human aortic and umbilical vein endothelial cells (HAECs and HUVECs)) expressed galectin-1. Activation of the cultured endothelial cells increased the level of galectin-1 expression, as determined by ELISA. Northern blot analysis and high throughput cDNA sequencing. These results suggest that galectin-1 expressed by endothelial cells may bind to and affect the trafficking of cells emigrating from blood into tissues. PMID- 7795411 TI - alpha 1,3-Fucosylation of branched blood group I-type oligo-(N acetyllactosamino)glycans by human milk transferases is restricted to distal N acetyllactosamine units: the resulting isomers are separated by WGA-agarose chromatography. AB - A partially purified preparation of alpha 1,3-fucosyltransferase(s) from human milk was used to [14C]fucosylate oligosaccharides containing Gal beta 1-4GlcNAc units. Substitution of N-acetyllactosamine at position 3' with a beta-linked N acetyl-glucosamine enhanced the reactivity of the acceptor, whereas similar substitution at position 6' was inhibitory. Thus, the trisaccharide GlcNAc beta 1 6Gal beta 1-4GlcNAc (5), the branched tetrasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc (11) and the triply branched decasaccharide GlcNAc beta 1 3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3[GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4GlcNAc (26) gave remarkably poor yields of alpha 1,3-fucosylated products in comparison to GlcNAc beta 1-3Gal beta 1-4GlcNAc (3). beta 1,4-Galactosyl derivatives of 5 and 11, however, gave good yields of alpha 1,3-fucosylated products, but the fucosylation was restricted to the distal N-acetyllactosamine units of Gal beta 1-4GlcNAc beta 1-6Gal beta 1-4GlcNAc (16), Gal beta 1-4GlcNAc beta 1-3(Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (18) and also in Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta 1 4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (22). Immobilized wheat germ agglutinin (WGA), possessing high affinity for 16 [1], revealed no affinity for the fucosylated derivative Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-6Gal beta 1 4GlcNAc (17). The isomeric heptasaccharides Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3(Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (19) and Gal beta 1 4GlcNAc beta 1-3[Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-6]Gal beta 1-4GlcNAc (20) were readily separated from each other on WGA agarose, and so were the isomeric nonasaccharides Gal alpha 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1 3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (23) and Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3[Gal alpha 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-6]Gal beta 1-4GlcNAc (24). PMID- 7795415 TI - Strategy for the investigation of O-linked oligosaccharides from mucins based on the separation into neutral, sialic acid- and sulfate-containing species. AB - A method for the separation of O-linked oligosaccharides into neutral, sialic acid-containing and sulfated species was applied to oligosaccharides released by alkaline borohydride from mucin glycopeptides from porcine small intestine. The released mixture of reduced oligosaccharides was applied to an anion exchange column, and the neutral oligosaccharides were collected as the unretarded fraction. A mixture of dimethyl sulfoxide and iodomethane was passed through the column to convert the sialic acid-containing oligosaccharides into methyl esters that were eluted and converted to methyl amides by methyl amine. Finally the sulfated oligosaccharide fraction was eluted with salt. The neutral and the derivatized sialic acid-containing oligosaccharides were analysed by gas chromatography-mass spectrometry after permethylation and the sulfated oligosaccharide fraction was analysed by high performance anion exchange chromatography. PMID- 7795417 TI - The asparagine-linked carbohydrate of honeybee venom hyaluronidase. AB - Hyaluronidase from the venom of the honeybee (Apis mellifera) has been purified by gelpermeation and cation exchange chromatography. Its asparagine-linked carbohydrate chains were released from tryptic glycopeptides with N-glycosidase A and reductively aminated with 2-aminopyridine. Separation of the fluorescent derivatives by size-fractionation and reversed-phase HPLC afforded eighteen fractions which were analysed by two-dimensional HPLC mapping combined with exoglycosidase digestions. The bulk of the N-linked glycans of hyaluronidase consisted of small oligosaccharides (Man1-3GlcNAc2), most of which were either alpha 1,3-monofucosylated or alpha 1,3-(alpha 1,6-)difucosylated at the innermost GlcNAc residue. High-mannose type structures constituted the minor fractions, together making up about 5% of the oligosaccharide pool from hyaluronidase. Four fractions, making up 8% of the N-linked glycans, contained the terminal trisaccharide GalNAc beta 1-4[Fuc alpha 1-3]GlcNAc beta 1- in beta 1,2-linkage to the core alpha 1,3-mannosyl residue. No evidence for the presence of O-glycans or sialic acids could be found. PMID- 7795416 TI - alpha 1-Acid glycoprotein binds human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein via N-linked glycans. AB - In the present study, we demonstrate a specific low-affinity interaction between recombinant precursor gp160 (rgp160) or surface unit gp120 (rgp120) of human immunodeficiency virus type 1 (HIV-1) and alpha 1-acid glycoprotein (AGP), a human glycoprotein displaying complex type N-glycans. Binding of rgp160/rgp120 to agarose-coupled AGP was dose-dependent, saturable, calcium-, pH- and temperature dependent. Binding was inhibited by soluble AGP, asialo-AGP, fetuin, beta-D GlcNAc47-BSA, alpha-D-Man20-BSA, mannan, complex-type asialo-agalacto tetraanternary precursor oligosaccharide from human AGP and oligomannose 9 from porcine thyroglobulin; fully deglycosylated AGP was not inhibitory. The three AGP glycoforms separated on immobilized ConA bound rgp160 to the same extent as did unfractionated AGP. These findings extend our previous results on the carbohydrate-binding properties of HIV-1 envelope (Env) glycoprotein in that they demonstrate the involvement of AGP glycan moieties in the binding to rgp160/rgp120. Preincubation of rgp160 with AGP or mannan significantly reduced its binding to monocyte-derived macrophages (MDM), suggesting that AGP may play a role in preventing binding of soluble or virus-bound Env glycoprotein to CD4+ monocytic cells. PMID- 7795418 TI - Characterization of the peptide-N4-(N-acetylglucosaminyl) asparagine amidase (PNGase Se) from Silene alba cells. AB - The peptide-N4-(N-acetylglucosaminyl) asparagine amidase (PNGase Se) earlier described [Lhernould S., Karamanos Y., Bourgerie S., Strecker G., Julien R., Morvan H. (1992) Glycoconjugate J 9:191-97] was partially purified from cultured Silene alba cells using affinity chromatography. The enzyme is active between pH 3.0 and 6.5, and is stable in the presence of moderate concentrations of several other protein unfolding chemicals, but is readily inactivated by SDS. Although the enzyme cleaves the carbohydrate from a variety of animal and plant glycopeptides, it does not hydrolyse the carbohydrate from most of the corresponding unfolded glycoproteins in otherwise comparable conditions. The substrate specificity of this plant PNGase supports the hypothesis that this enzyme could be at the origin of the production of 'unconjugated N-glycans' in a suspension medium of cultured Silene alba cells. PMID- 7795419 TI - Glycan structure of the S-layer glycoprotein of Bacillus sp. L420-91. AB - Preliminary taxonomic characterization of isolate L420-91 has revealed that this organism is closely related to the species Bacillus aneurinolyticus. The bacterium is covered by a squarely arranged crystalline surface layer composed of identical glycoprotein subunits with an apparent molecular mass in the range of 109 kDa. A total carbohydrate content of approximately 3.5% (wt/wt) was determined in the purified surface layer glycoprotein. Glycopeptides were obtained after exhaustive Pronase digestion and purification including gel filtration, ion exchange chromatography and HPLC. From the combined evidence of composition analysis. Smith degradation and nuclear magnetic resonance spectroscopy experiments we propose the following structure for the glycan chain of the surface layer glycoprotein: [formula: see text] PMID- 7795420 TI - The regulation of megakaryocytopoiesis. AB - The process of megakaryocytopoiesis begins with the commitment of a pluripotent hematopoietic stem cell to a differentiation pathway that culminates in the release of mature platelets into the circulation. A variety of megakaryocyte precursor cells have been identified after stem cell commitment has occurred and these may be recognized by their morphologic or immunophenotypic characteristics. Megakaryocytopoiesis is regulated by a number of cytokines with either stimulatory or inhibitory effects and by a variety of cell-cell interactions. Some factors potentiating platelet development promote the proliferation of megakaryocyte progenitor cells, while others result in their maturation. Thrombopoietin, a cytokine with specific megakaryocyte maturational activity recently has been identified as the c-Mpl ligand, and it will be evaluated as a therapeutic agent in the setting of thrombocytopenia due to impaired megakaryocytopoiesis. PMID- 7795421 TI - Maintaining quality in blood banking. AB - Regulation of transfusion or blood banking facilities has followed, rather than preceded the regulation of the pharmaceutical industry and today we find, in Europe and the United States, the basic regulations developed for the pharmaceutical industry being extended to blood transfusion centres (BTC)*. In this article we explore the role of voluntary accreditation or registration to quality systems standards such as ISO 9000 and discuss how these can be used to advantage and how these standards can provide a substantial base for meeting legislative requirements. In the UK there is also a voluntary accreditation procedure available for all clinical laboratories, known as Clinical Pathology Accreditation (CPA). Comparisons between ISO 9000, CPA and other standards are made. We also discuss how voluntary registration, particularly to ISO 9000 can provide an excellent basis for moving into more extensive and progressive Total Quality Management (TQM) programmes which in turn bring a variety of benefits, not least of which is increased staff involvement in your organisation. Experience of the route to quality through voluntary accreditation suggests that external assessment delivers new insights into the organisation that cannot easily be supplanted by internal audit. In Europe legislation relating to pharmaceuticals has steadily increased in scope and in detailed requirements from those set out in the 1965 Directive 65/65/EEC. The legislative framework has steadily increased, bringing plasma and plasma products as well as others such as radiopharmaceuticals, into the product licensing requirements. The progression of legislation seems unlikely to cease and it is debatable how long the Medicines Control Agency (MCA) and its Inspectorate will accept that BTCs can operate at a level which is different from that of the majority of pharmaceutical manufacturers. The change in emphasis in legislation particularly in Europe means that harm that is caused to a patient by a blood component will warrant redress. The degree of fault attributed to the producer will in part depend on whether they have met the best available standards at all stages in the preparation of the product. If a Transfusion Service can show that it's operation has external accreditation, particularly to an internationally recognised standard such as ISO 9000 and they can show that staff have been properly trained, that equipment is properly supplied and maintained and that the facility is appropriate to the work being carried out, then the liability that exists when something goes wrong will be reduced.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7795422 TI - Thalassemia major 1995: older patients, new therapies. AB - There have been many advances in supportive treatment used for beta-thalassemia major. Survival has increased substantially, and an increasing number of patients reach adolescence and adulthood. These older patients present new clinical challenges. Complications of transfusion, most commonly hepatitis C, are still a cause of mortality and morbidity. The achievement of optimal growth and development, including fertility, is an important goal of conservative management. Long-term survival has also been achieved with bone marrow transplantation. Assessment of growth, development and iron balance in the years after transplantation reveals residual problems requiring treatment despite cure of thalassemia. New therapies of beta-thalassemia are still being developed, both supportive and curative in nature. Supportive care improvements include oral chelation and methods to increase HbF production. Advances in curative modalities include use of new sources of stem cells, such as cord blood and fetal liver. In the future, gene therapy may allow for cure of the older patient without the mortality and morbidity of allogenic transplantation. Treatment of thalassemia major requires consideration of the available therapeutic options for each patient, and the risk/benefit ratio of a supportive versus curative approach. PMID- 7795424 TI - Leucodepletion of blood products by filtration. AB - The leucocytes present in red cell and platelet components have been implicated in several important immunological and infective complications of blood transfusion. Recent developments in blood filtration technology allow the production of leucodepleted blood products (residual leucocytes < 5 x 10(6) per transfused unit) in the laboratory or at the bedside with the potential to prevent these adverse effects. Quality assurance remains an important problem, particularly for bedside filtration. Prestorage filtration may have significant advantages for red cell and platelet production. There is strong clinical evidence that 3 log10 leucodepletion prevents or delays febrile reactions in patients receiving multiple red cell transfusions and can reduce cytomegalovirus transmission. Leucodepletion to prevent HLA alloimmunisation, platelet refractoriness and febrile reactions in patients receiving red cell and platelet support remains controversial. Transfused leucocytes induce 'immunosuppressive' changes in the recipient, but recent studies cast doubt on the association with cancer recurrence after surgery. However, leucodepleted blood may reduce the incidence of postoperative infection. Leucodepletion by filtration is expensive and there is a requirement for well-designed prospective clinical studies focusing on appropriate filtration technology (and alternatives), clinical outcome and cost-effectiveness. PMID- 7795423 TI - Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches. AB - During the past 6 decades, much attention has been devoted to understanding the uses, metabolism and hazards of iron in living systems. A great variety of heme and non-heme iron-containing enzymes have been characterized in nearly all forms of life. The existence of both ferrous and ferric ions in low- and high-spin configuration, as well as the ability of the metal to function over a wide range of redox potentials, contributes to its unique versatility. Not surprisingly, the singular attributes of iron that permit it to be so useful to life likewise render the metal dangerous to manipulate and to sequester. All vertebrate animals are prone to tissue damage from exposure to excess iron. In order to protect them from this threat, a complex system has evolved to contain and detoxify this metal. This is known as the iron withholding defense system, which mainly serves to scavenge toxic quantities of iron and also for depriving microbial and neoplastic invaders of iron essential for their growth. Since 1970, medical scientists have become increasingly aware of the problems involved in cellular iron homeostasis and of the disease states related to its malfunctioning. Scores of studies have reported that excessive iron in specific tissue sites is associated with development of infection, neoplasia, cardiomyopathy, arthropathy and a variety of endocrine and neurologic deficits. Accordingly, several research groups have attempted to develop chemical agents that might prevent and even eliminate deposits of excess iron. A few of these drugs now are in clinical use, e.g. deferiprone (L1). In the present review, we focus on recent developments in (i) selected aspects of the iron withholding defense system, and (ii) pharmacologic methods that can assist the iron-burdened patient. PMID- 7795425 TI - Spiritual emergency treatment of the newborn. PMID- 7795426 TI - Helping women with postpartum depression: midwives' expanding role. PMID- 7795427 TI - The health care system was in serious need of reform. PMID- 7795428 TI - Helping new mothers. PMID- 7795429 TI - Unplanned pregnancy. PMID- 7795430 TI - What is the best treatment for treating thrush? PMID- 7795431 TI - Birth story. PMID- 7795433 TI - Midwifery in Jamaica. PMID- 7795434 TI - Interview with Lea Rizack, CNM. Interview by Ina May Gaskin. PMID- 7795432 TI - Breastfeeding education needed. PMID- 7795435 TI - Treating hyperkinetic disorders in childhood. PMID- 7795436 TI - Do we need an Ofhealth? PMID- 7795438 TI - Integrating pharmacy fully into the primary care team. PMID- 7795439 TI - Chemoprophylaxis in tuberculosis and HIV infection. PMID- 7795437 TI - Hepatitis C and haemophilia. PMID- 7795440 TI - Colleges call for safe drink limits to stay. PMID- 7795441 TI - Pensioners win test case over care cuts. PMID- 7795442 TI - Dutch report advises prescribing heroin for misusers. PMID- 7795443 TI - Medical records need better management. PMID- 7795444 TI - Spanish abortion reform faces opposition. PMID- 7795445 TI - South African GPs consider health insurance. PMID- 7795446 TI - Hardliners and liberals unite on drugs policy. PMID- 7795447 TI - Reasons for non-uptake of measles, mumps, and rubella catch up immunisation in a measles epidemic and side effects of the vaccine. AB - OBJECTIVE: To investigate the reasons for poor uptake of immunisation (non immunisation) and the possible side effects of measles, mumps, and rubella vaccine in a catch up immunisation campaign during a community outbreak of measles. DESIGN: Descriptive study of reasons for non-immunisation and retrospective cohort study of side effects of the vaccine. SETTING: Secondary schools in South Glamorgan. SUBJECTS: Random cluster sample of the parents of 500 children targeted but not immunised and a randomised sample of 2866 of the children targeted. MAIN OUTCOME MEASURES: Reasons for non-immunisation; symptoms among immunised and non-immunised children. RESULTS: Immunisation coverage of the campaign was only 43.4% (7633/17,595). The practical problems experienced included non-return of consent forms (6698/17,595), refusal of immunisation (2061/10,897 forms returned), and absence from school on day of immunisation (1203/8836 children with consent for immunisation). The most common reasons cited for non-immunisation were previous measles infection (145/232), previous immunisation against measles (78/232), and concern about side effects (55/232). Symptoms were equally common among immunised and non-immunised subjects. However, significantly more immunised boys than non-immunised boys reported fever (relative risk 2.31 (95% confidence interval 1.36 to 3.93)), rash (2.00 (1.10 to 3.64), joint symptoms (1.58; 1.05 to 2.38), and headache (1.31 (1.04 to 1.65)). CONCLUSIONS: Many of the objections raised by parents could be overcome by emphasising that primary immunisation does not necessarily confer immunity and that diagnosis of measles is unreliable. Measles, mumps, and rubella vaccine is safe in children aged 11-15. PMID- 7795450 TI - ABO and Rh blood groups in patients with cholelithiasis and carcinoma of the gall bladder. PMID- 7795448 TI - Serum cholesterol concentrations in parasuicide. AB - OBJECTIVE: To evaluate whether people who have committed parasuicide have low serum cholesterol concentrations. DESIGN: Results of blood tests in subjects admitted to hospital for parasuicide compared with those of a control group of non-suicidal subjects; comparison in subgroup of parasuicide subjects of two sets of blood test results (one set from admission for parasuicide and the other from admission for some other illness). SETTING: General hospital, Ferrara, Italy. SUBJECTS: 331 parasuicide subjects aged 44 (SD 21) years (109 with two sets of blood test results) and 331 controls. MAIN OUTCOME MEASURES: Serum cholesterol concentrations and possible association with parasuicide, considering sex, violence of method of parasuicide, and underlying psychiatric disorder. RESULTS: Lower serum cholesterol concentrations (4.96 (SD 1.16) mmol/l) were found in the parasuicide subjects than in the controls (5.43 (1.30); P < 0.001), regardless of sex and degree of violence of parasuicide method. Both men and women with two sets of blood test results had lower cholesterol concentrations after parasuicide. Linear regression analysis showed that the difference in cholesterol concentrations was significantly related to the length of time between the taking of the two sets of blood samples. CONCLUSION: The study showed low cholesterol concentrations after parasuicide. This finding agrees with previous studies, which suggest an association between low cholesterol concentration and suicide. PMID- 7795449 TI - Strategies for dealing with problems associated with use of services for HIV infection and AIDS out of region: views of providers and users. AB - OBJECTIVES: To identify reasons why people with HIV infection and AIDS living within the former South West Thames Regional Health Authority use HIV and AIDS services outside the region, and to identify strategies for dealing with the problems associated with such use. DESIGN: Qualitative study consisting of interviews with individual subjects and focus groups. SETTING: Providers of services for patients with HIV infection and AIDS in South West Thames, central London, and Brighton. Users of such services resident in South West Thames. SUBJECTS: Thirty four South West Thames residents with HIV infection and AIDS who use or used services outside the former region; and 70 providers of services within and beyond South West Thames. RESULTS: Principal reasons for use of services out of the region were accessibility (15) and negative appraisals of local services (14). Three main strategies for dealing with the problems of such use were suggested by providers. These entailed introducing users of services outside the region to services in their locality (16); sharing the responsibility for care between providers in specialist centres and in the person's locality (10); and involving the person's general practitioner in their care (12). These strategies were deemed acceptable by 29, 30, and 20 service users respectively. CONCLUSION: The reasons underlying use of services for patients with HIV infection and AIDS outside the region offer suggestions for developing services in areas with a high incidence of such use. The suggestions advanced by service providers offer an acceptable framework for dealing with the problems. PMID- 7795451 TI - GR106642X: a new, non-ozone depleting propellant for inhalers. PMID- 7795452 TI - Contraceptive services for teenagers: do we need family planning clinics? AB - OBJECTIVE: To determine whether the effectiveness of contraceptive services for teenagers is related to the balance of service provision between general practitioners and specialist family planning services. DESIGN: Cross sectional study with routinely collected data from family planning clinics and family health services authorities and published data on births and abortions. SETTING: Eight health districts in the former Oxford region. SUBJECTS: Girls aged under 16 and women aged 16-19 who attended a contraceptive service during 1991-2 or who gave birth or had an abortion during 1990-2. MAIN OUTCOME MEASURES: Attenders at family planning clinics as a percentage of all users of contraceptive services. The conception rate:uptake of contraceptive services ratio was used as a measure of effectiveness. RESULTS: In comparisons between districts the percentage of all users of contraceptive services who attended a clinic varied from 38% (95% confidence interval 28% to 48%) to 79% (72% to 86%) among 13-15 year olds and from 14% (12% to 15%) to 44% (42% to 46%) among women aged 16-19 years. The conception rate: uptake of contraceptive services ratio varied twofold in the older age group and more than threefold in the younger age group. It was lowest in districts where clinic attenders comprised a large percentage of all users of contraceptive services. CONCLUSION: Contraceptive services for teenagers may be more effective in districts where clinics play a large part in delivering the service, particularly for girls aged under 16. PMID- 7795453 TI - Pregnant teenagers' knowledge and use of emergency contraception. PMID- 7795454 TI - Reflex sympathetic dystrophy. PMID- 7795455 TI - Lesson of the week. Reflex sympathetic dystrophy in children. PMID- 7795457 TI - Is there convergence between Britain and the United States in the organisation of health services?. Interview by Penny Newman. AB - Is the organisation of health care in Britain becoming similar to that in the United States? Since the introduction of the internal market radical change has gripped the NHS. In the United States, despite the failure to implement coherent health care reform, a health care revolution is under way, driven by cost containment. At the centre of these changes is managed competition. Alain Enthoven, Marriner S Eccles professor of public and private management at Stanford University, has been the principal proponent of managed competition in both countries. His writings inspired the NHS reforms in 1989 and President Clinton's advisers to adopt managed competition in 1994, though ultimately he became opposed to the Clinton plan. In this interview with Penny Newman he redefines managed competition, explores the similarities and differences that have arisen between Britain and the United States, and describes recent trends in the United States, many of which are being mirrored in Britain. He illustrates a degree of convergence between the two countries. This was unthinkable 10 years ago when comparing the fee for service system in the United States with the NHS. PMID- 7795456 TI - ABC of medical computing. An introduction to computing in medical practice. PMID- 7795458 TI - Dilemmas in rationing health care services: the case for implicit rationing. AB - With tension between the demand for health services and the cost of providing them, rationing is increasingly evident in all medical systems. Until recently, rationing was primarily through the ability to pay or achieved implicitly by doctors working within fixed budgets. Such forms of rationing are commonly alleged to be inequitable and inefficient and explicit rationing is advocated as more appropriate. Utilisation management in the United States and quasi-markets separating purchasing from provision in the United Kingdom are seen as ways of using resources more efficiently and are increasingly explicit. There is also advocacy to ration explicitly at the point of service. Mechanic reviews the implications of these developments and explains why explicit approaches are likely to focus conflict and dissatisfaction and be politically unstable. Explicit rationing is unlikely to be as equitable as its proponents argue and is likely to make dissatisfaction and perceived deprivation more salient. Despite its limitations, implicit rationing at the point of service is more sensitive to the complexity of medical decisions and the needs and personal and cultural preferences of patients. All systems use a mix of rationing devices, but the clinical allocation of services should substantially depend on the discretion of professionals informed by practice guidelines, outcomes research, and other informational aids. PMID- 7795460 TI - Remembrance of conversations past: oral advance statements about medical treatment. AB - Polls show increasing public interest in advance statements or directives about medical treatment ("living wills") but that few people, apart from Jehovah's Witnesses, carry such documents. Patients' firm, witnessed oral decisions are often sufficient to aid clinical decision making but should still be recorded in medical notes. Without documentation, dilemmas arise when others claim to know patients' views on the basis of past unrecorded conversations and demand withdrawal of treatment when patients are not terminally ill and cannot speak for themselves. Legal and ethical considerations oblige doctors to act in the best interests of an incapacitated patient; these considerations are now formally defined in draft legislation as including consideration of the patient's past wishes. The practicalities of ascertaining the strength and validity of such wishes from conversations reported second hand are complex. The paucity of legal and ethical guidance on reported oral advance statements makes debate imperative and renders the alternative of having designated surrogate decision makers increasingly attractive. PMID- 7795459 TI - Financial ties as part of informed consent to postmarketing research. Attitudes of American doctors and patients. AB - Postmarketing research, often called phase IV trials, is intended to familiarise doctors and patients with newly approved drugs. La Puma and colleagues, in Chicago, studied doctors' and patients' attitudes to whether doctors should receive payment for taking part in such research. We asked for commentaries on their findings from four ethical experts, who put the study in a British context, present the views of patients, and examine some methodological assumptions. PMID- 7795461 TI - Diagnosis and treatment of Parkinson's disease. Anosmia is a common finding. PMID- 7795462 TI - Diagnosis and treatment of Parkinson's disease. Anticholinergic drugs are not contraindicated after iridotomy. PMID- 7795463 TI - Alcoholism and rising mortality in the Russian Federation. PMID- 7795464 TI - Improving the detection of glaucoma. Intraocular pressure of greater than 21 mm Hg is an indication to refer. PMID- 7795465 TI - Lipid lowering dietary advice. PMID- 7795466 TI - Magnesium in acute myocardial infarction. PMID- 7795467 TI - Mutual trust. PMID- 7795468 TI - Practising public health in primary care is easier said than done. PMID- 7795469 TI - Professional negligence. Candid disclosure is right. PMID- 7795470 TI - Professional negligence. Doctors may make mistakes that are less obvious than lawyers' mistakes. PMID- 7795471 TI - Ethics and economics of health care. Prognosis, a traditional alternative to futility. PMID- 7795472 TI - Ethics and economics of health care. British medicine has lessons for North American medicine. PMID- 7795473 TI - Incidence of diabetes in children. PMID- 7795474 TI - Specialists in the United States. PMID- 7795475 TI - Coping with psoriasis. PMID- 7795476 TI - Malaria prophylaxis. PMID- 7795477 TI - Unified training grade. Purchasers cannot put the cart before the horse. PMID- 7795478 TI - Vitamin E deficiency. PMID- 7795479 TI - Deprivation payments to general practitioners. PMID- 7795480 TI - Hospital doctors' work. PMID- 7795482 TI - BMJ on the internet. Neuroscience on the internet. PMID- 7795481 TI - Unified training grade. Vocational training for GPs should be community based. PMID- 7795483 TI - Hormonal effect on the osmotic, electrolyte and nitrogen balance in terrestrial Amphibia. AB - Two main hormones regulate water balance in amphibian. First, mesotocin (MT) acting as a diuretic agent, and second arginine vasotocin (AVT) being an anti diuretic hormone. In addition, prolactin (PRL), aldosterone, corticosterone, angiotensin II and atriunatriuretic hormones, play a role too in regulating water and ion balance. The hormones affect the epidermis and bladder permeability to water and ions as well as the kidney through the control of the glomerular filtration rate (GFR). The main questions concern the presence and action of these hormones during the amphibian's life history. Are they present in both larval and adult stages? Are these hormones being synthesized in both aquatic and terrestrial adult phases? Under what circumstances are they being stored or released? Would the target organs (epidermis, bladder, kidney) respond in a similar way during all periods? The problem is the fact that under most circumstances an amphibian while in an aquatic environment responds physiologically differently than when on land. Only partial information concerning hormone presence, release and control of water balance is available at the moment, and even that is fragmentary and based on only a very small number of amphibian species. PMID- 7795484 TI - Quantitative analysis of metamorphosis induced by L-glutamine in embryos of the sea urchin, Hemicentrotus pulcherrimus. AB - Metamorphosis of the sea urchin, Hemicentrotus pulcherrimus, can be induced by L glutamine as reported previously for Pseudocentrotus depressus [15]. To analyze more precisely the process of metamorphosis induced by L-glutamine, the development of the echinus rudiment (ER) was classified into six stages. The stage at which the larvae underwent the normal metamorphosis by glutamine treatment was confirmed. The time of the glutamine treatment required for metamorphosis (the eversion of ER) was over 10 hr but treatment for more than 25 hr tended to decrease the number of metamorphosed larvae, although the larval arms had mostly been resorbed. The time of glutamine treatment to induce the metamorphosis, depended on the development of ER; more time was required for the younger larvae and less time for the older. The high mitotic activities observed in the cells of the ciliary bands were markedly decreased in the glutamine treated larvae to metamorphose. These findings suggested that a degenerative process of metamorphosis including cell death is induced by L-glutamine. PMID- 7795485 TI - Amphibian amplexus in microgravity. AB - We report here on the amplectic behavior of the Japanese treefrog (Hyla japonica) in microgravity. Treefrogs were exposed to 35 cycles of altered gravity, including approximately 1.5 sec of G < 0.1 every 3 min and 15 sec, on the FreeFall "G.0" ride at Space World amusement park in Kitakyushu, Japan. During this period a pair of frogs spontaneously entered and maintained amplexus for 1 hr 20 min, before being removed from the ride. In freefall, the pair extended their hindlimbs in the characteristic posture of treefrogs in microgravity. This is the first report of a vertebrate entering and sustaining a copulatory or amplectic posture under gravitational extremes, including true freefall. These observations bode well for the potential of anurans to breed in microgravity and to be used for biological research in space. PMID- 7795486 TI - Numbers of olfactory receptor cells and fine structure of olfactory nerves in various birds. AB - The numbers of olfactory receptor cells from electron micrographs in various species of birds were counted and the fine structure of their olfactory nerves was observed using electron micrographs. The birds were domestic ducks, a slay backed gull, quails, budgerigars and bengalees. Data from pigeons obtained from a previous study were also included for comparison. The approximate numbers of olfactory cells on each side were 5,800,000 in the duck, 2,700,000 in the gull, 570,000 in the quail, 130,000 in the budgerigar, and 110,000 in the bengalee. From a cross section of an olfactory nerve, the nerve was observed to be divided roughly into several fascicles by perineurium. Each fascicle was composed of many small bundles which were surrounded by endoneurium. Each small bundle was separated into several divisions by mesaxon which originated from Schwann cells. In the anterior part of the nerve, the number of axons surrounded by mesaxon ranged between one and several dozen. The number in the middle part was much larger than in the anterior part. In the posterior part the number decreased again. The diameter of an axon was 0.21-0.26 microns on average. The axon contained neurotubules, neurofilaments, mitochondria and axonal smooth ER. The fine structure of the olfactory nerve and the numbers of olfactory cells in these birds are discussed and compared with those of other vertebrates. PMID- 7795487 TI - Structure, function and biosynthesis of sperm-activating peptides and fucose sulfate glycoconjugate in the extracellular coat of sea urchin eggs. AB - A decapeptide (GFDLNGGGVG) isolated from the solubilized jelly layer of the sea urchin Hemicentrotus pulcherrimus stimulates the respiration and motility of H. pulcherrimus spermatozoa and, in addition, produces a number of biological effects on H. pulcherrimus spermatozoa including increases in cAMP and cGMP levels, activation of a Na+/H+ exchange system, and increases in intracellular pH (pHi) and [Ca2+] ([Ca2+]i). The peptide activates the metabolism of endogenous phosphatidylcholine and promotes the acrosome reaction as a specific co-factor of a major acrosome reaction-inducing substance, fucose sulfate glycoconjugate. The peptide also induces an electrophoretic mobility change in the guanylate cyclase of the sperm plasma membrane with concomitant dephosphorylation and inactivation of the enzyme. Seventy-four peptides producing similar biological effects, named sperm-activating peptide (SAP), have since been purified from the solubilized jelly layer of seventeen species of sea urchins distributed over five taxonomic orders. These peptides show essentially the same biological effects on sea urchin spermatozoa although their activity and structures are specific at the ordinal level. Equilibrium binding experiments using a radioiodinated SAP-I analogue [GGGY(125I)GFDLNGGGVG] to H. pulcherrimus spermatozoa suggests the presence of two classes of receptors (high affinity and low affinity) specific for SAP-I binding. Based on the Kd values and EC50's for SAP-I's biological activity, we presume that the high affinity receptor is associated with respiration stimulating activity and elevations in pHi, while the low affinity receptor is coupled to elevations in cGMP and [Ca2+]i. The radioiodinated SAP-I analogue crosslinks to a 71 kDa protein which contains a single membrane-spanning domain at almost near C-terminus. A SAP-I precursor which is synthesized in the accessory cells contains five SAP-I and seven SAP-I-like decapeptides, each separated by a single lysine residue. PMID- 7795488 TI - The mutant gene product of a Tetrahymena cell-division-arrest mutant cdaA is localized in the accessory structure of specialized basal body close to the division furrow. AB - A division arrest mutant, cdaA, of Tetrahymena thermophila is known to have a temperature sensitive-defect in the determination of the division plane, and its gene product had been shown to be a protein designated as p85 (Mr = 85,000; pI = 4.7). Here the localization of p85 was shown to be the accessary structure of specialized basal body close to the division furrow by immunoelectron microscopy using anti-p85 antiserum. PMID- 7795489 TI - Intracellular alkalinization enhances inward rectifier K+ current in retinal horizontal cells of catfish. AB - Isolated cone-driven horizontal cells dissociated from catfish retina were voltage-clamped using the whole-cell patch-clamp technique. The effects of acidification and alkalinization on an anomalous type, inwardly-rectifying K+ current (IRK+) were investigated. The magnitude of IRK+ was enhanced by raising the intracellular pH above 7.4, however, in contrast, intracellular acidification had little effect on this current. The range over which intracellular pH ([pH]i) modulates IRK+ is different from that for modulation of a sustained high-voltage activated calcium current in these same cells and also for proton-sensitive, inward rectifier currents in starfish oocytes, skeletal muscle and heart myocytes. PMID- 7795490 TI - Up- and down-modulation of a cloned Aplysia K+ channel (AKv1.1a) by the activators of protein kinase C. AB - Modulation of a cloned Aplysia K+ channel, AKv1.1a, by protein kinase C (PKC) activators was examined in Xenopus oocytes expression system. Following the application of phorbol esters (phorbol 12-myristate 13-acetate, PMA; phorbol 12,13-dibutyrate, PDBu), or a diacylgrycerol analogue (1-oleoyl-2-acetyl-sn glycerol, OAG), the fast inactivation of the AKv1.1a became slower and the peak current increased (up-modulation). However, the effect was transient. The expressed current was decreased even below control level about 15 to 20 min after the treatment (down-modulation). Both effects by PMA was blocked by the kinase inhibitor, H7, suggesting that phosphorylation by PKC is involved. The amino acid sequence of AKv1.1a contains three putative phosphorylation sites by PKC (Ser24, Thr345, Ser349). We tested their contributions to the PMA-induced modulation by site-directed mutagenesis. The results suggest that the up-modulation by PKC activators is due to the inhibition of the fast inactivation by the amino terminal domain (N-type inactivation), thereby increase the time the channels are conductive. Phosphorylation of Ser24 may enhance the PKC-induced down-modulation, while phosphorylation of Thr345 may inhibit the down-modulation. By contrast, mutation of Ser349 did not affect the modulation. The N-type inactivation were not indispensable for the down-modulation because the amino-terminal deletion mutant also showed some down-modulation although its onset was quite slow. Thus, the down-modulation of AKv1.1a may be heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795491 TI - Quinine-HCl-induced modification of receptor potentials for taste stimuli in frog taste cells. AB - After frog taste cells were adapted to 1 mM quinine-HCl (Q-HCl) for 10 sec, modification of receptor potentials in the taste cells induced by salt, acid, sugar and bitter stimuli was studied with microelectrodes. The phasic component of receptor potentials induced by 0.1 M NaCl, KCl, NH4Cl and MgCl2 was enhanced following adaptation to Q-HCl. The rate of rise of receptor potentials in response to the salts was increased after Q-HCl adaptation. The amplitude and the rate of rise of receptor potentials induced by 1 mM acetic acid were larger after Q-HCl adaptation than after water adaptation. The amplitude of phasic component and rate of rise of receptor potentials for 0.5 M sucrose after Q-HCl were the same as those after water. The amplitudes of tonic receptor potentials for 1 mM Q H2SO4, brucine and picric acid after Q-HCl adaptation were the same as those after 1 mM NaCl adaptation. Correlation coefficient between taste cell responses induced by 1 mM Q-HCl and 1 mM Q-H2SO4 was very high, but those between 1 mM Q HCl and 1 mM brucine responses and between 1 mM Q-HCl and 1 mM picric acid responses were low. This indicates that Q-HCl and Q-H2SO4 bind to the same receptor site, but brucine and picric acid bind to different receptor sites to which Q-HCl does not bind. PMID- 7795493 TI - Identification of peanut agglutinin-binding glycoproteins on lizard lymphocytes. AB - The expression of PNA-binding glycoproteins on lizard lymphocytes was investigated by studying the reactivity of FITC-PNA towards lizard lymphocytes obtained from the different lymphoid organs. Direct immunofluorescence assays have demonstrated that the majority of lizard thymocytes (70%) and only a fraction of lymphocytes in the spleen, peripheral blood and bone marrow were PNA positive. This positivity was selectively inhibited by galactose as well as lactose, indicating the specificity of binding. Putative PNA receptors were purified from lizard thymocytes and splenocytes by affinity chromatography on a PNA-Sepharose 4B column and resulted in fractions enriched 1,792-fold and 3,141 fold for the PNA-binding component expressed on lizard thymocytes and splenocytes, respectively. Analysis on reducing and non-reducing SDS-PAGE revealed that both thymic and splenic PNA-binding glycoproteins migrated as a single component of 35 KDa, with no evidence for the association into higher multimers in both tissues. Analyses for amino acid and carbohydrate compositions indicated that the thymic and splenic glycoproteins have similar amino acid composition and differed in the content of neutral and amino-sugars as well as sialic acid. The content of the latter residue was relatively higher in the splenic form of the receptor compared to its thymic counterpart, and was inversely correlated with the content of galactosyl residues in both forms of the receptor. The functional significance of PNA-binding glycoproteins during vertebrate evolution is discussed. PMID- 7795494 TI - Occurrence of a latent serine protease in the follicular fluid of porcine ovary. AB - Porcine ovary follicular fluid contains a latent form of a protease which is activatable with trypsin. The active enzyme hydrolyzed peptide 4-methylcoumaryl-7 amide (MCA) substrates with a preference for the Arg-MCA bond. The enzyme was strongly inhibited by diisopropylfluorophosphate, aprotinin, leupeptin and antipain, but not by soybean trypsin inhibitor. The apparent molecular weight of the enzyme was approximately 630,000 as estimated by gel filtration. No significant difference in molecular size was seen between the inactive precursor and trypsin-activated enzyme. The results suggest that the present enzyme is a novel type of serine protease. PMID- 7795492 TI - A proteinous factor mediating intercellular communication during the transition of Dictyostelium cells from growth to differentiation. AB - In general, cell differentiation and proliferation are mutually exclusive. Transition of the cellular slime mold Dictyostelium discoideum from growth to differentiation is triggered mainly by a secreted factor(s) in addition to nutritional deprivation. To purify and identify the factor required for the growth/differentiation transition, a new assay system was designed. Under low nutrient conditions, cells could grow to multiply, but never developed. The cellular development including aggregation, however, was induced by the addition of conditioned medium (CM) in which growing or starving Dictyostelium cells had been cultured. The CM inhibited the synthesis of nuclear DNA and induced the cells to acquire chemotactic competence to cAMP, thus suggesting the presence of a secreted factor(s) required for growth/differentiation transition in the CM. The active factor(s) in CM (referred to as CMF450; conditioned medium factor) was found to be sensitive to heat and have a large molecular size. The CMF450 was purified using FPLC through a gel filtration column, and was identified to be a proteinous macromolecule of Mr 450 kDa, which was mainly composed of 94 kDa, 79 kDa, and 49 kDa subunits under a native condition. PMID- 7795495 TI - Effect of hypoglycemic stress on the pars intermedia of the mouse pituitary gland: an ultrastructural analysis. AB - The present study was made to clarify the relationship between functions of the pars intermedia of the mouse pituitary gland and hypoglycemic stress. Morphometrical analysis of the ultrastructures of the pars intermedia cells showed (1) a rise in the percentage volume of rough endoplasmic reticulum (r-ER) indicative of an increase in protein synthesis, (2) an increase in the number of Golgi granules per unit Golgi area showing an induction of granule-forming activity and (3) a decrease in the numerical density of secretory granules reflecting a release of the secretory granules. These findings suggest that hypoglycemic stress induced by daily treatment with insulin or restriction of food intake was able to elicit heightened secretory activity of the pars intermedia cells of the mouse pituitary gland. However, acute hypoglycemic stress induced by food deprivation did not cytologically affect the pars intermedia. These observations suggest that repeated hypoglycemic stress, rather than acute hypoglycemic stress, may be a natural physiological stimulus of the pars intermedia of the mouse pituitary gland. PMID- 7795496 TI - Addiction research in a wealthy nation: is there an expanding German research presence? PMID- 7795497 TI - The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. AB - The Severity of Dependence Scale (SDS) was devised to provide a short, easily administered scale which can be used to measure the degree of dependence experienced by users of different types of drugs. The SDS contains five items, all of which are explicitly concerned with psychological components of dependence. These items are specifically concerned with impaired control over drug taking and with preoccupation and anxieties about drug use. The SDS was given to five samples of drug users in London and Sydney. The samples comprised users of heroin and users of cocaine in London, and users of amphetamines and methadone maintenance patients in Sydney. The SDS satisfies a number of criteria which indicate its suitability as a measure of dependence. All SDS items load significantly with a single factor, and the total SDS score was extremely highly correlated with the single factor score. The SDS score is related to behavioural patterns of drug taking that are, in themselves, indicators of dependence, such as dose, frequency of use, duration of use, daily use and degree of contact with other drug users; it also shows criterion validity in that drug users who have sought treatment at specialist and non-specialist agencies for drug problems have higher SDS scores than non-treatment samples. The psychometric properties of the scale were good in all five samples, despite being applied to primary users of different classes of drug, using different recruitment procedures in different cities in different countries. PMID- 7795498 TI - Alcohol abuse and dependence: consistency in reporting of symptoms over ten years. AB - The present study assesses the stability of the diagnosis of alcoholism among a sample of St Louis, USA Epidemiological Catchment Area Study participants. The Diagnostic Interview Schedule was used at Time 1 and the Composite International Diagnostic Interview--Substance Abuse Module was used at 10-year follow-up. Alcohol abuse and dependence were diagnosed using DSM-III criteria. Kappa values and Yule's statistics for agreement in diagnoses, criterion groups and individual symptoms are reported. Fair to good measurement of agreement was shown for any diagnosis of alcohol abuse or dependence versus no diagnosis. The criterion group for "impairment in social or occupational functioning" showed the highest agreement of the three criterion groups studied. Agreement was lower for individual symptoms of alcoholism. Incident cases accounted for some of the inconsistency in responses over 10 years. Other types of inconsistency found were changing response from yes to no, changing response from no to yes but not meeting the definition of an incident case, and misstating age of onset of symptoms. Mean per cent inconsistency across all symptoms was 11.4%. Further research regarding reasons for inconsistencies is needed. PMID- 7795499 TI - Withdrawal and dependency symptoms among adolescent alcohol and drug abusers. AB - Due to differences in duration, intensity and topography of alcohol and drug use patterns, the withdrawal and dependency symptoms of adolescent substance abusers may differ from those of adult substance abusers. To explore these potential differences, 166 adolescents recruited from inpatient alcohol and drug treatment programs in the USA were assessed for alcohol and other drug withdrawal and dependency symptoms. Teens were administered the Customary Drinking and Drug Use Record following 2 weeks of abstinence and evaluated for recent (< 3 months) DSM III-R psychoactive substance withdrawal and dependency symptoms. Adolescents were all multiple substance users with a life-time average of 4.27 drugs used in addition to alcohol. Amphetamines were the most frequently used drug (50% of sample) and the most prevalent withdrawal symptoms were those associated with central stimulant use. However, the number of different withdrawal symptoms (M = 11.27) was greater than expected for uncomplicated stimulant withdrawal or withdrawal from any single substance. On average, participants reported dependency symptoms more than DSM-III-R criteria for the diagnosis of alcohol dependency (M = 3.30), as well as dependency on their two most frequently used drugs. Heavy alcohol and cigarette use were found to exacerbate withdrawal symptoms of other drugs. These findings highlight the importance of assessing adolescent substance abusers for withdrawal from and dependency on multiple substances. PMID- 7795500 TI - Factor analysis of alcohol abuse and dependence symptom items in the 1988 National Health Interview Survey. AB - The findings presented in this report are of general interest for the development of survey instruments for alcohol use disorders. They show which items represent the same dimension of alcohol problems when presented to respondents in a general population survey setting. The note determines the major dimensions underlying the complete set of 41 symptom items in the 1988 National Health Interview Survey, relates the item sets of the DSM- and ICD-criteria to these dimensions, and studies the measurement characteristics of items not used for DSM- or ICD criteria. PMID- 7795501 TI - The role of peer affiliations, social, family and individual factors in continuities in cigarette smoking between childhood and adolescence. AB - The continuity between early smoking experimentation and smoking at age 16 years was analysed for a birth cohort of New Zealand children. This analysis suggested that when due allowance was made for errors in reports of smoking behaviours, there was evidence of relatively strong continuity (r = 0.60) between early smoking experimentation and cigarette smoking at age 16 years. Further analysis suggested that the continuities between early smoking experimentation and later smoking arose from three pathways that linked early smoking experimentation to later smoking. First there was evidence to suggest that children who engaged in early smoking experimentation tended to affiliate with adolescent peer groups whose members smoked. In turn, these peer group affiliations reinforced pre existing tendencies to cigarette smoking. Secondly, a small component of the apparent continuity between early smoking experimentation and later smoking arose because of common social, individual and contextual factors that were associated with both smoking experimentation and later smoking. Finally, there was evidence of moderate direct continuity in cigarette smoking behaviour over time. The implications of these findings for the development of smoking prevention programmes are discussed and it is concluded that effective programmes need to be embedded in a developmental approach which attempts to reduce both early smoking experimentation and the effects of peer pressure in adolescence on the development of cigarette smoking. PMID- 7795502 TI - The effects of expectancy and alcohol on cognitive-motor performance. AB - Previous studies have found equivocal evidence for expectancy effects on cognitive-motor performance. The effects of expectancy and alcohol on a dual tracking and reaction-time task analogous to some driving skills, and on choice reaction-time, were studied in a balanced-placebo design (n = 90). A dose of alcohol achieving 80 mg/100 ml (high dose) had large effects on both tasks, but a low dose (40 mg/100 ml) had no significant effects. Expecting alcohol led to subjects who received the high dose performing significantly better on the primary tracking task than subjects expecting placebo (but also receiving the high alcohol dose). By contrast, on a secondary reaction-time task, subjects who had received placebo performed worse 100-130 minutes after drinking, if they had expected alcohol. All groups felt more drunk than baseline and expecting alcohol made subjects feel more able to perform, whatever drink they had received. The implications of these findings for the nature of expectancy effects on performance and the relationship between expectations and strategy are discussed. PMID- 7795503 TI - New beverages, new drinking contexts? Signs of modernization in Finnish drinking habits from 1984 to 1992, compared with trends in the European Community. AB - The dynamics of change in drinking patterns is discussed using the data from the drinking habits surveys conducted in Finland in 1984 and 1992. The results are compared with a respective analysis on the EU countries from 1988 by Hupkens, Knibbe & Drop (1993). The analysis is based on changes in beverage preferences. In the Finnish case, both wine and mild beer appear as new beverages, gaining popularity in the late 1980s. For beer, both the elites and the population at large were involved in that process. For wine, the interest in the new beverage was stronger among the elites. There were notable gender differences in adopting the new beverage. Some of the differences were related to the older cultural patterns of wine as a woman's drink and beer as a male beverage. The results also point to difficulties in analysing the dynamics of change on the basis of cross sectional data, as was done in the earlier analysis on the EC countries. The Finnish data shows that even the inter-group dynamics of drinking patterns may change over a relatively short period of time. PMID- 7795504 TI - Alcohol abuse and suicide: a 40-year prospective study of Norwegian conscripts. AB - Suicide mortality among alcohol abusers and the prevalence of alcohol abusers among suicides were assessed in a 40-year follow-up study of 40,000 Norwegian military conscripts. Alcohol abuse was operationalized as either admission to alcohol treatment clinic, alcohol related cause of death, or both. The relative risk of suicide among alcohol abusers was estimated to 6.9. The relative risk of committing suicide among alcohol abusers appeared to be higher in middle age (more than 40 years) than in younger age groups (RR = 12.8 and 4.5, respectively). The life-time risk of suicide, i.e. before the age of 60 years, was estimated to 0.63% for those not categorized as alcohol abusers and 4.76% for those categorized as alcohol abusers. PMID- 7795505 TI - Alcoholism in Brazil--the role of personality and susceptibility to stress. AB - One hundred alcohol-dependent Brazilian males were investigated in relation to variables dealing with the course of alcoholism, family history and behaviour. Seven of the most representative were standardized and then subjected to a factor analysis. The factors thus obtained were afterwards included in a cluster analysis, which identified three groups of alcoholics. Two of these groups agree with those established on recent previous classifications, while the third revealed a characteristic not identified in these typologies: lower levels of stress. Other distinctive features were lower scores of harm avoidance and higher proportion of alcoholic relatives. In relation to other conditions these subjects presented intermediary values, suggesting that they may constitute an intermediate between the two other, polar types. It will be important to verify if these results are confirmed in populations with biological and cultural characteristics different from the Brazilian one. PMID- 7795506 TI - Social relationships and abstinence from cocaine in an American treatment sample. AB - In an extension of earlier work relating social-relationship variables to post treatment abstinence from abused drugs, 104 cocaine users were studied for 6 months after completing drug treatment. Social-relationship variables included social integration, perceived support and social-network cocaine use. The effects of social relationships on cocaine abstinence tended to be conditional on race. Greater social integration predicted abstinence for Caucasian Ss (n = 54), but not African-Americans (n = 50). Similar results occurred for perceived support. Social network drug-use data also showed race differences: the absence of current cocaine users and the presence of former users predicted abstinence only for Caucasians. Interpretation of these findings is complicated by the relationship we observed between race and route of cocaine administration, with African American Ss far more likely than Caucasians to be crack smokers or injection users as compared to intranasal users. The effects of race could not be disentangled from the effects of route. Future studies of social relationships and cocaine abstinence should focus on identifying social factors that are protective for African-Americans and for smokers/injectors. Such studies are critical precursors to designing successful social-support interventions. PMID- 7795508 TI - Recognition performance of subjects with color-vision deficiencies on a polychromatic sonar screen for ship navigation. AB - To facilitate differentiation between objects that are approaching, stationary, and moving away, these objects are represented in different colors on the screens of sonar locating devices used in ship navigation. Yellow represents stationary objects, and represents approaching objects, and green represents those objects moving away. A total of 46 subjects with normal color vision and 184 individuals with color-vision deficiencies, among them 29 deuteranopic, 100 deuteranomalous, 21 protanopic and 34 protanomalous individuals, were investigated for their ability to identify different signals. Ten different objects were presented for a period of 64 s each. As a minimal requirement it was established that 50% of the respective experimental group be capable of recognizing the objects within half of this time. Whereas 73.3% of the subjects with normal color vision could meet this requirement, none of the subjects in the different groups with color-vision deficiencies could do so. Only 16.1% of the deuteranopic subjects, 33.1% of the deuteranomalous individuals, 16.2% of the protanopic subjects, and 37.6% of the protanomalous individuals detected all objects within 32 s. No appreciable difference in the ability to recognize signals occurred among the different groups of subjects with color-vision deficiencies. PMID- 7795507 TI - Mortality among HIV-infected intravenous drug addicts in Stockholm in relation to methadone treatment. AB - The aim of the study was to estimate the mortality rate and evaluate the causes of death in all diagnosed HIV-positive IDUs in the Stockholm area, 1986-90, and to compare the risk of death of those who received methadone treatment with that of those never admitted to or discharged from the programme. Data were collected from the Swedish National Bacteriological Laboratory, the Methadone Maintenance Programme (MMTP) and the Department of Forensic Medicine, as well as from hospitals in the Stockholm region. In Sweden 90% of all IDUs are HIV-tested. Most deceased IDUs are examined forensically. This examination always includes HIV testing. During the observation period, 472 HIV-infected IDUs were reported from the Stockholm area. Of these addicts 135 participated in the methadone maintenance programme for a shorter or longer time during the study period. Most of them had received the HIV-diagnosis more than 1 year before first entering the programme. Sixty-nine subjects died during the observation period. A majority, 52 persons, died from violence or poisoning. Seventeen died from somatic complications of drug abuse. Nine of them were diagnosed as suffering from AIDS. Eight of the deceased had participated in the MMTP. The relative risk of death from external violence and poisoning was 0.25 (95% confidence interval 0.1-1.0) when participants in the MMTP were compared with HIV-infected IDUs never attending the programme. When all causes of death are compared the relative risk was 0.8. Those patients discharged from the programme have a higher mortality rate than those who never participated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795510 TI - Bilateral herpes simplex virus type 2 keratitis: a clinicopathologic report with immunohistochemical and ultrastructural observations. AB - This report describes the clinical, histopathologic, ultrastructural, and immunohistochemical findings in two corneal buttons from a 13-year-old girl who developed bilateral progressive corneal stromal opacification during childhood. As determined by light microscopy, both corneal buttons were edematous with a chronic inflammatory infiltrate confined to the deep layers of the stroma. We detected intranuclear eosinophilic inclusions in some epithelial cells. We detected herpesvirus particles in stromal keratocytes and endothelial cells by transmission electron microscopy. Immunohistochemistry studies identified concurrent expression of specific herpes simplex virus type 2 antigen in corneal epithelial cells, in keratocytes in the deep layers of the stroma, and in endothelial cells. The cause of progressive bilateral stromal corneal opacification in this child was herpes simplex virus type 2 keratitis. This condition should be considered in the differential diagnosis of progressive, bilateral corneal opacification in children. PMID- 7795509 TI - Involvement of anterior chamber angle structures in disseminated histoplasmosis: report of three cases. AB - This study describes the involvement of anterior chamber (AC) angle structures in patients with disseminated histoplasmosis. The postmortem eyes from three patients (aged 33, 41, and 42 years, respectively) with disseminated histoplasmosis, two of whom had acquired immunodeficiency syndrome, were examined by light microscopy using hematoxylin-eosin, periodic acid-Schiff (PAS), and Gomori's methenamide silver (GMS) stains. Electron microscopy studies of the choroid were performed in one eye. Significant numbers of budding yeast forms of Histoplasma capsulatum measuring 2-5 microns in diameter were observed within the trabecular meshwork, Schlemm's canal and in the deep intrascleral plexuses. All eyes showed massive involvement of the choroidal vasculature, including the choriocapillaris. The organisms were observed freely as well as in small clusters within the cytoplasm of circulating monocytes. The vessels of the limbal conjunctiva (two eyes) and ciliary body (three eyes) contained many Histoplasma organisms. In one eye, several budding yeast were noted in an iris vessel and in occasional histiocytes within the ciliary muscle. Blood smears containing Histoplasma organisms were observed in two cases. None of the patients had an ophthalmologic examination prior to death. Involvement of the intravascular structures of the eye as well as the AC angle was observed in three patients with disseminated histoplasmosis. The fungus most likely reached the AC angle structures by direct hematogenous dissemination or via the aqueous humor by migration from vessels in the ciliary body and iris. An abnormal retrograde blood flow into the AC angle structures may have also played an important role. We suggested that the intraocular pressure be monitored in cases of suspected disseminated histoplasmosis to detect functional alterations indicative of a blockage in the outflow channels. PMID- 7795511 TI - HLA-DR antigen expression in pterygium epithelial cells and lymphocyte subpopulations: an immunohistochemistry study. AB - The purpose of our study was to investigate the role of immune mechanisms in the pathogenesis of pterygium using an immunohistochemical technique. Our material consisted of 35 surgically excised pterygia and 7 samples of normal conjunctiva obtained from an equal number of patients. HLA-DR antigen expression in epithelial cells, B-cells, suppressor and helper lymphocytes, Langerhans' cells, and monocytes/macrophages were studied immunohistochemically in frozen sections using anti-human HLA-DR, anti-CD22, anti-CD8, anti-CD4, anti-CD1a, and anti-LeuM5 monoclonal antibodies. Aberrant HLA-DR antigen expression in epithelial cells was detected in 30 of 35 cases of pterygium. Epithelial cells in samples of normal conjunctiva were found to be negative in HLA-DR antigen expression. HLA-DR antigen expression in pterygium was found to be closely related to the density of T4 cells and, especially, of CD4 lymphocytes. The present findings suggest that an immunopathologic mechanism plays a role in the pathogenesis of pterygium. PMID- 7795512 TI - Tissue plasminogen activator for the treatment of postoperative intraocular fibrinous membranes following cataract surgery. AB - We report on our first two patients treated by intracameral application of tissue plasminogen activator (tPA) for dissolving fibrinous exsudates. Both patients had developed fibrin membranes in the pupillary plane and in the anterior chamber several days after cataract surgery. Injection of 25 micrograms tPA into the anterior chamber resulted in complete dissolution of the fibrin within 1 h of its application. PMID- 7795513 TI - Transscleral suture fixation of posterior-chamber lenses after cataract extraction associated with vitreous loss. AB - From 1987 to 1993, 21 patients who had undergone complicated cataract extraction that was associated with vitreous loss and transscleral suture fixation of the posterior-chamber lens (PC-IOL) in one eye (group A) and uncomplicated in-the-bag implantation of the PC-IOL in the fellow eye (group B) were followed prospectively. The follow-up period was 29.5 months (SD, +/- 17.0 months) in group A and 36.6 months (+/- 24.0 months) in group B. Visual acuity did not differ significantly between the two groups (P = 0.60, Wilcoxon test). In all, 17/21 patients in group A and 16/21 patients in group B achieved a visual acuity of > or = 20/40. Postoperative refractions measured in group A were +0.68 D more hyperopic than those measured in group B (P < 0.04). This result was consistent with the postoperative finding of a significantly deeper anterior chamber in group A (mean, 0.44 mm; P < 0.03). The accuracy of the desired postoperative refraction was poorer in group A. The risk for retinal detachment, cystoid macular edema, and intraocular pressure elevation was increased in patients who had had capsular defects and vitreous loss during cataract extraction. Nevertheless, transscleral suture fixation of PC-IOLs in patients with complicated cataract extractions associated with vitreous loss can give acceptable visual results. We recommend that +0.5 D be added to the calculated IOL power when severe complications require transscleral suture fixation of the PC-IOL during cataract extraction. PMID- 7795514 TI - Endothelial cell morphology after phototherapeutic keratectomy. AB - The purpose of the present study was to investigate endothelial vital reactions after the performance of large central excimer laser keratectomies at various depths. Central 5 mm keratectomies were performed in porcine eyes. The ablations were carried out at depths of 0 (controls), 200, and 400 micron or until perforation occurred. One-third of the corneas were immediately stained with trypan blue and alizarin red, and two-thirds of the eyes were perfused for 1 or 6 h prior to vital staining. The numbers of endothelial cells and damaged cells were assessed. No significant difference was found between 200- and 400 microns deep keratectomies as compared with control corneas at any given time. Perforated corneas showed endothelial and stromal cell damage surrounding the perforation. We conclude that deep excimer laser keratectomies do not affect endothelial cell density and viability for up to 6 h postoperatively. Therefore, excimer laser lamellar keratoplasties appear to be a safe procedure for the underlying endothelium. PMID- 7795516 TI - Perilimbal aneurysms of conjunctival vessels in glaucoma patients. AB - Aneurysms of the conjunctival vessels occur frequently. Such aneurysms have even been described in glaucomatous patients but their significance in this condition is not clear. Because they may be of clinical value in some conditions, the extent of perilimbal aneurysms of the conjunctiva was evaluated in 20 normal tension-glaucoma patients, 20 primary open-angle-glaucoma patients, and 60 controls. The extent of these aneurysms was graded as follows: none (0), faint (1 2), moderate (3-5), and copious (> or = 6). The group frequencies of these categories were 5%, 25%, 10%, and 60% in normal-tension-glaucoma patients; 40%, 40%, 20%, and in primary open-angle-glaucoma patients; and 43%, 32%, 12%, and 13% in control patients, respectively. The incidence of copious perilimbal aneurysms of the conjunctiva was significantly higher in normal-tension-glaucoma patients than in primary open-angle-glaucoma patients and controls (P < 0.0001). Because local medication cannot account for the differences in relation to the control group and because glaucoma patients differed mainly in that normal-tension glaucoma patients had vascular risk factors, the reason for our finding might be related to circulation problems. PMID- 7795515 TI - Comparative effects of atracurium and vecuronium on intraocular pressure. AB - The non-depolarising muscle relaxants atracurium and vecuronium have been found to exert variable effects on intraocular pressure (IOP). The aim of the present study was to assess the influence of atracurium and vecuronium on IOP under standardized clinical conditions. A total of 40 patients undergoing ophthalmic surgery were randomly allocated to 2 study groups. Following oral premedication with dipotassium clorazepate (0.3 mg/kg), anaesthesia was induced with thiopentone (3-4 mg/kg) and alfentanil (15 micrograms/kg). Muscle relaxation was provided according to randomisation, with patients in group 1 receiving 0.3 mg/kg atracurium and patients in group 2 0.07 mg/kg vecuronium. Anaesthesia was maintained with isoflurane (0.5-0.8 vol%) and 70% nitrous oxide in oxygen. The trachea was intubated 4 min after induction and muscle relaxation. A total of nine measurements of IOP were taken in each patient, starting before premedication and ending 5 min after endotracheal intubation. In both groups, there was a significant decrease in IOP after induction of anaesthesia with thiopentone, alfentanil, and atracurium or vecuronium. No difference in IOP was found between the groups. We conclude that both muscle relaxants can be given when increases in IOP have to be avoided. PMID- 7795517 TI - Comparison of temporal and spatiotemporal contrast-sensitivity tests in normal subjects and glaucoma patients. AB - Contrast sensitivity (CS) is reduced in glaucoma diseases. This study compares the value of different CS measurements in glaucoma diagnosis. The study population consisted of age-matched groups of 31 normal subjects (age, 36-59 years; median, 47 years; mean +/- SD, 47.4 +/- 7 years) and 59 glaucoma patients with optic disk damage and visual field defects (age, 36-63 years; median, 53 years; mean +/- SD, 52.3 +/- 7 years). Three types of CS determination were carried out in all subjects: (1) temporal CS of a sinusoidally flickering light (37 Hz) in a ganzfeld bowl, (2) spatiotemporal CS (alternating pattern: 2.5 Hz, 1 cycle/degree; screen size, 5.3 degrees x 4.3 degrees) in a temporal upper retinal area (13.8 degrees horizontal, 4.2 degrees vertical), and (3) spatial CS of a static pattern (three spatial frequencies: 0.6, 3.0, and 12 cycles/degree; screen size, 5.3 degrees x 4.3 degrees) with central fixation. In glaucoma patients the results of CS tests with flickering stimuli were highly significantly correlated with the perimetric mean sensitivity (MS; Octopus G1 program: temporal CS, r = 0.67, P < 0.001; spatiotemporal CS, r = 0.8, P < 0.001). For spatial CS the frequency of 3.0 cycles/degree showed the strongest correlation with MS (r = 0.64, P < 0.001). Only the peripherally localized, spatiotemporal CS showed a strong correlation with optic disk damage (r = 0.59, P < 0.001). On the other hand, the full-field flicker test achieved the best separation between normal subjects and glaucoma patients (specificity, 90%; sensitivity, 71%). These results indicate that tests for temporal resolution are more sensitive to glaucoma defects than are tests for spatial resolution. PMID- 7795519 TI - Approaches to labeling and identification of active site residues in glycosidases. AB - Glycosidases play a key role in a number of biological processes and, as such, are of considerable clinical and biotechnological importance. Knowledge of the identifies of catalytically important active site residues is essential for understanding the catalytic mechanism, for enzyme classification, and for targeted bioengineering of glycosidases with altered characteristics. Here we review and discuss traditional strategies and novel approaches based on tandem mass spectrometry for the identification of the key active site residues in glycosidases. PMID- 7795520 TI - Binding of phosphorus-containing inhibitors to thermolysin studied by the Poisson Boltzmann method. AB - Zinc endopeptidase thermolysin can be inhibited by a series of phosphorus containing peptide analogues, Cbz-Gly-psi (PO2)-X-Leu-Y-R (ZGp(X)L(y)R), where X = NH, O, or CH2; Y = NH or O; R = Leu, Ala, Gly, Phe, H, or CH3. The affinity correlation as well as an X-ray crystallography study suggest that these inhibitors bind to thermolysin in an identical mode. In this work, we calculate the electrostatic binding free energies for a series of 13 phosphorus-containing inhibitors with modifications at X, Y, and R moieties using finite difference solution to the Poisson-Boltzmann equation. A method has been developed to include the solvation entropy changes due to binding different ligands to a macromolecule. We demonstrate that the electrostatic energy and empirically derived solvation entropy can account for most of the binding energy differences in this series. By analyzing the binding contribution from individual residues, we show that the energy of a hydrogen bond is not confined to the donor and acceptor. In particular, the positive charges on Zn and Arg 203, which are not the acceptors, contribute significantly to the hydrogen bonds between two amides of ZGpLL and the thermolysin. PMID- 7795521 TI - Direct evidence of a heterotrimeric complex of human interleukin-4 with its receptors. AB - The mode of binding of interleukin-4 (IL-4) to its two known receptors, specific receptor IL-4R and a shared receptor gamma c, was investigated using gel filtration and gel electrophoresis. A ternary complex between IL-4 and the soluble domains of the two receptors was shown to exist in solution. The association constant between gamma c and the stable complex of IL-4/sIL-4R is in the millimolar range, making the ternary complex a feasible target for crystallization studies. PMID- 7795523 TI - Isoforms of a cuticular protein from larvae of the meal beetle, Tenebrio molitor, studied by mass spectrometry in combination with Edman degradation and two dimensional polyacrylamide gel electrophoresis. AB - Simultaneous sequencing, using a combination of mass spectrometry and Edman degradation, of three approximately 15-kDa variants of a cuticular protein extracted from the meal beetle Tenebrio molitor larva is demonstrated. The information obtained by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) time-course monitoring of enzymatic digests was found essential to identify the differences among the three variants and for alignment of the peptides in the sequence. To determine whether each individual insect larva contains all three protein variants, proteins extracted from single animals were separated by two-dimensional gel electrophoresis, electroeluted from the gel spots, and analyzed by MALDI MS. Molecular weights of the proteins present in each sample could be obtained, and mass spectrometric mapping of the peptides after digestion with trypsin gave additional information. The protein isoforms were found to be allelic variants. PMID- 7795522 TI - Conservative and nonconservative mutations in proteins: anomalous mutations in a transport receptor analyzed by free energy and quantum chemical calculations. AB - Experimental studies on a bacterial sulfate receptor have indicated anomalous relative binding affinities for the mutations Ser130-->Cys,Ser130-->Gly, and Ser130-->Ala. The loss of affinity for sulfate in the former mutation was previously attributed to a greater steric effect on the part of the Cys side chain relative to the Ser side chain, whereas the relatively small loss of binding affinity for the latter two mutations was attributed to the loss of a single hydrogen bond. In this report we present quantum chemical and statistical thermodynamic studies of these mutations. Qualitative results from these studies indicate that for the Ser130-->Cys mutation the large decrease in binding affinity is in part caused by steric effects, but also significantly by the differential work required to polarize the Cys thiol group relative to the Ser hydroxyl group. The Gly mutant cobinds a water molecule in the same location as the Ser side chain resulting in a relatively small decrease in binding affinity. Results for the Ala mutant are in disagreement with experimental results but are likely to be limited by insufficient sampling of configuration space due to physical constraints applied during the simulation. PMID- 7795518 TI - Structural basis of substrate specificity in the serine proteases. AB - Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biological function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in providing strength and specificity of binding, the extent to which binding subsites are interdependent, and the roles of polypeptide chain flexibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why specificity modification can be either straightforward or complex, depending on the particular system. PMID- 7795524 TI - Conformationally constrained analogs of protein kinase inhibitor (6-22)amide: effect of turn structures in the center of the peptide on inhibition of cAMP dependent protein kinase. AB - The high-affinity interaction between protein kinase inhibitor (PKI)(6 22)amide(Thr6-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly- Arg-Arg-Asn- Ala-Ile22 NH2) and the catalytic subunit of cAMP-dependent protein kinase requires both the N-terminal Thr6 to Ile11 sequence of the inhibitor peptide and its C-terminal pseudosubstrate site comprised of Arg15 to Ile22. Small angle X-ray scattering data indicate that PKI(6-22)amide has a compact, rather than extended, structure in solution (Reed J et al., 1989, Biochem J 264:371-380). CD spectroscopic analysis of the PKI peptide led to the suggestion that a beta-turn structure might be located in the -Ala12-Ser-Gly-Arg15-connecting sequence in the middle of the molecule (Reed J, Kinzel V, Cheng HC, Walsh DA, 1987, Biochemistry 26:7641 7647). To investigate this possibility further, conformationally constrained and flexible analogs of PKI(6-22)amide were synthesized and used to study the structure-function relationships of this central portion of the inhibitor. (Des12 14)PKI(6-22) amide exhibited over a 200-fold loss in inhibitory activity. Replacement of the omitted -Ala12-Ser-Gly14-sequence with aminocaprylic acid yielded an analog that regained more than 90% of the lost binding energy. The D alanine14 PKI analog was as potent as the parent peptide, whereas the beta alanine14 and the sarcosine14 analogs were only 10-fold less active. Several peptides that promoted a beta-turn structure at residues 12-15 showed about 200 fold decreases in inhibitory activity. Two constrained analogs that could not assume a beta-turn conformation were only 30-fold less potent than PKI(6 22)amide. Thus, the structure of the central connecting portion of the PKI peptide, encompassing residues 12-15, greatly influences its ability to effectively bind to and inhibit the catalytic subunit. We conclude, however, that a formal beta-turn at this position is not required and is actually detrimental for a high-affinity interaction of PKI(6-22)amide with the enzyme. These results are interpreted in light of the Fourier-transform infrared spectra of the peptide analogs and the crystal structure of the peptide bound at the active site of the protein kinase (Knighton DR et al., 1991b, Science 253:414-420). PMID- 7795525 TI - Stability of ribonuclease T2 from Aspergillus oryzae. AB - The stability of ribonuclease T2 (RNase T2) from Aspergillus oryzae against guanidine hydrochloride and heat was studied by using CD and fluorescence. RNase T2 unfolded and refolded reversibly concomitant with activity, but the unfolding and refolding rates were very slow (order of hours). The free energy change for unfolding of RNase T2 in water was estimated to be 5.3 kcal.mol-1 at 25 degrees C by linear extrapolation method. From the thermal unfolding experiment in 20 mM sodium phosphate buffer at pH 7.5, the Tm and the enthalpy change of RNase T2 were found to be 55.3 degrees C and 119.1 kcal.mol-1, respectively. From these equilibrium and kinetic studies, it was found that the stability of RNAse T2 in the native state is predominantly due to the slow rate of unfolding. PMID- 7795528 TI - Structures of partridge egg-white lysozyme with and without tri-N acetylchitotriose inhibitor at 1.9 A resolution. AB - The three-dimensional structures of native partridge egg-white lysozyme (PEWL) and PEWL complexed with tri-N-acetylchitotriose inhibitor have been determined crystallographically and refined at 1.9 A resolution. Crystals of native and complexed protein are isomorphous and have space group and cell dimensions that are identical to those of hen egg-white lysozyme (HEWL) under similar crystallization conditions. Full occupancy of the trisaccharide in the inhibitor complex has allowed definitive modeling and refinement of all three sugar residues, located at subsites A, B, and C in the PEWL active site. A comparison has been made with HEWL/inhibitor complexes in which coordinates were either not refined (Blake CCF, et al., 1967, Proc R Soc B 167:378-388) or were refined at partial occupancy (Cheetham JC, Artymiuk PJ, Phillips DC, 1992, J Mol Biol 224:613-628). Although the loop comprising residues 70-75 is located on the surface of the protein and not near the active site, it appears to be affected indirectly by trisaccharide binding such that the loop shifts toward the active site and becomes relatively immobilized. The source of this loop movement appears to be the anchoring of Trp62, located in the active site cleft, as it forms a hydrogen bond with O6 of the N-acetylglucosamine at site C. Good electron density for the trisaccharide in the PEWL complex structure shows that Asp 101 is involved in hydrogen bonding interactions with the terminal sugar residue. PMID- 7795527 TI - Purification and preliminary crystallographic studies of penicillin G acylase from Providencia rettgeri. AB - Two isoforms of the heterodimeric enzyme penicillin G acylase (EC 3.5.1.11) from Providencia rettgeri ATCC 31052 (strain Bro1) were purified to near homogeneity. The isoforms exhibited comparable enzymatic activities but differed slightly in the molecular weight and pI of their respective alpha-subunit. The origin of this difference was traced to the partial conversion of the N-terminal Gln of the alpha-subunit to pyrrolidonecarboxylic acid (pyro-Glu). The boundaries of the mature enzyme within the translated DNA sequence of the wild-type propeptide (GenBank M86533) were determined. The results conclusively identified the length of the signal peptide and the position of the spacer cleaved from the propeptide to form the active heterodimer. The molecular weights of the alpha- and beta subunits, based on these termini, were 23.7 and 62.2 kDa, respectively. Both isoforms were crystallized independently as hexagonal bipyramids up to 0.60 mm in diameter in either space group P6(1)22 or P6(5)22 (a = b = 140.5 A and c = 209.5 A) from ammonium sulfate solutions buffered by 50 mM potassium phosphate at pH 7.5. The presence of glycerol, although not required, facilitated crystal growth. Native and heavy atom derivative data were collected to 3.0 A resolution, and the calculation of isomorphous replacement phases is under way. PMID- 7795526 TI - Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins. AB - The primary structural features that render human monoclonal light chains amyloidogenic are presently unknown. To gain further insight into the physical and biochemical factors that result in the pathologic deposition of these proteins as amyloid fibrils, we have selected for detailed study three closely homologous protein products of the light-chain variable-region single-gene family VkIV. Two of these proteins, REC and SMA, formed amyloid fibrils in vivo. The third protein, LEN, was excreted by the patient at levels of 50 g/day with no indication of amyloid deposits. Sequences of amyloidogenic proteins REC and SMA differed from the sequence of the nonpathogenic protein LEN at 14 and 8 amino acid positions, respectively, and these amino acid differences have been analyzed in terms of the three-dimensional structure of the LEN dimer. To provide a replenishable source of these human proteins, we constructed synthetic genes coding for the REC, SMA, and LEN variable domains and expressed these genes in Escherichia coli. Immunochemical and biophysical comparisons demonstrated that the recombinant VkIV products have tertiary structural features comparable to those of the patient-derived proteins. This well-defined set of three clinically characterized human kIV light chains, together with the capability to produce these kIV proteins recombinantly, provide a system for biophysical and structural comparisons of two different amyloidogenic light-chain proteins and a nonamyloidogenic protein of the same subgroup. This work lays the foundation for future investigations of the structural basis of light-chain amyloidogenicity. PMID- 7795529 TI - Refined solution structure of human profilin I. AB - Profilin is a ubiquitous eukaryotic protein that binds to both cytosolic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. These dual competitive binding capabilities of profilin suggest that profilin serves as a link between the phosphatidyl inositol cycle and actin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refined three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twenty structures were selected to represent the solution conformational ensemble. This ensemble of structures has root-mean-square distance deviations from the mean structure of 0.58 A for the backbone atoms and 0.98 A for all non-hydrogen atoms. Comparison of the solution structure of human profilin to the crystal structure of bovine profilin reveals that, although profilin adopts essentially identical conformations in both states, the solution structure is more compact than the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dynamical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% sequence identity and approximately 45% sequence similarity between these two proteins. PMID- 7795530 TI - A proposed structural model of domain 1 of fasciclin III neural cell adhesion protein based on an inverse folding algorithm. AB - Fasciclin III is an integral membrane protein expressed on a subset of axons in the developing Drosophila nervous system. It consists of an intracellular domain, a transmembrane region, and an extracellular region composed of three domains, each predicted to form an immunoglobulin-like fold. The most N-terminal of these domains is expected to be important in mediating cell-cell recognition events during nervous system development. To learn more about the structure/function relationships in this cellular recognition molecule, a model structure of this domain was built. A sequence-to-structure alignment algorithm was used to align the protein sequence of the fasciclin III first domain to the immunoglobulin McPC603 structure. Based on this alignment, a model of the domain was built using standard homology modeling techniques. Side-chain conformations were automatically modeled using a rotamer search algorithm and the model was minimized to relax atomic overlaps. The resulting model is compact and has chemical characteristics consistent with related globular protein structures. This model is a de novo test of the sequence-to-structure alignment algorithm and is currently being used as the basis for mutagenesis experiments to discern the parts of the fasciclin III protein that are necessary for homophilic molecular recognition in the developing Drosophila nervous system. PMID- 7795531 TI - Stabilization of a strained protein loop conformation through protein engineering. AB - Staphylococcal nuclease is found in two folded conformations that differ in the isomerization of the Lys 116-Pro 117 peptide bond, resulting in two different conformations of the residue 112-117 loop. The cis form is favored over the trans with an occupancy of 90%. Previous mutagenesis studies have shown that when Lys 116 is replaced by glycine, a trans conformation is stabilized relative to the cis conformation by the release of steric strain in the trans form. However, when Lys 116 is replaced with alanine, the resulting variant protein is identical to the wild-type protein in its structure and in the dominance of the cis configuration. The results of these studies suggested that any nuclease variant with a non-glycine residue at position 116 should also favor the cis form because of steric requirements of the beta-carbon at this position. In this report, we present a structural analysis of four nuclease variants with substitutions at position 116. Two variants, K116E and K116M, follow the "beta-carbon" hypothesis by favoring the cis form. Furthermore, the crystal structure of K116E is nearly identical to that of the wild-type protein. Two additional variants, K116D and K116N, provide exceptions to this simple "beta-carbon" rule in that the trans conformation is stabilized relative to the cis configuration by these substitutions. Crystallographic data indicate that this stabilization is effected through the addition of tertiary interactions between the side chain of position 116 with the surrounding protein and water structure. The detailed trans conformation of the K116D variant appears to be similar to the trans conformation observed in the K116G variant, suggesting that these two mutations stabilize the same conformation but through different mechanisms. PMID- 7795532 TI - An automatic method involving cluster analysis of secondary structures for the identification of domains in proteins. AB - With a growing number of structures available in the Brookhaven Protein Data Bank, automatic methods for domain identification are required for the construction of databases. Domains are considered to be clusters of secondary structure elements. Thus, helices and strands are first clustered using intersecondary structural distances between C alpha positions, and dendrograms based on this distance measure are used to identify domains. Individual domains are recognized by a disjoint factor, which enables the automatic identification and classification into disjoint, interacting, and conjoint domains. Application to a database of 83 protein families and 18 unique structures shows that the approach provides an effective delineation of boundaries and identifies those proteins that can be considered as a single domain. A quantitative estimate of the interaction between domains has been proposed. The database of protein domains is a useful tool for understanding protein folding, for recognizing protein folds, and for understanding structure-activity relationships. PMID- 7795533 TI - Transmembrane helices predicted at 95% accuracy. AB - We describe a neural network system that predicts the locations of transmembrane helices in integral membrane proteins. By using evolutionary information as input to the network system, the method significantly improved on a previously published neural network prediction method that had been based on single sequence information. The input data were derived from multiple alignments for each position in a window of 13 adjacent residues: amino acid frequency, conservation weights, number of insertions and deletions, and position of the window with respect to the ends of the protein chain. Additional input was the amino acid composition and length of the whole protein. A rigorous cross-validation test on 69 proteins with experimentally determined locations of transmembrane segments yielded an overall two-state per-residue accuracy of 95%. About 94% of all segments were predicted correctly. When applied to known globular proteins as a negative control, the network system incorrectly predicted fewer than 5% of globular proteins as having transmembrane helices. The method was applied to all 269 open reading frames from the complete yeast VIII chromosome. For 59 of these, at least two transmembrane helices were predicted. Thus, the prediction is that about one-fourth of all proteins from yeast VIII contain one transmembrane helix, and some 20%, more than one. PMID- 7795534 TI - Structural features of the uniporter/symporter/antiporter superfamily. AB - The uniporter/symporter/antiporter superfamily is an evolutionarily related group of solute transporters. For the entire superfamily, we have used a new predictive program to identify the transmembrane domains. These transmembrane domains were then analyzed with regard to their overall hydrophobicity and amphipathicity. In addition, the lengths of the hydrophilic loops connecting the transmembrane domains were calculated. These data, together with structural information in the literature, were collectively used to produce a general model for the three dimensional arrangement of the transmembrane domains. PMID- 7795535 TI - Deletion mutants of tyrosine hydroxylase identify a region critical for heparin binding. AB - Phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase constitute a family of tetrahydropterin-dependent aromatic amino acid hydroxylases. It has been proposed that each hydroxylase is composed of a conserved C-terminal catalytic domain and an unrelated N-terminal regulatory domain. Of the three, only tyrosine hydroxylase is activated by heparin and binds to heparin-Sepharose. A series of N-terminal deletion mutants of tyrosine hydroxylase has been expressed in Escherichia coli to identify the heparin binding site. The mutants lacking the first 32 or 68 amino acids bind to heparin Sepharose. The mutant lacking 76 amino acids binds somewhat to heparin-Sepharose and the proteins lacking 88 or 128 do not bind at all. Therefore, an important segment of the heparin-binding site must be composed of the region from residues 76 to 90. All of the deletion mutants are active, and the Michaelis constants for pterins and tyrosine are similar among all the mutant and wild-type enzymes. PMID- 7795537 TI - Integrated case management: the AID Atlanta Model. AB - This article describes the integrated case management model being developed by AID Atlanta, Inc., a community-based AIDS service organization. The case management system features centralized supervision and coordination with decentralized delivery of case management services that avoid duplication of services. The model establishes a system that links clients to appropriate levels of service. The integrated model seeks to address the client's physical, psychological, emotional, and spiritual needs across a continuum of care delivery. The cornerstone of the system is the development of standards of service, systematic documentation, and outcome evaluation criteria. PMID- 7795536 TI - Development of the spectrophotofluorometer and its commercialization. PMID- 7795538 TI - Case management comes of age. PMID- 7795539 TI - A case management program for chemically dependent clients with multiple needs. AB - As part of a 3-year federal demonstration project, San Francisco health clinics provided case management services to chemically dependent individuals who were low-income and often homeless. Many of those participating in the project had also been diagnosed with HIV infection and/or mental illness. The intent of the demonstration project was to use case management as a mechanism for strengthening the linkages between substance abuse treatment and primary care systems. Case management was adopted as the catalyst for increased communication between medical personnel and other service providers to develop a more comprehensive approach to responding to the myriad of client needs. A specially designed management information system (MIS) was developed to help document client information and case management activities, as well as provide a tickler system to improve client continuity. This report integrates both qualitative and quantitative findings to provide a context for understanding case management activities, client problems and successes, and the systemic problems facing clients and case managers in linking primary care, substance abuse treatment, and mental health services. PMID- 7795540 TI - A tool to assess the cognitively impaired elderly. AB - When elderly persons become cognitively impaired, decision-making and case management can be intensely frustrating for health care providers who must make provisions for both short-term and long-term care. Numerous barriers pose challenges to the case managers in addition to those that occur when health care terminology does not fit easily into the legal vocabulary of the judge who makes the ultimate decision naming a guardian or conservator. Ongoing research by the authors has been involved in identifying criteria to determine incompetency by both formal and informal caregivers of cognitively impaired elderly. A scale, currently consisting of 10 criteria, has been developed and continues to be refined by the authors. PMID- 7795541 TI - Coordinated care partnership: case management with physician practices. AB - This article describes the Coordinated Care Partnership Project, operated by The St. Joseph Healthcare System. Funded as one of several demonstration sites by The John A. Hartford Foundation, this project places social work and nurse care managers in selected primary care physician practices in Albuquerque, NM. Lessons learned from the first year of operation are presented, along with implications for the role of case management in primary care practice. PMID- 7795542 TI - Advancing the state of the art: establishing guidelines for long-term care case management. AB - This article describes the results of a 15-month project, supported by a grant from The Robert Wood Johnson Foundation, to develop case management practice guidelines for long-term care. Connecticut Community Care, Inc. (CCCI), a nationally recognized case management agency, was the primary contractor for the grant. CCCI established and convened the National Advisory Committee on Long-Term Care Case Management, a group of case management experts from academia, provider organizations, and state and federal government. CCCI facilitated the work of the committee and had overall responsibility for financial management, data processing, and staff support. The committee's work culminated in a definition of long-term care case management, a set of principles underlying its practice, and the formulation of guidelines. Results and recommendations from the National Advisory Committee will be disseminated to government officials, policymakers, administrators, academicians, geriatricians, care providers, and long-term care community-based case managers. PMID- 7795543 TI - [In memoriam Professor Sir John Mac Michael, foreign honorary member]. PMID- 7795545 TI - [AIDS Commission]. PMID- 7795544 TI - [Academic eulogy of Professor Albert Bruce Sabin, foreign honorary member]. PMID- 7795546 TI - [Type VII C Ehlers-Danlos disease or human dermatosparaxia: the product of a fruitful union of so-called fundamental sciences with human and veterinary clinical medicine]. AB - Ehlers-Danlos type VII C disease is a heritable disorder of the connective tissues and a disease similar to dermatosparaxia in bovine and other animal species. The determination of the pathomechanism of these diseases, the inactivity of the specific protease excising the aminoterminal extension of the type I collagen precursor, resulted of interactive basic and clinical research. PMID- 7795547 TI - [Atrial natriuretic factor and water-sodium homeostasis: concepts and perspectives]. AB - The discovery of an endocrine activity of the heart in 1981 was fundamental in order to understand the regulation of the effective circulatory volume. Indeed, the hormone which is secreted by the atrial cells (ANF) when these are distended suddenly in the presence of an enhanced preload of the heart, acts very rapidly upon the kidneys and the vasomotor tone. Its action restores without delay the effective circulatory volume following the renal elimination of an appropriate fraction of salt and water and attenuates the pressor effects of the increased intravascular volume. In this regard, the hormone is an emergency mediator. ANF may also be a long-term regulator of salt and water homeostasis by modulating the renal excretion of sodium. Finally, its role in pathological conditions such as congestive heart failure or essential hypertension remains to be elucidated. Nevertheless, interesting therapeutic perspectives may be considered, based on the unusual inactivation of ANF by clearance receptors. PMID- 7795548 TI - [Academic eulogy of Professor Albert De Vuyst, titular member and former president]. PMID- 7795549 TI - [In memoriam Professor Andre Lemaire, foreign honorary member]. PMID- 7795551 TI - [The transplantation of syngeneic Schwann cells in medullary lesions: results, limitations and perspectives]. AB - After a central nervous system (CNS) injury, there is only an "abortive regeneration" of axons, while injured axons regenerate vividly in the peripheral nervous system (PNS). This difference is due, at least in part, to the existence in the periphery of Schwann cells and of growth promoting proteins they synthetize. One strategy to promote regrowth of central axons can be therefore, to modify (i.e. "peripheralize") the microenvironment by transplanting biologically active Schwann cells into the lesion site. In a rat model of traumatic paraplegia by inflation of a subdural microballoon, we performed syngeneic transplants of Schwann cells. These cells are cultured from adult dorsal root ganglia and can be kept in vitro for several months. They are transplanted in the injured spinal cord. The grafted Schwann cells are well integrated in the host tissue without detectable inflammatory reaction. Cystic cavitation and astrogliosis are reduced in grafted animals as compared to injured, non-grafted animals. The transplant is invaded by abundant, mainly unmyelinated axons which are immunoreactive for substance P, VIP or CGRP, i.e. transmitters known to be present in DRG afferents. Supraspinal afferents containing 5HT, TH or CCK accumulate at the rostral margin of the graft. Experimental procedures trying to stimulate the invasion of the graft by descending fibers, i.e. by inducing a chemoattraction are therefore of crucial importance for functional recovery. PMID- 7795550 TI - [Molecular cloning and functional expression of glucagon receptors in the liver, the heart and various other tissues]. AB - The mRNA for a glucagon receptor is present in five glucagon-responsive tissues of rat, including the liver, heart, pancreatic islets, kidneys and adipose tissue. The mature mRNA of this receptor is likely to derive from one gene only in all tissues investigated. The maturation of the pre-mRNA requires the splicing of 11 introns. This proceeds stepwise at the 5' end but a single intronless ORF is finally operative. The receptor is a glycoprotein endowed with 485 amino acids (including the signal peptide). PMID- 7795552 TI - [Role of carotid surgery in the prevention of cerebral infarction]. AB - A significant part of transient or permanent cerebral ischemic attacks (CIA) are due to arterio-arterial emboli issued from carotid plaques. Surgery for carotid disobstruction aims to take out emboligenic plaques by endarterectomy (associated to angioplasty or not). The adversaries of surgical treatment sustain two main assertions: 1. carotid stenoses are not very dangerous, because the definitive thromboses they create are easily compensated by the development of collaterals, so that the risk for stroke is low. 2. this low and late risk of spontaneous carotid thrombosis is not greater than the immediate one following carotid surgery. Those objections have been encountered in randomized North American studies (Nascet & Veterans) that have been published in 1991 and 1993. They show the usefulness of correctly done surgical correction as well as for symptomatic as asymptomatic stenoses. So do we it, presenting the results of our series (2.282 procedures in 1.868 patients). The results of our series show a low combined morbidity-mortality rate (1.7%), and a yearly stroke of 1.4%. PMID- 7795553 TI - Hantavirus pulmonary syndrome in Canada. PMID- 7795554 TI - Preliminary report: comparative evaluation of the effectiveness of gas sterilizers. PMID- 7795555 TI - Concise overview of the clinical pharmacokinetics of dideoxynucleoside antiretroviral agents. AB - In this paper aspects of the clinical pharmacokinetics of the antiretroviral agents zidovudine, didanosine and zalcitabine are reviewed. Special attention is paid to possibly altered pharmacokinetics in special circumstances, such as hepatic and renal dysfunction, pregnancy, stage of disease, etc. The dideoxynucleoside antiretroviral agents have some clinical pharmacokinetic properties in common (rapid absorption and elimination), but substantial differences exist in their degree of absorption, metabolism and penetration into the cerebrospinal fluid. All agents display wide interpatient variability in pharmacokinetic parameters. The relevance of therapeutic drug monitoring of antiretroviral agents is also discussed. PMID- 7795557 TI - Preparation and evaluation of sodium diclofenac controlled-release tablets. II. Dibasic calcium phosphate as a retardant in mixtures for direct compression. AB - The dissolution behaviour of a direct compression compact prepared with sodium diclofenac and dibasic calcium phosphate (DCP) in different weight ratios with or without Biosoluble polymer (acrylic-based resin) was investigated in distilled water and in a medium with changing pH. The results indicate that the amount of sodium diclofenac released from the compact was dependent on the amount of drug and DCP used in the compact, and was also controlled by the amount of Biosoluble polymer added. A chemical reaction forming diclofenac acid might occur on the surface of the sodium diclofenac compact during exposure to the acidic medium, which was confirmed by diffuse-reflectance spectroscopy. The tablet with a 1:2 weight ratio of sodium diclofenac to DCP exhibited a sustained-release behaviour, similar to commercial sustained-release products (Voltaren SR-100 and Grofenac Retard), but a lower release rate was found as compared to the commercial products. The dissolution behaviour of the study tablet and the commercial products was found to be dependent on the dissolution medium and the rotating speeds. Glass beads were added to the dissolution assembly to simulate the influence of food, and the enhanced friction between tablet and glass beads might result in a higher dissolution rate of the tablet and the commercial products. PMID- 7795558 TI - Information about drugs in family magazines. AB - Family magazines can play an important role in the diffusion of medical information and information regarding drugs to a 'lay audience'. We describe what kind of drugs are discussed in the family magazines and which information regarding these drugs is given. Furthermore, we look into the information sources for journalists; special attention is paid to the role of the pharmacist: is (s)he recognized by journalists as one of the experts on drugs? Two approaches were used in order to answer the above described research questions: a content analysis of family magazines and in-depth interviews of journalists. Gynaecological products as well as drugs for the central nervous system receive much attention in family magazines. The kind of information given about drugs is limited. Only part of the publications pays attention to side-effects. Patients asking questions about drugs in response to publications in family magazines know the name of a drug but are rarely informed about other aspects of the therapy, such as side-effects. In the provision of information physicians and medical specialists play an important role as sources of information for journalists. There is, however, until now no role for the pharmacist as a source of information on drugs in family magazines. PMID- 7795556 TI - Corticosteroid receptor antagonists: a current perspective. AB - This review aims to highlight a selection of antagonists for the mineralocorticoid and glucocorticoid receptors. Concepts of these receptor systems are described, as is the mechanism of action of these steroids in the brain and periphery. Examples of commonly available and newly synthesized antimineralocorticoids and antiglucocorticoids are given, together with their pharmacological profiles and, when appropriate, clinical and therapeutic applications. PMID- 7795559 TI - Colorimetric determination of some amino acids containing a sulfur group. AB - A simple and rapid colorimetric method for the determination of some amino acids containing a sulfur group is described. The studied compounds are cysteine, cystine and methionine. The method is based on the formation of ferroin, from the reaction of the studied drugs with a mixture of iron(III) and 1,10-phenanthroline and measurement of the absorbance at 512 nm. The procedure has been successfully applied to the assay of the pharmaceutical preparations of the studied drugs after thin-layer chromatographic separation and the results of the studied compounds compare favourably with the official methods. PMID- 7795560 TI - In memoriam Sydney R. Smith, PhD (December 27, 1923-December 12, 1994). PMID- 7795561 TI - Integrating feminist and psychodynamic principles in the treatment of an eating disorder patient: implications for using countertransference responses. AB - Patients who struggle with a tenacious eating disorder commonly stir strong countertransference feelings in therapists. The author describes a patient who for a number of years had been unresponsive to traditional treatment interventions for anorexia nervosa and bulimic tendencies. By combining principles derived from psychodynamic treatment and contemporary feminist thought, the therapist was gradually able to help the patient engage in the treatment process. Managing a variety of strong countertransference feelings was instrumental to the process. The author underscores the need for patients to take greater personal responsibility, develop self-critical and self-analytical capacities, learn to embrace contradictions in the self, and disavow the tendency to harbor fantasies of utopia, perfection, and "cure." PMID- 7795562 TI - Eating disorders, addictions, and unconscious fantasy. AB - Using concepts from object relations theory, the author extends the theories of eating disorders advanced by Freud and Bruch. Ogden's sensation-based autistic contiguous position, Tustin's related concepts of autistic shapes and objects, and Fairbairn's theory of object relations are related to the addictive nature of eating disorders. A clinical illustration demonstrates how these recent theoretical concepts can help explain the unique qualities of the transference and countertransference that develop when working with eating disorder patients. PMID- 7795563 TI - Medical procedures as a source of trauma. AB - Many medical procedures, while necessary and appropriate, may be experienced by a child or adolescent as a trauma, with the medical personnel considered as perpetrators in collusion with the parents. The medical procedures and the conditions requiring them are seldom the focus of routine history-taking or therapeutic process. Nevertheless, the long-range effects of these events may have serious and adverse effects on future development and psychopathology. The author presents several clinical examples. PMID- 7795564 TI - Trauma and violence: the role of early abuse in the aggressive behavior of two violent psychotic women. AB - The author explores the impact of early-life physical and sexual abuse on later life violent behavior in two psychotic women. He proposes that their defending against the aftermath of early and severe abuse is a dynamic factor in the development and maintenance of violent behavior. He also focuses on the influence of maladaptive defensive operations and the impact of abuse on violence triggering hallucinations and delusions. Finally, he contends that psychotherapy can contribute positively to enhanced control of violent behavior, even in severely violent and psychotic patients. PMID- 7795566 TI - Effects of depression and antidepressants on sexual functioning. AB - With serotonergic antidepressants dominating the treatment of depressive disorders, antidepressant-induced sexual side effects have emerged as a major clinical issue. Surprisingly, the effects of depression on sexuality are less well established and more variable than previously thought. It is likely that antidepressants with strong serotonergic effects--selective serotonin reuptake inhibitors, clomipramine, and monoamine oxidase inhibitors--are associated with higher rates of sexual side effects, compared to other antidepressant classes. Orgasmic and ejaculation difficulties are prominent with these medications, although alterations in libido, arousal, and erectile function are also common. Treatment of these side effects includes both general strategies and specific antidotes, such as cyproheptadine, yohimbine, dopamine agonists, and buspirone. PMID- 7795565 TI - Using the SCID-D to assess dissociative identity disorder in adolescents: three case studies. AB - The authors report on the diagnostic assessment of dissociative identity disorder in three adolescents using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D; Steinberg, 1993b), a semistructured instrument for the diagnosis and assessment of dissociative symptoms and disorders. Although the SCID-D has received good-to-excellent ratings for reliability and validity in the adult population, these three cases are the first reports of the results of its administration to younger patients. Comparison of the three adolescent SCID-D interviews with findings in adults indicates that the profiles of the five dissociative symptoms measured by the SCID-D are virtually identical in adolescents and adults. The authors conclude with suggestions for future research regarding dissociative symptomatology in adolescents and outcome studies. PMID- 7795567 TI - The impact of homelessness on children's level of aspiration. AB - In a sample of 39 school-age homeless children, their length of stay in shelters for the homeless was significantly correlated with an index of their level of aspiration. This correlation remained significant even when the effects of the children's intelligence and their performance on a related cognitive task were partialed out. Stories given in response to two Thematic Apperception Test cards by a small sample of these children illustrate the potentially traumatic consequences of homelessness on children's hopes and aspirations. PMID- 7795568 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 7795569 TI - Integrated treatment of social phobia. AB - The importance of recognizing and properly treating social phobia is emphasized by its surprising prevalence and the accompanying marked disability. The author describes how substantial treatment gains can be provided with both psychopharmacological and psychotherapeutic approaches. For those who are significantly affected, a combination approach may be most useful. Appropriate treatment also requires appreciation of comorbid disorders. The author concludes that overall outcome can be enhanced by giving special attention to the dynamic aspects of the therapeutic relationship, as well as by being aware of possible changes in patients' relationships with others as treatment progresses. PMID- 7795570 TI - Anxiety disorders in women. AB - Existing research indicates that anxiety disorders are three times as common in women as in men. Yet true gender-based research is still in its infancy. The author discusses key areas affecting the occurrence of anxiety disorders in women, including medical conditions, epidemiological and diagnostic perspectives, work and the reproductive cycle, trauma (including abuse), and marriage and the family. She notes that future research is likely to produce rapid change and reevaluation in many of these core issues. She concludes that both genders will benefit because evaluation and treatment can truly be tailored to the specific needs of each individual man or woman. PMID- 7795572 TI - Anxiety and addiction: a clinical perspective on comorbidity. AB - Substance use disorders and the anxiety disorders, the two most prevalent mental disorders in the United States, are often comorbid, undiagnosed, and poorly treated. Confusion and controversy over comorbidity can complicate the treatment of both disorders. The author reviews the connections between addiction and anxiety and offers four practical guidelines for clinicians dealing with this comorbidity. PMID- 7795571 TI - Integrated treatment of panic disorder. AB - Epidemiological studies suggest that about 3.5% of the adult United States population meet criteria for panic disorder, and that an additional 2-5% suffer from agoraphobia with or without panic. Both biological and behavioral models have been proposed to elucidate the nature of this disorder. The authors review research findings regarding these models, as well as pharmacological and cognitive-behavioral treatment approaches. The complexity of factors contributing to the disorder suggests the need for an integrated treatment approach involving considerations of combination drug therapy and psychosocial interventions. PMID- 7795573 TI - Anxiety disorders in primary care. AB - Studies indicate that persons with anxiety disorders seek treatment from general medical facilities as often as they do from mental health care settings. Yet primary care providers often do not recognize and treat these individuals effectively, perhaps because anxiety disorders present differently in the general health setting. In light of this situation, the authors note the need to disseminate efficacious treatment approaches to primary care settings. With this goal in mind, they review the prevalence of anxiety in the community and in primary care patients, the presentation of anxiety disorders in primary care, how to improve recognition of anxiety and depression in primary care, and treatment strategies for primary care providers. PMID- 7795574 TI - Challenges to providing integrated treatment of anxiety disorders. AB - Although anxiety disorders are among the most common psychiatric conditions, a number of factors in the current health care scene pose challenges to providing effective, integrated treatment. The author describes nine specific challenges, including lack of recognition of the disorder by both patients and physicians. Other challenges include lack of gender-based research, comorbidity issues, differing etiological and ideological perspectives, the burgeoning of pharmacological treatments, and the tendency to adopt an "either/or," pharmacological versus psychotherapeutic approach to treatment. The author concludes that the overarching challenge is to disseminate the increasing knowledge of these disorders so that practitioners can provide the most effective, integrated treatment. PMID- 7795575 TI - Transgenic animals as models for human disease. AB - Since its first description in 1981 (1), transgenic technology has greatly influenced the focus and direction pace of biomedical research. Introduction of foreign DNA into the genome of animals by microinjection into fertilized oocytes is now used in almost every field of research spanning from oncology, immunology and neurology to cardiovascular medicine. The ability to integrate genes in the germline and their successful expression in the host provides an opportunity to study the role of a certain gene in the initiation and propagation of disease. Transgenic methodology serves as the link between molecular biology, introducing in vitro a defined genetic modification and whole animal physiology, with the resulting in vivo alteration of body function. This potential has been exploited to study the pathophysiological role of human genes. Transgenic animals have been used to study aspects of tumor development, immune regulation, cardiovascular development and atherosclerosis. These studies have provided new insights into the genetic origin of certain diseases and have improved our understanding of pathological processes on the cellular level. As a future goal, these studies may also serve the development of new diagnostic tools or novel therapeutic strategies such as gene therapy. PMID- 7795576 TI - The mechanism responsible for hypertension in a patient with Guillain-Barre syndrome. AB - We report a case of hypertension associated with Guillain-Barre syndrome. In this case, the circadian variation of blood pressure was interrupted. Examination of neurohumoral factors revealed a hyperactive sympathetic nervous system and an increase in plasma renin activity. Clonidine, which acts centrally to inhibit sympathetic outflow, did not suppress serum norepinephrine or epinephrine. These observations suggest that autonomous hyperactivity of the efferent pathway of the sympathetic nervous system may cause the sustained hypertension throughout the day in this case. PMID- 7795578 TI - Alterations of cardiac alpha- and beta-adrenoceptors and inotropic responsiveness in hypertensive transgenic rats harbouring the mouse renin gene (TGR(mREN2)27). AB - In the present study, we investigated the alpha- and beta-adrenoceptor-mediated effects on myocardial force of contraction (using phenylephrine in the presence of propranolol and isoprenaline) and receptor densities (binding studies using [3H]-prazosin and [125I]-iodocyanopindolol) in hypertensive transgenic rats (TGR(mREN2)27) and age-matched Sprague-Dawley rats (SP) as controls. In TGR(mREN2)27 the positive inotropic effects of isoprenaline and phenylephrine were reduced, while the effect of Ca2+ was unchanged. The EC50-values did not differ in both groups. A down-regulation of the beta-adrenoceptors was observed in the hypertrophied left ventricles of transgenic rats, which is postulated to be involved in the reduced beta-adrenoceptor-mediated positive inotropic effect. The alpha-adrenoceptor density was increased, which could represent a compensatory mechanism for the impaired effectiveness of the beta-adrenergic pathway. However, since the effect of alpha-adrenoceptor agonist is not enhanced but even reduced, an uncoupling of alpha-adrenoceptors from post receptor events could play a role in the observed effects. PMID- 7795577 TI - BNP plasma levels during acute volume expansion and chronic sodium loading in normal men. AB - Since the isolation of porcine brain natriuretic peptide (pBNP) in 1988, many aspects of this new endocrine and paracrine system have been elucidated. However, the precise role of human BNP (hBNP) in the regulation of sodium balance and blood pressure in men is still unclarified. We investigated the impact of acute volume expansion and high sodium intake on ANP and BNP plasma levels of 21 healthy male subjects. Following acute infusion of 2000 ml 0.9% saline into a peripheral vein over 30 minutes in a lying position, ANP levels in plasma increased from 110 +/- 14 pg/ml to 199 +/- 18 pg/ml (p < 0.001), while BNP levels remained constant (26 +/- 3 pg/ml before, 28 +/- 3 pg/ml after volume expansion). In a second experiment we investigated the change of ANP and BNP plasma levels after five days of controlled sodium intake (Here blood tests were taken from the probands in an upright position). ANP levels averaged 42 +/- 5 pg/ml after low and 73 +/- 14 pg/ml after high sodium intake. Before starting the diet, the ANP fasting blood level was 56 +/- 6 pg/ml. During both diets, plasma BNP was not altered significantly, but we found a slight insignificant increase after high sodium intake. At the end of each diet we tested ANP and BNP secretion by a physical exercise in an upright position. After high salt intake, BNP plasma levels rose from 32 +/- 4 pg/ml at rest to 45 +/- 7 pg/ml (p < 0.025) after 15 minutes of exercise, while ANP rose from 73 +/- 14 pg/ml to 120 +/- 20 pg/ml (p < 0.001). These results suggest a different regulation of ANP and BNP in normal subjects. ANP secretion is modulated by volume loading and by low or high salt intake while BNP responses to physical exercise. PMID- 7795579 TI - The role of the adrenal medulla in neural control of blood pressure in rats. AB - The role of the adrenal medulla in the regulation of blood pressure was assessed in rats. In conscious intact (SHAM) and adrenal demedullated (DEMED) animals, baseline blood pressures and heart rates were not different. Moreover, equivalent pressor and depressor response curves to norepinephrine and sodium nitroprusside were obtained. Plasma concentration and 24 hr urinary excretion of norepinephrine were not altered by demedullation. However, epinephrine was undetectable in the urine of the DEMED rats. The effectiveness of the demedullation was further evidenced by a greater than 99% decrease in the epinephrine and norepinephrine content of the adrenal glands of DEMED animals. In pithed SHAM rats, electrical stimulation of preganglionic sympathetic neurons (.5 to 16 hz) elicited marked increases in plasma epinephrine indicating adrenal stimulation, whereas in DEMED rats there were no increases. Furthermore, increments in plasma norepinephrine were significantly reduced in DEMED rats, yet the blood pressure increases were greater than in SHAM rats. Thus, adrenal catecholamine release did not contribute to the blood pressure responses, but in fact, may have had an opposite action due to the vasodilatory actions of epinephrine. The results demonstrate that the adrenal medulla is not essential for reflex compensation to a hypotensive challenge or to the blood pressure increases produced to direct neural stimulation. PMID- 7795581 TI - Effect of enalapril on hemorheology in hypertensive patients with renal disease. AB - An open, prospective study was undertaken to investigate the effects of enalapril on hemorheology in patients with renal disease and complicating hypertension. Cellular and plasma determinants of blood viscosity and renal function were measured in 19 patients at baseline and 2, 60 and 120 days after treatment with enalapril (mean dose 5.4; range 2.5-20 mg/day). Within 2 days of starting enalapril there was a significant decrease in apparent blood viscosity measured at high shear rate (-0.15 mPa.s; p < 0.05) which fell further by day 60. The decrease in blood viscosity was primarily the result of hemodilution, as evidenced by a concurrent fall in plasma albumin concentration and plasma viscosity. A small, but significant decrease, in hemoglobin concentration ( 7.4g/l; p = 0.03), and a trend of improved red blood cell (RBC) and white blood cell (WBC) rheological properties may have also contributed to the decrease in blood viscosity. We conclude that enalapril had a beneficial effect on hemorheology in patients with renal disease. The mechanism of the rheological changes appeared to be multifactorial and would be expected to decrease vascular resistance to blood flow. PMID- 7795580 TI - Autoradiographic localization of dopamine D2-like receptors in the rat adrenal gland. AB - The pharmacological profile and the anatomical localization of dopamine D2-like receptors were studied in sections of the rat adrenal gland using combined radioligand binding and autoradiographic techniques with [3H]-spiroperidol as a ligand. [3H]-Spiroperidol was bound to sections of the rat adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time-, temperature- and concentration-dependent and of high affinity with a dissociation constant (Kd) value of 1.6 +/- 0.04 nM and a maximum density of binding sites (Bmax) of 60 +/- 3.6 fmol/mg tissue. Experiments on the pharmacological specificity of [3H]-spiroperidol binding to sections of the rat adrenal gland suggest the labelling of dopamine D3 and/or D4 receptors. The presence of dopamine D3 and D4 receptors in the rat adrenal gland was confirmed by the demonstration of a specific binding for the D3 radioligand [3H]-7-hydroxy N,N-di-n-propyl-2-aminotetralin (DPAT) and for the D4 radioligand [3H]-clozapine. Light microscope autoradiography showed the highest accumulation of silver grains which correspond to [3H]-spiroperidol binding sites in the rat adrenal medulla. In the adrenal cortex, where density of silver grains is about 40% lower than in the medulla, the radioligand is accumulated primarily in the zona glomerulosa and to a lesser extent in the zona reticularis. These findings suggest that dopamine D2-like receptor sites in the rat adrenal gland cortex are primarily involved in the modulation of catecholamine secretion from the medulla and of aldosterone secretion from the cortex. The possible relevance of the occurrence of dopamine D3 and D4 receptor subtypes in the adrenal gland is discussed. PMID- 7795582 TI - Effect of nicorandil on cardiac dysfunction during reperfusion in normotensive and spontaneously hypertensive rats. AB - The cardioprotective effect of nicorandil, an opener of ATP-sensitive potassium channels, was studied in the isolated perfused hearts of the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. Controls received no drug. In the nicorandil group, the hearts were treated with 0.03 to 0.3 mmol/L nicorandil for 15 min before ischemia. Left ventricular developed pressure (LVDP) and end diastolic pressure (LVEDP) at 30 min of reperfusion were significantly lower and larger, respectively, in SHR than in WKY rats. Nicorandil improved LVDP and decreased LVEDP at 30 min of reperfusion in both SHR and WKY rats dose-dependently. The hypertensive heart in the early stage is already susceptible to reperfusion-cardiac dysfunction. Nicorandil has a beneficial effect on the post-ischemic dysfunction in both SHR and WKY rats. PMID- 7795583 TI - Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. AB - Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder which affects the bones of the skull, hands and feet. Previously, we have mapped PS in a subset of families to chromosome 8cen by linkage analysis and demonstrated a common mutation in the fibroblast growth factor receptor-1 (FGFR1) gene in the linked families. Here we report a second locus for PS on chromosome 10q25, and present evidence that mutations in the fibroblast growth factor receptor-2 (FGFR2) gene on 10q25 cause PS in an additional subset of familial and sporadic cases. Three different point mutations in FGFR2, which alter the same acceptor splice site of exon B, were observed in both sporadic and familial PS. In addition, a T to C transition in exon B predicting a cysteine to arginine substitution was identified in three sporadic PS individuals. Interestingly, this T to C change is identical to a mutation in FGFR2 previously reported in Crouzon syndrome, a phenotypically similar disorder but one lacking the hand and foot anomalies seen in PS. Our results highlight the genetic heterogeneity in PS and suggest that the molecular data will be an important complement to the clinical phenotype in defining craniosynostosis syndromes. PMID- 7795585 TI - Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. AB - An earlier study has shown that FAP patients with mutations in codons 136-302 of the APC gene do not develop congenital hypertrophy of the retinal pigment epithelium (CHRPE), whereas those with mutations in codons 463-1387 regularly do. Here we present data on 36 patients from 20 families with mutations in codons 1445-1578. These patients lack CHRPE. Furthermore, with the exception of three prepubertal children all patients with mutations in codons 1445-1578 developed desmoid tumours. This relationship between certain extracolonic manifestations and site of the APC mutation points to a specific role of the APC protein in different tissues. PMID- 7795584 TI - Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. AB - We have identified a 7.5 kb transcript from the dystrophin locus which encodes a novel 140 kDa protein (Dp140). Based on immunoblotting Dp140 consists of the distal rod domain and C-terminus of 427 kDa dystrophin and is found throughout the CNS. This protein is transcribed from an alternative promoter in the dystrophin locus upstream to exon 45. The unique 5' first exon is conserved between rat and human. The transcript has a 1 kb 5' untranslated region, and the first methionine initiation codon occurs in exon 51, predicting a protein of 140 kDa. Several studies report that Duchenne dystrophy patients with deletions in the exon 45-52 region have an increased incidence of cognitive impairment. Such deletions would affect expression of 427 kDa dystrophin and this shorter 140 kDa isoform but not the recently described small distal transcripts Dp116 or Dp71, suggesting particular importance to CNS function. PMID- 7795586 TI - Mucopolysaccharidosis IVA: screening and identification of mutations of the N acetylgalactosamine-6-sulfate sulfatase gene. AB - Mutations causing mucopolysaccharidosis IVA in 15 Japanese and one Caucasian patient were characterized. To screen these mutations, we used a combination of single strand conformation polymorphism analysis and heteroduplex analysis for PCR products of targeted cDNA or genomic DNA. Various small mutations were identified in 23 of 26 alleles, while the other six alleles had large rearrangements. Cycle sequencing of PCR products revealed 15 different mutations, including 12 missense, one nonsense, one frame shift (2 bp deletion) and one splice site mutation, in accord with the broad range of clinical phenotypes. Two alleles have different mutations in the same nucleotide position of exon 3 (R94C, CGC-->TGC; R94G, CGC-->GGC), diagnosed by sequencing and by allelic-specific oligohybridization (ASO). One allele had two amino acid changes, E450V in exon 12 and V488M in exon 13, thereby indicating a double point mutation. All 16 mutations reported were confirmed by restriction enzyme assay or by allelic specific oligohybridization. Transfection of mutagenized cDNAs into patients' fibroblasts showed that all mutations caused completely deficient or markedly decreased N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity, thereby indicating that these mutations were responsible for the enzyme deficiency. PMID- 7795587 TI - DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. AB - Constitutional point mutations in the zinc finger (ZF) region of the Wilms' tumour suppressor gene 1 (WT1) lead to Denys-Drash syndrome (DDS). Patients with this syndrome display renal failure, Wilms' tumour (WT) and pseudohermaphroditism. DDS WT1 mutations fall into three major categories: (a) missense mutations altering amino acids which directly interact with the DNA target; (b) substitution of amino acids involved in zinc complexing; and (c) nonsense mutations leading to the removal of at least two zinc fingers. We have expressed the WT1 zinc fingers as glutathione-S-transferase fusion proteins, with the lysine-threonine-serine (KTS) alternate splice between ZF3 and ZF4 either present or absent. WT1 fusion constructs with all three classes of DDS mutation were also created. Wild-type and mutant fusion proteins were assayed for their DNA-binding affinity using four previously identified WT1 DNA targets: an EGR1 consensus site; murine insulin-like growth factor 2 promoter 2 (IGF2P2); a (TCC)n motif from the PDGFA-chain promoter; and +P5, a genomic fragment isolated by its affinity for WT1 + KTS. WT1-KTS bound all four targets, but WT1 + KTS only bound +P5. All three classes of DDS mutation investigated, with or without KTS, abolished binding to all four targets. This provides evidence that DDS mutations act either as dominant-negative antimorphs, or elicit their effect through disturbed isoform dosage balance. PMID- 7795588 TI - Tissue-specific expression of a FMR1/beta-galactosidase fusion gene in transgenic mice. AB - Fragile X syndrome is one of the most common genetic causes of mental retardation, yet the mechanisms controlling expression of the fragile X mental retardation gene FMR1 are poorly understood. To identify sequences regulating FMR1 transcription, transgenic mouse lines were established using a fusion gene consisting of an E.coli beta-galactosidase reporter gene (lacZ) linked to a 2.8 kb fragment spanning the 5'-region of FMR1. Five transgenic mouse lines showed lacZ expression in brain, in particular in neurons of the hippocampus and the granular layer of the cerebellum. Expression of the reporter gene was also detected in Leydig cells and spermatogonia in the testis, in many epithelia of adult mice, and in the two other steroidogenic cell types, adrenal cortex cells and ovarian follicle cells. Embryonic tissues which showed strong activity of the reporter gene included the telencephalon, the genital ridge, and the notochord. This expression pattern closely resembles the endogenous one, indicating that the 5' FMR1 gene promoter region used in this study contains most cis-acting elements regulating FMR1 transcription. PMID- 7795589 TI - Molecular basis of p(CCG)n repeat instability at the FRA16A fragile site locus. AB - Rare, folate-sensitive fragile sites are the result of the unstable expansion of trinucleotide p(CCG)n repeats, which are normally polymorphic in copy number. Differences in the number and frequency of alleles of the fragile site FRA16A p(CCG)n repeat were observed between different ethnic populations suggesting that certain alleles might be predisposed to instability. Sequence analysis demonstrated that the longer and more variable alleles were associated with loss of repeat interruption. Perfect repeat configuration therefore appears to be a necessary precondition for the instability associated with fragile site genesis. PMID- 7795590 TI - Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. AB - Ocular albinism type 1 (OA1) is an X-linked recessive disorder characterized by a major impairment of visual acuity, nystagmus, strabismus, photophobia and retinal hypopigmentation. From the analysis of patients carrying deletions and translocations involving the distal short arm of the X chromosome (Xp22.3) we have identified a region of approximately 110 kb in which the OA1 gene must lie. We have extensively searched for genes in this region using a variety of techniques which included exon amplification, cDNA selection and direct hybridization of cosmid inserts to cDNA libraries. Putative exons identified by exon amplification were used to screen a human retina cDNA library and several cDNA clones corresponding to an approximately 7.5 kb transcript were isolated and characterized. Transcripts of this newly identified gene were found to be abundant in retina and melanoma and could also be detected in brain, placenta, lung, kidney and pancreas. Interestingly, sequence analysis revealed that this new gene encodes a 1616 amino acid protein sharing significant similarities with the Apical Protein from Xenopus laevis (APX) which is implicated in amiloride sensitive sodium channel activity. The gene, termed APXL (APX-Like), spans approximately 160 kb, contains 10 exons and covers over 70% of the 110 kb critical region for OA1. A truncated pseudogene sharing very high levels of homology with the rat eIF-5 gene, a eukaryotic translation initiation factor, was found to lie in the middle of intron 1. APXL was found deleted in two patients with contiguous gene syndromes including OA1 and in one patient with isolated OA1. Mapping, expression and patient analysis data led us to consider the APXL gene a strong candidate for the OA1 gene. DNA from 57 unrelated patients with OA1 was, therefore, scanned for mutations in the coding region, using both SSCP analysis and direct sequencing. No functionally significant mutation was identified, suggesting that APXL is not directly involved in OA1. Further studies are needed to clarify the physiologic role of this highly conserved gene. PMID- 7795591 TI - Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. AB - Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. We have performed a mutation survey of the RB1 gene in 232 patients with hereditary or non hereditary retinoblastoma. We systematically explored all 27 exons and flanking sequences as well as the promotor. All types of point mutations are represented and are found unequally distributed along the RB1 gene sequence. In the population we studied, exons 3, 8, 18 and 19 are preferentially altered. The range of frequency of detection of germline mutations is about 20%, indicating that other mechanisms of inactivation of RB1 should be involved. The spectrum of mutations presented here should help to improve the clinical management of retinoblastoma and to understand the molecular mechanisms leading to tumorigenesis. PMID- 7795592 TI - Expression of the myotonin protein kinase gene in preimplantation human embryos. AB - We have examined the expression of the myotonin protein kinase gene (MPK) in individual human preimplantation embryos. An allele-specific, reverse transcriptase polymerase chain reaction assay was developed to the required sensitivity using human buccal cells. Human cleavage stage embryos, derived by in vitro fertilisation, were assayed for MPK transcription directly, or after biopsy of a single blastomere used to determine the genotype of the embryo. The maternal and paternal genotypes were determined from cumulus cells and sperm, respectively. MPK gene transcripts were detected in embryos at the 1-cell--4-cell stage of development. Detection of transcripts from the paternally-inherited allele confirmed onset of embryonic MPK gene expression at this very early preimplantation stage. PMID- 7795593 TI - Single cell analysis demonstrating somatic mosaicism involving 11p in a patient with paternal isodisomy and Beckwith-Wiedemann syndrome. AB - Partial isodisomy of 11p has been observed in some patients with Beckwith Wiedemann syndrome. In this study, we demonstrate somatic mosaicism directly through PCR and single cell analysis on blood lymphocytes from a patient with Beckwith-Wiedemann syndrome. Whole genome amplification was performed on single cells and the resultant product was subjected to locus specific microsatellite marker analysis using PCR. Two populations of cells were detected, a population of cells with normal biparental inheritance for chromosome 11 and a population of cells with partial paternal isodisomy of 11p between markers D11S922 (11p15.5) and D11S904 (11p14-p13). These results are consistent with somatic recombination resulting in mosaicism for paternal isodisomy. The use of single cell PCR is ideal for studying the distribution of mosaicism within and between tissues and has been used in this study to identify a cell line with uniparental disomy in a patient with Beckwith-Wiedemann syndrome. PMID- 7795594 TI - Analysis of the CTG repeat in skeletal muscle of young and adult myotonic dystrophy patients: when does the expansion occur? AB - The purpose of this investigation was to analyze the CTG expansion in muscle as compared to lymphocytes DNA in a sample of selected myotonic dystrophy (DM) patients of different ages and degrees of clinical severity, ranging from severe congenital to minimally affected. Results from the present study showed that the size of the CTG repeat was markedly larger in skeletal muscle than in lymphocytes in all DM patients. In contrast to lymphocytes, no significant correlation was found between the size of the CTG expansion in muscle and age at onset. In addition, large expansions were observed in muscle from all adult symptomatic patients independently of the presence of muscle weakness, which raises the question of the value of analyzing CTG expansions in muscle for predicting the severity of the phenotype. Differences between the size of the CTG expansions in muscle as compared to lymphocytes were smaller in affected children suggesting an apparent tendency to increase with aging and reaching a plateau in adulthood. PMID- 7795595 TI - Cloning of a putative human voltage-gated chloride channel (CIC-2) cDNA widely expressed in human tissues. AB - We have cloned a cDNA from the human epithelial cell line T84 whose predicted amino acid sequence shows 93.9% identity with rat CIC-2. Mapping by somatic cell hybrids and polymerase chain reaction localizes the gene corresponding to this cDNA to chromosome 3q26-qter. The major transcription start site assessed by RNA primer extension is 100 nt upstream of the putative translation initiation codon. Analysis of the 5' flanking sequence revealed a high GC content and lack of common transcriptional elements such as TATA and CCAAT boxes. Northern blot analysis indicated wide organ distribution including tissues affected in cystic fibrosis (CF) and expression in an airway epithelial cell line derived from a CF patient. The high degree of sequence similarity and similar tissue distribution to rat CIC-2 suggests that this cDNA encodes the human CIC-2 voltage-gated chloride channel. Since this chloride channel is present in epithelial tissues it may be amenable to manipulation to circumvent the chloride secretion defect observed in CF. PMID- 7795596 TI - Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. AB - Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families. PMID- 7795597 TI - Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes. AB - Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795599 TI - Deletion of the C-terminal end of aspartylglucosaminidase resulting in a lysosomal accumulation disease: evidence for a unique genomic rearrangement. AB - Aspartylglucosaminuria (AGU) is an inborn error of glycoprotein catabolism and represents the only known human deficiency of an amidase, aspartylglucosaminidase (AGA, EC 3.5.1.26). We report here a detailed characterization of a unique 2 kb deletion of the AGA gene in a North American AGU patient. To facilitate the characterization of the deletion, genomic lamda clones spanning the 3' flanking region of human AGA were isolated and sequenced. The breakpoint of the deletion was determined from the patient's DNA by sequencing the genomic region containing the novel junction. The rearrangement involved a nonhomologous recombination with only 2 bp of homology at the deletion breakpoint. The deletion's 5' breakpoint was located in the last intron of AGA, thus abolishing the normal C-terminal exon. This is in contrast to our previous findings indicating that the deletion in the AGA gene would contain only the complete 3' untranslated region and leave the coding region intact (1). The unique feature of this deletion is a triplication of 19 thymidine nucleotides of an inverted Alu repeat, which is located at the deletion 3' breakpoint. The analysis of the patient's AGA cDNA revealed an open reading frame containing a novel C-terminal exon, coding for a 64 amino acid sequence, which has no homology to the normal exon 9 of AGA. This new exon has a functional splice acceptor site at its 5' end, a stop codon, and a polyadenylation signal at the 3' end. Expression of the mutant AGA cDNA in COS cells showed that mutant mRNA is synthesized in equal amounts compared with normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795598 TI - The oculopharyngeal muscular dystrophy locus maps to the region of the cardiac alpha and beta myosin heavy chain genes on chromosome 14q11.2-q13. AB - Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy which presents typically after the age of 50 with progressive eyelid drooping and an increasing difficulty in swallowing. Though OPMD has a world-wide incidence, it is more common in the French Canadian population. We have identified a homogeneous group of families and studied 166 polymorphic markers as part of a genome search before establishing linkage to chromosome 14. We determined that the OPMD locus maps to a less than 5 cM region of chromosome 14q11.2-q13. The maximum two-point lod score in three French Canadian families of 14.73 (theta = 0.03) was obtained for an intronic cardiac beta myosin heavy chain gene (MYH7) marker. The regional localization for the OPMD locus raises the intriguing possibility that either the cardiac alpha or beta myosin heavy chain genes may play a role in this disease. PMID- 7795600 TI - Blepharophimosis syndrome is linked to chromosome 3q. AB - Blepharophimosis syndrome (BPES, blepharophimosis eyelid syndrome) is a distinctive congenital eyelid malformation which can occur sporadically or be inherited in an autosomal dominant fashion. Previous reports have described associated cytogenetic abnormalities on chromosome 3q. We have ascertained and sampled two BPES families with apparent autosomal dominant inheritance and have tested for linkage with 17 polymorphic markers on 3q. Multipoint analysis generated a maximum LOD score of 3.23 using the markers RHO, ACPP and D3S1238. No evidence of genetic heterogeneity was observed. These studies provide the first non-cytogenetic evidence that a defective gene responsible for BPES is located on 3q22. PMID- 7795603 TI - Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus. AB - Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic heterogeneity. In 1991, a recessive form (LGMD2A) was linked to chromosome 15q in a genetic isolate from the Isle of La Reunion. Confirmation of this localization was subsequently reported in Brazilian and northern Indiana Amish pedigrees. Here we report the exclusion of the LGMD2A locus in six Amish kindreds from southern Indiana that are related by multiple consanguineous links to the same northern Indiana families in which the involvement of the chromosome 15 locus was previously demonstrated. These findings indicate unexpected genetic heterogeneity of LGMD in an Indiana Amish isolate. Furthermore, genetic analyses also ruled out the possible involvement of the chromosome 2 locus recently described (LGMD2B), thus demonstrating that a mutation within at least one additional locus leads to this condition. Several candidate genes putatively involved in neuromuscular disorders were also excluded. PMID- 7795601 TI - Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome. AB - For the purpose of initial screening of the human genome in linkage mapping, two overlapping sets of high quality short tandem repeat polymorphisms (STRPs) which span the autosomes have been assembled. The higher density set contains a total of 363 markers with an average heterozygosity of 79% and an average sex-equal genetic distance between markers of 10.5 cM. The lower density set, which is a subset of the other, contains 156 markers with an average heterozygosity of 80% and an average spacing of 26.5 cM. Tri- and tetranucleotide STRPs comprised 47 and 63%, respectively, of the markers within the higher and lower density sets. Markers within the screening sets were selected to have maximum quality, where quality was defined as a blend of high informativeness, strong amplification under standard PCR conditions, low amplification background, and ease in scoring. The screening sets along with combinations of STRPs which can be amplified and electrophoresed simultaneously are available electronically through anonymous ftp. PMID- 7795602 TI - A gene responsible for cavernous malformations of the brain maps to chromosome 7q. AB - Cavernous malformations of the brain are vascular lesions which are present in up to 0.4% of all individuals and which are often accompanied by seizures, migraine, hemorrhage and other neurologic problems. Using linkage analysis and a set of short tandem repeat polymorphisms, a gene responsible for cavernous malformations in a large Hispanic kindred was mapped to the q11-q22 region of chromosome 7. A maximum pairwise lod score of 4.2 was obtained at zero recombination with marker PY5-18 at locus D7S804. Lod scores in excess of 3.0 were obtained with four additional markers closely linked to PY5-18. A broad chromosome 7q haplotype of 33 cM length on the sex average map was shared by all affected individuals indicating that the gene lies between loci D7S502 and D7S479. PMID- 7795604 TI - Evidence from antibody studies that the CAG repeat in the Huntington disease gene is expressed in the protein. AB - The neurodegenerative disorder Huntington disease (HD) appears to be caused by an increase in the number of repeats of the trinucleotide CAG located near the 5' end of the gene. The nucleotide sequences of the cDNA and the gene predict that the HD protein has a molecular weight of 347,000 (3144 amino acids) and that the CAG repeats encode a segment of polyglutamine beginning 17 amino acids from the amino terminus. Because the CAG repeat plays such a critical role in the etiology of the disease, we sought to obtain evidence that the polyglutamine segment is indeed present in the protein. We used two peptides, hd1-peptide (FESLKSFQQ), predicted to lie at amino acid positions 11-19, just amino-terminal to the polyglutamine segment, and hd2-peptide (QQPRNKPLK), predicted to lie at amino acid positions 2531-2539, to induce polyclonal antibodies in NZW rabbits. Both antibodies recognize a protein on Western blots of about 350 kDa in cell lysates from human brain tissue and human and monkey cell lines, including cells from individuals heterozygous and homozygous for the disease. These results suggest that the HD protein in these cells contains the predicted amino terminal segment, and by inference, the segment of polyglutamine, and that the protein is expressed even when only mutant copies of the gene are present. Interestingly, the antibody to hd1-peptide does not recognize the HD protein on Western blots containing lysates from rodent cell lines, whereas the antibody to hd2-peptide does. This discrimination provides a useful means to assay for the presence of the human HD protein in a rodent cell background. PMID- 7795606 TI - Mapping the locus of atrophia areata, a helicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15. AB - Atrophia areata (AA) is an early onset autosomal dominant helicoid peripapillary chorioretinal degeneration, which was first demonstrated to be hereditary in an Icelandic family. It is characterized by bilateral wing-shaped atrophic areas of the retina, radiating from the optic disk. Primary complaints of affected individuals are due to refractive errors and scotomata associated with myopia which increases with age. A genome linkage search with 112 microsatellite DNA markers resulted in the highest probability of location for AA on chromosome 11. We genotyped 18 polymorphic markers on chromosome 11 and seven showed significant linkage to AA. The markers D11S1323 and D11S902 on 11p15 flank the region encompassing the gene for AA. PMID- 7795607 TI - Linkage of posterior polymorphous corneal dystrophy to 20q11. AB - Posterior polymorphous dystrophy (PPMD) is an autosomal dominant disorder of the cornea that is clinically recognized by the presence of vesicles on the endothelial surface of the cornea. The corneal endothelium is normally a single layer of cells that lose their mitotic potential after development is complete. In PPMD, the endothelium is often multi-layered and has several other characteristics of an epithelium including the presence of desmosomes, tonofilaments, and microvilli. These abnormal cells retain their ability to divide and extend onto the trabecular meshwork to cause glaucoma in up to 40% of cases. A large family with 21 members affected with PPMD was genotyped with short tandem repeat polymorphisms distributed across the autosomal genome. Linkage was established with markers on the long arm of chromosome 20. The highest observed LOD score was 5.54 (theta = 0) with marker D20S45. Analysis of recombination events in four affected individuals revealed that the disease gene lies within a 30cM interval between markers D20S98 and D20S108. PMID- 7795608 TI - Missense mutations in the NDP gene in patients with a less severe course of Norrie disease. PMID- 7795605 TI - Expression of the neurofibromatosis 2 (NF2) gene isoforms during rat embryonic development. AB - The neurofibromatosis 2 (NF2) gene product, merlin, encodes a 595 amino acid protein with sequence similarity to a family of proteins linking cell membrane proteins to the cytoskeleton. Two isoforms of merlin have been described which differ by the presence (type 2 merlin) or absence (type 1 merlin) of exon 16 sequences inserted into the extreme carboxyl terminus of the protein. To determine the role of this important negative growth regulator during normal embryonic development, the expression of these two merlin isoforms was examined at representative stages of rat embryogenesis and in adult tissues. Partial sequence analysis of the rat merlin gene demonstrated striking amino acid identity to the published mouse and human merlin gene sequences. In situ hybridization and RT-PCR analyses demonstrated that rat merlin is widely expressed during embryogenesis and early postnatal life in most tissues but becomes restricted to the brainstem, cerebellum, dorsal root ganglia, spinal cord, adrenal gland and testis in adult animals. The elucidation of the pattern of merlin gene expression in adult and embryonic tissues provides the foundations for future studies aimed at determining the function(s) of this protein during cell differentiation and embryonic development. PMID- 7795610 TI - A G-to-T transversion at the +5 position of intron 1 in the glutaryl CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I. PMID- 7795609 TI - A novel point mutation in the Cu/Zn superoxide dismutase gene in a patient with familial amyotrophic lateral sclerosis. PMID- 7795611 TI - Systemic lupus erythematosus in Sao Paulo/Brazil: a clinical and laboratory overview. PMID- 7795612 TI - New York University/Hospital for Joint Diseases experience with intravenous cyclophosphamide treatment: efficacy in steroid unresponsive lupus nephritis. AB - The medical records of patients receiving cyclophosphamide for lupus nephritis between 1987 and 1993 at the New York University/Hospital for Joint Diseases Lupus Study Group Institutions were retrospectively reviewed. We identified 45 patients (38 female, seven male) who received a mean of 9 +/- 1 (range 2-23) pulses of intravenous cyclophosphamide for diffuse proliferative glomerulonephritis (n = 28), focal proliferative glomerulonephritis (n = 7), membranous nephropathy (n = 5), mesangial nephropathy with sclerosis (n = 1) or nephritis without biopsy (n = 4). Forty-two of the 45 patients received cyclophosphamide after failing steroid therapy. During a follow-up period of 52 +/- 3 months, nine patients progressed to end-stage renal disease (ESRD) with three additional patients experiencing a doubling of the creatinine and two patients persistent nephrotic range proteinuria. There were no deaths directly attributable to cyclophosphamide and no patients developed hemorrhagic cystitis or malignancy. Ten of 37 women had ceased menstruating prior to cyclophosphamide therapy. Treatment-associated amenorrhea occurred in only three patients all over 27 years of age. Intermittent intravenous cyclophosphamide therapy of lupus nephritis is well tolerated and usually effective in maintaining renal function in patients unresponsive to steroids although, in our experience, 20% of patients developed ESRD and a total of 14 of 45 (30%) patients had unsatisfactory outcomes. PMID- 7795614 TI - In utero identification and therapy of congenital heart block. AB - To determine the feasibility and effectiveness of prenatal therapy of congenital heart block (CHB), information was sought regarding the timing of identification of CHB in 72 pregnancies and the outcome of those pregnancies in which the mothers were administered corticosteroids. Mailed questionnaires with telephone follow-up, data from primary physicians and chart review were utilized. In 38 (53%) of affected pregnancies CHB was identified between 16 and 24 weeks of gestation, in 17 (24%) between 25 and 30 weeks of gestation, in 8 (11%) between 31 and 37 weeks, and in 5 (7%) between 38 and 40 weeks. In four pregnancies the timing was unknown. Five women were taking prednisone for disease activity prior to the discovery of CHB and in six other women prednisone therapy was initiated at or about the time CHB was identified. In 19 pregnancies, women were given fluorinated steroids (available to the fetus in an active form) as attempted therapy after the discovery of CHB. Of these, one fetus with second degree block reverted to sinus rhythm and two with third degree block exhibited an improvement in the degree of block. In eight fetuses pleural and/or pericardial effusions resolved. In conclusion, the gestational period of heightened fetal vulnerability for the development of heart block is in the mid second to early third trimester. Although there is no evidence that maternal prednisone should be used prophylactially, fluorinated steroids may be efficacious after the identification of heart block, particularly with regard to an associated myocarditis. PMID- 7795613 TI - Prognostic determinants in lupus nephritis: a long-term clinicopathologic study. AB - Over the past 50 years, survival has improved in patients with systemic lupus erythematosus and associated nephritis. Yet, there are few long-term outcome studies in patients with well-defined nephropathy. We examined the outcome of 439 patients with lupus nephritis who were seen at the Mayo Clinic between 1964 and 1986 in whom renal biopsies were assessed using the World Health Organization (WHO) classification. There were 341 women and 98 men (mean +/- s.d., age 33.5 +/ 14 years); 200 (46%) patients were hypertensive and 249 (57%) had impaired renal function at renal biopsy. All WHO morphologic classes were represented and 339 (77%) patients had class III, IV and V (the more severe forms of nephritis). Follow-up averaged 10.2 years per patient. At last contact, 286 (65%) patients were alive and 153 (35%) were dead. Overall patient survival was 80%, 69% and 53% at 5, 10 and 20 years after biopsy that was significantly worse than expected survival (P < 0.001). Ten-year cumulative patient survival improved comparing earlier to more recent time spans: 64% in 231 patients seen during 1964-75; 76% in 2089 patients studied during 1976-86 (P = 0.03). Survival free of renal failure was 83%, 74% and 64% at 5, 10 and 20 years, and survival was unfavorably influenced by progressive WHO class, hypertension, impaired renal function, nephrotic range proteinuria, hypoalbuminemia and anemia. Multivariate analysis found impaired renal function, increased urine protein, anemia and younger age to be independent predictors of renal failure. WHO class was not a significant predictor when adjusted for these four factors. Cardiovascular events accounted for 48% of the known deaths and were equally distributed across all WHO classes, followed by infections, renal failure, malignancy, respiratory failure and gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795616 TI - False positive seroreactivity to Borrelia burgdorferi in systemic lupus erythematosus: the value of immunoblot analysis. AB - The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot analysis as a tool to differentiate true from false positive ELISA. Sera were obtained from patients with SLE (n = 35), rheumatoid arthritis (n = 26), seronegative arthritis (n = 28) and Lyme disease (n = 18). Reactivity to B. burgdorferi antigens was analysed by two available diagnostic techniques: ELISA and immunoblot. Correlations were made between seroreactivity to B. burgdorferi and standard serological tests of autoimmunity: antibodies to nuclear antigens, dsDNA, cardiolipin, SSA and SSB. Seroreactivity to B. burgdorferi antigens by the ELISA system was detected in 40% of patients with SLE, 8% of patients with rheumatoid arthritis and 4% with seronegative arthritis. Among patients seropositive by ELISA, immunoblots were negative in all cases. However, eight of 14 patients with rheumatoid arthritis (57%) showed cross-reactivity to multiple borreli antigens. No significant correlations were found between Lyme seropositivity by ELISA and other autoantibodies except IgM rheumatoid factor (r = 0.61, P < 0.01) in patients with rheumatoid arthritis. IN CONCLUSION: a positive ELISA for Lyme disease was found in up to 40% of patients with established SLE and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795615 TI - Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome? AB - Anticardiolipin (aCL) and anti-beta 2-glycoprotein I(anti beta 2GPI) antibodies have been shown in animal models as not cross-reacting antibody populations. This observation prompted us to prove if anti-beta 2GPI exist in human sera by using a reliable method and then to investigate if these are independent from aCl antibodies. We have developed a new ELISA for the detection of anti-beta 2GPI antibodies employing the coating of the protein in carbonate buffer to irradiated microtitre plates and the filtration of serum samples, that makes irrelevant the binding to the uncoated wells. IgG F(ab)2 fragments from IgG positive sera were shown bind beta 2GPI, providing that the binding was a specific antibody binding, mediated by the antigen binding site of the antibody molecule: moreover the antibodies were not able to differentiate native and delipidated beta 2GPI coated plates, making a possible role of a phospholipid contaminant unlikely. On the other hand, the phosphorus content of native as well as delipitated beta 2GPI was undetectable. IgG, but not IgM, anti-beta 2GPI antibodies were classically inhibited by the addition of soluble beta 2GPI, while cardiolipin liposomes appear to modify the reaction in a completely different way, possibly by the described interaction between cardiolipin and beta 2GPI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795618 TI - Association of anticardiolipin antibodies and abnormal nailfold capillaroscopy in patients with systemic lupus erythematosus. AB - Anticardiolipin antibodies (aCL) are found in about 40-50% of patients suffering from systemic lupus erythematosus (SLE) and their presence carries an increased risk of thromboembolism. Since there is a high prevalence of nailfold capillary abnormalities in patients with SLE, we studied the relationship between aCL and skin microcirculatory changes or vascular symptoms in 51 consecutive patients with SLE (49 women, 2 men, 34.8 +/- 13.7 years). Twenty-two patients (43.1%) had positive aCL (IgG 22 (5-60) GPL; IgM 5 (3-16.5) MPL; median titre and range) and 12 (54.5%) of them had abnormal capilloscopic findings. By contrast, among the 29 patients without aCL, only six (20.7%) had an abnormal capillaroscopy (P = 0.027). There was no correlation between either aCL or capillaroscopy and Raynaud's phenomenon. These results show a relationship between aCL and nailfold capillary changes in patients with SLE, suggesting a direct damage of the vascular endothelium by aCL. PMID- 7795617 TI - IgA antiphospholipid antibodies in HTLV-1-associated tropical spastic paraparesis. AB - A retrovirus, human T cell lymphotropic virus type 1 (HTLV-1), is an essential but not a sufficient aetiologic factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for treponemal infections (BFP-STS), we used ELISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies occur in about 26% of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-1 or other nontreponemal infections. PMID- 7795619 TI - Anti-neuronal antibodies in antiphospholipid syndrome with central nervous system involvement: the difference from systemic lupus erythematosus. AB - The presence of antineuronal antibodies was compared in 43 patients with primary aPLS and 57 patients with neuropsychiatric SLE. Fifty-eight patients with Guillain-Barre syndrome and 72 normal healthy donors served as control groups. Seventeen patients in the study group had aPLS associated with CNS involvement. Antineuronal antibodies were studied in the sera employing a novel flow cytometric assay. The frequency of antineuronal antibodies in patients with aPLS and CNS involvement was not significantly different from that of patients with aPLS without CNS disease or from that found in the control groups (12%, 19% and 7%, respectively). However, it was significantly different from that found in SLE patients with CNS involvement (60%) (P < 0.001). Our results provide further evidence that unlike CNS-SLE, the major mechanism of CNS involvement in patients with primary aPLS might not be autoantibody (antineuronal) mediated, but rather 'thrombotic' in origin, or due to yet unknown factors. PMID- 7795620 TI - Skeletal muscle lymphocytic vasculitis in systemic lupus erythematosus: relation to disease activity. AB - Lymphocytic vasculitis (LV) characterises systemic lupus erythematosus (SLE) and this potentially reversible lesion, which may be subclinical, may imply overt systemic disease activity. Needle quadriceps muscle biopsy was performed in 26 unselected patients with SLE and the presence of LV in these muscle specimens was compared with SLE disease activity scored using the British Isles Lupus Assessment Group Index (BILAG). Ten of the 22 patients with active disease showed evidence of LV compared with none of the four patients with inactive disease. In the patient group with LV, significantly higher ESR and urine neopterin values were found with P = 0.002 and P = 0.02, respectively compared with patients without LV. Features of vasculitis (as defined by BILAG) were also significantly more common in these patients (P = 0.005). None of the other parameters, including creatine kinase, were significantly different between the two patient subgroups. Thus, LV in needle quadriceps muscle biopsy specimens is a further valuable marker of disease activity in patients with SLE and might provide histological evidence of a systemic vasculitic process in a group of patients with diverse clinical manifestations. PMID- 7795621 TI - Clinical manifestations of hepatic arteritis in systemic lupus erythematosus. AB - Hepatic arteritis is a rare complication in systemic lupus erythematosus (SLE). Information about its clinical manifestations is still very limited. Elevated serum r-glutamyl transpeptidase and alkaline phosphatase levels, but without elevated bilirubin and transaminase levels, were found in the present report to be the clinical presentation of hepatic arteritis. This clinical picture originally suggested a disease of the biliary tree. Hepatic arteritis must be included in the differential diagnosis of biliary tract disorders in SLE. PMID- 7795622 TI - Ischemic optic neuropathy and high-level anticardiolipin antibodies in primary Sjogren's syndrome. AB - A 39-year-old woman with recurrent severe anterior ischemic optic neuropathy in the setting of Sjogren's syndrome was found to have high-titer IgM anticardiolipin antibodies (aCL) that were enhanced by the phospholipid-binding glycoprotein beta 2GP1. The recognition of IgM aCL-associated vasculopathy as a possible etiologic factor in the optic neuropathy in Sjogren's syndrome may be relevant in deciding appropriate therapy. PMID- 7795623 TI - Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion. AB - In this report we describe a patient with systemic lupus erythematosus who was clinically stable after treatment with the antimalarial drug chloroquine and pulse cyclophosphamide therapy. Three months after the discontinuation of chloroquine, the patient developed cilioretinal artery occlusion that was the only the manifestation of a clinical flare-up without evidence of clinical disease activity elsewhere. This case report confirms the clinical belief that the antimalarial agents can maintain the clinical quiescence of systemic lupus erythematosus and its discontinuation is associated with an increase in the risk of clinical flare-up. PMID- 7795625 TI - Prevalence of antinuclear antibodies in a Huichol population of Mexico. PMID- 7795624 TI - Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus. AB - A 34-year-old woman with stable systemic lupus erythematosus (SLE) treated with low-dose prednisone and hydroxychloroquine developed multiple bilateral pulmonary nodules. Open lung biopsy documented lymphocytic interstitial pneumonitis (LIP). LIP should be considered in the differential diagnosis of nodular pulmonary lesions in patients with SLE. PMID- 7795626 TI - Thrombomodulin in human brain microvasculature. PMID- 7795627 TI - The definition for coexistent rheumatoid arthritis and systemic lupus erythematosus. PMID- 7795628 TI - Systemic lupus in children: daughter of the Hydra? PMID- 7795629 TI - Serological markers of disease activity in systemic lupus erythematosus. AB - When measured serially by Farr assay at a frequency of approximately once a month, changes in levels of anti-dsDNA appear to be a good predictor of clinical disease activity. Although the role of antibodies to the RNA component of snRNP awaits further studies, measurement of anti-UsnRNP antibody levels seems to be of limited value in monitoring lupus patients in clinical practice. The same holds for antibodies to SSA (Ro) and anti-histone antibodies. More recently described antibodies to C1q are probably useful in the follow-up of SLE patients suspected of proliferative renal involvement. The best alternative to measuring levels of the antibodies mentioned before is probably serial analysis of activation of the complement cascade. Levels of complement factors like C3, C4 and, functionally, CH50 remain a useful parameter for monitoring disease activity in SLE, although fluctuations in anti-dsDNA as measured by Farr assay seem superior with respect to sensitivity and specificity for an ensuing relapse. Despite the problems in sampling, measuring levels of activated split products of complement factors like C3a, C3d or C5a may prove to be a valuable tool in the follow-up of lupus patients. The involvement of the endothelial surface is illustrated by rising sVCAM-1 levels prior to relapses in SLE. Although one could expect that subsequent inflammation should be reflected by increased levels of inflammatory molecules like CRP and IL-6, the use of these molecules as predictors of lupus activity seems limited. Interferon-alpha as a direct reflector of the effector phase seems, however, rather promising in this respect and awaits longitudinal studies to analyse the possible relation with clinical disease activity and other serological parameters. PMID- 7795630 TI - Mosaic of anti-endothelial antibodies. Review of the first international workshop on anti-endothelial antibodies: clinical and pathological significance Milan, 9 November 1994. PMID- 7795631 TI - Pax genes--paired feet in three camps. PMID- 7795632 TI - BRCA1: more than a hereditary breast cancer gene? PMID- 7795633 TI - Progress in prostate cancer. PMID- 7795634 TI - Triad-DNA: a model for trinucleotide repeats. PMID- 7795635 TI - Towards fully automated genome-wide polymorphism screening. PMID- 7795637 TI - Unique features of the CAG repeats in Machado-Joseph disease. PMID- 7795636 TI - A somatic BRCA1 mutation in an ovarian tumour. PMID- 7795638 TI - Anastasia and Anna Anderson. PMID- 7795639 TI - Positional cloning moves from perditional to traditional. AB - The technique of positional cloning has become a familiar component of modern human genetics research. After a halting start in the mid-1980s, the number of disease genes succumbing to cloning efforts based solely on pinpointing their position in the genome is growing exponentially. More than 40 genes have been identified so far. But the positional candidate approach, which combines knowledge of map position with the increasingly dense human transcript map, greatly expedites the search process and will soon become the predominant method of disease gene discovery. The challenge ahead is to apply such methods to identifying genes involved in complex polygenic disorders. PMID- 7795641 TI - Sequence analysis reveals a beta-thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. AB - beta-Thalassaemia is manifested by severe anaemia and extensive bone pathology. Similar pathology may also result from other forms of anaemia. To clarify the precise cause, we performed DNA analyses on archaeological remains of a child with severe bone pathology. We found homozygosity for frameshift in codon 8 of beta-globin, causing a beta-null phenotype. Paradoxically, the child died when eight years old, whereas such patients are transfusion dependent from early infancy. An infrequent polymorphic marker in the child's DNA, and information from present-day patients, indicated that amelioration of the clinical condition was due to elevated fetal haemoglobin production. Thus this analysis provided not only precise diagnosis of a genetic disease but also allowed clarification of the molecular mechanism underlying the clinical presentation. PMID- 7795640 TI - Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. AB - Paired box (PAX) genes play a critical role in human development and disease. The PAX2 gene is expressed in primitive cells of the kidney, ureter, eye, ear and central nervous system. We have conducted a mutational analysis of PAX2 in a family with optic nerve colobomas, renal hypoplasia, mild proteinuria and vesicoureteral reflux. We report a single nucleotide deletion in exon five, causing a frame-shift of the PAX2 coding region in the octapeptide domain. The phenotype resulting from the PAX2 mutation in this family was very similar to abnormalities that have been reported in Krd mutant mice. These data suggest that PAX2 is required for normal kidney and eye development. PMID- 7795642 TI - Chromosome specific paints from a high resolution flow karyotype of the mouse. AB - Chromosomes from antigen stimulated B-cells from spleens of inbred mice have been separated using flow cytometry into 18 distinguishable peaks. Using locus specific oligonucleotides and fluorescence in situ hybridization to banded metaphase spreads, 15 individual chromosomes were identified: 1, 2, 3, 6, 7, 8, 9, 11, 12, 16, 17, 18, 19, X and Y. The remaining six chromosomes, occurring as pairs in three peaks, 4 with 5, 10 with 13, and 14 with 15, were resolved by flow sorting chromosomes from mice carrying an appropriate homozygous translocation and 4, 5 and 14 have been isolated in this way. This is the first demonstration of how a complete set of mouse chromosome paints can be produced. PMID- 7795643 TI - A site-directed chromosomal translocation induced in embryonic stem cells by Cre loxP recombination. AB - We have developed a strategy for chromosome engineering in embryonic stem (ES) cells that relies on sequential gene targeting and Cre-loxP site-specific recombination. Gene targeting was first used to integrate loxP sites at the desired positions in the genome. Transient expression of Cre recombinase was then used to mediate the chromosomal rearrangement. A genetic selection relying on reconstruction of a selectable marker from sequences co-integrated with the loxP sites allowed detection of cells containing the Cre-mediated rearrangement. A programmed translocation between the c-myc and immunoglobulin heavy chain genes on chromosomes 15 and 12 was created by this method. This strategy will allow the design of a variety of chromosome rearrangements that can be selected and verified in ES cells or activated in ES cell-derived mice. PMID- 7795644 TI - Domain organization of allele-specific replication within the GABRB3 gene cluster requires a biparental 15q11-13 contribution. AB - Imprinting marks the parental origin of chromosomes, resulting in allele-specific changes in chromatin organization, transcription and replication. We report a 50 60 kb domain of allele-specific replication between the gamma-aminobutyric acid receptor subunit beta 3 (GABRB3) and alpha 5 (GABRA5) genes. Replication of this domain occurs in early S phase on the maternal chromosome 15 but is delayed until the end of S phase on the paternal homologue. In contrast, the genomic regions flanking this domain exhibit paternal earlier replication in mid to late S phase. Uniparental disomy or hemizygous deletion of chromosome 15 results in altered allele-specific replication kinetics compared with normals, suggesting that allele-specific replication within the GABRB3/A5 region may be regulated by reciprocal imprints on the maternal and paternal chromosomes. PMID- 7795645 TI - Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. AB - A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex. PMID- 7795646 TI - In vivo amplification of the androgen receptor gene and progression of human prostate cancer. AB - Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11-q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations. PMID- 7795647 TI - A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. AB - Imprinting, the differential expression of the two alleles of a gene based on their parental origin, requires that the alleles be distinguished or marked. A candidate for the differentiating mark is DNA methylation. The maternally expressed H19 gene is hypermethylated on the inactive paternal allele in somatic tissues and sperm, but to serve as the mark that designates the imprint, differential methylation must also be present in the gametes and the pre implantation embryo. We now show that the pattern of differential methylation in the 5' portion of H19 is established in the gametes and a subset is maintained in the pre-implantation embryo. That subset is sufficient to confer monoallelic expression to the gene in blastocysts. We propose that paternal-specific methylation of the far 5' region is the mark that distinguishes the two alleles of H19. PMID- 7795648 TI - X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. AB - X-linked thrombocytopenia (XLT) is a rare recessive hereditary disorder characterized by isolated thrombocytopenia with small-sized platelets. The XLT locus has been located to chromosome Xp11 by linkage analysis, which is also where the recently cloned Wiskott-Aldrich syndrome (WAS) gene, maps. The relationship between XLT and WAS has long been debated; they might be due to different mutations of the same gene or to mutations in different genes. We now show that mutations in the WAS gene, different from those found in WAS patients, are present in three unrelated male patients with isolated thrombocytopenia and small-sized platelets. Our results demonstrate that XLT and WAS are allelic forms of the same disease, but the causes of the differences need to be further investigated. PMID- 7795649 TI - A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q. AB - Maturity-onset diabetes of the young (MODY) is a subtype of non-insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likely within a 7 centimogran interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic beta-cell function. PMID- 7795650 TI - The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice. AB - High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To investigate the in vivo regulation of apo(a), we have created several lines of YAC transgenic mice containing a 110-kb human apo(a) gene surrounded by greater than 60 kb of 5' and 3' flanking DNA. Studies in humans have suggested that acute phase inducers increase and sex steroids decrease apo(a) concentrations, but these results are controversial. Analysis of the YAC transgenic mice conclusively supports the hypothesized role of sex steroids and refutes the suggested role of acute-phase inducers in regulating the apo(a) gene. PMID- 7795651 TI - Optical mapping of lambda bacteriophage clones using restriction endonucleases. AB - Optical mapping is an emerging single molecule approach for the rapid generation of ordered restriction maps, using fluorescence microscopy. We have improved the size resolution of optical mapping by imaging individual DNA molecules elongated and fixed onto derivatized glass surfaces. Averaged fluorescence intensity and apparent length measurements accurately determined the mass of restriction fragments 800 basepairs long. We have used optical mapping to create ordered restriction maps for lambda clones derived from the mouse pygmy locus. PMID- 7795653 TI - Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression. AB - We have characterized expression of the familial breast and ovarian cancer gene, BRCA1, in cases of non-hereditary (sporadic) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells. BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer. Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells, but had no effect on non-mammary epithelial cells. These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression. PMID- 7795652 TI - Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. AB - The BRCA1 gene on chromosome 17q21 is responsible for an autosomal dominant syndrome of increased susceptibility to breast and ovarian cancer but no somatic mutations in tumours have yet been described. To study the potential role of BRCA1 in sporadic carcinogenesis, we analysed the genomic DNA of tumour and normal fractions of 47 ovarian cancers for mutations in BRCA1 using the single strand conformation polymorphism technique. We now describe somatic mutations in the DNA of four tumours which also had loss of heterozygosity (LOH) at a BRCA1 intragenic marker. Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers. PMID- 7795654 TI - Ipsilateral visual projections in non-eutherian species: random variation in the central nervous system? AB - The published descriptions of ipsilateral visual pathways in non-eutherian species are reviewed. Such pathways exist in members of all vertebrate classes; since they exist in agnathans, it is suggested that the presence of ipsilateral visual projections is the ancestral condition. None of the published attempts to explain the considerable interspecific variation of these pathways can be generalised to all vertebrate species: in particular, this variation is not generally related to the degree of overlap of the visual fields, to a particular mode of life, nor to taxonomic position within a given vertebrate category and cannot consistently be explained by variation at the albino locus. It is suggested that this variation is the result of purely random variation of unidentified elements of the genetic material or of epigenetic mechanisms and hence that ipsilateral visual projections are functionally neutral. This conclusion is supported by some extremely fragmentary behavioral data indicating that the information they provide is redundant. PMID- 7795655 TI - Role of glial-derived nexin in neuronal differentiation and in acute brain injury and potential involvement in exacerbation of neurodegeneration in Alzheimer's disease. PMID- 7795656 TI - Cell types in the rostral nucleus of the solitary tract. AB - The rostral subdivision of the nucleus of the solitary tract (rNST) is not laminated or otherwise organized into clearly segregated cell types. Although a variety of experimental approaches have yielded a wealth of information, the definition of cell types in this nucleus has been difficult, as reflected in the sometimes contradictory literature on morphological cell typing. The present review discusses how rNST neurons have been classified in the past and adds to the evidence that distinct neuron types exist in this nucleus. Consistencies in the literature, as well as inconsistencies among studies, are discussed. Furthermore, we have included a summary of our own results that help provide additional data relevant to cell typing. The definition of cell types in other central nervous system nuclei has helped our understanding of the organization of these nuclei and our understanding of the relationships between the morphology and function of neurons. It is hoped that this synthesis of the extant literature will facilitate the many ongoing efforts to correlate neuronal morphology and physiology in the gustatory system. PMID- 7795657 TI - Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats. AB - The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers. PMID- 7795658 TI - The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. AB - Phencyclidine (PCP) and ketamine can induce a model psychosis in drug addicts and exacerbate the symptoms of chronic schizophrenics. The model psychoses these drugs induce mimic a variety of schizophrenic symptoms, including flattened affect, dissociative thought disorder, depersonalization and catatonic states. These symptoms can persist for prolonged periods and chronic PCP and ketamine addicts have persisting memory deficits. Dizocilpine (MK-801) is a simpler drug than PCP or ketamine in its actions, but it shares with both the property of blocking in a non-competitive manner the N-methyl-D-aspartate (NMDA) ion-channel. Behavioral observations and drug-discrimination studies in animals indicate that PCP and dizocilpine are similar in their effects and they both have a neurotoxic effect on neurons in posterior cingulate cortex. Recent studies have indicated that both of these drugs, when given continuously for several days, further induce neuronal degeneration in other limbic structures. These include brain regions of rats related to olfaction, associated limbic structures such as piriform cortex and posterior regions of entorhinal cortex and in it's projections, through the perforant pathway, to dentate gyrus and other cells in ventral hippocampus. These degenerative consequences may be excitatory neurotoxic effects, for these compounds also induce an elevation in glucose metabolism maximal in just those structures where degeneration is observed and the degeneration involves entire cells, with all of their processes. It has been suggested these non-competitive NMDA antagonists induce an increase in firing rate in a limbic circuit which includes the perforant pathway. At least some competitive NMDA antagonists induce the same pattern of degeneration and altered glucose utilization. There is anatomical and functional evidence that alterations in these same limbic structures are present in the dementia syndrome manifested by some schizophrenics and most Alzheimer's patients. This suggests that these non-competitive NMDA antagonists may provide a more complete model of psychoses and memory disturbances than previously recognized, in that they can mimic both persisting symptomatology and neuroanatomical abnormalities. While the neurochemical underpinnings of this effect remain elusive, it appears to be both age and sex dependent. Further studies of the mechanisms by which NMDA antagonists induce increased glucose utilization and neurotoxicity in these limbic structures may clarify these alterations in this simplified Papez-like circuit. PMID- 7795659 TI - Regulation of human protein C gene expression by the mouse WAP promoter. PMID- 7795660 TI - Progress in Drosophila genome manipulation. AB - The introduction of cloned and manipulated genetic material into the germline of an experimental organism is one of the most powerful tools of modern biology. In the case of the fruit fly, Drosophila melanogaster, there is also an unparalleled range of sophisticated genetic tools to facilitate subsequent analysis. In consequence, Drosophila remains a most favourable model organism for the dissection of gene structure and function in vivo. In this review we look at some of the achievements to date in Drosophila genome manipulation, and at what may be possible in the near future. PMID- 7795662 TI - In ovo transfection of chicken embryos using cationic liposomes. AB - It is reported that cationic liposomes are capable of transfecting embryos in unincubated fertile chicken eggs and that the cationic liposome, TransfectAce, has superior properties to Lipofectin. In order to determine the duration of expression of genes introduced in this way, embryos were transfected with an expression vector encoding the firefly luciferase cDNA under the control of the Rous sarcoma virus long terminal repeat (LTR). Luciferase activity could be observed consistently in day 3 embryos and activity was detectable up to day 8 of incubation. The relative expression of luciferase under the control of different viral promoters was compared in transfected chicken embryo fibroblasts and day 3 embryos. The cytomegalovirus immediate early promoter and the SV40 early promoter directed the highest amount of expression in fibroblasts while the Rous sarcoma virus LTR caused the highest amount of expression in embryos. Chicken embryo fibroblasts were transfected with the luciferase vector in order to examine duration of reporter gene expression in vitro. Luciferase expression was decreased exponentially over a 24-day period after which point luciferase activity could no longer be detected. These data suggest that stable integration of transfected DNA using liposomes is a rare event. Nevertheless, liposome mediated transfection of embryos is suitable for the examination of promoter activity in vivo and may be a useful method to transfect genes to study embryonic development. PMID- 7795661 TI - B-cell maturation in chimaeric mice deficient for the heat stable antigen (HSA/mouse CD24). AB - The murine differentiation marker heat stable antigen (HSA) is a GPI-anchored surface glycoprotein showing strong expression on immature B- and T-lymphocytes and gradually reduced expression during maturation. Although HSA has been suggested to be involved in adhesion and/or signalling, its function has not been clearly demonstrated so far. In order to elucidate the function of HSA, we analysed chimaeric mice that were generated by targeted disruption of both HSA alleles in ES cells. These mice contain normal numbers of peripheral B-cells and normal serum IgM and IgG titres of ES cell-derived allotype, demonstrating that HSA expression on B-cells is not an absolute requirement for their maturation. However, a reduction in immature B-cells in the bone marrow and an altered degree of bone marrow and blood chimaerism suggest that HSA expression influences the maturation of B-cells. PMID- 7795664 TI - Pharmacokinetics of cadmium following intravenous and oral administration to non lactating ewes. AB - In a preliminary study, ewes received daily oral cadmium chloride administrations and cadmium concentration was measured in blood and tissues. A pharmacokinetic analysis of cadmium disposition was then carried out in ewes administered cadmium chloride iv and, 21 months later, orally in the same ewes. Pharmacokinetic parameters were analysed using a 3-compartment open model. The systemic availability was 0.15-0.5%, the half-life of elimination was 100-150 d, the blood clearance was 0.12-0.16 l.kg-1.d-1 and the steady-state volume of distribution was 17-35 l/kg. Following iv administration cadmium was found in tissues about 2 years later. PMID- 7795663 TI - Production of transgenic mice by microinjection of DNA into vitrified pronucleate stage eggs. AB - Vitrification is a technique for cryopreserving cells without crystallization due to elevation of the viscosity during the cooling process. We have developed a rapid and convenient mean of cryopreserving mouse preimplantation embryos by vitrification using a solution (hereafter named DPS) consisting of 2.75 M dimethylsulfoxide, 2.75 M propylene glycol and 1.0 M sucrose. In vitro fertilized pronucleate stage eggs were used because a large number of stage-matched eggs can be obtained at once. Only successfully fertilized eggs were collected and vitrified in DPS. After warming, two DNA constructs were injected into a total of 257 cryopreserved eggs, of which 175 (68%) survived the injection and were transferred into six recipients. All recipients became pregnant and gave birth to a total of 20 pups. When these DNA constructs were concomitantly injected into fresh eggs, 18% of eggs that were transferred developed into live pups, which was the same as the 18% figure for the cryopreserved eggs. With respect to transgenesis, 40% of the pups (8/20) developed from vitrified eggs were transgenic. In terms of the injected eggs that had been transferred, 4.5% of the 213 fresh eggs and 3.1% of the 112 vitrified eggs developed into transgenic mice. These results indicate that the efficiency of production of transgenic mice from vitrified eggs is comparable to that from fresh eggs. PMID- 7795666 TI - Parasite nematode infections in Awassi adult sheep: distribution through Syrian farm flocks. AB - A survey was conducted on 1,474 adult sheep from 73 flocks distributed in the 13 provinces of Syria. Faecal egg and larval nematode outputs were studied. Marshallagia and Nematodirus infections were higher in the driest areas; infections by other nematodes, Dictyocaulus and small lungworms (Cystocaulus and Muellerius) were higher in the more rainy areas. A long transhumance limited small lungworm infections, which were higher in flocks using wet night shelters. PMID- 7795665 TI - Ginseng-enhanced oxidative and phagocytic activities of polymorphonuclear leucocytes from bovine peripheral blood and stripping milk. AB - This study investigated the effect of a dried ginseng extract on polymorphonuclear leucocytes (PMNL) in bovine blood and milk. In a test for chemiluminescence (CL), PMNL were pre-incubated in ginseng solution at 37 degrees C in 5% CO2 for 60 min, and then stimulated with bovine serum opsonized zymosan. The CL was about 30% higher for the cells pre-treated with ginseng solutions 100 1,000 micrograms/ml as compared with the non-ginseng-treated cells. In a test for phagocytosis, PMNL and fluorescent microspheres were incubated with ginseng in RPMI-1640 supplemented with 10% bovine serum at 37 degrees C for 60 min. The proportion of actively phagocytic cells in the ginseng-treated group was greater than that in the non-ginseng treated group. PMID- 7795667 TI - Disposition kinetics and dosage regimen of cefotaxime in cross-bred male calves. AB - The disposition kinetics and dosage regimen of cefotaxime were investigated in cross-bred calves following a single intravenous administration of cefotaxime (10 mg/kg). The elimination rate constant and elimination half-life were 0.273 +/- 0.060 h-1 and 3.48 +/- 1.17 h, respectively. The apparent volume of distribution (Vd area) and total plasma clearance were 3.51 +/- 0.66 l/kg and 0.81 +/- 0.10 l.kg-1.h-1, respectively. To maintain a minimum therapeutic concentration of 0.6 microgram/ml, a satisfactory intravenous dosage regimen of cefotaxime in calves should be 11 mg/kg followed by 9 mg/kg at 6 h. PMID- 7795668 TI - An alternative method for direct sequencing of PCR products, for epidemiological studies performed by nucleic sequence comparison. Application to rabbit haemorrhagic disease virus. AB - A sequencing strategy based on the use of commercially available fluorescent labeled universal primers for directly sequencing polymerase chain reaction (PCR) amplified material has been developed. The PCR reactions were performed with hybrid primers, specific to the viral sequence and possessing the sequence of the standard sequencing primers at their 5' end (M13 and reverse primers). These amplified fragments were sequenced by a classical dye-primer kit on an automated sequencer. As opposed to the use of fluorescent dideoxynucleotides, this sequencing method yielded accurate, high-grade sequences and had several advantages. First, the intensity of the sequencing peaks was much more homogeneous with the dye primer method. In addition, the problem of altered electrophoretic mobility, which may occur during the sequencing of custom synthesised fluorescent primers, was avoided. This method was successfully reproduced using several different sets of chimeric primers. We believe that it is suitable for epidemiological studies conducted by nucleic sequence comparison, as in the case of rabbit haemorrhagic disease virus, as well as in other systems. PMID- 7795669 TI - Changes in the coagulation profile of lambs intoxicated with aflatoxin in their feed. AB - Twenty-three male lambs were intoxicated with 2.5 ppm aflatoxins in their feed for a period of 3 weeks. Thirteen lambs were maintained as a control group (0 ppm aflatoxins in their feed). The coagulation profiles were determined from blood samples that were obtained at 0, 7, 14 and 21 d during the intoxication period and at 1, 2, 4 and 8 d of an 8-d clearance period. Aflatoxicosis in the animals was characterized by an increase in prothrombin time (P < 0.01) from d 14 of the intoxication period until the end of the experiment. An increase (P < 0.05) in fibrinogen concentration was detected beginning on d 21, instead of the expected decrease. This was probably due to the inflammation found in the lungs of the intoxicated animals. No difference in activated partial thromboplastin time was found between intoxicated and control animals. These results suggest that there was a significant change in some coagulation factors of the extrinsic pathway in the intoxicated lambs and that prothrombin time determination could be used as an indicator of aflatoxicosis in lambs. PMID- 7795670 TI - Vaccination and control of infectious and parasitic diseases. PMID- 7795671 TI - Veterinary vaccines. Specificities and the weight of regulations. PMID- 7795672 TI - [Vaccination in the sanitary and economic context of animal production]. PMID- 7795673 TI - [Vaccination of ruminants against brucellosis]. PMID- 7795674 TI - [Vaccination of swine against Aujeszky's disease]. PMID- 7795675 TI - Vaccination in fish. PMID- 7795676 TI - [Recombinant vaccine against rabbit hemorrhagic disease virus]. PMID- 7795677 TI - Defective adenoviruses as virus vectors for veterinary vaccines. PMID- 7795678 TI - [Pseudo-particles of rotavirus: properties and prospects of utilization]. PMID- 7795679 TI - [Proposed vaccination strategy agaist mastitis of dairy cows]. PMID- 7795680 TI - [Vaccination against abortive chlamydia infections of small ruminants]. PMID- 7795681 TI - [Vaccines against respiratory diseases of swine: example Mycoplasma hyopneumoniae]. PMID- 7795682 TI - Mucosal vaccination against toxoplasmosis. PMID- 7795683 TI - [Vaccination against avian coccidiosis]. PMID- 7795684 TI - Vaccination of rabbits against coccidiosis with precocious Eimeria lines. PMID- 7795685 TI - DNA-based immunization and the immune response to the hepatitis B surface antigen. PMID- 7795686 TI - Prospects in vaccine adjuvants. PMID- 7795687 TI - Vaccine delivery systems. PMID- 7795688 TI - Molecular events in production and transport of secretory IgA: a basis for design of reagents for passive immune protection. PMID- 7795690 TI - [Gastrointestinal flora and oral immunization]. PMID- 7795689 TI - [Lactogenic immunity and vaccinal protection in swine]. PMID- 7795691 TI - Epidemiology and vaccination strategy: Babesia divergens bovine babesiosis example. PMID- 7795692 TI - Powerhouse purchasing. PMID- 7795693 TI - Medical director raises barely a blip. PMID- 7795695 TI - Quality watch. Stroke rehab: all the right moves. PMID- 7795694 TI - How the Supreme Court saved NY hospitals $200 million. PMID- 7795696 TI - Riding the express. Is your subacute strategy on track? AB - For many health care providers, it's time to catch the bullet train called subacute care, an area of health care that's booming and offers new opportunity. But riding the rails of this new mode of transport isn't as easy as it seems. In fact, it can be downright tricky. That's why experts are warning hospital executives, in particular, to know beforehand exactly what they're getting into. PMID- 7795697 TI - If you want to play, you've got to pay. Community outreach is the name of the game, but how do hospitals pay for it? PMID- 7795698 TI - New wave equity. Surf's up for doctors as equity players. AB - For-profit capital is rushing into health care at an unparalleled rate. And a lot of it is finding its way toward physician groups and new combinations of physician-run organizations. It's true that hospital-based organizations understand the whys and wherefores of the new equity game. PMID- 7795699 TI - Tapping into teams. AB - Team management has a definite cachet in management circles in general industry; business magazines like Fortune regularly write about the concept, and executives in a wide variety of business fields are excited by it. But there's a lot of confusion behind the buzz, and the reality, say experts and those who've tried it, is a lot more complex than it might seem at first. Can the idea even be applied to hospitals and other large health care organizations? PMID- 7795701 TI - Winning CEOs. Score one for good coaching. Interview by Anne M. Nordhaus-Bike. PMID- 7795700 TI - Profiles in Service (1986-1995). 1993 Foster G. McGaw Prize winner. Cambridge Hospital, Cambridge, Massachusetts. PMID- 7795702 TI - Quality patrol. A front-line strategy. PMID- 7795703 TI - Doctors turned programmers. PMID- 7795704 TI - Clowning for comfort. Interview by Jim Montague. PMID- 7795705 TI - Managed care. Southern gumption. PMID- 7795706 TI - Long term care. Insurance for life. PMID- 7795707 TI - Restoring public trust. PMID- 7795708 TI - Transmembrane helix-helix interactions and accessibility of H2DIDS on labelled band 3, the erythrocyte anion exchange protein. AB - 4,4'-Diisothiocyanodihydrostilbene-2,2'-disulphonate (H2DIDS), a bifunctional inhibitor of anion exchange in erythrocytes, reacts with Lys-539 in band 3 at neutral pH and crosslinks to Lys-851 at alkaline pH. The accessibility of H2DIDS labelled band 3 was determined using an anti-H2DIDS antibody and proteolysis. Competitive enzyme-linked immunosorbent assays (ELISAs) showed that a polyclonal antibody raised against H2DIDS-labelled keyhole limpet hemocyanin bound a variety of stilbene disulphonates in the following order of affinities, H2DIDS having the highest affinity: H2DIDS > 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS) > 4-acetamido-4'-isothiocyanostilbene-2,2'disulphonate (SITS) > 4,4' dinitrostilbene-2,2'-disulphonate (DNDS) > 4,4'-diaminostilbene-2,2'-disulphonate (DADS). The antibody readily detected mono- or bifunctionally H2DIDS-labelled band 3 and proteolytic fragments on immunoblots. H2DIDS attached to Lys-539 is retained in a 7.5 kDa membrane-associated peptide after papain treatment of ghost membranes while the sequence around Lys-851 is more accessible. The band 3 proteolytic fragments protected by the membrane from proteolysis remained associated as a specific complex with a Stokes radius slightly smaller than the dimeric membrane domain after solubilization in detergent solution and retained 82% of the amino acid content of the membrane domain. Circular dichroism (CD) measurements of this H2DIDS-labelled complex showed that it had a very high helical content (86%). The loops connecting the transmembrane segments in H2DIDS labelled band 3 are therefore not required to maintain transmembrane helix-helix interactions. Denatured band 3 prelabelled with H2DIDS was more readily immunoprecipitated with the anti-H2DIDS antibody than was native band 3 in detergent solution. Deglycosylation of band 3 or proteolytic cleavage of the extramembranous loops did not enhance immunoprecipitation of H2DIDS-labelled band 3. The stilbene disulphonate inhibitor site is therefore relatively inaccessible and is bound by a bundle of helices in the native band 3 protein. PMID- 7795709 TI - The use of fluoresceinphosphatidylethanolamine (FPE) as a real-time probe for peptide-membrane interactions. AB - The characterization of fluoresceinphosphatidylethanolamine (FPE) as a real-time indicator of the electrostatic nature of a membrane surface is described. The conditions appropriate for the labelling of membranes and the implementation of FPE as a tool to monitor the interactions of various peptides with model membranes are outlined. It is shown that of the membrane-active peptides studied, Naja naja kaouthia cardiotoxin and pyrularia thionin bind to certain model membranes without insertion. Whereas the leader sequence of the nuclear encoded subunit IV of mammalian cytochrome c oxidase (E.C. 1.9.3.1), known as p-25, and melittin appear to bind and then partially insert into the membrane. It seems evident also that melittin does not adopt a fully transmembrane configuration. Melittin is known to promote membrane lysis and by employing a rapid-kinetic technique it is shown that the time-course of such lysis does not appear to correlate with peptide binding, but following binding a significant proportion of melittin must become inserted into the membrane before lysis appears to commence. PMID- 7795710 TI - Topological and segmental phylogenetic analyses of the anion exchanger (band 3) family of transporters. AB - Eleven sequenced anion exchanger (AE; band 3) proteins, including five AE1, four AE2 and two AE3 proteins, comprise the anion exchanger family (AEF) of homologous proteins. Eliminating the rat and rabbit proteins that are nearly identical to the corresponding mouse proteins, seven dissimilar members of this family were selected for study, divided into N-terminal, central and C-terminal segments (designated segments 0, 1 and 2, respectively) and analysed separately for sequence similarity and phylogenetic relatedness. Segments 0 are variable in length and sequence, are essentially lacking in some of the members of the AEF, and are not demonstrably homologous in other members of the family. All segments 1 and 2 are homologous, but they exhibit widely differing degrees of sequence divergence. Segments 2 are highly conserved in all AEF proteins. Segments 1 of the AE2 and AE3 proteins are as conserved as are segments 2, but segments 1 of the AE1 proteins have diverged from each other and from the AE2 and AE3 segments 1 much more than have segments 2 of these same proteins. The distributions of various types of amino acid residues in the putative transmembrane helical spanners of the seven dissimilar members of the AEF, based on a modification of the 14-spanner model of Wang et al. (1994) was determined, and this distribution was compared with those of other transmembrane transport proteins of known structure (bacterial rhodopsins, outer membrane porins of Gram-negative bacteria and bacterial photosynthetic reaction centres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795712 TI - Partitioning of 1,4-benzodiazepines into natural membranes. AB - The partition coefficients of several 1,4-benzodiazepin-2-ones (BZDs) were determined in a synaptosomal membrane-buffer system (Pm/b) by a two-component model analysis of the experimental data and the following values were obtained: flunitrazepam (FNTZ) = 32.2 +/- 1.5; diazepam (DZ) = 79 +/- 9; clonazepam (CNZ) = 30 +/- 4; nitrazepam (NTZ) = 38 +/- 2 and chlorodiazepoxide (CDZX) = 15.7 +/- 0.6. Correlations between these Pm/b and other chemical properties were performed by a principal component analysis. Hydrophobicity of BZDs, measured as the partition coefficients in different solvent systems, could be correlated with the presence of a methyl group at position 1 of the seven-member ring of the BZD molecule. The values of the partition coefficients of benzodiazepine in the synaptosomal membrane-buffer system were one order of magnitude lower than those obtained in an octanol-water or in ethyl acetate-water systems. The complexity of the membrane, unlike the isotropy of a pure solvent phase, provides a wide spectrum of types of interactions which, in turn, can be modulated in a dynamic manner by local or generalized changes in the lipid phase state. In that sense, the present values of Pm/b should be interpreted as an average tendency of BZDs to establish non-specific interactions with the molecules present in the different phases within biological membranes. Conversely, these Pm/b values reflect a consequence of the difference in complexity between natural membranes and the systems currently used as membrane models for drug partitioning. PMID- 7795711 TI - SecA-dependence of the translocation of a large periplasmic loop in the Escherichia coli MalF inner membrane protein is a function of sequence context. AB - We have analysed the translocation of a large periplasmic loop in the Escherichia coli MalF inner membrane protein when placed in different sequence contexts and under conditions when the function of the SecA protein is inhibited. The results show that the degree of SecA-dependence varies with sequence context: while translocation of the large loop in its normal context is only minimally affected by SecA inhibition, translocation is much more sensitive to SecA inhibition when the loop is placed in the context of other inner membrane proteins. Conversely, when the large MalF loop is replaced by segments from other proteins, translocation of those segments is again very sensitive to SecA inhibition. Thus, SecA-dependence is not an all-or-none phenomenon and is not only a simple function of, e.g. the length of a translocated segment or the hydrophobicity of the flanking transmembrane segments. PMID- 7795714 TI - NEUREX: a tutorial expert system for the diagnosis of neurogenic diseases of the lower limbs. AB - Specialist tutors have to transfer two types of knowledge to doctors who are specialising in a particular clinic: public declarative knowledge, including facts, notions, principles in that particular field; and their own private procedural knowledge acquired in years of direct experience. Embodying this knowledge into an expert system means that this information can be shared more rapidly, and tutoring is easier. This paper presents a tutorial expert system for neurological clinics which can emulate the diagnostic process of an expert neurologist for neurogenic diseases of the lower limbs, assist users in planning the optimal sequence of NG and EMG tests, interpret the results of these tests, and help users to achieve the most suitable diagnosis. PMID- 7795713 TI - Development and retrospective evaluation of Hepaxpert-I: a routinely-used expert system for interpretive analysis of hepatitis A and B serologic findings. AB - Hepaxpert-I is an expert system that interprets the results of routine serologic tests for infection with hepatitis A or B virus. The tests measure antibody to the hepatitis A virus (anti-HAV), IgM antibody to the hepatitis A virus (IgM anti HAV), hepatitis A virus (HAV) in the stool, hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), antibody to hepatitis B core antigen (anti-HBc and IgM anti-HBc), and hepatitis B envelope antigen (HBeAg) and antibody (anti-HBe). The knowledge base of Hepaxpert-I contains 13 If-Then rules for hepatitis A and 106 If-Then rules for hepatitis B serology. Formally, knowledge acquisition was done by forming a partition of each of the two sets of possible serologic finding patterns that contain patterns of serologic test results, 64 for hepatitis A and 4096 for hepatitis B, respectively. After entering an input pattern of serologic test results in Hepaxpert-I, a rule pattern matching algorithm based on indexing is internally employed as efficient access method for providing the respective interpretive text. Since 1 September 1989, Hepaxpert-I has been routinely applied at the Hepatitis Serology Laboratory of the 2nd Department of Gastroenterology and Hepatology at the University of Vienna Medical School (Vienna General Hospital). Beforehand, a retrospective evaluation of the expert system based on 23,368 hepatitis A and 24,071 hepatitis B serology requests was carried out. PMID- 7795715 TI - Evaluation of a knowledge-based decision-support system for ventilator therapy management. AB - Evaluation of knowledge-based systems differs from that of conventional systems in terms of verification and validation techniques. Furthermore, evaluating medical decision-support systems is difficult because the field is thus far comparatively unexplored. This paper presents an evaluation of a medical knowledge-based system called VentEx that supports decision-making in the management of ventilator therapy. Real patient data from 1300 hours of patient care involving 12 patients with 6 diagnoses are used to validate the knowledge base. The results range from 4.5% to 15.6% disagreement between the setting recommendations produced by VentEx and a gold standard, and 22.2% disagreement for recommendations for weaning. A comparison between the standard and two physicians showed that VentEx produced advice of the same quality as the physicians. PMID- 7795716 TI - Neural network assisted cardiac auscultation. AB - Traditional cardiac auscultation involves a great deal of interpretive skill. Neural networks were trained as phonocardiographic classifiers to determine their viability in this role. All networks had three layers and were trained by backpropagation using only the heart sound amplitude envelope as input. The main aspect of the study was to determine what topologies, gain and momentum factors lead to efficient training for this application. Neural networks which are trained with heart sound classes of greater similarity were found to be less likely to converge to a solution. A prototype normal/abnormal classifier was also developed which provided excellent classification accuracy despite the sparse nature of the training data. Future directions for the development of a full scale computer-assisted phonocardiographic classifier are also considered. PMID- 7795717 TI - Neural network classification of infrared spectra of control and Alzheimer's diseased tissue. AB - Artificial neural network classification methods were applied to infrared spectra of histopathologically confirmed Alzheimer's diseased and control brain tissue. Principal component analysis was used as a preprocessing technique for some of these artificial neural networks while others were trained using the original spectra. The leave-one-out method was used for cross-validation and linear discriminant analysis was used as a performance benchmark. In the cases where principal components were used, the artificial neural networks consistently outperformed their linear discriminant counterparts; 100% versus 98% correct classifications, respectively, for the two class problem, and 90% versus 81% for a more complex five class problem. Using the original spectra, only one of the three selected artificial neural network architectures (a variation of the back propagation algorithm using fuzzy encoding) produced results comparable to the best corresponding principal component cases: 98% and 85% correct classifications for the two and five class problems, respectively. PMID- 7795718 TI - Early history of venogenic impotence. AB - As early as 1860, innovative research defined the neural and vascular phenomena which generate male sexual tumescence. Sophisticated animal experiments provided important data about enhanced arterial inflow and occlusion of venous outflow which cause and maintain erection of the penis. On the basis of these observations, various treatment strategies for impotence, like sclerotherapy or surgical ligation to improve penile venous occlusion, have been attempted since 1873. In this historical review, I assert that contemporary theories of the role of penile venous occlusion during tumescence reiterate ideas proposed more than a century ago. PMID- 7795719 TI - Adenosine: a new agent in the diagnosis of impotence. AB - The haemodynamic effects of different dosages of adenosine were studied using colour flow Doppler sonography (CFDS) in 33 men, whose penile vascular bed responded well to papaverine. In six cases, we injected 25, 50, 100, 250 micrograms dosages of adenosine intracavernously at 15 min intervals and no erection occurred. However, 500 and 1000 micrograms doses of adenosine increased the arterial blood velocities for a few seconds in five cases. Later on, in eight cases, we infused 80 and 120 micrograms/kg/min adenosine for 3 min and only with 120 micrograms/kg/min dosage, did we observe clinical response and significant changes in CFDS parameters. Finally, 120 micrograms/kg/min adenosine dosage was infused for 10 min in 14 men and eight showed full erection while six had only tumescence. As adenosine was rapidly metabolized by adenosine deaminase, the erection lasted for only 5 to 13 min. No prolonged erection and no other side effect was observed. In addition no fibrosis and curvature was detected 6 months after the injections. We found that, in men, 10 min infusion of 120 micrograms/kg/min adenosine increased the arterial flow and to some extent venous resistance, resulting in full erection or tumescence. Therefore, adenosine may be used as an agent for the diagnosis of vasculogenic impotence, but further studies for determining the standard dosage of adenosine are needed. PMID- 7795720 TI - Characteristics of men interested in evaluation of erectile dysfunction. AB - Erectile dysfunction is a common disorder. However, not all dysfunctional men want to pursue evaluation. To delineate the characteristics of men interested in evaluation of erectile dysfunction, we conducted a mailed survey of 1031 randomly selected male veterans aged 30-99 years. We received 427 completed surveys. Using logistic regression, we found loss of sexual pleasure, loss of stiffness and duration of erection, and the ability to have orgasm to be predictors of which men were interested in evaluation of erectile dysfunction. Age, functional status, availability of a partner, marital status, sexual interest, partner's sexual interest, and duration of dysfunction were not significantly different between men interested and not interested in evaluation of erectile dysfunction. PMID- 7795721 TI - Minoxidil versus nitroglycerine: a prospective, double-blind, controlled trial in transcutaneous therapy for organic impotence. AB - Minoxidil (1 ml, 2% solution) has been tested against nitroglycerine (2.5 g, 10% ointment) and placebo in a prospective, double-blind controlled trial in transcutaneous therapy for organic impotence. A total of 116 patients participated in the study. Impotence aetiology breakdown was as follows: arterial, 61 cases; neurogenic, 34; arterial plus neurogenic, 12; venous leakage, 9. The application sites for treatment were: glans penis (minoxidil and placebo), penile shaft (nitroglycerine). All patients underwent through sexological counselling sessions (at outset and prior to subsequent changes in drug used). The results were considered positive if all symptoms of impotence (ie 'slow' erection, loss of erection, insufficient erection) were resolved; if even one symptom remained the results were considered negative. Side-effects were also considered. Minoxidil proved significantly more active than nitroglycerine which was, in turn, more effective than placebo. Minoxidil proved significantly more active in neurogenic impotent patients. Fewer side-effects were found with minoxidil than with nitroglycerine. These data lead one to consider minoxidil useful in the treatment of selected cases of organic impotence, as long as psychological conflict regarding sex and drug use are carefully removed. PMID- 7795723 TI - Visual sexual stimulation and penile vibration in screening men with erectile dysfunction. PMID- 7795722 TI - Assessment of local sympathetic function in patients with erectile dysfunction. AB - Fifty men with erectile dysfunction (ED) were urologically investigated for autonomic deficit by evaluation of the sympathetic skin response at the penis. They were additionally subjected to thorough urological, vascular, psychiatric and neurological examinations, and well-established neurophysiological tests of the somatosensory, sympathetic, and parasympathetic function. Patients with clinical evidence of neurological deficit showed abnormal results (68%) in at least one test of the autonomic nervous system. The sympathetic skin response at the penis was absent in 11 cases (37%) with clinical evidence of neuronal aetiology of the erectile dysfunction and was normal in all cases with positive evidence of a psychiatric origin of erectile dysfunction and no clinical indication of a neuronal deficit. Moreover, the sympathetic skin response at the penis was abnormal in three cases with normal results in the other neurophysiological tests. The results emphasize that the local sympathetic skin response at the penis is a useful extension of autonomic testing in ED patients since this method tests local sympathetic pathways and is sometimes the only evidence for autonomic deficit. From a clinical viewpoint, the sympathetic skin response at the penis is a very simple and time-saving neurophysiological method suitable for clinical routine and also for the investigation of outpatients. PMID- 7795724 TI - Tumours of the meninges: an overview of new entities. PMID- 7795726 TI - Immunostaining for calcineurin, a Ca2+/calmodulin-regulated protein phosphatase, in the diagnostic tumor pathology. AB - The present immunochemical study concerns the distribution of calcineurin (CaN), a Ca2+/calmodulin-regulated protein phosphatase, in the nervous and neuroendocrine systems of mammals, and discloses the CaN-immunostaining results of human neoplasms. CaN immunoreactivity (ir) was present throughout the nervous system with a marked regional variation in strength of the staining intensity. Light microscopic observations showed that CaN-ir was localized in neurons, but was not detected in non-neuronal cells including astrocytes. Ultrastructural study also revealed that CaN-ir was present only in neuronal elements such as somata, dendrites including postsynaptic densities and spines, and nerve terminals. CaN-ir was also detected in neuroendocrine cells of some endocrine tissues including the pineal gland, pituitary gland, adrenal grand, pancreas and thyroid gland. Immunostaining results of 107 surgical specimens of human neoplasms, including 9 cases of peripheral tumors, disclosed that CaN immunopositive tumor cells were found to be present in the neuronal tumors including neuroblastomas, ganglioglioma, ganglioneuroma, ganglioneuroblastoma, retinoblastomas, medulloblastomas and central neurocytomas. Also, some neuroendocrine tumors, such as pineocytomas, olfactory neuroblastomas and paragangliomas, specifically reacted for anti-CaN antibody. On the basis of these immunochemical findings, we have proposed that CaN can be a marker protein for detection of neuronal and neuroendocrine tumor cells in the diagnostic pathology of human neoplasms. PMID- 7795725 TI - Localization of apoptotic cells in situ of brain tumors. AB - The apoptotic cells in situ of normal tissues and human brain tumors were analyzed by the modified method of TUNEL, and the relationship between the localization of apoptotic cells and the expression of bcl-2 protein was examined. The localization of apoptotic cells in normal tissue was situated at fast renewing tissues, and differed from the localization of the expression of bcl-2 protein. In the cases of medulloblastoma, 7 out of 8 cases (87.5%) showed apoptotic cells. In contrast to the results of high frequency of apoptotic cells in medulloblastoma and germinoma, the expression of bcl-2 protein was found very low incidence in those tumors, which were thought to be sensitive against radiation or chemotherapy. These results suggested that the detection of apoptosis in situ by this method could predict the sensitivity of radiation or chemotherapy of the tumor cells. PMID- 7795727 TI - Clinicopathological study on pineocytoma. AB - Six cases of pineocytoma, which had developed in the parenchyma of the adult pineal body, were examined immunohistochemically and under an electron microscope, after the malignancy of each case had been determined using our classification. One case was rated as grade 1 showing a lobular structure and resembling the normal pineal body. Two cases were rated as grade 2 without a lobular structure but with pineocytomatous rosettes (P-rosettes). Two cases were rated as grade 3 without P-rosettes but with few mitotic figures. One case was rated as grade 4 with marked cellular pleomorphism, numerous mitotic figures and necrotic foci. When examined immunohistochemically, neuron-specific enolase was positive but glial fibrillary acidic protein was negative in all cases. Under an electron microscope, all cases showed abortive synapses, and clear or dense core vesicles. These findings allow us to make two conclusions. First, pineocytoma is always a tumor of neuronal lineage, regardless of their grade of malignancy. Second, the grade 4 pineocytoma should be distinguished from the type of tumor classically called "pineoblastoma." That is, the former seems to be a biologically dedifferentiated tumor, while the latter seems to be biologically undifferentiated tumor. PMID- 7795728 TI - The analysis of p53 tumor suppressor gene in pineal parenchymal tumors. AB - p53 gene mutation was examined in 9 pineal parenchymal tumors, 4 pineoblastomas and 5 pineocytomas, by the immunohistochemical and the polymerase chain reaction mediated single strand conformation polymorphism (PCR-SSCP) analyses. In each case, immunohistochemical analysis revealed no positive staining for p53 protein with either PAb1801 or DO-1 antibody and PCR-SSCP analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene. These findings suggested that p53 gene mutation is rarely related with the tumorigenesis of pineal parenchymal tumors. PMID- 7795729 TI - Hypothalamic hamartoma: anatomic, immunohistochemical and ultrastructural features. AB - Four patients with hypothalamic hamartoma were examined by CT and/or MR imaging, immunohistochemistry and electron microscopy. The hamartomas arose from the hypothalamus and extended inferiorly. LH-RH neurons were detected in three cases by immunohistochemistry. Electron microscopy revealed large myelinated axons, axon terminals containing dense-core vesicles and axon terminals with clear vesicles forming asymmetrical synapses. The development of hypothalamic hamartoma and its functional manifestations (precocious puberty and laugh attacks) are discussed in reference to the migration of LH-RH neurons from the olfactory placode. PMID- 7795730 TI - Clear cell (glycogen-rich) meningioma with special reference to spherical collagen deposits. AB - A detailed immunohistochemical and electron microscopic study of a case of clear cell (glycogen-rich) meningioma is presented. The neoplasm recurred three times and the patient died of the disease. The specimens obtained at all three operations showed similar basic histologic patterns. The tumor was comprised mainly of a syncytial, sheet-like proliferation of polygonal cells with clear cytoplasm containing abundant glycogen. The immunohistochemical features included epithelial membrane antigen- and vimentin-positive cytoplasm. The ultrastructural examination revealed distinctive meningocytic cells which contained large amounts of glycogen granules. In addition, the presence of numerous blocky, collagen conglomerations were a conspicuous feature of this tumor. The collagen deposits exhibited intensive immunopositivity for types I, III, IV and VI collagen, and their fine structure suggested the production of the extracellular matrix substance from the contiguous meningothelial cells with well developed Golgi complexes and frequent vesicles near the cell membrane. Proliferating cell nuclear antigen cell kinetics study revealed high labeling index of this neoplasm. The findings for this clear cell (glycogen-rich) meningioma may be useful in the differential diagnosis and treatment of this distinctive subtype of meningioma. PMID- 7795731 TI - Nuclear characterization and G2M ploidy in human brain tumors using semiautomated image analysis. AB - We used image analysis to study nuclear morphometry and DNA content in relation to time to tumor progression in a series of 88 patients with brain tumors. Clinical follow-up was obtained for 73 patients. The patients with diploid tumors had a longer time to tumor progression than those with triploid, tetraploid, or hypertetraploid tumors. Mean SG2M-DNA indices (DIs) increased significantly with a increase in mean DIs in all tumors. The mean DIs appeared to be dependent on the number of SG2M phase cells. We conclude that tumors with hypertetraploid in G2M ploidy are highly malignant. Those tumor cells have a large nuclear size, much deformity in nuclear shape, and great proliferative potential. The G2M tetraploid tumors showed a shorter time to tumor progression when the number of SG2M fractions was large. In contrast, the G2M-hypotetraploid tumors showed a longer time to tumor progression in comparison with other tetraploid and hypertetraploid tumors, but the difference was not significant. PMID- 7795732 TI - Immunohistochemical localization of the glucose transporter GLUT1 in choroid plexus papillomas. AB - Normal chroid plexus tissue and five choroid plexus papillomas were examined with antibody specific for the glucose transporter GLUT1, one isoform of facilitated diffusion glucose transporters, using the avidin-biotin-peroxidase complex (ABC) technique. GLUT1 in normal choroid plexus was localized at the basolateral plasma membrane of almost all epithelial cells. In three of five tumors, GLUT1 immunoreactivity was observed. A positive reaction was demonstrated at the plasma membrane of tumor cells. The number of GLUT1-positive cells was, however, much smaller than that of the normal choroid plexus. Our results suggest that GLUT1 expression in the choroid plexus is restrained during the course of transformation and that choroid plexus papilloma is composed of various differentiation tumor cells. PMID- 7795734 TI - Cytogenical analysis of brain tumors by FISH (fluorescence in situ hybridization) and FCM (flow cytometry). AB - In the present study, an analysis was made of chromosomal aberrations in brain tumors using the fluorescence in situ hybridization (FISH) technique. At the same time DNA histograms were obtained by flow cytometry (FCM) to make a comparative study of histological malignancy and prognosis. The subjects included 30 gliomas (7 of astrocytoma grade II, 15 of anaplastic astrocytoma (grade III), 8 of glioblastoma (grade IV)) and 26 meningiomas. In the study of FISH, DNA probes for chromosomes No. 7, 9, 10, and 17, were used to cause a reaction with chromosome No. 22 added for meningiomas. In the study with FCM, DNA index from DNA histogram was calculated using lymphocytes as the internal standard. In gliomas as a whole, chromosomes No. 7 and 17 showed high values, whereas, chromosomes No. 9 and 10 low values. Analysis by the grades of glioma showed that compared with gliomas of other grades, grade IV gliomas were higher for chromosome No. 17 and lower for chromosome No. 10. In meningiomas, while many cases showed a low value for chromosome No. 22, most cases of recurrent and atypical meningiomas showed a high value for chromosome No. 17. In gliomas, DNA index showed a correlation with the grade, and a positive correlation particularly with chromosome No. 17 in FISH. Recurrent and atypical meningiomas had a high DNA index. PMID- 7795733 TI - Histopathological study on the effect of octreotide. AB - The present investigation was performed to clarify the mechanism of action of octreotide. On a quantitative study by electron microscopy showed that lysosomes were markedly increased in the patients receiving octreotide. Growth hormone (GH) was shown to be in the secretory granules by the postembedding immunogold technique, but no GH immunostaining was noted of the lysosomes. The present investigation suggests that retention of secretory granules and subsequent lysosomal increase are the mechanism of GH-lowering effect of octreotide. PMID- 7795736 TI - Incidence of leukaemia and lymphoma in young people in the vicinity of the petrochemical plant at Baglan Bay, South Wales, 1974 to 1991. AB - OBJECTIVE: To determine whether there was an increased incidence of leukaemias and lymphomas in young people aged less than 25 years in the locality of a petrochemical plant at Baglan Bay, South Wales. METHODS: Geographical population based study to compare the observed and expected incidence of leukaemia and lymphoma with onset before the age of 25, in the years 1974 to 1991. The population was aged 0-24 years and lived within 1.5 and 3 km of the plant. The observed number of cases in various categories were compared with the expected numbers of cases calculated from the Welsh cancer registration rates. RESULTS: Although the observed numbers were generally greater than would be expected, none of the comparisons showed significant excess of leukaemias or lymphomas for any period of years. CONCLUSIONS: The study shows that the incidence of leukaemias and lymphomas in children and young people in the area around the BP Chemical site at Baglan Bay, South Wales, between the years 1974 and 1991 was not significantly greater than normal. PMID- 7795735 TI - Cancer incidence and mortality near the Baglan Bay petrochemical works, South Wales. AB - OBJECTIVES: To study incidence and mortality of leukaemias, cancer of the larynx, and other cancers near the petrochemical plant at Baglan Bay, in response to local concerns of an alleged cluster of cancers in the vicinity. METHODS: This is a small area study of cancer incidence, 1974-84 and of mortality, 1981-91 based on the national postcoded data held by the Small Area Health Statistics Unit and with population and socioeconomic data from the 1981 census. The study is centred on BP Chemicals Ltd, Baglan Bay, Port Talbot, West Glamorgan, South Wales and includes a general population sample of 115,721 people (1981 census) living within 7.5 km of the plant. Cancer incidence and mortality for all cancers, leukaemias, and cancer of the larynx were examined within 7.5 km and 3 km of the plant, and tests for decline in risk of these cancers with distance from the plant were carried out. Mortality from several other cancers possibly associated with the petrochemical industry was also studied. RESULTS: There were 5417 incident cancer cases and 2458 cancer deaths within 7.5 km of the plant during the periods of study. There was an 8% excess incidence of all cancers within 7.5 km, and a 24% excess of cancer of the larynx, consistent with a general excess of these cancers in West Glamorgan, but no apparent decline in incidence with distance from the plant, nor excess mortality. There was also no evidence of decline in leukaemia incidence or mortality with distance, at all ages or in children. Among the other causes included in the mortality study, there was an excess of multiple myeloma within 7.5 km, especially among women, and a significant decline in mortality from non-Hodgkin's lymphomas although there was no excess overall within 7.5 km. CONCLUSIONS: The apparent excess incidence of all cancers and cancer of the larynx within 7.5 km of the BP Chemical Ltd works was consistent with an excess more generally in West Glamorgan, possibly related, at least to some extent, to cancer registration in Wales. There was no excess mortality from these cancers. The results for multiple myeloma and especially non Hodgkin's lymphomas may have been chance findings in view of the multiple tests of significance carried out in the study. A study of lymphatic and haematopoietic cancers near oil refineries in Great Britain is to be undertaken that will help put the findings of the present study in wider context. PMID- 7795737 TI - Lead and cadmium in human placentas and maternal and neonatal blood (in a heavily polluted area) measured by graphite furnace atomic absorption spectrometry. AB - OBJECTIVE: To measure the concentrations of the trace elements lead and cadmium in human placenta and in maternal and neonatal (cord) blood. To assess the influence of the strongly polluted environment on the content of metals in tissues and on the permeability of placenta to cadmium and lead. Various methods of mineralisation were tested before analysis. METHODS: Graphite furnace atomic absorption spectrometry was used for the determination of lead and cadmium. The samples for analysis were prepared by mineralisation under pressure in a Teflon bomb (HNO3, 110 degrees C), by wet ashing under normal pressure (HNO3 + H2O2 for 12 hours), and by microwave digestion in concentrated nitric acid. RESULTS: In analysed samples the following mean concentrations of cadmium and lead were found: in venous blood Pb = 72.50 ng/ml, Cd = 4.90 ng/ml; in placenta Pb = 0.50 microgram/g, Cd = 0.11 microgram/g; in cord blood Pb = 38.31 ng/ml, Cd = 1.13 ng/ml. CONCLUSION: High concentrations of lead and cadmium were found in placentas and in maternal blood whereas in neonatal blood there was an increased concentration of lead and only traces of cadmium. It is concluded that the placenta is a better barrier for cadmium than for lead. Among the examined methods of mineralisation, microwave digestion was the best. PMID- 7795738 TI - Study of morbidity of personnel with potential exposure to vinclozolin. AB - OBJECTIVES: To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4 dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS: A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5 dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS: The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found. PMID- 7795739 TI - Mortality and cancer morbidity in workers from an aluminium smelter with prebaked carbon anodes--Part I: Exposure assessment. AB - OBJECTIVES: To design a job-exposure matrix for epidemiological studies of men who had worked in a Norwegian aluminium smelter between 1922 and 1975. METHODS: Jobs held by cohort members were identified from personnel records. Tasks and their locations were determined for all jobs, and information was gathered about changes in exposure conditions over time. The jobs were combined into categories thought to have experienced similar exposure conditions, and time weighted average exposures were estimated on a relative scale. The results were reviewed by a panel of former smelter employees and an experienced industrial hygienist. RESULTS: 96 different jobs could be identified from the cohort members' work histories. These were grouped into 18 categories, and relative exposure intensities were estimated for 31 different combinations of category and period. The most prevalent exposure in the cohort was pot emissions (fluorides, sulphur dioxide, and carbon monoxide; 74% ever exposed), followed by magnetic fields and heat stress (65-68%), asbestos (40%), and coal tar pitch volatiles (33%). CONCLUSIONS: Although the use of this job-exposure matrix in the subsequent epidemiological studies may result in some misclassification of exposure, this is unlikely to seriously attenuate true risks in a stratified analysis based on cumulative exposure. PMID- 7795740 TI - Mortality and cancer morbidity in workers from an aluminium smelter with prebaked carbon anodes--Part II: Cancer morbidity. AB - OBJECTIVE: To investigate associations between cancer incidence and exposure to coal tar pitch volatiles, asbestos, pot emissions (fluorides, sulphur dioxide), heat stress, and magnetic fields in workers from a Norwegian aluminium smelter that operated from 1914 to 1975. METHODS: Cancer incidence between 1953 and 1991 was recorded in a cohort of 1137 men hired between 1922 and 1975. The expected number of cancer cases was calculated from incidence rates in Norwegian men. A job exposure matrix with semiquantitative exposure estimates was used to investigate associations between cumulative exposure estimates was used to investigate associations between cumulative exposure and cancer incidence through exploring temporal relations by considering exposures only within specific time windows. RESULTS: A significant excess of cancer cases, 90 observed v 59.0 expected, was found in workers who had been employed for less than three years. No such excess was found in men with at least three years' employment, with 120 cases observed v 129.7 expected. In this subcohort an association was found between the incidence of bladder cancer and exposure to coal tar pitch volatiles 40 years or more before each person-year under observation, and between incidence of lung cancer and tar exposure 35-50 years before observation. An association was also found between incidence of kidney cancer and exposure to heat stress 20 35 years before observation. CONCLUSIONS: The results support previous findings that exposure to coal tar pitch volatiles in the aluminium industry has been associated with increased risk of bladder and lung cancer. They also add information about temporal relations, suggesting that exposure to tar in this smelter has acted on an early stage in the development of these cancers, followed by a latency period of 30-40 years. PMID- 7795741 TI - Mortality and cancer morbidity in workers from an aluminium smelter with prebaked carbon anodes--Part III: Mortality from circulatory and respiratory diseases. AB - OBJECTIVE: To investigate associations between exposure to pot emissions (fluorides, sulphur dioxide) and mortality from chronic obstructive lung disease, coal tar pitch volatiles and mortality from diseases related to atherosclerosis, and carbon monoxide and mortality from ischaemic heart disease. METHODS: Mortality between 1962 to 1991 was investigated in a cohort of 1085 men hired by a Norwegian aluminium smelter between 1922 and 1975. Associations between cumulative exposure and mortality were investigated through SMR analysis based on national mortality rates; temporal relations were explored by considering exposures only within specific time windows. Circulatory mortality was also investigated by Poisson regression analysis. RESULTS: There were 501 deaths v 471.3 expected in the cohort. The excess was confined to short term workers and did not seem to be associated with exposures in the smelter. Analysis of mortality among the 661 men with at least three years employment showed associations between cumulative exposure to tar 40 years before observation and atherosclerotic mortality (P = 0.03), and between exposure to pot emissions 20-39 years before observation and mortality from chronic obstructive lung disease (P = 0.06). No association was found between exposure to carbon monoxide and mortality from ischaemic heart disease, but cerebrovascular mortality was associated with exposure to pot emissions (P = 0.02). Results for atherosclerotic and cerebrovascular diseases were confirmed through Poisson regression analysis. CONCLUSIONS: The data support previous findings of increased mortality from ischaemic heart disease in workers exposed to tar, and some support is also provided for earlier reports of increased respiratory mortality in potroom workers. PMID- 7795742 TI - Chest radiography and high resolution computed tomography in the evaluation of workers exposed to silica dust: relation with functional findings. AB - OBJECTIVES: To compare the usefulness of high resolution computed tomography (HRCT) with chest radiography (CR) in the diagnosis and assessment of severity of silicosis. METHODS: 27 workers exposed to silica underwent CR, HRCT, and pulmonary function tests. Two experienced readers independently evaluated CR by International Labour Office classification, and grouped the results into four categories. HRCT categories of nodule profusion and the extent of emphysema were graded on a four point scale; in 20 subjects the percentage distribution of lung densities were measured by HRCT. RESULTS: Concordance between readers was higher for HRCT than for CR (K statistic = 0.49 and 0.29 respectively). There was poor concordance between CR and HRCT in the early stage of silicosis. No significant difference in pulmonary function tests was found among different CR categories, but forced expiratory volume in one second (FEV1), maximal expiratory flow at 50% and 75% of FVC (MEF50, MEF75), and diffusion capacity significantly decreased with increasing HRCT categories. Subjects with simple silicosis detected by HRCT had a lower FEV1 than subjects without silicosis, whereas subjects with conglomerated silicosis showed higher residual volume and functional residual capacity than subjects with simple silicosis. These relations were not affected by smoking or symptoms of chronic bronchitis. Different grades of emphysema detected by HRCT were significantly different in diffusion capacity. Only the HRCTs of the lowest and the highest categories of profusion of parenchymal opacities were significantly different in their distribution of density classes. CONCLUSION: HRCT is more reproducible and accurate than CR, as suggested by the higher agreement between readers and the better correlation with pulmonary function tests, irrespective of smoking and chronic bronchitis; however, these data do not support the hypothesis that HRCT is more sensitive than CR in the early detection of silicosis. PMID- 7795743 TI - Byssinosis in Guangzhou, China. AB - OBJECTIVES: To study the prevalence of byssinosis and other respiratory abnormalities in workers exposed to cotton dust in Guangzhou in two factories that processed purely cotton. METHODS: All the 1320 workers exposed were included. The controls were 1306 workers with no history of occupational dust exposure. Total dust and inhalable dust were measured by Chinese total dust sampler and American vertical elutriator respectively. A World Health Organisation questionnaire was used. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured by a Vitalograph spirometer. RESULTS: The median inhalable dust concentrations ranged from 0.41 to 1.51 mg/m3 and median total dust concentrations from 3.04 to 12.32 mg/m3. The prevalence of respiratory abnormalities in the cotton workers were (a) typical Monday symptoms 9.0%; (b) FEV1 fall by > or = 5% after a shift 16.8%; (c) FEV1 fall by > or = 10% after a shift 4.2%; (d) FEV1 < 80% predicted 6.1%; (e) FEV1/FVC < 75% 4.0%; (f) cough or phlegm 18.2%; (g) chronic bronchitis 10.9%; and (h) byssinosis, defined by (a) plus (b) 1.7%. With the exception of (d), most of the prevalences increased with increasing age, duration of exposure, and cumulative inhalable dust exposure. No increasing trends of respiratory abnormalities were found for current total dust, inhalable dust, and cumulative total dust concentrations. Compared with controls, after adjustment for sex and smoking, with the exception of (d), all the pooled relative risks of respiratory abnormalities were raised for cotton exposure. CONCLUSION: It is concluded that cumulative inhalable cotton is likely to be the cause of byssinotic symptoms, acute lung function decrements, cough, or phlegm, and chronic bronchitis. PMID- 7795744 TI - Evaluation of the respiratory health of dock workers who load grain cargoes in British Columbia. AB - OBJECTIVES: To investigate the respiratory health of dock workers who load grain cargoes. METHODS: The respiratory health of 118 dock workers who load grain cargoes in the ports of Vancouver and Prince Rupert was compared with that of 555 grain elevator workers from the same regions. 128 civic workers were used as an unexposed control group. RESULTS: The prevalences of chronic cough and phlegm were at least as high in dock workers as those found in the elevator workers, and when adjusted for differences in duration of employment and smoking, dock workers had an eightfold higher risk of developing chronic phlegm than did civic workers. Symptoms of eye and skin irritation that were experienced at least monthly were highest for dock workers. Average percentage of the predicted FEV1 and FVC for dock workers (mean 100.6% and 105.3% respectively) were similar to the civic workers but significantly higher than those found for elevator workers. Higher subjective estimates of duration of exposure to grain dust (hours/day) were associated with lower values of FEV1. CONCLUSIONS: The more intermittent grain dust exposure patterns of dock workers may have allowed for some recovery of lung function, but chronic respiratory symptoms were less labile. PMID- 7795745 TI - Pre-employment screening among trainee bakers. AB - OBJECTIVES: To assess the prevalence of atopy in a vocational school so as to evaluate the feasibility of pre-employment screening. METHODS: The prevalence of atopy by family diathesis, prick tests, immunoglobulin E (IgE) concentrations, and personal history of allergic respiratory diseases was investigated in 144 trainee bakers and 81 students on a graphic artists course (mean age 15.4 years). Skin sensitisation to wheat, rye, and barley flours, to alpha amylase, and to storage mites was also evaluated. RESULTS: Personal allergic symptoms were reported by 13.2% of the bakers and 14.7% of the graphic artists and there was a significant association between symptoms and atopy by prick tests (odds ratio (OR) 17.2; 95% confidence interval (95% CI) 5.27-56.4) and by family history (OR 3.11; 95% CI 1.02-9.53). When bakers were grouped according to the presence of allergic symptoms and results of immunological tests, 6.9% had asthma, 6.3% had rhinoconjunctivitis, and a high percentage (28.5%) were without symptoms but scored positive on prick tests or family symptoms. Skin sensitisation to storage mites had similar prevalences (16%) in the two groups of trainees and occurred nearly always in atopic people. Positive skin tests to wheat flour (3.5%), rye (0.7%), and alpha amylase (0.7%) were specific to bakers. CONCLUSIONS: Pre employment screening is a useful source of medical information and allows for counseling. The presence of asthma, or of another allergic disease in a severe form, is suggested as a criterion for excluding students of a vocational school from training as bakers. Student bakers without allergic symptoms but atopic by other criteria should be informed about their risks of developing occupational asthma, and periodic check ups must be recommended. Screening studies in vocational school provide a better understanding of specificity of skin sensitisation to occupational allergens. PMID- 7795747 TI - Assessment of risk of lung cancer among mild steel and stainless steel welders. PMID- 7795746 TI - Sex ratio of offspring of men exposed to sodium borates. PMID- 7795748 TI - Urinary N-acetyl-beta-D-glucosaminidase (NAG) and exposure to inorganic lead. PMID- 7795749 TI - Cause of occupational disease. AB - The concept of causality is reviewed with special emphasis on occupational diseases. Separate approaches from the philosophical, scientific, and legal points of view are identified. There is controversy over the methodology of logical causality; inductive and deductive methods are described and reference is made to the verification or refutation approach. Application of the methods to epidemiology are reviewed. It is likely that many diseases have multiple causes and that only a component of occupational causality can be identified in each patient. Methods of assigning such a component are discussed. The difficulties of developing an equitable compensation policy in such circumstances are reviewed. The possible benefits of proportional compensation are noted. PMID- 7795750 TI - Developments in reproductive risk management. AB - Internationally, the debate on aims for occupational health policy is expanding its horizons. Included among the issues are not only concerns about safety for workers, but also for their progeny. Equality among the sexes is also assuming a prominent position. In several countries, existing and proposed legislation already considers these matters. In the course of this article it is argued that this legislation and its implementation are inadequate. There are several reasons for this. Firstly, what constitutes health risks for workers exposed to chemical substances is subject to different interpretations. This is further complicated when one includes risks to reproductive function and to the progeny: the reproductive risks of toxicity. The different interpretations of the concepts of safety and equality are also discussed. There are differences in regulations and in standards about whether or not safety factors should be used when knowledge is uncertain. The operation of reasonable measures with a generic or sex specific policy also differs. Secondly, the current occupational exposure limits are set too high. These aspects are considered and it is probable that the policy aims should be made more specific. An elaborated approach that includes the "precautionary principle" in safety standards is proposed. To advise employers in their role as managers of reproductive risks of toxicity, a recently developed system for occupational health and safety services is described. This system is based on two criteria: effectiveness and reasonableness of proposed measures. The effectiveness criterion includes the precautionary principle; the reasonableness criterion includes equal rights and opportunities for men and women. Finally, a supportive governmental policy that is consistent with the most recent international development is recommended. PMID- 7795751 TI - Implementation of the precautionary principle in standards for the workplace. AB - The objectives were to describe and discuss the current and proposed European occupational health policy on two categories of substances that pose serious effects: those potentially carcinogenic or genotoxic and those with toxic effects on reproduction. The precautionary principle was applied to setting standards for the workplace for those two categories of substances, to give an impression of the resulting limit values and the consequences of the implementation of this precautionary principle. A pragmatic approach was chosen as this starts with substantial indications of health risks. For the suspected carcinogenic or genotoxic substances 0.1 mg/m3 as a precautionary occupational exposure limit (precautionary OEL) is proposed. For the substances suspected of causing reproductive toxicity the precautionary OEL was derived in three ways, depending on the availability of data and of a current Dutch workplace standard (MAC, maximum accepted concentration): (a) by calculation based on available inhalatory animal data on the risks of reproductive toxicity; (b) by adding a safety factor of 10 to the current MAC, if no inhalatory animal data on reproductive toxicity are available; (c) by using 0.1 mg/m3 as precautionary OEL for substances suspected of having reproductive toxicity but without inhalatory animal data on reproductive toxicity and without a MAC. PMID- 7795752 TI - Physical work load and gestational age at delivery. AB - OBJECTIVE: To assess the impact of physical activity on the gestational age at delivery in women performing physical tasks in their jobs during pregnancy. METHODS: Qualified nurses at 15 weeks of pregnancy were asked through a questionnaire to describe the tasks in their regular job, the physical activities involved, and their exposure to other occupational stressors. The physical activities to be identified were walking, standing, lifting, stooping, squatting, and sitting. RESULTS: A high degree of daily physical work load during pregnancy seemed to be a significant predictor for the gestational age at delivery, whereas chemical and infectious agents were not. CONCLUSIONS: Physical work load during pregnancy should be diminished to avoid adverse effects on gestational age at delivery. PMID- 7795753 TI - Tumour necrosis factor-alpha (TNF-alpha) in patients who have asbestosis and develop cancer. AB - OBJECTIVES: Concentrations of tumour necrosis factor-alpha (TNF-alpha) were assayed by radioimmunoassay in serum samples collected between 1981 and 1987 from 111 patients with asbestosis who were at a high risk of cancer. Follow up of these patients until 1993 showed that 38 had developed cancer (27 lung, three mesotheliomas, and eight diverse malignancies). RESULTS: The mean serum concentrations of TNF-alpha given in fmol/100 microliters serum in all the cases with cancer (14.1) and the cases with lung cancer (13.6) were significantly higher (P < 0.05) than the mean concentrations in the exposed controls (10.5). A positive increase was considered to be any value that was > 2 SDs above the mean of the exposed controls. 22% (six of 27) of the cases with lung cancer were positive compared with 4% (three of 73) of the exposed controls, a significant difference (P < 0.001). The serum concentrations of TNF-alpha correlated moderately with cancer (r = 0.3), lung cancer (r = 0.3), and Neu oncoproteins and epidermal growth factor receptor (EGFR) (r = 0.3, 0.5 respectively). Also, there was a significant correlation between development of cancer and severity or progression of asbestosis. There was no correlation between the concentrations of TNF-alpha and severity or progression of asbestosis. CONCLUSIONS: These results showed high concentrations of TNF-alpha in the patients who had cancer. TNF-alpha may offer an auxiliary method in early diagnosis of cancers related to asbestosis. PMID- 7795754 TI - Exposure to styrene and chronic health effects: mortality and incidence of solid cancers in the Danish reinforced plastics industry. AB - OBJECTIVES: To study the occurrence of non-malignant diseases and solid cancers in workers exposed to styrene in the Danish reinforced plastics industry. METHODS: All 36,610 workers of 386 reinforced plastics companies and 14,293 workers not exposed to styrene from similar industries were followed up from 1970 to 1990. This industry is characterised by simple exposure conditions, exposure to high concentrations of styrene, and a high proportion of small companies, and the exposure assessment was based on experts' classification on a company level. The mortality from non-malignant causes and the incidence of solid cancers were compared with the national rates. Poisson models were used for internal comparisons. RESULTS: A total of 3031 deaths and 1134 newly diagnosed cases of solid cancer were reported in the workers in the reinforced plastics industry. In companies where 50% or more of the workers produced reinforced plastics an increased mortality rate ratio (MRR) for degenerative disorders of the nervous system (multiple sclerosis, parkinsonism, and motor neurone disease; MRR 1.8, 16 cases, 95% confidence interval (95% CI) 0.9-3.8) and an increased incidence rate ratio (IRR) for pancreatic cancer (IRR 2.2, 17 cases, 95% CI 1.1-4.5) was found. For both disease categories increased occurrence was also found among long term workers, workers of the 1960s (the period with the highest exposure to styrene), and workers with a latent period of more than 10 years after the start of employment. No other non-malignant diseases or solid cancers showed these patterns. CONCLUSION: The findings have to be interpreted with caution, due to the company based exposure assessment, but the possible association between exposures in the reinforced plastics industry, mainly styrene, and degenerative disorders of the nervous system and pancreatic cancer, deserves attention. PMID- 7795755 TI - Longitudinal study of the health of cotton workers. AB - OBJECTIVES: To follow up a group of newly employed workers in a cotton mill, and to report changes in symptoms over time. METHODS: A group of 110 mill workers at a cotton mill in Shijiazhuang, China, was investigated by questionnaire, skin testing, and spirometric measurements of airway responsiveness through forced expiratory volume in one second (FEV1). The workers were examined before starting work, at 10 weeks, and at one year. RESULTS: Decreases in FEV1 over shifts were small at 10 weeks and one year, and slightly higher among people with skin reactions to cotton dust extracts. Airway responsiveness, defined as the average decrease in FEV1 after 1.25 mg methacholine was increased at 10 weeks. It remained about the same after one year, except in the workers positive for the skin test, in whom it was further increased. Subjective symptoms of chest tightness and cough with phlegm increased progressively at 10 weeks and one year; nasal irritation remained unchanged and dry cough decreased between 10 weeks and one year. CONCLUSION: The results suggest that the airway inflammation caused by cotton dust increases with increasing exposure time and that the changes are more notable in workers with reactivity to cotton dust extract. PMID- 7795756 TI - Dose-response relation between exposure to two types of hand-arm vibration and sensorineural perception of vibration. AB - OBJECTIVES: 31 railway workers and 32 lumberjacks were examined to compare the dose-response relation between the exposure to two types of hand-arm vibration and the sensory disturbances in peripheral nerves as evaluated by the vibration perception thresholds (VPTs). METHODS: Clinical examinations were carried out that included measurements of the VPTs, and electroneuromyography (ENMG), and an inquiry to confirm the use of vibrating tools. Diseases of the central nervous system and neuropathies were checked by inquiry and a clinical examination, diabetes was excluded by a blood sample analysis, and the subjects with carpal tunnel syndrome confirmed with ENMG were excluded from the study. RESULTS: Lifetime use of hand held tamping machines (railway workers) and chain saws (lumberjacks) had a significant correlation with the VPTs at frequencies from 32 to 500 Hz. The increase of the VPTs (250 Hz) in relation to use of vibrating tools was 1.8-fold higher on average in the whole group and 2.3-fold higher in the young (< 45) railway workers who had used hand held tamping machines, than in the corresponding groups of lumberjacks, who had used chain saws, whereas the frequency weighted acceleration of vibration in tamping machines was fourfold. CONCLUSION: There was a significant dose-response relation between the exposure to hand-arm vibration and the VPTs. The VPTs as a function of the frequency weighted acceleration of vibration and the exposure to vibration gave promising results for assessment of the risk of damage to sensory nerves induced by vibration. PMID- 7795757 TI - Ocular effects of exposure to triethylamine in the sand core cold box of a foundry. AB - OBJECTIVES: To assess the acute and chronic ophthalmological effects of triethylamine exposure among foundry workers. METHODS: Ocular effects on people currently, previously, and never exposed to triethylamine in a foundry cold box were studied at two points in time. The initial phase included an ocular examination with a slit lamp to assess corneal health, a visual acuity test, and a questionnaire to assess vision symptoms. The follow up included measurements of corneal thickness with an ultrasonic pachymeter and the vision symptoms questionnaire before and after the shift and at the beginning and end of the week. Personal air measurements for triethylamine were also obtained during the follow up. RESULTS: The vision symptoms of blurriness, halos around lights, and blue hazy vision occurred more often in currently exposed workers than those previously or never exposed to triethylamine. Air concentrations of triethylamine ranged from < 0.33 mg/m3 to 20.3 mg/m3. Among currently exposed workers, symptoms were more common among those with exposure to > 10 mg/m3 of triethylamine (odds ratio (OR) = 3.0, 95% confidence interval (95% CI) 0.35-25.6). No differences in corneal thickness were found in currently or previously exposed workers and those never exposed. No increase in corneal thickness was found after v before the shift. CONCLUSION: Despite low concentrations of triethylamine and no corneal oedema, workers exposed to triethylamine reported vision symptoms. Possible explanations for these symptoms without corneal oedema are that triethylamine affects ciliary muscle function or that the corneal oedema was transient and not present when corneal thickness measurements were taken. No chronic effects were found in previously exposed workers. Further research is needed to elucidate the mechanism for the reported vision symptoms, which occurred below the current United States eight hour time weighted standard of 100 mg/m3 and the American Conference of Governmental Industrial Hygienists (ACGIH) recommended value at the time of our study of 40 mg/m3. We recommend that air concentrations be maintained to meet the current recommended ACGIH threshold of 4.1 mg/m3. PMID- 7795758 TI - Physiologically based pharmacokinetic model for acetone. AB - OBJECTIVE: This study aimed to develop a physiologically based pharmacokinetic model for acetone and to predict the kinetic behaviour of acetone in the human body with that model. METHODS: The model consists of eight tissue groups in which acetone can be distributed: the mucous layer of the inhaled air tract, the mucous layer of the exhaled air tract, a compartment for gas exchange (alveolus of the lung), a group of blood vessel rich tissues including the brain and heart, a group of tissues including muscles and skin that have low perfusion rates, a group of fatty tissues, an organ for metabolism (liver), and a compartment for urinary excretion (kidney). A mucous layer in the model is only the outermost layer of the mucus lining the wall of the air tract during inhalation and exhalation. To check the relevance of the model, the simulated results were compared with the experimental data. Next, simulation was conducted by changing the volume of the mucous layer and the respiratory rate to clarify the effect of these variables. Finally, simulation of an occupational situation was performed. RESULTS: With an appropriate value for the volume of mucous layer, the simulated acetone concentrations in arterial blood, end exhaled air, urine, and fatty tissue were found to agree well with the experimental data. The volume of mucous layer and rate of respiration were critical for the appropriate simulation. The simulated occupational situation fitted the observed regression line in field studies quite well. The simulation also enabled predictions to be made about the characteristic kinetics for water soluble solvents. CONCLUSION: The model is useful for understanding and explaining the kinetics of acetone. PMID- 7795760 TI - The Jones criteria for guidance in the diagnosis of rheumatic fever. Another perspective. PMID- 7795759 TI - Upper airway response in workers exposed to fuel oil ash: nasal lavage analysis. AB - OBJECTIVES: Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS: A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS: Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION: A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash. PMID- 7795761 TI - Guideline maintenance and revision. 50 years of the Jones criteria for diagnosis of rheumatic fever. AB - OBJECTIVE: To understand better the factors that led to revisions of the Jones criteria, a widely used diagnostic guideline for diagnosis of rheumatic fever. DESIGN: The original publication of the Jones criteria and the four revisions were examined to identify changes. A computer software maintenance paradigm was applied, and modifications were categorized as corrective (error correction), perfective (enhancements in response to user needs), or adaptive (responses to new knowledge). RESULTS: Modifications of the Jones criteria were primarily corrective and perfective. Disease characteristics, originally characterized as major manifestations, were subsequently categorized as minor manifestations and vice versa. Twenty years after the initial publication, a requirement was added to enhance specificity (evidence for antecedent streptococcal infection). Descriptions of rheumatic manifestations became more detailed over time to eliminate ambiguous definitions and provide information to help clinicians decide about borderline cases. This emphasis on corrective and perfective maintenance contrasts with an expectation that adaptive changes would predominate, as with most knowledge-based systems. In fact, despite 50 years of technologic and methodologic advances in medicine, only echocardiography and new antibody testing contributed new knowledge that bears on the diagnosis of rheumatic fever. CONCLUSIONS: Corrective and perfective maintenance can be avoided by making effective use of knowledge that exists at the time a guideline is published. Despite the apparent durability of the Jones criteria, carefully structured, evidence-based guidelines should require less corrective and perfective maintenance. Adaptive maintenance can be anticipated if the quality of evidence or the level of consensus that supports each recommendation is explicitly recorded. PMID- 7795763 TI - The Pediatric Symptom Checklist. Support for a role in a managed care environment. AB - OBJECTIVES: To gather data based on studies of the Pediatric Symptom Checklist, identify risk factors associated with high levels of dysfunction in primary care pediatric settings, and explore the relationship between common risk factors and psychosocial problems identified by pediatricians. DESIGN: Retrospective review and cross-sectional, case-referent survey. SETTING: Subjects were selected from three primary care pediatric clinics in Massachusetts: a private practice in a predominantly white, middle-class suburb, an urban health maintenance organization clinic, and an inner-city clinic. PARTICIPANTS: Of 423 outpatients aged 6 to 12 years screened for psychosocial problems, 72 children and their families were seen for in-depth structured and clinical interviews (24 from each site). INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Children with a single parent and/or those who were economically disadvantaged were significantly more likely to show psychosocial impairment. The specificity of the Pediatric Symptom Checklist was 100% in samples with a lower socioeconomic status compared with 68% in middle-class samples, and sensitivity was 95% in middle-class samples compared with 80% in lower-class samples. Pediatricians identified psychosocial problems in eight of 15 children with a history of familial mental illness or substance abuse and seven of eight children with a history of physical or sexual abuse, but only six of 17 cases from single-parent families and four of 11 cases from poor families. CONCLUSIONS: Pediatricians should be sensitive to psychosocial dysfunction especially in single-parent and low-income families. Use of the Pediatric Symptom Checklist for psychosocial screening in a managed health care delivery system could target capitated resources efficiently by providing early identification and secondary prevention of psychosocial morbidity. PMID- 7795762 TI - Relation of alcohol expectancies to changes in problem drinking among college students. AB - OBJECTIVE: To evaluate the relation between alcohol expectancies and problem drinking during 3 years of college. DESIGN: Cohort with 3-year follow-up. SETTING: Private university campus. PARTICIPANTS: A random sample of 260 students entered a longitudinal study of alcohol use at the beginning of their freshman year. One hundred eighty-four students completed follow-up measures at the end of their junior year. Respondents were 90% white, with a mean (+/-SD) age of 17.9 +/ 0.5 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: A standardized measure of expectations and subjective evaluations of outcomes associated with drinking, quantity and frequency of alcohol use, and a composite measure of alcohol-related problems. RESULTS: Students were divided into nondrinking, low-risk, and high risk groups for problem drinking. A repeated-measures multivariate analysis of variance indicated significant interaction effects for risk group by expectancy scale (P < .009) and for expectancy scale by time (P < .001). The three risk groups differed significantly from each other on positive outcome expectations at entry into college and positive expectations and negative outcome evaluations at the end of the junior year. Students who became problem drinkers during college had significantly higher positive outcome expectation scores at both times and developed less concern for negative outcomes by the end of their junior year. The few initial problem drinkers who moderated their drinking during college demonstrated an increased concern for negative outcomes by their junior year. CONCLUSIONS: Alcohol expectancies are associated with differing patterns of alcohol use and are longitudinally related to subsequent changes in alcohol use and problem drinking. PMID- 7795764 TI - Stress in pediatric faculty. Results of a national survey. AB - OBJECTIVES: To determine current levels of pediatric faculty stress experienced by pediatric faculty and to examine contributors to and consequences of this stress. DESIGN: Random survey, using attitude questionnaire. SETTING: Twenty-six medical school-based pediatric programs nationwide. PARTICIPANTS: Two hundred fifty-two full-time pediatric faculty members. MAIN OUTCOME MEASURES: Stress level; importance of specific sources of stress and fulfillment; satisfaction with time allotted to various activities; social support; satisfaction with career choices. RESULTS: The return rate was 64%. Forty-six percent of respondents reported "high" or "very high" levels of usual stress; 64% were stressed beyond a "comfortable" level at least "frequently." Women (P < .05), assistant or associate professors (P < .001), and faculty on the tenure track (P < .006) reported feeling "overstressed" more often. Major sources of stress were pressure to do research, family needs (48%), and lack of personal time (40%). About half (51%) agreed that the recent emphasis on reducing resident stress has led to increased pressure on faculty members. Frequency of feeling overstressed was reduced if respondents felt valued by their chairperson (P < .001) and by other faculty (P < .01). Within the last year, 47% had considered moving to another medical school. Another 43% had considered leaving academia. The more frequently the respondent felt overstressed, the more likely he or she was to have considered such changes (P < .001). CONCLUSIONS: The stress currently experienced by pediatric faculty is substantial and seems to affect long-term commitment to academic medicine. Creative solutions to this issue should be explored. PMID- 7795765 TI - Relationship of infant feeding to recurrent wheezing at age 6 years. AB - OBJECTIVES: To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses. DESIGN: Prospective, longitudinal study of healthy infants followed up from birth to 6 years of age. SETTING: Nonselected health maintenance organization population in Tucson, Arizona. PARTICIPANTS: There were 1246 healthy infants enrolled at birth, 988 of whom had data on both infant feeding and wheezing at age 6 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recurrent wheeze (four or more episodes in the past year) was assessed by a questionnaire that was completed by parents when the children were 6 years old. Children were classified by atopic status on the basis of skin prick tests. RESULTS: Breast-feeding information was collected prospectively, and lower respiratory tract illnesses in the first 3 years of life were diagnosed by the pediatrician. Being breast-fed was associated with lower rates of recurrent wheeze at age 6 years (3.1% vs 9.7%, P < .01) for nonatopic children; this relationship was not significant for atopic children. The relationship of breast-feeding with recurrent wheeze was apparent among nonatopic children both with and without a wheezing lower respiratory tract illness in the first 6 months of life. When potential confounders, including early wheezing lower respiratory tract illness, were included in a multivariate model, nonatopic children who had not been breast-fed had three times the odds of wheezing recurrently (odds ratio, 3.03; confidence interval, 1.06 to 8.69). Eleven percent of recurrent wheeze among nonatopic children could be attributed to not breast feeding. CONCLUSIONS: Recurrent wheeze at age 6 years is less common among nonatopic children who were breast-fed as infants. This effect is independent of whether the child wheezed with a lower respiratory tract illness in the first 6 months of life. PMID- 7795767 TI - California pediatricians' knowledge of and response to recommendations for universal infant hepatitis B immunization. AB - OBJECTIVE: To assess California pediatricians' level of agreement with and implementation of universal infant hepatitis B immunization. RESEARCH DESIGN: Mailed questionnaire in the summer and fall of 1993 to a random sample of 1030 California pediatricians to determine whether they universally immunize infants with hepatitis B vaccine. The response rate was 71%. RESULTS: More than 81% said they universally immunize infants against hepatitis B infection; however, 18.3% stated that they do not. Pediatricians were more likely to immunize infants universally against hepatitis B if they (1) agreed with the recommendations (90% vs 54%, P < .01), (2) practiced in a health maintenance organization setting vs private group practice (92% vs 79%, P < .05), or (3) practiced in settings with predominantly low-income patients (89% vs 78%, P = .01). Pediatricians who universally immunize infants against hepatitis B virus were in practice an average of 1.7 years longer than those who do not (13.3 years vs 11.6 years, P = .01). In multivariate analyses, the most powerful predictor of universal immunization was agreement with the recommendations. Among those who disagreed with the recommendations, the most common reasons for disagreement included the following: (1) the long-term efficacy of hepatitis B vaccine is not proved--54%; (2) an additional immunization would make the visits too costly--53%; and (3) three shots would be too much at one visit--53%. CONCLUSIONS: A majority (81.6%) of our sample of California pediatricians universally immunize infants against hepatitis B; however, a significant minority (18.4%) do not agree with the recommendations and do not plan to implement them. Many of their objections are being addressed through combination vaccine development and ongoing research; however, alternative policies and additional research should also be considered. PMID- 7795766 TI - Postoperative neurologic complications after open heart surgery on young infants. AB - OBJECTIVE: To ascertain the relation between postoperative neurologic complications and variables occurring before, during, and after hypothermic cardiopulmonary bypass surgery to correct congenital heart disease in young infants. DESIGN: Prospective analysis of mortality and neurologic morbidity before hospital discharge; systematic comparison with patient characteristics, metabolic status, surgery variables; and preoperative neurologic findings of the patients. SETTING: Intensive care unit in tertiary care center. PATIENTS: Consecutive sample of 91 full-term infants who underwent 100 operations between January 1989 through December 1992. Nine infants had more than one operation during the study period. MAIN OUTCOME MEASURES: Levels of alertness, tone, focal signs, dyskinesia, pyramidal signs, seizures, and death. RESULTS: Reduced level of alertness at discharge from the hospital in 19% of patients; seizures in 15% (70% focal); severe hypotonia in 11% before surgery, and in 7% at discharge from hospital; generalized pyramidal findings in six (7%); asymmetry of tone in 5%; and chorea that did not persist in 11%. Results of cranial ultrasound tests were abnormal in 20% of patients. Of these those with abnormal cranial ultrasound examinations 55% were abnormal before surgery. Overall mortality was 18%. Of the patients who died, 59% had interrupted aortic arch or hypoplastic left heart syndrome. Mortality for patients with these lesions was 40%. Alertness (P = .005), chorea (P = .03), and hypotonia (P = .02) were associated with duration of deep hypothermia longer than 60 minutes. No association was found among other outcomes and study variables, except the relation between severe left-sided heart lesions and mortality. CONCLUSIONS: Mortality and neurologic morbidity after open heart surgery on young infants may be due to several factors, including type of lesion, preexisting brain abnormalities, duration of deep hypothermia, and strokes. PMID- 7795768 TI - Mumps outbreak in a highly vaccinated school population. Evidence for large-scale vaccination failure. AB - OBJECTIVES: To describe an outbreak and to identify risk factors for mumps occurring in a highly vaccinated high school population. (Note: Highly vaccinated means a population in which more than 95% have been vaccinated.) DESIGN AND PARTICIPANTS: Survey and cohort study of 307 (97%) of 318 students. OUTCOME MEASURES: Mumps was defined as an illness with 2 or more days of parotid swelling. Serologic confirmation of infection was obtained in eight cases, seven of which were evaluated for presence of IgM antibody using immunofluorescent antibodies. Vaccination records were verified for 297 (97%) students. RESULTS: Between October 3 and November 23, 1990, clinical mumps developed in 54 students (attack rate, 18%), 53 of whom had been vaccinated. Most cases (40 [77%] of 52) occurred 12 to 20 days after a school-wide pep rally. Immunofluorescent antibody testing of all seven specimens demonstrated IgM antibody to mumps. Risk factors for clinical mumps identified in multivariate analyses included female gender (odds ratio, 3.0; 95% confidence interval, 1.6 to 5.7) and source of vaccination other than the local public health clinic (students vaccinated by private providers [odds ratio, 3.0; 95% confidence interval, 1.3 to 5.2] or in other districts [odds ratio, 2.4; 95% confidence interval, 1.1 to 5.3]). CONCLUSIONS: The overall attack rate is the highest reported to date (and to our knowledge) for a population demonstrating virtually complete mumps vaccine coverage. Even verified documentation of vaccination may not be an accurate indicator of an individual's protection against mumps. Vaccination failure may play an important role in contemporary mumps outbreaks. We found no evidence to indicate that waning immunity (secondary vaccine failure) contributed significantly to this outbreak. A second dose of mumps vaccine, as recommended using measles-mumps rubella vaccine, could potentially prevent similar outbreaks in secondary school populations in the future. PMID- 7795769 TI - Results of 12 nationwide epidemiological incidence surveys of Kawasaki disease in Japan. AB - OBJECTIVE: To describe the long-term trend of incidence and other epidemiological pictures of Kawasaki disease in Japan, by using the results of 12 nationwide epidemiological surveys on Kawasaki disease that have been conducted throughout Japan (ie, surveys that have encompassed the pediatric departments of hospitals with more than 100 beds) every 2 years since 1970. RESULTS: At the end of December 1992, the total number of patients with this disease was 116,848 (males, 67,815; females, 49,033; male-female ratio, 1.38). The number of cases increased year by year, with three outbreaks in 1979, 1982, and 1986. There have been no cyclical changes since 1986. The incidence was higher in males and in those children who were 1 year of age or younger. The fatality rate decreased from 1% in 1974 to 0.04% in 1992. CONCLUSIONS: The patterns of descriptive epidemiology, such as seasonality and cyclical changes in incidence, supported the theory of an infectious agent as the causal agent. However, the incidence data since 1986 provide less support for an infectious theory. PMID- 7795770 TI - Inappropriate infant bottle feeding. Status of the Healthy People 2000 objective. AB - OBJECTIVE: To provide information on baby bottle use in the United States because of the important consequences, including early childhood caries, associated with inappropriate feeding practices. METHODS: Data from the child supplement to the 1991 National Health Interview Survey were examined. Information was collected on one randomly selected child from each family with children in the survey; data were weighted to represent the corresponding US population. Questions about the "ever use" and "still use" of baby bottles, and selected sociodemographic and health behavior variables were assessed. RESULTS: About 95% of children 6 months to 5 years old have ever used a baby bottle. Nearly one fifth of the children in this age range were put to bed with a bottle that had contents other than water. More than 8% of children 2 to 5 years old still use the bottle. Bivariate and multivariate analyses showed differences in bottle practices by education level of the adult caretaker, dental visits, Hispanic background, race, and geographic region. CONCLUSION: The high prevalence of feeding with a baby bottle requires pediatricians and other health care professionals to help reduce the risks to health. PMID- 7795771 TI - Immunization status and birth order. AB - OBJECTIVE: To determine whether an association exists between immunization status and birth order. DESIGN: Medical record review of immunization dates for matched siblings. SETTING: Pediatric clinic at a university medical center. SUBJECTS: A total of 892 children (446 sibling pairs of firstborn and secondborn children) born between 1983 and 1991 who received regular pediatric care at the clinic. OUTCOME MEASURES: Median ages at which firstborn children and their secondborn siblings had been immunized with the initial four doses of diphtheria and tetanus toxoids and pertussis vaccine (DTP1, DTP2, DTP3, and DPT4) and the initial dose of measles-mumps-rubella vaccine; point prevalences of firstborn and secondborn children up-to-date with all immunizations at each month of life to 2 years of age. RESULTS: Between 5 and 12 months of life, the percentage of secondborn children who were fully immunized was significantly lower than the percentage of fully immunized firstborn children (P values ranging from < .0001 to < .05). Firstborn children were much more likely than their secondborn siblings to have been immunized on time with DTP2 (z = 3.80, P = .0001) and DTP3 (z = 3.31, P = .0009). Overall, DTP2 immunizations were given at median ages 10 days later, and DTP3 immunizations, 20 days later to secondborn children than to their firstborn siblings. In addition, late immunization of a firstborn child was found to increase the risk that a secondborn sibling would also be immunized late. CONCLUSIONS: Secondborn children are likely to be immunized later than firstborn children. Secondborn children with an older sibling who was immunized late are at particular risk for delayed immunizations. PMID- 7795772 TI - Breast-feeding in a low-income population. Program to increase incidence and duration. AB - OBJECTIVE: To evaluate the efficacy of an intervention program to increase breast feeding in a low-income, inner-city population. DESIGN: A randomized, nonblinded clinical control trial. Patients were followed up through pregnancy, delivery, and the first year of the infant's life or until the time of weaning from the breast, whichever came first. SETTING: The ambulatory care center for prenatal and pediatric care and the inpatient maternity unit of a primary care center that serves a low-income, inner-city population. PATIENTS: There were a total of 108 patients: 51 were randomized to the intervention group that received prenatal and postnatal lactation instruction from a lactation consultant, and 57 were randomized to the control group that received the standard of care at the institution. Patients in the control group were not seen by the lactation consultant. The two groups were similar demographically. INTERVENTION: This program consisted of individual prenatal lactation consultation, daily rounds by the lactation consultant on the postpartum unit, and outpatient follow-up at 48 hours after discharge, at the time that the infant was 1 week of age, and at all future health supervision visits for infants up to 1 year of age. MAIN OUTCOME MEASURES: The incidence and duration of breast-feeding. RESULTS: There was a markedly higher incidence of breast-feeding in the intervention group, as compared with that of the control group (61% vs 32%, respectively; P = .002). The duration of breast-feeding was also significantly longer in the intervention group (P = .005). CONCLUSIONS: This lactation program increased the incidence and duration of breast-feeding in our low-income cohort. We suggest that similar efforts that are applied to analogous populations may increase the incidence and duration of breast-feeding in low-income populations in the United States. PMID- 7795773 TI - Predictors of sunscreen use in childhood. AB - OBJECTIVE: To identify risk factors predictive of sunscreen use in children. DESIGN: Cross-sectional review of convenience sample. SETTING: Emergency department of a regional referral pediatric hospital. SUBJECTS: Nine hundred twenty-five parents of children presenting to the emergency department in August 1993. MAIN OUTCOME MEASURES: Parental risk factors assessed were use of sunscreen, tanning behaviors, previous blistering sunburn, knowledge of cancer risk related to sunburn and sun protection factor definition, education level, and other health-promoting behaviors. The parents were asked about perceived risk for their child's being sunburned in the next month or development of skin cancer in their lifetime, as well as an estimation of safe sun exposure time for their child. Child risk factors included a history of previous painful sunburn and parental assessment of their child's skin type based on susceptibility to sunburn. RESULTS: Eighty-four percent of parents reported that their children had used sunscreen at least once in the previous 2 months. The use of sunscreen in children younger than 1 year was 54%, from 1 to 12 years of age was 91%, and older than 12 years was 68%. Factors associated with increased likelihood of sunscreen use were age of 1 to 12 years, parental use of sunscreen, estimation of safe sun exposure of less than 30 minutes, description of child skin type as burns "sometimes," "easily," or "always," and correct definition of sun protection factor. Application of a multivariate model yielded a sensitivity of 96%, specificity of 36%, and positive predictive value of sunscreen use of 89%. CONCLUSIONS: Sunscreen use in parents is predictive of use in their children and relates more to experience with sunburn than with concerns about future skin cancer risk. PMID- 7795774 TI - Comparison of 1% and 2.5% selenium sulfide in the treatment of tinea capitis. AB - OBJECTIVE: To determine whether an over-the-counter shampoo containing 1% selenium sulfide would have sporicidal activity equal to that of a 2.5% selenium sulfide prescription lotion in the adjunctive treatment of tinea capitis infection. DESIGN: Prospective randomized nonblinded clinical trial. SETTING: Outpatient clinics and emergency department of a children's hospital. PATIENTS: Fifty-four patients between the ages of 1 and 15 years with culture-proved tinea capitis infection caused by Trichophyton tonsurans enrolled during a 14-month period. METHODS: Patients were randomized to receive 2.5% selenium sulfide lotion, 1% selenium sulfide shampoo, or a bland, nonmedicated shampoo with which they were instructed to shampoo twice weekly. All received 15 mg/kg per day of griseofulvin. Dermatophyte cultures of the affected area of each patient's scalp were obtained on enrollment and every 2 weeks until a negative culture was obtained from a previously infected area. RESULTS: Survival data analysis demonstrated that both the 2.5% selenium sulfide and 1% selenium sulfide preparations were superior to the nonmedicated control shampoo in terms of the time required to eliminate shedding of viable spores. When compared with each other, there was no difference between the 2.5% selenium sulfide and 1% selenium sulfide preparations in time required to produce a negative culture. CONCLUSION: Commercially available 1% selenium sulfide shampoo is an equally effective yet less expensive alternative sporicidal therapy in the adjunctive treatment of tinea capitis infection. PMID- 7795775 TI - When patients and pediatricians say good-bye in a pediatric resident continuity clinic. AB - Pediatric residency programs require a 3-year continuity clinic experience for residents. To our knowledge, no authors have examined the impact of termination at the end of the residency among the child, parent, and pediatrician. This article discusses an exploration that evolved in response to the questions that third-year pediatric residents asked concerning how to say good-bye to their primary care patients in the context of their continuity clinic. The first panel addressed parental and patient issues, and the second addressed the impact on the pediatrician. The parents on the panel stated that it was important that they be notified in advance of their pediatrician's departure, that they believed they had played an important role in the resident's education, and that they wanted a voice in the selection of their child's future pediatrician. The pediatricians on the panel all felt sadness, relief, and guilt as a result of the termination, but guilt that the family would feel abandoned was the strongest emotion. Few pediatricians on the panel acknowledged the impact of the relationship on themselves and the importance of including the parents in the decision to choose the child's future pediatrician. The issue of termination needs more deliberate attention in pediatric training programs. A structured system for teaching residents to manage the termination process is proposed. PMID- 7795776 TI - Radiological case of the month. Granulocytic sarcoma. PMID- 7795777 TI - Picture of the month. Loose anagen syndrome. PMID- 7795778 TI - Thrombocytopenia in neonates with trisomy 21. PMID- 7795779 TI - High-performance liquid chromatographic analysis with electrochemical detection of biogenic amines using microbore columns. AB - High-performance liquid chromatography with electrochemical detection (HPLC-ED) is a popular method for measuring biogenic amines, owing to its simplicity, versatility, sensitivity, and specificity. Recent developments in microbore column HPLC-ED have been facilitated by miniaturization of solvent delivery, column packing, sample injection and micro-flow cell construction. The aim of this paper is to present an overview of recent developments in microbore column HPLC-ED, in terms of advantages and limitations. This paper covers the recent advancements and important factors of HPLC-ED analysis of biogenic amines using microbore columns. Particular emphasis is placed on applying this technique to microdialysis, for which great sensitivity is required. Its potential in future biomedical applications is also discussed. PMID- 7795780 TI - Quantitative determination of diol metabolites of CS-670, a new antiinflammatory agent, by capillary column gas chromatography-mass spectrometry. AB - CS-670(I), being developed as a non-steroidal anti-inflammatory agent, is a racemic prodrug. It has been found to be readily metabolized to active metabolites: trans and unsaturated mono-ols (trans-OH, unsaturated-OH). We report here a method for the quantitative determination of the eight diol stereoisomers excreted in urine after administration I. The diols were well separated and quantitated using capillary column GC-MS after a rather simple derivatization with diazomethane-trifluoroacetic anhydride. Sex differences in rats and species differences between rats and mice were observed in the metabolism of I: the trans diols originating from trans-OH were predominantly excreted in male and female rat urine but the excretion rate was greater in the male rats; the cis-diols originating from cis mono-ol (cis-OH) were the major urinary metabolites in mice. The hydroxy groups were mainly introduced at the respective equatorial hydrogen atoms at the 4'-carbon of trans-OH and the 5'-carbon of cis-OH. The 4'- and 5' hydroxy groups in the diols were in the cis conformation with respect to the original 2'-hydroxy group. As approximately 9% of the trans-diols were excreted in urine after administration of cis-OH to rats, the chiral inversion from cis-OH to trans-OH was suggested to occur through the saturated ketone intermediate. PMID- 7795781 TI - Determination of berberine in plasma, urine and bile by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of berberine in plasma, urine and bile samples is described. Plasma samples were pretreated by protein precipitation with acetonitrile and urine and bile samples were pretreated by organic solvent extraction using 5% 2-propanol in methylene chloride. Berberine was determined in all samples using an octyl reversed-phase column with a mobile phase of 60-63% acetonitrile in 0.1% phosphoric acid (pH 6.0) and with UV detection at 267 nm. The detection limits for berberine in plasma, urine and bile were 18.1 ng/ml, 2.3 ng/ml and 90.4 ng/ml, respectively. The recoveries of berberine by simple deproteinization of plasma and by solvent extraction of urine were 78.3 and 82.9%, respectively. The intra-day and inter day accuracy and precision for plasma reported as coefficients of variation and relative errors were both less then 6%. The applicability of the assay to pharmacokinetic and bioavailability studies was demonstrated by the determination of berberine in plasma, urine and bile after intravenous and intramuscular administration to rabbits at a dose of 2 mg/kg. PMID- 7795782 TI - High-performance liquid chromatographic determination of (S)- and (R)-propranolol in human plasma and urine with a chiral beta-cyclodextrin bonded phase. AB - The determination of propranolol enantiomers in microsamples of human plasma and urine by HPLC using a chiral stationary phase is described. After extraction from 200 microliters of plasma or urine with racemic alprenolol as internal standard (I.S.), the enantiomers are separated on a beta-cyclodextrin column with a polar organic mobile phase and determined by fluorescence detection. The retention times of I.S. and propranolol enantiomers are about 12-13 min and 16-18 min, respectively. Peak resolutions are 1.4 for I.S. and 2.2 for propranolol. The use of alprenolol as I.S. improves significantly the coefficients of variation (C.V.: 0.6-4.2%). Sensitivity is approximately 1.5 ng/ml per propranolol enantiomer. The assay is applied to pharmacokinetic studies of racemic propranolol in human biological fluids. The (S)-propranolol levels are always higher than the (R) antipode concentrations in plasma and urine. PMID- 7795783 TI - Enantioselective determination of thiamylal in human serum by high-performance liquid chromatography. AB - Thiamylal, a widely used anesthetic drug, has two enantiomers. We developed a novel and simple method for measuring thiamylal enantiomers in human serum using reversed-phase high-performance liquid chromatography. R(+)- and S(-)-Thiamylal were separated using a chiral mobile phase containing beta-cyclodextrin, and detected at the range of 50 ng/ml-25 micrograms/ml in serum. The relative standard deviations of R(+)- and S(-)-thiamylal were 3.4-8.7% and 2.8-8.7% for the intra-day assay, and 2.8-12.0% and 2.8-13.0% for the inter-day assay. This method may be applied to enantioselective pharmacokinetic studies of thiamylal. PMID- 7795784 TI - Achiral and chiral analysis of camazepam and metabolites by packed-column supercritical fluid chromatography. AB - Supercritical fluid chromatography, using carbon dioxide as the mobile phase and ethanol as a modifier, has been applied to the analysis of products formed in rat liver microsomal metabolism of racemic camazepam, a hypnotic/anxiolytic drug in clinical use. An achiral (amino) column and a chiral (Chiralcel OD-H) column were used. The results suggest that achiral and chiral packed-column supercritical fluid chromatography gives a shorter analysis time and higher selectivity and efficiency than achiral and chiral stationary-phase high-performance liquid chromatography in the analysis of camazepam and its derivatives. PMID- 7795785 TI - Determination of metyrapone and the enantiomers of its chiral metabolite metyrapol in human plasma and urine using coupled achiral-chiral liquid chromatography. AB - A coupled achiral-chiral liquid chromatographic assay has been developed to determine the concentrations of metyrapone and the enantiomers of its chiral metabolite metyrapol in plasma and urine. The chromatographic system consisted of a silica precolumn (75 x 4.6 mm I.D.) coupled in-line to a 250 x 4.6 mm I.D. column containing cellulose tris(4-methylbenzoate) coated on silica gel (Chiralcel OJ-CSP). When plasma samples were analyzed, the mobile phase was hexane-ethanol (92:8, v/v) modified with 0.1% diethylamine and when urine samples were analyzed the mobile phase was hexane-ethanol (94:6, v/v) modified with 0.2% diethylamine. Under these chromatographic conditions the chromatographic retentions [expressed as capacity factors (k')] for metyrapone were k' = 2.35 (plasma) and 2.52 (urine); for (-)-metyrapol k' = 4.22 (plasma) and 4.62 (urine); for (+)-metyrapone k' = 5.16 (plasma) and 5.86 (urine); enantioselectivities (alpha) were 1.09 (plasma) and 1.13 (urine). The assay has been validated for use in metabolic studies. The analyses of plasma and urine samples from one subject following oral administration of 750 mg of metyrapone indicated that the enzymatic reduction of myterapone by aldo-keto reductase was enantiospecific. PMID- 7795786 TI - Capillary gas chromatographic determination of proteins and biological amino acids as N(O)-tert.-butyldimethylsilyl derivatives. AB - Forty-seven biological amino acids containing all 22 protein amino acids were derivatized to N(O)-tert.-butyldimethylsilyl (tBDMSi) derivatives by a single step reaction with N-methyl-N-(tert.-butyldimethylsilyl)trifluoroacetamide and successfully separated on an HP-1 capillary column. The relative standard deviations of the relative molar responses of most amino acids were < 5%. Cystine seems to be partially converted into cysteine during derivatization. An increase in carrier gas flow-rate towards the end of the analysis by inlet pressure programming with electron pressure control avoided the peak broadening and adsorption of the derivatives with high boiling points on the column and especially increased sensitivity of cystine to 5 pmol. Glutamine was converted almost completely into pyroglutamic acid during prolonged storage of a standard solution prepared in 0.01 M HCl but not during derivatization. These results compared with those for the phenylthiocarbamyl derivatives analysed by HPLC and the analytical results reported in the literature on soybean hydrolysate showed good agreement except for cysteine. The results for the amino acid composition of bovine serum albumin also showed good agreement with results in the literature except for cysteine. In human urine, seventeen free amino acids were detected as tBDMSi derivatives. PMID- 7795787 TI - High-performance liquid chromatographic assay for sodium mercaptoundecahydrododecaborate in rat tissues. AB - Mercaptoundecahydrododecaborate (BSH) is an important agent for the boron neutron capture therapy (BNCT). A sensitive high-performance liquid chromatographic (HPLC) method was developed for measuring BSH concentrations in rat tissues. Various tissue samples containing the drug were homogenized in a 1:1 (g/ml) mixture with phosphate buffered saline. The samples were then deproteinised with 4 volumes of acetonitrile and centrifuged. An aliquot of the supernatant was dried and reconstituted in 200 microliter of Tris-HC1 buffer. The samples were subjected to precolumn derivatization using the thiol reactive monobromobimane (mBB). The drug-mBB adduct was resolved by isocratic elution from a C18 reversed phase column. The optimized mobile phase was methanol-0.02 M phosphate buffer (43:57, v/v) containing 0.01 M tetrabutylammonium dihydrogen phosphate as the ion pairing agent with the final pH adjusted to 7.0. The flow-rate was set at 2.0 ml/min. The adduct was monitored by UV absorption at 373 nm. The analysis was completed in less than 15 min. The detection limit was 0.5 microgram/ml (0.25 microgram of boron). The assay method was linear over a concentration range of 0.5 to 50 micrograms/ml. This assay method could be used to evaluate the BSH concentrations in different tissues in studies on the targeted delivery of BSH. PMID- 7795788 TI - Simultaneous quantitation of methotrexate and its two main metabolites in biological fluids by a novel solid-phase extraction procedure using high performance liquid chromatography. AB - We have developed an assay for the simultaneous determination of methotrexate (MTX) and its main metabolites, 7-hydroxymethotrexate (7-OHMTX) and 2,4-diamino N10-methylpteroic acid (DAMPA) in plasma, urine and saliva meeting the requirement of rapidity for routine use in high-dose MTX therapy and the requirement of sensitivity for its potential use in therapeutic drug monitoring in low-dose MTX therapy. Sample preparation is based on solid-phase extraction using C8 Isolute cartridges. Chromatographic separation was achieved with a reversed-phase column (C18), and quantitation by subsequent exposure to UV light of 254 nm, which converted MTX and its two metabolites by photolytic oxidation to fluorescent products. The recoveries of MTX, 7-OHMTX and DAMPA from plasma at 100 nmol/l were 85.8, 91.1 and 102.3%, respectively. The limits of detection for MTX, 7-OHMTX and DAMPA in plasma and saliva were 0.1 nmol/l. In urine the limit of detection was 10 nmol/l for all compounds. The limits of quantitation in plasma and saliva were 0.5 nmol/l for all compounds. PMID- 7795789 TI - Validated assays for the determination of gemcitabine in human plasma and urine using high-performance liquid chromatography with ultraviolet detection. AB - Procedures are described for the determination of gemcitabine, a new anti-tumor agent, and its uridine metabolite in human plasma and in human urine. The sample preparation for the plasma assay involves precipitation of plasma proteins with isopropanol and ethyl acetate. Following this, the solids are discarded and the supernatant is evaporated to dryness. For the urine assay, the sample is diluted with methanol and evaporated to dryness. For both procedures, the residue is reconstituted in mobile phase prior to injection into a normal-phase (amino column) liquid chromatographic system followed by UV detection at 272 nm. The limits of quantitation for both compounds are 50 ng/ml in plasma and 20 micrograms/ml in urine. The procedures were used to provide pharmacokinetic data for both compounds in man following the intravenous administration of a 1000 mg/m2 dose of gemcitabine. PMID- 7795791 TI - Sensitive high-performance liquid chromatographic method for a dopamine receptor agonist, CI-1007, and its metabolite PD 147693 in monkey plasma. AB - A sensitive gradient high-performance liquid chromatographic (HPLC) method for the simultaneous quantitation of a dopamine autoreceptor agonist CI-1007 (I) and its metabolite PD 147693 (II) is described. Monkey plasma samples were purified by liquid-liquid extraction using hexane. Liquid chromatographic separation was achieved on two C18 analytical columns (installed in series) using gradient elution. Column effluent was monitored using a fluorescence detector programmed to change wavelengths at specified times. Minimum quantitation limits of I and II were 3.0 and 5.0 ng/ml, respectively, for a plasma sample volume of 0.100 ml. Linearity was demonstrated up to 300 ng/ml. The assay has been applied to the analysis of I and II in plasma from monkeys following intravenous and oral doses of I. PMID- 7795790 TI - Highly sensitive high-performance liquid chromatographic assay for 1-beta-D arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate). AB - An ion-pair HPLC method for the determination of 1-beta-D arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate I) was developed, using a phenyl-bonded column under reversed-phase conditions with a mobile phase of acetonitrile-buffered water (pH 6.8) (50:50) for isocratic elution. A reproducible sample clean-up was achieved by solid-phase extraction. In order to reach the low limit of detection of 2 ng/ml, an enrichment switching system was used. The present validation leads to a limit of quantification of 5 ng/ml with a coefficient of variation (C.V.) of 10%. The total time of measurement was shortened by a back-flush procedure to restore the conditions after each run. UV detection at 275 nm was applied. The recoveries for plasma samples ranged from 56.4 to 64.1%, regardless of drug concentrations. The intra assay C.V. was about 4% (40 measurements at four different concentrations). The inter-assay recovery (ten measurements over ten days) at a plasma concentration of 50 ng/ml was 57% with a C.V. of 8.25%. Based on this HPLC method, the pharmacokinetics of I were measured during a clinical phase I/II study. PMID- 7795792 TI - Determination of theophylline and its metabolites in rat liver microsomes and human urine by capillary electrophoresis. AB - A capillary electrophoretic (CE) method has been developed for the determination of theophylline and all of its identified and potential metabolites. The method is rapid, resolves all metabolites to baseline, and requires extraction of only some biological fluids. It has been applied to the analysis of theophylline metabolism by hepatic microsomes from rats treated with a variety of inducing agents for different forms of P450 enzymes which metabolize theophylline, and to human urine spiked with theophylline and its metabolites, and concentrated by solid-phase extraction. PMID- 7795793 TI - High-performance liquid chromatographic determination of primary aromatic amines in urine after derivatization to an azo dye with 2-aminoanthracene. AB - A sensitive HPLC method for the determination of primary aromatic amines (anilino compounds) is described. Samples were prepared by derivatization of the substrate to an azo dye with 2-aminoanthracene (2-AA). 2-AA was found to react with the diazonium salts prepared from substituted anilines such as 4-halo, -sulfonyl, carboxyl, -nitro or -acetyl derivatives, but not 4-hydroxy or -alkyl derivatives. In this work, three model compounds [sulfanilamide, 4-aminobenzoyl-beta-alanine and 4-aminobenzoic acid (PABA)] were used to test the linearity and accuracy of the method. Chromatographic separation was carried out using a reversed-phase column (ODS) and ultraviolet detection at 279 nm. Good linearity for the three compounds was found within the range 50-2000 ng/ml. The intra-day coefficient of variation for the three compounds (at 100, 500, 1000 ng/ml) was below 10%. Using this method, the urinary excretion of PABA and its metabolites was studied after oral administration of PABA to rats. PMID- 7795794 TI - Determination of thiopurine nucleotides in human lung tissue by high-performance liquid chromatography. AB - A method for the analysis of thiopurine nucleotides in human transbronchial lung biopsy was developed. The sample treatment procedure is based on perchloric acid homogenisation and deproteinisation with dithiothreitol and hydrolysis of thiopurine nucleotides into their free bases by heating of the acid extract. Then, the free bases were analyzed in the gradient elution mode on a Hypersil ODS, 3-microns column using dihydrogenphosphate buffer-methanol as eluent. Mean analytical recoveries for 6-thioguanosine monophosphate and 6-thioinosinic acid from lung tissue were 97.0 +/- 2.0 and 98.0 +/- 1.8% at a concentration of 3.0 nmol/ml and the minimum detectable amounts were 3.5 and 2 pmol, respectively. The procedure described is simple and represents a suitable method for the investigation of thiopurine nucleotides in tissues. PMID- 7795796 TI - Determination of chlorhexidine in saliva using high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic method for the determination of chlorhexidine in saliva is reported. The method developed includes a simple and short sample preparation with a one-step extraction procedure and a short total chromatographic run time of 5 min. In a preliminary pharmacokinetic study with a healthy volunteer the chlorhexidine concentration found in saliva after 12 h was 0.8 microgram/ml. PMID- 7795795 TI - Simultaneous determination of midazolam and flumazenil concentrations in human plasma by gas chromatography. AB - A gas chromatographic method for the simultaneous determination of midazolam and flumazenil concentrations in human plasma has been developed, using clinazolam as the internal standard. A mixture of chloroform and ethyl acetate (80:20) was used to extract the two compounds. A 2-microliters volume of the reconstituted sample was injected using a 1:20 split injection mode. Intra-day coefficients of variation ranged from 2 to 6.9%. The assay was linear over the range 3-1000 ng/ml. This assay was subsequently used to analyze samples from a human pharmacokinetic study. PMID- 7795797 TI - Determination of a novel cognitive enhancer, X9121, and its mono N-oxide metabolite, XG696, in dog plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection. AB - A selective and sensitive high-performance liquid chromatographic assay for a novel cognitive enhancer, X9121 (I), and its mono N-oxide metabolite, XG696 (II), in dog plasma has been developed. Compounds I, II and internal standard (I.S.) were first extracted from dog plasma using a solid-phase Bond Elut Certify I 10 ml LRC reservoir extraction cartridge. Chromatographic separation of I, II and I.S. was conducted on a reversed-phase Zorbax Stable Bond cyano column. Ammonium acetate buffer (0.05 M, pH 6)-acetonitrile-triethylamine (75:25:0.1, v/v) was used as the mobile phase. Detection of all three compounds was by UV light absorbance at 313 nm. Using 0.5 ml of dog plasma for extraction, the minimum quantifiable limit was 10 ng/ml and the assay was linear from 10 to 5400 ng/ml. The coefficients of variation for intra-day precision ranged from 2.2 to 8.5% for I and from 2.5 to 9.8% for II. The coefficients of variation for the inter-day precision for these two compounds ranged from 2.6 to 9.0% and from 3.6 to 16.2%, respectively. The absolute percent differences for the accuracy results were within 11.0% of the spiked concentrations. Compounds I and II were stable in frozen plasma at -20 degrees C for at least 67 days. PMID- 7795798 TI - Determination of oxalate in urine and plasma using reversed-phase ion-pair high performance liquid chromatography with tris(2,2'-bipyridyl)ruthenium(II) electrogenerated chemiluminescence detection. AB - Oxalate is quantitated in both urine and plasma samples using reversed-phase ion pair high-performance liquid chromatography (HPLC) with tris(2,2' bipyridyl)ruthenium(II) [Ru(bpy)2+(3)]-electrogenerated chemiluminescent (ECL) detection. Underivatized oxalate was separated on a reversed-phase column (Zorbax ODS) using a mobile phase of 10% methanol in 100 mM phosphate buffer at pH 7.0. The eluted compounds were combined with a stream of 2 mM Ru(bpy)2+(3) at a mixing tee before the ECL flow-cell. In the flow-cell, Ru(bpy)2+(3) is oxidized to Ru(bpy)3+(3) at a platinum electrode, and reacts with oxalate to produce chemiluminescence (CL). Urine samples were filtered and diluted prior to injection. Plasma samples were deproteinized before injection. A 25-microliters aliquot of sample was injected for analysis. Possible interferants, including amino acids and indole-based compounds, present in biological samples were investigated. Without the separation, amino acids interfere by increasing the total observed CL intensity; this is expected because they give rise to CL emission on their own in reaction with Ru(bpy)3+(3). Indole compounds exhibit a unique interference by decreasing the CL signal when present with oxalate. Indoles inhibit their own CL emission at high concentrations. By use of the indicated HPLC separation, oxalate was adequately separated from both types of interferants, which thus had no effect on the oxalate signal. Urine samples were assayed by both HPLC and enzymatic tests, the two techniques giving similar results, differing only by 1%. Detection limits were determined to be below 1 microM (1 nmol/ml) or 25 pmol injected. The working curve for oxalate was linear throughout the entire clinical range in both urine and plasma. PMID- 7795799 TI - Automatic determination of hydroperoxides of phosphatidylcholine and phosphatidylethanolamine in human plasma. AB - An automatic method for the determination of hydroperoxides of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is reported. Sample plasma was deproteinized with a fourfold volume of methanol. After centrifugation, the supernatant was injected directly into an HPLC system without further treatment. The hydroperoxides of PC and PE were concentrated and washed on an ODS column followed by introduction into two analytical columns, a silica gel and an aminopropylsilica gel column, which were connected in series, by column switching. After the separation, they were detected by postcolumn detection with diphenyl-1-pyrenylphosphine. The compounds were determined at picomole levels within 30 min with good reproducibilities. By using only a silica gel column as an analytical column, PC hydroperoxides were determined within 20 min, and samples could be injected into it at 15-min intervals. Those methods made it possible to inject a sample of up to 2 ml at one time and up to 8 ml by repeated injections and to determine phospholipid hydroperoxides in human plasma at picomole levels. PMID- 7795800 TI - Assay of urinary free and conjugated 3-methoxy-4-hydroxyphenylethyleneglycol by high-performance liquid chromatography with amperometric detection. AB - The aim of this study was to develop an analytical method for free and conjugated 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in urine. After hydrolysis of the conjugated forms, the urinary MHPG was purified by solid-phase extraction on anion exchanger and eluted with a water-methanol (1:1, v/v) mixture. After addition of ethyl acetate to the eluate and back-extraction into acetic acid, the aqueous phase was separated on a C18 column by HPLC and detected amperometrically. The results obtained from forty healthy human subjects were compared with the literature values. The precision and accuracy of the assay were studied using 4-methoxy-3-hydroxyphenylethyleneglycol (iso-MHPG) as internal standard. PMID- 7795802 TI - Evaluation of 2-iminoimidazolidin-4-one and thymine as respective internal standards for normal-phase and reversed-phase high-performance liquid chromatographic determination of creatinine in human serum. AB - We evaluated two internal standards for HPLC determination of creatinine in human serum after ultrafiltration: 2-iminoimidazolidin-4-one for normal-phase HPLC on aluminium oxide, and thymine for C18 reversed-phase HPLC. Detection of 2 iminoimidazolidin-4-one was done at the same wavelength as that used for creatinine, i.e. 240 nm. For thymine, the wavelength was switched to 280 nm. The suitability of the selected compounds to serve as an internal standard in the described measurement procedures, including ultrafiltration of serum, was evaluated from the precision and accuracy obtained. The method based on normal phase HPLC with 2-iminoimidazolidin-4-one showed an imprecision expressed as R.S.D. ranging from 0.8 to 3.4% (mean: 2.1%) and an inaccuracy, calculated from the deviations from target values determined by isotope-dilution gas chromatography-mass spectrometry, ranging from -1.3 to +1.8% (mean: +0.4%). For the reversed-phase HPLC procedure with thymine, the imprecision ranged from 0.3 to 1.3% (mean: 1.0%) and the inaccuracy from +0.1 to +3.9% (mean: +1.7%). The occasional observation of interferences with 2-iminoimidazolidin-4-one limited the application of the normal-phase method to a certain extent. PMID- 7795801 TI - Isolation of individual amino acids from various microbiological sources using reversed-phase high-performance liquid chromatography. AB - A new method for the preparative isolation of individual amino acids on a milligram scale based on reversed-phase high-performance liquid chromatography (RP-HPLC) after pre-column derivatization with carbobenzoxychloride (Z-Cl) has been developed. The chromatographic procedure was tested by the investigation of jack bean urease hydrolysate. The method has been applied to the preparative separation of Z-amino acids (from 10 up to 16) obtained from protein hydrolysates of various sources (green microalgae, blue-green algae, halophilic and methylotrophic microorganisms) and was proved to be reliable by the separation of deuterated amino acids (enrichment 97-99%) from Methylobacillus flagellatum (due to the bioconversion of CD3OD and D2O). Independent of the biological source of the protein, the amino acids were isolated with high recovery (from 68% up to 89%) and chromatographic purity (from 96% up to 99%). The method was also applied for the isolation of phenylalanine and leucine excreted by amino-acid overproducing microorganisms. PMID- 7795803 TI - High-performance liquid chromatographic determination of nicotinic acid and nicotinamide in biological samples applying post-column derivatization resulting in bathmochrome absorption shifts. AB - An ion-pair reversed-phase high-performance liquid chromatographic procedure for the rapid separation and sensitive quantitation of nicotinic acid (NA) and nicotinamide (NAM) in biological samples was developed. The vitamers were separated within 10 min on an octadecylsilica column applying a linear gradient of tetrabutylammonium phosphate and methanol. NA and NAM were converted to highly absorbing derivatives by a modified Konig's reaction using a double post-column derivatization arrangement consisting of two pumps and two knitted tubular reactors. The proposed method is highly sensitive and specific and applicable to biological materials as was shown by the analysis of rat intestinal tissue. PMID- 7795804 TI - Analysis of dipalmitoyl phosphatidylcholine in amniotic fluid by enzymatic hydrolysis and high-performance thin-layer chromatography reflectance spectrodensitometry. AB - A novel test for the determination of dipalmitoyl phosphatidylcholine (DPPC) in amniotic fluid (AF) as free dipalmitoylglycerol (DPG), is described. Aliquots of amniotic fluid were hydrolyzed with Bacilus cereus phospholipase C, and the resulting diglycerides analyzed by AgNO3-modified high-performance thin-layer chromatography (HPTLC)-reflectance spectrodensitometry. This HPTLC system provided resolution of DPG and palmitoylpalmitoleoylglycerol (POG) from other 1,2 diglycerides and cholesterol. The turn-around analysis time for triplicate aliquots of amniotic fluid was 40 min. Recoveries ranged between 90 and 98%. In summary, this method provides a quantitative, specific, highly reproducible, and fast turn-around means of analysis of DPPC in amniotic fluid. PMID- 7795805 TI - Determination of vitamin A in dried human blood spots by high-performance capillary electrophoresis with laser-excited fluorescence detection. AB - We have developed a high-performance capillary electrophoresis (HPCE) method to analyze the retinol (vitamin A) concentration as retinol-retinol binding protein (holo-RBP) from microvolumes of serum (5-10 microliters) or one to two drops (approximately 20 microliters) of blood collected and air-dried on blood collection filter paper. A 0.64-cm diameter disk was cut from the dried whole blood specimens and the samples were dissolved in a pretreatment buffer and filtered. Filtrate was injected onto the HPCE column for analysis. The separation was carried out in a 60 cm x 50 microns I.D. fused-silica capillary and the running voltage was 20 kV. A He-Cd laser with a wavelength of 325 nm was used for excitation, and the fluorescence of the holo-RBP complex was monitored at 465 nm by a photodiode. A virtual linear relationship was obtained for the retinol concentrations between HPCE and HPLC for 28 serum samples, 19 dried venous blood samples and 9 capillary dried blood spot samples, indicating that valid measures of serum retinol can be obtained from one to two drops of capillary blood collected on filter paper. The absolute detection limit for retinol by HPCE is below 3 micrograms/l. The method is very useful for vitamin A level screening, especially for children and premature new-born babies. PMID- 7795806 TI - Improved methodology for the detection and quantitation of urinary metabolites of sulphur mustard using gas chromatography-tandem mass spectrometry. AB - Gas chromatography-tandem mass spectrometry (GC-MS-MS) with selected-reaction monitoring was applied to the analysis of urinary metabolites of sulphur mustard, derived from the beta-lyase pathway and from hydrolysis. In the case of beta lyase metabolites, a limit of detection of 0.1 ng/ml was obtained, compared to 2 5 ng/ml using single stage GC-MS with selected-ion monitoring. GC-MS-MS methodology was less useful when applied to the analysis of thiodiglycol bis(pentafluorobenzoate) using negative-ion chemical ionisation although selected reaction chromatograms were cleaner than selected-ion chromatograms. The advantage of using GC-MS-MS was demonstrated by the detection of low levels of beta-lyase metabolites in the urine of casualties who had been exposed to sulphur mustard. PMID- 7795809 TI - Rapid reversed-phase high-performance liquid chromatographic method with double derivatization for the assay of urinary hydroxyproline. AB - An HPLC method with two derivatizations, the first with o-phthaldehyde in order to eliminate interferences due to some primary amino acids eluting with retention times similar to those of hydroxyproline and the second with dabsyl chloride, was developed and evaluated. Calibration graph linearity, influence of agitation and temperature on the preparation of the first derivative and the influence of the detection wavelength were assessed. The analysis time is shorter in comparison with other available methods, and therefore this method is suitable for laboratories that analyse both small and large series of samples. PMID- 7795808 TI - High-performance liquid chromatographic-electrospray mass spectrometric analysis of bile acids in biological fluids. AB - The present work describes the development of HPLC-mass spectrometric systems equipped with an electrospray interface for the quantitative analysis of bile acids. Good separation of free as well as glycine- and taurine-conjugated bile acids was achieved with a C18 reversed-phase column (3 microns particle size, 70 x 4.6 mm I.D.) employing methanol-15 mM ammonium acetate as the mobile phase for both isocratic and gradient mode, at a flow-rate of 0.3 ml/min. This system permits post-column splitting of the eluate for analysis by two different detectors: (1) electrospray-mass spectrometer with a flow-rate of 18 microliters/min; and (2) a complementary evaporative light scattering mass detector. When bile salts were ionized in the electrospray interface operating in the negative-ion mode, only [M-H]- molecular ions were generated; the detection limit was 15 pg injected for all bile acids studied. In the second system, a semi micro pre-column splitting apparatus (Acurate, LC Packings) was utilized: with this device the flow-rate from the HPLC pump was reduced to 1.4 microliters/min and bile acids were separated with a micro-bore C18 column (3 microns particle size, 150 x 0.30 I.D.), using the same mobile phase as above. With this latter system, a head-column enrichment technique can be used: the amount injected can be increased from 60 to 200 nl, permitting an improvement in the detection limit to 5 pg injected. Application of the HPLC-electrospray-mass spectrometric method to bile and serum bile acid analysis is described; preliminary data on the ability of the first system to determine the 13C/12C isotope ratio in 13C-labeled bile acid enriched serum is also critically discussed. PMID- 7795807 TI - Measurement of volatile organic compounds in exhaled breath as collected in evacuated electropolished canisters. AB - A set of three complementary analytical methods were developed specifically for exhaled breath as collected in evacuated stainless steel canisters using gas chromatographic-mass spectrometric detection. The first is a screening method to quantify the carbon dioxide component (generally at 4-5% concentration), the second method measures the very volatile high-level endogenous compounds [e.g. acetone and isoprene at 500-1000 parts per billion by volume (ppbv), methanol, ethanol, dimethylsulfide at 2-10 ppbv], and the third method is designed to measure trace-level environmental contaminants and other endogenous volatile organic compounds (VOCs) (sub-ppbv) in breath. The canister-based sample format allows all three methods to be applied to each individual sample for complete constituent characterization. Application of these methods is shown to be useful in the following ways: analysis of CO2 levels indicates the approximate quantity of alveolar breath collected (as opposed to whole breath) in a sample; levels of major endogenous compounds are shown to be influenced by physical activities and subsequent recovery periods; and environmental exposures to xenobiotic VOCs can be characterized by assessment of post-exposure breath elimination curves. The instrumentation and methodology are described and example chromatograms and quantitative data plots demonstrating the utility of the methods are presented. PMID- 7795810 TI - Characterization of thyroxine-albumin binding using high-performance affinity chromatography. II. Comparison of the binding of thyroxine, triiodothyronines and related compounds at the warfarin and indole sites of human serum albumin. AB - High-performance affinity chromatography was used to examine the binding of thyroid hormones and related compounds at the warfarin and indole sites of human serum albumin (HSA). This was studied by continuously applying L-triiodothyronine (L-T3), L-reverse triiodothyronine (L-rT3) or structural analogs of these compounds to an immobilized HSA column while making injections of site-specific probe molecules (i.e. R-warfarin and L-tryptophan). The results were compared with those obtained previously for L-thyroxine (L-T4). Equilibrium association constants and thermodynamic parameters measured by this approach showed good agreement with previous models reported for L-T4 and L-T3 at their high-affinity sites on HSA. This data confirmed that the phenol groups of L-T4 and L-T3 played a significant role in the binding of these compounds at the indole site. Work performed at the warfarin site and with other solutes (e.g. L-rT3) indicated that additional factors, such as interactions through the thyronine backbone or terminal amine and carboxyl groups of these compounds, could also be involved in the binding of thyroid hormones to HSA. PMID- 7795811 TI - Determination of 2-butoxyethanol and butoxyacetic acid in rat and human blood by gas chromatography-mass spectrometry. AB - A sensitive and selective gas chromatographic-negative-ion chemical ionization mass spectrometric method was developed to simultaneously quantitate 2 butoxyethanol (BE) and butoxyacetic acid (BAA) in rat and human blood at low ng/g levels as pentafluorobenzoyl and pentafluorobenzyl derivatives, respectively. Analysis of 13C-labeled analogs of BE and BAA were found to improve the limits of quantitation to below 2 ng/g. Deuterium-labeled BE and BAA were used as internal standards. Calibration curves were generally linear over three orders of magnitude, with limits of quantitation of 16-18 ng/g for both BE and BAA, and 1.5 and 0.4 ng/g for [13C2]BE and [13C2]BAA, respectively, in human blood. Linearity in rat blood was similar, with limits of quantitation of 22 ng/g for BE and 5 ng/g for BAA. This method was developed for the support of mammalian metabolism studies and human biomonitoring studies involving exposure to BE or [13C2]BE. PMID- 7795812 TI - Determination of Ro 19-6327 (Lazabemide) in human plasma and urine by gas chromatography-negative chemical ionization mass spectrometry. AB - A sensitive and specific analytical method was developed for determination of Ro 19-6327 (Lazabemide) in human plasma and urine samples to provide pharmacokinetic data from clinical trials. The new method employs a simple liquid-liquid extraction to isolate the drug from biological samples. The extract is reacted to form the trifluoroacetyl derivative of Ro 19-6327 and then analyzed by gas chromatography-negative chemical ionization mass spectrometry (GC-NCIMS). The lower limit of quantitation of the assay is 0.05 ng/ml for plasma and 5.0 ng/ml for urine, based on 1-ml aliquots. No interferences from anticoagulants, collection devices, or endogenous constituents of plasma and urine were observed. Recovery (64.3%), inter-assay precision (< 8% R.S.D.), and accuracy (> 85%) of the method were considered acceptable. The assay proved reliable enough to be automated for unattended sample analysis of approximately 50 samples daily. In an additional series of tests, Ro 19-6327 was shown to be stable under conditions that might be encountered during the analysis of samples from clinical trials. PMID- 7795813 TI - Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection. AB - A GC method is described for the determination of xanomeline (LY246708 tartrate) and selected metabolites in rat and monkey plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane. The organic extract was evaporated to dryness and the residue was reconstituted in hexane. The analytes were separated from metabolites and endogenous substances using a DB1701 capillary column. The analytes were detected using nitrogen phosphorus detection (NPD). The limit of quantitation was determined to be 8 ng/ml, and the response was linear from 8 to 800 ng/ml. The method has been successfully applied to rat and monkey samples pursuant to the development of xanomeline as an agent for the symptomatic treatment of Alzheimer's disease. PMID- 7795814 TI - Biosynthesis, characterisation and direct high-performance liquid chromatographic analysis of gemfibrozil 1-O-beta-acylglucuronide. AB - Gemfibrozil 1-O-beta-acylglucuronide was purified from the urine of a volunteer administered gemfibrozil, and an isocratic reversed-phase HPLC method was developed for its direct measurement. Quantitation of gemfibrozil and gemfibrozil 1-O-beta-acylglucuronide was carried out from plasma, following extraction from acidified specimens into ethyl acetate, on a 5-microns CN reversed-phase column with a mobile phase (pH 3.5) containing acetonitrile, tetrabutylammonium sulphate and distilled water, using fluorescence detection at 284 nm excitation and 316 nm emission. Calibration curves were linear for both compounds over a concentration range of 0.1 to 40 mg/l, with intra-assay coefficients of variation < 5% at concentrations of 20.0, 2.0 and 0.2 mg/l, and inter-assay coefficients of variation < 10%. No degradation of gemfibrozil 1-O-beta-acylglucuronide was detected as a result of the analytical procedure. However, a preliminary application of the method indicates that gemfibrozil acylglucuronide is chemically unstable undergoing intra-molecular rearrangement and hydrolysis under physiological conditions. PMID- 7795816 TI - Rapid determination of sulbactam and tazobactam in human serum by high performance liquid chromatography. AB - A simple and rapid HPLC method for the determination of tazobactam and sulbactam, two beta-lactamase inhibitors, in serum for the therapeutic follow-up of patients is described. The effect of the pH of the aqueous mobile phase and column temperature on column efficiency and retention were examined and equations for their dependences were derived. The use of a chromatographic response function showed that methanol-buffer (5:95, v/v) (pH 6.3) as the mobile phase and a 45 degrees C column temperature were optimum values for chromatographic separation. The analytical method was linear from 10 to 200 micrograms/ml. This assay limit range is sufficient for the analysis of human serum. The limit of detection was 10 micrograms/ml for sulbactam and 5 micrograms/ml for tazobactam. The coefficient of variation was less than 5%. The speed at which this assay can be performed makes it especially useful for estimating the levels of these drugs in human serum. PMID- 7795815 TI - Simultaneous determination of lofepramine and desipramine by a high-performance liquid chromatographic method used for therapeutic drug monitoring. AB - A simple reversed-phase HPLC method with ultraviolet detection for the simultaneous measurement of lofepramine and desipramine is described. Only a single alkaline extraction was used, with clomipramine as internal standard. The column used was a Supelco PCN column, and the mobile phase was acetonitrile methanol-0.015 M phosphate buffer (120:35:100, v/v). The average recoveries were 78.8% for desipramine and 103.8% for lofepramine, and limits of quantitation were 25 and 5 nmol/l, respectively. The inter-assay C.V.s for lofepramine and desipramine were 6.0 and 7.6%, respectively. The method is specific and has excellent accuracy, and has been used for therapeutic drug monitoring of patients with depressions treated with lofepramine. Mean steady-state plasma concentrations found for lofepramine and desipramine were 8.5 +/- 6.1 and 123.6 +/- 120.6 nmol/l, respectively. It is concluded that lofepramine in itself has an antidepressive effect. PMID- 7795818 TI - Determination of (+)-catechin in plasma by high-performance liquid chromatography using fluorescence detection. AB - A high-performance liquid chromatographic method, using fluorescence detection, was developed for the determination of (+)-catechin in rabbit plasma. The procedure involved the precipitation of plasma protein using acetonitrile, followed by solid-phase adsorption onto alumina. After washing with water and methanol, the residue was vortex-mixed with perchloric acid solution to release the adsorbed (+)-catechin. Separation was performed on a reversed-phase column using an eluent consisting of phosphoric acid solution with 12% acetonitrile. The excitation and emission wavelengths were set at 280 and 310 nm, respectively. The retention times for (+)-catechin and the internal standard (deoxyhigenamine) were 6.87 and 8.47 min respectively, without any interference. Validations of accuracy and precision were satisfactory in both within- and between-run assays. All coefficients of variance were less than 6% and mean relative errors were within +/- 3.75%. The average recovery was 73.77%. The limit of detection and quantitation were 1 ng and 0.02 micrograms/ml, respectively. Application of this method was successfully assessed by intravenous administration of a 15 mg/kg dose of (+)-catechin in rabbits. This new method provides a simple, specific and sensitive determination for (+)-catechin in rabbit plasma and is suitable for pharmacokinetic studies. PMID- 7795817 TI - Determination of the renin inhibitor Ro 42-5892 in human plasma by automated pre column derivatization, reversed-phase high-performance liquid chromatographic separation and electrochemical detection after post-column irradiation. AB - The renin inhibitor Ro 42-5892 has been found to be very potent, thereby necessitating a sensitive assay method for the evaluation of its pharmacokinetics in man. We report here the development of a very sensitive and selective HPLC assay for the analysis of this compound in human plasma. Ro 42-5892 was extracted from plasma with dichloromethane, derivatized with 2,4-dinitrofluorobenzene and then chromatographed on a Novapak C18 column (150 x 3.9 mm I.D.) with acetic acid buffer (pH 7)-acetonitrile (100:85). Detection was performed by irradiation at 254 nm, followed by electrochemical oxidation at 550 mV. The extraction recovery of Ro 42-5892 from human plasma (mean 102%) was quantitative. With this method a limit of quantitation of 0.3 ng/ml was achieved. The assay was linear up to 5 ng/ml, had acceptable inter-assay precision (12.2%) and accuracy (9.3%) and was successfully tested for selectivity. This assay was successfully applied to over 250 samples from a pharmacokinetic study in hypertensive patients. PMID- 7795819 TI - Improved high-performance liquid chromatographic method for the determination of polycyclic aromatic hydrocarbon metabolites in human urine. AB - A reversed-phase HPLC method with fluorescence detection was evaluated for utility in determination of urinary metabolites of polycyclic aromatic hydrocarbons as biomarkers of environmental exposure. The method, which was developed for use in studies of high-level occupational exposure, was found to be unreliable for relatively low-level environmental exposures. The method was modified to include quantitation by standard addition in order to compensate for matrix effects at levels as low as 0.1 ng/ml. The standard addition modification increased both qualitative and quantitative performance, with recovery of 1 hydroxypyrene spikes improved from 164% to 114% at 0.36 ng/ml. The modified method was successfully applied in an environmental exposure study. PMID- 7795820 TI - Possibilities for confirmatory analysis of some beta-agonists using two different derivatives simultaneously. AB - A previously described method for the confirmatory analysis of clenbuterol with chemical ionization GC-MS was extended to fit more beta-agonists. The method has been used routinely for about one year and a large number of samples have been analysed according to the described procedure. This paper summarizes the results obtained with this method with regard to clenbuterol and furthermore discussion is focused on applicability to beta-agonists other than clenbuterol with respect to the European Community requirements for confirmatory analysis. PMID- 7795821 TI - Solid-phase extraction of isosorbide dinitrate and two of its metabolites from plasma for gas chromatographic analysis. AB - A rapid, accurate and selective method for the determination of isosorbide dinitrate and its 2- and 5-isosorbide mononitrate metabolites in 1.0 ml of human plasma has been developed. Before chromatographic quantitation by gas-liquid chromatography with electron-capture detection, the compounds are subjected to solid-phase extraction, using ENVI 18 cartridges (Supelco). The intra-day and inter-day coefficients of variation are less than 10%, except the inter-day coefficient of variation for the assay of 5-isosorbide dinitrate which is less than 15%. Limits of quantitation are 10, 10 and 20 ng/ml for isosorbide dinitrate, 2-isosorbide mononitrate and 5-isosorbide mononitrate, respectively. Recoveries are in excess of 90% for isosorbide dinitrate and 70% for its two metabolites. PMID- 7795823 TI - Simple method for the analysis of tenoxicam in human plasma using high performance liquid chromatography. AB - A simple, rapid and cost-effective method for the determination of tenoxicam in human plasma is described, using ketorolac as the internal standard. The extraction procedure utilised 5% zinc sulphate and methanol. A nucleosil C18 column and 35:65 acetonitrile-water phosphate buffered mobile phase (pH 2.8) were used, with ultraviolet detection at 355 nm. The assay was linear in the range 40 ng/ml-10 micrograms/ml, with recovery of extraction ranging from 87 to 102%. The intra- and inter-assay reproducibility had coefficients of variation of 3.9-7.7 and 1.6% respectively. The limit of detection for this method was 40 ng/ml. PMID- 7795822 TI - Determination of ticlopidine in human plasma by high-performance liquid chromatography and ultraviolet absorbance detection. AB - A simple HPLC method has been developed for the determination of ticlopidine in human plasma. Plasma samples were buffered at pH 9 and extracted with n-heptane isoamyl alcohol (98.5:1.5, v/v). Imipramine was used as internal standard. Chromatography was performed isocratically with acetonitrile-methanol-0.05 M KH2PO4 (20:25:55, v/v) at pH 3.0 containing 3% triethylamine at a flow-rate of 1 ml/min. A reversed-phase column, Supelcosil LC-8-DB, 15 cm x 4.6 mm I.D., 5 microns particle size, was used. The effluent was monitored by UV absorbance detection at 235 nm. The method showed good accuracy, precision and linearity in the concentration range 5-1200 ng/ml. The limit of quantitation was 5 ng/ml, with a precision (C.V.) of 8.91%, which is the same as that achieved by other authors with a previously published GC-MS method. The procedure described in this paper is simple and allows the routine assessment of ticlopidine plasma concentration in pharmacokinetic studies following therapeutic doses in human subjects. PMID- 7795825 TI - A foot in the door. PMID- 7795824 TI - Colors of the spectrum. The challenges of addiction nursing. PMID- 7795826 TI - Management perspectives. I am the head nurse on a very large, and very busy pediatric unit. PMID- 7795827 TI - School-based health services fill a need for disadvantaged youth. PMID- 7795828 TI - Dealing with sexual harassment. PMID- 7795829 TI - Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. AB - Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current consumption. The first experimental diet, arguably termed "ideal," is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommendations to the general public. PMID- 7795830 TI - Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial. AB - National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy. PMID- 7795831 TI - Design of a multicenter trial to evaluate long-term life-style intervention in adults with high-normal blood pressure levels. Trials of Hypertension Prevention (phase II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - Phase II of the Trials of Hypertension Prevention (TOHP) is a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute designed to test whether weight loss alone, sodium reduction alone, or the combination of weight loss and sodium reduction will decrease diastolic (DBP) and systolic blood pressure (SBP) as well as the incidence of hypertension (DBP > or = 90 mm Hg, SBP > or = 140 mm Hg, and/or use of antihypertensive medications) in subjects with high-normal DBP (83 to 89 mm Hg) and SBP less than 140 mm Hg at entry. These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure (BP) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP. The phase II study population is comprised of 2382 participants (1566 men and 816 women) who are 110 to 165% of desirable body weight, allocated at random to the four treatment arms using a 2 x 2 factorial design. The trial has 80% power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups. BP observers are blinded to participant treatment assignments. Participants will be followed for 3 to 4 years. This trial may have important public policy implications concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term, thereby avoiding the need for drug therapy which while effective is costly and may have side effects. PMID- 7795832 TI - Recruitment for phase II of the Trials of Hypertension Prevention. Effective strategies and predictors of randomization. Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - Phase II of the Trials of Hypertension Prevention is a multicenter, randomized, controlled trial designed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure. The 2 x 2 factorial study design includes weight loss alone, restricted sodium intake alone, the combination of weight loss and sodium restriction, and a control group. Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months, which exceeded the sample size goal of 2250. Among randomized participants, 21% were minorities and 34% were women. Overall, direct mail generated the most randomized participants (73%), followed by community screening (12%) and media advertisement (11%). Referrals from community health care providers yielded few participants. Prescreening improved overall efficiency and reduced costs. Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger, single, male, smokers, and less educated. PMID- 7795833 TI - Baseline characteristics of participants in phase II of the Trials of Hypertension Prevention (TOHP II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - Phase II of the Trials of Hypertension Prevention (TOHP II) is a multicenter, controlled clinical trial designed to test whether weight loss, a reduced sodium intake, or a combination of weight loss and a reduced sodium intake will lower blood pressure (BP) and prevent the occurrence of hypertension. The study population consists of middle-aged, moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg. Of the 2382 randomized participants, 816 (34%) are female and 494 (21%) are from a racial or ethnic minority background. At baseline, mean dietary intakes of sodium, based on measurements of 24-hour urinary excretion, were 199 mmol/d in men and 154 mmol/d in women. The average body mass index was 30.9 kg/m2. Across the four randomized groups, there was no substantial imbalance in the distribution of baseline variables; however, the mean age in the four groups was slightly but significantly different (range: 43.2 to 44.2 years, P = 0.02). A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study. Data reported in this article indicate that any subsequent differences in BP among the randomized groups are unlikely to result from maldistribution of known confounding variables at baseline. Finally, because of the high prevalence of overweight and excessive sodium intake in the United States, results from TOHP II should be broadly applicable to the general population. PMID- 7795835 TI - Progress in life-style intervention for prevention and treatment of high blood pressure. PMID- 7795834 TI - Trials of Hypertension Prevention, phase II. Structure and content of the weight loss and dietary sodium reduction interventions. Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - Identifying effective, nonpharmacologic means of preventing or significantly delaying the onset of hypertension would be a major advance in the primary prevention of cardiovascular disease. In the first phase of the Trials of Hypertension Prevention (TOHP I), adults with high-normal diastolic blood pressure were randomly assigned to one of seven nonpharmacologic interventions. Only weight loss and reduction of dietary sodium proved to be effective strategies for reducing blood pressure. The second phase of TOHP (TOHP II) will test the effectiveness of weight loss, reduction of dietary sodium, and their combination of lowering blood pressure and preventing the onset of hypertension over a 3- to 4-year follow-up period. This article describes the three interventions used in TOHP II, methods used to maintain continued participation in this long-term trial, and protocol enhancements designed to maximize intervention effectiveness. PMID- 7795836 TI - The effect of potassium supplementation in persons with a high-normal blood pressure. Results from phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - We conducted a randomized, double-blind, placebo-controlled trial of oral potassium chloride supplementation (60 mmol/d) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg. In the active (n = 178) compared to the placebo (n = 175) treatment group, the urinary potassium level was significantly (p < 0.001) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy, respectively. Compared to placebo, active treatment was associated with a small (mean = 1.8 mm Hg) but significant (p = 0.04) reduction in diastolic blood pressure following 3 months of therapy. Following 6 months, however, this apparent treatment effect had virtually disappeared (mean reduction in diastolic blood pressure = 0.3 mm Hg). There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit. There was a significant, independent, dose response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure (-1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion. PMID- 7795837 TI - Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. AB - Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials. PMID- 7795838 TI - In vivo confocal microscopy of the cornea and tear film. PMID- 7795839 TI - Scanning force microscopy of chromatin fibers in air and in liquid. AB - We have adapted specimen preparation techniques of conventional electron microscopy for visualizing chromatin structures in the scanning force microscope (SFM) in air and in liquid. The beaded substructure of the nucleoprotein filament was obtained after hypotonic lysis of chicken erythrocytes and air drying, whereas supranucleosomal structures were preserved after treatment of cell nuclei with detergent. In the latter case, the nucleosomes were still distinct but appeared more condensed. A modified droplet diffusion-spreading technique of chromatin from Namalwa cells (a human B-lymphoid line) yielded a uniform filamentous morphology and similar fiber appearance. A reversible swelling of spread chromatin was observed upon exposure of air-dried samples to solutions differing in salt concentrations. PMID- 7795840 TI - Effects of brefeldin-A on Golgi morphology in human cultured fibroblasts observed in three-dimensional stereo scanning electron microscopy. AB - Brefeldin A (BFA) has been reported to cause disassembly of the Golgi. We have used three-dimensional (3-D) high-resolution scanning electron microscopy (HRSEM) to investigate these effects in human skin fibroblast cells. The spontaneous reassembly during prolonged exposure to BFA and some effects of forskolin were observed. A BFA concentration of 5 micrograms/ml caused Golgi complexes to become vesicular, resulting in a progressive decrease in the size of the Golgi. Morphologic changes were visible within 2 min of BFA incubation, and by 30 min no identifiable Golgi could be found. Spontaneous reassembly of the Golgi apparatus upon the removal of the BFA or with continued long-term exposure with BFA could not be confirmed. Preliminary experiments with forskolin were not effective in reversing or inhibiting the effects of BFA in human fibroblast cells grown in culture. This inability for spontaneous reassembly and nonreversal by forskolin may reflect a differential effect of BFA in various cell types. HRSEM has proven to be useful for observing 3-D morphologic effects of BFA in Golgi. PMID- 7795841 TI - Culture of Schwann cells from adult animals. PMID- 7795843 TI - Spontaneous pulmonary adenocarcinoma cell shows osseous metaplasia in vivo. PMID- 7795842 TI - Tissue culture of a mixed cell thymic tumor from Xenopus laevis. PMID- 7795844 TI - Glycosylation of antibody in a lectin-resistant human hybridoma is insensitive to glucose. PMID- 7795845 TI - The gap junctional intercellular communication is no prerequisite for the stabilization of xenobiotic metabolizing enzyme activities in primary rat liver parenchymal cells in vitro. AB - In primary monocultures of adult rat liver parenchymal cells (PC), the activities of the xenobiotic metabolizing enzymes microsomal epoxide hydrolase (mEHb), soluble epoxide hydrolase (sEH), glutathione S-transferases (GST), and phenolsulfotransferase (ST) were reduced after 7 d to values below 33% of the initial activities. Furthermore, the gap junctional intercellular communication (GJIC), measured after microinjection by dye transfer, decreased from 90% on Day 1 to undetectable values after 5 d in monoculture. Co-culture of PC with nonparenchymal rat liver epithelial cells (NEC) increased (98% on Day 1) and stabilized (82% on Day 7) the homotypic GJIC of PC. Additionally, most of the measured xenobiotic metabolizing enzyme activities were well stabilized over 1 wk in co-culture. Because GJIC is one of several mechanisms playing an important role in cell differentiation, the importance of GJIC for the stabilization of xenobiotic metabolizing enzymes in PC was investigated. PC in monoculture were, therefore, treated with 2% dimethyl sulfoxide (DMSO), a differentiation promoting factor, and 1,1,1-trichloro-2,2,-bis (p-chlorophenyl) ethane (DDT) (10 micrograms/ml), a liver tumor promotor and inhibitor of GJIC, was given to co cultures of PC with NEC. DMSO significantly stabilized (68% on Day 7), while DDT significantly inhibited (8% on Day 7) homotypic GJIC of PC in the respective culture systems. In contrast, the activities of mEHb, sEH, GST, and ST were not affected in the presence of DMSO or DDT. These results lead to the assumption that the differentiation parameters measured in this study (i.e., homotypic GJIC and the activities of xenobiotic metabolizing enzymes) are independently regulated in adult rat liver PC. PMID- 7795847 TI - Growing a stratified, cornified primary culture of rat keratinocytes with epidermis-like water permeation barrier function. AB - The culture of cutaneous keratinocytes grown on a Puropore nylon microporous membrane at the air-liquid interface has been shown to be similar to the epidermis in a number of molecular and morphologic characteristics but to exhibit a significantly greater degree of tritiated water permeation. Various culture conditions have been altered in an effort to improve the water barrier properties. A Kp value in the range of 5.5 +/- 1.6 x 10(3) has been obtained for 79% of the cultures a) by plating 0.9 x 10(6) viable basal cells on a piece (13 mm diameter) of membrane for 7 days of submerged growth, b) by placing two membranes on two stacked glass fiber filters (47-mm extra-thick) in a culture dish (60 mm) for 14 days of growth at the air-liquid interface, c) by replacing the growth medium, i.e., 1 ml of complete minimum essential medium (CMEM) every 24 h after lifting, d) by using 10% fetal bovine serum (FBS) in the CMEM during the submerged culture period and 15% FBS in the CMEM during the lifted culture period, and e) by adding a dialysis membrane on top and a Puropore nylon membrane below the culture when the cultures were inserted in the permeation cell for testing. The percentage of cultures with this value for Kp can be increased to 90% if only cultures with yellow, smooth, and shiny surfaces are tested. This system should be useful as a replacement for skin in testing the cutaneous permeation of some chemicals. PMID- 7795846 TI - Transforming growth factor-beta inhibition of mineralization by neonatal rat osteoblasts in monolayer and collagen gel culture. AB - The latent form of transforming growth factor-beta (TGF-beta) is a component of the extracellular matrix of bone. The active form, when locally injected in vivo, stimulates both inflammation and ectopic bone formation. The present study was undertaken to determine if TGF-beta also stimulated mineralization by isolated rat calvarial osteoblasts cultured in collagen gels. Gels were used because they should mimic in vivo conditions better than classical monolayer culture. Compared to cells in monolayers, osteoblasts cultured in collagen gels exhibited slower growth, but higher alkaline phosphatase activity and mineral deposition. Cultured cells also synthesized the osteoblast-specific marker, osteocalcin. The increase in osteocalcin in cell layers was parallel to the increase in mineral deposition. In the presence of TGF-beta, neither cell growth nor alkaline phosphatase activity increased. Instead, a small decrease occurred in both parameters when compared to untreated cultures. Accumulation of collagen, the major component of the extracellular matrix where mineralization occurs, was similar in untreated and TGF-beta 1-treated cultures. However, 8 pM TGF-beta 1 dramatically suppressed mineral deposition in both types of cultures. Despite TGF-beta 1 stimulating a fourfold increase in lactic acid, the consequent increase in culture medium acidity did not account for the inhibitory effects of TGF-beta 1 on mineralization. These results demonstrate that collagen gel culture is an improved technique over conventional monolayer culture for demonstrating differentiated osteoblast function and sensitivity to TGF-beta 1. TGF-beta 1, at a concentration that has little effect on cell growth, alkaline phosphatase activity, or collagen accumulation, is a potent inhibitor of mineralization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795848 TI - Alteration of epithelial cell lipid synthesis by N-nitrosonornicotine. AB - Changes in the lipid composition of a cell membrane due to the binding of one cell modulator may affect binding of a second modulator, whether that binding is receptor-mediated (specific) or non-receptor-mediated (nonspecific). Such altered binding interactions have been demonstrated in oral epithelial cells, wherein N nitrosonornicotine (NNN), a nonspecific ligand, enhances phorbol ester binding. To characterize membrane changes that may be responsible for such an effect, the current study examined lipid changes in hamster oral epithelial (HCP) cells associated with NNN binding. HCP cultures at two cell densities, 5 x 10(6) cells/100 mm plate (subconfluent cultures) or 10 x 10(6) cells/100 mm plate (confluent cultures) were incubated in Keratinocyte-Serum-Free Medium and exposed to 10 microM NNN or DMSO (solvent control) for 48 h. Lipids were labeled with 14C acetate, then extracted, separated by thin layer chromatography, and the 14C lipids located by autoradiography and counted. Exposure of subconfluent cultures to NNN for 48 h, with 14C-acetate present during the final 24 h, resulted in altered phospholipid and fatty acid labeling. Phospholipid labeling increased slightly in the presence of NNN compared to controls, while fatty acid labeling showed a modest but significant decrease in the presence of NNN. Similar changes occurred in the confluent cultures. Prelabeling of lipids in subconfluent cultures, followed by exposure to NNN in the absence of radiolabel, resulted in significantly (P < 0.05) greater phospholipid labeling in the presence of NNN compared to control cultures. At the same time, fatty acid labeling decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795849 TI - Ovarian mesothelial and extramesothelial cells in interactive culture. AB - The ovarian mesothelium (OM) represents the tissue of origin of ovarian epithelial cancer. To gain insight into the regulation of this tissue, OM organoids and submesothelial ovarian stromal cells (SC) were isolated from New Zealand White rabbits by a stepwise tissue dispersal technique, while granulosa cells (GC) were aspirated from mature follicles (14 +/- 4 groups/animal). OM and SC dispersal were sequentially accomplished by: a) 1-h incubation in collagenase type I (300 U/ml), gentle scraping of the ovarian surface, and 1 g sedimentation of OM organoids (equivalent to 0.93 +/- 0.40 x 10(6) cells/animal) on 5% bovine serum albumin (BSA); b) 2-h incubation in pronase-collagenase (0.5%-300 U/ml) under periodical resuspension and gentle scraping of SC (1.40 +/- 0.25 x 10(6)/animal) from OM-denuded ovaries. After a week-long in vitro expansion, OM cells (OMC) were cultured alone and with SC or GC within monocameral vessels or bicameral transfilter vessels in serumless, fibronectinrich (4 micrograms/ml) HL 1 medium. After 7 d of contact cell-cell interaction, cytokeratin-positive OMC became surrounded by fibroblastoid, vimentin-positive SC or by cytokeratin and vimentin-weakly positive GC. Filter-bound OMC humorally interacting with underlying SC or GC displayed a biphasic, epithelioid and spindle, morphology with universal cytokeratin expression. Bromo-2'-deoxyuridine (BrdU) immunoperoxidase revealed mean cell proliferation indices of 14.88% for OMC cultured alone, 11.21% and 19.39% for OMC cultured with GC or SC in monocameral dishes, and 15.25% or 22.47% for OMC cultured in bicameral vessels over GC or SC, respectively. This model provides an experimental tool for investigating the unexplored role of stromal-mesothelial interaction in OM pathobiology. PMID- 7795850 TI - In situ fluorescence labeling of sheep lung microvascular endothelium. AB - Endothelial cells are intimately involved in a variety of biological processes such as inflammatory disorders, wound healing, and tumor invasion. The finding of endothelial heterogeneity in various tissues has led to major efforts to isolate and culture microvascular endothelial cells in human and animal tissue. In this report we have used phosphatidyl ethanolamine (PE)-labeled liposomes to fluorescently label the sheep lung microvasculature in situ. Using normotensive perfusion pressure, the PE-labeled liposomes did not extravasate into extravascular lung tissue. Mechanical and enzymatic digestion of the lung tissue demonstrated that the PE-labeled liposomes provided a stable label of the vascular lining cells during ex vivo processing. After digestion, the overwhelming majority of the fluorescent label appeared in cellular aggregates. Approximately 80% of these cells demonstrated an in vitro phenotype consistent with microvascular endothelium. A novel monoclonal antibody selective for sheep endothelial cells was developed to confirm the presence of lung endothelium in the fluorescently labeled cellular aggregates. We conclude that in situ fluorescence labeling of vascular lining cells provides an anatomic marker for relevant vascular lining cells and an opportunity to study these cells in vitro. PMID- 7795852 TI - Initial stability of uncemented hip stems: an in-vitro protocol to measure torsional interface motion. AB - The difficulty in quantitatively assessing the inherent variables of surgical stem insertion and interfemur differences continues to be a problem in experimental methodologies which assess hip stem stability. An in-vitro torsional stability protocol was developed which limited the mechanical testing variability and provided a reproducible micromotion measurement of an uncemented stem in synthetic composite femurs. Using a controlled mechanical stem insertion resulted in less interfemur variability within each group with the coefficient of variation being reduced from 35% overall to less than 20%. Femurs with shallow stem insertion depths had significantly larger micromotion than femurs having deep stem insertion depths. The sensitivity of the experimental protocol and the synthetic composite femurs to the varied functional behaviour of three different stem designs was demonstrated. The stem with a hollowed anterior-to-posterior proximal section experienced significantly more motion than the two stems with full proximal sections, reinforcing the need for proximal contact to ensure minimal micromotion in torsional loading. PMID- 7795853 TI - Estimation of the effective amount entering the body for drugs subject to enterohepatic recirculations. AB - A pharmacokinetic model is used to take into account multiple recirculations of drug occurring at various times after gall bladder emptying. If a dose D is initially administed, due to recirculation, an effective amount A* reaches the body. This value A* is expressed as a function of D and the model parameters, after oral administration or intravenous injection. Using areas under curves in two different situations, the reabsorption rate may be identified. PMID- 7795854 TI - Sensitivity analysis for estimating urea kinetics parameters during hemodialysis. AB - In this paper a time-varying volume, double-pool urea kinetics model is considered and a sensitivity analysis is carried out to determine those patient parameters that have greater influence on the time course of blood urea nitrogen concentration (BUN) during and between dialysis treatment. The model parameters include the urea generation rate, the initial distribution volume of the urea, the ratio between intracellular and extracellular volumes, and the mass transfer coefficient between the two pools. The analysis demonstrates that BUN is highly sensitive to the urea generation rate and total distribution volume whereas it is influenced by the remaining parameters to a much lesser extent. In addition, the location of the absolute maxima of BUN sensitivity functions suggests the rational placement of a reduced number of blood samples that may still allow sufficiently accurate estimates for the parameters of clinical interest, such as the urea generation rate, total distribution volume, and the ratio between intracellular and extracellular volumes. This conclusion has been confirmed by simulation studies where parameter estimation has been performed with a varying number of observation points. PMID- 7795851 TI - Characterization of a rat anterior pituitary cell bioassay. AB - We have described the protocols and characterization of a pituicyte culture, which became established as a reliable and reproducible bioassay for the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The bioassay was used to measure the bioactivity of factors that inhibit and stimulate gonadotrophin secretion. The protocol that was used involved the culling of female Wistar rats (200 to 250 g weight), at random stages of their cycle, and dispersal of their pituicytes in a concentration of 0.4 x 10(6) cells.ml-1.well-1 in serum-free medium (Dulbecco's modified Eagle's medium/Ham's F12 mixture, supplemented with insulin and transferrin) in Falcon 3047 24-well culture plates. After 24 h of pre-culture, the medium was changed and the cells cultured for a further 48 h. The supernatant was removed and assayed for basal secretion of FSH and LH. The cells were then stimulated with 10(-8) M GnRH for 4 h and the supernatant assayed for gonadotrophin-releasing hormone (GnRH) stimulated FSH and LH secretion. All samples were assayed as pairs of duplicates (i.e. quadruplicate samples) which were randomly added to the plates to minimize plate effects. Random number tables were used to achieve this randomization. PMID- 7795855 TI - Alignment of total knee arthroplasty: the relationship to radiolucency around the tibial component. AB - Between January 1982 and July 1985, 122 cemented 'Accord' total knee replacements were performed. Out of this number, 21 were lost to follow-up because of death (in 16), revision (2) due to infection, and failure to attend (3). The post operative alignment of 101 prostheses were compared to the incidence of radiolucencies around the tibial component at 5 years follow-up. The mechanical axis was used as a reference. The mean alignment was 0.99 degrees valgus with a standard deviation of 2.48 degrees. Some 72% of knees were within 3 degrees and 94% within 5 degrees of true alignment. Using two methods of assessing radiolucencies there was a non-significant relationship between the alignment and radiolucencies. The alignment tolerance with this prosthesis is, therefore, at least 5 degrees. PMID- 7795856 TI - Iterative method to derive an approximate matched filter template for fetal electrocardiogram signals. AB - Fetal electrocardiogram (FECG) signals that are extracted from the maternal abdomen have a signal-to-noise ratio that is so low that the determination of the times of location of the R-waves can be difficult. A matched filter could, in principle, be used, but in theory this requires prior knowledge of the shape of the QRS complex of the FECG. In the work that is described in this paper, a digital low-pass filter, with an impulse response that is triangular in shape, is applied to the first M complexes of a simulated FECG signal. An average based on the detected R-wave locations is determined and this is used as an approximation to the matched filter template for the next block of M complexes. It is shown that this method can be iterated to obtain an effectiveness in detecting R-wave locations that is competitive with the corresponding performance that is obtained with the pure matched filter. The resilience of this technique to increasing noise levels is investigated. PMID- 7795857 TI - A dynamic Fourier series for the compression of ECG using FFT and adaptive coefficient estimation. AB - In this article, a new ECG data compression technique is proposed. The method relies on modelling quasi-periodic ECG signals as a dynamic Fourier series. Fourier coefficients are continuously estimated using either an FFT algorithm or the adaptive least mean square algorithm. Results from simulated normal and pathological ECGs are presented and discussed. The merits of each of the above two methods are also illustrated. Furthermore, a comparison with other compression techniques is also discussed. PMID- 7795859 TI - Validation of a computer model of haemorrhage and transcapillary refill. AB - A computer model is described which uses blood volume deficit and its duration to simulate the first two hours of haemorrhage, including an estimation of the blood volume added by Starlings transcapillary refill mechanism. Computer prediction of the haematocrit was compared with published data on haemorrhage in animals. There was close correlation with data on the haemodilution caused by Starling's transcapillary refill mechanism in conscious swine (r = 0.84). PMID- 7795858 TI - A mathematical analysis of intestinal peristaltic waves. AB - Gut motility is usually investigated by introducing probes in the intestinal lumen. Image analysis could be used instead of intraluminal pressure measurements to avoid the inconvenience of this invasive procedure. The present study exposes the theoretical principles of intestinal peristalsis in terms of indirect intraluminal pressure and content velocity measurements. A geometrical model of intestinal contractions is mathematically described by using Stokes' equations in order to evaluate velocities and pressures in the equations established by quantitative analysis of cinematography pictures. The couple velocity-pressure is calculated at each point of the geometrical model for a viscous and non compressible fluid. This fluid flows in a geometrical structure, the boundaries of which vary with time and behave in a periodic and regular way by simulating the movements of intestinal contractions. A comparison is made between experimental pressure recordings in isolated rat intestines and pressure values calculated by utilizing the geometrical model. Velocity values calculated at every grid node show positive and negative zones in the geometrical model output. The position of these zones vary from one geometrical model to another. Moreover, the calculated pressure and velocity values change according to the applied vector efforts. The similarity of the results obtained shows the efficiency of the finite element technique in the case of Stokes' equations. PMID- 7795860 TI - Non-invasive identification of gastric contractions from surface electrogastrogram using back-propagation neural networks. AB - Gastric contractions play an important role in the digestive process of the stomach. The established method for the measurement of gastric contractions is invasive and involves the insertion through the nose of a manometric probe into the stomach. A non-invasive method is introduced in this paper for the identification of gastric contractions using the surface electrogastrogram. The electrogastrogram (EGG) was measured by placing surface electrodes on the abdominal skin over the stomach in ten subjects. Gastric contractions were simultaneously monitored using an intraluminal manometric probe. The back propagation neural network was applied to identify gastric contractions from the EGG. The input of the neural network was composed of spectral data points of the EGG which was computed using the exponential distribution method. Experiments were conducted to optimize network structures and parameters. Using the EGG data in five subjects as the training set and the EGG data in another five subjects as the testing set, an overall accuracy of 92% was achieved in the identification of gastric contractions with an optimized three-layer back-propagation neural network (number of nodes for input:hidden:output layers being 64:10:2). PMID- 7795861 TI - Fading characteristics of a 2.3 GHz radio telemetry channel in a hospital building. AB - This paper reports on radio path attenuation measurements made in a hospital complex at a spot frequency of 2.340 GHz. Power loss figures for fixed path propagation in a variety of building types have been determined for proposed telemetry use in operational ward situations. Throughout the hospital, the radio paths assessed all exhibited a loss in excess of that calculated for free-space communications. Modern buildings had external wall losses of 10-25 dB, with dividing walls in wards contributing an additional 5 dB. Received signal strength levels indicated a Rayleigh distribution for obstructed paths. Temporal testing was used to find the rate and depth of signal fades caused by the movement of personnel and equipment during normal ward usage; signal level reductions of greater than 35 dB were common during busy periods. PMID- 7795862 TI - Improved late potential analysis in frequency domain. AB - This work presents a technique to improve the identification of late potentials (LP) in patients affected by greater arrhythmogenic right ventricular disease (GARVD). Several authors have documented the correlation between GARVD and LP by means of time domain analysis. Moreover, the high incidence of bundle branch block in patients affected by GARVD suggests LP analysis in the frequency domain be performed. The method of spectral mapping of the ECG with Fourier transform was adopted. This consists in dividing the ST segment into 25 subsegments and estimating their frequency components by means of the fast Fourier transform. Recently, it was documented that this technique suffers from poor reproducibility of results. Low reproducibility is the consequence of an improper localization of the analysed QRS segments. An algorithm to increase the QRS end point identification reproducibility is proposed. An optimal QRS filter was adopted as well as a technique based on the Hilbert transform. This technique allowed the reliability of the normality factor estimates to be improved. The computed normality factors on the XYZ leads and on the vector magnitude were used to classify patients and healthy subjects; 28 patients affected by greater arrhythmogenic right ventricular disease and 35 healthy subjects were analysed in the study. High sensitivity was obtained with respect to GARVD and clinical sustained ventricular tachycardia by means of a cluster analysis technique. By applying the technique proposed in this paper the identification of LP in GARVD was increased from 47% to 88%, when clinical sustained ventricular tachycardia was documented, whereas in patients affected by GARVD but not prone to sustained ventricular tachycardia LP identification increases from 18% to 64%. PMID- 7795863 TI - Risk factors associated with having a pressure ulcer: a secondary data analysis. AB - Data obtained through five hospital-wide pressure ulcer audits were pooled for exploratory analysis. The purpose of this secondary data analysis was (1) to delineate the association of various risk factors and the presence of pressure ulcers and (2) to generate specific, testable hypotheses. Risk factors studied included fecal incontinence, urinary incontinence, malnutrition, impaired mobility, decreased mental status, diabetes mellitus, peripheral vascular disease, spinal cord injury, multiple sclerosis, and metastatic carcinoma. Stepwise logistic regression resulted in a best-fitting model that included fecal incontinence, impaired mobility, malnutrition, decreased mental status, and an interaction effect between fecal incontinence and impaired mobility. This model suggested that the odds of having a pressure ulcer were 22 times greater for hospitalized adult patients with fecal incontinence compared to hospitalized adult patients without fecal incontinence. PMID- 7795864 TI - Tracking the diabetic foot: adjunctive treatment with collagen material. AB - Many people with diabetes mellitus have foot lesions that can lead to amputation if they do not receive excellent care. Coordinating patient care with other specialists, using new treatment technology, educating the patient, and including the patient as a significant part of the team are all required for effective patient care. The use of a new, technologically advanced product, Kollagen, is illustrated in two case studies. Collagen plays a significant part in almost every function of the body. Previously, the broad use of collagen was stifled because of cost. Recent advances have made it possible to develop cost-effective gels, powders, pouches, and thin dressings. PMID- 7795865 TI - Comparative ability of various prescription and over-the-counter topical antifungal drug products to inhibit the growth of C. albicans. AB - On September 23, 1993, the Food and Drug Administration (FDA) published the final monograph and rule for topical antifungal drug products. This monograph specifies the ingredients, concentration, and labeling under which over-the-counter (OTC) topical antifungal drug products may be marketed without further FDA approval. Currently, the nine products tested are labeled as antifungal because of their ability to inhibit the growth of yeast (C. albicans) in vitro. Over-the-counter products containing 2% miconazole nitrate--an ingredient and concentration identified as safe and effective--were found to inhibit the growth of C. albicans as effectively as mycostatin cream. Two percent miconazole nitrate was also inhibitory to C. albicans at greater dilutions than five other antifungal products containing chloroxylenol and clotri mazole. Chloroxylenol and clotrimazole are nonmonographed ingredients. PMID- 7795867 TI - Continuum of care. PMID- 7795866 TI - Pressure ulcer incidence on a spinal cord injury unit. AB - Because of the high risk for pressure ulcers among hospitalized, spinal cord injured patients, one quality improvement measure is to monitor incidence of pressure ulcers. A retrospective chart review of each patient who developed an ulcer during an 18-month period revealed patient characteristics associated with pressure ulcer risk. Of 468 inpatient admissions, 35 patients developed 81 pressure ulcers. Patient variables associated with an incidence rate of 7.5% were an admission diagnosis of pressure ulcer, surgical repair of pressure ulcers, length of stay, new spinal cord injury, longstanding injury (> 10 years), and the use of condom catheters. PMID- 7795868 TI - Pressure ulcers: no more excuses-assess institutions instead of patients. PMID- 7795869 TI - Critical paths for wound care. AB - Critical paths and clinical algorithms are an adjunct for quality management of an average person's health problems. A critical path attempts to achieve continuous quality improvement by aligning actions of the care team. Critical paths are difficult to construct for chronically ill patients with comorbidities. Therefore, clinicians are challenged to consider key elements of critical paths: describing normalcy, identifying variances, creating differential diagnoses, handling individual responses to care, managing continuity of care, communicating among team members, discerning chronic disease dilemmas, and developing a common pathway model. Continuity of care and cost effectiveness can be the result of close attention to aspects of critical pathways. Medicine is frequently described as art blended with science. Nowhere is the art of medicine more apparent than in the management of wounds. The challenge of wound care has taxed the ingenuity of countless caregivers from the days when therapeutic armaments consisted of only salves, balms, and poultices to the present plethora of high-tech therapies. Unfortunately, the treatment of patients with wounds for the most part has been relegated to a little-appreciated segment of an equally unappreciated and "unattractive" category of chronic disease. PMID- 7795872 TI - Template for pressure ulcer research. AB - Synthesizing scientific information from the literature, even in a well-defined area, is difficult because not all studies report similar information. A template was developed by the authors to abstract information from articles reviewed for the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline on Pressure Ulcer Treatment. The research template specifies content to be included in a study reprot (e.g. variables, methods, endpoints, statistics, and conclusions). The authors also propose the use of the template to guide researchers so that future studies include important elements and provide greater methodologic consistency. PMID- 7795871 TI - AHCPR treatment guideline for pressure ulcers. PMID- 7795870 TI - The cost of treating pressure ulcers following implementation of a research-based skin care protocol in a long-term care facility. AB - Although concern for the costs associated with pressure ulcer treatments persists, studies that precisely quantify costs are limited. A retrospective research design was used to describe the costs incurred by an 830-bed, long-term care facility to treat 81 pressure ulcers over a one-year period following implementation of a research-based, skin care protocol. The total cost for the study period was $30,079 with 73% of these expenditures attributable to nursing care. Mean cost of treatment was $3.74/pressure ulcer/day, which was a reduction from the $5.35/pressure ulcer/day cost prior to implementation of the skin care protocol. These findings suggest that implementing a research-based, skin care protocol can promote a reduction in treatment costs. PMID- 7795873 TI - Evaluation of the effectiveness of two support surfaces following myocutaneous flap surgery. AB - Recurrence of pressure ulcers is a serious problem following myocutaneous flap surgery and can lead to prolonged and expensive hospitalization. One of the most important aspects of patient care after surgery is the monitoring of reduced pressure in the area of the flap. Usually reducing pressure requires an expensive high-tech support surface. The purpose of this study was to evaluate the effectiveness of a less expensive support surface. There were 12 patients involved in a clinical trial that lasted 14 days and compared the effectiveness of the ROHO dry-floatation mattress to that of the Clinitron bed. Findings indicated that post-operative patients were effectively treated on either support surface. PMID- 7795876 TI - Wound care products resource. PMID- 7795874 TI - Nursing and industry: a time for collaboration. AB - Collaboration between industry and clinical sites is an excellent way to foster research and improve patient care. A seven-step program for collaboration was illustrated by a clinical trial of a new dressing, Ventex (Kendall Health Care Products Co.). The seven steps are (1) Establish basis for collaboration; (2)sign agreements or contracts; (3) develop a project plan; (4) develop the protocol; (5) implement the study; (6) analyze the data and report results; and (7) present conclusions and publish results. Dressing performance, clinician and patient acceptance, and healing indicate that the dressing is feasible for a variety of wounds in a variety of settings. PMID- 7795875 TI - A review of the skin and its appendages. AB - Descriptions of the skin and its appendages tend to be a repetition of the basic facts well known by most clinicians. This article provides a more in-depth description of the epidermal cell layers, the dermis, and the appendages, as well as migrating cells, collagen, mast cells, macrophages, and lymphocytes. The appendages--hair, nails, sweat and sebaceous glands, and sensory receptors--are also described in depth. PMID- 7795877 TI - Nurses' knowledge of pressure ulcer prevention, staging, and description. AB - The purpose of this study was to examine registered nurses' (N = 228) knowledge of pressure ulcer prevention, pressure ulcer staging, and wound description. A 47 item, true-false Pressure Ulcer Knowledge Test was developed for he study. Nurses' knowledge was significantly higher the more recently they had heard a lecture or read an article about pressure ulcers. Knowledge scores were not related to educational background, age, or years of work experience. PMID- 7795878 TI - Applicants needed for research funds. PMID- 7795879 TI - Questions about antifungal drug products. PMID- 7795880 TI - Efficacy of a comprehensive pressure ulcer prevention program in an extended care facility. AB - The effects of a comprehensive pressure ulcer prevention program on the incidence of nosocomial skin breakdown and cost effectiveness were evaluated in this 8 month prospective study and follow-up after an 11-month interval. Baseline data were collected on all residents of a 125-bed nursing home who were present at the study start or were subsequently admitted during the initial 8-month interval. Reassessments were conducted on all residents at 2-month intervals during the initial 8-month study period. New admissions were similarly assessed. The program, which was modeled in accordance with the AHCPR's guideline on pressure ulcers, was implemented after staff education and a 2-month evaluation of residents. A total of 241 residents were entered in the study, the majority of whom were female, incontinent, and at high risk for pressure ulcers. After program implementation, the incidence of pressure ulcers decreased significantly (p < .001) at each of the four initial post-program measurement periods and the 11-month follow-up. The cost analysis for the 8-month study period revealed savings that totalled more than $230,000 for the prevention program versus treatment costs. Findings support the implementation of comprehensive pressure ulcer prevention programs in extended care facilities to decrease the dollar cost of care and the cost of human suffering with a pressure ulcer. PMID- 7795881 TI - An essay on the science of reimbursement. PMID- 7795882 TI - Basement membrane (type IV) collagen. AB - The collagen IV molecule is 400 nm long and consists of two alpha 1 (IV) and one alpha 2 (IV) chains. Their genes COL4A1 and COL4A2 form a transcription unit in which they are arranged head-to-head and connected by a short common promoter region. Recently, four additional genes have been discovered. They are similarly arranged in the pairs COL4A3-A4 and COL4A5-A6 and code for additional collagen IV isoforms. in the macromolecular network of collagen IV, which provides the scaffold for basement membranes, the molecules are attached and cross-linked via their like end-regions and they interact laterally with their triple-helical domains in a not yet fully understood manner. Collagen IV is involved in interactions with cells and possesses two specific recognition sites for the integrins alpha 1 beta 1 and alpha 2 beta 1. PMID- 7795883 TI - Cloning and expression of laminin alpha 2 chain (M-chain) in the mouse. AB - Laminins are a family of heterotrimeric glycoproteins specific to basement membranes. Laminin-2, consisting of alpha 2, beta 1 and gamma 1 chains, was originally identified in the basement membranes of skeletal muscle and peripheral nerve. We have isolated and sequenced the full-length cDNA for the mouse laminin alpha 2 chain. Four overlapping clones spanning 9,330 bp encode a predicted polypeptide of 3,106 amino acids having a calculated molecular mass of 390 kDa including a 23-amino-acid signal peptide. The amino acid sequence of the alpha 2 chain shares a 45.9% identify with that of the alpha 1 chain. Similar to the structure of the alpha 1 chain, the alpha 2 chain consists of several domains beginning at the N-terminus with three globular domains alternating with three epidermal growth factor-like domains followed by two alpha-helical domains and a C-terminal globular domain. The most N-terminal globular domain is highly conserved (77.3% identity) between the alpha 2 and alpha 1 chains, whereas the alpha-helical domains have low homology (30.3% identity). Northern blot and ribonuclease protection analysis revealed expression of mRNA for the alpha 2 chain in heart, kidney, liver, skin, lung and skeletal muscle of newborn mice. such a tissue distribution suggests a role for the alpha 2 chain and, consequently, laminin-2 or -4 not only in the organization and the function of nerve and muscle tissue but possibly also in the mesenchymal components of certain tissues. PMID- 7795885 TI - A quantitative analysis of the incorporation of fibulin-1 into extracellular matrix indicates that fibronectin assembly is required. AB - Fibulin-1 is an extracellular matrix glycoprotein found in both loose and dense connective tissues, elastic fibers and some basement membranes. Cultured cells such as fibroblasts assemble endogenously synthesized or exogenously added fibulin-1 into matrix fibrils that also contain fibronectin. Since we have previously shown that fibulin-1 binds to fibronectin (Balbona, K., Tran, H., Godyna, S., Ingham, K. C., Strickland, D. K. and Argraves, W. S. J. Biol. Chem. 267: 20120-20125, 1992), we sought to investigate fibulin-1 incorporation into fibroblast extracellular matrix with an emphasis on evaluating the potential role of fibronectin in the process. In this study, we have used quantitative assays to measure the binding of 125I-fibulin to monolayers of cultured fibroblasts. Our results show that the kinetics of fibulin-1 incorporation into the cell layer and its partitioning into detergent-soluble and -insoluble fractions were similar to those of fibronectin. It was found that antibodies to fibronectin or to the fibulin-1-binding domain of fibronectin-inhibited fibulin-1 incorporation. Cell lines that fail to assemble fibronectin into the matrix, such as HT1080 or PFHR 9, do not incorporate fibulin-1 into their cell layers. However, when HT1080 cells were induced to assemble fibronectin by treatment with dexamethasone, they subsequently acquired the ability to incorporate fibulin-1. Moreover, treatment of cultured fibroblasts with antibodies that inhibit fibronectin assembly significantly inhibit fibulin-1 incorporation into the matrix. When increased amounts of fibronectin were incorporated into cells layers by incubating the cells for varying lengths of time with exogenous fibronectin, a corresponding increase in fibulin-1 incorporation was also observed. Taken together, the data indicate that the incorporation of fibulin-1 requires fibronectin assembly and suggests a dependence on the amount of fibronectin in a matrix. These results highlight the potential of fibronectin to control the deposition of fibulin-1 into those extracellular matrices where both proteins coincide and may have implications in the formation of fibulin-1-containing matrix structures such as basement membranes or elastic fibers. PMID- 7795886 TI - Identification and characterization of human tissue inhibitor of metalloproteinase-3 and detection of three additional metalloproteinase inhibitor activities in extracellular matrix. AB - We have identified and characterized a novel human tissue inhibitor of metalloproteinase (TIMP). It is found exclusively in the extracellular matrix of a large number of cultured human cells, including: primary embryonal kidney (293), neuroblastoma (SK-N-SH), normal whole embryo (FHs 173We), cervical carcinoma (HeLa S3), colon adenocarcinoma (Caco-2), ileocecal adenocarcinoma (HCT 8), fibrosarcomas (SW 684 and Hs 913T) and normal gingival fibroblasts (GF11 and 1292). It was not detected in the conditioned media from any of these cell lines. Its apparent molecular mass of 24-25 kDa, as determined by its migration on protease-substrate gels, is intermediate between TIMP-1 (28.5 kDa) and TIMP-2 (21 kDa). Like the latter two proteins, human TIMP-3 contains intrachain disulfide bonds and displays altered electrophoretic mobility in the presence of beta mercaptoethanol. The N-terminal, amino acid sequence of the protein is identical to that of chicken TIMP-3 (ChIMP-3), and its amino acid composition is similar. The protein is not N-glycosylated, as determined by treatment with N-glycosidase F. Finally, it is recognized by antisera raised against pure ChIMP-3 but not by anti-human TIMP-1 or anti-human TIMP-2 antibodies. Based on these properties, we propose that this protein is TIMP-3 and is the human counterpart of ChIMP-3 (Pavloff et al., J. Biol. Chem. 267: 17321-17326, 1992). Two additional inhibitors detected in the matrix of human cell lines, designated inhibitor of metalloproteinase (IMP)-a and IMP-b, migrate with apparent masses of 29 kDa and 30 kDa. Both are N-glycosylated. A fourth inhibitor activity, which is smaller in mass than TIMP-3 and is also pecifically located in the matrix, is detectable in some cell lines. PMID- 7795884 TI - Perlecan in human bone marrow: a growth-factor-presenting, but anti-adhesive, extracellular matrix component for hematopoietic cells. AB - Human perlecan is a heparan sulfate proteoglycan with a large core protein of 467 kDa to which three glycosaminoglycan side chains are attached. It belongs to the heparan sulfate proteoglycan family which has been implicated in strong interactions between developing hematopoietic cells and their microenvironment in the bone marrow. Here we report that perlecan is highly expressed in the human bone marrow, as well as in long-term bone marrow cultures which are thought to mimic hematopoiesis in vitro. Expression of perlecan in this tissue was shown by Northern blotting of the 14-kb mRNA of the core protein and by immunofluorescence stainings. Functionally, perlecan shows a strong anti-adhesive effect on unfractionated bone marrow cells and on various hematopoietic cell lines, repelling the cells from the perlecan-coated area. In contrast, perlecan is adhesive for fibroblasts and endothelial cells. It is suggested that the anti adhesive site is located within the core protein of perlecan since heparitinase treated perlecan still shows the repellent effect. Although anti-adhesive for hematopoietic cells, perlecan is able to bind growth factors like granulocyte/macrophage-colony stimulating factor and present them to hematopoietic progenitor cells in a semi-solid colony assay. The functional role of a growth-factor-binding extracellular matrix component in the bone marrow microenvironment with anti-adhesive properties is uncertain but may be related to compartmentalization. PMID- 7795888 TI - Type VI collagen beaded microfibrils from bovine cornea depolymerize at acidic pH, and depolymerization and polymerization are not influenced by hyaluronan. AB - Type VI collagen beaded microfibrils were extracted from bovine cornea or pig cartilage by limited collagenase digestion. Depolymerization of the microfibril, without strong denaturing reagents linke guanidinium hydrochloride or urea under mild acidic conditions, led to single tetramers and multiples of two to three. However, hyaluronidase digestion in accordance with a published method (Kielty et al. J. Cell Biol. 118:979-990, 1992) was unsuccessful in depolymerizing type VI collagen microfibrils. Also, repolymerization into microfibrils by incubation with hyaluronan was not observed. We further found no binding of native type VI collagen microfibrils to a hyaluronan-Sepharose column. Although a recombinant fragment comprising alpha 3(VI) domains N9-N2 showed apparent binding to the column, electron microscopy did not give any indication of binding of either type VI collagen or fragment N9-N2 to hyaluronan. The present findings suggest that the role of hyaluronan in polymerization of type VI collagen has been overestimated in previous work. PMID- 7795887 TI - The human laminin beta 2 chain (S-laminin): structure, expression in fetal tissues and chromosomal assignment of the LAMB2 gene. AB - The sequence of the human laminin beta 2 chain (previously s-laminin) was derived from cloned cDNAs. The complete translation product has 1798 amino acid residues, including a 32-residue signal peptide. The human chain lacks the tripeptide sequence LRE in domain I which is present in the rat polypeptide chain and has been shown to promote motor neuronal cell adhesion. The human gene (LAMB2) was localized to chromosome 3p21 using somatic cell hybrids and fluorescent in situ hybridization analysis. Northern and in situ hybridization analyses from numerous fetal tissues revealed that the beta 2 chain is generally widely expressed. beta 2, but not beta 1, was shown by in situ hybridization to be expressed in fetal brain and renal glomeruli. In fetal skin, beta 2 was expressed both in epidermal and dermal cells, while beta 1 was expressed only in the dermis. Expression of beta 2 in fetal liver was seen in hepatocytes, while no signals were observed for beta 1. In lung, both beta 1 and beta 2 were expressed in alveoli and bronchial smooth muscle cells, whereas only the beta 2 chain was expressed in bronchial epithelial cells. In striated muscle, however, the beta 1 chain, but not beta 2, was expressed. These results indicate different biological roles for the laminin beta 1 and beta 2 chains. PMID- 7795889 TI - Crystallization studies on avian eggshell membranes: implications for the molecular factors controlling eggshell formation. AB - The avian eggshell is a natural biopolymer and mineral composite. It is a very useful model for biomimetic mineralization, since it is among the fastest forming hard tissues known. Isolated eggshell membranes, which were demineralized in vitro, were used to investigate the in vitro modulation of CaCO3 crystal deposition by organic matrix materials. Crystallization on the demineralized eggshell membrane occurred almost exclusively at the peripheries of residual calcium reserve assemblies, which contain a high concentration of sulfur. Similar structures are observed for eggshell membranes after natural demineralization. The characteristic rhombohedral crystal morphologies of the calcite crystals grown in this in vitro system are much less regular when grown in the presence of organic matrix or partially purified dermatan sulfate proteoglycans obtained from the eggshell. The effect of these macromolecules on the morphology and size of CaCO3 crystals is concentration-dependent. These studies indicate the complexity of the molecular and ionic interactions involved in the initiation and formation of the eggshell, with the focus on the role of the organic matrix. PMID- 7795890 TI - Fatal familial insomnia: sleep, neuroendocrine and vegetative alterations. AB - Fatal Familial Insomnia (FFI) is an autosomal dominant prion disease, characterized by prominent degeneration of the thalamus and involving impaired control of the sleep-wake cycle and of autonomic and endocrine functions. Profound alterations in the sleep-wake cycle consist of progressive decrease or complete absence of sleep activity and loss of any intrinsic cyclic organization of residual sleep. Unbalanced sympathergic activation with preserved parasympathetic drive, associated with chronic secondary hypertension and loss of the physiological nocturnal decrease in blood pressure constitute the characteristic autonomic changes. Neuroendocrine studies document hypercortisolism with abnormal feed-back suppression of adrenocorticotrophic hormone, constantly elevated catecholamine levels and abnormal secretory patterns of growth hormone, prolactin and melatonin. Advanced stages of the disease are invariably characterized by the disappearance of any circadian autonomic and neuroendocrine rhythmicity. FFI represents a model disease emphasizing the correlations among the different sleep, autonomic and neuroendocrine functions. Clinico-pathological correlations demonstrate the role of the thalamus as an integrative neural structure placed between the limbic system and the hypothalamus and controlling the homeostatic balance of the organism. PMID- 7795892 TI - Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. AB - The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS. PMID- 7795893 TI - Sleep as a neuroimmune phenomenon: a brief historical perspective. PMID- 7795891 TI - Narcolepsy and immunity. AB - Narcolepsy is a neurological disorder known to be associated with human leukocyte antigen (HLA)-DQB1*0602 in humans. In a canine model, the disorder is also genetically linked to a gene of high homology with the human mu-switch-like immunoglobulin (Ig) gene (current LOD score 13.6 at 0% recombination). Since association with HLA or other immune function polymorphic genes (T cell receptor of Ig, mainly) is a hallmark of most autoimmune diseases, it is proposed that autoimmunity may also play a role in the development of narcolepsy. Arguments for and against this hypothesis are reviewed. It is shown that both on the basis of the most recent molecular studies, and because of some of its clinical features, narcolepsy may be an autoimmune disorder. However, neither systemic nor central nervous system (CNS) evidence of any autoimmune abnormality have ever been found. To reconcile this discrepancy, it is suggested that the pathological immune process involved in narcolepsy could be difficult to detect because it is restricted to a very small region of the brain or targets a low abundance neuroeffector. Alternatively, it is possible that a more fundamental relationship is involved between sleep generation and immune regulation. The pathophysiology of narcolepsy may then involve new CNS-immune mechanisms that may shed new light on the sleep process itself. PMID- 7795894 TI - Lentiviral infection, immune response peptides and sleep. AB - The aberrant sleep documented in subjects with human immunodeficiency virus (HIV) infection is uniquely important because of the contribution this poor quality sleep makes to the fatigue, disability, and eventual unemployment that befalls these patients. Especially given this importance in clinical care, the research on the prominent sleep changes described in HIV infection remains modest in quantity. The chronic asymptomatic stage of HIV infection is associated with the most intriguing and singular sleep structure changes. Especially robust is the increase in slow wave sleep, particularly in latter portions of the sleep period. This finding is rare in other primary or secondary sleep disorders. The sleep structure alterations are among the most replicable of several pathophysiological sequelae in the brain associated with early HIV infection. It is unlikely that these sleep architecture changes are psychosocial in etiology, and they occur before medical pathology is evident. They are not associated with stress, anxiety, or depression. Evidence is accumulating to support a role for the somnogenic immune peptides tumor necrosis factor (TNF)alpha and interleukin (IL-1 beta) in the sleep changes and fatigue commonly seen in HIV infection. These peptides are elevated in the blood of HIV-infected individuals, and are somnogenic in clinical use and animal models. The peripheral production of these peptides may also have a role in the regulation of normal sleep physiology. The lentivirus family contains both HIV and the feline immunodeficiency virus (FIV). The use of the FIV model of HIV infection may provide a way to further investigate the mechanism of a neurotropic, neurotoxic virus initiating the immune acute phase response and affecting sleep. Neurotropic lentivirus infection is a microbiological probe facilitating neuroimmune investigation. PMID- 7795895 TI - Sleep, sleep deprivation and infectious disease: studies in animals. AB - Common perceptions that the desire for sleep is increased during mild infectious diseases like colds and 'the flu' have fostered beliefs that sleep promotes recovery from infectious disease and that lack of sleep increases susceptibility to infections. However, until recently, the relationship between infectious disease and vigilance received relatively little systematic study. At present, several model systems provide evidence that infectious disease is accompanied by alterations in sleep. Indeed, increased sleepiness, like fever and anorexia, may be viewed as a facet of the acute phase response to infectious challenge. Recent studies also suggest that sleep, sleep deprivation and infectious disease may be related via mechanisms of the immune system (Fig. 1). Data are now accumulating to address questions such as whether immune processes alter sleep, whether sleep or sleep deprivation influences immune competence, and whether sleep facilitates recovery from infectious disease. PMID- 7795897 TI - Chromaffin cell survival prolonged by nerve growth factor from pretransected sciatic nerve. PMID- 7795896 TI - Cell therapy with encapsulated xenogeneic tumor cells secreting beta-endorphin for treatment of peripheral pain. AB - The purpose of this study was to assess whether xenogeneic tumor cells secreting beta-endorphin and immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the spinal cerebro-spinal fluid (CSF) space of rats. Also, a silicone container for polymer capsules was designed for the clinical application of this method of cell therapy. The mouse tumor cell lines, proopiomelanocortin gene transfected Neuro2A which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6)/mL, and transplanted into the spinal CSF space from the occipito-atlantal junction of male Sprague Dawley rats. Three analgesiometric tests--the tail pinch test, the hot plate test, and electrical stimulation test--showed that the rats with encapsulated Neuro2A (n = 6) were significantly less sensitive to pain after transplantation than control animals (n = 8). The analgesia induced by the encapsulated cells secreting beta-endorphin was attenuated by the opiate antagonist naloxone. Morphological study revealed that the encapsulated cells survived for 1 mo after transplantation into the CSF space. An in vitro experiment on cultured capsules (3 cm long) with a silicone container (Kaneka Medics Co) showed that the encapsulated Neuro2A (5 x 10(6) mL) could secrete peptides for 1 mo. The results of this study indicate that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and that a silicone container may help the application of this method to the treatment of cancer pain. PMID- 7795898 TI - Preliminary results of gene transfer to central nervous system by continuous injection of DNA-liposome complex. PMID- 7795899 TI - Delivery of neurotrophic factors to the CNS using encapsulated cells: developing treatments for neurodegenerative diseases. PMID- 7795900 TI - Ammonia removal activity of agarose-encapsulated rat hepatocytes. PMID- 7795901 TI - Recent topics in the management of pain: development of the concept of preemptive analgesia. AB - Recent studies concerned with the relationship between injury responses and acute and chronic pain were reviewed. Basic and clinical studies of pain have revealed that a large proportion of the mechanisms that produce strange signs and symptoms, such as allodynia, hyperalgesia and hyperpathia, after tissue injury are ascribed to increased excitability, or to sensitization derived from biological changes in spinal dorsal horn cells subjected to excessive noxious stimuli from injured tissues. Preemptive analgesia has been under consideration as a means of preventing the predictable sensitization to pain that follows surgery. The findings of many clinical investigations, however, remain controversial. This report discusses the importance of preemptive analgesia including the possibilities of prevention, and of extension to the control, of chronic pain syndromes. PMID- 7795902 TI - Long-term developmental expression and inductivity of cytochrome P450s within intrasplenically transplanted fetal hepatocytes from spontaneously hypertensive rats. PMID- 7795903 TI - Proliferative activity of rat hepatocytes transplanted into the spleen. PMID- 7795904 TI - Long-term effect of intrasplenic hepatocyte transplantation in congenitally ascorbic acid biosynthetic enzyme-deficient rats. PMID- 7795905 TI - Analysis of survival of allogeneic fetal liver fragments in rats. AB - The survival of allogeneic fetal liver fragments in the omentum was analyzed in rats. The lymphocyte subsets of the spleen and peripheral blood were also examined. When the fetal liver fragments were transplanted into the omentum, they survived for 2 wk, whereas adult liver fragments survived only 1 wk. In fetal liver fragments transplantation, the CD8 positive lymphocyte percentage in peripheral blood decreased significantly 3 wk after transplantation in comparison with that in adult liver fragment transplantation. The skin graft of the donor party showed a longer median survival time in rats receiving fetal liver fragment transplants than that in recipients of adult liver fragments. Although further study is needed, allogeneic fetal liver fragments survived longer in the omentum than reported elsewhere, and the decrease of CD8 positive peripheral blood lymphocytes may have been the reason for this. PMID- 7795906 TI - Comparison of different collagenases in isolation of adult pig islets. PMID- 7795907 TI - Effect of antiadhesion antibodies on pancreatic islet xenotransplantation. PMID- 7795908 TI - Role of micro-chimerism in inducing immunological tolerance by intraportal injection of donor spleen cells in rats. AB - Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) prevented liver allograft rejection. Moreover, we developed a new method using polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) analysis, and demonstrated micro-chimerism (MC) at the DNA level in the spleen 14 days after IP injection. In the present study, the long term presence of injected allogeneic SPCs was investigated at the cellular level by immunofluorescence staining as well as the DNA level using RFLP analysis. Male ACI (RT1a) rats were used as the donors and Lewis (RT1(1)) rats as the recipients. After DNA preparation from the lymphoid organs, RT1B beta domain 1 region was amplified by PCR, and RFLP analysis was performed with PvuII restriction enzyme. In the immunofluorescence staining, the monoclonal antibody, MN4-91-6, was used to detect the injected donor ACI SPCs in a frozen specimen. We did not detect MC in Lewis rats intravenously injected with 5 x 10(7) ACI SPCs on day 14. On the other hand, stable chimerism in the spleen was observed in intraportally injected rats up to 28 days after injection at not only the DNA level but also the cellular level. No chimerism was detected in other organs (including the thymus, lymph nodes, and liver). In conclusion, the long-term presence of injected allogeneic SPCs in the spleen was demonstrated after IP injection but not after IV injection, and this phenomenon may be one of the mechanisms involved in portal venous immunosuppression. PMID- 7795909 TI - T cell clonality and transplantation. PMID- 7795910 TI - Temporal pattern of synaptophysin expression in cryopreserved fetal hippocampal cells transplanted into ischemically damaged adult rat hippocampus. PMID- 7795911 TI - The challenge of individual rights. Mental health review tribunals. PMID- 7795912 TI - Categorising the behavioural toxicities of antidepressants. Proposals and requirements. PMID- 7795913 TI - Efficacy of drug treatment in obsessive-compulsive disorder. A meta-analytic review. AB - BACKGROUND: A review of the efficacy of antidepressant drug treatment in patients with obsessive-compulsive disorder (OCD), using a meta-analytic approach. METHOD: Randomised double-blind clinical trials of antidepressant drugs, carried out among patients with OCD and published in peer-reviewed journals between 1975 and May 1994, were selected together with three studies currently in press. Forty seven trials were located by searching the Medline and Excerpta Medica-Psychiatry data bases, scanning psychiatric and psychopharmacological journals, consulting recent published reviews and bibliographies, contacting pharmaceutical companies and through cross-references. Hedges' g was computed in pooled data at the conclusion of treatment under double-blind conditions or at the latest reported point of time during this treatment period. For each trial, effect sizes were computed for all available outcome measures of the following dependent variables: obsessive-compulsive symptoms considered together; obsessions; compulsions; depression; anxiety; global clinical improvement; psychosocial adjustment; and physical symptoms. RESULTS: Clomipramine was superior to placebo in reducing both obsessive-compulsive symptoms considered together (g = 1.31; 95% CI = 1.15 to 1.47) as well as obsessions (g = 0.89, 95% CI = 0.36 to 1.42) and compulsions (g = 0.79; 95% CI = 0.34 to 1.24) taken separately. Also, selective serotonin re uptake inhibitors (SSRIs) as a class were superior to placebo, weighted mean g being respectively 0.47 (95% CI = 0.33 to 0.61), 0.54 (95% CI = 0.34 to 0.74) and 0.52 (95% CI = 0.34 to 0.70) for obsessive-compulsive symptoms considered together, and obsessions and compulsions taken separately. Although on Y-BOCS the increase in improvement rate over placebo was 61.3%, 28.5%, 28.2% and 21.6% for clomipramine, fluoxetine, fluvoxamine, and sertraline respectively, the trials testing clomipramine against fluoxetine and fluvoxamine showed similar therapeutic efficacy between these drugs. Finally, both clomipramine and fluvoxamine proved superior to antidepressant drugs with no selective serotonergic properties. CONCLUSION: Antidepressant drugs are effective in the short-term treatment of patients suffering from OCD; although the increase in improvement rate over placebo was greater for clomipramine than for SSRIs, direct comparison between these drugs showed that they had similar therapeutic efficacy on obsessive-compulsive symptoms; clomipramine and fluvoxamine had greater therapeutic efficacy than antidepressant drugs with no selective serotonergic properties; concomitant high levels of depression at the outset did not seem necessary for clomipramine and for SSRIs to improve obsessive-compulsive symptoms. PMID- 7795914 TI - Cognitive therapy with obsessive-compulsive disorder. AB - BACKGROUND: People with obsessive-compulsive disorders (OCD) are widely treated with a combination of medication and behavioural techniques. The success rate is 50-85%, but both relapse and drop-out rates appear high. The use of cognitive therapy (CT) for the treatment of OCD has been suggested. The empirical evidence supporting the use of CT for OCD is examined. METHOD: A manual and computer (Medline) literature search was performed. RESULTS: Fifteen empirical studies were found: ten non-controlled, and five controlled. CONCLUSIONS: There are few controlled CT studies, and these show little evidence of improvement when CT is added to existing therapeutic techniques. PMID- 7795915 TI - One hundred cases of suicide in elderly people. AB - BACKGROUND: The White Paper The Health of the Nation targets a reduction in suicide rates. Preventive strategies must be guided by an understanding of the demography and antecedents of suicide. These issues are examined in relation to suicide by old people in Manchester. METHOD: One hundred consecutive coroners' inquisitions on people aged over 65 occurring between 1980 and 1991 in which the verdict was suicide were scrutinised and related to Health Service notes. RESULTS: Suicides were rare, numbers ranging from 0 to seven per annum per Health District. Rates did not vary between district but did within smaller sub populations. Most individuals died at home; 65% were physically ill, of whom 23% had been hospitalised within the previous year. At least 60% were clinically depressed, with 25% being prescribed antidepressants. A total of 43% had seen their general practitioner in the previous month but only 14% were in contact with psychiatric services. CONCLUSIONS: Many elderly people who commit suicide are not in close contact with primary care services; those who are may not be prescribed appropriate treatment, and few are referred for specialist care. Specialist services will fail to reduce suicide rates unless they embark upon programmes to increase public awareness of therapeutic possibilities and work more closely with primary care agencies to realise these possibilities. PMID- 7795916 TI - The limitations of official suicide statistics. AB - BACKGROUND: This study explored some of the problems associated with current procedures for the ascertainment of suicide. METHOD: A sample of 242 deaths which were known to have been self-inflicted was followed up through the coroners' courts where causes of death were legally established. RESULTS: Verdicts other than suicide were returned on half of the men, and on one-quarter of the women. CONCLUSIONS: For suicide statistics to become valid indicators of suicide rates it might be more appropriate to apply the civil, rather than the criminal, standard of proof during inquest proceedings. PMID- 7795917 TI - Anorexia nervosa. No evidence of an increase. AB - BACKGROUND: This paper examines the evidence that rates of anorexia nervosa have increased over time. METHOD: Epidemiological studies that have provided time trends in incidence rates in specific countries or psychiatric registers and prevalence surveys were reviewed to assess whether or not prevalence estimates are higher in the most recent studies. RESULTS: Estimated trends in incidence rates showed an increase but no study ruled out plausible alternative explanations. Studies showing no upward trend were as numerous and were generally based on larger samples. Analysis of 29 cross-sectional surveys conducted over the last 25 years indicated that the median prevalence rate was 1.3 per 1000 females. There was no indication that more recent surveys yielded higher prevalence rates. CONCLUSION: Anorexia nervosa remains a rare disorder and there is no evidence of a secular increase in its incidence. PMID- 7795919 TI - Towards a sociobiological model of depression. A marsupial model (Petaurus breviceps). AB - BACKGROUND: This is a sociobiological approach to depression using hierarchy and its hypothesised relevance to self-esteem in the marsupial sugar glider (Petaurus breviceps). METHOD: Differential access to resources between the dominant and submissive animal is measured by observation in four stable colonies. The dominant animals from two of these colonies are then introduced into the other two, resulting in the transferred former dominants becoming subordinate. Behavioural and biochemical measures relevant to depression and involving access to resources are then repeated. These measures include eating, drinking, social and sexual access, motility, grooming and biochemical estimates of cortisol and testosterone. RESULTS: Subordinate animals have significantly less access to resources, both in the stable colony and when the formerly dominant animals become subordinate. CONCLUSIONS: A sociobiological approach using a hierarchy model equating resource-holding potential with self-esteem, exemplified by this study, may provide new concepts and insights into the phenomenology and pathophysiology of depression. It allows comparisons to be made between animal behaviour and cognition: the lack of such has been a major difficulty in animal studies hitherto. The findings are possibly more relevant to dysthymia than to affective disorder and imply a relationship between low resource-holding potential in sub-human animals as a phylogenetic antecedent of some of the cognitive and affective aspects of depression in man. PMID- 7795918 TI - Defining subgroups of dieting disorder patients by means of the Eating Disorders Examination (EDE). AB - BACKGROUND: It is important to determine the optimal manner of categorising eating disorder patients so as to aid in the understanding of their specific psychopathological state. METHOD: We compared subgroups of eating disorder patients divided according to different sets of factors, using a structured interview which elicits the specific psychopathological features of these illnesses. The patients, comprising 116 consecutive women admitted to two university-affiliated eating disorder clinics, were grouped according to DSM-III R criteria, clinical presentation (purging, binge eating), nutritional status, and age. RESULT: The clearest separation of groups was afforded by the clinical dimension of purging as opposed to not purging. This was superior to DSM-III-R criteria. Other systems, such as presence of binge eating, and various levels of nutritional status and of age, were clearly inferior. CONCLUSION: The presence or absence of purging behaviour appears to offer the most heuristic means of categorising eating disorder patients with respect to their specific psychopathological state. PMID- 7795921 TI - Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. AB - BACKGROUND: The study tests the hypothesis that juvenile-onset schizophrenia is associated with premorbid developmental impairments. It was predicted that the pattern of developmental impairments would vary with age of onset and with gender. METHOD: A case-control design was used to examine developmental impairments in 61 consecutive juvenile-onset (age 7-17) referrals with ICD-9 schizophrenia; 61 non-psychotic psychiatric controls were matched on age and gender. Cases and controls were divided into childhood-onset (age 7-13) and adolescent-onset (age 14-17). RESULTS: The schizophrenic cases had a significantly higher risk of premorbid social (chi 2 = 9.1, P < 0.005), motor (chi 2 = 9.1, P < 0.005) and language impairments (chi 2 = 10.1, P < 0.005). Specific impairments of language production and comprehension were associated with childhood-onset schizophrenia and were independent of gender. CONCLUSIONS: Juvenile-onset schizophrenia is associated with a range of developmental antecedents. There may be a specific link between cases with a very early onset and an impairment in the processes underlying the development of language. PMID- 7795922 TI - Schizophrenic and manic brains in Nigerians. Computerised tomography findings. AB - BACKGROUND: We highlight the profile of brain computerised tomography (CT) measures among Nigerian psychiatric patients for comparison with findings from developed countries, and study of the relationship between CT values and clinical variables. METHOD: Seven brain ventricle measures of 50 schizophrenic patients, 14 manic patients, and 41 healthy control subjects were compared. RESULTS: Patients had a significantly higher mean Sylvian fissure area. The third ventricle of schizophrenic patients was significantly larger than those of control subjects. CT measures were not significantly correlated with duration of illness. CONCLUSION: The so-called functional psychotic states are most probably associated with non-specific brain abnormality. PMID- 7795920 TI - Assessment of the prevalence of psychiatric disorder in young adults. AB - BACKGROUND: The effectiveness of different assessment procedures for determining prevalence rates of psychiatric disorder in young adults was investigated. METHOD: In a two-stage multi-method procedure, the Young Adult Self-Report, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the Structured Interview for Personality Disorders (Revised), and the Global Assessment of Functioning (GAF) Scale were used to assess prevalence rates in 706 19-24-year olds from the general population. Furthermore, individuals' subjective perception of distress and referral to mental health services were assessed. RESULTS: The prevalence of any SCAN/DSM-III-R disorder was 19.3% (95% confidence interval: 11.2-27.4%). Most subjects who received a SCAN/DSM-III-R diagnosis were only mildly impaired. The highest prevalence rates of dysfunctioning (GAF score below 61) without referral to mental health services were for dissociative disorder (2.3%), sleep disorder (2.1%), alcohol dependence (1.3%) and affective disorder (1.8%). CONCLUSION: Instruments that assess functional impairment in addition to DSM-III-R diagnoses are indispensable in prevalence studies. PMID- 7795924 TI - Bereavement after homicide. A comparison of treatment seekers and refusers. AB - BACKGROUND: This brief report presents initial findings from a prospective descriptive study of adults after the homicide of a family member. Within the first year of bereavement, the responses and risk factors associated with unrecovered grief and post-traumatic stress disorder in subjects who requested or refused supportive psychotherapy were compared. METHOD: Fifty-two adult members of 237 families contacted within three months of a homicide attended a specialised out-patient clinic (32 requested, and 20 refused, supportive therapy) after a structured interview and completion of measures of grief (TRIG), trauma (RIES and DES), and death imagery. RESULTS: Only two risk factors (childhood history of sexual abuse and lack of religious faith) were associated with treatment seeking. Treatment-seeking subjects also scored significantly higher (P < 0.001) on all measures of grief, trauma, and intrusive re-enactment imagery of the dying. CONCLUSION: Adults who seek therapy after the homicide of a family member are highly reactive to all measures of trauma, grief, and death imagery. PMID- 7795923 TI - Disordered water homeostasis in schizophrenia and cerebral ventricular size. AB - BACKGROUND: A possible association between disordered water homeostasis and cerebral ventricular size in patients with schizophrenia was investigated. METHOD: In a cross-sectional study of hospitalised patients, cerebral ventricular size was measured in 16 schizophrenic patients with disordered water homeostasis and 16 matched schizophrenic controls by magnetic resonance imaging. RESULTS: Ventricle to brain ratio, third ventricular index, bicaudate index and bifrontal index tended to be greater in those with schizophrenia with disordered water homeostasis, although differences were significant only for the bifrontal index (P < 0.05). Strong negative correlations were found between ventricular size and performance on neuropsychological testing in the disordered water homeostasis group. CONCLUSION: These results provide evidence for an association between structural brain abnormality and disordered water homeostasis in a subset of schizophrenic patients. PMID- 7795925 TI - Ondansetron and opiate craving. A novel pharmacological approach to addiction. AB - BACKGROUND: Pharmacological approaches to opiate addiction have for the most part been limited to a role in detoxification. A high percentage of patients who complete detoxification programmes relapse. METHOD: In the present study, we used a simple laboratory method to investigate suggestions from preclinical studies that 5-(hydroxytryptamine) HT3 receptor antagonists have a role in the treatment of addiction. RESULTS: We showed that addicts stably maintained on methadone experienced significant craving, dysphoria, and withdrawal-like symptoms when exposed to a video containing drug-related cues. The craving was not lessened by treatment with the 5-HT3 receptor antagonist, ondansetron (4 mg orally). CONCLUSION: Our current findings do not support a role for 5-HT3 receptor agonists in the reduction of craving in opiate addicts. PMID- 7795927 TI - Psychiatric and social outcome of liver transplantation. AB - BACKGROUND: This study measures psychiatric morbidity, quality of life, and cognitive function after liver transplantation. METHOD: We undertook a cross sectional study, with a longitudinal subgroup. The setting was a tertiary referral centre for liver transplantation. The subjects were 30 post-liver transplantation patients, including 11 also interviewed before the operation. The main outcome measures were the Clinical Interview Schedule (CIS), the General Health Questionnaire (GHQ), the Nottingham Health Profile (NHP), and the Mini Mental State Examination (MMSE). RESULTS: Of the patients, 8/30 were CIS cases, and 7/30 were GHQ cases. NHP scores were higher than a previous postal study indicated, with less impairment after than before transplant. MMSE scores were 24 30. Median GHQ was 7.0 before operation and 1.0 after operation (P = 0.03), with no significant change in CIS score. CONCLUSION: Liver transplantation improves quality of life, but not to the level of the general population; post transplantation patients have a prevalence of psychiatric morbidity comparable with that of general medical patients. PMID- 7795928 TI - Post-traumatic stress disorder (PTSD) after childbirth. AB - BACKGROUND: There has been discussion about the possible occurrence of post traumatic stress disorder (PTSD) in mothers after difficult childbirth. METHOD: Four cases with a symptom profile suggestive of PTSD commencing within 48 hours of childbirth are presented. RESULTS: The PTSD was in each case associated with the delivery. In each case, there was an associated depressive illness. All four had persistent disorders, and two had difficulties with mother/infant attachment. CONCLUSION: As confirmed by other reports, the prevalence of PTSD associated with childbirth is a matter of concern. PMID- 7795926 TI - Quality of life in liaison psychiatry. A comparison of patient and clinician assessment. AB - BACKGROUND: This exploratory study investigates the performance of the Health Measurement Questionnaire (HMQ), as compared with the Psychiatric Assessment Schedule (PAS) and the Nottingham Health Profile (NHP), and compares self- and observer-completed measures. METHOD: A total of 138 medical patients scoring over the screening threshold for probable psychiatric illness completed the HMQ, NHP and PAS, and were rated by a psychiatrist on Rosser disability and distress. RESULTS: HMQ disability correlated well with NHP and PAS physical health items, while HMQ distress correlated well with the NHP emotional reactions and PAS Index of Definition. There was significant correlation between self-report and psychiatrist ratings, the latter being more sensitive to distress. CONCLUSION: The HMQ is a useful measure of generic health status in liaison psychiatry settings. PMID- 7795929 TI - Prediction of dangerous behaviour in male erotomania. AB - BACKGROUND: New cases of erotomania in men, plus cases from the literature, were analysed to explore any association between erotomania and dangerousness, and to identify possible predictors. METHOD: Files at two in-patient facilities were examined to determine the presence of DSM-III-R delusional disorder, erotomanic type. The sample (13 cases) was divided into dangerous and benign groups on the basis of serious antisocial behaviour directly related to erotomanic delusions. These cases were combined with all reports of erotomania in men (16 cases), found in the English language psychiatric literature, to allow for statistical analysis. RESULTS: Two factors, multiple delusional objects (P < 0.0005) and serious antisocial behaviour unrelated to the delusions (P < 0.05), were found to be significantly associated with dangerousness. Using a combination of these two variables it was possible to predict dangerousness with an accuracy of 88.9% (weighted prediction accuracy or 'hit rate'). We identified no false negatives but three false positives. CONCLUSIONS: The presence of multiple objects, and a history of serious antisocial behaviour unrelated to the erotomanic delusions, are useful predictors of dangerous behaviour in men with erotomania. PMID- 7795930 TI - Neuroleptic malignant syndrome. PMID- 7795931 TI - Predictors of psychiatric morbidity in cancer patients. PMID- 7795932 TI - Worcester Development Project and Powick Hospital. PMID- 7795933 TI - Effectiveness and efficiency in psychiatry. PMID- 7795934 TI - Statistical design, analysis and correspondence. PMID- 7795935 TI - Predictors of outcome in the behavioural treatment of OCD. PMID- 7795936 TI - Cognitive therapy for panic. PMID- 7795937 TI - Home-based versus in/out-patient care for people with serious mental illness. PMID- 7795938 TI - Imagery and motor processes. PMID- 7795939 TI - Use of different imagery perspectives on the learning and performance of different motor skills. AB - Two experiments are reported which examine the relative efficacy of different imagery perspectives on a slalom type and a gymnastic type task. Twenty-four able bodies sport, health and physical education students were allocated to either an internal visual imagery group or an external visual imagery group. In both experiments subjects watched video-recordings of someone completing the tasks, then performed five blocks of three trials with feedback after each block, and internal/external visual imagery before each trial. A transfer/retention trial was performed one week later. The tasks were a wheelchair slalom task and a pseudogymnastics routine performed using rhythmic gymnastics clubs to show static positions. The slalom task results suggested that in the retention test, the external visual imagery group focused on the speed of performance, whilst the internal visual imagery group focused on the accuracy of performance. These findings were interpreted as suggesting that internal visual imagery was more effective for the planning of action in response to changes in a visual field. However, in the gymnastics task, contrary to previous suggestions, external visual imagery was found to be more effective than internal visual imagery for both learning and subsequent retention. The roles of internal and external visual imagery are discussed in terms of task characteristics and the observational learning literature. PMID- 7795940 TI - Interference effects of mental imagery on a motor task. AB - It can be argued that imaginary practice and physical practice are functionally similar. Evidence in support of this hypothesis comes from several experiments demonstrating that interference effects from imaginary practice in motor learning and motor memory are similar in both direction and size to those resulting from physical practice. The purpose of the present study was to provide additional support for this finding using a retroactive interference paradigm. Sixty participants were required to practise performing a simple motor task that was to be completed in a criterion time of 700 ms. They then were randomly assigned to one of six groups. These groups differed in the amount and type of interpolated practice they experienced. One physical practice group attended one session of interpolated activity involving physical practice of another motor task. The other physical practice group participated in two such sessions. One imagery group attended a single session entailing imaginary practice of the same interpolated motor task, while the other imagery group had two such sessions. A fifth group experienced a combination of physical practice and rest periods for two interpolated sessions. A control group did not experience any interpolated activity sessions. Following the interpolated activity sessions, all groups were given a retention/reacquisition test on the original motor task. Imaginary and physical practice during the interpolated activity sessions caused similar interference effects on retention/reacquisition. All groups showed greater deviation from the criterion movement time (700 ms) during the retention test than the control group, and these deviations were in the expected direction given the nature of the interpolated motor task. PMID- 7795941 TI - On relations between perceiving, imagining and performing in the learning of cyclical movement sequences. AB - In three experiments, the effects of observational, mental and physical practice on the performance of cyclical movement sequences were investigated. Experiment 1 revealed that repeated demonstrations of the criterion motion were sufficient for adequate reproductions of the movement form and that mental or physical practice had only small additional effects. Furthermore, consistency of movement tempo and consistency of relative timing, normally seen as dependent on physical practice, were similar in all experimental conditions at the end of practice. Experiment 2 confirmed this counter-intuitive finding by demonstrating equivalent improvements in the consistency of relative timing after physical and mental practice and after practice in a perceptual discrimination task. In Expt 3, discrimination of a nonspatial version of the criterion motion from similar patterns was also found to enhance consistency, indicating that eye movements were not a crucial factor in the observed effects. The findings suggest that performance, observation and imagery of sequential patterns involve a common process, characterized as event generation, which is either coupled to an articulatory system (in the case of physical practice), synchronized with an external event (in the case of observational practice), or 'runs free' without such articulatory or perceptual coupling in the case of imagery. PMID- 7795942 TI - Representation and performance: reproduction of form and quality of movement in dance by eight- and 11-year-old novices. AB - This study examined the effects of age on the cognitive representations in modelling. A total of 48 eight- and 11-year-olds were asked to watch a dancer performing a ballet sequence of three steps in order to reproduce it. They were able to see the film as many times as they wanted. All subjects were novices to dance. Both quantitative (number of observations required to learn the sequence, number of steps executed) and qualitative (form and quality of the performance) factors were assessed. The results indicated an effect of age on the number of requested observations and on the number of subjects able to perform the entire movement series. The mean form scores did not differ significantly between the two groups, but the mean quality score was higher for the 11-year-olds. We also noted a great heterogeneity in the performances. The results are discussed in terms of the role of cognitive and motor factors in observational learning by age and of the possibilities that cognitive representations offer for coding the different properties of movement. PMID- 7795943 TI - Visual imagery and enactment of actions in memory. AB - It was assumed that self-performing an action necessarily focuses information processing on action-relevant information in order to guarantee smooth enactment. As a consequence, enacting an action should provide the subjects with excellent item-specific information and hinder the subjects from encoding contextual information that is not a part of the action proper. These hypotheses were tested in paired-associate learning experiments in which unrelated action-verb-pairs served as stimuli. Free recall (FR) of the action verbs was considered to indicate item-specific encoding, and cued recall (CR)--with one element of a pair serving as a cue for the other--to reflect context encoding. The verb-pairs were learned essentially under four types of instructions: under standard learning instructions (as a control), under enactment instructions, under self-imagery instructions, and under other-imagery instructions. The results demonstrated that enactment led to better FR than standard learning and the two imagery conditions, showing that enactment provides excellent item-specific information. CR was equally poor after overt enactment and self-imagined performance and worse after standard learning and after imagining somebody else performing an action, showing that motor encoding hinders pair integration--i.e. efficient context encoding. PMID- 7795944 TI - Visuospatial working memory, movement control and executive demands. AB - Developments in the concept of a specialist visuospatial resource in working memory owe much to a pair of tasks originally developed by Brooks (1967), involving respectively the generation and retention of a mental image of a matrix pattern and the retention of a verbal sequence. Previous literature has demonstrated that the matrix task calls on cognitive resources which are involved in both the processing of visual input and the generation of movement sequences. Using dual task methodology, the study reported here demonstrates that the matrix and verbal versions of the task do indeed rely on separate, specialized cognitive resources, one of which is also involved in generation of action. However, when the secondary task (random generation of numbers) was very demanding of general purpose cognitive resources both the matrix and verbal tasks were performed poorly, suggesting that each of these tasks draw heavily on a common, general purpose resource as well as on their respective specialist resources. It is argued that random generation offers a means to assess general purpose cognitive resources and that the cognitive processes involved in the Brooks tasks may be more complex than has been previously assumed. PMID- 7795946 TI - Psychophysiological correlates of dynamic imagery. AB - Brain Electrical Activity Maps were recorded from 20 subjects whilst performing: (a) the Vandenberg & Kuse Mental Rotation Test (MRT) and: (b) the Isaac, Marks & Russell Vividness of Movement Imagery Questionnaire (VMIQ), and under control conditions. Subjects were classified as good or poor imagers, first on the basis of their VMIQ scores, and secondly on their MRT scores. Alpha, beta 1 and beta 2 at different cortical regions were compared between groups and between task performance and control conditions. During MRT significant reductions in alpha amplitude were found over both right and left parietal areas and over the left frontal region. In beta 1 non-significant trends in the same direction were observed in the same regions found to be significant in alpha. Non-significant trends in beta 2 were observed over the right parietal and frontal regions. No differences in amplitude at any frequency band were found between good and poor VMIQ scorers but subjects with high MRT scores showed greater alpha amplitude at many sites in the parietal, parieto-occipital and frontal areas than subjects with low MRT scores. During VMIQ testing the VMIQ high imagers showed a non significant trend towards higher alpha amplitude at frontal regions and some scattered parietal and occipital sites and significantly higher levels of beta 2 in the left frontal region. However, no differences were found between imagery and control conditions. The results confirm the involvement of motor as well as spatial processes in dynamic imagery. PMID- 7795945 TI - Topographical distribution of EEG activity accompanying visual and motor imagery in vivid and non-vivid imagers. AB - Brain mapping techniques were used to investigate the topographical distribution of electroencephalographic (EEG) activity accompanying visual and motor imagery in four different tasks. Participants were selected for their self-reported vivid or non-vivid imagery using the Vividness of Visual Imagery Questionnaire (VVIQ) and the Vividness of Movement Imagery Questionnaire (VMIQ). Topographical maps of EEG activation revealed that alpha power was attenuated in vivid images during visual imagery, particularly in the left posterior quadrant of the cortex, but enhanced during motor imagery. The imagery vividness variable interacted with experimental condition or with experimental condition and location in all four tasks. Because demand characteristics and instrument artifacts can be eliminated as possible explanations of the results, these data provide strong evidence of the construct validity of the VVIQ and VMIQ as measures of visual and motor imagery experience. PMID- 7795947 TI - Global and multidimensional self-concept as a predictor of health practices in middle adolescents. AB - OBJECTIVE: To describe the relationship between global and multidimensional aspects of self-concept and the health practices of adolescents. METHODS: A total of 195 adolescents, ages 14-17, who attended two Senior high schools within rural county in a Southeastern state completed research questionnaires. RESULTS: The adolescents in this sample scored average or slightly above average for global self-concept on the Piers-Harris Self-Concept Scale. Adolescents scored lowest in the health-related behavior of time spent eating a balanced diet and highest in the area of safety. The single highest correlation between self-concept and self care practices was between the total health practice score and global self concept. CONCLUSIONS: The results suggest that an individual's knowledge, feelings of worth related to status at school, and level of anxiety and stress are important predictors of health behavior. PMID- 7795948 TI - Understanding separation anxiety disorder. AB - BACKGROUND: When children are acutely ill and life is threatened, separation anxiety can develop in parents and children. Separation anxiety has been studied through two traditions--as a normative phenomenon and as a disorder. SOURCE: A comprehensive review of the literature. OBJECTIVE: To analyze and evaluate the literature to derive clinical and research implications. CONCLUSIONS: Support was found for the development of interventions beyond the developmental stage of early childhood. The need for a family approach was evident. PMID- 7795949 TI - For want of a nail, the kingdom was lost. PMID- 7795951 TI - Sadistic statistics. PMID- 7795950 TI - Reflection on children and families in bipartisan politics. PMID- 7795952 TI - Clomipramine and obsessive-compulsive disorder. AB - Clomipramine is a tricyclic antidepressant that was the first effective agent in the treatment of OCD. Its capacity to block serotonin reuptake appears to be essential to reducing the primary symptoms of OCD. Like other tricyclic agents, CMI has an array of possible side effects including gastrointestinal, autonomic, hepatic, and cardiac problems that need to be considered in the clinical management of children and adolescents treated with CMI. Evaluation of clinical response begins with the identification of target symptoms and monitoring the change in these target symptoms over time. This effort can be aided by the use of clinical rating instruments such as the Children's Yale-Brown Obsessive Compulsive Scales and, to a limited degree, drug plasma levels. Although many OCD patients manifest a positive response to CMI, some patients do not. This variation suggests that other neurochemical systems may be implicated in OCD. PMID- 7795953 TI - An interview with Kathleen Scharer, MS, RN, CS, FAAN. Interview by Linda M. Fink. PMID- 7795954 TI - It's clear: seclusion is controversial. PMID- 7795955 TI - Child bereavement after paternal suicide. AB - BACKGROUND: Studies of child suicide survivors are rare and often these studies have not included direct interviews with children. OBJECTIVES: To describe the bereavement process in a sample of prepubertal children whose fathers died by suicide within the previous three years. METHODS: Sixteen prepubertal children, their mothers, and a relative or caretaker were interviewed to examine grief, trauma, and behavior within 25 months of paternal suicide. RESULTS: Reminiscing was the most frequently endorsed grief behavior. Males were more likely than females to score above the standard means for CBCL scores. PTSD scores were significantly related to parental threats of divorce and exposure to death by discovery of the body. CONCLUSIONS: The concept of grief and trauma as separate and overlapping phenomena is supported by the study findings. PMID- 7795957 TI - Appropriateness of medical care in Europe: a commentary. PMID- 7795956 TI - Concerted action programme on quality assurance in hospitals 1990-1993 (COMAC/HSR/QA). Global results of the evaluation. AB - This article describes the global results of the evaluation of a concerted action programme on quality assurance in hospitals that was executed between 1990 and 1993 in a total of 262 hospitals in 15 European countries. The programme aimed to introduce quality assurance notions into European hospitals and focused on four specific topics; record keeping, prophylactic antibiotic use in surgery, preoperative assessment and the prevention of bedsores. Evaluation took place on a national level (descriptive country reports), hospital level (questionnaire) and topic level (questionnaire and results of QA studies performed in the participating hospitals). Different situational and operational factors on national, hospital and topic level, that seem to influence the effectiveness of strategies for the implementation of quality assurance, are identified. The relative importance of these factors is discussed and supported with empirical evidence. Part of the analysis is based on quantitative data based on comparing the situation in 113 hospitals in 1990 and 1993, before and after the intervention. PMID- 7795959 TI - Should we assess appropriateness of care in Europe? PMID- 7795958 TI - Variation in use of breast surgery and characteristics of hospitals' surgical staff. AB - OBJECTIVE: To assess whether and how the characteristics of hospitals' surgical staff can predict utilization of breast conserving surgery. We anticipated that the use of the procedure was more frequent in hospitals with a greater proportion of younger and female surgeons on their staff. SETTING: Sixty-two hospitals with different level of organization for the care of cancer patient from eight Italian regions were included. DESIGN: We collected information on the personal characteristics (age and sex) of all surgeons on the staff of the participating centers. A concurrent pattern of care study was undertaken, in order to assess the utilization of breast conserving procedures. RESULTS: The use of conservative surgery was 16%, 20%, 31%, in centers with 0%, < 20% and 20-50% female surgeons respectively (p = 0.003), while no associations emerged between the mean age of the surgical staff and the use of conservative surgery. This relationship also held true after adjusting for other patients' characteristics, such as stage of disease, age and presence of comorbidity. However, overall the use of patient related and staff-related characteristics to predict the number of breast conserving surgeries performed in each area was able to explain only 16% of the observed variability in the use of breast conserving surgery. CONCLUSIONS: Even though in this study a large proportion of the observed variation in the use of breast conserving surgery was still left unexplained, this finding suggests that assessing the relationship between doctors' characteristics and the use of scientific evidence is an important topic for health service research and can be of some help in exploring variations in clinical practice styles. PMID- 7795960 TI - The appropriateness of performing coronary angiography in two major teaching hospitals in Israel. AB - OBJECTIVE: To assess the appropriateness of using coronary angiography in two major medical centers in Israel. METHODS: (a) Development of dichotomous appropriateness rating by concensus of an expert panel for possible indications to use coronary angiography; (b) applying the panel's rating to clinical data gathered from interviews and records of 499 patients who underwent coronary angiography. RESULTS: Angiographies were performed inappropriately in 58% of patients: in 56% neither prognostic stratification was performed, nor was comprehensive medical therapy prior to angiography undertaken. Referral to catheterization from an acute care hospital, compared to ambulatory referral, correlated independently with an inappropriate angiogram. CONCLUSION: In the Israeli public health system there is still a high rate of inappropriate coronary angiography, most of the cases being due to error in management before performing angiographies. PMID- 7795961 TI - Effect of panel composition on appropriateness ratings. AB - Cholecystectomy is performed frequently and for relatively few indications. An all surgical panel agreed on more indications and fewer contra-indications for cholecystectomy than a mixed specialty panel but did not approve indications for patients with higher comorbidity. In mixed panels subspecialists (gastroenterologists) were more conservative than generalists and surgeons. Similar findings have been shown for carotid endarterectomy. Comparing the results of British and Israeli panels showed variations in rating appropriateness that indicate differences in approach between countries. We conclude that the composition of panels will influence the assessment of appropriateness. PMID- 7795962 TI - Implementing guidelines in general practice. Evaluation of process and outcome of care in chronic diseases. AB - In a prospective longitudinal study over 21 months the performance of general practitioners and the disease status of their patients was measured during the formulation and implementation of guidelines on follow-up care. Data on 15 general practitioners and on 613 patients with hypertension, 95 with diabetes mellitus, 66 with chronic ischemic heart disease, 115 with chronic respiratory disease, and 17 with osteoarthritis were used for analysis. Performance measures were defined and for each disease a disease status indicator was used. The possibly modifying effect of compliance of the general practitioner, and of patient compliance with the guidelines was taken into account. The general practitioners formulated consensus guidelines on follow-up care and implemented these guidelines in their practices. The implementation was supported by peer review. The performance of general practitioners tended to conform more with the guidelines during the study period, especially with regards to actions that should be performed routinely. There were no major changes in the disease status indicators. Compliant hypertensive patients had a normotensive status more frequently than non-compliant patients. Diabetic patients were more likely to be normoglycaemic when they received care according to guidelines. None of the differences were statistically significant over time. PMID- 7795963 TI - Measuring unmet needs to assess the quality of home health care. AB - Until now home care research has been primarily focused on functional limitations. The instrument presented in this article also takes into account needs for psychosocial care, extra information, nursing care, and extra arrangements such as adaptations of the house. Elderly people with a chronic disease (n = 311) were interviewed using structured questions concerning the presence of unmet needs. The six need scales represented two dimensions: needs referring to physical functioning and needs referring to psychosocial well-being. However, considerable differences were found in the amount of formal and informal care and in the presence of unmet needs between the need scales constituting one dimension. Indications for construct validity were found for five out of six need categories. The results show that, when evaluating home health care, the full range of needs has to be considered and the presence of unmet needs can be used as an indicator of the quality of home health care. PMID- 7795964 TI - Data quality in a DRG-based information system. AB - The aim of this study initiated in May 1990 was to evaluate the quality of the medical data collected from the main hospital of the "Hospices Civils de Lyon", Edouard Herriot Hospital. We studied a random sample of 593 discharge abstracts from 12 wards of the hospital. Quality control was performed by checking multi hospitalized patients' personal data, checking that each discharge abstract was exhaustive, examining the quality of abstracting, studying diagnoses and medical procedures coding, and checking data entry. Assessment of personal data showed a 4.4% error rate. It was mainly accounted for by spelling mistakes in surnames and first names, and mistakes in dates of birth. The quality of a discharge abstract was estimated according to the two purposes of the medical information system: description of hospital morbidity per patient and Diagnosis Related Group's case mix. Error rates in discharge abstracts were expressed in two ways: an overall rate for errors of concordance between Discharge Abstracts and Medical Records, and a specific rate for errors modifying classification in Diagnosis Related Groups (DRG). For abstracting medical information, these error rates were 11.5% (SE +/- 2.2) and 7.5% (SE +/- 1.9) respectively. For coding diagnoses and procedures, they were 11.4% (SE +/- 1.5) and 1.3% (SE +/- 0.5) respectively. For data entry on the computerized data base, the error rate was 2% (SE +/- 0.5) and 0.2% (SE +/- 0.05). Quality control must be performed regularly because it demonstrates the degree of participation from health care teams and the coherence of the database.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7795965 TI - Quality in alternative medicine--a rejoinder. PMID- 7795966 TI - A dosage system for gamma ray therapy. 1934. PMID- 7795967 TI - Magnetic resonance imaging of endocrine tumours of the pancreas. AB - Seven patients who had functioning or non-functioning endocrine pancreatic tumours were investigated by magnetic resonance imaging. Combinations of fat suppressed T1 weighted spin echo and gradient recalled echo (n = 7), T2 weighted spin echo (n = 3) and gadolinium diethylamine triamine pentaacetic acid (Gd-DTPA) enhanced fat suppressed T1 images were acquired. Magnetic resonance imaging detected five of seven tumours prospectively (three of which were smaller than 10 mm) and a further 10 mm tumour retrospectively. Tumours were low signal on T1 weighted images and showed enhancement after Gd-DTPA. On T2 weighted images one tumour was hyperintense, and two were isointense with normal pancreas. Computed tomography, transabdominal ultrasound and angiography were performed in six patients but detected only one tumour each. Intraoperative palpation and ultrasound detected all tumours. If pre-operative imaging is required magnetic resonance imaging is the technique of choice to detect small endocrine pancreatic tumours. PMID- 7795968 TI - Mediastinal lymph node size in an Asian population. AB - There is a high incidence of respiratory tuberculosis in the British population of Indian subcontinent (Asian) ethnic origin. Granulomatous diseases can cause long term lymph node enlargement. Separate computed tomography (CT) criteria for normal nodal size could therefore be necessary when staging thoracic malignancy in Asian patients. The objective of this study was to measure mediastinal lymph node size in an Asian population, and to correlate nodal size with previous tuberculosis. Chest CT scans on all Asian patients over a 5 year period were reviewed and those with pulmonary disease, malignancy or grossly distorted anatomy were excluded. The study group consisted of 48 patients (26 male, 22 female) aged 10-75 years (mean 47 years). All nodes were measured and the site of those greater than 7 mm was recorded using the American Thoracic Society (ATS) lymph node map. 81.3% of patients had nodes less than or equal to 7 mm at all ATS stations, 10.4% had nodes of 8-10 mm and 8.3% had nodes greater than 10 mm. All nodes measuring more than 7 mm were in regions 4R, 10R and 7. Fourteen patients had signs of previous tuberculosis, and in this group 50% had nodes greater than 7 mm as compared with 6% in the group with no signs of previous tuberculosis (p < 0.001, X2 test). Despite these differences only four of the 48 patients (8.3%) had nodes greater than 10 mm, which is in keeping with other general population studies. Thus the generally accepted size criteria for mediastinal lymph node enlargement (greater than 10 mm) can reasonably be applied to all Asian patients when staging lymphoma or bronchogenic carcinoma. PMID- 7795969 TI - Two-dimensional time-of-flight magnetic resonance angiography in the coronal plane for abdominal disease: its usefulness and comparison with conventional angiography. AB - Using two-dimensional time-of-flight magnetic resonance angiography (2D-TOF MRA) in the coronal plane, 54 cases of arterial disease and 46 cases of venous disease were evaluated. The results were compared with those of conventional angiography to establish their relative usefulness for diagnosing abdominal diseases. Using 2D-TOF MRA, relatively large vessels such as the splenic artery, the trunks of the superior mesenteric artery (SMA) and the renal artery were clearly visualized. However, smaller vessels such as the gastroduodenal artery, main hepatic artery, branches of the SMA and the renal artery were not clearly imaged. The diameters of stenotic arteries correlated well with their images on conventional angiography (r = 0.953). In the venous system, the splenic, renal and portal veins and the first branches of the portal vein bilaterally were clearly imaged. Veins, normal or abnormal, less that 5 mm in diameter were not clearly imaged using 2D-TOF MRA. 2D-TOF MRA in the coronal plane provided useful diagnostic information, especially regarding venous diseases, tumour thrombi in the portal vein, renal vein or inferior vena cava (IVC), collateral vessels or shunts, vascular malformations, and the relationships between the portal and hepatic veins. Limitations encountered in arterial disease did not interfere with evaluations of venous disease. PMID- 7795970 TI - Audit of the value of double reading magnetic resonance imaging films. AB - 100 consecutive magnetic resonance imaging (MRI) examinations were reviewed independently by two radiologists. Patients were selected so that the anatomical areas of clinical interest coincided with the special interests of the reviewers. The reviewers were both consultant radiologists, one with 3 years' and the other with 6 years' experience of MRI. Hard copy images from the MRI examinations were reported independently by both reviewers. Of the 100 MRI examinations, there was full concordance of opinion in 61/100. Of the remaining 39 cases, four (10%) were considered "minor unrelated" differences, 12 (31%) "minor related" differences and 23 (59%) "major related" differences resulting in a significant change in patient management. PMID- 7795971 TI - The diagnostic implication of falcine calcification on plain skull radiographs of patients with basal cell naevus syndrome and the incidence of falcine calcification in their relatives and two control groups. AB - The purpose of our study was to identify the incidence of falcine calcification shown on plain skull radiographs in people with basal cell naevus syndrome (BCNS) and in their relatives compared with a normal population. A population of people with BCNS and their relatives was identified on non-radiological grounds and the incidence of falcine calcification on skull radiographs in each of these two groups was compared with the incidence of falcine calcification in a control group of people and of a larger group who attended casualty departments. Falcine calcification was graded into dense, fine but definite, and faint. 85 people with BCNS had nearly 100% incidence of falcine calcification in adults. 83 first degree unaffected relatives showed no excess over "normal" incidence of falcine calcification. In the 970 casualty patients some falcine calcification was common (> 20%) in males over 30 and in females over 50 years of age. It occurred earlier and was more common in males than in females. Dense calcification occurred in 5 7% of females and males over 60 years of age. Dense calcification was rare (< 2%) under the age of 40 years. In conclusion, falcine calcification should be regarded as the fourth major feature and a very important diagnostic feature of BCNS. An adult labelled as a BCNS sufferer without falcine calcification probably has not got the syndrome. The genetic defect responsible for the metabolic defect resulting in dural calcification is probably the same as, or in close linkage disequilibrium to, that responsible for the major clinical features of the syndrome. The age and sex distribution of falcine calcification in a general hospital casualty population is described. PMID- 7795972 TI - Functional magnetic resonance imaging at 1 T: motor cortex, supplementary motor area and visual cortex activation. AB - Functional activation of the brain has been visualized using magnetic resonance imaging (MRI). Early studies used echo planar imaging and magnetic fields of 2 T and above. However, recent studies have successfully shown the activation of visual and motor areas of the brain using conventional clinical 1.5 T MRI systems. The purpose of the present study was to replicate these studies at a lower field strength. Eight motor and two visual activation studies were performed using a 1 T clinical scanner. Activation was seen in the contralateral motor cortex during motor stimulation in six of the eight volunteers. Activation was also documented within the contralateral supplementary motor area in four of the six volunteers with motor cortex activation. The supplementary motor area was located in the posteromedial aspect of the superior frontal gyrus. Both volunteers subjected to photic stimulation showed activation within the visual cortex. Results show that functional imaging can be successfully carried out with a 1 T clinical scanner. The size of the image intensity on activation change suggests that contrast may not be due solely to susceptibility changes. PMID- 7795973 TI - Clinical amplitude/velocity reconstructive imaging (CARI)--a new sonographic method for detecting breast lesions. AB - X-ray mammography and breast ultrasound are methods for the detection of breast lesions, especially cancers. They work in a complementary manner, but only X-ray mammography can be used for screening purposes because the recent sonographic techniques are not as cost-effective, not as fast as mammography, observer dependent and, in some instances, not reliable enough. A new ultrasound method is described which uses an X-ray-identical examination set-up and the following two properties of breast lesions: change of echo patterns behind the lesion and increased sound velocity, especially within malignant lesions. These features can be imaged on a reference structure, a reflecting plate positioned on the side of the breast which is opposite to the transducer. Results of pre-operative examinations of 80 patients with 39 benign and 52 malignant lesions are reported. Clinical, histopathological, and especially X-ray mammography findings are compared. Five cancers were not detectable by ultrasound but had clear suspicious signs on X-ray mammography. Nine cancers were not detected by X-ray mammography but were clearly visible with the new sonographic examination. By the combination of X-ray mammographic findings and their behaviour with the new sonographic method some lesions could correctly be identified as benign. The new sonographic method works in a complementary way to X-ray mammography. By further technical development it could be automated and probably performed as easily, as fast and as reproducibly as X-ray mammography. Using this method systematically in combination with X-ray mammography the detection rate of breast cancer could possibly be increased and unnecessary biopsies of benign lesions could be prevented. PMID- 7795974 TI - Selection of appropriate ultrasound methods for the estimation of fetal weight. AB - Many methods for fetal weight estimation have been proposed. Earlier formulae were derived solely by regression analysis but more recently formulae based on physical models have been developed. Some of these formulae are lengthy and difficult to use. The main purpose of this study was to evaluate a concise area based formula developed several years ago against popular and recently published formulae. Data from 388 patients over a 5 year period were collected from clinically required ultrasound scans performed within 10 days of delivery. Four of the seven formulae evaluated proved to be equally accurate over a broad range of birthweights (mean absolute deviations 245-249 g), including the area based formula and a circumference based formula derived from it. On the grounds of the number of terms, the precision of coefficients, the physical meaning and the greater accuracy of individual area measurements compared with those derived from circumference, the area based formula should be the method of choice. PMID- 7795975 TI - A population study of the screening potential of assessment of trabecular pattern of the femoral neck (Singh index): the Chingford Study. AB - The trabecular pattern of the femoral neck (Singh index) has been used as a measure of osteopenia and fracture risk but the value of this method is controversial. This study assessed the usefulness of the Singh index (SI) by using dual energy X-ray absorptiometry (DXA) as the "gold standard". 659 Caucasian women (45-70 years) from an age-sex register of a general practice had their femoral neck and lumbar spine bone densities measured by DXA and had antero posterior hip X-rays performed which were then categorized into six osteopenia grades using the SI method. The intraobserver and interobserver reproducibility of this method was good (kappa = 0.64 and 0.61, respectively). The SI grades correlated significantly with body mass index (r = 0.35) and age (r = 0.17) (p < 0.001). The mean femoral neck and lumbar spine bone densities were significantly higher with increasing SI grade even after adjustment for age and body mass index (p < 0.001). The proportion of subjects below the fracture threshold (2 SD below mean peak bone mass) decreased with increasing SI grade, ranging from 100% in SI grade 2 to 16.8% in SI grade 6. There was, however, wide overlap of bone densities between the grades. Using the criteria "osteoporosis < or = SI grade 4", the sensitivity and specificity of the SI method diagnosing low bone mass was 35.1% and 90.0%, respectively. These data suggest that the SI is a reproducible tool which may detect differences in bone mass between populations or subgroups within populations, although caution should be used in classifying individual patients because of the wide variation in bone density. The method has a low sensitivity but a relatively high specificity in diagnosing low bone mass. PMID- 7795976 TI - A method for estimating compressed breast thickness during mammography. AB - Measurements of compressed breast thickness during mammography is necessary for the calculation of breast dose. In theory, it should be possible to calculate breast thickness from the separation of images of radio-opaque markers attached to the compression paddle. Such a technique has been evaluated on two models of X ray set using simulated and real breasts. The results show that breast thickness at a given position can be determined with an average error of about 2 mm by this method, which is likely to be adequate for dosimetry. PMID- 7795977 TI - Radiotherapy for stages I and II testicular seminoma: results and morbidity in 238 patients. AB - We have undertaken a retrospective analysis of 238 patients with Stages I and II seminoma of the testis treated with radiotherapy in Edinburgh between 1974 and 1989. There were five deaths from seminoma. Cause-specific survival for the whole group at 2 and 5 years was 99.2% and 98.1%, respectively. Cause-specific survival at 2 and 5 years by stage (Royal Marsden staging classification) was: Stage I, 99.5% and 98.7% and Stage II, 98.1% and 96.1%. Fourteen (5.9%) patients relapsed (one after treatment for his second testicular seminoma). Eight were given successful salvage treatment, five died of seminoma and one died of intercurrent disease. 13 (5.5%) patients developed World Health Organisation (WHO) grade 3 gastrointestinal or haematological toxicity and two developed grade 4 gastrointestinal toxicity as a result of abdominal radiotherapy. 22 patients (9.2%) developed problems ascribed to late morbidity of abdominal radiotherapy including 18 with peptic ulcer disease. Contralateral testicular tumours occurred in seven (2.9%) patients and five (2.1%) patients developed malignancies at other sites. PMID- 7795978 TI - A comparison of the effects of methotrexate and misonidazole on the germinal cells of the subependymal plate of the rat. AB - The cytotoxic effects of the drugs methotrexate (MTX) and misonidazole have been assessed in the rat brain by quantifying changes in the constituent cell populations of a glial cell progenitor layer, the subependymal plate (SEP). Three distinct cell types can be identified in the SEP on the basis of their nuclear morphology: cells with small dark (SD), small light (SL) or large light (LL) nuclei. The cells with SD nuclei may present pluripotential glial cell precursors. A reduction in the total nuclear density of the SEP, after the local ventricular administration of MTX, could be accounted for largely by a loss of cells with SD nuclei; to approximately 45% of control values 2 days after MTX followed by a full recovery in numbers by day 5. A further decline in the number of cells with SD nuclei occurred at 12 weeks after MTX administration. The pattern of changes in the cellularity of the SEP, after misonidazole administration, were similar to those observed after MTX treatment, although the magnitude of the response was reduced. It was concluded that both drugs, but MTX in particular, could have a potential additive effect on glial progenitor cells when used in combination with other forms of cancer therapy including radiation. PMID- 7795980 TI - Case report: pseudotumoral pelvic retroperitoneal fibrosis associated with orbital fibrosis. AB - We report the case of a man with bilateral orbital fibrous pseudotumours and a large pelvic mass which was initially thought to be malignant. Sonographically guided transrectal core biopsies showed it to be a fibrotic retroperitoneal pseudotumour. The mass decreased after steroid therapy. The computed tomography and magnetic resonance imaging features of this unusual form of pelvic fibrosis as well as the association with heterotopic fibrosis are discussed. PMID- 7795979 TI - Technical note: multimedia clinical records: results of a pilot project at the Radiation Therapy Department of Florence. AB - A system based on Macintosh, Hypercard and a local network was developed at the University and Hospital Department of Radiation Therapy, Florence, Italy, to manage the clinical records as a complex data structure (data, texts, drawings and image storage and retrieval). After 4 years, the system produces over 2000 new charts a year and manages more than 15,000 clinical records. Electronic records are produced, printed and updated in their traditional form to be put on file in our archive. On-line consultation of the clinical records is possible from every workstation of the structure even as it is producing, updating, or printing a chart. Physicians and clinical clerks, with different access privileges, currently use the system for all these purposes. The clinical records are typed by secretaries who receive dictation on microcassettes. No extra staff were necessary to set up and manage the system and training was simple. The new system changed neither the organization and structure of the traditional records, nor the flux of information; new tools (computers, printers and a network) were introduced to manage the information and the charts. The author describes the aims of the original project and the results. PMID- 7795981 TI - Case report: sixth nerve palsy following radiculography. AB - Complications following myelography do not usually cause serious disability. However, we report a case of sixth nerve palsy where the disability lasted a few months. We also discuss the possible pathogeneses. PMID- 7795982 TI - Case report: simulated thoracic aortic dissection on magnetic resonance in a patient with interruption of the inferior vena cava. PMID- 7795984 TI - Case report: therapeutic transcatheter embolotherapy in the control of recurrent haemorrhage from lymphoma of the small bowel. AB - Lymphoma is one of the commonest primary malignancies of the small bowel. Gastrointestinal tract haemorrhage is a relatively infrequent presenting feature or complication. We describe the use of repeated transcatheter embolization as the primary treatment in the control of recurrent haemorrhage from the small bowel in a patient with B-cell lymphoma. Few cases of transcatheter embolotherapy have been described in such situations. This form of treatment is a therapeutic option in those unfit for transcatheter vasoconstrictor infusion or surgery. PMID- 7795983 TI - Case report: intraventricular meningioma with cerebellopontine angle and drop metastases. AB - A 34-year-old Chinese woman underwent successful gross total excision of a benign fibroblastic meningioma, pre-operatively diagnosed by computed tomography (CT), arising from the left lateral ventricle of the brain. After a quiescent period of 5 years, CT and magnetic resonance imaging (MRI) demonstrated tumour recurrence at the same site. Despite two further excisions of progressively malignant intraventricular meningiomas and treatment with radiotherapy, the patient rapidly developed bilateral cerebellopontine angle and spinal drop metastases. CT and MRI were useful in demonstrating the location and extent of recurrent intraventricular meningiomas, as well as metastatic spread via the cerebrospinal fluid. PMID- 7795985 TI - Case of the month: all's well that ends well (with apology to W Shakespeare). PMID- 7795986 TI - Technetium-99m HMPAO labelled leucocyte scanning in the initial diagnosis of Crohn's disease. PMID- 7795987 TI - Comparison of conventional Lewis-Tanner two-stage oesophagectomy with the synchronous two-team approach. AB - Twenty-seven patients with oesophageal carcinoma had subtotal oesophagectomy by the Lewis-Tanner operation (group 1, n = 14) or a synchronous modification (group 2, n = 13). Synchronous operations were completed more quickly (230 versus 305 min, P < 0.01), but with more time spent under single-lung anaesthesia (160 versus 120 min, P < 0.01) and a greater fall in systolic blood pressure during hiatal manipulation (60 versus 30 mmHg, P < 0.01). Operative blood loss was not significantly greater in group 2, but the total volume of blood transfused in the peri-operative period was greater in this group (5 versus 3 units, P < 0.01). Four patients in group 1 suffered significant postoperative complications, compared with seven in group 2; three postoperative deaths occurred in group 2. This study suggests that the synchronous two-team oesophagectomy produces a higher incidence of complications than the conventional operation. Continued use of the Lewis-Tanner two-stage oesophagectomy is recommended for patients with carcinoma of the oesophagus. PMID- 7795988 TI - Endovascular repair of aortic aneurysm. PMID- 7795990 TI - Port site metastases after laparoscopic colorectal surgery for cure of malignancy. AB - Laparoscopic surgery is excellent for treating benign disease of the colon and rectum, and for palliative operations for malignancy. Its application for cure of colorectal malignancy, however, must be approached with caution. Port site recurrence of tumour is a particular, and increasingly recognized, drawback. This review discusses the evidence to date to support prospective randomized trials of laparoscopic colectomy for cure of carcinoma. PMID- 7795989 TI - Postoperative pain relief. PMID- 7795991 TI - Neoplastic lesions of the appendix. AB - Neoplasms occur in 0.5 per cent of appendices. Ultrasonography or computed tomography is beneficial, but preoperative detection is rare. At operation, the diagnosis is considered in under half of cases. Mucocele, localized pseudomyxoma peritonei, benign tumours and most appendiceal carcinoids are cured by appendicectomy alone. Right hemicolectomy is indicated for: (1) invasive adenocarcinoma; (2) tumours close to the caecum; (3) lesions larger than 2 cm; (4) mucin production; (5) invasion of the lymphatics, serosa or mesoappendix; and (6) cellular pleomorphism with a high mitotic rate. Tumours of 1-2 cm, small mucinous carcinoids, adenocarcinoma confined to the mucosa, and tumours in children may be treated by appendicectomy alone at the surgeon's discretion. The 5-year survival rate associated with classical carcinoid is more than 90 per cent. The prognosis of mucinous carcinoid is intermediate between that of classical carcinoid and well differentiated adenocarcinoma. The prognosis of adenocarcinoma is determined by Dukes' stage and is similar, stage for stage, to that of colorectal carcinoma. PMID- 7795993 TI - Proctographic changes after rectopexy for solitary rectal ulcer syndrome and preoperative predictive factors for a successful outcome. AB - Rectopexy is advocated as treatment for solitary rectal ulcer syndrome despite variable outcome. Sixteen patients with this condition, who remained symptomatic after surgery, were examined before and after operation by evacuation proctography and compared with a matched group of seven patients whose symptoms had been relieved, to investigate the effect of rectopexy on rectal configuration or emptying, or both, and to identify any preoperative factor associated with a good outcome. Rectal prolapse, demonstrated in 19 of 23 patients before operation (internal in 12, external in seven), was seen in only one patient after surgery. The rectal axis became more vertical at rest (median 44 degrees before operation versus 35 degrees after surgery, P = 0.006) and on evacuation (median 38 degrees versus 31 degrees, P = 0.023). Preoperative evacuation time was increased in patients with poor outcome (median (range) 22 (8-60)s versus 10 (5-15)s, P = 0.008). Rectopexy successfully treats rectal prolapse in patients with solitary rectal ulcer syndrome and alters rectal configuration. These features, however, are unrelated to outcome. Prolonged preoperative evacuation time, suggesting a defaecatory disorder, may predict poor symptomatic outcome. PMID- 7795992 TI - Bile duct injury and bile leakage in laparoscopic cholecystectomy. AB - The introduction of laparoscopic cholecystectomy has been associated with an increased incidence of bile duct injury. This review presents the incidence of bile duct injury in reported series and examines the role of the learning curve and other contributing factors. There is good evidence to suggest that, with adequate training and experience, the incidence of biliary injury can be reduced to a level comparable to that of open cholecystectomy. Continued audit is required to ensure that the low complication rates achieved in selected centres with wide experience are reproduced by the surgical community in general. PMID- 7795994 TI - Faecal occult blood testing and colonoscopy in the surveillance of subjects at high risk of colorectal neoplasia. AB - Colonoscopy is the established method of surveillance of subjects at high risk of developing colorectal neoplasia but the procedure is expensive, time consuming and occasionally hazardous. Faecal occult blood tests can be prepared at home and are cheap, simple and safe. Hemeselect is an immunological faecal occult blood test that is more sensitive for colorectal cancer than Haemoccult. The aim of this study was to determine the sensitivity of the Hemeselect test for asymptomatic colorectal neoplasia in subjects at high risk of the disease who were undergoing colonoscopy, thus assessing its suitability as an alternative means of screening high-risk groups. A total of 919 asymptomatic subjects were asked to complete Hemeselect tests. These were completed satisfactorily by 808 individuals (compliance rate 88 per cent) and were positive in 164 patients (20 per cent). At colonoscopy 11 cancers were detected in ten patients (seven Hemeselect positive) and 36 (16 Hemeselect positive) had at least one adenoma 1 cm or more in diameter. The test sensitivites of Hemeselect for carcinoma and large (1 cm or more) adenomas were 70 and 44 per cent respectively. In a subset of 417 subjects who also completed Haemoccult tests, the sensitivities were 33 and 18 per cent. Hemeselect specificity is 88 per cent compared with 98 per cent for Haemoccult. While the sensitivity of Hemeselect is higher than that of Haemoccult, it is still insufficient to replace colonoscopy in high-risk groups. PMID- 7795995 TI - Risk factors in patients presenting as an emergency with colorectal cancer. AB - Of 905 patients with colorectal cancer admitted to a single district general hospital, 272 (30 per cent) were admitted as emergencies. Emergency patients had more advanced tumours (Dukes stage B and C 96 per cent versus 88 per cent of those admitted electively, P < 0.006), a shorter history (median 3 versus 11 weeks, P < 0.0001), were less likely to be fully ambulatory (44 versus 80 per cent, P < 0.0001) and more likely to have abdominal pain (74 versus 51 per cent, P < 0.001) and vomiting (40 versus 10 per cent, P < 0.0001). More emergency patients were given stomas (56 versus 35 per cent, P < 0.0001) and died in hospital (19 versus 8 per cent, P < 0.0001). Of those who survived to be discharged, patients admitted as an emergency spent longer in hospital (median stay 16 versus 13 days, P < 0.0001) and had a poorer overall 5-year survival rate (29 versus 39 per cent, P = 0.0001). Emergency patients were significantly older (median 74 versus 72 years, P = 0.04) and much more likely to be widowed (41 versus 27 per cent, P = 0.0002) than those admitted for elective surgery. If the personal and resource disaster of emergency colorectal cancer admission is to be reduced, screening strategies targeted by demographic characteristics require investigation. PMID- 7795996 TI - Laparoscopic caecopexy for caecal volvulus. PMID- 7795997 TI - Foley catheter-assisted sutured colorectal anastomosis. PMID- 7795998 TI - Seat-belt compression appendicitis. PMID- 7795999 TI - Island advancement flaps in the management of anal fissures. AB - The classic high-pressure fissure responds well to lateral internal sphincterotomy. The management of recurrent fissures and those that occur in patients with weak sphincters is open to debate. An island advancement flap technique used in 21 patients is described with the above criteria. Preoperative median resting anal pressure was 66 (range 43-90) cmH2O and median maximal squeeze pressure was 132 (range 76-193) cmH2O, values that were significantly lower than in controls and those with classic fissure. Endoanal ultrasonography in 15 of these patients showed defects in the anal sphincters. All flaps healed primarily with preservation of sensation. Perfect continence was maintained in all patients. Follow-up was for a median of 18 (range 2-28) months. There were no serious complications. All fissures healed with minimal postoperative discomfort. This procedure provides a useful alternative for symptomatic anal fissures, in which a sphincter-weakening procedure might jeopardize continence. PMID- 7796000 TI - Presentation of comparative audit data. AB - The Royal College of Surgeons of England organizes a voluntary comparative audit service for its general surgical fellows. To date, the information from the audit has been presented purely descriptively, which does not take account of statistical variability and the effects of differences in case mix between the participants. A new approach to the presentation of these data, based on statistical modelling of the effects of case mix, is presented. The approach is illustrated in an application based on data relating to 136203 admissions reported by 110 surgeons. The result of adjusting for case mix is a substantial change in the relative performance of the participating surgeons, which demonstrates the folly of attempting to compare surgical performance on the basis of a measure as crude as the unadjusted mortality rate. Further development of the statistical modelling is required, but this new statistical approach appears to enhance greatly the credibility of the audit data, by quantifying its strengths and limitations. PMID- 7796001 TI - Oesophageal acid clearance in patients with severe reflux oesophagitis. AB - Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease. PMID- 7796004 TI - Radical orchidectomy and benign testicular conditions. AB - The records of 149 patients who underwent testicular exploration for suspected malignancy were reviewed retrospectively. Malignancy was confirmed in 102 patients but benign pathology was noted in 47. Patients with benign disease were older, more likely to be Asian, gave a longer history and on examination were less likely to have a testicular mass. Increased levels of tumour markers, and ultrasonographic and operative appearance of the testis were highly predictive; with ultrasonography having a sensitivity of 100 per cent but a specificity of only 36 per cent for malignancy. Preoperative ultrasonography and an awareness of the potentially benign nature of many lesions with the use of frozen-section biopsy, where appropriate, may allow a decrease in the currently high rate of unnecessary orchidectomy without missing testicular malignancy. PMID- 7796003 TI - Breast cancer in a trans-sexual man receiving hormone replacement therapy. PMID- 7796005 TI - New method to evaluate the therapeutic value of lymph node dissection for gastric cancer. AB - The results of 1281 potentially curative resections for advanced gastric cancer performed at the National Cancer Center Hospital between 1972 and 1986 were studied using a novel approach which circumvents the stage migration phenomenon. The incidence of metastasis and the 5-year survival rate of patients with positive nodes were calculated independently for each lymph node 'station', without any reference to overall pathological nodal stage. The therapeutic value of extended lymph node dissection was estimated by multiplication of incidence of metastasis and percentage 5-year survival rate of patients with metastasis for each station. The incidence of metastasis ranged from 2.4 per cent to 66 per cent and the 5-year survival rate of affected patients from 0 to 58.7 per cent in perigastric stations, depending on the site of the primary tumour. The incidence of metastasis was between 3.0 per cent and 44.4 per cent in the second tier of nodes (n2), and the 5-year survival rate ranged from 0 per cent to 47.5 per cent. The majority of second-tier stations showed evidence of benefit from node dissection. PMID- 7796002 TI - Immediate and early follow-up results of purse spray thrombolysis in patients with peripheral ischaemia. AB - Pulse spray thrombolysis is a technique of accelerated peripheral thrombolysis which has been evaluated in 38 patients, 29 with threatened limb viability and nine with a viable but critically ischaemic limb. The median length of occlusion was 26.5 (range 3-65) cm. The lytic agent used was recombinant tissue plasminogen activator (rtPA), injected manually via a pulse spray catheter at a concentration of 0.33 mg/ml and a bolus size of 0.2 ml. The median total dose of rtPA was 18 (range 5-35)mg. Patency and flow were completely restored in 34 of 38 patients and clinical success at 30 days was maintained in 27 of 38. The median lysis time was 120 (range 35-1125) min, compared with a median duration of 1545 (range 42 5760) min in 120 consecutive patients previously treated with conventional low dose infusion thrombolysis using rtPA. This represents a 12-fold reduction in lysis time (P < 0.001). The overall estimated cumulative limb salvage rate for the 38 patients who entered the study was 84 per cent and the cumulative patency rate for the 34 patients in whom patency was restored was 74 per cent at 18 months follow-up. Pulse spray thrombolysis rapidly restores patency with good limb salvage at 30 days; the benefit is sustained even in patients with limbs at immediate risk of irreversible ischaemic injury who are not considered suitable for conventional thrombolysis. PMID- 7796006 TI - Laparoscopy in the management of patients with cancer of the gastric cardia and oesophagus. AB - The role of laparoscopy in determining suitability for resection was prospectively evaluated in 244 patients with cancer of the gastric cardia and oesophagus. Laparoscopy enabled detection of inoperable disease in 92 patients (38 per cent), several of whom had more than one contraindication to surgery. Hepatic metastases (n = 75, 31 per cent), extensive peritoneal (n = 25, 10 per cent) or lymph node involvement (n = 5, 2 per cent) and direct invasion of the liver or colon (n = 5, 2 per cent) were considered contraindications to surgery. Laparoscopy was poorly tolerated in a further 11 (5 per cent) patients, who were not considered suitable for resection. Extra-abdominal metastatic disease was detected in 17 patients who appeared normal at laparoscopy, and a further six patients refused surgery. The remaining 118 patients underwent laparotomy with a view to resection which was successful in 85 (72 per cent). Laparoscopy thus prevented ill-advised laparotomy in 103 patients (42 per cent), either because of extensive intra-abdominal disease or poor tolerance to anaesthesia. Laparoscopy may be a valuable investigation when used to assess the feasibility of resection. PMID- 7796007 TI - Splenic abscess. PMID- 7796008 TI - Preoperative assessment of lymph nodes in the prediction of disease spread and outcome in cancer of the thoracic oesophagus. AB - Prospective assessment of lymph node status, based on the findings of computed tomography, external ultrasonography and palpation, was compared with clinical results in 179 patients who underwent oesophagectomy with systematic node dissection. Preoperative findings for each node group were classified into four grades: involvement not suspected (-); possible involvement (+/-); probable involvement (+); and definite involvement (++). When only (++) or (+) assessment was categorized as positive, the specificity was more than 94 per cent, although the sensitivity was less than 40 per cent. The preoperative assessment correlated significantly with the incidence of node involvement (P < 0.02), the degree of lymphatic invasion (P < 0.0001) and outcome after operation. For patients with all nodes assessed as (-), the 5-year survival rate was 70 per cent, compared with 26 per cent for those with nodes assessed as (++), P = 0.001. Preoperative assessment provided useful information on nodal status. PMID- 7796009 TI - Helicobacter pylori infection in perforated peptic ulcer disease. AB - This study examined a possible aetiological agent, namely, Helicobacter pylori, in perforated peptic ulcer disease and its relationship to persisting ulcer. Twenty-nine patients with perforated peptic ulcer underwent simple closure of the perforation at laparotomy. A 13C urea breath test carried out on the eighth day after operation was positive in 24 patients. Fourteen of 17 patients who underwent upper gastrointestinal endoscopy 6 weeks after discharge from hospital had a positive 13C urea breath test. The biopsy urease test performed on mucosal samples taken at endoscopy was positive in 12 of these 14 patients, indicating continuing active infection with H. pylori. Seven patients with positive 13C urea breath and biopsy urease tests had persisting duodenal ulceration. None of the three patients with a negative 13C urea breath test had evidence of duodenal ulceration at endoscopy. The association between a high rate of duodenal ulcer persistence and a high incidence of H. pylori infection suggests that antibiotic therapy to eradicate this microorganism should be given to all patients with perforated peptic ulcer disease. PMID- 7796010 TI - Laparoscopic technique for small bowel biopsy. PMID- 7796011 TI - High amplification of the hst-1 gene correlates with haematogenous recurrence after curative resection of oesophageal carcinoma. AB - Amplification of the hst-1 gene was examined in 82 patients with oesophageal carcinoma by dot blot hybridization to assess the potential of haematogenous recurrence after curative resection. Intensity of amplification was considered negative (one- to twofold increase) in 45 patients, low (three-sixfold increase) in 19 and high (greater than sevenfold) in 18. Haematogenous recurrence after curative resection was found in seven of eight patients with high amplification and was significantly higher in such patients than in those without amplification (P < 0.05). The finding that sevenfold or greater amplification of the hst-1 gene seems to be associated with haematogenous recurrence of oesophageal cancer after resection may serve to assess the clinical outcome. PMID- 7796012 TI - Effect of starch-containing glove powder on wound healing in the rat. AB - The effect of the starch-containing powder BioSorb on wound healing was examined in an immunocompetent and a T cell-deficient animal model. Wounds were tested by tensionometry to give values of resilience, ultimate strength, toughness and extension. Starch significantly decreased the resilience (P < 0.03), ultimate strength (P < 0.004), and toughness (P < 0.006) of wounds in the immunocompetent model but was not shown to affect the healing of wounds in T cell-depleted animals. When the uncontaminated wounds of the two groups were compared, those from T cell-depleted animals were tougher (P < 0.04) and less extensile (P < 0.0002). These results suggest that starch impairs wound healing by its effect on the T cell-mediated immune system, and that this system may also be involved in regulation of the reparative process because its absence leads to tougher wounds. PMID- 7796013 TI - H-hernioplasty: a tension-free repair for umbilical hernia. PMID- 7796014 TI - Long-term survival in children with renal carcinoma: report of two surgically treated cases. PMID- 7796017 TI - Choledochal cysts in adults. AB - Fourteen adults who presented with choledochal cysts were studied. Symptoms in most cases were non-specific, which resulted in delayed diagnosis. Associated extracystic hepatobiliary disease occurred in 11 patients, including two with cholangiocarcinoma. Nine patients underwent total cyst excision (eight Todani classification type I and one type II), while four with type IVa cysts had excision of the extrahepatic cyst component. There were no surgical deaths. One patient with metastases was treated conservatively. Median follow-up was 6.5 years. Two of three patients who developed anastomotic strictures underwent successful revision surgery, while one with secondary sclerosing cholangitis developed biliary cirrhosis and died from hepatic failure after 8 years. Both patients with cholangiocarcinoma have died. Ten survivors are well and one patient was lost to follow-up. This study highlights the complexity of choledochal cysts in adults and emphasizes the need for earlier diagnosis and treatment. Cyst excision should be performed where possible, with reconstruction modified to deal with the cyst type as well as associated hepatobiliary pathology. PMID- 7796016 TI - Morbidity and mortality after hepatic resection of metastases from colorectal cancer. AB - A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results. PMID- 7796015 TI - Laparoscopic cholecystectomy minimally impairs postoperative cardiorespiratory and muscle performance. AB - Surgery elicits a subjective feeling of postoperative fatigue, at least partly related to an impairment in cardiorespiratory function and muscle performance. Laparoscopic surgery is reported to impair the patient's condition minimally. The aim of this study was to assess exercise performance in patients scheduled for elective laparoscopic cholecystectomy. Nine patients assessed as having American Society of Anesthesiologists (ASA) grade I were enrolled in the study. Subjective feelings of fatigue (measured on a visual analogue scale), and heart rate, systemic arterial pressure oxygen consumption and carbon dioxide production responses to graded exercise testing, were assessed before operation and on days 3 and 10 after operation. There were no significant differences in any of these measurements, at rest or during exercise, between the preoperative and postoperative values. Uncomplicated laparoscopic cholecystectomy does not impair postoperative cardiorespiratory and muscle performance or induce significant postoperative fatigue in patients with ASA I, allowing rapid recovery. PMID- 7796019 TI - Experimental laparoscopic liver resection with a multimodal water jet dissector. PMID- 7796018 TI - Improved outcome for children with hepatoblastoma. AB - Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma. PMID- 7796020 TI - Peritoneal seeding of pancreatic cancer following transperitoneal biliary procedures. PMID- 7796021 TI - A triple bypass procedure for advanced carcinoma of the neck of gallbladder. PMID- 7796022 TI - Management of Mirizzi syndrome by laparoscopic cholecystectomy and laparoscopic ultrasonography. PMID- 7796023 TI - Combined liver transplantation and pancreatoduodenectomy for irresectable hilar bile duct carcinoma. PMID- 7796025 TI - Intraluminal stapled laparoscopic cystogastrostomy for treatment of pancreatic pseudocyst. PMID- 7796024 TI - Lymph node metastases in carcinoma of the head of the pancreas region. AB - Histopathological examination of lymph node metastatic involvement in 139 specimens obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy combined with wide resection of lymph nodes was performed, to clarify the critical areas of lymph node dissection in patients with carcinoma of the head of the pancreas region. Perigastric lymph node involvement in patients with carcinoma of the head of the pancreas was 14 per cent, in those with carcinoma of the distal bile duct 0 per cent and in those with carcinoma of the papilla of Vater 4 per cent. Para-aortic lymph node involvement in patients with carcinoma of the head of the pancreas, the distal bile duct and the papilla of Vater was 26, 9 and 0 per cent, respectively. On the basis of these results, pylorus-preserving pancreatoduodenectomy is indicated in almost all patients with carcinoma of the distal bile duct and the papilla of Vater. In patients with carcinoma of the head of the pancreas, however, wide dissection of lymph nodes, including para-aortic lymph nodes, should be carried out because of the relatively high incidence of para-aortic lymph node involvement. PMID- 7796026 TI - Modified dunking pancreatojejunostomy for a soft pancreas. PMID- 7796027 TI - Spontaneous splenic rupture during total vascular occlusion of the liver. PMID- 7796028 TI - Risk-adjusted analysis of surgeon performance: a 1-year study. AB - A 1-year prospective analysis was undertaken of all non-day-case general surgery in a district general hospital. Using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system 3004 patients were assessed. From the predictions of mortality and morbidity so obtained, a quality measure, the ratio of observed to expected numbers of deaths and complications (O:E ratio) was determined for each surgeon, both overall and within specialty zones. The present study demonstrates the serious hazard in using 'raw' uncorrected mortality and morbidity statistics to compare surgeon performance. Mortality rates varied from 1.0 to 4.9 per cent whereas O:E ratios ranged from 0.83 to 1.06; morbidity rates varied from 5.3 to 12.6 per cent with O:E ratios 0.86-1.02. Great misunderstanding may result from the publication of surgeon or hospital 'league tables'. The present study demonstrates a technique that might allow surgeon performance to be monitored adequately and accurately. PMID- 7796029 TI - Lateral tracheostomy in patients with cervical spinal cord injury. PMID- 7796032 TI - Early results with Lichtenstein tension-free hernia repair. PMID- 7796031 TI - Early results with Lichtenstein tension-free hernia repair. PMID- 7796030 TI - Human intraperitoneal fibrinolytic response to elective surgery. AB - Intra-abdominal adhesions develop in over 90 per cent of patients undergoing laparotomy. Peritoneal fibrinolysis is believed to be important in the pathophysiology of adhesion formation. This study investigated the fibrinolytic response of postoperative peritoneal fluid in 12 patients undergoing elective laparotomy. There was a significant reduction in the plasminogen activating activity to undetectable levels at 24 h, which was sustained at 48 h (P < 0.05). While there was an early reduction in the concentration of tissue plasminogen activator (median 40.0, 28.2, 16.3 and 31.9 ng/ml at 2, 6, 24 and 48 h respectively; P < 0.05), the abolition of functional fibrinolytic activity appeared to be secondary to a marked increase in the concentration of plasminogen activator inhibitor (PAI) 1 (median 86, 196, 800 and 730 ng/ml at 2, 6, 24 and 48 h respectively; P < 0.05) and PAI-2 (median less than 6, 12, 155 and 245 ng/ml at 2, 6, 24 and 48 h respectively; P < 0.05). This reduction in the plasminogen activating activity of peritoneal fluid may favour the formation of permanent fibrous adhesions following surgery. PMID- 7796034 TI - Randomized trial of modified Bassini versus Shouldice inguinal hernia repair. Further comment. PMID- 7796033 TI - Early results with the Lichtenstein tension-free hernia repair. PMID- 7796035 TI - Long-term results of highly selective vagotomy: a prospective study with implications for future laparoscopic surgery. PMID- 7796036 TI - Stripping of the long saphenous vein in the treatment of primary varicose veins. PMID- 7796037 TI - Radiotherapy and management of the axilla in early breast cancer. PMID- 7796038 TI - Portal pyaemia following flexible sigmoidoscopy. PMID- 7796039 TI - Diabetes impairs the development of early strength, but not the accumulation, of collagen during intestinal anastomotic healing in the rat. PMID- 7796040 TI - Kidney retrieval from asystolic donors: a valuable and viable source of additional organs. PMID- 7796041 TI - Patterns of reflux in recurrent varicose veins assessed by duplex scanning. PMID- 7796042 TI - Comparative audit of colorectal resection with the POSSUM scoring system. PMID- 7796043 TI - Simple method of tightening cutting setons. PMID- 7796044 TI - Enantioselective deoxygenation of alkyl aryl sulfoxides by DMSO reductase from Rhodobacter sphaeroides f.s. denitrificans. AB - The substrate specificity and enantioselectivity of DMSO reductase from Rhodobacter sphaeroides f.s. denitrificans were studied on a series of alkyl aryl sulfoxides as substrate. The enzyme was found to catalyze deoxygenation of (S) sulfoxides predominantly. (R)-Sulfoxides were recovered with a high enantiomeric excess. PMID- 7796045 TI - The receptor binding affinity of monocyclic [Ala3,Xaa11]endothelin-1 analogs correlates with inducible helix length. AB - Endothelin-1, a bicyclic 21-amino acid peptide with disulfide bridges between cysteines 1 and 15 as well as between cysteines 3 and 11, has been reported to be partially helical based on both CD and NMR data. However, this remains an area of controversy with some claims that CD data indicate no alpha-helical structure (Calas, B.; Harricane, M.-C.; Gulmard, L.; Heitz, F.; Mendre, C.; Chabrier, P.E.; Bennes, R. Peptide Res. 1992, 5, 97) and a recent X-ray crystal structure placing the helix at a different locus (Janes, R.W.; Peapus, D.H.; Wallace, B.A. Structural Biology 1994, 1, 311). The CD studies reported herein indicate that the helical structures reported in NMR studies (e.g. Andersen, N.H.; Chen, C.; Marschner, T.M.; Krystek, Jr. S.R.; Bassolino, D.A. Biochemistry 1992, 31, 1280) apply to pure aqueous media as well. The helix located from Lys9 to the Cys15/His16 juncture is ca 75% populated in pH 4 aqueous buffer. Titration difference CDs reveal that the helix extent increases by one to two residues and that the 'helical conformation' is more completely populated upon addition of TFE to 50+ volume-%. Comparison with a more helical analog suggests that the helix propagates towards (but not to the end of) the C-terminus upon fluoroalcohol addition. A variety of monocyclic derivatives of [Nle7] ET-1 lacking the 3,11 disulfide were evaluated for biological activity and examined by TFE titration difference CD. The series included an Aib11 and a Pro11 analog. The helix promoting Aib analog was the most active while the Pro analog exhibited significantly lower vasoconstrictor activity and binding affinity for the ETA receptor. All of the monocyclic analogs became significantly more helical upon addition of fluoroalcohols. The inclusion of a proline residue at position 11 does not preclude helix formation upon addition of fluoroalcohols. Rather, helix formation is relatively easily induced but limited to a 5 residue span. Apparently this is insufficient to orient required side chains optimally for interaction with the ETA receptor. For the 1,15-monocyclic analogs differing only at position 11, ETA binding affinity and vasoconstrictor potency correlate with the facility which a 7-8 residue long helix can be induced. This presumably includes the segment Glu10-->Cys15 in all cases and may represent the full sequence from Lys9-->His16. CD studies also reveal that the C-terminal fragment of endothelins is not a fully disordered 'random coil' either alone or attached to the endothelin core. PMID- 7796046 TI - Isoxazoline derivatives as potential inhibitors of the proteolytic enzymes human leukocyte elastase, cathepsin G and proteinase 3: a structure-activity relationship study. PMID- 7796047 TI - Synthesis and biological properties of a series of optically active 2 oxaisocephems. AB - A novel series of (6S, 7S)-3,7-disubstituted-8-oxo-1-aza-4-oxabicyclo[4.2.0]oct-2 ene-2- carboxylic acids 9a-o, parenteral optically active 2-oxaisocephems, was synthesized, and in vitro and in vivo activities were determined against Gram positive and Gram-negative bacteria. The 7-[2-(2-aminothiazol-4-yl)-2-(Z) cyclopentyloxyimino]acet arnido derivatives, 9g, 9m and 9o, had enhanced antibacterial activity against Gram-positive organisms including methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis while maintaining Gram-negative activity. It is also significant that these compounds showed more potent activity against MRSA and E. faecalis isolates than cefuzonam (10) and flomoxef (12), which are the most popular third-generation antibiotics. The combination of the 7-[2-(aminothiazol-4-yl)-2-(Z) cyclopentyloxyimino]acetamido group and 2-oxaisocephem nucleus contributes to the increased antibacterial activity against these clinical isolates. The 7-[2-(2 aminothiazol-4-yl)-2-(Z)-cyclopentyloxyimino]acet ami do derivative 9g provided good subcutaneous efficacy and exhibited more potent activity than cefmenoxime (11) against the systemic infection with S. aureus Smith in mice. The compound 9a with a [2-(2-aminothiazol-4-yl)-2-(Z)-methoxyimino]acetamido group at the 7 position showed high in vivo efficacy on the experimental infection caused by Escherichia coli No. 29 in mice. PMID- 7796048 TI - Synthesis and anti-HIV activity of new urea and nitrosourea derivatives of diamino acids. AB - A series of N1-methyl,N1-allyl,N1-(2-chloroethyl) and N1-propargyl urea and nitrosourea derivatives of diamino acids (L-ornithine and L-lysine) was synthesized and was shown to have weak activity in counteracting the cytopathic effects of the HIV-1 on a T4 lymphocyte cell line (CEM-IW). However, selected compounds may possess some immunomodulatory activity. PMID- 7796049 TI - Facile synthesis of a new type of iminosugar: a nitrogen atom is in the anomeric position. PMID- 7796050 TI - Structure-activity studies of sulfate transfer: the hydrolysis and aminolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS). AB - The pH-rate profile for the hydrolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in aqueous solution has been measured. Comparison with other data suggests that hydrolysis occurs by almost complete unimolecular elimination of sulfur trioxide, with weak involvement of a molecule of water in the transition state. The catalytic power (kcat/kuncat) of the sulfotransferases is estimated to be in the order of 10(10)-10(12). Amines--exemplified by morpholine--react spontaneously with PAPS in water at 39 degrees C by attack at both sulfuryl and (5')phosphoryl groups in a ratio of 2:3. The mechanism of activation of the coenzyme, PAPS, by the sulfotransferases that catalyse N-sulfation must involve suppression of its native N-phosphorylating reactivity and specific enhancement of its N-sulfating reactivity. Studies of the aminolysis of the coenzyme in aprotic solvent-water mixtures suggest how this might be accomplished. PMID- 7796051 TI - The cyano-NNO-azoxy function in the design of an irreversible label for alpha 1 adrenoreceptors. AB - A potential alpha 1-adrenergic irreversible antagonist 6, containing the cyano NNO-azoxy function was synthesized and tested. The effects of norepinephrine on rat thoracic aorta were irreversibly blocked by this compound at the concentration of 1 x 10(-5) M after 60 minutes. Binding studies showed that 6, at 1 x 10(-6) M, did not modify the KD of Prazosin and caused a 30% decrease of the Bmax. Substitution in 6 of the bis (2-chloroethyl)amino moiety for the cyano-NNO azoxy function afforded 7 which behaves as an irreversible antagonist able to change KD of Prazosin without influencing Bmax. PMID- 7796052 TI - Dioxides of bicyclic thiadiazines: a new family of smooth muscle relaxants. AB - The synthesis of dioxides of bicyclic thiadiazine related to diazoxide has been achieved. In a preliminary test, some of these compounds show smooth muscle relaxation similar to that obtained with the reference standard diazoxide. PMID- 7796053 TI - The Gabriel-Colman rearrangement in biological systems: design, synthesis and biological evaluation of phthalimide and saccharin derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3. AB - The results of a structure-activity relationship study focusing on the interaction of a series of phthalimide and saccharin derivatives with leukocyte elastase, cathepsin G and proteinase 3 are described. The phthalimide derivatives were found to be inactive while some of the saccharin derivatives were found to be fair inhibitors of these enzymes. PMID- 7796054 TI - The mechanism of Escherichia coli tryptophan indole-lyase: substituent effects on steady-state and pre-steady-state kinetic parameters for aryl-substituted tryptophan derivatives. AB - We have examined the reaction of Escherichia coli tryptophan indole-lyase with fluoro, chloro, methyl and hydroxytryptophans using steady-state kinetics, rapid scanning and single wavelength stopped-flow spectrophotometry, and rapid chemical quench methods. All of the 16 tryptophan derivatives examined are substrates for alpha, beta-elimination catalyzed by tryptophan indole-lyase. The steady-state kinetic parameter, kcat/Km, did not show a consistent trend with the steric bulk of the substituent, but Km increased for larger substituents. Rapid-scanning stopped-flow spectra show that all tryptophan analogues undergo covalent reaction with the pyridoxal-5'-phosphate cofactor to give equilibrating mixtures of external aldimine and quinonoid intermediates, but the relative amounts of each intermediate are strongly dependent on the nature and position of the substituent. The dissociation constants for external aldimine formation, Kd, obtained from single-wavelength stopped-flow experiments decreased for most substituted tryptophans, which suggests that part of the binding energy is derived from hydrophobic interactions between the enzyme and the indole ring of tryptophan. In contrast, the rate constants of quinonoid intermediate formation and reprotonation and of indole elimination were quite variable, depending on the position and the nature of the substituent. Overall, 6-substituted tryptophans have the most consistent reactivity, which indicates that there may be space in the enzyme active site near the 6-position. There is a good linear correlation between log (kcat/Km) and log (kf/Kd) (apparent second order rate constant for quinonoid intermediate formation), with a slope of 0.66. This suggests that quinonoid intermediate formation contributes only about 66% of the activation energy for the reaction, and thus a later step in the reaction must be partially rate-limiting. Rapid chemical quench experiments demonstrate a 'burst' of indole in the reaction of L-tryptophan under single turnover conditions, confirming that a step subsequent to the elimination is partially rate-determining. In contrast, 5-methyl-L-tryptophan does not exhibit a significant 'burst', suggesting that 5 methylindole elimination is nearly completely rate-determining. These results support the proposed mechanism and demonstrate that there are significant effects of aryl substituents on the distribution of covalent intermediates and on the rate-determining step in the alpha, beta-elimination reaction catalyzed by E. coli tryptophan indole-lyase. PMID- 7796055 TI - Visualizing taste papillae in vivo with scanning electron microscopy of a high resolution cast. AB - A method using polyvinylsiloxane (PVS), a high-resolution dental impression material, to obtain negative images of lingual surfaces is described. Epoxy-resin tongue replicas made from these impressions were examined with scanning electron microscopy (SEM). This method has been developed to visualize structural details of the tongue surface of living human beings and laboratory animals. The utility of the method is demonstrated with hamster tongues, which have well-defined fungiform papillae with single taste pores, and human tongues, which have more variable surface structures. Replicas made from PVS impressions of tongues of living hamsters were compared with the same tongues after fixation. The replicas contained much of the detail present in fixed tongues. With SEM, it was possible to identify individual fungiform papillae, which contained depressions with the size and the location of hamster taste pores. Individual papillae could also be recognized in human-tongue replicas, but taste pores could not be identified with certainty. These replicas provide permanent, three-dimensional records of tongue topography that could be used to document changes due to trauma, disease and aging. PMID- 7796056 TI - Taste bud cell generation in the perihatching chick. AB - Chick taste bud primordia initially appear in late gestation on embryonic day 17 (E17), 4 days before hatching. To track DNA synthesis and subsequent taste bud cell proliferation between E17 and the second day post-hatching (H2), single 25 muCi injections of tritiated thymidine (specific activity = 72.5 Ci/mmol) were administered in ovo during E15, E16, E17 or E18. Anterior mandibular oral epithelium was processed for light microscopic autoradiography. Sections through each taste bud's center were analysed for label (> or = 6 silver grains/gemmal cell nucleus), and bud diameter. Results indicated a major part of gemmal cell DNA synthesis does not occur until after E19 irrespective of the day of thymidine injection, suggesting postmitotic or quiescent (decycled) cells assemble to form the early bud primordium (E17-19) based on local tissue interactions. All buds examined from E20-H2 contained labelled cells. The day of injection was important since 5-day survival cases after E16 injection yielded about 25% the number of labelled cells/bud as compared with equivalent survival cases following E17-18 injections. These results are discussed with respect to parallel changes in bud shape and increasing bud diameter, and cell proliferation in possible extra- and intragemmal sources of bud cells. PMID- 7796058 TI - Effect of amiloride on the taste of NaCl, Na-gluconate and KCl in humans: implications for Na+ receptor mechanisms. AB - Sodium-salt transduction in many species may be mediated by both apical and submucosal ion channels on the taste receptor cell membrane. The apical ion channel is blockable by the diuretic amiloride, whereas the submucosal pathway is not. Sodium salts with small anions, such as NaCl, can stimulate submucosal as well as apical ion channels; sodium salts with large anions, such as Na gluconate, activate primarily the apical channels. In humans, reports on the effects of amiloride on the taste of NaCl are conflicting and no data exist on the effects of amiloride on organic sodium salts. In the present experiment, subjects gave magnitude estimates of the total intensity and of each of the basic taste qualities for NaCl, Na-gluconate and KCl. Five concentrations of each of these stimuli were presented to the anterior tongue following distilled water adaptation and after amiloride treatment. There was a significant decrease in the total taste intensity of NaCl and Na-gluconate after amiloride, but no effect on KCl. The saltiness of all three salts was unaffected, but amiloride decreased the perceived sourness of the sodium salts. KCl sourness was unaffected by amiloride. There was a proportionately larger effect of amiloride on Na-gluconate than on NaCl, which is consistent with a larger role for the apical ion channel in Na gluconate transduction. However, an appreciable amiloride-insensitive component is present for both NaCl and Na-gluconate, suggesting that an amiloride insensitive pathway also plays a role in the transduction of both sodium salts. These data support the hypothesis that an amiloride-sensitive transduction component exists in humans, but suggest that it is considerably smaller than in many other species. PMID- 7796057 TI - Pain-reducing properties of sucrose in human newborns. AB - To assess the characteristics of sucrose as a pain-reducing substance, crying in 72 newborn humans during and after blood collection via heel prick was determined. In the first study infants drank 2 ml of water or 2 ml of a 0.17-0.34 or 0.51-M sucrose solution 1 min prior to blood collection. In the second experiment, a delay of 30, 60, 90, 120 or 240 s was imposed between sucrose intake and the initiation of blood collection. The dose-response function for concentration was flat. The most effective time delay was 120 s. The effectiveness of the 2-min interval accords with previous findings of endogenous opioid release caused by sucrose taste. The flat dose-response function extends findings in rats and humans that the calming and pain-reducing effects of sucrose are not influenced by either concentration or volume, suggesting that the transduction from gustatory afferent to opioid-mediated efferent is of an on-off nature and not graded. PMID- 7796059 TI - The taste-active regions of monellin, a potently sweet protein. AB - Monellin, a protein found in the berries of the West African plant Dioscoreophyllum cumminsii, is one of the most potently sweet compounds known. The native three-dimensional structure of monellin is required for sweetness, and this protein has been the subject of intense research in an attempt at understanding the structural basis for its taste activity. We have used structure based site-directed mutagenesis to delineate the taste-active site(s) of monellin, and we present these results, along with similar work from M. Kohmura, Y. Ariyoshi and coworkers, in the light of the three-dimensional structure of this protein. The mutagenesis work suggests that at least four residues, located N-terminal to the alpha-helix, form part of a taste-active region of monellin. In addition, there is evidence that a second region, formed by residues in the fourth and fifth beta-strands, may also be contributing to monellin's activity. PMID- 7796060 TI - Porcine VEG proteins and tear prealbumins. AB - Small soluble proteins, belonging to the lipocalin family are secreted in large amounts by tongue von Ebner's glands and lachrymal glands. In humans, the lingual protein, called VEG, and the lachrymal protein, called tear prealbumin, have shown identical cDNA sequences. In the pig, we have purified homodimeric proteins with subunits of 17 kDa, both from von Ebner's glands and from lachrymal glands. In both cases, the proteins can be resolved into two isoforms on a chromatofocusing column. Partial aminoacid sequences and full cDNA sequences have been obtained for the more abundant forms purified from both tissues. The two proteins appear to be identical, as in humans. The reason why the same protein is expressed in different tissues, as well as its physiological function, still remain to be clarified. PMID- 7796062 TI - ECT at mid-decade: two steps forward, one step back. PMID- 7796061 TI - Variation in odor thresholds for l-carvone and cineole and correlations with suprathreshold intensity ratings. AB - Specific anosmias have been reported for l-carvone and cineole, two compounds of importance in food flavor perception. Detection thresholds were assessed in groups of 50+ individuals by ascending forced-choice tests conducted in quadruplicate. Wide individual differences in thresholds were observed. Within the same session, threshold correlations were in the range of +0.8 to +0.9, showing good short-term reliability. Correlations with suprathreshold ratings were moderate (in the range of r = -0.5) after subtraction of false positive ratings for blank samples. However, a cineole mixture experiment failed to show any differences between subgroups that were previously classified as high or low sensitivity on the basis of threshold measurements. Re-testing selected groups after a period of months showed considerable within-individual variation in the thresholds, especially for l-carvone. These results call into question the stability and utility of threshold classification for these two compounds. PMID- 7796063 TI - Maintenance ECT: indications and outcome. AB - Maintenance electroconvulsive therapy (M-ECT) is used to prevent recurrence of depression. Indications regarding patient selection criteria and efficacy are uncertain, in part because data are lacking. Comparison of M-ECT patients (N = 21) with controls demonstrates that M-ECT is chosen for patients whose course is characterized by multiple hospitalizations and failure to adequately respond to other therapies. M-ECT patients were exposed, on average, to 10 different psychotropic medications, including five trials of tricyclic antidepressants. Greater than half of their cumulative hospitalizations were for ECT. Their rate of rehospitalization decreased by 67% after institution of prophylactic M-ECT, demonstrating treatment efficacy. A tendency toward relapse and rehospitalization remains when M-ECT patients are compared to controls. PMID- 7796064 TI - Prolactin release and clinical response to electroconvulsive therapy in depressed geriatric inpatients: a preliminary report. AB - Fifteen inpatients (nine women, six men) aged 50-86 years with DSM-IIIR major depression were treated with electroconvulsive therapy (ECT). Electrode placement (unilateral versus bilateral) and total number of treatments were determined by the patients' own psychiatrists according to clinical indications. Prolactin (PRL) was determined after the 1st, 6th, 7th, 9th, 11th, and final ECT treatments. Subjects were rated with the Hamilton Depression Rating Scale (HDRS) at baseline, after the sixth ECT treatment, and upon completion of ECT. PRL response to unilateral ECT was consistent across treatment for each subject. Percentage PRL increase was significantly higher for bilateral than unilateral ECT (alpha = 0.05). Subjects with final HDRS of < 12 tended to have greater peak, increase, and percentage increase PRL at the first unilateral treatment than subjects with final HDRS of at least 12; these trends approached statistical significance (Kruskal-Wallis one-way analysis of variance; peak: p = 0.059, chi = 3.556, df = 1; increase: p = 0.099, chi = 2.722, df = 1; percentage increase: p = 0.099, chi = 2.722, df = 1). Decrease in HDRS after the sixth treatment failed to show a statistically significant relationship to any PRL parameter at the initial unilateral treatment. Further studies are needed to characterize the relationship between PRL response, seizure activity, and stimulus dosing. PMID- 7796065 TI - Effects of electroconvulsive therapy on plasma GABA. AB - There are no published data on the effects of seizures on indices of gamma aminobutyric acid (GABA) function in human subjects. In study 1, the effects of electroconvulsive therapy (ECT) on free plasma GABA were studied in 39 inpatients with major depressive disorder. Acutely after ECT, free plasma GABA was significantly reduced for up to 1 h after seizure termination, and this finding replicated strongly in a subgroup of six patients who received a second course of ECT. In a second study at a different site that compared sham ECT and real ECT in seven patients, some doubt was raised about the replicability of the acute effect of ECT on GABA levels. Nonetheless, the strength of the findings in the larger study 1 sample suggests that, unlike virtually all other biochemical indices, free plasma GABA may be reduced acutely after ECT. This acute decrease could reflect decreased levels of GABA in brain extracellular space or decreased brain turnover. In study 1, compared with ECT nonresponders, ECT responders had higher GABA levels at both baseline and after a course of ECT. Because plasma GABA levels are known to be low in a subset of patients with major depression, the higher GABA levels observed in clinical responders before and after the ECT course indirectly suggest that patients least abnormal in GABA levels may show superior clinical response. This also suggests that low plasma GABA is not a state marker for depression. PMID- 7796066 TI - Patient knowledge about electroconvulsive therapy: effect of an informational video. AB - We wished to ascertain whether the addition of an informational video to the informed consent procedure for electroconvulsive therapy (ECT) results in improved patient knowledge about ECT. Eighteen ECT patients were randomized to consent using the usual written document or using the written document and an informational video. The two groups were similar when compared on demographic variables and scores on the Brief Psychiatric Rating Scale (BPRS) and Mini-Mental State Examination (MMSE). Each subject, just after signing the informed consent document, was administered an 8-question ECT knowledge questionnaire. The addition of an informational video to the consent process for ECT did not result in improved knowledge about ECT. Poor knowledge about ECT might be accounted for by unsuccessful communication from the doctors or cognitive impairment and apathy on the part of the patients. One benefit of the video was increased interest from family members in ECT and the consent process. PMID- 7796067 TI - Radiographic screening for ECT: use and usefulness. AB - Members of the Association for Convulsive Therapy were surveyed by mail about use of muscle relaxants and radiologic studies for ECT. One hundred eleven completed responses were received (69%), indicating that 40% routinely acquire pre-ECT spine and skull radiographs taking from 1 to 10 films. From patients receiving more than one course of ECT, 57 pre- and post-ECT pairs of films taken within 1 month of the start and end of a course, respectively, were selected. The films were identified only by age and sex of the patient and were evaluated by a radiologist. A senior psychiatrist reviewed the pre-ECT radiographic reports to determine whether a change in routine ECT procedure was required. Few clinically significant radiologic findings in the pre- or post-ECT films were noted. PMID- 7796068 TI - ECT as a therapeutic option in severe brain injury. AB - Electroconvulsive therapy (ECT) is a safe, highly effective, and rapidly acting treatment for certain major psychiatric illnesses, most notably severe mood disorders. Disturbances in mood and behavior as symptoms of delirium may complicate recovery from traumatic brain injury, but virtually no data exist on the role of ECT as a treatment modality in such clinical situations. We describe a patient with severe, unremitting, agitated behavior following a severe closed head injury from a motor vehicle accident. The initial Glasgow Coma Scale score was 3, with computed tomographic evidence of bilateral frontal and left thalamic contusions. After awakening from a 21-day coma, the patient failed to improve beyond a Ranchos Los Amigos level 4 recovery stage. He exhibited persistent severe agitation with vocal outbursts and failed to assist in performing activities of daily living. His difficulties proved unresponsive to combined behavioral therapy and multiple trials of various psychopharmacologic agents. As an intervention of "last resort," he then received six brief-pulse, bilateral ECT treatments that resulted in marked lessening of his agitation and improvement in his ability to express his needs and participate in his self-care. Also, following the ECT, he showed a markedly enhanced response to psychopharmacologic agents. These findings may have important clinical implications for treatment of prolonged delirium after traumatic brain injury. PMID- 7796070 TI - Privileging for ECT. PMID- 7796069 TI - Generalized nonconvulsive status epilepticus after electroconvulsive therapy. AB - Status epilepticus is a rare complication of conventional single-stimulus electroconvulsive therapy (ECT). We report a case of ECT-induced nonconvulsive generalized status epilepticus (NGS) that lasted 3.5 days. The patient showed regressed psychotic behavior coupled with waxing and waning mutism and unresponsiveness as well as subtle unilateral motor signs. The diagnosis of NGS requires electroencephalographic confirmation. PMID- 7796071 TI - ECT: changing in Uruguay. PMID- 7796072 TI - Therapeutic use of fructose: professional freedom, 'pharmacovigilance' and Europe. PMID- 7796073 TI - Management and outcome of severe Guillain-Barre syndrome. AB - Seventy-nine patients with Guillain-Barre syndrome admitted to a neurological intensive therapy unit (ITU) between 1985 and 1992 were studied retrospectively. The mean age was 49.8 years (range 16-86) and the time between the first neurological symptom and admission to ITU was 10.2 days (0-62). Admission was precipitated by a combination of respiratory failure requiring ventilatory support (73.4%), bulbar weakness (57.0%), autonomic features (11.4%) and general medical factors (10.1%). Specific treatments included plasma exchange (65.8%), intravenous immunoglobulin (13.9%) and methylprednisolone/placebo (12.7%). Significant complications included lower respiratory tract infections (45.6%), hyponatraemia (25.3%), dysautonomia (19.0%), urinary tract infection (12.7%) and cognitive disturbances (8.9%). Four patients (5.1%) died during the acute illness. Duration of nadir correlated with duration of ventilation, duration of ITU stay and outcomes at 3 months, 6 months and 1 year. However, time to nadir, an indicator of rapidity of deterioration, did not correlate with any outcome. The low mortality in this series of acutely ill and severely disabled patients suggests that specialized intensive therapy units continue to have an important role in the management of acutely ill patients with Guillain-Barre syndrome. PMID- 7796075 TI - Insulin and C-peptide secretion in non-insulin-dependent diabetes mellitus and its response to dietary therapy. AB - We studied insulin and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) during standard oral or intravenous glucose tolerance tests (GTT) at the time of diagnosis and after 3 months dietary therapy. On the second occasion they also had an 'augmented' GTT, in which slow intravenous infusion of glucose raised basal plasma glucose to a level similar to that at the time of diagnosis. Eight patients had oral tests, and seven patients intravenous tests. In both groups, dietary therapy significantly reduced fasting and peak plasma glucose (p < 0.05 for oral; p < 0.01 for intravenous GTT). Serum insulin levels during conventional oral GTT were not significantly different after dietary therapy compared to diagnosis, but were significantly higher during the 'augmented' oral GTT (p < 0.05). In those patients who underwent intravenous GTT, there was a significant increase in both the total amount of insulin secreted (0 60 min) and in first-phase insulin secretion (0-10 min) during the 'augmented' test compared to diagnosis (p < 0.01), but first-phase insulin secretion during the conventional intravenous GTT was unchanged. Serum C-peptide responses were also greater during 'augmented' tests (p < 0.05), similar in pattern to serum insulin. There is a relative deficiency in insulin secretion in untreated NIDDM, which can be reversed by dietary therapy. It is essential to study insulin and C peptide secretion in controlled 'fasting' glucose conditions. PMID- 7796074 TI - Postural hypotension enhanced by exercise in patients with chronic autonomic failure. AB - The effect of supine exercise on blood pressure (BP), measured while recumbent and after head-up postural change, was investigated in three groups with marked postural hypotension due to chronic autonomic failure: 15 with associated neurological impairment (Shy-Drager syndrome, SDS, multiple system atrophy); 15 with pure autonomic failure (PAF) and two with a deficiency of the enzyme dopamine beta hydroxylase (DBH deficiency). Fifteen normal subjects were controls. In controls, exercise increased supine BP, and there was no postural fall before or after exercise. In SDS and PAF, however, exercise produced a substantial fall in BP, which was greater in PAF. In both groups, BP fell to a lower level on standing after than before exercise. In DBH deficiency, there was little change in BP with exercise, but BP fell to a lower level on standing after exercise. In all three groups with autonomic failure, there were more symptoms of postural hypotension on standing after exercise. The influence of exercise on both supine and postural BP, therefore, should be considered in the clinical and laboratory assessment of autonomic dysfunction. PMID- 7796076 TI - Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: the short synacthen versus the insulin tolerance test. AB - The short synacthen test (SST) is an effective method of assessing the hypothalamo-pituitary-adrenal (HPA) axis in patients with pituitary disease. Chronic glucocorticoid therapy may result in suppression of the HPA axis, and use of the SST has not been evaluated in these patients. This study compares the SST with the insulin tolerance test (ITT) in patients on long-term corticosteroid therapy. Both tests were done on 22 patients on long-term, stable-dose prednisolone (< 10 mg/day). A pass was defined as a 30 minute plasma cortisol > 550 nmol/l for the SST and a maximal cortisol of > 500 nmol/l for the ITT. Five patients passed both tests; nine failed both. Eight patients had discrepant results; all passed the ITT but failed the SST. There was a significant correlation (p < 0.001) between the maximum cortisol level achieved during the ITT and the 30 min SST value and the incremental rise. There was an inverse correlation between the dose and duration of use of steroids and the cortisol response during both tests. The SST is a reliable, safe and easily performed initial assessment of the HPA axis in patients on long-term corticosteroids. The ITT remains a valuable test for those who fail the SST. PMID- 7796077 TI - Bronchoalveolar lavage in pulmonary tuberculosis: a decision analysis approach. AB - We assessed the utility of bronchoalveolar lavage (BAL) in the diagnosis of pulmonary tuberculosis (PTB) in 50 consecutive HIV-negative patients with clinical and radiographic findings suggestive of PTB, but with negative microscopy for acid-fast bacilli (AFB) on sputum smear. Patients were grouped, using a scoring system, into relative likelihoods of having PTB (I-IV, in descending probability). Patients were started on anti-tuberculosis treatment according to the BAL results. Bacteriological diagnosis of PTB was confirmed in 22/50 BAL; 11 (91.6%), seven (37%) and four (40%) of groups I-III, respectively. In 13 cases, an early diagnosis of PTB was made by positive microscopy for AFB on BAL; an alternative diagnosis was made in six cases (bacterial pneumonia 4, carcinoma 2). A decision analysis model was created to assess the overall utility of BAL. This suggested that in a region of high PTB prevalence, and when the clinical diagnosis of PTB is likely, empirical treatment is the best course of action, with BAL being reserved for further investigation of non-responders. Early BAL should be considered when the diagnosis of PTB is uncertain. PMID- 7796078 TI - Fever as the presenting complaint of travellers returning from the tropics. AB - We investigated prospectively the cause of fever in patients requiring hospitalization after returning from the tropics. All consecutive admissions (n = 195) with oral temperature > 37.0 degrees C at the time of admission were enrolled. Final diagnosis as recorded on the discharge summary by the attending physician and results of any relevant laboratory or radiological investigations were recorded on standard proforma. Malaria accounted for 42% of admissions; two patients had returned to Britain more than 6 months before presentation. The second largest group was assumed to have a non-specific viral infection (25%). Cosmopolitan infections (urinary tract infection, community-acquired pneumonia, streptococcal sore throat, etc.) accounted for 9%. Coincidental infections (schistosomiasis, filariasis, intestinal helminths) were found in 16%. Serology was positive for HIV infection in 3%. The most useful investigation was a malaria film, which was positive in 45% of cases in which it was performed. The combination of thrombocytopaenia (platelet count < 100 x 10(9)) and hyperbilirubinaemia (bilirubin > 18 IU/ml) were useful predictive markers of malaria: all 23 patients with both abnormalities had positive malaria films. Malaria must be excluded in any febrile patient returning from the tropics. In the absence of a positive malaria film, the combination of a low platelet count and raised bilirubin may suggest the need for an empirical course of therapy. PMID- 7796079 TI - Perceptions, emotions and immunity: an integrated homeostatic network. PMID- 7796080 TI - Pathophysiology of hyperventilation. PMID- 7796081 TI - Lupus, C3 nephritic factor and partial lipodystrophy. PMID- 7796082 TI - Prospects for using a blood sample in the diagnosis of heart failure. PMID- 7796083 TI - Tamoxifen: oestrogen or anti-oestrogen in bone? PMID- 7796084 TI - Some determinants of whole-gut transit time: a population-based study. AB - Slow whole-gut transit time may be associated with an increased risk of gallstones, and possibly bowel cancer, but its determinants are unknown. We looked for these determinants in a community-based study of 884 women aged 25-69 years and 677 men aged 40-69 years. Transit time was estimated using prospective examination of three stools and a questionnaire about bowel habit. Diet and alcohol intake were assessed using a validated food frequency questionnaire. In women < 50 years not taking oral contraceptives, mean transit time was relatively constant across 10-year age bands (62 to 63 h). In older women it was also relatively constant, but was significantly shorter (58 to 59 h), suggesting an effect of female sex hormones. In women taking oral contraceptives, mean transit time was 6 h longer than in women of the same age not taking them (95% CI 1.4 to 10.6 h). In men drinking > 40 g alcohol/day, mean transit time was 49 h compared with 54 h in those drinking < 20 g/day (p < 0.0001). In alcohol-abstaining men, an effect of dietary NSP (non-starch polysaccharide or fibre) intake was clearly apparent. Alcohol consumption quickened transit in both sexes; oral contraceptive usage slowed it in women. Body mass index in both sexes, soluble NSP in men, and insoluble NSP in women also significantly and negatively affected transit time. The food groups which were related to transit time were potatoes and cooked fruit in men, and pulses and bread in women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796085 TI - Serodiagnosis of pericardial tuberculosis. AB - The AIDS epidemic has led to the resurgence of tuberculosis. Extrapulmonary manifestations may appear in over half of the patients who are dually infected. This has resulted in a rising incidence of tuberculous pericarditis in several parts of Africa such as Tanzania. We tested a solid-phase antibody competition sandwich ELISA (SACT-SE) as a potential means of diagnosing tuberculous pericarditis. Fifty-one African patients with clinically diagnosed tuberculous pericardial effusion (of whom 25 had confirmation by pericardial fluid culture) were tested using a monoclonal antibody (CDC/WHO ref. no. IT39) which was raised against a specific epitope on the Mycobacterium tuberculosis 30 kDa antigen. All but one patient had negative sputum microscopy for acid-fast bacilli. A sensitivity of 61% (at 96% specificity) was achieved. Sera from 25 African patients with smear-positive tuberculosis were also examined; of which 20 tested positive (sensitivity 80%). This is the largest study to date on the potential application of serology in diagnosing pericardial tuberculosis. PMID- 7796087 TI - QT dispersion in essential hypertension. AB - Increased QT dispersion is associated with sudden cardiac death in congestive heart failure, hypertrophic cardiomyopathy, and following acute myocardial infarction. Patients with hypertension, in particular those with left ventricular hypertrophy, are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with echo LVH. Sixty-nine untreated patients with essential hypertension had QT dispersion measured from a surface 12-lead electrocardiogram, and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness, and left ventricular internal diameter. Office blood pressure was recorded, and in 56 patients, 24 h ambulatory blood pressure monitoring was also done. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Similar findings were obtained when QT dispersion was corrected for heart rate (QTc dispersion). After patients with electrocardiographic left ventricular hypertrophy (n = 5) were excluded from the analysis, the above relationships persisted. Increased QT dispersion is thus found in those essential hypertensives at greatest risk of sudden death. Since this relationship persists even in the absence of electrocardiographic left ventricular hypertrophy, measurement of QT dispersion might be a simple, non invasive screening procedure to identify those hypertensives at greatest risk of sudden death. PMID- 7796088 TI - The haematologist as watchdog of community health by full blood count. AB - Although full blood counts (FBC) are among the most commonly performed laboratory tests, the contribution of routine FBCs to the diagnosis of new problems is controversial. This study represents a unique linkage of a consultant haematology team, reviewing all abnormal blood counts, to an organization providing ambulatory health care to 350,000 patients. The objective was to establish the underlying clinical disorders responsible for all abnormal FBCs during a 2-month period, and to estimate the impact of the haematology team on the diagnostic work up and management of newly identified problems. 572 (2.55%) of the 22,454 FBCs were abnormal. Of these, 357 showed microcytosis, caused by iron deficiency (58%), thalassaemia minor (35%), inflammation (6%) or chronic renal failure (1%). The most common causes of normocytic anaemia (25 patients) were disseminated malignancy and acute blood loss; of macrocytosis (27 patients), chronic liver disease and cancer; of erythrocytosis (16 patients), chronic hypoxia; of thrombocytopaenia (48 patients), chronic liver disease and ITP; of thrombocytosis (47 patients), iron deficiency and inflammation; of leukopaenia or pancytopaenia (20 patients), cirrhosis and disseminated malignancy; and of leukocytosis (26 patients), chronic leukaemias in the elderly and infection in children. Major new haematological abnormalities were encountered in 0.24% of all blood counts, representing about one new diagnosis per day. Routine blood counts do contribute to the health care of a population. Screening for haematological disease through a central clinical laboratory covering a large high-risk ambulatory population offers a cost-effective way of searching for serious clinical problems, alerting the primary physicians of their existence, and offering advice in continued evaluation and problem management. PMID- 7796086 TI - Lipoprotein(a) as a determinant of the severity of angiographically defined carotid atherosclerosis. AB - We measured fasting serum lipids, lipoproteins, apolipoproteins and lipoprotein(a) [Lp(a)] in 49 Caucasian patients with transient ischaemic attacks undergoing carotid angiography. The severity of extracranial cerebrovascular disease was assessed visually by a highly reproducible grading system that focused on the internal carotid artery and carotid bifurcation. Compared with a healthy reference group, patients had significantly higher serum concentrations of: total cholesterol (mean +/- SD), 6.2 +/- 1.6 vs. 5.6 +/- 1.0 mmol/l, p = 0.02; apolipoprotein B, 1.4 +/- 0.5 vs. 1.2 +/- 0.3 g/l, p = 0.03; triglyceride [geometric mean(95% CI)], 2.02(1.75-2.32) vs. 1.66(0.67-4.06) mmol/l, p = 0.03; and Lp(a), 0.33(0.26-0.42) vs. 0.17(0.40-0.76) g/l, p < 0.001. Regression analysis showed that of the lipoprotein-related variables, only Lp(a) was significantly related to the severity of carotid artery disease (p = 0.04) in the patients; this association remained significant after adjusting for age, sex, blood pressure, and a history of stroke. Serum Lp(a) concentration was significantly higher in patients with carotid artery disease severity score above the median value of the sample population compared with those below the median: 0.45 vs. 0.24 g/l (95% CI for difference 0.35-0.88), p = 0.01. Elevated serum Lp(a) is a significant determinant of the extent of carotid atherosclerosis and may be useful in identifying patients most at risk of stroke. PMID- 7796090 TI - Critical illness poly-neuropathy following severe hyperpyrexia. AB - Two patients developed critical illness polyneuropathy after severe hyperpyrexia. Fever was secondary to a phaeochromocytoma in one patient and sepsis in the other. These observations suggest that high fever may be one possible aetiology of critical illness polyneuropathy. PMID- 7796089 TI - Pharmacokinetics and pharmacodynamics of dichloroacetate in children with lactic acidosis due to severe malaria. AB - Lactic acidosis frequently complicates severe malaria in African children, and is a strong independent predictor of mortality. We tested the hypothesis that sodium dichloroacetate (DCA), an activator of pyruvate dehydrogenase, rapidly reduces hyperlactataemia in this patient population. Eighteen children with severe malaria and capillary plasma lactate > or = 5 mM were randomized to receive either intramuscular quinine plus a single 50 mg/kg intravenous infusion of DCA in saline, or quinine plus intravenous saline alone. Two patients in each treatment group died following randomization. Thirty minutes after treatment, the mean plasma lactate was 28% below pretreatment baseline values in the DCA group, but was unchanged in the placebo group. Throughout the first 4 h after treatment, mean plasma lactate in the DCA-treated patients was significantly less than that in controls (p = 0.003). Thereafter, mean plasma lactate declined in both groups and was < 2 mM 10 h after treatment. DCA was well tolerated and did not alter quinine pharmacokinetics. A single intravenous dose of DCA rapidly improved lactic acidosis in African children with severe malaria, suggesting that DCA may be a useful adjunct in the initial treatment of these patients, and may increase their chance of survival by improving a major complication of their illness. PMID- 7796091 TI - Does folic acid harm people with vitamin B12 deficiency? AB - Oral folic acid given before and during pregnancy can prevent about 75% of fetal neural tube defects. Even in large dose (20 mg daily) folic acid has never been shown to harm normal people, but it has acquired a bad reputation in pernicious anaemia. Before 1930, if untreated patients survived the anaemia, they succumbed to peripheral neuritis, subacute combined degeneration of the spinal cord, and death. The speed of this progression was extremely variable. From 1947 onwards, there were many reports of rapid neurological deterioration during administration of folic acid as sole therapy to people with pernicious anaemia. However, a review of clinical studies published before the introduction of liver and vitamin B12 therapy shows that neurological deterioration was often quite as rapid and severe in untreated patients. Oral folic acid can usually correct or prevent the anaemia of pernicious anaemia. Thus it could mask the underlying disease, and allow the development or progression of neurological deterioration, if diagnosis depended on the presence of anaemic symptoms. This possibility can readily be overcome by adequate education of doctors, so that a macrocytic anaemia is not regarded as a necessary accompanying sign of the neurological disorder. The hypothetical and avoidable side-effects of food fortification with folic acid have to be balanced against the certain benefit of preventing neural tube defects in unplanned pregnancies, and also against the probability that adults may be spared the neuropsychiatric and other ill-effects which result from inadequate dietary folic acid. PMID- 7796092 TI - A Golgi and horseradish peroxidase study of the sonic motor nucleus of the oyster toadfish. AB - The sonic motor nucleus (SMN) of the oyster toadfish Opsanus tau, a single midline structure in the occipital spinal cord and caudal medulla, contains large electrically-coupled motoneurons. Although interpretation is complicated by multiyear growth in soma size, neurons in males may be either large (L) or small (S), whereas females have exclusively S neurons. Golgi stains have allowed separation of five neuron variants (rostral, dorsal, stellate, ventral and caudal) which differ in location, soma shape and size, and direction and pattern of dendritic branching. All variants are present in L and S males and in females, and retrograde transport of horseradish peroxidase indicates that all variants are motoneurons. The SMN is organized into three horizontal layers with rostral and dorsal neurons forming a rostrocaudally arrayed network across the dorsal dorsolateral surface. Stellate cells are found in the middle layer, and ventral cells with laterally directed dendrites that exit the SMN line the inferior surface. Caudal neurons with caudally directed exiting dendrites are arranged in parallel rows in the caudal fifth of the SMN. We suggest that variant differences in dendritic orientation relate to different patterns of innervation by multiple afferents to the SMN and function to maximize contacts between neurons as a means of facilitating synchronization within the nucleus. Sexual dimorphism has been demonstrated to a minor degree: all variants have larger somas in L fish than S fish, but no difference has been found in primary dendrite diameter. Larger somas would potentially support the greater amount of sound production by nesting males who produce a mating boatwhistle call. Equivalent dendrite diameter in females, who are just as likely as males to grunt, an agonistic call, suggests that female Opsanus have a well developed sonic circuitry compared to Porichthys, another toadfish in which females are typically silent. PMID- 7796093 TI - Development of the visual cortex in a wallaby--phylogenetic implications. AB - The visual cortex of one of the smallest macropod marsupials, a wallaby, the quokka Setonix brachyurus, was examined at maturity and during development from postnatal day 1 to 150 in Nissl-stained or Golgi-stained sections. Injections of horseradish peroxidase into the primary visual centres in adults identified cortical neurons projecting to these regions. The pattern of cell generation was determined by tritiated thymidine/autoradiography. The adult visual cortex was composed of the usual six layers of cells with dendritic morphologies similar to those seen in eutherian (placental) mammals. The margin of Layer 6 overlapped slightly with the white matter, and pyramidal cells projecting to subcortical regions were located at all depths of Layer 6. Cortical development was similar to that of eutherian mammals, with the formation of transient cellular layers below the developing cortical plate. Autoradiographic studies confirmed that the cortical plate was composed of two layers: a compact zone of densely packed cells located pial to a striated layer containing more loosely packed cells. Postnatal cell generation of Layers 6-2 took place from postnatal day 3 to day 85, with Layer 4 neurons, the main target of incoming visual axons, being generated around postnatal day 40. Cells located at maturity in the white matter, mostly of glial morphology, were generated from postnatal day 40. A subplate zone containing early differentiating cells was not evident, and postnatal 3H-thymidine labelling did not identify a population of early generated neurons below the cortical plate. In the tammar wallaby Macropus eugenii, the majority of target neurons for incoming geniculate axons are generated about 20 days after the first axons enter directly into the cortical plate without a waiting period in a subplate. Geniculate axons in the wallabies have a relatively longer 'wait' for their target neurons than do those in cats or monkeys. Therefore, if geniculate axons in marsupials make temporary synapses, while they wait for their target neurons to be generated, their temporary connections must, unlike those in cats or monkeys, be with cells already in the cortical plate. PMID- 7796095 TI - Anthony H.M. Lohman: reflections on a distinguished career in anatomy. PMID- 7796094 TI - Localization of met-enkephalin and vasoactive intestinal polypeptide in the brains of male zebra finches. AB - An interconnected series of brain nuclei controls song learning and behavior in male zebra finches (Poephila guttata). This study examined the distribution of fibers, terminals, and somata immunoreactive for two neuropeptides, methionine enkephalin (ENK) and vasoactive intestinal polypeptide (VIP), in song-control nuclei of adult males. In addition, the broad pattern of major regions of labeling throughout the forebrain and midbrain was determined. The telencephalic song-control nuclei MAN (magnocellular nucleus of the anterior neostriatum), Area X of the striatum, HVC (higher vocal center), and RA (robust nucleus of the archistriatum) contained abundant ENK immunoreactivity, including labeled fibers and somata. In addition, intensely labeled fibers and terminals were seen in the thalamic nucleus DLM (medial portion of the dorsolateral nucleus of the anterior thalamus). High levels of VIP immunoreactivity were also seen in MAN, HVC, and RA, but this label consisted of fiber and terminals only. Area X and surrounding striatum contained extremely sparsely distributed VIP-labeled processes. Somata positive for VIP were not seen throughout cortical regions such as the neostriatum and hyperstriatum but were abundant in the lateral striatum (paleostriatum augmentatum, PA) and may contribute to a dense field of terminal labeling seen in the globus pallidus. The apparent presence of a robust VIP positive striato-pallidal projection is not typical of major basal ganglia pathways in vertebrates, raising the possibility that passerine birds have diverged from the typical amniote pattern. PMID- 7796096 TI - Co-localization of aromatase enzyme and estrogen receptor immunoreactivity in the preoptic area during reproductive aging. AB - Immunoreactive aromatase enzyme (AROM-IR) was studied in the preoptic and septal ares of the male Japanese quail brain relative to the age-related decline in endocrine and behavioral components of reproduction. Additional analyses were conducted to determine if the co-localization of AROM-IR and estrogen receptor immunoreactivity (ER-IR) in the medial preoptic area change during aging. Young, sexually active, male quail (6 months of age) were compared to aged sexually active or inactive, male quail (36 months of age). Testis size decreased in old, sexually inactive males, similar to our previous observations. The numbers of AROM-IR neurons in the medial preoptic area (POM) and the lateral septum (LS) decreased significantly with aging and sexual activity. The number of cells that co-localized both AROM-IR and ER-IR did not differ with age. As a consequence of the age-related change in AROM-IR cells, the relative percentage of dual labelled (AROM-IR and ER-IR) and single labelled cells (AROM-IR) increased in aged males. These data provide histochemical evidence that alterations in the aromatase enzyme system in the medial preoptic area may underlie behavioral and endocrine events associated with reproductive aging. PMID- 7796097 TI - Delayed increase of tyrosine hydroxylation in the rat A2 medullary neurons upon long-term hypoxia. AB - In vivo and in vitro activity of tyrosine hydroxylase (TH) was estimated in the catecholaminergic A2 cell group of the nucleus tractus solitarius (NTS) in rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 2 h, 3, 7, 14 or 21 days. The A2 cell group was subdivided into two subgroups. In the caudal A2 subgroup located caudal to the calamus scriptorius, long-term but not acute hypoxia elicited an increase of in vivo tyrosine hydroxylation rate after 7 days of exposure (+60% above normoxic controls). The increase of in vivo TH activity was maintained at the same level at the end of hypoxic exposure. In vitro TH activity was increased transiently after 7 days of hypoxia (+92% above normoxic (controls). In thr rostral A2 subgroup, hypoxia elicited a significant increase of in vivo tyrosine hydroxylation at 7 days (+38%) but did not alter in vitro TH activity throughout the whole exposure. Hypoxia produced no detectable change in TH activity in other noradrenergic cell groups of the brain stem (locus coeruleus, A5) except for a transient inhibition of in vivo TH activity in A5 after 2 h. Immunocytochemical analyses confirmed that the catecholaminergic neurons in the caudal A2 area are not only of a noradrenergic nature. The neurons were located in the commissural subnucleus of the NTS. On the other hand, the rostral A2 area contains noradrenergic neurons intermingled with a small number of adrenergic cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796098 TI - [3H]GBR 12935 labels mainly the piperazine acceptor site in the rat prefrontal cortex. AB - The binding characteristics of [3H]GBR 12935, a ligand for the dopamine (DA) transporter, have been extensively investigated in the striatum. The present study was designed to characterize [3H]GBR 12935-binding to prefrontal cortex (PFC) in rats. This region receives a dense DA input from the ventral tegmental area and is suspected to play a major role in higher associative functions. We demonstrated high-affinity, saturable, mazindol-sensitive [3H]GBR 12935-binding in the rat PFC; however, in contrast to the striatum, such binding was inhibited by increasing concentrations of Na+. This fact, together with the irregular pattern of the association kinetics and the marked sensitivity of [3H]GBR 12935 binding to piperazine derivatives, indicates the possible presence of more than one [3H]GBR 12935-binding site in the PFC. Furthermore, it appears that [3H] 12935 in the rat PFC labels mainly 'the piperazine acceptor site' and not the DA transporter. PMID- 7796099 TI - Indomethacin reduces both Krox-24 expression in the rat lumbar spinal cord and inflammatory signs following intraplantar carrageenan. AB - This study evaluated the 'evoked' expression of Krox-24 protein in the lumbar spinal cord after peripheral carrageenan-induced inflammation and its modification by preadministration of indomethacin, a non-steroidal anti inflammatory drug, in freely moving rats. Three h after intraplantar carrageenan (6 mg/150 microliters saline) a maximal 'evoked' Krox-24 expression was observed in L2-L6 segments of the dorsal horn ipsilateral to carrageenan inflammation. A maximal number of 'evoked' Krox-24 neurons was observed in L4-L5 segments, predominantly in the superficial laminae (I-II) and to a lesser extent in the medial part of neck (laminae V-VI) of the dorsal horn. Such an increase was not observed after an intraplantar injection of control vehicle saline. increase doses of carrageenan (1, 3 and 6 mg) induced a dose-dependent increase (r2 = 0.617, P < 0.0001) in the number of evoked' Krox-24 neurons observed in the superficial dorsal horn 3 h after carrageenan. Systemic preadministration of indomethacin (1, 2.5 and 5 mg/kg) dose-dependently reduced (r2 = 0.508, P < 0.0001) the total number of carrageenan (6 mg at 3 h)-'evoked' Krox-24 neurons (29 +/- 5, 45 +/- 4 and 57 +/- 2% reduction as compared with control, respectively). Systemic indomethacin dose-dependently reduced the inflamed paw and ankle diameter (16 +/- 8, 34 +/- 12, 54 +/- 6% and 48 +/- 14,. 75 + 16, 90 +/ 7% reduction as compared with the control carrageenan inflammation, respectively). There was a positive correlation between the effect of systemic indomethacin on both 'evoked' Krox-24 expression in superficial laminae and the inflammatory signs (r2 = 0.25, P < 0.01 for the paw diameter; r2 = 0.22, P < 0.05 for the ankle diameter). In addition, the total number of 'evoked' Krox-24 neurons was significantly reduced (43 +/- 5% reduction as compared with control) by an oral pretreatment of indomethacin (10 + 10 mg/kg). Oral indomethacin totally blocked the ankle diameter and reduced the paw diameter (100 + 14 and 30 +/- 6% reduction of the control carrageenan inflammation, respectively). PMID- 7796100 TI - The role of the medial prefrontal cortex of rats in short-term memory functioning: further support for involvement of cholinergic, rather than dopaminergic mechanisms. AB - The putative involvement of the dopaminergic innervation of the medial part of the prefrontal cortex (PFC) in short-term memory functioning was investigated by evaluating the effects of local infusions of dopaminergic drugs into the ventral part of the medial PFC of rats in an operant delayed-matching-to-position (DMTP) task. Two separate groups of rats were tested after bilateral microinfusion of several doses of either the dopamine receptor agonist apomorphine (APO) or the dopamine receptor antagonist cis-flupenthixol (FLU) into the ventromedial PFC. In addition, all animals were tested after infusion of several doses of the muscarinic receptor antagonist scopolamine (SCO) and the dopamine DI receptor antagonist SCH-23390 (SCH). The drugs tested affected DMTP performance differentially. APO had no effect on response accuracy, although it dose dependently affected nose poke activity and response latencies. FLU and SCH both induced a dose-dependent, but delay-independent deterioration of response accuracy that was paralleled by increases in response latencies and decreases in nose poke frequencies, causing some animals to stop responding after infusion of the highest doses of both drugs. In contrast, SCO infusions into the ventromedial PFC induced a dose- and delay-dependent deterioration of response accuracy, that was accompanied by an increase in response latencies only. Taken together, these results provide additional support for the involvement of cholinergic, rather than dopaminergic mechanisms in short-term memory supported by the medial PFC of the rat, and they are not in favor of a functional dissociation between the dorsomedial PFC and the ventromedial PFC in the role. PMID- 7796101 TI - Olfactory bulb glycogen metabolism: noradrenergic modulation in the young rat. AB - The olfactory bulb exhibits high glycogen phosphorylase activity, the rate limiting enzyme in the mobilization of glycogen. The bulb also receives dense noradrenergic innervation and noradrenaline is known to stimulate glycogen breakdown. We determined the levels of glycogen in the bulb over the course of development and then determined the ability of noradrenaline to mobilize bulb glycogen. At birth, olfactory bulbs have very high levels of glycogen, with levels declining as the pups develop. Picomolar levels of noradrenaline mobilize glycogen in the bulb,. Initially, beta-adrenergic receptors mediate teh glycogenolysis and subsequently, the alpha-noradrenergic receptors in the bulb stimulate the breakdown of glycogen. Carnosine is involved in the repletion of bulb glycogen levels. The stimulation of glycogen breakdown by noradrenaline may play a role in allowing the increased activity that accompanies early olfactory stimulation. PMID- 7796102 TI - Subtype-specificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat. AB - In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective alpha 2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the alpha 2AD antagonist BRL 44408 or the alpha 2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 4408 caused a significant increase of the extracellular level of NF. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation evoked release of [3H]NE was determined. The alpha 2-antagonists were applied in a concentration range of 10(-8) to 10(-6) M, ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments, BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different alpha 2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P < 0.0001) in hippocampus and frontal cortex have the alpha 2 adrenoceptors have been characterized as alpha 2d-subtype. Our data indicate that hippocampal NE release in rat is regulated by alpha 2D-adrenoceptors, a species variation of the human alpha 2A-subtype. PMID- 7796103 TI - Olfactory experience modulated apoptosis in the developing olfactory bulb. AB - Early sensory stimulation plays a key role in shaping the structure and function of the developing olfactory system. Here, we provide the first direct evidence for apoptotic cell death in the olfactory bulbs of rat pups during normal development and we also demonstrate that olfactory deprivation by unilateral naris occlusion causes a dramatic increase in apoptotic cell death in the glomerular and granule cell layers of the deprived bulb. The accessory olfactory bulbs displayed a remarkably high basal level of apoptosis but the occluded accessory bulb did not differ in that regard from the control accessory bulb. These results suggest that apoptosis may be an important mechanism by which the olfactory system can adjust its cell numbers in response in sensory stimuli experienced in early life, thereby underlying one form of plasticity in the developing olfactory system. PMID- 7796104 TI - Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21. AB - The ability of two synthetic nicotine receptor ligands, TGS-21 and DMAB, to chronically enhance the cognitive function of aged rats was evaluated in three diverse tasks and compared to the cognition-enhancing effects of nicotine administration. 15 min prior to daily behavioral testing, aged 22-24 month old rats received an i.p. injection of nicotine (.02 mg/kg), GTS-21 (1 mg/kg), DMAB (2mg/kg), or saline vehicle and were tested in either one-way active avoidance pole jumping, Lashley III maze, or a 17-arm radial maze. GTS-21 pretreatment was as effective as nicotine for enhancing the acquisition of aged rats in both one way active avoidance and Lashley III maze training. In 17-arm radial maze testing, GTS-21 improved both general learning and reference (long-term) memory to the same extent as nicotine. Although DMAB pretreatment enhanced reference memory in 17-arm radial maze testing to the same as nicotine, it did not affect general learning in this complex task and did not exert any cognition-enhancing effects in Lashley III maze training. These results indicate that GTS-21 has cognition-enhancing abilities in aged rats that are comparable to those of nicotine in a variety of behavioral tasks. Since GTS-21 acts preferentially on brain nicotinic receptors and is less toxic than nicotine, thses results further indicate that GTS-21 may have substantive therapeutic value in the treatment of age-associated memory impairment (AAMI) and/or Alzheimer's disease. PMID- 7796105 TI - Enhanced restoration of striatal dopamine concentrations by combined GM1 ganglioside and neurotrophic factor treatments. AB - Intraperitoneal injection of GM1 ganglioside or intracerebroventricular infusion of basic fibroblast growth factor (FGF-2) or epidermal growth factor (EGF) partially restored dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum of young MPTP-treated mice. Combined treatments of GM1 ganglioside with FGF-2 or EGF produced a greater restoration of striatal dopamine levels than treatments with GM1 or either of the neurotrophic factors alone. GM1 treatment, but not trophic factor treatments caused significant sparing of substantia nigra pars compacta (SNc) tyrosine hydroxylase (TH)-positive neurons. These results confirm previous findings that GM1 provides trophic support for damaged dopamine neurons and suggests that GM1, FGF-2, and EGF may also enhance dopaminergic function in residual neurons. The results also suggest that a potentially fruitful approach to treating degenerative disorders of the dopamine system may be the use of combined trophic factor therapies. PMID- 7796106 TI - c-fos immunoreactivity in the brain following electrical or chemical stimulation of the medial hypothalamus of freely moving rats. AB - c-fos immunoreactivity was used to map brain areas in which neurons reacted either to electrical stimulation or to microinjection of the excitatory amino acid kainate and of the GABAA antagonist, SR-95531, applied to the medial hypothalamus of freely moving rats. All these stimulations induced flight behavior of moderate intensity. Immunoreactive cells were found within a radius of 0.5 mm around the stimulated area. Distally, clusters of labeled cells were found ipsilaterally in the piriform and entorhinal cortices, in several amygdaloid nuclei, in the bed nucleus of the stria terminalis, in the septo hypothalamic nucleus, in the paraventricular, anterior and dorsomedial hypothalamic nuclei, the the paraventricular thalamic nucleus, in the dorsal periaqueductal gray extending to the cuneiform nucleus, and bilaterally in the supramammillary decussation and the locus coeruleus. The specificity of the brain areas thus labeled was indicated by the unilateral pattern of activation as well as by the different pattern obtained after control microinjection of saline. Therefore, these results are likely to provide sound information about the brain structures involved in defensive-aversive behavior evoked from the medial hypothalamus. PMID- 7796107 TI - A retrograde double-labelling study of retinal ganglion cells that project ipsilaterally to vLGN and LPN rather than dLGN and SC, in albino rat. AB - We studied ipsilaterally projecting, double-labeled retinal ganglion cells that have bifurcating axons by retrograde fluorescent double-labeling in albino rats. Ten albino (Wistar, Japan Ceca) rats of either sex, weighing 350-400 g were used. With the rats in a state of deep anesthesia, we pressure-injected 0.02 microliter of 15% Evans blue (EB) into the right ventral lateral geniculate nucleus (vLGN), and 4% Fluoro-gold (FG) iontophoretically into the right posterior lateral thalamic nucleus (LP). The animals were perfused with formol-saline 48-72 h later and both the brain and eyes were exercised. The brain was sectioned coronally, and each retina was removed and mounted flat on a glass slide. Double-labeled cells were found in the ventral temporal crescent of the retina. In one animal and total number of ipsilaterally labeled cells was 566, and the percentage of double-labeled vLGN and LP projecting cells, single-labeled vLGN projecting cells, and single-labeled LP projecting cells were 29.8, 58.8 and 11.3, respectively. PMID- 7796108 TI - Phase-dependent phase shift of methamphetamine-induced circadian rhythm by haloperidol in SCN-lesioned rats. AB - Haloperidol, a non-selective dopamine receptor antagonist, was injected intraperitoneally in to suprachiasmatic nucleus (SCN)-lesioned rats at various phases of the locomotor activity rhythm induced by methamphetamine (MAP) treatment. A single injection of haloperidol shifted the phase of MAP-induced locomotor rhythm phase dependently, while saline injection had no effect on the phase. A phase-response curve of MAP-induced rhythm for haloperidol had a small phase-advancing area at CT 13 to 15, a large phase-delaying area at CT 3 to 7 and a dead zone at CT 17 to 1. Although the day-to-day variation of MAP-induced locomotor rhythm was about 2.5-times as great as that of light entrainable circadian rhythm, the phase shifts of both directions were statistically significant. Phase delay shifts at CT 5 depended on the dose of haloperidol. In addition to the phase-shifting effect, haloperidol suppressed the MAP-induced locomotor activity for activity for about 10 h regardless of the phase of the injection. Pentobarbital also suppressed ther locomotor activity for a similar duration. However, significant phase shift was not detected with pentobarbital injected at CT 5 or CT 13, at the phase where haloperidol induced the maximal phase delay or advance, respectively. Present findings suggest that the dopaminergic mechanism is involved in the entrainment and/or oscillatory mechanism of the MAP-induced rhythm. PMID- 7796109 TI - Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine. AB - The acute psychomotor response (rotational behavior in rats with a unilateral 6 OHDA lesion), and the development of sensitization, were studied in rats that received seven consecutive daily injections of amphetamine (Experiment 1) or cocaine (Experiment 2) either at home or in a 'novel' test environment. The home (HOME) and novel (NOVEL) cages were physically identical, but one group lived and was tested in these cages, whereas the rats in the other group were transported from the stainless steel hanging cages where they lived, to those NOVEl test cages, for each test session. In Exp. 1, the acute psychomotor response to 3.0 mg/kg of amphetamine i.p. and the development of sensitization (increase in the rotational response between the first and the the seventh test session) were greater in the NOVEL than in the HOME environment. In Expt. 2, there were no significant group differences in the acute response to 20 mg/kg of cocaine i.p., but the animals tested in the NOVEL environment showed greater sensitization than animals tested in the HOME environment. In addition, the animals pretreated with cocaine in the NOVEL environment, but not those pretreated with cocaine in the HOME environment, showed conditioned rotational behavior in response to an injection of saline. These data indicate that: (i) sensitization to the psychomotor activating effects of both amphetamine and cocaine is enhanced in a NOVEL environment; (ii) this phenomenon appears to the independent of the effects of the NOVEL environment on the acute response to these drugs; (iii) a robust conditioned psychomotor response to contextual cues develops only when cocaine treatments are given in the NOVEL test environment. PMID- 7796110 TI - Behavioral sensitization to cocaine: modulation by the cyclic AMP system in the nucleus accumbens. AB - We have previously observed that chronic cocaine administration increases levels of adenylyl cyclase and cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAc). In the present work we directly examined the involvement of the cAMP system at the level of the NAc in cocaine-induced locomotor activity and sensitization. Groups of rats were pretreated on 3 consecutive days with cocaine (10 mg/kg, i.p.) concurrently with intraacumbens infusion saline, 8-bromo-cAMP (2 micrograms/side; a membrane permanent analogue of cAMP which activates PKA), or RP-CPT-cAMP (20 nmol/side; which inhibits PKA). In a separate experiment, control animals received total infusion of either 8-bromo-cAMP or saline plus i.p. saline. All animals were tested for locomotor activity on pretreatment days, and following an additional cocaine challenge ona subsequent day. Over pretreatment days, animals given 8-bromo-cAMP showed greater cocaine-induced activity, while animals given RP-CPT-cAMP tended to be less active, compared to saline infused animals. When subsequently challenged with cocaine, animals pretreated with intraaccumbens 8-bromo-cAMP showed greater locomotor activity during the last 30 min of the 60 min test session than animals pretreated with saline or RP-CRT cAMP. No differences in locomotor activity were evident between the two control groups on pretreatment or challenge days. These data suggest that PKA activation at the level of the NAc may have a facilitative role with respect to acute and long-term stimulant-induced locomotor activity. PMID- 7796111 TI - Widespread and lateralization effects of acute traumatic brain injury on norepinephrine turnover in the rat brain. AB - Norepinephrine (NE) has been implicated in recovery of function following traumatic brain injury (TBI). While bilateral decrease in brain NE turnover occur at 6-24 h after TBI, it is unknown what effects unilateral TBI might have on brain NE turnover the first few minutes after injury. Her male Sprague-Dawley rats had unilateral confusions of either the right or left somatosensory cortex produced by an air between piston. At 30 min after TBI, brain NE turnover was assessed by measuring the ratio of 3-methoxy-4 hydroxyphenylglycol (MHPG) to NE levels in various brain regions. Both right and left TBI produced 32-103% increases in NE turnover at the injury site and in the ipsilateral cerebral cortex surrounding, rostral and caudal to the injury as compared to the contralateral, uninjured site or to the homologous sites in uninjured controls. NE turnover was also altered selectively in some brain areas not affected by right TBI. Left TBI decreased NE turnover by 29% in the frontal cortex contralateral to the injury and by 24% bilaterally in the hypothalamus while increasing locus coeruleus NE turnover by 72% compared to uninjured controls. Thus, unilateral cortical TBI produced predominantly ipsilateral increases in cortical NE turnover but variable, bilateral changes in NE turnover in subcortical areas which were dependent upon the side of injury. These subcortical differences may explain some of the lateralized effects of cortical injury on post-injury behavior. PMID- 7796112 TI - The role of extracellular ionic changes in upregulating the mRNA for glial fibrillary acidic protein following spreading depression. AB - While spreading depression has been shown to be a powerful stimulus in upregulating glial fibrillary acidic protein (GFAP) mRNA expression, the specific physiological signal underlying the upregulation is unknown. During spreading depression, extracellular ionic concentrations are altered markedly. The present study evaluates the role of these changes in extracellular ionic concentrations as potential signals influencing GFAP mRNA expression. Gel foam pledgets saturated with artificial cerebrospinal fluid (CSF) solutions in which [Na+], [Ca2+], [K+] and [H+] were altered one at a time to match concentrations seen in spreading depression were applied to exposed parietal cortex for one hour. Dot and in situ hybridization techniques were used to evaluate GFAP mRNA levels. We found that CSF containing 60 mM KCl produced a dramatic upregulation of GFAP mRNA levels throughout the cerebral cortex of the ipsilateral hemisphere without causing detectable tissue damage. The pattern and time course of the change were similar to those following application of 3 M KCl. Alteration of other ionic species did not affect GFAP mRNA levels. However, the upregulation of GFAP mRNA was not likely due directly to the increased [K+], but rather to the spreading depression that the elevated [K+] induced. This was demonstrated by the finding that the upregulation in GFAP mRNA induced by the potassium exposure was totally blocked by prior administration of MK-801, an NMDA antagonist that blocks spreading depression. These results demonstrate that an upregulation in GFAP mRNA can occur in the absence of degeneration debris and that the initiating events can be related to physiological changes, but that changes in extracellular ionic concentrations are not the likely molecular signals underlying the upregulation. PMID- 7796113 TI - Spinoparabrachial tract neurons showing substance P receptor-like immunoreactivity in the lumbar spinal cord of the rat. AB - By using substance P receptor (SPR) immunofluorescence histochemistry combined with fluorescent retrograde labeling, SPR-like immunoreactive (SPR-LI) neurons sending their axons to the lateral parabrachial region were observed in the lumbar spinal cord of the rat. After injection of Fluoro-Gold into the lateral parabrachial region, retrogradely labeled neurons with SPR-LI were seen frequently in lamina I and the lateral spinal nucleus, and occasionally in laminae IV and V, with a predominantly contralateral distribution. Some of these neurons, especially those in lamina I, may convey nociceptive information to the lateral parabrachial region. PMID- 7796115 TI - Calretinin-immunoreactive neurons in the human striatum. AB - The human striatum contains two types of neurons displaying immunoreactivity for the calcium-binding protein calretinin (CR): (1) large (22, 44 microns>), multipolar neurons with 5-7 long, aspiny and tightly branched dendrites, and (2) medium-sized (9-18 microns), round-to-oval neurons with 2-3 long, varicose and poorly branched dendrites. These CR neurons represent only a small proportion of the total neuronal population and they are heterogeneously distributed in the striatum. The large CR neurons are more numerous in the putamen than in the caudate nucleus, whereas the inverse is true for the medium-sized CR neurons. The ratio of large- to medium-size CR neurons is 1:4 in the putamen compared to 1:6 in the caudate nucleus. The existence of these two distinct subsets of chemospecific striatal neurons suggest that CR may play an important role in the intrinsic organization of the human striatum. PMID- 7796114 TI - Complete cerebral ischemia with short-term survival in rat induced by cardiac arrest. II. Extracellular and intracellular accumulation of apolipoproteins E and J in the brain. AB - The distribution of apolipoprotein E (apo E) and apolipoprotein J (apo J) was investigated immunocytochemically in rats at various time intervals after 10 min global cerebral ischemia (GCI) induced by cardiac arrest. Strong apo E and weaker apo J immunoreactivity was found extracellularly in multiple deposits located close to the microvessels. These deposits appeared 3 h after GCI and were present, but not in all the animals, at all time intervals studied post-GCL. In some rats, apo E immunoreactivity was also found in small necrotic foci. Widespread, neuronal apo E immunostaining appeared 6 h post-GCI. However, the strongest neuronal apo E immunoreactivity was found 7 days post-GCI in those neurons, most often observed in the CA1 hippocampal region, exhibiting signs of ischemic cell damage. These ischemically damaged neurons displayed weaker immunoreactivity to apo J, despite its increase in the response to GCI in the various brain regions examined. Our data show that mechanisms operating in ischemia are able to supply large amounts of apo E and apo J to the brain tissue and suggest involvement of both apo E and apo J in a complex series of events occurring in the ischemic brain. Perivascular deposits of apo E/apo J colocalized with amyloid beta protein precursor epitopes that have been disclosed by us previously in this model. Whether this phenomenon is limited to postischemic brain tissue, or can be encountered also in other pathological conditions will require further elaboration. PMID- 7796116 TI - Increases in NMDA receptor binding are specifically related to memory formation for a passive avoidance task in the chick: a quantitative autoradiographic study. AB - One-day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance task in which the aversive stimulus was an unpleasant lasting substance, methylanthranilate (MeA). Control birds were presented with a water (W) coated bead. Five minutes after training a group of McA-trained chicks were given a brief sub-convulsive trans-cranial electric shock, which rendered half amnesic whilst the remainder were able to show recall for the aversive stimulus. Thirty minutes after training birds were killed and quantitative receptor autoradiography was used to determine NMDA sensitive [3H]L-glutamate binding in specific regions of the forebrain of: (i) MeA-trained chicks; (ii) water-control chicks; (iii) MeA-trained electroshocked chicks showing recall; and (iv) MeA electroshocked chicks amnesic for the aversive stimulus. Increases (805 in the left lobus parolfactorius and 67% in the left intermediate medial hyperstriatum ventrale) in NMDA sensitive [3H]L-glutamate binding occurred in electro-shocked chicks which showed recall of the aversive experience but were absent in MeA trained chicks rendered amnesic by electro-shock. The increased binding in electroshocked MeA-trained birds which showed recall was similar to that observed previously in MeA-trained birds (without electroshock), compared to water control birds, whereas binding levels in McA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly in MeA trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly that alterations in binding to glutamate receptor sub-types are specific to memory formation for the passive avoidance task. PMID- 7796118 TI - Suppression of interleukin-1 beta production in the circumventricular organs in endotoxin-tolerant rabbits. AB - Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits which show febrile tolerance to bacterial endotoxin, lipopolysaccharide (LPS). Febrile tolerance to LPS was induced by daily intravenous (i.v.) injections of LPS (4 micrograms/kg, i.v.) for 5 days. In the LPS-tolerant rabbits, the second phase of the biphasic fever induced by i.v. injection of LPS (4 micrograms/kg) disappeared, although the first phase remained intact. In situ hybridization and immunohistochemical studies revealed that IL-1 beta production was observed in the circumventricular organs, such as the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area posterema (AP), 1 h after the first exposure to i.v. injection of LPS (4 micrograms/kg) (acute rabbits). In contrast, IL-1 beta production in these circumventricular organs disappeared in the LPS-tolerant rabbits. IL-1 beta production was observed in the spleens of the acute and the LPS-tolerant rabbits after i.v. injections of LPS. The cells which produced IL-1 beta in the spleen following LPS injections were confirmed to be monocytes/macrophages and polymorphonuclear leukocytes by immunohistochemistry in both the acute and the LPS-tolerant rabbits. The LPS injected acute rabbits showed a significant increase in the number of IL-1 beta immunoreactive monocytes/macrophages, compared with that in the saline-injected acute rabbits. However, there was no significant difference in immunoreactive cell numbers between the saline-injected acute and LPS-injected tolerant rabbits, or between the LPS-injected acute and the LPS-injected tolerant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796117 TI - Alzheimer paired helical filaments, untreated and pronase digested, studied by vertical platinum-carbon replication and high resolution transmission electron microscopy. AB - Untreated paired helical filaments (PHF) and pronase treated PHF filaments have been stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region, W = 22.8 +/- 2.4 nm, a narrow region width, T = 10.6 +/- 1.7 nm, and a helical turn period, L = 78.6 +/- 13.4. The widths of the pronase treated PHF were significantly reduced and had average measurements of W = 14.8 +/- 1.2 nm, T = 5.7 +/- 1.0 nm, with the helical period unchanged, L = 75.4 +/- 17 nm. The surfaces of the untreated PHF contained approximately 1.0 and approximately 0.4 nm strands, the size of normal and denatured tau monomer. The pronase treated PHF contained approximately 1.0 and approximately 0.4 nm strands as well as approximately 2.0 nm strands. The stereoscopic images of the untreated and the pronase digested PHF do not support a double helical morphology for the PHF. The PHF appear to be long helical ribbons. The approximately 1.0 and approximately 2 nm substructure has been organized both parallel and orthogonal to the PHF-core axis for distances less than 80 nm. The most frequent structural appearance is of a disorganized PHF core. The surfaces of the untreated PHF also have a similar disorganized appearance. PMID- 7796119 TI - Distinct neuroprotective profiles for sigma ligands against N-methyl-D-aspartate (NMDA), and hypoxia-mediated neurotoxicity in neuronal culture toxicity studies. AB - Substantiating evidence has raised the possibility that sigma ligands may have therapeutic potential as neuroprotective agents in brain ischemia. It has been suggested that the neuroprotective capacity of sigma ligands is related primarily to their affinity for the NMDA receptor complex and not to any selective action at the sigma binding site. However, sigma specific ligands, devoid of significant affinity for the NMDA receptor, are also neuroprotective via an inhibition of the ischemic-induced presynaptic release of excitotoxic amino acids. In the present study, we have investigated the potential neuroprotective effect of a comprehensive series of sigma ligands, with either significant (sigma/PCP) or negligible (sigma) affinity for the PCP site of the NMDA receptor, in order to delineate a selective sigma site-dependent neuroprotective effect. For this aim, we have employed two different neuronal culture toxicity paradigms implicating either postsynaptic-mediated neurotoxicity, (brief exposure of cultures to a low concentration of NMDA or Kainate) or pre- and postsynaptic mechanisms (exposure to hypoxic/hypoglycemic conditions). Only sigma ligands with affinity for the NMDA receptor [(+) and (-) cyclazocine, (+) pentazocine, (+) SKF-10047, ifenprodil and haloperidol] were capable of attenuating NMDA-induced toxicity whereas the sigma [(+)BMY-14802, DTG, JO1784, JO1783, and (+)3-PPP] and kappa opioid [CI-977, U-50488H] ligands, with very low affinity for the NMDA receptor, were inactive. The rank order of potency, based on the 50% protective concentration (PC50) value, of sigma/PCP ligands against NMDA-mediated neurotoxicity correlates with their affinity for the PCP site of the NMDA receptor, and not with their affinity for the sigma site. In addition sigma/PCP, sigma or kappa-opioid ligands failed to attenuate kainate-mediated neurotoxicity. On the other hand, sigma/PCP, sigma and kappa-opioid ligands were potent inhibitors of hypoxia/hypoglycemia-induced neurotoxicity, although their neuroprotective potency did not correlate with their affinity for either the sigma or PCP binding sites. In conclusion, the ability of sigma and kappa-opioid ligands to attenuate hypoxia/hypoglycemia, but not NMDA or kainate-induced toxicity, suggests that these drugs exert their neuroprotective role by a predominantly presynaptic mechanism possibly by inhibiting ischemic-mediated glutamate release. PMID- 7796120 TI - Cerebral protein synthesis alterations in response to acute and chronic immobilization stress in the rat. AB - The quantitative autoradiographic method with L-(35S)methionine was used to determine the effects of 1-acute (4h) and 2-chronic (14 days) immobilization stress followed by one week of recovery. Acute stress induced a significant decrease in methionine incorporation into proteins in 17 of the 35 brain structures examined (mean effect: -22%), and a significant increase in the prepositus hypoglossal nucleus (+23%). Chronic stress induced a significant decrease in methionine incorporation into proteins in 8 of the 35 structures analyzed. Only 4 structures were similarly affected in both these conditions. Our results indicate that stress-induced specific molecular changes in brain are also associated with changes in more general molecular components of cellular metabolism. PMID- 7796121 TI - Fos induced in brain of spontaneously hypertensive rats by angiotensin II and co localization with AT-1 receptors. AB - The induction of Fos-like immunoreactivity (FLI) by peripheral administration of angiotensin II (Ang II) was used to determine whether central activation was greater in spontaneously hypertensive rats (SHR) than in normotensive WKY and outbred Wistar controls. FLI was induced in the same brain regions (circumventricular organs and neurosecretory hypothalamic cell groups) in all three groups of rats, but the FLI in several of these regions was markedly less in WKY than in either SHR or Wistar. This reduced responsiveness in supraoptic and paraventricular nuclei was selective to Ang II, because the FLI induced in these nuclei by hypertonic NaCl did not differ between groups. We also report that a considerable number of cells in the SON and PVH expressing FLI to these stimuli show immunostaining with an antibody to the AT-1 Ang II receptor. These data indicate that central angiotensinergic pathways may be more sensitive in SHR than WKY, and that WKY are less sensitive than outbred Wistars. PMID- 7796122 TI - Neonatal monosodium glutamate treatment prevents effects of constant light on circadian temperature rhythms of adult rats. AB - Housing rats under continuous illumination (LL) disrupts circadian rhythms controlled by a pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The neural mechanisms underlying this effect are not well understood. The present study examined the effects of LL on circadian rhythms and on light induced expression of Fos protein in the SCN, intergeniculate leaflet (IGL), and ventrolateral geniculate nucleus (vLGN) in adult rats treated neonatally with monosodium glutamate (MSG). Such treatment is known to lead to acute degeneration of retinal ganglion cells. Despite degeneration of the optic nerve, neonatal MSG treatment (2 mg/g SC on postnatal days 1,3,5,7, and 9) had no effect on daily temperature rhythms in the adult animal under a light-dark cycle. However, the disintegration of circadian rhythms under LL conditions observed in adult rats treated neonatally with 10% saline was prevented in MSG-treated rats. Furthermore, neonatal MSG treatment attenuated light-induced expression of Fos protein in the IGL and vLGN, but not in the SCN. These data suggest that neonatal MSG treatment alters the response of the circadian system to LL and that cells within the IGL/vLGN region may mediate this response. PMID- 7796124 TI - Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. AB - Chronic antidepressant treatment results in adaptation of the NMDA receptor complex in the rodent cortex. This adaptation consists of a reduction in the potency of glycine to displace [3H]5,7-dichlorokynurenic acid from strychnine insensitive glycine receptors and a reduction in high affinity, glycine displaceable [3H]CGP-39653 binding to glutamate receptors. We hypothesized that dysfunction of NMDA receptors might occur in frontal cortices from human suicide victims. We now report that the proportion of high affinity, glycine displaceable [3H]CGP-39653 binding to glutamate receptors is reduced from 45 +/- 5% in controls to 27 +/- 6% in age- and post-mortem interval-matched suicide victims. In contrast, neither the potency nor the maximum efficacy of glycine to inhibit [3H]CGP-39653 binding is altered in the frontal cortex of suicide victims compared to controls. Moreover, neither the potency of glycine to inhibit [3H]5,7 dichlorokynurenic acid binding to the strychnine-insensitive glycine receptor nor the specific binding of [3H]5,7-dichlorokynurenic acid binding differed in suicide victims compared to controls. Likewise, neither basal nor glycine- or glutamate enhanced non-equilibrium binding of [3H]dizocilpine was altered in the frontal cortex of suicide victims compared to controls. These data represent the first demonstration supporting the hypothesis that glutamatergic dysfunction is involved in psychopathology underlying suicide and, potentially in human major depression. PMID- 7796123 TI - Lateralized effect of unilateral somatosensory cortex contusion on behavior and cortical reorganization. AB - Previous studies have shown that rats recover function after unilateral somatosensory cortex lesions, possibly by transfer of information processing to other brain areas not normally involved in those functions. In the present study, adult rats underwent unilateral contusions of the somatosensory cortex with ablation of the barrel receptor field. Behavioral testing with modified beam walking and sensory neglect tasks demonstrated persistent somatosensory deficits in rats with left contusions but no apparent deficits in right injured animals. After 2 months, the [14C]2-deoxyglucose (2-DG) method was used to show the metabolic activity produced by unilateral stimulation of the facial vibrissae. In left injured animals, cortical metabolic activity rostral and caudal to the injury site was depressed both under basal conditions and during right vibrissal stimulation. On the other hand, comparison of the pattern of [14C]2-DG uptake in the intact, right cortex revealed changes in the pattern of glucose utilization associated with left injury combined with right vibrissal stimulation. Pattern changes were quantified by measuring the area in which glucose utilization was within the highest 25% of this range (high activity area; HAA). Right vibrissal stimulation in left injured rats caused an expansion of this HAA in the intact occipital/temporal cortex. Also, in the intact somatosensory cortex of left injured rats, there was an enlarged HAA whether or not vibrissal stimulation was performed. Thus, a combination of depressed peri-injury metabolic activity and aberrant activity in remote brain areas occurs following unilateral somatosensory cortex injury. It remains to be shown whether these factors ameliorate or contribute to persistent behavioral deficits. PMID- 7796125 TI - Pelvic and pudendal reflexes in the in vitro neonatal rat preparation. AB - Pudendal-to-pelvic and pudendal-to-pudendal reflexes are described in an in vitro brainstem-spinal cord neonatal rat preparation. Cystometrograms and peripheral pelvic nerve recordings were used to monitor excitatory micturition reflexes evoked by tactile perineal stimulation or by continuous electrical stimulation of the sensory pudendal nerve. Micturition was characterized by an increased bladder pressure and a period of tonic pelvic nerve activity during which time fluid was expelled from the urethra. Single stimuli delivered to the sensory pudendal nerve evoked a phasic response in the pelvic nerve (pudendal-to-pelvic reflex) or pudendal motor nerve (pudendal-to-pudendal reflexes). The pudendal-to-pelvic reflex consisted of a single response occurring after a mean latency of 98 +/- 24 ms. The pudendal-to-pudendal reflex was comprised of two responses, the first occurred at a mean latency of 105 +/- 11 ms and the second at 383 +/- 36 ms. Cervical or lower thoracic spinal transection did not alter the pudendal-to pelvic reflex, however, the second component of the pudendal-to-pudendal reflex was abolished. The use of preganglionic pelvic and pudendal peripheral nerve recordings described in this study provide a direct measure of the reflex outflow from the CNS and can be used to examine developmental changes and neurochemical substrates within the CNS which contribute to micturition and coital reflexes in the rat. PMID- 7796126 TI - Noradrenergic enhancement of GABA-induced input resistance changes in layer V regular spiking pyramidal neurons of rat somatosensory cortex. AB - Previous in vivo studies have shown that microiontophoretic application of norepinephrine (NE) and isoproterenol (ISO) can enhance gamma-aminobutyric acid (GABA)-induced depressant responses of rat somatosensory cortical neurons. In the present investigation we have examined the transmembrane electrophysiological events which are associated with interactions between NE and GABA in layer V pyramidal neurons of rat barrel field cortex. Intracellular recordings were made from electrophysiologically identified cells in a superfused cortical tissue slice preparation before, during and after bath or microdrop application of GABA, NE and ISO, alone or in combination. GABA application produced a small depolarization from resting membrane potential associated with a reduction (22%) in input resistance. NE and ISO (10-100 microM) also produced in some cases small membrane depolarizations (1-4 mV) but little concomitant changes in input resistance. Simultaneous application of NE with GABA potentiated amino acid induced changes in input resistance in 4 cases and antagonized (n = 4) or had no effect (n = 4) on GABA-associated membrane events in 8 other cases. When the alpha-blocker, phentolamine (20 microM), was added to the medium, NE-induced enhancement of the GABA response was observed in 3 of 5 cases (60%), suggesting both, a beta-adrenergic mediation and a possible alpha-receptor masking of this noradrenergic-potentiating action. Consistent with this interpretation was the finding that the beta-agonist, ISO (10-100 microM), produced net increases in GABA-induced input resistance changes in 64% of cases tested (9 of 14). The potentiating effect of NE and ISO was mimicked by the adenyl cyclase activator, forskolin (n = 2), and a membrane permeant analog of cyclic-AMP, 8-bromo-cyclic AMP (n = 3); and could also be demonstrated when the GABAA agonist muscimol (0.5 1 microM) was substituted for GABA. The reversal potential for GABA and GABA + NE remained the same. These findings suggest that previous demonstrations of NE potentiating effects on GABA inhibition may be mediated by beta-receptor/cyclic AMP-linked actions on mechanisms which regulate GABAA receptor-induced membrane conductance changes. PMID- 7796127 TI - Detection of D-aspartate in tau proteins associated with Alzheimer paired helical filaments. AB - Paired helical filaments (PHF) characteristic of Alzheimer neurofibrillary lesions are known to contain a modified form of microtubule associated protein tau. These proteins, PHF-tau, differ from normal tau in the extent and the site of phosphorylation. To determine whether PHF-tau, tau proteins from normal adult brains (N-tau), tau proteins from Alzheimer brains not associated with PHF (A tau), and tau proteins from fetal brains (F-tau) differ in racemization, these proteins were compared for their D-aspartate content. The results demonstrated that PHF-tau contain more D-aspartate than N-tau, A-tau and F-tau. The average percentage D-aspartate for these proteins, after a correction for background, are 4.9%, 2.8%, 1.6%, and 1% for PHF-tau, N-tau, A-tau and F-tau, respectively. It remains to be determined if the increase in D-aspartate is a consequence of PHF formation. It is also unknown if the change in D-aspartate content in PHF-tau is associated with phosphorylation, which alters the susceptibility of tau to proteolysis. PMID- 7796128 TI - Involvement of nitric oxide in intracerebroventricular beta-endorphin-induced neuronal release of methionine-enkephalin. AB - Previous work has suggested that the antinociceptive effect of nitrous oxide (N2O) in rats is mediated, at least in part, by beta-endorphin (beta-EP) and that centrally administered beta-EP stimulates release of methionine-enkephalin (ME) in the rat spinal cord. Since inhibition of central nitric oxide (NO) production has been found to suppress N2O antinociception, we examined the possible involvement of NO in the release of spinal cord ME by i.c.v. beta-EP. Urethane anesthetized, male Sprague-Dawley rats were intrathecally (i.t.) perfused with artificial cerebrospinal fluid (aCSF) and fractions of perfusate were assayed for immunoreactive (i.r.) ME. The beta-EP-induced increase in ME concentration in the i.t. perfusate was significantly suppressed by perfusing the animal with aCSF containing 100 microM L-NG-nitro arginine (L-NOARG), an inhibitor of NO synthase (NOS). The further addition of 50 microM L-arginine (L-ARG), but not D-arginine (D-ARG), to the aCSF reversed the suppression of the ME change by L-NOARG. However, the potency of L-ARG decreased with increasing concentrations of L-ARG. On the other hand, increasing the concentration of L-NOARG in the aCSF to 250 microM failed to produce a greater suppression of the beta-EP-induced increase in ME. These findings suggest that NO may mediate the beta-EP-induced release of ME in the spinal cord and that interference with this mechanism might be an explanation for the antagonism of N2O antinociception in rats by NOS inhibitors. PMID- 7796130 TI - The role of strain/vendor differences on the outcome of focal ischemia induced by intraluminal middle cerebral artery occlusion in the rat. AB - This study investigated the role of strain and vendor differences on the outcome of focal cerebral ischemia in the rat induced by occlusion of the middle cerebral artery by an intraluminal thread. The cortical infarct volumes (Mean +/- S.E.M.) were: 14.2 +/- 6.2 mm3 in Simonsen Laboratories Sprague-Dawley rats; 84.0 +/- 22.9 mm3 in Simonsen Laboratories Wistar rats; 223.3 +/- 23.6 mm3 in Taconic Laboratories Sprague-Dawley rats; and 239.5 +/- 30.7 mm3 in Charles River Laboratories Sprague-Dawley rats. Middle cerebral artery occlusion combined with bilateral common carotid artery occlusion for 60 min increased cortical infarct volumes to: 113.0 +/- 18.8 mm3; 152.4 +/- 21.1 mm3; 227.8 +/- 19.3 mm3; and 248.4 +/- 24.0 mm3, respectively. To control the effect of blood pressure as a variable contributing to the outcome of ischemia, additional experiments where performed in which the blood pressure in Simonsen Laboratories Sprague-Dawley rats was lowered to the level of the blood pressure in Taconic Laboratories Sprague-Dawley rats. Although this manipulation increased the cortical infarct volumes in Simonsen Laboratories Sprague-Dawley rats, the volumes were still less than those in Taconic Laboratories Sprague-Dawley rats. The results of the present study indicate that the outcome of ischemia in the intraluminal thread model may dramatically differ depending on the strain and vendor of animal used. PMID- 7796129 TI - Effects of the histaminergic system on the morphine-induced conditioned place preference in mice. AB - The effects of an H2 receptor antagonist, a histidine decarboxylase inhibitor and a histamine precursor on the morphine-induced place preference in mice were examined. Morphine (1-7 mg/kg) produced a place preference in a dose-dependent manner. This morphine-induced place preference was significantly antagonized by the dopamine (DA) D1 receptor antagonist SCH 23390. The histamine precursor, L histidine, attenuated the morphine (7 mg/kg)-induced place preference. On the other hand, the histidine decarboxylase inhibitor, alpha-fluoromethylhistidine (alpha-FMH), significantly potentiated the morphine (1 mg/kg)-induced place preference. This potentiation was antagonized by SCH 23390. The H2 receptor antagonist zolantidine (0.3 mg/kg) significantly potentiated the morphine-induced place preference. Surprisingly, zolantidine (1 mg/kg) alone also produced a significant place preference. The zolantidine-induced place preference was antagonized by SCH 23390. In addition, zolantidine (1, 3 and 10 mg/kg) significantly increased DA turnover (DA ratio) in the limbic forebrain (nucleus accumbens and olfactory tubercle), implying that zolantidine may activate the mesolimbic DA system. Moreover, co-administration of zolantidine dose-dependently increased morphine (10 mg/kg)-induced DA turnover in the limbic forebrain. These results suggest that the activation of histaminergic neurons may attenuate the rewarding effect of morphine, while the inhibition of histaminergic neurons may potentiate the rewarding effect of morphine. Furthermore, potentiation of the morphine-induced rewarding effect by inhibition of histaminergic neurons may be mediated by D1 receptors. We also demonstrated that the H2 receptor antagonist zolantidine may activate the mesolimbic DA system, and as a result, zolantidine itself produces a rewarding effect and potentiates the morphine-induced rewarding effect. PMID- 7796131 TI - Electrophysiological evidence for glutamate as a vomeronasal receptor cell neurotransmitter. AB - Bipolar receptor cells in the vomeronasal organ send axonal projections to the accessory olfactory bulb where they synapse with mitral cell dendrites. Although the nature of the synapse is thought to be excitatory, the neurotransmitter(s) involved has not yet been identified. Electrophysiological recordings of single neurons in the mitral cell layer of the AOB in response to vomeronasal nerve stimulation were conducted to characterize the synaptic response and the underlying neurotransmitter substance. Extracellular activity was recorded in vivo (whole animal) and in vitro (AOB slice) from female rats. In vivo, the predominant response to stimulation of the VNO was excitation. In many instances in the whole animal preparation, the excitation was followed by an inhibitory response. Attempts to block the excitatory response by ejecting kynurenic acid in close proximity to the mitral cell being recorded were not successful. Since this failure may have been due to inability of the antagonist to reach its presumed site of action at the dendrite, further recordings were carried out in vitro. In the AOB slice preparation, the predominant response to stimulation of the VN nerve endings was excitation. Superfusion of the non-NMDA antagonist, CNQX, into the medium resulted in a reduction of the orthodromic excitation in 5 of 8 cells. The NMDA antagonist, AP-5, was found to blunt orthodromic excitation in 1 of 4 cells. These results suggest that the excitatory response evoked in mitral cells followng stimulation of the VN nerve is mediated by glutamate. PMID- 7796132 TI - Short and long-term changes in dopamine and serotonin receptor binding sites in amphetamine-sensitized rats: a quantitative autoradiographic study. AB - The biochemical changes in DA and 5HT systems were investigated in amphetamine (AMPH)-sensitized rats, 1 and 15 days after cessation of treatment (5 mg/kg AMPH, i.p., twice a day for 6 days). At both times, AMPH-treated rats exhibited behavioral sensitization, as revealed by an enhancement of the stereotypic response to a challenge dose of 2 mg/Kg, ip. AMPH. Basal dopamine (DA) and serotonin (5-HT) metabolism was not significantly modified in different brain areas of AMPH-sensitized rats. Quantitative autoradiographic analysis of DA and serotonin 5-HT receptor subtypes was performed in the following brain regions: medial prefrontal cortex, nucleus accumbens, striatum, substantia nigra, ventral tegmental area, dorsal and median raphe nuclei. A significant increase of [3H]SCH 23390 binding to D1 DA receptors was observed in the substantia nigra pars reticulata 1 day but not 15 days after the cessation of AMPH treatment, whereas [3H]8-OH-DPAT binding to 5-HT1A sites was found to be significantly enhanced in the dorsal raphe nucleus at both time points. No change in D2 DA nor in 5-HT1B or 5-HT2A receptors was found in any of the brain structures examined at either time point. The obtained results suggest that DA and 5-HT systems are differently and time-dependently involved in AMPH-induced behavioral sensitization. PMID- 7796134 TI - Angiotensin II receptor subtypes in the human central nervous system. AB - The distribution of the AT1 and AT2 subtypes of angiotensin II receptor was mapped in the adult human central nervous system using quantitative in vitro autoradiography. Binding in all forebrain, midbrain, pontine, medullary and spinal cord sites where angiotensin II receptors have previously been described is of the AT1 subtype, as is binding in the small and large arteries in the adjacent meninges and in choroid plexus. By contrast, both AT1 and AT2 receptors occur in the molecular layer of the cerebellum. Angiotensin II AT1 receptors in the brain show a moderate degree of conservation across mammalian species studied so far, whereas expression of AT2 receptors is more variable, and is more restricted in the human CNS than in many other mammals. These differences between the subtype distributions in humans and other animals indicate the need for care when extrapolating the results of animal studies involving the brain angiotensin system. PMID- 7796133 TI - Chronic hypoxia causes opposite effects on glucose transporter 1 mRNA in mature versus immature rat brain. AB - We have shown previously that chronic hypoxia can regulate the expression of membrane proteins. Since there are virtually no glucose stores in the brain and glucose transport can be rate-limiting during stress, the role of glucose transporters becomes crucial for cell survival under stress. In the present study, we asked whether mRNA levels for glucose transporter 1 (GT1), which is expressed in a variety of cells in the brain, especially in the microvessels for glucose transport from blood vessels to brain, change in response to chronic hypoxia. Because major developmental changes occur in the rat CNS in-utero and in the first few weeks postnatally, we studied brain GT1 mRNA using Northern blot analysis at different ages after exposure of fetuses (from embryonic day 10 to birth), developing rats (from birth to 30 day old) or adult rats (from 90 to 120 day old) to hypoxia (Fractional inspired O2 9%). Our data show that (i) GT1 mRNA level was much lower in the newborn than in the adult and increased with age; (ii) chronic hypoxia caused a decrease of approximately 65% in GT1 mRNA in adult brain but induced an increase in fetal (more than 50%) and developing (approximately 80%) rats and (iii) the response of housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase) was not similar to that of GT1, suggesting that the changes of GT1 mRNA are specific to glucose transporter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796135 TI - Experimental analysis of the method of 'peeling' exponentials for measuring passive electrical properties of mammalian motoneurons. AB - Trigeminal motoneurons of the guinea pig brain stem slice preparation were studied using intracellular recording techniques. The voltage response to a 100 ms constant-current pulse was studied and a population of cells was found which did not exhibit sag or overshoot of their voltage response to a pulse of hyperpolarizing current of < 1 nA but did exhibit both phenomena when a current pulse of > 1 nA was used. The sag and overshoot observed with large-current pulses were reduced or blocked when 4 mM CsCl was added to the bathing solution. This observation supports the hypothesis that these phenomena were due to the voltage- and time-dependent activation of the Q-current. The method of peeling exponentials was then used to correct raw voltage data from cells in which the Q current was present. The mean membrane time constant was within 1% and the mean input resistance was within 2% of the means for these parameters when measured in these same cells under conditions in which the Q-current was absent. We conclude from these experiments that the method of peeling exponentials is valid for obtaining estimates of the membrane time constant and input resistance from cells that exhibit sag and overshoot due to voltage- and time-dependent changes in the magnitude of the Q-current. PMID- 7796137 TI - The role of nitric oxide in opioid-induced pial artery vasodilation. AB - The present study was designed to investigate the role of nitric oxide (NO) and the production of cGMP in the vasodilator response to opioid agonists in newborn pigs equipped with a closed cranial window. Methionine-enkephalin (10(-8), 10(-6) M), an endogenous mu opioid agonist, produced pial artery dilation that was attenuated by L-nitroarginine (LNA, 10(-6) M), an NO synthase inhibitor (10 +/- 1 vs. 4 +/- 1 and 16 +/- 1 vs. 7 +/- 1% for 10(-8), 10(-6) M methionine-enkephalin, respectively). Methionine-enkephalin-induced vasodilation was associated with increased cortical periarachnoid CSF cGMP and these changes in CSF cGMP were attenuated by LNA (354 +/- 11 and 596 +/- 32 vs. 278 +/- 13 and 266 +/- 19 fmol/ml for control and methionine-enkephalin 10(-6) M before and after LNA, respectively). Leucine enkephalin, an endogenous delta agonist, elicited similar changes in pial diameter and CSF cGMP while dynorphin, an endogenous k agonist, produced dilation associated with large increases in CSF cGMP (374 +/- 18 vs. 1054 +/- 45 fmol/ml for control and dynorphin 10(-6) M, respectively). Vascular and biochemical changes for these two opioids were similarly attenuated by LNA. The synthetic selective opioid receptor agonists, DAMGO, DPDPE, deltorphin, and U50,488H (10(-8), 10(-6) M) mu, delta 1, delta 2, and kappa agonists, respectively, also elicited increases in pial artery diameter and CSF cGMP that were similarly attenuated by LNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796138 TI - Quantitative autoradiographic localization in rat brain of alpha 2-adrenergic and non-adrenergic I-receptor binding sites labelled by [3H]rilmenidine. AB - alpha 2A-Adrenergic receptor (AR) and non-adrenergic imidazoline receptor (I-R) binding sites have been previously characterized in rat cerebral cortex membranes using the N-substituted oxazoline, [3H]rilmenidine ([3H]Ril) [King, P.R. et al., Eur. J. Pharmacol., 218 (1992) 101-108]. In the present study, in vitro autoradiography was used to quantify the regional distribution of these receptors throughout the rat neuroaxis. The distribution and relative density (fmol/mg tissue) of I-Rs was examined in the presence of 1 microM adrenaline to block the adrenergic component of 40 nM [3H]Ril binding and non-specific binding was measured in the presence of another oxazoline, Bay a6781 (10 microM). Both alpha 2A-ARs and I-Rs were broadly, but heterogeneously, distributed. In forebrain, high levels of [3H]Ril-labelled alpha 2A-AR sites were observed in the anterior olfactory nucleus, the piriform, entorhinal and perirhinal cortices, lateral septum, bed nucleus of the stria terminalis, several thalamic nuclei, the amygdala and the arcuate, dorsomedial and posterior hypothalamic nuclei. In hindbrain, alpha 2A-AR sites were concentrated in locus coeruleus, lateral parabrachial nucleus, nucleus of the solitary tract and area postrema. I-R sites accounted for 50% or more of specific [3H]Ril binding (40 nM) in most cortical and hypothalamic nuclei, nucleus of the solitary tract, cranial motor nuclei and most spinal cord layers. The highest densities of I-Rs were found in the arcuate, dorsomedial and posterior hypothalamic nuclei, the locus coeruleus, the area postrema, the cranial motor nuclei and associated with spinal motor neurones. A very high concentration of I-Rs was also detected in the pineal gland. The distribution of alpha 2-AR sites determined resembled that reported with [3H]p aminoclonidine which appears to specifically label alpha 2-ARs and not I1-R sites in rat brain sections, and [3H]methoxyidazoxan which is a selective alpha 2-AR antagonist. The regional and cellular distribution of I-R binding sites was unlike the distribution of putative I1-R sites labelled by [3H]clonidine in human brain, although comparable autoradiographic mapping studies in rat brain have not been done using this ligand. The regional and cellular distribution of [3H] labelled I-R binding sites had both similarities and differences to that reported using the imidazoline ligand, [3H]idazoxan, with common labelling of areas such as area postrema, arcuate and interpeduncular nuclei and pineal gland with the two ligands, and differential relative binding levels ([3H]Ril > [3H]idazoxan) associated with hippocampal pyramidal cells and brainstem and spinal motor neurones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7796136 TI - Ca(2+)- and Cl(-)-dependent, NMDA receptor-mediated neuronal death induced by depolarization in rat hippocampal organotypic cultures. AB - The neurotoxicity induced by depolarization with high-K+ was investigated in rat hippocampal organotypic slice cultures. The exposure of cultures to 90 mM K+ solution for 30 min caused a severe neuronal injury in CA1 region while less damage was observed in CA3 and dentate gyrus over the following day. This neurotoxicity was prevented in a concentration dependent manner by NMDA antagonist MK-801 or CPP. Non-NMDA antagonist, DNQX, had no protective effect. Omission of Ca2+ from the exposure solution prevented the neurotoxicity. Voltage dependent Ca2+ channel blockers, nifedipine and flunarizine, failed to prevent the neurotoxicity. These results suggest that the Ca2+ influx through the NMDA receptor is predominantly involved in this neurotoxicity. Apparent tissue swelling was observed immediately after the depolarization. This swelling was completely inhibited by omission of Cl- from the exposure solution, accompanied with complete protection against neurotoxicity. This suggests that Cl(-) dependent tissue swelling also largely contributes to the neurotoxicity. Depolarization with application of MK-801 (10 microM) or omission of Ca2+ from the solution still caused apparent swelling, despite these treatment protected neuronal death. We hypothesize that Cl(-)-dependent tissue swelling may be involved in the release of the excitatory amino acid, which activates the NMDA receptor. PMID- 7796139 TI - Inhibition of growth factor-induced DNA synthesis in astrocytes by ligands of peripheral-type benzodiazepine receptors. AB - The effect of diazepam and specific ligands of peripheral-type benzodiazepine receptors (PBRs) on growth factor-induced DNA synthesis in quiescent cultures of rat astrocytes has been examined. It was found that diazepam inhibited the ability of basic fibroblast growth factor (bFGF) to stimulate [3H]thymidine incorporation; the IC50 was approximately 5 microM. Ro5-4864, a specific agonist of PBRs, also blocked bFGF-induced DNA synthesis. PK11195, which in some cases functions as an antagonist of PBRs, did not prevent the effect of Ro5-4864 on bFGF-induced DNA synthesis; rather, addition of PK11195 also inhibited bFGF induced DNA synthesis. In addition, diazepam reduced the stimulation of DNA synthesis caused by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), polypeptide growth factors coupled to receptor tyrosine kinases, as well as thrombin, an activator of G protein-coupled receptors. These data suggest that ligands of PBRs may limit astrocyte mitosis, a phenomenon that occurs following CNS injury. PMID- 7796140 TI - Methyl-beta-carbolinium analogs of MPP+ cause nigrostriatal toxicity after substantia nigra injections in rats. AB - Eleven beta-carbolinium compounds (beta C+s) and MPP+ were stereotaxically injected (40-200 nmol in 5 microliter of vehicle) unilaterally into the substantia nigra of anesthetized adult male Sprague-Dawley rats. The rats were sacrificed after three weeks. The ipsilateral striatum was analyzed for dopamine and DOPAC levels with HPLC. The brainstem injection site was fixed and cut coronally. The largest lesion area in each animal was measured using NIH IMAGE. Three beta C+s produced lesions whose mean areas were nearly as large as that produced by MPP+ (defined as 100%): 2,9-Me2-harman (94%), 2-Me-harmol (74%), and 2,9-Me2-norharman (57%). Three other compounds produced somewhat smaller lesions: 2-Me-harmaline (34%), 6-MeO-2-Me-harman (29%), and 2-Me-harmine (25%). The remaining compounds were ineffective (< or = 12%): norharman, 2-Me-norharman, 2 Me-harman, harmine, and 2-Me-6-MeO-harmalan. A 40 nmol dose of MPP+ reduced ipsilateral striatal dopamine to 0.6% of control. None of the beta C+s approached this, although several did significantly reduce striatal dopamine at doses of either 40 nmol (2,9-Me2-harman (37%), 2,9-Me2-norharman (42%), and 2-Me-harman (63%)) or 200 nmol (2-Me-harmaline (23%), norharman (63%), and 2-Me-norharman (64%)). There was a moderate negative correlation between lesion size and dopamine level (r = -0.65). There were also moderately strong correlation between lesion size and dopamine level (r = -0.65). There were also moderately strong correlations (r = 0.39-0.78) between the beta C+ nigral lesion area or striatal dopamine level potencies and their previously described IC50 values for inhibiting mitochondrial respiration or their toxicity to PC12 cells in culture. Interestingly, our correlation analysis revealed a remarkably strong correlation between beta C+ Ki MAO-A values and their toxicity to PC12 LDH release (r = 0.84) or PC12 protein loss (r = 0.79). Although beta C+s appear to be less specific toxins than MPP+, their levels in human substantia nigra are 8-20-fold higher than in cortex, making their role as relatively selective nigral toxins in Parkinson's disease plausible. PMID- 7796141 TI - Contribution of L- and N-type calcium currents to exocytosis in rat adrenal medullary chromaffin cells. AB - The excitation-secretion coupling process requires Ca2+ influx through voltage dependent Ca2+ channels (VDCC) but the contribution of L-type or N-type VDCC during the secretion from adrenal chromaffin cell is still on debate. In this study we explored the contribution of each VDCC to exocytosis in single rat adrenal chromaffin cells. Chromaffin cells were voltage-clamped clamped in the whole-cell recording mode. Ca2+ inward current (ICa) was elicited by depolarization from -70 mV to +10 mV and the change in cell membrane capacitance (Cm) was monitored as an indicator of the resultant exocytosis. The increase in Cm had positive correlation with the amount of ICa and replacing the internal Ca2+ buffer to high EGTA (5 mM) decreased the sensitivity of Cm increase to Ca2+ influx. After blockage of ICa with 100 microM Cd2+, there was no increase in Cm following membrane potential depolarization while INa was intact. To clarify the contribution of each type of VDCC to induce exocytosis during membrane potential depolarization, L- and N-type ICa were blocked selectively by Ca2+ channel antagonists. After blockage of L-type ICa with nicardipine (1 microM), ICa was blocked to 35 +/- 6.2% (mean +/- standard error) of control and the resultant change in Cm was reduced to 38 +/- 4.6% of control. Bay K-8644 (1 microM) enhanced ICa and the similar proportion of Cm was increased by this L-type VDCC agonist. On the other hand omega-conotoxin GVIA (1 microM), an N-type VDCC antagonist, blocked ICa to 60 +/- 4.3% of control and reduced the change in Cm to 58 +/- 3.9% of control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796142 TI - Prenatal stress increases corticotropin-releasing factor (CRF) content and release in rat amygdala minces. AB - Corticotropin-releasing factor (CRF) is a neuropeptide found throughout the central nervous system that has a proposed role in modulating emotional and behavioral states, including stress and anxiety. The amygdala, which is important in the control of emotional and autonomic responses to stress, contains CRF nerve terminals, CRF cell bodies, and CRF receptors. In rats, exposure to prenatal stress results in offspring that display a hyperemotional state and increased anxiety. In this study the effects of prenatal stress on CRF release was measured in amygdala minces (1 mm3) obtained from adult (8-16 weeks of age) male offspring of dams subjected to daily saline injection (0.1 ml, s.c.) from gestational day 14 to 21. CRF release from amygdala was time- and calcium-dependent, and stimulated by KCl-induced depolarization. Depolarization-induced CRF release was significantly increased by 42% from the amygdala of prenatally stressed offspring versus controls. Prenatally stressed offspring also showed a 49% increase in CRF levels in the amygdala. The increased amounts of CRF released in response to depolarization were likely the consequence of increased tissue content of CRF, as fractional release under basal or KCl-stimulated conditions was not different in the prenatal stress group versus control. This suggests that a long-lasting up regulation of the CRFergic neurotransmission may occur in the amygdala, which may be important in the generation of hyperemotional offspring after exposure to prenatal stress. PMID- 7796143 TI - Distribution of calbindin-D28K in the brain of the fetal sheep in late gestation. AB - Immunocytochemical distribution of calbindin-D28K was examined in the brains of fetal sheep at 100-105 and 120-125 days of gestation (dGA) and at term in labor (term approximately 150 dGA) and compared to adult sheep. Brains were perfused, cut frozen and immunostained as freely floating sections with a polyclonal anti calbindin-D28K antibody. Light microscopy revealed that calbindin-D28K immunogenicity in fetal cerebellum, rhombencephalon, mesencephalon, diencephalon and telencephalon was overall very similar to that seen in the brains of adult sheep. In addition even though fetal sheep peripheral plasma cortisol concentrations increase 10-20 times over the last 3-4 weeks of gestation to peak during labor and delivery, no glucocorticoid dependent increases in calbindin D28K in the hippocampal formation could be seen in the sheep fetus as have been demonstrated for the adult rat given exogenous glucocorticoids. It is concluded that: (1) the basic pattern of calbindin-D28K distribution seen in adult sheep brains is established by at least 100 dGA in the sheep fetus; and (2) the pattern of calbindin-D28K expression in fetal sheep hippocampal formation is not related to peripheral plasma glucocorticoid concentrations. PMID- 7796144 TI - Inhibition of morphine tolerance and dependence by diazepam and its relation to cyclic AMP levels in discrete rat brain regions and spinal cord. AB - Diazepam inhibits morphine tolerance and dependence and reverses a decrease in the met-enkephalin level in brain induced by morphine. In this study, we investigated whether inhibition of morphine-induced tolerance and dependence by diazepam involved a change in cyclic AMP levels in discrete rat brain regions and spinal cord. Male Sprague-Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b. wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Tail flick antinociception was measured 1 h after injections everyday. Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5), and the jumping behavior was observed for 30 min. Concomitant treatment with diazepam (0.25 mg/kg) significantly decreased the development of morphine tolerance and dependence. Diazepam (0.25 mg/kg) treated rats also showed a significant decrease in the jumping behavior compared to animals treated with morphine alone. Rats were sacrificed 2 h after the injection of saline or diazepam (0.25 mg/kg) on the fifth day. Cyclic AMP was estimated by RIA. In the control rats, the concentration of cyclic AMP in cortex was > hippocampus > cerebellum > hypothalamus > striatum > midbrain > pituitary > pons/medulla > spinal cord. There was no change in the concentration of cyclic AMP in any of the brain regions examined from morphine tolerant animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796145 TI - Immunocytochemical evidence for vesicular storage of glutamate in cat spinocervical and cervicothalamic tract terminals. AB - The densities of synaptic vesicles and gold particles, signaling fixed glutamate, were examined in spinocervical and cervicothalamic tract terminals. Statistically significant positive correlations between these parameters were detected in both terminal populations, whereas presumed inhibitory profiles displayed insignificant or negative correlations. These findings indicate a vesicular storage of glutamate in spinocervical and cervicothalamic tract terminals, and thus provide further evidence for glutamate as a neurotransmitter in the spinocervicothalamic pathway. PMID- 7796146 TI - Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress. AB - A microdialysis probe was placed in either the shell or core compartment of the nucleus accumbens and rats were exposed to mild footshock. Extracellular dopamine levels in the shell of the nucleus accumbens were elevated during the 20-min collection period immediately after discontinuing footshock. In contrast, the levels of dopamine remained unaltered in the core of the nucleus accumbens. PMID- 7796147 TI - Herpes simplex virus induces Fos expression in rat brainstem neurons. AB - After the injection of Herpes Simplex Virus type 1 into the rat cervical vagus nerve, transneuronally labelled virus-containing neurons and glial cells were present in the medulla oblongata. Fos-containing nuclei were present in the same regions of the brain. A double-labelling procedure revealed that most of the virus-positive neurons also contained Fos-positive nuclei. Appearance of HSV1 antigen within the CNS is associated with Fos expression in neurons and glial cells. PMID- 7796149 TI - Parvalbumin and calbindin D-28k in vagal and glossopharyngeal sensory neurons of the rat. AB - Parvalbumin- and calbindin D-28k-immunoreactivities (ir) were examined in the glossopharyngeal and vagal sensory ganglia (petrosal, nodose and jugular ganglia), the carotid sinus nerve and the carotid body. Parvalbumin-ir nerve cells were mostly localized in the petrosal and nodose ganglia and were rare in the jugular ganglion. Calbindin D-28k-ir nerve cells were found in moderate and large numbers in the petrosal and nodose ganglia, respectively. Only a few calbindin D-28k-ir nerve cells were observed in the jugular ganglion. The carotid sinus nerve and carotid body contained numerous calbindin D-28k-ir nerve fibers but few parvalbumin-ir nerve fibers. Studies of the coexistence of these calcium binding proteins with calcitonin gene-related peptide (CGRP)- and tyrosine hydroxylase (TH)-ir showed that CGRP-ir was rarely colocalized in parvalbumin- or calbindin D-28k-ir nerve cells in the petrosal or nodose ganglion. Moreover, TH ir was not generally contained in parvalbumin-ir nerve cells in the petrosal, nodose and jugular ganglia while a portion (15-19%) of calbindin D-28k-ir neurons in the petrosal and nodose ganglia colocalized TH-ir. These findings are consistent with the involvement of calcium-binding proteins, particularly calbindin D-28k, in the function of visceral sensory neural systems of the glossopharyngeal and vagus nerves and, perhaps, in baro- and chemoreceptor neurotransmission. PMID- 7796148 TI - Bicuculline blocks neuropeptide Y-induced phase advances when microinjected in the suprachiasmatic nucleus of Syrian hamsters. AB - Microinjection of neuropeptide Y (NPY) into the suprachiasmatic nucleus of the hypothalamus (SCN) during the middle of the subjective day (i.e. circadian time 6) causes large phase advances in circadian rhythms. The present study demonstrates that microinjection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline, completely blocks NPY-induced phase advances. These data indicate that GABAA activity within the SCN may mediate the phase shifting effects of some stimuli on the circadian pacemaker. PMID- 7796150 TI - Radioligand-binding study of noribogaine, a likely metabolite of ibogaine. AB - Radioligand-binding studies were performed to ascertain the actions of noribogaine, a suspected metabolite of ibogaine, on opioid receptors. Consistent with previous results, ibogaine showed highest affinity for kappa opioid receptors (Ki = 3.77 +/- 0.81 microM), less affinity for mu receptors (Ki = 11.04 +/- 0.66 microM) and no affinity for delta receptors (Ki > 100 microM). Noribogaine showed a higher affinity than ibogaine for all of the opioid receptors: kappa Ki = 0.96 +/- 0.08 microM, mu Ki = 2.66 +/- 0.62 microM and delta Ki = 24.72 +/- 2.26 microM. These data suggest that noribogaine is active in vivo and that it may contribute to ibogaine's pharmacological effects. PMID- 7796151 TI - Effect of constant temperatures, darkness and light on the secretion of melatonin by pineal explants and retinas in the gecko Christinus marmoratus. AB - The effects of temperature and lighting conditions on the secretion of melatonin by the pineal organ of the nocturnal gecko Christinus marmoratus was studied using in vitro perifusion. In a 12L:12D lighting regime, a high-amplitude melatonin rhythm was detectable at a constant temperature of 20 and 30 degrees C but not at 10 or 37 degrees C. There were sustained high levels of melatonin in constant darkness and sustained low levels in constant light. No retinal melatonin was detected using static and perifusion culture techniques. These results show that the pineal organ of C. marmoratus maintains light sensitivity in vitro but does not contain an oscillator coupled to the melatonin synthetic pathway. PMID- 7796152 TI - Glycine site NMDA receptor antagonists provide protection against ischemia induced neuronal damage in hippocampal slice cultures. AB - Ischemia-induced neuronal injury can be reduced by glutamate antagonists acting at the N-methyl-D-aspartate (NMDA) receptor. 7-Chlorokynurenic acid and the recently synthesized compound Acea 1021 block NMDA receptors by acting at the strychnine-insensitive glycine site. The anti-ischemic properties of these compounds were tested by evaluating their ability to reduce CA1 neuronal damage in hippocampal slice cultures deprived of oxygen and glucose. Acea 1021 and 7 chlorokynurenic acid significantly reduced CA1 injury produced by oxygen and glucose deprivation in a dose-dependent manner. The neuroprotective effect of these compounds was reversed by the addition of glycine. The phencyclidine site NMDA antagonist MK-801 also provided significant protection to CA1 neurons against the same insult, and this protection was not affected by the addition of glycine. These results indicate that Acea 1021 and 7-chlorokynurenic acid can provide protection to CA1 neurons against ischemia-induced injury by a glycine sensitive mechanism. PMID- 7796153 TI - Brain chimeras for the study of an avian model of genetic epilepsy: structures involved in sound and light-induced seizures. AB - The epileptic homozygotes of the Fayoumi strain of chickens (Fepi) are affected by photogenic reflex epilepsy with complete penetrance. Here we demonstrate that they are equally affected by audiogenic reflex epilepsy induced by intense sound stimulation. All the Fepi display sound-induced seizures from hatching to adulthood consisting of initial 'ictal arousal' and running fits usually followed by generalized clonico-tonic convulsions. A running fit is the preconvulsive motor symptom specifically induced by auditory stimulation while neck myoclonus is the preconvulsive motor symptom specifically induced by photic stimulation. The EEG interictal spikes and spike and waves are suppressed and replaced by a desynchronized trace during the seizures of both kinds. Viable neural chimeras were obtained by graft of embryonic brain vesicles from Fepi donors into normal chick embryos. Transfer of the complete audiogenic and photogenic phenotypes was obtained in chimeras resulting from embryonic substitution of both the prosencephalon and mesencephalon. The substitution of the prosencephalon alone resulted in transfer of interictal paroxysmal EEG activity accompanied by the sound and light-induced desynchronization and 'ictal arousal' with no motor seizures. Chimeras with embryonic substitution of the mesencephalon alone displayed running fits and convulsions induced by sound stimulation but only neck myoclonus following light stimulation. The conclusions are reached that: (i) the Fepi is a model of audiogenic and photogenic reflex epilepsy; (ii) in both types, the seizure initiator and the convulsion generator are localized in the brainstem, although reinforcement from telencephalic visual structures is needed to trigger photogenic generalized convulsions. PMID- 7796154 TI - Caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night. AB - Adenosine has been implicated in the physiological regulation of sleep propensity. The adenosine-receptor-antagonist, caffeine (100 mg), administered immediately prior to a nocturnal sleep episode, has previously been shown to lower sleep propensity as indexed by a reduced sleep efficiency, a reduced EEG power density in low delta frequencies and enhanced power density in the frequency range of sleep spindles. To further investigate the role of adenosine in sleep regulation we administered 200 mg of caffeine at 07.10 h and analyzed the sleep stages and EEG power spectra during the subsequent night in nine healthy men. Caffeine levels in saliva decreased from a maximum of 17 mumol/l one hour after intake, to 3 mumol/l immediately prior to the sleep episode starting at 23.00 h. Compared to placebo, sleep efficiency and total sleep time were significantly reduced. EEG power density in nonREM sleep was suppressed in the 0.25-0.5 Hz band and enhanced in the frequency range of sleep spindles (11.25 12.0 Hz and 13.25-14.0 Hz). In REM sleep EEG power density was suppressed in the frequency range of 0.75-4.5 and 5.25-6.0 Hz. The data indicate that a saliva level of caffeine as low as 3 mumol/l directly affects sleep propensity or, alternatively, that the presence of caffeine in the central nervous system during the waking episode reduces the progressive increase of sleep propensity associated with wakefulness. PMID- 7796155 TI - Complement C1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease. AB - C1 inhibitor was identified in human brain tissue by Western blotting and by immunohistochemistry using multiple antibodies to the native protein. The presence of C1 inhibitor mRNA was identified by reverse transcriptase-polymerase chain reaction analysis of brain mRNA extracts. The mRNA was also detected in cultured postmortem human microglia and in the IMR-32 human neuroblastoma cell line. Immunohistochemically, the native protein was detected in residual serum of capillaries and pyramidal neurons of both control and Alzheimer disease cases, as well as in occasional senile plaques of Alzheimer tissue. The reacted protein was detected on dystrophic neurites and neuropil threads in Alzheimer tissue by 4C3 monoclonal antibody, which recognizes a neoepitope following suicide inhibition. These data indicate that C1 inhibitor, a regulatory molecule controlling multiple inflammatory proteolytic cascades, is produced in normal brain. In Alzheimer disease, C1 inhibitor undergoes a prominent reaction in abnormal neuronal processes, such as dystrophic neurites and neuropil threads. PMID- 7796156 TI - Gonadal steroid hormone-dependence of beta-endorphin-like immunoreactivity in the medial preoptic area of the rat. AB - Gonadal steroid hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and gonadal steroid hormone-dependent. Although beta endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of gonadal hormones on the distribution and density of beta Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of gonadal steroid hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally gonadal steroid hormone dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though gonadal hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling. PMID- 7796158 TI - Psychophysiological stress induces heat shock cognate protein (HSC) 70 mRNA in the cerebral cortex and stomach of rats. AB - Families of 70 kDa heat shock proteins have essential roles in cellular coping to noxious stimuli. However, their roles in psychophysiological stress have not been precisely clarified. We tested our hypothesis that heat shock cognate protein (HSC)70 messenger RNA would increase in stress-vulnerable organs under psychophysiological stress. In control rats, cerebral HSC70 mRNAs were constitutively expressed while gastric HSC70 mRNAs were scarcely identified. Restraint-water immersion stress significantly increased the level of cerebral HSC70 mRNAs for 6 h and 12 h. Stress for 6 h with recovery for 6 h induced more gastric HSC70 mRNA levels than that without recovery, while stress for 12 h expressed the highest gastric HSC70 mRNA levels. Hypothermia, induced by water immersion, excluded a possible role of hyperthermia in inducing HSC70 mRNA. Our results point to a crucial cytoprotective role for families of heat shock proteins in stress-vulnerable brain-gut link in mammals under psychophysiological stress. PMID- 7796157 TI - Brain corticotropin-releasing factor mediates 'anxiety-like' behavior induced by cocaine withdrawal in rats. AB - Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse. PMID- 7796160 TI - On the cellular localization and distribution of carbonic anhydrase II immunoreactivity in the rat brain. AB - Evidence is provided that carbonic anhydrase-II is localized in the central nervous system to wide spread systems of oligodendrocytes and restricted astroglia populations, involving both fiber bundles and neuropil. It is suggested that CO2 formed in activated axons may, via carbonic anhydrase-II, give rise to protons controlling the excitability of surrounding neuropil. Thus, CO2 may represent an important, highly diffusible, signal in brain, involved in the tonic control of neuronal activity. PMID- 7796159 TI - Demonstration of parathyroid hormone-related protein in meninges and its receptor in astrocytes: evidence for a paracrine meningo-astrocytic loop. AB - In contrast to the nervous and glial tissue of the adult rat brain the meninges are immunoreactive for parathyroid hormone-related protein (PTHrP), a hormone that binds with high affinity to the recently cloned PTH/PTHrP receptor. Accordingly immunoreactivity is found in cultured meningeal cells but not in astrocytes. In contrast, astrocytes but not meningeal cells synthesize the mRNA for the PTHrP receptor shown by reverse transcription of total RNA preparations and subsequent polymerase chain reaction with primers specific for the PTHrP receptor. The expression of the PTH/PTHrP receptor was confirmed by the dose dependent activation of the adenylate cyclase in astrocytes and the rapid development of cellular processes following on incubation with PTHrP. We conclude that PTHrP secreted by meninges forms a paracrine meningo-astrocytic loop and may cause astrocytic differentiation, possibly involved in the formation of the glial limiting membrane. PMID- 7796161 TI - Synaptic organization of excitatory and inhibitory boutons associated with spinal neurons which project through the dorsal columns of the cat. AB - The cell bodies and proximal dendrites of postsynaptic dorsal column neurons were examined for synaptic boutons which displayed immunoreactivity for the principal excitatory and inhibitory neurotransmitters, glutamate and GABA. The neurons were labelled by retrograde transport of horseradish peroxidase and GABA or glutamate containing boutons were revealed by performing postembedding immunogold reactions on electron microscope sections. Five neurons were examined and all of them were postsynaptic to boutons which contained either GABA or glutamate. Quantitative analysis of two of the cells revealed that more than 90% of the synaptic profiles associated with them displayed immunogold reactions for these transmitters. Analysis of series of alternate sections, which were reacted for either GABA or glutamate, showed that there was no overlap in the populations of immunoreactive boutons. Furthermore, GABA and glutamate immunoreactions were associated with boutons which had different morphological characteristics. In addition, some large glutamate-enriched boutons were postsynaptic to small boutons which displayed immunogold reactions for GABA. This study demonstrates morphological bases for direct excitation, postsynaptic inhibition and presynaptic inhibition of postsynaptic dorsal column cells. PMID- 7796162 TI - The hyper-reinnervation of rat skeletal muscle. AB - This study examines muscle recovery and related changes in the motor unit population of 'hyper-reinnervated' rat skeletal muscle. Medial gastrocnemius (MG) muscles were hyper-reinnervated by either cutting the MG nerve and implanting it on the MG muscle together with additional hind limb nerves, or by crushing the MG nerve and excising the medial portion (50-70%) of the MG muscle. Our findings were that muscles hyper-reinnervated with multiple nerves recovered muscle mass and strength more fully than did the self-reinnervated muscles, more motor units were formed (up to three times the normal number were found), and the mean motor unit size was significantly smaller. A relatively small percentage of muscle fibers became polyneuronally innervated. In contrast, the number of motor units that were formed in the muscle reduction experiments were not significantly larger than was expected considering the mass of the muscles. We conclude that hyper-reinnervation improves muscle recovery, it may be a useful technique for improving function in denervated muscle, and may serve to provide added sources of EMG control signals in some amputees. PMID- 7796163 TI - Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ETA receptors. AB - Central endothelin (ET) has been implicated in the regulation of the cardiovascular system. The effect of intracerebroventricular (i.c.v.) administration of ET-1 or IRL 1620 (5, 15 and 45 ng) on the systemic hemodynamics and regional circulation was studied in anesthetized rats using a radioactive microsphere technique. Systemic hemodynamics and regional blood circulation were determined before (baseline) and at 30 min after the injection of each dose of ET 1 or IRL 1620. Administration of saline (5 microliters, i.c.v.) did not produce any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and regional blood circulation. However, the higher dose (45 ng) produced a transient rise (26%) followed by a sustained fall (48%) in BP. The decrease in BP was accompanied by significant decreases in CO (44%) and SV (39%), while HR and TPR were not affected. ET-1 (45 ng, i.c.v.) also produced a significant reduction in blood flow to the brain (75%), heart (49%), kidneys (66%), GIT (40%), portal system (52%) and musculo-skeletal system (38%), while blood flow to the skin was not affected. To determine pharmacological specificity of the central effects of ET-1, studies were performed in rats pretreated with BQ-123, a specific ETA receptor antagonist. Pretreatment with BQ-123 (10 micrograms, i.c.v.), 15 min prior to the administration of ET-1, completely antagonized the systemic hemodynamic as well as the regional circulatory effects of ET-1 (45 ng, i.c.v.). In order to determine whether stimulation of central ETB receptors produces any cardiovascular effects, studies were performed using IRL 1620, a specific ETB receptor agonist. Administration of IRL 1620 (5, 15 and 45 ng, i.c.v.) did not produce any effect on systemic hemodynamics and regional blood circulation in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET. PMID- 7796164 TI - Adrenocorticotropin secretagog release: stimulation by frustration and paradoxically by reward presentation. AB - Colchicine blockade of axonal transport from the paraventricular nucleus to the median eminence was used to indirectly infer adrenocorticotropin (ACTH) secretagog release in response to a reward presentation and the psychological stressor of frustration. After training rats to drink at the same time of day for 30 min for 2-3 weeks, basal arginine vasopressin (AVP), but not corticotropin releasing factor (CRF) or oxytocin (OT), concentrations were elevated. The frustration of presenting empty water bottles resulted in increased corticosterone concentrations. Concordantly, CRF, AVP, and OT contents in the median eminence decreased compared to controls. All three secretagogs are thus apparently involved in the corticosterone response to frustration. As expected, water presentation decreased both ACTH and corticosterone. Paradoxically, however, CRF, AVP, and OT contents also decreased compared to controls. The discrepancy of ACTH and corticosterone concentrations declining despite release of secretagogs cannot be explained by decreased adrenal or pituitary sensitivities since both exogenous ACTH and CRF elevated corticosterone and ACTH, respectively, in rewarded rats. Secretagog release, therefore, may not always be associated with stimulation of ACTH release. PMID- 7796165 TI - The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain. AB - We have examined the distribution of 5-HT1A and 5-HT2A receptor mRNAs in post mortem human hippocampus, neocortex, raphe nuclei, cerebellum and basal ganglia using in situ hybridization histochemistry. Receptor transcripts in brains from two males and two females (mean age +/- S.D. = 70 +/- 4 years; post-mortem interval = 29 +/- 6 h) were visualised with 35S-radiolabelled synthetic oligodeoxyribonucleic acid probes. In the hippocampus, 5-HT1A receptor mRNA was present in all fields, especially CA1. In the parahippocampal gyrus and neocortical regions 5-HT1A receptor mRNA was enhanced in superficial and middle laminae. 5-HT1A receptor mRNA was particularly abundant in the raphe and other serotonergic cell groups of the brainstem. The analysis of emulsion dipped sections showed 5-HT1A receptor mRNA to be concentrated in pyramidal neurons, together with the granule cells of the dentate gyrus. In neocortical areas lamina III pyramidal neurons were more heavily labelled than those in lamina V. There was no evidence of glial expression of 5-HT1A receptor mRNA in grey matter or white matter compartments. 5-HT2A receptor mRNA was present in all neocortical areas examined, where it was located in pyramidal neurons, of lamina V more than in those of lamina III, as well as in putative interneurons, especially within lamina IVc of the striate cortex. 5-HT2A receptor mRNA was observed at minimal levels in the hippocampus and not in the raphe. Neither 5-HT1A nor 5-HT2A receptor mRNA were detected in the cerebellum, substantia nigra or striatum. The ability to detect these transcripts at the regional and cellular level will help reveal important details of the 5-HT receptor system in the human brain. This includes the investigation of their putative roles in the normal chemoarchitecture and in pathophysiological brain processes. PMID- 7796166 TI - Tongue adaptation temperature influences lingual nerve responses to thermal and menthol stimulation. AB - Menthol, a tangible substance present in many orally administered products, can produce a powerful influence on the perceived intensity of subsequent thermal stimulation in humans as well as the response magnitudes of thermally sensitive neurons in rats. However, there are no prior studies examining the influence of adaptation temperature on perceived intensity and/or response magnitudes of thermally sensitive neurons to subsequent menthol stimulation. We identified 32 thermally sensitive neurons that increased their discharge rate to a gradual temperature decrement beginning from 35 degrees C and dropping to 10 degrees C at 1 degree C/s. Based on their response threshold, time-to-peak, and range of sensitivity, these thermally sensitive lingual neurons were found to be divisible into two distinct groups. Group 1 neurons (n = 21) responded best to the upper cool range (34-15 degrees C) of the temperature decrement, whereas Group 2 neurons (n = 11) responded to the lower cold range (32-10 degrees C) of the temperature decrement. Our Group 1 and Group 2 neurons may be analogous to low threshold and high threshold cold receptors identified previously in primates. We also examined the responses of lingual neurons to 0%, 25%, 50% and 75% dilution's of a stock menthol concentration (1.28 mM) at 25 and 35 degrees C adaptation temperatures. Menthol responses across all concentrations were far larger after adaptation to 35 degrees C compared to 25 degrees C. Furthermore, only during 35 degrees C adaptation did responses to menthol stimulation persist during the ensuing 20 s after menthol off-set and water on-set.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796168 TI - Muscimol injected into the right or left amygdaloid complex differentially affects retention performance following aversively motivated training. AB - The effects of intra-amygdala infusion of the GABAA agonist, muscimol, prior to retention testing was examined. In Expt. 1, rats were trained in a one-trial inhibitory-avoidance task and given bilateral intra-amygdala infusions of vehicle or muscimol or simultaneous unilateral infusions of each, 5 min before the retention test 24 h after training. Expt. 2 used the same procedures as those in Expt. 1 but two retention measures were taken: initial step-through latency and the number of trials to reach criterion during continuous multiple-trial inhibitory-avoidance (CMIA) training. Groups given bilateral infusions of muscimol or unilateral infusion of muscimol into the right amygdala had significantly shorter latencies to enter the dark compartment than groups given bilateral infusions of vehicle or unilateral infusion of muscimol into the left amygdala. Bilateral muscimol infusions impaired acquisition of CMIA relative to bilateral vehicle infusions or unilateral muscimol infusion into the left amygdala. These results suggest differential involvement of the right and left amygdala in memory. PMID- 7796169 TI - Enhanced nociceptive behaviour following conditioning injection of formalin in the perioral area of the rat. AB - The possible existence of long-term modifications in response to a transient nociceptive conditioning stimulation was investigated in the rat in three experiments. (1) A nociceptive conditioning stimulus was delivered in the form of a s.c. formalin injection (conditioning injection) in the left upper lip. Evaluation of the nociceptive behaviour triggered by another formalin injection (testing injection) made in the controlateral right upper lip was carried out in distinct groups of rats 7, 14 or 28 days after the conditioning. An enhanced nociceptive response at day 7 and 14 and a return to the baseline at day 28 were observed. (2) A similar protocol was developed with formalin used for both conditioning and testing but an anaesthetic blockade of the infraorbital nerve was performed just before the conditioning injection to suppress the initial barrage. The change observed at day 7 was suppressed by the nerve block. (3) A conditioning nociceptive stimulus was applied either ipsilaterally to the right lower lip or to the tail. An increased nociceptive response was observed when the conditioning stimulus was applied to the same side as the test stimulus but no increase in the formalin test response was detected when the conditioning stimulus was applied to the tail. These results indicated that, after a single formalin injection in the left upper lip, a hyperexcitability developed that depended on the initial barrage, lasted for at least 2 weeks, was no longer present at 4 weeks and might rely on a segmental mechanism. The hypothesis of a central sensitization triggered by an initial barrage and maintained by an ongoing input induced from the periphery is discussed. PMID- 7796170 TI - Induction of the immediate early gene c-jun in human spinal cord in amyotrophic lateral sclerosis with concomitant loss of NMDA receptor NR-1 and glycine transporter mRNA. AB - The aetiology of the sporadic form of amyotrophic lateral sclerosis (ALS) is poorly understood although abnormalities in glutamate and glycine transport have been implicated which both could contribute to a neurodegenerative process mediated through the N-methyl-D-aspartate (NMDA) receptor. In this study we have used in situ hybridization to investigate whether any changes in the expression of NMDA receptors, the glycine transporter or glutamate-mediated injury responses are detectable in ALS. Two immediate early genes were investigated as markers of neuronal injury responses, c-jun and zif-268, both constitutively expressed in the spinal cord. Levels of c-jun mRNA were most abundant in intermediate grey and layer IX of the ventral horn containing motor neurones. This pattern was markedly changed in ALS with large increases (2-3 fold) in c-jun mRNA occurring in dorsal and ventral horn. The marked increase in c-jun mRNA was also substantiated by slot blot analysis of tissue homogenates of spinal cord and a parallel induction of zif-268 mRNA was also seen. NMDA receptor NR-1 mRNA was widely distributed in control spinal cord with the highest concentrations occurring in layers IX, X, intermediate grey and dorsal horn. The ALS cases showed a selective decrease in the level of NR-1 mRNA in the ventral region (50%) whilst no significant decrease was detected in the dorsal region. Quantitation of tissue homogenates with dorsal and ventral regions combined also yielded a significant decrease of 40% which supports the analysis from in situ hybridization densitometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796171 TI - Neuroprotective effects of PKC inhibition against chemical hypoxia. AB - The effect of potassium cyanide-induced chemical hypoxia on protein kinase C (PKC) translocation and cell injury was studied in differentiated PC12 cells. The cellular distribution of PKC in control cells and cells exposed to 100 microM and 1 mM KCN for 30 min. was visualized by use of an anti-PKC antibody and confocal laser scanning microscope. In control differentiated PC12 cells, PKC was localized perinuclearly, while following 12-phorbol 13-myristate acetate (PMA) or KCN it was translocated to the plasma and organelle membranes. Western blot analysis was used to quantify the translocation. Chemical hypoxia increased the membrane-bound PKC to 210% of control levels, while chelerythrine, a PKC inhibitor, and block of calcium influx into the cells (with calcium channel blocker and calcium-free medium) prevented this effect. Cyanide-induced PKC translocation persisted for at least 120 min. Cell injury was monitored by measuring lactate dehydrogenase (LDH) efflux from the cells 24 hr after addition of cyanide. PKC activation plays a role in hypoxic damage, since PKC down regulation (by overnight exposure to PMA) or inhibition (with chelerythrine or staurosporine) conferred protection against KCN-induced cytotoxicity. Ca2+ channel blocker nifedipine also protected against chemical hypoxia. None of the pretreatments rendered complete protection against cyanide-induced hypoxia, indicating that PKC-independent mechanism(s) are also activated during chemical hypoxia and contribute to cell injury. PMID- 7796172 TI - Succinate dehydrogenase activity and soma size relationships among cat dorsal root ganglion neurons. AB - A large range in succinate dehydrogenase (SDH) activity and soma size among neurons in the dorsal root ganglion (DRG) and the dorsolateral region of the ventral horn (DLVH) at spinal cord level L7 was observed. Mean soma sizes were similar for the two populations. DLVH, but not DRG, neurons showed an inverse relationship between SDH activity and soma size. DRG neurons had a higher mean SDH activity than DLVH neurons, reflecting the observation that there was a population of DRG neurons with a higher oxidative capacity than DLVH neurons. PMID- 7796167 TI - Effects of dehydration and salt-loading on hypothalamic vasopressin mRNA level in male and female rats. AB - Experiments were carried out on 9- to 11-week-old male and female Sprague-Dawley rats. Dot-blot analysis and 3'-end digoxigenin-labeled 26mer oligonucleotide probe were used in the investigation of vasopressin (AVP) mRNA level in the hypothalamus of male and female rats. The normal hypothalamic AVP-mRNA level in males was 48% higher than that in females (P < 0.05). Plasma osmolality was also higher in males than in females (P < 0.05). In dehydrated rats, the hypothalamic AVP-mRNA level was 2.47 and 1.98 times in females (P < 0.001) and males (P < 0.01), respectively, as much as in their normal controls; the difference in hypothalamic AVP-mRNA level between dehydrated females and males was statistically insignificant. Plasma osmolality was higher in dehydrated females than in dehydrated males (P < 0.01). In salt-loaded rats, hypothalamic AVP-mRNA level was 2.47 and 2.17 times in females (P < 0.001) and males (P < 0.01), respectively, as much as in their controls. The difference in hypothalamic AVP mRNA level between salt-loaded males and females was not statistically significant. Plasma osmolality in salt-loaded females was also higher than that in salt-loaded males (P < 0.001). These findings indicate that there is sex difference in hypothalamic AVP mRNA level and plasma osmolality under normal conditions; during dehydration and salt-loading AVP mRNA level increases and the difference in AVP mRNA level between males and females becomes insignificant. PMID- 7796173 TI - Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. AB - The amyloid beta-peptide (A beta) that accumulates as insoluble plaques in the brains of Alzheimer's victims can be neurotoxic, by a mechanism that may involve generation of reactive oxygen species (ROS) and destabilization of cellular calcium homeostasis. We now provide evidence that the mechanism of neurotoxicity of two other amyloidogenic peptides (APs), human amylin and beta 2-microglobulin, also involves induction of ROS and elevation of [Ca2+]i. Human amylin, beta 2 microglobulin and A beta 1-40 all caused significant death of neurons in rat hippocampal cell cultures during 24-48 h exposure periods. Rat amylin, a non-AP, was not neurotoxic. Each AP caused an elevation of rest [Ca2+]i during a 20 h exposure period, and promoted a sustained elevation of [Ca2+]i following exposure to glutamate which was significantly greater than controls. Each AP induced accumulation of ROS in neurons which preceded elevation of [Ca2+]i. Several antioxidants, including propyl gallate, vitamin E and the spin-trapping compound N-tert-butyl-alpha-phenylnitrone attenuated the elevation of [Ca2+]i and neurotoxicity induced by the peptides. The data indicate that different APs share a common mechanism of neurotoxicity involving free radical accumulation and destabilization of [Ca2+]i homeostasis. PMID- 7796174 TI - Secretion and accumulation of Alzheimer's beta-protein by cultured vascular smooth muscle cells from old and young dogs. AB - Cultured smooth muscle cells isolated from beta-amyloid-affected blood vessels from old dogs accumulate beta-protein at early passages [5,24]. Now, we show that smooth muscle cells derived from amyloid-free brain blood vessels and peripheral arteries from old and young animals are induced by culture conditions to deposit intracellularly fibrillar and non-fibrillar beta-protein. Accumulation of beta protein is associated with a higher secretion of beta-protein, but not with a higher secretion of beta-amyloid precursor protein (beta APP) or higher cellular content of beta APP. Gradual cessation of proliferative activity was observed in cultures that accumulate beta-protein. PMID- 7796175 TI - Asymmetrical motor behavior in rats with unilateral striatal excitotoxic lesions as revealed by the elevated body swing test. AB - Severe degeneration of basal ganglia neurons, particularly the intrinsic neurons of the striatum, is the major underlying neuropathology implicated in clinical attributes of Huntington's disease (HD). The excitotoxin-lesioned striatum provides a useful model for evaluating behavioral parameters of HD. Animals with unilateral excitotoxic lesions exhibit asymmetrical rotational behavior in response to dopamine agonists, such as apomorphine. However, the observed behavior is a pharmacological reaction, and subject to sensitization effects. A behavioral test using undrugged animals may demonstrate a more natural response of the animals to the lesion effects. Recently, we have developed the 'drug-free' elevated body swing test (EBST), and demonstrated that hemiparkinsonian rats exhibited significant biased swing activity. In the present study, we observed that animals with unilateral intrastriatal 3-nitropropionic acid or quinolinic acid lesions displayed a significant biased swing activity with the direction ipsilateral to the lesioned side of the brain. This ipsilateral swing corresponded to the ipsilateral rotational behavior exhibited by the lesioned animals when challenged with apomorphine. The present results demonstrated that the EBST is a sensitive measure for characterizing asymmetrical behavior in animals with striatal lesions. PMID- 7796176 TI - Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS). AB - Two different lines of mice, G1 and G20, carrying a transgene for a mutant form of Cu,Zn SOD, found in a family with familial amyotrophic lateral sclerosis (FALS), develop clinical and pathological changes which are, in their late stages, strikingly similar to those in human disease. We have analyzed the distribution and characteristics of lesions in the central and peripheral nervous systems of such mice. The most affected structure was the spinal cord, followed by the medulla, pons and midbrain. The early stages of the disease were characterized by vascular degeneration of anterior horn neurons and their processes, while, in the late stages, the main changes consisted of neuronal loss and atrophy of the anterior horns and the deposition in these areas of multiple filamentous inclusions resembling Lewy bodies. In the late stages of the disease, the white matter of the spinal cord was also involved, particularly in the anterior and lateral columns. Posterior columns were also involved, but to a much lesser degree. The brainstem structures also showed vacuolar degeneration of several motor nuclei and of several groups neurons in the reticular formation. Anterior roots and peripheral nerves showed the classical features of Wallerian degeneration. The dorsal root ganglia, with rare exceptions, were unremarkable. The posterior roots showed mild changes in the most severely affected mice. Changes in these two affected lines were compared to changes in mice overexpressing wild type, rather than mutant human Cu,Zn SOD. These mice never developed clinical disease, although, pathologically, they developed very mild vacuolar changes in the anterior horns of the spinal cord and in motor axons. This study shows that although simple overexpression of SOD may be injurious to motor neurons, albeit very mildly, the mutant form is necessary to produce both clinical disease and severe pathological changes which, in the chronic stage of the disease, have striking similarities to human familial ALS. A dominant gain of function, therefore, is the most likely pathogenesis of tissue injury induced by mutations in Cu,Zn SOD. PMID- 7796177 TI - Differential distribution of protein kinase C (PKC alpha beta and PKC gamma) isoenzyme immunoreactivity in the chick brain. AB - Protein kinase C (PKC) is involved in neural plasticity. The phosphorylation of the myristoylated alanine-rich protein kinase C substrate (MARCKS) in the left intermediate and medial hyperstriatum ventrale (IMHV) of the chick brain has been shown previously to correlate significantly with the strength of learning in filial imprinting. The distribution of PKC alpha, beta I, beta II and PKC gamma in the brain of 1-day-old dark-reared chicks was determined immunocytochemically, using the monoclonal antibodies MC5 and 36G9, raised against purified PKC alpha beta and PKC gamma, respectively. PKC gamma-stained cells were distributed widely in the telencephalon, including all hyperstriatal structures (including the IMHV), the hippocampus, neostriatum, ectostriatum and archistriatum. There were fewer stained cells in the septum and the least cellular staining was in the paleostriatum primitivum. Fluorescent double-labelling with neuron-specific enolase (NSE) and with the glial calcium-binding protein S100 suggested that PKC gamma immunoreactivity was present in neurones but not in glia. The distribution of PKC alpha beta-stained cells was more limited, with staining in the archistriatum, hippocampus and septum but not in the hyperstriatum. However, there was PKC alpha beta-staining of some fibres in the IMHV (but little elsewhere in the hyperstriatum ventrale), in the neostriatum, paleostriatal complex and the lobus parolfactorius. Double-labelling with NSE and S100 revealed PKC alpha beta/S100-positive glial cells present in the paleostriatal region only. There was some PKC alpha beta-staining of putative neurones in the hippocampus, septum and archistriatum. The differential distribution of PKC isoenzymes suggests that in the IMHV some axonal inputs contain PKC alpha beta whereas some postsynaptic cells contain the gamma form of PKC. PMID- 7796178 TI - Protein kinase C in the hippocampus is altered by spatial but not cued discriminations: a component task analysis. AB - The exact role of the mammalian hippocampus in memory formation remains essentially as an unanswered question for cognitive neuroscience. Experiments with humans and with animals indicate that some types of mnemonic associative processes involve hippocampal function while others do not. Support for the spatial processing hypothesis of hippocampal function has stemmed from the impaired performance of rats with hippocampal lesions in tasks that require spatial discriminations, but not cued discriminations. Previous procedures, however, have confounded the interpretation of spatial versus cued discrimination learning with the number and kinds of irrelevant stimuli present in the discrimination. An empirical set of data describing a role of protein kinase C (PKC) in different mnemonic processes is similarly being developed. Recent work has implicated the activation of this serine-threonine kinase in a variety of learning paradigms, as well as long-term potentiation (LTP), a model system for synaptic plasticity which may subserve some types of learning. The present study employs the principles of component task analysis to examine the role of membrane associated PKC (mPKC) in hippocampal-dependent memory when all factors other than the type of learning were equivalent. The results indicate that hippocampal mPKC is altered by performance in hippocampally-dependent spatial discriminations, but not hippocampally-independent cued discriminations and provide a general experimental procedure to relate neural changes to specific behavioral changes. PMID- 7796179 TI - Electrophysiological characterization of the inhibitory effect of a novel peptide gurmarin on the sweet taste response in rats. AB - The effect of an anti-sweet peptide, gurmarin purified from the leaves of Gymnema sylvestre, was studied electrophysiologically on taste responses of the rat chorda tympani. The action of gurmarin was highly specific to sweet taste so that responses to various sweeteners including sugars, sweet amino acids and an artificial sweetener, saccharin were all suppressed. The most effective pH at which the rat tongue was treated with gurmarin was found to be 4.5, which corresponds to the isoelectric point of the peptide. At this condition about 5 microM of gurmarin was sufficient to reveal maximal effect and this was still significant at 0.5 microM (2 micrograms/ml). Although the suppressed responses required several hours to attain complete recovery, anti-gurmarin serum shortened the recovery time considerably. On the other hand, intravenous injection of gurmarin did not cause any significant effects on taste responses at all. These results suggest that gurmarin acts on the apical side of the taste cell, possibly by binding to the sweet taste receptor protein. PMID- 7796180 TI - SPARC, an extracellular matrix glycoprotein containing the follistatin module, is expressed by astrocytes in synaptic enriched regions of the adult brain. AB - Although extracellular matrix (ECM) glycoproteins play important roles in neural development, their levels are generally believed to decrease in the adult brain. Immunohistochemical analysis indicates that the anti-adhesive ECM glycoprotein SPARC/osteonectin, which contains a follistatin 'module,' is expressed in the adult rabbit nervous system. In the cerebellum, SPARC is present in Bergmann glia, with a strong signal along their radial fibres. SPARC, while enriched in membrane fractions, is not a transmembrane protein. In the hippocampus, colocalization of SPARC is observed in cells which express the astrocytic marker GFAP. The expression of SPARC by a subset of astrocytes, particularly in synaptic enriched areas, suggests a continuing role for the ECM in the adult brain. PMID- 7796181 TI - Immunolocalisation of protein phosphatase inhibitor-1 in the cerebral cortex of the rat, cat and ferret. AB - The distribution of inhibitor-1 was analysed in the neocortex of cat, ferret and rat by immunocytochemistry (at the light and electron microscope levels) and by immunoblotting using an affinity purified antibody which recognises both the phosphorylated and dephosphorylated forms of the protein. In each mammalian cortex immunocytochemical techniques identified inhibitor-1 predominantly in infragranular pyramidal neurons and, at a lower concentration, in supragranular pyramidal neurons of cortical layers II-III, and V-VI. Within the cortical layers, neuronal cell bodies and apical dendrites were stained strongly but no immunoreactivity was associated with dendritic spines. Regional differences in intensity of staining were revealed when appropriate antibody concentrations were used; the concentration of inhibitor-1 appeared to follow a gradient with the highest levels in layer VI and the lowest in layer I. The results were confirmed by immunoblotting of microdissected cortical regions which identified the inhibitor-1 protein unambiguously. The distribution of inhibitor-1 is different from that reported by other investigators. PMID- 7796182 TI - Pharmacology of selective and non-selective metabotropic glutamate receptor agonists at L-AP4 receptors in retinal ON bipolar cells. AB - Retinal ON bipolar cells possess metabotropic glutamate receptors (mGluRs) which are sensitive to L-2-amino-4-phosphonobutyric acid (L-AP4). Recent studies suggest there are multiple subtypes of L-AP4 receptors. In order to provide a more complete description of the pharmacology of the retinal L-AP4 receptor, we examined the actions of a number of compounds which are active at L-AP4 receptors and other mGluRs. Four groups of compounds were studied: (1) AP4 analogues (e.g. L-AP5, L-SOP, cyclobutylene AP5, and N-Me-AP4), (2) non-selective mGluR agonists (ibotenate and quisqualate), (3) selective mGluR agonists (L-CCG-I), and (4) agonists proposed to be selective for specific mGluR subtypes (DCG-IV and t-ADA). Concentration-response curves were obtained using the b-wave of the electroretinogram (ERG) as an assay for L-AP4 receptor activation. Whole cell voltage clamp recordings from ON bipolar cells in the retinal slice preparation of the mudpuppy were used to determine whether the compounds acted as L-AP4 receptor agonists. All compounds were L-AP4 receptor agonists, except t-ADA which was ineffective. The results reveal pharmacological differences between L-AP4 receptors in mudpuppy ON bipolar cells and those in other systems, consistent with the proposal that there are multiple L-AP4 receptor subtypes. For example, retinal L-AP4 receptors are more potently activated by L-AP5 than L-SOP, whereas L-SOP has been shown to be more potent than L-AP5 in L-AP4 receptors in the lateral perforant path (LPP) of the rat hippocampus. L-SOP is also relatively more potent at the cloned L-AP4 receptors mGluR4, 6, and 7 than in mudpuppy ON bipolar cells in situ. The different potencies of these compounds in retina and LPP is ascribed to both steric and charge factors. The results with DCG-IV and t ADA are consistent with the proposal that these are subtype-selective agonists, but DCG-IV is likely to be selective only at very low concentrations (< or = 1 microM). PMID- 7796183 TI - Patients' rights in hospital: an empirical investigation in Finland. AB - The purpose of this study was to examine patients' rights in Finnish hospitals from the patients' own points of view. In 1993, a new Act on the status and right of patients in health care came into force. In this Act patients' rights are divided into three categories: the right to good health care, the right to be informed, and the right to self-determination and participation. These same categories of rights were used in this empirical investigation during 1993, in which a questionnaire was answered by 204 patients in two Finnish hospitals. The results indicate that Finnish hospital patients do not know enough about their rights. Information seems to be one of the most problematic areas for hospital patients. The study will be repeated in five years' time. PMID- 7796185 TI - Ethical dilemmas in the lived experience of nursing practice. AB - Through a series of semistructured interviews with 12 nurses delivering direct patient care in acute, long-term and home care settings, information was sought regarding the ethical concerns of practicing nurses. Although these nurses frequently did not specifically identify the areas of expressed concern as ethical in nature, thematic analysis of the transcribed interviews uncovered four major ethical areas of concern common to these 12 nurses. These areas are: (1) Withholding of information and truth-telling; (2) Unequal access or inequalities in care; (3) Differences between business and professional values; (4) Breaking and reporting broken rules. Several reasons are offered to explain the failure of nurses accurately to identify specific practice dilemmas as ethical in nature and the sequelae of these failures. Possibilities involving ongoing education and mentored experiences in practice areas are reported. PMID- 7796184 TI - Nursing home staff attitudes to ethical conflicts with respect to patient autonomy and paternalism. AB - Six case studies on nursing home staff attitudes to patient autonomy have been analysed. The case studies are based on six polarities within autonomy, as developed by Collopy. In total, 189 professional caregivers, comprising the staff of 13 nursing homes in the county of Stockholm, Sweden, responded to questions based on the case studies. Results show that the attitudes within each professional category had a high level of internal correspondence. Nurses consistently supported patient preferences to the highest degree, followed by assistant nurses and auxiliary staff. Nurses' aides ranked lowest in supporting patient preferences. In only one of the cases were background variables of significance. PMID- 7796186 TI - Comprehensive patient-family care: fact or fiction? AB - The ICN 1973 Code for nurses states that 'Nurses render health services to the individual, the family and the community...'. It goes on to say that, 'The nurse's primary responsibility is to those people who require nursing care.' Thus, our primary responsibility to provide comprehensive care to patients and their families is a concept we teach and preach, but can it be achieved? In this paper, I would like to present the ethical dilemmas expressed by nurses as inherent in the care of patients and their families, address the difficulties in treating patients and their families in the light of these dilemmas and propose a different approach to dealing with the problem. PMID- 7796187 TI - Best interests: a concept analysis and its implications for ethical decision making in nursing. AB - The purpose of this paper is to analyse the concept of 'best interest' in order to give nurses, who use it to justify their actions, a clear picture of what this means, and to identify the skills needed for doing so. The process for concept analysis developed by Walker and Avant was used in the analysis of data generated from the literature. Themes were identified from which the defining attributes, antecedents and consequences emerged. The congruence of the findings with current values in nursing, such as promotion of patient autonomy, and the nurse as advocate, are discussed, together with the underpinning ethics theory. The skills needed for nursing practice are identified and recommendations for nurse education are made. PMID- 7796189 TI - Professional nurses should have their own ethics: a response. PMID- 7796190 TI - Rights to minimal standards of quality and courtesy. PMID- 7796192 TI - International Conference on Women's Health: Occupation and Cancer. III. Proceedings. Baltimore, Maryland, November 1993. PMID- 7796188 TI - Suicide and voluntary active euthanasia: why the difference in attitude? AB - It appears that the attitudes of health professionals differ towards suicide and voluntary active euthanasia. An acceptance of, if not an agreement with, voluntary active euthanasia exists, while there is a general consensus that suicide should be prevented. This paper searches for a working definition of suicide, to discover ethical reasons for the negative value that suicide assumes, and also to provide a term of reference when comparing suicide with euthanasia. On arriving at a working definition of suicide, it is compared with voluntary active euthanasia. An analysis of utilitarian and deontological considerations is provided and proves to be inconclusive with respect to the ethical principles informing the attitudes of professionals. Therefore, a search for other influences is attempted; this indicates that psychological influences inform attitudes to a greater degree than ethical principles. PMID- 7796191 TI - Medical and nursing ethics: never the twain? AB - Since the publication of Carol Gilligan's In a different voice in 1982, there has been much discussion about masculine and feminine approaches to ethics. It has been suggested that an ethics of care, or a feminine ethics, is more appropriate for nursing practice, which contrasts with the 'traditional, masculine' ethics of medicine. It has been suggested that Nel Noddings' version of an 'ethics of care' (or feminine ethics) is an appropriate model for nursing ethics. The 'four principles' approach has become a popular model for medical or health care ethics. It will be suggested in this article that, whilst Noddings presents an interesting analysis of caring and the caring relationship, this has limitations. Rather than acting as an alternative to the 'four principles' approach, the latter is necessary to provide a framework to structure thinking and decision making in health care. Further, it will be suggested that ethical separatism (that is, one ethics for nurses and one for doctors) in health care is not a progressive step for nurses or doctors. Three recommendations are made: that we promote a health care ethics that incorporates what is valuable in a 'traditional, masculine ethics', the why (four principles approach) and an 'ethics of care', the 'how' (aspects of Noddings' work and that of Urban Walker); that we encourage nurses and doctors to participate in the 'shared learning' and discussion of ethics; and that our ethical language and concerns are common to all, not split into unhelpful dichotomies. PMID- 7796193 TI - Women in the public sector: cancer mortality. AB - Very few mortality occupational studies of female workers have been published, even though the number of women in the workforce has increased dramatically to reach more than 45%. Public sector employees comprise 12% of the female workforce. This article reports the findings of a retrospective cohort mortality study of 1371 full-time female employees of the city of Buffalo, New York, who were employed between January 1, 1950, and October 1, 1979, and have worked a minimum of 5 years. The majority of women were hired in the 1940s and early 1950s and began employment after age 30. This predominantly white-collar, service oriented female cohort demonstrated significantly lower all-cause mortality than that expected based on US mortality rates for white females. The highest observed numbers of cancer deaths were for breast, digestive, and respiratory cancers. The majority of person-years were accrued in clerical and service occupations. Higher than-expected mortality was shown for reproductive and respiratory cancers among professional employees; digestive cancers, diseases of the nervous system, and pneumonia among clerical workers; and cancers of the lung and brain and diseases of the digestive system, especially ulcers, among service employees. Because these results are based on few observed cases, they must be interpreted cautiously. PMID- 7796194 TI - Cancer incidence among women in the workplace: a study of the association between occupation and industry and 11 cancer sites. AB - Few studies of the occupational etiology of cancer have focused upon the risks that women experience in the workplace. In this case-referent study of 11 cancer sites (lung, colon, rectum, bladder, esophagus, liver, salivary gland, stomach, eye, melanoma of the skin, mesothelioma), 7686 women in the Detroit area were interviewed to obtain lifetime histories of employment, tobacco use, and adult health, as well as demographic information. The results provide both methodologic and substantive leads for future investigations of the association between women's employment and their risk of cancer. We found that 63% of respondents had a usual occupation of housewife. Methodologic issues are discussed about the implications of this finding for sample size and statistical analysis when conducting such studies. New observations that merit further investigation include an association between salivary gland cancer and employment in hairdressing shops, esophageal cancer and employment in restaurants, and bladder cancer and employment in computer manufacturing. Further research is needed to understand the occupational etiology of cancer among women; such studies must consider specific methodologic issues. PMID- 7796196 TI - Occupation and female papillary cancer of the thyroid. AB - This article presents the joint results of two Swedish case-control studies regarding occupational exposure and female papillary thyroid cancer. Questionnaires inquiring about lifetime occupations and specific occupational exposures were mailed to cases and controls, aged 20 to 70 years. Some 185 female papillary or mixed cancer cases and 426 female controls were included in the analysis. Increased risks were seen for women who had worked as a dentist/dental assistant, teacher, shoemaker, or warehouse worker. In addition, occupational contacts with undefined chemicals, x-rays, or video display terminals were indicated as risk factors. PMID- 7796197 TI - Cancer mortality patterns among women who served in the military: the Vietnam experience. AB - In response to concerns of women veterans regarding the long-term health effects of military service in Vietnam, the Department of Veterans Affairs has been conducting a retrospective cohort mortality study of women Vietnam veterans. Military records were used to identify approximately 4600 women who served in Vietnam between July 4, 1965, and March 28, 1973, and a comparison cohort of nearly 5300 women who served during the same time frame but not in Southeast Asia or the Pacific theater. Current data include vital status determinations as of December 31, 1991, with a total of 532 deaths and an average follow-up of just over 20 years for both groups. Both the Vietnam and non-Vietnam women cohorts had a significant deficit of deaths from all causes compared to women in the US population. The two cohorts showed no difference in total mortality or in deaths from all cancers. A significant excess risk of pancreatic cancer was observed among Vietnam nurses compared to either non-Vietnam nurses (relative risk = 5.74) or women in the US population (standardized mortality ratio (SMR) = 2.78). Vietnam nurses also had an elevated risk of dying from cancer of the uterine corpus. Non-Vietnam nurses had a higher lung cancer mortality rate than women in the general population (SMR = 1.55) or nurses who served in Vietnam. Observed deficits of deaths from all causes and circulatory system diseases generally confirm a healthy selection bias for entry into and retention in the military that has been observed among men serving in the Armed Forces. PMID- 7796198 TI - Cancer incidence among Icelandic nurses. AB - This study investigated cancer incidence among Icelandic nurses, with a special focus on breast cancer. Cancer incidence in the study group was compared with that of the general female population. Elevated standardized incidence ratios (SIRs) were seen for some cancer sites, including breast cancer. For all cancers, breast cancer, and selected cancer sites, SIR increased with increasing length of time intervals allowed to elapse before the study period began. The nurses with a shorter employment time had a higher incidence of cancer than those with a longer one. Known confounding factors--parity and age at first birth--do not appear to be a convincing explanation of the excess of breast cancer. The possibility cannot be excluded that the nursing occupation constitutes an independent risk factor for breast cancer. PMID- 7796195 TI - Occupational risk factors for brain tumors among women in Shanghai, China. AB - The etiology of brain cancer is not well understood and few studies have evaluated occupational risk factors among women. We evaluated occupation and industry at time of diagnosis for 276 incident primary brain tumor cases among women in Shanghai, China, for the period 1980-1984, identified through the Shanghai Cancer Registry. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were calculated for all occupations and industries with at least three female cases. SIRs compared observed to expected numbers of cases, based on incidence rates for Shanghai and the number of women in each occupation and industry according to the 1982 census. Statistically significant excesses of brain tumors were seen among grain farmers (SIR = 6.5, 95% CI = 1.3 19.1), rubber workers (SIR = 5.0, 95% CI = 1.6-11.6), and workers in transportation equipment manufacture and repair (SIR = 2.3, 95% CI = 1.1-4.3). Risks among textile spinners and winders were of borderline significance (SIR = 1.7, 95% CI = 1.0-2.8). Elevated but nonsignificant risks of 2.0 or greater were seen among nurses, plastic products workers, sanitation workers, painters, and workers in manufacture of equipment for electrical generation, transmission, and distribution. Results for farmers, rubber workers, and painters are consistent with previously reported excesses among these occupations in men. The increase among nurses is a new finding, although elevated risks have been observed among male medical professionals. Risks were elevated with likely exposure to pesticides, particularly among those thought to have a high probability and a high level of exposure (SIR = 3.6, 95% CI = 1.2-8.5). PMID- 7796199 TI - Molecular, cytogenetic, and hematologic effects of ethylene oxide on female hospital workers. AB - Women comprise the majority of workers exposed to ethylene oxide during sterilization of medical instruments and supplies. This article evaluates molecular, cytogenetic, and hematologic effects of ethylene oxide on 68 women workers employed in nine hospitals in the United States and one hospital in Mexico. Workers were classified by three exposure categories: none (0), low (> 0 32 ppm-hrs), and high (> 32 ppm-hrs). Hematologic effects were evaluated using complete blood count with differential, which has been questioned as a test for screening ethylene oxide-exposed workers. A statistically significant decrease in hematocrit (n = 0.02) and hemoglobin (P = 0.03) levels, an increase in lymphocyte percentages (P = 0.04), and a relative decrease in neutrophil percentages (P = 0.03) with exposure were observed in US workers. The absolute number of lymphocytes, however, showed no relationship with exposure. No statistically significant results were seen for Mexican workers, although hematocrit decreased with exposure. An exposure-response relationship for the percentage for lymphocytes (positive) and neutrophils (negative) in US subjects and for neutrophils (positive) in Mexican subjects was seen. No overall relation with exposure was observed for total number of white cells. Molecular and cytogenetic results are also reported for the 68 women, who constitute a subgroup from a previous report. US women workers showed a statistically significant exposure response relationship for ethylene oxide and hemoglobin adducts (P = 0.0002) and sister chromatid exchanges (P = 0.001). For micronuclei, the difference (P = 0.02) between low and high exposure was statistically significant. In Mexican workers, an exposure-response relationship was observed (P = 0.002) for hemoglobin adducts but not for sister chromatid exchanges or micronuclei. PMID- 7796200 TI - Employment practices and breast cancer among radiologic technologists. AB - A case-control study of breast cancer and employment practices among female radiologic technologists was conducted. The cohort from which cases and controls were derived included over 105,000 female medical radiation workers certified by the American Registry of Radiologic Technologists during 1926-1980. Breast cancer cases (n = 528) were individually matched to an average of five control subjects (n = 2628) based on year of birth, year of certification, and length of follow up. Procedures most commonly performed by controls included fluoroscopy (93%), portable radiographs (92%), routine radiographs (92%), multifilm procedures (87%), dental x-rays (46%), radium therapy (31%), orthovoltage (23%), and cobalt 60 (21%). Breast cancer was not significantly increased with occupational experience with any of these procedures. Furthermore, risk was not related to number of years worked with a particular procedure. This study is reassuring in indicating that medical radiation workers are not at substantial risk for developing radiation-induced breast cancer. However, because only surrogate measures of radiation exposure were available, possibility of a small risk cannot be discounted. Ongoing follow-up of this cohort for incident cancers will incorporate detailed exposure assessment schemes, providing additional information on effects of long-term low-dose radiation through occupation. PMID- 7796202 TI - Occupational exposures and female breast cancer mortality in the United States. AB - Mortality records from 24 states, gathered from 1984 to 1989 and coded for occupation and industry, were used to develop leads to workplace exposures as possible breast cancer risk factors. A case-control approach was used, with separate analyses for blacks and whites. After excluding homemakers, 33,509 cases and 117,794 controls remained. A job exposure matrix was used to estimate the probability and level of 31 workplace exposures. After adjusting for socioeconomic status, suggestive associations for probability and level of exposure were found for styrene, several organic solvents (methylene chloride, carbon tetrachloride, formaldehyde), and several metals/metal oxides and acid mists. Because of the methodologic limitations of this study, its primary value is in suggesting hypotheses for further evaluation. The findings for styrene, selected solvents, and metals and metal-related exposures deserve additional study. PMID- 7796201 TI - Major differences in breast cancer risks among occupations. AB - Breast cancer incidence and mortality measured for the population of a major metropolitan center included 7368 cases and 2357 deaths over 15 years, ascertained according to National Cancer Institute Surveillance, Epidemiology, and End Results program procedures. Occupational risks were estimated with a census-based occupation coding system for cases and deaths, mean annual age standardized rates, and age-truncated occupation allocation. Data limitations include absence of population frequencies of personal risk factors for breast cancer, occupation designation errors, lack of knowledge about chemical exposures in apparently high-risk occupations, and the possibility that the number of comparisons could produce significant differences by chance. Compared to community-wide reference incidence and mortality rates, significant excess breast cancer risks were identified for housewives, registered nurses, clinical laboratory technicians, schoolteachers, social workers, secretaries and typists, and meat wrappers and cutters. High incidence rates with unremarkable mortality rates were identified for dental hygienists, religious workers, electronic engineering technicians, authors and journalists, restaurant and bar managers, realty and insurance saleswomen, bank tellers and cashiers, telephone operators, canning and bottling workers, chemical and gas handlers, and papermill workers. These findings agree in part with similar reports and will contribute to the generation of hypotheses to be tested by more specific, in-depth studies. PMID- 7796203 TI - Occupation and breast cancer risk in middle-aged women. AB - The authors analyzed data from a population-based case-control study of breast cancer in middle-aged women residing in King County, Washington, to examine the relation between occupation and breast cancer risk. A total of 537 cases and 492 controls completed in-person interviews. Subjects provided job titles and years of employment for their three main occupations since age 18. While there were case-control differences in the frequency with which certain jobs were reported, all were within the limits of chance, given no true association. Also, few additional increases in risk were associated with long-term employment. Relative risk (RR) estimates were elevated for women working in precision textile and apparel jobs (six cases and one control, RR = 5.2). To a lesser extent, RR estimates were also elevated for receptionists, cosmetologists, and the category of painters/sculptors/printmakers. A slight increase in risk was associated with several occupations, including nursing and teaching. PMID- 7796205 TI - Parity is not enough. PMID- 7796204 TI - Occupation and cervical cancer. AB - Data collected for a multicenter case-control study of invasive cervical cancer and carcinoma in situ of the cervix were analyzed with regard to occupation. Odds ratios comparing 481 invasive cases and 293 carcinoma in situ cases to 801 controls were calculated and adjusted for potential confounding factors. Working women and homemakers had a similar risk of invasive cervical cancer, with several groups of service and industrial workers showing elevated risks (particularly maids, cleaners, and cooks). Risk of carcinoma in situ was slightly increased for working women, but no occupational groups had notable associations. The principal strengths of this analysis were the ability to address both invasive cervical cancer and carcinoma in situ and to control for multiple potential confounding factors. However, occupational information was limited and risk estimates for women in specific occupations were imprecise. PMID- 7796206 TI - Predicting suicide. PMID- 7796207 TI - Treatment of bipolar depression. PMID- 7796208 TI - Evaluating changes in symptoms and functioning of dually diagnosed clients in specialized treatment. AB - OBJECTIVE: The authors outline a minimal set of outcome indicators to assess the effects of specialized treatment for people with severe mental illness and substance use disorders and report on use of these indicators in a longitudinal study of such treatments. METHODS: A total of 147 clients with dual disorders participated in a controlled clinical trial of three interventions--behavioral skills training, case management, and 12-step recovery--in a county mental health program. The clients were assessed every six months over a two-year period using multidimensional self-report and observer-rated outcome measures encompassing psychosocial functioning, psychiatric and substance abuse symptoms, and service utilization. RESULTS: Client self-reports showed changes in psychosocial functioning, especially increased functioning in residential stability and work, and reductions in alcohol and drug symptoms and usage. Data on service utilization showed decreased use of acute and subacute mental health services and increased use of outpatient and case management services over time. Ratings by trained observers of psychiatric symptoms and psychosocial functioning improved dramatically. CONCLUSIONS: A minimal set of outcome indicators for clinical trials and demonstrations of interventions for clients with dual disorders should include client self-reports of social adjustment, life satisfaction, psychiatric and substance abuse symptoms, and current substance use; interviewers' ratings of psychosocial functioning and psychiatric symptoms; data on utilization of mental health treatment and support services; and data on clients' personal income, use of medical services, and contact with the criminal justice system. PMID- 7796209 TI - A state management planning system for addressing high levels of use of inpatient psychiatric services. AB - Research on psychiatric hospital admissions shows that a small group of patients use a disproportionate amount of inpatient services. In the late 1980s Washington State developed initiatives to target outpatient community mental health services to mentally ill persons with high rates of inpatient psychiatric service use. Services to the targeted group are provided by regional support networks under contract with the state. Diverse funding sources were consolidated to give the regional authorities flexibility to tailor funding to local needs, and new appropriations were tied to the region's commitment to increase capacity for community mental health services. To support those initiatives, the state developed a specialized client-focused database to identify individuals with high rates of hospital utilization, provide information to regional authorities about use of hospital services by those individuals, and assess whether they were receiving outpatient services. Analyses of statewide data showed wide variation among regions in hospital use and delivery of community services. PMID- 7796211 TI - Long-term course of substance use disorders among patients with severe mental illness. AB - OBJECTIVE: This study assessed the long-term course of substance abuse and dependence among severely mentally ill patients. METHODS: A prospective, naturalistic, seven-year follow-up of severely mentally ill outpatients (most with schizophrenia and schizoaffective disorder) successfully located and reassessed 79.1 percent (N = 148) of the patients from the original study group. The follow-up study group was assessed for alcohol and drug use at baseline and seven-year follow-up by their case manager or primary clinician using the Case Manager Rating Scale (CMRS) for the assessment of substance-related problems among severely mentally ill patients. RESULTS: The prevalence of active substance use disorder changed little from baseline to follow-up. Alcohol abuse or dependence was present in 24 percent of the patients at baseline and 21 percent at follow-up, and drug abuse or dependence was present in 20 percent at baseline and 17 percent at follow-up. However, those with initial alcohol abuse had a higher rate of remission (67 percent) than those with initial alcohol dependence (33 percent). Similarly, those with initial drug abuse had a higher rate of remission (54 percent) than those with initial drug dependence (31 percent). CONCLUSIONS: The higher rates of change for those with initial substance abuse compared with substance dependence suggest that distinguishing between abuse and dependence may have important implications for assessment and prognosis of individuals with a dual diagnosis of a substance use disorder and severe mental illness. PMID- 7796210 TI - A collaborative approach to reduce hospitalization of developmentally disabled clients with mental illness. AB - Developmentally disabled clients with a concomitant mental illness are often underserved or inappropriately treated because of interorganizational barriers, leading to unnecessary hospitalization and lengthy delays in community placement. To overcome these barriers, agencies responsible for developmental disabilities and mental health services in Spokane County in Washington State developed a collaborative system of care in 1989. An interagency consortium was established to promote coordination of services between the community mental health center, the state hospital, the county human services agency, the state's regional developmental disability service agency, the state institution for the developmentally disabled, and several community agencies serving developmentally disabled persons. Between 1990 and 1992, admissions of developmentally disabled persons to the state hospital were more likely to be appropriate admissions of persons suffering from a mental illness, developmentally disabled clients were discharged more efficiently, and crisis respite services were used in place of hospitalization. In addition, anecdotal reports indicated a reduction of interagency tensions. PMID- 7796212 TI - A treatment-team model of managed mental health care. AB - Many models of managed care have been criticized as inflexible and intrusive, including those in which decisions about level of care are made by third-party reviewers, in-house staff, or other clinicians not involved in the patient's treatment. The treatment-team model of managed care, which has been implemented in the emergency psychiatric service of a midsized, non-profit community hospital in a metropolitan area, addresses these criticisms. Major features of the model are in-person assessment by a clinician who acts as the managed care agent; immediate accessibility of this clinician; referral services with a broad range of intensity, including crisis intervention; and participation of the managed care clinician on the treatment team. The advantages of this model include the incentive to employ qualified managed care clinicians and an increased ability to provide individualized services. Limitations of the model include the diffusion of decision-making power within the treatment team, the potential for overuse of emergency services by primary providers, and the potential for the managed care agent to lose decision-making power due to personal or systems issues. PMID- 7796213 TI - Clozapine treatment in Russia: a review of clinical research. AB - OBJECTIVE: This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States. METHODS: Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective. FINDINGS AND CONCLUSIONS: The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics. PMID- 7796214 TI - Relating functional skills of severely mentally ill clients to subjective and societal benefits. AB - OBJECTIVE: This study explored the relationship between the functional skills of clients with severe mental disorder and the benefits to the client and society as reflected by residential and vocational status, self-efficacy, self-esteem, and life satisfaction. METHODS: Relationships between various outcome variables and the demographic and clinical characteristics and staff ratings of the functional skills of 139 clients at three psychosocial rehabilitation programs for adults with severe mental disorders were analyzed using correlational techniques. The outcome variables considered were the clients' level of independence in their residential and vocational settings and their levels of self-esteem, self efficacy, and satisfaction with life. RESULTS: Ratings of functional skills correlated positively with clients' levels of residential and vocational independence and with self-efficacy, but were unrelated to self-esteem and life satisfaction. Age, education, work and hospitalization history, psychiatric diagnosis, and length of program membership were also related to these outcome measures. Skill level remained the strongest predictor of residential and vocational status after demographic and diagnostic factors were controlled for. CONCLUSIONS: Clients' functional skills have a strong, positive relationship with their level of residential and vocational independence, and skill level is a better predictor of benefits to clients and society than are demographic and diagnostic variables. PMID- 7796215 TI - Maintenance electroconvulsive therapy for chronic mentally ill patients: a case series. AB - OBJECTIVE: Maintenance electroconvulsive therapy (maintenance ECT) has emerged as an alternative treatment for patients who relapse repeatedly or cannot tolerate psychotropic medications. The pattern of maintenance ECT use in two university affiliated hospitals was surveyed to evaluate its effectiveness in treating several disorders, establish treatment guidelines, and identify adverse side effects. METHODS: Records of 161 patients who received ECT from 1976 through 1988 were reviewed retrospectively. Nine patients who received maintenance ECT- prophylactic ECT treatments administered for longer than six months--were identified. The presence of target symptoms and behaviors in the periods before and after administration of maintenance ECT was compared. RESULTS: All nine patients experienced a complete or a significant partial remission of target symptoms. Six of the nine patients were ready for transfer to less restrictive settings. Given the small number of patients, treatment guidelines could not be established; however, patients with mood disorder required less frequent treatments than patients with thought disorder. Adverse effects were documented for two of the nine patients, but they were not severe enough to discontinue treatment. CONCLUSIONS: For this sample, maintenance ECT was a safe, efficacious, and well-tolerated treatment with minimal side effects. Further, controlled studies are warranted. PMID- 7796216 TI - Characteristics and service use of long-term members of self-help agencies for mental health clients. AB - OBJECTIVE: This study examined the characteristics of long-term members of self help agencies managed and staffed by mental health clients, why they sought help from the agencies, and how they differed from clients of community mental health agencies. METHODS: A survey and assessment instruments were used to obtain information on the service utilization of 310 long-term agency members as well as on their resources, history of disability, functional status, psychological disability, health problems, and DSM-III-R diagnosis. Data from management information systems of the self-help and community mental health agencies were used to compare service populations. RESULTS: The self-help agencies served a primarily African-American population (64 percent), many of whom were homeless (46 percent). Eighty-seven percent had confirmed DSM-III-R diagnoses, and 50 percent had dual diagnoses with moderate to severe substance or alcohol abuse or dependence. They had sought help from the self-help agencies primarily for resources such as food or clothing, for "a place to be," or because they were homeless. Obtaining counseling or help for substance or alcohol abuse was a less important reason for coming to the self-help agencies. CONCLUSIONS: A high proportion of the persons served by the self-help agencies in the study were homeless and had a dual diagnosis of mental disorder and substance abuse. The self-help agencies provided their clients with material resources while community mental health agencies provided psychotherapeutic and medical care. PMID- 7796217 TI - Use of a brief behavioral skills intervention to prevent HIV infection among chronic mentally ill adults. AB - OBJECTIVE: Research shows that many chronic psychiatric patients are at risk for infection by the human immunodeficiency virus (HIV). This study investigated the effects of a behavioral skills training program designed to prevent HIV infection among chronic mentally ill adults living in an inner-city area. METHODS: Twenty seven men and 25 women were randomly assigned either to a four-session AIDS prevention program emphasizing risk education, sexual assertiveness, condom use, risk-related behavioral self-management, and problem-solving skills or to a waiting-list group, who later received the same intervention. RESULTS: Compared with the waiting-list control group, participants in the prevention program demonstrated significant gains in AIDS-related knowledge and intentions to change risk behaviors. The prevention program also significantly reduced rates of unprotected sexual intercourse and increased the use of condoms over a one-month follow-up period. A subset of participants who provided two-month follow-up data maintained some behavior changes. CONCLUSIONS: A relatively brief, skills-focused AIDS prevention program for chronic psychiatric patients produced reductions in HIV risk behaviors. Such HIV risk reduction intervention programs may be of use in inpatient, outpatient, and community-based settings. PMID- 7796218 TI - Characteristics of male and female veterans who use VA psychiatric emergency services. AB - Retrospective chart review was used to compare the demographic characteristics and psychiatric diagnoses of 150 consecutive female patients seen in psychiatric consultation in the emergency service at a Veterans Affairs medical center between 1987 and 1991 with those of two groups of 150 male patients matched by age or psychiatric diagnosis. Compared with the men, the women were younger and more likely to be divorced, to complain of anxiety or psychotic symptoms, and to have a diagnosis of a depressive disorder or borderline personality disorder. Men were more likely to have a diagnosis of schizophrenia or antisocial personality disorder. PMID- 7796219 TI - Psychiatric crisis intervention in the general emergency service of a Veterans Affairs hospital. AB - An after-hours crisis intervention program staffed by psychiatric residents between 5 p.m. and 11:30 p.m. on weekdays was developed in the general emergency room at a Veterans Affairs hospital to reduce inpatient psychiatric admissions. The program offered medication, family interventions, and referrals to outpatient services. In the programs's first year, inpatient admissions during the hours covered by the program decreased by 34 percent, for a net savings of nearly $400,000 in inpatient treatment costs. PMID- 7796220 TI - Repeat users of substance abuse services at a VA Medical Center. AB - To examine patterns of use of acute walk-in services by substance abusers, the authors studied demographic characteristics and type of substance abuse among 1,838 patients treated at a Veterans Affairs substance abuse triage unit. They found that African-American and male substance abusers appeared most likely to return for triage services. Among heroin users, the strongest predictor of return was gender. Among alcoholics, homelessness was the sole predictor of return. No predictors were found for cocaine users. The authors conclude that the relationship between return rates and type of substance abuse needs further study. PMID- 7796222 TI - The Charles Bonnet syndrome: a brief review and case report. AB - A case of a woman with visual hallucinations in the absence of other organic or psychiatric findings--symptoms consistent with a diagnosis of Charles Bonnet syndrome--is reported. The women was HIV positive, although asymptomatic for conventional complications of HIV infection. After considering possible causes of the hallucinations, including prescription drug effects and conversion or factitious disorder, the authors suggest that the woman's symptoms may have been associated with undetectable effects of HIV on the brain. PMID- 7796221 TI - Psychosocial functioning of severely disturbed adolescents after short-term hospitalization. AB - Forty-two severely emotionally disturbed adolescents discharged after a brief hospitalization for an acute psychiatric episode were assigned to two groups--one for whom clinicians recommended continued intensive treatment in an inpatient, residential, or day treatment setting, even though such services were not available, and the other for whom clinicians recommended only outpatient treatment. The two groups were compared on rates of rehospitalization, self harmful actions, and suicide attempts and on severity of problems with peers during the six months after discharge. The two groups showed significant differences only in the extent of their problems with peers. PMID- 7796224 TI - Funding health care reform. PMID- 7796223 TI - Isolated sleep paralysis. PMID- 7796225 TI - Scurvy in schizophrenia. PMID- 7796226 TI - Data from five federal demonstration projects indicate homeless mentally ill can be helped. PMID- 7796228 TI - Administration of intravenous immunoglobulins for prophylaxis or treatment of infection in preterm infants: meta-analyses. AB - AIMS: To determine the effectiveness of intravenous immunoglobulin administration to premature infants in the prevention and/or treatment of bacterial infection. METHODS: Computer searches of MEDLINE, EMBASE, SCISEARCH and Oxford Database of Perinatal Trials were made. Two independent researchers applied inclusion criteria of: randomised controlled trial; premature and/or low birthweight infant; use of intravenous immunoglobulin; and infection or mortality. Nineteen of 44 identified studies fulfilled these criteria. Study quality was assessed and information on study population, intervention, and outcomes were collected. RESULTS: Studies were divided into prophylaxis or treatment; results were tabulated for infection, sepsis, and death from all causes. For 17 studies of prophylaxis (n = 5245), the relative risk and confidence interval were, for proved infection 0.81, 0.67-0.97; for sepsis 0.87, 0.66-1.13; for death from all causes 0.85, 0.64-1.14. Some outcome results were heterogeneous. Two treatment studies showed no reduction in mortality when combined. CONCLUSIONS: Routine administration of intravenous immunoglobulin to preterm infants is not recommended. PMID- 7796227 TI - Excitatory amino acids in neonatal brain: contributions to pathology and therapeutic strategies. PMID- 7796229 TI - Longitudinal changes in the diameter of the ductus arteriosus in ventilated preterm infants: correlation with respiratory outcomes. AB - This study aimed to examine the early natural history of ductal shunting in ventilated preterm infants (< 1500 g) and to document the association between this shunting and respiratory outcomes. The size of the ductal shunt was assessed in 48 infants using serial echocardiographic measurement of colour Doppler internal ductal diameter and pulsed Doppler postductal aortic diastolic flow (PADF). At all postnatal ages, normal antegrade PADF was invariably seen when the ductal diameter was 1.5 mm or less, and was usually abnormal (absent or retrograde) when more than 1.5 mm. Longitudinal progress of ductal diameter fell into three groups: (i) asymptomatic spontaneous closure (n = 31)--in 20 of these infants closure occurred within 48 hours; (ii) symptomatic PDA which enlarged after a postnatal constriction (n = 9); and (iii) symptomatic PDA that showed minimal postnatal constriction (n = 8). Infants in group 2 were significantly less mature and had PDAs which became symptomatic significantly later than those in group 3. Logistic regression showed that ductal shunting had a significant correlation with mean oxygenation index over the first five days but not with ventilator or oxygen days. Gestation had the most significant association with the latter two variables, with atrial shunting also being related to days in oxygen. The preterm duct displays a wide spectrum of postnatal constrictive activity. Symptomatic PDAs usually showed slower early postnatal constriction. Ductal shunting independently related to short term but not long term respiratory outcomes. PMID- 7796231 TI - Fetal behaviour and the sudden infant death syndrome (SIDS). AB - To examine whether differences in sleep maturation could be identified before birth, behavioural studies were carried out in 28 fetuses. Studies were possible in all 28 fetuses at 28 weeks, but only in 26 fetuses at 36 weeks (two fetuses delivered before 36 weeks). The risk of sudden infant death syndrome (SIDS) was determined using the Oxford SIDS scoring system. The fetuses at greater risk of SIDS had coincidence of behavioural characteristics for a significantly lower percentage of the time than those at low risk. This difference reached significance (p < or = 0.05) only at 36 weeks. PMID- 7796230 TI - Blood pressure, heart rate, and skin temperature in preterm infants: associations with periventricular haemorrhage. AB - The mean arterial blood pressure (MABP), heart rate, and skin temperature were monitored every 15 minutes in the first 10 days after birth in 34 preterm infants, gestational age 24 to 33 weeks. Ultrasound brain scans carried out daily showed that a periventricular haemorrhage (PVH) occurred in a subgroup of infants (n = 15) of lower birthweight and gestational age. In infants without PVH the daily median of MABP increased with birthweight and postnatal age; that of heart rate was not affected by postnatal age, body weight, or gestational age; and that of skin temperature showed a slight fall with postnatal age. In infants with PVH, on or before the day of PVH, daily medians of MABP and skin temperature were not significantly different from those of infants without PVH, but the daily median of heart rate tended to be slightly higher. The percentage of positive correlations between the 96 15 minute values per day for heart rate and MABP increased with postnatal age and with birthweight, but did not differ in infants who developed a PVH. The coefficient of variation (CV) of the 96 15 minute values for MABP tended to be higher in infants on the day of PVH, and a similar trend was apparent on the day before. The processes of development of blood pressure, heart rate, and skin temperature are similar in infants with or without PVH but at lower gestational ages altered blood pressure control may cause brain haemorrhage. PMID- 7796232 TI - Concentrations of main serum opsonins in early infancy. AB - The evolution of the main serum opsonins in neonates and infants of varying gestational age was investigated to provide reference values for these opsonins in early infancy. Serum concentrations of immunoglobulins, IgG subclasses, C3, C4 and fibronectin were serially measured from birth until the age of 6 months in term and preterm infants. Measurements were performed by rate nephelometry. Five hundred and sixty six neonates (gestational age 26-41 weeks) were examined at birth, 233 at 1 month, 218 at 3 months, and 147 at 6 months, respectively. The same measurements were performed in 54 pairs of neonatal/maternal samples and in 230 apparently healthy adults. Gestational age had a significant impact on serum IgG, IgG subclasses, C3 and C4 up till the third month, and on fibronectin until the first month. No such impact was observed for IgA and IgM. Sixteen per cent of the neonates had IgM concentrations higher than 0.2 g/l at birth, suggesting that the critical concentration of serum IgM at birth for suspected intrauterine infection should be reconsidered. Concentrations of all opsonins at birth were significantly lower than adult reference values. They only approached or even reached adult values by the third or the sixth month. Data from analysis of the neonatal and the corresponding maternal sera indicate that there is a preferential active transplacental transport of IgG subclasses in the order of IgG1, IgG3, IgG2 and IgG4. These results show that concentrations of immunoglobulins, C3, C4 and fibronectin undergo changes during the first months of life, depending not only on the infants' postnatal age but also on gestational age. PMID- 7796233 TI - Changes in pulmonary artery pressure in infants with respiratory distress syndrome following treatment with Exosurf. AB - The pulmonary artery pressure (PAP) changes were studied using Doppler echocardiography in preterm infants treated with an artificial surfactant (Exosurf) during the acute phase of respiratory distress syndrome (RDS). The ratio of pulmonary artery acceleration time to the right ventricular ejection time (AT:RVET), measured from the Doppler wave form, was determined in 38 infants before the first dose of Exosurf, at one and six hours after the first dose, immediately before the second dose of Exosurf, and at one, six, 12, 36, and 60 hours subsequently. The median AT:RVET ratio corrected for heart rate (AT:RVET(c)) increased significantly an hour after administration of the first dose of Exosurf from 0.330 (0.273-0.410) to 0.380 (0.303-0.445) and similarly an hour after the second dose from 0.426 (0.252-0.495) to 0.440 (0.373-0.500). These changes occurred against a steady increase in the median AT:RVET(c) over the first 72 hours. It is concluded that the reduction in PAP correlates well with clinical parameters of disease severity and raises questions regarding the mode of action of Exosurf. PMID- 7796234 TI - Measurement of lung volume and optimal oxygenation during high frequency oscillation. AB - Twelve infants, median gestational age 27 weeks and postnatal age 1 day, were examined to determine whether oxygenation improves on transfer to high frequency oscillation (HFO). Lung volume was assessed before transfer to HFO by measuring functional residual capacity (FRC) using a helium gas dilution technique and specially designed infant circuit. On transfer to HFO, the inspired oxygen was initially kept constant, but the mean airway pressure (MAP) increased until maximum oxygenation was achieved (optimal MAP). The median FRC of the 12 infants before HFO was 8.1 ml/kg (range 4.7 to 28.7) and their median alveolar-arterial oxygen gradient (A-aDO2) 484 mm Hg. On transfer to HFO, oxygenation did not improve in two infants, but, overall, the A-aDO2 fell to a median of 289 mm Hg (p < 0.05). The median optimal MAP was 18.5 cm H2O (range 10.6 to 24.4) and this had an inverse correlation with the FRC before starting HFO (p < 0.01). The median change in MAP needed to maximise oxygenation on HFO also correlated negatively with FRC (p < 0.01). PMID- 7796236 TI - Synchronous intermittent mandatory ventilation modes compared with patient triggered ventilation during weaning. AB - The efficacy of combining rate and pressure reduction during weaning by synchronous intermittent mandatory ventilation (SIMV) were compared with weaning by patient triggered ventilation (PTV) (pressure reduction alone) in two randomised trials. Regardless of ventilation mode, pressure was reduced to the same level according to the size of the infant. In the first trial, the SIMV rate was also reduced progressively to a minimum of 20 breaths/minute, and in the second to five breaths/minute. Forty premature infants aged 15 days of age or less were randomly allocated into each trial. No significant differences were found in the first trial between ventilation modes in either the duration of weaning or the number of infants in whom weaning failed. In the second trial, the duration of weaning was shorter by PTV than by SIMV (median 24 hours, range 7-432 v 50 hours, range 12-500; p < 0.05); weaning failed in two infants in the PTV group and in five in the SIMV group. It is concluded that weaning by a combination of pressure and rate reduction, such as can be achieved during SIMV, offers no significant advantage over pressure reduction alone. PMID- 7796235 TI - Magnesium sulphate as an alternative and safe treatment for severe persistent pulmonary hypertension of the newborn. AB - Eleven newborns admitted consecutively to the neonatal unit with respiratory failure and severe persistent pulmonary hypertension (PPHN) were included in a clinical trial to assess the efficacy of magnesium sulphate (MgSO4) in the treatment of PPHN. A loading dose of 200 mg/kg MgSO4 was given over 20 minutes, followed by a continuous infusion of 20-150 mg/kg/hour to obtain a magnesium blood concentration between 3.5 and 5.5 mmol/l. Mean (SD) duration of treatment was 75.5 (19.8) hours. No other vasodilatory drug was administered before or during the treatment and patients were not hyperventilated. Mean (SEM) PaO2 values significantly increased from 42.6 (8.8) before treatment to 70.3 (24.1) mm Hg after 24 hours, with no change in pH or PCO2. Oxygen index and alveolar arterial oxygen gradient (A-aDO2) were significantly lower after 24 hours; respectively, 46.8 (15.2) to 28.0 (9.0) and 624.3 (11.3) to 590 (58) mm Hg. Mean airway pressure could be significantly reduced from 19.5 (3.1) to 13.9 (3.9) cm H2O after 72 hours. Mean ventilatory time support was 131 hours and mean total oxygen dependency 10 days. No systemic hypotension nor any other adverse effect were noted. All infants survived and the neurodevelopmental assessment was normal at 6 and 12 months of age. It is concluded that magnesium sulphate is a non aggressive and low-cost treatment of short duration which is easy to apply. It may have a role in the various treatment of PPHN. PMID- 7796237 TI - Application of nasal continuous positive airway pressure to early extubation in very low birthweight infants. AB - Using a preset protocol for early extubation, 50 babies were randomly selected to post-extubation headbox or post-extubation nasal continuous positive airway pressure (N-CPAP). All infants weighed less than 1500 g, had a gestational age of less than 34 weeks, and had been weaning from mechanical ventilation within seven days of life. The criteria for extubation included stable condition, fraction of inspired oxygen (FIO2) of < or = 35%, peak inspiratory pressure (PIP) of < or = 15 cm H2O (1.47 kPa), and ventilator rate of 6/minute. Before extubation, a loading dose of aminophylline was given followed by maintenance treatment. If reintubation was not required within 72 hours of the initial extubation the procedure was considered successful. The reintubation criteria included FIO2 > or = 70% to maintain arterial oxygen tension (PaO2) of > or = 50 mm Hg (6.67 kPa) or pulse oximetry between 90-96% and pH of < 7.25, and arterial carbon dioxide tension (PACO2) of > 60 mm Hg (8.00 kPa) and severe or recurring apnoea. The overall success rate of early extubation was 66% (33/50). The individual successful extubation rate of post-extubation in the N-CPAP group and the post extubation headbox group were 84% (21/25) and 48% (12/25), respectively (p = 0.017; chi 2). There were no significant differences in clinical characteristics between the two groups. The most common cause of failure in early extubation was apnoea, and most occurred in the headbox group (9/12). These results suggest that application of N-CPAP to a preset protocol for extubation can achieve a better success rate of early extubation in very low birthweight (VLBW) infants. PMID- 7796238 TI - Effect of blood transfusion on cardiorespiratory abnormalities in preterm infants. AB - The effects of red blood cell transfusion on the incidences of apnoea, bradycardia, tachycardia and oxygen desaturation over periods of 72 hours before and after transfusion were assessed in 25 infants with a gestational age of < or = 32 weeks (mean (SEM) 29.2 (0.4) weeks, birthweight 1170 (73) g; postnatal age at transfusion 39 (4) days). During transfusion haemoglobin rose from 78 (2) g/l to 117 (2) g/l. Significant decreases were observed in daily frequencies of apnoeas longer than 15 seconds (median from 2.7 to 0.9 events a day), tachycardias of more than 200 beats per minute (from 34 to 25 events per day), bradycardias below 100 beats per minute (from 65 to 12 events per day) and 80 beats per minute (from 8.4 to 3.3 events per day). Oxygen saturation improved in 20 of the infants. Transfusion improves cardiorespiration in preterm infants for several days. PMID- 7796239 TI - Absence of acidosis in the initial presentation of propionic acidaemia. AB - The clinical presentation and results of the initial biochemical and haematological investigations in 11 newborn term infants with propionic acidaemia are described. All patients had neurological symptoms. Only four had clinically important acidosis, but all had a raised blood ammonia. A diagnosis of propionic acidaemia should be considered in all newborn infants with unexplained neurological deterioration even in the absence of a metabolic acidosis. PMID- 7796240 TI - Gall bladder contractility in neonates: effects of parenteral and enteral feeding. AB - The gall bladder size was measured in 30 newborn infants: 18 had been fed parenterally and 12 enterally. The two groups were comparable for gestational age, birthweight, postnatal age and study weight. Exclusion criteria were haemodynamic instability, septicaemia, abdominal disease and opioid treatment. Gall bladder size was measured at 15 minute intervals for 90 minutes using real time ultrasonography and the volume calculated using the ellipsoid method. Parenterally fed infants had further measurements at 120, 150, and 360 minutes. The gall bladder was significantly larger in parenterally fed infants than in enterally fed infants (p = 0.0001). In enterally fed infants a 50% reduction in gall bladder volume was observed 15 minutes after starting the feed with a return to baseline volume by 90 minutes. In parenterally fed infants there was no gall bladder contraction. Such information may give insight into the pathophysiology of hepato-biliary complications during parenteral nutrition in infants. PMID- 7796241 TI - Lignocaine ointment and local anaesthesia in preterm infants. AB - The ability of topically applied lignocaine ointment to produce surface anaesthesia was examined in 45 preterm infants (gestational age 25 to 35 weeks) at a median age of 2 days. Two strengths of ointment, 5% and 30%, were tested at 30 and 60 minutes after application to the dorsum of the foot. Anaesthesia was assessed by comparing the response to skin stimulation at the test and control sites, using von Frey hairs. In 84% of cases responses indicated that there was no surface anaesthesia. Topically applied lignocaine ointment is not an effective local anaesthetic in preterm infants, presumably due to poor absorption. PMID- 7796242 TI - Aplasia cutis congenita with chromosome 12q abnormality. AB - A 32 week, small for dates baby with aplasia cutis congenita had an unbalanced translocation, being monosomic for distal 12q and trisomic for distal 1q. As far as is known, the association between extensive skin defects and a chromosomal abnormality has not been reported before. Keratin genes have been located in a different area of 12q, but this case may indicate other candidate areas to explore. Karyotyping should be undertaken in all babies with aplasia cutis. PMID- 7796243 TI - Intra-abdominal extravasation complicating parenteral nutrition in infants. AB - Two infants receiving total parenteral nutrition via a central venous catheter positioned in the inferior vena cava developed an acute abdomen secondary to extravasation of the infusate. The presence of an associated abdominal mass necessitated a laparotomy in one patient. Both infants recovered completely after the catheter had been removed. PMID- 7796244 TI - Dr William Little (1810-1894) of London and cerebral palsy. PMID- 7796245 TI - Randomised trial of early tapping in neonatal post haemorrhagic ventricular dilatation: results at 30 months. PMID- 7796246 TI - Pro- or antioxidant activity of vitamin C in preterm infants? PMID- 7796247 TI - Extensive necrotising enterocolitis after a prolonged period of supraventricular tachycardia. PMID- 7796248 TI - A longitudinal study of depression in an urban Spanish pubertal population. AB - Depression characteristics were investigated in 507 adolescents using a two-stage longitudinal study design. The three-year longitudinal study started when the girls and boys were 11 and 12 years, respectively. In the initial (screening) phase the Children's Depression Inventory (CDI) was used to select subjects for phase-II of the study in which the Children's Depression Rating Scale-Revised (CDRS-R) interview was used. The caseness definition of Major Depression (MD) and Dysthymia (D) was based on the DSM-III-R criteria. Pubertal development was assessed by Tanner's staging. Estimated prevalence of Major Depression in the female sample for each increasing year of age was 2.2%, 2.7% and 4.1%. In the male sample the prevalence for the three years was 0.9%, 0.3% and 0.6%. There was no relation to age. The estimated mean prevalence of Dysthymia was 1.4% in girls and 0.8% in boys. No association between pubertal development and depression was found. Longitudinal data support the notion of chronic depression in early adolescence. PMID- 7796249 TI - Obsessive-compulsive disorder in children and adolescents. A 6-22 year follow-up study of social outcome. AB - Twenty-eight adult males and 19 females with childhood obsessive-compulsive disorder (OCD) were followed-up in young adulthood, six to 22 years after their first referral, and their social outcome was described. The overall, social outcome was illustrated with The Global Assessment Scale (GAS). Ten patients (21.2%) had a poor outcome with GAS-scores under 50; 19 patients (40.4%) had a GAS-score between 50 and 70; and 18 (38.3%) of the patients had a good prognosis with GAS-scores over 70. Childhood OCD-patients were more socially isolated in adulthood than a non-OCD psychiatric comparison group and an age and sex standardised group from the normal population: more still lived with their parents, and fewer had partnerships. Seventeen percent had been granted disability pension, which was significantly different from the normal population, but not from that of the psychiatric comparison group. Age of onset of OCD, social background factors, and symptomatology in childhood did not seem to predict the social outcome. OCD at follow-up was strongly associated with a poor outcome. PMID- 7796251 TI - Children of a transsexual father: a successful intervention. AB - Following gender reassignment, transsexuals are often assessed in many different areas with regard to how they are functioning. However, there is little attention paid to the children they may have had prior to the operation and change in lifestyle. Children may present with problems related to the parents transsexualism, or with more generalised difficulties secondary to break-up of the family. A family of a transsexual father is described in which the children presented with difficulties and in which the intervention was successful. PMID- 7796250 TI - Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research. AB - A large number of investigation techniques are used to establish the relationships between the clinical and biological data which are necessary for physiopathological analysis in the field of developmental disorders. It therefore seemed necessary to develop a quantified grouping system, based on developmental assessments, which could allow closer matching between clinical evaluations and biological numerical data. Two hundred and two subjects presenting developmental disorders (autistic disorder, pervasive developmental disorder not otherwise specified and mental retardation) were examined. For each child, a quantification of autistic behaviour, intellectual impairment, neurological signs and language and communication disorders was performed. A cluster analysis of these quantified data elicited four subgroups according to the scores obtained in these four different areas. We showed the value of this approach by applying it to one of the studies of monoamines routinely examined in childhood autism--dopamine and HVA, its main urinary derivative. Moreover, this method revealed a subgroup within the total population which was independent of nosographic classification and which had a particular clinical and biochemical profile. Other applications could follow, for example in the fields of neurophysiology, cerebral imaging, molecular biology and genetics. PMID- 7796252 TI - Empirically based assessment and taxonomy of psychopathology: cross-cultural applications. A review. AB - This paper provides an overview of empirically based assessment and taxonomy, as illustrated by cross-cultural research on psychopathology. The empirically based approach uses standardized assessment procedures to score behavioral and emotional problems from which syndromes are derived by multivariate analyses. Items and syndromes are scored quantitatively to reflect the degree to which individuals manifest them, as reported by particular informants. Although the approach to assessing problems and to constructing taxonomic groupings differs from the ICD/DSM approach, there are no inherent contradictions between either their models for disorders nor the criterial features used to define disorders. Cross-cultural comparisons have yielded relatively small differences in problem rates and syndrome structure, plus considerable similarity in associations of problems with sex and SES, as well as similar correlations between reports by different types of informants. Research on variations in problems in relation to culture, sex, age, SES, and type of informant can contribute to improving both the ICD/DSM and empirically based approaches and to a more effective synthesis between them. PMID- 7796253 TI - Psychological adjustment of children with mild and moderately severe asthma. AB - The relationship between the severity and duration of asthma and psychological adjustment was investigated in 29 children with mild and 31 children with moderately severe asthma, who were compared with 60 healthy control children. The severity of asthma was evaluated using the Pearlman-Bierman classification. Psychological adjustment was measured using the Achenbach Child Behavior Checklist (CBCL) and a semi-structured interview. The results of the interviews indicated that regressive symptoms such as clinging, childish behaviour, dependence, and a demanding nature were widespread. Using the illness in the service of achieving other aims was also common in the asthmatic children. CBCL total problem behaviour scores, social competency, and broad band scores were significantly higher in the asthmatic group than the control sample. Problem scores for asthmatic children were significantly correlated with parental friction at home, unsatisfactory relationships with siblings and other health problems in children. However, neither the CBCL total problem scores nor the social competency scores were correlated with the severity and the duration of illness. PMID- 7796255 TI - A comparison of individual and family approaches to initial assessment. AB - The study aimed to examine the influence of initial mode of assessment on attendance, and later assessment and treatment. 100 children newly referred to a child mental health service were randomly assigned to (i) initial family assessment; child and family seen together, or (ii) individual assessment, child and parents seen in parallel. Those invited were more likely to attend following "individual" appointment letters because parents did not always bring all the children in response to "family" appointment letters. Failure to attend the second appointment occurred twice as often if there was a change in who was asked to attend. Psychometric assessment was more often requested following an initial family interview. Long term mode of therapy appeared to be partly but not wholly influenced by initial assessment method. Results suggest that sustained co operation with long term therapy is more likely to occur when clinicians vary the family members they are working with according to the needs of the case. PMID- 7796254 TI - Fears of children and the cultural context: the Turkish norms. AB - The present study was undertaken to identify children's fears in terms of their age, gender and Socio Economic Status (SES) characteristics. Another aim of the study was the adaptation and the standardization of the "Fear Survey Schedule for Children" (FSSC) to Turkish population and to determine its psychometric properties. FSSC was given to 1237 Lower SES children aged 9-13 years. To understand the effects of social and environmental factors the results were compared with 644 children from high socio-economic level and 118 children of Turkish immigrant labourer families residing in Holland. The most prevalent 10 fear items in all three groups were also determined. Results indicated that girls had more intense and frequent fears at all age levels than boys. Low SES children reveal more fears compared to their high SES pears of their self reported fears. Fears related to death and separation occupy the top positions and religious fears that are mentioned very often by children especially by those in the lower SES group. Test-retest reliability, internal consistency and the factorial structure of the scale have proved it to be a valuable and reliable tool for research and clinical purposes in Turkey. PMID- 7796256 TI - Ironing out the angles in p53. PMID- 7796257 TI - The importance of being floppy. PMID- 7796258 TI - From sticky zippers to morphology. PMID- 7796259 TI - Cystine nooses and protein specificity. PMID- 7796260 TI - Mutation of a buried residue causes loss of activity but no conformational change in the heat-labile enterotoxin of Escherichia coli. PMID- 7796261 TI - Picture story. Interacting with actin. PMID- 7796262 TI - Picture story. Pax and paired. PMID- 7796263 TI - Flexibility and function in HIV-1 protease. AB - HIV protease is a homodimeric protein whose activity is essential to viral function. We have investigated the molecular dynamics of the HIV protease, thought to be important for proteinase function, bound to high affinity inhibitors using NMR techniques. Analysis of 15N spin relaxation parameters, of all but 13 backbone amide sites, reveals the presence of significant internal motions of the protein backbone. In particular, the flaps that cover the proteins active site of the protein have terminal loops that undergo large amplitude motions on the ps to ns time scale, while the tips of the flaps undergo a conformational exchange on the microsecond time scale. This enforces the idea that the flaps of the proteinase are flexible structures that facilitate function by permitting substrate access to and product release from the active site of the enzyme. PMID- 7796265 TI - The substrate-binding site in Cu nitrite reductase and its similarity to Zn carbonic anhydrase. AB - Here we investigate the structure of the two types of copper site in nitrite reductase from Alcaligenes xylosoxidans, the molecular organisation of the enzyme when the type-2 copper is absent, and its mode of substrate binding. X-ray absorption studies provide evidence for a fourth ligand at the type-2 Cu, that substrate binds to this site and indicates that this binding does not change the type-1 Cu centre. The substrate replaces a putative water ligand and is accommodated by a lengthening of the Cu-histidine bond by approximately 0.08 A. Modelling suggests a similarity between this unusual type-2 Cu site and the Zn site in carbonic anhydrase and that nitrite is anchored by hydrogen bonds to an unligated histidine present in the type-2 Cu cavity. PMID- 7796264 TI - Bipartite structure of the alpha-lactalbumin molten globule. AB - Molten globules are thought to be general intermediates in protein folding. Apparently conflicting studies have failed to clarify whether one of the best characterized molten globules, that of alpha-lactalbumin, resembles an expanded native-like protein or a nonspecific collapsed polypeptide. Here we show that the molten globule properties of alpha-lactalbumin are largely confined to one of its two domains. The alpha-helical domain forms a helical structure with a native like tertiary fold, while the beta-sheet domain is largely unstructured. Molten globules thus possess a native-like backbone topology, but this topology does not necessarily encompass the entire polypeptide chain. Our studies indicate that molten globules provide an approximate solution to, and considerable simplification of the protein folding problem. PMID- 7796266 TI - Comparison of the free and DNA-complexed forms of the DNA-binding domain from c Myb. AB - The DNA-binding domain of c-Myb consists of three imperfect tandem repeats (R1, R2 and R3). The three repeats have similar overall architectures, each containing a helix-turn-helix variation motif. The three conserved tryptophans in each repeat participate in forming a hydrophobic core. Comparison of the three repeat structures indicated that cavities are found in the hydrophobic core of R2, which is thermally unstable. On complexation with DNA, the orientations of R2 and R3 are fixed by tight binding and their conformations are slightly changed. No significant changes occur in the chemical shifts of R1 consistent with its loose interaction with DNA. PMID- 7796267 TI - Refined solution structure of the oligomerization domain of the tumour suppressor p53. AB - The NMR solution structure of the oligomerization domain of the tumour suppressor p53 (residues 319-360) has been refined. The structure comprises a dimer of dimers, oriented in an approximately orthogonal manner. The present structure determination is based on 4,472 experimental NMR restraints which represents a three and half fold increase over our previous work in the number of NOE restraints at the tetramerization interface. A comparison with the recently solved 1.7 A resolution X-ray structure shows that the structures are very similar and that the average angular root-mean-square difference in the interhelical angles is about 1 degree. The results of recent extensive mutagenesis data and the possible effects of mutations which have been identified in human cancers are discussed in the light of the present structure. PMID- 7796269 TI - Simulating efficiently the evolution of DNA sequences. AB - Two menu-driven FORTRAN programs are described that simulate the evolution of DNA sequences in accordance with a user-specified model. This general stochastic model allows for an arbitrary stationary nucleotide composition and any transition-transversion bias during the process of base substitution. In addition, the user may define any hypothetical model tree according to which a family of sequences evolves. The programs suggest the computationally most inexpensive approach to generate nucleotide substitutions. Either reproducible or non-repeatable simulations, depending on the method of initializing the pseudo random number generator, can be performed. The corresponding options are offered by the interface menu. PMID- 7796268 TI - Flap opening in HIV-1 protease simulated by 'activated' molecular dynamics. AB - We have used an 'activated' molecular dynamics approach to simulate flap opening in HIV-1 protease. An initial impulse for flap opening was provided by applying harmonic constraints to non-flap residues. After an initial 'melting' phase, the two beta-hairpin structures that constitute the flaps opened to a 25 A gap within 200 ps of simulation. Analysis of backbone torsion angles suggests that flap opening is related to conformational changes at Lys 45, Met 46, Gly 52 and Phe 53. In contrast, similar molecular dynamics simulations on the M46I mutant, which is associated with drug resistance, indicates that this mutation stabilizes the flaps in a closed conformation. PMID- 7796270 TI - Comprehensive study on iterative algorithms of multiple sequence alignment. AB - Multiple sequence alignment is an important problem in the biosciences. To date, most multiple alignment systems have employed a tree-based algorithm, which combines the results of two-way dynamic programming in a tree-like order of sequence similarity. The alignment quality is not, however, high enough when the sequence similarity is low. Once an error occurs in the alignment process, that error can never be corrected. Recently, an effective new class of algorithms has been developed. These algorithms iteratively apply dynamic programming to partially aligned sequences to improve their alignment quality. The iteration corrects any errors that may have occurred in the alignment process. Such an iterative strategy requires heuristic search methods to solve practical alignment problems. Incorporating such methods yields various iterative algorithms. This paper reports our comprehensive comparison of iterative algorithms. We proved that performance improves remarkably when using a tree-based iterative method, which iteratively refines an alignment whenever two subalignments are merged in a tree-based way. We propose a tree-dependent, restricted partitioning technique to efficiently reduce the execution time of iterative algorithms. PMID- 7796271 TI - An investigation into the use of hypertext as a user interface to taxonomic keys. AB - In an attempt to overcome some of the drawbacks of existing taxonomic keys, we have experimented with a computerized version of a key, changing the interface to the key, but leaving the information contained in the key essentially unchanged. This is in contrast to most previous work on the use of computers in taxonomy, where work has concentrated on alternative identification techniques and techniques for manipulating taxonomic data. Hopkin's (1991) Key to the Woodlice of Britain and Ireland was converted (including the diagrams and colour photographs), into a hypertext document using the Unix Guide hypertext system. An experiment was conducted where test subjects with a wide range of experience of taxonomic keys and computing skills were asked to identify woodlouse specimens using the paper and hypertext forms of the keys. The results showed that test subjects were more likely to obtain an identification with the hypertext version of the key, they found it easier to use and preferred using it to the paper version of the key. However, there were indications that test subjects were more likely to obtain a misidentification using the hypertext key than the paper version of the key. Further work is needed to discover the possible causes of the increased frequency of misidentifications, and ways in which the usability of hypertext keys can be further enhanced. PMID- 7796272 TI - Detection of compositional constraints in nucleic acid sequences using neural networks. AB - We describe in this paper a neural network method for the detection of compositional constraints in introns and exons. The first part of the algorithm (learning phase) consisted in presenting examples of intron and exon sequences to the network and in modifying its connections using the back-propagation algorithm. Previous connectionist methods achieved the learning of exons and introns using the latter as negative examples to the former. However, we chose to learn introns and exons jointly, using junk DNA as a common counter-example. In a second part (generalization phase), we tested the neural networks in the search for exons and introns in the human globin cluster. Their performances were also checked on the classification of unknown examples. As with the previous approaches, this technique discriminates introns and exons: values of the correlation coefficients are respectively 0.50 and 0.64 for the best achieved network. Moreover, using junk DNA sequences in the learning phase allows one to detect constrained regions inside the intron and the exon sequences (i.e. sequences that differ, by their nucleic acid compositions, from junk DNA). The application of our approach could be useful in the study of the internal organization of these sequences. PMID- 7796274 TI - A rapid retrieval tool for operating on large, flat archive files. AB - Computer-aided sequencing and analysis facilities need to efficiently search flat archive files. Retrieval by e-mail or network server connections can become impractical in cases where large numbers of selected entries need to be accessed. Public versions of these archives can be retrieved via ftp and installed on a local hard disk as an alternative to network-based retrieval. After installation, a scheme is required for rapid access of the archive that is consistent with the other production needs of the sequencing facility. We have developed a retrieval system for entries inside a flat-file database. The system works for any flat file database system such as those used in the public DNA and protein archives. PMID- 7796273 TI - Implementations of BLAST for parallel computers. AB - The BLAST sequence comparison programs have been ported to a variety of parallel computers-the shared memory machine Cray Y-MP 8/864 and the distributed memory architectures Intel iPSC/860 and nCUBE. Additionally, the programs were ported to run on workstation clusters. We explain the parallelization techniques and consider the pros and cons of these methods. The BLAST programs are very well suited for parallelization for a moderate number of processors. We illustrate our results using the program blastp as an example. As input data for blastp, a 799 residue protein query sequence and the protein database PIR were used. PMID- 7796275 TI - Parameterized complexity analysis in computational biology. AB - Many computational problems in biology involve parameters for which a small range of values cover important applications. We argue that for many problems in this setting, parameterized computational complexity rather than NP-completeness is the appropriate tool for studying apparent intractability. At issue in the theory of parameterized complexity is whether a problem can be solved in time O(n alpha) for each fixed parameter value, where alpha is a constant independent of the parameter. In addition to surveying this complexity framework, we describe a new result for the Longest Common Subsequence problem. In particular, we show that the problem is hard for W[t] for all t when parameterized by the number of strings and the size of the alphabet. Lower bounds on the complexity of this basic combinatorial problem imply lower bounds on more general sequence alignment and consensus discovery problems. We also describe a number of open problems pertaining to the parameterized complexity of problems in computational biology where small parameter values are important. PMID- 7796276 TI - Finding flexible patterns in a text: an application to three-dimensional molecular matching. AB - Finding certain regularities in a text is an important problem in many areas, e.g. in the analysis of biological molecules such as nucleic acids or proteins. In the latter case, the text may be sequences of amino acids or a linear coding of three-dimensional structures, and the regularities then correspond to lexical or structural motifs common to two, or more, proteins. We first recall an earlier algorithm that found these regularities in a flexible way. Then we introduce a generalized version of this algorithm designed for the particular case of protein three-dimensional structures, since these structures present a few peculiarities that make them computationally harder to process. Finally, we give some applications of our new algorithm on concrete examples. PMID- 7796277 TI - ALIGNMENT SERVICE: creation and processing of alignments of sequences of unlimited length. AB - A package for the creation and processing of multiple sequence alignment is described. There is no limit on the lengths of the processed nucleotide or amino acid sequences, and the number of sequences in the alignment is also unlimited. The main groups of functions are: a semiautomatic alignment editor; a wide set of functions for technical processing of alignments; nucleotide alignment mapping and translation; and similarity search functions. A user-friendly interface and a set of generally used file actions provide a special operational subsystem for everyday tasks. PMID- 7796278 TI - Conformational analysis of molecular chains using nano-kinematics. AB - We present algorithms for 3-D manipulation and conformational analysis of molecular chains, when bond lengths, bond angles and related dihedral angles remain fixed. These algorithms are useful for local deformations of linear molecules, exact ring closure in cyclic molecules and molecular embedding for short chains. Other possible applications include structure prediction, protein folding, conformation energy analysis and 3D molecular matching and docking. The algorithms are applicable to all serial molecular chains and make no assumptions about their geometry. We make use of results on direct and inverse kinematics from robotics and mechanics literature and show the correspondence between kinematics and conformational analysis of molecules. In particular, we pose these problems algebraically and compute all the solutions making use of the structure of these equations and matrix computations. The algorithms have been implemented and perform well in practice. In particular, they take tens of milliseconds on current workstations for local deformations and chain closures on molecular chains consisting of six or fewer rotatable dihedral angles. PMID- 7796279 TI - An automated computer vision and robotics-based technique for 3-D flexible biomolecular docking and matching. AB - The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecular substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed. PMID- 7796280 TI - Bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. New prospects for an old warhorse. AB - The use of live M. bovis BCG to treat superficial bladder cancer has endured its seemingly anachronistic origin in the early days of tumor immunology to emerge as the therapy of choice for superficial bladder cancer. Its superiority over conventional intravesical therapy has been established for tumor prophylaxis and treatment of residual disease and CIS, providing long-term results that have translated into improvements in disease progression and survival. Although its exact mechanism of action remains elusive, extensive studies suggest that this intracellular pathogen stimulates the immune system to produce powerful cytokine mediators and effector cells that act locally to destroy bladder tumors. Although unique toxicities occur by virtue of BCG's use as a live vaccine, this same liability has opened the door for new opportunities through the use of recombinant DNA technology. Exciting prospects include the use of BCG as a cytokine carrier and as a tumor antigen depot. Genetic engineering may also yield varients that are both intrinsically safer and more specific in bladder tumor targeting. PMID- 7796281 TI - Gene therapy approaches in urologic oncology. AB - The tools and concepts of cytokine gene-based immunotherapy are being applied to the development of potentially effective new adjuvant treatment modalities for urologic malignancies. In preclinical models for the most prevalent urologic cancers, such as renal cell, bladder, and prostate carcinoma, it was shown that cytokine secreting, growth inactivated, tumor cell preparations (1) are capable of inducing a T-cell response against even nonimmunogenic tumors, (2) have considerable therapeutic benefit in tumor bearing animals, and (3) establish effective immunologic memory in cured animals. These studies have advanced further our understanding of the efficacy and therapeutic use of cytokine secreting tumor cells and form the rationale for translating these preclinical results into a clinical setting. It is realistic to speculate that in the foreseeable future alternative or complementary approaches to cytokine gene-based immunotherapy will be developed that would augment immune responses in cancer patients. Genetically modified dendritic cells transduced with genes encoding isolated tumor rejection antigens or costimulatory signals, such as B7, may be even more potent immune stimulators to induce systemic immune responses. Although animal studies have shown considerable promise and investigational clinical trials are underway, additional research and further development still is required to realize the full benefit of this approach, and some forms of cancer eventually may respond to this form of cancer immunotherapy. PMID- 7796282 TI - Renal cell carcinoma. Molecular genetics and clinical implications. AB - The combined efforts of a number of investigators have led to the identification of the VHL gene, which appears to function as a tumor suppressor gene and is implicated in both sporadic and familial forms of RCC. These findings should increase our understanding of the molecular biology of this malignancy; however, there is much work to be done. Identification of the mechanism of inactivation of the VHL gene, as well as the structure and function of the VHL gene product, ultimately may provide clinicians with greater understanding of this malignancy as well as with methods for earlier diagnosis. The role of other tumor suppressor genes, such as p53, is incompletely understood. It is hoped that the techniques that have been applied to the study of RCC also will result in advances in our knowledge of other urologic malignancies. PMID- 7796283 TI - Tumor suppressor gene alterations in bladder carcinoma. Translational correlates to clinical practice. AB - The most common tumor suppressor genes involved in the prediction of bladder tumor progression are the Rb and the p53 genes. This article summarizes current data on the use of these markers in prognostic evaluation. PMID- 7796284 TI - Genetic alterations in prostate adenocarcinoma. AB - The genetic alterations associated with prostate carcinogenesis, its progression, and the emergence of androgen independence gradually are being defined. This article focuses on a number of genetic defects that have been identified in prostate cancer, specifically as they relate to disease progression, radiation resistance, and androgen independence. PMID- 7796285 TI - The association of oncogenic human papillomaviruses with urologic malignancy. The controversies and clinical implications. AB - Sexually transmitted human papillomaviruses (HPV) are linked to both benign and malignant lesions of the genitourinary tract. Evidence links oncogenic HPV types with carcinomas of the penis and urethra. An association with other common sites of urologic malignancies (prostate, bladder) is controversial. Whereas the screening of sexually active females for HPV has received substantial attention, the presence of a potential male carrier state has received little scrutiny. Systemic immunotherapies based on expression of HPV-related proteins by infected or transformed human epithelia, however, may be possible in the near future. PMID- 7796286 TI - Continent and orthotopic urinary diversion following radical cystectomy. Should these reconstructive procedures now be considered standard of care? AB - Our extensive operative experience with various forms of the continent ileal reservoir in more than 1000 patients over the past 12 years has demonstrated clearly the extreme reliability and durability of this diversion system. Reflux reliably can be prevented and the upper urinary tracts protected. Patients can void or catheterize with confidence. Orthotopic diversions should now be available to most patients, both male and female. Patients should be able to live a more normal life style with a positive self image. We believe that because our modifications of the ileal reservoir systems have decreased the need for reoperation, these forms of continent urinary diversion have emerged as optimal operations and even as the standard of care in cystectomy patients. Ileal conduits should be reserved for poor-risk candidates with short-term life expectancy or for those patients not motivated for continent diversion. The most vocal advocates of the procedures remain those continent diversion patients who have had urinary diversion by another method. Patients still must be aware that complications can occur. Appropriate patient motivation and a thorough understanding of the continent diversion technique and its potential problems continue to be essential prerequisites of the operation. Although minor refinements to these systems will continue to be made, we feel that continent diversion, most often in the form of orthotopic reconstruction, can be offered safely and wisely most to patients. PMID- 7796287 TI - Adjuvant chemotherapy for bladder cancer. Standard of care or unproven therapy? AB - The failure of radical cystectomy to cure the majority of patients with muscle invasive transitional cell carcinoma of the bladder has prompted clinical trials evaluating adjuvant chemotherapy. No properly conducted prospective trials are available to support unequivocally the application of pre- or postsurgical chemotherapy. A large trial comparing chemotherapy with no chemotherapy and standard treatment (cystectomy) is nearing completion. The results will determine whether or not adjuvant chemotherapy becomes the standard of care. PMID- 7796290 TI - Controversies in the treatment of prostate cancer with maximal androgen deprivation. AB - The concept of maximal androgen deprivation (MAD) has become the accepted therapy for metastatic prostate cancer. MAD is also under investigation as neoadjuvant therapy prior to radical prostatectomy and radiation therapy. Innovative new approaches, such as intermittent androgen deprivation and new combination therapies, will emerge over the next decade. PMID- 7796289 TI - Laparoscopic urologic surgery. The financial realities. AB - Since 1990, laparoscopic surgery has gained an important role in the specialty of urology. This article provides a financial analysis of the three most common urolaparoscopic procedures compared with their open surgical counterpart. The intraoperative costs of laparoscopic surgery are more expensive, but the postoperative expenses are less compared with open surgery. The financial ramifications of a shorter period of convalescence following laparoscopic surgery must be considered. PMID- 7796288 TI - Conservative renal surgery. Has it a role in renal cell carcinoma? AB - Conservative renal surgery is a viable alternative for patients in whom preservation of renal function is important. The long-term survival is similar to that of radical nephrectomy, especially in low-grade malignancies. The technique is unproven in patients with a normally functioning contralateral renal unit, although it may be an option in small, peripheral, low-grade lesions. PMID- 7796291 TI - Computer modeling of prostate cancer treatment. A paradigm for oncologic management? AB - This article discusses the relevance of computer modeling to the management of prostate cancer. Several computer modeling techniques are reviewed and the advantages and disadvantages of each are discussed. An example that uses a computer model to compare alternative strategies for clinically localized prostate cancer is examined in detail. The quality of the data used in computer models is critical, and these models play an important role in medical decision making. PMID- 7796292 TI - Limited capacity for tolerization of CD4+ T cells specific for a pancreatic beta cell neo-antigen. AB - Mice transgenic for SV40 T antigen (Tag) under control of the rat insulin promoter (RIP) develop two alternative immunological phenotypes: tolerance or autoimmunity towards Tag. We utilized the T cell receptor (TCR) genes expressed in a Tag-specific CD4+ cell from an autoimmune RIP-Tag mouse to generate two lines of TCR transgenic mice in which either 10% or 90% of peripheral T cells express the transgenic TCR. When cross-bred to the tolerant RIP1-Tag2 line, mice from the low frequency TCR line showed partial deletion of peripheral Tag specific T cells and nonresponsiveness of those that remained. In contrast, crossbred mice in which transgenic T cells comprised a majority of the T cell population were nontolerant both in vivo and in vitro. Thus, tolerization of CD4+ T cells specific for a rare self-antigen may fail if too many autoreactive T cells develop. PMID- 7796293 TI - Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthritis. AB - The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated individuals and in patients with rheumatoid arthritis, an HLA-DRB1 04-associated disease. By comparing frequencies of V beta J beta combinations, healthy individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire fingerprint imposed by the HLA-DRB1 alleles involved only a selected group of J beta elements, whereas the distribution of the other J beta segments was HLA independent. The HLA-restricted J beta elements are characterized by a Gly-Pro Gly sequence within the conserved Phe-Gly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire. PMID- 7796294 TI - Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. AB - The inability of scid pro-B cells to progress to the pre-B and B cell stages is believed to be caused by a defective recombinase activity that fails to resolve chromosomal breaks resulting from attempted V(D)J recombination. In support of this model, we report that certain immunoglobulin transgenes, specifically those which strongly inhibit endogenous VH-to-DJH and V kappa-to-J kappa rearrangement in wild-type mice, allow scid pro-B cells to progress to the pre-B and B cell stages. This rescue of scid B cell differentiation is associated with a dramatic reduction in expression of the recombination activation genes, RAG1 and RAG2, and with reduced transcription of the kappa locus. PMID- 7796295 TI - In-frame TCR delta gene rearrangements play a critical role in the alpha beta/gamma delta T cell lineage decision. AB - Using a quantitative multiprobe Southern blot analysis, we demonstrate the surprising result that a significant proportion of alpha beta T cells and thymocytes retain T cell receptor delta locus sequences. A substantial portion of the retained delta locus is in a fully V-to-D-to-J rearranged configuration and 20% of these delta rearrangements are functional, significantly less than the 33% predicted for random gene rearrangements. Our observations are in conflict with the idea that alpha beta and gamma delta T cells derive from distinct precursors and suggest that commitment of a common precursor to the gamma delta lineage depends upon expression of a gamma delta T cell receptor. We propose that the intrathymic T cell lineage decision is determined by a competition between the production of functional gamma delta and beta-pre-T cell receptor complexes. PMID- 7796296 TI - Coordination of immunoglobulin chain folding and immunoglobulin chain assembly is essential for the formation of functional IgG. AB - The first constant domain (CH1) of immunoglobulin heavy (H) chains is essential for BiP-mediated retention of unassembled H chains in the endoplasmic reticulum (ER). Here, we demonstrated that both wild-type and a mutant gamma chain lacking the CH1 domain bind BiP when they are reduced in vivo. However, only oxidized mutant H chain dimers are released from BiP interaction, whereas oxidized wild type gamma chain dimers still bind BiP. In light (L) chain-producing cells, some of the mutant H chains accumulate with L chains in ER-derived vesicles and some are secreted as IgG. Furthermore, only half of the secreted antibodies bind antigen. We found the same with a mutant gamma chain, in which the CH1 domain was replaced by a CH3 domain. Therefore, we propose that BiP interaction with incompletely folded CH1 domains is required to mediate correct assembly of H and L chains. PMID- 7796297 TI - Rapid turnover of the CD3 zeta chain independent of the TCR-CD3 complex in normal T cells. AB - The function of CD3 zeta in the assembly and transport of the T cell receptor (TCR)-CD3 complex was analyzed in normal T cells. The zeta chain, but not other chains in the surface TCR complex, rapidly exchanged with newly synthesized zeta. Because zeta was expressed independently from the complex, the TCR complex may be transported to the surface along the zeta turnover pathway by association with zeta. These data suggest the dynamic nature of zeta metabolism and provide the evidence that a single component in a multisubunit receptor exhibits independent metabolism from the rest of the complex. PMID- 7796298 TI - Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. AB - Developmental-commitment to Th1 or Th2 responses critically influences host susceptibility to particular pathogens. We describe a novel mechanism governing stable commitment to Th2 differentiation. Naive T cells develop strongly polarized Th1 and Th2 profiles by 7 days after activation. However, commitment of these developing cells differs substantially. Although IL-4 reverses early Th1 differentiation, IL-12 cannot reverse early Th2 differentiation. Th1 reversibility results from maintenance of IL-4 signal transduction, whereas Th2 commitment results from rapid loss of IL-12 signaling. The IL-12 signaling defect in Th2 cells results in failure to phosphorylate Jak2, Stat3, and Stat4. Since Th2 cells express the mRNA for the cloned murine IL-12 receptor beta subunit, the signaling defect may involve expression or function of unidentified receptor components. The rapid extinction of IL-12 signaling in Th2 cells provides a demonstration of a mechanism for the stable commitment to a T helper phenotype. PMID- 7796299 TI - Stat recruitment by tyrosine-phosphorylated cytokine receptors: an ordered reversible affinity-driven process. AB - Herein, we demonstrate that purified Stat1 binds to its tyrosine-phosphorylated docking site on the IFN gamma receptor alpha chain in a direct, specific, and reversible manner. Using surface plasmon resonance, we determine the affinity (KD = 137 nM) and specificity of the interaction and define the minimum affinity needed for receptor-mediated Stat1 activation. In addition, we quantitate the relative ability of purified Stat1 to interact with tyrosine-phosphorylated binding sites on other Stat proteins. Finally, we describe experiments that imply that the unidirectional release of activated Stat1 from the IFN gamma receptor reflects the preference of free tyrosine-phosphorylated Stat1 monomers to form high avidity reciprocal homodimers rather than reassociating with the receptor binding site. Our results demonstrate that IFN gamma-induced Stat1 activation is an ordered and affinity-driven process and we propose that this process may serve as a paradigm for Stat activation by other cytokine receptors. PMID- 7796300 TI - Components of a Stat recognition code: evidence for two layers of molecular selectivity. AB - Latent and activated forms of Stat1 and Stat6 have been expressed and purified, enabling biochemical experiments relating to their functional activities. Stat1 bound to a phosphotyrosine peptide derived from the IFN gamma receptor with a KD of 50 nM, whereas Stat6 bound to an IL-4 receptor peptide with a KD of 300 nM. Stat-receptor peptide interactions were specific and dependent upon tyrosine phosphorylation. Activated forms of Stat1 and Stat6 were used to select their optimal DNA binding sites. Stat1 selected a recognition site having dyad half sites separated by 3 bp. Stat6 selected a recognition site composed of the same dyad half-sites, yet separated by 4 bp. Chimeric Stat1-Stat6 recombinants were expressed, purified, and assayed for receptor coupling and DNA binding specificity. Such studies led to the identification of polypeptide domains that specify these activities. These observations provide a framework for understanding how different cytokines elicit distinctive patterns of gene expression. PMID- 7796301 TI - Mathematical and connectionist models of human memory: a comparison. AB - Recent convolution-based models of human memory (e.g. Lewandowsky & Murdock, 1989), have accounted for a wide range of data. However such models require the relevant mathematical operations to be provided to the network. Connectionist models, in contrast, have generally addressed different data, and not all architectures are appropriate for modelling single-trial learning. Furthermore, they tend to exhibit catastrophic interference in multiple list learning. In this paper we compare the ability of convolution-based models and DARNET (Developmental Associative Recall NETwork), to account for human memory data. DARNET is a connectionist approach to human memory in which the system gradually learns to associate vectors, in one trial, into a memory trace vector. Either of the vectors can than be retrieved. It is shown that the new associative mechanism can be used to account for a wide range of relevant experimental data as successfully as can convolution-based models with the same higher-level architectures. Limitations of the models are also addressed. PMID- 7796302 TI - Learning the names of people: the role of image mediators. AB - Four experiments are reported involving the effects of bizarre and common imagery mediation techniques on the learning and 1-week retention of surnames, given videotaped faces as cues. The videotapes contained 24 undergraduates who were photographed from about the chest up, and who introduced themselves at a 20 second rate. Experiment 1 showed that for both concrete and abstract names, immediate recall of the list was better under imagery mediation instructions than under control instructions. Experiment 2 studied the same conditions using immediate recognition memory of the list as a retrieval measure for the names, and found, despite ceiling effects, that bizarre imagery instructions facilitated recognition for concrete names. Experiment 3 showed that immediate recall could be improved if subjects were given an image mediator for every face-name pair as opposed to generating their own image mediators. Experiment 4 yielded three important findings: (a) 84% of the variance in the 1-week retention of initially recalled names was explained by the presence of absence of the original mediator during 1-week recall; (b) instructions to form image mediators facilitate recall not because image mediators are more effective than other types of mediators, but because they increase the likelihood that a mediator will be formed; (c) 1-week retention could be enhanced with an increased focus during encoding on the points where the mediation process is most likely to fail. The results of these studies are discussed within the context of mediation model wherein recall can fail at any of four stages. PMID- 7796303 TI - Age differences in reported recollective experience are due to encoding effects, not response bias. AB - Three experiments examined whether reduced recollective experience reported in old age is due to a criterion shift towards more cautious responses by older subjects. In Experiment 1 Young and Old subjects took a recognition test without specific instructions on how they should encode the presented words. For recognised items subjects indicated whether they recollected the item's previous occurrence or whether they just knew it had been on the list. They then rated their confidence that the word came from the study list. Although overall recognition levels were equivalent, older adults recollected less and reported more know responses than the younger subjects. However, there was no overall difference in confidence, contrary to a criterion shift explanation. In Experiment 2A specific encoding instructions removed the age-related change in recollective experience entirely. Experiment 2B reproduced the test conditions of Experiment 2A, but without specific encoding instructions, and replicated the pattern of know responding found in Experiment 1. Thus the three experiments together suggest that the amount of recollection experienced by the elderly is not explicable in terms of cautiousness, but is driven by the encoding carried out by the elderly at presentation. PMID- 7796304 TI - The constituent structure of subjective memory questionnaires: evidence from multiple sclerosis. AB - A number of different instruments have been devised for investigating individual differences in memory on the basis of subjective reports. One such questionnaire was mailed to individuals on a register of patients with multiple sclerosis, a condition that is known to be associated with objective impairments in cognition and memory. A similar questionnaire was enclosed to be completed about each patient by a close relative. The patients' and relatives' responses were found to share a factor structure identifying memory problems in five areas: receptive communication, route finding, absent-mindedness, face recognition, and expressive communication. These were dominated by a single second-order factor representing a global subjective memory impairment. There were some minor differences between the patients and relatives in their factor scores, but there was generally a high degree of concordance in their responses. PMID- 7796305 TI - Functions of external cues in prospective memory. AB - A simulation of an air traffic control task was the setting for an investigation of the functions of external cues in prospective memory. External cues can support the triggering of an action or memory for the content of the action. We focused on memory for the content, and manipulated the temporal characteristics of the external cue to disentangle two possible functions the cue can support: (1) an external cue visible during a retention interval could support rehearsal of the to-be-performed action; (2) an external cue visible at the end of a retention interval could support retrieval of the to-be-performed action. Two experiments were conducted that converge on the same conclusion: the primary function of an external cue is to support retrieval. Implications for the design of a computer interface to present prospective cues are discussed. PMID- 7796306 TI - No-observed-effect level of diborane on the respiratory organs of male mice in acute and subacute inhalation experiments. AB - In order to clarify the acute and subacute toxicity of diborane (B2H6, CAS: 19287 45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.02 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe. PMID- 7796308 TI - The relationship between job status, gender and work-related stress amongst middle-aged employees in a computer manufacturing company. PMID- 7796307 TI - The relationship between being satisfied with one's health, good health practices and personal symptoms of ill health. AB - The focus of this study was satisfaction with health and its relationship to good health practices, symptoms and current use of medication. A self-administered questionnaire was circulated to employees of a railroad company. 3,639 males aged 18 to 54 (41.4 +/- 7.61) were selected. Seven good health practices each scored 1 were not smoking including quitting, not drinking or drinking less than six days a week, exercise more than two days per week, body mass index (BMI) being 20 to 28, total nightly sleeping time between six and nine hours, having breakfast everyday, and not eating between meals. Each score was summed up as health practice index (HPI). We also asked about health satisfaction for the past year, subjective symptoms over the last two to three months, and present medication history. HPI increased significantly in the group aged 45 to 54, this group being satisfied with their health. A decrease in the percentage of eating between meals in the under 35 group, inappropriate BMI in the 45 to 54 group, and regular exercise in the group aged 50 or older was recognized. Health satisfaction was predicted using symptoms, present medication, age and health practice. Standardized discriminant coefficients of symptoms and present medication were 0.672 and 0.610, and they were more associated to health satisfaction than health practice. PMID- 7796309 TI - [Studies on factors influencing the attack of subarachnoid hemorrhage during labor]. AB - We analyzed factors affecting attacks of subarachnoid hemorrhage (SAH) retrospectively in 411 patients and studied the relation of the attacks with labor. The onset time of SAH has two peaks of the time: one is 7:00 a.m. and the other is between 16:00 and 17:00 in the afternoon. The attacks of SAH during labor were observed in 15.1% of all the patients. It was noted that 66.7% of all the attacks were observed at the time with certain external stress such as working, sporting, sexual intercourse, etc. The number of patients who suffered from attacks during labor with history of hypertension and insomnia were not significantly different compared with those suffered from attacks during other activities, but 40-59 aged men those who have a history of smoking were significantly more in number compared with those that suffered attacks during other activities. Transient increase of blood pressure due to external stress is suggested as an initiative factor of the bleeding during working. Reactivity of the individuals against physical and mental stress (external stress) might be considered to be the major problem, although it remains not to be unexplained whether labor itself participates in the onset of SAH. Regarding the prevention of SAH during labor, new methods of medical examination and health control is required. PMID- 7796310 TI - [A study for the practical use of the mask fitting tester]. AB - The standards require replaceable dust respirators to be designed so that the wearer can easily check facepiece-to-face fitting at any time. The common practice adopted is an air leakage examination between the facepiece and the face in a negative pressure created by sealling-off inhalation area and breathing-in (called "a negative pressure method"). This method offers only subjective testing made by the wearer himself or herself, no objective testing is possible by the third party including supervisors and hygiene staff. Accordingly, we conducted the practical use test of the Mask Fitting Tester (Model MT-02, Roken type) by letting wearers to use the tester at a sanitaryware plant where workers are well instructed for how to wear respirators and also respirators are used in good care and maintenance. In addition, a questionnaire survey was conducted to investigate how wearers perceive the practical use of the Mask Tester. The following are the conclusions of the study and the survey for the practical use of the Mask Tester. 1) At the first fitness test, when examinees wear the respirator as in the usual manner without given particular instructions, 50% of examinees are found unachieved with the leakage rate of the desired value of 5% of less. 2) All the examinees unachieved were instructed by hygiene staff followed by fitting test to check their leakage rate until they pass the desired value. After repeating this three times, there were no examinees found unachieved. 3) 88.2% of these examinees could achieve the desired value only by adjusting headbands and correcting the position of facepiece under instructions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796312 TI - [Effects of physical exercise on the mercuric chloride-induced acute renal failure in mice]. PMID- 7796313 TI - [Study on quantitative analysis of free silica content in sample dust made by established specific gravity]. PMID- 7796314 TI - [A survey of the inclinations of medical students towards becoming occupational physicians]. AB - We conducted a survey to investigate medical students awareness of the activities of occupational physicians and their willingness to do postgraduate courses in this field. Those surveyed were fifth grade students in six universities in the Kinki district of Japan in 1993. In analyzing the responses of 368 eligible subjects, the response rate was 68.4% and the following results were obtained. 1) Only one of the 368 subjects expressed a desire to become an occupational physician after graduation, however 24.2% of those surveyed had considered becoming occupational physicians. More female students and, males over the age of 25, had considered becoming occupational physicians. Anxiety about a possible surplus of medical doctors in the near future was a factor that led them to consider becoming occupational physicians. 2) There were few negative responses concerning the activities of occupational physicians, even among those who had not considered becoming occupational physicians. 88.3% of those surveyed complained of a lack of information regarding postgraduate courses. 3) Responses were varied concerning conditions in the practice of occupational physicians. Those who had considered becoming occupational physicians were mostly concerned with the establishment of a system for the acceptance of occupational physicians in industry, while those who had not thought of becoming occupational physicians, considered practicing as occupational physicians as a sideline to regular clinic duties. 4) Having considered the above results and those of other researchers, we concluded that supplying more information related to the activities of occupational physicians and offering further postgraduate training programs in occupational medicine would encourage more medical students to become occupational physicians. PMID- 7796311 TI - [7 years of annual mass screening for colorectal cancer in office workers- usefulness of 3-day RPHA method]. AB - Immunological fecal occult blood test have been proved to be useful in the mass screening for colorectal cancer. Since 1986, we have started annual mass screening by the use of 3-day RPHA method and medical questionnaire for office workers over 40 yr old. During 7 yr, 261 out of 5386 examinees were testing positive for fecal occult blood, a test positive rate was 4.8% and 12 colorectal cancer (7: early, 5: advanced) were found. Among 12 cases, 10 were detected by positive results of RPHA test and 2 by questionnaires of symptoms or family history. The sensitivity and specificity of this method were calculated at 83.3% and 95.3% respectively. But as for advanced cancers, the sensitivity of this method was 100%. 75% of patients with colorectal cancer were over 55 yr old. The predictive value of positive test (PV) were much more higher in subjects with 2 or 3 times test positive (high risk group: PV = 14.3%) than in subject with only 1 time test positive (low risk group: PV = 0.6%). So it is considered to be reasonable that the high risk group (24% of total test positive) should be immediately undergone further examinations (Ba. enema or colonoscopy), and the low risk group should be undergone re-examinations of 3-day RPHA method. By this system, almost 50% of further examinations will be reduced. In conclusion, 3-day RPHA method with this further examination system is reasonable and efficient for screening of colorectal cancer in office workers, considering the high reliability in cancer detection and decreased further examinations. PMID- 7796315 TI - [Experimental techniques for developing new drugs acting on dementia (9)--Brain ischemia models]. AB - Many brain ischemia models have so far been developed and used for investigating the pathophysiology of ischemic stroke. Among these stroke models, gerbil models of brain ischemia have been widely used because of several advantages such as easy operability and convenience. In the present paper, we first discuss several subjects related to the use of animal models of brain ischemia for the development of new therapeutic agents against vascular dementia, and the theoretical, technical and clinical implications of gerbil models of brain ischemia have been outlined. Secondly, we describe the detailed procedures for obtaining forebrain ischemia or four different grades of unilateral cerebral ischemia in Mongolian gerbils. The advantages and drawbacks of these models are also discussed and compared with other models for investigation of the pathophysiology of vascular dementia. PMID- 7796316 TI - [Assessment of anxiolytics (1)--Geller-type conflict tests]. AB - The Geller-type conflict test and its modified tests, which are based on operant conditioning, have been applied for preclinical evaluation of the anxiolytic effect of drugs in parallel with the clinical use of benzodiazepines. Here, the author describes the experimental procedures of the Geller-type conflict test, including its modified tests, using mice and rats in detail. The effects of drugs, particularly benzodiazepines and 5-HT1A receptor agonists, on the established conflict behaviors in rats and mice are also presented. PMID- 7796317 TI - [Assessment of anxiolytics (2)--An elevated plus-maze test]. AB - When rodents are placed on an elevated plus-maze which consisted of two enclosed arms and two open arms, they enter the enclosed arms more frequently and spend more time on the enclosed arms than on the open arms since they prefer the enclosed arms to the open arms. The elevated plus-maze test can measure effects of drugs based on this tendency of rodents. Anxiolytics increase the time spent on the open arms and number of entries into open arms, and anxiogenics decrease them. We investigated the basal behavior of mice and the effects of diazepam in the elevated plus-maze test using 4 mazes with different size. The basal behavior of mice were changed by the maze size, especially by the width of the open arms. Further, we suggested that the maze size might affect anxiolytic activity of drugs detected in this test. This test is very useful because it needs neither complicated training for rodents nor an expensive apparatus, and the anxiolytic effects of drugs can be easily measured. However, this test is difficult to detect putative anxiolytics acting on serotonin receptors. When this method is used for measuring the activity of drugs, the choice of experimental conditions and evaluation of the results should be carefully done. PMID- 7796318 TI - [Effect of monoamines and antidepressant drugs on calcium-dependent current generating the afterhyperpolarization of hippocampal pyramidal cells]. AB - A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to investigate the membrane current responsible for the slow afterhyperpolarization (AHP) in CA3 pyramidal cells and the effects of monoamines and antidepressant drugs on this current were studied. This was achieved by using conventional procedure to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid voltage clamp). The current generating the AHP (IAHP) could be blocked by cadmium- or Ca(2+)-free medium and showed a requirement for voltage-dependent Ca2+ entry. Noradrenaline and serotonin, 10 microMs in bathing medium, respectively, reduced the IAHP evoked by short duration depolarizing current. Pharmacologically different antidepressants such as maprotiline or fluvoxamine, 10 microM in bathing medium also reduce the IAHP. Chlorpromazine and haloperidol which have no antidepressant effect had no effect on IAHP. These results suggest that the enhancement of neuronal excitability which reflect the blocking of Ca(2+)-dependent potassium conductance may be the common mechanism of action of pharmacologically different antidepressant drugs. PMID- 7796320 TI - Prevention by minaprine of ischemic neuronal damage and memory impairment in Mongolian gerbils. AB - This study examines the effect of the psychotropic drug minaprine on memory impairment in Mongolian gerbils subjected to a 5-min bilateral common carotid artery occlusion, as assessed by their performance in an 8-arm radial maze task. Gerbils were initially trained on the 8-arm radial maze until their mean error was 0-1 for 5 days. This task was repeated before the ischemia was performed and again 7 days after it. Then the animals were immediately sacrificed for histopathological examination. Severe memory impairment occurred in the control gerbils; whereas when minaprine 75 mg/kg was given orally 30 min before the 5-min occlusion, memory impairment was significantly reduced. Histopathological analysis of the control gerbils showed nearly complete loss of the pyramidal neurons in the CA1 region of the hippocampus, whereas the minaprine-treated gerbils showed complete preservation of the pyramidal neurons. These findings suggest that minaprine has memory-impairment-prevention and neuroprotective effects against short-term ischemia in gerbils. PMID- 7796322 TI - [Proteoglycans in the developing brain]. AB - The occurrence of multiple proteoglycan species is a characteristic of the brain. To identify each proteoglycan molecule, we have raised several monoclonal antibodies against either the soluble or membrane-bound proteoglycan fraction from 10-day-old rat brains. The monoclonal antibody 1G2 recognized neurocan, a soluble chondroitin sulfate proteoglycan (CSPG) unique to the brain. Immunohistological and cell biological results suggested that neurocan regulates neurite outgrowth through specific binding to N-CAM and Ng-CAM at the surface of neurons. In addition, the expression of neurocan was dependent upon neuronal activity evoked by environmental stimuli at least in the developing barrel field. Another CSPG, 6B4-PG, was expressed specifically in the cerebellar mossy fiber system in the rat hindbrain, suggesting that it plays roles in the establishment of this particular neuronal circuit. A membrane-bound heparan sulfate proteoglycan with a 140 kDa core glycoprotein (tentatively designated growth-can) was shown immunohistologically to be transiently expressed in association with growing axons and at the sites of synapse formation. Thus, many neuronal proteoglycans may be involved in various phases of neuronal network formation in the brain. In the near future, progress both in molecular cloning of core proteins and in glycobiology of carbohydrates of proteoglycans will probably produce much experimental evidence to show that neural proteoglycans play pivotal roles during various stages of brain development. PMID- 7796321 TI - Effect of diabetes on the morphine-induced inhibition of gastrointestinal transit. AB - The effect of diabetes on the morphine-induced inhibition of gastrointestinal transit was examined in mice. Morphine dose-dependently inhibited gastrointestinal transit after s.c. administration in both non-diabetic mice and diabetic mice. There was no significant difference between the ED50 values for this antitransit effect of morphine in non-diabetic and diabetic mice. The gastrointestinal antitransit effect of morphine was significantly antagonized by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.), a selective mu-opioid receptor antagonist, in both non-diabetic and diabetic mice. However, pretreatment with naloxonazine (35 mg/kg, s.c.), a selective mu 1-opioid receptor antagonist, had no effect on the antitransit properties of morphine. These results suggest that diabetes failed to alter the mu 2-opioid receptor-mediated antitransit effect of morphine. PMID- 7796319 TI - [In vivo neurochemical effects of electroconvulsive shock on the forced swimming rat]. AB - The effects of electroconvulsive shock (ECS) on monoamine metabolism in the forced swimming rat were studied using on-line microdialysis. In the present experiment, we measured forced swimming-induced immobility time and interstitial concentrations of dopamine (DA), its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and serotonin (5-HT), its metabolite 5 hydroxyindoleacetic acid (5-HIAA) in the anterior hypothalamus. Mean immobility time was short in the ECS-treated group compared with shamECS group but the difference was not statistically significant. DA and 5-HT tended to increase following a single ECS. Interstitial concentration of 5-HIAA increased significantly. Forced swimming test caused an increase in both DA and 5-HT turnover in the hypothalamus. In contrast, pretreatment with ECS tends to suppress these forced swimming-induced increases in DA and 5-HT turnover. These data suggest that ECS may regulate excess activation in central dopaminergic and serotonergic system following forced swimming stress. PMID- 7796323 TI - [Discovery of HTLV-I associated myelopathy]. PMID- 7796324 TI - [Recent progress in development of psychotropic drugs (1)--Anti-anxiety drugs]. AB - Anti-anxiety drugs are widely used for patients with neurosis or psychosomatic diseases due to the stress of contemporary society. The high efficacy of benzodiazepine (BZD) or its analog, which contains diazepam, is well-known. While these compounds have strong anti-anxiety effects, it has recently been pointed out that they have some side effects when used as daytime tranquilizers and induce drug dependence. The cause of these side effects is thought to be that typical BZD is a full agonist of BZD receptors. For this reason, partial agonists, inverse agonists and antagonists of BZD receptors are being developed. Furthermore, some non-BZD anti-anxiety drugs are also being developed to avoid the side effects of BZD. One of these is a 5-HT1A agonist, which has a high affinity for 5-HT receptors, because it is reported that 5-HT is related to anxiety in the septum-hippocampus system. In addition, the anti-anxiety effect of 5-HT3 agonist is being investigated, while the anti-anxiety effect of cholecystokinin agonists is also attracting attention. Because these new anti anxiety drugs are more potent and have fewer side effects than BZD, they may achieve widespread clinical use. PMID- 7796325 TI - [Possible roles of brain histamine H3 receptors and the pharmacology of its ligands]. AB - The discovery of the presynaptic histamine H3 receptors confirmed the idea that histamine is a neurotransmitter in the mammalian brain. The H3 receptors (autoreceptors) regulate the release and synthesis of histamine. The H3 receptors also modulate the other neurotransmitters (heteroreceptors). Subclasses of H3 antagonist binding sites were found in the brain (H3A and H3B). The regulation of noradrenaline release is reported to be mediated by H3A rather than H3B. The H3 binding site belongs to the class of receptors coupled to G-proteins. Besides the molecular data, this review focuses on the functional roles of H3 receptors in the brain and discusses the possible use of H3 ligands for neurobehavioral disorders. The pharmacological data of H3 ligands may provide clinical candidates for CNS disorders in which histamine plays important roles in mental and behavioral functions. Especially, H3 antagonists may be useful for CNS disorders such as narcolepsy, dementia, epilepsy, and obesity, while H3 agonists may provide for anxiety, insomnia, migraine. However, these suggestions are still preliminary and further clinical research is needed, although potent and safe novel H3 ligands are being developed. PMID- 7796327 TI - Surgical techniques for preparation of teaser bulls. AB - Each method of surgical preparation of teaser bulls has distinctive advantages and disadvantages. The selection of a method is influenced by the veterinarian, the owner, and the circumstances involved. The goal of surgery is safe, effective, and economical production of teaser bulls. PMID- 7796326 TI - Teat and udder surgery. AB - Teat and udder surgery is certainly one of the major areas of soft tissue surgery. In recent years, there have been great advances in what can be accomplished with teat and udder surgery. This article reviews teat and udder surgery from the simplest technique to the most complex. Diagnosis and prognosis are covered, as well as the actual surgical techniques. PMID- 7796329 TI - Ocular surgery. AB - The techniques described are considered field techniques. Adequate restraint and the ability to perform the blocking techniques are critical. Selection of a technique should be based on severity of the lesion, type of lesion, function of the animal, and economics. Application of less radical techniques should be preformed when possible; alternatives to enucleation exist in many cases. PMID- 7796330 TI - Surgical (cosmetic) dehorning in cattle. AB - Numerous methods have been developed through the ages to dehorn cattle. Some are clever and sophisticated; others are crude. Most methods can be used effectively and humanely, and with desirable cosmetic results. This article discusses the cosmetic and ethical considerations for dehorning, as well as surgical preparation and techniques used. PMID- 7796328 TI - Umbilical hernias, umbilical abscesses, and urachal fistulas. Surgical considerations. AB - Swellings of the umbilical stalk, with or without herniation, are common findings in calves. Differentiation of involved structures is helpful in deciding the surgical approach and type of anesthesia required. This article deals with clinical signs, diagnostic procedures, and surgical techniques used to repair problems related to the umbilical stalk. PMID- 7796333 TI - Dehorning the adult goat. AB - Although goats are ideally disbudded as infants, occasionally they are not. Goats grow horns much more rapidly than most owners realize and use these horns on other goats and, occasionally, people. Dehorning adult goats is not as easy as dehorning cattle. The techniques for tranquilizing, anesthetizing, and dehorning adult goats is described and aftercare is discussed. PMID- 7796331 TI - Tracheal collapse. AB - Tracheal collapse in calves usually is associated with dystocia at birth, especially breech presentations. Inspiratory dyspnea typically is seen within the first several months of life and may worsen progressively. Lateral cervical radiographs are useful in defining the affected segments as well as identifying previously fractured ribs. Surgical stenting of the trachea will improve the calf's condition, but because this procedure is done on young calves, the tracheal diameter of the affected segment is permanently limited by the size of the prosthesis. PMID- 7796332 TI - Surgical treatment of pleuritis and pericarditis. AB - Surgery of the bovine chest is rarely attempted; however, there are distinct indications and procedures available to treat both pericarditis, suppurative pleuritis and pleural effusions. Open lavage of the pericardial sac or pleural space has proven successful in carefully selected cases. The surgical procedures for pericardiotomy and thoracotomy are discussed. PMID- 7796337 TI - Urinary surgery. AB - This article describes diagnosis, prognosis, pathophysiology, and methods to surgically correct abnormalities of the urinary system of ruminants. Surgery of the urinary system in ruminants most frequently is required to alleviate urethral obstruction or correct urinary bladder rupture. Several options for surgical management of those conditions are presented, but the prognosis for long-term survival or a return to reproductive function is poor if a urethrostomy is performed. Nephrectomy, translocation of ectopic ureters, removal of urachal remnants, and urethral extension to treat urovagina are performed less often in ruminants because animals requiring these procedures often are culled because of economic considerations or decreased productivity. Consequently, much of what has been described for ruminants is based on a limited number of cases or extrapolated from what has been learned from other species. PMID- 7796335 TI - Female reproductive surgery. AB - Although cesarean section is covered in a separate article, this article on miscellaneous female reproductive surgery will hopefully help to get and keep the cow pregnant. Procedure such as rectovaginal lacerations, vaginal tumors, prolapsed cervical rings, and vaginal prolapse repair are covered. In addition to procedures that will help with pregnancy, ovariectomy and hysterectomy are also covered. PMID- 7796334 TI - Cesarean section. AB - Cesarean section has become a common surgical procedure and there is a tendency for both veterinarians and their clients to regard it as routine. It is important to remember, however, that a cesarean section entails major abdominal surgery, with inherent risks, irrespective of the prevailing conditions or personnel involved. PMID- 7796336 TI - Male reproductive surgery. AB - Copulation failure in food animals can be economically devastating to producers. Many pathological conditions can result in the inability of an animal to breed. In this article, diagnosis, pathophysiology, and treatment of penile and preputial injuries and anomalies, and inguinal hernias are presented. Surgical procedures are described for castration, seminal vesiculitis, circumcision, preputial diverticulectomy, penile hematoma, inguinal herniorrhaphy, phallorrhaphy, correction of filling defects of the corpus cavernosum, fibropapilloma, persistent penile frenulum, penile hair ring, and urethral fistulae. PMID- 7796339 TI - Demonstration that bone mineral density of the lumbar spine, trochanter, and femoral neck is higher in black than in white young men. AB - The incidence of osteoporosis and fractures of the hip and spine is lower in black than in white subjects. To determine whether bone mass is increased in black men and to assess the influence of body weight and age, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry in 59 normal white men and 40 black men between the ages of 20 and 50 years. Body weight and age were not different from each other in the two groups. BMD of the midradius was measured by single-photon absorptiometry. Multivariate regression was used for independent analysis of each group and for analysis of the two groups together. After adjusting for body weight, age was inversely related to BMD of the femoral neck in both blacks and whites and of the trochanter in blacks. When body weight was analyzed independently of age, it was a positive predictor for BMD of the midradius of black men and of the femoral neck in white men. Despite the racial differences in age and weight on BMD, there were no significant interactions between race and age or race and weight when the data from black and white men were combined. Race had a highly significant effect on BMD of the lumbar spine, trochanter, and femoral neck midradius, and BMD was higher in blacks than in whites at these sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796338 TI - Perspectives: on a "paradigm shift" developing in skeletal science. PMID- 7796340 TI - Dual-energy X-ray absorptiometry of the calcaneus: comparison with vertebral dual energy X-ray absorptiometry and quantitative computed tomography. AB - The purpose of this study was to determine the efficacy of using bone mineral measurements of the calcaneus to evaluate osteoporosis. Dual energy X-ray absorptiometry (DXA) of the calcaneus was compared with posteroanterior lumbar absorptiometry (DXA) and vertebral quantitative computed tomography (QCT) measurements in 171 white women (78 normal and 93 osteoporotic). DXA measurement of os calcis mineralization decreased significantly in osteoporosis, but to a lesser extent than in vertebral sites. In normal subjects, good correlations were observed between calcaneal and lumbar DXA (0.69) and QCT (0.56). In subjects with vertebral fractures, there was also good correlation between calcaneal DXA and QCT (0.59-0.69). This suggests that trabecular bone in calcaneus and vertebrae have related involution in cases of vertebral osteoporosis. However, the extent of bone loss is less marked in the calcaneus than in the vertebrae and is not sufficient to be accurately measured over time. We conclude, therefore, that although the global densitometric measurement at this site is not sufficiently sensitive for general use, it can be useful as a epidemiological research tool. PMID- 7796342 TI - Bilateral comparison of femoral bone density and hip axis length from single and fan beam DXA scans. AB - Dominant/nondominant differences in bone mineral density (BMD) have been observed in the upper extremities. However for the proximal femur, the distinction between dominant and nondominant hips is not clear. The purpose of this study is to evaluate left/right variations in femoral BMD and hip axis length (HAL) in both single beam and fan beam dual x-ray absorptiometry (DXA) scans. A total of 36 women aged 41-76 years (average age 60 +/- 10 years) received single beam and fan beam DXA scans of both proximal femora with a Hologic QDR-2000 scanner. Femoral BMD and hip axis length were determined for each scan. Left/right and single beam/fan beam correlations were determined and differences were evaluated using a two-way analysis of variance. Femoral BMD at corresponding measurement regions in opposing femora were highly correlated (r = 0.81-0.96). No significant left/right differences were detected. At the femoral neck, the mean BMD difference (+/- standard deviation) was 1.5% +/- 4.7% in a single beam mode and -0.6% +/- 6.3% in fan beam mode. Though mean values of femoral BMD were equivalent, the observed individual left/right differences were occasionally large (as high as 26% in the femoral neck). The hip axis length of the left and right hips were highly correlated and statistically equivalent. However, hip axis length using fan beam was significantly larger (7.5%) than the single beam measurement with a larger observed variation. We conclude that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796341 TI - Factors influencing short-term precision of dual X-ray bone absorptiometry (DXA) of spine and femur. AB - In this study we analyzed the effect of variations in bone area size, baseline soft tissue composition represented by the R-value, and bone region of interest positioning on the precision in vivo of bone mineral density (BMD) and content (BMC) as measured by dual X-ray absorptiometry (DXA). The posterior-anterior (PA) spine, decubitus lateral, and femur modes were evaluated. Eleven (PA-spine), 9 (dec-lat), and 14 (femur) postmenopausal women were scanned twice on a Norland XR 26 with repositioning to determine short-term precision of BMD, BMC, AREA, and the R-value. Phantom precisions (CV[%] of 10 consecutive scans) for BMD (BMC) were PA spine: 0.66% (0.57%), neck: 1.1% (1.2%), and trochanter: 0.55% (1.0%). Precisions in vivo (CV[%]; two consecutive scans averaged over all patients) were PA spine: 0.9% (1.0%), dec-lat: 7.1% (18%), neck: 1.3% (1.9%), and trochanter: 2.5% (4.9%). BMD precision could be fully explained by BMC and AREA variations. However, BMC alone was a particularly poor predictor of BMD in the dec-lat (r2 = 0.05) and in the neck (r2 = 0.13) modes. AREA was a strong predictor for BMC precision explaining between 41% and 88% of the BMC changes. Changes in soft tissue composition contributed significantly in explaining the BMC changes in the dec-lat projection. A higher dependence of BMC changes on AREA changes resulted in a larger difference between BMC and BMD precision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796343 TI - Serum calcitonin forms and concentrations in young and elderly healthy females. AB - To further investigate the role of calcitonin (CT) in normal physiology we studied circulating forms and the secretion after "calcium clamp" in young and elderly healthy females. Heterogeneity of CT in serum was disclosed after immunoextraction, fast protein liquid chromatography, and radioimmunoassay in young (27 +/- 3 years; mean +/- SD, n = 6) and elderly females (69 +/- 6 years, n = 11). Three distinct molecular forms appeared with approximate mol wt of 30, 10, and 3-4 kDa. All young women studied had considerable amounts of circulating monomer-like CT whereas several elderly had undetectable or low levels. The influence of age on basal and calcium stimulated, immunoextracted CT in serum was also studied in young (26 +/- 4 years; mean +/- SD, n = 13) and elderly (63 +/- 6 years; n = 12) healthy females. The calcium stimulation was carried out by means of the standardized calcium clamp method, where calcium was kept on a presettled level at 1.45 mmol/liter (+/- 2%) for 60 minutes. CT was immunoextracted from serum in all series of experiments with a polyclonal antiserum directed against the mid- and carboxyterminal region of the CT molecule, and the amount of extracted CT was determined by radioimmunoassay using another polyclonal antiserum against the carboxyterminal portion. After calcium infusion, the increase in CT was significantly higher in young women than in elderly (P < 0.05). At basal conditions, the CT levels were not significantly different but slightly higher in young than in elderly females. In conclusion, several elderly women lack monomer-like calcitonin in serum in contrast to young women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796344 TI - Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: the role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment. AB - Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42-56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P < 0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonin-treated patients showed a significant increase in bone mineral content of spine and proximal forearm (P < 0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796345 TI - Low dose phenytoin is an osteogenic agent in the rat. AB - Long-term use of phenytoin for the treatment of epilepsy has been associated with increased thickness of craniofacial bones. The aim of the present study was to evaluate the possibility that low doses of phenytoin are osteogenic in vivo by measuring the effects of phenytoin administration on serum and bone histomorphometric parameters of bone formation in two rat experiments. In the first experiment, four groups of adult male Sprague-Dawley rats received daily I.P. injections of 0, 5, 50, or 150 mg/kg/day of phenytoin, respectively, for 47 days. Serum alkaline phosphatase (ALP) and osteocalcin were increased by 5 and 50 mg/kg/day phenytoin. The increases in osteocalcin and ALP occurred by day 7 and day 21, respectively. The tibial diaphyseal mineral apposition rate (MAR) at sacrifice (day 48) was significantly increased in rats receiving 5 mg/kg/day phenytoin. At a dose of 150 mg/kg/day, the increase in serum ALP, osteocalcin and MAR was reversed. No significant differences in serum calcium, phosphorus, or 1,25(OH)2D3 levels were seen. In a second experiment, three groups of rats received daily I.P. injection of lower doses of phenytoin (i.e., 0, 1, or 5 mg/kg/day, respectively) for 42 days. Phenytoin also did not affect the growth rate or serum calcium, phosphorus, and 25(OH)D3 levels. Daily injection of 5 mg/kg/day phenytoin significantly increased several measures of bone formation, i.e., serum ALP and osteocalcin bone ALP, periosteal MAR, and trabecular bone volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796346 TI - Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha,25-dihydroxyvitamin D2. AB - Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 [24-epi-1 alpha(OH)D2], 24-epi-1 alpha,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1 alpha,24S,25-trihydroxyvitamin D2 [1,24S,25(OH)3D2], which might be a metabolite of 24-epi-1,25(OH)2D2, were investigated. In an in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was similar to that of 1 alpha hydroxyvitamin D3 [1 alpha(OH)D3] at 10(-9) M-10(-6) M. The activity of 24-epi 1,25(OH)2D2 was weaker than that of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] at 10(-11) M-10(-8) M. On the other hand, the activity of 1,24S,25(OH)3D2 was similar to that of 24-epi-1,25(OH)2D2 at 10(-11) M-10(-9) M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1 alpha(OH)D2 was weaker than that of 1 alpha(OH)D3 at 10(-7) M. The activity of 24-epi-1,25(OH)2D2 was almost similar to that of 1,25(OH)2D3 at 10(-11) M-10(-7) M. The activity of 1,24S,25(OH)3D2 was significantly weaker than that of 24-epi-1,25(OH)2D2 at 10( 11) M-10(-9) M. In the two experiments, the potencies of 24-epi-1,25(OH)2D2 were about 100 times higher than those of 24-epi-1 alpha(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was almost similar to those of 1 alpha(OH)D3 and 1,25(OH)2D3 and higher than those of 24-epi 1,25(OH)2D2 and 1,24S,25(OH)3D2. 24-epi-1 alpha-(OH)D2 and 1 alpha(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796347 TI - Menopause-related changes in bone mineral density in Japanese women: a longitudinal study on lumbar spine and proximal femur. AB - We investigated 2-year longitudinal changes of bone mineral density (BMD) in lumbar spine and proximal femur in 64 Japanese women aged 38-67. Forty subjects were premenopausal (mean age 44.9) and 24 postmenopausal (mean age 54.6) at enrollment of the study. Six subjects experienced menopause during the 2-year study period and were defined as the perimenopausal group. Measurements of BMD were performed using dual-energy X-ray absorptiometry at L2-4, femoral neck, greater trochanter, and Ward's triangle. Paired t test revealed no significant decrease in BMD at any site in the premenopausal group. Significant annual decrease in BMD was observed in the perimenopausal group at L2-4, femoral neck, and greater trochanter. A similar tendency was observed in Ward's triangle, but did not reach statistical significance. In the postmenopausal group, significant decrease in BMD was found at the proximal femur, but not at L2-4. Significant inverse correlation between age and change rate of BMD was found at L2-4, but not at the proximal femur, in premenopausal women. In postmenopausal women, there was a significant association between body weight (BW) change and change rate in BMD at L2-4, femoral neck, or greater trochanter. This association was not found in the premenopausal group. These results suggest that effect of menopause on BMD may be different in individuals and sites of the skeleton. BW change may affect change in BMD in postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796349 TI - Mineral concentration gradients in rat femoral diaphyses measured by X-ray microtomography. AB - The bone mineral concentrations of five rat femora were measured as a function of distance from the distal metaphysis by quantitative X-ray microtomography (XMT) at a resolution of approximately 23 x 23 x 15 microns3. Assuming the mineral phase of bone to be hydroxyapatite, Ca10 (PO4)6(OH)2, the mean cortical mineral concentration (CM) per transverse section was found to range from 1.33 to 1.47 g cm-3. Detectable variations in the bone mineral concentration between sections of femora from different animals could not be attributed to the age when the particular animal was sacrificed. An increase in CM with distance, L, from the distal growth plate was observed and a saturating exponential equation, CM = a - be-alpha L, was used to describe the changes. Each section of bone tissue was considered as a population of elementary volumes of bone (EVB) and L was related to the age of the EVB (TEVB). A simple model for the mineralization process of an EVB was then proposed. Each newly formed EVB accumulated mineral rapidly to give an initial mineral concentration of approximately 1.3 g cm-3 (parameter a-b). Their mineral concentrations then increased asymptotically to approximately 1.5 g cm-3 (parameter a) with a time constant of approximately 330 days. This slow maturation process is attributed to Ostwald ripening of the bone crystals with further crystal growth using ions from the extracellular fluid. PMID- 7796350 TI - The mandibular condylar growth center: separation and characterization of the cellular elements. AB - The developing mandibular condylar growth center consists of a number of histologically distinct cell types. There is an increase in cell volume that takes place from the condylar surface layer through the center of ossification, resulting in a disorganized, irregular cellular pattern. Consequently, the isolation and separation of the different cells from this tissue is difficult using standard methodologies. Countercurrent centrifugal elutriation, whereby cells are separated on the basis of size, was applied to bovine mandibular condylar growth center cells. The cell volume, alkaline phosphatase content, proteoglycan synthesis, and type X collagen synthesis all showed a positive correlation with increasing cell size. The largest cells had characteristics that are consistent with hypertrophic chondrocytes; the smallest cells, on the other hand, had many fibroblastic characteristics. PMID- 7796348 TI - Amylin increases bone volume but cannot ameliorate diabetic osteopenia. AB - Amylin is normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796351 TI - Effect of decalcification on bone mineral content and bending strength of feline femur. AB - The relationships between bone mineral content (BMC), bone calcium, and bone strength were studied in fractionally demineralized feline femurs. In 44 pairs of cat femurs, the right bones were decalcified in ethylene diaminetetra acetic acid (EDTA) to 20%, 40%, 60%, 80%, and 100% of the mineral content of the intact left bone (= control). The bones were then loaded to failure, and maximum strength values were recorded. The data were then used to calculate the percentage strength of the right relative to the left femurs. A correlation coefficient (r) of 0.970 was found between the percentage decalcification and percentage bending strength. A direct relationship (r = 0.876) was also observed between the total calcium extracted and total loss in BMC. The EDTA solutions were spot checked for protein content to determine if the organic matrices had been altered by demineralization. Protein was never detected. Nor did the demineralized tissues display histologic evidence of gross microscopic damage. This study has shown that in cat femurs, 20% decalcification led to about 35% loss in bending strength, and 60% decalcification caused 75% loss in strength. These values are significant as they highlight the importance of calcium to the strength of osteopenic bone. PMID- 7796354 TI - Assessment of dose and risk to the body following conventional and spiral computed tomography. AB - BACKGROUND: Computed tomography (CT) is one of the most frequently used examination procedures in diagnostic radiology and the dose given to the patients is higher than in general radiographic procedures. In this study LiF chip thermoluminescent dosimeters (TLD-100) were placed in each relative organ or tissue position, including head, chest and abdomen, in a Rando phantom. CT was performed using both conventional and spiral modes, and effective dose and effective dose equivalent were assessed for each organ or tissue scanned. METHODS: The TLD reader used in this experiment was controlled at a nitrogen flow rate of 450 ml/min, preheat time of 14 seconds, reading time of 16 seconds and annealing time of 16 seconds. This CT scanner can be used to perform both conventional and spiral tomography. Operating conditions for spiral tomography were 120 kV, 80 mA for scout film, and 120 kV, 200 mA, 1 sec/slice for each scanning. However, for conventional tomography, the operating conditions were 120 kV, 80 mA for scout film and 120 kV, 160 mA, 1.5 sec/slice for each scanning. These operating conditions are satisfactory to most clinical applications, and therefore were adopted for the present studies. RESULTS: Results showed that, in both effective dose and effective dose and effective dose equivalent, conventional tomography was higher than spiral tomography. The average effective doses for each part were measured to be 1.89 and 4.95 mSv for the head, 30.01 and 40.65 mSv for the chest, and 12.85 and 19.62 mSv for the abdomen of spiral and conventional CT, respectively. Higher carcinogenic risk was assessed in organs such as liver, lung, stomach and bone marrow, other organs had a relatively lower incidence of risk. CONCLUSIONS: The main purpose of this study was to obtain distribution values of effective dose and effective dose equivalent, and to know the probability of carcinogenic effect upon each organ or tissue after CT scanning. Results showed the average effective dose for spiral CT to be less than conventional CT, and the dose in the body surface was generally lower than the dose in the central region. PMID- 7796352 TI - A new rapid and reproducible homologous immunoradiometric assay for amino terminal parathyroid hormone in the rat. AB - Measurement of parathyroid hormone (PTH) in the rat is most often performed with competitive ligand radioimmunoassays (RIA) utilizing heterologous antibodies. We report here the validation of a newly developed homologous immunoradiometric assay (IRMA) for rat PTH. Two different goat antibodies to the amino-terminal sequence of rat PTH are utilized; one is immobilized onto plastic beads to capture the PTH molecules and the other is radiolabeled for detection. To test this new IRMA, 30 Sprague-Dawley rats were randomized into three treatment groups to receive by intraperitoneal injection: (1) saline 1 ml/kg (control); (2) calcium chloride 40 mg/kg (hypercalcemic); and (3) EDTA 300 mg/kg (hypocalcemic). Blood samples were taken at 0, 30, 60, 180, and 300 minutes after administration of the assigned treatment for measurement of ionized calcium (Ca2+) and serum PTH. Most of the variance in PTH levels was found to be due to changes in Ca2+ (r2 = 0.780, P < 0.0001). There was also a close temporal relationship between the two, with the highest levels of PTH occurring at the same measured time points as the lowest Ca2+, and vice versa. The measured detection limit of the IRMA was 3 pg/ml with intra- and interassay coefficients of variation of 1.74% and 3.07%, respectively. Serial dilutions with pooled rat serum, synthetic rat PTH-(1-34), and synthetic human PTH-(1-34) showed good parallelism with increased specificity for the pooled and synthetic PTH, despite a degree of crossreactivity with hPTH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796353 TI - Investigation of the relationship between osteoporosis and the collagenase gene by means of polymorphism of the 5'upstream region of this gene. AB - Osteoporosis is a slowly progressing disease resulting from an imbalance between bone accretion and degradation. As interstitial collagenase is a key enzyme in the degradation of bone matrix, we investigated a possible relationship between the collagenase gene and osteoporosis. Analysis of an amplified genomic DNA fragment from -524 to +52 by denaturing gradient gel electrophoresis and sequencing allowed us to detect three dimorphic sites upstream of base -300, one of them leading to a BanI restriction site. None of the sites could be directly associated with osteoporosis. The allele frequencies of the three dimorphic sites were estimated. The interallelic ratios were high, thus providing new useful genetic markers for linkage analysis. When comparing these ratios in osteoporotic and nonosteoporotic subjects, no significant differences could be observed. PMID- 7796355 TI - Gingival overgrowth induced by different dosages of cyclosporin in rats. AB - BACKGROUND: The purpose of the study was to assess the dose effect on the severity of cyclosporin(CSA)-induced gingival overgrowth by an established rat model. METHODS: A total of 60 Sprague-Dawley male rats which weights were about 250 gm were selected and randomly divided into four groups. Three experimental groups of rats were provided different gastric feedings of 3mg, 10mg, 30mg CSA per kilogram body weight, daily; the last group of rats was fed with mineral oil as the control. Stone impression models of the mandibular incisal region were taken and three-dimensional analyses of the overgrown gingiva were made biweekly. RESULTS: In the 30 mg CSA-treated rats, all three-dimensional measurements of the gingiva were observed to be greater than those of the control rats from the second week after CSA administration. In the 10 mg CSA-treated rats, most of gingival measurements were found to be greater from the fourth week after CSA administration. The bucco-lingual width of interdental papilla on the sixth week after CSA administration was the only significant measurement showing a difference between the 3mg treated rats and the control group. CONCLUSIONS: Because of a significant correlation between CSA-induced gingival overgrowth and CSA dosage, the dose effect on the severity of this gingival overgrowth was established in the rat model. PMID- 7796356 TI - Cytogenetic studies in de novo acute nonlymphocytic leukemia. AB - BACKGROUND: There is currently considerable interest in the cytogenetic analysis of leukemia. The improvement of banding techniques has made it possible to rather precisely identify deletion, translocation, inversions, and other structural chromosome abnormalities. Specific recurring chromosome abnormalities associated with distinctive morphologic features are thus increasingly recognized in acute nonlymphocytic leukemia. For example, uneven geographic distribution of nonrandom specific chromosome aberrations has been reported. We herein report the results of chromosome studies on 30 Chinese patients with de novo acute nonlymphocytic leukemia. METHODS: Cytogenetic studies were performed at Veterans General Hospital-Taipei, from 1988 to 1993, on unselected samples of 30 patients with de novo acute nonlymphocytic leukemia. Chromosome analysis was performed by short term culture techniques on bone marrow material obtained from patients at diagnosis. Metaphase chromosomes were banded by the conventional trypsin-Giemsa banding technique and then karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). Classification of leukemia was based on the criteria of the French-American-British cooperative group. RESULTS: Of the 30 patients with adequate specimens, 17 (56%) demonstrated clonal chromosome abnormalities. Six patients were found to have structural rearrangements and seven patients have a numerical change as the sole abnormality. Four patients showed both structural and numerical anomalies. t(8;21) was found in 1 of the 8 M2 type ANLL patients and two of them had monosomy 21. Four of the 6 patients with acute promyelocytic leukemia (APL; M3 subtype) showed t(15;17). Two patients with M4 type leukemia and abnormal bone marrow eosinophils showed inv(16)(p13q22). One patient with M4 type leukemia demonstrated the loss of chromosome #7 and none showed the loss or deletion of chromosome #5. CONCLUSIONS: This study revealed a consistent finding of t(15;17) in APL; however, a low incidence of t(8;21), -5/5q- and -7/7q- in our patients demonstrated the possible difference in the incidence of chromosomal abnormalities in ANLL between the oriental peoples and the whites. PMID- 7796358 TI - Complications of continuous ambulatory peritoneal dialysis: one surgeon's experience with 668 patient-month follow-up. AB - BACKGROUND: The technique of continuous ambulatory peritoneal dialysis (CAPD) catheterization is critical to patient success. To clarify how important a surgeon's experience to CAPD is, the experience exclusively from a single surgeon was presented and compared with those from a group of surgeons. The roles of intraoperative fluoroscopy and laparoscopy in CAPD catheterization and the rescue of tube migration in the authors' experience would also be introduced. METHODS: Fifty-five patients followed for a total of 668 patient-months between July 1990 and July 1993 were included for analysis. All of the catheterization procedures were done by one surgeon. RESULTS: The overall complication rate was 56%. Twenty two percent of the patients had peritonitis, with an incidence of 0.56/patient year, and 25% of the patients had exit-site infection, with an incidence of 0.36/patient-year. Tube migration occurred in two patients (4%). There was no dialysate leakage or incisional hernia. These incidences were much lower than previous reports by groups of surgeons. Laparoscopy successfully rescued a migrated tube. The cumulative 1-year, 2-year and 3-year catheter survival rates were 81%, 75% and 63% respectively. The previous abdominal operation, catheter type and catheterization site were not the prognostic factors of catheter survival. CONCLUSIONS: Based on this favorable outcomes, an experienced CAPD surgeon may be one of the factors in minimizing the complications and improving the catheter survival in CAPD. Intraoperative fluoroscopy for every catheterization procedure and laparoscopy for the migrated or dysfunctional tube are highly recommended. PMID- 7796357 TI - A randomized comparative study on the safety and efficacy of clarithromycin and erythromycin in treating community-acquired pneumonia. AB - BACKGROUND: Clarithromycin, a new macrolide, has distinct microbiological and pharmacokinetic advantages compared with erythromycin. This study was designed to compare the safety and efficacy of clarithromycin and erythromycin in the treatment of community-acquired pneumonia. METHODS: Forty adult patients, diagnosed with community-acquired pneumonia, were randomly arranged to received either clarithromycin 250 mg twice daily (20 patients) or erythromycin 500 mg four times daily (20 patients), over a period of 14 days each. RESULTS: There were no statistically significant differences between the two groups in terms of clinical cure (65% for clarithromycin, 65% for erythromycin), clinical success (clinical cure and improvement: 95% for clarithromycin, 90% for erythromycin) and radiological response (95% for clarithromycin, 90% for erythromycin). However, adverse effects, mainly gastrointestinal, were significantly higher among patients treated with erythromycin than among patients treated with clarithromycion (p < 0.05). CONCLUSIONS: These results demonstrate that clarithromycin 250 mg twice daily is at least as effective as erythromycin 500 mg four times daily for the treatment of community-acquired pneumonia, and is much better tolerated. PMID- 7796359 TI - Vecuronium dissolved in normal saline exaggerates pain on intravenous injection. AB - BACKGROUND: On some anesthetic occasions, many patients complained of pain at the site of injection when vecuronium, dissolved in normal saline, was administered intravenously. The aims of this study was to compare the incidence of pain on i.v. injection of vecuronium either dissolved in normal saline or in a solvent provided by the pharmaceutical manufacturer. METHODS: We studied eighty patients of ASA physical status class I-II undergoing elective surgery under general anesthesia. Patients were arranged randomly to receive intravenous 0.1 mg/kg vecuronium dissolved either in solvent (n = 40) or in normal saline (n = 40) through the catheter indwelling in a vein on the dorsum of hand over 5 seconds. Immediately after injection, a nurse was appointed to score the degree of pain. Induction of anesthesia was accomplished with thiopental and fentanyl 30 seconds after vecuronium administration. RESULTS: Vecuronium dissolved in normal saline induced severe pain more frequently during injection than that dissolved in solvent (27.5% versus 10%). There was no significant difference in pH between these two solutions (3.87 versus 4.08). However, vecuronium dissolved in normal saline showed higher osmolality than that dissolved in solvent (425 +/- 7 mOsm/kg versus 149 +/- 3 mOsm/kg). CONCLUSIONS: Pain resulting from intravenous injection of vecuronium can be aggravated if normal saline was used as the solvent. Increased osmolality may also be responsible for this phenomenon. PMID- 7796361 TI - Primary non-Hodgkin's lymphoma of the mediastinum: a clinicopathological report of six cases. AB - BACKGROUND: Primary mediastinal non-Hodgkin's lymphoma [NHL] predominates in young adult with diffuse large B-cell histologic characteristics, and favorable prognosis. Six patients with this disease were diagnosed and treated at the Tri Service General hospital during the period of 1986 to 1991. METHODS: Pathology data were reviewed. All cases were classified according to the International Working Formulation. All specimens were studied immunohistologic for immunoglobulin kappa and lambda light chains, common leukocyte antigen (CLA), B cell marker (L26) and T cell marker (MT1 & UCHL1). All patients were treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) and adjuvant radiotherapy. RESULTS: Most of the patients were young adults with bulky disease in the anterior mediastinum. All presented with symptoms attributed to a rapidly growing mass. Four patients had superior vena cava syndromes. The histologic types were B-cell type lymphoma, including immunoblastic cell in two, and diffuse large cleaved cells in four patients. Three were in stage II and the others were in stage IV. Complete response was achieved in four patients and partial response in two, with an overall response rate of 100%. CONCLUSIONS: The results suggest that primary non-Hodgkin's non-lymphoblastic lymphoma commonly occurs in young adults and had an associated aggressive clinical course. In view of these results, observation have also suggested that intensive chemotherapy and bone marrow transplantation are needed for patients who relapse or fail to get complete remission. PMID- 7796360 TI - Ipratropium bromide and intraoperative bronchospasm. AB - BACKGROUND: Ipratropium bromide (IB) is a synthetic anticholinergic bronchodilator which is effective when administered by inhalation. Therefore, IB may be effective for the management of intraoperative bronchospasm. This study was designed to evaluate the effects of inhaled IB in the management of intraoperative bronchospasm induced by endotracheal intubation. METHODS: Nine asthmatics who were asymptomatic preoperatively were investigated. They developed bronchospasm after endotracheal intubation. IB 120 micrograms was aerosolized through the endotracheal tube. Heart rate, peak inspiratory pressure (PIP), airway resistance (Raw) and pulmonary resistance (Rpul) before and after IB administration were recorded and calculated. RESULTS: IB 120 micrograms relieved wheezing in 11 +/- 4 min (mean +/- SD), and significantly decreased PIP in 5 min and reached peak effects at 120 minutes after administration. Raw and Rpul also decreased during similar time intervals. Heart rates had no significant change after IB administration. CONCLUSIONS: The present study indicated that IB 120 micrograms could abate the intraoperative bronchospasm caused by airway hyperreactivity induced by endotracheal intubation in preoperatively asymptomatic asthmatic patients, and may have a role in the management of intraoperative bronchospasm. PMID- 7796363 TI - Spontaneous tendon rupture in rheumatoid hand-successful reconstruction with tendon transfer: a case report. AB - Rheumatoid arthritis is not as common a problem in Taiwan as it is in western countries. Compared with traumatic tendon rupture, tendon rupture in rheumatoid arthritis has its complex and peculiar pathophysiological mechanism which includes chemical erosion by hypertrophic synovium and mechanical attrition by deformed joints and bony spurs. In management, all these pathological foci must be eradicated to prevent recurrent failure. Tendon transfer is a simple and effective method for reconstructing lost tendon function. PMID- 7796364 TI - Pulmonary carcinoid tumor--tumorlet type: a case report. AB - A rare case of bronchiectasis with carcinoid tumor, tumorlet type, is reported. The patient was a 53-year-old female who underwent lobectomy of the right middle and lower lobes for severe hemorrhage secondary to bronchiectasis. No tumor was seen on chest X-ray or by gross examination of the lung. Microscopically, there were multiple tumorlets in the pulmonary parenchyma surrounding the bronchiole and small bronchus. The tumor cells stained positive for neuron-specific enolase, keratin and chromogranin stain. The morphology, and staining properties suggested that the pulmonary tumorlets were carcinoid tumor. No tumor cells were identified in the four peribronchial lymph nodes. The patient is disease-free after four years of follow-up. PMID- 7796362 TI - Congenital muscular dystrophy (non-Fukuyama type): a case report. AB - A Taiwanese girl, aged 12 years, presented with early myogenic hypotonia, multiple joint contractures, mental subnormality and epilepsy. Computerized tomography scanning of the brain showed white matter hyperlucency. According to her clinical manifestations and radiological pictures, the patient could be the fourth oriental case who had the features of occidental-type cerebromuscular dystrophy. PMID- 7796365 TI - Mesoblastic nephroma: a case report. AB - Mesoblastic nephroma is a rare tumor of kidney characterized by interlacing bundles of spindle mesenchymal cells. The tumor usually occurs in the newborn, and scarcely in the old child. In this article, the authors report a case of an unusual age, a 12-year-old boy, with mesoblastic nephroma which was found by routine physical examination. PMID- 7796366 TI - Therapeutic computing: teaching therapeutic communications utilizing a videodisc. AB - Effective communication skills for nurses are essential and serve as the interface between patients and health care providers. Yet, teaching communication skills is subject to only limited success. Results vary according to the mix of students, the talent and interest of the instructor, and the availability of teaching time for the topic. The nursing program at Indiana University Kokomo is addressing the needs of nursing students with a multimedia computer system. A videodisc on therapeutic communication was purchased to supply the desired video based examples. The programming of the computer interface was done by a senior information systems department major. Student attitudes measured after using the system the first year were very good. PMID- 7796367 TI - A psychometric examination of the Stronge-Brodt Nurses' Attitudes Toward Computers Questionnaire. AB - The purpose of this study was to examine the factor structure and reliability of the Stronge-Brodt Nurses' Attitudes Toward Computers Questionnaire. The instrument was administered to nurses before (T1, n = 391) and after (T2, n = 265) the implementation of a computerized patient care information system. A factor analysis of each sample was carried out using the SPSS/PC+ factor procedure with varimax rotation and Kaiser normalization. The factor analyses for T1 and T2 were consistent and identified three factors that parallel those generated in a factor analysis performed by Schwirian et al (1989). In both samples of the current study, the internal consistency reliability for the first factor was high (T1 alpha = .91, T2 alpha = .92), whereas the second and third factors demonstrated diminished reliability. Overall instrument reliability was .93 at T1 and .92 at T2. This study, with relatively large sample sizes, provided further clarification of the factor structure and supported the high reliability of the instrument. PMID- 7796368 TI - The who, what, where, when, and how of computer education. AB - Using a "Who, What, Where, When, and How" approach, the author addresses multiple issues that must be considered during computer education planning and development. The nursing department usually has the largest number of people requiring computer education and their training must be coordinated with other departments, so a well-thought-out training plan is required. This article presents practical hints and helpful strategies for developing such a plan. PMID- 7796369 TI - Applied information technology: a clinical perspective. Feature focus: the computer-based patient record (Part 2). PMID- 7796370 TI - Implementation of a variety of computerized bedside nursing information systems in 17 New Jersey hospitals. AB - This article examines issues of implementing nursing information computer systems in 17 hospitals in New Jersey and the initial effects of such systems as perceived by users. Unlike previous studies that examined the effects of one system in one hospital, this study examines the effects of several major systems in a variety of settings. Many of the hospitals experienced major delays or other problems with implementation; the hospitals in which timely implementation occurred were the ones that had purchased a commercially available stand-alone nursing system and did not try to develop interfaces or do extensive development. While these hospitals did meet with difficulties and needed some software customization, the problems were not so severe as to impede timely implementation. On the other hand, most of the hospitals that had major delays had planned more ambitious projects. These hospitals either required development work with vendors or were implementing a nursing information system while simultaneously putting in place a hospital system. Initial staff impressions of the effects of the system were positive; nursing department staffs reported that they liked the nursing systems. They said that documentation was better (more readable, complete, and timely) and they also believed that care was improved because the computer prompted nurses on what to look for and what to do. Support for these systems from hospital administration, outside of nursing, was cautious and based primarily on cost/benefit results. PMID- 7796371 TI - Health care costs: hospital-bed view versus the larger picture. PMID- 7796372 TI - Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada. AB - OBJECTIVE: To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. OPTIONS: Hospital care, home care, single-provider care and multidisciplinary care. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should be enrolled in a home self-infusion program. Patients with hemophilia and von Willebrand's disease should wear or carry Medic Alert identification. They should be vaccinated against hepatitis B and attend for routine follow-up examinations. Laboratory testing should be carried out as required, and dental and surgical care should be undertaken in consultation with a hematologist. VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. PMID- 7796373 TI - Complementary health care services: a survey of general practitioners' views. AB - OBJECTIVE: To determine the referral practices, perceived usefulness, knowledge, prior training and desire for training of general practitioners (GPs) in Quebec with regard to complementary health care services such as acupuncture, chiropractic and hypnosis. DESIGN: Cross-sectional mail survey. SETTING: Province of Quebec. PARTICIPANTS: Random sample of 200 GPs. Of the 146 who responded, 25 were excluded because they were no longer in practice; this left 121 (83%). OUTCOME MEASURES: Self-reported referral practices for complementary health care services, perceived usefulness and self-assessed knowledge of such services, and prior training and desire for training in these services. RESULTS: Sixty percent (72/121) of the GPs knew at least one practitioner of a complementary health care service for referral; 59% (70/119) reported referring patients to physicians who practise such services and 68% (80/118) to nonmedical practitioners. At least one of the three services studied were regarded as having some use by 83% (101/121). Overall, self-reported knowledge was poor: the proportions of GPs who reported knowing a lot about acupuncture, chiropractic and hypnosis were 11% (13/121), 10% (12/121) and 8% (10/121) respectively. Prior training was also lacking: only 8% (9/118) of the GPs had received previous training in acupuncture, 2% (2/111) in chiropractic and 3% (3/103) in hypnosis. In all, 48% (57/118) indicated that they would like further training in at least one of the services studied, and 13% (16/121) indicated that they currently provided one service. CONCLUSIONS: Referral of patients by GPs to practitioners of complementary health care services is common in Quebec. Although self-assessed knowledge about such services is relatively poor, interest in learning more about them is high. These findings identify a demand for future educational initiatives. PMID- 7796374 TI - Frequent users of ambulatory health care in Quebec: the case of doctor-shoppers. AB - OBJECTIVE: To examine the patterns of use of ambulatory care in Quebec in 1991, with special emphasis on patients who received care from more than 20 physicians. DESIGN: Retrospective study of population-based data. SETTING: Province of Quebec. PARTICIPANTS: All 7,154,591 people eligible for coverage under the Regie de l'assurance-maladie du Quebec (RAMQ) (Quebec Health Insurance Plan) in 1991, including 3639 people who received ambulatory care from more than 20 physicians. DATA EXTRACTION: The databanks of the RAMQ. OUTCOME MEASURES: Mean number (and standard deviation) of physician visits and services received, place of visit (clinic or private office), mean cost of services, patient's age, diagnosis, type of specialist visited and social assistance status of frequent users. RESULTS: The patients who obtained ambulatory care from more than 20 physicians received 10 times more medical services than the overall patient population (59.6 v. 5.8), and the mean cost per patient for ambulatory care was also 10 times higher ($1379 v. $136). Almost all of the frequent users visited at least one outpatient clinic, as compared with 37.3% of the overall population. A higher proportion of the frequent users than of the overall population obtained care from specialists (98.9% v. 54.7%), mainly general surgeons and psychiatrists. The most frequent diagnoses among the frequent users were anxiety (36.0%), abdominal pain (24.3%), drug or alcohol dependence (22.2%) and depression (16.4%). CONCLUSIONS: A small proportion of the population obtained ambulatory care from a high number of physicians during the year, leading to high expenses. Identifying and understanding this type of frequent user may be useful in developing strategies to promote more effective health-care-seeking behaviours and reduce overuse. PMID- 7796375 TI - Integrating complementary medicine and health care services into practice. AB - Complementary medicine and health care services constitute a significant proportion of the use of health care services in Canada, despite a history of limited acceptance of these therapies by the medical profession. However, physician attitudes appear to be changing. A survey of a random sample of general practitioners in Quebec (see page 29 of this issue) shows that four out of five general practitioners perceive at least one of three complementary health care services to be useful. Similar surveys of samples in Alberta and Ontario suggest that physicians there, although somewhat less enthusiastic than their counterparts in Quebec, have also begun to be more open-minded about these types of therapies. However, physicians have reported little understanding of complementary health care services, which suggests the need for more research on and education about these services. The Medical Society of Nova Scotia has responded to this need by establishing a Section of Complementary Medicine. The authors believe that fair, accountable, scientific and rigorous research on complementary therapies will benefit physicians and patients. The problems inherent in applying reductionist analysis to a holistic approach to care can be largely circumvented by focusing on outcomes research. In light of the popularity of these therapies, inquiry into patient use of complementary health care services should become a part of a complete patient history. This measure would promote greater patient-physician communication and integration of complementary health care services into patient care. PMID- 7796376 TI - Laboratory reports of human viral and selected nonviral agents in Canada--1993. PMID- 7796377 TI - Debate about parents' right to spank causes divisions among MDs. AB - Does spanking involve child abuse, or is it an acceptable form of discipline in Canada? Section 43 of the Criminal Code allows "reasonable" force on the part of a teacher or parent as a disciplinary measure, but an advocacy group believes that this section of the code should be repealed. However, a recent court case indicates that abolition of corporal punishment is not a black-and-white issue. PMID- 7796378 TI - Barer and Stoddart revisit the issue of funding academic health centres. AB - Four years after Drs. Morris Barer and Greg Stoddart presented their landmark report, Toward Integrated Medical Resource Policies for Canada, to the country's deputy ministers of health, not much progress has been reported on the reformation of Canada's academic health centres. A recent survey of respondents consulted for the original report showed "a deafening lack of responses" that indicated the situation has improved since the report was issued. Government respondents had a more positive opinion than administrators of the centres. PMID- 7796379 TI - Canada must be alert to threat of imported wild poliovirus, working group says. AB - Even though the Western Hemisphere is certified as being polio free, countries such as Canada must be alert to the continuing threat posed by the importation of wild poliovirus from polio-endemic regions, according to a report from Canada's Working Group on Polio Eradication and the Laboratory Centre for Disease Control. The working group recommends the maintenance of high immunization-coverage levels and strengthened surveillance activities for polio. PMID- 7796381 TI - The brave new world of managed care. AB - Canadian hospitals that think they can charge higher-than-normal rates to foreign visitors are learning a lesson as US-style managed care moves north of the border. Dr. Robert MacMillan, president and medical director of Florida-based Insurance Claims Management Systems and past president of the Ontario Medical Association, says that south of the border US-style managed care has already hauled in the reins on wild expectations about high payments, and it is expected to do the same for Canadian hospitals that charge private insurers "as much as the traffic will bear." He says it is no longer uncommon for a large Toronto hospital to charge a foreign patient $3000 a day for care that can now be purchased in a US hospital for one-third that price. PMID- 7796380 TI - After years of steady growth, winds of restraint blowing on prescription-drug industry. AB - Tough fiscal times are forcing cutbaks in many areas of health care, and the prescription-drug industry is no exception. The Pharmaceutical Manufacturers Association of Canada says Canada's brand-name drug companies face two major hurdles: restricted market access, as drug formularies limit the number of new drugs, and restricted price increases, as allowed by the Patented Medicine Prices Review Board and provincial formularies. The Canadian Drug Manufacturers Association, which represents Canada's generic-drug industry, says its message to physicians is that generic products are important agents of cost control and that the health care community is more aware of this than it once was. "If you don't maximize your savings while you can," cautions the association's Brenda Drinkwalter, "you'll never be able to afford the high-priced drugs of tomorrow". PMID- 7796382 TI - Indoor air quality a major public-health issue, workshop told. AB - Indoor pollution is a major public-health issue, say representatives from government and the medical profession who participated in a recent workshop in Ottawa. Researchers are certain that indoor pollution causes many of the allergy related problems and asthma, bronchitis, rhinitis, coughing and others respiratory problems experienced by North Americans. They urge physicians to learn about indoor air quality and to educate patients to improve their environment, particularly with respect to second-hand smoke, dust mites and mould. PMID- 7796383 TI - Spas accepted part of health care in Czech Republic. AB - Although the days are gone when a spa holiday was offered as a reward to Communist Party leaders and factory workers who exceed their quotas, spas are still popular in the former Czechoslovakia. Government health care coverage relating to spas extends to fewer medical conditions and may not cover the expense of room and board, but more patients are footing the bill themselves, even though a 3-week stay costs more than the average monthly earnings. Officials predict spas will prosper under new private health insurance plans and expanding consumer spending power. PMID- 7796384 TI - Fusion between enveloped viruses and erythrocyte membranes is induced by the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane). AB - Pristane (2,6,10,14-tetramethylpentadecane) is an isoprenoid alkane that induces plasma cell tumors in mice. Infection with certain retroviruses accelerates tumorigenesis but the nature of the cooperation between pristane and viruses is unknown. The purpose of this study was to investigate the potential influence of pristane on the fusion between enveloped viruses and mammalian plasma membranes. Using a fluorescence dequenching assay, we found that micromolar amounts of pristane induced fusion between erythrocyte membranes and both vesicular stomatitis virus and influenza virus. Induction of fusion occurred with as little as 5 microM pristane and reached saturation at roughly 50 microM alkane. Control experiments revealed that induction of fluorescence dequenching was not due to extraneous phenomena such as lipid transfer or non-specific interactions with the carrier for pristane (beta-cyclodextrin). Fusion was also induced by standard protocols which involve lowering the pH of the incubation medium. In the presence of pristane, low pH-triggered fusion was enhanced. The extent to which pristane induced fusion was dependent upon the orientation of the lipids in the target membrane. That is, fusion was most effective with erythrocyte ghosts which had a symmetric lipid distribution and was less effective with ghosts in which the native lipid asymmetry was maintained. Intact erythrocytes, which have an asymmetric lipid distribution, were the least effective targets. This result exactly parallels the pattern observed with acid-induced fusion. Similar patterns were also observed in the temperature dependence of fusion induced by these two protocols. The novel fusogenic activity of pristane is discussed with regard to current models of virus/membrane fusion. PMID- 7796385 TI - Increase in postirradiation survival of rat 3Y1 fibroblasts by a protein kinase inhibitor, staurosporine. AB - Protein kinases play an important role in the response of mammalian cells to ionizing radiation. In this study, we examined the effect of staurosporine, a potent inhibitor of protein kinases, on cell survival after X-irradiation, using the normal rat fibroblast line 3Y1. Treatment with 30 ng/ml staurosporine 1 h before irradiation resulted in the increase in survival of 3Y1 cells. This phenomenon was drug dose-dependent and maximal reduction of radiation-induced cell killing occurred when more than, or equal to, 30 ng/ml staurosporine was added. In contrast, treatment with 30 ng/ml staurosporine after irradiation did not increase cell survival. There was no change in cell cycle distribution by treatment for 1 h with 30 ng/ml staurosporine. These data suggest that the inhibition of protein kinase activities by staurosporine influences the radiosensitivity of 3Y1 cells. PMID- 7796386 TI - On the relationship between rate of uptake of Photofrin and cellular responses to photodynamic treatment in vitro. AB - The Burkitt's lymphoma cell line Namalva was used as an in vitro model to study the accumulation and photocytotoxic properties of Photofrin, the photosensitizer currently in clinical trials. Photofrin uptake and intracellular protein binding were evaluated as a function of the incubation time using fluorescence spectroscopy. The drug concentration strongly affected the intracellular distribution pattern of Photofrin, which in turn was shown to correlate with the Namalva cell response to photodynamic action. At low drug load, a gradual cell response varying from transient cell cycle arrest (predominantly S-phase) to marked photocytotoxicity modulated by incubation time and light dose was observed. High drug load resulted in lethality without cell cycle selectivity. The data suggest possible Photofrin targeting of protein factors involved in cell proliferation. PMID- 7796387 TI - Mucin coding sequences are remarkably conserved. AB - Mucins are complex glycoproteins expressed by glandular epithelia and the carcinoma which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucins, which also contains epitopes recognized by T cells from pancreatic and breast cancer patients. Based on the PCR amplification of the mucin coding sequences, hybridization analysis and determination of the sequence divergence we present the evidence that mucin coding sequences are conserved in a number of species. A broad series of organisms were examined for analogous sequences. Data show that mucin-type sequences are present in a variety of mammals, but less apparent in chicken and yeast. Divergence increased in the order human, monkey, rabbit/rat/cow, mouse; chicken and yeast exhibited minimal homology. Furthermore, nucleotide sequences not included in the tandem repeats, a common feature of mucin core structure, are more conserved than the flanking sequences which also suggests that the flanking sequences may be functionally significant while repeats are structurally important. The hybridization bands showed different restriction patterns (suggesting for the existence of the restriction fragment length polymorphism). Northern analysis indicates message polydispersity, commonly seen with this class of RNA. The major features of the protein appear broadly conserved in the different mammalian species examined. The evolutionary significance of the above studies has been discussed. PMID- 7796389 TI - Relationship between the levels of purine salvage pathway enzymes and clinical/biological aggressiveness of human colon carcinoma. AB - A large series of samples obtained after surgical resection of intestinal mucosa of patients affected by intestinal carcinoma was examined in order to define possible relationships between levels of enzymes involved in the purine salvage pathway and clinical/biological parameters of aggressiveness and invasiveness. The results confirm our previous observation on a different pattern of purine salvage enzymes in tumor as compared to normal colon tissues (Camici et al., 1990). In fact, we observed in human colon tumor tissues a significant enhancement of the three enzymes involved in the synthesis of IMP, hypoxanthine guanine phosphoribosyltransferase (HGPRT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). On the other hand, no variation was observed in the 5'-nucleotidase and alkaline phosphatase activities. While we could not find a significant correlation between HGPRT, ADA and PNP activities and histologic grading or biological parameters of tumor aggressiveness, the significant correlation with the extent of disease, as expressed by the Dukes' stage, would demonstrate at least for human colon tumors, a relationship between enzyme activity and tumor invasiveness. PMID- 7796388 TI - Leukocyte arylsulphatase A activity in acute leukemia. AB - Lysosomal arylsulphatase A of peripheral leukocytes from patients with acute lymphoblastic and myeloblastic leukemia and from healthy subjects, were studied. Arylsulphatase A activity of both types of leukemic cells was significantly higher than those of cells from healthy subjects. From our present observations, it can be concluded that estimation of lysosomal arylsulphatase A of leukocytes, may be of value clinically as a biochemical assay which can serve to demonstrate the presence of malignancy. PMID- 7796390 TI - Inhibition of x-ray induced transformation and effect on myc and fos gene expression by the nucleotide analog, 2-aminopurine. AB - Ionizing radiation is a carcinogen that is known to induce malignant transformation of C3H/10T1/2 fibroblasts in vitro. Radiation is also known to induce c-myc expression and protease inhibitors that suppress radiation transformation reduce myc and fos gene expression. The antiproliferative protein kinase inhibitor 2-aminopurine has been shown to selectively inhibit serum induced c-fos and c-myc expression in human hemopoetic cells. The myc and fos oncogenes are thought to play a role in the regulation of cell proliferation and may be involved in early stages of carcinogenesis. We determined the ability of 2 aminopurine to affect x-ray-induced transformation in C3H/10T1/2 cells in vitro and its effect on myc and fos gene expression in these cells. Treatment with 2 aminopurine (5 x 10(-4) M) resulted in a 50-100% reduction in transformation yield when C3H/10T1/2 cells were irradiated with 6 Gy of x-irradiation. The 2 aminopurine had to be present during the post-confluent stage of cell growth in order to exert its inhibitory effect. Treatment of cells with 2-aminopurine significantly reduced the level of myc gene expression; the inhibitory effect of 2-aminopurine on fos gene expression in these cells was not statistically significant. PMID- 7796391 TI - Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. AB - Sporadic and familial malignant melanoma susceptibility has been linked to defects in the chromosomal region 9p21. Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 (CDKN2) or p16 gene, has been shown to be deleted, mutated, or rearranged in a high percentage of sporadic melanoma cell lines, as well as mutated in the germline of a proportion of familial melanoma patients. CDKN2 encodes a M(r) 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G1 phase of the cell cycle. Thus, mutations or deletions of the CDKN2 gene could result in abnormal proliferation via defective cell cycle control. The correlation of 9p21 cytogenetic and molecular alterations with the clinical stages of melanoma progression suggests that dysfunction of a gene within this chromosomal region is critical to the evolution of melanoma. However, it remains unclear whether this gene is the CDKN2 gene. If so, then loss of p16 is potentially an initiating or early event in melanoma progression. To address the issues of what is the potential involvement of the CDKN2 gene in sporadic melanoma and precisely when during the clinically evident stages of melanoma progression defects in CDKN2 occur, we have evaluated by immunohistochemistry the expression of p16 protein in 103 melanocytic lesions representing all stages in the progression of melanoma. Our results suggest that loss of p16 protein expression is (a) not necessary for tumor initiation in malignant melanoma because all melanomas in situ and the majority of primary invasive melanomas retain expression of this protein; and (b) potentially more related to invasiveness or the ability to metastasize, because 52% of primary invasive tumors and 72% of metastatic lesions show partial or complete loss of expression of p16. PMID- 7796392 TI - Evidence against dominant negative mechanisms of intestinal polyp formation by Apc gene mutations. AB - Mutations in the adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Most mutations found in familial adenomatous polyposis patients are of the truncation type, and the phenotype is affected by the mutation sites in the gene. Truncated APC proteins can associate with the wild-type protein. Accordingly, it has been proposed that the polyposis is caused by a dominant negative mechanism. To test this possibility, we constructed transgenic mice that contained mutant minigenes. They expressed the APC protein truncated either at codon 716 (Apc delta 716) or 1287 (Apc delta 1287) at high levels in the intestinal epithelium. Contrary to our expectation, no intestinal polyps or tumors were found in any of such mice, even after 7 months. These results rule out any dominant negative mechanisms in which the truncated APC protein is directly involved in the formation of intestinal polyps in the mouse. PMID- 7796394 TI - A variant glucocorticoid receptor messenger RNA is expressed in multiple myeloma patients. AB - In multiple myeloma cells resistant to glucocorticoids, we have previously identified a variant glucocorticoid receptor (GR) transcript (P. A. Moalli et al., Cancer Res., 53: 3877-3879, 1993). Here, we report a reverse transcription PCR assay to assess whether this aberrant GR transcript is present in myeloma patients. We detected both the wild-type and variant GR transcripts in the patient isolate that was the source of our myeloma cell lines, in patients refractory to steroid treatment, and in healthy control subjects. Simultaneous amplification of wild-type and variant GR mRNAs indicates that the variant GR is more highly expressed in cells that are resistant to glucocorticoids. We hypothesize that the variant GR is a normal mRNA transcript that acts to modulate glucocorticoid responsiveness, and increased expression contributes to a resistant phenotype. PMID- 7796393 TI - Transcriptional activation of the proto-oncogene c-jun by asbestos and H2O2 is directly related to increased proliferation and transformation of tracheal epithelial cells. AB - Asbestos causes persistent increases in c-jun mRNA and AP-1 DNA binding activity in hamster tracheal epithelial (HTE) cells, the progenitor cell type of asbestos induced bronchogenic carcinoma. Studies here were designed to determine mechanisms of c-jun induction by asbestos and the phenotypic consequences of Jun expression in HTE cells. To examine whether asbestos or H2O2 induced transcription of c-jun, we transiently transfected HTE cells with a plasmid containing a fragment of the c-jun promoter coupled to a luciferase reporter gene. In addition, c-jun was overexpressed in cells using a full-length human c jun construct, and effects on proliferation and transformation were examined. HTE cells transfected with the jun-luciferase construct showed increased luciferase activity when exposed to crocidolite asbestos or H2O2. These results demonstrate that asbestos and H2O2 activate AP-1-dependent gene transcription. Overexpression of c-jun led to increased proliferation and enhanced ability of HTE cells to grow in soft agar, an indication of cellular transformation. Data suggest that overexpression of c-jun may contribute to asbestos and oxidant-induced proliferation and carcinogenesis. PMID- 7796395 TI - Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas. AB - Telomerase activity was examined in 105 frozen samples from human normal liver tissues, chronic liver disease, and hepatocellular carcinoma (HCC). Telomerase activity was positive in 28 of 33 HCC tissues regardless of tumor stage or size. Telomerase was expressed in 15 of 18 differentiated HCC nodules smaller than 3 cm. HCC tissues from all eight hepatitis B virus-positive patients were telomerase positive, while telomerase activity was not detected in normal liver tissues (0 of 4). Weak telomerase activity was only detected in 1 of 22 nontumor liver tissues from HCC patients. Interestingly, in 19 of 38 hepatitis tissues and 6 of 8 cirrhotic liver tissues from apparently cancer-free patients, very weak telomerase activity was detected. These results indicate that the expression of telomerase may play a crucial role in hepatocarcinogenesis. PMID- 7796396 TI - Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. AB - We have developed a PCR approach to clone new apoptotic Ced-3/Ice-like cysteine protease genes. This approach uses degenerate oligonucleotides encoding the highly conserved pentapeptides QACRG and GSWFI that are present in all known apoptotic cysteine proteases. Using this approach, we have cloned a novel apoptotic gene from human Jurkat T lymphocytes. The new gene encodes a approximately 34-kilodalton protein that is highly homologous to human CPP32, Caenorhabditis elegans cell death protein CED-3, mammalian Ich-1 (Nedd2), and mammalian interleukin-1 beta converting enzyme. Because of its high homology to the C. elegans Ced-3 gene, we named the new gene mammalian Ced-3 homologue Mch2. Two Mch2 transcripts (Mch2 alpha, 1.7 kb; Mch2 beta, 1.4 kb) were detected in Jurkat T lymphocytes and other cell lines. We believe that the Mch2 alpha transcript encodes the full-length Mch2, whereas the Mch2 beta transcript encodes a shorter Mch2 isoform, probably as a result of alternative splicing. Like interleukin-1 beta converting enzyme and CPP32, recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity, as determined by its ability to cleave the fluorogenic peptide DEVD-AMC. CPP32 and Mch2 alpha can also cleave poly(ADP ribose) polymerase in vitro, suggesting that these enzymes participate in poly(ADP-ribose) polymerase cleavage observed during cellular apoptosis. In addition, overexpression of recombinant Mch2 alpha, but not Mch2 beta, induces apoptosis in Sf9 insect cells. Our data suggest that Mch2 is a Ced-3/interleukin 1 beta converting enzyme-like cysteine protease and could be another important mediator of apoptosis in mammalian cells. PMID- 7796397 TI - Ovarian carcinoma-associated TaqI restriction fragment length polymorphism in intron G of the progesterone receptor gene is due to an Alu sequence insertion. AB - Alu sequences, short, repetitive transposable DNA elements, are factors in a number of genetic diseases. We previously identified a germline TaqI RFLP, located in intron G of the human progesterone receptor gene, that showed an association with the incidence of sporadic ovarian carcinoma. Furthermore, the polymorphism was characterized as a small (approximately 300-bp) insertion that was inherited in a Mendelian fashion. Because of its insertional character, we named this polymorphism PROGINS. We report the identification of PROGINS as a 306 bp Alu element of the PV or HS-1 Alu subfamily. PMID- 7796398 TI - Loss of wild-type p53 bestows a growth advantage on primary cortical astrocytes and facilitates their in vitro transformation. AB - Primary cortical astrocytes were isolated from normal (+/+), heterozygous (+/-), or homozygous (-/-) p53-knockout mice. The normal astrocytes grew slowly and underwent crisis after limited division, while the homozygously defective cells grew rapidly and without contact inhibition. These -/- cells could not initially form colonies in soft agarose but acquired this capability after 10 passages in FCS or basic fibroblast growth factor but not epidermal growth factor. Almost all -/- astrocytes weakly expressed glial fibrillary acidic protein at passage 10 and were also A2B5+ when cultured in basic fibroblast growth factor. Most heterozygous cells resembled normal ones; however, some survived crisis, grew rapidly, and formed colonies. Outgrowing cells had all lost the wild-type p53 allele. These molecular and cellular events mimic the early stages of human brain tumors, suggest a role for p53 in the earliest stages of disease progression, and provide an experimental system to analyze the effects of other tumor-specific mutations in the disease process. PMID- 7796399 TI - Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. AB - The focal adhesion kinase (FAK) gene encodes a tyrosine kinase (p125FAK) thought to be involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because alterations in these cellular processes occur in tumor invasion and metastasis, we studied the protein expression of FAK in a variety of human tumors and found that in the 119 samples studied, increased levels of p125FAK correlated with the invasive potential of a tumor. By comparing FAK expression in tumors with normal tissue from the same patient, we found that p125FAK was significantly elevated in 17 (100%) of 17 invasive and metastatic colonic lesions and in 22 (88%) of 25 invasive and metastatic breast tumors. Additional studies of FAK expression in 13 high grade sarcomas showed high levels in all samples compared to benign, noninvasive mesenchymal specimens. Furthermore, FAK protein levels were elevated in preinvasive lesions, such as large (> 2 cm) colonic villous adenomas, whereas noninvasive, yet hypercellular, neoplastic tissues such as parathyroid and hepatocellular adenomas did not overexpress FAK. These data provide evidence that both epithelial and mesenchymal tumor progression are accompanied by increased p125FAK expression and suggest that the level of FAK expression might be a marker for the invasive potential of a tumor. PMID- 7796400 TI - Mutations of p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in biliary tract cancers. AB - p16Ink4 and p15Ink4B are cyclin-dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells. The genes encoding these inhibitors are located at 9p21, which is a frequent site of allelic loss in various types of tumors. Twenty-five primary biliary tract cancers were examined for somatic mutations in p16Ink4/CDKN2, p15Ink4B/MTS2, p53, and K-ras genes and allelic loss of 9p21 by microsatellite analysis. Four biliary tract cancer cell lines were analyzed for homozygous deletions and point mutations. We found frequent homozygous deletions in p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in the biliary tract cancer cell lines. Each cancer cell line had alteration of either p16Ink4/CDKN2, p15Ink4B/MTS2, or p53 genes. In primary tumors, 16 of 25 (64%) biliary tract cancers had point mutations in the p16Ink4/CDKN2 gene. These include 14 missense and 2 silent mutations. The frequency of mutations in gall bladder cancer and hilar bile duct cancer were 80% (8 of 10) and 63% (5 of 8), respectively. Each of codons 1, 80, and 111 was changed in two cases of these cancers. One of three intrahepatic bile duct cancers, one of two common bile duct cancers, and one of two ampullary cancers had mutations in the p16Ink4/CDKN2 gene. In contrast, no mutation in the p15Ink4B/MTS2 gene, one base change in the K-ras gene, and one loss of heterozygosity at the IFN alpha locus in 25 cancers and one base change in the p53 gene in 19 cancers were observed. These results suggest that p16Ink4/CDKN2, rather than p15Ink4B/MTS2 or p53 genes, and its inactivation may be important in biliary tract carcinogenesis. PMID- 7796402 TI - Mucosa-preferential DNA adduct formation by 2-amino-3-methylimidazo-[4,5 f]quinoline in the rat colonic wall. AB - The mechanism of mucosa-specific formation of DNA adducts, which was found recently in human intestines, was studied in male F344 rats treated with 2-amino 3-methylimidazo[4,5-f]quinoline (IQ). There are three conceivable pathways for p.o. administered IQ to reach the target colonic mucosal cells: pathway 1, through the digestive canal which exposes from the lumenal direction; pathway 2, following enterohepatic circulation re-expose from the lumenal direction; and pathway 3, exposure via blood circulation. To investigate these possible pathways, the following surgical procedures were performed: (a) portal catheterization for IQ administration to eliminate pathway 1 and (b) choledochal catheterization for bile drainage to eliminate pathway 2. When both procedures are combined, only pathway 3 is active. Four types of IQ-DNA adducts were commonly observed in the colons of all experimental groups, with no qualitative difference between the mucosal and muscular layers. When IQ-HCl was administered by p.o. gavage at a dose of 100 mumol/kg body weight, approximately 70% of the IQ DNA adducts in the colonic mucosa (13.1 +/- 4.3 adducts/10(7) nucleotides) was induced through pathway 1. Pathway 3 induced the remaining 30% of mucosal adducts, producing equal adduct levels in both layers. Pathway 2 did not work for adduct formation. The DNA adduct formation was unaffected in the presence of intestinal flora, indicating that detoxified IQ does not reactivate by floral enzymes. In conclusion, mucosa-specific DNA adduct formation in the colon is caused most likely by the absorption of carcinogens through the lumen. PMID- 7796401 TI - Initiatives with platinum- and quinazoline-based antitumor molecules--Fourteenth Bruce F. Cain Memorial Award Lecture. AB - Carboplatin is a better-tolerated alternative to cisplatin. JM216, the first p.o. administrable platinum complex possesses toxicities comparable to carboplatin in Phase I studies. Together with the trans-platinum complex JM335, it provides new chemical guidelines for the development of compounds that may circumvent cisplatin resistance in tumors. Systematic structure-activity investigations have led to the discovery and development of ZD1694 (Tomudex), an inhibitor of thymidylate synthase that exploits both the reduced folate carrier and folylpolyglutamate synthetase as major determinants of its growth-inhibitory activity. Phase II studies have revealed encouraging activity against colon cancer, and Phase III studies are nearing completion. An associated structure activity investigation has led to the development of ZD9331, a potent thymidylate synthase inhibitor which exploits the reduced folate carrier for cell entry, but which is independent of polyglutamation for its thymidylate synthase-inhibitory activity. This compound possesses antitumor activity in vivo and has been selected for full development. PMID- 7796403 TI - GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. AB - The cell surface gangliosides GM2, GD2, and GD3 are often overexpressed in malignant melanoma. We have shown previously that immunization of melanoma patients with GM2 and Bacillus Calmette-Guerin induced an IgM antibody response in most patients and that patients with high titer GM2 antibodies showed increased survival. As is commonly seen with carbohydrate antigens (which are T independent), the IgM response was short lived, and an IgG response was rarely observed. To increase immunogenicity, we conjugated GM2 covalently with keyhole limpet hemocyanin (KLH). GM2-KLH vaccine was given to melanoma patients alone or with one of the three adjuvants: Bacillus Calmette-Guerin, DETOX, or QS-21. The most effective vaccine was GM2-KLH with QS-21. It induced a much higher titer, a longer-lasting IgM GM2 antibody response, and a consistent IgG response (isotype IgG1 and IgG3). It also induced the highest titer anti-KLH response. The results suggest that the conjugate GM2-KLH plus QS-21 vaccine elicited significant T-cell help. Because there was no serious toxicity, this vaccine approach is attractive for augmenting the immunogenicity of other gangliosides, such as GD2 and GD3, and to determine the effects of ganglioside antibodies on the course of melanoma. In addition, the finding that QS-21 significantly increased the immunogenicity of GM2-KLH suggests that it may do the same for other conjugate vaccines, many of which are currently used without adjuvant. PMID- 7796404 TI - Glutathione S-transferase activity and glutathione S-transferase mu expression in subjects with risk for colorectal cancer. AB - The glutathione S-transferases (alpha, mu, and pi), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-mu expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer. Total GST activity was determined spectrophotometrically with the use of 1-chloro-2,4-dinitrobenzene as a substrate. The ability to express the um subclass of GST was determined with the use of an ELISA. Although interindividual variability in the GST activity of blood lymphocytes was greater than 8-fold (range, 16.7-146.8 nmol/min/mg), the GST activity of blood lymphocytes and colon tissue within an individual was constant over time and was unrelated to sex, age, or race. The GST activity of blood lymphocytes from high-risk individuals was significantly lower than that of blood lymphocytes from control individuals (P < or = 0.004). No association was observed between the frequency of GST-mu phenotype and risk for colorectal cancer. Blood lymphocytes from high-risk individuals unable to express GST-mu had lower levels of GST activity than did those from control subjects with the GST-mu null phenotype; however, this difference was significant in male subjects only (P < or = 0.006). Analysis of paired samples of blood lymphocytes and colon tissue indicated a strong correlation between the GST activity of the two tissue types (Spearman's rank correlation, r = 0.87; P < or = 0.0001). The GST activity of blood lymphocytes may be used to identify high-risk individuals with decreased protection from this Phase II detoxication enzyme who may benefit from clinical trials evaluating GST modulators as chemopreventive agents for colorectal cancer. The GST activity of blood lymphocytes may also be used in colorectal cancer chemoprevention trials to monitor the responsiveness of colon tissue to regimens that modify Phase II detoxication enzymes. PMID- 7796405 TI - Tyrphostin AG17, [(3,5-Di-tert-butyl-4-hydroxybenzylidene)- malononitrile], inhibits cell growth by disrupting mitochondria. AB - [(3,5-Di-tert-butyl-4-hydroxybenzylidene)-malononitrile] (AG17), a "tyrphostin" tyrosine kinase antagonist, was found to inhibit tumor cell growth with 50% growth inhibition ranging from 0.7 to 4.0 microM in a panel of 13 human tumor cell lines, as evaluated by tetrazolium dye reduction and inhibition of precursor incorporation into macromolecules. The promyelocytic leukemia cell line HL 60(TB), was the most sensitive with irreversible total growth inhibition after 12 h of exposure to 1.5 microM drug. Antiproliferative effects of AG17 in HL-60(TB) cells were temporally related to disruption of mitochondrial function, which occurred within 1 h after drug exposure as demonstrated by a significantly decreased mass of ATP in drug-treated cells, loss of the fluorescent mitochondrial membrane potential probe rhodamine 123, and ultrastructural examination of mitochondria using fluorescence and electron microscopy. Specific decreases of total or tyrosine-phosphorylated substrate at concentrations of the drug not affecting ATP levels were not detected. These data raise the possibility that AG17 may act in part by altering mitochondrial function and/or structure, and that impairment of mitochondrial function may be exploitable as a potentially useful mechanism to modulate tumor cell proliferation. This study also emphasizes the importance of evaluating carefully the effects of potential protein kinase antagonists, since these structures have effects in intact cells in addition to what might be expected from in vitro enzyme assays. PMID- 7796406 TI - The interaction of hydroxyurea and iododeoxyuridine on the radiosensitivity of human bladder cancer cells. AB - Biochemical modulation of iododeoxyuridine (IdUrd) incorporation into the DNA of tumor cells is a potential clinical strategy to enhance radiosensitivity and to simultaneously differentiate the sensitivity of rapidly proliferating tumor cells and more slowly proliferating adjacent normal tissues to radiation. The interactions of hydroxyurea (HU) and IdUrd were studied in a human bladder cancer cell line, 647V. Exposure of exponentially growing 647V cells to HU concentrations of 10-100 microM for one cell population doubling (24 h) resulted in no cytotoxicity as assessed by clonogenic survival. Flow cytometric analysis showed a significant increase in an early S-phase population after a 12-h exposure but a return to a normal cell cycle distribution after a 24-h exposure to 100 microM HU. Incorporation of IdUrd into DNA was increased 2-fold by coincubation with HU (100 microM) and a clinically achievable concentration of IdUrd (2 microM) for 24 h. To elucidate the mechanism of modulation, IdUTP pools were compared in 647V cells treated with 2 microM IdUrd with or without 100 microM HU. A 2-fold increase in IdUTP pools was evident within 2 h when this drug combination was used. With the use of multivariate statistical analysis, the radiosensitivity of 647V cells was compared after a 24-h exposure to various concentrations of IdUrd (0 and 2 microM) and HU (0, 10, and 100 microM). A 24-h exposure to 100 microM HU alone or to 2 microM IdUrd alone before irradiation resulted in significant (P < 0.02) radiosensitization with sensitizer enhancement ratios of 1.15 and 1.27, respectively. A 24-h exposure to 100 microM HU + 2 microM IdUrd resulted in even more significant (P = 0.001) radiosensitization, which was found to be a greater than additive response (sensitizer enhancement ratio, 1.76 observed compared with 1.37 expected). No radiosensitization was found with a 12-h exposure to 100 microM HU alone. The mechanism of biochemical modulation of IdUrd by a noncytotoxic dose of HU is proposed as increasing the IdUTP pools by stimulating enzymes in the thymidine salvage pathway and subsequently enhancing IdUrd incorporation and radiosensitization. PMID- 7796407 TI - Antitumor activities of a new indolocarbazole substance, NB-506, and establishment of NB-506-resistant cell lines, SBC-3/NB. AB - The novel anticancer glucosyl derivative of indolo-carbazole (NB-506), an inhibitor of DNA topoisomerase I, exhibited strong in vitro cytotoxicity against various human cancer cell lines. In order to elucidate its cytotoxic mechanisms, we established nine NB-506-resistant sublines with different resistance ratios from human small cell lung cancer cells (SBC-3/P) by stepwise and brief exposure (24 h) to NB-506. Among them, SBC-3/NB#9 was 454 times more resistant to NB-506 than the parent cell line. The SBC-3/NB#9 cells showed cross-resistance only to topoisomerase I inhibitors, such as 11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecia and 7-ethyl-10-hydroxy-camptothecin, and not to other anticancer drugs, such as vincristine, vinblastine, Adriamycin, etoposide, and teniposide. These results indicate that the difference on the effect of topoisomerase I was considered to be related to a resistance mechanism. The topoisomerase I activities of nuclear extracts eluted from SBC-3/NB#9 cells was only one-tenth of the parent cell activity. A Western blotting study indicated that this lower activity was due to a lower amount of DNA topoisomerase I. Furthermore, we found correlations between topoisomerase I activity and sensitivity to NB-506 in sublines with different degrees of resistance. Accumulation of 3H-labeled NB-506 by SBC-3/NB#9 cells was only one-fifth of that by the parent cells, whereas intracellular accumulation of 3H-labeled camptothecin by both cell lines did not differ. The reduction of accumulation was specific to NB-506, and this result may explain why the resistance ratio for NB 506 was higher than those for 11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-hydroxy-camptothecin. PMID- 7796408 TI - Mechanism of action of the antineoplastic drug lonidamine: 31P and 13C nuclear magnetic resonance studies. AB - The mechanism of action of the antineoplastic drug lonidamine (LND) on MCF-7 human breast cancer cells was studied with the use of 31P and 13C nuclear magnetic resonance (NMR) spectroscopy. The cells were embedded in alginate microcapsules, perfused with growth media and LND at physiological conditions in the NMR tube, and continuously monitored in vivo for the effects of LND. 31P NMR demonstrated intracellular acidification after LND perfusion concomitant with ATP depletion and changes in phospholipid metabolites. 13C NMR showed marked LND induced accumulation of lactate, and spectra of the perfusate disclosed that LND inhibited lactate transport. Kinetic 13C NMR also furnished information on LND effects on glucose metabolism; LND decreased initial glucose uptake and lactate formation, although the final intracellular glucose levels were higher compared with those in controls. Combined administration of LND and the metabolic inhibitor 2-deoxyglucose yielded additive but not synergistic cytotoxicity and enabled assessment of hexokinase activity. Overall, the results indicate that the major metabolic changes induced by LND are inhibition of lactate transport and its accumulation, which lead to intracellular acidification. PMID- 7796410 TI - Application of a tumor suppressor (C-CAM1)-expressing recombinant adenovirus in androgen-independent human prostate cancer therapy: a preclinical study. AB - Recently, we demonstrated that an androgen-regulated cell adhesion molecule, C CAM, acts as a tumor suppressor in prostate cancer development. In this study, we further explored the possibility of applying C-CAM as a potential agent for developing prostate cancer gene therapy using an adenoviral delivery system. We found that prostate cancer cells, in general, were sensitive to adenoviral infection. In vitro characterization indicated that C-CAM1 protein was detected only in C-CAM1 adenovirus-infected cells but not in antisense control virus infected cells, and the levels of expression showed dose dependency. Because of the stability of the protein, C-CAM expression in viral-infected cells appeared to be a long-lasting event, indicating that C-CAM may be superior to many other known tumor suppressors that have a short protein half-life. Most importantly, the delivery of a single dose of C-CAM adenovirus was able to repress the growth of PC-3-induced tumors in nude mice for at least 3 weeks. Taken together, these data indicate that C-CAM is a potential candidate for human prostate cancer therapy. PMID- 7796409 TI - 20-epi-vitamin D3 analogues: a novel class of potent inhibitors of proliferation and inducers of differentiation of human breast cancer cell lines. AB - We have studied the in vitro biological activities and mechanism of action of 1,25-dihydroxyvitamin D3 (1,25D3) and four potent 1,25D3 analogues [20-epi-22oxa 24a,26a,27a-tri-homo-1,25(OH)2D3 (KH 1060); 20-epi-1,25(OH)2D3; 1,25(OH)2-16ene D3; and 1,25(OH)2-16ene-23yne-D3] on proliferation and differentiation of estrogen receptor-negative (MDA-MB-436, BT-20, SK-BR-3, and MDA-MB-231), estrogen receptor-weakly positive (BT474), and estrogen receptor-positive (MCF-7) breast cancer cell lines. Dose-response studies showed that KH 1060 was the most potent analogue, because it was able to induce differentiation in all seven breast cancer cell lines (measured by lipid staining) and to suppress more than 50% clonal proliferation (ED50) at 10(-10) M in all cell lines, except MDA-MB-436 and BT-20. To explore how these compounds mediated antiproliferative actions, their effects on the cell cycle, on expression of bcl-2 and p53, and on apoptosis were assessed. Five of six cell lines have a mutant p53 gene, whereas MCF-7 has wild type p53. Immunohistochemical staining showed that the p53 protein was predominantly localized in the nucleus in each of the breast cancer cell lines except for MCF-7, which expressed the protein predominantly in the cytoplasm. After incubation with KH 1060 (3 days; 10(-7) M), expression of bcl-2 protein as determined by immunohistochemical localization was markedly decreased in BT-474, MCF-7, and MDA-MB-231; these same cells were profoundly inhibited in their clonal proliferation and arrested in the G0/G1 phase of the cell cycle when cultured with KH 1060. In contrast, BT-20 and MDA-MB-436 cells that were refractory to the antiproliferative effect of KH 1060 (ED50 < 10(-6) M) had no down-regulation of their bcl-2 expression and no cell cycle changes after exposure to KH 1060. MCF-7 showed morphological changes and DNA fragmentation, indicative of apoptosis after 48 h incubation with KH 1060 (10(-6) M), during which time p53 protein accumulated in the nucleus and decreased in the cytoplasm. In contrast, no apoptosis was detected in three other breast lines (MDA-MB-231, SK-BR-3, and BT 474) that had a mutated p53. In conclusion, the data indicate that KH 1060 is an extremely potent 1,25D3 analogue inducing differentiation of all six breast cancer lines and potently inhibiting clonal growth of four of them with concomitant decreased bcl-2 and cell cycle arrest at G0/G1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7796411 TI - Effect of the chemoprotective agent WR-2721 on disposition and biotransformations of ormaplatin in the Fischer 344 rat bearing a fibrosarcoma. AB - The effects of the phosphorothioate agent, WR-2721, have been investigated with respect to the biotransformations of ormaplatin in the Fischer 344 rat bearing a transplanted fibrosarcoma. A number of different paradigms of dosing route and schedule for the administration of the two agents have been investigated. In the first group of experiments, WR-2721 (200 mg/kg, i.p.) was administered 30 min before ormaplatin (12.5 mg/kg, i.p.), and then peritoneal fluid, plasma, and tissues were harvested at 30 min after the ormaplatin administration. Our results suggest that a significant interaction between WR-2721 and ormaplatin is occurring in the peritoneal cavity. The interaction was evident in terms of both effects on distribution and disposition of total platinum and in alterations of the profiles of biotransformation products formed in the various tissues and fluids. Plasma protein binding of ormaplatin was decreased by 50% in the presence of WR-2721. Total platinum in the spleen was decreased by 66% and in the liver by 50%. There were no trends among the findings that would indicate any selectivity between tumor and nontumor tissue with respect to the effects of WR-2721 on the parameters measured. Subsequent investigations examined the effects of dosing the WR-2721 by the i.v. route while continuing with the i.p. administration of the ormaplatin. WR-2721 was administered either 30 or 5 min before the ormaplatin, and the plasma and tissues were harvested at 15, 30, or 60 min after ormaplatin administration. The reverse-phase HPLC peak, which behaved chromatographically as a Pt(dach)(WR-1065) standard, was less prominent after the i.v. administration of WR-2721 than it was after i.p. administration under any of the paradigms tested. There was again no evidence for selectivity between tumor and nontumor tissue in the findings from any of the paradigms. It is concluded that if WR-2721 is capable of selectively protecting nontumor tissue from the toxicities of platinum based chemotherapy, it is doing so by some mechanism other than its selective uptake into normal tissue and subsequent nonspecific inactivation of any reactive cytosolic platinum species formed. Other possible mechanisms are briefly discussed. PMID- 7796412 TI - Activity of temozolomide in the treatment of central nervous system tumor xenografts. AB - The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin- 4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice bearing s.c. and intracranial tumors. Temozolomide administered daily for a total of five doses demonstrated marked activity against a panel of Mer+ xenografts despite marginal to moderate activity of 1,3-bis(2-chloroethyl)-1 nitrosourea. The growth delays produced by temozolomide in these xenografts were 1.8-7.5-fold greater than those produced by procarbazine. Although temozolomide demonstrated marginal activity against the Mer+ cell line D341 Med when a 5-day schedule was used, a high-dose 1-day schedule resulted in moderate activity. Temozolomide produced increases in median survival of 1285% (adult glioma D-54 MG), 323% (childhood glioma D-456 MG), and 68% (ependymoma D612 EP). Pretreatment of mice with O6-benzylguanine increased temozolomide-induced mortality, requiring reduction of the dosage from 1200 to 750 mg/m2 on the single-day regimen. O6 Benzylguanine pretreatment of mice bearing Mer+ D341 Med increased the growth delay of temozolomide, in duplicate experiments, from -3.1 to 4.8 and 1.1 to 4.9 days. These studies suggest that temozolomide may be active in the treatment of a broad spectrum of central nervous system cancers, including Mer+ tumors resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea. PMID- 7796413 TI - Improved tumor radioimmunodetection using a single-chain Fv and gamma-interferon: potential clinical applications for radioimmunoguided surgery and gamma scanning. AB - Previous studies have shown that (a) single-chain antibody binding proteins, or sFvs, localize experimental tumor xenografts (D.E. Milenic et al, Cancer Res., 51: 6363-6371, 1991) and (b) the administration of gamma-interferon (IFN-gamma) increases the expression of a high molecular weight glycoprotein, tumor associated glycoprotein 72 (TAG-72), which improves mAb-based tumor targeting as well as radioimmunotherapy (J. W. Greiner et al., Cancer Res., 53: 600-608, 1993). The present experimental study was designed to determine whether exploiting those two observations in combination could augment tumor detection. Initial results revealed significant localization of a single-chain antibody binding protein of CC49 (i.e., CC49 sFv), a second generation anti-TAG-72 mAb, to human colon tumor xenografts (HT-29), which express low constitutive TAG-72 levels. IFN-gamma treatment of mice bearing HT-29 tumors significantly increased TAG-72 levels in the tumor xenografts. Increased TAG-72 expression was accompanied by a 2-4-fold augmentation of CC49 sFv localized to the HT-29 tumors, measured by direct quantitation of 125I-labeled CC49 sFv tumor deposition as well as tumor:normal tissue ratios. Enhanced CC49 sFv tumor localization improved HT 29 tumor visualization by external scintigraphy as well as when using a hand-held gamma-detecting probe to discriminate between normal (i.e., heart, hind leg) and tumor tissue. The gamma-detecting probe was the same as that used intraoperatively with 125I-labeled CC49 IgG to identify occult tumors in patients. The present experimental findings indicate that the efficiency by which 125I-labeled CC49 sFv localizes tumor in vivo can be enhanced with IFN-gamma. Results of the present study suggest that (a) the incorporation of an IFN-gamma treatment schema prior to radioimmunscintigraphy may increase the signal from the tumor site(s), thus providing a better discrimination between tumor and background, and (b) combining 125I-labeled CC49 sFv with IFN-gamma will not only reduce the time interval between antibody injection and surgery, but will also increase the efficiency of tumor localization using the intraoperative gamma detecting probe. PMID- 7796414 TI - Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers. AB - We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers. PMID- 7796415 TI - Loss of heterozygosity of tumor suppressor genes in testis cancer. AB - Little is known of the molecular changes that occur in germ cell tumors (GCT) of the testis. We studied three GCT cell lines and 44 tumors for loss of heterozygosity (LOH) of the tumor suppressor genes APC, MCC, DCC, RB, TP53, and WT-1. We observed that LOH occurred in 55% (21 of 38) of informative cases at DCC, in 28% (10 of 36) of informative cases at APC, in 23% (6 of 26) at MCC, in 30% (13 of 43) at RB, and in 27% (6 of 22) at WT-1. The LOH level in these tumors using anonymous primers mapping to the short and long arms of chromosome 19, which is cytogenetically normal in GCT, revealed LOH of 11 and 5%, respectively. We also observed a LOH of 22% in the TP53 gene, despite the fact that mutations in TP53 do not occur in testis cancer. Since a high frequency of LOH at DCC (18q21.3) occurs equally at all histological subsets in GCT, we conclude that the loss of the function of this gene is an early event in testicular GCTs. However, the observed LOH levels at APC/MCC (5q21), RB (13q14), and WT-1 (11p13) could represent a functional loss of the corresponding tumor suppressor gene in some GCTs or reflect the loss of sequences in the same general chromosome region but involving a different tumor suppressor locus. Therefore, detailed mapping of these chromosomes is required to define the precise locations of maximal LOH in testis cancer. PMID- 7796416 TI - Frequent detection of bcl-2/JH translocations in human blood and organ samples by a quantitative polymerase chain reaction assay. AB - Using an ultrasensitive assay involving the PCR, we have examined the frequency of a follicular lymphoma-associated translocation in peripheral blood from 132 individuals, most of whom were healthy blood donors. This translocation occurs between the bcl-2 proto-oncogene and the JH gene region and prolongs the life of lymphocytes. At a level of sensitivity of 1 translocation-bearing cell per 5 x 10(6) cells, almost one-half of healthy human adults had this translocation in the mononuclear fraction of peripheral blood. However, the range of frequency of these translocations spanned almost three orders of magnitude among translocation positive individuals. Furthermore, there was a statistically significant increase with age in the percentage of individuals who were translocation positive. Such an age correlation was also seen for the percentage of blood donors with rather high translocation frequencies (> or = 20 per 5 x 10(6) peripheral blood mononuclear cells). However, the blood donor who had by far the highest concentration of this translocation was a healthy 35-year-old male containing approximately 900 apparently monoclonal, translocation-bearing cells per 5 x 10(6) peripheral blood mononuclear cells. Our findings suggest that some individuals who may be at risk for follicular lymphoma might be able to be identified by this PCR assay on peripheral blood. Also, these data may help explain the age dependence of the occurrence of this cancer. PMID- 7796417 TI - Chromosome 9p allelic loss and p16/CDKN2 in breast cancer and evidence of p16 inactivation in immortal breast epithelial cells. AB - To define the extent of involvement of chromosome 9p in breast carcinogenesis, we performed microsatellite length polymorphism analysis of markers spanning this region. Of 24 primary breast carcinomas analyzed, we observed a high frequency (58%) of loss of heterozygosity or allelic imbalance affecting subregion 9p21-22. Mutational analysis of CDKN2 (p16) was performed to determine whether this gene was the target of such alterations. Of 21 tumors analyzed, only 1 showed a mutation of probable consequence, suggesting that CDKN2 appears not to be the target of loss of heterozygosity and indicating the possible existence of another tumor suppressor gene within this region. Additionally, since it has been suggested that some CDKN2 deletions and mutations could be due to an in vitro phenomenon, four immortal breast cell lines derived from normal epithelium, MCF10F, MCF12F, 184A1, and 184B5, were examined for loss or mutation of CDKN2. Two lines (MCF10F and MCF12F) showed homozygous deletions of CDKN2, and one (184A1) revealed a hemizygous deletion and a nonsense mutation in the remaining allele. This could imply an important role of CDKN2 in the control of immortalization or in vitro adaptation and is the first evidence of such in nontumor-derived cell lines. Additionally, this is the first report of frequent loss of heterozygosity in the 9p21-22 chromosome subregion of uncultured primary breast tumors. PMID- 7796418 TI - A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence. AB - We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB 2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems. PMID- 7796419 TI - Seven megabase yeast artificial chromosome contig at region 11p15: identification of a yeast artificial chromosome spanning the breakpoint of a chromosomal translocation found in a case of Beckwith-Wiedemann syndrome. AB - Genetic alterations of chromosome region 11p15 have been detected in neoplastic diseases as well as in cancer-predisposing syndromes. The cloning of the entire chromosomal region will be important for the identification and characterization of critical tumor suppressor genes. We have developed a yeast artificial chromosome contig that covers up to 7 Mb of this chromosome band. The most centromeric marker included in the contig is D11S932 and the most telomeric is D11S470. We have developed 18 new STS markers, which have been located in the contig in relation to 16 known markers. One of the yeast artificial chromosome clones was found to span the chromosome 11 breakpoint of the translocation t(11;18), associated with a case of Beckwith-Wiedemann syndrome. Cloning the regions in proximity to this translocation might reveal the presence of a gene altered in association with the development of Beckwith-Wiedemann syndrome. PMID- 7796422 TI - Symposium on advanced treatment options for the failing left ventricle. New Haven, Connecticut, June 10-11, 1994. PMID- 7796421 TI - Cyclic AMP-regulated synthesis of the tissue inhibitors of metalloproteinases suppresses the invasive potential of the human fibrosarcoma cell line HT1080. AB - Tissue inhibitors of metalloproteinases (TIMPs) play an important role in regulating the activity of matrix metalloproteinases (MMPs). Tumor cell invasion and metastasis closely correlate with the activities of two members of MMPs, MMP2 and MMP9, both of which degrade type IV collagen in basement membranes. We herein report that the treatment of HT1080 cells with 8-bromo-cAMP and other chemicals that activate cyclic adenylase activity induces the expression of TIMP1 and TIMP2 both at the mRNA and the protein levels and that this induction of TIMPs correlates with suppression of invasive phenotypes of HT1080 cells. Treatment with various cAMP-elevating reagents induced the expression of TIMPs and MMP2 in HT1080 cells, whereas the expression of MMP9 was not significantly affected. The protein amounts of TIMP1, TIMP2, and MMP2 secreted into the medium from HT1080 cells treated with 1 mM 8-bromo-cAMP were 7.9-, 9.3-, and 8.5-fold higher than those secreted from untreated cells, respectively. Induction of these mRNAs by 8 bromo-cAMP was blocked by HA1004, a protein kinase A inhibitor, but not by calphostin C, a protein kinase C inhibitor. Cycloheximide abolished the induction of TIMPs and MMP2 mRNAs by 8-bromo-cAMP, indicating that the induction depends on a newly synthesized protein(s) whose expression may be regulated by cAMP. Type IV collagenolytic activity and the invasiveness of HT1080 cells, both of which were suppressed by 8-bromo-cAMP, were efficiently restored when the cells were exposed to anti-TIMP antibodies, demonstrating the importance of the increased levels of TIMP1 and TIMP2 proteins for the cAMP-mediated suppression of both type IV collagenolytic activity and the invasiveness of HT1080 cells. PMID- 7796420 TI - Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. AB - The p53-regulated gene product p21WAF1/CIP1 is the prototype of a family of small proteins that negatively regulate the cell cycle. To learn more about p21WAF1/CIP1 regulation in vivo, monoclonal antibodies were developed for immunohistochemistry. These revealed that p21WAF1/CIP1 expression followed radiation-induced DNA damage in human skin in a pattern consistent with its regulation by p53. A detailed comparison of the human, rat, and mouse p21WAF1/CIP1 promoter sequences revealed that this induction was probably mediated by conserved p53-binding sites upstream of the transcription start site. In unirradiated tissues, p21WAF1/CIP1 expression was apparently independent of p53 and was observed in a variety of cell types. Moreover, there was a striking compartmentalization of p21WAF1/CIP1 expression throughout the gastrointestinal tract that correlated with proliferation rather than differentiation. As epithelial cells migrated up the crypts, the Ki67-expressing proliferating compartment near the crypt base ended abruptly, with the coincident appearance of a nonproliferating compartment expressing p21WAF1/CIP1. In colonic neoplasms, this distinct compartmentalization was largely abrogated. Cell cycle inhibitors are thus subject to precise topological control, and escape from this regulation may be a critical feature of neoplastic transformation. PMID- 7796423 TI - Advanced treatment options for the failing left ventricle. Introduction. PMID- 7796424 TI - New frontiers in heart transplantation. Clinical applications of basic research and new surgical approaches. AB - The growing understanding of alloimmune responses may help elucidate the mechanisms a novel immunomodulatory strategies, affording insights into new single or combination regimens. These insights are currently elusive because of the number of immuno-suppressive agents and techniques, the array of possible organ transplants, and the variety of experimental in vitro and in vivo models in diverse species. These possibilities add a bewildering level of complexity to the usual therapeutic problems of selecting drug doses, vehicles, routes, and schedules of administration. Although the results of in vitro assays have been used as indices of alloreactivity, they show only inconsistent correlations with clinical events. Only stringently controlled in vivo studies in rodents, large animals models, and humans will determine which agents or procedures represent real improvements over conventional therapy. The results of preclinical transplantation models and initial clinical trials suggest that immunosuppression for transplant patients is likely to evolve into various combination regimens. It appears now that there will be a choice between cyclosporine and FK506 as baseline immunosuppression because clinical experience has shown that these two drugs cause excessive nephrotoxicity when used in combination. Ideally the combination of additional new agents will enable the doses of cyclosporine and FK506 to be lowered to levels that are nonnephrotoxic and at the same time minimize or completely eliminate the need for corticosteroids and anti-T cell antibody therapy. The diverse mechanisms of immunosuppressive action of the new drugs under investigation certainly offer the hope for creative and effective strategies for the control of many forms of graft rejection in the near future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796425 TI - Permanent mechanical replacement of the left ventricle. AB - Patients with congestive heart failure have a poor prognosis and their care is expensive. Treatment with the HeartMate left ventricular assist device (Thermo Cardiosystems Inc, Woburn, MA) has indicated that life for such patients can be prolonged, quality of life increased, and cost of care decreased. Although currently approved only as a bridge to transplantation, the HeartMate and other such devices may one day offer permanent support of the left ventricle as an alternative to cardiac transplantation. PMID- 7796426 TI - Dynamic cardiomyoplasty. AB - Dynamic cardiomyoplasty is a promising new technique that appears to effect symptomatic improvement in patients with NYHA class III heart failure. Objective improvement in systolic performance of the left ventricle appears small but remains to be further defined. No survival advantage has yet been realized, although this may be seen as the technique is further refined and operative risk curtailed. Mechanism of action may include a girdling effect that prevents progressive left ventricular dilatation. This effect may be independent of any role in augmenting systolic performance. Randomized clinical trials currently in progress will provide definitive answers within the next few years to these important questions. PMID- 7796427 TI - Skeletal muscle for cardiac assist. AB - Although current efforts at cardiomyoplasty have not produced the anticipated clear-cut benefits in cardiac function, replicable improvements in subjective function have resulted. Efforts at optimizing conditioning protocols, skeletal muscle strength, and timing of skeletal muscle assist devices should provide further improvements in cardiomyoplasty. Further work with alternative ways of configuring skeletal muscle for cardiac assist is extremely promising. SMVs, in particular, offer potential to augment cardiac function directly or indirectly powering pumps. Work in all these areas is in early stages, but the future is bright. PMID- 7796428 TI - Symposium on advanced treatment options for the failing left ventricle. Synthesis. Guidelines for selection among treatment options. PMID- 7796429 TI - New medical therapies for advanced left ventricular dysfunction. AB - The analysis of currently used therapeutic targets provides considerable input in the choice of current and future therapies for dilated cardiomyopathy and congestive heart failure. Of the ion flux agents, a definitive answer concerning digoxin will soon be available. Currently, digoxin is likely of benefit to patients with persistent heart failure and significantly enlarged hearts despite therapy with preload and afterload reducing agents. Most currently available calcium channel blocking agents do not appear to be effective, although newer agents such as amlodipine and felodipine have yet to be adequately tested. Vesnarinone, which operates through the sodium and potassium rectifying channels and has limited phosphodiesterase inhibition, appears to provide a significant improvement in mortality and in symptoms. Part of the latter effect may be due to its anticytokine properties, which are currently being investigated. Analysis of vascular endothelial agents indicate that not all of the vasoactive agents improve survival, as demonstrated with prazosin and flosequinan. The dose of agents may be important, again demonstrating that less is better. Finally, those with additional effects, such as inositol triphosphate stimulation, may offer additional unique properties that may, in the future, provide benefit. Phosphodiesterase inhibitors are potentially beneficial in the short term but clearly should be avoided for long-term use. Lower doses of these agents are now being investigated, but the weight of evidence is against agents that operate primarily through phosphodiesterase inhibition. Renin angiotensin agents are the most efficacious of therapies available at this time. New angiotensin converting enzyme inhibitors are likely to add little to what is already known.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796430 TI - CABG in advanced left ventricular dysfunction. AB - Concurrent, independent clinical series at Yale University and the University of Virginia demonstrate an important role for CABG in patients with advanced ischemic cardiomyopathy. It is found that CABG can be performed safely in these patients, both angina and congestive heart failure states improve, ejection fraction increases substantially, and good long-term longevity is achieved. Despite prior concerns, the internal mammary conduit can be used safely in these patients. It appears that CABG serves to protect viable noninfarcted muscle and to recruit hibernating ischemic muscle. CABG is suggested as an alternative to heart transplantation in this patient group. PMID- 7796432 TI - Medical therapy and prognosis in chronic heart failure. Lessons from clinical trials. AB - The past two decades have witnessed tremendous advances in the pharmacologic therapy of patients with left ventricular dysfunction and chronic heart failure. The pharmacologic repertoire has been and continues to be expanded with newer agents carefully subjected to the rigor of well-designed clinical trials. Treatment has consequently evolved from pathophysiologically guided therapy predicated on older concepts to evidence-guided therapy supported by results of major clinical trials that continue to expand the understanding of the pathophysiology of this complex syndrome. The goals of therapy have ambitiously evolved from the immediate symptomatic relief offered by diuretics; to the short term hemodynamic improvement in the circulation produced by direct vasodilators; to the intermediate-term improvement in functional capacity and exercise tolerance associated with vasodilators, nitrates, and digoxin; and to the final frontier of long-term improvement in morbidity and survival associated with ACE inhibitor therapy. In addition to the expansion of the understanding of the epidemiology, natural history, and pathophysiology of chronic heart failure, several important lessons in clinical pharmacology have been learned from the clinical trials of the last decade. Many other questions, however, remain unanswered. The role of diuretics, although uncontested in the acute stabilization of congested patients, has yet to be rigorously evaluated in stable patients with chronic left ventricular dysfunction on ACE inhibitors. The long term effects of nitrates on morbidity and mortality have not yet been established in patients with either ischemic or nonischemic ventricular dysfunction. Vasodilators as a class, and perhaps because they are not a homogeneous class, have had a mixture of successes and failures. There is no evidence that pure vasodilation in and by itself improves survival. There is ample evidence, however, that it improves the circulation and consequently the response to diuretics. This improvement may translate into intermediate-term improvement in functional capacity, but this benefit is seldom sustained. Hemodynamic improvement in the circulation may not always translate into longer-term improvement in morbidity and reduction in mortality. The syndrome of chronic heart failure from systolic left ventricular dysfunction has emerged as a disease of mechanical dysfunction and maladaptation. The maladaptation is a consequence of deleterious effects of compensatory neurohormonal mechanisms: the sympathetic nervous system, renin-angiotensin-aldosterone system, arginine vasopressin, and most likely a host of other mechanisms. The degree of activation of these mechanisms has been established as a marker of prognosis, and the effects of pharmacologic agents on these mechanisms may well determine their long-term effect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7796431 TI - Nuclear imaging techniques for the assessment of myocardial viability. AB - Regional and global left ventricular dysfunction caused by coronary artery disease may be reversible in a significant proportion of cases. This fact has important clinical implications. Apart from symptoms of angina and angiographic severity of coronary artery disease, potential for an improvement in left ventricular dysfunction should be taken into account when considering revascularization for the management of patients with coronary artery disease. Because left ventricular function is an important determinant of long-term prognosis in patients with coronary artery disease, identification and appropriate treatment of reversible left ventricular dysfunction may improve prognosis in many patients with significant left ventricular dysfunction. Table 1 describes the impact of myocardial viability in relation to the clinical objectives in various groups of patients with coronary artery disease. The choice of the optimal technique for the detection of myocardial viability is a matter of ongoing debate. There is no consensus in the literature for an optimal investigative approach to predict an improvement in left ventricular function following revascularization. Most of the studies in this field are based on small numbers of patients. Further studies in larger patient populations are needed. This debate is further complicated by the fact that none of the available technologies provides a quantitative estimate of viable myocardium or the extent of improvement that can be expected following revascularization. Currently the choice of technique depends on the clinical question to be answered, the local availability of the technique, and local expertise. Obviously, cost considerations may also play an important role in choice of technique. In patients with chronic stable coronary artery disease in whom reversibility of stress-induced perfusion abnormalities is the question, stress-redistribution rest Tl-201 imaging may be the preferred modality. In patients with congestive heart failure, in whom reversibility of left ventricular function is the issue, PET imaging or rest Tl-201 imaging may provide the appropriate answer. In post infarction patients, choice of test may depend on whether detection of residual ischemia or stunned myocardium is the issue. PMID- 7796433 TI - Left ventricular aneurysmectomy in advanced left ventricular dysfunction. AB - Despite widespread application in clinical practice and extensive laboratory investigations, many basic issues regarding left ventricular aneurysmectomy remain to be resolved. Analysis of clinical data from the authors' three centers and application of powerful modern imaging techniques provide important information to resolve these issues. PMID- 7796434 TI - Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction. AB - Patients with aortic regurgitation and severe left ventricular dysfunction remain candidates for aortic valve replacement, as long as the risks of late left ventricular dysfunction and congestive heart failure have been fully discussed with the patient, the patient's family, and the referring physician. In contrast, patients with mitral regurgitation and severe systolic dysfunction are at considerable risk of more severe left ventricular dysfunction after operation, especially if mitral valve repair or chordal-sparing procedure cannot be performed. In patients who are candidates for such procedures that preserve the integrity of the subvalvular mitral apparatus, operation may be successful in selected patients despite moderate-to-severe depression of systolic function. Prognosis is guarded to poor in patients with regurgitant valvular lesions and advanced left ventricular dysfunction, and the emerging alternative treatments discussed in other articles in this Cardiology Clinics deserve consideration in these patients. PMID- 7796435 TI - Ventricular arrhythmias in heart failure. AB - The management of ventricular arrhythmias in patients with heart failure continues to pose many challenges. Three principles of therapy can be identified: (1) Empiric therapy is not warranted for asymptomatic ventricular arrhythmias. (2) Therapy for asymptomatic ventricular arrhythmias must be individualized. Appropriate management of the underlying cardiac disease is critical, and careful identification of therapeutic goals is necessary. (3) Patients at high risk should be included in prospective, controlled clinical trials whenever possible. PMID- 7796436 TI - Candidate selection for heart transplantation. AB - The number of patients referred for heart transplantation continues to increase at a rate well beyond the number of available donors. Further attempts to expand the donor pool may be difficult and certainly cannot keep pace with the increased demand. Uniform criteria for candidate selection are critically needed. Significant functional impairment of cardiac origin, as demonstrated by oxygen consumption treadmill testing on maximal medical therapy, should be documented in all patients before considering definitive evaluation for heart transplant. Patients whose peak oxygen consumption is less than 50% of predicted should be seriously considered for transplantation. Similarly, those patients whose peak VO2 is greater than 60% of predicted probably do not warrant listing as transplant candidates in the absence of other significant risk factors, such as malignant ventricular arrhythmias unresponsive to drug therapy or ongoing ischemia not suitable for revascularization. Application of these fairly simple but definitive guidelines should help significantly reduce the number of patients on the transplant waiting list and allow patients with the greatest survival benefit to receive a graft in a much shorter period of time. PMID- 7796437 TI - Subcellular features of calcium signalling in heart muscle: what do we learn? PMID- 7796438 TI - Snakes and seaweed: a case of the swollen organ. PMID- 7796439 TI - Left atrial mechanical and biochemical adaptation to pacing induced heart failure. AB - OBJECTIVE: To determine the left atrial mechanical and biochemical adaptations to congestive heart failure, 10 dogs with rapid atrial and ventricular pacing and seven control dogs were studied. METHODS: Animals were instrumented with left atrial sonomicrometers and micromanometers and left atrial pressure-volume relationships were generated by phenylephrine boluses for maximum elastance (Emax) and end systolic elastance (Ees) calculations. Left atrial maximum volume, ejection fraction, and mean circumferential fibre shortening (Vcf) were compared at matched left atrial pressure. At necropsy, myosin heavy chain (MHC) isoforms from the left atrial body and appendage were separated with SDS-PAGE, stained with monoclonal antibodies to alpha and beta MHC, and quantified with laser densitometry. RESULTS: Left atrial ejection fraction and Vcf were significantly lower and maximum atrial volume and atrial systolic stroke volume were significantly greater in heart failure than in control. Emax was not significantly altered in heart failure, at 5.9(SD 2.9) v 4.5(1.6) mm Hg.ml-1 in controls. However, Vcf was lower (P < 0.05) and the A loop pressure-volume area (an index of eternal mechanical work performed by the left atrium) was greater (P < 0.05) in heart failure than in control dogs. The percent beta MHC in the left atrial body was greater in dogs with heart failure than in controls, at 42.6(9.8) v 17.3(9.0)%, P < 0.05. By contrast there was no significant beta MHC isoform switch in the left atrial appendage [14.4(7.6) v 17.9(9.7)%]. CONCLUSIONS: In this model of left atrial pressure and volume overload, there is significant upregulation of beta MHC in the left atrial body but not in the appendage and this isoform switch is associated with decreased velocity of left atrial contraction, increased atrial mechanical work, and unchanged force generation. PMID- 7796440 TI - Comparison of twitch force and calcium handling in papillary muscles from right ventricular pressure overload hypertrophy in weanling and juvenile ferrets. AB - OBJECTIVE: The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. METHODS: After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical function (that is, isometric twitch force and passive stiffness), intracellular [Ca2+] using the calcium indicator aequorin, markers of myocardial energy supply, and quantified connective tissue content were studied. RESULTS: It was previously found that there was a reduced peak isometric twitch force despite normal [Ca2+]i in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling ferrets (POHw) age 7 weeks. POHw animals showed a similar degree of hypertrophy to that found in the POHj. However, there was a greater peak twitch force in hypertrophied muscles at higher [Ca2+]o. There was no difference in peak [Ca2+]i: -3.1(SEM 0.1) v -3.1(0.3) (log fractional luminescence) at 16 mM [Ca2+]o for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2)% in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+]i in POHw, passive stiffness in papillary muscles was increased. Retrospective analysis of tissue from POHj revealed a connective tissue content of 24(6.8)% (P << 0.001). Thus the decreased peak twitch force reported in POHj might in part be due to an increase in fibrous connective tissue. In this study, lactate dehydrogenase was significantly higher (38%) in POHw animals. In contradistinction, total creatine kinase activity and total creatine content were significantly less (22%) in hearts from POHj animals, indicating differences in myocyte remodelling despite similar degrees and durations of hypertrophy. CONCLUSIONS: Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increased fibrosis, there is also molecular remodelling in the myocyte, as demonstrated by a decrease in the creatine kinase system. PMID- 7796441 TI - Effects of nicorandil and glyceryl trinitrate on infarct size, adenosine release, and neutrophil infiltration in the dog. AB - OBJECTIVE: The major aim of this study was to determine if nicorandil, a potassium channel opener nitrate, produces a reduction in myocardial infarct size at a non-hypotensive dose in dogs and to determine if this effect is the result of an increase in adenosine release or reduction in neutrophil infiltration into the ischaemic area. Glyceryl trinitrate was used for purposes of comparison. METHODS: Barbitone anaesthetised dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Nicorandil (100 microgram.kg-1 bolus followed by a 10 microgram.kg-1.min-1 infusion; NC/pre group), glyceryl trinitrate (10 microgram.kg-1 bolus followed by a 1 microgram.kg 1.min-1 infusion; GTN/pre group), or an equivalent volume of saline (control group) were given intravenously 15 min before occlusion and continued to the time of reperfusion. In two other groups, nicorandil (NC/post group) or glyceryl trinitrate (GTN/post group) were given 10 min before reperfusion and continued until the end of the experiment. To measure the release of adenosine from the ischaemic region, coronary venous blood samples were collected before occlusion, during occlusion, and at various times following reperfusion. Myocardial infarct size was determined by triphenyltetrazolium chloride and transmural myocardial blood flow by radioactive microspheres. Transmural myeloperoxidase activity, an index of neutrophil infiltration, was measured in biopsies obtained from the area at risk. RESULTS: Pretreatment with nicorandil and glyceryl trinitrate caused a marked reduction in myocardial infarct size expressed as percent of the area at risk [NC/pre group, 7.8(SEM 1.6)%; GTN/pre group, 11.9(2.3)%; control group, 31.0(5.6)%]. When nicorandil and glyceryl trinitrate were given before reperfusion, both drugs still produced a significant reduction in infarct size [NC/post group, 13.8(2.0)%; GTN/post group, 18.9(4.3)%]. Coronary venous adenosine concentrations during reperfusion were significantly lower in both nicorandil and glyceryl trinitrate pretreated groups, but not in the post-treated groups. Transmural myeloperoxidase activity was significantly lower in both nicorandil treated groups. CONCLUSIONS: Pretreatment with a non-hypotensive dose of nicorandil or glyceryl trinitrate markedly reduces myocardial infarct size and adenosine release from the ischaemic-reperfused area. These agents were also effective, but to a lesser degree, when given just before reperfusion. The cardioprotective actions of nicorandil appear to be related not only to its potassium channel opening activity but also in part to its nitrate activity. PMID- 7796442 TI - Identification of a new noradrenaline induced gene in the rat heart by differential mRNA display. AB - OBJECTIVE: Noradrenaline treatment of animals results in postnatal hypertrophy of the heart. This process requires many qualitative and quantitative changes in gene expression; however, the identities of the key regulatory genes which modulate the process are not known. The aim of this study was to investigate whether a recently developed technique, differential display, could provide a new route to the identification and characterisation of these critical genes. METHODS: The technique of differential display was modified for use on cardiac RNA samples and the expression of clones identified by this approach was characterised by northern analysis. RESULTS: Differential display was successfully adapted to the study of noradrenaline induced cardiac gene expression. A previously unsuspected gene was identified, the expression of which appears to be strongly modified during the onset of this process. CONCLUSIONS: Differential display offers the potential to identify and clone many of the genes critically important in regulation of growth of the mammalian heart. PMID- 7796444 TI - Digoxin affects potassium homeostasis during exercise in patients with heart failure. AB - OBJECTIVE: The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. METHODS: In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. RESULTS: Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P < 0.05). Following digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P < 0.05) at work rates of 69 W, 93 W, and at exhaustion, as well as during the first 3 min of recovery. Following digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P < 0.05) during exercise, and decreased by 66-75% (P < 0.05) during early recovery. Total loss of potassium from the leg increased by 138%. The effects of digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. CONCLUSIONS: Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training. PMID- 7796443 TI - Acadesine reduces myocardial infarct size by an adenosine mediated mechanism. AB - OBJECTIVE: The aim was to test the hypotheses that acadesine (1) augments endogenous interstitial fluid (ISF) adenosine during ischaemia, and (2) reduces infarct size by adenosine receptor mediated mechanisms. METHODS: To test these hypotheses, the left coronary artery of anaesthetised rabbits (n = 33) was occluded for 30 min and reperfused for 120 min. Acadesine (1 mg.kg-1.min-1 for 5 min, then 0.2 mg.kg-1.min-1) was infused intravenously beginning 30 min before coronary occlusion and ending 30 min after reperfusion. The area at risk was comparable in all groups, averaging 34.7 (SEM 2.2%) of the left ventricle. In separate studies (n = 22), estimates of ISF adenosine and adenosine metabolites were obtained by cardiac microdialysis. Although dialysate adenosine levels increased significantly in the area at risk during ischaemia in the untreated group [from 0.044(0.008) to 0.339(0.146) microM], acadesine did not significantly augment dialysate adenosine levels before or during ischaemia [preischaemia = 0.094(0.032) microM; ischaemia = 0.542(0.262) microM]. In addition, there was no significant difference in dialysate adenosine concentrations during the first 10 min of reperfusion, after which adenosine levels returned to baseline levels. A 2.5-fold large dose failed to increase interstitial fluid adenosine. However, the adenosine receptor blocker 8-p-sulphophenyltheophylline (SPT) in the presence of acadesine increased ISF adenosine fourfold. Acadesine significantly (P < 0.05) reduced infarct size [n = 8, 19.7(2.9)% of risk area] compared with the untreated group [n = 8, 29.4(1.3)%]. This infarct size reduction with acadesine was antagonised by SPT given during ischaemia-reperfusion [n = 8, 46.2(3.0)%] or only during reperfusion [n = 9, 42.7(2.6)%. CONCLUSIONS: Acadesine reduces infarct size by an adenosine mediated mechanism, but this cardioprotective action is not associated with significantly augmented interstitial fluid adenosine levels. PMID- 7796446 TI - Voltage dependent inhibition of ATP sensitive potassium channels by flecainide in guinea pig ventricular cells. AB - OBJECTIVE: The aim was to examine the effects of flecainide, a class Ic antiarrhythmic drug, on the ATP sensitive potassium channel (KATP channel) current in guinea pig ventricular cells, using the inside-out patch clamp technique. METHODS: KATP channel activities were recorded from inside-out membrane patches with 140 mM KCl solution bathing both the external and internal surfaces of the membrane (20-22 degrees C). Flecainide was added to the intracellular medium (ATP-free, pH = 7.3). RESULTS: Flecainide (1-300 microM) inhibited the outward KATP channel current evoked at the holding potential of +40 mV, in a concentration dependent manner. The flecainide concentration for half maximum inhibition of the channel activity (IC50) and Hill coefficient of the flecainide inhibition were estimated to be 17.3 microM and 1.1, respectively. However, flecainide did not affect the inwardly directed KATP channel current measured at the potential of -40 mV. When the inhibitory effects of flecainide on the outward current were examined under conditions in which pH was decreased from 7.3 (control) to 6.8, the IC50 and Hill coefficient became 27.3 microM and 1.2, respectively. Furthermore, in the presence of 0.1 mM ADP on the cytosolic side of the membrane (pH = 7.3), flecainide blocked the outward currents with the IC50 of 47.0 microM and a Hill coefficient of 0.9. After 1 min exposure of the cytoplasmic side of the membrane to trypsin (1 mg.ml-1), glibenclamide (2 microM) did not inhibit the KATP channel currents, while flecainide (30 microM) reversibly inhibited this trypsin enhanced KATP channel activity. CONCLUSIONS: Flecainide at relatively high concentrations blocks the cardiac KATP channels only when the currents are directed outward, and in a concentration dependent manner. The potency of flecainide in blocking KATP channels decreased under conditions of increased H+ or ADP concentrations on the cytosolic side of the membrane, as may occur in myocardial ischaemia or hypoxia. PMID- 7796445 TI - Regulation of calcium pump function in back inhibited vesicles by calcium-ATPase ligands. AB - OBJECTIVE: The aim was to evaluate the effect of changes in substrate-product concentrations of the overall sarcoplasmic reticular Ca(2+)-ATPase reactions on calcium pump function with an emphasis on those factors that modify back inhibition of the pump by intrareticular free calcium. METHODS: Sarcoplasmic reticular vesicles were isolated from the rabbit heart. Calcium uptake by the vesicles was measured with a calcium sensitive minielectrode and was related to ATPase activity, which was measured by the rate of inorganic phosphate (Pi) production or NADH oxidation. Back inhibition was varied by changing [oxalate]. RESULTS: At the high level of back inhibition and low calcium transport efficiency, calcium uptake by sarcoplasmic reticulum was stimulated by pH decrease, hydrophobic compounds, dimethyl sulphoxide, and ATP regeneration. These factors apparently modify either calcium binding to the low affinity binding site of Ca(2+)-ATPase or the effect derived from the binding of calcium to these sites. Under conditions where back inhibition was avoided and calcium transport efficiency was high, the same factors had a depressive effect on calcium uptake. Inorganic phosphate had a dual effect on the rate of calcium uptake supported by low [oxalate]: Pi < 2-3 mM strongly inhibited calcium uptake while further increase in [Pi] reversed this inhibition. At the lower level of back inhibition higher [Pi] was required to inhibit calcium transport. CONCLUSIONS: Changes in [H+], [ADP], and [Pi] can significantly affect calcium pump function, but the effect is dependent on the extent of back inhibition of calcium transport. Changes in the sarcoplasmic reticular Ca(2+)-ATPase environment which mimic those expected to take place at the start of reperfusion (pH increase to 7.0-7.1, high myoplasmic [Ca2+]) may have a depressive effect on the efficiency of calcium transport, provided that intrareticular free calcium is increased. Under those conditions factors able to decrease the inhibitory effect derived from the calcium binding to the low affinity binding sites are expected to improve the efficiency of calcium transport. PMID- 7796447 TI - Endothelin receptor subtypes in resistance arteries from humans and rats. AB - OBJECTIVE: Endothelins bind to different receptor subtypes identified as ETA and ETB receptors, ETA receptors are present on smooth muscle cells of blood vessels. ETB receptors seem to predominate on endothelial cells of blood vessels, but may also be present on smooth muscle in some vascular beds. The aim of this study was to investigate the distribution of ETA and ETB receptors in human and in rat resistance arteries. METHODS: Contractile responses to endothelin-1 and to the ETB agonist sarafotoxin S6c were investigated in human subcutaneous resistance arteries and in rat mesenteric resistance arteries mounted on a wire myograph. RESULTS: Contractile responses to endothelin-1 were significantly reduced by the ETA selective antagonists BQ123 or BQ610 in human resistance arteries, and were almost abolished by the antagonists in rat arteries. The ETB agonist sarafotoxin S6c induced smaller responses than endothelin-1. When responses to sarafotoxin S6c were obtained in the presence of BQ610, the relatively small contractile response remained. It was slightly enhanced if the responses were obtained in the presence of the nitric oxide synthase inhibitor L-NAME or after removal of the endothelium. CONCLUSIONS: Vasoconstrictor ETB receptors appear to be present in resistance vessels isolated from subcutaneous fat in humans and from the mesentery in rats, but their contribution to endothelin mediated constriction is small, particularly in rat resistance arteries. ETA receptors appear to be the more important endothelin receptor subtype in the human and rat resistance arteries examined. PMID- 7796448 TI - Reperfusion induced arrhythmias following ischaemia in intact rat heart: role of intracellular calcium. AB - OBJECTIVE: The aim was to test the hypothesis that reperfusion induced arrhythmias are associated with major alterations in intracellular calcium ([Ca2+]i) regulation. METHODS: Intracellular calcium, epicardial electrical potentials, and isovolumetric left ventricular pressure were simultaneously recorded in isolated perfused intact rat hearts during ischaemia (10 min) and reperfusion. [Ca2+]i was measured using the bioluminescent calcium indicator aequorin. RESULTS: Neither ventricular tachycardia nor ventricular fibrillation occurred during ischaemia. However, during the first minute of reperfusion ventricular tachycardia or fibrillation were frequently observed. Cellular calcium was altered by varying the perfusate calcium ([Ca2+]o; 0.5, 1.0, and 3.0 mmol.litre-1). 0% (0/6), 50% (5/10), 91% (10/11), respectively, of hearts showed ventricular tachycardia, ventricular fibrillation, or both upon reperfusion (P < 0.001, 0.5 v 3.0 mmol.litre-1). At all [Ca2+]o values examined, early ischaemia was associated with a rapid decrease in developed pressure and transient increase in the peak calcium transient followed by a gradual decline and subsequent increase in diastolic calcium during late ischaemia. The initiation of ventricular tachycardia/fibrillation upon reperfusion was immediately preceded by large increases in the amplitude of the calcium transient. These increases in systolic calcium were not seen in hearts in which ventricular arrhythmias did not occur. CONCLUSIONS: The association between reperfusion induced abrupt increases in peak calcium and the occurrence of ventricular tachycardia or fibrillation suggests that intracellular calcium transients may have a significant role in initiating these ventricular arrhythmias. PMID- 7796449 TI - Prevention of angiotensin II induced myocyte necrosis and coronary vascular damage by lisinopril and losartan in the rat. AB - OBJECTIVE: The aims were to determine: (1) if angiotensin converting enzyme (ACE) inhibition and angiotensin II receptor blockade can prevent angiotensin II induced coronary vascular damage; (2) if the cardioprotective properties of ACE inhibition are dose dependent; and (3) if the cardioprotective properties of ACE inhibition are independent of its ability to prevent the conversion of angiotensin I to angiotensin II. METHODS: Control rats and rats with either renovascular hypertension or continuous angiotensin II infusion (150 ng.min-1) for 14 d were subdivided into nine groups as follows: unoperated and untreated controls (n = 5); untreated renovascular hypertension (n = 8); untreated angiotensin II (n = 9); a renovascular hypertension group receiving one of the following doses of lisinopril 20 (n = 8), 2.5 (n = 4), and 0.6 (n = 6) mg.kg-1.d 1; a renovascular hypertension group receiving losartan (7.5 mg.d-1, n = 4); and an angiotensin II group receiving either the high dose of lisinopril (n = 6) or losartan (n = 4). Treatment was started one day before initiation of renovascular hypertension and angiotensin II infusion and continued throughout the study period. The number and size of necrotic areas and numbers of damaged coronary vessels were determined in sections of right and left ventricular tissue. RESULTS: Both coronary vascular injury and myocyte injury induced by angiotensin II were prevented by losartan. In renovascular hypertension, the lowest dose of lisinopril prevented vascular and attenuated myocyte damage but to a lesser degree than the higher doses. The cardioprotective ability of ACE inhibition is primarily the result of its ability to prevent the conversion of angiotensin I to angiotensin II. CONCLUSIONS: Angiotensin II related cardiomyocyte necrosis and coronary vascular damage are angiotensin type 1 receptor mediated and completely preventable with the receptor antagonist losartan. The ability of ACE inhibition to prevent this damage is dose dependent and primarily related to the degree to which the inhibitor can prevent the conversion of angiotensin I to angiotensin II. PMID- 7796450 TI - Wall stress induced arrhythmia is enhanced by low potassium and early left ventricular hypertrophy in the working rat heart. AB - OBJECTIVE: The aim was to investigate the effect of lowering external potassium on the sensitivity of the normal and hypertrophied rat heart to arrhythmias induced by increases in ventricular wall stress. METHODS: The isolated working heart model was used to compare hypertrophied hearts from the spontaneously hypertensive rat (SHR) with hearts from normotensive control rats (NCR) from the Wistar and Wistar-Kyoto strains. Young animals [131.5(SEM 0.64) days] were used to ensure uncomplicated left ventricular hypertrophy. Arrhythmias were induced by 20 s increases in ventricular wall stress. The ECG was recorded and the arrhythmic response of each heart was compared during perfusion with Tyrode solutions containing [K] 6, 4.8, 3.6, and 2.4 mM. RESULTS: Hypertrophied SHR hearts showed a significantly greater arrhythmic response than control hearts at all levels of afterload increase when perfused with [K] 3.6 and 2.4 mM (t test P < 0.05 and P < 0.01). Both the number and complexity of arrhythmias were increased in the SHR hearts; ventricular tachycardia occurred in 10/12 compared with 4/12 control hearts whereas ventricular fibrillation occurred in 5/12 hearts but in none of the control hearts. CONCLUSIONS: At higher levels of [K] the sensitivity of SHR and normal hearts to wall stress induced arrhythmias is similar. However, as [K] is lowered to 3.6 mM or below, hypertrophied hearts show a greatly enhanced response to increases in ventricular wall stress. They develop a larger number of ventricular ectopics and more complex ventricular arrhythmias when compared to normal hearts. This may be of relevance to arrhythmic sudden death in hypertensive patients in whom left ventricular hypertrophy, potassium depletion, and blood pressure lability is common. Excessive fluctuations in systolic pressure and therefore ventricular wall stress could provide a powerful arrhythmic stimulus in hypertensive patients with left ventricular hypertrophy, even before ischaemia, cardiac failure, or extensive extracellular fibrosis have developed. PMID- 7796451 TI - Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient rats. AB - OBJECTIVE: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart. METHODS: Copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were compared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms. RESULTS: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of alpha 1 and alpha 2 isoforms, and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. CONCLUSIONS: In the rat ventricular tissue, oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency. PMID- 7796452 TI - Adenosine and PAF dependent mechanisms lead to myocardial reperfusion injury by neutrophils after brief ischaemia. AB - OBJECTIVE: The aim was to establish whether polymorphonuclear neutrophils can, by themselves, elicit depression of postischaemic heart function immediately after short periods of ischaemia, and to examine the involvement of endogenous adenosine and platelet activating factor (PAF) in the observed phenomena. METHODS: Isolated buffer perfused guinea pig hearts performing pressure-volume work under standardised conditions were subjected to 15 min of global ischaemia. Constant flow reperfusion (5 ml.min-1) was carried out in the presence or absence of homologous neutrophils (approximately 2000 cells.microliters-1 perfusate). After 15 min of reflow, work was resumed and functional recovery assessed another 20 min later. RESULTS: In hearts perfused only with Krebs-Henseleit buffer, postischaemic heart function recovered to 67(SEM 3)% (n = 13) of the preischaemic value. As early as the first minute of reperfusion, the application of neutrophils already led to a significant decrease in recovery to 39(3)% (n = 12; P < 0.05). Without ischaemia, neutrophils did not have any deleterious effect, recovery of external heart work amounting to 91(4)% (n = 6). Adenosine concentrations measured in the coronary effluent after ischaemia were substantially increased during reperfusion from preischaemic values of < 20 nM to about 800 nM. The adenosine A1 receptor antagonist dipropyl-8-cyclopentyl xanthine prevented the neutrophil dependent loss of heart function, as did application of the PAF receptor antagonist WEB 2086, recoveries being 60(4)% (n = 6) and 58(8)% (n = 6), respectively. In contrast, the A2 antagonist 3,7-dimethyl 1-propargyl-xanthine tended to worsen the neutrophil induced dysfunction of the heart, recovery amounting to 18(2)% (n = 5). CONCLUSIONS: Even after brief ischaemia, neutrophils introduced into the coronary system can exacerbate reperfusion injury. Adenosine, through its A1 receptor, and PAF appear to play a significant role as mediators of this action. PMID- 7796453 TI - Preischaemic as well as postischaemic application of a calcium antagonist affords cardioprotection in the isolated guinea pig heart. AB - OBJECTIVE: The aim was to answer the following questions: (1) Does treatment with calcium antagonists have to be begun before ischaemia or is postischaemic application also protective? (2) When applied before ischaemia, do calcium antagonists have to depress preischaemic cardiac function in order to elicit protection? (3) Is cardioprotection a matter of improved reflow or do the agents influence the degree of oxidative injury during reperfusion? METHODS: Isolated working guinea pig hearts underwent ischaemia (15 min) and reperfusion (15 min). The calcium antagonist gallopamil was given either before (0.1 nM and 1 nM) or after ischaemia (0.1 nM) during early reperfusion (first 5 min). Recovery was defined as postischaemic compared to preischaemic external heart work, expressed in percent. Oxidative stress was assessed by the release of glutathione (GSH). Lactate release served as a measure of the ischaemic challenge. The ability of gallopamil to scavenge oxygen radicals directly was investigated in an in vitro chemiluminescence assay. RESULTS: Pump function of control hearts recovered to only 28% after reperfusion. Pretreatment with 0.1 and 1 nM gallopamil improved recovery to the same extent (48.7% and 43.4%, respectively); however, postischaemic application of 0.1 nM gallopamil afforded equal protection (45.4% recovery). Only the higher concentration of 1 nM gallopamil depressed preischaemic external heart work (by 11%). During earliest reperfusion (1-5 min), release of GSH only tended to be lower in treated hearts. During the subsequent minutes of reperfusion (5-15 min), release of GSH was significantly less in hearts postischaemically treated with 0.1 nM gallopamil (40 pmol.min-1 v 940 pmol.min-1 for controls). In contrast, ischaemia-induced lactate release did not differ between the groups. Gallopamil did not scavenge reactive oxygen species in vitro. CONCLUSIONS: Short term postischaemic application of the calcium antagonist gallopamil is almost as effective at restoring pump function as preischaemic application which, in turn, does not have to depress preischaemic cardiac function in order to elicit protection. A reduction of oxidative stress during reperfusion seems to contribute to the beneficial effects of postischaemic application of gallopamil, but a direct oxygen radical scavenging activity of gallopamil is not involved. PMID- 7796454 TI - Animals in research. PMID- 7796455 TI - Actin, its associated proteins and metastasis. AB - In this short article we have overviewed the effect of transformation on AAPs. We have not dealt with molecules indirectly associated with actin which are modified by transformation, such as the catenins, cadherins, vinculin, and integrins [Tsukita et al., 1993], although their relationship with and importance to the transformed phenotype cannot be overemphasised. Similarly, alterations in polyphosphoinositide metabolism that occur in transformed cells may also promote or induce alterations in the microfilament cytoskeleton via interactions with proteins such as gelsolin, alpha-actinin, and MARCKS [Bretscher, 1993]. At present, there are no clear-cut rules regarding the effect that oncogenesis has on AAPs, since the expression level of one oncogenically modified AAP can vary from one tumour to another, even within the same type of tumour [Yamamoto et al., 1993]. This apparent inconsistency may well be because we are "playing with an incomplete pack of cards" [Pollard, 1993], or it may reflect this highly complex control mechanism in which any perturbation of the normal expression levels of actin/AAPs unbalances the delicate equilibrium which controls normal cell behaviour [Bray and Vasiliev, 1989]. For example, it is possible that oncogenically induced alterations to actin isoform expression [Lin et al., 1985] exert a downstream effect on actin-associated protein expression. Oncogenically induced actin based cell movements may be activated by alterations to either a single AAP or a synergistic functional unit of these molecules [Shapland et al., 1993; Vandekerckhove et al., 1990].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796457 TI - Dynein inner arm heavy chain identification in cAMP-activated flagella using class-specific polyclonal antibodies. AB - While studying cAMP-dependent dynein alpha-heavy chain phosphorylation, we found previously [Stephens and Prior, 1992: J. Cell Sci. 103:999-1012] that high salt extraction of sperm flagella from the mussel Mytilus edulis or the clam Spisula solidissima removed most visible dynein arms, accompanied by an amount of Mg+2 ATPase that correlated with the mass of dynein alpha- and beta-heavy chains removed. However, although almost devoid of ATPase activity, such extracted axonemes retained one third of the heavy chain mass as two sets of electrophoretically-distinct, vanadate-cleavable, non-phosphorylated proteins. To explore the nature of these dynein-like proteins, antibodies to the alpha- and beta-heavy chains were blot affinity-purified from a rabbit antiserum raised against gradient-purified Spisula 18-20S flagellar outer arm dynein. Although able to recognize common epitopes of the opposite chain type, neither the alpha- nor the beta-heavy chain antibody recognized the tightly-bound proteins in either species, proving that they are immunologically distinct. While the beta-antibody recognized its heavy chain homolog in gill cilia, the alpha-antibody did not, demonstrating immunological distinction between flagellar and ciliary dynein alpha-heavy chains. Immunization of a mouse with nitrocellulose strips containing one of the two tightly-bound Spisula flagellar proteins produced an antiserum that cross-reacted with each tightly-bound protein in both species and also recognized alpha- and beta-heavy chains. The anti-molluscan serum cross-reacted strongly with sea urchin sperm flagellar dynein B-, C-, and D-bands, considered to be inner arm components, but not with sea urchin outer arm alpha- or beta heavy chains. These data indicate that the electrophoretically and immunologically distinct, tightly-bound proteins of molluscan flagella are inner arm dynein heavy chains. PMID- 7796456 TI - Protein substrates for cGMP-dependent protein phosphorylation in cilia of wild type and atalanta mutants of Paramecium. AB - In the ciliated protozoan Paramecium, swimming direction is regulated by voltage gated Ca2+ channels in the ciliary membrane. In response to depolarizing stimuli, intraciliary Ca2+ rises, triggering reversal of the ciliary power stroke and backward swimming. One class of Ca(2+)-unresponsive behavioral mutants of Paramecium, atalanta mutants, cannot swim backward even though they have functional Ca2+ channels in their ciliary membrane. Several atalanta mutants were characterized with regard to several Ca(2+)-dependent activities, but no significant difference between wild type and the mutants was detected. However, one allelic group, atalanta A (initially characterized by Hinrichsen and Kung [1984: Genet. Res. Camb. 43:11-20]), showed a helical swimming path of opposite handedness from that of wild-type cells when detergent-permeabilized cells ("models") were reactivated with MgATP. When cGMP-dependent protein kinase purified from wild-type cells was added to atalanta A models, the handedness of the swimming path was reversed. Cyclic GMP stimulated in vitro phosphorylation of several proteins in isolated cilia, and the pattern of phosphoproteins was very similar for wild type and atalanta mutants, with one exception: a protein of 59 kDa was phosphorylated much less in the mutant ata A. When ciliary proteins were separated by gel electrophoresis and then phosphorylated "on blot" by purified cGMP-dependent protein kinase, phosphoprotein patterns were similar in wild type and ata mutants except that a 48 kDa protein (p48) from ata A3 was more heavily phosphorylated. This difference in p48 phosphorylation was also observed with cGMP-dependent protein kinase purified from ata A3 mutant cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796458 TI - Differentiation dependent expression of tensin and cortactin in chicken osteoclasts. AB - The expression and localization of tensin and cortactin were examined in osteoclast precursors in comparison with isolated osteoclasts on various substrates. Initially, the ability of hen monocytes to differentiate into osteoclasts was evaluated on plastic or glass, and compared to differentiation on bone. Specifically, monocytes were isolated from the medullary bones of egg laying hens maintained on a Ca-deficient diet. Differentiation was monitored morphologically and by quantitation of the ability to form Howship's lacunae in bone slices or resorb radiolabeled bone particles of 20-53 microns diameter. These cells differentiated into tartrate resistant acid phosphatase (TRAP) positive, bone resorbing, multinucleated syncytia in the presence of cytosine-1 beta-D-arabinofuranoside in a time dependent manner (day 1-6). Differentiation into osteoclast-like cells was similar whether cultured on plastic, on glass, or on bone. When compared to GAP-DH control levels, tensin and cortactin mRNA levels increased by 7- and 10-fold, respectively, by day 6. Tensin and cortactin protein levels also increased by 6- and 15-fold, respectively, by day 6. Immunofluorescence of differentiating precursors showed that tensin localized between regions of cell to cell contact and colocalized with vinculin in podosomes of osteoclast-like cells and of real osteoclasts. Cortactin immunofluorescence was not detectable in monocytes but localized inside tensin/vinculin podosome structures after fusion into osteoclast-like cells and in freshly isolated osteoclasts. Both tensin and cortactin were associated with attachment complexes used by osteoclast-like cells and osteoclasts to resorb bone. Specifically, punctate cortactin staining was observed inside tensin staining which formed a double ring structure at the membrane/bone interface of resorbing osteoclasts. These data showed that tensin and cortactin can be used as osteoclast differentiation markers, that participate in attachment complexes used to resorb bone, and that tensin may participate in the fusion process of osteoclast precursors. PMID- 7796459 TI - beta-Tubulin mutation suppresses microtubule dynamics in vitro and slows mitosis in vivo. AB - Microtubule (MT) dynamics vary both spatially and temporally within cells and are thought to be important for proper MT cellular function. Because MT dynamics appear to be closely tied to the guanosine triphosphatase (GTPase) activity of beta-tubulin subunits, we examined the importance of MT dynamics in the budding yeast S. cerevisiae by introducing a T107K point mutation into a region of the single beta-tubulin gene, TUB2, known to affect the assembly-dependent GTPase activity of MTs in vitro. Analysis of MT dynamic behavior by video-enhanced differential interference contrast microscopy, revealed that T107K subunits slowed both the growth rates and catastrophic disassembly rates of individual MTs in vitro. In haploid cells tub2-T107K is lethal; but in tub2-T107K/tub2-590 heterozygotes the mutation is viable, dominant, and slows cell-cycle progression through mitosis, without causing wholesale disruption of cellular MTs. The correlation between the slower growing and shortening rates of MTs in vitro, and the slower mitosis in vivo suggests that MT dynamics are important in budding yeast and may regulate the rate of nuclear movement and segregation. The slower mitosis in mutant cells did not result in premature cytokinesis and cell death, further suggesting that cell-cycle control mechanisms "sense" the mitotic slowdown, possibly by monitoring MT dynamics directly. PMID- 7796460 TI - Purification of microtubule associated protein MAP1B from bovine brain: MAP1B binds to microtubules but not to microfilaments. AB - A simple procedure for the purification of MAP1B from bovine brain is described. The procedure requires two ion-exchange chromatographic steps and results in > 95% pure MAP1B with a typical recovery of about 25-30 mg/kg of brain tissue. SDS PAGE analysis of the purified protein shows that it is composed of a high molecular mass (330kDa) heavy chain and two low molecular mass (32kDa and 18kDa) associated light chains. The estimated stoichiometry of heavy chain:light chain is 1:2 and 1:0.2 mole/mole protein for the 32kDa and 18kDa light chains respectively. Western blotting, using monospecific monoclonal antibodies, shows that only the heavy chain is recognised by the anti-MAP1B antibody and is not immunostained by either the MAP1A or MAP2 monoclonal antibodies. Purified MAP1B binds efficiently to both unpolymerised tubulin and polymerised tubulin and co sediments with taxol-stabilised microtubules. Co-incubation experiments show that MAP2 can compete with MAP1B binding to microtubules, indicating common or overlapping sites. However, MAP1B binds to neither G-actin nor F-actin nor co sediments with F-actin, suggesting that it is not an actin-binding protein. PMID- 7796462 TI - Axial rotation in rat embryos: involvement of changes in the shapes and arrangement of cells. AB - Rat embryos at the head-fold stage (9.5 days of gestation) were cultured for 32 hours in rat serum. Embryos rotated their axes (changing from the shape of a concave mid-region to that of a convex mid-region) during the last 5 hours of culture (from 27 h to 32 h in culture). Addition of 0.1 micrograms/ml cytochalasin D to the culture medium for this 5-hour period prevented axial rotation in the embryos and disturbed the appearance of microfilaments in the dermatome, the dorsal region of the trunk neural tube, and the dorsal epidermis. During the period of axial rotation, the dermatome and the dorsal epidermis extended and showed the arrangement of microfilaments along the cranio-caudal axis in the control embryos but not in the treated embryos. The dorsal region of the trunk neural tube in the control embryos consisted of a seam of neuroepithelial cells in which microfilaments were apparently arranged along the cranio-caudal axis but the region in the treated embryos was crowded with the neuroepithelial cells piled up randomly and microfilaments showed no arrangement. These results suggest that changes in the shapes and arrangement of the cells in the dermatome, the dorsal region of the trunk neural tube, and the dorsal epidermis cause extension of these tissues along the cranio-caudal axis and result in axial rotation. Microfilaments may play an essential role in changes in the shapes and arrangement of the cells in these tissues. PMID- 7796461 TI - A 62-kDa mitotic apparatus protein required for mitotic progression is sequestered to the interphase nucleus by associating with the chromosomes during anaphase. AB - A protein component of 62-kDa (p62) in the mitotic apparatus of the sea urchin embryo has been shown to be important for the proper progression of mitosis [Dinsmore and Sloboda, 1989: Cell 57:127-134]. To study the subcellular distribution of p62 during the cell cycle of sea urchin embryos, indirect immunofluorescence microscopy was used coupled to a modified detergent extraction procedure. The improved fluorescent images obtained by this procedure provide new information concerning the subcellular localization of p62 during the cell cycle that could not be obtained with previous conventional staining procedures [Johnston and Sloboda, 1992: J. Cell Biol. 119:843-854]. Using affinity purified antibodies to p62, we observed a cell cycle-dependent localization of p62 to the chromosomes/chromatin. Prior to nuclear envelope breakdown of the first or second cell cycle, p62 localizes to chromatin in the nucleus. During mitosis, p62 associates with the region of the spindle occupied by the microtubules of the mitotic apparatus. As anaphase proceeds, but before the nuclear envelope reforms, p62 becomes progressively associated with the chromosomes. Thus, p62 is incorporated into the forming interphase nucleus due to its association with chromosomes during late anaphase, rather than by active translocation into the newly formed daughter nuclei through the nuclear pores. The protein is not unique to marine embryos, as demonstrated by immunofluorescence of Y-1 cells, a mouse adrenal tumor cell line. In these cells, the localization of p62 is similar to the localization of the protein in echinoderm embryos, suggesting its possible function in mitotic progression in mammalian somatic cells as well. PMID- 7796463 TI - Alterations of expression of the cytoskeleton after immortalization of human fibroblasts. AB - Human diploid fibroblasts (HDF) have a limited in vitro lifespan of population doubling level (PDL) 50-70. The molecular mechanism underlying cellular senescence and immortalization is not thoroughly understood. It has been reported that the cytoskeleton has diverse functions and may have a role in growth regulation through association with other cellular components. To shed light on the relationship between functions of the cytoskeleton and senescence or immortalization, we investigated the alterations in gene expression after immortalization and measured the amounts of mRNAs for talin, vinculin, alpha actinin, tropomyosin 1 (TM1), vimentin, lamin A and C, and alpha-tubulin by slot blot and Northern blot analyses. We found that the mRNAs for vinculin and vimentin were reduced and the mRNA for lamin A was increased in immortalized cells. We also studied the cytoskeletal protein levels and their intracellular distributions by Western blot analysis and immunostaining. Most of the proteins studied behaved in a way similar to the mRNAs through senescence and immortalization. Vinculin, tropomyosins and vimentin showed their altered distributions in immortalized cells. PMID- 7796464 TI - An HL-60 variant cell line defective in cholesterol synthesis. AB - Human promyelocytic leukemia cell line, HL-60, is known to proliferate exponentially in a serum-free synthetic medium supplemented with insulin and transferrin (BREITMAN, T.R. et al. (1980). Exp. Cell. Res., 126: 494-498). Among four HL-60 cell lines tested in this medium (serum-free medium), however, a cell line, HL-60/Biken ceased to proliferate after two days culture and most of the cells died within a week. Addition of purified serum lipoprotein (LDL or HDL) to the serum-free medium almost completely restored the proliferating activity of the cells. Total lipids extracted from the lipoproteins could replace the lipoproteins in promoting cell proliferation. Among various lipid components of the lipoproteins, only cholesterol showed a high stimulatory effect on cell proliferation, whereas other lipids tested were ineffective, except for sphingomyelin, cerebroside, and phosphatidic acid which showed limited stimulatory effects. As for the intermediates of cholesterol biosynthesis, desmosterol was also effective, whereas lanosterol was rather inhibitory. Chromatographic analyses of the lipids synthesized by HL-60/Biken cells and wild type cells (HL-60/RCB) cultured in serum-free medium, clearly demonstrated that, in HL-60/Biken cells, cholesterol synthesis was almost completely blocked and lanosterol was accumulated 10-fold that in wild type HL-60/RCB cells. All of these results indicate that HL-60/Biken is a variant cell line defective in cholesterol synthesis in the process synthesizing desmosterol from lanosterol. The variant HL-60 cells showed a marked resistance to cell differentiation along both monocytic and granulocytic pathways when compared with wild type HL-60 cells. The cell line may be useful for the study of the role of cholesterol in cell differentiation. PMID- 7796465 TI - Cellular structure and function of rat fat cells in the primary culture. AB - A primary culture of undigested fat tissue fragments was used to obtain fat cells in vitro. On day 2 of culture, immature fat cells, which are fibroblast-like fat cells containing fine lipid droplets, appeared, surrounding the fat tissue fragments, and began to proliferate extensively. Afterwards, these fibroblast like fat cells grew to become multilocular fat cells containing larger intracytoplasmic lipid droplets, and differentiated further into unilocular fat cells containing a single large intracytoplasmic lipid droplet. Treatment with dibutyryl-cAMP, which is a second messenger of the lipolytic factor, caused the cultured fat cells to retract, and the intracytoplasmic lipid droplets of those fat cells became finely granulated and decreased along with an increase of hormone-sensitive lipase activities. Conversely, administration of insulin caused the lipid droplets in the fat cells to increase and become larger along with an increase of alpha-glycerophosphate dehydrogenase activities. These findings indicate the occurrence of lipolysis and lipogenesis of fat cells in vitro. Immuno-cytochemistry revealed that vimentin surrounded intracytoplasmic lipid droplets, and became distinct with an increase of lipid droplets through lipogenesis in the fat cells. Vimentin seems to be correlated to the behavior of lipid droplets in the fat cells. Fat cells in this study showed the appropriate cellular structures and functions in response to stimulation of lipolysis and lipogenesis under culture conditions. It is expected that in vitro culture of fat cells will facilitate cell biological elucidation of obesity in the future. PMID- 7796466 TI - Expression and phosphorylation of BiP/GRP78, a molecular chaperone in the endoplasmic reticulum, during the differentiation of a mouse myeloblastic cell line. AB - To determine the functional significance of endoplasmic reticulum chaperones in hematopoietic cells, we analyzed the expression and post-translational modification of BiP/GRP78 and GRP94 as well as the cytoplasmic chaperones HSP70 and HSC70 during the differentiation of a mouse myeloid leukemia cell line, M1. The amounts of BiP/GRP78 and GRP94 increased several-fold when M1 cells were induced to differentiate into macrophage-like cells by treatment with interleukin 6 (IL-6). Synthesis began to increase at 4 hr after IL-6 treatment. The phosphorylated form of BiP/GRP78 increased during the later stages of differentiation. These data suggested that the chaperone activity of BiP/GRP78 and GRP94 may be needed for differentiated macrophage-like cells or for the differentiation event itself, and that functionally different BiP/GRP78 accumulate during the differentiation of M1 cells. PMID- 7796467 TI - Distribution of PCNA during postblastoderm cell division cycles in the Drosophila melanogaster embryo: effect of a string- mutation. AB - We used immunocytochemical methods and a specific antibody to identify proliferating cell nuclear antigen (PCNA) in Drosophila embryos during the postblastoderm cell division cycles. The strong nuclear staining observed during interphase disappeared at prophase, staining remained nil throughout the remaining mitotic (M) phases and reappeared in nuclei at the next interphase. As the embryos with the homozygous string- mutation sustained the strong staining signal in nuclei throughout embryonic development, disappearance of the staining signal probably depends on string function and is coupled with the onset of mitosis. When cells in embryos were arrested at M phase following treatment with TN-16 or Vinblastine, the staining signal with the anti-PCNA antibody was lost. However, Western blots showed that the level of PCNA protein in M phase-arrested embryos did not decrease. Therefore, the disappearance of staining signals is apparently due to reorganization of PCNA protein in the multiprotein complex in nuclei, rendering it inaccessible to the antibody, rather than to the degradation of PCNA protein. In contrast to findings in developing embryos, cultured Drosophila Kc cells stained strongly with the anti-PCNA antibody, during both interphase and the M phase. In genetic crossing experiments of transgenic flies carrying the lacZ gene under the control of the PCNA gene regulatory region (-607 to +137 with respect to the transcription initiation site) with string- mutant files, the PCNA gene promoter seems to function in a manner independent of cell cycle progression or of functions of the string gene. PMID- 7796468 TI - Visualization of a single myelination process of an oligodendrocyte in culture by video microscopy. AB - We described the initial events in the interaction between an oligodendrocyte process and an axon in culture utilizing video time-lapse microscopy. Myelination of an axon by the lamellipodium of an oligodendrocyte was achieved in several steps of cellular process development and coordinated interaction between axon and oligodendrocyte. The initial stage of contact included the formation of a lamellipodium process at the end of an oligodendrocyte process. It appeared that this process contacted the axon several times and was then retracted, and that the filopodia and lamellipodium underwent morphological changes prior to the onset of the myelination. In the second stage, the lamellipodium appeared to thicken and anchor to the axon. Finally, when rippling of the lamellipodial ruffling occurred, the angle between the anchoring filopodium and the axon changed depending on the direction of lamellipodial movement, and the lamellipodium, which was folded in layers, wrapped around the axon like a transverse wave in one motion as observed on the video screen. Thereafter, the lamellipodium assumed a "bursting" form within minutes in real time. This is the first comprehensive overview of how an oligodendrocyte plasma membrane wraps around an axon to form myelin. PMID- 7796469 TI - Mechanism of the change in shape of human erythrocytes induced by lidocaine. AB - We studied the mechanism of the lidocaine-induced shape change in human erythrocytes. Immunohistochemical analysis of erythrocytes using spectrin specific antibodies revealed aggregation of fluorescence in lidocaine-treated cells, while the fluorescence was distributed diffusely in untreated cells. The intracellular pH in lidocaine-treated erythrocytes was examined by flow cytometry of the cells labeled with 3'-acetyl-2'-carboxy-ethyl-6',7'-(dihydropyran-2'-one) 5-carboxyfluoresc ein diacethoxymethylester (BCECF-AM), and was found to decrease with increasing concentrations of lidocaine. Pre-treatment of erythrocytes with acetazolamide, an inhibitor of carbonic anhydrase, inhibited the lidocaine induced spectrin aggregation and decrease in intracellular pH. When erythrocytes were incubated in medium containing bafilomycin A1, an inhibitor of V-ATPase, followed by incubation with lidocaine, the cells changed shape slightly and the intracellular pH showed a small decrease in comparison with control. Spectrin dimers extracted from membranes normal erythrocytes were incubated in buffers of various pHs and analyzed by SDS-PAGE. The amounts of spectrin dimers and tetramers decreased, while that of oligomers increased with decreasing pH. These results suggest that the lidocaine-induced shape change in human erythrocytes may occur by the conformational change of spectrin in a process that may be mediated by carbonic anhydrase and activation of V-ATPase. PMID- 7796471 TI - Quantitative cryoimmunogold electron microscopic studies on induction of serine: pyruvate aminotransferase in rat liver mitochondria by administration of glucagon. AB - Induction of mitochondrial serine: pyruvate aminotransferase (SPT) in rat liver by administration of glucagon was studied quantitatively by immunoblot analysis and cryoimmunogold electron microscopy. Immunoblot analysis revealed that two daily injections of glucagon produced marked increase of SPT protein mass to a level as much as 18 times that of the untreated rat. Cryoimmunogold electron microscopic analysis showed that the labeling density of the mitochondria increased in a parallel manner. Thus the induction of SPT analyzed by two methods showed an excellent correlation with a relative correlation coefficient of 0.98, indicating that the induction of SPT can be analyzed quantitatively by immunogold electron microscopy on cryoultrathin sections. PMID- 7796473 TI - [Study on the effect of using medicated intratracheal tube pad in the prevention and care of tracheotomy]. PMID- 7796472 TI - Establishment of cell lines from multipotent epithelial sheet in the budding tunicate, Polyandrocarpa misakiensis. AB - We report here the in vitro culture of the atrial epithelium, which is the major formative tissue of the budding tunicate, Polyandrocarpa misakiensis. Preliminary studies suggested that both pH and osmotic pressure of the basic seawater medium should be lowered significantly (pH 6.8, 800-830 mOsm). In the growth medium consisting of modified millipore-filtered seawater, Dulbecco's modified Eagle medium and 3% fetal bovine serum, cells spread out from the epithelial explant and proliferated with a doubling time of about 13 hours. They could be cloned and cultured successively. They contained the Polyandrocarpa lectin gene, showing that they were indeed of tunicate origin. At a low cell density (< 3 x 10(2) cells/mm2), clonal cells took a spherical form and contained several granules in the cytoplasma. At a high cell density (> 3 x 10(4) cells/mm2), on the other hand, they gave rise to smaller cells without any specialized features and, finally, to dark flattened cells. Consistent with this observation, confluent cells lost the atrial epithelium-specific antigen, which reappeared on the cell surface when they were re-plated at a low density. In conclusion, we have established for the first time tunicate cell lines. They appeared to differentiate and dedifferentiate repeatedly in our culture system. PMID- 7796470 TI - Hemocytes release phenoloxidase upon contact reaction, an allogeneic interaction, in the ascidian Halocynthia roretzi. AB - Contact reaction is the morphological expression of allogeneic recognition by hemocytes in the ascidian, Halocynthia roretzi; namely they undergo an exocytotic burst upon contact with non-self (allogeneic) hemocytes in vitro. We have found that contact reaction is accompanied by a burst of cyanide-insensitive oxygen consumption that, unlike exocytotic events of mammalian phagocytes, is Ca(2+) dependent and does not culminate in the production of superoxide anions or H2O2. Instead, the burst is due to the release of phenoloxidase from hemocytes as known for the self-defense systems in insects and crustaceans. The activity of phenoloxidase released from hemocytes corresponds well to the degree of contact reaction observed under the microscope. Therefore, it is possible to quantify the contact reaction simply by measuring the activity of phenoloxidase released from hemocytes into the medium. PMID- 7796474 TI - [Study on the factors correlated with the development of diaper rash of the newborn]. PMID- 7796475 TI - [Speech rehabilitation of aphemia after cerebral infarct]. PMID- 7796477 TI - [Care of congenital choledochocystectomy of infants under three]. PMID- 7796476 TI - [Care of nerve root type cervical spondylosis treated by blocking the inferior cervical roots]. PMID- 7796479 TI - [The correlation of psychosis with social environment and psychological factors and the management of patients]. PMID- 7796478 TI - [The lying position of newborn pneumonia]. PMID- 7796480 TI - [Care of pediatric pneumonia from the viewpoint of the characteristics of pediatric esophageal dynamics]. PMID- 7796481 TI - [Care of nasopharyngeal cancer patients after radiotherapy]. PMID- 7796483 TI - [Microcomputer used in burn nursing records]. PMID- 7796482 TI - [Techniques of puncture of the maxillary sinus in children]. PMID- 7796484 TI - [Comparison of evaluation of head nurses using the grey cluster method and the poll method]. PMID- 7796485 TI - [Defects in nursing document writing and measures to prevent them]. PMID- 7796486 TI - [A tentative research project of adding nursing applied anatomy in nursing education at polytechnic schools]. PMID- 7796487 TI - [Management and training of clinical teaching nursing staff]. PMID- 7796489 TI - Annual meeting of the Canadian Anaesthetists' Society. Ottawa, Ontario, June 23 27, 1995. Refresher course outlines and abstracts. PMID- 7796488 TI - Properties of alkaline phosphatase in the gingival crevicular fluid. AB - The isoenzymic properties of the alkaline phosphatase (ALP) of the gingival crevicular fluid (GCF) were investigated and compared with those in other cells, such as human polymorphonuclear leukocytes (PMNs), and human periodontal ligament cells (PDLs), and with those of three species of periodontopathic bacteria: Porphyromonas gingivalis 381 (P. gingivalis), Prevotella intermedia ATCC25611 (P. intermedia), and Capnocytophaga sputigena ATCC33123 (C. sputigena). The biochemical properties of the isoenzymes were analyzed by the following methods: enzyme assays, inhibition pattern using three chemical inhibitors, 4 to 20% gradient polyacrylamide gel electrophoresis, thermostability, immunological specificity, and phosphatidylinositol-specific phospholipase C (PI-PLC) treatment. The inhibition experiment showed that ALP of the PMNs and PDLs possessed almost the same enzymatic properties of tissue-nonspecific ALP (bone/liver/kidney; TNSALP), and the ALP of the three species of periodontopathic bacteria possessed specific properties that were different from those of TNSALP, intestinal, or placental ALP. The ALP of the GCF was only slightly susceptible to levamisole (1 mM), L-phenylalanine (20 mM), and SDS (1%). An electrophoresis thermostability test demonstrated that the enzyme activity of the GCF was separated into one or two bands. The main heat-labile slow band contained the phosphatidylinositol (PI)-moiety-anchored ALP and possessed immunological specificity against anti-bone type ALP. The minor fast band was heat stable and showed mobility similar to that in P. gingivalis. These results indicated that the ALP of the GCF consisted of several ALP isoenzyme types whose possible origins are considered to be derived from phosphatidylinositol (PI) anchored ALP and periodontopathic bacterial ALP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796490 TI - The calcium channel blocker scare. Lessons for the future. PMID- 7796491 TI - Meeting highlights. PMID- 7796492 TI - Thrombolysis for acute myocardial infarction. Why is there no extra benefit after hospital discharge? PMID- 7796493 TI - Familial hypertrophic cardiomyopathy. Nonsense versus missense mutations. PMID- 7796494 TI - Has improvement in PTCA intervention affected long-term prognosis? The NHLBI PTCA Registry experience. AB - BACKGROUND: The NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry followed 1345 consecutive patients with first PTCA between 1977 and 1981 (registry 1) and 2136 consecutive patients with PTCA between 1985 and 1986 (registry 2). Changes in patient selection and in immediate and 1-year outcome are presented. This report extends to 5 years the comparison of the effects of early and more recent management with PTCA. METHODS AND RESULTS: Sixteen participating centers entered consecutive patients who had angioplasty for the first time between 1977 and 1981 and between 1985 and 1986. Patients with recent myocardial infarction (MI) were excluded. Vessel disease was defined according to the Coronary Artery Surgery Study. Successful dilatation required > or = 20% reduction in luminal narrowing and < 50% lumen diameter stenosis after intervention. Routine annual follow-up was conducted by telephone interview. The product-limit method was used to estimate freedom from untoward events, Cox regression analysis to model relative risk and adjusted relative risk of events between the two registries, and logistic regression when the exact time of outcome (such as recurrence of symptoms) was not known. Long-term event rates were computed by vessel disease for all patients and for the cohort of patients with initially successful PTCA. After adjustment for extent of disease, diabetes, prior bypass surgery (CABG), hypertension, age, and sex, the 5-year risk of death was similar in the two registry cohorts. However, rates of MI, CABG, and a combined outcome measure of death, MI, and/or CABG were significantly lower in the registry 2 cohort both for all patients and for patients who were initially treated successfully. Use of repeated PTCA was higher, and freedom from symptoms without adverse events was significantly better in the latter cohort. CONCLUSIONS: Compared with registry 1, the management of the registry 2 cohort resulted in lower 5-year morbid event rates and reduced CABG operations. Mortality rates remained similar. When symptomatic status was considered in combination with events, a significantly better outcome was seen overall and in the initially successful cohort. In registry 2, repeated PTCA was used with much greater frequency early after the initial procedure. PMID- 7796495 TI - Long-term outcome of women compared with men after successful coronary angioplasty. AB - BACKGROUND: Women who undergo coronary angioplasty have a higher in-hospital mortality than men, although much of this difference can be accounted for by their poorer clinical characteristics at the time of their procedures. However, whether or not there are important long-term differences in outcome between women and men after coronary angioplasty is not clear. METHODS AND RESULTS: A retrospective analysis was performed of 3027 consecutive patients (824 women and 2203 men) who underwent successful angioplasty and who have been followed continuously for a mean of 5.5 years (range, 0.5 to 14 years). Follow-up is 100% complete. Event-free survival was assessed by the Kaplan-Meier method, and clinical end points were also examined by Cox proportional-hazards models to account for important baseline differences when appropriate. There was a trend toward lower survival among women during follow-up, but this was not significant (P = .06). The relative risk of death among women compared with men after adjustment for baseline differences was 0.94 (CI, 0.76 to 1.15; P = NS). No significant sex differences in occurrence of Q-wave myocardial infarction were observed. Women were less likely to remain free of angina after 10 years (34% versus 37%, respectively; P = .008), but after adjustment for baseline differences, this difference was not significant (relative risk of angina, 1.07; CI, 0.95 to 1.21). Women tended to have less coronary artery bypass surgery performed during follow-up (P = .06); adjusting for baseline differences made this difference more significant (relative risk, 0.79; CI, 0.64 to 0.96; P = .02). Among patients who were not treated in the setting of acute infarction, no sex differences in survival and freedom from myocardial infarction were noted. CONCLUSIONS: After successful coronary angioplasty, the long-term prognosis for women is excellent and is similar to that observed in men. Risk-adjusted survival did not differ significantly between the sexes, but less frequent use of subsequent surgical revascularization was observed in women. PMID- 7796496 TI - Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators. AB - BACKGROUND: The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. METHODS AND RESULTS: Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively). CONCLUSIONS: Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization. PMID- 7796497 TI - Effect of acute and long-term smoking on myocardial blood flow and flow reserve. AB - BACKGROUND: Cigarette smoking is a major preventable risk factor for coronary artery disease and sudden cardiac death. However, the effect of acute and long term cigarette smoking on coronary vasodilatory capacity and myocardial flow reserve has not been quantified in humans. METHODS AND RESULTS: To examine the effect of short-term and long-term smoking, myocardial blood flow was quantified at rest and during dipyridamole-induced hyperemia (0.56 mg/kg) in 12 smokers (10 males and 2 females; mean age, 27 +/- 4 years) under baseline conditions (reflecting the effect of long-term smoking) and during short-term cigarette smoking with 13N ammonia, positron emission tomography, and a two-compartment model. Twelve sex- and age-matched nonsmokers served as control subjects. Smoking significantly increased the rate-pressure product at rest from 7525 +/- 1290 to 9160 +/- 1125 (P < .001 versus baseline), which was paralleled by a proportional increase in myocardial blood flow at rest (0.70 +/- 0.17 versus 0.88 +/- 0.17 mL.g-1.min-1; P < .05 versus baseline). In contrast, hyperemic blood flow declined from 2.23 +/- 0.35 at baseline (P = NS versus control) to 1.98 +/- 0.32 mL.g-1.min-1 during smoking (P < .01 versus baseline). Accordingly, the myocardial flow reserve declined from 3.36 +/- 0.83 in smokers at baseline to only 2.28 +/- 0.28 during smoking (P < .0001 versus baseline). Thus, myocardial blood flow and flow reserve were similar in young, long-term smokers and young, healthy nonsmokers. CONCLUSIONS: Short-term smoking increases the coronary vasomotor tone during dipyridamole-induced hyperemia and markedly reduces the myocardial flow reserve. In contrast, long-term smoking does not attenuate the coronary vasodilatory capacity in young individuals with a relatively short smoking history. It might be speculated that the short-term reduction in the coronary vasodilatory capacity during smoking could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for sudden cardiac death. PMID- 7796499 TI - Assessment of coronary artery distensibility by intravascular ultrasound. Application of simultaneous measurements of luminal area and pressure. AB - BACKGROUND: Atherosclerotic change in the coronary artery is associated with an impaired vessel wall distensibility. However, there are few data regarding the relation between vessel wall morphology and distensibility. Therefore, with intravascular ultrasound, we assessed coronary artery distensibility in angiographically normal coronary segments of humans. METHODS AND RESULTS: Data were analyzed at 35 angiographically normal coronary sites where circumferential or noncircumferential lesions were demonstrated by ultrasound in 22 patients (mean age, 55 years). After intracoronary injection of 500 micrograms nitroglycerin (NTG), coronary luminal area was measured with intravascular ultrasound (30 MHz, 3.5F to 4.3F, 1800 rpm). Intracoronary pressure was simultaneously measured with a 2F micromanometer-tipped catheter located at the left main coronary artery. The coronary distensibility index was calculated as 10 fold the ratio of luminal area change to intracoronary pressure change during a cardiac cycle. Another pressure-independent vascular stiffness index, beta, was derived by the following formula: beta = [ln(SBP/DBP)]/(dD/diastolic mean diameter), where SBP is systolic intracoronary pressure, DBP is diastolic intracoronary pressure, and dD is the difference between systolic and diastolic diameters. At the sites where luminal areas were measured, thickness of intima media complex, defined as the distance between the intimal leading edge and the adventitial leading edge, was determined as an index of the severity of atherosclerosis. In seven segments, distensibility index was determined before and after NTG injection to examine the effect of NTG on coronary distensibility. In all examined sites, including circumferential and noncircumferential lesions, the luminal area was 12.6 +/- 5.0 mm2 during systole and 11.6 +/- 4.6 mm2 during diastole, and the calculated coronary distensibility index ranged from 0 to 0.83 mm2/mm Hg. The thickness of the intima-media complex ranged from 0.12 to 1.30 mm, suggesting the presence of various grades of atherosclerosis even in the absence of angiographic lesions. There was a poor inverse correlation between thickness of the intima-media complex and distensibility index (r = .19, y = -0.17x + 0.41, P = .29). However, when noncircumferential lesions were excluded for evaluation, there was a significant inverse correlation between them (r = .58, y = -0.50x + 0.72, P < .01). Under these conditions, the thickness of the intima-media complex also correlated with the value of beta (X10(-1), which ranged from 0.28 to 3.99 (r = .70). After NTG injection, coronary distensibility increased by an average of 71% in the segments with a thin intima-media complex, whereas it did not substantially change in those with a relatively thick intima-media complex. CONCLUSIONS: These results suggest that coronary distensibility is impaired in the coronary sites accompanying occult atherosclerosis, none of which can be detected by the conventional angiography. NTG can augment coronary distensibility in the segments without a markedly thickened intima-media complex. We suggest that thickness of the intima-media complex can contribute to determining the coronary distensibility in clinical settings. PMID- 7796498 TI - In vitro responses of human peripheral small arteries in hypercholesterolemia and effects of therapy. AB - BACKGROUND: Studies in both animals and humans with raised lipid levels have demonstrated abnormalities in vascular function usually manifested by an impairment in endothelium-dependent vasorelaxation. This is believed to be an early event in atheroma formation. There are few data on the effects on vascular function in humans of lowering serum lipids. We conducted a study to investigate the effects of cholesterol reduction on the in vitro function of human peripheral small arteries in middle-aged patients with hypercholesterolemia. METHODS AND RESULTS: Subcutaneous gluteal fat biopsies were taken from 18 hypercholesterolemic (HC) patients (mean +/- SEM serum total cholesterol, 9.7 +/- 0.57 mmol/L) and 16 age- and sex-matched control subjects (mean cholesterol, 4.69 +/- 0.18 mmol/L). Subcutaneous small arteries (internal diameter, < 330 microns) were dissected and mounted on a wire myograph for isometric tension measurements. The HC patients showed impaired relaxation to acetylcholine (10(-9) to 10(-6) mol/L) after preconstriction with the thromboxane A2 analogue U46619 (10(-6) mol/L, mean maximum relaxation, 42.9 +/- 5.4%) compared with control subjects (85.7 +/- 4.0%, P < .00001). Incubation with the nitric oxide substrate L arginine (3 mmol/L) improved the endothelium-dependent vasorelaxation response to acetylcholine (70.9 +/- 6.0%, P < .01) in patients but not in control subjects. Also, there was a smaller but significant difference in responses to the endothelium-independent agent sodium nitroprusside (10(-9) to 10(-6) mol/L) between the HC group (mean maximum relaxation, 76.9 +/- 6.0%) and the control subjects (89.7 +/- 6%; P < .01). A total of 10 patients had a second gluteal skin biopsy and repeat functional studies after successful cholesterol-lowering therapy after a mean period of 9.9 +/- 4.7 months. A significant reduction in total and LDL cholesterol was achieved (5.29 +/- 0.2 and 3.23 +/- 0.21 mmol/L, respectively; P < .001). This restored vasorelaxation to control values in response to both acetylcholine (mean maximum relaxation, 83.3 +/- 3.8%; P < .0001) and sodium nitroprusside (87.9 +/- 4.8%, P < .01). Although both groups were normotensive, there were significantly higher blood pressures in the HC group compared with control subjects (139 +/- 4.1 versus 123 +/- 3.0 mm Hg systolic, P < .01; 84 +/- 1.3 versus 75 +/- 2.2 mm Hg diastolic, P < .01). There was no difference in initial blood pressures between the entire group of 18 and the 10 patients who had repeat biopsies. The blood pressures fell to control values after cholesterol reduction (129.33 +/- 4.93 mm Hg systolic and 72.33 +/- 2.93 diastolic mm Hg, P < .02 relative to pretreatment values). CONCLUSIONS: These results demonstrate abnormalities of both endothelium-dependent and independent relaxation in human peripheral small arteries that are normalized with effective lipid lowering. The changes in blood pressure may have been secondary to the improvement in vascular function. PMID- 7796500 TI - A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy of unknown etiology. Missense mutations of the cardiac beta-myosin heavy-chain (beta-MHC) gene that may be responsible for cardiac hypertrophy have been detected in patients with HCM. On the other hand, gross structural abnormalities in the cardiac beta-MHC gene, ie, an alpha/beta hybrid gene and partial deletion of the gene, have also been reported. The direct correlation between gross abnormalities and development of HCM is not well understood. METHODS AND RESULTS: We analyzed the structure of the cardiac beta-MHC gene from patients with HCM by using polymerase chain reaction-DNA conformation polymorphism analysis and found two sequence variations in exons 3 and 22 in one patient. These sequence variations at codon 54 (exon 3; nonsense mutation) and codon 870 (exon 22; Arg-to-His mutation) were identified by direct sequencing and dot-blot hybridization with allele-specific oligonucleotide probes. Relatives of this patient were examined for the mutations. It was revealed that the missense mutation was inherited from the affected father and the nonsense mutation from the unaffected grandmother through the unaffected mother. In addition, the missense mutation was also found in seven other patients from two other unrelated multiplex HCM families. CONCLUSIONS: The Arg870His mutation was suggested to cause HCM. In contrast, the gene with the nonsense mutation would encode for a cardiac beta-MHC protein of only 53 amino acid residues, which may be too short to be incorporated into the thick filament assembly of cardiac myosin chains and showed no dominant phenotype of heart disease. This is the first report of a nonsense mutation in the human cardiac beta-MHC gene. PMID- 7796501 TI - Reduced epicardial coronary vasodilator capacity in patients with left ventricular hypertrophy. AB - BACKGROUND: Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. METHODS AND RESULTS: Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 micrograms intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2 +/- 2.2 mm) than in control subjects (8.6 +/- 1.5 mm; P < .001); after 100 micrograms intracoronary nitroglycerin, it increased to 12.9 +/- 2.2 mm (6 +/- 5%) in those with LV hypertrophy and to 10.3 +/- 1.5 mm (21 +/- 8%; P < .001) in control subjects. An inverse relation between baseline circumferential length and its percent increase after nitroglycerin was found (r = -.71, P < .001). CONCLUSIONS: Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries. PMID- 7796502 TI - Prolonged kinetics of recovery of oxygen consumption after maximal graded exercise in patients with chronic heart failure. Analysis with gas exchange measurements and NMR spectroscopy. AB - BACKGROUND: Patients with chronic heart failure (CHF) often complain of prolonged dyspnea after exercise. The determinants of oxygen consumption after exercise in these patients are unknown. We hypothesized that the kinetics of oxygen consumption recovery after graded exercise was prolonged in parallel with the recovery of muscle energy stores, was not affected by the exercise level, and could be used to assess the circulatory response to exercise. METHODS AND RESULTS: Seventy-two patients with CHF in Weber's class A (n = 28), B (n = 21), and C/D (n = 23) and 13 healthy subjects performed maximal upright bicycle exercise with breath-by-breath respiratory gas analysis. Kinetics of recovery of ventilation (VE), oxygen consumption (VO2), and CO2 production (VCO2) after exercise were characterized by T1/2, the time to reach 50% of the peak value. T1/2 VO2 (seconds) increased with the severity of CHF (97 +/- 17 for CHF A [P < .05 versus CHF B, P < .05 versus CHF C/D], 119 +/- 22 for CHF B [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF C/D], 155 +/- 55 for CHF C/D [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF B] compared with 77 +/- 17 for control subjects). T1/2 VCO2 and T1/2 VE also increased similarly with the worsening of CHF. T1/2 VO2 was correlated negatively with peak VO2 (r = .65) and was reproducible (r = .96). To study the relation between T1/2 VO2 and the duration of exercise, 10 healthy subjects and 22 patients underwent a second graded test at 75% and/or 50% of peak workload. T1/2 VO2 was minimally shortened, at only 50% of peak workload (P = .02). Finally, 19 patients underwent 31P nuclear magnetic resonance spectroscopy of the anterior compartment of the leg during exercise; the half-time of recovery of the ratio of inorganic phosphate to creatine phosphate (T1/2 Pi/PCr), reflecting the level of involvement of oxidative metabolism in the restoration of energetic metabolites after exercise, was linearly correlated with the half-time of VO2 recovery (r = .70, P < .01). CONCLUSIONS: Postexercise T1/2 VO2 increases when CHF worsens, perhaps in part a result of slower kinetics of recovery of muscle energy stores. The time course of oxygen consumption recovery may represent a simple new criterion for measuring the impairment of the circulatory response to exercise in CHF, even submaximal exercise. PMID- 7796503 TI - Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. AB - BACKGROUND: Angiotensin-converting enzyme (ACE) is involved in the metabolism of two major vasoactive peptides, converting angiotensin (Ang) I into Ang II and inactivating bradykinin. An insertion/deletion (I/D) polymorphism is present in the 16th intron of the ACE gene and is strongly associated with plasma and cellular ACE levels. Contrasting with the lack of relation between ACE gene polymorphism and blood pressure level, a large case-control study has shown that the deletion marker allele of the ACE gene was associated with an increased risk of myocardial infarction. The pathophysiological link between ACE gene polymorphism and cardiovascular events remains hypothetical. One hypothesis is that this polymorphism influences Ang II and bradykinin concentrations in the peripheral and/or local circulations through its effects on ACE levels in plasma and endothelial cells. The aim of this study was to investigate the effect of the ACE gene I/D polymorphism on blood pressure, plasma active renin, and aldosterone regulation in normal subjects. METHODS AND RESULTS: Twenty-four normotensive male volunteers homozygous for the ACE I/D polymorphism (12 DD and 12 II) received a renin inhibitor infusion (remikiren 0.1 mg.kg-1.h-1 for 130 minutes) to suppress endogenous Ang I and Ang II production. Forty minutes after initiating the remikiren infusion, an exogenous Ang I infusion was begun and increased gradually every 15 minutes from 1 to 10 ng.kg-1.min-1. Median (range) plasma ACE levels (mU/mL) were 39 (32 to 57) and 24 (12 to 30) in the DD and II groups, respectively. Remikiren suppressed plasma Ang I and Ang II, increased plasma active renin (from 23 +/- 12 to 154 +/- 161 pg/mL), decreased plasma aldosterone (from 106 +/- 42 to 82 +/- 33 pg/mL), and slightly decreased diastolic blood pressure (from -2.4 +/- 2.7 mm Hg). The blood pressure and hormonal responses to Ang I infusion after renin inhibition and the slope of the rise in plasma Ang II with increasing Ang I dose were identical in both groups, as was the plasma Ang I/Ang II ratio before (DD, 2.09 +/- 1.04; II, 2.59 +/- 0.76) and after (DD, 0.15 +/- 0.13; II, 0.09 +/- 0.03) combined renin inhibitor and Ang I infusion. CONCLUSIONS: Despite its association with a major difference in plasma ACE levels, the ACE I/D polymorphism did not influence the Ang II and plasma aldosterone production, plasma active renin decrease, or diastolic blood pressure increase induced by exogenous Ang I infusion, suggesting that ACE has no limiting influence on systemic Ang II generation and effects under these experimental conditions. PMID- 7796505 TI - Use of intravascular stents in systemic venous and systemic venous baffle obstructions. Short-term follow-up results. AB - BACKGROUND: Balloon-expandable intravascular stents are well accepted in the management of arterial obstructions. This study was undertaken to detail the immediate and short-term results of intravascular stent implantation in systemic venous and systemic venous baffle obstructions in children. METHODS AND RESULTS: Between September 1991 and June 1994, 12 patients had 21 stents implanted in 13 systemic venous obstructions, 1 patient having stents placed in 2 separate obstructions. In the baffle group, 4 of 13 obstructions were at the superior vena cava/right atrial junction after atrial baffling for transposition of the great arteries. One of 4 patients had complete obstruction requiring transseptal needle perforation before stent implantation. There was an immediate gradient reduction from 12 +/- 8.4 mm Hg (range, 4 to 20 mm Hg) to 1.3 +/- 1.9 mm Hg (range, 0 to 4 mm Hg, P = .05). The obstructed segment diameter increased from 3.5 +/- 3.9 mm (range, 0 to 8.5 mm) to 16 +/- 2.7 mm (range, 14 to 20 mm, P = .002). In the central vein group, 9 of 13 obstructions were in large central veins. Three of 9 patients had complete obstruction requiring transseptal needle perforation before stent implantation. There was an immediate gradient reduction from 10.3 +/- 8.5 mm Hg (range, 0 to 20 mm Hg) to 0.8 +/- 1.1 mm Hg (range, 0 to 3 mm Hg, P = .005). The obstructed segment diameter increased from 1.3 +/- 1.1 mm (range, 0 to 2.8 mm) to 9.4 +/- 1.7 mm (range, 7.6 to 12 mm, P < .001). There were no acute complications in either group. In the follow-up group, patients were scheduled for clinical follow-up at 3, 6, and 12 months with echocardiography or magnetic resonance imaging (MRI) at 3 or 6 months and for repeat cardiac catheterization at 12 months. All stents were patent by echocardiography or MRI when studied at follow-up. Cardiac catheterization in 6 of 12 patients, 2 to 13 months after stent, demonstrated that all stents remained patent without compression or fracture. Follow-up and immediate poststent gradients were not significantly different (1 +/- 1.6 versus 0.7 +/- 1.2 mm Hg, P = NS). Neointimal hyperplasia (5 of 6 patients) reduced the stent lumen only from 12.5 +/- 4.7 mm (range, 8 to 20 mm) to 10.6 +/- 4.7 mm (range, 4.5 to 17.7 mm, P = NS). No stents required redilation. One of 18 stents placed in series had "unlocked" and rotated in the venous lumen but remained fully patent to flow. CONCLUSIONS: Balloon-expandable intravascular stents can be safely and effectively used to relieve systemic venous and systemic venous baffle obstructions, even when obstruction is complete. Short-term follow-up suggests excellent continued patency, but further follow-up is required to observe for progression of neointimal hyperplasia. We postulate that balloon-expandable intravascular stents will become the treatment of choice for the relief of selected systemic venous and venous baffle obstructions in the pediatric population. PMID- 7796504 TI - Modification of the Fontan procedure. Superior vena cava to left pulmonary artery connection and inferior vena cava to right pulmonary artery connection with adjustable atrial septal defect. AB - BACKGROUND: A modification of the Fontan procedure with unidirectional cavopulmonary connection is described in which the superior vena cava (SVC) is connected to the left pulmonary artery (PA) and the inferior vena cava (IVC) is connected to the right PA via a lateral tunnel with a snare-controlled, adjustable atrial septal defect (ASD). This allows matching of the SVC and IVC flows with the lung of appropriate size. The obligatory left Glenn shunt provides an adequate arterial oxygen saturation, and the elevation in SVC pressure is well tolerated. The adjustable ASD allows selective decompression of the IVC that maintains cardiac output and reduces fluid accumulation in the serous cavities. METHODS AND RESULTS: Since March 1992, we have performed this procedure in 18 patients. There were 17 children and 1 adult. Median age was 3 years and 9 months (range, 13 months to 36 years). Six patients had been staged with a previous bidirectional Glenn shunt. Preoperative cardiac catheterization revealed a PA pressure of 13 +/- 2 mm Hg and a transpulmonary gradient of 5 +/- 3 mm Hg. Ventricular function was satisfactory in all patients. At the completion of bypass, the pressures in the SVC and IVC were 16 +/- 4 mm Hg and 10 +/- 3 mm Hg, respectively (P < .01). The left atrial pressure was 6.0 +/- 3.0 mm Hg and the arterial O2 saturation on 100% oxygen was 93 +/- 3%. There was one death as a result of intractable atrial arrhythmias. The remaining 17 patients had a mean hospital stay of 9.7 days (6 to 18 days). The length of pleural drainage was 7 +/ 3 days. The ASD was adjusted in 11 patients before discharge. Oxygen saturation at discharge was 85.4 +/- 4%. Nine patients had repeat catheterization. The ASD was completely closed in 6 patients, an average of 2.5 months after surgery (range, 3 weeks to 5 months). After ASD closure, the arterial oxygen saturation was 96 +/- 3%, and the SVC and IVC pressures were both 13 +/- 3 mm Hg. CONCLUSIONS: The Fontan procedure with unidirectional cavopulmonary connection and adjustable ASD has several advantages that may reduce mortality and morbidity for the high-risk Fontan candidate. PMID- 7796506 TI - Assessment of left-to-right intracardiac shunting by velocity-encoded, phase difference magnetic resonance imaging. A comparison with oximetric and indicator dilution techniques. AB - BACKGROUND: Velocity-encoded, phase-difference magnetic resonance imaging (MRI) has been shown to provide an accurate assessment of shunt magnitude in patients with large atrial septal defects, but its ability to determine shunt magnitude in patients with intracardiac left-to-right shunts of various locations and sizes has not been evaluated in a prospective and blinded manner. The objective of the present study was to determine whether velocity-encoded, phase-difference MRI can assess the magnitude of intracardiac left-to-right shunting in humans. METHODS AND RESULTS: Twenty-one subjects (15 women and 6 men; age range, 15 to 72 years) underwent velocity-encoded, phase-difference MRI measurements of flow in the proximal aorta and pulmonary artery, followed immediately by cardiac catheterization. The presence of left-to-right intracardiac shunting was assessed with hydrogen inhalation, after which shunt magnitude was measured by the oximetric and indocyanine green techniques. Of the 21 patients, 12 had left-to right intracardiac shunting detected by hydrogen inhalation. There was a good correlation (r = .94) between the invasive and MRI assessments of shunt magnitude. In comparison to oximetry and indocyanine green, MRI correctly identified the 12 patients with a ratio of pulmonary to systemic flow (Qp/Qs) of < 1.5 (9 without intracardiac shunting and 3 with small shunts) and the 9 patients with a Qp/Qs of > or = 1.5 (6 with atrial septal defect, 1 with ventricular septal defect, 1 with patent ductus arteriosus, and 1 with both atrial septal defect and patent ductus arteriosus). CONCLUSIONS: Compared with measurements obtained during cardiac catheterization, velocity-encoded, phase difference MRI measurements of flow in the proximal great vessels can reliably assess the magnitude of intracardiac left-to-right shunting. PMID- 7796508 TI - Failure of heparin to inhibit intimal hyperplasia in injured baboon arteries. The role of heparin-sensitive and -insensitive pathways in the stimulation of smooth muscle cell migration and proliferation. AB - BACKGROUND: Heparin is a potent inhibitor of smooth muscle cell (SMC) growth and intimal hyperplasia in animal models but has been ineffective in inhibiting restenosis in humans. This difference may relate to flaws in clinical study design or, alternatively, to interspecies differences in SMC response to heparin. To determine whether heparin could inhibit intimal hyperplasia in a species more closely related to humans, we studied the effect of a low-molecular-weight heparin (LMWH) on baboon SMC proliferation and migration in culture and in arteries subjected to experimental angioplasty. METHODS AND RESULTS: LMWH or saline was infused continuously after experimental angioplasty of baboon peripheral arteries (six animals per group). After 28 days, bromodeoxyuridine (BrdU) was given to label proliferating cells, and balloon-injured arteries were perfusion-fixed in situ and removed for analysis. All arteries had reendothelialized (Evans blue dye exclusion). LMWH increased partial thromboplastin time (LMWH, 81.7 +/- 8.4 seconds versus saline, 34.7 +/- 0.8 seconds [mean +/- SEM]; P = .004) but failed to inhibit intimal thickening or SMC proliferation (intimal area: LMWH, 0.19 +/- 0.03 mm2 versus saline, 0.21 +/- 0.03 mm2; BrdU labeling: LMWH, 2.9 +/- 0.6% versus saline, 2.4 +/- 0.4%; P = NS). In culture, LMWH and standard heparin (100 micrograms/mL) significantly inhibited serum-induced but not platelet-derived growth factor (PDGF-BB)-induced SMC proliferation (% control, serum: LMWH, 60.5 +/- 4.0%, P = .0002; standard heparin, 29.4 +/- 8.2%, P = .0001; % control, PDGF-BB: LMWH, 117.7 +/- 11.3%, P = NS; standard heparin, 90.9 +/- 14.4%, P = NS) and SMC migration (% control, serum: LMWH, 15.3 +/- 1.9%, P = .0198; standard heparin, 26.4 +/- 13.8%, P = .0032; % control, PDGF-BB: LMWH, 98.5 +/- 14.3%, P = NS; standard heparin, 100.0 +/- 13.5%, P = NS). CONCLUSIONS: LMWH failed to inhibit intimal hyperplasia in a baboon angioplasty model. Furthermore, LMWH blocked serum-induced but not PDGF-BB induced SMC proliferation and migration in culture. Thus, heparin-sensitive and insensitive pathways exist for SMC activation. The relative importance of each pathway induced by injury may vary between species and thus account for different responses to heparin. PMID- 7796507 TI - An antibody against the exosite of the cloned thrombin receptor inhibits experimental arterial thrombosis in the African green monkey. AB - BACKGROUND: Thrombin inhibitors have been shown to be efficacious in animal models of thrombosis and in initial human clinical trials. It is unknown if their efficacy is due to their prevention of thrombin-mediated fibrin formation or to an inhibitory effect on thrombin-stimulated platelet activation. Appropriate tools to address this question have not been available. Therefore, to evaluate the role of the platelet thrombin receptor in intravascular thrombus formation, a polyclonal antibody was raised against a peptide derived from the thrombin binding exosite region of the cloned human thrombin receptor. This antibody serves as a selective inhibitor of the thrombin receptor for in vivo evaluation. METHODS AND RESULTS: The immune IgG (IgG 9600) inhibited thrombin-stimulated aggregation and secretion of human platelets. In contrast, it had no effect on platelet activation induced by other agonists including ADP, collagen, or the thrombin receptor-derived peptide SFLLR-NH2. IgG 9600 also inhibited thrombin induced aggregation of African Green monkey (AGM) platelets. By Western blot analysis, the IgG identified a protein of approximately 64 kD in homogenates of both human and AGM platelets. The effect of thrombin receptor blockade by this antibody on arterial thrombosis was evaluated in an in vivo model of platelet dependent cyclic flow reductions (CFRs) in the carotid artery of the AGM. The intravenous administration of IgG 9600 (10 mg/kg) abolished CFRs in three monkeys and reduced CFR frequency by 50% in a fourth monkey. Ex vivo platelet aggregation in response to up to 100 nmol/L thrombin was completely inhibited during the 120 minute postbolus observation period in all four animals. There was a twofold increase in bleeding time, which was not statistically different from baseline, and ex vivo clotting time (APTT) was not changed. The glycoprotein IIb/IIIa receptor antagonist MK-0852 and the thrombin inhibitor recombinant hirudin also demonstrated inhibitory effects on CFRs at doses that did not significantly prolong template bleeding time. Control IgG had no effect on CFRs, ex vivo platelet aggregation, bleeding time, or APTT. CONCLUSIONS: These results demonstrate that blockade of the platelet thrombin receptor can prevent arterial thrombosis in this animal model without significantly altering hemostatic parameters and suggest that the thrombin receptor is an attractive antithrombotic target. PMID- 7796510 TI - Absence of lethal reperfusion injury after 3 hours of reperfusion. A study in a single-canine-heart model of ischemia-reperfusion. AB - BACKGROUND: Whether reperfusion can cause necrosis of previously viable myocytes (lethal reperfusion injury) remains controversial. Numerous studies examined the ability of various agents to prevent or limit reperfusion injury, but the results were contradictory. In a single-canine-heart model of ischemia-reperfusion, we previously demonstrated that 5 minutes of reperfusion does not increase the transmural extent of necrosis. Since the 5-minute period of reperfusion is considered by some to be too short for the full manifestation of reperfusion injury, we reexamined the issue of lethal reperfusion injury using a modification of the single-heart model of ischemia-reperfusion that allowed extending the reperfusion period to 3 hours. METHODS AND RESULTS: In anesthetized, open-chest dogs, the distal half of the left anterior descending coronary artery (LAD) segment between the last diagonal branch and the apex was perfused via a shunt from the left carotid artery. The shunt was closed for periods of 90 to 180 minutes, depending on the ECG severity of ischemia, and reperfused for 3 hours. While the distal region was perfused from the carotid artery, the LAD was occluded proximal to the last diagonal branch for the same period of time as the distal region had been earlier. The time of occlusion was chosen such that the end of the occlusion period coincided with the end of the experiment. Thus, both regions of the LAD territory were subjected to identical periods of ischemia, but only the distal region was reperfused. At the end of the experiment, the boundary between the proximal (nonreperfused) and distal (reperfused) area was delineated by blue dye, and the heart was arrested, cut into slices 1 cm thick parallel to the LAD, and placed in triphenyltetrazolium chloride. The epicardial edges of necrosis in the reperfused and the nonreperfused regions were examined for any shift that might suggest a difference in the transmurality of necrosis. The areas of necrotic and viable myocardium were measured by planimetry within 1 cm on either side of the boundary. In all 14 dogs, the epicardial edges of necrosis ran as a single line across the boundary, and no shift was present. There was also no difference in the transmurality of necrosis between the reperfused and nonreperfused regions (64.9 +/- 20.7% versus 66.1 +/- 17.0% of left ventricular wall thickness, respectively, P = .32 by paired t test). CONCLUSIONS: In a single canine-heart model of ischemia-reperfusion, there was no evidence of lethal reperfusion injury after 3 hours of reperfusion. PMID- 7796509 TI - Pharmacodynamics of plasma nitrate/nitrite as an indication of nitric oxide formation in conscious dogs. AB - BACKGROUND: The present investigation was undertaken to better understand the production of nitric oxide (NO) in vivo as measured by alterations in plasma nitrite or nitrate in blood samples from studies in experimental animals or clinical studies in humans. METHODS AND RESULTS: Plasma samples were taken from the aorta, the coronary sinus, a peripheral vein in the leg (skeletal muscle), or the right ventricle (mixed venous) in chronically instrumented conscious dogs. Plasma nitrite was converted to NO gas in an argon environment by use of hydrochloric acid, and plasma nitrate was converted first to nitrite with nitrate reductase and then to NO gas with acid. Standard curves were constructed, and the amount of nitrite and nitrate in plasma was determined. The primary metabolite was nitrate, whereas nitrate was approximately 10% of the total and remained constant. In the resting dog, the only vascular bed with a positive arterial venous nitrate difference, evidence for production of NO, was the heart. Nitrate infusion into quietly resting dogs resulted in increases in plasma nitrate up to 38 +/- 3.4 mmol/L, increases in systemic arterial pressure, and a marked diuresis. The plasma half-life was calculated as 3.8 hours. The volume of distribution was calculated as 0.215 L/kg, or equivalent to the extracellular volume. CONCLUSIONS: These studies indicate that nitrate is a reliable measure of NO metabolism in vivo but that because of the long half-life, nitrate will accumulate in plasma once it is produced. Because of the large volume of distribution (21% of body weight versus the 4% of body weight usually attributed to plasma volume, the compartment in which nitrate is measured), simple measures of plasma nitrate underestimate by a factor of 4 to 6 the actual production of nitrate or NO by the body. In disease states, such as heart failure, in which renal function and extracellular volume are altered, caution should be exercised when increases in nitrate in plasma as an index of NO formation are evaluated. PMID- 7796511 TI - Endovascular stent design dictates experimental restenosis and thrombosis. AB - BACKGROUND: Vascular interventions that maximize initial lumen diameter provoke extensive neointimal hyperplasia but minimize its effects, causing long-term lumen size to be greater. Nevertheless, interventions such as endovascular stents, which increase lumen size above that achieved with balloon angioplasty, are subject to frequent thrombosis and restenosis. It has been unclear whether the response to stent-induced injury is determined solely by the degree of stent induced arterial expansion or whether the geometric configuration of the stent or the material left in contact with the vessel wall also contribute. METHODS AND RESULTS: We examined the vascular response to steel stents deployed in denuded rabbit iliac arteries for 14 days. In one set of experiments, the effects of sten configuration were examined, holding diameter, mass, surface area, and stent surface material constant. In another set, stent surface material was changed, with mass, configuration, and diameter unaltered. Changing stent configuration to reduce strut-strut intersections by 29% without affecting mass or surface area reduced vascular injury by 42%, thrombosis by 69%, and neointimal hyperplasia by 38%. Monocyte adhesion to stented arteries correlated linearly with vascular trauma and neointimal hyperplasia (r = .96, P < .01 for each). When the stainless steel surface was coated with an inert polymer material, vascular injury and neointimal hyperplasia were unchanged but thrombosis was eliminated. CONCLUSIONS: Surface material and geometric configuration of stents may be more important than postplacement diameter in determining neointimal hyperplasia and thrombosis. Alterations in configuration affect vascular injury and neointimal hyperplasia, while surface material plays a greater role in thrombosis. Monocytes may be important modulators of stent-induced intimal thickening. Clinical confirmation of these findings may alter coronary stent deployment techniques and future stent designs. PMID- 7796512 TI - Effect of cocaine on left ventricular function. Relation to increased wall stress and persistence after treatment. AB - BACKGROUND: To determine whether alterations in left ventricular (LV) function after a cocaine infusion are due to reduced myocardial contractility or changes in loading conditions, we examined LV function in 30 morphine-sedated, closed chest dogs. We also wanted to determine the time course of the effects of cocaine on LV function after the infusion was stopped. METHODS AND RESULTS: Two dimensional echocardiography and hemodynamics provided LV fractional shortening and end-systolic wall stress data. Radionuclide ventriculography was also performed. Four groups of dogs received saline or cocaine infusions of 10, 30, or 100 micrograms.kg-1.min-1. Cocaine was infused for 90 minutes with ECG and arterial pressure monitoring. Animals were monitored for an additional 120 minutes after the infusion ended. Arterial pressure rose over the course of the experiment in all four groups, but saline and cocaine 10 micrograms.kg-1.min-1 did not significantly change ejection fraction. Cocaine 30 and 100 micrograms.kg 1.min-1 acutely increased arterial pressure and heart rate but decreased ejection fraction from 0.64 +/- 0.06 to 0.45 +/- 0.08 and from 0.65 +/- 0.10 to 0.46 +/- 0.11, respectively. Additionally, cocaine 100 micrograms.kg-1.min-1 decreased fractional shortening from 36 +/- 9% to 23 +/- 12%. However, cocaine 30 and 100 micrograms.kg-1.min-1 also increased wall stress from 42 +/- 15 to 65 +/- 11 g/cm2 and from 37 +/- 15 to 90 +/- 33 g/cm2, respectively. These results were analyzed by use of the relation between wall stress and fractional shortening as an index of contractility. Fractional shortening after cocaine infusion was displaced downward as a result of increased wall stress rather than changes in contractility. In addition, alteration of afterload with phenylephrine (6 micrograms/kg) and sodium nitroprusside (10 micrograms/kg) before and during infusion of cocaine 100 micrograms.kg-1.min-1 showed similar regression lines for wall stress to fractional shortening. CONCLUSIONS: Ejection-phase indexes of LV function were reduced by cocaine in this model of conscious, sedated dogs, but effects were attributable to increased wall stress rather than to reduced myocardial contractility. These effects persisted for at least 2 hours after the infusion was stopped. PMID- 7796514 TI - Sudden loss of consciousness, dyspnea, and hypoxemia in a previously healthy young man. PMID- 7796513 TI - Erythromycin blocks the rapid component of the delayed rectifier potassium current and lengthens repolarization of guinea pig ventricular myocytes. AB - BACKGROUND: Administration of erythromycin to humans has been associated with lengthening of cardiac repolarization and even proarrhythmia. The objectives of our study were to describe effects of erythromycin on repolarization of isolated hearts and to determine effects of the drug on major K+ currents involved in cardiac repolarization. METHODS AND RESULTS: A first set of experiments was conducted in isolated, buffer-perfused guinea pig hearts electrically stimulated at a basic cycle length of 250 ms. In this model, erythromycin 10(-4) mol/L increased monophasic action potential duration measured at 90% repolarization (MAPD90) by 40 +/- 7 ms. Increase in MAPD90 was reproducibly observed in seven hearts studied. To study the mechanism of these effects on cardiac repolarization, a second set of experiments was performed in isolated guinea pig ventricular myocytes using the whole cell configuration of the patch-clamp technique. In these cells, erythromycin 10(-4) mol/L decreased by about 40% (P < .05 versus baseline) the time-dependent outward K+ current elicited by short depolarizations (250 ms) to low depolarizing voltages (-20 to 0 mV). In contrast, the drug was without significant effects on the time-dependent K+ current elicited by long pulses (5000 ms) to high depolarizing voltages (+10 to +50 mV), on the time-independent background current (mostly IKl), and on the slow inward calcium current. CONCLUSIONS: The outward time-dependent K+ current blocked by erythromycin in isolated guinea pig ventricular myocytes had characteristics similar to those described for IKr. Selective block of this component of IK gives an explanation for the effects of erythromycin on cardiac repolarization. These effects were observed at clinically relevant concentrations reached after intravenous administration of the drug and warn for potential interactions with other action potential-lengthening drugs. PMID- 7796515 TI - Images in cardiovascular medicine. Metallic mercury embolism. PMID- 7796516 TI - Anxiety and risk of coronary heart disease. PMID- 7796517 TI - Sidestream cigarette smoke and arteriosclerosis. PMID- 7796518 TI - Hemodynamic effects of sympathetic efferent reinnervation after orthotopic cardiac transplantation. PMID- 7796519 TI - Benefits of ventilation for CPR. PMID- 7796520 TI - Quantitative comparison of Acanthamoeba castellanii adherence to rigid versus soft contact lenses. AB - We evaluated quantitative differences in adherence of Acanthamoeba castellanii trophozoites and cysts to new unworn contact lenses as a function of contact lens type and duration of exposure. Daily wear soft (polymacon), disposable soft (etafilcon A), rigid gas permeable (RGP) (siloxane acrylate), and polymethylmethacrylate (PMMA) contact lenses were exposed to 1 x 10(5)/mL log phase A. castellanii (trophozoite:cyst ratio 90:10) for 10 seconds, 30 minutes, 60 minutes, and 120 minutes. The number of adherent organisms was determined by light microscopy and confirmed by scanning electron microscopy. Rates of cyst adherence were similar among contact lens types. We observed significantly greater adherence of trophozoites to RGP and PMMA lenses compared with soft contact lenses (P < 0.05). This difference in trophozoite adherence was significant at all four time periods (P < 0.05). Our findings show that A. castellanii trophozoites and cysts adhere to both soft and rigid contact lens types. We also found that although trophozoite adherence increases as a function of duration of exposure, adherent organisms were observed with exposure times as brief as 10 seconds. This suggests that all contact lens types may be at risk for Acanthamoeba attachment and that even minimal exposure times may be sufficient for lens contamination. PMID- 7796521 TI - Normal protein and glycoprotein profiles of reflex tears and trace element composition of basal tears from heavy and slight deposits on soft contact lenses. AB - We investigated the hypothesis that lacrimal component accumulation on soft contact lenses (SCL) may be induced by an abnormal protein, glycoprotein, or trace element composition of the tear fluid. Individual tear samples were collected from healthy non-SCL wearers (normal patients) and SCL wearers grouped as either "slight-depositor" or "heavy-depositor" following SCL spoilage rate and frequency. The reflex tear proteins were analyzed by three electrophoretic procedures: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on minigels, isoelectric focusing (IEF) on immobilized pH gradients (IPG 4-7), and two-dimensional separation combining IEF in the first dimension to orthogonal SDS-PAGE. After separation, the proteins were detected by silver staining and identified by immunologic probes. The reflex tear glycoproteins were analyzed by lectin affinity associated electrotransfer of SDS-PAGE with a panel of five biotinylated lectin probes: Canavalia ensiformis (Con A), Artocarpus integrifolia (Jacalin), glycine max (SBA), Ulex europaeus (UEA 1), and Triticum vulgaris (WGA) agglutinins. The basal tear trace elements were analyzed by Synchrotron Radiation X-ray Fluorescence. Despite the highly sensitive techniques used in the study, the profiles of reflex tear proteins, glycoproteins, and trace elements appeared to vary slightly among individuals. No evident qualitative difference in reflex tear fluid related to SCL wear or deposit formation susceptibility was found. The presence or absence of a particular protein, glycoprotein, or trace element could not be correlated with a different reactivity to SCL. However, potassium and carbohydrate residues having affinity with Jacalin and WGA presented little but not significant variations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796523 TI - Phototherapeutic keratectomy for the treatment of nodular subepithelial corneal scars in patients with keratoconus who are contact lens intolerant. AB - The management of keratoconus with contact lenses may be complicated by punctate epithelial keratopathy, epithelial breakdown, and nodular, raised subepithelial scars. We report four consecutive cases of contact lens intolerance due to pain in patients with keratoconus and raised, nodular scars. Excimer laser phototherapeutic keratectomy (PTK) was used to treat all patients. Follow-up ranged from 7 to 14 months (mean: 10 months). All patients resumed rigid gas permeable (RGP) contact lens wear 2 to 4 weeks after surgery. Visual acuities ranged from 20/40 to 20/70 before surgery and improved to 20/25 or better in all patients postoperatively. PTK flattened the central cornea by an average of 5.43 D (range: 1.13-10.19 D); and refractive cylinder was reduced an average of 4.00 D (range: 3.25-5.25 D). We conclude that PTK may delay or avoid penetrating keratoplasty in selected patients with keratoconus who are contact lens intolerant due to nodular subepithelial scars. PMID- 7796522 TI - Bacterial contamination in soft contact lens wearers. AB - We prospectively analyzed bacterial contamination in 15 soft contact lens wearing subjects. Contact lenses, cases, tips of saline solution bottles, and conjunctiva were cultured. Cultures were positive for 13 subjects (86.6%). Contamination was present in 13 contact lens cases (86.6%), 12 contact lenses (80.0%), nine saline solution bottles (60.0%), and in the conjunctiva of three patients (20.0%). Gram negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) were the most frequently isolated organisms. Staphylococcus aureus was the only gram-positive organism isolated. We discuss the possible sources of contamination, and emphasize the importance of contact lens care instruction. PMID- 7796524 TI - Videokeratography. AB - Our ability to assess corneal topography has improved tremendously in the last 10 years. Current placido disk-based videokeratography units have made the process of image analysis simple, yet current systems are not perfect in their quantitative assessment of human corneas. The choice of a system depends on the user's needs and the evaluation of the differences in hardware, software, format of data output, service, frequency of software updates, user friendliness, and control of focusing errors. This article reviews the development of technology for assessing corneal topography. PMID- 7796525 TI - Learning from others. PMID- 7796526 TI - Will young children comply and follow instructions to successfully wear soft contact lenses? AB - We fit eighty-five children between the ages of 11 years and 13 years, 11 months with soft contact lenses to study safety of soft contact lens wear in children. We report the results at 6 months of a 3 year longitudinal study. Contact lens care compliance, a critical factor in successful lens wear, was evaluated using a questionnaire. The questionnaire was completed by 74 subjects at dispensing and at 1-week and 6-months post-dipensing visits. Subjects found contact lens removal to be the easiest and lens insertion the most difficult procedures. After 6 months, 85% of the children correctly identified the purpose of lens care solutions, 90% knew that daily cleaning was necessary, 96% understood lens disinfection, and 99% expressed confidence in their ability to care for their lenses. PMID- 7796528 TI - Clinical experience with the SimulVue soft bifocal contact lens. AB - We fit the SimulVue bifocal contact lens, a soft lens with a simultaneous vision design, in 30 presbyopic patients. The lens has a central near correction surrounded by a concentric peripheral distance correction. Patients were evaluated prior to inclusion in the study and followed for a period of 1 year. The evaluation included visual acuity and contrast sensitivity at both distance and near with and without lenses. In addition, patients completed a questionnaire at the end of the study. At the end of 1 year, 16 of 30 (53%) patients were successfully wearing the contact lenses. Of these, 13 of 16 patients (81%) achieved J2 or better near vision, and 10 of 16 (63%) achieved 20/25 or better distance vision in both eyes. Greater reduction of contrast sensitivity occurred at near, with only 38% of patients (6/16) retaining their normal contrast sensitivity; whereas at distance, 81% of patients (13/16) retained normal contrast sensitivity. Fourteen patients failed to complete the study. The most common reasons cited were poor vision at distance (6/14, 43%), poor vision at near (6/14, 43%), and ghosting of images (4/14, 29%). We believe that the SimulVue contact lens is a viable option for the correction of many presbyopic patients. PMID- 7796527 TI - Gentle Touch, a lens material resistant to protein deposition. AB - We investigated the ability of the Gentle Touch, a non-ionic contact lens material containing 35% netrafilcon A and 65% water, to repel protein deposits. Studies were conducted in vivo (lenses worn by patients) and in vitro (lenses coated by artificial tears). Acuvue soft contact lenses, an ionic lens material containing 42% etafilcon A and 58% water, were used as controls. After 1 to 2 weeks of wear, protein deposits on Gentle Touch lenses averaged 1.5-2.8 micrograms per lens versus 338-444 micrograms per lens for Acuvue. Gentle Touch lenses that were heat-coated with an FDA tear solution recommended for testing protein deposition averaged 6.5 micrograms of protein deposits per lens, whereas almost 100 micrograms of protein was deposited on each Acuvue lens. Lenses treated with an artificial tear solution deposited a non-detectable amount of protein on each Gentle Touch lens versus more than 358 micrograms on each Acuvue lens. These studies demonstrated that Gentle Touch lenses are highly resistant to protein deposits. PMID- 7796529 TI - A comparative study of the microbiologic effectiveness of chemical disinfectants and peroxide-neutralizer systems. AB - We evaluated the antimicrobial activity of chemical and hydrogen peroxide neutralizer contact lens disinfection systems. The acute activity, storage, and recontamination potential of the two disinfection methods were compared by challenging the disinfectants with Staphylococcus spp., Pseudomonas aeruginosa, Serratia marcescens, Candida spp., and Aspergillus fumigatus. Chemical disinfectants preserved with polyquaternium-1 and polyhexamethylene biguanide and hydrogen peroxide-neutralizer systems with no additional preservatives were tested. Additionally, lens cases from patients using both systems were evaluated. Lens cases from patients using peroxide-neutralizer systems tended toward heavier contamination (31.8%) than the cases disinfected with a chemical system (20.3%, P = 0.16). The laboratory results showed that the differences in activity of chemical and peroxide-neutralizer systems was not statistically significant at the disinfection times against Staphylococcus epidermidis, S. marcescens, Candida parapsilosis, and A. fumigatus (P = 0.1037 to P = 0.5412). A statistical difference was shown against C. albicans (P = 0.0176) in favor of the peroxide neutralizer systems. The reverse was true during storage. Although the chemical disinfectants maintained the population of microorganisms, the bacteria and yeast increased to over 10(7) CFU/mL in neutralized peroxide systems. Overall, the results emphasize the importance of contact lens products containing preservatives for lasting protection from microorganisms. PMID- 7796530 TI - 8th International Congress of Mucosal Immunology. San Diego, California, July 17 20, 1995. Abstracts. PMID- 7796531 TI - Positive and negative feedback loops affect the transcription of IME1, a positive regulator of meiosis in Saccharomyces cerevisiae. AB - The IME1 gene of Saccharomyces cerevisiae encodes a transcription factor that is required for the expression of meiosis-specific genes. Like many of the genes it regulates, IME1 itself is expressed according to the following complex pattern: barely detectable levels during vegetative growth, and high induced levels under starvation conditions, followed by a subsequent decline in the course of meiosis. This report examines the influence of Ime1 protein on its own expression, demonstrating feedback regulation. Disruption of either IME1 or IME2 leads to constantly increasing levels of Ime1-lacZ expression, under meiotic conditions. This apparent negative regulation is due to cis elements in the IME1 upstream region, which confer transient meiotic expression to heterologous promoter-less genes. A specific DNA/protein complex, whose level is transiently increased under meiotic conditions, is detected on this element. In ime1- diploids, the level of this DNA/protein complex increases, without any decline. These results indicate that the transient expression of IME1 is apparently due to transcriptional regulation. This report also presents evidence suggesting that Ime1p is directly responsible for regulating its own transcription. Positive feedback regulation in mitotic conditions is suggested by the observation that overexpression of Ime1p leads to increased levels of IME1-lacZ. Negative autoregulation in meiotic cultures is demonstrated by the observation that a specific point mutation in IME1, ime1-3, permits expression of meiosis-specific genes, as well as induction of meiosis, but is defective in negative-feedback regulation of IME1. PMID- 7796533 TI - Developmental regulation of the ovine beta-lactoglobulin/human serum albumin transgene is distinct from that of the beta-lactoglobulin and the endogenous beta casein genes in the mammary gland of transgenic mice. AB - We compared the developmental pattern of expression of the sheep beta lactoglobulin (BLG), the chimeric BLG/human serum albumin (HSA), and the endogenous murine beta-casein genes in the mammary gland of virgin, pregnant and lactating transgenic mice, both at the RNA (expression) and protein (synthesis and secretion) levels. The BLG and casein genes were expressed at very low levels in virgin animals and during early stages of pregnancy. The increase in the expression of these genes started at the second half of pregnancy and reached a peak between the end of pregnancy and day 10 of lactation. The accumulation of their RNA coincided with that of the corresponding proteins, indicating a transcriptional control of expression of these genes. The expression and secretion patterns of the endogenous casein gene in transgenic and nontransgenic mice were indistinguishable. The hybrid BLG/HSA gene constructs displayed distinct patterns of expression in virgin animals and at early stage of pregnancy, from that of the BLG transgene or the endogenous mouse milk protein gene. High levels of expression (17-60% of that on day 18 of pregnancy) were detected in the mammary gland of virgin animals. At day 5 of pregnancy there was a dramatic decrease in HSA synthesis and secretion in all transgenic strains tested. The down-regulation, revealed by immunoprecipitation and immunohistochemical studies, demonstrated that at that stage of pregnancy only 10 18% of ductal structures contained HSA expressing cells in contrast to the majority of ducts expressing HSA in virgin animals. These morphological studies also demonstrated that the down-regulation in HSA synthesis and secretion was correlated with the transition from ducts comprised of a single layer of epithelial cells (characteristic of the virgin state) to ducts composed of multilayers of such cells. In two of the three transgenic strains tested, the down-regulation at the protein level was associated with a similar decrease in HSA transcripts. In the exceptional strain no. 23, HSA transcripts continued accumulating even at this stage. The differences in the control of expression at the RNA level between these transgenic strains were also confirmed by in situ hybridization. Our results suggest the involvement of at least two regulatory mechanisms effective at early stages of gestation in the control of expression/secretion of the HSA transgene targeted for expression in the mammary gland by the BLG milk protein promoter. These putative mechanisms may play key roles in the interplay between normal mammogenesis and lactogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7796534 TI - Developmental variability of metallothionein Mtn gene expression in the species of the Drosophila melanogaster subgroup. AB - Developmental expression of the Drosophila melanogaster metallothionein Mtn gene has been analysed. Transcripts of this gene accumulate during the vitellogenic phase of oogenesis in a ring of follicular cells at the oocyte-nurse cell margin and in the follicular cells surrounding the oocyte. There is also strong expression of the Mtn gene during the second half of embryogenesis in hemocytes, the endoderm midgut, and Malpighian tubules. A banded expression pattern is observed transiently in the midgut at stage 13. The two Mtn alleles, Mtn and Mtn, show quantitative differences in their expression patterns. Copper intoxication of flies does not induce ectopic expression of the Mtn gene, but rather leads to over-expression of the gene in the structures where it is normally transcribed. Mtn transcription is not altered in homozygous mutants of four genes (lab, wg, dpp, bap) known to be involved in midgut morphogenesis. Expression of Mtn has been also studied in six other species of the melanogaster subgroup. This analysis demonstrates that regulation of Mtn gene transcription has changed during evolution of the Drosophila lineage. For example, Mtn is expressed specifically in the Malpighian tubules of D. melanogaster, while in D. mauritiana and D. sechellia the amnioserosa is a specific location of expression. Nonetheless, expression of Mtn in the midgut is common to the seven species, suggesting a basic role for the MTN protein during embryogenesis in this organ, possibly in the release of metallic ions from vitellogenins. In contrast, two genes also expressed in the embryonic midgut, lab and dFRA, display identical patterns in all species of the melanogaster subgroup. The diversity of Mtn patterns in closely related Drosophila species exemplifies the rapid evolution of a gene regulatory system. PMID- 7796532 TI - Serum response element associated transcription factors in mouse embryos: serum response factor, YY1, and PEA3 factor. AB - Many mammalian transcription factors, including human and mouse serum response factors (SRFs), are post-translationally modified with O-linked N acetylglucosamine monosaccharides on multiple serine and/or threonine residues. Nuclear extracts were prepared from 9.5 to 19 days postcoitum mouse embryos and subsequently were fractionated by wheat germ agglutinin (WGA)-agarose affinity chromatography. SRF binds WGA-agarose and apparently is O-glycosylated. On the other hand, the low molecular weight serum response element (SRE)-binding proteins, including the previously named band I and band II factors, did not bind WGA-agarose. Furthermore, we showed that the fastest migrating complex contains the Yin-Yang 1 (YY1) factor. YY1 binds to the c-fos SRE and skeletal alpha-actin muscle regulatory element (MRE), but not the cardiac alpha-actin MRE. Nuclear extracts from NIH/3T3 fibroblasts contain similar, if not identical, SRE-binding complexes. Besides these SRE-binding factors, mouse PEA3-binding factor, presumably an ETS domain-containing protein, was found to bind SRF protein. This physical interaction, between SRF and ETS domain proteins, was shown to involve the DNA-binding domain-containing region of SRF and not the carboxyl-terminal transactivation domain. PMID- 7796535 TI - Genetic mosaic analysis of the equatorial-less mutation in Drosophila melanogaster. AB - eql (equatorial-less) is a recessive lethal mutation on the second chromosome of Drosophila melanogaster. J. Campos-Ortega found that eql clones in somatic mosaic flies have reduced numbers of photoreceptor cells, and he suggested that only the R1, R6, and R7 photoreceptor cells were missing in this mutant. These photoreceptor cells help to define the inverted orientation of ommatidial facets along the equatorial midline of the fly eye, hence the mutation was named "equatorial-less." We have conducted a detailed analysis of the eql mutation, by serial section reconstruction of eql clones marked with bw- or w- in somatic mosaic flies. We found that all photoreceptor cell types (R1-R8) could be deleted by the eql mutation, and in rare cases the number of photoreceptor cells was increased. The apparent lack of photoreceptor cell type specificity was confirmed by our analysis of genetically mosaic facets, which indicated that no single photoreceptor cell, or subset of photoreceptor cells, was uniquely required to express eql+. Rather, eql appears to function in all photoreceptor cells, and possibly in all eye precursor cells. The distribution of photoreceptor cell numbers in w eql facets was consistent with the hypothesis that each photoreceptor cell was deleted independently of the others. The eql gene is located on the right arm of chromosome 2 at map location 2-104.5 +/- 0.7 and lies between the polytene chromosome bands 59D8 and 60A7. PMID- 7796536 TI - Evaluation of an antisense RNA transgene for inhibiting growth hormone gene expression in transgenic rats. AB - We compared the levels of growth hormone (GH) mRNA in the pituitary, plasma GH concentration, and altered phenotype in rats heterozygous and homozygous for an antisense RNA transgene targeted to the rat GH gene, with those in nontransgenic rats. We initially investigated whether the transgene promoter, which is connected to four copies of a thyroid hormone response element (TRE) that increases promoter activity, affected in vivo transgene expression in the pituitary of the transgenic rats. Plasma GH concentration correlated negatively with T3 injection in surgically thyroidectomized heterozygous transgenic rats. There was a reduction of about approximately 35-40% in GH mRNA levels in the pituitary of homozygous animals compared with those in non-transgenic rats. Plasma GH concentration was significantly approximately 25-32 and approximately 29-41% lower in heterozygous and homozygous transgenic rats, respectively, compared with that in nontransgenic animals. Furthermore, the growth rates in homozygous transgenic rats were reduced by approximately 72-81 and approximately 51-70% compared with those of their heterozygous and nontransgenic littermates, respectively. The results of these studies suggested that the biological effect of GH in vivo is modulated dose-dependently by the antisense RNA transgene. The rat GH gene can therefore be targeted by antisense RNA produced from a transgene, as reflected in the protein and RNA levels. PMID- 7796537 TI - Embryonic regulation of histone ubiquitination in the sea urchin. AB - We have used quantitative 2-D protein electrophoresis and immunoprecipitation to study the patterns of histone ubiquitination at 10 h and 36 h of embryonic development in Strongylocentrotus purpuratus. Variants csH2A, alpha H2A, beta H2A, gamma H2A, delta HA, H2AF./Z, alpha H2B, beta H2B, and gamma H2B showed up to sevenfold differences in level of monoubiquitination between variants, and individual variants showed up to sixfold changes during development. At 36 h of embryogenesis, the late variants were less ubiquitinated than the early variants, although the overall level of ubiquitination was appreciably greater than at 10 h. Antiubiquitin antibodies were used to precipitate formaldehyde-fixed chromatin fragments in order to estimate the degree of ubiquitination of the early histone genes. The 5' regulatory region of the active H3 gene appeared to be at least twice as ubiquitinated as the adjacent upstream spacer. However, the absolute level of ubiquitination of the early histone gene repeat seemed to be independent of transcriptional activity. These results show that variant-specific ubiquitination of histones is a part of the developmental program in sea urchin embryos, but is not clearly correlated with transcriptional activity of the early histone genes, except perhaps in the regulatory regions. PMID- 7796538 TI - Antepartum fetal surveillance. PMID- 7796539 TI - The contraction stress test. AB - The CST is one of the first forms of fetal surveillance; it is still the only form that tries to use the principle of induced stress to reveal marginal placental insufficiency. With the expansion of biophysical evaluation, there are many choices in antenatal testing. Clearly the CST should not be the only form of testing to follow high-risk pregnancies. However, its proved efficacy and close correlation with intrapartum monitoring make it an essential tool. With nipple stimulation techniques, it is an easy and quick method for evaluating the fetus. Clinicians who follow high-risk pregnancies need to understand fully the administration and proper interpretation of the CST. PMID- 7796540 TI - Computerized analysis of the fetal heart rate. PMID- 7796541 TI - Computerized fetal biophysical assessment. PMID- 7796543 TI - Primary care in ob/gyn. PMID- 7796544 TI - Upper respiratory and pulmonary problems. PMID- 7796542 TI - Antenatal fetal assessment: overview and implications for neurologic injury and routine testing. PMID- 7796545 TI - Evaluation and treatment of uncomplicated hypertension. AB - The gynecologist is competent to perform an initial evaluation and workup on the patient with hypertension. The use of effective medications, such as the thiazides, beta-blockers, calcium-channel blockers, and angiotensin-converting enzyme inhibitors should control most patients. Patients with mild hypertension who have abnormal laboratory values or multiple other systemic diseases, or do not respond to therapy should be referred to an internist. Patients who present with markedly elevated systolic or diastolic pressure (e.g., a systolic reading higher than 160 mm Hg and a diastolic higher than 110 mm Hg) also should be referred to an internist for further evaluation. PMID- 7796546 TI - Common gastrointestinal syndromes diseases. AB - Gastrointestinal syndromes are an important contributory cause of morbidity for women, although in many cases, the gynecologist may primarily diagnose and treat uncomplicated disease. The role of endoscopy in the management of more difficult cases requires referral. The role of flexible sigmoidoscopy performed by the gynecologist for colorectal screening is intriguing. PMID- 7796549 TI - The role of the obstetrician/gynecologist in primary health care. PMID- 7796547 TI - Gallbladder disease and the gynecologist. AB - Gallbladder disease continues to be a common problem for women. Diagnostic tools such as ultrasonography have allowed earlier and more accurate diagnoses to be made. Therapies have changed significantly in the past few years, and the new treatments are associated with lower morbidity than is the classic cholecystectomy. The gynecologist should be aware of evolving technologies to assist his or her patient in choosing the safest and most cost-effective therapies. PMID- 7796548 TI - Headache. AB - An attempt has been made to provide an overview of headache management for the primary healthcare provider for women. No attempt has been made to delineate for the clinician all care related to the difficult-to-manage headache patient, but at the same time, information has been provided that should assist the clinician in treating this common disorder. Often, a comprehensive approach is needed, and appropriate referral may be necessary to other healthcare providers who are capable of providing more specific services. The women's healthcare provider often has important psychologic and environmental information necessary to provide meaningful early intervention. This common complaint in patients is often overlooked and/or dismissed as "happening to everybody," thus patients are unnecessarily neglected. Not only can specific therapy be provided for the headache patient, but this complaint can serve to alert caregivers to other organic and emotional problems. PMID- 7796551 TI - Nonstress test. PMID- 7796550 TI - Dynamic ultrasound-based fetal assessment: the fetal biophysical profile score. AB - The advent of ultrasound fetal imaging and the evolution of dynamic imaging (real time) methods have opened great new vistas in which fetal responses can be monitored with remarkable precision and clarity. Contained within this new wealth of information may lie the key to direct determination of the fetus at risk for death or injury in utero. Consideration of fetal activities so plainly recognized by conventional dynamic ultrasound methods and an assessment of fetal environment appear to be integral parts of this process. It is reasonable to assume that composite assessment by the dynamic ultrasound-based PBS will remain a valuable adjunct in caring for the high-risk fetus. PMID- 7796553 TI - Fetal movement monitoring. AB - Monitoring fetal movement serves as an indirect measure of central nervous system integrity and function. The coordination of whole-body movement, which requires complex neurologic control, is similar to that of the preterm newborn infant. Short-term observations of the fetus are best performed using real-time ultrasound imaging or Doppler ultrasound. Daily fetal movement charting by the compliant patient is a worthwhile adjunct in determining the frequency of fetal surveillance tests in the office and in predicting abnormal FHR patterns and perhaps impending stillbirth. Monitoring has its greatest value when placental insufficiency is long-standing, and its routine role in low-risk pregnancies requires further clinical investigation. The presence of a vigorous fetus is reassuring. Perceived inactivity requires reassessment of any underlying antepartum complication and more precise evaluation by FHR testing or real-time ultrasonography before delivery is considered. PMID- 7796552 TI - Fetal biophysical assessment in premature rupture of the membranes. PMID- 7796555 TI - Assessment of amniotic fluid volume in at-risk pregnancies. PMID- 7796554 TI - Vibroacoustic stimulation. AB - Vibroacoustic stimulation of the human fetus profoundly alters fetal behavior and heart rate. Many authors have reported success using this technique to improve the efficiency of antepartum fetal heart rate testing without changing the predictive reliability of the tests. Vibroacoustic stimulation has other potential advantages in the antepartum assessment of fetal well-being and in provoking fetal activity to improve ultrasonic visualization. From an experimental standpoint, vibroacoustic stimulation offers a unique opportunity to assess how the fetus responds to the external environment. The available information suggests that exposure of the fetus to vibroacoustic stimulation is clinically safe. Additional research is needed to characterize the optimal frequency, duration, intensity, and choice of stimulus to provide consistent responses. The literature presents a confusing array of studies using different methods, which makes comparison of results among institutions and investigators difficult. Vibroacoustic stimulation appears to be a reasonable and safe clinical technique. Additional prospective investigation is necessary to characterize further how this technique can be more useful clinically. PMID- 7796556 TI - Doppler ultrasound velocimetry for fetal surveillance. PMID- 7796557 TI - [The role of diuretics in antihypertensive therapy]. AB - Hypertensive therapy based on diuretics is time-honored. Thiazides represent the most commonly used class of diuretics for uncomplicated hypertension because of economic motivations, their tolerance and efficacy both as monotherapy and in combined treatment with other agents. Clinical studies using diuretics and beta blockers reported that thiazide treatment prevents the development of malignant hypertension, renal and heart failure, hypertensive retinopathy, and reduces in five years overall mortality of 33%, cardiovascular mortality of 41%, fatal and non-fatal cerebrovascular events of 51% and the risk of coronary events of 15%. The less than expected risk reduction of cardiovascular disease raised many concerns about the possibility of adverse biochemical changes of thiazides through their effects on lipids, electrolytes and glucose metabolism. However, the real clinical significance of these metabolic effects remains actually uncertain and needs further investigation. The treatment of the hypertensive patient cannot be adequately managed using a merely adjunctive step-care criterium. Hypertensive subjects have different haemodynamic, metabolic and endocrine disorders and a tailored treatment should consider the different activities of the various agents as monotherapy or in association in the single patient. PMID- 7796559 TI - [Gingival hyperplasia induced by amlodipine]. PMID- 7796560 TI - [Obesity and arterial hypertension. Relation between insulin secretion, peripheral insulin resistance and pressure indices]. AB - The association between obesity and hypertension has been well documented. Both conditions are often linked to an insulin resistance state. In a group of homogeneously obese hypertensive subjects, the presence of a significant correlation between degree of insulin resistance and severity of hypertension was found. These results confirm that, independently of obesity and insulin secretion, equally present in all the subjects, high blood pressure is inversely correlated to hormone sensitivity. PMID- 7796558 TI - [Evaluation of the action of glucomannan on metabolic parameters and on the sensation of satiation in overweight and obese patients]. AB - The authors studied the behavior of body weight, blood glucose, total serum cholesterol, and hunger and satiety sensation in 30 patients treated for 60 days with a 1.200 kcal (5040 kj) diet plus either placebo or glucomannane. All the variables considered show that the low-calorie diet plus glucomannane is more effective than the low-calorie diet alone. PMID- 7796561 TI - [The role of the endothelium of the microcirculation in the physiopathology of critical ischemia in the lower limbs as well as other forms of ischemic pathology]. AB - Critical ischemia of the lower limbs, the condition of decompensation of chronic obstructive arterial disease, is the upshot of a series of pathophysiologic events involving both the macrocirculatory and microcirculatory systems. It ist, however, the latter modulator of the decompensatory stage of arterial disease that conditions the severity and hence the anatomical and clinical pattern of ischemia. PMID- 7796563 TI - [Tumors of the temporal bone and the cerebellopontine angle. Diagnosis, characterization and assessment of extension by using imaging technics]. AB - We discuss in this paper the reliability of neuroimaging techniques in the diagnosis of neoplastic masses of the posterior-lateral skull base. We also discuss the role of TC and MRI in the evaluation of the extension pattern of these masses. PMID- 7796562 TI - [Orbital cellulitis in pediatric age. Report of a case and review of the literature]. AB - The authors report about 2-year-old female affected by orbital cellulitis. The most recent advances about physiopathology, diagnosis and therapy of orbital cellulitis are described. PMID- 7796564 TI - [Overdosing on diltiazem in heptic insufficiency]. AB - In a patient with hepatic failure of middle grade diltiazem at standard therapeutic dosis for unstable angina caused collateral fuss on atrioventricular conduction. This event is not considered in medical literature or on the schedule of the product. Because of the pharmacokinetics features of diltiazem, a higher risk of side effects can be expected if a abnormality of hepatic function is present. PMID- 7796565 TI - [Current orientation in medical management of ulcerative colitis]. AB - Authors synthetically remind epidemiology, eziopathogenesis and clinic of ulcerative colitis; they after describe the drugs employed in therapy of disease, stressing the mechanism of action, efficacy, collateral effects. Authors remember the choice of cortisonic therapy in the acute and severe periods of disease and the specific activity of salazopyrine and its metabolite 5-aminosalycilic acid in the ulcerative colitis and refer about the use of drugs as immunodepressors, fatty acids omega 3, zileuton, short chain fatty acids. Practical patterns of therapy in the diverse stages and clinical forms of the disease are exposed. PMID- 7796566 TI - [Tolerability and side effects of interferon alpha in the treatment of chronic viral hepatitis]. AB - It is reported a review on side effects and toxicity of alfa interferon in treatment of chronic viral hepatitis. The clinical experience in 44 patients affected by chronic hepatitis and treated with 3MU of alfa interferon is analysed. PMID- 7796568 TI - [Sarcoidosis with pulmonary abscess caused by emerging microorganisms]. AB - The association sarcoidosis-lung abscess due to emerging microorganisms-mycetoma has prompted the authors to report the above clinical case which is interesting in view of the rarity of the disease and of its infective complications. The authors also review the literature on the subject. PMID- 7796567 TI - [Retrospective study of 135 cases of lung neoplasms diagnosed between 1983 and 1993]. AB - The authors expose the results of a retrospective study concerning 135 cases of neoplasia diagnosed by their Department between 1983 and 1993. The patients' age, their sex, their consume of tobacco, their survival from the moment of the diagnosis have been considered in the study. Likewise the clinical instrumental researches and their reliability, the different incidence of the examined pathology in the first and in the second part of the period considered. It is emerged from the collected data, that also in our territory there is an increasing tendency in the incidence of lung neoplasia, a generally short survival after the diagnosis, a strong prevalence of smokers among those people affected from the disease, the difficulty of an early diagnosis due to scarce specificity of the commonest symptoms. The final auspicious is that a more incisive diligence in prevention and significant progresses in clinical pharmacological research may determine a notable reduction of the incidence of such a dramatic pathology. PMID- 7796570 TI - [Tumors of the sphenoid. Contribution of imaging technics with special reference to the role of magnetic resonance]. PMID- 7796569 TI - Prolonged treatment with ursodeoxycholic acid for primary biliary cirrhosis. AB - Eighteen patients affected with biopsy-proved primary biliary cirrhosis (PBC) (histological stage III and IV) received ursodeoxicholic acid (UDCA) 600 mg for 1 year. Signs and symptoms and biochemical tests (glutamic and oxalcetic transaminase, glutamic and pyruvic transaminase, bilirubine, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, bile acids, plasma proteins electrophoresis, immunoglubulins A, G and M) and antimitochondrial antibodies were evaluated before the treatment and every four months during the treatment. The results were compared with those obtained in 8 untreated patients affected PBC. The control group of patients were comparable (as far as age, histological stage, biochemical tests are concerned) to the group who received UDCA. Bilirubine, ALP, gamma-GT and LAP decreased during the treatment with UDCA and remained lower than baseline values until the end of the observation (12 months), while no changes occurred in the untreated patients. Both in the treated and untreated group plasma protein electrophoresis, serum immunoglubulins A, G and M remained unchanged, as well as anti-mitochondrial antibody. A moderate reduction of transaminases and bile acids was observed in the group of patients receiving UDCA but it did not reach statistical significance. In 16 out of the 18 treated patients pruritus disappeared and resulted diminished in the remaining 2 patients. No significant amelioration of pruritus was observed in the patients who did not receive UDCA. In conclusion, our data show that prolonged treatment with UDCA drastically reduces pruritus and improves cholestasis biochemical tests in patients affected with symptomatic PBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796571 TI - [A case of pulmonary aspergillosis effectively treated with itraconazole. Possible interaction of the antimycotic agent with hydroquinidine]. AB - This study describes a case of pulmonary aspergilloma in a neutropenic patient affected with myelodysplastic syndrome. It reports the therapeutic efficacy of itraconazole, emphasizing in particular the possible interaction with quinidine, with QT prolongation--at ECG--disappeared after quinidine withdrawal. PMID- 7796573 TI - Hidden assumptions in the critique of occult blood testing. PMID- 7796572 TI - Diagnosis and management of fulminant hepatic failure. AB - Fulminant hepatic failure is defined as the development of hepatic encephalopathy within 8 weeks of the onset of illness. While there are many causes of FHF, viral hepatitis, particularly hepatitis B, remains the most common etiology. Several drugs and toxins can also lead to FHF, most notably acetaminophen. Even with improvements in ICU care, mortality remains very high for these patients. Conservative management focuses on invasive monitoring and the prevention and treatment of complications like cerebral edema, infection, renal failure, and coagulopathy. Only orthotopic liver transplantation has reduced mortality from 80% to 30% to 50%. Therefore, the goals of management and treatment now include determining which patients are appropriate for liver transplant and finding a donor in a timely fashion. PMID- 7796575 TI - Transjugular intrahepatic portosystemic shunt (TIPS) in the management of esophageal variceal hemorrhage. PMID- 7796574 TI - Acquired immunodeficiency syndrome enteropathy: a perspective. PMID- 7796576 TI - Management of ascites. PMID- 7796577 TI - Extrahepatic manifestations of chronic viral hepatitis. PMID- 7796578 TI - A test of the association of a time-dependent state variable to survival. AB - An SAS macro which implements a more general version of the Mantel-Byar method is presented. Patients are assumed to potentially change between any number of states any number of times until censored or reaching a predefined endpoint. The macro employs methodology which generalizes that of the well-known logrank test to assess the association between state and endpoint. PMID- 7796579 TI - High performance computing for the human genome project. AB - Human Genome Analysis and Image Processing are part of the 'Grand Challenges' in High Performance Computing. The traditional mainframe has become insufficient for these applications in Biocomputing. New scalable parallel processor systems enter the marketplace with superior price/performance. The evaluation process of such a system by an application-oriented benchmark test suite is described. The system is integrated in the client/server structure of the Deutsches Krebsforschungszentrum where 'rightsizing' will eliminate the mainframe completely in the near future. PMID- 7796581 TI - Construction of molecular evolutionary phylogenetic trees from DNA sequences based on minimum complexity principle. AB - Ever since the discovery of a molecular clock, many methods have been developed to reconstruct the molecular evolutionary phylogenetic trees. In this paper, we deal with the problem from the viewpoint of an inductive inference and apply Rissanen's minimum description length principle to extract the minimum complexity phylogenetic tree. Our method describes the complexity of the molecular phylogenetic tree by three terms which are related to the tree topology, the sum of the branch lengths and the difference between the model and the data measured by logarithmic likelihood. Five mitochondrial DNA sequences, from the human, the common chimpanzee, the pygmy chimpanzee, the gorilla and the orangutan, are used for investigating the validity of this method. It is suggested that this method might be superior to the traditional method in that it still shows good accuracy even near the root of phylogenetic trees. PMID- 7796580 TI - Supercomputer algorithms for efficient linear octree encoding of three dimensional brain images. AB - We designed and implemented algorithms for three-dimensional (3-D) reconstruction of brain images from serial sections using two important supercomputer architectures, vector and parallel. These architectures were represented by the Cray YMP and Connection Machine CM-2, respectively. The programs operated on linear octree representations of the brain data sets, and achieved 500-800 times acceleration when compared with a conventional laboratory workstation. As the need for higher resolution data sets increases, supercomputer algorithms may offer a means of performing 3-D reconstruction well above current experimental limits. PMID- 7796582 TI - X-HUSAR, an X-based graphical interface for the analysis of genomic sequences. AB - Management and analysis of nucleotide and protein sequence and structure data constitute a traditional area of bioinformatics. Since the analytical programs are frequently developed by researchers, rather than software engineers, they tend to suffer from idiosyncratic and non-ergonomic man-machine interfaces. We report on HUSAR, our 140+ collection of third-party, as well as in-house developed or adapted, sequence manipulation and analysis tools, well integrated into the UNIX operating system environment and accessible via consistent menu aware interface. Most of the HUSAR programs can be completely specified by UNIX command-line options; they can thus be run in batches or combined into pipes. Adding such a program into the HUSAR environment is almost a 'plug-and-play' exercise. HUSAR has been recently complemented with a graphical client interface, X-HUSAR, to support users on UNIX platforms with X11 windowing systems. The whole X-HUSAR interface is based on a single generic program, COMLIGEN, and a number of specific configuration files. COMLIGEN interprets those files and renders appropriate windows, menus, and other interactive elements, which help the end user in selecting application programs and specifying their options. Efforts of extending both HUSAR and X-HUSAR are roughly linear to the size of the collection. PMID- 7796583 TI - SEQPWR and SEQOPR: computer programs for design of maximum information trials based on group sequential logrank tests. AB - The maximum information trial paradigm for clinical trials with failure time data was recognized and has been investigated. With the maximum information trial paradigm, a study is concluded when a prespecified maximum number of events of interest, thus maximum information, has been accrued if there was no early stopping due to treatment difference or lack thereof. We present two interactive FORTRAN programs for use in designing maximum information trials based on group sequential logrank tests. The program SEQPWR computes the attainable power of group sequential logrank tests given the combinations of the accrual and follow up durations. The program SEQOPR allows the users to investigate the operating characteristics of the maximum information trial given the information fractions of interim analyses. A clinical trial from the Eastern Cooperative Oncology Group is provided to illustrate the usage and features of the programs. PMID- 7796584 TI - A computer program linking physiologically based pharmacokinetic model with cancer risk assessment for breast-fed infants. AB - The risk assessment process predicts the chances of adverse health effects that the toxicant possibly can do to the target organism under expected conditions of exposure. Regulators chose among several mathematical approaches to estimate the risk, but in each case it is necessary to link the dosemetrics of the toxicant with its predicted health effect. In this paper, a computer program is described that allowed us to link a physiologically based pharmacokinetic (PBPK) model for tetrachloroethylene (PCE) in the lactating mother with the estimate of extra cancer risk for breast-fed infants, according to the U.S. Environmental Protection Agency (EPA) methodology. When inhaled by a lactating woman, PCE may partition into breast milk and may be transferred to the breast-fed infant. We have developed and validated experimentally a PBPK model for lactational transfer of PCE in rats, including a quantitative description of a milk compartment and the nursing pup. Subsequently, the model has been scaled to describe human physiology, and was validated with literature data for human cases of PCE exposure. Finally, we linked the dosage predictions of the PBPK model with equations used by EPA to estimate the cancer risk from PCE. The model predictions are in good agreement with both the measured values and those reported in the literature for exposure to PCE. This comparison confirms the usefulness of PBPK modeling in risk assessments. PMID- 7796585 TI - The pragmatics of clinical hypermedia: experiences from 5 years of participatory design in the MEDEA project. AB - To explore a medical hypermedia design process where requirements engineering and participatory design are used in a naturalistic setting, 5 years of participatory action research (PAR) have been performed in the development of a hypermedia system to be used in primary care practice. In PAR, the participating organizations cooperate with the researchers in deciding and later evaluating organizational actions, and the results are concluded cooperatively. A new type of system emerged from the study, in that the resulting design has its focus on the management of large volumes of hypermedia material, the traceability of authority in the documents, and teamwork support. Regarding the participatory design process, it was found to be essential to deal with social and organizational issues in the design group and its surroundings--and not to cover these over. For instance, an agreement was reached with the managers responsible for health care in the county where the design process took place, whereby the design activity was also given priority at the highest local administrative level. Since health care is a practice organization, there is a potential market for similar systems if only ways of organizing design and marketing the products of participatory design are further developed. Modified versions of structured product specification methods could be a valuable complement. The conclusion of the study is that the development and spread of hypermedia systems in health care may require considerable changes in current design routines and organizations. PMID- 7796586 TI - Bone mass and long-term monophasic oral contraceptive treatment in young women. AB - A prospective study has been designed to investigate bone metabolism in young women taking an oral monophasic contraceptive formulation (ethinylestradiol 20 micrograms + desogestrel 0.150 mg) over 5 years. Healthy women (n = 200) between 19 and 22 years of age were divided into two groups. Group A received oral contraception, Group B did not receive any treatment. All the subjects underwent a bone mass density (BMD) evaluation at spinal level L2-L4 with Dexa (Norland XR 26) and a measurement of the serum alkaline phosphatase levels and urinary excretion of OH-proline at baseline and every 12 months over 5 years. Our results demonstrated that Group A did not show any significant BMD change after 5 years of oral contraceptive treatment, while Group B demonstrated a significant increase (p < 0.01) in the bone mass content at the end of the time of observation (+7.8% after 5 years). No significant changes were found in serum alkaline phosphatase levels and in urinary excretion of OH-proline at the end of the study in comparison with basal levels in both groups. Our data suggested that long-term treatment with an oral monophasic contraceptive formulation (ethinylestradiol 20 micrograms + desogestrel 0.150 mg) did not modify the BMD but prevented the occurrence of the physiologic peak of bone mass in young women. PMID- 7796587 TI - Multicenter trial of two monophasic oral contraceptives containing 30 mcg ethinylestradiol and either desogestrel or gestodene in Thai women. AB - The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospective, open, group-comparative, randomized, multicenter trial of women asking for contraception. In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thailand, 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were randomly allocated to one of the two study groups. An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles. Criteria of cycle control, side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1, 3 and 6. Furthermore, the efficacy was evaluated after the last cycle. No pregnancies occurred with either of the contraceptives. The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle. Acne improved in both groups. Blood pressure and body weight remained unchanged. The two oral contraceptives were found to be effective and acceptable in Thai women. Compared to Caucasian women, the incidences of irregular bleeding and side effects were apparently lower in these Asian women. Furthermore, the effects of both oral contraceptives were comparable. PMID- 7796588 TI - Levonorgestrel intrauterine device in the treatment of menorrhagia in Chinese women: efficacy versus acceptability. AB - Ten Chinese women who had menorrhagia without organic cause and suffered from anaemia were treated with levonorgestrel intrauterine device for a total of 129 woman-months. There was a 54%, 87% and 95% reduction in menstrual blood loss at the first, third and sixth month of treatment when compared with the pretreatment cycle. These percentages of reduction were statistically significant, with p values of 0.004, 0.03 and 0.008, respectively. There was a median increase in menstrual cycle length of 12 days in nine months. Fifteen percent of the menstrual cycles were longer than 60 days. The total bleeding days increased by 4 days at the third menstrual cycles, but reduced to a median of 6 days at 6 months. Seventy-six percent of the menstrual bleeding was in the form of spotting. These Chinese women accepted such menstrual alterations. There was no hormonal side effects. All women preferred the device to hysterectomy. Levonorgestrel intrauterine device appeared to be an effective and acceptable treatment for menorrhagia in perimenopausal Chinese women. PMID- 7796590 TI - Endometrial morphometry in users of intrauterine contraceptive devices and women with ovulatory dysfunctional uterine bleeding: a comparison with normal endometrium. AB - Copper-bearing intrauterine contraceptive devices (IUCD) are commonly associated with menorrhagia. They cause certain morphological changes in the endometrium. These have been extensively reported and the mechanisms of menorrhagia have been investigated in a number of studies. By contrast, ovulatory dysfunctional uterine bleeding has not been as widely studied and mechanisms of menorrhagia in these patients are still not well understood. In this study, we examined endometrial morphometry in a group of women using IUCD, a group of women with ovulatory dysfunctional bleeding, and a control group of women with entirely normal cycles. There was increased leukocytic infiltration of the endometrium in both groups of women with menorrhagia compared to control cases. In addition, IUCD use was associated with greater luteal phase glandular epithelial height, supporting the concept of a secretory function defect in glandular epithelium. Possible links are postulated between static morphometric observations and dynamic biochemical changes. PMID- 7796589 TI - Return of fertility following discontinuation of Norplant-II subdermal implants. ICMR Task Force on Hormonal Contraception. AB - A total of 627 women who had discontinued the use of the Norplant-II implants for various reasons and were exposed to the risk of pregnancy were followed-up for two years for return of fertility. The cumulative conception rates in women who had discontinued due to planning pregnancy were 80.3 per 100 women at one year and 88.3 per 100 women at two years. The majority of women who did conceive (90 percent), had full-term normal live births; about 4 percent of women had spontaneous abortions, the remaining 6 percent decided on elective termination of pregnancy (ETP). The cumulative conception rates in women who discontinued due to bleeding irregularities and 'other reasons' were 64.5 and 55.8 per 100 women at one year and 77.9 and 75.1 per 100 women at two years, respectively. These rates were significantly lower as compared to those observed in women who discontinued due to planning pregnancy. A large proportion, about 40 percent, of women who conceived after discontinuation of the method due to bleeding irregularities and "other reasons," opted for ETP indicating that many women in these two groups did not desire another child and that such women need to be counselled for adopting another method of contraception. The spontaneous abortion rates observed in ex users of Norplant-II implants (1.7 to 4.4% pregnancies) were comparable to the spontaneous abortion rates prior to Norplant-II implant use (3.6% pregnancies) indicating that ex-users of Norplant-II implants were not at a higher risk of spontaneous abortion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796591 TI - Effects of mifepristone and progesterone on collagen synthesis in the human uterine cervix. AB - Antiprogestins are used to induce first trimester abortion and to dilate the cervix before vacuum aspiration. Cervical dilatation is associated with profound changes in the connective tissue. In what respect antiprogestins interfere with this process has hitherto been sparsely investigated. The aim of present study was to examine the influence of the antiprogestin mifepristone on cervical collagen synthesis in nonpregnant, early and late pregnant women. The effects were compared with those of progesterone. The content of collagen in cervical tissue was determined by measuring hydroxyproline. Collagen synthesis was studied in vitro either by incubation of cervical tissue specimens from women, pretreated with mifepristone in vivo, in the presence of 14C-proline or by incubation of cervical tissue of not pretreated women in the presence of the isotope and mifepristone or progesterone. Pretreatment with mifepristone, but not progesterone, induced a significant increase in cervical dilatation. The cervical concentration of collagen was not altered after mifepristone administration. Pretreatment with mifepristone did not quantitatively influence the time course of radiolabeling in vitro or the pattern of radiolabeling in different protein components as revealed by electrophoresis. In vitro mifepristone, like progesterone, reduced the incorporation of 14C-proline. From the present data we conclude that mifepristone pretreatment in connection with first trimester abortion is not associated with any major changes, qualitatively or quantitatively, of collagen synthesis. However, we cannot exclude that mifepristone still may affect the de novo formation of collagen since mifepristone, administered in vitro, did reduce collagen synthesis. PMID- 7796593 TI - The change of carnitine content in seminal plasma after reversible injection occlusion of vas deferens. AB - The change in carnitine content in seminal plasma after reversible injection occlusion of vas deferens (RIOVD) was observed. RIOVD is a safe, effective and simple method of male fertility control. Carnitine was determined by microenzymatic method. The incidence of sperm disappearance increased with the duration of RIOVD and reached 90% at the end of 12 months after operation. Before RIOVD, the mean value of carnitine in seminal plasma was 336.9 +/- 78.1 nmol/ml (X +/- SD, n = 58); after RIOVD, the mean value of seminal plasma carnitine was 112.7 +/- 50.7 nmol/ml (n = 172) in the group with sperm disappearance, and 172.5 +/- 71.7 nmol/ml (n = 51) in the group without sperm disappearance. There was a significant difference in carnitine content between pre-operation and postoperation (p < 0.01). After RIOVD, the carnitine concentration in seminal plasma of the group with sperm disappearance was lower than that of the group without sperm disappearance (p < 0.01). The results suggest that carnitine content in seminal plasma following RIOVD may be a reference index for judging the success or failure of the operation. PMID- 7796594 TI - Lactational anovulation in non-human primates: restriction of nursing inhibits Prl secretion without precipitating the return of ovulatory menstrual cyclicity in cynomolgus monkeys. AB - To test the hypotheses that nighttime suckling and elevated nocturnal prolactin concentrations are essential for the continuation of lactational anovulation, the effects of restricting nursing to twelve h per day (either day or night) on maternal prolactin (Prl) levels and resumption of ovulatory menstrual cycles were studied in five groups of cynomolgus monkeys: Group 1: baby weaned: Group 2: baby fully nursed: Group 3: baby nursed night only; Group 4: baby nursed day only; and Group 5: baby housed with mother but not allowed to nurse. Restrictions were initiated at approximately 150 days postpartum and were achieved by placing a non nursing jacket over the nursing jacket, which was worn 24 h/day. Fifteen out of seventeen monkeys remained anovulatory while housed with their infants, irrespective of the type of nursing restriction. First postpartum ovulations occurred approximately two months post-weaning. Plasma prolactin concentrations during both day and nighttime were significantly (p < 0.05) greater in the fully nursing group(s) than in all other groups. Fully nursing mothers had significantly (p < 0.01) greater prolactin concentrations at night than during the day. Among the restricted groups, the night only suckling group had significantly greater prolactin concentrations at night than the other restricted groups. There were no differences between daytime values, and within each restricted group there were no significant differences between day and night prolactin levels. We conclude that 1) nighttime suckling is not an absolute prerequisite for sustained lactational anovulation, and 2) suckling-induced hyperprolactinemia is not the principle mediator of lactational anovulation. PMID- 7796592 TI - The effect of small doses of progesterone released from two types of vaginal rings on ovarian activity and bleeding patterns during the first postpartum year. AB - A total of 20 breastfeeding women used progesterone-releasing vaginal rings for up to 12 months. The women were divided into two groups, one (n = 9) using rings with an initial release rate of 5 mg/24 h, the other (n = 11) with a release rate of 20 mg/24 h. Individual women started to give breast milk supplements and ceased to breastfeed after various periods of time. Urinary estrone and pregnanediol glucuronide levels were measured by radioimmunoassay three times weekly during the entire trial. Individual diary cards were used to register bleeding and spotting. A significantly higher concentration of pregnanediol glucuronide was seen when the 20 mg/24 h ring was used in the lactation period, in comparison with the 5 mg/24 h ring. In the post-lactation period, pregnanediol glucuronide levels dropped when the 20 mg/24 h ring was used. Estrone glucuronide levels increased after the termination of breastfeeding, indicating an enhanced suppression of ovarian activity in the lactation period with both rings. Although the degree of suppression was dose-related, both rings were likely to offer a sufficient contraceptive effect in the lactation period. No significant changes were observed when milk supplements were added to breastfeeding. The use of the 20 mg/24 h ring resulted in a much better bleeding pattern (significantly less bleeding days) than the 5 mg/24 h ring during the lactation period. In the post lactation period, the 20 mg/24 h ring the bleeding because much worse than in the lactation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796595 TI - Early abortifacient action of RU 486 by continuous intravenous infusion in rat. AB - RU 486 administered through constant intravenous infusion at 20 mg/kg dose on day 8 of pregnancy induced frank vaginal bleeding and resorption of all implantations in 100% rats. This was associated with an almost 4-fold reduction in progesterone secretion rate by the dispersed luteal cells ex-vivo. At 12 mg/kg dose, an incomplete resorption of implantations was observed in all treated animals. Results indicate that slow and continuous intravenous infusion of this antiprogestin was highly effective in terminating pregnancy shortly after implantation in the rat and this could, at least partially, be related to its luteolytic action in this species. PMID- 7796596 TI - A tribute to Christian Robert Klimt (1918-1994). PMID- 7796597 TI - Observational versus randomized medical device testing before and after market approval--the atherectomy-versus-angioplasty controversy. AB - Percutaneous transluminal coronary angioplasty was developed in the late 1970s as a nonsurgical alternative for revascularization of atherosclerotic coronary arteries. It gained widespread acceptance without a controlled trial. Introduced in 1986, directional coronary atherectomy was the first of other recently developed coronary devices that sought to improve on the results of angioplasty. It was approved in 1990 by the Food and Drug Administration (FDA) on the basis of observational data. Its use expanded rapidly, reaching over 35,000 procedures in 1992, accounting for more than 10% of all interventions. After premarket approval, two major randomized trials tested the hypothesis that atherectomy would be superior to angioplasty. Their results raised a cautionary flag and stood in contrast to projections made from prior observational data. It is concluded that randomized controlled trials validate claims of relative efficacy and safety of competing medical technologies, a lesson reflected in recent changes in policy at the FDA. PMID- 7796598 TI - A simple measure in defining optimal strata in clinical trials. AB - This paper deals with balancing groups with respect to prognostic factors in clinical trials, as a means of increasing the power of a study. We use the Mantel Haenszel statistic to obtain a simple measure for assessing the relative efficiency of different factors for stratification and to find optimal cutpoints for the given factors. For any available database, the measure can be used to construct optimal strata for a clinical trial. The paper also presents a practical approach for reducing the number of strata using discriminant regions with a method of assessing the effectiveness of this approach. An example from a large database of severe head trauma patients illustrates the utility of the measure. PMID- 7796599 TI - UKCCCR Register of U.K. Cancer Trials. AB - The UKCCCR Register of U.K. Cancer Trials comprises an on-line database of all randomized trials of cancer therapy, whether phase III or randomized phase II trials. Both current or open trials, and closed or completed trials, are included. Abstracts of any publications associated with the trials are also included. The UKCCCR Register is the initial component of a larger European register of trials. This article describes the structure and content of the database, the PC program for data entry, and the Unix-based browsing software for interactive access over networks. Problems of ensuring complete and comprehensive registration of trials, and sources of information, are also reviewed. PMID- 7796600 TI - The effect of topical retinoic acid (Etretinate) on mouse conjunctival Langerhans cells. AB - Four groups of BALB/c mice were treated locally with different concentrations (0.1-1.0%) of retinoic acid (Etretinate) ointment for a period of one to four weeks. A fifth group was treated with the ointment base only. Ia-positive dendritic cells were identified by an indirect immunofluorescence technique which was confirmed by ADPase staining. Quantitative counts of Langerhans cells were performed for each group. After four weeks, the 0.1 and 0.2% Etretinate-treated conjunctiva showed no significant reduction in Langerhans cell concentration. However, following 0.5 and 1.0% Etretinate treatment for four weeks, the concentration of Langerhans cells was significantly reduced, and the cells showed morphologic changes, consisting mainly of loss of dendritic processes. Between one and two weeks of therapy at these two high concentrations, no significant changes were found. Light microscopy of the conjunctival epithelium showed marked atrophic changes following four weeks of 0.5 and 1.0% Etretinate treatment compared to no changes with 0.1 and 0.2% Etretinate treatment. PMID- 7796601 TI - Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid. AB - Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant of retinal membranes whose deficiency causes retinal degeneration. Its antioxidant function is realized via scavenging peroxyl radicals as a result of which phenoxyl radicals of alpha-tocopherol are formed. Our hypothesis is that alpha-tocopherol phenoxyl radicals can be reduced by endogenous reductants in the retina, providing for alpha-tocopherol recycling. The results of this study demonstrate for the first time that: (i) endogenous ascorbate (vitamin C) in retinal homogenates and in rod outer segments is able to protect endogenous alpha tocopherol against oxidation induced by UV-irradiation by reducing the phenoxyl radical of alpha-tocopherol, (ii) in the absence of ascorbate, neither endogenous nor exogenously added glutathione (GSH) is efficient in protecting alpha tocopherol against oxidation; (iii) GSH does not substantially enhance the protective effect of ascorbate against alpha-tocopherol oxidation; (iv) exogenous dihydrolipoic acid (DHLA), although inefficient in direct reduction of the alpha tocopherol phenoxyl radical, is able to enhance the protective effect of ascorbate by regenerating it from dehydroascorbate. Thus, regeneration of alpha tocopherol from its phenoxyl radical can enhance its antioxidant effectiveness in the retina. The recycling of alpha-tocopherol opens new avenues for pharmacological approaches to enhance antioxidants of the retina. PMID- 7796603 TI - Co-transplantation of embryonic retina and retinal pigment epithelial cells to rabbit retina. AB - The retinal pigment epithelium (RPE) is important for normal development of the neural retina. We sought to investigate whether cografting RPE cells affected the differentiation and survival of retinal grafts. Pigmented embryonic day 16 (E16) rabbit retina was dissected either with or without attached RPE and injected into a lesion site in retinas of young adult rabbit hosts. Each host obtained a pure retina graft in one eye and a retina/RPE cograft in the other. Animals were sacrificed after 4, 8 and 12 weeks. After 4 weeks, grafts (1-2 mm in diameter) were seen in both experimental groups at the lesion site or in the subretinal space. However, 8 and 12 weeks after transplantation, the graft survival rate decreased. The grafts developed cell layers in folded sheets and many rosettes (a rosette consists of photoreceptors and cells of other retinal layers around a central lumen defined by an outer limiting membrane). Cografts of retina with RPE had areas of more distinct cell lamination than transplants of pure retina. Grafted RPE cells were organized in clusters of cells surrounded by extracellular matrix and often associated with blood vessels. If the extracellular matrix of RPE cell clusters was outside the rosettes close to inner retinal layers in the graft, transplant Muller cell endfeet developed an inner limiting membrane. Muller cell endfeet could also be observed in subretinal transplants attached to the denuded Bruch's membrane of the host. In 12-week grafts, when RPE cell clusters were inside rosettes, the surrounded photoreceptors survived better. No RPE effect could be seen if single RPE cells were dispersed among retinal donor cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796602 TI - Alteration of glutamine concentration in the vitreous humor in patients with proliferative vitreoretinopathy. AB - Using sensitive high performance liquid chromatography (HPLC), we measured free amino acid concentrations in the undiluted vitreous samples of patients who underwent pars plana vitrectomy for treatment of idiopathic preretinal macular fibrosis (PMF, n = 8), proliferative diabetic retinopathy (PDR, n = 12), or proliferative vitreoretinopathy (PVR, n = 15) to investigate the effect of vitreoretinal diseases on the concentrations of free amino acids in human vitreous. The most abundant amino acid was glutamine in all of three groups. Other major amino acids commonly found in the human vitreous samples were serine, alanine, arginine, valine, and lysine. Patients with PDR and PVR showed significantly lower concentrations of glutamine in vitreous (PDR: 655 +/- 230 nmoles/ml, PVR: 683 +/- 302 nmoles/ml) than those with PMF (PMF: 975 +/- 247 nmoles/ml; significance level, PDR: p < 0.01, PVR: p < 0.05). In addition, patients with grade D PVR showed significantly lower concentration of glutamine (357 +/- 117 nmoles/ml) than those with grade C PVR (802 +/- 256 nmoles/ml, p < 0.005), or PMF (p < 0.005). These results suggest two possible mechanisms for the alteration of intravitreal glutamine in the pathologic conditions. The first possibility is a reduced amount of supply of glutamine that is normally transported or released from surrounding tissues into vitreous humor. The second possibility is an increased amount of uptake and utilization of glutamine by cells within vitreous and pathologic tissues. PMID- 7796604 TI - The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and chromosome mapping. AB - We have isolated and characterized a human genomic clone containing the complete coding region of lens intrinsic membrane protein MP70 (Cx50). The coding region of this DNA is completely contained within one exon, as is common of all connexins investigated to date. The size of the Cx50 coding region, from the initiating ATG to the terminating TGA is 1,299 nucleotides, coding for a polypeptide of 432 amino acids and having a translated molecular weight of 48,171 daltons. This Cx50 coding region DNA was used as a probe to analyze a panel of Southern blots of human-Chinese hamster somatic cell hybrid DNAs to assign the gene coding for Cx50 to its human chromosome. Control human and Chinese hamster DNAs displayed a distinct Eco R1 restriction fragment pattern when hybridized with the human Cx50 DNA probe. When somatic cell hybrid DNAs were restricted with Eco R1 and Southern blots hybridized with the human Cx50 DNA probe, the characteristic human restriction pattern was observed only when human chromosome 1 was present in the hybrid panel. Of the other six connexin genes which have previously been assigned to a human chromosome, two of these, Cx37 and Cx40, are also found on chromosome 1. PMID- 7796606 TI - Effectiveness of specific antibiotic/steroid combinations for therapy of experimental Pseudomonas aeruginosa keratitis. AB - Ciprofloxacin and prednisolone, but not an aminoglycoside and dexamethasone, were previously found to be effective in killing bacteria and reducing inflammation for the treatment of Pseudomonas keratitis. We investigated the therapeutic effectiveness of tobramycin/prednisolone and ciprofloxacin/dexamethasone in a rabbit model of experimental keratitis to increase our understanding of the effectiveness of antibiotic/steroid combinations. To our knowledge, this is the first analysis of the effectiveness of a combination of ciprofloxacin and dexamethasone for experimental keratitis. Two experiments were conducted. In the first experiment, 36 rabbits were divided into six groups: 1) untreated; 2) prednisolone acetate, 1.0%; 3) prednisolone phosphate, 1.0%; 4) tobramycin, 1.36%; 5) tobramycin plus prednisolone acetate; 6) tobramycin plus prednisolone phosphate. In the second experiment, 23 rabbits were divided into four groups: 1) untreated; 2) ciprofloxacin, 0.3%, plus dexamethasone alcohol, 0.1%; 3) ciprofloxacin; 4) dexamethasone alcohol. Topical antibiotic and/or steroid was given for 10 h, from 16 to 26 h postinfection, one drop every 15 min for the first hour and then every 30 min for the remaining 9 h. At 27 h postinfection, eyes were evaluated by slit lamp examination (SLE) and assayed for the presence of bacteria in terms of colony forming units (CFU) per cornea. Both prednisolone acetate and prednisolone phosphate reduced ocular inflammation (as determined by SLE), compared with no treatment (P < or = 0.036); the phosphate was more effective (P = 0.005). Tobramycin alone and in combination with prednisolone also significantly reduced SLE, compared with no treatment (P < or = 0.006). The bactericidal activity of tobramycin was not affected by either steroid formulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796605 TI - A new fluorescent imaging procedure in vivo for evaluation of the retinal microcirculation in rats. AB - We investigated a new method for in vivo evaluation of the retinal microcirculation in rats using a cell-permeant fluorescent dye, acridine orange (AO), which stains cell nuclei and cytoplasm, and a scanning laser ophthalmoscope (SLO). AO, which binds and interacts with DNA and RNA, and thus stains cell nuclei and cytoplasm, was administered intravenously to rats. Fluorescein angiography was performed after administration of the AO, and fundus images were recorded on S-VHS videotape by means of an SLO. Argon laser was used as an exciter of the dye. The retinal vessels were stained with the dye, rendering the retinal microvasculature clearly visible. Cell nuclei and vessel walls were observed as greater fluorescence and lesser fluorescence, respectively. Leukocytes were also observed as highly fluorescent dots moving through the vessels. The results suggest that SLO visualization of AO uptake by cells may be a useful procedure for the evaluation of retinal microcirculation in vivo in rats. PMID- 7796608 TI - Molecular diagnostic tests for ascertainment of genotype at the rod cone dysplasia 1 (rcd1) locus in Irish setters. AB - Rod-cone dysplasia type 1 (rcd1) is one of several canine photoreceptor degenerations, collectively termed progressive retinal atrophy (PRA), that afflict different breeds of dogs. The rcd1 phenotype is an early onset autosomal recessive disease caused by a nonsense amber mutation, at codon 807, in the canine gene for the beta-subunit of rod cyclic GMP phosphodiesterase (canine PDEB). The mutation involves a G to A transition at nucleotide position 2420, which presumably would cause premature termination of the canine PDEB protein by 49 amino acid residues. In both a small pedigree study of Irish setters from the United Kingdom and in larger canine pedigree studies in the United States, this gene defect has been found to be the only mutation causing rcd1. Here we report development of a diagnostic test which unequivocally distinguishes the three genotypes at the rcd1 locus: rcd1/rcd1 (homozygous mutant, affected); rcd1/+ (heterozygous, carrier); and +/+ (homozygous normal, wildtype). PMID- 7796607 TI - Transforming growth factor-beta 1, -beta 2 and -beta 3 mRNA expression in human cornea. AB - The expression of TGF-beta 1, TGF-beta 2 and TGF-beta 3 precursors mRNA transcripts in in vivo human corneal cells were studied. Complementary DNA (cDNA) was generated from poly A+RNA extracted from in vivo human corneal epithelial cells, stromal keratocytes and endothelial cells. With the cDNAs as template, polymerase chain reaction (PCR) was carried out using specific primers of TGF beta 1, TGF-beta 2 and TGF-beta 3 precursors, synthesized by choosing specific nucleotide sequences in the latency-associated peptide region of each precursor. Southern blot analysis of the PCR products was carried out. In corneal epithelial cells, TGF-beta 2 mRNA transcript was strongly expressed; TGF-beta 1 and -beta 3 mRNA transcripts were also expressed; stromal keratocyte samples expressed TGF beta 1 and -beta 2 mRNA transcripts but not TGF-beta 3 mRNA transcript. Endothelial cells expressed all three transcripts. The present study, together with the authors' previous immunohistochemical study demonstrates that both protein and mRNA of TGF-beta 2-LAP are present in human corneal epithelium, indicating that TGF-beta 2 may play a crucial role in corneal epithelial cell layers. PMID- 7796609 TI - Direct access to dermatologic care is desirable. PMID- 7796611 TI - A dermatologic diary. Portrait of a practice. PMID- 7796612 TI - Miliaria. PMID- 7796610 TI - Consort contact dermatitis due to musk ambrette. PMID- 7796613 TI - Factitial panniculitis induced by cupping and acupuncture. PMID- 7796614 TI - Sweat gland carcinoma with metastases to the skin: response to 5-fluorouracil chemotherapy. AB - A 68-year-old white man presented to the inpatient service at Columbia Presbyterian Hospital with a chief complaint of a progressively enlarging tumor of the right infraorbital region for many years and multiple, pink papulonodules on his head, neck, and trunk. A biopsy specimen of the right infraorbital and back lesions demonstrated an infiltrating adenocarcinoma with prominent signet ring cells, and small lumen formation. Results of an extensive work-up revealed bone marrow metastases and no evidence of a primary malignancy. We present a case of primary sweat gland carcinoma with metastases to the skin based upon history, clinical presentation, results of physical examination, histopathologic examination, immunohistochemical studies, and response to 5-fluorouracil chemotherapy. Due to the rarity of the tumor, the diagnosis is usually not made until the tumor(s) is invasive. An excellent response to systemic chemotherapy with 5-fluorouracil in metastatic sweat gland carcinoma was noted in this case. PMID- 7796615 TI - Epidermotropic metastatic malignant melanoma. AB - Epidermotropic metastatic malignant melanoma can simulate a primary malignant melanoma. However, since therapeutic management can be drastically different for these two lesions, care must be taken in evaluating them. We report a woman with forty-eight metastatic lesions of malignant melanoma, twenty-two of which were removed and found on histologic examination to be epidermotropic metastatic malignant melanoma. PMID- 7796616 TI - Acrokeratosis paraneoplastica (Bazex syndrome) with oropharyngeal squamous cell carcinoma. AB - A 65-year-old white man presented with all the clinical features of acrokeratosis paraneoplastica of Bazex, characterized by violaceous erythema and scaling of the nose, aural helices, fingers, and toes, with keratoderma and severe nail dystrophy. Examination of the patient for possible associated malignancy disclosed an asymptomatic squamous cell carcinoma at the oropharyngeal region. The skin lesions resolved almost completely following radiation therapy of the neoplasm, but the onychodystrophy persisted. This case report illustrates the importance of early recognition of Bazex syndrome. PMID- 7796618 TI - Granulomatous glossitis as an unusual manifestation of Melkersson-Rosenthal syndrome. AB - The case of a 59-year-old man with granulomatous glossitis is presented. The patient complained of increasing swelling of his tongue for years and a recent onset of perioral edema. Because of sarcoid-like granulomas found in a first lingual biopsy specimen, the disease was initially misdiagnosed as a localized form of sarcoidosis. A second biopsy specimen from the tongue revealed lymphonodular-plasmocytic granuloma-like infiltrates, which, in connection with the labial swelling, led to the diagnosis of Schuermann's glossitis granulomatosa as a peculiar manifestation of Melkersson-Rosenthal syndrome. The surface of the tongue showed deep furrows characteristic of lingua plicata. However, no history or signs of facial or trigeminal nerve paralysis were present; thus the patient did not show the complete triad of symptoms typical of Melkersson-Rosenthal syndrome. After treatment with clofazimine the perioral and lingual swelling disappeared within two weeks. Recurrences have been suppressed with a reduced maintenance dosage of this agent. PMID- 7796617 TI - Deep dermatophyte infection with chronic draining nodules in an immunocompromised patient. AB - Chronic superficial dermatophyte infection may predispose the immunocompromised patient to invasive or disseminated involvement. We report a case of deep dermatophyte infection in a patient treated with long-term corticosteroid therapy for lung disease. The patient responded well to oral griseofulvin. Previously reported cases are reviewed along with recent investigative findings in the pathogenesis of chronic dermatophyte infections. Recommendations are made for diagnosis and therapy. PMID- 7796619 TI - Erythema multiforme associated with superficial fungal disease. AB - An extremely rare case of erythema multiforme associated with dermatophytosis by Trichophyton rubrum infection was reported in a 19-year-old woman. She had a reddish plaque resembling annular ringworm on her left arm. Treatment with an antifungal cream (clotrimazole) on the infected site cleared the condition in three weeks. Spontaneous regression of erythema multiforme in different parts of the body was recognized when the ringworm infection resolved. In recent years, only two cases have been reported in the English literature. PMID- 7796620 TI - The present and the future of higher medical education in China. PMID- 7796621 TI - Current status of rheumatic fever. PMID- 7796622 TI - Current means in the diagnosis and treatment of oral and maxillofacial tumors in China. PMID- 7796623 TI - Recent advances of otorhinolaryngology in China. PMID- 7796624 TI - LDL receptor research in China. PMID- 7796625 TI - Morphometric evaluation on myocardial protection of cold crystalloid versus warm blood cardioplegia. AB - Twenty patients undergoing open-heart valve replacement were divided randomly into two groups in this study; intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (hypothermic group) and continuous administration of warm blood cardioplegia with normothermic CPB (normothermic group) respectively. Tissue samples were taken from the right atrium before weaning from CPB and from the right appendage 30 minutes after removal of the cross-clamp. The results of pathological study in these two groups were as follows: the structural alterations were most severe during the ischemic period in the hypothermic group. Damages of the myocardial mitochondria examined with transmission electron microscope were found more severe in the hypothermic group than in the normothermic group, and in the reperfusion period than in the ischemic period. Loss of integrity of the mitochondrial membrane could be noted during reperfusion in the hypothermic group. The surface to volume ratios of mitochondria of each period of the two groups were calculated by computerizing the microphotographs of the myocardium. It was shown that the average of the surface to volume ratios was smallest in the reperfusion period in the normothermic group. It seemed that the volumes of the mitochondria were larger in the warm group than in the cold one. Probably the results were due to more severe damages of the mitochondrial membranes in the hypothermic group, which led to the release of the contents out of the mitochondria while in the normothermic group, the sodium-pump was disordered and it made the mitochondria swell. Pathologically, blood cardioplegic perfusion with the use of normothermic CPB is a feasible method for myocardial protection in open-heart surgery. PMID- 7796627 TI - Endolymphatic stromal myosis of the uterus. Clinicopathological analysis of five cases. AB - Five cases of endolymphatic stromal myosis (ELSM) were studied using histological, histochemical and immunohistochemical methods. ELSM is a well differentiated tumor resembling the normal endometrial stoma, with a low mitotic activity. So ELSM is considered as a kind of potentially malignant tumor different from endometrial stomal sarcoma and benign stromal nodules as well, though it can metastasize to the outside of uterus. ELSM may be derived from the stem cells that are normally present in the stroma of uterus, and can manifest multidifferentiation. PMID- 7796626 TI - Beneficial effects of NTG on left ventricular volumes and systolic function in patients with myocardial infarction. AB - The effect of sublingual administration and intravenous drip of nitroglycerin (SLNTG and IVNTG) on left ventricular volumes (LVVs) were studied and systolic function was quantitatively assessed with two-dimensional echocardiography (2DE) in 28 patients with myocardial infarction (MI), including 13 cases without heart failure (MI-NHF) in one group and 15 with heart failure (MI-HF) in another. The results showed that after SLNTG and IVNTG in both groups the heart rate (HR) increased significantly (P < 0.05-0.001); the systolic blood pressure (SBP) decreased significantly (P < 0.05-0.001); the diastolic blood pressure (DBP) was not significantly changed (all P > 0.05); the left ventricular end-diastolic and end-systolic volumes (EDV and ESV) both significantly reduced [EDV: decreased by 5.8-11.6% (-13.2-19.0 ml), P < 0.05-0.001; ESV: decreased by 9.6-16.6% (-8.6-17.3 ml), P < 0.05-0.001)]; the left ventricular ejection fraction (LVEF) all significantly elevated (increased by 6.6%-9.4% (3.2%-3.4%), P < 0.05-0.001] except in MI-NHF group after IVNTG; the segmental EF of normal and hypokinetic segments also significantly increased (P < 0.05-0.001). The results suggest that NTG could beneficially reduce left ventricular EDV and ESV; and improve or strengthen its global and segmental systolic function in MI patients, particularly noticeable in patients with heart failure. PMID- 7796628 TI - Factors related to long-term effects of thymectomy on myasthenia gravis. AB - The authors report the results of long-term follow-up after thymectomy on 92 cases with myasthenia gravis (MG), including 22 cases of thymomatous MG. These patients were followed up for 6-73 months with an average of 23 months. The surgically effective rate was 88.0% and the late mortality, 6.5%. The sex of the patients and the durations of disease were not obviously related to the prognosis, however the effect of thymectomy was much better in patients aged 10 39 years than in other age groups. The modified Osserman's clinical classification, acetylcholine receptor (AchR) antibodies and citric acid extract (CAE) antibodies titers in plasma and pathological patterns of the surgical specimens of thymus including immunohistochemical observation play an important role among various factors related to the long-term effects. PMID- 7796630 TI - Value of polymerase chain reaction assay in diagnosis of intestinal tuberculosis and differentiation from Crohn's disease. AB - It is difficult to make a precise diagnosis of intestinal tuberculosis and to differentiate it from Crohn's disease. For evaluating Polymerase Chain Reaction (PCR) assay in these two aspects, 36 specimens of intestinal tuberculosis from surgical resections and endoscopic biopsies and 26 Crohn's disease samples were subjected to PCR assay. 21 specimens of normal colon tissue surrounding cancer were used as the control. Oligonucleotides derived from the IS 6110 sequence, which is repeated in M. tuberculosis chromosome and highly specific for the M. tuberculosis complex, were used as a primer. The amplified PCR products were detected by examination of ethidium-bromide-stained polyacrylamide gels. The specificity of PCR products was confirmed by digestion with Sal I restrictive endonuclease and southern blot hybridization using digoxigenin-labeled probe. The results showed that the M. tuberculosis DNA was identified in 27/36 intestinal tuberculosis, but none of 26 Crohn's disease. Acid fast bacilli were only found in 16/36 intestinal tuberculosis. In conclusion, as a rapid, sensitive, and specific pathogenic method in diagnosis of intestinal tuberculosis, PCR assay has been developed in this study, and is considered valuable in the differentiation between intestinal tuberculosis and Crohn's disease. PMID- 7796629 TI - Clinical value of urinary and serum pseudouridine in diagnosis and monitoring of primary liver cancer. AB - Urinary and serum pseudouridine concentrations were determined by high performance liquid chromatography in 80 patients with primary liver cancer, 32 with benign space occupying lesions of the liver, 42 with liver cirrhosis and 40 healthy subjects. Their mean urinary and serum pseudouridine levels were 39.2 +/- 11.5 nmol/mumol creatinine and 3.4 +/- 1.3 mumol/L, 24.5 +/- 5.4 nmol/mumol creatinine and 2.5 +/- 0.5 mumol/L, 22.8 +/- 7.8 nmol/mumol creatinine and 2.3 +/ 0.4 mumol/L, 26.4 +/- 4.6 nmol/mumol creatinine and 2.3 +/- 0.4 mumol/L, respectively. Exceeding the mean plus 2SD of pseudouridine of healthy control was considered as positive value for the diagnosis of primary liver cancer. Thus the positivity of urinary and serum pseudouridine in hepatoma was 71.3% and 70.0%, respectively. The positive rate of combined pseudouridine and alpha-fetoprotein assay was 91.3% in patients with hepatoma. Besides, pseudouridine levels could elevate before positive localization and reduce to normal levels after tumor resection. The results showed that the determination of pseudouridine is of clinical significance in the diagnosis and monitoring of primary liver cancer. PMID- 7796631 TI - Neuron-specific enolase in patients with acute ischemic stroke and related dementia. AB - Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in acute ischemic stroke patients as compared with the controls. The altered CSF NSE levels correlated well with the infarct size in CT scan. The CSF NSE levels were higher in 6-multiinfarct dementia (MID) patients who were diagnosed after 6-month follow-up than those in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE in the study of dementia related to ischemic stroke is worth further studies. PMID- 7796632 TI - The biological function of retinoblastoma gene. PMID- 7796633 TI - Abstracts from the first annual conference of the Chinese Society of Medicine in Germany. PMID- 7796634 TI - Responses of respiratory-modulated facial nerve activity to activation of the ventrolateral subarea of the nucleus of the tractus solitarius. AB - The purpose of the present study was to examine respiratory-modulated facial nerve activity (FNA) in response to activation of the ventrolateral subarea of the nucleus of the tractus solitarius (vlNTS). The cat was anesthetized with sodium pentobarbital and then vagotomized bilaterally, paralyzed and ventilated artificially. End-tidal fractional concentration of CO2 was maintained at hyperoxic normocapnia. Partial occipital craniotomy was performed to expose the obex. Activities of the phrenic and the facial nerves were simultaneously recorded. The vlNTS was excited by electrical current (80 Hz frequency, 0.5 ms pulse duration and a variety of current from 12.5 to 50 microA) and glutamate (30 100 nl, 0.5 M). Three responsive patterns for both nerves were observed in response to vlNTS activation. First, inspiratory facial nerve activity (iFNA) and phrenic nerve activity (PNA) were decreased (p < 0.01), while expiratory facial nerve activity (eFNA) was not changed. Second, iFNA and PNA were diminished (p < 0.01) but eFNA was enhanced. Third, iFNA was decreased whereas PNA was enhanced. These results suggest that there might be a neural pathway projecting from the vlNTS to the facial nuclei to modulate respiratory-modulated facial nerve activities. PMID- 7796635 TI - Surface temperature change, cortical evoked potential and pain behavior elicited by CO2 lasers. AB - The performance of a self-designed CO2 laser stimulator, TL#2, was evaluated against a commercial product, model DE20XL of the Direct Energy Inc. (Irvine). The major items evaluated were the temperature change of the irradiated surface and the electrophysiological and behavior changes in the rat elicited by single laser pulse irradiation. Single shots of TL#2 produced a profile of surface temperature change similar to those of the DE20XL, as quantified by their maximal temperature change, rate of rise (half time to maximum) and rate of temperature drop. TL#2 and DE20XL elicited the same pain behaviors and the same pattern of cortical evoked potential in awake, behaving rats. TL#2 differed from the DE20XL in its laser beam shape and focal depth. The cross sectional energy profile of the TL#2 was a Gaussian shape, i.e., most intense at its center point, whereas that of the DE20XL with the FL20XL attachment had a shape of an inverted Gaussian, i.e., most intense in the periphery. Consequently, the peak energy of the center of the TL#2 laser beam grows rapidly with an increase in the pulse intensity. Caution must be taken not to use this machine at high intensity or for long duration less permanent damage should be produced on tested animal or human subject. In summary, TL#2 when used properly, should be a useful tool in the study of pain mechanism. PMID- 7796636 TI - Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze. AB - This study investigated the roles of hippocampal N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptors in acquisition, consolidation and retrieval processes of spatial memory. Male Wistar rats with indwelling cannulae in the dorsal hippocampus received 4 training trials on the Morris water maze for consecutively 6 days. Rats received infusion of the NMDA receptor antagonist 2-amino-5 phosphonopentanoic acid (AP5) or the AMPA receptor antagonist 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX) into the hippocampus under one of the three schedules: 5 min prior to each daily training session, immediately after each daily training session or 5 min prior to the final testing trial. Pretraining intra-hippocampal infusion of 5.0 micrograms AP5 retarded acquisition. The same dose of AP5 given after training had little effect but a higher dose (10.0 micrograms) did slow down progress in the acquisition curve. Pretest infusion AP5 failed to affect memory retrieval. Pretraining intra-hippocampal infusion of 1.0 micrograms CNQX also impaired acquisition, but posttraining infusion of CNQX at 1.0 or 2.0 micrograms had no effect. However, pretest infusion of 1.0 micrograms CNQX markedly impaired retrieval of the already-formed spatial memory. These findings taken together suggest that acquisition in a spatial task involves hippocampal NMDA and AMPA receptors, consolidation of spatial memory involves NMDA receptors and retrieving such memory involves AMPA receptors. PMID- 7796637 TI - Betel quid chewing damaged gastric mucosa: protective effects of cimetidine and sodium bicarbonate. AB - The effects of cimetidine and NaHCO3 on gastric acid back-diffusion (either the H+ loss or the Na+, K+ and CA++ gain in the gastric lumen) and mucosal ulceration were studied in rats with chronic feeding of betel quid chewing (BQC)- or its individual component-containing food. After 30 and 90 days of feeding, the animal was fasted for 24 hrs and vagotomized. An acid solution (100 mM HCl plus 54 mM NaCl) with or without drugs was irrigated in the rat stomach for 3 hrs. The results indicated that BQC and its individual component produced a variety of change in enhancement in acid solution-induced acid back-diffusion and mucosal hemorrhagic ulceration but in decrease of gastric mucus secretion. These parameters were dose-dependently reversed by intragastric cimetidine (50-300 mg/kg) in BQC-treated rats. Similar but lesser effect than cimetidine (300 mg/kg) was obtained by intragastric administration of NaHCO3 (52 mg/kg). It is concluded that in BQC- or its component-feeding rats, the enhancement in acid back diffusion and the reduction in mucus secretion are at least in part responsible for the formation of hemorrhagic ulceration which can be inhibited by intragastric cimetidine or NaHCO3. PMID- 7796638 TI - The influence of body size to the parameters of gastric slow wave: studied with an assembled electrogastrography. AB - An electrogastrographic (EGG) device has been assembled, it consisted of the following main components: amplifiers, band-pass filter, analog/digital converter, low band-pass digital filters which could pick up signals between 0.02 Hz (1.2 cpm) and 0.1 Hz (6 cpm), and a personal computer. The analysis softwares employed autoregressive moving average modelling to compute frequency of slow wave, and overlapping Welch periodogram of fast Fourier transform for power computation. In order to study the influence of body size to the EGG parameters, 28 healthy males (age: 18-45 years) without any gastric dysmotor disorders were enrolled to record fasting EGG. Another 28 age-matched females were enrolled to record and to compare the EGG parameters. Of the EGG frequencies, both males and females were approximate to 0.05 Hz (NS). However, the EGG power values were markedly different between the male and female measurements (Mean +/- SD: 57.3 +/ 16.6 dB vs. 46.8 +/- 14.7 dB, p < 0.01). Correction with body mass index eliminated this difference. Of all measured EGG power values, a positive correlation with body mass index was seen (r = 0.39, p < 0.005). We conclude that a different EGG power value exists between the male and female subjects, body size is probable an important factor to elicit this difference. PMID- 7796639 TI - Radial asymmetry characterized the upper esophageal sphincter pressures. AB - The characteristics of the upper esophageal sphincter (UES) motor functions remain unknown in Chinese. Twenty-three volunteers (M/F: 10/13, age: 19-40) without any pharyngeal/esophageal motor disturbance underwent UES measurement in the left decubitus position using a low compliance pneumohydraulic infusion system. These measurements included the location of UES from nostril, its resting pressure, and the responses to swallow. Mean UES resting pressures measured with three 120 degrees oriented manometric orifices were 22.6 +/- 7.7 mmHg, 16.9 +/- 8.6 mm Hg and 20.7 +/- 9.6 mmHg respectively (p < 0.05). In regard with the swallow-induced UES relax ability, the relax interval, the post-relax contractile amplitude and interval, neither dry swallow nor wet swallow led to a different result. Mean measured UES location from the nostril with the most proximal orifice of probe was 29.3 +/- 2.3 cm. This location did correlate very well with body height (r = 0.60, p < 0.01). In conclusion, this study demonstrates that the UES resting pressures exhibit a radial asymmetry, and that the type of swallow does not influence UES responses. Furthermore, an equation based on the body height may predict the most appropriate UES position. PMID- 7796640 TI - Age-related difference in the in vitro response of erythropoietin to triiodothyronine in male rats. AB - The effect of aging on medium erythropoietin (EPO) levels after triiodothyronine (T3, 1 nM) stimulation in vitro and on the EPO content of kidney extract were investigated. Middle (mid)-aged (17 months), adult (6 months) and young (3 months) male rats were decapitated. The kidneys were decapsulated and cut into 6 equal pieces. One sixth of the kidney was extracted by phosphate buffer before measuring the content of EPO in kidney and one sixth of the kidney was incubated in vitro with T3 (1 nM) at 37 degrees C for 30 min. The concentration of EPO in both medium and kidney extract was measured by a radioimmunoassay (RIA). The EPO content in kidney was higher (p < 0.05) in the mid-aged than in the young rats. The basal level of medium EPO was not changed by age. Only young rather than adult or mid-aged rats showed an increase of EPO secretion after T3 stimulation (p < 0.01). These data suggest that the EPO concentration in rat kidney and the action of T3 on EPO release from the kidney are age-dependent. PMID- 7796642 TI - [Mosaicism confined to placenta in pregnancies with adverse outcome]. AB - Chorionic villi and fetal tissues from 50 pathological human conceptions at gestational weeks 9-40 were cultured and cytogenetically analyzed to explore the existence of chromosomal mosaicism confined to the extraembryonic tissues and to clarify the relationship between confined placental mosaicism and adverse outcome of pregnancy. Chorionic villi and fetal tissues from 12 second trimester gestations terminated served as a control group. In two pathological gestations true mosaicism was found exclusively in chorionic cells and could not be confirmed in cells derived from the fetal tissues. One of these was severely growth retarded. Concordant results were obtained in all other cases. PMID- 7796641 TI - Effects of age on open-field behavior of male rats. AB - As age advances, the performance of animal behavior declines gradually. The purpose of this study was to investigate the onset of age-related changes in open field behavior of rats from a wide age spectrum. Male Long-Evans rats, ranging from 2 to 22 months, were placed in an open-field apparatus during the dark phase for a cumulative period of 28 min. Data were collected for the following parameters of open-field behavior: horizontal activity (HA), total distance (TD), stereotypy count (SC), vertical activity (VA), movement time (MT) and margin time (MGT). The highest value of HA, TD, SC and MT was found in rats at the age of 3 months. After 3 months, the values for these parameters gradually declined, subsequently reaching statistical significance by 6 months (HA, TD and SC) or 8.5 months (MT) of age. Maximum activity of VA occurred at 8.5 months of age and thereafter gradually declined with increasing age, however, no significantly statistical difference was reached as compared to the highest value. In contrast, the values for MGT gradually declined after 2 months of age, thereby reaching statistical significance by 11 months of age. These results indicate that the onset of age-related decline in open-field behavioral parameters can differ and the age-related changes in open-field behavior depends on observational parameters. PMID- 7796643 TI - [The effects of progestin on the bone metabolism in postmenopausal women]. AB - Thirty postmenopausal women, including 26 with history of hysterectomy and bilateral salpingooophorectomy due to uterine myoma and 4 with natural menopause without any diseases were randomly allocated into two groups. Fifteen subjects received medroxyprogesterone acetate (MPA) 10 mg twice daily for three months, the other 15 received both MPA 10 mg twice daily and cyclopentylethinyl estriol (CEE3) 5 mg once a month for three months. Fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHpr/Cr) ratio, serum calcitonon (CT) and alkaline phosphatase (AKP) concentrations were measured before and after treatment in all subjects. The results showed that in both groups, the fasting urinary Ca/Cr and OHpr/Cr ratio reduced significantly, while serum CT and AKP increased significantly after treatment. The changes of these parameters were not significantly different between these two groups. These data indicated that progestin alone appeared effective in preventing postmenopausal osteoporosis. PMID- 7796644 TI - [Laparoscopic treatment of endometriosis with Nd: YAG laser and microwave]. AB - A series of 200 cases of endometriosis were treated laparoscopically by Nd: YAG laser and microwave at Peking Union Medical College Hospital. All the operations were performed under local and topical anesthesia follow-up for 10-48 months revealed good results. Of 76 cases with infertility, 46 (60.5%) conceived after treatment. Of 114 cases with ovarian endometriomas, the cysts were no longer found in 81 cases (71.1%), decreased in size in 24 cases (21.0%). Of 180 cases with pain symptoms, 105 patients (58.3%) were achieved complete relief, Partial relief in 61 cases (33.9%). It has been found that laparoscopic surgery is effective to improve fertile rate for the patients with all the stages of endometriosis. The results showed that the microwave and Nd: YAG laser can be achieved with safety and success. The microwave is safer than Nd: YAG laser and is easier to operate and less expensive. PMID- 7796645 TI - [Study on chromosomal centromeric dots in couples with spontaneous abortion]. AB - Chromosomal centromeric dots (Cd) of peripheral blood in 20 couples with spontaneous abortion and 10 normal couples were studied by Cd-banding technique. The frequencies of Cd loss and centromeric dots-nucleolar organizer region (Cd NOR) fusion were 0.36 +/- 0.15/cell and 0.31 +/- 0.20/cell in the couples with abortion, 0.22 +/- 0.13/cell and 0.20 +/- 0.19/cell in normal couples respectively. These results showed that frequencies of Cd loss and Cd-NOR fusion in couples of spontaneous abortion were significantly higher than those in the normal couples. We suggested that the occurrence of spontaneous abortion in human might casually relate to the changes of Cd. PMID- 7796646 TI - [Fecundify after treatment of tubal pregnancy]. AB - This study is a follow-up analysis of 103 patients who desired to preserve their fertile ability after treatment of tubal pregnancy. Among the 103 cases, 58 were treated by unilateral salpingectomy, 15 by salpingostomy and 30 by drug conservative therapy. RESULTS: 67 cases had intrauterine pregnancy and 9 cases repeated ectopic pregnancy. The intrauterine pregnancy rate of the surgical group (71.2%) was higher than that of the nonsurgical group (50.0%). And the pregnancy rate of salpingostomy group (86.7%) was higher than that of salpingectomy group (67.2%). No repeated ectopic pregnancy occurred in the salpingostomy group. After three months of treatment, 45 cases were randomly sampled for tubal patency test. Bilateral tubal patency rate in salpingostomy group was 93.3% and in drug treatment group was 20.0%. These results indicated that tubal patency is an essential factor for normal pregnancy. Prevention of post-operative adhesion and treatment of pelvic inflammatory disease are important for increasing intrauterine pregnancy rate and decreasing repeated ectopic pregnancy rate. PMID- 7796647 TI - [Chemotherapy against lymphatic metastases of gynecologic cancer via pelvic retroperitoneal cannulation: a preliminary report]. AB - Lymphatic metastasis is one of the most important problems in the treatment of gynecologic malignancy. We conducted a preliminary investigation on the feasibility and practicality of chemotherapy against lymphatic metastases of gynecologic cancer via pelvic retroperitoneal cannulation. 5-FU mixed with Isovist-300 was injected into the pelvic retroperitoneal space. X-ray films revealed that the external iliac, hypogastric, obturator, deep inguinal and most of the common iliac lymph nodes were submerged in the 5-FU solution. 5-FU concentrations in the lymph nodes were measured by high pressure liquid chromatography, which showed that 5-FU concentration of the study group was 2 to 10 times that of the control group. Pathologic findings revealed that most of the metastatic cancer cells in the study group showed obvious degeneration and necrosis while no changes were observed in the control group. No major complications or adverse effects were observed. Our results suggest that this method may be used to treat the lymphatic metastases of gynecologic cancer. PMID- 7796648 TI - [Overexpression of p53 in transitional cell carcinoma of the ovary]. AB - To determine the prevalence of p53 abnormal protein expression in transitional cell carcinoma of the ovary in Peking Union Medical College hospital, and to analyse the correlation between the overexpression of p53 protein and prognostic parameters of transitional cell carcinoma of the ovary, thirty-two transitional cell carcinoma of the ovary and 20 normal ovaries were analysed. Detection of overexpression of p53 protein was carried out by immunohistochemical staining (IHS) using the monoclonal antibody DO-1 on paraffin sections. 41% of 32 samples of transitional cell carcinoma of the ovary showed positive IHS with DO-1, whereas only 5% of 20 normal ovaries showed weakly positive cytoplasmic staining (P < 0.01). p53 overexpression did not correlate with age, CA125 levels, histological grade and lymph node metastasis, but patients with overexpression of p53 had a poor prognosis. Overexpression of p53 is a more common event in transitional cell carcinoma of the ovary. Further studies are warranted to clarify the role of p53 in transitional cell carcinoma of the ovary. PMID- 7796649 TI - [The analysis of tumor growth rate and histopathology of xenografts of nude mice bearing human ovarian carcinoma in immunocompetent mice]. AB - Xenografts of nude mice bearing human ovarian carcinoma cell line SKOV3 were transplanted using subrenal capsule assay (SRCA) in immunocompetent C57BL/6 mice. Multiple locations were chosen on both sides of the kidneys obtaining a total of 129 tumors. The volumes of the tumors were measured and histopathological examinations were conducted on the 4th, 6th, 8th, 10th, 12th and 14th days after transplantation surgery. The growth rates were noticed to be high on the 6-8th days. Lymphocytic infiltration reached a peak on the 8-12th day. On the 14th days the leukocytic infiltration and fibrosis almost surrounded the tumors. Tumor cells that could be found amounted to about 77.25%, 65.38%, and 52.17% respectively on the 4th, 6th and 8th days, but significantly decreased on 12-14th days. The above results suggested: (1) multiple SRCA on both sides proved to be practical and economical; (2) the xenografts of nude mice bearing hman ovarian carcinoma could be transplanted viably by SRCA for 8-10 days; (3) microscopic measurements of the transplanted tumor volume did not represent the real status of the tumor growth, and microscopic evaluation was necessary. PMID- 7796650 TI - [A research on serum, urine and tumor tissue hyaluronate assays for detecting malignant ovarian tumors]. AB - Hyaluronate contents were determined by radioimmunoassay in 91 samples of serum, 88 samples of urine and 32 samples of ovarian tumor tissue from patients with benign and malignant tumors and from healthy subjects. The mean serum hyaluronate level in patients with malignant ovarian tumors (mean, 155.99 micrograms/L, range, 20 to 680 micrograms/L) was significantly higher than that in patients with benign ovarian tumors (mean, 84.2 micrograms/L; range, 20 to 188 micrograms/L) and that in healthy subjects (mean, 57 micrograms/L; range, 2 to 110 micrograms/L). The mean urine hyaluronate level in the malignant group (mean, 307.83 micrograms/L; range 50 to 750 micrograms/L) also was significantly higher than that in the normal control group (mean, 146 micrograms/L; range, 40 to 242 micrograms/L). The results suggest that serum and urine hyaluronate determination in the detection of malignant ovarian tumors is of clinical value. PMID- 7796651 TI - [Perinatal asphyxia]. PMID- 7796652 TI - [Advances in the research of neu proto-oncogene in ovarian cancer]. PMID- 7796653 TI - [Effect of epimedium sagittatum on soluble IL-2 receptor and IL-6 levels in patients undergoing hemodialysis]. AB - By using ELISA and assay of MTT participating in IL-6 dependent cell clone. The authors measured the circulating levels of soluble IL-2 receptor (sIL-2R) and IL 6 in patients undergoing hemodialysis (HD). Alterations of the above-mentioned parameters before and after a three-month course of treatment with Chinese drug Epimedium sagittatum on the same HD patients. It is confirmed that in patients with end-stage renal failure (ESRF), sIL-2R level elevated significantly, while IL-6 level decreased apparently (P < 0.01). Furthermore, levels of both sIL-2R and IL-6 could be restored to normal after treatment with Epimedium sagittatum. These findings indicated not only the presence of immunodeficiency in ESRF, but also the effectiveness of regulation with Chinese drug Epimedium sagittatum. PMID- 7796654 TI - [Detection of thyroid stimulating antibodies and TSH binding inhibitor immunoglobulins in patients with thyroid diseases and its clinical applications]. AB - Thyroid stimulating antibodies (TSAb) and TSH binding inhibitor immunoglobulins (TBII) were assessed in patients with thyroid diseases. The activity of TSAb and TBII was significantly higher in patients with untreated Graves' disease (GD) as compared with that in patients with remitted GD and Hashimoto's thyroiditis, while the latter two groups had higher TSAb and TBII activity than patients with thyroid adenoma or control subjects. Of 24 patients with untreated GD, TSAb and TBII were detected in 22 and 19 respectively. The positive rates of TSAb and TBII in patients with remitted GD or Hashimoto's thyroiditis were 0.48 and 0.44 or 0.231 and 0.615. Both TSAb and TBII were negative in patients with thyroid adenoma or controls. No statistical correlation was found between TSAb and TBII activity, suggesting the coexistence of heterogeneous populations of TSH receptor antibodies. PMID- 7796655 TI - [Effect of dietary and/or exercise intervention on incidence of diabetes in 530 subjects with impaired glucose tolerance from 1986-1992]. AB - 577 subjects with impaired glucose tolerance (IGT) aged from 25 to 74 were identified in Daqing in 1986. They were stratified according to BMI > or = 25 (352 cases) and BMI < 25 (225 cases) and subjects in each BMI group were randomly assigned to four groups: control, diet, exercise and diet plus exercise intervention groups (each group had similar age, BMI, fasting and 2-hour plasma glucose level). A six-year follow up study indicated that incidence of diabetes per 100-person-year was 15.7, 10.0, 8.3 and 9.6 in control, diet, exercise and diet plus exercise groups respectively. Proportional hazards regression analysis controlling for differences in baseline factors (age, sex, BMI and plasma glucose) showed that diet and/or exercise intervention were inversely related to the incidence of diabetes. The better the actual intervention, the less the incidence of diabetes. Therefore, the results strongly indicate that diet and/or exercise intervention treatment are effective methods to reduce the incidence of diabetes. PMID- 7796656 TI - [Early diagnosis of tuberculosis after kidney transplantation by determining serum anti-PPD-IgG]. AB - Tuberculosis is a common complication after kidney transplantation and is not easy to diagnose in the early stage. Determination of serum anti-PPD-IgG level in our laboratory indicated that it was positive in patients with active tuberculosis. The mean time (20.5 days) required to diagnose with this method was obviously shorter than that (66.8 days) required with bacteriology, pathology or imaging. There was no obvious rise in the serum level of anti-PPD-IgG in fever caused by other infections and rejection and the serum anti-PPD-IgG level in patients with tuberculosis controlled returned to normal. It is shown that determination of serum specific antibody is a better index for early diagnosis of tuberculosis complicating kidney transplantation. PMID- 7796658 TI - [Pharmacokinetics of oximes in organophosphorus poison]. PMID- 7796657 TI - [Progress in the study on the pathogenesis and therapy of anemia in rheumatoid arthritis]. PMID- 7796660 TI - [Strategy of drug treatment of gout]. PMID- 7796659 TI - [Research on osteoarthritis]. PMID- 7796661 TI - [Rheumatic diseases in China]. AB - To determine the prevalence of rheumatic diseases in Chinese of Han nationality in the north and the south of China, samples of 4,192 adults in Beijing (north) and 5,057 in Shantou (south) area were studied. The same questionnaire was administered to each subject surveyed. Physical examinations were done in all who gave positive answers. For those who gave positive response to certain set of questions, blood antinuclear antibody and rheumatoid factor tests and radiographs of hand and/or sacroiliac joint were done. The prevalence of definite rheumatoid arthritis (RA) was 0.34% in the north (95% confidence interval 0.20-0.51) and 0.32% (0.95% CI 0.16-0.47) in the south and ankylosing spondilitis was noted in 0.26% of both samples (95% confidence interval in the north 0.11-0.42 and in the south 0.14-0.40). Only 3 cases of systemic lupus erythematosus 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 examinations 5 times more commonly in the north than in the south (men 25.0% vs 5.3%, women 38.0% vs 6.5%) and knee problems 10 times (men 24.0% vs 1.8%, women 36.0% vs 3.4%) more commonly in the north; the difference was greatest in the age of 55-64. A further study in the south is planned to assess the contribution of inter-observer error and/or difference in cultural response to the north/south difference observed in the prevalence of general rheumatic symptoms and back pain. A search for environmental risk factors such as climate, diet, degeneration or overuse would then be indicated to explain these differences. PMID- 7796662 TI - [An epidemiological study of knee osteoarthritis]. AB - 2,063 adult people of a Beijing suburban village were surveyed for osteoarthritis of the knees. Questionnaire was completed in all. 799 (38.7%) responded to have knee joint pain. 311 with knee joint pain and 212 without knee joint pain were selected randomly for X-ray films of the knees. In the former group, 79 showed osteoarthritic X-ray changes and were thus diagnosed as such, accounting 24.7% of those with knee pain. In the latter group, all were not diagnosed as clinical osteoarthritis, yet 54 (25.5%) showed also X-ray osteoarthritic changes. In both groups the X-ray osteoarthritic changes increased in parallel with increase of age, reaching 78% in those aged 60 and more in the former group and 67% in the latter group. 100 retired cadres were similarly surveyed but all had X-ray films of the knees taken. 51 of 100 responded knee pain, out of whom 49 (95.9%) showed X-ray osteoarthritic changes and were thus diagnosed as such. The overall prevalence rate of osteoarthritis of knee in rural population as judged by the 523 who had taken X-ray films (people with and without knee pain are not entirely proportional) is about 9.6% and that of 100 aged retired cadres is 49%. Those with X-ray knee osteoarthritic changes but without knee pain were not categorized as clinical osteoarthritic cases. PMID- 7796663 TI - [Osteoarthritis: clinical and epidemiological investigation]. AB - A population study of 1,722 adults in Chenghai city, Guangdong province showed that the prevalence of osteoarthritis (OA) was 8.3% and there was no significant difference between male and female. The prevalence of OA increased after the age of 40 and reached a peak at 50-55 years. The prevalence of osteoporosis (OP) in OA patients of this population survey and in patients in our clinic was around 30%. OA accompanying OP was more frequently seen in female than male, especially in postmenopausal women. The results of CT screen of lumbar spine in 66 OA patients showed: 89.4% (59 cases) was associated with the protrusion of intervertebrale disc, occurring frequently at L4 and L5. MR imaging of 20 knee joints in 10 cases of OA patients with knee involvement showed: all of the patients were associated with one or all of the following conditions: chondropathies, degeneration or injury of semilunar plate, bursitis and synovitis. It is suggested that OA is a heterogeneous disorder and must be treated with different ways. PMID- 7796664 TI - [The role of intestinal permeability in the pathogenesis of ankylosing spondylitis]. AB - By use of low molecular weight polyethlene glycol (PEG400) as tracer, a revised Chedwick method with capillary gas chromatography was used to examine the intestinal permeability in 49 subjects including patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and healthy controls. Recovery percentage, maximal recovery percentage [Rmax(%)] and Rmax(w) were used to find the effect of bowel permeability in the pathogenesis and disease flare up of AS, as well as the role of HLA-B27 for the bowel permeability. The results showed that in AS group, the recovery of first component (242D) was higher and the Rmax(%) was lower than those in the controls. No statistical difference was found with other indexes. The results indicated that bowel permeability is not elevated in AS. The passage of enteral bacteria antigen into the host may not result from the process of nonspecific penetration. We postulate that there may somehow be a process of "active transportation" in the pathogenesis of AS. More studies of the process are necessary to clarify its importance in the early stage of AS. PMID- 7796665 TI - [Dynamic observation and significance of autoantibody against ADP/ATP carrier in dilated cardiomyopathy]. AB - The presence and dynamic change of autoantibody against ADP/ATP carrier in patients with dilated cardiomyopathy (DCM) was studied by using indirect micro solid-phase radioimmunoassay. A significant antibody titre was present in 16 of 48 DCM patients and most of them were in early stage of the disease. The titre of anti-ADP/ATP carrier antibody in DCM patients decreased gradually in a follow-up period of three months. The titre of this antibody in the serum from patients with coronary and rheumatic heart disease were within normal limits. Anti-ADP/ATP carrier antibody may play an important role in the pathogenesis, diagnosis and treatment of DCM. PMID- 7796666 TI - [The effect of prostaglandin E1 on myocardial ischemia reperfusion injury]. AB - The effect of prostaglandin E1 (PGE1) on ischemia reperfusion injury (IRI) was investigated. The changes of leucocytes in venous blood and infarcted myocardial tissue and the level of lipid peroxide (LPO), superroxide dismutase (SOD) and catalase (CAT) were also studied in these animal models at the same time. The experimental results were as follows: the count and activity of leucocytes and the level of LPO in IRI were obviously increased. The activity of SOD and CAT in the untreated group was much lower than that in the treated group (P < 0.01). The infarcted size (IS) was larger in the untreated group. The count of leucocytes was positively related with the level of LPO and IS, but negatively related with the activity of SOD and CAT. However, the relationship disappeared after the administration of PGE1. These data suggested that leucocyte plays an important role in IRI. PGE1 can inhibit leucocyte activity, decrease peroxidation, reduce LPO production and increase the activity of SOD and CAT. It can decrease the infarct size. PGE1 takes the main role in protecting IRI. PMID- 7796667 TI - Hepatitis B virus infection, the immune response and hepatocellular carcinoma. AB - More than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV) and have a 200-fold increased risk of developing hepatocellular carcinoma (HCC). This is one of the most common cancers in the world with a geographical distribution highest in areas where HBV is endemic. A number of molecular mechanisms have been proposed to explain this correlation including an acutely transforming viral oncogene; chromosomal aberrations due to HBV integration (i.e. deletions, translocations, duplications); activation of cellular proto-oncogenes; inactivation of cellular anti-oncogenes; and transactivation of cellular genes by HBV gene products. HCC usually develops only after 20-30 years of persistent HBV infection accompanied by hepatocyte necrosis, inflammation and regenerative hyperplasia. Because HBV is not directly cytopathic, liver injury must be immune mediated. Factors that predispose HBV infected individuals to develop HCC are chronicity, an immune response and liver injury rather than a direct genetic event. Hepatic injury and continuous hepatocyte regeneration may allow an accumulation of multiple mutational events sufficient for the emergence of HCC. Pathways which lead to chronicity, the immune response during HBV infection, mechanisms of pathogenesis and methods to prevent HBV infection are all relevant to the development of HCC. Recent studies characterizing the humoral and cellular immune responses in patients chronically infected with HBV and transgenic mouse models of HBV-specific immune tolerance and pathogenesis are providing new insights into the complex association between HBV infection and HCC. PMID- 7796668 TI - The role of superantigens in the immunobiology of retroviruses. AB - Murine mammary tumour viruses (MMTVs) are retroviruses that encode superantigens capable of stimulating T cells via superantigen-reactive T cell receptor V beta chains. MMTVs are transmitted to the suckling offspring via the milk. We have established that class II and B cell-deficient mice that were foster nursed by virus-secreting mice do not transfer infectious MMTVs to their offspring. No MMTV proviruses could be detected in the spleen and mammary tissue of these mice and there was no deletion of MMTV superantigen-reactive T cells. These results confirm that superantigen expression in the context of MHC class II molecules is required for MMTV transmission. We conclude that B cells are essential for the completion of the viral life cycle in vivo. This indicates that B cells are infected first and that viral amplification takes place only if infected B cells present the MMTV superantigen on their surface which, in turn, results in activation of T cells expressing the appropriate T cell receptor V beta chains. These activated T cells stimulate B cells which enables viral replication. Human T cells carry all the structural features required for an efficient response to murine retrovirally encoded superantigens. Superantigen-like stimulation of human T cells has been demonstrated in both infectious and autoimmune diseases. Human immunodeficiency virus may encode a superantigen but this has not been proven. PMID- 7796670 TI - Induction and regulation of CD4+ T cell subsets. AB - It is now generally accepted that CD4+ T cells can be divided into at least two distinct subsets: Th1 and Th2. Th1 cells characteristically secrete interleukin 1 (IL-2) and gamma-interferon (IFN-gamma) whereas Th2 cells produce mainly IL-4, IL 5 and IL-10. Studies from many laboratories have demonstrated that the balance between these two subsets of T cells frequently determines the outcome of infectious and autoimmune diseases. Several factors influence the preferential induction and regulation of Th1 or Th2 cells in vitro and in vivo. Mice were infected with the protozoan parasite Leishmania to show that the gene encoding a major surface glycoprotein of the parasite, delivered orally in a plasmid carried by an auxotrophic Salmonella typhimurium vaccine strain (BRD509), preferentially induced Th1 cells and protective immunity against a challenge infection. The protective effect of the vaccine was augmented by administration of BRD509 carrying the genes encoding IL-2, IFN-gamma or tumour necrosis factor alpha. Cloned mouse Th1 cells specific for malarial antigens have been used to show that nitric oxide (NO) can inhibit the production of IFN-gamma by Th1 cells. Oral delivery of antigen and selective cytokines may preferentially induce CD4+ T cell subsets. Modulation of NO synthesis may further influence this induction and sustain such selective responses leading to effective therapy. PMID- 7796669 TI - Assembly and transport of class I MHC-peptide complexes. AB - Peptides that are presented to T-cells by class I major histocompatibility complex molecules are derived from cytosolic proteins. They are generated in the cytosol and translocated into the endoplasmic reticulum (ER) by the transporters associated with antigen processing (TAP molecules). Competition experiments suggest that TAP molecules can specifically translocate a wide range of peptides from 8-13 amino acids long; longer peptides are less likely to be transported. A photoactivatable peptide derivative has been used to demonstrate that competition for transport into the ER reflects competition for a specific peptide-binding site on the TAP molecule. Class I molecules bind the translocated peptides in the ER thereby allowing their transport to the cell surface. The assembly of the class I-peptide complex in the ER is tightly regulated. The evidence suggests that class I heavy chains first dimerize with beta 2-microglobulin in a process mediated by the chaperone calnexin. The class I-beta 2-microglobulin dimer then physically associates with TAP molecules and is released for transport when it binds a peptide. PMID- 7796671 TI - The host response to lesions induced by human papillomavirus. AB - Human papillomaviruses (HPVs) are strictly intraepithelial pathogens: in the natural productive infection they induce benign epithelial proliferations of mucocutaneous surfaces, some of which may progress to malignancy. Benign HPV induced lesions are chronic persistent growths; high levels of viral antigen are expressed in the apparent absence of a host immune response suggesting that these viruses have evolved efficient mechanisms of immune evasion. Cell-mediated responses are central in the pathogenesis of HPV and regression of both cutaneous and genital warts histologically resembles a delayed-type hypersensitivity response (DTH). The antigen(s) in the wart against which this response is initiated are not known but in an experimental murine model DTH responses to the E6 and E7 proteins of HPV-16 can be elicited when viral antigen is presented via the epithelial route. Priming with low levels of viral antigen in this model induces non-responsiveness and the loss of DTH. In HPV-associated cancers the E6/E7 genes are expressed and an antibody response to the proteins is found in at least 50% of cases indicating that these oncoproteins are potential targets for immunotherapy. PMID- 7796672 TI - Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy. AB - Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy. PMID- 7796673 TI - Bone marrow-derived cells present MHC class I-restricted tumour antigens in priming of antitumour immune responses. AB - Many tumours express tumour-specific antigens capable of being presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules. Current models of antigen presentation predict that the tumour cell itself should present its own MHC class I-restricted antigens to T cells. Earlier cross-priming experiments have demonstrated that at least some MHC class I-restricted antigens may also be presented by bystander cells. There is no detectable presentation of MHC class I-restricted tumour antigens by the tumour itself during priming of tumour-specific responses. The tumour antigens are presented exclusively by host bone marrow-derived cells. These results imply that an efficient mechanism exists in vivo for transfer of MHC I-restricted antigens to bone marrow-derived antigen presenting cells. They also suggest that HLA matching may not be critical in the clinical application of allogeneic tumour vaccines. PMID- 7796675 TI - Potential antigenic targets on Epstein-Barr virus-associated tumours and the host response. AB - There is considerable variation in the degree of expression of viral genes among different tumours associated with Epstein-Barr virus (EBV). Immune control of tumours in immunosuppressed patients (immunoblastic lymphomas) can be exercised through a range of epitopes from cytotoxic T lymphocytes (CTL) covering the full spectrum of latent EBV gene products. A subunit vaccine based on an EBV CTL epitope from one of the latent genes is about to undergo human trial. The options for immune control of Burkitt's lymphoma are more restricted. Antigen expression is limited to a single nuclear antigen, EBNA1, and Burkitt's lymphoma cells are unable to process EBV latent antigens, presumably because of a transcriptional defect in TAP1 and TAP2 genes. In contrast with earlier suggestions that EBNA1 is not a target for CTL, there is a class II-restricted epitope within EBNA1. EBV infected B cells are unable to process this epitope endogenously. The most promising strategy for developing a vaccine against these tumours is to use a single subunit vaccine that incorporates multiple CTL epitopes from several human pathogens. PMID- 7796676 TI - Human T cell lymphotropic virus: necessity for and feasibility of a vaccine. AB - Human T cell lymphotropic virus types I and II (HTLV-I/II) are endemic in certain areas of the world. They cause two life-threatening diseases, adult T cell leukaemia/lymphoma and tropical spastic paraparesis. A vaccine is needed because in developing countries there are no other feasible preventive interventions against these diseases and in Western countries intravenous drug users at high risk for HTLV-I and HTLV-II infections and the health workers in contact with such populations must be protected. We have developed a rat model in which we observed variations of susceptibility to viral infection between inbred strains, the most susceptible being the Fischer F344, and the possibility of viral latency in the nervous system. We have prepared a recombinant adenovirus vector that expresses the HTLV-I envelope glycoprotein env in HeLa cells. A target human population in French Guyana, in which the prevalence rate reaches 5.6% in one ethnic group (Bonis), has been identified for possible intervention. PMID- 7796674 TI - Evasion of host immune responses by tumours and viruses. AB - Viruses and tumours use various mechanisms to avoid immune surveillance. Oncogenic viruses have achieved a balance with the immune system through evolutionary time to ensure long-term persistence. Mutations that promote escape mechanisms favouring tumour growth to the detriment of host survival through reproductive age offer no selective advantage and will not generally be maintained in the viral genome that persists in nature. Conventional (non oncogenic) and tumour viruses interact with various immune mediators and T cells in different ways. Oncogenic viruses cannot operate solely in the context of a lytic cycle, though this may be characteristic of the initial phase of infection that is limited by the acute immune response. Some oncogenic viruses interact with normal cellular growth control and signalling mechanisms. Synthesis of key viral proteins may be tightly controlled in replicating cells that are subject to T cell surveillance, such as basal epithelia, while productive infection occurs in non-proliferating progeny that are lost under normal physiological conditions, such as desquamating epithelia. Tumorigenesis may be an aberrant consequence of the molecular mechanisms needed to maintain this pattern of viral growth regulation in the context of the cell cycle. Vaccines designed to limit the acute phase of infection with cell-free oncogenic viruses should be as effective as those for conventional viruses. PMID- 7796677 TI - Vaccination against cutaneous and mucosal papillomavirus in cattle. AB - Viruses are responsible for approximately 15% of human cancer worldwide. Human papillomavirus and hepatitis B virus are the recognized agents of cervical and liver cancer, respectively, which together constitute 80% of all virally induced cancers. If measures could be found to bring viral infection under control, a great proportion of human cancer would be greatly reduced. Experimental vaccines are being developed against papillomavirus. In principle two different types of vaccine can be envisaged: prophylactic vaccines that would elicit virus neutralizing antibodies and would prevent infection and therapeutic vaccines that would induce regression of established lesions before progression to malignancy took place. The research on vaccines against human papillomavirus is hampered by the difficulties encountered in growing the virus in tissue culture and by the unacceptable nature of experimentation in humans. Effective vaccines, both natural and genetically engineered, have been developed against bovine papillomavirus and cottontail rabbit papillomavirus. The success obtained with the animal models supports the optimistic prediction that in the relatively near future vaccines will be available against the most problematic or potentially dangerous forms of papillomatosis in humans. PMID- 7796678 TI - Prospects for T cell immunotherapy of tumours by vaccination with immunodominant and subdominant peptides. AB - Immunotherapy of tumours by adoptive transfer of cytotoxic T lymphocytes (CTL) is now feasible in experimental murine systems. These CTL recognize peptide sequences of defined length presented by major histocompatibility complex (MHC) class I molecules. Effective eradication of large tumour masses requires co administration of interleukin 2. Tumour escape strategies are numerous but in various instances can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic virally induced tumours and other tumours requires novel strategies to overcome T cell inertia. We propose a strategy in which CTL are raised against target molecules of choice including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The steps proposed include: (1) identification of target molecules of choice. (2) Identification in these target molecules of peptides fitting MHC allele-specific peptide motifs involved in peptide binding to MHC molecules. (3) Evaluation of actual binding of such peptides to specific MHC class I molecules. (4) In vitro CTL response induction by such peptides, presented by highly efficient antigen-presenting cells such as antigen processing-defective cells carrying empty MHC class I molecules loaded with a single peptide or dendritic cells. Both types of cells are capable of primary CTL response induction in vitro. (5) Evaluation of proper processing by the demonstration of tumour cell lysis by these CTL. (6) Adoptive transfer of tumour-specific CTL generated in vitro or vaccination with peptides. These various steps have now been taken for several viruses, virally induced tumours and other types of tumours and the first indications that this strategy is useful have been obtained. PMID- 7796679 TI - [Relationship between bone fluoride content, pathological change in bone of aborted fetuses and maternal fluoride level]. AB - Relationship between bone fluoride content, pathological change in bone of aborted fetuses and maternal fluoride level was studied in 46 pregnant women and their inducedly-aborted fetuses. Results showed fluoride content in fetal femur averaged 368.2 micrograms/g, and 41.4% of the bone with pathological change. Fluoride levels in maternal urine and amniotic fluid and fluoride content in fetal femur and pathological change in fetal femur appeared a positive correlation between them. Femur fluoride content and pathological change of bone in fetuses born to mothers with mottling teeth were significantly greater than to those without them. Pathological change in fetal femur presented dose-response relationship with their bone fluoride content. When the latter reached greater than 500 micrograms/g, pathological changes occurred in 90% of the bone. PMID- 7796681 TI - [Comparison and evaluation of the methods of diet survey]. PMID- 7796682 TI - [Interventional measures in occupational hazards in village-and town-run industries and occupational health services]. PMID- 7796680 TI - [Effects of dust particle inhalation on pulmonary surfactant system]. PMID- 7796683 TI - [An epidemiologic study on pulmonary fibrosis caused by hard alloy dust]. AB - A cross-sectional study, with 1,237 employees solely exposed to hard alloy dust and 502 controls in four hard metal works and two tool and grinder manufacturers in China, was conducted. Results showed prevalence of symptoms of respiratory system, and abnormalities in lung function and serum level of ceruloplasmin and urine cobalt content in exposed group were significantly higher than those in controls. Eight cases of pneumoconiosis were detected by chest X-ray films with a prevalence of 0.65% and an average length of employment in dust environment of 25.2 years. It suggested hard alloy dust could cause pulmonary fibrosis and pneumoconiosis in exposed workers. PMID- 7796684 TI - [Studies on diagnosis for occupationally chronic toxic hepatopathy]. AB - Data from 10-to-17-year periodical physical examinations for 10,858 employees exposed to hepatotoxic chemicals were sorted out and analyzed, and 1,514 cases of suspected chronic toxic hepatopathy were detected. Causes of under-recognition of those were: (1) liver function tests now available being not sensitive enough; (2) limitations of conventional methods for diagnosis of hepatopathy by excluding other disorders; and (3) lack of diagnostic criteria for it. In the light of existing problems, the following diagnostic procedures were applied in the studies: (1) analyzing data dynamically to understand when and to what extent the liver damaged during their work; (2) exploring several more sensitive liver function tests to be used in the diagnosis, and (3) incorporating industrial hygienic files into clinical data to get preliminary diagnosis for it, and then to differentiate from other disorders and to establish a definite conclusion. With these procedures, diagnosis of occupationally chronic toxic hepatopathy was established in 1,035 cases of 1,514 suspected ones. PMID- 7796685 TI - [Studies on inhibitive effects of organic selenium on cell damage caused by SiO2]. AB - Changes in potassium content of macrophage in guinea pigs and in membrane protein of erythrocytes in rats caused by quartz dust, and the effects of selenium protein and selenium-containing polysaccharide of cell membrane on them were determined with atomic absorption spectrometry and electronic spin label. Results showed quartz could significantly decrease potassium content of macrophage with a dose-effect relationship. Potassium content in the exposed group could return to normal level as the control group by adding Se-protein into quartz dust. Rotational correlation times of the membrane protein in erythrocytes could be decreased by quartz dust, and Se-protein and Se-containing polysaccharide could make them normal. It suggested quartz could cause cell permeability significantly increased, cleavage of peptide-chain of membrane protein, degradation and cross linkage of protein, and cell damage, but organic selenium could decrease cytotoxicity caused by quartz dust and protect cells from the damage. PMID- 7796687 TI - [An epidemiological study on reproductive effects in female workers exposed to acrylonitrile]. AB - Four hundred and seventy-seven female workers exposed to acrylonitrile and 527 controls were studied by retrospective cohort method. Results showed incidence rates of pernicious vomiting and anemia, preterm delivery, and birth defects in exposed women were obviously higher than those in controls, with statistical significance. Logistic regression analysis revealed exposure to acrylonitrile in pregnant workers caused increasing risk of preterm delivery and birth defects. In addition, illness, medicine taking and X-ray irradiation during pregnancy related to the increase of incidence of preterm delivery in exposed women. PMID- 7796686 TI - [Effects of lead on neurobehavior and neurochemistry in rats]. AB - Effects of exposure to lead on neurobehavioral function, content of monoamine neurotransmitter in hippocampus, and brain level of lipid peroxide were studied in 45 SD rats. Results showed learning and memory abilities of the rats were affected in exposure to lead of 1333.3 mg/kg (with their blood lead level of 6.23 mumol/L), their motor activities changed and emotional status became unsteady with 266.7 mg/kg of lead (with blood lead of 4.20 mumol/L) and 1333.3 mg/kg of lead, respectively, and levels of dopamine neurotransmitter and its metabolites declined and those of lipid peroxide increased with increasing exposure to lead. It is postulated changes in levels of neurotransmitter, such as monoamine and lipid peroxide, could explain the mechanism for damage in neurobehavioral function caused by lead exposure. PMID- 7796688 TI - [Comprehensive evaluation of protective measures in electric welding]. AB - Protective effects of safety masks, eyewear, work clothes, gloves, periodically physical examination system, and ventilation and barriers at workplace, were evaluated by one-way analysis for handtorch welding, carbon dioxide gas protective welding, and argon-arc welding operations, etc. in township and village enterprises and state-owned enterprises by interviewing managers in the departments of technology and work safety and field investigating. Based on the results of one-way analysis of protective measures, comprehensive evaluations of various enterprises were made with a fussy mathematical model. Both enterprises in township and village level and of state-owned were graded as A on a basis of the evaluation, which will be helpful to the better management of occupational health in the future. PMID- 7796690 TI - [Preparation and identification of monoclonal antibody against sterigmatocystin]. AB - Compound antigen, bovine serum albumin-sterigmatocystin (BSA-ST) or hemocyanin sterigmatocystin (H-ST) was prepared by converting ST to its hemiacetal group in ST and taking ST conjugated to BSA or H. Balb/c mice were immunized with BSA-ST, and then their spleen cells were isolated and fused with SP2/0 murine myeloma cells. A hybridoma cell strain that could stably secrete monoclonal antibody against ST (McAb-ST) was selected, and both of their ascites and serum were rich in McAb-ST induced by cells of this strain. McAb-ST was identified as Ig-Gi with a molecular weight of 168,000 kd (53,000 for heavy chain and 31,000 for light one), and with an affinity constant of H-ST reaction of 1.29 x 10(9) mol/L measured by indirect competitive enzyme-linked immunosorbent assay (IC-ELISA). Relative cross reaction of McAb-ST with ST analogues was less than 2%. The minimal 0.5 pg/25 microliters of ST can be detected with IC-ELISA using McAb-ST and ST simultaneously, with a linear range of 0.1-10 ng/ml. PMID- 7796689 TI - [Inhibition of glutamate uptake in rat brain synaptosome by pyrethroids]. AB - In vitro studies showed deltamethrin (1 x 10(-7)-1 x 10(-4) mol/L) could inhibit 3H-DL-glutamate uptake in rat cerebral cortex and hippocampus synaptosome by 7.2% 21.5% and 10.4%-25.1%, respectively, with a dose-response pattern. But only in high-dose permethrin (1 x 10(-4) mol/L) can significantly reduce 3H-DL-glutamate uptake in rat hippocampus synaptosome. In addition, deltamethrin also can reduce 3H-DL-glutamate uptake in cerebellum and striatum of rats by 16.5% and 31.8%, respectively. It is suggested that both deltamethrin and permethrin, especially the former, can disturb the function of brain tissue in high-affinity-glutamate uptake with their alpha-cyano-group. So pyrethroids could play an important role in cerebral stimulation in mammals. PMID- 7796691 TI - [Monitoring of lead content in foodstuff in China]. AB - Lead contents in six kinds of foodstuff in China were monitored in 1992. Six hundred and three specimens of food were collected from the markets in Beijing, Shanghai, Jiangsu, Sichuan and Guangdong. Results showed that 96.2% of cereals, 84.4% vegetables, 97.6% dairy products, 96.0% eggs and, 100% meat and fish met the national food hygienic standards for lead allowable content. Daily dietary intake of lead of residents in six areas of China was lower than the provisional standard for Daily Allowable Intake of lead set by World Health Organization. PMID- 7796692 TI - [Changes and trend prediction in cancer morbidity of urban residents in Beijing]. AB - Data from a long-term cancer morbidity registry and notification system were analyzed dynamically. A theoretical model of grey system was established based on time-series changes in cancer morbidities to predict its trend by the year of 2001 in Beijing. Results show cancer morbidities in Beijing will increase yearly from 1991 to 2001, and overall morbidity rate of malignant tumor will increase to 179.9/100,000 from 162.5/100,000. Proportions of malignant tumor in different sites will change greatly. Morbidities of lung cancer and breast cancer will increase rapidly, of liver and colon-rectal cancer shoes an increasing trend, too, of esophageal and cervical cancer will decline steadily, and of stomach cancer will begin to decline. All these facts laid a scientific basis for the study on cancer prevention and control. PMID- 7796693 TI - Image processing algorithms for the automated micronucleus assay in binucleated human lymphocytes. AB - The frequency of micronuclei in binucleated lymphocytes (cytochalasin B assay) may serve as a biological dosimeter after radiation exposure. The automation of the micronucleus assay in binucleated human lymphocytes has been considerably advanced in recent years. In our studies for this purpose the detection of binucleated cells (BNCs) and the scoring of micronuclei (MN) was divided into two parts. First, detection of BNCs was feasible with low microscopic magnification (x 100). The positions of classified BNCs were stored. Second, after an automatic change of microscope objective, the stored BNCs were automatically analyzed in sequence at high microscopic magnification (x 630) for occurrence of MN. For both phases of image analysis we used empirical methods based on mathematical morphology. The system is able to recognize nearly 65% of BNCs with false positive decisions of 6% and about 75% of the MN with false positive decisions of 7%. PMID- 7796695 TI - Mouse testis cell sorting according to DNA and mitochondrial changes during spermatogenesis. AB - Flow cytometry can measure variations in DNA content and chromatin structure as well as dramatic changes in the mitochondria of germ cells during maturation from spermatogonia to elongated spermatids. Using 10-N nonyl acridine orange (NAO), an inner mitochondrial membrane dye, it is easy to follow mitochondria rearrangements. Mouse testis cells stained with the DNA fluorescent probe propidium iodide (PI) and analyzed by flow cytometry can be discriminated on the basis of their ploidy levels into five main regions corresponding to elongated spermatids, round spermatids, diploid, S-phase, and tetraploid cells. The simultaneous use of PI and NAO demonstrated the presence of cells having low and high mitochondrial content in the haploid, diploid, and tetraploid compartments. Eleven sorting windows were selected from the bivariate analysis (PI/NAO) and the corresponding cells were identified by microscopic observation. Cells were also discriminated by two parameter analysis of DNA content vs. cell diameter. The definition of seven different regions allowed us to determine NAO or rhodamine 123 (Rh 123) uptakes in each compartment. We observed that the ratio (Rh 123/NAO) dramatically changed according to the progression of cell differentiation which occurs during spermatogenesis. PMID- 7796694 TI - Comparative sperm chromatin structure assay measurements on epiillumination and orthogonal axes flow cytometers. AB - The sperm chromatin structure assay (SCSA) measures the susceptibility of sperm nuclear DNA to acid-induced denaturation in situ, and was developed on two Ortho flow cytometers, an FC200 [Becton Dickinson Immunocytometry Systems (BDIS), Westwood, MA] and a Cytofluorograf 30 (BDIS), both having orthogonal axes of fluorochrome excitation, emission, and sample flow. Sperm cells are first treated with a pH 1.4 buffer to denature DNA in situ and then stained with the metachromatic dye acridine orange (AO). The metachromatic fluorescence measured reflects relative amounts of denatured (red fluorescence) and native (green fluorescence) DNA present per cell. The extent of DNA denaturation is quantified by the calculated parameter alpha t [alpha t = red/(red+green) fluorescence]. Alpha t variables important for correlations with fertility and toxicant-induced chromatin damage include mean (X alpha t), standard deviation (SD alpha t), and cells outside the main population (COMP alpha t). Mean green fluorescence intensity is an important measure for DNA content and/or degree of sperm chromatin condensation. This study showed that the SCSA can be successfully run on two epiillumination-type instruments, an Ortho ICP22A (BDIS, San Jose, CA) and Skatron Argus (Tranby, Norway), and two additional orthogonal axes instruments, a Becton Dickinson FACScan (BDIS) and a Coulter Elite (Coulter Corporation, Hialeah, FL). Epiillumination instruments produced a different fluorescence distribution than orthogonal instruments, but the resulting alpha t values showed strong conformity and interpretation of results was the same. SCSA values obtained on the Coulter Elite were most similar to the Cytofluorograf 30; the FACScan green fluorescence distribution was narrower and allowed resolution of cell doublets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796696 TI - Flow cytometric measurement of NK cell immunoconjugates by pulse width processing. AB - Pulse width analysis, in flow cytometry, has been widely used for optimal cell size resolution in cell kinetics analysis. Pulses, generated by scattered light or fluorescence of cells, are electronically analyzed for their height and width. The information generated from these two properties of the pulses is utilized to distinguish signals from single cells vs. signals from cell clumps or aggregates. Pulse width, unlike pulse height, is more sensitive to differences in cell diameter, and therefore can discriminate very small differences in it, which pulse height cannot. We have exploited this property of pulse widths to measure immunoconjugates between NK cells and their targets. Discrimination of the free target cells from the conjugated ones is possible by the pulse widths of only light scatter signals, both forward and/or orthogonal. This resolution was not obtained if pulse height of the same signals was visualized. Using this resolution it was possible to distinguish single cells from the aggregates between target and effector cells. We propose that this is a better method for distinguishing conjugates than the method in which prior vital staining of cells is used. PMID- 7796698 TI - Induction of cell cycle perturbations by the tear gas 2-chlorobenzylidene malonitrile in synchronously and asynchronously proliferating mammalian cells. AB - The effects of the tear gas 2-chlorobenzylidene malonitrile (CS) on mammalian cell proliferation were studied in detail using bromodeoxyuridine/Hoechst flow cytometry. In synchronized (G0/G1-phase) Chinese hamster embryo (CHE) cells, exposure to CS (60 microM) caused a permanent arrest in the G0/G1 phase in 50% of the cells and a delayed G0/G1 phase exit. In asynchronously growing CHE cells, the CS-induced cell kinetic perturbations varied with the cell cycle stage during treatment. While G1-phase cells showed a delayed progression through S and G2/M phases, S-phase cells were mainly inhibited in the G2/M compartment of the first cell cycle. In contrast, CS-treated, asynchronous, amniotic fluid-derived, fibroblast-like (AFFL) cells exhibited a prolonged transit through the G2/M phase of the first cell cycle regardless of the cell cycle stage during treatment. This indicates that the induced cytotoxicity of CS is a function of both the cell cycle phase and the particular type of cells. PMID- 7796697 TI - S-phase arrest of nutrient deprived lung cancer cells. AB - The human small cell lung cancer cell line NCI-H82 was used to study the effect of nutritional status on cell proliferative parameters. Incorporation of bromodeoxyuridine (BrdUrd) was used to characterize actively proliferating cells and to obtain information on cell cycle dynamics. During several days, in which the culture medium was not changed, a gradual decrease in overall cell growth, labeling index, and vitality was observed. Simultaneously, an increase in the number of S-phase cells that did not incorporate BrdUrd was noticed. From a more detailed kinetic study on d 6 of nutrient depletion, it appeared that, although the cells incorporated BrdUrd, they stopped cycling. When the same cells were regrown in fresh culture medium, a delay of 10 h in G1-phase entry and exit was measured. After this delay the cells resumed the cell cycle at normal phase transit rates. In addition, BrdUrd unlabeled S-phase cells were gradually lost from the culture. Bivariate flow cytometric DNA/proliferating cell nuclear antigen (PCNA) and DNA/Ki67-antigen analyses confirmed a delay in G1 phase entry and exit. In this paper we show that nutrient depletion can cause cell cycle arrest as indicated by the occurrence of BrdUrd unlabeled S-phase cells. This arrest could lead to overestimation of kinetic parameters such as S-phase transit time (Ts) and potential time (Tpot) as determined after in vivo labeling of tumors. PMID- 7796700 TI - Chromosome specific DNA hybridization in suspension for flow cytometric detection of chimerism in bone marrow transplantation and leukemia. AB - Flow cytometry was used to measure the fluorescence intensity of nuclei that were subjected to fluorescent in situ hybridization in suspension with chromosome specific DNA probes. Paraformaldehyde-fixed nuclei were protein digested with trypsin and hybridized simultaneously with a biotin- and DIG labeled chromosome specific centromere probe. A number of probes were tested in the suspension hybridizations. The method yielded fluorescent hybridization signals that allow discrimination between Y chromosome positive and negative nuclei when analyzed by flow cytometry. The method is especially suited for analysis of bone marrow cells derived from patients who have received a sex-mismatched allogeneic bone marrow transplantation. Male leukemia cells with a trisomy for chromosome 8 were mixed with normal female cells and simultaneously hybridized in suspension with a DIG labeled probe specific for chromosome 8 and the biotin labeled Y chromosome probe. Y chromosome positive or negative nuclei were sorted onto microscope slides and subsequently classified as being leukemic or not by fluorescence microscopy, on the basis of the presence of a trisomy for chromosome 8. A 120 fold enrichment could be achieved when 300 Y positive nuclei were sorted from a mixture originally containing 0.5% leukemia cells. Given the specificity of the flow cytometry and FISH procedure, the combination of the two methods can reach a lower detection level of 1 per 250,000. PMID- 7796699 TI - Phenotype transition of CD4+ T cells from CD45RA to CD45R0 is accompanied by cell activation and proliferation. AB - An investigation of proliferation and activation events in subsets of human CD4+ cells, defined by their expression of CD45RA and CD45R0, is reported. A single laser based assay for the study of multiple surface antigens and two-parameter cell cycle analysis was used for sorting of and subsequent analysis of proliferation in CD4+CD45RA+ CD45R0-, CD4+CD45RA-CD45R0+ subsets and phenotypically intermediate stages. After labelling with BrdUrd, cells were sorted with flow cytometry on the basis of light-scattering properties and staining with anti-CD45RA, anti-CD45R0, and anti-CD4 markers. Sorted cells were double stained with anti-BrdUrd-antibodies and PI, and the frequencies of proliferating cells were determined. After 48 h, the highest rate of proliferation was found among cells with a phenotype intermediate between CD4+ CD45RA+CD45R0- and CD4+CD45RA-CD45R0+. After 72 h of culture, the situation was changed insofar as the point of highest proliferation had shifted towards the CD4+CD45RA-CD45R0+ population. These findings were further corroborated by four colour staining with anti-CD4, anti-CD45RA, anti-CD45R0, and Hoechst 33342. This indicates that the phenotype transition is accompanied by cell proliferation. The correlated temporal expression of antigens related to activation (HLA-DR, CD25, CD69, CD71) and cell adhesion (CD11a, CD54, L-selectin) in each of the different subsets was also investigated. All the activation markers CD25, CD69, and CD71 show a more heterogeneous pattern of expression among the CD4+ CD45RA-CD45R0+ cells than the CD4+ CD45RA+CD45R0- cells, indicating a subpopulation of CD4+CD45RA-CD45R0+ cells responding more slowly to the mitogenic stimulation. PMID- 7796702 TI - Differential effects of two fluorescent probes on macrophage migration as assessed by manual and automated methods. AB - Fluorescent probes have been utilized to label leukocytes for both in vivo and in vitro studies of cell migration; however, the effects of such probes on migration have not been determined. The aim of this study was to examine the effects of two commonly used fluorescent probes on leukocyte chemotaxis. J774 macrophages were labeled with either calcein-acetoxymethyl ester (calcein-AM) or 2',7'-bis-(2 carboxyethyl)-5-(and 6)-carboxyfluorescein, acetomethyl ester (BCECF-AM), then assayed for their ability to migrate to zymosan-activated serum (ZAS). Cell migration was quantified by two methods: visual counting of cells and measuring cell fluorescence. Using the cell counts, comparison of unlabeled and fluorescently labeled macrophages demonstrated that BCECF-AM decreased the number of cells responding to ZAS, while calcein-AM had essentially no effect. Neither probe significantly affected the number of cells migrating to medium alone. The inhibitory effects of BCECF-AM on cell migration increased with probe concentration (0.1-1.0 microM) and cell fluorescence. Cell viability was unaffected by either probe. In contrast to the results obtained by visual counting, measuring fluorescence of migrated cells did not reveal a significant difference between the chemotactic response of macrophages labeled with BCECF-AM and those labeled with calcein-AM. These experiments indicated that fluorescent probes can affect the chemotactic response and that inhibitory activity of these probes may not be detected when chemotaxis is quantified solely by automated methods. PMID- 7796701 TI - Flow cytometric monitoring of allergen induced basophil activation. AB - Human basophils express many clustered differentiation antigens (CD), including CD45; however, none are specific for these cells. In a previous study, we described a two-color immunofluorescence procedure, employing antibodies to CD45 and IgE for the cytometric evaluation of basophils. In the present work, we show that when sensitized basophils are stimulated by allergenic preparations, they demonstrate an upregulation of CD45 as well as a decrease in anti-IgE binding. Since CD45 antigen modulation was observed with all aeroallergens tested and the decrease in IgE expression varied with allergenic preparations, the measurement of CD45 upregulation was used to evaluate basophil activation. Using this approach, reproducible results were observed when atopic patients were tested at different time intervals. In addition, we show that the upregulation of CD45 on allergen stimulated basophils is a very rapid phenomenon that is observed after a few minutes and that this rapid flow cytometric method can also be used for investigations on nonallergenic mediators of basophil stimulation such as calcium ionophores. PMID- 7796703 TI - Superantigens as etiopathogenetic factors in the development of insulin-dependent diabetes mellitus. PMID- 7796704 TI - Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. PMID- 7796705 TI - Genetic epidemiology of non-insulin-dependent diabetes. PMID- 7796706 TI - The regulation of pancreatic islet blood flow. PMID- 7796707 TI - Antiherpetic activities of N-alpha-acetyl-nona-D-arginine amide acetate. AB - N-alpha-acetyl-nona-D-arginine amide acetate (ALX40-4C) was developed as a competitive inhibitor of the binding of the HIV Tat protein to its RNA target TAR, which is an intracellular interaction dependent on a short, arginine-rich sequence in Tat. ALX40-4C is a simple mimic of that domain, which is stabilised against enzymatic degradation through inclusion of D-amino acids and terminal protection. The drug inhibits HIV-1 in vitro and is currently being assessed in vivo. In the work reported here, potential activities of the compound against other viruses were examined. As expected, there was little or no activity against most viruses examined, except against some herpesviruses: HSV-1, HSV-2 and CMV. Maximal inhibition of HSV-1 in a plaque reduction assay required pre-incubation with the drug. Maximal inhibition of HCMV, which replicates more slowly than HSV 1, requires exposure to the compound within the first few hours of infection. It appears that the drug inhibits an early step in HSV and HCMV infection. Such a mechanism is consistent with that of other cationic, herpesvirus inhibitors. PMID- 7796708 TI - Imipenem and immune response: in vitro and in vivo studies. AB - Imipenem is a new beta-lactam antibiotic endowed with very high antimicrobial activity; it is used in severe infections which often occur in those conditions characterized by impairment of the immune system. The aim of this study was to evaluate the effect of imipenem on some immune functions, both in vitro and in vivo. The authors studied the effect in vitro of three different drug concentrations (15, 30 and 60 mg/l) on polymorphonuclear leucocyte (PMN) phagocytosis and superoxide anion production, as well as on lymphomonocyte proliferative response and cytokine production. Preincubation of PMN with the highest dosages (30 and 60 mg/l) was found to increase phagocytosis evaluated via both cytofluorimeter and chemiluminescence, while no effect was detected on superoxide anion production or on lymphomonocyte tests. In the in vivo study, the authors administered imipenem/cilastatin (1500 mg/day) to 15 elderly and diabetic patients, in whom both PMN functions (phagocytosis and superoxide anion production) and lymphocyte tests (CD3, CD4, CD8, CD19, IL2 and sIL2R serum levels) were studied before and on the 3rd and 7th days of treatment. The drug assimilation did not modify the lymphocyte parameters, whereas it increased PMN superoxide anion production and phagocytosis which were depressed in basal conditions. In the former case, such increase was slight and insignificant, whereas in the latter it was significant. PMID- 7796709 TI - Pharmacokinetic optimization of the treatment of oral candidiasis with fluconazole: studies with a suspension. AB - An open crossover study was performed in 12 healthy subjects to investigate the pharmacokinetics in saliva and plasma of a 100 mg oral dose of fluconazole, administered as either a capsule or as a suspension, the latter being used to rinse the mouth and retained for 2 min before being swallowed. In terms of fluconazole plasma concentrations the capsule and the suspension were essentially bioequivalent. While the saliva concentrations of fluconazole after capsule administration reached their peak at 3.0 +/- 0.8 micrograms/ml 4 h after dosage, administration of the suspension resulted in a mean peak concentration of 551.1 +/- 425.6 micrograms/ml 5 min after ingestion. The saliva concentrations decreased gradually after ingestion of the suspension, but were higher for 4 h than the corresponding levels from the capsule. The area under the curve (AUC) from 0 to 96 h of fluconazole in saliva was 227.7 +/- 73.8 h micrograms/ml after the suspension, compared to 123.5 +/- 25.5 h micrograms/ml after the capsule, indicating that the total drug exposure to the oral mucosa by the salivary route was enhanced more than 80% with use of the suspension. Four h after administration of the suspension, saliva and plasma concentrations of fluconazole were in equilibrium, at a saliva: plasma ratio of around 1.2. Taken together, the present results suggest that the treatment of oral candidiasis with fluconazole may be optimized by use of an oral suspension, as this delivers pharmacologically active levels of the drug to the site of infection by both topical and systemic routes. PMID- 7796710 TI - Further evidence for a peripheral sympathicolytic action of the antihypertensive cicletanine in rats. AB - The site and mechanism of action of the antihypertensive agent cicletanine have been studied. In the pithed rat model, intravenous (i.v.) cicletanine was able to reduce the elevated blood pressure induced by continuous infusion of the alpha 1 adrenergic agonist, methoxamine, in a dose-related manner. In strip preparation of the aorta from deoxycorticosterone (DOCA)-salt-treated rats, cicletanine was found to prevent the contraction induced by 1 microM noradrenaline. When subeffective doses of phentolamine (0.25 mg/kg p.o.) plus cicletanine (3 mg/kg p.o.) were given together, a clear-cut antihypertensive effect was observed in DOCA-salt rats. Moreover, subchronic administration of cicletanine (30 mg/kg p.o.), during the one month period of DOCA-salt administration to produce high blood pressure readings, was able to prevent cardiac noradrenaline depletion. These data suggest that the antihypertensive effect of cicletanine, which is clinically well tolerated, may be due to a multifactorial mechanism of its action, through which it might alter a number of physiological mediators while exercising a slight potency on each of them. PMID- 7796711 TI - Effects of sumatriptan on isolated rabbit heart. AB - Sumatriptan provokes, in healthy subjects as well as in those who suffer from hemicrania, a slight increase in both systolic and diastolic arterial pressure. It has also been shown to increase the pressure of pulmonary circulation and to reduce the calibre of coronary arteries. The present investigation was undertaken to study the effects of sumatriptan (75 ng/l) on isolated rabbit hearts. Fifteen isolated rabbit hearts, perfused according to Langerdoff's procedure, were divided into two groups: Group I (5 hearts), perfused with Krebs-Henseleit solution, as a control, and Group II (10 hearts), perfused with Krebs-Henseleit mixed with sumatriptan succinate (75 ng/l). After 30 min of perfusion, the basal values of heart rate (HR) dp/dt, systolic ventricular pressure (SVP), diastolic ventricular pressure (DVP) and coronary flow (CF) were measured. The above values in either control or treated hearts were measured 5, 15, 30, 45, 60 min after recording the baseline values. HR, SVP, DVP, dp/dt and CF did not show significant differences in the two groups. The present data suggest that sumatriptan does not exert any action on isolated rabbit hearts. PMID- 7796712 TI - Everninomicin, a new oligosaccharide antibiotic: its antimicrobial activity, post antibiotic effect and synergistic bactericidal activity. AB - Antimicrobial activity of everninomicin (SCH) 27899) in comparison with two glycopeptides (vancomycin, teicoplanin) and six beta-lactam agents was evaluated against recent clinical isolates of Gram-positive bacteria. Everninomicin showed the highest activity against the species tested and MICs90% of everninomicin against Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Clostridium difficile were 0.1, 0.1, 0.2, 0.39, 0.1 microgram/ml, respectively. MICs90% of everninomicin against methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were 0.78 microgram/ml. Laboratory induced resistance to everninomicin in strains of S. aureus and E. faecalis occurred in a stepwise manner and at a very slow rate. Post-antibiotic effect against strains of S. aureus and E. faecalis were 1.8 and 2.6 h, respectively, and a little longer than that of vancomycin. Adherence to glass surface of an MRSA strain was strongly repressed by the addition of sub MIC of everninomicin in combination with fosfomycin. PMID- 7796713 TI - Pharmacological mechanisms in cocaine's cardiovascular effects. AB - The squirrel monkey is a reliable model for the cardiovascular effects of cocaine in that it mimics the human response to cocaine; low to moderate doses of cocaine produce a sustained pressor effect and tachycardia. Pretreatment experiments have indicated the importance of alpha-1 and beta-1 adrenoceptor mechanisms in mediating the pressor and tachycardiac effects of cocaine, respectively. Little support for a role of dopaminergic mechanisms in the hemodynamic effects of cocaine has been found. Toxicity to cocaine is often observed hours after its administration, pointing to a potential role of the cocaine metabolites. Studies on the direct effects of a variety of cocaine metabolites indicate that their cardiovascular effects do not necessarily mimic those produced by cocaine, and therefore these differing effects of the metabolites should be considered when evaluating the cardiovascular toxicity of cocaine. Further, as these metabolites are present in the body for long periods of time, these results suggest a role of the metabolites in producing toxicity long after cocaine administration. Finally, studies using both dopaminergic and calcium channel antagonists indicate that the pharmacological mechanisms involved in the cardiovascular effects of cocaine are not the same as those involved in its behavioral effects. PMID- 7796714 TI - Cardiovascular effects of cocaine in humans: laboratory studies. AB - Studies in which healthy, carefully screened, experienced cocaine users receive cocaine under controlled laboratory conditions, although often overlooked by the medical community, are an excellent source of data on the cardiovascular effects of cocaine. Cocaine is generally self-administered in repeated-dose 'binges', and studies simulating this pattern provide interesting cardiovascular information, such as the selective development of acute tolerance or the unique effects of some drug combinations. Studies with intranasal, intravenous, and smoked cocaine all show that under conditions in which subjects are allowed to take cocaine repeatedly, heart rate generally returns to near baseline levels between doses despite gradually increasing cocaine blood levels. Blood pressure either shows the same pattern, or gradual increases with repeated dosing. Analyses of cardiovascular activity as a function of cocaine plasma level indicate the rapid development of acute (i.e., within session) tolerance to cocaine. Cocaine self administration often occurs in the presence of behavioral stressors, or in combination with other drugs of abuse or cocaine abuse treatment medications. Performance of a behaviorally-demanding task increases heart rate and blood pressure. When cocaine is taken prior to task performance larger increases in heart rate are observed than with either drug or task alone. An unexpected cardiovascular interaction was observed in subjects who inhaled cocaine and drank ethanol-containing beverages. This combination resulted in heart rate increases that were significantly larger than observed with either drug alone. Combinations of i.v. cocaine and smoked marijuana also increased heart rate above levels seen with either drug alone. A single intravenous dose of cocaine and morphine in combination, however, produced cardiovascular effects similar to those produced by cocaine alone. The effects of these drug combinations on blood pressure were often equal to the effect of one drug alone. Since cocaine is frequently taken in combination with potential treatment drugs, these interactions can be assessed under controlled settings prior to large-scale treatment studies. For instance, maintenance on the antidepressant desipramine increased baseline heart rate and diastolic pressure. Cocaine administration engendered increases in heart rate and blood pressure above the desipramine-elevated baselines. Clearly, drug interactions can have unexpected cardiovascular effects, and laboratory studies provide a controlled setting for understanding and studying these interactions. PMID- 7796715 TI - Effect of cocaine on vagal tone: a common factors approach. AB - This paper discusses a distinct cardiovascular pattern that is common to a wide variety of abused substances. The pattern consists of tachycardia that appears mediated by withdrawal of vagal inhibition, as indicated by decreases in cardiac vagal tone. This decrease in vagal tone was particularly robust with i.v. cocaine given to experienced cocaine abusers in a residential research setting. Following 40 mg i.v. cocaine, heart rate increased by approximately 30 beats/min at the same time that vagal tone decreased by approximately 2 log units. The theoretical significance of these findings is based on evidence that the results reflect a common factor among many abused drugs, but not the few aversive drugs that have been studied in this paradigm. PMID- 7796717 TI - Pharmacological evaluation of dimethylheptyl analogs of delta 9-THC: reassessment of the putative three-point cannabinoid-receptor interaction. AB - The basic premise underlying the cannabinoid pharmacophore is that at least three functional groups are involved in the interaction between the ligand and the receptor and that these functional groups in delta 9-THC comprise (a) C11, (b) the phenolic hydroxyl, and (c) the side chain. In order to assess the relative importance of the C11 position and the side chain, a series of C11 substituted analogs were prepared which contained a dimethylheptyl side chain. Consistent with previous studies, incorporation of a dimethylheptyl side chain dramatically enhanced both pharmacological potency in mice and receptor affinity. Incorporation of a hydroxy at C11 along with this branched side chain resulted in an extremely potent cannabinoid with ED50S of 0.01, 0.04, 0.16 and 0.04 mumol/kg in depression of spontaneous activity, reduction in body temperature, antinociception, and immobility, respectively. This compound was also very potent as a discriminative stimulus in a drug discrimination procedure and exhibited an extended duration of action. Its high affinity for the cannabinoid receptor (Ki = 400 pM) was consistent with this pharmacological potency. Incorporation of an oxo rather than a hydroxy reduced potency somewhat, although this analog was much more potent than delta 9-THC in most behavioral assays. The most striking observation was that incorporation of a carboxylic acid to form 11-nor-delta 9 THC-DMH-9-carboxylic acid did not eliminate pharmacological activity. This analog was as potent as delta 9-THC. The improbability that all three of the functional groups are interacting in a similar fashion with the receptor provides further support that the C11 position is not an essential requirement for activity. On the other hand, it is possible that substituents in the C9 region are interacting somewhere within or near the same site, but differently. PMID- 7796716 TI - Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug. AB - Currently, augmentation of sympathetic nervous system function produced by cocaine is thought to be due primarily to stimulation of sympathetic centers in the brain (central effect) and to inhibition of catecholamine uptake into postganglionic sympathetic nerve terminals (peripheral effect). In this review of our work, we present the following evidence that cocaine-induced changes in cardiovascular function, particularly those that peak within 1 to 5 min after an i.v. bolus injection of the drug, are due to a peripheral effect of the drug: (1) In both dogs and cats, cocaine potentiates the tachycardiac effect of neurally released and injected norepinephrine (NE). The time course of action and dosage range of cocaine that produces potentiation follows that which increases blood pressure (BP), heart rate (HR), rate-pressure product and coronary vasoconstriction. (2) Cocaine given in i.v. doses that increase BP in decerebrate cats (0.25-1.0 mg/kg) has no significant effect on directly monitored spontaneous cardiac sympathetic nerve activity (SNA). In fact, higher doses of cocaine (2-4 mg/kg, i.v.) consistently inhibit preganglionic cardiac and splanchnic nerve activity. (3) Cocaine (0.1-1.0 mg) administered directly into the blood supply of the hindbrain via the vertebral artery produces no increase in BP, HR or SNA in cats; instead, decreases in BP and sympathetic activity occur. The same dose (1 mg), injected i.v., does not depress BP or SNA. In addition, cocaine injected into the forebrain via the carotid artery or into the cerebral ventricles (0.1 1.0 mg) has very little effect on BP. Our results indicate that there is no significant excitatory effect of cocaine on CNS sympathetic centers, and that the sympathomimetic effects of cocaine on the cardiovascular system are likely to be mediated at peripheral sites. PMID- 7796718 TI - Assessment of attentional bias and mood in users and non-users of anabolic androgenic steroids. AB - Forty-six male strength athletes took part in a study to measure the effects of anabolic-androgenic steroids on attentional bias to aggressive cues. They were 16 current users of anabolic steroids, 16 former users and 14 non-users. Testosterone, deca-durabolin and anadrol were the three most commonly taken steroids during the last cycle. Users generally took 2-3 drugs during each cycle; the average cycle lasted 8-11 weeks and they had completed 3-4 cycles. The subjects completed visual analogue scales of current feelings and were presented with a modified Stroop Colour Word Conflict Task containing sets of neutral, verbally aggressive and physically aggressive words. Current users tended to rate themselves more negatively. Users took longer than former users to name the colours of all word sets but there were no significant differences between word sets. Therefore, attentional bias did not differ between groups but current steroid use produced subtle mood changes and slowed performance compared to users not currently taking steroids. PMID- 7796719 TI - Neuropsychological performance of recently abstinent alcoholics and cocaine abusers. AB - To examine possible influences of premorbid and comorbid factors on the neuropsychological test performance of recently abstinent (3-5 weeks) drug abusers, we studied 24 alcoholics, 23 cocaine abusers, and 22 healthy controls of comparable age and education. Both alcoholics and cocaine abusers performed significantly more poorly than controls on most measures of learning and memory, problem solving and abstraction and perceptual-motor speed, but the groups did not differ on the measure of sustained attention. Correlational analyses revealed no significant relationships between measures of childhood and residual hyperactivity and neuropsychological performance; scores on the Beck Depression Inventory were related only to performance on the Wisconsin Card Sorting Test. The findings indicate that abuse of cocaine or alcohol is associated with deficits on neuropsychological tests which cannot be attributed to specific premorbid or comorbid factors such as depression or childhood or residual attention deficit disorder. PMID- 7796720 TI - Substance use among schoolchildren in the north of England. AB - A confidential and anonymous survey of 3623 adolescents was carried out in eight schools (six state comprehensive and two independent) in Newcastle upon Tyne. The survey enquired about cigarette use, alcohol consumption and illicit drug use together with key demographic variables. The results showed that 21% were currently smoking and 11% on a frequent basis. Regular smoking was more prevalent among girls. There was substantial use of alcohol, with 75% having used, and 20% drinking on a regular basis. This high level of alcohol consumption may be characteristic of northern Britain. The relatively low reported use of cannabis and relatively high reported use of naturally occurring hallucinogens may constitute a further regional variation. A minority of the sample (1.5%) were using illicit substances on a regular basis. Findings are discussed in terms of previous literature. PMID- 7796721 TI - Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care. AB - Twenty-seven HIV-infected methadone maintenance patients who demonstrated problems adhering to zidovudine (AZT) were randomly assigned to a group that received eight weeks of weekday supervised therapy and dispensing of AZT or a group that received usual care of the clinic. Adherence was assessed by self report, erythrocyte mean corpuscular volume (MCV), Medication Event Monitoring Systems (MEMS), and pill counts. Subjects in the intervention group demonstrated significantly higher MCV levels during the intervention period than usual care subjects, with similar but non-significant trends for the three other adherence measures. MEMS percent indicated significant group differences on weekdays, but not weekend days. There were no differences at a one-month follow-up. Results suggest supervised therapy and dispensing may be an effective strategy for improving AZT adherence, but only while provided. Further research is needed to establish the effects of larger and longer lasting interventions. PMID- 7796724 TI - [Amyloid struma]. AB - A 71-year-old woman with a seven-year history of seronegative polyarthritis had to be intubated and ventilated because of acute respiratory failure. The chest radiograph and computed tomography revealed bilateral pleural effusions and massive enlargement of the thyroid which compressed the trachea. Concentration of the thyroid-stimulating hormone was slightly reduced, while that of peripheral thyroid hormone was normal. Histological examination of a goitre specimen after strumectomy showed macrofollicular goitre with massive amyloid deposits. Amyloid was subsequently also demonstrated in the gastrointestinal tract. The patient died 5 months later from respiratory failure. A second patient, 47 years old at hospitalization, had been suffering from arthritic psoriasis since she was a child and had been undergoing haemodialysis for renal failure caused by amyloid. She had undergone angiography because the haemodialysis shunt had become occluded. She had been admitted because of an increase in goitre size during the last 6 months and a malignancy was suspected. Computed tomography showed the thyroid enlargement with retrosternal extension and a nodule in the thyroid isthmus. After injection of contrast medium for the angiography she developed, on the basis of probably already existing hyperthyroidism with an increased level of thyroid-stimulating immunoglobulin, clinically and biochemically manifest hyperthyroidism, which was treated with thiamazole (15 mg daily) and propranolol (40 mg twice daily). Cytological examination of a fine-needle biopsy of thyroid tissue revealed amyloid deposits. The patient died 4 years later, shortly after bilateral hip replacement for femoral neck fractures. At autopsy a large amyloid goitre and amyloid deposits in the kidneys, gastrointestinal tract and coronary arteries were found. PMID- 7796723 TI - [Sarcoidosis in monozygotic twins]. AB - Identical (monozygotic) female twins both simultaneously developed acute sarcoidosis with unusual manifestations. Additional to pulmonary involvement they both also had hypercalcaemia with compensated renal failure. When seen at the age of 33 years, these findings were more marked in one of them (case 2) than in the other, and she also had granulomatous conjunctivitis, while in the other one (case 1) the dominant sign was widespread lymph node enlargement. Both were also found by magnetic resonance imaging to have multiple lesions in the white matter, interpreted as the morphological correlate of neurosarcoidosis. But they caused clinical symptoms (visual disorder, unsteady gait) in only one sister (case 1). Treatment with prednisolone largely normalized the lung functions in case 2, completely in case 1, and renal functions in both. But when the daily prednisolone dose was reduced to below 10 mg, the pulmonary symptoms recurred. These observations indicate that even in chronic sarcoidosis acute episodes may occur, with involvement of multiple organs and other rare complications. The manifestations of the underlying disease in identical twins and the similarities of its course in the two sisters underline the possible role of genetic factors in the pathogenesis of sarcoidosis. PMID- 7796722 TI - [The clinical importance of scintigraphy with the murine monoclonal antigranulocyte antibody BW 250/183 for the diagnosis of prosthesis-related endocarditis]. AB - Thirty-eight patients (16 men, 22 women; median age 62.5, range 7 to 80 years) were enrolled in a prospective study to assess the clinical utility of radioimaging using the antigranulocyte antibody BW 250/183 in suspected valve endocarditis. Eighteen patients had prosthetic valve endocarditis according to clinical criteria (surgical confirmation in 8 patients), the remaining 20 patients served as controls. All patients underwent transthoracic and transesophageal echocardiography. Eight to 10 MBq of technetium-99m-labeled antibody were intravenously injected and single-photon emission computed tomography (SPECT) of the thorax was performed after 20 to 24 h. Echocardiography revealed pathological findings in 16 of 18 patients with endocarditis (sensitivity 89%) and was false positive in one of 20 control subjects (specificity 95%). Scintigraphy was true positive in 14 of 18 patients with endocarditis (sensitivity 78%) and false positive in three of 20 control subjects (specificity 85%). Scintigraphy was true positive in the patients with false negative echocardiography and vice versa (sensitivity for both methods combined 100%, specificity 80%). In all five follow-up patients, scintigraphy became negative parallel to clinical improvement. This suggests that scintigraphy indicates the floridity of the inflammatory process. In clinically suspected prosthetic valve endocarditis with equivocal echocardiographic findings, SPECT using the antigranulocyte antibody BW 250/183 may provide valuable additional diagnostic information. PMID- 7796725 TI - [The current status of funnel chest treatment]. PMID- 7796726 TI - [The hyperventilation syndrome]. PMID- 7796729 TI - [Is peptic ulcer an infectious disease?]. PMID- 7796728 TI - [The meaning of the carcinoembryonic antigen]. PMID- 7796727 TI - [The duty of fee reduction according to Article 6 a GOA. Gebuhrenordnung fur Arzte]. PMID- 7796730 TI - [Is peptic ulcer an infectious disease?]. PMID- 7796732 TI - [The recurrent risk for birth defects]. PMID- 7796733 TI - The implications of acquired immunodeficiency syndrome (AIDS) in otolaryngology. PMID- 7796731 TI - [Milk consumption and bone mineral content]. PMID- 7796734 TI - Temporal bone fracture with dislocation of the incus. PMID- 7796735 TI - Vocal fold masses associated with leukoplakia. PMID- 7796736 TI - Nasal osteotomies--two parts. PMID- 7796738 TI - CAT-astrophic allergies (a kitty letter). PMID- 7796737 TI - Endoscopic excision of an antral lesion via inferior meatal antrostomy. PMID- 7796739 TI - AIDS in the field of otolaryngology. PMID- 7796740 TI - AIDS: lessons from the last decade and prospects for the future. PMID- 7796741 TI - Universal precautions for the otolaryngologist: techniques and equipment for minimizing exposure risk. AB - HIV infection transmitted from a patient to a surgeon is a real concern but a remote possibility. However, given the professional and personal impact of HIV seroconversion on a physician, preventive measures need to be instituted. The CDC has developed a policy of universal precautions to help to minimize this risk. We review various measures to institute this policy and other measures that can reduce exposure to HIV. These protocols, when instituted, can maximize safety for all health care professionals and their patients. PMID- 7796742 TI - OSHA standards for blood-borne pathogens--strategies to increase compliance among otolaryngologists. PMID- 7796743 TI - Audiological changes associated with HIV infection. PMID- 7796744 TI - The management of sinusitis in patients infected with the human immunodeficiency virus (HIV). AB - As the Human Immunodeficiency Virus (HIV) has extended its influence across the United States, otolaryngologists have been increasingly called upon to manage its various head and neck manifestations. Sinusitis is a very prevalent, yet difficult, management problem in this patient population. The pathophysiology of sinusitis in this setting relates to altered helper T-lymphocyte function, an abnormal inflammatory response as well as increased IgE-mediated inflammation. Chronic HIV-related sinusitis is often due to Pseudomonas aeruginosa, Staphylococcus aureus, or anaerobic bacteria, and empiric antibiotic therapy must include these potential pathogens. Early cultures can facilitate organism specific antibiotic therapy. Aggressive treatment with decongestants, topical nasal steroids, mucoevacuants and occasionally antihistamines should be included at maximal tolerated doses. When medical therapy fails, surgical drainage can be a safe and effective management option. Appropriately directed medical, and occasionally surgical, therapy can lead to a dramatic clinical response and provide an improved quality of life in this patient population. PMID- 7796745 TI - The human immunodeficiency virus and facial plastic surgery. AB - The Human Immunodeficiency Virus (HIV) has imparted a number of concerns involving patient care and management as well as health care worker safety upon most surgical practices. Although these concerns are not often discussed in the context of facial plastic surgery (or particularly cosmetic surgery), they remain important issues. These issues are discussed with respect to public health policy, ethics and legality. The pathophysiological considerations for decision making and care for HIV disease in the facial plastic surgery practice are addressed. PMID- 7796746 TI - Complications following bilateral turbinectomy. AB - Thirty four patients undergoing bilateral inferior turbinectomy for obstruction of the upper airway are prospectively reviewed. The indication for the operation was persistent nasal obstruction interfering with sleep and speech. Their ages ranged from seven years to 50 years. The most common post operative complications were synaechiae (15%), atrophic rhinitis (15%), persistent obstruction (12%) and abnormal nasal sensation (9%). PMID- 7796747 TI - Prevalence and risk factors of parasitic infections among under-five Sudanese children: a community based study. AB - A community based prospective study was conducted among randomly selected 300 children aged less than five years selected from three camps of the police force in Khartoum from 534 households representing a total population of 4962 individuals. The study was planned to determine the prevalence and type of parasitic infestations and the related risk factors in that community. From the 300 children, 298 stools specimens were examined: 116 were positive for a single parasite, while samples from 15 children showed ova and cysts for two types of parasites giving a prevalence rate of 44%. The commonest infestations were Giardiasis (21.1%), Taeniasis (10.4%) and Enterobiasis (7.4%). Non pathogenic E. coli, E. histolytica and Taenia saginata were detected in 2.7%, 0.7% and 1.7% of stools specimen respectively. Children aged between 3 years and above were the most affected group and the infection rate was highest among the illiterate, overcrowded and large sized families. Malnourished children comprised 9.4% of the study group but there was no significant association between undernutrition and the overall prevalence of intestinal infestations, although Giardia lamblia significantly affected the undernourished group. PMID- 7796748 TI - Age and sex graded helminth infections in a Nigerian village. AB - Prevalence of helminth parasites was carried out in both male and female villagers graded into three age groups (5-14 years, 15-25 years, 26-55 years). Children between 5 and 14 years of age had the highest prevalence of Ascaris, Schistosoma haematobium and Trichuris while the villagers between 26-55 years of age had lowest prevalence of these parasites. However, hookworms were highly common among the villagers aged between 26 and 55 years and least common among the school children aged between 5 and 14 years. Female children between the ages of 5 and 14 years and males of the same age group were highly infested with Ascaris and Trichuris. This finding in a Nigerian village suggested that helminth infestation is age and sex dependent which is therefore a factor of the frequency in host-parasite contact determined by mode of life of the parasites and the hosts. PMID- 7796750 TI - Bacteraemia in patients presenting with fever. AB - In three studies, in Ghana and Kenya, blood from 639 patients admitted with fever was cultured. Standard treatments were antimalarials (54-100%) and antibiotics (39-90%). According to the criteria in use, however, only 10-31% had malaria alone; of those who received antibiotics, 66% were diagnosed with malaria, gastrointestinal infections, post-operative recuperations, circulatory problems, central nervous system disorders or FUO, and did not need antibiotics at the first encounter. For those with wounds and abscesses (8%), generalised antibiotic treatment can also be questioned. Bacteraemia was found in 71 (11.3%) patients; in the HIV patients, however, 5 (23%) of 22 had bacteraemia. This is a minimum incidence, since culture techniques were not optimal for the isolation of fastidious microorganisms. The most prevalent organisms isolated were Salmonella, Klebsiella/Enterobacter and S. aureus. Resistance (intrinsic and extrinsic) in the Gram- bacteria was high: 31-100% were resistant to amoxycillin, 0-80% to cotrimoxazole, 15-95% to chloramphenicol and 9-15% to gentamicin. The need for cultures and sensitivity tests for patients with prolonged or undiagnosed fever is stressed. Specific treatment should be given only when infections, whether malarial or bacterial, have been positively diagnosed. PMID- 7796749 TI - Sero-prevalence to hepatitis B and C virus infection in refugees from Mozambique in southern Africa. AB - Serological markers for evidence of past exposure to hepatitis B virus (HBV) and hepatitis C virus (HCV) were investigated in a cohort of refugees from Mozambique. Serological markers for past exposure to HBV were detected in 56% of the population and, in addition, 13.2% carried the HBV surface antigen. Anti-HCV antibodies could be confirmed in 3.2% of the population and occurred mostly in the older individuals. Only one anti-HCV antibody positive individual was positive for HBsAg. Immunity to rubellavirus had reached 85% by 11 years of age. PMID- 7796751 TI - Successful management of vesicovaginal fistulae at St. Gaspar Hospital, Itigi, Singida, Tanzania: a preliminary report. AB - Twenty five patients with vesicovaginal fistulae were managed at St. Gaspar Hospital, Itigi, Tanzania between February 1993 and March 1994. Most of them, 92% were repaired vaginally routinely using the Martius labial flap and 8% were repaired transabdominally because the fistulae were inaccessible vaginally as they were vesicouterine or vesicocervical fistulae. The success rate was 96% after the first operative attempt. PMID- 7796752 TI - The status and consequences of Mansonella perstans infection in Calabar, Nigeria. AB - Two aetiological studies on filariasis were conducted from January to June, 1993. In the first study, 690 blood samples clinically diagnosed of filariasis were examined. In the other, 150 blood samples and 150 skin snips collected from the same group of eye clinic Patients clinically diagnosed of filariasis were investigated. Of the 690 subjects, 108 (15.64%) had filariasis with M. perstans and Loa loa accounting for 98.15 and 1.85% of positive cases respectively. Among the eye clinic patients, 16% had M. perstans while O. volvulus was seen in 4% of patients. There was no concurrent infection with these two agents. A statistically significant association existed in the frequency of M. perstans in the different ages treated (p > 0.01) while non existed by sex (p > 0.01). The possible involvement of M. perstans in ocular filariasis and its treatment are discussed. PMID- 7796753 TI - Hospital catchment areas and surgery in Meru district, Kenya. AB - This study of the geographical locations of homesteads of patients undergoing surgery at three hospitals in Meru district, Kenya, showed largely overlapping catchment areas. It also showed catchment areas varying in size with the type of surgical operation under study: Caesarean section, exploratory laparotomy, uterine evacuation, tubal ligation, and normal child delivery. We conclude that catchment areas vary with the disease condition and the health care intervention under study. A precise definition of the catchment area population concept should be developed by ministries of health and then explained to district health teams and health care facility managers for local use in epidemiological surveillance and health care planning. PMID- 7796754 TI - Anorectal malformation presenting as Hirschsprung's disease: a case report. AB - A 3.8 kg female baby, who was born on 7-2-92 by normal vaginal delivery at a zonal hospital in the Southern Highlands of Tanzania, was initially noted to have had an "ectopic" anus (an ano-perineal fistula) but was otherwise normal. She had delay in the passage of meconium upto the third day, and by the fifth day had developed marked abdominal distension. Following a period of unsuccessful saline "enemas" she had to undergo a right transverse colostomy in the fourth week (which relieved the distension) for what was then presumed to be Hirschsprung's Disease. She was referred to the National Referral hospital in Dar es Salaam a year later, where she was found to have an entirely intra-pelvic sacrococcygeal teratoma in association with a "low" anorectal malformation. This unusual case is of interest because of the rare association of intrapelvic sacrococcygeal teratoma with anorectal malformation which led to the initial mis-diagnosis of hirschsprung's disease. PMID- 7796755 TI - Early cessation of breast feeding as a major cause of severe malnutrition in under twos: a hospital based study--Dodoma Region, Tanzania. AB - One hundred and ten consecutive children under two years of age were admitted because they were affected by severe Protein Energy Malnutrition. They were investigated to know the precipitating cause of their condition. 68 (62%) of them had a history of early weaning from the breast before 2 years, which was followed by a drastic drop of the growth curve. 16 (15%) of them adopted unilateral breast feeding. The study confirms the danger of stopping breast feeding before two years. This contrasts with other findings from Uganda, Zambia and Botswana which indicate that prolonged breast feeding is associated with higher prevalence of malnutrition in children. Further studies from other countries are necessary and opportune since the basic socio-economic conditions of the population, especially when these are as low as the case in Dodoma Region. PMID- 7796756 TI - Orofacial lesions as indicators of HIV/AIDS among dental patients in Kenya. AB - Despite an estimated prevalence of 3-5% of HIV infection in Kenya, little has been reported on the occurrence of oral lesions amongst the afflicted individuals. We report ten cases who presented with orofacial lesions and subsequent serological evaluation confirmed them seropositive. In the light of the numerous problems facing clinical staff in less developed countries, these findings underscore the significance of clinical identification of more probable HIV patients on the basis of orofacial signs. Continuing education with respect to HIV infection through wider dissemination of information on orofacial signs to clinical staff especially in the context of invasive care and containment of infection are recommended. PMID- 7796758 TI - Cost effectiveness in routine radiological investigations. PMID- 7796757 TI - The Spectrum Anaemia Banding Index (SABI): a new tool to assess collective anaemia levels. PMID- 7796759 TI - Radiological behaviour of the thymus in chest infection in the underfives. AB - The thymus in the paediatric chest will often give radiological appearances of very intriguing nature. It is known to react dramatically to stress factors such as infection or trauma. Gross hypertrophy following atrophy has been documented in many cases. In this paper the author scrutinizes one hundred anteroposterior chest radiographs of children under the age of five years suspected of having chest infection. Thymocardiac ratio is determined. It is concluded that in children under five years, the thymus generally decreases in size with age and that often the thymus will undergo atrophy as a primary response to infection. PMID- 7796760 TI - Ecology of Sergentomyia garnhami, (Diptera:Psychodidae) in a kala-azar endemic area of Tseikuru, Kitui District, Kenya. I: The breeding sites. AB - The breeding sites of S. garnhami and other phlebotomine sandflies were investigated from February 1989-June 1990. Sandflies were recovered from 15 out of the 17 ecological habitats studied while S. garnhami was recovered from fourteen. Termite hills were the most preferred breeding sites for most phlebotomine sandflies but it was not possible to identify the preferred breeding sites of S. garnhami as all the sites yielded only one to three flies. S. garnhami were recovered from soil samples from both inside and outside human homes as well as from sylvatic sites. Daily pattern of emergence of sandflies showed that 60 days were sufficient for most sandflies to emerge while at least 100 days were required for S. garnhami. PMID- 7796761 TI - Ecology of Sergentomyia garnhami, (Diptera:Psychodidae) in a kala-azar endemic area of Tseikuru, Kitui District, Kenya. II: Day resting sites. AB - A search for the day resting sites of S. garnhami and other phlebotomine sandflies in ten ecological habitats in Tseikuru area of Kitui District, Kenya, was carried out between November and December 1990. S. garnhami was collected in nine out of ten sites investigated, suggesting a wide distribution of the resting sites. S. garnhami constituted 23.4% of the total collections with termite hills being the most preferred site. Weekly trapping records showed that S. garnhami appeared in the field three weeks after the first rains of the season. PMID- 7796763 TI - Breastfeeding: past, present and future. PMID- 7796762 TI - Pattern of Schistosoma mansoni infection after intervention in Mwea irrigation scheme in Kenya. AB - A longitudinal study of Schistosoma mansoni reinfection rate was carried out in an endemic area of Kenya, after intervention. Intervention measures applied involved chemotherapy, community mobilization to effect change in water contact habits and faecal disposal. This paper focuses on S. mansoni reinfection pattern over a two-year period. The age group 5-19 years showed an increasing trend of reinfection as compared to the 30-59 years age group. More than 50% in the 5-19 year age group had been reinfected by twelve months of follow-up. They were also responsible of 91% of all the egg-load and 83% of all the infections at the end of the study period. Since majority of the 5-19 year age group comprises school children, there is an urgent need of including issues related to schistosomiasis in the school curriculum especially in the endemic areas. PMID- 7796764 TI - A study of breastfeeding and the return of menses in Hoima District, Uganda. AB - The effect of breastfeeding on reestablishment of ovulation and fertility and on birth spacing are now well known. A study was conducted on lactational amenorrhoea (LAM) at 180 days in Hoima District, Uganda in order to understand whether and how LAM could be applied in fertility control and birth spacing. Since the introduction of supplementary food by Ugandan women does not replace or substitute for breastfeeding, a study was designed to determine if LAM was effective irrespective of supplementation of infant's diet. One hundred and fifty four mother/child pairs were entered into the study and 134 women completed the sixth month of the study. At the end of the period, eighty four women (62.7%) were amenorrhoeic of whom only 33 (39.3%) were exclusively breastfeeding and no woman had dropped out of the study because of pregnancy or the use of other family planning methods other than LAM. The study confirmed that LAM could be applicable in Uganda to the majority of the breastfeeding women (62.7%). It is expected that if health workers increase the intensity of breastfeeding support as well as the women's knowledge and motivation to use LAM for family planning, this would contribute to children's health as well as to birth spacing that is one of the major factors related to infant deaths. According to data from this study, the return of menses is irrespective of whether supplements have been introduced and their frequency. PMID- 7796765 TI - Breastfeeding and immunity to intestinal infections. AB - The purpose of this study was to compare immune response in breast and non breastfed children presenting with diarrhoea at Paediatric Observation Ward, Kenyatta National Hospital (KNH-POW) and Maternal and Child Health Clinic, Pumwani Maternity Hospital (PMH-MCH). Blood and stool samples were collected from the first four consecutive children aged 5 years and below per day, presenting with or without diarrhoea from January to December, 1992. The stools were tested for total IgA by single radial immunodiffusion (SRID) and specific IgA by enzyme linked immunosorbent assay (ELISA). Peripheral blood CD4 and CD8 enumeration was done by flow cytometry. Stools were cultured for bacteria on selective media while ova and cysts of parasites were identified by wet preparation microscopy. A total of 457 children were enrolled into the study, 69.6% of whom presented with diarrhoea. Breastfed children tended to have a shorter duration of diarrhoea than either mixed fed or bottle fed (8.3 vs 9.8 vs 11.2 days, p = 0.2). In general, E. coli were more commonly isolated from breastfed than mixed fed or bottle fed (56.7% vs 43.9% vs 28.9%, p = 0.004) while intestinal parasites were mostly in bottle fed than mixed or breastfed children (28.8% vs 8.2 vs 0.8, p < 0.004). However, when children with diarrhoea were considered, E. coli was more frequently isolated from bottle fed children who presented with diarrhoea than without (26.7% vs 7.7%, p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796766 TI - Measles in infants: a review of studies on incidence, vaccine efficacy and mortality in east Africa. AB - Control of measles in developing countries is complicated by high incidence and mortality among infants. Hospital-based and community-based studies from East Africa were reviewed with respect to the reported incidence and mortality of measles and vaccine efficacy/seroconversion rates after the administration of measles vaccine to infants. The studies reviewed confirm that measles is particularly severe in infants, and some indicate that vaccination before 9 months with standard vaccine could be effective and have beneficial effects for children aged 6-9 months, while other studies refute this finding. Due to the high incidence and mortality of measles in infants, alternative control strategies are essential to reduce measles mortality. Further studies are needed on the effects of a two-dose schedule vaccinating at 6 and 9 months, which in mathematical modelling shows considerable benefit. Improved management of measles cases, including the administration of vitamin A could be considered as a complementary strategy for reducing measles mortality, especially in infants. PMID- 7796767 TI - Typhim Vi vaccine against typhoid fever: a clinical trial in Kenya. AB - Safety, tolerance and immunogenicity of the purified Vi polysaccharide vaccine (Typhim Vi) against typhoid fever was evaluated in primary school children aged 5 15 years. A total of 435 children were vaccinated, each with a single intramuscular injection in the left deltoid muscle. One hundred and ten children were randomly selected for blood samples on day 0 (pre vaccination) and day 30 (post vaccination). Vi antibodies studied by Radio immuno assay (RIA) on 97(88%) paired sera showed a seroconversion rate of 76.2% and seroprotection rate after vaccination was 74.2%, while 6.2% of children already had protective immunity before vaccination. The vaccine was well tolerated. Most commonly reported reactions were mild pain at site of injection (83%), and a few complained of mild swelling (4.6%), induration (1.1%), itching (1.1%) and headaches (1.4%). All reactions were of mild severity and disappeared within 24 to 48 hours. PMID- 7796768 TI - Paediatric morbidity and mortality at the Eldoret District Hospital, Kenya. AB - Over an 18 month period, there were 4,720 paediatric admissions at the Eldoret District Hospital in Western Kenya. The most frequent 20 diseases were identified and their respective case fatality rates calculated. Malaria was the most common cause for admission (33.0%) but the fourth most common cause of death with a case fatality rate of 2.2%. The overall mortality rate on the paediatric wards was 8.2% with 64.9% of the deaths occurring within the first 24 hours of hospitalization. Three-fourth of all admissions were due to four diseases: malaria, pneumonia, gastroenteritis and measles. Targeted interventional programmes aimed at these 4 diseases, coupled with a comprehensive primary health care system, would most likely result in much less morbidity and mortality for the children in the district. The systems for routinely collecting and storing medical records were found to be substandard, making it very difficult to accurately monitor morbidity and mortality. PMID- 7796769 TI - Choice of resting sites by Anopheles gambiae (Diptera: Culici) in Mwea Rice Irrigation Scheme, Kirinyaga District, Kenya. AB - Investigations on Anopheles gambiae were carried out in Mwea Rice Irrigation Scheme, Kenya, to determine their preference for resting on various colours of fabrics and bare walls inside rural houses. The inside wall surface of each house was divided into upper, middle and lower sections and the section further partitioned into subsections measuring 0.6 x 0.3m. Two sets of experiments were conducted: one in which the walls were partly fitted with one colour of fabric at a time (double-choice situation), while in the other the walls were fitted with a combination of six colours (red, black, yellow, white, green and blue) of fabric at once, (multiple-choice situation). The number of mosquitoes resting on each of the pieces of cloth pinned to the walls and the uncovered subsections of the wall were recorded for each section of the wall after 24 hours. The results showed resting preference for cloth covered parts of the walls. The white colour was found to best attract mosquitoes followed by colours red, yellow, black, blue and green. The hanging strips in the middle of the houses had fewer mosquitoes resting on them than those on the wall. PMID- 7796771 TI - Comparison of urine filtration and a chemical reagent strip in the diagnosis of urinary schistosomiasis in Ethiopia. AB - The diagnostic efficacy of a chemical reagent strip (Ames Multistix) was compared with syringe-Nytrel urine filtration technique in the detection of S. haematobium infection at varying disease endemicity levels in the Awash Valley of Ethiopia. In low endemicity area (Afambo), the reagent strip showed highest sensitivity, specificity, positive predictive value and negative predictive value of 80%, 96%, 40% and 99% respectively at "1+ limit" of microhaematuria. In the moderate (Dahitele) to high (Enta Doyta) areas, the highest diagnostic values of 77%, 83%, 56% and 93% respectively and 78%, 67%, 51% and 87% respectively were obtained at "trace limit". Using these cut-off points of haematuria, the prevalence of S. haematobium were 4.5%, 30.8% and 47% at low, moderate and high endemicity areas compared to 3.2%, 21% and 31% respectively using the filtration technique. A highly significant (maximum Kendall's tau = 0.44271; p < 0.002) was observed between N + 1 transformed geometric mean egg counts and micro-haematuria in the 10-19 years of age at all levels of endemicity. The efficacy and simplicity of chemical reagent strips and limitations of single parasitological examinations are discussed. PMID- 7796770 TI - Loa loa antigen detection by ELISA: a new approach to diagnosis. AB - Circulating immune complexes associated Loa loa antigen in sera of 27 subjects with Loa loa (13 'occult' and 14 microfilaraemic infections) was detected with Polyethylene glycol enzyme linked immunosorbent assay (PEG-ELISA) in a controlled study. Loa loa antigen was detected in all 27 sera. There was no correlation between antigen levels and microfilaraemia density. Cross reaction with Mansonella perstans was found. Although this serological test is able to detect all Loa loa infections, its use is limited by cross reaction with other filariasis. It is hoped that sensitivity will be improved by using monoclonal antibodies. PMID- 7796772 TI - Evaluation of the use of plain cervical spine radiography in patients with head injury. AB - The records of 457 head trauma patients who underwent plain cervical spine radiography following head injury between January 1991 and December 1991 inclusive were reviewed. Seventy-six patients (17%) all above ten years of age had abnormalities; forty five were clinically suspected to have cervical spine injury because of cervical tenderness and/or neurological deficits and in the remaining thirty-one patients the cervical spine injuries were detected first on plain radiograph. The 31 vertebral injuries consisted off fracture-dislocations 12 fractures, 4 dislocations and one odontoid fracture. None of the 235 patients below the age of 10 years had cervical vertebral or cord injury. It is recommended that plain cervical spine radiography be performed on all patients with head injury associated with altered level of consciousness and who are above ten years of age. PMID- 7796773 TI - An outbreak of influenza A/H3N2 in a Zambian school dormitory. AB - There was an outbreak of "a mysterious disease" at a Zambian school dormitory in September, 1993. Investigation with questionnaire and collection of throat swab specimens for virus isolation were carried out on 46 patients to identify the causative agent. In this outbreak, most of the patients showed similar symptoms such as fever, headache, sore throat, cough, etc. The disease had spread to all dormitories within a couple of days after the onset of the first cases. From these patients, 13 influenza viruses A/H3N2 were isolated on MDCK cell line. This was a first ever confirmed outbreak of influenza virus infection in Zambia. PMID- 7796776 TI - The prevalence of hepatitis B surface antigen (HBsAg) among drug-dependent patients in Jeddah, Saudi Arabia. AB - This study was undertaken to determine the prevalence of HBsAg among drug dependent patients in Jeddah, Saudi Arabia. Over a period of 10 months, 1498 patients admitted for drug dependence were tested for HBsAg. For each patient, the age and route of drug abuse were recorded. All the HBsAg positive patients were further tested for HBeAg and anti-Hbe. 244 patients were positive in HBsAg, giving a prevalence of 16.3%. Considered separately, the prevalence of HBsAg among drug users and non-intravenous drug users were 18.5% and 6.7% respectively. 225 (92.2%) of the 244 HBsAg positive patients were intravenous drug users. Of the 244 HBsAg positive patients, 35 (14.4%) were positive for HBeAg. The persistence for years of HBeAg in chronic HBsAg carriers may cause chronic liver disease and primary liver carcinoma. There is a need for more public education on this condition in order to control its spread and to prevent future complications. PMID- 7796775 TI - The neutralizing capacity and sodium content of antacid brands on the Kenyan market. AB - Seventeen brands of antacid products available on the Kenya market were investigated for their acid neutralising capacity and sodium content. Thirteen tablet products gave neutralising capacity per tablet of between 4.7 to 14.12 mMol hydrochloric acid. The neutralising capacities for the suspensions ranged between 11.97 to 34.32 mMol hydrochloric acid for 10ml suspension. The lowest neutralising capacities were obtained for products based on compound magnesium trisilicate and higher capacities for those containing magaldrate, or magnesium hydroxide or magnesium carbonate in combination with other ingredients. The fastest rate of neutralization was obtained with preparations containing carbonates and the lowest by compound magnesium trisilicate. The sodium content for the preparations was between < 0.001 mEq to 0.732 mEq sodium per minimum recommended dose. The study shows a high degree of variation in both the acid neutralising capacities and the sodium content of the different brands investigated. PMID- 7796774 TI - Evaluation and surgical treatment of solitary thyroid nodules. AB - This is a prospective study based on 146 consecutive thyroidectomies over a two year period (July 1990 to June 1992). All patients with solitary thyroid nodules which were suspicious or equivocal on fine needle aspiration cytology (FNAC) were subjected to a hemithyroidectomy plus isthmal resection. 60% of all the thyroidectomies were for solitary thyroid nodules of which 15% were malignant. This mode of surgery is suggested for these patients as it is an acceptable although controversial method of treatment for early localized differentiated thyroid cancer. This is justified by the high incidence of malignancy and the difficulty encountered in most of our hospitals regarding adequate assessment of such patients to decide whether surgery is indicated or not. There is also the problem of all those "enucleated" nodules especially in remote areas which are not subjected to histopathological diagnosis. What about the patient who never returns for follow-up? PMID- 7796778 TI - Phytobezoars: a revisit to an unusual cause of acute small bowel obstruction. AB - Phytobezoars or undigested food concretions in the gastrointestinal tract are mostly due to ingestion of astringent immature fruits following gastric surgery and can lead to the serious complication of acute small bowel obstruction. We are reporting a case of acute small bowel obstruction in a 40 year old Turkish male, 48 months following bilateral vagotomy and pyloroplasty. Important clinical pathological features are emphasised to increase the awareness of this rather uncommon cause of acute intestinal obstruction. PMID- 7796779 TI - Validation of methods for estimating habitual diet: proposed guidelines. PMID- 7796777 TI - Retrospective study of alleged sexual assault at the Aga Khan Hospital, Nairobi. AB - A retrospective audit of all the rape cases reported at the Aga Khan Hospital, Nairobi over a two year period was carried out. Out of 37 victims, 86.6% were less than 30 years old and 73.4% did not know who the assailant was. 80% of the victims reported to the hospital within 24 hours of the incident taking place and in 4 (10.8%) of the victims-vaginal swabs grew N. gonorrhoea. None of the victims opted for prosecution and none were referred for further counselling. We recommended that alleged rape victims be seen by a qualified gynaecologist or police surgeon and that they should be examined, investigated and managed by a standard protocol. PMID- 7796780 TI - Urban/rural differences in red blood cell fatty acid composition, plasma lipids and diet in Melanesian Fijians. AB - OBJECTIVE: The aim of the study was to compare red blood cell (RBC) fatty acid composition, plasma lipids and lipoproteins and dietary intake between urban and rural Melanesian Fijians. DESIGN: A cross-sectional study was performed in a random subsample (n = 154) from a total survey population of 589 subjects. SETTING: Melanesian Fijians living in the relatively urban settlement of Nabua, Suva and On the remote island of Qamea (rural) were studied. RESULTS: The proportions of myristic acid (1.4% versus 0.3%, P < 0.001) and arachidonic acid (10.1% versus 11.4%, P < 0.01) were significantly higher and proportions of oleic acid (14.4% versus 13.2%, P < 0.05) and linoleic acid (11.9% versus 8.1%, P < 0.001) were significantly lower in RBC from rural compared with urban men, and a similar pattern was seen in women. Plasma cholesterol levels were significantly (P < 0.05) higher in the rural subjects. Urban/rural differences in plasma cholesterol levels were not significant when the proportion of RBC myristate was taken into account. CONCLUSIONS: The results suggest that consumption of myristic acid from coconut fat is greater and the intake of linoleic acid is less in Fijians living on a remote island and may contribute to their higher plasma cholesterol levels compared with their urban counterparts. PMID- 7796781 TI - Effect of neutralized and native vinegar on blood glucose and acetate responses to a mixed meal in healthy subjects. AB - OBJECTIVE: To investigate the influence of sodium acetate and acetic acid from vinegar on blood glucose and acetate response to a mixed meal in healthy subjects. DESIGN: Five healthy subjects consumed in random order six test meals consisting of 100 g of sliced lettuce dressed with olive oil (Blank), olive oil plus 1 g acetic acid in the form of vinegar (AcOH), or olive oil plus sodium acetate in the form of vinegar neutralized to pH 6.0 with sodium bicarbonate (AcNa). On three occasions test meals were followed by a challenge consisting of 50 g carbohydrate portions of white bread (Bread). Glucose and acetate concentrations were measured in arterialized capillary blood before and until 95 min after the meals. Ultrasonography was performed in four other subjects to measure gastric emptying times after AcOH + Bread and AcNa + Bread. RESULTS: Blood acetate response over 95 min was markedly reduced after AcOH and AcOH+Bread meals compared to AcNa and AcNa + Bread. Similarly, the glucose response was depressed by 31.4% (P = 0.0228) after AcOH+Bread with respect to AcNa + Bread and Blank + Bread. No difference was observed between gastric emptying times after AcOH + Bread and AcNa + Bread. CONCLUSIONS: The results suggest that oral acetic acid and acetate might have a different effect on acetataemia and that a limited dose of vinegar, in the form of salad dressing, is sufficient to influence significantly the glycaemic response to a mixed meal in normal subjects by a mechanism related to acidity but not to gastric emptying. PMID- 7796783 TI - Multi-frequency bioelectrical impedance for assessing total body water and extracellular water in elderly subjects. AB - OBJECTIVE: The objective of this study was to investigate the utility of multifrequency bioelectrical impedance for the estimation of total body water (TBW) and extracellular water (ECW) in an elderly population. DESIGN: Body impedance at 8 frequencies (1-1350 kHz) was measured in duplicate within 1 week. TBW and ECW were determined using deuterium oxide and potassium bromide dilution respectively. SETTING: At the Department of Human Nutrition. SUBJECTS: 81 women and 36 men, aged 63-87 years, volunteered as subjects. RESULTS: Application of prediction equations from the literature, which are mostly based on impedance measurements in young and middle-aged subjects, resulted in large prediction errors of TBW and ECW which were related to the water distribution of the body. New sex-specific prediction equations for the estimation of TBW and ECW were developed for the elderly population and internally validated in random sub groups. TBW and ECW were best predicted using impedance at frequencies of 5 and 50 kHz respectively, and by using body weight. Prediction errors for TBW were 3.1 kg (7.3%) and 2.7 kg (8.5%) and for ECW 2.2 kg (12.3%) and 1.0 kg (7.4%) for men and women respectively. CONCLUSIONS: Multi-frequency impedance measurements are useful to assess TBW and ECW in groups of elderly subjects. However, the prediction errors are larger compared to young and middle-aged subjects, and are related to body water distribution. Individual errors are sometimes unacceptably large. PMID- 7796782 TI - The influence of body build on estimates of body composition from anthropometric measurements in premenopausal women. AB - OBJECTIVE: To assess the influence of body build on the bias and limits of agreement for estimates of body fat obtained from anthropometric prediction equations when compared with the same data obtained by dual energy X-ray absorptiometry (DEXA). SURVEY DESIGN AND SUBJECTS: Ninety-one premenopausal women, aged between 20 and 54 years, were chosen to represent a range of skeletal body build (relative sitting height 0.50-0.56) and body fatness [body mass index (BMI) 18-34 kg/m2]. Measurements of weight, sitting height, stature, skinfold thickness, waist, umbilical and hip circumference and total body resistance and reactance were made on all subjects by standard techniques after an overnight fast. A DEXA measurement of total body fat, fat-free soft tissue and total body bone mineral mass was also obtained within 2 weeks of the anthropometric assessment. RESULTS: At the group level the mean difference (bias) between DEXA and the anthropometric estimates of body fat was similar for all three anthropometric estimates ranging from 2.7 kg with impedance to 1.8 kg with skinfold thickness. The 95% limits of agreement were also similar, ranging from +/- 5.3 kg with body mass index to +/- 4.1 kg with impedance. Umbilical circumference, BMI and the amount of bone mineral expressed as a proportion of the fat-free soft-tissue mass were all significantly (P < 0.01) correlated with the level of bias between DEXA and the anthropometric estimates of body fat. This was not the case for relative sitting height or measures of body fat distribution. Regression equations which included BMI or umbilical circumference in combination with the predicted estimates of body fat essentially eliminated the association between the level of bias in predicted body fat and the level of body fatness. They also reduced the 95% limits of agreement between DEXA and the anthropometric estimates of body fat. CONCLUSIONS: Using DEXA estimates of body fat as the standard of reference our results suggest that the comparability and precision of body fat estimates derived from age- and/or sex-specific anthropometric prediction equations based on skinfolds and BMI, but not impedance, can be improved by adjusting for differences in BMI and umbilical circumference respectively. PMID- 7796786 TI - Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. AB - DESIGN: Placebo for 3 months, followed by 30 mg/day zinc gluconate in identical capsules. SETTING: Diabetic out patients clinic at the University Hospital, Grenoble. SUBJECTS: Diabetic patients cared for type I diabetes mellitus. 22 patients began the study, 4 dropped out. 10 patients suffered of an early retinopathy, 8 patients had no retinopathy. INTERVENTIONS: In this order: T0 biological measurements, 3 months placebo treatment, T1 biological measurements, 3 months zinc gluconate treatment, T2 biological measurements. Plasma Zn, Cu, Se, thiobarbituric acid reactants and antioxidant enzymes were measured [plasma and red glutathione peroxidase (Se-GPx), red cell superoxide dismutase (Cu-Zn-SOD)]. RESULTS: Lower plasma zinc level in the two groups. An increase in zinc level was observed and was more important in diabetic patients with no retinopathy (P = 0.05). The thiobarbituric acid reactants were above the reference values in all the patients, and were decreased at T2 (P < 0.05). Increase of GPx activity after zinc supplementation in patients with retinopathy. CONCLUSIONS: Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation. Moreover this supplementation decreases lipid peroxidation. The effects of zinc are different in diabetic patients with or without retinopathy. The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself. PMID- 7796785 TI - Effects of low-fat milk and fermented low-fat milk on cholesterol absorption and excretion in ileostomy subjects. AB - OBJECTIVE: To study small bowel cholesterol absorption and sterol excretion in order to explain possible serum cholesterol-lowering mechanisms of low-fat milk products. DESIGN: Two 24-h sterol balance studies with 1 litre of low-fat milk or one litre of fermented milk, in random order, added to a controlled diet. [3H]Cholesterol absorption was measured during each period. The results were compared to those on two 24-h periods with isocaloric amounts of lemonade given to the same basic diet, before and after the study. One litre of the two milk products was also consumed in addition to their normal diets in a cross-over design of 3 weeks and with run-in and run-out periods of 2 weeks each with 1000 ml of lemonade preceding the balance studies: SETTING: Outpatient clinic, where the subjects were eating their meals during the day and ileostomy bags collected. SUBJECTS: Nine ileostomy subjects, who have earlier participated in similar studies, volunteered for the study. All subjects completed the study. RESULTS: Cholesterol absorption was highest (66%) in the lemonade period, intermediate in the low-fat milk period (61%) and lowest in the fermented low-fat period (55%) (P < 0.05 for differences). Net cholesterol excretion (excretion minus intake) and calculated endogenous cholesterol excretion were significantly (P < 0.05 for differences) higher in the low-fat milk period than in the lemonade period and the fermented low-fat milk period. No significant change in serum cholesterol was, however, seen after 3 weeks on each milk regimen. CONCLUSION: Assimilation of cholesterol by microorganisms could possibly explain the reduced uptake of cholesterol with fermented milk. The mechanism behind the increased endogenous cholesterol excretion, induced by low-fat milk, is unclear. PMID- 7796784 TI - Smoking and its effects on maternal body composition in late pregnancy. AB - OBJECTIVE: To assess the possible impact of smoking on body composition at the 34 39 weeks of pregnancy, and its consequences on birth weight. SUBJECTS: 31 smokers and 31 non-smokers matched by age, gestational age and percentage of standard weight (PSW). Smoking mothers had 5 cigarettes or more per day during the whole period of pregnancy and non-smoking mothers never smoked. METHODS: A cross sectional study was conducted in an urban Public Health Center. Anthropometry and the deuterium dilution technique were used to determine body composition. The statistical analysis used a t-test for matched pairs to assess significance of the means difference for each variable. RESULTS: Suprailiac and subscapular skinfolds were found to be larger in non-smokers; this difference was significant for the suprailiac skinfold (P < 0.05). No significant difference was found in total body fat, total body water and fat-free mass obtained with the deuterium dilution technique, or FFM determined by anthropometry. Infants' birth weight was similar in the two groups of mothers. CONCLUSION: These findings suggest that pregnancy does not modify the pattern of body fat distribution already present in smokers before conception. Infants' birth weight was similar in both groups, probably due to no difference in fat-free mass and body fat. The physiological effect of nicotine (e.g. on prolactin, micronutrients), seems to be clearer during lactation and infant growth. PMID- 7796787 TI - Relationship between mothers' and newborns' nutritional and blood lipid variables. AB - OBJECTIVE: To study the relation between anthropometry, diet and blood lipids during pregnancy and anthropometry and cord blood lipids in newborns. DESIGN: Longitudinal study during pregnancy. SETTING: Population study. SUBJECTS: A group of 70 volunteer pregnant women attending the Maternity Advisory Service were recruited at the 1st trimester and studied during pregnancy. By the end of the study 17 women had dropped out of anthropometry and diet assessments and 21 had left blood lipid analysis. Anthropometric measurements and cord blood lipid determinations were carried out respectively on 43 and 28 newborns. INTERVENTIONS: Diet history; current methods for anthropometry and blood lipid determinations. RESULTS: The highest values for energy and other nutrient intakes were observed at the 2nd trimester. According to the recommendations usually made, protein and fat intakes were high, and carbohydrate intake too low. This was observed especially at the 3rd trimester. Significant relationships between protein, fat and carbohydrate intake (as a percentage of energy) during pregnancy and anthropometric variables in newborns and cord blood lipids (particularly for boys) were found in the group of mothers and their respective newborns. Few correlations between mothers' and newborns' levels of blood lipids were observed for girls. CONCLUSIONS: The results do not show considerable diet changes during pregnancy. The impact of mothers' diet on fat deposition in newborns and cord blood lipids seems to be sex-linked and more important for boys. PMID- 7796788 TI - Assessment of sodium and potassium in processed foods in an urban area in China. AB - OBJECTIVE: To identify commonly consumed processed foods with high sodium (Na) content and sodium to potassium (Na:K) ratio for the purpose of using this information in a community-based nutrition education programme. DESIGN: Calculations of Na and K intake were based on the data of a dietary survey carried out in Tianjin in 1992. All processed foods were randomly sampled based on manufacturers and market survey. SETTING: The survey was conducted in the urban area in Tianjin, China. PARTICIPANTS: 2317 subjects aged 15-64 years old were included in the dietary survey. The response rate was 95%. MAIN RESULTS: The mean sodium intake was 6517 mg in men and 5708 mg in women. 38% of the total Na intake came from processed foods and condiments in both of the urban men and women in Tianjin. 122 processed foods with sales volumes were identified. Most of the processed foods had high Na content and high Na:K ratio, especially Na-rich condiments, salted vegetables, fried dough cake and sausages. The Na content of most processed foods in Tianjin was higher than the mean value reported in the Chinese Food Composition Table. CONCLUSION: Processed foods contribute an important part of dietary Na in the urban diet in Tianjin. It is necessary to initiate nutrition intervention activities aiming at regulations on the Na content of processed foods and to advise the people to reduce consumption of salty foods. PMID- 7796789 TI - Differences between immature and adult rats in brain glutamate decarboxylase inhibition by 3-mercaptopropionic acid. AB - Glutamate decarboxylase (EC 4.1.1.15, GAD) activity was studied in the brain of 12-day-old and adult rats treated with 3-mercaptopropionic acid (3-MPA), an inhibitor of GAD competitive with glutamate. Control GAD activity in the brains of immature animals (91.8 +/- 18.2 nmol/h/mg of protein) was lower than that of the adult rats (228 +/- 37.5 nmol/h/mg of protein). Brain GAD inhibition in adult rats was 58% at the onset of seizures (9 min on the average after administration of 70 mg 3-MPA/kg). At the same time, 3-MPA-treated young rats exhibited 76% inhibition of GAD despite the fact that at 9 min these animals were not yet having seizures. At the onset of seizures (19 min after 3-MPA on the average) their GAD activity remained at the same level. The difference between the groups was not related to the presence of the coenzyme pyridoxal-5'-phosphate in the enzyme assay. The inhibition of GAD by 3-MPA in vitro in the immature and adult brains was similar (Ki at 5.1 microM and 4.8 microM concentrations of 3-MPA, respectively). Identical values were found for Km of GAD (at 4.5 mM concentration of L-glutamate). Calculations based on the results suggest that 3-MPA enters the immature brain more easily than the brain of the adult animals. While GAD inhibition by 3-MPA is the primary cause of seizures, their onset is influenced by other factors, in which the immature brain differs from the adult one and which may include less sensitivity to GABA decrease due to relative overactivity of the GABA system. PMID- 7796791 TI - Gabapentin potentiates the conductance increase induced by nipecotic acid in CA1 pyramidal neurons in vitro. AB - The anticonvulsant gabapentin (1-(aminomethyl)cyclohexane acetic acid) has been found to be effective for treatment of partial seizures, but the mechanism of action is unknown. Recent evidence from the rat optic nerve suggests that gabapentin may enhance promoted release of GABA, which is thought to be due to reverse operation of the GABA transporter. We have used whole-cell patch clamp recordings from CA1 pyramidal neurons in hippocampal slices to directly measure currents induced by nipecotic acid (NPA) during exposure to gabapentin. Under control conditions, pressure microejection of NPA increased whole-cell conductance with a reversal potential equal to the chloride equilibrium potential. This response was mimicked by GABA application, and blocked by bicuculline. The response to NPA was also present after blockade of synaptic transmission in the presence of calcium-free solution. These results are consistent with NPA promoting nonvesicular release of GABA from neighboring neurons or glia via reverse operation of the GABA uptake system, which then activated GABAA receptors on the recorded neurons. In control solution, the response to NPA slowly decreased over 45 min to approximately 50% of the initial response, consistent with GABAA receptor 'rundown'. However, in the presence of gabapentin there was a slow increase in the response, reaching approximately 170% of the control level after 45 min of gabapentin exposure. These results demonstrate that gabapentin enhances the promoted release of GABA by more than three-fold. The potentiation of the NPA response may be due to gabapentin increasing cytosolic GABA in neighboring cells via a delayed metabolic effect, and would have the functional effect of increasing neuronal inhibition during periods of hyperexcitability. PMID- 7796790 TI - Role of choroid plexus epithelium in the removal of valproic acid from the central nervous system. AB - Previous experiments suggest the primary route of valproic acid (VPA) removal from the rabbit central nervous system (CNS) is by probenecid-sensitive transporters at the blood-brain barrier but not at the choroid plexus. The purpose of this study was to determine if other transport mechanisms at the choroid plexus played a significant role in the removal of VPA from the CNS. In six rabbits, silicone oil was perfused into both cerebral ventricles and out through the cisterna magna to physically block exchange of VPA between cerebrospinal fluid (CSF) and blood and between brain and CSF. In six control rabbits, perfusion was performed with mock CSF. Both groups received a loading dose followed by continuous intravenous infusion of VPA for 210 min. Ventriculocisternal perfusion with silicone oil had no significant effect on the steady-state brain concentrations or brain-to-plasma concentration ratios of VPA, further confirming that efflux of VPA at the choroid plexus is negligible. PMID- 7796792 TI - Chronic administration of sodium valproic acid slows pubertal maturation in inbred DBA/2J mice: skeletal, histological, and endocrinological evidence. AB - Sodium valproic acid (VPA) has been reported to occasionally delay pubertal maturation in children. In the current study, we sought to establish a valid animal model with which to further investigate the neuroendocrinological sequelae of VPA administration. Male and female DBA/2J mice were weaned at 2 weeks of age and administered either VPA (17-20 mg/kg/day) or control solution via drinking water. Animals were weighed and sacrificed via decapitation at 4, 6, or 8 weeks of age. Testes and ovaries were prepared for histological analyses. In addition, the length of the left humerus bone from each animal was obtained as an index of skeletal growth, and trunk blood was assayed for circulating follicle-stimulating hormone (FSH) and prolactin (PRL). For males, testicular weights of the animals receiving VPA were significantly lower than those of control animals at all three sampling ages. No between-group differences were found for body weight at any sampling age, and yet the rate of skeletal maturation (as indexed by humerus length) was decreased significantly for the VPA-treated males at all three sampling periods. Additionally, while hormone levels did not consistently differ, histological analyses of the gonadal tissue demonstrated significantly decreased rats of spermatogenesis at all sampling points for VPA-treated animals. For females, chronic VPA administration led to a significant reduction in uterine weight at the 4 and 6 week sampling periods, and yet by 8 weeks of age the uterine weights for the two groups did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796793 TI - Simultaneous monitoring of the seizure-related changes in extracellular glutamate and gamma-aminobutyric acid concentration in bilateral hippocampi following development of amygdaloid kindling. AB - We simultaneously monitored the seizure-related changes in extracellular hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) concentration in brain dialysates in order to clarify the role of Glu and GABA in the development of kindling. Brain dialysates were collected every 5 min from 10 min prior to 80 min after stimulus in the three developing conditions consisting of pre-kindling state, stage 3 (C-3), and five consecutive stage 5 (5*C-5) following kindling in the same rat. Extracellular Glu level increased rapidly, lasting for only 5 min after stimulus. The post-stimulus ratio of Glu increase in partially kindled rats (C-3) was 2.5-3.5 times of the baseline, and in fully kindled rats it was about 5 times of the baseline. Extracellular GABA concentration enhanced gradually, reaching a plateau level at 15-20 min and lasting for several hours after stimulus at each stage. The enhancement of GABA level was about 1.5 times of the baseline in partially kindled stage, and was about 2.5 times of the baseline in fully kindled stage. There was no significant difference between the two hemispheres with respect to either the time-course or the magnitude of Glu and GABA increase respectively. These data show that progressive, transient and stimulus-induced enhancement of extracellular Glu levels combined with long lasting elevation of extracellular GABA levels in the bilateral ventral hippocampi results in imbalance between the excitatory and inhibitory neuronal systems, causing excessive propagation of seizure activity, culminating in the secondary generalized seizure of amygdaloid kindling. PMID- 7796794 TI - Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. AB - Electrical stimulation of the vagus nerve (VNS) is a new method for the treatment of patients with medically intractable epilepsy. Sixteen patients, ten of whom participated in a larger multicenter double-blind trial on the efficacy of VNS in epilepsy, and six who participated in pilot studies, consented to participate in the present study. Ten patients received HIGH stimulation and six patients LOW stimulation for the 3-month trial. Cerebrospinal fluid (CSF) samples (16 ml) were collected both before and after 3 months of VNS. Amino acid and neurotransmitter metabolites were analyzed. Four patients responded to VS with more than a 25% seizure reduction after 3 months. Mean and median concentrations of phosphoethanolamine (PEA) increased in responders and decreased in nonresponders. Free GABA increased in both groups but more so in the nonresponders. After 9 months of VS (6-9 months on HIGH stimulation) 4 of 15 patients had more than 40% seizure reduction. There were significant correlations between seizure reduction and increases in asparagine, phenylalanine, PEA, alanine and tryptophan concentrations. Comparison between patients with HIGH or LOW stimulation showed a significant increase in ethanolamine (EA) in the HIGH group and a decrease in glutamine in the LOW group. All patients regardless of response or stimulation intensity showed significantly increased total and free GABA levels. A decrease in CSF aspartate was marginally significant. Other trends were decreases in glutamate and increases in 5-hydroxyindoleacetic acid. Chronic VNS appears to have an effect on various amino acids pools in the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796795 TI - The Neurotoxicity Scale: the validity of a patient-based scale, assessing neurotoxicity. AB - The validity of a patient-based scale, presumably measuring adverse effects of drugs on cognitive function, was examined in a normal volunteer study. Thirty subjects were randomly assigned to placebo or one of two doses of a benzodiazepine, temazepam (10 mg and 20 mg), in a double-blind placebo-controlled parallel group design. Plasma samples were taken before the scale was completed and up to 8 hours post-dose. After administration of the medication the subjects were asked to maintain their normal daily routine as much as possible (reading, studying, conversations). The inventory was administered twice, at 50 minutes and 2 hours post-dose (peak level). The overall score was different between the three groups, only for the second assessment, 2 h post-dose (ANOVA, P < 0.02). Multiple t-testing between the three groups revealed statistically significant differences between placebo and the 10 mg temazepam group (P = 0.02) and between placebo and the 20 mg temazepam group (P = 0.006). No significant difference was found between the two temazepam groups. Analysis of the separate questions showed least sensitivity for questions related to the domain of 'hyperexcitability' and most sensitivity for 'fatigue' and 'slowing.' The overall score appeared to be sensitive already for the lower toxicity range suggesting an 'all or nothing effect'. The subjective reports, collected by using this scale, may therefore be used for the detection of gross overall changes in cognitive functioning. PMID- 7796796 TI - Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures. AB - The efficacy and safety of felbamate monotherapy were evaluated in 52 patients with refractory partial seizures with or without secondary generalization in a double-blind, randomized, placebo-controlled trial. Each patient completed a routine evaluation for epilepsy surgery and was randomized to receive either felbamate, titrated to a maximum daily dose of 3600 mg over 2 days, or placebo during the 10-day, inpatient, treatment phase. An intent-to-treat analysis was performed on the data of all 52 patients who received study medication, while a separate efficacy analysis also was performed on the data of 43 evaluable patients, which excluded protocol violators. The endpoint of the trial was completing 10 days of treatment or the occurrence of a fourth seizure. The primary efficacy variable was the average daily seizure frequency during the treatment phase for each patient. For the intent-to-treat analysis based on all 52 patients who received study medications, the mean rank of the daily seizure frequency for patients treated with felbamate was 21.6 compared to 29.6 for patients treated with placebo (P = 0.065). In the analysis based on the 43 evaluable patients, the mean rank of the daily seizure frequency for felbamate treated patients was 17.0 compared to 25.4 for placebo-treated patients. This difference was statistically significant (P = 0.032) in favor of felbamate. Seizure frequency was decreased by 89.5% compared to baseline in nine patients who completed 10 days of felbamate therapy. This study permitted the rapid determination of the anticonvulsant activity of felbamate and demonstrated that felbamate is effective as monotherapy for the treatment of partial seizures. PMID- 7796797 TI - Postictal psychosis: a case control series of 20 patients and 150 controls. AB - We compared clinical data, EEG, and video-EEG studies in a consecutive series of 20 patients with postictal psychosis (PP) to 150 consecutive epilepsy patients with complex partial (CPS) or generalized tonic-clonic (GTCS) seizures but without PP. There was a lucid interval between last seizure and onset of psychosis ranging from 2.3 to 72 h (mean, 25 h). Duration of PP ranged from 16 to 432 h (mean, 83 h). Age, sex, epilepsy type (partial vs. generalized), and history of febrile seizures were similar in the PP and control groups. Patients with PP had more frequent GTCS during monitoring than controls (2.8 vs. 1.3; P < 0.001). Patients with PP were more likely to have a history of encephalitis (P < 0.0001) and psychiatric hospitalization (P < 0.002). More patients with PP had bilateral interictal epileptiform discharges during monitoring than controls (P < 0.0002). Postictal psychosis most often develops in patients with bilateral dysfunction following a cluster of GTCS. PMID- 7796798 TI - Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing. AB - Ciliary neurotrophic factor (CNTF) promotes the survival and differentiation of developing motor neurons and is a potential therapeutic for treating neurodegeneration and nerve injury. The crystal structure of human CNTF has been determined at 2.4 A resolution using multi-wavelength anomalous diffraction (MAD) phasing from a single Yb3+ ions. The structure reveals that CNTF is dimeric, with a novel anti-parallel arrangement of the subunits, not previously observed for other cytokines. Each subunit adopts a double crossover four-helix bundle fold, in which two helices contribute to the dimer interface, whilst two different helices show pronounced kinks. Analysis of the electrostatic surface of CNTF identified residues within these kinked helices that may contact the CNTF receptor-alpha. Solution experiments show that CNTF dimerizes at concentrations > 40 microM. Such dimers are likely to be relevant to the storage of CNTF in the peripheral nerve given the high concentrations present in this tissue. However, it is unlikely that they play a role in engaging the three distinct receptor subunits that comprise the CNTF receptor, given the low concentration of extracellular CNTF and its high potency. PMID- 7796799 TI - Gadolinium-sensitive, voltage-dependent calcium release channels in the endoplasmic reticulum of a higher plant mechanoreceptor organ. AB - The lipid bilayer technique was adapted to the functional reconstitution of ion channels from the endoplasmic reticulum of a higher plant. This was obtained at high purity from touch-sensitive tendrils of Bryonia dioica. In this preparation, a calcium-selective strongly rectifying channel is prevailing whose single channel properties have been characterized. The single-channel conductance is 29 pS in 50 mM CaCl2. The Ca2+: K+ selectivity was determined to be approximately 6.6. The channel is voltage-gated and, more importantly, the gating voltage is strongly shifted towards more negative voltages when a transmembrane Ca2+ gradient is applied. Thus, at physiological voltages across the endoplasmic reticulum membrane, the channel's open probability will be governed largely by the chemical potential gradient of Ca2+, generated by the Ca(2+)-ATPase in that same membrane. The calcium release channel described here is effectively blocked by Gd3+ which also completely suppresses a tendril's reaction to touch, suggesting that this channel could be a key element of calcium signaling in higher plant mechanotransduction. Its molecular characteristics and inhibitor data show it to be the first known member of a hitherto unrecognized class of calcium channels. PMID- 7796800 TI - A new type of signal peptide: central role of a twin-arginine motif in transfer signals for the delta pH-dependent thylakoidal protein translocase. AB - The delta pH-driven and Sec-related thylakoidal protein translocases recognise distinct types of thylakoid transfer signal, yet all transfer signals resemble bacterial signal peptides in structural terms. Comparison of known transfer signals reveals a single concrete difference: signals for the delta pH-dependent system contain a common twin-arginine motif immediately before the hydrophobic region. We show that this motif is critical for the delta pH-driven translocation process; substitution of the arg-arg by gln-gln or even arg-lys totally blocks translocation across the thylakoid membrane, and replacement by lys-arg reduces the rate of translocation by > 100-fold. The targeting information in this type of signal thus differs fundamentally from that of bacterial signal peptides, where the required positive charge can be supplied by any basic amino acid. Insertion of a twin-arg motif into a Sec-dependent substrate does not alter the pathway followed but reduces translocation efficiency, suggesting that the motif may also repel the Sec-type system. Other information must help to specify the choice of translocation mechanism, but this information is unlikely to reside in the hydrophobic region because substitution by a hydrophobic section from an integral membrane protein does not affect the translocation pathway. PMID- 7796801 TI - VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion. AB - VAMP proteins are important components of the machinery controlling docking and/or fusion of secretory vesicles with their target membrane. We investigated the expression of VAMP proteins in pancreatic beta-cells and their implication in the exocytosis of insulin. cDNA cloning revealed that VAMP-2 and cellubrevin, but not VAMP-1, are expressed in rat pancreatic islets and that their sequence is identical to that isolated from rat brain. Pancreatic beta-cells contain secretory granules that store and secrete insulin as well as synaptic-like microvesicles carrying gamma-aminobutyric acid. After subcellular fractionation on continuous sucrose gradients, VAMP-2 and cellubrevin were found to be associated with both types of secretory vesicle. The association of VAMP-2 with insulin-containing granules was confirmed by confocal microscopy of primary cultures of rat pancreatic beta-cells. Pretreatment of streptolysin-O permeabilized insulin-secreting cells with tetanus and botulinum B neurotoxins selectively cleaved VAMP-2 and cellubrevin and abolished Ca(2+)-induced insulin release (IC50 approximately 15 nM). By contrast, the pretreatment with tetanus and botulinum B neurotoxins did not prevent GTP gamma S-stimulated insulin secretion. Taken together, our results show that pancreatic beta-cells express VAMP-2 and cellubrevin and that one or both of these proteins selectively control Ca(2+)-mediated insulin secretion. PMID- 7796802 TI - Targeting of Listeria monocytogenes ActA protein to the plasma membrane as a tool to dissect both actin-based cell morphogenesis and ActA function. AB - Actin assembly on the surface of Listeria monocytogenes in the cytoplasm of infected cells provides a model to study actin-based motility and changes in cell shape. We have shown previously that the ActA protein, exposed on the bacterial surface, is required for polarized nucleation of actin filaments. To investigate whether plasma membrane-associated ActA can control the organization of microfilaments and cell shape, variants of ActA, in which the bacterial membrane signal had been replaced by a plasma membrane anchor sequence, were produced in mammalian cells. While both cytoplasmic and membrane-bound forms of ActA increased the F-actin content, only membrane-associated ActA caused the formation of plasma membrane extensions. This finding suggests that ActA acts as an actin filament nucleator and shows that permanent association with the inner face of the plasma membrane is required for changes in cell shape. Based on the observation that the amino-terminal segment of ActA and the remaining portion which includes the proline-rich repeats cause distinct phenotypic modifications in transfected cells, we propose a model in which two functional domains of ActA cooperate in the nucleation and dynamic turnover of actin filaments. The present approach is a new model system to dissect the mechanism of action of ActA and to further investigate interactions of the plasma membrane and the actin cytoskeleton during dynamic changes of cell shape. PMID- 7796803 TI - The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis. AB - We have prepared a temperature-sensitive Saccharomyces cerevisiae type 2A phosphatase (PP2A) mutant, pph21-102. At the restrictive temperature, the pph21 102 cells arrested predominantly with small or aberrant buds, and their actin cytoskeleton and chitin deposition were abnormal. The involvement of PP2A in bud growth may be due to the role of PP2A in actin distribution during the cell cycle. Moreover, after a shift to the non-permissive temperature, the pph21-102 cells were blocked in G2 and had low activity of Clb2-Cdc28 kinase. Expression of Clb2 from the S.cerevisiae ADH promoter in pph21-102 cells was able to partially bypass the G2 arrest in the first cell cycle, but was not able to stimulate passage through a second mitosis. These cells had higher total amounts of Clb2 Cdc28 kinase activity, but the Clb2-normalized specific activity was lower in the pph21-102 cells compared with wild-type cells. Unlike wild-type strains, a PP2A deficient strain was sensitive to the loss of MIH1, which is a homolog of the Schizosaccharomyces pombe mitotic inducer cdc25+. Furthermore, the cdc28F19 mutation cured the synthetic defects of a PP2A-deficient strain containing a deletion of MIH1. These results suggest that PP2A is required during G2 for the activation of Clb-Cdc28 kinase complexes for progression into mitosis. PMID- 7796804 TI - A pre-start checkpoint preventing mitosis in fission yeast acts independently of p34cdc2 tyrosine phosphorylation. AB - We have monitored the tyrosine (Y15) phosphorylated and dephosphorylated forms of p34cdc2 from Schizosaccharomyces pombe as cells proceed through the cell cycle. Y15 is dephosphorylated in G1 before start and becomes phosphorylated only after cells pass start and enter late G1. This transition is associated with a switch from one checkpoint which restrains mitosis in pre-start G1, by a mechanism independent from Y15 phosphorylation, to a second checkpoint acting post-start during late G1 and S phase operating through Y15 phosphorylation. The pre-start checkpoint may act by preventing formation of the p34cdc2/p56cdc13 complex. The complex between Y15-phosphorylated p34cdc2 and p56cdc13 accumulates during S phase and G2, but the level generated is not solely dependent on the amount of p34cdc2 and p56cdc13 present in the cell. The extent of p56cdc13 breakdown at the end of mitosis may be determined by the amount complexed with p34cdc2. We have also shown that an insoluble form of p34cdc2 is associated with the progression of the cell through late G1 into S phase. PMID- 7796805 TI - Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations. AB - We examined the positive and negative effects of somatic mutation on antibody function using saturation mutagenesis in vitro to mimic the potential of the in vivo process to diversify antibodies. Identical mutations were introduced into the second complementarity determining region of two anti-phosphocholine antibodies, T15 and D16, which share the same germline VH gene sequence. T15 predominates in primary responses and does not undergo affinity maturation. D16 is representative of antibodies that co-dominate in memory responses and do undergo affinity maturation. We previously reported that > 50% of T15 mutants had decreased antigen binding capacity. To test if this high frequency of binding loss was unique to T15 or a consequence of random point mutations applicable to other combining sites, we analyzed the same mutations in D16. We show that D16 suffers a similar loss of function, indicating an equally high potential for B cell wastage. However, only D16 displayed the capacity for somatic mutation to improve antigen binding, which should enhance its persistence in memory responses. Mutation of residues contacting the haptenic group, as determined by molecular modeling, did not improve binding. Instead, productive mutations occurred in residues that either contacted carrier protein or were distant from the antigen binding site, possibly increasing binding site flexibility through long-range effects. Targeting such residues for mutation should aid in the rational design of improved antibodies. PMID- 7796806 TI - An immunoglobulin-like domain determines the specificity of neurotrophin receptors. AB - The neurotrophins influence survival and maintenance of vertebrate neurons in the embryonic, early post-natal and post-developmental stages of the nervous system. Binding of neurotrophins to receptors encoded by the gene family trk initiates signal transduction into the cell. trkA interacts preferably with nerve growth factor (NGF), trkB with brain-derived neurotrophic factor (BDNF) and neurotrophin 4/5 (NT-4/5) and trkC with neurotrophin-3 (NT-3). By constructing 17 different chimeras and domain deletions of the human trk receptors and analyzing their binding affinities to the neurotrophins we have shown that an immunoglobulin-like domain located adjacent to the transmembrane domain is the structural element that determines the interaction of neurotrophins with their receptors. Chimeras of trkC where this domain was exchanged for the homologous sequences from trkB or trkA gained high affinity binding to BDNF or NGF respectively, while deletion of this domain in trkC or trkA abolished binding to NT-3 or NGF respectively. This domain alone retained affinities to neurotrophins similar to the full-length receptors and when expressed on NIH 3T3 cells in fusion with the kinase domain showed neurotrophin-dependent activation. PMID- 7796808 TI - A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. AB - Cytokines manifest their function through alteration of gene expression. However, target genes for signals from cytokine receptors are largely unknown. We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle. To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter. The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation. Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction. PMID- 7796807 TI - The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. AB - Molecular cloning efforts have provided primary amino acid sequence and signal transduction data for a large collection of serotonin receptor subtypes. These include five 5-HT1-like receptors, three 5-HT2 receptors, one 5-HT3 receptor, two 5-HT5 receptors, one 5-HT6 receptor and one 5-HT7 receptor. Molecular biological information on the 5-HT4 receptor is notably absent from this list. We now report the cloning of the pharmacologically defined 5-HT4 receptor. Using degenerate oligonucleotide primers, we identified a rat brain PCR fragment which encoded a '5-HT receptor-like' amino acid sequence. The corresponding full length cDNA was isolated from a rat brain cDNA library. Transiently expressed in COS-7 cells, this receptor stimulates adenylyl cyclase activity and is sensitive to the benzamide derivative cisapride. The response is also blocked by ICS-205930. Interestingly, we isolated two splice variants of the receptor, 5-HT4L and 5 HT4S, differing in the length and sequence of their C-termini. In rat brain, the 5-HT4S transcripts are restricted to the striatum, but the 5-HT4L transcripts are expressed throughout the brain, except in the cerebellum where it was barely detectable. In peripheral tissues, differential expression was also observed in the atrium of the heart where only the 5-HT4S isoform was detectable. PMID- 7796809 TI - The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR interacting protein co-localize at focal adhesions. AB - Focal adhesions are sites of cell-extracellular matrix interactions that function in anchoring stress fibers to the plasma membrane and in adhesion-mediated signal transduction. Both focal adhesion structure and signaling ability involve protein tyrosine phosphorylation. LAR is a broadly expressed transmembrane protein tyrosine phosphatase comprised of a cell adhesion-like ectodomain and two intracellular protein tyrosine phosphatase domains. We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions. Both LAR and LIP.1 decorate the ends of focal adhesions most proximal to the cell nucleus and are excluded from the distal ends of focal adhesions, thus localizing to regions of focal adhesions presumably undergoing disassembly. We propose that LAR and LIP.1 may regulate the disassembly of focal adhesions and thus help orchestrate cell matrix interactions. PMID- 7796810 TI - Pseudosubstrate sequence may not be critical for autoinhibition of smooth muscle myosin light chain kinase. AB - It has been hypothesized that basic residues in the autoinhibitory region of myosin light chain (MLC) kinase, which resemble the substrate sequence, interact with the catalytic core via charge interaction and thus inhibit the kinase activity (pseudosubstrate inhibitory hypothesis). In the present study, we produced seven MLC kinase mutants in which the residues in the autoinhibitory region are deleted to various extents, and determined the residues crucial for the autoinhibition of the kinase activity. The activities of MT799 (1-799) and MT796 (1-796) were completely inhibited, whereas MT793 (1-793), MT791 (1-791), MT787 (1-787) and MT783 (1-783) were constitutively active. The tryptic proteolysis of MT799 and MT796 activated the kinase activity, presumably due to the removal of the residues essential for autoinhibition. The mutants which showed the constitutively active kinase activity were not further activated by tryptic proteolysis, suggesting that the residues crucial for autoinhibition were already deleted. On the other hand, MT795 (1-795) was partially constitutively active (33% of maximum activity) and the tryptic proteolysis further activated the enzyme activity, suggesting that MT795 loses part of the residues essential for autoinhibition. The substitution of the residues Tyr794-Met795 but not Lys793 of untruncated MLC kinase significantly increased the Ca2+/calmodulin-independent kinase activity. These results clearly show that the region Tyr794-Met795-Ala796 is critical for autoinhibition. This study shows that the pseudosubstrate sequence is not critical for the autoinhibition mechanism of MLC kinase. PMID- 7796811 TI - Thrombopoietin activates a STAT5-like factor in hematopoietic cells. AB - Thrombopoietin (TPO) is a newly cloned cytokine which is the major regulator of circulating platelet levels, acting on both proliferation and differentiation of megakaryocytes. We have investigated the ability of TPO to activate the JAK/STAT pathway in megakaryocytic cell lines. We used either the granulocyte-macrophage colony-stimulating factor (GM-CSF)- and/or erythropoietin (EPO)-dependent UT7 cell line in which the murine TPO receptor (mumpl) had been transfected (mumpl UT7 transfectants) or the MO7E and DAMI cells which express endogenous human TPO receptors. We demonstrated that TPO activates the kinase JAK2 and a STAT5-like transcriptional factor but not STAT1, STAT2, STAT3 or STAT4, in a very rapid and transient manner. In order to better ascertain the specificity of the activation of STAT5-related factor by TPO, we investigated the effect of other cytokines/growth factors. Both GM-CSF and EPO activated the STAT5-like factor. In contrast, neither interferon (IFN)-gamma nor the mitogenic stem cell factor (SCF) activated STAT5, although IFN-gamma did activate STAT1 in those cells. The hematopoietic DNA binding activity related to STAT5 was identified as a p97 tyrosine-phosphorylated protein band which exhibited identical gel mobility to the mammary STAT5. Because v-mpl, a truncated form of the TPO receptor c-mpl, was shown to be oncogenic, we tested the activity of v-mpl on STAT5 and found STAT5 constitutively activated in two different v-mpl-expressing cells, the transiently transfected Cos7 cells and the stable v-mpl-UT7 transfectants. Overall, our data indicate that STAT5 is widely expressed in hematopoietic cells and activated by a number of cytokines, including TPO, GM-CSF and EPO, but not by IFN-gamma or SCF. PMID- 7796812 TI - Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. AB - In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects. Loss-of-function alleles result in lethality and underproliferation of diploid tissues of the larva. A dominant gain-of-function allele, Tumorous-lethal (hopTum-l), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hopTum-l mutation. Overexpression of either wild-type hop or hopTum-l in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hopTum-l mutation. In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hopTum-l in Drosophila cell culture results in tyrosine phosphorylation of Hop protein. However, overexpression of hopTum-l results in greater phosphorylation than overexpression of the wild-type. We conclude that hopTum-l encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells. PMID- 7796813 TI - Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B alpha proteolysis and NF-kappa B activation in response to diverse stimuli. AB - Post-translational activation of the higher eukaryotic transcription factor NF kappa B requires both phosphorylation and proteolytic degradation of the inhibitory subunit I kappa B-alpha. Inhibition of proteasome activity can stabilize an inducibly phosphorylated form of I kappa B-alpha in intact cells, suggesting that phosphorylation targets the protein for degradation. In this study, we have identified serines 32 and 36 in human I kappa B-alpha as essential for the control of I kappa B-alpha stability and the activation of NF-kappa B in HeLa cells. A point mutant substituting serines 32 and 36 by alanine residues was no longer phosphorylated in response to okadaic acid (OA) stimulation. This and various other Ser32 and Ser36 mutants behaved as potent dominant negative I kappa B proteins attenuating kappa B-dependent transactivation in response to OA, phorbol 12-myristate 13-acetate (PMA) and tumor necrosis factor-alpha (TNF). While both endogenous and transiently expressed wild-type I kappa B-alpha were proteolytically degraded in response to PMA and TNF stimulation of cells, the S32/36A mutant of I kappa B-alpha remained largely intact under these conditions. Our data suggest that such diverse stimuli as OA, TNF and PMA use the same kinase system to phosphorylate and thereby destabilize I kappa B-alpha, leading to NF kappa B activation. PMID- 7796815 TI - The nucleolar architecture of polymerase I transcription and processing. AB - The nucleolus, the site of transcription and processing of the major ribosomal genes, generally reveals three distinct ultrastructural components in conventional thin-section electron micrographs (fibrillar centres, dense fibrillar component and granular component). We show here that different parts of the transcription and transcript processing pathway can be mapped to the different nucleolar components in pea root cells. This study shows the full three dimensional arrangement of the different domains by in situ hybridization and confocal microscopy, and their correspondence with the major ultrastructural components of the nucleolus is revealed by parallel serial section electron microscopy. The active rDNA is widely dispersed in discrete foci, the larger of which, at least, correspond to well-defined fibrillar centres. A probe to the external transcribed spacer (ETS) sequence of the pre-rRNA transcripts labels clearly demarcated regions surrounding the foci of rDNA, and which we show correspond to the dense fibrillar component. Finally, a probe to the entire 45S transcript shows a higher concentration in regions corresponding to the granular component, surrounding the dense fibrillar component labelled by the ETS probe. The changes in structure that occur with heat shock show that nucleolar organization is dynamic and dependent upon transcriptional activity. These results show that the various RNA processing events are spatially highly organized and suggest a vectorial or radial model of transcription and transcript processing, where nascent and newly completed transcripts occupy zones surrounding the genes, which are in turn surrounded by regions containing the older more mature transcripts. PMID- 7796814 TI - Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. AB - In Drosophila the equalization of X-linked gene products between males and females, i.e. dosage compensation, is the result of a 2-fold hypertranscription of most of these genes in males. At least four regulatory genes are required for this process. Three of these genes, maleless (mle), male-specific lethal 1 (msl 1) and male-specific lethal 3 (msl-3), have been cloned and their products have been shown to interact and to bind to numerous sites on the X chromosome of males, but not of females. Although binding to the X chromosome is negatively correlated with the function of the master regulatory gene Sex lethal (Sxl), the mechanisms that restrict this binding to males and to the X chromosome are not yet understood. We have cloned the last of the known autosomal genes involved in dosage compensation, male-specific lethal 2 (msl-2), and characterized its product. The encoded protein (MSL-2) consists of 769 amino acid residues and has a RING finger (C3HC4 zinc finger) and a metallothionein-like domain with eight conserved and two non-conserved cysteines. In addition, it contains a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions. Males produce a msl-2 transcript that is shorter than in females, due to differential splicing of an intron of 132 bases in the untranslated leader. Using an antiserum against MSL-2 we have shown that the protein is expressed at a detectable level only in males, where it is physically associated with the X chromosome. Our observations suggest that MSL-2 may be the target of the master regulatory gene Sxl and provide the basic elements of a working hypothesis on the function of MSL-2 in mediating the 2-fold increase in transcription that is characteristic of dosage compensation. PMID- 7796816 TI - EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains. AB - Early B cell factor (EBF) was identified and cloned as a transcription factor expressed specifically in B lymphocytes and adipocytes. This protein was also identified as olfactory factor 1 (Olf-1) in olfactory neurons. In this study, we analyzed the structural requirements for DNA binding, homodimerization and transcriptional activation by EBF. A carboxyl-terminal region, containing a repeat of alpha-helices related to the helix-loop-helix motif, is important for dimerization of EBF in solution and can confer dimerization upon a heterologous DNA binding protein. The amino-terminal DNA binding domain by itself is monomeric, but can mediate assembly of dimers on optimized and correctly spaced half-sites. Mutational analysis of the DNA binding domain of EBF indicated that a novel zinc coordination motif consisting of H-X3-C-X2-C-X5-C is important for DNA recognition. Deletion analysis and transfer of regions of EBF onto a heterologous DNA binding domain identified a serine/threonine-rich transcriptional activation domain. Moreover, the DNA binding domain of EBF can mediate transcriptional activation from optimized binding sites. Thus, EBF contains both a complex DNA binding domain that allows for dimerization and transcriptional activation, and additional dimerization and activation domains. PMID- 7796817 TI - Rapid responses to oxidative stress mediated by iron regulatory protein. AB - Reactive oxygen intermediates (ROIs), including superoxide anion (O2.-) and hydrogen peroxide (H2O2), are by-products of aerobic metabolism with potential toxicity towards cellular macromolecules, including lipids, proteins and DNA. Excess ROIs, a condition referred to as oxidative stress, is considered to be a major contributor to ageing, degenerative diseases and reperfusion injury. The reactivity of H2O2 with iron (Fenton reaction) intimately connects oxidative stress and cellular iron metabolism. We have found a novel oxidative stress response pathway in mammalian cells which links oxidative stress to the regulation of iron metabolism. Exposure of cells to H2O2 leads to reduced synthesis of the intracellular iron storage protein ferritin and stimulates transferrin receptor (TfR) mRNA expression. Both responses are post transcriptional and result from induction of iron regulatory protein (IRP) binding to iron-responsive elements (IREs) in ferritin and TfR mRNAs. IRP induction by H2O2 appears to involve the disassembly of its cubane 4Fe-4S cluster and occurs even in the presence of the protein synthesis inhibitor cycloheximide. The induction kinetics by H2O2 far exceed those by iron starvation. The response requires cellular integrity and cannot be elicited in cell extracts. Whereas the activation of IRP by iron depletion is insensitive to okadaic acid, the rapid induction by H2O2 is blocked by this inhibitor of type I/IIa protein phosphatases. Thus okadaic acid separates the activation pathways by iron depletion and oxidative stress, suggesting the involvement of stress-induced kinase/phosphatase pathways in the latter. PMID- 7796818 TI - The 3'-terminal region of the mRNAs for VSG and procyclin can confer stage specificity to gene expression in Trypanosoma brucei. AB - The variant surface glycoprotein (VSG) and procyclin are the respective major surface antigens of the bloodstream and the procyclic forms of Trypanosoma brucei. These proteins and their mRNAs are both the most abundant and absolutely characteristic of their respective life cycle stages. We show that the 3' terminal region of these mRNAs regulates expression of a reporter gene in an inverse manner, depending on the developmental form of the parasite. In the case of VSG mRNA, the 97 nt sequence upstream from the polyadenylation site is responsible for these effects. The regulation occurs through a variation of mRNA abundance which is not due to a change in primary transcription. In the bloodstream form this effect is manifested by an increase in RNA stability, whereas in the procyclic form it seems to be related to a reduction in the efficiency of mRNA maturation. The 3'-end of VSG mRNA can obviate the 5- to 10 fold stimulation of transcription driven by the procyclin promoter during differentiation from the bloodstream to the procyclic form. The predominance of posttranscriptional over transcriptional controls is probably linked to the organization of the trypanosome genome in polycistronic transcription units. PMID- 7796819 TI - Macromolecular recognition through electrostatic repulsion. AB - In the process of genetic translation, each aminoacyl-tRNA synthetase specifically aminoacylates its cognate tRNAs and rejects the 19 other species of tRNAs. A decrease in the specificity of this reaction can result in misincorporations of amino acids into proteins and be deleterious to the cell. In the case of tyrosyl-tRNA synthetase from Bacillus stearothermophilus, the change of residue Glu152 into Ala results in erroneous interactions with non-cognate tRNAs. To analyse how Glu152 contributes to the discrimination between tRNAs by tyrosyl-tRNA synthetase, 11 changes to this residue were created by mutagenesis. The misaminoacylations of tRNA(Phe) and tRNA(Val) with tyrosine in vitro (on a scale going from 1 to 30) and the toxicity of tyrosyl-tRNA synthetase in vivo (on a scale from 1 to 10(7)) increased in a correlated way when the nature of the side chain in position 152 varied from negatively charged to uncharged then to positively charged. The aminoacylation of tRNA(Tyr) was unaffected by the mutations. The results show that the role of Glu152 in the discrimination between tRNAs is purely negative, that it acts by electrostatic repulsion of non-cognate tRNAs and that this mechanism has been conserved throughout evolution. PMID- 7796822 TI - Proceedings from the 2nd International Symposium on Fibrinogen and Cardiovascular Disease. Edinburgh, Scotland, 1-2 November 1994. PMID- 7796820 TI - Site-specific factor involved in the editing of the psbL mRNA in tobacco plastids. AB - In tobacco plastids, functional psbL mRNA is created by editing an ACG codon to an AUG translation initiation codon. To determine if editing may occur in a chimeric mRNA, the N-terminal part of psbL containing the editing site was translationally fused with the aadA and kan bacterial genes. The chimeric constructs were introduced into the tobacco plastid genome by targeted gene insertion. Editing of the chimeric mRNAs indicated that the 98 nt fragment spanning the psbL editing site contains all cis information required for editing. Expression of the chimeric gene transcripts led to a significant decrease in the editing efficiency of the endogenous psbL mRNA. However, the efficiency of editing in the transplastomic lines was unchanged for four sites in the rpoB and ndhB mRNAs. Reduced efficiency of psbL editing, but not of the other four sites, in the transplastomic lines indicates depletion of psbL-specific editing factor(s). This finding implicates the involvement of site-specific factors in editing of plastid mRNAs in higher plants. PMID- 7796821 TI - Type III restriction endonucleases translocate DNA in a reaction driven by recognition site-specific ATP hydrolysis. AB - Type III restriction/modification systems recognize short non-palindromic sequences, only one strand of which can be methylated. Replication of type III modified DNA produces completely unmethylated recognition sites which, according to classical mechanisms of restriction, should be signals for restriction. We have shown previously that suicidal restriction by the type III enzyme EcoP15I is prevented if all the unmodified sites are in the same orientation: restriction by EcoP15I requires a pair of unmethylated, inversely oriented recognition sites. We have now addressed the molecular mechanism of site orientation-specific DNA restriction. EcoP15I is demonstrated to possess an intrinsic ATPase activity, the potential driving force of DNA translocation. The ATPase activity is uniquely recognition site-specific, but EcoP15I-modified sites also support the reaction. EcoP15I DNA restriction patterns are shown to be predetermined by the enzyme-to site ratio, in that site-saturating enzyme levels elicit cleavage exclusively between the closest pair of head-to-head oriented sites. DNA restriction is blocked by Lac repressor bound in the intervening sequence between the two EcoP15I sites. These results rule out DNA looping and strongly suggest that cleavage is triggered by the close proximity of two convergently tracking EcoP15I DNA complexes. PMID- 7796823 TI - Fibrinogen, fibrin and the arterial wall. AB - Virtually all plasma proteins, including fibrinogen, low density lipoprotein and lipoprotein(a), are present in normal arterial intima and in atherosclerotic lesions, and their concentrations are related to plasma concentrations. Fibrin is also a significant component of many lesions, particularly early proliferative (gelatinous) lesions, where it may be muscle cells migrate and proliferate, bind thrombin, and are a source of fibrin degradation products (FDPs), which are mitogenic. Very recent studies suggest that free a-thrombin may be present in lesions despite an apparent excess of antithrombin III, so this may promote fibrin formation within the lesion. Furthermore, fibrinolysis and FDP generation may be mediated by catheptic enzymes in addition to plasmin. PMID- 7796824 TI - Genetic regulation of fibrinogen. AB - Prospective epidemiological studies have shown that elevated levels of fibrinogen are associated with thrombosis and ischaemic heart disease. Several sequence changes in the promoter region of the beta-fibrinogen gene have been detected that are associated with slightly raised plasma fibrinogen levels in healthy, non smoking carriers, but which have much larger genotype-associated effects in smokers. In in vitro assays, these sequence changes affect the binding of liver nuclear proteins and may alter the rate of transcription of the gene and thus the rate of fibrinogen production. One sequence change is close to the consensus sequence for the binding of a nuclear factor responsive to interleukin-6, one of the cytokines responsible for the acute-phase changes seen upon infection or injury. This provides a molecular explanation for the different effects on fibrinogen levels seen in smokers, who are experiencing a 'chronic' and low-grade response to injury. Thus, for elevated plasma fibrinogen, which is associated with a risk of thrombosis, a genetic variation has been detected that determines, in part, its plasma level; but the variability in an individual's response to environmental changes may also be determined in part by their genotype at this locus. In the future, such individual-specific genetic information may be of prognostic and therapeutic use. PMID- 7796825 TI - Fibrinogen and cardiovascular disease: historical introduction. PMID- 7796826 TI - Epidemiology of fibrinogen. AB - As evidence accumulates to implicate fibrinogen as a risk factor for cardiovascular disease (CVD) it becomes important to characterize the levels and correlates of fibrinogen in diverse populations. Knowledge of the correlates of fibrinogen may help researchers to disentangle the independent contribution of elevated fibrinogen concentrations to CVD. Characterization of the normal range and possible determinants of fibrinogen concentrations, likewise, may aid CVD risk assessment and intervention research. Fibrinogen concentrations vary widely among populations and increase with age. Levels are consistently higher in women than men and rise after menopause. Smoking is the most important lifestyle correlate of fibrinogen. People with diabetes and hypertension have elevated fibrinogen levels, as do sedentary and obese individuals. Alcohol intake and oestrogen replacement therapy are associated with lower fibrinogen levels. Most other CVD risk factors are correlated positively with fibrinogen. Fibrinogen is clearly a marker of CVD risk. Yet, the strikingly non-specific pattern of higher fibrinogen with every CVD risk factor suggests that proving an independent causal role of fibrinogen will remain elusive in the absence of trials selectively lowering fibrinogen with the aim of reducing CVD. PMID- 7796827 TI - Recent progress in the pathophysiology of fibrinogen. AB - A great deal of evidence suggests that fibrinogen is implicated in many vascular disorders resulting from atherothrombosis. However, it has not yet been possible either to establish with certainty whether elevated plasma fibrinogen levels cause, or arise as a consequence of, vascular pathology; or to include fibrinogen in the battery of laboratory tests widely used to predict the risk of thrombosis. This article provides an overview of the progress that has taken place in recent years in our understanding of the pathogenetic role of high plasma fibrinogen levels; the identification of genetic markers of atherothrombotic disease; and the clarification of the complex epidemiology of plasma fibrinogen levels as it relates to genotype and environment. The recent improvement in methodology used to measure plasma fibrinogen levels (which should lead to the wider use of fibrinogen assays in clinical practice) is also reviewed. PMID- 7796828 TI - Fibrinogen in ischaemic heart disease. AB - Fibrinogen contributes to both pathological and clinical manifestations of ischaemic heart disease (IHD). Several cross-sectional angiographic studies have shown correlations between the fibrinogen level and the extent of coronary artery disease. The largest of these studies suggests that this relationship is due mainly to luminal occlusion, strengthening the evidence that high fibrinogen levels are thrombogenic. The growing number of prospective studies that have included fibrinogen measurements consistently show a direct, independent and statistically significant association between fibrinogen level and the subsequent incidence of IHD, this association being about as strong as the relation between cholesterol and IHD, for example. The fibrinogen level is also associated with the recurrence of IHD in those who have survived a myocardial infarction and with the onset and recurrence or progression of cerebrovascular disease and lower extremity arterial disease. Besides a contribution to coronary artery changes, high fibrinogen levels predispose to IHD through influences on blood and plasma viscosity, platelet aggregability and the amount of fibrin produced when coagulation is initiated. Progress towards the standardization of methods for measuring fibrinogen increasingly justifies its inclusion in the IHD risk profile. Establishing the value of agents that lower fibrinogen levels is now a high research priority, mainly for clinical reasons but also as part of the evidence for clarifying the nature of the association of raised levels with arterial disease. PMID- 7796829 TI - Fibrinogen and peripheral arterial disease. AB - Both hospital and epidemiological studies have reported elevated plasma fibrinogen levels in patients with intermittent claudication. Fibrinogen levels have also been positively related to the degree of asymptomatic peripheral arterial disease (PAD). In claudicants, raised fibrinogen is predictive of future cardiovascular events, particularly coronary death. These associations between plasma fibrinogen and PAD are independent of diabetes mellitus and serum lipid concentrations. Lifetime cigarette smoking and plasma fibrinogen interact synergistically in their association with PAD. However, most of the increased risk of PAD due to cigarette smoking is not mediated via plasma fibrinogen, and conversely the relationship between fibrinogen and PAD is not wholly dependent on smoking. The association between fibrinogen and PAD is stronger in men than in women, and in women does not occur independently of smoking. When comparing sex differences in a wide range of aetiological factors associated with PAD, plasma fibrinogen is one of the few factors showing a stronger relationship in men than in women, and may be important in explaining sex differences in susceptibility to disease. PMID- 7796830 TI - Fibrinogen and cerebrovascular disease. AB - The importance of fibrinogen has been identified in two prospective observational studies. Reactive elevations in fibrinogen levels that occur within hours of a major stroke invalidate most cross-sectional case-control studies evaluating fibrinogen as a risk factor. However, as no elevation is seen following fresh episodes of transient ischaemic attacks, reliable conclusions drawn from a case control study using such patients support the findings of the prospective studies. The association is related to occlusive stroke, but the relationship with intracerebral haemorrhage is unclear. The relationship has been found to be independent of other haemostatic and haemorheological factors (e.g. von Willebrand factor, tissue plasminogen activator and packed cell volume). Adjustment for regression dilution bias would further strengthen the observed relationship. Therefore, after blood pressure, fibrinogen is the most important potentially treatable risk factor for ischaemic stroke. There are several mechanisms whereby fibrinogen could promote athero-thromboembolism: thrombosis through a hypercoagulable state; the acceleration of atherosclerosis; or the reduction of blood flow due to high blood or plasma viscosity. The mechanism, however, is unlikely to be mediated through high blood viscosity per se as secondary erythrocytosis (another major determinant of blood viscosity) has not consistently been found to be a risk factor for stroke. Studies relating fibrinogen levels to the degree of carotid artery stenosis support the accelerating influence of fibrinogen on atherosclerosis. Fibrinogen should be considered a risk factor for ischaemic stroke and included in the assessment of individual risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796831 TI - Therapeutic interventions to lower plasma fibrinogen concentration. AB - A causal link between plasma fibrinogen levels and the risk of cardiovascular disease is now reasonably well established. Therefore the therapeutic lowering of fibrinogen has become a relevant area of research. Several options to achieve this aim have been reported in the literature. Changes in lifestyle can affect the fibrinogen level, of which smoking cessation is by far the most effective; weight or stress reduction or an increase in regular physical activity may have less pronounced effects; dietary changes appear to have even less effect, though a regular, moderate alcohol consumption may result in a small reduction. Many oral drugs have been shown to lower fibrinogen; however, the data should be viewed critically. In particular, the clinical situation in which a drug is administered must be considered and risk:benefit analyses should be performed before a drug is recommended for this indication. Among the oral fibrinogen lowering drugs, fibrates rank first (e.g. bezafibrate has been reported to reduce increased fibrinogen by as much as 40%, and ticlopidine can induce a reduction of about 15% if fibrinogen was elevated at baseline). Whether concentration within the normal range can be altered by oral medication is less clear. Finally (and obviously), intravenous fibrinolytic agents or heparin-induced extracorporeal low density lipoprotein precipitation will lower fibrinogen dramatically; yet these procedures are rarely indicated for this purpose alone. All options to lower fibrinogen also have prominent effects on other cardiovascular functions; thus, an intervention trial may not be the most appropriate method of testing the validity of the hypothesis of fibrinogen as a cardiovascular risk factor. PMID- 7796832 TI - Recent progress in the clinical aspects of fibrinogen. AB - This article provides an overview of recently accumulated evidence on the pathogenetic role of fibrinogen in various vascular beds; and tries to elucidate determinants for patients' susceptibility so that subgroups at particular risk of severe clinical complications can be characterized more accurately. Based on the considerably elevated risk of cardiovascular complications associated with increased levels of plasma fibrinogen, the potential value of lowering fibrinogen in the primary or secondary prevention of atherosclerotic disease is now recognized as an important topic for consideration. Recent progress in this field will also be reviewed. PMID- 7796833 TI - Biochemistry and measurement of fibrinogen. AB - Fibrinogen is a large heterogeneous family of closely related molecules consisting of three pairs of non-identical polypeptide chains: two A alpha-, two B beta- and two gamma-chains, held together by disulphide bridges. The heterogeneity of fibrinogen is due to heterogeneities in all three chains. Four main types of assay are used to determine fibrinogen:clotting rate (Clauss), clottable protein, precipitation and immunological assays. Heterogeneities may differ from person to person and may affect the apparent fibrinogen concentrations in different assays. A further complicating factor was, until recently, the lack of an international fibrinogen standard. The ratio of Clauss:enzyme immunoassay (EIA) for high + low molecular weight fibrinogen decreases during therapy for acute myocardial infarction and increases again after thrombolytic therapy to above normal values. Furthermore, high molecular weight fibrinogen tends to clot more easily than low molecular weight fibrinogen. This suggests that high molecular weight fibrinogen might be associated with increased thrombotic risk. Fibrinogen assessed by a functional assay (Clauss) alone is strongly associated with ischaemic heart disease. Although not proven, it is conceivable that a fibrinogen with a Clauss:EIA ratio of > 1 has an even stronger association in epidemiological studies. PMID- 7796834 TI - Fibrinogen and cardiovascular disease in clinical practice. AB - Plasma fibrinogen is not measured routinely in clinical practice for prediction of cardiovascular disease (CVD) but further modest advances in the research investigating fibrinogen and CVD may make this a reality. First, agreement must be reached on the most appropriate method of measurement in clinical practice taking account of the type of fibrinogen to be assayed, the sources and degree of measurement variability, the development of standards and the financial costs. Secondly, further information is required on the value of plasma fibrinogen as a useful risk marker in the primary and secondary prediction of future cardiovascular events. There is a need to express risks in a format which is useful to the general public and to clinicians, and which takes account of associated risks of cigarette smoking, blood pressure, and serum lipids. Finally, the effectiveness of lowering plasma fibrinogen levels in patients with CVD is not yet established. Fibrate drugs are warranted in patients with high-risk lipid profiles, but their effects on cardiovascular outcome due to lowering of plasma fibrinogen await the results of current randomized trials. PMID- 7796835 TI - Motor neuron disease and monoclonal gammopathy. AB - In a study to determine the prevalence of monoclonal gammopathy (MG) among patients with motor neuron disease (MND), 6 out of 56 (10.7%) were found to have a monoclonal paraprotein. Of these 6 patients, 4 had an IgG and 2 had an IgA paraprotein. The clinical syndromes consisted of amyotrophic lateral sclerosis in 2 patients, lower motor neuron syndrome with preserved reflexes in at least one limb in 3 patients, and motor neuropathy with multifocal conduction block in 1 patient. The presence of gammopathy appears to correlate with the absence of marked upper motor neuron involvement and with elevated CSF protein concentration. An underlying malignant disorder was ruled out in all 6 patients, and they were considered to have MG of undetermined significance (MGUS). In a control group of 121 age-matched patients with other neuroimmunological disorders, 5 patients (4.13%) had MG. Four of these had gammopathy associated with malignant myeloma, and 1 had MGUS. These results support previous reports of increased prevalence of MGUS in patients with MND and suggest that an autoimmune mechanism may play a role in the disease. PMID- 7796836 TI - Endothelial cell damage in sarcoidosis and neurosarcoidosis: autoantibodies to endothelial cells. AB - Damage to the vascular system, of which endothelial cells are the main constituent, may occur in sarcoidosis. Evidence of blood-brain barrier (BBB) disruption is shown in sarcoidosis with central nervous system (CNS) involvement by means of magnetic resonance imaging or computed tomography. We investigated the presence of antiendothelial cell antibodies by culture of endothelial cells derived from human umbilical cord vein and from human brain using an enzyme linked immunosorbent assay, and the presence of circulating immune complexes using a Raji cell assay, in the sera of patients with sarcoidosis. The patients with sarcoidosis displayed significantly high levels of immunoglobulin G (IgG) binding to endothelial cells after blocking Fc receptor compared to controls (p < 0.01). The sera of neurosarcoid patients with CNS involvement still showed significantly increased levels of IgG binding to brain endothelial cells after blocking Fc receptor compared to controls and those of pulmonary sarcoidosis (p < 0.001 and p < 0.01 respectively). These results suggest that the presence of autoantibodies to endothelial cells may be involved in endothelial cell damage, including BBB disruption. PMID- 7796837 TI - Seronegative chronic relapsing neuroborreliosis. AB - We report an unusual patient with evidence of Borrelia burgdorferi infection who experienced repeated neurologic relapses despite aggressive antibiotic therapy. Each course of therapy was associated with a Jarisch-Herxheimer-like reaction. Although the patient never had detectable free antibodies to B. burgdorferi in serum or spinal fluid, the CSF was positive on multiple occasions for complexed anti-B. burgdorferi antibodies, B. burgdorferi nucleic acids and free antigen. PMID- 7796838 TI - Handling of single brain metastasis. PMID- 7796839 TI - Treatment of amyotrophic lateral sclerosis using a gene therapy approach. AB - Neurotrophic factors which act on motor neurons may provide an efficient treatment for amyotrophic lateral sclerosis. In order to overcome the difficulty of administering proteins into the central nervous system, it is possible to use a gene therapy approach, i.e. the polymer encapsulation of cells which have been genetically engineered to release one of these neurotrophic factors. The polymer encapsulated cells can be implanted subcutaneously or even intrathecally and permit continuous, slow release of proteins. There is no rejection of the cells due to their isolation by a semi-permeable membrane, no risk of tumor formation and the polymer device can be removed in the event of a problem. PMID- 7796841 TI - Spatial and perceptual impairment related to cortical cerebral blood flow and EEG in deep white matter infarcts of the right hemisphere. AB - A study was performed in order to investigate how infarcts located in the white matter of the right hemisphere may affect processing of spatial and perceptual abilities. A battery of neuropsychological tests was applied to 7 right-handed patients with CT-verified infarcts of the right internal capsule or periventricular white matter. Examinations were performed 1-3 weeks post stroke and 3-7 months later. The patients were assessed by neurological examinations, EEG, and cortical regional cerebral blood flow (rCBF) measurements. This study suggested that deep white matter infarcts of the right hemisphere may result in persistent spatial impairment in the absence of decreased cortical rCBF. Perception was disturbed in cases of low mean cortical CBF of both hemispheres. PMID- 7796840 TI - Familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension. AB - Here we review a total of 17 patients, including 4 of our own, with young-adult onset arteriosclerotic leukoencephalopathy, alopecia and lumbago without hypertension. All were Japanese and the illness seemed to be transmitted in an autosomal recessive fashion. The male to female ratio was 7.5:1. The age of onset usually ranged from 25 to 30 years. Acute lumbago, spondylosis deformans, diffuse baldness, and progressive motor and mental deterioration were common clinical features. Cerebral arteriosclerosis and white mater disease were demonstrated pathologically or radiologically. Although the pathogenesis has remained obscure, we think this is a new clinico-pathological entity distinct from the classic type of Binswanger's disease. PMID- 7796843 TI - Neurophysiological and urodynamic examinations in the functional assessment of the spinal cord below the injury site. AB - We examined the characteristics of specific components of the evoked electrospinogram (EESG) in response to tibial nerve stimulation in 28 patients with traumatic injury of the dorsal and cervical spinal cord. The data were correlated with clinical, urodynamic and additional neurophysiological findings. In the majority of patients (82%), 11 with complete and 12 with partial spinal cord lesions, the lumbar components of the EESG were normal. In 4 of these patients with complete lesion above T2 the dorsal EESG was absent. In 5 cases (18%), the lumbosacral EESG was altered in the presence of an atypical clinical syndrome characterized by persistent urinary retention associated with lower leg atrophy and reduced tendon jerks. In these cases, MRI provided evidence of an unexpected sacral lesion. Unlike the dorsal EESG reflecting the afferent dorsal column volley, the lumbar components of the EESG are usually unaffected by interruption of the cord pathways; these last events thus originate from segmental neuronal activity, the involvement of which bears witness to additional lumbosacral damage. PMID- 7796842 TI - Evaluation of influential factors of cognitive impairments in idiopathic Parkinson's disease. AB - Using multivariate analysis, we investigated the influence on cognitive functions of aging, brain atrophy, incidental cerebral hyperintensities (CHs), medication, and severity, duration and the initial symptoms of the disease in 53 patients with idiopathic Parkinson's disease (PD). We semiquantitatively assessed the degree of brain atrophy and CHs based on previously established methods. Cognitive functions were significantly and diffusely impaired in PD when compared with controls who were matched for age as well as for the degree and location of CHs. Patients with PD, however, had larger ventricles. Prefrontal dysfunctions were associated with a variety of predictors such as CHs, brain atrophy, severity of PD and medication whereas dorsolateral frontal functions were related simply to age and CHs in the periventricular region. Posterior brain functions had association with severity of illness, ventricular dilatation and total CH score. Clinically observed cognitive impairments in PD may consist of cognitive defects intrinsic to the disease which are variously modified by these factors. It is essential to consider all these predictors simultaneously in any discussion of cognitive functions in PD. PMID- 7796844 TI - Grades of exophthalmos and thyrotropin-binding inhibitory immunoglobulin in patients with myasthenia gravis. AB - Exophthalmos and thyrotropin-inhibitory immunoglobulin (TBII) were examined in myasthenia gravis (MG) patients with normal thyroid function. Exophthalmos was found in 7 of 31 (22.6%) MG patients, and TBII was detected in 4 of 21 (19.0%) MG patients. The grades of exophthalmos did not decrease after extraocular muscle weakness was improved by treatment. Patients with MG whose diplopia was Tensilon unresponsive were only found among those with exophthalmos. TBII was more frequently detected in MG patients with exophthalmos than in those without. The present study revealed that exophthalmos is not rare in MG patients, even if they do not show any signs of Graves' disease other than exophthalmos and their thyroid functions are within the normal limit. The presence of TBII in MG patients may relate to the development of exophthalmos, and exophthalmos itself might enhance ocular symptoms of MG. PMID- 7796847 TI - Motility pattern of isolated rat proximal colon and excitatory action of neurotensin. AB - The investigation concerned the effects of neurotensin on mechanical activity of isolated rat proximal colon. An isometric-isovolumic preparation was used. Colonic segments showed spontaneous contractile activity, consisting of regular changes in both endoluminal and isometric tension. Neurotensin (1 pM to 0.1 microM) induced a concentration-dependent tonic contraction of both circular and longitudinal muscle accompanied by high frequency oscillatory activity. Desensitization of the neurotensin receptors antagonized the contractile activity of neurotensin. The excitatory effects of neurotensin were partially blocked to the same degree by tetrodotoxin and atropine, indicating that a component of the neurotensin-mediated contraction involves the release of endogenous acetylcholine. The tetrodotoxin-resistant component of the neurotensin-induced effect seems to be due to a direct action on the smooth muscle cells. PMID- 7796845 TI - Strychnine-insensitive glycine site antagonists attenuate a cardiac arrest induced movement disorder. AB - Male Sprague-Dawley rats underwent experimentally induced cardiac arrest and resuscitation, subsequently exhibiting involuntary jerking movements (myoclonus) with salient features similar to the human form of the disorder. The novel strychnine-insensitive glycine site antagonists ACEA-1011 (5-chloro-7 trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-2,3,-dio ne) and ACEA-1021 (5-nitro 6,7-dichloro-quinoxalinedione) significantly attenuated the myoclonus in cardiac arrested rats. (+)-HA-966, (+/-)-HA-966 (3-amino-1-hydroxy-2-pyrrolidinone), and felbamate (2-phenyl-1,3-propanediol dicarbamate) were also effective. Although the drugs vary in their selectivity for strychnine-insensitive glycine sites, they all possess antagonist activity at these sites. Vehicle injections (saline, dimethyl sulfoxide, water) were without effect and no obvious side effects were observed with any of the ligands tested in this study. Since hyperexcitability in the central nervous system is thought to underlie myoclonus, the attenuation of excitatory amino acid neurotransmission through antagonism of strychnine insensitive glycine sites provides a logical mechanism of action for the antimyoclonic effects observed herein. PMID- 7796846 TI - FR144420, a novel, slow, nitric oxide-releasing agent. AB - We report that (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409) decomposes and releases nitric oxide (NO) spontaneously in solution. (+/-)-N-[(E) 4-Ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1- yl]-3- pyridinecarboxamide (FR144420) was synthesized with the aim of discovering a compound with longer duration of effects in vivo, compared with FK409. FR144420, like FK409, released NO spontaneously in solution, but the amount of NO released from FR144420 during a 5-min incubation was half the amount from FK409. In addition, FR144420 spontaneously decomposed and generated nitrite, which is an oxidative metabolite of NO, at half the rate of FK409. In a vasorelaxant study with isolated rat aorta, FR144420 had a weaker potency than FK409 (EC50 = 54 and 8.1 nM, respectively). In in vivo studies, FR144420 decreased mean blood pressure immediately after intravenous and oral administration to conscious rats. The maximum hypotensive effects of FR144420 were less than those of FK409. However, the durations of FR144420-induced (i.v. and p.o.) hypotensive effects were longer than those of FK409-induced effects. In conclusion, FR144420 is more stable and releases NO more slowly in solution than does FK409. In in vivo experiments, FR144420 showed a longer duration of effects than FK409. FR144420 may be very useful for investigating the in vivo actions of NO. PMID- 7796848 TI - A 5-HT3 receptor antagonist fails to prevent cisplatin-induced toxicity in immature rat spinal cord. AB - The use of high doses of cisplatin in treating cancers has been limited by two major adverse effects--emesis and peripheral neuropathies. The emesis has become largely controlled by the introduction of a new class of drugs--the 5-HT3 receptor antagonists. The current study was undertaken to determine if these drugs would also prevent cisplatin-induced neuropathy. We have used a developing rat as an animal model and determined the effects of cisplatin on morphology (loss of spinal cord calcitonin gene-related peptide (CGRP)-containing neurons) and behavior (gait abnormalities and pain perception). Rat pups from the age of 5 days were treated twice weekly for 4 weeks with cisplatin (1 mg/kg), the 5-HT3 antagonist MDL 72222 (3 mg/kg) or both. The animals were tested for pain perception (using tail-flick latencies) at 17 and 21 days of age and for a gait abnormality at 24 days of age. At 34 days of age, the animals were perfused and the lumbar region of the spinal cords stained immunocytochemically for CGRP. Our results show that cisplatin treatment resulted in a dramatic loss of CGRP neurons in the dorsal horn of the spinal cord and a corresponding increase in the animals' threshold for pain. In addition, the animals showed a pronounced gait abnormality, characterized by 'toeing-in'. Treatment with MDL 72222 not only failed to protect against the loss of CGRP neurons but also worsened the gait abnormalities seen after cisplatin treatment alone. These studies confirm and extend the list of morphological and functional adverse effects of cisplatin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796850 TI - The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats. AB - The authors investigated the effects of spinal and supraspinal administration of the benzodiazepine receptor agonist midazolam alone and with opioids on tests of nociception (tail-flick and hot-plate tests) and motor function (catalepsy) in rats. At the spinal level, the dose-response curves for peak effect and area under the curve for morphine were shifted to the left (indicating potentiation) by a submaximal dose of intrathecal (i.t.) midazolam (20 micrograms) in both nociceptive tests. Additionally, 2.5 micrograms of i.t. midazolam, a dose having no effect when given alone, increased antinociception in both tests when given with i.t. morphine. Isobolographic analysis confirmed that i.t. injection of midazolam potentiated antinociception induced by i.t. morphine. At the supraspinal level, intracerebroventricular (i.c.v.) injection of 4 micrograms of midazolam inhibited morphine antinociception, i.e., the dose-response curve for morphine in the hot-plate test shifted to the right. Midazolam did not affect morphine antinociception in the tail-flick test. Catalepsy occurred only when the highest doses of i.t. or i.c.v. morphine or midazolam were injected alone. The differing effect of midazolam on morphine-induced antinociception suggests that different mechanisms are involved in the spinal cord and brain. PMID- 7796849 TI - Hydroxocobalamin and haemoglobin differentiate between exogenous and neuronal nitric oxide in the rat gastric fundus. AB - In longitudinal strips of rat gastric fundus, hydroxocobalamin (30 microM) significantly reduced relaxations to sodium nitroprusside (100 nM), nitric oxide (NO; 5 microM) and S-nitrosocysteine (3 microM), whereas responses to non adrenergic, non-cholinergic (NANC) nerve stimulation were only slightly reduced. The stimulation-induced relaxations were markedly reduced by the NO synthase inhibitor NG-nitro-L-arginine (100 microM). Hydroxocobalamin (30 microM) enhanced relaxations to S-nitrosoglutathione (1 and 3 microM), and had no effect on responses to vasoactive intestinal polypeptide (1 nM). Haemoglobin (10 microM) significantly reduced relaxations to sodium nitroprusside, NO, S-nitrosocysteine and S-nitrosoglutathione, but did not affect responses to NANC nerve stimulation or vasoactive intestinal polypeptide. The results suggest that hydroxocobalamin and haemoglobin can differentiate between exogenous and neuronally released NO, and that the transmitter released from nitrergic nerves in the rat gastric fundus is not free NO or the nitrosothiols, S-nitrosocysteine and S-nitrosoglutathione. PMID- 7796851 TI - Neuronal mechanism of the inhibitory effect of calcitonin on N-methyl-D-aspartate induced aversive behavior. AB - To elucidate the mechanism of antinociceptive effects of calcitonin, we investigated whether receptor antagonists for various neurotransmitter receptors alter the inhibitory effect of calcitonin on intrathecally injected N-methyl-D aspartate-induced aversive behavior in mice. Neither naloxone, an opioid receptor antagonist, phentolamine and benextramine, alpha-adrenoceptor antagonists, nor ritanserin, a 5-HT2A receptor antagonist, inhibited the calcitonin-induced anti aversive effects. Pindolol and (--)-propranolol, non-selective antagonists of beta-adrenoceptors and 5-HT1 receptors, 1-(2-methoxyphenyl)-4-[4-(2-phethalimido) butyl]-piperazine hydrobromide (NAN-190), a 5-HT1A receptor antagonist, 3 tropanyl-3,5-dichlorobenzoate (MDL72222) and metoclopramide, 5-HT3 receptor antagonists, significantly inhibited the calcitonin-induced anti-aversive effects. (--)-Bicuculline, a GABAA receptor antagonist, phaclofen and 5 aminovaleric acid, GABAB receptor antagonists, also attenuated the calcitonin induced anti-aversive effects. These results suggest that beta-adrenoceptor, 5 HT1A, 5-HT3, GABAA and GABAB receptors, but not alpha-adrenoceptor, opioid nor 5 HT2A receptors, are involved in the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice. PMID- 7796852 TI - Dopamine-independent and adenosine-dependent mechanisms involved in the effects of N-methyl-D-aspartate on motor activity in mice. AB - The involvement of dopamine and adenosine mechanisms in the motor effects of systemically administered N-methyl-D-aspartate (NMDA) was studied in non reserpinized and in reserpinized mice. In non-reserpinized mice NMDA induced motor depression (with 8, 25 and 75 mg/kg i.p.) during the first hour and motor activation (with 25 and 75 mg/kg i.p.) during the second hour after its administration. The non-selective adenosine antagonist, theophylline (3, 10 and 30 mg/kg i.p) induced motor activation during both 1-h periods of observation. NMDA-induced motor depression in non-reserpinized mice was antagonized by theophylline. Higher doses of theophylline were needed to counteract the motor depressant effect induced by higher doses of NMDA. The motor activation induced by NMDA and theophylline in non-reserpinized mice was not additive and theophylline did not enhance the motor activation induced by high doses of NMDA. Both NMDA (25 and 75 mg/kg i.p.) and theophylline (10 and 30 mg/kg) induced motor activation in reserpinized mice and, when coadministered, NMDA counteracted the effect of theophylline. NMDA (8 and 25 mg/kg i.p.) antagonized and theophylline (3, 10 and 30 mg/kg i.p.) potentiated the motor activation induced by the non selective dopamine agonist, apomorphine (0.1 mg/kg s.c.), in reserpinized mice. In reserpinized mice, the non-selective dopamine antagonist, haloperidol (0.5 mg/kg s.c.) antagonized the motor activation induced by apomorphine (0.1 mg/kg s.c.) and the induced by theophylline (10 mg/kg i.p.) and did not modify NMDA induced motor activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796853 TI - Histamine chloramines have a persistent stimulating effect on histamine H2 receptors and gastric acid secretion. AB - Histamine plays an important role in the control of gastric acid secretion. Recently, chlorinated derivatives of histamine have been identified as having multiple effects on the intestinal tract. The aim of this study was to investigate the role of histamine chloramines on gastric acid secretion. We compared the effects of histamine and histamine chloramines on the histamine H2 receptors in vitro using guinea pigs and on gastric acid secretion in rats. With respect to the effects on histamine H2 receptors, histamine monochloramine showed agonist effects similar to those seen with histamine, but the agonist effects of histamine dichloramine were about half those of histamine. Unlike histamine effects, the histamine H2 receptor agonist effects of histamine monochloramine and histamine dichloramine did not disappear after repeated washout. With respect to the stimulation of gastric acid secretion in vivo, histamine monochloramine was similar to histamine, while the effect of histamine dichloramine was 42.2 52.7% of that of histamine. The recovery time to the basal secretory level after completion of stimulation by histamine chloramines was significantly prolonged compared with histamine. These results suggest that histamine chloramines, which bind strongly with histamine H2 receptors, may delay the termination of gastric acid secretion and increase the burden on the gastric and duodenal mucosa. PMID- 7796854 TI - Contrasting actions of acute or chronic paroxetine and fluvoxamine on morphine withdrawal-induced place conditioning. AB - The acute and chronic effects of paroxetine and fluvoxamine on naloxone withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluvoxamine (25 mg/kg s.c. given 30 min prior to naloxone withdrawal pairing) and chronic daily paroxetine (10 mg/kg s.c.) coadministration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine (up to 25 mg/kg s.c.) or chronic daily fluvoxamine (10 mg/kg s.c.) coadministration with morphine did not modify subsequent withdrawal place aversion. Previous radioligand binding studies indicate that fluvoxamine has opioid-displacing properties. It is suggested therefore that acute fluvoxamine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine. PMID- 7796855 TI - Beta 2- but not beta 3-adrenoceptors mediate prejunctional inhibition of non adrenergic non-cholinergic contraction of guinea pig main bronchi. AB - We studied the effects of selective beta-adrenoceptor agonists on the cholinergic and non-adrenergic non-cholinergic (excitatory NANC) contractions elicited by electrical field stimulation of guinea pig main bronchi in vitro. Addition of the selective beta 2-adrenoceptor agonists, fenoterol and salbutamol, and the selective beta 3-adrenoceptor agonist, BRL 37344 (4-[2-[(2-hydroxy-2-(3-chlor phenyl)ethyl)amino]-propyl]-phenoxyac etic acid), induced a dose-dependent inhibition of the cholinergic contraction (pD2 7.89, 6.71 and 4.56, respectively) and the excitatory NANC response (pD2 9.11, 8.16 and 7.42, respectively). Fenoterol- and BRL 37344-induced inhibition of the excitatory NANC response was blocked with high potency (pKB 8.77 and 9.07, respectively) by the selective beta 2-adrenoceptor antagonist, ICI 118,511 (erythro-1-(7-methylindan-4-yloxy)-3 (isopropylamino)-but an-2-ol). A comparable contraction induced by neurokinin A (2 or 5 nM) was also inhibited by fenoterol, salbutamol and BRL 37344, but at significantly higher concentrations than for the inhibition of the excitatory NANC response (pD2 8.72, 7.56 and 6.66, respectively). Such a preferential inhibition of electrical field stimulation- versus agonist-induced effects was not observed for cholinergic contractions (pD2 versus methacholine-induced tone 7.86, 6.93 and 5.10, respectively). The results clearly exclude the involvement of beta 3-adrenoceptors in these responses. Furthermore they show that beta 2 adrenoceptors are involved in the prejunctional inhibition of excitatory NANC contractions, presumably via modulation of tachykinin release from sensory nerves, and solely in the postjunctional inhibition of cholinergic contractions. PMID- 7796857 TI - Melatonin improves evening napping. AB - Twelve young adults were treated with either melatonin, 3 mg or 6 mg, or placebo, at two different times before an early evening nap (18.00-20.00 h) according to a balanced double-blind Latin square design. Polysomnographic monitoring revealed that both dosages of melatonin significantly shortened sleep latency and increased total sleep time in comparison to placebo, irrespective of the time of administration. Subjects also tended to assess their sleep as 'deeper' after melatonin treatment. Based on previous data and the present results, it was concluded that exogenous melatonin exerts hypnotic effects only when circulating levels of endogenous melatonin are low. PMID- 7796858 TI - Endothelium-dependent contraction induced by acetylcholine in isolated rat renal arteries. AB - We investigated whether or not acetylcholine elicited an endothelium-dependent contraction and whether an arachidonic acid metabolite was involved in the acetylcholine-induced contraction in ring preparations of rat renal arteries. Acetylcholine (0.1-100 microM) caused a transient contraction in endothelium intact arteries in a concentration-dependent manner. The contraction induced by acetylcholine (10 microM) was enhanced by pretreatment with NG-nitro-L-arginine (100 microM), a nitric oxide synthase inhibitor, and was abolished by mechanical removal of the endothelium. Atropine (0.1 microM), quinacrine (1 and 3 microM), manoalide (0.1 and 1 microM), aspirin (1 and 10 microM), indomethacin (30 and 300 nM), ONO-3708 (9,11-dimethyl-methane-11,12-methano-13,14-dihydro-13-aza-14- oxo 15(beta)-cyclophenyl-omega-pentenor-thromboxane A2 L-arginine salt) (10 nM), S 1452 (calcium (5Z)-1R,2S,3S,4S-7-[3-phenylsulphonyl-aminobicyclo[2.2.1]hep t-2yl] 5- heptenoate hydrate) (3 nM) and SQ29,548 ([1S- [1 alpha,2 beta(5Z),3 beta,4 alpha]]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7 oxabicyclo[2.2.1]hept-2-yl]-5-heptenoi++ + c acid) (3 and 10 nM), but not hexamethonium (1 microM), OKY-046 (sodium (E)-3-[4-(1- imidazolylmethyl)phenyl]-2 propenoic acid hydrochloride monohydrate) (100 microM) and CS-518 (sodium 2-(1 imidazolylmethyl)-4,5- dihydrobenzo[b]thiophene-6-carboxylate) (10 microM) significantly attenuated the acetylcholine (10 microM)-induced endothelium dependent contractions in renal arteries pretreated with NG-nitro-L-arginine. These findings suggest that acetylcholine causes endothelium-dependent contraction by stimulation of muscarinic receptors in rat renal arteries, and that an arachidonic acid metabolite(s) of the cyclooxygenase pathway is involved in this endothelium-dependent contraction. PMID- 7796856 TI - Antagonism of leukotriene responses in human airways by BAY x7195. AB - Contractions induced by leukotriene and anti-IgE (sheep antiserum to human IgE) were antagonized by pretreatment of human airways with the cysteinyl leukotriene receptor antagonist BAY x7195 ((4S)-[4-carboxyphenylthio]-7-[4-(4-phenoxybutoxy) phenyl]-h ept-5-(z)- enoic acid). However, this receptor antagonist did not inhibit either leukotriene D4- or leukotriene C4-induced contractions in human pulmonary veins. The pA2 value for BAY x7195 in human airways against leukotriene D4 was 7.83 +/- 0.16 with a slope of 1.07 +/- 0.15 (means +/- S.E.M; n = 11). The IC50 value for BAY x7195 in human airways contracted with anti-IgE was 0.31 +/- 0.08 microM (n = 11). These results were comparable to those obtained with ICI 204,219 (4-(5-cyclopentyl-oxycarbonylamino-1-methylindol-3-ylmeth yl)-3-methoxy-N otolyl - sulfonylbenzamide). These data demonstrate that BAY x7195 is a potent selective leukotriene receptor antagonist which may block allergic reactions in the lung. PMID- 7796860 TI - Persistence of the effects of ethanol in vitro on the lipid order and enzyme activities of chick-liver membranes. AB - Results demonstrate for the first time that ethanol exerts two different effects on the lipid order of chick-liver mitochondria and microsomes: a fluidizing effect both in the core and at the surface of the membrane, which depends on its physical presence, and a rigidization of the surface of these membranes which occurs after its removal. In addition, and directly related to the reduction in fluidity produced in the membrane surface after ethanol removal, we have detected a persistent alteration in different enzyme activities involved in the hepatic mitochondrial and microsomal electron-transport systems. The persistence of the alterations in the lipid order and enzyme activities may result from a structural rearrangement of the lipid and protein components produced in the lipid bilayer surface when ethanol is no longer present in the membrane. PMID- 7796862 TI - Liver tumour promoting activity of 3,4,5,3',4'-pentachlorobiphenyl and its interaction with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - This study was undertaken to compare the tumour promoting effects induced by 3,4,5,3',4'-pentachlorobiphenyl (PCB 126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition, interactive effects in rats treated with combinations of PCB 126 and TCDD were studied. Partially hepatectomized female Sprague-Dawley rats were initiated with nitrosodiethylamin. After 5 weeks of recovery the promotion treatment started and continued for 20 weeks. The results from the present study demonstrate that PCB 126 elicit approximately 10% of TCDD's tumour promoting activity measured as enhancement of the development of gamma-glutamyl transpeptidase-positive altered hepatic foci in the liver. The factor required for the PCB to match the response of TCDD was adopted as a toxic equivalency factor and was in this case 0.1, which is the same as the factor suggested by Ahlborg et al. (1994). In the groups treated with a mixture of PCB 126 and TCDD the tumour promoting effect indicated an additive response. This result suggests that PCB 126 and TCDD act by the same mechanistical pathway, which in turn, supports that the toxic equivalency factor-concept can be used for TCDD-like tumour promoters. PMID- 7796861 TI - A rat cytomegalovirus infection model as a tool for immunotoxicity testing. AB - A rat cytomegalovirus infection model for use in immunotoxicity testing has been developed. In resistance against viruses, natural killer cells and cytotoxic T cells play an important role. Therefore, this model complements other rat host resistance models for immunotoxicity testing, i.e. existing bacterial and parasitic infection models in which cytotoxic T-cells and natural killer cells play a minor role. Host resistance against cytomegalovirus infections in the rat was determined by titrating infectious virus levels in organs after cytomegalovirus infection in an in vitro infectivity test denoted as the Plaque Forming Unit (PFU) Test. In this test, homogenates of different organs were investigated for infectious virus titers on rat embryonic cell monolayers. We demonstrated that in the salivary gland, the major target organ for rat cytomegalovirus, virus was detectable from 8 days onward after intraperitoneal infection. To show that this model is suitable for the detection of immunotoxicity four different methods for immunosuppression were investigated: 1. gamma-irradiation, 2. congenitally athymic rats, 3. chemically induced immunosuppression, 4. ultraviolet-B (UVB) irradiation. Rat cytomegalovirus titers in the salivary glands of irradiated (500 rad 1 day prior to infection) or congenitally athymic rats were significantly increased as compared to non irradiated rats and euthymic control rats respectively. In TOX-Wistar rats, given 20 or 80 mg bis(tri-n-butyltin)oxide (TBTO) per kg food beginning 6 weeks before cytomegalovirus infection, a regimen known to have immunotoxic effects, cytomegalovirus titers in the salivary glands were significantly increased as compared to non-TBTO-treated cytomegalovirus infected rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796863 TI - Platelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs. AB - In the present study, we asked whether platelet-activating factor (PAF) mediates the ozone-induced increase in airway microvascular leakage. To answer this question, we examined the effect of a PAF receptor antagonist on the ozone induced increase in airway microvascular leakage quantified by the extravasation of Evans blue dye in the guinea pig trachea and main bronchi. Guinea pigs were pretreated with the PAF receptor antagonist, E6123 ((S)-(+)-6-(2-chlorophenyl)-3 cyclopropane-carbonyl-8,11-dimethyl-2,3,4, 5- tetrahydro-8H pyrido[4',3':4,5]thieno[3,2- f][1,2,4]triazolo[4,3-a][1,4]diazepine) (0.01, 0.1 and 1.0 mg/kg i.v.) and then exposed to 3 ppm ozone for 30 min. The PAF receptor antagonist significantly reduced the ozone-induced increase in microvascular leakage in a dose-dependent manner in both the trachea and main bronchi. Our results indicate that PAF mediates the ozone-induced increase in airway microvascular leakage. We therefore suggest that PAF may be involved in ozone induced airway inflammation. PMID- 7796859 TI - Tumor necrosis factor alpha differentially modulates the cellular response of rat hepatocytes in periportal- and pericentral-equivalent cultures. AB - Alterations of cellular functions induced by recombinant human tumor necrosis factor alpha (TNF alpha) were compared in rat hepatocytes cultured under either periportal-equivalent (10 nM insulin; 10 nM glucagon; 13% O2) or perivenous equivalent conditions (10 nM insulin; 1 nM glucagon; 4% O2). TNF alpha induced a time- and dose-dependent increase in nitric oxide (NO) production and an acute phase response (inhibition of albumin secretion and elevation of alpha 2 macroglobulin production) under both culture conditions. NO production was more pronounced in periportal cultures, while the acute phase response was stronger in pericentral cultures. This suggests that NO production and the acute phase response are controlled by different pathways. After exposure to TNF alpha, DNA content was measured fluorimetrically and biochemically. A marked decrease in nuclear DNA content was found exclusively in pericentral cultures after an 8-h exposure, followed by an elevation of lactic dehydrogenase (LDH) release after a 12-h exposure. Aurintricarboxylic acid (100 microM), an inhibitor of endonuclease, significantly inhibited the TNF alpha-induced decrease in nuclear DNA content but only partially inhibited the LDH release. This indicates that the loss of nuclear DNA content in pericentral cultures is due to an activation of endonuclease and the resulting DNA fragmentation and does not correlate with NO production. Furthermore, the release of LDH seems to be only partially associated with DNA damage. Dexamethasone (100 nM) completely inhibited both TNF alpha induced DNA fragmentation and the elevation of LDH release. The results clearly indicate that the toxicity of TNF alpha is influenced by the metabolic state of hepatocytes. Accordingly, the preferential perivenous cell injury observed after exposure to endotoxins in vivo seems to be due to a higher sensitivity of the pericentrally localized hepatocytes towards TNF alpha rather than a TNF alpha concentration gradient. PMID- 7796864 TI - Mechanisms of interleukin-2-induced depression of hepatic cytochrome P-450 in mice. AB - Interleukin-2 (15 micrograms/mouse, i.p. twice daily for 4 days and once on the 5th day) significantly lowered cytochrome P-450 and heme content and increased heme oxygenase mRNA accumulation; the activities of 7-ethoxycoumarin O deethylase, ethoxy- and pentoxyphenoxazone O-dealkylases were decreased. The activity of the type O form of hepatic xanthine oxidase increased, but there was no increase in lipid peroxide, expressed in terms of microsomal malondialdehyde. In vivo inactivation of xanthine oxidase activity by feeding mice with tungstate did not substantially change the degree of interleukin-2-induced cytochrome P-450 depression, suggesting that the two processes are not causally linked. Induction of tolerance to endotoxin by a 4-day pretreatment with lipopolysaccharide resulted in 50% protection against this depression despite inhibition of the interleukin-2 induced formation of tumor necrosis factor. This suggests that the release of tumor necrosis factor per se does not fully account for the depression of cytochrome P-450. Dexamethasone, already used in patients to reduce the toxicity of interleukin-2 therapy, provided full protection against the cytochrome P-450 depression. PMID- 7796865 TI - Relaxation of rat thoracic aorta induced by pyridine. AB - The pharmacological and toxicological activity of pyridine was determined in rat thoracic aorta. Pyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of pyridine and this relaxing effect was not affected by indomethacin (20 microM), NG-monomethyl-L-arginine acetate (50 microM) or methylene blue (50 microM). In high-K+ medium (80 mM), pyridine inhibited the Ca2+ concentration-dependent vasocontraction. Moreover, in Ca(2+)-free medium, the norepinephrine (3 microM)-induced phasic contraction was also suppressed by pyridine, while the caffeine (10 mM)-induced contraction remained unaffected. The cAMP and cGMP levels of rat aorta were not changed by pyridine. The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by pyridine in a concentration-dependent manner. All of these findings indicated that pyridine relaxes rat thoracic aorta by virtue of its Ca2+ channel-blocking properties in vascular smooth muscle. PMID- 7796866 TI - Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischemic rat hearts. AB - The aim of the present study was to examine the effects of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mitochondrial respiration in ischemic rat hearts, and to compare the effects between water soluble pravastatin and lipid-soluble simvastatin. Either vehicle (0.5% carboxymethyl cellulose), pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Ischemia was induced by ligating the aorta for 60 min in anesthetized open chest rats under artificial respiration. The hearts were removed, mitochondria were isolated, and the respiration was determined by polarography using glutamate and succinate as substrates. When succinate was used as a substrate, the ADP-stimulated respiration (QO3) and ATP production per unit oxygen (ADP/O ratio) were decreased by ischemia. The decreases in QO3 and ADP/O ratio in the pravastatin- and simvastatin-treated groups appeared to be more prominent than those in the vehicle-treated group. This was especially true in the simvastatin-treated group. The ADP-limited respiration (QO4) with succinate in the vehicle-treated heart was slightly increased by ischemia, while that in the pravastatin- or simvastatin treated hearts was decreased. In conclusion, HMG-CoA reductase inhibitors may result in worsening of myocardial mitochondrial respiration during ischemia. PMID- 7796867 TI - Modulation of TCDD-induced wasting syndrome by portocaval anastomosis and vagotomy in Long-Evans and Han/Wistar rats. AB - Portocaval anastomosis and vagotomy operations were performed in Long-Evans (L-E) and Han/Wistar (H/W) rats to elucidate the mechanism of anorexia induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). TCDD-sensitive L-E rats were given a sublethal (5 micrograms/kg) or a lethal dose (20 micrograms/kg) by gavage 5-8 weeks after portocaval anastomosis. TCDD-resistant H/W rats were given a nonlethal dose (500 or 7200 micrograms/kg). The shunt operation did not reduce lethality from TCDD. The effect on wasting of the marginally toxic dose of 5 micrograms/kg in L-E rats was potentiated by the portocaval operation, and the lethal dose was effective in both shunted and sham-operated L-E rats. TCDD failed to decrease food intake and body weight in shunted rats of H/W strain at either dose level though it did so in sham-operated controls. The lack of effect may be due to the already reduced weight of shunted rats at the time of TCDD dosing. TCDD anorexia was not explained by changes in histamine or serotonin (5-HT) turnover in the brain. Vagotomy did not influence lethality after TCDD, although reduction in food intake was somewhat blunted in H/W rats. The results seem to indicate that the anorectic effect of TCDD is modified when portal blood bypasses the liver. The mechanisms remain to be elucidated in detail, but the results do not favor the role of liver as the only or the major initiator of TCDD anorexia. Little evidence was found to support a crucial role of vagal afferent input. PMID- 7796868 TI - Nanomolar concentrations of ouabain block ethanol-inducible Na+,K(+)-ATPase activity in brain. AB - The effect of low concentrations of ethanol on Na+,K(+)-ATPase activity, defined as ouabain-inhibitable 86Rb+ (K+) uptake, was investigated in a crude synaptosome preparation which was subject to minimal subcellular fractionation procedures. Moderate (20-30%) but potent (EC50 = 3.8 mM) stimulation of total ouabain (1 mM) inhibitable K+ uptake by ethanol was observed following incubation periods of up to 20 min. The activity of the ethanol-induced component of K+ uptake was antagonized by nanomolar concentrations of ouabain. Thus, the moderate stimulation of total ouabain-inhibitable K+ uptake by ethanol was attributable to the activation of a component of K+ uptake which was very sensitive (VS; IC50 = 2.8 x 10(-10) M) to inhibition by ouabain. Slightly higher concentrations of ouabain (10(-9) - 10(-6.6) M) stimulated K+ uptake above control (no ethanol or ouabain) in both the absence and presence of ethanol. The selectivity of the VS ethanol interaction was demonstrated by the lack of any ethanol effect on two other components of ouabain-inhibitable K+ uptake which accounted for inhibition of K+ uptake by concentrations of ouabain above 10(-6.6) M and were defined as sensitive (S; IC50 = 10(-6) M) and insensitive (I; IC50 = 10(-4) M) to ouabain. These results define the ethanol-inducible component of ouabain-inhibitable Na+,K(+)-ATPase activity and promote the view that changes in Na+,K(+)-ATPase dependent ion translocation may contribute to ethanol intoxication in vivo. PMID- 7796869 TI - Pertussis and cholera toxins modulate kappa-opioid receptor agonists-induced hypothermia and gut inhibition. AB - In mice pretreated intracerebroventricularly (i.c.v.) with either saline (10 microliters/mouse), pertussis (1 microgram/mouse) or cholera (2.5 micrograms/mouse) toxins, effect of kappa-opioid receptor agonists on the colonic temperature and charcoal meal transit time were assessed. The kappa-opioid receptor agonist, trans-(+)-3,4-dichloro-N-methyl-[2-(1- pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate hydrate (U-50488H, 50, 100 and 200 micrograms/mouse, i.c.v.) produced dose dependent hypothermia. Pertussis toxin pretreatment (72 and/or 144 h before) antagonized (P < 0.05) the hypothermic effect of U-50488H (100 micrograms/mouse) and (+)-trans-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl[benz[b]-thio-phene-4-acetamide (PD 117302, 30 micrograms/mouse). In contrast, cholera toxin pretreatment (48 and/or 96 h before) did not antagonize the hypothermic effect of the kappa-opioid receptor agonists. Moreover, both i.c.v. and intrathecal (i.t.) administration of kappa opioid receptor agonists, U-50488H, }[5R-(5 alpha,7 alpha,8 beta)]-(+/-)-N-methyl N-[7-(1- pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]-benzeneacetamide? (U-69593) and PD 117302, produced dose dependent inhibition of the charcoal meal transit. Cholera toxin pretreatment (48 and 96 h before) augmented (P < 0.05) the antitransit effect of i.c.v. administered U-50488H (100 micrograms/mouse), U 69593 (100 micrograms/mouse) and PD 117302 (50 micrograms/mouse). However, pertussis toxin pretreatment did not affect the gastrointestinal inhibitory effect of the kappa-opioid receptor agonists. The present results extend our previous results on the effect of kappa-selective agonists on gastrointestinal motility and indicate, like the prototype opiate agonist morphine, kappa-opioid receptor agonists are effective in inhibiting the gastrointestinal motility when administered either by intrathecal or intracerebroventricular routes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796870 TI - Possible involvement of Ca(2+)-induced Ca2+ release mechanism in Ag(+)-induced contracture in frog skeletal muscle. AB - To determine if an Ag(+)-induced contracture is associated with the Ca(2+) induced Ca2+ release mechanism in the sarcoplasmic reticulum, effects of Ca(2+) induced Ca2+ release modulators on the Ag(+)-induced contracture were studied with single fibers of frog toe skeletal muscle. The fiber treated with 1 mM caffeine contracted significantly much more than controls without caffeine at Ag+ concentrations below 1 microM. Procaine shifted the Ag+ concentration-tension curve to the right, dose-dependently. When 10 mM procaine was applied to contracting fibers not treated with caffeine, the duration of 5 microM Ag(+) induced contracture was shortened with a little decrease in tension amplitude, that was different from the effect of procaine on caffeine contracture. In caffeine solution, 0.5 microM Ag+ caused a long-lasting contracture with sometimes two peaks. 2 mM procaine led to disappearance of such two peaks, resulting in shortening of the contracture. K+ contracture was potentiated by 1 mM caffeine only at lower concentrations of K+, and inhibited by 10 mM procaine. These results suggest that the Ag(+)-induced contracture is composed of two components: Ca(2+)-induced Ca2+ release-dependent and -independent. 5 microM Ag(+)-induced contracture slowly relaxed with a wavy tension pattern to the resting level when 0.05 mM dithiothreitol was applied around peak of the tension. This relaxation was accelerated by procaine application. These findings may be explained by attributing a portion of Ag(+)-induced contracture to the effect of Ca2+ released through the Ca(2+)-induced Ca2+ release mechanism in the sarcoplasmic reticulum. PMID- 7796872 TI - Antagonism by paraquat of the relaxing effects of acetylcholine and A23187 in rat thoracic aorta. AB - Paraquat, a widely used herbicide, has been reported to be capable of producing superoxide. In the present paper, therefore, the possibility of paraquat inhibiting endothelium-dependent relaxation, mediated by the production of nitric oxide, was tested. The relaxing effects of acetylcholine and A23187, but not that of sodium nitroprusside, in the rat thoracic aorta were found to be inhibited by paraquat in a concentration-dependent manner. In contrast, paraquat was totally inactive with regard to the aortic contractions induced by either norepinephrine or prostaglandin F2 alpha. The inhibitory action of paraquat could be antagonized by superoxide dismutase but not by catalase and indomethacin. All of these findings indicate that superoxide anions produced by paraquat in the endothelium contribute to a decrease in the relaxation response to acetylcholine and A23187 by interfering with endothelium-derived nitric oxide. PMID- 7796871 TI - The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins. AB - This study defined the ability of a large sample of heterogeneous pesticides and neurotoxins to interact with the [3H]tyramine-labelled vesicular transporter of dopamine in rat striatum. Botanical (with rotenone as the most potent), and organochlorine (Kepone) insecticides, as well as fungicides (Zineb), as a whole, consistently inhibited [3H]tyramine binding, with Ki values ranging from 5 nM to 10 microM. ATP/Mg(2+)-dependent [3H]tyramine uptake to purified striatal synaptic vesicles was also inhibited by rotenone. Organophosphate and carbamate insecticides, and miscellaneous herbicides poorly antagonized [3H]tyramine binding, yielding Ki values exceeding 10 microM. Several, though not all, of the best recognized central neurotoxins tested were major binding antagonists. Their rank order of potency was 1-methyl-4-phenylpyridinium ion (MPP+) > trimethyltin > or = 6-hydroxydopamine > N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) > 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with Ki values ranging from 35 nM to 3 microM. Overall, the potent interaction of selected pesticides and chemicals with the vesicular transporter for dopamine, although, by itself, not synonymous with neurotoxicity, would argue for a likely impairment of transmitter homeostasis, or the putative formation of neurodegenerative toxin pools. PMID- 7796873 TI - Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine. AB - The enzymes of mitochondrial respiratory chain, NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV), were completely inhibited by 6 hydroxydopamine with IC50 = 10.5 microM and IC50 = 34 microM respectively. The enzyme inhibition was insensitive to the change of NADH or cytochrome c concentrations. The extent of complex I inhibition decreased as a consequence of both non-enzymatic and monoamine oxidase-catalyzed oxidation of 6 hydroxydopamine. Monoamine oxidase A and B inhibitors, tranylcypromine and clorgyline but not l-deprenyl increased the extent of 6-hydroxydopamine induced inhibition of complex I. Thus, 6-hydroxydopamine itself and not its oxidation products may be responsible for the neurotoxicity of this agent via inhibition of respiratory chain enzymes. PMID- 7796874 TI - N-acetylcysteine protects against age-related decline of oxidative phosphorylation in liver mitochondria. AB - Since it has been proposed that oxygen radical inactivation of key enzymes plays a critical role in cell aging, we have investigated the effects of a thiolic free radical scavenger on the oxidative phosphorylation enzymes of liver mitochondria from female OF-1 mice. At 48 weeks of age a control group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of N acetylcysteine. A 24-week treatment resulted in a significant increase in the specific activities of complex I, IV and V in the hepatic mitochondria of the N acetylcysteine-treated animals as compared to aged controls. PMID- 7796876 TI - Effect of N-acetyl-L-cysteine on sepsis in mice. AB - The effect of the antioxidant N-acetyl-L-cysteine was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. N Acetyl-L-cysteine significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of N-acetyl-L-cysteine was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that N-acetyl-L cysteine works as a direct antioxidant and scavenger of free radicals generated from other sources. PMID- 7796875 TI - Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes. AB - The effects of free radicals on voltage-gated Ca2+ currents (ICa) were investigated in single guinea-pig ventricular myocytes using the whole-cell clamp technique. ICa was measured in the baseline state and after the application of free radicals from cumene hydroperoxide or generated from the addition of purine to xanthine oxidase. ICa decreased from 846 +/- 533 (S.D.) pA to 688 +/- 444 pA (n = 7, P < 0.05) in the presence of 100 microM cumene hydroperoxide and from 708 +/- 157 pA to 457 +/- 163 pA (n = 5, P < 0.0001) in the presence of 500 microM cumene hydroperoxide. ICa also decreased from 1303 +/- 560 pA to 965 +/- 360 pA in the presence of the free radical generating system (2.3 mM purine plus 20 U/l xanthine oxidase). The reduced ICa could not be restored by washing for up to 5 min using normal recording solution. We conclude that ICa is decreased in the presence of cumene hydroperoxide and an oxygen-derived free radical generating system in single guinea-pig ventricular myocytes. The cellular Ca2+ overload observed in free radical mediated reperfusion injury is therefore unlikely to result from an increase in sarcolemmal Ca2+ entry via voltage-gated Ca2+ channels. PMID- 7796877 TI - Origins and developmental potential of the neural crest. AB - Neural crest cells are a migratory population that forms most of the peripheral nervous system, facial skeleton, and numerous other derivatives. These cells arise from the neural ectoderm and are first recognizable as discrete cells after neural tube closure. In this review, I summarize the results of studies from our laboratory on neural crest cell lineage and origin. Our recent experiments demonstrate that interactions between the presumptive neural plate and the nonneural ectoderm are likely to be instrumental in the induction of the avian neural crest. Juxtaposition of these tissues at early stages results in the formation of neural crest cells at the interface. However, neural crest cells do not appear to be segregated from other neuroepithelial cells; cell lineage studies have demonstrated that individual precursor cells within the neural tube can give rise to both neural crest and neural tube derivatives as diverse as sensory, commissural, and motor neurons. This suggests that individual neuroectodermal cells are multipotent, such that a precursor within the neural tube has the ability to form both neural tube (central nervous system) and neural crest (peripheral nervous system and other) derivatives. Further support for flexibility in the developmental program of neuroepithelial cells comes from experiments in which the cranial neural folds are ablated; this results in regulation by the remaining ventral neural tube cells to form neural crest cells after the endogenous neural crest is removed. At later stage of development, this regulative capacity is lost. Following their emigration from the neural tube, neural crest cells become progressively restricted to defined embryonic states. Taken together, these experiments demonstrate that: (1) the neural crest is an induced population that arises by interactions within the ectoderm; (2) initially, progenitor cells are multipotent, having the potential to form multiple neural crest and neural tube derivatives; and (3) with time, the precursors become progressively restricted to form neural crest derivatives and eventually to individual phenotypes. PMID- 7796878 TI - Differentiation capacity toward mesenchymal cell lineages of bone marrow stromal cells established from temperature-sensitive SV40 T-antigen gene transgenic mouse. AB - Stromal cell lines were established from bone marrow of temperature-sensitive T antigen gene transgenic mice. These stromal cell lines consisted of fibroblasts, endothelial cells, and preadipocytes. We found that these stromal cell lines exhibited phenotypic changes depending on the inactivation of T-antigen and growth condition; one preadipocyte line was induced toward adipocytes and osteogenic cells, and several preadipocyte and endothelial cell lines were induced toward muscle cells and adipocytes. Some cell lines showed bipotential characters. These results indicated that stromal cells consisting of bone marrow hematopoietic microenvironment are derived from multipotent mesenchymal stem cells. PMID- 7796879 TI - Changes in protein kinase C isoenzyme expression associated with apoptosis in U937 myelomonocytic cells. AB - Spontaneously apoptotic U937 cells from exponentially growing cell cultures were enriched on discontinuous Percoll density gradients. Increased PKC-beta and reduced PKC-zeta expression were detected in apoptotic cells by Western blotting. Using confocal microscopy, changes in the level of PKC isoenzymes were confirmed and in addition alterations in the subcellular location of PKC isoenzymes were detected in apoptotic cells compared with nonapoptotic cells. The data indicate that the expression of specific PKC isoenzymes is modulated during apoptosis and that PKC-beta and PKC-zeta may play specific roles in the regulation of the apoptotic program. PMID- 7796880 TI - A novel protein expressed in mammalian cells undergoing apoptosis. AB - Human and rodent cells undergoing apoptosis were observed to express high levels of a novel 45,000 M(r) protein. The protein, which we have termed apoptosis specific protein (ASP), was found in Burkitt lymphoma (BL) cells and in adenovirus-transformed human and rat embryo cells induced into apoptosis by a variety of stimuli, including serum deprivation, exposure to the Ca2+ ionophore, ionomycin, treatment with inhibitors of macromolecular synthesis (cycloheximide and actinomycin D), and cold shock. In BL cells treated with apoptotic stimuli, expression of the oncoprotein Bcl-2 was found to both protect from apoptosis and prevent expression of ASP. ASP was not detected either in viable cells or in cells dying passively by necrosis. Laser scanning confocal microscopy showed high levels of ASP in the cytoplasm of cells displaying the chromatin condensation and fragmentation patterns typical of apoptosis. Retention of ASP was observed even when DNA was no longer detectable, and two-color immunofluorescence staining indicated that the protein primarily colocalized with, but was clearly distinct from, non-muscle actin. These findings, together with the observation that biochemical extraction of ASP was only possible under conditions which caused solubilization of the cytoskeleton, leads us to conclude that ASP forms part of, or at least strongly associates with, a modified cytoskeleton unique to cells undergoing apoptosis. While elucidation of its function will require further work, ASP constitutes a powerful marker for the diagnosis and quantitation of apoptosis in vivo and in vitro. PMID- 7796882 TI - Pamlin, a primary mesenchyme cell adhesion protein, in the basal lamina of the sea urchin embryo. AB - Pamlin, a primary mesenchyme cell (PMC) adhesion protein, was isolated from the blastocoel of embryos of the sea urchin Hemicentrotus pulcherrimus. PMCs isolated from mesenchyme blastulae bound exclusively to pamlin. Pamlin is a distinctive extracellular matrix (ECM) component from reported ECM molecules in sea urchin embryos in its motility on SDS-PAGE gels both with and without 2-mercaptoethanol and histological localization. A monoclonal antibody was raised against pamlin, and this protein was immunoaffinity purified. The Mr of pamlin shown by SDS-PAGE gel analysis under nonreduced conditions was 255 kDa. Under reduced conditions, pamlin was cleaved to 180-, 52-, and 23-kDa subunits, indicating the 255-kDa protein is an SS-bonded heterotrimer. PMCs bound exclusively to the 52-kDa subunit. Mannose residues occur in the larger two subunits, but not in the smallest subunit. Pamlin does not run into 4% nondenatured PAGE gels, suggesting that the native glycoprotein forms a large polymeric supramolecular configuration in vivo. Immunohistochemistry showed that pamlin is seen on the entire basal lamina in the blastocoel and hyaline layer of mesenchyme blastulae. In vitro PMC migration assays on pamlin show that an optimum amount of pamlin for PMC migration was 2.5 micrograms/ml and that a synthetic RGDS peptide inhibited PMC migration dose dependently. PMID- 7796881 TI - The glucagon gene is transcribed in beta-like pancreatic cells. AB - In this report we demonstrate that approximately 1.1 kb of the rat glucagon gene promoter upstream of the transcriptional start site specifically directs the transcription of the reporter gene chloramphenicol acetyl transferase (CAT) (p[ 1.1]GLU-CAT) in insulinoma beta-TC1 cells. On the contrary, the 350 bp closest to the transcription start site (p[-0.35]GLU-CAT) are ineffective in beta-TC1 cells. Both constructs are transcriptionally active in InR1-G9 glucagonoma cells. While protein kinase A and protein kinase C activators, acting through independent pathways, strongly increase both the transcription of p[-1.1]GLU-CAT and the accumulation of glucagon transcript in beta-TC1 cells, they are weaker activators in InR1-G9 cells. Our experiments suggest that some positive transcription control elements, necessary for the glucagon gene transcription in insulinoma beta-TC1 cells, are localized in the -350/-1100 region of the glucagon gene. Furthermore, our data indicate that glucagon gene transcription can be strongly activated through the protein kinase A pathway in some specific cellular contexts. PMID- 7796883 TI - A monoclonal antibody raised against rat ovarian antigen recognizes Leydig cell surface: an immunocytochemical study. AB - Using a monoclonal antibody (Mab) against constituents of rat ovarian granulosa cells, we found a 59-kDa protein located on the plasma membrane of a number of granulosa cells in follicles at different stages of development. This Mab (5G5) was found to bind to Leydig cells in rat male gonads. The localization of the antigen, recognized by Mab 5G5 in rat testis, was studied by light and electron microscopic immunocytochemistry (ABC method and IGS technique). Even though Sertoli cells in male gonads are regarded as the counterpart of granulosa cells in ovaries, the results of the experiments described here do not allow such an interpretation because staining with this antibody was restricted to the Leydig cell surface. The immunoreactivity in testicular sections from immature rats was similar to that found in adult testicular tissue. Our immunocytochemical results indicate that the plasma membrane of Leydig cells in rat male gonads shares certain biochemical and molecular properties with rat ovarian granulosa cells. On the basis of the immunocytochemical studies reported here, we suggest that the antigen recognized by Mab 5G5 may be common to all rat steroidogenic organs. Further studies are needed to establish the identity of the antigen in Leydig cells as well as its site of synthesis and its site of action. Thus, Mab 5G5 appears to hold significant potential as a powerful tool for future investigations. PMID- 7796884 TI - Apoptosis is induced in BHK cells by the tsBN462/13 mutation in the CCG1/TAFII250 subunit of the TFIID basal transcription factor. AB - A temperature-sensitive (ts) mutant of the BHK21 cell line derived from golden hamsters, tsBN462 has a mutation in the gene encoding the largest subunit of the TFIID complex, TAFII250/p230/CCG1, and arrests in the G1 phase at the nonpermissive temperature, 39.5 degrees C. We found that tsBN462 cells underwent apoptosis following growth arrest at 39.5 degrees C, suggesting a role for CCG1 as a repressor of apoptosis. By electron microscopic observation, tsBN462 cells at 39.5 degrees C showed characteristic features of apoptosis. Apoptosis was not suppressed by expression of Bc1-2 or the adenovirus E1B 19 kDa protein. Cell death was suppressed completely by expression of wild-type CCG1 and partially by wild-type p53, a growth suppressor protein. Cell cycle arrest induced by p53 may help survival of tsBN462 cells at 39.5 degrees C. Apoptosis was accelerated in SV40 large T antigen-transformed tsBN462 cells at 39.5 degrees C where SV40 large T antigen formed a complex with p53, implying that the apoptosis of tsBN462 cells at 39.5 degrees C occurred in a p53-independent manner. Our results suggest that CCG1/TAFII250 is required for the expression of factors regulating apoptosis. PMID- 7796885 TI - Characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes (HPV-E6E7 ORFs). AB - Primary human ovarian surface epithelial (HOSE) cells were immortalized by a retroviral vector (LXSN-16E6E7) expressing HPV-E6E7 open reading frames (ORF). Immortalizations of primary ovarian epithelial cells were achieved in three of three attempts. Detailed analysis was carried out in one line, HOSE 6-3, selected on the basis of its epithelial morphology. The immortalized line (HOSE 6-3) was nontumorigenic in nude mice when examined at subculture number 20. Cytogenetic analysis confirmed its human origin and detailed karyotypic analysis revealed a mixed karyotype made up of about 60% of diploid and 40% of near-tetraploid cells. Clonal chromosomal aberration was observed in a subpopulation of cells involving a ring chromosome number 9. Immunofluorescence and two-dimensional gel electrophoresis revealed the presence of vimentin and several species of cytokeratin (K7, K8, K18, K19). The profile of the cytoskeletal filaments of HOSE 6-3 cells is largely identical with that of normal ovarian epithelial cells before immortalization. The immortalized ovarian epithelial cells have a lower sensitivity to TGF-beta 1 inhibition compared to normal ovarian epithelial cells. The immortalized line, HOSE 6-3, has altered growth properties including a higher proliferation rate, plating efficiency, and saturation density. The establishment of a continuous line of human ovarian epithelial cells may provide an in vitro model for study of carcinogenesis in human ovarian cancers. PMID- 7796886 TI - Constitutive production of 92-kDa gelatinase B can be suppressed by alterations in cell shape. AB - We have examined the effect that cell shape has on production of the 92-kDa gelatinase B, an enzyme of the matrix metalloproteinase family thought to contribute to the invasiveness of both normal and malignant cells. Using the agent poly(HEMA) and a human melanoma cell line that constitutively produces both the 72- and 92-kDa gelatinases, we have found that alteration in cell shape, that is, a change in cell "roundness," resulted in a specific loss of the constitutive production of the 92-kDa gelatinase B. To examine this phenomenon further, cells were treated with an inhibitor of actin polymerization, cytochalasin D. This treatment also resulted in a loss of 92-kDa gelatinase B production, provided the cells were treated with drug from the out-set of the experiment. If the cells were allowed to attach and spread prior to drug exposure, no loss of 92-kDa gelatinase B production was observed. Similar to the poly (HEMA) results, cytochalasin D had little effect on production of the 72-kDa gelatinase A. Treatment with the tubulin polymerization inhibitor colchicine had no effect on 92-kDa gelatinase B production, nor did growth of the cells as three-dimensional tumor spheroids, although an alteration in cell morphology was observed in both instances. This phenomenon was studied in another system, namely, HL-60 cells, which were induced to differentiate into macrophage-like cells in response to TPA treatment and consequently produce the 92-kDa gelatinase B. HL-60 cells treated with TPA and cytochalasin D failed to produce the 92-kDa gelatinase B. These results suggest that the 92-kDa gelatinase B can be regulated by alterations in cell shape but more specifically, by alterations in the organization of the actin cytoskeleton. Furthermore, the mechanism responsible for cell shape/actin cytoskeletal down-regulation of the 92-kDa gelatinase B may be common to many cell types competent to produce this enzymatic activity. PMID- 7796887 TI - Retinoic acid-induced heparin binding protein (RIHB) binds to embryonal chondrocytes and cartilage primarily via proteoglycans. AB - Retinoic acid-induced heparin binding protein (RIHB) is a highly basic, secreted polypeptide expressed during early chick embryogenesis. We have characterized the binding of 125I-labeled RIHB to embryonal chondrocytes in culture. No saturable, high-affinity binding can be observed on these cells. Furthermore, no 125I labeled RIHB was internalized into the chondrocytes at 37 degrees C. The low affinity binding of 125I-labeled RIHB observed can be competed with another heparin binding factor, fibroblast growth factor 2, as efficiently as with unlabeled RIHB. The binding can also be almost completely inhibited by preincubation of the 125I-labeled RIHB with heparin or with a monoclonal antibody which recognizes the heparin binding site of both RIHB and HBNF. When cross linking experiments are performed with 125I-labeled RIHB, specific RIHB containing high-molecular-weight complexes are observed; however, these represent only a very small fraction of the bound material. Immunohistochemical analyses of embryonic wing cartilage demonstrate that a significant fraction of bound RIHB can be removed from unfixed tissue simply by rinsing with phosphate-buffered saline. The remaining RIHB can be removed partially by incubation with heparitinase I or III and completely when the incubation is performed with chondoitinase A, B, C. These results demonstrate that RIHB binds to embryonal chondrocytes and cartilage primarily through proteoglycans of both heparan sulfate and chondroitin sulfate types. PMID- 7796889 TI - Cell cycle-related changes in F-actin distribution are correlated with glycolytic activity. AB - XTH-2 cells, a cell line derived from tadpole heart endothelial cells, were blocked at the end of the G1 phase of the cell cycle using desoxyguanosine (dG). Stress fibers are the dominant actin fibril structure in blocked cells. They disappear starting with the release of the dG block until the G2 phase of the cell cycle. In addition, after the release peripheral lamellae and microspikes appear, indicating increased surface motility of the cells. Concomitantly with these changes, net lactic acid production is increased while oxygen consumption remains constant. Increase in the content of F-actin per cell takes place only in subconfluent cultures. Similar morphological changes (organization of F-actin) have been induced by phorbol myristate acetate treatment. These are also accompanied by an increase in lactic acid production and unaltered oxygen consumption. Therefore, the changes in energy metabolism are supposed to result from the rearrangement of the F-actin network: The emanating loose fibrillar pattern provides an increased surface for the association with glycolytic enzymes, which enhances enzyme activity and represents a more motile state. The increased energy demand of the more motile structures is supplied predominantly by ATP derived from glycolysis. PMID- 7796888 TI - Microtubule integrity is necessary for the epithelial barrier function of cultured thyroid cell monolayers. AB - Vectorial transport in the thyroid epithelium requires an efficient barrier against passive paracellular flux, a role which is principally performed by the tight junction (zonula occludens). There is increasing evidence that tight junction integrity is determined by integral and peripheral membrane proteins which interact with the cell cytoskeleton. Although the contribution of the actin cytoskeleton to tight junction physiology has been intensively studied, less is known about possible interactions with microtubules. In the present study we used electrophysiological and immunohistochemical approaches to investigate the contribution of microtubules to the paracellular barrier in cultured thyroid cell monolayers which displayed a high transepithelial electrical resistance (6000 9000 ohm.cm2). Colchicine (1 microM) caused a progressive fall in electrical resistance to < 10% of baseline after 6 h and depolarization of the transepithelial electrical potential difference consistent with a significant increase in paracellular permeability. The effect of colchicine on TER was not affected by agents which inhibit the major apical conductances of thyroid cells but was reversed upon removal of the drug. Immunofluorescent staining for tubulin combined with confocal laser scanning microscopy demonstrated that thyroid cells possessed a dense microtubule network extending throughout the cytoplasm which was destroyed by colchicine. Colchicine also produced changes in the localization of the tight junction-associated protein, ZO-1: its normally continuous junctional distribution was disrupted by striking discontinuities and the appearance of many fine strands which extended into the cytoplasm. A similar disruption in E-cadherin staining was also observed, but colchicine did not affect the distribution of vinculin associated with adherens junctions nor the integrity of the perijunctional actin ring. We conclude that microtubules are necessary for the functional and structural integrity of tight junctions in this electrically tight, transporting epithelium. PMID- 7796890 TI - Analysis of the plasminogen system on rat glomerular epithelial cells. AB - Rat glomerular epithelial cells were grown to confluency on semipermeable tissue culture inserts and the plasminogen system of these cells was analyzed using enzyme assays, Western analysis, zymography, and reverse transcriptase-PCR. The glomerular epithelial cells are capable of activating exogenous plasminogen to plasmin by endogenous plasminogen activators. The cells produce both tissue plasminogen activator and urokinase-plasminogen activator with urokinase being the prominent activator. Both activators are present primarily on the basolateral side of the cells with urokinase found primarily at the cell surface presumably bound to its receptor and tissue-plasminogen activator found primarily in the matrix secreted by the cells on the semipermeable insert. The cells also produce plasminogen activator inhibitor-1 and urokinase-plasminogen activator receptor. Inhibition of plasminogen activation occurred with plasminogen activator inhibitor-1, anti-catalytic anti-tissue-plasminogen activator antibody, epsilon aminocaproic acid, which inhibits the binding of plasminogen through its lysine binding sites, and amiloride, which specifically inhibits urokinase. PMID- 7796891 TI - Mechanisms of activation and suppression in rat Nb 2 lymphoma cells: a model for interactions between prolactin and the immune system. AB - Rat Nb 2 lymphoma cells have been widely used to bioassay human growth hormone and many species of prolactin. Because their morphologic characterization suggests a T-cell lineage, Nb 2 cells were examined for their response to the T cell mitogens concanavalin A, pokeweed mitogen, and phytohemagglutinin P. As expected, a dose-response to rat prolactin was observed; however, attempts to induce proliferation using the conventional T-cell mitogens failed at concentrations normally stimulatory for rat primary lymphocytes. Moreover, when Nb 2 cells were simultaneously incubated with lectin plus a suboptimal concentration of prolactin, a dose-dependent suppression of the stimulatory effects of prolactin was observed with phytohemagglutinin P and pokeweed mitogen, although not with concanavalin A. Culture medium of prolactin-stimulated Nb 2 cells also contained a factor which inhibited normal rat lymphocyte activation by concanavalin A. The factor did not block induction of the IL-2 receptor and proliferation of IL-2-dependent CTLL-2 cells could be restored by exogenous IL-2. Because Nb 2 cells evolved from a lactogen-dependent lymph node tumor, these results may have implications for further understanding the role of pituitary hormones, particularly prolactin, in the immune response to hormone-dependent tumor progression. PMID- 7796892 TI - The presence and role of transmembrane transforming growth factor-alpha in cultures of rat liver epithelial cells. AB - We assessed the presence and the role of membrane TGF-alpha in two rat liver epithelial cell lines, either parental or transfected with c-fos proto-oncogene. c-fos overexpressing cells had more TGF-alpha-like activity in their membranes. When TGF-alpha was removed by elastase or neutralized, the growth rates of both cell lines were markedly reduced, but to a higher extent for parental cells. If membrane TGF-alpha seemed to play a key contribution in normal cell growth, both cell lines were unable to react to the addition of soluble TGF-alpha, showing that these two forms of growth factors are not equivalent. PMID- 7796893 TI - Prohibitin antiproliferative activity and lack of heterozygosity in immortalized cell lines. AB - Experiments were performed to determine whether prohibitin, an evolutionarily conserved gene with antiproliferative activity, has a role in cellular immortalization. A cell proliferation assay was used to examine one human cell line from each of four established immortal complementation groups, termed A, B, C, and D, and a normal human diploid fibroblast line. Only normal and Group B cells were inhibited from traversing the cell cycle after introduction of wild type prohibitin transcript. All of the immortalized cells expressed elevated levels of prohibitin mRNA and protein. Prohibitin gene structural characterization using Southern and single-strand conformation polymorphism (SSCP) analyses distinguished two alleles. One is cleaved at a polymorphic intronic EcoRI site, exhibits an exon 6-associated SSCP, and is homozygous only in Group B cells. The other is not cleaved at the EcoRI site, has a different exon 6 SSCP pattern, and is homozygous in Groups A, C, and D. In contrast, normal cells are heterozygous for the alleles. These results suggest that prohibitin may play a role as a tumor suppressor in the immortalization of Group B cells. PMID- 7796894 TI - Apoptosis induced by IL-2 withdrawal is associated with an intracellular acidification. AB - It is known that phorbol esters can protect IL-2-dependent lymphocytes against apoptosis induced by IL-2 withdrawal. However, the mechanism of this effect remains unclear. In this article we show that apoptosis induced by IL-2 withdrawal in the CTLL-2 cell line correlates with a decrease in intracellular pH (pHi). Supplementing the incubation medium with phorbol esters during IL-2 deprivation protects CTLL-2 cells against both apoptosis and intracellular acidification. Interestingly, IL-4 also supports short-term cell survival and maintenance of normal pHi. The protein kinase inhibitor staurosporine prevents the protective effects of IL-2, PMA, and IL-4 on apoptosis and intracellular acidification. In contrast, inhibition of the Na+/H+ antiporter by 5-N-ethyl-N isopropyl amiloride reverts the protective effects of PMA and IL-4, but only weakly affects IL-2-mediated suppression of apoptosis. Taken together, these results indicate that intracellular acidification may be an important event during apoptosis induced by IL-2 deprivation in the CTLL-2 cell line. Moreover, they suggest a key role for protein kinase C activation both in the maintenance of pHi and in the suppression of apoptosis, through mechanisms which rely on the activation of the Na+/H+ antiporter to a different extent, depending on the rescuing factor employed. PMID- 7796895 TI - Accumulation of histone H1(0) during early Xenopus laevis development. AB - It is known that a transition in the linker-histone variants takes place within chromatin during early development of Xenopus laevis; a cleavage-type H1 is replaced by the somatic type. Based on cytofluorimetric analysis of the distribution of the embryo cells in the cell cycle, we showed that this previously described transition occurs when significant modifications of the proliferative capacities of the cells occur. Moreover, this analysis allowed us to show that cell proliferation decreases gradually after the gastrula stage of development. This period terminates with the arrest of more than 90% of cells in the G0/G1 phase of the cell cycle at stage 45. We showed that the major accumulation of the differentiation-specific H1 subtype, histone H1(0), occurs at this time. H1(0), first detected in a restricted set of tissues, is then widely expressed during the later development at stage 45. Moreover, the double staining of nuclei isolated from embryo cells, for H1(0) and DNA, allowed us to show that this accumulation of H1(0) is not restricted to arrested cells. The example of the Xenopus early development shows that there may be an adaptation of the type of H1 expressed to the proliferative abilities of cells. This observation may provide insight into the significance of the expression of different H1 subtypes during development. PMID- 7796896 TI - Factors hindering access to abortion services. AB - Although abortion services are readily available in large urban areas to those able to pay, a 1993 survey of U.S. abortion providers shows that access to service is still problematic for many women because of barriers related to distance, gestation limits, costs and harassment. Among women who have nonhospital abortions, an estimated 24% travel at least 50 miles from their home to the abortion facility. Although 98% of providers will perform abortions at eight weeks after the last menstrual period, only 48% will perform abortions at 13 weeks and 13% at 21 weeks. Half of nonhospital abortion providers estimate that more than four days elapse on average between their patients' first telephone contact and the date of the procedure; one in seven say that more than one week elapses. Most women are able to obtain abortion services in one visit to a clinic. The average woman having a first-trimester nonhospital abortion with local anesthesia paid $296 for the procedure in 1993, up from $251 in 1989. On average, nonhospital facilities charged $604 at 16 weeks of gestation and $1,067 at 20 weeks. Eighty-six percent of nonhospital facilities providing 400 or more abortions in 1992 were the targets of antiabortion harassment. Picketing at facilities and the homes of staff members, vandalism and chemical attacks increased significantly between 1988 and 1992, but the incidence of bomb threats decreased. PMID- 7796897 TI - The impact of an increase in family planning services on the teenage population of Philadelphia. AB - In an assessment conducted 30 months after a Philadelphia-area project increased the resources that community family planning agencies devoted to teenage services, teenagers in targeted communities showed no generalized improvement in rates of pregnancy and childbearing, in knowledge or use of clinic services, or in attitudes toward contraception compared with those of teenagers in the entire city. Samples of adolescents aged 14-18 from the clinics' catchment areas and from the entire city were interviewed in mid-1988, when the project's activities began, and 2.5 years later. The results suggest that while community family planning clinics may provide effective services to the teenagers who seek them out, they may not be the most effective strategy for decreasing rates of pregnancy and childbearing in the overall teenage population. PMID- 7796899 TI - Using induced abortion to measure contraceptive efficacy. AB - Data from a 1989-1990 case-control study of contraceptive efficacy in Norway compare contraceptive use among women who requested an abortion (1,386 cases) with women who responded to a general fertility survey (2,627 controls). In a logistic regression analysis measuring contraceptive efficacy as the odds of avoiding a pregnancy that terminated in an induced abortion compared with the odds for nonuse, consistent condom use was found to lower fecundity by 88.9%, diaphragm use by 89.3%, the pill by 97.8%, the IUD by 97.6%, vasectomy by 99.5%, and female sterilization by 99.8%. The relative contraceptive efficacy of the condom, the IUD and the pill did not vary by marital status or parity but did vary with age; the proportion by which each of these methods reduced fecundity declined among successively older age-groups. PMID- 7796898 TI - Are primary care residents adequately prepared to care for women of reproductive age? AB - A 1991 study of 115 internal medicine and 28 family practice residents at a large inner-city public hospital finds that both groups would perform poorly in providing preconception counseling to women of reproductive age. More than 40% of residents failed to indicate that they would provide a healthy woman with information on rubella immunization and family planning or counseling on sexually transmitted diseases and safer sex. When counseling a diabetic woman seeking pregnancy, 74% would not have discussed congenital anomalies with her and 45% would not have considered discontinuing oral hypoglycemics if she became pregnant. Furthermore, 58% would have neglected to review or change hypertension medications in a newly diagnosed pregnant woman. Although both internal medicine and family practice residents had positive attitudes toward offering preconception care, family practice residents had significantly higher attitude scores. No clear improvement was found in patient management, attitude or knowledge scores as residents progressed from their first to their third year of training. PMID- 7796900 TI - Combined use of condoms with other contraceptive methods among inner-city Baltimore women. AB - Data from a street survey conducted among 717 women aged 17-35 in two inner-city Baltimore communities in 1991-1992 indicate that 17% of the entire sample, 38% of women using the pill and 11% of users of methods other than the pill used a condom in addition to another method the last time they had intercourse. Although adolescents reported the highest rate of combined condom and pill use (22% of 17 19-year-olds), condom use was significantly associated with pill use among adult women (odds ratio of 1.57) but not among adolescents (odds ratio of 1.03). Condom use was negatively associated with use of methods such as the diaphragm, the IUD, the implant and the sponge (odds ratio of 0.21) among both adolescents and adults. Logistic regression analyses show that positive attitudes toward safer sex, ever having refused sex without a condom and believing in condom efficacy all significantly predicted use of the condom with another method. Having ever been tested for HIV was negatively related to combined use, while behavioral risk factors showed no association. PMID- 7796901 TI - High-risk sexual behavior at a midwestern university: a confirmatory survey. AB - According to a 1991 study of sexual behavior based on a random sample of heterosexual undergraduates at a Midwestern university, 80% of the males and 73% of the females had experienced vaginal or anal intercourse. The average age at first vaginal intercourse was 17.2 years for both sexes. Seventeen percent of the sexually experienced males and 18% of the sexually experienced females had engaged in heterosexual anal intercourse; among these respondents, the average age at first anal intercourse was 20.3 for males and 19.1 for females. Although less than four years, on average, had elapsed since the respondents had first had vaginal intercourse, males reported an average of 8.0 lifetime vaginal-sex partners and females reported an average of 6.1. Overall, the findings from this random sample of students are similar to those from a 1988 convenience sample of the same college population. PMID- 7796903 TI - Cyclin-dependent kinases and pRb: regulators of the proliferation-differentiation switch. AB - The retinoblastoma susceptibility gene (RB1) is essential for normal embryonic development. Loss of RB1 leads to uncontrolled proliferation of a number of cell types but may also prevent proper terminal differentiation. The growth suppressive and differentiation-inducing properties of pRb are impaired by cyclin dependent kinase (cdk)-mediated phosphorylation. Hence, inhibition of cdk activity is probably a prerequisite for terminal differentiation. Indeed, forced cyclin or cdk expression can prevent terminal differentiation in various cell types, probably through inhibition of pRb and, possibly, differentiation-specific transcription factors. PMID- 7796902 TI - State actions on reproductive health issues in 1994. PMID- 7796904 TI - The proton-pumping respiratory complex I of bacteria and mitochondria and its homologue in chloroplasts. AB - The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first of the respiratory complexes providing the proton motive force which is essential for the synthesis of ATP. Closely related forms of this complex exist in the mitochondria of eucaryotes and in the plasma membranes of purple bacteria. The minimal structural framework common to the mitochondrial and the bacterial complex is composed of 14 polypeptides with 1 FMN and 6-8 iron-sulfur clusters as prosthetic groups. The mitochondrial complex contains many accessory subunits for which no homologous counterparts exist in the bacterial complex. Genes for 11 of the 14 minimal subunits are also found in the plastidial DNA of plants and in the genome of cyanobacteria. However, genes encoding the 3 subunits of the NADH dehydrogenase part of complex I are apparently missing in these species. The possibility is discussed that chloroplasts and cyanobacteria contain a complex I equipped with a different electron input device. This complex may work as a NAD(P)H: or a ferredoxin:plastoquinone oxidoreductase participating in cyclic electron transport during photosynthesis. PMID- 7796905 TI - A kinetic model for comparing proteolytic processing activity and inhibitor resistance potential of mutant HIV-1 proteases. AB - A kinetic model is presented for the comparison of potential proteolytic processing activities of wild-type and mutant human immunodeficiency virus proteases in the presence and absence of protease inhibitors. The protease processing of gag substrate in the immature virions is assessed by the kinetic parameters, kcat, Km and Ki. The relationship of the estimated potential processing activities to the viability of the HIV mutants and their tendencies to resist inhibitors also are discussed. A fully developed model has the potential to stimulate the results of inhibitor resistance either in vivo or in cell culture. PMID- 7796906 TI - STE2/SCG1-dependent inhibition of STE4-induced growth arrest by mutant STE4 delta C6 in the yeast pheromone response pathway. AB - The yeast pheromone response pathway involves the activation of a heterotrimeric G protein composed by SCG1 (alpha) (also GPA1), STE4 (beta), and STE18 (gamma) subunits by the pheromone-activated receptors STE2 and STE3 in a and alpha cells, respectively. Upon exchange of bound GDP for GTP in the SCG1 subunit, the release of STE4/STE18 dimer occurs which, in turn causes activation of downstream effectors leading growth arrest and mating competence. Over-expression of STE4 also leads to growth arrest in a STE18 dependent manner. Removal of 6 amino acids from the C-terminus of STE4 rendered a subunit incapable of downstream signalling but still able to interact with STE18. This delta C6 mutant acts as a dominant negative because it blocks the growth arresting effect obtained by over expression of STE4. The inhibitory effect of STE4 delta C6 is dependent on the presence of the SCG1 subunit in a STE2 but not ste2 background. Inhibition of the growth arresting effect of STE4 by the delta C6 mutant is not due to competition at the effector site, but rather involves an intrinsic activity of STE2 that is dependent on SCG1. PMID- 7796907 TI - Cloning, functional expression and mRNA distribution of an inwardly rectifying potassium channel protein. AB - In GH3/B6 cells at least two different inward K+ currents are observed that are regulated by thyrotropin-releasing hormone and somatostatin, respectively. Using a polymerase chain reaction based approach a cDNA was isolated and functionally expressed in human embryonic kidney cells that encodes an inward rectifier K+ channel, rIRK3, with a predicted molecular mass of 49.7 kDa. Corresponding transcripts of 2.6 kb have been detected in rat brain, pituitary and GH3/B6 cells. In situ hybridization revealed that rIRK3 mRNA is distributed throughout the brain and occurs predominantly in the piriform cortex, indusium griseum, supraoptic nucleus, facial nucleus and cerebellar Purkinje cells. PMID- 7796908 TI - Identification of a mitochondrial form of kynurenine aminotransferase/glutamine transaminase K from rat brain. AB - A soluble aminotransferase with kynurenine aminotransferase (KAT) activity has been recently isolated from rat brain. This enzyme corresponds to a cytosolic form of glutamine transaminase K (GTK). In addition to the cytosolic enzyme, a mitochondrial-associated form of this KAT/GTK also exists. In the present work we have isolated a rat brain cDNA clone encoding a KAT/GTK enzyme identical to the soluble form but carrying an additional stretch of 32 amino acids at its NH2 terminus. Several structural features of this sequence resemble those of leader peptides for mitochondrial import. Evidence that the isolated cDNA encoded for mitochondrial KAT/GTK was obtained after transfection of HEK-293 cells with the cDNA coding for this new KAT/GTK isoenzyme. In fact, a significant enrichment of both KAT and GTK enzymatic activities was found in the crude mitochondrial fraction of the transfected cells. PMID- 7796909 TI - Cloning and expression of the cDNA coding for the erythrocyte isoenzyme of human acylphosphatase. AB - Three independent cDNAs coding for the erythrocyte isoform of human acylphosphatase were isolated and characterized. All the clones were incomplete at the 5' end, but Northern blot analysis using the cDNA as a probe showed the presence of an unusually long mRNA 5'-untranslated region. The transcript was present in a variety of human cell lines of different origins, although at different levels. Southern blot analysis on DNA from different individuals revealed a simple hybridization pattern. Large amounts of pure enzyme with kinetic characteristics very similar to those of the native protein were expressed in E. coli. PMID- 7796910 TI - Site specificity of p72syk protein tyrosine kinase: efficient phosphorylation of motifs recognized by Src homology 2 domains of the Src family. AB - Protein tyrosine kinase p72syk purified from rat spleen has been assayed for its ability to phosphorylate a number of peptide substrates derived from naturally occurring phospho-acceptor sites. The phosphorylation efficiency is extremely variable, depending on the peptide sequence, with Km values in the 3-1500 microM range. The by far best peptide substrates, with Km values of 3 and 4 microM are those reproducing the phospho-acceptor sites of Vav and HS1 proteins, respectively. These sites include multiple acidic residues flanking tyrosine on both sides and they also display the consensus sequences (YEDL and YEEV) preferred by the SH2 domains of the Src family. Alteration of this consensus in the HS1 peptide, by replacing either the glutamic acid or valine, also reduces the phosphorylation efficiency by p72syk. Also the replacement of acidic residues at position -1 and, to a lesser extent at positions -3 and -4 (but not at positions +3 and +5) are detrimental. These observations may suggest a role of p72syk in the recruitment of ligands/substrates for the Src family enzymes. We also show that the HS1 peptide can be used for the specific monitoring of p72syk since neither the two Src-related c-Fgr and Lyn kinases (needing a hydrophobic instead of acidic residue at position -1) nor CSK appreciably phosphorylate it. PMID- 7796911 TI - Complete separation of the beta,epsilon- and beta,beta-carotenoid biosynthetic pathways by a unique mutation of the lycopene cyclase in the green alga, Scenedesmus obliquus. AB - The mutant, C-2A'-34, lacks the beta, epsilon-carotenoids, alpha-carotene, lutein and loroxanthin. When grown under heterotrophic or mixotropic conditions this strain develops significantly higher levels of beta-carotene and violaxanthin than does the original developmental mutant of Scenedesmus, C-2A'. The decrease in chlorophyll a and chlorophyll b observed in C-2A'-34 is accompanied by the near absence of the LHC. The light intensity dependence of greening of this strain is comparable to that of C-2A'; the loss of the beta,epsilon-carotenoids and modification of the pool of beta,beta-carotenoids neither prevent the proximal pigment-protein complexes of photosystems I and II from developing nor cause any short term photosensitivity. The increase in the beta,beta-carotenoids in C-2A'-34 apparently compensates for the loss of the beta,epsilon-carotenoids required in formation of the proximal and distal antennae systems but not in the LHCs. PMID- 7796912 TI - Green-fluorescent protein mutants with altered fluorescence excitation spectra. AB - Using random mutagenesis and visual selection of fluorescent clones, we have isolated a T203I and a E222G mutant of the Aequorea green-fluorescent protein. Each mutant has one of the two fluorescence excitation bands of the wild type deleted and retains the other without a wavelength shift. This finding is consistent with each excitation band corresponding to a distinct spectroscopic state of the chromophore. Both mutations are single amino acid exchanges which in the linear sequence are located remotely from the chromophore but in the folded protein may be situated in its vicinity. We conclude that the mutations influence the fluorescence properties by changing the interactions between the chromophore and its protein environment. PMID- 7796913 TI - Unreliability of carotenoid electrochromism for the measure of electrical potential differences induced by ATP hydrolysis in bacterial chromatophores. AB - ATP hydrolysis induces the activation of the proton ATPase in chromatophores of Rhodobacter capsulatus supplemented with nigericine and 50 mM K+ (i.e. when delta pH < 0.2 units). The value of transmembrane electric potential (delta phi) driving this activation was measured using three different approaches: carotenoid electrochromism, uptake of SCN- and responses of the dye oxonol VI. The value of delta phi calculated from the SCN- uptake, on the basis of an internal volume determined experimentally, was about 140 mV, while that indicated by the electrochromic signal ranged between 35 and 70 mV. Only the value indicated by SCN- distribution is consistent with the energetic requirement for the activation of H(+)-ATPase. PMID- 7796914 TI - Effect of the Ca2+ channel activator CGP 28392 on reactivation of oxygen evolution of Ca(2+)-depleted photosystem II. AB - The effect of the Calcium channel activator, CGP 28392, on the reactivation of oxygen evolution in Ca(2+)-depleted Photosystem II (PS II) particles has been investigated. Ca(2+)-binding is associated with a functional water splitting complex of PS II. In the presence of the activator, a low affinity site of Ca(2+) binding is converted into a high affinity binding site. Following removal of the extrinsic proteins (17 and 23 kDa), any effect of the activator is no longer observed. Ca2+ channel inhibitors can inhibit the Ca(2+)-dependent reactivation of oxygen evolution. The activator partially protects against this type of inhibition. It is suggested that the extrinsic proteins form a Ca2+ channel-like structure at the donor side of PS II. PMID- 7796915 TI - A novel enzyme, maltose 1-epimerase from Lactobacillus brevis IFO 3345. AB - A novel enzyme, maltose 1-epimerase (MER), that catalyzes the interconversion of alpha and beta anomers of maltose was found in a cell-free extract of Lactobacillus brevis IFO 3345, and MER was purified to homogeneity from the crude extract. The M(r) of the enzyme was estimated to be 43,000 and 45,000 by HPLC gel filtration and SDS-PAGE, respectively. It showed optimum activity at pH 6.5-7.0. This novel enzyme catalyzed the conversion of beta-maltose more effectively than disaccharides such as alpha-lactose and beta-cellobiose, whereas the relative velocities for beta- and alpha-D-glucose were about one forth of that for beta maltose. PMID- 7796916 TI - Behavior of Rhizobium meliloti in oxygen gradients. AB - Rhizobium meliloti cells responded to an abrupt change in oxygen concentration by changing the cell speed (chemokinesis), but they did not alter the frequency at which swimming cells stopped briefly (aerotaxis). Changes in cell speed upon stimulation with oxygen coincided with changes in membrane potential. The cells did not form an aerotactic band in a spatial gradient of oxygen as do the cells of other bacterial species. The fixL and fixJ genes which encode a heme containing protein kinase that senses oxygen and a response regulator, respectively, were not involved in the behavior of R. meliloti in oxygen gradients. PMID- 7796918 TI - Apoptosis without decrease of cell DNA content. AB - Apoptosis of human B cells and murine T and B cells was analyzed by DNA agarose gel electrophoresis, clamped homogeneous electric field, measurement of cell DNA content by flow cytometry, transmission electron microscopy and by UV microscopy. Apoptosis was induced by etoposide (an inhibitor of topoisomerase II), by the calcium ionophore ionomycin or by cross-linking of membrane immunoglobulins (Ig) with anti-Ig-antibodies. Two types of apoptosis could be defined. Apoptosis resulting in small DNA fragments (180-200 base pairs and multiples thereof) was associated with a typical 'ladder' in agarose gel electrophoresis and a decrease in cell DNA content assessed by flow cytometry. Conversely apoptosis with large DNA fragments (100-150 kilobase pairs) was only demonstrated by clamped homogeneous electric field but was not associated with decreased cell DNA content or the observation of DNA ladders. Nuclear condensation without fragmentation was more frequent when apoptosis generated large DNA fragments. The type of apoptosis appears to be an intrinsic property of each cell type. PMID- 7796917 TI - Atomic structure at 2.5 A resolution of uridine phosphorylase from E. coli as refined in the monoclinic crystal lattice. AB - Uridine phosphorylase from E. coli (Upase) has been crystallized using vapor diffusion technique in a new monoclinic crystal form. The structure was determined by the molecular replacement method at 2.5 A resolution. The coordinates of the trigonal crystal form were used as a starting model and the refinement by the program XPLOR led to the R-factor of 18.6%. The amino acid fold of the protein was found to be the same as that in the trigonal crystals. The positions of flexible regions were refined. The conclusion about the involvement in the active site is in good agreement with the results of the biochemical experiments. PMID- 7796919 TI - Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit. AB - The ATP-sensitive K-channel plays a central role in insulin release from pancreatic beta-cells. We report here the cloning of the gene (KCNJ6) encoding a putative subunit of a human ATP-sensitive K-channel expressed in brain and beta cells, and characterisation of its exon-intron structure. Screening of a somatic cell mapping panel and fluorescent in situ hybridization place the gene on chromosome 21 (21q22.1-22.2). Analysis of single-stranded conformational polymorphisms revealed the presence of two silent polymorphisms (Pro-149: CCG-CCA and Asp-328: GAC-GAT) with similar frequencies in normal and non-insulin dependent diabetic patients. PMID- 7796920 TI - Peroxisomal-microsomal communication in unsaturated fatty acid metabolism. AB - The addition of 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to peroxisomes decreased the production of acid-soluble radioactivity formed by beta-oxidation of [1-(14)C]arachidonate due to substrate removal by esterification into the acceptor. This peroxisomal-associated acyl-CoA:1-acyl-GPC acyltransferase activity was due to microsomal contamination. The production of acid-soluble radioactivity from [1-(14)C]7,10,13,16-22:4, but not from [3-(14)C]7,10,13,16 22:4 was independent of 1-acyl-GPC, with and without microsomes. By comparing rates of peroxisomal beta-oxidation with those for microsomal acylation, it was shown that the preferred metabolic fate of arachidonate, when added directly to incubations, or generated via beta-oxidation, was esterification by microsomal 1 acyl-GPC acyltransferase, rather than continued peroxisomal beta-oxidation. PMID- 7796921 TI - Intracellular transport of inositol-containing sphingolipids in the yeast, Saccharomyces cerevisiae. AB - Organelles of the early protein secretion pathway (ER, Golgi) are involved in biosynthesis and intracellular migration of the yeast sphingolipids, inositolphosphorylceramide (IPC), mannosylinositolphosphorylceramide (MIPC), and mannosyldiinositolphosphorylceramide (M(IP)2C). Cycloheximide and nocodazole neither block biosynthesis of sphingolipids, nor ER to Golgi transport of IPC. In contrast, treatment of yeast cells with brefeldin A, which affects integrity of the Golgi, decreases formation of IPC and MIPC. Interruption of late steps of protein secretion (Golgi to plasma membrane transport) in temperature-sensitive secretory mutants prevents sphingolipids from being transported to the cell periphery. PMID- 7796922 TI - [ATP-sensitive potassium channel and hormone/neuropeptide]. AB - ATP-sensitive potassium channels (KATP) are the ion channels which are closely associated with cellular metabolism. A number of chemical compounds which block KATP facilitate the release of hormones or neuropeptides. For example, KATP blocking agents such as antidiabetic sulfonylureas and imidazolines stimulate insulin secretion from pancreatic beta-cells by decreasing KATP activity. On the other hand, so-called potassium channel openers, KATP-activating drugs which constitute a chemically diverse group of compounds, inhibit growth hormone secretion from anterior pituitary cells and release of gamma-aminobutylic acid from substantia nigra. Several endogenous substances also modulate release of hormone or neuropeptide by affecting KATP activity. Acetylcholine and histamine stimulate the release of endothelium-derived hyperpolarizing factor, which activates KATP in the plasma membrane of vascular smooth muscle cells. Both galanin and somatostatin inhibit insulin release from pancreatic beta-cells by opening KATP through the activation of G-protein. Glucagon-like peptide-1[7-36], which stimulates insulin secretion by indirectly blocking KATP in beta-cells, shows antidiabetic effects in patients with non-insulin-dependent diabetes mellitus. Endosulphine, an endogenous inhibitor of KATP, stimulates insulin secretion from pancreatic beta-cells. Accumulating knowledge of the modulation and function of KATP would help our understanding of the regulation and physiological role of hormones and neuropeptides. PMID- 7796923 TI - [The changes in natriuretic peptide receptors (NP-R) in the lung and kidney in DOCA-salt hypertensive rats]. AB - To elucidate the pathophysiological significance and the regulation of natriuretic peptide receptors (NP-R) in hypertension, we investigated the changes of NP-R in the lung, renal cortex and medulla using radioreceptor assay. We also examined the concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the atria and ventricles and plasma ANP concentration by specific radioimmunoassays. Elevated plasma ANP level, decreased atrial ANP concentration and increased ventricular ANP and BNP contents were observed in the DOCA-salt group when compared with the control group (p < 0.01). The ratio of BNP/ANP in the ventricle of the DOCA-salt rats was 50% of the control rats. The elevated plasma ANP secreted from the heart seems to reflect a defensive compensatory mechanism to counteract hypertension, and that ANP is the major natriuretic peptide secreted from the cardiac ventricle in DOCA-salt hypertensive rats. Scatchard plot analysis revealed that the maximal binding capacities (Bmax) of NP-R of the lung and renal cortex in DOCA-salt rats were significantly decreased from 71.0 +/- 10.4 to 38.4 +/- 5.9 (p < 0.05) and from 32.7 +/- 1.8 to 21.7 +/- 0.4 (fmol/mg. protein) (p < 0.01) compared with those in the control rats. The values of Bmax of the renal medulla between the two groups were not different. There was no significant change in the apparent dissociation constant (Kd) in the lung, renal cortex and medulla between the two groups. A competitive binding study using 125I- alpha-rANP1-28 and C-ANF4-23, a biologically silent clearance receptor (C-receptor) specific ligand, revealed that C-receptors are abundantly present in the renal cortex, while a relatively small quantity of C-receptor was detected in the renal medulla. In the lung, a substantial amount of C-receptor was detected. In the DOCA-salt treated rats, C receptors were decreased in the lung and renal cortex compared with the control rats. These results indicate that the down-regulation of NP-R, especially C receptor, was induced in the lung and renal cortex when plasma ANP levels were elevated in DOCA-salt hypertensive rats. In conclusion, our results suggest that down-regulation of C-receptor in the lung and kidney contributes to maintaining higher plasma ANP levels and maybe responsible for the counter-regulatory role of endogenous ANP in DOCA-salt rats. Our results show that the down-regulation of NP R in the lung was larger than that in the kidney, suggesting that the lung may play a dominant role in the regulation of the clearance of ANP through C receptors in vivo. PMID- 7796924 TI - [Microsatellite polymorphism of muscle glycogen synthase gene and non-insulin dependent diabetes mellitus]. AB - It has been reported recently that A2 allele of muscle glycogen synthase gene determined by Xba I RFLP (restriction fragment length polymorphism) is related to the frequency of NIDDM in Finland. Using PCR-RFLP analysis, we detected no A2 allele in Japanese patients with NIDDM and control. We found a new microsatellite of CA repeat in the human muscle glycogen synthase gene, and the polymorphism of the repeat number was detected by the polymerase chain reaction. Six different alleles were observed, indicating the highly polymorphic nature of this marker. We analyzed the repeat numbers and the genotypes in diabetics and control. The allele frequencies were not significantly different between NIDDM and control. However, the allele frequencies in the patients without high total cholesterolemia was significantly different from those of control. These findings suggest that the muscle glycogen synthase gene or neighboring genes are related to one of the disease genes of diabetes mellitus without high total cholesterolemia. PMID- 7796925 TI - [Testicular findings, endocrine features and therapeutic responses of men with idiopathic hypogonadotropic hypogonadism]. AB - The purpose of this study is to clarify the pathological and endocrinological variations of male idiopathic hypogonadotropic hypogonadism (IHH) from the viewpoint of testicular maturation. Twenty-five patients with IHH were classified into 3 groups according to the degree of germ cell maturation. The most mature germ cells in patients with severe IHH, moderate IHH and mild IHH were spermatogonia, primary spermatocytes and postmeiotic germ cells, respectively. All patients were treated with hCG alone or a combination of hMG-hCG for 1 year or more. The therapeutic efficacy of gonadotropin therapy was evaluated by findings of semen analysis, spermatogenesis and sexual maturation. The total GCI, which was expressed as the number of germ cells per Sertoli cell, diameter of the seminiferous tubules and testicular volume in mild IHH were the largest among the 3 IHH groups, and those in severe IHH were the smallest. Even in mild IHH, spermatogonial proliferation and meiotic activity were quantitatively smaller than those of normal pubertal boys. All patients showed extremely low basal testosterone levels. Response of serum testosterone to hCG administration correlated to the maturity of germ cells. Basal serum gonadotropin levels and responses to GnRH administration varied widely among the 3 groups. In particular, the response of serum gonadotropin to GnRH correlated to the maturity of the germ cells. Spermatogenesis could be initiated by hCG alone in IHH patients without cryptorchidism. Normal sperm density was obtained by hCG alone in the case of mild IHH; however, in moderate and severe IHH groups, hMG-hCG therapy was required for sufficient spermiogenesis. Sexual maturation was completely obtained by gonadotropin therapy within 1 year in moderate and mild IHH. However, in severe IHH, satisfactory sexual maturation could not be obtained within 1 year. The therapeutic prognosis for sexual maturation could be made based on the response to the hCG test at 6 months of gonadotropin therapy. In conclusion, the maturity of germ cells before treatment, which varies widely among patients with IHH, is a sensitive parameter for hypothalamo-pituitary-testicular function and the efficacy of gonadotropin therapy for testicular function. In severe IHH groups, to obtain satisfactory sexual maturation, the administration of testosterone should be considered in addition to gonadotropin replacement. PMID- 7796926 TI - [Effect of the GH-PRL superfamily on circulating plasma insulin-like growth factor-1]. AB - To elucidate the effects of growth hormone (GH), prolactin (PRL), and human placental lactogen (hPL) on the regulation of insulin-like growth factor (IGF-1), we compared plasma IGF-1 levels, the pattern of circulating IGF-1-IGF-binding protein complexes (IGF-1 complexes), and unsaturated binding protein (USBP) levels among 1) naturally growing Wistar rats at several developmental stages, 2) rats subcutaneously administered GH, and 3) hypophysectomized rats treated with each of the three hormones. We further evaluated the in vitro secretion of IGF-1 by primary cultured rat hepatocytes, following exposure to the hormones singly or in combination. Plasma IGF-1 and USBP levels were determined by radioimmunoassay and competitive radioassay, respectively. IGF-1 complexes were separated from plasma and culture medium by Sephadex G150 and HPLC gel-chromatography, respectively. The results were as follows. 1) In naturally growing rats, plasma IGF levels were low during fetal life and after birth until 28 days of age, and thereafter increased rapidly to reach an adult level by 35 days. At 35 days, the molecular distribution of IGF-1 switched from an infantile pattern (only 40Kd IGF 1 complex) to an adult form (IGF-1 complexes with both 40Kd and 150Kd proteins). In addition, 150Kd USBP became detectable after 28 days. 2) Administration of GH for 3 days to 13-day-old rats induced 150Kd USBP 9 days earlier than in controls, while plasma IGF-1 levels remained comparable throughout the period examined. 3) In the hypophysectomized rats, plasma IGF-1 levels decreased to approximately one fifth of those in untreated rats, accompanied by the disappearance of 150Kd USBP and 150Kd IGF-1 complex. However, when GH (but not PRL or hPL) was continuously administered for 72 hrs, plasma IGF-1 levels and the circulating profile of IGF-1 complexes were nearly restored to those in control rats. 4) Addition of GH (but not PRL) to the culture medium caused hepatocytes to secrete IGF-1, consisting of only the 40Kd IGF-1 complex. This effect was blocked by the simultaneous addition of hPL with GH. These findings indicate that, of the hormones analyzed, GH is the most important regulator of the plasma IGF-1 concentration and circulating complex forms during the developmental periods in rats, as is also thought to be the case in humans. PMID- 7796927 TI - [Phosphaturic effect of PTH during hypoxia and hypocapnia in rats]. AB - This study examined the effect of acute hypoxia or hypocapnia on renal phosphate excretion in thyroparathyroidectomized rats. Hypoxia is usually accompanied by a secondary hypocapnia due to hypoxic hyperventilation. Respiratory alkalosis has been described as blunting the phosphaturic effect of parathyroid hormone (PTH). In the present study, to know the effect of hypoxia on renal phosphate excretion in the absence of hypocapnia, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. The rats were divided into three groups depending on the arterial PO2 and PCO2 levels: 1) hypoxic normocapnic group; 2) normoxic normocapnic group; 3) normoxic hypocapnic group. Hypoxia was achieved by ventilating with 10% oxygen, and hypocapnia by hyperventilating with 25-30% oxygen. PTH infusion significantly increased fractional excretion of phosphate (FEPi) from 4.1 +/- 0.9 (mean +/- SE) to 37.7 +/- 2.6% in the hypoxic group (n = 7), from 1.4 +/- 0.3 to 27.4 +/- 2.5% in the normoxic group (n = 8), and from 1.5 +/- 0.4 to 19.5 +/- 1.2% in the hypocapnic group (n = 10). The change of FEPi (delta FEPi) after PTH infusion during hypoxia was significantly greater (33.6 +/ 2.1%) than that during normoxia (26.1 +/- 2.4%, p < 0.05). In contrast to this, hypocapnia blunted the phosphaturic response to PTH (18.0 +/- 1.1% delta FEPi, p < 0.05). Urinary adenosine 3', 5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion in all three groups. To test whether the enhanced phosphaturic effect of PTH during hypoxia and the blunted phosphaturic effect of PTH during hypocapnia are due to steps beyond the production of cAMP, cAMP was administered to the three groups. Cyclic AMP infusion displayed greater phosphaturia in the hypoxic group (n = 6, 30.0 +/- 1.4%) and less phosphaturia in the hypocapnic group (n = 7, 11.3 +/- 1.8%) as compared the the normoxic group (n = 6, 24.1 +/- 1.0%). In conclusion, acute hypoxia enhances the phosphaturic effect of PTH, whereas acute hypocapnia attenuates the phosphaturic effect of PTH. PMID- 7796928 TI - Adenosine 3',5'-cyclic monophosphate and the self-priming effect of gonadotrophin releasing hormone. AB - An in vitro perifusion system was used to ascertain the role of cAMP in the genesis of the self-priming effect of gonadotrophin-releasing hormone (GnRH) in rat pituitaries. Ten-minute pulses of 20 nmol/l GnRH administered 150 min apart resulted in the manifestation of the self-priming effect, an effect which was inhibited by 5 mumol/l cycloheximide. Forskolin (1 mumol/l) which does not stimulate luteinizing hormone (LH) secretion or affect the initial LH response to GnRH significantly potentiated the second response through protein synthesis dependent mechanisms. Additionally, an initial 10-min pulse of forskolin alone was sufficient to prime the pituitary to a subsequent pulse of GnRH 150 min later. Interestingly, similar amounts of LH were secreted in response to forskolin + GnRH or GnRH administered 150 min after forskolin. Flufenamate, an inhibitor of GnRH-stimulated increases in cAMP production prevented the manifestation of the self-priming effect of GnRH. Forskolin which bypasses the inhibitory effects of flufenamate on cAMP production reversed the flufenamate induced inhibition of the self-priming effect of GnRH through protein synthesis dependent processes. These results suggest that cAMP does not mediate the LH response to an initial exposure of GnRH, but does play a pivotal role in the genesis of the self-priming effect of GnRH through the stimulation of de novo protein synthesis. Once the newly synthesized proteins are available, the nucleotide is not required for the manifestation of the phenomenon. PMID- 7796929 TI - Growth hormone releasing factor and vasoactive intestinal peptide stimulate rat granulosa cell plasminogen activator activity in vitro during follicular development. AB - Growth hormone-releasing factor (GRF) and vasoactive intestinal peptide (VIP) are two structurally homologous peptides sharing common target cell receptor and known to enhance FSH-induced steroidogenesis of undifferentiated granulosa cell in vitro. Although VIP, has been reported to stimulate plasminogen activator (PA) activity in rat granulosa cells, our knowledge on the actions and interactions of these two peptides with FSH in the regulation of rat granulosa cell PA system during follicular development remains incomplete. Undifferentiated and differentiated rat granulosa cells from pre-antral (DES-treated rats) and antral (eCG-treated rats) follicles, respectively, were cultured in a chemically defined medium in the absence and presence of FSH (400 ng/ml), GRF (10(-8)-10(-5) M) and/or VIP (10(-9)-10(-5) M). Net secreted (PAs) and cell-associated (PAc) PA activities was measured by the fibrinolysis assay and characterized by the fibrin overlay method. Granulosa cell differentiative (progestin secretion) and proliferative (DNA synthesis) responses were analyzed by radioimmunoassay and [3H]thymidine incorporation, respectively. Both GRF and VIP stimulated PAs and PAc activities in a concentration-dependent manner in 24-h cultures of granulosa cells from the two stages of follicular development. They (10(-5) M) enhanced FSH stimulated PAs activity in granulosa cell cultures of pre-antral follicles, with GRF being more effective than VIP. On the contrary, only GRF (10 microM) potentiated FSH-induced PAs and PAc activities in cultures of granulosa cell from antral follicles. The stimulation of PA activity by these agonists decreased with the duration of culture irrespective of the stage of follicular development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796930 TI - The proximal milk protein binding factor binding site is required for the prolactin responsiveness of the sheep beta-lactoglobulin promoter in Chinese hamster ovary cells. AB - To identify cis-acting prolactin (PRL) response elements within the sheep beta lactoglobulin (BLG) promoter, CHO cells were co-transfected with a rabbit PRL receptor (PRL-R) expression plasmid and a number of BLG-CAT constructs. Resection through the 4200 bp BLG promoter diminished the PRL response. Mutation of the proximal binding site for milk protein binding factor (MPBF), a previously described mammary gland transcription factor, abolished the PRL inducibility of full length and shorter forms of the promoter. MPBF was shown to be similar to the Stat protein mammary gland factor (MGF) which has been shown to mediate PRL responsiveness of the rat beta-casein gene in mammary cells. MPBF binding activity was detected in the nucleus of CHO cells and was increased 2-6-fold in cells stably transfected with the PRL-R. The lactating mammary gland has high levels of MPBF binding activity and it is likely that this has an important role in the PRL induction of a variety of milk protein genes. PMID- 7796931 TI - Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy. AB - Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction. PMID- 7796932 TI - Mitogenic effects and nuclear localisation of procorticotrophin-releasing hormone expressed within stably transfected fibroblast cells (CHO-K1). AB - To investigate the intracellular localisation and biological activity of procorticotrophin-releasing hormone (proCRH), we have established stably transfected CHO-K1 cells expressing the rat pre-proCRH cDNA. Using immunoblot analysis of cell lysates of transfected CHO-K1 cells, we detected a major CRH immunoreactive band with an apparent molecular weight of approximately 19 kDa. This 19 kDa band could account for full length proCRH molecule which has not undergone post-translational modifications. Metabolic labelling followed by immunoprecipitation, SDS-PAGE and autoradiography indicated that no endoproteolytic processing of proCRH takes place within the transfected CHO-K1 cells. Immunofluorescence staining localises the CRH precursor to both the cytoplasm and to the nucleus in transfected CHO-K1 cells. This result was confirmed using subcellular fractionation techniques on radiolabelled CHO-K1 cells expressing immunoreactive CRH. A major CRH-immunoreactive band of 19 kDa was detected both in the microsomal and secreted fractions, indicating the presence of proCRH within the secretory pathway of these cells. This was also evident in the nuclear fraction, therefore confirming the nuclear localisation of proCRH. Analysis of DNA concentration, cell number and DNA synthesis showed that stably transfected CHO-K1 cells expressing proCRH have a higher proliferation and DNA synthesis rate than wildtype CHO-K1 cells or CHO-K1 cells transfected with pEE14 alone. Our results therefore suggest a mitogenic role for the intact proCRH molecule within CHO-K1 cells. Furthermore, treatment of mouse corticotrophic tumour cells (AtT20/D16-16) with conditioned medium from transfected CHO-K1 cells expressing proCRH, stimulated both DNA synthesis and cell proliferation above basal levels. Our results constitute the first reported direct evidence of a mitogenic role for proCRH acting on a corticotrophic cell population. PMID- 7796934 TI - Charge heterogeneity in wildtype and variant glucocorticoid receptors. AB - Two-dimensional electrophoresis was used to examine charge heterogeneity in glucocorticoid receptors (GCRs) from sublines of the thymic-derived, mouse P1798 lymphosarcoma which were sensitive (S) or resistant (R) to glucocorticoid mediated apoptosis. Previous work had identified the 97 kDa wildtype GCR (WT-GCR) in S cells and two variant GCRs in R cells: a 45 kDa, steroid-binding truncated GCR (TR-GCR), and a 97 kDa non steroid-binding GCR (NSB-GCR). Using denaturing isoelectric focusing, we now show that S cells as well as adult mouse thymus gland also express the NSB-GCR at pI 5.6 in addition to the WT-GCR which resolves between pH 5.9-7.1. Thus, the NSB-GCR is detected in steroid-sensitive cells and is not unique to R cells. Separation of receptors by native isoelectric focusing suggested that the TR-GCR in R cells resolved at a single, high pI (8.1) relative to the WT-GCR which resolved in a broad range (pI 5.8-8.0). The high pI of the TR GCR may alter its functional activity thereby contributing to the resistance phenotype. PMID- 7796936 TI - Hypothalamic GLUT 4 expression: a glucose- and insulin-sensing mechanism? AB - The insulin-regulatable glucose transporter, GLUT 4, is expressed primarily in peripheral tissues (skeletal muscle and adipose tissue). In response to insulin this transporter moves rapidly from an intracellular storage site to the plasma membrane, thus accounting for the substantial increase in glucose uptake by these tissues following insulin stimulation. The recent finding that GLUT 4 is also expressed in the hypothalamus suggests that this brain region, which is outside the blood-brain barrier and therefore sensitive to circulating insulin, may experience stimulation of glucose uptake in response to insulin. We propose that this may allow regions of the hypothalamus to respond directly to elevated blood glucose, constituting a form of metabolic regulation by allowing circulating glucose (and therefore insulin) in concert with other mechanisms to maintain blood glucose homeostasis. We consider the possible physiological role of such a mechanism and speculate that disturbances of this mechanism may occur in endocrine disease associated with insulin resistance. PMID- 7796935 TI - Modulation of thyroid hormone action by mutant thyroid hormone receptors, c-erbA alpha 2 and peroxisome proliferator-activated receptor: evidence for different mechanisms of inhibition. AB - Thyroid hormone action is not only determined by hormone availability, but also by target organ sensitivity. A dominant negative interaction is known to occur between thyroid hormone receptors (TRs) and the non-ligand binding splicing variant c-erbA alpha 2 as well as mutant TR beta 1 from kindreds with resistance to thyroid hormone. We compared the inhibitory effect of naturally occurring mutant hTR beta 1, artificially created hTR alpha 1 mutants, c-erbA alpha 2 and the human peroxisome proliferator-activated receptor (hPPAR) on three prototypic T3-response elements (TREs), TRE-PAL, DR + 4 and TRE-LAP. The inhibitory effect of mutant hTR alpha 1 and beta 1 occurred only on TRE-LAP and to a minor degree on DR + 4 when equimolar ratios of mutant/wildtype receptor were present. In contrast, the c-erbA alpha 2 splicing variant and the hPPAR inhibited TR action on all three TREs. Gel mobility shift experiments in the presence of T3 showed increased binding of mutant hTR alpha 1 and beta 1 only to TRE-LAP compared to the binding of wildtype hTRs, thereby explaining their TRE-selective dominant negative potency. Contrarily, equal amounts of c-erbA alpha 2 or hPPAR protein did not bind to either of the three response elements even in the presence of RXR. Since the TR:RXR heterodimers were only partially displaced from DNA in the presence of excess amounts of c-erbA alpha 2, it is likely that the TRE unspecific dominant negative action of c-erbA alpha 2 is due in part to competition for DNA-binding and for TR-auxiliary proteins. In contrast, equimolar amounts of hPPAR completely inhibited the DNA-binding of hTR beta 1:RXR heterodimers, but not of TR:TR homodimers, suggesting that hPPAR has a higher RXR binding affinity and is therefore a potent competitor for intranuclear RXR. Since thyroid hormones and peroxisome proliferators regulate in part a similar subset of target genes involved in fatty acid metabolism, these results suggest the possibility of cross-talk among the thyroid hormone and peroxisome proliferator signalling pathways. In summary, the results suggest that thyroid hormone action can be modulated by at least three different mechanisms: (i) increased binding of mutant hTRs to specific TREs; (ii) efficient competition for limiting amounts of RXR through the preferential formation of hPPAR:RXR, rather than TR:RXR heterodimers; and (iii) competition for binding to DNA and to auxiliary proteins other than RXR in the case of c-erbA alpha 2. PMID- 7796938 TI - Protein kinase C inhibition of in vitro FSH-induced differentiation in pig granulosa cells. AB - In granulosa cells, growth factor IGF I plays a major role in both growth and differentiation, acting through an autocrine/paracrine mechanism, and its production is regulated by FSH, via cyclic AMP (cAMP). As protein kinase C is also involved in granulosa cell function, we investigated the possibility that its activation could balance the positive effects of FSH. Using pig granulosa cells cultured in vitro, we studied the effects of protein kinase C activation by tetradecanoylphorbol acetate (TPA) on IGF I mRNA level. We also checked morphological modifications, cAMP production and steroidogenesis at the P450 side chain cleavage mRNA and progesterone levels. Our data demonstrate that protein kinase C activation antagonizes the in vitro FSH-induced differentiation, particularly morphological modifications and accumulation of IGF I mRNA. These inhibitory effects on FSH responses suggest that there could be a balance between protein kinase A and protein kinase C pathways in regulating differentiation in pig granulosa cells. PMID- 7796933 TI - Multiple intracellular signallings are involved in thyrotropin-releasing hormone (TRH)-induced c-fos and jun B mRNA levels in clonal prolactin cells. AB - In mammosomatotropes GH3B6 cells, one of the primary responses to thyrotropin releasing hormone (TRH) is the parallel induction of two proto-oncogenes, c-fos and jun B, which code for constituents of AP1 transcription factor. To better understand the mode of action of TRH and to look for possible functions of c-fos and jun B in these cells, we have investigated the role of different intracellular signals in the induction of each proto-oncogene on the one hand, and on prolactin (PRL) release and PRL gene expression on the other hand. Northern and dot-blot analyses revealed that the activation of protein kinase C (PKC)-, Ca(2+)- or adenylyl cyclase-dependent pathways acutely increased both c fos and jun B transcripts. However, a gene specific responsiveness was revealed using phorbol 12-myristate 13-acetate (TPA) and several combined treatments. The simultaneous activation of PKC and Ca(2+)-dependent pathways resulted in synergistic stimulations of c-fos mRNA levels only. Consistently, ionomycin plus low doses of TPA solely reproduced the potent effect of TRH on c-fos transcripts. Data collected from TRH and TPA down-regulated cells indicated that TRH probably recruits TPA-dependent PKC isoforms for stimulating c-fos but not jun B transcripts. On the contrary, the TRH-induced stimulation of either proto oncogene likely involves Ca(2+)-dependent mechanisms because calcium agonists and the peptide exert non-additive effects. Finally, the synergistic stimulations observed in response to TRH combined with forskolin, indicate that adenylyl cyclase-dependent mechanisms are interconnected with TRH-induced proto-oncogene expression. The overall study also reveals that among the agonists tested, the dihydropyridine Bay K 8644 and forskolin only were capable to induce a long lasting stimulation of c-fos and jun B mRNA levels, concomitant to increased levels of PRL transcripts, as does TRH. Considering that AP1 is assumed to be involved in signal transmission from the cell surface to the nucleus, it might be thus proposed that a common stimulation of c-fos and jun B gene expression is possibly involved in the activation of the PRL gene. On the other hand, the systematic coincidence between acute PRL release and proto-oncogenes expression suggest a role for c-fos and jun B in the control of genes involved in the secretory process. PMID- 7796937 TI - Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide stimulate two signaling pathways in CHO cells stably transfected with the selective type I PACAP receptor. AB - The properties of the pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor were studied on a clone of Chinese hamster ovary cells (CHO) stably transfected with the recombinant receptor. PACAP(1-27), PACAP(1-38) and VIP inhibited [125I-acetyl-His1]PACAP (1-27) binding, stimulated cyclic AMP and inositol phosphates production and induced [Ca2+]i increase with the same order of potency: PACAP(1-27) = PACAP(1-38) > VIP. The concentrations required for half maximal receptor occupancy, IP3- and [Ca2+]i increase were not different for both PACAPs (1 nM) and 100-fold higher than those required for cyclic AMP increase (0.010 nM). These data suggest that the occupancy of a portion of the total receptors available was sufficient for maximal cyclic AMP production but not for maximal IP3 production. It is concluded that the possibility of the type I PACAP receptor being coupled to a transduction pathway is not located at the level of the ligand but rather at the level of the G-proteins. PMID- 7796941 TI - Non-Target Effects of Live Vaccines. Langen, Germany, November 3-5, 1993. Proceedings of a workshop. PMID- 7796939 TI - Aging in rats is associated with an increase in adrenal apolipoprotein E. AB - Extrahepatic tissues including the adrenal cortex are capable of synthesizing apolipoprotein E (apoE). Locally synthesized apoE is believed to affect cellular uptake, transport and redistribution of cholesterol within that organ. We and another laboratory have previously reported that the adrenal cortex of aged rats has an elevated cholesteryl ester content. The aim of this work was to investigate whether this elevation is accompanied by increased adrenal apoE levels in aged rats. A Western blotting technique with polyclonal goat anti-human apoE antiserum was employed as a probe for studies. The results showed that: (a) anti-human-apoE antiserum not only detected apoE in human plasma and adrenal homogenate, but also cross-reacted with a protein (or proteins) resembling apoE in rat plasma and adrenal homogenate (or supernatant) with a molecular weight of 34,000-36,000; (b) rat adrenal apoE concentration (per unit weight of protein) increased with age; (c) the increase did not result from blood trapped in the gland, because after organ perfusion the adrenal of aged rats persistently exhibited 58% more apoE than that of young animals. In conclusion, rat adrenal apoE concentration appears to increase with age. Whether this increase mechanistically causes the accumulation of cholesteryl esters in the aged rat adrenal remains to be investigated. PMID- 7796940 TI - Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts. AB - The transforming growth factor beta (TGF-beta) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-beta 1 and beta 2 are potent inducers of steroid 5 alpha reductase (5 alpha R), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 x 10(5) cells) for 2 days in a serum free media and 5 alpha R activity was measured by the %-conversion of tracer [3H]-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5 alpha R activity in a dose related manner (control 3.0 +/- 0.4%, activin (1.2 x 10(-9) M) 6 +/- 0.7%, P < 0.01, (2.4 x 10(-9) M) 8.5 +/- 0.6%, P < 0.001). In comparison, androgen (DHT 10(-7) M) induction of 5 alpha R was 4.7 +/- 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 x 10(-9) M) and androgen (10(-7) M) did not result in additive or synergistic effect on 5 alpha R activity. In contrast, exposure of cells to an androgen (10( 7) M) and TGF-beta (2 x 10(-10) M) led to synergistic effects on 5 alpha R activity (control 1.5 +/- 0.1%, DHT 2.6 +/- 0.2% TGF-beta 1 4.8 +/- 0.5, TGF-beta 1 + DHT 9.2 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796943 TI - An historical outline of the development of live poliovaccine and its non-target effects. PMID- 7796942 TI - Viral vaccines in historical perspective. PMID- 7796944 TI - Recombinant polioviruses as candidate strains of oral poliovaccines. PMID- 7796945 TI - Manipulation of the cellular binding properties of poliovirus: implications for non-target effects of recombinant vaccines. PMID- 7796946 TI - Safety aspects of oral poliovirus vaccine campaigns. PMID- 7796947 TI - Tropism and immunoprotection in transmissible gastroenteritis coronaviruses. PMID- 7796952 TI - Capripoxvirus-based multivaccines. PMID- 7796951 TI - First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen. AB - In the absence of a truly representative animal model, the question of whether EBV-related diseases can be prevented by a vaccine has been studied for the first time in humans. A live recombinant virus based on the licensed vaccinia strain Tien Tan, expressing under the 11K vaccinia promoter the major EBV membrane antigen BNLF-1 MA (gp 220-340), was constructed and tested in three different human populations: EBV-positive and vaccinia-virus-exposed adults; EBV-positive, non-vaccinia-virus-exposed juveniles; and EBV and vaccinia virus-naive infants. No significant titre variations for EBV were observed in the adults, but EBV neutralising titres increased in the vaccinated juveniles, while antibodies to VCA of EBV remained unchanged. All nine vaccinated infants developed antibodies to MA (membrane antigen) with neutralising properties in vitro; three of these infants were infected by EBV via natural routes over a period of 16 months after vaccination and all ten unvaccinated control infants became infected. It has been shown for the first time that protection against and/or delay of EBV infection by the natural route is possible in humans and that live vaccinia vectors can be used and are efficacious. PMID- 7796949 TI - Highly attenuated poxvirus vectors: NYVAC, ALVAC and TROVAC. AB - Three highly attenuated and efficacious poxvirus-based vectors, NYVAC, ALVAC and TROVAC, are available for targeted applications as recombinant vaccines in both human and veterinary medicine. The attenuated phenotype of the three vectors is consistent with safe use for vaccination purposes, for the vaccinee, for unvaccinated contacts, and for introduction into the environment. The precise deletion of virulence and host range genes in the NYVAC vector precludes reversion to the virulent phenotype by back mutation. Dissemination of recombinant vaccines based on the NYVAC, ALVAC and TROVAC vectors is highly diminished, because of the genetic engineering in NYVAC and the natural attenuated phenotype of ALVAC and TROVAC. Studies have demonstrated that these recombinant vectors are genetically and phenotypically stable after serial passage in vitro as well as in vivo. NYVAC, ALVAC and TROVAC vectors are the only three poxvirus-based vectors that are classified as BSL1 agents. PMID- 7796948 TI - Adenovirus as vector for HIV: efficacy and safety issues. PMID- 7796953 TI - Target and non-target effects of a recombinant vaccinia-rabies virus developed for fox vaccination against rabies. PMID- 7796955 TI - Vaccinia virus recombinant vaccines for rinderpest. PMID- 7796954 TI - Novel vaccinia vector derived from the host range restricted and highly attenuated MVA strain of vaccinia virus. PMID- 7796950 TI - The safety and use of canarypox vectored vaccines. AB - ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds. PMID- 7796957 TI - Live bacterial vaccines for animals. PMID- 7796958 TI - Efficacy and safety of live recombinant BCG vaccines. AB - BCG has a long history of safe use in humans and is one of the best adjuvants known. The use of newer production methods may further reduce the risk of adverse side-effects. Early results with experimental animals have shown BCG to be an effective live recombinant delivery vehicle for several foreign vaccine antigens. Additional refinements to the safety and efficacy of the recombinant BCG vaccine vehicle are under development. PMID- 7796956 TI - The history of live bacterial vaccines. AB - Recent developments have made it possible to construct non-reverting live bacterial vaccine candidates with defined deletions of two or more genes. Such vaccines have proven safe and immunogenic in human volunteers. Since the virulent parent strains are only pathogenic to man (S. typhi, S. flexneri, and V. cholerae), they pose no threat to the environment. Besides holding promise as efficacious vaccines for protection against typhoid fever, bacillary dysentery and cholera, the attenuated strains are well suited as vectors for delivery of heterologous antigenic epitopes from micro-organisms such as Helicobacter pylori, Neisseira gonorrhoeae, rotavirus, HIV and many others. Instead of using a virulent parent bacterium as the starting organism for making a vector, attempts have recently been made to employ non-pathogenic bacteria of the normal human flora, such as Streptococcus gordonii for delivery of foreign antigens. At present, the feasibility of this approach for human beings remains to be proven. PMID- 7796960 TI - Vibrio cholerae CVD103-HgR live oral attenuated vaccine: construction, safety, immunogenicity, excretion and non-target effects. AB - In many controlled studies, CVD103-HgR has been shown to be safe and immunogenic and to offer a significant degree of protection against experimental cholera after a single dose. Its minimal excretion and limited ability to compete and survive in various ecosystems indicate that this strain presents little risk to the environment. Furthermore, the potential of CVD103-HgR to regain virulence by acquisition of the CT A or LT A gene is extremely remote even under optimal conditions. Therefore, CVD103-HgR possesses those traits desired in a live oral attenuated vaccine produced by recombinant DNA technology. PMID- 7796961 TI - Salmonellae as oral vaccine carriers. PMID- 7796962 TI - OmpA fusion proteins for presentation of foreign antigens on the bacterial outer membrane. AB - The ompA genes of Escherichia coli and Shigella dysenteriae have been used to construct a group of enterobacterial surface expression vectors for foreign genes. Linker oligonucleotides were inserted into the sequence corresponding to the third or fourth outer domain to allow in-frame sandwich fusion of foreign genes or epitopes into ompA. Influenza haemagglutinin was inserted without its leader peptide and anchor sequences and shown to be transferred as an ompA fusion protein to the bacterial surface in large amounts. The stability of this system depends on the stem structure (i.e. the bottom part) of the haemagglutinin unit which apparently initiates the folding process that extends into the ompA segment. This fusion construct can be used as a vector system and has been used to transfer to the bacterial surface several other proteins inserted into it, including beta-galactosidase, foot-and-mouth disease virus (FMDV) and malaria antigens. All are exported from the cytoplasm across both the inner and outer membranes to become exposed on the bacterial surface. Very hydrophobic segments or inserts with distinct secondary structures, such as the capsid protein, VP1 of FMDV, will, however, block this process. PMID- 7796959 TI - An overview of vaccine vectors. PMID- 7796963 TI - Aromatic vitamin-dependent Salmonellae as vaccines in food animals: efficacy and persistence. PMID- 7796964 TI - Safety and efficacy of modified live feline Toxoplasma gondii vaccine. PMID- 7796966 TI - Live virus vaccines for use in animals. PMID- 7796965 TI - Non-target effects of live vaccines: myth, reality and demagoguery. PMID- 7796967 TI - Rabies virus vaccines. AB - Many years of research and observations on bait uptake, efficacy, behavioural studies of foxes, reduction and elimination of rabies, population dynamics of foxes following oral vaccination, as well as annual exchanges of researchers' experiences, formed the scientific background for field trials extending over many years. These are the most extensive field studies for the testing of a rabies vaccine so far. The use of the techniques and strategies of oral immunisation of foxes against rabies using SAD B19 can eliminate wildlife rabies among foxes and raccoon dogs, as European experience has shown. The disease then also disappears completely in domestic animals and man. PMID- 7796969 TI - Target and non-target effects of retrovirus vectors used for gene therapy and vaccination. PMID- 7796968 TI - Potential hazards associated with influenza virus vaccines. AB - There is general agreement that human reassortant vaccine strains should be used only for the preparation of the viral glycoproteins (split vaccine), and not in toto after UV-inactivation. Live vaccines with lowered pathogenicity obtained by reassortment between human and avian strains may carry a risk of causing epizootics in other species, even though they are useful for the host for which they were designed. It has been argued that this dangerous situation is avoided when both parent strains are of human origin. For this reason, cold-adapted human master strains are used for reassortment with the most recent isolates from cases of human influenza. There is, however, convincing evidence that a reassortant between two human strains has caused severe epizootics among camels, which were not regarded as natural hosts for influenza A viruses. This sudden appearance of a reassortant camel virus had a precedent in experiments in which, starting from parent strains that are non-pathogenic for mice, highly pathogenic reassortants for this species were created. Safety requirements for cold-adapted reassortants must therefore take account of the fact that these new strains may have a high pathenogenicity for other species. PMID- 7796971 TI - New developments in the construction of safer and more versatile pseudorabies virus vaccines. PMID- 7796970 TI - Safety aspects in the development of an infectious bovine rhinotracheitis marker vaccine. AB - Clinical trials in cattle demonstrated that the IBR marker modified live vaccine based on the gE-deleted IBR strain Difivac is immunogenic and safe for bovines of all ages. Potential effects of the vaccine virus have also been tested in swine and sheep and proved safe for these species as well. For evaluation of other environmental aspects, the spread of the vaccine virus after immunisation was investigated. The data indicated that the vaccine virus may be shed by immunised animals but that it has a limited ability to pass from animal to animal. It was also demonstrated that the attenuated Difivac strain does not revert to virulence during calf passage. Preliminary results indicated that the gE-deleted vaccine virus of the IBR marker vaccine cannot be reactivated after dexamethasone treatment, an important advantage for a vaccine strain. Furthermore, immunisation with the Difivac strain reduced the ability of a superinfecting challenge virus to become latent or to be reactivated. PMID- 7796972 TI - Characterization of live pseudorabies virus vaccines. PMID- 7796973 TI - The influence of recombination on the genetic stability of pseudorabies vaccine virus. PMID- 7796974 TI - Effects of physiological state on oral habituation in developing rats: cellular and extracellular dehydration. AB - Hydrational state has been demonstrated to influence intake of various solutions in young rat pups. For instance, both cellular and extracellular dehydration produce an enhancement of intake in pups tested at 6 days of age. However, the behavioral mechanisms that result in increased intake following manipulations of hydrational state have been less extensively studied. The impact of hydrational state on behavioral responsiveness in young rat pups was examined by assessing the pattern of responding to a series of repeated oral infusions of diet. Pups were tested at 6, 12, or 18 days of age following either acute cellular dehydration produced by injection of 1 M NaCl or acute extracellular dehydration produced by injection of 10% polyethylene glycol (PEG). Oral responsiveness to a series of 30 brief infusions of one of four taste solutions (water, 10% sucrose, 0.135 M NaCl, or 1 M NaCl) was measured. Each infusion lasted 3 s and there was 1 min between infusions. The pattern of oral responding to solutions was affected by the developmental age of the pup, the hydrational state of the pup, and the solution offered, with the largest effects of dehydration observed in the youngest animals. In all conditions except one, pups habituated to repeated infusions. The exception was the failure of extracellularly dehydrated 6-day-old pups to display habituation to oral infusions of sucrose. These results suggest that, although intake is enhanced by both cellular and extracellular dehydration in very young pups, the behavioral changes responsible for the enhancement of intake after cellular dehydration are different from the behavioral changes resulting from extracellular dehydration. This dissociation of behavioral effects of dehydration in young pups demonstrates that intake measures alone may obscure subtle differences in behavior and argues for the utility of dissection of behavioral components in understanding the neural and physiological control of behavior. PMID- 7796975 TI - Systematic changes in gaping during the ontogeny of pecking in ring doves (Streptopelia risoria). AB - Food pecking in the ring dove is a skilled prehensile response that is similar to, but simpler than, many other prehensile responses. Previous work has shown that this response is initially poorly executed and requires experience for its accurate direction and coordination. The response involves two components: the thrusting of the bird's head toward food, and the opening and closure of the beak around food. Here, this second component, called gape, is followed through development with a precise measurement system. Four squabs moved through a similar sequence of three gape topographies, each of which is more efficient in picking up seed, during development. The present outcome, together with other work, argues for a substantial contribution of experience with pecking to the development of food pecking. We discuss the implications of these findings for understanding the ontogeny of motor control and for understanding how experience affects behavioral development. PMID- 7796976 TI - Effects of rearing condition on activity-induced weight loss. AB - This study evaluated the effects of differential rearing conditions on a rat protocol for various human syndromes. Subjects were 26 male Sprague-Dawley rats, 24 days old at the start of the experiment, matched according to weight, and randomly assigned to an isolation- or group-reared (4 rats/cage) condition. At 60 days of age (273 +/- 13 g), subjects were individually housed in cages allowing access to running wheels. Weight loss was produced through voluntary exercise and restricted food access. Animals in the isolation-reared condition lost weight at a faster rate and had heavier relative thymus weights than those in the group reared condition. Animals in both conditions ran equivalent distances and ate equivalent amounts of food. The data show that postweaning rearing conditions impact the interpretation of behavioral and physiological outcomes of animal models. The results implicate a shift from maternal regulation of pup physiological and behavioral systems to the broader social niche. PMID- 7796977 TI - Molecular cloning of a group of mouse pancreatic islet beta-cell-related genes by random cDNA sequencing. AB - To understand the molecular basis of glucose concentration-responsive insulin synthesis and secretion from pancreatic islet beta cells, a group of pancreatic islet beta-cell-related cDNAs was cloned. A pair of cDNA libraries was constructed from a mouse pancreatic islet beta-cell line of MIN6, which was cultured in either high glucose or low glucose media. By applying a random cDNA sequencing approach, 503 and 395 independent species were obtained from a total of 1,011 and 762 clones in the high glucose and low glucose library, respectively. The unknown genes comprised the majority of about 70% independent clones in both libraries. In Northern blot analysis, 311 (69.4%) of 448 independent clones showed positive signals within 72 h of autoradiographic exposure. Surprisingly, 150 (48.2%) out of 311 positive clones showed positive signals to MIN6 cells, but not to NIH/3T3 fibroblasts. The expression level of three unknown clones were glucose-concentration dependent. Combination of a random cDNA sequencing approach and Northern blot analysis is useful to obtain a large number of novel genes and islet beta-cell-related genes. PMID- 7796979 TI - Non-parallelism of islet amyloid polypeptide (amylin) and insulin gene expression in rats islets following dexamethasone treatment. AB - Islet amyloid polypeptide (IAPP), a novel islet hormone candidate, has been reported to be over-expressed relative to insulin in rats following dexamethasone treatment. In order to investigate the expression of IAPP and insulin following dexamethasone treatment of rats for 12 days, we applied in situ hybridization and immunocytochemistry, allowing us to evaluate islet changes in gene expression and morphology. Tissue concentrations of IAPP and insulin were measured by radioimmunoassay. A low dose of dexamethasone (0.2 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 249 +/- 13% and 150 +/- 24% of controls, respectively (p < 0.001 and p < 0.01). A high dose of dexamethasone (2.0 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 490 +/- 13% and 203 +/- 9% of controls, respectively (p < 0.001 and p < 0.001). The pancreatic concentration of IAPP increased more than that of insulin (p < 0.05). Morphometric analysis revealed that dexamethasone treatment induced both hyperplasia and hypertrophy of insulin cells. Changes in the cellular localization of IAPP and insulin mRNA were not observed. Thus, we conclude that the increased level of IAPP mRNA is due to both an increase at the cellular level as well as hyperplasia/hypertrophy of insulin cells. In contrast, the increased level of insulin mRNA appears to be due to hyperplasia/hypertrophy of insulin cells, since insulin gene expression decreased at the cellular level (p < 0.001 vs controls). These observations provide further evidence that IAPP and insulin gene expression are regulated in a non-parallel fashion, which may be relevant to the pathogenesis of non-insulin-dependent diabetes mellitus. PMID- 7796980 TI - Vanadate treatment rapidly improves glucose transport and activates 6 phosphofructo-1-kinase in diabetic rat intestine. AB - The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/l fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo 1-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,K-ATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. Km was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-1-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6 bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-1-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-1-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-1-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-1-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy. PMID- 7796978 TI - The relative roles of advanced glycation, oxidation and aldose reductase inhibition in the development of experimental diabetic nephropathy in the Sprague Dawley rat. AB - Advanced glycation is an important pathogenic mechanism in the development of diabetic complications. However, other biochemical processes, such as the polyol pathway or lipid and protein oxidation which can interact with advanced glycation can also yield tissue fluorescence and may also be implicated in the genesis of diabetic microangiopathy. Aminoguanidine is an inhibitor of advanced glycation, but it is not known if all of its effects are mediated by this mechanism. The present study explores the relative contributions of aldose reductase, oxidative stress and advanced glycation on the development of aortic and renal fluorescence and urinary albumin excretion in streptozotocin diabetic rats. The study groups included non-diabetic (control), streptozotocin diabetic rats and diabetic rats receiving aminoguanidine, the anti-oxidants butylated hydroxytoluene and probucol and the aldose reductase inhibitor, ponalrestat. Serial measurements of glycaemic control and urinary albumin excretion were performed every 8 weeks. At 32 weeks, animals were killed, tissues removed and collagen extracted for measurement of fluorescence. Diabetic rats had increased fluorescence in aorta, glomeruli and renal tubules. Aminoguanidine prevented an increase in fluorescence at all three sites suggesting that diabetes-related tissue fluorescence is predominantly due to advanced glycation. Ponalrestat retarded fluorescence in aorta only and butylated hydroxytoluene attenuated fluorescence at the renal sites but not in the aorta. Diabetic rats had increased renal cortical sorbitol levels. Ponalrestat normalized renal cortical sorbitol levels but aminoguanidine did not affect this parameter. The only agent to decrease plasma thiobarbituric acid reactive substances was butylated hydroxytoluene. Diabetic rats developed albuminuria over the 32-week period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796981 TI - Capillary surface area is reduced and tissue thickness from capillaries to myocytes is increased in the left ventricle of streptozotocin-diabetic rats. AB - The left ventricles of normal and diabetic rats, fixed by vascular perfusion were examined using modern stereological techniques to quantify changes in the morphology accompanying streptozotocin-induced diabetes. The heart weight to body weight ratio increased in diabetic rats whilst left ventricular volume remained unchanged. Papillary muscles from the diabetic animals showed prolonged time to peak tension and relaxation, and altered sensitivity to adrenalin and calcium. The apparent cardiomyopathy observed when body weight loss exceeds heart weight loss in experimental diabetes was accompanied by specific pathological changes in the composition of the left ventricle. In the diabetic animals the volume of extracellular components increased threefold and the volume of capillaries fell. The surface density and total surface area of capillaries was reduced, and oxygen diffusion distance to myocyte mitochondria increased. The volume fraction of myocyte mitochondria was reduced during streptozotocin-induced diabetes. PMID- 7796982 TI - Expression of insulin receptor on clonal pancreatic alpha cells and its possible role for insulin-stimulated negative regulation of glucagon secretion. AB - In pancreatic alpha cells, the existence and function of the insulin receptor has not yet been fully established. In this study, to confirm the expression of functional insulin receptors in pancreatic alpha cells, we performed: 1) insulin receptor binding assay, 2) Northern blot analysis and RT-PCR (reverse transcription-polymerase chain reaction) amplification of insulin receptor mRNA, 3) immunocytochemical staining, 4) biosynthetic labelling of insulin receptor protein using [35S]methionine, 5) analysis of insulin-stimulated autophosphorylation of the insulin receptor in glucagon secreting cell lines, In R1-G9 and alpha TC clone 6 cells. Glucagon secretion decreased with the addition of insulin in both cells. The receptor binding studies using [125I-Tyr-A14] insulin revealed that both cells possessed a significant number of insulin receptors (In-R1-G9:K1 = 2.1 x 10(9) mol/l-1, K2 = 6.2 x 10(7) mol/l-1, R1 = 0.27 x 10(4), R2 = 1.86 x 10(4) sites/cell; alpha TC clone 6: K1 = 2.1 x 10(9) mol/l 1, K2 = 7.3 x 10(7) mol/l-1, R1 = 0.27 x 10(4), R2 = 1.95 x 10(4) sites/cell). Northern blot analysis as well as RT-PCR amplification showed the mRNA specific for insulin receptor in both cells. By immunocytochemical staining using anti insulin receptor alpha-subunit antibody, positive immunostaining for insulin receptor was observed in both cells. [35S]Methionine labelling of both cells followed by immunoprecipitation using anti-insulin receptor antibody showed the correct size of the insulin receptor protein. The insulin receptor expressed in these cells underwent autophosphorylation by insulin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796984 TI - Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study. AB - We present the methodology for 45 degrees retinal photography and detail the development, application and validation of a new system of 45 degrees field grading standards for the assessment of diabetic retinopathy. The systems were developed for the EURODIAB IDDM Complications Study, part of a European Community funded Concerted Action Programme into the epidemiology and prevention of diabetes (EURODIAB). Assessment of diabetic retinopathy was carried out centrally by a trained reader of colour retinal photographs using the newly-developed system. The system proved to be acceptably accurate, repeatable repeatable and relatively simple to apply. It compared well with the recognised 'gold standard' 7-field 30 degrees stereo photography (assessed using a modified Airlie House classification scheme), against which the new system was validated in a series of 48 eyes. Selection was as a stratified random sample based on clinical retinopathy status: 5, no retinopathy; 25, non-proliferative retinopathy; 16, proliferative or photocoagulated; plus 2, eyes with potentially confounding lesions (vein occlusion). Simple presence of retinal lesions was correctly detected by both systems in 43 of the 48 eyes, giving 100% agreement on detection. Both systems correctly identified the two known cases of confounding vein occlusion. In eyes with diabetic retinopathy (n = 41), when severity was expressed in three groups: mild background, moderate/severe background and proliferative/photocoagulated, at least one grader (out of five) using the new system matched the verified results in 38 out of 31 (93%) eyes and three or more graders matched in 31 (76%) eyes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796983 TI - Effect of high glucose on formation of extracellular matrix components by cultured rat heart endothelial cells. AB - In an attempt to define the basis for the microvascular changes observed in diabetic myocardium, a study was undertaken on the effect of elevated glucose on the synthesis by rat heart endothelial cells of the extracellular matrix components, types VI, IV and I collagen, as well as fibronectin. Confluent cultures of these cells, isolated by fluorescence-activated cell sorting after treatment with rhodamine-labelled acetylated low density lipoprotein, showed a three to fivefold enhancement in the synthesis of type VI collagen after exposure for 48 h to high glucose (20 to 30 mmol/l), as determined by immunoblot analysis. Increased production of type IV collagen and fibronectin was also observed, but the change was smaller and no effect on type I collagen was found. Measurement of mRNA levels by hybridization with cDNA probes indicated that 48-h exposure to high glucose significantly increased the level of transcripts for type VI and IV collagens but not for type I collagen. While glucose consumption by endothelial cells in high glucose doubled in the initial 24-h period, utilization returned to normal by 48 h, concomitant with a reduction in GLUT1 transcript levels, suggesting that signals for stimulation of collagen synthesis must be active during the initial period of exposure to elevated glucose levels. PMID- 7796985 TI - Peptide-based radioimmunoassay for the two isoforms of the human insulin receptor. AB - The insulin receptor exists in two isoforms differing by the absence (HIR-A) or presence (HIR-B) of 12 amino acids in the COOH-terminus of the alpha-subunit as a consequence of alternative splicing of exon 11. In this study, we developed a radioimmunoassay for the two isoforms employing antibodies raised against two peptides, one (Pep-12) corresponding to residues encoded by exon 11, and the other (Pep-13) corresponding to a COOH-terminal domain of the alpha-subunit which is common to both HIR-A and HIR-B isoforms. These peptides were iodinated and used as both ligands and standards. The assay is specific, highly reproducible, and sensitive with a detection limit of 10 fmol of receptor. One mole of purified insulin receptor, measured by Scatchard analysis, is read as one mole of receptor in the radioimmunoassay with either Pep-12 or Pep-13 as standards. The radioimmunoassay is applicable to the measurement of total content and relative abundance of the two isoforms in extracts from various tissues. We applied the radioimmunoassay to measure the relative abundance of the two isoforms in fat and muscle from normal, obese non-diabetic and non-insulin-dependent diabetic (NIDDM) subjects. Results demonstrate that expression of the low-affinity HIR-B form is significantly increased in obese and NIDDM subjects compared with control subjects. In addition, the increased expression of the HIR-B isoform was significantly correlated with both body mass index (r = 0.52; p = 0.006) and fasting glucose levels (r = 0.59; p = 0.001). PMID- 7796987 TI - Molecular and linkage analysis of type-1 protein phosphatase catalytic beta subunit gene: lack of evidence for its major role in insulin resistance in Pima Indians. AB - Insulin resistance is believed to be a prediabetic condition that results from reduced rates of insulin-mediated glycogen synthesis in skeletal muscle. A decrease in activities of skeletal muscle glycogen synthase and of its regulatory enzyme type-1 protein phosphatase (PP 1) have been previously identified in insulin-resistant Pima Indians. Because the PP1 catalytic beta-subunit is presumed to be the major isoform in the glycogen-bound PP1 complex, we have selected the structural gene for this subunit (PPP1CB) as a candidate for a detailed genetic analysis. We have determined the exon-intron structure of PPP1CB, and have identified a polymorphic (CA)-repeat marker (D2S1237) at this gene. No sequence abnormalities were detected in PPP1CB by Southern blot analysis or by single-stranded conformational polymorphism analysis of all eight coding exons. Using sib-pair linkage analyses, no evidence for linkage was found between the D2S1237 marker at this locus and fasting insulin, insulin-stimulated glucose uptake in vivo, obesity, or non-insulin-dependent diabetes mellitus. Similarly, we have found no evidence for association of D2S1237 with any of these phenotypes. Based on our data we conclude that the structural gene for the PP1 catalytic beta-subunit does not appear to be a major genetic determinant responsible for the PP1 abnormalities characteristic of insulin resistance in Pima Indians. PMID- 7796986 TI - Association between left ventricular hypertrophy and erythrocyte sodium-lithium exchange in normotensive subjects with and without NIDDM. AB - The determinants of left ventricular mass in normal control subjects and subjects with non-insulin-dependent diabetes (NIDDM) are ill-defined. We therefore recorded M-mode and pulsed Doppler echocardiograms and 24-h ambulatory blood pressure in 57 normotensive subjects, 34 with NIDDM and 23 matched non-diabetic control subjects. Measurements of erythrocyte sodium-lithium counter-transport, plasma angiotensin II, plasma and platelet catecholamines and fasting plasma insulin were also made. Six control subjects (26%) and 15 diabetic subjects (44%) had some degree of left ventricular hypertrophy. Subjects with left ventricular hypertrophy (n = 21) had an elevated mean rate of sodium-lithium countertransport (0.40 +/- 0.13 vs 0.31 +/- 0.09 mmol.l-1.h-1; p < 0.01), parallel differences being observed in both the diabetic and control groups. Twelve of the subjects with left ventricular hypertrophy (57%) had elevated rates of sodium-lithium counter-transport compared to only seven (19%) of those without (p < 0.05). There was no consistent difference between those with and without left ventricular hypertrophy in any other clinical or biochemical variable. Multivariate analysis, with the presence or absence of left ventricular hypertrophy as the dependent variable, demonstrated that the maximal rate of sodium-lithium countertransport was the only variable that independently contributed to left ventricular hypertrophy (partial r = 0.35; F1.55 = 7.74; p = 0.007). This study demonstrates for the first time an association between left ventricular hypertrophy and erythrocyte membrane cation transport that is independent of hypertension, is present in both diabetic and non-diabetic groups, and may represent a link between elevated rates of membrane sodium transport and cardiovascular risk. PMID- 7796988 TI - The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers. AB - Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (< 300 microns internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6 +/- 1.6/70.0 +/- 1.5 mm Hg [mean +/- SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8% [p < 0.01], 1 mU/ml by 17% [p < 0.02] and 10 mU/ml by 22% [p < 0.01]). Sensitivity to insulin (ED50) only decreased at the highest concentration of insulin. However, acetylcholine-induced relaxation was not altered by insulin (Group 2). Time control studies (Group 3) showed that contractile and relaxation responses over the 4-h study period were unchanged. Furthermore, the length of time the vessels were exposed to insulin did not progressively impair responses (Group 4). These findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacerbate the abnormal haemodynamics observed in the capillary microcirculation of numerous vascular beds in diabetes. PMID- 7796989 TI - Skin capillary circulation severely impaired in toes of patients with IDDM, with and without late diabetic complications. AB - We have recently shown that the skin microcirculation of toes is significantly impaired in patients with diabetes and peripheral vascular disease, and this may be one major reason why these patients are highly susceptible to developing skin ulcers. The aim of the present study was to investigate whether the skin microcirculation is impaired also in diabetic patients free from macroangiopathy. One foot in each of 20 patients with insulin-dependent diabetes was investigated: 10 patients with and 10 patients without late complications. All patients had normal arterial circulation of their lower extremities. Two groups of age- and sex-matched healthy subjects served as controls. The capillary blood cell velocity in the nailfold of the great toe was investigated by computerised videophotometric capillaroscopy, and the total microcirculation within the same area evaluated by laser Doppler fluxmetry. The capillary blood cell velocity and the total skin microcirculation were studied during rest, and during postocclusive reactive hyperaemia. The total microcirculation was similar in patients and control subjects, whereas the capillary circulation was markedly reduced (p < 0.01) in the patients. The ratio between the capillary and total microcirculation was significantly decreased (p < 0.05-0.01) in the patients as compared to the control subjects, indicating a local maldistribution of blood in the skin microcirculation of the diabetic patients. The results of the present study show that in spite of a normal total skin microcirculation in the toes of insulin-dependent diabetic patients, both with and without late complications, the nutritional capillary circulation is severely impaired.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7796993 TI - Learning environmental and occupational medicine as a resident. PMID- 7796991 TI - Does NIDDM increase the risk for coronary heart disease similarly in both low- and high-risk populations? AB - Finland has marked regional differences in the occurrence of coronary heart disease (CHD). Although the causes for these differences in CHD mortality and morbidity in the Finnish population are unknown, it offers an excellent opportunity to investigate the effects of non-insulin-dependent diabetes mellitus (NIDDM) on CHD risk in two populations differing significantly with respect to the occurrence of CHD. Therefore, we carried out a 7-year prospective population based study including a large number of patients with NIDDM (East Finland: 253 men and 257 women; West Finland: 328 men, 221 women) and corresponding non diabetic subjects (East Finland: 313 men, 336 women; West Finland: 325 men, 399 women). In both study populations the presence of NIDDM increased significantly the risk for CHD events (CHD mortality or all CHD events including CHD mortality or non-fatal myocardial infarction). Diabetic men had 3-4 fold higher and diabetic women 8-11-fold higher risk for CHD than corresponding non-diabetic subjects. Both non-diabetic and diabetic subjects had odds ratios (East vs West) for CHD events of about 2 indicating a similar East-West difference in the CHD risk. Regional difference was quite similar in men and women. These results imply that factors related to NIDDM, independently of conventional risk factors and the occurrence of atherothrombosis in the background population, must play a major role in the pathogenesis of atherosclerotic vascular disease in NIDDM diabetes. PMID- 7796992 TI - Evaluation of a standardized hyperglucidic breakfast test in postprandial reactive hypoglycaemia. AB - The oral glucose tolerance test is not specific for diagnosing postprandial reactive hypoglycaemia, since it too frequently induces low blood glucose values in subjects who have never complained of symptoms of this. By contrast, the mixed meal tests are deceptive for this purpose because they do not induce hypoglycaemia in subjects who have complained of of hypoglycaemic symptoms. We investigated the frequency of hypoglycaemia after a standardized hyperglucidic breakfast test in three groups of subjects:group A, 43 control subjects; group B, 38 postprandial reactive hypoglycaemic patients; group C, 1193 asymptomatic subjects undergoing assessment of glycoregulation. In the 38 subjects with suspected reactive hypoglycaemia the mean blood glucose nadir was 3.48 +/- 0.08 mmol/l, i.e. lower than in control subjects (4.83 +/- 0.13 p < 0.0001). Blood glucose levels less than 3.3 mmol/l were found in 47.3% of subjects with suspected postprandial reactive hypoglycaemia (group B), i.e more frequently than in control subjects (group A: 2.2% p = 1.6 x 10(-6)) and asymptomatic subjects (group C: 1% p = 8 x 10(-22)). This markedly higher frequency of low blood glucose values in subjects with postprandial symptoms compared with control and asymptomatic subjects suggests that this test detects a tendency to hypoglycaemia after a standardized hyperglucidic breakfast. Since this test mimics average French eating habits, the results suggest that the patients undergo such symptoms in their everyday life, and that the hyperglucidic breakfast test is a simple alternative to ambulatory glucose sampling for diagnosis of postprandial reactive hypoglycaemia. PMID- 7796995 TI - International medical graduates series inspires readers' comments. PMID- 7796996 TI - International medical graduates series inspires readers' comments. PMID- 7796997 TI - International medical graduates series inspires reader's comments. PMID- 7796990 TI - Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease. AB - Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups. PMID- 7796994 TI - Debate journal club teaches critical appraisal skills. PMID- 7796998 TI - International medical graduates series inspires readers' comments. PMID- 7796999 TI - AFMO--leaders' foresight pays off. PMID- 7797000 TI - A family practice death. PMID- 7797002 TI - Family physicians and human rights: a case example from former Yugoslavia. AB - BACKGROUND: The role of family physicians in the protection of human rights is unclear. The purpose of this article is to explore this role through examination of the specific case of former Yugoslavia. METHODS: In January/February 1993, we investigated medical aspects of human rights abuses as part of a fact-finding mission for the Physicians for Human Rights organization. We used primarily qualitative methods, including direct observation, key informant interviews, focus groups, and key document review. RESULTS: We observed pervasive violations of medical neutrality, as indicated by the shelling of Kosevo Hospital, the major tertiary care hospital in Sarajevo. Forty-one percent of former prison camp detainees from north Bosnia housed at the Karlovac, Croatia, refugee camp had scars consistent with physical abuse. Civilians in north central Bosnia and Sarajevo were targeted through physical violence, artillery shelling, and strangulation of the public health infrastructure--food, water, electricity, heat, and medical supplies. CONCLUSIONS: Physicians can be uniquely useful in the investigation of human rights. The flexibility of family physicians and their attention to the biopsycosocial aspects of health can be especially useful. Family physicians should become actively involved in the protection of human rights. PMID- 7797001 TI - The importance of geriatrics to family medicine: a position paper by the Group on Geriatric Education of the Society of Teachers of Family Medicine. AB - The role of geriatrics and geriatricians in family medicine remains unsettled. Despite a rapidly aging population, a tremendous shortage now exists of faculty with interest and expertise in geriatrics. Relatively few family practice residents choose to enter geriatric fellowship programs, and federal funding for such programs has been reduced. Despite accreditation requirements, residency programs are not always able to provide the range of geriatric experiences needed to properly prepare graduates to provide care for the broad range of older patients. Medical students' exposure to geriatrics remains limited. The Group on Geriatric Education of the Society of Teachers of Family Medicine believes that family medicine faculty must recognize and be committed to the notion that geriatrics is integral to family medicine. Both undergraduate and residency training programs should emphasize experience with geriatric patients in multiple settings. In particular, the nursing home should not be the main focus of geriatric training. The small number of certified geriatric faculty will be able to provide leadership, but a broad range of faculty must become involved in teaching geriatrics. Faculty development activities and continuing education programs to foster the necessary expertise will be essential to the accomplishment of this task. PMID- 7797003 TI - Primary care specialty selection: application of a vocational behavior theory. AB - BACKGROUND AND OBJECTIVES: This study was designed to determine whether medical school graduates who completed undergraduate degrees in particular college majors were more likely to enter primary care residencies. John L. Holland's theory of vocational personalities and work environments was used to cluster undergraduate disciplines sharing distinctive qualities. These clusters were evaluated to determine if graduates from similar fields were more likely to pursue residencies in family practice, general internal medicine, or general pediatrics. METHODS: Students who graduated from US and Puerto Rican medical schools in 1987 were eligible for the study; college majors of 2,661 graduates entering primary care specialties were analyzed. RESULTS: Students completing undergraduate studies in the following majors selected primary care residencies by a twofold difference over the expected frequency: agriculture, black studies, civil engineering, general studies, literature, occupational therapy, and speech. Chi-square tests revealed no differences across Holland types in the frequency with which science and nonscience students selected primary care residencies. CONCLUSIONS: Primary care specialties tend to accommodate students from varied academic backgrounds and appear to be tolerant of individuals who have completed undergraduate course work in either bioscientific or biosocial nonscience disciplines. PMID- 7797004 TI - An educational intervention to increase faculty publication productivity. AB - BACKGROUND: Writing is an essential skill for academic family physicians. It is essential in all of the academic physicians' roles, and publications are critical for promotion and tenure. This study describes a three-part faculty development instructional program designed to teach writing skills. The instructional program was repeated over a 3-year period involving two different institutions with departments of family medicine. METHODS: Educational interventions included seminars, workshops, and independent practice, with feedback from senior advisors. The practice and feedback sections centered on the faculty members' own written products. RESULTS: This series resulted in the publication of 16 papers from 13 of the 40 faculty participants. CONCLUSIONS: Our experience suggests that a writing series is one effective method that departments of family medicine may use to facilitate the writing productivity of faculty. PMID- 7797006 TI - Beliefs and attitudes of persons with diabetes. AB - BACKGROUND AND OBJECTIVES: Physicians seem to agree that noncompliance by diabetic patients is a problem. Despite this, there have been few qualitative studies on the actual behaviors, beliefs, and attitudes of diabetic patients. The present study was conducted to explore these parameters to help discover ways that physicians might enhance diabetic patients' compliance. METHODS: This research used a variation of grounded qualitative theory to assess the beliefs and attitudes of 14 non-insulin, adult-onset diabetic patients with a disease duration of at least 3 years. Of these, seven were considered compliant and seven noncompliant by their primary physician. RESULTS: Most of the patients felt they had a good understanding of diabetes, were compliant with their medical regimen, and considered diabetes a serious disease. Although many of the patients expressed strong emotions of frustration and anger, a majority felt that diabetes had led them to a healthier and/or happier lifestyle. Noncompliant patients were more likely to believe that diabetes would not affect the eventual outcome of their lives. They were less likely to want no further information from their physician and less likely to report following their physician's instructions. CONCLUSIONS: A better understanding of patients' beliefs and attitudes may help physicians increase motivation, understanding, and compliance of diabetic patients. PMID- 7797007 TI - Small area variation analysis: a tool for primary care research. AB - Small area variation analysis is a research tool used by health services researchers to describe how rates of health care use and events vary over well defined geographic areas. Significant variation has been shown to exist in the rates of hospitalization for chronic obstructive lung disease, pneumonia, hypertension, and in surgical procedures, such as hysterectomy, cholecystectomy, and tonsillectomy. Potential sources of variation include differences in underlying morbidity, access to care, physician judgment, quality of care delivered, patient demand for services, and random variation. Small area variation studies have been used to determine if significant variation exists across geographic areas and to describe relationships between the observed variation and potential causal factors. Methodologic concerns include the definition of small areas, defining the at-risk population within each small area, sample size, case mix adjustments, and stability of rates over time. The use of small area analysis in primary care will require definition of appropriate small areas for ambulatory care, description of the variation in ambulatory events across small areas, development of appropriate measures for ambulatory case mix, and development of appropriate tools to measure the outcomes of ambulatory care. PMID- 7797005 TI - Implementation and evaluation of a computer-based preventive services system. AB - BACKGROUND AND OBJECTIVES: Insufficient attention has been paid to the role that modern information systems can play in improving the delivery of and education about preventive services in family medicine training and practice sites. From September 1990-September 1993, the Department of Family Medicine at the Medical University of South Carolina conducted a demonstration project designed to develop, implement, and evaluate a comprehensive, computer-based preventive services delivery and educational system, based on the recommendations in the US Preventive Services Task Force (USPSTF) Report. METHODS: A computer-based patient record (CPR) system was implemented. The system had sophisticated preventive services tracking and reminder, physician, and patient education features. Twenty nine basic USPSTF recommendations were incorporated in the system. An extensive physician education series was also implemented. A multi-method evaluation system, including patient exit surveys, physician interviews, and practice audits was used to evaluate and design improvements to the CPR and education systems. RESULTS: Although the system initially had no effect on patient perceptions about the frequency of preventive services delivery, there was reasonable concordance between patient desires and physician behavior for the discussion of preventive services (Kappa = .5 to .6). Physician acceptance of the system was good--in 1992, 30% of physicians used the preventive services reminders in most of their patient visits, and in 1993, 88% of physicians reported more frequent use. Practice audits from February 1992-July 1993 showed increased adherence with all seven counseling services, 10 of 15 screening services, and one of five immunization services. CONCLUSIONS: A CPR-based preventive services system coupled with an adaptable physician education about and delivery of preventive services. an ideal solution to improving the education about and delivery of preventive services. PMID- 7797008 TI - Family medicine and human rights. PMID- 7797009 TI - Oral immunization with Helicobacter pylori urease B subunit as a treatment against Helicobacter infection in mice. AB - BACKGROUND & AIMS: Eradication of Helicobacter pylori infections in humans results in the healing of gastritis and gastric ulcers. This study used a mouse model to test whether oral vaccination can cure Helicobacter infection and gastritis. METHODS: Mice were infected with Helicobacter felis. Three weeks after infection, the mice were orally immunized with H. pylori urease B subunit. Control mice were simultaneously infected but sham immunized. RESULTS: Three to 8 weeks after oral immunization of H. felis-infected mice with recombinant H. pylori urease B subunit, the infection cleared and there was no evidence of gastritis. Vaccinated mice remained protected against two consecutive H. felis challenges. CONCLUSIONS: These results show that the lack of natural immunity against Helicobacter can be overcome by oral immunization and that vaccination offers a novel therapeutic approach to Helicobacter-induced gastritis. PMID- 7797010 TI - Bone mass and metabolism in patients with celiac disease. AB - BACKGROUND & AIMS: Several aspects of the pathogenesis of osteopenia in celiac disease are still unclear. Therefore, bone mass and metabolism were evaluated in adults with celiac disease in a cross-sectional study. METHODS: Bone mineral density (BMD), assessed by total body dual-photon absorptiometry, and serum indices of bone metabolism and remodeling were evaluated in 17 patients with untreated celiac disease, 14 with celiac disease on a gluten-free diet, and 24 healthy volunteers. RESULTS: BMD, expressed as a z score, was significantly lower in patients with untreated celiac disease than in patients with treated celiac disease and volunteers and lower in patients with treated celiac disease than in volunteers. Similar changes were observed in serum calcium level, whereas intact parathyroid hormone level was significantly higher in untreated than in treated patients with celiac disease and volunteers, and no difference was found between the latter two groups. 25-Vitamin D level was significantly lower and 1,25 vitamin D level significantly higher in untreated celiac disease than in treated celiac disease and volunteers. Indices of bone remodeling were significantly higher in untreated than in treated patients and volunteers and significantly and positively correlated with iPTH in untreated patients with celiac disease. CONCLUSIONS: BMD is almost invariably low in patients with untreated celiac disease. Results in treated patients suggest that gluten-free diet improves but does not normalize BMD. Untreated celiac disease is characterized by high levels of 1,25-vitamin D and by increased bone turnover, caused by the increase in intact parathyroid hormone level. PMID- 7797011 TI - Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). AB - BACKGROUND & AIMS: Increased concentrations of tumor necrosis factor (TNF), a potent proinflammatory cytokine, can be shown in the mucosa of patients with active Crohn's disease. Neutralization of TNF has been shown to decrease recruitment of inflammatory cells and granuloma formation in several animal models. The aim of this study was to investigate the safety and potential efficacy of an anti-TNF monoclonal antibody in the treatment of active Crohn's disease. METHODS: Ten patients with active Crohn's disease that was unresponsive to therapy were administered a single infusion of an anti-TNF human/mouse chimeric monoclonal antibody (cA2) in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. RESULTS: Eight patients showed normalization of Crohn's Disease Activity Index scores and healing of ulcerations as judged by colonoscopy within 4 weeks after treatment. One patient had a perforation after colonoscopy and recovered completely after surgery. One elderly patient showed a poor response. The average duration of response after a single infusion was 4 months. No adverse experiences related to cA2 were observed. CONCLUSIONS: The results support the hypothesis that TNF is of major importance in the pathogenesis of Crohn's disease. Treatment with cA2 was safe and may be useful in patients with Crohn's disease that is unresponsive to steroid treatment. PMID- 7797012 TI - Morphological factors influencing transepithelial conductance in a rabbit model of ileitis. AB - BACKGROUND & AIMS: Infection of rabbits with coccidia (Eimeria magna) causes chronic ileal inflammation and diarrhea. Inflamed ileum also shows decreased transmural conductance. The aim of this study was to characterize morphological factors known to affect paracellular permeability that may alter transmural conductance in inflamed ileum. METHODS: Ileal mucosa was mounted in Ussing chambers for study of [3H]mannitol and [3H]inulin fluxes. Light and electron microscopy were used for morphometric studies. Alterations in the zonula occludens of epithelial cells were evaluated in freeze-fracture replicas. RESULTS: Inflamed ileum showed diminished paracellular fluxes. Inoculated rabbits showed marked lymphoplasmocytic infiltration and villus blunting in ileum. Villus linear junctional density was unaffected. However, total villus apical surface area per square centimeter of tissue was reduced in inflamed ileum, causing a diminished total villus linear junctional pathway per square centimeter of apical surface. Villus zonula occludens strand number was reduced in inflamed ileum, whereas the frequency of both villus and crypt lateral surface extrajunctional strands increased. CONCLUSIONS: Chronic inflammation exerts a profound effect on ileal paracellular permeability. Morphological data suggest that this effect may be caused in part by alterations in inflamed ileal mucosal structure and tight junctional organization and density, particularly on villi. PMID- 7797013 TI - Spontaneous intestinal inflammation and nitric oxide metabolism in HLA-B27 transgenic rats. AB - BACKGROUND & AIMS: It has been reported that transgenic rats expressing the HLA B27 and the beta 2- microglobulin genes develop spontaneous gastrointestinal (GI) inflammation; however, no systematic or quantitative evaluation of this GI inflammation has been reported. Therefore, the objective of this study was to characterize quantitatively the GI injury and inflammation observed in commercially available HLA-B27 transgenic rats. METHODS: HLA-B27 rats and Fisher 344 male controls were used for these studies. Gastric, ileal, and colonic blood to-lumen clearances of 51Cr-ethylenediaminetetraacetic acid, tissue myeloperoxidase activities, and wet/dry ratios of the various tissues as well as plasma nitrate and nitrite levels were quantified for each control and transgenic animal. RESULTS: Spontaneous ileitis and colitis developed in 5 of 10 HLA-B27 transgenic rats beginning at approximately 17 weeks of age and persisting for an additional 13 weeks. Increases in mucosal permeability and myeloperoxidase activities as well as histological analysis showed intestinal injury and chronic inflammation. Plasma levels of nitrate and nitrite, the stable decomposition products of nitric oxide, were found to be significantly enhanced (fourfold) only in those rats that developed the intestinal inflammation. CONCLUSIONS: The chronic ileitis and colitis observed in HLA-B27 transgenic rats seems to be associated with enhanced NO metabolism. PMID- 7797014 TI - A germline substitution in the human MSH2 gene is associated with high-grade dysplasia and cancer in ulcerative colitis. AB - BACKGROUND & AIMS: The DNA mismatch repair gene human MSH2 shows a germline mutation in certain family members with hereditary nonpolyposis colorectal cancer. There is an increased risk of colorectal cancer in patients with ulcerative colitis (UC) with extensive disease of > 8 years' duration; however, specific constitutional predisposing genetic abnormalities have not yet been identified. METHODS: A germline human MSH2 abnormality was sought in patients with UC with high-grade dysplasia or carcinoma. RESULTS: After direct sequencing of exon 13 and flanking regions of human MSH2, a germline T to C substitution was shown at the -6 intronic splice acceptor site of exon 13. This substitution was found in 14 of 53 patients with UC with high-grade dysplasia or carcinoma (26%) compared with 4 of 36 high-risk patients with UC without dysplasia or cancer (11%) (P < or = 0.04) and in 7 of 80 healthy adult blood donors (9%) (P < or = 0.003). The patients with UC who had the substitution were three times more likely to develop neoplasia than patients with UC who did not carry it. CONCLUSIONS: An intronic splice-site substitution in the human MSH2 gene is present in the general population but may predispose to cancer in the setting of UC. PMID- 7797015 TI - Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice. AB - BACKGROUND & AIMS: The injection of mice with anti-CD3 monoclonal antibody causes activation of T lymphocytes and leads to a lethal shock syndrome. The aim of this study was to investigate T cell-dependent, cytokine-mediated target cell death that leads to organ injury. METHODS: Anti-CD3 monoclonal antibody or staphylococcal enterotoxin B was injected into mice sensitized by D galactosamine. Liver injury was assessed biochemically and histologically, and circulating cytokines were determined. RESULTS: Mice sensitized with D galactosamine developed severe liver injury within 8 hours after injection of anti-CD3 monoclonal antibody or staphylococcal enterotoxin B. Apoptotic bodies and chromatin condensation were detectable 5 hours after anti-CD3 monoclonal antibody challenge. DNA fragmentation in the liver preceded the increase in plasma alanine aminotransferase activity. Anti-CD3 monoclonal antibody induced the release of tumor necrosis factor and other cytokines. Passive immunization against tumor necrosis factor or pretreatment with immunosuppressive drugs protected mice from liver injury. Liver injury associated with apoptotic cell death and DNA fragmentation was also noted in D-galactosamine-sensitized mice injected with staphylococcal enterotoxin B. CONCLUSIONS: Tumor necrosis factor induced hepatic apoptosis followed by necrosis may represent a general pathomechanism of T-cell shock models using D-galactosamine-sensitized mice. PMID- 7797017 TI - Role of Kupffer cells in cold ischemia/reperfusion injury of rat liver. AB - BACKGROUND & AIMS: Kupffer cell activation is hypothesized to play an etiopathogenic role in storage-related graft failure after liver transplantation. The aim of this study was to verify whether the elimination of Kupffer cells modifies the magnitude of cold ischemia/reperfusion injury of the liver. METHODS: Rat Kupffer cells were eliminated by an intravenous injection of liposome encapsulated dichloromethylene diphosphonate. Livers from control and treated rats were isolated and perfused before and after 24-hour cold ischemia in the University of Wisconsin solution (4 degrees C). Hepatocyte and sinusoidal endothelial cell functions were evaluated by taurocholate and hyaluronic acid elimination, respectively. Liver transplantation was also performed using control and treated donor livers stored under identical conditions. RESULTS: Compared with baseline values, similar alterations were found in both groups after cold ischemia for hepatocyte function (intrahepatic resistance, bile secretion, lactate dehydrogenase release, oxygen consumption, and taurocholate intrinsic clearance) and for sinusoidal endothelial cell function (hyaluronic acid intrinsic clearance). The 10-day survival rate of animals undergoing transplantation was not different between the groups (6 of 15 vs. 4 of 15, control vs. treated donor livers, respectively). CONCLUSIONS: The presence or absence of Kupffer cells does not modify the effect of 24-hour cold ischemia/reperfusion on the rat liver. PMID- 7797016 TI - Screening blood donors for hereditary hemochromatosis: decision analysis model based on a 30-year database. AB - BACKGROUND & AIMS: The high prevalence, morbidity, premature death, and benefit of early diagnosis and treatment make hemochromatosis a prime target for screening in the white population. Decision analysis techniques were used to compare the outcome, utility, and incremental cost savings of a plan to screen voluntary blood donors for hemochromatosis. METHODS: The screening strategy includes sequential testing of serum unsaturated iron-binding capacity, serum transferrin saturation, serum ferritin, and either hepatic iron index or venesections to measure exchangeable body iron. Estimates of prevalence, asymptomatic intervals, probabilities of life-threatening clinical complications, symptom-specific life expectancy, and sensitivity and specificity of screening tests are based on our database of 170 hemochromatosis homozygotes and the published literature. RESULTS: The screening strategy led to an incremental increase in utility of 0.84 quality-adjusted life days with an incremental cost savings of $3.19 per blood donor screened. When the potential of identifying asymptomatic homozygous siblings was included, these values increased to 1.18 quality-adjusted life days and $12.57 per person screened. Screening remained a dominant strategy given a prevalence of hemochromatosis of > 0.0026 or an initial screening test cost of < $8. CONCLUSIONS: Screening blood donors for hemochromatosis has the potential to improve overall societal health status and decrease third-party payer health care costs over the long-term. PMID- 7797018 TI - Pretranslational down-regulation of cytochromes P450 2C11 and 3A2 in male rat liver by tumor necrosis factor alpha. AB - BACKGROUND & AIMS: The cytokine tumor necrosis factor alpha (TNF-alpha) is a primary inflammatory mediator after liver injury. Several cytokines impair the regulation of cytochrome P450 (CYP) genes in liver, but the specificity of these effects remains unclear. This study investigated the effects of recombinant murine TNF-alpha on the expression of specific constitutive CYPs in male rat liver. METHODS: Microsomal steroid hydroxylation was used to indicate the activities of specific CYPs after TNF-alpha treatment and immunoblotting to correlate CYP activities with protein contents. CYP messenger RNA levels were measured by solution hybridization. RESULTS: Testosterone 2 alpha/16 alpha- and 6 beta-hydroxylations, mediated respectively by CYPs 2C11 and 3A2, were decreased after TNF-alpha treatment, whereas 7 alpha-hydroxylation (CYP 2A1) was unchanged. Similarly, progesterone 2 alpha/16 alpha- (CYP 2C11) and 6 beta-hydroxylations (CYP 3A2), but not 21-hydroxylation (CYP 2C6), were decreased after TNF-alpha treatment. 2C11 and 3A2 apoproteins and messenger RNAs, but not 2A1 apoprotein, were decreased after TNF-alpha treatment; changes in messenger RNAs were evident 4 hours after treatment. CONCLUSIONS: TNF-alpha down-regulates CYPs 2C11 and 3A2 in male rat liver at a pretranslational level, whereas two other constitutive CYPs, 2A1 and 2C6, seem refractory to TNF-alpha. Thus, impaired CYP regulation by TNF-alpha resembles the combined effects of autologous interferons (on 3A2) and interleukins (on 2C11). PMID- 7797020 TI - Evidence for autoregulation of cholecystokinin secretion during diversion of bile pancreatic juice in rats. AB - BACKGROUND & AIMS: The mechanism regulating cholecystokinin (CCK) secretion during prolonged diversion of bile pancreatic juice (BPJ) is unknown. We examined the hypothesis that the decrease of plasma CCK levels after prolonged diversion of BPJ is mediated by an increase in plasma somatostatin levels evoked by hypercholecystokinemia and somatostatin in turn inhibits CCK-releasing peptide (CCK-RP) bioactivity and decreases plasma CCK levels. METHODS: Pancreatic secretion, plasma CCK levels, and somatostatin levels were monitored for 7 hours after diversion of BPJ in anesthetized rats. Secretion of CCK-RP bioactivity during diversion of BPJ was examined in the presence or absence of somatostatin. RESULTS: Diversion of BPJ for 2 hours caused a 13- and 2.5-fold increase in plasma CCK and somatostatin levels. The increase in somatostatin levels was blocked by the CCK antagonist L364,718. At 5 hours after diversion of BPJ, plasma CCK and somatostatin levels and luminal CCK-RP bioactivity decreased to basal levels. The decrease in plasma CCK levels was prevented by the administration of a specific somatostatin antagonist. We also showed that the stimulatory effect of the CCK-RP bioactivity was eliminated when the donor rat was pretreated with somatostatin. CONCLUSIONS: Autoregulation of CCK secretion occurs during the diversion of BPJ and this is mediated by somatostatin, which inhibits the secretion of CCK-RP bioactivity and decreases plasma CCK levels. PMID- 7797021 TI - Up-regulation of transforming growth factor alpha binding sites in experimental rabbit colitis. AB - BACKGROUND & AIMS: Transforming growth factor alpha (TGF-alpha), a member of the epidermal growth factor family, has been proposed to mediate protection against mucosal injury and promote healing of the gastrointestinal mucosa. TGF-alpha acts via a plasma membrane receptor, which is distributed throughout the digestive system with the highest density in epithelia. The aim of this study was to investigate the pattern of TGF-alpha binding sites in the normal and inflamed rabbit colon. METHODS: The immune complex/formalin model of acute colitis and tissue section receptor autoradiography were used. Inflammation was characterized by cellular infiltration, edema, and necrosis. TGF-alpha binding relative density was determined by densitometry on film autoradiograms. RESULTS: The normal colon had a low to moderate density of specific TGF-alpha binding sites in the mucosa and external muscle. TGF-alpha binding density was significantly increased in the mucosa at 4 hours and remained higher than normal for up to 48 hours. The density of binding sites in the mucosa and the inflammatory index returned to near normal values at 96 hours, when colitis had subsided. CONCLUSIONS: The increase in TGF alpha binding in the mucosa during experimental colitis supports the hypothesis that members of the epidermal growth factor family play a role in inflammation, perhaps acting as mediators of mucosal protection and repair. PMID- 7797022 TI - Pancreatitis is a risk factor for pancreatic cancer. AB - BACKGROUND & AIMS: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges since 1970. In taking advantage of this large database, the present study aimed to determine whether pancreatitis is a risk factor for pancreatic cancer. METHODS: A case control study compared the occurrence of pancreatitis in 2639 patients with pancreatic cancer and a matched control group of 7774 subjects using multivariate conditional logistic regression. RESULTS: The odds ratio associated with pancreatitis increased from 2.04 (95% confidence interval [CI], 1.53-2.72) 7 or more years before the first diagnosis of cancer to 2.14 (CI, 1.68-2.72) 3 or more years before cancer diagnosis and to 2.31 (CI, 1.87-2.86) 1 or more years before cancer diagnosis. In a multivariate analysis, all types of pancreatitis or chronic pancreatitis alone were associated with a significant risk, their odds ratios being 3.42 (CI, 1.98 5.91) and 2.23 (CI, 1.43-3.49), respectively. No influence was exerted by other variables, such as history of gallstone disease or alcoholism, frequency of hospital discharges with pancreatitis, and length of coverage in the VA system. CONCLUSIONS: A history of pancreatitis constitutes a significant risk for subsequent development of pancreatic cancer. The increase of the risk with decreasing time before the diagnosis of cancer may indicate that a fraction of pancreatic cancers are initially misdiagnosed as pancreatitis. PMID- 7797019 TI - Aquaretic effect of the kappa-opioid agonist RU 51599 in cirrhotic rats with ascites and water retention. AB - BACKGROUND & AIMS: It has recently been described that kappa-opioid receptor agonists inhibit antidiuretic hormone secretion and promote water excretion in humans and experimental animals. The aim of this study was to evaluate the aquaretic efficacy of the kappa-opioid receptor agonist RU 51599 in conscious cirrhotic rats with ascites and water retention. METHODS: In protocol 1, arterial pressure, heart rate, and renal water metabolism were measured in basal conditions and then were measured for 120 minutes after the administration of Ringer's solution (n = 8; 0.4 mL) or RU 51599 (n = 7; 1 mg/kg). In protocol 2, plasma antidiuretic hormone concentration was measured (n = 6) before and 60 minutes after administration of RU 51599 (1 mg/kg). In protocol 3, the effect of RU 51599 (n = 9; 1 mg/kg) was compared with that of the V2-receptor antagonist SKF 100398 (n = 9; 30 micrograms/kg). RESULTS: RU 51599 administration induced a profound diuretic and aquaretic effect without altering arterial pressure and heart rate. In protocol 2, the kappa-opioid agonist reduced by about 50% plasma antidiuretic hormone levels (from 6.6 +/- 0.9 to 3.4 +/- 0.6 pg/mL; P < 0.05). Finally, the improvement in renal water metabolism induced by RU 51599 was similar to that produced by the V2-receptor antagonist. CONCLUSIONS: RU 51599 has a potent aquaretic effect in cirrhotic rats with water retention, suggesting that kappa-opioid receptor agonists may be useful for the treatment of water retention and dilutional hyponatremia in cirrhosis. PMID- 7797023 TI - The role of endoscopic retrograde cholangiopancreatography in patients with laparoscopic cholecystectomies. AB - BACKGROUND & AIMS: The best clinical strategy for using endoscopic retrograde cholangiopancreatography (ERCP) with laparoscopic cholecystectomy is unknown. The aim of this study is to use decision analysis to assess four different approaches to using ERCP in patients undergoing laparoscopic cholecystectomy. METHODS: Decision trees were designed for four clinical strategies: (1) preoperative ERCP, with sphincterotomy for choledocholithiasis; (2) selective preoperative ERCP for patients at high risk for choledocholithiasis, choledocholithiasis found at surgery treated by postoperative ERCP; (3) no preoperative ERCP, choledocholithiasis detected intraoperatively treated by postoperative ERCP; and (4) no preoperative ERCP, choledocholithiasis detected intraoperatively treated with open common bile duct exploration. Using decision analysis with literature derived data, the impact on outcome parameters was calculated. RESULTS: Postoperative ERCP resulted in the lowest cost, procedure numbers, and hospital and back-to-work days. With high preoperative likelihood of choledocholithiasis, selective preoperative ERCP was probably a clinically equivalent strategy. Sensitivity analysis supported these conclusions when the probabilities and utilities were varied over a wide range. The open operative approach to choledocholithiasis was only favored if ERCP had < 75% diagnostic and < 50% therapeutic success rates or lengthened hospitalization by > 7 days. CONCLUSIONS: This study suggests that performing ERCP after laparoscopic cholecystectomy minimizes costs and morbidity; however, when choledocholithiasis is likely, selective preoperative ERCP may be a clinically equivalent strategy. PMID- 7797025 TI - Hyperammonemic coma due to parenteral nutrition in a woman with heterozygous ornithine transcarbamylase deficiency. AB - Ornithine transcarbamylase deficiency is an X-linked disorder of the urea cycle that can cause hyperammonemic encephalopathy in hemizygous males and heterozygous females. Affected females typically limit protein intake in their diet. This case report describes a 36-year-old woman with ulcerative colitis who went into hyperammonemic coma after administration of total parenteral nutrition. A similar episode of coma had occurred 7 years earlier after she delivered a normal boy. Heterozygous ornithine transcarbamylase deficiency was diagnosed based on a positive allopurinol tolerance test result after elevated levels of plasma glutamine and low plasma citrulline were detected. The protein load associated with parenteral alimentation resulted in symptomatic expression of this partial enzyme deficiency in this unique case. Partial ornithine transcarbamylase deficiency must always be considered in adult women and men with hyperammonemia who have normal liver function test results. PMID- 7797026 TI - Eicosanoids and the gastrointestinal tract. AB - Determining the role of eicosanoids in gastrointestinal physiology and pathophysiology has been an active area of investigation over the past 20 years. The landmark discovery of prostaglandin endoperoxide synthase and other enzymes involved in the production of arachidonic acid products (lipoxygenases and epoxygenases) ushered in a new era of research. The goal of this review is to distill a large body of work pertaining to studies of eicosanoids in the gastrointestinal tract. This review has been organized according both to functional (secretion and motility) and disease-related (inflammation, mucosal injury, and neoplasia) effects. The aim of this article is to present a clear summary of this area of gastroenterology so that future research can be directed in a logical and productive manner. PMID- 7797027 TI - Production of immunoglobulin G and G1 antibodies to cytoskeletal protein by lamina propria cells in ulcerative colitis. AB - BACKGROUND & AIMS: Recent studies suggest an autoantigenic role for tropomyosin related protein(s) in ulcerative colitis (UC). This study examined whether immunoglobulin G and G1 subclass antibodies against tropomyosins are produced spontaneously by the lamina propria mononuclear cells (LPMCs) that infiltrate the inflamed UC tissue. METHODS: LPMCs were isolated from colonic biopsy specimens from 29 patients with UC, 15 with colonic Crohn's disease (CD), and 13 with non inflammatory bowel disease (IBD). The autologous peripheral blood mononuclear cells (PBMCs) were obtained. Cells were cultured in vitro and unstimulated for 10 days. Spontaneous production of immunoglobulin G and G1 antibodies against tropomyosins was measured by enzyme-linked immunosorbent assays using highly enriched tropomyosins from skeletal muscle and colonic mucosa. RESULTS: The total immunoglobulin G produced by LPMCs from both patients with UC and CD was comparable but higher than from patients with non-IBD (P < 0.05). However, immunoglobulin G antibodies to tropomyosins were higher in patients with UC than in patients with CD (P < 0.04) and non-IBD (P < 0.02). LPMCs from patients with symptomatic UC produced higher immunoglobulin G antibodies to tropomyosins than patients with UC in remission (P < 0.03), symptomatic CD (P < 0.04), and non-IBD (P < 0.02). Immunoglobulin G antibodies to tropomyosins predominantly belonged to immunoglobulin G1 subclass. The autologous PBMCs showed comparable results. CONCLUSIONS: Immunoglobulin G antibodies predominantly belonging to immunoglobulin G1 subclass and reactive against tropomyosin-related protein(s) are spontaneously produced by LPMCs from the colonic mucosa in patients with UC. PMID- 7797028 TI - A primer on outcomes research for the gastroenterologist: report of the American Gastroenterological Association task force on outcomes research. PMID- 7797031 TI - Screening for hemochromatosis. PMID- 7797029 TI - Autoimmunity and ulcerative colitis: can two enigmas make sense together? PMID- 7797030 TI - Helicobacter pylori: a diagnostic dilemma and a dilemma of diagnosis. PMID- 7797024 TI - Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells. AB - BACKGROUND & AIMS: Hypersecretion of gallbladder mucin has been proposed as a pathogenic factor in gallstone formation. We investigated whether mucin secretion is modulated by biliary constituents using normal, well-differentiated dog gallbladder epithelial cells. METHODS: Model biles or bile salts were applied to monolayers of epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labeled glycoproteins. RESULTS: Model biles with different cholesterol saturation indices increased mucin secretion by the cells to an average 251% after 5 hours of incubation (P < 0.01). Mucin secretion remained elevated during a 24-hour period, suggesting a sustained effect on mucin secretion. There was no relation between the cholesterol or phospholipid concentration and the extent of stimulation of mucin secretion. Taurocholate caused a dose-dependent increase in mucin secretion, suggesting that bile salt was the bile component responsible for the stimulatory effect. At a concentration of 0.5 mmol/L, only the more hydrophobic bile salts taurochenodeoxycholate and taurodeoxycholate, but not the hydrophylic bile salts taurocholate and tauroursodeoxycholate, stimulated mucin secretion (P < 0.01). CONCLUSIONS: Bile salts play an important role in the regulation of mucin secretion. A shift in the bile salt composition of bile towards the more hydrophobic bile salts may cause mucin hypersecretion, thereby initiating cholesterol gallstone formation. PMID- 7797032 TI - Motor cycles and other cycles in chronic pancreatitis. PMID- 7797033 TI - Erythromycin enhances fasting and postprandial proximal gastric tone in humans. AB - BACKGROUND & AIMS: Low doses of erythromycin induce antral contractions and accelerate gastric emptying. However, the effect of erythromycin on the proximal stomach remains unknown. The aim of this study was to assess the effect and mechanism(s) of action of erythromycin on proximal gastric tone in humans. METHODS: Gastric tone was measured using an electronic barostat in two groups of 6 subjects both in the fasting state and after a 200-kcal meal. On different occasions, subjects received saline, atropine alone (6 micrograms.kg-1.h-1 for 30 minutes), erythromycin alone (1.5 mg/kg in the fasting state and 1.5 and 3.0 mg/kg in the postprandial state), and erythromycin plus atropine. RESULTS: Low dose (1.5 mg/kg) erythromycin enhanced fasting gastric tone, but only the 3.0 mg/kg dose reduced the duration of meal-induced relaxation (37 +/- 14 vs. 105 +/- 20 minutes; P < 0.01). Atropine did not change the fasting or postprandial gastric tone as well as the erythromycin-induced responses. Plasma motilin levels were unaffected by erythromycin infusion. No correlation was observed between gastric tone and plasma motilin or erythromycin levels. CONCLUSIONS: Erythromycin enhances fasting and postprandial proximal gastric tone in humans by a mechanism that does not seem to involve endogenous motilin release or a cholinergic pathway. PMID- 7797034 TI - Management of choledocholithiasis in the laparoscopic era. PMID- 7797036 TI - Eradication of Helicobacter pylori: in search of a regimen the patient may accept. PMID- 7797035 TI - Antibiotics and cholangitis. PMID- 7797037 TI - Gastrointestinal sensory function in functional dyspepsia. PMID- 7797038 TI - Hexamethonium and secretory diarrhea. PMID- 7797039 TI - Portal hypertensive vasculopathy and mucosal vascular ectasias. PMID- 7797040 TI - Cure of gastric lymphoma with antibiotics. PMID- 7797041 TI - Altered rectal perception is a biological marker of patients with irritable bowel syndrome. AB - BACKGROUND & AIMS: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. METHODS: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. RESULTS: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. CONCLUSIONS: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS. PMID- 7797042 TI - Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer. AB - BACKGROUND & AIMS: Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in hereditary nonpolyposis colon cancer (HNPCC). However, nonneoplastic tissues from patients inheriting defects in human MSH2 or human MLH1 do not show significant genetic instability. The aim of this study was to determine whether acquisition of genetic instability at the adenoma stage promotes malignant transformation by studying adenoma carcinoma progression in HNPCC. METHODS: Dinucleotide repeat loci were analyzed by polymerase chain reaction from microdissected adenoma and/or carcinoma stages from formalin-fixed paraffin-embedded HNPCC tumors. RESULTS: Although genetic instability was observed at some loci in almost all cases, the proportion of microsatellite loci altered was significantly less (P < 0.01) in completely benign adenomas (24%) than in benign areas of adenomas with malignancy (54%). Molecular fingerprints indicated intratumor heterogeneity, with evolution of related subclones of neoplastic cells. However, in all cases of tumor progression, at least one subclone from the adenoma stage was closely related to the carcinoma. CONCLUSIONS: Some genetic instability develops at the benign adenoma stage in most HNPCC tumors. Adenomas with a greater rate of genetic instability are more likely to progress to carcinoma. Topographic genotyping data provides evidence supporting the hypothesis of adenoma-carcinoma progression in HNPCC. PMID- 7797043 TI - Endogenous bacterial toxins are required for the injurious action of platelet activating factor in rats. AB - BACKGROUND & AIMS: Platelet-activating factor (PAF), an endogenous mediator for experimental sepsis, has been shown to induce shock and intestinal necrosis in vivo. However, it is unclear whether PAF exerts its injurious effects on the intestinal tissue directly or via synergism with other endogenous products. The aim of this study was to examine the role of endogenous bacterial products, such as endotoxin, in PAF-induced intestinal injury. METHODS: PAF (3 micrograms/kg) was injected intravenously into normally colonized rats, germfree rats, and normal rats pretreated with a combination of antibiotics, and the systemic response and intestinal injury were assessed. RESULTS: PAF did not cause prolonged shock, leukopenia, hemoconcentration, and bowel necrosis in germfree rats. When germfree rats were primed with a low dose (0.5 mg/kg) of endotoxin, the protection was lost. Combined treatment of the normally colonized rats with neomycin, polymyxin B, and metronidazole for 7 days largely protected the animal from PAF-induced shock and intestinal necrosis. CONCLUSIONS: PAF does not directly induce prolonged hypotension, hemoconcentration, persistent leukopenia, and gross intestinal necrosis but causes these changes via a synergism with endogenous bacterial toxins, presumably from the gut flora. PMID- 7797045 TI - State-of-the-art potential clamp device for myelinated nerve fibres using a new versatile input probe. AB - A potential clamp device for myelinated axons is presented which, for the first time, systematically optimizes all the methodological parameters that limit the reliability of ionic current measurements. A crucial step toward this end consisted in the development of a new input probe with broad-band, extremely low capacitance characteristics. In combination with a simple-to-use compensation criterion for optimum positive feedback, based on plausible assumptions, and with additional technological improvements, it enables the measurement of ionic currents with a reliability never previously achieved. The consequences with respect to evaluation of several earlier findings are discussed. PMID- 7797044 TI - A simulation approach to the two-point stochastic model of olfactory neurons. AB - Neurons need two basic properties to carry out their functions. The first is their ability to transduce the changes of the dendritic potential and to sum them in spatial and temporal dimensions. The second is their ability to elicit an action potential which can be transmitted along the axon at a long distance. This simulation study demonstrates how these two properties can be retracted to the two points of the neuron model. First we discussed the definition and general properties of the so-called two-point or spiking neuron model. Then a simple simulated solution of the first passage time problem of the birth and death process applied in this model was discussed. In case of olfactory cells, the model exhibited a behaviour similar to the experimental data with parameter values corresponding to the suprathreshold concentrations of an odorant. PMID- 7797046 TI - Interpretation of the inotropic effect of 2,3-butanedione monoxime on the isometric twitch of guinea-pig papillary muscle. AB - The negative inotropic effect of 2,3-butanedione monoxime (BDM) on the isometric twitch of guinea-pig papillary muscle was analysed by parameters characterizing the time course of the mechanogram. BDM at concentrations of up to 4 mmol/l produced a clear negative inotropic effect, whereas the Ca transient measured in isolated cardiomyocytes was only slightly affected. Peak force was more reduced than dF/dtmax and dF/dtmin. This led to an earlier, more narrow peak and a shortening of twitch duration. Based on a reaction scheme for the cross-bridge cycle, a mathematical model using a Ca transient and mechanograms as input data has been developed. The kinetic parameters were estimated by fitting the model to various time courses of force obtained at rising concentrations of BDM. BDM decreased the ratio of rate constants for cross-bridge attachment and detachment in a concentration-dependent manner: the formation of cross-bridges became inhibited, whereas dissociation was promoted. Above 4 mmol/l BDM the more marked alterations of the parameters of the mechanogram indicated an additional suppressing effect on intracellular Ca supply. The computer analysis suggests how the cellular mechanism(s) of the BDM-induced negative inotropic effect are reflected in the time course of the mechanogram. PMID- 7797047 TI - The effect of albumin on incorporation of merocyanine 540 into phospholipid liposomes. AB - Absorption and fluorescence emission spectroscopy was applied to study the changes in albumin modified incorporation of merocyanine 540 into liposomes composed of different lecithins (DMPC, DPPC, POPC, and egg PC). Our results confirmed high affinity of merocyanine molecules toward albumin and revealed that albumin competed with all phospholipids used for binding merocyanine 540 molecules. However, the extent of this competition was determined by the kind of phospholipid. Albumin competed very successfully with lecithins containing saturated fatty acid chains (DPPC, DMPC) and weakly with unsaturated lecithins (POPC, egg PC) for binding merocyanine 540 molecules. PMID- 7797048 TI - Enzyme kinetics and the activation energy of (Na,K)-ATPase in ischaemic hearts: influence of the duration of ischaemia. AB - Hearts from male rats were incubated at 37 degrees C for variable periods of global ischaemia. Estimation of kinetic parameters of (Na,K)-ATPase at 37 degrees C in the presence of increasing concentrations of ATP revealed a significant decrease of Vmax in the first 15 minutes of ischaemia with further stabilization at the lowest level in 45-60 minutes of ischaemia. The changes in ATP binding site occurred later after 45 minutes of ischaemia as showed by the decrease of the Km value. As to the activation energy, there were no significant differences between control and ischaemic hearts. PMID- 7797049 TI - Influence of salmon melanin concentrating hormone on vasopressin analogue (dDAVP) activity and sodium transport in frog skin. AB - Salmon melanin-concentrating hormone (sMCH) is a peptide known to regulate skin pigmentation both in fish and tetrapod (frog and lizard). To evaluate the influence of sMCH on ionic transport in frog skin, standard voltage-clamp technique for the measurement of transepithelial short-circuit current (ISC) reflecting net sodium transport was used. It was found that sMCH alone applied at concentrations of 0.5; 5 or 10 mumol/l failed to influence ISC. The application of 5 mumol/l of sMCH, however, inhibited ISC across the skin stimulated by a synthetic analogue of vasopressin (dDAVP), whereas no influence on natriferic effect of 1 mumol/l forskolin by the studied peptide was observed. The results indicate that cAMP was presumably not involved in the mediation of sMCH action in frog skin. We assume that the interaction of sMCH with the basolateral membrane could lead either (1) to changes of membrane structure including organization of its lipid surrounding or (2) to modification of AVP/dDAVP receptor activity and binding capacity. The nature of these interactions and change(s) in cell membrane and signal(s) which trigger processes responsible for the inhibitory effect of sMCH on dDAVP-stimulated frog skin sodium transport remains to be elucidated. PMID- 7797050 TI - Inhibition of fructose diphosphate aldolase by phosphatidylserine liposomes. PMID- 7797051 TI - Inhibition of (Na/K)-ATPase by NFE induces an increase in mechanical activity of perfused guinea-pig heart. AB - The effect of 1-(5-nitro-2-furyl)-2-(phenylsulfonyl)-2-(furylcarbonyl)- ethylene (NFE) on stimulation of (Na/K)-ATPase by sodium and potassium ions was tested in isolated, partially purified sarcolemmal preparation from guinea-pig hearts. NFE inhibited competitively the stimulation of the enzyme by increasing concentrations of potassium. This inhibition was characterized by a significant (p < 0.001) increase of the K0.5 value, a considerable decrease of the Hill's cooperativity constant n as well as by an insignificant diminution of the Vmax value. Contrary to the effect on stimulation by potassium, NFE inhibited non competitively the stimulation of the ATPase by sodium ions with a significant (p < 0.001) depression of Vmax but without any considerable effect on the K0.5 and n values. These results indicated that NFE may interact with the molecule of (Na/K) ATPase in a locus close to or identical with the potassium binding site of the enzyme, i.e., in a similar mode as it was well documented for ouabain. This possibility was strongly supported by the finding that NFE administered at the concentration of 0.1 mumol/l in the perfusion medium increased significantly (p < 0.01) the mechanical activity of isolated perfused guinea-pig heart (Langendorff preparation). Nevertheless, it also caused some adverse effects such as a slight increase in coronary flow resistance and in heart rate as well as in the left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797052 TI - Na(+)-Ca++ exchange mechanism in smooth muscle of the ureter. AB - The participation of Na+ in regulation of intracellular Ca++ content and in formation of spontaneous action potentials of guinea-pig ureter was studied. It was shown that the fast decrease of intracellular Ca++ in the Ca(++)-loaded muscles was accompanied by enhancement of Na+ content in the cells. The concentration gradient of Na+ was found to define the effectiveness of Ca(++) extrusion from Ca(++)-loaded cells. The decrease of intracellular Ca++ showed a sigmoidal dependence on Na+ content in the medium. A correlation was established between the concentration gradient of Na+ and the formation of action potential plateau of ureter smooth muscle cells. The duration of action potential plateau decreased in accordance with Ca++ efflux and Na+ influx. The results confirmed the participation of Na(+)-Ca++ exchange mechanism in support of Ca++ cellular homeostasis as well as in the generation of action potentials of guinea-pig ureter. PMID- 7797053 TI - Effect of metabolic inhibitors on K+ transport across the lamprey (Lampetra fluviatilis) erythrocyte membrane. AB - In order to assess the contribution of oxidative metabolism to K+(86Rb+) transport across the lamprey red cell membrane, the effects of various metabolic inhibitors were examined. The influx of K+ was reduced markedly in the presence of 20 mumol/l 2,4-dinitrophenol (2,4-DNP) or rotenone, and to a lesser extent by 1 mmol/l cyanide. Rotenone produced complete inhibition of the K+ active transport and a partial blockade of K+ channels by 28% on the average. Addition of 2,4-DNP to incubation media resulted in a significant reduction of both active transport of K+ (by 47%) and of K+ movement via channels (by 57%). The inhibitory effect of 2,4-DNP on total K+ influx was independent on decreasing extracellular pHe from 7.4 to 6.5. The blocking action of 1 mmol/l Ba2+ on K+ channels was abolished in the red cells incubated at pHe 6.5. Treatment of the red cells with 1 mmol/l cyanide diminished active transport of K+ to about 34% of control values but did not affect K+ channels. The obtained data indicate that in the lamprey red blood cells at least a half of energy needed for the active transport of K+ is supplied with ATP produced by oxidative phosphorylation. It may be suggested that NADH dehydrogenase is the key enzyme required for active transport of K+ in the cells, as rotenone, a selective blocker of this enzyme, causes a complete blockade of the Na+, K(+)-pump. PMID- 7797054 TI - Immobilization stress enhances lipid peroxidation in the rat lungs. Materials and methods. AB - The present work was carried out to study the involvement of lipid peroxidation in immobilization-induced damage of the rat lung. Thirty-hour immobilization stress was found to result in a marked morphological alteration of the lung ultrastructure and in significant increases of both acid and alkaline phosphatase for immobilization times exceeding 12 and 24 hours respectively. Also, increased concentrations of conjugated dienes and fluorescent products of lipid peroxidation were measured in the lungs of rats immobilized over 12 h. Immobilization stress was followed by significant changes in the fatty acid contents of lung phospholipids. The levels of polyunsaturated fatty acids C-18:2 (linoleic acid) and C-20:4 (arachidonic acid) were decreased even during the alarm phase. The contents of monounsaturated fatty acids did not change, while those of saturated fatty acids slightly increased. The involvement of lipid peroxidation in immobilization-induced damage of the rat lung was indirectly supported by the observation of decreased levels of vitamin E at 12 h immobilization. All the above data suggest that lipid peroxidation is somehow involved in the immobilization-induced damage of the rat lung. The observed changes in lipid peroxidation preceded the immobilization stress-induced damage of the lung cell membranes. Therefore, it seems likely that lipid peroxidation is the cause, rather than a consequence of the stress-altered lung structure. PMID- 7797056 TI - Can a single bacteriorhodopsin molecule change the structural state of one liposome? AB - Using ultrasonic velocity measurements the interaction of bacteriorhodopsin (BR) with large unilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) was studied in gel (25 degrees C) and in liquid crystalline state (50 degrees C) of lipid bilayer. We could show that with the increasing BR concentration the increment of ultrasonic velocity increases and a saturation occur at a BR/Liposomes of ratio approximately 0.5 mol/mol. BR incorporation into the lipid bilayer in gel state leads to an increase of the increment of the ultrasonic velocity of the lipid to 9.51 +/- 1.47 ml/mol. This could be mainly attributed to a decrease in membrane compressibility or an increase in membrane volume or both. No changes of ultrasonic velocity increment were observed with the membrane in liquid crystalline state. In this case, BR probably is not able to change the mechanical properties of a considerably disordered membrane. PMID- 7797055 TI - Effects of Cu(II) complexes on photosynthesis in spinach chloroplasts. Aqua(aryloxyacetato)copper(II) complexes. AB - The inhibitory effect of 14 aqua(aryloxyacetato) copper(II) complexes on oxygen evolution rate in spinach chloroplasts has been investigated. The inhibitory effect of these effectors on photosynthesis was confirmed by Hill reaction as well as by EPR and fluorescence spectroscopies. The results of the EPR study showed that the sites of action of the studied effectors are Z+ and Y+ intermediates at the donor side of the photosystem (PS) 2. The EPR study also showed that another site of action is the oxygen evolving complex, namely its manganese cluster. The above suggestions were supported by the results of the fluorescence study as well. Based on the restoring of the photosynthetic electron transport to 2,6-dichlorophenol-indophenol in chloroplasts inhibited by the studied Cu(II) complexes using sym-diphenylcarbazide it can be assumed that the own core of PS2 (P680) and a part of the electron transport chain-at least up to plastoquinone-remain intact. PMID- 7797057 TI - Stochastic description of protein conformational motion. AB - Green function analysis of the Fokker-Planck equation was used to describe protein conformational motion for approximate variational derivation of typical rate constant of protein relaxation from excited nonequilibrium state to the equilibrium. This approach was illustrated on a simple one-dimensional conformational potential. PMID- 7797058 TI - Mediator assays and modulation of inflammation in asthma: introduction. AB - The vital role of inflammation in the induction and perpetuation of asthmatic responses is now a widely accepted concept. Effective management of asthma requires modulation of asthmatic inflammatory responses. Eosinophils play a critical role in producing inflammation within the asthmatic lungs. Serologic assessment of the level of eosinophilic cationic protein (ECP) may be useful in assessing the degree of activation of eosinophils in asthma and the effect of pharmacotherapy on activated eosinophils. Several clinical trials have noted that ECP levels fluctuate in direct relationship to the amount of ongoing bronchospasm and asthmatic inflammation. Modulation of inflammation in asthma can occur through pharmacologic means. Nedocromil sodium has been demonstrated to significantly affect both early-phase and late-phase inflammatory events including effects on mast cell activation and effects on eosinophil function. Nedocromil sodium has also been noted to affect production and activity of cytokines that are vital to the perpetuation of the asthmatic late-phase response. Unlike cromolyn sodium, nedocromil sodium inhibits late-phase inflammation even when administered after the early phase of the allergic response and has also been demonstrated to be a steroid-sparing agent in mild-to moderate asthmatics who require inhaled beclomethasone. Modulation of the metabolism of arachidonic acid, thereby affecting levels of prostaglandins and leukotrienes, may be extremely useful in selective asthmatic patients. Those patients having aspirin sensitivity and chronic rhinitis associated with asthma seem to be particularly responsive to arachidonic acid metabolites. In such patients, use of aspirin desensitization may be considered. Newer anti inflammatory agents being investigated as treatments for asthma include methotrexate, hydroxychloroquin, auronifin, and sulfonylureas, among others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797059 TI - Clinical application of eosinophilic cationic protein in asthma. AB - Among the inflammatory cells involved in the pathogenesis of asthma, eosinophils have been recognized as highly significant participants in the late-phase of the inflammatory response. Bronchial challenge with allergen inducing inflammation and exacerbation of asthma results in activation of eosinophils and release of specific eosinophil mediators, including eosinophil cationic protein (ECP). Recent studies have demonstrated that activation of eosinophils and increase of their release of ECP occur in patients naturally exposed to allergen, and in patients having inflammatory exacerbations of asthma, including development of bronchial hyperreactivity. ECP is elevated during exacerbation of extrinsic and intrinsic asthma in direct relationship to concomitant decrease in pulmonary function and increasing asthma symptoms. The elevated serum levels of ECP decline subsequent to effective therapy. Monitoring modulation of ECP levels may be useful in evaluating the treatment of asthmatic patients and as a marker for the efficacy of therapy. Several investigations have strongly suggested that serial determination of ECP in asthmatics may be especially useful as an inflammatory correlate to the mechanical abnormalities assessed by determination of pulmonary function in asthmatic patients. PMID- 7797060 TI - Inhaled corticosteroid treatment for asthma. AB - Increased numbers of goblet cells associated with decrease in the ciliated epithelium occur at an early stage in the patient with asthma. Recent bronchial biopsy studies have demonstrated that these changes may occur even in the mildest asthmatic patient. The protective function of the epithelium is thus compromised and secretion enhanced in early asthma. Anti-inflammatory therapy should be employed at an early stage in the asthmatic patient. Avoidance of allergen is also essential if the source of the inflammation is atopic disease. Inhaled corticosteroids not only reduce bronchial hyperresponsitivity, but also improve the diurnal variation that occurs in lung function in the asthmatic patient. Inhaled corticosteroid therapy is associated with the normalization of the ciliated to goblet cell ratio and a reduction in the inflammatory cell infiltrate, including most notably a reduction in eosinophil within the lamina propria and respiratory epithelium. These changes induced by inhaled corticosteroids are not noted when inhaled beta 2-agonists are employed alone as therapy for asthma. The use of inhaled corticosteroids may thus potentially reverse the pathologic changes that occur even in the early asthmatic patient, whereas utilization of inhaled beta 2-agonists failed to improve histologic abnormalities that occur in early asthma. PMID- 7797061 TI - Immunopharmacologic profile of nedocromil sodium. AB - Nedocromil sodium, a pyranoquinolone, was specifically designed as an agent to suppress allergic inflammation. Nedocromil sodium significantly affects not only the early-phase of allergen-induced responses, but also expression of late-phase inflammation, even when administered after the onset of early-phase responses. Nedocromil sodium also limits bronchoconstriction induced by nonallergic factors, including cold air and sulfur dioxide at dosages lower than required with cromolyn sodium. Nedocromil sodium is more potent than cromolyn sodium in preventing mast cell degranulation in selective animal models. In addition, nedocromil sodium limits leukotriene C4 production by calcium ionophore stimulated eosinophils and also limits the activity of platelet activating factor to induce neutrophil generation of superoxides. Diurnal variation of peak flow rates in asthmatics and requirement for both beta 2-agonists and inhaled beclomethasone have been noted to be reduced in several trials employing nedocromil sodium, suggesting that its in vivo activity parallels its in vitro activity as an anti-inflammatory agent. PMID- 7797062 TI - Clinical overview of nedocromil sodium. AB - Nedocromil sodium is a novel anti-inflammatory agent that has been demonstrated to significantly improve pulmonary function and decrease bronchial hyperreactivity in asthmatic patients. Currently available only as an inhaled drug, nedocromil sodium has an excellent safety profile, the only adverse effect being a slightly unpleasant taste. Nedocromil sodium has been used as a replacement for sustained-release theophylline therapy; the overall efficacy of nedocromil sodium is at least equivalent to that of theophylline, with less adverse effects occurring in those patients treated with nedocromil sodium rather than with theophylline. Nedocromil sodium also appears to be equal in efficacy to low doses of beclomethasone when employed in patients with mild to moderate asthma. Addition of nedocromil sodium to an ongoing regimen of beclomethasone may also allow for reduction in the dosage of inhaled corticosteroid. The overall safety of therapy with nedocromil sodium suggests that it be considered as initial therapy for those patients having mild to moderate asthma. PMID- 7797063 TI - Aspirin sensitive rhinosinusitis and asthma. AB - Although aspirin sensitive asthma has been recognized as a clinical entity since the beginning of this century, the mechanism for the production of this syndrome still remains obscure. Recent studies have indicated a higher than previously appreciated incidence of aspirin sensitive asthma, perhaps approaching 40% of steroid-dependent asthmatics. Challenge with both oral and bronchial instilled aspirin may be useful to identify aspirin-sensitive individuals. During aspirin induced reactions, increased vascular permeability is noted. In addition, aspirin sensitive individuals have altered levels of production of leukotriene E4 and enhanced sensitivity to inhaled leukotriene E4. However, nasal secretions of aspirin-sensitive individuals demonstrate enhanced leukotriene C4 concentration after aspirin challenge. It has also been noted that nonaspirin-sensitive patients have enhanced leukotriene C4 concentration. Thus, the specific defect leading to the pathogenesis of aspirin-sensitive asthma and rhinosinusitis in selected individuals remains obscure. Eosinophil activation has been noted in aspirin-sensitive rhinosinusitis patients; however, other cell types, including platelets and monocytes, have also been noted to exhibit metabolic abnormalities in this syndrome. Aspirin desensitization may be a useful option in selected patients with significant aspirin sensitive rhinosinusitis and asthma. PMID- 7797064 TI - Immunosuppressive therapy for asthma. AB - Over the last four or five years, there have been some serious attempts to look for alternatives to corticosteroids in the management of severe bronchial asthma. Rheumatologists and dermatologists long ago recognized the importance of replacing corticosteroids with other agents. Some agents such as methotrexate are now clearly established through multiple double-blind trials as being appropriate substitutes for corticosteroids, whereas other agents which have been investigated, such as cyclosporin, are very promising. Finally, a third group of agents, including troleandomycin (TAO), have been found to be totally inappropriate as possible substitutes for corticosteroids. PMID- 7797065 TI - Stevens-Johnson syndrome presenting as intravenous line sepsis. AB - A 25-year-old Hispanic female with insulin dependent diabetes mellitus (IDDM) and endstage renal disease on chronic hemodialysis was hospitalized with paroxysms of fever and chills for a day. A day after starting piperacillin for presumed intravascular line infection, she developed a maculopapular dermatitis and abnormal liver function tests, at which point the drug was discontinued. However, the rash persisted for 10 days, after which it progressively worsened. She continued to have high fevers, abnormal liver function tests, and marked leukocytosis, despite multiple negative cultures and other nondiagnostic examinations. She was treated as a patient with sepsis of unknown etiology and received multiple antibiotics on an empiric basis without response. A diagnosis of Stevens-Johnson syndrome was then made based on the triad of cutaneous dermatitis, mucosal, and hepatic involvement. She received high dose corticosteroids and her fever, dermatitis, mucosal lesions, leukocytosis, and abnormal liver function tests improved dramatically. PMID- 7797067 TI - Detection of airborne natural rubber latex by immunoelectrophoresis, RAST inhibition, and immunospot method. AB - Occupational dermal and respiratory allergies caused by natural rubber latex (NRL) have been encountered with increasing frequency in health care workers. In order to measure the amount of airborne NRL, area and personal air sampling was performed in three hospital laboratories where workers used latex gloves. The total dust levels in laboratory air samples were lower than 0.17 mg/m3. RAST inhibition suggested that NRL antigens may exist both in the area and personal samples. Immunospot measurements, rocket immunoelectroporesis, and rocket radioimmunoelectrophoresis did not show any NRL activities in laboratory airsamples, although they were able to detect immunoactive material in positive control filter specimens. We conclude that the airborne NRL concentration was undetectable in daily hospital laboratory environment where workers used disposable NRL gloves. Airborne NRL, however, can be measured by using immunological assays. PMID- 7797069 TI - Oncogenes: 20 years later. PMID- 7797066 TI - Sensitization to inhalant allergens in children diagnosed with food hypersensitivity. AB - In order to characterize the profile of inhalant allergen sensitizations in patients with food hypersensitivity, we carried out a screening process using a standard panel of inhalant allergens by SPT. We screened 437 patients (mean age 5.4 years, 4.1 SD) who showed anti-allergen IgE to one or several foods, determined by both SPT and RAST. In each case in which a positive SPT to inhalant appeared, a new individualized search for these allergens was performed by both SPT and Phadezym RAST. We found sensitization to aeroallergens in 272 of the 437 children (62%) with sensitization to foods (52% of all patients were sensitized to pollens, 17% to dermatophagoides, and 26% to animal allergens). The number with sensitization to aeroallergens was proportionally increased in relation to the number of food sensitizations (p < 0.05). Sensitization to pollen allergen were found with higher frequency (p < 0.001) in patients with sensitization to fruits, legumes, and other vegetables (mainly walnuts, chestnuts, melons, or sunflower seeds) than in those sensitive to foods of animal origin. Sensitization to dermatophagoides and animal allergens did not show any special distribution relative to the kind of food sensitization. Seventeen patients with sensitization to egg showed sensitization to avian feathers. This type of sensitization did not appear in the remainder of patients evaluated. PMID- 7797068 TI - Commentary: rename our field allergy, asthma, and clinical immunology. PMID- 7797070 TI - Thinking about Howard Temin. PMID- 7797071 TI - Cancer: the rise of the genetic paradigm. PMID- 7797072 TI - A conjugation-like mechanism for prespore chromosome partitioning during sporulation in Bacillus subtilis. AB - Spore formation in Bacillus subtilis begins with an asymmetric cell division that superficially resembles the division of vegetative cells. Mutations in the spoIIIE gene of B. subtilis partially block partitioning of one chromosome into the smaller (prespore) compartment of the sporulating cell. Point mutations that specifically block prespore chromosome partitioning affect a carboxy-terminal domain of SpoIIIE that shows significant sequence similarity to the DNA transfer (Tra) proteins of several conjugative plasmids of Streptomyces. In wild-type sporulating cells, the prespore chromosome passes through an intermediate stage resembling the state in which spoIIIE mutant cells are blocked. The prespore chromosome is then transferred progressively through the newly formed spore septum. We propose that translocation of the prespore chromosome occurs by a mechanism that is functionally related to the conjugative transfer of plasmid DNA. PMID- 7797073 TI - Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. AB - Drosophila cyclin E (DmcycE) is required in embryos for S phase of mitotic and endoreduplication cycles. Here, we describe regulatory differences characteristic for these two cell cycle types. While DmcycE transcript levels decline in DmcycE mutant cells programmed for mitotic proliferation, they are maintained and no longer restricted to transient pulses in DmcycE mutant cells programmed for endoreduplication. Moreover, DmcycE expression in endoreduplicating cells is down regulated by ectopic expression of a heat-inducible cyclin E transgene. DmcycE expression in endoreduplicating tissues, therefore, is restricted by a negative feedback to the transient pulse triggering entry into S-phase. Conversely, during mitotic cycles, where S phase entry is not only dependent on cyclin E but also on progression through M phase, cyclin E and associated Dmcdc2c kinase activity are present throughout the cell cycle. Reinitiation of DNA replication during the G2 phase of the mitotic cell cycle, therefore, is prevented by cyclin E/Dmcdc2c kinase-independent regulation. Observations in cyclin A mutants implicate G2 cyclins in this regulation. Our results suggest molecular explanations for the different rules governing S phase during mitotic and endoreduplication cycles. PMID- 7797074 TI - Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. AB - The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes. These kinases phosphorylate a number of cellular substrates, among which is the product of the retinoblastoma gene, pRb. Phosphorylation of pRb in late G1 causes the release of the transcription factor E2F from pRb, resulting in the transcriptional activation of E2F-responsive genes. We show here that phosphorylation of the pRb-related p107 is also cell cycle regulated. p107 is first phosphorylated at 8 hr following serum stimulation of quiescent fibroblasts, which coincides with an increase in cyclin D1 protein levels. Consistent with this, we show that a cyclin D1/cdk4 complex, but not a cyclin E/cdk2 complex, can phosphorylate p107 in vivo. Furthermore, phosphorylation of p107 can be abolished by the overexpression of a dominant-negative form of cdk4. Phosphorylation of p107 results in the loss of the ability to associate with E2F 4, a transcription factor with growth-promoting and oncogenic activity. A p107 induced cell cycle block can be released by cyclin D1/cdk4 but not by cyclin E/cdk2. These data indicate that the activity of p107 is regulated by phosphorylation through D-type cyclins. PMID- 7797075 TI - Activation of the TFIID-TFIIA complex with HMG-2. AB - The nonhistone chromosomal protein HMG-2 was identified as a factor necessary for activation in a defined transcription reaction in vitro containing RNA polymerase II and purified factors. Activation occurred on all promoters assayed except that of the immunoglobulin IgH gene. TFIIA was required for stimulated levels of transcription. The activation process depended on the presence of TAFs in the TFIID complex and generated a preinitiation complex from which TFIIB dissociated more slowly. However, titration of TFIIB over three orders of magnitude did not obviate the requirement of activator and HMG-2 to achieve stimulated levels of transcription. Analysis of the activated reaction identified the TFIID-TFIIA complex as the first stage of modification during activation. These results suggest that activation can occur solely in the presence of the basal factors, activator protein, and an "architectural" HMG factor, which probably stabilizes an activated conformation of the TFIID-TFIIA-promoter complex. PMID- 7797076 TI - Dissection of progesterone receptor-mediated chromatin remodeling and transcriptional activation in vivo. AB - We have investigated whether constitutive binding by the progesterone receptor (PR) to a promoter is required for the maintenance of an open chromatin structure in vivo. For these experiments, we used human T47D breast cancer cells in which the mouse mammary tumor virus (MMTV) promoter, stably assembled as chromatin, is constitutively hypersensitive to endonucleolytic cleavage. In vivo footprinting revealed that transcription factors nuclear factor 1 and the PR were constitutively bound to the MMTV promoter in these cells. Treatment of these cells for 1 hr with the steroid antagonist ZK98299 prevented PR binding to chromatin in vivo and reversed hypersensitivity, leading to the loss of transcription factor binding. The reduction in hypersensitivity induced by ZK98299 was readily reversed by treatment with the progestin R5020. The chromatin organization of the promoter could be cycled between the open and closed states by consecutive treatments with agonist or antagonist. The antagonist RU486 also blocked activation of transcription and the assembly of a transcription preinitiation complex, but in contrast to ZK98299, maintained the hypersensitive chromatin state. Taken together, these results suggest that PR binding to chromatin is sufficient to induce hypersensitivity to endonucleolytic cleavage. Furthermore, they indicate that the PR binding to DNA and the resulting chromatin hypersensitivity is functionally separate from transcriptional activation in vivo. PMID- 7797077 TI - Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator. AB - The immunoglobulin light-chain gene enhancers E kappa 3', E lambda 2-4, and E lambda 3-1 contain a conserved cell type-specific composite element essential for their activities. This element binds a B cell-specific heterodimeric protein complex that consists of the Ets family member PU.1 and a second factor (NF-EM5), whose participation in the formation of the complex is dependent on the presence of DNA-bound PU.1. In this report we describe the cloning and characterization of Pip (PU.1 interaction partner), a lymphoid-specific protein that is most likely NF-EM5. As expected, the Pip protein binds the composite element only in the presence of PU.1; furthermore, the formation of this ternary complex is critically dependent on phosphorylation of PU.1 at serine-148. The Pip gene is expressed specifically in lymphoid tissues in both B- and T-cell lines. When coexpressed in NIH-3T3 cells, Pip and PU.1 function as mutually dependent transcription activators of the composite element. The amino-terminal DNA-binding domain of Pip exhibits a high degree of homology to the DNA-binding domains of members of the interferon regulatory factor (IRF) family, which includes IRF-1, IRF-2, ICSBP, and ISGF3 gamma. PMID- 7797078 TI - Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies. AB - The myogenic basic helix-loop-helix (bHLH) proteins MyoD, myf5, myogenin, and MRF4 can initiate myogenesis when expressed in nonmuscle cells. During embryogenesis, each of the myogenic bHLH genes is expressed in a unique temporospatial pattern within the skeletal muscle lineage, suggesting that they play distinct roles in muscle development. Gene targeting has shown that MyoD and myf5 play partially redundant roles in the genesis of myoblasts, whereas myogenin is required for terminal differentiation. MRF4 is expressed transiently in the somite myotome during embryogenesis and then becomes up-regulated during late fetal development to eventually become the predominant myogenic bHLH factor expressed in adult skeletal muscle. On the basis of its expression pattern, it has been proposed that MRF4 may regulate skeletal muscle maturation and aspects of adult myogenesis. To determine the function of MRF4, we generated mice carrying a homozygous germ-line mutation in the MRF4 gene. These mice showed only a subtle reduction in expression of a subset of muscle-specific genes but showed a dramatic increase in expression of myogenin, suggesting that it may compensate for the absence of MRF4 and demonstrating that MRF4 is required for the down regulation of myogenin expression that normally occurs in postnatal skeletal muscle. Paradoxically, MRF4-null mice exhibited multiple rib anomalies, including extensive bifurcations, fusions, and supernumerary processes. These results demonstrate an unanticipated regulatory relationship between myogenin and MRF4 and suggest that MRF4 influences rib outgrowth through an indirect mechanism. PMID- 7797079 TI - Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA. AB - Transient transfection of the U1 snRNP 70K protein into COS cells induced nuclear reorganization and redistribution of the splicing factor SC-35, whereas hnRNP proteins were not affected. Correspondingly, splicing and nucleocytoplasmic transport of a coexpressed mRNA substrate was reduced by overexpression of U1 70K. The carboxy-terminal portion of U1-70K-encompassing repeats of Arg/Ser, Arg/Glu, and Arg/Asp localizes to the nucleus independently of U1 RNA and was responsible for these inhibitory effects. This region of U1-70K contains amino acid residues similar to those found in splicing factors SC-35, U2AF, su(wa), and in other SR proteins suggesting that U1-70K protein may serve as a focus of assembly for functional components of the splicing/transport machinery. These findings are compatible with models that propose that direct interaction between U1-70K and SR proteins play a regulatory role in early events of spliceosome assembly. PMID- 7797080 TI - Exonucleolytic processing of small nucleolar RNAs from pre-mRNA introns. AB - Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron encoded snoRNA, U19. Experiments in which the processing of intronic RNA substrates was tested in HeLa cell extracts suggest that exonucleases rather than endonucleases are involved in the excision of U17 and U19 RNAs: (1) Cutoff products that would be expected from endonucleolytic cleavages were not detected; (2) capping or circularization of substrates inhibited formation of snoRNAs; and (3) U17 RNA was faithfully processed from a substrate carrying unrelated flanking sequences. To study in vivo processing the coding regions of snoRNAs were inserted into intron 2 of the human beta-globin gene. Expression of resulting pre mRNAs in simian COS cells resulted in formation of correctly processed snoRNAs and of the spliced globin mRNA, demonstrating that snoRNAs can be excised from a nonhost intron and that their sequences contain all the signals essential for accurate processing. When the U17 sequence was placed in a beta-globin exon, no formation of U17 RNA took place, and when two U17 RNA-coding regions were placed in a single intron, doublet U17 RNA molecules accumulated. The results support a model according to which 5'-->3' and 3'-->5' exonucleases are involved in maturation of U17 and U19 RNAs and that excised and debranched introns are the substrates of the processing reaction. PMID- 7797081 TI - The Hermann Wacker Prize Awarded to Prof. Franz Fankhauser, Switzerland. PMID- 7797082 TI - Galactose-containing glycoconjugates of the iris, the aqueous outflow passages and the cornea in capsular glaucoma. A lectin histochemical study. AB - BACKGROUND: The aim of the study was to compare galactose-containing glycoconjugates of the iris, the aqueous outflow passages and the cornea with exfoliation material in capsular glaucoma. METHODS: Six formalin-fixed, paraffin embedded human eyes with capsular glaucoma and six control eyes were studied by using a panel of 11 biotinylated lectins to galactose- and N-acetylgalactosamine containing glycoconjugates. RESULTS: The Gal (beta 1-->3) GalNAc-reactive lectins peanut agglutinin (PNA) and Bauhinia purpurea alba agglutinin (BPA) and the Gal (beta 1-->4)GlcNAc-reactive lectins Ricinus communis agglutinin (RCA-I) and Phaseolus vulgaris erythroagglutinin (PHA-E) gave the strongest label with exfoliation material. Lectin binding to the iris was variable. The binding of PNA, BPA, RCA-I, Erythrina cristagalli agglutinin (ECA), PHA-E and Glycine max agglutinin (SBA) to the subendothelial region of iris blood vessels closely resembled their binding to exfoliation material. RCA-I and PHA-E bound moderately to the aqueous outflow passages. The surface of the corneal epithelium showed positive reaction with most lectins studied, but the keratocytes reacted with RCA I and PHA-E only. Neuraminidase pretreatment generally increased the reaction intensity. CONCLUSIONS: The findings suggest that the glycoconjugate composition of exfoliation material in the classical locations along the anterior and posterior chamber closely resembles that in the subendothelial region of iris blood vessels. PMID- 7797083 TI - Optic disc morphology in diabetes mellitus. AB - BACKGROUND: Diabetes mellitus is a systemic disease affecting multiple tissues throughout the body. This study was performed to evaluate intravitally the diabetic changes of the optic disc. METHODS: Color photographs of 115 eyes with varying severity of diabetic retinopathy and of 29 normal eyes were morphometrically examined. RESULTS: We found that the size and shape of the optic disc, the neuroretinal rim and the parapapillary atrophy did not differ significantly between the diabetic eyes and the normal eyes. These variables were independent of the degree of diabetic retinopathy. There was a tendency toward decreased visibility of the retinal nerve fiber layer and increased optic disc pallor in the diabetic eyes. CONCLUSION: The results indicate that the area and form of the optic disc, the neuroretinal rim and parapapillary atrophy are not altered by diabetes mellitus. This is important for the diagnosis of glaucoma in diabetic patients, since glaucoma leads to a decrease of rim area and an enlargement of parapapillary atrophy. The reduced visibility of the retinal nerve fiber layer, the increased optic disc pallor and the unchanged size of the neuroretinal rim and parapapillary atrophy suggest that diabetes mellitus may be associated with nonglaucomatous optic nerve atrophy. PMID- 7797084 TI - Cryotherapy for eyelid and periocular basal cell carcinomas: outcome in 166 cases over an 8-year period. AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common of all malignant tumours and often appears on the periocular skin. In the present study, patients with 166 eyelid and periocular BCCs were treated with cryotherapy at the Eye Clinic of the Kuopio University Hospital. Seven patients with a total of eight BCCs died during the first year after cryotherapy, of causes unrelated to BCC. These cases were excluded from the analysis of outcome. METHOD: The tumours were photographed before excisional biopsy and histopathological examination. The BCCs were frozen twice with liquid nitrogen in a closed cryoprobe; a tissue thermometer was used. RESULTS: During the mean follow-up of 5 years for 158 BCCs, recurrences were observed in 12 cases (7.6%). The most important prognostic factors for recurrence were large tumour size (maximum diameter exceeding 10 mm), tumour extension into the lid margin, and cicatrising (morpheaform) BCC. The complications of cryotherapy were slight, but in some cases lid ectropion needed surgical correction. The functional and cosmetic results were very satisfactory in most cases. CONCLUSION: Ninety-two percent of BBCs treated with cryotherapy did not recur during mean follow-up of 5.0 years (range 1.6-8.4 years). PMID- 7797086 TI - beta-Galactosidase transgene expression in transplanted rabbit retinal pigment epithelial cells in vivo. AB - BACKGROUND: Intraocular transplantation of genetically modified cells that release a particular substance could have a major impact on the treatment of various ocular diseases. We studied the expression of the reporter gene beta galactosidase (lacZ) in transplanted retinal pigment epithelial (RPE) cells in vivo. METHODS: RPE cells from pigmented rabbits were transduced with the beta galactosidase gene in a retroviral vector. Cells were then assayed for gene expression and transplanted subretinally into the eyes of New Zealand White rabbits. RPE cells that were transduced with a similar vector without the beta galactosidase gene were used as controls. Rabbits were killed on days 1, 7, and 21 and the eyes processed for transmission electron microscopy RESULTS: Neomycin resistant rabbit RPE cells that showed beta-galactosidase activity were generated within 2-5 weeks. After transplantation, viable RPE cells that expressed the transgene and that phagocytosed rod outer segments were observed on days 1, 7, and 21 CONCLUSIONS: The results show that generation of genetically modified RPE cells is feasible and that the transplanted cells remain viable and continue to express the transgene in the subretinal space of the host animal for at least 21 days. Transplantation of such genetically modified RPE cells could provide a new tool for studying retinal diseases and, potentially, for correcting metabolic abnormalities in retinal degenerations and dystrophies. PMID- 7797087 TI - Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate. AB - BACKGROUND: Lesions resembling those of human retinopathy of prematurity can be provoked in newborn Wistar rats by exposure to an FiO2 of 80% for the first 5 days of life followed by 5 days recovery under room-air conditions. METHODS: We evaluated the effects of moderate hyperbarism (+60.75 kPa, i.e. 455 mmHg or 0.6 atm) and topical administration of 0.25% timolol maleate on oxygen-induced retinopathy (OIR) in this experimental model. RESULTS: OIR (including neovascularization in most cases) was observed in 100% of the retinas of normobaric oxygen-reared ratlings that did not receive timolol. OIR was less frequent in oxygen-reared ratlings treated with hyperbarism (60%) or timolol (65%). Hyperbaric oxygen supplementation combined with timolol treatment during both the hyperoxic and room-air phases reduced the incidence of OIR to 30%. There was no sign of vasoproliferation in any of the retinas from the latter three groups. CONCLUSIONS: The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery. PMID- 7797085 TI - Adhesion molecules in normal and pathological corneas. An immunohistochemical study using monoclonal antibodies. AB - BACKGROUND: Adhesion molecules are cell surface receptors that are probably important in various cell-cell and cell-extracellular matrix interactions of the cornea. METHOD: In this immunohistochemical light-microscopic study we analyzed the expression pattern of adhesion molecules in normal and pathological human corneas (cases of corneal inflammation and degenerative disorders). The analyzed molecules included the beta 1 integrin or VLA family VLA-1-6, the beta 2 integrins or leukocyte integrins LFA-1, Mac-1, and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectins ELAM-1 and GMP-140. RESULTS: Inflamed cornea (in contrast to normal cornea). On corneal epithelium, increased expression of the alpha 2 subunit of VLA-2 was detected and ICAM-1 was induced on the basal epithelial cells. On corneal stromal keratocytes, LFA-3 was induced and expression of the alpha subunits of VLA-1-6 and ICAM-1 was increased. On vascular endothelium, VCAM-1 and ELAM-1 were induced and ICAM-1 and GMP-140 expression was increased. On corneal endothelium, ELAM-1 was induced and increased levels of the alpha 1 subunit of VLA-1 and GMP-140 were expressed. Degenerative disorders (in contrast to normal cornea): In corneas with degenerative disorders we found decreased expression of adhesion molecules. CONCLUSION: Inflammatory cytokines increase the expression of the adhesion molecules. Increased expression of the VLAs probably promotes cell-extracellular matrix and cell-cell interactions. ICAM 1, VCAM-1, LFA-3, ELAM-1 and GMP-140 expression was increased on vascular endothelium in inflamed corneas. Corresponding receptors on leukocytes probably enable a selective recruitment of different leukocyte populations in inflammatory corneal diseases. The decreased expression of adhesion molecules in corneal degenerative disorders is probably a sign of reduced cell-cell and cell extracellular matrix interactions. PMID- 7797088 TI - Release of lysosomal protease from retinal pigment epithelium and fibroblasts during mechanical stresses. AB - BACKGROUND: Mechanical expansion in tissues or in cells may occur under physiological and pathological conditions and is accompanied by increased activity of proteolytic enzymes. In traction detachment, retinal cells are subjected to mechanical strain. The purpose of this study was to ascertain whether retinal pigment epithelium (RPE) cells and fibroblasts in tissue culture release proteases due to mechanical stress and to investigate the importance of the cytoskeleton for mechanotransduction to the lysosomes during cellular stress reactions. METHODS: Cell layers were grown on silicone-rubber membranes and subjected to mechanical stresses by expansion of the membrane. Concentrations of N-acetyl-beta-glucosaminidase (NAG), acid phosphatase (AP), and lactate dehydrogenase (LDH) were determined in extracellular fluid. Colchicine 0.5 x 10( 5) M was used to disrupt the cytoskeleton prior to expansion. RESULTS: RPE cells and fibroblasts separated during mechanical expansion, which was accompanied by extracellular release of proteolytic activity of NAG (RPE 37.50%; fibroblasts 23.22% above control value), but not of AP. LDH activity did not increase, indicating preserved integrity of the cell membranes during stretching. Colchicine caused immediate detachment of fibroblasts, and RPE did not release significant activity of NAG under subsequent extension. CONCLUSION: In traction detachment, RPE may release in vivo proteases to cut intercellular adhesions in order to escape mechanical strain. Our results indicate that release of proteases from RPE may be involved in the pathophysiology of traction detachment, facilitating by their degradative action the disconnection between RPE and outer segments. Similarly, fibroblasts may respond to changes in tension of scleral or corneal tissue. Release of proteases following mechanical stress seems to require an intact cytoskeleton. PMID- 7797089 TI - Macular capillary particle velocities: a blue field and scanning laser comparison. AB - BACKGROUND: Two different techniques are available for measurement of macular capillary particle velocities. The psychophysical blue field simulation technique gives data on macular leukocyte flow velocities, while the scanning laser technique provides information on capillary blood velocities of hypofluorescent segments in the macular network. Published velocity data differ considerably between the two methods. The current study was undertaken to compare the two measuring techniques in a group of healthy volunteers. METHODS: Thirty-two healthy subjects (12 man, 20 women, mean age 27 years) participated in this study. All subjects underwent entoptic leukocyte visualization by means of blue field simulation followed by fluorescein angiography using scanning laser ophthalmoscopy. RESULTS: The capillary blood velocities measured using the scanning laser technique were significantly higher (P < 0.01) than the flow velocities estimated with the blue field simulation technique (2.68 +/- 0.3 mm/s vs 0.89 +/- 0.2 mm/s). No significant correlation between the flow velocities was found (r = -0.22). CONCLUSION: The differences may be related to different measuring locations and/or measurements of different phenomena. The blue field technique estimates average leukocyte flow in the macular network, whereas the scanning laser technique quantifies the velocity of erythrocyte aggregates in the capillary lumen of the para- and perifoveal network. A combination of both techniques may be helpful in interpreting physiological responsiveness and altered velocity pattern in diseased eyes. PMID- 7797090 TI - The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. AB - Oxidative stress and protein glycation are closely related processes that may contribute to the development of complications in diabetes mellitus. Treatment with antioxidants could protect against these processes at a biochemical level, and we have therefore investigated the effects of ascorbate and desferrioxamine treatment in the streptozotocin diabetic rat. Diabetic animals were given ascorbate 1 g/l in drinking water or desferrioxamine 6 mg/kg/day by subcutaneous injection and were killed after 6 weeks. In diabetic animals, oxidative stress was increased as shown by increased levels of conjugated dienes (CD) in plasma and malondialdehyde (MDA) in plasma, erythrocyte membranes, and urine. In addition, there was depletion of the nutritional antioxidants ascorbate, alpha tocopherol, and retinol. Insulin treatment returned all of these parameters to normal. Ascorbate supplementation or desferrioxamine treatment alone failed to reduce oxidative stress, but a combination of both interventions restored MDA, CD, and antioxidant vitamins to control values. Both ascorbate and desferrioxamine also reduced HbA1c and glycated albumin levels. Treatment with antioxidants can reduce both oxidative stress and protein glycation and may help to reduce the risk of developing diabetic complications. However, ascorbate can have both prooxidant and antioxidant effects in vivo, and its use in pharmacological doses should be approached with caution. PMID- 7797091 TI - Radical mechanisms of cephalosporins: a pulse radiolysis study. AB - Radiosterilization induces radicals, and it is very important to describe radical mechanisms before the possible use of cephalosporins gamma sterilization. Moreover, physiological or radiotherapeutically induced free radicals also initiate radical mechanisms. For this study, pulse radiolysis was used. This method permits to avoid in vivo direct study difficulties of bioradical processes and gives quantitative data. Reactions of solvated electron (eaq-), hydroxyl radical (.OH), azide radical (N3.), dibromine radical anions (Br2.-), oxygen, and superoxide radical (O2.-) with three cephalosporins have been studied. Absorption spectra and rate constants have been determined. It has been found that both eaq- and .OH quickly react (k congruent to 10(10) mol-1 L s-1) with the molecules to give radicals with similar absorption spectra. N3. gives an absorption spectra that has been attributed to an electron transfer, whereas a part of .OH and Br2.- could add themselves to an unsaturated bond. PMID- 7797092 TI - Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis. AB - We investigated the effect of correcting beta-carotene deficiency in cystic fibrosis (CF) patients on two parameters of lipid peroxidation. The resistance to oxidation of low density lipoprotein (LDL) was measured by the lag time preceding the onset of conjugated diene formation during exposure to copper(II) ions, and lipid peroxide formation was quantitated by malondialdehyde concentrations in plasma (TBA/HPLC method). Simultaneously, alpha-tocopherol and beta-carotene concentrations were determined in LDL and in plasma. Thirty-four CF patients were investigated before and after 3 months of oral beta-carotene supplementation. Beta-carotene concentrations increased (p < 0.0001) in plasma (mean +/- SD) (0.09 +/- 0.06 vs. 1.07 +/- 0.86 mumol/l) and in LDL (0.02 +/- 0.02 vs. 0.31 +/- 0.28 mol/mol), without significant changes in alpha-tocopherol, either in plasma (24.7 +/- 5.9 vs. 25.4 +/- 7.6) or in LDL (8.47 +/- 2.95 vs. 9.05 +/- 4.13). Lag times, being shorter (p < 0.05) in patients than in controls, increased from 48.5 +/- 21.3 to 69.1 +/- 27.9 min (p < 0.001) and plasma MDA concentrations, being greater (p < 0.0001) in patients than in controls, decreased from 0.95 +/- 0.32 to 0.61 +/- 0.15 mumol/l (p < 0.0001). At 3 months, lag times and MDA concentrations did not any longer differ between patients and controls. These data suggest that excess lipid peroxidation occurring in beta-carotene deficiency can be limited and normalized during efficient beta-carotene supplementation in CF patients. PMID- 7797094 TI - Simultaneous generation of nitric oxide and superoxide by inflammatory cells in rats. AB - It has recently been shown that peroxynitrite anion is a powerful oxidant than can initiate lipid peroxidation. As this oxidant is the product of the reaction between nitric oxide and superoxide, we have studied whether cells isolated from an inflammatory exudate can release both radicals simultaneously under physiological conditions. The carrageenin-induced granuloma model in rats was used. Cells from the inflammatory pouch were stimulated with opsonized zymosan in the absence or in the presence of exogenous L-arginine. Nitric oxide production without exogenous L-arginine was detectable after 15 min (0.29 nmol NO2-) and increased with time (1.65 nmol NO2- at 4 h). When nitrite released from cells was expressed as a rate a burst was shown in the first few minutes. Between 0 and 15 min, cells produced NO2- at the following rates: 20 pmol NO2-/1 x 10(6) cells/min without exogenous L-arginine and 83 pmol NO2-/1 x 10(6) cells/min with exogenous L-arginine. Production was further stimulated with opsonized zymosan (92 pmol NO2 /1 x 10(6) cells/min), and inhibited by L-NMMA and L-NIO. The production of superoxide increased for up to 2 h and then stabilized. A significant increase in nitrite was observed in the presence of SOD, whereas L-NIO increased superoxide generation. These results suggest that peroxynitrite anion may be formed by inflammatory cells. PMID- 7797095 TI - Free radical production in nicotine treated pancreatic tissue. AB - The ability of nicotine to induce oxidative stress in the pancreatic tissue of rats was investigated. Homogenized pancreatic tissue of Sprague-Dawley rats was incubated with nicotine in a dose of 200 ng/mg protein/ml for 15, 30, 45, and 60 min or was incubated for 30 min with nicotine in a dose of 50, 100, 200, 400, and 800 ng/mg protein/ml. Pancreatic tissue was also incubated with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a positive correlation between the duration of nicotine incubation and chemiluminescence (r = 0.6) or lipid peroxidation (r = 0.71) and also between the nicotine dose and chemiluminescence (r = 0.54) or lipid peroxidation (r = 0.66). Thirty minutes incubation of pancreatic tissue with nicotine in a dose of 200 ng/mg protein/ml increased chemiluminescence 5 fold and lipid peroxidation 2.5 fold. This response was dampened by SOD or catalase and abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the pancreatic tissue of rats. PMID- 7797097 TI - Metal-catalyzed oxidation of bovine neurofilaments in vitro. AB - Neurofilaments (NF) are important determinants of the shape and size of nerve cells. The oxidation of NF, relevant to aging, neurodegenerative disorders, and axonal (Wallerian) degeneration, has not been studied. In this investigation, we have combined biochemical and ultrastructural methods to study the metal catalyzed oxidation (MCO) of bovine NF using an ascorbate/Fe+3/O2 system. The oxidation of NF proteins was documented by increases in carbonyl content, which were time- and concentration-dependent. Polyacrylamide gel electrophoresis (PAGE) and immunoblot analyses revealed the fragmentation of oxidized NF proteins, predominantly NF-H and NF-M. Electron microscopy (EM) showed that oxidized NF formed dense aggregates and bundles of laterally aggregated filaments. Finally, we also demonstrated that oxidized NF proteins were more susceptible to calpain proteolysis. In view of the growing evidence supporting increased oxidative stress on the nervous system in aging and the report of Cu/Zn superoxide dismutase mutation in familial motor neuron disease, oxidative injury of NF may be relevant to cell atrophy and degeneration of nerve cells and to the formation of abnormal cytoskeletal structures. PMID- 7797093 TI - Paraquat--a superoxide generator--kills neurons in the rat spinal cord. AB - Microdialysis was used to administer paraquat into the spinal cord of the anesthetized rat to determine the effects of the in vivo generation of the superoxide anion (O2.-) on neurons. Exposure to paraquat caused blockage of axonal conduction, destruction of the cell bodies of neurons, and a general release of amino acids. Thus, paraquat is quite harmful to neuronal tissue. Similarities between paraquat-induced damage and that previously observed from the hydroxyl radical are consistent with paraquat, causing damage by generation of reactive oxygen species and the widespread belief that generation of O2.- initiates the formation of destructive reactive oxygen species in a wide variety of traumas and other disorders. PMID- 7797096 TI - Hazards of antioxidant combinations containing superoxide dismutase. AB - Oxygen free radical scavengers protect against ischemia/reperfusion injury of the kidney in vivo and against hypoxia/reoxygenation (H/R) injury of renal cells in several in vitro systems. In an attempt to maximize renal protection we tested several antioxidants in combination; the individual components had previously reduced reoxygenation injury of hypoxic renal epithelial cells. Both glutathione (GSH; 1 mM) and Cu,Zn-SOD provided significant protection against posthypoxic injury. Surprisingly, the combination of Cu,Zn-SOD plus GSH eliminated protection entirely and was highly toxic to normoxic cells. The toxicity of Cu,Zn-SOD+GSH was not prevented by the iron chelator deferoxamine and was only slightly reduced by the hydroxyl scavenger DMTU. Catalase reversed the toxicity of Cu,Zn-SOD+GSH and provided net protection. Direct measurement of intracellular peroxides using 2,7-dichlorofluorescein quantitated by laser cytometry also revealed enhanced generation of peroxides by cells during H/R when Cu,Zn-SOD+GSH was present. GSSG was less toxic than GSH when combined with Cu,Zn-SOD. Importantly, the combination of Mn-SOD+GSH provided superior protection to either agent alone. In the presence of added GSH, heated or autoclaved Cu,Zn-SOD was still toxic, whereas SOD free of chelatable Cu++ was benign. In the presence of GSH, Cu++ derived from SOD may promote the formation of toxic thionyl radicals, metal centered radicals, and/or H2O2, thereby causing cell injury. Great care should be used in designing and interpreting studies employing combinations of antioxidants. PMID- 7797098 TI - Redox intermediates of flavonoids and caffeic acid esters from propolis: an EPR spectroscopy and cyclic voltammetry study. AB - The redox properties of flavonoids: chrysin (1), tectochrysin (2), galangin (3), isalpinin (4), pinostrobin (5), pinobanksin (6), pinobanksin-3-acetate (7), and of caffeic acid ester (8) and diacetylcaffeic acid ester (9), all isolated from propolis, were investigated by cyclic voltammetry in acetonitrile. The choice of aprotic solvent lowered the reactivity of the radical intermediates and made possible to identify redox steps and intermediates not detected so far. The oxidation potentials (vs. saturated calomel electrode) of the investigated compounds were in the region of 1.5 V for 3 and 4; 1.9 V for 1, 2, and 5; 2.0 V for 6 and 7; 1.29 V for 8; and 2.3 V for 9. These oxidation potentials were mainly influenced by the presence of a double bond in 2,3-position and substituent R1 in position 3. Comparison with our earlier data revealed that flavonoids, 1-4, and caffeic acid ester 8 with lower oxidation potentials showed the maximal lipid antioxidant activity, whereas those with higher potentials (5, 6, 7, and 9) are less active. On reduction of 1-9 several one-electron-steps were typically observed in the potential regions: -1.5 V, -1.8 V, and -2 V. where in simultaneous EPR experiments anion radicals of 1 and 3 were observed with the center of unpaired spin density on ring A. Upon oxidation of flavonoids 1-4 carbonyl carbon-centered radicals, .C(O)R, were identified as consecutive products using the EPR spin trapping technique. PMID- 7797099 TI - Cytolysis does not per se induce lipid peroxidation: evidence in man. AB - An increasing bulk of data counters the opinion that cell death and lysis necessarily trigger the formation and release of detectable amounts of molecules that are markers of lipid peroxidation. Plasma levels of thiobarbituric-acid reacting compounds, protein-aldehyde fluorescent adducts, lipid peroxides, and endogenous antioxidant compounds were monitored versus controls, during intensive care treatment, in six patients seriously poisoned by ingestion of the mushroom Amanita Phalloides. All six patients showed cytolysis, and four of them massive tissue necrosis, as monitored in terms of serum transaminases. In all six patients, however, the blood parameters of redox equilibrium measured were within the normal range for the whole observation period. PMID- 7797100 TI - Effects of indolinic and quinolinic aminoxyls on protein and lipid peroxidation of rat liver microsomes. AB - A study on peroxyl radical induced oxidation of rat liver microsomal membranes in the presence of different indolinic and quinolinic aminoxyls (Scheme 1) was carried out in order to test their efficiency as antioxidants in lipid and protein peroxidation. The extent of lipid peroxidation was quantified by the amount of malondialdehyde (MDA) produced, and the measurement of carbonyl residues was used as an index of microsomal protein oxidation. The results obtained suggest that lipid soluble indolinic and quinolinic aminoxyls are efficient in protecting lipids and proteins of biological membranes against oxidation. The efficacy of these aminoxyls as protectors of lipids and proteins was much higher than the water soluble TEMPOL. Moreover, the hydrophobic aminoxyls were more effective in preventing protein than lipid oxidation at low concentrations (1-20 microM). However, at high concentration (100 microM), lipid as opposed to protein oxidation was almost completely inhibited. The data supports the hypothesis that proteins probably have a different oxidation pattern from lipids. PMID- 7797101 TI - Artemia salina as a test organism for measuring superoxide-mediated toxicity. AB - The purpose of this study was to examine the possibility of using Artemia salina as a test organism in the search for compounds having the ability to protect against superoxide-mediated toxicity. The basic procedure for the assay using Artemia salina was performed as described in previous literature, with minor modifications. We found that Artemia salina are extremely sensitive to menadione bisulfite, a compound whose toxicity is probably mediated by intracellular superoxide generation. Desferrioxamine (desferal), a compound with known protective effects, was shown to display dramatic protective activity in our system. We also observed that an inhibitor of endogenous superoxide dismutase (SOD) activity increased the toxicity of menadione toward Artemia salina. In conclusion, this simple, inexpensive, and convenient assay could be a valuable addition to a screening effort in the search for compounds that will be protective against damage by superoxide or other active oxygen species. PMID- 7797103 TI - Reactions of copper(II)-oligopeptide complexes with hydrogen peroxide: effects of biological reductants. AB - Cu(II) complexes with oligopeptides containing histidyl residue in the second or third position could scarcely activate hydrogen peroxide (H2O2), but they could activate H2O2 to yield hydroxyl radical (.OH) in the presence of biological reductants such as cysteine and ascorbic acid. Further, DNA single strand breakage was also observed during the reactions of Cu(II) glycylglycylhistidylglycine (GGHG) with H2O2 in the presence of same biological reductants. PMID- 7797102 TI - Direct measurement of superoxide-dependent chemiluminescence from rat skin following UV-dependent fluoroquinolone-induced dermatitis. AB - Fluoroquinolones are widely used for the treatment of bacterial infection. However, some members of the group cause UV-dependent dermatitis. Therefore, animal models are required to screen and predict if a derivative is likely to cause photodermatitis. Under anaesthesia, the hair on the dorsal side of rats was shaved, then a fluoroquinolone derivative, Y-26611 or ofloxacin was administered subcutaneously (SC) followed by irradiation of a 3 cm diameter circular area of the skin with UV-B(ultraviolet-B) for 45 min. Peak photodermatitis was observed 24 h after irradiation in Y-2611-treated skin. Leucocyte infiltration into the skin, mostly polymorphonuclear leucocytes, was verified by histological techniques. O2.- radical generated by activated leucocytes was detected directly from the skin by SC application of a sensitive O2.- -dependent luminescence reagent, MCLA. O2.- -dependent photon emission (chemiluminescence) from the skin was amplified by phorbol myristate acetate and was markedly suppressed by superoxide dismutase. This is the first report of direct detection of chemiluminescence from the skin of a living animal. PMID- 7797105 TI - The effect of fatty acid unsaturation on the antioxidant activity of beta carotene and alpha-tocopherol in hexane solutions. AB - The effect of fatty acid unsaturation on the antioxidant ability of beta-carotene and alpha-tocopherol to inhibit azobis-isobutyronitrile AIBN)-induced malondialdehyde (MDA) formation is investigated in a hexane solution. A positive correlation is shown between the fatty acid unsaturation and MDA production in homogeneous solutions. Both beta-carotene and alpha-tocopherol act as chain breaking antioxidants in our model, effectively suppressing AIBN-induced MDA formation. When alpha-tocopherol is added to fatty acid solutions, a lag phase of about 30 min is observed and a propagation phase is produced at a rate dependent on the degree of unsaturation and similar to that observed in the absence of the antioxidant. A specific inhibition of initiation phase by alpha-tocopherol is confirmed by its total consumption after 30 min of incubation with AIBN. On the other hand, when beta-carotene is added, a lag period is not observed and the inhibition of propagation phase progressively increases in relation to the degree of fatty acid unsaturation. These data present different antioxidant roles for beta-carotene and alpha-tocopherol in AIBN-induced lipid peroxidation and suggest that beta-carotene can be a very effective antioxidant in highly unsaturated membranes, such as those enriched with n-3 polyunsaturated fatty acids (PUFA). PMID- 7797104 TI - Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers. AB - Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r 0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress. PMID- 7797107 TI - Comments on the glutathione-ascorbic acid redox couple. PMID- 7797106 TI - Protection of vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, coenzyme Q0, coenzyme Q10, beta-carotene, canthaxanthin, and (+) catechin against oxidative damage to rat blood and tissues in vivo. AB - Male Sprague-Dawley rats were fed either a vitamin E and selenium deficient diet, a diet supplemented with vitamin E and selenium, or a diet supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, Beta carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin. Rats were injected with CBrCl3 (0.05 mmol/100 g body weight) intraperitoneally. Oxidative damage to tissues was measured by formation of oxidized heme proteins (OHP) in blood, liver, kidney, heart, lung, and spleen. Diets supplemented with antioxidants showed protection against oxidative damage caused by CBrCl3. The protection was dependent on the diversity and quantity of antioxidants in the diet. In general, diets supplemented with both fat soluble and water soluble antioxidants provided better protection than diets supplemented only with vitamin E and selenium or with vitamin E, selenium, and fat soluble antioxidants. PMID- 7797108 TI - A new class of colorectal cancer gene. PMID- 7797110 TI - Recent advances in the endoscopic management of variceal bleeding. AB - For the first time the endoscopist has more than one option for the management of gastro-oesophageal varices. It is now feasible to select the appropriate therapy on the basis of the clinical setting. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from oesophageal varices, and could be followed two or three days later by banding ligation. Earlier obliteration of varices with this technique may offer the prospect of only two or three sessions of therapy. The availability of the tissue adhesives and thrombin as injectates for fundal gastric varices provide the option of an initial attempt at endoscopic therapy in this high risk group. PMID- 7797109 TI - Liver transplantation for hepatocellular carcinoma. PMID- 7797111 TI - Effect of topical oesophageal acidification on human salivary and oesophageal alkali secretion. AB - Recent human studies suggest that oesophageal HCO3- secretion, in conjunction with salivary HCO3- secretion and secondary oesophageal peristalsis, is important for the protection of oesophageal mucosa from refluxed gastric contents. This study evaluated simultaneously the responsiveness of oesophageal and salivary HCO3- secretion to oesophageal acidification in eight healthy subjects. A 10 cm segment of oesophagus was perfused at a constant rate of 5 ml/min with a specially designed tube assembly. Saline was used initially, and then 10 mM and 100 mM HCl. The perfusates contained 3H-polyethylene glycol (PEG) as a concentration marker to determine volumes. Corrections were applied for a small degree of contamination by swallowed saliva and refluxed gastric alkali. Oesophageal perfusion with 10 mM HCl did not cause symptoms (nausea and heartburn), but tripled the oesophageal HCO3- output from a baseline of 51 mumol/10 cm/10 min (p = 0.021), while doubling the rate of salivary HCO3- secretion from a median basal value of 140 mumol/10 min (p = 0.021). Oesophageal perfusion with 100 mM HCl was associated with symptoms of nausea and heartburn in all subjects. The median oesophageal HCO3- output increased 32 fold to 1659 mumol/10 cm/10 min (interquartile range 569 to 3373; p = 0.036), and salivary HCO3- secretion approximately tripled from basal values (p = 0.036). In conclusion, oesophageal acidification stimulates both salivary and oesophageal HCO3- secretion, responses which may be protective to the oesophageal epithelium. PMID- 7797112 TI - Endoscopic detection of ischaemia with a new probe indicates low oxygenation of gastric epithelium in portal hypertensive gastropathy. AB - Changes in mucosal blood flow may be important in the pathogenesis of many conditions. Study of mucosal blood perfusion is difficult, and available methods have significant technical limitations. This study describes the development of an instrument for endoscopy, which indicates blood flow indirectly, by measuring the quantity of tissue oxygen that can diffuse from the mucosa to a luminal surface electrode. The instrument was used through an endoscope in patients with portal hypertension (n = 14), scleroderma (n = 3), disease controls (n = 7), and normal controls (n = 11). In portal hypertension readings were one quarter that in normal controls in both antrum (geometric mean (SEM) 35 (1.1)), nanoamps v 137 (1.1), and upper corpus 34 (1.1) v 125 (1.1)). Scleroderma patients showed greatly reduced oxygen readings in both antrum (18 (1.2)) and corpus (24 (1.2)), an expected but hitherto undiscovered result. These differences are highly significant (p = 0.0001), and the findings suggest that tissue hypoxia may contribute to mucosal changes in portal hypertensive gastropathy and in scleroderma. PMID- 7797113 TI - Non-steroidal anti-inflammatory drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells. AB - The effects of aspirin and ibuprofen on pepsinogen secretion were studied in isolated human peptic cells prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and percoll gradient centrifugation. Pharmacological concentrations of aspirin and ibuprofen (10(-8)-10(-4) M), potentiated histamine (10(-6)-10(-4)M) and forskolin (10(-5)M) stimulated pepsinogen secretion without affecting basal secretion, acetylcholine (10(-6)M) stimulated pepsinogen secretion or cell vitality. Augmentation of secretagogue stimulated pepsinogen secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium. Cimetidine inhibited the potentiation effect on histamine but not on forskolin stimulated pepsinogen secretion, thus suggesting that this augmentation was independent of histamine H2 receptors. Of interest, potentiation was also independent of endogenous prostaglandin inhibition because exogenous addition of prostaglandin E2 and D2 increased both basal and acetylcholine stimulated pepsinogen secretion in a dose dependent way, but they did not modify histamine or histamine plus aspirin or ibuprofen stimulated pepsinogen secretion. In conclusion, aspirin and ibuprofen potentiate secretagogue stimulated pepsinogen secretion by dispersed human peptic cells and this might be an additional mechanism of non-steroidal anti-inflammatory drug (NSAID) induced gastric injury. This potentiation effect is regulated by calcium, independent of endogenous prostaglandin inhibition and seems to act on pepsinogen secretion at a post receptor site. PMID- 7797115 TI - Prevalence of Helicobacter pylori in patients with gall stones before and after cholecystectomy: a longitudinal study. AB - Fifty six patients with gall stones were enrolled in this study to assess the presence of Helicobacter pylori in gastric mucosa before and after cholecystectomy. Samples were taken from gastric juice and antral mucosa through endoscopy performed on these patients before and after the operation. Gastric juice was examined for bile salt concentration as an indicator of duodenogastric reflux. Antral mucosa was studied for the presence of H pylori and inflammatory response. Duodenogastric reflux was significantly increased (p < 0.001) and H pylori significantly decreased (p < 0.01) in the postoperative period. Mucosal inflammation and its activity were less in the postoperative period but the differences did not reach statistically significant values. PMID- 7797114 TI - Detection of the intragastric sites at which Helicobacter pylori evades treatment with amoxycillin and cimetidine. AB - Treatment of Helicobacter pylori infection with amoxycillin is known to reduce the bacterial load to undetectable levels, while not eradicating the infection. It seems, therefore, that bacteria escape treatment at a 'sanctuary site'. This study examined whether such a site existed in the gastric antrum, body, or fundus. Twenty two patients with H pylori infection and duodenal ulcer disease were treated for one week with amoxycillin (500 mg three times a day) and cimetidine (800 mg at night). Before treatment, H pylori was detected throughout all stomachs, and 13C-urea breath testing at least 28 days after treatment confirmed that eradication of H pylori had occurred in no patients. While under treatment, H pylori was sought by conventional methods and by polymerase chain reaction assay and was found in the gastric fundus in 13 of 22 subjects, in the body in 10 of 22, and the antrum in three of 22: the difference between fundus and antrum was significant (p < 0.01). The continued antral infection in three subjects may have resulted from generalised treatment failure as two of three had H pylori detected throughout the stomach, and these two had compiled relatively poorly with treatment. This study suggests that amoxycillin and cimetidine are relatively effective at clearing H pylori from the gastric antrum, but that escape from treatment may occur in the gastric body, and especially the fundus. PMID- 7797116 TI - Primary gastric lymphoma in clinical practice 1973-1992. AB - This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone. PMID- 7797117 TI - Preservation of the spleen improves survival after radical surgery for gastric cancer. AB - One hundred and ninety five consecutive, potentially curative resections for adenocarcinoma of the stomach were performed in one surgical department between 1970 and 1989: 76 patients underwent gastrectomy with splenectomy and 119 gastrectomy without splenectomy. Operative mortality was 12% after gastrectomy with splenectomy, but only 2.5% after gastrectomy without splenectomy (p < 0.05). Postoperative complications were also significantly more common when splenectomy was combined with gastrectomy (41% v 14%, p < 0.01). Cumulative five year survival was 45% after gastrectomy with splenectomy, compared with 71% after gastrectomy alone (p < 0.01). When the results of the two groups of patients were compared, stage for pathological stage, no evidence was found that splenectomy improved survival. Application of Cox's proportional hazards model, which makes allowance for other variables such as the T and N stages, showed that splenectomy had an adverse influence on patients' survival. Splenectomy does not benefit the patient and its routine use in the course of radical resections for carcinoma of the stomach should be abandoned. PMID- 7797119 TI - South Asian and European colitics show characteristic differences in colonic mucus glycoprotein type and turnover. AB - South Asians in Britain have a high incidence of ulcerative colitis and a low incidence of colorectal cancer. The pattern of mucus production in 12 South Asian and 16 European colitics and a control group of 19 South Asians was studied. Three types of mucin were identified after organ culture of colonic biopsy specimens with a dual label of [3H]-glucosamine and sodium [35S]-sulphate: type A had a high [35S]:[3H] ratio and high incorporation ([3H] dpm/micrograms DNA > 500); type B had a low ratio and high incorporation; and type C had low incorporation but with either high (C1) or low (C2) ratios. European colitic mucins show a significant reduction in the level of sulphation detected by mucin histochemistry with high iron diamine/Alcian blue staining, together with predominantly type B or C2 mucins (low sulphation). South Asian colitics showed histochemically normal patterns of high sulphation and largely type A and C1 mucins (high sulphation). There was no correlation of mucin type with disease activity index in either ethnic group. The appearance of apparently normal mucin in patients with ulcerative colitis may be a useful marker for the identification of a subgroup at low risk of colorectal cancer. PMID- 7797118 TI - Colonic cell proliferation in two different ethnic groups with contrasting incidence of colon cancer: is there a difference in carcinogenesis? AB - Most studies on colorectal carcinogenesis suggest a field defect, preceding overt development of cancer. The low incidence of adenomatous polyps in the African population, however, suggests that there may be an alternative route for cancer development. The aim of the study was to discover if the difference in incidence of colorectal cancer in Africans compared with the white population is reflected in a different pattern of cell proliferation. Histological normal mucosa from 30 patients (15 white South African (W), 15 South African Africans (A)) with confirmed colon cancer were examined. Proliferating cells were detected using the Ki-67 antigen. In addition, cell proliferation data were obtained, from 30 age matched controls (15 Africans, 15 white South Africans), without colorectal disease. The African controls were significantly younger (mean (SD) (A: 42 (20), W: 66 (13), p < 0.05)) than the white controls. The second control group had a significantly higher mean (SD) total labelling index (W: 11 (3), A: 6 (4), p < 0.05). In addition the proliferative pattern of the white group without evidence of colorectal cancer showed a comparatively large amount of dividing cells in compartment 2, compared with African controls (mean (SD) (W: 21 (8), A: 9 (8), p < 0.05)). Mucosa from Africans with cancer showed a proliferative pattern with the same increased total labelling index (A: 15 (5), W: 16 (6), p = NS, phase II proliferative lesion) and an even more pronounced upward expansion (phase I proliferative lesion) compared with white cancer patients. This suggests that the mechanism of colorectal carcinogenesis is similar in Africans and the white population. The lack of clinical evidence of the adenoma-carcinoma sequence, and the incidence of cancer at a comparatively young age in Africans may be explained by the fact that colorectal cancer in this ethnic group behaves more aggressively and that adenomatous polyps are rapidly converted into overt cancer before detection. PMID- 7797121 TI - Osteoporosis in treated adult coeliac disease. AB - Forty five women and 10 men with coeliac disease diagnosed in adult life, who were already on a gluten free diet, had serial bone mineral density measurements at the lumbar spine and femoral neck over 12 months. Osteoporosis, defined as a bone mineral density (BMD) < or = 2 SD below the normal peak bone mass was found in 50% of male and 47% of female coeliac patients. Patients with a BMD < or = 2 SD below age and sex matched normal subjects, had a significantly lower body mass index (21.3 kg.m-2 compared with 25.2 kg.m-2, p < 0.02 Wilcoxon rank sum test) and lower average daily calcium intake (860 mg/day compared with 1054 mg/day, p < 0.05 Wilcoxon rank sum test) than patients with normal bone mineral density. In postmenopausal women with coeliac disease there was a strong correlation between the age at menopause and BMD at both the lumbar spine (r = 0.681, p < 0.01, Spearman's rank correlation) and femoral neck (r = 0.632, p < 0.01). No overall loss of bone was shown over the 12 months of follow up, and relative to the reference population there was a significant improvement in BMD at the lumbar spine in women (p < 0.025, paired t test) and at the femoral neck in men (p < 0.05, paired t test). There was a significant negative correlation between the annual percentage change in BMD at the lumbar spine and the duration of gluten free diet (r = -0.429, p<0.01, Spearman's rank correlation), with the largest gain in BMD in patients with most recently diagnosed coeliac disease. Osteoporosis was shown in 47% of patients with treated adult coeliac disease. Recognised risk factors for osteoporosis in the general population including low body mass index, dietary calcium intake, and early menopause are particularly important in coeliac disease. Treatment of coeliac disease with a gluten free diet probably protects against further bone loss, and in the early stages is associated with a gain in bone mineral density. PMID- 7797120 TI - Translocation of gliadin into HLA-DR antigen containing lysosomes in coeliac disease enterocytes. AB - Coeliac disease is triggered by ingestion of wheat gliadin and is probably immune mediated. There is evidence by light microscopy that expression of class II major histocompatibility complex (MHC) molecules is increased in the small intestinal epithelium of patients with untreated coeliac disease and that gliadin can be taken up by small intestinal enterocytes. The pathway by which gliadin is transported to class II MHC proteins has not been demonstrated. Using an immunogold technique and thin frozen sections of jejunal biopsy specimens, gliadin, HLA-DR antigens, and IgA were localised at an ultrastructural level in the jejunal epithelium of patients with both untreated and treated coeliac disease and controls. Cathepsin D was used as a marker for late endosomes or lysosomes. The results show that gliadin is translocated into vacuoles positive for HLA-DR antigens as well as cathepsin D in jejunal enterocytes of patients with untreated coeliac disease. Secretory IgA may have a role in this translocation of gliadin, which is a specific event that occurred only in jejunal enterocytes from patients with untreated coeliac disease but not in a patient maintained on a gluten free diet or in controls. These results support a central role for epithelial cells of the human intestinal mucosa in the transport of gliadin to an HLA-DR positive compartment which precedes antigen presentation of gliadin to antigen sensitive T lymphocytes. PMID- 7797122 TI - Duration of recurrent ileitis after ileocolonic resection correlates with presurgical extent of Crohn's disease. AB - Crohn's disease of the terminal ileum recurs in a predictable sequence proximal to the ileocolonic anastomosis after surgical resection. To confirm the suspicion that the duration of recurrent ileitis correlates with the extent of presurgical disease, this study investigated 23 consecutive patients with recurrent Crohn's disease symptoms who had undergone ileocaecal resections between 1982 and 1992 at our institution and had both preoperative and postoperative small bowel follow through studies available for comparison. All films were reviewed by a blinded gastrointestinal radiologist using uniform criteria. Symptomatic recurrence was reported at a mean (SEM) of 29 (25) months after resection. Presurgical length of inflammation averaged 26 (15) (8-57) cm and at recurrence 24 (14) (7-55) cm. The correlation coefficient (r) between pre and postsurgical extent of ileal disease was 0.70 (p < 0.0001). Seven patients had sequential small bowel series after 20 (10) (7-36) months without intervening surgery. The extent of measured inflammation between examinations correlated with r = 0.995 (p < 0.0001), showing the consistency of the measurement process. The close correlation between the duration of postoperative recurrence with the extent of presurgical disease is another example of individual patterns of recurrent Crohn's disease and is an additional factor to be considered when contemplating surgical resections. PMID- 7797123 TI - Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes. AB - The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene. PMID- 7797124 TI - Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29. AB - Normal colonic epithelial cells play an important part in the mucosal immune system and use butyrate, a bacterial fermentation product, as an important energy source. Butyrate deficiency has been associated with inflammatory bowel disease, diversion colitis, and pseudomembranous colitis. Butyrate effects on important molecules for epithelial immune functions were studied in a colonic epithelial cell line (HT-29): the constitutive and cytokine regulated expression of secretory component (poly-Ig receptor), HLA class I and II molecules, and intercellular adhesion molecule-1 (ICAM-1). Butyrate facilitated the constitutive expression of secretory component and HLA class I. Butyrate furthermore tended to enhance cytokine mediated stimulation of protein expression, although tumour necrosis factor alpha (TNF) and interleukin 4 (IL 4) responses on HLA class I and secretory component, respectively, were relatively inhibited by butyrate. Cytokine mediated accumulation in the various mRNAs usually increased even more in the presence of butyrate, with the exception of TNF response on HLA class I and secretory component mRNA concentrations. In conclusion, butyrate may substantially influence constitutive and cytokine mediated expression of molecules with immune functions in a complex and differentiated manner, and butyrate deficiencies, as seen in various clinical conditions, might influence mucosal immune responses. PMID- 7797125 TI - Differential regional effects of octreotide on human gastrointestinal motor function. AB - The effects of octreotide on regional motor function in the human gut are unclear. In a randomised, blinded study the effects of octreotide (50 micrograms, subcutaneously, three times daily) and placebo on gastric, small bowel, and colonic transit, and colonic motility and tone were assessed in 12 healthy volunteers whose colon had been cleansed. Octreotide accelerated initial gastric emptying (p = 0.05), inhibited small bowel transit (p < 0.01), and reduced ileocolonic bolus transfers (p < 0.05). Colonic transit was unaltered by octreotide; the postprandial colonic tonic response was inhibited (p < 0.05 v placebo), whereas colonic phasic pressure activity was increased by octreotide (p < 0.05 v placebo). These data support the use of octreotide in diarrhoeal states but not in diseases that cause small bowel stasis and bacterial overgrowth. Simultaneous measurements of colonic transit, tone, and phasic contractility are valid in studying the effects of pharmacological changes and may be applicable to the study of the human colon in health and disease. PMID- 7797126 TI - Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. AB - Within the multiform liver/kidney microsomal (LKM) family, a subgroup of sera that reacts with a liver cytosolic (LC) protein has been isolated and the new antigen-antibody system is called LC1. Unlike LKM antibody type 1 (anti-LKM1), anti-LC1 is said to be unrelated to hepatitis C virus (HCV) infection and has therefore been proposed as a marker of 'true' autoimmune hepatitis type 2. Altogether 100 LKM1 positive sera were tested by immunodiffusion (ID). Twenty five gave a precipitation line with human liver cytosol; 17 of the 25 also reacted with rat liver cytosol. Thirteen of the 25 sera were anti-HCV positive by second generation ELISA: anti-HCV positive patients were significantly older (p < 0.001) and tended to have less active disease. No difference in anti-LC1 titre or ID immunoreactivity was found between anti-LC1/anti-HCV positive and anti LC1/anti-HCV negative cases. In Western blotting experiments, 14 of 24 ID positive sera recognised a 58 kD protein of the human cytosolic fraction and 11 gave a similar reactivity when tested with human microsomes, suggesting the presence of the LC1 target antigen also in the microsomal preparation. Western blotting reactivity was similar for both anti-HCV positive and negative sera. These data confirm the existence of the LC1 antigen-antibody system that partially overlaps with LKM1, and that it is an additional marker of juvenile autoimmune hepatitis type 2. It does not, however, discriminate between patients with and without HCV infection. PMID- 7797128 TI - Is biliary lithiasis associated with pancreatographic changes? AB - The aetiological role of biliary lithiasis for chronic pancreatitis remains controversial. Previous studies based on pancreatographic studies reported changes in the pancreatic duct system caused by biliary lithiasis. This study analysed retrospectively the endoscopic retrograde cholangiopancreatography of 165 patients presenting with biliary lithiasis and of 53 controls. Among the 165 patients, 113 had choledochal stones (53 with gall bladder stones, 50 had had a cholecystectomy, 10 with a normal gall bladder), 35 had gall bladder stones without choledochal stones, 17 had cholecystectomy for gall bladder stones. Pancreatograms were analysed by measuring the diameter of the pancreatic duct in the head, the body, and the tail of the pancreas, and evaluating the regularity of the main pancreatic duct and the presence of stenosis, the regularity or the dilatation of secondary ducts, and the presence of cysts. In addition, we established a score, based on the above parameters, by which pancreatograms were classified as normal or with mild, intermediate, moderate or severe abnormalities. A multivariate analysis (stepwise multiple discriminant analysis) was performed for age, sex, presence of gall stones, presence of choledochal stones. Patients were comparable with controls for sex, alcohol consumption but were younger (55 v 68 years, p < 0.01). In patients and in controls, the frequency of pancreatographic abnormalities increased significantly with age. The pancreatographic features of patients and controls were not significantly different. In the multivariate analysis, age was the only factor with significant predicting value for pancreatographic abnormalities. In conclusion, biliary lithiasis in itself is not an aetiological factor for chronic pancreatitis, older age being responsible for the abnormalities seen by pancreatography of patients with biliary lithiasis. PMID- 7797130 TI - Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography. AB - The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p < 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation. PMID- 7797127 TI - Effect of octreotide on fasting gall bladder emptying, antroduodenal motility, and motilin release in acromegaly. AB - Subcutaneous octreotide (Sandostatin) injections lead to gall stone formation in 13-50% of acromegaly patients during one year of therapy. This study explored the effects of octreotide on interdigestive gall bladder emptying, antroduodenal motility, and motilin release. Ambulatory antroduodenal manometry was performed in six acromegaly patients before and after two months of octreotide therapy (100 micrograms thrice daily, subcutaneously). Ultrasonographic gall bladder volume measurements and plasma motilin concentrations were obtained during two migrating motor complex (MMC) cycles. Before octreotide treatment, nine of 26 phase III activities started in the antrum and 17 of 26 in the duodenum whereas during treatment 47 of 48 of phase III activity started in the duodenum (p < 0.05). Before treatment, interdigestive gall bladder emptying (mean (SEM) 39.9 (4.0)% of maximal fasting volume) and plasma motilin peaks preceded antral phase III but not duodenal phase III. During octreotide therapy no significant motilin fluctuation or gall bladder emptying was seen. Fasting gall bladder volume increased from 40.9 (9.1) ml before to 68.0 (14.8) ml (p < 0.05) during octreotide treatment. In conclusion, two months' treatment with octreotide increases the number of duodenal phase III like activity and virtually abolishes antral phase III, plasma motilin peaks, and interdigestive gall bladder emptying. These effects might contribute to the high risk of gall stone formation during longterm octreotide treatment. PMID- 7797129 TI - Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy. AB - The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin. PMID- 7797131 TI - Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours. AB - Differential diagnosis of pancreatic cancer and chronic pancreatitis is sometimes difficult and cytological examination of brushings or aspirated material collected during endoscopic retrograde cholangiopancreatography (ERCP) remains disappointing. As point mutations in codon 12 of the c-Ki-ras 2 gene are found in most pancreatic adenocarcinoma and not in chronic pancreatitis, this study analysed prospectively the presence of these mutations in brushing samples collected during ERCP in 45 patients (26 males, 19 females) showing a dominant stricture of the main pancreatic duct at pancreatography: 24 with pancreatic adenocarcinoma, 16 with chronic pancreatitis, and five intraductal mucin hypersecreting neoplasms. Twenty of 45 patients presented equivocal ERCP findings that did not permit a definite diagnosis. Ki-ras mutations at codon 12 were detected using a rapid and sensitive method based on polymerase chain reaction mediated restriction fragment length polymorphism analysis and confirmed by direct sequencing of polymerase chain reaction products. Results were compared with those provided by routine brush cytology. A definitive diagnosis was established for each patient. Mutations were detected in 20 of 24 patients with pancreatic adenocarcinoma (83%), but in none of the chronic pancreatitis patients and intraductal mucin hypersecreting neoplasms, irrespective of their location. By contrast, only 13 of 24 pancreatic adenocarcinoma (54%) were detected by conventional cytological examination, which yielded four false negative and seven non-contributive results. Sensitivity, specificity, and accuracy of molecular biological and cytological methods were 83%-76%, 100-83%, and 90%-58%, respectively. Notably the mutations could be detected in six patients with small tumour size (< or = 2 cm). In conclusion, Ki-ras analysis performed on pancreatic brushing samples is an efficient procedure, more accurate than cytology in the diagnosis of pancreatic adenocarcinoma, and highly specific in the differentiation between neoplastic and chronic inflammatory ductal changes, especially in patients showing inconclusive ERCP findings. PMID- 7797133 TI - Fulminant hepatic failure caused by tuberculosis. AB - A 54 year old Asian woman developed fulminant hepatic failure followed by renal failure. Because of a past history of possible tuberculosis, she was given antituberculous drugs. The chest x ray was normal. A transjugular liver biopsy showed caseating necrosis, granulomas, and acid fast bacilli indicative of miliary tuberculosis. Despite full supportive therapy, her condition deteriorated and she died. Postmortem examination showed widespread miliary tuberculosis; culture confirmed the presence of Mycobacterium tuberculosis. Tuberculosis causes fulminant hepatic failure rarely and only three cases have been described. In this, as with the other cases, hyponatraemia and hepatomegaly were features at presentation. This is the first report of treatment being given before death. PMID- 7797134 TI - The nurse endoscopist. British Society of Gastroenterology. PMID- 7797132 TI - Intestinal fatty acid binding protein is available for diagnosis of intestinal ischaemia: immunochemical analysis of two patients with ischaemic intestinal diseases. AB - Mesenteric infarction and other acute ischaemic intestinal diseases are still a challenging diagnostic problem. Based on animal experiments, intestinal fatty acid binding protein (I-FABP), which is uniquely localised to the bowel, has recently been proposed as a new serum marker for intestinal ischaemia. This paper reports on two cases with acute intestinal ischaemic diseases, and the measurement of serum I-FABP by western blot analysis. The concentrations of ordinary serum markers were normal and the bowel necrosis was not diagnosed until surgical exploration. Immunochemical analysis showed that the I-FABP concentrations in the patients' serum samples were high at the time of admission, and that I-FABP was undetectable in the samples obtained after bowel resection and in healthy control subjects. This paper suggests that I-FABP is released into the circulation in the acute phase of intestinal ischaemia and that I-FABP can be used in establishing the diagnosis of ischaemic intestinal diseases. PMID- 7797135 TI - Light of my life. PMID- 7797136 TI - Postprandial function in gastroparesis. PMID- 7797137 TI - Autoimmunity and chronic pancreatitis. PMID- 7797138 TI - Diagnosis of invasive amoebiasis: renaissance of the morphology era. PMID- 7797140 TI - Cancer surveillance in ulcerative colitis. PMID- 7797139 TI - Relation of acupuncture and vagal gastric acid secretion. PMID- 7797141 TI - [Italian Society of Experimental Hematology. Workshops. Firenze, 24 March and 16 June 1994. Abstracts]. PMID- 7797143 TI - Functional heterogeneity of in vitro selected variants from an IgM-secreting rat immunocytoma. AB - A long-term tissue culture line of highly metastatic IR202 immunocytoma of LOU rats, and five of its clones (B4, C2, C4, C5, and D3) were established and studied comparatively. All such cells were similar in terms of: (i) light microscopic morphology, (ii) growth rate, (iii) saturation density, (iv) cell cycle progression, and (v) cell surface IgM, major histocompatibility complex (MHC) class I and class II antigen expression, but (vi) showed a non-homogeneous pattern of chromosomal constitution, with both numerical and structural abnormalities detected in variable proportions of the different cell variants. Moreover, IR202 variants exhibited a marked difference in the production of soluble factors which was closely associated with the ability of their supernatants to inhibit mitogen (affinity-purified goat F(ab')2 fragments specific for rat mu-chains (anti-mu antibody), lipopoly saccharide (LPS), or concanavalin A (ConA))-induced proliferation of normal splenic B and/or T lymphocytes. These results are consistent with the concept of intratumor heterogeneity and the ability of immunoglobulin-secreting tumors to induce severe immune dysfunction in host animals and humans. PMID- 7797142 TI - Autoimmune haemolysis and red cell autoantibodies with ABO blood group specificity. AB - In order to study red cell autoantibodies with ABO specificity, the records of 4668 patients seen over 32 years were examined. Five group A patients had high thermal amplitude cold agglutinins showing anti-A, -A1 or -AI specificity; none had ever received blood or blood products. They presented as chronic cold haemagglutinin disease, autoimmune haemolytic anaemia or were discovered during investigation of pregnancy, carcinomatosis or anaemia. In vivo haemolysis was evident in all but the antenatal case; only the patient with autoimmune haemolytic anaemia required treatment, responding well to steroids. ABO-specific autoantibodies thus appear similar in reactions and clinical manifestations to autoantibodies in general. PMID- 7797144 TI - Cytochemical determination of monoamine oxidase activity in lymphocytes and neutrophils of schizophrenic patients. AB - Monoamine oxidase (MAO) activity was determined cytochemically in peripheral blood lymphocytes and neutrophils of 14 schizophrenic patients and normal controls. The cytochemical method of Glenner modified for smear preparations was utilized. Schizophrenic patients show a tendency to express a lower percentage of MAO-positive neutrophils as compared to the non-schizophrenic controls. This biochemical difference in schizophrenic patients needs further clarification. PMID- 7797145 TI - Urinary N-acetyl-beta-D-glucosaminidase activity in leukaemic children during high-dose methotrexate therapy. AB - Urinary N-acetyl-beta-D-glucosaminidase (NAG-ase) activity is a very sensitive parameter of kidney proximal tubular damage. Using urinary NAG-ase activity/urinary creatinine as the NAG index, the serum methotrexate (MTX) level and urinary pH were investigated simultaneously. These parameters were measured in 17 leukaemic children. During MTX treatment, NAG indices were normal in 5 children and only slightly elevated occasionally in 9 patients. Among them, transiently high serum MTX levels (Patient A) or low urinary pH (Patient B) were accompanied by high NAG indices. MTX toxicity has been diagnosed in 3 cases, when permanently high NAG indices were in accordance with other clinical signs. PMID- 7797146 TI - Platelet ultrastructural and functional studies in myelodysplasia. AB - We studied the platelets of 8 patients with myelodysplasia aged 49-77 years, using both ultrastructural and functional techniques. Five of the 8 patients were classified as having refractory anaemia, and 3 as refractory anaemia with excess of blasts (RAEB). Electron microscopically, the myelodysplastic patients had in addition to normal ones, platelets containing significantly less alpha-granules. In part of these hypogranular platelets, the dense tubular system was abundant, but in contrast with normal platelets, it was not dispersed between the other organelles, nor did it form a membrane complex with the open cannalicular system. From a functional point of view, collagen-induced shape change was the most frequently disturbed parameter: there was a total loss of collagen-induced shape change in 5 patients. In 2 patients, there was a complete lack of response to collagen in platelet-rich plasma (both shape change and aggregation); in one of them, there was also a total loss of adenosine triphosphate secretion in response to all inducers tested. After 4 years of follow-up, 5 patients had died, of whom 3 were RAEB patients. An initial complete absence of collagen-induced shape change was found in these 5 patients, while in the 3 patients who were still alive at the end of the follow-up period, collagen-induced shape change was normal in 2 and slightly diminished in one. PMID- 7797147 TI - Hemorrhagic pleural effusion as a complication of chronic lymphocytic leukemia. AB - We report a case of hemorrhagic pleural effusion in a 59-year-old-man with chronic lymphocytic leukemia (CLL). The association between pleural effusion and CLL has been rarely reported and we believe that the pleural effusion probably reflected an advanced and refractory disease in our patient. Early detection of this complication is essential for appropriate therapy. PMID- 7797149 TI - [Treatment of obstructive sleep apnea with anterior mandibular positioning device]. AB - The efficacy of the anterior mandibular positioning (AMP) device in obstructive sleep apnea syndrome was assessed. This device advances the mandible anteriorly by approximately 5-7 mm. 29 patients were examined and questioned about temporomandibular (TM) and facial pain before and after treatment with the device. Polysomnographic sleep studies were performed on all before, and 2 weeks after continuous use of the AMP device. 10 of the patients also underwent polysomnographic follow-up after 1 year. The mean apnea index (AI) before treatment was 40.1, which decreased to 24.3 (p < 0.0001) after 14.3 days of treatment with the AMP device. O2 saturation also increased, from 84.2% before, to 89.2% after treatment (p < 0.002). In 10 patients the mean AI after 1 year was 24.9, not different from that after only 2 weeks of treatment, but significantly different from their mean AI before treatment (39.8). Use of the AMP device did not change blood saturation levels; neither did it affect dental status, action of the masticatory muscles, nor did it cause TM joint dysfunction. 21 patients (72.4%) have now been fitted with an AMP device, and the mean follow-up is 13.4 months (range 2-22); 3 have been using the AMP only intermittently for TM joint pain or discomfort. We conclude that the AMP device helps the majority of patients and is an alternative, nonsurgical method for treating obstructive sleep apnea syndrome. PMID- 7797150 TI - [Flexible bronchoscopy in the diagnosis of foreign body aspiration]. AB - Foreign body aspiration (FBA) should be suspected in every child with acute onset of cough or wheezing. Although a choking episode occurs in 80-90% of cases of FBA, it is not necessarily diagnostic. Furthermore, in many cases neither physical examination nor chest x-ray, including fluoroscopy, are diagnostic; their results may be completely normal in up to 17-25% of cases of FBA. Bronchoscopy is therefore mandatory when there is a convincing history of FBA, regardless of physical or radiologic findings. This can be done with either the flexible or rigid bronchoscope, or with both. PMID- 7797152 TI - [Laparoscopic splenectomy for immune thrombocytopenic purpura]. AB - Splenectomy is effective in treating immune thrombocytopenic purpura (ITP). Recent advances in laparoscopic technique and technology have made laparoscopic splenectomy feasible. We performed it in 8 cases of ITP (16-34 years old, and 2 24 months after the diagnosis was made and appropriate treatment started). Indications for splenectomy were no response to corticosteroid therapy (2 patients), decrease in platelet count when attempting to taper off therapy (3), or severe side-effects of the treatment (3). 4-5 ports were used. The splenic artery was first double-clipped through an opening in the gastrocolic ligament and then the lower splenic pole and the posterolateral attachments were dissected using endoclips and electrocautery. The hilum and short gastric vessels were separated using an endostapler. The spleen was placed in a plastic bag whose open end was pulled out through an umbilical incision and the spleen fragmented and aspirated out of the bag, while it was still inside the abdomen. Blood or platelet transfusions were not needed and the postoperative course was uneventful in all, with early return to full normal activity. Postoperatively, platelets increased to more than 150,000/mm3 in all patients, and there was no further need for corticosteroids during a follow-up of 2-12 months. We recommend laparoscopic splenectomy for ITP because of the reduced operative trauma, better recovery and rehabilitation, less postoperative pain, cosmetic advantage, and possibly fewer postoperative complications. PMID- 7797148 TI - [Screening and treatment of hyperlipidemias in Israel]. AB - Hyperlipidemias are a major risk factor for cardiovascular disease. Screening and treatment guidelines for the metabolic disorders associated with them have been adopted and published by the Israel Atherosclerosis Society. We examined the frequency of plasma lipid determinations and treatment of hyperlipidemia by a sample of family practitioners, primary physicians, cardiologists and internists working in ambulatory, primary medical care who filled out questionnaires for consecutive adult clinic patients. Of 2015 patients, 1029 (51%) were reported to be free of cardiovascular disease or its risk factors, 606 (30%) had at least 1 risk factor, 171 (8%) had peripheral or cerebrovascular atherosclerotic disease, 131 (7%) had had a myocardial infarction and 78 (4%) had undergone coronary angioplasty or bypass surgery. Although the frequency of determinations of total HDL and LDL cholesterol increased from those without a risk factor to those after bypass surgery, the overall rates were lower than expected in all groups. With regard to risk factors, in those with a family history of cardiovascular disease lipid determinations were done most frequently, approaching the frequency in the bypass group. Combined hypercholesterolemia and hypertriglyceridemia was the most common metabolic aberration in all categories. The rate of drug therapy increased from those with no risk factor to those after bypass surgery. Therapy with resin was reported in 3-14%, fibric acid derivatives in 29-53% and statins in 33-57% of the various patient groups. Again, the drug therapy profile of the group with a positive family history was similar to that of the bypass group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797153 TI - [Renal tubular dysgenesis]. AB - Renal tubular dysgenesis (RTD) is a very rare malformation, only 24 cases having been described. We present the case of twins born after 28 weeks gestation to a newly-arrived Ethiopian immigrant in whom oligohydramnios was diagnosed when she was admitted. 1 twin had developed polyhydramnios, died before birth and was born with hydrops fetalis. The other newborn suffered from pulmonary distress and anuria, and died 2 days after birth. At autopsy there were no apparent changes in the kidneys or urinary tract, but histological examination showed absence of proximal convoluted tubules. This was attributed to RTD and confirmed by histochemical examination. PMID- 7797154 TI - [Polymyalgia rheumatica as the presenting symptom of multiple myeloma]. AB - Polymyalgia rheumatica is a clinical syndrome which appears after the age of 50 and is characterized by pain and stiffness of proximal muscles, rapid sedimentation rate and a dramatic response to small doses of corticosteroids. The linkage between polymyalgia rheumatica and temporal arteritis is well-known, but the connection with monoclonal gammopathy and lympho-proliferative disorders has rarely been reported. We present a 74-year-old man admitted with the typical clinical picture of polymyalgia rheumatica, which was the presenting symptom of monoclonal gammopathy and subsequently-diagnosed multiple myeloma. PMID- 7797155 TI - [Importance of early diagnosis of hyperlipidemias in the prevention of atherosclerosis]. PMID- 7797156 TI - [Laparoscopic surgery]. PMID- 7797151 TI - [Laparoscopic colonic resection]. AB - We present our initial experience with laparoscopic colonic resection in 15 patients: adenocarcinoma of the colon, 10 cases, giant villous adenoma (2), arteriovenous malformation (2), and a case of benign stricture. Mean operating time was 190 minutes and there were no intraoperative complications. The margins of resection and number of resected lymph nodes in patients with malignancy were comparable to those in the conventionally operated. Mean postoperative hospital stay was 6.1 days. During a maximum follow-up of 15 months there were no wound or trocar-site recurrences. We conclude that laparoscopic colonic resection is technically feasible and safe. However, its use for treating malignant diseases of the colon needs further study. PMID- 7797157 TI - [Detection and treatment of high blood cholesterol for prevention of coronary heart disease--attitude of the Israel Society of Atherosclerosis]. PMID- 7797159 TI - [Impact of hormone replacement therapy on the cardiovascular system]. PMID- 7797158 TI - [Principles of dietary treatment in hyperlipidemia]. PMID- 7797160 TI - [Drug therapy for the treatment of hypercholesterolemia in adults]. PMID- 7797161 TI - [Technology in need of assessment: total hip arthroplasty]. PMID- 7797163 TI - [Fragile X syndrome: molecular aspects and prenatal diagnosis]. PMID- 7797162 TI - [Prevention and treatment of infected total hip arthroplasty]. PMID- 7797167 TI - Exotic plant species can serve as staple food sources for wild howler populations. PMID- 7797165 TI - Influence of infants on female social relationships in monkeys. AB - A critical evaluation of the literature and a cost/benefit analysis suggest that changes in affiliation patterns in female monkeys following the birth of infants should be mediated by female reproductive state and dominance rank and infant characteristics such as age and sex. Several predictions concerning the effects of these variables were tested on dyadic interactions between lactating pigtail macaque (Macaca nemestrina) females and other lactating or pregnant females. Dyads composed of lactating females spent more time in proximity, contact and grooming than dyads composed of lactating and pregnant females. Association with other lactating females was mainly due to lower-ranking females that may gain benefits such as increased tolerance and support from their partners. Infant handling by lactating females had a higher percentage of harassment episodes than handling by pregnant females. Among dyads composed of two lactating females, affiliative interactions were inversely correlated with rank distance. It is suggested that the presence of infants may influence female social dynamics at the group level to a greater extent than previously thought. PMID- 7797168 TI - Gular scent glands in adult female white-faced saki, Pithecia pithecia pithecia, and field observations on scent-marking behaviour. PMID- 7797164 TI - Contrasting chimpanzees and bonobos: nearest neighbor distances and choices. AB - In an effort to understand factors underlying differences in the social organization of Pan troglodytes and P. paniscus, we measured the nearest neighbor distances and choices for chimpanzees in Kibale National Park, Uganda, and for bonobos in Lomako Forest, Zaire. We assume that the spatial organization of a set of individuals should reflect the underlying relationships between them. Bonobos were found to have smaller nearest neighbor distances than chimpanzees. The distribution and variability of the distances suggested that chimpanzees have a more restricted range of nearest neighbor distances than bonobos, avoiding situations of very close proximity. Selection of the sex of the nearest neighbor by a focal animal differed between the species. For example, male bonobos rarely had another male as their nearest neighbor, while male chimpanzees frequently did. Similarly, male bonobos tended to move apart when observed together, while it was female chimpanzees who tended to move apart when together. These observations are considered with respect to the nature of the social interactions in these species. PMID- 7797166 TI - Temporal patterns in primate leaf eating: the possible role of leaf chemistry. PMID- 7797169 TI - Activity budget and diet of Alouatta caraya: an age-sex analysis. PMID- 7797170 TI - Social organisation and SIV sero-epidemiology of a patas monkey population in Senegal. PMID- 7797171 TI - Effects of vomitoxin (deoxynivalenol) and cycloheximide on IL-2, 4, 5 and 6 secretion and mRNA levels in murine CD4+ cells. AB - The effects of continuous in vitro exposure to the trichothecene, vomitoxin (VT) or another protein synthesis inhibitor, cycloheximide (CHX), on interleukin (IL) secretion and mRNA levels were evaluated in murine splenic CD4+ cells. Significant increases were seen in supernatant IL-2, IL-4 and IL-5 obtained from 7 day Concanavalin A (Con A)-stimulated CD4+ cultures containing VT concentrations of 250, 100 and 100 ng/ml, respectively, compared with controls run in the absence of VT. The effect of VT on CD4+ cell proliferation was also assessed after culturing for 3, 5 and 7 days with Con A. Although total cell numbers were not affected at day 3, cultures at day 5 with 50 or more ng VT/ml and at day 7 with 100 or more ng VT/ml had significantly lower cell numbers than controls. In addition, viable cell number was unaffected at day 3, but was significantly decreased at day 5 by VT concentrations of 12.5 ng or more ml and at day 7 by 100 or more ng VT/ml. Elevations in IL-2, IL-4 and IL-5 were also observed in 7-day Con A-stimulated CD4+ cell cultures containing CHX at 50-100, 50 and 10 ng/ml, respectively. When CD4+ cells were stimulated with Con A in the absence of inhibitors and then subjected to reverse transcriptase-polymerase chain reaction coupled with Southern analysis, maximal IL-2, IL-4 and IL-6 mRNA levels were induced at 48 hr whereas peak IL-5 mRNA was observed at 72 hr. Superinduction of IL-2 mRNAs was observed in the presence of VT at 50-100 ng/ml and CHX at 50-250 ng/ml. IL-4 and IL-5 mRNAs were superinduced by VT at 100 ng/ml and CHX at 50 ng/ml. The results suggest that VT and CHX could superinduce both interleukin secretion and mRNA transcript levels in CD4+ cell cultures and that, for VT, these effects occurred concurrently with inhibition of cell proliferation. PMID- 7797172 TI - Toxicity and cell proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered by gavage. AB - Dose-response relationships were determined for the induction of cytolethality and regenerative cell proliferation in the established target organs (liver, kidneys, and nasal passages) of female F-344 rats given chloroform daily by gavage. Rats were administered chloroform dissolved in corn oil at doses of 0, 34, 100, 200 or 400 mg/kg/day for 4 consecutive days or for 5 days/wk for 3 wk. Bromodeoxyuridine (BrdU) was administered through an implanted osmotic pump 3.5 days prior to autopsy to label cells in S-phase. Cells in S-phase were visualized immunohistochemically in tissue sections and the labelling index (LI) calculated as the percentage of cells in S-phase. Mild degenerative centrilobular changes and dose-dependent increases in the hepatocyte LI were observed after administration of 100 mg or more chloroform/kg/day. Rats given 200 or 400 mg/kg/day for 4 days or 3 wk had degeneration and necrosis of the proximal tubules of the renal cortex. Regenerating epithelium lining proximal tubules was seen histologically and as an increase in LI. Dose-dependent increases in LI were observed in the kidneys at doses of 100 mg or more chloroform/kg/day at both 4 days and 3 wk. Two distinct treatment-induced responses were observed in specific regions of the olfactory mucosa lining the ethmoid region of the nose. A peripheral lesion was seen at all doses used and included new bone formation, periosteal hypercellularity and increased cell replication. A central lesion was seen at doses of 100 mg or more chloroform/kg/day and was characterized by degeneration of the olfactory epithelium and superficial Bowman's glands. These observations define the dose-response relationships for the liver, kidneys and nasal passages as target organs for chloroform administered by gavage in the female F-344 rat. PMID- 7797173 TI - Toxicological consequences of aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 2. Reproduction and infant findings. AB - A group of 80 menstruating rhesus (Macaca mulatta) monkeys were randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated within each room to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of continuous dosing, approximately 90% of the treated females had attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Commencing on test month 37, each female was paired with an untreated male until either an impregnation occurred or the 29-month breeding phase of the study was completed. The females continued to receive their daily test dose during mating and gestation. To preclude an infant ingesting the mother's dosing capsule, dosing of the dam was discontinued when a nursing infant was approximately 7 wk old. Treatment was restarted when the infant was weaned at 22 wk of age. At parturition, and every 4 wk until weaning, milk and blood samples were obtained from the dam and a blood sample was obtained from the infant for PCB analysis. When the infant was 20 wk old, immunological testing was initiated and an adipose sample was obtained from the infant and dam for PCB analysis. Subsequently, further adipose and blood samples were obtained from the infant and blood specimens were obtained from the dam for PCB analysis. Concurrently, each infant was subjected to anthropometric measurements and detailed clinical examinations until it was approximately 122 wk old. At 122 wk some of the control and all of the treated infants were killed humanely and autopsied. A statistical analysis of the reproduction data provided evidence for a significant decreasing dose-related trend in conception rates and a significant increasing dose-related trend in foetal mortality. Several comparisons between impregnated and non-impregnated females did not implicate 'age' as a confounding factor regarding these results. The major findings with the infants involved some immunological test differences and mild clinical manifestations of PCB ingestion. PMID- 7797174 TI - Migration of styrene from polystyrene foam food-contact articles. AB - Polystyrene foam is used in many food-contact articles such as plates, cups, bowls, egg cartons, meat trays and hinged 'carryout' containers. In most of these applications the food is in contact with the article for a relatively short period of time at mild temperatures (up to 130 degrees F), or for longer periods of time at refrigerated temperatures (40 degrees F). The extent of migration of residual styrene from foam articles under these conditions is of interest in order to predict potential exposure of consumers to styrene from food-contact polymers. Studies of styrene migration from all polystyrene foam articles except egg cartons were completed using food oil as the simulant. Results showed that the amount of styrene migrating from the various food-contact articles made with thermoformed polystyrene sheet into food oil was proportional to the square root of time of exposure. The mean diffusion coefficients derived from these data, assuming the migration was Fickian in nature, showed a linear relationship between the log of the diffusion coefficient and the inverse of the absolute temperature of exposure from 70 to 150 degrees F (21-66 degrees C). The mean diffusion coefficients ranged from about 4.5E-11 cm2/s at 70 degrees F to 3.4E-9 cm2/s at 150 degrees F. Among the four thermoformed articles exposed to food oil, the diffusion coefficients varied by a factor of four or less at a given temperature. The migration of styrene from egg cartons was examined using conditions simulating 'typical' exposure temperature and time with 8% ethanol as the simulant (31 days at 40 degrees F (4 degrees C)). No migration of styrene was observed under this condition, with a detection limit of < 0.01 micrograms/cm2. PMID- 7797175 TI - Acute and subchronic toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b). AB - The acute and subchronic toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b), a CFC alternative, was evaluated in several acute and subchronic studies to assist in establishing proper handling guides. Data from acute toxicity studies in rats and rabbits demonstrated that HCFC-141b has very low acute toxicity. HCFC-141b was not a skin irritant, but was a mild eye irritant, in rabbits and was not a skin sensitizer in guinea pigs. Skin application of HCFC-141b to rabbits at 2000 mg/kg body weight produced no adverse effects. Oral administration at 5000 mg/kg body weight did not cause any deaths or clinical signs of toxicity in rats. The 4 hr LC50 for HCFC-141b was about 62,000 ppm in rats. Repeated exposures of rats for 6 hr/day, 5 days/wk for up to 90 days at concentrations of 2000, 8000 or 20,000 ppm did not result in significant adverse effects. Minor, but dose dependent, reductions in body weight were observed in male and female rats during the 90-day study. Decreased responsiveness was also observed in rats but only at 20,000 ppm. An increase in serum cholesterol or triglycerides was observed in male and female rats at 20,000 ppm, and in males at 8000 ppm. No specific organ pathology was noted in these subchronic inhalation studies. The no-observable adverse-effect level (NOAEL) from these studies was 8000 ppm. Results from other studies demonstrate that HCFC-141b was not neurotoxic in rats. As with trichlorofluoroethane (CFC-11), a cardiac sensitization response to an intravenous epinephrine challenge occurred in dogs with HCFC-141b at 5000 ppm and higher concentrations in experimental screening studies. PMID- 7797176 TI - Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1 dichloro-1-fluoroethane (HCFC-141b). AB - A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects. PMID- 7797177 TI - Genotoxic effects of two industrial effluents and ethyl methane sulfonate in Clarias lazera. AB - The genotoxic effects of industrial effluents from a brewery and a textile mill and of ethyl methane sulfonate (EMS) were investigated by the micronucleus test in Clarias lazera, a tropical freshwater fish. Fish obtained from a local market were kept in laboratory aquaria for 3 wk and then exposed to different concentrations (0.5 to 8 mg/litre) of EMS or brewery or textile-mill effluent (10 60%, v/v) for 14 days. The frequency of micronucleated erythrocytes was determined from blood smears and the results were analysed by linear regression and variance analysis. Exposure to EMS or effluent resulted in statistically significant increases in micronucleus frequency and there was a positive dose response effect over the entire dose range. The textile-mill effluent dose response curve was significantly higher than that of the brewery effluent. The suitability of the micronucleus test in fish for the screening of aquatic genotoxicants is highlighted and the importance of intensified monitoring of the aquatic environment is emphasized. PMID- 7797178 TI - Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid. AB - The dermal response of three strains of mice (ICR, C3H and B6C3F1) exposed to repeated doses of 0, 1 or 4% acrylic acid was examined over 13 wk. Microscopic and gross changes to the skin were classified as being indicative of exceeding the maximum tolerated dose (MTD), reaching the MTD, or tolerating the dose based on proposed MTD guidelines established in US Environmental Protection Agency (EPA) Workshops on dermal carcinogenesis bioassays. A significant number of animals in all three strains with repeated exposure to 4% acrylic acid experienced skin irritation that was classified as having reached or exceeded the MTD compared with animals exposed to either 1% acrylic acid or the 0% acrylic acid acetone control. These results were observed within the first 3 wk of exposure, but there was some accommodation to irritation by 8 wk of exposure. Microscopic findings provided a more sensitive index for exceeding MTD than gross observations taken only at autopsy, but generally correlated well for MTD if gross observations were taken at regular intervals during treatment. That is, to set MTD, gross observations could be used if taken over the entire course of the exposure, but using microscopic findings was generally a more reliable or sensitive measure. EPA guidelines suggest that it is inappropriate to conduct a dermal bioassay at concentrations that exceed the MTD. Acrylic acid at 4% in acetone clearly exceeded the MTD based on microscopic or gross observation criteria. At 4%, strain differences were evident by gross observation only, with the ICR strain being less susceptible to irritation than C3H or B6C3F1 strains. These strain differences were not apparent with microscopic examination. Acrylic acid at 1% in acetone, although demonstrating signs of minimal irritation, was fairly well tolerated by all mice in all strains. Thus, acrylic acid at 1% in acetone, one-quarter of the concentration that was in clear excess of the MTD, would be the appropriate dose concentration for lifetime skin studies based on MTD criteria. PMID- 7797179 TI - The safety and regulatory status of food, drug and cosmetics colour additives exempt from certification. AB - Colour additives exempt from certification (also known as 'natural colour additives') are commonly used in the United States to colour foods, drugs and cosmetics. The US Food and Drug Administration established regulations governing the use of these colour additives, and the labelling of the products that contain them. The safety of these colour additives has been demonstrated by safety testing programs that have yielded a significant amount of toxicology data, and also by a long and well documented history of safe use in the United States and elsewhere. In this report we review the data supporting the safety of the colour additives that are exempt from certification and approved for use in the USA, and conclude that the safety of these colour additives is well supported by the available data. Relevant aspects of the regulation of these colour additives are also described. PMID- 7797180 TI - Multiple linear regression analysis of hypertrophy, calcium and cadmium in hypertensive and non-hypertensive states. AB - Heart disease remains a major public health issue. In this study we aimed to achieve a greater mathematical and mechanistic understanding of the relationship between exposure to heavy metals and heart disease. Measurements of calcium and cadmium levels were made by flame atomic absorption spectrophotometry in tissue from hypertensive and non-hypertensive rabbits. Relationships between hypertrophy, calcium and cadmium were tested using multiple regression analysis. Multiple linear relationships occurred that showed the dependence of hypertrophy on calcium and cadmium levels, and of calcium accumulation on cadmium and hypertrophy. These data provide an insight into the mechanisms of heavy metal accumulation and the development of cardiovascular hypertrophy. PMID- 7797181 TI - Bioactive organosulfur phytochemicals in Brassica oleracea vegetables--a review. AB - Sulfur-containing phytochemicals of two different kinds are present in all Brassica oleracea (Cruciferae) vegetables (cabbage, broccoli, etc.). They are glucosinolates (previously called thioglucosides) and S-methyl cysteine sulfoxide. These compounds, which are derived in plant tissue by amino acid biosynthesis, show quite different toxicological effects and appear to possess anticarcinogenic properties. Glucosinolates have been extensively studied since the mid-nineteenth century. They are present in plant foods besides Brassica vegetables with especially high levels in a number of seed meals fed to livestock. About 100 different kinds of glucosinolates are known to exist in the plant kingdom, but only about 10 are present in Brassica. The first toxic effects of isothiocyanates and other hydrolytic products from glucosinolates that were identified were goitre and a general inhibition of iodine uptake by the thyroid. Numerous studies have indicated that the hydrolytic products of at least three glucosinolates, 4-methyl-sulfinylbutyl (glucoraphanin), 2-phenylethyl (gluconasturtiin) and 3-indolylmethyl (glucobrassicin), have anticarcinogenic activity. Indole-3-carbinol, a metabolite of glucobrassicin, has shown inhibitory effects in studies of human breast and ovarian cancers. Kale poisoning, or a severe haemolytic anaemia, was discovered in cattle in Europe in the 1930s, but its link with the hydrolytic product of S-methyl cysteine sulfoxide was only shown about 35 years later. S-methyl cysteine sulfoxide and its metabolite methyl methane thiosulfinate were shown to inhibit chemically-induced genotoxicity in mice. Thus, the cancer chemopreventive effects of Brassica vegetables that have been shown in human and animal studies may be due to the presence of both types of sulfur-containing phytochemicals (i.e. certain glucosinolates and S-methyl cysteine sulfoxide). PMID- 7797182 TI - A new surgical method from the viewpoint of personal identification: a case of identification based on the presence of a metallic Z-stent. AB - To the best of our knowledge, the first case of successful personal identification based on the characteristic finding of a metallic Z-stent, unexpectedly discovered in the common bile duct, is reported. An unknown human male cadaver was found at the seaside. The age was estimated to be approximately 50-70 years and the postmortem interval was considered to be approximately 2 weeks. There was a small surgical scar of 1.5 cm in diameter in the epigastrium. The cadaver was group A in the ABO blood group system. Internally, the following severe injuries were observed: the dislocation of the occipito-atlantal joint, fractures of the cervical and thoracic portions of the spinal column, multiple fractures of the bilateral ribs, and ruptures of the spleen, left kidney and liver. Furthermore, a 4.5 cm long metallic stent was found in the common bile duct, and the gallbladder was not thoroughly identified because of the severely tight adhesion of the surrounding tissues. In every cut surface of the liver, multiple bile plaques, signifying the presence of long-standing cholestasis, were conspicuous. A microscopic examination revealed the invasion of cancer cells into the liver, which was diagnosed as well or moderately differentiated adenocarcinoma, although the primary origin of the adenocarcinoma could not be determined. The cause of his death was diagnosed as traumatic shock. According to the police investigation after the autopsy, it was revealed that a 60-year-old male, suffering from gallbladder carcinoma, had disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797183 TI - A fatal case of drug-induced multi-organ damage in a patient with Hansen's disease: dapsone syndrome or rifampicin toxicity? AB - An elderly patient with borderline tuberculoid Hansen's disease (leprosy) developed the diaminodiphenylsulphone syndrome after approximately 8 weeks of multi-drug therapy comprising dapsone and rifampicin. Postmortem histological examination, following autopsy, demonstrated features consistent with drug induced hepatitis, tubulo-interstitial nephritis and myocarditis. Although these could have been engendered by dapsone toxicity, it was thought that a concommitant adverse reaction to rifampicin, which is known to be hepatotoxic, nephrotoxic and possibly capable of predisposing to the dapsone syndrome, could not be excluded. PMID- 7797184 TI - Iatrogenically-related, fatal haemorrhage occurring in end-stage renal failure: a series of three cases. AB - Three patients with end-stage renal failure died from acute haemorrhage which, in the first two cases, was related to the use of internal jugular catheters for haemodialysis. In the third instance, severe haemorrhage was caused by the apparent self-insertion of a 16-gauge butterfly needle, connected to a siliconised cannula (also designed for haemodialysis) into the superficial median cubital vein of the left forearm. The hazards associated with the use of internal jugular catheters and the medicolegal implications of these cases are briefly discussed. PMID- 7797185 TI - Sudden death arising from a congenital coronary artery fistula. AB - A medico-legal autopsy conducted on a young Chinese man, a victim of sudden unexpected death, with a vague and unconfirmed history of congenital cardiovascular disease, revealed the presence of a congenital right coronary artery (arteriosystemic) fistula communicating with the markedly hypertrophied left ventricle, which showed microscopic evidence of myocardial ischaemia. The pathology of this rare condition is described and briefly reviewed. PMID- 7797186 TI - An unusual case of pneumatically-induced facial and cervical injuries. AB - An army mechanic sustained a penetrating mandibular injury, associated with right atlantooccipital dislocation, when the inner tube of a military truck tyre burst. It is thought that he had used a sledgehammer, having wielded it lengthwise with the free end of its hollow cylindrical handle held uppermost, to reposition the locking ring of the fully inflated tyre. In all probability, the sudden release of highly pressurised air disloged the locking ring and forced the circular end of the handle into his right lower jaw, thereby fracturing the mandible and causing an acute hyperextension injury of the cervical spine, with resultant profound spinal shock and instantaneous death. PMID- 7797187 TI - Accidental death by nitrous oxide inhalation. AB - Nitrous oxide is a popular inhalation anesthetic-analgesic agent. Its euphoric action and its availability have led to its abuse. We report a case of fatal accidental asphyxia due to nitrous oxide abuse. The deceased was a hospital worker who had access to the hospital supply of nitrous oxide. His death was due to hypoxemia and asphyxiation, secondary to nitrous oxide inhalation. PMID- 7797188 TI - Ingestion of lye. AB - This paper reports on the case of a 13-year-old white male who committed suicide by ingestion of heavy duty drain and sewer opener. He left behind a note indicating his suicide. This teenager was grieving over the suicide of one of his friends and was under counseling by a mental health therapist at school. Results of autopsy and toxicological analyses indicated the ingestion of a highly alkaline substance that is consistent with the ingredients of the drain opener mentioned. PMID- 7797189 TI - Vitreous humor alcohol. PMID- 7797190 TI - Vitreous alcohol. PMID- 7797191 TI - Psychiatric morbidity among Finnish prisoners with special reference to socio demographic factors: results of the Health Survey of Finnish Prisoners (Wattu Project). AB - The present study is part of the Health Survey of Finnish Prisoners (Wattu Project). The project dealt with a sample of 1099 Finnish prisoners, of which 82% participated in the study. Because of the representativeness of the sample the results can be generalized to all Finnish prisoners. The methods used consisted of questionnaires, interviews, a clinical examination by prison physicians and gathering of register data. The total prevalence rate of psychiatric cases was 56%. This is much higher than the rate for the Finnish population in general. The high number of mental disorders was due to alcoholism (43%) and personality disorders (18%). These disorders became even more prevalent as the number of prison sentences increased. There was no difference between the prisoners and the general population in the prevalence of psychoses and neuroses. Alcoholism is the most important mental disorder in Finnish prisoners, while drug abuse is rarely found among them in comparison to prisoners in many other countries. PMID- 7797193 TI - Current awareness in hematological oncology. PMID- 7797192 TI - Simultaneous determination of opiates, cocaine and major metabolites of cocaine in human hair by gas chromotography/mass spectrometry (GC/MS). AB - A procedure is presented for the simultaneous identification and quantification of morphine (MOR), codeine (COD), ethylmorphine (EM), 6-monoacetylmorphine (6 MAM), cocaine (COC), benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE), contained in the hair of opiates and cocaine addicts. The method involves decontamination in dichloromethane, pulverization in a ball mill, heat-acid hydrolysis, addition of deuterated internal standards, liquid-liquid extraction and gas chromatography/mass spectrometry (GC/MS) after silylation. The limit of detection (LOD) was approximately 0.1-0.8 ng/mg for each drug, using a 30-mg hair sample. The method is reproductible, with a coefficient of variation (CV) of approximately 8-17%. Cocaine and 6-monoacetylmorphine were the major compounds detected in cases of cocaine (14 cases) and heroin (68 cases) intake. Concentrations were in the range 0.4-78.4 ng/mg (COC), 0.0-36.3 ng/mg (BZE), 0.0 1.6 ng/mg (EME), 0.0-2.1 ng/mg (CE), 0.0-84.3 ng/mg (6-MAM), 0.2-27.1 ng/mg (MOR) and 0.1-19.6 ng/mg (COD). An application in forensic sciences, involving multi sectional analysis, is given. PMID- 7797194 TI - Simultaneous presentation of hairy cell leukemia and follicular small cleaved cell lymphoma in a patient with previous diagnosis of renal cell carcinoma. AB - Hairy cell leukemia is a lymphoproliferative disorder of the B lymphoid system that is associated with an increased incidence of second malignancies. Most of these second neoplasma have been solid tumours and few reports of lymphoid malignancies exist. We report here a case of simultaneous presentation of hairy cell leukemia diagnosed in the spleen of a patient under therapy for follicular lymphoma who had an antecedent history of renal cell carcinoma. The hairy cell leukemia and the follicular lymphoma were studied by means of molecular techniques and they were found to contain two different clonal B cell proliferations. This suggests an independent origin of these two B cell neoplasms. As far as we know, this is the first report of the coexistence of hairy cell leukemia and follicular lymphoma. PMID- 7797195 TI - Multiple myeloma: an immunoclinical study of disease and response to treatment. AB - Plasma cytokines and immune markers were assessed during the clinical management of 42 patients with multiple myeloma, MM. Of the patients 22/42 (all with progressive disease) were studied from the time of diagnosis, through various treatment regimes, to remission, progression or death. 5/42 patients had monoclonal gammopathy of undetermined significance (MGUS), 8/42 others had either indolent MM or stable MM, and a further 7/42 with progressive disease were also studied. IL-6, TNF-alpha, IL-1 alpha, IL-1 beta, beta 2 microglobulin (beta 2M), and neopterin were estimated in bloods taken under optimal conditions for cytokine detection. The levels were compared with a panel of samples from healthy volunteers. Both immunoreactive and biologically active plasma IL-6 levels were measured. Pretreatment IL-6 levels (both immunoreactive and biologically active) were found to correlate with severity of disease. In 13/22 patients with progressive disease who had been followed from the time of diagnosis over a 12 month period or until death, pretreatment IL-6 levels were predictive of response to therapy. Elevated plasma levels of TNF-alpha, beta 2M and neopterin were found in patients with progressive multiple myeloma, and this correlated with renal impairment. The analytes measured during the course of chemotherapy did not show correlation with disease progression or response to therapy. PMID- 7797197 TI - High grade non-Hodgkins lymphoma in the elderly--12 year experience in the Grampian Region of Scotland. AB - A retrospective examination of patients with high grade non-Hodgkin's lymphoma (HG NHL) presenting in the Grampian Region of Scotland from 1980-1992 was undertaken to determine the disease characteristics and outcome in patients over the age of 60 years at diagnosis. This group of patients was found to account for 68 per cent of HG NHL presenting in this region. No difference in clinical stage or histology was noted compared to their younger counterparts. The elderly had a significantly poorer survival with an increase in lymphoma-related and unrelated deaths. On Cox regression analysis the main survival advantage was conferred by completion of 'radical' treatment; elderly patients who were given 'radical' therapy had a median survival of 50 months compared to median survival of 10 months in the 'non-radical' group. Patients who had a good performance status at diagnosis had also a significant survival advantage. Histology, clinical stage at diagnosis and age over 60 had no independent significant effect on survival. Not all the factors that resulted in 'non-radical' therapy being given are explicable but we conclude that 'radical' therapy is achievable in 50 per cent of patients over the age of 60 years with an effective outcome and should be pursued in the elderly when the condition of the patient allows. PMID- 7797198 TI - The polymerase chain reaction in histopathology. AB - Thanks to the advent of the polymerase chain reaction (PCR) molecular genetic study of histological samples is now a relatively straightforward task and the vast histopathology archives are now open to molecular analysis. In this review we outline technical aspects of PCR analysis of histological material and evaluate its application to the diagnosis and study of genetic, infectious and neoplastic disease. In addition, we describe a number of newly developed methods for the correlation of PCR analysis with histology, which will aid the understanding of the molecular basis of pathological processes. PMID- 7797196 TI - Hepatosinusoidal leukaemia/lymphoma consisting of Epstein-Barr virus-containing natural killer cell leukaemia/lymphoma and T-cell lymphoma; mimicking malignant histiocytosis. AB - Previously diagnosed cases of hepatosinusoidal T-cell lymphoma and malignant histiocytosis (MH) may include lymphoid neoplasms of natural killer (NK) cell lineage associated with Epstein-Barr virus (EBV). Such hepatosinusoidal neoplasms were found to demonstrate hepatomegaly but not lymphadenopathy, and all were diagnosed by a liver biopsy. Sixteen adult patients diagnosed with hepatosinusoidal leukaemia/lymphoma (six NK-cell leukaemia/lymphomas [NKLLs], five instances of MH, three T-cell malignant lymphomas [T-MLs], and two adult T cell leukaemia/lymphomas [ATLLs] were examined for EBV by in situ hybridization, then were studied immunohistochemically and subjected to a DNA analysis. Among our five patients with MH, neoplastic cells showed T-cells, but no histiocytic markers, and they were considered to have either a T-cell or NK-cell lineage. All NKLLs, MHs and T-MLs, except for ATLLs accompanied by reactive hemophagocytic histiocytes, varied in number in each case. In situ hybridization revealed the presence of EBV in the nuclei of atypical cells in all of the six lymphoid neoplasms of NK-cell lineage. Each case of MH and each T-ML which represented EBV demonstrated no definite T-cell or histiocytic markers. Patients with ATLL did not reveal EBV. In all patients with hemophagocytosis, EBV was present in the nuclei of the neoplastic lymphocytes, but not in the hemophagocytic cells. Finally, the 16 cases were reclassified into eight cases with EBV-containing NKLLs, six T-MLs, and two ATLLs. In addition, no true histiocytic neoplasms were observed. The mechanism of hemophagocytosis may be therefore the production of lymphokines (macrophage-activating factors) by neoplastic lymphocytes. EBV associated hepatosinusoidal leukaemia/lymphoma may thus contain a lymphoid neoplasm of NK-cell lineage, which made it difficult to be distinguished from the previously designated malignant histiocytosis. PMID- 7797199 TI - Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in unicystic ameloblastoma. AB - The expression of proliferating cell nuclear antigen (PCNA) and Ki-67 was studied in unicystic and solid ameloblastoma (follicular and plexiform types) using a biotin-streptavidin method on routinely processed paraffin sections. To determine percentage PCNA and Ki-67 labelling indices, positive tumour cells and total tumour cells were counted in areas of each unicystic ameloblastoma corresponding to cystic linings, intraluminal nodules and invading tumour islands, and in solid ameloblastomas. Positive cells in basal and suprabasal layers of cystic tumour lining were also counted with respect to the length of basement membrane determined by image analysis. In unicystic ameloblastoma the invading islands exhibited a significantly higher PCNA labelling index (29.2 +/- 16.4%) than intraluminal nodules (13.6 +/- 5.4%; P < 0.05). Cystic tumour lining had relatively few PCNA positive cells and a labelling index (5.5 +/- 3.3%) significantly lower than invading islands (P < 0.001) or intraluminal nodules (P < 0.003). The labelling indices of solid ameloblastomas of follicular type (48.1 +/- 12.9%) were significantly higher than those of cystic tumour lining (P < 0.0001), intraluminal nodules (P < 0.001) and invading islands (P < 0.04) in unicystic ameloblastoma. Similar relationships were found for Ki-67 expression except that comparisons involving invading islands and intraluminal nodules were not significant, a finding probably due to the smaller number of specimens available for quantitative analysis. These results indicate differences in proliferative potential between different areas of unicystic ameloblastoma and between unicystic and solid lesions. The fact that invading tumour islands within the fibrous tissue wall showed high labelling indices is in agreement with the clinical observation that their presence may be related to recurrence after conservative surgery. This provides a biological basis for indicating more radical surgical excision as the treatment of choice for this subgroup of lesions. PMID- 7797200 TI - Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity. AB - Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle-aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow-up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms. PMID- 7797201 TI - A study of the association of Epstein-Barr virus with Burkitt's lymphoma occurring in a Chinese population. AB - There is a strong association (approximately 95%) of endemic Burkitt's lymphoma with Epstein-Barr virus (EBV), whereas the association is weak for the sporadic form occurring in Western countries (approximately 15%). In the Middle East, North Africa and South America, 60-80% of Burkitt's lymphomas harbour EBV. These epidemiological differences suggest that either the endemicity of EBV or socio economic conditions, or both, may influence the pathogenetic role of EBV in Burkitt's lymphoma. Since only meagre data are available on Asians, this study was performed to address this issue by studying cases from Hong Kong, where EBV seroconversion occurs in the first few years of life but the socio-economic conditions approach those of Western countries. In situ hybridization for EBV encoded RNAs (EBERs) was performed on paraffin sections of 18 cases of Burkitt's lymphoma. Labelling of the neoplastic cells was detected in five cases (27.7%). In contrast, among 54 cases of B-cell lymphomas of various subtypes studied for comparison, signals for EBER were detected in only one case each of T-cell-rich large B-cell lymphoma, anaplastic large cell lymphoma and Reed-Sternberg-like cells occurring in B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma. The strong labelling with oligo-dT probe (which hybridized with the polyadenylated ends of mRNA) in all cases suggested that the negative results were genuine and not due to poor preservation of RNA in the tissues. Thus, among B-cell neoplasms occurring in Chinese, Burkitt's lymphoma shows a statistically stronger association (P < 0.01) with EBV than with other types of B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797202 TI - Primary pulmonary tumours of nerve sheath origin. AB - Primary intrapulmonary tumours of nerve sheath origin are extremely rare. We describe the clinicopathological features of four such peripheral nerve sheath tumours, two benign and two malignant. Of the benign tumours, one was a typical schwannoma and the other an ancient or degenerated schwannoma. The typical schwannoma was endobronchial in origin, diagnosis being established by small bronchoscopic biopsy. The histological diagnosis of malignant peripheral nerve sheath tumour required immunohistochemical and/or ultrastructural evidence of nerve sheath differentiation. One malignant tumour arose in a patient with Von Recklinhausen's disease. Both malignant tumours behaved aggressively with the development of multiple intrapulmonary metastases, despite the markedly different histological appearance of the two tumours. Flow cytometric analysis of nuclear DNA content was performed on the four tumours, all of which showed a diploid DNA profile. PMID- 7797203 TI - Salivary duct carcinoma. AB - Twelve cases of salivary duct carcinoma were examined clinically, pathologically and by flow cytometry to quantify their histological features as well as attempt to identify factors predictive of patient outcome. All of the tumours arose in the parotid gland. Eight of the twelve patients were male. Four patients died of disease (median survival 12.5 months); three are alive with disease; and five are alive with no evidence of disease (mean follow-up of 50 months). Two tumours arose in a pre-existing pleomorphic adenoma. Positive lymph nodes were present in eight of ten patients sampled; patients with two or more positive lymph nodes tended to die of their disease or be alive with metastases. Comedo necrosis, perineural invasion and vascular invasion were common findings by light microscopy. Ten of the twelve tumours were aneuploid. Neither clinical stage, tumour size, aneuploidy nor histological features correlated with patient outcome. This study confirms the aggressive nature of salivary duct carcinoma. PMID- 7797205 TI - Melanotic oncocytic metaplasia of the nasopharynx. AB - Two cases of melanotic oncocytic metaplasia occurring in the nasopharynx are reported. One presented with serous otitis media and the other with tinnitus. Nasoscopic examination revealed a small brown nodule obstructing the Eustachian tube in both cases. While oncocytic metaplasia of the nasopharynx is not too uncommon, melanin pigmentation of the nasal or nasopharyngeal mucosa is very rare. To our knowledge, their combination has not been described. PMID- 7797204 TI - Localized amyloid deposition in cartilage is glycosaminoglycans-associated. AB - Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage-containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan-related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour-like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl2), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies derived from the articular surface. Other cartilaginous lesions (including loose bodies of primary synovial chondromatosis) were negative for amyloid and did not contain highly sulphated glycosaminoglycans. These findings suggest that changes in specific highly sulphated glycosaminoglycans may play a role in localized amyloid deposition in articular cartilage. PMID- 7797206 TI - Cutaneous verruciform xanthoma arising on a congenital lymphoedematous leg. PMID- 7797207 TI - Sclerosing osteosarcoma of the great toe phalanx in an 11-year-old girl. PMID- 7797209 TI - Recurrence of lupus nephritis in a renal allograft with histological transformation of the lesion. PMID- 7797208 TI - Focal myositis of the tongue--a pseudotumoral lesion. PMID- 7797210 TI - Infective endocarditis--recent trends. PMID- 7797212 TI - Ventricular tachycardia with left bundle branch block morphology in the absence of ischaemic heart disease--clinical and electrophysiological observations. AB - Clinical and electrophysiological features of 20 patients presenting with ventricular tachycardia (VT) of left bundle branch block (LBBB) morphology without evidence of coronary artery disease were studied. The mean age of the patients was 35.2 +/- 12 (range 15-57 years). The rate of VT varied between 140 240/min (182 +/- 80). Six (30%) patients experienced giddiness or syncope during palpitations. Structural heart disease was found in 10 (50%) of these patients, which included arrhythmogenic right ventricular dysplasia in five, submitral left ventricular (LV) aneurysm in one, anterolateral LV dyskinesis in one, dilated cardiomyopathy in one, endomyocardial fibrosis in one and nonobstructive hypertrophic cardiomyopathy in one case. Ten patients were free of structural heart disease. Electrophysiological study was done in all patients. VT with same morphology as spontaneous VT was inducible in only 14 patients. Seventeen patients were treated medically with total or partial amelioration of symptoms. In three patients, two with arrhythmogenic right ventricular dysplasia and one with structurally normal heart, who were unresponsive to drug therapy, the VT focus could be mapped in right ventricular outflow tract and successful electrical ablation was done. Thus in patients who present with VT with LBBB morphology, the heart is often structurally normal but organic disease is not uncommon, and should be carefully searched. PMID- 7797211 TI - Idiopathic ventricular tachycardia--characterisation and radiofrequency ablation. AB - Forty patients (14 women and 26 men; mean age 40 +/- 13 years, range 7 to 60) diagnosed to have idiopathic ventricular tachycardia (right ventricular 28, left ventricular 12) underwent electrophysiologic study and radiofrequency catheter ablation. Echocardiography, signal averaging, magnetic resonance imaging and cardiac catheterisation with angiography were used as indicated to rule out identifiable underlying etiologies. Gross localisation of the area of origin of the ventricular tachycardia from the surface electrocardiogram could be made in all cases. Accurate localisation of the site of origin was done by activation mapping and pace mapping. Radiofrequency application was successful in achieving a cure in 34 (85%) patients, with a mean of 8.3 +/- 4.7 energy applications and a fluoroscopy time of 38 +/- 19 minutes. Unsuccessful cases were characterised by wide and slurred QRS complexes during ventricular tachycardia, possibly indicating a deeper intramyocardial or epicardial site of origin of the tachycardia. Radiofrequency ablation appears to be the treatment of choice for symptomatic idiopathic ventricular tachycardia, having a high success and safety rate. PMID- 7797213 TI - Our experience with Palmaz-Schatz coronary stent. AB - Between September 1993 and August 1994 we have implanted Palmaz-Schatz coronary stents in 44 patients. Twenty eight patients presented with stable angina and 16 with unstable angina. Stenting was carried out for denovo, focal lesions in large coronary arteries (n = 27), significant dissection during PTCA with acute threatened closure (n = 9), suboptimal results (n = 5), restenosis after PTCA (n = 2) and saphenous vein graft stenosis (n = 1). Successful delivery of the stent was achieved in 43 cases. Percent diameter stenosis was reduced from 77 +/- 11% to 10 +/- 8% and minimal luminal diameter increased from 1.08 +/- 0.28 mm to 2.92 +/- 0.39 mm. There was 1 death due to left main dissection secondary to guiding catheter trauma in a patient taken up for bail out stenting. Vascular/bleeding complications occurred in 3 patients (6.7%). There was no instance of acute or subacute stent thrombosis. Forty patients are symptom free. Eighteen patients underwent six month angiography. Restenosis (> 50% diameter reduction) was seen in 2 and a new lesion distal to stent occurred in 1 case. All have been successfully redilated. A high rate of successful delivery of the Palmaz-Schatz coronary stent can be achieved in a wide spectrum of patients with very few complications. Long term results are very gratifying and encouraging. PMID- 7797214 TI - Beneficial effects of long-term metoprolol therapy on cardiac haemodynamics in patients with mitral stenosis in sinus rhythm--a randomised clinical trial. AB - We conducted a placebo controlled randomised clinical trial to evaluate the effects of 6 months therapy with metoprolol on resting and exercise haemodynamics in 31 patients with isolated mitral stenosis in sinus rhythm. Twenty six of them (placebo n = 13, metoprolol n = 13) completed the study protocol. Their mean age was 23.1 +/- 7.9 years and the mean mitral valve area was 0.93 +/- 0.25 cm2. The dose of metoprolol ranged between 50-100 mg per day. The primary outcome variables for the study were the resting and exercise mean pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) and the secondary outcome variables consisted of resting and exercise heart rate, mean pulmonary artery pressure (PAP), mean pulmonary vascular resistance (PVR) and clinical improvement on visual analog scale. These outcome variables were assessed blindly. The resting and exercise mean PCWP (mmHg) increased by 9.1 +/- 3.1 and 16.4 +/- 6.4 on placebo and 2.5 +/- 2.1 and -4.6 +/- 2.3 on metoprolol after 6 months therapy. These differences were statistically significant (p < 0.01). The resting and exercise CI (liters/min/m2) decreased by 0.2 +/- 0.1 and 0.1 +/- 0.1 on placebo and 0.3 +/- 0.5 and 0.3 +/- 1.0 on metoprolol. These haemodynamic effects were accompanied with much better symptomatic improvement in patients treated with metoprolol. The differences in change in mean PAP and PVR in two groups were statistically not significant. Our results suggest that the symptomatic patients with MS, waiting for definitive intervention for 6 months or less, would benefit if given beta blockers during this period. PMID- 7797215 TI - Comparative evaluation of left ventricular function in sick sinus syndrome on different long-term pacing modes. AB - Single-chamber ventricular pacing has been implicated in the development or progression of congestive heart failure in patients with sick sinus syndrome (SSS). To define the exact role of pacing modality in causation of congestive heart failure, quantitative two-dimensional echocardiographic examination was performed in 51 consecutive patients with SSS who received an initial pacemaker from January 1979 to September 1989 and were free of any structural heart disease at the time of implant. Atrial or dual chamber pacemakers were implanted in 21 patients (Group I) and ventricular pacemakers in 30 (Group II). The two groups were matched for age, gender, paced rate, blood pressure and duration of pacing. After a mean follow-up of 64 +/- 34 months, congestive heart failure developed in one patient in group I and 3 in Group II. Patients in group II, had larger left atrium (41 +/- 5 vs 37 +/- 6 mm, p < 0.05) and left ventricular end-diastolic volume (64 +/- 18 vs 54 +/- 12 ml/m2, p < 0.01) but similar left ventricular end systolic volume (27 +/- 12 vs 24 +/- 9 ml/m2, p = NS), ejection fraction (59 +/- 10 vs 57 +/- 8%, p = NS), left ventricular mass (84.8 +/- 31 vs 85.6 +/- 29.2 gm/m2, p = NS), meridian end-systolic wall stress (48.3 +/- 22.1 vs 49.8 +/- 25 Kdynes/cm2, p = NS) and wall stress/end-systolic volume ratio (1.27 +/- 0.94 vs 1.42 +/- 0.59, p = NS). Pacing mode does not appear to influence left ventricular systolic function in patients with SSS. PMID- 7797216 TI - Effect of posture in immediate post-exercise period on ischaemic ST-changes during stress electrocardiographic testing. AB - In this study of stress testing, the posture in which patients were put had effect on heart rate, blood pressure, rate pressure product and ST-segment depression integral in the recovery phase. The systolic blood pressure in recovery phase of stress testing fell more rapidly towards normal pre-exercise value in sitting (Group I) than in lying down (Group II) posture (p < 0.05) from 2nd to 5th minute. The changes in heart rate were less and slower in lying posture than with sitting up. The decrease in rate pressure product (RPP), a determinant of myocardial oxygen requirement was lower in lying down than in sitting up posture (p < 0.05) from 2nd to 5th minute of recovery. Consequently, ST-depression, a marker of ischaemia was more marked in lying down than sitting up. The ST-depression integral was 4.15 +/- 1.2 and 7.10 +/- 1.65 in 2nd minute in group I and group II respectively, and the difference was statistically significant in 2nd, 7th (p < 0.05) and 8th minute (p < 0.01) of recovery. These changes are important in interpretation of results of exercise testing. PMID- 7797217 TI - Evaluation of coronary artery disease by dipyridamole echocardiography test. AB - Role of oral dipyridamole echocardiography test (DET) was evaluated in 50 patients with effort angina. All patients underwent coronary angiography, the day after oral DET. The echo studies were performed at rest and 65 +/- 15 minutes after 300 mg of oral dipyridamole. Segmental wall motion was analysed in a 16 segment model and a wall motion score index (WMSI) was generated for the entire left ventricle both at rest and following the drug. WMSI was significantly higher after oral dipyridamole, (p < 0.001) compared to resting condition with increased sensitivity (86% vs 74%). When results of DET were compared with coronary angiography, the correlation of WMSI was statistically significant in three vessel disease (p < 0.001), two vessel disease (p < 0.001) as well as for left anterior descending lesions (p < 0.001). However, it was insignificant for single vessel disease, viz, right coronary artery and circumflex artery. Thus we conclude that oral DET is a safe, inexpensive, sensitive and non-exercise dependent method for demonstrating myocardial ischaemia with high diagnostic accuracy. PMID- 7797218 TI - Profile of coronary risk factors in patients with manifest ischaemia and normal coronary arteries. AB - Risk factor profile of 142 patients with normal epicardial coronary arteries (86 males, 56 females, mean age 47 +/- 11 years) out of 1,508 consecutive patients undergoing coronary angiography was analysed. The mode of presentation in these patients was old or recent myocardial infarction (16.1%), unstable angina (12.0%), angina on effort (43.7%), atypical chest pain (8.5%), and anginal equivalent (19.7%). One or more stress test was positive in the majority (88%) of patients. Though the majority (39.5%) of patients had one risk factor, multiple (two or more) risk factors were not uncommon. Risk factor profile in patients with normal coronaries included hypertension (45.7%), dyslipidemia (33.8%), obesity (19.7%), positive family history of coronary artery disease (18.3%), cigarette smoking (16.1%), and minor risk factors (hyperuricemia, sedentary life style, Type A personality, oral contraceptive intake -15.4%). The mechanism of myocardial ischemia in patients with normal coronary arteries is not fully understood. We conclude that approximately one tenth of patients with clinically manifest coronary artery disease and one or more conventional risk factors do not have atherosclerotic changes in their epicardial coronary arteries as seen on coronary angiography. PMID- 7797219 TI - Epidemiology of coronary heart disease in a rural Punjab population--prevalence and correlation with various risk factors. AB - An epidemiological study to find out the prevalence of coronary heart disease (CHD) and the influence of risk factors on the prevalence of CHD in a total rural community of Punjab was conducted in Pohir, situated near Ludhiana. A total of 1100 individuals (623 males and 477 females) out of a possible 1617 individuals (> 30 yrs) living in 3 villages were studied. In each case a detailed history, physical examination and a 12 lead electrocardiogram (ECG) were recorded. Samples for blood sugar and serum cholesterol were taken. By Epstein's criteria of ECG (using the Minnesota coding), the prevalence of CHD was 30.8/1000, being higher in women (37.7/1000) than in men (25.6/1000). By a clinical judgement method considering history, ECG and treadmill testing (TMT) collectively, prevalence was 31.8/1000, being still higher in women (33.5/1000) than in men (30.5/1000). The prevalence of various risk factors like hypertension, smoking, hypercholesterolemia and diabetes was found to be 14.5%, 8.9%, 7.0% and 4.6% respectively. Of the various risk factors tested, hypertension, hypercholesterolemia and a positive family history showed an association with CHD. Only 38% of patients with CHD, 37% of the hypertensives and 52% of the diabetics were aware of its presence. The knowledge in the general population about risk factors causing CHD is poor. PMID- 7797220 TI - What is 'desirable' lipid profile. AB - The lipid profile of subjects with and without coronary heart disease (CHD) was studied in two epidemiological studies conducted in an urban and rural population. The prevalence of CHD was 96.7/1000 in the urban area and 27.1/1000 in the rural area. The lipid levels of the rural population, with an entirely different life style, was significantly lower compared to the urban normal population. The data suggest that if the prevalence of CHD is to be reduced in the urban population, the desirable levels of lipids should be those obtained in the rural normal population rather than the urban, CHD free, population. PMID- 7797221 TI - Ultrastructural and histological study of endomyocardial biopsies from patients of dilated cardiomyopathy--a comparative evaluation and their clinical correlation. AB - Morphological studies of dilated cardiomyopathy reveal nonspecific light and electron microscopic features. This study was designed to perform a comprehensive qualitative and semi-quantitative evaluation of histological and ultrastructural parameters in endomyocardial biopsies in 20 cases of DCM. Semi-quantitation of parameters increases the accuracy and precision of evaluation by reducing interobserver variation in assessment. The semi-quantitative score ratios in our study were further correlated with the clinical and hemodynamic data to identify parameter(s) of prognostic significance. In the histological evaluation, myofibre hypertrophy appeared to be the most frequent (95%) and severely affected parameter followed by myocardial degeneration (70%). The ultrastructural features were more diffuse, impressive and severely altered. The most prominent features were mitochondrial degeneration and myofibrillar lysis seen in 100% of our cases. Severe mitochondrial degeneration appeared to be an indicator of poor prognosis in DCM as it was seen in patients with the lowest left ventricular ejection fraction obtained angiographically. Moreover, unlike the light microscopic evaluation, ultrastructural score ratios correlated significantly with the ejection fraction. PMID- 7797222 TI - Coronary artery reoperations using arterial conduits: immediate and early results. AB - This study deals with results of coronary artery reoperations in 21 males aged 54.4 +/- 6.6 years. Native vessel coronary disease at first and second operation was nearly the same (2.7 +/- 0.6 vs 2.8 +/- 0.4 vessel, p = NS). Graft attrition and deterioration in left ventricular ejection fraction (55.9 +/- 9.2 initial vs 36 +/- 15 at reoperation, p < 0.001) necessitated reoperation in majority. Recurrence of angina (71%) and left ventricular failure (23.8%) were the clinical indicators for reoperation. Procedure was successful in 20 (95%) and had to be abandoned in 1 due to severe pericardial and sternal adhesions. Arterial grafts were utilised in 90% (18 cases, Group A and B). Total arterial revascularisation (Group A) was done in 9 (45%) using Y graft 6, combination of both mammary arteries 2, and by both mammary and inferior epigastric artery in 1. Group B patients had arterial grafts (bilateral IMA 1, Y graft 1, bilateral IMA + gastroepipolic 1, RIMA 4, and LIMA 2) in addition to a venous graft. Two patients (group C, 10%) had only venous grafts. There was no in hospital mortality or morbidity and at 10 +/- 5.2 months follow up, all are asymptomatic with negative stress test at 3 months followup in 8 cases. We conclude that coronary artery reoperations using arterial conduits can be performed safely with excellent immediate and early results. PMID- 7797223 TI - Use of aspirin as the sole antiplatelet agent following prosthetic valve replacement in rheumatic heart disease. AB - Aspirin was administered as the sole antiplatelet agent in 147 patients following valve replacement, who were at low risk for thromboembolism. Of these, 67 underwent mitral valve replacement (MVR), 61 aortic valve replacement (AVR) and 19 combined aortic and mitral valve replacement (DVR). The mean follow up period was 6.63 years (range 1-14 years). The incidence of thromboembolic episodes (TEE) in patients following MVR, AVR, and DVR was 0.41, 0.80 and nil respectively. The TEE free survival at the first year follow-up was 98.4%, 99.3% and 100% in patients following MVR, AVR and DVR respectively. Fatal intracranial haemorrhage was not encountered. Valve thrombosis in this patient population was not seen. In conclusion, aspirin as the sole antiplatelet agent appears to be safe and effective following prosthetic valve replacement in selected patients. Further studies involving larger number of patients are necessary to confirm these results. PMID- 7797225 TI - Percutaneous closure of patent ductus arteriosus with coil. PMID- 7797226 TI - A rare combination of Marfan's syndrome, rheumatic heart disease and muscular dystrophy--a case report. PMID- 7797227 TI - Situs inversus with dextrocardia with corrected transposition of great vessels with rheumatic systemic atrio-ventricular valve regurgitation: a 63 year old adult survivor. PMID- 7797224 TI - Alteration in pulmonary mechanics after coronary artery bypass surgery: comparison using internal mammary artery and saphenous vein grafts. AB - Pulmonary function tests, arterial blood gas tensions and morbidity were compared in 50 patients undergoing coronary artery bypass graft surgery. Thirty patients had bilateral internal mammary grafts (Group 1), 5 patients had only saphenous vein grafts (Group 2) and 15 patients had a single arterial graft in addition to vein grafts (Group 3). Pleural effusion and wound infection were more common in patients with internal mammary artery grafts (p < 0.05). Patients in Group 2 required prolonged ventilation but this could be related to their underlying left ventricular dysfunction. Patients in all the three groups developed a severe restrictive ventilatory defect in the postoperative period and the degree of impairment was maximum in Group 1 patients (p < 0.01). These patients also had evidence of small airway obstruction. Thus an overall decrease in pulmonary function occurs in the postoperative period by 30 to 40% (p < 0.001). The derangement is greater in patients with arterial grafts, as a result of impaired blood supply, increase in pleural drains and additional surgical trauma secondary to mobilization of internal mammary arteries leading to delayed recovery. The awareness of these findings can be of great value in postoperative management of these patients. In addition, these observations should also be kept in mind while planning the choice of grafts in a patient undergoing coronary artery bypass graft surgery. PMID- 7797228 TI - Omentopexy in limb revascularisation in Buerger's disease. PMID- 7797229 TI - "Over the wire Inoue technique". PMID- 7797230 TI - Ehrlich and Darwin: homochauvinism in immunology. PMID- 7797232 TI - Humoral immune responses to systemic Candida albicans infection in inbred mouse strains. AB - The protective role of humoral antibodies in the resolution of systemic candidiasis remains controversial. Investigation of the humoral immune responses in mouse strains of varying susceptibility to infection may demonstrate a link between mouse strain susceptibility, antibody production and specificity, and the ability to resolve an infection. The antibody response in five different strains of mice during primary immune response to systemic infection with Candida albicans was investigated. Immune sera were fractionated by protein A affinity chromatography to yield fractions containing IgG1, IgG2a and IgG2b immunoglobulins. BALB/c mice of low susceptibility to the infection and DBA/2J mice of high susceptibility produced increased levels of the IgG1 isotype and decreased levels of the IgG2a isotype. AKR, CBA/H and C57B1/6J mice of moderate susceptibility produced antibodies predominantly of the IgG2a isotype. The patterns of antigen recognition by antibodies in immune sera and in fractions obtained after protein A chromatography of immune sera were investigated by western blotting and immunostaining. Antibodies from AKR(H-2K) and CBA/H (H-2k) mice reacted strongly after immunoblotting with antigens of 87 and 96 kDa. In contrast, immune sera from both the highly susceptible DBA/2J (H-2d) mice and the resistant BALB/c (H-2d) mice reacted strongly with an antigen of 48 kDa. C57B1/6J (H-2b) mice produced variable antibody reactivity to antigens of 48, 65, 66 and 79 kDa depending on the IgG subclass tested. The IgG subclass responses and the patterns of antigen recognition in these mice suggest that humoral responses to C. albicans may be restricted by H-2 haplotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797231 TI - Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: evidence for cytokine dependence and detection of a novel sulfatase. AB - The subendothelial basement membrane (BM) is regarded as an important barrier to the entry of leucocytes into inflammatory sites. This study compares the ability of leucocytes, platelets and endothelial cells (EC) to degrade a [35SO4]-labelled subendothelial extracellular matrix (ECM) and assesses the effect of PMA and various pro-inflammatory cytokines on this degradative activity. The different products of degradation, identified by fast protein liquid chromatography (FPLC) gel filtration chromatography, were indicative of protease, endoglycosidase (heparanase) and exoglycosidase and/or sulfatase activity. In terms of ECM degradation, EC and platelets were the most active, with PMA stimulation further enhancing the degradative activity of these two cell types. Platelets exhibited predominantly heparanase activity whereas the EC degradation products suggested a range of enzymic activities, namely proteases, heparanases and sulfatases. Interestingly, EC in suspension expressed these three enzymic activities whereas confluent EC monolayers only exhibited sulfatase activity, suggesting that the former situation might represent an angiogenic response. In the case of leucocytes, neutrophils and lymphocytes degraded the ECM to a much greater extent than monocytes. Each cell type also differed in the predominant enzymic activities it expressed, for example, heparanase activity by lymphocytes, protease activity by neutrophils and sulfatase activity by monocytes. Furthermore, PMA stimulation was shown to have differential effects on these enzymic activities. Some pro-inflammatory cytokines were found to be cell-type specific in their effects on ECM degradation. Thus, IL-1 + TNF enhanced neutrophil and EC degradation of the ECM but inhibited lymphocyte ECM degradation. In contrast, the chemokine IL-8 enhanced ECM degradation by neutrophils, lymphocytes and EC. Of particular interest was the unique sulfatase activity expressed by EC and monocytes which was induced in EC by TNF + IL-1 and IL-8, whereas in monocytes the sulfatase activity was exclusively induced by the chemokine monocyte chemotactic and activating factor (MCAF). Collectively, the results of this study show that leucocytes differ markedly in the enzymes they express to degrade the BM during extravasation and that PMA and cytokines are cell-type specific in their induction of hydrolytic enzyme activity. These results also indicate that EC may play an important role, not only in the recruitment of leucocytes, but also via sulfatase activity in the preparation of vascular BM for leucocyte extravasion. PMID- 7797233 TI - Productive in vitro infection of human umbilical vein endothelial cells and three colon carcinoma cell lines with HIV-1. AB - The objective of this study was to assess the ability of HIV-1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV-1 (HIV-1SF2, HIV-1Mck and HIV-1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV inoculated HUVEC secreted elevated levels of IL-6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL-1 beta, TNF-alpha, IFN-alpha and IFN-gamma were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV-1 inoculation. These results confirm that non CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, the production of IL-6 by HIV-infected endothelial cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo. PMID- 7797234 TI - An analysis, using monoclonal antibodies, of the role of interferon-gamma in ovine immune responses. AB - A mAb (IFN-9) which neutralizes biologically active ovine and bovine IFN-gamma was used to deplete levels of the cytokine in vivo in sheep and examine the consequences for immune responses to adjuvanted antigen and skin reactivity to Bacillus-Calmette-Guerin (BCG). Groups of sheep were immunized with ovalbumin in the adjuvants, Quil A or dextran sulphate (MW 500,000; DXS), both of which elicit production of IFN-gamma. MAb anti-IFN-gamma or an isotype control mAb (anti carbonic anhydrase positive particles) were inoculated i.v. during primary and/or secondary responses. Reactions monitored in efferent prefemoral lymph indicated that anti-IFN-gamma effectively depleted levels of IFN-gamma in lymph but had no effects on the magnitude and kinetics of lymphocyte and lymphoblast traffic, or total or isotypic titres of specific Ig. When incubated in vitro with ovalbumin, antigen-reactive cells from anti-IFN-gamma treated sheep did not produce IFN gamma, suggesting an on-going modification to cytokine production. In contrast, skin reactions to purified-protein derivative in sheep immunized with BCG were reduced by < 40% by anti-IFN-gamma. The results indicate that IFN-gamma production may not be obligatory for delayed-type hypersensitivity reactions or for the adjuvant action of Quil A or DXS, and that specific mAb can alter the profile of cytokines produced by antigen-reactive cells in sheep. PMID- 7797236 TI - The trouble with transgenic mice. AB - Observations on many antigen-receptor transgenic models with anti-self specificities have been interpreted as proof for clonal deletion or for mechanisms involved in clonal deletion. At the same time, there is increasing evidence that many lymphocytes that recognize self exist, are activated and produce end products, even in individuals without clinical autoimmunity. Except perhaps for the amount of anti-self activity, there is little agreement on what distinguishes immune products normally recognizing self from those associated with clinical autoimmunity. To resolve this paradox, the tendency in immunology is to accept conclusions from transgenic models as normal, while judging those from the unmanipulated state as suspect. However, transgenics have a major weakness. Transgenes encoding antigen-receptors are derived from highly selected mature lymphocytes and are expressed in developing lymphocytes that normally do not display the antigen-receptors of mature lymphocytes. Such precocious expression of antigen-receptors could have profound abnormal effects on lymphocyte development. Other transgenic models suggest that processes in lymphocyte differentiation not involving antigen-receptor binding specificity exert powerful influences on lymphocyte development; therefore, mechanisms other than classical positive and negative selection are important. PMID- 7797235 TI - The effect of IL-4 on antigen expression: a comparison of fluorescence intensity and antigen density. AB - We have compared the membrane expression of MHC class II antigen and Ig on murine splenic B lymphocytes by two flow cytometric methods. The first method, commonly used, determined the mean immunofluorescence intensity; the second measured antigen density as a ratio of mean fluorescence intensity to cell volume. The data generated by the two methods allow for different interpretations of antigen density in comparison to antigen expression. By mean fluorescence intensity, activated B lymphocytes expressed more MHC class II antigen and membrane Ig than did resting B cells. However, resting B cells had the same density of MHC class II antigen and membrane Ig as activated B cells. Next we examined the effect of IL-4 on antigen expression by the two methods. We found that although IL-4 increased the mean fluorescence intensity and density of MHC class II and membrane Ig on each B cell population, the density of expression of membrane Ig tended to be greater on the resting B cells than on the activated, while the density of MHC class II antigen was essentially the same on each of the IL-4 treated B cell populations. PMID- 7797237 TI - Hypothesis: a memory lymphocyte-specific soma-to-germline genetic feedback loop. AB - Analysis of recently published DNA sequence data obtained for related germline Ig variable (IgV) genetic elements of several vertebrate species revealed the presence of a number of extremely non-random patterns of sequence variability among these genes. Strikingly, the patterns were also observed in two sets of chicken IgV pseudogenes. Since the observed patterns are clearly incompatible with existing theories of multigene family evolution, a new model that can account for all of the data is presented in this paper. The model is a modification and extension of an earlier proposed mechanism whereby somatically expressed genes can be returned to the germline by endogenous retroviruses that may act as soma-to-germline genetic vectors. The mechanism described proposes that the interactions that may result in the soma-to-germline transfer of somatically selected IgV genes occur in the epididymis of the male reproductive tract and are restricted to memory lymphocytes. This mechanism makes a number of predictions that are amenable to experimental testing. From the data presently available in the literature it is not possible to extend the mechanism to the female reproductive tract. PMID- 7797238 TI - Recombinant expression of vaccinia virus-encoded TAP1 and TAP2 promotes MHC class I-restricted antigen presentation in a Syrian hamster cell line. AB - Transporter associated with antigen presentation (TAP) molecules supply small peptides to the lumen of the endoplasmic reticulum for assembly with MHC class I glycoproteins. Here we report that a Syrian hamster cell line, BHK, which is commonly used in cell biological and virological investigations, is deficient in antigen presentation in a xenogeneic model. Thus when the mouse MHC class I restriction element, Kd, is expressed in BHK cells via a vaccinia virus (VV) recombinant, no significant recognition by VV-immune and Kd-restricted cytotoxic T cells is induced. This defect is apparently a consequence of a deficiency in TAP-dependent peptide transport and can be repaired when rat TAP1 and TAP2 are provided by recombinant VV expression. PMID- 7797239 TI - Recognition sites on human IgG for Fc gamma receptors: the role of glycosylation. AB - Human IgG subclass proteins exhibit more than 95% primary amino acid sequence homology in their Fc regions, but each has a unique profile for recognition by the 3 human Fc gamma receptors. The Fc gamma Rs are themselves highly homologous members of the immunoglobulin supergene family. Consistent with these data we have proposed that Fc gamma RI, Fc gamma RII and Fc gamma RIII recognise overlapping non-identical interaction sites in the lower hinge region of the CH2 domain of the IgG molecule. Evidence in support was provided by protein engineering effecting single amino acid replacements in the proposed site. Alternatively, we have demonstrated that the primary amino acid sequence alone is not sufficient for IgG molecules to fold with the generation of Fc gamma R interaction sites and that glycosylation of Asn 297 of the CH2 domain is essential. We have further defined a 'core' oligosaccharide structure that provides for the generation of Fc gamma R interaction sites which suggests that the addition of outer-arm sugar residues does not affect this primary activity; although in vivo it could influence other essential biological activities. These findings have opened up a new approach to engineering antibody function--by protein engineering of amino acid residues that form contacts with the oligosaccharide moiety. In the present report we demonstrate that replacement of contact residues for galactose on the alpha(1-6) arm does not affect Fc gamma RI and Fc gamma RII recognition while replacement of Asp 265, a contact for a 'core' N-acetylglucosamine residue, results in a loss of Fc gamma RI and Fc gamma RII recognition. PMID- 7797240 TI - Regulation of tyrosine-containing activation motif-dependent cell signalling by Fc gamma RII. AB - Crosslinking of the B-cell receptor (BCR) for antigen to low-affinity receptors for IgG (Fc gamma RII) inhibits B-cell activation induced by BCR aggregation. The cell-triggering properties of the BCR depend on tyrosine-containing activation motifs (TAM), in the intracytoplasmic domain of its Ig alpha and Ig beta subunits. TAMs also account for the cell-triggering capabilities of the T-cell receptor (TCR) for antigen, in T lymphocytes, and of the high-affinity receptor for IgE (Fc epsilon RI), in mast cells. Using as a model, rat basophilic leukemia cells (RBL-2H3) stably transfected with cDNA encoding wild-type or mutated murine or human Fc gamma RIIB and chimeric molecules having the intracytoplasmic domain of the FcR gamma subunit or of TCR-CD3 zeta subunit, we found that the inhibitory properties of Fc gamma RII are neither restricted to B cells nor to BCR-dependent cell activation, but can be extended to other cells and, as a general rule, to TAM-dependent cell activation. PMID- 7797242 TI - Molecular dissection of Fc gamma receptor-mediated phagocytosis. AB - Using an experimental model in COS-1 cells, we have examined the structural requirements for phagocytosis of IgG-sensitized cells by Fc gamma receptors. We have established that isoforms of each of the 3 classes of the Fc gamma receptors, Fc gamma RI, Fc gamma RII and Fc gamma RIII, are able to transmit a phagocytic signal in the absence of the other receptor class. Fc gamma I and Rc gamma RIIIA require a gamma-subunit for this signaling event, but Fc gamma RIIA does not. Fc gamma RIIA and the gamma-subunit associated with Fc gamma RI and Fc gamma RIIIA contain 2 copies of a conserved tyrosine-containing cytoplasmic sequence, YXXL. This sequence is important for phagocytosis and is phosphorylated on tyrosine after receptor ligation. The Fc gamma receptors Fc gamma RIIB1 and Fc gamma RIIB2 which contain only 1 copy of the YXXL cytoplasmic sequence do not include the phagocytosis of IgG-coated cells. Thus, the Fc gamma receptor isoforms differ in their ability to transmit a phagocytic signal. Structure/function studies also indicate that the Fc gamma receptors which induce phagocytosis differ in their requirements for phagocytic signaling. PMID- 7797241 TI - Interaction of signaling molecules with human Fc gamma RIIb1 and the role of various Fc gamma RIIb isoforms in B-cell regulation. AB - The low-affinity type-IIb IgG Fc-binding receptors (Fc gamma RIIb) are expressed on B cells. When cross-linked with mIgM Fc gamma RIIb are known to down-regulate B-cell activation by interrupting signal transduction upstream from G-protein activated events. We have studied Fc gamma RII isoforms expressed on resting and activated B cells and the interaction of Fc gamma RIIb1 with molecules transducing the antigen receptor-mediated signals. Expression of Fc gamma RII isoforms was studied by reverse transcription and polymerase chain reaction. Resting B cells express both Fc gamma RIIb2 and Fc gamma RIIb1 isoforms. Activation with anti-IgM or IL-4 induces the splicing of Fc gamma RIIb1 mRNA, while the alternative splicing of Fc gamma RIIb2 mRNA is down-regulated, resulting in the surface expression of Fc gamma RIIb1. Functional differences were found between the two isoforms in inhibiting B-cell activation, suggesting that Fc gamma RIIb2 might influence the threshold of signals necessary for activation of resting B cells, while Fc gamma RIIb1 may regulate in later phases of antibody response. To explore the mechanism by which Fc gamma RII may uncouple antigen receptor-mediated signal transduction, we have investigated the association of signaling molecules with Fc gamma RII. Beside the protein tyrosine kinase (PTK) fyn, protein kinase C (PKC) was found to be co-isolated with Fc gamma RIIb1, suggesting a tight connection between these kinases and Fc gamma RII. We suggest that PKC might be responsible for the activation-induced phosphorylation of Fc gamma RII on serine residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797243 TI - Functional consequences of the interaction between T-cell antigen receptors and Fc gamma Rs on T cells. AB - Two series of experiments are presented indicating that Fc gamma II receptors can interfere with the antigen receptor-induced signaling on T cells. It has been previously described that a 13 amino acid motif on the cytoplasmic portion of Fc gamma II beta 1 can abrogate the antigen receptor-initiated signals mediated through consensus motifs present on the cytoplasmic portion of Ig alpha and Ig beta chains. Similar activating motifs are crucial to T-cell receptor (TCR) signaling. A splenic gamma/delta T-cell hybridoma that expressed the Fc gamma RII beta 1 receptor helped to establish that this receptor can also interfere with TCR-induced activation. The cytoplasmic portion of human Fc gamma RIIa has an activation motif similar to the activation motifs present on the TCR. Using a transgenic mouse in which the T cells express the human Fc gamma RIIa transgene, we demonstrated that despite the common activation motif, the TCR and human Fc gamma RIIa-induced signals are different. Additionally, the human Fc gamma RIIa expressing T cells exhibit an enhanced TCR response both in vitro and in vivo. PMID- 7797244 TI - Prognostic value of cytokine and soluble Fc gamma receptor assays in oncology. AB - The clinical course of a cancer is influenced by the interaction of tumour cells with the patient's immune system. It is thus conceivable that immunological parameters may be used as markers of prognostic or predictive value. We report here that increased serum levels of IL-6 is a signal of poor prognosis and predicts unresponsiveness to immunotherapy in patients with metastatic melanoma. In cervical cancer, IL-6 produced by infiltrating macrophages is a marker of invasive cancer. In patients with multiple myeloma, the plasmatic levels of soluble Fc gamma receptors are markers of the disease, sCD16 being drastically decreased and sCD32 being slightly increased. PMID- 7797245 TI - Developmental regulation of Fc epsilon RII/CD23 expression in B-lineage cells: evidence for transcriptional and post-transcriptional levels of control. AB - The present studies show that the expression of cell surface Fc epsilon RII/CD23, detected with the monoclonal anti-Fc epsilon RII/CD23 antibody B3B4 or by the binding of IgE, is not restricted to the stage of resting mature virgin B lymphocytes. Murine CD23 was detected as a cell surface protein on two sIgG+ B cell lines. Moreover, we detected full-length transcripts for Fc epsilon RII/CD23 in several members of a panel murine B lymphoid lineage cell lines representative of all stages of murine B lymphocyte development. Our findings suggest that regulation of CD23 translation may differ between B-cell lines at various stages of differentiation. The detection of mRNA transcripts for Fc epsilon RII/CD23 was not restricted to transformed cell lines. Fc epsilon RII/CD23 transcripts were amplified by RT-PCR from peritoneal and splenic B lymphocyte subpopulations that were sorted by flow cytometry into populations that did not express surface Fc epsilon RII/CD23. Our findings suggest that Fc epsilon RII/CD23 transcription and translation are not necessarily restricted to the narrow developmental window of murine B lymphocyte differentiation as previously thought. Our findings imply that Fc epsilon RII/CD23 may be expressed at the protein level at various stages of murine B lymphocyte differentiation. Investigations into the expression patterns and potential mechanisms of regulation of Fc epsilon RII/CD23 could provide insight into the basis for the wide range of immunological functions that have been proposed for Fc epsilon RII/CD23. PMID- 7797246 TI - Functional significance of CD23- on CD23-transfected Th2 clone. AB - CD23, a low-affinity IgE Fc receptor, is not displayed on most resting T cells but its expression has been shown to be transiently induced in vivo and in vitro on some CD4+ T cells [1-4] and in vivo on CD8+ T cells by IgE-secreting hybridoma tumors [5]. To investigate the functional role of CD23 on T cells, we inserted a CD23 construct into an expression vector driven by a CD2 promoter and transfected it into a murine Th2 clone D10.G4.1 (D10). We stimulated the transfected D10 cells (D10.3M.24) with anti-TCR antibody in the presence or absence of IgE, and measured IL-4, IL-5 and IL-6 production in the culture supernatants. Activation of D10.3M.24 cells by anti-TCR antibody induced greater levels of IL-4, IL-5 and IL-6 production, when the TCR and CD23 were co-crosslinked by TNP anti-TCR and IgE anti-TNP antibodies. IgG anti-TNP antibody did not enhance lymphokine production by D10.3M.24 cells. The enhanced lymphokine production by IgE was blocked by monoclonal anti-CD23 antibody. IgE anti-TNP antibody did not enhance lymphokine production by the wild-type D10 cells induced by TNP anti-TCR antibody. These studies show that when co-crosslinked with the TCR, CD23 can modulate the lymphokine production in activated Th2 cells. Since CD23 binds to IgE and also binds to CD21 [6], a complement receptor commonly expressed on B cells, T-cell CD23 could play an immunoregulatory role during cognate T-B cell interaction and during IgE antibody responses. PMID- 7797248 TI - Ligands and biological activities of soluble Fc gamma receptors. AB - Soluble forms of low-affinity Fc gamma receptors (sFc gamma R) circulate in biologic fluids. Their plasmatic levels vary in immunological disorders or related diseases. They are produced by enzymatic cleavage of the membrane receptors or by alternative splicing. They bind IgG with the same isotype specificity as their cell surface counterparts and thus modulate Fc-dependent immune functions. Recent data suggest that they also bind non-Ig ligands present on leukocytes. Functional implications of these findings are discussed. PMID- 7797247 TI - Identification of novel CD23 transcripts on human T and B lymphocytes and eosinophil cell line. AB - The main aim of the present studies was to investigate the structure of the human low-affinity IgE Fc receptor (CD23) present on T and B lymphoid cells and eosinophil cell line. A novel finding in these studies has been the detection and sequence analysis of CD23 transcripts in human T lymphocytes. These studies have established that some of the human T-cell populations analyzed express CD23 mRNA and that its structure is quite similar to that previously described for human B lymphocytes. A second major finding in these studies is that some human T- and B cell lines and eosinophil cell line contain multiple forms of CD23 transcripts. These appear to be generated via alternative splicing, resulting in transcripts that may encode a truncated, possibly secretory form of CD23. These findings in human T and B lymphocytes and eosinophils provide new information about the structure of lymphocyte CD23 and suggest that alternative processing of transcripts generates CD23 mRNA that encodes CD23 isoforms. These studies are the first experimental evidence showing that CD23 isoforms may occur in the human and are the first direct evidence for production of CD23 by human T lymphocytes. In addition, these studies provide the first experimental evidence that T and B lymphocytes express CD23 transcripts lacking exon 3-encoded sequences, raising the possibility that a secretory form of CD23 may be synthesized by human T and B lymphocytes, and eosinophils. PMID- 7797249 TI - Expression of the complement C5a anaphylatoxin receptor (C5aR) on non-myeloid cells. AB - The expression of the complement C5a anaphylatoxin receptor (C5aR) has traditionally been thought to be limited to myeloid blood cells, including neutrophils, monocytes, macrophages, and eosinophils. Immunohistochemistry and ligand-binding studies reported here demonstrate, however, that C5aR is expressed by parenchymal cells of several solid organs, including human liver hepatocytes, lung bronchial and alveolar epithelial cells, and lung vascular smooth muscle and endothelial cells. In addition to C5aR expression in liver and lung, C5aR specific message is found in other tissues, including the spleen, heart, kidney, and intestine. Collectively, these data indicate that the C5aR is expressed in several different types of cells in liver and lung and in yet undetermined cell types in spleen, heart, intestine, and kidney. Moreover, these data suggest that the C5aR mediates previously unrecognized functions by binding to tissue cells that express the C5aR. PMID- 7797250 TI - Induction of ADF/TRX by oxidative stress in keratinocytes and lymphoid cells. AB - Adult T-cell leukemia-derived factor (ADF)/human thioredoxin (TRX) has thiol dependent reducing activities and is known to have regulatory roles on the DNA protein interaction and cell activation. Inducive effect of ultraviolet (UV) has been indicated because of the enhanced expression of ADF/TRX in epidermal cells of sun-exposed skin, as determined by immunohistochemical staining with antibody against recombinant ADF (rADF). We studied the effect of UVB irradiation and other oxidative stress on the expression of ADF/TRX in epithelial cells as well as lymphoid cells, as HTLV-1 and Epstein-Barr virus-transformed lymphoid cells constitutively produce ADF/TRX. Using immunohistochemical staining anti-ADF antibody, the enhancement of ADF/TRX expression on primary culture of human keratinocytes was demonstrated, 12 h after 20 mJ/cm2 UVB irradiation. Western blot analysis of the ADF/TRX protein in the cell lysates also showed the significant induction. In in situ hybridization, induction of ADF/TRX mRNA was detected after 4 h of UV exposure. ADF/TRX was also induced in a HTLV-1 (+) T cell line, MT-1, by UVB or H2O2 dose dependently. The augmentation of ADF/TRX was observed 6 h after treatment of H2O2. PMID- 7797251 TI - Selective steady-state and time-resolved fluorescence spectroscopy of an HLA-A2 peptide complex. AB - The human class I major histocompatibility complex (MHC) encoded molecule HLA-A2 loaded with the high-affinity peptide GILGRVFTL (p790), was studied by means of steady-state and picosecond fluorescence intensity and fluorescence anisotropy methods. The large number of tryptophan residues (W) (10 W/heavy chain, 2 W/beta 2m) as well as their fluorescence sensitivity to the microenvironment, determine the emission of the studied complex. The HLA-A2/peptide complex exhibits a considerable static inhomogeneous broadening (IB) of the W electronic spectra, which results in a dependence of the steady-state fluorescence spectrum on the excitation wavelength. The high concentration of W's chromophores and the spectral IB cause a directed non-radiative migration of electronic excitation energy by Foerster's mechanism from 'blue' W residues to 'red' ones. This phenomenon manifests itself in a nanosecond fluorescence spectral shift and an accelerated fluorescence depolarization at the red edge of the emission spectrum. Selective excitation at the red edge of the W absorption band (310 nm) provided a space selective reduction in the number of excited chromophores and enabled resolution of the emission of the 'red' subset of the protein's tryptophans. This avoided the non-radiative homo-energy transfer and enabled to study the fluorescence anisotropy decay kinetics of these residues without a distortion by the energy transfer (ET) process. Under these experimental conditions the fluorescence anisotropy decays practically from the limiting anisotropy value (0.3) for W in a bi-exponential process. The longer decay constant has a value larger than that expected for a global rotation of the HLA-A2/peptide complex suggesting that the protein molecules exist in an oligomeric form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797252 TI - Distinct association of transferrin receptor with HLA class I molecules on HUT 102B and JY cells. AB - The topological relationship of transferrin receptor (TfR) has been studied relative to the heavy and light chains of the HLA class I molecules, class II molecules, interleukin-2 receptor alpha-chain and ICAM-1 molecule in the plasma membrane of HUT-102B2 T and JY B lymphoblastoid cell lines using the flow cytometric fluorescence energy transfer technique (FCET). The effect of different growing conditions (logarithmic and plateau phases) on the relative surface density of the receptors and the lateral organization of the TfR was also studied. The TfR showed a high degree of self-association on the surface of both cell lines regardless of the growing phase. TfR was in close vicinity to HLA class I heavy and light chains on HUT-102B cells in both plateau and logarithmic phases, while it was not associated with HLA class I on the surface of JY cells. HLA class II molecules form a cluster with TfR on HUT-102B cells, while only a modest association was found on JY cells, and only in the logarithmic phase. The possible explanation of this distinct association and a two dimensional model of the antigen and receptor distributions are presented in this paper. PMID- 7797253 TI - Microenvironmental factors regulate Ly-6 A/E expression on PyV-transformed BALB/c 3T3 cells. AB - In previous studies non-lymphoid murine tumor cells were sorted by flow cytometry, into 2 subpopulations. The one expressed high levels of the T-cell activation protein Ly-6 A/E and the other low levels of this protein. High Ly-6 A/E expression was associated with very high tumorigenicity and metastatic phenotypes. Cells expressing low levels of this protein expressed a significantly reduced malignancy phenotype as compared to unsorted tumor populations. In view of its direct (or indirect) involvement in tumor progression we studied, in the present work, the regulation by microenvironmental factors of Ly-6 A/E expression on A3C polyoma-virus transformed cells. Ligation of membrane Ly-6 A/E by the corresponding monoclonal antibodies resulted in up-regulated expression of this protein. Similar results were obtained by exposing A3C cells to interferon-alpha. In contrast, exposing tumor cells to tumor necrosis factor-alpha or to the extracellular matrix protein laminin resulted in a down-regulation of Ly-6 A/E expression on these cells. These results provide an additional insight into the role microenvironmental factors might play in tumor progression. PMID- 7797254 TI - Interleukin-2 induces an early step in the activation of interferon-gamma gene expression. AB - Establishment of protective immunity depends critically on IFN-gamma. We show that in human peripheral blood mononuclear cells, low doses of IL-2 greatly potentiate the response of the IFN-gamma gene to mitogen, by over 100-fold. By itself, IL-2 is unable to induce IFN-gamma mRNA to a significant extent. Yet, exposure to IL-2 leads to cellular commitment within a few hours, expressed by greatly enhanced accumulation of IFN-gamma mRNA upon subsequent exposure to phytohemagglutinin. Changes induced by IL-2 do not relieve the requirement for de novo protein synthesis during the early phases of induction of IFN-gamma gene expression. IL-2 may induce a component essential for induction of IFN-gamma mRNA that is utilized during subsequent exposure to a mitogenic signal. Our results demonstrate synergy between IL-2 and mitogen in IFN-gamma gene induction. PMID- 7797257 TI - Proceedings of the 8th Symposium on Signals and Signal Processing in the Immune System. Kecskemet, Hungary, 18-22 September 1994. PMID- 7797256 TI - Cytokine receptor architecture, structure and genetic assembly. AB - In this review major structural and molecular characteristics of interleukin-6 type cytokine receptors consisting of ligand-specific (e.g., IL-6 receptor) and public (gp130) elements are outlined. The peculiar shedding feature of the ligand binding receptor subunit provides a possibility to form a receptor-ligand complex in the soluble phase, followed by an autocrine or paracrine re-attaching to the membrane bound gp130. This situation provides a dynamic 4-chain model for IL-6 type receptors, depending on a critical balance between membrane bound and soluble cytokine receptors. The generation and transduction of intracellular signal for IL-6-type cytokine receptors based primarily on generation of phospho tyrosine proteins. In this set of events kinases of the JAK family are basically involved. Although not all primary substrates are uncovered, gp130 and stat proteins are phosphorylated. The variability of the JAK/Stat system and its still not clear relation to the specificity of cytokine actions are discussed. PMID- 7797255 TI - Cholinergic signals to and from the immune system. AB - This article reviews recent data from our laboratory towards the impact of the autonomous nervous system on mutual interactions between the immune system and the central nervous system. Using a pharmacological approach in rats it is shown that shifts in the adrenergic/cholinergic balance in vivo affect in vitro functions of the non-specific and specific immune system, whereby adrenergic and cholinergic stimulation in general have opposite effects. A high degree of integration appears to exist between cells of the immune system with the cholinergic system. Lymphocytes were found to react to acetylcholine, but are also able to produce and to degradate this neurotransmitter. In addition, changes in the cholinergic tonus were found to affect immune signaling to the brain and to protect thymocytes from apoptosis, possibly via a direct effect on thymic epithelial cells. PMID- 7797258 TI - Differential binding activity of ARH1/TAM motifs. AB - T- and B-cell antigen receptors, and certain receptors for IgG and IgE constant regions, transduce signals via a conserved amino acid sequence motif, termed ARH1 or TAM. Receptor ligation leads to phosphorylation of 2 tyrosines found within the motif and this phosphorylation appears critical for signal transduction. Although this 26-residue motif exhibits some functional redundancy, its variability in sequence and occurrence in multiple forms in individual receptor complexes, e.g., as many as 8 copies in TCR, suggests that individual ARH1 motifs may exhibit partially unique function. To begin to address this possibility, we compared the binding activity of doubly phosphorylated and non-phosphorylated Ig alpha, Ig beta, TcR zeta c and CD3 epsilon ARH1 motifs. Results demonstrate a clear difference in binding activity determined by both motif phosphorylation and primary structure. Among non-phosphorylated motifs, Ig alpha exhibits the most readily detectable binding activity; binding src-family kinases [1], CD22, MAPK, PI3-k, and Shc, but not CD19. Among doubly phosphorylated motifs, Ig alpha, Ig beta, TCR zeta c and CD3 epsilon all exhibit binding activity but have distinct effector preferences. For example, while Ig alpha prefers src-family kinases over the Syk kinase and binds Shc avidly, CD3 epsilon prefers Syk over src-kinases and does not bind Shc. TCR zeta c seems to bind Syk, src-kinases and Shc. These data are consistent with the possibility that ARH1 motifs may be coupled to distinct signal propagation mechanisms. PMID- 7797259 TI - Function of B-cell antigen receptor of different classes. AB - Most mature B lymphocytes co-express two classes of antigen receptor, IgM and IgD. The differences in the signal transduction from the 2 receptors are still a matter of controversy. We have analysed B-cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen or class-specific antibodies results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetics and intensity of phosphorylation, however, were quite different between the 2 receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum already after 1 min and diminished after 60 min whereas in the membrane IgD expressing cells, the substrate phosphorylation increases further over time, reached its maximum at 60 min and persisted longer than 240 min after exposure to antigen. Recently prolonged signaling has been found to be responsible for signaling differences between tyrosine kinase receptors using otherwise similar signaling routes. Thus, the duration of a signal may be an important biological feature of signal transducing cascades. PMID- 7797260 TI - A signal strength hypothesis of thymic selection: preliminary considerations. AB - During their differentiation, thymocytes are subjected to two rounds of selection. First, CD4-8- double-negative (DN) thymocytes with a functional TCR beta chain express a alpha-beta+ CD3 complex on their surface and, as a consequence, are selected to mature to the CD4+8+ double-positive (DP) stage. This round ends after the initial proliferation of young DP thymocytes and is termed beta-chain selection. Second, DP thymocytes are selected on the basis of their alpha+beta+ CD3 complex. This is termed repertoire selection and the cells are given three choices: death by neglect selection, death by positive selection, or deletion by negative selection. Using anti-CD3 epsilon mAb as invariant ligand, signals for beta-chain selection of DN cells including proliferation of DP cells do not require a Ca2+ response, are independent of CD3 zeta, and are only slightly impaired in the absence of p56lck (lck). Signals that induce positive selection of DP thymocytes require a partial Ca2+ response and CD3 zeta but are independent of lck. Deletion of DP thymocytes requires a full-blown Ca2+ response and both, CD3 zeta and lck. Thymic selection thus appears to be governed by a gradient of signal intensities. PMID- 7797261 TI - Ion-channel activities regulate transmembrane signaling in thymocyte apoptosis and T-cell activation. AB - Several examples have shown that plasma membrane ion channels (e.g., Ca2+ and K+ channels) make an important contribution to lymphocyte activation or thymocyte apoptosis. Here we report on the importance of these ion channels in the sensitivity or resistance of lymphoid cells to extracellular ATP-induced apoptosis. Thymocytes of Balb/c mice responded to extracellular ATP (ATPex) sensitively, with an immediate increase in the intracellular calcium level and later with an increased membrane permeability to low MW markers. Mature (medullary) thymocytes showed a higher sensitivity than did cortical thymocytes. Three human lymphoma cell lines, including SUPT13, a cell line reported to be sensitive to TcR/CD3 activation-induced apoptosis, showed a high resistance to ATPex action. These observations suggest that maturation/differentiation state dependent activity or disappearance of early ATP-receptor operated signaling systems (including ion channels) are critical for the cells in developing towards apoptosis. Using the patch-clamp technique we demonstrated that bretylium tosylate (a particular K(+)-channel blocker) known as inhibitor of T-lymphocyte proliferation also influences the single-channel properties of voltage-gated K+ channels through depressing whole-cell K+ currents. This finding is yet another example underlying the importance of K+ channel activity in T-lymphocyte proliferation. PMID- 7797263 TI - Sequence analysis of the human alpha beta T-cell receptor CDR3 region. AB - Although the three-dimensional structure of the T-cell receptor (TCR) has not yet been determined, several groups have proposed that the outline structure of the TCR will closely resemble that of immunoglobulin (Ig). Hypervariable regions can be identified within the TCR variable (V) domains, and by analogy to similar regions in the Ig molecule which together form the antigen combining site these have been termed the complementarity determining regions (CDR) 1, 2, and 3. By far the greatest extent of variability occurs at CDR3 and this has led to the proposal that CDR3 is involved in interaction with the peptide bound within the cleft of a major histocompatibility complex (MHC) molecule. We have cloned and sequenced the CDR3 region of several hundred human TCRA and TCRB transcripts from different T-cell populations and studied the amino acid usage in this region. Results show that the average length of the CDR3 region is 10 amino acids with less variation in length than is seen for the Ig heavy chain. There is no difference in CDR3 length between fetal and adult T cells or between CD4 and CD8 populations. The pattern of amino acid usage in the CDR3 region is dissimilar between TCRA and TCRB transcripts. In particular there is a predominance of charged and polar residues in the region of the TCRA transcript thought to interact with peptide. These data provide information on the general pattern of CDR3 length and composition for both TCRA and TCRB. PMID- 7797262 TI - Cloning and sequencing of expressed DRB genes of the red deer (Cervus elaphus) Mhc. AB - The expressed major histocompatibility complex (Mhc) class II DRB genes of 50 unrelated deer were examined by reverse transcription polymerase chain reaction, cloning, and sequencing of DRB exon 2. Deer, like other mammals, have at least one highly polymorphic Mhc class II DRB gene. Thirty-four different sequences were identified. Most of the variation in amino acid composition occurred at positions that have been shown to form the peptide binding site (PBS). Eighteen deer-specific substitutions were found, 11 of these occurred in the PBS. Significantly higher rates of replacement substitutions than silent substitutions were found in the deer sequences, indicating strong positive selection pressure for diversity in DRB sequences. Between one and four DRB sequences were found per deer. Inheritance of these sequences in pedigrees showed Mendelian segregation with up to two expressed DRB genes per haplotype. Sheep are the only other ruminant in which the presence of more than one expressed DRB gene has been demonstrated. Phylogenetic trees were constructed in an attempt to assign the deer DRB sequences to specific loci, but no clear segregation of the DRB sequences for different loci was found. It would seem likely that sequence exchange between the loci has occurred. As has been shown in other species, the alpha-helix and beta-sheet regions of exon 2 appeared to have different evolutionary histories. PMID- 7797265 TI - Characterization and mapping of the gene encoding mouse proteasome subunit DELTA (Lmp19). AB - The proteasome subunit DELTA is unusually closely related to the major histocompatibility complex (MHC)-linked proteasome subunit, LMP2. The sequence of a mouse cDNA for DELTA confirms that this 22,100 M(r) proteasome subunit is highly conserved across species. Sequence analysis of the mouse gene encoding DELTA, designated Lmp19, indicates that it consists of six exons and five introns, similar to the Lmp2 gene. The 5' upstream region lacks a TATA regulatory sequence, which is also absent from proteasome genes isolated from Drosophila. BXD recombinant inbred (RI) mice were used to map the potential chromosomal location of Lmp19, and revealed that the DELTA subunit has related sequences present on two different mouse chromosomes, chromosomes 1 and 11. Typing of 89 progeny from a C57BL/6J X Mus spretus DNA backcross panel (BSS) confirmed the chromosome 1 assignment. Southern hybridization with a polymerase chain reaction generated Lmp19 intron 2-specific probe indicates that the Lmp19 genomic clone corresponds to the sequence on chromosome 11, and further suggests that the chromosome 1 copy represents a processed pseudogene (Lmp19-ps1). PMID- 7797266 TI - Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis. AB - Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule. PMID- 7797264 TI - HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles. AB - Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles. PMID- 7797267 TI - Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution. AB - The complement component C4 genes of Old World primates exhibit a long/short dichotomous size variation, except that chimpanzee and gorilla only contain short C4 genes. In human it has been shown that the long C4 gene is attributed to the integration of an endogenous retrovirus, HERV-K(C4), into intron 9. This 6.36 kilobase retroviral element is absent in short C4 genes. Here it is shown that the homologous endogenous retrovirus, ERV-K(C4), is present precisely at the same position in the long C4 gene of orangutan and African green monkey. Determination of the short C4 gene intron 9 sequences from human, three apes, two Old World monkeys, and a New World monkey allowed the establishment of consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla clade. The 5' long terminal repeats (LTR) and 3' LTR of ERV-K(C4) in long C4 genes of human, orangutan, and African green monkey have similar sequence divergence values of 9.1%-10.5%. These values are more than five-fold higher than the sequence divergence of the homologous intron 9 sequences between the long and short C4 genes in higher primates. The latter is probably a result of homogenization or concerted evolution. We suggest that the 5' LTR and 3' LTR of an endogenous retrovirus can serve as a reliable reference point or a molecular clock for studies of gene duplication and gene evolution. This is because the 5'/3' LTR sequences were identical at the time of retroviral integration and evolved independently of each other afterwards. Our data provides strong evidence for the short C4 gene being the ancestral form in primates, trans-species evolution, and the "slow-down" phenomenon of the sequence divergence in great apes. PMID- 7797269 TI - Physical and genetic linkage of the genes encoding Ly-9 and CD48 on mouse and human chromosomes 1. AB - By virtue of sequence similarity, the genes encoding CD2, CD48, CD58, and Ly-9 have been assigned to a distinct subset within the immunoglobulin superfamily. Previous gene mapping studies in human and mouse have suggested that CD2, CD48, and CD58 arose by gene duplication. Here we show the gene encoding Ly-9 to be located adjacent to CD48 and the Na,K-ATPase alpha 2 subunit gene on human and mouse chromosome 1. The proximity in human and mouse genomes of the genes encoding CD2, CD58, and the Na,K-ATPase alpha 1 subunit, and of the Ly-9, CD48, and the Na,K-ATPase alpha 2 subunit genes may be explained by the occurrence of two, successive duplication events during vertebrate evolution, and suggest that Ly-9 may also participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction. PMID- 7797268 TI - Diversity of TCRAV and TCRBV sequences used by human T-cell clones specific for a minimal epitope of Bet v 1, the major birch pollen allergen. AB - T-cell clones (TCC) were raised from the peripheral blood of patients suffering from tree pollen allergy. All TCC were restricted by HLA-DR molecules. In order to investigate possible intervention targets in Type I allergic diseases, we examined T-cell receptor (TCR) alpha and beta chain nucleotide sequences of five allergen-reactive human CD4+ TCC specific for a C-terminal epitope (BV 144) of Bet v 1, the major birch pollen allergen. Proliferation assays using synthetic peptides revealed the 10-mer LRAVESYLLA as minimal epitope for three TCC; two TCC also displayed reactivity with the nonapeptide LRAVESYLL. Two TCC expressed TCRBV2S3, all other BV144-specific TCC used diverse TCRAV and TCRBV gene segments. Moreover, the junctional regions encoding the third complementary determining regions (CDR3) of the TCR showed a striking heterogeneity in length and amino acid composition. Nevertheless, all TCC showed an arginine residue in the N-terminal region of their TCRBV CDR3 loops. Therefore, therapeutical strategies aimed at the clonal deletion of allergen-specific T-cell clones, providing help for IgE synthesis, will not be feasible. Our results cast a doubt on the theory that the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest additional interaction with MHC class II. PMID- 7797270 TI - Rat RT1 orthologs of mouse H2-M class Ib genes. PMID- 7797271 TI - Rfp-Y-like sequences assort independently of pheasant Mhc genes. PMID- 7797272 TI - The MHC class I-like Zn-alpha 2-glycoprotein gene maps to mouse chromosome 5. PMID- 7797273 TI - Cattle cDNA clones encoding MHC class II DQB1 and DQB2 genes. PMID- 7797274 TI - Gastroesophageal reflux and asthma. PMID- 7797275 TI - Airway response to acid instillation in esophagus in bronchial asthma. AB - OBJECTIVE: An increased incidence of gastroesophageal reflux has been reported in patients with bronchial asthma. We studied the pulmonary effects of acid instillation in the esophagus. METHODS: Fifteen patients with bronchial asthma and 15 healthy adults in the age group 15-50 years were studied. The control subjects were first screened for bronchial hyperreactivity by a methacholine challenge test. Patients and controls were both subjected to modified Bernstein test. Spirometry was done at baseline and after each instillation of either acid or saline. Respiratory and reflux symptoms were noted after each infusion and antacid administration. RESULTS: Five patients and one control subject had history of reflux symptoms (p < 0.05) and six patients had nocturnal asthma. There was a significant fall in FEV1/FVC after acid infusion patients; this improved significantly after antacid administration. All six patients with nocturnal asthma had respiratory signs or symptoms and had more than 20% fall in FEV1 on acid instillation in the esophagus, while none in the control group developed the same. CONCLUSIONS: Gastroesophageal reflux occurs more frequently in patients with bronchial asthma and acid instillation in the esophagus triggers bronchoconstriction. PMID- 7797276 TI - Effect of sucralfate on gastric bicarbonate secretion in patients with duodenal ulcer. AB - BACKGROUND: Sucralfate is known to protect gastroduodenal mucosa and thereby facilitate healing of peptic ulcer. The mechanism of action of this drug is still not fully known. METHODS: We studied the effect of sucralfate treatment on gastric bicarbonate secretion in 16 patients with duodenal ulcer. RESULTS: Sucralfate administration (3 g daily for 4 weeks) stimulated bicarbonate secretion from 3.1 +/- 1.2 mmol/h to 4.6 +/- 2.0 mmol/h (p < 0.05). Gastric juice volume as well as non-parietal volume secretion also increased significantly after sucralfate therapy (p < 0.05). CONCLUSION: Sucralfate causes stimulation of non-parietal volume-dependent gastric bicarbonate secretion. PMID- 7797278 TI - Primary repair or colostomy in the management of civilian colonic trauma. AB - BACKGROUND: Management of civilian colonic trauma remains controversial. AIM: To determine prognostic factors in patients with civilian colonic trauma undergoing different modes of therapy. METHODS: Sixty-five patients with colonic injuries were retrospectively analyzed. RESULTS: Right and left colon injuries were present in 30 and 35 cases respectively. Colon-related complications occurred in 27.7%. One death (1.5%) was directly due to colonic injuries. Left sided colon injuries led to a higher incidence of complications and longer duration of hospital stay; a higher number of complications occurred in relation to colostomy than primary closure. CONCLUSIONS: Primary repair can be done in more cases than is routinely done. The presence of multiple abdominal injuries or shock does not exclude primary repair. The site of injury may affect the outcome, but does not exclude primary repair. Gross fecal contamination, extensive colonic damage and type of feces in affected colon should be considered as indications favoring colostomy. PMID- 7797277 TI - Serum zinc levels in hepatic encephalopathy. AB - BACKGROUND: Zinc is essential for various metabolic processes of the body. Since serum zinc levels are lowered in liver diseases, it has been postulated to be a precipitating factor for hepatic encephalopathy. METHODS: We prospectively studied serum zinc levels in consecutive patients with fulminant hepatic failure, subacute hepatic failure and chronic liver disease with encephalopathy. Serum zinc levels were correlated with various clinical and biochemical parameters and final outcome of patients. Serum zinc levels were estimated by atomic absorption spectrometry at admission and also 24 hours after recovery in survivors. RESULTS: Of the 55 patients (age 17-65 years, 35 men) studied, 30 had acute, 5 subacute and 20 chronic liver disease. Patients with hepatic encephalopathy had significantly lower serum zinc levels as compared to 20 age and sex matched controls. High serum bilirubin levels and prothrombin time showed inverse relationship with serum zinc levels. There was no relationship of serum zinc levels with age, sex, grade and duration of encephalopathy, liver size, ascites or splenomegaly. CONCLUSIONS: Hepatic encephalopathy is associated with low serum zinc levels. Recovery occurred in 17 patients despite persisting low serum zinc levels. Serum bilirubin > 23 mg/dL and prothrombin time prolongation > 12 seconds above control have inverse correlation with serum zinc level. PMID- 7797280 TI - Mechanisms of cholesterol gallstone formation. PMID- 7797279 TI - Malondialdehyde levels in patients with duodenal ulcer. AB - Malondialdehyde (MDA) is a stable product of lipid peroxidation of membrane lipids. In view of its role in membrane lipid damage in various inflammatory disorders, MDA levels were estimated in 83 duodenal ulcer patients and 48 controls. MDA levels were found to be significantly higher in duodenal ulcer patients as compared to controls (mean +/- SD 280.2 +/- 109.0 versus 216.5 +/- 81.4 nm/dL, p < 0.001). These increased levels of MDA may represent either the result of peroxidative damage in the disease process or a pathogenetic factor enhancing the risk for duodenal ulcer. PMID- 7797282 TI - Conversion of loop colostomy to end colostomy: is dismantling necessary? AB - Twelve patients who had previously undergone preliminary pelvic loop colostomy were treated by conversion of loop colostomy to end colostomy by alternative technique ie without dismantling of loop and conversion to end stoma. The results of this technique were compared with those of conventional procedure which was performed in ten patients. The new technique results in a 'mature' end colostomy in situ with little pain at the stoma site, no risk of retraction and lower risk of peristomal infection. We therefore recommend this procedure for all patients needing such conversion. PMID- 7797281 TI - Treating irritable bowel syndrome. PMID- 7797283 TI - Esophageal candidiasis following omeprazole therapy: a report of two cases. AB - Esophageal candidiasis was diagnosed at endoscopy in two patients receiving omeprazole therapy. There was no clinical evidence of immunosuppression or any obstructive lesion in the esophagus. There was prompt response of oral ketoconazole. These cases suggest that marked acid reduction may predispose to esophageal candidial infection. PMID- 7797285 TI - Sigmoido-rectal intussusception. AB - Sigmoido-rectal intussusception is the least common type of intussusception seen in infants and children and is therefore usually misdiagnosed as rectal prolapse. Delay in diagnosis and treatment is due to lack of its awareness amongst surgeons, incomplete assessment of the prolapsed bowel at the anal orifice, and absence of classical traid of intussusception i.e. palpable abdominal mass, colicky abdominal pain, and bleeding per rectum. PMID- 7797284 TI - Colovesical fistula complicating colonic diverticulosis. AB - Two cases of colovesical fistulae secondary to colonic diverticulosis are reported. Urinary symptoms were the prominent presenting features. Barium enema was helpful in documenting the fistulae, which cystoscopically was not localised. Definitive treatment included resection of the fistula and the diseased segment of the intestine. Both patients are well on follow-up. Diverticulosis coli should be considered in the differential diagnosis of colovesical fistulae even in tropical countries. PMID- 7797286 TI - Gastric wall necrosis in an HIV-positive patient. AB - Perforation of the gastrointestinal tract is rare in HIV infection and occurs most often in the colon and small intestine. Gastric perforation in HIV-positive patients has not been reported so far. We report an HIV-positive patient who developed gastric perforation. PMID- 7797287 TI - Gallstone obstruction of the duodenum (Bouveret's syndrome). AB - Bouveret's syndrome is a rare complication of gallstones, leading to duodenal obstruction. We report a 25-year-old woman with this condition, probably the youngest patient reported. PMID- 7797288 TI - Obstructive jaundice due to Fasciola hepatica. AB - A middle aged woman presented with obstructive jaundice of 6 months duration. Radiological investigations revealed multiple pyogenic liver abscesses with the possibility of choledocholithiasis. Exploration of common bile duct revealed that Fasciola hepatica was responsible for the illness. The case is reported because of its rarity. PMID- 7797289 TI - Unusual foreign body in intestine: marble chips. PMID- 7797290 TI - Auto-amputation of vermiform appendix. PMID- 7797291 TI - Basic issues in estimating and comparing the survival of cancer patients. PMID- 7797292 TI - The EUROCARE database. PMID- 7797293 TI - Methods of data analysis. PMID- 7797294 TI - General mortality and its effect on survival estimates. PMID- 7797295 TI - Survival of cancer patients in Europe. Summary and discussion of results. PMID- 7797297 TI - Health care system, cancer registration and follow-up of cancer patients in Estonia. PMID- 7797296 TI - Health care system, cancer registration and follow-up of cancer patients in Denmark. PMID- 7797298 TI - Health care system, cancer registration and follow-up of cancer patients in Finland. PMID- 7797299 TI - Health care system, cancer registration and follow-up of cancer patients in France. PMID- 7797300 TI - Health system, cancer registration and follow-up of cancer patients in Germany (West). PMID- 7797301 TI - Health care system, cancer registration and follow-up of cancer patients in Italy. PMID- 7797302 TI - Health care system, cancer registration and follow-up of cancer patients in The Netherlands. PMID- 7797303 TI - Health care system, cancer registration and follow-up of cancer patients in Poland. PMID- 7797304 TI - Health care system, cancer registration and follow-up of cancer patients in Spain. PMID- 7797305 TI - Health-care system, cancer registration and follow-up of cancer patients in Switzerland. PMID- 7797306 TI - Health care system, cancer registration and follow-up of cancer patients in the United Kingdom. PMID- 7797308 TI - Survival of cancer patients in Europe. Results. PMID- 7797307 TI - Survival of cancer patients in Europe. Guide to tables. PMID- 7797309 TI - Plague. PMID- 7797310 TI - Maternal behaviour and feeding practices as determinants of childhood diarrhoea: some observations among rural Begalee mothers. PMID- 7797311 TI - Health economic concepts, issues & challenges. PMID- 7797312 TI - Study of the impact of epidemiological factors on intelligence of rural children of 3 to 6 years age group belonging to low socio-economic status. AB - There are many factors which affect intelligence as well as physical growth of children, although genetic factor plays a prime role but social, environmental and psychological factors influence significantly the physical growth and intelligence of the child and the same can be improved through intervention. Community based studies are therefore useful to understand effect of these factors for future planning. The present study was therefore undertaken in Burdwan district of West Bengal with the objectives of studying level of intelligence of children of 3 to 6 years age group and impact of the factors related to the level of intelligence of these children. 72 children of 3 to 6 years age group were studied, of which 2/3 were either normal or having Grade-I undernutrition and the rest were either Grade-II or Grade-III. A significant positive association was found between DST IQ score (Bharat Raj) and the nutritional grade. Non-formal education also was found to have significant bearing on the IQ level. No significant relationship was however found between DST IQ score and the religion indicating culture independence of the scoring system. PMID- 7797313 TI - Resurgence of malaria in eastern and north-eastern region of India: a critical appraisal. AB - The implication of recent resurgence of malaria in eastern (E) and northeastern(NE) states of India critically urges an in-depth viewpoint into the rationale of implementation of National Malaria Eradication Programme (NMEP). The article highlights the regional scenario, considering the programme performance in this context. PMID- 7797314 TI - Measuring the interactions of the determinants of health. PMID- 7797315 TI - Factors influencing mode of claims settlement in workers' compensation cases. AB - This paper examines the variables that influence the means by which 10,192 injured workers settled their compensation claims during 1990. The data on which this study is based come from a state in Australia where there are three means by which workers' compensation claims can be settled by lump sum payment: settlement following a specific injury payment, early settlement payment and settlement following a common law payment. This paper is specifically concerned with identifying the variables that determine whether the claim will be settled by a lump sum payment and whether different modes of claims settlement by lump sum are unique and predictable from a range of variables that include injury characteristics and demographics. The results of logistic regression modelling revealed that those who received a lump sum settlement could be reliably distinguished from those who did not receive such a payment. Each mode of settlement varied in the extent to which it could be predicted. Contrary to expectations, the most difficult form of settlement mode to predict was that of specific injury payments (4% accurate) with the most predictive being early settlement payments (81% accurate). Common law payments were also highly predictable (48% accurate). The form of lump sum payment received by injured workers was found to depend on a range of injury characteristics, indices of severity and for common law payments, gender and potential income loss. It is argued that although injury characteristics play a part in the process of claims settlement, personal circumstances and insurance company policies are influential in dictating the form by which workers compensation cases are finalized. PMID- 7797316 TI - Factors influencing the disabled's employment in the competitive labour market. AB - Factors influencing the disabled's job search outcome were studied by means of material representing disabled job seekers (n = 1353) in three Finnish Employment Service Agencies during 1988-89. The job search outcome was defined successful if a job seeker was employed in the competitive labour market according to the ESA files during a follow-up period of 12-18 months and no unemployment was registered. The factors studied were age, gender, domicile, basic education, vocational training and disability. First, the relationship of the above factors to job search outcome was described bivariately, then it was studied by means of logistic regression models for men and women separately. The results were somewhat gender specific. For men, inadequate basic education had a negative influence on job search outcome, while for women, the outcome was influenced by domicile. Older disabled job seekers, both male and female, were disadvantaged. The problems created by age and disability are a challenge to rehabilitation. The results also point out adult training as a means for improving the disabled's labour market status. Finally, all of the disabled's problems are not on the individual level: it is not only who you are but also where you live that matters. PMID- 7797317 TI - Analysing work performance problems--methods and their effectiveness. AB - This paper explores methods of analysing work performance problems. It begins by looking at what can be understood by the term 'work performance problems' and offers a definition. The author clarifies the differences between work performance problems and negative work behaviours, to eliminate any confusion that may exist. There follows a review of some possible causes of work performance problems, as identified by a number of writers. Eight methods for analysing work performance problems are described. The difficulties of evaluating the effectiveness of methods for analysing work performance problems are highlighted and the range of variables that need to be accounted for are discussed. PMID- 7797318 TI - Perceptions of positive attitudes toward people with spinal cord injury. AB - This study identified differences in perceptions of positive attitudes toward persons with spinal cord injury (SCI). The four groups surveyed included 35 people with SCI, 27 rehabilitation workers from an acute spinal rehabilitation unit, 16 rehabilitation workers from an out-patient hospital rehabilitation unit and 37 people from the general population. Participants completed the Modified Issues in Disability Scale-Transitional Version. The people with SCI were considered the judges of what a positive attitude consisted of and scored higher on the measure than all other groups. The results showed that the acute spinal rehabilitation workers and the general population group differed significantly from the people with SCI in their perceptions of positive attitudes, whereas the out-patient hospital rehabilitation workers did not. Age and ethnic identity were significantly related to perceptions of attitudes, with younger adults and European New Zealanders being more aware of positive attitudes than older adults. Maori New Zealanders and Pacific Islanders. Professionally trained rehabilitation workers had a greater awareness than in-service trained workers of what constituted a positive attitude towards people with SCI. However, gender and amount of contact with people with disabilities were not related to perceptions of positive attitudes. PMID- 7797319 TI - Inter-rater reliability of a paediatric outcome measure in Nepal. AB - The Hospital and Rehabilitation Centre for Disabled Children (HRDC) in Nepal identified the need to evaluate their in-hospital and community programmes. An instrument was developed to provide information regarding the functional level of the children treated by the HRDC as well as to provide information regarding care givers' attitudes towards disability. Inter-rater reliability of the measure was tested in three regions of Nepal with 49 children. Six HRDC field workers travelled in pairs to the childrens' homes and alternated in roles as test administrator and observer. Correlations between the scores documented by the administrator and observer were used to estimate inter-rater reliability. Inter rater reliability coefficients, calculated using a weighted kappa statistic, varied from 0.60 to 1.0. We conclude that the instrument demonstrated an acceptable level of inter-rater reliability in the field setting. Future studies to measure construct and concurrent validity, test-retest reliability and responsiveness of the instrument are recommended as well as testing the instrument in different cultures. PMID- 7797320 TI - Pressure sores: impact on rehabilitation following surgically treated hip fractures. PMID- 7797321 TI - Rehabilitation practitioner competencies: some New Zealand data. PMID- 7797322 TI - Family response to paranoid and non-paranoid schizophrenic patients. PMID- 7797324 TI - The use of non-specific comments in a conversation aid for non-speaking people. PMID- 7797323 TI - Increasing the occupational level of a passive man through the employment of mentally handicapped peer caregivers. PMID- 7797325 TI - Effects of differential reinforcement, physical restraint and verbal reprimand on stereotyped body-rocking. PMID- 7797326 TI - Deaf people's perception of social interaction in working life. PMID- 7797327 TI - Preference for static or revolving cane tips by visually impaired travellers. PMID- 7797328 TI - Readiness for community residence: the AKIM-Jerusalem demonstration project. PMID- 7797329 TI - Basic models for disease occurrence in epidemiology. AB - BACKGROUND: One of the epidemiologist's most basic tasks is estimation of disease occurrence. To perform this task, the epidemiologist frequently models variability in disease occurrence using one of three distributions--the binomial, the Poisson or the exponential distribution. Although epidemiologists often use them and their properties appear in standard texts, we know of no text or review that compares and contrasts epidemiological application of these distributions. METHODS: In this commentary, we discuss these three basic distributions. We note key assumptions as well as limitations, and compare results from analyses based on each distribution. RESULTS AND CONCLUSIONS: We illustrate that the three distributions, although superficially different, often lead to similar results. We argue that epidemiologists should often obtain similar results regardless of which distribution they use. We also point out that application of all three distributions can be inappropriate if assumptions of independence or homogeneity of risks fail to hold. Finally, we briefly review how these basic distributions can be used to justify use of other distributions, such as the Gaussian distribution, for studying disease-exposure associations. PMID- 7797330 TI - Alcohol consumption and all-cause mortality. AB - BACKGROUND: Prospective studies of alcohol and mortality in middle-aged men almost universally find a U-shaped relationship between alcohol consumption and risk of mortality. This review demonstrates the extent to which different studies lead to different risk estimates, analyses the putative influence of abstention as a risk factor and uses available data to produce point and interval estimates of the consumption level apparently associated with minimum risk from two studies in the UK. METHOD: Data from a number of studies are analysed by means of logistic-linear modelling, taking account of the possible influence of abstention as a special risk factor. Separate analysis of British data is performed. RESULTS: Logistic-linear modelling demonstrates large and highly significant differences between the studies considered in the relationship between alcohol consumption and all-cause mortality. The results support the identification of abstention as a special risk factor for mortality, but do not indicate that this alone explains the apparent U-shaped relationship. Separate analysis of two British studies indicates minimum risk of mortality in this population at a consumption level of about 26 (8.5 g) units of alcohol per week. CONCLUSIONS: The analysis supports the view that abstention may be a specific risk factor for all cause mortality, but is not an adequate explanation of the apparent protective effect of alcohol consumption against all-cause mortality. Future analyses might better be performed on a case-by-case basis, using a change-point model to estimate the parameters of the relationship. The current misinterpretation of the sensible drinking level of 21 units per week for men in the UK as a limit is not justified, and the data suggest that alcohol consumption is a net preventive factor against premature death in this population. PMID- 7797332 TI - Regional and social class variation in the relative risk of death from amenable causes in the city of Helsinki, 1980-1986. AB - BACKGROUND: Relative risk of death from causes amenable to health services' intervention was studied in a case-control design to ascertain regional and social class differences. METHODS: The data were 2091 deaths from amenable causes and 8364 randomly drawn living controls in 1980-1986 in the seven health districts in Helsinki, Finland. Logistic regression was used to adjust relative risk estimates for age, sex and marital status. RESULTS: Adjustments decreased the risk ratios. Compared with the Southern District, the Middle District had significantly higher adjusted relative risk (RR = 1.4; 95% confidence interval [CI]: 1.1-1.7). People with no address had even higher relative risk (RR = 3.1; 95% CI: 2.3-4.2). Compared with social group I, increased relative risks were found in social group II (RR = 1.3; 95% CI: 1.1-1.6), group III (RR = 2.0; 95% CI: 1.6-2.4), group IV (RR = 1.9; 95% CI: 1.5-2.5) and group VI (RR = 8.5; 95% CI: 6.9-10.6). Males had higher relative risk than females (RR = 2.4; 95% CI: 2.1 2.8). Of the dead with no address, 29% were pensioners and 41% had been registered unemployed or occupation was unknown; 48% were single and 17% divorced. CONCLUSIONS: Our results suggest that regional inequalities in health care between various districts in Helsinki are small. However, to a large extent two overlapping groups, social group VI and people with no address, seem to delineate a deprived group likely to need special help from health care. PMID- 7797331 TI - Time trends in cause-specific mortality in Estonia from 1965 to 1989. AB - BACKGROUND: During the last 30 years, in most developed countries, life expectancy has increased considerably. In Estonia, over the past half century, health and social policy was dictated by the Soviet socioeconomic system. In order to evaluate the consequences to health and to evaluate trends in health, cause-specific mortality was studied in Estonia. METHODS: The study was based on national death records from 1965 to 1989. Mortality rates were computed for all causes of death combined and for 16 cause groups. Age-standardization (European population) was performed using 5-year age groups. RESULTS: From 1965-1969 to 1985-1989, the age-standardized mortality rate for all causes combined increased by 4.0% for males and decreased by 1.5% for females. The greatest increase was observed for ages 45-54 among males (26.3%) and for ages 55-64 among females (7.0%). Very high death rates from circulatory diseases and high mortality from injuries and poisoning are of specific concern, particularly for males. Mortality from circulatory diseases continues to rise for ages 45-74 among males and for ages 55-64 among females. Mortality rates for neoplasms and endocrine disorders are also increasing; however, the mortality rates from respiratory and infectious diseases have shown a substantial decrease. CONCLUSIONS: Chronic diseases, together with injuries and poisoning, remain a serious public health problem in Estonia. Preventive measures, including earlier detection of diseases as well as changes in social security and individual health behaviour are needed to improve the health of the population. PMID- 7797333 TI - Educational level of spouses and risk of mortality: the WHO Kaunas-Rotterdam Intervention Study (KRIS). AB - BACKGROUND: A 9.5-year follow-up of the Kaunas-Rotterdam Intervention Study (KRIS) provided the opportunity of investigating whether the educational level of wives was associated with their husbands' risk of mortality and coronary heart disease (CHD), independently of the educational level of the husbands themselves. METHODS: The data represent populations consisting of 2452 Lithuanian men and 3365 Dutch men. These men were extensively screened for cardiovascular risk factors in the period 1972-1974. During the follow-up 303 Kaunasians and 350 Rotterdammers died. We used the Cox proportional hazards and the logistic regression models to analyse the data. RESULTS: We found that men whose spouses had little education apparently had an increased risk of all-cause mortality, even when their own educational level was taken into account. The relative risks (RR) were 1.57 in Kaunas and 2.15 in Rotterdam. The results for fatal and non fatal myocardial infarctions were compatible with this finding, especially in Rotterdam. The prevalence of smoking was higher among men whose wives had primary schooling only. Nonetheless, adjusting the effect of the wife's educational level on her husband's mortality risk for all coronary risk factors in the husband only partially explained the association. CONCLUSIONS: The spouse's educational level appears to have independent effects on a man's risk of mortality in both eastern and western European communities. The results strongly suggest that including characteristics of the socioeconomic status of an individual's spouse would improve studies of socioeconomic differences in health. PMID- 7797334 TI - Risk factors for child mortality in northern Ghana: a case-control study. AB - BACKGROUND: A population-based case-control study was carried out to investigate potential risk factors for post-neonatal and child mortality in northern Ghana were child survival rates are among the lowest in Africa. METHOD: Cases were post neonatal infant and child deaths identified within a large population under continuous demographic surveillance. For each case, one living control, matched for age, sex and locality, was selected from the demographic database. Mothers of each case and control were interviewed to obtain information on social, enconomic, demographic, environmental and other possible risk factors. Matched analyses of the 317 cases and their controls were performed using discordant pairs analysis and conditional logistic regression. RESULTS: The mortality rate for children aged 6 months to 4 years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person (OR = 1.8, 95% CI: 1.0-3.2), if the preceding birth interval was < 24 months (OR = 2.2, 95% CI: 1.1-3.9), if the father beat the child's mother (OR = 4.3, 95% CI: 1.2-15.6) or if the water source was unprotected (OR = 1.6, 95% CI: 1.0-2.7). No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. CONCLUSIONS: Few strong risk factors for mortality were identified, perhaps because living conditions within the study population are relatively homogeneous. While mortality rates may be reduced by targeted interventions, such as increasing deliveries by trained people, more general improvements in the socioeconomic status in the region are essential. PMID- 7797335 TI - International comparisons of injury mortality in the elderly: issues and differences between New Zealand and the United States. AB - BACKGROUND: International comparisons of mortality rates for injury, as for other conditions, can suggest priorities for further research and intervention. However, variability in the assignment of underlying cause, especially among the elderly, may lead to difficulty in interpreting cross-national differences in death rates. Despite similarities between the two countries, the injury death rate for ages < or = 65 in New Zealand is substantially higher than the United States rate. The objective of this study was to investigate possible reasons for this difference. METHODS: We used data not previously reported for New Zealand to calculate the cause-specific injury death rates for ages > or = 65, compared them with US rates, and examined other injury rates that could help explain the observed difference. RESULTS: The New Zealand death rate from falls for ages > or = 65 was nearly three times the US rate (92 versus 32 per 100,000), causing the death rate for all injuries in this age group to be 34% higher in New Zealand (153 versus 114 per 100,000). However, hospitalization rates for both falls and hip fractures are similar for the two countries. CONCLUSIONS: The substantially higher fall injury death rates for older New Zealanders are not fully explained by differences in the incidence of falls resulting in injury nor the case fatality rate for fall-related injury. US injury death rates based on underlying cause of death might be similar to New Zealand rates, and thus substantially higher, if subjected to comparable procedures for the completion and coding of death certificates. As in studies of other conditions, international comparisons of injury death rates based on underlying cause, especially in studies of the elderly, must consider variation between countries in death certification and coding practices. PMID- 7797336 TI - Tornado injuries related to housing in the Plainfield tornado. AB - BACKGROUND: On 28 August 1990, a tornado in Will County, Illinois, caused 29 deaths and more than US $200 million in damage. Risk factors for impact-related morbidity and mortality were studied. METHODS: A case-control study was conducted of 26 people hospitalized or killed, and 116 injured, randomly selected people who were in houses damaged by the tornado. To obtain information on study subjects, telephone interviews were conducted, and hospital records, coroners' reports, and American Red Cross records were abstracted. Structural details on houses were collected from tax assessor records. RESULTS: Cases were more likely than controls to have been in multistorey houses than in single-storey houses (OR = 3.9; 95% CI: 1.2-13.2). The risk associated with houses built after 1972 (OR = 7.9) and those built from 1962 to 1972 (OR = 2.2) was greater than for those built before 1962 (OR = 1.0; chi 2 for trend = 12.1; P < 0.01). Being in the basement when the tornado hit was protective (OR = 0.1; 95% CI: 0.0-0.4). CONCLUSIONS: One-storey houses were safer than multistorey houses, and basements were safer than other rooms. The association of risk with the construction date of the house is a new finding and should be examined in further studies. PMID- 7797337 TI - A non-invasive measure of photoageing. AB - BACKGROUND: Photoageing develops in skin due to chronic sun exposure and a method of measuring photoageing would be useful in monitoring solar damage in populations, in studies of sun exposure as an aetiological agent, and in the evaluation of the effects of cosmetics and therapeutics. Methods of measuring photoageing include several invasive techniques as well as non-invasive techniques which are often difficult to use and have not been validated. The non invasive measure of photoageing described here is a new method for grading silicone-rubber casts of the skin surface. This paper describes the development of the measure (named the sigma system) and compares its reliability and validity with the most widely-used similar measure (the Beagley and Gibson system). METHODS: Useable punch biopsies and silicone-rubber casts were obtained from 82 subjects. Two random subgroups of silicone casts were created and the first subgroup was used for the development of the sigma system, while the second subgroup was used to test validity. All casts were graded twice using the sigma system and twice using the Beagley and Gibson system by two observers. The gradings of the second subgroup of casts were compared with the degree of photoageing seen on histological examination of the biopsies. RESULTS: The intraclass correlation coefficient (ICC) for inter-observer reliability of the sigma system was 0.89, with 73 of the 82 casts graded at the same level of photoageing by the two observers. Intra-observer ICC were 0.84 and 0.87 for the two observers. The Goodman-Kruskal tau for agreement between the grade on the sigma system and histological degree of photoageing was 0.22. While these values are very similar to the reliability and validity estimates obtained using the Beagley and Gibson system, the sigma system is easier to learn and to use. CONCLUSIONS: The sigma system is a reliable and easy-to-use measure of photoageing which has many possible applications in monitoring and studying the effects of solar exposure. PMID- 7797339 TI - Misclassification of social disadvantage based on geographical areas: comparison of postcode and collector's district analyses. AB - BACKGROUND: Analysis of socioeconomic status (SES), defined on the basis of geographical area, will always be subject to misclassification of individuals. We studied the relationship between SES and selected health-related measures when SES was defined firstly on the basis of postcode and secondly on the basis of the smaller spatial area of collector's district (CD). METHOD: A Census population of 1.4 million was used to investigate the misclassification of individuals to SES group using postcode as opposed to CD. A field survey of 1000 respondents and a mortality register of 1756 deaths were used to compare the relationship between SES and certain outcome variables, when SES group was assigned using postcode and CD. Misclassification probability matrices were used to try to adjust the postcode-based results to approximate CD-based results. RESULTS: The Census data showed that nearly 50% of residents were misclassified into SES groups by the postcode-based system compared with a CD-based system. In comparing the most socially disadvantaged group with the least disadvantaged group, the postcode analysis underestimated the absolute effects of SES by 58% for the increased prevalence of smoking, by 19% for the reduced prevalence of participation in junior sporting clubs and by 13% for the increased mortality rate at ages 0-64 years. Adjustment of postcode-based results using misclassification matrices proved fruitless due to differential misclassification and technical difficulties. CONCLUSIONS: Misclassification of individuals to SES groups on the basis of postcode has caused an underestimation of the true relationship between SES and health-related measures. A reduction of this misclassification by using smaller spatial areas, such as CD or census enumeration districts, will provide improved validity in estimating the true relationship. PMID- 7797338 TI - Nutritional change and economic crisis in an urban Congolese community. AB - BACKGROUND: In 1986, the government of Congo undertook a structural adjustment programme to cope with the economic crisis. We present the results of a study whose objectives were to assess the evolution of nutritional status of an urban community between 1986 and 1991 and to identify specific groups for which the nutritional status may have worsened. METHODS: Two cross-sectional surveys were carried out on representative samples of Brazzaville children < 6 years old: 2295 children were surveyed in 1986 and 2373 in 1991. Anthropometric assessment of nutritional status was performed. For children, weight-for-height and height-for age indices were used according to WHO recommendations. Wasting and stunting were respectively defined as indices under -2 z-scores. Body mass index of mothers was calculated and risk of chronic energy deficiency (CED) was defined as < 18.5 kg/m2. Socioeconomic data relative to the households were also collected. Multivariate statistical methods were used to obtain adjusted estimates of nutritional changes in the community. RESULTS: Data analysis led to several converging results: increase in the percentage of low birthweight (10.2% in 1985 versus 18.7% in 1990), increase in the percentage of CED (from 7.9% to 10.5%), and increase in the prevalence of wasting (from 2.9% to 4.2%). By contrast, the overall prevalence of stunting decreased from 13.9% to 11.0%. After statistical adjustment, the factors found to influence the evolution of anthropometric status were: age of child, age of mother, schooling of mother and household characteristics such as number of preschool children, economic level and head of household's occupation. CONCLUSIONS: The study enables the negative effects of the economic crisis to be quantified. Body mass index is shown to be sensitive to economic changes. It could be recommended as a possible indicator for monitoring the nutritional status at population level. The results also call for a new impetus in preventive health programmes and the implementation of nutritional surveillance activities. PMID- 7797341 TI - Prognostic models and the propensity score. AB - Subjects in observational studies of exposure effects have not been randomized to exposure groups and may therefore differ systematically with regard to variables related to exposure and/or outcome. To obtain unbiased estimates and tests of exposure effects one needs to adjust for these variables. A common method is adjustment via a parametric model incorporating all known prognostic variables. Rosenbaum and Rubin propose adjustment by the conditional exposure probability given a set of covariates which they call the propensity score. They show that, at any value of the propensity score, covariates are on average balanced between exposure groups. Thus matching on the propensity score leads to unbiased estimators and tests of exposure effect. However, the validity of the method depends on knowing the exposure probability. This quantity is usually not known in observational studies and needs to be estimated. PMID- 7797340 TI - Application of Markov process modelling to health status switching behaviour of infants. AB - BACKGROUND: This study is an attempt to apply Markov process modelling to health status switching behaviour of infants. The data for the study consist of monthly records of diagnosed illnesses for 1152 children, each observed from the month of first contact with Kasangati Health Centre, Kampala, Uganda, until age 18 months. METHODS: Only two states of health are considered in the study, a 'Health' state, denoted by W: (for Well), and an 'Illness' state denoted by S: (for Sick). The data are thus reduced to monthly records (W or S) of the states of health of the study sample. The simplest model of dependence of current health state on the past is one that links the current state to the immediately preceding month only; that is a Markov model. The starting point of this study was therefore to determine the proportions of children making the transitions W-->W, W-->S, S-->W, S-->S, from one month to the next, for each month from birth (month 0) to 18 months of age (month 18). These were used as estimates of the probabilities of making these transitions for each month from birth. This paper discusses the main features emerging from the study of these transition probabilities. RESULTS: In the first 5 months after birth, the probabilities of making the transitions W- >W, W-->S, S-->W, S-->S from one month to the next, showed some dependence on the age of the child. From the sixth month on, however, the dependence on age seemed to wear off. The transition probabilities remained the same from then on, suggesting that the switching pattern between health states behaves, eventually, like a time-homogeneous Markov Chain. This time-homogeneous chain attained a steady state distribution at about 12 months from birth. CONCLUSIONS: The study has shown that the transitions between Health and Illness for infants, from month to month, can be modelled by a Markov Chain for which the (single-step) transition probabilities are generally time-dependent or age-dependent. After the first few months of life the dependence on age may wear off, as in this study, leading to a time-homogeneous Markov Chain, which eventually attains a steady state distribution in about 12 months. Interpretations of the transition probabilities as measures of disease prevalence are discussed. PMID- 7797343 TI - Combined oral contraceptives and risk of cervical carcinoma in situ. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. AB - BACKGROUND: Although the possible influence of oral contraceptives on risk of cervical carcinoma in situ has been the subject of multiple prior investigations, the results have been inconsistent. METHODS: Data from a multinational, collaborative case-control study were analysed to investigate further this possible relationship. To assess potential screening bias, some statistical analyses were restricted to subgroups of cases with and without symptoms at the time of their diagnosis. RESULTS: Relative risk estimates in relation to various features of oral contraceptive use tended to be highest for asymptomatic disease, lowest for disease presenting with vaginal bleeding, and intermediate for disease presenting with other symptoms, suggesting the presence of a screening bias. In women with vaginal bleeding, who are least likely to have been detected by routine screening, no elevated risk of cervical carcinoma in situ was observed in relation to ever having used combined oral contraceptives, but there was an increased risk in users of over 60 months' duration. An increasing trend in risk with duration of use was most pronounced in these women who first used oral contraceptives in the past 5-10 years; and in women who used oral contraceptives for more than 60 months, risk declined with time since last use. CONCLUSION: These findings could reflect a reversible effect of long-term use of oral contraceptives at an intermediate stage in the carcinogenic process, or a non causal relationship due to unidentified sources of bias or confounding. PMID- 7797342 TI - Modelling AIDS reduction strategies. AB - BACKGROUND: Mathematical models of the AIDS epidemic have not been able to give accurate predictions about the size of the epidemic because it is not possible to obtain sufficiently accurate measurements of the factors that enable HIV transmission. The uncertainties inherent in models of the AIDS epidemic appear to limit their relevance to epidemiologists. However, it is shown here that the uncertainties need not prevent models being used to make reliable decisions about which preventive strategy will be most effective. METHOD: A range of strategies are simulated in a model of the AIDS epidemic. The simulations are repeated as the value of what seems to be the most important uncertain factor, is varied. The effect of this variation on the effectiveness of each strategy is noted. In principle, the process could be repeated whilst all other uncertain factors are varied as well. RESULTS: Although varying one uncertain factor created enormous variation in the size of the epidemic, it is remarkable that for most preventive strategies the relative effectiveness of the strategies was barely altered. Hence for the most part the ranking of strategies in order of effectiveness is not affected by the area of uncertainty explored here. The results also highlight the potential effectiveness not only of general condom promotion, but also the use of circumcision and spermicides and general screening or targetted screening in sexually transmitted disease clinics. CONCLUSIONS: Epidemiological modelling may accurately rank the effectiveness of interventions although it may fail to predict the size of the epidemic. PMID- 7797344 TI - Evidence of serological cross-reactivities with human immunodeficiency virus types 1 and 2 and human T-lymphotropic virus types I and II in sera of pregnant women in Ibadan, Nigeria. AB - BACKGROUND: Our previous studies have indicated that the human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV) groups of retroviruses are endemic among various populations in Nigeria. These viruses are antigenically distinct and antibodies to HIV and HTLV do not cross-react, so we studied the prevalence of HIV-1, HIV-2, HTLV-I and HTLV-II antibodies in sera of pregnant women attending an antenatal clinic in Ibadan, Nigeria. METHODS: In all, 364 sera were screened using three different enzyme immunoassays, including those that distinguished HIV-1 antibodies from HIV-2, and HTLV-I antibodies from HTLV-II. All repeatedly reactive sera were confirmed by Western blots and synthetic peptide assays for the respective viruses. RESULTS: Overall, 71 sera (19.5%) had antibodies to HIV, HTLV or both groups of retroviruses. Most (95.8%) of the reactive samples were from women 20-29 years old. Two of five sera from individuals < 20 years old reacted for HIV antibodies while one serum from a 40 year old woman was reactive for HTLV-I antibodies. Of the 71 reactive sera, 29 (8%) had antibodies to HIV (HIV-1 = 14, HIV-2 = 9, HIV-1/2 = 6) and 42 samples (11.5%) showed antibodies to HTLV (HTLV-I = 20, HTLV-II = 14, HTLV-I/II = 8). Seven of 71 seropositive samples (9.8%) reacted for both HIV and HTLV antibodies in various combinations, including one serum that showed antibody reactivities to all four retroviruses (i.e. HIV-1, HIV-2, HTLV-I and HTLV-II). CONCLUSIONS: The high prevalence of antibodies to subtypes of the two entirely distinct retrovirus groups in young women has important implications for defining epidemiological patterns of diseases associated with co-infections with two or more retroviruses. PMID- 7797345 TI - Epidemiology and control of infant and early childhood malaria: a competing risks analysis. AB - BACKGROUND: Against increasing malaria problems in most tropical countries, very little is known about the socio-epidemiological determinants of this condition. METHODS: Using extensive information on a representative sample of 9774 newborns followed for 2 years and multi-state hazards models, this study investigates jointly the determinants of paediatric mortality from malaria and other causes. RESULTS: Malaria contributes to one out of every 10 infant deaths. Malarial mortality covaries with dwelling conditions, antenatal care attendance, parity, infant feeding practices, intercurrent infections, and child's immunization status. Lack of antenatal care, lack of immunization in childhood and sub standard living conditions of overcrowding are the major risk factors of malarial and non-malarial mortalities, even after correcting for unobserved heterogeneity. CONCLUSIONS: These findings suggest that the impact of malaria on infant and early childhood health and survival might be much more important than usually thought. Antenatal care attendance, improved housing conditions and childhood immunization practices are potentially cost-effective strategies for malaria control. The competing risks analysis formulated here is offered as a suitable means of analysing cause-specific mortality differentials. PMID- 7797346 TI - An outbreak of hepatitis A among homosexual men in Amsterdam, 1991-1993. AB - BACKGROUND: When in August 1992 it became evident that an outbreak of hepatitis A virus infections (HAV) was taking place in the male homosexual community in Amsterdam a case-control study was conducted to validate the assumption that the outbreak was associated with sexual practices involving oro-anal and digital-anal contact and frequent visits to gay saunas and darkrooms. METHODS: In all, 37 cases reported to the Amsterdam Municipal Health Service (AMHS) in the period December 1991 to March 1993 and 68 anti-HAV negative controls completed an anonymous questionnaire concerning the practice of different sexual techniques and the number of visits to gay saunas and darkrooms in the 2 months preceding the onset of illness or date of interview. Controls were recruited from healthy homosexual men participating in a prospective study on HIV/AIDS conducted by the AMHS. RESULTS: In univariate analysis a statistically significant association was found between visits to gay saunas and darkrooms, the number of visits to these locations (OR = 8.2) and HAV infection. In the logistic regression analysis the association for visits to saunas and darkrooms remained significant (OR = 10) whereas high-risk sexual techniques could not be included in the model. CONCLUSIONS: These results indicate that to prevent future outbreaks of HAV in male homosexuals in Amsterdam there is a need to stress in the 'safe sex' campaigns, directed at the prevention of HIV infection or in additional campaigns, the prevention of other sexually transmitted disease including HAV infection with emphasis on routes associated with certain sexual techniques and on visits to gay saunas and darkrooms. PMID- 7797348 TI - Helicobacter pylori infection in rural settlements (Kibbutzim) in Israel. AB - BACKGROUND: Helicobacter pylori (HP) is accepted as a major cause of type B gastritis, which is strongly associated with peptic ulcer disease. Epidemiological studies have indicated a correlation of HP infection and socioeconomic class. METHODS: To determine the prevalence of HP infection and to evaluate symptoms and risk factors associated with HP infection in a rural population, 377 asymptomatic individuals were studied out of a random sample of 453 people. Subjects were randomly chosen in a ratio of 1:4 of all the adults over 30 years, living in eight communal settlements in Israel. Blood samples were taken and subjects answered a questionnaire in which sociodemographic information, clinical gastrointestinal background and the use of medication were included. A sensitive enzyme-linked immunoassay was used to determine antibodies to HP in serum. RESULTS: The overall prevalence of HP infection was 72%. In a multivariant discriminant analysis: age, country of origin and ethnic group were found to be the most closely associated variables for HP infection and the discriminant analysis succeeded in predicting correctly, in 62% of the population, whether they had or did not have HP infection. There was no significant difference with gender, occupation, educational level, blood group, smoking, gastrointestinal symptoms and use of medication. CONCLUSIONS: The prevalence of HP infection was higher than that in industrialized countries, but lower than in developing countries. The prevalence in a rural population was slightly higher than that of an urban population in Israel (65%). The country of origin and ethnic group influenced the prevalence of HP infection and not birth and growing up on the Kibbutz. PMID- 7797349 TI - Age-standardization in epidemiological data. PMID- 7797347 TI - Respiratory virus antibodies in adults of a Norwegian community: prevalences and risk factors. AB - BACKGROUND: The aims were to examine prevalences as well as demographic and environmental predictors of respiratory virus antibodies in serum. METHODS: In a cross-sectional study of 18-73 year old Norwegian adults a random stratified sample (n = 1512) was invited to attend an examination at an outpatient clinic. Seven respiratory virus antibodies were assessed by the complement fixation test. RESULTS: The attendance rate was 84%. The most frequent virus antibodies with titre of > or = 1:8 were influenza virus type A with a population standardized prevalence of 44%, adenovirus 25% and influenza virus type B 22%. The prevalences of antibodies against parainfluenza virus type 1, 2 and 3 increased with age. Smokers compared to non-smokers had an adjusted odds ratio (OR) of 1.7 (95% confidence interval [CI]: 1.3-2.4) for having one or more of the seven examined virus antibodies. The presence of one or more of the virus antibodies increased from summer to winter months (adjusted OR = 1.3 per month; 95% CI: 1.2-1.4) and it was higher in occupational dust or gas exposed smokers (adjusted OR = 2.0; 95% CI: 1.1-3.7) compared with unexposed smokers. CONCLUSIONS: Ageing, smoking, occupational dust or gas exposure as well as season of the year may thus be predictors for levels of respiratory virus antibodies in adults. These observations should be taken into account when comparing prevalences of virus antibodies in various communities as well as when examining the relationship between presence of virus antibodies and airway disease. PMID- 7797350 TI - Age-standardization in epidemiological data. PMID- 7797351 TI - Coffee and blood lipids in women. PMID- 7797352 TI - Excess female fatalities among patients with meningococcal disease. PMID- 7797353 TI - Infant breastfeeding and the risk of childhood lymphoma and leukaemia. AB - BACKGROUND: A protective effect of breastfeeding on childhood lymphoma has been indicated but supportive evidence is limited. METHOD: Data from a population based case-control study of childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukaemia cases and their age- and sex-matched community controls, were analysed. RESULTS: After adjustment for potentially confounding variables, a slight, although non-significant, reduction in risk of lymphoma was observed among children who were breastfed as infants versus those who were not (odds ratio [OR] = 0.69; 95% CI: 0.3-1.7). The reduction was somewhat greater for children who had been breastfed longer and appeared to pertain primarily to Hodgkin's disease and to cases diagnosed before the age of 6 years. As expected, there was no reduction in risk of acute leukaemia associated with breastfeeding. CONCLUSIONS: Although providing neither strong support for nor refuting the study hypothesis, these data suggest that if breastfeeding does reduce the risk of lymphoma, its protective effect among Chinese children is likely modest in magnitude and concentrated in certain subgroups defined by length of breastfeeding, age at diagnosis and histological subtype of cancer. PMID- 7797354 TI - Dietary factors and stomach cancer: a case-control study in Korea. AB - BACKGROUND: Stomach cancer is the most common cancer among Koreans. There is wide agreement that dietary factors are important in gastric carcinogenesis, but the role of many Korean food items remains unknown. METHODS: A case-control investigation involving 213 incident cases of histologically confirmed stomach cancer and an equal number of controls, matched by age (within 2 years) and sex, was conducted from June 1990 to October 1991. RESULTS: An increased risk of stomach cancer was noted among those with high consumption of stewed foods such as soybean paste stew and hot pepper-soybean stew, broiled fish, and those who liked salty food. However, mung bean pancake, tofu (soybean curd), cabbage, spinach, and sesame oil decreased the risk of stomach cancer. Stratified analysis by salt in combined foods, such as stewed foods and pickled vegetables, disclosed salt as being an important risk factor. Analysis of cooking methods showed that broiling and salting increased the risk of stomach cancer, but that frying tended to decrease the risk. These results suggest that the cooking method might modify the gastric carcinogenicity of foods. As non-dietary factors, smoking and a family history of stomach cancer increased the risk, but use of a refrigerator decreased the risk of cancer. CONCLUSIONS: Heavy salt consumption and cooking methods like broiling and salting seem to play a major role in gastric carcinogenesis among Koreans. PMID- 7797355 TI - A case-control study of physical activity in relation to risk of cancer of the right colon and rectum in men. AB - BACKGROUND: Epidemiological data suggest that physical activity is modestly or moderately protective against colorectal cancer. Additional data are needed to define better the slope of the dose-response curve and to clarify the types of activities that appear most protective. METHODS: We examined the relation between occupational and vigorous leisure time physical activity and risk of cancer of the right colon and rectum in data from a case-control study conducted in New England from 1986 to 1988. We interviewed 163 cases with cancer of the right colon, 242 cases with cancer of the rectum, and 703 community controls. RESULTS: Vigorous leisure time physical activity was associated with a decreased risk of cancer of the right colon; for men exercising > or = 2 hours per week the odds ratio was 0.60 (95% confidence interval [CI]: 0.35-1.00) compared with those who did not exercise. Adjustment for potentially confounding factors, including diet, had essentially no effect on the association. Self-reported occupational activity was less strongly related to risk of right colon cancer; the odds ratio for heavy work was 0.70 (95% CI: 0.32-1.51). Occupational activity coded according to job title was essentially unrelated to risk of right colon cancer. An association between physical activity and decreased risk of rectal cancer was not present in these data. CONCLUSIONS: Our data add weight to the evidence that physical activity is related to decreased risk of colon cancer. PMID- 7797356 TI - Occupation, smoking and demographic factors, and renal cell carcinoma in Germany. AB - BACKGROUND: The role of occupational exposure in the aetiology of renal cell cancer is still not clear. In a population-based, case-control study we investigated occupational and smoking history as well as place of residence, marital and socioeconomic status. METHOD: In a case-control study in Germany, 277 adult cases with incident renal cell cancer and 286 controls frequency-matched to the cases for age and gender have been interviewed. The data were analysed by standard methods using unconditional logistic regression models, to estimate the relative risk (RR) and the corresponding 95% confidence interval (95% CI). RESULTS: Socioeconomic status was inversely associated (RR = 0.61, 95% CI: 0.3 1.2 for highest category) with the risk for renal cell cancer. Heavy smoking gave an increased, but not significant (about twofold) RR in men and women for ex smokers and current smokers. Employment in metal-related industries (RR = 1.63, 95% CI: 1.1-2.5) was also identified as a risk factor. Additionally, we found an elevated risk associated with exposure to perchloroethylene and tetrachlorocarbonate (RR = 2.52, 95% CI: 1.2-5.2) but no time trend could be observed. No associations were found for other occupational exposures, such as working in the chemical industry, transportation or farming nor for exposure to pesticides. CONCLUSIONS: The results of our study lead to the suggestion that smoking, occupation and demographic factors probably play a minor role in the aetiology of renal cell cancer. PMID- 7797357 TI - Long-term prognosis of different forms of coronary heart disease: the Reykjavik Study. AB - BACKGROUND: While coronary heart disease (CHD) is a serious and often fatal disease the prognosis is variable and major effort has been invested in risk stratification. The purpose of this study was to examine the relation between long-term prognosis and risk factors in different clinical categories of CHD. METHODS: A general population sample of 9141 men, aged 34-79 at entry into the study was divided into six groups with respect to manifestations of CHD at entry: I. Symptomatic infarction. II. Silent or unrecognized infarction. III. Angina pectoris with ischaemic changes on ECG. IV. Angina without ischaemic changes. V. Angina by Rose questionnaire but not confirmed by a physician. VI. No manifestations of CHD. RESULTS: The risk factor profile varied considerably between the different categories and by life-table analysis marked differences in survival were demonstrated between the groups. The risk factors maintained their detrimental effects on prognosis in the presence of CHD. Thus, age, serum total cholesterol, impaired glucose tolerance and smoking were found by Cox's regression to be statistically significant independent risk factors of CHD mortality among men having manifestations of CHD (groups I-V). Furthermore, the composite risk score, a measure of the overall risk factor exposures had marked effect on the prognosis of the various CHD groups. When the comprehensive risk factor score for both CHD mortality and all-cause mortality was accounted for marked differences persisted in the long-term prognosis. Compared to those without CHD the infarct groups had about a 7.6- and 3.7-fold risk of dying from CHD and all causes respectively. Those with angina had from 2.5- to 3.2-fold risk of CHD mortality and 1.7- to 2.2-fold risk of all-cause mortality depending on the subgroup of angina, again compared to those without manifestations of CHD. CONCLUSION: Different categories of CHD had different risk factor profiles and the long-term prognosis resulted from a complex interplay between those factors and the diagnostic category of CHD. The risk factors maintained their detrimental effects on prognosis in the presence of CHD and after accounting for the comprehensive risk factor score marked differences persisted in the long-term prognosis, being worst for those having suffered a myocardial infarction, either symptomatic or silent. PMID- 7797358 TI - Longitudinal development of lipoprotein levels in males and females aged 12-28 years: the Amsterdam Growth and Health Study. AB - BACKGROUND: In the Amsterdam Growth and Health Study, the longitudinal development of risk factors for coronary heart disease (CHD) was investigated. METHODS: Serum cholesterol (TC), high density lipoprotein (HDL) and the TC/HDL ratio were measured at the ages of 13, 14, 15 and 16 years (adolescence) and at the ages of 21 and 27 years ([young] adulthood). RESULTS: No cohort, time of measurement, drop-out or test/learning effects were found for TC, HDL and the TC/HDL ratio. For males the longitudinal development of TC showed a dip in the adolescent period, while females showed constant values. For both males and females TC values increased during young adulthood, but females had higher (P < or = 0.001) absolute values than males. The HDL values for males decreased throughout the measurement period, while for females a stable period during adolescence was followed by a slight increase during adulthood. For the TC/HDL ratio males showed an increase during young adulthood, while females stayed more or less constant over the whole measurement period. The percentages of subjects above (or below for HDL) objective risk values increased with age: from 0% to 1% during adolescence to 11% (males) and 14% (females) for TC, 5% (males) and 1% (females) for HDL and 13% (males) and 1% (females) for the TC/HDL ratio. CONCLUSIONS: In a relatively young and healthy population TC and TC/HDL values tended to rise with age (especially in males) indicating that prevention related to these risk factors for CHD should start early in life. PMID- 7797360 TI - Cancer mortality in migrant populations within Italy. AB - METHODS. Mortality rates for four types of cancer (stomach, colorectal, lung, and breast cancer) in migrant populations were compared to those of individuals who still resided in the political region in which they were born. The effects on mortality rates of place of birth and of place of residence were studied, comparing different regression models. RESULTS. Overall, people who were born in the South and who later migrated had significantly higher mortality rates than the southern population, but lower than the population in the area of residence, for most cancers. Place of birth and place of residence showed different power in explaining the observed mortality rates for different cancer sites: place of birth was a stronger predictor for stomach and breast cancers, while residence was a stronger predictor for lung and colorectal cancers. The status of 'migrant' was found to be an overall risk factor. The compatibility of the results obtained with different aetiological hypotheses is discussed. PMID- 7797359 TI - Pubertal serum lipoprotein (a) and its correlates in Belgian schoolchildren. AB - BACKGROUND: Serum lipoprotein (a) (Lp(a)) is an independent risk factor for premature coronary artery disease in Caucasians. Generally Lp(a) serum levels remain fairly constant throughout an individual's life, but are presumably modulated by sex hormones. This study documents the distribution and correlates of serum Lp(a) during sexual maturation in Belgian children. A comparison with Lp(a) levels in Belgian adults is made. METHODS: Serum Lp(a), lipid and apolipoprotein A-I and B levels were determined cross-sectionally in 266 Belgian schoolchildren and adolescents in relation to sexual maturation, anthropometrics and socioeconomic status. Sexual maturity was scored according to Tanner's classification. RESULTS: Median Lp(a) levels were 82, 117, 110, 100 and 73 mg/l at the five subsequent genital development stages in boys (ANOVA, P = 0.816), and 73, 78, 204, 110 and 114 mg/l at the five breast development stages in girls (ANOVA, P = 0.087). The Lp(a) distributions in boys and girls were skewed to the right, overall medians being 82 and 94 mg/ml (P = 0.2537). The 90th and 95th percentiles were 515 and 712 mg/l respectively. The geometric Lp(a) mean in children was significantly higher compared to that in 683 sex-matched Belgian adults (89 mg/l versus 69 mg/l, P = 0.006). Multiple linear regression pointed out that developmental age, chronological age, body mass index and/or systolic blood pressure predicted serum lipid and apolipoprotein levels, but none of the Lp(a) variance. CONCLUSION: Pubertal stage was not correlated with Lp(a) levels in Belgian schoolchildren, supporting the contention that serum Lp(a) is predominantly genetically controlled. PMID- 7797361 TI - Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months. AB - BACKGROUND: The methods currently used for measuring environmental tobacco smoke (ETS) exposure among small children all have their limitations. The aim of this study was to compare the results of questionnaire assessments of children's ETS exposure with cotinine measurements in urine and nicotine measurements in hair, a new method for estimating average ETS exposure. METHODS: Questionnaire information on ETS exposure and a sample of hair were collected from 94 children aged 12-36 months. A urine sample for cotinine analysis was obtained from 72 of the children. RESULTS: Nicotine was found in all hair samples and cotinine in all urine samples. Compared to children registered as unexposed by the questionnaire, hair nicotine levels were 12.4 times higher among children exposed to more than 10 DNC (daily number of cigarettes) (P < 0.001) and 3.6 times higher among children exposed to 1-10 DNC (P < 0.001). The median cotinine creatinine ratio (CCR) was 2.4 times higher among children exposed to more than 10 DNC compared to unexposed children (P < 0.001). No significant difference in median CCR was found between unexposed children and children exposed to 1-10 DNC. The correlation coefficient was 0.64 between children's hair nicotine levels and DNC, 0.50 between CCR and DNC and 0.56 between children's hair nicotine levels and CCR. CONCLUSION: Nicotine measurement in hair is a practical and valid method for estimating average ETS exposure in children. An underreporting of ETS exposure was indicated. PMID- 7797363 TI - Tubulovesicular elements in Blastocystis hominis from the caecum of experimentally-infected rats. AB - By transmission electron microscopy (TEM), tubulovesicular elements were seen in Blastocystis hominis obtained from the caecum of experimentally-infected rats. These appeared to arise from the peripheral cytoplasm and were rounded, oval or elongate in sections. It is suggested that these elements form a network for transfer of nutrients to the periphery during the process of encystation. PMID- 7797364 TI - Echinococcus multilocularis protoscoleces and hepatic cell activity in vitro. AB - E. multilocularis protoscoleces were co-cultured with hepatic cells in the presence of IAR 20 or BALB/c 3T3 cells. Hepatocyte activity was determined by assaying transferrin and albumin secretion in culture media. The level of these 2 plasma proteins is higher in hepatic/BALB/c 3T3 co-culture medium. In the presence of parasites, the transferrin level is unchanged while the production of albumin is stimulated during the first 48 h. Our results suggest that the albumin production could be attributed to a complex cellular cooperation between hepatocytes and activated Kupffer cells as previously observed in the acute inflammatory reaction. PMID- 7797365 TI - Comparison of the course of infection with Giardia muris in male and female mice. AB - The infection with Giardia muris in male and female C57BL/6 mice was characterized by enumerating cyst release in the feces and trophozoite burden in the small intestine. Cyst release differed between males and females during the course of the primary and challenge infections. Males and females released similar numbers of cysts in the feces during the acute phase of the infection. However, the trophozoite burden was significantly higher in males during the same period. Males released cysts in their feces longer than females and trophozoites present in their intestines for a longer period than females. From day 18 of infection the females did not release cysts in their feces, while males continued to do so for at least 60 days. Thus, distinct differences exist between male and female mice in their ability to harbor and eliminate this intestinal parasite. PMID- 7797362 TI - Chronic bronchitis and the type of cigarette smoked. AB - BACKGROUND: Smoking is a well known primary risk factor for chronic bronchitis. However, little is known about the relationship between different types of cigarettes smoked and chronic bronchitis. OBJECTIVE: To determine the association between chronic bronchitis and the type of cigarette smoked. METHODS: A cross sectional prevalence study was conducted in an urban area (Pelotas) of Southern Brazil. A total of 1053 subjects aged > or = 40 years were interviewed about respiratory symptoms and some risk factors for chronic bronchitis. RESULTS: After adjustment for confounding factors, the number of daily cigarettes smoked was strongly associated with the risk of chronic bronchitis (odds ratio [OR] = 8.10, 95% CI: 4.46-14.71 for smokers of > or = 20 cigarettes per day compared to non smokers). Among smokers, maize leaf cigarettes showed the highest risk (OR = 5.43 compared to non-smokers, 95% CI: 2.65-11.13) and filter cigarettes the lowest (OR = 2.19, 95% CI: 1.19-4.03). CONCLUSIONS: In addition to the number of cigarettes smoked, the use of maize leaf cigarettes was shown to have an important independent association with chronic bronchitis. PMID- 7797366 TI - Dictyocaulus viviparus: nucleotide sequence of Dv3-14. PMID- 7797367 TI - The fatty acids of each lipid fraction and their use in providing energy source of the plerocercoid of Spirometra erinacei. AB - The fatty acid concentration of each lipid fraction of plerocercoids of Spirometra erinacei and the host snake serum was investigated. The major fatty acids of phospholipid of the plerocercoids were C18:1, C18:0 and C16:0, and those of the host snake serum were C16:0, C18:1 and C18:0, in order of amount in both cases. The changes of the fatty acid composition of phospholipid of the plerocercoids when they were incubated in physiological saline at 18 degrees C and at 37 degrees C for 24 h were investigated in both cases. Polyunsaturated fatty acids increased at 18 degrees C, and saturated fatty acids increased at 37 degrees C. Michaelis constants (Km) of beta-hydroxyacyl-CoA dehydrogenase (HAD), NADH: ubiquinone oxidoreductase (complex I) (NADH: ferricyanide reaction) and complex I (NADH: ubiquinone reaction) for NADH were 20.6, 50 and 13.3 microM, respectively. The ATP production in mitochondria of the plerocercoids was accelerated by adding ADP and inhibited by adding such electron transport system inhibitors as rotenone, antimycin A and sodium cyanide. These results suggested that the fatty acids in the plerocercoids played an important role in regulating the fluidity of membrane by changing the composition in membrane lipid corresponding with the change of temperature circumstance. The NADH reduced by HAD might be accepted by the complex I in the electron transport system, and thus the parasites were capable of ATP production in a classical pathway of the oxidative phosphorylation system. PMID- 7797369 TI - Effects of haemagglutination (lectin) inhibitory sugars on Theileria parva infection in Rhipicephalus appendiculatus. AB - We have previously described the presence of haemagglutinins in tissues of the tick, Rhipicephalus appendiculatus and determined their sugar specificities by inhibition experiments. In this study, haemagglutination inhibitory sugars are shown to have an effect in vivo on the abundance of Theileria parva infected salivary gland acini in Rhipicephalus appendiculatus. A significant increase (P < 0.05) was observed in T. parva acinar infection rates in the salivary glands of R. appendiculatus fed on ears of rabbits infused with melibiose and raffinose. In contrast, mannose and turanose (non-haemagglutination inhibitory sugars) did not cause elevation of T. parva acinar infection rates. The effect of melibiose in elevating acinar infections was observed when used only during T. parva maturation in the salivary glands but not during parasite pick-up from an infected bovine host. Stabilates produced from ticks with elevated acinar infections did not differ from control stabilates in infectivity to cattle, by comparison of prepatent periods to pyrexia, or parasitosis, or in the severity of reactions. PMID- 7797370 TI - Histopathology of cultured sea bass (Lates calcarifer) (Centropomidae) infected with Cruoricola lates (Trematoda: Sanguinicolidae) from Pulau Ketam, Malaysia. AB - Cruoricola lates are found throughout sea bass (Lates calcarifer), most commonly in the mesenteric blood vessels, kidney, pericardial vessels, and eye. Eggs of C. lates were predominantly found in the gills, ventricle, hepatopancreas, and kidneys, but only develop to miracidia regularly in the gills and heart. Single miracidia escaping appear to cause little damage, but groups induce an inflammatory response and haemorrhage. Endocardial macrophages encapsulate eggs trapped between trabeculae in the heart. The reaction to eggs in the kidneys, hepatopancreas and spleen consists of fibrocytic encapsulation. Infection at the levels observed in this study were insufficient to cause lethal pathological changes, but could result in reduced food conversion ratios or impaired immunological capacity. PMID- 7797371 TI - Geographic compatibility of the freshwater snail Bulinus globosus and schistosomes from the Zimbabwe highveld. AB - Populations of Bulinus globosus were sampled from two rivers, 60 km apart, in northern Zimbabwe, and offspring from each geographic strain reared in the laboratory. Schistosomes were harvested from each strain and also maintained in the laboratory. Cross-infection experiments were conducted, whereby snails of both geographic strains were exposed to parasites of both geographic strains. Compatibility was found to be related to: (i) the geographic origin of the snail, and (ii) an interaction between the geographic origin of snail and parasite, such that sympatric combinations of snails and parasites produced a greater proportion of compatible infections than allopatric combinations. Cercarial output of infected snails was found to be related to the geographic origin of the parasite, but not of that of the snail. It is suggested that, as the snails used were laboratory bred and naive to schistosome infection, differences in snail schistosome compatibility were genetically determined, rather than an adaptive response. This study supports earlier work which suggests the existence of geographic compatibility amongst natural populations of snails and trematodes, indicative of either increased infectivity by the parasite, or decreased resistance by the snail. PMID- 7797368 TI - Physiology of two strains of Trichostrongylus colubriformis resistant and susceptible to thiabendazole and mucosal response of experimentally infected rabbits. AB - Two strains of Trichostrongylus colubriformis of ovine origin, one resistant and one susceptible to thiabendazole, were compared during experimental infection in rabbits. Groups of rabbits were infected with 5000 infective larvae (L3) of either the resistant or the susceptible strain. On days 21 and 42 post-infection (p.i.), 5 rabbits of each group were killed and the small intestine divided into three sections for worm counts and histological or biochemical analysis. Faecal egg counts were performed twice a week from day 15 to day 42 p.i. The physiology of the worms was characterised by in vitro acetylcholinesterase secretion of adult worms. The host inflammatory response was determined by peroxidase activity in mucosal homogenates and by histological counts of mast cells and eosinophils. Infectivity was not significantly different between the two strains. However, egg production was delayed and was significantly lower for the resistant strain. Conversely, in vitro secretion of resistant worms was significantly higher than the susceptible ones. The mucosal homogenetates of rabbits infected with the resistant strain had significantly higher levels of peroxidase activity in the duodenum on days 21 and 42 p.i. Mast cell counts were also significantly higher in the duodenum on day 42 p.i., in rabbits infected with the resistant strain. No difference was observed in the eosinophil counts. These results suggest that genetic variation in the nematode, such as anthelminthic resistance, is associated with variations in worm biology and physiology as well as differences in the inflammatory response of the host. PMID- 7797372 TI - Ultrastructure of the surface structures of Allodiscocotyla diacanthi (Polyopisthocotylea: Monogenea) from the gills of the marine teleost fish, Scomberoides tol. AB - Scanning and transmission electron microscopic studies have been made of the surface architecture of the fish-gill parasite, Allodiscocotyla diacanthi. Observations of the haptor region have revealed the presence of cushion-like supports at the base of each clamp, together with a pair of anchor-hooks. Other topographical features observed included a mid-ventrally positioned genital atrium and a ventrolateral vaginal pore. Tegumental serrations, composed of electron-dense bars, partially cover the hindbody, and their presence may serve in the adhesive attitude of the worm, in response to the flow of displacement water currents. The tegumental syncytium contains numerous dense granules and lucent vesicles, the contents of which are released into the cytosol of the syncytium. The clamp sclerites are invested with tegument which, in some specimens, contained inclusions resembling bacteria. Groups of neurons containing characteristic dense-cored vesicles were observed frequently in the clamp region. Each jaw of the clamp is distinguished by the presence of approximately 175 non ciliated putative sensory endings, and a pair of cone-like sensillae occurs on the ventral surface of the lappet. Additionally, the entire body surface of the worm is covered with some 3000-4000 unicilated structures that are presumed to be sensory in nature. PMID- 7797373 TI - Studies on the morphological changes in the midguts of two ixodid tick species Boophilus microplus and Rhipicephalus appendiculatus during digestion of the blood meal. AB - Light and electron microscopy were used to study the morphological changes which accompanied feeding and digestion of the blood meal in the midgut epithelium of two ixodid tick species Boophilus microplus and Rhipicephalus appendiculatus. In unfed ticks of both species, the midgut epithelium was lined by stem cells and empty digest cells in which haematin accumulated with starvation. On attachment to its hosts, differentiation of the stem cells and the loss of haematin from the midgut epithelium, seemed to be synchronous. Digestive activity with the appearance of the digest cell series started in the anterior end of the midgut when it came in contact with the blood meal. Although various stages can be distinguished, it would appear that these are in reality phases of activity of a single cell type--the digest cell. No additional evidence was obtained on other cell types. PMID- 7797374 TI - The effect of level of feed intake on the pharmacokinetic disposition of oxfendazole in sheep. AB - Oxfendazole (OFZ) containing a trace of [14C]-OFZ was administered intraruminally and intravenously to sheep fitted with rumen and abomasal cannulae and which were being fed 800 and 400 g of 50:50 lucerne:wheaten chaff daily. The [14C] was extensively associated with rumen particulate digesta, the shorter residence time of digesta in sheep on high compared to low feed intake reduced the duration of OFZ absorption. Abomasal fluid flow was greater in sheep on high than low intake and was attributed to increased gastric secretions. At high intake a greater proportion of the [14C] dose flowed from the abomasum in digesta fluid, but its residence time in the abomasum was of shorter duration compared with low intake. The more rapid passage of digesta through the gastrointestinal tract in the former sheep reduced the duration for drug desorption from particulate material and absorption into the bloodstream. In these high intake sheep and availability of [14C]-compounds in plasma was lower and more rapidly cleared than in sheep on low feed intake. Concomitant with the reduced absorption a greater proportion of the dose was excreted in faeces, and a lower proportion in the urine of sheep on high compared with low feed intake. The extensive association of OFZ and its metabolites with rumen digesta, is a principal determinant of OFZ kinetics. PMID- 7797375 TI - The effect of reduced feed intake on the efficacy of oxfendazole against benzimidazole resistant Haemonchus contortus and Trichostrongylus colubriformis in sheep. AB - Within 12 h of reducing the daily intake of a 50:50 lucerne and wheaten hay ration from 800 to 400 g, there was an increase in digesta marker concentration indicating a reduction in the flow rate of digesta fluid and particulates through the abomasum of sheep. The efficacy of the recommended dose of oxfendazole (OFZ) was then tested against benzimidazole resistant Trichostrongylus colubriformis and Haemonchus contortus in sheep whose feed intake was halved 36 h before and after drug treatment. In animals fed the reduced ration there was a 60% reduction of T. colubriformis and 94% reduction of H. contortus compared with a 19% and 60% reduction respectively on the higher feed intake. It is therefore suggested that greater anthelmintic efficacy can be achieved in sheep by temporary feed reduction. PMID- 7797376 TI - Differences in the second internal transcribed spacer (ribosomal DNA) between five species of Trichostrongylus (Nematoda: Trichostrongylidae). AB - The second internal transcribed spacer (ITS-2) of the ribosomal DNA of 5 species of Trichostrongylus has been sequenced. The ITS-2 of the 5 species was 237 or 238 bases in length, and had a GC content of approximately 30%. No evidence of intraspecific variation was detected in the ITS-2 sequence of T. colubriformis, T. vitrinus or T. retortaeformis, irrespective of the life cycle stage examined. There was evidence, however, of variation at five positions in the ITS-2 sequence of T. vitrinus samples and at one position in T. axei, indicating intra individual variation in the sequence of different copies of the ribosomal DNA. Nonetheless, there were consistent sequence differences between the five Trichostrongylus species examined. The level of interspecific differences in nucleotide sequence was low (1.3-7.6%), with the species infecting birds (T. tenuis) being genetically more different to the four species found in mammals. Some of the nucleotide differences between species occurred at the recognition sites of endonucleases, which makes them of important diagnostic value for species identification. Also of significance are the recognition sites for several enzymes located within the regions of sequence homology for the five species of Trichostrongylus. These may prove useful in distinguishing between genera of trichostrongyle nematodes. PMID- 7797377 TI - Wuchereria bancrofti filariasis in French Polynesia: age-specific patterns of microfilaremia, circulating antigen, and specific IgG and IgG4 responses according to transmission level. AB - The age-specific patterns of microfilaremia, Og4C3 antigenemia, anti-Brugia malayi IgG and IgG4 were assessed in 3 villages of low, medium and high transmission level for Wuchereria bancrofti filariasis. The prevalence rates for each of the 4 markers were clearly age dependent and their patterns strongly associated with the transmission level. The antigenemia prevalence rate was consistently higher than the microfilaremia prevalence rate, in all age groups. The prevalences of anti-B. malayi IgG and IgG4 responses were very similar and much higher than those of microfilaremia or antigenemia. Antibody responses reached the plateau at an earlier age and at a higher prevalence with increased intensity of transmission. For all the markers, the prevalence rates were significantly higher in males than in females. PMID- 7797378 TI - Immunodiagnosis of human trichinellosis and identification of specific antigen for Trichinella spiralis. AB - Crude antigens obtained from the infective stage larvae of Trichinella spiralis were used in an ELISA for detecting IgG antibodies to T. spiralis in serum samples collected from three groups of individuals. The individuals of the first group were parasitologically confirmed trichinellosis patients, while those of group 2 were patients with other helminthiasis and group 3 were healthy, parasite free individuals. The specificity of the assay was 96.8% when performed on sera of groups 2 and 3. Cross-reaction was observed with the sera of patients with capillariasis, gnathostomiasis, opisthorchiasis, and strongyloidiasis and opisthorchiasis with hookworm infection. The sensitivity of the test was 100% when performed on sera of group 1, which were collected 57 days after infection. Western blot analysis revealed that a specific antigen for T. spiralis was a component of M(r) 109. PMID- 7797379 TI - Protective immunisation of guinea pigs against Dictyocaulus viviparus using excretory/secretory products of adult parasites. AB - Parasite preparations were examined for their ability to induce protective immunity against Dictyocaulus viviparus in guinea pigs. Dunkin-Hartley strain guinea pigs were immunised with somatic extracts of adult parasites, somatic extracts of third stage larvae or excretory/secretory (ES) products from adult parasites. The groups were immunised twice with Freund's adjuvant four weeks apart and challenged with 6000 infective L3. Significant levels of protective immunity were observed only in the adult ES-immunised animals. The antibody responses of the different groups were compared following analysis by ELISA and immunoprecipitation. To examine the protective role of antibody, guinea pigs were passively immunised with serum from animals immunised with adult ES products or serum from guinea pigs exposed to experimental D. viviparus infection. Following challenge with infective L3, lung-worm burdens of these groups were significantly lower than in guinea pigs which received normal sera. The results suggest that D. viviparus adult ES products contain protective antigens and that antibody mediated mechanisms contribute to immune protection. PMID- 7797381 TI - Photochemical bleaching of fluorescent glycosylation products. AB - We have examined the effect of visible light and ultraviolet on the non-enzymatic glycosylation of lysine in vitro. Glucose and L-lysine were mixed and incubated under white light, UV-A, UV-B, or in the dark. During 15 days of incubation in the dark, a heterogeneous mixture of intensely brown chromophores developed, with a dominant fluorescence excitation maximum at 350 nm and emission maxima near 425 nm. The process was delayed or inhibited to a moderate extent by white light, whereas under UV-A and UV-B this effect was more pronounced. We conclude that non enzymatic glycosylation can be photochemically modulated by both visible light and ultraviolet. PMID- 7797382 TI - Axial and para-axial fluorophotometry in diabetic macular edema. AB - The vitreous fluorophotometric examinations were used in nonproliferative diabetic retinopathy to recognize early diabetic macular edema. Thanks to additional fixation light, axial and para-axial fluorophotometry in patients with nonproliferative diabetic retinopathy was achieved (Fluorotron Master, Coherent). The angle of deviation from the foveal scan (f) was 10 degrees in temporal (t) and nasal (n) directions. In case of non clinically significant macular edema, the posterior vitreous penetration ratio (PVPR) in the foveal scan (f) was significantly higher (p < 0.05) than in the other results (trend PVPRt < PVPRf > PVPRn). PMID- 7797380 TI - Protein glycation and in vivo distribution of human lens fluorescence. AB - Glycated proteins formed by the Maillard reaction were measured by furosine determination in human normal lenses and in senile and diabetic cataracts. Furosine, an hydrolysis product of fructose-lysine adduct formed in the early stages of the Maillard reaction, was measured by high performance liquid chromatography (HPLC). Furosine levels in diabetic cataracts were found to be 3 to 4 times higher than those observed for senile cataracts. The increased glycation levels both in cortex and nucleus were related to the increase of fluorescence determined in vitro by fluorometry and in vivo by Scheimpflug photography. Lens proteins were incubated with glucose and it has been demonstrated that protein glycation occurred parallel with the increase in concentration of fluorescent chromophores that present similar characteristics as those observed in vivo. The results indicate that protein insolubilization seemed to involve preferentially glycated proteins and at least in diabetic cataracts, the process seems to be initiated in the cortical region. PMID- 7797384 TI - Corneal autofluorescence in diabetic and normal eyes. AB - Corneal autofluorescence has been lately studied as a predictor of retinopathy severity in diabetic patients. We measured corneal autofluorescence in 138 eyes of 69 diabetic patients and 64 eyes of 32 healthy controls. Diabetic patients were subdivided by the severity of retinopathy according to the Modified Airlie House Classification (stage 1: no or minimal retinopathy; stage 2: minimal background retinopathy; stage 3: background retinopathy; stage 4: (pre-) proliferative retinopathy. The fluorescence peak value and the area underlying the corneal autofluorescence curve were measured with a scanning fluorophotometer (Fluorotron Master, Coherent Radiation Palo Alto CA) Healthy controls' values of corneal autofluorescence (peak value: mean 11.03 +/- 3.77 ng. equivalent fluorescein/ml; area: mean 163.85 +/- 61.40 scan-point x ng. equivalent fluorescein/ml) resulted similar (peak value: p = 0.83; area: p = 0.61) to those of diabetic patients without retinopathy (peak value: mean 11.2 +/- 3.4 ng.eq/ml; area: 170.07 +/- 57.23 scan-pnt.ng.eq/ml). A statistically significant difference was found between diabetic patients without retinopathy and patients with stage 2, 3, 4 retinopathy. No statistically significant difference was found both for the peak value (p = 0.50) and for the area (p = 0.61) between stage 3 and stage 4 retinopathy. The sensitivity and specificity of corneal autofluorescence as a screening test for diabetic retinopathy were 82% and 62% for the peak value, 87% and 60% for the area; the positive predictive value for the presence of diabetic retinopathy was 65% for the peak and 63% for the area. PMID- 7797383 TI - The relation between corneal autofluorescence, endothelial cell count and severity of the diabetic retinopathy. AB - We measured the corneal autofluorescence in groups with different levels of diabetic retinopathy severity (72 eyes of 46 patients) and in age-matched non diabetic controls (34 eyes of 24 controls). We also estimated the corneal endothelium cell count and pachymetry with a contact specular microscope. For the controls, mean corneal autofluorescence was 8.8 ng equivalents fluorescein/ml (SD 0.3). Results showed increased autofluorescence of the cornea in diabetic patients (mean 17.9 ng equivalents fluorescein/ml, SD 4.2), related to the duration of diabetes (P < 0.05) and to the severity of diabetic retinopathy (P < 0.0001). Corneal endothelial cell count results showed no statistically significant relation to corneal autofluorescence (P < 0.6), indicating that the increased autofluorescence cannot be attributed to a change in corneal cell density. PMID- 7797386 TI - Aqueous penetration of orally administered ciprofloxacin in humans. AB - The aqueous penetration of orally administered Ciprofloxacin (CPX) was studied in twenty-two human volunteers undergoing cataract surgery. CPX in a dose of 250 mg, was given p.o. at 12 hourly intervals in 3 groups such that a maximum dose of 0.5 grams was delivered in one group, 1.0 grams in another and 1.5 grams in the last group. A fourth group consisted of 6 individuals who were controls and received lactose tablets. Twelve hours after the last dosing aqueous samples were collected and assayed by the Grove-Randall technique. The aqueous penetration of Ciprofloxacin achieved was 1.51 +/- 0.15 mgL-1 in group II and 2.49 +/- 0.52 mgL 1 in group III. In group I, the aqueous concentration was experimentally indeterminate and the control samples in group IV did not show any antibacterial activity. Divided oral doses of 1.5 grams of CPX were found to produce an aqueous titre up to 2.5 times the MIC of Ps. aeruginosa. PMID- 7797385 TI - Ivermectin dosing based on physical appearance. AB - Ivermectin is a safe and effective microfilaricide which has been shown to have a beneficial impact on some onchocercal eye lesions. Current requirements for the distribution of ivermectin are that patients be weighed, and that their dose be determined according to their weight. This requirement increases the cost of distributing the drug to communities in need of treatment and, when scales breakdown, may lead to the suspension of distribution. Data are presented on a simple, alternative method of dose assessment based on the physical appearance of the patient. Fifteen assessors achieved an overall level of agreement with the weight-based schedule of 86% on a sample of 6420 patients. The level of agreement varied between assessors, from 73% to 95%. About 6% of the population would have received doses outside the range of the current weight-based schedule. We believe that the current insistence that each individual's dose of ivermectin be determined by weighing will hamper efforts to distribute the drug to those most in need of it and that our data indicate that workers can be trained to distribute ivermectin safely without weighing every individual. We would welcome confirmation of our findings from other populations. PMID- 7797387 TI - Frequency and complications of chronic iridocyclitis in ANA-positive pauciarticular juvenile chronic arthritis. AB - Chronic iridocyclitis (CI) is among the most important extra-articular manifestations of juvenile chronic arthritis (JCA) and is most often observed in young girls with pauciarticular JCA and circulating antinuclear antibodies (ANAs). The frequency of CI found in 39 children with ANA-positive pauciarticular JCA was 56%. None of the patients developed ocular complications during follow up. We think that this favourable outcome was primarily due to the early diagnosis and to our choice of using atropine as a mydriatic agent and to prolong atropine, after having spaced its administration further apart, up to one year or longer after the remission of ocular manifestations. PMID- 7797388 TI - Immunopathological findings in posterior scleritis. AB - Posterior scleritis can present with a variety of symptoms, and its clinical diagnosis is therefore difficult. Little is known about the pathogenesis and the cellular effector mechanisms. This case report presents the immunopathological findings of posterior scleritis in the enucleated eye of a 28-year-old female with no known underlying disease. The cells infiltrating the scleral fibers consisted predominantly of T cells. Many of them were CD4 cells. Clusters of T and B cells were found in perivascular areas. No signs of primary vasculitis were seen. The cellular infiltrate in posterior scleritis shows features compatible with a T-cell-mediated (autoimmune) disorder. PMID- 7797389 TI - Blood-aqueous barrier permeability determination in HLA B27-positive acute anterior uveitis patients. AB - The blood-aqueous barrier (BAB) permeability was studied by fluorophotometry in 17 healthy control subjects and in 27 eyes from 27 patients with HLA-B27-positive acute anterior uveitis (HLA-B27 AAU). Twenty of these patients had an associated spondyloarthropathy. BAB permeability was studied during the ocular inflammatory crisis and in the disease-free periods in the same patients. Anterior chamber fluorophotometric scans were performed before and 30 minutes after the intravenous injection of 14 mg/kg of sodium fluorescein. The diffusion coefficient (Kd) was obtained from the ratio between the fluorescein concentration in the anterior chamber and the NPBF. Data were analyzed using the Student's t test and analysis of variance. A statistically significant difference (P < 0.001) was found between the Kd of active HLA-B27 AAU (61.4 +/- 16.8 x 10( 4) min-1) and the Kd of inactive HLA-B27 AAU (4.8 +/- 1.6 x 10(-4) min-1). No statistically significant differences were found between the Kd of inactive HLA B27 AAU and the Kd of the control subjects (4.3 +/- 1.0 x 10(-4) min-1). We also failed to detect significant differences between patients with and without spondyloarthropathy either during the acute attack or during the disease-free period. On the basis of these results we conclude that the permeability of the BAB remains intact in inactive HLA-B27-positive AAU. The parallel fluorophotometric behaviour of HLA-B27-positive AAU with spondyloarthropathy and without spondyloarthropathy suggests that both share a common pathogenetic mechanism. PMID- 7797390 TI - Fluid air exchange in vitreo retinal surgery. AB - This study evaluates the efficiency of fluid-air exchange on the reattachment of the retina and clarifies the possibility that a posterior retinotomy is a cause for intra- and postoperative complications. A consecutive series of 211 eyes with retinal detachments due to P.V.R. (47%), diabetic traction, perforating trauma, macular hole or giant tears is presented. All eyes underwent pars plana vitrectomy, fluid-air exchange, internal drainage of subretinal fluid, laser endophotocoagulation and scleral buckling of the tears; 56% of the eyes were phakic and 55% underwent a posterior retinotomy, 54% underwent tamponade with C3F8 and 46% with silicone oil. Intraoperatively the retina was completely flattened in 91% cases. The causes of incomplete reattachment were residual membranes (6.6%), poor visualization (1.4%) and suprachoroidal hemorrhage (1%). These complications were isolated as being the cause of the bad final results (p < 0.001). Postoperatively, the retina remained attached in 66% of cases after the first procedure and with further surgery in 81% (mean follow up 16 months). Best corrected visual acuity was improved in 73% of eyes, unchanged in 17%, and worse in 10%. Complications were retraction of the retinotomy site in 3 cases and peripheral choroidal hemorrhage in 4 cases. We concluded that fluid air exchange with internal subretinal fluid drainage was an efficient and safe technique even if a posterior retinotomy was necessary. PMID- 7797392 TI - [Classification of health benefits of the national health system]. PMID- 7797394 TI - [Definition of health benefits covered by the national health system]. PMID- 7797393 TI - [Classification of benefits: health aspects]. PMID- 7797391 TI - Decreased corneal complications after no-reflux, low-dose 5 fluorouracil subconjunctival injection following trabeculectomy. AB - In order to reduce corneal complications in 27 glaucomatous eyes that underwent trabeculectomy and postoperative subconjunctival injection of 5-fluorouracil we tried 1) a low-dose administration of 5-fluorouracil and 2) a modified subconjunctival injection technique. The mean total 5-fluorouracil dose was 18.0 +/- 6 mg. A life-table analysis showed a success rate, at 15 months, of 78% (+/- 7 S.E.). Four of the 27 eyes (13%) had corneal complications, limited to punctate keratopathy, with no corneal epithelial defects and/or abrasions. Our study shows that corneal complications decreased when the contact between 5-fluorouracil and the ocular surface was reduced. PMID- 7797396 TI - [Health benefits in preventive medicine and public health]. PMID- 7797395 TI - [Health benefits of the national health system: legal aspects]. PMID- 7797397 TI - [Benefits of the national health system: rationalization criteria]. PMID- 7797398 TI - [Analysis of the draft of classification and cataloguing of health benefits in the national health system: primary care]. PMID- 7797399 TI - [Oro-dental health: brief note regarding the Draft of the Royal Decree on the prescription of health benefits of the national health system]. PMID- 7797400 TI - [Text of the royal decree on the classification of health benefits of the national health system]. PMID- 7797402 TI - Proinflammatory effects of morphine in the rat adjuvant arthritis model. AB - Morphine has been shown to alter various aspects of the immune response. We examined its effect on progression of the T-cell-mediated model, rat adjuvant arthritis. Saline, morphine or the opioid antagonist naloxone were administered to male Wistar rats via subcutaneous osmotic pumps implanted three days prior to adjuvant disease induction by an intra-dermal injection of Mycobacterium tuberculosis in oil. The time of disease onset was found to be accelerated (day 11) for the morphine group as compared to the saline control (day 13). In addition morphine produced a significant increase in paw swelling (days 13 and 14), bone demineralization and bone erosions. A significant decrease in body weight as compared to the saline control was also observed. Naloxone had no significant effect on the degree of the inflammation seen, although like morphine it significantly increased bone demineralization and bone erosions as assessed by radiography. PMID- 7797401 TI - Effects of cytogenin, a novel anti-arthritic agent, on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats. AB - The anti-arthritic effects of cytogenin (8-hydroxy-3-hydroxymethyl-6- methoxyisocoumarin) on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats were examined. Prophylactic treatment with cytogenin (30, 100 mg/kg) had a potent inhibitory effect on type II collagen induced arthritis. Prophylactic or therapeutic treatment with cytogenin (10, 30 and 100 mg/kg) also had a potent inhibitory effect on adjuvant arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), cytogenin (10, 30 and 100 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw oedema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of the anti-arthritic action of cytogenin is different from that of NSAIDs and that cytogenin may become a useful drug for the treatment of rheumatoid arthritis. PMID- 7797403 TI - Modulation of proteoglycan composition in cultured anatomically intact joint cartilage by cyclic loads of various magnitudes. AB - The anatomically intact articular cartilage (area approximately 2.5 cm2) of 6 month-old bovine sesamoid bones was cyclically (0.3 Hz) loaded with 0, 5, 25 and 50 kg in vitro for 7 days. The amount and composition of the proteoglycans that were synthesized during the last 17 hours of incubation under each regime were studied. Loads of all magnitudes produced a 45% overall increase in synthesis, which included a disproportionate increase in the synthesis of small proteoglycans. Loading with either 25 or 50 kg induced the synthesis of much larger glycosaminoglycan side-chains and a species of small proteoglycan rich in keratan sulfate. Under these greater loads, synthesis in the deep layer of the cartilage was reduced and there was focal damage to the cartilage surface. PMID- 7797404 TI - Further studies on satellite nucleoli of lymphocytes in patients suffering from B chronic lymphocytic leukaemia. AB - Satellite nucleoli were studied in lymphocytes of patients suffering from various stages of B chronic lymphocytic leukaemia without and after treatment with cytostatic monotherapy with chlorambucil. The percentage of lymphocytes with satellite nucleoli in the peripheral blood of investigated patients was very constant and showed only a statistically non-significant slight trend to decrease in the most advanced stage of the disease. In contrast, the count of these cells increased in advanced stages of the disease, and decreased after the cytostatic chemotherapy. From the methodological point of view, satellite nucleoli may be easily visualized by means of a simple staining for RNA with acidified basic dyes without fixation. Such staining provided similar results as cytochemical immunoreactions for the characteristic nucleolar protein B23. PMID- 7797405 TI - Effect of L-propionyl carnitine on in-vitro membrane alteration of sickle-cell anaemia erythrocytes. AB - Sickle-cell anaemia erythrocytes are under oxidative stress which contributes to some of the reversible and irreversible modifications observed in these cells. L Propionyl carnitine, which protects myocardium, endothelium and erythrocytes from peroxidative damages and is able to stabilize damaged cell membranes, is also able to decrease the formation of thiobarbituric acid reactive substances which are produced by incubating erythrocytes with hydrogen peroxide in the presence of atmospheric oxygen or 95% N2-5% CO2 mixture. In these experimental conditions the increase of thiobarbituric-acid-reactive substances is significantly lower at 5 mM and 10 mM L-propionyl-carnitine concentrations. The formation of irreversibly sickled cells induced by 24-h incubation of sickle-cell anaemia erythrocytes under 95% N2-5% CO2 mixture is significantly decreased in the presence of 1 mM or higher L-propionyl-carnitine concentrations. The percent filtration of sickle red blood cells through micropore filters is significantly decreased at oxygen tensions between 20 and 40 mmHg. These in-vitro observations suggest that L propionyl carnitine may be beneficial in maintaining the normal shape of sickle cell anaemia erythrocytes at low oxygen tension and in decreasing the peroxidative damages which accumulate during the life of red blood cells. PMID- 7797406 TI - Identifying nurses vulnerable to role conflict. AB - To remedy the nursing shortage in the US, hospitals initially focused on expensive recruitment efforts to fill nursing vacancies. Few addressed a core component of the problem: role conflict, which when reduced can be instrumental in hospitals attracting and retaining nurses. PMID- 7797408 TI - The role and use of support personnel. AB - In 1991 a research team from the University of Alberta was given the go-ahead by the National Health Research and Development Program, Health and Welfare Canada to investigate the role and use of support personnel in the rehabilitation disciplines and to provide a preliminary database in nursing. Below, the study findings on the future use, supervision and training of support personnel. PMID- 7797409 TI - When to begin a doctoral programme in nursing. AB - The future of the nursing profession is strengthened by the expansion of nursing science and its integration with nursing practice, the hallmarks of doctoral education. Launching a doctoral programme in nursing is a monumental venture into the main stream of higher education; consequently, the readiness to begin such an effort must be carefully assessed. PMID- 7797410 TI - Magnetization transfer and high-dose contrast in early brain infection on magnetic resonance. AB - RATIONALE AND OBJECTIVES: The authors studied the effect of contrast dose, use of magnetization transfer (MT), and temporal delay on the visualization of contrast enhancement with gadoteridol (Gd HP-DO3A) in a canine brain abscess model. METHODS: Alpha streptococcus brain abscesses were studied in five dogs at 1.5 tesla (T) 1 and 5 days after implantation. Scans were performed 1, 11, and 21 minutes after contrast was administered, using an initial dose of 0.1 mmol/kg. A supplemental contrast injection of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg), with scans repeated at 31, 41, and 51 minutes. RESULTS: Lesion conspicuity on day 1 was greater at high-contrast doses (0.3 mmol/kg) compared with standard doses (0.1 mmol/kg), regardless of whether imaging was performed without (0.89 +/- 0.02 compared with 0.26 +/- 0.08) or with (0.97 +/- 0.04 compared with 0.28 +/- 0.06) MT. High-dose, MT, and a delay after contrast was injected all produced a statistically significant improvement. On blinded review of films obtained 11 and 14 minutes after injection, enhancement of the lesion could not be identified with certainty in two of five dogs at a dose of 0.1 mmol/kg, regardless of whether MT was used. Enhancement was seen consistently in all lesions at 0.3 mmol/kg. On day 5, results were comparable, with greater absolute enhancement. CONCLUSIONS: In early brain infection, high-contrast doses (0.3 mmol/kg), MT, and a moderate delay after injection all improve visualization of lesion enhancement. PMID- 7797407 TI - Planning nursing resources. AB - In the UK the health service is undergoing radical changes to become more responsive to local needs, consumer feedback and modern medical technology. To keep up with this constantly changing health care environment, nurse resource planning must be flexible and responsive. Below, an outline of some of the information, tools and skills required to formulate nursing resource plans. PMID- 7797412 TI - Application of the maximum entropy method for evaluating phosphorus-31-magnetic resonance spectra in patients with liver metastases. AB - RATIONALE AND OBJECTIVES: The clinical feasibility and application of the maximum entropy method for data analysis from in vivo phosphorus-31-magnetic resonance (P 31-MR) spectra of the liver were determined. METHODS: Image-guided localized P-31 MR spectroscopy was performed in 24 patients with liver metastases and in 20 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T using a surface coil. Phosphomonoester/beta-adenosine triphosphate (ATP), phosphodiester/beta-ATP, and inorganic phosphate/beta-ATP were calculated from the maximum entropy method-spectra and from spectra evaluated with standard data processing (Fourier transformation spectra). RESULTS: Phosphomonoester/beta ATP and phosphodiester/beta-ATP were increased significantly with both methods in patients' spectra. Maximum entropy method spectra showed a distinct pattern with low noise. It was easier to determine peak borders and to attach resonances to the different metabolites using this method. CONCLUSIONS: Maximum entropy method is an alternative method for evaluation and quantification of P-31-MR spectra data and is preferred to standard data processing with Fourier transformation in cases of reduced signal-to-noise ratio of spectra. PMID- 7797411 TI - Effects of iopromide on vasoactive peptides and allergy-mediated substances in healthy volunteers. AB - RATIONALE AND OBJECTIVES: Little information is available about the direct action of angiographic contrast media on vasoactive peptides and allergy-mediated substances in humans. This study defined the acute effects of iopromide, a nonionic contrast medium (370 mg/mL iodine), on vasoactive peptides, allergy mediated substances, and hemodynamic parameters in healthy volunteers. METHODS: Pulmonary digital subtraction angiography was performed in seven healthy volunteers with no cardiovascular or pulmonary disease. Iopromide was administered as a total volume of 100 mL through a 7-Fr catheter inserted in the right femoral vein. The injected volumes and duration of injection (15-20 mL/second) were kept constant. The following hemodynamic parameters were monitored continuously: results of electrocardiogram, heart rate, and phasic and mean pulmonary arterial and peripheral arterial pressures. Blood samples were obtained before and 3 to 5 minutes after injection of contrast media to determine the concentrations of the following vasoactive peptides: renin, angiotensin I converting enzyme, angiotensin II, aldosterone, atrial natriuretic peptide, antidiuretic hormone, cyclic guanosine monophosphate, and myoglobin; and to allergy-mediated substances such as tryptase, eosinophil protein X, and eosinophil cationic protein, using radioimmunoassay techniques. RESULTS: Iopromide substantially increased atrial natriuretic peptide (48.8 +/- 8.9 to 85.8 +/- 13.0) and antidiuretic hormone (3.4 +/- 0.3 to 4.6 +/- 0.5) levels, whereas renin decreased (0.9 +/- 0.1 to 0.8 +/- 0.2) slightly but not significantly. Iopromide did not induce substantial changes in the other vasoactive peptides or in allergy-mediated substances after the contrast medium was injected. Similarly, cardiovascular parameters (heart rate, pulmonary and systemic blood pressures, and results of electrocardiogram) also remained unchanged after contrast injection. CONCLUSION: Iopromide caused no appreciable hemodynamic alterations associated with the changes in atrial natriuretic peptide and antidiuretic hormone and no evidence of allergy-mediated reactions in all volunteers. PMID- 7797413 TI - Transplacental passage and milk excretion of iobitridol. AB - RATIONALE AND OBJECTIVES: Iobitridol, a new nonionic, low-osmolality urographic and angiographic contrast medium, is a marker of extracellular fluid. Excretion of iobitridol in goat's milk and transplacental passage in the gestating rabbit were evaluated compared with iohexol. METHODS: Both products were determined in biologic samples by two analytic methods: ultraviolet spectrometry (milk) and high-pressure liquid chromatography (maternal and fetal blood and amniotic fluid). RESULTS: Excretion in the milk represents 0.7% of the administered dose for iobitridol and 1.6% for iohexol. Transplacental passage is nonexistent. Iobitridol and iohexol behave in a similar manner. CONCLUSIONS: These preclinical results allow more effective prediction of the safety of iobitridol in pregnant or lactating women. However, precautions for use must be respected in the absence of specific studies in this population group. PMID- 7797414 TI - Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate--, and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart. AB - RATIONALE AND OBJECTIVES: Manganese dipyridoxyl diphosphate (MnDPDP) is a promising contrast agent for magnetic resonance imaging of the liver. The authors explored the possibility that high concentrations of MnDPDP may cause manganese ion (Mn++)-induced side effects on cardiac function. METHODS: Potential cardiodepression by MnDPDP, DPDP--, and manganese chloride (MnCl2) (100-3,000 mumol/L) was investigated in the isolated rat heart, with left ventricular developed (systolic--end-diastolic) pressure and heart rate as the primary indices of cardiac function. RESULTS: During 5-minute exposures, 10% and 50% decreases in left ventricular developed pressure were observed for MnDPDP, 250 mumol/L and 1580 mumol/L; DPDP--, less than 100 mumol/L and 1000 mumol/L; MnCl2, 30 mumol/L and 250 mumol/L. Heart rate changes were not observed with MnDPDP. Cardiodepression was reversed within 2 minutes during a 14-minute recovery period for all investigated concentrations of MnDPDP and was less rapid for the highest concentrations of MnCl2. CONCLUSIONS: Manganese dipyridoxyl diphosphate is well tolerated in the rat heart at concentrations as high as 200 to 250 mumol/L and is approximately 10 times less cardiotoxic than MnCl2. Cardiodepressive effects of MnDPDP in the present rat heart model, perfused in the absence of blood and proteins, are related primarily to the release of free Mn++ ions and in part to the simultaneous release of DPDP--. PMID- 7797415 TI - Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine levels. AB - RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the temporal relation between the change in the resistive index (RI) from renal Doppler sonography and that of serum creatinine values in the course of experimentally induced reversible acute renal failure (ARF) in rabbits. METHODS: Reversible ARF was induced in 10 New Zealand white rabbits by injecting a glycerol solution (6.0 mL/kg) into the thigh muscle. Doppler sonography was performed before injection, and 6, 12, and 24 hours, and 3, 5, 7, and 14 days after injection of glycerol. Blood samples for measuring serum creatinine levels were obtained in the same time sequence. Three rabbits, which died during the course of the experiment, were excluded from the study group. RESULTS: The RI elevated rapidly after glycerol injection, peaked at 12 hours, and then decreased to normal values by 7 days. Conversely, serum creatinine values were elevated and peaked at 1 day and then decreased to normal by 14 days. The change in the RI preceded the change in serum creatinine levels in the course of reversible ARF. There was a weak linear correlation between RI and serum creatinine levels, with a correlation coefficient of 0.33. CONCLUSION: Doppler sonography with measurement of resistive index may be useful in predicting the course of ARF. PMID- 7797417 TI - Reliability of three methods of radiologic assessment in patients with rheumatoid arthritis. AB - RATIONALE AND OBJECTIVES: To assess the intraobserver reliability of three methods used frequently to evaluate joint destruction in rheumatoid arthritis: the Sharp method, the Larsen method, and the carpo:metacarpal ratio. METHODS: One observer analyzed twice within a 6-week interval 71 radiographs from patients with rheumatoid arthritis. Reliability was estimated by intraclass correlation coefficient (R) and by Altman-Bland graphical method. Correlations were examined by the Spearman's coefficient (r). RESULTS: The intraobserver reliability of each method appeared satisfactory with a good result for the Sharp method (R = 0.97). The correlation was strong (r > 0.80) between the results obtained by Sharp's and Larsen's methods and weaker between the results of the two former methods and the carpo: metacarpal ratio. CONCLUSIONS: Sharp's method should be used preferentially in studies evaluating the radiologic changes in rheumatoid arthritis over time, especially in clinical trials. The carpo:metacarpal ratio may be considered as a complementary method, when wrist destruction is of conceptual importance. PMID- 7797416 TI - Contractile responses to electrolyte changes during coronary bolus perfusion. A comparative study in isolated rat, guinea pig, and rabbit hearts. AB - RATIONALE AND OBJECTIVES: The authors studied cardiac contractile responses during coronary bolus perfusion, as in coronary angiography, in three species and related the responses to the bolus content of electrolytes and to patterns of cardiac electrolyte regulation. METHODS: Isolated, paced hearts from the rat, guinea pig, and rabbit were subjected to coronary perfusion in the global mode with recording of left ventricular developed pressure during exposure (< 7.5 seconds) and recovery (30 seconds). RESULTS: In series 1 of the experiments, the perfusate reduction to one fifth of normal Ca, Na, K, Mg, and Ca/Na/K/Mg, and the removal of all ions, led to the following percentage changes in left ventricular developed pressure: rat -64, +84, -38, +7, +40, and +79; guinea pig -43, +48, +18, +5, +28, and +37; and rabbit -32, +60, +14, +4, +22, and +33. CONCLUSIONS: Except for K reduction, inducing negative inotropy in the rat but positive inotropy in the guinea pig and the rabbit, the three species responded similarly. Thus, changes in left ventricular developed pressure were related to changes in direction and rate of the sarcomal Na-Ca exchange. In series 2 of the experiments, iohexol (150 mg I/mL) +/- minor electrolyte additives were studied. Additives with Na 30 mmol/L only or with Na, Ca, K, and Mg carefully balanced reduced positive and negative inotropic responses in all three species. PMID- 7797418 TI - Conventional film-screen versus computed storage phosphor radiography. Simulated miliary lung disease in an anthropomorphic phantom. AB - RATIONALE AND OBJECTIVES: In this experimental study, the authors examined whether laser printed hardcopies from digital storage phosphor radiographs yield diagnostic performance equal to conventional film-screen radiographs in the detection of simulated miliary disease, using a standardized object. METHODS: A commercially available anthropomorphic chest phantom was used for radiographic evaluation. Miliary disease was simulated by superimposing one to four sheets of millet seeds on the lungs, resembling a miliary disease pattern with varying degrees of detectability. An observer study (receiver-operating characteristic) with eight radiologists was conducted to compare the reader performance using hardcopies of computed storage phosphor radiography versus the conventional film screen system, optimized for chest x-rays. The digitally generated images were presented as a double-image hardcopy, with a conventionally adopted version and an edge enhanced image version. RESULTS: When analyzed separately, one out of the eight observers performed slightly better using the conventional films. When treated as a group, analysis of the areas under the receiver-operating characteristic curves demonstrated no significant difference in reader performance for each of the systems under investigation (t = 0.286). The Wilcoxon test could not prove a statistical difference. CONCLUSION: Storage phosphor technology is a method that yields equal diagnostic performance as conventional film in evaluating miliary disease of the chest. PMID- 7797419 TI - Effects of carbon dioxide arterial infusion on hepatic biochemistry and histology in a rabbit model. AB - RATIONALE AND OBJECTIVES: The objective of this study was to determine the effect of carbon dioxide (CO2) infusion on hepatic biochemistry and histology in a rabbit model. METHODS: The study population consisted of 24 anesthetized rabbits that received hepatic infusion of either CO2 or saline (control) at doses of 10 mL/kg, comparable with those doses used in human clinical trials. Blood for clinical chemistry analysis was collected at baseline, 1 hour, 24 hours, and 168 hours (7 days) postprocedure. The rabbits were killed at 7 days postprocedure and the liver examined histologically for hepatic damage. RESULTS: There were no significant differences between the CO2 and the control groups in dorsal, ventral, and dorsal/ventral scores. Increases in alanine, an important indicator of hepatocellular membrane injury, in the CO2 group were significantly greater at 1 hour and 24 hours posttreatment (P = 0.037 and 0.013). However, the mean levels at 168 hours (7 days) were not significantly different (P = 0.22). The increases at 1 and 24 hours were small, transient, and considered clinically insignificant. CONCLUSION: No long-term hepatic effects in these animals were suggested by biochemical and histological examinations. PMID- 7797420 TI - Effects of simvastatin on liver and plasma levels of cholesterol, dolichol and ubiquinol in hypercholesterolemic rats. AB - Increased levels of blood cholesterol are considered as a major factor in the development of atherosclerosis. Simvastatin, a drug which blocks hydroxymethylglutaryl coenzyme A reductase (HMGCoAR), reduces plasma cholesterol and increases HDL-cholesterol in rats fed a hypercholesterolemic diet. Moreover, simvastatin produces a significant decrease of ubiquinol and dolichol in plasma and in liver. PMID- 7797421 TI - Symposium on Polyamines: Biological and Clinical Aspects. Trento, June 8-11, 1994. Abstracts. PMID- 7797422 TI - Follicular dendritic cells and apoptosis: life and death in the germinal centre. AB - The germinal centre forms a specialized microenvironment thought to play a key role in the induction of antibody synthesis, affinity maturation of B cells and memory B cell formation. Clonal-expanded follicular B lymphocytes with mutated antigen receptors (centrocytes) have to be selected on the basis of their capacity to compete for binding to antigen held in limited amounts on the follicular dendritic cells. In this way, only high-affinity B cells are selected. Binding to a follicular dendritic cell is an unconditional prerequisite for centrocytes to survive. Cells that do not succeed in binding to a follicular dendritic cell die rapidly by apoptosis. Apoptosis is a common form of cell death characterized by the activation of an endonuclease culminating in nuclear destruction. The pathway by which apoptosis is triggered varies from cell type to cell type. However, for germinal centre B cells this process is still poorly understood. PMID- 7797423 TI - Immunogold labelling indicates high catalase concentrations in amorphous and crystalline inclusions of sunflower (Helianthus annuus L.) peroxisomes. AB - Immunogold labelling and electron microscopy were used to investigate whether catalase was present in peroxisomal inclusions, the composition of which has not yet been determined in plant cells. In the mesophyll cells of sunflower (Helianthus annuus L.) cotyledons, the catalase gold label was confined to peroxisomes. At day 2 of postgerminative growth in darkness, peroxisomes were free of inclusions, and the matrix was homogeneously labelled with gold particles. Thereafter, amorphous inclusions appeared, but by day 5 of growth, conspicuous crystalline inclusions (cores) were the predominant type. This developmental change, first observed in cotyledons grown in continuous light between day 2.5 and 5, also took place in cotyledons kept in permanent darkness. Both amorphous and crystalline inclusions showed a much higher immunogold label than did the peroxisomal matrix, indicating that catalase was a component of both types of peroxisomal inclusions. In contrast to catalase, the immunogold label of glycolate oxidase was almost completely absent from cores and was confined to the peroxisomal matrix. Together with reports on the absence of other enzymes from peroxisomal inclusions in sunflower and other species (Vaughn, 1989) our results suggest that catalase is a major constituent of amorphous and crystalline peroxisomal inclusions in plants. PMID- 7797425 TI - Glycans of the early human yolk sac. AB - The pattern of glycan distribution in the early human yolk sac has been investigated using a panel of lectins. Two 6-week and one 8-week human yolk sacs, and one 8-week fetal liver from live, ectopic pregnancies were fixed and embedded in epoxy resin. Lectin histochemistry was carried out on sections of these tissues using 23 biotinylated lectins and an avidin-biotin peroxidase revealing system. Mesothelial surfaces expressed most subsets of N-glycans (other than high mannose types), N-acetyl-lactosamine, sialic acid, and alpha 1,6-N acetylgalactosamine. Endodermal surface and lateral membranes resembled those of mesothelium, but showed a preponderance of alpha 2,6-sialyl residues. Most intracellular granules contained N-glycan. There was a marked heterogeneity of granules in the endodermal cells, with different subsets varying in both staining and positional characteristics. The mesenchymal matrix bound most of the lectins used in the study, and expressed fucosyl residues which were also detected in the endothelium. Fetal liver parenchyma showed very similar staining patterns to those seen in the endoderm except for the distribution of N-acetylglucosamine, which was sparse. Despite some common features, each germ cell layer had a distinct 'glycotype', with some saccharides showing extreme topographical restriction. PMID- 7797424 TI - Cell proliferation in prostatic carcinoma: comparative analysis of Ki-67, MIB-1 and PCNA. AB - Antibodies to assess the proliferative index of tumours are being increasingly employed together with established markers for prognostic evaluation. This study set out to compare three cell proliferation markers, Ki-67, MIB-1 and PCNA, utilizing a semi-quantitative method of assessment, in 20 human prostatic carcinomas. The streptavidin-biotin immunostaining system was used for the monoclonal antibodies MIB-1 and PCNA and an indirect immunoperoxidase assay for the monoclonal antibody Ki-67. Significant correlations were found between the expression of Ki-67 in frozen tissues and MIB-1 in formal saline-fixed wax embedded tissues (p = 0.0003); between Ki-67 and PCNA expression in Bouin's-fixed tissues (p < or = 0.0001); and MIB-1 (formalin-saline-fixed tissues) and PCNA (Bouin's-fixed tissues) (p < or = 0.0001). A more intense nuclear staining pattern with less heterogeneity was observed for MIB-1 compared with PCNA, suggesting the antibody of choice, on formal saline-fixed tissues, is MIB-1, which closely correlated with Ki-67, a marker we have previously shown to be of prognostic value in prostatic carcinoma. PMID- 7797426 TI - A comparison of membrane enzymes of human and pig oesophagus; the pig oesophagus is a good model for studies of the gullet in man. AB - The distribution and relative catalytic activities of five plasma membrane enzymes (alkaline phosphatase, dipeptidyl peptidase IV, gamma-glutamyl transpeptidase, microsomal alanyl aminopeptidase and glutamyl aminopeptidase) were examined in human and pig oesophagus. In both species, alkaline phosphatase activity occurred in basal and suprabasal cells of the epithelium and in capillaries. Stromal cells in the human submucosa were particularly reactive. Dipeptidyl peptidase IV was present in blood vessels and capillaries in man and pig and in submucous glands in the pig. The enzyme was also present in both species in the lamina propria cells immediately adjacent to the epithelial basal lamina. In the human, gamma-glutamyl transpeptidase occurred in the epithelial basal cells and in isolated basal and lower prickle cells in the pig. Stromal cells in the human submucosa were strongly reactive and capillaries in the muscularis propria in both species moderately active. Microsomal alanyl aminopeptidase was detected in lamina propria cells adjacent to the epithelial basal cell layer in man and pig and at the apices of mucous cells in pig submucous glands. Weak glutamyl aminopeptidase activity was confined to capillaries in both species. The findings of this study, along with the ready availability of pig oesophagus, suggest that the pig may be a suitable model for studies of the gullet in man. PMID- 7797427 TI - Postembedding alpha-tubulin immunolabelling of isolated centrosomes. AB - Accurate ultrastructural localization of the components of centrosomes is an important step toward the determination of their function. We have used an electron microscopy procedure to preserve centrosome-associated antigens which enables their high-resolution localization. The unique part of our procedure is the application of a post-sectioning fixation step which overcomes the poor section contrast and morphological appearance that limits the use of low temperature processing and Lowicryl embedding. The efficacy of our approach is demonstrated by the efficient labelling of alpha-tubulin in the well-preserved and contrasted microtubule barrels of the centrides of isolated mammalian centrosomes. PMID- 7797429 TI - Women's healthcare comes to the forefront in the 1990s: are physicians ready? PMID- 7797428 TI - Detection of a glycosphingolipid antigen in bladder cancer cells with monoclonal antibody MRG-1. AB - The monoclonal antibody MRG-1 has been evaluated for the immunohistochemical detection of the type 3 chain of blood group A in human normal bladder epithelium and bladder tumours. Light microscope examination of paraffin sections demonstrated that this antigen was present in normal epithelium and superficial bladder tumour in patients with blood group A or AB, but was absent in the invasive type of bladder tumour. In normal epithelium, the plasma membrane was positive for this antigen, and the cytoplasm was diffusely stained. In superficial transitional cell carcinoma, the plasma membrane was negative, whereas the cytoplasm was intensely stained in the perinuclear region. This pattern was different from that observed for type 1 and 2 group A antigen, which was recognized mainly at the plasma membrane. However, in superficial transitional cell carcinoma, the staining was also seen on the plasma membrane. The pattern of the localization of this antigen in this carcinoma was influenced by the treatment of organic solvents. Electron microscopical observations confirmed that this antigen was localized on the plasma membrane and also in the Golgi apparatus of the superficial tumour. These results proved that the type 3 chain of blood group A is present in human bladder epithelium and low grade tumours in correspondence with the blood type, but disappears in tumours with high malignant potential. However, its expression is independent of the expressions of the other subtypes which have been studied. Furthermore, the changes in the staining pattern caused by pretreatment with organic solvents suggested possible differences in the microenvironment of the glycolipids containing this type of sugar chain. PMID- 7797430 TI - Changes in presence of a segmental dysfunction pattern associated with hypertension: Part 2. A long-term longitudinal study. AB - The short-term portion of this study (part 1) showed an association between somatic dysfunction and the regulation of blood pressure. To study long-term relationships, follow-up examinations were made of 61 subjects studied 3 to 10 years earlier. They were heterogeneous Family Practice Clinic patients with a mean age of 45 years. By methods used in part 1 and in our previous studies of systemic interactions, palpatory examination was done to support presence or absence of a C6T2T6 pattern of segmental motion dysfunctions, and blood pressure status was established by the medical history. The C6T2T6 pattern persisted in 16 of 16 subjects with grade 2 or greater hypertension and 4 of 9 normotensive subjects who had shown the pattern initially. At follow-up, the pattern first appeared in 7 subjects who had hypertension previously diagnosed and who remained hypertensive; the pattern disappeared in 5 normotensive subjects who remained normotensive. The C6T2T6 pattern's long-term persistence in hypertensive subjects and changes in its presence corresponding to the subjects' hypertensive status indicate an important relationship between this pattern of segmental motion dysfunctions and disturbances in regulation of blood pressure. PMID- 7797431 TI - Nerve compression syndromes as models for research on osteopathic manipulative treatment. AB - Experimental and clinical studies of nerve compression syndromes show that ischemia or edema, singly or combined, causes responses in nerves that lead to alterations in impulse conduction and to commonly observed clinical signs. Because osteopathic manipulative treatment (OMT) is thought to affect microcirculation and anatomic positioning of structures, nerve compression syndromes appear ideal as models for studying how OMT accomplishes results. We recommend that researchers develop experimental protocols or clinical studies of nerve compression syndromes that will use anatomic, histologic, and physiologic criteria to monitor the effects of OMT. Techniques such as soft tissue, muscle energy, counterstrain, or myofascial release are appropriate for study in nerve compression syndromes. Such studies are necessary to understand the biologic basis of OMT. PMID- 7797432 TI - Making sense of federal GME reforms: the need for secondary reforms. AB - Physician workforce issues in the healthcare reform debate have led to considerable agreement on the need to reform graduate medical education (GME) in order to control the cost, mix and supply of physician manpower. The osteopathic medical profession's infrastructure is ill-prepared to respond to many of the changes that policymakers are suggesting. In last month's issue, the author reviewed the Gephardt and Mitchell bills, which emerged during the last Congress, identified the reforms recommended for GME, and examined the elements of agreement between the bills. The position of osteopathic medicine vis-a-vis healthcare reform was explored and distinctions between the two bills were drawn. In this article, the author recommends comprehensive secondary reforms in the osteopathic medical profession's three institutions--its colleges, its hospitals, and its political organization, the American Osteopathic Association. PMID- 7797433 TI - 'But doctor, someone has to do something': resolving interpersonal conflicts in the workplace. AB - Physicians are often called on to address interpersonal conflicts among office staff and colleagues. Because such strife can interfere with patient care, physicians should learn to diffuse these situations as adeptly and quickly as possible. The authors outline one approach, which they developed while working at the Oklahoma Department of Mental Health. Designated by the mnemonic LIFT (Listen, Inquire, ask for Feedback, Test), this approach has been used successfully to resolve interpersonal conflict in small groups. PMID- 7797434 TI - The discovery of australifungin, a novel inhibitor of sphinganine N acyltransferase from Sporormiella australis. Producing organism, fermentation, isolation, and biological activity. AB - Potent antifungal activity was detected in fermentation extracts of Sporormiella australis and two related components were isolated from solid fermentations using silica gel and high speed countercurrent chromatography. The most active antifungal component, australifungin, contained a unique combination of alpha diketone and beta-ketoaldehyde functional groups. Australifungin exhibited broad spectrum antifungal activity against human pathogenic fungi with MICs against Candida spp., Cryptococcus neoformans, and Aspergillus spp. between 0.015 and 1.0 microgram/ml. Mode of action studies revealed that australifungin interfered with fungal lipid metabolism by specifically inhibiting sphingolipid synthesis at the step converting sphinganine to ceramide. PMID- 7797436 TI - AKD-2A, B, C and D, new antibiotics from Streptomyces sp. OCU-42815. Taxonomy, fermentation, isolation, structure elucidation and biological activity. AB - An antibiotic complex, AKD-2, was isolated from the mycelial cake of Streptomyces sp. OCU-42815. The lipophilic substances in this complex were further purified by a recycling HPLC procedure and were designated AKD-2A, C and D. AKD-2B was obtained as a mixture of AKD-2B1 and AKD-2B2. These substances were identified as monoglycerides having branched chain fatty acids and exhibited both antibacterial and antifungal activities. PMID- 7797435 TI - Trachyspic acid, a new metabolite produced by Talaromyces trachyspermus, that inhibits tumor cell heparanase: taxonomy of the producing strain, fermentation, isolation, structural elucidation, and biological activity. AB - Trachyspic acid, a new metabolite that inhibited heparanase, was isolated from the culture broth of Talaromyces trachyspermus SANK 12191. Its structure was deduced from NMR spectral analyses and chemical reactions as a tricarboxylic acid derivative containing a spiroketal. The IC50 value of trachyspic acid against heparanase was 36 microM. PMID- 7797437 TI - Phenamide, a fungicidal metabolite from Streptomyces albospinus A19301. Taxonomy, fermentation, isolation, physico-chemical and biological properties. AB - A new derivative of phenylalanine, phenamide, was discovered from the fermentation broth of an actinomycete identified as a member of the Streptomyces albospinus cluster. Phenamide was purified using successive C18 reverse phase and cation exchange chromatography. Its structure was determined by spectroscopic and chemical methods. Its molecular formula, C14H20N2O3, was determined by HRFAB-MS. Phenamide showed activity against Septoria nodorum, the causal agent of wheat glume blotch. PMID- 7797438 TI - Isolation, characterization and structure of a new allenic polyine antibiotic produced by fungus LL-07F275. AB - Antibiotic 07F275 (1), produced by submerged fermentations of fungal culture LL 07F275, was isolated and characterized despite its inherent instability. Its UV spectrum was identical with that of nemotin, a member of the allenic polyacetylene family, but a molecular weight of 218 daltons indicated a new compound. Structure 1 was determined on the basis of spectroscopic evidence, particularly NMR. Since 1 is a thirteen carbon-containing allenic diyne, it is closely related to mycomycin. PMID- 7797439 TI - Simple aromatics identified with a NFAT-lacZ transcription assay for the detection of immunosuppressants. AB - Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic. PMID- 7797440 TI - Inhibition of phosphatidylinositol-specific phospholipase C activity by fluvirucin B2. AB - We isolated fluvirucin B2 from the culture broth of Streptomyces as an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). It inhibited PI-PLC of A431 cell cytosol with an IC50 of 1.6 micrograms/ml. Fluvirucin B2 also inhibited PI-PLC in cultured A431 cells, whereas it did not inhibit phosphatidylinositol synthesis and macromolecular synthesis markedly. It also inhibited epidermal growth factor-induced rapid rounding of A431 cells, in which PI turnover is involved. PMID- 7797441 TI - Structures and absolute configurations of antibiotics of the oligosporon group from the nematode-trapping fungus Arthrobotrys oligospora. AB - Spectroscopic data define the structures of three new antibiotics, 4',5'-dihydro oligosporon (4), hydroxyoligosporon (5) and 10',11'-epoxyoligosporon (6) from the nematode-trapping fungus Arthrobotrys oligospora, and confirm the structures of the recently reported antibiotics oligosporon (1) and oligosporol B (3). The absolute configuration of the substituted 7-oxabicyclo[4.1.0]hept-3-ene nucleus of these metabolites is determined by circular dichroic spectroscopy. Oligosporon (1) and its dihydro-derivative (4) represent the second and most complex structural type of nematocidal metabolite to be characterised from cultures of nematophagous fungi. PMID- 7797442 TI - Synthesis of novel 6-alpha and 6-beta-alkylcarbonylmethyl substituted penems. AB - 6-alpha and 6-beta Alkylcarbonylmethyl penems were synthesized from 6-alpha-bromo and 6-oxo penicillanates respectively and their in vitro antibacterial activity was studied. The compounds were generally active against Gram-positive but not against Gram-negative strains, the compounds of the 6-beta series being more active. Relatively to imipenem, taken as reference compound, the penems resulted more stable towards chemical hydrolysis in Tris-HCl buffered medium (pH 7.4) but more sensitive towards dehydropeptidase-I (DHP-I). PMID- 7797443 TI - Structural features resulting in convulsive activity of carbapenem compounds: effect of C-2 side chain. AB - The neurotoxicity of meropenem was much lower than that of both imipenem and panipenem after intraventricular administration to mice. To clarify the major structural features responsible for the induction of convulsions by carbapenem antibiotics, the structure-activity relationship on convulsant activity was investigated in N-acetyl-2-pyrroline and cyclopentene derivatives which correspond to the 5-membered ring containing the C-2 side chain of carbapenem antibiotics. Among these derivatives, compounds with strong basicity in the side chain showed convulsant activity similar to that of the parent carbapenem compounds. In addition to the strength of the basicity of the amino group, the distance from the carboxyl to the amino group and steric crowding around the amino group also appeared to play an important role in the induction of convulsions. The results of gamma aminobutyric acid (GABAA) receptor binding assays indicated that the induction of convulsions was caused predominantly by the inhibition of GABAA-mediated inhibitory transmission. However, the in vivo convulsant activity of some of these compounds did not correlate with their in vitro inhibitory effect on GABAA receptor binding. PMID- 7797444 TI - Structure-activity relationships within a series of C(7) substitutedoxyiminocephalosporins containing the C(3) methylaminopyridiniumthiomethyl substituent. Synthesis and biological properties of BRL 57342 and some close analogues. AB - (6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4 thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent stability to extended spectrum beta-lactamases. This potency is reflected in in vivo efficacy studies. PMID- 7797445 TI - The microbial modification of A58365A, an angiotensin converting enzyme inhibitor. PMID- 7797446 TI - Production of the staurosporine aglycon K-252c with a blocked mutant of the staurosporine producer strain Streptomyces longisporoflavus and by biotransformation of staurosporine with Streptomyces mediocidicus ATCC 13279. PMID- 7797447 TI - Metabolic products of microorganismen. 270. The structures of the exfoliamycins. PMID- 7797448 TI - Siamycins I and II, new anti-HIV peptides: I. Fermentation, isolation, biological activity and initial characterization. PMID- 7797449 TI - Pyralomicins, new antibiotics from Actinomadura spiralis. PMID- 7797450 TI - Life on Club Road. PMID- 7797451 TI - Parenting their adolescents: the experiences of Jordanian immigrant women in California. AB - Having their children enter adolescence presents new demands on the role functions of Jordanian immigrant women in the United States. Such demands require modifications in traditional parenting approaches. The authors attempted to uncover and describe the experiences of Jordanian immigrant mothers (N = 30) in parenting their adolescents in the United States. Content and narrative analysis revealed the dynamic processes that the mothers used in raising their children. They continuously attempted to balance the need for their teens to maintain a Jordanian ethnic identity and the need for them to become integrated into the new community. Their parenting was driven by an attempt to avoid loss of honor and bad reputation. Four aspects of the maternal role emerged from the analysis: mothering through nurturing the adolescents and promoting cultural identity, disciplining for cultural adherence, advocacy and mediation, and vigilant parenting. The findings support a dynamic interplay between cultural and structural conditions in shaping the experiences of Jordanian immigrant women. PMID- 7797452 TI - Jordanian nursing students' interpersonal behaviors. AB - The interpersonal behaviors of Jordanian nursing students (N = 536) in relation to type of nursing program, year and level, and gender were identified. The Fundamental Interpersonal Relations Orientation Behavior Test (Schutz, 1978), a self-report questionnaire, was used to assess six dimensions of interpersonal behavior. The findings indicated that (a) there was no significant difference in the interpersonal behaviors of baccalaureate and diploma program nursing students, (b) male nursing students had more desire to control interpersonal relations than did female nursing students, and (c) third- and fourth-year nursing students had a greater need to associate with and become close to others than did first- and second-year nursing students. These findings have important implications for nursing curricula, the future status of male and female nurses, and the interpersonal relationships of nurses. PMID- 7797453 TI - HIV and AIDS: issues for women in Australia. AB - The major HIV/AIDS-related issues facing women in Australia are outlined. From a global epidemiological perspective, women in Australia have almost gone unscathed by HIV infection. However, the potential for widespread infection cannot be ignored. The greatest threat for the majority of women in Australia is infection through sexual transmission. Although HIV infection is preventable, there are many social and economic factors that may hinder women's efforts to protect themselves. A major result of the global AIDS epidemic for women in Australia has been caring for a family member who has been infected with HIV. When a member of the family, usually a son, develops AIDS and is cared for at home, it is usually his mother who cares for him. She may face many difficult issues that may affect her health and well-being. Thus the small number of women infected with HIV in Australia does not accurately represent the impact the disease has had, and may potentially have, on the women of Australia. PMID- 7797454 TI - Drug advertisements and the medicalization of unipolar depression in women. AB - Unipolar depression occurs twice as frequently among women as among men, and the pharmacological industry maintains a massive advertising campaign that encourages psychiatric professionals to rely on antidepressant medication as the solution to this problem. The pictorial content of drug advertisements shows women as victims of depression. The social problems and situational stresses associated with unipolar depression are never shown, and depression is assumed to be a personal and biological illness, its etiology decontextualized. In these advertisements, women are not offered a choice between medical and nonmedical treatment and are not empowered to become more active participants in their health decisions. Therapists are urged to become alert to this oversimplification. PMID- 7797455 TI - Women and depression. AB - As Western society increases in complexity and becomes more reliant on technology, women who thrive as integrators in interactional modes will face new dilemmas. Many women will view these changes as challenges, but for many other women, who view these changes as threats, the response will be depression. We lay a foundation to an understanding of depression in women, evaluating the current concept of depression and pointing out its limitations. We then review the traditional theories of women's increased vulnerability to depressive disorders, which have failed to explain adequately this phenomenon. A more recent theory of women's depression, based on the self-in-relation theory of women's development, is offered as an alternative. PMID- 7797456 TI - Psychological and sexual well-being, philosophical/spiritual views, and health habits of long-term cancer survivors. AB - The results of a survey on various aspects of quality of life for 191 women who were long-term cancer survivors are presented. We explored six areas--somatic concerns, health habits, psychological state, sexual satisfaction, social/emotional support giving, and philosophical/spiritual view--and whether differences existed in them among the women on the basis of age, educational level, income level, length of survival, location of residence (urban, suburban, or rural), cancer site, and whether a recurrence of the cancer had been experienced. Generally, the women reported good psychological states and relative satisfaction with their sexual lives. However, women who had experienced a recurrence of their cancer, were longer term survivors, or suffered from breast cancer all reported higher levels of somatic concerns. Women with higher levels of education or income and those who had had a recurrence of their cancer indicated a greater willingness to provide social and emotional support to other women newly diagnosed with cancer. Women who had a positive philosophical/spiritual outlook were more likely to have good health habits and be supportive of others. There was no statistically significant variation among the women in either health habits or psychological state for any of the factors considered. PMID- 7797457 TI - Contribution of generalized negative affect to elevated menstrual cycle symptom reporting. AB - We investigated women's belief that they suffered from premenstrual syndrome (PMS) by monitoring patterns of symptom reporting over a 5-week period in relation to the underlying trait of negative affect. We expected that women reporting high negative affect would be more likely to report menstrual cycle distress than those reporting low negative affect. One hundred twenty-one women rated the typical occurrence and severity of premenstrual changes on a retrospective questionnaire and then made daily ratings of their changes for the duration of one cycle. In addition, they completed a questionnaire measuring positive and negative affect. Data analysis revealed a clear subgroup whose retrospective reports of premenstrual change were not substantiated by the cycle of their daily ratings. Although this subgroup also reported more negative affect, the magnitude of the effect was relatively small. The possible contribution of both negative outlook and the meaning of the self-identified label of PMS are discussed. PMID- 7797458 TI - Electronic performance monitoring and social context: impact on productivity and stress. AB - In a laboratory study, the presence of individual- or work-group-level electronic performance monitoring (EPM) was manipulated as participants worked on a data entry task alone, as a member of a noninteracting aggregate, or as a member of a cohesive group. The pattern of results suggested the operation of a social facilitation effect, as highly skilled monitored participants keyed more entries than highly skilled nonmonitored participants. The opposite pattern was detected among low-skilled participants. No signs of social loafing were detected among group-monitored participants. Nonmonitored workers and members of cohesive groups felt the least stressed. The implications of these findings for organizations adopting EPM systems are discussed. PMID- 7797459 TI - How MAP kinases are regulated. PMID- 7797461 TI - A novel type of protein modification by isoprenoid-derived materials. Diphytanylglycerylated proteins in Halobacteria. AB - Previous work from this laboratory has shown that a derivative of [3H]mevalonic acid is incorporated into a number of specific proteins in Halobacterium halobium and Halobacterium cutirubrum and that the major radioactive material released by treatment with methyl iodide was neither farnesyl nor geranylgeranyl compound, which have been generally accepted to be prenyl groups of a number of prenylated proteins found in eukaryotic cells, but an unknown compound (Sagami, H., Kikuchi, A., and Ogura, K. (1994) Biochem. Biophys. Res. Commun. 203, 972-978). In the current study, the unknown compound was prepared in a large amount from H. halobium cells and analyzed by reverse and normal phase high performance liquid chromatographies followed by mass spectrometry. The mass spectrum of this compound exhibited a parent ion peak (M+) at m/z 682, suggesting that it is a 1 methylthio-2,3-di-O-(3',7',11',15'-tetramethylhexadecyl)glycerol (diphytanylglyceryl methylthioether). Diphytanylglyceryl methyl thioether was chemically synthesized, and its mass fragmentation pattern was completely coincident with that of the mevalonic acid-derived material from H. halobium. These results indicate that Halobacteria contains specific proteins with a novel type of modification of a cysteine residue of the proteins with a diphytanylglyceryl group in thioether linkage. PMID- 7797460 TI - Separate signaling mechanisms are involved in the control of STAT protein activation and gene regulation via the interleukin 6 response element by the box 3 motif of gp130. AB - The cytoplasmic receptor sequences required for the transcriptional control via the IL-6 response element (IL-6RE) and the hematopoietin receptor response element (HRRE) in hepatoma cells were defined by transient expression of wild type and mutant granulocyte-colony stimulating factor receptor-gp130 chimeric receptors. gp130 generated two separate transcriptional signals, one of which was directed to IL-6RE and required an intact box 3 motif, and another, which was directed to HRRE and was box 3-independent. The activation of DNA-binding of STAT3 required the same gp130 domains as the IL-6RE response. A box 3-independent activation of STAT proteins was achieved by overexpression of the kinases JAK2 or TYK2. The increase in the DNA-binding activity of STAT proteins, however, did not result in a corresponding increase in transcription via either IL-6RE or HRRE. The data indicate that activation of the DNA-binding potential of STAT proteins via gp130 is not sufficient to achieve transcriptional up-regulation of specific target genes. PMID- 7797463 TI - Sodium dodecyl sulfate-stable complexes between serpins and active or inactive proteinases contain the region COOH-terminal to the reactive site loop. AB - Recently inhibitors of the serpin family were shown to form complexes with dichloroisocoumarine (DCI)-inactivated proteinases under native conditions (Enghild, J. J., Valnickova, Z., Thogersen I., and Pizzo, S. V. (1994) J. Biol. Chem. 269, 20159-20166). This study demonstrates that serpin-DCI/proteinase complexes resist dissociation when analyzed in reduced SDS-polyacrylamide gel electrophoresis. Previously, SDS-stable serpin-proteinase complexes have been observed only between serpins and catalytically active proteinases. The stability of these complexes is believed to result from an acyl-ester bond between the active site Ser195 of the proteinase and the alpha-carbonyl group of the scissile bond in the reactive site loop. We have further analyzed the structure of the SDS stable serpin-proteinase and serpin-DCI/proteinase complexes. The results of these studies demonstrate the presence of the COOH-terminal region of the serpin in both complexes. Since (i) modification of Ser195 does not prevent formation of SDS-stable complexes and (ii) COOH-terminal peptides are present in both complexes, the previously described mechanism does not sufficiently explain the formation of SDS-stable complexes. PMID- 7797464 TI - The p60 tumor necrosis factor (TNF) receptor-associated kinase (TRAK) binds residues 344-397 within the cytoplasmic domain involved in TNF signaling. AB - The p60 form of the tumor necrosis factor (TNF) receptor lacks motifs characteristic of tyrosine or serine/threonine protein kinases. Our recent observations have indicated that a p60 TNF receptor-associated kinase (p60-TRAK) from U-937 cells physically interacts with and causes the phosphorylation of the cytoplasmic domain of the TNF receptor. To define which region of the cytoplasmic domain is necessary for physical interaction with p60-TRAK, we constructed a series of deletions (grouped into three sets delta 1-delta 5, delta 6-delta 12, and delta 13-delta 16) of the p60 cytoplasmic domain, expressed them as glutathione S-transferase (GST) fusion proteins, and used them in affinity precipitations, followed by in vitro kinase assays. Our detailed analysis indicated that a serine-, threonine-, and proline-rich region (residues 243-274, delta 2) and the N-terminal half of the cytoplasmic domain (residues 243-323, delta 3) neither associated with p60-TRAK nor underwent phosphorylation. We found that out of 222 residues (205-426) in the cytoplasmic domain, only 54 (344-397, delta 12) were sufficient for binding p60-TRAK and for phosphorylation of the cytoplasmic domain. A region of approximately 30 residues (397-426) at the C terminal end was found to interfere with optimal binding of the p60-TRAK activity. Thus, our results indicate that the minimal region of the cytoplasmic domain necessary for interacting with p60-TRAK and for phosphorylation resides within the domain previously reported to be needed for signaling the cytotoxic effect of TNF. PMID- 7797462 TI - Nitric oxide activates the glucose-dependent mobilization of arachidonic acid in a macrophage-like cell line (RAW 264.7) that is largely mediated by calcium independent phospholipase A2. AB - Herein, we demonstrate that nitric oxide is a potent (> 20% release) and highly selective inducer of [3H]arachidonic acid mobilization in the macrophage-like cell line RAW 264.7. Treatment of RAW 264.7 cells with (E)-6-(bromomethylene)-3 (1-naphthalenyl)-2H-tetrahydropyran-2-one resulted in the inhibition of the large majority (86%) of nitric oxide-induced [3H]arachidonic acid release into the medium (IC50 < 0.5 microM) and the concomitant inhibition of in vitro measurable calcium-independent phospholipase A2 activity (92% inhibition) without demonstrable effects on calcium-dependent phospholipase A2 activity. Since nitric oxide is a potent stimulator of glycolysis (and therefore glycolytically derived ATP) and since cytosolic calcium-independent phospholipase A2 exists as a catalytic complex comprised of ATP-modulated phosphofructokinase-like regulatory polypeptides and a catalytic subunit, we examined the role of glucose in facilitating nitric oxide-mediated arachidonic acid release. Nitric oxide-induced release of [3H]arachidonic acid possessed an obligatory requirement for glucose, was highly correlated with the concentration of glucose in the medium, and was dependent on the metabolism of glucose. Thus, [3H]arachidonic acid release is coupled to cellular glucose metabolism through alterations in the activity of calcium-independent phospholipase A2. Collectively, these results identify a unifying metabolic paradigm in which the generation of lipid second messengers is coordinately linked to the signalstimulated acceleration of glycolytic flux, thereby facilitating integrated metabolic responses to cellular stimuli. PMID- 7797466 TI - Cleavage at arginine 145 in human blood coagulation factor IX converts the zymogen into a factor VIII binding enzyme. AB - The transition of the factor IX zymogen into the enzyme factor IXa beta was investigated. For this purpose, the activation intermediate factors IX alpha and IXa alpha were purified after cleavage of the Arg145-Ala146 and Arg180-Val181 bonds, respectively. These intermediates were compared for a number of functional properties with factor IXa beta, which is cleaved at both positions. Factor IXa alpha was equal to factor IXa beta in hydrolyzing the synthetic substrate CH3SO2 Leu-Gly-Arg-p-nitroanilide (kcat/Km approximately 120 s-1 M-1) but was less efficient in factor X activation. Factor IX alpha was incapable of generating factor Xa but displayed reactivity toward p-nitrophenol p-guanidinobenzoate and the peptide substrate. The catalytic efficiency, however, was 4-fold lower compared with factor IXa alpha and factor IXa beta. Factor IX alpha and factor IXa beta had similar affinity for the inhibitor benzamidine (Ki approximately 2.5 mM), and amidolytic activity of both species was inhibited by Glu-Gly-Arg chloromethyl ketone and antithrombin III. Unlike factor IXa beta, factor IX alpha was unable to form SDS stable complexes with antithrombin III. Moreover, inhibition of factor IXa beta and factor IX alpha by Glu-Gly-Arg-chloromethyl ketone followed distinct pathways, because factor IX alpha was inhibited in a nonirreversible manner and displayed only minor incorporation of the dansylated inhibitor into its catalytic site. These data demonstrate that the catalytic site of factor IX alpha differs from that of the fully activated factor IXa beta. Factor IX and its derivatives were also compared with regard to complex assembly with factor VIII in direct binding studies employing the immobilized factor VIII light chain. Factor IX alpha and factor IXa beta displayed a 30-fold higher affinity for the factor VIII light chain (Kd approximately 12 nM) than the factor IX zymogen. Factor IXa alpha showed lower affinity (Kd approximately 50 nM) than factor IX alpha and factor IXa beta, which may explain the lower efficiency of factor X activation by factor IXa alpha. Collectively, our data indicate that cleavage of the Arg180-Val181 bond develops full amidolytic activity but results in suboptimal binding to the factor VIII light chain. With regard to cleavage of the Arg145-Ala146 bond, we have demonstrated that this results in the transition of the factor IX zymogen into an enzyme that lacks proteolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797467 TI - Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. AB - Transcriptional induction of genes is an essential part of the cellular response to interferons. To isolate yet unidentified IFN-regulated genes we have performed a differential screening on a cDNA library prepared from human lymphoblastoid Daudi cells treated for 16 h with human alpha/beta interferon (Hu-alpha/beta IFN). In the course of these studies we have isolated a human cDNA which codes for a protein sharing homology with the mouse Rpt-1 gene; it will be referred as Staf-50 for Stimulated Trans-Acting Factor of 50 kDa. Amino acid sequence analysis revealed that Staf-50 is a member of the Ring finger family and contains all the features of a transcriptional regulator able to initiate a second cascade of gene induction (secondary response). Staf-50 is induced by both type I and type II IFN in various cell lines and down-regulates the transcription directed by the long terminal repeat promoter region of human immunodeficiency virus type 1 in transfected cells. These data are consistent with a role of Staf-50 in the mechanism of transduction of the IFN antiviral action. PMID- 7797468 TI - Developmental regulation of elastin production. Expression of tropoelastin pre mRNA persists after down-regulation of steady-state mRNA levels. AB - To assess the mechanisms controlling the developmental regulation of tropoelastin expression in vivo, we developed a reverse-transcription-polymerase chain reaction (RT-PCR) assay to detect tropoelastin pre-mRNA as an indicator of ongoing transcription in intact tissue. RNA was isolated from mid-fetal (early elastogenic), neonatal (peak tropoelastin expression), and adult (very low tropoelastin expression) rat lungs and reverse transcribed, and the cDNA was amplified with intron specific primers. A weak hybridization signal for tropoelastin pre-mRNA was seen in mid-fetal samples, and paralleling the increase in steady-state mRNA levels, a strong signal for pre-mRNA was detected in neonatal samples, indicating transcriptional regulation. Stimulation of fetal lung tropoelastin expression by maternal administration of dexamethasone also led to an increase in pre-mRNA levels. However, signal for tropoelastin pre-mRNA in adult samples was equal to that detected in neonatal samples, even though mRNA levels had dropped about 80-fold. Persistence of tropoelastin transcription in adult tissue was also seen in cell culture models and was verified by nuclear runoff assay. In addition, an RT-PCR assay for alpha 1 (I) procollagen pre-mRNA accurately revealed the known transcriptional regulation of this gene. Our results demonstrate that the induction and maintenance of elastogenesis is controlled by a transcriptional mechanism, whereas, the cessation of tropoelastin expression is controlled by a post-transcriptional mechanism. PMID- 7797465 TI - Isolation and characterization of human casein kinase I epsilon (CKI), a novel member of the CKI gene family. AB - The casein kinase I (CKI) gene family is a rapidly enlarging group whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. We report here the cloning and characterization of a novel isoform of CKI from a human placental cDNA library. The cDNA for this isoform, hCKI epsilon, predicts a basic polypeptide of 416 amino acids and a molecular mass of 47.3 kDa. It encodes a core kinase domain of 285 amino acids and a carboxyl-terminal tail of 123 amino acids. The kinase domain is 53-98% identical to the kinase domains of other CKI family members and is most closely related to the delta isoform. Localization of the hCKI epsilon gene to chromosome 22q12-13 and the hCKI delta gene to chromosome 17q25 confirms that these are distinct genes in the CKI family. Northern blot analysis shows that hCKI epsilon is expressed in multiple human cell lines. Recombinant hCKI epsilon is an active enzyme that phosphorylates known CKI substrates including a CKI-specific peptide substrate and is inhibited by CKI-7, a CKI-specific inhibitor. A budding yeast isoform of CKI, HRR25, has been implicated in DNA repair responses. Expression of hCKI epsilon but not hCKI alpha rescued the slow growth phenotype of a Saccharomyces cerevisiae strain with a deletion of HRR25. Human CKI epsilon is a novel CKI isoform with properties that overlap those of previously described CKI isoforms. PMID- 7797469 TI - Biochemical discrimination between luminal and abluminal enzyme and transport activities of the blood-brain barrier. AB - Luminal and abluminal membrane vesicles derived from bovine brain endothelial cells, the site of the blood-brain barrier, were fractionated in a discontinuous Ficoll gradient. A mathematical analysis was developed to determine the membrane distribution of membrane marker enzyme activities as well as the ratio of luminal to abluminal membrane in each fraction of the gradient. The results of this analysis indicate that gamma-glutamyl transpeptidase and amino acid transport system A are located on the luminal and abluminal membranes, respectively. Conversely, 5'-nucleotidase and alkaline phosphatase activities are evenly distributed between both membranes. Although Na+/K(+)-ATPase activity is primarily located on the abluminal membrane, approximately 25% of the activity is of luminal origin. Na+/K(+)-ATPase activities associated with each membrane showed different ouabain sensitivities, suggesting that different isoenzymes are located in luminal and abluminal membranes. The analytical procedure used in this study provides a quantitative means to determine the distribution of marker enzymes and transport proteins in partially purified membrane vesicle populations. PMID- 7797470 TI - Neutral amino acid transport characterization of isolated luminal and abluminal membranes of the blood-brain barrier. AB - The neutral amino acid carrier composition of luminal and abluminal membranes of the blood-brain barrier has been studied using isolated membrane vesicles. Phenylalanine was carried almost exclusively by a high affinity (Km = 10 +/- 2 microM), Na(+)-independent amino acid transport system, presumably L1 system, that was found to be symmetrically distributed between luminal and abluminal membranes. Inhibition of phenylalanine uptake was used to determine the affinities (Ki values) toward leucine (17 +/- 3 microM), tryptophan (8 +/- 1), 2 aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH) (11 +/- 2), alanine (628 +/- 117), and glutamine (228 +/- 51). Alanine was found to be transported by two Na(+)-dependent transport systems that were located exclusively on the abluminal membrane. Kinetic and inhibition experiments indicated that one of these activities was due to system A, which is probably the main route for Na(+) dependent alanine transport (Km = 0.6 +/- 0.2 mM) under physiological conditions. The other Na(+)-dependent activity was attributed to a B(o,+)-like system based on its sensitivity toward BCH. This latter system showed greater affinity for large neutral amino acids. The affinities of these two transport systems for several other amino acids were also studied. PMID- 7797471 TI - Deletion of the PEST-like region of photosystem two modifies the QB-binding pocket but does not prevent rapid turnover of D1. AB - The rapid turn-over of the D1 polypeptide of the photosystem two complex has been suggested to be due to the presence of a "PEST"-like sequence located between putative transmembrane helices IV and V of D1 (Greenberg, B. M., Gaba, V., Mattoo, A. K. and Edelman, M. (1987) EMBO J. 6, 2865-2869). We have tested this hypothesis by constructing a deletion mutant (delta 226-233) of the cyanobacterium Synechocystis sp. PCC 6803 in which residues 226-233 of the D1 polypeptide, containing the PEST-like sequence, have been removed. The resulting mutant, delta PEST, is able to grow photoautotrophically and give light-saturated rates of oxygen at wild type levels. However electron transfer on the acceptor side of the complex is perturbed. Analysis of cells by thermoluminescence and by monitoring the decay in quantum yield of variable fluorescence following saturating flash excitation indicates that Q-B, but not Q-A, is destabilized in this mutant. Electron transfer on the donor side of photosystem two remains largely unchanged in the mutant. Turnover of the D1 polypeptide as examined by pulse-chase experiments using [35S]methionine was enhanced in the delta PEST mutant compared to strain TC31 which is the wild type control. We conclude that the PEST sequence is not absolutely required for turnover of the D1 polypeptide in vivo although deletion of residues 226-233 does have an effect on the redox equilibrium between QA and QB. PMID- 7797472 TI - Platelet-activating factor induces NF-kappa B activation through a G protein coupled pathway. AB - The capability of platelet-activating factor (PAF) to induce transcription factor activation was examined. In stably transfected Chinese hamster ovary cells expressing the PAF receptor (CHO-PAFR), PAF stimulation resulted in the nuclear expression of a DNA binding activity with specificity to the kappa B sequence. The p50 and p65 proteins, constituents of the prototypic nuclear factor kappa B (NF-kappa B), were identified as components of the DNA protein complexes by antipeptide antibodies in gel supershift as well as UV cross-linking experiments. PAF induced an initial decrease and subsequent increase of cytoplasmic I kappa B alpha levels, accompanied by up-regulation of the I kappa B alpha messenger RNA, a feature of NF-kappa B activation. PAF-induced kappa B binding activity was detected within 15 min after agonist stimulation, peaked at 30-40 min, and remained detectable by 2.5 h. SR 27417, a PAF receptor antagonist, blocked PAF induced kappa B binding activity but not that induced by tumor necrosis factor alpha (TNF alpha). Cholera toxin treatment markedly reduced PAF-induced kappa B binding activity, whereas pertussis toxin had no significant inhibitory effect. Neither of the two toxins affected the kappa B binding activity induced by TNF alpha in the same cells. In addition to the CHO-PAFR cells, PAF stimulated kappa B binding activity in the murine P388D1 macrophage and the human ASK.0 B cell lines that express endogenous PAF receptors. These results imply a potential role of PAF in the regulation of gene expression through a G protein-coupled transcription factor activation pathway. PMID- 7797473 TI - Partial purification and characterization of Arf-sensitive phospholipase D from porcine brain. AB - Phospholipase D (PLD) activity from membranes of cultured cells can be activated by guanosine 5'-O-(3-thiotriphosphate) and the small GTP-dependent protein, Arf. While this activity was readily apparent in membranes from HL60 cells, it was much lower or not observable in membranes from various mammalian tissues. However, extraction of porcine brain membranes with detergent and subsequent chromatography with SP-Sepharose revealed a large peak of Arf-sensitive PLD activity. This activity has been enriched through several steps of chromatography and characterized with respect to size, nucleotide specificity, and sensitivity to different Arf and Arf-like proteins. Hydrodynamic analysis indicated that the enriched PLD had an s20,w of 5.1 and a Stokes radius of 4.3 nm. These parameters indicate that the enzyme has an apparent molecular mass of 95,000 Da. Effective stimulation of the enriched enzyme was achieved with GTP as well as nonhydrolyzable analogs. All of the Arf subtypes tested were effective activators of PLD activity. Arf derived from yeast could activate mammalian PLD but with lower potency. The Arf-related Arl proteins were ineffective. PLD that has been highly enriched retained a requirement for phosphatidylinositol 4,5-bisphosphate for efficient expression of activity. Additionally, the ability of recombinant or purified porcine brain Arf to stimulate PLD activity was reduced relative to impure fractions of Arf activity. Thus, porcine PLD that has been purified about 5,000-10,000-fold is synergistically activated by Arf in combination with other cytosolic components that are described in the accompanying paper (Singer, W. D., Brown, H. A., Bokoch, G. M., and Sternweis, P. C. (1995) J. Biol. Chem. 270, 14944-14950). Taken together, these data suggest that physiological regulation of Arf-sensitive PLD may involve the coordinate assembly of several interacting regulatory subunits. PMID- 7797474 TI - Resolved phospholipase D activity is modulated by cytosolic factors other than Arf. AB - Phospholipase D, which has been extracted from porcine brain membranes and chromatographically enriched 100-fold, was activated better by impure preparations of Arf than by purified or recombinant Arf. Examination of brain cytosol with this enriched preparation of PLD activity revealed at least three stimulatory components. One of these is Arf or the first cytoplasmic factor. A second peak of PLD-stimulating activity (cytoplasmic factor II, CFII) was resolved from Arf by anion exchange and gel filtration. This CFII can be further separated into multiple activities by chromatography with heparin-agarose. The activities were differentiated by their stimulatory properties as measured in the absence or presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) alone and in the presence of added Arf and GTP gamma S. While all of the CFII pools stimulated PLD activity to some degree and showed synergistic activation when administered in conjunction with Arf, they could be classified into two groups with distinct behavior. When used together, pools from the two respective groups showed synergistic activation of PLD. The first set of pools contained the RhoA monomeric G protein. Recombinant RhoA was used to show that it could indeed activate this enriched PLD activity and act synergistically with Arf proteins. A related monomeric G protein, Cdc42, was also effective. The second set of CFII pools were devoid of RhoA and, in contrast to the first group, demonstrated significant stimulating activity in the absence of guanine nucleotides. These data indicate that the PLD activity from brain can be modulated by several cytosolic factors and that Arf-sensitive PLD may represent a complex activity that can be regulated in an interactive fashion by a variety of cellular signaling events. PMID- 7797475 TI - A possible role of ER-60 protease in the degradation of misfolded proteins in the endoplasmic reticulum. AB - Wild-type human lysozyme (hLZM) is secreted when expressed in mouse L cells, whereas misfolded mutant hLZMs are retained and eventually degraded in a pre Golgi compartment (Omura, F., Otsu, M., Yoshimori, T., Tashiro, Y., and Kikuchi, M. (1992) Eur. J. Biochem. 210, 591-599). These misfolded mutant hLZMs are associated with protein disulfide isomerase (Otsu, M., Omura, F., Yoshimori, T., and Kikuchi, M. (1994) J. Biol. Chem. 269, 6874-6877). From the observation that this degradation is sensitive to cysteine protease inhibitors, such as N-acetyl leucyl-leucyl-norleucinal and N-acetyl-leucyl-leucyl-methioninal, but not to the serine protease inhibitors, 1-chloro-3-tosylamido-7-amino-2-heptanone and (p amidinophenyl)methanesulfonyl fluoride, it was suggested that some cysteine proteases are likely responsible for the degradation of abnormal proteins in the endoplasmic reticulum (ER). ER-60 protease (ER-60), an ER resident protein with cysteine protease activity (Urade, R., Nasu, M., Moriyama, T., Wada, K., and Kito, M. (1992) J. Biol. Chem. 267, 15152-15159), was found to associate with misfolded hLZMs, but not with the wild-type protein, in mouse L cells. Furthermore, denatured hLZM is degraded by ER-60 in vitro, whereas native hLZM is not. These results suggest that ER-60 could be a component of the proteolytic machinery for the degradation of misfolded mutant hLZMs in the ER. PMID- 7797476 TI - The activity of COOH-terminal domain phosphatase is regulated by a docking site on RNA polymerase II and by the general transcription factors IIF and IIB. AB - Each cycle of transcription appears to be associated with the reversible phosphorylation of the repetitive COOH-terminal domain (CTD) of the largest RNA polymerase (RNAP) II subunit. The dephosphorylation of RNAP II by CTD phosphatase, therefore, plays an important role in the transcription cycle. The following studies characterize the activity of HeLa cell CTD phosphatase with a special emphasis on the regulation of CTD phosphatase activity. Results presented here suggest that RNAP II contains a docking site for CTD phosphatase that is essential in the dephosphorylation reaction and is distinct from the CTD. This is supported by the observations that (a) phosphorylated recombinant CTD is not a substrate for CTD phosphatase, (b) RNAP IIB, which lacks the CTD, and RNAP IIA are competitive inhibitors of CTD phosphatase and (c) CTD phosphatase can form a stable complex with RNAP II. To test the possibility that the general transcription factors may be involved in the regulation of CTD phosphatase, CTD phosphatase activity was examined in the presence of recombinant or highly purified general transcription factors. TFIIF stimulates CTD phosphatase activity 5-fold. The RAP74 subunit of TFIIF alone contained the stimulatory activity and the minimal region sufficient for stimulation corresponds to COOH-terminal residues 358-517. TFIIB inhibits the stimulatory activity of TFIIF but has no effect on CTD phosphatase activity in the absence of TFIIF. The potential importance of the docking site on RNAP II and the effect of TFIIF and TFIIB in regulating the dephosphorylation of RNAP II at specific times in the transcription cycle are discussed. PMID- 7797477 TI - Gibberellin biosynthesis in gib mutants of Gibberella fujikuroi. AB - The Ascomycete Gibberella fujikuroi synthesizes gibberellins, fujenal, carotenoids, and other terpenoids. Twelve gib mutants, isolated through the modified gibberellin fluorescence of their culture media, were subjected to chemical and biochemical analyses. Two mutants were specifically defective in the hydroxylation of carbon 13; their total gibberellin production was normal, but their main gibberellin was GA7 instead of GA3. Four mutants were blocked in the early reactions between geranylgeranyl pyrophosphate and 7-hydroxy-kaurenoic acid; two of them could not synthesize kaurene and another one was blocked in several oxidative steps. Six mutants had partial defects in early reactions, leading to the production of one-fifth to one-third of the wild type amounts of gibberellins and fujenal. Two of these produced considerable amounts of kaurenolides due to a defect in the conversion of kaurenoic acid to 7 hydroxykaurenoic acid. Another one produced no carotenoids, but attempts to isolate mutants of reactions shared by the carotenoid and gibberellin pathways failed. The gib mutations did not modify the ability of the fungus to live as a saprophyte. PMID- 7797478 TI - Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor. AB - The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) binds insulin-like growth factor II (IGF-II) with high affinity. To localize the IGF-II binding site within the 15 repeating units that form the extracytoplasmic domain of the receptor, purified human M6P/IGF-II receptor was digested with thermolysin, and the fragments were analyzed for their ability to bind 125I-IGF-II in a cross-linking assay. Two IGF-II-binding receptor fragments of 23 and 37 kDa were purified. Sequence analysis revealed that the fragments consist of disulfide connected peptides comprising amino acids 1331-1566 and 1331 1697 of the receptor repeats 9-12. In a second approach we expressed truncated forms of the M6P/IGF-II receptor fused to the C terminus of the extracytoplasmic domain of the 46-kDa mannose 6-phosphate receptor. Fusion proteins containing M6P/IGF-II receptor repeats 10-15, 10-11, or 11-15 bound IGF-II, whereas a fusion protein containing the single repeat 10 failed to bind. This result indicates that repeat 11 (amino acids 1508-1650) is sufficient for binding of IGF-II. Residues 1508-1566, which are shared by the 23-kDa IGF-II-binding fragment and repeat 11, are proposed to form the IGF-II binding site of the M6P/IGF-II receptor. PMID- 7797480 TI - Identification and functional characterization of an erythroid-specific enhancer in the L-type pyruvate kinase gene. AB - The rat L-type pyruvate kinase gene is transcribed either from promoter L in the liver or promoter L' in erythroid cells. We have now cloned and functionally characterized an erythroid-specific enhancer, mapped in the fetal liver as hypersensitive site B (HSSB) at 3.7 kilobases upstream from the promoter L'. Protein-DNA interactions were examined in the 200-base pair core of the site by in vivo footprinting experiments. In the fetal liver, footprints were revealed at multiple GATA and CACC/GT motifs, whose association is the hallmark of erythroid specific regulatory sequences. Functional analysis of the HSSB element in transgenic mice revealed properties of a cell-restricted enhancer. Indeed, this element was able to activate the linked ubiquitous herpes simplex virus thymidine kinase promoter in erythroid tissues. The activation was also observed in a variety of nonerythroid tissues known to synthesize GATA-binding factors. In the context of L'-PK transgenes, HSSB was not needed for an erythroid-specific activation of the L' promoter, while it was required to stimulate the L' promoter activity to a proper level. Finally, HSSB cannot be replaced by strong ubiquitous viral or cellular enhancers, suggesting a preferential interaction of the HSSB region with the L' promoter. PMID- 7797479 TI - Phosphorylation of CTP synthetase from Saccharomyces cerevisiae by protein kinase C. AB - Phosphorylation of CTP synthetase (EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)) from Saccharomyces cerevisiae protein kinase C was examined. Using pure CTP by synthetase as a substrate, protein kinase C activity was dose- and time-dependent and required calcium, diacylglycerol, and phosphatidylserine for full activation. Protein kinase C activity was also dependent on the concentration of CTP synthetase. Protein kinase C phosphorylated CTP synthetase on serine and threonine residues in vitro whereas the enzyme was primarily phosphorylated on serine residues in vivo. Phosphopeptide mapping analysis of CTP synthetase phosphorylated in vitro and in vivo indicated that the enzyme was phosphorylated on more than one site. Most of the phosphopeptides derived from CTP synthetase phosphorylated in vivo were the same as those derived from CTP synthetase phosphorylated by protein kinase C in vitro. The stoichiometry of the phosphorylation of native CTP synthetase was 0.4 mol of phosphate/mol of enzyme whereas the stoichiometry of the phosphorylation of alkaline phosphatase-treated CTP synthetase was 2.2 mol of phosphate/mol of enzyme. This indicated that CTP synthetase was purified in a phosphorylated state. Phosphorylation of CTP synthetase resulted in a 3-fold activation in enzyme activity whereas alkaline phosphatase treatment of CTP synthetase resulted in a 5-fold decrease in enzyme activity. Overall, the results reported here were consistent with the conclusion that CTP synthetase was regulated by protein kinase C phosphorylation. PMID- 7797481 TI - Topoisomerase II binds to ellipticine in the absence or presence of DNA. Characterization of enzyme-drug interactions by fluorescence spectroscopy. AB - Although a number of drugs currently in use for the treatment of human cancers act by stimulating topoisomerase II-mediated DNA breakage, little is known regarding interactions between these agents and the enzyme. To further define the mechanism of drug action, interactions between ellipticine (an intercalative drug with clinical relevance) and yeast topoisomerase II were characterized. By utilizing a yeast genetic system, topoisomerase II was identified as the primary cellular target of the drug. Furthermore, ellipticine did not inhibit enzyme mediated DNA religation, suggesting that it stimulates DNA breakage by enhancing the forward rate of cleavage. Finally, ellipticine binding to DNA, topoisomerase II, and the enzyme-DNA complex was assessed by steady-state and frequency domain fluorescence spectroscopy. As determined by changes in fluorescence intensity and emission maximum wavelength, and by lifetime analysis, only the protonated species of ellipticine bound to a double-stranded 40-mer oligonucleotide containing a topoisomerase II cleavage site (KD approximately 65 nM). In contrast, predominantly deprotonated ellipticine bound to the enzyme.DNA complex (KD approximately 1.5 microM) or to the enzyme in the absence of nucleic acids (KD approximately 160 nM). These findings suggest that ellipticine interacts directly with topoisomerase II and that the enzyme dictates the ionic state of the drug in the ternary complex. A model is presented in which the topoisomerase II.ellipticine.DNA complex is formed via initial drug binding to either the enzyme or DNA. PMID- 7797482 TI - Structural analysis of the mannan region of lipoarabinomannan from Mycobacterium bovis BCG. Heterogeneity in phosphorylation state. AB - Lipoarabinomannan (LAM) is a major antigen of mycobacterial cell walls, involved in host-Mycobacterium interactions. In a previous work, LAM from the vaccine strain, Mycobacterium bovis BCG, was found to exhibit mannooligosaccharides at its arabinan nonreducing ends (ManLAM). The present report concerns the mannan core structure of this ManLAM. After partial hydrolysis of ManLAM, two populations of mannans (Ma1 and Ma2) were obtained by gel filtration chromatography. Their structural features were defined by means of two dimensional homo- and heteronuclear (1H-13C) NMR sequences and methylation analysis. They were both found to be composed of an alpha-(1-->6)-linked mannan backbone with alpha-(1-->2)-Manp-linked side chains. They are highly branched, and Ma2 presents a higher frequency of branching than Ma1. Moreover, chemical analysis indicates that only Ma1 is phosphorylated. By a two-dimensional heteronuclear 1H-31P total correlation experiment, the phosphate was found to be involved in a phosphodiester bond between inositol C-1 and glycerol C-3. Then, the molecular mass of mannan was established by mass spectrometry, which revealed a molecular mass of 3517 Da for the major molecular species of Ma1. Likewise, analysis of unfractionated mannans showed the occurrence of other, quantitatively minor molecular species, endowed with two phosphates. This study clearly indicates that the mannan region of M. bovis BCG ManLAM exists as a heterogeneous population of molecules whose structures differ in their degree of glycosylation, level of branching, and phosphorylation state. The hypothesis that the relative abundance of these different molecules modulates the biological functions of LAM is discussed. PMID- 7797485 TI - VMA8 encodes a 32-kDa V1 subunit of the Saccharomyces cerevisiae vacuolar H(+) ATPase required for function and assembly of the enzyme complex. AB - The isolated Saccharomyces cerevisiae vacuolar proton-translocating ATPase (V ATPase) is composed of at least 10 subunits. We have identified VMA8, the gene encoding the 32-kDa subunit of the V-ATPase, by 100% match between the sequences of tryptic peptides and the predicted protein sequence of ORF11. The VMA8 gene contains a 768-base pair open reading frame encoding a 256-amino acid protein with a predicted molecular mass of 29,176 Da. Disruption of VMA8 resulted in a mutant exhibiting pH-sensitive growth, slowed growth under all conditions, and an inability to grow on nonfermentable carbon sources. Vacuolar membranes isolated from vma8 delta yeast cells exhibited no V-ATPase activity. Immunoblot analysis of vma8 delta cells revealed normal levels of both V1 and Vo subunits. Whereas the V1 subunits failed to associated with the vacuolar membrane in vma8 delta cells, the Vo polypeptides were transported to and stable in the vacuolar membrane. Density gradient fractionation revealed that Vma8p associated only with the fully assembled V-ATPase and did not associate with a separate lower density Vo subcomplex fraction. Finally, Vma8p was unable to assemble onto the vascular membranes in the absence of other V1 subunits. PMID- 7797483 TI - gp180, a host cell glycoprotein that binds duck hepatitis B virus particles, is encoded by a member of the carboxypeptidase gene family. AB - Duck hepatitis B virus particles bearing the L and S envelope proteins bind a cellular glycoprotein of 180 kDa (gp180) with high affinity and specificity. Binding is mediated by the pre-S region of the L protein and is blocked by neutralizing but not by non-neutralizing monoclonal antibodies to the virus. These and other properties have suggested that gp180 may be a component of the viral entry machinery. Here we report the purification of gp180 from duck liver and the isolation and characterization of cDNA encoding it. DNA sequence analysis of this cDNA indicates that gp180 is a novel member of the basic carboxypeptidase gene family. PMID- 7797484 TI - 5-Oxo-eicosanoids are potent eosinophil chemotactic factors. Functional characterization and structural requirements. AB - Human eosinophils produce upon treatment with 5-oxo-eicosatetraenoic acid or (5S,15S)-dihydroxyeicosatetraenoic acid a potent eosinophil-chemotactic eicosanoid, 5-oxo-15-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoi c acid (5-oxo-15 HETE). 5-Oxo-15-HETE induces human eosinophil (Eo) chemotaxis at nanomolar concentrations with an efficacy in vitro comparable to that seen for platelet activating factor. Comparison of Eo chemotactic activities of several structurally related eicosanoids with different substituents and/or double bound geometry led to the conclusion that maximal potency and efficacy of eosinophil chemotactic and chemokinetic activity is present in 5-oxo-(6E,8Z,11Z,14Z) eicosatetraenoic acid (5-oxo-ETE). The presence of a hydroxyl group at position C 15 is not necessary for potent chemotactic activity, whereas a geometric isomer having trans instead of cis double bond at C-atom 8, as well as esterified 5-oxo ETE usually show a 5-10-fold lower potency. 5-Oxo-eicosanoids elicit a dose dependent transient rise of intracellular Ca2+ levels in human Eos, however, in contrast to some other Eo chemotaxins do not induce degranulation. Cross desensitization of Ca2+ mobilization and Eo chemotaxis revealed that the geometric isomers of 5-oxo-eicosanoids, 5(S)-HETE, and (5S,15S)-di-HETE cross deactivate Eo responses to each other, whereas other, unrelated stimuli did not interfere with these lipids indicating that 5-oxo-eicosanoids activate Eos via a separate receptor. PMID- 7797486 TI - Characterization of the enhanced transport of L- and D-lactate into human red blood cells infected with Plasmodium falciparum suggests the presence of a novel saturable lactate proton cotransporter. AB - Human erythrocytes parasitized with the malarial protozoan Plasmodium falciparum showed rates of L-lactate, D-lactate, and pyruvate uptake many fold greater than control cells. Thus it was necessary to work at 0 degrees C to resolve true initial rates of transport. Studies on the dependence of the rate of transport on substrate concentration implied the presence in parasitized cells of both a saturable mechanism blocked by alpha-cyano-4-hydroxycinnamate (CHC) and a nonsaturable mechanism insensitive to CHC. The former was dominant at physiological substrate concentrations with Km values for pyruvate and D-lactate of 2.3 and 5.2 mM, respectively, with no stereoselectivity for L- over D-lactate. CHC was significantly less effective as an inhibitor of lactate transport in parasitized erythrocytes than in uninfected cells, whereas p chloromercuribenzenesulfonate, a potent inhibitor in control cells, gave little or no inhibition of lactate transport into parasitized erythrocytes. Inhibition of transport into infected cells was also observed with phloretin, furosemide, niflumic acid, stilbenedisulfonate derivatives, and 5-nitro-2-(3 phenylpropylamino)benzoic acid at concentrations similar to those that inhibit the lactate carrier of control erythrocytes. These compounds were more effective inhibitors of the rapid transport of chloride into infected cells than of lactate transport, whereas CHC was more effective against lactate transport. This implies that different pathways are involved in the parasite-induced transport pathways for lactate and chloride. The transport of L-lactate into infected erythrocytes was also inhibited by D-lactate, pyruvate, 2-oxobutyrate, and 2-hydroxybutyrate. The intracellular accumulation of L-lactate at equilibrium was dependent on the transmembrane pH gradient, suggesting a protogenic transport mechanism. Our data are consistent with lactate and pyruvate having direct access to the malarial parasite, perhaps via the proposed parasitophorous duct or some close contact between the host cell and parasite plasma membranes, with transport across the latter by both a proton-linked carrier (CHC-sensitive, saturable, and the major route) and free diffusion of the undissociated acid (CHC-insensitive, unsaturable, and a minor route). PMID- 7797488 TI - Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms. AB - The 121-amino acid form of vascular endothelial growth factor (VEGF121) and the 165-amino acid form (VEGF165) are mitogenic for vascular endothelial cells and induce angiogenesis in vivo. VEGF165 possesses a heparin binding ability and in the absence of heparin-like molecules does not bind efficiently to the VEGF receptors of vascular endothelial cells. The binding of 125I-VEGF165 to the VEGF receptors of endothelial cells, and the heparin-dependent binding of 125I-VEGF165 to a soluble extracellular domain of the VEGF receptor KDR/flk-1, were inhibited by the angiogenesis inhibitor platelet factor-4 (PF4). In contrast, PF4 was not able to inhibit the binding of VEGF121, a VEGF isoform which lacks a heparin binding capacity, to the VEGF receptors of the cells or to KDR/flk-1. These results indicate that PF4 may inhibit VEGF165 binding to VEGF receptors by disrupting the interaction of VEGF165 with cell surface heparan sulfates. Since PF4 mutants lacking a heparin binding ability retain their anti-angiogenic activity, alternative inhibitory mechanisms were also examined. 125I-PF4 bound with high affinity (Kd 5 x 10(-9) M) to VEGF165-coated wells. The binding of 125I PF4 to the VEGF165-coated wells was inhibited by several types of heparin binding proteins, including unlabeled PF4 and unlabeled VEGF165. The binding was not inhibited by proteins which lack a heparin binding capacity, nor was it inhibited by VEGF121. Heparinase did not inhibit the binding of 125I-PF4 to VEGF165, indicating that heparin-like molecules are not required. These experiments suggest that PF4 can bind to heparin binding proteins such as VEGF165 leading to an inhibition of their receptor binding ability. In agreement with these results, we have observed that PF4 inhibits efficiently the VEGF165 induced proliferation of vascular endothelial cells. Unexpectedly, PF4 also inhibited efficiently the VEGF121-induced proliferation of the cells, indicating that PF4 can disrupt VEGF receptor mediated signal transduction using an unknown mechanism which does not interfere with VEGF121 binding. PMID- 7797487 TI - Cloning, bacterial expression, and characterization of the Mason-Pfizer monkey virus proteinase. AB - We have cloned and expressed the 3' region of the Mason-Pfizer monkey virus pro gene in Escherichia coli. The recombinant 26-kDa precursor undergoes rapid self processing both in E. coli and in vitro at the NH2 terminus, yielding a proteolytically active 17-kDa protein, p17. This initial cleavage is followed in vitro by a much slower self-processing that leads to emergence of proteolytically active p12 and a COOH-terminal cleavage product p5. We have found the NH2 terminal processing site of both the p17 and p12 to be identical and similar to the amino terminus of the mouse mammary tumor virus proteinase. We have also identified the COOH-terminal processing site of the p12 form. Using purified recombinant proteins and synthetic oligopeptide substrates based on naturally occurring retroviral processing sites, we have determined the enzymatic activity and specificity of the Mason-Pfizer monkey virus proteinase to be more closely related to that of myeloblastosis-associated virus proteinase rather than that of the Human immunodeficiency virus type 1 proteinase. Inhibition studies using peptide inhibitors support these results. PMID- 7797489 TI - Expression screening reveals an orphan receptor chick ovalbumin upstream promoter transcription factor I as a regulator of neurite/substrate-cell contacts and cell aggregation. AB - A rat homologue of chick ovalbumin upstream promoter transcription factor I (COUP TF I) was isolated using an expression cloning method developed to isolate neurite outgrowth inhibitors. Overexpression of COUP-TF I in 3T3 fibroblasts resulted in reduction of stable contact formation between neurites and transfected cells. Additionally, COUP-TF I enhanced retinoic acid response element-dependent reporter gene expression in 3T3 fibroblasts, indicating that COUP-TF I can modulate transcriptional activation in these cells. Our data suggest that COUP-TF transcription factors are involved in the regulation of cell surface molecules during neruogenesis. PMID- 7797491 TI - Thermodynamics of fatty acid binding to fatty acid-binding proteins and fatty acid partition between water and membranes measured using the fluorescent probe ADIFAB. AB - Using the fluorescent probe ADIFAB (acrylodan-derivatized intestinal fatty acid binding protein) to determine the equilibrium concentration of the free (unbound) fatty acid (FFA), dissociation constants were measured between 10 and 50 degrees C for the interaction of five different long chain fatty acids (FA) with fatty acid-binding proteins (FABP) from adipocyte, intestine, and heart. Gibbs free energies (delta G) determined from the dissociation constants were between about 9 and -11 kcal/mol at 25 degrees C. Thermodynamic parameters for binding were determined using van't Hoff plots of the dissociation constants, which range, over the entire temperature region, between 2 and 3000 nM. For all the unlabeled FABPs, free energies of binding were dominated by large negative enthalpies that ranged from -7 to -12 kcal/mol, and the enthalpies tended to decrease with increasing FA unsaturation. The entropic contributions (-T detla S) at 25 degrees C between -4 and +2 kcal/mol and tended to increase with increasing FA unsaturation. To assess the role of FA aqueous solubility in FABP binding, measurements of the partition of FA between unilamellar lipid vesicles and water were also done using ADIFAB; the lipid/water partition coefficients (Kp) determined from these measurements were found to be independent of temperature. The binding of FA to FABP is governed by the sum of contributions of various interactions between FA, water, and FABP. An analysis of the individual contributions suggests that the net free energy of binding results from the canceling in part of a number of separate quite large contributions. The entropic contributions sum almost to zero for most FA and FABPs as a result of the canceling of a large increase in bulk solvent entropy by decreases in configurational entropy upon FA binding to FABP. The net, approximately -10 kcal/mol enthalpy of binding, probably results from an increase in FA configurational enthalpy upon binding to FABP plus a large negative enthalpy from the interaction between the FA and the FABP. This large enthalpy of the FA-FABP interaction suggests that in addition to previously identified specific interactions between the carboxylate portion of the FA and charged amino acids within the binding cavity, other significantly larger enthalpic interactions, presumably involving the hydrocarbon portion of the FA, must contribute to the binding energy. PMID- 7797490 TI - Catalytic cleavage of an RNA target by 2-5A antisense and RNase L. AB - 2-5A antisense (2-5A-AS) molecules are chimeric oligonucleotides that cause 2-5A dependent RNase (RNase L) to catalyze the selective cleavage of RNA in human cells. These composite nucleic acids consist of a 5'-monophosphorylated, 2',5' linked oligoadenylate known as 2-5A (an activator of RNase L) covalently attached to antisense 3',5'-oligodeoxyribonucleotides. Here, we characterize the targeted cleavage of the double-stranded RNA-dependent protein kinase (PKR) mRNA by purified, recombinant human RNase L. A 2-5A-AS chimera, which contains complementary sequence to PKR mRNA, and unmodified 2-5A, which causes general RNA decay, were about 20- and 40-fold more active, respectively, than 2-5A-AS chimeras in which the DNA domains are not complementary to sequences in PKR mRNA. Directed cleavage was efficient because each 2-5A-AS chimera targeted many RNA molecules. Moreover, RNase L caused the catalytic cleavage of the RNA target (kcat of approximately 7 s-1). The precise sites of PKR mRNA cleavage caused by 2 5A-AS were mapped, using a primer extension assay, to phosphodiester bonds adjacent to the 3' terminus of the chimera binding site (5' on the RNA target) as well as within the chimera's oligonucleotide binding site itself. The selectivity of this approach is shown to be provided by the antisense arm of the chimera, which places the RNA target in close proximity to the RNase. PMID- 7797492 TI - Role of the endoplasmic reticulum chaperone calnexin in subunit folding and assembly of nicotinic acetylcholine receptors. AB - The nicotinic acetylcholine receptor (AChR) is a pentameric complex assembled from four different gene products by mechanisms that are inadequately understood. In this study we investigated the role of the endoplasmic reticulum (ER)-resident molecular chaperone calnexin in AChR subunit folding and assembly. We have shown that calnexin interacts with nascent AChR alpha-subunits (AChR-alpha) in muscle cell cultures and in COS cells transfected with mouse AChR-alpha. In chick muscle cells maximal association of labeled alpha-subunits with calnexin was observed immediately after a 15-min pulse with [35S]methionine/cysteine and subsequently declined with a t1/2 of approximately 20 min. The decrease in association with calnexin was concomitant with the folding of the alpha-subunit to achieve conformational maturation shortly before assembly. Brefeldin A did not inhibit AChR subunit assembly or the dissociation of calnexin from the assembling subunits, confirming that the ER is the site of AChR assembly and that calnexin dissociation is not affected under conditions in which the exit of assembled AChR from the ER is blocked. These results indicate that calnexin participates directly in the molecular events that lead to AChR assembly. PMID- 7797494 TI - Low density lipoprotein (LDL) cholesterol is converted to 27-hydroxycholesterol in human fibroblasts. Evidence that 27-hydroxycholesterol can be an important intracellular mediator between LDL and the suppression of cholesterol production. AB - The formation of oxysterols in cultured human fibroblasts and their physiological roles as intracellular regulators of cholesterol production have been investigated. In the presence of low density lipoproteins (LDL) normal fibroblasts converted LDL cholesterol to the oxysterol 27-hydroxycholesterol in quantities apparently sufficient to down-regulate 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The production of 27-hydroxycholesterol started 3 8 h after the addition of LDL to the incubation medium, and during this time the activity of HMG-CoA reductase decreased by 73%. Formation of other biologically active oxysterols such as 7 alpha-hydroxycholesterol, 24-hydroxycholesterol, and 25-hydroxycholesterol was not observed. When 27-hydroxylation of LDL cholesterol in mitochondria was selectively prevented by treating normal fibroblasts with cyclosporin A or by using fibroblasts genetically lacking sterol 27-hydroxylase, the suppressive effect of LDL on HMG-CoA reductase was reduced by a factor of about 10. In the absence of LDL or when the fibroblasts lacked LDL-receptors, the cells did not produce detectable amounts of 27-hydroxycholesterol, and HMG-CoA reductase was up-regulated. The results provide strong evidence that 27 hydroxycholesterol is an important intracellular mediator between LDL and the suppression of HMG-CoA reductase in human fibroblasts. The mitochondrial uptake/metabolism of LDL cholesterol seems to be a biologically important extension of the LDL pathway in human cells, since the mitochondrial products of LDL cholesterol may regulate cholesterol homeostasis or be precursors of steroid hormones or bile acids. This pathway, which has now been demonstrated in fibroblasts, may link together the two 22-year-old observations that LDL as well as oxysterols can down-regulate HMG-CoA reductase in cells. PMID- 7797493 TI - Segmental conservation of sapA sequences in type B Campylobacter fetus cells. AB - Campylobacter fetus cells may exist as either of two defined serogroups (type A or B) based on their lipopolysaccharide (LPS) composition. Wild-type strains contain surface array proteins (S-layer proteins) that have partial antigenic cross-reactivity but bind exclusively to LPS from homologous (type A or B) cells. Type A cells possess 8 homologs of sapA, which encodes a 97-kDa S-layer protein; the gene products of these homologs have a conserved N terminus of 184 amino acids. To further explore the structural relationships between the C. fetus S layer proteins and their encoding genes, we sought to clone and express an S layer protein from type B strain 84-91. The cloned type B gene (sapB) was similar in structure to the previously cloned type A gene (sapA) and encoded a full length 936-amino acid (97-kDa) S-layer protein. Sequence analysis of sapB indicated that the conserved N-terminal encoding region in sapA was absent but that the remainder of the ORF (encoding 751 amino acids) was identical to that of sapA in spite of the nonconserved nature of this region among sapA homologs. Noncoding sequences both 300 base pairs 5' and 1000 base pairs 3' to the sapB and sapA ORFs, including the sapA promoter and transcriptional terminator sequences, were essentially identical. Southern analyses revealed that the sapB N-terminal encoding region was conserved in multiple copies in type B strains but was absent in type A strains. Recombinant sapA and sapB products bound to a substantially greater degree to cells of the homologous LPS type compared with the heterologous LPS type, indicating that the conserved sapA- and sapB-encoded N termini are critical for LPS binding specificity. The parallel genetic organization and identity at the nucleotide level in both coding and noncoding regions for sap homologs in types A and B cells indicates the necessity of both homolog conservation and high fidelity DNA replication in the biology of sap diversity. PMID- 7797495 TI - The fatty acid bimodal action on superoxide anion production by human adherent monocytes under phorbol 12-myristate 13-acetate or diacylglycerol activation can be explained by the modulation of protein kinase C and p47phox translocation. AB - We studied the translocation of protein kinase C (PKC), the endogenous phosphorylation and presence in the membrane fraction of p47phox (the 47-kDa cytosolic component of the phagocyte NADPH oxidase), and the O-.2 production in human adherent monocytes (HAMs). This was performed under phorbol myristate acetate (PMA) or diacylglycerol stimulation after cell preincubation in the presence of either 13-methyltetradecanoate or arachidonate. At 3 nM and 30 microM, both fatty acids had enhancing and depressing effects, respectively, on PKC translocation and O-.2 production strictly depending on the PMA- or diacylglycerol-stimulated state of the cell. Endogenous phosphorylation and membrane presence of p47phox were markedly reinforced in PMA-stimulated HAMs in the presence as compared to the absence of 13-methyltetradecanoate. These results emphasize the fact that in intact cells the capacity of both FAs to potentiate or depress the HAM O-.2 production is mediated by a direct action on the PKC membrane translocation leading to a simultaneous endogenous phosphorylation and membrane translocation of p47phox. They confirm the recent findings (Kadri Hassani, N., Leger, C. L., and Descomps, B. (1995) J. Lipid Med. Cell Signal. 11, 159-173) on the PKC-mediated, adherent monocyte-specific capacity of these fatty acids and others (with the exception of linear saturated fatty acids) to enhance the PMA-stimulated O-.2 production at nanomolar concentrations and to depress it at micromolar concentrations. PMID- 7797496 TI - Transactivation of LAP/NF-IL6 is mediated by an acidic domain in the N-terminal part of the protein. AB - LAP/NF-IL6 is a member of the C/EBP family of transcriptional activators and has been shown to be involved in the regulation of the acute-phase response. We have previously shown that phosphorylation of the liver-enriched transcriptional activator protein (LAP) Ser-105 enhances the activation of LAP-dependent genes. To identify the region which is important for gene activation, a series of LAP mutants were constructed, and domain swapping experiments with the DNA-binding domain of GAL4 were performed. These experiments point to an acidic region located between amino acids 21 and 105 of LAP/NF-IL6 which activates genes independent of the DNA-binding domain and the leucine zipper of LAP/NF-IL6. Computer-assisted predictions reveal two regions, a helical and a hydrophobic region in the transactivation domain, which could be important in mediating the direct interaction with the basal machinery. Site-directed mutagenesis of acidic residues in both regions demonstrates that the hydrophobic region located between amino acids 85 and 95 is the likely motif for the interaction with the basal machinery. Our results demonstrate that a hydrophobic region in the acidic transactivation domain of LAP/NF-IL6 seems to be relevant in mediating gene activation of LAP-dependent genes. PMID- 7797497 TI - Inhibition of low threshold calcium channels by angiotensin II in adrenal glomerulosa cells through activation of protein kinase C. AB - In adrenal glomerulosa cells, low threshold voltage-activated (T-type) calcium channels play a crucial role in coupling physiological variations of extracellular potassium to aldosterone biosynthesis. Angiotensin II markedly reduced the activity of these channels by shifting their activation curve toward positive voltage values. This inhibition of the channels resulted in a marked decrease of the cytosolic free calcium concentration maintained by potassium. This effect was abolished by losartan, a specific antagonist of the angiotensin II AT1 receptor. Hormone action on T-type channels appeared to be mediated by protein kinase C because 1) it was mimicked by phorbol ester and diacylglycerol, and 2) it was significantly reduced by decreasing protein kinase C activity with specific inhibitors such as chelerythrine chloride or a pseudosubstrate of the enzyme, as well as by protein kinase C down-regulation. Similarly, protein kinase C activation reduced the cytosolic calcium response to potassium and the steroidogenic action of this agonist. Low threshold T-type calcium channels therefore appear as potential sites for the modulation of steroidogenesis by protein kinase C in adrenal glomerulosa cells. PMID- 7797498 TI - The neuronal nicotinic acetylcholine receptor alpha 2 subunit gene promoter is activated by the Brn-3b POU family transcription factor and not by Brn-3a or Brn 3c. AB - The regulatory region of the neuronal nicotinic acetylcholine receptor alpha 2 subunit gene, which contains six copies of the octamer-related sequence CCCCATGCAAT, is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This effect is in contrast to the previously documented inhibitory effect of Brn-3b on octamer-containing promoters that are activated by Brn-3a and Brn-3c. Activation of the alpha 2 gene by Brn-3b requires that both the POU domain and other N-terminal sequences are derived from Brn-3b and is dependent on the intactness of the alpha 2 gene regulatory region, being lost in truncated derivatives containing one, two, or four copies of the octamer-related sequence. Surprisingly, however, these truncated derivatives are activated by Brn-3c. These effects are discussed in terms of both the influence of the target sequence and its context in the promoter on activation by the various forms of Brn-3 as well as of the processes that restrict expression of the alpha 2 subunit gene to a few cells in the nervous system. PMID- 7797499 TI - Alpha-scorpion toxins binding on rat brain and insect sodium channels reveal divergent allosteric modulations by brevetoxin and veratridine. AB - At least six topologically separated neurotoxin receptor sites have been identified on sodium channels that reveal strong allosteric interactions among them. We have studied the allosteric modulation induced by veratridine, binding to receptor site 2, and brevetoxin PbTx-1, occupying receptor site 5, on the binding of alpha-scorpion toxins at receptor site 3, on three different neuronal sodium channels: rat brain, locust, and cockroach synaptosomes. We used 125I-AaH II, the most active alpha-scorpion toxin on vertebrates, and 125I-Lqh alpha IT, shown to have high activity on insects, as specific probes for receptor site 3 in rat brain and insect sodium channels. Our results reveal that brevetoxin PbTx-1 generates three types of effects at receptor site 3:1) negative allosteric modulation in rat brain sodium channels, 2) positive modulation in locust sodium channels, and 3) no effect on cockroach sodium channel. However, PbTx-1 activates sodium channels in cockroach axon similarly to its activity in other preparation. Veratridine positively modulates both rat brain and locust sodium channels but had no effect on alpha-toxin binding in cockroach. The dramatic differences in allosteric modulations in each sodium channel subtype suggest structural differences in receptor sites for PbTx-1 and/or at the coupling regions with alpha-scorpion toxin receptor sites in the different sodium channels, which can be detected by combined application of specific channel modifiers and may elucidate the dynamic gating activity and the mechanism of allosteric interactions among various neurotoxin receptors. PMID- 7797500 TI - The zinc-binding site of Escherichia coli glutamyl-tRNA synthetase is located in the acceptor-binding domain. Studies by extended x-ray absorption fine structure, molecular modeling, and site-directed mutagenesis. AB - The zinc contents of fragments of Escherichia coli glutamyl-tRNA synthetase, as well as the conservation of the CYC sequence only in zinc-containing glutamyl tRNA synthetases, suggested that the 98CYCX24-CRHSHEHHADDEPC138 includes some or all residues involved in binding its zinc atom (Liu, J., Lin, S.-X., Blochet, J. E., Pezolet, M., and Lapointe, J. (1993) Biochemistry 32, 11390-11396). Extended x-ray absorption fine structure (EXAFS) shows that this zinc atom has a four coordinate non-planar coordination environment with 3 sulfur and 1 nitrogen atoms with bond lengths, respectively, 2.37 +/- 0.02 A and 2.01 +/- 0.02 A, presumably belonging to 3 cysteine residues and 1 histidine residue. Conservative replacement of each histidine and cysteine residue of the 98C-138C segment, respectively, with glutamine (Q) and serine (S), yields variants H129Q, H131Q, H132Q, and C138S (which sustain the growth at 42 degrees C of E. coli JP1449, whose glutamyl-tRNA synthetase is thermosensitive) and C98S, C100S, C125S, and H127Q (which do not). The amount of this enzyme in these mutants is at least 1 order of magnitude larger than that in a wild type strain; however, no glutamyl tRNA synthetase activity is detectable in extracts of the variants C100S and C125S, whereas its specific activity in those of C98S and H127Q is about 10-fold lower than in cells overproducing the wild type enzyme or the variants H129Q, H131Q, H132Q, and C138S. These results indicate that the zinc atom present in E. coli glutamyl-tRNA synthetase is bound by the 2 evolutionarily conserved cysteines at positions 98 and 100, and by Cys125 and His127. Molecular modeling of the N-terminal half of this enzyme, using the known structure of E. coli glutaminyl-tRNA synthetase, supports this conclusion and suggests that the 98C 127H segment does not have the characteristics of the classical zinc fingers. PMID- 7797501 TI - G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C. AB - The murine G-protein alpha-subunit G alpha 15 and its human counterpart G alpha 16 are expressed in a subset of hematopoietic cells, and they have been shown to regulate beta-isoforms of inositide-specific phospholipase C. We studied the ability of a variety of receptors to interact with G alpha 15 and G alpha 16 by cotransfecting receptors and G-protein alpha-subunits in COS-7 cells. Activation of beta 2 adrenergic and muscarinic M2 receptors in cells expressing the receptors alone or together with G alpha q, G alpha 11, or G alpha 14 led to a very small stimulation of endogenous phospholipase C. However, when the receptors were coexpressed with G alpha 15 and G alpha 16, addition of appropriate ligands caused a severalfold increase in inositol phosphate production which was time- and dose-dependent. A similar activation of phospholipase C was observed when several other receptors which were previously shown to couple to members of the Gi and Gs family were coexpressed with G alpha 15/16. In addition, stimulation of inositol phosphate formation via receptors naturally coupled to phospholipase C was enhanced by cotransfection of G alpha 15 and G alpha 16. These data demonstrate that G alpha 15 and G alpha 16 are unique in that they can be activated by a wide variety of G-protein-coupled receptors. The ability of G alpha 15 and G alpha 16 to bypass the selectivity of receptor G-protein interaction can be a useful tool to understand the mechanism of receptor-induced G-protein activation. In addition, the promiscuous behavior of G alpha 15 and G alpha 16 toward receptors may be helpful in finding ligands corresponding to orphan receptors whose signaling properties are unknown. PMID- 7797502 TI - Carbohydrate-binding property of peptide: N-glycanase from mouse fibroblast L-929 cells as evaluated by inhibition and binding experiments using various oligosaccharides. AB - Carbohydrate binding to peptide: N-glycanase from mouse fibroblast L-929 cells (L 929 PNGase) and inhibition by oligosaccharides of its catalytic activity were studied. L-929 PNGase was found to bind strongly with oligosaccharides having triomannosido-N,N'-diacetyl-chitobiosyl (Man3GlcNAc2) structure (Kd = approximately 10 microM). This binding was inhibited by mannotriose (Man3; Man alpha 1-->3[Man alpha 1-->6]Man) but not by N,N'-diacetylchitobiose (GlcNAc2; GlcNAc beta 1-->4GlcNAc). Scatchard analysis indicated that there exist two binding sites for Man3 on a homodimeric form of a 105-kDa subunit. Oligosaccharides having Man3GlcNAc2 structure were also shown to be strong inhibitors for the PNGase-catalyzed reaction (Ki = approximately 10 microM). The minimum structural requirements for inhibition of the PNGase activity were Man3 and GlcNAc2. Enzyme kinetic studies showed that the mechanism of inhibition by the oligosaccharides and Man3 fits well with a model wherein two inhibitor binding sites reside on L-929 PNGase. The conformity of Kd with IC50 values may be taken as an evidence for inhibition of the catalytic activity by the oligosaccharides and Man3 through the occupation of the binding sites with these molecules. On the other hand, inhibition by GlcNAc2 followed the simple competitive mode. Since the minimum substrate for the L-929 PNGase was shown to be Man beta 1-->4GlcNAc beta 1-->4GlcNAc beta 1-->peptide, GlcNAc2 may be directly accessible to the catalytic site in competition with substrate. Interestingly, alkylation of -SH group in L-929 PNGase caused complete loss of the catalytic activity, but the carbohydrate binding activity was completely retained, indicating that the catalytic site(s) is discriminated from the carbohydrate-binding sites in the active site of this enzyme. The carbohydrate binding property seems to be unique to soluble PNGases from mammals and may be associated not only with regulation of the enzyme activity, but also with receptor and carrier functions for glycoconjugates in certain intracellular processes. PMID- 7797503 TI - Structure of human parathyroid hormone 1-37 in solution. AB - Human parathyroid hormone (hPTH), amino acids Ser1 to Leu37, is biologically active with respect to both receptor binding and activation of adenylate cyclase to influence the serum calcium concentration. It induces DNA synthesis via an unknown signal pathway. We investigated the structure of hPTH(1-37) in H2O/buffer solution under near physiological conditions, that is pH 6.0 and 270 mM salt, by circular dichroism, ultracentrifugation, nuclear magnetic resonance spectroscopy, and molecular dynamics calculations. Complete sequence specific assignments of all 1H resonances were performed by using 1H two-dimensional NMR measurements (double quantum-filtered correlated spectroscopy, nuclear Overhauser effect spectroscopy (NOESY), and total correlation spectroscopy with suppression of NOESY-type cross-peaks spectra). hPTH(1-37) obtained helical structure and showed hydrophobic interactions defining a tertiary structure. The NH2-terminal four amino acids of hPTH(1-37) did not show a stable conformation. Evidence for an alpha-helical region between Ile5 and Asn10 was found. This region was followed by a flexible link (Gly12, Lys13) and a well defined turn region, His14 to Ser17. The latter was stabilized by hydrophobic interactions between Trp23 and Leu15. Ser17 through at least Leu28 formed an alpha-helix. Arg20 and Lys27 were involved in the core built by His14 to Ser17. Unrestrained molecular dynamics simulations indicated that the structure was stable on the 200 ps time scale. PMID- 7797504 TI - Long-lasting changes of calcium oscillations in astrocytes. A new form of glutamate-mediated plasticity. AB - Long-term changes of synaptic strength in the central nervous system are mediated by an increase of cytosolic calcium concentration ([Ca2+]i) following activation of excitatory neurotransmitter receptors. These phenomena, which represent a possible cellular basis for learning and memory processes in eukaryotes, are believed to be restricted to neurons. Here we provide evidence for a long-term change of the response elicited by the excitatory neurotransmitter glutamate in a non-neuronal cell population of the central nervous system, i.e. visual cortical astrocytes in culture. Stimulation with glutamate induces in astrocytes a regular pattern of [Ca2+]i oscillations. A second stimulation, after an interval ranging from 2 to 60 min, induces an oscillatory response characterized by an increased frequency. Induction of this change in the astrocyte response is abolished by a specific inhibitor of the nitric oxide synthase and recovers upon exogenous nitric oxide generation or addition of a permeant cGMP analogue. Local brief pulses of glutamate to individual astrocytes, at a rate of 1 Hz, also elicit [Ca2+]i oscillations whose frequency increases following a second series of pulses. The long-lasting modification in the [Ca2+]i oscillatory response induced by glutamate in astrocytes demonstrates that in the central nervous system cellular memory is not a unique feature of neurons. PMID- 7797505 TI - Molecular cloning and expression of cDNA encoding the rat UDP-N acetylglucosamine:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II. AB - UDP-N-acetyl-D-glucosamine:alpha-6-D-mannoside beta-1,2-N acetylglucosaminyltransferase II (EC 2.4.1.143) (GnT II) is a Golgi resident enzyme that catalyzes an essential step in the biosynthetic pathway leading from high mannose to complex N-linked oligosaccharides. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the enzyme purified from rat liver revealed a polypeptide of 42 kDa. Amino acid sequences were obtained from the N terminus and a tryptic peptide. Overlapping cDNA clones coding for the full length rat GnT II were obtained. The complete nucleotide sequence revealed a 1326 base pair open reading frame that codes for a polypeptide of 442 amino acids, including a presumptive N-terminal membrane-anchoring domain. The region of cDNA coding for the C-terminal 389 amino acids of rat GnT II was linked in frame to a cDNA segment encoding the cleavable signal sequence of the human interleukin-2 receptor and transiently expressed in COS-7 cells. A 77-fold enhancement of GnT II activity over a control carrying the GnT II cDNA out-of-frame was detected in the culture medium at 72 h after transfection. 1H-NMR spectroscopy confirmed that the oligosaccharide synthesized in vitro by the recombinant enzyme was the product of GnT II activity. These data verify the identity of the cloned GnT II cDNA and demonstrate that the C-terminal region of the protein includes the catalytic domain. PMID- 7797507 TI - Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in FRTL-5 cells. I. Identification and characterization of a cyclic AMP-responsive element in the rat reductase promoter. AB - Thyrotropin (TSH) increases 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene transcription in FRTL-5 rat thyroid cells, and the effect of TSH can be mimicked by cAMP. Sequence analysis of the rat reductase promoter has revealed a hitherto unnoticed cAMP-responsive element (CRE)-like octamer. This octamer is located between 53 and 60 nucleotides downstream of the sterol regulatory element 1; its first 6 nucleotides are identical to the consensus somatostatin CRE, and the entire octamer is identical to the fos CRE. A synthetic oligonucleotide containing the HMG-CoA reductase CRE-like octamer (RED CRE) formed protein-DNA complexes with nuclear extracts from FRTL-5 cells, which could be prevented by unlabeled CRE-containing oligonucleotides whose flanking sequences were otherwise nonidentical. The complexes were specifically supershifted by anti-CREB antibodies. FRTL-5 cells transfected with a fusion plasmid carrying the bacterial chloramphenicol acetyl transferase (CAT) under the control of the HMG-CoA reductase promoter displayed CAT activity, which was specifically stimulated by TSH. In contrast, CAT activity in FRTL-5 cells transfected with similar constructs carrying mutations in the reductase CRE was significantly lower and did not increase after TSH challenge. We suggest that the HMG-CoA reductase gene contains a functional CRE, important for TSH regulation of transcription. The data presented provide the molecular basis for a novel regulatory mechanism for HMG-CoA reductase gene expression in rat thyroid cells, which involves the direct effect of cAMP. PMID- 7797506 TI - pH regulation of the F-actin binding properties of Dictyostelium elongation factor 1 alpha. AB - ABP50, an F-actin bundling protein from Dictyostelium, is also the protein synthesis co-factor, elongation factor 1 alpha (EF1 alpha). Concomitant with cAMP stimulation in Dictyostelium is a cytoplasmic alkalinization (Aerts, R. J., DeWit, R. J. W., and Van Lookeren Campagne, M. M. (1987) FEBS Lett. 220, 366-370) and a redistribution of EF1 alpha (Dharmawardhane, S., Demma, M., Yang, F., and Condeelis, J. (1991) Cell Motil. Cytoskel. 20, 279-288). In addition, others have shown a correlation between intracellular pH and the level of protein synthesis in Dictyostelium (Aerts, R. J., Durston, A. J., and Moolenaar, W. H. (1985) Cell 43, 653-657). The present study investigates the relationship between pH and the F-actin binding properties of EF1 alpha. We found that increasing pH over the physiological range 6.2-7.8 causes a loss of EF1 alpha-mediated F-actin bundling and single filament binding, with corresponding increases in the amount of free EF1 alpha in vitro. Similar results also were obtained by cell fractionation and confocal immunofluorescence microscopy. The EF1 alpha binding constant (Kd) for F actin is increased from 0.2 microM to > 2.2 microM over the same pH range. In addition, EF1 alpha-induced actin bundle formation is freely reversible by changes in pH. Thus, pH may be a potent modulator of cytoarchitecture in Dictyostelium and may also influence mRNA translation rates by modifying the interactions between the protein synthetic machinery and the actin cytoskeleton. PMID- 7797508 TI - Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in FRTL-5 cells. II. Down-regulation by v-K-ras oncogene. AB - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and mRNA levels were significantly reduced in FRTL-5 cells transformed with the Kirsten Moloney sarcoma virus (KiMol); these cells have lost thyrotropin dependence and express high levels of p21ras. FRTL-5 cells, transformed with a temperature sensitive mutant of the v-K-ras oncogene (Ats cells: 33 degrees C, permissive; 39 degrees C, nonpermissive), showed significant reduction of HMG-CoA reductase expression when exposed to 33 degrees C. In KiMol cells, as well as in Ats cells at 33 degrees C, the transcription driven by cAMP-responsive element was probed by measuring chloramphenicol acetyl transferase (CAT) levels after transfection with a chimeric plasmid containing the reporter gene linked to the rat reductase promoter. Basal CAT activity in KiMol cells transfected with wild-type promoter was lower than in FRTL-5 cells but was increased by forskolin to the levels attained in thyrotropin-stimulated FRTL-5 cells. Forskolin failed to increase CAT activity in KiMol cells transfected with the plasmid harboring a reductase promoter in which the cAMP-responsive element octamer was mutated to a nonpalindromic sequence. The effect of v-K-ras could be mimicked in FRTL-5 cells by tetradecanoyl phorbol acetate and reverted in KiMol and Ats cells, expressing active Ras protein, by increasing intracellular cAMP and/or by protein kinase C inhibition. The data are consistent with the contention that v-K-ras, through protein kinase C and depletion of intracellular cAMP, is inhibitory for the protein kinase A pathway. This is the first demonstration that active v-K-ras down-regulates HMG-CoA reductase expression. PMID- 7797510 TI - Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases. AB - Interleukin-1 beta converting enzyme (ICE) is a cytoplasmic cysteine protease required for generating the bioactive form of the interleukin-1 beta cytokine from its inactive precursor. We report the identification of ICH-2, a novel human gene encoding a member of the ICE cysteine protease family, and characterization of its protein product. ICH-2 mRNA is widely expressed in human tissues in a pattern similar to, but distinct from, that of ICE. Overexpression of ICH-2 in insect cells induces apoptosis. Purified ICH-2 is functional as a protease in vitro. A comparison of the inhibitor profiles and substrate cleavage by ICH-2 and ICE shows that the enzymes share catalytic properties but may differ in substrate specificities, suggesting that the two enzymes have different functions in vivo. PMID- 7797509 TI - Interaction of the microtubule cytoskeleton with endocytic vesicles and cytoplasmic dynein in cultured rat hepatocytes. AB - In a recent study (Goltz, J.S., Wolkoff, A.W., Novikoff, P.M., Stockert, R.J., and Satir, P. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7026-7030), we found that ligand- and receptor-containing endocytic vesicles bind to endogenous microtubules in vitro after 60 min of receptor-mediated endocytosis of asialo orosomucoid. In the presence of ATP, ligand-containing endocytic vesicles are released from microtubules, while those containing receptor are not. We hypothesized that cytoplasmic dynein may associate with ligand-containing, but not receptor-containing, domains of endocytic vesicles and might be involved in the movement of ligand-containing vesicles along microtubules during sorting of ligand from receptor. Direct evidence in support of this hypothesis has been obtained in the present study. Binding of ligand-containing vesicles to microtubules correlates highly (p < 0.001) with binding of dynein, but not kinesin, under a variety of conditions. Binding of receptor-containing vesicles to microtubules is independent of both cytoplasmic dynein and kinesin binding. Tight association of cytoplasmic dynein with a population of ligand-containing vesicles is seen directly by immunoprecipitation. These results support the view that in receptor-mediated endocytosis, ligand-containing vesicles become bound to microtubules by cytoplasmic dynein. While receptor domains of endosomes remain attached to microtubules in an ATP-independent manner, ligand-containing domains might be moved away toward pericentrosomal lysosomes by this motor molecule. PMID- 7797511 TI - Natural catalytic antibodies: peptide-hydrolyzing activities of Bence Jones proteins and VL fragment. AB - Monoclonal human light chains, i.e. Bence Jones proteins, and their recombinant variable fragments (VL) were screened for proteolytic activity using peptide methylcoumarinamide (peptide-MCA) conjugates and vasoactive intestinal polypeptide (VIP) as substrates. Sixteen of 21 Bence Jones proteins and one of three VL fragments were capable of detectable cleavage of one or more substrates. The magnitude and kinetic characteristics of the activity varied with different substrates. Among the peptide-MCA substrates, the presence of tripeptide or tetrapeptide moieties with a basic residue at the scissile bond generally favored expression of the activity. The influence of N-terminal flanking residue recognition was evident from differing values of Km and kcat (turnover number) observed using different Arg-containing peptide-MCA substrates. Different light chains displayed different kinetic parameters for the same substrate, suggesting unique catalytic sites. Hydrolysis of VIP was characterized by nanomolar Michaelis-Menten constants (Km), suggesting comparatively high affinity recognition of this peptide. The 25-kDa monomer and the 50-kDa dimer forms of one light chain preparation were resolved by gel filtration in 6 M guanidine hydrochloride. Following renaturation, the monomer displayed 51-fold greater peptide-MCA-hydrolyzing activity than the dimer. A renatured VL domain prepared by gel filtration in 6 M guanidine hydrochloride displayed VIP-hydrolyzing activity in the 12.5-kDa peak fractions. These results provide evidence for the proteolytic activity of certain human light chains and imply that this phenomenon may have a pathophysiological significance. PMID- 7797512 TI - Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. AB - Endothelins (ET) are a family of potent vasoactive peptides that are produced from biologically inactive intermediates, termed big endothelins, via a proteolytic processing at Trp21-Val/Ile22. We recently cloned and characterized a membrane-bound metalloprotease that catalyzes this proteolytic activation, endothelin-converting enzyme-1 (ECE-1) (Xu, D., Emoto, N., Giaid, A., Slaughter, C., Kaw, S., deWit, D., and Yanagisawa, M. (1994) Cell 78, 473-485). This enzyme was shown to function in the secretory pathway as well as on the cell surface. Here we report molecular cloning of another novel enzyme, ECE-2, that produces mature ET-1 from big ET-1 both in vitro and in transfected cells. The cDNA sequence predicts that bovine ECE-2 is a metalloprotease structurally related to ECE-1, neutral endopeptidase 24.11, and human Kell blood group protein. The deduced amino acid sequence of ECE-2 is most similar to ECE-1, with an overall identity of 59%. ECE-2 resembles ECE-1 in that it is inhibited in vitro by phosphoramidon and FR901533 but not by thiorphan or captopril, and it converts big ET-1 more efficiently than big ET-2 or big ET-3. However, ECE-2 also exhibits the following striking differences from ECE-1. (i) The sensitivity of ECE-2 to phosphoramidon is 250-fold higher as compared with ECE-1, while FR901533 inhibits both enzymes at similar concentrations. (ii) ECE-2 has an acidic pH optimum at pH 5.5, which is in sharp contrast to the neutral pH optimum of ECE-1. ECE-2 has a narrow pH profile and is virtually inactive at neutral pH. Chinese hamster ovary (CHO) cells, which lack detectable levels of endogenous ECE activity, secrete mature ET-1 into the medium when doubly transfected with ECE-2 and prepro-ET-1 cDNAs. However, ECE-2-transfected CHO cells do not efficiently produce mature ET 1 when present with an exogenous source of big ET-1 through coculture with prepro ET-1-transfected CHO cells. These findings suggest that ECE-2 acts as an intracellular enzyme responsible for the conversion of endogenously synthesized big ET-1 at the trans-Golgi network, where the vesicular fluid is acidified. PMID- 7797513 TI - Factors determining specificity of signal transduction by G-protein-coupled receptors. Regulation of signal transfer from receptor to G-protein. AB - Among subfamilies of G-protein-coupled receptors, agonists initiate several cell signaling events depending on the receptor subtype (R) and the type of G-protein (G) or effector molecule (E) expressed in a particular cell. Determinants of signaling specificity/efficiency may operate at the R-G interface, where events are influenced by cell architecture or accessory proteins found in the receptor's microenvironment. This issue was addressed by characterizing signal transfer from R to G following stable expression of the alpha 2A/D adrenergic receptor in two different membrane environments (NIH-3T3 fibroblasts and the pheochromocytoma cell line, PC-12). Receptor coupling to endogenous G-proteins in both cell types was eliminated by pertussis toxin pretreatment and R-G signal transfer restored by reconstitution of cell membranes with purified brain G-protein. Thus, the receptor has access to the same population of G-proteins in the two different environments. In this signal restoration assay, agonist-induced activation of G was 3-9-fold greater in PC-12 as compared with NIH-3T3 alpha 2-adrenergic receptor transfectants. The cell-specific differences in signal transfer were observed over a range of receptor densities or G-protein concentration. The augmented signal transfer in PC-12 versus NIH-3T3 transfectants occurred despite a 2-3-fold lower level of receptors existing in the R-G-coupled state (high affinity, guanyl-5'-yl imidodiphosphate-sensitive agonist binding), suggesting the existence of other membrane factors that influence the nucleotide binding behavior of G-protein in the two cell types. Detergent extraction of PC-12 but not NIH-3T3 membranes yielded a heat-sensitive, macromolecular entity that increased 35S-labeled guanosine 5'-O-(thiotriphosphate) binding to brain G protein in a concentration-dependent manner. These data indicate that the transfer of signal from R to G is regulated by a cell type-specific, membrane associated protein that enhances the agonist-induced activation of G. PMID- 7797515 TI - Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor alpha. AB - Ferritin is a ubiquitously distributed iron-binding protein that plays a key role in cellular iron homeostasis. It is composed of two subunits, termed H (heavy or heart) and L (light or liver). In fibroblasts and other cells, the cytokine tumor necrosis factor-alpha (TNF) specifically induces synthesis of the ferritin H subunit. Using nuclear run-off assays, we demonstrate that this TNF-dependent increase in ferritin H is mediated by a selective increase in ferritin H transcription. Transfection of murine fibroblasts with chimeric genes containing the 5'-flanking region of murine ferritin H fused to the human growth hormone reporter gene reveals that the cis-acting element that mediates this response is located approximately 4.8 kilobases distal to the start site of transcription. Deletion analyses delimit the TNF-responsive region to a 40-nucleotide sequence located between nucleotides -4776 and -4736, which we term FER-2. Electrophoretic mobility shift assays and site-specific mutations indicate that this region contains two independent elements: one contains a sequence that binds a member of the NF-kappa B family of transcription factors, and a second contains a novel sequence that partially conforms to the NF-kappa B consensus sequence and may bind a different member of the NF-kappa B/Rel transcription factor family. Thus, effects of an inflammatory cytokine on ferritin are mediated by a family of transcription factors responsive to oxidative stress. PMID- 7797514 TI - A constitutive heat shock element-binding factor is immunologically identical to the Ku autoantigen. AB - Analysis of the heat shock element (HSE)-binding proteins in extracts of rodent cells, during heat shock and their post-heat shock recovery, indicates that the regulation of heat shock response involves a constitutive HSE-binding factor (CHBF), in addition to the heat-inducible heat shock factor HSF1. We purified the CHBF to apparent homogeneity from HeLa cells using column chromatographic techniques including an HSE oligonucleotide affinity column. The purified CHBF consists of two polypeptides with apparent molecular masses of 70 and 86 kDa. Immunoblot and gel mobility shift analysis verify that CHBF is identical or closely related to the Ku autoantigen. The DNA binding characteristics of CHBF to double-stranded or single-stranded DNA are similar to that of Ku autoantigen. In gel mobility shift analysis using purified CHBF and recombinant human HSF1, CHBF competes with HSF1 for the binding of DNA sequences containing HSEs in vitro. Furthermore, when Rat-1 cells were co-transfected with human Ku expression vectors and the hsp70-promoter-driven luciferase reporter gene, thermal induction of luciferase is significantly suppressed relative to cells transfected with only the hsp70-luciferase construct. These data suggest a role of CHBF (or Ku protein) in the regulation of heat response in vivo. PMID- 7797516 TI - Rhodopsin kinase autophosphorylation. Characterization of site-specific mutations. AB - Upon illumination, rhodopsin kinase (RK) phosphorylates the visual pigment rhodopsin, which is thought to partially terminate the biochemical events that follow photon absorption. RK enzymology was explored by mutagenesis of the residues Ser488, Thr489 (major autophosphorylation sites), and Lys491 (a distal residue). We found the following to be true. (i) Double mutations at residues Ser488 and Thr489 to Ala or Asp decrease autophosphorylation to substoichiometrical levels, while single mutations at either residue independently reduce autophosphorylation by half. (ii) Phosphorylation of residue Ser488 influences the affinity of RK for heparin-Sepharose only moderately, whereas Thr489 and Lys491 are important for this interaction. RK K491A does not phosphorylate acidic peptides, suggesting that this residue participates in substrate binding. (iii) Mutations in the autophosphorylation region affect the Km for ATP, suggesting that this region is involved in binding of ATP to the catalytic site. (iv) RK mutants S488A or S488D and RK S488A and T489A have an increased ability to phosphorylate Rho in the dark. (v) Mutations at the autophosphorylation region change the initial site of phosphorylation on photolyzed rhodopsin (Rho*), implying that this region may regulate selectivity of the site of phosphorylation. PMID- 7797518 TI - A conserved domain and membrane targeting of Nef from HIV and SIV are required for association with a cellular serine kinase activity. AB - Among the primate lentiviruses (human immunodeficiency virus (HIV) -1, HIV-2, and simian immunodeficiency virus (SIV), the nef gene is highly conserved and encodes a myristylated protein of approximately 27 kDa (HIV-1) or approximately 34 kDa (HIV-2, SIV). Previously, we found Nef expressed either as a CD8-Nef fusion protein or as a native protein in virally infected T cell lines associates with a cellular serine kinase. This kinase activity phosphorylated two proteins of 62 and 72 kDa that coimmunoprecipitate with Nef in in vitro kinase assays. Using transient expression, various Nef alleles and mutants have been analyzed for association with the cellular kinase activity. The ability of Nef to associate with the kinase activity is conserved among several alleles of HIV-1 as well as SIVmac239 and is observed in non-lymphoid cell lines of simian and murine origins. Two separate regions of HIV-1SF2 Nef are critical for the associated kinase activity. One domain overlaps with a central highly conserved region found in all primate lentivirus nef genes and has been provisionally mapped to amino acids 45-127. Because membrane localization of Nef is important for the associated cellular kinase activity, the second domain represents a membrane targeting signal. Moreover, point mutations within the central region that abrogate the Nef-associated kinase activity in HIV-1SF2 Nef have the same effect when introduced into SIVmac239open Nef. PMID- 7797517 TI - Chloroplasts can accommodate inclusion bodies. Evidence from a mutant of Chlamydomonas reinhardtii defective in the assembly of the chloroplast ATP synthase. AB - We identified two neighboring missense mutations in the chloroplast atpA gene which are responsible for the defect of ATP synthase assembly in the FUD16 mutant from Chlamydomonas reinhardtii. The two corresponding amino acid substitutions, Ile184-->Asn and Asn186-->Tyr, occurred at strictly conserved sites among the alpha and beta subunits of (C)F1 complexes from bacteria, mitochondria, and chloroplasts. The altered region in the alpha polypeptide chain is located 7 amino acids downstream of the P-loop, which forms most of the conserved nucleotide binding site. Although the resulting chloroplast mutant fails to accumulate most of the ATP synthase subunits, it displays an increased intracellular content in both the alpha and beta subunits. We demonstrate that the two subunits do not bind to the thylakoid membranes but associate and overaccumulate in the chloroplast stroma as inclusion bodies. Increased rates of synthesis of the two subunits in the mutant point to an early interaction between the two subunits during their biogenesis. PMID- 7797519 TI - Catalytic activities of glycogenin additional to autocatalytic self glucosylation. AB - Glycogenin is the autocatalytic, self-glucosylating protein that initiates glycogen synthesis in muscle and other tissues. We have sequenced the cDNA for rabbit muscle glycogenin and expressed and purified the protein in high yield as well as two mutant proteins in which Phe or Thr replaces Tyr-194, the site of glucosylation. While the wild-type protein can self-glucosylate, the mutants cannot, but all three utilize alternative acceptors by intermolecular glucose transfer for which the mutants have altered specificity. Tyr-194 is therefore not essential for the catalytic activity of glycogenin. All three proteins also hydrolyze UDP-glucose to glucose at rates comparable with the rate of self glucosylation. The hydrolysis is competitive with glucose transfer to p nitrophenyl alpha-maltoside. Self-glucosylation, glucosylation of other acceptors, and hydrolysis all appear to be catalyzed by the same active center. In the absence of peptidase inhibitors, the homogenous recombinant proteins of M(r) 37,000 break down to equally active species having M(r) 32,000. The kinetics of self-glucosylation catalyzed by the wild-type enzyme suggest that the reaction could be intermolecular rather than, as previously reported, intramolecular. The wild-type recombinant enzyme and native muscle glycogenin, which is phosphorylated, are inhibited quite differently by ATP at physiological concentration. PMID- 7797520 TI - Purification and properties of wild-type and exonuclease-deficient DNA polymerase II from Escherichia coli. AB - Wild-type DNA polymerase II (pol II) and an exonuclease-deficient pol II mutant (D155A/E157A) have been overexpressed and purified in high yield from Escherichia coli. Wild-type pol II exhibits a high proofreading 3'-exonuclease to polymerase ratio, similar in magnitude to that observed for bacteriophage T4 DNA polymerase. While copying a 250-nucleotide region of the lacZ alpha gene, the fidelity of wild-type pol II is high, with error rates for single-base substitution and frameshift errors being < or = 10(-6). In contrast, the pol II exonuclease deficient mutant generated a variety of base substitution and single base frameshift errors, as well as deletions between both perfect and imperfect directly repeated sequences separated by a few to hundreds of nucleotides. Error rates for the pol II exonuclease-deficient mutant were from > or = 13- to > or = 240-fold higher than for wild-type pol II, depending on the type of error considered. These data suggest that from 90 to > 99% of base substitutions, frameshifts, and large deletions are efficiently proofread by the enzyme. The results of these experiments together with recent in vivo studies suggest an important role for pol II in the fidelity of DNA synthesis in cells. PMID- 7797521 TI - Potassium channel structure and function as reported by a single glycosylation sequon. AB - Inwardly rectifying K+ channels (IRKs) are highly K(+)-selective, integral membrane proteins that help maintain resting the membrane potential and cell volume. Integral membrane proteins as a class are frequently N-glycosylated with the attached carbohydrate being extracellular and perhaps modulating function. However, dynamic effects of glycosylation have yet to be demonstrated at the molecular level. ROMK1, a member of the IRK family is particularly suited to the study of glycosylation because it has a single N-glycosylation consensus sequence (Ho, K., Nichols, C. G., Lederer, W. J., Lytton, J., Vassilev, P. M., Kanazirska, M. V., and Herbert, S. C. (1993) Nature 362, 31-38). We show that ROMK1 is expressed in a functional state in the plasmalemma of an insect cell line (Spodoptera frugiperda, Sf9) and has two structures, glycosylated and unglycosylated. To test functionality, glycosylation was abolished by an N117Q mutation or by treatment with tunicamycin. Whole cell currents were greatly reduced in both of the unglycosylated forms compared to wild-type. Single channel currents revealed a dramatic decrease in opening probability, po, as the causative factor. Thus we have shown biochemically that the N-glycosylation sequon is extracellular, a result consistent with present topological models of IRKs, and we conclude that sequon occupancy by carbohydrate stabilizes the open state of ROMK1. PMID- 7797522 TI - The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R. AB - The Crk protein belongs to the family of proteins consisting of mainly Src homology 2 and 3 (SH2 and SH3) domains. These proteins are thought to transduce signals from tyrosine kinases to downstream effectors. In order to understand the specificity and effector function of the SH3 domain of Crk, we screened an expression library for binding proteins. We isolated Eps15, a substrate of the epidermal growth factor receptor (EGFR) tyrosine kinase, and Eps15R, a novel protein with high sequence homology to the carboxyl-terminal domain of Eps15. Antibodies raised against a fragment of the Eps15R gene product immunoprecipitated a protein of 145 kDa. Eps15 and Eps15R bound specifically to the amino-terminal SH3 domain of Crk and coprecipitated equivalently with both c Crk and v-Crk from cell lysates. The amino acid sequences of Eps15 and Eps15R featured several proline-rich regions as putative binding motifs for SH3 domains. In both Eps15 and Eps15R, we identified one proline-rich motif which accounts for their interaction with the Crk SH3 domain. Each binding motif contains the sequence P-X-L-P-X-K, an amino acid stretch that is highly conserved in all proteins known to interact specifically with the first SH3 domain of Crk. Furthermore, we found that immunoprecipitates of activated EGFR-kinase stably bound in vitro-translated Eps15 only in the presence of in vitro-translated v Crk. Crk might therefore be involved in Eps15-mediated signal transduction through the EGFR. PMID- 7797523 TI - A minimal motor domain from chicken skeletal muscle myosin. AB - The myosin head (S1) consists of a wide, globular region that contains the actin- and nucleotide-binding sites and an alpha-helical, extended region that is stabilized by the presence of two classes of light chains. The essential light chain abuts the globular domain, whereas the regulatory light chain lies near the head-rod junction of myosin. Removal of the essential light chain by a mild denaturant exposes the underlying heavy chain to proteolysis by chymotrypsin. The cleaved fragment, or "motor domain" (MD), migrates as a single band on SDS polyacrylamide gel electrophoresis, with a slightly greater mobility than S1 prepared by papain or chymotrypsin. Three-dimensional image analysis of actin filaments decorated with MD reveals a structure similar to S1, but shorter by an amount consistent with the absence of a light chain-binding domain. The actin activated MgATPase activity of MD is similar to that of S1 in Vmax and Km. But the ability of MD to move actin filaments in a motility assay is considerably reduced relative to S1. We conclude that the globular, active site region of the myosin head is a stable, independently folded domain with intrinsic motor activity, but the coupling efficiency between ATP hydrolysis and movement declines markedly as the light chain binding region is truncated. PMID- 7797524 TI - Complex interactions between yeast TFIIIB and TFIIIC. AB - Transcription of yeast class III genes requires the sequential assembly of the general transcription factors TFIIIC and TFIIIB, and of RNA polymerase III, into an initiation complex composed of at least 25 polypeptides. The 70-kDa subunit of TFIIIB (TFIIIB70) is central in this network of interactions as it contacts both TATA-binding protein and a subunit of polymerase III. We show here that the TATA binding protein interacts with the carboxyl-terminal part of TFIIIB70. TFIIIB70 also contacts TFIIIC (factor tau) via its tau 131 subunit. The protein domains of tau 131 and TFIIIB70 involved in this interaction, either positively or negatively, were mapped using the two-hybrid system. We provide evidence that intramolecular interactions mask functional domains in both polypeptides. PMID- 7797526 TI - Two Drosophila genes that encode the alph and beta subunits of the brain soluble guanylyl cyclase. AB - We identified two Drosophila genes (dgc alpha 1 and dgc beta 1) that encode the soluble guanylyl cyclase alpha and beta subunits, respectively. The putative Dgc alpha 1 protein is 76 kDa, has 35% amino acid identity with previously isolated alpha subunits, and was immunolocalized to the adult retina, to the optic lobes, and throughout the brain neuropil. The Dgc beta 1 protein is 86 kDa and exhibits 59% amino acid identity with the rat beta 1 protein. However, the Dgc beta 1 protein has an additional 118 amino acids inserted near the amino terminus, which makes it significantly larger than the rat beta 1. The Dgc beta 1 protein was immunolocalized to the optic lobes and throughout the brain neuropil, with no detectable expression in the retina. The Dgc alpha 1 and Dgc beta 1 cDNAs were stably transfected into human kidney 293 cells. Expression of the individual subunits and mixing of the individually expressed subunits failed to generate significant guanylyl cyclase activity. Only coexpression of the subunits resulted in significant guanylyl cyclase activity. Our results indicate that Dgc alpha 1 and Dgc beta 1 are soluble guanylyl cyclase alpha and beta subunits that are capable of forming a functional guanylyl cyclase heterodimer. PMID- 7797525 TI - Translocation of the 85-kDa phospholipase A2 from cytosol to the nuclear envelope in rat basophilic leukemia cells stimulated with calcium ionophore or IgE/antigen. AB - The rat mast cell line RBL-2H3.1 contains an 85-kDa cytosolic phospholipase A2 (cPLA2) that is very likely involved in liberating arachidonate from membrane phospholipid for the synthesis of eicosanoids following stimulation with either calcium ionophore or IgE/antigen. In this study, the intracellular location of cPLA2 was determined using immunofluorescence microscopy and immuno-gold electron microscopy. In nonstimulated cells, cPLA2 is distributed throughout the cytosol and is excluded from the nucleoplasm. Following cell activation with calcium ionophore, most of the cPLA2 translocates to the nuclear envelope, and the enzyme remains there during the entire period that ionophore is present. With IgE/antigen stimulation for 5 min, approximately 20-30% of the cPLA2 translocates to the nuclear envelope, and after 30 min of stimulation, most of the enzyme returns to the cytosol. Measurement of intracellular calcium using the dye Fura 2/AM shows that the level of calcium rises immediately after antigen is added, remains high for about 30 s, and then declines back to resting levels. Activation with calcium ionophore produces a 10-fold larger release of arachidonate than does stimulation with IgE/antigen. Thus, the results suggest that the extent of membrane binding of cPLA2 correlates with the release of arachidonate and that the site of arachidonate liberation is the nuclear envelope where many of the enzymes that oxygenate this fatty acid are located. PMID- 7797527 TI - T antigens encoded by replication-defective simian virus 40 mutants dl1135 and 5080. AB - We present a preliminary biochemical characterization of two simian virus 40 mutants that affect different T antigen replication functions. SV40 T antigen mutants dl1135 (delta 17-27 amino acids) and 5080 (P-L) have been studied extensively with regard to their ability to transform cells in culture and induce tumors in transgenic mice. Both mutants are defective for viral DNA replication in vivo. In order to assess in more detail the molecular basis for the in vivo replication defects of 5080 and dl1135, we expressed the mutant proteins using the baculovirus system and purified them by immunoaffinity chromatography. With each of the purified proteins, we examined some of the biochemical activities of T antigen required for replication, viz. ATPase, binding to the origin of replication (ori) and assembly on ori, DNA helicase and unwinding, and replication in in vitro assays. Consistent with previous studies, we found that the 5080 protein is defective for multiple biochemical activities including ATPase, helicase, ori-specific unwinding, and ATP-induced hexamerization. However, this mutant retains some sequence-specific DNA binding activity. In contrast, the dl1135 protein exhibited significant levels of activity in all assays, including the ability to drive SV40 DNA replication in vitro. Thus, dl1135 is one of several mutants with an altered amino-terminal domain which can replicate DNA in vitro, but not in vivo. Thus, while the 5080 mutation affects a T antigen enzymatic function directly required for viral DNA synthesis, dl1135 may alter an activity required to prepare the cell for viral replication. PMID- 7797528 TI - Differentiation of embryonal carcinoma cells to a neural or cardiomyocyte lineage is associated with selective expression of endothelin receptors. AB - Endothelins (ETs) were initially characterized as potent vasoactive peptides acting through at least two distinct receptors, ETA and ETB. Subsequently, their significant growth- and hypertrophy-promoting properties in cardiac and other cells were recognized. We investigated the expression of endothelin receptors during differentiation of a pluripotential embryonal carcinoma cell line (P19) to a cardiomyocyte or a neural lineage. These cells resemble those of the inner cell mass of the blastocyst, and their differentiation is believed to closely mimic critical events in early embryogenesis. Differentiation of P19 to a cardiomyocyte lineage, by aggregation and exposure to dimethyl sulfoxide resulted in induction of ETA receptors as demonstrated by radioligand binding studies, Northern blotting, and reporter gene analysis. Moreover, the P19 differentiated to a cardiac lineage responded to ET-1 with a 3-fold increase in the secretion of atrial natriuretic peptide. In contrast, differentiation to a neural lineage, by aggregation and exposure to retinoic acid, was associated with the induction of predominantly ETB. Therefore, selective differentiation of the P19 led to the differential expression of endothelin receptors in a pattern consistent with that observed in normal myocardial and neural tissue. The induction of endothelin receptors in a model system of early embryogenesis provides strong support for the critical role of this peptide/receptor family in differentiation and development. As well, this model system is well suited for the study of the mechanisms controlling endothelin receptor expression during differentiation. PMID- 7797529 TI - Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements. AB - Prohormone convertases are involved in the tissue-specific endoproteolytic processing of prohormones and neuropeptide precursors within the secretory pathway. In the present study, we have isolated genomic clones comprising the 5' terminal region of the human prohormone convertase 1 (PC1) gene and identified and characterized the PC1 promoter region. We found multiple transcription start sites located within a 15-base pair region, 205 base pairs upstream of the translation start codon. The promoter region is not G+C-rich and does not contain a canonical TATA box nor a CAAT box. Transient expression assays with a set of human PC1 gene fragments containing progressive 5' deletions demonstrate that the proximal promoter region is capable of directing high levels of neuroendocrine specific expression of reporter gene constructs. In addition, the proximal promoter region confers both basal and hormone-regulated promoter activity. Site specific mutagenesis experiments demonstrate that two closely spaced cAMP response elements within the proximal promoter region direct cAMP-mediated hormonal regulation of transcription of the PC1 gene. PMID- 7797530 TI - Addition of an endoplasmic reticulum retention/retrieval signal does not block maturation of enzymatically active peptidylglycine alpha-amidating monooxygenase. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal alpha-amidation of neural and endocrine peptides via a two-step reaction carried out in sequence by the monooxygenase and lyase domains contained in this bifunctional protein. Peptide alpha-amidation is thought to take place primarily in the secretory granules in which mature bioactive peptides are stored, and it is not known where in the secretory compartment newly synthesized PAM protein becomes enzymatically active. To address this question, PAM-3, a soluble bifunctional protein, was modified by addition of the KDEL endoplasmic reticulum (ER) retention/retrieval signal to its COOH terminus. PAM-3-KDEL protein stably expressed in hEK-293 cells or in AtT-20 cells was efficiently retained in the ER based on immunocytochemistry, pulse-chase experiments, and maintained endoglycosidase H sensitivity. The effect of the KDEL sequence was specific since PAM-3 with an inactive ER retention/retrieval signal (PAM-3-KDEV) moved through the secretory pathway like wild type PAM-3. In AtT-20 cells, PAM-3-KDEL was not subjected to the COOH-terminal endoproteolytic cleavage that generates a 75-kDa PAM protein from PAM-3 and PAM-3-KDEV. PAM-3-KDEL protein exhibited both monooxygenase and lyase activities with specific activities similar to those of the wild type PAM-3 and PAM-3-KDEV proteins. Thus, although PAM catalyzes a reaction that occurs primarily in the secretory granules, newly synthesized PAM protein becomes enzymatically competent in the ER. PMID- 7797531 TI - Purification of cranin, a laminin binding membrane protein. Identity with dystroglycan and reassessment of its carbohydrate moieties. AB - Cranin was described in 1987 as a membrane glycoprotein expressed in brain and many other tissues, which binds laminin with high affinity in a calcium-dependent manner. Dystrophin-associated glycoprotein ("dystroglycan") is a laminin-binding protein cloned in 1992 whose relation to cranin has remained uncertain. Here we describe the purification of cranin to homogeneity from sheep brain, show cranin to be a form of dystroglycan, and localize the N terminus of beta-dystroglycan to amino acid residue 654. We find that brain alpha-dystroglycan is tightly associated with membranes, and localizes to regions of synaptic contact as assessed by immunocytochemistry of rat cerebellum. Brain alpha-dystroglycan expresses high mannose/hybrid N-linked saccharides, terminal GalNAc residues, and the HNK-1 epitope. Although dystroglycan has previously been presumed to be a proteoglycan, the amino acid sequence, pI, O-sialoglycoprotease susceptibility, lectin-binding profile, and laminin-binding properties of brain dystroglycan are more typical of mucin-like proteins. Furthermore, using CHO mutant cell lines deficient in xylosyltransferase and galactosyltransferase I, which are required for glycosaminoglycan biosynthesis, it is shown that chondroitin sulfate and heparan sulfate are not critical for laminin binding, and indeed are apparently not expressed at all in dystroglycan from CHO cells. PMID- 7797533 TI - Intracellular cholesterol transport and compartmentation. PMID- 7797534 TI - The human apolipoprotein E gene is negatively regulated in human liver HepG2 cells by the transcription factor BEF-1. AB - Apolipoprotein E (apoE) is a major constituent of plasma lipoprotein that functions in lipid transport and redistribution (reverse cholesterol transport) and probably plays an important role in inhibiting the development and/or progression of atherosclerosis. While cis-acting regions involved in basal and tissue-specific control of the apoE gene have been identified by promoter mapping studies, much less is known about factors that regulate the gene. In this study, we demonstrate that the region between -94 and -84 upstream of transcriptional start site of the human apoE gene contains a binding site for the transcriptional repressor factor BEF-1, a tyrosine-phosphorylated nuclear protein that was first identified in HeLa cells. Using gel retardation assays, we show that HeLa cell derived BEF-1 binds the apoE BEF-1 homology, and this binding can be competed with the prototype BEF-1 sequence, but not by a mutated sequence. Furthermore, we demonstrate that the apoE- producing human liver HepG2 cell produces significant levels of BEF-1, which could bind to both the prototype BEF-1 sequence and the apoE homology, and be competed equivalently with cold BEF-1 or apoE homology. To determine if BEF-1 affected the expression of apoE, we performed competition experiments using plasmids containing the intact or mutated BEF-1 homology. The introduction of the intact BEF-1 site into HepG2 cells resulted in an induction of apoE mRNA, whereas control and mutated BEF-1-containing plasmids had no significant effect. We also found that increasing the level of nuclear BEF-1 by treatment of cells with orthovanadate resulted in a reduction in the level of apoE mRNA. Overall, our data suggest that the endogenous apoE gene in the human HepG2 cell line is repressed by the trans-acting influence of nuclear factor BEF 1. PMID- 7797532 TI - CuZn superoxide dismutase (SOD-1):tetanus toxin fragment C hybrid protein for targeted delivery of SOD-1 to neuronal cells. AB - Increased levels of CuZn superoxide dismutase (SOD-1) are cytoprotective in experimental models of neurological disorders associated with free radical toxicity (e.g. stroke, trauma). Targeted delivery of SOD-1 to central nervous system neurons may therefore be therapeutic in such diseases. The nontoxic C fragment of tetanus toxin (TTC) possesses the nerve cell binding/transport properties of tetanus holotoxin and has been used as a vector to enhance the neuronal uptake of proteins including enzymes. We have now produced a recombinant, hybrid protein in Escherichia coli tandemly joining human SOD-1 to TTC. The expressed hybrid protein (SOD:Tet450) has a subunit molecular mass of 68 kDa and is recognized by both anti-SOD-1 and anti-TTC antibodies. Calculated per mol, SOD:Tet450 has approximately 60% of the expected SOD-1 enzymatic activity. Analysis of the hybrid protein's interaction with the neuron-like cell line, N18 RE-105, and cultured hippocampal neurons by enzyme immunoassay for human SOD-1 revealed that SOD:Tet451 association with cells was neuron-specific and dose dependent. The hybrid protein was also internalized, but there was substantial loss of internalized hybrid protein over the first 24 h. Hybrid protein associated with cells remained enzymatically active. These results suggest that human SOD-1 and TTC retain their respective functional properties when expressed together as a single peptide. SOD:Tet451 may prove to be a useful agent for the targeted delivery of SOD-1 to neurons. PMID- 7797535 TI - Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. AB - We have identified a G-protein-coupled receptor specifically activated by parathyroid hormone, which we refer to as the PTH2 receptor. Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP, hypercalcemia of malignancy factor) activate a previously identified PTH/PTHrP receptor, which has a widespread tissue distribution. The PTH2 receptor is much more selective in ligand recognition and appears to have a more specific tissue distribution. It is activated by PTH and not by PTHrP and is particularly abundant in the brain and pancreas. PMID- 7797537 TI - Expression of human RAD52 confers resistance to ionizing radiation in mammalian cells. AB - Processing of mutagenic DNA damages by the double strand breaks (DSB) in eukaryotes is most likely achieved by multiple pathways, including homologous recombination. Although RAD52 has been shown to be important for DSB repair in yeasts, its role in DSB repair in mammalian cells has not been demonstrated. This study reports for the first time that the overexpression of human RAD52 confers enhanced resistance to gamma-rays and induces homologous intrachromosomal recombination in cultured monkey cells. Recombination frequency synergistically increased by the combination of overexpression of RAD52 and ionizing radiation. These observations suggest that homologous recombination mediated by RAD52 is involved in double-stranded break repair in mammalian cells. PMID- 7797538 TI - A two-step model for lipoprotein(a) formation. AB - Lipoprotein(a) (Lp(a)), a risk factor for coronary artery disease, is a LDL-like particle with apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B (apoB), the main protein component of LDL. Apo(a) is highly homologous to plasminogen and its gene probably arose by duplication of the plasminogen gene. It has many repeats of kringle-4-like domain, classified as type 1 through type 10 (T1-T10). T9 is responsible for the covalent linkage between apo(a) and LDL. However, we found that T9 has no affinity for LDL. Therefore, an initial noncovalent interaction between apo(a) and LDL is necessary to bring T9 and LDL together. T6 and possibly T7 of apo(a) were identified as the kringles which mediate this initial interaction. With these findings, a two-step model for Lp(a) formation is proposed. This model should be useful in the design of Lp(a) formation inhibitors. These inhibitors are potential antihyperlipoprotein(a) drugs. PMID- 7797536 TI - Role of heterogeneous N-terminal acylation of recoverin in rhodopsin phosphorylation. AB - Recoverin, a new member of the EF-hand superfamily, plays a critical role in the light/dark adaptation of retinal rods by regulating rhodopsin phosphorylation in a Ca(2+)-dependent manner. Recoverin is composed of four isoforms, each of which is modified at its N terminus by myristate (C14:0) or its structurally related fatty acid (C12:0, C14:2, or C14:1). Although the N-fatty acylation is implicated in protein-membrane and protein-protein interactions, the functional difference among the recoverin isoforms and the significance of the heterogeneous acylation have not been defined. Here we separated the heterogeneous recoverin into three fractions, C14:0-recoverin, C14:1-recoverin, and a mixture of C14:2- and C12:0- (C14:2/C12:0-) recoverin to evaluate the individual properties. Recoverin in every fraction bound Ca2+ as assessed by fluorescence spectroscopy and inhibited the light-dependent rhodopsin phosphorylation in the same range of free Ca2+ concentration (0.3-0.8 microM). However, the magnitude of the inhibition at higher Ca2+ concentration was different among the isoforms and ranked in the same order of the hydrophobicity of the N-fatty acyl groups: C14:0 > C14:1 > C14:2/C12:0. These results indicate that the diverged hydrophobicity of the recoverin N terminus plays an important role in the interaction with the membranes and/or its target protein but not with Ca2+. PMID- 7797539 TI - Reversible phosphorylation of both Tyr7 and Tyr10 in the alpha-chain of pig stomach H+,K(+)-ATPase by a membrane-bound kinase and a phosphatase. AB - When pig stomach membrane H+,K(+)-ATPase preparations were incubated with [gamma 32P]ATP and Mg2+ with vanadate, 32P was incorporated into the alpha-chain of H+,K(+)-ATPase to a steady-state level of approximately 0.7 mol of phosphotyrosine (Tyr(P))/mol of phosphoenzyme intermediates. The addition of a membrane H+,K(+)-ATPase preparation with Mg2+ accelerated the liberation of 32P from Tyr(P) residues in the alpha-chain. Mild tosylphenylalanyl chloromethyl ketone-trypsin treatment solubilized 32P-containing peptides from the alpha-chain almost completely. A reverse-phase column chromatography of the supernatant gave two peaks of 32P-peptide with similar total radioactivities. The amino acid sequence of both peaks was shown to be Gly-Lys-Ala-Glu-Asn-Tyr-Glu-Leu-Tyr-Gln--, which is consistent with the amino-terminal sequence of the alpha-chain of H+,K(+)-ATPase deduced from cDNA from pig stomach except that the initial Met was absent. The comparison of the recovery of amino acid from each Edman cycle showed that the phosphorylation of Tyr10 occurred preceding the phosphorylation of Tyr7. These data and others suggested the presence of a novel membrane-bound enzyme system to participate in reversible phosphorylation of both Tyr residues in the alpha-chain of H+,K(+)-ATPase. PMID- 7797540 TI - Calf thymus Hsc70 protein protects and reactivates prokaryotic and eukaryotic enzymes. AB - The heat-shock 70 protein (Hsp70) chaperone family is very conserved and its prokaryotic homologue, the DnaK protein, is assumed to form one of the cellular systems for the prevention and restoration of heat-induced protein denaturation. By using anti-DnaK antibodies we purified the DnaK homologue heat-shock cognate protein (Hsc70) from calf thymus to apparent homogeneity. This protein was classified as an eukaryotic Hsc70, since (i) monoclonal antibodies against eukaryotic Hsc70 recognized it, (ii) its amino-terminal sequence showed strong homology to Hsp70s from eukaryotes and, (iii) it had an intrinsic weak ATPase activity that was stimulated by various peptide substrates. We show that this calf thymus Hsc70 protein protected calf thymus DNA polymerases alpha and epsilon as well as Escherichia coli DNA polymerase III and RNA polymerase from heat inactivation and could reactivate these heat-inactivated enzymes in an ATP hydrolysis dependent manner, likely leading to the dissociation of aggregates formed during heat inactivation. In contrast to this, DnaK protein was exclusively able to protect and to reactivate the enzymes from E.coli but not from eukaryotic cells. Finally, the addition of calf thymus DnaJ co-chaperone homologue reduced the amount of Hsc70 required for reactivation at least 10-fold. PMID- 7797541 TI - Porcine m2 muscarinic acetylcholine receptor-effector coupling in Chinese hamster ovary cells. AB - The relationship between porcine m2 muscarinic receptor coupling to inhibition of cAMP formation and stimulation of phosphatidylinositol metabolism in Chinese hamster ovary cells was examined. Reduction of the number of receptors per cell with the slowly dissociating antagonist (-)-quinuclidinyl benzilate caused a decrease in maximal response with no effect on EC50 for coupling to phosphatidylinositol metabolism. Inhibition of cAMP formation showed the opposite dependence with no effect on maximal response but an increase in EC50 value as receptor density decreased. Pilocarpine appeared to be a partial agonist at low cell receptor density but displayed full agonism at higher receptor density. These results are compatible with a two-state model describing m2 muscarinic receptor acting via two different G proteins. This model is compatible with observations of negative antagonism where antagonists stimulated cAMP formation in adenylyl cyclase inhibition assays, and can also be used to estimate receptor affinities for G proteins in systems which display negative antagonism. PMID- 7797542 TI - Inhibition and labeling of the coated vesicle V-ATPase by 2-azido-[32P]ATP. AB - Previous studies have indicated that the 73-kDa A subunit of the coated vesicle V ATPase possesses a nucleotide-binding site essential for activity (Arai, H., Berne, M., Terres, G., Terres, H., Puopolo, K., and Forgac, M. (1987) Biochemistry 26, 6632-6638) and have identified a cysteine residue (Cys254) whose modification leads to complete loss of activity (Feng, Y., and Forgac, M. (1992) J. Biol. Chem. 267, 5817-5822). To further characterize the structure of the nucleotide-binding sites of the V-ATPase, labeling studies using the photoactivated analog 2-azido-[32P]ATP have been carried out. We have observed that 2-azido-[32P]ATP is hydrolyzed by the V-ATPase at a rate (at 1 mM) approximately 4-fold lower than observed for ATP, indicating that 2-azido [32P]ATP is a good substrate for the V-ATPase. Irradiation of the V-ATPase in the presence of 0.5 mM 2-azido-[32P]ATP leads to inactivation of V-ATPase activity with a t1/2 of 3-5 min. The 73-kDa A subunit, the 58-kDa B subunit, and the 50 kDa subunit of the AP-2 adaptin complex (Myers, M., and Forgac, M. (1993) J. Biol. Chem. 268, 9184-9186) are all labeled in an ATP-protectable manner on irradiation of the purified V-ATPase with 2-azido-[32P]ATP. The time course for inactivation most closely correlates with labeling of the A subunit. Measurement of the stoichiometry of 2-azido-[32P]ATP incorporation into the A subunit as a function of inactivation indicates that complete loss of activity is obtained on incorporation of 1.2 mol of 2-azido-[32P]ATP/mol V-ATPase complex. 2-Azido [32P]ATP labeling indicates that the V-ATPase possesses both rapidly (t1/2 < 2 min) and slowly (t1/2 > 2 min) exchangeable nucleotide-binding sites. The A subunit is labeled upon modification of both rapidly and slowly exchangeable sites whereas the B subunit is labeled upon modification of only rapidly exchangeable sites. Inhibition of V-ATPase activity correlates with labeling of the rapidly exchangeable sites. Amino acid sequence analysis of peptides derived from the 2-azido-[32P]ATP-labeled A subunit indicates labeling of two peptides: a 12-kDa fragment which begins at residue 511 and contains Cys532 and a 3-kDa fragment which begins at residue 233 and contains the glycine-rich loop and Cys254. Only the 12-kDa fragment is labeled upon modification of the rapidly exchangeable sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7797545 TI - Purification of the spliceosome A-complex and its visualization by electron microscopy. AB - Pre-mRNA splicing occurs on spliceosomes, a family of ribonucleoprotein particles. Spliceosome assembly on exogenous adenovirus pre-mRNA was blocked at the A-complex (or pre-spliceosome) stage, either by destruction of the small nuclear ribonucleoproteins (snRNPs) that comprise the U4/U5/U6 tri-snRNP complex, or by interference in tri-snRNP assembly and interactions. The A-complex was isolated by size exclusion chromatography; homogeneity was shown by electrophoresis in nondenaturing polyacrylamide gels, gradient sedimentation, and electron microscopy. Northern hybridization showed U1 and U2 snRNAs to be present in the preparation, but not U4, U5, or U6. Antibodies specific for a component of the U1 snRNP or for a component that is common to all snRNPs (except U6) each precipitated an A-complex containing pre-mRNA, U1 and U2 snRNPs. Electron micrographs showed 230 x 270-A particles whose two components appear similar to individual U1 and U2 snRNPs. Electron micrographs of an A-complex-5'-biotinyl oligonucleotide-streptavidin-gold composite allowed identification of the U2 snRNP within the structure and the localization of the 5'-segment of U2 snRNA at a unique site in the A-complex. This region of U2 RNA is adjacent to the developing catalytic center of the spliceosome. PMID- 7797544 TI - Calcium-induced troponin flexibility revealed by distance distribution measurements between engineered sites. AB - The contraction of vertebrate striated muscle is regulated by Ca2+ binding to troponin C (TnC). This causes conformational changes which alter the interaction of TnC with the inhibitory protein TnI and the tropomyosin-binding protein TnT. We have used the frequency domain method of fluorescence resonance energy transfer to measure TnT-TnC and TnT-TnI distances and distance distributions, in the presence of Ca2+, Mg2+, or EGTA, in TnC.TnI.TnT complexes. We reconstituted functional, ternary troponin complexes using the following recombinant subunits whose sequences were based on those of rabbit skeletal muscle: wild-type TnC; TnT25, a mutant C-terminal 25-kDa fragment of TnT containing a single Trp212 which was used as the sole donor for fluorescence energy transfer measurements; Trp-less TnI mutants which contained either no Cys or a single Cys at position 9, 96, or 117. Energy acceptor groups were introduced into TnC or TnI by labeling with dansyl aziridine or N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine. Our results indicate that the troponin complex is relatively rigid in relaxed muscle, but becomes much more flexible when Ca2+ binds to regulatory sites in TnC. This increased flexibility may be propagated to the whole thin filament, releasing the inhibition of actomyosin ATPase activity and allowing the muscle to contract. This is the first report of distance distribution measurements between troponin subunits. PMID- 7797543 TI - Phosphatidylinositol 3-kinase, but not p70/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin. Dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression. AB - Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP) and glucocorticoids stimulate the transcription of the PEPCK gene, whereas insulin and phorbol esters inhibit, in a dominant fashion, these effects. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, prevents the stimulation of glycogen synthesis, glucose transport, mitogen-activated protein kinase, and p70/p85 ribosomal S6 protein kinase by insulin. We now show that wortmannin can also block the inhibition of glucocorticoid- and cAMP-stimulated PEPCK gene expression by insulin. PEPCK-chloramphenicol acetyltransferase fusion gene experiments demonstrate that wortmannin blocks an activity that is required for insulin signaling to elements within the PEPCK promoter. Phorbol esters mimic the action of insulin on the regulation of PEPCK gene expression, but wortmannin does not block the effect of these agents. Thus, phosphatidylinositol 3-kinase is required for the regulation of PEPCK gene expression by insulin, but not by phorbol esters. The immunosuppressant rapamycin, a potent inhibitor of insulin or phorbol ester stimulation of p70/p85 ribosomal S6 protein kinase, has no significant effect on the regulation of PEPCK gene expression by insulin or phorbol esters. Thus, p70/p85 ribosomal S6 protein kinase does not have a role in signaling to the PEPCK promoter by insulin or phorbol esters. PMID- 7797546 TI - High affinity Ca(2+)-binding site in the serine protease domain of human factor VIIa and its role in tissue factor binding and development of catalytic activity. AB - Factor VIIa, in the presence of Ca2+ and tissue factor (TF), initiates the extrinsic pathway of blood coagulation. The light chain (amino acids 1-152) of factor VIIa consists of an N-terminal gamma-carboxyglutamic acid (Gla) domain followed by two epidermal growth factor-like domains, whereas the heavy chain (amino acids 153-406) contains the serine protease domain. In this study, both recombinant factor VIIa (rVIIa) and factor VIIa lacking the Gla domain were found to contain two high-affinity (Kd approximately 150 microM) Ca2+ binding sites. The rVIIa also contained approximately 6-7 low-affinity (Kd approximately 1 mM) Ca(2+)-binding sites. By analogy to other serine proteases, one of the two high affinity Ca(2+)-binding sites in factor VIIa may be formed involving Glu-210 and Glu-220 of the protease domain. In support of this, a synthetic peptide composed of residues 206-242 of factor VIIa bound one Ca2+ with Kd approximately 230 microM; however, Ca2+ binding was observed only in Tris buffer (pH 7.5) containing 1 M NaCl and not in buffer containing 0.1 M NaCl. In both low or high salt +/- Ca2+, the peptide existed as a monomer as determined by sedimentation equilibrium measurements and had no detectable secondary structure as determined by CD measurements. This indicates that subtle changes undetectable by CD may occur in the conformation of the peptide that favor calcium binding in high salt. In the presence of recombinant TF and 5 mM Ca2+, the peptide inhibited the amidolytic activity of rVIIa toward the synthetic substrate, S-2288. The concentration of the peptide required for half-maximal inhibition was approximately 5-fold higher in the low salt buffer than that in the high salt buffer. From direct binding and competitive inhibition assays of active site blocked 125I-rVIIa binding to TF, the Kd for peptide-TF interaction was calculated to be approximately 15 microM in the high salt and approximately 55 microM in the low salt buffer containing 5 mM Ca2+. Moreover, as inferred from S 2288 hydrolysis, the Kd for VIIa.TF interaction was approximately 1.5 microM in the absence of Ca2+, and, as inferred from factor X activation studies, it was approximately 10 pM in the presence of Ca2+. Thus, Ca2+ decreases the functional Kd of VIIa.TF interaction approximately 150,000-fold.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7797548 TI - Identification of an essential second metal ion in the reaction mechanism of Escherichia coli adenylosuccinate synthetase. AB - This study reports that two Mg2+ ions are required for Escherichia coli adenylosuccinate synthetase activity. The first metal ion is presumably coordinated with beta- and gamma-phosphoryl groups of GTP to provide an electron sink, and the second one seems to interact with aspartate in the enzyme active site. Regarding the latter metal ion, kinetic studies show that aspartate and the second Mg2+ ion bind to the enzyme active site randomly with a kcat value of 1.47 s-1 and with Km values for aspartate and Mg2+ of 225 and 114 microM, respectively. The dissociation constants for aspartate and Mg2+ of the enzyme.GTP.IMP.(aspartate or Mg2+) complex are 79.2 and 40.0 microM, respectively. However, variable amounts of aspartate or Mg2+ did not show any significant changes in the Km values for GTP and IMP. Kinetic studies using Mn2+ and Ca2+ ions indicate that the kcat values (0.930 and 0.235 s-1, respectively) were slightly decreased compared with the value obtained using Mg2+; however, the Km values for aspartate and GTP in the presence of Mn2+ and Ca2+ were significantly decreased compared with those obtained using Mg2+ ion (4.5 and 4.6 times for Mn2+ ion and 5.6 and 5.8 times for Ca2+ ion, respectively). On the other hand, the Km values for IMP were not significantly changed (1.9 and 1.8 times for Mn2+ and Ca2+ ions, respectively). Taken together, these kinetic results imply that aspartate may interact with Mg2+ to form a Mg.aspartate complex in the enzyme active site. An inhibition study of the enzyme with ZnCl2 (its Ki value is 29 nM) also suggested that Zn2+ competes with aspartate as well as Mg2+, implying that Zn2+ might form a complex with aspartate in the active site. On the basis of these results, it is suggested that Mg.aspartate complex formation in the active site of adenylosuccinate synthetase may be important in activation of the protonated amino group of aspartate, enhancement of the enzyme's binding affinity, and its specificity for aspartate. PMID- 7797547 TI - Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and beta ketoacyl-acyl carrier protein synthases in Escherichia coli. AB - The cessation of phospholipid biosynthesis by the inhibition of the sn-glycerol-3 phosphate acyltransferase using a plsB mutant led to an accumulation of long chain acyl-acyl carrier proteins (acyl-ACP) and the concomitant inhibition of de novo fatty acid biosynthesis in Escherichia coli. Malonyl-CoA did not accumulate when phospholipid and fatty acid synthesis was blocked. However, the inactivation of beta-ketoacyl-ACP synthases I and II with the antibiotic cerulenin triggered a large increase in the accumulation of malonyl-CoA following the cessation of phospholipid synthesis, illustrating that the beta-ketoacyl-ACP synthases were responsible for the degradation of malonyl-CoA in the presence of long chain acyl ACP. The acyl-ACP requirement for malonyl-CoA degradation activity was confirmed by shifting enoyl-ACP reductase mutants (fabI(Ts)) to the non-permissive temperature, leading to the abrupt cessation of fatty acid synthesis and the accumulation of malonyl-CoA in the absence of cerulenin. Analysis of the ACP pool composition before and after the temperature shift showed that the fabI block did not result in the accumulation of long chain acyl-ACP. These data indicate a feedback regulatory loop that functions to recycle malonyl-CoA to acetyl-CoA following the down-regulation of fatty acid and phospholipid formation and provides a physiological rationale for the acyl-ACP-dependent, malonyl-ACP decarboxylase reaction catalyzed by beta-ketoacyl-ACP synthases I and II. PMID- 7797549 TI - Spectroscopic studies of the characterization of recombinant human dihydrolipoamide dehydrogenase and its site-directed mutants. AB - In this paper, we report the overexpression and single-step purification of recombinant wild-type and site-directed mutants of human dihydrolipoamide dehydrogenase in Escherichia coli and detailed spectroscopic studies aimed at understanding the catalytic mechanism of this enzyme. One mutation (K37E) has been identified in a patient lacking dihydrolipoamide dehydrogenase activity and has been reported previously (Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., and Patel, M. S. (1993) Proc. Natl. Acad. Sci. USA. 90, 5186-5190), while the other two mutations were previously generated specifically to address the role of the active-site base (His-452) and its ion pair (Glu-457). Circular dichroic and fluorescence spectroscopic data illustrate the role of these amino acids in maintaining the structure and function of human dihydrolipoamide dehydrogenase. While mutant H452Q is severely crippled in catalysis of the physiological reaction, the reverse reaction is affected in the E457Q mutant. The K37E mutant shows very little deviation from the wild-type enzyme. PMID- 7797550 TI - Identification of the active site nucleophile in nucleoside 2 deoxyribosyltransferase as glutamic acid 98. AB - 2'-Fluoro-2'-deoxyarabinonucleosides are time-dependent inhibitors of nucleoside 2-deoxyribosyltransferase. 2,6-Diamino-9-(2'-deoxy-2'-fluoro-beta-D arabinofuranosyl)-9H-purine (dFDAP) inhibited the enzyme by formation of a primary complex (Kd = 140 microM) that isomerized to a secondary complex with a first-order rate constant of 0.2 min-1. Inhibited enzyme contained stoichiometric amounts of covalently bound 2'-fluoro-2'-deoxyarabinosyl moiety, recovered less than 5% of its activity after storage for a week at 5 degrees C, but regained over 70% of the lost activity by treatment with 600 microM Ade. 6-Amino-9-(2' deoxy-2'-fluoro-beta-D-arabinofuranosyl)-9H-purine (dFAdo) was a product of the reactivation reaction. Proteolysis of inhibited enzyme identified a modified fragment that spanned residues 82-107 which could not be sequenced past Gly-96. dFDAP-inhibited enzyme and enzyme reacted with normal substrates (i.e. dThd and dAdo) were hydrolyzed between Met-97 and Glu-98 by 0.1 M NaOH. These findings and model studies on the base lability of peptides containing glutamyl esters suggested that the gamma-carboxylate of Glu-98 was esterfied during catalysis. The role of Glu-98 was confirmed by changing this residue to alanine. The specific activity of wild-type enzyme was 3 orders of magnitude greater than that of the mutant enzyme. Collectively, chemical modification and mutagenesis studies have identified Glu-98 as the active site nucleophile of nucleoside 2 deoxyribosyltransferase. PMID- 7797551 TI - Nucleoside 2-deoxyribosyltransferase. Pre-steady-state kinetic analysis of native enzyme and mutant enzyme with an alanyl residue replacing Glu-98. AB - Nucleoside 2-deoxyribosyltransferase catalyzes cleavage of a 2' deoxyribosylnucleoside (A) to a nucleobase (P) with deoxyribosylation of the enzyme. Substrates quenched the intrinsic fluorescence of native enzyme (E) and a catalytically inactive mutant enzyme (E98A enzyme). The time courses of these reactions were analyzed in terms of the following scheme where EX is the 2 deoxyribosyl ester of Glu-98. [formula: see text] The initial complexes between E and dAdo, dGuo, dIno, and dCyd or those between EX and the corresponding nucleobases were formed in a rapid equilibrium step. Native enzyme and E98A enzyme bound 2'-deoxyribosylnucleosides with similar affinities (k-1/k1). From a comparison of the time-dependent fluorescence changes associated with the reaction of native enzyme or E98A enzyme with these substrate, the kinetic step for 2-deoxyribosylation of Glu-98 was identified (k2 and k-2). dThd and dUrd quenched the fluorescence of native enzyme in a biphasic process. The late phase of this reaction was associated with 2-deoxyribosylation of Glu-98. The pre steady-state kinetic constants calculated from fluorescence quenching data for dAdo and Cyt were consistent with the experimental values for the steady-state kinetic coefficients and the equilibrium constant of the reaction. PMID- 7797552 TI - The mobile group I intron 3 alpha of the yeast mitochondrial COXI gene encodes a 35-kDa processed protein that is an endonuclease but not a maturase. AB - Three mitochondrial mutants were characterized that block the splicing of aI3 alpha, a mobile group I intron of the COXI gene of yeast mtDNA. Mutant C1085 alters helical structures known to be important for splicing of group I introns. M44 and C1072 are point mutants in exon 3 that block correct splicing but allow some splicing at cryptic 5'-splice sites. M44 alters the P1 helix needed for 5' splice site definition, while the mutation in C1072 is a new kind of mutation because it is located upstream of the exon sequence involved in the P1 helix. All three mutants accumulate novel proteins of 35 and 44 kDa (p35 and p44, respectively) detected both by labeling of mitochondrial translation products and by Western blotting. Partial protease digestions indicate that p44 and p35 are closely related, probably as precursor and processed protein. The level of the intron-encoded endonuclease activity, I-SceIII, is elevated approximately 10-fold in the mutants. Partial purification of I-SceIII from the mutants showed that most, if not all, of the activity is associated with p35. Finally, because aI3 alpha splices accurately in a petite mutant, we conclude that aI3 alpha splicing does not depend on a mtDNA-encoded maturase. PMID- 7797554 TI - Transactivation domain 2 (TA2) of p65 NF-kappa B. Similarity to TA1 and phorbol ester-stimulated activity and phosphorylation in intact cells. AB - The p65 subunit of the inducible transcription factor NF-kappa B contains at least two strong transactivation domains (TADs) within its C terminus. The first domain, TA1, is contained within the last 30 amino acids of p65, whereas TA2 comprises the adjacent 90 amino acids. In this study, squelching experiments revealed that both TADs of p65, as well as the related subunit c-Rel, compete for the same cofactor(s) mediating transactivation. Both TADs of p65 share a common sequence motif, which is evolutionarily conserved and displays a remarkable degree of spatial organization when aligned on an alpha-helical surface. The functional importance of the common sequence motif was confirmed by deletion analysis of TA2. Within the conserved sequence motif, a 7-amino-acid repeat was noted. Idealized heptad repeats fused to the DNA binding domain of Gal4 were transcriptionally active, but only as multimers. Phosphorylation and transcriptional activity of a defined region within the TA2 domain was found to be stimulated by phorbol ester treatment of cells. In contrast, TA1 was constitutively phosphorylated, and its activity did not significantly respond to phorbol ester stimulation. The stimulatory effect of phorbol ester on transcription of the TA2 domain was completely blocked by the protein kinase C inhibitor. These data suggest that protein kinase C has a dual effect on NF-kappa B activity. It not only causes removal of I kappa B-alpha from cytoplasmic NF kappa B but also augments the transactivation potential of activated nuclear NF kappa B. PMID- 7797553 TI - Cloning of a cDNA for DNA supercoiling factor reveals a distinctive Ca(2+) binding protein. AB - DNA supercoiling factor is a protein capable of generating negative supercoils into a relaxed DNA in conjunction with eukaryotic DNA topoisomerase II. A cDNA clone encoding the Bombyx mori supercoiling factor has been isolated and characterized. The cDNA sequence contains an open reading frame of 322 amino acids rich in acidic residues. A local region of the predicted polypeptide shares a weak homology with the central portion of bacterial DNA gyrase A subunit. The cDNA sequence also predicts two direct repeats within the factor. Each repeat unit consists of a potential EF-hand domain. The factor contains three other potential EF-hand domains and actually binds Ca2+. Moreover, the supercoiling reaction has been shown to be activated by Ca2+. These results implicate Ca2+ in the control of the superhelical state of DNA. PMID- 7797555 TI - Cloning and characterization of COX14, whose product is required for assembly of yeast cytochrome oxidase. AB - Nuclear respiration-deficient mutants of Saccharomyces cerevisiae previously assigned to complementation group G93 lack cytochromes a and a3 and detectable cytochrome oxidase activity. Other respiratory chain carriers and the ATPase complex are present at near wild-type levels, indicating that the mutations specifically affect cytochrome oxidase. Since synthesis of the mitochondrially derived subunits 1, 2, and 3 of cytochrome oxidase is normal, the defect cannot be related to transcription of the endogenous genes or processing and translation of the corresponding RNAs. The results of Western analysis of the cytochrome oxidase subunits encoded in nuclear DNA also argues against an effect of the mutations on expression of these constituents. The G93 mutants are complemented by a nuclear gene, designated COX14. The product of this gene is a low molecular mass protein of 7,960 Da. A gene fusion expressing a biotinylated form of Cox14p complements cox14 mutants, indicating partial functional equivalence. The biotinylated derivative has been helpful in localizing Cox14p to the mitochondrial membrane and demonstrating that it is not a hitherto unrecognized subunit of cytochrome oxidase, although it does appear to be associated with a high molecular weight complex. This evidence, combined with the assembly-arrested phenotype of cox14 mutants, indicates that Cox14p, like several other recently described mitochondrial constituents, provides an important function at some late stage of the cytochrome oxidase assembly pathway. PMID- 7797557 TI - Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. AB - The Bacillus subtilis dlt operon (D-alanyl-lipoteichoic acid) is responsible for D-alanine esterification of both lipoteichoic acid (LTA) and wall teichoic acid (WTA). The dlt operon contains five genes, dltA-dltE. Insertional inactivation of dltA-dltD results in complete absence of D-alanine from both LTA and WTA. Based on protein sequence similarity with the Lactobacillus casei dlt gene products (Heaton, M. P., and Neuhaus, F. C. (1992) J. Bacteriol. 174, 4707-4717), we propose that dltA encodes the D-alanine-D-alanyl carrier protein ligase (Dcl) and dltC the D-alanyl carrier protein (Dcp). We further hypothesize that the products of dltB and dltD are concerned with the transport of activated D-alanine through the membrane and the final incorporation of D-alanine into LTA. The hydropathy profiles of the dltB and dltD gene products suggest a transmembrane location for the former and an amino-terminal signal peptide for the latter. The incorporation of D-alanine into LTA and WTA did not separate in any of the mutants studied which indicates that either one and the same enzyme is responsible for D-alanine incorporation into both polymers or a separate enzyme, encoded outside the dlt operon, transfers the D-alanyl residues from LTA to WTA (Haas, R., Koch, H.-U., and Fischer, W. (1984) FEMS Microbiol. Lett. 21, 27-31). Inactivation of dltE has no effect on D-alanine ester content of both LTA and WTA, and at present we cannot propose any function for its gene product. Transcription analysis shows that the dlt operon is transcribed from a sigma D-dependent promoter and follows the pattern of transcription of genes belonging to the sigma D regulon. However, the turn off of transcription observed before sporulation starts seems to be dependent on the Spo0A and AbrB sporulation proteins and results in a D-alanine free purely anionic LTA in the spore membrane. The dlt operon is dispensable for cell growth; its inactivation does not affect cell growth or morphology as described for L. casei. PMID- 7797556 TI - Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with Src and P85 alpha. AB - Following ligand binding, the epidermal growth factor receptor (EGF-R) autophosphorylates itself on tyrosine residues located in its carboxyl terminus; in vitro, three sites are highly phosphorylated, while two other sites are phosphorylated to lesser extents. In the presence of the Src protein-tyrosine kinase, in vitro phosphorylation of the minor autophosphorylation sites was increased, and four additional residues were phosphorylated. Following EGF stimulation, two (Tyr-891 and Tyr-920) were found to be phosphorylated in a colorectal cell line (DLD-1) and in a breast tumor cell line (MCF7). The remaining in vitro sites were not found to be highly phosphorylated in vivo. The sequences surrounding Tyr-891 and Tyr-920 match the reported consensus binding sequences for the SH2 domains of Src and the regulatory domain of phosphatidylinositol 3-kinase (p85 alpha), respectively. In vitro, both of these proteins were found to bind to Src-phosphorylated EGF-R with approximately 100 fold greater affinity than to autophosphorylated EGF-R, demonstrating that Src creates new sites for SH2 binding. Furthermore, Csk-inactivated Src was activated by interaction with Src-phosphorylated EGF-R but not by autophosphorylated EGF-R. Upon EGF treatment of MCF7 or three colorectal carcinoma cell lines (WiDr, DLD-1, and LS174T), the EGF-R coimmunoprecipitated with both p85 alpha and Src. Evidence is also presented that suggests that an EGF-R-related protein, ErbB2, may be involved in similar Src-mediated interactions. These data demonstrate that EGF-R is phosphorylated in vivo at non-autophosphorylation sites and that these novel sites can act as docking sites for Src, P85 alpha, and potentially other SH2 containing proteins. In addition, the data suggest a tyrosine phosphatase independent mechanism for the elevation of Src activity in cells exposed to growth factors. Overexpression of Src, EGF-R, and/or ErbB2 in breast and colorectal tumor cells suggests the potential that such interactions may contribute to the transformed phenotype of these carcinomas. PMID- 7797558 TI - Kidd blood group and urea transport function of human erythrocytes are carried by the same protein. AB - The gene encoding the urea transporter of human erythrocytes (HUT11 clone) has been cloned recently (Olives, B., Neau, P., Bailly, P., Hediger, M. A., Rousselet, G., Cartron, J. P., and Ripoche, P. (1994) J. Biol. Chem. 269, 31649 31652). Now, this gene has been assigned to chromosome 18q12-q21 by in situ hybridization, as also found for the Kidd (Jk) blood group locus. In coupled transcription-translation assays, the HUT11 cDNA directed the synthesis of a 36 kDa protein which was immunoprecipitated by a human anti-Jk3 antibody produced by immunized Jk(a-b-) donors whose red cells lack Kidd antigens. The anti-Jk3 antibody also immunoprecipitated a protein material of 46-60 kDa from all red cell membranes, except those from Jk(a-b-) cells. After N-glycanase digestion the 46-60-kDa component was reduced to 36 kDa. A rabbit antibody raised against the predicted NH2-terminal amino-acids of the HUT11 protein reacted on immunoblots with a 46-60-kDa component present in all human erythrocytes except those from Jk(a-b-) individuals. Jk(a-b-) red cells lack the Kidd/urea transport protein and have a selective defect of the urea transport capacity, but a normal water permeability and aquaporin-associated Colton blood group antigens. These findings indicate that the erythrocyte urea transporter is encoded by the Kidd locus and may have implications for the biology of urea transporters and their tissue specific regulation. PMID- 7797559 TI - Lysine-based structure in the proregion of procathepsin L is the recognition site for mannose phosphorylation. AB - The recognition of lysosomal enzymes by UDP-GlcNAc: lysosomal-enzyme GlcNAc-1 phosphotransferase (phosphotransferase) is mediated by a protein structure on lysosomal enzymes. It has been previously demonstrated that lysine residues are required for phosphorylation of procathepsin L and are a common feature of the site on many lysosomal proteins. In this work, the procathepsin L recognition structure was further defined by identification of the region of the protein containing the structure and the critical lysine residues involved. Removal of the cathepsin L propeptide by low pH-induced autocatalytic processing abolished phosphorylation. The addition of either the purified propeptide or a glutathione S-transferase-propeptide fusion protein to the processed protein restored phosphorylation. Mutagenesis of individual lysine residues demonstrated that two propeptide lysine residues (Lys-54 and Lys-99) were required for efficient phosphorylation of procathepsin L. By comparison of the phosphorylation rates of procathepsin L, lysine-modified procathepsin L, and the procathepsin L oligosaccharide, lysine residues were shown to account for most, if not all, of the protein-dependent interaction. On this basis, it is concluded that the proregion lysine residues are the major elements of the procathepsin L recognition site. In addition, lysine residues in cathepsin D were shown to be as important for phosphorylation as those in procathepsin L, supporting a general model of the recognition site as a specific three-dimensional arrangement of lysine residues exposed on the surface of lysosomal proteins. PMID- 7797560 TI - Domain closure in the catalytic chains of Escherichia coli aspartate transcarbamoylase influences the kinetic mechanism. AB - The closure of the two domains of the catalytic chains of Escherichia coli aspartate transcarbamoylase, which is critical for completion of the T-->R transition, is stabilized by salt-bridges between Glu-50 and both Arg-167 and Arg 234. Mutation of Glu-50 to Ala shifts the enzyme toward a low activity, low affinity state (Newton, C. J., and Kantrowitz, E. R. (1990) Biochemistry, 29, 1444-1451). Kinetic isotope effects (KIE) and equilibrium isotope exchange kinetics (EIEK) have been used to probe the dynamic properties of the Glu-50- >Ala enzyme. Unlike the behavior of the wild-type enzyme, the observed kinetic isotope effect for 13C versus 12C at the carbonyl group of carbamoyl phosphate (CP) increased upon the binding of ligands which promote the formation of the R state (Asp, N-phosphonacetyl-L-aspartate (PALA), or ATP). The maximum rate for the [14C]Asp<-->Carbamoyl aspartate (CAsp) exchange with the Glu-50-->Ala enzyme was 500-fold slower than for the wild-type enzyme; however, the rate for the [14C]CP<-->CAsp exchange was only 50-fold slower, reversing the relative rates observed with the wild-type enzyme. In addition, upon variation of substrate pairs involving Asp or CAsp, loss of inhibition effects in the CP<-->CAsp exchange indicated that the Glu-50-->Ala substitution caused the kinetic mechanism for the mutant enzyme to shift from ordered to random. Computer simulations of the EIEK data indicate that the Glu-50-->Ala mutation specifically causes strong decreases in the rates of catalysis and association-dissociation for Asp and CAsp, with minimal effects on the CP and Pi on-off rates. With substrates bound, the Glu-50-->Ala enzyme apparently does not attain a full R state conformation. The PALA-activated Glu-50-->Ala enzyme, however, exhibits substrate affinities comparable to those for the wild-type enzyme, but fails to restore the preferred order substrate binding. Unlike the wild-type enzyme, both the T and R-states of the Glu-50-->Ala enzyme contribute to catalysis. A third state, I, is proposed for the Glu-50-->Ala enzyme, in which random order substrate binding is exhibited, and the catalytic step contributes significantly to overall rate limitation. PMID- 7797561 TI - Identification of novel DNA binding targets and regulatory domains of a murine tinman homeodomain factor, nkx-2.5. AB - A murine cardiac-specific homeodomain gene named csx (Komuro, I., and Izumo. S. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 8145-8149) and nkx-2.5 (Lints, T. J., Parsons, L. M., Hartley, L., Lyons, I., and Harvey, R. P. (1993) Development 119, 419-431) was identified as a potential vertebrate homologue of Drosophila tinman, a mesoderm determination factor required for insect heart formation (Bodmer, R. (1993) Development 118, 719-729). Bacterial expression of the nkx-2.5 homeodomain allowed us to identify downstream DNA targets from a library of randomly generated oligonucleotides. High affinity nkx-2.5 DNA binding sites, 5'-TNNAGTG 3', represented novel binding sequences, whereas intermediate and weaker affinity sites, 5'-C(A/T)TTAATTN-3', contained the typical 5'-TAAT-3' core required by most homeodomain factors for DNA binding. We also observed that nkx-2.5 served as a modest transcription activator in transfection assays done in 10T1/2 fibroblasts with multimerized binding sites linked to a luciferase reporter gene. Functional dissection of nkx-2.5 revealed a COOH-terminal inhibitory domain composed mainly of clusters of alanines and prolines, which appeared to mask a potent activation domain composed of hydrophobic and highly charged amino acids. PMID- 7797562 TI - A conformational change in the junctional foot protein is involved in the regulation of Ca2+ release from sarcoplasmic reticulum. Studies on polylysine induced Ca2+ release. AB - We investigated both conformational changes in the junctional foot protein (JFP) and Ca2+ release from sarcoplasmic reticulum (SR) in parallel after stimulation of triadic vesicles by the JFP-specific ligand, polylysine. To monitor protein conformational change, the JFP was labeled in a site-directed fashion with the fluorescent conformational probe methylcoumarin acetate (MCA) (Kang, J. J., Tarcsafalvi, A., Carlos, A. D., Fujimoto, E., Shahrokh, Z., Thevenin, B. J.-M., Shohet, S. B., and Ikemoto, N. (1992) Biochemistry 31, 3288-3293). The induction of SR Ca2+ release by polylysine produced a rapid increase in the fluorescence intensity of the JFP-bound MCA. The polylysine concentration dependence of the fluorescence change was essentially the same as that of Ca2+ release, suggesting that the two events are tightly coupled. However, the rate constant of MCA fluorescence change was much larger than that of Ca2+ release; i.e. the conformational change preceded Ca2+ release. Prevention of protein conformational change by lysine (0.2 M) inhibited Ca2+ release from SR. Inhibition of Ca2+ release by Mg2+ (5 mM), however, had little effect on the conformational change. These results suggest that binding of polylysine to the JFP produces conformational changes in the protein, which in turn activates the Ca2+ channel, leading to Ca2+ release from the SR. PMID- 7797563 TI - Carboxypeptidase M is identical to the MAX.1 antigen and its expression is associated with monocyte to macrophage differentiation. AB - The two monoclonal antibodies MAX.1 and MAX.11 recognize cell surface antigens that are almost undetectable on monocytes but highly expressed on differentiated macrophages. Biochemical characterization revealed that both antibodies detect the same 58-64-kDa glycoprotein anchored to the plasma membrane by glycosyl phosphatidylinositol linkage. We purified the MAX.1/11 antigen by immunoaffinity chromatography using monoclonal antibody MAX.11. The NH2-terminal amino acid sequence was determined and turned out to be identical to the NH2-terminal sequence of the membrane-bound carboxypeptidase M. By precipitation with antibodies MAX.1 and MAX.11, membrane preparations of macrophages and placental microvilli were almost completely depleted of enzyme activity, indicating that the two antibodies indeed recognize carboxypeptidase M. Immunoreactivity of both antibodies correlates with the reported tissue distribution of enzyme activity. Expression of carboxypeptidase M on mRNA level and enzymatic activity markedly increase during in vitro differentiation of monocytes, according to the described increase in MAX.1 and MAX.11 antigen expression. Moreover, in vitro differentiated macrophages show the highest specific activity yet described in any tissue. In addition, carboxypeptidase M expression could be detected in HL 60, U937, and THP-1 myeloid cell lines. Vitamin D3-induced monocytic differentiation resulted in an increased carboxypeptidase M expression in all three cell lines. Further studies are needed to elucidate the functional role of carboxypeptidase M during monocytic differentiation and activation. PMID- 7797564 TI - An amino-terminal domain containing hydrophobic and hydrophilic sequences binds the signal recognition particle receptor alpha subunit to the beta subunit on the endoplasmic reticulum membrane. AB - The signal recognition particle receptor consists of two subunits of 72 kDa (SR alpha) and 30 kDa (SR beta). Assembly of SR alpha on the endoplasmic reticulum membrane can occur independent of the signal recognition particle-mediated translocation pathway. To identify the sequences within SR alpha necessary for membrane binding, a series of amino-terminal and internal deletion mutants was constructed and translated in a cell-free system. In addition, nascent SR alpha polypeptides of varying lengths were generated by cycloheximide treatment of translation reactions. Microsome binding assays performed on these polypeptides revealed a membrane binding domain consisting of the amino-terminal 140 residues of SR alpha. This domain includes the two hydrophobic sequences originally proposed to bind to membranes and a highly charged region not previously implicated in membrane assembly. Furthermore, the domain forms a protease resistant folding unit that after proteolysis can target and anchor onto microsomes. Extraction of microsomal SR alpha at high pH supplemented with 1 M NaSCN suggests that SR alpha and the membrane binding domain are not integrated in the endoplasmic reticulum membrane. The membrane binding domain is also the major site of tight binding with SR beta, suggesting that SR beta plays a role in the membrane assembly of SR alpha. PMID- 7797565 TI - The SH2 domains of Src family kinases associate with Syk. AB - Src family kinases (Lyn, Fyn, Lck, and Blk) and Syk, a tandem SH2 domain containing tyrosine kinase, have been demonstrated to be associated with the antigen receptor in B cells. Both of these categories of tyrosine kinases are presumed to be critical players in the process of antigen-mediated signal transduction. Cross-linking of membrane immunoglobulin on the surface of B cells leads to the activation of Lyn, Fyn, and Blk, which presumably associate with the cytoplasmic tails of the membrane immunoglobulin-associated Ig alpha/beta heterodimer. Receptor ligation also leads to the tyrosine phosphorylation and catalytic activation of Syk, but the mechanism of association of this kinase with the antigen receptor remains to be established. A number of phosphoproteins that can associate with the SH2 domains of Blk, Lyn, and Fyn have been described in activated B cells. We demonstrate here that Syk is one of the proteins in the lysates of activated B cells which bind to the SH2 domains of Src family kinases. Syk binds directly to the SH2 domain of Blk and complexes in vivo with Lyn and Blk in activated B cells. PMID- 7797567 TI - Simultaneous overexpression of copper- and zinc-containing superoxide dismutase and catalase retards age-related oxidative damage and increases metabolic potential in Drosophila melanogaster. AB - The objective of this study was to elucidate the nature of the mechanisms by which overexpression of copper- and zinc-containing superoxide dismutase (Cu,Zn SOD) and catalase extends life span of Drosophila melanogaster. Experimental flies containing single extra doses of Drosophila Cu,Zn-SOD and catalase genes were compared with appropriate controls at different ages. Overexpression of Cu,Zn-SOD and catalase caused a retardation in the accumulation of 8 hydroxydeoxyguanosine during aging and in response to the exposure of live flies to x-rays. The age-related loss of glucose-6-phosphate dehydrogenase activity (Glu-6-P dehydrogenase) and the increase in the rate of mitochondrial H2O2 generation were less steep in the experimental than control flies. The rate of in vivo oxygen consumption in the latter two-thirds of life span was higher in the experimental than in the control flies. Furthermore, the metabolic potential, or the total amount of oxygen consumed during an average life span, was about 30% greater in the experimental than the control flies. Altogether, results of this study indicate that overexpression of Cu,Zn-SOD and catalase ameliorates the age related accumulation of molecular oxidative damage and susceptibility to such damage in response to acute oxidative stress while prolonging the metabolic life of flies. The concept that oxidative stress is a causal factor in the aging process is supported. PMID- 7797566 TI - Myogenic regulatory factors can activate TATA-containing promoter elements via an E-box independent mechanism. AB - We have studied the effect of several myogenic regulatory factors on the activity of the promoter for a mouse gene encoding a skeletal myosin heavy chain (MyHC) expressed in adult (type IIB) muscle fibers. Co-transfection of myogenic factors is necessary for activity of the IIB promoter in mouse C2 myotubes in culture but not in quail myotubes in culture. Although this promoter contains one E-box within the first 192 base pairs upstream of the transcriptional start site, mutations in this motif demonstrate that it is not required for the transactivation effect of the myogenic factors. Analysis of other mutants suggests that the MEF2 and MHox DNA-binding factor binds to an evolutionarily conserved AT-rich motif. In addition, the IIB promoter appears to require the conserved TATA motif (CTATAAAAG) in order to be activated by the AT-rich sequences. The IIB promoter constructs produce RNA transcripts which begin at the natural site of transcriptional initiation in quail myotubes and in mouse C2 myotubes after co-transfection with myogenic factors; a second, minor, start site is also used in the co-transfected C2 myotubes. Results obtained after transfection of the mouse IIB promoter constructs in quail myotube cultures suggest that the overexpression of myogenic factors in C2 cultures does not result in an environment in which the control of IIB MyHC promoter activity is aberrant. Therefore, either the myogenic factors themselves, or other proteins induced by them, seem to interact directly with the basal transcription seem to interact directly with the basal transcription machinery to allow muscle-specific gene expression. PMID- 7797568 TI - A testicular protein important for fertility has glutathione S-transferase activity and is localized extracellularly in the seminiferous tubules. AB - A 24-kDa protein isolated by preparative gel electrophoresis from rat testes was reported by us as an active immunogen in rats. Anti-24-kDa antibodies inhibited murine sperm-oocyte binding in vitro. Here, we show similarity at the NH2 terminus shared by this protein purified on Sephadex G-75 followed by anion exchange high performance liquid chromatography with glutathione S-transferase (GST)-mu subunits. This protein purified by glutathione affinity chromatography also demonstrated similarity to GST-mu NH2 terminus in a 30-amino-acid overlap. Both proteins showed activity toward the GST substrate 1-chloro-2,4 dinitrobenzene (Km of 33 microM and 50 microM) which was inhibited by 17 beta estradiol 3-sulfate. Antisera against both proteins recognized liver GST-mu on Western blots and sperm acrosome of multiple species immunocytochemically. Both antisera significantly inhibited in vitro fertilization of goat oocytes by sperm preincubated with them while anti-liver GST sera did not. GST activity was localized on rat sperm, seminiferous tubular fluid, and Sertoli cells. Seminiferous tubular fluid 24-kDa protein shared similarity to the NH2 terminus of GST-mu subunits in a 20-amino-acid overlap. Time-dependent accumulation of GST was detected in the spent culture medium of seminiferous tubules from rats of different ages suggesting secretion. PMID- 7797569 TI - Retinol-binding protein and asialo-orosomucoid are taken up by different pathways in liver cells. AB - The intracellular transport and degradation of in vivo endocytosed retinol binding protein was compared with that of asialo-orosomucoid, a marker for receptor-mediated endocytosis through coated pits. The transport pathways were studied in rat liver cells by means of subcellular fractionation in Nycodenz and sucrose density gradients and by immunoelectron microscopy. Retinol-binding protein and asialo-orosomucoid were labeled by covalent attachment of radioiodinated tyramine cellobiose, an adduct which is incapable of crossing cellular membranes and thus provides a marker for the organelles where the protein has been taken up and degraded. The data obtained from subcellular fractionation studies, as well as from immunoelectron microscopy, showed that retinol-binding protein and asialo-orosomucoid were initially localized in different endocytic vesicles. Retinol-binding protein co-localized in density gradients with markers for potocytosis, an alternative endocytic pathway which uses internalization through caveolae instead of clathrin-coated pits. Later, retinol-binding protein and asialo-orosomucoid comigrated in the gradients and they were also observed in the same larger vesicles by immunoelectron microscopy. These data suggest that retinol-binding protein is taken up by liver cells by potocytosis and that a fraction of the retinol-binding protein is later transferred to larger vesicles located deeper in the cytoplasm where degradation takes place. PMID- 7797571 TI - A putative mammalian RNA helicase with an arginine-serine-rich domain colocalizes with a splicing factor. AB - We have cloned a rat cDNA whose deduced primary structure yields a protein of 117.4 kDa. Because this protein contains RNA helicase consensus motifs, among them a "DEAD" box, we have termed it HEL117 (for helicase of 117.4 kDa). Besides the helicase consensus motifs, HEL117 contains an arginine-serine (RS)-rich domain, which occurs in some proteins involved in RNA splicing. Moreover, the COOH-terminal region of 78 residues of HEL117 is 38.5% identical and 59% similar to the COOH-terminal region of a yeast PRP5 protein that is involved in RNA splicing. Rabbit antibodies generated against a synthetic peptide of HEL117 identified a single polypeptide not only in rat cells but also in cells of other mammals as well as chicken. The antibodies revealed a finely punctate and speckled intranuclear staining in immunofluorescence microscopy. A monoclonal antibody against a human splicing factor containing an RS domain (SC35) showed, in double immunofluorescence microscopy, largely overlapping staining consistent with HEL117 being involved in RNA splicing. PMID- 7797570 TI - Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. AB - Caveolae are flask-shaped plasma membrane specializations. A 22-kDa protein, caveolin, is a principal component of caveolar membranes in vivo. As recent evidence suggests that caveolae may participate in G protein-coupled signaling events, we have investigated the potential interaction of caveolin with heterotrimeric G proteins. Using cell fractionation techniques, we found that mutational or pharmacologic activation of Gs alpha prevents its cofractionation with caveolin. In a second independent approach, we directly examined the interaction of G proteins with caveolin. For this purpose, we recombinantly expressed caveolin as a glutathione S-transferase fusion protein. Using an in vitro binding assay, we found that caveolin interacts with G protein alpha subunits (Gs, Go, and Gi). Mutational or pharmacologic activation (with guanosine 5'-O-(thiotriphosphate)) of G alpha subunits prevents this interaction, indicating that the inactive GDP-bound form of G alpha subunits preferentially interacts with caveolin. This G protein binding activity is located within a 41 amino acid region of caveolin's cytoplasmic N-terminal domain (residues 61-101). Further functional analysis shows that a polypeptide derived from this region of caveolin (residues 82-101) effectively suppresses the basal activity of purified G proteins, apparently by inhibiting GDP/GTP exchange. This caveolin sequence is homologous to a region of the Rab GDP dissociation inhibitor, a known inhibitor of GDP/GTP exchange for Rab proteins. These data suggest that caveolin could function to negatively regulate the activation state of heterotrimeric G proteins. PMID- 7797572 TI - Interactions of phosphorylation and dimerizing domains of the alpha-subunits of Na+/K(+)-ATPase. AB - Chemical cross-linking studies are among a number of experimental approaches that have suggested the functional significance of higher association states of alpha,beta-protomers of Na+/K(+)-ATPase. Formation of the phosphointermediate of the enzyme on Asp369 of the alpha-subunit is known to induce oxidative cross linking of the alpha-subunits catalyzed by Cu(2+)-phenanthroline. To localize the phosphorylation-induced alpha,alpha-interface, we cleaved alpha at Arg438-Ala439 by controlled proteolysis and exposed the partially cleaved enzyme to the cross linking reagent. In addition to the alpha,alpha-dimer, two other phosphorylation induced cross-linked products were obtained. Using gel electrophoretic resolution of the cross-linked 32P-labeled enzyme, N-terminal analyses of the products, and their reactivities with sequence-specific antibodies, the two products were identified as a homodimer of the C-terminal 64-kDa fragment of alpha and a heterodimer of alpha and the 64-kDa peptide. The latter dimer was also obtained when the cross-linked alpha,alpha-dimer was formed first and then subjected to proteolysis. The findings localize the dimerizing domain to the C-terminal side of Ala439 and indicate that intersubunit proximities of dimerizing domains are regulated by phosphorylation-dephosphorylation of Asp369 during the reaction cycle of the enzyme. PMID- 7797573 TI - Dissociation of mitogen-activated protein kinase activation from the oxidative burst in differentiated HL-60 cells and human neutrophils. AB - In human polymorphonuclear leukocytes (PMNs), mitogen-activated protein kinases (MAPKs), also known as extracellular signal-regulated kinases (Erks), are activated within minutes upon stimulation with either chemoattractant formyl-Met Leu-Phe (fMLP) or phorbol 12-myristate 13-acetate (PMA). This activation of MAPKs coincides with the formation of superoxide anion, which occurs through the activation of a multiple-component NADPH oxidase pathway. MAPKs have thus been suggested to be involved in signal transduction leading to the oxidative burst. To investigate whether MAPK activation plays a central role in the oxidative burst, we evaluated the effect of cAMP on MAPK activation induced by fMLP and PMA. cAMP inhibits many PMN functional responses, including the oxidative burst, and has recently been shown to reduce growth factor- and PMA-induced MAPK activities in a variety of cells. We found that in differentiated, neutrophil like HL-60 cells, while cAMP reduced PMA-induced MAPK activation, it had no effect on fMLP-induced MAPK activation. Despite the presence of unchanged levels of activated MAPKs, the fMLP-induced oxidative burst was substantially diminished by cAMP. By contrast, O2-production induced by PMA remained the same even though MAPK activation was inhibited. In PMNs, although the levels of O2-induced by either 10 ng/ml or 100 ng/ml PMA were similar, only 100 ng/ml could stimulate MAPK activation, suggesting that the oxidative burst could occur in the absence of detectable activation of MAPKs. As in HL-60 cells, cAMP inhibited the O2 production in fMLP-stimulated PMNs but had no effect on MAPK activity. These results demonstrate that, while MAPK activation coincides with PMN activation, it can be dissociated from the oxidative burst. PMID- 7797574 TI - Identification of a major subfamily of large hsp70-like proteins through the cloning of the mammalian 110-kDa heat shock protein. AB - A major mammalian heat shock protein of 110 kDa (hsp110) has long been observed, but has not been cloned. We have cloned the hamster cDNA for hsp110 and show that it hybridizes on a Northern blot to a 3.5-kilobase heat-inducible message in hamster and mouse. The hsp110 sequence was found to share an approximately 30-33% amino acid identity with members of the hsp70 family, most of which occurs in the conserved ATP-binding domain of these molecules. In addition, five sequences were found to be highly similar to hsp110. These are the sea urchin egg receptor for sperm (Foltz, K.R., Partin, J. S., and Lennarz, W.J. (1993) Science 259, 1421 1425) and additional sequences from human and Caenorhaditis elegans and two from yeast. The carboxyl-terminal two-thirds of hsp110 and these five related proteins contain a pattern of highly conserved regions of sequence unique to this group. A probe containing these conserved sequences was found to strongly cross-react on a Southern blot with genomic sequences from yeast to man. A Western blot analysis of several murine tissues indicates that hsp110 is constitutively expressed in all mouse tissues and is highly expressed in brain. Therefore, hsp110 belongs to a new category of large and structurally unique stress proteins that are the most distantly related known members of the hsp70 family. PMID- 7797575 TI - Expression, domain structure, and enzymatic properties of an active recombinant human DNA topoisomerase II beta. AB - Human cells express two genetically distinct isoforms of DNA topoisomerase II, alpha and beta, which catalyze ATP-dependent DNA strand passage and are an important antitumor drug target. Here we report for the first time the successful overexpression of human topoisomerase II beta in yeast by cloning a topoisomerase II beta cDNA in a yeast shuttle vector under the control of a galactose-inducible promoter. Recombinant human topoisomerase II beta (residues 46-1621 fused to the first 5 residues of yeast topoisomerase II) was purified to homogeneity, yielding an enzymatically active polypeptide in sufficient quantity to allow analysis of its domain structure and comparison with that of recombinant human topoisomerase II alpha. Partial digestion of beta with either trypsin or protease SV8 generated fragments of approximately 130, 90, 62, and 45-50 kDa, arising from cleavage at three limited and discrete regions of the protein (A, B, and C) indicating the presence of at least four structural domains. Recombinant human topoisomerase II alpha and beta induced DNA breakage which was promoted by a variety of agents. Isoform differences in drug-induced DNA breakage were observed. These studies of human topoisomerase II beta in concert with alpha should aid the determination of their individual roles in cancer chemotherapy and should facilitate the design, targeting, and testing of cytotoxic antitumor agents. PMID- 7797576 TI - Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase. AB - The low-density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism. A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (apo) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1. The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits. Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL. However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor. CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C. Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor. Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect. Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor. These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL. The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues. PMID- 7797577 TI - Mammalian brain-specific L-proline transporter. Neuronal localization of mRNA and enrichment of transporter protein in synaptic plasma membranes. AB - The expression of a high affinity Na(+)- (and Cl-) dependent L-proline transporter (PROT) in subpopulations of putative glutamatergic pathways in rat brain raises the possibility of a specific physiological role(s) for this carrier in excitatory neurotransmission (Fremeau, R. T., Jr., Caron, M. G., and Blakely, R. D. (1992) Neuron 8, 915-926). However, the biochemical properties and regional, cellular, and subcellular distribution of the PROT protein have yet to be elucidated. Here, we document the brain-specific expression and neuronal localization of rat PROT mRNA. We also report the first identification and partial biochemical characterization of the mammalian brain PROT protein. An affinity-purified antipeptide antibody was produced that specifically recognized a single 68-kDa PROT protein on immunoblots of rat and human brain tissues. Deglycosylation of rat hippocampal membranes with peptide-N-glycosidase F reduced the apparent molecular mass of the native PROT protein from 68 to 53 kDa, the size of the primary PROT translation product determined by in vitro translation of the rat PROT cDNA in the absence of microsomes. Subcellular fractionation studies demonstrated that the PROT protein was enriched in synaptic plasma membranes but absent from postsynaptic densities. A differential distribution of PROT mRNA and protein was observed in rat striatum, suggesting that the transporter protein is synthesized in neuronal cell bodies in the cortex and exported to axon terminals in the caudate putamen. These findings warrant the consideration of a novel presynaptic regulatory role for this transporter in excitatory synaptic transmission. PMID- 7797578 TI - Identification of key charged residues of human interleukin-5 in receptor binding and cellular activation. AB - Interleukin-5 (IL-5) is a cytokine that plays a major role in the differentiation and activation of eosinophils. In order to identify which charged residues of human IL-5 are important in binding to its receptor and subsequent cellular activation, we have systematically replaced all of the clusters of charged amino acids with alanine residues. The mutants have been expressed in Escherichia coli, renatured, and purified. They were assayed for ability to cause proliferation of the erythroleukaemic cell line TF-1 and the up-regulation of eosinophil adhesion to ICAM-1. In addition, we studied receptor binding using either immobilized recombinant IL-5 receptor alpha-chain or the alpha/beta-receptor complex expressed on TF-1 cells. The key charged residue involved in binding to the beta chain of the receptor is Glu-12. This residue is in an identical position to those previously identified in IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in binding to the receptor beta-chain. The alpha-chain binding site is shown to involve the side chains Arg-90 and Glu-109, located in the second beta sheet and after the end of the fourth helix, respectively. It is unique to IL-5 and does not occur in IL-3 or GM-CSF. Understanding the topology of the interaction of IL-5 with its receptor chains will help in the search for rationally designed antagonists of IL-5 function. PMID- 7797579 TI - The activation-resistant conformation of recombinant human plasminogen is stabilized by basic residues in the amino-terminal hinge region. AB - Fully activable recombinant human plasminogen (rPlg) was expressed in mammalian cells employing either recombinant vaccinia virus or stable lines coexpressing alpha 2-plasmin inhibitor. A panel of eight variants of rPlg was constructed, in which progressively up to 6 basic amino acid residues in the hinge region of rPlg between the NH2-terminal acidic domain ("proactivation peptide") and kringle 1 were substituted by neutral residues. Analysis of the cleavage rates of these variants by plasmin revealed that the peptide bond at Arg68 is most susceptible, followed by Lys62 and Lys77. A variant with all 6 basic residues substituted was cleaved at Lys20. Three of these variants, PlgB (R68A, R70A), PlgF (R68A, R70A, K77H, K78H), and PlgG (R61A, K62A, R68A, R70A, K77H, K78H), as well as rPlg, were analyzed in more detail. The conformation of these plasminogens was analyzed by monitoring the change in intrinsic fluorescence upon binding of lysine analogs. This revealed that rPlg exhibits the native tight Glu1-plasminogen conformation, whereas PlgB, PlgF, and Plg G display an open conformation similar to Lys78 plasminogen, leading to an increased affinity for lysine analogs. This allowed a direct study of the impact of the activation-resistant conformation on the properties of Glu1-plasminogen. The open conformation of rPlg variants leads to an increased rate of activation by urokinase-type plasminogen activator and streptokinase and increased binding to a fibrin clot. Fibrin clot lysis mediated by tissue-type plasminogen activator was accelerated for the variants as a result of a lower Km for tissue-type plasminogen activator-mediated plasminogen activation, resulting from the increased affinity of rPlg (variants) for intact fibrin. We conclude that the basic residues in the extremely plasmin susceptible hinge region of plasminogen are directly involved in maintaining the activation resistant Glu1-plasminogen conformation. PMID- 7797580 TI - Simian virus 40 T antigen-induced amplification of pre-parietal cells in transgenic mice. Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. AB - Gastric units in the glandular epithelium of the mouse stomach contain several types of continuously renewing epithelial cells. Acid-producing parietal cells are derived from a multipotent stem cell that also gives rise to mucus-producing pit cells and pepsinogen- and intrinsic factor-producing zymogenic cells. We used nucleotides -1035 to +24 of the mouse H+/K(+)-ATPase beta subunit gene (H+/K(+) ATPase beta subunit-1035 to +24) to examine the consequences of expressing simian virus 40 T antigen (SV 40 TAg) in the normally rare, nonproliferating, short lived pre-parietal cell progenitor. Light and electron microscopic morphologic studies plus multilabel immunohistochemical analyses of postnatal day (P) 14-80 day transgenic mice revealed that SV40 TAg produces a 50-70-fold amplification of pre-parietal cells which become the predominant cell type in gastric units. Differentiation to mature parietal cells is blocked, resulting in hypochlorhydria and an associated systemic iron deficiency. SV40 TAg-induced pre-parietal proliferation is accompanied by apoptosis. Examination of adult transgenic mice homozygous for p53 wild type or p53 null alleles established that the apoptosis occurs through a p53-independent pathway. H+/K(+)-ATPase beta subunit -1035 to +24/SV40 Tag is not expressed during differentiation of the zymogenic lineage. Nonetheless, P28-P80 transgenic mice exhibit an apparent block in the conversion of pre-zymogenic to zymogenic cells. This block appears to be quite specific: conversion of preneck to neck cells and neck to pre-zymogenic cells is not affected. Comparison of normal and transgenic mice that are p53+/+ or p53-/- confirmed that the loss of mature zymogenic cells is not dependent upon p53. Although H+/K(+)-ATPase beta subunit -1035 to +24 is not active in pit cell progenitors or their differentiated descendants, there is a 2-3-fold increase in mature pit cells in transgenic animals. Our findings (i) demonstrate an approach for amplifying and characterizing pre-parietal or other progenitor cell populations in gastric units, (ii) reveal an SV40 TAg-inducible, p53-independent apoptotic mechanism that operates in a committed epithelial progenitor cell, and (iii) provide a transgenic mouse model for defining factors that may mediate progression through specific points in the differentiation programs of the parietal and zymogenic cell lineages or that may influence decisions about allocation to the pit cell lineage. PMID- 7797581 TI - Biochemical and molecular characterization of a barley seed beta-glucosidase. AB - A 60-kDa beta-glucosidase (BGQ60) was purified and characterized from seeds of barley (Hordeum vulgare L.). BGQ60 catalytic activity was restricted to the cleavage of short-chain oligosaccharides composed of (1-2)-, (1-3)-, and/or (1-4) beta-linked glucose or mannose units. These oligosaccharides are the primary products of endosperm cell wall polysaccharide hydrolysis by other enzymes. In keeping with this, complete hydrolysis of the major polysaccharide of barley starchy endosperm cell wall, (1-3,1-4)-beta-glucan, to free glucose was shown to require the concerted action of endo-(1-3,1-4)-beta-glucanase and BGQ60. The complete amino acid sequence of BGQ60 was determined by protein sequencing combined with the deduced sequence of the corresponding cDNA and genomic clones. The BGQ60 primary structure exhibits extensive homology to members of glycosyl hydrolase family 1 (EC 3.2.1.21). Southern and Northern blot analysis with the cDNA as probe indicated that BGQ60 is encoded by a single gene, and that BGQ60 mRNA only accumulates in the starch endosperm tissue of late developing seeds. The bgq60 structural gene of approximately 5 kilobases contains an open reading frame encoding 485 amino acids interrupted by 9 introns. The complete nucleotide sequence of the bgq60 structural gene represents the first characterized plant gene encoding a beta-glucosidase. The barley BGQ60 is a novel plant beta glucosidase with a hitherto undescribed specific enzymatic activity. The possible biological functions of BGQ60 during barley seed development and germination are discussed. PMID- 7797582 TI - Proteolysis of glucagon within hepatic endosomes by membrane-associated cathepsins B and D. AB - The acidic glucagon-degrading activity of hepatic endosomes has been attributed to membrane-bound forms of cathepsins B and D. Endosomal lysates processed full length nonradiolabeled glucagon to 32 different peptides that were identified by amino acid analysis and full-length sequencing. These indicated C-terminal carboxypeptidase, endopeptidase as well as N-terminal tripeptidyl-aminopeptidase activities in endosomes. Glucagon proteolysis was inhibited 95% by E-64 and pepstatin A, inhibitors of cathepsins B and D, respectively. This was confirmed by the pH 6-dependent chemical cross-linking of [125I]iodoglucagon to a polypeptide of 30 kDa, which was immunodepleted by polyclonal anti-cathepsin B antibody, and the removal of greater than 80% of glucagon-degrading activity by polyclonal antibodies to cathepsins B and D. By similar criteria, insulin degrading enzyme was ruled out as a candidate enzyme for endosomal proteolysis of glucagon. Lysosomal contamination was unlikely since all forms of cathepsin B in endosomes, i.e. the major 45-kDa inactive precursor as well as the lesser amounts of the 32- and 28-kDa active forms, were tightly bound to endosomal membranes. Furthermore the mature 29-kDa single-chain and 22-kDa heavy-chain forms of cathepsin L were undetectable in endosomes, although high levels of the 37-kDa proform were observed. Membrane association of the cathepsins B and D was not to the mannose 6-phosphate receptor since association was unaffected by mannose 6 phosphate and/or EDTA, thereby indicating a distinct endosomal receptor. Hence, a pool of active cathepsins B and D as well as a poorly defined tripeptidyl aminopeptidase is maintained in endosomes by selective membrane retention. These hydrolases degrade glucagon internalized into liver parenchyma early in endocytosis. PMID- 7797583 TI - A nucleotide sequence essential for the function of DRE, a common promoter element for Drosophila DNa replication-related genes. AB - Promoter regions of the Drosophila proliferating cell nuclear antigen (PCNA) gene and the DNA polymerase alpha 180-kDa catalytic subunit gene contain a common 8 base pair (bp) promoter element, 5'-TATCGATA (DRE, Drosophila DNA replication related element). We have generated various base substitutions and internal deletions in and around DRE (nucleotide positions -93 to -100 with respect to the transcription initiation site) of the PCNA gene in vitro and subsequently examined their effects on the binding to DREF (DRE-binding factor) and PCNA gene promote activity in cultured Drosophila Kc cells as well as in living flies. Gel mobility shift assays using nuclear extracts of Kc cells with and without competitor DNA fragments carrying the mutations indicated that the 10-bp sequence from positions -91 to -100 is essential for complex formation with DREF. Transient expression assays of chloramphenicol acetyl-transferase (CAT) in Kc cells transfected with PCNA promoter-CAT fusion genes carrying the mutations revealed that the 8-bp sequence from -93 to -100 is essential for activation of the promoter in Kc cells. Examination of lacZ expression from PCNA promoter-lacZ fusion genes carrying the mutations, introduced into flies by germ-line transformation, revealed that the 8-bp sequence is also important for DRE function during development. However, we obtained two exceptional mutations in the 8-bp sequence that did not or only marginally affected the PCNA gene promoter activity in transgenic flies. Both of these mutations effectively reduced the promoter activity in CAT transient expression assay in Kc cells and the binding to DREF in vitro. Therefore, the 8-bp sequence requirement for DRE function appears to be less stringent in living flies than in the cultured cell or in vitro cases. PMID- 7797584 TI - A cis-acting element in Rous sarcoma virus long terminal repeat required for promoter repression by HeLa nuclear protein p21. AB - HeLa cell basic nuclear protein (p21), which represses Rous sarcoma virus long terminal repeat (RSV LTR) promoter activity, diminished v-src expression and the appearance at permissive temperature of the transformed phenotype in tsRSVLA23 Rat-1, a cell line transformed with a temperature-sensitive mutant of RSV. Nuclear run-on analyses using COS-1 cells cotransfected with p21 cDNA and chloramphenicol acetyltransferase reporter indicated that p21 inhibits transcription initiation by targeting a region in the RSV LTR promoter between positions -108 and -85 upstream of the cap site. Insertion of this 24-base pair sequence in place of one of the 72-base pair enhancers in the SV40 early promoter rendered it sensitive to p21 repression. Electrophoretic mobility shift assays using a synthetic oligomer corresponding to the 24-base pair LTR promoter element revealed that p21 altered the pattern of protein.DNA complex formation apparently without binding DNA directly. Complex formation assayed by UV cross-linking and DNA affinity chromatography indicated further that a cellular factor which can interact with this element was decreased in cells transfected with p21 expression plasmid. The results indicate that p21 repression of RSV LTR is mediated by a cis acting element and may occur by alteration of protein complexes formed on this promoter element. PMID- 7797585 TI - Secretion and maturation study of endothiapepsin in Saccharomyces cerevisiae. A first step toward improving its substrate specificity. AB - The gene encoding endothiapepsin (EAP), an extracellular aspartic proteinase from the filamentous ascomycete Cryphonectria parasitica, was expressed into Saccharomyces cerevisiae. Efficient secretion of an active and correctly processed enzyme was achieved when expressing the entire cDNA encoding prepro-EAP under the control of the galactose-inducible GRAP1 yeast promoter. Since three independent, site-directed mutations of EAP, including the substitution of an aspartyl catalytic residue, resulted in the intracellular accumulation of zymogen forms, we assumed that the EAP propeptide was autocatalytically processed. As a prerequisite to further improve the specificity of EAP, we therefore attempted to bypass this self-processing step in three different ways: 1) introduction of a Kex2-like recognition site between the pro and the mature part, 2) deletion of the prosequence (pre-EAP), and 3) co-expression in trans of the pre-EAP with its preprosequence. No improvement in the secretion of mutant enzymes was obtained in any of these experiments. As an alternative, we finally replaced the EAP processing site by the chymosin cleavage sequence of kappa-casein. Such a modification remained efficient in directing the secretion of active EAP only when a putative alpha-helix structural motif was conserved at the C terminus of the pro region. PMID- 7797587 TI - The tumor suppressor maspin does not undergo the stressed to relaxed transition or inhibit trypsin-like serine proteases. Evidence that maspin is not a protease inhibitory serpin. AB - The role of tumor suppressor proteins in the development of malignancy has made the understanding of their molecular mechanisms of action of great importance. Maspin is a tumor suppressor produced by a number of cell types of epithelial origin. Exogenous recombinant maspin has been shown to block the growth, motility, and invasiveness of breast tumor cell lines in vitro and in vivo. Although belonging to the the serine proteinase inhibitor (serpin) superfamily of proteins, the molecular mechanism of maspin is currently unknown. Here we show that the reactive site loop of maspin exists in an exposed conformation that does not require activation by cofactors. The reactive site loop of maspin, however, does not act as an inhibitor of proteinases such as chymotrypsin, elastase, plasmin, thrombin, and trypsin but rather as a substrate. Maspin is also unable to inhibit tissue and urokinase type plasminogen activators. Stability studies show that maspin cannot undergo the stressed-relaxed transition typical of proteinase-inhibitory serpins, and the protein is capable of spontaneous polymerization induced by changes in pH. It is likely, therefore, that maspin is structurally more closely related to ovalbumin and angiotensinogen, and its tumor suppressor activity is independent of a latent or intrinsic trypsin-like serine proteinase-inhibitory activity. PMID- 7797586 TI - Purification and characterization of a rat liver enzyme that hydrolyzes valaciclovir, the L-valyl ester prodrug of acyclovir. AB - Valaciclovir is an oral prodrug of the antiherpetic agent acyclovir. An enzyme that hydrolyzes valaciclovir to acyclovir, valaciclovir hydrolase (VACVase), was purified from rat liver and characterized. VACVase was a basic (pI 9.4) protein associated with mitochondria. It was monomeric and had a molecular mass of 29 kDa. Amino acid sequences of six VACVase peptides, including its NH2 terminus (13 amino acids) and accounting for approximately 20% of its complete sequence, were not found in the SwissProt protein data base. VACVase hydrolyzed other amino acid esters of acyclovir in addition to valaciclovir (kcat/Km = 58 mM-1 s-1), with a preference for the L-alanyl (kcat/Km = 226 mM-1 s-1) and L-methionyl (kcat/Km = 200 mM-1 s-1) esters. It did not hydrolyze other types of esters or numerous di- and tripeptides and aminoacyl-beta-naphthylamides. Hydrolysis of valaciclovir by VACVase was not inhibited by amastatin, antipain, aprotinin, bestatin, chymostatin, E-64, EDTA, ebelactone A, ebelactone B, elastatinal, leupeptin, pepstatin, or phosphoramidon. It was neither inhibited nor activated by Ca2+, Co2+, Mg2+, Mn2+, or Zn2+. Therefore, this enzyme is not a typical esterase or peptidase and, to our knowledge, it has not been described previously. Its physiological function is not known; however, it may play a significant role in the biotransformation of valaciclovir to acyclovir. PMID- 7797589 TI - Decreased phosphorylation of mutant insulin receptor by protein kinase C and protein kinase A. AB - We have recently reported that the Arg1152-->Gln insulin receptor mutation (QK single mutant) alters a conserved motif (RK motif) immediately next to the key tyrosine phosphorylation sites (Tyr1146, Tyr1150, Tyr1151) of the receptor and constitutively activates its kinase and metabolic signaling. To investigate further the function of the RK motif, we have expressed two additional mutant insulin receptors: a single mutant, in which the second basic residue in the RK motif (Lys1153) was substituted (RA mutant); and a double mutant, in which both the Arg and the Lys residues were replaced with noncharged amino acids (QA mutant). As compared with the transfected wild-type receptors (WT), both the single and the double mutant receptors were normally synthetized and transported to the plasma membrane and bound insulin normally. Whereas the double mutant receptor exhibited preserved insulin-dependent autophosphorylation, kinase activity, and 2-deoxyglucose uptake, all of these functions were grossly impaired in the two single mutant receptors. Two-dimensional analysis of tryptic phosphopeptides from receptor beta-subunits revealed that decreased autophosphorylation of the single mutant receptors mainly involved regulatory Tyr1150,1151 and carboxyl-terminal Tyr1316,1322. At variance with the insulin stimulated, insulin-independent tyrosine kinase activity toward poly(Glu-Tyr) 4:1 was increased 3-fold in both the double and the single mutants. All mutant receptors induced a 2-fold increase in basal 2-deoxyglucose uptake in NIH-3T3 cells. Treatment of WT transfected cells with 12-O-tetradecanoyl-phorbol-13 acetate or 8-bromo-cAMP increased insulin receptor phosphorylation by 3-fold. No phosphorylation was observed in cells expressing the two single or the double mutant receptor. Consistently, purified preparations of PKC and PKA phosphorylated the WT but not the mutant receptors in vitro. A 17-amino acid synthetic peptide encoding the receptor sequence surrounding the RK motif inhibited phosphorylation of WT insulin receptors by both protein kinases A and C. A mutant peptide in which the RK sequence was replaced by QK (to mimic the mutation in the QK receptor) exhibited no inhibitory effect. Thus, the RK insulin receptor motif is required for insulin receptor phosphorylation by protein kinases C and A and may modulate insulin-independent receptor activity. The RK motif may also have an important structural role in allowing normal insulin regulation of the kinase. PMID- 7797588 TI - Two distinct cell attachment sites in entactin are revealed by amino acid substitutions and deletion of the RGD sequence in the cysteine-rich epidermal growth factor repeat 2. AB - The basement membrane glycoprotein, entactin, has previously been shown to promote cell attachment and chemotaxis. We have constructed a panel of glutathione S-transferase fusion proteins that encompasses the four major structural domains of entactin, G1, G2, E, and G3. These proteins have been synthesized in bacteria and purified by affinity chromatography. The connecting stalk of entactin, E, which contains four cysteine-rich EGF homology repeats and the integrin receptor RGD recognition sequence, has been modified by deletion of the RGD sequence and substituting glutamic acid for aspartic acid. Attachment assays reveal that the RGD sequence is one of the major cell attachment sites in entactin and that this sequence is recognized by the alpha v beta 3 integrin receptor. Analysis of cell attachment on mutant forms of full-length entactin expressed in the baculovirus expression system revealed a second attachment site that was independent of the RGD sequence. This second site was localized to a peptide of 39 amino acid residues in the second globular G2 domain of entactin. This peptide represents a cysteine-rich EGF repeat. Inhibition of cell attachment by anti-integrin receptor antibodies indicates that the second attachment site is recognized by a member of the beta 1 family of integrin receptors, possibly alpha 3 beta 1. PMID- 7797591 TI - Irradiation increases manganese superoxide dismutase mRNA levels in human fibroblasts. Possible mechanisms for its accumulation. AB - Irradiation induces the production of superoxide radicals (O2.-), which play an important causative role in radiation damage. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme involved in scavenging O2..-. This study examined MnSOD gene regulation by irradiation in WI38 human fibroblasts. Unstimulated fibroblasts constitutively expressed MnSOD activity and mRNA; irradiation markedly increased MnSOD activity and mRNA levels. The increase in MnSOD transcripts by irradiation was both time- and dose-dependent. WI38 fibroblasts constitutively produce low levels of interleukin-1 (IL-1). The induction of MnSOD mRNA by irradiation was partially blocked by anti-IL-1 antibodies, and treatment of cells with IL-1 also increased MnSOD mRNA levels. Inhibition of the cyclo-oxygenase pathway with indomethacin augmented the induction MnSOD mRNA by irradiation and prostaglandin E2 inhibited the accumulation of MnSOD mRNA by irradiation. Transcriptional run-on analysis showed that irradiation increased the rate of MnSOD transcription 2-fold. Stability studies of MnSOD mRNA in these cells showed that the half-life increased from < 1.5 h in unirradiated cells to > 4 h in irradiated cells. These results suggest that induction of the MnSOD gene after irradiation is regulated, at least in part, by IL-1 production and that increased levels of MnSOD transcripts also occur through a pathway of endogenous prostaglandin E2 production. Our data indicate that the increase in MnSOD mRNA observed after irradiation occurs through both transcriptional and post-transcriptional mechanisms. PMID- 7797590 TI - Regulation of neurite outgrowth and SNAP-25 gene expression by the Brn-3a transcription factor. AB - SNAP-25 is a presynaptic nerve terminal protein which is also essential for the process of neurite outgrowth in vivo and in vitro. However the processes regulating its expression have not been characterized previously. We show that the gene encoding this protein, SNAP, is strongly activated by the Brn-3a POU (Pit-Oct-Unc) family transcription factor. Expression of both Brn-3a and SNAP-25 increases when ND7 neuronal cells are induced to extend neurite processes by serum removal. Inhibition of Brn-3a expression in these cells inhibits SNAP-25 expression and abolishes the neurite outgrowth that normally occurs in response to serum removal. These results identify Brn-3a as the first transcription factor having a role in process outgrowth in neuronal cells acting, at least in part, via the activation of SNAP-25 gene expression. PMID- 7797592 TI - Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases. AB - Cysteine proteases related to mammalian interleukin-1 beta-converting enzyme (ICE) and the nematode cell death abnormal ced-3 gene product have been implicated in the effector mechanism of apoptotic cell death. Two novel members of this new family of ICE/CED-3-related proteases, designated ICErel-II and ICErel-III, were cloned from human monocytic cells. Both were highly homologous to human ICE (52% identical) and CED-3 (25% identical) and both contained the absolutely conserved pentapeptide sequence Gln-Ala-Cys-Arg-Asp containing the catalytic cysteine residue. Other structural motifs that were comparable with ICE suggest that ICErel-II and ICErel-III are also synthesized as larger proenzymes which are proteolytically processed to form heterodimeric active enzymes. Pro interleukin-1 beta processing activity could not be detected in cells transfected with ICErel-II or ICErel-III, but pro-domain-less truncated forms of ICErel-II and ICErel-III were capable of effectively inducing fibroblast apoptosis. ICErel II and ICErel-III may, therefore, participate in proteolytic events culminating in the apoptotic death of human cells. PMID- 7797593 TI - Characterization of the murine mu opioid receptor gene. AB - The analgesic and addictive properties of morphine and other opioid drugs are thought to result from their interaction with mu opioid receptors. Using a delta opioid receptor cDNA as a probe, we have isolated a murine mu opioid receptor cDNA clone (mMOR). Stable expression of mMOR in Chinese hamster ovary cells conferred high binding affinity for mu receptor ligands including morphine and [D Ala2,N-methyl-Phe4,Gly5-ol]-enkephalin and low affinity for delta and kappa preferring ligands. Treatment of these cell lines with morphine and other mu agonists inhibited forskolin-induced cAMP accumulation, demonstrating a functional coupling of mMOR to the inhibition of adenylate cyclase. The predicted amino acid sequence of mMOR shares approximately 55% overall amino acid identity with the delta receptor and approximately 97% identity with the recently reported rat mu opioid receptor. Expression of the mu receptor in mouse brain as revealed by in situ hybridization parallels the reported pattern of distribution of mu selective ligand binding sites. Chromosomal localization (to mouse chromosome 10) and Southern analysis are consistent with a single mu opioid receptor gene in the mouse genome, suggesting that the various pharmacologically distinct forms of the mu receptor arise from alternative splicing, post-translational events, or from a highly divergent gene(s). PMID- 7797594 TI - The COOH-terminal domain of the RNA polymerase alpha subunit in transcriptional enhancement and deactivation at the bacteriophage T4 late promoter. AB - Many activator proteins generate their positive control of transcription through interactions with the COOH-terminal domain of the Escherichia coli RNA polymerase alpha subunit. We have examined the participation of this alpha-domain in transcriptional enhancement and suppression at bacteriophage T4 late promoters. Enhancement is generated by the T4 gene 45 protein, which is the DNA-tracking processivity factor of viral DNA replication; suppression of unenhanced transcription is generated by the RNA polymerase-binding co-activator T4 gene 33 protein. Enhanced and unenhanced transcription by RNA polymerase reconstituted with intact and truncated alpha subunits and by RNA polymerase containing ADP ribosylated alpha has been compared; the internal structures of transcription complexes formed with these RNA polymerases have also been analyzed by footprinting and photocross-linking. Comparison of these structural and functional analyses suggests that enhancement of T4 late transcription by gp45 is not compatible with any significant role of the COOH-terminal domain of the RNA polymerase core alpha subunit in transcriptional initiation. Suppression of unenhanced T4 late transcription by the gene 33 protein also does not require the COOH-terminal domain of alpha. PMID- 7797595 TI - Maturation of pre-tRNA(fMet) by Escherichia coli RNase P is specified by a guanosine of the 5'-flanking sequence. AB - The C+1/A+72 base pair at the top of the acceptor stem of Escherichia coli tRNA(fMet) accounts for several of the specialized roles of this tRNA in translation initiation. According to the rules of RNA substrate recognition by RNase P, the C+1/A+72 pair is likely to disfavor the 5'-maturation of pre tRNA(fMet). Indeed, in contrast to other E. coli tRNA species, tRNA(fMet) was not properly matured when overproduced from a multicopy expression vector. Half of the recovered tRNA(fMet) retained an extension at the 5' side. Such a defect of tRNA(fMet) processing could be cured by changing bases C+1 and A+72 by a Watson Crick base pair or by non-paired bases, provided one of them was a G. It could also be compensated by either (i) over-expression of RNase P or (ii) introduction within the plasmid of one out of the three 5'-flanking sequences naturally occurring in the four E. coli tRNA(fMet) genes. The effect of these flanking sequences on the maturation of tRNA(fMet) could be accounted for by the presence of a G located 2 bases upstream from C+1. Notably, this G is the only residue that is conserved in the 5'-flanking sequences of all four E. coli tRNA(fMet) genes. PMID- 7797596 TI - A possible multiclonal development in human colonic carcinomas. AB - In order to define whether all colonic tumors develop from a single transformed cell, we compared two sites each in 40 early-stage colonic carcinomas by K-ras mutation and DNA ploidy pattern. These 40 colonic carcinomas consisted of 26 protruding-type carcinomas and 14 superficial-type carcinomas. The two sites were selected in every tumor tissue and then DNA ploidy pattern and occurrence of K ras mutation were detected. In cases of "cancer in adenoma", we compared clonality between cancer cells and adenoma cells. In a cytofluorometrical study, it was shown that diploid patterns were predominantly seen in protruding-type carcinomas (76.9%), whereas many superficial-type carcinomas (64.3%) consisted of aneuploid cells. K-ras mutations were more frequently observed in protruding-type carcinomas: 42.3% in protruding-type compared to 21.4% in superficial-type carcinomas. These findings suggested that superficial-type carcinomas have a different mode of carcinogenesis from that of protruding-type carcinomas. Frequently, each pair of sites of the carcinoma tissue carried the same K-ras mutation, and DNA ploidy patterns were essentially the same. However, we encountered some cancers that showed different K-ras mutations in the cancer tissues. In particular, one case of cancer in adenoma demonstrated different K ras mutations in the cancer and adenoma tissue. These findings suggest that most colonic cancers develop monoclonally, but there are a few cancers (fewer than 5%) that start multiclonally. PMID- 7797597 TI - DNA repair synthesis following irradiation with 254-nm and 312-nm ultraviolet light is not diminished in fibroblasts from patients with dysplastic nevus syndrome. AB - The DNA excision repair capacity of 23 primary fibroblast lines from patients with dysplastic nevus syndrome was investigated and DNA repair synthesis ("unscheduled DNA synthesis") was determined after UV exposure. Seventeen fibroblast lines from normal donors served as controls. The dose/response experiments included up to ten dose levels and two wavelength ranges: UV-C (using a low-pressure mercury lamp emitting predominantly 254-nm light) and UV-B (artificial "sunlamp" radiation centering around 312-nm light). For each dose level, silver grains over fibroblast nuclei were counted by visual inspection. Twelve cell lines were also evaluated for both UV wavelength ranges using a new semi-automatic image analyzing system. This system included components for rapid sequential identification of both fibroblast nuclei and silver grains sited above them. Silver grains over 100 nuclei were determined for each UV dose level. Dose/response curves were established and analyzed by linear regression. As a quantitative term for assessing DNA excision repair capacity of a cell line we calculated the linear increase (G0) in the number of grains per nucleus, when the UV dose was multiplied by the factor e (i.e. 2.72). The sensitivity of grain detection and resolution of overlapping grains was approximately threefold better in visual than in automatic counting, especially when there were more than 70 grains over nuclei. The time required for visual counting, however, was tenfold that of automatic counting. The variance-weighted mean G0v.w of all fibroblast lines from patients with dysplastic nevus syndrome was found to be 79.1 (+/- 1.8- grains/nucleus, that of fibroblast lines from normal donors was 74.2 (+/- 1.7) grains/nucleus. This difference revealed a slightly better repair capability for cell lines from patients but was at the borderline of detection and, therefore, should not be overinterpreted. From the experimental accuracy achieved by determination of the variance-weighted means of the two groups, we would have been able to detect a difference of 7 and more grains [> 2 x (sigma normal+sigma patients)]. The variance-weighted mean G0v.w of all fibroblast lines from patients with dysplastic nevus syndrome was found to be 76.4 (+/- 1.4) grains/nucleus, whereas that of fibroblast lines from normal donors was only 66.6 (+/- 1.8) grains/nucleus. This difference was statistically significant and, contrary to expectation, revealed better, not worse post-UV DNA repair capability in cell lines from patients that in those from normal donors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7797598 TI - The effect of stem-cell factor, interleukin-3 and erythropoietin on in vitro erythropoiesis in myelodysplastic syndromes. AB - An inherent defect of erythroid differentiation at the colony-forming unit blast (CFU-blast) compartment and (or) an impaired response of early erythroid progenitors (BFU-E) to growth stimulation are both considered to contribute to anemia in myelodysplastic syndromes (MDS). With the intention of improving survival and growth of early erythroid progenitors we investigated the effect of stem-cell factor (SCF) and interleukin-3 (IL-3) alone and in combination with erythropoietin, on the in vitro erythropoiesis of 13 patients with MDS and of three normal controls. SCF and IL-3 alone did not promote erythroid colony growth in MDS, while 3 cases responded to erythropoietin alone. In each of these, BFU-E colony growth could be increased by SCF, which was also found in all normal bone marrows. Altogether 6 cases showed a significant enhancement of BFU-E colony numbers by the combination of SCF and erythropoietin as compared to erythropoietin alone (P = 0.036). Out of the 6 responding cases, 5 belonged to the FAB-classified subgroups refractory anemia (RA) and refractory anemia with ringed sideroblasts (RA/RS) (5/5), while 1 patient was classified as having refractory anemia with excess of blasts (RAEB) (1/4). No patient with refractory anemia with excess of blasts in transformation (RAEB-T) (0/4) responded. In spite of these positive effects, the absolute number of BFU-E colonies remained reduced in all MDS cases when compared to normal controls. IL-3 proved ineffective in increasing the response to erythropoietin in MDS although it increased erythropoietin-induced BFU-E formation in normal controls significantly. We conclude that the striking synergistic effect of SCF and erythropoietin on erythroid colony formation seen with normal bone marrow is conserved in most cases with RA and RA/RS. In RAEB and RAEB-T the intrinsic defect of the erythroid differentiation pathway cannot be overcome by SCF. PMID- 7797599 TI - Effects of pravastatin, a hydroxymethylglutaryl-CoA reductase inhibitor, on two human tumour cell lines. AB - Competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase are currently used to treat patients with hypercholesterolaemia. These inhibitors affect not only cholesterol biosynthesis, but also the production of non-steroidal mevalonate derivatives, that are involved in a number of growth regulatory processes. As a consequence, their potential use as anticancer drugs has been suggested. In order to examine long-term effects of this potential therapeutic approach, we cultivated the gastric carcinoma cell line, EPG85-257, and the breast tumour cell line, MDA-MB231, in the presence of increasing concentrations of the HMG-CoA reductase inhibitor, pravastatin. For both cell lines, this procedure led to the selection of resistant variants able to proliferate in more than 1000 microM inhibitor. By competitive reverse transcriptase/polymerase chain reaction assay (cRT-PCR), the expression of the mRNA for two key proteins of cellular cholesterol metabolism, HMG-CoA reductase and low-density lipoprotein (LDL) receptor, were analysed in sensitive and resistant cells. Despite similar growth rates, MDA-MB231 cells expressed approximately four times more HMG-CoA reductase mRNA than EPG85-257 cells and over 30 times more LDL receptor mRNA. Both mRNA species were coordinately regulated in the parental and in the pravastatin-resistant variant cells. Expression was highly stimulated (3- to 4-fold for the HMG-CoA reductase and 2- to 3-fold for the LDL receptor) in the resistant variants when cultured in lipoprotein-deficient medium in the presence of 1000 microM pravastatin. Immunocytological analysis of the expression of the HMG-CoA reductase and LDL receptor protein were in accordance with the data on specific mRNA expression obtained by cRT-PCR. Southern blot analysis revealed a 1.5-fold amplification of the HMG-CoA reductase gene in resistant MDA-MB231 cells, but not in the resistant EPG85-257 variant. Our data provide evidence for resistance mechanisms to pravastatin that are independent of the amplification of the HMG-CoA reductase gene. By analogy to the cell-culture models employed in this study, it is conceivable that similar mechanisms might occur in human tumour cells in vivo during long-term treatment with HMG-CoA reductase inhibitors. This might limit their application as chemotherapeutic anticancer agents. PMID- 7797600 TI - Alkylphosphocholine-induced production of nitric oxide and tumor necrosis factor alpha by U 937 cells. AB - The human histiocytic cell line U 937, which expresses a number of monocyte markers and properties, was investigated with regard to its ability to be activated for NO and tumor necrosis factor (TNF) release after treatment with alkylphosphocholines (APC) and APC liposomes. Using APC multilamellar vesicles (MLV) a clear dose-dependent increase of NO production could be demonstrated for U 937 cells, whereas the corresponding soluble substances had no effect. The time course of NO release was characterised by a peak between 2 h and 12 h and a strong decrease after 24 h. LPS caused no NO release nor the production of TNF in U 937 cells. The simultaneous incubation of the cells with lipopolysaccharide and APC or APC-MLV, led to a strong increase in TNF production. Closer investigation of the time sequence of this synergistic effect demonstrated that cells, that had first been treated with hexadecylphosphocholine (HPC)-MLV and 4 h later with lipopolysaccharide secreted significantly more TNF into the supernatants than in the experiment where both substances were added simultaneously. From these results it was concluded that APC-MLV are possibly able to act as a primer in the process of lipopolysaccharide mediated TNF induction. Furthermore, a positive influence of phorbol 12-myristate 13-acetate (PMA) on the ability of U 937 cells to produce TNF following a treatment with HPC or HPC-MLV could be observed. PMA pretreated cells were shown to release much more TNF compared to control cells, which led to the supposition that the immunomodifying activity of APC becomes effective only in more highly differentiated cell types. PMID- 7797601 TI - Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. AB - The bcl-2 protooncogene was initially discovered at the t(14;18) chromosomal breakpoint in follicular lymphomas. It has been demonstrated that bcl-2 protein (Bcl-2) expression blocks apoptosis and plays an important role in cell development and maturation. In the present study, Bcl-2 expression was immunohistochemically examined in 103 cases of gastric carcinoma, as well as 64 cases of non-carcinous gastric mucosa, and its correlation with apoptosis, cell proliferation and p53 immunoreactivity was investigated. Bcl-2 was detected in 18.0% of differentiated-type gastric carcinomas (9 of 50) and 7.5% of the undifferentiated type (4 of 53). In adjacent intestinal metaplastic gastric epithelium, the incidence of Bcl-2 positivity in the incomplete type (21/23, 91.3%) was significantly higher than in the complete type (23/41, 56.1%) (P < 0.04). Double immunostaining for Bcl-2 and Ki-67 clearly revealed the majority of Bcl-2-positive cancer cells to be in a nonproliferating state, although some cancer cells expressed both proteins together. Statistical assessment demonstrated that the average Ki-67 labeling index and apoptotic labeling index in Bcl-2-positive foci were significantly lower than in Bcl-2-negative foci (P < 0.0001, P < 0.0003). In addition, a significant dissociation between Bcl-2 and p53 immunoreactivity was found in cancer tissues. These results indicate that aberrant Bcl-2 expression in gastric carcinomas possibly originates from intestinal metaplastic epithelium, and suggest a possible role in tumor development and growth. PMID- 7797602 TI - Efficacy of famotidine in patients with acute gastric mucosal injury after continuous infusion of cisplatin plus vindesine. AB - The effect of famotidine (H2 blocker) on the gastroduodenal mucosal injury induced by chemotherapy in non-small-cell lung cancer patients was prospectively evaluated from the clinical and endoscopic findings obtained in a randomized double-blind study. The patients, who were administered cisplatin (25 mg/m2/day, continuous infusion, days 1-5) and vindesine (3 mg/m2, bolus, days 1 and 8), were randomized into two groups, those administered famotidine (40 mg/day, oral) and those administered the placebo. The patients were examined by gastroduodenoscopy within 7 days before and after chemotherapy. There were 27 patients in the famotidine group and 28 patients in the placebo group. The gastric mucosal score after chemotherapy was significantly lower in the famotidine group than in the placebo group (P < 0.01), and in the 42 patients without symptoms than in the 13 patients (placebo group: 8, famotidine group: 5) with upper gastrointestinal symptoms (P < 0.01). The pH of the gastric juice after the chemotherapy significantly decreased in the placebo group (P < 0.05), and was significantly lower in the placebo group than in the famotidine group (P = 0.01). The co administration of famotidine was effective in the prevention and control of chemotherapy-induced gastric mucosal injury. PMID- 7797603 TI - P53 accumulation and proliferating-cell nuclear antigen expression in human lung cancer. AB - Mutations in the p53 gene are currently the commonest genetic alterations in human malignant tumors, including non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Alterations of the protein induced by gene mutations enables the mutant protein to become more stable, resulting in the accumulation of P53 in quantities detectable by immunohistochemistry. Although previous studies document the accumulation of P53 in lung cancer, there is little information regarding the usual frequency of accumulation based on a comprehensive number of lung tumors. A total of 328 paraffin-embedded lung carcinoma specimens were analyzed for P53 accumulation and for the expression of the proliferating-cell nuclear antigen (PCNA) by standard immunohistochemistry. Among 49 SCLC, 35% were positive for p53 and 51% were positive for PCNA. Out of 279 NSCLC, 43% showed a positive P53 immunoreaction and 72% displayed detectable amounts of PCNA. In squamous-cell carcinomas a statistically significant increased accumulation of P53 was found compared to adenocarcinomas (P = 0.001). Among the 233 PCNA-positive tumors the relative number of P53-positive specimens was higher compared to the total number of tumors. Since immunohistochemical investigations should contribute to the improvement of the clinical diagnosis and treatment or give information on the prognosis, we conclude from our results that it seems to be legitimate to assess the P53 status exclusively in the specimens positive for PCNA. Immunohistochemical investigations under consideration of the PCNA status yielded good and fast recognition of p53 mutations leading to intracellular P53 protein accumulation. PMID- 7797605 TI - High-dose chemotherapy with blood stem-cell transplantation in the treatment of solid tumors and hematological malignancies. A one-day course in the continuing education program organized by the Tumor Center Heidelberg/Mannheim, February 1995. PMID- 7797604 TI - Formestane: an effective first-line endocrine treatment for advanced breast cancer. AB - Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies. PMID- 7797606 TI - Structure-activity study on antiulcer agents using Wiener's topological index and molecular connectivity index. AB - The relationship of Wiener's topological index and molecular connectivity index with antiulcer activity of a series of 4-substituted-2-guanidino thiazole analogs has been investigated. The values of Wiener's topological index and molecular connectivity index of 128 compounds were computed and active ranges were identified. The activity assigned to each analog using these topological descriptors was subsequently compared with the reported in vitro and in vivo activities against gastric hydrogen-potassium stimulated adenosine triphosphatase (H+K(+)-ATPase) enzyme. Predictions with an accuracy of the order of approximately 89% were observed with regard to in vivo activity using these topological indices. PMID- 7797607 TI - Structure-activity study on antiinflammatory pyrazole carboxylic acid hydrazide analogs using molecular connectivity indices. AB - The relationship between molecular connectivity indices and the antiinflammatory activity of a series of pyrazole carboxylic acid hydrazide analogs has been investigated. The values of molecular connectivity index, valence molecular connectivity index, and a modified index, termed as atomic molecular connectivity index for 76 compounds, were computed and active ranges were identified. Each compound was assigned an activity which was subsequently compared with the reported activity against lipoxygenase enzyme. Predictions with a degree of accuracy above 80% were observed using the valence molecular connectivity index. PMID- 7797608 TI - Electrostatic potential derived charges for enzyme cofactors: methods, correlations, and scaling for organic cofactors. AB - The correlations between electrostatic potential (ESP) derived atomic charges for a wide range of different quantum mechanical approaches and basis sets have been investigated for both small and large organic structures including several enzyme cofactors. The previously observed linear correlation between ESP charges calculated by different approaches has been verified to extend to many different basis sets and procedures including effective core potential (ECP) basis sets, density functional theory (DFT) approaches, a hybrid Hartree-Fock (HF)/DFT approach, and inclusion of electron correlation corrections. Above a threshold level of complexity, most procedures and basis sets give results that correlate very well (linear correlation coefficients > 0.99), including several procedures that have reasonable computational costs for large molecules. These procedures have been used to calculate ESP charges for five different types and forms of enzyme cofactors: biotin, pyridoxal-5'-phosphate, pyridoxamine-5'-phosphate, and the flavin mononucleotide in two different oxidation states. PMID- 7797609 TI - Bioactive conformations of small peptides: a method for selection of candidates based on conformations of active and inactive analogues and its application to muramyl dipeptide. AB - A method has been developed that selects a subset of candidates for the bioactive conformation based on the comparison of conformation clusters of the active and inactive ligands. Those conformations of the active ligand that cannot be reached by inactive ligands in spatially presenting preselected "target" atoms (conformations "unique" to the active ligand) are extracted. The method is applied to muramyl dipeptide (MDP); the selection of candidates was performed using two of its diastereomers that have no immunostimulative properties. A third diastereomer and a rigidified analogue, both inactive, and the protein-bound conformation of a related peptidoglycan containing the MurNAc-L-Ala-D-Glu sequence are used as test cases; the latter was found to be most similar to one member of the set of unique conformations of MDP. PMID- 7797610 TI - Eicosanoid production by rat cerebral endothelial cells: stimulation by lipopolysaccharide, interleukin-1 and interleukin-6. AB - The capacity of rat cerebral endothelial cells (RCEC) to form eicosanoids was determined after incubation with 14C-labelled arachidonic acid. Prostaglandin E2 (PGE2) was the main metabolite formed by RCEC and was responsible for 54% of the total amount of eicosanoids produced. In contrast, in primary cultures of rat aorta endothelial cells, 32% of the amount of prostaglandins was 6-keto-PGF1 alpha). RCEC treated with 50 ng/ml LPS for 24 h responded with an augmented PGE2 synthesis and 6-keto-PGF1 alpha of 3.4-fold and 2.2-fold, respectively. Cultures treated with IL-1 beta (50 ng/ml) for 3 h showed a stimulation of the release of PGE2 and 6-keto-PGF1 alpha of 2.5- and 4.5-fold, respectively, and 2.0-fold and 2.3-fold, respectively, after IL-6 (50 ng/ml) incubation for 3 h. PGE2 is the main eicosanoid formed by RCEC in response to inflammatory agents, suggesting an important role of the cerebral endothelial cells in the transduction of an inflammatory response in the central nervous system. PMID- 7797611 TI - Psychological stress and immunological responsiveness in normally cycling, follicular-stage women. AB - Nineteen women in the follicular stage of their menstrual cycles were assessed for immunological responsiveness to a 50-min series of three psychological tasks which reliably elicit cardiovascular and neuroendocrine stress responses. Ten follicular-stage women not subjected to stress served as controls. Stress decreased lymphocyte responsiveness to PHA and PWM, percent of CD4+ cells and the ratio of CD4+/CD8+ cells. Conversely, stress increased natural killer cell number and cytolytic activity, white blood cell, lymphocyte, T and B cell count. Except for natural killer cell number, none of these changes was exhibited by controls. Most of these stress responses are similar to those reported for men and form the basis for a continuing study of the effects of reproductive hormones and stress on cardiovascular and immunological function in women. PMID- 7797612 TI - TAP2 polymorphisms in Australian multiple sclerosis patients. AB - Polymorphism of the TAP2 gene locus, situated approximately 150 kb centromeric to the MHC class II loci HLA-DR, DQ was examined in 100 Australian patients with relapsing/remitting multiple sclerosis (MS), in 100 random controls and in 37 selected HLA-DRB1*1501-positive controls. The results were correlated with HLA class I and class II phenotypes. TAP2 encodes a protein involved in the transport and presentation of antigenic peptides by MHC class I molecules and hence is a candidate locus for a putative MS susceptibility gene either through functional interactions with class I alleles or as an explanation, via linkage disequilibrium (LD), for the known association between MS and the alleles DRB1*1501, DQA1*0102, DQB1*0602. Strong LD was found between the allele TAP2*01 and DRB1*1501 in both the MS and control populations. The MS-associated haplotype can therefore be extended to DRB1*1501, DQA1*0102, DQB1*0602, TAP2*01, and the putative gene locus could reside on the centromeric side of DQ. TAP2 typing, however, could not explain the DRB1*1501, DQA1*0102, DQB1*0602-negative patients in whom, interestingly, the frequency of TAP2*01 was decreased compared to controls. The results of this study exclude TAP2 as a locus for a necessary MS/MHC gene but indicate that an MS gene carried by the DRB1*1501, DQA1*0102, DQB1*0602 haplotype could reside centromeric of DQ. PMID- 7797613 TI - Postmortem delay effects on neuroglial cells and brain macrophages from Lewis rats with acute experimental allergic encephalomyelitis: an immunohistochemical and cytochemical study. AB - The effects of increasing postmortem delay (PMD) times on morphological, immunological and functional characteristics of various brain cells both in situ and in vitro were studied in postmortem brain tissue derived from rats with acute experimental allergic encephalomyelitis (EAE). A decline of the brain tissue structure was first noted after a PMD of 6 h. Radial glia in the cerebellum were frequently interrupted and retractions artifacts appeared around brain cells. However, even after the longest PMD interval of 18 h the quality of the cell and tissue structure was still good enough for immunohistochemical characterization. Immunohistochemical staining of frozen and fixed rat brain tissue sections resulted in an enhancement of the immunoreactivity after a PMD of 4 h, using a panel of mono and polyclonal antibodies directed against glial fibrillary acidic protein (GFAP), basement membranes (laminin), brain macrophage antigens (ED1 and ED2), and various immunologically important surface molecules, such as major histocompatibility complex (MHC) class II (Ia) antigen (OX6), CR3 complement receptor (ED8), and leukocyte common antigen (OX1). No increase in staining intensities with the ED1, ED8 and OX6 mAbs specific for macrophage antigens could be detected on brain macrophages that were isolated from brain tissue of rats with EAE obtained after various PMD intervals. Irrespective of the PMD interval, viable astrocyte cell cultures were obtained with comparable staining intensities for GFAP. These cultured astrocytes were capable of ingesting Latex beads and were highly proliferative as measured by BrdU uptake, at all investigated PMDs. Thus, even after long PMD intervals, brain material can be used successfully. Other data suggest that the situation is similar to human brain material, even though the PMD times may be somewhat different. PMID- 7797614 TI - Molecular cloning of the coding sequence of an interleukin-2 receptor alpha subunit cDNA in murine brain. AB - Interleukin-2 (IL-2) has various trophic and neuromodulatory actions in the mammalian central nervous system (CNS). The interleukin-2 receptor alpha (IL-2R alpha) is an accessory subunit of the IL-2 receptor heterotrimer complex which is essential for 'high' affinity IL-2 binding. Although an IL-2R alpha (or IL-2R alpha-like) epitope has been localized in brain by immunohistocytochemistry, it was unknown whether the IL-2R alpha subunit expressed in brain was derived from the same or a different gene than the lymphocyte IL-2R alpha. Therefore, in the present study, the cDNA comprising the full length coding region was cloned and sequenced from saline-perfused forebrain. The brain IL-2R alpha cDNA was found to be 100% homologous with the corresponding lymphocyte IL-2R alpha cDNA sequence. IL-2R alpha mRNA was expressed at very low levels in saline-perfused forebrain of non-challenged BALB/c mice as well as in saline-perfused forebrain from severe combined immunodeficiency (SCID) mice. The present data, demonstrating IL-2R alpha gene expression in both well-perfused normal and SCID mouse forebrain from which no CD3 gamma gene expression was detected by PCR, provides evidence that the IL-2R alpha clones isolated are from resident brain cells and not from blood lymphocytes (e.g. T lymphocytes). Thus, these findings demonstrate that the protein coding sequence of the mouse brain IL-2R alpha is derived from the same gene coding sequence as the lymphocyte IL-2R alpha, and indicate that previously reported differences in the size of their respective mRNA transcripts appear to be due to differences in untranslated regions. PMID- 7797615 TI - Sigma-1 receptors modulate functional activity of rat splenocytes. AB - Neuroleptics, opiates, and cocaine are commonly prescribed for or abused by humans. Although primarily used for their actions at other receptors in brain, these compounds also act at sigma receptors. We have previously identified sigma 1 receptors on human peripheral blood leukocytes and rat spleen, and in the present study we demonstrate a correlation between the pharmacology of these receptors and the ability of drugs to suppress concanavalin A-induced splenocyte proliferation. These results support the hypothesis that sigma-1 receptors regulate functional activities of immune cells, and suggest that sigma agonists may cause changes in immune competence in vivo. PMID- 7797616 TI - Genetic analysis of susceptibility to Theiler's murine encephalomyelitis virus induced demyelinating disease in the SWR strain. AB - SWR/J mice are susceptible to immune-mediated central (CNS) demyelination following infection by Theiler's murine encephalomyelitis virus (TMEV). SWR/J susceptibility is genetically dominant, when outcrossed to resistant H-2b strains. Non-H-2 differences between C57BL/6 and C57L/J (both H-2b) alter effects of 'susceptibility' genes, especially H-2q, from SWR/J. Genetic analysis of differential susceptibility to demyelination between SWR/J and C57L/J indicates that one copy of H-2q is sufficient for disease, and that SWR/J mice carry a non H-2 gene which can lead to disease in the absence of H-2q. Differential susceptibility between SWR/J and C57BL/6 is determined by a single non-H-2 locus, which may or may not be the same as that differing between SWR/J and C57L/J. PMID- 7797617 TI - The relationship of TAP1 and TAP2 dimorphisms to multiple sclerosis susceptibility. AB - Transporters associated with antigen processing and presentation (TAP1 and TAP2) have been considered candidate genes in MS susceptibility based on evidence from experimental animal models confirming antigenic peptide selection by transporter polymorphisms and by the proximity of these transporter genes to the DR- and DQ associated alleles known to confer disease risk in man. We report here an association study examining the influence of TAP gene polymorphisms on MS susceptibility in a Canadian patient population. Our results do not support a role for the five polymorphisms examined in the etiology of this disease. PMID- 7797618 TI - beta-Amyloid(25-35) induces the production of interleukin-8 from human monocytes. AB - In an effort to unravel some of the cellular actions of beta-amyloid protein (A beta), we investigated its effects on interleukin-8 (IL-8) production from human monocytes. Supernatants harvested from cultured monocytes stimulated with the neurotoxic fragment 25-35 of beta-amyloid [A beta(25-35)] contained significant amounts of IL-8. Northern blot analysis demonstrated that A beta(25-35) also induced IL-8 mRNA accumulation. The effect of A beta(25-35) on IL-8 mRNA accumulation and secretion was not mimicked by a scrambled A beta(25-35) peptide, and was not affected by polymyxin B sulphate, which, on the other hand, almost completely abolished the effect of lipopolysaccharide. Our results uncover a new biological action of beta-amyloid: that of stimulating the production of a chemokine from monocytes. PMID- 7797619 TI - Changes in the expression pattern of blood-brain barrier-associated pericytic aminopeptidase N (pAP N) in the course of acute experimental autoimmune encephalomyelitis. AB - The role of cerebral pericytes in blood-brain barrier (BBB) mechanisms is still a matter of controversy. Because acute experimental autoimmune encephalomyelitis (EAE) is characterized by a transient and focal perturbation of the BBB, we have utilized the model of adoptive transfer EAE to correlate the expression of the pericytic aminopeptidase N (pAP N) with the acute functional state of the BBB. We demonstrate that a significant downregulation of microvascular pAP N expression occurs, and the observed perturbation of the enzymatic BBB complement seems to be a sustained effect which persists even after recovery from clinical disease. At the peak of clinical disease, numerous pAP N expressing invasive cells were detected in white matter of the lumbar spinal cord. Through the use of a panel of different immunocytochemical markers these pAP N-immunopositive cells were characterized as ED 1-positive, most likely hematogenous macrophages. Activated resident microglial cells participate in the EAE-induced inflammatory process to only a minor extent. PMID- 7797620 TI - Arecoline a muscarinic cholinergic agent conditions central pathways that modulate natural killer cell activity. AB - The central nervous system plays an active role in the regulation of the immune system. Modulation of immune activities appears to be in part under the control of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effect of a muscarinic cholinergic agonist, arecoline, which stimulates the secretion of corticotropin-releasing hormone (CRF) and adrenocorticotropic hormone (ACTH) on the immune system. In this report we demonstrate that peripherally administered arecoline or ACTH can increase activity of pre-activated NK cells. Second, we show that central administration of arecoline at a dose too low to alter peripheral events is sufficient to induce a significant increase in the activity of pre-activated natural killer (NK) cells. Finally, we demonstrate by using a Pavlovian conditioning paradigm that the pairing of a novel odor (camphor) with administration of arecoline can be used to alter NK cell activity. Subsequent to the conditioning trial, exposure to the odor alone is sufficient to raise NK cell activity. From these observations, we infer that the pathway(s) that are conditioned reside in sites located within the CNS and the conditioned response is evoked in the peripheral compartment (NK cell activity). PMID- 7797621 TI - Trimethyltin increases interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha mRNA levels in rat hippocampus. AB - Within the central nervous system (CNS), cytokines are though to have active roles in pathophysiological changes seen in various neurological diseases and trauma. The present study was undertaken to examine the early response of pro inflammatory cytokines following exposure to a specific neurotoxicant (trimethyltin; TMT). mRNA levels for interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor (TNF) alpha were measured in the hippocampus of adult male Long-Evans hooded rats following an acute injection of trimethyltin hydroxide (8 mg TMT/kg body weight). At various times following exposure (6 h to 8 days), hippocampal tissues were excised and relative changes in cytokine mRNA levels were assessed by reverse transcription and polymerase chain reaction. IL-1 alpha, IL-6 and TNF alpha mRNA levels in the hippocampus increased within 6 h and remained elevated for 8 days. Quantitative analysis of mRNA transcripts revealed a two-fold increase in both IL-6 and TNF alpha within 6 h and a continued elevation of TNF alpha to 9-fold by 12 h. Within 96 h, glial fibrillary acidic protein (GFAP) mRNA levels were elevated in the hippocampus. Histological examination showed sparse individual neuronal necrosis at this time in both the pyramidal and granule cell regions with no increase in astrocyte GFAP immunoreactivity. However, an early, 24 h, response of microglial cells was indicated by increased lectin binding. This morphological profile progressed over time to a profound neuronal loss in the CA3-4 granule cell layer and marked astrocyte hypertrophy. The onset of pro-inflammatory cytokine mRNA expression appears to be temporally associated with histological evidence of elevated microglia in the hippocampus. It is proposed that microglia and pro-inflammatory cytokines play a modulatory role in the early stages of TMT-induced neurotoxicity. PMID- 7797622 TI - Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DR beta 1 chain in multiple sclerosis. AB - The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR beta 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR beta 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1*1501 allele and through linkage also of the DRB1*1501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB1*1501/DRB1*0400 or DR beta 1Ala71+ His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1Phe47+, DR beta 1Asp70+ and DR beta 1Thr140+, DQ alpha 1Phe25+, DQ alpha 1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)-DQ alpha 1Phe25+ and DR beta 1(Ser13+)-DQ alpha 1Phe25+ haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove. PMID- 7797623 TI - Lytic effector cell activity and major depressive disorder in patients with breast cancer: a prospective study. AB - The study examined lymphokine-activated killer cell (LAK) and natural killer (NK) cell activity in breast cancer patients prior to surgery as compared to effector cell lysis in patients with non-malignant breast tumors, further in connection with lifetime diagnosis of major depression, severity of current depression, anxiety and coping styles. Follow up studies covered a period of 6 and 12 months. Prior to surgery, life time diagnosis of major depressive disorder, trait anxiety and coping styles did not discriminate patients as far as effector cell lysis is concerned. LAK activity but not NK activity was reduced in patients with actual depressive symptoms (P < 0.01) and high state anxiety (P < 0.05). These findings support the hypothesis that LAK activity is a state marker of actually existing depression and anxiety prior to surgery. Affective rather than coping measures showed significant differences in LAK activity. For LAK activity, 1 year after surgery the only predicting factors were Tamoxifen therapy and chemotherapy. PMID- 7797624 TI - Increased deposition of extracellular matrix components in the thymus gland of MDX mouse: correlation with the muscular lesion. AB - The present work describes the expression of extracellular proteins in the thymus and skeletal muscle of the X-linked dystrophic MDX mouse which corresponds to an experimental model for the human disease Duchenne muscular dystrophy. MDX dystrophic mice showed marked alterations in the thymic cytoarchitecture including cortical atrophy that was paralleled by denser epithelial cell network with intense immunolabelling for cytokeratins pair 8/18 and increased vascularization assessed with monoclonal antibody anti-desmin. Consistent augmentation of intrathymic extracellular matrix components (ECM) was observed especially at weaning and by the onset of disease. Interestingly, the amount of ECM elements in the gastrocnemius muscle of MDX wild-type dystrophic mice also showed a prominent difference as compared to age-matched non-dystrophic BALB/cAn animals. A marked but uneven overdeposition of reticulin and collagen fibres (type I, type IV), laminin and fibronectin were often present in the skeletal muscle of dystrophic mice, mostly around lesioned fibres. Alterations in both organs positively correlated with the degree of dystrophy thus suggesting that similar stimuli may be enhancing ECM production in both thymus and skeletal muscle. Although the thymus gland might not be directly involved in the development of the murine X-linked muscular dystrophy, it should be considered as a further target in this disease. PMID- 7797626 TI - Electroencephalography of the elderly. PMID- 7797625 TI - Functional role and sequence analysis of a lymphocyte orphan opioid receptor. AB - Pharmacological evidence indicates that lymphocytes express opioid receptors, but this finding has been questioned. By DNA sequencing of reverse transcription polymerase chain reaction products, we have found that mouse lymphocytes express mRNA encoding an orphan opioid receptor. These mRNA transcripts were detected in the CD4+, CD8+, and CD4- CD8- lymphocyte subpopulations. Northern blot analysis confirmed that splenic lymphocytes express a 1.5-kb orphan opioid receptor mRNA. Fifteen bases encoding Tyr71-Arg75 in the first intracellular loop are alternatively spliced, suggesting that orphan opioid receptor mRNA encodes two receptor subtypes. Treatment of lipopolysaccharide-stimulated lymphocytes with orphan opioid receptor antisense oligonucleotides suppressed polyclonal IgG and IgM production by 50%. Our results provide direct evidence that lymphocytes express an opioid-like receptor gene, and suggest that this receptor plays a functional role in immunocompetence. PMID- 7797627 TI - Evoked potentials in the elderly. AB - Evoked potentials (EPs) provide a quantitative measure of function rather than structure of certain pathways and processes within the nervous system. These systems and processes change with maturation and senescence. There are minimal somatosensory EPs changes after maturation until senescence. There are moderate changes in interpeak latencies, but few changes in the central conduction time (CCT). Brainstem auditory EPs change minimally with aging, with the CCT prolonging by 1-4 ms/year, possibly in a gender-dependent fashion. Latencies of visual EPs prolong by 2-4 ms/decade after age 40 years. The P300 amplitude, latency, and distribution all change with age. An understanding of the characteristics of EPs in aging humans is essential to accurate clinical interpretation of these studies. PMID- 7797629 TI - Arousal fluctuations in non-rapid eye movement parasomnias: the role of cyclic alternating pattern as a measure of sleep instability. AB - Some non-rapid eye movement (NREM) parasomnias, such as sleep-walking (SW), sleep terror (ST) and, in some aspects, sleep enuresis (SE), are considered "arousal disorders" without significant polysomnographic changes in classic sleep macrostructure. The aim of our study was to evaluate sleep microstructure and oscillations of arousal level by cyclic alternating pattern (CAP) scoring in some NREM parasomnias. Nocturnal polysomnography and videotape recording was used to study 21 patients with motor and behavioral phenomena during sleep: 13 in Group A (seven SW, six ST) with delta sleep-related episodes, eight in Group B with other parasomnias (six sleep bruxism and two SE), and six healthy controls. Classic sleep macrostructural parameters were no different in the parasomniacs and controls. Compared with the controls, our patients' sleep microstructure, scored by CAP analysis, showed increases in CAP rate (a measure of NREM instability with high level of arousal oscillation), in number of the CAP cycles, and in arousals with EEG synchronization, the increases being more significant in Group A than in Group B. An increase in sleep instability and in arousal oscillation seems to be a typical microstructural feature of delta sleep-related parasomnias and probably plays a role in triggering abnormal motor episodes during sleep in these patients. PMID- 7797628 TI - Sleep and sleep disorders in older adults. AB - Complaints of sleep disturbance increase with age. Objective sleep assessments using polysomnography reveal sleep impairments (increased wakefulness and arousal from sleep; decreased slow wave sleep) even in healthy seniors. Both polysomnographic sleep and subjective sleep worsen in the presence of health impairments related to drug use, pain, cardiovascular disease, diabetes, depression, or other emotional disorders. In addition to normal aging and chronic disease, sleep complaints can also result from poor sleep habits, specific occult disorders during sleep, or some combination of these factors. Occult disorders include sleep apnea syndrome, periodic leg movements, and restless legs syndrome during sleep. Diagnosis and treatment of these and other sleep disorders is discussed. Both pharmacological and nonpharmacological treatments are considered, with an emphasis on behavioral and educative treatment approaches. PMID- 7797630 TI - Brain processing of stimulus deviance during slow-wave and paradoxical sleep: a study of human auditory evoked responses using the oddball paradigm. AB - Auditory evoked potentials (AEPs) to frequent (90%) and deviant (10%) tones were recorded during both wakefulness and all-night sleep in eight drug-free volunteers. During presleep waking (10:00-11:00 p.m.), deviant stimuli elicited, in all subjects, a prominent "P300" wave of parieto-central topography, culminating at 344 ms (average), which was absent in response to frequent tones. This "presleep P300" was delayed and reduced relative to values obtained during full wakefulness (3:00-7:00 p.m.) in a control group. Passage from waking to sleep stage I was characterized by a progressive attenuation and delay of the P300 wave in response to deviant stimuli, without major changes in AEP morphology as compared to the waking state. Thus, in terms of cognitive evoked potentials (EPs), sleep stage I appeared more as a "weak" state of wakefulness than a true phase of sleep. During sleep stages II, III, and IV, both frequent and deviant tones evoked AEPs that closely resembled K-complexes. Responses to rare stimuli were four-to-five times larger than those to frequent tones, this likely being the result of K-complex habituation to monotonous stimuli. During paradoxical sleep (PS), AEP morphology again became comparable to that of wakefulness. Notably, a "P3" wave with similar topography as the waking P300 appeared in response to deviant stimuli exclusively. Thus, even though the brain seems able to detect stimulus deviance during all sleep stages, only during stage I and PS were the electrophysiological counterparts of deviance detection comparable to those of the waking state. Our results support the view that PS is not a state of "sensory isolation"; failure to respond to external stimuli during this stage may depend upon mechanisms occurring only after the sensory input has undergone cognitive analysis. PMID- 7797631 TI - Auditory evoked responses in children during hypothermic cardiopulmonary bypass: report of cases. AB - Variations in core temperature and cerebral blood flow during open heart surgery may affect auditory brainstem responses (ABRs) and middle latency responses (MLRs) in both adults and children. We documented the changes in ABRs of two infants (ages 3 and 11 weeks, respectively) with variations in core temperature during hypothermic cardiopulmonary bypass and total circulatory arrest and compared them with those of a 19-year-old adult. Changes in MLRs that occurred in association with reductions in cerebral blood flow as monitored by transcranial Doppler are also reported in a 6-year-old child. With the reductions in temperature in both infants and the young adult, ABR latencies increased and amplitudes decreased. Effects of hypothermia on ABR latencies were completely reversed by rewarming. MLR amplitudes were transiently reduced during periods of normothermic hypoperfusion. Hypothermia partially prevented these changes, and normoperfusion after rewarming recovered MLRs. Monitoring ABRs and MLRs may be a useful technique for assessment of brain function during hypothermic cardiopulmonary bypass in children and infants. PMID- 7797632 TI - Auditory evoked magnetic fields to tones and pseudowords in healthy children and adults. AB - Neuromagnetic responses to tones and pseudowords were measured with a 24-channel magnetometer in nine adults and in 23 children, the latter aged 0.3-15 years. Both stimulus types elicited substantially similar responses in all subjects. At 0.9-s interstimulus interval (ISI), the adult response was a stable P1m-N1m-P2m N2m sequence peaking at 50, 100, 200, and 250 ms, respectively. A biphasic P1m N1,2m response with peaks at 100 and 260 ms occurred in children up to 12 years of age. At longer ISIs (1.2-2.4 s), an adult-type N1m response appeared in most children. N1m amplitude suppression at short ISIs was stronger in children than in adults and may reflect a longer refractory period of the N1 generator neurons during early childhood than later in life. Peak latencies of P1m, N1m, and N2m decreased with age, most rapidly < 7 years of age. All deflections originated in nearby cortical areas within the posterior sylvian fissure, and may serve as functional landmarks for that anatomic area. PMID- 7797634 TI - Technology and equipment review. Quantitative sensory testing systems. PMID- 7797633 TI - P300 assessment of chronic fatigue syndrome. AB - The P3(00) event-related brain potential (ERP) was elicited with an auditory tone discrimination paradigm in 25 patients diagnosed with chronic fatigue syndrome (CFS) and 25 matched normal control subjects. Target stimulus probability was varied systematically (0.20, 0.50, 0.80) in different task conditions. No differences between the CFS and control subjects were found for either P3 amplitude or latency. No group effects were observed for the N1, P2, and N2 components. Despite the attentional and immediate memory deficits reported in CFS, the P3 ERP from auditory stimuli does not reliably discriminate CFS from matched control subjects. PMID- 7797635 TI - Regarding "Sounds trigger spikes in the Landau-Kleffner syndrome" by R. Paetau. PMID- 7797636 TI - Typicality range deficit in schizophrenics' recognition of emotion in faces. AB - Severity of thought disorder in schizophrenics was assessed by a task that involved recognition of joy and shame expression, with the expressions varied for typicality of the emotion category. Accuracy, typicality rating, and reaction time were measured in schizophrenic patients who were high or low on Whitaker's Index of Schizophrenic Thinking (WIST) and in depressive and normal controls. All groups had significant variation of typicality ratings for joy (normal typicality range), but the clinical groups had smaller typicality ranges for shame recognition and higher mean typicality ratings than did normals. High WIST schizophrenics were least accurate on low typical shame expressions. Results imply that, for shame recognition, schizophrenic and depressive groups used common categorization (no typicality variation in category members) rather than resemblance categorization. PMID- 7797637 TI - Agreement between patient self-report and clinician rating: concurrence between the BSI and the GAF among psychiatric inpatients. AB - Two rating scales were compared for 200 adult psychiatric inpatients at admission to, and discharge from, the hospital. Patients rated their own psychological symptoms on the Brief Symptom Inventory (BSI), and clinicians rated patients' psychological, social, and occupational functioning on the Global Assessment of Functioning (GAF) Scale. Analyses indicated no significant relationships between symptom distress reported by patients and global functioning rated by clinicians. These findings support previous research that has shown minimal congruence among criterion measures that differ in rating source. PMID- 7797638 TI - Suicidal behavior as related to social support and assertiveness among Swedish and Turkish high school students: a cross-cultural investigation. AB - Among 652 Swedish and 654 Turkish adolescents, the study found that 61 Swedish (9.4%) and 71 Turkish (10.9%) adolescents reported that they had made previous suicide attempts. Previous psychiatric contact, female gender, low perceived family support, and suicide attempts in the family for the Swedish group and suicide attempts in the family, low perceived family support, psychiatric disorder in the family, and previous psychiatric contact variables in the Turkish sample were found to be associated with previous attempts. Low perceived family support, previous suicide attempts, low perceived peer support, female gender, previous psychiatric contact, low positive assertion skills, and a small number of friends for the Swedish; and low perceived family support, previous suicide attempts, low perceived peer support, suicide attempts in the family, and previous psychiatric contact variables for the Turkish group were found to be significant predictors of current suicidal risk. PMID- 7797639 TI - Suicidal ideation in high school students: depression and other correlates. AB - English-Canadian high school students (129 boys, 117 girls) participated in a study of the relationship between suicidal ideation and selected personal variables, stress, and social support. Associations were found between suicidal ideation and the variables of gender, self-esteem, locus of control, depression, drug use, stress, perception of health, family status, academic performance, social support, and anomie. Multiple regression analysis identified depression and alcohol use as best individual predictors among these variables. Semi-partial correlation analyses showed that removal of the effect of depression resulted in a loss of initially significant relationships between suicidal ideation and the other variables except for alcohol use, drug use, and health satisfaction. PMID- 7797640 TI - Validating a multidimensional model of the psychopathology of bulimia nervosa. AB - In a recent preliminary report, a multidimensional model for bulimia nervosa was proposed with latent dimensions body dissatisfaction, restricting behaviors, bulimic behaviors, and affective and personality disorder. It was suggested that body dissatisfaction clearly represented a distinct dimension of the disorder. In the current investigation, we cross-validated the prior results on a larger sample with a different set of variables and tested the fit against alternative models. Subjects were 497 women diagnosed as having bulimia nervosa. We performed a confirmatory factor analysis using the LISREL 7 program. The results supported the fit of the four-dimensional model, but also suggested that self-injurious behaviors may represent additional separate dimensions of the disorder, relatively independent of the affective disturbance. PMID- 7797641 TI - The specificity of sociotropy-autonomy personality dimensions to depression vs. anxiety. AB - Previous cognitive vulnerability studies have identified sociotropy/dependency as a personality characteristic related to depression. We evaluated sociotropy in differential prediction of depression vs. anxiety. Participants (70 females, 42 males) were tested on the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) at two points in time (T1 and T2), separated by an interval of 4 weeks. The Sociotropy-Autonomy Scale (SAS) was administered at T1. Sociotropy was related moderately to the BDI at T1 and T2, but also to the BAI. Autonomy was related to neither. Hierarchical multiple regression analyses found sociotropy to predict anxiety at T2, but not depression. The issue of cognitive vulnerability marker specificity is discussed. PMID- 7797642 TI - Multivariate investigation of anxiety in a psychiatric population. AB - The purpose of the present research was to interrelate dimensions of anxiety in a psychiatric population, based primarily on the conceptual formulation of Templer, Corgiat, and Brooner (1984). Two hundred twenty outpatients served as subjects. The Fear Survey Schedule, State-Trait Anxiety Inventory, Hamilton Anxiety Scale, and a Likert-formated criterial symptom checklist for Generalized Anxiety Disorder (GAD) were employed to derive measures of Severity, Stimulus Specificity, Subjective Component (Cognitive vs. Somatic), Chronicity, and Temporal Constancy (Sometimes vs. Always present). Principal components factor analysis yielded three distinct dimensions of anxiety: Morbidity, Subjective Component, and Chronicity. Clinical and theoretical relevance of these findings are discussed specific to construction of a working model of anxiety, clinical assessment of anxiety response systems, and the feasibility of a dimensional approach to understanding psychopathology. PMID- 7797643 TI - The relationship of religious variables to death depression and death anxiety. AB - The present research explored the relationship of religious variables to death anxiety and death depression in 200 persons from the general population in what is apparently the first study to correlate religious variables with death depression. Persons with lower death depression had greater strength of conviction, greater belief in afterlife, and were less likely to say that the most important aspect of religion is that it offers the possibility of life after death. Persons with less death anxiety were found to have greater strength of conviction. The findings were discussed in relationship to previous research that has suggested that religious belief is associated more closely with death anxiety level than is religious practice. PMID- 7797644 TI - PSM-R: Revised Optimism-Pessimism Scale for the MMPI-2 and MMPI. AB - The Revised Optimism-Pessimism (PSM-R) scale was developed for use with either the MMPI-2 or the MMPI. The scale measures explanatory style on a continuum from optimistic to pessimistic by using 263 MMPI items of the original 298-item Optimism-Pessimism (PSM) scale. These 263 items are common to both the MMPI-2 and MMPI. PSM-R norms are based on a random sample of 1,408 normal adults who also were used for developing norms for the original PSM scale. Reliability estimates (.93 for men; .94 for women) indicate that the PSM-R scale is as accurate as the original PSM scale. PMID- 7797645 TI - The Clinical Anger Scale: preliminary reliability and validity. AB - This article reports preliminary evidence for the development and validation of the Clinical Anger Scale (CAS), an objective self-report instrument designed to measure the syndrome of clinical anger. Factor analysis of the CAS confirmed a unidimensional item structure; reliability analyses also demonstrated adequate internal consistency and test-retest stability for the CAS; other results indicated that the CAS was unrelated to social desirability influences. Additional findings indicated that clinical anger was associated positively with several anger-related concepts (e.g., trait anger, state anger, anger-in, anger out, anger-control) and that the CAS was related in predictable ways to people's psychopathological symptoms, personality traits, and early family environments. Implications for future research and therapeutic assessment with the Clinical Anger Scale are discussed. PMID- 7797646 TI - Reliability and factor structure of the Chinese GHQ-30 for parents with preschool mentally handicapped children. AB - The Chinese version of the General Health Questionnaire (GHQ-30) was administered to 381 parents of preschool mentally handicapped children, along with other instruments that assessed their stress, mental health, coping styles, and care giving patterns. The GHQ-30 was found to have high internal consistency as a scale and high item-total correlations for most of the items. Factor analysis with a four-factor solution showed that four factors were abstracted from the scale, namely, anxiety, depression, interpersonal dysfunctioning, and inadequate coping. It also was found that the factors extracted could be reproduced reliably in two random subsamples and that the factor structure derived from the present sample corresponds to the previously reported data on the dimensionality of the Chinese GHQ-30. PMID- 7797647 TI - Psychometric evaluation of the Social Phobia and Anxiety Inventory in college students. AB - The present study reports on the psychometric properties of the Social Phobia and Anxiety Inventory (SPAI; Turner et al., 1989a) in two nonclinical samples of college undergraduates. Exploratory principal-components analysis with varimax rotation replicated the five-factor solutions reported for the 32-item Social Phobia subscale (SP) in sample 1 (N = 200). Confirmatory factor analyses showed that the five-factor structure of the SP and the two-factor structure of the SPAI were appropriate for the second sample (N = 210) data. Coefficient alpha values were high for all the SP and the SPAI subscales. Furthermore, we examined the relations between the SPAI subscales and measures of social fear and anxiety, social desirability, and general psychopathology. Results support the research use of the SPAI in our undergraduate samples. PMID- 7797648 TI - Social desirability effects on measures of adjustment to university, independence from parents, and self-efficacy. AB - Results of regression analyses on data from 96 first-year undergraduates indicated that social desirability (Jackson and Marlowe-Crowne Social Desirability Scales), particularly scores on the Jackson scale, is related strongly to scores on measures of adjustment (Student Adaptation to College Questionnaire), self-efficacy (Hale-Fibel Generalized Expectation for Success Scale), and independence (Psychological Separation Inventory) from mother, but not from father. In addition, both the Jackson and Marlowe-Crowne scales were correlated highly. Independence from parents and self-efficacy each continued to show a relationship with adjustment to university after social desirability effects were removed. Failure to remove the effect(s) of social desirability from the present measures is likely to lead to inflated estimates of their relation to each other or to other measures. PMID- 7797649 TI - Saccadic tracking test--normal data and reliability. AB - A saccadic tracking test, which involves the scanning of a path guided by the direction of a sequence of arrows, was administered to 102 healthy control subjects. The data show a gender effect and a slight age and education effect. The internal consistency--estimated by Cronbach's alpha--was high, .94. The test promises to be a sensitive estimator of the capacity of a subject to explore a visual display, a skill necessary for a wide range of other test performances. PMID- 7797650 TI - Multivariate discriminant function analysis of neurologic, pain, and psychiatric patients with the MMPI. AB - The ability of the MMPI to classify five well-defined patient groups was investigated (N = 394; control, neurologic, psychiatric, chronic pain, and random). Clinical inspection and discriminant function analyses of basic clinical and research scales could not classify groups correctly, but discriminant function analyses of 37 variables loaded with CNS items (Cripe Neurologic Symptom items) correctly classified the groups with 78% overall accuracy (70% of neurologic, 62% of psychiatric, 81% of pain, 84% of controls, and 100% random). Results indicate that differential diagnosis is not possible with clinical inspection of scales, but complex statistical analysis of the MMPI is potentially useful in diagnosis and decision making. A method for applying the discriminant function analysis to individual cases is provided. PMID- 7797651 TI - Meditation as an adjunct to a happiness enhancement program. AB - This study investigated the impact that meditation has on Fordyce's (1977, 1983) Personal Happiness Enhancement Program (PHEP). Experimental subjects were divided into two groups, both of which received instruction on the PHEP. Subjects in one experimental group were taught a meditation exercise in addition to the PHEP. A control group received no instruction. The Happiness Measure, Psychap Inventory, Beck Depression Inventory, and State-Trait Anxiety Scale were dependent measures. The three (groups) x two (pre-post) mixed ANOVAs with Student Newman-Keuls found that the meditation plus PHEP group significantly improved on all dependent measures over both the PHEP only group and the control group. The PHEP only group improved significantly over the control group on all measures except state anxiety. PMID- 7797652 TI - Anxiety in community-based AIDS caregivers before and after personal construct counseling. AB - Personal construct counseling was provided for voluntary AIDS caregivers based in the community, with the goal of reducing their anxiety levels. Seventy-five caregivers participated in the project, 33 of whom received counseling. They were interviewed on three occasions--before, immediately after, and 3 months after counseling. Their responses to an open-ended question were subjected to six subscales of a content analysis scale in order to measure levels of anxiety from six different sources. At time 2, the anxiety of the counseled caregivers was significantly less than that of those not counseled, specifically their anxiety about bodily mutilation and guilt. These differences were not sustained at time 3 because the anxiety of those not counseled dropped. Some criticisms of the project are examined before the meaning of these findings for meeting the mental health needs of AIDS caregivers is discussed. PMID- 7797653 TI - Treatment utility of the sociotropy/autonomy distinction: implications for cognitive therapy. AB - The treatment utility of the Sociotropy/Autonomy Scale was evaluated by matching or mismatching subjects to either individual or group cognitive therapy according to their dominant personality dimension. Both groups of subjects obtained statistically significant, but equivalent, reductions in depression. Consistent with Beck's (1983) interactional model, tests of clinical significance indicated a higher proportion of matched subjects who displayed marked improvement at follow-up. Implications for cognitive therapy and further research on the assessment of personality dimensions relevant to depression are discussed. PMID- 7797654 TI - A taxonomy of Rorschach autisms with implications for differential diagnosis among thinking-disordered patients. AB - A tripartite taxonomy of perceptual-cognitive errors on the Rorschach, abbreviated TRAUT, was reviewed. TRAUT classifies "autisms" as stemming from either an arrant disregard for the blot shapes (HYPO), an inordinate attention to unusual blot areas (HYPER), or an endorsement of counterfactual relationships among blot areas (RELER) included among Exner's Unusual Verbalizations. The scoring of HYPOs and HYPERs and the frequency of their occurrence among thought disordered groups were determined by examining Rorschachs of inpatient schizophrenics, outpatient schizophrenics, borderline personality disorders, and Cluster A personality disorders. Because HYPOs and HYPERs yielded better differential diagnoses than RELERs among these four groups, it was suggested that such percepts should be scored routinely as a screen for thought disorder. PMID- 7797655 TI - Rorschach assessment of the borderline child. AB - After nearly two decades of intensive investigation, adult borderline disorders have achieved wide currency, including a substantial psychological literature. The literature on the diagnostic psychological assessment of borderline children is, in contrast, quite sparse. This paper examines manifestations of childhood borderline conditions on the Rorschach, discusses them in light of current theoretical conceptualizations of adult borderline psychopathology, and explores the relationship between child and adult borderline disorders and the genesis of these conditions. PMID- 7797656 TI - The alcohol paradox: a psychological model. AB - The paradoxical continuation of excessive drinking by chronic alcoholics despite extremely aversive personal deterioration is addressed by a two-factor theory. The theory regards the increasing stereotypy of alcohol-related behaviors as a function of: (a) primary neuropsychological impairments that result from alcohol abuse and (b) secondary fears of catastrophic failure attendant upon brain dysfunction, which leads to acquired aversions to situations that require adaptive behaviors. A schematic quantitative model of this formulation is presented that may be useful to practicing psychologists in explaining perserverative behavior in a variety of brain syndromes. PMID- 7797657 TI - Using and misusing factor analysis to explore group cohesion. AB - Group cohesion is an important construct in understanding the behavior of different types of groups. However, controversy exists about how to conceptualize and measure cohesion, and a central issue is its dimensionality. Consequently, researchers have used factor analysis to examine the structure of the construct of cohesion and measures of it. Our goals in writing this article were to review critically how factor analysis has been used to understand group cohesion, make some recommendations for future factor analytic work, and point out some weaknesses and strengths in using factor analysis to explore cohesion. PMID- 7797658 TI - Color Doppler sonography: anatomic and physiologic assessment of the thyroid. AB - The purpose of this study was to assess the potential application of color Doppler sonography in thyroid imaging. Thyroid nodules and other thyroid pathology detected by color Doppler ultrasound and nuclear scintigraphy were compared in 115 patients. The majority of "cold" nodules demonstrated a peripheral rim of color flow and no internal color flow with color Doppler sonography. A large number of "hot" nodules demonstrated internal color flow. Color Doppler sonography was helpful in delineating nodules in otherwise inhomogeneous glands. We determined that color Doppler cannot reliably distinguish benign from malignant thyroid nodules; fine-needle aspiration biopsy remains the most accurate method in differentiating benign and malignant lesions. We suggest that color Doppler sonography plays only a limited role in the evaluation of nodular thyroid disease at this time. The color Doppler appearance of other thyroid disorders (including toxic multinodular goiter, Graves' disease, and thyroiditis) is discussed. PMID- 7797659 TI - Doppler velocity histogram analysis of hepatocellular carcinoma. AB - To study the characteristics of tumor blood flow, flow profiles from hepatocellular carcinomas (39 profiles) and normal hepatic arteries (23 profiles) were evaluated using velocity histograms obtained with Doppler ultrasound. The histograms were classified into three types: (1) high-peak, (2) flat, and (3) low peak. Characteristically, the low-peak types and the flat types, with flows in opposing directions, were seen only in the tumor vessels. The turbulence in a phantom flow model was of the low-peak type. Spectral analysis revealed that the velocity profile of tumor blood flow was different from that of noncancerous flow and that tumor blood flow was characterized by turbulence. PMID- 7797660 TI - Image-directed color Doppler ultrasonography in the evaluation of superficial solid tumors. AB - Image-directed color Doppler ultrasonography (ICDUS) studies of 86 patients with superficial solid masses yielded significantly lower resistive index (RI) values in acute inflammatory lesions, but no significant difference between the maximum systolic flow velocities (S) of the patient groups with malignant, benign, and acute inflammatory lesions. When analyzed separately, the malignant soft-tissue tumor subgroup was shown to have significantly higher mean RI compared to that of the malignant node subgroup. We conclude that RI may be useful in the differentiation of acute inflammatory masses from other pathological entities. Malignant soft-tissue tumors, especially sarcomas, may have different Doppler features from those of carcinomatous tumors. PMID- 7797661 TI - Image-directed and color Doppler ultrasonography in the diagnosis of postbiopsy arteriovenous fistulas of native kidneys. AB - Using image-directed and color Doppler ultrasonography (ICDUS), we examined 65 patients with single kidney biopsy and diagnosed one arteriovenous fistula (AVF) in each of 8 kidneys. Three of them were associated with pseudoaneurysms. Three of the patients with AVF who presented with macrohematuria underwent angiography. Therapeutic percutaneous embolization was performed in 2 of them. The remaining 6 patients were followed up with ICDUS. All the lesions had disappeared at the end of a 6-month period. We conclude that ICDUS is an easy and noninvasive imaging technique in the diagnosis of postbiopsy native renal AVFs. PMID- 7797663 TI - Placental infarction simulating a succenturiate lobe. PMID- 7797665 TI - Hepatic hydatid cyst communicating with the biliary tract. PMID- 7797664 TI - Ultrasound appearance of parotid Castleman's disease. PMID- 7797662 TI - Sonography of the costal cartilage: normal anatomy and preliminary clinical application. AB - Costal cartilages of 10 controls and 12 patients with Tietze's syndrome (n = 6), deformed (exaggerated bowing) cartilage (n = 4), focal enlargement (n = 1), and cancer-invaded cartilage (n = 1) were examined with ultrasonography. In controls, ultrasonography detected 237 of 240 costal cartilages (98.8%) and 58 of 105 intercartilage connections (55%) with three variations. Correlation with CT was available in 7 patients (1 Tietze's syndrome, 4 deformities, 1 cartilage enlargement, and 1 cancer) among 8 patients whose CT results were known to the sonographer. Sonography showed normal (n = 4) or marginally blurred (n = 2) cartilages in 6 Tietze's syndromes. Ultrasonography is a promising technique in the examination of costal cartilages. PMID- 7797666 TI - Ultrasound-guided transperineal needle biopsy of the prostate after abdominoperineal resection. PMID- 7797667 TI - Candida fungus balls presenting as intraventricular masses in cranial sonography. PMID- 7797668 TI - An easily made, low-cost, tissue-like ultrasound phantom material. PMID- 7797669 TI - A global perspective. PMID- 7797670 TI - You're invited. PMID- 7797672 TI - Permanent continuing education of nurses in Hungary. PMID- 7797671 TI - Continuing education in nursing in Japan. PMID- 7797673 TI - Continuing professional education: individual responsibility, collective consciousness. AB - Continuing professional education in the United Kingdom is discussed and the influences examined. Within a framework of national, nursing, and local perspectives, the issues and implications for the various individual agencies and personnel are identified. An overview is provided to include agendas for action. PMID- 7797674 TI - Continuing education in nursing: the Icelandic experience. PMID- 7797675 TI - Continuing education for nursing staff development through technical cooperation of Southeast Asian countries. PMID- 7797676 TI - Continuing education in nursing in Jamaica, West Indies. PMID- 7797677 TI - Continuing education in Brazil. AB - In the present study, we discuss some specific aspects of the National Health System of Brazil in terms of nursing practice, education, and investigation, which require further professional training through continuing education. With this objective, we shall report a historic view of how this process occurred and is being transformed in this country in an attempt to meet the social realities of our time. PMID- 7797678 TI - Continuing education in nursing in Kuwait. PMID- 7797679 TI - Faculty development: a transcultural experience. AB - A collaborative education program between Schools of Nursing at the Jordan University of Science and Technology and the University of Windsor, funded by the Canadian International Development Agency (CIDA), provides advanced clinical and theoretical education for Jordanian faculty and thus enriches the education of nursing students. This article describes the preparation of the faculty development proposal and the implementation of the project in a transcultural context, and identifies strengths and limitations of the project. Recommendations for effective strategies regarding international development in nursing education are made and a discussion of the benefits that ensued to both faculties is included. PMID- 7797680 TI - Inservice education in Turkey. PMID- 7797681 TI - Continuing education in Greece. PMID- 7797683 TI - Critical thinking. PMID- 7797682 TI - Continuing education in Saudi Arabia: the missed sonata. PMID- 7797684 TI - Walking around the elephant: a critical-thinking strategy for decision making. AB - The parable of the blind men and the elephant provides a metaphor for emphasizing important characteristics of critical thinking and strategies for decision making. The article describes critical thinking as a process and cognitive skill that functions in identifying and defining problems and opportunities for improvement; generating, examining and evaluating options; reaching conclusions and decisions, and creating and using criteria to evaluate decisions. Critical thinking improves the quality of professional and personal decisions. Critical thinking also contributes to the effectiveness of group decision making by creating synergy and collaboration. The article presents evidence of the crucial nature of critical thinking in nursing practice, management, and executive roles, and in the practice of continuing education and staff development. The article identifies and develops the major defining characteristics of critical thinking. Illustrating the characteristics in practical examples, the article suggests ways to foster critical thinking for ourselves, with our learners, with managers, and with our colleagues. PMID- 7797685 TI - The generic research protocol: an innovative technique to facilitate research skills development and protocol preparation. AB - Hospitals are increasingly delegating responsibility for initiating nursing research to nursing staff whose knowledge of and experience in conducting research may be limited. As a result, nurses involved in continuing education and staff development are increasingly involved in helping staff develop their research skills and prepare research protocols. The generic research protocol (GRP) is a computerized learning package that assists nursing staff in preparing a scholarly research protocol through step-by-step instruction and guidance. When used in two unrelated nursing studies, research skills of participating nursing staff were developed and protocol preparation facilitated. The time and editorial effort required for protocol preparation were reduced, and novice researchers were familiarized with research terminology and issues related to study design. PMID- 7797686 TI - The challenge: developing a preceptorship program in the midst of organizational change. AB - The implementation of educational programs during ongoing organizational change is a challenge. Our hospital nursing education department was successful in developing a department-wide preceptorship program during significant institutional change. This article outlines an analysis of the process of implementing such a program from the perspective of the unfreezing, moving, and refreezing components of change theory. An examination of the driving and restraining forces before and after the initiation of the program provides rationale for the success of the program. Factors that contributed to achievement of our goals include effective communication, senior administrative support, and education. From this analysis one could conclude that it is possible to initiate major educational initiatives during concurrent organizational change. PMID- 7797688 TI - Continuing education in South Africa. AB - An overview of continuing education in South Africa reveals that despite strong philosophical support a number of factors impede the developmental of an effective system of such education. Existing inadequacies have been exacerbated by the introduction in 1986 of a comprehensive program for entry into the profession, resulting in an overwhelming demand for continuing education for nurses who trained prior to that. Rural nurses in particular are disadvantaged, with nondegree continuing education being largely inaccessible. However, efforts to meet these needs are afoot, and two recent initiatives are described. PMID- 7797687 TI - Adapting to change: reconsidering staff development organization, design, and purpose. AB - Staff development educators must perform a balancing act between maintaining the routine learning services and responding to and facilitating the emergent learning needs that shape success. This article proposes a dual-track structuring to address both needs and to create a cutting-edge approach to organizational learning needs. PMID- 7797689 TI - A synopsis of continuing nursing education in Kenya. PMID- 7797690 TI - Community-based nursing education in Pakistan. AB - The nursing profession is not looked on favorably by Muslim families. In one rural area there were only three nurses for 1 million people. Community health and public health care have been lacking in the nursing curriculum. Therefore, preparing recruits for the community health nursing (CHN) posts in the Community Health Sciences Department (CHSD) and for faculty of the School of Nursing has involved a sequence of continuing education: inservice and on-the-job training in the CHSD and courses in the new BScN program. Those who joined with a diploma in nursing and a year of midwifery, and who followed this sequence, could be selected as Aga Khan University (AKU) scholars, and be sponsored for support in the two-year BScN program with its community health orientation. After two more years of advanced experience, the CHN is given the opportunity to apply for master's studies abroad. All who were accepted have returned to work at the Aga Khan University and have increased their career opportunities. PMID- 7797691 TI - Continuing education nursing program in Thailand. PMID- 7797692 TI - Nursing staff development and continuing education in Korea. PMID- 7797693 TI - Assessing beginning level competencies: the first step in continuing education. PMID- 7797694 TI - A reinforcement technique: the goody bag. PMID- 7797695 TI - Listening to children: medical treatment and consent. PMID- 7797696 TI - Search for meaning in long-term cancer survivors. AB - The purpose of this study was to explore search for meaning in long-term survivors of malignant melanoma and the relationship of this meaning to self blame and well-being. The sample consisted of 31 long-term melanoma survivors who had been free of disease for 5 years or longer. Measures included the Search for Meaning scale, a single item on self-blame and the Index of Well-Being. Data were analysed by descriptive statistics and t-tests. Findings revealed that 52% (n = 16) of the sample did search for meaning which resulted in an identifiable cause for their cancer and a quiet reassessment of life. Subjects indicating self responsibility for their cancer expressed a greater meaning search than the group who did not blame self (P < 0.01). Well-being scores were not significantly related to this search for meaning. Results suggest that for some survivors the cancer experience elicits a search for meaning which is significantly associated with self-blame. This study extends developing nursing theory on survivorship by providing insight into the meaning of the cancer experience in long-term survivors. PMID- 7797697 TI - Changing nurses' pain assessment practice: a collaborative research utilization approach. AB - It is not uncommon for a decade to pass between the time a research problem is identified and the time that research-based solutions are translated into standards for care. This quasi-experimental study demonstrated the effectiveness of a collaborative research utilization model directed towards the transfer of specific research-based knowledge (pain assessment) into practice for the purpose of helping to solve pain management problems. At the same time, nurses who participated in the model significantly improved their competency in research utilization and their attitudes towards research when compared to a control group who did not participate in the model. PMID- 7797698 TI - Health and memory in people over 50: a survey of a single-GP practice in England. AB - One hundred and forty people over the age of 50 randomly sampled from a single handed British general practice were screened for dementia using the Kendrick Cognitive Tests for the Elderly. The tests results were compared with actuarial data concerning health and health services provision. The results indicate that there are clear interrelations between low but non-dementing scores in memory and speed performance with the use of services, mobility levels and chronic disorders. PMID- 7797699 TI - Gender differences in care delivery and supervisory relationship: the case of psychogeriatric nursing. AB - In this paper the impact of gender differences within nursing is examined. Previous work has highlighted the disproportionate number of men in senior managerial positions in nursing and the perceived benefits which more males entering the profession may bring, for example increased status and higher pay. The present work addresses two domains where the impact of gender differences may importantly affect both policy and practice; first in the realm of care delivery and second in the area of supervisory relationships. The care received by male and female patients is studied, with particular attention being given to mixed wards. Differences between the care delivery of male and female ward staff are also discussed. Finally, differences in the supervisory roles of male and female charge nurses are examined. The research concludes that the inter-relationships between male and female ward staff and the way in which these impact upon the care received by patients is, as yet, little understood. However, as increasing numbers of males enter traditional female preserves within nursing, the need for a debate regarding the impact of gender differences is now essential. PMID- 7797700 TI - Older women's attitudes to cervical screening and cervical cancer: a New Zealand experience. AB - An in-depth series of interviews was undertaken amongst a small group of older, caucasian women, in Auckland, New Zealand. The study was part of the region's cervical screening programme. The aim of the study was to determine how the older woman's perceptions of cervical cancer and cervical screening services might be affecting her health-seeking behaviour. Healthy, caucasian women between 45 and 70 years of age were invited to participate. These women had either declined or delayed having regular cervical smears. Interviews were recorded and transcribed, then subjected to thematic analysis. Although small, the study is important in that it highlights cognitive, emotional, socio-economic and ego integrity barriers to regular cervical screening. Nurse clinicians have a major role in disease prevention and education for healthy older women. The findings provide a useful background for developing strategies to increase the uptake of cervical smears amongst older Caucasian women. They may also be viewed as a pilot for the development of questionnaires, or for further investigation of perceptions of older women in other ethnic groups. PMID- 7797701 TI - Pain: the views of elderly people living in long-term residential care settings. AB - While an individual's beliefs and attitudes have long been considered important factors in how people respond to pain, few studies have attempted to provide in depth descriptions of the nature of such pain beliefs and attitudes. The aim of this research was to investigate the views of pain and pain management practices held by elderly people living in long-term residential care settings. Ten 60-90 minute focus group interviews, each involving around five elderly people, were conducted in four large, long-term residential care settings in Brisbane, Australia. Categories of beliefs and attitudes regarding pain were identified following analysis of the verbatim transcripts of these interviews. Findings suggest that many elderly people living in long-term residential care settings may have become resigned to pain, that they are ambivalent about the benefit of any action for their pain and that they may be reluctant to express their pain. Implications of these beliefs and attitudes are discussed. PMID- 7797702 TI - Low-intensity, range-of-motion exercise: invaluable nursing care for elderly patients. AB - This study looked at the effect of a single session of mild exercise in a group of cognitively unimpaired institutionalized elderly patients, aged 70+, on tests of cognitive performance. Results indicate that mild exercise, such as range-of motion, does improve the ability to recall and that the effect lasts for at least half an hour. Mild exercise programmes appear to be a practical, low-cost nursing intervention that can enhance memory and independence. Programmes that are designed to meet individual needs and that are incorporated into daily routine and activities without imposing extra effort or inconvenience are more appealing to elderly patients. Exercise can be easily learned and implemented by nurses, personal care attendants or nurse aides. This is an extremely important consideration in a health care system that demands low-cost quality care. PMID- 7797703 TI - The process of social support: adjusting to life in a nursing home. AB - This study was designed to explore the process of social support during the course of adjusting to life in a nursing home. Qualitative data were gathered, through four sequential interviews of residents newly admitted to a nursing home, and from 12 months of participant observation in the setting. Residents' perceptions of supportive and non-supportive behaviours and their sources were identified and described. The findings indicated negligible change in perceptions of type or source of support over time. Emotional support and practical assistance emerged as the primary supportive and non-supportive behaviours from others, mainly nursing staff. Advice/guidance support was not mentioned. Residents who had lived in the nursing home for more than 1 year differed from new residents in the ability to extend support to others. Support interventions are suggested. PMID- 7797704 TI - Feminist teaching and the older nurse: the journey from resistance through anger to hope. AB - Some of the material presented in the journals of mature student registered nurses in two nursing research methodology courses are analysed. The classes were taught from a critical feminist perspective; that is, gender, race, sexual orientation and class issues were addressed as the science of ideas was explored. The students kept journals of their experiences throughout the process. While this was not a 'research' project in the usual sense of the word, material evolved which was primarily an evaluation of my teaching approach and their responses to it. Excerpts of this material were kept as they provide rich data providing insights into teaching strategies. Students cannot be identified in this analysis. It was found that, initially, most resisted the ideas of feminist theory, research and praxis. As the classes progressed, many feelings were of anger about the oppression they had experienced in the past at work and personally but had not understood. Finally, towards the end of term, many students expressed hope that they would be able to bring about some social change within the profession as a result of the ideas discussed in classes. However, several students remained unconvinced that feminism was the way to evoke change. PMID- 7797705 TI - Women's experiences of rheumatoid arthritis. AB - This paper is based on findings drawn from research undertaken within a qualitative framework of analysis. The purpose of the research was to explore women's experiences of rheumatoid arthritis. Three areas of concern to the women are identified and discussed in the light of relevant literature. They are as follows: seeking help, searching for meaning and uncertainty about symptoms. A major theoretical concern of both authors is to demonstrate the importance of placing patients' personal accounts of their experiences and understandings at the centre of nursing interest and practice. It is argued that there is a need to develop research studies of how patients experience disease, in order to develop a basis for good practice. PMID- 7797706 TI - Unequal access to midwifery care: a continuing problem? AB - For women of an ethnic minority the maternity services have been described as inappropriate, inaccessible and inadequate. It is hoped that the contents of this paper will raise awareness amongst health professionals of the continuing problems faced by women trying to overcome a language barrier. PMID- 7797707 TI - The process of analysis during a grounded theory study of men during their partners' pregnancies. AB - This research builds on the work of Barclay (1993) who studied couples during pregnancy and discovered that there was a mismatch between sexual interest levels of men and women during pregnancy. As well, little is known about the social and emotional experiences of men during their partners' pregnancies. One antenatal group consisting of six men, whose partners were in the second trimester of pregnancy, attended a series of five meetings and subsequent individual interviews. Additional data and insights were gained by the researcher and the research assistant attending other antenatal classes with men and women present. The research data consisted of transcripts of tape-recorded interviews, group discussions, observations and field notes made by the researcher and co-leader following each of the group sessions. The aim was systematically to develop a substantive grounded theory which was drawn from the experiences of the men during this transitional period in their lives. This paper discusses the process of analysis which led to the central phenomenon, the core category of the research, around which the grounded theory is built. Five theoretical constructs emerged from the data collected: (a) ambivalence in the early stages of pregnancy, (b) relationship with baby not real, (c) how should I be as a father?, (d) coping with the changing roles and lifestyle, and (e) disequilibrium in relationship with female partner. The last construct emerged as the basic social process. The nature of this relationship changed over the duration of the pregnancy. Emotional turmoil and anxiety in men contributed to the 'mismatch' in male and female expectations of the relationship.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797709 TI - The application of the ideas of Frantz Fanon to the practice of mental health nursing. AB - This paper is based on an extensive review of the published literature which refers to the clinical and social psychology of Frantz Fanon, and seeks to establish the relevance of Fanon's psychological thought to the practice of mental health nursing in the 1990s. The writer sets out the key principles of Fanon's clinical and social psychology, and engages with the theoretical problems which arise from the close relationship between Fanon's psychological theories and his involvement with violent revolutionary politics. After discussing the links between Fanon's unique psychology and the work of the anti-psychiatrists of the 1960s and later critiques of mental health care, the writer argues that the development and adoption of a neo-Fanonist approach to the practice of mental health nursing would address many of the problems of current mental health care practice. In particular, the principles of Fanon's psychology address many of the concerns about disempowerment of service users which have been highlighted in work by feminist and anti-racist writers, and by members of the Mental Health Service Users' Movement. PMID- 7797710 TI - Meaning attached to compliance with self-care, and conditions for compliance among young diabetics. AB - This paper presents a hypothetical model of the compliance with self-care of young diabetics, its features, its meaning to them and the preconditions for compliance with self-care. The aim of this research was to develop a model to clarify and expand existing knowledge concerning compliance with self-care among young diabetics and to produce new ideas for planning and implementing this care. Four categories of behavioural pattern were identified. Those young people with good compliance experienced a sense of well-being, health, and freedom. They were responsible, active, and well motivated in voluntarily implementing self-care. The second group were those whose actions deviated only slightly from health regimens but who had undergone many negative experiences with self-care. Their actions were guided only by compulsion. The third group were consciously non compliant. Their constant neglect of health regimens was associated with feelings of poor health, fears and indifference. They were not motivated to comply, felt that the aims set were too high and the self-care programme too tightly regimented. They felt that they received no encouragement. The young people belonging to the fourth group frankly refused to pursue self-care. Their non compliance was seen by them as an issue of freedom. In effect, their friends controlled their lives, and they felt that their self-care was all the more unnecessary since nobody encouraged them to keep to it. PMID- 7797711 TI - Evaluating clinical educators: an employer's perspective. AB - An Australian school of nursing's attempt to introduce an evaluation process required by management for clinical educators involved in undergraduate preregistration education is discussed. Reliance on student feedback and clinical agencies' perceptions of the quality of teaching were seen as inadequate mechanisms for evaluation. The evaluation process adopted incorporated observation of the educators together with self-reflection on their performance. We conclude that post-briefings were poorly used and generally not reflective. Educators relied heavily on their clinical skills and used a limited range of teaching strategies. Whilst evaluation of clinical educators was time consuming and therefore costly, it is argued that it is essential to the integrity of the course. The evaluation process has provided direction for support and development of clinical educators within the context of the curriculum. PMID- 7797708 TI - Parental participation in care: a critical review of the literature. AB - The literature reviewed demonstrates that parental participation is a complex issue which has been viewed mainly in a fragmented manner which does not recognize the integrated holistic nature of parent-nurse partnership. There is a dearth of research which focuses upon parents' perspectives and expectations of participation. Furthermore, there is an assumption that parental participation is unproblematic which precludes the identification of social and environmental constraints. The current level of knowledge about nurses' attitudes regarding parental participation is limited. There is an absence of clear indicators of how parental participation may be facilitated and supported in the institutional setting. It is proposed that further research is required which determines the extent of parental participation and which considers the lived experiences of both the parents and nurses of parental participation. Improved care for children and families could result from efforts directed to those endeavours. PMID- 7797713 TI - Collegiality, adaptation and nursing faculty. AB - Many nurse educators in the United Kingdom are currently faced with the challenge of change, of leaving the culture of the British National Health Service and integrating into the culture of tertiary education. This paper reports on a study of the process of developing collegial relationships in the context of a new collaboration to develop a combined curriculum for nurses within a tertiary institution. The aims of the study were to analyse this process of integration and to identify the conditions that enhanced the development of collegiality between members of the nursing group. The case study centred on the analysis of data collected on video during unstructured interviews with the five members of the group. Data were analysed using Burnard's method of thematic content analysis. The paper argues that during the transition from the National Health Service to tertiary education, individual nurse educators and their managers must address problems related to issues such as 'ingroupism', nursing the students, perceived difference between nurse academics and other academics, and expectations of power-relationships. PMID- 7797712 TI - Nursing faculty practice: challenges for the future. AB - Just as artists need to create their own art, so nursing instructors need to practise nursing. However, traditional educational settings and clinical placements limit the capacity of nursing instructors to practice nursing directly with clients. The creation of a nursing faculty practice model in Canada, whereby teaching roles and responsibilities are combined with clinical practice, is discussed within the context of a community college environment. A nurse-managed health centre is suggested as an innovative practice arena which is more in line with the changes in the health care system. PMID- 7797714 TI - Staff perceptions of organization change of treatment delivery on an addiction unit. AB - The Work Environment Scale was used to assess staff perceptions of a change in a treatment programme for problem drinkers. A more cost-effective 2-week research based day-patient programme, which included the concept of matching, replaced a 5 week cognitive behavioural in-patient programme. The maintenance of a positive work environment was attributed to the meeting of staff expectations, a cognitive behavioural ideology, and the establishment of a research culture. The study highlights the importance of the thorough preparation of staff for change, and their active involvement in the process in settings where work satisfaction is already above the average level for mental health facilities. PMID- 7797715 TI - Continuing professional education: luxury or necessity? AB - The author sets out to define what is meant by continuing professional education, the implications of the terminology and the contribution that it makes to nursing. She then moves on to discuss the distinction between education and learning, and the importance of 'life-long learning' to nursing. The relative merits of voluntary and compulsory education are considered and the attitudes and expectations of both nurses and their managers are examined. Obstacles to the up take of educational opportunities are outlined, and some of the issues behind this are explored. The assessment of educational requirements and the evaluation of educational offerings are reviewed, along with the importance of assuring quality, not only in the context of proposals for postregistration education and the current market ethos in the United Kingdom, but also with regard to the potential benefits to be gained in the health care of the general public. PMID- 7797716 TI - Planning nursing education for the 21st century. AB - In looking towards the 21st century, the faculty at the Presbyterian Hospital School of Nursing, along with the Presbyterian Health Services Corporation and Queen's College, adopted a 1-2-1 programme. The process of developing a new nursing curriculum is presented as the task force proceeded from the philosophy and goals to conceptual framework and curriculum objectives. After discussions with nurse administrators and educators, extensive literature reviews and brainstorming sessions, concepts and subconcepts were chosen to form a philosophy. The metaparadigm of nursing and other related concepts were then organized into a conceptual framework. Ongoing communication and feedback from the faculty ensured group ownership of all documents. The eclectic organizational scheme was a good fit for a large faculty with differing beliefs and values about a nursing curriculum. The process of developing a future orientated nursing curriculum has been exciting, challenging and rewarding. The faculty is committed to the new philosophy, goals and conceptual framework and believe that the 1-2-1 programme will educate future practitioners who are prepared to meet the challenges and changes in health care for the 21st century. PMID- 7797717 TI - Talking realistically about nursing: a thematic analysis of nursing course selection interview discourse. AB - This study examines the dialogue within selection interviews for places on a graduate nursing programme. The analysis focuses upon the way in which a 'realistic' knowledge of nursing is tested for, and demonstrated through, particular discursive themes. These themes reflect a wider social acceptance of accountable rational decision-making. It is argued that applicants who are able to draw upon the interpretative resources necessary to justify their nursing course application in these terms are more likely to be evaluated positively. PMID- 7797718 TI - Hindsight bias in reflective practice: an empirical investigation. AB - Reflection is seen as a central component in the education and practice of nurses. It is through critical reflection on one's practice that expertise can be assured. This faith in the process of reflection has influenced much of pre and post registration nurse education. It is only in the past few years that reflection as a technique has being criticized. A small-scale study investigating the phenomenon of hindsight bias and its consequence on the reflective process is described. The effects of the hindsight bias is to influence people's recollection of events once they know the final outcome. The present study does indicate that nurses are susceptible to such a bias, which would question the validity of reflection as a way to enhance patient care. There is an urgent need to clarify the reflective process and then to examine its effect on patient outcomes. PMID- 7797719 TI - Managerial strategy and nursing commitment in Australian hospitals. AB - This study examined the relationship of managerial strategy and nursing commitment in Australian hospitals. The general principles of managerial strategy and employee response were illustrated and the meaning of commitment and resistance were defined. Data were collected by questionnaire survey and interviews. The result demonstrated that the middle manager/nurse unit manager played an important role in generating nursing commitment in the workplace. Trust and identification were the most relevant components of nursing commitment. However, the study also found that there was still a high degree of distrust between senior management and nurses. Change strategies which nurse managers could apply to promote greater organizational commitment in nursing are discussed. PMID- 7797720 TI - Correlates of nursing diagnosis quality in public health nursing. AB - The purpose of this study was to identify the relationship between the number and quality of nursing diagnoses generated by public health nurses (PHNs), and the use of different assessment databases (nursing or medical). In addition, the effect of experience with theory-based nursing practice on the number and quality of the diagnoses was examined. A convenience sample of 37 PHNs employed in two county health units provided the subjects for this study. One agency had implemented theory-based nursing practice; the other had not. Analysis of the results revealed that use of a nursing database significantly affected the number of diagnoses generated by PHNs. However, the database type did not significantly affect the quality of the diagnoses. PHNs' experience with theory-based practice had no significant effect on the number or quality of nursing diagnoses generated by PHNs, irrespective of database. PMID- 7797721 TI - Dancing with regulators. PMID- 7797722 TI - Managed care and dentistry. PMID- 7797723 TI - California clarification. PMID- 7797724 TI - Dental implants. PMID- 7797725 TI - Bleaching patients pleased with long-term results. PMID- 7797726 TI - Smoking inhibits healing after periodontal treatment. PMID- 7797727 TI - The sweet smell of serenity. PMID- 7797728 TI - Super-strong ceramic restorative developed. PMID- 7797729 TI - Treatment regimens in preventive and restorative dentistry. AB - Due in part to a lack of appropriate training and the incentive of adequate compensation, preventive dentistry in the United States has focused on prophylaxis and fluoride application. Dentistry must shift its attention to developing standardized protocols for "preservative dentistry"--diagnosing caries, assessing and monitoring caries risk, arresting active caries and remineralizing non-cavitated lesions. This article addresses shortcomings in preventive dentistry and proposes a plan for treatment standardization that can ensure optimum treatment and, ideally, lead to adequate compensation. PMID- 7797730 TI - Percutaneous injuries in dentistry: an observational study. AB - The authors conducted an observational study of the frequency and circumstances of percutaneous injuries among dental residents. Their findings suggest that most percutaneous injuries sustained by these dental residents occurred extraorally and were associated with denture impression procedures. Some injuries may be preventable with changes in techniques or instrument design. PMID- 7797731 TI - Comparing the resistance of dentin bonding agents and pins in amalgam restorations. AB - This in vitro study involving 84 caries-free molar specimens examined the resistance of complex amalgam restorations retained by two dentin bonding agents- Amalgambond and Amalgambond Plus--four regular TMS pins, six regular TMS pins and four pins in conjunction with Amalgambond. Analysis indicated that the Amalgambond restorations were significantly weaker than the other types. Amalgambond Plus restorations were significantly stronger than the Amalgambond restorations but not different from the remaining groups. The authors concluded that complex amalgam restorations should be retained with a combination of adhesive and mechanical retention. PMID- 7797733 TI - How dentists perceive the effects of orthodontic extraction on facial appearance. AB - In recent years, orthodontic treatment, particularly that involving premolar extractions, has been alleged to cause flat facial profiles. Those who make such assertions also claim to be able to instantly identify from a distance faces of patients who have received orthodontic treatment. These are strong claims that could profoundly affect the public's perception of dentistry and its specialties. This study examined whether dentists could distinguish between profiles of treated and untreated patients as well as between patients who had undergone extraction and those who had not. PMID- 7797732 TI - Using air-abrasive technology to diagnose and restore pit and fissure caries. AB - National Institute of Dental Research surveys indicate that the incidence of pit and fissure caries constitutes a higher proportion of the total caries incidence among U.S. teens and children than in the past. Air-abrasive technology may provide a more conservative alternative in the diagnosis and treatment of pit and fissure caries than traditional techniques using handpieces. The authors review characteristics of pit and fissure lesions and discuss methods for diagnosing and treating these lesions using air-abrasive technology. PMID- 7797734 TI - General dentists' patterns of restoring endodontically treated teeth. AB - The manner in which endodontically treated teeth are restored influences tooth longevity and the cost of treatment. This article describes a study of how surveyed general dentists restored endodontically treated teeth and whether their methods were consistent with those suggested in the literature. Some patterns of restoration did reflect the literature's recommendations, but overall the findings call into question some of the ways in which post-endodontic restorative care is carried out. PMID- 7797735 TI - A promising new category of dental cements. PMID- 7797736 TI - The oral health of U.S. Hispanics: evaluating their needs and their use of dental services. AB - Data from the 1985-1986 National Survey of Oral Health in U.S. Adults and Seniors showed that the oral health of Hispanic American adults and seniors was comparable to that of black adults and seniors. White adults and seniors had better oral health than their minority counterparts for all measures observed and were better able to afford dental care. PMID- 7797737 TI - Percutaneous revascularization of chronic coronary occlusions: an overview. AB - Patients with a chronic coronary occlusion often undergo coronary angiography after weeks to months of occlusion. The published reports underestimate the extent of this problem because such patients are often arbitrarily assigned to receive medical therapy or undergo bypass surgery as a result of poor success with percutaneous revascularization and substantial restenosis. Thus, there is controversy about the role of angioplasty in this patient cohort. The goal of this overview was to evaluate the available information about angioplasty in chronic coronary occlusions. The primary indication for attempted recanalization of a chronic coronary occlusion has been symptomatic angina pectoris. Anginal status often improves after successful procedures (70% vs. 31% with a failed procedure); left ventricular function may improve; and subsequent referral for coronary artery bypass graft surgery is uncommon (3% vs. 28% in unsuccessful cases). Successful recanalization is achieved in approximately 65% of attempted procedures. Inability to cross the stenosis with a guide wire is the most common cause of procedural failure. Statistically significant predictors of procedural success include older occlusions (75% < 3 months old vs. 37% > or = 3 months old), absence of any anterograde flow through the occlusion (76% with vs. 58% without), angiographically abrupt-appearing occlusions (50% vs. 77% with tapered occlusions), presence of bridging collateral vessels (23% with vs. 71% without) and lesions > 15 mm. Procedural complications occur at a slightly lower incidence than in angioplasty of high grade subtotal stenoses. Long-term success is limited, and restenosis can be expected in > 50% of the patients. The experience with chronic total occlusions of saphenous vein bypass grafts is small, but there appear to be limited procedural success and significant procedural complications, particularly associated with distal emboli. The role of new pharmacologic agents has yet to be defined and that of new devices has been disappointing so far, but further technologic advances are on the horizon. PMID- 7797738 TI - Effect of prolonged catecholamine infusion on immunoregulatory function: implications in congestive heart failure. AB - OBJECTIVES: This study sought to characterize the effects of prolonged catecholamine infusion on immunoregulatory cell traffic and activation. BACKGROUND: Immunoregulation has been shown to be partially controlled by the sympathetic nervous system. Although short-term elevation of catecholamine levels is known to alter immunoregulatory cell traffic and activation, the effects of prolonged heightened sympathetic nervous system activity have not adequately been studied. We believe that the alterations in immune function seen in patients with congestive heart failure are linked to a prolonged elevation of circulating catecholamine levels. METHODS: To characterize the effects of prolonged elevation of catecholamine levels, rats received 4 weeks of constant infusion of epinephrine or norepinephrine through implanted osmotic minipumps. Peripheral and splenic leukocyte subsets, T cell proliferation and interleukin-2 receptor expression were quantified. Antibody production to the novel antigen keyhole limpet hemocyanin was assessed over the 4-week treatment period. RESULTS: Both epinephrine and norepinephrine caused significant splenic atrophy and cardiac hypertrophy; both were blocked by propranolol. Epinephrine induced lymphocytosis; both catecholamines caused an increase in natural killer cells. In the spleen, both epinephrine and norepinephrine led to a dose-dependent decrease in total T cells, suppressor/cytotoxic T cells and natural killer cells and a significant increase in B cells. Epinephrine at the low dose enhanced mitogen-induced proliferation and interleukin-2 receptor expression. Norepinephrine at the low dose appeared to diminish proliferation. Epinephrine tended to inhibit IgG antibody production, whereas norepinephrine had no effect. CONCLUSIONS: The results of our study indicate that prolonged elevation of catecholamine levels alters immune cell proliferation and differentiation. These alterations differ greatly from those induced by short-term stimulation but, for the most part, parallel those found in patients with congestive heart failure. We postulate that the shifts in immunoregulatory cell type and function seen in patients with congestive heart failure are due, in part, to longstanding increases in circulating catecholamine levels and may play an important role in the pathogenesis and progression of disease. PMID- 7797739 TI - Myocardial contrast echo effect: the dilemma of coronary blood flow and volume. AB - Despite the useful information provided by myocardial contrast echocardiography, the meaning of myocardial contrast intensity remains elusive. This review is meant to define the contribution of physical and biologic factors in producing myocardial contrast and to elucidate the relative roles of coronary blood flow and intramyocardial blood volume in determining contrast effect. The main physical factors influencing the contrast echo effect include the properties of microbubbles as scattering elements (mainly their radius, compressibility, stability and concentration), electronic signal processing, instrument setting and contrast-induced signal attenuation. The effect of these factors can be limited by an appropriate experimental or clinical setup. Biologic factors are less easily controllable, and changes in coronary blood flow and alterations in myocardial blood volume appear to be the main determinants of myocardial contrast intensity. Moreover, these factors influence contrast intensity in opposite directions. Both the area under the time-intensity curve and the mean transit time of myocardial contrast are inversely related to coronary blood flow but directly related to myocardial vascularity and blood volume. Therefore, an increase in coronary flow not accompanied by an increase in myocardial vascularity and volume is accompanied by a decrease in the area under the curve and mean transit time of contrast. Conversely, an increase in coronary flow mediated by augmented myocardial vascularity and volume will produce an increase in the area under the curve and mean transit time. A better understanding of the physical and biologic determinants of contrast echo intensity will be fundamental in the clinical application of new agents and technologies. PMID- 7797740 TI - Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. AB - OBJECTIVES: This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. BACKGROUND: Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. METHODS: Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. RESULTS: Sixty-six patients underwent coronary angioplasty. Angiographic success (< or = 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 +/- 14 (mean +/- SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 +/- 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 +/- 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 +/- 7 months after operation. CONCLUSIONS: Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization. PMID- 7797742 TI - Angioscopic findings during coronary angioplasty of coronary occlusions. AB - OBJECTIVES: This study sought to elucidate angioscopic findings in totally occluded vessels before and after intervention. BACKGROUND: Coronary angioscopy allows direct visualization of the lumen surface of the coronary arteries; however, the utility of coronary angioscopy during coronary angioplasty of vessels with a total occlusion is unknown. METHODS: Twenty-one consecutive patients (mean [+/- SD] 58 +/- 9 years, range 39 to 77; 3 women, 18 men) undergoing dilation of an occluded vessel were studied with coronary angioscopy. Occlusions were classified as functional in 8 patients (Thrombolysis in Myocardial Infarction [TIMI] flow grade 1) and anatomic in 13 (TIMI flow grade 0). Once the guide wire had crossed the occlusion, coronary angioscopy was attempted before and after angioplasty. RESULTS: In all patients, coronary angioscopy before dilation visualized protruding material occluding the coronary lumen where the guide wire was wedged. The occlusion consisted of red thrombus in 19 patients (90%) (2 with isolated occlusive thrombus, 17 with thrombus associated with atherosclerotic plaque) and protruding yellow plaque in 2 patients (10%). However, on angiography only 7 occlusions (33%) had data consistent with thrombus (p < 0.01 vs. coronary angioscopy). Successful dilation was obtained in 20 patients. After dilation, coronary angioscopy was repeated in 18 patients, revealing residual thrombus with plaque in 16 (89%) and a residual yellow plaque in 2. In addition, coronary angioscopy revealed coronary dissections in 13 patients (72%); however, angiography revealed dissections only in 10 patients (55%) and residual thrombus in 2 (10%) (p < 0.001). In one patient, coronary angioscopy visualized silent distal embolization of a red thrombus not previously recognized on angiography. CONCLUSIONS: Before intervention, coronary angioscopy provides unique insights into the pathologic substrate of occluded coronary vessels. An occlusive plaque with thrombus is the most common underlying substrate in these lesions. After successful dilation, angiographically silent mural thrombus is seen in most patients. This information could be used to assist in the selection of candidates and type of coronary interventions and could also prove to be of prognostic value in patients with occluded vessels. PMID- 7797741 TI - Dynamic cardiomyoplasty: effect of discontinuing latissimus dorsi muscle stimulation on left ventricular systolic and diastolic performance and exercise capacity. AB - OBJECTIVES: This study sought to assess the short-term effect of discontinuing latissimus dorsi muscle stimulation on left ventricular systolic and diastolic performance and exercise tolerance in patients with improved functional status by cardiomyoplasty, in whom latissimus dorsi muscle was fully conditioned. BACKGROUND: Cardiomyoplasty has consistently improved the functional status of patients, but the short-term effect of latissimus dorsi muscle contraction has not been assessed in these patients. METHODS: Right-heart catheterization, Doppler-echocardiography and maximal exercise testing with expired gas analysis were performed in 10 patients with congestive heart failure who had undergone cardiomyoplasty at least 6 months earlier. Data were obtained when the latissimus dorsi muscle was stimulated every other systole and after stimulation was discontinued for 1 h. The power of this study to detect a 10% difference was > 80%. RESULTS: After cardiomyoplasty, left ventricular ejection fraction increased from 0.22 +/- 0.08 (mean +/- SD) to 0.27 +/- 0.07 after 6 months (p < 0.02 vs. before cardiomyoplasty) and to 0.24 +/- 0.09 after 1 year; functional class went from 3.0 +/- 0.0 to 2.0 +/- 0.5 after 6 months and to 2.0 +/- 0.7 after 1 year (both p < 0.001 vs. before cardiomyoplasty). After discontinuation of latissimus dorsi muscle stimulation, cardiac index did not change (2.28 +/- 0.45 vs. 2.30 +/ 0.46 liters/min per m2). Mean systemic arterial and pulmonary capillary wedge pressures were also similar (85.2 +/- 6.0 vs. 88.4 +/- 5.6 mm Hg and 14.9 +/- 7.1 vs. 13.6 +/- 6.8 mm Hg, respectively). Doppler E/A ratio decreased from 1.04 +/- 0.33 to 0.83 +/- 0.25 (p < 0.02), suggesting that left ventricular diastolic function may have been improved by latissimus dorsi muscle stimulation. Peak oxygen consumption was unaltered (1,633 +/- 530 vs. 1,596 +/- 396 ml/min). CONCLUSIONS: Alterations in left ventricular diastolic rather than systolic function may be responsible for the long-term clinical benefits of cardiomyoplasty. PMID- 7797745 TI - Comparison of transesophageal and intracardiac electrophysiologic studies in characterization of supraventricular tachycardia in pediatric patients. AB - OBJECTIVES: This study sought to determine the accuracy of transesophageal electrophysiologic studies in diagnosing and characterizing various mechanisms of supraventricular tachycardia in pediatric patients. BACKGROUND: Transesophageal electrophysiologic studies are a relatively noninvasive means of characterizing supraventricular tachycardia. Although widely used, to our knowledge no data exist that directly compare information obtained from transesophageal electrophysiologic studies with that from intracardiac electrophysiologic studies. METHODS: We reviewed the records of 57 pediatric patients undergoing both transesophageal and intracardiac electrophysiologic studies at our institution. The results of these studies were compared with respect to mechanism of tachycardia, localization of accessory atrioventricular (AV) connections (if present) and characterization of anterograde accessory connection conduction properties. RESULTS: Tachycardia mechanisms were concordant in 56 of 57 patients: orthodromic reciprocating tachycardia in 43, antidromic reciprocating tachycardia in 1, both orthodromic and antidromic tachycardia in 2, AV node reentrant tachycardia in 5, atrial reentrant tachycardia in 4 and ectopic atrial tachycardia in 2. Of 29 patients with orthodromic reciprocating tachycardia using a concealed accessory connection, transesophageal study predicted the accessory connection site through changes induced by transient bundle branch block in 12. By the Bland-Altman method in 14 patients with pre-excitation, the anterograde accessory connection effective refractory period determined by transesophageal study compared favorably with that determined by intracardiac study (mean difference 5.0 ms, limits of agreement -55 and 65 ms). CONCLUSIONS: Transesophageal electrophysiologic studies are a highly accurate means of diagnosing and characterizing various mechanisms of supraventricular tachycardia in pediatric patients. PMID- 7797743 TI - Percutaneous transluminal coronary angioplasty as a first revascularization procedure in single-, double- and triple-vessel coronary artery disease. AB - OBJECTIVES: We sought to compare in-hospital and long-term outcome after angioplasty in patients with single-, double- and triple-vessel disease. BACKGROUND: Coronary angioplasty is increasingly used in patients with multivessel disease. METHODS: The source of data was the clinical data base at Emory University. Patients who had previous coronary revascularization or who underwent angioplasty in the setting of acute myocardial infarction were excluded. RESULTS: Of 10,783 patients, 71% had one-vessel, 24% two-vessel and 5% three-vessel disease. Age, male gender, diabetes, hypertension, history of previous myocardial infarction, Canadian Cardiovascular Society class III or IV angina and congestive failure all increased with severity of disease. Complete revascularization was achieved in most patients with one-vessel disease, in a minority with two-vessel disease and rarely in those with three-vessel disease. Emergency coronary bypass surgery increased from 1.7% with one-vessel disease to 3.2% with three-vessel disease. Q wave myocardial infarctions could not be shown to vary significantly with severity of disease. The mortality rate increased from 0.2% with one-vessel disease to 1.2% with three-vessel disease. The number of vessels diseased was a multivariate correlate of in-hospital and long-term mortality. The 1-, 5- and 10-year survival was 0.99, 0.93 and 0.86 for one-vessel disease and 0.97, 0.89 and 0.76 for two-vessel disease, respectively. The 1-, 5- and 9-year survival was 0.95, 0.85 and 0.70 in three-vessel disease, respectively. Freedom from myocardial infarction, coronary bypass surgery and repeat angioplasty was also lower with more severe disease. CONCLUSIONS: Patients have increasing in-hospital and long-term mortality as the severity of disease increases. There is also an increased incidence of myocardial infarction and revascularization procedures with more severe disease. PMID- 7797744 TI - Transesophageal echocardiography predicts mortality in critically ill patients with unexplained hypotension. AB - OBJECTIVES: This study sought to determine the prognostic yield and utility of transesophageal echocardiography in critically ill patients with unexplained hypotension. BACKGROUND: Transesophageal echocardiography is increasingly utilized in the intensive care setting and is particularly suited for the evaluation of hypotension; however, the prognostic yield of transesophageal echocardiography in these patients is unknown. METHODS: We prospectively studied 61 adult patients in the intensive care unit with sustained (> 60 min) unexplained hypotension. Both transthoracic and transesophageal echocardiography were performed, and results were immediately disclosed to the primary physician, who reported any resulting changes in management. Patients were classified on the basis of transesophageal echocardiographic findings into one of three prognostic groups: 1) nonventricular (valvular, pericardial) cardiac limitation to cardiac output; 2) ventricular failure; and 3) noncardiac systemic disease (hypovolemia or low systemic vascular resistance, or both). Primary end points were death or discharge from the intensive care unit. RESULTS: A transesophageal echocardiographic diagnosis of nonventricular limitation to cardiac output was associated with improved survival to discharge from the intensive care unit (81%) versus a diagnosis of ventricular disease (41%) or hypovolemia/low systemic vascular resistance (44%, p = 0.03). Twenty-nine (64%) of 45 transthoracic echocardiographic studies were inadequate compared with 2 (3%) of 61 transesophageal echocardiographic studies (p < 0.001). Transesophageal echocardiography contributed new clinically significant diagnoses (not seen with transthoracic echocardiography) in 17 patients (28%), leading to operation in 12 (20%). CONCLUSIONS: Transesophageal echocardiography makes a clinically important contribution to the diagnosis and management of unexplained hypotension and predicts prognosis in the critical care setting. PMID- 7797746 TI - Left ventricular dimensions and autonomic balance during head-up tilt differ between patients with isoproterenol-dependent and isoproterenol-independent neurally mediated syncope. AB - OBJECTIVES: This study sought to elucidate differences in mechanisms of neurally mediated syncope between patients with syncope induced by head-up tilt alone and those requiring isoproterenol infusion to induce syncope during head-up tilt. BACKGROUND: Some patients with neurally mediated syncope require isoproterenol to induce syncope during head-up tilt (isoproterenol dependent), and others do not (isoproterenol independent). Differences in mechanisms between these two groups have not been well elucidated. METHODS: A 60 degrees head-up tilt test was performed in 13 patients with isoproterenol-independent syncope (Group I, mean [+/- SD] age 28 +/- 12 years), 14 patients with isoproterenol-dependent syncope (Group II, mean age 34 +/- 14 years) and 20 control subjects without syncope (Group III, mean age 32 +/- 12 years). Left ventricular size and contractility were determined by echocardiography, and sympathovagal balance was determined with power spectral analysis of heart rate variability using a maximal entropy method. RESULTS: Group I patients had smaller left ventricular dimensions than Group II and III during baseline tilt. During head-up tilt with isoproterenol infusion (0.01 to 0.04 microgram/kg body weight per min), left ventricular dimensions decreased to the same extent in Groups II and III, but fractional shortening was greater in Group II than in Group III at the end of the tilt. The ratio of low (0.05 to 0.15 Hz) to high frequency (0.15 to 1.0 Hz) component became greater in Group I than in Groups II and III during the last period of baseline tilt. However, the ratio was greater in Group II than in Group III during the last period of the tilt with isoproterenol. CONCLUSIONS: Patients with isoproterenol-independent syncope had an exaggerated decrease in left ventricular size and sympathetic predominance preceding syncope during head-up tilt. In contrast, in patients with isoproterenol-dependent syncope, similar changes in autonomic nervous balance were evident only during isoproterenol infusion in addition to head-up tilt. PMID- 7797747 TI - Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction. AB - OBJECTIVES: The aim of this study was to estimate the value of QT dispersion measurement from the standard 12-lead electrocardiogram (ECG) in identifying patients susceptible to reentrant ventricular tachyarrhythmias after a previous myocardial infarction. BACKGROUND: Variability in QT interval duration on the different leads of the 12-lead ECG has been proposed as an indicator of risk for ventricular arrhythmias in different clinical settings, but the value of QT dispersion measurement in identifying patients at risk for reentrant ventricular tachyarrhythmias after myocardial infarction is not known. METHODS: The QT interval duration, QT dispersion and clinical and angiographic variables were compared between 30 healthy subjects; 40 patients with a previous myocardial infarction but no history of arrhythmic events or inducible ventricular tachycardia during programmed electrical stimulation; and 30 postinfarction patients with a history of cardiac arrest (n = 12) or sustained ventricular tachycardia (n = 18) and inducible, sustained monomorphic ventricular tachycardia by electrical stimulation. RESULTS: Dispersion of the corrected QT interval (QTc) differed significantly between the study groups and was significantly increased in patients with susceptibility to ventricular tachyarrhythmias ([mean +/- SD] 104 +/- 41 ms) compared with that in both healthy subjects (38 +/- 14 ms, p < 0.001) and postinfarction patients with no susceptibility to arrhythmias (65 +/- 31 ms, p < 0.001). Maximal QT interval duration was also prolonged in the group with arrhythmias compared with that in the other groups (p < 0.001). Multivariate analysis, including clinical and angiographic variables, QT dispersion and maximal QT interval, showed that QT dispersion was the independent factor that most effectively identified the patient groups with and without susceptibility to ventricular tachyarrhythmias (p < 0.001). CONCLUSIONS: Increased QT dispersion is related to susceptibility to reentrant ventricular tachyarrhythmias, independent of degree of left ventricular dysfunction or clinical characteristics of the patient, suggesting that the simple, noninvasive measurement of this interval from a standard 12-lead ECG makes a significant contribution to identifying patients at risk for life-threatening arrhythmias after a previous myocardial infarction. PMID- 7797748 TI - Stress echocardiography: comparison of exercise, dipyridamole and dobutamine in detecting and predicting the extent of coronary artery disease. AB - OBJECTIVES: This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and echocardiographic variables, the mechanisms by which exercise and dobutamine induce ischemia. BACKGROUND: The diagnostic value of stress echocardiography has been widely reported, but the specific effects of exercise, dipyridamole and dobutamine have not been directly compared. Furthermore, no echocardiography study has evaluated left ventricular volume changes at ischemic threshold during exercise and dobutamine administration. METHODS: One hundred patients with suspected (Group A, n = 60) or known (Group B, n = 40) coronary artery disease underwent all three tests in random order. RESULTS: In Group A, the sensitivities of exercise (mean 76%, 95% confidence interval [CI] 58% to 94%) and of dobutamine echocardiography (72%, 95% CI 53% to 91%) were higher than that of dipyridamole (52%, 95% CI 31% to 73%; p = 0.01 and p = 0.02, respectively). Specificity did not differ significantly among tests (94% for exercise [95% CI 86% to 100%] and 97% for dipyridamole and dobutamine [95% CI 91% to 100%]). Accuracy was identical for exercise and dobutamine (87%) and higher than that for dipyridamole (78%, p = 0.06). In Group B, the accuracy in predicting coronary disease extent was 71% for exercise, 33% for dipyridamole and 75% for dobutamine. At ischemic threshold, end-systolic volume index and the ratio of systolic blood pressure to end-systolic volume, a variable related to myocardial contractility, were significantly lower and higher, respectively, with dobutamine than during exercise (p < 0.05). CONCLUSIONS: In a clinical setting, exercise echocardiography should represent the first diagnostic approach because it has high diagnostic efficacy and provides additional information on exercise capacity; pharmacologic stress, particularly that of dobutamine, provides a pivotal diagnostic tool when exercise is not feasible or its results are nondiagnostic. Our preliminary data on echocardiographic evaluation at ischemic threshold support the view that myocardial contractility is a major factor in inducing ischemia during dobutamine infusion. PMID- 7797749 TI - Motor vehicle accidents in patients with an implantable cardioverter defibrillator. AB - OBJECTIVES: This study was designed to examine driving safety in patients at risk for sudden death after implantation of a cardioverter-defibrillator. BACKGROUND: Cardioverter-defibrillators are frequently implanted in patients at high risk for sudden death. Despite concern about the safety of driving in these patients, little is known about their actual motor vehicle accident rates. METHODS: Surveys were sent to all 742 physicians in the United States involved in cardioverter defibrillator implantation and follow-up. Physicians were questioned about numbers of patients followed up, numbers of fatal and nonfatal accidents, physician recommendations to patients about driving and knowledge of state driving laws. RESULTS: Surveys were returned by 452 physicians (61%). A total of 30 motor vehicle accidents related to shocks from implantable defibrillators were reported by 25 physicians over a 12-year period from 1980 to 1992. Of these, nine were fatal accidents involving eight patients with a defibrillator and one passenger in a car driven by a patient. No bystanders were fatally injured. There were 21 nonfatal accidents involving 15 patients, 3 passengers and 3 bystanders. The estimated fatality rate for patients with a defibrillator, 7.5/100,000 patient-years, is significantly lower than that for the general population (18.4/100,000 patient-years, p < 0.05). The estimated injury rate, 17.6/100,000 patient-years, is also significantly lower than that for the general public (2,224/100,000 patient-years, p < 0.05). Only 10.5% (30 of 286) of all defibrillator discharges during driving resulted in accidents. Regarding physician recommendations, most physicians (58.1%) ask their patients to wait a mean (+/- SD) of 7.3 +/- 3.4 months after implantation or a shock before driving again. CONCLUSIONS: The motor vehicle accident rate caused by discharge from an implantable cardioverter-defibrillator is low. Although restricting driving for a short period of time after implantation may be appropriate, excessive restrictions or a total ban on driving appears to be unwarranted. PMID- 7797750 TI - Electrophysiologic characteristics of cells spanning the left ventricular wall of human heart: evidence for presence of M cells. AB - OBJECTIVES: The present work was designed to provide an initial characterization of M cells in the normal human heart. BACKGROUND: Recent studies have uncovered a unique population of cells in the midmyocardial region of the canine ventricle. These cells, named M cells, were found to possess electrophysiologic features and a pharmacologic responsiveness different from those of other myocardial cells. Although well characterized in the dog, their presence or absence in the human heart is unknown. METHODS: Standard microelectrode techniques were used to map slices of ventricular free wall obtained from normal human hearts (n = 4). Preparations were paced at cycle lengths ranging from 1 to 10 s. RESULTS: We identified three cell subtypes: endocardial, subepicardial (M cells) and epicardial cells. The principal features differentiating M cells from the other cell subtypes were their longer action potential duration, more accentuated action potential duration rate relations and greater maximal rate of increase in action potential upstroke (Vmax). Our findings suggest that M cells represent approximately 30% of the cellular mass of the left ventricular wall. Concordance between changes in their repolarization and changes in QTU interval provide support for the role of M cells in the generation of the electrocardiographic (ECG) U wave. CONCLUSIONS: This study provides evidence for the existence of M cells in the human heart that contribute to heterogeneity of repolarization within the ventricular wall. Our findings provide strong support for the hypothesis that M cells contribute importantly to the manifestation of the U wave on the ECG. PMID- 7797751 TI - The U wave and the M cell. PMID- 7797752 TI - Geometric changes allow normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy. AB - OBJECTIVES: This study of hypertensive left ventricular hypertrophy 1) assessed myocardial shortening in both the circumferential and long-axis planes, and 2) investigated the relation between geometry and systolic function. BACKGROUND: In hypertensive left ventricular hypertrophy, whole-heart studies have suggested normal systolic function on the basis of ejection fraction-systolic stress relations. By contrast, isolated muscle data show that contractility is depressed. It occurred to use that this discrepancy could be related to geometric factors (relative wall thickness). METHODS: We studied 43 patients with hypertensive left ventricular hypertrophy and normal ejection fraction (mean +/- SD 69 +/- 13%) and 50 clinically normal subjects. By echocardiography, percent myocardial shortening was measured in two orthogonal planes; circumferential shortening was measured at the endocardium and at the midwall, and long-axis shortening was derived from mitral annular motion (apical four-chamber view). Circumferential shortening was related to end-systolic circumferential stress and long-axis shortening to meridional stress. RESULTS: Endocardial circumferential shortening was higher than normal (42 +/- 10% vs. 37 +/- 5%, p < 0.01) and midwall circumferential shortening lower than normal in the left ventricular hypertrophy group (18 +/- 3% vs. 21 +/- 3%, p < 0.01). Differences between endocardial and midwall circumferential shortening are directly related to differences in relative wall thickness. Long-axis shortening was also depressed in the left ventricular hypertrophy group (18 +/- 6% in the left ventricular hypertrophy group, 21 +/- 5% in control subjects, p < 0.05). Midwall circumferential shortening and end-systolic circumferential stress relations in the normal group showed the expected inverse relation; those for approximately 33% of the left ventricular hypertrophy group were > 2 SD of normal relations, indicating depressed myocardial function. There was no significant relation between long-axis shortening and meridional stress, indicating that factors other than afterload influence shortening in this plane. CONCLUSIONS: High relative wall thickness allows preserved ejection fraction and normal circumferential shortening at the endocardium despite depressed myocardial shortening in two orthogonal planes. PMID- 7797753 TI - Chiari's network: normal anatomic variant or risk factor for arterial embolic events? AB - OBJECTIVES: This study was performed to assess the prevalence of Chiari's network in patients undergoing transesophageal echocardiography and to determine whether this anomaly is associated with other cardiac lesions or is characterized by typical clinical findings. BACKGROUND: Chiari's network is a congenital remnant of the right valve of the sinus venosus. It has been found in 1.3% to 4% of autopsy studies and is believed to be of little clinical consequence. METHODS: Video recordings of 1,436 consecutive adult patients evaluated by transesophageal echocardiography over a 30-month period were reviewed for the presence of Chiari's network. Echocardiographic contrast studies had been performed in all patients with Chiari's network and were compared with those of 160 consecutive patients without a Chiari net, serving as a control group. RESULTS: Chiari's network was present in 29 of 1,436 patients (prevalence 2%). A frequently associated finding was a patent foramen ovale in 24 (83%) of the 29 patients with Chiari's network versus 44 (28%) of 160 control patients (p < 0.001). Intense right-to-left shunting occurred significantly more often in patients with Chiari's network than in control patients (16 [55%] of 29 patients vs. 19 [12%] of 160 control patients, p < 0.001). Another frequent association was an atrial septal aneurysm in 7 (24%) of 29 patients. The indication for transesophageal echocardiography was a suspected cardiac source of arterial embolism in 24 (83%) of 29 patients with a Chiari net, 13 of whom (54%) had recurrent embolic events. Chiari's network was significantly more common in patients with unexplained arterial embolism than in patients evaluated for other indications (24 [4.6%] of 522 patients vs. 5 [0.5%] of 914 patients, p < 0.001). Potential causes for arterial embolism were present in 9 of the 24 patients with a Chiari net and embolic events (atrial septal aneurysm in 7, cerebrovascular lesion in 2). In 15 (62%) of 24 patients only a patent foramen ovale could be identified. Three patients had deep venous thrombosis and pulmonary embolism at the time of arterial embolism; none had a thrombus detected within the network. CONCLUSIONS: In patients undergoing transesophageal echocardiography, the prevalence of Chiari's network was 2%, which is consistent with autopsy studies. By maintaining an embryonic right atrial flow pattern into adult life and directing the blood from the inferior vena cava preferentially toward the interatrial septum, Chiari's network may favor persistence of a patent foramen ovale and formation of an atrial septal aneurysm and facilitate paradoxic embolism. PMID- 7797754 TI - Cardiac function in smokers and nonsmokers: the CARDIA study. The Coronary Artery Risk Development in Young Adults Study. AB - OBJECTIVES: This study assessed clinical and echocardiographic measures of cardiac function at rest in smokers and nonsmokers to determine the associations of cigarette smoking with various measures of left and right ventricular performance. BACKGROUND: Whereas the immediate cardiovascular effects of cigarette smoking have been well described, the long-term effects in an otherwise healthy cohort have not. Of particular interest were associations with heart rate, left ventricular end-systolic stress and left ventricular mass because higher levels of these measures would suggest increased myocardial oxygen consumption. METHODS: In year 5 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3,366 smokers and nonsmokers (ex-smokers were excluded) underwent echocardiography as well as assessment of heart rate, anthropometric measurements and blood pressure. Participants ranged in age from 23 to 35 years and were equally distributed by race and gender. Echocardiographic measures included pulsed Doppler pulmonary artery acceleration time (a decrease suggests increased pulmonary artery pressure), left ventricular mass, left ventricular end systolic stress and left ventricular fractional shortening. RESULTS: All comparisons were between smokers and nonsmokers. Heart rate at rest was significantly higher in smokers by 1.5 to 5 beats/min in all race/gender groups except black men. In men who smoked, pulmonary artery acceleration time was significantly lower by 4 to 8 ms. Except for black male smokers, there was a trend toward increased left ventricular mass (3 to 8 g) in all race/gender groups, significant in black women. Left ventricular end-systolic stress was significantly higher in women who smoked (4 to 6 dynes/cm2). There were no differences for systolic blood pressure or left ventricular fractional shortening. CONCLUSION: In an assessment of cardiovascular function at rest in young adults, quantifiable differences between smokers and nonsmokers that predict increased rest myocardial oxygen consumption in smokers were found. Some of these differences were gender specific. PMID- 7797755 TI - Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. AB - OBJECTIVES: This study was performed to assess a new indicator of regional left ventricular contraction determined by a two-dimensional tissue Doppler imaging technique. BACKGROUND: Recent studies have demonstrated that instantaneous tissue motion velocity can be noninvasively assessed by tissue Doppler imaging. However, quantitative assessment of regional left ventricular contraction is still difficult because of the effects of the Doppler angle of incidence and parallel motion of the whole heart. METHODS: We assessed left ventricular wall motion in 11 normal subjects, 14 patients with an old myocardial infarction (anteroseptal in 7, posterior in 7) and 8 patients with dilated cardiomyopathy. Tissue Doppler velocity was corrected by the Doppler angle of incidence after the hypothetical center of contraction was set. Subsequently, the myocardial velocity gradient between the endocardium and epicardium was determined from the velocity profile along each radial line from the center of contraction by using least squares linear regression. RESULTS: In normal subjects, peak myocardial velocity gradient was lower in the anteroseptal wall (mean [+/- SD] 1.69 +/- 0.53 s-1) than in the posterior wall (3.28 +/- 0.67 s-1, p < 0.01). Myocardial velocity gradient in the infarct regions was significantly lower (anteroseptal 0.58 +/- 0.41 s-1, p < 0.05; posterior 0.17 +/- 0.27 s-1, p < 0.01) than that in normal subjects as well as that in the corresponding noninfarct regions (2.84 +/- 0.37 s-1 and 1.48 +/- 0.25 s-1, p < 0.01, respectively). In patients with dilated cardiomyopathy, myocardial velocity gradient was generally lower (anteroseptal 0.72 +/- 0.59 s-1; posterior 0.93 +/- 0.67 s-1) than that in normal subjects (p < 0.01). CONCLUSIONS: These results demonstrate that regional left ventricular contraction can be quantitatively assessed by the myocardial velocity gradient derived from two-dimensional tissue Doppler imaging. We suggest that myocardial velocity gradient has potential for the quantitative assessment of regional left ventricular contraction abnormalities in patients. PMID- 7797756 TI - Left ventricular blood flow patterns in normal subjects: a quantitative analysis by three-dimensional magnetic resonance velocity mapping. AB - OBJECTIVES: Magnetic resonance velocity mapping was used to investigate the hypothesis of a vortex motion within the left ventricle interacting with mitral valve motion and inflow velocity. BACKGROUND: In vitro flow visualization studies have suggested the presence of a large anterior vortex inside the left ventricle during mitral inflow. However, to our knowledge the occurrence of this phenomenon has not been demonstrated in the human left ventricle. METHODS: Magnetic resonance velocity mapping was performed in 26 healthy volunteers using a flow adjusted gradient sequence for three-dimensional flow velocity acquisition in the long-axis plane of the left ventricle. By computer processing, the flow vectors in the left ventricle were visualized and animated dynamically. RESULTS: The early diastolic mitral inflow was apically directed, and a large counterclockwise anterior vortex was created within the left ventricle shortly after the onset of the mid-diastolic semiclosure of the anterior mitral leaflet. During mid diastolic diastasis, mitral inflow ceased until the flow accelerated again at atrial systole. The final closure of the mitral valve was preceded by a smaller vortex seen at the tips of the mitral leaflets. At systolic ejection, all flow vectors were directed toward the left ventricular outflow tract. The anterior vortex had a radius of 1.62 +/- 0.24 cm (mean +/- SD), and the average angular velocity (i.e., the rotation of an element about the center of the vortex within the central core) was 30.08 +/- 9.98 radians/s. The maximal kinetic energy of the anterior vortex was 4.3 x 10(-4) +/- 7.1 x 10(-5) J. CONCLUSIONS: The hypothesis of a diastolic vortex formation in the human left ventricle was confirmed, and its close temporal relation to the motion of the anterior mitral leaflet was demonstrated. PMID- 7797757 TI - Simultaneous measurement of pulmonary venous flow by intravascular catheter Doppler velocimetry and transesophageal Doppler echocardiography: relation to left atrial pressure and left atrial and left ventricular function. AB - OBJECTIVES: The aim of our study was to compare measurements of pulmonary venous flow velocity obtained either by transesophageal Doppler echocardiography or by intravascular catheter Doppler velocimetry. Furthermore, the relation among pulmonary venous flow velocity, left atrial compliance and left atrial pressure was evaluated. BACKGROUND: Data about the relation between left atrial pressure and pulmonary venous flow velocity are controversial. METHODS: A total of 32 patients undergoing elective open heart surgery for coronary artery bypass grafting were included prospectively in the study. Pulmonary venous flow velocity (Doppler catheter) and left atrial pressure (microtip pressure transducer) were recorded simultaneously with recordings of pulmonary venous flow velocity obtained by transesophageal Doppler echocardiography. RESULTS: Agreement between Doppler catheter and Doppler echocardiographic measurements of pulmonary venous flow velocity (n = 18 patients) was analyzed using the Bland-Altmann technique. The 95% limits of agreement were -0.16 to +0.11 m/s for systolic peak velocity, 0.14 to +0.09 m/s for diastolic peak velocity and -0.12 to +0.10 m/s for atrial peak velocity. The closest agreement between both methods was found for the ratio of systolic to diastolic peak velocity, the ratio of systolic to diastolic flow duration and the time from Q deflection on the electrocardiogram to maximal flow velocity. Mean left atrial pressure was strongly correlated with the ratio of systolic to diastolic peak velocity (r = -0.829), systolic velocity-time integral (r = -0.653), time to maximal flow velocity (r = 0.844) and the ratio of systolic to diastolic flow duration (r = -0.556). The ratio of systolic to diastolic peak velocity and the time to maximal flow velocity were identified as strong independent predictors of mean left atrial pressure. Left atrial compliance was not found to be an independent predictor of mean left atrial pressure. CONCLUSIONS: Flow velocity in the left upper pulmonary vein can be reliably recorded by transesophageal pulsed wave Doppler echocardiography. Our data reveal further evidence that mean left atrial pressure can be estimated by the pattern of pulmonary venous flow velocity. PMID- 7797758 TI - Evolution of coronary artery pattern according to short-axis aortopulmonary rotation: a new categorization for complete transposition of the great arteries. AB - OBJECTIVES: We studied the correlation between coronary artery pattern and aortopulmonary rotation in complete transposition of the great arteries. BACKGROUND: Classifications of the coronary arteries in complete transposition are puzzling and incomplete. METHODS: Coronary artery anatomy and relation of the great arteries were identified at angiography, echocardiography, surgical intervention or autopsy in 76 patients with complete transposition from 1988 to 1993. Five main types (type 0 and Shaher types 1,2,4 and 9) and their similar variants of epicardial configuration were categorized into five patterns (O, I, II, IV and IX). In addition, data from 568 cases from published reports were collected for analysis. RESULTS: As the aorta rotated from a left anterior to a directly anterior location relative to the pulmonary trunk, the left anterior descending coronary artery arose from the left-hand sinus together with the right coronary artery (type 0, one case decreased to no cases); then it gradually shifted to the left to have the same origin as the left circumflex coronary artery from the right-hand sinus (type 1, 10 cases increased to 146, p < 0.0003). When the aorta rotated farther clockwise from directly anterior to right anterior (type 1, 146 cases increased to 235; type 2, 9 cases increased to 50, p < 0.0006) or from right anterior to right lateral (type 1, 235 cases decreased to 6 cases; type 2, 50 cases decreased to 20, p < 0.00000), the left circumflex coronary artery tended to move retropulmonically and originated from the left-hand sinus with the right coronary artery (type 2). When the aorta moved from right anterior to right lateral (type 2, 50 cases decreased to 20; type 4, 13 cases increased to 14, p < 0.031) or from right lateral to right posterior (type 2, 20 cases decreased to 1; type 4, 14 cases increased to 16, p < 0.0003), the right coronary artery shifted to the right-hand sinus anteaortically to join the left anterior descending coronary artery (type 4). Finally, the left anterior descending coronary artery combined with the left circumflex coronary artery (type 9, 12 cases increased to 21, p = 0.407) to become the usual pattern for normally related great arteries. Eta-square analysis showed that the evolution from pattern O to IX was dependent on clockwise aortopulmonary rotation. CONCLUSIONS: The coronary arteries in complete transposition of the great arteries can be classified into five patterns and their evolution deduced on the basis of aortopulmonary rotation. Dependence of coronary artery type on aortopulmonary rotation made it possible to anticipate the coronary pattern from the relation of the great arteries in transposition. PMID- 7797760 TI - Enhanced detection of myocardial ischemia by stress dobutamine echocardiography utilizing the "biphasic" response of wall thickening during low and high dose dobutamine infusion. AB - OBJECTIVES: We sought to assess the ability of the "biphasic" response (i.e., initial improvement in wall thickening followed by reduced wall thickening) during serial dobutamine stress echocardiography to detect ischemia in patients with a wall motion abnormality. Furthermore, we compared the power of the biphasic echocardiographic response with that of myocardial perfusion imaging for the detection of myocardial ischemia. BACKGROUND: Stress echocardiography has been shown to be less sensitive than radionuclide perfusion imaging for detecting ischemia in patients with a wall motion abnormality. Peak stress wall thickening in such areas may not give a full account of the intermediate changes, whereas initial improvement (the biphasic response) may enhance diagnosis. METHODS: Patients with a wall motion abnormality and documented coronary artery disease underwent simultaneous graded dobutamine (5 to 40 micrograms/kg body weight per min) stress echocardiography and radionuclide perfusion imaging with single photon emission computed tomography using either technetium-99m sestamibi or technetium-99m tetrofosmin. Semiquantitative analyses of image groups were performed in blinded manner by two separate groups of observers. RESULTS: Myocardial ischemia was detected by perfusion imaging in 45 of the 54 patients. High dose dobutamine echocardiography detected ischemia in only 25 (56%) of these patients. However, when the biphasic response was taken into account, ischemia was detected in 44 (98%) of the 45 patients (p < 0.001). Agreement between radionuclide imaging and echocardiographic findings for the detection of ischemia was significantly enhanced (p = 0.03) when the biphasic response was used (89%, kappa = 0.51) instead of high dose stress dobutamine echocardiography (56%, kappa = 0.10). CONCLUSIONS: The detection of myocardial ischemia may be significantly enhanced by utilizing the biphasic response during serial stress dobutamine echocardiography in patients with a wall motion abnormality. PMID- 7797759 TI - Effect of late postoperative atrial septal defect closure on hemodynamic function in patients with a Lateral tunnel Fontan procedure. AB - OBJECTIVES: The aim of this study was to evaluate prospectively the effect of late atrial septal defect closure on cardiac output and oxygen delivery in patients who have undergone the Fontan procedure. BACKGROUND: An adjustable atrial septal defect is incorporated in patients undergoing the Fontan procedure who have increased pulmonary vascular resistance or poor ventricular function, or both. After the Fontan procedure, the atrial septal defect is test occluded. Patients with mean right atrial and pulmonary artery pressures > 15 mm Hg are discharged with the atrial septal defect open. METHODS: Twelve patients (20 months to 12 years old) underwent evaluation and closure of the atrial septal defect at a mean interval of 3.8 months (range 1 to 18) after the Fontan procedure. Each patient underwent full right and left heart catheterization. Cardiac output was obtained using the cine-volume method. The study included six patients with a high transpulmonary gradient or poor ventricular function preoperatively, or both (high risk group) and six who had only borderline increased pulmonary vascular resistance (low risk group). Patients in both groups had a mean right atrial pressure > 15 mm Hg when the atrial defect was test occluded in the first week after the Fontan procedure. RESULTS: All results are given as mean value +/- SD. Ventricular end-diastolic pressure was significantly lower (p = 0.03) with the atrial septal defect open in low risk patients (6 +/- 3 mm Hg) than in high risk patients (10 +/- 3 mm Hg). With the atrial septal defect open, low risk patients had a significantly higher (p = 0.04) cardiac index (4.87 +/- 0.81 liters/min per m2) than the high risk patients (3.96 +/- 0.47 liters/min per m2). There was no significant difference (p = 0.14) in cardiac index between the two groups with occlusion of the atrial septal defect. Oxygen delivery was also significantly higher (p < 0.05) with the atrial septal defect open in low risk patients (836 +/- 99 ml/min per m2) than in high risk patients (704 +/- 106 ml/min per m2). There was no significant difference (p = 0.89) in oxygen delivery between the two groups with occlusion of the atrial septal defect. With the atrial septal defect open, the interatrial gradient was not significantly different in low risk patients (4 +/- 1 mm Hg) from that in high risk patients (4 +/- 1 mm Hg). CONCLUSIONS: These data show that an interatrial communication results in increased postoperative systemic perfusion and oxygen delivery in patients with good diastolic ventricular function after the Fontan procedure. PMID- 7797761 TI - Incidence of aneurysm formation after Dacron patch aortoplasty repair for coarctation of the aorta: long-term results and assessment utilizing magnetic resonance angiography with three-dimensional surface rendering. AB - OBJECTIVES: Magnetic resonance angiography with three-dimensional surface rendering was performed to determine its value in assessing anatomic detail in patients with suspected aortic aneurysms. BACKGROUND: Dacron patch aortoplasty repair of coarctation of the aorta carries an inherent risk of aneurysm development. Sudden death from aortic rupture prompted discontinuing this operation and evaluating 39 patients (16 girls; mean age 6.3 years, range 10 days to 14.5 years) undergoing repair between January 1976 and October 1987. The aorta ruptured in 10 patients; 6 died at a mean interval of 8.1 years (range 0.75 to 12.4) after repair. All 33 survivors were interviewed and examined. METHODS: Conventional magnetic resonance imaging was performed in 26 patients, magnetic resonance angiography in 18. Angiographic slices were used to reconstruct three dimensional images. No catheterization or contrast angiography was performed. Surgical intervention was based on clinical findings and magnetic resonance images. RESULTS: Twenty patients (11 girls) developed aneurysms, of which nine were detected in patients studied by magnetic resonance. Ruptures occurred in eight female patients, three of whom were pregnant. Surface renderings accurately defined aortic anatomy or aneurysms in all patients. On follow-up, no aneurysms have been detected in patients with negative magnetic resonance study results. Precise anatomic correlation with operative findings was reported. CONCLUSIONS: Magnetic resonance angiography with three-dimensional surface rendering provides noninvasive, radiation-free and contrast agent-free high resolution images of the thoracic aorta. These images can be reviewed and have three-dimensional form and perspective. These techniques were preferred over invasive angiography by surgeons and clinicians as definitive, risk-free procedures before surgical intervention. PMID- 7797762 TI - Evaluation of pulmonary artery histopathologic findings in congenital heart disease: an in vitro study using intravascular ultrasound imaging. AB - OBJECTIVES: This study aimed to 1) compare in vitro intravascular ultrasound images of human pulmonary arteries with corresponding histologic sections, and 2) correlate the relation between intravascular ultrasound findings and Heath Edwards pathologic grade of pulmonary vascular changes. BACKGROUND: The pathologic assessment of the pulmonary vascular bed is essential for diagnosis and management of congenital heart disease with pulmonary hypertension. METHODS: We evaluated and compared intravascular ultrasound images with histologic findings at identical sites in 40 pulmonary artery segments from 17 autopsy studies: group 1 = 7 patients with pulmonary hypertension (Heath-Edwards grade I to V, 20 segments); group 2 = 10 patients without cardiopulmonary disease (20 segments). RESULTS: In group 2, the pulmonary artery wall echo consisted of a single layer. In group 1, 1) all segments of pulmonary arteries from patients with pulmonary hypertension showed a three-layered appearance; 2) in patients with mild pulmonary hypertension (Heath-Edwards grades I and II), intravascular ultrasound demonstrated increased thickness of the echoluscent zone due to medial hypertrophy with no intimal reaction; 3) patients with severe pulmonary hypertension (Health-Edwards grade III or higher) had intravascular ultrasound findings of increased medial thickness and a bright inner layer from intimal hyperplasia; 4) percent wall thickness derived from intravascular ultrasound showed a significant correlation with that determined by histologic examination (r = 0.89, p = 0.0001, n = 20). CONCLUSIONS: Changes observed with intravascular ultrasound imaging correlate well with histopathologic grade. Thus, intravascular ultrasound may have significant utility in the evaluation of pulmonary vascular morphology in patients with pulmonary hypertension. PMID- 7797763 TI - Idiopathic atrial fibrillation in dogs: electrophysiologic determinants and mechanisms of antiarrhythmic action of flecainide. AB - OBJECTIVES: This study sought to determine the mechanisms of idiopathic atrial fibrillation and the atrial antifibrillatory action of flecainide in dogs. BACKGROUND: In a small subset of dogs, sustained atrial fibrillation can be readily induced in the absence of vagal tone. The electrophysiologic mechanisms underlying this ability to sustain atrial fibrillation, and of flecainide action on the arrhythmia, are unknown. METHODS: Six dogs with inducible sustained atrial fibrillation were studied before and after flecainide administration and compared with a control group of 10 dogs. RESULTS: Dogs with atrial fibrillation differed in displaying more shortening of the atrial refractory period with increased rate, resulting in a significantly shorter refractory period and wavelength for reentry at rapid rates, and in increased regional dispersion in refractoriness. Activation maps during sustained fibrillation showed a mean (+/- SE) of 6.3 +/- 0.4 coexistent zones of reentry, compatible with short wavelengths, whereas in control dogs activation during self-limited atrial fibrillation was better organized, and the number of reentrant circuits was smaller. Quantitative analysis demonstrated significantly greater inhomogeneity of activation during atrial fibrillation in dogs with atrial fibrillation than in control animals. Flecainide terminated atrial fibrillation by increasing the duration and homogeneity of atrial refractoriness at rapid rates, thereby reducing the number of reentry circuits and the heterogeneity of activation. CONCLUSIONS: The ability of atrial fibrillation to sustain itself resulted from enhanced rate-dependent shortening of atrial refractoriness and increased regional heterogeneity. Flecainide reversed these changes and restored sinus rhythm. These results suggest potential mechanisms of idiopathic atrial fibrillation and are pertinent to understanding the clinical actions of flecainide. PMID- 7797765 TI - President's page: expanding the role of the American College of Cardiology. PMID- 7797764 TI - The decline of the doctor-patient relationship. PMID- 7797766 TI - American Heart Association consensus panel statement on preventing heart attack and death in patients with coronary disease. PMID- 7797767 TI - AHA consensus panel statement. Preventing heart attack and death in patients with coronary disease. The Secondary Prevention Panel. PMID- 7797768 TI - Giant cell myocarditis study group. PMID- 7797769 TI - Guidelines for training in adult cardiovascular medicine. PMID- 7797770 TI - Coagulation activity is increased in the left atrium of patients with mitral stenosis. PMID- 7797771 TI - Coagulation activity is increased in the left atrium of patients with mitral stenosis. PMID- 7797772 TI - Methodology of quantitating intracoronary ultrasound. PMID- 7797773 TI - Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropropane-exposed sonicated dextrose albumin. AB - OBJECTIVES: The purpose of this study was to determine whether intravenous dextrose albumin sonicated with a commonly used gas of low blood solubility and diffusivity (perfluoropropane) could identify acute myocardial ischemia and reperfusion. BACKGROUND: Recently, it has been demonstrated that dextrose albumin sonicated with gases that have low blood solubility and diffusivity results in microbubbles capable of consistently producing myocardial ultrasound contrast after intravenous injection. It remains to be determined, however, whether this contrast agent can visually detect the myocardial blood flow abnormalities seen with acute ischemia or stunned myocardium after reperfusion. METHODS: We gave intravenous injections (0.06 ml/kg body weight) of perfluoropropane-exposed sonicated dextrose albumin to 10 open chest dogs. The measured degree of myocardial contrast (0+ to 2+) and background-subtracted peak anterior myocardial videointensity produced from each injection were measured at three stages: 1) under baseline conditions, 2) during acute ischemia produced by a proximal left anterior descending coronary artery ligation lasting 10 to 120 min, and 3) after reflow was established. Coronary blood flow was monitored during all injections by using an ultrasound flow probe placed around the left anterior descending artery. RESULTS: Coronary blood flow ranged from 0 to 137 ml/min, and peak myocardial videointensity after intravenous administration of perfluoropropane exposed sonicated dextrose albumin ranged from 0 to 70 gray scale U. There was consistent visual myocardial opacification in all dogs during baseline conditions and a visually evident decrease in myocardial contrast in the left anterior descending artery distribution after ligation. A relative increase in contrast in this same distribution after intravenous contrast agent administration occurred in 7 of the 10 dogs during reflow. Quantitatively, there was an excellent correlation in individual dogs between peak myocardial videointensity and coronary flow at all stages (mean correlation coefficient 0.95 +/- 0.04, range 0.87 to 0.99). CONCLUSIONS: Perfluoropropane-exposed sonicated dextrose albumin is an ultrasound contrast agent that can visually identify myocardial perfusion abnormalities from a peripheral venous injection. PMID- 7797774 TI - Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasound. AB - OBJECTIVES: The purpose of this study was to use intravascular ultrasound to determine the morphologic appearance of the coronary arteries, relating the absence, presence and extent of atherosclerosis to the response of the coronary arteries to acetylcholine infusion. BACKGROUND: Endothelial function plays a major role in the pathophysiology of myocardial ischemia and angina pectoris. The response of the coronary arteries to selective infusion of acetylcholine has been used to examine endothelial function, with vasoconstriction occurring in the absence of intact endothelial function. Vasoconstriction to acetylcholine infusion in humans without overt coronary artery disease has been attributed to early atherosclerosis not detected by coronary angiography. METHODS: Twenty-nine patients without overt coronary artery disease underwent selective coronary angiography and selective intracoronary infusion of increasing concentrations of acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter), followed by intravascular ultrasound imaging. RESULTS: The response of the coronary arteries to acetylcholine infusion was not dependent on the absence or presence of atherosclerotic plaque, as detected by intravascular ultrasound. The percent change in epicardial coronary artery diameter during acetylcholine infusion versus baseline was -14 +/- 28% (mean +/- SD) in the seven patients with no visible atherosclerosis on intravascular ultrasound versus -9 +/- 20% in the 22 patients with visible atherosclerosis on intravascular ultrasound (p = NS, confidence interval -14% to 25%). There was a greater vasoconstrictive response to acetylcholine infusion in patients with risk factors for coronary artery disease than in those without risk factors (p = 0.003). CONCLUSIONS: The vasoreactive response to acetylcholine is not necessarily dependent on ultrasound detection of the presence or absence of atherosclerosis. PMID- 7797775 TI - Absence of vascular tolerance in conductance vessels after 48 hours of intravenous nitroglycerin in patients with coronary artery disease. AB - OBJECTIVES: We examined whether reflex neurohormonal constrictor forces attenuate the vasodilator action of nitroglycerin on large peripheral conductance vessels. BACKGROUND: Continuous nitroglycerin therapy is associated with the development of early tolerance with respect to its hemodynamic effects. It remains to be demonstrated whether vascular tolerance of large conductance vessels is an important contributory factor. METHODS: Radial artery diameter and forearm blood flow velocity were measured before and 24 and 48 h after continuous intravenous nitroglycerin infusion (0.5 microgram/kg body weight per min) in 10 patients with coronary artery disease (mean age +/- SEM 59 +/- 4 years) by using a high resolution ultrasound device. Blood flow (ml/min) was calculated from mean blood flow velocity and cross-sectional area. RESULTS: Increasing concentrations of nitroglycerin led to a dose-dependent increase in radial artery diameter (maximal +24 +/- 2%) and heart rate. Forearm vascular resistance and forearm blood flow were unchanged. After 24 and 48 h of treatment, additional nitroglycerin did not further increase radial artery diameter, indicating that the nitroglycerin induced dilation of the radial artery was maintained and was still maximal. In addition, radial artery diameter measured before and after 48 h of nitroglycerin infusion and after withdrawal of nitroglycerin in five additional patients showed that, after withdrawal, arterial diameter returned to baseline values within 35 min. Plasma renin activity and serum aldosterone and vasopressin levels increased significantly at 24 and 48 h, accompanied by a decrease in hematocrit. CONCLUSIONS: Continuous intravenous administration of nitroglycerin exerts a sustained vasodilator effect for 48 h in large conductance vessels. Neurohormonal activation and compensatory intravascular volume expansion do not attenuate the vasodilator effects of nitroglycerin on peripheral conductance vessels during the 1st 48 h of treatment. PMID- 7797777 TI - Implications of recurrent ischemia after reperfusion therapy in acute myocardial infarction: a comparison of thrombolytic therapy and primary angioplasty. AB - OBJECTIVES: The purpose of this study was to examine the incidence and implications of recurrent ischemia after different reperfusion strategies in acute myocardial infarction. BACKGROUND: The rates and effects of recurrent ischemia after reperfusion with thrombolytic therapy and with primary percutaneous transluminal coronary angioplasty have not been compared. METHODS: At 12 centers 395 patients presenting within 12 h of the onset of acute myocardial infarction were prospectively randomized to receive recombinant tissue type plasminogen activator (rt-PA) or primary coronary angioplasty. Sixteen clinical variables were examined by using univariate and multiple logistic regression analysis to identify the predictors of recurrent ischemia. The relation of recurrent ischemic events to patient outcome was analyzed. RESULTS: Recurrent ischemia developed in 76 patients (19.2%) before hospital discharge, resulting in reinfarction in 18 patients (4.6%) and death in 5 (2.6%). Recurrent ischemia occurred in 56 patients (28.0%) after rt-PA but in only 20 patients (10.3%) after coronary angioplasty (p < 0.0001), directly contributing to a higher rate of death or reinfarction (7.5% vs. 3.1%, p = 0.05), catheterization and revascularization procedures and prolonged hospital stay after thrombolysis. By multivariate analysis, treatment with coronary angioplasty rather than rt-PA was the strongest predictor of freedom from recurrent ischemia. Although the incidence of recurrent ischemia after angioplasty and after rt-PA was similar within the 1st 2 days of admission (9.2% vs. 14.5%, p = 0.11), after hospital day 2 recurrent ischemia occurred in only 2 patients who received primary angioplasty compared with 27 patients who received rt-PA (1.1% vs. 13.5%, p < 0.0001). CONCLUSIONS: The development of recurrent ischemia adversely affects patient outcome, increasing morbidity, mortality and resource utilization. The much lower rate of recurrent ischemia after primary coronary angioplasty than after rt-PA results in improved survival without reinfarction and allows a shorter, less complicated hospital stay. Given the extremely low rate of recurrent ischemia after hospital day 2, safe early discharge on day 3 after primary coronary angioplasty should be feasible in selected patients with acute myocardial infarction. PMID- 7797778 TI - Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group. AB - OBJECTIVES: This study sought to determine the prognostic value of rest and exercise left ventricular ejection fraction in patients receiving thrombolytic therapy as part of the Thrombolysis in Myocardial Infarction (TIMI) trial. BACKGROUND: In the prethrombolytic era, ejection fraction at rest as well as during exercise was an important prognostic index in patients recovering from acute myocardial infarction. The prognostic value of these measurements in the thrombolytic era is not clear. METHODS: As part of the TIMI II protocol, we obtained radionuclide left ventricular ejection fraction at rest and during symptom-limited submaximal supine exercise. Measurements were related to 1-year all-cause as well as cardiac mortality. In addition, the relation between ejection fraction obtained at rest and 1-year cardiac mortality in this study was compared with the relation established previously in the prethrombolytic era by the Multicenter Postinfarction Research Group. RESULTS: A distinct relation was noted between left ventricular ejection fraction at rest and all-cause mortality. The highest mortality rate (9.9%) was noted in patients with an ejection fraction < 30%. Those not undergoing a study had a 1-year mortality rate of 6.2%. Peak exercise ejection fraction provided prognostic information similar to that of rest ejection fraction. Likewise, change in ejection fraction from rest to exercise did not appreciably improve prognostic impact. CONCLUSIONS: Rest left ventricular ejection fraction is an important prognostic index in patients receiving thrombolytic therapy. Peak exercise ejection fraction and the change in ejection fraction from rest to exercise do not provide appreciable prognostic data beyond those obtained at rest. Patients unable to exercise or those not having a rest study have a poor prognosis. When compared with the Multicenter Postinfarction Research Group data, there was strong evidence of a difference in survival in the two studies. At any level of ejection fraction, mortality was lower in TIMI II patients than in patients in the prethrombolytic era. PMID- 7797776 TI - Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. AB - OBJECTIVES: We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND: Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS: A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS: The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction. PMID- 7797780 TI - Differential localization of atrial natriuretic peptide and skeletal alpha-actin messenger RNAs in left ventricular myocytes of patients with dilated cardiomyopathy. AB - OBJECTIVES: This study was designed to determine whether atrial natriuretic peptide and skeletal alpha-actin messenger RNAs (mRNAs) are co-localized in ventricular myocytes of patients with dilated cardiomyopathy. BACKGROUND: Atrial natriuretic peptide and skeletal alpha-actin are known as augmented genes with cardiac hypertrophy. However, the expression and localization of both genes in chronic failing heart remain unclear. METHODS: Left ventricular biopsy specimens were obtained from 14 patients with dilated cardiomyopathy. Atrial natriuretic peptide and skeletal alpha-actin mRNAs were detected by in situ hybridization with specific sulfur-35 uridine triphosphate-labeled RNA probes in the serial sections. RESULTS: Atrial natriuretic peptide mRNA was detected in 10 patients, and intense signals were localized in the myocytes located in the subendocardium and around the interstitial fibrous area. By contrast, skeletal alpha-actin mRNA was homogeneously detected in all myocytes in seven patients. By left ventriculography, patients with skeletal alpha-actin-positive findings had a lower ejection fraction (37.1 +/- 6.0%) than those with negative findings (46.3 +/- 5.8%, p < 0.05), but atrial natriuretic peptide mRNA expression was not related to left ventricular function. CONCLUSIONS: These results indicate that the expression of atrial natriuretic peptide and skeletal alpha-actin mRNAs are not always co-localized in the left ventricle of patients with dilated cardiomyopathy and suggest that the mechanisms of the regulation of these two genes in the chronic failing heart are different. PMID- 7797781 TI - Economic outcomes of withdrawal of digoxin therapy in adult patients with stable congestive heart failure. AB - OBJECTIVES: This study sought to analyze the health and economic outcomes of withdrawal of digoxin therapy among U.S. adult patients with stable congestive heart failure. BACKGROUND: New information regarding the outcomes of digoxin withdrawal has been provided by the Prospective Randomized Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trials. We interpreted and extrapolated the results of these trials to describe implications on a national level. METHODS: We used a decision-analytic model to estimate the outcomes of two alternative strategies to 1) continue and 2) withdraw digoxin in patients with congestive heart failure with normal sinus rhythm, New York Heart Association functional class II or III and left ventricular ejection fraction < or = 35%. Epidemiologic assumptions were derived from published reports and expert opinion. Assumptions regarding the effectiveness of digoxin therapy were derived from the RADIANCE and PROVED digoxin withdrawal trials. Hospital and Medicare data were used for economic assumptions. Calculated outcomes included treatment failures, cases of digoxin toxicity and health care costs. RESULTS: The continuation of digoxin therapy in these patients with congestive heart failure nationally would avoid an estimated 185,000 clinic visits, 27,000 emergency visits and 137,000 hospital admissions for congestive heart failure. After accounting for an estimated 12,500 cases of digoxin toxicity, the net annual savings would be $406 million, with a 90% range of uncertainty of $106 to $822 million. One-way sensitivity analysis indicated that digoxin therapy is cost-saving when the assumed annual incidence of digoxin toxicity is < or = 33%. CONCLUSIONS: The continuation of digoxin therapy in patients with stable congestive heart failure should be strongly considered, because this strategy is likely to lead to both lower costs and greater health benefits on the basis of available information. PMID- 7797782 TI - A one-year perspective on MedWatch: the Food and Drug Administration's new medical products reporting program. PMID- 7797779 TI - Long-term outcome of patients with biopsy-proved myocarditis: comparison with idiopathic dilated cardiomyopathy. AB - OBJECTIVES: The study objectives were 1) to assess the long-term outcome of patients with biopsy-proved lymphocytic myocarditis (Dallas criteria), and 2) to compare the outcome of these patients with that of patients with idiopathic dilated cardiomyopathy. BACKGROUND: Endomyocardial biopsy is frequently performed in patients presenting with dilated cardiomyopathy to identify lymphocytic myocarditis. Most previous studies of the natural history of myocarditis were performed before the establishment of the Dallas criteria. Thus, it is important to evaluate the prognostic value of positive endomyocardial biopsy findings in patients presenting with dilated cardiomyopathy, using standardized criteria for lymphocytic myocarditis. METHODS: All endomyocardial biopsy results from the Mayo Clinic (October 1979 to April 1988) with a diagnosis of myocarditis were reclassified according to the Dallas criteria. Patients whose biopsy specimens showed borderline or lymphocytic myocarditis were included in the study group; those with systemic inflammatory diseases known to be associated with myocardial involvement were excluded. Study group survival was compared with that for a cohort of patients with idiopathic dilated cardiomyopathy seen at the Mayo Clinic from 1976 to 1987 who had endomyocardial biopsy findings negative for myocarditis. RESULTS: Biopsy specimens from 41 patients met the Dallas criteria for a diagnosis of myocarditis (n = 28) or borderline myocarditis (n = 13). Of these 41 patients, 9 were excluded because of the presence of systemic diseases known to be associated with myocarditis, and 5 patients were excluded because of lack of available follow-up data. The myocarditis study group therefore included 27 patients (10 with borderline myocarditis, 17 with myocarditis). Fifty-eight patients with a diagnosis of idiopathic dilated cardiomyopathy who underwent endomyocardial biopsy served as the comparison cohort. Ejection fraction was lower in patients with idiopathic dilated cardiomyopathy ([mean +/- SD] 25 +/- 11%) than in those with myocarditis (38 +/- 19%, p = 0.001), even though a higher proportion of myocarditis group patients were in New York Heart Association functional class III or IV (63%) than patients in the dilated cardiomyopathy group (30%, p = 0.005). There was no difference in 5-year survival rate between the myocarditis and idiopathic dilated cardiomyopathy groups (56% vs. 54%, respectively). CONCLUSIONS: This study demonstrates that the long-term outcome of patients with biopsy-proved myocarditis seen in a referral setting is poor, although no different from that of patients with idiopathic dilated cardiomyopathy. With the current lack of proved effective treatment for lymphocytic myocarditis and no demonstration of survival benefit for patients with myocarditis, these data suggest that endomyocardial biopsy performed to exclude myocarditis is of limited prognostic value in the routine evaluation of dilated cardiomyopathy. PMID- 7797783 TI - Indoor allergen levels in day nurseries. AB - BACKGROUND: Because allergic sensitization seems to occur especially during infancy, we decided to evaluate such an exposure in day nurseries. METHODS: Thirty day nurseries in Marseilles, which were selected at random, were visited during 2 weeks in April 1993. Routine cleaning includes daily cleaning of smooth floors, weekly laundering of sheets, and monthly cleaning of soft toys. Mattresses are encased in synthetic covers. Dust samples were collected from four settings: infants' mattresses and pillows, smooth floors, and soft toys. Levels of mite, cockroach, cat, and dog allergens were analyzed with a monoclonal antibody-based ELISA. RESULTS: Mite allergen levels were lower than the proposed threshold level for sensitization (2 micrograms/gm of dust) on 94% of mattresses and soft toys and on 100% of floors and pillows. Cat allergen levels in mattresses ranged from less than 0.1 to 4.5 micrograms/gm dust. On floors, cat allergen levels ranged from less than 0.1 to 2.4 micrograms/gm dust. Only 10% of pillows and soft toys had levels greater than 2 micrograms/gm of dust. Fel d I levels were significantly higher (p < 0.03) in mattresses from nurseries with curtains and were correlated with the percentage of children with a cat at home. In almost all day nurseries, cockroach allergen (Bla g I and Bla g II) levels were very low. Only three samples from mattresses had dog allergen levels greater than 2 micrograms of Can f I allergen per gram of dust. On floors the level was always lower than 2 micrograms/gm. CONCLUSIONS: These data clearly show that indoor allergen levels are much lower in day nurseries than in most houses. Most samples contain allergen levels below threshold levels for sensitization. Thus children of atopic parents are less likely to become sensitized to indoor allergens in day nurseries than in their own homes. In addition, this study emphasizes the efficacy of avoidance measures such as use of synthetic protective mattress covers, frequent washing of sheets and soft toys, and avoidance of carpets and curtains. PMID- 7797784 TI - Cat shedding of Fel d I is not reduced by washings, Allerpet-C spray, or acepromazine. AB - BACKGROUND: No published studies have compared the effectiveness of several treatments proposed to reduce cat allergenicity. Cat washing studies demonstrating efficacy involved very small sample sizes or infrequent washings. Allerpet-C (Allerpet, Inc., New York, N.Y.), a widely advertised topical spray, and acepromazine, a tranquilizer advocated as efficacious in subsedating doses, have never been scientifically studied. OBJECTIVE: We compared the effects of cat washing, Allerpet-C spray, and acepromazine with that of no treatment on the shedding of the primary cat allergen, Felis domesticus I by cats. METHODS: In a blinded, comparative, controlled study, we measured the amounts of Fel d I shed during an 8-week treatment period with a sample of 24 female mongrel cats randomly assigned to four groups; one group received weekly distilled water washings, one received weekly Allerpet-C spray applications, one received daily oral acepromazine, and one had no treatment (control). Thirty-minute, twice weekly air samples were collected from each cat with a laminated plastic-acrylic chamber and air sampler. RESULTS: One-sample, two-sided t tests comparing baseline to final-week measurements revealed no significant change in Fel d I within each group (mean change +/- SD: washing; 487.6 +/- 1896.4 mU per 30 minutes, p = 0.63; Allerpet-C spray, 429.2 +/- 871.6 mU per 30 minutes, p = 0.46 acepromazine; -620.6 +/- 1031.2, p = 0.52 per 30 minutes). Furthermore, analysis of covariance revealed no significant change in Fel d I levels between groups (p = 0.72). CONCLUSIONS: Out data do not show significant reductions in Fel d I shedding as a result of any of these treatments. Therefore we cannot recommend them to patients allergic to cats. PMID- 7797785 TI - Chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. AB - BACKGROUND: Studies in asthma with systemic corticosteroids given at 3:00 PM have shown a superior therapeutic benefit compared with dosing at other time points. OBJECTIVE: The study was designed to compare beneficial and systemic effects of 800 micrograms of inhaled triamcinolone once daily at 3:00 PM (QD group) versus 200 micrograms conventional four times a day dosing (QID group). METHODS: Efficacy outcome measures included forced expiratory volume in 1 second (FEV1), peak expiratory flow rates, bronchial responsiveness, and use of beta-agonist. Systemic effects were blood eosinophil and cortisol levels, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia. RESULTS: The baseline FEV1 was comparable in the two groups: QD = 67% +/- 2% and QID = 66% +/- 2% of predicted value. After 4 weeks of treatment, FEV1 increased similarly in the QD group to 77% +/- 4% and in the QID group to 74% +/- 4% of predicted value. Likewise, the improvement in morning and evening peak expiratory flow rates was not significantly different between the groups. Both QD and QID groups experienced comparable daily decrements in beta-agonist use. The systemic responses to the two regimens as assessed by eosinophil count, morning serum cortisol, and 24-hour urinary cortisol were also comparable. CONCLUSIONS: The single daily administration of inhaled triamcinolone at 3:00 PM has no increased systemic effects and produces similar improvement in efficacy variables. A dosing strategy based on once daily dosing should increase compliance of inhaled steroid use in the clinical setting. PMID- 7797786 TI - The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. AB - BACKGROUND: The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort, previously reported from birth to age 4 years. METHODS: In this prospective, randomized, controlled study of food allergen avoidance in infancy, the prophylactic-treated group consisted of infants whose mothers avoided cow's milk, egg, and peanut during the last trimester of pregnancy and lactation and who, themselves, avoided cow's milk until age 1 year (casein hydrolysate supplementation before age 1), egg until age 2 years, and peanut and fish until age 3 years. The control group consisted of maternal/infant pairs who followed standard feeding practices. RESULTS: Despite a significant reduction in food allergy and milk sensitization before age 2 years, none of the following differed between the groups at age 7 years: food allergy, atopic dermatitis, allergic rhinitis, asthma, any atopic disease, lung function, food or aeroallergen sensitization, serum IgE level, or presence of nasal eosinophils or nasal basophilic cells. Children with food allergy by 4 years evidenced higher 7-year (current) prevalences of allergic rhinitis and asthma (p < 0.01). Atopic diseases/parameters at age 7 years were shown, by multivariate analysis (p < 0.05), to be associated with several genetic and environmental risk factors (male gender, maternal nonwhite ethnicity and asthma, and household smoking), as well as predictive atopic markers during infancy (elevated serum IgE level; egg, cow's milk, and peanut sensitization; and nasal eosinophils and nasal basophilic cells). CONCLUSIONS: These findings help to: (1) elucidate the natural history of atopic disease in high-risk children; (2) document the progression of allergy from atopic dermatitis, food allergy, and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy; (3) identify allergy predictive markers; and (4) expand our appreciation of the interactions of genetic and environmental factors in the development of atopy. PMID- 7797787 TI - Reproducibility of allergen-induced early and late asthmatic responses. AB - BACKGROUND: Constant-dose allergen inhalation challenges are frequently used to examine the effect of antiasthma drugs on the allergen-induced early and late asthmatic responses. The end-point measurements in such studies are the maximal early and late percent decreases in the forced expiratory volume in 1 second (FEV1). OBJECTIVE: Our purpose was to observe the reproducibility and to determine the sample sizes required for such studies. METHODS: Twenty-eight subjects with allergen-induced early and late responses were studied with two constant-dose allergen challenges separated by 2 to 12 weeks. The early response was measured as the maximum percent decrease in FEV1 during the first 2 hours and the late response as the maximum percent decrease in FEV1 between 3 to 7 hours. RESULTS: The mean +/- SEM early responses were 23.1% +/- 1.0% and 24.7% +/- 2.0%, whereas the mean late responses were 23.3% +/- 2.0% and 24.5% +/- 2.2%. Reproducibility of measurements were such that fewer than eight subjects are required, to show 50% attenuation of either the early or late response (with 90% power). CONCLUSIONS: The method of constant-dose allergen challenge is a sensitive tool for detecting changes in early and late asthmatic responses after the use of antiasthma medication. PMID- 7797788 TI - Serum reactivities to latex proteins (Hevea brasiliensis). AB - BACKGROUND: In recent years there has been an increasing incidence of allergy to latex among health care workers and children with spina bifida. The allergic response in these individuals can be severe and occasionally fatal. Several allergens have been identified with the use of sera from different patient groups. In our effort to identify reagents for in vitro testing and clinical use, we investigated the reactivities of latex proteins to sera collected from a wide range of patients with latex allergy. METHODS: Twenty-six serum samples were obtained from adult patients with latex allergy, both hospital workers and non hospital workers. Serum pools were made either from sera of children with spina bifida or sera of adult patients with latex allergy. Proteins from C-serum and latex particles of latex sap (nonammoniated) were separated by different gel electrophoresis techniques and evaluated for specific IgE binding by immunoblotting. RESULTS: More than 50% of the sera tested reacted to an 18 kd protein, a 25.6 kd acidic protein with an isoelectric point of 3.5, or to both proteins; whereas only 23% of the individual serum samples tested reacted to the rubber elongation factor, which has been reported to be a major latex allergen. The immunoreactive patterns of children's and adults' serum pools were similar but not identical. CONCLUSIONS: With the use of gel electrophoresis and immunoblotting techniques, different immunoreactive proteins were identified in C serum and particles of latex. Rubber elongation factor, which reacted to only 23% of sera tested, did not appear to cross-react immunologically with other latex allergens. PMID- 7797789 TI - Characterization of the isoforms of the group I allergen of Cynodon dactylon. AB - BACKGROUND: The group I allergen of Cynodon dactylon, Cyn d I, was found to consist of four to 10 isoforms. METHODS: We studied the isoforms with the use of two-dimensional gel electrophoresis. The antigenic difference of the isoforms was evaluated by radioimmunoprecipitation with monoclonal antibodies (MAbs). The acidic isoforms and the basic and neutral isoforms were further isolated by MAb affinity chromatography for RAST and competitive RAST. In addition, the N terminal sequence was evaluated by microsequencing. RESULTS: A total of 11 isoforms were found in Cyn d I in extracts prepared from different sources of Bermuda grass pollen (BGP). They were either acidic (Cyn d I-A, I-B, I-C, I-D, I E, I-F, I-G, I-H, and I-I), neutral (Cyn d I-X), or basic (Cyn d I-J). Cyn d I-G, with an isoelectric point of approximately 6.4, was constantly present in all the pollen preparations, whereas the content of the basic Cyn d I-J varied from less than 5% to greater than 20%. The molecular weight of the basic and neutral isoforms were slightly lower than those of the acidic isoforms. All isoforms shared a common antigenic determinant(s) recognizable by MAb 4-37, and the basic and neutral isoforms possessed a unique antigenic determinant(s) recognizable by MAb 1-61. RAST showed that both the acidic Cyn d I and the basic and neutral Cyn d I were recognized by human IgE in the pooled sera of persons allergic to BGP. Competitive RAST showed a high crossreactivity between the acidic and the basic and neutral isoforms. A 95% sequence identity also existed between the N-terminal 20 amino acid residues of basic Cyn d I-J and the dominant acidic isoform Cyn d I G. CONCLUSIONS: The present study disclosed that basic Cyn d I-J is an important allergen and that the content of this isoform varies in different lots of BGP. PMID- 7797790 TI - Relationship between oral challenges with previously uningested egg and egg specific IgE antibodies and skin prick tests in infants with food allergy. AB - BACKGROUND: Positive skin prick test (SPT) and RAST reactions to egg that had never previously been ingested have been observed in infants with food allergy. The likelihood of having clinical hypersensitivity reactions when egg is first ingested and the predictive value of SPT and RAST remain to be elucidated. OBJECTIVE: We investigated the relationship between egg-specific IgE antibodies and positive SPT reaction to egg, and the development of clinical hypersensitivity on the first exposure, in infants with food allergy. METHODS: The patient group consisted of 21 infants with food allergy and positive SPT and/or RAST reaction to egg, which they had never previously ingested; the control group of 12 infants had food allergy and negative test results. All subjects underwent double-blind placebo-controlled food challenges with egg. RESULTS: Thirteen of 21 patients (61%) and one of 12 control subjects (8%) had positive reactions to challenges (p < 0.01). Thirteen positive reactions to challenges (93%) elicited immediate symptoms. Late-onset eczema occurred in two children. SPT results showed a high sensitivity (0.92) and negative predictive accuracy (0.92), whereas specificity (0.57) and positive predictive accuracy (0.61) were poor. RAST did not have any diagnostic advantage over SPT. CONCLUSIONS: In infants with food allergy SPT with egg may be helpful in predicting which patients will react to the first exposure. PMID- 7797791 TI - IgE antibodies to recombinant forms of Fel d I: dichotomy between fluid-phase and solid-phase binding studies. AB - BACKGROUND: The major cat allergen Fel d I consists of two polypeptide chains linked by disulfide bonds, each of which has been expressed in bacteria. To investigate the antigenic structure of Fel d I, antibody binding to the native molecule and to each recombinant chain were compared. METHODS: Polyclonal human IgE and IgG antibodies and monoclonal antibodies (mAbs) to Fel d I were compared for binding to Fel d I, chain 1, or chain 2 by fluid-phase inhibition radioimmunoassay, RAST, and immunoabsorption. RESULTS: In the fluid-phase assay, neither recombinant chain significantly inhibited the binding of antibody to native Fel d I at concentrations of up to 10 micrograms/ml. Partial inhibition was observed when chain 1 was used, which inhibited the binding of two mAbs by 40% and 75%. In contrast, when the solid-phase RAST assay was used, IgE antibodies bound both chains with high specificity, and there was a good quantitative correlation between IgE antibody binding to Fel d I and both chain 1 (r = 0.58, p < 0.01) and chain 2 (r = 0.47, p < 0.01). Up to 70% of IgG or IgE anti-Fel d I antibodies could be absorbed by either chain 1 or chain 2, and both chains in combination produced similar absorption values in response to native Fel d I. Four mAbs were fully absorbed by chain 1, but not chain 2, and three mAbs were not absorbed by either chain. CONCLUSIONS: The results demonstrate a dichotomy between antibody binding to recombinant Fel d I chains, which may be explained by confirmational differences between the chains in the fluid phase or on solid supports. The results also suggest that chain 1 is an important site for mAb-defined B-cell epitopes on Fel d I. PMID- 7797792 TI - Potential role of interleukin-1 in allergen-induced late asthmatic reactions in guinea pigs: suppressive effect of interleukin-1 receptor antagonist on late asthmatic reaction. AB - Interleukin (IL)-1 is a pluripotential proinflammatory cytokine and is thought to be involved in the pathogenesis of bronchial asthma and late asthmatic reactions (LARs). To determine whether IL-1 plays a role in LAR, guinea pigs sensitized with Ascaris antigen were used. We evaluated IL-1 production by immunostaining with anti-IL-1 beta antibody and elucidated the action of IL-1 in LAR with recombinant IL-1 receptor antagonist. Immunostaining revealed that IL-1 beta-like immunoreactivity-positive cells increased in the airway walls and in bronchoalveolar lavage fluid after the antigen challenge. IL-1 receptor antagonist protein pretreatment reduced the generation of LAR in terms of pulmonary resistance. IL-1 receptor antagonist protein pretreatment did not change cellular components but reduced the percentage of hypodense eosinophils in bronchoalveolar lavage fluid. We also studied the direct effect of recombinant human IL-1 beta on pulmonary resistance and eosinophil activity measured as released eosinophil peroxidase activity. Recombinant human IL-1 beta did not change pulmonary resistance but primed eosinophils to release eosinophil peroxidase activity in response to platelet activating factor. Therefore these results suggest that IL-1 was produced in sensitized pulmonary tissue of guinea pigs by allergen exposure and played a role in the generation of LAR, at least partially by modulating the activation of eosinophils. PMID- 7797793 TI - IgE regulation by nematodes: the body fluid of Ascaris contains a B-cell mitogen. AB - Nematode infection of human beings or laboratory animals leads to markedly increased levels of circulating IgE, most of which is not specific to worm antigens. This phenomenon is known to be interleukin-4-dependent, but little is known about the mechanism of activation of the response. In an attempt to elucidate this mechanism, we have used a reductive approach with worm products rather than infections. In a previous article we showed that injection of the body fluid of the nematode Ascaris yields a marked increase in circulating IgE. In this study we demonstrate that the body fluid contains a B-cell mitogen. Incubation with purified splenic B cells with 50 micrograms/ml body fluid yields marked proliferation of B cells, as measured by tritiated thymidine uptake. Similarly, Ascaris body fluid stimulates G0 B cells to enter the cell cycle. T cells are unaffected by the mitogen, and the response is dependent on viable accessory cells. Contamination of Ascaris body fluid or reagents by bacterial lipopolysaccharide has been ruled out as a source of artefactual data. A model is proposed, which suggests that the B-cell mitogen in Ascaris body fluid stimulates polyclonal B-cell activity and that other nematode factors either stimulate the release of interleukin-4 or act in an interleukin-4-like manner to cause class switch to IgE. PMID- 7797794 TI - Homology of a bovine allergen and the oligomycin sensitivity-conferring protein of the mitochondrial adenosine triphosphate synthase complex. AB - We have characterized bovine allergens by constructing and analyzing a complementary DNA library from bovine skin. Clones producing proteins that reacted with IgE antibodies from persons with allergy were purified and sequenced. One set of the allergen-coding clones showed an almost complete homology with the bovine oligomycin sensitivity-conferring protein of the mitochondrial adenosine triphosphate synthase complex. The IgE antibodies adsorbed with the recombinant allergen reacted with an 11 kd protein in the cow dander extract. Binding of the IgE from patients allergic to the recombinant allergen expressed in Escherichia coli confirmed the allergen-coding ability of the complementary DNA sequence. The prevalence of the IgE-positive sera among patients with cow allergy and control subjects suggests that the recombinant allergen represents one of the minor allergens in cow dander. This is the first time a mammalian allergen has been identified as a protein with a known function. PMID- 7797796 TI - Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice. AB - BACKGROUND: The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. OBJECTIVE: This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. METHODS: Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. RESULTS: Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. CONCLUSION: This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation. PMID- 7797795 TI - Eosinophil-active cytokine from mononuclear cells cultured with L-tryptophan products: an unexpected consequence of endotoxin contamination. AB - BACKGROUND: The eosinophilia-myalgia syndrome, caused by a contaminant or contaminants in epidemiologically implicated L-tryptophan products, is characterized by eosinophilia and eosinophil degranulation. We hypothesized that immune cells are stimulated by implicated L-tryptophan and produce eosinophil active cytokines. OBJECTIVES: This study was designed to identify substances in L tryptophan causing the eosinophilia-myalgia syndrome. METHODS: Peripheral blood mononuclear cells were cultured with L-tryptophan products, and supernatants were tested for their ability to enhance eosinophil degranulation and survival in vitro and for their cytokine content. Subsequently, 46 different L-tryptophan lots were analyzed for their in vitro biologic activities. RESULTS: After peripheral blood mononuclear cells were cultured with implicated L-tryptophan, their supernatants enhanced eosinophil degranulation and survival. These activities were blocked by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody; immunoreactive GM-CSF was measurable in the supernatants. Monocytes, but not T lymphocytes, were the responding cells. However, no correlation was observed between the in vitro biologic activity and lots of epidemiologically implicated L-tryptophan products. This biologic activity in the L-tryptophan products was characterized as endotoxin. CONCLUSION: Although L tryptophan products stimulate peripheral blood mononuclear cells to produce GM CSF, this response is caused by endotoxin contamination of the L-tryptophan products and not by a specific L-tryptophan contaminant. Endotoxin contamination must be considered as a possible cause of eosinophil-active cytokine production by peripheral blood mononuclear cells. PMID- 7797797 TI - Occupational allergy caused by urticating hair of Brazilian spider. PMID- 7797799 TI - Dietitians' advice = positive change. PMID- 7797798 TI - Fatal asthma attack during an inhalation challenge with ultrasonically nebulized distilled water. PMID- 7797800 TI - What dietetics can learn from molecular biology. PMID- 7797801 TI - Barley as high-chromium food. PMID- 7797802 TI - State and federal efforts to trim health care costs embrace Medicaid waivers and managed care. PMID- 7797803 TI - Dietetics goes into therapy. PMID- 7797804 TI - Positive association between dietetics recommendations and achievement of enteral nutrition outcomes of care. AB - OBJECTIVE: To identify planned dietetics outcomes of care, dietitians activities performed an recommendations made, and outcome achievement and its relationship to recommendations followed. DESIGN: A multisite, single-group prospective pilot study was conducted to describe the care provided by dietitians to patients receiving enteral nutrition care. SUBJECTS/SETTING: Participants were 172 patients (16 of whom died during hospitalization) receiving at least 75% of nutrient requirements from enteral nutrition products. Subjects were from six acute-care facilities and one rehabilitation facility in the Chicago metropolitan area. MAIN OUTCOME MEASURES: Dietitians identified planned outcomes of care to be accomplished and documented activities performed during the provision of care. Data were collected to measure outcome achievement and to determine whether dietitians' recommendations were followed. STATISTICAL ANALYSES PERFORMED: Descriptive data are reported as frequencies or means +/- standard error. Odds ratios were constructed to estimate the association between dietitians' enteral care recommendations and the achievement of planned outcomes of care. RESULTS: Whether or not enteral nutrition outcomes of care were achieved was positively associated with dietitians' recommendations. The odds of patients' achieving the recommended energy intake goal (P < .001) or increasing (P < .01) or maintaining (P < .04) visceral protein stores were at least four times greater when dietitians' recommendations were followed than when they were not. In addition, dietetics activities performed at the local level were similar to established practices. APPLICATIONS: Dietitians can identify and measure outcomes of dietetics-related care that demonstrate positive contributions to the interdisciplinary enteral nutrition care process. PMID- 7797805 TI - Fat preferences and fat consumption of 3- to 5-year-old children are related to parental adiposity. AB - OBJECTIVE: To examine differences in preferences for high-fat foods, dietary fat intake, anthropometric measurements, and parental body mass index (BMI) among 3- to 5-year-old children. DESIGN: Children's fat intake was measured using 30-hour weighed food intake data from a standard menu. Children's fat preferences were assessed using a subset of foods from the standard menu. We obtained parents' BMI scores and children's anthropometric measurements including weight-for-stature, triceps, and subscapular skinfolds. SUBJECTS: Participants were children 3 to 5 years of age (n = 18, 10 girls and 8 boys; mean [+/- standard deviation] age = 52 +/- 1.9 months) who were without food allergies, food sensitivities, or chronic illness, and the children's parents (18 mothers and 16 fathers). STATISTICAL ANALYSES PERFORMED: Correlational analyses and maximum likelihood contingency tables were used to examine children's fat preferences and fat intake, children's anthropometric measurements, and BMI scores of parents. RESULTS: Although all children were offered the same daily menu, children's dietary fat intakes ranged from 25% to 42%. Children indicating strong preferences for high-fat foods had high total fat intakes (r = .54, P < .05; chi 2 = 3.96, df = 1, P < .05). Children's fat preferences were also related to their triceps skinfold measurements (r = .61; P < .01). Finally, those children with the strongest preferences for high-fat foods (r = .75, P < .01; chi 2 = 10.68, df = 1, P < .05) and the highest total fat intakes (r = .67, P < .01; chi 2 = 5.28, df = 1, P < .05) had heavier parents than did children with low scores. CONCLUSIONS: Offering children a nutritionally adequate diet is necessary but may not be sufficient to ensure dietary quality; children's food preferences are influential determinants of macronutrient intake. The association of children's fat preferences and intake with parental adiposity suggests that dietary influences may mediate familial patterns of adiposity. PMID- 7797806 TI - Evaluation of menus planned in Mississippi child-care centers participating in the Child and Adult Care Food Program. AB - OBJECTIVES: To collect information from licensed child-care centers in Mississippi on their foodservice operations relative to participation in the Child and Adult Care Food Program sponsored by the US Department of Agriculture (USDA); to collect information on who planned the menus; and to evaluate the energy and nutrient content of the planned menus relative to the suggested goal of one third of the Recommended Dietary Allowances (RDAs) and the recommendations made in the Dietary Guidelines for Americans. DESIGN: Survey questionnaire. SETTING: Licensed child-care centers in Mississippi. SAMPLES: Ninety-two licensed child-care centers provided cycle menus for analysis. One hundred eighteen centers returned the questionnaire. MAIN OUTCOME MEASURES: Content of the menus relative to the meal-pattern guidelines established for the Child and Adult Care Food Program; the energy and nutrient content of the menus relative to the RDAs and the Dietary Guidelines for Americans. STATISTICAL ANALYSES PERFORMED: One-way analysis of variance and frequencies. RESULTS: Seventy-five percent of the centers reported participating in the Child and Adult Care Food Program. All but one of the centers planned menus that met the meal-pattern requirements established by the program, licensure, and Head Start Performance Standards. Results showed that following the established meal-pattern guidelines for the child nutrition programs may not guarantee consistent nutritional quality of planned menus in child-care centers. The mean amounts of energy and many nutrients were significantly lower (P < .05) for centers that reported participating in the Child and Adult Care Food Program. Mean fat levels for all centers exceeded the recommendation of no more than 30% of total energy from fat: 40.8% of total energy from fat was reported by centers that participated in the program and 38% by those that said they did not. APPLICATIONS: Additional guidance is needed for menu planning in child-care centers to ensure compliance with the nutritional goal of meeting one third of the RDAs and Dietary Guidelines for Americans. PMID- 7797807 TI - Vegetables, fruits, and legumes: effect on urinary isoflavonoid phytoestrogen and lignan excretion. AB - OBJECTIVE: To compare the effect of vegetable, fruit, and legume consumption on urinary isoflavonoid phytoestrogen and lignan excretion. DESIGN: After 4 days of data collection, during which subjects consumed their habitual diets, subjects were randomly placed on four 9-day controlled experimental diets with each subject receiving each diet in a random order. SUBJECTS: Seven men and three women, aged 20 to 35 years, were recruited from the University of Minnesota Twin Cities community. INTERVENTIONS: All subjects consumed four experimental diets in an assigned random order: a controlled basal diet, a legume/allium diet (containing garbanzo beans, garlic, and onions), and diets low or high in vegetables and fruits (containing apples, pears, potatoes, and carrots). MAIN OUTCOME MEASURES: Urine samples that were collected while subjects consumed their habitual diets and during the last 3 days of each feeding period were analyzed for isoflavonoid and lignan content using isotope dilution gas chromatography mass spectrometry. STATISTICAL ANALYSIS PERFORMED: The effect of vegetable and fruit intake on urinary isoflavonoid and lignan excretion was analyzed using the general linear model procedure. Post hoc comparisons were made using Duncan's multiple range test. RESULTS: Subjects excreted more of the lignan enterodiol on the high vegetable/fruit diet compared with the basal and legume/allium diets (P = .03); more of the isoflavonoids O-desmethylangolensin (O-DMA), genistein, and sum of isoflavonoids on the legume/allium diet compared with the other controlled diets (P < .05); and more of the isoflavan equol on the basal and legume/allium diets compared with the high vegetable/fruit diet (P < .01). Subjects who excreted higher levels of equol on the basal and legume/allium diets also consumed more of the milk-based pudding provided as part of the controlled diets. CONCLUSIONS: Urinary lignan and isoflavonoid excretion changed in response to alterations in vegetable, fruit, and legume intake under controlled dietary conditions. PMID- 7797808 TI - Effect of antioxidant-rich foods on plasma ascorbic acid, cardiac enzyme, and lipid peroxide levels in patients hospitalized with acute myocardial infarction. AB - OBJECTIVE: To determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E, beta carotene, and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infarction. DESIGN: Randomized, single blind, controlled study. SETTING: Primary- and secondary-care research center for patients with myocardial infarction. SUBJECTS: All subjects with suspected acute myocardial infarction (n = 505) were considered for entry to the study. Subjects with definite or possible acute myocardial infarction and unstable angina (according to World Health Organization criteria) were assigned to either an intervention diet (n = 204) or a control diet (n = 202) within 48 hours of symptoms of infarction. INTERVENTIONS: Intervention and control groups were advised to consume a fat-reduced, oil-substituted diet. The intervention group was also advised to eat more fruits, vegetable soup, pulses, and crushed almonds and walnuts mixed with skim milk. MAIN OUTCOME MEASURES: Reduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels, increase in plasma ascorbic acid level, and compliance with diet, especially with vitamin C intake as determined by chemical analysis. STATISTICAL ANALYSIS: A two-sample t test using one-way analysis of variance for comparison of data. RESULTS: Plasma lipid peroxide level decreased significantly in the intervention group compared with the control group (0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group; 95% confidence interval of difference = 0.19 to 0.83). Lactate dehydrogenase level increased less in the intervention group than in the control group (427.7 vs 561.2 U/L; confidence interval of difference = 82.9 to 184.7). Plasma ascorbic acid level increased more in the intervention group than in the control group (23.38 vs 7.95 mumol/L; confidence interval of difference = 12.85 to 26.13). APPLICATIONS/CONCLUSIONS: Consumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid. Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals. PMID- 7797809 TI - Improving food frequency questionnaires: a qualitative approach using cognitive interviewing. AB - In an attempt to improve data quality and ease of administration of standard self administered food frequency questionnaires, various alternative approaches were tried for inquiring about frequency of consumption, portion size, seasonal intake, and food preparation. Evaluation consisted of a cognitive interviewing method in which respondents verbalize their thought process while completing several variations of a questionnaire. Interviewers observed and asked follow-up probe questions to evaluate problems or inconsistencies verbalized by respondents. Consensus and judgment by interviewers and observers suggested several problematic features of food frequency questionnaires: formatting of questions about frequency and portion size; computing average frequencies for aggregated food items or for foods eaten seasonally; comprehension of many items; and ordering of foods. These findings led to cognitive refinement and innovations, which included detailed questions regarding preparation or use of low-fat varieties or other alternatives to help better describe specifics of intake for some foods; questions on seasonal intake for several foods; inclusion of portion size ranges; and additional response categories for frequency of intake. Cognitive interviewing is an important step in pinpointing cognitive problems in dietary questionnaires. PMID- 7797810 TI - Potential renal acid load of foods and its influence on urine pH. AB - The purpose of this study was to calculate the potential renal acid load (PRAL) of selected, frequently consumed foods. A physiologically based calculation model was recently validated to yield an appropriate estimate of renal net acid excretion (NAE); the model depends primarily on nutrient intake data. When nutrient data from actual food composition tables were used, the calculation model yielded PRAL values that ranged from an average maximum of 23.6 mEq/100 g for certain hard cheeses over 0 mEq/100 g for fats and oils to an average minimum of approximately -3 mEq/100 g for fruits and fruit juices and vegetables. By means of these PRAL data (summed according to the amounts of foods and beverages consumed daily and by an estimate of excretion of organic acids [based on body size]), the daily NAE can be calculated. This calculation methodology, primarily based on PRAL, allows an appropriate prediction of the effects of diet on the acidity of urine. For practical applicability in dietetic prevention of recurrent urolithiasis or in other fields of dietetics, the additionally determined correlation (r = .83; P < .001) between NAE and urine pH can be used to ascertain NAE target values for a desired urine pH modification. PMID- 7797811 TI - Plasma and dietary vitamin C and E levels of tobacco chewers, smokers, and nonusers. PMID- 7797812 TI - Overweight in Cree schoolchildren and adolescents associated with diet, low physical activity, and high television viewing. PMID- 7797814 TI - Validity of a food frequency questionnaire for estimating calcium intake among Japanese and white women. PMID- 7797813 TI - Current caffeine intake of young children: amount and sources. PMID- 7797815 TI - Referrals to dietitians after cardiovascular screening program held in supermarket. PMID- 7797816 TI - Position of the American Dietetic Association: nutrition services for children with special health needs. PMID- 7797817 TI - Dietetics professionals' charge is to promote nutrition and physical activity. PMID- 7797818 TI - Food, physical activity, and fun: inspiring America's kids to more healthful lifestyles. PMID- 7797819 TI - Toxic effects of carbofuran and glyphosate on semen characteristics in rabbits. AB - The present study was undertaken to investigate the effect of chronic treatment with two sublethal doses of Carbofuran (carbamate insecticide) and Glyphosate (organophosphorus herbicide) on body weight and semen characteristics in mature male New Zealand white rabbits. Pesticide treatment resulted in a decline in body weight, libido, ejaculate volume, sperm concentration, semen initial fructose and semen osmolality. This was accompanied with increases in the abnormal and dead sperm and semen methylene blue reduction time. The hazardous effect of these pesticides on semen quality continued during the recovery period, and was dose dependent. These effects on sperm quality may be due to the direct cytotoxic effects of these pesticides on spermatogenesis and/or indirectly via hypothalami pituitary-testis axis which control the reproductive efficiency. PMID- 7797820 TI - Long-term mercury accumulation in the presence of cadmium and lead in Oreochromis aureus (Steindachner). AB - The effects of cadmium and lead on chronic mercury accumulation were investigated in O. aureus. After 140 days' exposure the accumulation of mercury in the liver, brain, gill filaments, intestine, caudal muscle, spleen, trunk kidney and eye was analysed. The exposure concentrations were 0.05, 0.10 and 0.20 mg/L for mercury alone. O. aureus was also exposed to mixtures of 0.05 mg/L mercury with lead (0.05 mg/L and 0.50 mg/L or cadmium (0.05 mg/L) and 0.10 mg/L mercury with 0.10 mg/L cadmium. In food fish, a knowledge of toxic metal accumulation patterns is of great importance because of their contribution to the human diet and, as fishmeal, to the diet of agricultural animals. The trunk kidney consistently accumulated higher concentrations of mercury than any of the other tissues investigated. PMID- 7797821 TI - Gallstones and upper abdominal discomfort. Innocent bystander or a cause of dyspepsia? AB - Many physicians consider gallstones to be a cause of vague upper abdominal discomfort. However, both dyspepsia and gallstones are common conditions in the general population, and the relationship between the two has continued to generate controversy. In this editorial, I review the evidence for and against a relationship between gallstones and dyspepsia. The data suggest that upper abdominal discomfort, heartburn, bloating, and other vague symptoms are not related to gallstones and the routine ordering of an ultrasound in the patient with dyspepsia is not warranted. PMID- 7797822 TI - Esophageal dilation can be done safely using selective fluoroscopy and single dilating sessions. AB - Maxims for safe esophageal dilation have included recommendations to use fluoroscopy in all instances and to limit dilation sessions to 2-mm increments. We reviewed a 34-month experience of all esophageal dilations undertaken at a large multispecialty clinic to define adherence to these recommendations and to delineate whether deviation was associated with significant complications. Four hundred thirty-two patients underwent 716 courses of esophageal dilation during this time, 92% of whom had benign disease. Eighty-nine percent of patients were dilated with polyvinyl dilators (Savary/American) and only 8% of these patients required fluoroscopic monitoring for the bougienage. Seventy-eight percent of the dilating sessions for patients without achalasia were undertaken using either a single large dilator (> or = 45 Fr) or employed incremental dilator sizes > 2 mm (6 Fr) in a single session. There was a single perforation in 662 nonachalasia dilations and this was a consequence of attempted placement of an esophageal endoprosthesis. We conclude that use of guide wire technology and newer dilating techniques do away with the need for routine fluoroscopic control. Moreover, single large dilators or dilator increments > 2 mm may be safely used, contingent on endoscopic stricture assessment. PMID- 7797823 TI - Endoscopic intrasphincteric injection of botulinum toxin for the treatment of achalasia. AB - Three patients with achalasia were treated with endoscopic injection of botulinum toxin (BoTx). BoTx (80 U) was injected via a sclerotherapy needle into the lower esophageal sphincter (LES). One patient complained of transient heartburn that resolved after omeprazole treatment. Two patients reported sustained symptomatic improvement. They were able to eat normally 48 h after treatment and have remained symptom free for 5 and 6.5 months, respectively. In these patients, esophageal manometry 4 months after treatment showed a marked reduction of resting LES pressure and the appearance of a previously absent LES relaxation after swallowing. The third patient had only a transient clinical improvement, with occasional dysphagia beginning 3 months after treatment. All patients showed unchanged aperistalsis of the esophageal body. Its less invasive nature compared with other therapeutic alternatives may give BoTX injection a role in the treatment of some patients with achalasia. PMID- 7797825 TI - Nonsteroidal antiinflammatory drugs are associated with gastric outlet obstruction. AB - Nonsteroidal antiinflammatory drug associated gastric ulcerations are often prepyloric and painless; when recurrent, such ulcers may lead to pyloric scarring and gastric outlet obstruction. We performed a retrospective case control study to seek an association between gastric outlet obstruction and nonsteroidal antiinflammatory drug use. The use of nonsteroidal antiinflammatory drugs in cases with gastric outlet obstruction was compared to an age- and sex-matched outpatient control group undergoing endoscopy. The proportion of drug use by patients with gastric outlet obstruction, seven of nine, was significantly higher than the proportion in controls, 29 of 90. The duration of nonsteroidal antiinflammatory drug use was also significantly longer in patients with gastric outlet obstruction than in control patients. Chronic nonsteroidal antiinflammatory drug use is associated with gastric outlet obstruction. PMID- 7797824 TI - Comparative trial of pantoprazole and ranitidine in the treatment of reflux esophagitis. Results of a German multicenter study. AB - In 249 patients with acute symptomatic reflux esophagitis grade II and III (Savary-Miller classification), we compared the efficacy and safety of pantoprazole, a newly developed proton pump inhibitor given at a once-daily dose of 40 mg, with a standard dose of the H2 receptor antagonist ranitidine (150 mg b.i.d.) in a randomized, double-blind, multicenter study. Complete healing was achieved after 4 and 8 weeks of therapy (protocol-correct) in 69 and 82% (pantoprazole) and 57 and 67% (ranitidine), respectively (p = 0.054 at 4 weeks and p < 0.01 at 8 weeks). The predominant symptoms of gastroesophageal reflux, i.e., heartburn and acid eructation, were more effectively reduced in pantoprazole- than in ranitidine-treated patients. The frequency of adverse events was low and did not differ between the two treatment groups. We conclude that pantoprazole is superior to ranitidine in the acute treatment of reflux esophagitis. PMID- 7797826 TI - Can the radiologist recognize Helicobacter pylori gastritis? AB - To evaluate radiologic findings of Helicobacter pylori (H. pylori) in the upper gastrointestinal (UGI) tract, we retrospectively reviewed consecutive records of 676 symptomatic adults with gastric biopsies (224 positive) and 150 symptomatic adults with rapid urease tests (57 positive). All the UGI series of patients with positive biopsies or urease tests for H. pylori were compared with the UGI series of patients with negative urease tests. UGI examinations were evaluated blindly by two gastrointestinal radiologists without knowledge of clinical findings, original radiologic interpretations, or test results. They agreed that 8 of 18 (44%) UGIs of patients with H. pylori had abnormally increased gastric folds in the fundus, body, or antrum as compared with none of 14 (0%) UGIs of patients without H. pylori (p < 0.01) (P.P.V. = 1.0). Interobserver agreement was good (kappa = 0.63). Endoscopy in the eight patients with radiographic evidence of enlarged gastric folds all demonstrated marked abnormalities such as prominent gastric folds, gastric erythema, erosions, or peptic ulcers. Our findings indicate that enlarged gastric folds on the UGI series of a symptomatic adult are very suggestive of H. pylori gastritis. PMID- 7797827 TI - A controlled double blind multicenter study of the effectiveness of 5 aminosalicylic acid in patients with Crohn's disease in remission. AB - We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohn's disease. Included were 59 patients who had proven Crohn's disease of at least 1 year's duration, and who had been in continuous remission for at least 6 months, while taking only 5 aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohn's disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohn's disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years. PMID- 7797828 TI - Intravenous cyclosporine for steroid-refractory attacks of Crohn's disease. Short and long-term results. AB - A prospective, open trial was conducted to test whether i.v. cyclosporine was effective in the treatment of refractory Crohn's disease. Eight patients with acute steroid-refractory attacks were included. Intravenous cyclosporine, 5 mg/kg/day, was added to ongoing drug therapy. Patients who responded were then switched to oral cyclosporine for a mean 2.6-month period, and steroids were discontinued when possible. Six patients improved, with a mean latency time to onset of improvement of 9 days. Two did not improve, and both underwent urgent operation. On oral cyclosporine, five patients maintained remission and discontinued steroids, whereas one relapsed and underwent surgery. After discontinuation of oral cyclosporine, the five remaining patients relapsed, and two underwent surgery. One reversible episode of hepatobiliary toxicity and one of gastrointestinal intolerance were recorded. We conclude that i.v. cyclosporine effectively and rapidly induces improvement of acute steroid-refractory flare-ups of Crohn's disease, but after discontinuation relapse is to be expected. PMID- 7797829 TI - Colonic transit in soccer players. AB - To evaluate the effects of exercise on colonic function, we measured total and segmental transit times in 11 male soccer players and nine male radiology student technicians. Diet was kept constant in all subjects, who maintained their normal activities. For the soccer players, normal activities included 15 h of training and one match each week. Transit times were measured with radioopaque markers, using the multiple-ingestion, single-radiograph technique. No overall difference in large bowel transit was observed between the two groups. Right colon transit was considerably slower in the soccer players, whereas left colon and rectal transit were slightly accelerated. We conclude that an intensive sport activity only modifies regional differences in large bowel function. This may be of importance in extreme conditions, such as those experienced by marathon runners. Data should be obtained before prescribing exercise to treat constipation. PMID- 7797830 TI - Serum lipid and fat-soluble vitamin levels in primary sclerosing cholangitis. AB - We reviewed the initial lipid and fat-soluble vitamin levels in 56 patients with primary sclerosing cholangitis (PSC) enrolled in a randomized, placebo-controlled trial evaluating ursodeoxycholic acid. We also evaluated lipid and vitamin levels in a group of 87 patients with advanced PSC being evaluated for liver transplantation. Of the patients entering the therapeutic trial, 41% had total serum cholesterol levels greater than the 95th percentile, whereas only 20% had high-density lipoprotein cholesterol levels above normal, and only one (2%) had an elevated triglyceride level. Total cholesterol levels were correlated with serum bilirubin levels and were lower in early versus later histologic stages (206 +/- 61 vs. 248 +/- 79, p = 0.04). Of the 87 pretransplant patients, 29% had elevated serum cholesterol levels and 17% had elevated serum triglyceride levels. Total serum cholesterol levels correlated inversely with total serum bilirubin levels in this group. In patients in the therapeutic trial, vitamin A deficiency was seen in 40%, vitamin D deficiency in 14%, and vitamin E deficiency in 2% of those tested. More prominent deficiencies of fat-soluble vitamins occurred in the pretransplant group of patients, with 82% deficient in vitamin A, 57% deficient in vitamin D, and 43% deficient in vitamin E. We conclude that hypercholesterolemia and fat-soluble vitamin deficiencies are frequent in patients with PSC and are more common with more severe disease. Patients with PSC, especially with advanced liver disease, should be screened for fat-soluble vitamin deficiencies and supplemented accordingly. PMID- 7797831 TI - The leading role of hepatitis B and C viruses as risk factors for the development of hepatocellular carcinoma. A case control study. AB - A double case control study evaluated the role of hepatitis C virus (HCV) and hepatitis B virus (HBV), alcohol drinking, and tobacco smoking as potential risk factors for cepatocellular carcinoma (HCC). Fifty-one patients with HCC, 34 of whom had underlying cirrhosis, were analyzed against 51 hospital controls and 34 patients with cirrhosis, respectively. Sera from patients of all three groups were tested for HBV markers and anti-HCV antibodies. The polymerase chain reaction technique was used to detect HCV RNA in the anti-HCV-positive samples. Alcohol drinking and smoking habits were recorded for all patients. HCC risk was significantly related to the presence of hepatitis B surface antigen (HBsAg) [relative risk (RR) = 18], HCV infection (RR = 8), and alcohol abuse (RR = 4). When the presence of cirrhosis was taken into account, only HBsAg positivity was significantly associated with HCC development (RR = 6.7), indicating that HCV infection and alcohol abuse are related to HCC indirectly through the cirrhotic process. No significant interaction between HCV and HBV infection in the causation of HCC was found. Through the computation of population-attributable risk, it was found that 46% of the HCC cases in Greece could be attributed to HBsAg positivity but only 4% to HCV infection. In conclusion, HBV infection is the major risk factor in the development of HCC in Greece, either by inducing cirrhosis or by direct oncogenic effect. HCV infection is also related to HCC development, albeit indirectly through the cirrhotic process. PMID- 7797832 TI - Protean manifestation of gastrointestinal tuberculosis: report on 130 patients. AB - Over the past 8 years, 820 patients with tuberculosis were seen at the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia. A total of 292 of these patients (35.6%) had pulmonary tuberculosis, and 130 patients (15.8%) had alimentary tract tuberculosis, making this the second commonest site of involvement. In these 130 patients, the disease was located in the upper gastrointestinal tract in 11 patients (8.5%), small bowel 44 patients (33.8%), large bowel 29 patients (22.3%), peritoneum 40 patients (30.7%), and liver 19 patients (14.6%). The diagnosis in most patients was made by specimens from endoscopy or laparoscopy, or liver or surgical specimens. Gastrointestinal tuberculosis is not uncommon in developing countries, and its incidence is increasing in developed countries due to immigration and in patients with AIDS or those receiving immunosuppressive therapy. It can mimic any diseases affecting the gastrointestinal tract and may present with very different symptoms, so a high index of suspicion is required. PMID- 7797833 TI - Metachronous small-bowel adenocarcinoma in celiac sprue. AB - Celiac sprue, or nontropical sprue, is associated with an increased incidence of digestive tract malignancy. We report a patient with celiac sprue who developed two primary adenocarcinomas of the jejunum > 2 years apart. The second cancer was asymptomatic and detected by surveillance computed tomography. Small-bowel cancers are unusual, and frequency of follow-up has not been established, so that it is important to have a high index of suspicion for these malignancies in celiac patients with vague gastrointestinal symptoms. PMID- 7797835 TI - Hepatorenal syndrome: resolution after transjugular intrahepatic portosystemic shunt. AB - Hepatorenal syndrome (HRS), a functional renal failure associated with severe liver disease, is believed to result from diminished effective arterial volume and altered renal hemodynamics. Death is almost inevitable after its development and therapeutic options are limited. Surgical shunts carry an increase in morbidity and mortality, and peritoneovenous shunts are frequently complicated by infection and coagulopathy. We report a case of hepatorenal syndrome successfully treated with transjugular intrahepatic portosystemic shunt (TIPS). This is an unusual therapeutic option for HRS and may lead to future indications for TIPS. PMID- 7797834 TI - Tuberculous pancreatitis: a diagnostic problem. Case report and review of literature. AB - A 22-year-old Pakistani man presented with a 1-year history of recurrent attacks of pancreatitis of unknown etiology that had required hospitalization and extensive investigation in Pakistan. He was admitted with abdominal pain, fever, and weight loss. An ultrasound and computed tomographic scan of the abdomen revealed abdominal lymphadenopathy, bulky and inhomogeneous pancreas, and a large fluid collection anterior to the right lobe of the liver. The collection was aspirated but Gram-stain, Ziehl-Neelsen stain for acid-fast bacilli, and DNA analysis by a highly specific polymerase chain reaction-based assay were negative. Because of a strong clinical suspicion of tuberculosis, the patient was started on antituberculous chemotherapy; 4 weeks later the aspirate grew Mycobacterium tuberculosis (hominis). The patient improved rapidly and has remained well after 18 months follow-up. A high index of clinical suspicion and appropriate microbiological investigation is required for the diagnosis of this rare, but potentially curable cause of pancreatitis. PMID- 7797836 TI - Hepatotoxicity and accelerated fibrosis following 3,4 methylenedioxymetamphetamine ("ecstasy") usage. AB - 3,4-Methylenedioxymetamphetamine ("ecstasy") has previously been reported to cause an acute hepatitis that may progress to liver failure. We present the first recorded case of ecstasy-induced accelerated hepatic fibrosis. PMID- 7797837 TI - Multiple angiomyolipoma of the liver. AB - Angiomyolipoma (AML) of the liver is extremely rare; we believe only about 60 cases, all solitary, have been reported. We present here the first reported case, to our knowledge, of multiple AMLs in the liver. Two masses were found in the liver of a 43-year-old Japanese woman complaining of abdominal discomfort by ultrasonography and computed tomography. With a preoperative diagnosis of hepatocellular carcinoma, a tumor in the right lobe 4.0 cm in largest diameter and one in the left lobe measuring 2.4 cm were resected. Histologically, both tumors were composed of smooth-muscle cells, fat cells, and blood vessels, and contained foci of extramedullary hematopoiesis. Although the smooth-muscle cell component was predominant and both tumors exhibited some pleomorphism, no mitosis was found. These histologic findings are consistent with the diagnosis of AML. PMID- 7797839 TI - Epstein-Barr virus-associated typical gastric carcinoma detected by in situ hybridization and polymerase chain reaction. PMID- 7797838 TI - Impaired gastric emptying following revision gastrostomy. PMID- 7797840 TI - Symptomatic peptic ulcer (PU): is there any seasonal variation? An endoscopic retrospective study. PMID- 7797842 TI - Primary malignant lymphoma of common bile duct presenting as acute obstructive jaundice: report of a case. PMID- 7797841 TI - 5-Aminosalicylic acid enemas to maintain remission in left-sided ulcerative colitis: a meta- and economic analysis. PMID- 7797843 TI - Recurrent acute pancreatitis and pancreatic pseudocyst as the presenting manifestation of HIV infection. PMID- 7797844 TI - Transverse myelitis heralding hepatitis A. PMID- 7797845 TI - Successful treatment of hepatitis B virus-associated polyarteritis nodosa by interferon alpha alone. PMID- 7797846 TI - Fatal hepatic failure due to prolonged amiodarone treatment. PMID- 7797847 TI - Severe hyponatremia and bradycardia associated with intravenous vasopressin therapy for variceal hemorrhage. PMID- 7797848 TI - Sjogren's syndrome with antimitochondrial antibody-negative primary biliary cirrhosis: a case of autoimmune cholangitis. PMID- 7797850 TI - Chronic wrist pain. PMID- 7797849 TI - Acute back pain in children. PMID- 7797852 TI - Assessment and treatment of common sites and causes of arthrosis in the wrist. PMID- 7797851 TI - Wrist arthroscopy. PMID- 7797853 TI - Arthroscopic assessment of carpal instabilities and ligament injuries. PMID- 7797854 TI - Endoscopic carpal tunnel release: Chow dual-portal technique. PMID- 7797855 TI - Endoscopic carpal tunnel release: single portal Agee technique. PMID- 7797857 TI - Current concepts in the treatment of fractures of the radial head, the olecranon, and the coronoid. PMID- 7797856 TI - Social and economic costs of carpal tunnel surgery. AB - In conclusion, we estimate the incidence of carpal tunnel surgery to be between 400,000 and 500,000 cases annually in the United States, with economic costs in excess of $2 billion per year. The costs incurred in workers' compensation cases are almost three times those of other workers and five times those of nonworkers. Despite an increase in medial costs for endoscopic carpal tunnel release, the procedure has a potential to decrease overall costs by lowering productivity and wage reimbursement losses. With better surveillance and data collection systems, workers at risk can be identified and the incidence of occupational carpal tunnel syndrome reduced through appropriate worksite intervention. PMID- 7797858 TI - Complex fractures of the distal part of the humerus and associated complications. PMID- 7797860 TI - Arthroscopy of the elbow. PMID- 7797859 TI - Fractures about the elbow. PMID- 7797863 TI - Primary arthroplasty of the hip in patients younger than 21 years of age. PMID- 7797861 TI - Fractures of the proximal part of the femur. AB - The orthopaedic surgeon has a multitude of internal fixation devices and techniques available for use in the treatment of subtrochanteric fractures of the proximal femur. The successful use of second-generation locking nails is technically demanding. Close attention to positioning of the patient, reduction of the fracture, placement of the guide-wire, and insertion of the nail and of the proximal and distal locking screws is mandatory. The newer, high-strength hip screws allow good fixation of a fracture that extends into the piriformis fossa. If medial comminution is present, this technique is best performed in conjunction with indirect reduction and bone-grafting. With proper technique, these devices allow the surgeon to manage predictably a complex subtrochanteric fracture that previously had to be treated with traction or extensive dissection and with (frequently inadequate) internal fixation. PMID- 7797862 TI - Fractures of the femur in children. PMID- 7797864 TI - Complex primary total hip arthroplasty: the difficult femur. PMID- 7797865 TI - Heterotopic ossification following total hip arthroplasty. AB - Although heterotopic ossification following total hip arthroplasty is frequently observed radiographically, it fortunately is much less commonly of clinical importance. There are, however, a group of patients that develop significant heterotopic bone formation, which can be symptomatic and, in some cases, can require repeat surgery. Careful surgical technique seems indicated in all patients undergoing total hip arthroplasty to try to reduce the incidence of this problem. Patients who are recognized to be at risk should be treated with prophylaxis. These include patients with active ankylosing spondylitis, skeletal hyperostosis, and prior heterotopic bone formation. Both low-dose radiation and nonsteroidal anti-inflammatories have been shown to be effective. The choice between these two modalities depends on the patient's individual circumstances, the availability of radiotherapy support (including custom shielding for ingrowth components), and the presence of areas of bone grafting and any osteotomies or fractures. Nonsteroidal anti-inflammatories, particularly Indomethacin, are a very acceptable form of prophylaxis and may be preferred in certain patients, including young women of childbearing age. Radiation is preferred in those patients with known GI intolerance to these medications or with a prior history of peptic ulcer disease. Excision of heterotopic bone, if symptomatic, should not be performed before 6 to 12 months and then only once it is clear that the process is mature. Bone scans can be helpful in assessing the maturity of heterotopic bone and can guide the timing of excision. Prophylaxis should be carried out in all patients following excision of heterotopic bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7797866 TI - Fractures of the femur after hip replacement. PMID- 7797867 TI - Metabolic bone disease. PMID- 7797868 TI - The role of antibiotic-loaded cement in the treatment of an infection after a hip replacement. PMID- 7797869 TI - Ankle fractures in children. PMID- 7797870 TI - Arthroscopic surgery of the ankle. PMID- 7797871 TI - Evaluation and emergent treatment of patients with thoracolumbar trauma. PMID- 7797872 TI - Reconstruction of the lateral ankle ligaments. PMID- 7797874 TI - Surgical management of fractures of the os calcis. PMID- 7797873 TI - Current methods for the evaluation of ankle ligament injuries. PMID- 7797876 TI - Women and their shoes: unrealistic expectations? AB - Is it unrealistic for a woman to consistently expect fashion and comfort in the same shoe? Probably so, unless, of course, the current fashion is shoes with a low heel, round toe, and cushioned sole. But, if the fashion trends of the last 300 years are any indication, it is doubtful that this will be the case any time soon. However, a woman who is willing to compromise with a properly fitting, low heeled, extra-depth or combination last pump augmented with a good quality cushioned insole has a better chance of finding comfort in a shoe. Although it is possible to have an orthopaedically sound shoe in a reasonably fashionable style, there is still room for the manufacturers and designers of shoes to improve the details of design. It is important to recognize that as long as society defines "fashionable" as a thin-soled, stiletto-heeled, narrow-pointed shoe, comfort and fashion are, to some extent, mutually exclusive. Any woman who wants the comfort of a tennis shoe will probably have to wear a tennis shoe. PMID- 7797875 TI - The high price of high-fashion footwear. PMID- 7797877 TI - Trends in women's shoewear. PMID- 7797878 TI - Anterior cruciate ligament reconstruction: why do failures occur? PMID- 7797879 TI - Revision ACL surgery: technique and results utilizing allografts. PMID- 7797880 TI - Revision ligament reconstruction of failed prosthetic anterior cruciate ligaments. PMID- 7797881 TI - The anatomic and surgical considerations for posterior cruciate ligament reconstruction. PMID- 7797882 TI - Posterolateral instability of the knee. PMID- 7797883 TI - Alignment in total knee replacement. PMID- 7797884 TI - Circular external fixation in high tibial osteotomy. PMID- 7797885 TI - Surgical management of thoracolumbar fractures. PMID- 7797887 TI - Pin and wire technique for external fixation. PMID- 7797886 TI - Management of the multiply injured patient with fractures. PMID- 7797888 TI - Walking, running, and sprinting: a three-dimensional analysis of kinematics and kinetics. AB - Just as in running, the two-joint muscles acting at the hip and at the knee work to transfer energy efficiently between body segments. This can be seen in Figure 12. The powers at the hip and knee are overlaid to show that when power is generated at the hip, it is absorbed at the knee and vice versa. For example, a concentric contraction of the hamstrings proximally at the hip is coupled with an eccentric contraction at the knee just prior to initial contact in terminal swing. The rectus femoris functions in a similar way but in an opposite direction in initial swing. For the three conditions discussed, the relative contribution of work occurring at each joint is different. Figure 13 shows that the muscles about the ankle are the most important source of work in walking and that the knee musculature does not significantly contribute to the work done for walking. In walking, the knee is felt to be important for the smoothing of gait. The quadriceps are a much more important source of energy at the knee in both running and sprinting, as can be seen in Figure 13. Finally, the hip musculature becomes the dominant source of work in sprinting in our group of untrained subjects with significant contributions from both the hip flexors and extensors. One would expect that the relative importance of each of the muscle groups about each of these joints in terms of sources of energy might change with training. The intent of this work was to evaluate the three conditions of walking, running, and sprinting. I hope that it will stimulate further interest and research in this area in order to come to a greater understanding of human locomotion. As more knowledge and experience are gained, the motion analysis lab will be able to offer insight into training strategies, injury prevention, and the treatment of pathologic running and sprinting conditions. PMID- 7797889 TI - The clinical use of kinetics for evaluation of pathologic gait in cerebral palsy. PMID- 7797890 TI - Computer applications for orthopaedic surgeons: CD-ROM and beyond. PMID- 7797891 TI - Computers for surgical planning of orthopaedic procedures. PMID- 7797892 TI - Database construction and use issues. PMID- 7797893 TI - Nonsurgical treatment of patients with thoracolumbar fractures. PMID- 7797894 TI - Treatment of acute injury of the cervical spine. PMID- 7797895 TI - Cervical spondylosis and myelopathy. PMID- 7797896 TI - Evaluation and management of cervical spondylotic myelopathy. PMID- 7797897 TI - Increased anti-influenza A virus cytotoxic T cell activity following vaccination of the chronically ill elderly with live attenuated or inactivated influenza virus vaccine. AB - The possible enhancement of anti-influenza A virus memory cytotoxic T cell (CTL) responses to inactivated influenza virus vaccine by coadministration of intranasal live attenuated influenza A virus vaccine was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. A larger proportion of volunteers who received live attenuated virus vaccine than of those who received placebo experienced a postvaccination rise in anti-influenza A virus CTL activity (15 of 23 vs. 8 of 24; P < .05). Anti-influenza A virus cytotoxicity was primarily mediated by CD8+ T cells and was influenza A virus-specific and HLA-restricted. There was a possible advantage of administering live attenuated with inactivated virus vaccine because of enhanced memory anti-influenza A virus CTL activity. PMID- 7797898 TI - Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome. AB - In 8 patients with symptomatic, acute primary infection with human immunodeficiency virus (HIV), a dramatic and persistent decrease in CD4+ lymphocytes was seen, accompanied by a marked increase in activated/memory CD8+ T cells (CD38+, CD45R0+, HLA-DR+, with high amounts of cell adhesion molecules), which represented most circulating lymphocytes, but no gross alterations in V beta T cell repertoire. Extremely high plasma levels of proinflammatory cytokines were observed. Three patients were followed for 2-3 years: The number of CD4+ cells, extremely low at first, increased significantly in a few months but decreased rapidly after a short stable period. Cytotoxic T lymphocytes bearing markers of immunologic activation/memory could play an important role in the earliest phases of the disease. It remains to be established how such a dramatic onset could determine the rapid progression of the infection that seems characteristic of patients with acute HIV syndrome. PMID- 7797899 TI - Use of human papillomavirus type 6 capsids to detect antibodies in people with genital warts. AB - Human papillomavirus (HPV) type 6 capsids were produced by recombinant vaccinia viruses and used in a capture ELISA to screen 901 human sera from three studies of genital HPVs. The highest seroprevalence was observed among subjects with recurrent genital warts. In a population-based case-control study of genital warts, 26 (58%) of 45 women with recurrent genital warts were seropositive compared with 19 (19%) of 101 control women with no history of genital warts (odds ratio, 6.5; 95% confidence interval, 3.0, 14.1). Among a cohort of pregnant women, 7 (88%) of 8 with recurrent warts were seropositive compared with 24 (30%) of 79 pregnant women with no such history. A significant association between seropositivity to HPV-6 capsids and the detection of HPV-6/11 DNA from genital specimens by polymerase chain reaction was also observed. Men with genital warts were less likely to be seropositive than were women with genital warts, and a positive association between the number of sex partners and seropositivity was observed among only the female university students. PMID- 7797900 TI - Protective effect of a 21-aminosteroid during experimental pneumococcal meningitis. AB - This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle of [corrected] U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-alpha, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis. PMID- 7797901 TI - The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus. AB - Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2. PMID- 7797902 TI - Epidemic streptococcal disease among Army trainees, July 1989 through June 1991. AB - Outbreaks of group A streptococcal infection occurred at four of seven US Army basic training installations between 1 July 1989 and 30 June 1991. Study data were collected through a respiratory disease surveillance program and on-site epidemiologic investigations. Although hospitalizations were frequent (range, 191 334) during each outbreak, average rates of hospitalization were low (2.4-4.8 hospitalizations/1000 trainees/week). Outbreak-associated morbidity included streptococcal toxic shock syndrome (2 cases, 1 fatal), acute rheumatic fever (6), acute glomerulonephritis (1), scarlet fever (1), and numerous other invasive sequelae. Four serotypes of Streptococcus pyogenes (M-1, -3, -5, and -18) were identified; M-18 caused significant disease at 2 installations. Disease control was rapidly achieved through prophylaxis programs using benzathine penicillin G in nonallergic trainees. These outbreaks extend other reports that document an evolution of the nature and severity of circulating S. pyogenes in the United States. PMID- 7797903 TI - Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life. AB - Two hundred children were followed from birth through 2 years of age with nasopharyngeal cultures to determine the normal colonization pattern of nontypeable Haemophilus influenzae. Forty-four percent of the children were colonized on one or more occasions; the acquisition rate was greatest in the first year. Monthly prevalence rates were 11%. Colonization with the initial strain persisted 1-5 months (median, 2). Children carried 1 predominant strain at a time but became colonized with up to 7 different strains (mean, 2.2). Children colonized with a single strain for < or = 2 months produced a greater nasopharyngeal secretory IgA to nontypeable H. influenzae response than did children colonized with different strains (log 2.35 +/- 0.68 vs. 1.89 +/- 0.25 U of P6 secretory IgA/ng/mL of total secretory IgA, P < .01). The duration of colonization with a strain and acquisition of a new strain may be affected in part by the local production of specific secretory IgA. PMID- 7797904 TI - Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. AB - To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1 antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans. PMID- 7797906 TI - Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis. AB - Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans. PMID- 7797905 TI - Synergistic effect of E5, imipenem, and volume support during fulminant intraabdominal sepsis in rats. AB - The protective effect of volume support, imipenem, and the anti-endotoxin antibody E5 given as mono- or combination therapy was studied in fulminant intraabdominal sepsis in rats. Mortality, blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed cell volume were measured. All monotherapy regimens improved survival, and protection decreased with delayed intervention. Volume support prevented dehydration and lactate accumulation but had no effect on levels of bacteria, endotoxin, or TNF. Imipenem killed bacteria and released endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF, and lactate but not bacteremia. The imipenem-induced increase in plasma endotoxin was abolished by E5. When E5 was added to a regimen of volume support plus imipenem 6 h after induction, it gave an extra improvement of survival, but this synergism disappeared when intervention was delayed 4 h more. The primary effect of E5 was a reduction in plasma endotoxin level. PMID- 7797907 TI - The emerging diversity of the electrophoretic types of Vibrio cholerae in the Western Hemisphere. AB - Since the Latin American cholera epidemic began in 1991, 447 isolates of Vibrio cholerae O1 from the Western Hemisphere have been assayed by multilocus enzyme electrophoresis (MEE) to determine allelic variation among 16 enzyme-encoding genes. Two electrophoretic types (ETs) were identified among toxigenic isolates from Latin America: 323 were ET 4, the ET associated with the Latin American epidemic, and 29 were ET 3. Twenty-three of these ET 3 isolates had a distinctive antimicrobial resistance pattern also seen in isolates imported into the United States from Latin America and Southeast Asia. These resistant isolates had an identical ribotype and nearly identical pulsed-field gel electrophoresis (PFGE) patterns. Most nontoxigenic isolates analyzed were not precursors or descendants of toxigenic epidemic strains. MEE provided a population genetic frame-work for the interpretation of PFGE and ribotype data from the isolates in this study. All three methods identified 2 distinct strains of toxigenic V. cholerae O1 currently epidemic in Latin America. PMID- 7797908 TI - Experimental human gonococcal urethritis: 250 Neisseria gonorrhoeae MS11mkC are infective. AB - Neisseria gonorrhoeae MS11mkA (mkA) expresses one 3.6-kDa lipooligosaccharide (LOS). Variant MS11mkC (mkC), expressing four larger LOSs, occurs in vitro among mkA at a frequency of 10(-3). Infectivity of these variants was compared in 2 groups of volunteers inoculated with approximately 40,000 piliated, Opa- gonococci of either strain. The mkC variant infected 5 of 5 while mkA infected only 2 (40%) of 5. Gonococci recovered from the mkA infections showed a transition toward the mkC LOS phenotype. The mkA inoculum contained approximately 40 mkC gonococci. These data confirmed earlier studies and suggested that small numbers of mkC gonococci would be infective. This hypothesis was tested in three more experiments. In two, volunteers were inoculated with 250 or 1250 mkC, infecting 3 of 7 in each group, and in the third, 1600 mkC infected 2 of 6, resulting in a total of 8 of 20 infected by < or = 1600 mkC. Gonococci shed by infected volunteers maintained the mkC LOS phenotype but shifted from Opa- to Opa+. Thus, LOS and opacity protein, as well as pilus, are gonococcal virulence factors. PMID- 7797909 TI - Inflammatory cytokines produced in response to experimental human gonorrhea. AB - Inflammatory cytokine production in men was examined after intraurethral challenge of volunteers with Neisseria gonorrhoeae MS11mkA or MS11mkC. Increased interleukin (IL)-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were detected in urine before the onset of symptoms and peaked simultaneously with the detection of IL-1 beta at the onset of symptoms. Urine cytokine levels returned to baseline or near baseline within 48 h after antibiotic therapy. In plasma, IL 8, TNF-alpha, IL-1 beta, and IL-6 were elevated at the onset of symptoms in 9, 5, 4, and 3 of 10 subjects, respectively, and returned to near normal within 48 h after treatment. IL-1 alpha and granulocyte-macrophage colony-stimulating factor were not consistently detected in urine or plasma after challenge. Cytokine mRNA transcripts in peripheral blood mononuclear cells were not altered by the infection. The findings suggest that IL-8, IL-6, and possibly TNF-alpha were produced at the local site of infection, whereas IL-1 beta was derived from infiltrating leukocytes. PMID- 7797911 TI - Differences in oxidant release by human polymorphonuclear leukocytes produced by stimulation with different phases of Coccidioides immitis. AB - Human polymorphonuclear leukocytes (PMNL) inhibit growth of arthroconidia and young spherules but not mature spherules of Coccidioides immitis. To evaluate these differences, oxidants were measured when PMNL were exposed to C. immitis or other particulate stimuli. Concentrations of arthroconidia, young spherules, mature spherules, and Candida glabrata were adjusted to result in equivalent superoxide release. Hydrogen peroxide and hypochlorous acid were stimulated by arthroconidia or young spherules but were undetectable after exposure to mature spherules. Levels of catalase in mature spherules were too low to account for the low levels of hydrogen peroxide and hypochlorous acid. When mature spherules were added to arthroconidia or zymosan, stimulation of hydrogen peroxide and hypochlorous acid occurred. The results suggest that mature spherules stimulate superoxide release but interfere with hydrogen peroxide and hypochlorous acid production. The low levels of these antimicrobial oxidants may contribute to resistance of C. immitis to human PMNL. PMID- 7797910 TI - Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. AB - A human papillomavirus (HPV) type 16 virus-like particle-based ELISA was used to assess antivirion immune responses in 300 women participating in cervical cancer case-control studies in Colombia and Spain. Virion IgG antibodies were detected in the sera of 51% and 59% of women with HPV-16 DNA-positive invasive cervical cancer and 81% and 73% of women with HPV-16 DNA-positive cervical intraepithelial neoplasia grade III (CIN III) in Colombia and Spain, respectively. Capsid antibodies were detected in 22% and 3% of cancer controls (P < .001) and in 43% and 10% of CIN III controls (P = .010) from Colombia and Spain, respectively. Since Colombia has an 8-fold higher incidence of cervical cancer, these results demonstrate an association between ELISA positivity and cancer risk. Capsid antibody responses did not correlate with humoral responses of the same women to HPV-16 E6 and E7 oncoproteins. PMID- 7797913 TI - Crude extract and recombinant protein of Cryptosporidium parvum oocysts induce proliferation of human peripheral blood mononuclear cells in vitro. AB - Cryptosporidium parvum preparations were studied for their ability to induce specific proliferation of cultured human peripheral blood mononuclear cells (PBMC) from both immunocompetent and human immunodeficiency virus-positive persons, some of whom had transient cryptosporidiosis. The proliferation of PBMC from sensitized donors induced by C. parvum preparations was due mainly to antigen-specific rather than nonspecific activation, as indicated by the kinetics of the proliferative response, inhibition of the PBMC proliferation by a monoclonal antibody directed against major histocompatibility complex class II specific HLA-DR molecule, and lack of proliferation of umbilical cord blood PBMC. PBMC from immunocompromised patients did not proliferate in response to C. parvum specific antigens. The supernatants of PBMC obtained from immunocompetent donors contained interleukin-10 and interferon (IFN)-gamma after PBMC were exposed to C. parvum preparations. High IFN-gamma values were found in patients who had recovered from cryptosporidiosis, suggesting that IFN-gamma plays a role in resolving this infection. PMID- 7797912 TI - Irreversible effects of ivermectin on adult parasites in onchocerciasis patients in the Onchocerciasis Control Programme in West Africa. AB - Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of approximately 30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazard. PMID- 7797914 TI - Safety and cellular and humoral immune responses of a booster dose of varicella vaccine 6 years after primary immunization. AB - Four hundred nineteen children and adolescents immunized with live varicella vaccine 4-6 years earlier were enrolled in a study to evaluate the safety and immune response to a booster dose containing approximately 3300 pfu of virus. Of the subjects, 99% (414/419) maintained antibody to varicella zoster virus (VZV) with a geometric mean titer of 25.7 and mean stimulation index (SI) for VZV specific lymphoproliferation response of 40.3 +/- 5.3 (SE). Some 7-10 days after the booster immunization, seropositivity rates increased to 100% (302/302), and GMT was 143.6 (anamnestic response). At 6 weeks after the booster inoculation, a subset of subjects had 100% seropositivity (74/74) with a GMT of 218.8 and an SI of 58.6. After 3 months, seropositivity was 100% (358/358), GMT was 119.0, and SI was 61.4. PMID- 7797915 TI - Establishment of novel lymphoid cell lines dually infected with human T cell lymphotropic viruses types I and II. AB - With the goal of establishing an in vitro system of dual infection with human T cell lymphotropic viruses (HTLV) types I and II, rabbit lymphocytes were cocultured with a mixture of lethally irradiated HTLV-I-producing Ra-1 and HTLV II-producing RII cell lines. This gave rise to a lymphoid cell line, RW-1, that was dually infected with HTLV-I and -II as detected by immunofluorescence staining, electron microscopy, and polymerase chain reaction using primers specific for the pol and env regions of each virus and by Southern blot hybridization. Two clonal cell lines derived from RW-1 were also coinfected with the viruses, indicating that dual infection had occurred at the single cell level. The coinfection could be readily propagated to fresh lymphocytes by coculture with RW-1. In contrast, attempts to superinfect HTLV-I-infected lymphoid cell lines with HTLV-II and vice versa were consistently unsuccessful, suggesting receptor interference between HTLV-I and -II. PMID- 7797916 TI - Foscarnet decreases human immunodeficiency virus RNA. AB - Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug. PMID- 7797918 TI - Transplantation of skin from human immunodeficiency virus type 1-transgenic mice to normal congenic mice results in graft rejection. AB - Skin from mice transgenic (Tg) for part of the human immunodeficiency virus type 1 (HIV-1) genome was transplanted onto normal mice of the same strain. All Tg grafts were rejected within 29 days. In contrast, skin from normal mice that was transplanted to HIV-1-Tg recipients remained viable for > 67 days. Histologic examination of Tg grafts on normal mice showed evidence of monocytic infiltrates. Monocytic infiltrates were not observed, however, when either normal or Tg skin was transplanted onto Tg mice. Immunohistologic staining verified the presence of gp120 protein expression in the Tg-transplanted skin but not in adjacent normal skin. It is concluded that the Tg mice are immunologically tolerant to the HIV-1 gene products they express. PMID- 7797917 TI - Human immunodeficiency virus (HIV) type 1 infection status and in vitro susceptibility to HIV infection among high-risk HIV-1-seronegative hemophiliacs. AB - Blood samples were obtained from 16 hemophiliacs who had a 50%-94% defined risk of human immunodeficiency virus (HIV) type 1 infection on the basis of treatment history and from 14 controls not at risk for HIV infection. HIV-1 was not detected in any of 12 patient samples by cocultivation nor in 14 patient samples by the polymerase chain reaction. Peripheral blood cells from 7 seronegative hemophiliacs at highest risk of seroconversion (94%) were less susceptible to HIV 1 infection in vitro than were cells from healthy controls (P < .025, one-tailed Wilcoxon rank sum test). In contrast, the susceptibility to HIV-1 infection of lymphocytes from 6 seronegative hemophiliacs at moderate risk (50%-56%) of seroconversion did not differ from that of cells from controls or from high-risk hemophiliacs. Therefore, prolonged periods of seronegative HIV-1 infection are not common in this high-risk population. In addition, among hemophiliacs there may exist heterogeneity in susceptibility to HIV-1 infection in vitro and in vivo. PMID- 7797919 TI - Incidence of venereal warts in human immunodeficiency virus-infected and uninfected women. AB - A cohort of human immunodeficiency virus (HIV)-infected (n = 253) and uninfected (n = 658) women was prospectively studied to assess the relationship between venereal warts and HIV status, adjusting for self-reported and biologic measures of sexual risk behavior. Participants were assessed every 6 months for venereal warts and other sexually transmitted diseases, self-reported sexual behavior, and CD4 cell counts. The incidence of venereal warts was significantly increased in HIV-infected women (8.2 vs. 0.8/100 person-years of follow-up). This difference remained after adjusting for measures of high-risk sexual behavior and was observed in women at all levels of immune function, including those with > or = 500/mm3 CD4 cells. The increased risk of venereal warts in HIV infection can occur relatively early in HIV disease and appears chiefly attributable to a higher risk of progression from subclinical to clinical human papillomavirus (HPV) disease rather than to a higher risk of HPV acquisition. PMID- 7797920 TI - Frequency of UL97 phosphotransferase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. AB - Cytomegalovirus (CMV) isolates from subjects who received ganciclovir therapy were tested for susceptibility to ganciclovir by a plaque reduction assay. Results were correlated with restriction enzyme and sequence analysis of the CMV UL97 phosphotransferase gene. Of the 30 isolates, 20 had one or more mutations in UL97 affecting amino acid encoding at codons 460, 520, or 591-596. All 20 were resistant to ganciclovir, with an IC50 of > 6.0 microM (range, 6.7-50.0). The remaining 10 isolates had no mutations at these loci; 8 were susceptible to ganciclovir while the other 2 were borderline resistant (IC50s, 6.6 and 7.2 microM). None of 40 control CMV isolates from untreated subjects contained any amino acid changes at these loci. The three most common mutations at codons 460, 594, and 595 were detected by restriction digest analysis in 16 (80%) of 20 isolates and in 16 (73%) of 22 isolates with ganciclovir IC50s > 6.0 microM. These results indicate that the majority of ganciclovir-resistant clinical isolates contain diagnostically useful mutations in UL97. PMID- 7797921 TI - Topical immunoglobulin is an effective therapy for parainfluenza type 3 in a cotton rat model. AB - A cotton rat model was used to test the efficacy of topical immunotherapy against parainfluenza type 3 (PIV3) infection. On day 3 after experimental infection with 10(5.5) pfu of PIV3, animals were treated with 2-fold dilutions of convalescent cotton rat serum or with one of two purified human immunoglobulin preparations; all three had moderate titers of anti-PIV3 neutralizing antibody (range, 1:200 1:1000). Therapy with high concentrations of all three preparations resulted in significant reductions of > or = 2 logs (> or = 100-fold) of pulmonary virus titers compared with titers for control animals. Little or no reduction in virus titers were seen in nasal tissues. PMID- 7797922 TI - Three summertime outbreaks of influenza type A. AB - In the Northern Hemisphere, sporadic cases of influenza occur during the summer, yet summertime outbreaks are rare. From 12 August through 2 September 1993, three influenza outbreaks in Louisiana were investigated using medical-record review, interviews, viral cultures, serology, and active surveillance for influenza-like illness in Louisiana. Attack rates in the outbreaks were 61% (69/114), 42% (24/57), and 45% (23/51). Viruses isolated were most closely related to influenza A/Beijing/32/92 (H3N2). The identification of influenza A as the cause of the first two outbreaks led to the recommendation for amantadine use in the third outbreak. Active surveillance did not detect any other outbreaks of influenza like illness during August or September 1993. Out-of-season influenza A outbreaks can therefore occur when little influenza-like illness is present in a community. Evaluation of outbreaks of acute, febrile respiratory illness outside the influenza season should include this possibility, since rapid detection can lead to the timely use of amantadine or rimantadine. PMID- 7797923 TI - Hepatitis C virus viremia in SCID-->BNX mouse chimera. AB - Chimpanzees are currently the only nonhuman animal model for reproducible propagation of hepatitis C virus (HCV). A chimeric mouse model was used for the induction of hepatitis C viremia, using BNX (beige/nude/X-linked immunodeficient) mice preconditioned by total body irradiation and reconstituted with SCID mouse bone marrow cells. HCV-infected liver fragments from patients with HCV RNA positive sera were transplanted under the kidney capsule of the chimeric mice. HCV-specific RNA sequences were detected by reverse transcriptase nested polymerase chain reaction (RT-PCR) in serum of approximately 50% of grafted animals. In addition, normal liver specimens were incubated with HCV serum and transplanted into chimeric mice, leading to viremia in approximately 25% of animals. Sequential histologic evaluation of the liver implants, from day 2 to week 14 after transplantation, revealed loss of lobular architecture within the implants. However, viremia persisted for 10-50 days after transplantation. These results offer a new HCV model. PMID- 7797925 TI - Comparison of trivalent cold-adapted recombinant (CR) influenza virus vaccine with monovalent CR vaccines in healthy unselected adults. AB - A trivalent cold-adapted recombinant (CR) influenza virus vaccine containing types A and B viruses was compared with monovalent vaccines of each virus in a double-blind, placebo-controlled trial. Adults with a wide range of preexisting antibody titers received one 0.5-mL dose intranasally of trivalent vaccine; monovalent A/H1N1, A/H3N2, or B vaccine; or placebo. All vaccines were well tolerated. Serum antibody response frequencies and postvaccination geometric mean antibody titers were similar for recipients of trivalent or the corresponding monovalent vaccine for each of the vaccine components. Stepwise logistic regression analysis of the antibody responses of trivalent vaccine recipients demonstrated that response to one vaccine virus did not adversely affect the likelihood of response to the other viruses. This study failed to find serologic evidence of interference between vaccine viruses, suggesting that trivalent CR influenza virus vaccine may be useful for preventing influenza in adult populations. PMID- 7797924 TI - Replication of influenza A viruses in a green monkey kidney continuous cell line (Vero). AB - A Vero cell line was investigated as a suitable host system for primary isolation and cultivation of influenza A viruses. The efficiency of primary isolation for currently circulating (H3N2) strains was similar in Vero and MDCK cells. Of 72 egg-adapted strains investigated, 90.3% were detectable hy hemagglutinin (HA) titration in Vero cells after the first passage and 51.4% after the second. The amino acid sequences of the HA1 region of influenza A viruses isolated and passaged in Vero cells were identical to those of their MDCK-grown counterparts. At low MOI, high yields of influenza virus were achieved in Vero cells by multiple additions of trypsin to the medium. After 20 passages of A/England/1/53 (H1N1) in Vero cells, the titer of infectious virus was 8.37 log10 TCID50/mL, and virus protein yields were as high as in MDCK cells. PMID- 7797927 TI - Quasispecies of hepatitis C virus and genetic drift of the hypervariable region in chronic type C hepatitis. AB - The sequential variations of amino acid sequences in the hypervariable region (HVR)-1 of hepatitis C virus (HCV) and changes of viremia in 2 patients with different clinicopathologic courses of chronic hepatitis C were studied. By using polymerase chain reaction amplification, cloning, and sequencing of HVR-1, genetic heterogeneity of HCV was shown. The highest annual rate of consensus amino acid variation per 100 sites in HVR-1 of a patient with acute exacerbation was 15.4 versus 2.3 in a patient without acute exacerbation. The serial serum HCV titers were also quantified. An abrupt elevation of serum titer was associated with acute exacerbation, whereas constant viremia was observed when acute exacerbation did not occur. These results show that a quasispecies of HCV exists and patients with different courses of chronic hepatitis may have different sequential changes in virus titer and genetic drift of HVR-1. PMID- 7797926 TI - A 3-week hepatitis B vaccination schedule provides rapid and persistent protective immunity: a multicenter, randomized trial comparing accelerated and classic vaccination schedules. AB - Hepatitis B (HB) vaccinations given once weekly for 3 weeks can provide early seroprotection. This study compared immune responses induced by the accelerated (A; days 0, 10, 21) and classic (C; days 0, 28, 56) HB vaccination schedules. Two hundred seventy healthy subjects (95 men, 175 women) with a mean age of 23.8 years received 3 doses of GenHevac B, a recombinant vaccine produced in mammalian cells. The subjects were randomly assigned to schedules A or C. A booster dose was given 1 year later. One month after the third dose, 70% (schedule A) and 92% (schedule C) of the subjects were seroprotected and 100% (A) and 99% (C) had developed anti-pre-S2 antibodies. Before booster injections, 93% (A) and 95% (C) of the subjects were seroprotected, and 1 month after the booster, almost all subjects were seroprotected. A 3-week HB vaccination schedule with GenHevac B can confer early protective immunity lasting up to 1 year. PMID- 7797928 TI - Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease. AB - An association of Chlamydia pneumoniae infection and reactive airway disease has been demonstrated in children. To determine if C. pneumoniae infection triggers production of C. pneumoniae-specific IgE, sera were examined from 45 children with and without C. pneumoniae infection. Anti-C. pneumoniae IgE was demonstrated by immunoblotting in 12 (85.7%) of 14 culture-positive asthmatic patients with wheezing compared with only 1 (9.1%) of 11 culture-positive patients with pneumonia, 2 (18.2%) of 11 culture-negative asthmatic children with wheezing, and 2 (22.2%) of 9 culture-negative asymptomatic patients. The most commonly recognized proteins were at 98 (82.4%), 78 (58.8%), 58-60 (70.6%), and 36 kDa (64.7%). The presence of anti-C. pneumoniae IgE by immunoblotting was not associated with the presence of anti-C. pneumoniae IgG and IgM by microimmunofluorescence. These results suggest that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection. PMID- 7797930 TI - Enterococcus faecalis cytolysin without effect on the intestinal growth of susceptible enterococci in mice. AB - A murine model was developed to determine whether the Enterococcus faecalis cytolysin, through its bacteriolytic action on gram-positive bacteria, could promote intestinal overgrowth of cytolytic strains. Sets of E. faecalis strains with varying cytolytic production and susceptibility to cytolytic activity were mixed 1:1 and allowed to compete in vitro in broth or in vivo after orogastric administration in mice pretreated with antibiotics. In general, cytolytic strains outgrew, by as much as 2000-fold, competing cytolysin-susceptible or hypersusceptible strains in vitro. In contrast, no growth advantage was observed in vivo, despite similar transient colonization of the murine intestinal tract by both cytolytic and cytolysin-susceptible strains. These data suggest that cytolysin plays little role in promoting intestinal overgrowth of enterococci through bacteriolytic activity. PMID- 7797929 TI - Extent and kinetics of genetic change in the omp1 gene of Chlamydia trachomatis in two villages with endemic trachoma. AB - Variants of Chlamydia trachomatis in two Gambian villages with hyperendemic trachoma were analyzed by omp1-based polymerase chain reaction and sequencing from conjunctival swabs. Samples collected over a 22-month period included a complete cross-sectional study of each village. Overall, 4 genovar A and 4 B variants were characterized by point mutations in the omp1 gene, resulting in changes in the inferred amino acid sequence. Two genovar A and 2 B variants accounted for 87% of the total ocular chlamydial infection in both villages. Although some flux in the prevalence of individual variants was observed overtime, their overall distribution remained remarkably stable. There was no evidence of major antigenic shift arising from recombination events at the omp1 locus as described for genital tract infection. These results indicate that omp1 variation in these two trachoma-hyperendemic communities is limited and unlikely to hamper development of trachoma vaccines based on the major outer membrane protein. PMID- 7797931 TI - Incidence of antibiotic resistance in Listeria species. AB - To define the prevalence of antibiotic resistance in Listeria species pathogenic for humans and animals, 1100 isolates (60 from cases of listeriosis and 1040 from food and environment) collected worldwide were screened. Of the 61 tetracycline- and minocycline-resistant strains (37 Listeria monocytogenes), 57 harbored tet(M); 4 non-L. monocytogenes isolates contained tet(S). One Listeria innocua isolate was also resistant to streptomycin and contained the tet(M) and aad6 genes. An L. monocytogenes isolate was trimethoprim-resistant, a characteristic not reported previously in Listeria species, because of the presence of a yet uncharacterized gene. Three clinical isolates of L. monocytogenes were resistant to low levels of streptomycin. Since the tet(M), tet(S), and aad6 genes are common in enterococci and streptococci, these data suggest transfer from the latter to Listeria species. Uniform susceptibility to tetracycline, minocycline, trimethoprim, and streptomycin cannot be assumed any longer for Listeria species. PMID- 7797932 TI - Comparison of polymerase chain reaction with microagglutination test and culture for diagnosis of leptospirosis. AB - Polymerase chain reaction assay (PCR) amplifying a fragment of the Leptospira rrs gene was compared with culture and microagglutination test (MAT) for the diagnosis of leptospirosis in a study of 200 patients with various clinical syndromes compatible with leptospirosis. For the first group of samples tested, PCR identified the 14 cases that later were unequivocally confirmed to be leptospirosis. Thirteen other systemic cases presenting decreasing leptospiral antibody titers were also detected by PCR. The average persistence of leptospiral DNA in serum was estimated at 12 days, with a maximum of 56 days in a culture confirmed case. The possibility of detecting leptospires in aqueous humor during the ocular complications of the disease was confirmed. The results suggest that PCR is an efficient tool for early diagnosis of leptospirosis during the first 10 days of the disease, especially when the clinical expression of the disease is confusing. PMID- 7797933 TI - Lyme disease in human DR4Dw4-transgenic mice. AB - The evolution of Lyme arthritis in DR4-transgenic mice infected with Borrelia burgdorferi was studied because chronic Lyme arthritis in humans is associated with an increased frequency of the HLA-DR4 allele. B10 nontransgenic and DR4 transgenic mice expressing chimeric human-mouse major histocompatibility complex class II genes in which the human alpha 1 and beta 1 domains of DR4Dw4 replaced the corresponding domains of the mouse I-E(d) were inoculated with B. burgdorferi and examined at up to 180 days for infection and disease. All mice were infected throughout the 180 days, and arthritis evolved to equal severity in transgenic and control mice within 30 days and resolved by day 120. Both groups of mice developed high antibody titers to B. burgdorferi, but antibodies to outer surface proteins A and B were not readily detectable. The DR4Dw4 transgene did not predispose mice to the development of chronic Lyme arthritis. PMID- 7797934 TI - Analysis of genetic diversity in cytotoxin-producing and non-cytotoxin-producing Helicobacter pylori strains. AB - Analysis of 32 Helicobacter pylori strains indicated a strong association between the presence of the cagA gene and a specific type of vacA allele found predominantly in cytotoxin-producing strains (P < .001). To determine whether tox+/CagA+ and tox-/CagA- strains constituted two separate noncombining lineages, sequences of the H. pylori ureC gene, cysS homologue, and the intergenic region between cysS and vacA were determined for multiple strains. The mean levels of nucleotide identity in the three regions were 96.7% +/- 0.5%, 95.0% +/- 1.0%, and 89.0% +/- 2.9%, respectively. Multiple sequence alignments and dendrograms based on these three regions failed to identify two clonal populations of organisms for which cagA and vacA genotypes were markers. The presence of a 63- to 64-bp insertion in the cysS-vacA intergenic region was unrelated to the vacA genotype of the strains. These data suggest that recombination between Helicobacter genomes may occur in vivo. PMID- 7797935 TI - Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. AB - Thirteen patients (median age, 20 years) with life-threatening primary septic shock (10 meningococcal, 3 pneumococcal infections) were studied prospectively. All had a short history of sepsis (< or = 24 h) and no severe underlying disease. Two (15%) died. The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively). The plasma levels of endotoxin, TNF-alpha, IL-1 beta, and PAI-1 decreased toward normal levels within the first 24 h of treatment, but IL-6 and IL-1ra levels remained high until clinical recovery. On admission, the molar excess of IL-1ra to IL-1 beta was > 2000-fold in 11 of the 13 patients. Acute plasmapheresis in 11 of the 13 patients significantly increased the plasma clearance of TNF-alpha (P = .02). PMID- 7797936 TI - Assessment of a possible imbalance between tumor necrosis factor (TNF) and soluble TNF receptor forms in tuberculous infection of the central nervous system. AB - Distributions of tumor necrosis factor (TNF) and its soluble receptor forms, R55 BP and R75-BP, were analyzed in the cerebrospinal fluid of patients with severe acute or chronic central nervous system infections. Tuberculous infections were associated with high ratios of R55-BP and R75-BP to TNF, 27.2 and 28.0, respectively, suggesting a small biologically active fraction of TNF. The opposite was found in subjects with acute bacterial meningitis. They had large fractions of biologically active TNF and thus low ratios of R55-BP and R75-BP to TNF, 3.7 and 4.0, respectively. It is hypothesized that chronic infectious diseases, such as tuberculous infections, may be associated with inadequate production of TNF and a concomitant relative increase of soluble TNF receptors, which may prolong the disease. PMID- 7797937 TI - Phospholipase A2 is a circulating mediator in typhoid fever. AB - Circulating proinflammatory mediators have not been found in studies on typhoid fever, although the patients suffer from a systemic disease with characteristic protracted fever. The 14-kDa group II extracellular phospholipase A2 (PLA2) is induced by interleukin-1 and tumor necrosis factor and may mediate some of the effects of these cytokines. Circulating PLA2 concentrations were measured in 12 typhoid fever patients on various days after admission and after recovery. On admission, mean concentrations of PLA2 were elevated (1444 +/- 1560 ng/mL) and decreased gradually and significantly to day 14 (55 +/- 48 ng/mL). patients with complicated disease had significantly higher PLA2 levels on admission. PLA2 was not produced in a lipopolysaccharide-stimulated whole blood culture, indicating that PLA2 originates from other types of cells. These data indicate that PLA2 may be a mediator of disease in protracted inflammatory diseases such as thyroid fever. PMID- 7797938 TI - Coagulation of whole blood stimulates interleukin-1 beta gene expression. AB - To study interleukin (IL)-1 beta gene expression, reverse transcription polymerase chain reaction was used on 25-microL whole blood samples from 11 healthy subjects. Coagulated and unclotted whole blood was compared. There was no evidence of IL-1 beta gene expression in any time zero samples (i.e., whole blood from which mRNA was immediately extracted) from 11 subjects, whereas a 388-bp band representing IL-1 beta mRNA was detected in all coagulated samples. No mRNA for IL-1 beta was detected in EDTA-anticoagulated whole blood, although in these samples the addition of lipopolysaccharide as a positive control induced the expression of IL-1 beta. In time course studies on samples allowed to clot, mRNA for IL-1 beta was detectable after 30 min. These findings demonstrate that IL-1 beta gene expression is not present in circulating cells of healthy subjects and that coagulation is a stimulus for IL-1 beta gene expression. This may be a mechanism by which thrombosis produces inflammation and fever. PMID- 7797939 TI - Experimental hepatitis E in pregnant rhesus monkeys: failure to transmit hepatitis E virus (HEV) to offspring and evidence of naturally acquired antibodies to HEV. AB - In an attempt to reproduce experimentally the fulminant hepatitis of pregnant women infected with hepatitis E virus (HEV), 4 nonpregnant and 6 pregnant rhesus monkeys in the first, second, or third trimester of pregnancy were inoculated intravenously with approximately 10(5.5) ID50 of HEV. Comparison of biochemical, histopathologic, and serologic profiles in pregnant and nonpregnant monkeys did not reveal an increase in the severity of hepatitis in the pregnant animals. Hematology and serum clinical chemistry values were in the normal range in all animals during the study. No evidence of neonatal infection with HEV was found in offspring. Two rhesus monkeys (1 pregnant, 1 nonpregnant) had naturally occurring anti-HEV antibodies prior to inoculation as detected by a standard ELISA and confirmed by a competition ELISA with hyperimmune chimpanzee serum. These animals demonstrated an anamnestic response when they were challenged with HEV. PMID- 7797941 TI - Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children. AB - The role of genetic factors in determining the clinical response of children to Plasmodium falciparum infection is not fully understood. A longitudinal survey of malaria morbidity in a cohort of 258 pairs of twin children was conducted in a rural area of Gambia to assess the extent to which genetic factors determine the host's susceptibility and clinical response to infection. The marginal correlation (which measures the excess probability of both twins being affected above that expected assuming independence) for malaria was higher in dizygous (DZ) than in monozygous (MZ) twin pairs, indicating that infection per se is largely determined by environmental factors. Once infected however, both members of an MZ pair were more likely to develop fever than were twins of a DZ pair, suggesting that genetic factors influence the presentation of clinical disease. PMID- 7797940 TI - Empirically treated Pneumocystis carinii pneumonia in Los Angeles, Chicago, and Miami: 1987-1990. AB - Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases, persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP. PMID- 7797942 TI - Potential of the polymerase chain reaction in the diagnosis of active Toxoplasma infection by detection of parasite in blood. AB - Blood samples from 54 patients presenting with acute toxoplasmic lymphadenopathy were tested for the presence of Toxoplasma gondii DNA using a nested polymerase chain reaction (PCR). PCR test results of a single blood sample obtained 2-23 weeks after onset of illness were positive for 19 (35%) of the 54 patients. Nine (53%) of 17 patients were positive by PCR when the initial blood sample was collected within the first 5 weeks of illness. In 7 of the 19 patients found positive, further blood samples were available, and subsequent clearance of T. gondii DNA from the blood was demonstrated. On the basis of positive findings among patients with acute toxoplasmosis and the absence of positive findings among 10 uninfected persons and 43 with past Toxoplasma infection, a positive PCR result appears to be a helpful indicator of active disease. However, since only 53% of patients with lymphadenopathy persisting < or = 5 weeks were positive, a negative PCR result does not exclude recent infection. PMID- 7797943 TI - Leishmania-human immunodeficiency virus coinfection in the Mediterranean basin: isoenzymatic characterization of 100 isolates of the Leishmania infantum complex. AB - Isoenzymatic characterization was done on 100 isolates obtained from visceral leishmaniasis (VL) patients coinfected with human immunodeficiency virus (HIV); isolates had been received between 1986 and 1993 at the International Leishmania Cryobank and Identification Centre in Montpellier, France. Electrophoresis was done with 15 isoenzymes using the starch gel technique combined, where appropriate, with isoelectrofocusing. Nine Leishmania infantum zymodemes were identified; L. infantum zymodeme MON-1, the most common parasite of human VL in the Mediterranean basin, was the most frequent in coinfections. It could also occasionally be responsible for localized cutaneous leishmaniasis lesions. Several dermotropic zymodemes, which were responsible for localized cutaneous leishmaniasis in immunocompetent patients, caused VL in HIV-positive patients. In addition, in 10 patients, a second isolate obtained during relapses occurring between 1.5 and 9.0 months after treatment was identical to the original isolate. PMID- 7797945 TI - First detection of group C rotavirus in fecal specimens of children with diarrhea in the United States. AB - Group C rotaviruses cause sporadic cases and outbreaks of acute diarrhea in children and adults in many countries but have never been identified from patients in the United States. Fecal specimens from children with diarrhea who were hospitalized in Providence, Rhode Island, were screened for group C rotaviruses if rotavirus was detected by electron microscopy but the specimens were negative for group A rotavirus by ELISA. Of 16 specimens examined, 3 were positive for group C rotavirus by ELISA using reagents specific to the Cowden strain of porcine group C rotavirus and all 16 were positive using a more sensitive assay: reverse transcriptase-polymerase chain reaction. Group C rotavirus infections occurred primarily among infants in winter in 4 of the 5 years examined and were acquired both in community and nosocomial settings. Future clinical and epidemiologic studies with group C rotavirus will require development of assays that are more sensitive and simpler to perform. PMID- 7797944 TI - A macaque model for hantavirus infection. AB - Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hallnas), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and microhematuria. Histopathologic changes during the first 7 weeks after infection were largely confined to abnormalities in medullary tubular cells of the kidneys, which coincided with the demonstration of viral antigen and viral RNA. The development of different classes of virus-specific plasma antibodies to the respective viral antigens were similar to those observed in humans with nephropathia epidemica. This first description of a nonhuman primate model for hantavirus infection shows that the cynomolgus macaque provides a suitable model with which to study the pathogenesis of Puumala virus infections and to evaluate new diagnostic methods, immunization strategies, and therapies. PMID- 7797946 TI - Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users. AB - Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV II, and HTLV-II infection is associated with HIV-1 and sociodemographic background. PMID- 7797947 TI - Zidovudine treatment prolongs survival and decreases virus load in the central nervous system of rhesus macaques infected perinatally with simian immunodeficiency virus. AB - To assess the potential therapeutic effects of zidovudine, rhesus macaques were inoculated with simian immunodeficiency virus (SIV) strain SMM/B670 at birth and infused either continuously or intermittently with zidovudine for 6-7 months. Zidovudine did not prevent infection but did significantly increase survival time, which was associated with lower serum p26 viral core antigen levels, a lower virus burden in the cerebrospinal fluid (CSF), and lower CSF quinolinic acid levels than in untreated monkeys. Two of 5 infected, untreated monkeys developed motor impairment within 6 months following infection, whereas motor impairments did not occur in infected, zidovudine-treated monkeys until after the drug was discontinued. Zidovudine treatment was well tolerated by rhesus infants with minimal, transient side effects. These results demonstrate that zidovudine treatment significantly decreases virus load within the central nervous system (CNS) and delays the onset of CNS dysfunction and immune disease in rhesus monkeys perinatally infected with SIV. PMID- 7797950 TI - [69th annual meeting of the Japanese Association for Infectious Diseases. Fukuoka City, Japan. April 13-14, 1995. Abstracts]. PMID- 7797948 TI - In vitro T cell function, delayed-type hypersensitivity skin testing, and CD4+ T cell subset phenotyping independently predict survival time in patients infected with human immunodeficiency virus. AB - Human immunodeficiency virus type 1 (HIV-1)-infected patients (n = 335) in the US Air Force HIV Natural History Program were followed for 3 years (mean) after skin testing, immunophenotyping of CD4+ cell subsets, and measurement of in vitro interleukin-2 production after stimulation by phytohemagglutinin, alloantigens, tetanus toxoid, and influenza A virus. The T cell functional assay predicted survival time (P < .001) and time for progression to AIDS (P = .014). Skin testing for tetanus, mumps, and Candida antigen and the total number of positive tests (P < .001 for each) stratified patients for survival time. In a multivariable proportional hazards model, the T cell functional assay (P = .008), the absolute number of CD4+ T cells (P = .001), the percentage of CD4+ CD29+ cells (P = .06), and the number of reactive skin tests (P < .001) predicted survival time. Thus, cellular immune functional tests have significant predictive value for survival time in HIV-1-infected patients independent of CD4+ cell count. PMID- 7797951 TI - [Analysis of the drill hole orientation in anterior cruciate ligament reconstruction]. AB - In the reconstructive procedure of the anterior cruciate ligament (ACL), the relationship was investigated between the orientation of the drill holes from the isometric points and the deformity in the ligament graft. We first investigated, by numerical analysis, the optimal orientation of the drill holes for minimal deformation. Secondly, we experimentally by using eight fresh cadaveric knees, measured the relationship between the orientation of the drill holes and the bending angle in the grafts. The optimal orientation of the drill hole in the femur was found to be tilted 20 degrees laterally in the coronal plane and 23 degrees anteriorly in the sagittal plane. In the tibia, the drill hole should be directed 24 degrees medially and 50 degrees anteriorly from the isometric point. The numerically analysed bending angle corresponded well to the results from the experimental study. The deformation in the graft on the femoral side was larger than that on the tibial side. Therefore, the orientation of the femoral drill hole was concluded to be more important than the orientation of the tibial drill hole. PMID- 7797949 TI - The predictive value of T cell function in vitro and pre-AIDS zidovudine use for survival after AIDS diagnosis in a cohort of homosexual men in Amsterdam. AB - The best independent predictors of survival after AIDS diagnosis were determined in 160 homosexual men from the Amsterdam Cohort Study (1987 CDC case definition). In a Cox model, all pre-AIDS laboratory markers gathered during follow-up in the study did not independently predict survival after AIDS. A second analysis, using data available only at AIDS diagnosis, revealed that T cell reactivity after stimulation with phytohemagglutinin and monoclonal CD3 antibodies and the CD4+ cell count at diagnosis were independent predictors of survival. In an interval based Cox model, the predictive value of pre-AIDS zidovudine use was determined. One year after AIDS diagnosis, participants with pre-AIDS zidovudine use had a worse survival probability (relative hazard = 3.99). In conclusion, the survival probability of homosexual men with AIDS can be estimate adequately using information obtained at clinical AIDS diagnosis. Analysis revealed the important predictive value of T cell function tests in vitro. PMID- 7797953 TI - Antitumor effects of liposomes containing adriamycin on chemically-induced rat malignant fibrous histiocytoma. AB - Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma. No effective chemotherapeutic agents, however, have been reported. Here we report our evaluation of the antitumor effects of liposomes containing adriamycin (LADM) against chemically-induced rat MFH. Either free adriamycin (ADM) or LADM was administered at dosages of 4.0, 8.0 or 12.0 mg/kg by intravenous injection. The tumor responded to LADM with prolonged growth delay, but equivalent doses of free ADM were less effective. Additionally, LADM prolonged the life span of rats longer than did free ADM. Also, the body weight loss was less with LADM than with equivalent doses of free ADM. In tissue distribution studies, we observed that the ADM level in the blood and in the tumor with LADM remained higher than with free ADM. These results indicate that liposomes alter in vivo ADM tissue distribution and increase antitumor activity against rat MFH with reduced toxic side effects. PMID- 7797952 TI - [An experimental study on preserving the intervertebral discs, in dog--prior to disc allografting]. AB - Disc grafting is a new surgical procedure that may be suitable for preserving mobility of the spine. This experimental study was designed to determine a method of favorably preserving a disc prior to allografting. The lumber vertebrae of adult mongrel dogs were aseptically excised, regarded as the vertebral body-disc unit, and preserved at -80 degrees C, or at 4 degrees C. In the preservation at 4 degrees C, UW solution, Euro-Collins solution, EP-II solution, Ham's F-12, or physiological saline solution was used for preservation. Isotopes were used for determining the activities of the disc cells. In the preservation at -80 degrees C, it was difficult to maintain the activity regardless of the preservation period. There was no difference among these preservative solutions in the preservation at 4 degrees C on the nucleus pulposus, but the 2-day preservation in UW solution provided the best results in terms of the annulus fibrosus. Based on the results of these experiments, at -80 degrees C it was difficult to maintain the activity of disc cells while at 4 degrees C the UW solution was the most effective for preserving the anulus fibrosus. However the period of preservation was very short, and a new method to enable longer periods of preservation should be developed. PMID- 7797954 TI - Canine cadaveric study of flexor tendon repair using tendon splint: tensile strength and the work of flexion. AB - A total of 128 flexor tendon repairs in zone II were performed with various suture techniques using a canine cadaver model to determine the tensile strength, gap strength, and resistance to tendon gliding as measured by the work of flexion. The ultimate tensile strength in kilogram force (kgf) following tendon laceration and repair was the greatest after repair by the Savage technique (4.84 kgf) and the dorsal tendon splint technique (4.89 kgf), while the standard Kessler technique showed a strength of only 1.48 kgf. The greatest gap strength values were also obtained for the Savage and dorsal tendon splint techniques. The work of flexion increase was the greatest at 85.5% after repair using a mesh sleeve technique. While, the Savage and dorsal tendon splint techniques showed an increase of 24.3% and 25.1% with no significant difference compared to the other technique studied. Considering the values of these biomechanical parameters, we believe that the best flexor tendon repair techniques in the canine model are the Savage and dorsal tendon splint. PMID- 7797955 TI - [Pathogenesis of acute and chronic compression neuropathy]. AB - The purpose of this study was to clarify the morphological changes in the cell body following acute, and chronic, nerve compression injuries. One hundred and fifty-eight adult male Wistar rats were used for the experiments. Acute compression was produced by clamping the sciatic nerve (ca. 1.3 mm diameter) using a stainless steel Micro-Tube-Clamp (1.6 mm-width and an internal diameter of 1.0 mm). To produce chronic entrapment neuropathy, we used Mackinnon-Dellon's procedure, in which a 1.0 cm length of Silastic tube with an internal diameter of 1.51 mm was wrapped around the nerve trunk. The morphological and functional changes in the nerve trunks were then studied. Histological examinations and morphometric measurements of the nerve cell bodies in the L5 dorsal root ganglion were also carried out for up to 15 months after the procedure. Degeneration of large myelinated nerve fibers, interfascicular edema, interruption of the blood nerve barrier and a delay in the fast orthodromic axonal transport were found as early as 1 day after clamping, a decreased in the motor nerve conduction velocity on the third day, and a thickening in the perineurium after 1 week. In the chronic experiment, these changes were found at 4, 4, 2, 8, 8, and at 2 months after wrapping, respectively. A significant change in the nuclear eccentricity was morphometrically discovered in both types of nerve compressions-on the third day after clamping, and at 6 months after wrapping. In addition, dispersion of Nissl substance, dislocation of cell organelles and an increase in the number of cytoskeletons were observed in the somata. Acute and chronic nerve compression induced morphologic changes in the nerve cell body as well as in the peripheral nerve fibers. These findings suggested that compression of the peripheral nerve fiber changed the metabolic activity of the nerve cell body. We concluded that compression neuropathy affected the whole neuron including the nerve cell body. PMID- 7797956 TI - [Pathology and treatment of temporomandibular joint disorders--intra-articular injection therapy and arthroscopic surgery]. PMID- 7797958 TI - Metacarpophalangeal joint prostheses. A review of the clinical results of past and current designs. AB - The clinical results of past and current hinge, flexible and third generation designs of MP prosthetic joints are reviewed. The hinged prostheses did not achieve acceptable short term clinical results while the silastic and third generation prostheses provided good results with with correction of deformity and adequate range of motion (ROM). These good short term results did, however, get progressively worse with the recurrence of deformities and loss of ROM. It is evident that while most of the existing prostheses can relieve pain and restore appearance, none provide the degree of stability and ROM that is required to restore normal function to the MP joint. The moderate results could be partly due to the stage of the disease at which the surgery is carried out. At present, surgery on patients with rheumatoid arthritis is undertaken at a stage in the disease where the muscles and the ligaments surrounding the joint, and the bone, are generally in a poor condition. Surgery at this stage is really only a salvage procedure. PMID- 7797960 TI - Fibrous stabilization of the rheumatoid wrist. AB - 19 patients (mean age 59.8 years) underwent fibrous stabilization of the wrist for rheumatoid arthritis. 17 patients were reviewed after a mean follow up of 24.5 months (range 13-40 months). There were four excellent, 11 good, and two poor results according to modified Koka and D'Arcy (1989) criteria. The poor results were due to deep infection in one patient and an unbalanced wrist due to ruptured radial extensors in another. The pre-operative range of wrist movement was an important determinant of the frequency of radio-carpal and/or mid-carpal fusion and the final post-operative range of movement. PMID- 7797957 TI - [Pathomechanism and treatment of cervical disc herniation]. PMID- 7797959 TI - Perichondrial arthroplasty incorporating costal cartilage. AB - A technique of IP joint arthroplasty is described using costal cartilage with accompanying perichondrium. All patients presented following trauma to the IP joints; their ages ranging from 15 to 45 years. Five out of six cases showed improvement of symptoms and function following reconstruction of the traumatized joint. PMID- 7797961 TI - Radiological evolution of the rheumatoid wrist after radio-lunate arthrodesis. AB - Radio-lunate arthrodesis of the rheumatoid wrist is an established technique which has been in use for more than 12 years. The evolution of 26 operated wrists and 20 non-operated wrists has been studied with a mean follow-up of 5 years. The results show that although radio-lunate arthrodesis can prevent dislocation of an unstable wrist, it cannot prevent deterioration. Collapse, ulnar translation, tilt of the lunate, and the inter-carpal instability continued with time, whether the wrists were operated on or not. The speed of deterioration was dependent on the type of rheumatoid arthritis and is faster in the disintegration type than in the osteoarthritis or the ankylosis type. The technique is applicable to the osteoarthritis type of rheumatoid arthritis, in the middle stage (2 to 4a according to the Larsen-Alnot classification). At that stage, the ankylosis type and the disintegration type, and the osteoarthritis type at an advanced stage, are better treated by total arthrodesis or total prosthetic arthroplasty. PMID- 7797962 TI - Distal ulnar instability following wrist arthrodesis in men. AB - 11 male patients with rheumatoid arthritis and 14 with osteoarthritis had total arthrodesis of the wrist. All patients with rheumatoid arthritis and ten (71%) of those with osteoarthritis had distal ulnar excision, two of the latter as a secondary procedure for impingement. Seven patients with osteoarthritis and none of the rheumatoid patients developed painful instability of the distal end of the ulna following excision. It is suggested that, in male patients with rheumatoid arthritis, distal ulnar excision with wrist arthrodesis produces excellent results with no complications. However, in male patients with osteoarthritis attempts should be made to avoid excessive shortening and ulnar impingement. If distal ulnar surgery is required, a procedure that does not affect the stability of the distal radio-ulnar joint should be performed rather than distal ulnar excision. PMID- 7797963 TI - Physical equilibrium of the normal wrist and its relation to clinically defined "instability". AB - The rotational stability of the proximal carpal row was tested on six unembalmed human cadaver hand specimens. The physiological load conditions were stimulated by loading the wrist flexor and extensor tendons. Pure torque was introduced to the lunate, scaphoid and triquetrum, one at a time, by means of a dynamometer wrench, forcing the bones loaded to perform a flexion-extension motion. A truly stable state of equilibrium could be found in the normal wrist only under axial load. A uni-directional coupling was observed through the scapho-lunate ligament as a counteraction to a tendency for the lunate to extend and the scaphoid to flex. The triquetrum and lunate moved together, showing close coupling in both directions. As conclusion: a stable wrist can be defined as one which, while being loaded within a physiological range of stress, does not deviate from a stable state of equilibrium (the ability to return to a single position when disturbed) at any point within the whole physiological range of motion. PMID- 7797964 TI - Wrist kinematics. Row, column or both? AB - Analysis of radiographs of 52 wrists showed that, from ulnar to radial deviation, the amount of scaphoid shortening and ulnar translation of the scaphoid varies in a normal distribution. There is a significant correlation between the two measurements, such that the more the scaphoid shortens the less it translates and vice versa. Females subjects were more likely to have greater scaphoid shortening and less translation. It is felt that carpal kinematics thus cover a spectrum from the "row" theory to the "column" theory which is normally distributed and that women are more likely to have a column type wrist. This variation may affect the result of treatment of scapholunate dissociation by techniques such as scapho lunate fusion. A "CR index" is proposed so that the tendency of a wrist towards row or column theory can be quantified. This may be used to predict the success of some surgical procedures in the treatment of scapho-lunate dissociation. PMID- 7797965 TI - The ulno-carpal abutment syndrome. Follow-up of the wafer procedure. AB - Seven wrists in six patients with ulno-carpal abutment syndrome were treated by a subchondral distal ulna resection (wafer procedure). The average follow-up was 36 months. Wrist function was evaluated using a clinical scoring chart. The parameters were pain, range of motion, grip strength and activities. One patient had a poor result, one a fair result and the remaining had good to excellent results. In all cases grip strength showed dramatic improvement. Complications were limited to palpable subcutaneous nylon sutures requiring removal in three patients and extensor carpi ulnaris tendinitis in one. PMID- 7797966 TI - A new technique of reattachment after traumatic avulsion of the TFCC at its ulnar insertion. AB - One female and seven male patients (median age 25.5) presented with traumatic avulsion of the triangular fibrocartilage complex (TFCC), type 1B according to Palmer's classification. Reattachment of the TFCC near its anchoring point was combined with an intraarticular shortening osteotomy of the ulnar head. This provides an excellent approach to the TFCC and a well vascularized anchoring surface. The mooring point is biomechanically appropriate and the tissues with the best biomechanical properties are used. The functional results with a mean follow-up of 3 years were encouraging, as demonstrated by the significant improvement of pain (P = 0.017). All patients were able to return to their previous occupation; no further surgery was necessary to the distal radio-ulnar joint and no impairment of pronation and supination was detected. The final wrist score reflects the subjective results defined by the patient. However the correlation is not linear and the wrist scores are superior to the degree of satisfaction defined by the patient. PMID- 7797967 TI - Open dislocation of the trapezoid. AB - Isolated dislocation of trapezoid is rare. We report here a new case of open dorsal dislocation of the trapezoid following a high energy crush injury of the left hand in a factory worker. It was associated with multidigital mutilation and metacarpal fractures. PMID- 7797968 TI - Pattern of scaphoid fracture union detected by macroradiography. AB - Stereoscopic macroradiography was used to study the pattern of union of scaphoid fractures. Of 21 patients who had partial union of a scaphoid fracture, 13 united on the ulnar side and five on the radial side only. In three it was on both sides but delayed in the centre. Where there was initial union on the ulnar side, all progressed to complete union, including two patients with displaced fractures. Four out of five patients with initial union on the radial side had displaced fractures, and three of these went on to non-union. We conclude that in those patients with partial union of a scaphoid fracture, if union is seen on the ulnar side, the fracture is likely to unite completely, whereas if there is partial union on the radial side, there is a high risk of non-union. PMID- 7797969 TI - Anterior wedge-shaped bone graft for old scaphoid fractures or non-unions. An analysis of relevant carpal alignment. AB - For appraisal of anterior wedge-shaped grafts for the humpback deformity of the scaphoid, a retrospective study of 27 cases with old scaphoid fractures or non unions was carried out. 11 cases were treated with Herbert screw fixation and anterior wedge-shaped graft and the other cases with other methods. For the assessment of carpal alignment, radio-lunate and scapho-lunate angles were measured with peri-operative radiographs. For the clinical assessment, the scoring system of Cooney was applied. In 25 cases, primary bone union was obtained with one attempt and in two cases, with the second operation. Union was achieved in a mean of 3.4 months. The post-operative wrist score ranged from 65 to 100 with an average 81.2 points. There was a statistically significant relationship between the wrist score and the post-operative scapho-lunate angulation of the affected wrist. The humpback deformity of scaphoid non-union should be treated precisely with carpal realignment surgery or anterior wedge shaped bone graft. PMID- 7797970 TI - Analysis of proximal fragment sclerosis and surgical outcome of scaphoid non union by magnetic resonance imaging. AB - 32 patients with scaphoid non-union were examined to clarify the relationship between pre-operative radiographic sclerosis in the proximal fragment and signal intensity on magnetic resonance imaging (MRI). In addition, the correlation between changes in signal intensity in the proximal fragment and surgical outcome after bone grafting and internal fixation was investigated. Proximal fragment sclerosis was observed in seven patients. Comparison of the T1 and T2-weighted images with those of the 25 patients without proximal fragment sclerosis revealed no differences. Therefore, there was no relationship between sclerotic changes on plain radiography and the degree of avascularity of the proximal fragment assessed by MRI. None of the patients who had low signal intensity on both T1 and T2-weighted images achieved union within 5 months after surgery. Thus the detection of signal intensity on both T1 and T2-weighted images can be useful to predict the prognosis after the surgery. PMID- 7797971 TI - Lunate dislocation with ulnar nerve paresis. PMID- 7797972 TI - Occult injury of the median nerve. AB - A case of median nerve injury caused by an unsuspected foreign body is described. The mechanism was not recognized at the time of injury. The suspicion of a penetrating missile injury was raised only with the aid of radiographs. At operation the foreign body was found in the substance of the median nerve. PMID- 7797973 TI - Low velocity gun shot wounds of the brachial plexus. AB - 28 patients with low velocity gunshot wounds of the brachial plexus were treated at Groote Schuur Hospital from 1980 to 1991. Delayed exploration of the brachial plexus (up to 7 months after injury) was performed in nine (30%) of the patients. The other 19 patients did not have exploration of the plexus; most of these patients showed signs of recovery within 2 to 4 weeks of injury. Injury to the subclavian or axillary artery occurred in nine (30%) of the cases. The average length of follow-up of the patients was 19 months (range 2-90 months). Of the 19 patients treated non-operatively, 15 (79%) had an excellent or good result and four (21%) a fair result. The indications for surgery were the absence of improvement within 3 months of injury or persistent pain. Surgery was indicated for significant pain in five of the nine patients; postoperatively two had complete relief of pain, two improvement in the pain and one no improvement. Of the nine surgically treated patients, three (33%) had a good result, two (22%) a fair result and four (45%) a poor result. The potential for recovery was not dependent on the severity of the injury at presentation or the presence of vascular injury but on the appearance of signs of recovery within 4 weeks of injury. PMID- 7797974 TI - Vascularized pedicle graft of the lower trunk for reconstruction of the branchial plexus. AB - The middle trunk of an injured brachial plexus was reconstructed using a vascularized graft of the lower trunk, which was expendable because of irreparable damage to the C8 and T1 nerve roots. The graft was transferred on a vascular pedicle of mesoneurium. Useful recovery was achieved at 3 years. This technique helps to overcome the problems of limited supply and secondary sensory deficit of grafts from peripheral nerves, but is possible only if the plexus is explored early, before mobilization and transfer of nerve trunks is precluded by scarring. PMID- 7797975 TI - Digital nerve compression by hyperplastic Pacinian corpuscles. A case report and immunohistochemical study. AB - A 68-year-old lady developed digital pain within days of the excision of a palmar ganglion. This was found to be due to a mass of hyperplastic Pacinian corpuscles compressing the digital nerve. Immunohistochemistry was carried out on the resected corpuscles using antisera to a range of neuropeptides. Possible mechanisms of hyperplasia are discussed. PMID- 7797976 TI - Risk and complications in endoscopic carpal tunnel release. AB - Single portal endoscopic carpal tunnel release was carried out in 107 hands of 88 patients. There were 11 complications. These included incomplete release (2), post operative scarring around the median and ulnar nerves (2), laceration of the superficial palmar arterial arch (1), reflex sympathetic dystrophy (2), palmar fasciitis (1), and wound inflammation (3). In two cases there was no relief of symptoms. In one there was incorrect diagnosis and in another, incorrect indication for endoscopic carpal tunnel release. The follow-up was from 3 to 18 months with an average of 6.8 months. The overall results of the patients in this series are being presented in another paper. Of the 107 procedures, 73 were rated as having an excellent, 25 good, three fair, and six poor results. The case of laceration of the superficial palmar arterial arch is discussed in detail in the paper. The two cases of reflex sympathetic dystrophy and the one case of palmar fasciitis had mild clinical features and resolved within 3 months. The inflammation in three of the wounds at the wrist resolved within 2 days of removal of the percutaneous sutures. These three patients had returned to heavy hand activities within a few days of surgery. PMID- 7797977 TI - Early mobilization following carpal tunnel release. A prospective randomized study. AB - A prospective randomized study was undertaken of 50 consecutive patients undergoing surgery for idiopathic carpal tunnel syndrome to determine the value of splintage of the wrist following open carpal tunnel release. Patients were randomized to either be splinted for 2 weeks following surgery or to begin range of-motion exercises on the first post-operative day. Subjects were evaluated at 2 weeks, 1 month, 3 months, and 6 months after surgery by motor and sensory testing, physical examination, and a questionnaire. Variables assessed included date of return to activities of daily living, dates of return to work at light duty and at full duty, pain level, grip strength, key pinch strength, and occurrence of complications. Patients who were splinted had significant delays in return to activities of daily living, return to work at light and full duty, and in recovery of grip and key pinch strength. Patients with splinted wrists experienced increased pain and scar tenderness in the first month after surgery; otherwise there was no difference between the groups in the incidence of complications. We conclude that splinting the wrist following open release of the flexor retinaculum is largely detrimental, although it may have a role in preventing the rare but significant complications of bowstringing of the tendons or entrapment of the median nerve in scar tissue. We recommend a home physiotherapy programme in which the wrist and fingers are exercised separately to avoid simultaneous finger and wrist flexion, which is the position most prone to cause bowstringing. PMID- 7797978 TI - The provision of innervated skin cover for the injured thumb using dorsal metacarpal artery island flaps. AB - Provision of stable sensate skin is of great importance in reconstruction of the injured thumb. Island flaps based on the dorsal metacarpal arteries were used to resurface ten injured thumbs, and the degree of retained sensibility was assessed using static and moving two-point discrimination and the pick-up test. Results show that these flaps are capable of providing stable full-thickness skin cover in a single procedure and functional sensibility is retained in most cases. The second dorsal metacarpal artery island flap, previously advocated for use in small thumb defects only, has been successfully used as a large wraparound flap in two cases. In one of these it was used with free bone graft to increase the length of the thumb and an excellent functional result was achieved. PMID- 7797980 TI - Comparison of ulnar and radial arterial blood-flow at the wrist. AB - Historical descriptions of the ulnar artery as the dominant vessel to the hand appear to be inconsistent with clinical experience. Anatomical dissections and radionucleotide flow studies of the ulnar and radial arteries at the wrist were performed. These failed to demonstrate any difference between the anatomical dimensions of these vessels, but the radial artery was shown to have a statistically greater blood flow compared to the ulnar artery. This finding suggests that, contrary to popular opinion, the radial artery is the dominant vessel to the hand. PMID- 7797979 TI - Cold-induced vasospasm after digital replantation does not improve with time. A 12-year prospective study. AB - The incidence of cold-induced vasospasm after hand injuries has been reported to be as high as 100%, following replanted digital amputations. The exact cause of this problem is obscure, no specific treatment is available and little is known about the long-term prognosis. Further knowledge is therefore needed in order to advise patients concerning future job potential at an early stage. In a previous paper we evaluated the incidence and severity of cold intolerance 2 years after digital replantation. The incidence of cold-induced vasospasm then was high as well as the discomfort experienced by the patients. We carried out a follow-up of patients previously examined 10 years ago. Our results show that cold induced vasospasm in replanted digits does not improve with time. Patients with moderate symptoms may perceive improvement, probably due to a change of habits. Patients with severe problems did not experience improvement and should be given early advice to seek work in warm surroundings to reduce the discomfort. PMID- 7797981 TI - Traumatic avulsion of the ulnar collateral ligament of the IP joint of the thumb. AB - We present a previously undescribed injury of avulsion of the ulnar collateral ligament of the thumb IP joint. Stress radiographs may be used to confirm the diagnosis in cases of clinical suspicion. PMID- 7797982 TI - Bone suture anchors in hand surgery. AB - The recent development of small bone suture anchors has created potential applications in reconstructive surgery of the hand and wrist. A combined laboratory and clinical study was devised to evaluate their use. 16 paired fingers (32 in all) from eight cadaveric hands were disarticulated at the MP joint with a 10 cm tail of FDP tendon. The FDP insertion was released in all specimens. In 16 fingers reinsertion was performed with the classic Bunnell technique; in the paired 16 fingers, the repair utilized Acufex 2 mm anchors. There was no significant difference between the two groups regarding load-to failure at approximately 40 Newtons. The mean stiffness of the anchor repairs was significantly greater than the Bunnell repairs. 19 consecutive patients were prospectively enrolled with a tendon or ligament repair of the hand or wrist using bone anchors. The average age was 41 years and the average length of follow up was 24 months. All repairs were stable at the time of follow-up. Bone anchors were simple to insert, required less dissection and surgical time than the Bunnell technique and appeared to be reliable in both laboratory and clinical settings. PMID- 7797983 TI - Combined fourth and fifth metacarpal fracture and fifth carpometacarpal joint dislocation. AB - Three cases of hamato-metacarpal fracture-dislocation with fracture of the shaft or base of the fourth metacarpal and dorsal dislocation of the fifth metacarpal are described. In one case this was associated with coronal fracture of the hamate. An oblique radiograph of the hand with the forearm pronated 15 degrees and 45 degrees provided a good view of the extent of the fourth and fifth carpometacarpal injury. Treatment with open reduction and internal fixation achieves good clinical results. PMID- 7797985 TI - Swan-neck deformity as a complication of the Agee technique. AB - Unstable dorsal fracture dislocations of the PIP joint of a finger commonly result in joint stiffness following immobilization or open reduction and internal fixation (Green and Rowland, 1984). The Agee dynamic external fixator, or force couple splint (Agee, 1978; 1987), was introduced in an attempt to avoid this complication and maintains a concentric reduction whilst allowing a full range of joint movement. The splint is constructed from three Kirschner wires and is activated by a single rubber band. A force couple is created across the proximal interphalangeal joint levering the base of the middle phalanx towards the palm whilst simultaneously lifting the distal end of the proximal phalanx dorsally to restore joint reduction. However, this technique is not without complications (Agee, 1987). We report a swan-neck deformity resulting from this treatment. PMID- 7797986 TI - Injuries to the nail bed in childhood. AB - Many fingertip injuries in childhood involve the nail bed. Deformities of the nail are a frequent result of failure to repair the nail bed at the time of injury. Secondary correction of nail deformities seldom achieves good results. We present the results of our experience in the management of 19 children with 22 injuries involving the nail bed. All achieved normal nail growth and the overall result of the repair was good in 91%. Complications were few and parental satisfaction with the management was high. Every effort should be made to perform a meticulous primary repair of all nail bed injuries. PMID- 7797984 TI - Double dislocation of the fifth metacarpal. AB - A case of traumatic, simultaneous, double dislocation of the fifth metacarpal bone is presented. Closed reduction was easily achieved and held with transarticular, crossed Kirschner wire fixation. PMID- 7797987 TI - Dorsal intercalated segment instability (DISI) and scapho-trapezio-trapezoid (STT) osteoarthritis. PMID- 7797988 TI - The acoustic neuroma saga. PMID- 7797989 TI - 'A brilliant surgical result, the first recorded': Annandale's case, 3 May 1895. PMID- 7797990 TI - Hearing preservation in vestibular schwannoma surgery: fact or fantasy? AB - This study reviews 57 papers dealing with the issue of hearing preservation in vestibular schwannoma surgery published in otolaryngologic and neurosurgical literature between the years 1977 and 1994. The authors', in this review, have made an attempt to verify whether the claims of hearing preservation are real, whether there is a price to be paid in terms of morbidity and whether there are univocal criteria for reporting results. The review shows that there is a wide disarray in reporting hearing results and the claims of hearing preservation are often unreal and misleading. On retabulating the results of a few series according to the minimal prerequisites for normal hearing (PTA < or = 30 dB and SDS > or = 70 per cent) and according to other various commonly reported criteria, it became evident that rates of hearing preservation differed a lot depending upon criteria. While any measurable hearing could be preserved in many cases, only a few had normal hearing preserved. PMID- 7797991 TI - The molecular genetics of 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 acts as a tumour suppressor. The results of recent research in Cambridge suggest that somatic mutations of the NF2 tumour suppressor gene are a critical step in the pathogenesis of both familial and indeed non-familial unilateral sporadic vestibular schwannoma and that the mechanism of tumourigenesis complies with the 'two-hit' model. This paper represents a brief review of the current status of molecular biology in relation to vestibular schwannoma in particular and is discussed in relation to the molecular pathology of skull base tumours as a whole. PMID- 7797992 TI - The restoration of hearing in neurofibromatosis type 2. AB - Central electrical stimulation of the auditory pathway can allow hearing in patients suffering from deafness localized in the auditory nerve. Developments in a multi-channel auditory brainstem implant based on the Nucleus Mini 22 Cochlear implant with transcutaneous signal transmission is discussed. The devices have been implanted in nine European patients suffering from Neurofibromatosis Type 2. Preliminary speech perception results and patient satisfaction are encouraging, and the data presented include some limited open speech recognition. PMID- 7797993 TI - Middle ear pressures in patients with nasopharyngeal carcinoma and their clinical significance. AB - There is a paucity of studies investigating middle ear pressures (MEPs) in patients with nasopharyngeal carcinoma (NPC). This paper prospectively examines MEPs in patients with nasopharyngeal carcinoma before and after radiotherapy and discusses their clinical significance. Newly diagnosed patients with nasopharyngeal carcinoma were studied before and at three to 12 months (mean 7.5 months) after radiotherapy. MEPs were measured by tympanometry. Thirty-three patients completed the study. The mean MEP before and after radiotherapy was 55.2 mm water (range -250 to 45 mm water) and -73.1 mm water (range -215 to 35 mm water) respectively. About two-thirds of assessable ears had an increase in negative MEPs after irradiation and the rest had less negative MEPs after irradiation. Those ears which developed post-irradiation middle ear effusions were found to have pre-irradiation negative middle ear pressures of at least -45 mm water. These findings provide possible explanations for some unexplained audiometric observations previously made in patients with nasopharyngeal carcinoma after radiotherapy. Tympanometry before radiotherapy may prove to be useful in identifying ears with a high risk of developing post-irradiation middle ear effusion. PMID- 7797994 TI - Role of magnetic resonance imaging in predicting late facial motor function after removal of vestibular schwannomas by the translabyrinthine approach. AB - Facial motor function was assessed in 61 patients 18 months after surgical resection, by the translabyrinthine approach, of vestibular schwannoma involving both the cerebellopontine angle (CPA) and the auditory canal. Pre-operative magnetic resonance imaging (MRI) was performed to measure the maximum extracanalicular diameter of the tumour between the porus and the farthest extension in the CPA on transverse slices and to calculate extracanalicular tumour volume. Post-operative facial motor function was graded according to the House and Brackmann system. There was a statistically significant relationship between late facial motor function and extracanalicular diameter. The best cut off point for good and poor results was 20mm. There was no relationship between the tumour volume and the late post-operative facial motor function grade. In this study the best pre-operative radiological predictor of the late facial motor function in patients operated on by the translabyrinthine approach was the maximum diameter measured by MRI. PMID- 7797995 TI - An evaluation of mucus glycoproteins in the larynges of victims of sudden infant death syndrome. AB - Larynges from 24 victims of Sudden Infant Death Syndrome (S.I.D.S.) and 10 controls, with ages ranging from two days to 24 weeks in the controls and from two to 116 weeks in the S.I.D.S. victims, were transversely, step-serially sectioned and then stained to show acid, neutral and mixed mucus glycoproteins. The proportion of sulphated mucus glycoprotein and sialylated mucus glycoprotein to total acid mucus glycoprotein was determined by the use of various staining techniques and a comparison was made for each type between S.I.D.S. and controls. The differences were significant with a mean of 27 per cent in the controls compared to 59 per cent in the S.I.D.S. for sulphomucin (difference 32 per cent; standard error of difference 6 per cent; p < 0.01) and 73 per cent in the controls compared to 41 per cent in the S.I.D.S. larynges (difference 32 per cent; standard error of difference six per cent; p < 0.01) for sialomucin. The results suggest that sulphated mucus glycoprotein is secreted in excess in some victims of Sudden Infant Death Syndrome. PMID- 7797996 TI - Evolution of speech and voice following supracricoid partial laryngectomy. AB - The evolution of voice and speech parameters following supracricoid partial laryngectomy (SCPL) has been evaluated in a prospective fashion over an 18-month period of time in three patients using the Computerized Speech Lab (from Kay Elemetrics). Preliminary results demonstrate the post-operative instability of voice parameters. Speech parameters remain stable with time. Our data stresses that voice is attained post-operatively even if one arytenoid cartilage is disarticulated at time of resection. PMID- 7797997 TI - A comparison between two methods of measuring pressure in the pharyngeal airway: transducer probe versus open catheter. AB - A new multi-transducer probe system for measuring pharyngeal pressures was compared with an established open catheter system. Pharyngeal pressure measurements were made at the same time, and site, in subjects awake, at unmodified and with artificially increased nasal airway resistances, and during sleep documented by polysomnography. The two systems yielded almost identical results. It is anticipated that the multi-transducer probe system will prove of clinical value. PMID- 7797998 TI - Multidisciplinary management of dysphagia: the first 100 cases. AB - A report of the first 100 patients treated in the multidisciplinary Dysphagia Clinic in Salisbury District Hospital is presented. It was established in January 1992 and involves the Departments of ENT Surgery, Clinical Radiology and Speech and Language Therapy. In the first 18 months, 100 patients have been assessed and treated. These included 46 males and 54 females, between the ages of four and 93 years. Neurological problems accounted for 39 cases. The management comprised the assessment clinic, videofluoroscopy in 83 patients, and finally the appropriate treatment. Forty-four patients were treated primarily by swallowing therapy. Seventy-three patients showed complete recovery, resolution of their symptoms or did not require treatment. Two patients were still under treatment at the time of writing this paper. PMID- 7797999 TI - Cochlear implant extrusion in a young child--a preventive procedure. AB - A Cochlear Mini System 22 Channel cochlear implant extruded through the skin of a young girl. The implant was saved by use of a transposition flap. Extrusion appeared to be due to pressure necrosis from the implant on the overlying tissues. It is believed that this problem can be prevented by angulation of the implant before insertion so that it conforms to the curvature of the skull, so avoiding pressure on the tissues. The method of angulation is described. PMID- 7798000 TI - Thrombosed posterior-inferior cerebellar artery aneurysm: a rare cerebellopontine angle tumour. AB - A case report of a thrombosed posterior-inferior cerebellar artery aneurysm is described. The tumour masqueraded as a vestibular schwannoma on imaging but the presenting features were unusual, the facial pain and weakness predominating despite well preserved hearing. This is an example of a rare cerebellopontine angle tumour and highlights the need for suspicion when lesions present atypically. PMID- 7798001 TI - Verbal auditory agnosia with focal EEG abnormality: an unusual case of a child presenting to an ENT surgeon with "deafness". AB - Verbal auditory agnosia implies the failure to recognize sounds in a patient who is nevertheless not deaf. We present a child referred to the ENT outpatients for suspected hearing loss investigation. At one point she had grommets inserted on the basis of a flat tympanogram but with no effect. All hearing tests, including electrocochleography and distraction tests, revealed normal hearing thresholds. At the age of three years and three months, and on direct questioning of the parents, we discovered that the child responded remarkably well to music. Paediatric neurologists made the diagnosis of verbal auditory agnosia. The condition is very similar to another acquired language disorder called Landau Kleffner syndrome. It is unusual for such a case to present primarily to an ENT surgeon. PMID- 7798003 TI - Bleeding after tonsillectomy in severe von Willebrand's disease. AB - A case is reported of a HIV-positive patient with severe von Willebrand's disease describing the bleeding complications during and after tonsillectomy. This patient underwent surgery for asymmetrical tonsillar hypertrophy. The tonsils were spontaneously haemorrhaging and there therefore was a suspicion of neoplasia. Despite close cooperation between the ENT Department and the Haemophilia Centre, involving per-operative Factor VIII monitoring and replacement, the patient suffered both protracted primary and secondary haemorrhages. We report this as a cautionary tale as our previous experience with mild to moderate haemophilia has been uncomplicated, but on this occasion there was massive haemorrhage. We feel that tonsillectomy should not be undertaken in a patient with a severe bleeding disorder without an absolute indicate. PMID- 7798002 TI - Inherited degenerative chondropathy--an autosomal dominant new clinical entity: report two cases and follow-up of four cases. AB - Four cases of the rare disorder, inherited degenerative chondropathy have been previously reported (Kurien et al., 1989). A five-year follow-up of these patients and two additional cases are presented in this report. The progress of this disease appears to be arrested after regular dapsone therapy and there was no other organ involvement noted during the follow-up period. PMID- 7798004 TI - Tension pneumoperitoneum as an early complication after adenotonsillectomy. AB - Pneumoperitoneum as a result of pneumomediastinum has been described already. Amongst the causes pneumoperitoneum due to a complication of adenotonsillectomy, has not previously been described. We describe a five-year-old girl with tension pneumoperitoneum with respiratory and circulatory insufficiency half an hour after adenotonsillectomy. Removal of the intra-abdominal air with a 14 gauge needle restored normal respiration and circulation. PMID- 7798005 TI - The use of leeches in a case of post-operative life-threatening macroglossia. AB - A case of severe macroglossia, following intraoral surgery, causing respiratory distress is described. Because conventional therapy appeared inadequate, leeches were used and proved an efficient method of reducing this life-threatening swelling of the tongue. PMID- 7798006 TI - Heterotopic pleomorphic adenoma in the neck. AB - Cervical heterotopic salivary tissues are rare and are predominantly found in the anterior triangle of the neck especially at the anterior border of the sternocleidomastoid muscle. We report a case of pleomorphic adenoma arising in the left posterior triangle of the neck. PMID- 7798007 TI - Computed tomographic findings in peritonsillar abscess and cellulitis. AB - The differentiation of a peritonsillar abscess from peritonsillar cellulitis, although difficult on physical examination, is required in order to determine the appropriate treatment. Peritonsillar cellulitis can be treated with antibiotics alone, while a peritonsillar abscess should be drained. Computed tomography (CT) of the neck is often performed to identify the formation of a deep abscess in the neck, but is rarely used to diagnose peritonsillar infections. We report a patient in whom CT was a useful diagnostic tool for distinguishing peritonsillar abscess from peritonsillar cellulitis. PMID- 7798008 TI - The value of radiographic assessment for oropharyngeal foreign bodies. AB - A double-blind, controlled study to assess the accuracy of interpretation of lateral soft tissue radiographs of 60 patients with suspected foreign body impaction in the oro/hypopharynx was carried out by 18 respondents from three different specialities. All the patients had endoscopy carried out and foreign bodies were present in 25. Of these, foreign bodies were diagnosed on the radiograph in only 38.3 per cent. False-positive diagnoses were made in a mean of 26.3 per cent of those patients who did not have a foreign body. PMID- 7798009 TI - Atypical carcinoid tumour of the larynx. AB - The case of an atypical carcinoid tumour of the larynx is described in a 65-year old man. This rare tumour may present diagnostic difficulties, but the diagnosis should be considered in a patient presenting with symptoms of local or referred pain and an apparently small, non-ulcerating supraglottic tumour. Immunocytochemistry has an important role in establishing the diagnosis. A very unusual feature of this case was positive staining for S-100 protein by sustentacular cells. Atypical carcinoid tumours do not respond well to radiotherapy so the primary treatment should be surgical resection. PMID- 7798010 TI - Polypoidal carcinosarcoma of the oropharynx: a clinicopathological and immunohistochemical study. AB - Polypoidal squamous cell carcinomas, with a sarcomatous stroma, in the upper aerodigestive tract are very rare but well described tumours. They are associated with a multifarious nomenclature because of different opinions regarding their histology and histogenesis. The main issue is whether the stroma component is a true sarcoma or a benign reactive lesion. In order to draw the attention of otolaryngologists and pathologists to the characteristic features of this rare tumour, two cases originating from the oropharynx are presented. Both tumours were pedunculated and polypoidal, and their bulk consisted of a bizarre sarcoma like stroma covered with granulation tissue. In some areas of the surface, however, atypical squamous cell epithelium with foci of invasive carcinoma was found. In the vicinity of the latter both tumours contained areas of adenocarcinoma. After surgical excision followed by radiation therapy, there was no recurrence after two and five years, respectively. The histological and immunohistochemical findings support the assumption that these two tumours are carcinosarcomas. Adenocarcinomatous elements in this type of tumour have to our knowledge been reported only twice previously and have never been observed in the pharynx. PMID- 7798011 TI - Terminal duct adenocarcinomas of the parotid gland. AB - The major salivary glands are considered to rarely be the sites of primary terminal duct adenocarcinomas, a neoplasm with a considerable predilection for origin from intraoral minor salivary glands. We present a clinicopathological study of 22 terminal duct adenocarcinomas of the parotid gland, the largest single series to date. A comparison between the parotid neoplasms and over 200 minor salivary gland terminal duct adenocarcinomas indicates there is little difference in biological behaviour and confirms the low-grade quality of the carcinomas, regardless of site of origin. PMID- 7798012 TI - Button batteries. PMID- 7798013 TI - Metastatic papillary thyroid carcinoma: an important differential diagnosis for aberrant thyroglossal cyst. PMID- 7798014 TI - Transport of protein hormones through the vascular endothelium. PMID- 7798015 TI - The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring. AB - The effect of maternal diabetes mellitus on renal calcium excretion in pregnant rats and their offspring has been examined in order to ascertain the role of the kidney in the disturbed calcium homeostasis of infants born to diabetic mothers. Diabetic pregnant (DP) rats exhibited severe hypercalciuria which greatly exceeded the urinary calcium losses (UCaV) in non-diabetic pregnant (CP) or non pregnant diabetic (D) rats. Means +/- S.E.M. for UCaV at day 21 (mmol/24 h) were: DP = 1.12 +/- 0.09 (n = 7); CP = 0.06 +/- 0.01 (n = 7); D = 0.63 +/- 0.06 (n = 7) (P < 0.001 DP vs CP and DP vs D). The profile for urinary calcium excretion in the three groups was different from that of other measured ions. The degree of natriuresis, for example, was comparable in DP and D rats at all stages studied. Although magnesium output was significantly greater in DP than D rats on days 14 and 21, this appeared to result from an additive effect of the magnesiuresis seen when pregnancy and diabetes were studied separately. The marked renal calcium wasting of diabetic pregnancy will have implications for overall calcium balance in the mother. For example, an enhanced intestinal calcium absorption was seen in DP rats in the second half of gestation. Means +/- S.E.M. for day 21 (mmol/24 h) were: DP = 3.8 +/- 0.8 (n = 7); CP = 1.4 +/- 0.3 (n = 7); D = 1.6 +/- 0.3 (n = 7) (P < 0.05 DP vs CP and DP vs D).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798017 TI - IGF-I administration advances the decrease in hypersensitivity to oestradiol negative feedback inhibition of serum LH in adolescent female rhesus monkeys. AB - Developmental increases in serum LH were assessed in female rhesus monkeys to test the hypotheses that (1) the final stages of puberty are characterized by a decrease in hypersensitivity to oestradiol negative feedback of LH and (2) that increases in IGF-I secretion accelerate this decrease in hypersensitivity. In order to test the first hypothesis, serum LH in the absence of oestradiol and in response to three doses of oestradiol were compared between ovariectomized adult (n = 6) and adolescent female monkeys (control group; n = 6). The control females were not treated with oestradiol until serum LH had risen to within the 95% confidence interval of serum LH observed in ovariectomized adults. Doses of oestradiol achieved serum levels of approximately 80 ('low'), 160 ('intermediate'), and 250 ('high') pmol/l. For control group females, treatment with the next higher dose of oestradiol was not initiated until serum LH was no longer suppressed by the lower dose. Treatment with oestradiol produced a dose dependent suppression in serum LH in adults. In contrast, low-dose oestradiol maximally suppressed serum LH throughout the initial treatment period in the control group compared with the adult females. The low oestradiol dose effectively suppressed serum LH throughout the study period in 4/6 of the control group and became ineffective at suppressing LH after 8 months of treatment in 2/6 control group females. Initiation of the intermediate dose of oestradiol to these females again maximally suppressed LH compared with adult females. In order to determine whether IGF-I regulates this change in hypersensitivity to oestradiol negative feedback, a second group of ovariectomized, adolescent monkeys (n = 6) were treated chronically with IGF-I to elevate serum IGF-I levels above those of control group females. Using the same protocol described for the control females, developmental changes in serum LH in the absence of oestradiol and in response to oestradiol negative feedback were evaluated. Treatment with IGF-I had no effect on the initial increases in serum LH occurring in the absence of oestradiol. In contrast, the decrease in hypersensitivity to the negative feedback effects of the low oestradiol dose was significantly accelerated in IGF-I-treated females, as the interval from the initiation of treatment to the point at which serum LH was no longer suppressed was shorter in IGF-I-treated (4.4 +/- 0.7 months; mean +/- S.E.M.) compared with control group females (8.4 +/- 1.9 months).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798016 TI - Oxytocin modulates the luteinizing hormone response of the rat anterior pituitary to gonadotrophin-releasing hormone in vitro. AB - Although GnRH is believed to be the primary secretagogue for LH, oxytocin has also been shown to stimulate LH release from the anterior pituitary. We investigated the possibility that the two secretagogues interact in the modulation of LH release. Anterior pituitaries were removed from adult female rats at pro-oestrus, and tissue pieces were pre-incubated in oxytocin for 3 h prior to being stimulated with 15 min pulses of GnRH. LH output over the 1 h period from the beginning of the GnRH pulse was determined. Control incubations were carried out in the absence of oxytocin, and background secretory activities without GnRH stimulation were also determined. Tissue which was pre-exposed to oxytocin (0.012-1.25 microM) had an increased LH response to GnRH (1.25 nM). The increase was larger than the sum of the LH outputs obtained with oxytocin and GnRH separately, revealing that oxytocin synergistically enhanced LH secretion elicited by GnRH (P < 0.05; ANOVA). If stimulation by GnRH was delayed for 2 h after incubation with oxytocin, an increase in LH secretion was still observed, indicating that oxytocin-induced modulation did not rapidly disappear. Oxytocin pre-incubation was observed to result in an increase of maximal GnRH-induced LH output (P < 0.001; t-test), as well as an increase of intermediate responses. The LH response of the anterior pituitary to subsequent pulses of GnRH was modified by the self-priming process. The effect of oxytocin pretreatment on the response of primed tissue to GnRH was also investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798019 TI - Peptide amidating activity and gastrin processing in the developing sheep pancreas. AB - Gastrin is a regulator of both gastric acidity and gastrointestinal growth and is expressed transiently in the neonatal ovine and human pancreas. C-terminal amidation of glycine extended gastrin (G-gly) to gastrin amide (G-amide) by peptidylglycine alpha-amidating mono-oxygenase (PAM) is the final processing step. To investigate the relationship between PAM and gastrin synthesis in the developing pancreas, we measured PAM activity and the concentrations of gastrins in ovine pancreatic extracts from 95 days of gestation onwards. Pancreatic PAM activity was highest in the 95-day-old fetus (138 +/- 29 pmol/h/mg protein, mean +/- S.E.M.) and decreased to 9.5 +/- 3.7 pmol/h/mg protein in the adult. The circulating enzyme was also highest in the youngest fetus (1840 +/- 165 pmol/h/ml plasma) decreasing to approximately 50% in the 135-day-old fetus, with no further significant changes. The concentration of bioactive G-amide in the pancreas was 2.0 +/- 0.6 pmol/g at 95 days of gestation, 3.4 +/- 0.9 pmol/g at 135 days and decreased to 0.7 +/- 0.1 pmol/g in the adult. The precursor G-gly followed a similar pattern but its concentration was less than 10% of G-amide. These results show that: (a) there are high levels of PAM activity in the ovine fetal pancreas and in the fetal circulation, (b) PAM activity is apparently not rate-limiting in the bioactivation of pancreatic gastrin and (c) the dual expression of both PAM and gastrin in the fetal pancreas is similar to that observed in peptide secreting tumours of the adult. PMID- 7798018 TI - Effects of thyroid hormone on coenzyme Q and other free radical scavengers in rat heart muscle. AB - Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2 . These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat. PMID- 7798020 TI - Starvation-induced changes in the hypothalamic content of prothyrotrophin releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland. AB - The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone. PMID- 7798021 TI - Effect of glycoprotein and protein hormones on human meningioma cell proliferation in vitro. AB - Speculation that meningiomas are subject to female hormone influence is supported by their higher incidence in women and reports of exacerbation of symptoms during pregnancy and the luteal phase of the menstrual cycle. Previous reports have concentrated on the effects of the steroid hormones oestradiol and progesterone on meningioma proliferation. In this study we have investigated the roles of the glycoproteins LH, FSH and human chorionic gonadotrophin (hCG), and the protein hormones prolactin (PRL) and human placental lactogen (hPL) on the proliferation of human meningiomas in vitro. The three glycoproteins had an inhibitory effect on meningioma proliferation ranging from 5.0-50.0%, 10.0-63.0% and 2.4-34.0% at the highest concentrations of LH (25 mIU/ml), FSH (15 mIU/ml) and hCG (30 IU/ml) respectively. Cultures were also treated with PRL (100 and 200 ng/ml) and hPL (5 and 10 ng/ml) and the protein hormones had a stimulatory effect on cell proliferation of 12.0-55.5% and 11.4-73.6% when treated with 200 ng/ml PRL and 10 micrograms/ml hPL respectively. Our data suggest that increasing levels of the protein hormones PRL and hPL, falling levels of hCG and the absence of LH and FSH in the second and third trimesters of pregnancy may play a role in the acceleration of meningioma growth in these stages of pregnancy. PMID- 7798022 TI - Augmentation of the effectiveness of porcine GH with swine antibodies induced by a synthetic GH peptide. AB - An effort was made to evaluate the potential usefulness of a peptide vaccine in improving the growth performance of farm animals. It was previously reported that a murine PS-7.6 monoclonal antibody (mAb) which was specific to porcine GH (pGH) enhanced the growth-promoting activity of pGH in an experimental hypophysectomized rat model. Additional data from a epitope mapping study suggested that PS-7.6 mAb recognized a pGH fragment corresponding to an amino acid sequence 54-95. In this report, therefore, a peptide pGH(54-95) was synthesized in an attempt to induce PS-7.6-like antibodies in swine. It was demonstrated that the peptide pGH(54-95) competed with PS-7.6 mAb for the binding to radioactive pGH in a competition radioimmunoassay and also caused pigs to elicit polyclonal antibodies immunoreactive to pGH protein. The association and dissociation rate constants of the swine antibody to pGH were 1.9 x 10(2) M-1 s-1 and 3.2 x 10(-4)s-1 respectively, thus producing an overall binding affinity of Kd = 1.6 x 10(-6) M. The swine antibody partially competed with murine PS-7.6 mAb for the binding to pGH, suggesting that the pGH-recognizing sites for both antibodies might be closely related. The biological effect of the swine antibody was examined in hypophysectomized rats and shown to significantly augment pGH activity in promoting the growth of these GH-deficient animals. The present findings suggest that a synthetic peptide may be developed as a potential growth vaccine for swine to generate antibodies capable of enhancing the effectiveness of endogenous pGH. PMID- 7798023 TI - Epitope mapping and analysis of a growth-enhancing monoclonal antibody by limited tryptic digestion of porcine GH. AB - In this study, the epitope of a murine PS-7.6 monoclonal antibody (mAb) which was raised against the recombinant porcine GH (pGH) and subsequently shown to enhance the growth-promoting activity of pGH in a hypophysectomized rat model, was mapped by the limited tryptic digestion of pGH. A pGH fragment corresponding to amino acid residues 70-95 was separated by reverse-phase HPLC and also immunoprecipitated by PS-7.6 mAb. This fragment was found in an RIA to compete with radiolabelled pGH for the binding of PS-7.6 mAb in a dose-dependent fashion. Several peptides covering this potential epitope region of pGH(70-95) were synthesized and assayed by competitive RIA. The results suggested that pGH(75-90) was the optimal sequence recognized by PS-7.6 mAb. Sequential alanine substitution of each residue of pGH(75-90) revealed that the side chains of Leu76, Ile83 and Leu87 were critical for binding to PS-7.6 mAb. Other residues could be replaced by alanine without substantially altering the binding affinity. The region of amino acids 75-95 comprises the C-terminal end of the second helix of pGH and the repeating pattern of i and i + 3 (i + 7) of the critical amino acids appears consistent with PS-7.6 mAb binding to the hydrophobic side of the helix. The sequence and the helical structure of the epitope of PS-7.6 mAb provide the basis for designing the effective peptide vaccines to enhance the growth performance of animals. PMID- 7798024 TI - Effect of the level of oestradiol on oxytocin-induced prostaglandin F2 alpha release in the cow. AB - We have investigated the effects of oestradiol-17 beta on the development of the luteolytic signal (prostaglandin F2 alpha (PGF2 alpha) release to an oxytocin challenge) using a steroid-treated ovariectomised cow model. Long-term ovariectomised cows were pre-treated with progesterone for 14 days followed by oestradiol-17 beta for 2 days to induce oestrus (day 0), and were then treated for a further 16 days with physiological doses of progesterone and oestradiol-17 beta to simulate a luteal phase. On day 11 oestradiol was either withdrawn (low group; n = 4), maintained (normal group; n = 4) or increased (high group; n = 4), generating mean (+/- S.E.M.) plasma concentrations of oestradiol from days 12-16 of 0.9 +/- 0.1, 2.3 +/- 0.4 and 3.7 +/- 0.2 pg/ml respectively. Basal and oxytocin-stimulated PGF2 alpha secretion was monitored by measuring concentrations of the principal metabolite of PGF2 alpha, 13,14-dihydro-15-keto PGF2 alpha (PGFM), in plasma samples collected before and after daily i.v. injection of 50 IU oxytocin from days 12-16. Basal PGFM was unaffected by the level of oestradiol treatment. In the normal group significant rises in plasma PGFM were seen following oxytocin on days 12, 13 and 14 (P < 0.05) as well as days 15 and 16 (P < 0.01). In the low group significant elevations in PGFM were only seen on days 15 and 16 (P<0.05), and were smaller (P<0.05) than those seen in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798025 TI - Corpuscles of Stannius and blood flow regulation in freshwater North American eels, Anguilla rostrata LeSueur. AB - Cardiac output (CO), heart rate (HR), stroke volume (SV), dorsal aortic blood flow (DABF), dorsal aortic blood pressure (PDA) and plasma electrolytes were monitored in stanniectomized and sham-operated freshwater eels over a 3-week period; branchial shunting and systemic resistance (RSYS) were estimated. DABF was significantly reduced by 45% from 11.72 +/- 0.48 (control) to 6.55 +/- 0.41 (n = 6; day 21) ml.min-1.kg-1 within 3 weeks after the removal of the corpuscles of Stannius. This large reduction in blood flow was due to a 25% decrease in CO and a 100% increase in estimated branchial shunting which preceded the fall in CO. CO was decreased from 16.07 +/- 0.31 (control) to 11.91 +/- 1 (n = 6; day 21) ml.min-1.kg-1 through a reduction in SV; there was no significant change in HR. Estimated branchial shunting, a relative measure of branchial arterio-venous blood flow, corresponded to 2.53 +/- 0.18 ml.min-1.kg-1 (control; n = 12), which represents 16% of baseline CO. Ventral and dorsal aortic pulse flows also decreased following stanniectomy. The decrease in DABF occurred in conjunction with a reduction in PDA which was measured for 12 days in a separate group of eels. Baseline PDA (3.03 +/- 0.1 kPa) significantly decreased by 15% to 2.55 +/- 0.13 kPa 4 days after stanniectomy. However, this fall in PDA was transient and accompanied by an elevation in derived RSYS. These results support the hypothesis that the corpuscles of Stannius are closely linked to cardiovascular regulation in freshwater eels. Electrolyte changes (hypercalcemia, hypomagnesia, hyperkalemia and hyponatremia) were temporally coupled to the changes in blood flows. Impaired cardiovascular function and altered patterns of blood flow to osmoregulatory organs such as the gills, kidney and skin may have led to some or all of the electrolyte disturbances which followed stanniectomy. PMID- 7798027 TI - Divergent regulation of rat adipocyte GLUT1 and GLUT4 glucose transporters by GH. AB - The effect of GH, in vivo, on the glucose transport systems of rat adipocytes has been investigated. Lowering of serum GH levels, by treatment of rats with an antiserum specific for rat GH (anti-rGH), significantly decreased serum levels of both IGF-I and insulin. Treatment with anti-rGH also increased glucose oxidation and the conversion of glucose to lipid by isolated adipocytes. Adipocyte glucose oxidation and lipid synthesis were measured in the presence of a limiting concentration of glucose and therefore reflect changes in glucose transport. Immunoblot analysis of adipocyte subcellular fractions revealed that anti-rGH induced an increase in the amount of the glucose transporters GLUT1 (1.6-fold) and GLUT4 (2.5-fold) present in plasma membranes and a decrease (39%) in the amount of GLUT4 present in low-density microsomal fractions. Lowering of serum GH also increased, by 36%, the amount of GLUT1 present in a total membrane fraction but had no such effect on GLUT4 levels. Replenishment of serum GH, by concurrent administration of ovine GH to rats, prevented all of these effects of anti-rGH. It was concluded that GH in vivo down-regulates the amount of both GLUT1 and GLUT4 present in rat adipocyte plasma membranes. This reflects a decrease in the total cellular levels of GLUT1 and modification of the subcellular distribution of GLUT4 and results in restriction of adipocyte glucose uptake. PMID- 7798026 TI - The reduction of circulating growth hormone and prolactin in streptozocin-induced diabetic male rats is possibly caused by hypothalamic rather than pituitary changes. AB - To gain further information on diabetes-related disorders in the somatotrophic and lactotrophic axes, we undertook a functional, morphometrical and densitometrical study of the arcuate nucleus (AN), median eminence (ME) and anterior pituitary gland of adult male rats one month after streptozocin-induced diabetes (STZ-D). The basal secretory activity of somatotrophs and lactotrophs was tested by the reverse haemolytic plaque assay (RHPA) and plasma GH and prolactin (PRL) levels were determined by RIA. The number of GH-releasing factor (GRF)-labelled axons and the amount of axonal tyrosine hydroxylase (TH) immunoreactivity increased in STZ-D. There were no significant differences in any of the other densitometrical measurements performed on GRF-, somatostatin-, thyrotropin-releasing hormone- and TH-labelled ME axon cross-sections as well as those on tuberoinfundibular-dopaminergic neurones of the AN in STZ-D compared with control rats. Plasma GH and PRL levels and measurements on anterior pituitary GH- and PRL-labelled structures were decreased in STZ-D. However, the GH and PRL plaque areas were increased after RHPA implying that the secretory capacity of somatotrophs and lactotrophs was not impaired. Taken together, these results suggest that the accumulated GRF in the ME is due to reduced GRF release. This could account for the reduced amplitude and/or frequency of GH secretory pulses. The increased axonal TH-immunoreactivity may indicate an increased dopamine synthesis. If coupled to increased release this could, in turn, be partly responsible for the reduced plasma and anterior pituitary PRL concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798028 TI - Expression of mRNA and immunocytochemical localization of inhibin alpha- and inhibin beta A-subunits in the fetal sheep testis. AB - In order to investigate the ontogeny of gonadal inhibin production in the male fetal sheep, testes were collected from male fetuses at days 70, 100, 130 and 140 of gestation (term = 145 days). The expression and localization of inhibin alpha- and inhibin beta A-subunit mRNA and protein were evaluated using in situ hybridization and immunocytochemistry. The expression of inhibin alpha-subunit mRNA was localized within the seminiferous cords of the developing fetal testis and progressively increased with gestational age. Immunostaining corresponding to immunoreactive inhibin alpha-subunit was detected in Sertoli cells within the seminiferous cords at days 100, 130 and 140 of gestation. In addition, immunostaining was detectable in a small proportion of Leydig cells. No expression of inhibin beta A-subunit mRNA or immunoreactivity was detected in any testicular tissue at any stage of gestation. These data show that the Sertoli cells of the developing fetal sheep testis have the capacity to produce inhibin alpha-subunit by day 100 of gestation and that production increases during late gestation. PMID- 7798029 TI - Regulation of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland. AB - TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (< EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine alpha amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798030 TI - Effect of systemic glucagon administration on ACTH secretion in anaesthetized rats. AB - The effect of glucagon on ACTH secretion was studied in anaesthetized rats injected with either saline (0.1 ml i.m.) or glucagon (0.02 mg/kg i.m.). For the first 90 min after glucagon injection, plasma ACTH fell by 50% from the basal value of 23 +/- 4 pmol/l (mean +/- S.E.M.) to 11 +/- 2 (P = 0.011), after which an abrupt return to baseline occurred (120 min value: 26 +/- 2 pmol/l). In saline injected rats, the baseline ACTH value was not significantly different from either the 90 min value or the 120 min value (27 +/- 3 vs 21 +/- 4 and 24 +/- 3 pmol/l respectively; P > 0.10). Plasma glucose after glucagon peaked at 11.6 +/- 1.1 mmol/l by 15 min but subsequently fell rapidly, attaining the baseline by 60 min. Insulin levels increased sharply after glucagon, from 381 +/- 78 pmol/l to 3172 +/- 668 pmol/l at 15 min, and plateaued at approximately 1000 pmol/l thereafter. No changes in glucose or insulin were seen in saline injected rats. The magnitude of suppression of ACTH after glucagon was not affected either by sustained hyperinsulinaemia (congruent to 1400 pmol/l), induced with continuous glucose infusion to maintain plasma glucose > 12 mmol/l, or by pretreatment with the long-acting somatostatin analogue octreotide (50 micrograms/kg s.c.). However, the return to baseline between 100 and 120 min was prevented both by hyperinsulinaemia induced with sustained hyperglycaemia, and by octreotide. It is postulated that glucagon may inhibit ACTH secretion either by a direct effect on the hypothalamus or indirectly through insulin, which is known to stimulate endogenous somatostatin release. PMID- 7798031 TI - Inhibitory and stimulatory effect of oestrogens upon ovarian 17 alpha hydroxylase/C17,20-lyase in immature hypophysectomized rats treated with gonadotrophin. AB - A study was designed to compare the effects of exogenous and endogenous oestrogens upon the expression of steroid 17 alpha-hydroxylase/C17,20-lyase (CYP17) in the immature hypophysectomized rat ovary. C17,20-lyase activity was measured ex vivo using [21-14C]progesterone, while serum concentrations of androstenedione indicated in vivo activity. Immunocytochemistry was used to localize the enzyme within the ovary. Activity of CYP17 increased dramatically and remained high in thecal and interstitial cells after injection of equine chorionic gonadotrophin, even though serum oestradiol (OE2) levels exceeded 2 nmol/l. Production of comparable serum levels by the use of Silastic capsules containing OE2 greatly suppressed but did not stop, expression of the enzyme induced by repeated doses of human chorionic gonadotrophin (hCG). Subcutaneous implantation of Silastic capsules (1 cm) containing diethylstilboestrol (DES) stimulated follicular growth and increased ovarian weight by 67%, 5 days later. Injection of 50 IU hCG at various times after removal of the implant produced time-dependent changes in CYP17 activity and serum androstenedione levels, when measured 30 h later. Although the initial effect of removal of DES was an increase in CYP17 activity, delaying injection of hCG resulted in a reduced response. The results indicated that: (1) endogenous oestrogens do not inhibit CYP17 expression; (2) exogenous oestrogens only reduce the number of thecal/interstitial cells expressing CYP17 when they are exposed to hCG; (3) pretreatment with oestrogen removes the ovarian interstitial but not the thecal cell expression of CYP17 in response to hCG; and (4) oestrogens can be stimulatory for CYP17 expression in thecal cells. PMID- 7798032 TI - Effect of gonadectomy on growth and GH responsiveness in dwarf rats. AB - Normal rats are sexually dimorphic in their growth and GH secretion. Gonadectomy (Gnx) changes the GH secretory pattern and this could explain differential growth rates in male and female rats. Gonadal steroids may also affect tissue growth directly, or by changing their responsiveness to GH. The effects of Gnx on growth, GH responsiveness, and hepatic GH receptors have now been studied in young (4-7 weeks old) GH-deficient dwarf rats in which the effects of steroid induced alterations in residual endogenous GH secretion will be much less pronounced. Groups of intact and Gnx dwarf rats (n = 5-7) were infused with recombinant human GH (144 micrograms/day) either continuously or in a pulsatile pattern (every 3 h) for 7 days, whilst control groups received saline infusions. Gains in weight, length and tibial bone growth were measured. Female dwarf rats grew significantly more slowly than male dwarfs. Gnx in male dwarfs inhibited growth significantly, whereas ovariectomy had a lesser stimulatory effect in females. Hepatic lactogenic and somatogenic receptors were higher in females and ovariectomy lowered their values towards male levels. Pulsatile GH infusions were more effective than continuous infusions of the same daily GH dose, but when the different underlying growth rates (measured in saline-infused Gnx animals) were taken into account, the responsiveness to pulses of hGH was not different between males and females or between intact and Gnx animals. We have concluded that Gnx in dwarf rats does affect growth, but the effects are small in comparison with those seen in normal rats. Since pulsatile GH infusions stimulated growth more effectively than continuous GH, irrespective of the gonadal steroid status, and the responsiveness to exogenous GH was not changed by Gnx, the results imply that changes in the GH secretory pattern induced by gonadal steroids may have a larger impact on the growth rate than direct effects at the tissue level, at least in the rat. PMID- 7798033 TI - Mechanism of phospholipase D activation induced by extracellular ATP in osteoblast-like cells. AB - We have previously reported that extracellular ATP stimulates Ca2+ influx from extracellular space, resulting in the production of prostaglandin E2 which mediates, at least in part, its proliferative effect on osteoblast-like MC3T3-E1 cells, and that the activation of protein kinase C (PKC) stimulates phospholipase D in these cells. In the present study, we examined the effect of extracellular ATP on phosphatidylcholine-hydrolysing phospholipase D activity in MC3T3-E1 cells. ATP stimulated the formation of both choline and inositol phosphates dose dependently in the range between 0.1 and 1 mM. The formation of choline by a combination of ATP and NaF, an activator of GTP-binding protein, was synergistic, whereas that of inositol phosphates was not. A combination of ATP and 12-O tetradecanoylphorbol-13-acetate, a PKC activating phorbol ester, additively stimulated the formation of choline. Staurosporine, an inhibitor of PKC, had little effect on ATP-stimulated formation of choline. Choline formation was significantly reduced by chelating extracellular Ca2+ with EGTA, while being inhibited by W-7, an antagonist of calmodulin. These results suggest that extracellular ATP stimulates phospholipase D in a Ca2+/calmodulin-dependent manner in osteoblast-like cells, and that neither PKC activation nor GTP-binding protein is involved in this mechanism. PMID- 7798034 TI - Ovine placental lactogen lacks direct somatogenic and anticatabolic actions in the postnatal lamb. AB - The metabolic effects of ovine placental lactogen (oPL) alone and in combination with bovine GH (bGH) were investigated in comparison with the identical dose of bGH alone in the well-fed postnatal lamb. The animals were treated by twice daily intramuscular injection for 5 days with oPL (n = 7), bGH (n = 7) or bGH+oPL (n = 7) at a dose of 0.3 mg/kg per day or saline (n = 9). bGH and bGH+oPL treatments, but not oPL treatment, resulted in significantly (P < 0.01) higher plasma IGF-I levels than saline treatment. The rate of net protein catabolism (NPC) was significantly (P < 0.05) reduced to the same extent by bGH and bGH+oPL treatment compared with saline treatment. In contrast, oPL did not affect the rate of NPC. Blood glucose and insulin:glucose ratio were significantly (P < 0.05) elevated in the bGH+oPL group, whereas they were not significantly altered by either bGH or oPL treatment. These results suggest that oPL alone is not somatogenic or anticatabolic in the postnatal lamb despite the earlier evidence that oPL can bind to the oGH receptor (oGHR). However, oPL appeared to augment some of the effects of bGH when administered together, particularly with respect to carbohydrate metabolism. Potentiation of the diabetogenic effect of bGH by oPL may lead to insulin resistance during pregnancy. The lack of any obvious actions by oPL treatment alone may support the hypothesis that oGHR homo-dimerization is required for the full activation of GHR-mediated effects, since oPL binding does not initiate homo-dimerization of the oGHR. PMID- 7798035 TI - Oxytocin antagonists delay the initiation of parturition and prolong its active phase in rats. AB - The physiological importance of oxytocin for the initiation and maintenance of labour and delivery is controversial. We investigated the effects of two novel peptide oxytocin antagonists on the onset and the progress of delivery in rats implanted with a jugular vein cannula one day before term. During delivery rats were given either an oxytocin antagonist (OVT16, n = 10, or F382, n = 7, 30 micrograms/kg) or vehicle (n = 10, 9) after the birth of the second pup and the time to deliver five more pups was recorded. Other rats were given an injection of F382 (30 micrograms/kg, n = 7) or vehicle (n = 9) after the birth of the fourth pup and the time to deliver three more pups was recorded. In another experiment rats were given repeated injections of F382 (30 or 60 micrograms/kg, n = 13, 11) or vehicle (n = 32) prepartum on the day of expected term and the time of onset and the progress of delivery was recorded. Rats given an antagonist after the second pup delivered the next five pups in 100 +/- 8 min (F382) and 83 +/- 12 min (OVT16), significantly slower than the respective controls (51 +/- 6 and 49 +/- 6 min, U-test, P < 0.05). Four of the 7 rats given F382 after the fourth pup showed no prolongation of delivery (time between pups 4-7: 24.7 +/- 2.9 vs 27.5 +/- 3.1 min in controls), while in the other three rats delivery was prolonged (time between pups 4-7: 86 +/- 4.3 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798036 TI - Public health medicine and primary health care: convergent, divergent, or parallel paths? PMID- 7798037 TI - International variation in socioeconomic inequalities in self reported health. AB - STUDY OBJECTIVE: To assess the extent to which the size of socioeconomic inequalities in self reported health varies among industrialised countries. DESIGN: Cross sectional data on the association between educational level and several health indicators were obtained from national health interview surveys. This association was quantified by means of an inequality index based on logistic regression analysis. SETTING: The national, non-institutionalised populations of the United Kingdom, Sweden, Denmark, Germany, The Netherlands, Italy, the United States, and Canada were studied. The age group was 15-64 years, and the study period was 1983-90. PARTICIPANTS: Representative population samples with the number of respondents ranging from approximately 6000 (Denmark) to 90,000 (the United States) were studied. MAIN RESULTS: For men, the smallest health inequalities were observed for the United Kingdom and Sweden, and the largest inequalities for Italy and the United States. Other countries held an intermediate position. The same international pattern was observed for women, except that relatively small inequalities were also observed for Dutch women. CONCLUSIONS: The results agree to a large extent with those of previous comparative studies. The international pattern observed here may be partly related to "subjective" aspects of self reported health, such as the propensity to complain and illness behaviour. The results challenge the view that disease and disability are distributed less equally in the UK than in countries like Sweden. PMID- 7798038 TI - Sickness absence as a measure of health status and functioning: from the UK Whitehall II study. AB - STUDY OBJECTIVE: To investigate the relationship between self reported health status and sickness absence. DESIGN: Analysis of questionnaire and sickness absence data from the first phase of the Whitehall II study--a longitudinal study set up to investigate the degree and causes of the social gradient in morbidity and mortality. SETTING: London offices of 20 civil service departments. PARTICIPANTS: Altogether 6895 male and 3413 female civil servants aged 35-55 years. Analysis was conducted on 88% of participants who had complete data for the present analysis. MAIN RESULTS: A strong inverse relation between the grade of employment (measure of socioeconomic status) and sickness absence was observed. Men in the lowest grade had rates of sickness absence six times higher than those in the highest grade. For women the corresponding differences were two to five times higher. In general, the longer the duration of absence, the more strongly did baseline health predict rates of absence. However, the health measures also predicted shorter spells, although to a lesser extent. Job satisfaction was strongly related to sickness absence with higher rates in those who reported low job satisfaction. After adjusting for health status the association remained for one to two day absences, but was greatly reduced for absences longer than three days. CONCLUSION: There was a strong association between ill health and sickness absence, particularly for longer spells. The magnitude of the association may have been underestimated because of the strength of the association between grade of employment and sickness absence. It is proposed that sickness absence be used as an integrated measure of physical, psychological, and social functioning in studies of working populations. PMID- 7798039 TI - Health status: does it predict choice in further education? AB - STUDY OBJECTIVE: To study the significance of a young person's health to his or her choice of further education at age 16. DESIGN: A cross sectional population survey SETTING: The whole of Finland. PARTICIPANTS: A representative sample of 2977 Finnish 16 year olds. The response rate was 83%. MEASUREMENTS AND MAIN RESULTS: The three outcome variables reflected successive steps on the way to educational success: school attendance after the completion of compulsory schooling, the type of school, and school achievement for those at school. Continuing their education and choosing upper secondary school were most typical of young people from upper social classes. Female gender and living with both parents increased the probability of choosing to go on to upper secondary school. Over and above these background variables, some health factors had additional explanatory power. Continuing their education, attending upper secondary schools, and good achievement were typical of those who considered their health to be good. Chronically ill adolescents were more likely to continue their education than the healthy ones. CONCLUSIONS: School imposes great demands on young people, thus revealing differences in personal health resources. Adaptation to the norms of a society in which education is highly valued is related to satisfying health status. In a welfare state that offers equal educational opportunities for everyone, however, chronically ill adolescents can add to their resources for coping through schooling. Health related selection thus works differently for various indicators of health and in various kinds of societies. Social class differences in health in the future may be more dependent on personally experienced health problems than on medically diagnosed diseases. PMID- 7798040 TI - Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study. AB - STUDY OBJECTIVE: To explore the relationship between self reported environmental tobacco smoke exposure (or passive smoking), the serum cotinine concentration, and evidence of respiratory or coronary disease in men and women who have never smoked. DESIGN: Cross sectional random population survey identifying disease markers and relating them to measures of passive smoking. Disease markers were previous medical diagnoses, response to standard symptom questionnaires, and electrocardiographic signs. SETTING: Samples of men and women aged 40-59 years drawn from general practitioner lists in 22 local government districts of Scotland, between 1984 and 1986. PARTICIPANTS: A total of 786 men and 1492 women who reported never having smoked tobacco, and who had serum cotinine concentrations below 17.5 ng/ml, the cut off point for smoking "deceivers", took part. RESULTS: Fewer than one third of never smokers reported no recent exposure to environmental tobacco smoke and the same proportion had no detectable cotinine. Women had lower cotinine values than men but reported more exposure to smoke. The correlation between the measures of exposure was poor. Self-reported exposure showed strong, statistically significant, dose response relationships with respiratory symptoms and with the coronary disease markers. These relationships were weak or absent for serum cotinine, except for diagnosed coronary heart disease. Here the dose response gradient was as strong as that for self report, with an odds ratio of 2.7 (95% CI 1.3, 5.6) for the highest v the lowest exposure group, adjusted for age, housing tenure, total cholesterol, and blood pressure, and not explained by fibrinogen. CONCLUSIONS: The validity of different measures of tobacco smoke exposure needs further investigation. The gradient of diagnosed coronary heart disease with both self reported exposure and serum cotinine was, however, surprisingly strong, statistically significant, and unexplained by other factors. These findings reinforce current policies to limit passive tobacco smoke exposure. PMID- 7798041 TI - Coronary risk factor levels: differences between educational groups in 1972-87 in eastern Finland. AB - STUDY OBJECTIVE: To compare differences in coronary heart disease (CHD) risk factor levels between educational groups in the 1970s and 1980s in eastern Finland. DESIGN AND PARTICIPANTS: Independent, cross sectional population surveys were undertaken in 1972, 1977, 1982, and 1987 of randomly selected men and women aged 30-59 living in two provinces in eastern Finland. Altogether 20,096 subjects participated. The lowest observed level of participation in either sex or province in any year was 77%. Serum cholesterol values and blood pressure measurements, body mass index, smoking, and the level of education were determined in each survey using comparable methodology. MAIN RESULTS: More poorly educated men and women had higher levels of all risk factors at the end of the study period (1987). There was no change between 1972 and 1987 in differences between educational groups in mean serum cholesterol values and the diastolic blood pressure level in either sex, and in smoking in men. In women, the proportion of smokers was highest in the better educated in the 1970s but lowest in this group in the 1980s (interaction between year of examination and educational level p < 0.01). Differences between educational groups in mean body mass index increased with time in both men (p < 0.001) and women (p = 0.06). CONCLUSIONS: Relative differences between socioeconomic groups in CHD mortality have increased in Finland in the 1970s and 1980s. Present results from eastern Finland show no reduction in differences between educational groups in risk factor levels, and even some evidence of increasing differences. Although a comparison between mortality trends and risk factor trends is problematic, trends in the risk factors analysed do not seem to be a major cause for the increasing differences in CHD mortality in Finland, at least in men. On the other hand, the risk factor trends analysed show no progress towards reducing inequalities in health, a major goal of public health policy. PMID- 7798042 TI - Establishing baseline data in cancer registration in northern England: implications for Health of the Nation targets. AB - OBJECTIVE: To assess the completeness and accuracy of cancer surveillance data relevant to Health of the Nation targets. DESIGN: A comparison of locally ascertained data on cancer with recorded cancer registry sources in selected diagnoses. SETTING: The district of South West Durham within the Northern Regional Health Authority. PATIENTS: All patients with lung, skin, and malignant cervical cancer who were resident and diagnosed in the district or identified in the Northern Region Cancer Registry during the calendar period 1989-91. MAIN RESULTS: Of 544 cases of cancer identified from all available sources, 448 (95.8%) were registered, ranging from 93.9% for malignant cervical cancer to 96.7% for skin cancer. In 448 cases which were both identified locally and registered, 53 (11.8%) showed disagreements between local sources and register data, involving classification of site and timing of registration. Twenty three cases were identified locally but were not registered, 22 registered but not identified locally, and 51 registered with the casenotes missing locally. CONCLUSIONS: Any real achievement of Health of the Nation targets may be masked by changes over time in the accuracy and completeness of information systems. In assessing the achievement or otherwise of targets, it is important to be aware of any differences in the completeness and accuracy of the baseline data compared to future measurements. PMID- 7798043 TI - Cervical cancer: incidence and survival in migrants within Spain. AB - STUDY OBJECTIVE: This study examined the incidence of cervical cancer and survival rates according to migrant experience of women from different regions of Spain to Girona, Catalonia (Spain). DESIGN: Using data from the population based cancer registry of Girona for the period 1980-89, crude and age adjusted incidence rates were calculated for local-born and first generation migrants from other Spanish regions. The age standardised rate ratio (SRR) was calculated and Cox's regression model was used to adjust survival according to migrant status for age and stage at diagnosis. MAIN RESULTS: The incidence of cervical cancer was significantly higher in first generation Spanish migrants compared with locally born women (SRR: 2.02; 95% CI 1.40:2.92). The stage at diagnosis was more advanced among migrants. Survival probability was significantly associated with stage at diagnosis, but age and region of birth were not. CONCLUSIONS: Migrants from the southern Spanish regions show a twofold excess in the incidence of cervical cancer compared with the Girona-born female population. Cases of cervical cancer in migrants are diagnosed at a more advanced stage and as a consequence have a poorer prognosis. PMID- 7798044 TI - Childhood cancers: space-time distribution in Britain. AB - STUDY OBJECTIVES: To examine a national data set of all childhood cancers for evidence of space-time interactions within three distinct sets of dates and places (at birth, at diagnosis, and at death), to show whether the patterns found for these events represent separate phenomena or statistically interdependent processes, and to see whether the childhood leukaemias and the childhood solid cancers have separate distinctive patterns in these respects. DESIGN: This was a space-time cluster analysis. The large number of cases enabled division of the data into two sets, one for hypothesis generation and the other for hypothesis testing. SETTING: England, Scotland, and Wales. SUBJECTS: A national collection of 22,360 children aged 0-15 years with fatal cancers and leukaemias in the period 1953 to 1980. MAIN RESULTS: There was significant clustering among the leukaemias and lymphomas on date and place of birth (particularly among cases born within 1 km and up to 5 months apart), and on date and place of diagnosis (particularly among cases diagnosed from 3 to 5 km apart and up to 9 months apart). There was no clustering among the solid cancers. These findings were confirmed in two separate analyses of two separate sets of data. CONCLUSIONS: The birth clustering was significant among pairs diagnosed at differing ages, and diagnosis clustering was significant among pairs born at different times, and it was concluded that the two types of clustering must be regarded as separate and statistically independent phenomena. Both the birth and the diagnosis clusters comprised many independent pairs of cases, with no large multiple case clusters. This suggests the involvement of multiple time-space localised exposures to hazards with short and constant latent intervals; probably an infectious agent or an environmental toxin. Given the separate nature of the two types of clustering, exposure to more than one hazard may be involved. PMID- 7798045 TI - Down's syndrome: prevalence and ionising radiation in an area of north west England 1957-91. AB - OBJECTIVE: To analyse the prevalence of Down's syndrome in a specific, geographical area and seek to explain variations with particular reference to ionising radiation. DESIGN: Cases were ascertained by one paediatrician as part of a prospective survey of major congenital malformations in children born to residents of an area of Lancashire between 1957 and 1991. Temporal changes in prevalence rates were detected by a grid search technique using Poisson log linear models. These models were also used to determine the association between prevalence and ionising radiation from atomic fall out. SETTING: The Fylde district of Lancashire in the north west of England. PATIENTS: There were 167 cases, including five stillbirths and eight terminations, among 124,015 total births in a population which increased from about 250,000 to over 300,000 during the study period. MAIN RESULTS: There was significant increase in the prevalence of all cases conceived in 1963 and 1964, and a lesser peak in 1958 which did not quite reach statistical significance. There was no evidence that the increased prevalence in 1963-64 was a result of changes in the maternal age distribution in the population. Babies of mothers aged 35 years and over accounted for more of the variation, especially in 1958 when their increase was significant. There was a highly significant association between prevalence and radiation from fallout produced by atmospheric testing of atomic weapons. The 1963-64 peak coincided with the maximum estimated radiation dose. The lesser peak in 1958 also coincided with increased exposure to radiation from fallout, possibly enhanced by ground deposits after a fire at the Windscale reactor in October 1957. CONCLUSION: This study provides further support for low dose ionising radiation as one aetiological factor in Down's syndrome. PMID- 7798046 TI - Birth prevalence of malformations in members of different ethnic groups and in the offspring of matings between them, in Birmingham, England. AB - STUDY OBJECTIVES: The aims were: (1) to compare the birth prevalence of malformations in different ethnic groups and (2) to explore the reasons for the ethnic variations found by examining birth prevalence in the offspring of matings between ethnic groups. DESIGN: Analysis of data from a register of malformations and register of births. SETTING: Birmingham, England. SUBJECTS: A total of 432,778 infants (including stillbirths) born in 1960-84. MAIN RESULTS: Significant differences (p < 0.01) between ethnic groups were exhibited by the birth prevalence of neural tube defects (NTD), cleft palate, cleft lip, oesophageal atresia/fistula, hypospadias, hip dislocation, clubfoot, polydactyly, and syndactyly. In the offspring of matings between parents of European and Caribbean origin, the birth prevalence of NTD, cleft lip, hypospadias, hip dislocation, polydactyly, and syndactyly seemed more likely to be influenced by the ethnicity of both parents than by that of the mother alone. The reverse was true for the birth prevalence of NTD in subjects with one parent of Irish origin and on of British. CONCLUSIONS: Genetic differences may be responsible for Europeans being at lower risk of polydactyly and at higher risk of NTD, cleft lip, hypospadias, hip dislocation, and syndactyly than Caribbeans. Variations in the intrauterine environment are more likely to account for NTD being more common in Irish than in British subjects. PMID- 7798047 TI - Physical fitness of 9 year olds in England: related factors. AB - STUDY OBJECTIVE: To examine the influence of social factors, passive smoking, and other parental health related factors, as well as anthropometric and other measurements on children's cardiorespiratory fitness. DESIGN: This was a cross sectional study. SETTING: The analysis was based on 22 health areas in England. PARTICIPANTS: The subjects were 299 boys and 282 girls aged 8 to 9 years. Parents did not give positive consent for 15% of the eligible sample. A further 25% of the eligible sample did not participate because the cycle-ergometer broke down, study time was insufficient, or they were excluded from the analysis because they were from ethnic minority groups or had missing data on one continuous variable. MEASUREMENTS AND MAIN RESULTS: Cardiorespiratory fitness was determined using the cycle-ergometer test. It was measured in terms of PWC85%-that is, power output per body weight (watt/kg) assessed at 85% of maximum heart rate. The association between children's fitness and biological and social factors was analysed in two stages. Firstly, multiple logistic analysis was used to examine the factors associated with the children's ability to complete the test for at least four minutes. Secondly, multiple linear regression analysis was used to examine the independent association of the factors with PWC85%. In the logistic analysis, shorter children, children with higher blood pressure, and boys with a larger sibship size had poorer fitness. In the multiple regression analysis, only height (p < 0.001) was positively associated, and the sum of skinfold thicknesses at four sites (p = 0.001) was negatively associated with fitness in both sexes. In girls, a positive association was found with pre-exercise peak expiratory flow rate (p < 0.05), and there were negative associations with systolic blood pressure (p < 0.05) and family history of heart attack (p < 0.05). In boys an association was found with skinfold distribution and fitness (p < 0.05), so that children with relatively less body fat were fitter. Social and health behaviour factors such as father's social class, father's employment status, or parents' smoking habits were unrelated to child's fitness. CONCLUSION: Height and obesity are strongly associated, and systolic blood pressure to a small extent, with children's fitness, but social factors are unrelated. PMID- 7798050 TI - The hospital admissions study in England: are there alternatives to emergency hospital admission? AB - STUDY OBJECTIVE: To assess the potential for substituting alternative forms of care for admission to an acute hospital in particular groups of patients. DESIGN: A screening tool, the intensity-severity-discharge review system with adult criteria (ISD-A), developed for hospital utilisation review in the USA, was used in a cohort of hospital admissions to identify a group of patients who could potentially have been treated outside the acute hospital. These patients were further assessed by a panel of general practitioners (GPs) to determine the most appropriate alternative form of care. A cost analysis was performed on the results obtained. SETTING: General medicine and geriatric specialties in one acute hospital in the south western region. PATIENTS: Patients comprised a sample of 701 admitted to general medical and geriatric specialties. MAIN RESULTS: The screening tool identified 19.7% of admissions for whom there was potential for treatment outside the acute hospital. Assessment by the GP panel reduced this potential to between 9.8% and 15.0% of emergency admissions. The alternatives most frequently identified as "most appropriate" were the community hospital/GP bed and the urgent outpatient assessment (within either 24 or 48 hours). Potential resource savings based on the average cost were relatively small. This potential seemed to be greater for the alternative of the urgent outpatient assessment. CONCLUSIONS: Potential exists for treating a proportion of patients in lower intensity alternatives to the acute hospital. If this potential were exploited few resource savings would occur. PMID- 7798049 TI - Risk factors for childhood burns: a case-control study of Ghanaian children. AB - STUDY OBJECTIVE: To study risk factors for childhood burns in order to identify possible preventive strategies. DESIGN: Case-control design with pair matching of controls to cases in relation to age, sex, and area of residence. The cases and controls were identified by a community based, multisite survey. The effects of host and socioenvironmental variables reported by mothers were investigated in a multivariate analysis using conditional logistic regression. SETTING: A developing country setting the Ashanti Region in Ghana. PARTICIPANTS: These comprised 610 cases aged 0-5 years who had been burned (as evidenced by a visible scar) and 610 controls with no burn history. MAIN RESULTS: The presence of a pre existing impairment in a child was the strongest risk factor in this population (OR = 6.71; 95% CI 2.78, 16.16). Other significant risk factor included: sibling death from a burn (OR = 4.41; 95% CI 1.16, 16.68); history of burn in a sibling (OR = 1.79; 95% CI 1.24, 2.58); and storage of a flammable substance in the home (OR = 1.51; 95% CI 1.03; 2.21). Maternal education had a protective effect against childhood burns, although this effect was not strong (OR = 0.76; 95% CI 0.55, 1.05). CONCLUSIONS: Community programmes to ensure adequate child supervision and general child wellbeing, particularly for those with impairments, as well as parental education about burns are recommended, to reduce childhood burns in this region of Ghana. The public should bed advised against storing flammable substances in the home. PMID- 7798048 TI - Child pedestrian deaths: sensitivity to traffic volume--evidence from the USA. AB - STUDY OBJECTIVE: In case centred epidemiological studies, traffic volume has been shown to be a potent risk factor for child pedestrian injuries. Nevertheless, over the past two decades child pedestrian death rates have fallen in many countries despite large increases in traffic volumes, suggesting that other factors are responsible for the long term decline in death rates. This study aimed to investigate the relationship between short term changes in traffic volume and child pedestrian death rates. DESIGN: The relationship between child pedestrian death rates and traffic volume in the USA for the period 1970-88 was investigated. Trends in death rates and in traffic volume were removed by the time series method of differencing. RESULTS: After removing the long term trends, there was a close relationship between the year to year variation in traffic volume and the year to year variation in the child pedestrian death rate. Most notably, in the two periods when traffic volume actually fell, the falls in the child pedestrian death rate were considerably larger than those seen at any other time. Overall, decelerations in the rate of increase in traffic volume were accompanied by accelerations in the rate of decline in the child pedestrian death rate. CONCLUSION: While other factors may determine long term trends in child pedestrian death rates, they are very sensitive to short term changes in traffic volume. Public policy changes which limit the growth in traffic volume have the potential to accelerate the decline in child pedestrian death rates. PMID- 7798052 TI - Estimating the sexual mixing patterns in the general population from those in people acquiring gonorrhoea infection: theoretical foundation and empirical findings. AB - STUDY OBJECTIVES: To describe mathematically the relationship between patterns of sexual mixing in the general population and those of people with gonorrhoea infection, and hence to estimate the sexual mixing matrix for the general population. DESIGN: Integration of data describing sexual behaviour in the general population, with data describing sexual behaviour and mixing among individuals infected with gonorrhoea. Use of these data in a simple mathematical model of the transmission dynamics of gonorrhoea infection. SETTING: The general population of London and a genitourinary medicine (GUM) clinic in west London. PARTICIPANT: These comprised 1520 men and women living in London who were randomly selected for the national survey of sexual attitudes and lifestyles and 2414 heterosexual men and women who presented to the GUM clinic with gonorrhoea. MAIN RESULTS: The relationship between sexual mixing among people with gonorrhoea and sexual mixing in the general population is derived mathematically. An empirical estimate of the sexual mixing matrix for the general population is presented. The results provide tentative evidence that individuals with high rates of acquisition of sexual partners preferentially select other individuals with high rates as partners (assortative mixing). CONCLUSIONS: Reliable estimates of sexual mixing have been shown to be important for understanding the evolution of the epidemics of HIV infection and other sexually transmitted diseases. The possibility of estimating patterns of sexual mixing in the general population from information routinely collected in gonorrhoea contact tracing programmes is demonstrated. Furthermore, the approach we describe could, in principle, be used to estimate the same patterns of mixing, using contact tracing data for other sexually transmitted diseases, thus providing a way of validating our results. PMID- 7798051 TI - Assessing equity in access to health care provision in the UK: does where you live affect your chances of getting a coronary artery bypass graft? AB - STUDY OBJECTIVES: Equity should be monitored routinely for all health care services, but ideal studies for each service would be prohibitively expensive and time consuming. A simple, quick, and cheap method for the preliminary exploration of equity in health care provision using routine data was devised. This method was illustrated by examining whether coronary artery bypass graft (CABG) operations reflect socioeconomic differences in ischaemic heart disease (IHD) mortality. DESIGN: Ecological comparison of operation rates was undertaken for CABG for 1991 and IHD mortality for 1981-85 by quartiles of Townsend deprivation score. SETTING: North East Thames Regional Health Authority, London, UK. SUBJECTS: All residents of this region aged 35-74 were the denominator population. Numerators were 26,834 IHD deaths and 1041 CABG operations for the defined time periods. MAIN RESULTS: IHD mortality showed a steady, significant increase with increasing area deprivation scores for both men and women. CABG rate ratios increased linearly for women, while for men there was a U shaped pattern, being lowest for the second and third quartiles. This pattern was attenuated, but not abolished, when adjusted for geographical proximity to cardiothoracic surgical units. The ratio of CABG operations to IHD mortality by deprivation was relatively constant in women suggesting equitable provision. In men, this ratio was significantly lower for the third quartile. CONCLUSIONS: Inequities may exist in the provision of CABG operations for men in this region and this finding should be the stimulus for further detailed studies. Other health care systems should also examine equity in provision. PMID- 7798054 TI - Growth and relative stability of the proportion permanently sick in English family health service authorities, 1981-91. PMID- 7798053 TI - Components of small area variation in death rates: a method applied to data from Sweden. AB - STUDY OBJECTIVES: The study aimed to develop and evaluate a method for small area analysis of different non-random components of the variation in death rates. The method was applied to incidence and mortality data for selected malignant neoplasms in 26 administrative health areas in Sweden. DESIGN: Variation in mortality and incidence rates for malignant neoplasms of the trachea, bronchus, and lung; colon; rectum; and cervix uteri in the 26 health areas were analysed after standardisation for age. In addition, the systematic and random components of variance were estimated. The systematic component of variance in mortality was divided into two additive components-one component was dependent on the variation in the corresponding incidence rates and the other remained after adjustment for incidence. SETTING AND PARTICIPANT: All cases diagnosed between 1972 and 1983 and all deaths between 1974 and 1985 for selected malignant neoplasms in Swedish citizens and other residents in Sweden, aged between 0 and 64 years, were analysed. MAIN RESULTS: Much of the observed variation in mortality was explained by the estimated random variation. For malignant neoplasms of the trachea, bronchus, and lung the systematic variation in mortality was mainly explained by the variation in incidence. For cancer of the cervix uteri, alone, there was significant systematic variation of moderate magnitude that was not explained by the incidence rates. CONCLUSIONS: These methods made it possible to divide the observed variance in mortality into different components. Random effects and variance in incidence rates were found to be of great importance when analysing the variance in death rates between health areas. By studying different systematic components of variation it is possible to identify fields for in depth studies on the quality of prevention and treatment. PMID- 7798055 TI - Aetiology of peptic ulcer in Norway. PMID- 7798056 TI - Pap smear compliance among norplant users. PMID- 7798058 TI - Vaginal smears after hysterectomy. PMID- 7798057 TI - Vaginal smears after hysterectomy. PMID- 7798059 TI - Telemedicine. PMID- 7798060 TI - Structure and financing of health care. PMID- 7798062 TI - A common basis for general practice/family medicine in Europe. PMID- 7798061 TI - Pearls from geriatrics, or a long line at the bathroom. PMID- 7798063 TI - Physicians and organizations: an uneasy alliance or a welcome relief? AB - BACKGROUND: Physicians are increasingly practicing within structured or organized practice settings, even though it is frequently assumed that such organizations are inherently dissatisfying to physicians. In this study, a sensitive measure of physician satisfaction is used to compare physicians working in four types of practice settings: private group practice, solo practice, a closed-panel health maintenance organization (HMO), and a hospital-based practice. METHODS: A questionnaire was mailed to all physicians in a four county area in western Massachusetts, from which 1302 practicing physicians were identified. Based on responses to the questionnaire, the physicians were placed into one of the four practice arrangements. Satisfaction was measured by using an index methodology, with six statistically acceptable measures of satisfaction. RESULTS: All physicians surveyed were most satisfied with the personal and lifestyle factors related to their practice, regardless of practice setting. Those in a private group practice were the most satisfied. However, physicians in an HMO setting were more satisfied with medicine as a profession and less dissatisfied with the state's medical practice climate than physicians in the other practice settings. It appears that HMOs provide professional satisfaction by buffering physicians from the external regulatory climate, permitting them to focus more on patient care. CONCLUSIONS: Identifying the factors that cause physician satisfaction and dissatisfaction within the various types of practice settings becomes increasingly important as current health care reform efforts continue to promote more structured practice environments. More research is needed to identify the various organizations physicians are involved with so that physicians' professional level of satisfaction can be maximized. PMID- 7798065 TI - Disqualifying criteria in a preparticipation sports evaluation. AB - BACKGROUND: This study was undertaken to demonstrate the relative frequency of disqualifying criteria in a complete history and physical sports examination. METHODS: A review was conducted of 2574 preparticipation physical evaluations (PPEs) performed on 11- to 18-year-old student athletes to determine which factors are associated with denial of unrestricted sports participation. RESULTS: Eighty-five percent of the student athletes passed the screening. Of those who did not, the denial decision was based on the medical history alone in 58% of cases (P < .05). A logistic regression analysis identified seven items associated with denial: dizziness with exercise, history of asthma, body mass index, systolic blood pressure, visual acuity, heart murmur, and musculoskeletal examination. CONCLUSIONS: Although physicians often take a complete history and perform physical examinations, relatively few variables appear related to denial of eligibility for participation in organized sports. The history is one of the most important aspects of the PPE. A directed PPE may be more efficient, thereby allowing more time to address other important issues. PMID- 7798064 TI - Prostate cancer screening: a decision analysis. AB - BACKGROUND: The issue of whether to screen men for prostate cancer is controversial. No randomized clinical trials have been completed to confirm the efficacy of screening for prostate cancer. We created a mathematical model of the clinical risks and benefits of screening for prostate cancer. METHODS: A Markov decision-analytic model evaluated the outcomes of annually screening asymptomatic men for prostate cancer beginning at age 50 years. The screening and testing algorithm included the digital rectal examination, transrectal ultrasound, and prostate-specific antigen test. A sample of 10 male patients with no history of prostate disease were interviewed to assess their utilities (preferences) regarding the various adverse outcomes of prostate cancer treatment. RESULTS: The model indicated that no screening was preferred to screening when patients' utilities were considered (24.14 vs 23.47 quality-adjusted life years expected). The optimal decision was sensitive to the utilities of impotence and urethral stricture, the most common adverse outcomes for patients under the age of 65 years. When adverse outcomes of treatment were ignored, screening was favored (24.86 vs 24.22 years of life expectancy. CONCLUSIONS: When quality-of-life preferences of men are considered, the annual screening of asymptomatic patients for prostate cancer is not recommended. PMID- 7798067 TI - Prevalence of lead poisoning in a suburban practice. AB - BACKGROUND: The purpose of this study was to determine the prevalence of elevated blood lead levels (EBLLS, lead > or = 10 micrograms/dL [0.48 mumol/L]) in a suburban family practice setting and to assess the utility of a questionnaire as an alternative to universal screening in identifying individuals with EBLL in a low-risk population. METHODS: Parents bringing children aged 1 through 3 years into the office for any type of visit were offered the opportunity to complete a questionnaire concerning risk for lead poisoning and to obtain free blood lead testing for their child. No child in this study had previously been tested for lead toxicity. The lead levels found on testing were correlated with the questionnaire results. RESULTS: Two hundred thirty-two children with an average age of 20 months were tested. Blood lead levels ranged from 0 to 53 micrograms/dL (2.56 mumol/L). Elevated blood lead levels were found in 5.6% of the study population. The five questions suggested by the Centers for Disease Control and Prevention (CDC) were taken as a group, and any "yes" or "don't know" response was considered a risk factor. These questions had a sensitivity of 84.6% and a specificity of 41.6% in identifying children with EBLL. An additional question regarding residence in a home built before 1960 (or not knowing the age of the home) was a better screening test for EBLL (sensitivity 92.3%, specificity 57.1%) than the five CDC questions. Lower household income was associated with an EBLL, but sex, race, and home location (urban, suburban, rural) were not. CONCLUSIONS: Risk-assessment questionnaires are useful tools in selecting children who are at risk for an EBLL from low-risk populations. Comparison of this study with similar studies suggests that the most useful questions for this purpose may vary according to location. In this and other studies to date, however, questionnaires show less than 100% sensitivity in identifying children with EBLL. PMID- 7798066 TI - Selection of skin test antigens to evaluate PPD anergy. AB - BACKGROUND: A purified protein derivative (PPD) tuberculin skin test may be nonreactive because of cutaneous anergy, technical problems with the test, or absence of tuberculosis infection. This study investigated the sensitivity and specificity of five test agents in measuring cutaneous anergy when the PPD test is nonreactive. Agents evaluated include antigens for Candida, mumps, histoplasmin, tetanus, and Trichophyton. METHODS: Delayed-type hypersensitivity skin test records were analyzed in 1113 patients admitted to the University of Texas Health Center at Tyler from December 1988 through June 1993. These patients were admitted with initial diagnoses of diseases other than active tuberculosis or human immunodeficiency virus infection. RESULTS: Patients with a negative PPD test reacted most often to the control skin test Candida (63.5%), followed by mumps (52.2%), histoplasmosis (37.2%), tetanus (35.7%), and Trichophyton (6.1%). Analysis of these data indicates that the use of more than three of the four most commonly reactive control tests (Candida, mumps, and histoplasmin or tetanus) yielded minimal additional precision in the determination of skin test anergy compared with using all five control skin tests. This finding remained constant whether the PPD was considered negative at < 5 mm, < 10 mm, or < 15 mm of induration. CONCLUSIONS: In controlling for false-negative PPD tests, the use of three skin test antigens, Candida, mumps, and tetanus, should provide reliable control for delayed-type hypersensitivity anergy. PMID- 7798069 TI - Drug interactions with antibacterial agents. AB - Antibacterial drugs, such as quinolones, macrolides, rifampin, isoniazid, and trimethoprim-sulfamethoxazole, can interact with other drugs in a wide variety of clinically significant ways. They are frequently administered with other prescription and nonprescription medications. Antibacterial agents may interact by causing a change in the pharmacokinetics or pharmacodynamics of a second drug. In other cases, the antimicrobial may be affected by the action of another drug. Interactions involving antimicrobials often result from alterations in the absorption of the antimicrobial from the gastrointestinal tract or changes in the hepatic metabolism or renal elimination of the drugs concurrently administered. While certain classes of antibacterial drugs are known to interact with many other drugs, the interaction potential of most classes of antimicrobials is not uniform among members of the class. This diversity in interaction potential provides the clinician with an opportunity to avoid potential interactions by means of appropriate drug selection. An understanding of the common, clinically significant drug interactions involving antibacterial agents will enable the physician to avoid unnecessary adverse drug reactions. PMID- 7798068 TI - Conversion from 2.5 mg to 1.25 mg indapamide in patients with mild to moderate hypertension. AB - BACKGROUND: Indapamide is an effective antihypertensive drug with diuretic and vasodilating activities. The common starting dose has been 2.5 mg to 5 mg. A lower dose formulation (1.25 mg) is now available. The safety and efficacy of switching patients from indapamide 2.5 mg to indapamide 1.25 mg was evaluated in this randomized, double-blind, multicenter clinical trial. METHODS: Three hundred seventy-eight adult patients with mild to moderate essential hypertension were enrolled in a washout period, during which patients received single-blind placebo for 4 weeks. All 378 patients qualified for the study and received open-label treatment with indapamide 2.5 mg for 8 weeks. Of the 378 patients, 265 responded to indapamide 2.5 mg and were randomized to receive double-blind treatment with either indapamide 1.25 mg (n = 132) or 2.5 mg (n = 133) for 8 weeks. Overall, 245 of the 378 patients who were initially enrolled completed the study. The primary efficacy variable was the number of patients in each treatment group who maintained a supine diastolic blood pressure of < or = 90 mm Hg (treatment success) by the end of the double-blind period (week 16). RESULTS: Treatment with indapamide 1.25 mg once daily was as efficacious as the 2.5-mg once-daily dose. No significant difference was observed for the percentage of patients who achieved treatment success between the patients switched from indapamide 2.5 to 1.25 mg (74%) and the control group maintained on indapamide 2.5 mg (70%). The incidence of drug-related adverse events during the double-blind period was similar between the two treatment groups. The mean change from pretreatment baseline to endpoint in serum potassium was -0.2 mEq/L (-0.2 mmol/L) in the indapamide 1.25 mg treatment group, compared with -0.4 mEq/L (-0.4 mmol/L) in the indapamide 2.5 mg treatment group. CONCLUSIONS: Indapamide 1.25 mg given once daily for 8 weeks was as effective as 2.5 mg once daily in reducing systolic and diastolic blood pressure in patients with mild to moderate hypertension. PMID- 7798070 TI - Treatment of drop attacks with nifedipine: a case report. AB - Drop attacks are sudden, unexpected, nonsyncopal falls, which are not preceded or accompanied by loss of consciousness, dizziness, lightheadedness, or loss of balance. They can be a manifestation of epilepsy, brain stem tumors, and a variety of other conditions. In the elderly, they have been associated with vertebrobasilar insufficiency, cervical spondylosis, or both. However, the specificity and etiology of drop attacks have come under some scrutiny in recent years. The patient described in this case report experienced frequent drop attacks that were effectively prevented with nifedipine. Possible pathophysiologic mechanisms are discussed and the relevant literature is reviewed. PMID- 7798071 TI - Screening for lead poisoning in a suburban practice. PMID- 7798072 TI - Bed rest, exercises, or ordinary activity for acute low back pain? PMID- 7798073 TI - Quinine and leg cramps. PMID- 7798074 TI - Parent drug use, parent personality, and parenting. AB - This study examined the relationship of parent drug use and specific parent personality traits with four indicators of the parent-child bond: affection, child-centeredness, involvement, and nonconflictual relations. The participants (N = 71) were young mothers or fathers who have participated in a longitudinal study of 1,000 children and their parents from 1975 to the present. They answered a self-administered questionnaire about themselves and their oldest child. Regression analyses indicated that the domains of parent drug use and parent personality had independent effects on most of the parent-child variables. Specific parent personality traits buffered the effect of drug use on aspects of the bond. The implications of these findings are that reducing parental drug use can have direct and positive effects on the bond and can enhance some parent personality traits, thus strengthening the bond. Protective personality characteristics can mitigate the impact of drug use on the bond. PMID- 7798075 TI - The influences of goal-related action and goal information on children's perceptions of trying and wanting: an action-perception approach. AB - The influences of goal-related actions and goal information on children's try-and want perceptions were investigated with an action-perception approach (i.e., Heider, 1958). Kindergartners, second graders, and fifth graders heard stories that depicted actors engaged in one action, that same action three times, or three equifinal actions to attain a positive or negative goal. The children rated how much actors tried and wanted to attain the goal. The findings indicate that the actors who engaged in only one action were perceived to have tried and wanted the least, and the actors who engaged in equifinal actions were perceived to have tried and wanted the most. The actors who engaged in one action were not significantly differentiated from those who engaged in repetitive actions. However, the actors who engaged in repetitive actions were significantly differentiated from those who engaged in equifinal actions. For try ratings only, the children made all expected differentiations of actors by goal-related action in negative goal conditions, whereas fewer differentiations were made of actors in positive goal conditions. Age-related findings indicate that only younger children perceived that the actors who pursued positive goals tried and wanted more than those who pursued negative goals. PMID- 7798076 TI - Gifted and talented: fourth-, fifth-, and sixth-grade students' evaluations of a gifted program. AB - A pull-out program for gifted students was evaluated in reports (qualitative evaluations) from a sample of 60 program participants from the fourth, fifth, and sixth grades. The students identified six areas in their evaluations: cognitive aspects, program satisfaction, self-expression, self-esteem, boredom, and learning environment. Students who identified cognitive aspects of their program also were likely to identify program satisfaction and not being bored. Statements about opportunities to be self-expressive were made more by girls than by boys and more by fifth and sixth graders than by fourth graders. PMID- 7798078 TI - Secrets and reasons for secrecy among school-aged children: developmental trends and gender differences. AB - The substance and dynamics of secrets were elicited and analyzed for 180 children at three grade levels, to examine developmental trends and gender differences. The recorded frequencies were subjected to loglinear analyses. The results, which revealed a grade effect regarding topics of secrets, indicated a developmental shift in topics with age from secrets pertaining to possessions to secrets pertaining to interpersonal relations, heterosexual involvement, and moral transgressions. A grade effect also emerged regarding reasons for secrecy; a shift was indicated from need for exclusiveness typical of younger children to socially embedded reasons for secrecy characteristic of older children. A gender main effect regarding topics of secrets indicated that boys more often than girls bear secrets pertaining to possessions and moral transgressions, whereas girls tend more often than boys to bear secrets pertaining to family issues. No gender effect was evident, however, in regard to reasons for secrecy. The developmental trends in both aspects of secrecy investigated may be conceived in the framework of a dual shift from separateness to relatedness and from true latency to late latency. PMID- 7798077 TI - Chinese adolescents' perceptions of parenting styles of fathers and mothers. AB - Father Treated and Mother Treated subscales of the Parent Image Differential were used to assess recalled parental treatment styles of 2,150 Chinese secondary school students. Results from reliability and factor analyses showed that both scales were internally consistent, and two factors (Concern and Restrictiveness) were abstracted from each of these scales. The data on gender differences in parenting revealed significant differences, across socioeconomic classes, between paternal and maternal treatment styles, with the fathers perceived to be relatively more restrictive and showing less concern than the mothers. The data suggest that differences between paternal and maternal treatment styles exist in the Chinese context but that signs of gradual change in the differences are appearing. PMID- 7798080 TI - Characteristics of school children who are choosy eaters. AB - Choosiness, manifested in refusal of foods, eating little, and disinterest in food, was studied with regard to prevalence, stability, sociodemographic characteristics, health problems, weight, and associated problem behaviors in a sample of 240 Swedish primary school children. Questionnaires were used, and data on sociodemographic variables, health problems, weight, and height were collected from child health-care and school health records. Choosiness was present in one third of the children, but only 8% showed choosy behavior both at home and in school. The choosy children had no more health problems than others, nor were they significantly thinner. Choosiness was not related to gender, social class, or ethnic background. The choosy children had modestly elevated levels of externalizing, hyperactive, and internalizing behavior. The choosy children with a history of refusal to eat in infancy or preschool age had more pronounced choosy behavior and had more problem behaviors than the other choosy children. Choosiness can not easily be categorized within an eating disorders or main problem syndromes of childhood frame of reference. PMID- 7798079 TI - Educational and occupational aspirations of "common man" boys: Kahl's study revisited. AB - The relationships between parents' getting-ahead-getting-by orientations, adolescents' perceptions of those parental orientations, and aspirations for adolescents with different levels of intellectual ability and from various social status backgrounds were examined. Data were collected from 516 Australian 16-year olds (250 boys, 266 girls) and their parents. The adolescents were classified into four contexts defined by the median split of scores on intellectual ability and family social status. Within each ability-status context, relationships among the variables were examined by constructing regression surfaces that were formed from models that included terms to test for possible linear, interaction, and curvilinear associations. The findings suggest that (a) in each context, perceptions of parents' orientations had strong associations with adolescents' aspirations; (b) for adolescents from low ability-lower status contexts, perception of parents' orientations acted as a threshold variable such that they were related to aspirations only at medium to high perception levels; and (c) in each context, parents' aspirations were related to adolescents' educational aspirations at each level of adolescents' perceptions of parents' orientations. PMID- 7798081 TI - Measuring grade-school children's ability to represent the Euclidean horizontal coordinate. AB - Seventy-five grade-school children were administered three tasks that measured their ability to represent the Euclidean horizontal coordinate: a traditional water-level test (WLT) that used a square-shaped vessel, a WLT that used a spherical vessel, and a task that used a crossbar apparatus. The latter two tasks differed from the traditional task in terms of the degree to which the apparatus presented a frame of reference that conflicted with environmental Euclidean coordinates. Performance was analyzed according to Piaget and Inhelder's (1956) stage-scoring system; that is, the testing procedures (a) allowed children to inspect the apparatus when it was rotated to discrete orientations; (b) corrected initial errors; and (c) included 0 degrees, 30 degrees, 60 degrees, and 90 degrees trials. Age-related stages were identified on each task. Levels of performance on one task were significantly correlated with levels on each of the other two tasks. Performance was less accurate on the traditional WLT than on either of the other two measures. These results provide evidence of the validity of the alternative tasks to measure children's horizontality representation. The findings suggest that horizontality assessment procedures should include orthogonal and oblique rotations and contain an inspection phase. Use of apparatuses with conflicting frames of reference renders tasks more difficult but is not necessary to observe age-related developmental progress during the grade school years. PMID- 7798082 TI - Alexithymia and physiological reactivity to emotion-provoking visual scenes. AB - Alexithymia, a syndrome that involves a marked inability to name feelings, has been linked to psychosomatic illness. This study addressed the question of whether alexithymic tendencies are related to heightened levels of autonomic response to extrinsic cues. Alexithymia was assessed with the Toronto Alexithymia Scale and by the emotional content of stories written to five TAT-like printed pictures. Seventy-two college students were exposed to a series of emotion provoking slides while their heart rates and electrodermal responses were recorded. Results indicated a trend for alexithymic tendencies to be associated with less heart rate increase and fewer electrodermal responses while viewing the slides. Alexithymia was also associated with a small but significant elevation in baseline heart rate. These findings are discussed as part of a pattern of results which calls into question the hypothesis that alexithymia is related to illness because it produces hyperarousal to situational stressors; it is suggested that future research on the relationship between alexithymia and health status should be broadened to explore health-maintenance behaviors and other possible mechanisms. PMID- 7798083 TI - Assessment of personality disorders in anorexia nervosa and bulimia nervosa. A comparison of self-report and structured interview methods. AB - Interest in assessing Personality Disorders (PDs) in association with anorexia nervosa (AN) and bulimia nervosa (BN) has been accompanied by the development of several structured interview and self-report measures. In an attempt to see how the self-report Millon Clinical Multiaxial Inventory (MCMI-II) compared with the Structured Clinical Interview for DSM-III-R (SCID-II) in the assessment of PDs, we gave both instruments to 43 inpatients with a diagnosis of AN or BN. Correlation coefficient values for both categorical and dimensional comparisons were generally less than .4. Although comparable rates of positive PDs occurred for each of the three clusters (A: 30.2% vs. 34.9%, B: 25.6% vs. 18.6%, and C: 62.8% vs. 81.4% for SCID-II vs. MCMI-II), agreement for individual diagnosis and individual subjects was poor. In conclusion, the MCMI-II did not prove to be a reliable instrument for assessing axis II PDs in patients with AN and BN when compared with the SCID-II. PMID- 7798084 TI - A comparison of the structured clinical interview for DSM-III-R and clinical diagnoses. AB - The relationship between diagnoses generated by the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID) and by nonstructured psychiatric interviews was examined. The purposes were to evaluate which DSM-III-R diagnoses were most reliably chosen, and to compare diagnostic practices between two clinical sites. Diagnoses generated by researchers using the patient version of the SCID and by psychiatric interviews were compared for 100 patients. The participants had been randomly assigned to one of two acute treatment sites within the same institution, as part of a larger study of an alternative to inpatient hospitalization. Overall reliability between the SCID and the clinicians, as determined by weighted Kappa, was poor. There was considerable variability among the major diagnostic categories, with higher agreement for schizophrenia and bipolar disorder than for others. The agreement for schizoaffective disorder was extremely low. There were also significant differences in the patterns of diagnosis between the two sites. The patient version of the SCID appears to produce results that are very different from clinical practice, which, in turn, may be influenced strongly by location. PMID- 7798085 TI - Changes in self-destructiveness of borderline patients in psychotherapy. A prospective follow-up. AB - Thirty-seven female inpatients with borderline personality disorder were followed prospectively for up to 5 years to assess changes in two forms of self destructiveness: suicidal behavior/ideation, and self-harm behavior/ideation. It was found that suicidal behavior declined significantly at 1-, 2-, 3-, 4-, and 5 year follow-up; self-harm behavior showed trends but no significant decline over 5 years. Ideation (both suicidal ideation and self-harm) did not decline notably. Three alternate courses of self-harm behavior are identified: "fluctuating," "consistently low," and "steadily declining." The majority of patients fell in the fluctuating category. The fluctuating group showed higher baseline dysphoria than did the consistently low group, while the latter reported higher baseline drug use. Intercorrelations showed that self-harm behavior and suicidal behavior were not associated, nor were suicidal behavior and suicidal ideation. Clinical and research implications are discussed. PMID- 7798086 TI - An etiological model of attempted suicide among Vietnam theater veterans. Prospective generalization to a treatment-seeking sample. AB - The etiology of attempted suicide was investigated using both retrospective and prospective data from 402 Vietnam theater veterans who were receiving treatment in the Department of Veterans Affairs Posttraumatic Stress Disorder Clinical Teams Program. An etiological model that was developed previously for a community sample of Vietnam theater veterans was examined for its generalizability to this treatment-seeking sample. Structural equation modeling was used to first determine the similarity of significant paths in the treatment-seeking and community samples, and then to examine the applicability of the community-based model to the treatment-seeking sample. The community-based model achieved a very high fit with reasonably good parsimony with the treatment-seeking data. Causal paths in the treatment-seeking sample mirrored those in the community sample in that psychiatric symptoms (including posttraumatic stress disorder) were the sole factors contributing directly to attempted suicide. Traumatic military experiences played a substantial role, but only indirectly as they contributed to the development of psychiatric symptoms. The similarity of findings for previous and subsequent attempts eliminated a possible ambiguity in the direction of causation modeled for previous attempts. PMID- 7798087 TI - Psychiatric morbidity associated with acquired immune deficiency syndrome-related grief resolution. AB - This study examined acquired immune deficiency syndrome (AIDS)-related grief resolution and psychiatric morbidity in 286 human immunodeficiency virus (HIV) positive and HIV-negative gay men examined between 1989 and 1993 in San Diego, CA. Psychiatric morbidity, mood ratings, and bereavement assessments were obtained using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scales for Depression and Anxiety, and Texas Revised Inventory of Grief. Sixty percent of the men (N = 171) reported a loss within the previous 12 months. Eighteen percent of the bereaved met criteria for unresolved grief. No differences were evident in lifetime psychiatric disorders, yet men with unresolved grief demonstrated an elevated prevalence of current major depression and panic disorder when compared with resolved grievers. Clinician sensitivity to the grief process and its relationship to psychiatric complications is an important component of comprehensive psychiatric and medical care of men at high risk for HIV during this era of AIDS. PMID- 7798088 TI - Effects of a natural disaster on immigrants and host population. AB - The psychosocial effects of the 1989 Newcastle earthquake on 250 immigrants from non-English-speaking backgrounds (NESB) were compared with a matched sample of 250 Australian-born subjects. The NESB subjects had higher levels of both general (General Health Questionnaire-12) and event-related (Impact of Event Scale) psychological morbidity. Furthermore, NESB females had the highest levels of distress, particularly those who were older on arrival in Australia and those who experienced high levels of disruption. The results suggest that NESB immigrants, particularly women, appear to be more at risk for developing psychological distress following a natural disaster. However, level of exposure and an avoidance coping style contributed more substantially to psychological distress than ethnicity. PMID- 7798089 TI - Mothers with severe mental illness caring for children. AB - This research identifies and describes the Massachusetts population of Department of Mental Health (DMH) case-managed women with severe mental illness who are caretakers of their minor children (N = 314), and compares their demographic and clinical characteristics and service utilization with those of a matched, randomly selected group of DMH case-managed noncaretaking women (N = 328) using the Client Tracking System database. Caretakers were significantly younger, had less formal education, and had higher rates of marriage than did noncaretakers. They are diagnosed more often with major affective disorders and less often with psychotic disorders. Caretakers demonstrate higher levels of functioning and are less likely to have a representative payee. Although caretakers function better, the groups do not differ significantly in their use of DMH services. This is the first systematic, statewide effort to specify the unique characteristics of this substantial group of women with severe mental illness who are caring for their children. PMID- 7798090 TI - Tardive dyskinesia prevalence rates during a ten-year follow-up. AB - We followed up patients in the State Psychiatric Hospital Mauer-Ohling, Mauer Ohling, Austria, who had been examined in 1982 to determine the prevalence of tardive dyskinesia (TD). Of the 861 patients examined in 1982, 270 were still in hospital 10 years later. Only these patients were included in our study. The SKAUB (Skala fur abnorme unwillkurliche Bewegungen, i.e., The German version of the Abnormal Involuntary Movement Scale) was used to quantify the occurrence of TD. The prevalence rate of TD was 3.7% in 1982 and 12.7% in 1992. The 1992 prevalence rate in patients who had not shown TD symptoms in 1982 was 11.4%. The major risk factor for TD was advanced age. PMID- 7798091 TI - Does neurosurgery for obsessive-compulsive disorder produce personality change? AB - Seventeen patients suffering from intractable obsessive-compulsive disorder treated with neurosurgery were assessed before surgery and a mean 10 +/- 5.1 years after surgery. Change in personality was assessed using a special 34-item schedule on patients and informants. The majority of subjects had not noted any significant changes in personality. The subjects were rated by themselves and their informants to have improved overall in the following characteristics: they were less obsessional, cried less, demonstrated a greater depth of feelings, laughed more, were more sociable, and were less anxious or dependent. Six subjects were judged by informants to have improved in their degree of obsessionality, which was distinguishable from the impact on obsessive-compulsive symptoms. The traits that showed an overall negative change were initiative/drive and energy level. Four subjects (2/4 open and 2/13 stereotactic surgery) were judged to have a negative personality change. Ratings of neuroticism, anxiety, depression, and capacity for pleasure showed significant improvement. We conclude that while most obsessive-compulsive disorder patients treated with stereotactic surgery do not experience a personality change, a small proportion report a positive or negative impact. Of note is the improvement in obsessionality in some patients, and an adverse personality change of the "frontal lobe type" in a few patients. PMID- 7798092 TI - Long-term results of aseptic cemented Charnley revisions. AB - One hundred eighty low-friction arthroplasties of the hip in 164 patients in first-time revision surgery were operated between 1973 and 1985. This series used only cement fixation, and aseptic loosening and femoral stem fractures were the only indications for revision. The average follow-up period was 11.5 years. Intra operative and postoperative complications were frequent: femoral shaft fracture (13 cases), femoral shaft perforation (12 cases), deep infection (14 cases), and dislocation (15 cases). Twenty-eight hips were rerevised or removed (resulting in a total cumulative probability of rerevision of 20% after 16 years, according to survivorship analysis). Nineteen cups were rerevised (13% after 16 years, according to survivorship analysis), and 24 femoral stems were rerevised (16% after 16 years, according to survivorship analysis). Radiographic cup and femoral loosening appeared in 29 and 36 cases, respectively (24 and 22% after 16 years, respectively, according to survivorship analysis). Good results were observed when there was a healthy and intact bone bed, whereas poor results were related to inadequate bone stock in the acetabulum and femur. Radiolucent lines were frequent in both components; radiolucent lines less than 2 mm wide were frequent in acetabular zone 1. Pistoning of the prosthesis and the cement within the bone and calcar pivot was the most frequent type of stem loosening. PMID- 7798093 TI - Relationship of surgical volume to short-term mortality, morbidity, and hospital charges in arthroplasty. AB - In 1992, the Agency of Health Care Administration in Tallahassee, Florida, started releasing, as part of the patient discharge information, the names of the treating physicians, in addition to demographic and diagnostic data. This information is available to the general public for a small price and is being used by health planners, hospital administrators, finance departments, third party payers, and other agencies involved in health care. Patient discharge information was used to assess the effects of volume on the short-term outcome of primary and revision hip and knee arthroplasty as a function of surgeon and hospital in the State of Florida, during 1992. A total of 19,925 primary and 2,536 revision arthroplasties of the hip and knee were performed during 1992 in Florida and were available for study. After the doctors and hospitals were arbitrarily divided into three case volume groups (low, medium, high), results showed that in primary arthroplasty, surgeons with a low volume of primary cases (< 10) have a significantly higher mortality rate (24%), higher average charges ($25,000), and increased average length of hospital stay (9.3 days). In revision surgery, physicians with a low volume of cases (< 10) have a higher mortality rate (13%) and increased average length of hospital stay (9.8 days). Patients discharge information has many potential uses for investigators interested in the short-term outcome of arthroplasty. In their present form, these databases should not be released to the general public or the media. Lastly, the volume-outcome relation for a specific surgical procedure should, in addition to case severity, account for characteristics affecting the degree of technical difficulty. PMID- 7798094 TI - Patient outcomes following unicompartmental or bicompartmental knee arthroplasty. A meta-analysis. AB - The purpose of this study was to summarize the literature describing patient outcomes following unicompartmental and bicompartmental knee arthroplasty. Original studies were included in this meta-analysis if they enrolled 10 or more patients at the time of an initial knee arthroplasty and measured patient outcomes using a global knee rating scale. Forty-six studies on unicompartmental prostheses and 18 studies on bicompartmental prostheses met these criteria. For unicompartmental studies, the total number of enrolled patients was 2,391, with a mean enrollment of 47 patients and a mean follow-up period of 4.6 years. The mean patient age was 66 years; 67% were women, 75% had osteoarthritis, and 16% underwent bilateral knee arthroplasty. The mean postoperative global rating scale score was 80.9. The overall complication rate was 18.5% and the revision rate was 9.2%. Studies published after 1987 reported better outcomes, but also tended to enroll older patients and patients with osteoarthritis and higher preoperative knee rating scores. For bicompartmental studies, the total number of enrolled patients was 884, with a mean enrollment of 44 patients and a mean follow-up period of 3.6 years. The mean patient age was 61 years; 79% were women, 31% had osteoarthritis, and 29% underwent a bilateral arthroplasty. The mean postoperative global rating scale score was 78.3. The overall complication rate was 30% and the revision rate was 7.2%. Although bicompartmental studies reported lower mean postoperative global rating scale scores, these studies tended to enroll patients with worse preoperative knee rating scores. Recent improvements in patient outcomes following unicompartmental knee arthroplasty appear to be due, at least partially, to changes in patient selection criteria. Patient outcomes appear to be worse for bicompartmental arthroplasties than for other prosthetic designs; however, patients enrolled in these studies had more poorly functioning knees before surgery and actually had greater absolute improvements in global knee rating scores. PMID- 7798095 TI - Single-stage, bilateral, cementless total hip arthroplasty. AB - Single-stage, bilateral, cementless total hip arthroplasties were performed in 92 patients (184 arthroplasties) between March 1984 and December 1989. The clinical and radiographic findings were retrospectively evaluated, and the effects of weight bearing on the clinical and radiographic outcomes of the patients' prostheses were assessed. With a follow-up period ranging from 24 to 77 months (average, 44 months), the postoperative Harris hip scores averaged 94.6. Radiographic assessment at the most recent follow-up examination showed that 70% of the femoral components were optimally fixed, 26% were stable, and 4% had failed. Ninety-six percent of the acetabular components were optimally fixed. There were six acetabular component failures. These results indicate that single stage, bilateral, cementless total hip arthroplasty can be performed without compromise to either hip if initial fit is achieved in both the metaphyseal and diaphyseal portions of the femur. Moreover, weight bearing did not adversely affect the initial stability and possible bone ingrowth, further implicating initial rigid fixation as paramount among the factors influencing the amount of ingrowth into the prosthesis. PMID- 7798096 TI - Bone ingrowth and wear debris in well-fixed cementless porous-coated tibial components removed from patients. AB - Bone ingrowth and the distribution of wear debris within the porous coating of 13 primary cementless porous-coated tibial components removed for reasons unrelated to fixation or infection were quantitatively described. The average length of implantation was 15.3 months (range, 3-30 months). The implants were all of the same design, made for Ti6A14V with a commercially pure titanium fiber-metal porous coating, which covered the undersurface of the tray and the four fixation pegs. In all but one component, supplemental screw fixation was used. The average extent of bone ingrowth within the tray was 27.1 +/- 16.1%, and the average volume fraction was 9.5 +/- 7.5%. There was significantly more bone ingrowth within the fixation pegs than within the tray and also more bone ingrowth in the anterior half of the tray than posteriorly. There was no correlation between the amount of bone ingrowth and the length of implantation, age, or sex of the patient; however, the depth and orientation of the resection plane were found to correlate with the topographic distribution of bone ingrowth. Particulate debris appeared to gain access to the interface via soft tissue pathways both at the periphery and through the holes for adjuvant screw fixation. PMID- 7798097 TI - Health and quality of life before and after hip or knee arthroplasty. AB - The impact of hip and knee arthroplasty based on the patients' own evaluations of their health, quality of life, and physical ability was assessed using a cross sectional study design. The eligibility criteria were a diagnosis of primary arthrosis, primary operation, and total joint arthroplasty. Preoperative hip and knee patient groups were compared with similar groups who underwent arthroplasty 2 or 5 years previously. Subjective health outcome was assessed with the Nottingham health profile and a 15-dimensional, health-related quality of life measure. Patients' physical ability was assessed using a measure of activities of daily living. Major improvements were observed for pain, sleep, range of motion, and physical ability. However, after surgery, patients were less healthy than the general population of the same age. The health status of patients operated on 2 or 5 years ago was similar, suggesting that health gains persist for several years. PMID- 7798098 TI - Implant standardization for total hip arthroplasty. An implant selection and a cost reduction program. AB - Total hip arthroplasty (THA) has been targeted by the United States federal government for cost control because of its high cost and rising incidence in the aging population. The hospital cost for THA during the 1980s was controlled by utilization review and a reduction in the volume of services delivered for each THA. The single largest increase in the cost of THA during the 1980s was the cost of hip implants. The Lahey Clinic Hip Implant Standardization Program was developed to provide objective guidelines for hip implant selection. These guidelines are based on the demands a patients is expected to place on his or her hip prosthesis. Because not every patient requires an expensive high-demand hip prosthesis, the standardization program also has the potential to reduce the hospital cost for hip implants without compromising patient care. Patients are assigned to four demand categories based on five objective criteria: age, weight, expected activity, general health, and bone stock. Selection of the prosthesis in each of the four demand categories is intended to match the implant's capacity with expected patient demand. The standardization program was retrospectively applied to 103 THAs performed during 1991. Analysis of variance demonstrated that patient variables and demand categories were statistically significant groupings. The cost of hip implants would have been reduced by 25.7% with the Lahey Clinic Hip Implant Standardization Program. A prospective outcome study is required to determine the long-term validity of this standardization program. PMID- 7798099 TI - Optimal timing of wound drain removal following total joint arthroplasty. AB - Closed suction drains reduce postoperative hematoma formation, but create an entry portal for bacteria and thus increase the risk of infection. This study attempts to establish when the risks of wound drainage outweigh the benefits. In a prospective clinical trial, wound drains were used in all patients having a total knee or total hip arthroplasty. Timing of drain removal and amount drained were recorded. Drain-site swabs were sent with drain tips for bacteriology. Results suggest that the likelihood of bacterial colonization increases while wound drainage decreases with time. The authors conclude that the optimal time to remove drains is 24 hours after total joint arthroplasty. PMID- 7798101 TI - Patellofemoral complications following total knee arthroplasty. Correlation with implant design and patient risk factors. AB - Results of 211 total knee arthroplasty operations were retrospectively evaluated to identify patients with knees at greatest risk for the development of patellofemoral complications and to determine the incidence and type of patellofemoral complications associated with different patellar implants. Patellofemoral complications occurred in 27 knees (12.8%). Osteoarthritis and obesity were associated with an increased incidence of patellofemoral problems. Significantly higher rates of patellofemoral complications were noted with metal backed patellar implants and with patellar components implanted without cement. The loosening rate with cementless fixation was 13.5%. The lowest rate of patellofemoral complications following total knee arthroplasty was obtained with all-polyethylene domed patellar components implanted with cement. PMID- 7798100 TI - Hip arthroplasty in patients with chronic renal failure. AB - Patients with chronic renal failure who underwent total hip arthroplasty were retrospectively evaluated. Thirty hips in patients with renal transplants and 16 hips in patients on chronic renal dialysis were reviewed. The average follow-up period was 54 months. The renal transplant patients exhibited generally satisfactory results. Their postoperative course was comparable to that of patients with avascular necrosis undergoing hip reconstruction without underlying renal disease. However, patients undergoing hip arthroplasty while on chronic renal dialysis had poor results (81%), including a deep infection rate of 19%. It was concluded that total hip arthroplasty be reserved for patients who are expecting a renal transplant or preferably those who have already received a successful transplant. PMID- 7798102 TI - An unusual cause of thigh pain after total hip arthroplasty. AB - The aim of total hip arthroplasty surgery is to relieve pain. There are many postulated causes of thigh pain following total hip arthroplasty, some of which are not easily corrected. Muscle hernia as a result of hip surgery is a cause of thigh pain that is disabling, relatively easy to diagnose, and may be preventable. PMID- 7798103 TI - Avascular necrosis of the hip treated by hemiarthroplasty. Results in renal transplant recipients. AB - Osteonecrosis of the femoral head is common complication in renal transplant recipients. Despite the young age of these patients, replacement arthroplasty is often used in treating symptomatic individuals. Between 1983 and 1990, 22 cemented biarticular hemiarthroplasties were performed in 16 consecutive patients with advanced osteonecrosis of the hip. The average interval from initial transplant to arthroplasty was 28 months (range, 11-63 months). The mean age at the time of arthroplasty was 40 years (range, 21-66 years), and all patients were treated with steroids and immunosuppressants at the time of surgery. The average preoperative Harris hip score was 27 points (range, 4-46 points). The mean follow up period was 40 months (range, 24-71 months). All patients had improvement in pain. Eighty percent of the patients reported a slight or mild limp, although only 25% demonstrated a positive Trendelenburg sign. The average postoperative Harris hip score was 88 points (range, 71-96 points), with 9 hips rated excellent, 12 good, and 1 fair. One patient fractured her acetabulum 26 months after arthroplasty, which resulted in progressive subluxation of the prosthesis. It was revised to a total hip arthroplasty. Another patient developed symptomatic aseptic loosening after 30 months. Apart from this patient there was no other radiologic evidence of loosening in the remainder of the series. Only one patient had demonstrable acetabular protrusion. Twenty percent of the hips had asymptomatic heterotopic ossification. The early results of using a cemented, biarticular hemiarthroplasty in this young group of renal transplant recipients appear encouraging. There was no evidence that this prosthesis causes accelerated acetabular erosion or early loosening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798104 TI - Rush rod fixation of supracondylar fractures above total knee arthroplasties. AB - The authors report on 22 displaced supracondylar femur fractures and total knee arthroplasties treated with Rush rod (Berivon, Meridian, MI) fixation. The average age at the time of total knee arthroplasty was 67 years. Fractures occurred at an average of 5 years after surgery. In only five cases was notch in the anterior cortex noted. The follow-up period averaged 7 years. There were no nonunions. All knees healed between 3 and 4 months after surgery. Postoperative flexion averaged 108 degrees (preoperative average, 102 degrees). Only two knees demonstrated a flexion contracture before surgery (5 degrees-10 degrees), and both had flexion contractures after surgery as well (each 10 degrees). All other knees achieved full extension. The average alignment prior to fracture was 7 degrees of anatomic valgus. At the most recent follow-up evaluation this averaged 10 degrees with two knees in 15 degrees of valgus. The only complications noted were two intraoperative technical errors. No postoperative complications occurred. For supracondylar fractures above a total knee arthroplasty, the authors suggest closed reduction, Rush supracondylar rod fixation, early range of motion, and protected weight bearing until fracture healing. In all cases, an extensive surgical procedure was not required. PMID- 7798105 TI - Insall-Burstein posterior-stabilized knee prosthesis in rheumatoid arthritis. AB - The authors reviewed 65 Insall-Burstein (Zimmer, Warsaw, IN) total condylar posterior-stabilized knee prostheses in 50 patients with rheumatoid arthritis with a follow-up period of at least 5 years (range, 5-13 years). Forty-two knees in 31 patients were evaluated using the Knee Society knee and functional rating scores. Radiographic assessment was performed using standing long radiographs (hip to ankle). Radiolucent lines were studied using fluoroscopic-centered views. Excellent or good clinical results were obtained in 95% of the cases, and the average knee score improved from 22.5 to 90 points. No cases of radiologic loosening were observed. Incomplete radiolucent lines around the tibial component were detected in only 17% and were nonprogressive. Two patients developed hematogenous late deep infection, which required removal of the prosthesis in both, followed, at a second stage, by arthrodesis in one and prosthesis reimplantation in the other. Three knees (7%) had a painful impingement of the patella. Two of these were successfully reoperated with arthroscopic debridement of the peripatellar synovial tissues. Survivorship analysis, based on endpoints such as prosthesis removal for any cause or radiologic loosening (complete radiolucent line thicker than 1 mm, tilt, or subsidence of the component), showed a cumulative success rate of 96.2% at 13 years. PMID- 7798106 TI - Micromotion secondary to axial, torsional, and shear loads in two models of cementless tibial components. AB - Tibial component loosening and lack of bone ingrowth remain serious problems in uncemented knee arthroplasty. Initial implant stability is the most important factor in achieving bone ingrowth. Eccentric axial loading causing liftoff has been identified as a potential problem, but the role of torsion and shear stability is unclear. This study assesses the micromotion in two uncemented components subjected to eccentric axial (lateral, medial, posterior, anterior), shear, and torsional loads. Four configurations were tested: Tricon M (pegs) (Smith and Nephew Richards, Memphis, TN), Genesis (stem only) (Smith and Nephew Richards), Genesis with screws, and Genesis with pegs. Nine pairs of cadaver tibias were implanted, and cyclic loads were applied. Micromotion was measured with two linear variable differential transformers. Micromotion values for each mode of loading were compared using a one-way analysis of variance. Genesis with screws had the least micromotion for all applied loads (14-33 micrometers), whereas Genesis with stem only has the maximum value of micromotion (27-212 micrometers). Genesis wit and Tricon had intermediate ranges of micromotion (32 121 and 107-140 micrometers, respectively). It is concluded that peg fixation and stem fixation are inadequate and result in significant micromotion. Stem plus screws provides the most stable fixation and may be compatible with bone ingrowth. PMID- 7798107 TI - Joint motion of bipolar femoral prostheses. AB - From 1982 to 1992, 251 bipolar hip arthroplasties were performed on 213 patients. Among them, 117 bipolar femoral prostheses were randomly selected to examine the behavior of abduction motion under weight-bearing loads. Roentgenographic motion study was performed at an average of 46.5 months after surgery (range, 2-110 months). One hundred one prostheses used in dysplastic osteoarthritic, rheumatoid, and revised failed total hip arthroplasty patients moved 18.2% at the outer bearing and 81.8% at the inner bearing, while 16 prostheses used in femoral neck fracture and osteonecrosis of the femoral head patients moved 49.7% at the inner bearing and 50.3% at the outer bearing. There was a statistical difference in the motion pattern between the two groups. The abduction motion behavior of the bipolar femoral prostheses was not affected by the length of the follow-up period, the diameter of the outer heads, or the position of the prostheses on immediate postoperative roentgenograms. PMID- 7798109 TI - Supracondylar fractures above a total knee arthroplasty: a novel use of the Huckstepp nail. PMID- 7798108 TI - Influence of disodium (1-hydroxythylidene) diphosphonate on bone ingrowth into porous, titanium fiber-mesh implants. AB - The influence of disodium (1-hydroxythylidene) diphosphonate on the bonding between bone and porous, titanium fiber-mesh implants was studied. Rectangular, porous, titanium fiber-mesh implant (15 x 10 x 2.4 mm) were implanted into the tibial bone of mature male rabbits. The rabbits were divided into six groups. Disodium diphosphonate was administered daily by subcutaneous injection to groups 1-5. Groups 1-4 received doses of 5.0, 2.5, 1.0, and 0.1 mg per kilogram of body weight per day for 8 weeks, respectively. Group 5 received a dose of 5 mg per kilogram of body weight per day for 4 weeks. Group 6 (control group) was given saline injections. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the implants were dissected out and subjected to detachment tests. The failure load, when an implant became detached from the bone or when the bone itself broke, was measured. The interface of the bone and implant was investigated by Giemsa surface staining and contact microradiography. Giemsa surface staining and contact microradiography showed that porous implant bonding to bone tissue was inhibited by a high dose of disodium diphosphonate in groups 1, 2, and 5. Soft tissue was observed at the interface. In groups 3, 4, and 6, bone tissue ingrowth was observed at the interface between the porous implant and bone tissue. Growth of bone into the porous fiber-mesh implant of a cementless prosthesis is possible if a low dose of diphosphonate below 1.0 mg per kilogram of body weight is given subcutaneously. PMID- 7798110 TI - Long-term results of cemented total hip arthroplasty in patients 45 years old or younger: a 16-year follow-up study. PMID- 7798111 TI - A note on the relative rates of degeneration in the crossed and the uncrossed retinofugal fibres in the opossum Didelphis marsupialis. AB - The rates at which the crossed and the uncrossed components of the retinofugal pathway degenerate in Didelphis has been studied by light and electron microscopical methods. We have found that in Didelphis, as in Monodelphis the two components can be clearly distinguished at the level of the chiasm. However, in contrast to the situation previously described for Monodelphis, where the uncrossed component degenerates more rapidly than the crossed, both components degenerate at the same rate. PMID- 7798112 TI - The structural relations between nerve fibres and muscle cells in the urinary bladder of the rat. AB - Intramuscular nerve fibres in the bladder of adult female rats were investigated by means of serial sections. The following observations were made. (1) Upon penetrating into the musculature the nerve bundles branch repeatedly, and almost all turn into single fibres; their axons become varicose, the Schwann cell sheath is attenuated, incomplete or absent, and the separation between axonal membrane and muscle cell membrane is reduced to tens of nanometres. (2) All single axons, and some of those within bundles, are varicose, but the characteristic of being varicose is expressed by degrees, and is not an all-or-none state. (3) Varicosities contain vesicles (mostly of the agranular type), microtubules (with little connection with the axolemma or the vesicles), some neurofilaments (scarce or absent in the best developed varicosities), mitochondria (whose size is on average smaller than those of the perikaryon, and a minute amount of endoplasmic reticulum. (4) Terminal varicosities, the true anatomical ending of an axon, are often devoid of Schwann cell sheath, are packed with vesicles, rarely contain microtubules or neurofilaments, and lie close to a muscle cell: the gap is often reduced to approximately 10 nm. (5) Schwann cells accompany the axons within the muscle strands. Unlike the area of the axonal profiles, the area of glial sheath changes little along the length of the nerve fibre, except towards its end. (6) The Schwann cell sheath around a varicosity is often incomplete; the area of the axolemma thus exposed is covered by the basal lamina, and is here referred to as a 'window'. While some varicosities have a window only a few tens of nanometres in width, others have more than one window, and some are devoid of Schwann cell altogether, so that their entire axolemma is in contact with the basal lamina. The Schwann cell never extends beyond the axon, whereas very often (and possibly always) the axon extends beyond the Schwann cell. (7) Intervaricose segments vary in length and diameter, the narrowest ones accompanying the more clear-cut varicosities. Some intervaricose segments are as small as 50 nm in diameter, contain a single microtubule and lack a Schwann cell sheath. Others, sheathed by a Schwann cell, contain a single neurofilament or no organelles at all.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798113 TI - Pathologic alterations in pre- and postsynaptic elements in aged mouse sympathetic ganglia. AB - Dysfunction of the sympathetic autonomic nervous system is an increasingly recognized, although poorly understood, complication of increasing age in experimental animals and man. In this study of young adult (4-6 months old) and aged (12-24 months old) mice we have examined the ultrastructural appearance of perikarya, dendritic processes, preterminal axons, and synapses in selected sympathetic ganglia as well as the three-dimensional structure of the dendritic arborizations of principal sympathetic neurons using intracellular injections of Lucifer Yellow. Ultrastructural examination demonstrated numerous markedly enlarged presynaptic terminal axons and synapses which distorted the contours of perikarya and dendrites of neurons within the prevertebral celiac/superior mesenteric and paravertebral superior cervical and stellate sympathetic ganglia of aged mice. Dilated preterminal axons had the distinctive ultrastructural appearance of neuroaxonal dystrophy, a pathologic process described in a wide variety of clinical and experimental entities. Dystrophic axons were identical in ultrastructural appearance in young and old animals, differing only in frequency. A distinctive type of ultrastructural alteration, characterized by markedly distended neurites containing numerous vacuoles, was confined to the superior cervical ganglia and also increased in frequency with aging. Although many intraganglionic vacuolated processes disappeared with surgical interruption of the cervical sympathetic trunk, which contains the preganglionic axons innervating the superior cervical ganglia, others persisted. In addition, the presence in some processes of admixed ribosomes, lipofuscin, or continuity with the cell body indicated that numerous neuritic alterations within aged sympathetic ganglia were likely of dendritic origin. Intracellular injections of Lucifer Yellow into principal sympathetic neurons demonstrated that the dendritic arborizations of the celiac/superior mesenteric ganglia neurons of young adult mice were significantly more complex and extensive than those of the superior cervical ganglia. Sympathetic neurons of aged superior cervical ganglia, but not superior mesenteric ganglia, appeared significantly smaller with regard to total dendritic length, extent, and branching when compared to those of young animals. In the aged superior cervical ganglia, short, stunted dendritic processes also exhibited large, focal, often multiple, swellings, a phenomenon infrequently observed in the superior cervical ganglia of young animals. The celiac/superior mesenteric ganglia of aged or young adult mouse failed to exhibit comparable dendritic swellings. PMID- 7798114 TI - Three-dimensional organization of stable microtubules and the Golgi apparatus in the somata of developing chick sensory neurons. AB - Microtubules play a role important in regulating cell shape and in mediating organelle movements. These functions are especially important in elaborately branched neurons, which have many stable microtubules that are resistant to cold and to microtubule depolymerizing drugs. We examined the three-dimensional organization of microtubules in cell bodies of cultured chick embryo sensory neurons, using confocal laser scanning microscopy. Microtubules were visualized with antibodies against alpha-tubulin and post-translationally modified forms of alpha-tubulin that accumulate in older microtubules. Optical sections were collected through neuronal somata, and the images were reconstructed in three dimensions. In neuronal perikarya a dense network of older microtubules is co localized with the Golgi apparatus. This complex of the Golgi and older microtubules usually lies beneath the cell nucleus and is oriented toward the substratum. From this region, older microtubules extend into each neurite. A cage of older microtubules extends around the nucleus to the top of the perikaryon. The stability of these microtubules was confirmed by their resistance to the depolymerizing drug, nocodazole. This arrangement of stable microtubules in a developing neuron provides a supporting cytoskeleton and a transport pathway for movement of cytoplasmic components between the Golgi apparatus, the perikaryon and developing neurites. PMID- 7798115 TI - Growth-related alterations in motor endplates of type-identified diaphragm muscle fibres. AB - Using a double-labelling technique, and dual-channel confocal microscopy, we examined the three-dimensional and two-dimensional morphologies of motor endplates on type I and II muscle fibres of 21-day-old and adult rat diaphragms. Motor endplates were visualized with fluorescein-conjugated alpha-bungarotoxin, and muscle fibre type was immunocytochemically determined using an anti-fast (type II) myosin antibody with a Cy5-conjugated label. Surface (three dimensional) and planar (two-dimensional) areas were obtained from three dimensional reconstructions of confocal optical sections of labelled endplates. Muscle fibre diameters were also measured. Total branch lengths were measured from projection images of the three dimensional reconstructions. The surface and planar areas of endplates on type I fibres at day 21 were larger than those on type II fibres, and this difference increased with maturation. In adults, the surface area of endplates was positively correlated to muscle fibre size, but such a correlation was not found at day 21. When normalized for fibre diameter, the surface areas of endplates on type I fibres were still significantly larger than those on type II fibres in both age groups. The normalized endplate surface area for type II fibres remained constant with maturation, whereas for type I fibres, the increase in endplate surface area was disproportionate to fibre growth. PMID- 7798117 TI - The medullary vascular syndromes revisited. AB - There are two major vascular syndromes of the medulla oblongata: the medial and the lateral. The medial medullary syndrome is characterized by the triad of ipsilateral hypoglossal nerve palsy with contralateral hemiparesis and loss of deep sensation. Lateral medullary infarction commonly presents with Horner's syndrome, ataxia, alternating thermoanalgesia, nystagmus, vertigo and hoarseness. Combinations of the two major syndromes occur as bilateral medial medullary, hemimedullary and bilateral lateral medullary syndromes. Each of these syndromes frequently manifests with incomplete or atypical findings depending on the extent of the lesion. Magnetic resonance imaging has been useful in the clinical diagnosis of medullary infarctions. The site of the lesion may help predict the arteries involved. PMID- 7798118 TI - Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C. AB - A 16-year-old girl presented with early-onset cerebellar ataxia, myoclonus, elevated lactic acidosis and hypogonadotropic hypogonadism. Muscle biopsy specimens revealed fibres with a "ragged" appearance with increased mitochondria and lipid droplets. Biochemical investigation revealed a deficiency of complex bc1 (complex III) of the mitochondrial respiratory chain. Genetic analysis did not show either deletions or known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) content was found in the occipital lobes accompanied by normal inorganic phosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potential. Muscle 31P-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr post-exercise recovery. These findings suggested a deficit of mitochondrial function. Therapy with vitamins K3 and C normalized brain 31P-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrinological disorder is putatively due to a mitochondrial cytopathy. Although an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome. PMID- 7798116 TI - Electrophysiological evidence of "nerve entrapment syndromes" and subclinical peripheral neuropathy in progressive systemic sclerosis (scleroderma). AB - We report the electrophysiological findings and the management of 5 subjects with progressive systemic sclerosis (PSS) and clinical evidence of nerve entrapment. Three had carpal tunnel syndrome (CTS), 1 bilateral CTS and right tarsal tunnel syndrome (TTS) and 1 Guyon's canal syndrome. Only 1 patient (with CTS) showed significant clinical improvement after surgical decompression; the other 4 demonstrated a slight recovery of conduction without lasting clinical relief after conventional treatment. To explain these failures we hypothesized that these entrapment syndromes were the clinical expression of underlying diffuse damage to the peripheral nervous system (PNS). The conduction values of nerves unaffected by entrapment syndromes were within normal limits, but almost all distal velocities were below the mean of controls. Such subclinical distal peripheral neuropathy was also verified in a selected sample of 17 patients with PSS, without clinical symptoms or signs of PNS involvement. In these 17 cases the mean distal sensory and motor conduction findings of the median, ulnar, sural and tibial nerves were significantly lower than those of a control group, while no significant differences were found in the more proximal tracts of the same nerves. Furthermore, 3 of the 17 patients showed classical electrophysiological evidence of TCS and TTS without any clinical symptoms. We conclude that the subjects with PSS had subclinical polyneuropathy which may become plain polyneuropathy or nerve entrapment syndromes perhaps induced by other risk factors. PMID- 7798120 TI - Cold: a risk factor for stroke? AB - A retrospective study was performed to investigate seasonal variation in stroke incidence and to evaluate the hypothesis that cold might be a risk factor. Data were obtained from the central registry of the Hospital de S. Joao, Porto, Portugal, concerning 4048 patients consecutively admitted for cerebrovascular disease during a period of 33 months. Monthly admissions for stroke and its subtypes were related to mean values of ambient temperature using linear correlation. There was a strong inverse correlation between average temperature and total admissions for cerebrovascular disease (r = -0.72, P < 0.00005), intracerebral haemorrhage (r = -0.66, P < 0.00005), ischaemic stroke (r = -0.46, P = 0.007) and transient ischaemic attack (r = -0.41, P = 0.017). These correlations were independent of any seasonal variation in the number of hospital admissions due to all causes. No relation was found between temperature and subarachnoid haemorrhage. The rhythmometric analysis showed the presence of a statistically significant rhythm with an acrophase in the coldest months. These results support the hypothesis of stroke being a chronorisk disease to which cold might represent a triggering factor. PMID- 7798119 TI - Multiple paraneoplastic syndromes in a patient with antibodies to neuronal nucleoproteins (anti-Hu). AB - We report the clinical and autopsy studies of a patient with an unusual combination of multiple paraneoplastic neurological syndromes in association with antibodies to a 35-40 kDa neuronal nucleo-protein (anti-Hu). Neurological disease preceded the detection of a small cell carcinoma of the lung. The patient had combined sensory and motor neuronopathy or neuropathy, cerebellar degeneration, brain-stem and limbic encephalitis, and clinical evidence of the Lambert-Eaton myasthenic syndrome and gastrointestinal pseudo-obstruction of paraneoplastic origin. PMID- 7798121 TI - Dizziness following head injury: a neuro-otological study. AB - Dizziness is a frequent and debilitating complications of head injury and accounts for increasing numbers of medico-legal claims. A detailed neuro otological study was carried out from the records of 100 patients with post traumatic dizziness to explore the neuro-otological basis of their symptoms: 50 patients presenting for medico-legal purposes (group I) and 50 presenting for management of their vestibular symptoms (group II). The two groups showed a similar sex distribution, a similar range of causes of head injury and similar severity of head injury (72 minor, 24 moderate and 4 severe). Of the 100, 88 showed at least one audio-vestibular abnormality on testing. Vertigo of the benign positional paroxysmal type was the commonest vestibular diagnosis in both groups (61/100), and only 8 patients showed central vestibular abnormalities. Fifty-three patients had audiometric abnormalities attributable to the head injury, the commonest of which was a high-tone sensorineural hearing loss. There was no significant difference in the incidence of any of the abnormalities in the medico-legal group (group I) when compared with the symptom management group (group II). The results provide strong evidence for an organic basis to recurring dizziness after head injury, whether or not a claim for compensation is pending, and emphasize the need for specialist neuro-otological investigation if abnormalities are to be identified and managed correctly. PMID- 7798123 TI - A soluble form of tumour necrosis factor receptor in cerebrospinal fluid and serum of HTLV-I-associated myelopathy and other neurological diseases. AB - Paired samples of cerebrospinal fluid (CSF) and serum from 17 patients with human T-cell lymphotrophic virus I (HTLV-I)-associated myelopathy, 5 patients with multiple sclerosis and 11 controls with non-inflammatory disorders (migraine, idiopathic epilepsy and myelopathy of unknown aetiology) were examined by enzyme linked immunosorbent assay for the presence of the 60-kDa soluble form of tumour necrosis factor receptor (sTNF-R). The results were compared with blood-CSF barrier function, cell count and the intrathecal synthesis of HTLV-I antibodies. No correlation could be demonstrated. High levels of sTNF-R were found in CSF of patients with HTLV-I-associated myelopathy and multiple sclerosis. In addition, intrathecal sTNF-R was also detected in the patients with non-inflammatory diseases, indicating that sTNF-R is definitively a normal constituent of CSF. PMID- 7798125 TI - Acute necrotizing measles encephalitis in a child with AIDS. PMID- 7798124 TI - Beneficial vascular and metabolic effects of cobalt-ATP in spontaneously hypertensive rabbits with diffuse chronic cerebral ischaemia. AB - The in vivo effects of adenosine triphosphate (ATP) have not been investigated in cerebrovascular diseases. The use of the long-acting cobalt-ATP complex (Co-ATP) permits us to observe the effects of ATP without the influence of its metabolites. This study was designed to compare the effects of intravenous Co-ATP on the cerebral blood flow (CBF), polarographically detected oxygen currents (O2a), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose in 13 normotensive (NT) rabbits to those in 14 stroke-prone spontaneously hypertensive (HT) animals. CBF was measured by the hydrogen and heat clearance methods. In response to Co-ATP, MABP decreased and CBF increased significantly in both groups. The decrease in MABP was more marked in HT rabbits, while CBF response was 25% smaller than in NT animals. The ratio of O2a to CBF diminished moderately and simultaneously with the CBF increase in NT rabbits. In HT rabbits, the decrease in O2a/CBF was larger and began when CBF response reached its maximum. We suggest that despite the restricted CBF response, long-acting ATP should still be taken into consideration as a supplementary treatment of hypertensive encephalopathy because of its beneficial effects on cerebral metabolism and hypertension. PMID- 7798126 TI - Rapid aggravation of aphasia by vigabatrin. PMID- 7798122 TI - Spontaneous internal carotid artery dissection: early diagnosis and management in 44 patients. AB - First symptoms and initial clinical, ultrasonographic and neuroradiological findings ascertained a mean of 5.6 days (SD = 5.6 days), 7.7 days (7.0), and 11.2 days (8.0) after symptom onset were analysed in 44 patients who suffered a spontaneous internal carotid artery dissection (ICD) verified by magnetic resonance imaging, angiography, or both. Common symptoms signalling dissection were unilateral headache in 68%, transient ischaemic attack in 20%, and cerebral infarction in 9%. Severe pain preceded cerebral ischaemia by more than 3 days in 60% of those patients who eventually suffered a stroke. However, only 2 were admitted because of pain alone and 33 for evolving neurological deficits. During the first month, ipsilateral severe headache occurred in 89%, neck pain in 36%, ipsilateral cerebral ischaemia in 82%, ocular ischaemia in 16%, oculosympathetic palsy in 48%, and cranial nerve palsy in 5%. Recent "trivial" head or neck trauma was elicited in 41%. Doppler and duplex sonography confirmed the clinical suspicion of ICD in 91.5% and in 96% of those with a significant stenosis or occlusion. MRI demonstrated a thickened vessel wall in all 33 imaged carotid dissections and a mural haematoma in 30. None of the 32 patients who received anticoagulant treatment subsequently deteriorated. Monitoring anticoagulant treatment with ultrasonographic follow-up studies demonstrated recanalization in 70% and persistent occlusion in 30%. The results demonstrate that familiarity with the initial symptoms, especially headache, and performance of an ultrasonographic study without delay are the cornerstones of an early diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798127 TI - Improvement following interferon beta in chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 7798129 TI - Fisher's syndrome associated with chickenpox and anti-GQ1b antibody. PMID- 7798130 TI - All the news that's fit to print. The ACNM sets the record straight. PMID- 7798128 TI - Recurrent respiratory failure in a patient with 3243 mutation in mitochondrial DNA. PMID- 7798131 TI - Asthma. A comprehensive review. AB - Asthma is common among women of childbearing and childrearing age. As a primary health care provider, the certified nurse-midwife is often called upon to play a direct role in diagnosis and collaborative co-management. This article reviews the pathogenesis of asthma and its natural history during pregnancy. Patient symptoms and findings on physical examination are described in depth, enabling clinicians to detect subtle presentations and avoid common pitfalls. A section on pulmonary function tests and other laboratory tools provides a foundation for objective monitoring of pulmonary function. Environmental control measures and pharmacologic therapies are described in detail. An algorithm for treatment strategies allows certified nurse-midwives to play an active role in co management of their asthmatic patients, while a section on patient education highlights the essential teaching points her clients will require. Specific issues regarding antenatal fetal well-being and intrapartal management are discussed. With a sound knowledge base, and through their expertise in client education and counselling, the certified nurse-midwife is in a special position to optimize care for women with asthma. PMID- 7798132 TI - Using an ovarian monitor as an adjunct to natural family planning. AB - The need to identify a reliable ovulation predictor has received attention by the scientific community in recent years. For couples practicing natural family planning, a more precise identification of the fertile phase would be a welcome adjunct to their method. A home ovarian monitor invented by Professor J. B. Brown of Melbourne, Australia, enables couples to measure the principal urinary metabolite of ovarian estrogen and progesterone. The charted results reveal the hormonal pattern of the menstrual cycle and thus identify the beginning, peak, and end of the fertile period. A study involving 21 couples was conducted with the purpose of assessing overall acceptability, including ease of use, motivation, and client satisfaction. At the completion of the study, 12 couples indicated a high degree of motivation and satisfaction with the monitor. None reported difficulty with the test procedure. Increased confidence in natural family planning was cited as the most positive evaluation and the time required to perform the test, as the most negative. PMID- 7798133 TI - Assessing fit. A key indicator of family health. AB - Attending to how family members behave in relation to their emotional involvement with each other, as it is demonstrated in the family's structural, functional, communicational, and developmental patterns or fit, is essential to truly understanding the behavior of individual clients. Family assessment is important to certified nurse-midwives working with childbearing and childrearing women. Assessing families can help certified nurse-midwives to promote women's health and to assist with skill development for subsequent generations of women, children, and families. This paper is an overview of basic concepts of family assessment, with particular emphasis on clinical application of family theory. The focus is on assessing fit and on skills that the certified nurse-midwife can use for family assessment in daily clinical practice. PMID- 7798134 TI - The hsp70 gene family of Neurospora crassa: cloning, sequence analysis, expression, and genetic mapping of the major stress-inducible member. AB - The gene encoding the major heat shock-inducible member of the HSP70 family of Neurospora crassa was cloned and characterized. The 5' nontranscribed region shows the presence of consensus sequence motifs resembling the classical heat shock elements found in many heat shock-responsive eukaryotic promoters, as well as metal-responsive-element sequences. The coding region of the gene contains four introns with boundaries and internal consensus motifs typical of genes of filamentous fungi. None of the other stress-inducible hsp70 genes of fungal origin have, so far, been reported to contain introns. The sequence adjoining the transcriptional initiation zone shows the presence of prominent CT-rich stretches, characteristic of highly expressed fungal genes. The deduced amino acid sequence corresponds to a 646-residue polypeptide, with a calculated molecular mass of 70,561 Da and an average pI of 6.01, exhibiting strong sequence homology with many other eukaryotic HSP70s, with typical HSP70 family signatures 1 and 2 and a bipartite nuclear targeting sequence. Experiments with primer extension revealed the presence of one minor and two major transcriptional start sites. This gene, designated hsps-1, was mapped to a locus on the left arm of linkage group II, in close proximity to the AR-30 translocation breakpoint. PMID- 7798135 TI - Gin mutants that can be suppressed by a Fis-independent mutation. AB - The Gin invertase of bacteriophage Mu mediates recombination between two inverted gix sites. Recombination requires the presence of a second protein, Fis, which binds to an enhancer sequence. We have isolated 24 different mutants of Gin that are impaired in DNA inversion but proficient in DNA binding. Six of these mutants could be suppressed for inversion by introduction of a second mutation, which when present in the wild-type gin gene causes a Fis-independent phenotype. Only one of the six resulting double mutants shows an inversion efficiency which is comparable to that of the wild-type Gin and which is independent of Fis. The corresponding mutation, M to I at position 108 (M108I), is located in a putative alpha-helical structure, which in the homologous gamma delta resolvase has been implicated in dimerization. The properties of the M108I mutant suggest that in Gin this dimerization helix might also be the target for Fis interaction. The five other mutants that show a restored inversion after introduction of a Fis independent mutation appear to be completely dependent on Fis for this inversion. The corresponding mutations are located in different domains of the protein. The properties of these mutants in connection with the role of Fis in inversion will be discussed. PMID- 7798136 TI - Purification and characterization of 6-chlorohydroxyquinol 1,2-dioxygenase from Streptomyces rochei 303: comparison with an analogous enzyme from Azotobacter sp. strain GP1. AB - The enzyme which cleaves the benzene ring of 6-chlorohydroxyquinol was purified to apparent homogeneity from an extract of 2,4,6-trichlorophenol-grown cells of Streptomyces rochei 303. Like the analogous enzyme from Azotobacter sp. strain GP1, it exhibited a highly restricted substrate specificity and was able to cleave only 6-chlorohydroxyquinol and hydroxyquinol and not catechol, chlorinated catechols, or pyrogallol. No extradiol-cleaving activity was observed. In contrast to 6-chlorohydroxyquinol 1,2-dioxygenase from Azotobacter sp. strain GP1, the S. rochei enzyme had a distinct preference for 6-chlorohydroxyquinol over hydroxyquinol (kcat/Km = 1.2 and 0.57 s-1.microM-1, respectively). The enzyme from S. rochei appears to be a dimer of two identical 31-kDa subunits. It is a colored protein and was found to contain 1 mol of iron per mol of enzyme. The NH2-terminal amino acid sequences of 6-chlorohydroxyquinol 1,2-dioxygenase from S. rochei 303 and from Azotobacter sp. strain GP1 showed a high degree of similarity. PMID- 7798137 TI - Growth and buoyant density of Escherichia coli at very low osmolarities. AB - The growth and buoyant densities of two closely related strains of Escherichia coli in M9-glucose medium that was diluted to produce osmolarities that varied from as low as 5 to 500 mosM were monitored. At 15 mosM, the lowest osmolarity at which buoyant density could be measured reproducibly in Percoll gradients, both ML3 and ML308 had a buoyant density of about 1.079 g/ml. As the osmolarity of the medium was increased, the buoyant density also increased linearly up to about 125 mosM, at which the buoyant density was 1.089 g/ml. From 150 up to 500 mosM, the buoyant density again increased linearly but with a different slope from that seen at the lower osmolarities. The buoyant density at 150 mosM was about 1.091 g/ml, and at 500 mosM it was 1.101 g/ml. Both strains of E. coli could be grown in M9 medium diluted 1:1 with water, with an osmolarity of 120 mosM, but neither strain grew in 1:2-diluted M9 if the cells were pregrown in undiluted M9. (Note: undiluted M9 as prepared here has an osmolarity of about 250 mosM.) However, if the cells were pregrown in 30% M9, about 75 mosM, they would then grow in M9 at 45 mosM and above but not below 40 mosM. To determine which constituent of M9 medium was being diluted to such a low level that it inhibited growth, diluted M9 was prepared with each constituent added back singly. From this study, it was determined that both Ca2+ and Mg2+ could stimulate growth below 40 mosM. With Ca2+ - and Mg2+ -supplemented diluted M9 and cells pregrown in 75 mosM M9, it was possible to grow ML308 in 15 mosM M9. Strain ML3 would only haltingly grow at 15 mosM. Four attempts were made to grow both ML3 and ML308 at 5 mosM. In three of the experiments, ML308 grew, while strain ML3 grew in one experiment. While our experiments were designed to effect variations in medium osmolarity by using NaCl as an osmotic agent, osmolarity and salinity were changed concurrently. Therefore, from this study, we believe that E. coli might be defined as an euryhalinic and/or euryosmotic bacterium because of its ability to grow in a wide range of salinities and osmolarities. PMID- 7798138 TI - The TyrR protein of Escherichia coli is a class I transcription activator. AB - The purified TyrR protein and phenylalanine were sufficient to activate in vitro transcription from the tyrP promoter by wild-type RNA polymerase. Such TyrR mediated activation did not occur when the mutant alpha 235 RNA polymerase was used, indicating that TyrR is a class I transcription activator. PMID- 7798139 TI - hlyM, a transcriptional silencer downstream of the promoter in the hly operon of Escherichia coli. AB - Transcription of the hly operon of transmissible plasmids in Escherichia coli is subject to a tight regulation which also involves various chromosomal genes, such as hha. We have identified a 200-bp region within the hlyC gene, designated hlyM, which modulates hemolysin expression. The deletion of hlyM increased the activity of hly::galK fusion 20-fold. hlyM does not contain any internal promoter, nor is it capable of acting in trans. Our data suggest that the chromosomal Hha protein interacts with hlyM in order to silence the hly promoter. In addition, hlyR, a positive activator of hemolysin expression, seems to suppress the modulatory effect dictated by the Hha protein on the hlyM region. PMID- 7798140 TI - Isolation, sequencing, and mutagenesis of the gene encoding NAD- and glutathione dependent formaldehyde dehydrogenase (GD-FALDH) from Paracoccus denitrificans, in which GD-FALDH is essential for methylotrophic growth. AB - NAD- and glutathione-dependent formaldehyde dehydrogenase (GD-FALDH) of Paracoccus denitrificans has been purified as a tetramer with a relative molecular mass of 150 kDa. The gene encoding GD-FALDH (flhA) has been isolated, sequenced, and mutated by insertion of a kanamycin resistance gene. The mutant strain is not able to grow on methanol, methylamine, or choline, while heterotrophic growth is not influenced by the mutation. This finding indicates that GD-FALDH of P. denitrificans is essential for the oxidation of formaldehyde produced during methylotrophic growth. PMID- 7798142 TI - Physical mapping of the Mycoplasma gallisepticum S6 genome with localization of selected genes. AB - We report the construction of a physical map of the Mycoplasma gallisepticum S6 genome by field-inversion gel electrophoresis of DNA fragments generated by digestion of genomic DNA with rare-cutting restriction endonucleases. The size of the M. gallisepticum S6 genome was calculated to be approximately 1,054 kb. The loci of several genes have been assigned to the map by Southern hybridization utilizing specific gene probes. PMID- 7798141 TI - Nucleotide sequence of pvdD, a pyoverdine biosynthetic gene from Pseudomonas aeruginosa: PvdD has similarity to peptide synthetases. AB - Pseudomonas aeruginosa secretes a fluorescent siderophore, pyoverdine, when grown under iron-deficient conditions. Pyoverdine consists of a chromophoric group bound to a partly cyclic octapeptide. As a step toward understanding the molecular events involved in pyoverdine synthesis, we have sequenced a gene, pvdD, required for this process. The gene encodes a 2,448-residue protein, PvdD, which has a predicted molecular mass of 273,061 Da and contains two highly similar domains of about 1,000 amino acids each. The protein is similar to peptide synthetases from a range of bacterial and fungal species, indicating that synthesis of the peptide moiety of pyoverdine proceeds by a nonribosomal mechanism. The pvdD gene is adjacent to a gene, fpvA, which encodes an outer membrane receptor protein required for uptake of ferripyoverdine. PMID- 7798143 TI - Bordetella pertussis fur gene restores iron repressibility of siderophore and protein expression to deregulated Bordetella bronchiseptica mutants. AB - We report the isolation and preliminary phenotypic characterization of manganese resistant Bordetella bronchiseptica mutants with respect to deregulation of siderophore and iron-regulated protein expression. The fur gene of Bordetella pertussis was cloned by genetic complementation of this deregulated phenotype and confirmed as fur by nucleotide sequence analysis. PMID- 7798144 TI - Agrobacterium tumefaciens VirB11 protein requires a consensus nucleotide-binding site for function in virulence. AB - virB11, one of the 11 genes of the virB operon, is absolutely required for transport of T-DNA from Agrobacterium tumefaciens into plant cells. Previous studies reported that VirB11 is an ATPase with autophosphorylation activity and localizes to the inner membrane even though the protein does not contain the consensus N-terminal export sequence. In this report, we show that VirB11 localizes to the inner membrane even in the absence of other tumor-inducing (Ti) plasmid-encoded proteins. To facilitate the further characterization of VirB11, we purified this protein from the soluble fraction of an Escherichia coli extract by fusing VirB11 to the maltose-binding protein. The maltose-binding protein VirB11 fusion was able to complement a virB11 deletion mutant of A. tumefaciens for tumor formation and also localized properly to the inner membrane of A. tumefaciens. The 72-kDa protein, purified from E. coli, exhibited no autophosphorylation, ATPase activity, or ATP-binding activity. To study the importance of the Walker nucleotide-binding site present in VirB11, mutations were generated to replace the conserved lysine residue with either alanine or arginine. Expression of the virB11K175A mutant gene resulted in an avirulent phenotype, and expression of the virB11K175R mutant gene gave rise to an attenuated virulence phenotype. Both mutant proteins were present at levels three to four times higher than that of VirB11 in the wild-type strain. The mutant genes did not exhibit a transdominant phenotype on tumor formation in bacteria that were expressing wild-type virB11. The mutant proteins also localized properly to the inner membrane of A. tumefaciens, but the VirB11K175R protein appeared to be unstable after lysis of the cells. PMID- 7798145 TI - Two genes encoding uracil phosphoribosyltransferase are present in Bacillus subtilis. AB - Uracil phosphoribosyltransferase (UPRTase) catalyzes the key reaction in the salvage of uracil in many microorganisms. Surprisingly, two genes encoding UPRTase activity were cloned from Bacillus subtilis by complementation of an Escherichia coli mutant. The genes were sequenced, and the putative amino acid sequences were deduced. One gene showed a high level of homology to UPRTases from other organisms, whereas the other gene with a low level of homology to other UPRTases turned out to be the pyrR gene--the repressor of the pyr operon. The role of these genes in uracil metabolism was established by an analysis of the phenotypes of upp and pyrR mutants. PMID- 7798146 TI - The torR gene of Escherichia coli encodes a response regulator protein involved in the expression of the trimethylamine N-oxide reductase genes. PMID- 7798147 TI - Phylogenetic comparison of retron elements among the myxobacteria: evidence for vertical inheritance. AB - Twenty-eight myxobacterial strains, representing members from all three subgroups, were screened for the presence of retron elements, which are novel prokaryotic retroelements encoding reverse transcriptase. The presence of retrons was determined by assaying strains for a small satellite DNA produced by reverse transcription called multicopy, single-stranded DNA (msDNA). An msDNA-producing retron appeared to be absent from only one of the strains surveyed. DNA hybridization experiments revealed that retron elements similar to retron Mx162, first identified in Myxococcus xanthus, were found only among members of the Myxococcus subgroup; that is, each of the seven different genera which constitute this subgroup contained a Mx162 homolog. Another retron element also appeared to have a clustered distribution, being found exclusively within the Nannocystis subgroup of the myxobacteria. A retron element of the Mx162 type was cloned from Melittangium lichenicola, and its DNA sequence was compared with those of similar elements in M. xanthus and Stigmatella aurantiaca. Together, the degree of sequence diversity, the codon bias of the reverse transcriptase genes, and the clustered distribution of these retrons suggest a possible evolutionary scenario in which a common ancestor of the Myxococcus subgroup may have acquired this retroelement. PMID- 7798148 TI - Specific binding of the NikA protein to one arm of 17-base-pair inverted repeat sequences within the oriT region of plasmid R64. AB - Products of the nikA and nikB genes of plasmid R64 have been shown to form a relaxation complex with R64 oriT DNA and to function together as an oriT-specific nickase. We purified the protein product of the nikA gene. The purified NikA protein bound specifically to the oriT region of R64 DNA. Gel retardation assays and DNase I footprinting analyses indicated that the NikA protein bound only to the right arm of 17-bp inverted repeat sequences; the right arm differed from the left arm by a single nucleotide. The binding site is proximal to the nick site and within the 44-bp oriT core sequence. Binding of the NikA protein induced DNA bending within the R64 oriT sequence. PMID- 7798149 TI - Site-specific deletions of chromosomally located DNA segments with the multimer resolution system of broad-host-range plasmid RP4. AB - The multimer resolution system (mrs) of the broad-host-range plasmid RP4 has been exploited to develop a general method that permits the precise excision of chromosomal segments in a variety of gram-negative bacteria. The procedure is based on the site-specific recombination between two directly repeated 140-bp resolution (res) sequences of RP4 effected by the plasmid-borne resolvase encoded by the parA gene. The efficiency and accuracy of the mrs system to delete portions of chromosomal DNA flanked by res sites was monitored with hybrid mini Tn5 transposons in which various colored (beta-galactosidase and catechol 2,3 dioxygenase) or luminescent (Vibrio harveyi luciferase) phenotypic markers associated to res sequences were inserted in the chromosome of the target bacteria and exposed in vivo to the product of the parA gene. The high frequencies of marker excision obtained with different configurations of the parA expression system suggested that just a few molecules of the resolvase are required to achieve the site-specific recombination event. Transient expression of parA from a plasmid unable to replicate in the target bacterium was instrumental to effect differential deletions within complex hybrid transposons inserted in the chromosome of Pseudomonas putida. This strategy permits the stable inheritance of heterologous DNA segments virtually devoid of the sequences used initially to select their insertion. PMID- 7798152 TI - Nicotinate catabolism is dispensable and nicotinate anabolism is crucial in Azorhizobium caulinodans growing in batch culture and chemostat culture on N2 as The N source. AB - When Azorhizobium caulinodans was grown in chemostat cultures with N2 as the N source at a constant dilution rate of 0.1 h-1 in media with a constant concentration (50 mM) of succinate and variable concentrations (1.5 to 585 microM) of nicotinate, neither the growth yield on succinate, the specific rate of O2 consumption, nor the specific rate of CO2 production showed linear regression with the concentration of nicotinate. Moreover, for transient continuous cultures in which the nicotinate concentration was gradually lowered, growth parameters remained unchanged until an apparently critical level of 0.7 microM nicotinate was reached. Below this nicotinate level, an immediate washout of the chemostat population began. A. caulinodans nicotinate hydroxylase-negative mutant 61007, unable to catabolize nicotinate, and the wild type behaved similarly. Thus, for continuous cultures supplied with N2 as the N source, submicromolar concentrations of nicotinate both sustained pyridine nucleotide biosynthesis at sufficient levels and precluded the use of nicotinate as a catabolic substrate. Furthermore, when more nicotinate was provided, dual succinate-nicotinate limitation in continuous cultures did not occur. Finally, when nicotinate is present in suboptimal concentrations, the specific growth rate is directly proportional to the amount of nicotinate present per unit of biomass. By contrast, in batch cultures with different nicotinate concentrations and with either succinate or lactate as the carbon and energy source, anomalous growth curves were obtained. With a low concentration (1.5 microM) of nicotinate, growth on N2 occurred, albeit at low rates. With a high concentration (195 microM) of nicotinate, growth on N2 was temporarily stimulated, but nicotinate was quickly exhausted and growth was thereafter nicotinate limited. Continuous supplementation of batch cultures with nicotinate allowed only transient exponential growth followed by linear growth. Thus, also for batch cultures, nicotinate catabolism is dispensable, although a high concentration of nicotinate temporarily stimulates growth on N2. Ut us concluded that A. caulinodans is a true diazotroph. PMID- 7798153 TI - Lack of production of (p)ppGpp in Halobacterium volcanii under conditions that are effective in the eubacteria. AB - The stringent halobacterial strain Haloferax volcanii was subjected to a set of physiological conditions different from amino acid starvation that are known to cause production of guanosine polyphosphates [(p)pp Gpp] in eubacteria via the relA-independent (spoT) pathway. The conditions used were temperature upshift, treatment with cyanide, and total starvation. Under none of these conditions were detectable levels of (p)ppGpp observed. This result, in conjunction with our previous finding that (p)ppGpp synthesis does not occur under amino acid starvation, leads to the conclusion that in halobacteria both growth rate control and stringency are probably governed by mechanisms that operate in the absence of ppGpp. During exponential growth, a low level of phosphorylated compounds with electrophoretic mobilities similar, but not identical, to that of (p)ppGpp were observed. The intracellular concentration of these compounds increased considerably during the stationary phase of growth and with all of the treatments used. The compounds were identified as short-chain polyphosphates identical to those found under similar conditions in Saccharomyces cerevisiae. PMID- 7798150 TI - Identification of mycobacterium tuberculosis DNA sequences encoding exported proteins by using phoA gene fusions. AB - The activity of bacterial alkaline phosphatase (PhoA) is dependent on it being exported across the plasma membrane. A plasmid vector (pJEM11) allowing fusions between phoA and genes encoding exported proteins was constructed to study protein export in mycobacteria. Introduction of the Mycobacterium fortuitum beta lactamase gene (blaF*) into this vector led to the production in M. smegmatis of protein fusions with PhoA activity. A genomic library from M. tuberculosis was constructed in pJEM11 and screened in M. smegmatis for clones with PhoA activity. Sequences of the M. tuberculosis inserts directing the production of protein fusions in these PhoA-positive clones were determined. They include part of the already-known exported 19-kDa lipoprotein, a sequence with similarities to the exported 28-kDa antigen from M. leprae, a sequence encoding a protein sharing conserved amino acid motifs with stearoyl-acyl-carrier-protein desaturases, and unknown sequences. This approach thus appears to identify sequences directing protein export, and we expect that more extensive screening of such libraries will lead to a better understanding of protein export in M. tuberculosis. PMID- 7798151 TI - A cluster of four genes encoding enzymes for five steps in the folate biosynthetic pathway of Streptococcus pneumoniae. AB - Two genes, sulB and sulC, in a folate biosynthetic gene cluster of Streptococcus pneumoniae were identified after determination of the DNA sequence between two previously reported genes, sulA and sulD, in a cloned segment of chromosomal DNA containing a mutation to sulfonamide resistance. The gene products, SulB and SulC, correspond to polypeptides of 49 and 21 kDa, respectively. SulC has GTP cyclohydrolase activity and catalyzes the first step in the folate biosynthetic pathway. SulB apparently has dihydrofolate synthetase activity in that it complements a folC mutant of Escherichia coli and thus catalyzes the last step in the pathway. Prior work showed that SulA, a dihydropteroate synthase, and SulD, a bifunctional enzyme, catalyze three intervening steps. Mapping of the mRNA transcribed from the operon was consistent with its beginning at a promoter with a -35 site (gTGtCc) and an extended -10 site (T-TG-TAaAAT) and its termination at the end of a hairpin structure, which would give a transcript 3,745 nucleotides in length. SulC showed a considerable conservation of sequence by comparison with proven or putative GTP cyclohydrolases from four unrelated species, with 38 to 53% of the residues being identical. A similar comparison of SulB with dihydrofolate synthetases showed an identity of only 26 to 37%. Overall, comparisons of the five folate biosynthetic enzymes in different species suggest that S. pneumoniae is related more closely to other gram-positive bacteria, less closely to eucaryotes, and least closely to the gram-negative E. coli. The varied arrangements of folate biosynthetic genes in different species imply an early evolutionary period of fluidity in genomic rearrangement. PMID- 7798154 TI - The rec locus, a competence-induced operon in Streptococcus pneumoniae. AB - To study competence and the process of transformation (TFN) in pneumococci, we developed a method for isolating TFN- mutants using insertional inactivation coupled with fusions to the gene for alkaline phosphatase (phoA). One TFN- mutant transformed 2 log units less efficiently than the parent strain. Reconstitution of the mutated region revealed a locus, rec, that contains two polycistronic genes, exp10 and the previously identified recA (B. Martin, J. M. Ruellan, J. F. Angulo, R. Devoret, and J. P. Claverys, Nucleic Acids Res. 20:6412, 1992). Exp10 is likely to be a membrane-associated protein, as it has a prokaryotic signal sequence and an Exp10-PhoA fusion localized with cell membranes. On the basis of sequence similarity, pneumococcal RecA is a member of bacterial RecA proteins responsible for homologous recombination of DNA. DNA-RNA hybridization analysis showed that this locus is transcribed as a polycistronic message, with increased transcription occurring during competence. With an Exp10-PhoA chimera used as a reporter, there was a 10-fold increase in the expression of the rec locus during competence while there was only minimal expression under growth conditions that repressed competence. The TFN- mutant containing the exp10-phoA fusion produced activator, a small extracellular polypeptide that induces competence, and the expression of rec was induced in response to activator. Therefore, the rec locus is directly required for genetic transformation and is regulated by the cell signaling mechanism that induces competence. PMID- 7798156 TI - Durable remissions following prolonged plasma exchange in thrombotic thrombocytopenic purpura. AB - We evaluated the efficacy of prolonged plasma exchange (PEX) for attaining durable remissions in thrombotic thrombocytopenic purpura (TTP). A recent review using steroids or PEX in initial management showed an 80% response rate but produced a relapse rate of 67-84%. Records of 50 patients starting PEX treatment for TTP/HUS were reviewed to identify and select those whose course of treatment had ended over 1 year earlier, whether or not the result was satisfactory. Records were evaluated for outcome, especially remission associated with treatment by "prolonged" plasma exchange. "Prolonged" was defined as continuing PEX beyond the stage where a normal platelet count was attained and until evidence of hemolysis was "minimal or at least compensated." If disease activity as judged by the criteria of hemolysis became accelerated or resumed, PEX was increased by volume of FFP (e.g., from 3 to 4 L) or rate (from less than daily to daily). Of 50 consecutive patients treated by PEX for TTP/HUS there were 40 cases after which at least one year had passed since the end of treatment. These 40 patients were evaluated for the results of treatment by PEX. Eight failed to achieve remission, dying in hospital within 1 month of admission. Twenty-eight achieved remission, sustained for 1 year or more in all. These are the reasons for our enthusiasm about this report. Four achieved remission lasting less than 1 year. Splenectomy was performed to obtain a sustained remission in one patient following administration of three 2 mg doses of vincristine and two relapses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798157 TI - Goodpasture's syndrome in childhood: treatment with plasmapheresis and immunosuppression. AB - Goodpasture's syndrome rarely affects children. Therefore, we present our experience in a young boy whose pulmonary hemorrhage was dramatically resolved by three plasma exchanges. We believe the hemorrhage was caused primarily by acute capillaritis. He received cytoxan and steroids and a series of plasma exchanges which removed/suppressed his anti-glomerular basement membrane (anti-GBM) antibody production. However, after a year, his renal function did not return, and he required renal transplantation and continues to do well. PMID- 7798158 TI - Synchronization of plasma exchange and cyclophosphamide in severe and refractory autoimmune hemolytic anemia. AB - Two cases of severe autoimmune hemolytic anemia (AIHA) that failed multiple treatment modalities obtained complete and long-lasting remissions with a combination of three one volume plasma exchange (PE) on succeeding days followed 6 hours later on the 3rd day by cyclophosphamide (cyc) 750 mg/m2 IV, and cyc/prednisone (pred) qd tapering to either no therapy or minimal therapy over a 6 month period. Both cases remain without evidence of AIHA after 43 and 19 months follow-up. Possible non-exclusive mechanisms that explain this favorable outcome are enhanced cytotoxic effect of cyc on proliferating lymphocytes participating in the antibody rebound phenomena, suppression of B lymphocytes with daily cyc/pred, and/or formation of anti-idiotype antibodies. PMID- 7798155 TI - Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. AB - The cellular level and activity of the general amino acid permease, the product of the GAP1 gene of Saccharomyces cerevisiae, are regulated at the level of transcription by two systems, the products of URE2/GLN3 and NIL1 in response to the nitrogen sources of the growth medium and inactivation in response to the presence of glutamine or glutamate. Active permease is phosphorylated. The addition of glutamine causes rapid dephosphorylation and inactivation of the permease with the same kinetics, which is followed by slower disappearance of the protein. These results suggest that inactivation of the permease results from its dephosphorylation. PMID- 7798159 TI - Decrease of thyroid hormones in patients with familial hypercholesterolemia during dextran sulphate low-density lipoprotein apheresis. AB - Removal of low-density lipoproteins from plasma by dextran sulfate adsorption (DSA) in FH patients entails a decrease in plasma levels of thyroid hormones ( 28.5% and -18.7%, respectively, for T3 and T4). This suggests that FH patients have a greater than normal fraction of thyroid hormones bound to lipoproteins, due to their expanded lipoprotein pool. PMID- 7798160 TI - Integration of concurrent collection of plasma into a plateletpheresis program. AB - We have reviewed our initial experience with a program of concurrent collection of plasma (CCP) during plateletpheresis, which was instituted to increase the number of units of fresh frozen plasma produced by our hospital-based donor service. Sixty percent of eligible donors (1,006 of 1,682) participated in CCP, and 21 donors subsequently dropped out of the program. Of these, only one of four first-time donors have returned, whereas the majority of established plateletpheresis donors (16 of 17) have continued to donate platelets. Additional plasma was collected at a minimum of 8-week intervals on the Fenwal CS-3000 Plus or COBE Spectra without a change in the requirements for donor testing or the collection procedure. The quality of these platelet products was compared to that of those donated without CCP. There was a small decrease in platelet yield for products with CCP on the CS-3000 Plus (mean yield 4.5 x 10(11) with CCP versus 4.9 x 10(11) without CCP, P < .01). No negative effects were seen on the percentage of products with a minimum yield of 3 x 10(11) platelets or on leukocyte contamination. In addition, there was no difference in the rate of adverse donor reactions. During a 12-month interval, CCP provided 34% (3,798 of 11,266 units) of all fresh frozen plasma for our hospital without additional staff or equipment. The results of this retrospective study suggest that CCP merits further evaluation. PMID- 7798162 TI - Effects on recipients of exposure to allogeneic donor leukocytes. AB - Blood transfusion recipients are exposed to allogeneic donor leukocytes at the time of transfusion. Exposure to allogeneic donor leukocytes has been linked to a variety of complications of transfusion including primary HLA alloimmunization and platelet refractoriness, febrile nonhemolytic transfusion reactions, transmission of leukotropic viruses, transfusion-associated graft versus host disease, and transfusion-induced immune suppression. The development of high performance leukodepletion blood filters and of low-leukocyte plateletapheresis machines has provided the technology to reduce recipient exposure to allogeneic donor leukocytes. This article provides a brief review of current information on the utility and shortcomings of these technologies for the prevention of leukocyte-mediated transfusion complications. PMID- 7798163 TI - Cellular gene therapy: an overview. AB - Recombinant DNA technology has provided the tools for gene-based cellular therapies. The increasing ability to characterize disease in molecular terms affords the scientific rationale for gene therapy, while advances in cell biology, cytokine physiology, and gene delivery have made somatic cell gene therapy feasible. In 1990, the first successful human gene therapy was performed to correct severe combined immunodeficiency resulting from an inherited disorder, adenosine deaminase deficiency. Peripheral blood lymphocytes were used to deliver a gene product as temporary therapy. Today more than a dozen clinical protocols, using a variety of cell types and gene vectors, are in different stages of development. Some promise to be curative. Potential target illnesses include a variety of inherited genetic diseases, as well as such acquired disorders as cancer and AIDS. Although basic problems relating to gene transfer efficiency and expression, assay systems, and quality assurance remain, the technology to collect large numbers of cells, to purify cell subsets, to gene-modify these cells, and to expand them for human infusion suggest practical new strategies for cellular gene therapy. PMID- 7798161 TI - Effects on donors of repeated leukocyte losses during plateletpheresis. AB - All blood components collected by automated cytapheresis contain donor leukocytes. The possibility that repeated cytapheresis donation might lead to clinically important leukocyte losses and immunodeficiency has been a long standing concern. Although convincing data do not exist to substantiate this concern, it is common practice to limit the number of annual cytapheresis donations per donor and to monitor donors for developing lymphocytopenia. Clinically significant immunodeficiency is unlikely to occur unless donors lose > 1 x 10(11) lymphocytes within a few weeks period of time or unless donor lymphocyte counts fall persistently to < 0.5 x 10(9)/L. Each plateletpheresis procedure, when performed using modern cell separators that are designed to produce a relatively "pure" platelet concentrate, leads to the loss of 1.0 x 10(6) to 5.0 x 10(7) leukocytes. Thus, automated plateletpheresis as performed in 1994 is extremely unlikely to cause clinically significant lymphocyte depletion and consequent immunodeficiency. PMID- 7798165 TI - Manual plasmapheresis in the treatment of Guillain-Barre syndrome. AB - We report on 41 patients with Guillain-Barre Syndrome (GBS) with disability grade 4 and 5 who were treated with manual plasma exchange (PE). Approximately 20-40 ml/kg body weight of plasma was removed with each manual PE; 63% of patients needed one PE, 24% needed two, 10% needed three, and 2% needed four plasma exchanges. Normal saline, human serum albumin (NSA) and fresh frozen plasma were used in varying proportions as replacement solutions. Ninety-one percent of the patients resumed walking with very little assistance ranging from 4 to 56 days with an average of 25 days from the commencement of the first PE. Manual PE in our series was effective and safe as the reported experience of automated apheresis and less volume of plasma was exchanged in our patients undergoing manual PE when compared to those treated in other studies employing automated PE. PMID- 7798164 TI - Rapid red cell transfusion by apheresis. AB - Packed red cells (RBC) are customarily infused slowly to allow time for re equilibration of intravascular volume, but they may be given rapidly for convenience during hemodialysis or partial RBC exchange when blood volume can be adjusted extracorporeally. We describe an apheresis procedure for rapid transfusion of RBC to patients with chronic anemia in which an equivalent volume of recipient plasma is withdrawn as donor RBC are infused. Fifteen such procedures, transfusing 3 to 5 RBC units each, have been performed on nine patients (4 of them outpatients) with either COBE Spectra or COBE 2997. Mean +/- SD procedure duration was 1.79 +/- .44 hr; patient hemoglobin rose from 7.3 +/- 1.5 to 12.0 +/- 1.5 g/dl. Comparison to conventional transfusion was possible for nine procedures on six patients in which rapid transfusion required .52 +/- .12 vs. 2.70 +/- .37 hr per unit (P < .001) and raised hemoglobin by 1.22 +/- .30 vs .88 +/- .34 g/dl per unit (P < .02). Pink plasma noted during one procedure was attributable to infusion of an older AS-1 unit with extensive storage hemolysis. Rapid transfusion was subjectively well tolerated. Immediate post-procedure systolic blood pressures did not differ significantly from baseline, although one hypertensive patient had headache followed by increased blood pressure 4 hours after a procedure. We conclude that rapid transfusion of RBC is a technically feasible and more time efficient means for RBC transfusion. It is particularly attractive in the outpatient setting, and could also prevent fluid overload associated with RBC transfusion in some volume-sensitive patients. PMID- 7798166 TI - The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury. AB - Although mammalian xanthine oxidase exists originally as a dehydrogenase form in freshly prepared samples, it is converted to an oxidase form during purification, either irreversibly by proteolysis or reversibly by sulfhydryl oxidation of the protein molecule. However, avoiding proteolysis the mammalian enzyme can be purified as an interconvertible form and thus can be used to compare directly the properties of xanthine dehydrogenase and the oxidase derived from the same enzyme molecule. The cDNAs encoding the enzyme have been cloned from several sources, and structural information is becoming available. The most significant difference between the two forms is the protein conformation around FAD, which changes the redox potential of the flavin and the reactivity of FAD with the electron acceptors, NAD and molecular oxygen. The flavin semiquinone is thermodynamically stable in xanthine dehydrogenase, but is unstable in xanthine oxidase. Detailed analyses by stopped-flow techniques suggest that the flavin semiquinone reacts with oxygen to form superoxide anion while the fully reduced flavin reacts to form hydrogen peroxide. Although xanthine dehydrogenase can produce greater amounts of superoxide anion than xanthine oxidase during xanthine-oxygen turnover, it seems to be physiologically insignificant because NAD inhibits almost completely the formation of superoxide anion. Although the involvement of this enzyme in reperfusion injury has been proposed, this seems to be more complex than originally envisaged and still remains to be established. PMID- 7798167 TI - Energy metabolism of spermatozoa of the sand dollar Clypeaster japonicus: the endogenous substrate and ultrastructural correlates. AB - Energy metabolism in spermatozoa of the sand dollar-sea urchin Clypeaster japonicus was examined. The spermatozoa contained triglyceride and cholesterol ester besides several kinds of phospholipids and cholesterol. Glycogen and glucose were present at extremely low levels. Following incubation of spermatozoa in seawater, the triglyceride content decreased rapidly. Other lipids, however, remained at constant levels. High lipase activity was demonstrated in the spermatozoa. Also, [1-14C]oleic acid was oxidized to 14CO2. Ultrastructural study showed that lipid globules were present at the bottom of the midpiece. After incubation in seawater, morphological changes in the lipid globules were observed and vacuoles of various sizes appeared near the lipid globules. Thus, it is concluded that C. japonicus spermatozoa obtain energy through oxidation of fatty acid from triglyceride stored in the lipid globules at the midpieces. PMID- 7798169 TI - Calcium-dependent regulation of smooth muscle calponin by S100. AB - Calponin, a major calmodulin-, actin-, and tropomyosin-binding protein in smooth muscle, interacted with brain S100 and the properties of the interaction were investigated in detail. From fluorescence labeling and chemical cross-linking experiments, the apparent Kd value was calculated to be 7 x 10(7) M-1 in the presence of Ca2+ with 1 mol of S100 bound per mol of calponin. The addition of S100 to the mixture of calponin and F-actin caused the removal of calponin from actin filaments in the presence of Ca2+ but not in the presence of EGTA or Zn2+. Ca2+ and S100 could relieve calponin-induced actomyosin Mg(2+)-ATPase inhibition. Both the removal of calponin from F-actin and the restoration of ATPase inhibition by S100 were more effective than those by calmodulin. At low ionic strength, the binding was observed irrespective of Ca2+ concentration and it was greatly weakened with increasing salt concentration. The formation of the complex in the presence of Ca2+ was less sensitive, with only 45% inhibition at 100 mM NaCl, where the complex in the absence of Ca2+ had almost disappeared. This was confirmed by S-100 Sepharose 4B chromatography. Addition of Ca2+ and S100 also led to a decrease in the affinity of calponin for tropomyosin. Domain mapping with chymotryptic digestion revealed that the S100 binding site resided within the N-terminal 22 kDa fragment of calponin, where the bindings of calmodulin and actin also occur. PMID- 7798168 TI - Purification and amino- and carboxyl-terminal amino acid sequences of alanine glyoxylate transaminase 1 from human liver. AB - In order to confirm the amino acid sequence predicted from the nucleotide sequence of cDNA and also to elucidate the intracellular localization and molecular evolution, human liver alanine-glyoxylate transaminase 1 (AGT1) was purified and subjected to partial amino acid sequence determination, with special attention to posttranslational modification. The enzyme was purified to homogeneity from the 10,000 x g supernatant of human liver homogenate. The purified enzyme showed only a single protein band at about 43 kDa on SDS-PAGE, indicating that it is a homodimer of two identical subunits, because the native enzyme has a molecular mass of about 80 kDa. Both the amino- and carboxyl terminal peptides of the enzyme were isolated from a cyanogen bromide digest of the S-carboxyl-methylated protein and subjected to amino acid sequence determination. The alpha-amino group of the amino-terminal peptide was shown to be blocked by an acetyl group. The carboxyl-terminal sequence contained a putative N-glycosylation sequence (-Asn-Ala-Thr-), the only one present in the whole molecule, but this sequence was normally determined, indicating that the enzyme is not N-glycosylated. Purdue et al. [J. Cell Biol. 111, 2341-2351 (1990)] have reported that Pro-11, Gly-170, and Ile-340 in normal human AGT1 were replaced by Leu, Arg, and Met, respectively, in a patient with primary hyperoxaluria type 1. We confirmed that residue-11 was Pro. Both the amino- and carboxyl-terminal sequences of the enzyme showed extensive similarity with those of rat liver mitochondrial serine-pyruvate aminotransferase and the small chain of hydrogenase from a thermophilic unicellular cyanobacterium, Synechococcus PCC 6716.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798170 TI - A survey of genes expressed in undifferentiated mouse embryonal carcinoma F9 cells: characterization of low-abundance mRNAs. AB - As a first step to catalogue mRNAs present in mouse embryonal carcinoma F9 cells, 879 clones corresponding to low-abundance mRNAs were selected from among 2,896 randomly picked up clones of undifferentiated F9 cDNA libraries, using DNA probes complementary to poly(A)+RNAs prepared from undifferentiated F9 cells and to ones prepared from mouse fibroblast L cells. Five-hundred and eighty-two of the 879 clones were partially sequenced, and the subsequent homology search revealed that 201 corresponded to 180 known genes or known DNA sequences, which include not only housekeeping genes but also various tissue-specific genes. Interestingly, at least 24 of the 180 genes are development-related genes in mammals. Among these 24, those for midkine (growth and/or differentiation factor) and interferon-beta are reportedly up-regulated, and those for ECA39 (target for c-Myc regulation), REX-1 (zinc finger protein), and OCT-3 (POU-domain transcription factor) are down regulated during the development of mouse embryonal carcinoma cells. Thirty-seven of the 582 clones matched the 36 previously reported unidentified ESTs (expressed sequence tags) and the remaining 344 corresponded to 329 novel ESTs. Therefore, partial sequencing of F9 cDNA clones corresponding to low-abundance mRNAs in F9 cells not only provides valuable information concerning development-related genes in mammals, but also many novel ESTs useful for studying mammalian genomes. PMID- 7798172 TI - Preparation of separated alpha and beta subunits of electron-transferring flavoprotein in unfolded forms and their restoration to the native holoprotein form. AB - Electron-transferring flavoprotein (ETF) isolated from pig kidney is a heterodimer containing one FAD and one AMP [Sato, K. et al. (1993) J. Biochem. 114, 215-222]. This paper presents a method for separation of the alpha and beta subunits on a preparative scale. The subunits were separated by cation-exchange chromatography in the presence of 6 M urea at pH 7.6. The subunits were obtained in unfolded forms with denaturant. The unfolded subunits were restored to the heterodimeric form having FAD and AMP with high yield after incubation with FAD and AMP under non-denaturing conditions. The far-UV CD spectrum, the fluorescence and absorption spectra of the bound FAD, and the enzyme activity of the reconstituted ETF were all identical to those of the ETF isolated from pig kidney. Thus, an experimental system was established for the reconstitution of ETF from the four components, alpha, beta, FAD, and AMP. Analyses of the absorption spectra of the separated subunits suggested that the contents of aromatic residues were one tryptophan and six tyrosines in alpha and one tryptophan and one tyrosine in beta. The possibility that one subunit binds with FAD or AMP in the absence of the other subunit was examined by measuring the flavin and protein fluorescence spectra, but no spectral changes reflecting such binding were detected. This result suggests that the coexistence of both the subunits is necessary for the binding of FAD and AMP with the protein. PMID- 7798171 TI - Effect of brefeldin A on ganglioside metabolism in cultured neurons: implications for the intracellular traffic of gangliosides. AB - The effect of BFA on the metabolic processing and intracellular traffic of gangliosides was studied in cerebellar granule cells, fed in culture for different periods with radiolabeled ganglioside GM1. The following results were obtained: (a) degradation of taken-up GM1 was markedly inhibited by BFA; this effect was rapid, reversible, and affected by reduced temperature, ATP depletion, and microtubule disruption: (b) direct glycosylation of internalized GM1 to GD1a was completely blocked by BFA; (c) the portion of GM1 that escaped BFA inhibition was degraded with formation of sphingosine, that was recycled for the biosynthesis of less glycosylated glycolipids (glucosyl-ceramide, GM3 and GD3); (d) in BFA-treated cells highly glycosylated gangliosides were undetectable, and the formation of sphingomyelin from liberated sphingosine was markedly reduced. These results suggest that, in the cells used: (a) the delivery of endocytosed gangliosides to lysosomes, (b) the flow of poorly glycosylated glycolipids from the Golgi stacks to the trans-Golgi network, and (c) the direct transport of part of endocytosed gangliosides to the late sites of glycosylation (possibly TGN) are mediated by BFA-sensitive vesicles. We propose that in cultured granule cells a BFA-sensitive mechanism regulates ganglioside traffic to and from the plasma membrane. PMID- 7798173 TI - Reconstitution of import-competent outer membrane vesicles from mammalian mitochondria. AB - Protein insertion into mitochondrial outer membrane (OM) vesicles isolated from Neurospora crassa has recently been reported. The N. crassa OM vesicles retained the features of the intact mitochondria concerning the dependency of insertion on the receptor protein [A. Mayer et al. (1993) J. Cell Biol. 121, 1233-1243]. In this study, OM vesicles were purified from bovine adrenal cortex mitochondria, and unilamellar proteoliposomes were reconstituted from OM vesicles using heptyl beta-thioglucoside. Both OM vesicles and the reconstituted outer membrane vesicles (ROM) were able to import porin, but unable to import the precursor of adrenodoxin, which translocates across both the outer and inner membranes of intact mitochondria. Porin insertion into both OM vesicles and ROM was inhibited in the presence of purified recombinant adrenodoxin precursor and also by ATP depletion, and was dependent on the trypsin-sensitive membrane surface factor, suggesting that the purified OM vesicles as well as ROM retained the properties of the intact OM concerning porin insertion. The protein import machinery of OM seems to be functional for the outer membrane protein without the participation of the inner membrane. The successful reconstitution of the protein import activity from solubilized OM will pave the way for further biochemical characterization of the protein import machinery of OM. PMID- 7798174 TI - The transmembrane region of microsomal cytochrome P450 identified as the endoplasmic reticulum retention signal. AB - Microsomal-type cytochrome P450s are integral membrane proteins bound to the membrane through their N-terminal transmembrane hydrophobic segment, the signal anchor sequence. To elucidate the determinants that enable the P450s to be located in the ER, we constructed cDNAs encoding chimeric proteins in which a secretory form of carboxyesterase, carboxyesterase Sec, was connected to the N terminus of the full-length or truncated forms of a microsomal-type P450, P450(M1), and the constructed plasmids were expressed in COS cells. Since carboxyesterase Sec is an N-glycosylated secretory protein, endo H treatment could be used to determine whether these chimeric proteins were located in the ER or not. Carboxyesterase Sec with the N-terminal 20 amino acids, containing the transmembrane region, of P450(M1), was located in the ER, as determined from the endo H sensitivity of the expressed protein and immunofluorescence staining of the cells. As the expressed protein exhibited carboxyesterase activity, it was not retained in the ER through the BiP-dependent quality control system recognizing unfolded proteins. Another chimeric protein construct in which carboxyesterase Sec was connected to the C-terminal region of rat UDP glucuronosyltransferase (UDP-GT), that contained a double-lysin ER retention motif, was also located in the ER, as determined from the endo H sensitivity and immunofluorescence staining. On the other hand, the sugar moiety of the carboxyesterase Sec connected to the transmembrane segment of UDP-GT, Sec/GTd, was partially resistant to the endo H treatment. From the results of immunofluorescent staining and cell fractionation, it was concluded that the Sec/GTd product was located in the Golgi apparatus. These observations indicated that the N-terminal hydrophobic segment of P450(M1) is sufficient for the ER membrane retention, whereas the transmembrane segment of UDP-GT is not. To determine whether microsomal P450s are recycled between the ER and Golgi compartments or not, a DNA construct encoding cathepsin D connected to the N terminus of P450(M1) was prepared and expressed in COS cells. The fusion protein was phosphorylated, but the phosphorylation was sensitive to alkaline phosphatase. As a control, authentic cathepsin D was subjected to phosphorylation of its oligosaccharide chain that was resistant to the alkaline phosphatase treatment. Since GlcNAc-P-transferase, which forms the alkaline phosphatase resistant phosphodiester in the sugar chains of lysosome-targeting proteins, is located in the Golgi apparatus, it was concluded that the oligosaccharide chain of the cathepsin D portion of the fusion protein was not phosphorylated, and that the chimeric protein did not go to the Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798175 TI - Role of the conserved glycyl residues located at the active site of leucine dehydrogenase from Bacillus stearothermophilus. AB - A tetrapeptide sequence, Gly-Gly-(Gly/Ala)-Lys, containing a catalytically important lysyl residue, is highly conserved in NAD(P)+-dependent amino acid dehydrogenases. To elucidate functional roles of the glycyl residues in this conserved sequence Gly-77, Gly-78, and Gly-79 of the recombinant leucine dehydrogenase from Bacillus stearothermophilus have been individually replaced with Ala by site-directed mutagenesis. All of the mutant enzymes had Michaelis constants for alpha-keto-iso-caproate and ammonia several times larger than the wild-type enzyme while retaining considerable catalytic activities. However, inhibition constants for a substrate analog without an alpha-carbonyl group were unchanged by the mutations. On the other hand, the rate of inactivation by pyridoxal 5'-phosphate and the microenvironment of aromatic residues, in particular of the sole tryptophanyl residue (Trp-46) located in the vicinity of the active site, were affected by the mutations of the glycyl residues. All of these results suggest that the conserved glycyl residues are important for fine tuning of the position and/or orientation of the epsilon-amino group of Lys-80 at the active site to function efficiently as a general-base catalyst. Furthermore, the Gly-77 and Gly-78 mutant enzymes had markedly decreased thermal stabilities, showing that these two glycyl residues are also critical for the conformational stability of this thermostable enzyme. PMID- 7798176 TI - Studies on an artificial trypsin inhibitor peptide derived from the mung bean trypsin inhibitor: chemical synthesis, refolding, and crystallographic analysis of its complex with trypsin. AB - The active fragment with Lys at the reactive site of mung bean trypsin inhibitor (MBILF) is composed of two peptide chains, A1 of 26 residues and A2 of 9 residues linked via two disulfide bonds. In the present study, a peptide of 22 residue comprising the sequence of chain A1 from position 3 to 24 was synthesized by the solid-phase method. This synthetic peptide with six Cys residues contains a reactive site at position Lys11I-Ser12I (I denotes an inhibitor residue). Air oxidation and HPLC purification resulted in two antitrypsin active components, SPC1 and SPC2. Neither SPC1 nor SPC2 can stoichiometrically inhibit trypsin. The Ki values of SPC1 and SPC2 are 1.2 x 10(-7) and 4.0 x 10(-8) M, respectively. The complexes of SPC1 and SPC2 with bovine beta-trypsin (BTRY) were crystallized by ammonium sulphate precipitation at pH 6.4 and 6.0, respectively. The two crystals have the same crystal form with space group P2(1)2(1)2(1) and cell dimension of a = 63.2(2) A, b = 63.5(6) A, and c = 69.8(4) A. The crystal structure of one complex, SPC1-BTRY, was determined and refined at 2.2 A resolution to a final R value of 19.2%. From the resulting electron density map, 9 residues of SPC1, from position 9I to 17I, were identified clearly and three-dimension atomic model of the 9-residue reactive loop formed by a disulfide bridge, Cys9I-Cys17I, was built. No electron density corresponding to the other 13 residues was observed in the present map.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798177 TI - Characterization of glycophorin A transcripts: control by the common erythroid specific promoter and alternative usage of different polyadenylation signals. AB - Glycophorins A (GPA) and B (GPB) are specifically expressed in human erythrocytes and express MN and Ss blood group antigens. While the GPB gene produces one transcript, the GPA gene produces three or four transcripts of different sizes. To understand the mechanisms of production of the different transcripts and erythroid-specific expression, we characterized the transcripts and the transcriptional regulatory regions of the glycophorin A gene. The transcriptional start site was determined by primer extension and S1 nuclease protection analysis, and it was found that all of the transcripts start at one major site. The nucleotide sequence of the newly isolated longest GPA cDNA revealed several polyadenylation signal sequences. To determine which polyadenylation signals are utilized, cDNA clones encoding GPA were isolated from a cDNA library of human erythroleukemia cell line K562 and the 3'-regions of the cDNAs were specifically amplified by the polymerase chain reaction. These results showed that five different polyadenylation signals of the GPA gene are utilized and the size and abundance of the transcripts are consistent with those detected by Northern blot analysis of K562 mRNAs. The 5'-flanking sequence was found to contain several binding motifs for the transcription factors, which were also found in other erythroid-specific genes. These motifs include the binding sites for the GATA-1 and NF-E2 erythroid-specific transcription factors, in addition to Sp1 transcription factor. The 5'-sequence from -750 to +36 relative to the transcriptional start site could confer only a low basal transcriptional activity in K562 cells and Friend erythroleukemia cells. This activity was significantly increased after Friend erythroleukemia cells were differentiated by dimethylsulfoxide. These results suggest that the 5' region regulates the glycophorin gene expression in erythroid-specific fashion. PMID- 7798178 TI - Contribution of Ad4BP, a steroidogenic cell-specific transcription factor, to regulation of the human CYP11A and bovine CYP11B genes through their distal promoters. AB - We analyzed the upstream regions of the human CYP11A and bovine CYP11B genes, and identified a distal promoter in each gene. The distal promoters are located at 1.8 to -1.5 kb in the upstream region of the CYP11A gene and -1.5 to -1.1 kb in the upstream region of the CYP11B gene. Transient transfection of CAT plasmid carrying each of the two distal promoters indicated that the regions had a transcriptional activating function and that the function was stimulated by cAMP. The basal and cAMP-stimulated transcriptional activities were detected only in steroidogenic cells. On structural analyses of the regions, we identified two Ad4 sites and a cAMP responsive element in the distal promoter of CYP11A, and two Ad4 sites and one NF-IL6 binding site in the distal promoter of CYP11B. The presence of an Ad4 site in common suggests its major contribution of the transcriptional activation. We also investigated the functional interactions between the distal promoters and basal promoters of both genes. Interestingly, the two distal promoters showed different requirements as to the basal promoter. PMID- 7798179 TI - Purification and characterization of four Ca(2+)-dependent lectins from the marine invertebrate, Cucumaria echinata. AB - Four Ca(2+)-dependent, N-acetylgalactosamine/galactose-specific lectins were purified from the marine invertebrate, Cucumaria echinata (Holothuroidea), by column chromatography on lactosyl-Sepharose 4B, Sephacryl S-200, and Q-Sepharose. The molecular masses of these lectins were estimated to be 27 kDa (CEL-I), 35 kDa (CEL-II), 45 kDa (CEL-III), and 68 kDa (CEL-IV) on SDS-PAGE under nonreducing conditions. Among these lectins, CEL-I and CEL-IV strongly agglutinated rabbit and human erythrocytes, and were found to recognize N-acetylgalactosamine and galactose-containing carbohydrates from the results of a hemagglutination inhibition assay. In contrast, CEL-II failed to agglutinate any erythrocytes tested, although its carbohydrate-binding ability was confirmed by a carbohydrate binding assay involving asialofetuin-horseradish peroxidase. Interestingly, CEL III caused hemolysis of rabbit and human erythrocytes, while it showed only hemagglutination of chicken and horse erythrocytes at relatively high concentrations. The hemolytic activity of CEL-III was also dependent on the Ca(2+)-concentration, and inhibited by N-acetylgalactosamine and galactose containing carbohydrates, suggesting that the hemolysis was caused by Ca(2+) dependent binding of CEL-III to specific carbohydrate chains on the erythrocyte surface and the following partial destruction of the membrane. PMID- 7798180 TI - Morphological and physicochemical changes in the myosin molecules induced by hydrostatic pressure. AB - Hydrostatic pressure-induced morphological and physiochemical changes in monomeric myosin were investigated. The turbidity of a myosin solution increased after release of pressure, indicating aggregation of the molecules. Some molecules were single headed after exposure to 100-200 MPa, in contrast with an intact molecule having two heads. Small-sized oligomeric species, composed of several molecules, appeared after pressurization at 200 MPa. The oligomers were formed only through head-to-head association. Neither head-to-tail nor tail-to tail interaction was observed. With increasing pressure to 300 MPa, monomeric myosin remarkably decreased, and most molecules formed oligomers, in which the myosin heads were tightly associated, forming a clump, the tails of the myosin molecules extending radially from the clump. Such an oligomer was shaped like a daisy wheel and its morphology was quite similar to that formed on heating reported previously [Yamamoto et al. (1990) J. Biochem. 108, 896-898]. The aggregation of myosin molecules upon pressurization was concomitant with an increase in hydrophobicity, which was measured spectrofluorometrically with 8 anilino-1-naphthalene sulfonate, a probe for apolar binding sites. Although the turbidity increased continuously with increasing pressure, the hydrophobicity remained at a constant level above 200 MPa at pH 6.0 and above 300 MPa at pH 7.0. The loss of myosin ATPase activity was accompanied by aggregation of the molecules. These results indicate that hydrophobic groups in the heads of myosin are exposed to the surface of the molecule on pressurization, so that hydrophobic interaction among the heads occurs, yielding aggregates. Beside the hydrophobic interaction, the contribution of other interaction(s) is also suggested. PMID- 7798181 TI - Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria. AB - Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle, and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms. In this study, homology probing with mixed primers for the polymerase chain reaction and subsequent sequence analysis were successfully applied to clone cDNA for the flavoprotein (Fp) subunit of human liver complex II. The isolated clone contains an open reading frame of 1,992 nucleotides and encodes a mature protein of 621 amino acids with a molecular weight of 68,011. The amino acid sequence was highly homologous with that of bovine heart Fp (93.2%) and was quite different from the partial sequence of human placental Fp reported previously [Malcovati et al. (1991) in Flavins and Flavoproteins 1990, pp. 727-730], which showed striking homology to that of Bacillus subtilis. To solve this discrepancy, the partial cDNA sequences of the stomach and placental Fp subunits of human complex II were determined in addition to the full length cDNA of liver. The sequence data, sensitivity to thiol reagents and antigenic properties indicated that the major from of FP subunit in human complex II is unique at least among the three tissues analyzed, and is more similar to the Fp subunit of bovine heart than to that of B. subtilis. PMID- 7798182 TI - Purification and primary structure of a new guanylic acid specific ribonuclease from Pleurotus ostreatus. AB - A guanine nucleotide-specific RNase (RNase Po1) was isolated from caps of the fruit bodies of Pleurotus ostreatus. RNase Po1 is most active towards RNA at pH 8.0. The effect of heating on the molar ellipticity at 210 nm of RNase Po1 showed that RNase Po1 is more stable than RNase T1. The primary structure of RNase Po1 was determined to be < ETGVRSCNCAGRSFTGTDVTNAIRSARAGGSGNYPHVYNNFEGFSFSCTPTFFEFPVFRGSVYSGGSPG ADRVIYD- QSGRFCACLTHTGAPSTNGFVECRF. It consisted of 101 amino acid residues, with a molecular weight of 10,760. RNase Po1 has relatively higher sequence homology with RNase T1 family RNase. It contains 6 half cystine residues. The locations of four of them are superimposable on those of RNase U1 and RNase U2. The amino acid residues forming the active site of RNase T1 were well conserved in this RNase. Therefore, RNase Po1 is a unique member of the RNase T1 family in respect of the location of one disulfide bridge, and its stability. PMID- 7798183 TI - Point mutations at glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function. AB - To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in a flexible loop (residues 117-131), separated by 19 A from active site Asp27, was substituted by site-directed mutagenesis with eight amino acids (Ala, Val, Leu, Asp, Ser, Cys, Tyr, and His). The free energy change of unfolding decreased in the order of G121A > G121D > G121C > G121S, wild-type > G121H > G121Y > G121L > G121V. The thermal denaturation temperature decreased with all mutations, accompanied by a decrease in the calorimetric enthalpy of denaturation. The steady-state kinetic parameter for the enzyme reaction, Km, was only slightly influenced, but kcat was significantly decreased by the mutations, there being 3- (G121C) to 42-fold (G121L) decreases in kcat/Km compared to that of the wild-type enzyme. The effects of mutations on the stability and enzyme activity were statistically examined as a function of the hydrophobicity and volume of amino acids introduced. The diminished stability and activity with increases in the hydrophobicity and volume of amino acids suggest that the main effect of the mutations would be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of the hydrophobic interaction. PMID- 7798185 TI - Sequence requirements for endoproteolytic processing of precursor proteins by furin: transfection and in vitro experiments. AB - We have recently presented some sequence rules that govern the endoproteolytic processing of precursor proteins within the constitutive secretory pathway [Watanabe, T. et al. (1992) J. Biol. Chem. 267, 8270-8274; Watanabe, T. et al. (1993) FEBS Lett. 320, 215-218]. This cleavage seems to be catalyzed by furin, a mammalian homologue of the yeast processing endoprotease Kex2. In this study, not only by coexpression of furin and substrate precursors in a furin-deficient cell line but also by in vitro experiments using purified recombinant furin and substrate precursors, we determined the substrate specificity of furin. The sequence requirements of furin determined by the coexpression and in vitro experiments were essentially the same, and were consistent with the sequence rules for precursor cleavage within the constitutive secretory pathway. PMID- 7798184 TI - Possible differences in the regenerative roles played by thioltransferase and thioredoxin for oxidatively damaged proteins. AB - A possible involvement of thioltransferase (also known as glutaredoxin) in the regenerative reaction of proteins inactivated by oxidative stress were examined in vitro using the enzyme purified from bovine liver. Thioltransferase at physiological concentrations, together with glutathione, glutathione reductase and NADPH, regenerated the oxidatively damaged proteins with a comparable potency to that of thioredoxin. Experiments performed with protein substrates with their critical cysteine residues oxidized differently, that is, phosphofruktokinase and glyceraldehyde 3-phosphate dehydrogenase with mixed disulfide bonds and glyceraldehyde 3-phosphate dehydrogenase with sulfenyl or sulfinyl groups, indicated that thioltransferase regenerated the proteins inactivated by mixed disulfide formation more efficiently than thioredoxin, whereas thioredoxin preferentially regenerated the proteins inactivated by monothiol oxidation to sulfenic or sulfinic acid. These findings suggested that thioltransferase exerted regenerative effects on oxidatively damaged proteins like its cognate protein, thioredoxin, but with different substrate specificity, and their relative contribution to the regeneration reaction is dependent on the form of the oxidized thiols of the damaged proteins. PMID- 7798186 TI - Purification and molecular cloning of cDNA for an inducible antibacterial protein from larvae of the coleopteran, Tenebrio molitor. AB - Antibacterial activity was induced in the hemolymph of larvae of the coleopteran Tenebrio molitor by injection of Escherichia coli. An antibacterial protein, named tenecin 1, was purified to homogeneity from the larval hemolymph and characterized. A cDNA clone for tenecin 1 was isolated and its complete sequence was determined. This protein was found to inhibit the growth of Gram-positive bacteria and to consist of 43-amino acid residues including six cysteine residues. The disulfide structure of tenecin 1 was determined by sequencing cysteine containing peptides obtained by digesting tenecin 1 with endopeptidase Lys-C, trypsin, and thermolysin. The amino acid sequence and its disulfide bonds were similar to those of sapecin and sapecin C, antibacterial proteins of Sarcophaga peregrina. PMID- 7798187 TI - Demonstration of high-molecular-weight kininogen in kininogen-deficient rat kidneys. AB - Brown Norway Katholiek (B/N-Ka) is a mutant rat strain deficient in plasma high molecular-weight (HK) and low-molecular-weight kininogen (LK). It has been reported that the deficiency, caused by defective secretion of HK and LK by the liver, is associated with a point mutation of alanine (163) to threonine in the common heavy chain. In this report we demonstrate by specific radioimmunoassay that the amount of immunoreactive HK antigen in the B/N-Ka kidney was almost the same as that found in the normal Brown Norway rat (Brown Norway Kitasato, B/N Ki). HK antigen in the kidneys of both strains was immunohistochemically localized at distal tubules with similar intensity in both strains. Among the subcellular fractions of the kidney homogenates, HK antigen was predominantly found in the microsomal fraction of both strains. To see whether this HK antigen is derived from plasma HK or is synthesized in the kidneys, we examined uptake of HK by the tubular cells after incubation with 125I-HK. Only 0.6% of the radioactivity of added 125I-HK was found in the tubular cells of both strains after a 60-min incubation. Messages of HK mRNA from both strains of rats were visualized by PCR at almost the same intensity. These results suggest that HK antigen found in the kidney may be derived mainly from biosynthesis in the kidney itself and partly from uptake of HK from blood. There was no difference in these features of HK between the kidneys of the deficient and the normal B/N rats. PMID- 7798188 TI - Substrate specificity and subsite affinities of rabbit liver acid alpha glucosidase. AB - The substrate specificity of rabbit liver acid alpha-glucosidase was investigated. The enzyme showed a wide specificity for various substrates, and hydrolyzed alpha-glucans such as glycogen and soluble starch. The k0 values (s-1) for maltose, kojibiose, nigerose, isomaltose, phenyl alpha-glucoside, panose, phenyl alpha-maltoside, soluble starch, beta-limit dextrin, amylopectin, shellfish glycogen, and rabbit liver glycogen were estimated to be 94.8, 18.8, 143, 3.6, 11.8, 27.8, 115, 99.2, 155, 83.5, 126, and 108, and the Km values (concentration of non-reducing terminal) for these substrates were 2.1, 1.8, 7.5, 36, 5.4, 1.9, 1.2, 0.90, 9.1, 1.0, 16, and 13 mM, respectively. Isomaltose and phenyl alpha-glucoside were unfavorable as substrates. The acid alpha-glucosidase is characterized by a relatively high activity toward glycogen. The k0 values (s 1) for maltotriose, -tetraose, -pentaose, -hexaose, -heptaose, and -octaose, and maltodextrin (n = 17) were 140, 140, 131, 132, 134, 132, and 74.3, and the Km values, 2.1, 1.8, 1.9, 3.4, 5.0, 4.9, 4.9 and 2.6 mM, respectively. Based on the rate parameters for the series of maltooligosaccharides, the subsite affinities (Ais) in the active site were evaluated as 0.54 (A1), 5.34 (A2), and 0.34 (A3) kcal/mol for subsites 1, 2, and 3, respectively. These three subsites were considered to be predominantly responsible for the binding of substrates to the active site. PMID- 7798189 TI - Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase. AB - Laurate omega-hydroxylase activity of human liver microsomes was strongly inhibited by an antibody against rabbit fatty acid omega-hydroxylase P450 4A5, and Western blot analysis with this antibody showed the presence of two immunochemically related proteins with apparent molecular weights of approximately 50 and 52 kDa in all of 14 human liver specimens examined. A fatty acid omega-hydroxylase (designated P450HL omega) was purified to a specific content of 15 nmol of P450/mg of protein from microsomes of a single human liver on the basis of its laurate omega-hydroxylase activity and its reactivity with the P450 4A5 antibody. This P450HL omega showed an apparent molecular weight of 52 kDa on SDS-PAGE. Furthermore, a cDNA clone (designated HL24) has been isolated from a human liver cDNA library by using the cDNA for P450 4A5 as a probe. The sequence of residues 5 through 25 deduced from cDNA HL24 was identical to the NH2 terminal amino acid sequence of P450HL omega except for one undetermined residue. This cDNA encoded a protein of 519 amino acids with a molecular weight of 59,347. The amino acid sequence predicted from the cDNA showed 82% identity with that of P450 4A5. Northern blot analysis showed that the mRNA hybridized to the cDNA is expressed in the human liver and kidney. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798190 TI - Preparation and characterization of human rheumatoid arthritic synovial fluid phospholipase A2 produced by recombinant baculovirus-infected insect cells. AB - We prepared human rheumatoid arthritic synovial fluid phospholipase A2 (PLA2) [EC 3.1.1.4] from insect cells infected with a recombinant baculovirus. The PLA2 DNA was designed, changing the original codons to those used frequently in the polyhedrin gene. Sixteen oligo-deoxynucleotides ranging from 40 to 70 nucleotides were chemically synthesized and then assembled to form the whole PLA2 gene. The gene thus synthesized was then placed under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus. The recombinant virus was infected into Spodoptera frugiperda cells. The infected cells secreted protein having PLA2 activity into the culture medium. The enzyme level in the medium reached about 3 mg/liter on day 4 after infection. The secreted protein was purified to a single band of 14,000 Da on SDS-PAGE, by means of cation exchange chromatography and reverse-phase HPLC. N-terminal amino acid sequence analysis revealed that the recombinant protein was recognized and cleaved at the signal sequence in the insect cell. The purified enzyme had almost the same specific enzyme activity, substrate specificity, pH optimum, Ca2+ ion dependency, and kinetic values as those of the natural enzyme. PMID- 7798191 TI - Nitric oxide reductase cytochrome P-450 gene, CYP 55, of the fungus Fusarium oxysporum containing a potential binding-site for FNR, the transcription factor involved in the regulation of anaerobic growth of Escherichia coli. AB - A unique cytochrome P-450 (P-450) is involved in fungal denitrification, acting as a nitric oxide reductase. The phylogenetic classification of the P-450 (P 450nor) into the group of bacterial P-450s along with its involvement in the anaerobic process are of evolutional interest. The corresponding gene, CYP 55, of the fungus Fusarium oxysporum was isolated and sequenced. The P-450nor gene contained 7 introns that consisted of 49 to 55 bp. The presence of the introns suggested that horizontal transfer of the gene from bacteria to the fungus, if it has occurred, was an early event in evolution. Besides a TATA box, several inverted repeats were found in the 5'-upstream flanking region. One inverted repeat exhibited the same sequence as the binding site of FNR (fumarate and nitrate reduction), a DNA-binding, O2 (dioxygen)-sensor protein that positively regulates expressions of many hypoxic genes in Escherichia coli and other bacteria. The result suggested that the expression of P450nor is regulated in response to oxygen tension by an FNR-like system. Northern blot analyses showed that both nitrate and nitrite are the actual inducers of P-450nor and that its expression is predominantly regulated at the transcriptional level. These results raise the interesting possibility that the expression of the fungal denitrification system is regulated, as in the case of bacterial nitrate respiration, by a set of mechanisms, i.e., a combination of an FNR-like system and a system responding to nitrate/nitrite. PMID- 7798192 TI - X-ray crystallographic study of pyridoxal 5'-phosphate-type aspartate aminotransferases from Escherichia coli in open and closed form. AB - We determined the three-dimensional structures of aspartate aminotransferase (AspAT) from Escherichia coli and its complex with inhibitor (2-methyl-L aspartate) at 1.8A resolution. This enzyme reversibly catalyzes the transamination reaction and is a dimer of two identical subunits. Each subunit has 396 amino acid residues and one pyridoxal 5'-phosphate as a cofactor, and is divided into two domains, one large and the other small. Upon binding of the inhibitor, the small domain rotates by 5 degrees toward the large domain to close the active site. This domain movement is caused mainly by small but important main-chain conformational changes in the residues located over the domain interface of the small domain. In chicken mitochondrial AspAT, the domain movement was larger, with a rotational angle of 13 degrees. By comparison of these two structures, the difference in the rotational angles was found to be caused by the larger opening of the domain in the open form of chicken mitochondrial AspAT. Although the overall structures of these two enzymes were almost identical, the surface area of the domain interface in the E. coli enzyme was larger than that in mitochondrial AspAT, suggesting that the structure of the domain interface is responsible for the degree of movement of the small domain. PMID- 7798193 TI - Platelet-derived growth factor receptor signals. PMID- 7798194 TI - A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors. AB - Shc is a ubiquitously expressed Src homology 2 (SH2) domain protein that can transform fibroblasts and differentiate PC12 cells in a Ras-dependent fashion. Shc binds a variety of tyrosine-phosphorylated growth factor receptors presumably via its carboxyl-terminal SH2 domain. We cloned a fragment of Shc when screening a bacterial expression library with tyrosine-phosphorylated epidermal growth factor (EGF) receptor. Surprisingly, this fragment encodes the amino terminus of Shc, a region that has no significant similarity to an SH2 domain. When expressed as a glutathione S-transferase fusion protein, this amino-terminal domain binds to autophosphorylated EGF receptor, as well as HER2/neu and TrkA receptors. This fragment acts like an SH2 domain in that it does not bind non-phosphorylated EGF receptor or EGF receptor with all tyrosine phosphorylation sites mutated or deleted. Our data define a novel domain in Shc that has the potential to interact with growth factor receptors and other tyrosine-phosphorylated proteins. PMID- 7798195 TI - Identification of the major chromaffin granule-binding protein, chromobindin A, as the cytosolic chaperonin CCT (chaperonin containing TCP-1). AB - Chromobindin A is a multisubunit complex ATPase that binds to chromaffin granule membranes in a calcium-dependent manner and requires ATP for release from the membrane (Martin, W. H., and Creutz, C. E. (1987) J. Biol. Chem. 262, 2803-2810). Here we report that the seven previously characterized subunits of chromobindin A cross react with antisera specific to subunits of CCT, the chaperonin containing TCP-1 (Kubota, H., Hynes, G., Carne, A., Ashworth, A., and Willison, K. (1994) Curr. Biol. 4, 89-99). The chromobindin A subunits previously called chromobindins 12, 13, 14, 15, 16, 18, and 19 cross-react specifically with subunits beta, delta, theta, alpha, zeta, xi, and gamma, respectively, of CCT. Additional similarities in subunit molecular weights, isoelectric points, and the morphologies of the two protein complexes as determined by electron microscopy support identification of chromobindin A as an adrenal medullary form of CCT. The chromobindin A/CCT complex was found to bind at least 7-fold more efficiently to affinity columns of chromaffin granule membranes than of adrenal medullary cytosol proteins, suggesting a specific interaction occurs between the complex and membrane components. The results indicate that the previously described characteristics of chromobindin A are likely to be relevant to the functions of CCT and suggest that the adrenal medullary form of CCT may play a role in the activities of secretory vesicle membranes. PMID- 7798196 TI - Evidence of a self-catalytic mechanism of 2,4,5-trihydroxyphenylalanine quinone biogenesis in yeast copper amine oxidase. AB - Copper amine oxidases are representative of a new class of redox enzymes that contain a peptide-bound quinone cofactor, generated by posttranslational modification of amino acid side chain(s). We have investigated the mechanism for the biogenesis of 2,4,5-trihydroxyphenylalanine quinone (TPQ) in amine oxidase with two site-specific mutants of the yeast methylamine oxidase. Our results show that the capacity for TPQ formation in vivo is abolished when a putative ligand to copper, His-456, is changed to Asp; this H456D mutant binds copper at a low level (approximately 4.1%), relative to the wild-type protein. In contrast, altering the active site consensus sequence that contains the precursor tyrosine does not affect TPQ production. The data implicate a self-catalysis mechanism for TPQ biogenesis, in which the protein-bound copper plays a key role. We propose that the minimal information required for TPQ biogenesis lies in a structural motif consisting of the copper site and the precursor tyrosine. PMID- 7798197 TI - The cytotoxic T cell proteinase granzyme B does not activate interleukin-1 beta converting enzyme. AB - Murine granzyme B (cytotoxic cell proteinase-1 (CCP1)) is a member of a family of seven serine proteases found in cytoplasmic granules of cytotoxic T lymphocytes (CTLs). Evidence has suggested that it is involved in target cell DNA fragmentation during CTL-mediated cytotoxicity, although intracellular substrates for granzyme B have not yet been identified. The substrate specificity of granzyme B, requiring an aspartic acid residue at site P1, is unique among eukaryotic serine proteases and is shared with only one other known eukaryotic protease, interleukin-1 beta-converting enzyme (ICE). ICE is responsible for processing pro-interleukin-1 beta to produce biologically active interleukin-1 beta and is itself synthesized as an inactive precursor. Recent evidence has suggested a role for ICE in programmed cell death, which led to a model for CTL mediated cytotoxicity. In this proposal granzyme B activates ICE in the target cell by proteolytically processing the ICE precursor, resulting in active ICE heterodimer that induces apoptosis in the target cell. We have isolated the cDNA encoding murine ICE and generated in vitro translated ICE precursor. Using lysates from COS cells expressing granzyme B we show that ICE precursor is not a substrate for granzyme B and propose an alternate mechanism for CTL-mediated cytotoxicity. PMID- 7798198 TI - Depletion of intracellular Ca2+ stores activates a maitotoxin-sensitive nonselective cationic current in beta-cells. AB - Glucose stimulation of beta-cell insulin secretion is initiated by membrane depolarization coupled with an elevation in intracellular Ca2+ concentration ([Ca2+]i). Both depolarization-dependent Ca2+ entry and intracellular Ca2+ store release contribute to the sugar-induced rise in [Ca2+]i. Here we show that maneuvers depleting intracellular Ca2+ stores induce membrane depolarization and a sustained nitrendipine-sensitive Ca2+ influx, whereas interventions promoting Ca2+ store refilling produce a hyperpolarization and inhibit Ca2+ influx. Both intracellular Ca2+ store depletion and maitotoxin activated a depolarizing nonselective cation current carried principally by Na+ in the physiological range of membrane potentials. The activation of such a current may form the paradigm by which excitable cells refill depleted intracellular Ca2+ stores by depolarization driven opening of voltage-activated Ca2+ channels. PMID- 7798199 TI - A helical element in the C-terminal domain of the N. plumbaginifolia F1 beta presequence is important for recognition by the mitochondrial processing peptidase. AB - The mitochondrial processing peptidase (MPP) in lower eucaryots and mammals is a matrix enzyme, whereas MPP in plants constitutes an integral part of the bc1 complex of the respiratory chain. The isolated spinach leaf bc1 complex catalyzes cleavage of the precursor of Nicotiana plumbaginifolia F1 beta subunit of the ATP synthase, resulting in a production of mature protein and a presequence that consists of 54 amino acids. A synthetic peptide derived from the C-terminal part of the presequence, containing 17 amino acids with a helical structural element, p-F1 beta(38-54), was an efficient inhibitor of the processing, whereas a peptide derived from the N-terminal part of the presequence, p-F1 beta(1-18), was much less effective. ATIII, a helical peptide derived from antithrombin III, was not recognized by MPP. Synthetic peptides corresponding to 4, 6, and 11 amino acids of the C terminus of the presequence, p-F1 beta(51-54), p-F1 beta(49-54), and p F1 beta(44-54) were almost completely inert. Competition studies show that MPP recognizes the C-terminal domain of the presequence rather than the N-terminal domain. Furthermore, the alpha-helical element of the C-terminal domain is shown to be required for the recognition event. PMID- 7798200 TI - Biochemical and genetic characterization of PepF, an oligopeptidase from Lactococcus lactis. AB - Lactococcus lactis possesses a complex proteolytic system which is essential for its growth in milk. We characterized one of the peptidases of this system, oligopeptidase PepF, together with its structural gene. PepF hydrolyzed peptides containing between 7 and 17 amino acids with a rather wide specificity. It was purified to homogeneity. The N-terminal sequences of PepF and of peptides resulting from tryptic digestion of PepF were determined and used to design degenerate oligonucleotides which served to amplify a DNA fragment internal to pepF. This fragment was used as a probe to screen a lactococcal genomic library in Escherichia coli and to clone the entire gene pepF. The gene coded for a 70 kDa protein and was located on a 55-kilobase lactose-protease plasmid. A motif His-Glu-X-X-His, characteristic of metallopeptidases was evidenced. Two regions of PepF were found similar, first to a stretch of 43 amino acids around the zinc binding site of several other peptidases, second to a stretch of 33 amino acids well conserved among creatine and arginine kinases. Preliminary results suggest the presence of a second copy of pepF. PMID- 7798201 TI - Species difference in the G protein selectivity of the human and bovine A1 adenosine receptor. AB - The purified bovine brain A1-adenosine receptor has previously been shown to discriminate among closely related G protein alpha-subunits. To obtain analogous information for the human receptor, the cDNA coding for the human A1-adenosine receptor was inserted into a plasmid placing the synthesis of the receptor protein under the control of the MalE promoter. Following induction by maltose, active receptor accumulated in Escherichia coli membranes. Binding of the antagonist 8-[3H]cyclopentyl-1,3-dipropylxanthine to E. coli membranes (KD approximately 2 nM, Bmax approximately 0.2-0.4 pmol/mg) showed the appropriate pharmacological profile. Incubation of E. coli membranes with purified Go,i reconstituted guanine nucleotide-sensitive high affinity binding of the agonist ( )[125I] N6-3-(iodo-4-hydroxyphenylisopropyl)adenosine to the receptor (KD approximately 1 nM). In the presence of purified beta gamma-subunit, the recombinant receptor interacted equally well with the recombinant G protein alpha subunits Gi alpha-1, Gi alpha-2, Gi alpha-3; G(o) alpha displayed a lower affinity for the receptor while Gs alpha was inactive. Parallel experiments were carried out in bovine and human brain membranes pretreated with N-ethylmaleimide to inactivate the endogenous G(o)/Gi proteins; Gi alpha-3 was most potent in reconstituting 125I-HPIA binding to bovine membranes, while Gi alpha-1, Gi alpha 2, and G(o) alpha displayed similar affinities. However, in human membranes, Gi alpha-1, Gi alpha-2, and Gi alpha-3, were equipotent and high concentrations of G(o) alpha were required to promote 125I-HPIA binding. These observations show (i) that functional human A1-adenosine receptors were synthesized in E. coli; (ii) that the pattern of G protein coupling is identical for the recombinant human A1-receptor and its counterpart in the native membrane; (iii) and that species differences between bovine and human receptor exist not only in their pharmacological profile but also in their G protein specificity suggesting that species homologues of receptors may use different signaling mechanisms. PMID- 7798202 TI - Purification and properties of protoporphyrinogen oxidase from the yeast Saccharomyces cerevisiae. Mitochondrial location and evidence for a precursor form of the protein. AB - Protoporphyrinogen oxidase, the molecular target of diphenylether-type herbicides, was purified to homogeneity from yeast mitochondrial membranes and found to be a 55-kDa polypeptide with a pI of 8.5 and a specific activity of 40,000 nmol of protoporphyrin/h/mg of protein at 30 degrees C. The Michaelis constant (Km) for protoporphyrinogen IX was 0.1 microM. Due to the high affinity of the enzyme toward oxygen, the Km for oxygen could only be approximated to 0.5 1.5 microM. The purified enzyme contained a flavin as cofactor. Studies with rabbit antibodies to yeast protoporphyrinogen oxidase showed that the enzyme is synthesized as a high molecular weight precursor (58 kDa) that is rapidly converted in vivo to the mature (55 kDa) membrane-bound form. Protoporphyrinogen oxidase activity was found only in purified yeast mitochondrial inner membrane (not in the outer membrane). Acifluorfen-methyl, a potent diphenylether-type herbicide, competitively inhibited the purified enzyme (Ki = 10 nM). The mixed inhibition by acifluorfen-methyl previously reported for the membrane-bound protoporphyrinogen oxidase (Camadro, J.M., Matringe, M., Scalla, R., and Labbe, P. (1991) Biochem. J. 277, 17-21) was shown to be related to partial proteolysis of the enzyme. PMID- 7798203 TI - Molecular cloning of a mammalian hyaluronidase reveals identity with hemopexin, a serum heme-binding protein. AB - Hyaluronan is the most abundant glycosaminoglycan of the extracellular matrix and is a critical substrate for cellular attachment and locomotion. Little is known about the class of enzymes, termed hyaluronidases, that are responsible for hyaluronan catabolism in mammals. We have determined a partial amino acid sequence from a purified preparation of porcine liver hyaluronidase and have used this information as the basis for cloning complementary DNA that encodes the corresponding protein. When expressed in a recombinant baculovirus system, the protein exhibited hyaluronidase activity in a substrate-gel assay. The deduced sequence of this mammalian hyaluronidase is that of a 459-amino-acid polypeptide bearing four potential N-glycosylation sites as well as a copy of a proposed hyaluronan binding motif. Remarkably, amino acid sequence comparisons and immunologic cross-reactivities strongly suggest that the cloned protein is identical to hemopexin, an abundant, heme-binding serum protein. Although hemopexin has not previously been reported to possess any enzymatic activity, it includes a conserved domain found in collagenases, stromelysins, and other enzymes that metabolize the extracellular matrix. We conclude that hemopexin is the predominant hyaluronidase expressed in mammalian liver. PMID- 7798204 TI - Glucose deprivation and acute cycloheximide treatment stimulate system L amino acid transport in cultured vascular smooth muscle cells. AB - The effect of glucose deprivation on the uptake of leucine has been examined in cultured vascular smooth muscle cells isolated from rat aortae. Equimolar substitution of sucrose or fructose for glucose in the culture medium enhanced the uptake of leucine in a time- and concentration-dependent manner. The effect was first detectable after 12 h and reached the maximum, 2-fold, after 48 h with an apparent half-maximal effect at 1 mM glucose and could be reversed after 48 h of glucose refeeding. The enhanced leucine uptake was completely inhibited by 2 amino-2-norbornane-carboxylic acid, a specific substrate for System L, but not by alpha-(methylamino)isobutyric acid or lysine. Kinetic analyses indicated that this stimulation was mediated via a homogenous system with a 1.7-fold increase in the Vmax without any change in the Km (0.15 mM). Prolonged treatments with cycloheximide (10 micrograms/ml) or actinomycin D (10 micrograms/ml) blocked this glucose deprivation effect and its reversal. However, cycloheximide also very rapidly stimulated leucine uptake, reaching the maximum, 2.5-fold over the basal at 1 h. This effect occurred at concentrations that matched its inhibition on protein synthesis (half-maximal at 0.1 micrograms/ml) and could be reproduced with puromycin as well as actinomycin D. The stimulatory effect of cycloheximide was also accompanied by an increase in the Vmax but not in the Km, being sensitive to 2-amino-2-norbornane-carboxylic acid inhibition only, and appeared to occur in an additive manner to that of glucose deprivation. Although the uptake of leucine was stimulated by glucose deprivation and brief exposure to cycloheximide, these treatments had no effect on the efflux of the substrate. These results are all consistent with the System L amino acids transport activity in cultured rat vascular smooth muscle cells being under the control of at least two non-hormonal regulatory mechanisms, one that is likely to involve a labile repressor molecule and the other involving de novo protein synthesis as a result of chronic glucose deprivation. PMID- 7798205 TI - Smooth muscle caldesmon controls the strong binding interaction between actin tropomyosin and myosin. AB - We have demonstrated that caldesmon does not alter the affinity of weak binding actomyosin complexes when it inhibits actin-tropomyosin activation at physiological ratios (1 per 14 actins), and we proposed that it acts upon the strong binding complexes in the same way that troponin-tropomyosin does. We therefore compared the effect of caldesmon, caldesmon fragments, and troponin upon the interaction of the strongly bound complexes S-1.ADP, S-1.adenylyl imidodiphosphate (AMP.PNP), and N-ethylmaleimide-treated myosin subfragment-1 (NEM-S-1) with actin-tropomyosin. In 0.17 M ionic strength buffer [14C]iodoacetamide-labeled S1.ADP bound to actin-smooth muscle tropomyosin with no evidence of cooperativity; Kd = 0.8 +/- 0.3 microM (n = 5). Inhibitory concentrations of sheep aorta caldesmon or rabbit skeletal muscle troponin made the binding highly cooperative. At low levels of saturation the apparent Kd was 10-40 microM with 10 microM caldesmon and 8-20 microM with 6 microM troponin; at > 50% saturation the binding was indistinguishable from actin-tropomyosin alone. A similar result was obtained for the binding of [14C]iodoacetamide-labeled S 1.AMP.PNP to actin-smooth muscle tropomyosin at 0.03 M ionic strength (Kd = 0.47 +/- 0.05 microM). Binding was slightly cooperative and became highly cooperative in the presence of inhibitory concentrations of troponin, caldesmon, and the human caldesmon fragments H7 (amino acids 622-767) and H9 (amino acids 726-793). We conclude that caldesmon and troponin both act as allosteric effectors of the "on"/"off" equilibrium of actin-tropomyosin. 0.1 NEM-S-1/actin potentiated actin smooth muscle tropomyosin activation of myosin MgATPase 7-fold at 0.03 M ionic strength. Caldesmon inhibited the ATPase in the presence and absence of 0.5 microM NEM-S-1. NEM-S-1 reactivated actin-tropomyosin, which had been inhibited by troponin, caldesmon, H7, or H9. This is compatible with opposing effects of NEM-S-1 and caldesmon or troponin upon the actin-tropomyosin on/off equilibrium. PMID- 7798206 TI - Discrete structural domains determine differential endoplasmic reticulum to Golgi transit times for glucose transporter isoforms. AB - The rate of movement of the glucose transporter isoforms Glut1 and Glut4 from the endoplasmic reticulum (ER) to the Golgi apparatus was investigated by pulse labeling and monitoring endoglycosidase H resistance in mRNA-injected Xenopus oocytes and in 3T3-L1 adipocytes, a cell line that naturally expresses both transporter isoforms. Despite their high degree of sequence identity, Glut1 and Glut4 exhibited dramatically different transit times. The t1/2 values for ER to Golgi transit for Glut1 and Glut4 were < 1 and 24 h, respectively, in oocytes and approximately 5 and 20 min, respectively, in 3T3-L1 adipocytes. Pulse-chase in conjunction with sucrose density gradient analysis revealed that the rate limiting step in the ER to Golgi processing of Glut4 was exit from the ER and not retention in an early Golgi compartment. We analyzed the biosynthesis of Glut1/Glut4 chimeric transporters in Xenopus oocytes in order to determine whether specific domains in Glut1 and Glut4 were responsible for their distinct transit times. The first exofacial glycosylated loop and the cytoplasmic carboxyl terminal domain of Glut4 were crucial for its delayed exit from the ER. The first transmembrane, the first exofacial, and the cytoplasmic COOH-terminal domains of Glut1 were largely responsible for Glut1's rapid processing in the ER. Some of the chimeric transporters were not fully processed. Approximately 50% of chimeric molecules containing the cytoplasmic COOH-terminal domain of Glut1 and either the first transmembrane or first exofacial domain of Glut4 were retained in early Golgi compartments and prevented from complete maturation. Normal processing of these chimeras was achieved by replacing the cytoplasmic COOH-terminal domain of Glut1 with that of Glut4. These data suggest that amino acid residues within the glycosylated exofacial loop and the cytoplasmic COOH terminus participate in a rate-limiting step in the folding of both Glut1 and Glut4 or could act as transient ER retention signals. Additionally, these results show that even chimeric molecules constructed from two highly homologous proteins can exhibit aberrant folding and post-translational processing. PMID- 7798208 TI - Biochemical mechanism of HIV-1 Vpr function. Oligomerization mediated by the N terminal domain. AB - The human immunodeficiency virus, type 1 (HIV-1) genome encodes a 15-kDa accessory gene product, Vpr, that is essential for virus replication in primary monocytes/macrophages. Being present in the virion, Vpr is believed to function in the early phases of HIV-1 replication, including nuclear migration of the pre integration complex and/or transcription of the provirus genome. By gel filtration analysis of highly purified Vpr protein and its mutants, we demonstrate that HIV-1 Vpr exists as an oligomer. The N-terminal domain of Vpr (amino acids (aa) 1-42) is sufficient for oligomerization; however, deletion of aa 36-76 from Vpr disrupts oligomerization, suggesting that aa 36-42 are critical for Vpr oligomerization. As a result of Vpr oligomerization, basic aa residues within Vpr aa 1-73 are highly resistant to trypsin digestion, while those within Vpr aa 74-96 are easily accessible. Mutations within the leucine-/isoleucine-rich domain (aa 60-81), which was previously identified to be involved in Vpr interaction with a host cellular protein, rendered Arg62 more susceptible to trypsin digestion. Thus, the Vpr oligomeric structure must be extended into this domain. These results suggest a novel feature of HIV-1 Vpr that may be important for its functions. PMID- 7798209 TI - Characterization of a deaminated neuraminic acid-containing glycoprotein from the skin mucus of the loach, Misgurnus anguillicaudatus. AB - Using NMR spectroscopy and mass spectrometry, the major sialic acid of the skin mucus of the loach, Misgurnus anguillicaudatus was found to be 3-deoxy-D-glycero D-galacto-2-nonulosonic acid (KDN). We have subsequently devised a method to isolate a KDN-containing glycoprotein preparation from loach skin mucus. The method involves the sonication of the skin mucus with 0.05 M Tris-HCl, pH 8.0, to solubilize the glycoprotein, followed by DE52-cellulose chromatography of the extract, Nuclease P1 treatment, and Sepharose CL-4B gel filtration. The purified glycoprotein preparation was found to contain 38.5% KDN, 0.4% NeuAc, 24.6% GalNAc, 3.3% Gal, and 28.2% amino acids (w/w). The amino acid composition of this glycoprotein preparation revealed that it is unusually rich in Thr, and 6 amino acids, Thr, Ser, Glu (or Gln), Pro, Gly and Ala, account for 83% of the total amino acids. This glycoprotein is extremely poor in Cys, Met, Tyr, Phe, Arg, and Trp. Treatment of this glycoprotein with alkali resulted in the destruction of 83% of Thr suggesting that most of the sugar chains in this glycoprotein are linked through Thr. Alkaline borohydride treatment of 100 mg of the glycoprotein preparation, followed by Sephadex G-25 (superfine) gel filtration, yielded two major oligosaccharide alditols, I (15.4 mg) and II (15.6 mg). Using liquid secondary ion mass spectrometry and methylation analysis, I was identified to be KDN alpha 2-->6GalNAc-ol and II, KDN alpha 2-->6(KDN alpha 2-->3)-GalNAc-o1. KDN alpha 2-->6GalNAc is structurally similar to NeuAc alpha 2-->GalNAc found in ovine submaxillary glycoprotein while II represents a novel structure which contains two sialic acids linked to a GalNAc through both alpha 2-->3 and alpha 2 ->6 linkages. This structure has never been found in mucin type glycoproteins including mammalian epithelial mucin glycoproteins. This is the first report of the presence of a mucin type glycoprotein which contains KDN instead of NeuAc or NeuGc in fish skin mucus. PMID- 7798207 TI - Cloning, sequence analysis, and expression of the genes encoding the two subunits of the methylotrophic bacterium W3A1 electron transfer flavoprotein. AB - The genes encoding the two different subunits of the electron transfer flavoprotein (ETF) from the methylotrophic bacterium W3A1 have been identified, cloned, and sequenced. A 0.8-kilobase pair DNA fragment was generated for use as a molecular probe by the amplification of genomic sequences using the polymerase chain reaction and a primer pair with degenerate sequences derived from the NH2 terminal amino acid sequences determined for the ETF subunits purified from W3A1. The screening of a partial genomic minilibrary containing size-selected BamHI SalI fragments using this probe identified a 2.2-kilobase pair insert containing the complete coding sequences for both W3A1 ETF subunits. The genes are arranged in tandem in the genomic DNA with only 2 bases between the TAG translation termination codon of the small subunit and the ATG translation initiation codon of the large subunit. The deduced amino acid sequences of each of the W3A1 ETF subunits exhibit only approximately 30% identity with the corresponding subunits of the ETF from human, rat, and Paracoccus denitrificans, which as a group are greater than 50% identical. Thus, the ETF from W3A1 may exhibit some unique structural features that, like other differences in some of its physical and functional properties, may distinguish this ETF from others in this family. A highly homologous region near the COOH terminus of the large subunit in all the ETF proteins was found to contain a sequence that matches in several ways the ADP binding motif of flavoproteins and other dinucleotide-binding proteins, suggesting that the large subunit forms a portion of the FAD (or AMP) binding site in these proteins. Under control of the tac promoter, the cloned ETF subunit genes were co-expressed in Escherichia coli producing the heterodimeric holoprotein with physical, spectral, and electron-accepting properties essentially identical to the ETF isolated from W3A1. The recombinant ETF serves as the electron acceptor for W3A1 trimethylamine dehydrogenase in vitro, accumulating as the air-stable anionic semiquinone in the presence of excess trimethylamine. Fully reduced ETF could not be obtained even after prolonged enzymatic reduction. PMID- 7798211 TI - The stability of the molecular chaperonin cpn60 is affected by site-directed replacement of cysteine 518. AB - Cysteine 518 of the molecular chaperonin cpn60 (groEL) has been replaced with serine (C518S) by site-directed mutagenesis. The resulting mutant chaperonin protein is still functional and it can: (a) arrest the spontaneous folding of rhodanese in the absence of GroES and ATP, (b) assist refolding of the enzyme rhodanese in the presence of GroES and ATP/Mg2+, and (c) permit the urea-induced release and refolding of rhodanese from its complex with cpn60. ATP/Mg2+, alone, could discharge active rhodanese from cpn60 complexes formed with either wild type or C518S. In contrast with wild type cpn60, C518S has: (a) reduced stability of its quaternary structure, (b) reduced ability to reassemble tetradecamers after dissociation by urea; (c) reduced ATPase activity; and (d) more easily exposed hydrophobic surfaces. The data suggest that replacement of Cys-518 with Ser in cpn60 destabilizes its oligomeric structure, but there is no significant effect on cpn60 function or the stability of the monomers formed in urea. PMID- 7798210 TI - Analysis of an invariant cofactor-protein interaction in thiamin diphosphate dependent enzymes by site-directed mutagenesis. Glutamic acid 418 in transketolase is essential for catalysis. AB - A homologous expression system and a purification protocol for pure, highly active recombinant yeast transketolase have been developed. The invariant transketolase residue Glu418, which forms a hydrogen bond to the N-1' nitrogen atom of the pyrimidine ring of the cofactor thiamin diphosphate has been replaced by glutamine and alanine. Crystallographic analyses of the mutants show that these amino acid substitutions do not induce structural changes beyond the site of mutation. In both cases, the cofactor binds in a manner identical to the wild type enzyme. Significant differences in the CD spectra of the mutant transketolases compared with the spectrum of wild-type enzyme indicate differences in the electron distribution of the aminopyrimidine ring of the cofactor. The E418Q mutant shows 2% and the E418A mutant shows about 0.1% of the catalytic activity of wild-type enzyme. The affinities of the mutant enzymes for thiamin diphosphate are comparable with wild-type transketolase. The hydrogen bond between the coenzyme and the side chain of Glu418 is thus not required for coenzyme binding but essential for catalytic activity. The results demonstrate the functional importance of this interaction and support the molecular model for cofactor deprotonation, the first step in enzymatic thiamin catalysis. PMID- 7798213 TI - Structural and functional analysis of NF-kappa B. Determinants of DNA binding specificity and protein interaction. AB - The NF-kappa B transcription factors display a high degree of sequence conservation in a domain initially described in the rel oncogene. Two family members, NF-kappa B1 and NF-kappa B2, have distinct DNA binding properties and functionally distinct effects on different enhancers. NF-kappa B1, for example, binds to the kappa B site from the human immunodeficiency virus (HIV) with approximately 15-fold higher affinity than NF-kappa B2. In this study, we have defined regions within the Rel domain which determine DNA binding specificity and interaction with other proteins. We find that the COOH-terminal putative Rel dimerization domain of NF-kappa B1 is required for preferential binding to the HIV kappa B site. In contrast, preferential stimulation of the HIV enhancer by NF kappa B2 with RelA(p65) is determined by both the NH2- and COOH-terminal Rel domains of NF-kappa B2. These two regions of NF-kappa B2 also mediate preferential synergy with Bcl3. These data suggest that a specific subdomain of the Rel conserved region has evolved to control the fine specificity of DNA binding, and two distinct subregions within the Rel domain determine the specificity of interaction with other transcription factors. These specific Rel conserved domains therefore determine the specificity of NF-kappa B interactions and contribute to selective gene activation. PMID- 7798212 TI - Isolation and characterization of HL-60 cells resistant to nitroprusside-induced differentiation. AB - Sodium nitroprusside and sodium nitrite, which generate nitric oxide and increase the intracellular cGMP concentration, and 8-bromo-cGMP, a membrane-permeable cGMP analog, induce myelomonocytic differentiation of HL-60 cells (Boss, G. R. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7174-7178). We have selected HL-60 cells resistant to nitroprusside-induced differentiation as assessed by acquisition of the OKM-1 antigen, reduction of nitro blue tetrazolium, and morphologic maturation. The variant cells were also resistant to differentiation induced by sodium nitrite and two cGMP analogs but still differentiated in response to other inducing agents such as dimethyl sulfoxide and cAMP analogs and showed the same changes in c-myc and c-fos expression in response to the latter drugs as occurred in parental cells. We studied the early steps of the NO/cGMP signal transduction pathway in the variant cells and found that basal and nitroprusside-stimulated guanylate cyclase activity was similar in parental and variant cell extracts and that nitroprusside increased the intracellular cGMP concentration to the same extent in parental and variant cells. As part of these studies we found that HL 60 cells expressed only alpha 2 and beta 2 guanylate cyclase mRNA; the abundance of these two mRNA species was similar in parental and variant cells. Neither nitroprusside nor 8-bromo-cGMP changed the intracellular calcium concentration in parental or variant cells. The data suggest that the defect in the variant cells is after guanylate cyclase activation in the NO/cGMP transduction pathway and that the cGMP and cAMP transduction pathways operate independently in inducing differentiation of HL-60 cells. PMID- 7798215 TI - Investigation of the active site and the conformational stability of nucleoside diphosphate kinase by site-directed mutagenesis. AB - Nucleoside-diphosphate kinase (EC 2.7.4.6) catalyzes phosphate exchange between nucleoside triphosphates and nucleoside diphosphates. Its 17 kDa subunits are highly conserved throughout evolution in both sequence and tertiary structure. Using site-directed mutagenesis we investigated the function of 8 amino acids (Lys16, Tyr56, Arg92, Thr98, Arg109, Asn119, Ser124, and Glu133) that are totally conserved among all nucleoside diphosphate kinases known to date. The mutant proteins all show decreased specific activity and support roles for these residues in catalysis, substrate binding, or both, as was previously proposed on the basis of the x-ray structure (Morera, S., Lascu, I., Dumas, C., LeBras, G., Briozzo, P., Veron, M., and Janin, J. (1994) Biochemistry 33, 459-467). Furthermore, residues Lys16, Arg109, and Asn 119 were identified to play important roles in conformational stability or subunit interactions. We show that Lys16 and Asn119 form a rigid structure that is important for enzymatic function and that Arg109, known to interact with the phosphate moiety of the substrate, also plays an important role in subunit association. The dual roles of Lys16, Arg109, and Asn119 in both substrate binding and subunit assembly provide further evidence for a functional coupling between catalytic activity and quaternary structure in nucleoside diphosphate kinase. PMID- 7798216 TI - Functional and molecular characterization of the transcriptional regulatory region of the proacrosin gene. AB - Proacrosin, the zymogen form of the serine protease acrosin, is located within the acrosomal vesicle of mammalian spermatozoa and has been suggested to be involved in the fertilization process. In mouse and rat, expression of the proacrosin gene starts in pachytene spermatocytes and continues through the early stages of spermiogenesis. We have shown recently that 2.3 kilobase pairs of the 5'-flanking region of the rat proacrosin gene is sufficient to direct chloramphenicol acetyltransferase gene expression in a germ cell-specific and developmental stage-specific manner in the mouse. Additional transgenic lines have been generated which include two deletions in the 5'-flanking region and a tyrosinase minigene as marker for gene expression. Transgenic mice bearing these two truncated fragments showed different patterns of reporter gene expression. Transgenic lines (BM, B3, B2) harboring the 397-base pair (bp) fragment (from 45 to 442 bp upstream of ATG) showed no chloramphenicol acetyltransferase (CAT) activity in either testis or other tissues, but analysis via reverse transcription polymerase chain reaction confirmed low levels of reporter gene transcription in testis. Transgenic line TC bearing a longer fragment of 877 bp (from 45 to 922 bp upstream of ATG) showed a reporter gene expression and chloramphenicol acetyltransferase enzyme activity which was identical to that found in mice harboring the 2.3-kilobase pair 5'-flanking region. The analysis of the CAT gene expression during testicular development showed diploid transcription and haploid translation. It can be concluded that all sequences required for a basic level of testis-specific transcription of transgene are present within the 397-bp fragment, and other DNA sequences located outside of the 397-bp fragment but present within the 877-bp fragment can function as enhancer elements. Two fragments within the 877-bp region were identified by gel retardation assays as binding exclusively to nuclear factor(s) from testis protein extracts. In both fragments we identified sequence elements which are present in the promoter region of the germ cell-specific genes for histone H2B and protamine 1, respectively. PMID- 7798214 TI - Molecular characterization of native and recombinant apolipoprotein A-IMilano dimer. The introduction of an interchain disulfide bridge remarkably alters the physicochemical properties of apolipoprotein A-I. AB - The disulfide-linked dimer of apolipoprotein A-IMilano (A-IM/A-IM), a natural Arg173-->Cys variant of apoA-I, was purified from carriers' plasma and produced in Escherichia coli. The recombinant A-IM/A-IM is identical to native A-IM/A-IM, by mass spectrometry, SDS-polyacrylamide gel electrophoresis, and isoelectric focusing. Lipid-free A-IM/A-IM undergoes concentration-dependent self-association similar to apoA-I, but at all concentrations apoA-I is more self-associated than A-IM/A-IM. Far-ultraviolet CD spectra of A-IM/A-IM reveal a highly alpha-helical structure predicted to be approximately 65% in the lipid-free and approximately 78% in the lipid-associated states, versus 43 and 73% for apoA-I. A significant loss of alpha-helix occurs below pH 3.5 and above pH 10 in both apoA-I and A-IM/A IM; A-IM/A-IM constantly shows a higher alpha-helical content than apoA-I over the entire pH range (1.7-12.8), suggesting that hydrophobic forces stabilize the interaction between the two A-IM chains. Indeed, and differently from apoA-I, the alpha-helical content of A-IM/A-IM is minimally affected by solvent ionic strength. The aromatic side chains in both lipid-free and lipid-bound A-IM/A-IM are immobilized in a more asymmetric and hydrophobic environment than in lipid free apoA-I, the conformation of A-IM/A-IM being instead similar to that achieved by apoA-I following interaction with lipids. The present findings prove that rA IM/A-IM is structurally identical to the native protein; the conformation of A IM/A-IM is remarkably different from that of apoA-I, thus possibly explaining some of the peculiar functional properties of the apoA-IMilano dimer. PMID- 7798217 TI - A secondary phosphorylation of CREB341 at Ser129 is required for the cAMP mediated control of gene expression. A role for glycogen synthase kinase-3 in the control of gene expression. AB - The cAMP-dependent protein kinase (PKA) phosphorylates CREB327/341 at a single serine residue, Ser119/133, respectively. Phosphorylation at this site creates the sequence motif SXXXS(P), a consensus site of the glycogen synthase kinase-3 (GSK-3) enzyme (Fiol, C.J., Mahrenholz, A.M., Wang, Y., Roeske, R.W., and Roach, P.J. (1987) J. Biol. Chem. 262, 14042-14048). We examined the phosphorylation of CREB at the SXXXS(P) consensus site and its role in CREB transactivation to cAMP induction. Neither isoform of the GSK-3 enzyme (GSK-3 alpha or beta) utilizes CREB as its substrate unless CREB is already phosphorylated at Ser119/133. A 13 amino acid peptide containing the sequence surrounding Ser119/133 was phosphorylated by GSK-3, at Ser115/129, only after the primary phosphorylation of the peptide by PKA (at Ser119/133), suggesting that Ser115/129 is a GSK-3 phosphoacceptor site. Mutant CREB327/341 proteins containing Ser-->Ala substitutions confirmed Ser115/129 as the only GSK-3 phosphorylation site. Transfection assays of wild type and mutant Gal4-CREB fusion proteins in PC12 cells demonstrated that Ser-->Ala substitution of residue 129 of CREB341 impairs the transcriptional response to cAMP induction. Analogous mutation in CREB327 results in 70% decrease in its transactivation response to cAMP. In undifferentiated F9 cells, which are refractory to cAMP induction, transfected GSK-3 beta kinase induces a 60-fold increase in cyclic AMP response element dependent transcription, mediated via the endogenous CREB protein. We propose that the hierarchical phosphorylation at the PKA and GSK-3 sites of CREB are essential for cAMP control of CREB. PMID- 7798218 TI - Molecular characterization of phagosomes. AB - The transformation of newly formed phagosomes into mature phagolysosomes is a process that involves a complex series of interactions between phagosomes and other vacuolar organelles. The machinery required by phagosomes to mediate these interactions is poorly understood. In this study, we allowed human and various rodent cells to take up latex beads whose density facilitates a simple purification of phagosomes using discontinuous sucrose gradients. With this system, we initiated a systematic study of phagosome proteins using two dimensional gel electrophoresis and the currently available two-dimensional gel protein data bases. By this approach, we were able to recognize a group of polypeptides associated with mouse J774 phagosomes-phagolysosomes including annexin II, annexin VI, the beta-1 and beta-2 subunits of trimeric G proteins, and a group of actin-binding proteins. While the amount of annexin II associated to phagosomes was similar at all times of latex internalization, the levels of annexin VI were higher on late phagosomes. Phospholipid analysis of J774 phagosomes isolated at early and late time points during phagolysosome formation also revealed significant differences in their lipid composition. In the human phagosomes, we resolved over 200 polypeptides on the two-dimensional gels. These included the proteins described in the mouse, as well as 32 polypeptides that were found to be highly enriched in phagosomes, 15 of which are not present in the current data bases. The results demonstrate that the use of latex bead phagosomes is a powerful system to identify key molecules involved in phagolysosome biogenesis. PMID- 7798220 TI - Cleavage of the thyrotropin receptor does not occur at a classical subtilisin related proprotein convertase endoproteolytic site. AB - The human thyrotropin receptor (TSHR) undergoes proteolytic cleavage closely upstream to amino acid 317. Between residues 261 and 313 are three clusters of positively charged amino acids, arginines (Arg) and lysines (Lys), which are potential subtilisin-related proprotein convertase sites. We used oligonucleotide directed mutagenesis to perform conservative amino acid substitutions within these regions (Arg or Lys to glutamine, Gln). Chinese hamster ovary cells stably transfected with mutant receptor cDNA TSHR-CS1 (Gln261) and TSHR-CS3 (Gln312, Gln313) bound radiolabeled TSH with an affinity similar to the wild-type TSHR. Mutant cDNA TSHR-CS2 (Gln290, Gln291) and TSHR-CS4 (Gln261, Gln290, Gln291, Gln312, Gln313) did not express a protein on the cell surface capable of specific TSH binding. After covalent cross-linkage of radiolabeled TSH to TSHR-CS1 and TSHR-CS3, the mutant receptors dissociated into two subunits under reducing conditions. The most prominent cluster of basic amino acids in the TSHR extracellular region (residues 287-293) was studied in a second series of mutations designed to eliminate the classical proprotein convertase sites in this region and yet be compatible with TSHR function. All three mutant receptors, TSHR CS5 (Gln290), TSHR-CS6 (Gln291), and TSHR-CS7 (Gln291, Gln293) bound TSH with an affinity similar to that of wild type, and none of these amino acid substitutions prevented proteolytic cleavage of the extracellular domains of the TSHR. Thus, cleavage of the TSHR extracellular domain does not involve a classical subtilisin related proprotein convertase cleavage site, raising the possibility that TSHR cleavage occurs after processing and trafficking of the protein to the plasma membrane. PMID- 7798219 TI - The major kidney AE1 isoform does not bind ankyrin (Ank1) in vitro. An essential role for the 79 NH2-terminal amino acid residues of band 3. AB - The AE1 (band 3) protein mediates the exchange of anions across the erythrocyte plasma membrane and, via association with the adapter molecule, ankyrin (Ank1), forms the major link between the membrane and the underlying spectrin cytoskeleton. The major kidney isoform of AE1 (kAE1), a protein that is otherwise identical to erythroid AE1 but lacks the NH2-terminal 79 amino acids, is localized to the basolateral plasma membrane of acid-secreting (alpha-type) intercalated cells of distal nephron. It has been proposed that this polarized distribution of kAE1 is due, at least in part, to its association with the ankyrin-spectrin cytoskeleton. In this study, we have used cell-free binding assays to investigate the interaction of anion exchangers with an Ank1 fragment, R13-H, that contains the AE1 binding site. Microsomes from cells expressing full length erythroid AE1 bound 125I-labeled R13-H, revealing the presence of both high (Kd = 12.5 nM) and low (Kd = 166 nM) affinity sites. This binding was specific, as evidenced by the failure to observe high affinity binding of 125I R13-H to microsomes from cells transfected with vector alone or with AE1m, a mutant lacking the approximately 400 amino acid NH2-terminal cytoplasmic ankyrin binding domain. Using this assay, we could detect no high affinity association between kAE1 and 125I-R13-H. We conclude that the NH2-terminal 79 amino acids play an essential role in high affinity and specific binding of AE1 to Ank1. PMID- 7798221 TI - Heat-stable inhibitors of cAMP-dependent protein kinase carry a nuclear export signal. AB - The heat-stable inhibitor of cAMP-dependent protein kinase (PKI) was shown previously to export the kinase catalytic subunit (C) from the nucleus (Fantozzi, D. A., Harootunian, A. T., Wen, W., Taylor, S. S., Feramisco, J.R., Tsien, R. Y., and Meinkoth, J. L. (1994) J. Biol. Chem. 269, 2676-2686), in addition to its ability to inhibit kinase activity. In this study, the mechanism of PKI export is investigated. The injection of a C-PKI complex containing both labeled PKI and C subunit revealed that both proteins exit the nucleus in unison. A fusion protein of C-subunit with glutathione S-transferase (GST) (140 kDa) cannot transverse the nuclear membrane in either direction, but can be exported from the nucleus when complexed with PKI, supporting the presence of a nuclear export signal (NES) in the C-PKI complex. Fusions of PKI alpha with GST (70 kDa) or PKI beta 1 with maltose-binding protein (MBP) (50 kDa) remain effective at exporting complexes with C-subunit. The export of C-PKI is also sensitive to temperature and energy depletion. Taken together, these results demonstrate that export is both energy- and temperature-dependent, but size-independent, consistent with an active signal mediated export process. GST-PKI exits from the nucleus even in the absence of C subunit, indicating that the NES resides entirely on PKI, but suggesting that fusion of PKI to GST leads to a conformational change that mimics the exposure of the NES caused by the binding of C. Since both PKI alpha and PKI beta 1 can export C-subunit, the predicted export signal is likely to reside on the residues conserved between PKI alpha and PKI beta 1. PMID- 7798222 TI - Properties of recombinant mouse thrombospondin 2 expressed in Spodoptera cells. AB - A baculovirus system was used to express full-length recombinant mouse thrombospondin 2 (rTSP2) as a disulfide-bonded homotrimer with an NH2 terminus beginning with Asp20.rTSP2, like TSP1, was more sensitive to trypsin digestion if depleted of calcium ion. The trypsin digestion pattern of rTSP2 and TSP1 differed in that trypsin cut between the first and second type 1 modules of rTSP2. For bovine aortic endothelial cells adhering to TSP-coated polystyrene plates, reduction after coating caused both TSPs to be much more adhesive; these adhesions were blocked completely by RGDS peptide or antibody to alpha v beta 3 integrin.rTSP2 and TSP1 also mediated the adhesion of HT-29 human colon adenocarcinoma cells that carry alpha v beta 5 but not alpha v beta 3 integrin. Antibody to alpha v beta 5 did not inhibit adhesion of HT-29 cells to TSP1 or rTSP2. Rather, adhesion of HT-29 cells was decreased by treatment of TSPs with EDTA, abolished by reduction of the TSPs, and, in the case of rTSP2, blocked by heparin. Adhesion of MG63 cells to both TSPs was complex. Treatment with EDTA enhanced the adhesive activity of rTSP2 but decreased the adhesive activity of TSP1. These results show that TSP2 can be processed and secreted when overexpressed using baculovirus, TSP1 and rTSP2 differ in protease susceptibility in the type 1 module region, and TSP1 and rTSP2 mediate cell adhesion by complex and similar but not identical mechanisms. PMID- 7798223 TI - 1,25-dihydroxyvitamin D3 alters the effect of cAMP in thyroid cells by increasing the regulatory subunit type II beta of the cAMP-dependent protein kinase. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) attenuates the stimulatory effects of cAMP on proliferation and iodide uptake in rat thyroid FRTL-5 cells. This study examines the effects of 1,25-(OH)2D3 on the cAMP-dependent protein kinase (PKA). Cytosol proteins separated by anion exchange chromatography showed increased [3H]cAMP binding activity as well as increased kinase activity in the fractions containing PKA type II in 1,25-(OH)2D3 (10 nM)-treated cells compared to the control cells. Western blot analysis of 1,25-(OH)2D3-treated cells revealed a 4 fold increase in the cytosolic amount of the PKA regulatory subunit RII beta, whereas no changes were detected in the regulatory subunits RI alpha and RII alpha or the catalytic (C) subunit. Northern blot analyses showed a similar increase in RII beta mRNA in cells treated for 12 h with 1,25-(OH)2D3 (10 nM), and RII beta mRNA increased further to 10-fold above control cell level after 96 h of incubation. Iodide uptake was synergistically stimulated with both PKAI- and PKAII-directed pairs of cAMP analogs. The PKAI synergism was, however, inhibited by 1,25-(OH)2D3 treatment of the cells, whereas the PKAII synergism was unaffected. In conclusion, 1,25-(OH)2D3 attenuates both PKAI formation and PKAI stimulated iodide uptake in rat thyroid FRTL-5 cells by increasing the level of RII beta without altering the other PKA subunit levels. PMID- 7798224 TI - Expression and characterization of human and chimeric human-Paracoccus denitrificans electron transfer flavoproteins. AB - Electron transfer flavoprotein (ETF) is a heterodimer that contains a single equivalent of FAD and accepts electrons from nine flavoprotein dehydrogenases in the mitochondrial matrix. Human ETF was expressed in Escherichia coli using the expression vector previously employed to express Paracoccus denitrificans ETF (Bedzyk, L. A., Escudero, K. W., Gill, R. E., Griffin, K. J., and Frerman, F. E. (1993) J. Biol. Chem. 268, 20211-20217). cDNAs encoding the beta and alpha subunits of the human protein were inserted into the vector, mimicking the arrangement of the P. denitrificans genes in which coding sequences are joined by overlapping termination and initiation codons. A human ETF containing 30% P. denitrificans sequence at the amino terminus of the beta subunit was also expressed and purified. This chimeric ETF has 64% sequence identity with the human sequence in the substituted region. Kinetic constants of medium chain and short chain acyl-CoA dehydrogenases for the chimeric ETFs were slightly changed from those of human ETF; but, there are marked differences in the kinetic constants of sarcosine dehydrogenase and electron transfer flavoprotein ubiquinone oxidoreductase with the two ETFs. Absorption spectra of the three redox states of human, chimeric, and P. denitrificans ETF flavins are identical. However, the flavin circular dichroism spectra of the three ETFs are characteristic for each species. The spectrum of the chimeric ETF has both human and P. denitrificans ETF features. The amplitude of the 436 nm band is identical to that of the of the human ETF flavin, but the amplitude of the 375 nm band is identical to that of the P. denitrificans ETF flavin. Thus, flavin in the chimeric ETF appears to be exposed to dipoles in the protein framework provided by human and bacterial sequences. These spectral data indicate that the flavin is located in the vicinity of the amino-terminal region of the beta subunit. The kinetic data suggest that the amino-terminal region of the beta subunit comprises part of the docking site for some primary dehydrogenases and electron transfer flavoprotein-ubiquinone oxidoreductase. PMID- 7798225 TI - The regulation of capacitative calcium entry by calcium and protein kinase C in Xenopus oocytes. AB - Agonists linked to the phosphoinositide signaling pathway evoke capacitative calcium entry in Xenopus oocytes. This entry pathway can also be activated by injection of inositol 2,4,5-trisphosphate, application of thapsigargin, or incubation in calcium-free medium. A variety of protocols revealed highly nonlinear behavior of the calcium entry in thapsigargin-treated oocytes suggestive of positive and negative feedback by calcium at the level of its own entry. These feedback mechanisms may account for the highly damped calcium oscillations we observed in thapsigargin-treated oocytes. Low level activation of protein kinase C potentiated calcium influx in thapsigargin-treated oocytes, apparently by blocking the inactivation of the calcium influx. Higher levels of protein kinase C activity inhibited capacitative calcium entry. PMID- 7798226 TI - Identification of chloroplast envelope proteins in close physical proximity to a partially translocated chimeric precursor protein. AB - Translocation intermediates of the chimeric protein precursor Oee1-Dhfr were generated and used to identify envelope components in close proximity to the arrested precursor. The translocation of Oee1-Dhfr across the chloroplast envelope can be arrested at low ATP levels or by prebinding the fusion precursor with anti-Dhfr IgGs. The arrested Oee1-Dhfr precursor appears to span both the outer and inner envelope membranes. Translocational arrest of Oee1-Dhfr by low ATP levels was reversible, and import was restored upon resupplementation with higher ATP levels. Chemical cross-linking and co-immunoprecipitation with monospecific antibodies indicate that two outer envelope membrane proteins (Com44 and Com70) and at least one inner envelope protein (Cim44 and Cim97) were found to be in close proximity to Oee1-Dhfr during translocation. The Com70 protein was further studied and additional evidence for its role in chloroplast protein import is presented. PMID- 7798227 TI - Effects of neurohormonal stress and aging on the activation of mammalian heat shock factor 1. AB - The mammalian heat shock response has been investigated extensively using tissue culture cells with only a limited amount of information available on animals and intact tissues. The neurohormonal stress response mediated by the hypothalamic pituitary-adrenal axis leads to the activation of heat shock factor (HSF) in rat adrenal tissue. Here we show through the use of antibodies specific to each member of the HSF family that restraint-induced stress in intact Wistar rats and adrenocorticotropic hormone treatment of hypophysectomized animals leads to the activation of HSF1 monomers to trimers with DNA-binding activity. Because HSF1 is also the target factor for metabolic and environmental stress, these data reveal an intersection of pathways leading to HSF1 activation. Comparison of the biochemical properties and levels of HSF1 in the Wistar and Fischer 344 rat strains reveals that HSF1 is constitutively present in an activated DNA-binding state in the adrenals of Fischer 344 rats. During aging, the levels of HSF1 remain constant, yet the transcription factor from aged animals exhibits a decreased ability to bind DNA. PMID- 7798228 TI - Purified yeast translational initiation factor eIF-3 is an RNA-binding protein complex that contains the PRT1 protein. AB - Eukaryotic initiation factor-3 (eIF-3) plays a pivotal role in the initiation phase of protein synthesis where it promotes dissociation of 80 S ribosomes into subunits, stabilizes methionyl-tRNAi binding to 40 S ribosomal subunits, and is required for mRNA binding. Mammalian eIF-3 is comprised of eight subunits, but no mammalian cDNA encoding these proteins has been cloned and sequenced, nor has the corresponding factor been characterized in yeast. Since many initiation factors are strongly conserved between mammalian and yeast systems, we employed a mammalian assay for initiation, the synthesis of methionyl-puromycin, to detect eIF-3 activity in yeast subcellular fractions. Yeast eIF-3 was purified from the high salt wash of ribosomes by Superose 6 molecular sieve and MonoS ion exchange chromatography. Yeast eIF-3 contains eight subunits with masses of 16, 21, 29, 33, 39, 62, 90, and 135 kilodaltons all of which coelute with an apparent mass of 550 kilodaltons from the Superose 6 column. Immunoblotting shows that the 90-kDa subunit corresponds to the product of the PRT1 gene whose mutant form, prt1-1, exhibits destabilization of methionyl-tRNAi binding to 40 S ribosomal subunits. eIF-3, and specifically the 62-kDa subunit, bind to RNA. These biochemical approaches to defining yeast eIF-3 complement genetic methods so far used in characterizing the initiation factors and provide another route to defining the yeast translational machinery. PMID- 7798229 TI - Receptor-mediated endocytic uptake of methylglyoxal-modified serum albumin. Competition with advanced glycation end product-modified serum albumin at the advanced glycation end product receptor. AB - Methylglyoxal binds and irreversibly modifies arginine and lysine residues in bovine serum albumin (BSA) under physiological conditions, producing a protein with an increased net negative charge at physiological pH. At 4 degrees C, methylglyoxal-modified BSA (MG-BSA) was bound by cell surface receptors on murine P388D1 macrophages. The apparent dissociation constant KD value was 435 +/- 2 nM, and there were 8.89 +/- 0.02 x 10(5) receptors/cell (n = 6), compare with an apparent KD value of 263 +/- 52 nM and 10.17 +/- 0.93 x 10(5) receptors/cell (n = 11) for advanced glycation end product-modified BSA (AGE-BSA). AGE-BSA competed with MG-BSA for binding to a common receptor; however, a component of AGE-BSA receptor binding could not be displaced by MG-BSA, and a component of MG-BSA receptor binding could not be displaced by AGE-BSA, suggesting that there are binding sites for both AGE-BSA and MG-BSA, competitive and noncompetitive, to MG BSA and AGE-BSA on P388D1 cells at 4 degrees C. At 37 degrees C, receptor binding of AGE-BSA and MG-BSA was followed by endocytosis and lysosomal degradation of the modified protein. Methylglyoxal-modified proteins are ligands for the AGE receptor, and their formation and metabolism may be linked to the development of diabetic complications. PMID- 7798230 TI - Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. AB - The physiological alpha-oxoaldehyde methylglyoxal binds and modifies arginine, lysine, and cysteine residues in proteins. The kinetics and mechanism of these reactions were investigated with N alpha-acetylamino acids and bovine serum albumin at pH 7.4 and 37 degrees C. The reaction of methylglyoxal with N alpha acetylarginine involved the initial reversible formation of glycosylamine and 4,5 dihydroxy-5-methylimidazolidine derivatives, with further slow irreversible conversion to an imidazolone, N alpha-acetyl-N delta- (5-methyl-4-imidazolon-2 yl)ornithine. The imidazolone was fluorescent with an excitation lambda max value of 320 nm and an emission lambda max value of 398 nm. Methylglyoxal reacted reversibly with N alpha-acetyllysine to form glycosylamine and bisglycosylamine derivatives. Further reaction of these glycosylamines occurred to form brown, fluorescent oligomers that were not characterized. Methylglyoxal reacted rapidly and reversibly with N alpha-acetylcysteine to form the hemithioacetal adduct. The reaction of methylglyoxal with bovine serum albumin (BSA) at pH 7.4 and 37 degrees C involved the reversible and irreversible formation of methylglyoxal-BSA adducts. Irreversible modification of BSA occurred mainly on arginine residues to form imidazolone. The formation of methylglyoxal-modified proteins involves glycoxidation leading to advanced glycation end product-like fluorescence. It is expected to be increased in diabetes mellitus and may be linked to the development of diabetic complications. PMID- 7798231 TI - Transition state structures for the hydrolysis of alpha-D-glucopyranosyl fluoride by retaining and inverting reactions of glycosylases. AB - Secondary tritium and primary 14C kinetic isotope effects were measured for the hydrolysis of alpha-D-glucopyranosyl fluoride catalyzed by sugar beet seed alpha D-glucosidase, forming alpha-D-glucose, and by Rhizopus niveus glucoamylase forming beta-D-glucose. The data provided a novel opportunity to model and directly compare the transition state structures for the hydrolysis of a substrate promoted with retention or inversion of configuration according to the enzyme catalyst. The isotope effects for the reaction catalyzed by each enzyme are most consistent with an SN1 rather than an SN2 mechanism. The modeled transition state structures for the hydrolysis promoted by the alpha-glucosidase and the glucoamylase both bear significant oxocarbonium ion character, with the D glucosyl residue having a flattened 4C1 conformation and a C-1-O-5 bond order of 1.92, even though opposite D-glucose anomers were produced from the substrate. The transition states show some modest differences, but their general similarity strongly suggests that the stereochemical outcome of glycosylase reactions does not predict the transition state structure, nor does the transition state structure of such reactions predict the stereochemical outcome. The results support previously reported evidence for the separate topological control of product configuration by protein structures in these and other glycosylases. PMID- 7798232 TI - Second-site suppressor mutations at glycine 218 and histidine 245 in the alpha subunit of F1F0 ATP synthase in Escherichia coli. AB - The alpha-like subunits of F1F0 ATP synthases share primary structural homology in two segments near their carboxyl termini. However, the amino acids at the functionally important positions occupied by alpha Gly-218 and alpha His-245 in Escherichia coli vary depending upon organism and organelle. The alpha G218- >D,H245-G and alpha G218-->K,H245-->G double mutations were constructed in the E. coli uncB(alpha) gene to model the chloroplast ATPase IV subunit and alkaliphilic bacterial alpha subunit, respectively. Strains carrying each of the single mutations, alpha G218-->D, alpha G218-->K, and alpha H245-->G, had marked reductions in F1F0 ATP synthase function. The alpha G218-->K mutation was alone sufficient to virtually eliminate enzyme function. Membranes prepared from the alpha G218-->D mutant exhibited increased levels of ATP hydrolysis activity without a corresponding increase in active proton transport, suggesting a mechanistic uncoupling of catalytic activity and proton translocation. However, much of the lost F1F0 ATP synthase activity was restored in the alpha G218- >D,H245-->G and alpha G218-->K,H245-->G double mutant strains demonstrating that these mutations act as mutual intragenic second-site suppressors. The evidence is consistent with a close spatial interaction between alpha Gly-218 and alpha His 245. PMID- 7798233 TI - The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. AB - Stimulation of antigen receptors of lymphocytes triggers a transitory release of Ca2+ from internal stores and the opening of a transmembrane Ca2+ conductive pathway. The latter underlies the sustained increase of intracellular free calcium concentration, and it seems to be a key event in the Ca(2+)-dependent biochemical cascade leading to T cell proliferation. Alternatively, pharmacological depletion of internal stores by itself activates Ca2+ influx. This has led to the hypothesis that antigen-triggered Ca2+ influx is secondary to Ca2+ release from internal stores. However, the precise relationship between antigen and Ca2+ release-activated Ca2+ currents remains unclear, particularly since neither of them has been electrophysiologically recorded in normal lymphocytes. Using the whole-cell and the perforated configurations of the patch clamp technique on peripheral blood lymphocytes, we found that a low amplitude Ca(2+)-selective current was triggered when intracellular stores were depleted by stimuli such as the intracellular perfusion of inositol triphosphate or thapsigargin and the extracellular perfusion of ionomycin. A similar current was elicited by the cross-linking of the T cell receptor-CD3 complex. This current displayed an inward rectification below 0 mV and was completely blocked by the divalent cation Cd2+. It was very selective for Ca2+ over Na+ and insensitive to changes in chloride concentration. The physiological relevance of this conductance was investigated with the analysis of abnormal Ca2+ signaling in lymphocytes from a patient suffering from a primary immunodeficiency associated with a defective T cell proliferation. Using fura-2 video imaging, an absence of Ca2+ influx was established in the patient's lymphocytes, whereas the Ca2+ release from internal stores was normal. This was the case whether cells were stimulated physiologically through their antigen receptors or with store depleting pharmacological agents. Most importantly, no Ca(2+)-selective current was elicited in these cells. Our data strongly suggest that the Ca2+ release activated current underlies the sustained Ca2+ influx during antigenic stimulation and that it plays a key role in the immune function. PMID- 7798235 TI - Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. AB - The effect of phosphoinositides on the activity of protein kinase C (PKC) isotypes was investigated. PKC alpha, beta I, beta II, gamma, delta, epsilon, eta, and zeta were expressed in baculovirus-infected insect cells and purified by column chromatography. The calcium-activated PKC isotypes alpha, beta I, beta II, and gamma were not significantly activated by any of the phosphoinositides investigated (phosphatidylinositol-4-phosphate (PtdIns-4-P), PtdIns-3-P, PtdIns 4,5-P2, PtdIns-3,4-P2, and PtdIns-3,4,5-P3) when added in the presence of concentrations of phosphatidylserine that give maximal stimulation. The calcium insensitive PKC isotypes delta, epsilon, and theta also showed little response to PtdIns-3-P, PtdIns-4-P, or PtdIns-4,5-P2 when these lipids were added in the presence of phosphatidylserine. In contrast, PtdIns-3,4-P2 and PtdIns-3,4,5-P3 caused a 5-15-fold stimulation of these enzymes compared with phosphatidylserine alone. 50% maximal stimulation of PKC epsilon by PtdIns-3,4,5-P3 occurred when this lipid was present at about 1% of the carrier PtdIns-4,5-P2 (about 100 nM). These lipids had little effect on baculovirus-expressed PKC zeta, which was constitutively active. A short chain version of PtdIns-3,4,5-P3, dioctanoyl PtdIns-3,4,5-P3, activated PKC delta, epsilon, and eta in the absence of other lipids, whereas a short chain version of PtdIns-4,5-P2, dihexanoyl-PtdIns-4,5-P2, did not. Since PtdIns-3,4-P2 and PtdIns-3,4,5-P3 are nominally absent in unstimulated cells and appear within seconds to minutes of stimulation by various cell activators, these lipids could act as second messengers to activate PKC delta, epsilon, or eta in vivo. PMID- 7798236 TI - Co-expression of cholesteryl ester transfer protein and defective apolipoprotein E in transgenic mice alters plasma cholesterol distribution. Implications for the pathogenesis of type III hyperlipoproteinemia. AB - Despite the definite etiologic link between apolipoprotein (apo) E mutations and type III hyperlipoproteinemia (HLP), it is not clear what additional factors are involved in the development of florid hyperlipidemia and how to explain the wide variability in the expression of the hyperlipidemic phenotype in carriers of receptor binding-defective apoE variants. The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP. We produced double transgenic mice that co-expressed high levels of simian CETP and either high or low levels of a human receptor binding-defective apoE variant, apoE(Cys-142). We previously reported that apoE(Cys-142) high-expresser mice showed spontaneous hyperlipidemia and accumulation of beta-VLDL, whereas the low-expresser mice showed only a modest increase in VLDL cholesterol. Co-expression of CETP induced a massive transfer of cholesteryl esters from the HDL to the VLDL in both lines of double-transgenic mice. As a result, HDL cholesterol and apoA-I levels were reduced to about 50% of normal, VLDL cholesterol increased 2.5-fold, and the cholesteryl ester content of VLDL reached values similar to those observed in human beta-VLDL. The ratio of defective to normal apoE in VLDL was unaffected by CETP co-expression and was higher in animals expressing high apoE levels. Finally, in spite of an increased accumulation of beta-VLDL in the high-expresser mice, the VLDL of the low-expresser mice maintained pre-beta mobility upon co expression of CETP. The results of this study demonstrate that the ratio of defective to normal apoE on the VLDL, rather than the cholesteryl ester content of VLDL, is the major factor determining the development of severe hyperlipidemia and the formation and accumulation of beta-VLDL in type III HLP. PMID- 7798234 TI - Stimulation of yeast adenylyl cyclase activity by lysophospholipids and fatty acids. Implications for the regulation of Ras/effector function by lipids. AB - A reconstituted system containing membranes prepared from various Saccharomyces cerevisiae strains (CYR1 ras1 ras2) and a recombinant RAS2 protein was used to evaluate the effect of lipids on adenylyl cyclase activity. Incubation of wild type membranes with lysophosphatidylinositol, lysophosphatidylserine, or lysophosphatidylcholine stimulated adenylyl cyclase activity in the absence and presence of RAS between 2-10-fold depending upon the individual lipid. Unsaturated fatty acids preferentially increased activity 2-3-fold in the presence of RAS. Other phospholipids as well as several detergents had only marginal effects on adenylyl cyclase activity. Lipids had no effect on either the binding or hydrolysis of GTP by RAS. LysoPI decreased both the Km for ATP and the amount of RAS required for enzyme activation. Four catalytically active deletion mutants of the CYR1 protein including one containing only the C-terminal 417 amino acids were similarly responsive to lysoPI when compared to the wild-type enzyme. These data suggest that lysophospholipids and fatty acids, metabolites of the mitogenically responsive enzyme phospholipase A2, may represent a novel mechanism for modulating the activity of downstream effector molecules and their interaction with Ras proteins. PMID- 7798237 TI - Rational reconstruction of the active site of a class mu glutathione S transferase. AB - Isoenzymes 3-3 and 4-4 of the mu class glutathione S-transferases share 77% sequence identity but have distinctly different catalytic properties. Analysis of the crystal structure of isoenzyme 3-3 in complex with the diastereomeric products of the addition of GSH to phenanthrene 9,10-oxide (Ji, X., Johnson, W. W., Sesay, M. A., Dickert, L., Prasad, S. M., Ammon, H. L., Armstrong, R. N., and Gilliland, G. L. (1994) Biochemistry 33, 1043-1052) reveals that 3 residues that are in van der Waals contact with the xenobiotic portion of the product are different in the type 4 subunit. The three mutations, V9I, I111A, and S209A, have been introduced into isoenzyme 3-3 individually and in combination in an attempt to minimally reconstruct the active site of the enzyme to mimic the type 4 subunit in structure and function. The results suggest that the V9I mutation is an important determinant in the stereoselectivity of the enzyme toward enones and epoxides. The I111A mutation increases the catalytic efficiency of the enzyme toward para-substituted 4-phenyl-3-buten-2-ones (XPBO) as measured by kcat/KmXPBO but does not affect kcat. The S209A mutation has no effect on catalysis. The double and triple mutants V9I/I111A and V9I/I111A/S209A exhibit both a high stereoselectivity and high kcat/KmXPBO comparable to that of isoenzyme 4-4. Analysis of substituent effects on the kinetics and stereoselectivity of the enzyme toward the enone substrates suggests that the mechanistic bases for the catalytic behavior of the isoenzyme 4-4 and the reconstructed mutants are not identical. The results provide functional evidence for the catalytic importance of specific residues previously identified by x-ray crystallography. PMID- 7798238 TI - Molecular cloning of a proteolytic antibody light chain. AB - The cDNA for an antibody light chain raised by immunization against vasoactive intestinal peptide (VIP) was cloned in a bacterial expression vector, and the recombinant light chain was purified to electrophoretic homogeneity. The light chain catalyzed the hydrolysis of VIP efficiently owing to its comparatively high affinity for the substrate. In control experiments, the catalytic activity was preserved at a constant level after further chromatography of the light chain on anion-exchange and gel-filtration fast protein liquid chromatography columns, and it was removed by immunoadsorption with immobilized anti-mouse light chain antibody. The amide bond linking methylcoumarinamide (MCA) and arginine in a tripeptide unrelated in sequence to VIP was cleaved by the light chain with lower affinity and kinetic efficiency (kcat/Km). Hydrolysis of the peptidyl-MCA conjugate was inhibited competitively by the alternate substrate, VIP. The Ki and Km values for VIP were in the same range, indicating that peptide-MCA and VIP hydrolysis occurs at a common catalytic site in the light chain. Molecular modeling suggested the presence of a serine protease-like site in the light chain. This was supported by inhibition of the hydrolytic activity by serine protease inhibitors, but not by inhibitors of other classes of proteases. These observations suggest a poorly discriminatory catalytic site, with specificity for VIP arising chiefly by means of the antigen recognition function of the light chain combining site. PMID- 7798240 TI - Amino acid residues of the kringle-4 and kringle-5 domains of human plasminogen that stabilize their interactions with omega-amino acid ligands. AB - Regions of the human plasminogen (Pg) cDNA containing its kringle 4 (K4) and K5 domains have been expressed in Escherichia coli, and binding constants of omega amino acid ligands for recombinant (r)-[K4Pg] and r-[K5Pg] have been obtained. In each case, the results showed that of a series of aliphatic alpha, omega-amino acid analogues, 6-aminohexanoic acid showed maximal affinity for these modules, and all ligands interacted more strongly with r-[K4Pg] than with r-[K5Pg]. Site directed mutagenesis investigations demonstrated that the major amino acid side chain contributors to ligand binding were similar for each of these kringles. Ligand binding was stabilized by charged groups at Asp56 of r-[K4Pg] and Asp57 of r-[K5Pg] as well as by Arg69 of both r-[K4Pg] and r-[K5Pg]. Some hydrophobic amino acids that contributed significantly to the binding strength of the ligands were identified. These were provided by homologous residues in each of the domains, viz. Trp60 and Trp70 of r-[K4Pg] and Trp62 and Tyr72 of r-[K5Pg]. Tyr74 of r-[K5Pg] also substantially contributed to its ligand binding energy. PMID- 7798239 TI - The Caenorhabditis elegans small GTP-binding protein RhoA is enriched in the nerve ring and sensory neurons during larval development. AB - p21 Ras has been implicated in vulval differentiation in Caenorhabditis elegans. We now describe the characteristics during nematode development of the related p21 RhoA which has been ascribed a morphological role in mammals. The CeRhoA cDNA isolated in this study encodes a sequence of 192 amino acids residues with 87.6% identity to human RhoA. Genomic Southern analysis indicates the presence of a single Rho gene in C. elegans. Its 2-kilobase mRNA is expressed at the highest levels during embryogenesis and decreases gradually thereafter. However, the level of the 24-kDa protein detected by the anti-CeRhoA antibody is high at the larval stages but low in embryos. The glutathione S-transferase/CeRhoA fusion protein expressed in Escherichia coli displays conserved biochemical activities. Unlike its counterpart in mammalian cells which is predominantly cytosolic, most of CeRhoA is associated with the membrane and the cytoskeleton throughout development. Indirect immunofluorescence analysis indicates an ubiquitous expression of CeRhoA throughout development with a particular enrichment at larval stages in the pharyngeal nerve ring and at the tip of the head containing chemosensory and mechanosensory neurons. This suggests a stage-specific role for p21 RhoA in mediating the signaling pathway underlying the sensory circuitry in C. elegans post-embryonic development. PMID- 7798241 TI - Dynamin 1 antisense oligonucleotide treatment prevents neurite formation in cultured hippocampal neurons. AB - Dynamin 1 (D100) is a microtubule-activated GTPase that is believed to play a role in the early steps of receptor-mediated endocytosis. Previous studies on the characterization of the Drosophila dynamin gene homolog, known as shibire, suggest that this protein may also participate in the formation of neuronal processes. To understand the role of rat brain dynamin 1 in neuronal morphogenesis, we correlated the intracellular levels of dynamin with the formation of neurites in rat hippocampal neurons and neuroblastoma N1E-115 cells in vitro. Quantitative Western and Northern blot analyses show that dynamin levels increase during neurite formation in both the hippocampal neurons and N1E 115 cells and decrease in N1E-115 cells during serum-induced neurite retraction. Furthermore, using antisense technology, we investigated the effect of decreased intracellular levels of dynamin on neurite formation in cultured embryonic hippocampal neurons. Antisense oligonucleotides against sequences surrounding the initiation codon of the rat brain dynamin gene (D100) reduce the intracellular levels of dynamin by approximately 90% and impair the formation of the minor and axon-like processes in a dose-dependent manner. Taken together, these results suggest that dynamin-mediated processes are necessary for normal neuronal morphogenesis. PMID- 7798242 TI - Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk. AB - The Fc receptor for IgG in platelets was identified as the integral membrane isoform encoded by the Fc gamma RIIA gene. Functional analysis of this molecule determined that activated Fc gamma RIIA is tyrosine phosphorylated and that activation induced the physical association with the protein tyrosine kinase p72syk. Other tyrosine-phosphorylated molecules also co-immunoadsorbed with the activated receptor. Tyrosine kinase activity co-immunoadsorbing with the platelet Fc gamma R was enhanced upon activation and specifically induced the phosphorylation, on tyrosine residues, of a physically associated 72-kDa protein. These data support a model of Fc gamma receptor-mediated platelet activation where signal is transduced through inducible association of the tyrosine kinase p72syk with the low affinity Fc gamma receptor. Thrombin, a potent platelet agonist, has been shown to up-regulate the activity of the tyrosine kinase p72syk in platelets. Consequently, our findings identify a second pathway by which p72syk is activated in platelets. PMID- 7798243 TI - Activation of prothrombin by a novel membrane-associated protease. An alternative pathway for thrombin generation independent of the coagulation cascade. AB - We herein report that a novel membrane-associated protease capable of activating prothrombin is present in several mammalian cells. This protease can directly convert prothrombin to active thrombin and induces blood clotting both in vivo and in vitro but is apparently different from coagulation factor Xa, which has been thought to be the only physiological activator of prothrombin. This protease activity was initially found and was very high in 8C feline kidney fibroblast cells, and we characterized its enzymological features using this cell line. Activity was detected in neither the cytosolic fraction nor the culture medium but found in the membranes and identified on the surface of intact cells. The activation of prothrombin required Ca2+ ions, and the apparent Km value for prothrombin was 0.2 microM. The activity was irreversibly inhibited by exposure to EDTA, but various inhibitors for serine proteases including antithrombin III were without effect. Based on these results, we propose that this novel enzyme, membrane-associated prothrombin activator, catalyzes an alternative pathway for generation of thrombin, which is independent of the blood coagulation cascade, and that the thrombin generated is involved in certain pathological states and/or in activation of cells that are spatially separated from the bloodstream. PMID- 7798244 TI - Protein kinase C zeta is associated with the mitotic apparatus in primary cell cultures of the shark rectal gland. AB - Protein kinase C zeta (PKC zeta) is an atypical PKC isoform that has recently been implicated in cell division and cell growth. However, there has been no morphologic evidence for the involvement of PKC zeta in mitogenic signal transduction. Here we use immunocytochemistry to demonstrate that PKC zeta co localizes with microtubules in both interphase and metaphase cells of the shark rectal gland in primary culture. This co-localization is present after non-ionic detergent treatment and is disrupted by nocodazole. During mitosis, PKC zeta is associated with the mitotic apparatus and co-localizes with beta-tubulin in spindle microtubules, while entirely sparing astral microtubules. These findings provide the first evidence that PKC zeta is associated with the mitotic apparatus. The striking presence of PKC zeta in the central portion of the mitotic apparatus suggests a functional role for this kinase isoform in cell division. PMID- 7798245 TI - Structural organization of the human oxytocin receptor gene. AB - We isolated and characterized the human oxytocin receptor gene. Southern blots indicated that the human genome has a single copy of the gene. Chromosomal localization by fluorescence in situ hybridization also showed that the gene was a single copy, assigned to 3p26.2 of the human chromosome. The gene spans approximately 17 kilobases and contains 3 introns and 4 exons. Exons 1 and 2 correspond to the 5'-non-coding region, followed by exons 3 and 4 encoding the amino acids of the receptor. Intron 3, which is the largest at 12 kilobases, separates the coding region immediately after the putative sixth transmembrane spanning domain. The transcription start sites, demonstrated by primer extension analysis, lie 618 and 621 base pairs upstream of the methionine initiation codon. Near these putative transcription start sites, we found a TATA-like motif and a potential SP-1 binding site at about 30 and 65 base pairs, respectively. We also found other known binding sites of transcription regulating factors, such as AP 1, AP-2, GATA-1, Myb, nucleofactor-interleukin 6 binding consensus sequence, and an acute phase reactant-responsive element. No estrogen-responsive element was observed except three half-palindromic estrogen-responsive element motifs. Our findings of the oxytocin receptor gene structure should help to elucidate the mechanism by which the gene expression is induced drastically at parturition in the uterus and how the gene is regulated in other organs such as the mammary gland or central nervous system. PMID- 7798246 TI - Molecular model of the extracellular lectin-like domain in CD69. AB - CD69 is described as a T cell activation antigen, but the ligand and physiological function of CD69 are currently unknown. The sequence of the extracellular domain of CD69 shows some similarity with that of calcium-dependent (C-type) lectins. Using comparative computer modeling and inverse folding calculations, we have generated and analyzed a detailed three-dimensional model of the extracellular domain of CD69 based on the crystal structure of the mannose binding protein. The sequence of CD69 appears to be highly compatible with the C type lectin fold, and assessment of the model using inverse folding calculations suggests its overall correctness. Compared with mannose binding protein and the selectins, CD69 displays significant deletions in loop regions. In addition, residues that form conserved calcium binding sites found in the C-type lectin family are not conserved in CD69. This suggests the presence of structural features in CD69 that depart from some of the conserved motifs seen in two crystal structures of C-type lectins. The CD69 model shows cavity-shaped hydrophobic regions surrounded by charged residues. One of these cavities is proximal to a potential low affinity calcium binding site and may be implicated in specific interactions with ligands. PMID- 7798247 TI - Annexin IV inhibits calmodulin-dependent protein kinase II-activated chloride conductance. A novel mechanism for ion channel regulation. AB - Ca(2+)-activated Cl- current (ICl,Ca) in colonic T84 cells is inhibited by the specific peptide inhibitor of Ca2+/calmodulin-dependent kinase II (CaM KII). Annexin IV, a Ca(2+)-dependent phospholipid binding protein also inhibits Ca(2+) dependent anion current activation (Kaetzel, M.A., Chan, H.-C., Dubinsky, W.P., Dedman, J.R., and Nelson, D.J. (1994) J. Biol. Chem. 269, 5297-5302). Intracellular injection of antibodies against annexin IV enhances current activation; this activation is inhibited by the peptide inhibitor of CaM KII. Intracellular application of autonomously active CaM KII in the presence of ATP induced a Cl- current similar to that activated by the Ca2+ ionophore A23187. Current activation by the exogenous kinase was completely inhibited in the presence of purified annexin IV. In vitro, annexin IV does not inhibit CaM KII activity nor does it act as a substrate for CaM KII. Thus, it appears that annexin IV inhibits phosphorylation-dependent anion conductance activation by preventing CaM KII-ion channel interaction rather than by direct interaction with the enzyme itself. These findings suggest a novel mechanism by which Ca(2+) dependent membrane binding proteins, cytoplasmic kinases, and ion channels interact to regulate membrane conductance. The characterization of unique channel regulatory pathways in Cl- transporting epithelia may identify potential avenues of alternate therapy to compensate for the loss of functional Cl- channels in the disease of cystic fibrosis. PMID- 7798248 TI - Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein. AB - Latent transforming growth factor-beta (TGF-beta)-binding protein (LTBP) is a component of the latent TGF-beta complex in human platelets. LTBP is composed of two different cysteine-rich repeat sequences, i.e. epidermal growth factor (EGF) like repeats and a repeat containing 8 cysteine residues. The overall structure of LTBP is similar to those of the microfibrillar proteins fibrillin-1 and fibrillin-2. Here we report the identification of a novel protein termed LTBP-2, which is structurally related to LTBP. cDNA for LTBP-2 was obtained from human foreskin fibroblast cDNA libraries using a fragment of the LTBP cDNA as a probe. LTBP-2 is composed of 20 EGF-like repeats and four copies of the 8-cysteine repeat. The amino acid sequence of LTBP-2 is 41% identical to that of LTBP and 25% identical to that of fibrillin-1. LTBP-2 is synthesized as a 240-kDa protein by human foreskin fibroblasts and also by COS cells transfected with the isolated LTBP-2 cDNA. Similar to LTBP, a considerable part of LTBP-2 was found to be associated with extracellular matrix. Co-transfection of cDNAs for LTBP-2 and TGF beta 1 revealed that LTBP-2 forms a high molecular weight complex with the TGF beta 1 precursor. The LTBP-2 gene was assigned to chromosome 14q24. These results indicate that different forms of latent TGF-beta complexes occur and suggest that the different associated proteins may function to target the complexes to specific sites. PMID- 7798249 TI - Tyrosine kinases regulate the cytoskeletal attachment of integrin alpha IIb beta 3 (platelet glycoprotein IIb/IIIa) and the cellular retraction of fibrin polymers. AB - Integrins promote cell-substratum and cell-cell adhesion by acting as transmembrane linker molecules between extracellular adhesion proteins and the actin-rich cytoskeleton. The integrin alpha IIb beta 3 (platelet glycoprotein IIb/IIIa) is essential for platelet spreading, aggregation, fibrin clot retraction, and for the transduction of extracellular signals. We examined the effect of the specific tyrosine kinase inhibitor herbimycin A on integrin and cytoskeletal-mediated events in thrombin-stimulated platelets. Incubation of washed platelets for 24 h with herbimycin A (5 microM) abolished the thrombin stimulated cytoskeletal enzyme activity of pp60c-src in parallel with a reduction in the tyrosine phosphorylation of multiple platelet proteins, as assessed with anti-phosphotyrosine immunoblots. However, thrombin-induced activation of protein kinase C and the production of thromboxane A2 were not altered by herbimycin A. Despite the absence of cytoskeletal pp60c-src enzyme activity, platelet shape change, aggregation, and serotonin release were unaltered following platelet stimulation with thrombin (0.05-1.0 unit/ml). Herbimycin A-treated platelets also demonstrated normal platelet aggregation in response to collagen (5 micrograms/ml), ionophore A23187 (2 microM), and ADP/adrenaline (10 microM each). However, the ability of herbimycin A-treated platelets to retract fibrin gels was significantly reduced. This defect in clot retraction was associated with reduced incorporation of integrin alpha IIb beta 3 into the cytoskeletal fraction of thrombin-aggregated platelets. Our studies suggest that tyrosine kinases in platelets regulate the cytoskeletal attachment of alpha IIb beta 3, as an essential process for the transmission of cellular contractile forces to fibrin polymers. PMID- 7798250 TI - Structural requirements for inducible shedding of the p55 tumor necrosis factor receptor. AB - Induced shedding of the p55 tumor necrosis factor receptor (p55-R) was previously shown to be independent of the amino acid sequence properties of the intracellular domain of this receptor. We now find it also independent of the sequence properties of the transmembrane domain and of the cysteine-rich region that constitutes most of the extracellular domain of the receptor. The shedding is shown to depend solely on the sequence properties of a small region within the spacer that links the cysteine-rich region in the extracellular domain to the transmembrane domain. Detailed tests of effects of mutations in the spacer on the shedding indicate that the process is independent of the amino acid side-chain identity in this region except for a limited dependence on the identity of 1 residue (Val-173), located downstream to the putative major cleavage site of the receptor. It is strongly affected, however, by some mutations that seem to change the conformation of the spacer region. These findings suggest that a short amino acid sequence in the p55-R is essential and sufficient for its shedding and that the shedding is mediated either by a protease with limited sequence specificity or by several different proteases that recognize different amino acid sequences, yet it strictly depends on some conformational features of the cleavage region in the receptor. PMID- 7798251 TI - Functional expression of the human angiotensinogen gene in transgenic mice. AB - The renin-angiotensin system is a major determinant of arterial pressure and volume homeostasis in mammals through the actions of angiotensin II, the proteolytic digestion product of angiotensinogen. Molecular genetic studies in several human populations have revealed genetic linkage between the angiotensinogen gene and both hypertension and increased plasma angiotensinogen. Transgenic mice were generated with a human angiotensinogen genomic clone to develop an animal model to examine tissue- and cell-specific expression of the gene and to determine if overexpression of angiotensinogen results in hypertension. Human angiotensinogen mRNA was expressed in transgenic mouse liver, kidney, heart, adrenal gland, ovary, brain, and white and brown adipose tissue and, in kidney, was exclusively localized to epithelial cells of the proximal convoluted tubules. Plasma levels of human angiotensinogen were approximately 150 fold higher in transgenic mice than that found normally in human plasma. The blood pressure of mice bearing the human angiotensinogen gene was normal but infusion of a single bolus dose of purified human renin resulted in a transient increase in blood pressure of approximately 30 mm Hg within 2 min. These results suggest that abnormalities in the angiotensinogen gene resulting in increased circulating levels of angiotensinogen could potentially contribute in part to the pathogenesis of essential hypertension. PMID- 7798252 TI - The mechanical properties of actin gels. Elastic modulus and filament motions. AB - To address large discrepancies reported in the literature, the viscoelastic properties of gels formed by purified actin filaments have been measured by five different techniques and five different instruments using actin preparations purified separately in four different laboratories. These measurements consistently showed that the elastic shear modulus of 2 mg/ml F-actin is on the order of several hundred pascals, and depends very strongly on the length of the filaments and on the history of the sample prior to measurement. Shortening of actin filaments with gelsolin and mechanical perturbations reduce the shear modulus to low values identical to some reported in the literature, indicating that such perturbations account for low shear moduli and poor responsiveness to filament modifying treatments reported previously. The structures of individual actin filaments within gels very similar or identical to those studied rheometrically were also examined by dynamic light scattering and fluorescence microscopy. Dynamic light scattering data were analyzed by a new method to confirm that actin filaments have no stable associations with each other and fluctuate in solution at a rate governed by the filament bending modulus or persistence length, determined to be approximately 10 microns. Fluorescence microscopy confirmed that applying even small shear stresses to F-actin can orient and rupture the filaments, and that in a minimally perturbed viscoelastic gel, long actin filaments are free to diffuse within a limit of constraints formed by their neighbors. These findings confirm that relatively isotropic F actin networks are sufficiently strong to stabilize cells. PMID- 7798253 TI - Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2. AB - Sequestration of m2 receptors (muscarinic acetylcholine receptor m2 subtypes), which was assessed as loss of N-[3H]methylscopolamine ([3H]NMS) binding activity from the cell surface, was examined in COS 7 and BHK-21 cells that had been transfected with expression vectors encoding the m2 receptor and, independently, vectors encoding a G protein-coupled receptor kinase (GRK2) (beta-adrenergic receptor kinase 1) or a GRK2 dominant-negative mutant (DN-GRK2). The sequestration of m2 receptors became apparent when the cells were treated with 10(-5) M or higher concentrations of carbamylcholine. In this case, approximately 40% or 20-25% of the [3H]NMS binding sites on COS 7 or BHK-21 cells, respectively, were sequestered with a half-life of 15-25 min. In cells in which GRK2 was also expressed, the sequestration became apparent in the presence of 10( 7) M carbamylcholine. Approximately 40% of the [3H]NMS binding sites on both COS 7 and BHK-21 cells were sequestered in the presence of 10(-6) M or higher concentrations of carbamylcholine. When DN-GRK2 was expressed in COS 7 cells, the proportion of [3H]NMS binding sites sequestered in the presence of 10(-5) M or higher concentrations of carbamylcholine was reduced to 20-30%. These results indicate that the phosphorylation of m2 receptors by GRK2 facilitates their sequestration. These results are in contrast with the absence of a correlation between sequestration and the phosphorylation of beta-adrenergic receptors by the GRK2 and suggests that the consequences of phosphorylation by GRK2 are different for different receptors. PMID- 7798254 TI - Thapsigargin and di-tert-butylhydroquinone induce synergistic stimulation of DNA synthesis with phorbol ester and bombesin in Swiss 3T3 cells. AB - The specific inhibitors of the endoplasmic reticulum Ca2+ pump, thapsigargin and 2,5-di-tert-butylhydroquinone (DBHQ), stimulated reinitiation of DNA synthesis in synergy with either phorbol 12,13-dibutyrate or bombesin in Swiss 3T3 cells. Maximum stimulation was achieved at 0.5 nM thapsigargin and 7.5 microM DBHQ. Kinetics of [3H]thymidine incorporation were consistent with exit from G0 and entry into S phase. Autoradiography of labeled nuclei showed that the increase in [3H]thymidine incorporation was due to an increase in the proportion of cells entering into DNA synthesis. Down-regulation or selective inhibition of protein kinase C abolished this synergistic stimulation of DNA synthesis. Thapsigargin and DBHQ did not potentiate protein kinase C-mediated signals such as direct phosphorylation of myristoylated alanine-rich C-kinase substrate, activation of mitogen-activated protein kinase, and tyrosine phosphorylation of bands 110,000 130,000 and 70,000-80,000. Thapsigargin and DBHQ caused a marked reduction in the ability of bombesin to induce a rapid and transient increase in intracellular Ca2+ via depletion of total cellular Ca2+, measured by 45Ca2+ content. The synergistic stimulation of DNA synthesis by DBHQ and phorbol 12,13-dibutyrate was dependent on a high concentration of extracellular Ca2+ (ED50 = 410 microM) and was preferentially inhibited by the inhibitor of Ca2+ influx econozole. This suggests a role for Ca2+ entry in growth control. This is the first time that either thapsigargin or DBHQ has been shown to stimulate the reinitiation of DNA synthesis in any target cell. PMID- 7798256 TI - Identification of an internal topogenic signal sequence in human Band 3, the erythrocyte anion exchanger. AB - The insertion of Band 3, the human erythrocyte anion exchanger, into microsomal membranes was studied in an in vitro reticulocyte lysate translation system. Band 3 consists of a 43-kDa amino-terminal cytosolic domain and a carboxyl-terminal 52 kDa membrane domain containing up to 14 transmembrane segments with a single N glycosylation site at Asn-642. Insertion of truncated Band 3 molecules into microsomal membranes was assayed by glycosylation, resistance to alkaline extraction, and tryptic removal of the cytosolic domain. Truncations containing either the first four or the last eight putative transmembrane segments were stably integrated into microsomes showing that an intact membrane domain was not required for membrane integration. Furthermore, the extracytosolic domain following the seventh transmembrane segment was properly translocated across the microsomal membrane and glycosylated whether the seventh transmembrane segment was the first, last, or the only transmembrane segment in the construct. The ability of the entire membrane domain, the truncated domain beginning with the seventh transmembrane segment, or the seventh transmembrane segment to insert into microsomes was dependent on the presence of the signal recognition particle receptor. The seventh transmembrane segment in Band 3 therefore has the topogenic properties of an internal signal sequence. PMID- 7798255 TI - Molecular cloning and site-directed mutagenesis of glutathione S-transferase from Escherichia coli. The conserved tyrosyl residue near the N terminus is not essential for catalysis. AB - Glutathione S-transferase (GST) was purified from Escherichia coli K-12, and its N-terminal sequence was determined to be MKLFYKPGAXSLAS. The gene encoding this sequence was cloned and mapped at 1731-1732 kilobases on the E. coli gene map. It encoded a polypeptide of 201 amino acid residues with a calculated molecular weight of 22,860. The overexpressed product of the gene was confirmed to have GST activity toward 1-chloro-2,4-dinitrobenzene and ethacrynic acid and GSH-dependent peroxidase activity toward cumene hydroperoxide. The relative molecular mass of the gene product was determined to be 40,000 by gel chromatography and 25,000 by SDS-polyacrylamide gel electrophoresis, indicating a homodimeric structure. The deduced amino acid sequence was 54% identical with that of Proteus mirabilis GST. Although the homologies between the GSTs from E. coli and mammals were low, many of the residues assigned to be important for the enzymatic function or structure in mammalian cytosolic GSTs were found to be conserved in E. coli GST. Therefore, E. coli GST is considered to have diverged from the same ancestor with other cytosolic GSTs. A specific tyrosyl residue in the vicinity of the N terminus is conserved in all of the known cytosolic GSTs and has been shown to function as a catalytic residue in alpha, mu, and pi class GSTs from mammals. Although Tyr5 in E. coli GST appeared to be the counterpart of the catalytic residue, its replacement with phenylalanine did not significantly affect the enzymatic activity. Therefore, this apparently conserved tyrosyl residue is not essential for catalytic activity in E. coli GST. PMID- 7798257 TI - Overlapping Egr-1 and Sp1 sites function in the regulation of transcription of the mouse thrombospondin 1 gene. AB - We have evaluated the basis for the constitutive and serum-regulated expression of the mouse thrombospondin (TSP) gene in both transiently and stably transfected NIH-3T3 cells. Experiments with deleted and mutated mouse promoter/CAT constructs and gel mobility assays demonstrated that an Egr-1 binding site in the proximal promoter, flanked by overlapping GC boxes and an adjacent GC-rich region, functioned to positively regulate the constitutive activity of the gene. These motifs, and their cognate transcription factors, appear to act in concert, with partial redundancy, so that discrete mutations were only partially effective in reducing transcriptional activity. The Egr-1 site corresponds in position to an NF-Y binding site which functions synergistically with a distal serum-response element to mediate the serum response of the human TSP1 gene. However, neither the Egr-1 motif nor the surrounding proximal promoter region upstream from the TATA box participates in the serum response of mouse TSP1. These experiments add support to the growing realization that similar physiologic responses of homologous genes in mouse and man need not utilize similarly placed cis-acting elements. PMID- 7798258 TI - Mitogenicity and transforming activity of the insulin-like growth factor-I receptor with mutations in the tyrosine kinase domain. AB - We have investigated the effect of mutations in tyrosines 1131, 1135, and 1136 of the human insulin-like growth factor-I receptor (IGF-IR) on the growth and transformation of mammalian cells. We have used for this purpose R- cells, which are 3T3-like fibroblasts derived from mouse embryos with a targeted disruption of the IGF-IR genes. These cells have no IGF-IR, do not grow in serum-free medium supplemented with the growth factors that sustain the growth of 3T3 cells, and cannot be transformed by simian virus 40 large tumor antigen or other oncogenes. The R- cells were transfected with plasmids expressing: 1) a wild type human IGF IR cDNA; 2) a receptor with a triple mutation in the above mentioned tyrosines; and 3) receptors with single tyrosine mutations. Cells expressing the wild type or the single tyrosine mutants Y1 (Y1131F) and Y2 (Y1135F) grew in serum-free medium supplemented solely with IGF-I. Cells expressing the triple tyrosine mutant YF or the single mutant Y3 (Y1136F) failed to grow in response to IGF-I only. All mutants, though, failed to form colonies in soft agar, indicating that a fully functional IGF-IR is more critical for anchorage-independent growth than for monolayer growth. The triple mutant expression plasmid also functioned as a dominant negative, inhibiting the growth of wild type cells transformed by the simian virus tumor antigen. PMID- 7798259 TI - Enhancer activity of upstream hypersensitive site 2 of the chicken beta-globin cluster is mediated by GATA sites. AB - Upstream of the chicken beta-globin gene cluster are four DNase I-hypersensitive sites (HS1-4). Hypersensitive sites located upstream of the mammalian beta-globin clusters have enhancer activity and mediate position-independent gene expression. In contrast, a region inside the chicken cluster has enhancer activity and mediates position-independent expression. Here we investigate the function of the chicken upstream sites, which are different from the mammalian ones in sequence, number, and distance from the genes. Each was tested for its effect on reporter gene expression in transfected primary erythroid cells. HS2 and HS3 (4.4 and 6.4 kilobases upstream of rho-globin) showed significant enhancer activity while HS1 and HS4 (1.6 and 11 kilobases upstream of rho-globin) did not. A 237-base pair region of HS2 contained the sequences necessary for enhancer activity. Proteins from erythroid extracts bound HS2 in seven different regions; six of these sites were characterized. GATA-1 bound to four of the sites. Each site contributed to the enhancer activity of HS2. Two other sequences bound proteins that may be related to Sp1 and erythroid kruppel-like factor. Surprisingly, mutations in these elements, which disrupted protein binding, did not affect enhancer activity. Thus, the observed enhancer activity of HS2 is due to the four GATA sites. The existence of multiple GATA sites in both chicken HS2 and the mammalian upstream sites may be due to evolution from a common element with preservation of only very short sequences or to convergent evolution. These observations highlight the crucial role for GATA proteins in globin regulation. PMID- 7798260 TI - Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues. AB - Bone morphogenetic protein-1 (BMP-1) is a metalloprotease purified from extracts capable of inducing ectopic bone formation. In humans, it has a domain structure similar to that of the Drosophila dorsal-ventral patterning gene-product tolloid (Tld), but is considerably shorter. Here we show that, in humans and mice, alternatively spliced transcripts encode BMP-1 and a longer protein, designated mammalian tolloid (mTld), with a domain structure identical to that of Drosophila Tld. A third alternatively spliced product, in which a novel domain is inserted near the BMP-1 C terminus, is also reported. Low levels of transcripts for mTld were found in all adult human tissues surveyed, while BMP-1 transcripts were detectable in all adult tissues except brain. This differential expression was mirrored in embryonic mouse tissues where in situ hybridization found high levels of mTld transcripts, but was unable to detect BMP-1 transcripts, in the floor plate of the neural tube of the developing central nervous system. The third alternatively spliced form was not detected in adult human tissues. In situ hybridizations found punctate signals for all three forms localized to trophoblast giant cells in 17.5-day mouse placenta, with highest levels of expression, especially for BMP-1, near the maternal interface. PMID- 7798261 TI - The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto Vav. AB - Stimulation of the T cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including the vav proto oncogene product. We now report the detection of several phosphotyrosine proteins (80, 74, and 70 kDa) from TCR-stimulated T cells that bind to the Src homology 2 (SH2) domain of proto-Vav (Vav-SH2) and co-immunoprecipitate with the proto-Vav product. Their binding to Vav-SH2 differs from that observed with SH2 domains from other proteins. None of the Vav-SH2-associated phosphoproteins bind to either of the Src homology 3 (SH3) domains of proto-Vav or to mutant Vav-SH2 proteins. The association of the phosphoproteins with Vav-SH2 requires induction of tyrosine phosphorylation of cellular proteins since proteins from lysates of herbimycin A-treated TCR-activated T cells fail to associate with Vav-SH2. Among the proteins from T cells that co-immunoprecipitate with the proto-Vav product and bind to its SH2 domain, specific antibodies identified the 70-kDa tyrosine phosphoprotein as ZAP-70, a protein tyrosine kinase (PTK) involved in TCR signal transduction. Binding of this PTK to Vav-SH2 is inhibited by a ZAP-70-specific synthetic tyrosine phosphopeptide. We suggest that ZAP-70 may function as a PTK for proto-Vav. PMID- 7798262 TI - Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. AB - Previous studies from this laboratory and others suggest that arachidonic acid and its metabolites play important roles in a variety of biological processes such as signal transduction, contraction, chemotaxis, and cell growth and differentiation. Here we studied the effect of arachidonic acid on mitogen activated protein (MAP) kinases in vascular smooth muscle cells (VSMC). Arachidonic acid activated MAP kinases in VSMC in a time- and dose-dependent manner. Nordihydroguaiaretic acid (NDGA), a potent inhibitor of the lipoxygenase system, significantly blocked the arachidonic acid-induced activation of MAP kinases, whereas indomethacin, an inhibitor of cyclooxygenase, had no effect. In VSMC, arachidonic acid was converted to 15-hydroxyeicosatetraenoic acid (15 HETE); NDGA inhibited the formation of this HETE. Exogenous addition of 15-HETE to VSMC caused stimulation of MAP kinases. Depletion of protein kinase C attenuated both the arachidonic acid- and 15-HETE-induced activation of MAP kinases in VSMC. Together these results suggest that 1) arachidonic acid activates MAP kinases in VSMC; 2) 15-HETE, a 15-lipoxygenase product of arachidonic acid, at least in part, mediates the arachidonic acid effect on MAP kinases; and 3) protein kinase C appears to be important in arachidonic acid activation of MAP kinases. Therefore, MAP kinases may play an important role in arachidonic acid signaling of VSMC growth and function. PMID- 7798263 TI - Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1. AB - Elevations in gene dosage of the transcriptional regulatory protein yAP-1 in Saccharomyces cerevisiae can elicit pronounced phenotypic increases in tolerance of a variety of drugs including the toxic heavy metal cadmium. While a large elevation in cadmium tolerance occurs in response to overproduction of yAP-1, the target genes under yAP-1 control have not yet been identified that are responsible for this increase. We show here that the YCF1 gene, encoding a likely integral membrane protein, is required for yAP-1 to exert its normal effects on cadmium tolerance. Mutant strains of yeast that lack the YCF1 gene are hypersensitive to cadmium and this hypersensitivity is epistatic to yAP-1 overexpression. YCF1 mRNA levels and the expression of a YCF1-lacZ reporter construct positively correlates with changes in YAP1 gene dosage. A set of 5' truncation derivatives of the YCF1-lacZ fusion gene identified the region from 201 to +47 as being sufficient for the yAP-1-dependent increase in expression. DNase I footprinting using a probe from this segment of the YCF1 promoter showed that bacterially-produced yAP-1 protein was capable of binding a novel DNA element we have designated the yAP-1 response element. Insertion of the yAP-1 response element upstream of a CYC1-lacZ gene fusion led to the production of beta-galactosidase in a yAP-1-dependent fashion. These data establish that an important physiological target of yAP-1 transcriptional regulation is the YCF1 structural gene. PMID- 7798264 TI - Evidence for a second receptor binding site on human prolactin. AB - The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the resulting mutants exhibit reduced bioactivity in the Nb2 cell proliferation bioassay, the mutated residues do not appear to be functionally necessary. Next, small residues surrounding the helix 1 helix 3 interface were replaced with Arg and/or Trp, the aim being to sterically hinder the second binding site. Several of these mutants exhibit only weak agonistic properties, supporting our hypothesis that the channel between helices 1 and 3 is involved in a second receptor binding site. We then analyzed the antagonistic and self-antagonistic properties of native hPRL and of several hPRLs analogs altered at binding site 1 or 2. Even at high concentrations (approximately 10 microM), no self-inhibition was observed with native hPRL; site 2 hPRL mutants self-antagonized while site 1 mutants did not. From these data, we propose a model of hPRL-PRL receptor interaction which slightly differs from that proposed earlier for the homologous human growth hormone (hGH) (Fuh, G., Cunningham, B. C., Fukunaga, R., Nagata, S., and Goeddel, D. V., and Well, J. A. (1992) Science 256, 1677-1680). Like hGH, hPRL would bind sequentially to two receptor molecules, first through site 1, then through site 2, but we would expect the two sites of hPRL to display, unlike the two binding sites of hGH, about the same binding affinity, thus preventing self-antagonism at high concentrations. PMID- 7798265 TI - The sperm acrosomal matrix contains a novel member of the pentaxin family of calcium-dependent binding proteins. AB - The sperm acrosome is a regulated secretory granule that undergoes exocytosis during fertilization. To elucidate the structural organization of the contents within the acrosome, guinea pig sperm acrosomal apical segments were isolated and mapped by two-dimensional polyacrylamide gel electrophoresis (PAGE). Although complex, the two-dimensional PAGE map was dominated by two M(r) 50,000 polypeptides (p50 and proacrosin), a M(r) 67,000 polypeptide (p67), and a M(r) 32,000 polypeptide (sp32). Proacrosin (pI > 8.0), p67, and sp32 were extracted from apical segments by 1 M NaCl. Protein p50, a relatively acidic polypeptide, was not extracted in 1 M NaCl and/or 1% Triton X-100 at 4 degrees C, but was solubilized with 6 M urea. Protein p50 was purified from the urea extract by elution from DEAE-Sephacel with 100 mM guanidine HCl and appeared homogeneous by SDS-PAGE. Antibodies to p50 were monospecific as judged by Western blot analysis. Indirect immunofluorescence indicated that p50 was restricted to the acrosomal apical segment. Incubation of apical segments at pH 7.5 in the presence of 1 mM EDTA at 37 degrees C resulted in the release of p50 into the 200,000 x g supernatant fluid, a process that was reversed by a subsequent incubation with 1.5 mM CaCl2, but not with MgCl2. The Ca(2+)-dependent reassociation of p50 with the acrosomal apical segments was reversed by the addition of 2.0 mM EGTA, indicating that p50 binding is dependent on free Ca2+ concentrations. When acrosomal matrices were purified following Triton X-100 extraction, p50 was the major component, with p67, proacrosin, and sp32 as less prominent constituents. Molecular cloning demonstrated that p50 is a unique, testis-specific member of the pentaxin family of calcium-dependent binding proteins. PMID- 7798266 TI - Apexin, an acrosomal pentaxin. AB - We report the initial biochemical characterization and the primary structure of a guinea pig sperm acrosomal pentaxin (apexin). Pentaxins are a family of penta- or decameric serum proteins that includes serum amyloid protein and C-reactive protein. Apexin consists of disulfide-linked 50-kDa subunits that give rise to an oligomeric protein. Apexin and a sperm protein related to complement receptors coelute with affinity-purified fertilin (PH-30), a potential sperm-egg membrane fusion protein. However, no evidence for a functional association of apexin with fertilin was found. Apexin is localized to the acrosome of mature guinea pig sperm and is thus the first pentaxin for which a defined intracellular localization has been reported. Whereas the C-terminal portion of apexin is clearly related to serum pentaxins, the N-terminal domain shows no strong homology to other known proteins. Northern blot analysis of different tissues revealed expression in the testis. Apexin is distinct from the pentaxins serum amyloid protein and C-reactive protein and may have evolved to perform functions other than those performed by serum pentaxins, such as intracellular protein sorting to the acrosome. PMID- 7798267 TI - The signaling pathway coupling epidermal growth factor receptors to activation of p21ras. AB - Epidermal growth factor (EGF) treatment causes autophosphorylation of the epidermal growth factor receptor (EGFR) leading to increased guanine nucleotide exchange factor (GEF; Sos) activity and enhanced formation of p21ras-GTP. The connection of the EGFR to p21ras activation can occur through binding of Grb2.Sos complexes to the EGFR or through the adaptor protein Shc via EGFR.Shc.Grb2.Sos multimeric complexes. Therefore, we investigated the importance of Shc in coupling the EGFR to activation of ras GEF (Sos). EGF treatment led to rapid tyrosine phosphorylation of Shc. Although phosphorylated EGFR can bind to both Shc and Grb2, the predominant linkage was observed between EGFR and Shc. Similarly, more Grb2 was associated with Shc than with EGFR after EGF stimulation. Immunoprecipitation of Shc from EGF-stimulated cells removed almost all EGFR-associated Grb2. Furthermore, immunodepletion of Shc proteins from membrane fractions of EGF-stimulated cells removed 93% of the ras GEF activity, whereas, precipitation of EGFR had only a small effect on ras GEF activity. These data indicate that coupling to Shc provides the major pathway linking activated EGFRs to Grb2.Sos and stimulation of the p21ras pathway. PMID- 7798268 TI - A 30-base pair element is responsible for the myeloid-specific activity of the human neutrophil elastase promoter. AB - Human neutrophil elastase (HNE), a serine protease, is expressed only in the promyelocytic stages of granulocyte maturation. We examined several regions of the promoter for transcriptional activity and report that a 30-base pair (bp) element located between -76 and -106 in the 5'-flanking region of HNE is sufficient for myeloid-specific expression of HNE. Gel shift assays using nuclear extracts from myeloid and non-myeloid cells reveal several myeloid-specific complexes binding to the 30-bp element. Examination of DNA-protein interactions shows that at least two myeloid-specific proteins of 38 and 55 kDa bind to this element. DNase I protection analysis reveals two distinct footprints between -80 to -91 and -94 to -104 within this element. Transient expression studies using deletion constructs of the HNE 5'-flanking region show that the 30-bp element is active in myeloid cells K 562 and U 937 but not in HeLa cells. Internal deletion of this element results in a 60-85% loss of promoter activity in myeloid cells. Additional functional studies also show that a 19-bp region between -112 and -131 contributes to transcriptional activity of the elastase promoter as well. PMID- 7798269 TI - Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity. AB - In an effort to clarify the regulation of distribution and actions of transforming growth factor (TGF)-beta in bone, TGF-beta 1 binding to extracted bone matrix proteins and the influence of such binding on TGF-beta 1 actions were examined. In-gel binding of 125I-TGF-beta 1 using extracts from mineralized bovine bone matrix demonstrated that 125I-TGF-beta 1 was almost exclusively bound to a proteoglycan, decorin. The binding was via the core protein of decorin. Scatchard analysis of the binding of 125I-TGF-beta 1 to immobilized decorin purified from osteoblastic MC3T3-E1 cell conditioned medium revealed that there were two specific binding sites with high and low affinities for TGF-beta 1 (Kd = 0.3 and 5 nM, respectively). The addition of decorin along with TGF-beta 1 enhanced the inhibitory effect of TGF-beta 1 on MC3T3-E1 cell proliferation. Decorin in itself did not affect their proliferation. These cells possessed types I and II TGF-beta receptors and betaglycan, and the addition of decorin increased the binding of 125I-TGF-beta 1 to all these receptors. These results demonstrate that the core protein of decorin specifically binds TGF-beta 1 with high affinities and that the binding of TGF-beta 1 to decorin increases TGF-beta 1 binding to its receptors and enhances its bioactivity. Because TGF-beta is released by bone resorption along with matrix proteins, including decorin, and because it stimulates the synthesis of these proteins, it is suggested that the binding and enhancement of the activities of TGF-beta by decorin may play a role in maintaining bone formation during bone remodeling process. PMID- 7798270 TI - Exon 11 enhances insulin binding affinity and tyrosine kinase activity of the human insulin proreceptor. AB - Data presented here show that there are significant differences in the insulin binding affinity and the tyrosine kinase activity of the insulin proreceptor isoforms which contain or lack exon 11. The exon 11(+) proreceptor does not show significant variations from the mature processed insulin receptor and has only a 3- to 4-fold reduced affinity for insulin. In contrast, the exon 11(-) proreceptor showed a markedly reduced insulin binding (25- to 50-fold less) when assayed on intact cells. Upon solubilization of the cells, exon 11(-) proreceptor bound insulin with somewhat higher affinity. Mild trypsin treatment of the cells expressing either isoform of the insulin proreceptor restored insulin binding to near-normal levels. Analysis of tyrosine kinase activity revealed that the exon 11(+) proreceptor required somewhat higher concentrations of insulin than the mature processed receptor to achieve maximal autophosphorylation. The exon 11(-) proreceptor failed to fully phosphorylate even at 10(-6) M insulin. Thus, the presence or absence of this short sequence of 12 amino acids affects the folding and/or conformation of the proreceptor so as to confer altered binding of insulin. We suggest that in the absence of exon 11 the proreceptor assumes a strained conformation that disrupts the insulin binding site. Cleavage of the proreceptor at the alpha-beta-subunit junction then allows the alpha-subunit to achieve its normal binding conformation. PMID- 7798271 TI - ETS transcription factors regulate the expression of the gene for the human mitochondrial ATP synthase beta-subunit. AB - Elements responsible for the transcriptional activity of the human ATP synthase beta-subunit (ATPsyn beta) gene promoter have been studied through transient expression in HepG2 hepatoma cells of a CAT gene connected with various 5' deletion mutants of the 5'-flanking region. Promoter activity was mostly dependent upon a single CCAAT motif as well as a nearby Ets domain binding region. This last region contains two sites that bind Ets-related proteins present in liver nuclear extracts as well as recombinant purified Ets-1 protein. The ATPsyn beta promoter was trans-activated by Ets-1 and Ets-2 expression vectors, and this effect was lost when the Ets binding region was deleted. The Ets binding region of the ATPsyn beta promoter increased basal expression and conferred Ets-1- and Ets-2-dependent trans-activation to the herpes symplex thymidine kinase minimal promoter. A double-point mutation of the main Ets binding site, which suppresses Ets binding, blocks Ets-dependent trans activation. It is concluded that the gene for the mitochondrial ATPsyn beta is a target of transcriptional activation by members of the Ets family of transcription factors. It is suggested that Ets transcription factors may be involved in the enhanced expression of the ATPsyn beta gene in highly proliferating cells and in the coordinate transcription of nuclear genes for mitochondrial proteins. PMID- 7798272 TI - Topoisomerase III, but not topoisomerase I, can support nascent chain elongation during theta-type DNA replication. AB - Topoisomerase III, but not topoisomerase I, could, in the absence of DNA gyrase, support bidirectional DNA replication in an oriC plasmid DNA replication system reconstituted with purified proteins. The initial rate of DNA synthesis and the efficiency of nascent chain elongation showed that topoisomerase III-stimulated DNA replication was as efficient as gyrase-stimulated DNA replication. In addition, topoisomerase III was also able, in the absence of DNA gyrase, to decatenate the replicating daughter DNA molecules to form monomer product. Thus, of the four topoisomerases in Escherichia coli, three, topoisomerases III and IV and DNA gyrase, can support nascent chain elongation, whereas only two, topoisomerases III and IV, can topologically resolve the daughter molecules. PMID- 7798274 TI - Characterization of human Gadd45, a p53-regulated protein. AB - GADD45 (growth arrest and DNA damage) is a DNA-damage-inducible gene regulated in part by the tumor suppressor p53. A role in negative growth control has recently been suggested based on significant (more than 75%) reduction of colony formation following over expression of Gadd45. To better understand the role of Gadd45, we have developed specific rabbit and murine antibodies raised against the human recombinant protein. Using these antibodies, we have found that in ML-1 cells Gadd45 is predominantly a nuclear protein. MyD118, a protein induced by terminal differentiation sharing 57% homology with Gadd45, does not cross-react with any of the antibodies produced. As expected, the induction of Gadd45 protein by ionizing radiation (IR) was also found to be dependent on a wild type p53 phenotype. Interestingly, WI-L2-NS, a human lymphoid cell line, showed very high basal levels of Gadd45 mRNA and protein in addition to a high constitutive level of a mutated p53 protein. In this cell line, the high levels of GADD45 did not inhibit cellular growth in spite of the fact that no mutations were found in GADD45 sequence. These results indicate that some cell line(s) can tolerate high levels of Gadd45 and abrogate its growth suppression function. PMID- 7798273 TI - Arginine becomes an essential amino acid after massive resection of rat small intestine. AB - We compared effects of feeding arginine- and/or proline- deficient diets (-Arg, Pro, and -Arg, Pro) with those of a complete diet (Complete) in rats whose small intestine had been massively resected. After 4 weeks, the rats fed -Arg and -Arg, Pro lost weight (a mean of 28 and 32 g, respectively), whereas those fed Complete and -Pro gained 80 and 58 g, respectively. The average nitrogen balance was about 117,100, -20 and -14 mg/day for Complete, -Pro, -Arg, and -Arg, Pro diets, respectively. The concentration of arginine in skeletal muscle was about 310, 330, 91, and 65 nmol/g for Complete, -Pro, -Arg, and -Arg, Pro, respectively; while plasma arginine concentration averaged 95, 107, 56, and 46 microM, respectively. The weight loss, the negative nitrogen balance, and the markedly reduced arginine concentration in the muscle observed in rats fed -Arg and -Arg, Pro clearly indicate that arginine becomes a strictly essential amino acid in the rats with massive resection of the small intestine. However, sufficient proline can be synthesized from arginine in tissues such as the liver and kidney in the absence of the small intestine. Plasma glutamine, citrulline in the muscle and plasma, urinary excretion of orotic acid and nitrate (to assess nitric oxide formation from arginine) were also measured, and the changes in these metabolites are discussed. PMID- 7798275 TI - Novel approach to molecular cloning and polynucleotide synthesis using vaccinia DNA topoisomerase. AB - Construction of chimaeric DNA molecules in vitro relies traditionally on two enzymatic steps catalyzed by separate protein components. Site-specific restriction endonucleases are used to generate linear DNAs with defined termini that can then be joined covalently at their ends via the action of DNA ligase. A novel approach to the synthesis of recombinant DNAs exploits the ability of a single enzyme, vaccinia DNA topoisomerase, to both cleave and rejoin DNA strands with extreme specificity at each step. Placement of the CCCTT cleavage motif for vaccinia topoisomerase near the end of a duplex DNA permits efficient generation of a stable, highly recombinogenic protein-DNA adduct that can religate only to acceptor DNAs that contain complementary single-strand extensions. Linear DNAs containing CCCTT cleavage sites at both ends (bivalent substrates) can be activated by topoisomerase and inserted into a plasmid vector in a simple and rapid in vitro procedure that is especially well suited to the molecular cloning of polymerase chain reaction-amplified DNAs. Activation of polyvalent (e.g. branched) DNA substrates by topoisomerase offers a potentially powerful method for the synthesis of two- and three-dimensional polynucleotide networks. PMID- 7798276 TI - Single amino acid changes alter the repair specificity of Drosophila Rrp1. Isolation of mutants deficient in repair of oxidative DNA damage. AB - Drosophila Rrp1 has several tightly associated enzymatic activities, including double-strand DNA 3'-exonuclease, apurinic/apyrimidinic endonuclease, 3' phosphatase, and 3'-phosphodiesterase. The carboxyl-terminal third of Rrp1, homologous to Escherichia coli exonuclease III, is sufficient to repair oxidative and alkylation-induced DNA damage in vivo. Using a screen for partial complementation of repair-deficient E. coli, we isolated three mutants of the nuclease domain of Rrp1: T462A, K463Q, and L484P, that protect against methyl methanesulfonate (MMS)-induced but not t-BuO2H-induced DNA damage. Thr-462 and Lys-463 are highly conserved residues found in a cluster of 5 conserved amino acids (LQETK), while Leu-484 is poorly conserved. Gln-460 Glu-461, Thr-462, and Lys-463 and Leu-484 were altered by site-directed mutagenesis using a plasmid including the entire Rrp1 gene and mutant proteins were purified. Mutants of the three residues Glu-461, Thr-462, and Lys-463 demonstrate 8-200-fold lower phosphodiesterase specific activity than wild-type Rrp1. E461A has a 30-fold reduction in AP endonuclease and is MMS-sensitive, but all other mutants have near-normal AP endonuclease and are MMS-resistant. Glu-461 appears to be essential for the nuclease function for Rrp1. Lys-463 and, to a lesser extent, Thr-462 influence the substrate specificity of the Rrp1 nuclease. PMID- 7798278 TI - In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression. AB - The in vivo isomerization of all-trans- and 9-cis-retinoic acids (RAs) was evaluated by high performance liquid chromatography after oral administration to rats. All-trans (2 ng/ml)- and 13-cis (1.8 ng/ml)-RAs, but not 9-cis-RA, were detected in the serum of normal rats. When an excess of either all-trans-RA or 9 cis-RA (100 micrograms/rat) was intragastrically administered to the retinoid depleted rats, a rapid isomer exchange between 9-cis- and all-trans-RAs along with appearance of the administered RA occurred shortly after the dose (30 min). RA rapidly isomerized when an excess of either all-trans- or 9-cis-RA (1 mg/rat) was administered to normal rats. To examine whether the isomerized RAs elicit biological actions in vivo, the induction of target genes-[cellular retinol binding protein type II (CRBP II) for 9-cis-RA and all-trans-retinoic acid receptor beta (RAR beta) for 9-cis- and all-trans-RAs] was determined. The degree of induction of the two genes did not differ 4 h after administration of either 9 cis-RA or all-trans-RA. However, unlike all-trans-RA, the RAR-specific synthetic retinoids did not induce the CRBP II gene. These results suggested that the apparent actions of 9-cis- and all-trans-RAs on gene expression in vivo may be mediated to some extent by the converted stereoisomer. PMID- 7798277 TI - Evidence for the uptake of a vitamin D analogue (OCT) by a human carcinoma and its effect of suppressing the transcription of parathyroid hormone-related peptide gene in vivo. AB - The present study was undertaken to clarify the pharmacokinetics of 22-oxa-1,25 dihydroxyvitamin D3 (22-oxa-1,25-(OH)2D3, OCT), a vitamin D3 analogue with little calcemic activity, and its effect on the transcription of parathyroid hormone related peptide (PTHRP) gene in nude mice bearing a human carcinoma (FA-6) associated with humoral hypercalcemia. FA-6 tumor expressed vitamin D receptor (VDR) mRNA, and its nuclear extract contained a specific and saturable 1,25 (OH)2D3 binding activity. Although [3H]OCT administered intravenously into FA-6 tumor-bearing nude mice was cleared from the circulation more rapidly than [3H]1,25-(OH)2D3, the uptake of [3H]OCT into the tumor tissue, relative to the radioactivity in the circulation, was greater than that of [3H]1,25-(OH)2D3. Intravenous or oral administration of OCT reduced the steady-state levels of PTHRP mRNA in FA-6 tumor, and nuclear run-off assays demonstrated that the effect of OCT on PTHRP gene expression occurred at a transcriptional level. RNase mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were down-regulated by OCT. Finally, OCT exerted a preventive as well as therapeutic effect on cancer-associated hypercalcemia with a marked prolongation of the survival time in tumor-bearing animals. These results suggest that OCT is effectively taken up by a VDR-positive human carcinoma in vivo and has a therapeutic potential for cancer-associated hypercalcemia through suppression of PTHRP gene transcription. PMID- 7798279 TI - Drosophila kinesin motor domain extending to amino acid position 392 is dimeric when expressed in Escherichia coli. PMID- 7798280 TI - Two strategies of transferring from sit-to-stand; the activation of monoarticular and biarticular muscles. AB - In this study, two different strategies of rising from a chair were compared, using integrated biomechanical and electromyographic analyses. Nine healthy subjects were instructed to rise using two different strategies: natural sit-to stand transfer (NSTS) and a sit-to-stand transfer with full flexion of the trunk (FSTS). Sagittal kinematics and ground reaction forces were registered. Muscle activity of nine muscles of the right leg were recorded by means of surface EMG. All signals were synchronized at seat-off. The results show that no differences occur between the kinematics of knee and ankle, whereas the hip flexion is, as expected, higher during FSTS. The higher moment about the knee during NSTS is shifted to proportionally higher moments about the hip and ankle during FSTS. It is mainly the differences in the EMG-levels of the biarticular hip and knee muscles which might explain the differences in net moment. These results are in accordance with a theory about a particular role of biarticular muscles. On the other hand, the shift from knee to ankle cannot be associated with a particular increase in activity of the biarticular m.gastrocnemius. It is hypothesized that about the ankle, control of stability is preferred over movement control. An important conclusion for rehabilitation medicine is that a lower net moment about the knee in FSTS does not automatically imply that this reduces the load on the knee extensors. PMID- 7798281 TI - Mechanical behavior of damaged trabecular bone. AB - The mechanical behavior of damaged trabecular bone may play a role in the etiology of age-related spine fractures since damaged bone exists in and may weaken the elderly vertebral body. To describe some characteristics of damaged trabecular bone, we measured the changes in modulus and strength that occur when bovine trabecular bone is loaded in compression to various strains beyond its elastic range. Twenty-three reduced-section specimens, taken from 17 different bones, were loaded from 0-X-0-9% strain, where X was one of four strains: 1.0% (n = 7), 2.5% (n = 6), 4.0% (n = 5), or 5.5% (n = 5). We found that modulus was reduced for all applied strains, whereas strength was reduced only for strain levels > or = 2.5%; the percentage changes in modulus and strength were independent of Young's modulus but were highly dependent on the magnitude of the applied strains; modulus was always reduced more than strength; and simple statistical models, using knowledge of only the applied strains, predicted well the percentage reductions in modulus (r2 = 0.97) and strength (r2 = 0.74). The modulus reductions reported here are in qualitative agreement with those for cortical bone in tensile loading, supporting the concept that the damage behaviors of cortical and trabecular bone are similar for low strains (< or = 4.0%). In addition, because modulus was always reduced more than strength, damaged trabecular bone may be stress protected in vivo by redistribution of stresses to undamaged bone. PMID- 7798282 TI - Pressure development within a sac-type pneumatically driven ventricular assist device. AB - Intrinsic features of the pumping process of a pneumatically driven ventricular assist device (VAD) and the effects of different types of pneumatic drivers upon its performance were investigated in vitro by analysing the pressure distributions within the device and the motions of the prosthetic valves. It was found that the stretching of the flexible, elastic diaphragm in both late systole and diastole initiates a pressure oscillation which directly affects the timing of the pumping process. The timing was also found to be dependent on the length and stiffness of the cannulae which link the VAD to the model circulation system. During the stretch-induced oscillation in late systole, the VAD housing experiences partial collapse due to fluid momentum effects, which tends to increase the effective stroke volume of the device, and reduce the amplitude of the pressure oscillation. Reducing the rising (falling) rate of driving pressures (dpd/dt) may not necessarily reduce the maximum rate of change of the blood chamber pressure (dpch/dtmax) but may upset the stability of the pumping process. This is because a minimum dpch/dtmax exists, which is determined by the stretch induced oscillation. In order to minimize dpch/dtmax and to provide the device with a stable working condition, dpd/dt should match the dpch/dtmax. PMID- 7798283 TI - Compliance of normal, dystrophic and transplanted mouse muscles. AB - Parallel and series compliances have been studied in extensor digitorum longus (fast) and soleus (slow) muscles in normal (strain C57BL/10) and dystrophic (strain mdx) mice, and in muscles regenerated after transplantation. Resting elasticity was analysed by measuring the tension-length relationship in unstimulated muscles. Passive tension is larger in mdx and in transplanted muscles than in their normal controls: at 1.15L0, passive tension is 0.12P0 in controls, 0.32P0 in mdx, and 0.40P0 in transplanted muscles. The differences are statistically significant. This indicates that passive tension is mainly determined by the amount of connective tissue. The stress-strain relationship of the series compliance was analysed by the method of isotonic releases during tetani. It is adequately described by a single exponential equation, with a rate constant of about 8P0/P. No difference was found between the various muscles studied. Extension of the series compliance at P0 is 0.02L0. Compliance is about 3% (L0/P0) at 0.2P0, and is not significantly different from zero at P0. Series compliance is thus very low in mouse muscles, substantially lower than in frog and rat muscles. Consequently, it can be neglected in studies of whole mouse muscle in which tension is higher than 0.4P0. PMID- 7798284 TI - A model of foot placement during gait. AB - Foot placement is known to affect balance during gait; however, how foot placements are chosen is unknown. Objectives of this research were to analyze swing trajectories of the foot during gait with respect to the pelvis, and to propose a model of foot placement control which provides a stable base of support. Effects of gait speed and vision on this model of foot placement were then examined. Foot trajectories were analyzed using spherical coordinates referenced to the pelvis, termed the pelvic spherical coordinates (PSCs). A model was developed based on this coordinate system which predicts foot placement in terms of position and velocity with respect to the pelvis. It is proposed that foot placements are chosen to minimize the sum of PSC coordinates of the stance and swing feet. Foot velocity at heel contact is proposed to minimize the sum of the PSC stance and swing angular velocities. Experimental data were collected to test this model during walking trials of different speeds, both with and without vision. Results showed that sums of stance and swing feet PSCs were very close to zero at heel contact, supporting the positional control hypothesis. Sums of PSC velocities, however, were not zero at heel contact. Rather, individual swing leg PSC velocities were zero at heel contact, suggesting independent swing leg velocity control. Vision did not have an effect on position or velocity variables at heel contact. Gait speed did have an effect, particularly on PSC velocities at heel contact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798285 TI - An asymptotic solution for the contact of two biphasic cartilage layers. AB - This study addresses the hypothesis that interstitial fluid plays a major role in the load support mechanism of articular cartilage. An asymptotic solution is presented for two contacting biphasic cartilage layers under compression. This solution is valid for identical thin (i.e. epsilon = h'/a'0 << 1), frictionless cartilage layers, and for the 'early' time response (i.e. t' << (h')2/HAk) after the application of a step load. An equilibrium asymptotic solution is also presented (i.e.t'-->infinity). Here h' is the thickness, a'0 is a characteristic contact radius, HA is the aggregate modulus and k is the permeability of the cartilage layer. A main conclusion from this analysis is that the fluid phase of cartilage plays a major role in providing load support during the first 100-200 s after contact loading. Further, the largest component of stress in cartilage is the hydrostatic pressure developed in the interstitial fluid. For tissue fluid volume fraction (porosity) in the range 0.6 < or = phi f < or = 0.8, k = O(10( 15) m4/Ns) and HA = O(1 MPa), the peak magnitude of the principal effective (or elastic) stress may be as low as 14% of the peak hydrostatic pressure within the tissue, or the contact stress at the surface. In effect, the interstitial fluid shields the solid matrix from high normal stresses and strains. The asymptotic solution also shows that pressure-sensitive film measurements of intra-articular contact stress do not measure the elastic stress at the surface, but they rather provide a measure of the interstitial fluid pressure. Finally, this analysis provides strong support for the hypothesis that, if sudden loading causes shear failure within the cartilage-bone layer structure, this failure would take place at the cartilage-bone interface, and the plane of failure would be either parallel or perpendicular to this interface. PMID- 7798286 TI - Skeletal muscle stiffness in static and dynamic contractions. AB - Series elastic stiffness of rat gastrocnemius medialis muscle was determined by means of sinusoidal movements (180 Hz, 0.25% of muscle length) for various contraction conditions. The effects of muscle length, activation level, velocity, prestretch, and temperature on the force-stiffness relationship were investigated. All force-stiffness curves were transformed to a linear force-alpha curve (Ettema and Huijing, 1993; Morgan, 1977) to distinguish mathematically two series elastic components; a force dependent and force independent compliance. For all isometric conditions a typical force-stiffness curve was found, where stiffness increased with force, and this increase levelled off at higher forces. Stiffness in dynamic shortening and lengthening contractions is related to force in a completely different way than in isometric condition. An increase in temperature caused a decrease in muscle stiffness for a given force, and the effects of muscle length, activation level, and prestretch were small. It was concluded that the series elastic component of skeletal-muscle-tendon complex is probably located in more than two morphologically identifiable elements. Furthermore, we concluded that using a single series elastic element in muscle modelling is not appropriate to describe muscle behaviour under all conditions that occur during in vivo activation. PMID- 7798287 TI - A squeeze flow phenomenon at the closing of a bileaflet mechanical heart valve prosthesis. AB - In vivo cavitation in cardiovascular flow fields may occur under very unusual circumstances as a localized transient phenomenon which are confined to very small regions in the vicinity of the valve body or leaflet surface. The violent collapse of cavitation bubbles induces local erosion that may lead to structural damage. The fluid mechanical factors that may cause in vivo cavitation inception in mechanical heart valve (MHV) prostheses are investigated. It is established that the closing velocity of the leaflet holds the key to MHV cavitation. During the final phase of valve closing, the fluid mass in the gap space between the closing occluder and the valve's body is squeezed into motion by the rapidly approaching boundaries. The flow pattern created by this motion (termed 'squeeze flow'), is found to be related to the valve geometry, and the impact velocity of the closing leaflet. Given the closing velocity of the leaflet and the geometry of the MHV, computational flow dynamics (CFD) are made to determine the velocity distributions in the gap flow field of a bileaflet MHV in the mitral position. A two dimensional, time dependent model of the gap space show that flow velocity in the gap space can reach values as high as 30 ms-1 in regions near the edge of the inflow surface of the Edwards Duromedics (ED) MHV leaflet. This high speed stream ejected from the gap channel can create the conditions that characterize cavitation. The location of the isolated high speed region corresponds to the surface erosion that was observed in a number of damaged ED-MHV explants. PMID- 7798288 TI - Modeling of the wave transmission properties of large arteries using nonlinear elastic tubes. AB - We propose a new, simple way of constructing elastic tubes which can be used to model the nonlinear elastic properties of large arteries. The tube models are constructed from a silicon elastomer (Sylgard 184, Dow Corning), which exhibits a nonlinear behavior with increased stiffness at high strains. Tests conducted on different tube models showed that, with the proper choice of geometric parameters, the elastic properties, in terms of area-pressure relation and compliance, can be similar to that of real arteries. PMID- 7798289 TI - A method for the fatigue testing of pedicle screw fixation devices. AB - Spinal devices/instrumentation are used to augment the stability of a decompressed spinal segment during surgery. Like any other mechanical component, the device can fail. A standard in vitro test protocol, was developed to determine load vs number of cycles to failure curve for a pedicle screw-plate/rod type spinal device. The protocol based on the use of an 'artificial spine' model, is clinically relevant. The protocol was used to characterize the load-carrying capacities and failure modes of a specific pedicle screw-rod type fixation device to demonstrate its appropriateness. The devices (Kaneda) were tested in the quasi static as well as fatigue bending modes. In the bending fatigue mode, the devices failed at loads significantly smaller than the corresponding quasi-static failure load magnitude (806 N). The device exhibited an endurance limit in the fatigue bending mode. The device is not likely to exhibit failure if subjected to cyclic loads which cause less than 380 N axial compression (and an accompanying bending moment relative to the device of less than 13.57 Nm). The failures observed in specimens subjected to the fatigue tests ranged from complete to partial breakage of the paraspinal rods as opposed to failure due to permanent deformation (yielding) of the rods in the quasi-static bending test specimens. The protocol developed can be used for any other screw-plate/rod type spinal instrumentation. The use of a standard protocol by researchers would enable a comparison of various devices currently available in the market. Such comparative data would be useful for the scientific community, and agencies such as the FDA and ASTM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798290 TI - A physiological approach to the simulation of bone remodeling as a self organizational control process. AB - Although the capacity of bone to adapt to functional mechanical requirements has been known for more than a century, it is still unclear how the bone adaptation processes are regulated. We hypothesize that osteocytes are sensitive to mechanical loading and control the regulation of bone mass in their environment. Recently, simulation models of such a process were developed, using the finite element method. It was discovered that these models produce discontinuous structures, not unlike trabecular bone. However, it was also found that severe discontinuities violate the continuum assumption underlying the finite element method and that the solutions were element mesh dependent. We have developed a simulation model (which is physiologically and mechanically more consistent) which maintains the self-organizational characteristics but does not produce these discontinuities. This was accomplished by separating the sensor density and range of action from the mesh. The results clearly show that predicted trabecular morphology, i.e. sizes and branching of struts, depend on the actual relationship between local load, sensor density and range of influence. We believe that the model is suitable to study the relationship between trabecular morphology and load and can also explain adaptation of morphology, in the sense of 'Wolff's law'. PMID- 7798291 TI - Revisiting the debate: the use of new agents in previously untreated patients with small cell lung cancer; quality versus duration of survival. PMID- 7798293 TI - Antiproliferative effects of interferon gamma in combination with alpha difluoromethylornithine on human carcinoma cell cultures. AB - The antiproliferative effects of human recombinant interferon gamma (IFN gamma) in combination with alpha-difluoromethylornithine (DFMO) or as single agents were assessed on human cell cultures derived from carcinomas of the breast (MCF-7), the ovary (EFO-27) or the kidneys (EGI-4). Results were obtained in proliferation assays by direct cell counting. The cell lines differed considerably in their sensitivities to the antiproliferative effect of IFN gamma as compared by the 50% inhibition doses of the growth (ID50). In contrast to the findings with IFN gamma, similar antiproliferative effects resulted from the application of comparable doses of DFMO. While IFN gamma induced cytotoxic effects in EGI-4 cells, DFMO produced only cytostatic actions in the cell lines analyzed. Synergistic growth inhibition resulted from the combined application of IFN gamma and DFMO in EFO-27 cell cultures. This finding was most pronounced after treatment with IFN gamma or DFMO doses below the respective ID50 values. However, antagonistic effects occurred in cells of the line EGI-4 after DFMO had been combined with IFN gamma at concentrations below the cytotoxic dose range. Within the sensitivity of our proliferation assay, no synergistic interactions were found in MCF-7 cell cultures. In the cell lines tested, no relation between the sensitivity for the single agents and the effectivity of the drug combination was identified. Despite promising synergistic effects in the moderately IFN gamma sensitive ovarian carcinoma cell line EFO-27, the efficacy of the IFN gamma/DFMO combination was restrained by possible antagonistic effects as demonstrated in the highly IFN gamma-sensitive EGI-4 renal carcinoma cell cultures. We conclude that the differential interaction patterns in the cell cultures analyzed preclude general suggestions for clinical studies using IFN gamma and DFMO. PMID- 7798292 TI - Growth inhibition of human gastrointestinal cancer cells by cyclosporin A. AB - We have studied the ability of cyclosporin A (CsA) to inhibit the growth of human AGS gastric and HT29 colon carcinoma cells in vitro. Using continuous drug exposure in growth assays of cultured tumour cells we found that CsA produced a dose-dependent growth inhibition in gastric and colon cancer cells with a half maximal effect at 5 microM and 6 microM CsA respectively. The growth inhibition of CsA was reversible in AGS cells, when the tumour cells were incubated in normal growth medium following CsA treatment. Trypan blue dye exclusion in AGS cells indicated a cytostatic rather than a cytotoxic effect in the concentration range used. Coincubation of CsA-treated cells with 10-400 U/ml interleukin-2 (IL 2) could not abrogate this growth inhibition, suggesting an IL-2 independent mechanism of action. Flow-cytometric analysis did not reveal a phase arrest of the gastric cancer cells within the cell cycle. We conclude from our experiments that CsA cytostatically and reversibly inhibits the growth of human gastric cancer cells in a dose-dependent manner. In contrast to its mechanism of action in lymphocytes, this direct antiproliferative effect of CsA seems not to be mediated by an IL-2-dependent pathway or a cell-cycle-phase arrest of the tumour cells. PMID- 7798294 TI - A new cytogenetic subgroup in lipomas: loss of chromosome 16 material in spindle cell and pleomorphic lipomas. AB - Six spindle cell lipomas and two pleomorphic lipomas were analyzed cytogenetically. One spindle cell lipoma had a supernumerary ring chromosome as the sole anomaly. The other five spindle cell lipomas and both pleomorphic lipomas had hypodiploid stemlines with monosomy 16 or unbalanced aberrations leading to loss of 16q13-qter, a feature distinguishing these lipoma subtypes from other benign and borderline adipose tissue tumor histotypes. unbalanced aberrations of chromosomes 13 and 10 were found in five and three cases respectively; 13q12 was lost in all of these cases, whereas there was no common deleted segment in chromosome 10. No aberrations involving 12q13-15, which are frequent in typical lipomas, were found. Both pleomorphic lipomas, but none of the spindle cell lipomas, had hypotetraploid sidelines, multiple nonclonal aberrations, and telomeric associations. The present findings reveal a new cytogenetic/histopathological association in adipose tissue tumors. PMID- 7798295 TI - Sublethal damage repair after fractionated irradiation in endometrial cancer cell lines tested with the 96-well plate clonogenic assay. AB - Two long-established and seven newly established endometrial adenocarcinoma cell lines were tested for their capacity to repair sublethal damage after fractionated irradiation. Cell survival was determined with the 96-well plate clonogenic assay based on limiting dilutions. Total radiation doses of 0.75 Gy, 1.25 Gy, 2.50 Gy, 5.00 Gy and 7.50 Gy were used either as a single dose or divided into two or three equal fractions with a 24 h interval. Survival data were fitted to the linear quadratic model, and the area under the survival curve (AUC), equivalent to the mean inactivation dose, was obtained with numerical integration. The amount of sublethal damage repair (SLDR) was expressed as an area-under-the-curve (AUC) ratio comparing survivals from fractionated-dose with those from single-dose experiments. SLDR capacity of the cell lines expressed as an AUC ratio varied between 1.00 and 1.59, and the mean was 1.17. Two highly radiosensitive cell lines were found to be SLDR-deficient, but most of the cell lines studied had some SLDR capacity. We have earlier shown that endometrial cancer cell lines as a group are more radiosensitive than squamous-cell carcinoma (SCC) lines. Data obtained in this study suggest that the capacity for SLDR in these cell lines is rather limited compared with the majority of SCC lines tested. This finding underlines further the high radioresponsiveness of endometrial cancer. PMID- 7798296 TI - Effects of differentiation-inducing agents on purine nucleotide metabolism in an ovarian cancer cell line. AB - The effects of the differentiation-inducing agents sodium butyrate (NaOBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine nucleotide metabolism, was studied in an ovarian carcinoma cell line (GZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and DMSO moderately decelerated purine synthesis de novo, but MA accelerated it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. NaOBt and DMSO did not affect the cellular nucleotide content, but MA caused a 73% decrease in GTP content and about a 50% increase in the cellular content of UTP. The following alterations in cellular enzyme activity were observed 72 h following exposure: NaOBt decreased the activity of hypoxanthine-guanine phosphoribosyltransferase and increased the activity of IMP and of AMP 5'-nucleotidases, DMSO increased the activity of IMP 5'-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line studied, the differentiation process induced by NaOBt and DMSO may be associated with a general shift in the direction of purine metabolism from anabolism to catabolism, whereas that induced by MA is associated with a specific decrease in the production of GTP. PMID- 7798297 TI - Argyrophilic nucleolar organizer regions in the evaluation of tumour progression in the oral mucosa: correlation with tissue pathology. AB - The present study has analysed the numbers of argyrophilic nucleolar organizer regions (AgNOR) in normal tissues and in premalignant and malignant lesions of the oral mucosa in order to assess their potential as a biological marker for tumour progression. On comparison of AgNOR numbers in different lesions, carcinomas showed the highest number (4.65 +/- 0.98) compared to leukoplakias (2.38 +/- 0.47) and normal tissues (1.53 +/- 0.39). Spindle cell carcinomas and poorly differentiated squamous cell carcinomas had higher AgNOR counts than well differentiated carcinomas. In various clinically different types of oral leukoplakia, the lowest AgNOR counts were observed in homogenous leukoplakia and the highest in speckled leukoplakia. No significant difference in AgNOR number was observed between non-dysplastic and dysplastic leukoplakia, although a significant difference was evident between dysplastic leukoplakia and normal oral mucosa. Correlating the AgNOR count and tumour progression, a significantly high positive correlation coefficient (r = 0.7969, P = 0.0000) was observed. PMID- 7798298 TI - Aberrations of the APC gene in primary breast carcinoma. AB - Aberrations of the APC gene, which plays an important role in the genesis of familial adenomatous polyposis and colorectal carcinoma, were investigated in 31 surgical specimens of primary breast carcinoma. These studies utilized the polymerase chain reaction followed by restriction-fragment-length polymorphism and single-strand-conformation polymorphism analyses combined with tumor cell enrichment by cell sorting. Loss of heterozygosity at the APC locus was detected in 8 (38%) of 21 informative cases, but only 2 (6%) of 31 tumors carried a mutated APC gene. Direct DNA sequencing analysis confirmed mutations at codon 1081 (AGC to ATC) resulting in an amino acid substitution of serine for isoleucine, and at codon 1096 (CAG to CAT) resulting in a substitution of glutamine for histidine. There were no significant correlations between the loss of heterozygosity or mutation at the APC locus and any clinicopathological characteristics. Our present observations suggest that the mutations of the APC gene may play an important role in the genesis of certain breast carcinomas, and that another tumor-suppressor gene, which is the true target of frequent loss of heterozygosity, may exist near the APC gene. PMID- 7798301 TI - 85th annual meeting of the American Association for Cancer Research. San Francisco, California, April 1994. PMID- 7798299 TI - Occasional loss of constitutive heterozygosity at 11p15.5 and imprinting relaxation of the IGFII maternal allele in hepatoblastoma. AB - The 11p15.5 chromosomal region contains one or more loci involved in congenital developmental abnormalities and in the genesis of embryonal tumors, such as Wilms' tumor, embryonal rhabdomyosarcoma, and hepatoblastoma. In these tumors, a loss of constitutive heterozygosity, selectively involving a specific parental allele, suggests both the presence of onco-suppressor genes and a phenomenon of genomic imprinting. We present evidence that both genetic events could be occasionally involved in hepatoblastoma. In fact, loss of heterozygosity at 11p15.5 could be documented in 3 of 13 patients with hepatoblastoma, and in 2 cases the paternal origin of the residual allele in the tumor was assessed. Moreover, imprinting of the paternal IGFII allele and the maternal H19 allele was confirmed in normal tissues of 5 informative patients. Finally, imprinting relaxation of IGFII was detected in the tumor tissue of 1 patient. PMID- 7798302 TI - 30th annual meeting of the American Society of Clinical Oncology. Dallas, Texas, May 1994. PMID- 7798300 TI - Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients. AB - Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.0% of the cases HER-2/neu was overexpressed, and in 46.7% the p53 protein level was increased. Expression of these two oncogene products was closely correlated. Overexpression of both oncogenes was associated with larger tumour size and negative hormone receptor. The percentage of HER-2/neu and p53 overexpression was higher in node-positive patients, although statistical evaluation was not significant. While overexpression of HER 2/neu as well as p53 in node-positive patients was associated insignificantly with shorter disease-free survival, a significant difference could be documented when the disease-free survival of patients with overexpression of both oncogene proteins was compared to that of patients with no overexpression. PMID- 7798303 TI - Gastric and esophageal cancers: perspectives from a U.S.-Japan meeting. Hawaii, February 6-7, 1993. PMID- 7798304 TI - Preliminary results of a phase I/II trial of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer. AB - Paclitaxel represents a novel antitumour agent with demonstrated activity in cisplatin-sensitive tumours, particularly ovarian cancer. In addition, responses to paclitaxel have been observed in patients with cisplatin-refractory ovarian cancer. The role of paclitaxel in the treatment of testicular cancer has not been explored so far. Despite the generally high cure rates in patients with metastatic testicular cancer, patients with relapsed disease not responding to platin-based salvage chemotherapy have an extremely poor prognosis. In a phase I/II trial 10 patients with relapsed, cisplatin-refractory malignant germ-cell tumours were treated with paclitaxel as 6-h infusions (8 patients) or 3-h infusions (2 patients) at doses from 135 mg/m2 to 310 mg/m2 at 3-week intervals. Three patients achieved a response to paclitaxel, but disease recurred shortly in two patients after two and four cycles of therapy, respectively. One patient has remained in marker-negative partial response for more than 5 months. The toxicity of paclitaxel was tolerable for a dose range from 135 mg/m2 to 225 mg/m2. Granulocytopenia, WHO grades 3 and 4, occurred in all patients but was of short duration (median 3 days; range: 2-7 days). Other toxicities such as mucositis (5 patients grade 1), neurotoxicity (1 patient grade 1, 2 patients grade 2), infection (1 patient grade 3) and diarrhoea (1 patient grade 2) were not dose limiting. There were no hypersensitivity reactions, but 1 patient developed severe myalgias during therapy with paclitaxel. Six patients with documented cisplatin-refractory disease were retreated with cisplatin-based chemotherapy after paclitaxel treatment and, in 4 of these, tumour responses of 3, 4, 5 and more than 5 months duration were achieved. In order to explore the role of paclitaxel in relapsed and/or cisplatin-refractory testicular cancer a phase II study using a 3-h infusion of 225 mg/m2 paclitaxel every 3 weeks, conducted by the German Testicular Cancer Study Group, is ongoing. PMID- 7798305 TI - An end in sight: tropomodulin. PMID- 7798306 TI - The Alzheimer's disease sphinx: a riddle with plaques and tangles. PMID- 7798307 TI - NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. AB - We report the identification and molecular characterization of a novel nucleolar protein of rat liver. As shown by coimmunoprecipitation this protein is associated with a previously identified nucleolar protein, Nopp140, in an apparently stoichiometric complex and has therefore been termed NAP57 (Nopp140 associated protein of 57 kD). Immunofluorescence and immunogold electron microscopy with NAP57 specific antibodies show colocalization with Nopp140 to the dense fibrillar component of the nucleolus, to coiled bodies, and to the nucleoplasm. Immunogold staining in the nucleoplasm is occasionally seen in the form of curvilinear tracks between the nucleolus and the nuclear envelope, similar to those previously reported for Nopp140. These data suggest that Nopp140 and NAP57 are indeed associated with each other in these nuclear structures. The cDNA deduced primary structure of NAP57 shows a protein of a calculated molecular mass of 52,070 that contains a putative nuclear localization signal near its amino and carboxy terminus and a hydrophobic amino acid repeat motif extending across 84 residues. Like Nopp140, NAP57 lacks any of the known consensus sequences for RNA binding which are characteristic for many nucleolar proteins. Data bank searches revealed that NAP57 is a highly conserved protein. A putative yeast (S. cerevisiae) homolog is 71% identical. Most strikingly, there also appears to be a smaller prokaryotic (E. coli and B. subtilis) homolog that is nearly 50% identical to NAP57. This indicates that NAP57 and its putative homologs might serve a highly conserved function in both pro- and eukaryotes such as chaperoning of ribosomal proteins and/or of preribosome assembly. PMID- 7798308 TI - Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex. AB - From a panel of monoclonal antibodies raised against fractions of rat liver nuclear envelopes (NEs), we have identified an antibody, RL30, which reacts with novel nuclear pore complex (NPC) antigens that are not O-glycosylated. By immunofluorescence staining of cultured cells, RL30 reacts exclusively with the NE in a punctate pattern that largely coincides with that of identified NPC proteins. RL30 labels only the cytoplasmic surface of the NPC in immunogold electron microscopy, predominantly in peripheral regions nearby the cytoplasmic ring. In immunoblots of isolated rat liver NEs and cultured rat cells, RL30 recognizes a 265-kD band, as well as a series of 175-265-kD bands in rat liver NEs that are likely to be proteolytic products of p265. Sequencing of peptides from the 175- and 265-kD RL30 antigens of rat liver revealed that they are both closely related to human Tpr, a protein whose amino-terminal 150-250 amino acids appear in oncogenic fusions with the kinase domains of the met, trk, and raf protooncogenes. We found that in vitro translation of human Tpr mRNA yields a major 265-kD band. Considered together, these data indicate that the 265-kD RL30 antigen in the NPC is the rat homologue of Tpr. Interestingly, Tpr contains an exceptionally long predicted coiled coil domain (approximately 1600 amino acids). The localization and predicted structure of Tpr suggest that it is a component of the cytoplasmic fibrils of the NPC implicated in nuclear protein import. Immunofluorescence microscopy shows that during NPC reassembly at the end of mitosis, Tpr becomes concentrated at the NE significantly later than O-linked glycoproteins, including p62. This indicates that reassembly of the NPC after mitosis is a stepwise process, and that the Tpr-containing peripheral structures are assembled later than p62. PMID- 7798310 TI - Translation of the psbA mRNA of Chlamydomonas reinhardtii requires a structured RNA element contained within the 5' untranslated region. AB - Translational regulation is a key modulator of gene expression in chloroplasts of higher plants and algae. Genetic analysis has shown that translation of chloroplast mRNAs requires nuclear-encoded factors that interact with chloroplastic mRNAs in a message-specific manner. Using site-specific mutations of the chloroplastic psbA mRNA, we show that RNA elements contained within the 5' untranslated region of the mRNA are required for translation. One of these elements is a Shine-Dalgarno consensus sequence, which is necessary for ribosome association and psbA translation. A second element required for high levels of psbA translation is located adjacent to and upstream of the Shine-Dalgarno sequence, and maps to the location on the RNA previously identified as the site of message-specific protein binding. This second element appears to act as a translational attenuator that must be overcome to activate translation. Mutations that affect the secondary structure of these RNA elements greatly reduce the level of psbA translation, suggesting that secondary structure of these RNA elements plays a role in psbA translation. These data suggest a mechanism for translational activation of the chloroplast psbA mRNA in which an RNA element containing the ribosome-binding site is bound by message-specific RNA binding proteins allowing for increased ribosome association and translation initiation. These elements may be involved in the light-regulated translation of the psbA mRNA. PMID- 7798309 TI - Facilitated nuclear transport of calmodulin in tissue culture cells. AB - Calmodulin (CaM) potentiates Ca(2+)-dependent signaling pathways in both the cytoplasm and nucleus. We have investigated the mechanism of CaM nuclear transport using tissue culture cell microinjection and a permeabilized cell import assay. The inhibition of CaM import by the translocation inhibitor wheat germ agglutinin (WGA) and by chilling, indicates that CaM import is facilitated, but because ATP depletion does not affect CaM import, the mechanism does not appear to be active. Chilling and WGA arrest persist in ATP-depleted cells, indicating that CaM is not retained in the cytoplasm by an ATP-dependent mechanism. In permeabilized cells, both Ca(2+)-CaM and Ca(2+)-free CaM are sensitive to extract-dependent WGA and chilling import inhibition. Titration experiments in microinjected and permeabilized cells indicate that a saturable cytosolic factor(s) mediates chilling and WGA arrest. PMID- 7798311 TI - Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44. AB - The import of preproteins into mitochondria involves translocation of the polypeptide chains through putative channels in the outer and inner membranes. Preprotein-binding proteins are needed to drive the unidirectional translocation of the precursor polypeptides. Two of these preprotein-binding proteins are the peripheral inner membrane protein MIM44 and the matrix heat shock protein hsp70. We report here that MIM44 is mainly exposed on the matrix side, and a fraction of mt-hsp70 is reversibly bound to the inner membrane. Mt-hsp70 binds to MIM44 in a 1:1 ratio, suggesting that mt-hsp70 is localizing to the membrane via its interaction with MIM44. Formation of the complex requires a functional ATPase domain of mt-hsp70. Addition of Mg-ATP leads to dissociation of the complex. Overexpression of mt-hsp70 rescues the protein import defect of mutants in MIM44; conversely, overexpression of MIM44 rescues protein import defects of mt-hsp70 mutants. In addition, yeast strains with conditional mutations in both MIM44 and mt-hsp70 are barely viable, showing a synthetic growth defect compared to strains carrying single mutations. We propose that MIM44 and mt-hsp70 cooperate in translocation of preproteins. By binding to MIM44, mt-hsp70 is recruited at the protein import sites of the inner membrane, and preproteins arriving at MIM44 may be directly handed over to mt-hsp70. PMID- 7798313 TI - The small GTP-binding protein rab6 functions in intra-Golgi transport. AB - Rab6 is a ubiquitous ras-like GTP-binding protein associated with the membranes of the Golgi complex (Goud, B., A. Zahraoui, A. Tavitian, and J. Saraste. 1990. Nature (Lond.). 345:553-556; Antony, C., C. Cibert, G. Geraud, A. Santa Maria, B. Maro, V. Mayau, and B. Goud. 1992. J. Cell Sci. 103: 785-796). We have transiently overexpressed in mouse L cells and human HeLa cells wild-type rab6, GTP (rab6 Q72L), and GDP (rab6 T27N) -bound mutants of rab6 and analyzed the intracellular transport of a soluble secreted form of alkaline phosphatase (SEAP) and of a plasma membrane protein, the hemagglutinin protein (HA) of influenza virus. Over-expression of wild-type rab6 and rab6 Q72L greatly reduced transport of both markers between cis/medial (alpha-mannosidase II positive) and late (sialyl-transferase positive) Golgi compartments, without affecting transport from the endoplasmic reticulum (ER) to cis/medial-Golgi or from the trans-Golgi network (TGN) to the plasma membrane. Whereas overexpression of rab6 T27N did not affect the individual steps of transport between ER and the plasma membrane, it caused an apparent delay in secretion, most likely due to the accumulation of the transport markers in late Golgi compartments. Overexpression of both rab6 Q72L and rab6 T27N altered the morphology of the Golgi apparatus as well as that of the TGN, as assessed at the immunofluorescence level with several markers. We interpret these results as indicating that rab6 controls intra-Golgi transport, either acting as an inhibitor in anterograde transport or as a positive regulator of retrograde transport. PMID- 7798312 TI - Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells. AB - The carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), or a closely-related sequence, is important for ER localization of both lumenal as well as type II membrane proteins. This sequence functions as a retrieval signal at post-ER compartment(s), but the exact compartment(s) where the retrieval occurs remains unresolved. With an affinity-purified antibody against the carboxyl-terminal sequence of the mammalian KDEL receptor, we have investigated its subcellular localization using immunogold labeling on thawed cryosections of different tissues, such as mouse spermatids and rat pancreas, as well as HeLa, Vero, NRK, and mouse L cells. We show that rab1 is an excellent marker of the intermediate compartment, and we use this marker, as well as budding profiles of the mouse hepatitis virus (MHV) in cells infected with this virus, to identify this compartment. Our results demonstrate that the KDEL receptor is concentrated in the intermediate compartment, as well as in the Golgi stack. Lower but significant labeling was detected in the rough ER. In general, only small amounts of the receptor were detected on the trans side of the Golgi stack, including the trans-Golgi network (TGN) of normal cells and tissues. However, some stress conditions, such as infection with vaccinia virus or vesicular stomatitis virus, as well as 20 degrees C or 43 degrees C treatment, resulted in a significant shift of the distribution towards the trans-TGN side of the Golgi stack. This shift could be quantified in HeLa cells stably expressing a TGN marker. No significant labeling was detected in structures distal to the TGN under all conditions tested. After GTP gamma S treatment of permeabilized cells, the receptor was detected in the beta-COP-containing buds/vesicles that accumulate after this treatment, suggesting that these vesicles may transport the receptor between compartments. We propose that retrieval of KDEL-containing proteins occurs at multiple post-ER compartments up to the TGN along the exocytotic pathway, and that within this pathway, the amounts of the receptor in different compartments varies according to physiological conditions. PMID- 7798314 TI - Sorting of synaptophysin into special vesicles in nonneuroendocrine epithelial cells. AB - Synaptophysin is a major transmembrane glycoprotein of a type of small vesicle with an electron-translucent content (SET vesicles), including the approximately 50-nm presynaptic vesicles in neuronal cells, and of similar, somewhat larger (< or = approximately 90 nm) vesicles (SLMV) in neuroendocrine (NE) cells. When certain epithelial non-NE cells, such as human hepatocellular carcinoma PLC cells, were cDNA transfected to synthesize synaptophysin, the new molecules appeared in specific SET vesicles. As this was in contrast to other reports that only NE cells were able to sort synaptophysin away from other plasma membrane proteins into presynaptic- or SLMV-type vesicles, we have further characterized the vesicles containing synaptophysin in transfected PLC cells. Using fractionation and immunoisolation techniques, we have separated different kinds of vesicles, and we have identified a distinct type of synaptophysin-rich, small (30-90-nm) vesicle that contains little, if any, protein of the constitutive secretory pathway marker hepatitis B surface antigen, of the fluid phase endocytosis marker HRP, and of the plasma membrane recycling endosomal marker transferrin receptor. In addition, we have found variously sized vesicles that contained both synaptophysin and transferrin receptor. A corresponding result was also obtained by direct visualization, using double-label immunofluorescence microscopy for the endocytotic markers and synaptophysin in confocal laser scan microscopy and in double-immunogold label electron microscopy. We conclude that diverse non-NE cells of epithelial nature are able to enrich the "foreign" molecule synaptophysin in a category of SET vesicles that are morphologically indistinguishable from SLMV of NE cells, including one type of vesicle in which synaptophysin is sorted away from endosomal marker proteins. Possible mechanisms of this sorting are discussed. PMID- 7798316 TI - Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. AB - Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids. Immunofluorescence and laser scan microscopy revealed that chick full-length occludin introduced into human and bovine epithelial cells was correctly delivered to and incorporated into preexisting TJ. Further transfection studies with various deletion mutants showed that the domain E, especially its COOH-terminal approximately 150 amino acids (domain E358/504), was necessary for the localization of occludin at TJ. Secondly, domain E was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase, and this fusion protein was shown to be specifically bound to a complex of ZO-1 (220 kD) and ZO-2 (160 kD) among various membrane peripheral proteins. In vitro binding analyses using glutathione-S-transferase fusion proteins of various deletion mutants of domain E narrowed down the sequence necessary for the ZO-1/ZO 2 association into the domain E358/504. Furthermore, this region directly associated with the recombinant ZO-1 produced in E. coli. We concluded that occludin itself can localize at TJ and directly associate with ZO-1. The coincidence of the sequence necessary for the ZO-1 association with that for the TJ localization suggests that the association with underlying cytoskeletons through ZO-1 is required for occludin to be localized at TJ. PMID- 7798315 TI - The polymeric immunoglobulin receptor accumulates in specialized endosomes but not synaptic vesicles within the neurites of transfected neuroendocrine PC12 cells. AB - We have expressed in neuroendocrine PC12 cells the polymeric immunoglobulin receptor (pIgR), which is normally targeted from the basolateral to the apical surface of epithelial cells. In the presence of nerve growth factor, PC12 cells extend neurites which contain synaptic vesicle-like structures and regulated secretory granules. By immunofluorescence microscopy, pIgR, like the synaptic vesicle protein synaptophysin, accumulates in both the cell body and the neurites. On the other hand, the transferrin receptor, which normally recycles at the basolateral surface in epithelial cells, and the cation-independent mannose 6 phosphate receptor, a marker of late endosomes, are largely restricted to the cell body. pIgR internalizes ligand into endosomes within the cell body and the neurites, while uptake of ligand by the low density lipoprotein receptor occurs primarily into endosomes within the cell body. We conclude that transport of membrane proteins to PC12 neurites as well as to specialized endosomes within these processes is selective and appears to be governed by similar mechanisms that dictate sorting in epithelial cells. Additionally, two types of endosomes can be identified in polarized PC12 cells by the differential uptake of ligand, a housekeeping type in the cell bodies and a specialized endosome in the neurites. Recent findings suggest that specialized axonal endosomes in neurons are likely to give rise to synaptic vesicles (Mundigl, O., M. Matteoli, L. Daniell, A. Thomas-Reetz, A. Metcalf, R. Jahn, and P. De Camilli. 1993. J. Cell Biol. 122:1207-1221). Although pIgR reaches the specialized endosomes in the neurites of PC12 cells, we find by subcellular fractionation that under a variety of conditions it is efficiently excluded from synaptic vesicle-like structures as well as from secretory granules. PMID- 7798318 TI - How an actin network might cause fountain streaming and nuclear migration in the syncytial Drosophila embryo. AB - We show here using time-lapse video tapes that cytoplasmic streaming causes nuclear migration along the anterior-posterior axis (axial expansion) in the early syncytial embryo of Drosophila melanogaster. Using confocal microscopy and labeled phalloidin we explore the distribution of F-actin during axial expansion. We find that a network of F-actin fibers fills the cytoplasm in the embryo. This actin network partially disassembles around the nuclei during axial expansion. Our observations of normal development, fixed embryos, and drug injection experiments indicate that disassembly of the actin network generates cytoplasmic movements. We suggest that the cell cycle regulates disassembly of the actin network, and that this process may be mediated directly or indirectly by the microtubules. The cytoplasmic movements we observe during axial expansion are very similar to fountain streaming in the pseudopod of amoebae, and by analogy with the pseudopod we propose a working hypothesis for axial expansion based on solation-contraction coupling within the actin network. PMID- 7798317 TI - Tropomodulin caps the pointed ends of actin filaments. AB - Many proteins have been shown to cap the fast growing (barbed) ends of actin filaments, but none have been shown to block elongation and depolymerization at the slow growing (pointed) filament ends. Tropomodulin is a tropomyosin-binding protein originally isolated from red blood cells that has been localized by immunofluorescence staining to a site at or near the pointed ends of skeletal muscle thin filaments (Fowler, V. M., M. A., Sussman, P. G. Miller, B. E. Flucher, and M. P. Daniels. 1993. J. Cell Biol. 120: 411-420). Our experiments demonstrate that tropomodulin in conjunction with tropomyosin is a pointed end capping protein: it completely blocks both elongation and depolymerization at the pointed ends of tropomyosin-containing actin filaments in concentrations stoichiometric to the concentration of filament ends (Kd < or = 1 nM). In the absence of tropomyosin, tropomodulin acts as a "leaky" cap, partially inhibiting elongation and depolymerization at the pointed filament ends (Kd for inhibition of elongation = 0.1-0.4 microM). Thus, tropomodulin can bind directly to actin at the pointed filament end. Tropomodulin also doubles the critical concentration at the pointed ends of pure actin filaments without affecting either the rate of extent of polymerization at the barbed filament ends, indicating that tropomodulin does not sequester actin monomers. Our experiments provide direct biochemical evidence that tropomodulin binds to both the terminal tropomyosin and actin molecules at the pointed filament end, and is the long sought-after pointed end capping protein. We propose that tropomodulin plays a role in maintaining the narrow length distributions of the stable, tropomyosin-containing actin filaments in striated muscle and in red blood cells. PMID- 7798319 TI - Bypassing anaphase by fission yeast cut9 mutation: requirement of cut9+ to initiate anaphase. AB - A novel anaphase block phenotype was found in fission yeast temperature-sensitive cut9 mutants. Cells enter mitosis with chromosome condensation and short spindle formation, then block anaphase, but continue to progress into postanaphase events such as degradation of the spindle, reformation of the postanaphase cytoplasmic microtubule arrays, septation, and cytokinesis. The cut9 mutants are defective in the onset of anaphase and possibly in the restraint of postanaphase events until the completion of anaphase. The cut9+ gene encodes a 78-kD protein containing the 10 34-amino acid repeats, tetratricopeptide repeats (TPR), and similar to budding yeast Cdc16. It is essential for viability, and the mutation sites reside in the TPR. The three genes, namely, nuc2+, scn1+, and scn2+, genetically interact with cut9+. The nuc2+ and cut9+ genes share an essential function to initiate anaphase. The cold-sensitive scn1 and scn2 mutations, defective in late anaphase, can suppress the ts phenotype of cut9. PMID- 7798320 TI - Regulation of Chlamydomonas flagellar dynein by an axonemal protein kinase. AB - Genetic, biochemical, and structural data support a model in which axonemal radial spokes regulate dynein-driven microtubule sliding in Chlamydomonas flagella. However, the molecular mechanism by which dynein activity is regulated is unknown. We describe results from three different in vitro approaches to test the hypothesis that an axonemal protein kinase inhibits dynein in spoke-deficient axonemes from Chlamydomonas flagella. First, the velocity of dynein-driven microtubule sliding in spoke-deficient mutants (pf14, pf17) was increased to wild type level after treatment with the kinase inhibitors HA-1004 or H-7 or by the specific peptide inhibitors of cAMP-dependent protein kinase (cAPK) PKI(6 22)amide or N alpha-acetyl-PKI(6-22)amide. In particular, the peptide inhibitors of cAPK were very potent, stimulating half-maximal velocity at 12-15 nM. In contrast, kinase inhibitors did not affect microtubule sliding in axonemes from wild-type cells. PKI treatment of axonemes from a double mutant missing both the radial spokes and the outer row of dynein arms (pf14pf28) also increased microtubule sliding to control (pf28) velocity. Second, addition of the type-II regulatory subunit of cAPK (RII) to spoke-deficient axonemes increased microtubule sliding to wild-type velocity. Addition of 10 microM cAMP to spokeless axonemes, reconstituted with RII, reversed the effect of RII. Third, our previous studies revealed that inner dynein arms from the Chlamydomonas mutants pf28 or pf14pf28 could be extracted in high salt buffer and subsequently reconstituted onto extracted axonemes restoring original microtubule sliding activity. Inner arm dyneins isolated from PKI-treated axonemes (mutant strain pf14pf28) generated fast microtubule sliding velocities when reconstituted onto both PKI-treated or control axonemes. In contrast, dynein from control axonemes generated slow microtubule sliding velocities on either PKI-treated or control axonemes. Together, the data indicate that an endogenous axonemal cAPK-type protein kinase inhibits dynein-driven microtubule sliding in spoke-deficient axonemes. The kinase is likely to reside in close association with its substrate(s), and the substrate targets are not exclusively localized to the central pair, radial spokes, dynein regulatory complex, or outer dynein arms. The results are consistent with a model in which the radial spokes regulate dynein activity through suppression of a cAMP-mediated mechanism. PMID- 7798321 TI - Long-range signaling in growing neurons after local elevation of cyclic AMP dependent activity. AB - Cyclic AMP-dependent activity at the growth cone or the soma of cultured Xenopus spinal neurons was elevated by local extracellular perfusion of the neuron with culture medium containing 8-bromoadenosine 3',5'-cyclic monophosphate (8-br-cAMP) or forskolin. During local perfusion of one of the growth cones of multipolar neurons with these drugs, the perfused growth cone showed further extension, while the distant, unperfused growth cones were inhibited in their growth. Local perfusion of the growth cone with culture medium or local perfusion with 8-br cAMP at a cell-free region 100 microns away from the growth cone did not produce any effect on the extension of the growth cone. Reduced extension of all growth cones was observed when the perfusion with 8-br-cAMP was restricted to the soma. The distant inhibitory effect does not depend on the growth of the perfused growth cone since local coperfusion of the growth cone with 8-br-cAMP and colchicine inhibited growth on both perfused and unperfused growth cones, while local perfusion with colchicine alone inhibited only the perfused growth cone. The distant inhibitory effect was abolished when the perfusion of 8-br-cAMP was carried out together with kinase inhibitor H-8, suggesting the involvement of cAMP-dependent protein kinase and/or its downstream factors in the long-range inhibitory signaling. Uniform exposure of the entire neuron to bath-applied 8-br cAMP, however, led to enhanced growth activity at all growth cones. Thus, local elevation of cAMP-dependent activity produces long-range and opposite effects on distant parts of the neuron, and a cytosolic gradient of second messengers may produce effects distinctly different from those following uniform global elevation of the messenger, leading to differential growth regulation at different regions of the same neuron. PMID- 7798322 TI - Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis. AB - We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes," which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death. PMID- 7798323 TI - Recessive mutations in a common pathway block thymocyte apoptosis induced by multiple signals. AB - The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls genes necessary to initiate glucocorticoid-induced thymocyte apoptosis. We have performed a genetic analysis of thymocyte cell death by isolating and characterizing a panel of GR+ dexamethasone-resistant mutants of the murine WEHI7.2 thymocyte cell line. These apoptosis-defective (Apt-) mutants were used to identify previously unknown early steps in the apoptotic pathway. The Apt- mutants contain nonglucocorticoid receptor, recessive mutations in genes that represent multiple complementation groups. These mutations block apoptosis induced by dexamethasone, gamma irradiation, and c-AMP treatment before the point where Bcl-2 exerts its protective effect. We propose that different signals share a common apoptotic pathway, and that the induction of apoptosis involves multiple precommitment steps that can be blocked by recessive mutations. PMID- 7798325 TI - A potential role for tetranectin in mineralization during osteogenesis. AB - Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of approximately 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the cartilage of the shark, but the gene expression pattern in the mammalian skeletal system has not been determined. In the present study we have examined the expression pattern and putative function of tetranectin during osteogenesis. In the newborn mouse, strong tetranectin immunoreactivity was found in the newly formed woven bone around the cartilage anlage in the future bone marrow and along the periosteum forming the cortex. No tetranectin immunoreactivity was found in the proliferating and hypertrophic cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p < 0.01), supporting the notion that tetranectin may play an important direct and/or indirect role during osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro. PMID- 7798326 TI - A comparison of the early development of ischaemic damage following permanent middle cerebral artery occlusion in rats as assessed using magnetic resonance imaging and histology. AB - Recent developments in diffusion-weighted imaging (DWI) have enabled the pathological changes that occur during cerebral ischaemia to be studied. The present studies utilised DWI to investigate the development of early ischaemic changes following permanent middle cerebral artery (MCA) occlusion in the rat, which represents a model of stroke. An increased DWI signal was seen in the region of the occluded MCA and this was detectable as early as 1 h postocclusion. DWI images were obtained at nine stereotactic levels throughout the brain, providing a quantifiable measure of the volume of increased signal intensity in each animal. At 1 h post-MCA occlusion the hyperintense areas were seen in the frontoparietal cortex and lateral caudate nucleus; these areas represent the core of the infarct and no protection is seen with any compounds in these areas. There was a progressive increase in the area of hyperintensity up to 4 h post-MCA occlusion, and at this time point the hyper-intensity was seen in the dorsolateral cortex and caudate nucleus. At 4 h post-MCA occlusion there was a significant correlation between the volume of hemispheric and cortical ischaemic damage measured using DWI and histology. Thus, it appears that the increased DWI signal seen during the early time points after MCA occlusion was demarcating tissue that was destined for infarction. The area beyond the hyperintense region at 1 h represents the so-called "penumbral" region, because with increasing time (post-MCA occlusion) this area became incorporated into the infarct. There was also a slight increase in infarct size between 4 and 24 h, when assessed using DWI or histology, although two groups of animals were being compared, as opposed to the time-course study, in which just one group of animals was used. At 24 h post-MCA occlusion there was a good correlation between DWI, histology, and conventional T2 weighted imaging. There was no further increase in size of the infarct between 24 h and 7 days as assessed using histology and T2-weighted imaging. DWI could not be used to quantify infarct volume at 7 days because there was no uniform signal in the damaged area. At 7 days the area of infarction actually appeared to be darker in the diffusion-weighted images. The hyperintensity seen in diffusion-weighted images appears to decrease some time between 24 h and 7 days.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798327 TI - Photic stimulation study of changing the arterial partial pressure level of carbon dioxide. AB - To investigate the effect of the level of baseline cerebral blood flow (CBF) on local CBF augmentation by activation, we have used positron emission tomography to measure regional CBF (rCBF) in 12 normal volunteers with and without photic stimulation during hypocapnia, normocapnia, and hypercapnia. The increase in rCBF in the primary visual cortex by photic stimulation was 10.8 +/- 3.1, 18.6 +/- 9.3, and 19.5 +/- 6.1 ml 100 ml-1 min-1 in hypo-, normo-, and hypercapnia, respectively. The increase was significantly smaller in hypocapnia than in normocapnia (p < 0.005). The fractional CBF increase caused by the photic stimulation was the same in all breathing conditions. This result indicates that the magnitude of the CBF increase induced by neuronal activity correlates proportionally with the level of baseline CBF. PMID- 7798324 TI - Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. AB - The implantation of bone morphogenetic protein (BMP) into muscular tissues induces ectopic bone formation at the site of implantation. To investigate the mechanism underlying this process, we examined whether recombinant bone morphogenetic protein-2 (BMP-2) converts the differentiation pathway of the clonal myoblastic cell line, C2C12, into that of osteoblast lineage. Incubating the cells with 300 ng/ml of BMP-2 for 6 d almost completely inhibited the formation of the multinucleated myotubes expressing troponin T and myosin heavy chain, and induced the appearance of numerous alkaline phosphatase (ALP)-positive cells. BMP-2 dose dependently induced ALP activity, parathyroid hormone (PTH) dependent 3',5'-cAMP production, and osteocalcin production at concentrations above 100 ng/ml. The concentration of BMP-2 required to induce these osteoblastic phenotypes was the same as that required to almost completely inhibit myotube formation. Incubating primary muscle cells with 300 ng/ml of BMP-2 for 6 d also inhibited myotube formation, whereas induced ALP activity and osteocalcin production. Incubation with 300 ng/ml of BMP-2 suppressed the expression of mRNA for muscle creatine kinase within 6 h, whereas it induced mRNA expression for ALP, PTH/PTH-related protein (PTHrP) receptors, and osteocalcin within 24-48 h. BMP-2 completely inhibited the expression of myogenin mRNA by day 3. By day 3, BMP-2 also inhibited the expression of MyoD mRNA, but it was transiently stimulated 12 h after exposure to BMP-2. Expression of Id-1 mRNA was greatly stimulated by BMP-2. When C2C12 cells pretreated with BMP-2 for 6 d were transferred to a colony assay system in the absence of BMP-2, more than 84% of the colonies generated became troponin T-positive and ALP activity disappeared. TGF-beta 1 also inhibited myotube formation in C2C12 cells, and suppressed the expression of myogenin and MyoD mRNAs without inducing that of Id-1 mRNA. However, no osteoblastic phenotype was induced by TGF-beta 1 in C2C12 cells. TGF beta 1 potentiated the inhibitory effect of BMP-2 on myotube formation, whereas TGF-beta 1 reduced ALP activity and osteocalcin production induced by BMP-2 in C2C12 cells. These results indicate that BMP-2 specifically converts the differentiation pathway of C2C12 myoblasts into that of osteoblast lineage cells, but that the conversion is not heritable. PMID- 7798328 TI - Cerebral blood flow and metabolic responses to sustained hypercapnia in awake sheep. AB - This investigation determined the effects of sustained hypercapnia on cerebral blood flow (CBF; radiolabeled microspheres), cerebral metabolic rates for O2 and glucose (CMRO2 and CMRglc), and brain water content in conscious sheep instrumented with aortic, left ventricular, vena cava, and brain sagittal sinus catheters. PaCO2 was elevated from 38 +/- 3 to 53 +/- 3 (mean +/- SD) mm Hg and PaO2 from 109 +/- 7 to 131 +/- 4 mm Hg for 96 h in an environmental chamber. Hypercapnia did not alter sheep behavior, food and water intake, arterial pressures, core temperature, or brain lactate release. Total and regional CBF and CBF/CMRO2 reached peak values at 1 h and then readjusted, to stabilize at lower, but still elevated levels at 24 h and thereafter. CMRO2 and CMRglc increased at 6 h and thereafter during hypercapnia. PaCO2, CBF, CMRO2, and CMRglc remained elevated at 3 h after restoration to room air, while CBF/CMRO2 returned to the control value. Frontal and occipital lobe wet-to-dry weight ratios increased modestly but significantly after hypercapnic exposure. It is concluded that sustained hypercapnia induces stable and nonadapting increases in both CBF and brain metabolism that persist for at least 3 h after restoration to room air in association with hypoventilization and modest elevations of brain water. PMID- 7798330 TI - Simultaneous measurements of pial arteriolar diameter and laser-Doppler flow during somatosensory stimulation. AB - We simultaneously measured pial arteriolar diameter and changes in cortical blood flow during activation of the somatosensory cortex by sciatic nerve stimulation. The pial vasculature was visualized with a closed-cranial window technique in chloralose-anesthetized rats (n = 13). Local blood flow was monitored with laser Doppler flowmetry. During stimulation of the sciatic nerve (0.2 V, 5 Hz, 20 s), vascular diameter and laser-Doppler flow consistently displayed similar response profiles. With 0.5-ms stimulation pulses, the responses showed an initial peak followed by a smaller but sustained plateau dilation. In contrast, 5-ms pulses evoked a monotonically rising response. Our results support the concept that pial arteriolar diameter changes reflect cortical blood flow responses during somatosensory stimulation. PMID- 7798329 TI - Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. AB - 13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 +/- 0.19 mumol min-1 g-1 (mean +/- SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of alpha-ketoglutarate/glutamate exchange was 57 +/- 26 mumol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that alpha-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 mumol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 mumol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the brain oxygen consumption was estimated to be 2.14 +/- 0.48 mumol min-1 g-1 (5.07 +/- 1.14 ml 100 g-1 min-1; n = 4), and the rate of brain glucose consumption was calculated to be 0.37 +/- 0.08 mumol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values. PMID- 7798331 TI - Role of the cerebellar fastigial nucleus in the physiological regulation of cerebral blood flow. AB - Local cerebral blood flow (ICBF) was measured with [14C]iodoantipyrine in conscious, unrestrained rats during electrical stimulation of the fastigial nucleus (FN). Electrode position in the FN was determined by blood pressure (MABP) responses to stimulation under anesthesia. In nine rats in which MABP responses had been variable under anesthesia, bipolar stimulation (50 Hz, 0.5 ms, 1 s on/1 s off) with currents of 30-100 microA after recovery from anesthesia produced stereotypic behavior but little effect on MABP and ICBF. In seven other conscious rats currents could be raised to 75-200 microA without inducing seizures, resulting in sustained MABP elevations during the ICBF measurement and significantly increased ICBF in the sensory-motor (+45%), parietal (+31%), and frontal cortices (+56%) and the caudate-putamen (+27%) above control values (n = 9). Glucose utilization, measured with [14C]deoxyglucose, in rats similarly stimulated was significantly increased in six structures, including some of the above, indicating increases in ICBF due to metabolic activation. Unilateral or bilateral electrolytic lesions of the FN, placed 6-7 days before ICBF measurement, had negligible effects on resting ICBF and on autoregulation in conscious rats. These results fail to support a specific role for the FN in physiological regulation of cerebral blood flow in unanesthetized rats. PMID- 7798332 TI - The role of angiotensin II in the regulation of blood flow to choroid plexuses and cerebrospinal fluid formation in the rat. AB - The effect of peripherally administered angiotensin II (AII) on blood flow to choroid plexuses was examined in pentobarbital-anesthetized rats. The indicator fractionation method with 123I- or 125I-N-isopropyl-p-iodoamphetamine as the marker was employed to measure blood flow. Basal blood flow to choroid plexus of the lateral cerebral ventricle (LVCP) (3.19 +/- 0.23 ml g-1 min-1) was lower than that to choroid plexuses of the third (3VCP) and fourth (4VCP) ventricles (3.90 +/- 0.38 and 3.95 +/- 0.36 ml g-1 min-1, respectively). The effect of AII on choroidal blood flow varied depending on peptide dose and anatomical location of the choroidal tissue. AII infused intravenously at rates of 30 and 50 ng kg-1 min 1 decreased blood flow to both LVCP and 4VCP by 12-20%. Both lower (10 ng kg-1 min-1) and higher (100 and 300 ng kg-1 min-1) AII doses did not alter blood flow to LVCP and 4VCP. Blood flow to the 3VCP was not affected by any dose of the peptide used. In comparison, blood flow to cerebral cortex increased by 33% during intravenous AII infusion at a rate of 300 ng kg-1 min-1. The choroidal blood flow-lowering effect of moderate AII doses was abolished by both AT1 (losartan) and AT2 (PD 123319) receptor subtype antagonists (3 mg kg-1 i.v.). To determine whether the hemodynamic changes observed in choroid plexuses with moderate AII doses influence CSF formation, the ventriculocisternal perfusion was performed in rats (under the experimental conditions described) with Blue Dextran 2000 as the indicator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798333 TI - Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle. AB - Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (Bmax) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (KD) for flumazenil in five normal subjects. The steady-state approach was used injecting the tracer as a bolus of high specific activity. In each subject two studies were carried out. The first study was performed at essentially zero receptor occupancy, the tracer alone study. The second study was performed at a steady-state receptor occupancy of about 50%, achieved by a prolonged constant infusion of nonlabeled ("cold") flumazenil starting 2h before the bolus tracer injection and continuing until the end of scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma tracer curves, calibrated in the same units of radioactivity per millimeter, were analyzed in two ways: (a) by the noncompartmental (stochastic) approach making no assumptions regarding number of compartments in the tissue, and (b) by the single-compartment approach assuming rapid exchange (mixing) of tracer between all tissue compartments. The noncompartmental and the compartmental analyses gave essentially the same values for the distribution volume of the tracer, the parameter used for quantitation of the Bz receptor. As the compartmental approach could be applied to a shorter observation period (60 min instead of 120 min) it was preferred. The five subjects had a mean KD value of 12 nM/L of water and Bmax values of the grey matter ranging from 39 +/- 11 in thalamus to 120 +/- 14 nM/L of brain in occipital cortex. Most previous studies have been based on the pseudoequilibrium approach using the brain stem as a receptor-free reference region. This yields practically the same KD but lower Bmax values than the steady-state approach presented here. PMID- 7798334 TI - Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. AB - The expression of interleukin-6 (IL-6) mRNA in the focal ischemic rat cortex was studied by means of Northern hybridization. IL-6 mRNA was induced after permanent occlusion of the middle cerebral artery, reached a significant level at 3 h, and peaked at 12 h, i.e., approximately 10-fold increase in the ischemic zone compared with the nonischemic cortex or sham-operated controls. The increased IL 6 mRNA was elevated for at least 24 h. Low levels of IL-6 mRNA were detected in sham-operated rats or in the contralateral nonischemic cortex. The expression of c-fos and zif268 mRNAs, two early response genes, was rapid (increased by 1 h postischemia) and transient (returned to basal levels by 24 and 12 h, respectively), clearly having different kinetic patterns from that of IL-6 mRNA. The early response kinetic pattern of c-fos and zif268 mRNAs in focal ischemia suggests their transcriptional regulatory roles in response to ischemic insult, while the delayed induction pattern of IL-6 mRNA suggests a role for this pleiotropic cytokine in the inflammatory response to the focal ischemic damage of the brain. PMID- 7798336 TI - Autoregulatory plateau: does it exist? PMID- 7798335 TI - Contribution of cerebral edema to the neuronal salvage elicited by stimulation of cerebellar fastigial nucleus after occlusion of the middle cerebral artery in rat. PMID- 7798337 TI - Concomitant EEG, lactate, and phosphorus changes by 1H and 31P NMR spectroscopy during repeated brief cerebral ischemia. AB - Pilots of high-performance aircraft are subject to transient loss of consciousness due to cerebral ischemia resulting from sudden high gravitational stress. To assess the effects of gravitational stress-induced blackout on cerebral metabolism and electrical function, we developed an animal model in which global cerebral ischemia is produced repeatedly at short intervals. Rats were prepared by ligation of subclavian and external carotid arteries and the right carotid artery was cannulated bidirectionally to measure circle of Willis and systemic pressures. Ischemia was induced by inflation of an occluder about the left carotid artery. Interleaved 31P and 1H NMR spectra were acquired on a 4.7-T Biospec system simultaneously with EEG recordings. We report results from 20 experiments of 30-min duration in which rats were subject to 30 1-min ischemia:reflow cycles of 10I:50R, 20I:40R, 30I:30R, and 40I:20R [numbers are seconds of ischemia (I) and reflow (R) during each 1-min cycle]. During ischemia the graded delivery of the ischemic insult permitted direct correlations between 2- to 5- and 7- to 20-Hz EEG activity and progressive changes in pH, lactate, ATP, phosphocreatine (PCr) and Pi. The best correlations were found between EEG activity and pH and PCr; correlation coefficients ranged from 0.93 to 0.95. A loss of EEG activity was observed without significant sustained energy loss in all but the most severe cycle. PMID- 7798338 TI - Induction of CL100 protein tyrosine phosphatase following transient forebrain ischemia in the rat brain. AB - Protein tyrosine phosphorylation is thought to play an important role in the regulation of neural function. To elucidate the role that protein tyrosine phosphatases (PTPs) may play in the postischemic brain, PTPs expressed in regions of the rat brain vulnerable to transient forebrain ischemia were examined. With the reverse-transcriptase polymerase chain reaction using degenerate primers, three PTPs, STEP, PTP delta, and SH-PTP2, were identified. They were expressed in the hippocampus 12 h after transient ischemia for 20 min. During the reperfusion period, the mRNA levels of these PTPs were not different from those in sham operated rats. In contrast, a fourfold increase in the mRNA level of CL100 (3CH134), a PTP that is inducible by oxidative stress, was detected by Northern blotting in the hippocampus and cerebral cortex 1 h after the onset of reperfusion. In situ hybridization histochemistry showed a slight increase in the level of CL100 mRNA in neuronal cells in the hippocampus and cortex of postischemic rats compared to control rats. These findings suggest that PTPs play a role in the normal function of the hippocampus and cerebral cortex and demonstrate that ischemia induced CL100 expression. PMID- 7798339 TI - Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance. AB - Pretreatment of the gerbil brain with a 2-min period of sublethal ischemia protects against neuronal damage following a subsequent 3-min period of ischemia, which normally destroys pyramidal neurons in the CA1 region of the hippocampus. To clarify the role of superoxide dismutase (SOD) in this ischemic tolerance, we immunohistochemically investigated the alterations in copper-zinc SOD (CuZnSOD) and manganese SOD (Mn-SOD) in the gerbil hippocampus following 3-min ischemia with or without the first mild ischemia. Normal hippocampus showed an intense CuZnSOD immunostaining in pyramidal neurons but relatively less MnSOD immunostaining. MnSOD, but not CuZnSOD, immunoreactivity increased after the first ischemia. Both CuZnSOD and MnSOD immunoreactivities decreased throughout the hippocampus 4 h after 3 min of ischemia both with and without the first ischemia. The immunostaining recovered in resistant regions (CA3 and dentate gyrus) after 1 day in both groups and in the pretreated CA1 after 2 days. Without pretreatment, however, the immunostaining never recovered in the vulnerable CA1 region. The results suggest that ischemic tolerance is induced in part by enhanced synthesis of MnSOD in the tolerance-acquired hippocampus. Both CuZnSOD and MnSOD immunoreactivities decreased after the second ischemia even in the pretreated hippocampus in the early reperfusion periods, but ischemic tolerance facilitated the recovery from the postischemic reductions in SOD immunoreactivity. PMID- 7798340 TI - A simple method for evaluation of superoxide radical production in neural cells under various culture conditions: application to hypoxia. AB - To evaluate the potential deleterious influence of oxygen-derived free radicals following hypoxia in a model of primary culture of neurons obtained from the fetal rat brain, superoxide radicals were measured as a function of time in the extracellular medium. Neuronal cells were grown for 8 days in the presence or absence of serum, then incubated in a buffered Krebs-Ringer solution containing 60 microM acetyl-cytochrome c. The rate of superoxide radical formation was quantified spectrophotometrically by measuring the specific reduction of acetyl cytochrome c. Under normoxic conditions (95% air-5% CO2), basal production of superoxide that increased with time was recorded. It was significantly more pronounced in cells grown in serum-free medium. Under both culture conditions, acute hypoxia (95% N2-5% CO2) for 6 h increased superoxide radical amounts in the extracellular medium, and they were still enhanced 3 h after reoxygenation. The addition of superoxide dismutase to the incubating medium abolished the detection of superoxide radicals. The present study describes a new reliable method for superoxide radical measurement in cells in vitro and demonstrates hypoxia/reoxygenation-induced overproduction of superoxide in cultured neurons that may account for cell injury. PMID- 7798341 TI - The influence of acidosis on hypoglycemic brain damage. AB - The objective of the study was to explore whether hypoglycemic brain damage is affected by super-imposed acidosis. To that end, animals with insulin-induced hypoglycemic coma, defined in terms of a negative DC potential shift, massive release of K+, or cellular uptake of Ca2+, were exposed to excessive hypercapnia (PaCO2 approximately 200 or approximately 300 mm Hg) during the last 25 min of the 30-min coma period. Animals were allowed to survive for 7 days before their brains were fixed by perfusion, and the cell damage was assessed by light microscopy. Other animals were analyzed with respect to changes in extracellular pH (pHe) or extracellular K+ or Ca2+ concentrations (K+e and Ca2+e, respectively). The total CO2 content (TCO2) was also measured to allow derivation of intracellular pH (pHi). The increase in PaCO2 to 190 +/- 15 and 312 +/- 23 mm Hg (means +/- SD) reduced the pHe from a predepolarization value of approximately 7.4 and a postdepolarization value (after the first 5 min of coma) of approximately 7.3 to 6.8 and 6.7, respectively. The corresponding mean pHi values were 6.7 and 6.5. The hypercapnia did not alter the K+e, which rose to 50-60 mM at the onset of hypoglycemic coma, but it increased the Ca2+e from approximately 0.05 to 0.10-0.16 mM. Normocapnic animals with induced hypoglycemic coma of 30 min duration showed the expected neuronal lesions in the neocortex, hippocampus, and caudoputamen. Hypercapnia clearly aggravated this damage, particularly in the caudoputamen, subiculum, and CA1 region of the hippocampus, and caused additional damage to cells in the CA3 region and piriform cortex. A rise in CO2 tension from approximately 200 to 300 mm Hg did not further aggravate the damage. The results thus demonstrate that relative moderate acidosis aggravates damage that is believed to be mostly neuronal, sparing glia cells and vascular tissue. PMID- 7798342 TI - Tirilazad pretreatment improves early cerebral metabolic and blood flow recovery from hyperglycemic ischemia. AB - Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglycemia, pretreatment with the 21-aminosteroid tirilazad mesylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg/kg plus 0.2 mg/kg/h; n = 8) or vehicle (n = 8). Hyperglycemia (400-500 mg/dl) was produced prior to 30 min of global incomplete cerebral ischemia. Intracellular pH and high energy phosphates were measured by phosphorus magnetic resonance spectroscopy. During ischemia, microsphere determined CBF decreased to 8 +/- 4 ml min-1 100 g-1 and intracellular pH decreased to 5.6 +/- 0.2 in both groups. During the first 20 min of reperfusion, ATP partially recovered in the vehicle group to 57 +/- 21% of baseline, but then declined progressively in association with elevated intracranial pressure. By 30 min, ATP recovery was greater in the tirilazad group (77 +/- 35 vs. 36 +/- 19%), although postischemic hyperemia was similar. By 45 min, the tirilazad group had a higher intracellular pH (6.5 +/- 0.5 vs. 5.9 +/- 0.6) and a lower intracranial pressure (18 +/- 6 vs. 52 +/- 24 mm Hg). By 180 min, blood flow and ATP were undetectable in seven of eight vehicle-treated dogs, whereas ATP was > 67% and pH was > 6.7 in six of eight tirilazad-treated dogs. Thus, tirilazad acts during early reperfusion to prevent secondary metabolic decay associated with severe acidotic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798343 TI - Labeling of metabolic pools by [6-14C]glucose during K(+)-induced stimulation of glucose utilization in rat brain. AB - [6-14C]Glucose is the tracer sometimes recommended to assay cerebral glucose utilization (CMRglc) during transient or brief functional activations, but when used to study visual stimulation and seizures in other laboratories, it underestimated CMRglc. The metabolic fate of [6-14C]glucose during functional activation of cerebral metabolism is not known, and increased labeling of diffusible metabolites might explain underestimation of CMRglc and also reveal trafficking of metabolites. In the current studies cerebral cortex in conscious rats was unilaterally activated metabolically by KCl application, and CMRglc was determined in activated and contralateral control cortex with [6-14C]glucose or 2 [14C]deoxy-glucose ([14C]DG) over a 5- to 7-min interval. Local 14C concentrations were determined by quantitative autoradiography. Labeled precursor and products were measured bilaterally in paired cortical samples from funnel frozen brains. Left-right differences in 14C contents were small with [6 14C]glucose but strikingly obvious in [14C]DG autoradiographs. CMRglc determined with [6-14C]glucose was slightly increased in activated cortex but 40-80% below values obtained with [14C]DG. [14C]Lactate was a major metabolite of [6 14C]glucose in activated but not control cortex and increased proportionately with unlabeled lactate. These results demonstrate significant loss of labeled products of [6-14C]glucose from metabolically activated brain tissue and indicate that [14C]DG is the preferred tracer even during brief functional activations of brain. PMID- 7798344 TI - Leadership: a new conception. AB - The article summarizes the common wisdom regarding leadership that informs our present understanding of leadership. It articulates a new understanding of leadership, referred to as the postindustrial paradigm of leadership; comments on this new paradigm; contrasts it with the industrial paradigm of leadership; and ends with some comments on leadership as an episodic affair. PMID- 7798345 TI - Transformational leadership: the feminist connection in postmodern organizations. AB - The article describes the changes occurring in the world and organizations and argues that the contemporary theory of transformational leadership can provide guidance for nursing leaders, who are predominantly women. Transformational leadership is defined and described. The feminist literature is briefly reviewed. A comparison of the attributes of women, who are constructed knowers, and those of transformational leaders is made, including the web of inclusion, caring, moral responsibility, reciprocity and cooperation, integration of voices, intuition, and hierarchic and patriarchal paradigms. It is argued that a new way of leading and new organizational structures are emerging that will provide a favorable environment for female leaders. PMID- 7798346 TI - A challenge to nursing: promoting followers as well as leaders. AB - It is believed that 70% of our lives is spent in the role of follower. Even so, the focus in formal education and seminars remains leadership issues because of the unfavorable stereotypes that accompany the term follower. Nurturing effective followership requires doing away with the misconception that leaders do all the thinking and followers mindlessly heed orders. Can followers and leaders ever be deemed separate but equal? It is vital to understand that, without effective followers in nursing, our leaders face severe limitations. Current leaders and educators must share and promote the vision of enlightened followership if nursing is to achieve its potential. PMID- 7798348 TI - Ethical aspects of transformational leadership. AB - The requirements of leadership in the current environment of health care reform necessitate a clear distinction between leadership and management, an alteration in traditional leadership roles, and an evaluation of the knowledge and skills needed to address the ethical issues that arise from such reform. Transformational leadership is well suited to the current climate in health care because of the manner in which it actively embraces and encourages innovation and change. The article explores the elements of transformational leadership, describes the need for transformational leaders to be cognizant of the ethical aspects of their roles, and outlines the responsibilities of transformational leaders as moral agents. PMID- 7798347 TI - The coaching, precepting, and mentoring roles of the leader within an organizational setting. AB - The article examines the use of learning relationships to develop followers. The concepts of mentoring, precepting, and coaching are differentiated. Leader values are examined. The process of performing an environmental assessment and assessing organizational values is explored in a case study format. Four possible outcome assessments and the role of the leader are described. The use of theory and concepts to create change and to structure win-win situations is explored. PMID- 7798349 TI - Leadership preparation: an examination of master's degree programs in nursing. AB - The study was designed to examine the differences between leadership and management and to compare the leadership content in a sample of graduate programs in nursing with those conceptual differences. A review of seven components contained within the National League for Nursing self-study reports of 10 accredited programs in four regions of the country was conducted. Data analysis revealed that leadership, as defined in the literature, was included in most curriculum components in the graduate programs studied. The emphasis in the 10 graduate programs analyzed clearly was leadership development rather than management preparation. PMID- 7798350 TI - Organizational innovations that nourish staff leadership. AB - Health care is experiencing a paradigm shift that has the potential to redefine traditional roles, systems, and practices. At Albert Einstein Medical Center in Philadelphia, Pennsylvania, the nursing organization has capitalized on this potential and has been energized by the array of opportunities for innovation and experimentation. The results of these efforts suggest that many of these changes not only are positive approaches to patient care but also promote staff leadership and an entrepreneurial spirit at the front line. PMID- 7798351 TI - The arts and humanities: a creative approach to developing nurse leaders. AB - There are many ways by which leadership skills can be developed, but an effective approach that is rarely considered by educators, administrators, or individuals is the use of the arts and humanities. The article explores the nature of leadership and ways to develop leadership skills. It then examines how the humanities relate to leadership development and provides specific examples of arts and humanities that individuals can use in their quest to evolve as effective leaders. PMID- 7798352 TI - A decade of nursing leadership research. AB - A review of the published nursing leadership research from 1983 to 1993 is presented. The review identifies three categories of research: predicting leadership, leadership development, and leadership effectiveness. Comparisons are made with a previous research review. Recommendations for future research include the relationship between leader and follower, comparison studies of leaders in multiple settings, further analysis of mentorship, continued qualitative analysis, and quantitative research utilizing established instruments. As the new leadership roles of nurse leaders emerge in health care reform, so will new issues for future research. PMID- 7798353 TI - Leadership for the future. AB - Leaders are responsible for guiding others through a future that may be anticipated but is ultimately unknown. In addition, leaders are responsible for creating a positive future. If nurse leaders are to be successful in this process, they would benefit from knowing trends that are projected for the future, reflecting on the kinds of skills that are needed to meet the challenges presented by those trends, and proposing strategies that can be used for effective leadership in our uncertain future. PMID- 7798354 TI - Leadership: can it be holistic? AB - The article looks at new trends toward holistic leadership as opposed to older models focused on the tasks of managers. Transformational leadership and Heider's leadership by Tao are given as illustrations, as is the recent upsurge of interest in the spiritual aspect of care. It is noted that leadership is provided in many settings among persons with and without organizational managerial positions. The need for holistic leadership in a time of environmental flux and unpredictability is discussed. PMID- 7798355 TI - The temporoparietal fascial flap in reconstruction of the cranio-maxillofacial area. AB - An improved understanding of the vascular supply of the layers of the temporal fossa has increased the potentiality of reconstructive techniques involving this area. Each separate vascularized layer of this region can be used, yet the temporoparietal fascial flap is the more useful for treating a wide range of composite defects. It represents an ultra thin coverage which is useful in resurfacing exposed bone, tendons and vital structures such as nerves and vessels, in providing neovascularity as a recipient graft bed and in providing coverage or lining in major facial reconstructions. We describe our experience with the temporoparietal fascial flap which represents our choice for reconstructing composite defects in orbital, malar, auricular and cheek areas when what is required is a thin, pliable, well vascularized flap to carry a scalp or skin graft, to resurface exposed cartilage, bone and nerve, and to fill soft tissue contour defects. Illustrative cases from the authors' clinical experience are presented, to demonstrate various combinations of the temporoparietal fascial pedicle with other tissues in the reconstruction of the ear, eyebrows, eyelids, malar, cheek and parotid areas. PMID- 7798356 TI - Early evaluation of necrotizing fasciitis with use of CT. AB - Gas bubbles are one of the important signs in the clinical diagnosis of necrotizing fasciitis, and radiographs are mandatory. An instance where gas bubbles not found on the plain radiographs were clearly shown by CT, which is a useful method for close monitoring and decompression of gas bubbles situated deeply in the spaces of the maxillo-facial and neck regions. PMID- 7798357 TI - Incidence of velopharyngoplasty following various techniques of palatoplasty. AB - A total of 474 patients with cleft palates were treated at the Department for Maxillofacial Surgery of Rostock University from 1971 to 1991. In 145 cases velopharyngoplasty was indicated. Primary velopharyngoplasty was performed on 36 and secondary velopharyngoplasty on 109 patients. In our opinion today primary velopharyngoplasty should be the exception. Intravelar veloplasty according to Kriens (1970) created particularly favorable conditions for good velar function so that secondary pharyngoplasty was only rarely indicated. Secondary pharyngoplasty should be performed and timed only in agreement with the speech therapist. PMID- 7798358 TI - The popliteal pterygium syndrome: an analysis of two families. AB - The popliteal pterygium syndrome is characterized by multiple anomalies of the face, genito-urinary system and extremities with autosomal dominant inheritance with variable expression. Also sporadic cases probably based upon spontaneous mutation can be recognized. The plastic, orthopaedic, and maxillofacial surgeon should be aware of the variable nature of the syndrome and should consult a medical geneticist. A coordinated team approach appears to be most adequate for diagnosis, counselling and treatment. PMID- 7798359 TI - Evaluation of the slot osteosynthesis technique in mandibular advancement. With focus on occlusion and lower lip sensibility. AB - The slot osteosynthesis technique (SLOT) was evaluated in 25 mandibular advancements. SLOT was successfully used to readjust skeletal and occlusal malpositioning in 48% of the cases. Neurosensory tests in the lower lip and chin region revealed a low disturbance rate (immediately postsurgery 20% of patients, at 7 months 8%). This may be due to the specific splitting and fixation techniques applied. PMID- 7798360 TI - A prospective study on changes in the sensibility of the oral mucosa and the mucosa of the upper lip after Le Fort I osteotomy. AB - A prospective study on 21 patients was performed in order to investigate the changes in the sensibility of the oral mucosa and the mucosa of the upper lip after a Le Fort I osteotomy. Patients were followed-up 1 month, 3 months and 6 months postoperatively. The sensibility of the mucosa was tested using electrical sensimetry (Laitinen, 1987). The teeth were tested with carbon dioxide snow (Obwegeser and Steinhauser, 1963). A picture of the marked hypoaesthetic area was performed and magnified 1:1 if a hypoaesthesia of the cutaneous distribution of the infraorbital nerve was found. The area was measured using a Macintosh II CX computer. It was demonstrated, that after 3 months the infraorbital nerve regained its function completely. The greater palatine nerve and the posterior superior alveolar nerve demonstrated an incomplete recovery of sensory function after 6 months. After 6 months 92.8% of the teeth reacted to carbon dioxide snow. Within the first 6 months postoperatively, no pulpe necrosis was observed. No correlation could be found between the amount of anterior maxillary movement and the degree of hypoaesthesia of the infraorbital nerve. Dentate Le Fort I osteotomies showed a better sensory regeneration of the greater palatine nerve than edentulous Le Fort I osteotomies. After Le Fort I osteotomies in 2 parts, more hypoaesthesia of the greater palatine nerve was observed than after Le Fort I osteotomies in 1 part. After miniplate osteosynthesis, more hypoaesthesia of the posterior superior alveolar nerve was observed than after wire osteosynthesis. The results are discussed and compared with the results found in the literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798361 TI - Clinical investigation into the incidence of direct damage to the lingual nerve caused by local anaesthesia. AB - The aim of this study was to investigate the amount of damage to the lingual nerve by mandibular block anaesthesia alone. For this purpose the records of 12,104 patients in whom mandibular block anaesthesia was administered without any type of surgery were reviewed. The reason for treatment in those patients was, in 72.4% fillings and crown preparations, in 27.13% periodontal procedures and in 0.30% other treatment. The records showed a lingual sensory disturbance in 18 out of 12,104 patients (0.15%). In 17 out of these 18 patients the tongue sensation recovered after a period of 6 months. Only in one patient (0.008%) was there a slight sensory diminution of the tongue, even after one year. PMID- 7798363 TI - Laser Doppler imaging of axial and random pattern flaps in the maxillo-facial area. A preliminary report. AB - Objective, non-invasive examination, techniques in addition to clinical parameters, are required to follow-up the wound healing of flaps. With the new laser Doppler Scanner (LDI DIM 1.0 Lisca Development AB, Sweden) it is possible, for the first time, to measure and image the microcirculation continuously, non invasively and without contact with the wound, in an area of 12 cm square maximum. We performed measurements and simultaneous two-dimensional imaging of the microcirculation 24, 48, 72 h and 5 and 14 days postoperatively in 20 patients, who had had reconstruction procedures performed using random or axial pattern flaps. The perfusion diagrams were correlated to the clinical appearance. Necrotic areas, venous stasis and normal course of wound healing can be clearly visualized and differentiated from one another. The new laser Doppler imaging system seems to be an excellent aid for following up and planning of flaps in plastic and reconstructive surgery. PMID- 7798364 TI - Lingual thyroid: a new surgical approach--a case report. AB - Ectopic lingual thyroid is a rare developmental anomaly, presenting in the adult with obstructive symptoms during respiration, deglutition and speech. The main therapeutic issue after exact diagnosis is the restoration of thyroid function, and surgical intervention, when necessary, has to deal with problems related to the site and function of the ectopic gland. A case of a 25-year-old female with dyspnoea and dysphagia due to a 3 x 4 cm ectopic lingual thyroid, excised by an original peroral approach via a mandibular midline osteotomy, is reported. Our surgical technique is described and the diagnostic and therapeutic problems are reviewed. PMID- 7798362 TI - Autogenous transplantation of third molars in irradiated jaws--a preliminary report. AB - Our experience with third molar autotransplants in 2 patients, into an area irradiated at an early age, is described and discussed. It is shown that such autotransplantations are possible. PMID- 7798366 TI - Penetration of the skull base by dissecting keratocyst--Jackson et al. J. Craniomaxillofac. Surg. (1993) 21, 319-325. PMID- 7798365 TI - The surgical approaches to nasopharyngeal angiofibroma. AB - After a short summary of the aetiopathogenesis, the routes of extension and the diagnostic features of nasopharyngeal angiofibroma, the importance of early diagnosis and careful surgical planning is underlined. In particular the extension and topographic localization allows the choice of the best approach to optimize surgical radicality--the prime concern in the treatment of nasopharyngeal angiofibroma. Different surgical approaches are proposed for the tumour removal according to our experience in 17 patients. PMID- 7798367 TI - Penetration of the skull base by dissecting keratocyst--Jackson et al. J. Craniomaxillofac. Surg. (1993) 21, 319-325. PMID- 7798368 TI - Developmental outcome of very low birth weight infants as a function of biological risk and psychosocial risk. AB - The relative contribution of biological and psychosocial risk factors to developmental outcome of 102 very low birth weight infants (< 1500 g) was delineated through 24 months corrected age. Biological risk, assessed by the Neurobiologic Risk Score (NBRS), accounted for significant amounts of variance in Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at the 6-, 15-, and 24-month assessment points. Psychosocial risk, reflected in maternal appraisals of daily stress, accounted for a significant increment in cognitive outcome (MDI), over and above that accounted for by the NBRS, at each assessment point. Cognitive functioning at each assessment point differed as a function of biological risk and psychosocial risk status. The findings are discussed in terms of maternal stress as a marker of, and salient intervention target for, caregiving environments that can maximize or minimize the effects of biological vulnerability. PMID- 7798369 TI - What do minority elementary students understand about the causes of acquired immunodeficiency syndrome, colds, and obesity? AB - Elementary school-age children's conceptual understanding and factual knowledge about the causes of acquired immunodeficiency syndrome (AIDS), colds, and obesity are poorly understood, particularly among black children living in low-income, urban neighborhoods. We examined minority children's conceptual understanding about the causes of these illnesses. In addition, children's knowledge and misconceptions about the causal agents of AIDS, colds, and obesity were investigated. A developmentally based, semistructured interview was developed to measure children's level of understanding about the causes of each condition. Interviews were conducted with 239, predominately black, first, third, and fifth grade students attending two public elementary schools in a low income city in northern California. Interviews were verbally administered and tape recorded for later verbatim transcription. Children's responses to questions about causality first were scored based on their level of conceptual sophistication. Responses then were assigned to thematic categories reflecting the children's factual knowledge about the causes of AIDS, colds, and obesity. Increases in grade level were associated with higher scores for causality of AIDS (p < .0001), colds (p < .0001), and obesity (p < .01). In all three conditions, causality scores increased between first and fifth grades, but did not significantly vary between third and fifth grades. Gender, socioeconomic status, and number of adults living in the household were not significantly associated with causality scores. Within each grade, the finding of lower causality scores for AIDS, as compared to colds and obesity, points out the need for developmentally appropriate explanations to children about the causes of AIDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798370 TI - School achievement and failure in very low birth weight children. AB - The extent to which low birth weight confers a risk for poor school function remains an important question. Children (N = 1868) in four birth weight categories [extremely low birth weight (ELBW; children weighed < or = 1000 g at birth, n = 247), other very low birth weight (1001 through 1500 g, n = 364), heavier low birth weight (1501 through 2500 g, n = 724), and normal birth weight (NBW > 2500 g, n = 533)] were compared on indicators of school achievement which included grade failure, placement in special classes, classification as handicapped, and math and reading achievement scores (Woodcock-Johnson Battery). Our results indicate that as birth weight decreases, the prevalence of grade failure, placement in special classes, and classification as handicapped increases, even when controlling for maternal education and neonatal stay. Moreover, ELBW children score lower than all other birth weight groups on math and reading achievement tests. Even among children with IQ scores above 85, ELBW children still obtain lower math scores than NBW children, suggesting the potential for future educational needs. PMID- 7798371 TI - Hypnosis in the prevention of chemotherapy-related nausea and vomiting in children: a prospective study. AB - To study the effectiveness of hypnosis for decreasing antiemetic medication usage and treatment of chemotherapy-related nausea and vomiting in children with cancer, we conducted a prospective, randomized, and controlled single-blind trial in 20 patients receiving chemotherapy for treatment of cancer. Patients were randomized to either hypnosis or standard treatment. The hypnosis group used hypnosis as primary treatment for nausea and vomiting, using antiemetic medication on a supplemental (p.r.n.) basis only, whereas the control group received a standardized antiemetic medication regimen. Nausea, vomiting, and p.r.n. antiemetic medication usage were measured during the first two courses of chemotherapy. Anticipatory nausea and vomiting were assessed at 1 to 2 and 4 to 6 months postdiagnosis. Patients in the hypnosis group used less p.r.n antiemetic medication than control subjects during both the first (p < .04) and second course of chemotherapy (p < .02). The two groups did not differ in severity of nausea and vomiting. The hypnosis group experienced less anticipatory nausea than the control group at 1 to 2 months postdiagnosis (p < .02). Results suggest self hypnosis is effective for decreasing antiemetic medication usage and for reducing anticipatory nausea during chemotherapy. PMID- 7798372 TI - Age differences in parent and child responsibilities for management of cystic fibrosis and insulin-dependent diabetes mellitus. AB - Mothers (n = 26) of children and young adolescents (ages 4 to 14) with insulin dependent diabetes mellitus (IDDM) and mothers (n = 26) of children and young adolescents with cystic fibrosis (CF) (ages 4 to 14) described family responsibilities for treatment-related tasks and their children's general independence. Contrary to prediction, children and adolescents with CF and IDDM demonstrated comparable levels of independence concerning treatment-related responsibilities and their general adaptive behavior. As hypothesized, older children assumed higher levels of independence in managing their conditions, as well as sharing of treatment-related responsibilities with their parents. However, parents, especially mothers, continued to be very involved in most tasks, even for young adolescents. Independence in assuming treatment-related responsibilities was highly related to general independence among children and adolescents with both conditions. Children's independence in chronic illness management was not related to help mothers received from others as measured by the frequency and/or number of people helping. Findings have implications for pediatricians' monitoring and support of adaptive family responsibilities for chronic illness management. PMID- 7798373 TI - Managed care: good or bad news for children? PMID- 7798374 TI - Behavioral assessment and treatment of pediatric feeding disorders. AB - Pediatric feeding disorders are estimated to occur in as many as one in every four infants and children, and when serious can require numerous, costly and sustained interventions. For over a decade research has cumulated evidence on the contributions of Behavior Analysis in understanding and remediating some types of pediatric feeding disorders. The systematic use of this body of evidence in conjunction with other approaches (medical, nutrition, occupational therapy, physical therapy, and so forth) is being carried out on an inpatient treatment unit at the Kennedy Krieger Institute. Key aspects are described here, including direct observation behavior assessment, approaches for increasing and decreasing feeding behavior, skill acquisition, transfer of treatment gains, and parent training. The results based on case studies and overall program evaluation indicate that medically complicated, severe feeding disorders can be treated successfully in a few months with a multidisciplinary approach which incorporates behavioral procedures. PMID- 7798375 TI - Distribution of histamine-, 5-hydroxytryptamine-, and tyrosine hydroxylase immunoreactive neurons and nerve fibers in developing rat brain. AB - Although the general patterns of the developing histaminergic system in the rat brain are known, no comparative studies between the development of the brain histaminergic system and the development of other neuroactive substances have yet been published. Interestingly, separate immunohistochemical studies on the development of the 5-HT system and on the catecholaminergic system in the rat imply common features in the different aminergic systems. Therefore, the spatial distribution of histamine-immunoreactive (HA-ir) neurons and nerve fibers was compared to the distribution of 5-hydroxytryptamine (5-HT)-, and tyrosine hydroxylase-immunoreactive (TH-ir) ones in the developing rat brain between embryonic days 12 (E12) and 20 (E20) by using a double-immunostaining method. The high-pressure liquid chromatography (HPLC) fluorometric method was used for determination of histamine concentration in different brain regions during the same period of development and synthetic oligonucleotide probes complementary to the rat histidine decarboxylase (HDC) to determine the origin of HA in the brain during the development with in situ hybridization. The immunohistochemical results revealed co-localization of HA and 5-HT within a subgroup of cells in the developing raphe nuclei between E14 and E18. From E18 onwards HA immunoreactivity started to gradually disappear from the rhombencephalon, and was totally abolished by E20, while 5-HT-ir cells continued to establish their adult positions. No significant colocalization of HA and TH immunoreactivities was detected. The biochemical results were in agreement with the immunohistochemical ones and confirmed that histamine detected in the early developing brain is authentic. A positive in situ hybridization signal for HDC was detected in a small area in the ventrolateral pons in the same areas as HA- and HDC-ir cell bodies at E16, suggesting that at least some HA may be synthesized locally. These results confirm that HA is one of the first neurotransmitters to appear in the developing brain. In addition, the transient co-localization of HA and 5-HT immunoreactivities and the transient HDC expression at E16 within the developing pontine raphe nuclei may imply an interesting and a more general role for HA in modification of brain development. PMID- 7798376 TI - Distribution of corticospinal motor neurons in the postnatal rat: quantitative evidence for massive collateral elimination and modest cell death. AB - The postnatal development of rat corticospinal motor neurons (CSMN) was studied by retrograde tracing with cholera toxin B subunit (CTB) injected into the upper cervical dorsal spinal cord on the first postnatal day (P0), P3, P10, P20, and at adulthood. CTB-labeled neurons were visualized by immunocytochemistry and extensively quantified throughout the cortex. At P0, CSMN were found to an extent similar to that reported in P3 animals with other neuronal tracers, now permitting in vitro studies of neonatal CSMN. Between P0 and P3, the number of labeled neurons increased by 30% to a total maximum of approximately 185,000 in both cortices. The increase occurred throughout the cortex. At P10, the number of labeled CSMN had decreased to 60% of the number at P3. Fewer CSMN were evident particularly in the perirhinal cortex. Between P10 and P20, the number of CSMN decreased further to 52% of the maximal number at P3. This decrease occurred predominantly in the cingulate and parietal cortex. The number of labeled CSMN in rats injected at P0 and analyzed at P20 was 10% lower than the number in P0 injected littermates that were analyzed at P3, which suggests that only a small portion of the "disappearing" CSMN undergoes developmental neuronal death. Thus, the spinal projection of the remaining 38% is apparently eliminated between P3 and P20. Detailed quantitative analysis of the CSMN distribution demonstrated that neuronal death occurs predominantly in the perirhinal cortex. In contrast, axonal elimination of corticospinal projections occurred throughout the CSMN field, i.e., primarily in the frontal, occipital, and perirhinal cortex between P3-P10 and in the cingulate and parietal cortex between P10-P20. PMID- 7798377 TI - A reticuloreticular commissural pathway in the rat thalamus. AB - To further characterize the communication between the thalami of the two hemispheres, a connection linking the rostral reticular nuclei of the two thalamic sides was investigated in the rat by retrograde and anterograde tracing. The rostral reticular nucleus can be divided into a medial region, with densely packed fusiform neurons, and a lateral region, with less densely packed, polymorphic neurons. After injections of Fluorogold (FG) in the medial region, retrogradely labeled, small fusiform neurons were found in the corresponding contralateral region. The retrograde labeling data were confirmed by the anterograde-tracing experiments. Thin, beaded axons, anterogradely labeled after injection of biocytin or biotinylated dextranamine in the medial region, innervate the corresponding region in the contralateral reticular nucleus. The present data suggest the existence of a commissural pathway specifically devoted to the crosstalk between the rostral reticular nuclei of the two thalamic sides. The commissural gamma aminobutyric acid (GABA)-ergic input on the GABAergic neurons of the rostral reticular nucleus could modulate the generation of sleep spindles. The reticuloreticular pathway may, moreover, synchronize the diffuse modulatory effect of the rostral reticular nucleus on nonprimary cortical areas through the bilateral projections of the nucleus to the ventromedial, intralaminar, and anterior thalamic nuclei. PMID- 7798378 TI - Cone bipolar cells as interneurons in the rod pathway of the rabbit retina. AB - In the mammalian retina, rod signals are transmitted by rod bipolars to the narrow-field, bistratified (AII) amacrine cell. This neuron, in turn, makes gap junctions with the axonal arborization of cone bipolar cells that reside in the vitreal half (sublamina b) of the inner plexiform layer (IPL). After examining rod bipolars and AII amacrines in the rabbit retina, we have now reconstructed from electron micrographs of continuous series of thin sections the synaptic connections of the axonal arborizations of cone bipolar cells that make the highest number of gap junctions with AII amacrines. These axonal arborizations were narrowly confined to stratum 4 (S4) of the IPL and made ribbon synapses to dyads of postsynaptic dendrites that belonged to either ganglion or amacrine cells. In the population of postsynaptic processes, 30% were ganglion cell dendrites. These dendrites were probably originating, at least in part, from on center ganglion cells because their course was confined to sublamina b of the IPL. Of the remaining postsynaptic processes, 51.7% belonged to amacrine cells and 18.3% were not identified. Among the postsynaptic amacrine cell processes, 33.3% returned a reciprocal synapse onto the cone bipolar endings. These reciprocal synapses represented 21.3% of the total input onto the axonal arborizations, the remaining fraction (78.7%) arising from a heterogeneous population of amacrine dendrites that were purely presynaptic to the cone bipolars endings. Pre- and postsynaptic amacrines were part of several distinct microcircuits which suggest complex local processing of both rod and cone signals. Thus, the cone bipolars that make gap junctions with AII amacrines in sublamina b of the rabbit IPL exhibit a substantial output onto ganglion cells. This fact, in conjunction with our previous observations that in this sublamina ganglion cells receive negligible input from rod bipolars and AII amacrines, demonstrates that in the rabbit cone bipolars represent a necessary link in the pathway followed by rod signals to enter on-center ganglion cells. Thus, rod and cone signals ultimately share the same integrating mechanisms and converge onto the same set of ganglion cells. PMID- 7798379 TI - Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. AB - Five N-methyl-D-aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we have analyzed the expression patterns of mRNAs for the NMDA receptor subunits in the developing and adult rats by in situ hybridization. The developmental changes of the expression patterns were most salient in the cerebellum. In the external granular layer, hybridization signals of mRNAs for NR1, NR2A, NR2B, and NR2C appeared by postnatal day 3, but no NR2D mRNA was expressed at any developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stages examined. The signals for the NR2A mRNA appeared in Purkinje cells and granule cells during the second postnatal week. The signals for the NR2B mRNA in granule cells were seen transiently during the first 2 weeks after birth. The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week. The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells. In the cerebellar nuclei, mRNAs for NR1, NR2A, NR2B, and NR2D were more or less expressed on postnatal day 0, while expression signals for the NR2C mRNA were first detected in postnatal day 14. Thus, the most conspicuous changes of expression patterns were observed in the cerebellar cortex during the first 2 weeks after birth, when development and maturation of the cerebellum proceed most rapidly. PMID- 7798380 TI - Distribution of motoneurons supplying dorsal and ventral suboccipital muscles in the feline neck. AB - A combination of retrograde tracers was used to compare the relative distributions of motoneurons supplying the ventral and lateral suboccipital muscles, rectus capitis anterior (RCA), and rectus capitis lateralis (RCL), with those supplying dorsal muscles, including rectus capitis posterior muscles (RCP), complexus (CM), and the medial head of obliquus capitis superior (OCS). Three of the tracers, horseradish peroxidase, fluororuby, and fluorescein-conjugated dextran, were applied to cut nerve ends. Fast blue was applied by intramuscular injection, and fluorogold was delivered both by injection and by cut nerve exposure. Motoneurons supplying RCA and RCL were clustered on the medial wall of the ventral horn in a restricted region defined previously as the commissural nucleus. Labelled cells supplying RCL were confined to the C1 segment, but those supplying RCA were distributed from C1 to rostral C4. Motoneurons supplying RCA tended to lie more dorsomedially than those supplying RCL, but there was substantial overlap between the two populations. Motoneurons supplying dorsal muscles had a separate, more ventral distribution. RCP motoneurons were located primarily in the ventromedial nucleus, but a small proportion of cells was found in the white matter of the ventral funiculus or the gray matter surrounding the central canal. Motoneurons supplying CM and OCS were located dorsomedially to the RCP cell population. These results suggest that neck motoneurons are arranged according to a "musculotopic" pattern in which dorsal muscles have the most ventral locations, and progressively more lateral and then ventral muscles are layered dorsomedially along the medial wall of the ventral horn. PMID- 7798381 TI - Ontogeny and effect of activity on proenkephalin mRNA expression during development of the chick spinal cord. AB - Numerous studies have shown in the adult nervous system that mRNA expression can be regulated by neuronal activity. To examine the effect of activity during embryogenesis, the ontogeny of proenkephalin mRNA expression and expression following activity blockade was investigated during development of chick spinal cord. A cDNA fragment (ca. 0.5 kb) coding for chick proenkephalin was cloned and sequenced. With this cDNA, a cRNA probe was made to examine proenkephalin mRNA expression in the spinal cord during embryogenesis. Proenkephalin mRNA was expressed in spinal cord in clusters of cells located in the developing dorsal horn and intermediate lamina at the earliest stages examined (stage 22; E4). Proenkephalin-positive cells in the intermediate lamina were located immediately adjacent to the ventricular zone. At stage 28 (E6) an additional cluster of proenkephalin mRNA-positive cells was seen at the lateral border of the developing intermediate lamina. At stage 33 (E7.5-5-8) the pattern of hybridization positive cells was similar to earlier stages, but individual cells could be identified. At stage 39 (E13) densely labeled cells were seen throughout the dorsal horn and intermediate laminae including the column of Terni. To determine whether neural activity affects proenkephalin mRNA expression, d tubocurarine (an inhibitor of neural activity) was injected into developing embryos. Following administration of d-tubocurarine a dramatic decrease was seen in proenkephalin mRNA hybridization in the dorsal horn and intermediate lamina of the spinal cord. This study demonstrates in vivo that changes in the level of neural activity can alter gene expression during embryogenesis and suggests that activity is required for expression of nervous system-specific genes. PMID- 7798382 TI - Brainstem network controlling descending drive to phrenic motoneurons in rat. AB - Contraction of the diaphragm is controlled by phrenic motoneurons that receive input from sources that are not fully established. Bulbospinal (second-order) neurons projecting to phrenic motoneurons and propriobulbar (third-order) neurons projecting to these bulbspinal neurons were investigated in rat by transsynaptic transport of the neuroinvasive pseudorabies virus. Bulbospinal neurons were located predominantly in the medullary lateral tegmental field in two functionally described regions, the ventral respiratory group and Botzinger complex. An intervening region, the pre-Botzinger complex, contained essentially no phrenic premotoneurons. Bulbospinal neurons were also located in ventral, interstitial, and ventrolateral subnuclei of the solitary tract, and gigantocellular, Kolliker-Fuse, parabrachial, and medullary raphe nuclei. A monosynaptic pathway to phrenic motoneurons from the nucleus of the solitary tract was confirmed; monosynaptic pathways from upper cervical spinal cord, spinal trigeminal nucleus, medical and lateral vestibular nuclei, and medial pontine tegmentum were not verified. Locations of third-order neurons were consistent with described projections to the ventral respiratory group, from contralateral ventral respiratory group, Botzinger complex, A5 noradrenergic cell group, and the following nuclei; solitary, raphe, Kolliker-Fuse, parabrachial, retrotrapezoid, and paragigantocellular. Novel findings included a projection from locus coeruleus to respiratory premotoneurons and the lack of previously described pathways from area postrema and spinal trigeminal nucleus. These second and third-order neurons from the output network for diphragm motor control which includes numerous behaviors (e.g., respiration, phonation, defecation). Of the premotoneurons, the rostral ventral respiratory group is the primary population controlling phrenic motoneurons. PMID- 7798383 TI - Morphological maturation of thalamic neurons as studied in fetal neural transplants. AB - This study attempts to determine whether fetal thalamic neuroblasts from rat embryos (embryonic age 15 days) labeled with horseradish peroxidase (HRP) can differentiate into their normal dendritic phenotype when transplanted as a cell suspension into a lesioned site in the adult somatosensory thalamus. The HRP labeling provided a Golgi-like staining of numerous neurons up to 12-14 days after transplantation. There were three main results. 1) As early as 2 days after transplantation three morphologic cell types were observed: Two were bipolar and the third multipolar. These cellular profiles are characteristic of adult ventroposterolateral, reticular, and ventroposteromedial neurons and suggest that transplanted neurons can take shape in the absence of specific arrangements of afferent fibers. 2) The initial stage of dendritic growth was characterized by numerous growing specializations and consisted of a rapid, arborizing growth that appeared to proceed at an accelerated rate relative to normal development. During the later stage, which was characterized by the great reduction of growing specializations, dendritic remodeling resulted in a simpler morphology, and the transplanted neurons did not achieve an adult morphology. 3) Putative axons exhibiting growth cones were present in impressive densities in the transplants, and a number of them grew into the neuron-depleted host thalamus. A very small number of axons grew into host gray matter outside the lesioned area, indicating that neurodegenerative areas provide a better substrate for neurite outgrowth than intact tissue. In rare instances axons were visible in the internal capsule, indicating that the biochemical inhibition provided by mature myelin and oligodendrocytes may not be an absolute obstacle to axonal growth. PMID- 7798384 TI - Idiopathic plantar hidradenitis: a neutrophilic eccrine hidradenitis occurring primarily in children. AB - Neutrophilic eccrine hidradenitis (NEH) has been described in a variety of clinical settings but is most often seen in leukemic patients receiving chemotherapy. We have recently encountered 6 healthy individuals, of whom 5 were children, who developed NEH localized to the feet. The patients were from 9 to 21 years of age. The presenting complaint was rapid development of tenderness of the feet with varying degrees of morbidity. At clinical evaluation, tender, erythematous papules and nodules were confined to the feet, primarily the plantar surfaces. The major differential diagnoses were erythema nodosum and vasculitis. Laboratory studies were non-contributory. Histologically, the findings were generally similar to those of NEH with certain exceptions, most notably the absence of syringosquamous metaplasia and the presence, in most cases, of neutrophilic abscesses in eccrine coils. Inflammatory and degenerative changes involved primarily the eccrine duct (coiled and dermal), and tended to spare the secretory apparatus. Stains for microorganisms were negative. There were brief recurrences in some of the patients, but those followed over time have remained well. We suggest the term idiopathic plantar hidradenitis for this condition. PMID- 7798385 TI - Melanocytes in human skin express bcl-2 protein. AB - The bcl-2 gene was initially identified through its participation in the translocation 14:18 in B-cell lymphomas of follicular center cell origin. This classic translocation juxtaposes the transcriptionally active immunoglobulin heavy-chain locus on chromosome 14 to the bcl-2 gene on chromosome 18, resulting in overexpression of bcl-2 protein. The oncogene bcl-2 is thought to prolong cell survival through interference with programmed cell death. To date, bcl-2 expression has been reported in normal lymphoid, hemopoietic, neural, breast and prostatic tissues. Since melanocytes are neural crest derivatives and have an extended life-span, our objective was to determine whether the bcl-2 protein is expressed in human melanocytes. We analyzed normal skin biopsies for bcl-2 expression using standard immunohistochemistry. As hypothesized, dendritic cells in the basal epidermal layer stained strongly for bcl-2. The distribution and morphology of these cells was typical for melanocytes. Additionally, eccrine sweat glands, lymphocytes and the dermal papilla of hair follicles demonstrated bcl-2 positivity. We believe this to be the first report of bcl-2 expression in normal melanocytes. PMID- 7798386 TI - Characterization of the mononuclear infiltrate involved in regression of halo nevi. AB - Halo nevi are characterized by progressive degeneration of nevus cells surrounded by a mononuclear cell infiltrate. We studied the morphological features of the nevus cells and the composition of the mononuclear cell infiltrate in 15 cases of halo nevi using immunohistochemical techniques and a battery of antibodies to different subsets of lymphocytes and histiocytes. Regression could be divided into four more or less identifiable stages, associated with different subsets of lymphocytes and monocyte-macrophage lineage cells. Stage I (preregression): nests of unremarkable nevus cells were surrounded by a moderate number of T lymphocytes (relatively small percentage of helper inducer T cells), occasional B cells and macrophages. Stage II (early regression): large number of T lymphocytes and FXIIIa-positive cells were in close contact with nevus cell clusters which showed ragged edges. Lysozyme-positive cells and epidermal Langerhans cells were mildly increased. Stage III (late regression): single nevomelanocytes showing mild atypia were present. Numerous T lymphocytes and macrophages positive for lysozyme, KP1 and/or FXIIIa were interspersed between the nevus cells. Increased numbers of epidermal Langerhans cells were present. Stage IV (complete regression): no nevus cells were observed and moderate numbers of T lymphocytes only remained. These results suggest that T cells, especially T-suppressor cells, and different subsets of macrophages participate in the regression of the nevi. PMID- 7798387 TI - Pseudoepitheliomatous hyperplasia in chronic cutaneous wounds. A flow cytometric study. AB - Cutaneous squamous cell carcinomas (SCC) arising in a setting of chronic regeneration and repair tend to be highly aggressive lesions prognostically distinct from SCC arising in solar-damaged skin. Full thickness thermal injury and chronic nonhealing ulcers are predisposing conditions in up to 2% of SCC. A significant association has been suggested to exist between pseudoepitheliomatous hyperplasia (PH) and SCC. Three-hundred-eighty-six surgical cases of skin excised secondary to severe burns (n = 254) or chronic ulcers (n = 132) were reviewed, yielding 43 (11%) with PH. Flow cytometric DNA analysis was performed on paraffin embedded sections. Thirty cases without PH were studied in addition to the 43 cases with PH. The majority (39/43) of the PH cases showed a single diploid population with a mean S-phase of 13.7%. Four cases (9.3%) showed an aneuploid peak. All cases without PH were diploid with a mean S-phase of 9.0%. In this study, PH was present in 11% of cases reviewed, and showed a 50% mean higher S phase than comparable cases without PH. Aneuploidy was present in 9.3% of the PH cases studied. SCC may arise from a subgroup of PH in a background of rapidly proliferating keratinocytes. PMID- 7798388 TI - Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus. AB - Aberrant p53 immunoreactivity has been found in skin pre-malignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on formalin-fixed and paraffin embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 +/- 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 +/- 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 +/- 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 +/- 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798389 TI - Techniques in immuno-electron microscopy. I. Cryosubstitution. AB - Normal skin was cryoprotected by submerging it in a mixture of 30% dimethylformamide (DMF) in PBS or RPMI. Subsequently it was frozen in liquid propane gas. Cryosubstitution was carried out at -90 degrees C by using methanol to which uranyl acetate or osmium tetroxide were added. The tissue was embedded in either Lowicryl K4M at -40 degrees C or in Epon at +60 degrees C. The tissue was evaluated by its overall preservation of ultrastructural details and by its labeling intensity after incubation with either anti-desmoglein or anti-type VII collagen monoclonal antibodies. The mixture of DMF and PBS caused an electron dense precipitate within the cell. The overall morphology was better in Epon embedded material than in K4M-embedded material. However, the labeling was best in K4M material. Regardless of whether the tissue was embedded in Epon or K4M, the addition of osmium tetroxide markedly reduced the degree of labeling. PMID- 7798390 TI - DNA determination of human hair bulbs in normal and androgenetic alopecia. AB - We carried out a cytophotometric study of the DNA content of matrix cells from normal hair follicles and those affected by androgenetic alopecia (early and established baldness), using the Feulgen technique. We thereby obtained a 2C reference value from lymphocyte nuclei from normal skin, from which we established a 2C-4C and 4C DNA content. The results obtained showed 71.75% of matrix cells in normal scalp to have a 2C content, while the remaining 28.25% was distributed between the values of 2C-4C and 4C. However, in early baldness, the number of 2C cells dropped to 48%, with a notable increase in cell populations with a 2C-4C and 4C content, which varied from 29.45% and 22.55% respectively. Finally, in established baldness, the 2C values decreased to as low as 29.56%, with the percentage of cells with a 2C-4C content reaching 38.71% and those of 4C, 31.73%. PMID- 7798391 TI - Arteriovenous hemangioma: a clinicopathological and immunohistochemical study. AB - The clinicopathological and immunohistochemical properties of 6 examples of arteriovenous hemangioma, including 2 intraoral lesions, were reviewed. This distinct benign, acquired vascular lesion, infrequently encountered in the literature, is characterized by multiple thick- and thin-walled vascular spaces resembling arteries and veins, respectively. In our study, we performed elastic stains that revealed a prominent venular component, whereas the arterial aspect was inconspicuous to absent. Our aim was also to elucidate the possible histogenesis of this lesion. Previous reports suggest as pathogenetic mechanisms hamartomatous proliferation either of the subpapillary vascular plexus or of the Suquet-Hoyer canal of the true glomus. Our immunohistochemical studies failed to identify typical glomus cells. In addition, we investigated the mast cell count in all lesions and it was found increased. These findings, as well as recent evidence directly implicating mast cells in angiogenesis, can support the theory of hamartomatous proliferation of the subpapillary plexus. One should also not exclude the possibility of a reactive process resulting in the characteristic features of arteriovenous hemangioma. PMID- 7798392 TI - Eruptive xanthomata with urate-like crystals. AB - The microscopic manifestations of eruptive xanthomata are variable and although they are most frequently characterized by aggregations of foamy macrophages in the dermis, they can, on occasion, simulate granuloma annulare. We have recently encountered a further unusual histopathological variant of eruptive xanthomata in 3 skin biopsies from 2 patients with hypertriglyceridemia. The lesions had a granuloma annulare-like pattern at low magnification, the exceptional feature being their content of polarizable, needle-shaped crystals. These bore a strong resemblance to monosodium urate monohydrate and displayed negative birefringence under polarized light. In the case of each patient, an initial pathological diagnosis of gout was rendered, and the true nature of the lesions came to light only after clinicopathologic correlation. While it is clear that the chemical composition of these crystals requires further study, recognition of this microscopic variant of eruptive xanthomata should help to reduce errors in diagnosis. PMID- 7798393 TI - Low-grade fibromyxoid sarcoma: case report and immunohistochemical study. AB - A case is presented of low-grade fibromyxoid sarcoma involving the arm of a 52 year-old man. Low-grade fibromyxoid sarcoma is a recently described neoplasm of the deep and subcutaneous soft tissue which demonstrates a spectrum of histologic images. The current case demonstrated the typical patterns of intermixed, sweeping bands of fibrous and myxoid tissue, homogeneous foci of fibrous and myxoid tissue, focal areas of storiforming, and concentric perivascular cuffs of slender spindle cells, all lacking the nuclear anaplasia, mitotic activity, and necrosis generally associated with sarcoma. Immunohistochemical analysis performed on paraffin-embedded sections demonstrated strong labeling of the tumor cells by anti-CD34 antibody, moderate labeling for vimentin, and rare, focal positivity for muscle-specific actin. Tumor cells were negative for markers of epithelial, muscular, neural, histiocytic, melanocytic, and vascular differentiation. The constellation of histopathologic features described in this and previous reports is characteristic of low-grade fibromyxoid sarcoma. Based on this case, it appears that the immunohistochemical features of low-grade fibromyxoid sarcoma can help to exclude many cutaneous and deep soft tissue tumors from the differential diagnosis. The findings support the interpretation that the neoplasm is essentially fibroblastic in nature. PMID- 7798394 TI - Diffuse dermal angiomatosis: a variant of reactive cutaneous angioendotheliomatosis. AB - Reactive angioendotheliomatosis (RA) is a rare, benign disease. Affected patients present with self-limited, erythematous to violaceous plaques. The clinical lesions are due to intravascular hyperplasia of cytologically banal endothelial cells in the dermis. We report 2 patients who presented with ulcerated, violaceous plaques on the lower extremities. Both had severe peripheral vascular atherosclerotic disease requiring bypass grafts. Unlike previously described cases of RA, our patient's lesions were due to a diffuse proliferation of endothelial cells in the reticular dermis with only minimal, focal intravascular proliferation of these cells. Positive immunostaining with antibodies to Factor VIII-related and CD34 antigens adds evidence that the proliferated cells in the dermis were endothelial cells. PMID- 7798395 TI - Dermatomyofibroma: report of two cases. AB - Dermatomyofibroma is a recently described, benign acquired cutaneous proliferation of fibroblasts and myofibroblasts. We report 2 additional cases, both in young women. The lesions measured 0.5 and 1.0 cm and were located on the breast and upper back. Follow-up at 8 months and 3 years revealed no evidence of recurrence. Both lesions exhibited a uniform population of spindle cells forming intersecting long fascicles with a tendency to horizontal orientation in the reticular dermis. Cytologic atypia was absent and mitotic figures were minimal or absent. Collagen was present as thin fibers separating individual cells and as thicker bundles between the fascicles. A fine reticulin network surrounded the spindle cells. Elastic fibers were mostly preserved and appeared thicker or even increased in number. The spindle cells were immunoreactive for vimentin and muscle actin and negative for desmin, S-100 protein, factor XIIIa, and CD34. Electron microscopic studies confirmed the presence of myofibroblasts. The differential diagnosis was made with cellular and fibrous dermatofibroma, piloleiomyoma, hypertrophic scar, and dermatofibrosarcoma protuberans, both classic and plaque type. The data presented supports the histologic distinction of dermatomyofibroma from other fibroblastic proliferations of the skin. PMID- 7798396 TI - Cutaneous Rosai-Dorfman disease presenting as a suspicious breast mass. AB - Cutaneous Rosai-Dorfman disease in a male patient presented as a clinically malignant left breast mass. The intra-operative frozen section indicated a benign inflammatory lesion and a simple excision was performed. The disease was apparently limited to the skin and subcutis of the left breast with no lymph nodes or other organs involvement. While the lesion demonstrated the characteristic morphology of Rosai-Dorfman disease, the diagnosis of granulomatous mastitis, epithelioid sarcoma and other cutaneous xanthohistiocytic proliferations were considered. In the absence of lymphadenopathy, a high index of diagnostic awareness is required to recognize the uncommon, solitary cutaneous Rosai-Dorfman disease. PMID- 7798397 TI - Designing preclinical instruction for psychomotor skills (I)--theoretical foundations of motor skill performance and their applications to dental education. PMID- 7798398 TI - Designing preclinical instruction for psychomotor skills (II)--instructional engineering: task analysis. PMID- 7798399 TI - The International Cochrane Collaboration Oral Health Group--making the results of controlled trials properly accessible. PMID- 7798400 TI - Dental school teaching clinics as cost centers. AB - Increasing net patient revenues from teaching clinics is one of the alternatives available to dental schools seeking to alleviate economic pressures. Managerial decisions directed to this end require accurate and useful data on clinic finances and economic organization. An important step in this direction can be taken by defining the teaching clinic as a cost center, that is as an economic entity in a dental school with identifiable specific resources, costs, and revenues. This paper describes the accounting and economics frameworks within which resources and costs are classified and allocated into direct and indirect, and fixed and variable categories. The development and structure of a cost revenue model designed for the teaching clinics at the University of Connecticut School of Dental Medicine is described to illustrate an application of the cost center concept. PMID- 7798401 TI - An application: the cost of clinic care by undergraduate dental students and its relationship to clinic fees. PMID- 7798402 TI - Outcomes assessment of a predoctoral research program. PMID- 7798403 TI - Responsibilities of faculty managers in predoctoral general practice programs. PMID- 7798404 TI - An application of team learning in dental education. PMID- 7798406 TI - The future of dental education. PMID- 7798405 TI - PENN PASS: a program for graduates of foreign dental schools. AB - An increasing number of graduates of foreign dental schools who enroll in advanced standing programs to qualify for licensure calls for dental schools to be prepared to handle not only the curricular demands but also the growing cultural diversity among its student population. The "reeducation" of this student group not only meets the need of foreign dentists for an American degree but may also provide health professionals to service various ethnic populations whose language and culture they are able to understand and identify with. A survey of students and graduates of a two-year Program for Advanced Standing Students (PASS) for graduates of foreign dental schools representing 34 countries aimed to arrive at an understanding of this student group through characterization of the foreign dentists and identification of their attitudes and feelings toward various aspects of the program, the school and faculty and their experience of stress. This report includes description of the distinctive features of the program which cater to specific needs and concerns of this non traditional group of dental students. PASS students are accepted on the basis of their grades in dental school in home country, scores in the National Dental Board Examination Part I, Test of English as Foreign Language (TOEFL), and ratings in personal interviews. They complete an intensive summer program consisting of didactic and laboratory courses which prepares them for integration with four-year students for the last two years of didactic and clinical curriculum. Cultural diversity seminars, a special English class, PASS class meetings and seminars are unique additions to their program and aim to assist them adjust to the educational, social and cultural systems in an American school. Results of the survey show a majority of the PASS students feel that they are part of the school and that there is someone in the school whom they can approach for problems. An understanding of their ethnic and educational background is seen as a significant factor in their second basic dental education. Implications for education of foreign dental graduates amidst increasing diversification of the student body are discussed. PMID- 7798407 TI - Dermabrasion. Taking the frost off the fraise. PMID- 7798408 TI - Stump the experts. Eccrine acrospiroma. PMID- 7798409 TI - Elliptical donor stereoscopically assisted micrografting as an approach to further refinement in hair transplantation. AB - BACKGROUND: Multiple surgical methods are currently used for hair transplantation. Each method has a specific technique, morbidity, and relatively predictable cosmetic result. OBJECTIVE: To describe a methodology that combines elliptical excision of donor tissue and dissection under stereoscopic magnification into small grafts to obtain an improved final cosmetic result. For the purposes of this paper, any graft small enough to be easily inserted into a 16-, 18-, or 20-gauge needle tunnel will be referred to as a micrograft. METHOD: Three hundred thirty patients underwent transplantation by this method over a 6 year period. All patients were photographed before, during, and upon completion to monitor results. RESULTS: Cosmetic results as documented by examination and photography represent a further refinement due to the large number and small size of grafts placed. CONCLUSION: The author considers the method described as a viable alternative technique in hair transplantation for both limited and extensive androgenetic alopecia. PMID- 7798410 TI - The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser. A comparative study. AB - BACKGROUND: The Q-switched ruby laser (QSRL) (694 nm) has been used successfully in the removal of tattoos and a variety of cutaneous pigmented lesions. The frequency-doubled Q-switched neodymium:yttrium-aluminum-garnet laser (QSNd:YAG) (1064 and 532 nm) has also been shown to be effective in the treatment of tattoos, however, little has been published regarding the QSNd:YAG laser in the removal of cutaneous pigmented lesions. OBJECTIVE: The purpose of this study is to compare the efficacy and side effect profile of the QSRL and the frequency doubled QSNd:YAG lasers in the removal of cutaneous pigmented lesions, including lentigines, cafe-au-lait macules, nevus of Ota, nevus spilus, Becker's nevus, postinflammatory hyperpigmentation, and melasma. METHODS: Twenty patients with pigmented lesions were treated with the QSRL and the frequency-doubled QSNd:YAG lasers. Clinical lightening of the lesion was assessed 1 month after a single treatment. Side effects and patient satisfaction were also evaluated. RESULTS: A minimum of 30% lightening was achieved in all patients after only one treatment with either the QSRL or the frequency-doubled QSNd:YAG laser. The QSRL seems to provide a slightly better treatment response than the QSNd:YAG laser. Neither laser caused scarring or textural change of the skin. Most patients found the QSRL to be more painful during treatment, but the QSNd:YAG laser caused more postoperative discomfort. CONCLUSION: Both the QSRL and the frequency-doubled QSND:YAG laser are safe and effective methods of treatment of epidermal and dermal pigmented lesions. PMID- 7798411 TI - Dermabrasion using tumescent anesthesia. AB - BACKGROUND: Dermabrasion is a very useful and versatile technique. However, it suffers from side effects and difficulties that limit its popularity among operating dermatologic surgeons and the public. OBJECTIVE: To show that it is possible to eliminate the need for chlorofluorocarbons, improve the standard dermabrasion technique, decrease the healing time, improve its side effect profile, and reduce risks to the operating surgeon. METHODS: Tumescent fluid containing dilute Xylocaine, bicarbonate, and epinephrine in saline was infiltrated before coarse wire brush dermabrasion. Eutectic mixture of local anesthetic (EMLA) was also used topically. The first 14 patients dermabraded by this method are reported on here. Their healing, progress, side effects, and results are described. A patient questionnaire was completed by 12 of the patients who describe the procedure and results from the patient's viewpoint. RESULTS: The procedure was found to be effective in producing anesthesia, eliminating the use of freezing the skin, and limiting the necessity for sedatives, narcotics, and other anesthesia. It gives a firm surface to dermabrade against, makes the procedure more rapid and technically easier, and produces less splatter and therefore less risk for the surgeon. The results subjectively and objectively would appear to be at least as good as standard techniques. The healing in this small sample would appear to be faster both to reepithelialization and to reestablishment of normal color. There was only one case of transient hyperpigmentation lasting less than 1 week. Otherwise there were no cases of pigmentary or scarring side effects. CONCLUSION: Tumescent dermabrasion is safe, effective, and has many benefits over traditional methods. PMID- 7798412 TI - CO2, argon, and pulsed dye laser treatment of angiofibromas. AB - BACKGROUND: Tuberous sclerosis is a complex disorder of hamartoma formation in many organs, particularly the skin, brain, eye, kidney, and heart. The characteristic skin lesions are angiofibromas (AF), the shagreen patch, periungual fibromas, and "ash-leaf" white macules. Treatment for AF has previously included electrocoagulation, electrodesiccation and curettage, dermabrasion, excision, cryosurgery, and oral 13-cis retinoic acid. Both argon and CO2 lasers have been used in isolated cases to treat AF. OBJECTIVE: The purpose of this work is the study of the application of three different lasers in the treatment of facial AF. METHODS: Ten patients with facial AF were treated with CO2, argon, and pulsed dye lasers. Patients' AF were graded with regard to the size and color of the lesions. A 2-3-cm2 test was assayed on the face of all patients with each laser before performing a complete treatment and in order to choose the best laser. RESULTS: Results were considered excellent in seven patients and good in three patients, with decrease of erythema and flattening of the AF. Minimal scarring was noted in two patients. Transient erythema was observed in patients treated with the CO2 laser. All patients or their parents considered the treatment cosmetically satisfactory. CONCLUSION: We found the CO2 laser to be a better therapeutic tool than the argon laser to treat AF, especially in those patients with multiple and protuberant AF. The argon laser would be more useful in those patients with very red AF and light complexion, and the pulsed dye laser in those with very red and flat AF. PMID- 7798413 TI - Standardizing chemical peel solution formulations to avoid mishaps. Great fluctuations in actual concentrations of trichloroacetic acid. AB - BACKGROUND: Chemical peeling using trichloroacetic acid (TCA) is a popular and long utilized procedure in dermatology and cosmetic surgery. OBJECTIVE: To determine the actual concentration of TCA in four disparate methods of preparation of solutions, expressed in the standard pharmaceutical method of weight to volume (wt/vol). METHODS: Method I was wt/vol, method II was weight to weight (wt/wt), method III was grams of TCA added to 100 cc water, and method IV was the usage of saturated TCA, and calling it 100%, then making appropriate dilutions. The amounts of TCA in each solution for methods II, III, and IV were converted, by calculation, to the wt/vol method. RESULTS: The relative concentrations of TCA, ranked by the wt/vol pharmaceutical standard, showed that from strongest to weakest: method IV > method II > method I > method III. CONCLUSIONS: Tremendous variations were found in the relative concentrations of TCA in these solutions. To avoid mishaps and complications, the wt/vol method should be used. PMID- 7798414 TI - Acral lentiginous melanoma. A histological type without prognostic significance. AB - BACKGROUND: Acral lentiginous melanoma (ALM) is reported to have a poorer prognosis than melanomas of other histotypes. OBJECTIVE: The purpose of this paper is to verify if ALMs, per se, have a more aggressive behavior or if the poorer prognosis of these patients is due to a later diagnosis. METHODS: Clinical charts of 165 patients with acrally located melanoma were reviewed as well as all histological slides. In all patients, histotype, Clark's level, Breslow thickness, pigmentation, presence of ulceration, and regression were reported. Mitotic index, vascular invasion, and microscopic satellitosis were also determined. Survival of the 64 patients with ALM was compared with survival observed in the remaining 101 acral (nonlentiginous) melanomas. RESULTS: Melanoma localized at acral sites constitute 8.9% of the 1845 patients with melanoma treated at our Institute from 1975 to 1990. All were Caucasian, 57 were males, and 108 females. Out of the 165 patients with this localization, 64 (38.8%) were classified as ALM. Disease-free and overall survival of the 64 ALM patients were not different at a statistically significant level compared with the areas observed in the other acral nonlentiginous melanoma. CONCLUSION: The survival difference between ALM and other histological types is due to a later diagnosis and not to a more aggressive behavior of ALM. PMID- 7798415 TI - Oral transmucosal fentanyl citrate premedication in patients undergoing outpatient dermatologic procedures. AB - BACKGROUND: Oral transmucosal fentanyl citrate (OTFC) is a novel lozenge dosage form of fentanyl used for premedication. Many dermatology patients undergoing surgical procedures could benefit from such a medication. OBJECTIVE: The study compared the safety and efficacy of 400-vs 800-micrograms dosage forms for their sedative and anxiolytic effects in adults undergoing a variety of dermatologic outpatient surgical procedures. METHODS: Patients received OTFC 30 minutes before the procedure. Vital signs, oxygen saturation, sedation, and anxiety scores were measured before OTFC administration and every 15 minutes thereafter. RESULTS: Significant sedation and anxiolysis developed in both dosage groups. No clinically significant changes in respiratory rate, heart rate, or blood pressure occurred during the study period. Common drug-induced side effects included dizziness, nausea, pruritus, and vomiting. CONCLUSION: OTFC is safe and effective for outpatient dermatologic procedures; however, the risk of opioid-related side effects must be carefully weighed against the benefits when deciding to use OTFC in an outpatient setting. PMID- 7798416 TI - Split skin grafting on severely damaged skin. A technique using absorbable tissue adhesive. AB - BACKGROUND: Patients with severely damaged skin are more likely to develop skin malignancies. However, suturing following excision of tumors is difficult due to their fragile skin. OBJECTIVE: To evaluate the effectiveness of a technique using butyl-2-cyanoacrylate tissue adhesive in split skin grafts in patients with severely damaged skin. METHOD: The technique was used in 19 patients with 24 skin tumors. Two patients also had multiple skin biopsies to assess the biodegradability of the adhesive. RESULTS: Split skin grafts were applied successfully in all patients. The adhesive was completely absorbed without a foreign body reaction within 6 months. CONCLUSION: We recommend the use of butyl 2-cyanoacrylate in split skin grafting patients with severely damaged skin. PMID- 7798417 TI - Q-switched ruby laser treatment of labial lentigines in Peutz-Jeghers syndrome. AB - BACKGROUND. The Q-switched ruby laser emits energy with a 694-nm wavelength and has a pulse duration in the nanosecond range, which allows selective treatment of benign pigmented lesions. Labial and perioral pigmented macules associated with Peutz-Jeghers syndrome are often numerous and cosmetically disfiguring. RESULTS/CONCLUSION. We report successful treatment of these lentigines with the Q switched ruby laser and consider it the treatment of choice for these lesions. PMID- 7798418 TI - Treatment of pyoderma gangrenosum with cultured keratinocyte autografts. AB - BACKGROUND: Pyoderma gangrenosum is an uncommon chronic skin disease characterized by rapidly enlarging cutaneous ulcers. Immunosuppressive agents, such as corticosteroids, are the mainstay of therapy. OBJECTIVE: We describe a patient with pyoderma gangrenosum treated with cultured keratinocyte autografts for a full-thickness ulcer located on the dorsal and lateral aspects of the foot. METHODS: After stabilizing the ulcer with intralesional and systemic corticosteroids, the ulcer was debrided and cultured keratinocyte autografts were secured with nylon mesh. An outer dressing of gauze and elastic bandage was used. RESULTS: The patient had > 95% "take" of the grafts and the ulcer was fully healed in less than 1 month. The grafted area preserved the clinical phenotype of the palmar skin from which the original biopsy was taken. CONCLUSION: Cultured keratinocyte autografts can provide permanent wound coverage for patients on high doses of immunosuppressive medications. PMID- 7798419 TI - Eccrine angiomatous hamartoma. AB - BACKGROUND: Eccrine angiomatous hamartoma (EAH) is a rare benign lesion that mimics a capillary ("strawberry") hemangioma (CH) in appearance. EAH slowly grows and becomes symptomatic whereas CH typically regresses over time. OBJECTIVE: To increase awareness of this rare hamartoma and emphasize the need for histopathologic evaluation of similar appearing lesions and thus prompt excision versus observation. METHODS: Literature review and report of an illustrative case. RESULTS: Histopathologic confirmation of EAH in a lesion clinically indistinguishable from CH and successful surgical extirpation. CONCLUSION: EAH is a rare hamartomatous neoplasma clinically similar to CH in appearance. Histopathologic examination of suspected lesions is recommended for delineation as CH generally involutes spontaneously whereas EAH may require surgical excision due to pain and hyperhidrosis. PMID- 7798420 TI - Repair of the soft triangle of the nose. AB - BACKGROUND: Notching of the soft triangle is a complication of excisional and some reconstructive surgery that is difficult to repair. OBJECTIVE: This article provides a simple single-stage procedure to correct the complication of notching of the soft triangle. METHODS: A detailed description of a turnover flap from the inferior tip covered with a full-thickness skin graft is provided. RESULTS: The method described has provided uniformly satisfactorily results based on the author's experience. CONCLUSION: This simple method is the treatment of choice for a one-stage repair of a soft triangle notch. PMID- 7798421 TI - The use of hyaluronidase as an adjunct to surgical procedures. AB - BACKGROUND: Although the use of hyaluronidase as an adjunct to anesthesia is frequently described for plastic surgery and ophthalmologic procedures, its use in dermatologic surgery has not been well investigated. OBJECTIVE: In this report we review the advantages and disadvantages of using hyaluronidase in dermatologic procedures. METHODS: The effect of adding hyaluronidase to local anesthesia was evaluated in 72 operations performed over a 1-year period. RESULTS: Although the duration of anesthesia is slightly decreased, the addition of hyaluronidase to local anesthesia offers the benefits of minimizing loss of surface contour and enhanced ease in undermining and dissection through subcutaneous tissue planes. The onset of anesthesia using hyaluronidase is immediate and the area of anesthesia appears increased over anesthesia without hyaluronidase. CONCLUSION: We therefore recommend the adjunct of hyaluronidase to local anesthesia as a useful advancement in surgical technique. PMID- 7798422 TI - Basal cell carcinoma arising in a surgical scar: reconstructive surgical treatment. PMID- 7798423 TI - Malignant fibrous histiocytoma at the site of total knee replacement. PMID- 7798424 TI - Dohi Memorial Lecture. New therapeutic rewards from clinical research in atopic dermatitis. PMID- 7798425 TI - Detection of human papillomavirus type 60 in plantar cysts and verruca plantaris by the in situ hybridization method using digoxigenin labeled probes. AB - BACKGROUND: Since 1987, many cases have been reported in which human papillomavirus (HPV) could be associated with epidermoid cysts of the palms and soles. In 1989, the HPV found in an induced epidermoid cyst was cloned and named HPV 60. OBJECTIVE: Our purpose was to examine the relationship of HPV 60 to plantar cysts. METHODS: Ten cases of plantar cysts and two cases of verruca plantaris containing single inclusion bodies were obtained by biopsy and examined by the in situ hybridization (ISH) method with a digoxigenin labeled HPV 60 DNA probe. RESULTS: Six of ten cases were found to have cytopathic effect (CPE) in the cyst wall and inner contents of the cyst. HPV 60 was detected in these cases by ISH. Two cases of verruca plantaris showing CPE also demonstrated the presence of HPV 60. Of the six HPV type 60 positive cases, four cases also showed CPE in the overlying epidermis. CONCLUSION: At first, punctate keratotic lesions are induced by HPV 60. HPV 60 induces irregular elongation of the rete ridges into the dermis. Plantar cysts probably form as a result of the traumatic implantation of HPV 60 infected epidermis with irregularly long and narrow rete ridges into the dermis. PMID- 7798426 TI - Interferon-gamma-induced HLA-DR, but not ICAM-1, expression of human keratinocytes is down-regulated by calmodulin antagonist. AB - Interferon-gamma (IFN-gamma) has been shown to induce or enhance the expression of MHC class II and intercellular adhesion molecule-1 (ICAM-1) in a variety of human and murine cell types, including epidermal keratinocytes (KC). However, the expression of MHC class II and ICAM-1 molecules induced by IFN-gamma is not necessarily coordinated. We investigated the inhibitory effects of the calmodulin antagonist, W-7, and its chlorine deficient inactive analogue, W-5, on the expression of MHC class II (HLA-DR) and ICAM-1 by human KC incubated with IFN gamma. We found that the IFN-gamma-induced expression of HLA-DR was reproducibly and dose-dependently inhibited by W-7. However, the expression of ICAM-1 was highly resistant to the inhibitory effects of W-7. Neither HLA-DR nor ICAM-1 expression was affected by W-5. These data suggest that the IFN-gamma-induced HLA DR, but not ICAM-1, expression is mediated, if not exclusively, by calmodulin in human KC. PMID- 7798427 TI - Immunopathologic demonstration of MAC387+ UCHL1+ cells in bullous skin diseases. AB - Immunopathologic aspects of bullous skin diseases were studied in paraffin sections of thirty-three skin biopsy specimens utilizing monoclonal antibodies directed against histiocytes, helper/inducer T lymphocytes, and Langerhans cells in skin lesions. Laboratory examinations revealed that either more or fewer of the standard number of helper/inducer T lymphocytes (UCHL1+) were observed in the upper dermis in 84.8% of the cases examined, particularly in the various forms of pemphigus; histiocytes (MAC387+) were also found to occur in the upper dermis in 45.5% of the cases and blisters in 27.3% of the cases, particularly in pemphigus erythematosus and dermatitis herpetifomis. In 54.5% of all the cases, both UCHL1+ and MAC387+ cell infiltrates predominated in the upper dermis. These findings suggest that a cell-mediated immune response may also be important in the pathogenesis of bullous skin diseases. It may be possible that antigen from keratinocytes can produce ETAF, and that IL1 activating T lymphocytes and histiocytes also produce IL1 activating T cells, particularly helper/inducer T cells. Such activities would further promote the increase of B cell function and immunoglobulin synthesis. PMID- 7798428 TI - Probable mechanisms of loss of Merkel cells in completely depigmented skin of stable vitiligo. AB - Vitiligo is frequently associated with segmental involvement. It spares paralyzed limbs in transverse myelitis. There is spontaneous repigmentation of vitiligo lesional skin (VL) in diabetic neuropathy. Increased neuropeptide in VL and adjacent normal skin of vitiligo (ANS) along with thickened nerve fibers showing ultrastructural abnormalities all indicate a neural pathogenesis (1). Loss of Merkel cells has been observed in early vitiligo lesional skin (2). Recently, catecholamines have been found to play a major role in initiating the cascade of events leading to loss of melanocytes (1, 3, 4). To investigate the presence of Merkel cells in the completely depigmented skin of stable vitiligo (SV), a study was undertaken using TROMA 1, a monoclonal antibody specific for adult Merkel cells. No TROMA 1-positive cells were observed in SV, whereas normal numbers of these cells were seen in ANS. This new finding further supports the hypothesis of neural involvement in vitiligo. PMID- 7798429 TI - Nodulocystic acne: oral gugulipid versus tetracycline. AB - Twenty patients with nodulocystic acne were randomly allocated to one of two treatment schedules: 1) Tetracycline 500 mg or 2) Tab. Gugulipid (equivalent to 25 mg guggulsterone). Both were taken twice daily for 3 months, and both produced a progressive reduction in the lesions in the majority of patients. With tetracycline, the percentage reduction in the inflammatory lesions was 65.2% as compared to 68% with gugulipid; on comparison, this difference was statistically insignificant (P > 0.05). Follow-up at 3 months showed a relapse in 4 cases on tetracyline and 2 cases on gugulipid. An interesting observation was that the patients with oily faces responded remarkably better to gugulipid. PMID- 7798430 TI - Pre-existing cutaneous changes in basal cell carcinomas of the lower extremities. AB - Basal cell carcinomas (BCCs) of the lower extremities are not frequently reported. Some pre-existing or predisposing conditions are thought to be implicated in their development. In this study, we investigated the possible relationships between pre-existing cutaneous changes and the development of BCCs of the lower extremities, possible sex and age differences, and the histologic patterns involved. Among 1053 patients with BSSc, BCCs of the lower extremities were observed in 48 (4.5%): 25 men and 23 women. Lesions appeared on the thighs (16 cases), the lower legs (27 cases), or the feet (5 cases). Histologic patterns were nodular and micronodular (18 cases), superficial (27 cases), or infiltrative (3 cases). No differences were observed between sexes. The relative degree of elastosis was higher in the lower limbs of women than of men (2.25 vs 1.53). Pre existing cutaneous changes were observed in 7 cases. The frequency of these BCCs of the lower limbs and the higher degree of elastosis observed in the women seem to be related to sun exposure. The histologic pattern seems not to be affected by environmental factors but rather characteristic of body site. Pre-existent cutaneous changes are not thought to be possible etiologic factors. PMID- 7798431 TI - The rash of measles is caused by a viral infection in the cells of the skin: a case report. AB - Measles skin rash was immunohistochemically examined in an effort to detect virus antigen in skin samples taken from a 15-year-old girl with measles. A sectioned specimen obtained by punch biopsy from a 2nd-day skin lesion showed localized parakeratosis and acanthosis with multinucleated giant cells in the epidermis, thickening and cellular edema of epithelia in the hair follicles, and vascular dilation in the papillary plexus. Measles virus antigen was detected by ABC immunoperoxidase in the epidermis, follicular epithelia, and lympho-histiocytic cell infiltrates in the upper of the dermis. This rash deemed to be caused in part by direct viral infection of the epidermal cells. PMID- 7798432 TI - An aggressive spindle cell squamous carcinoma arising in a patient with long standing erythroderma. AB - Spindle cell squamous carcinoma (SCSC) of the left hand arising in a patient with long-standing erythroderma is reported. Histopathologically, spindle shaped atypical cells were observed neighboring the cells of well differentiated squamous cell carcinoma. These two types of tumor cells, spindle cells and well differentiated cells, were present side by side and merged into each other. The erythroderma had been present for over 20 years, and both clinical and histopathological findings suggested cutaneous T cell lymphoma, but were not diagnostic for mycosis fungoides, Sezary syndrome, or adult T cell lymphoma. Flow cytometry of peripheral blood cells showed a low CD4/CD8 ratio which suggested impaired T cell function. Multiple metastases of SCSC occurred in a short period and the patient died ten months after his first visit to us. The aggressive course of this case was unusual, and may be due to immunological abnormalities associated with the long standing erythroderma with impaired T cell function. PMID- 7798433 TI - Nodular scleroderma in a worker using a silica-containing abrasive. AB - A patient with progressive systemic sclerosis and high levels of serum IgE developed multiple papules at/on an area of non-sclerotic skin. Histologic examination of the papule revealed the typical features of scleroderma. For several years, the patient had been working on polishing watches with an abrasive agent composed mainly of aluminum, chromium dioxide, and silica. An association of the abrasive agent, especially of the silica component, with the scleroderma was circumstantially suspected. To the best of our knowledge, this is the first report of nodular scleroderma which occurred in the course of PSS being associated with chemical agents. PMID- 7798434 TI - Neural blockade, urokinase and prostaglandin E1 combination therapy for acute digital ischemia of progressive systemic sclerosis. AB - To treat severe painful digital ulcers on progressive systemic sclerosis (PSS) patients, we developed a new combination therapy which included neural blockade, intravenous urokinase, and prostaglandin E1 infusion. All of these are already recognized treatments for circulatory disturbances in PSS. Although each of them alone has a limited effect on the painful ischemic attack in PSS; in stepwise combination, neural blockade for release of vascular spasm and pain, prostaglandin E1 for further vasodilatation, and urokinase for thrombolysis were effective in the treatment of digital ischemia in two PSS patients. This therapy reduced the necrotic areas predicted before therapy and saved fingers from amputation. It also relieved the intolerable digital pain and effected the recovery of digital function. PMID- 7798435 TI - Mid dermal elastolysis: case report and review of the literature. AB - A new case of typical mid dermal elastolysis was studied with electron microscopy. Elastic fibers were irregularly branched or lumpy, but subcomponents of these fibers were often normal. In some fibers, loose assembly of skeleton fibrils and aggregation of dense substances were observed. Phagocytosis of normal and abnormal elastic fibers by dermal macrophages was observed. PMID- 7798436 TI - Interferon-alpha (INF-alpha) and etretinate in the treatment of mycosis fungoides. AB - A combination therapy of mycosis fungoides (MF) with interferon-alpha (INF-alpha) and etretinate was reported. A 53-year-old patient suffering from MF was treated with intramuscular administration of INF-alpha at a dosage of 9 x 10(6) IU daily; skin lesions poorly responded to the treatment. After oral etretinate with a dosage of 50 mg daily was combined with INF-alpha, marked clinical improvement was seen in skin lesions with minor side effects. INF-alpha in combination with etretinate can have beneficial effects in the treatment of MF. PMID- 7798437 TI - Three cases of organoid nevus on the trunk and extremity. AB - Organoid nevi are most commonly observed on the scalp. Although they are rarely found on the trunk and extremities, we were able to study 3 cases of organoid nevi involving distributions of this sort. These included a 39-year-old male with a 2 x 6 cm brown area on the left flank (case 1), an 8-year-old female with a 5 x 6 cm hypopigmented macule on the lower left leg (case 2), and a 45-year-old male with a 1.5 x 3 cm brown spot on the back (case 3). All these were histopathologically confirmed to be organoid nevi. The lesion in case 1 revealed basal cell epithelioma, that in case 2 exhibited hypohidrosis caused by poorly developed sweat glands, and the lesion in case 3 was typical, as was an additional one on the same patient's scalp. PMID- 7798438 TI - A case of giant cell tumor of the tendon sheath developing on the palm. AB - A 22-year-old Japanese woman with a giant cell tumor of the tendon sheath on the palm is described. The location of the tumor is rare. Light microscopically, the tumor consisted of round or polygonal cells, giant cells, and foam cells. Electron microscopically, histiocyte-like cells and fibroblast-like cells were mainly observed, suggesting that the tumor may have originated from the synovial membrane. PMID- 7798439 TI - Two cases of eosinophilic pustular folliculitis treated by acemetacin. AB - The report deals with two cases of eosinophilic pustular folliculitis in a 45 year-old man and a 25-year-old woman. After their conditions failed to respond to oral and topical corticosteroids, minocycline, anti-allergic drugs, aspirin and several types of nonsteroidal anti-inflammatory drugs, good results were obtained with acemetacin. PMID- 7798440 TI - Hepatitis C virus infection and oral erosive lichen planus. PMID- 7798441 TI - Airway resistance--an old friend re-visited. PMID- 7798442 TI - Splanchnic perfusion in shock. PMID- 7798443 TI - Predicting bacteremia in critically ill patients: a clinically relevant effort? PMID- 7798444 TI - Tracheal gas insufflation reduces the tidal volume while PaCO2 is maintained constant. AB - OBJECTIVE: The aims of the present study were two-fold: first, to confirm the effect of tracheal gas insufflation (TGI) throughout the respiratory cycle on alveolar ventilation at various catheter flows and constant total inspired VT as an adjunct to conventional volume cycled mechanical ventilation in patients with acute lung injury; second, to test the efficacy of TGI in the reduction of toal VT, peak and mean airway pressure while maintaining PaCO2 in its baseline value. The hemodynamic effect and the consequences on oxygenation as result of the reduction of VT, were also estimated. DESIGN: Prospective study of patients with acute lung injury requiring mechanical ventilation. SETTING: 12 bedded, adult polyvalent intensive care unit in a teaching hospital. PATIENTS: 7 paralyzed and sedated patients with acute respiratory failure were studied. All patients were clinically and hemodynamically stable without fluctuation of the body temperature. All patients were orally intubated with cuffed endotracheal tubes, and mechanically ventilated with a standard circuit of known compliance. INTERVENTIONS: Continuous flows (4 and 6 l/min) were delivered through a catheter positioned 1 cm above carina while tidal volume or PaCO2 were maintained constant at their baseline value. RESULTS: In this study a modest level of TGI significantly enhanced CO2 elimination in patients with acute respiratory failure. Improved ventilatory efficiency resulted from the functional reduction of dead space during TGI allowing the same PaCO2 to be maintained at the same frequency with lower tidal volume and lower airway pressure requirement. Tidal volume, peak and mean airway pressure decreased linearly with catheter flow, without significant changes in oxygenation, while PaCO2 remained stable. CONCLUSION: The results of this study suggest that TGI may be an useful adjunct mode of mechanical ventilation that limits alveolar pressure and minute ventilation requirements. PMID- 7798445 TI - Heterogeneous regional vascular responses to simulated transient hypovolemia in man. AB - OBJECTIVE: To describe the evolution of systemic and regional blood flows during and after hypovolemia in humans. DESIGN: Simulation of hypovolemia by a prolonged application of lower body negative pressure (LBNP). SETTING: Laboratory of Clinical Research, Surgical Intensive Care Unit of an University Hospital. PARTICIPANTS: 8 healthy male volunteers. INTERVENTIONS: 3 successive and increasing 15 min-levels of LBNP were followed by a progressive return (10 min) to atmospheric pressure, then a 60 min-recovery period. MEASUREMENTS AND MAIN RESULTS: Simulated hypovolemia induced a parallel one-third decrease in cardiac output (bioimpedance), musculocutaneous (venous plethysmography) and splanchnic (ICG clearance) blood flows. Adrenergic-mediated peripheral vasoconstriction prevented any change in mean arterial pressure. The decrease in renal blood flow (PAH clearance) was limited, glomerular filtration rate (inulin clearance) unchanged and thus filtration fraction increased. All the cardiovascular and biological variables returned to pre-LBNP values during the recovery period except for splanchnic blood flow which remained below control values 60 min after the return to atmospheric pressure. CONCLUSIONS: Since a sustained splanchnic vasoconstriction follows a transient normotensive hypovolemia in healthy men despite adequate treatment considering arterial pressure and cardiac output, the therapeutic goals of fluid resuscitation after hypovolemic shock might be revisited and a supranormal value of cardiac output proposed. PMID- 7798446 TI - Evaluation of respiratory system resistance in mechanically ventilated patients: the role of the endotracheal tube. AB - OBJECTIVE: To investigate the role played by the endotracheal tube (ETT) in the correct evaluation of respiratory system mechanics with the end inflation occlusion method during constant flow controlled mechanical ventilation. SETTING: General ICU, university of Rome "La Sapienza". PATIENTS: 12 consecutive patients undergoing controlled mechanical ventilation. METHODS: We compared the values of minimal resistance of the respiratory system (i.e. airway resistance) (RRS min) obtained: i) subtracting the theoretical value of ETT resistance from the difference between P max and P1, measured on airway pressure tracings obtained from the distal end of the ETT; ii) directly measuring airway pressure 2 cm below the ETT, thus automatically excluding ETT resistance from the data. RESULTS. The values of RRS min obtained by measuring airway pressure below the ETT were significantly lower than those obtained by measuring airway pressure at the distal end of the ETT and subtracting the theoretical ETT resistance (4.5 +/- 2.8 versus 2.5 +/- 1.6 cm H2O/l/s, p < 0.01). CONCLUSION: When precise measurements of ohmic resistances are required in mechanically ventilated patients, the measurements must be obtained from airways pressure data obtained at tracheal level. The "in vivo" positioning of ETT significantly increases the airflow resistance of the ETT. PMID- 7798447 TI - Can bacteremia be predicted in surgical intensive care unit patients? AB - OBJECTIVES: To determine which clinical features are associated with bacteremia in a SICU. To determine if infections are identified prior to bacteremia via culturing of other body fluids. To determine if antibiotic regimens are changed after the results of the blood culture were obtained. DESIGN: A retrospective, unit-based, case control study. SETTING: A 10 bed SICU in a 552-bed, tertiary care and Level I Trauma center. PATIENTS: All SICU patients with one or more positive blood cultures over a 2 year period (n = 24) were matched by diagnosis, procedure, and age to SICU patients with negative blood cultures (n = 48). MEASUREMENTS AND RESULTS: Bacteremic and control patients had similar APACHE II scores though death was more likely in bacteremic patients (p < 0.05) and they had higher hospital charges (p < 0.02). There was no difference in any of the clinical variables studied (minimum and maximum temperature, maximum white blood cell count, minimum mean arterial blood pressure) between the bacteremic and control groups on the days leading up to and the day of the positive blood culture. Coincident infections of lung, bladder, wound, and central venous catheters were identified in 42% of bacteremic patients. The identification of organisms found in the blood had a direct impact on the antibiotic regimen of 54% of the bacteremic patients. CONCLUSIONS: A better screen for obtaining blood cultures in this SICU was not identified. If antibiotics are begun empirically before the results of blood cultures are known, the results of other body fluid cultures can be used to guide therapy initially. However, the data obtained from positive blood cultures was often helpful in changing empirical therapy. Therefore, blood cultures remain important diagnostic tools. PMID- 7798448 TI - Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients. AB - OBJECTIVE: To investigate the influence of continuous haemofiltration (CHF) on haemodynamics, gas exchange and core temperature in critically ill septic patients with acute renal failure. PATIENTS AND METHODS: In 20 patients (17 male, 3 female) ultrafiltration rate, core temperature, gas exchange and haemodynamic variables were measured at regular intervals during the first 48 h of haemofiltration. Baseline data were compared to those obtained 30 min after initiating CHF and also to those during hypothermia (if observed). MAIN RESULTS: Haemodynamic variables remained remarkably constant throughout the study period. In patients with a relatively low ultrafiltration rate (855 +/- 278 ml/h) temperature did not change, while in patients with a high ultrafiltration rate (1468 +/- 293 ml/h) core temperature significantly decreased from 37.6 +/- 0.9 degrees C to 34.8 +/- 0.8 degrees C (p < 0.001). There was a statistically significant correlation between temperature decrease and ultrafiltration rate (r = -0.68, Y = 1.8-0.003 X, p < 0.01). Hypothermic patients also showed a mean decrease in VO2 from 141 +/- 22 ml/min/m2 to 112 +/- 22 ml/min/m2 (p < 0.01) with a concomitant increase in PaO2 from 103 +/- 37 mmHg to 140 +/- 42 mmHg (p < 0.001) and in PvO2 from 35 +/- 4 mmHg to 41 +/- 5 mmHg (p < 0.001). CONCLUSIONS: 1) Continuous haemofiltration does not cause significant alternations in haemodynamic variables. 2) Hypothermia frequently occurs in patients undergoing continuous haemofiltration with high ultrafiltration rates. These hypothermic patients show a reduction in VO2 leading to an increase in PvO2 and PaO2. This mild hypothermia in these circumstances has no evident deleterious effects. PMID- 7798450 TI - Non-operative management of gastric perforation secondary to cardiopulmonary resuscitation. AB - We report the case of a 72-year-old male who suffered a cardiac arrest during an early positive treadmill stress test. After successful resuscitation the patient had evidence of a gastric perforation. Because of his hemodynamic stability, lack of peritoneal signs, and prohibitively high surgical risk, a non-operative management approach was successfully administered. Although not the standard approach to traumatic gastric perforation, this case is not unlike the management of peptic ulcer perforations. A non-operative approach should be considered as an option in selected patients. PMID- 7798449 TI - Severe malaria in African adults living in a seasonal endemic area. AB - OBJECTIVE: This study investigates severe malaria in African adults living in a seasonal endemic area. DESIGN: A prospective study of all adults admitted with severe malaria over 2 consecutive seasons: October 1990 till January 1991 and October 1991 till January 1992. SETTING: ICU (15 beds) of Hopital Principal, Dakar, Senegal. PATIENTS: 23 patients: 14 men and 9 women with a mean age of 30 +/- 3 years were included in the study; all fulfilled the 1990 WHO criteria for severe malaria. RESULTS: At admission, 12 patients were comatose (Glasgow Coma Scale < 10), 7 had generalized convulsions. Parasitaemia was 135 +/- 52 x 10(9)/l. Biological indications of severity were as follows: hypophosphataemia < 0.8 mmol/l in 14 cases, serum creatine phosphokinase > 500 IU/l in 15 cases; and PaO2 < 70 mmHg in 5 cases. Serum TNF alpha levels, measured in 16 cases, were increased at 298.4 +/- 63.5 pg/ml, serum levels of IL-6 and IL-2SR were also elevated: 609.5 +/- 304.2 pg/ml and 297.6 +/- 35.6 pg/ml respectively. Circulating IgM and IgG antibodies were found in 14 out of 16 patients. Serum levels of TNF alpha, IL-6 and IL-2SR correlated positively with each other. TNF alpha and IL-2SR were also positively correlated to parasitaemia. Intravenous therapy with quinine at loading dose was favorable in 19 patients. Four patients died during the study, 3 from multiple organ failure. CONCLUSIONS: This work demonstrated that severe malaria in a seasonal endemic area displays original clinical features with a high rate of either cerebral malaria or multiple organ failure. PMID- 7798452 TI - The use of the laryngeal mask airway to facilitate the insertion of a percutaneous tracheostomy. AB - We report the use of the laryngeal mask airway to facilitate the insertion of a percutaneous tracheostomy (Ciaglia kit) in two patients. This method has not been reported previously. We believe that in selected patients the technique described increases the ease of placement of a percutaneous tracheostomy. PMID- 7798451 TI - Effects of norepinephrine on right ventricular function in septic shock patients. AB - OBJECTIVE: To study the effects of norepinephrine on right ventricular function in patients with hyperdynamic septic shock. DESIGN: Prospective, open study. SETTING: A 15 bed ICU in a university hospital. PATIENTS: 9 patients with hyperdynamic septic shock (SBP < 90 mmHg, Cl > or = 4 l.min-1.m-2, SVRI < or = 850 dynes.s.cm-5m-2 and oliguria). INTERVENTIONS: Plasma volume expansion was used to correct a suspected volume deficit and then, norepinephrine infusion was started and titrated to restore systemic blood pressure to the normal range (mean infusion rate: 1.1 +/- 0.2 mcg.kg-1.min-1). Norepinephrine was the only vasoactive agent used in these patients. MEASUREMENTS AND RESULTS: A modified Swan-Ganz catheter mounted with a fast response thermistor was inserted in each patient, allowing repeated measurements of RVEDVI and RVEF. At time of inclusion to the study, all but one patient had elevated MPAP (23 +/- 4 mmHg) and RVEF < or = 50%, and all patients had RVEDVI > or = 90 ml.m-2. During norepinephrine infusion, MAP increased from 51 +/- 9 to 89 +/- 10 mmHg (p < 0.0001), PVRI increased from 204 +/- 35 to 286 +/- 63 dynes.s.cm-5.m-2 (p < 0.05), and despite this increase in right ventricular afterload, no detrimental effect in RVEF (36 +/- 11 to 36 +/- 10%) or in RVEDVI (116 +/- 30 to 127 +/- 40 ml.m-2) was observed. A Frank-Starling relationship for the right ventricle was constructed by plotting an index of ventricular performance (RVSWI) against an index of ventricular preload (RVEDVI). A significant upward shift to the right of the relationship was observed during norepinephrine infusion. CONCLUSION: It was concluded that norepinephrine exerted a favourable effect on right ventricular function. PMID- 7798453 TI - Usefulness of central venous oxygen saturation monitoring during cardiopulmonary resuscitation. A comparative case study with end-tidal carbon dioxide monitoring. AB - The usefulness of continuous monitoring of central venous oxygen saturation (ScvO2) in comparison with the capnogram during cardiopulmonary resuscitation (CPR) was demonstrated in a cardiac arrest patient. ScvO2 and end-tidal carbon dioxide (ETCO2) decreased following cessation of chest compression or increased during recovery of systemic circulation. During the complete stasis of systemic circulation, when defibrillation was done, ScvO2 did not change, while ETCO2 gradually decreased. However the larger decrease in ScvO2 temporally occurred when chest compression was resumed. And also the ScvO2 monitoring had great advantage to detecting peripheral tissue oxygenation. ScvO2 seems to be no less accurate and reliable monitoring than the capnogram during CPR procedures. Since the capnogram is non-invasively and easily used in cardiac arrest patients, ScvO2 monitoring combined with the capnogram is a more preferable method for assessing the efficacy of ongoing CPR. PMID- 7798454 TI - Tonometry to assess the adequacy of splanchnic oxygenation in the critically ill patient. AB - Tonometry, a relatively non-invasive technique for indirectly measuring the intramucosal pH (pHi) of the gastrointestinal tract, has recently been developed for use in critically ill patients. Reports in the literature suggest that the technique is of greatest benefit to patients at risk of developing reductions in splanchnic oxygenation (decreased O2 delivery) in whom early detection of the ischemic episode could possibly guide treatment. Tonometry, although still at a relatively early stage in its clinical development, could be of value for selected patient groups although further evaluation of the technique is necessary. PMID- 7798455 TI - Continuous veno-venous hemofiltration and mortality after cardiac surgery. PMID- 7798456 TI - Reversed Fick principle versus indirect calorimetry: do systematic differences between methods represent intrapulmonary oxygen consumption? PMID- 7798457 TI - Impact of SDD on ICU ecology. PMID- 7798458 TI - Isoflurane sedation and atmospheric pollution. PMID- 7798459 TI - The reliability of endotoxin and cytokine measurements in polytrauma patient and their relationship to the development of sepsis. PMID- 7798460 TI - Prolonged paralysis after long-term infusion of neuromuscular blocking agents. PMID- 7798461 TI - The role of psychosocial and biological variables in separating chronic and non chronic major depression and early-late-onset dysthymia. AB - Psychosocial (sociodemographic characteristics, loss and separation and family atmosphere in childhood, recent life events) and biological (family history, DST, TRH-test) variables were investigated in 180 patients with Major Depression (MD) and Dysthymic Disorder (DD). The aim of the study was to reveal certain differences between the chronic and non-chronic course of MD and the early- and late-onset subtypes of dysthymia. When comparing the two course patterns of MD, a higher rate of malignant tumours among first-degree relatives, a greater number of long-lasting stress situations before the index depressive episode, longer duration of the previous episodes, less frequent DST nonsuppression, and a blunted TSH response to TRH were found in patients with a chronic course of MD. Several factors seem to influence the course pattern of MD, or else the chronic form represents a subgroup within MD. The late-onset dysthymics were mainly women with a low level of education, a lower suicidal tendency, normal suppression in DST, and a lack of blunted TSH responses to TRH administration during the period of double depression. The early-onset dysthymics showed a higher number of persons who had never married, who presented a more traumatic and frustrating childhood background, and who had a higher rate of DST non-suppressors and blunted TSH responses after TRH administration during the period of their double depression. Our data suggest that late-onset dysthymia might be a biologically distinct subgroup of chronic depression. PMID- 7798462 TI - Decreased hedonic responsiveness during a brief depressive mood swing. AB - Female volunteers completed the Fawcett-Clark Pleasure Capacity Scale (FCPCS) and rated the pleasantness and desirability of a taste stimulus (cheese), before and during a depressive mood swing. Mood change was induced by reading negative self referent statements, with additional 'booster' periods of mood induction to prolong the duration of the mood swing. The mood induction procedure (MIP) caused a decrease in contentment and alertness, as derived from a set of visual analogue mood scales, and also decreased hedonic capacity, as measured by responses to the taste stimulus and by the FCPCS. No changes on any measure were shown by a control group who read an equivalent set of positive self-referent statements. Prior to the MIP, there were no significant correlations between mood measures and hedonic measures, or between taste responses and the FCPCS. However, there were significant correlations between the size of the changes in these various measures following the depressive MIP. The results suggest that hedonic capacity is responsive to acute depressive mood swings. PMID- 7798463 TI - Effects of exclusion criteria in depression treatment studies. AB - We investigated the effects of exclusion criteria in depression treatment studies by applying simulated exclusion criteria to a relatively unselected sample. The criteria were borderline personality disorder, drug/alcohol dependence, and exclusion criteria from the Treatment of Depression Collaborative Research Program and the Maintenance Therapies for Recurrent Depression Protocol. Each set of criteria substantially distorted demographic characteristics and Axis I and II comorbidity but did not yield higher rates of study completion or, in general, response to tricyclics. Excessive exclusion criteria in depression treatment studies have many adverse effects and should be applied only when overwhelmingly compelling reasons exist. PMID- 7798464 TI - Binding of [3H]paroxetine to platelets of depressed patients: seasonal differences and effects of diagnostic classification. AB - [3H]Paroxetine is a more reliable ligand for studying the serotonin (5-HT) transporter complex than [3H]imipramine. The present study investigates [3H]paroxetine binding to platelets in 54 depressed in-patients (18 minor, 16 simple major and 20 melancholic depressed patients) and 16 healthy controls. There were no significant differences in maximal number of binding sites between depressed subjects and normal controls. There was no correlation between [3H]paroxetine binding to platelet membranes and severity of depression. [3H]Paroxetine binding to platelets was significantly higher in spring than in summer, fall and winter. PMID- 7798465 TI - Acute tryptophan depletion aggravates premenstrual syndrome. AB - The dietary technique of acute tryptophan depletion was used to suppress brain serotonin synthesis in 16 women with documented premenstrual syndrome. Each subject was tested at distinct phases of each of two menstrual cycles. Baseline amino acid levels did not vary across the menstrual cycle, except for tyrosine which showed a significant premenstrual decrement. Compared to a sham procedure, actual tryptophan depletion caused a significant aggravation of premenstrual symptoms, particularly irritability. Symptom magnitude was correlated with diminution of tryptophan relative to other amino acids. This result supports other evidence implicating serotonin in premenstrual syndrome. PMID- 7798466 TI - Do depressed patients with higher pretreatment stress levels respond better to cognitive therapy than imipramine? AB - Forty-eight unipolar depressed patients were randomly assigned to 12 weeks of treatment with either imipramine (IMI) (n = 32) or cognitive therapy (CT) (n = 16). Prior to treatment assignment, all patients were rated for severity of a variety of psychosocial stressors. The interaction effect between pretreatment stress and type of treatment, CT or IMI, on symptom improvement was evaluated. We hypothesized that patients with greater pretreatment stress would respond better to cognitive therapy. Patients treated with either CT or IMI showed equivalent reductions of depressive symptoms. There was no interaction effect between pretreatment stress and type of treatment on improvement of depressive symptoms. Based on this preliminary study it does not appear that depressed patients with higher pretreatment levels of stress respond better to cognitive therapy than they do to imipramine. PMID- 7798467 TI - Panic attacks and panic disorder in Japanese non-patient population: epidemiology and psychosocial correlates. AB - To investigate the prevalence rates of panic disorder and panic attacks in the general population of Japan, a set of questionnaires were administered to 207 people aged 18 or over, who were then interviewed. Seven (3.4%) had experienced one or more unexpected panic attacks in their lifetime. Two subjects (1.0%) had had panic disorder (DSM-III-R), and five (2.4%) had had panic attacks not meeting the criteria for panic disorder. Seventy percent of the persons with panic disorder or panic attacks had sought medical care. There was comorbidity with agoraphobia in two cases, and with major depression in five. Harsh discipline, frequent quarrel, between parents, and serious illness before the age of 16 were more frequent in individuals suffering from panic attacks, compared to those without. PMID- 7798468 TI - The relationship of premorbid personality to subtypes of an affective illness. A replication study by means of an operationalized procedure for the diagnosis of personality structures. AB - The hypothesis of a relationship between types of premorbid personality and subtypes of an affective illness was tested on the basis of a diagnostically 'blind' assignment of biographical case history data on patients' premorbid development to patterns of personality traits. Data sets of 261 cases with various psychiatric disorders were examined. The rater (R.T.) had to score each item in a list of traits relevant for the diagnosis of the types that had been conceived by D.v.Z. and J.P. The assignment of the ratings to the type concepts was then performed by means of a computer programme. The results regarding the distribution of types over the clinical diagnoses yielded a statistically significant association of the 'affective types' of premorbid personality ('melancholic type' and 'manic type') with affective disorders and the 'neurotoid types' ('anxious insecure type' and 'nervous tense type') with non-affective disorders. Previous findings on the basis of a global rating of types in a smaller sample (n = 42) regarding personality types and subtypes of an affective illness could be replicated by means of the new, operationalized procedure in an enlarged sample (n = 80): On the one hand, a marked preponderance of the 'manic type' of personality was found in bipolar I patients, particularly pronounced in those with a predominantly manic course of the disorder; on the other hand, the 'melancholic type' of personality prevailed in bipolar II and unipolar depressive patients. PMID- 7798469 TI - A world without water fluoridation. PMID- 7798470 TI - Surgical, nonsurgical therapies. PMID- 7798471 TI - Economic compression. PMID- 7798472 TI - Specialty and general practice communication. PMID- 7798473 TI - Local anesthetics: dentistry's most important drugs. AB - One hundred and fifty years ago, Horace Wells opened the door to local anesthetics. Since then, many advances have been made in pain control. The development of dentistry's most important drugs is highlighted here. PMID- 7798474 TI - Dentistry's answer to 'the humiliating spectacle'. Dr. Wells and his discovery. PMID- 7798476 TI - What others said about Wells. Memorials, tributes, affirmations. PMID- 7798475 TI - Remembering Dr. Menczer. Champion of Horace Wells. PMID- 7798477 TI - Dr. Wells' impact on dentistry and medicine. PMID- 7798478 TI - Spotlight on today's major issues. Five share their views. PMID- 7798479 TI - Panoramic radiography: an aid in detecting patients at risk of cerebrovascular accident. AB - Some individuals at risk for a cerebrovascular accident can be identified in the dental office by appropriate review of their panoramic radiographs. Radiographs were evaluated for 304 outpatients, 55 years or older, to check the presence of calcifications associated with artery disease. Three percent of the sample had such opacities. PMID- 7798480 TI - Epidemiology of chronic facial pain: diagnostic usefulness in patient care. AB - Three chronic facial pain conditions--temporomandibular pain and dysfunction syndrome, phantom tooth pain and burning mouth syndrome--can puzzle dentists trying to provide diagnoses and treatment plans. Epidemiologic data and their usefulness in providing diagnostic criteria for these conditions are explored. PMID- 7798481 TI - Treating severe partial anodontia: a 10-year history of patient treatment. AB - Severe partial anodontia is relatively rare. This case report describes the 10 year treatment history of a patient with partial anodontia, beginning with removable partial overlay dentures and culminating with fixed implant prostheses. PMID- 7798482 TI - Treating growth and TMJ abnormalities in juvenile rheumatoid arthritis. AB - Two case reports illustrate the orofacial aspects of juvenile rheumatoid arthritis. The disease can affect facial growth and cause TMJ abnormalities. Children may vary in the degree to which they are affected by JRA, and dentists should investigate JRA as a cause of these abnormalities or deformities. PMID- 7798483 TI - Staying excited about dentistry. PMID- 7798484 TI - 26th Bethesda Conference: recommendations for determining eligibility for competition in athletes with cardiovascular abnormalities. January 6-7, 1994. PMID- 7798485 TI - COCATS Guidelines. Guidelines for Training in Adult Cardiovascular Medicine, Core Cardiology Training Symposium. June 27-28, 1994. American College of Cardiology. PMID- 7798486 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 2: training in electrocardiography, ambulatory electrocardiography and exercise testing. PMID- 7798487 TI - Left ventricular function in chronic mitral regurgitation: preoperative and postoperative comparison. AB - OBJECTIVES: The present study was designed to evaluate the effects of surgical procedure on left ventricular systolic and diastolic function in patients with mitral regurgitation. BACKGROUND: Left ventricular systolic function has been shown to decline after operation in patients with chronic mitral regurgitation. METHODS: Using simultaneous cineangiography and left ventricular micromanometry, we evaluated left ventricular systolic and diastolic function in 14 patients with chronic mitral regurgitation both preoperatively and at an average of 22 months after operation. Eight patients underwent mitral valve reconstruction, and six had a valve replacement with interruption of the chordae tendineae. We compared these patients with 10 control subjects. RESULTS: Preoperatively, patients with mitral regurgitation demonstrated normal global and regional left ventricular systolic function. Peak rate of diastolic filling was increased (p < 0.01), and passive chamber stiffness was decreased, compared with that in control subjects (p < 0.01), and there was normal myocardial stiffness. Postoperatively, systolic and diastolic function returned to normal in patients undergoing mitral valve reconstruction. In contrast, global systolic function was depressed in patients after valve replacement (p < 0.05), with regional dysfunction in the area of papillary muscle attachment (p < 0.01). Diastolic function was depressed in this group, with a prolonged time constant of pressure decay (p < 0.01) and a depressed rate of early diastolic filling and strain rate (p < 0.05). Passive elastic stiffness was within the normal range in all postoperative patients. CONCLUSIONS: The type of operation performed to correct chronic mitral regurgitation has an important effect on postoperative left ventricular function. Systolic and diastolic function are preserved after mitral valve reconstruction. Mitral valve replacement with chordal interruption is associated with global and regional systolic dysfunction and early diastolic filling and relaxation abnormalities. PMID- 7798488 TI - Effect of dobutamine stress echocardiography on mitral regurgitation. AB - OBJECTIVES: This study was performed to examine the effect of dobutamine stress echocardiography on mitral regurgitation and to test the hypothesis that mitral regurgitation will increase in patients with an ischemic response. BACKGROUND: New or worsening mitral regurgitation during stress testing has been proposed as a marker of ischemia. However, it is unclear whether ischemia induced by dobutamine is associated with mitral regurgitation because the hemodynamic effects of dobutamine may vary with regard to mitral regurgitation, depending on left ventricular function and maximal dose attained. METHODS: Dobutamine stress echocardiography was performed in 102 consecutive patients with suspected or known coronary artery disease. Color flow Doppler was used to determine the presence and change in mitral regurgitation at baseline and peak dobutamine infusion (up to 40 micrograms/kg body weight per min). The mitral regurgitation color flow Doppler area was semiquantitatively graded as mild (< 4 cm2), moderate (4 to 8 cm2) or severe (> 8 cm2). Patients were assigned to ischemic and nonischemic groups according to the dobutamine stress echocardiographic results. RESULTS: The two groups achieved the same maximal dose and demonstrated similar blood pressure and heart rate responses to dobutamine infusion. Only two patients developed new mitral regurgitation during dobutamine infusion, and both had a normal dobutamine echocardiographic result. More patients without ischemia had no mitral regurgitation compared with patients with ischemia. There was an insufficient number of patients with coronary angiographic data to determine the effects of mitral regurgitation on the sensitivity and specificity of dobutamine stress echocardiography. Of 23 patients with a rest ejection fraction < 50%, 61% had an improvement in mitral regurgitation grade compared with 25% of patients with a rest ejection fraction > or = 50% (p < 0.02). CONCLUSIONS: These data indicate that although dobutamine infusion often improves mitral regurgitation in patients with left ventricular dysfunction during stress echocardiography, it does not induce or worsen mitral regurgitation in those who demonstrate an ischemic response. Future studies are necessary, with large numbers of patients, to determine the effects of mitral regurgitation on the sensitivity and specificity of dobutamine stress echocardiography. PMID- 7798489 TI - Observations suggesting a high incidence of exercise-induced severe mitral regurgitation in patients with mild rheumatic mitral valve disease at rest. AB - OBJECTIVES: The aim of this study was to determine the hemodynamic effects of upright bicycle ergometry in symptomatic patients with mild, mixed mitral stenosis and regurgitation. BACKGROUND: Patients with seemingly mild rheumatic mitral valve disease often complain of exertional dyspnea or fatigue. These symptoms are usually ascribed to flow-dependent increases in the gradient across the stenotic mitral valve. Although catheterization studies in these patients may demonstrate an increase in mitral valve gradient proportional to an increase in cardiac output, this approach does not specifically address the underlying mechanism of any observed increases in mitral gradient or left atrial (i.e., pulmonary capillary wedge) pressure. Exercise echocardiography is uniquely suited to the dynamic assessment of exercise-induced hemodynamic changes. METHODS: Fourteen symptomatic patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest performed symptom-limited upright bicycle ergometry with quantitative two-dimensional, Doppler and color Doppler echocardiographic analysis. RESULTS: Average pulmonary artery systolic pressure in the 13 patients with adequate spectral signals of tricuspid regurgitation increased from 36 +/- 5 mm Hg (mean +/- SD) at rest to 63 +/- 14 mm Hg at peak exercise (p < 0.001). The mean transmitral pressure gradient in all patients increased from 4.5 +/- 1.4 mm Hg at rest to 12.7 +/- 2.7 mm Hg at peak exercise (p < 0.001). Five patients developed severe mitral regurgitation during exercise. CONCLUSIONS: Patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest demonstrate a marked increase in pulmonary artery systolic pressure and mean transmitral pressure gradient during dynamic exercise. In a subset of these patients, marked worsening of mitral regurgitation appears to be the underlying mechanism of this hemodynamic deterioration. Because of the small sample size, this novel observation must be considered preliminary with respect to the true prevalence of exercise-related development of severe mitral regurgitation. If additional studies confirm the importance of this phenomenon, it has important implications for the management of patients with rheumatic mitral valve disease. PMID- 7798490 TI - Anterior leaflet procedures during mitral valve repair do not adversely influence long-term outcome. AB - OBJECTIVES: This study was done to assess the impact of anterior mitral leaflet reconstructive procedures on initial and long-term results of mitral valve repair. BACKGROUND: It has been suggested that involvement of the anterior leaflet in mitral valve disease adversely affects the long-term outcome of mitral valve repair. Our policy has been to aggressively repair such anterior leaflets with procedures that include triangular resections in some cases. METHODS: From June 1979 through June 1993, 558 consecutive Carpentier-type mitral valve repairs were performed. The anterior mitral leaflet and chordae tendineae were repaired in 156 patients (mean age 58 years). The procedures included anterior chordal shortening in 78 patients (50%), anterior leaflet resections in 44 (28%), resuspension of the anterior leaflet to secondary chordae in 42 (27%) and anterior chordal transposition in 27 (17%). Concomitant cardiac surgical procedures were performed in 75 patients (48%). RESULTS: The operative mortality rate was 2.5% (2 of 81) for isolated mitral valve anterior leaflet repair and 3.8% (6 of 156) for all mitral valve anterior leaflet repair. Freedom from reoperation at 5 and 10 years was, respectively, 89.7% (n = 160) and 83.4% (n = 24) for the entire series of 558 patients, 91.9% (n = 51) and 81.2% (n = 10) for patients with anterior leaflet procedures, 88.8% (n = 109) and 84.4% (n = 14) for patients without anterior leaflet procedures and 91.7% (n = 118) and 88.9% (n = 18) for patients without rheumatic disease. Logistic regression showed that rheumatic origin of disease (odds ratio 2.99), but not anterior leaflet repair, increased the risk for reoperation. CONCLUSIONS: These results demonstrate that expansion of mitral valve techniques to include anterior leaflet disease yields immediate and long-term results equal to those seen in patients with posterior leaflet disease. PMID- 7798491 TI - Pseudoaneurysms of the mitral-aortic intervalvular fibrosa: dynamic characterization using transesophageal echocardiographic and Doppler techniques. AB - OBJECTIVES: The aim of this study was to provide a detailed description of echocardiographic and Doppler features of pseudoaneurysms involving the mitral aortic intervalvular fibrosa and to compare echocardiographic and aortographic findings. BACKGROUND: Infection of the aortic valve may spread to the aortic annulus, resulting in ring abscesses or pseudoaneurysms, or both, of the intervalvular fibrosa, which can alter patient management and prognosis. METHODS: The echocardiographic and Doppler findings of 20 patients with pseudoaneurysms or ring abscesses, or both, were reviewed and compared with surgical and aortographic results. RESULTS: A total of 23 lesions were identified, of which 16 were intervalvular pseudoaneurysms, and 7 were ring abscesses. Transthoracic echocardiography detected 43% of the lesions, whereas transesophageal echocardiography identified 90% (p < 0.01). The most distinct feature of the pseudoaneurysms was marked pulsatility, with systolic expansion and diastolic collapse (mean systolic area [+/- SD] 4.1 +/- 3.4 cm2 vs. diastolic mean area 1.8 +/- 2.2 cm2, p < 0.05). Using color Doppler, two types were identified: unruptured pseudoaneurysms (n = 9), which communicated only with the left ventricular outflow tract and had a distinct flow pattern, and ruptured pseudoaneurysms (n = 7), which, in addition, communicated with the left atrium or aorta. Compared with pseudoaneurysms, ring abscesses were smaller and nonpulsatile and showed either no flow or continuous systolic and diastolic flow, the site of paravalvular aortic insufficiency. In 10 patients who underwent aortography, three lesions were identified, and findings were concordant with echocardiography. However, in seven patients aortographic findings were normal, whereas echocardiography identified intervalvular pseudoaneurysms, all of which were documented at operation. CONCLUSIONS: Intervalvular pseudoaneurysms are more frequently detected by transesophageal echocardiography than by aortography or transthoracic examination and exhibit distinct dynamic features and Doppler patterns that can further help characterize cavitary lesions in the aortic root and guide appropriate surgical intervention. PMID- 7798492 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 3: training in cardiac catheterization and interventional cardiology. PMID- 7798493 TI - Evidence for reduction of norepinephrine uptake sites in the failing human heart. AB - OBJECTIVES: This study investigated the role of neuronal uptake of norepinephrine (uptake-1) in human heart failure as a local factor for altering concentrations of norepinephrine at the cardiac myocyte membranes. BACKGROUND: Several beta adrenergic neuroeffector defects occur in heart failure. Whether an alteration in norepinephrine uptake-1 occurs is still unresolved. METHODS: The role of norepinephrine uptake-1 was studied in electrically stimulated (1 Hz, 37 degrees C) human ventricular cardiac preparations and isolated myocardial membranes. RESULTS: The effectiveness of norepinephrine in increasing the force of contraction was decreased in relation to the degree of heart failure. In contrast, the potency of norepinephrine was increased in failing hearts (New York Heart Association functional class IV) in relation to the concentrations producing 50% of the maximal effect (EC50). The EC50 values for isoproterenol, which is not a substrate for norepinephrine uptake-1, were reduced in myocardium in functional classes II to III and IV compared with those in nonfailing myocardium. The uptake inhibitors cocaine and desipramine (3 mumol/liter) potentiated the positive inotropic effects of norepinephrine in nonfailing myocardium (p < 0.05) but not in functional class IV myocardium. Radioligand binding experiments using the uptake inhibitor hydrogen-3 mazindol revealed a significant decrease by approximately 30% in norepinephrine uptake-1 carrier density in functional classes II to III and IV myocardium versus nonfailing myocardium (p < 0.05). CONCLUSIONS: In human heart failure, there is a presynaptic defect in the sympathetic nervous system, leading to reduced uptake-1 activity. This defect in the failing heart can be mimicked by the effects of uptake blocking agents, such as cocaine and desipramine, in the nonfailing heart only. Compromised norepinephrine uptake-1 in functional class IV cannot be further increased by cocaine and desipramine. The pathophysiologic consequences could be an increased synaptic concentration of norepinephrine predisposing to adenylyl cyclase desensitization. PMID- 7798494 TI - Predictors of systolic and diastolic improvement in patients with dilated cardiomyopathy treated with metoprolol. AB - OBJECTIVES: The aim of this study was to determine which patients will have systolic and diastolic improvement after beta-blockade with metoprolol. BACKGROUND: Beta-adrenergic blocking agents improve systolic and diastolic function in patients with heart failure. However, it is unclear which patients will respond best to therapy. METHODS: We retrospectively examined baseline characteristics of 24 patients who underwent double-blind then open-label treatment with metoprolol to determine which characteristic predicted improvement in systolic and diastolic function. Degree of improvement in systolic function (22 patients) was defined by the change in left ventricular ejection fraction after 3 months of therapy. Degree of improvement in diastolic function (15 patients) was defined as the change in left ventricular end-diastolic pressure and change in the slope of the isovolumetric relaxation rate-end-systolic pressure relation. RESULTS: Both systolic blood pressure at baseline (r = 0.54, p = 0.009) and the maximal positive value of the first derivative of left ventricular pressure with respect to time (peak +dP/dt) at baseline (r = 0.39, p = 0.07) correlated with improvement in ejection fraction after metoprolol treatment. Stepwise logistic regression demonstrated that only peak systolic pressure was an independent predictor of systolic improvement. Baseline heart rate, ventricular volumes, ejection fraction and adrenergic activation, as reflected by coronary sinus norepinephrine, did not predict response. Patients with the most diastolic impairment at baseline had the most favorable diastolic improvement. Those with the lowest myocardial respiratory quotient (most fatty acid utilization) at baseline also had the most marked reduction in left ventricular end-diastolic pressure. CONCLUSIONS: These data suggest that those patients with the highest peak systolic pressure, highest left ventricular end diastolic pressure and most prolonged isovolumetric relaxation at baseline will respond best to therapy with metoprolol. However, other patients without these characteristics may also benefit. PMID- 7798495 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 4: training in echocardiography. PMID- 7798496 TI - Improvement in exercise capacity of candidates awaiting heart transplantation. AB - OBJECTIVES: This study determined the frequency of improvement in peak oxygen uptake and its role in reevaluation of candidates awaiting heart transplantation. BACKGROUND: Ambulatory candidates for transplantation usually wait > 6 months to undergo the procedure, and during this period symptoms may lessen, and peak oxygen uptake may improve. Whereas initial transplant candidacy is based increasingly on objective criteria, there are no established guidelines for reevaluation to determine who can leave the active waiting list. METHODS: All ambulatory transplant candidates with initial peak oxygen uptake < 14 ml/kg per min were identified. Of 107 such patients listed, 68 survived without early deterioration or transplantation to undergo repeat exercise. A strategy of reevaluation using specific clinical criteria and exercise performance was tested to determine whether patients with improved oxygen uptake could safely be followed without transplantation. RESULTS: In 38 of the 68 patients, peak oxygen uptake increased by > or = 2 ml/kg per min to a level > or = 12 ml/kg per min after 6 +/- 5 months, together with an increase in anaerobic threshold, peak oxygen pulse and exercise heart rate reserve and a decrease in heart rate at rest. Increased peak oxygen uptake was accompanied by stable clinical status without congestion in 31 of 38 patients, and these 31 were taken off the active waiting list. At 2 years, their actuarial survival rate was 100%, and the survival rate without relisting for transplantation was 85%. CONCLUSION: Reevaluation of exercise capacity and clinical status allowed removal of 31 (29%) of 107 ambulatory transplant candidates from the waiting list with excellent early survival despite low peak oxygen uptake on initial testing. The ability to increase peak oxygen uptake, particularly with increased peak oxygen pulse, may indicate improved prognosis as well as functional capacity and, in combination with stable clinical status, may be an indication to defer transplantation in favor of more compromised candidates. PMID- 7798497 TI - Incidence and severity of transplant coronary artery disease early and up to 15 years after transplantation as detected by intravascular ultrasound. AB - OBJECTIVES: The purpose of this study was to quantify the severity of transplant coronary artery disease and to assess lesion characteristics early and up to 15 years after heart transplantation by using intracoronary ultrasound. BACKGROUND: Intravascular ultrasound has the ability to measure the components of the arterial wall and has been shown to be a sensitive method for detection of transplant coronary artery disease. METHODS: A total of 304 intracoronary ultrasound studies were performed in 174 heart transplant recipients at baseline and up to 15 (mean 3.3 +/- 0.2) years after transplantation. Mean intimal thickness and an intimal index were calculated, and lesion characteristics (eccentricity, calcification) were assessed for all coronary sites imaged (mean 3.0 +/- 0.1 sites/study). The Stanford classification was used to grade lesion severity. RESULTS: Compared with findings in patients studied at baseline (< 2 months after transplantation, n = 50), mean intimal thickness (0.09 +/- 0.02 vs. 0.16 +/- 0.02 mm, p < 0.01), intimal index (0.07 +/- 0.01 vs. 0.14 +/- 0.02, p < 0.01) and mean severity class (1.5 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly higher at year 1 (n = 52) after transplantation. Thereafter, all three variables further increased over time and reached highest values between years 5 and 15. Calcification of lesions was detected in 2% to 12% of studies up to 5 years after transplantation, with a significant increase to 24% at years 6 to 10 (p < 0.05). CONCLUSIONS: Severity of transplant coronary artery disease appeared to progress with time after transplantation in this cross-sectional study. This characteristic was most prominent during the 1st 2 years after transplantation, whereas calcification of plaques occurred to a significant extent only later in the process. These data may serve as a reference for comparison of intravascular ultrasound findings in other studies of patients with transplant coronary artery disease. PMID- 7798498 TI - Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements. AB - OBJECTIVES: The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND: The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS: Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS: In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS: These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty. PMID- 7798499 TI - Internal thoracic artery grafts: 20-year clinical follow-up. AB - OBJECTIVES: This study compared the long-term clinical results of coronary artery bypass surgery in patients with internal thoracic artery grafts with those in patients with vein grafts only. BACKGROUND: Aortocoronary artery bypass surgery has been performed for > 25 years, primarily utilizing the saphenous vein and internal thoracic artery as conduits. Although the internal thoracic artery has been shown to confer a clinical advantage, it is not known for how many years this benefit will continue. METHODS: All consecutive patients undergoing initial coronary artery bypass surgery between 1970 and 1973 were followed for up to 20 years. Clinical evaluation included survival, late myocardial infarction, need for reoperation and recurrence of angina. Patients were analyzed in three groups: vein grafts only (214 patients); a single internal thoracic artery graft with or without associated vein grafts (490 patients); and bilateral internal thoracic artery grafts (39 patients). Use of the operating microscope was also analyzed with regard to effect on survival. RESULTS: The internal thoracic artery graft and use of the operating microscope were independent predictors of mortality and reduced the risk of dying by a factor of 0.68 and 0.76, respectively. An internal thoracic artery graft resulted in a mean survival of 4.4 years longer than that with vein grafts alone. The internal thoracic artery graft compared with vein grafts was associated with fewer reoperations (p < 0.001), fewer late myocardial infarctions, lower associated mortality rates (p < 0.04) and less early recurrence of angina (p = 0.03). CONCLUSIONS: The internal thoracic artery graft and use of the operating microscope confer a superior clinical advantage over the saphenous vein graft throughout a 20-year follow-up period. The advantage of an internal thoracic artery graft does not decrease with time, suggesting that the choice of conduit at the initial operation is more important clinically than progression of coronary artery disease. PMID- 7798500 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 5: training in nuclear cardiology. PMID- 7798501 TI - Relation of saphenous vein graft obstruction to serum cholesterol levels. AB - OBJECTIVES: To determine the potential of lipid-lowering therapy to reduce saphenous vein graft obstruction, we retrospectively studied the association between graft obstruction and serum cholesterol levels. BACKGROUND: Atherosclerosis is the major cause of vein graft obstruction. Approximately 50% of grafts are occluded by 10 years after operation. It remains to be established whether lipid control affects long-term graft survival. METHODS: We carried out a retrospective review of all 284 patients who had undergone coronary artery bypass graft surgery at Juntendo University Hospital between 1976 and 1991 and met the following additional criteria: at least one saphenous vein graft, repeat coronary arteriography at some point after coronary artery bypass graft surgery and a serum cholesterol level > or = 200 mg/dl before operation. Saphenous vein graft obstruction rates were compared among three groups classified by serum cholesterol levels at follow-up arteriography: group I < 200 mg/dl; group II 200 to 239 mg/dl; group III > or = 240 mg/dl. A vein graft was considered obstructed if it was narrowed by > or = 70%. RESULTS: In group I, 88% of grafts were not obstructed 7 years after operation. The respective rates were 61% in group II and 57% in group III (p < 0.005). This relation was true for vein grafts to the left anterior descending and other coronary arteries. CONCLUSIONS: Lower serum cholesterol levels are associated with lower rates of vein graft obstruction for up to 7 years. This suggests that cholesterol-lowering therapy may improve long term saphenous vein graft survival after coronary artery bypass surgery. PMID- 7798502 TI - Right coronary artery stenosis: an independent predictor of atrial fibrillation after coronary artery bypass surgery. AB - OBJECTIVES: This study attempted to determine the importance of severe proximal right coronary artery disease as a predictor of atrial fibrillation in patients after coronary artery bypass surgery. BACKGROUND: Studies in patients undergoing noncardiac surgery have suggested that ischemia in the right coronary artery distribution is associated with a high incidence of atrial fibrillation. However, the importance of right coronary artery disease as a predictor of atrial fibrillation after bypass surgery is unknown. METHODS: The occurrence of sustained postoperative atrial fibrillation was studied prospectively in 168 consecutive patients undergoing coronary artery bypass grafting. Patients were followed up postoperatively until discharge. Severe right coronary artery stenosis was defined as > or = 70% lumen narrowing. RESULTS: Of 104 patients with proximal or mid right coronary artery stenosis, 45 (43%) had atrial fibrillation postoperatively compared with 12 (19%) of the 64 patients without significant right coronary disease (p = 0.001). Univariate predictors of atrial fibrillation included right coronary artery stenosis (p = 0.001), advancing age (p = 0.0001) and lack of beta-adrenergic blocking agent therapy after bypass surgery (p = 0.0004). Multivariate adjusted risk of developing atrial fibrillation after bypass surgery increased with the presence of severe right coronary artery disease (odds ratio 3.69, 95% confidence interval [CI] 1.61 to 8.48), advancing age (odds ratio 2.24/10 years, CI 1.48 to 3.41) and male gender (odds ratio 2.36, CI 1.01 to 5.49). The use of beta-blockers postoperatively was associated with a protective effect (odds ratio 0.4, CI 0.17 to 0.80). CONCLUSIONS: The presence of severe right coronary artery stenosis is an independent and powerful predictor of atrial fibrillation after coronary artery bypass surgery. In association with age, gender and postoperative beta-blocker therapy, these variables can be used to identify patients at increased risk for developing this arrhythmia. PMID- 7798503 TI - Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction. AB - OBJECTIVES: This prospective study investigated the behavior of thrombin generation and activity during thrombolysis and concomitant heparin administration. BACKGROUND: It has been shown that during thrombolytic therapy there is an increase in thrombin generation and activity. Increased thrombin activity is suppressed by concomitant intravenous heparin, but it is unknown whether thrombin generation is also affected. METHODS: Thrombin generation was assessed by measuring prothrombin fragment 1 + 2 and thrombin-antithrombin complex plasma levels and thrombin activity by measuring fibrinopeptide A plasma levels. Serial blood samples were obtained before and at 90 min and 24 and 48 h after the administration of streptokinase (15 patients), recombinant tissue-type plasminogen activator (15 patients) or anistreplase (13 patients). An intravenous bolus of heparin (5,000 IU) was administered before the start of thrombolytic therapy, followed by an infusion of 1,000 U/h to maintain an activated partial thromboplastin time > 1.5 times baseline. RESULTS: During thrombolytic and concomitant heparin therapy, there was an increase in the plasma levels of prothrombin fragment 1 + 2 (baseline 1.08 vs. 2.73 nmol/liter, p < 0.001) and thrombin-antithrombin complex (baseline 6.5 vs. 17.1 micrograms/ml, p < 0.01) at 90 min, whereas no change was observed in fibrinopeptide A at 90 min (baseline 2.8 vs. 3.0 nmol/liter, p = NS). CONCLUSIONS: During thrombolytic therapy with both fibrin-specific and non-fibrin-specific drugs, there is an increase in thrombin generation despite concomitant administration of intravenous heparin. PMID- 7798504 TI - Rest-redistribution thallium-201 scintigraphy to determine myocardial viability early after myocardial infarction. AB - OBJECTIVES: This study attempted to determine the utility of early rest redistribution thallium-201 imaging in detecting residual myocardial viability after myocardial infarction. BACKGROUND: The early detection of myocardial viability after myocardial infarction would have clinical relevance. METHODS: Thirty-one patients with acute myocardial infarction had early (mean [+/- SD] 2 +/- 1 day) rest-redistribution thallium-201 imaging followed by radionuclide and coronary angiography. Late studies included stress-redistribution-reinjection thallium-201 imaging or radionuclide angiography, or both. Viability was defined by the rest thallium-201 scan as an initial mild rest defect or any defect that demonstrated redistribution. RESULTS: Group 1 (n = 15) was predicted to have viable and Group 2 (n = 16) nonviable myocardium in the infarct zone. Group 1 patients were more likely to have a patent infarct-related artery (15 of 15 vs. 10 of 16, p < 0.03), higher initial ejection fraction (61 +/- 12% vs. 53 +/- 9%, p < 0.05), higher infarct wall motion score (p < 0.0001) and fewer abnormal thallium-201 segments (p < 0.0001). On follow-up studies, ejection fraction improved in Group 1 (from 57 +/- 13% to 66 +/- 10%, p < 0.05, n = 9) and deteriorated in Group 2 (from 53 +/- 10% to 46 +/- 8%, p < 0.05, n = 13). On late stress testing with thallium-201 reinjection, Group 1 patients had fewer abnormal segments (p < 0.03) and higher infarct zone counts during exercise (p < 0.05) and after reinjection (p < 0.05) than Group 2 patients. CONCLUSIONS: If confirmed by larger studies, early rest-redistribution thallium-201 imaging may be a useful technique for identifying residual viability after myocardial infarction. PMID- 7798505 TI - Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy. AB - OBJECTIVES: This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction. BACKGROUND: Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown. METHODS: To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later. RESULTS: At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo). CONCLUSIONS: Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion. PMID- 7798506 TI - Coronary reactivity to nitroglycerin: intravascular ultrasound evidence for the importance of plaque distribution. AB - OBJECTIVES: This study was designed to assess the extent and timing of vasodilation after intracoronary administration of nitroglycerin using intravascular ultrasound. We also sought to relate the magnitude of nitroglycerin induced dilation to the distribution of atherosclerotic plaque. BACKGROUND: Although previous angiographic studies have shown that nitroglycerin can dilate both normal and stenotic coronary arteries, it remains uncertain whether atherosclerotic vessels can respond to nitroglycerin to the same extent as normal arteries in the clinical setting. METHODS: We analyzed a total of 48 segments from 48 patients by means of a multielement 3.5F to 5.5F 20-MHz intravascular ultrasound system before and after intracoronary administration of nitroglycerin (250 micrograms). Videotaped images were digitized, and the lumen cross-sectional area was measured with an electronic cursor. In noncircumferential lesions, the perimeters of the normal and diseased portions were measured separately to compare the reactivity to nitroglycerin in each portion. RESULTS: Of 48 sites examined 14 were normal by ultrasound, and 34 revealed atherosclerotic lesions. In the 14 normal segments nitroglycerin produced a large increase in cross sectional area (31 +/- 16% [mean +/- SD]) within 60 s after injection. In the 34 atherosclerotic segments, nitroglycerin-induced dilation was impaired, and the cross-sectional area increased only 12 +/- 8% (p < 0.01). In 15 of 34 atherosclerotic segments, a noncircumferential lesion was identified, and the cross-sectional area after nitroglycerin increased an average of 17 +/- 6%. In the remaining 19 sites, circumferential disease was present, and the cross sectional area increased by only 8 +/- 7% (p < 0.05 vs. normal or noncircumferential atherosclerotic segments). In noncircumferential lesions, the increase in the perimeter of the normal portion of the wall was significantly greater (14 +/- 6%) than the increase in the diseased portion (5 +/- 3%, p < 0.05). CONCLUSIONS: These data indicate that vasoreactivity after nitroglycerin administration is reduced in segments with atherosclerosis by ultrasound. We suggest that nitroglycerin-induced vasodilation at the stenotic segments can be produced primarily by expansion of the nondiseased portion of the vessel wall. PMID- 7798507 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 6: training in specialized electrophysiology, cardiac pacing and arrhythmia management. PMID- 7798508 TI - Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine. The TIBBS Investigators. AB - OBJECTIVES: We compared the effects of bisoprolol on transient myocardial ischemia with those of nifedipine in patients with chronic stable angina. BACKGROUND: Both beta-adrenergic blocking agents and calcium antagonists reduce transient ischemic episodes, but comparisons of these agents have been made in only a few larger studies. METHODS: The Total Ischemic Burden Bisoprolol Study (TIBBS) was a randomized double-blind controlled study with two parallel groups; 330 patients from 30 centers in seven European countries with stable angina pectoris, a positive exercise test and more than two transient ischemic episodes during 48 h of Holter monitoring (central evaluation) were included. Of these patients 161 were randomized to receive bisoprolol and 169 to receive nifedipine slow release. There were two treatment phases of 4 weeks each, with 48-h Holter monitoring after each phase. During phase 1, patients received either 10 mg of bisoprolol daily or 2 x 20 mg of nifedipine slow release. During phase 2, they received either 20 mg of bisoprolol daily or 2 x 40 mg of nifedipine slow release. RESULTS: In phase 1 of the trial, 4 weeks of bisoprolol therapy (10 mg daily) reduced the mean [+/- SD] number of transient ischemic episodes from 8.1 +/- 0.6 to 3.2 +/- 0.4/48 h. Nifedipine (2 x 20 mg) reduced transient ischemic episodes from 8.3 +/- 0.5 to 5.9 +/- 0.4/48 h. Total duration of ischemia was reduced from 99.3 +/- 10.1 to 31.9 +/- 5.5 min/48 h with bisoprolol and from 101 +/- 9.1 to 72.6 +/- 8.1 min/48 h with nifedipine. Reductions were statistically significant for both drugs; the difference between bisoprolol and nifedipine was also significant (p < 0.0001). Bisoprolol reduced the heart rate at onset of episodes by 13.7 +/- 1.4 beats/min from a baseline value of 99.5 +/- 1.2 beats/min (p < 0.001). Heart rate was unchanged with nifedipine. Bisoprolol had significantly higher responder rates than nifedipine. Doubling of the dose in phase 2 of the trial had small additive effects. Only bisoprolol showed a marked circadian effect by reducing the morning peak of transient ischemic episodes (by 68% at peak time, 8:00 to 8:59 AM). CONCLUSIONS: Both bisoprolol and nifedipine reduced the number and duration of transient ischemic episodes in patients with chronic stable angina. Bisoprolol was significantly more effective than nifedipine in both doses tested and reduced the morning peak of ischemic activity. PMID- 7798509 TI - Correlation between cardiac involvement and CTG trinucleotide repeat length in myotonic dystrophy. AB - OBJECTIVES: Because sudden death due to complete atrioventricular (AV) block or ventricular arrhythmias is the most dramatic event in myotonic dystrophy, we assessed the relation of cardiac disease to cytosine-thymine-guanine (CTG) triplet mutation in adults affected with myotonic dystrophy. BACKGROUND: The myotonic dystrophy mutation, identified as an unstable deoxyribonucleic acid (DNA) sequence (CTG) prone to increase the number of trinucleotide repeats, produces clinical manifestations of the disease in skeletal muscle, the heart and many organ systems. METHODS: Forty-two adult patients underwent electrocardiography and echocardiography; in addition, signal-averaging electrocardiography was performed in 22, and 24-h Holter monitoring was recorded in 32. The diagnosis was established by neurologic examination, electromyography, muscle biopsy and DNA analysis. The patients were then classified into three subgroups on the basis of the number of CTG trinucleotide repeat expansions: E1 = 18 patients with 0 to 500 CTG repeats; E2 = 12 patients with up to 1,000 repeats; E3 + E4 = 10 patients with up to 1,500 repeats and 2 patients with > 1,500 repeats. RESULTS: The incidence of normal electrocardiographic (ECG) results was found to be significantly different in the three subgroups (55%, 50%, 17% in E1, E2, E3, + E4, respectively, p = 0.04), with the highest values in the group with fewer repeat expansions. The incidence of complete left bundle branch block was also significantly different among the groups (5% in E1, 0% in E2, 42% in E3 + E4 p = 0.01) and was directly correlated with the size of the expansion. A time domain analysis of the signal-averaged ECG obtained in 12 patients in E1, 4 in E2, 5 in E3 and 1 in E4 showed that abnormal ventricular late potentials were directly correlated with CTG expansion (33% in E1, 75% in E2, 83% in E3 + E4, p = 0.05). Moreover, the incidence of ventricular couplets or triplets showed a positive correlation with size of CTG expansion (0 in E1, 0 in E2, 29% in E3 + E4, chi square 0.02). CONCLUSIONS: Our findings suggest that the involvement of specialized cardiac tissue, accounting for severe AV and intraventricular conduction defects, is related to CTG repeat length. In addition, the presence of abnormal late potentials directly correlates to CTG expansion. Abnormal late potentials, caused by slowed and fragmented conduction through damaged areas of myocardium, represent a substrate for malignant reentrant ventricular arrhythmias. In the future, therefore, molecular analysis of DNA should identify patients with cardiac disease at high risk for development of AV block or lethal ventricular arrhythmias. PMID- 7798510 TI - Angiotensin II inhibits the forearm vascular response to increased arterial pressure in humans. AB - OBJECTIVES: This study tested the hypothesis that angiotensin II may inhibit the forearm vascular resistance response to an increase in arterial pressure in normal humans. BACKGROUND: Angiotensin II inhibits baroreflex-mediated reductions in heart rate and peripheral sympathetic activity during increases in arterial pressure in experimental animals. If present in humans, such effects could contribute to the pathophysiologic role of angiotensin II in hypertension and heart failure. METHODS: Two investigations were performed. In the first, forearm vascular resistance responses were compared during equipressor infusions of angiotensin II and phenylephrine. In the second, heart rate, forearm vascular resistance and systemic venous norepinephrine spillover responses were compared during head-down tilt and head-down tilt plus phenylephrine with concomitant angiotensin II or vehicle infusions. RESULTS: In the first study, forearm vascular resistance increased from 44 +/- 12 (mean +/- SD) to 54 +/- 13 U (p < 0.05) during angiotensin II but did not change during phenylephrine infusions (39 +/- 8.5 to 40 +/- 14 U) that increased mean arterial pressure comparably (88 +/- 9.8 to 103 +/- 14 mm Hg during angiotensin II, p < 0.001; 91 +/- 7.6 to 104 +/- 9.2 mm Hg during phenylephrine, p < 0.001). In the second study, the decrease in heart rate and forearm vascular resistance during the combination of head-down tilt and phenylephrine were both attenuated during concomitant angiotensin II compared with vehicle infusions: delta HR/delta MAP = -2.2 beats/min per mm Hg during vehicle and -0.87 beats/min per mm Hg during angiotensin II (p = 0.07); delta FVR/delta MAP = -2.8 U/mm Hg during vehicle and -0.19 U/mm Hg during angiotensin II (p = 0.01), where delta HR = change in heart rate; delta MAP = change in mean arterial pressure; and delta FVR = change in forearm vascular resistance. Norepinephrine spillover declined during vehicle infusions (612 +/- 367 to 418 +/- 196 ng/min, p < 0.05) but not during angiotensin II infusions despite a greater increase in mean arterial pressure when the subpressor angiotensin II was combined with head-down tilt and phenylephrine (6.0 +/- 7.0 mm Hg during vehicle; 14 +/- 9.4 mm Hg during angiotensin II, p < 0.01). CONCLUSIONS: Both pressor and nonpressor infusions of angiotensin II immediately inhibit the forearm vascular response to mild baroreflex loading in normal humans. If present over the long term, such effects could contribute to inappropriate peripheral resistance in diseases such as hypertension and congestive heart failure. PMID- 7798511 TI - Muscular and cardiac adenosine-induced pain is mediated by A1 receptors. AB - OBJECTIVES: This study attempted to establish whether bamiphylline, a selective antagonist of A1 adenosine receptors, prevents the algogenic effects of adenosine in humans. BACKGROUND: Experimental findings indicate that the sympathoexcitatory response elicited by adenosine is mediated by A1 receptors. METHODS: An intrailiac infusion of increasing doses (from 125 to 2,000 micrograms/min) of adenosine was given to 20 patients. Adenosine infusion was then repeated after intrailiac infusion of either bamiphylline or saline solution. In 14 other patients with angina, increasing doses of adenosine (from 108 to 1,728 micrograms/min) were infused into the left coronary artery. Adenosine infusion was then repeated after the intravenous infusion of either bamiphylline or placebo. Coronary blood flow velocity was monitored by a Doppler catheter. Data relative to pain severity are expressed as median and all other data as mean value +/- 1 SD. RESULTS: Bamiphylline prolonged the time to pain onset caused by the intrailiac adenosine infusion from 444 +/- 96 to 749 +/- 120 s (p < 0.001) and reduced pain severity from 45 to 24 mm (p < 0.01). After placebo infusion, the time to pain onset and pain severity were similar to that of baseline (428 +/ 112 vs. 430 +/- 104 s, p = 0.87 and 44 vs. 43 mm, p = 0.67, respectively). Bamiphylline prolonged the time to pain onset caused by intracoronary adenosine infusion from 519 +/- 128 to 603 +/- 146 s (p < 0.01) and reduced pain severity from 58 to 28 mm (p < 0.02). After placebo infusion, the time to pain onset and pain severity were similar to that at baseline (542 +/- 87 vs. 551 +/- 79 s, p = 0.14 and 55 vs. 50 mm, p = 0.61). Maximal coronary blood flow velocities before and after bamiphylline administration were similar (47 +/- 22 vs. 49 +/- 24 cm/s, p = 0.36) as well as before and after placebo administrtion (40 +/- 20 vs. 41 +/- 20 cm/s, p = 0.07). CONCLUSIONS: Bamiphylline reduces adenosine-induced muscular and cardiac pain but does not affect adenosine-induced coronary vasodilation. These findings indicate that at the dose used in this study, bamiphylline does not detectably block vascular A2-receptor-mediated adenosine effects in humans, which suggests that the muscular and cardiac algogenic effects of adenosine are mediated mainly by A1 receptors. PMID- 7798513 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 7: training in cardiovascular research. AB - It is vital to the future intellectual health of cardiovascular medicine and the welfare of patients with cardiovascular disease that all future cardiologists be familiar with the principles and tools of research. Training in research requires the intense involvement of productive and established investigators. Those trainees preparing for a career in investigative cardiology require a carefully developed but flexible educational plan that will permit them to be successful in their research careers over an extended period. PMID- 7798512 TI - Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization. AB - OBJECTIVES: The short- and long-term effectiveness of transmyocardial laser revascularization was evaluated in the setting of an acute myocardial infarction. BACKGROUND: Theoretically, transmyocardial laser revascularization allows direct perfusion of the ischemic area as ventricular blood flows through the channels to the myocardium. METHODS: Infarcts were created by coronary occlusion in 30 sheep. Eighteen of these sheep were studied to assess short-term efficacy. The infarct was reperfused after 1 h by either removing the occlusion or by laser drilling using a high power carbon dioxide laser. The occlusions were left in place for the control group. To monitor regional recovery, percent systolic shortening was measured. To evaluate long-term effectiveness, 12 additional sheep underwent creation of an infarct. Six were treated with the laser, and six were untreated. The animals were restudied 30 days later. RESULTS: In the short-term experiment, the control and reperfusion groups exhibited no recovery of regional contractility. The laser group demonstrated improvement throughout the recovery period. There was a significant difference in the area of necrosis within the same area at risk (reperfusion group 44 +/- 6% and control group 39 +/- 5% vs. laser group 6 +/- 2%). After 30 days, none of the control animals showed evidence of contraction in the infarct, whereas the laser-treated animals did. Histologic analysis of the laser-treated infarcts revealed patent channels surrounded by viable myocardium. The control-group infarcts were necrotic and scarred. CONCLUSIONS: On the basis of both short- and long-term improved contractility, as well as diminished necrosis in the area at risk, these results indicate that transmyocardial laser revascularization may be an alternative method of treating ischemic heart disease. PMID- 7798514 TI - Doppler evaluation of severity of mitral regurgitation: relation to pulmonary venous blood flow patterns in an animal study. AB - OBJECTIVES: This study examined the influence of regurgitant volume on pulmonary venous blood flow patterns in an animal model with quantifiable mitral regurgitation. BACKGROUND: Systolic pulmonary venous blood flow is influenced by atrial filling and compliance and ventricular output and by the presence of mitral regurgitation. The quantitative severity of the regurgitant volume itself is difficult to judge in clinical examinations. METHODS: Six sheep with chronic mitral regurgitation produced by previous operation to create chordal damage were examined. At reoperation the heart was exposed and epicardial echocardiography performed. Pulmonary venous blood flow waveforms were recorded by pulsed Doppler under color flow Doppler guidance using a Vingmed 750 scanner. The pulmonary venous systolic inflow to the left atrium was expressed as a fraction of the total inflow velocity time integral. Flows across the aortic and mitral valves were recorded by electromagnetic flowmeters balanced against each other. Pressures in the left ventricle and left atrium were measured directly with high fidelity manometer-tipped catheters. Preload and afterload were systematically manipulated, resulting in 24 stable hemodynamic states. RESULTS: Simple logarithmic correlation between the regurgitant volume and size of a positive or negative pulmonary venous inflow velocity time integral during systole was good (r = -0.841). By stepwise linear regression analysis with pulmonary venous negative systolic velocity time integral as a dependent variable compared with the regurgitant volume, fractional shortening, left atrial v wave size, systemic vascular resistance and left ventricular systolic pressure, only contributions from v wave size and regurgitant volume (r = 0.80) reached statistical significance in determining pulmonary venous negative systolic flow. CONCLUSIONS: Evaluation of systolic pulmonary venous blood flow velocity time integral can give valuable information helpful for estimating the regurgitant volume secondary to mitral regurgitation. PMID- 7798516 TI - Academic subspecialties at the crossroad. PMID- 7798515 TI - Potentiation of endogenous nitric oxide with superoxide dismutase inhibits platelet-mediated thrombosis in injured and stenotic arteries. AB - OBJECTIVES: We tested the hypothesis that dismutation of superoxide anion increases endogenous levels of nitric oxide, resulting in inhibition of cyclic variations in blood flow in arteries that are injured and stenotic. BACKGROUND: Platelet adhesion and aggregation leading to cyclic flow variations might result, in part, from generation of superoxide anion that can deplete endogenously produced nitric oxide. METHODS: Spontaneous cyclic flow variations, monitored with a proximal Doppler probe, were induced in the carotid artery of anesthetized rabbits by clamping the vessel with forceps and placing a high grade stenosis at the site of injury. Bovine copper/zinc superoxide dismutase (12 mg/kg body weight, n = 5), a synthetic low molecular weight mimetic (12 mg/kg, n = 8) or buffer vehicle (n = 8) was administered intravenously as divided boluses over 45 min, and the frequency of cyclic flow variations was monitored for 4 h. RESULTS: Cyclic flow variations remained stable for 4 h in vehicle-treated animals (15 +/- 1 [mean +/- SEM]/30 min at baseline and 16 +/- 1/30 min after 4 h, n = 8) but exhibited a marked and persistent reduction in animals given copper/zinc superoxide dismutase (from 14 +/- 1/30 min at baseline to 4 +/- 1/30 min after 4 h) or the mimetic (from 15 +/- 1/30 min at baseline to 3 +/- 1/30 min after 4 h, p < 0.005). They were restored in three of four mimetic-treated animals during infusion of NG-monomethyl- L-arginine (100 mg/kg), an inhibitor of nitric oxide production. In addition, levels of cyclic guanosine 5'-monophosphate in platelets were elevated after administration of the mimetic (from 2.4 +/- 0.5 fmol/10(6) platelets at baseline to 4.9 +/- 0.6 fmol/10(6) platelets 45 min after the mimetic, p < 0.03, n = 6), whereas mean arterial blood pressure was decreased and flow velocity in the carotid artery was increased consistent with mediation of the effect on cyclic flow variations by increased endogenous nitric oxide. CONCLUSIONS: Dismutation of superoxide anion appears to attenuate platelet thrombus formation at a site of vessel injury by potentiation of endogenously produced nitric oxide. This approach may have utility to inhibit platelet-rich thrombosis in injured and stenotic arteries where production of superoxide anion is increased. PMID- 7798517 TI - President's page: work force issues in cardiology. PMID- 7798518 TI - Exercise echocardiography. PMID- 7798520 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 9: training in the care of adult patients with congenital heart disease. PMID- 7798519 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 8: training in heart failure and transplantation. PMID- 7798521 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 10: training in preventive cardiovascular medicine. PMID- 7798522 TI - Advance directives: do they work? AB - Advance directives have been widely endorsed, and empiric work has taken place that can aid clinicians in the appropriate use of validated documents. This report reviews philosophic and methodologic issues and offers practical illustrations. Despite the evidence that advance directives can work, there are serious barriers to their actual use. Therefore, these barriers are evaluated and potential solutions suggested. PMID- 7798523 TI - Modulation of atrioventricular conduction by ablation of the "slow" atrioventricular node pathway in patients with drug-refractory atrial fibrillation or flutter. AB - OBJECTIVES: We hypothesized that modulation of atrioventricular (AV) node conduction, allowing a reduction in ventricular rate during atrial fibrillation or flutter without affecting AV conduction during sinus rhythm, might be achieved through ablation of the "slow" AV node pathway. BACKGROUND: In patients with atrial fibrillation or flutter not amenable to a direct atrial approach, ablation of the His bundle is performed to induce complete AV block. This procedure causes pacemaker dependence. METHODS: Fourteen patients with drug-refractory paroxysmal atrial flutter or fibrillation underwent ablation of the slow AV node pathway. Radiofrequency current was delivered in six patients during sinus rhythm, in six during atrial flutter and in two during atrial fibrillation. RESULTS: The anterograde effective refractory period of the AV node was prolonged from 270 +/- 50 (mean +/- SD) to 390 +/- 87 ms (p = 0.005) and the Wenckebach cycle from 346 +/- 33 to 458 +/- 75 ms (p = 0.004) in six patients during sinus rhythm. Mean AV ratio increased from 1.6 +/- 0.5 to 3.0 +/- 0.6 (p = 0.02) in six patients with atrial flutter. Mean ventricular rate decreased from 157 +/- 38 to 67 +/- 10 beats/min in two patients with atrial fibrillation. Complete AV block was induced in two patients (transient in one, permanent in one). During a follow-up period of 5.8 +/- 3.5 months, 11 patients experienced a recurrence of atrial fibrillation at 60 to 95 beats/min. No patient had progression to any degree of AV block. CONCLUSIONS: Ablation of the slow AV node pathway allows reduction of ventricular rate during atrial fibrillation or flutter while maintaining intact AV conduction during sinus rhythm. Modulation of AV node conduction is effective in most patients as an alternative to His bundle ablation for control of ventricular rate in paroxysmal atrial fibrillation or flutter. PMID- 7798524 TI - Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 1: training in clinical cardiology. PMID- 7798525 TI - Characterization of return cycle responses predictive of successful pacing mediated termination of ventricular tachycardia. AB - OBJECTIVES: The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia. BACKGROUND: Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied. METHODS: Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared. RESULTS: Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r2 = 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit. CONCLUSIONS: The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms. PMID- 7798526 TI - Long-term outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without structural heart disease. AB - OBJECTIVES: This study attempted to determine the long-term outcome of verapamil sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease. BACKGROUND: Several types of idiopathic ventricular tachycardia have been reported, and their clinical, electrophysiologic and electropharmacologic characteristics are different. It is possible that the prognosis of each type of ventricular tachycardia might also be different. METHODS: We studied mortality and morbidity in 37 consecutive patients (27 male, 10 female; mean [+/- SD] age 33 +/- 14 years) with verapamil-sensitive sustained left ventricular tachycardia who had no apparent structural heart disease. Patients were followed up for 1 to 13 years (mean 5.8). Verapamil repeatedly terminated ventricular tachycardia in all patients. Ventricular tachycardia originated from the inferior and inferoseptal regions of the left ventricle in 33 patients and the superior and superioseptal regions in 4. Severity of ventricular tachycardia was classified according to the extent to which symptoms limited daily activities. Ventricular tachycardia was mild (minimal limitation) in 14 patients, moderate (some limitation) in 17 and severe (severe limitation) in 6. RESULTS: Fourteen patients with mild ventricular tachycardia were followed up without any drug therapy, and the ventricular tachycardia remained mild in all patients. Antiarrhythmic therapy was initiated empirically in the 23 patients with moderate and severe ventricular tachycardia (verapamil in 20, propranolol in 2, digoxin in 1). Moderate ventricular tachycardia became mild ventricular tachycardia after drug therapy in all patients, but the six patients with severe ventricular tachycardia showed no improvement. The six patients with severe ventricular tachycardia had nonpharmacologic therapy (cryosurgery in one, catheter ablation in four, antitachycardia pacing device in one). During the follow-up period, all patients remained alive except for one who died suddenly after implantation of an antitachycardia pacing device. CONCLUSIONS: 1) The long term prognosis of verapamil-sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease is good. 2) Verapamil is the drug of choice for alleviating symptoms, but nonpharmacologic therapy is necessary in some patients. PMID- 7798527 TI - A new form of long QT syndrome associated with syndactyly. AB - OBJECTIVES: The purpose of this study was to characterize a possible association between long QT syndrome and syndactyly. BACKGROUND: Long QT syndrome causes syncope and sudden death from ventricular arrhythmias. Syndactyly is a developmental disorder that causes webbing of the hands and feet. Both disorders can be inherited as isolated, autosomal dominant traits, but an association between them has not been established. METHODS: We identified three children with long QT syndrome, atrioventricular (AV) block and simple syndactyly. Phenotypic and laboratory data were obtained from families, attending physicians and medical records. RESULTS: All patients had bilateral cutaneous syndactyly and were diagnosed with long QT syndrome within the 1st 2 years of life. Structural heart disease, particularly a patent ductus arteriosus, was present in all three patients. Analysis of electrocardiograms showed marked prolongation of the QT intervals with rate-corrected QT intervals of 633, 628 and 680 ms, respectively. Transient AV block was also noted. Two of the three children died suddenly despite treatment with beta-adrenergic blocking agents and permanent pacing. CONCLUSIONS: We postulate that these children have a new form of long QT syndrome associated with syndactyly and a high risk of sudden death. The association of syndactyly with long QT syndrome may provide insight into the mechanisms underlying both disorders. Patients with syndactyly should be evaluated for the presence of long QT syndrome, and if it is found, aggressive treatment may be warranted. PMID- 7798528 TI - Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo. AB - OBJECTIVES: This study assessed the efficacy of oral etilefrine (10 mg three times a day) in preventing a positive response to head-up tilt testing. BACKGROUND: Previous reports have suggested that oral etilefrine can be effective either in preventing a positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled. METHODS: This was a randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and a baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and a third test was performed. RESULTS: Head up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: A positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05). CONCLUSIONS: Oral etilefrine (10 mg three times a day) was not superior to placebo in preventing a positive response to head-up tilt testing. Despite a low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope. PMID- 7798529 TI - Characterization of subcutaneous microvascular blood flow during tilt table induced neurally mediated syncope. AB - OBJECTIVES: This study aimed to characterize subcutaneous blood flow changes during neurally mediated syncope and to determine whether microvasculature oscillation (vasomotion) is characteristically altered in conjunction with syncopal events. BACKGROUND: Marked pallor is commonly associated with neurally mediated syncope. However, little attention has been paid to the evaluation of subcutaneous blood flow and vasomotion in this setting. METHODS: This study utilized laser Doppler flowmetry to assess changes in subcutaneous microvascular blood flow during head-up tilt table testing in 13 patients with syncope and 6 control subjects. Blood flow and vasomotion frequency were measured continuously before, during and after completion of 80 degrees head-up tilt testing (< or = 25 min duration). RESULTS: Among the 13 patients with syncope, tilt testing reproduced syncopal symptoms in 9 (tilt-positive group) but not in 4 (tilt negative group). None of the six control subjects developed symptoms during testing. Baseline mean subcutaneous blood flow did not differ significantly among the three groups. However, during upright tilt, blood flow gradually diminished in the tilt-positive group, reaching a nadir of 0.8 +/- 0.33 ml/min per 100 g of tissue (mean +/- SD), but remained relatively constant in the tilt-negative group and control subjects. The difference in mean blood flow response to tilt was statistically significant when the tilt-positive group was compared with either the tilt-negative group or control subjects (p < 0.001). Similarly, baseline blood flow oscillation frequency did not differ significantly in the three subgroups (tilt-positive group 0.2 +/- 0.11 Hz; tilt-negative group 0.2 +/- 0.02 Hz; control subjects 0.2 +/- 0.11 Hz). Subsequently, during tilt testing only the tilt-positive group exhibited increased oscillation frequency; oscillation frequency remained essentially constant throughout the tilt test in the tilt negative group and control subjects (p < 0.001, tilt-positive group vs. either the tilt-negative group or control subjects). CONCLUSIONS: These findings document an expected diminution of subcutaneous blood flow in association with neurally mediated syncope and indicate that characteristic changes in microvasculature oscillation frequency occur in conjunction with syncopal symptoms. To the extent that microvasculature vasomotion is influenced by neural control, the changes in vasomotion frequency are consistent with relative diminution of peripheral sympathetic neural influence during neurally mediated syncopal episodes. PMID- 7798530 TI - Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. AB - OBJECTIVES: This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND: Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS: Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS: Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS: Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease. PMID- 7798532 TI - Influence of left ventricular hypertrophy on left ventricular function during dynamic exercise in the presence or absence of coronary artery disease. AB - OBJECTIVES: We investigated the influence of left ventricular hypertrophy in the presence or absence of coronary artery disease on hemodynamic characteristics during exercise in subjects without previous myocardial infarction. BACKGROUND: Left ventricular hypertrophy has been found to increase the vulnerability of the myocardium to the development of ischemia. However, the independent influences of left ventricular hypertrophy and coronary artery disease have not been assessed in humans. METHODS: Symptom-limited supine leg exercise tests were performed by 78 patients. They were classified into the following subgroups: no coronary artery disease or left ventricular hypertrophy (group I, n = 30), left ventricular hypertrophy only (group II, n = 12), coronary artery disease only (group III, n = 20) and both left ventricular hypertrophy and coronary artery disease (group IV, n = 16). Mean left ventricular mass index was 105, 158, 109 and 159 g/m2 in groups I to IV, respectively. RESULTS: Pulmonary artery wedge pressure increased from 6 +/- 3 (mean +/- SD) mm Hg at rest to 10 +/- 5 mm Hg at peak exercise in group I, from 8 +/- 2 to 18 +/- 8 mm Hg in group II (p < 0.05 vs. group I), from 6 +/- 3 to 23 +/- 6 mm Hg in group III (p < 0.01 vs. group I) and from 8 +/- 4 to 30 +/- 7 mm Hg in group IV (p < 0.01 vs. group I; p < 0.01 vs. group II; p < 0.05 vs. group III). Multiple regression analysis showed that the number of diseased coronary vessels and left ventricular mass index were independent predictors of peak pulmonary artery wedge pressure (F = 59.2 and 19.1, respectively; multiple correlation coefficient r = 0.74, p < 0.0001). CONCLUSIONS: Left ventricular hypertrophy and coronary artery disease independently increased left ventricular filling pressure during supine leg exercise. Severe left ventricular dysfunction was induced by exercise when both conditions were present. PMID- 7798531 TI - Association of carotid atherosclerosis and left ventricular hypertrophy. AB - OBJECTIVES: This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy. BACKGROUND: Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown. METHODS: Four hundred eighty-six (277 normotensive and 209 untreated hypertensive) adults, free of clinical evidence of cardiovascular disease, were studied prospectively with echocardiography to determine left ventricular mass and carotid ultrasound to detect atherosclerosis and to measure common carotid artery dimensions. RESULTS: Carotid atherosclerosis was present in 16% of normotensive and 23% of hypertensive participants (p < 0.05) and was associated with older age, higher systolic and pulse pressures and larger left ventricular mass index ([mean +/- SD] 91 +/- 19 vs. 82 +/- 18 g/m2, p < 0.0001). The difference in mass persisted after adjustment for baseline differences in age and blood pressure. Subjects with left ventricular hypertrophy were twice as likely to have carotid atheromas (35% vs. 18%, p < 0.01). Logistic regression analyses, including standard risk factors, indicated that only age and left ventricular mass index independently predicted the presence of carotid plaque, both in the entire study group and when normotensive and hypertensive subjects were considered separately. CONCLUSIONS: We believe that the present study provides the first evidence that higher left ventricular mass as detected by echocardiography is associated with the presence of carotid plaque. The association between cardiac hypertrophy and systemic atherosclerosis may contribute to the pathogenesis of the high incidence of vascular events that is well documented in patients with left ventricular hypertrophy. PMID- 7798533 TI - Adenosine pharmacologic stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis. Diagnostic efficacy and comparison of clinical, hemodynamic and electrocardiographic variables with 100 age-matched control subjects. AB - OBJECTIVES: This study assessed the safety and diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy for the detection of coronary artery disease using single-photon emission computed tomography (SPECT) in patients with significant aortic stenosis. BACKGROUND: Exercise cardiac stress testing in patients with significant aortic stenosis is generally avoided because of concerns for safety. In addition, those studies that have analyzed the utility of exercise testing both with and without myocardial thallium-201 scintigraphy for the diagnosis of coronary artery disease have yielded low specificity. Currently, no safe and accurate means exists to noninvasively assess the presence, extent and severity of coronary artery disease in patients with significant aortic stenosis. METHODS: The study included 35 patients with moderate to severe aortic stenosis (mean [+/- SD] aortic valve area 0.84 +/- 0.16 cm2, range 0.5 to 1.2; mean maximal instantaneous aortic valve gradient 44.4 +/- 15.9 mm Hg, range 20 to 84). All patients underwent a 6-min adenosine infusion (140 micrograms/kg body weight per min) protocol and either separate acquisition rest thallium-201/stress technetium-99m sestamibi or stress and 4-h redistribution thallium-201 SPECT: Visual 20-segment SPECT analysis used a standard five-point scoring system from 0 (normal tracer uptake) to 4 (absent uptake). The SPECT results were considered abnormal if more than two segments had a stress score > or = 2. Hemodynamic, electrocardiographic and clinical responses were compared with those in a reference group of 100 consecutive age-matched patients undergoing adenosine SPECT who did not have aortic stenosis. RESULTS: Hemodynamic responses during adenosine stress testing between the study and control patients demonstrated no significant difference in the net change in systolic blood pressure (18% of baseline vs. 14%, patients with aortic stenosis vs. control subjects), heart rate (21% vs. 19%), rate-pressure product (0% vs. 2%) or incidence of chest pain (23% vs. 35%) or transient second-(9% vs. 9%) or third-degree atrioventricular block (3% vs. 1%). In the 20 patients who had coronary angiography, sensitivity for detection of coronary artery disease was 92% (12 of 13) and specificity was 71% (5 of 7). CONCLUSIONS: In this preliminary study, adenosine was found to be well tolerated and diagnostically accurate in patients with moderate to severe aortic stenosis. PMID- 7798534 TI - Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins. AB - BACKGROUND: Sulfonamides undergo oxidative metabolism to yield reactive metabolites that haptenate proteins readily. Although it has been shown that sulfonamide metabolites bind covalently to murine microsomes, sulfonamide conjugated serum proteins have not been analyzed in the peripheral blood of treated individuals. OBJECTIVE: We hypothesized that during treatment with sulfamethoxazole, intracellular proteins are haptenated by drug metabolites, and some of these are destined for secretion into the serum. METHODS: Using antibodies specific for sulfamethoxazole and an alkaline phosphatase immunoblotting technique, we attempted to demonstrate the presence of sulfamethoxazole-substituted proteins in the serum of individuals during a course of treatment. RESULTS: Five days into therapy, serum protein haptenation by sulfamethoxazole was demonstrated in two of the three individuals studied. In addition, Western blot analysis revealed that haptenation is not indiscriminate, but highly selective. A single 30 kd protein is the target of haptenation in all instances. A kinetic analysis revealed that substituted proteins can be detected early, within hours of administration. Moreover, haptenated proteins remain detectable in the serum 48 hours after discontinuation of the drug. CONCLUSION: The results presented here constitute the first direct evidence that sulfonamides, on being metabolized, covalently haptenate human serum proteins during a course of therapy. PMID- 7798535 TI - Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma. AB - Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2 staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium. PMID- 7798536 TI - The human nasal response to capsaicin. AB - Airway sensory nerves play a role in reactions to inhaled allergens, irritants, and physical stimuli. Capsaicin, the pungent principle of hot peppers, stimulates a subcategory of sensory nerves. To study the consequences of selective activation of airway sensory nerves in the human nose, we administered capsaicin nasal challenges to eight volunteers (four normal subjects and four subjects with perennial allergic rhinitis). Capsaicin (20 mumol/L), when sprayed into the nose, induced burning, rhinorrhea, and lacrimation. Capsaicin also induced a significant increase in total protein content of nasal lavage fluid after challenge compared with vehicle (increase from before challenge to 1 minute after challenge, 172 +/- 55 vs 46 +/- 29 micrograms/ml, p < 0.001). In contrast to many animal studies, capsaicin did not increase vascular permeability in the airway, because albumin content of nasal lavage fluid was not increased (p = 0.86). On the other hand, lactoferrin, a marker of glandular secretion, was increased (p < 0.005). Repetitive capsaicin challenge every 10 minutes led to tachyphylaxis of symptoms, total protein secretion, and lactoferrin secretion. Compared with vehicle, unilateral capsaicin (6 mmol/L) disk challenge induced significant secretion both ipsilateral (21.3 +/- 4.2 vs 4.9 +/- 2.1 mg, p < 0.01) and contralateral (18.2 +/- 4.4 vs 7.4 +/- 1.9 mg, p < 0.04) to challenge. Thus we have shown that capsaicin challenge to the human nose leads to airway sensory nerve activation. Further, we have demonstrated that capsaicin stimulates a predominantly central neuronal response and that the induced secretory response is of glandular rather than vascular origin. PMID- 7798538 TI - Increased levels of soluble serum interleukin-2 receptor in extrinsic allergic alveolitis correlate with interleukin-2 receptor expression on alveolar macrophages. AB - In a group of 20 patients with extrinsic allergic alveolitis (10 with farmer's lung, 9 with bird-breeder's lung, and 1 with humidifier's lung), we observed increased levels of soluble serum interleukin-2 receptor (ssIL-2R) with an average of 75.2 pmol (control group average, 40.6 pmol). Analysis of bronchoalveolar lavage cells by immunocytochemistry with a CD25 antibody revealed only a slight increase to 4.2% IL-2R+ cells among alveolar lymphocytes but a pronounced rise to 21.2% IL-2R+ cells among alveolar macrophages. Furthermore, cytometry revealed a fourfold higher IL-2R expression on a per cell basis for alveolar macrophages as compared with alveolar lymphocytes. A clear-cut positive correlation (p = 0.006) was found for ssIL-2R and IL-2R+ alveolar macrophages, but only a borderline correlation was found for ssIL-2R and IL-2R+ alveolar lymphocytes (p = 0.04). The finding of a concomitant decrease of IL-2R+ alveolar macrophages and of ssIL-2R on allergen avoidance further supports the notion that alveolar macrophages may be the main source of the increased ssIL-2R in patients with extrinsic allergic alveolitis. PMID- 7798537 TI - Direct evidence for a role of the mast cell in the nasal response to aspirin in aspirin-sensitive asthma. AB - BACKGROUND: A subset of patients with asthma experience adverse nasoocular reactions after ingestion of aspirin or agents that inhibit cyclooxygenase. Recent evidence has implicated the leukotrienes in the nasoocular reaction, but the cellular sources and mechanism of activation are unknown. We used nasal lavage with and without a 5-lipoxygenase inhibitor, zileuton, to define the role of leukotrienes and to profile nasal cellular activation during this reaction. METHODS: A group of eight patients with asthma shown to have adverse reactions to aspirin documented by a 15% or greater decrease in forced expiratory volume in 1 second, accompanied by an elevation in urinary leukotriene E4 after ingestion of aspirin, received aspirin or placebo in a study with a crossover design. Nasal symptoms and nasal tryptase, histamine, leukotriene, and eosinophil cationic protein levels were evaluated. Serum tryptase and urinary histamine levels were also assessed. Subjects were then randomized to receive a week of treatment with zileuton or placebo, according to a double-blind, crossover design followed by aspirin challenge and measurement of the same mediators. RESULTS: Aspirin ingestion produced a marked increase in nasal symptoms from a baseline symptom score of 2.1 +/- 0.7 to a maximum of 8.4 +/- 1.2 (p < 0.0007). Aspirin ingestion produced a mean maximal increase in nasal tryptase of 3.5 +/- 2.6 ng/ml, whereas placebo ingestion produced a mean maximal increase of 0.1 +/- 0.2 ng/ml (p < 0.05, aspirin vs placebo). Mean maximal nasal histamine increased 1.73 +/- 1.16 ng/ml versus 0.08 +/- 0.08 ng/ml from baseline (p < 0.05, aspirin vs placebo). Aspirin produced a mean maximal increase in nasal leukotriene value of 152 pg/ml versus a 16 pg/ml decrease after placebo ingestion (p < 0.05). Zileuton treatment blocked the increase in nasal symptoms after aspirin ingestion (maximum nasal symptom score of 1.6 +/- 0.6 with zileuton vs 5.5 +/- 0.9 with placebo [p < 0.0053]). It also blocked the rise in nasal tryptase (p = 0.011) and nasal leukotriene (p < 0.05) levels after aspirin ingestion. Zileuton treatment had no significant effect on the recovery of nasal histamine. CONCLUSION: The increase in nasal symptoms in aspirin-sensitive patients with asthma after aspirin ingestion is associated with increases in nasal tryptase, histamine, and cysteinyl leukotriene levels. This mediator profile is consistent with mast cell activation during the nasal response to aspirin and suggests that 5-lipoxygenase products are essential for the nasal response to aspirin. PMID- 7798539 TI - Investigating severe and fatal asthma. AB - BACKGROUND: Severe asthma continues to present a major therapeutic problem despite advances in our understanding of the disease. Innovative ideas for investigating the underlying causes and treatment of severe asthma are few, and many patients still become dependent on oral steroids. We describe two separate studies: first, a prospective investigation measuring the responses of persons with severe asthma to an allergen-free environment; second, a retrospective analysis of factors associated with eight fatalities and one near fatality caused by asthma exacerbations. METHODS: In the prospective study 17 persons with severe asthma were admitted to a hospital clinical research unit containing an allergen free room for steroid dose reduction. Peak flow measurements, treatment requirements, and evidence of infection were followed up. In the retrospective study, the cases of nine patients who had been evaluated for asthma and who subsequently died during an asthma attack were reviewed; where possible allergen levels in their house dust and specific IgE antibodies to common indoor allergens were measured. RESULTS: Analysis of the patients in the prospective study revealed two categories of responses to steroid dose reduction: (1) asthmatic persons who either maintained or improved peak flow values on steroid reduction; these patients were predominantly allergic to indoor allergens; (2) asthmatic persons whose condition deteriorated; these patients were unable to tolerate reduction in steroid dose. The second group included persons with sensitization to fungal antigens who had asthmatic exacerbations in association with culture documented fungal colonization. The retrospective study revealed that in five of the eight fatalities caused by asthma, exposure to a relevant allergen had occurred at home before death. CONCLUSION: Some steroid-dependent persons with severe asthma are allergic to inhalant allergens and may benefit from avoiding allergens. In some cases there is no evidence that antigen exposure from diet, inhalants, fungal infections, or sinusitis is relevant to their disease. However, persons with severe asthma include individuals infected with and sensitized to fungal antigens. The results suggest that cases of severe asthma should be investigated to identify treatable causes. PMID- 7798540 TI - House dust mite allergen import into a naturally mite-free environment. PMID- 7798541 TI - Core content outline for clinical and laboratory immunology. AAAI Training Program Directors' Committee. PMID- 7798542 TI - Gene therapy in the treatment of disease. PMID- 7798543 TI - Relationships between total serum IgE, atopy, and smoking: a twenty-year follow up analysis. AB - BACKGROUND: A number of cross-sectional studies have demonstrated that higher levels of IgE are found in subjects who currently smoke cigarettes and/or who are atopic and that IgE levels decline with age. OBJECTIVE: This report examines the interactions among atopic status, smoking, and IgE with longitudinal data and methods. METHODS: Subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease and were 6 years of age and older. Total serum IgE measures and allergen skin test results were obtained during three surveys spanning a period of up to 20 years. RESULTS: The results showed no significant gender differences between nonatopic nonsmoking subjects, who were considered the reference group. Nonatopic current smokers had IgE levels similar to those of the reference subjects initially, but IgE levels did not decline with age at the same rate as in the reference subjects, causing significant differences at older ages. There was a significant relationship between number of cigarettes smoked and IgE level. CONCLUSIONS: Atopy and smoking are both associated with elevated total serum IgE levels. Although the exact mechanism for elevated IgE levels in smokers is not known, the significant dose relationship is suggestive of a causal association. PMID- 7798544 TI - The role of eosinophils and eosinophil cationic protein in monitoring oral challenge tests in children with food-sensitive atopic dermatitis. AB - To investigate the role of peripheral blood eosinophils and eosinophil cationic protein as parameters in monitoring oral food challenges, we monitored 25 infants and children with atopic dermatitis for up to 48 hours after 47 placebo controlled oral food challenges with cow's milk, hen's egg, cow's milk and hen's egg, or placebo for up to 48 hours. Six healthy young nonatopic adult volunteers served as control subjects. Compared with baseline values, peripheral blood eosinophils decreased significantly immediately after clinical reaction in positive challenges (p < 0.0004), independent of the kind of reaction. Eosinophil cationic protein increased significantly 8 hours after provocation, with a maximum at 24 hours (p < 0.03). This increase was predominantly related to eczematous reactions (p < 0.005). Blood sampling immediately after clinical reaction (for eosinophils) and at 24 hours (for eosinophil cationic protein) seems to be useful in monitoring oral food challenges in children with atopic dermatitis. PMID- 7798545 TI - A dose-ranging study of the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis with an acute model. AB - BACKGROUND: Oral azelastine, a nonsteroidal antiinflammatory respiratory investigational drug has demonstrated activity in the treatment of allergic rhinitis and asthma with a good safety profile. METHODS: Azelastine nasal spray was compared with sustained-release oral chlorpheniramine maleate and placebo for efficacy and safety in the treatment of seasonal allergic rhinitis in a double dummy, two-center, 2-day, double-blind, randomized, dose-ranging, parallel groups, onset and duration of action study. Two hundred sixty-four subjects reported to an outdoor park on Saturday morning during the height of the fall pollen season and remained there for 8 hours that day and the next to ensure maximal exposure to seasonal aeroallergens. Symptom diary cards were collected hourly Saturday from 8:00 AM to 10:00 AM (baseline period). Subjects who had sufficient symptoms were randomized into five groups and received medication at 10:00 AM and 10:00 PM on Saturday and at 10:00 AM on Sunday: azelastine 0.1% (1 spray [0.12 mg] per nostril every 12 hours, 2 sprays per nostril every every 12 hours, or 2 sprays per nostril once daily), Chlor-Trimeton Repetabs (12 mg twice daily), or placebo (twice daily). Diary cards were completed hourly (11:00 AM to 4:00 PM) and at 6:00, 8:00, and 10:00 PM on Saturday and again hourly on Sunday (from 8:00 AM to 4:00 PM) to evaluate rhinitis symptoms and adverse events. RESULTS: Two hundred fifty-nine subjects completed the study. The groups that received 2 sprays of azelastine per nostril once and twice daily and the chlorpheniramine group had statistically significantly more improvement in total rhinitis symptoms than the placebo group without serious adverse events. CONCLUSIONS: This study supports a once to twice daily dosing regimen for 2 sprays of 0.1% azelastine in the acute treatment of allergic rhinitis with onset of action within 2 to 3 hours. PMID- 7798546 TI - Total serum IgE and eosinophil count in children with and without a history of asthma, wheezing, or atopy in an urban community in Indonesia. The Respiratory Disease Working Group. AB - AIM: The objectives of the study were to assess total serum IgE and eosinophil count in a random sample of 20% of the children between 12 and 54 months old in a suburban community of Bandung, Indonesia, and to investigate a possible relationship between these values and atopy, asthma or wheezing and parasite infestation. METHODS: Two hundred sixty-nine children were examined at the Integrated Primary Health Care Unit, and the parents or guardians were interviewed with the use of a standardized questionnaire. RESULTS: The overall median value of IgE was 436 IU/ml (range, 18 to 9707 IU/ml); almost 94% of the children showed an IgE value of more than 100 IU/ml, and 29% showed a value of more than 1000 IU/ml. The median value for eosinophils was 580/mm3 (range, 70 to 5090/mm3); only 31% of the children had less than 400 eosinophils/mm3. IgE levels and eosinophilia were not related to age but showed a significant, although not high, correlation with each other (p < 0.05). In about 36% of the children parasites were demonstrated in a single stool sample; in those subjects eosinophilia and IgE values tended to be greater, but the difference was not significant. About 7% of the children had asthma, and in those subjects the eosinophil counts and IgE levels were much more increased (p < 0.001 and p approximately 0.01, respectively). No difference was found in IgE or eosinophil count in relation to other forms of atopy in the child (milk-induced dermatitis, urticaria, eczema, rhinitis) or in relation to a history of asthma or atopy in other family members. Yet, the occurrence of asthma in the child was significantly related to a history of asthma in other family members. CONCLUSIONS: IgE values and eosinophilia are markedly increased in these children under 5 years of age in Bandung, Indonesia, and the highest values are found in the 7% with asthma. PMID- 7798547 TI - Characterization of Der p V allergen, cDNA analysis, and IgE-mediated reactivity to the recombinant protein. AB - A lambda gt11 library for cDNA from Dermatophagoides pteronyssinus was screened by plaque immunoassay, and a number of related clones that produced IgE-binding proteins were isolated. Their sequences were homologous to that of a cDNA described previously, which contained a reading frame encoding a 17 kd polypeptide and which as determined by serologic analysis corresponded to a protein with relative molecular mass of 14 kd in mite extracts. The cDNA from the lambda gt11 clones was truncated so it was used to obtain longer clones from a lambda gt10 library. Analysis of the sequence of these clones showed that the allergen now designated Der p V is produced from a 132-residue polypeptide, which has a putative 19-residue leader peptide and a 113-residue mature protein. This would have a molecular weight of 14 kd, corresponding to that found in mite extracts. IgE binding studies with the lambda gt11 clone and a fusion of the mature sequence in a pGEX construct showed that it reacted with 50% of allergic sera. Further studies with skin tests indicated that it caused reactions in about 60% of patients with asthma and 29% of those with allergic rhinitis alone. PMID- 7798549 TI - The Role of Basophils and Eosinophils in Human Disease. Proceedings of a meeting. Cabo San Lucas, Mexico, March 10-13, 1994. PMID- 7798548 TI - Modulation by interleukin-4 of cytokine release from mononuclear phagocytes in asthma. AB - BACKGROUND: Interleukin (IL)-4 is involved in IgE upregulation and downregulates cytokine release by mononuclear phagocytes. Mononuclear cells release greater amounts of IL-1, tumor necrosis factor-alpha, and IL-6 in patients with asthma than in control subjects, but the effect of IL-4 on cells from patients with asthma is unknown. The effects of IL-4 on the release of IL-1, tumor necrosis factor-alpha, and IL-6 by monocytes and alveolar macrophages were compared in 19 patients with asthma and 18 control subjects. METHODS: The release of IL-1, tumor necrosis factor-alpha, and IL-6 from unstimulated and lipopolysaccharide stimulated monocytes and alveolar macrophages was measured by ELISA. The effect of 30 U of IL-4 on the release of these cytokines was studied. RESULTS: Lipopolysaccharide-stimulated monocytes released significantly fewer cytokines in patients with asthma than in control subjects. IL-4 significantly inhibited cytokine release by monocytes of both groups. Unstimulated alveolar macrophages from patients with asthma released more cytokines than those of control subjects. Lipopolysaccharide induced a significantly greater increase in cytokine release in alveolar macrophages of control subjects in comparison with asthmatic subjects. IL-4 abolished the release of cytokines in alveolar macrophages from control subjects and had a minimal inhibitory effect on alveolar macrophages from patients with asthma. CONCLUSIONS: Alveolar macrophages from patients with asthma are hyperreactive but less prone to lipopolysaccharide stimulation and IL-4 downregulation than those from normal subjects. PMID- 7798550 TI - Similarities in the ultrastructural morphology and developmental and secretory mechanisms of human basophils and eosinophils. PMID- 7798551 TI - Initial events in Fc epsilon RI signal transduction. AB - Our current model of the events that occur in the first few seconds after Fc epsilon RI cross-linking focuses primarily on the role of tyrosine phosphorylation and its ability to direct specific protein-protein interactions through SH2 domains. Contact of a mast cell bearing appropriately liganded Fc epsilon RI with multivalent antigen results in the approximation of receptors initially into chains. The proximity of receptors in these chains allows the phosphorylation of their ARAMs by the lyn tyrosine kinase. ARAM phosphorylation results in binding of syk specifically to cross-linked receptors and its probable subsequent phosphorylation and activation by lyn. Activated syk then phosphorylates and activates PLC gamma 1 and PLC gamma 2, resulting in their activation and translocation to the membrane. The presence of active PLC gamma 1 and PLC gamma 2 on the cell membrane results in hydrolysis of membrane phosphatidyl inositol and the production of 1,4,5 inositol triphosphate. Inositol 1,4,5 triphosphate diffuses to the sarcoplasmic reticulum and causes the release of sequestered calcium. This model represents a snapshot of the current body of knowledge about Fc epsilon RI-mediated signal transduction. Given the rapid pace of research in this field, it will likely be incorrect or incomplete in at least some respects by the time of publication. Ideally, the information presented here should provide a framework on which to build for those interested in learning more about Fc epsilon RI in particular and multisubunit antigen receptors in general. PMID- 7798552 TI - Signal transduction: mechanisms in basophils. PMID- 7798553 TI - Lipid bodies: intracellular sites for eicosanoid formation. AB - Lipid bodies, therefore, represent specialized intracellular domains that form rapidly in response to agents that activate protein kinase C. These structures contain eicosanoid-precursor arachidonate esterified in specific phospholipids. Arachidonate-releasing phospholipases probably act at lipid bodies, and an eicosanoid-forming enzyme, PGH synthase (cyclooxygenase), definitely localizes to lipid bodies. In addition, the heightened presence of lipid bodies in cells likely to be producing eicosanoids as part of inflammatory reactions indicates that lipid bodies are dynamic, specialized intracellular domains with roles pertinent to the metabolic transformation of arachidonate into paracrine mediators of inflammation. With their prominence in cells in association with inflammation, lipid bodies constitute specialized sites at which eicosanoid formation could occur for the heightened generation of eosinophil eicosanoid mediators of inflammation. This compartmentalization of eicosanoid formation at lipid bodies would provide a nonmembrane pool of arachidonate whose metabolic utilization could occur without perturbation of membranes if membranes were the sole stores of substrate fatty acid used for quantities of eicosanoids synthesized as paracrine mediators of inflammation. Moreover, lipid bodies would serve as sites at which the coordinated and regulated enzymatic events involved in arachidonate mobilization and oxidative metabolism could occur. PMID- 7798554 TI - Function and expression of adhesion molecules on human basophils. PMID- 7798555 TI - Eosinophil adhesion in allergic inflammation. AB - Eosinophil adhesion has been studied in some detail in recent years, and a number of interesting observations have emerged. As with other aspects of eosinophil biology, there appears to be a greater similarity with basophils than with neutrophils in their pattern of adhesion interactions. A number of important differences with respect to neutrophils have emerged, which could be exploited for the treatment of eosinophil-mediated disease, including the observations that eosinophil adhesion can be modulated by selective cytokines such as IL-5 and that eosinophils, unlike neutrophils, express VLA-4 and alpha 4/beta 7. There is also tantalizing evidence emerging that eosinophils interact differentially with the selectins, with differing degrees of affinity of binding and possibly different counterreceptors. The extent to which these observations will be useful in treating allergic disease remains to be seen. PMID- 7798556 TI - Distinguishing features of basophil and neutrophil activation by major basic protein. PMID- 7798557 TI - The phenotype of human eosinophils, basophils, and mast cells. PMID- 7798558 TI - Cytokine generation by eosinophils. PMID- 7798559 TI - Cytokine generation by human basophils. PMID- 7798560 TI - Acquisition of lymphokine-producing phenotype by CD4+ T cells. PMID- 7798561 TI - The effects of glucocorticoids on human eosinophils. AB - It is readily apparent that eosinophils are important targets of steroid effects. Disruption of the cytokine network by glucocorticoids can indirectly diminish eosinophil generation, survival, and function. In addition, glucocorticoids appear to have direct effects on the survival, and perhaps on the function, of these cells. Rapid advances in our knowledge of the biochemistry of signal transduction, as well as the interaction between cell surface receptors and RNA transcription machinery, will allow detailed analysis of the mechanisms by which the function and life cycle of eosinophils are influenced by glucocorticoids. PMID- 7798562 TI - The high-affinity IgE receptor on eosinophils: from allergy to parasites or from parasites to allergy? PMID- 7798563 TI - Mechanisms of allergic pulmonary eosinophilia in the mouse. PMID- 7798565 TI - Development of markers for human basophils and mast cells. PMID- 7798564 TI - The eosinophil-mediated antitumor activity of interleukin-4. PMID- 7798566 TI - The skin as a model to study the pathogenesis of IgE-mediated acute and late phase responses. PMID- 7798567 TI - Cytokine control of eosinophils in pulmonary diseases. PMID- 7798568 TI - Tyrosine phosphorylation and inositol phosphate production: are early events in human eosinophil activation stimulated by immobilized secretory IgA and IgG? AB - Eosinophils are implicated as major inflammatory cells in parasite infection and allergic reactions. Among various mediators, eosinophil granule cationic proteins play an important role in the pathophysiology of diseases. However, little is known about the actual physiologic stimuli for eosinophil degranulation and the signaling events for triggering eosinophil degranulation. A series of in vivo and in vitro studies suggest that the interaction between antibody coated parasites and Fc receptors on eosinophils is one of the most effective triggers for eosinophil degranulation. Similarly, eosinophil degranulation can be induced in vitro by Sepharose beads coated with human sIgA or IgG. Eosinophil degranulation induced by these stimuli is mediated by PTX-sensitive membrane-bound heterotrimeric G protein(s), and is accompanied by the rapid turnover of inositol phosphates. The production of inositol phosphates is inhibited by PTX. Eosinophil activation by sIgA and IgG also involves tyrosine phosphorylation of several proteins and is inhibited by tyrosine kinase inhibitors. Thus phospholipase C coupled G protein(s) and tyrosine kinases are key molecules in early signal transduction of eosinophil activation induced by sIgA and IgG. Although further studies are needed to identify which tyrosine kinase(s) is specifically involved in the eosinophil degranulation mechanism, these molecules could be a target for therapies of human diseases where eosinophils are involved. PMID- 7798569 TI - Biochemical properties, activities, and presence in biologic fluids of eosinophil granule major basic protein. AB - The existence of a proform of MBP is predicted from the sequence of MBP cDNA clones. ProMBP has been purified from the supernatants of CHO cells transfected with cDNA encoding prepro MBP. Purification involved heparin-Sepharose affinity purification followed by two sequential size fractionation steps over Sephadex G 100 and yielded proMBP with a molecular mass of 33 kd. Recombinant proMBP from the heparin-Sepharose column was subjected to isoelectric focusing followed by SDS-PAGE and Western blot analysis. The results indicated that most of the 33 kd form of proMBP focused predominantly between pI 4.2 and 5.1, with a major peak at a pI of approximately 4.9. Analyses of the carbohydrates associated with the purified 33 kd form of recombinant proMBP indicated the addition of 4856 to 5150 Da by carbohydrates characteristic of the complex type. Consistent with the hypothesis that the function of the propiece is to neutralize MBP toxicity during granule processing, proMBP lacked MBP cytostimulatory properties and actually blocked the effect of MBP in two different systems, basophil histamine release and neutrophil activation. In addition, as a measure of toxicity, proMBP did not inhibit protein synthesis, whereas MBP markedly reduced protein synthesis. The mechanisms by which MBP exerts its actions both as a cytostimulant and as a toxin are not known; however, it is known that cationic MBP readily reacts with acidic lipids. Using artificial liposomes as targets, MBP caused a disordering of the lipid bilayer membrane, resulting in fusion and lysis. Therefore, MBP may act both as a cytostimulant and as a toxin because of its marked cationicity and its ability to disorder lipid membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798570 TI - Cytokines and allergy. PMID- 7798571 TI - Eosinophils in atopic dermatitis. PMID- 7798572 TI - Response of six patients with idiopathic hypereosinophilic syndrome to interferon alfa. PMID- 7798573 TI - Using a bony landmark to measure waist circumference. PMID- 7798574 TI - Visionary leaders are key to success in foodservice. PMID- 7798575 TI - New 'healthy meals' legislation promises improved child nutrition programs but GOP 'contract' may dismantle progress. PMID- 7798576 TI - Practical and legal considerations of private nutrition practice. PMID- 7798577 TI - Resting energy expenditures measured by indirect calorimetry are higher in preadolescent children with cystic fibrosis than expenditures calculated from prediction equations. AB - OBJECTIVE: This study compared measured resting energy expenditures to resting energy expenditures calculated using Harris-Benedict equations (HBEs) and the Cystic Fibrosis Consensus Committee equations (CFCCEs). DESIGN: We studied 31 preadolescent boys and girls with cystic fibrosis who ranged in age from 3.25 to 12.75 years old. The patients were afebrile and not in pulmonary distress. Measured resting energy expenditures were determined using a portable metabolic measurement cart with fully automated calibration and data management. The measured resting energy expenditures obtained were compared with values obtained using HBEs and CFCCEs. RESULTS: For each patient, the measured resting energy expenditure value was above the predicted resting energy expenditure values derived from HBEs (P < or = .0001) and CFCCEs (P < or = .01). APPLICATIONS: The HBEs and the CFCCEs underestimated the energy expenditures of the study population by 13% and 8%, respectively. These findings support the usefulness of the measurement of energy expenditures in determining the energy needs of preadolescent patients with cystic fibrosis. In clinical practice, the resting energy expenditures would be multiplied by activity coefficients to determine the total daily energy expenditures of this population. PMID- 7798578 TI - Moderators and determinants of satisfaction with diet counseling for patients consuming a therapeutic diet. AB - OBJECTIVE: To identify moderators and key determinants of patient satisfaction with diet counseling. DESIGN: Survey questionnaire. SETTING: A French-Canadian acute-care urban hospital. SUBJECTS: Population of eligible patients hospitalized for a minimum stay of 5 days. Patients excluded from the study were those with notable physical, cognitive, or emotional limitations; those receiving enteral and parenteral nutrition; and those from long-term-care units. Analyses were performed on 49 patients who consumed a therapeutic diet and who received diet counseling during their current hospital stay. MAIN OUTCOME MEASURES: Overall satisfaction with diet counseling, compliance intentions, and satisfaction with four components of diet counseling. Measures were taken on seven-point graphic scales and five-point semantic scales. STATISTICAL ANALYSIS: Reliability estimates with Cronbach's alpha correlation coefficient, stepwise multiple regression analyses, t tests, and one-way analyses of variance. RESULTS: Facilitation skills and knowledge components of diet counseling were the key determinants of patient satisfaction. Among the moderators of patient satisfaction with diet counseling, women and patients with a good appetite were more satisfied with the knowledge components and had stronger compliance intentions. Patients who spent more than 50% of the time at rest were less satisfied than more active patients. APPLICATIONS: Enhancing patient satisfaction implies having a good understanding of a patient's social and cultural context, developing problem-solving skills, and demonstrating greater flexibility and creativity about the means of providing diet counseling. PMID- 7798580 TI - Protein quality of enteral nutrition products is consistent with label claims during shelf life and beyond expiration date. AB - OBJECTIVE: Eternal formulas were monitored during their shelf life and beyond expiration date to examine protein quality. DESIGN: Protein quality was determined by protein efficiency ratio (PER) bioassays and amino acid analyses. SETTING: A certified laboratory performed the PER tests according to procedures established by the Association of Official Analytical Chemists and recognized by the US Food and Drug Administration (FDA). The amino acid analyses were performed in our laboratory using validated methods. SAMPLES: Commercially available formulas (Ensure, Osmolite HN, TwoCal HN) that contained protein blends of caseinates or caseinates with soybean protein isolate were studied. MAIN OUTCOME MEASURES: Achievement of protein-quality values greater than or equal to 70% of the fresh reference casein value as determined by the PER method would be consistent with adequate protein quality as described by the FDA. Levels of indispensable amino acids that meet or exceed the standards established by the National Research Council of the National Academy of Sciences are considered high quality proteins. Levels of amino acids throughout shelf life were compared with published label claims. RESULTS: Amino acid analyses, which included measurement of tryptophan and total sulfur amino acids, revealed that both fresh and outdated products met or exceeded standards for proteins of high biologic value and were consistent with label claims. The PER values ranged from 90% to 96% of the control diet for fresh product and 82% to 87% for products evaluated after expiration. CONCLUSION: The enteral products studied provide high-quality protein throughout the shelf life of the product. PMID- 7798579 TI - Corn bran supplementation of a low-fat controlled diet lowers serum lipids in men with hypercholesterolemia. AB - OBJECTIVE: The purpose of this study was to determine the lipid-lowering effects of dietary corn bran fed in moderate supplemental doses to men with hypercholesterolemia consuming a low-fat diet. DESIGN: The 98-day study was divided into one 2-week preperiod and two 6-week experimental periods in a cross over design. SETTING: The study was conducted in the metabolic diet kitchen of the Department of Home Economics and the Nutrition Research Laboratory of the Department of Agriculture at Illinois State University, Normal. SUBJECTS: Twenty nine sedentary men with hypercholesterolemia, aged 38 to 70 years, participated in the project. All of them completed the study. INTERVENTIONS: After a 2-week adjustment period in which subjects consumed a low-fat controlled diet, subjects were assigned to one of two experimental treatments: low-fat controlled diet plus 20 g corn bran supplement or low-fat controlled diet plus 20 g wheat bran supplement. MAIN OUTCOME MEASURES: Lipid measurements included total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and triglyceride concentrations. STATISTICAL ANALYSES PERFORMED: Differences in lipid parameters were analyzed using two-way analysis of variance with repeated measures (P < .05). A paired t test was used to assess differences between treatment periods for each subject. RESULTS: The low-fat controlled diet significantly lowered all serum parameters analyzed except HDL-C. Corn fiber supplementation resulted in an additional lowering of serum total cholesterol, triglyceride, and VLDL-C concentrations. Serum LDL-C and HDL-C concentrations were not significantly altered by corn fiber or wheat fiber supplementation. APPLICATIONS: This study suggests that supplementing a low-fat diet with corn bran is affective in reducing serum lipid concentrations for men with hypercholesterolemia. PMID- 7798581 TI - Advances in molecular biology: implications for the future of clinical nutrition practice. AB - Advances in molecular biology during the past decade have substantially contributed to our understanding of how genes influence physiologic processes and, ultimately, our health. Genes associated with many nutrition-related chronic diseases are being identified and characterized. Nutrients may directly or indirectly influence the transcription and/or translation of specific gene products. Identifying genetic markers for specific diseases and exploring gene therapy will provide new opportunities and challenges for clinical nutrition practice in the 21st century. Nutrition practitioners must be cognizant of developments in molecular biology to meet the challenges of providing nutrition care in the future. PMID- 7798582 TI - Waist-to-hip ratio in a biracial population: measurement, implications, and cautions for using guidelines to define high risk for cardiovascular disease. AB - Cutoff points for high waist-to-hip ratio (WHR) that may define high risk for cardiovascular disease have been suggested for men (0.95) and women (0.80). The WHRs of groups defined by age, race, and sex among 3,118 South Carolina adults were compared with these cutoff points. Measurement methodology, mean WHRs, and prevalence of elevated WHR in this biracial study population were compared with data from other populations. A review of anthropometric measurement methods used in recent epidemiologic studies indicates that a standard method for measuring waist and hip girth is required before comparisons of mean levels can be valid. The paucity of evidence that a high WHR is associated with cardiovascular disease mortality in black populations, and the high number of women who have an elevated WHR in this and other epidemiologic studies, support the following conclusion: Current WHR cutoff points, which are based on evidence from primarily white populations, may not be appropriate for women, older age groups, and some racial or ethnic groups in the United States. PMID- 7798583 TI - Continuous quality improvement in inpatient clinical nutrition services. AB - Defining quality patient care is a complex and often confusing issue. This article describes one hospital's experience in applying quality improvement theories to inpatient clinical nutrition practice. The key to measuring quality was the use of standardized practice guidelines. In this article, terms such as continuous quality improvement are clarified and fundamental assumptions such as "quality is defined as conformance to requirements" are discussed. We review a working model for the 10-step plan of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and its application in practice, including the indicators and measurement tools used. Actual results from ongoing quality improvement efforts are addressed and compared to the JCAHO nine components of quality patient care. Because of preexisting nutrition practice guidelines at the Yale-New Haven Hospital, improvements in the delivery of patient nutrition care could be demonstrated; these included enhanced efficiencies in screening and intervention. Continuous quality improvement initiatives do work, and practitioners can use the practice experience presented here as a conceptual framework to justify or validate the quality of patient nutrition care in their own institutions. PMID- 7798584 TI - Criteria for acceptance to preprofessional dietetics programs vs desired qualities of professionals: an analysis. AB - The objectives of this analysis were to examine the literature and compare and contrast (a) qualities preferred in preprofessional dietetics students by directors of internships and approved preprofessional practice programs (AP4s), (b) characteristics needed to succeed in a scientific field, (c) traits emphasized by dietetics training programs compared with those most valued by employers, (d) skills needed by high-level managerial dietitians and those in business and communications, and (e) qualities dietitians have aspired to develop for increased competitiveness in the marketplace. Even though the revised Standards of Education have been in place since 1988, recent evaluation of criteria for internship and AP4 admission has shown traditional emphasis on academic performance and the importance of work experience. Success in scientific pursuits has been linked with more than innate intelligence; a drive for success and enthusiasm for learning are also involved. Internships foster mostly technical learning, so development of skills in human and conceptual areas are somewhat lacking. These skills, which have been identified as valuable to employers, need greater development or more consistent identification in the selection and training process. Perhaps serious consideration should be given to applicants for preprofessional programs who have shown leadership qualities through extracurricular activities or who have given themselves the opportunity to develop and improve these skills. Such students might hasten the metamorphosis of dietetics practitioners toward improved levels of compensation and professional fulfillment. PMID- 7798585 TI - Tea and coffee brews are not dietary sources of vitamin K-1 (phylloquinone). PMID- 7798586 TI - Consumer preferences among nutrition labeling formats in a restaurant. PMID- 7798587 TI - Value of theoretically based cooking classes for increasing use of commodity foods. PMID- 7798588 TI - Position of The American Dietetic Association: cost-effectiveness of medical nutrition therapy. PMID- 7798589 TI - Summary: weighing the options--criteria for evaluating weight-management programs. Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. PMID- 7798590 TI - The induction of cytokine gene expression in murine peritoneal macrophages by Pseudostellaria heterophylla. AB - We have previously shown that a mitogenic fraction (PH-I) separated from Pseudostellaria heterophylla (P. heterophylla) could act as a priming agent for the release of tumor necrosis factor-alpha (TNF-alpha) in mice. In the present study, PH-I was further purified by gel filtration chromatography and the resulting three fractions (PH-I A, PH-I B and PH-I C) were assessed for the induction of TNF-alpha, interleukin-1-alpha (IL-1-alpha) and IL-1-beta gene expression in mice by enzyme-linked immunosorbent assay and polymerase chain reaction. It was found that fraction PH-I C from P. heterophylla was the most potent priming fraction among the three fractions for the induction of TNF-alpha in serum and the TNF-alpha mRNA in murine macrophages. Moreover, all three fractions were found to increase the expression of IL-1-alpha mRNA while PH-I C showed the most potent activating effect on the expression of IL-1-beta mRNA. PMID- 7798591 TI - Induction of apoptosis in mouse thymocytes by cyclosporin A: in vivo study. AB - We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis. PMID- 7798592 TI - Inhibition of phytohaemagglutinin-induced lymphocyte proliferation by immunosuppressive drugs: use of whole blood culture. AB - A whole blood lymphocyte proliferation assay was compared to a standard method requiring the isolation of lymphocytes from blood. Both methods were used to measure inhibition of proliferative responses of phytohaemagglutinin (PHA1) stimulated human peripheral blood lymphocytes by tacrolimus (FK 506(1)), cyclosporine A (CsA1), rapamycin (RA1), dexamethasone (DEX1), prednisolone (PR1), and methylprednisolone (MP1). Three of the drugs studied (FK 506, CsA, and DEX) yielded similar IC50 values with both methods. The whole blood proliferation assay produced modestly lower IC50 values for RA, PR and MP. The whole blood lymphocyte proliferation method is simple and can be used when only limited volumes of blood can be obtained or isolation of cells gives unsatisfactory yields. PMID- 7798593 TI - Prothymosin alpha and factors from calf thymic cells decrease expression of Thy 1.2 antigen among small thymocytes from C57BL/6 mice. AB - In this work we studied the effect of Prothymosin alpha (ProT alpha) and other thymic factors on the expression of Thy 1.2 antigen (a T-cell marker) and the activities of adenosine deaminase (ADA, E.C. 3.5.4.4), N-acetyl-beta-D glucosaminidase (NABG, E.C. 3.2.1.30), beta-glucuronidase (BG, E.C. 3.1.1.1) and serine-esterase (SE, E.C. 3.4.21)., the levels of which change during the T-cell differentiation process among small thymocytes obtained from C57BL/6 mice. Incubation of small thymocytes in the presence of ProT alpha, Thymus Extracts (TE) or supernatants prepared from thymic stromal cells (TSCS) or thymocytes (TS) reduced the proportion of cells killed by anti-Thy 1.2 monoclonal antibodies but did not affect the enzymatic activities studied. This is the first evidence that ProT alpha affects Thy 1.2 expression in vitro. PMID- 7798594 TI - Modulation of amphotericin B activity by association with mannose ester. AB - The biological and molecular properties of a new formulation of Amphotericin B complexed with the surfactant palmitoyl mannose were studied in in vitro as well as in in vivo situations. The properties analyzed include toxicity towards two types of mammalian cells and four fungi strains, effect on macrophage activity, inflammatory properties, acute toxicity in mice and spectral behavior in presence of foetal calf serum or 6% propanol. The results demonstrate that, in presence of palmitoyl mannose, the cytotoxicity of AmB is decreased towards both, fungal and mammalian cells while its fungistatic potential is increased, its inflammatory properties are conserved and its acute toxicity is significantly diminished. These effects can be potentially explained by the formation of a complex between AmB and the sugar ester that impedes the interaction of the drug with either serum components or cell membrane constituents. The overall properties of AmB in the complex would be expected to favor an increase in the immunoadjuvant properties of the drug, a more localized inflammation during fungal infection and consequently a better therapeutic efficiency. PMID- 7798596 TI - Immunomodulating effect of met-enkephalin on different stages of lymphocyte proliferation induced with concanavalin A in vitro. AB - Met-enkephalin (ME) in the range of concentrations 10(-15) M to 10(-9) M has exhibited an immunomodulating effect on concanavalin A (Con A) induced proliferation of mice lymphocytes from lymph nodes in vitro. The effect of ME was shown to vary with the stage of lymphocyte activation and to depend on the mitogen dose. In the case that ME and Con A were injected simultaneously, at the zero time of proliferation, maximum inhibition was observed on the first and fourth days. In an other set of experiments when ME was added at intervals of 4 hours before measuring the proliferation response value, both inhibition (after 24 hours of proliferation) and stimulation (after 28 and 96 hours) were observed. Opioid ligands of various classes were found to act in the same manner as ME. Naloxone was shown to block the immunomodulating effect of opioids. PMID- 7798595 TI - In vivo effect of omeprazole on HLA-DR expression and the monocyte-macrophage function in patients with duodenal ulcer disease. AB - It is not known if omeprazole possesses any action on immune system. Therefore, we examined the effect of omeprazole on parameters of cellular immunity [T-cell subsets-CD3+, CD4+, CD(8+)- and HLA-DR expression on peripheral blood lymphocytes (PBLs)] and on function of peripheral blood monocyte-macrophages (PBMMs) [random migration (RM), directed migration (DM), phagocytosis index (P-I) and HLA-DR expression] in 13 duodenal ulcer patients before and during 3-mo omeprazole treatment. The number of T-cell subsets varied at pretreatment values (p > 0.05), whereas the percentage of HLA-DR positive PBLs increased significantly after 3-mo therapy (p < 0.001). On the other hand, all studied parameters concerning PBMMs (RM, DM, P-I and HLA-DR expression) increased significantly after 3-mo therapy (p < 0.001, p < 0.001, p < 0.003, p < 0.001, respectively vs. baseline values). In conclusion, omeprazole exerts an immunopotentiating effect on functions of PBMMs and may also influence T-cell function. These effects can be considered as an advantage of omeprazole in long-term treated patients with peptic ulcer disease. PMID- 7798597 TI - Gay and lesbian studies in art history. PMID- 7798598 TI - Ambiguity and the image of the king. AB - The following essay explores problems posed by a recently-published fresco (dated to the first century AD) that depicts Alexander the Great standing opposite an unknown female figure. The fresco is unusual in its use of conventional or codified figure types, in particular a widely-found statue type known as the "Alexander with the Lance," and for its placement of Alexander in anecdotal relation with a woman. While discussions of the picture thus far have tried to identify the scene depicted (by reference to histories of Alexander's life), the following analysis takes the difficulty of doing so itself as a motivated aspect of the image. I argue that the fresco's mode of representation is to bring together figure types whose conventional fields of meaning are in conflict with one another, and then to highlight this conflict in order to comment upon the fields (or figure types) themselves. In this case, the fresco's ambiguity in signification (the undecidability of its reference) enables a highly strategic critique of the "Alexander with the Lance" because the latter, as a prototypical "image of the king," depends upon the necessary and transparent extension of its signs. By virtue of the anecdotal relation between "Alexander" and the depicted female figure (an Aphrodite type) the fresco's critique reveals the close association between the claims for representation made by the image of the king and the patriarchal structures of power they seek to instantiate. The fresco thus offers remarkably direct data for understanding the intersection of representation and gender in the early Roman empire. I suggest in conclusion that because the image seems also to posit a specifically gendered (male) gaze, its critique is extended to the spectator and thereby provides data for understanding the intersection of the practice of representation (here, viewing) and gender. PMID- 7798599 TI - Lesbian sightings: scoping for dykes in Boucher and Cosmo. AB - In Cosmopolitan magazine and in the work of the eighteenth-century French painter Francois Boucher, lesbians are visible, but nobody seems to notice. The operation of covert invisibility in such disparate cultural products suggests that the closet metaphor and the common idea that queer visibility generates queer empowerment must be retained but rethought. It also suggests that queer scholars and activists can benefit from occasionally working as historical-specificity outlaws, which here brings into focus the distinct ideological affects of each product, as well as some shared ones that demand our attention, including the disarticulation of female political activism, and the promotion rather than subversion of hetero-hegemony. PMID- 7798601 TI - The abject gaze and the homosexual body: Flandrin's Figure d'Etude. AB - This article charts the history of the reception, reproduction and appropriation of a single image that has recently become a kind of "gay icon"--the Figure d'Etude in the Louvre, painted by Hippolyte Flandrin in 1835. Initially no more than a neo-classical academic exercise, the formal emptiness of this picture meant that it could be re-invested and reinscribed with new meanings and new titles at every turn. Emblematic of the anxious visibility/invisibility of the newly discovered homosexual body during a period when the gaze still had to be kept a dark secret, Flandrin's image only "came out" in its later photographic reworkings by Frederick Holland Day and Baron von Gloeden. After being reproduced for a specifically homosexual audience early this century, the popular Romantic pose of the young man curled-up in profile became a standard one, reappearing recently in the photographs of Robert Mapplethorpe. The inactive, abject and inward-turned isolation of the figure with its narcissistic self-absorption makes it, in my view, a profoundly negative stereotype of the gay gaze and the homosexual body. Flandrin's figure nonetheless appears today on gay merchandise world-wide as a sign of our separate and secluded subject positions and our community's unwillingness to radically alter older imposed and inherited classical stereotypes. PMID- 7798600 TI - Winckelmann divided: mourning the death of art history. AB - The discipline of art history is often said to have been invented in the writing of J.J. Winckelmann (1717-1768). In his Reflections on the Imitation of Greek Works in Painting and Sculpture (1754) and History of Ancient Art (1764), Winckelmann dealt with the homoerotic meanings of Greco-Roman arts in complex ways. To do so, he imagined a split between his subjective position as an observer with specific erotic and political interests and his objective position as an historian. His importance for art historians today derives from his own recognition and further elaboration of his "division," an awareness manifested in his principal metaphor for the status of the art historian as a "maiden" mourning her "lover," the "lost object" of her desire, namely, ancient representations of beautiful young men. This metaphor and related features of Winckelmann's texts situated the homoeroticism of art and of the art historian in mutual relations that enable the art historian to reconcile, if not to resolve, his fundamental "division." Winckelmann's image of art history presents a more adequate sense of the enterprise than the misleading polarization of "objective" history and "subjective" interpretation frequently encountered today. PMID- 7798602 TI - Making history: the Bloomsbury group's construction of aesthetic and sexual identity. AB - This essay examines the way England's well-known Bloomsbury group in the first decades of this century negotiated the legacy of prominent figures of the generation before in order to create its own identity. Looking at the group's ideas about both aesthetics and sexuality, the author shows how the group privileged Leo Tolstoy over J. A. M. Whistler, and Oscar Wilde over Walter Pater. The introduction and conclusion seek to set this study in the context of current issues in gay and lesbian studies. PMID- 7798603 TI - Urination and its discontents. AB - "Urination and Its Discontents" is an attempt to answer why various twentieth century artists have made works that use or are about urination. Andy Warhol's act of "pissing" onto a canvas in his Oxidation Paintings is related to homosexual "sex clubs," but also to the iconoclasm of Mapplethorpe, Serrano, Duchamp, and Pollock. Freud's idea that civilization began with the renunciation of the "homosexual competition" of urinating on the fire is discussed and compared to Ellis's idealization of the erotics of bodily functions. Weinberg suggests that artists follow Ellis instead of Freud in undermining the boundaries society places on what is clean and dirty and what is sexually permissible. PMID- 7798604 TI - Lesbian identity and the politics of representation in Betty Parsons's gallery. AB - Although Betty Parsons had been unusually open about her love relationships with women in the twenties and thirties, she later became reticent, retiring to the closet. Her increased discretion after World War II, during the Cold War, coincided with her rise as the art dealer most prominently associated with the international emergence of Abstract Expressionism. Parsons incurred the objections of her Abstract Expressionists, however, by showing artists who included both abstraction and naturalism in their work, such as Sonia Sekula, Forrest Bess, and Hedda Sterne. This article examines her definition of abstraction as difference through her friend Theodoros Stamos's notion of camp and helps to explain her admiration of Barnett Newman despite her refusal to devote her gallery exclusively to his narrower version of significant abstraction. PMID- 7798605 TI - Looking for love: a reading of Apartment Zero. AB - Asserting that gay male identity exists in the unstable frontier between culturally-defined notions of femininity and masculinity, this paper makes a close reading of the recent film Apartment Zero. This reading highlights the paradoxically aggressive and loving contest over the signs or trophies of masculinity--ranging from a soldier's cape to the phallus itself--which characterizes both homosocial and homosexual relations among men. Concluding that contrary to recent critical cliches, no subject can possess "the gaze," this paper describes the powerful desire to appropriate the signifiers of masculinity: a desire which can never be fully satisfied. PMID- 7798606 TI - Wear your hat: representational resistance in safer sex discourse. AB - Through an analysis of four posters used by the AIDS Action Committee of Massachusetts, this article asks how representation can effectively promote safer sex practices. The images under investigation have different targeted groups--one is aimed at African-American men, one at Latinas, and two at gay men. Using a frame-work that connects definitions of sex in the respective communities with differences surrounding gender, race, and class, the imagery is unpacked in order to expose the effects of safer sex representation. This essay then argues that the degree to which ingrained definitions of sex are challenged constitutes a determining factor in the success or failure of safer sex representations. PMID- 7798607 TI - Cruising twelfth-century pilgrims. AB - When taken together, the Moissac Luxuria, a miracle story from the Book of St. James, and the twelfth-century pilgrims who experienced them seem to show that sexual energy and an instability of gender characterized certain encounters among male pilgrims. I believe that this influenced what people saw when they looked at the Luxuria, and I try to situate this thesis in the context of Lesbian and Gay Studies. At the outset I adopt a "performative" view of homosexual relationships, and I close by relating the word "cruising" to the structural homology between myself and the people I study. PMID- 7798608 TI - Queering boundaries: semen and visual representations from the Middle Ages and in the era of the AIDS crisis. AB - In this essay I address some of the ways in which certain images, which share visual and verbal vocabularies of body fluids, visualize male-male sexual identities and body practices. Through the articulation of these terms, and most especially semen, body boundaries are at once delineated and transgressed. The differential relatedness of these images from the Middle Ages and the late 1980s and 1990s is underlined by the ways they subvert contemporary conventions of visual representation while always remaining accessible. It is this efficacy which allows me to link these representations, and which I attempt to articulate. To put this in other terms, I am interested in the ways in which boundaries of the body prove themselves fluid, as fluids of the body cross body-boundaries. PMID- 7798609 TI - Lesbian (in)visibility in Italian Renaissance culture: Diana and other cases of donna con donna. AB - Current conceptualizations of sexual identity in the West are not necessarily useful to an historian investigating "lesbianism" in the social history and visual representations of different periods. After an overview of Renaissance documents treating donna con donna relations which examines the potentially positive effects of condemnation and silence, the paper focuses on Diana, the goddess of chastity, who bathed with her nymphs as an exemplar of female bodies preserved for heterosexual, reproductive pleasures. Yet the self-sufficiency and bodily contact sometimes represented in images of this secluded all-female gathering might suggest "deviant" responses from their viewers. PMID- 7798610 TI - Genetic alterations in non-melanoma skin cancer. AB - Non-melanoma skin cancer is common and offers unrivaled opportunities to relate genetic changes to clinical and biologic behavior. Recent technical advances in molecular biology render genetic analysis of even the smallest skin cancers possible. In this review I will discuss the role of p53 gene in skin carcinogenesis, the relation between p53 immunostaining and p53 mutation, and recent evidence for the involvement of putative tumor suppressor genes both on chromosome 9 and other chromosomes in non-melanoma skin cancer. PMID- 7798611 TI - Selective accumulation of T cells according to T-cell receptor V beta gene usage in skin cancer. AB - To investigate whether specific T-cell populations are overrepresented in tumor infiltrating lymphocytes (TIL) in skin cancer, we determined the T-cell receptor (TCR) diversity in biopsy specimens of basal cell carcinoma and squamous cell carcinoma. Immunostaining of tissue sections indicated that the majority of T cells expressed alpha beta TCRs. To assess diversity of the TCR beta chain, RNA was isolated directly from the tumor specimens and peripheral blood mononuclear cells (PBMC) from the same patient, cDNA was synthesized, and variable (V) beta chain gene usage was determined by the polymerase chain reaction (PCR). In each basal cell (n = 11) and squamous cell (n = 7) carcinoma studied, several V beta families were overrepresented in TIL versus PBMC, in that they accounted for greater than 5% of the repertoire in TIL and were at least 2% higher in TIL than in PBMC. The predominant V beta gene segments overrepresented in TIL generally differed from individual to individual. Simultaneous comparison of the V beta repertoire of TIL to that of uninvolved skin and PBMC from the same individual revealed preferential expression of V beta families within the TIL in three of five basal cell and four of four squamous cell carcinomas. Again, the predominant V beta s differed from individual to individual. Comparison of the TCR repertoire in uninvolved skin versus PBMC did indicate that some V beta families were overexpressed in the resident T-cell compartment in skin, although the overrepresented families were not constant from individual to individual. These data indicate the selective concentration of T cells bearing specific alpha beta TCRs in the local immune response to basal cell and squamous cell carcinomas. PMID- 7798612 TI - Human leukocyte antigen-DQB1*03 alleles are associated with alopecia areata. AB - Alopecia areata (AA) is characterized by hair loss in patches (patchy AA), over the entire scalp (AT, totalis), or universally (AU). An autoimmune mechanism has been hypothesized, because the inflammatory infiltrate targeted to the hair follicles includes activated T cells. To investigate whether or not genetic polymorphism of the human leukocyte antigen (HLA) region contributes to disease susceptibility, we used sequence-specific oligonucleotides and amplified genomic DNA to define HLA-DQA1, -DQB1, and -DPB1 alleles in a cohort of 85 white patients. The frequency of DQB1*0301 was significantly increased to 41% in all patients, and to 47% in AT/AU patients relative to controls (27%). Analyzed together, DQB1*03 alleles (DQB1*0301-*0303) were increased to 80% (all patients) and to 92% (AT/AU) (odds ratio = 12.14, p = 0.00003, corrected). This striking association implicates the DQB1*03 alleles in the pathogenesis of AA. DQB1*06 was decreased relative to controls (56%) in all patients (32%, odds ratio = 0.37, p = 0.0045, corrected). An increase was observed in the HLA-DRB1*11(DR5) allele DRB1*1104, which may result from linkage disequilibrium with DQB1 alleles. Sequence comparison among the allele products associated with AA indicates that the DQB1*03 alleles carry a unique proline at position 55 that is not present in alleles that are neutral or negatively associated with the disease. This highly significant association may exert considerable control over immune responsiveness and the initiation or persistence of a T-cell autoimmune response against the hair follicle. PMID- 7798613 TI - Topical retinaldehyde on human skin: biologic effects and tolerance. AB - The present study was designed to explore if *etinaldehyde, a natural metabolite of vitamin A, has any biologic activity and is tolerated by human skin. Biologic activity was shown by the induction of cellular retinoic acid-binding protein type 2 (CRABP 2) mRNA and protein; the rank order for CRABP-2 increase was retinoic acid > retinaldehyde > 9 cis retinoic acid > retinol > beta carotene. In volunteers treated 1-3 months with 0.5, 0.1, and 0.05% retinaldehyde, there was a dose-dependent and significant increase in epidermal thickness, keratin 14 immunoreactivity, and Ki67-positive cells. The area of distribution of involucrin, transglutaminase, and filaggrin immunoreactivity was also increased in a dose-dependent manner, and keratin 4 immunoreactivity was induced in the upper epidermis. In pilot clinical tolerance studies, 229 patients received topical retinaldehyde at different concentrations; the 1% preparation was tolerated by up to 70% of the treated subjects; tolerance of the 0.5% preparation was slightly better, whereas both 0.1 and 0.05% preparations applied on facial skin were well tolerated and allowed prolonged use (up to 3 years) in patients with inflammatory dermatoses. These findings indicate that topical retinaldehyde has biologic activity and is well tolerated on human skin. PMID- 7798614 TI - Retinoic acid upregulates human Langerhans cell antigen presentation and surface expression of HLA-DR and CD11c, a beta 2 integrin critically involved in T-cell activation. AB - Immunomodulatory effects of retinoids may be part of their anti-carcinogenic and anti-inflammatory properties. We studied the in vivo effects of retinoic acid (RA) on antigen-presenting activity of human epidermal Langerhans cells and on accessory cell activity of keratinocytes. Two skin sites from each volunteer were treated in vivo with 0.1% RA or vehicle, respectively, once a day for 4 d. RA treated epidermal cell (RA-EC) alloantigen presentation to CD4+ T cells in each volunteer tested was consistently greater than that induced by vehicle EC. However, this increased antigen-presenting activity did not lead to autoreactive CD4+ T-lymphocyte proliferation. Elevated unfractionated epidermal antigen presenting activity of RA-EC was not due to increased keratinocyte major histocompatibility complex (MHC) or intercellular adhesion molecule expression or to other keratinocyte accessory signaling, because incubation of CD1a fluoroscence-activated cell sorter (FACS)-purified RA-EC inhibited alloantigen presentation, presumably through increased keratinocyte transforming growth factor-beta. By contrast, Langerhans cell function was upregulated; FACS-purified CD1a+ Langerhans cells derived from RA-EC displayed a markedly increased ability, relative to Langerhans cells from vehicle EC, to present alloantigen to T cells. Triple color flow-cytometric analysis of RA-EC and vehicle EC suspensions revealed that RA treatment did not modify the number of DR+ and CD1a+DR+EC, but did result in statistically significant increases in Langerhans cells expression of HLA-DR, CD11c, and CD1c. Another novel finding was that HLA-DR-dependent Langerhans cells antigen-presenting activity in both normal and RA-treated skin was completely blocked by anti-CD11c antibody. Thus, retinoid upregulation of antigen-presenting activity may be due to upregulation of Langerhans cell CD11c, as well as class II MHC. Upregulation of cutaneous immune responsiveness in human skin without autoreactivity has not (to our knowledge) been reported previously, and the Langerhans cell phenotypic and functional state achieved is distinct from previously reported states of Langerhans cell activation. PMID- 7798615 TI - Epidermal differentiation enhances CRABP II expression in human skin. AB - The cellular retinoic acid-binding proteins (CRABP I and II) are thought to mediate the effects of retinoic acid on target cells. We have used riboprobes complementary to CRABP I and II mRNAs to study the expression of these messages in normal and abnormal human skin. CRABP II was expressed predominantly in the suprabasal layers of the epidermis, with stronger expression in newborn than in sun-protected adult skin. Interestingly, the epidermis adjacent to or overlying squamous cell or basal cell carcinomas also showed strong expression, whereas the tumor cells were negative, with the exception of more differentiated cells surrounding the "keratin pearls" within squamous cell carcinomas. CRABP II mRNA was also found in the more differentiated cells of the hair follicles, in the outer root sheath. CRABP I message was undetectable in the epidermis or in the dermis of normal skin but was detected in the cells of the papillary dermis surrounding basal and squamous cell carcinomas. These data suggest that increased levels of CRABP II mRNA accompany keratinocyte differentiation in vivo. PMID- 7798616 TI - Suppressive effect of antioxidants on intercellular adhesion molecule-1 (ICAM-1) expression in human epidermal keratinocytes. AB - Intercellular adhesion molecule-1 (ICAM-1) is strongly expressed by human epidermal keratinocytes during the course of inflammatory skin diseases. To test the possibility that reactive oxygen species produced in the skin during an inflammatory response affect ICAM-1 expression, cultured human epidermal keratinocytes were treated with H2O2 at concentrations that did not damage the cells, and cell-surface ICAM-1 expression was analyzed. Expression of ICAM-1 was induced on keratinocytes by treatment with 300 microM H2O2 for 1 h. The antioxidant N-acetyl-L-cysteine strongly inhibited H2O2-induced ICAM-1 expression, whereas the antioxidants pyrrolidine dithiocarbamate and alpha tocopherol were less inhibitory. N-acetyl-L-cysteine also suppressed keratinocyte surface expression of ICAM-1 induced by the cytokines interferon-gamma (IFN gamma) or tumor necrosis factor-alpha (TNF-alpha), whereas pyrrolidine dithiocarbamate and alpha-tocopherol suppressed IFN-gamma-induced surface expression but not TNF-alpha-induced expression. We found that N-acetyl-L cysteine treatment reduced ICAM-1 mRNA levels when keratinocytes were stimulated with either IFN-gamma or TNF-alpha; however, pyrrolidine dithiocarbamate and alpha-tocopherol had no effect on either IFN-gamma- or TNF-alpha-induced ICAM-1 mRNA levels. Our results indicate that reactive oxygen species may be involved in the skin inflammatory process by increasing epidermal ICAM-1 expression and that some antioxidants may be effective in suppressing the epidermal ICAM-1 expression induced by reactive oxygen species and cytokines in inflammatory skin diseases. PMID- 7798617 TI - Experimental photoaging in C3H/HeN, C3H/HeJ, and Balb/c mice: comparison of changes in extracellular matrix components and mast cell numbers. AB - Chronic exposure of human or murine skin to ultraviolet B (UVB) radiation alters dermal extracellular matrix composition and increases the number of mast cells and inflammatory cells. Experiments were designed to test the possible role of UVB-induced tumor necrosis factor-alpha in these photoaging changes based on reports that C3H/HeN, but not C3H/HeJ or Balb/c mice, produce excess TNF-alpha in response to UVB exposure. Pigmented C3H/HeN and C3H/HeJ strains were exposed to a total of 75 J/cm2 of UVB radiation, and unpigmented Balb/c mice were exposed to 19 J/cm2. The UVB-induced increases in collagen, glycosaminoglycans, and neutrophil number were similar or the same in all three strains. The elastin increase was greater in C3H/HeJ than in C3H/HeN mice. The most striking difference between the strains was a 7.7-fold UVB-induced increase in mast cells in C3H/HeN mice compared to no increase in irradiated C3H/HeJ mice and a 2.3-fold increase in Balb/c mice. These results suggest that excess TNF-alpha (or other mediator) produced in C3H/HeN skin (but not C3H/HeJ skin) in response to UVB exposure is involved in the mast cell increase and partial inhibition of elastin increase, but that neither these mediators nor mast cell products are important mediators for the chronic UVB-induced increases in neutrophils, glycosaminoglycans, and collagen. When a possible source of the excess TNF-alpha was investigated, it was found that isolated epidermal cells from all three strains produced increases in TNF-alpha in response to UVB radiation. These results, as well as the previous results showing differences between these strains in UVB-induced effects on cutaneous immune function, are consistent with a model in which UVB-induced mediators from the epidermis stimulate another cell type to produce excess TNF-alpha (and other mediators) in the C3H/HeN but not C3H/HeJ or Balb/c mice. PMID- 7798618 TI - Differential photoimmunoprotection by sunscreen ingredients is unrelated to epidermal cis urocanic acid formation in hairless mice. AB - A series of experimental sunscreen preparations based on a common vehicle, containing increasing concentrations of either octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC) as the ultraviolet B (UVB) absorber, has been tested in the hairless mouse for the ability to protect from erythema, from the systemically suppressive effects of UVB (280-320 nm) radiation on contact hypersensitivity, and from photoisomerization of epidermal urocanic acid. All the preparations protected efficiently from the edema component of the erythema response when mice were exposed to UVB radiation equivalent to three times the minimal erythema dose (MED). However, when mice were exposed to UVB radiation equivalent to 15 x MED, protection from erythema was observed only at the higher concentrations of each UVB absorber (10% 2-EHMC and 10% or 15% o PABA). Protection from the UVB-induced suppression of contact hypersensitivity was shown to be dependent on both the nature of the UVB absorber and its concentration. Photoimmunoprotection by the sunscreens containing 2-EHMC was evident at lower concentrations (5% and 10% 2-EHMC) than with o-PABA, following both 3 x MED and 15 x MED of UVB exposure. Photoimmunoprotection by o-PABA containing sunscreens was observed only at 15% o-PABA following 3 x MED, and failed at all tested concentrations after 15 x MED of UVB exposure. Regardless of the photoimmunoprotective capacity, sunscreen preparations containing either of the UVB absorbers prevented the UVB-induced formation of cis urocanic acid in the mouse epidermis and in vitro under all conditions tested. Thus, there appeared to be a correlation between protection from edema and from cis urocanic acid formation at 3 x MED of UVB, but a dissociation of these variables at 15 x MED of UVB. There was no relation apparent at either UVB dose between either edema or cis urocanic acid formation and protection from suppression of contact hypersensitivity. PMID- 7798619 TI - Functional human epidermal Langerhans cells that lack Birbeck granules. AB - Birbeck granules (BG) are cytoplasmic organelles that are only found in Langerhans cells (LC). The function of BG is still unclear, although it has been claimed that they are actively involved in receptor-mediated endocytosis and participate in the antigen-processing/presenting function of LC. We have identified a healthy white 29-year-old man whose LC completely lack the presence of BG as determined by electronmicroscopic studies. This was observed repeatedly using skin biopsy specimens taken from several places on the body during a period of 2.5 years. The absence of BG in these LG was documented further by the lack of staining with a BG-specific monoclonal antibody. Despite the complete lack of BG, LC were present in normal numbers, had all the usual morphologic characteristics, and were CD1a and human leukocyte antigen (HLA) class II positive. Two observations indicate that these BG-negative LC display normal antigen-presenting capacity. First, the individual could be sensitized by the hapten diphenylcyclopropenone. This was accompanied by a strong increase in the cell surface expression of HLA class II antigens on his LC, suggesting LC activation. Second, his epidermal cells elicited a normal positive response in an allogeneic mixed epidermal cell lymphocyte reaction. Together these observations strongly suggest that BG are not a prerequisite for normal LC function in vivo and in vitro. PMID- 7798620 TI - Interleukin-10 inhibits the elicitation phase of allergic contact hypersensitivity. AB - Interleukin-10 (IL-10) is known to play a major role in suppressing immune and inflammatory responses by inhibiting the production of proinflammatory cytokines. Therefore, we hypothesized that IL-10 might be capable of suppressing allergic contact hypersensitivity. BALB/c mice were sensitized on the dorsal skin with dinitrofluorobenzene and challenged on the ears 6 d later. The effect of IL-10 on the elicitation phase of contact sensitization was determined by its intradermal injection into the pinnae of the mice at doses of 0.1-100 ng. At 24 and 48 h after challenge, ear swelling was suppressed in a dose-dependent manner by injection of IL-10 at doses of 10-100 ng. Maximal inhibition of ear swelling (46.9%) was observed after injection of 100 ng of IL-10. IL-10-injected ear skins showed less inflammatory cell infiltration and decreased edema at the dermis compared with controls. Because IL-10 is known to inhibit Th1 cytokines such as interferon-gamma, we examined whether the suppressive effect of IL-10 on ear swelling was accompanied by IL-10-induced inhibition of interferon-gamma. We found that IL-10 application suppressed interferon-gamma mRNA upregulation in challenged skin. Our results suggest that IL-10 significantly modifies the elicitation of allergic contact sensitivity reactions. PMID- 7798621 TI - Involucrin mRNA is more abundant in human hair follicles than in normal epidermis. AB - Involucrin is a precursor protein of the cornified cell envelope in epidermal keratinocytes, where it has been located by immunohistochemistry in the upper spinous and granular layers of human epidermis. In the hair follicle, involucrin has been found in the inner root sheath and in the upper layers of the infundibulum and the isthmus (upper outer root sheath), whereas its presence in the lower outer root sheath and the cortex has been controversial. Therefore, we analyzed the distribution of involucrin mRNA in adult scalp by Northern blotting and in situ hybridization. Northern blots showed more abundant involucrin mRNA in the follicular fraction than in the epidermal fraction of dissected scalp. In situ hybridization matched the immunohistologic results; transcripts of involucrin were expressed not only in the infundibulum and isthmus, but also in the hair cortex and medulla, in all layers of the inner root sheath, and in the inner cells of the lower outer root sheath (all of which lack a cell envelope at the ultrastructural level). However, involucrin was absent in the hair cuticle, which is the only compartment of the follicle possessing a morphologically distinct cell envelope. Our results suggest, first, that involucrin does not serve as a precursor protein of the cornified cell envelope in adult hair follicles, and second, that it is perhaps not necessary for the formation of the cell envelope in keratinocytes of the hair cuticle, as we did not find this precursor protein with highly sensitive methodology. PMID- 7798622 TI - Functional and immunoreactive thrombomodulin expressed by keratinocytes. AB - In an immunohistopathologic study using two monoclonal antibodies that recognize independent epitopes on human thrombomodulin, we detected expression of thrombomodulin on Malpighian-layer keratinocytes, but not on the basal or upper granular-layer keratinocytes. Western blotting and thrombomodulin-specific enzyme linked immunosorbent assay performed on both shaved skin and cultured SV40 transformed keratinocytes showed the expression of full-length thrombomodulin, indistinguishable from endothelial thrombomodulin. Thrombomodulin was expressed by keratinocytes in 1 mM calcium but not in reduced calcium. A functional assay for thrombomodulin revealed that epidermal-derived thrombomodulin possessed cofactor activity for thrombin-catalyzed protein C activation. The limited pattern of expression of thrombomodulin in epidermis implies that this molecule may be a differentiation marker of keratinocytes in addition to being a potent anticoagulant in the skin. PMID- 7798623 TI - Abnormal Bcl-2 and "tissue" transglutaminase expression in psoriatic skin. AB - Cell death by apoptosis plays a key role in skin development and homeostasis. Previous studies have shown that increased apoptosis characterizes several pathologic conditions affecting human skin. Thus, the pathogenesis of cutaneous diseases may involve an imbalance in the homeostatic mechanisms determining whether the death of keratinocytes will occur by terminal differentiation or apoptosis. We investigated the involvement of apoptosis in psoriasis. For this purpose, we assessed, in addition to morphology and DNA fragmentation, the expression of two putative apoptotic genes, bcl-2 and "tissue" transglutaminase, in normal and psoriatic skin. A large number of keratinocytes showing biochemical and morphologic features of cells undergoing apoptosis was observed in all the suprabasal layers of the psoriatic epidermis. The plaques from all patients analyzed showed a dramatic reduction in the number of bcl-2-positive cells localized in the basal cell compartment. In contrast, the psoriatic lesions presented a marked induction in "tissue" transglutaminase, which was localized specifically to the cytoplasm of apoptotic keratinocytes. "Tissue" transglutaminase protein staining was undetectable in normal epidermis. The bcl-2 and "tissue" transglutaminase staining pattern observed in psoriasis also was found in the skin of patients affected by lichen planus. These findings indicate that these two genes are regulated in an opposite fashion in psoriatic keratinocytes undergoing apoptosis, thus confirming their antithetic role in the cascade of events leading to the establishment of the mature apoptotic phenotype. PMID- 7798624 TI - Occlusion lowers cytokine mRNA levels in essential fatty acid-deficient and normal mouse epidermis, but not after acute barrier disruption. AB - Acute disruption of the permeability barrier by either tape stripping or acetone treatment and chronic disruption by feeding an essential fatty acid-deficient diet increase the mRNA levels of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1 alpha, IL-1 beta, IL-1ra, and granulocyte/macrophage-colony stimulating factor in murine epidermis. Furthermore, epidermal TNF alpha protein levels also are stimulated by barrier disruption. To understand the relation of epidermal cytokine production to barrier function, we studied the effect of the application of a water vapor-impermeable membrane on epidermal cytokine production both in normal epidermis and after barrier disruption. Latex occlusion of essential fatty acid-deficient mice for 24-48 h lowered the mRNA levels of epidermal TNF alpha, IL-1 alpha, and IL-1ra to nearly control values, but not the levels of IL-1 beta mRNA. Occlusion of normal mice for 8, 24, and 48 h did not alter the levels of epidermal mRNAs encoding TNF alpha, IL-1 beta, or IL-1ra. Yet mRNA levels of IL-1 alpha, the major constitutively produced epidermal cytokine, were reduced by 40% after 24 h and by 80% after 48 h of occlusion of normal mouse epidermis. In contrast, latex occlusion of mice immediately after acute barrier disruption by either tape stripping or acetone treatment blocked neither the stimulation of epidermal mRNAs for TNF alpha, IL-1 alpha, IL-1 beta, or IL-1ra, nor the increase in epidermal TNF alpha protein. Taken together, these results suggest that barrier status regulates the production of specific cytokines in essential fatty acid-deficient and normal mouse epidermis. However, the signals that regulate epidermal cytokine production in response to acute barrier disruption do not appear to be influenced by occlusion. PMID- 7798625 TI - International symposium on epidermolysis bullosa. The William and Ida Friday Continuing Education Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, April 25-26, 1994. Abstracts. AB - An international symposium on inherited epidermolysis bullosa was held at the University of North Carolina at Chapel Hill on April 25-26, 1994. All areas currently of clinical and research interest pertinent to this disease were discussed, ranging from basic epidemiologic issues to the definition of molecular defects in each of the three major types of epidermolysis bullosa and the potential for gene therapy. A major focus of this meeting was the presentation of data collected by the National Epidermolysis Bullosa Registry. PMID- 7798626 TI - Use of a serum-free epidermal culture model to show deleterious effects of epidermal growth factor on morphogenesis and differentiation. AB - The presence of serum has limited the utility of many culture models for the study of cytokine effects because its complexity and variability can confound the interpretation of data. In the present study, a serum-free skin co-culture model was used to investigate the effect of exogenous epidermal growth factor (EGF) on epidermal proliferation and differentiation. Human keratinocytes cultured on collagen rafts at the air-liquid interface produced a well-differentiated epithelium that resembled normal epidermis. Keratin filaments, membrane-coating granules, and keratohyalin granules were all observed. Epidermal differentiation markers keratin K1/K10, involucrin, and transglutaminase were localized in most of the suprabasal layers, whereas profilaggrin/filaggrin was confined to the granular layers and stratum corneum. In the continual presence of 10-20 ng/mL EGF, the epidermis was less organized, thinner, and less proliferative. EGF also depressed several indicators of differentiation: The number of keratohyalin granules and membrane-coating granules was greatly decreased; antigen expression of profilaggrin/filaggrin appeared diminished by immunocytochemical staining; frequent nuclear retention was noted in the relatively thickened stratum corneum like layers. As detected by immunohistochemical staining, the expression of EGF receptor in the epidermis was reduced by exogenous EGF. These data illustrate that EGF cannot be considered a simple mitogen. Our findings also underscore the importance of using sophisticated culture models to assess complex cytokine effects that may be dependent on the architecture of a differentiating epidermis. PMID- 7798627 TI - Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates. AB - Prior studies of mouse skin in organ culture have shown that dendritic cells selectively emigrate from the explants over 1-3 d. This emigration may model the movements of dendritic cells that can occur in situ, as in transplantation and contact sensitivity. In this study, we cultured explants of normal human skin that had been removed with a dermatome. Dendritic cells with characteristic morphology and mixed leukocyte response-stimulatory activity emigrated. The dendritic cells had the expected phenotype, e.g., rich in major histocompatibility complex class II and accessory molecules such as B7-1, intercellular adhesion molecule-1, and leukocyte function-associated antigen-3. Small lymphocytes also were present in the emigrated populations and proved to be T cells exclusively, almost entirely of the TcR alpha beta and memory type (CD45RAweak, CD45RO LFA-3/CD58+), with a CD4:CD8 subset ratio of about 2:1. Some of the T cells were bound tightly to the dendritic cells. These conjugates did not dissociate after exposure to trypsin or to calcium- and magnesium-free medium, or during cytofluorography. This made it possible to sort distinct populations of single dendritic cells, single T cells, and conjugates of the two cell types. Conjugates would continue to form from mixtures of separated dendritic cells and T cells in culture. Therefore, cutaneous dendritic cells and memory T lymphocytes emigrate from human skin explants, and some of these cells form distinctive conjugates that we hypothesize contribute to immunologic recall reactions. PMID- 7798628 TI - The antiproliferative and differentiative activities of 1,25-dihydroxyvitamin D3 are potentiated by epidermal growth factor and attenuated by insulin in cultured human keratinocytes. AB - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent inhibitor of keratinocyte proliferation, as well as a stimulator of epidermal terminal differentiation. In the present studies, we investigated the influence of epidermal growth factor (EGF) and insulin on the antiproliferative and differentiation activities of 1,25(OH)2D3. Our results indicate the following: (1) EGF caused a dramatic potentiation of the 1,25(OH)2 D3-induced inhibition of 3H-thymidine incorporation into keratinocytes in a dose-dependent manner; (2) insulin acted antagonistically on the EGF-dependent potentiation of the 1,25(OH)2D3-induced antiproliferative activity; (3) transforming growth factor-alpha potentiated 1,25(OH)2D3-induced antiproliferative activity similar to EGF; (4) the EGF effect was not dependent upon 1,25(OH)2D3 receptor mRNA up-regulation; and (5) removal of insulin from medium supplemented with growth factors significantly potentiated the 1,25(OH)2D3 induced inhibition on the number of basal cells and the 1,25(OH)2D3-dependent cornified envelope formation. In conclusion, the antiproliferative activity of 1,25(OH)2D3 in cultured normal human keratinocytes is greatly enhanced by EGF or transforming growth factor-alpha and reduced by insulin. Insulin also inhibits 1,25(OH)2D3-induced terminal differentiation of cultured normal human keratinocytes. PMID- 7798629 TI - Different effects of basic fibroblast growth factor and transforming growth factor-beta on the two platelet-derived growth factor receptors' expression in scleroderma and healthy human dermal fibroblasts. AB - Previous studies have demonstrated that platelet-derived growth factor (PDGF) alpha receptor expression is up-regulated by transforming growth factor-beta 1 (TGF-beta 1) in scleroderma dermal fibroblasts, but not in healthy control fibroblasts. We asked whether this selective effect in scleroderma cells was TGF beta 1-specific or a general response by studying responses to other growth factors. In this study, we compared the expression of alpha and beta PDGF receptor subunits (mRNA and protein levels) in these two cell types in response to basic fibroblast growth factor (bFGF) and TGF-beta 1. bFGF coordinately stimulated mRNA levels of alpha and beta receptor subunits in healthy fibroblasts, but did not change PDGF receptor expression in scleroderma fibroblasts. Conversely, and in agreement with previous observations, TGF-beta 1 induced PDGF alpha receptor expression in scleroderma fibroblasts, but not in healthy fibroblasts. PDGF beta receptor mRNA levels were induced to similar degrees by TGF-beta 1 in both cell types. PDGF alpha receptor protein levels correlated directly with mRNA levels, induced by bFGF only in healthy fibroblasts and by TGF-beta 1 only in scleroderma fibroblasts. However, PDGF beta receptor protein levels were not altered by either growth factor in either cell type. Thus, the activated state of scleroderma fibroblasts does not include receptor signaling pathways to bFGF. This distinct pattern of expression of PDGF alpha receptors in scleroderma fibroblasts suggests a possible role for the coordinately expressed PDGF AA ligand/alpha receptor system in the development of fibrosis. PMID- 7798630 TI - Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts. AB - It is thought that normal fibrotic repair progresses to dermal fibrosis when fibroblasts are activated persistently by chronic exposure to cytokines such as transforming growth factor-beta. However, additional cytokines and mechanisms may play a role in the development of fibrosis. Thus, we examined a recently described T-lymphocyte/macrophage-derived cytokine, oncostatin M, for its effect on the production of collagen and glycosaminoglycan by microcultures of normal dermal, sclerodermal, and keloidal fibroblasts. Treatment with oncostatin M for 48 h induced dose-dependent (1-100 ng/ml) increases in the collagen and glycosaminoglycan production of nine normal fibroblast strains, which in the absence of fetal bovine serum at 100 ng/ml averaged 196% and 244%, respectively. Oncostatin M treatment increased both types I and III procollagens and their mRNA transcripts, as well as levels of hyaluronic acid, chondroitin-4/6 sulfates, and dermatan sulfate, but not fibronectin or general noncollagenous protein synthesis. In contrast, the collagen production of six of eight sclerodermal and keloidal fibroblast strains was essentially unresponsive to oncostatin M treatment, with 100 ng/ml inducing an average increase of only 34% for the eight fibrotic strains. Oncostatin M stimulation of fibrotic fibroblast glycosaminoglycan production was also hyporesponsive, as 100 ng/ml of oncostatin M induced an average increase of only 101%. These results indicate that oncostatin M could function as a stimulator of normal fibrotic repair via activation of fibroblast collagen and glycosaminoglycan synthesis and that the persistent activation of sclerodermal and keloidal fibroblasts is accompanied by a loss of sensitivity to oncostatin M stimulation. PMID- 7798631 TI - Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis. AB - To prove the existence of human intraepidermal nerve fibers at the electron microscopic level, we used both conventional and immunohistochemical ultrastructural techniques. Specimens were obtained from skin of the back, one of the most densely innervated areas of the human epidermis. The immunohistochemical marker protein gene product 9.5 was chosen because it is highly potent in labeling nerves. Thin nerve fibers were found in the basal, spinous, and granular layers of the epidermis with both techniques used, although it was more difficult to identify the nervous structures with the conventional method. The nerves appeared in the intercellular spaces and contacted keratinocyte cell bodies or cilia by membrane-membrane apposition, but without any specialized structures. Nerve fibers in the very superficial part of the vital human epidermis have not been described before at the ultrastructural level. PMID- 7798632 TI - Antibodies to the E4, E6, and E7 proteins of human papillomavirus (HPV) type 16 in patients with HPV-associated diseases and in the normal population. AB - In a cross-sectional study, titers of antibodies to the E4 and E7 proteins of human papillomavirus (HPV) type 16 were measured by peptide-based enzyme-linked immunosorbent assay in 1707 sera. Sera were obtained from healthy individuals (ages 1 to 95 years), from patients with HPV-associated infection (cervical intraepithelial neoplasia and cervical cancer), and from patients who were at high risk for HPV infection (attending a sexually transmitted disease clinic or referred to a colposcopist because of an abnormal Papanicolaou smear). The prevalence of anti-E7 antibodies increased with age, although the overall prevalence in the adult population was low (10.36%) compared to the frequent detection of HPV 16 DNA in the population. This suggests that only a fraction of patients infected with HPV 16 develop an anti-E7 response. The age distribution of anti-E4 antibodies showed a different pattern, i.e., the prevalence was low in the adult population (1.14%) but exceeded 20% in children and teenagers. As the specificity of the anti-E4 reaction was supported by a highly significant association with anti-E6 positivity in children's sera (p = 0.002), it was assumed that infection with HPV 16 can occur frequently early in life. As compared to healthy controls, patients at high risk for HPV infection had a significantly higher frequency (p < 0.001) of antibodies to the HPV 16 E4 protein (but not to the E6 or the E7 protein) in their sera. Therefore, we conclude that in adults E4-specific antibodies may be a marker for virus replication. PMID- 7798633 TI - Direct imaging of molecular transport through skin. AB - Scanning electrochemical microscopy (SECM) was used to image spatial variations in the molecular flux of Fe(CN)6(-4) across excised hairless and nude mouse skin. The SECM response is specific to electroactive molecules, allowing selective imaging of the flux of Fe(CN)6(-4) in multicomponent ionic solutions. Quantitative SECM image analysis demonstrated that 40% to 60% of the total Fe(CN)6(-4) flux occurred through appendages in the skin. SECM analysis of skin samples exposed to a known transport enhancer, sodium dodecylsulfate, indicated that the increase in the ion transport rate occurred exclusively in nonporous skin tissue. PMID- 7798634 TI - Adhesion molecules. I: Keratinocyte-keratinocyte interactions; cadherins and pemphigus. AB - During the last few years, considerable progress has been made in our understanding of the structure and function of cadherins and of the pathophysiology of pemphigus. Cadherins are a multiple gene family of Ca(++) dependent cell adhesion molecules with a typical single-spanning transmembrane structure. Cadherins have two major subfamilies, classic cadherin and desmosomal cadherin. Classic cadherins, including E-, P-, and N-cadherins, are characterized by a homophilic binding specificity. They localize at adherens junctions and mediate physiologic interaction with the involvement of cytoplasmic anchoring molecules, catenins, and the actin-based cytoskeleton network. Desmosomal cadherins, the desmocollins and desmogleins, localize at desmosomes and are linked to the intermediate keratin filaments network via plakoglobin and desmoplakin. Molecular cloning has demonstrated that the autoantigens of both pemphigus vulgaris and pemphigus foliaceus are members of the desmoglein subfamily of the cadherin supergene family. Thus, pemphigus is characterized as an anti-cadherin autoimmune disease. Furthermore, a baculovirus recombinant protein of pemphigus vulgaris antigen was capable of absorbing out the pathogenic autoantibodies from patients' sera, providing a possibility of antigen-specific therapeutic strategies for pemphigus. PMID- 7798635 TI - Suppressive and enhancing effects of ultraviolet B radiation on expression of contact hypersensitivity in man. AB - Ultraviolet B (UVB) radiation has multiple effects on the immune system, and these effects contribute to the development of UVB-induced skin cancers in mice, and probably man. Depending upon dose and duration of UVB exposure, the resultant immune aberrations may be strictly local (at the irradiated skin site) or systemic. One important local effect of acute, low-dose UVB regimens is impaired induction of contact hypersensitivity (CH). Because a significant proportion of humans who develop CH when hapten is painted on UVB-exposed skin fall to display a primary allergic reaction at that site, we inquired into the effects of UVB radiation on the expression of CH in man. A high proportion of individuals who were first exposed to a sensitizing dose of hapten via UVB-exposed skin displayed CH when challenged on unirradiated (normal) skin 11 d later. However, only 50% of these subjects developed CH when challenged simultaneously on skin that had been exposed to UVB radiation 11 d previously. Because the density of epidermal antigen-presenting cells was comparable in both responders and non-responders, we interpret these findings to mean that UVB radiation can create a sustained immunosuppressive microenvironment that inhibits the expression of CH. In separate experiments, when normal volunteers were sensitized with hapten via unirradiated (normal) skin, expression of CH at UVB-exposed challenge sites 11 d later was found to be enhanced, at least in some individuals, compared to expression of CH at unirradiated challenge sites. Thus, the local effects of UVB radiation on expression of CH in man may be enhancing or inhibitory, depending upon whether initial sensitization occurred through normal or through UVB-exposed skin. PMID- 7798636 TI - No evidence for Borrelia burgdorferi-specific DNA in lesions of localized scleroderma. AB - A possible association of Borrelia burgdorferi with localized scleroderma is currently the focus of intense research and discussion. Skin biopsies from 30 patients with localized scleroderma (28 of the plaque type/morphea; two linear scleroderma) were analyzed for the presence of Borrelia burgdorferi using three different polymerase chain reaction systems for amplification of segments of borrelial genes. Formalin-fixed, paraffin-embedded biopsies of 14 patients and fresh-frozen, cryo-conserved biopsies of 16 patients with localized scleroderma were obtained. Lesions of all patients showed clear signs of scleroderma and disease progression at the time of biopsy. Fresh-frozen as well as formalin-fixed biopsies from patients with erythema migrans or acrodermatitis chronica atrophicans were used as positive controls. With all three polymerase chain reaction systems, borrelial DNA was detected in none of the 30 specimens of localized scleroderma. In contrast, with one polymerase chain reaction system, Borrelia burgdorferi-specific DNA was found in 24 of 27 frozen biopsies from patients with erythema migrans and in all 5 analyzed frozen biopsies of patients with acrodermatitis chronica atrophicans. In approximately half of the paraffin embedded biopsies from patients with erythema migrans (nine of 23) and acrodermatitis chronica atrophicans (13 of 27), Borrelia burgdorferi-specific DNA was identified. These results question the association of localized scleroderma with known subtypes of Borrelia burgdorferi. PMID- 7798637 TI - Interleukin-10 production by cultured human keratinocytes: regulation by ultraviolet B and ultraviolet A1 radiation. AB - Keratinocytes are the primary cellular target for ultraviolet radiation in human skin, and ultraviolet radiation-induced therapeutical effects may thus be mediated by keratinocyte-derived, antiinflammatory mediators. Interleukin-10 is capable of exerting antiinflammatory effects by virtue of its capacity to suppress the production of interferon-gamma. The present study therefore assessed the ability of cultured human keratinocytes to produce interleukin-10 following ultraviolet irradiation. Exposure of long-term cultured normal human keratinocytes to ultraviolet B (280-320 nm) or to ultraviolet A1 (340-400 nm) radiation caused a time- and dose-dependent induction of interleukin-10 mRNA expression and interleukin-10 protein secretion, with ultraviolet A1 radiation being the strongest stimulus. Ultraviolet radiation-induced interleukin-10 production by normal human keratinocytes was enhanced by a factor of two, when cells were cultured in high- rather than low-calcium medium. Neither addition of the ultraviolet radiation-inducible cytokines tumor necrosis factor-alpha or interleukin-1 alpha to unirradiated keratinocytes nor presence of their respective neutralizing antibodies in cultures of irradiated keratinocytes induced or inhibited interleukin-10 synthesis. Modulation of eicosanoid production by addition of prostaglandin E2 to keratinocyte cultures or disturbance of cyclooxygenase activity by indomethacin did not affect interleukin 10 production in resting or irradiated cells. These studies demonstrate that cultured human keratinocytes are capable of producing interleukin-10. Human keratinocyte interleukin-10 production is dependent on the differentiation state of the cell and induced by ultraviolet B and, in particular, ultraviolet A1 radiation exposure. This novel property of ultraviolet radiation may account at least in part for the efficacy of phototherapy in inflammatory skin diseases. PMID- 7798638 TI - Pemphigus IgG, but not bullous pemphigoid IgG, causes a transient increase in intracellular calcium and inositol 1,4,5-triphosphate in DJM-1 cells, a squamous cell carcinoma line. AB - It is still unclear what kinds of mechanisms are involved in blister formation after antibodies bind to the antigens in pemphigus and bullous pemphigoid. The effects of IgGs from pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid sera on intracellular calcium concentration ([Ca++]i) and inositol 1,4,5-trisphosphate were examined in a human squamous cell carcinoma cell line (DJM-1 cells) and in cultured human keratinocytes to clarify whether signal transduction via calcium is involved. IgGs were purified with protein A affinity column from the sera of five pemphigus vulgaris patients, three pemphigus foliaceus patients, eight bullous pemphigoid patients, and 14 normal volunteers. Keratinocytes were cultured in Eagle's minimum essential medium containing 1.8 mM Ca++ and loaded with fura-2/AM, followed by addition of the IgGs. Subsequently, [Ca++]i was determined by measuring the fluorescence ratio (F340/F360) with videomicroscopy. Pemphigus IgGs (seven of eight cases) induced a rapid and transient increase in [Ca++]i in both the cells, whereas a [Ca++]i increase was caused by very few IgGs from bullous pemphigoid (one of eight cases) and normal sera (two of 14 cases). The pemphigus IgG-induced transient [Ca++]i increase was not affected by chelating extracellular Ca++ with ethyleneglycol-bis(beta aminoethyl ether)-N,N,N',N'-tetracetic acid. In addition, monoclonal antibodies acid. In addition, monoclonal antibodies against 180-kD and 230-kD antigens did not exert this change. Pemphigus IgGs that caused a [Ca++]i increase induced rapid and transient production of inositol 1,4,5-trisphosphate, peaking at 20 seconds. These findings suggest that IgG from pemphigus induces Ca++ mobilization by inositol 1,4,5-trisphosphate from internal stores, and that mechanisms of antibody-transmitted signaling in pemphigus may differ from those in bullous pemphigoid. PMID- 7798639 TI - Structure-function relations in the inhibition of murine contact hypersensitivity by amiloride. AB - Topical application of amiloride, a potent inhibitor of the Na+/H+ antiport, inhibits cutaneous inflammation induced by ultraviolet radiation or contact hypersensitivity in mice. Amiloride analogues with greater and lesser inhibition of the Na+/H+ exchange were tested to determine whether anti-inflammatory effects correlate with this activity. Structural analogues of amiloride without significant activity at the Na+/H+ antiport (pyrazine, pyrazinamide, and chloropyrazine) failed to inhibit contact hypersensitivity. N-amidino-3-amino-5 dimethyl amino-6-chloropyrazinecarboxamide (DMA) has a 23-fold greater affinity for the Na+/H+ antiport compared to amiloride, but failed to inhibit contact hypersensitivity in this assay. 3,5-diamino-6-chloropyrazine-amido-guanidine (DCG), which has only 7% of the affinity of amiloride for the antiport, suppressed contact hypersensitivity as well as amiloride. Experiments examining the ability of these agents to diffuse through mouse skin revealed amiloride to be superior to both DCG and DMA, which were approximately equal. DMA, with greater inhibition of the Na+/H+ antiport but lesser ability to inhibit contact hypersensitivity, inhibited protein synthesis and induced cell death more than amiloride or DCG. Amiloride and DCG hold promise as topical anti-inflammatory agents. Their anti-inflammatory properties do not correlate with affinity for the Na+/H+ antiport, ability to penetrate murine skin, or inhibition of protein synthesis. PMID- 7798640 TI - Enhancement of delayed hypersensitivity inflammatory reactions in guinea pig skin by 12(R)-hydroxy-5,8,14-eicosatrienoic acid. AB - Delayed-type hypersensitivity (DTH) reactions are initiated by sensitized T cells. Their progression is dependent upon the local release of various autacoids, including cytokines and eicosanoids, by T cells, infiltrating inflammatory cells, and resident tissue cells. 12(R)-hydroxy-5,8,14 eicosatrienoic acid [12(R)-HETrE], an eicosanoid produced by skin and cornea, possesses potent proinflammatory properties at picomolar concentrations including vasodilation, increase in membrane permeability, neutrophil chemotaxis, and angiogenesis. Because DTH reactions are associated with many of these same phenomena, we examined the effect of 12(R)-HETrE and related 12 hydroxyeicosanoids on the expression of DTH to purified protein derivative of tuberculin in sensitized guinea pigs. In the absence of purified protein derivative of tuberculin, none of the eicosanoids evoked erythema or edema after intradermal injection at doses up to 100 pmol. When injected together with purified protein derivative of tuberculin, 12(R)-hydroxy-5,8,10,14 eicosatetraenoic acid [12(R)-HETE], but not its enantiomer 12(S)-HETE, significantly inhibited macroscopic expression of delayed reactivity (erythema) only at the highest dose tested, 10 pmol. In contrast, 12(R)-HETrE significantly enhanced expression of DTH at doses between 1 fmol and 1 pmol (50% and 30% increases above control, respectively). Its stereoisomer, 12(S)-HETrE, did not enhance DTH at any tested dose, but was able to block the activity of 12(R)-HETrE when injected simultaneously. Enhancement or inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. 12(R)-HETrE had no effect on the nonimmunologic inflammatory skin reaction induced by phorbol myristate acetate, suggesting selectivity toward DTH. We conclude that 12(R)-HETrE enhances DTH via a yet to be determined mechanism and that its stereoisomer, 12(S)-HETrE, may be a useful antagonist for studying the inflammatory actions of this eicosanoid. PMID- 7798641 TI - Agonist-induced expression of tissue inhibitor of metalloproteinases and metalloproteinases by human macrophages is regulated by endogenous prostaglandin E2 synthesis. AB - The regulatory effect of endogenously synthesized eicosanoid metabolites on the expression of tissue inhibitor of metalloproteinases (TIMP), interstitial collagenase, and 92-kDa gelatinase by human macrophages was examined. TIMP and metalloproteinase production were stimulated with three agonists that produce distinct patterns of eicosanoid synthesis: lipopolysaccharide (10 micrograms/ml), denatured collagen (10 micrograms/ml), or zymosan (1 mg/ml). Indomethacin (3 micrograms/ml) or MK886 (3 microM), a specific inhibitor of 5-lipoxygenase, was used to examine the role of endogenous metabolites of arachidonic acid. Regardless of the agonist used, TIMP production by macrophages was inhibited 65% by indomethacin, synthesis of interstitial collagenase was reduced 70%, and expression of 92-kDa gelatinase was decreased 40%. In contrast, inhibition of leukotriene synthesis had no effect on metalloproteinase or TIMP production. The agonist-stimulated increase in TIMP and collagenase production was directly correlated to the cumulative prostaglandin E2 level induced by the agonist used. However, if response to an agonist was poor, the exogenous addition of prostaglandin E2 could not increase TIMP or collagenase production more than twofold, indicating an important permissive effect of the agonist on the regulation of each protein's expression. The mechanism of indomethacin inhibition of TIMP and collagenase production was studied by labeling the cells with [35S] methionine and performing immunoprecipitation using specific antiserum. Indomethacin markedly inhibited the lipopolysaccharide-induced biosynthesis of both TIMP and collagenase. Northern analysis revealed parallel suppression of TIMP and collagenase steady-state mRNA levels by indomethacin, indicating pretranslational control. The regulation of inflammatory-cell TIMP and interstitial collagenase expression by prostaglandin E2 suggests that therapy inhibiting the cellular response to prostaglandins may be useful in cutaneous and systemic disease states involving macrophage-mediated connective-tissue destruction. PMID- 7798642 TI - Ultraviolet B-induced apoptosis of keratinocytes in murine skin is reduced by mild local hyperthermia. AB - Two components of sunlight, ultraviolet (UV) B (290-320 nm) and infrared (greater than 700 nm), each cause damage to the skin. However, we recently identified a protective response in which heat reduces UVB-induced killing of cultured keratinocytes. Here, this investigation is extended to the living epidermis. The effects of hyperthermic preconditioning upon UVB-induced apoptosis were studied morphologically with hematoxylin and eosin staining, and biochemically with TUNEL (terminal deoxynucleotide transferase nick-end labeling) to measure endonucleolytic cleavage of DNA in situ. Anesthetized SKH-1 hairless mice were exposed to UVB light (0 to 120 mJ/cm2), after which their skin was biopsied at 24 h and paraffin sections were stained with hematoxylin and eosin or with TUNEL. Apoptotic keratinocytes were found to increase after UVB in a dose-related manner. In contrast, if one flank of the mouse was pretreated at 40 degrees C for 1 h and both flanks subsequently were UVB-irradiated at 6 h, the resulting formation of apoptotic cells was reduced twofold or more in the heated flank. Protection appeared by 3 h, reached a maximum at 6 h, and disappeared by 12 h. In summary, heat induces a transient protective effect that reduces UVB-mediated death of keratinocytes in skin at physiologically attainable doses of heat and UVB. PMID- 7798643 TI - Repair of ultraviolet B and singlet oxygen-induced DNA damage in xeroderma pigmentosum cells. AB - Ultraviolet B (UVB) (290-320 nm) is capable of damaging the DNA molecule directly by generating predominantly pyrimidine dimers. UVA (320-400 nm) does not alter the DNA molecule directly. However, when it is absorbed by cellular photosensitizers, it can damage the DNA molecule indirectly, e.g., by mediation of singlet oxygen, generating predominantly 8-hydroxyguanine. These indirect effects have been implicated in the mutagenic, genotoxic, and carcinogenic effects of UVA. To study the processing of directly and indirectly UV-induced DNA damage in intact, DNA-repair-proficient and -deficient human cells, we used the replicating plasmid pRSVcat, either irradiated with up to 10 kJ/m2 UVB or treated with the photosensitizer methylene blue plus visible light (which generates singlet oxygen). These treated plasmids were introduced into lymphoblast lines from normal donors or from patients with xeroderma pigmentosum (XP) complementation groups A, C, D, E, and variant. DNA repair was assessed by measuring activity of reactivated chloramphenicol-acetyl-transferase enzyme, encoded by the plasmid's cat gene, in cell extracts after 3 d. As expected, the repair of UVB-induced DNA damage was reduced in all XP cell lines, and the degree varied with the complementation group. XP-A, -D, -E, and -variant cells were normally efficient in the repair of singlet oxygen-induced DNA damage. Only three of four XP-C cell lines showed a markedly reduced repair of these lesions. This indicates differential DNA-repair pathways for directly and indirectly UV-induced DNA damage in human cells and suggests that both may be affected in XP-C. PMID- 7798644 TI - Human keratinocytes express the three major splice forms of vascular endothelial growth factor. AB - Vascular endothelial growth factor is a powerful mitogen for endothelial cells, recently reported to be produced by keratinocytes. In the present work, we examined human keratinocytes in primary culture for the splice variants of vascular endothelial growth factor. In situ hybridization revealed that 100% of cultured human keratinocytes expressed mRNA for this cytokine, and analysis by reverse transcriptase-polymerase chain reaction indicated that three species of mRNA were produced. Southern hybridization and size calculations of PCR products revealed mRNA species corresponding to 121, 165, and 189 amino-acid forms of this cytokine. Using a rabbit anti-vascular endothelial growth factor antiserum, we radioimmunoprecipitated two molecular weight forms (approximately 45 and 58 kDa, non-reducing conditions) from keratinocyte culture supernatants. Under reducing conditions, three bands of approximately 15, 20, and 24 kDa appeared, corresponding with the predominant forms of vascular endothelial growth factor described. We propose that secretion of vascular endothelial growth factor by human keratinocytes in vivo sustains angiogenesis during physiologic tissue repair and in pathologic states accompanied by neovascularization. PMID- 7798645 TI - Neurofibromatosis 2 and neurilemmomatosis gene are identical. AB - Neurofibromatosis 2 (NF2) is an autosomal dominant disorder characterized by the occurrence of bilateral acoustic neuromas, as well as meningiomas and schwannomas. The gene locus for NF2 resides on chromosome 22q12 and has been cloned recently. Neurilemmomatosis is characterized by multiple cutaneous and spinal neurilemmomas without other signs of NF1 or NF2. Many cases with this disorder include the diagnosis of neurofibromatosis or other rare diseases unexplained by current nosology. In this study, we analyzed the peripheral leukocytes and tissue from cutaneous neurilemmomas of seven patients with neurilemmomatosis using DNA markers for different regions of chromosome 22. We detected allelic losses in three of seven tumors from seven patients with a probe for the NF2 region of the long arm of chromosome 22 and the germ-line mutations in two of three tumors from the same three patients. Mutations in the NF2 gene were a deletion from at least codon 334 to 579 and G insertion at codon 42. We conclude that the neurilemmomatosis locus lies within the NF2 region and that these diseases might be identical. PMID- 7798647 TI - Nle4DPhe7 alpha-melanocyte-stimulating hormone increases the eumelanin:phaeomelanin ratio in cultured human melanocytes. AB - In mammals, melanin exists in two chemically distinct forms: the red-yellow phaeomelanin and the brown-black eumelanin. Although administration of the pigmentary hormone alpha-melanocyte-stimulating hormone (alpha MSH) and its synthetic analogue Nle4DPhe7 alpha MSH induces skin darkening in man, the increases in melanogenesis in cultured human melanocytes in response to these peptides are relatively small. However, it is possible that MSH affects the eumelanin:phaeomelanin ratio rather than total cellular melanin. Thus, this study examined the specific effects of Nle4DPhe7 alpha MSH on the two melanins in cultured human melanocytes, quantifying eumelanin and phaeomelanin by high performance liquid chromatography. Nle4DPhe7 alpha MSH induced significant increases in the eumelanin content of these cells while having lesser and varied effects on the levels of phaeomelanin. As a consequence, the eumelanin:phaoemelanin ratio was increased in every culture. These results demonstrate that Nle4DPhe7 alpha MSH affects melanin type in human melanocytes and suggest a possible mechanism by which this peptide induces skin darkening in man. PMID- 7798646 TI - Changes in expression of apoptosis-associated genes in skin mark early catagen. AB - Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcriptase-polymerase chain reaction, we examined in this study the expression in total skin, throughout one hair cycle, of a series of regulatory genes associated with apoptosis. We show that gene expression within skin is hair-cycle-dependent. Transforming growth factor-beta was expressed immediately before catagen; therefore, it might be involved in the early signaling of this process. Tumor necrosis factor-beta was expressed during catagen and might be involved in follicular apoptosis. Several proto-oncogenes and transcription factors have been described in the regulation of apoptosis in other systems. Here we show that the transcript levels of c-myc, c-myb, and c-jun changed immediately before or during early catagen and thus could be involved in the signaling or regulation of catagen. Levels of p53 remained constant throughout anagen and catagen, suggesting that p53 is not involved in the developmentally induced apoptosis of the hair follicle. The variable expression throughout the hair cycle of the genes described demonstrates the dynamic changes of the skin and underscores the importance of studying the complete hair cycle when characterizing any molecule in skin. PMID- 7798648 TI - Differences between connective tissue-epithelial junctions in human skin and the anagen hair follicle. AB - Although the ultrastructure of the dermal-epidermal junction has been well characterized, little is known about the junctions between the dermal papilla and the surrounding epithelial cells of the hair bulb, or between the connective tissues and the epithelial cells on the outside of the hair follicle. Because the dermal papilla plays a major role in controlling the hair follicle, we also examined the ultrastructure of the potentially important dermal papilla epithelial junction in normal scalp anagen follicles. The dermal-epidermal junction in skin was a trilaminar basement membrane characterized by the anchoring points of hemidesmosomes and tonofilaments in keratinocytes. In the hair follicle, the junction that separated the dermal papilla and epithelial cells was a trilaminar basement membrane, but relatively few putative anchoring points were seen. These were similar to modified dermal-melanocyte junctions, in which the intercellular cytoplasmic filaments do not come together at an attachment plaque, the laminar components tend to be thinner, and the anchoring fibrils beneath the lamina densa are fewer. A trilaminar membrane also was interposed between the connective and epithelial tissues on the outside of the follicle, but nothing that resembled a hemidesmosome or any other type of anchoring structure was seen. The difference in structure of the junctional complex between skin and hair follicles probably reflects the relatively permanent state of the epidermis, compared to the dynamic processes involved during the anagen phase of the hair follicle. PMID- 7798649 TI - Protective and disease-enhancing immune responses to respiratory syncytial virus. AB - The National Institutes of Health, Centers for Disease Control and Prevention, and World Health Organization jointly sponsored a workshop on protective and disease-enhancing immune responses to respiratory syncytial virus (RSV). The primary purpose of the meeting was to discuss protective and disease-enhancing immune responses to RSV in the context of opportunities and barriers to the development of RSV vaccines. Although both live attenuated and subunit vaccines have been developed, it is not yet clear if any of these vaccines will be safe and effective. The fact that neither the disease-enhancing nor the protective immune response to RSV is well understood or well characterized is an important barrier to development of these vaccines. Studies in animal model systems and newly developed immunologic tools, however, provide hope that these barriers can be overcome and a safe and effective RSV vaccine can be developed. PMID- 7798650 TI - Comparison of different beta-lactam-glycopeptide-gentamicin combinations for an experimental endocarditis caused by a highly beta-lactam-resistant and highly glycopeptide-resistant isolate of Enterococcus faecium. AB - A synergistic bactericidal effect between penicillin, vancomycin, and gentamicin has been described against enterococci highly resistant to beta-lactams and glycopeptides. Since such a synergy was also observed in vitro between ceftriaxone, teicoplanin, and gentamicin against Enterococcus faecium 70/90, the efficacy of different combinations including penicillin or ceftriaxone, vancomycin or teicoplanin, and gentamicin was compared in vivo in experimental endocarditis. In vitro, all four triple combinations provided a bactericidal effect. In rabbits, after a 5-day treatment, the ceftriaxone-vancomycin gentamicin combination was the most effective, both in reducing the total bacterial titers and in eradicating the subpopulation resistant to the synergy. Compared with the 5-day regimen, 10- and 20-day regimens of ceftriaxone vancomycin-gentamicin, each followed by a 3-day antibiotic-free period, increased the number of sterilized animals but failed to avoid the emergence of resistant bacteria, which occurred in 10%-20% of animals. PMID- 7798651 TI - The effect of variations in the expression of pili on the interaction of Neisseria meningitidis with human nasopharyngeal epithelium. AB - Bacterial adherence is essential to colonization of the nasopharynx by Neisseria meningitidis, and pili may facilitate adherence. Scanning electron microscopy and immunogold labeling were used to study the interaction of 2 piliated and 1 nonpiliated variant of N. meningitidis with nasopharyngeal mucosa in an adenoid organ culture system with an air-mucosal interface. Meningococcal infection caused epithelial damage, loss of ciliated epithelium, and ciliary disorganization, which progressed with time and were greater with the piliated strains. Pili increased adherence of meningococci to the mucosa, and there was tropism of piliated strains for nonciliated cells containing microvilli, damaged epithelium, and sites of cell separation. Bacterial adherence was associated with a change in the appearance of the microvilli. PMID- 7798652 TI - Correlation between susceptibility of infants to infections and interaction with neutrophils of Escherichia coli strains causing neonatal and infantile septicemia. AB - The ability of Escherichia coli strains causing invasive infections to associate to human neutrophils and induce oxygen radicals was studied in three groups of blood isolates from neonates and infants: low-virulence septicemia strains (LVS), normal septicemia strains (NS), and meningitis strains (M). Infants were classified by susceptibility to infection as low- (LR) or high-risk (HR). All LVS strains were isolated from HR infants and showed higher association to neutrophils (P < .05) and induced a higher oxidative response (P < .05) compared with that of NS and M strains from LR infants. Three LVS strains caused the cells to release oxidative metabolites extracellularly. Thus, impaired interaction with neutrophils is characteristic of virulent clones of E. coli capable of causing invasive infection in healthy full-term neonates. Furthermore, increased extracellular release of oxygen metabolites could harm the surrounding tissue and potentiate the inflammatory process. PMID- 7798653 TI - Age-related differences in cell-mediated immunity to varicella-zoster virus among children and adults immunized with live attenuated varicella vaccine. AB - Live attenuated varicella vaccine elicits protection against varicella-zoster virus (VZV), but adults require two doses to achieve optimal seroconversion rates. To assess the potential role of cell-mediated immunity (CMI), T cell proliferation to VZV antigen was compared in children and adults. Mean stimulation indices (SI) in two cohorts of 39 children tested 6 weeks after vaccination were 28.6 +/- 6.21 and 22.1 +/- 3.84, whereas 20 adult vaccines had a mean SI of 9.1 +/- 0.99 (P = .04). Vaccinees had significant increases in CMI after a second dose of vaccine. At 1 year, VZV CMI was significantly lower in adults after two doses (10.0 +/- 1.13 vs. 15.6 +/- 1.77; P = .02), even though 82% of children received one dose. Limitations in the adult helper T cell response to VZV antigens may explain the need for booster doses to elicit effective immunity and the more frequent occurrence of varicella when adult vaccines are exposed to wild type virus. PMID- 7798654 TI - Effects of endotoxin in the lungs of neonatal rats: age-dependent impairment of the inflammatory response. AB - Age-dependent maturation of the intrapulmonary inflammatory responses to bacterial lipopolysaccharide (LPS) was studied because nosocomial gram-negative infections cause morbidity in newborn infants. Escherichia coli LPS or live E. coli were injected into the airways of neonatal or adult rats; intrapulmonary recruitment of leukocytes was measured 6 h later. Neonates showed age- and dose dependent impairment of intrapulmonary neutrophil recruitment after intratracheal administration of LPS or live E. coli that persisted for the first 28 days of life. Neonatal and adult alveolar macrophages released similar amounts of neutrophil chemotactic activity and tumor necrosis factor in response to incubation with LPS in vitro. Treatment of neonates with intratracheal or systemic interferon-gamma did not augment the response to LPS. Thus, intrapulmonary inflammatory responses to LPS and gram-negative bacteria are impaired early in life and do not approach adult levels until approximately 4 weeks of age. PMID- 7798655 TI - Protective effects of a recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in an animal model of gram-negative sepsis. AB - Bactericidal/permeability-increasing protein (BPI) has bactericidal properties and also binds lipopolysaccharide (LPS). The ability of a recombinant amino terminal fragment of BPI to protect mice from death after challenge with a number of different strains of Escherichia coli was tested. BPI prevented death in animals challenged with the J5 rough strain but not with smooth strains O111:B4 and O7K1. Protection was associated with a reduction in serum LPS and tumor necrosis factor-alpha levels but not with reduction in blood bacterial counts. BPI was effective at protecting against death in mice injected with purified O111:B4 LPS. Lack of protection after injection with live O111:B4 and O7K1 may be due to production by these models of approximately 1000-fold higher blood bacterial count compared with J5. Thus, BPI is a promising therapy in the treatment of gram-negative septic shock, although the range of organisms against which it is effective remains to be determined. PMID- 7798656 TI - Effect of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor in animal models of infection. AB - Intracisternal or intraarticular inoculation of rabbit recombinant interleukin (IL)-1 beta and rabbit tumor necrosis factor-alpha combined with IL-1 receptor antagonist (IL-1RA) and soluble tumor necrosis factor receptor (sTNFR), respectively, produced significantly less inflammation in rabbits than after inoculation of these cytokines alone. In contrast, when Haemophilus influenzae type b (Hib) or Hib lipooligosaccharide (LOS) was given intraarticularly with IL 1RA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimental meningitis model, IL-1RA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Hib LOS. These data indicate that specific cytokine inhibitors (sTNFR and IL-1RA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteria or their products and suggest caution in using them to treat these infectious conditions in humans. PMID- 7798657 TI - Temporal trends and transmission patterns during the emergence of multidrug resistant tuberculosis in New York City: a molecular epidemiologic assessment. AB - To ascertain the role of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis transmission on multidrug-resistant (MDR) tuberculosis (TB) emergence in New York City, medical records, drug susceptibilities, and restriction fragment length polymorphisms (RFLPs) of TB cases at a city hospital between two 9-month periods (1987-1988 and 1990-1991) were reviewed. The proportion of TB patients with MDRTB increased from 10% (27/267) to 17% (38/222; P = .03). Among MDRTB patients of known HIV status, the proportion with HIV increased from 16% (3/19) to 58% (22/38; P = .006). HIV-infected MDRTB patients were more likely than the seronegative ones to have initial MDRTB (88% vs. 56%; P = .03). Among 56 MDR cases with RFLP results, 12 had unique patterns; 44 belonged to one of six clusters. During 1990-1991, 27 (75%) of 36 MDRTB patients were infected with strains isolated from HIV-seronegative patients during 1987-1988. The increase in MDRTB caused by transmission from immunocompetent to immunocompromised persons underscores the urgency of TB control in populations with increasing HIV prevalence. PMID- 7798658 TI - Quantitation of human cytomegalovirus DNA from peripheral blood cells of human immunodeficiency virus-infected patients could predict cytomegalovirus retinitis. AB - Human cytomegalovirus (CMV) DNA copy number in white blood cells from both human immunodeficiency virus (HIV)-seronegative and HIV-seropositive patients was amplified from the immediate-early region of CMV DNA and quantified by colorimetric detection of the hybridization of the amplification product to a detector oligonucleotide probe in microtiter wells. By Mann-Whitney U test, significantly higher (P < .05, two-tailed) copy numbers of CMV DNA were detected in HIV-seropositive patients with retinitis than in either patients with < 100 CD4 cells/mm3 and no symptomatic CMV disease or HIV-seropositive patients with > 100 CD4 cells/mm3. By prospective monitoring for increases in CMV DNA copy number, it may be possible to identify HIV-seropositive patients who are at imminent risk for development of symptomatic CMV retinitis. PMID- 7798659 TI - Formulation of an immunogenic human cytomegalovirus vaccine: responses in mice. AB - The immunogenicity of a vaccine formulation consisting of recombinant-derived human cytomegalovirus (HCMV) glycoprotein B (UL55) combined with a chemically defined adjuvant derived from saponin, QS-21, was evaluated in mice. The immune responses of mice given the gB/QS-21 formulation were compared with those induced by gB combined with either Freund's adjuvant or aluminum hydroxide. The gB/QS-21 combination induced higher levels of virus-binding antibodies and significantly higher levels of virus-neutralizing antibodies than gB combined with either Freund's adjuvant or aluminum hydroxide. Animals given gB/QS-21 exhibited IgG subclass switching and produced significant titers of virus-specific IgG2a antibodies. Furthermore, animals given gB/QS-21 produced antigen-specific cytotoxic spleen cells. Because of its immunogenicity, a subunit vaccine containing HCMV gB and QS-21 offers a potential approach to the immunoprophylaxis of HCMV disease. PMID- 7798660 TI - Virus-specific antibody responses to human cytomegalovirus (HCMV) in human immunodeficiency virus type 1-infected persons with HCMV retinitis. AB - Human cytomegalovirus (HCMV) causes retinitis and is the leading cause of blindness in patients infected with the human immunodeficiency virus (HIV). While most patients with HIV are HCMV seropositive, not all will develop clinical complications from it. The immune responses that can prevent the development of HCMV retinitis are unknown. The levels of anti-HCMV antibodies, including responses to the two major envelope proteins, gpUL55 (gB) and gpUL75 (gH), which are the targets of neutralizing antibody (NA), were examined in HIV-infected patients with and without retinitis. No specific deficiency in the antibody response of retinitis patients was observed. However, higher levels of NA were associated with a more favorable clinical course. These results indicate that antibodies may modulate progression of disease, and they suggest a possible role for the exogenous administration of NA in patients who develop HCMV retinitis. PMID- 7798661 TI - Enhancement of NK cell-mediated antibody-dependent lysis of recombinant gp120 coated CD4 cells by complement. AB - The contribution of complement to NK cell lysis of CD4 cells expressing recombinant gp120 (rgp120) was investigated. Peripheral blood mononuclear cells were used as effector cells in a Cr release assay against purified CD4 target cells that had been coated with rgp120. Assays included human immunodeficiency virus (HIV) antibodies and a complement source alone and in combination to determine their importance in mediating cytotoxicity. NK cells were confirmed to be the effector cells in the lysis of rgp120-coated CD4 targets. Anti-HIV was crucial for lysis and cytotoxicity was enhanced by C3 deposition on targets. However, a prozone effect was observed, with reduced IgG binding, C3 deposition, and NK cell lysis at serum concentrations > 10 micrograms IgG/mL. The susceptibility of these CD4-gp120-antibody-C3 complexes to NK cell lysis may contribute to progressive depletion of CD4 cells in HIV infection. PMID- 7798662 TI - Infection of oral mucosal cells by human immunodeficiency virus type 1 in seropositive persons. AB - Molecular studies have revealed significant amounts of human immunodeficiency virus type 1 (HIV-1) provirus DNA in saliva of HIV-infected persons. However, cellular localization has not been determined. In situ polymerase chain reaction (IS-PCR) was done on saliva-associated cells for localization of HIV-1 provirus DNA. Results indicate its presence in the nuclei of saliva-associated epithelial cells in 29 (83%) of 35 HIV-1-seropositive subjects. In 24 (83%) of the 29 IS-PCR positive samples, 0.1%-4.0% of the mucosal epithelial cells exhibited nuclear localization of HIV-1 DNA. In addition, HIV-1 provirus DNA was detected in monocytes or lymphocytes of all salivary samples from the 35 subjects. The localization of HIV-1 provirus DNA indicates that epithelial cells are another cell type infected by HIV-1 in vivo. These findings suggest epithelial cells in other body sites might also be infected with HIV-1. PMID- 7798663 TI - Detection of hepatitis B virus precore TAG mutant by an amplification-created restriction site method. AB - A new method for detecting the hepatitis B virus (HBV) precore 1896 G-->A mutation is described. This mutation prevents hepatitis B e antigen production by introducing a TAG stop codon and has been associated with severe chronic and fulminant hepatitis. The method is based on a polymerase chain reaction (PCR) that creates a restriction enzyme (Bsu36I) cleavage site if the mutation is present. After incubation of the PCR product with Bsu36I and a subsequent agarose gel electrophoresis, the presence of the TAG mutant is revealed by an altered position of the DNA band. The method was compared with direct sequencing on 36 serum samples and correctly identified all samples containing mutant HBV. The TAG mutant was present in 17 cases (as mixed wild type and mutant virus in 4). Twelve of 18 patients with advanced liver disease confirmed by biopsy carried mutant HBV. This method of detecting HBV precore 1896 G-->A should be useful for evaluation and follow-up of patients and for prevalence studies. PMID- 7798664 TI - Parenteral influenza vaccination induces a rapid systemic and local immune response. AB - The kinetics of the local immune response in the upper respiratory tract to parenterally administered inactivated split trivalent influenza vaccine were examined in 19 healthy subjects. Influenza virus-specific antibody-secreting cells (ASC) could be detected as early as 2 days after vaccination in peripheral blood and tonsils, with a peak at approximately 1 week after vaccination and a decline to insignificant levels after 6 weeks. Circulating ASC produced IgG, IgA, and IgM, whereas ASC in tonsils produced mainly IgA and IgM. Influenza virus specific antibodies were predominantly IgG and IgM in serum and IgA in oral fluid; they rose after 1 week and were elevated at 6 weeks. This may indicate a secretory involvement of the anti-influenza virus response in the upper respiratory tract. Parenteral influenza vaccination induced an immediate and significant immune response in both the upper respiratory tract and peripheral blood. PMID- 7798665 TI - Brazilian purpuric fever caused by Haemophilus influenzae biogroup aegyptius strains lacking the 3031 plasmid. AB - Brazilian purpuric fever (BPF) is a life-threatening pediatric infection caused by Haemophilus influenzae biogroup aegyptius (Hae), an organism formerly associated with only self-limited purulent conjunctivitis. Strains of Hae causing BPF have a 24-MDa plasmid with a specific AccI restriction pattern designated 3031. This plasmid was thought to code for a virulence factor because it had been detected only among Hae strains isolated from BPF cases or their contacts. From 3 typical BPF cases recently identified in Sao Paulo State, sterile-site Hae isolates were obtained; these isolates were similar to earlier BPF-associated Hae except they did not possess a 3031 plasmid. HindIII restricted chromosomal DNA from these strains was probed with purified 3031 plasmid DNA under high stringency conditions. There was no evidence that 3031 plasmid DNA had become chromosomally integrated. It appears that the 3031 plasmid does not code for BPF specific virulence factors. PMID- 7798666 TI - Flagellar serotypes of Salmonella typhi in Indonesia: relationships among motility, invasiveness, and clinical illness. AB - While the H1-d flagellar serotype of Salmonella typhi has been found worldwide, the H1-j serotype occurs only in Indonesia. A cross-sectional survey in Indonesia compared epidemiologic, clinical, and pathogenetic characteristics of these two serotypes. S. typhi isolates were collected from patients with acute typhoid fever in four Indonesian cities. Flagellar serotype was determined by polymerase chain reaction amplification of the fliC locus of the flg gene. Of 321 isolates, 51 (15.9%) were H1-j. Patients with H1-j infection were older than those with H1 d (P < .001). Among 30 patients with known clinical outcomes, H1-j infection was associated with milder clinical illness than H1-d (P = .06). In vitro, H1-j isolates were both less motile on semi-solid agar plates (P = .004) and less invasive of HEp-2 cells (P = .002) than H1-d isolates. The association of decreased severity of illness with decreased motility and invasiveness suggests that flagellar properties are a component of S. typhi's virulence. PMID- 7798667 TI - Nasal carriage of Staphylococcus aureus as a major risk factor for wound infections after cardiac surgery. AB - To evaluate the importance of nasal carriage of Staphylococcus aureus as a risk factor for the development of wound infection at the sternotomy site after cardiac surgery, a case-control study was done. The study population consisted of 1980 consecutive patients. Cases were all patients who developed a sternal wound infection from which S. aureus was cultured. Forty cases were identified, and 120 controls were selected. Preoperative nasal carriage of S. aureus, insulin dependent diabetes mellitus, and younger age were identified as significant risk factors. The crude odds ratio of nasal carriage was 9.6 (95% confidence interval, 3.9-23.7). The median postoperative length of hospital stay for cases was 30 days longer than for controls. Mortality was also significantly higher for cases than for controls (10.0% and 0.8%, respectively). PMID- 7798668 TI - Potentiation of Staphylococcus epidermidis catheter-related bacteremia by lipid infusions. AB - Lipid infusions given to low-birth-weight neonates are associated with coagulase negative staphylococcal bacteremia. A rabbit model of catheter-related Staphylococcus epidermidis bacteremia was used to compare infection rates between animals receiving 20% lipid infusions with those receiving 10% glucose infusions. Bacterial growth was detected in 43 (66%) of 65 blood cultures obtained during lipid infusions but only 6 (7%) of 91 blood cultures obtained during glucose infusions (P < .001). S. epidermidis was cultured from 7 of 9 catheters recovered from lipid-infused rabbits but from only 3 of 13 catheters from glucose-infused rabbits (P = .016). Lipid but not glucose solutions containing low levels of protein (0.1%-1.0%) supported the survival and growth of S. epidermidis. These results suggest that lipids contribute to the survival and growth of S. epidermidis on contaminated catheters, enhancing the potential of these organisms to disseminate and cause bacteremia. PMID- 7798670 TI - High levels of interleukin-10 during the initial phase of fulminant meningococcal septic shock. AB - Interleukin (IL)-10 has an important antiinflammatory effect by inhibiting endotoxin-induced production of proinflammatory cytokines, such as tumor necrosis factor-alpha and IL-1. Since both cytokines are produced in massive amounts during fulminant meningococcal septic shock and are associated with severity of disease, IL-10 was measured in plasma samples of 25 consecutive children with fulminant meningococcal septic shock shortly after admittance to a pediatric intensive care unit. High levels of IL-10 (median, 6021 pg/mL; range, 137-24,600) were found in surviving patients (median, 1268 pg/mL; range, 137-24,600) and in those who died (median, 9915 pg/mL; range, 3996-14,100). IL-10 levels correlated weakly (r = .38; P = .055) with severity of disease as measured by the Glasgow meningococcal septicemia prognostic score. The findings indicate that IL-10 is produced in massive amounts in the initial phase of fulminant meningococcal septic shock. PMID- 7798669 TI - Increase in interleukin-6 serum level preceding fever in granulocytopenia and correlation with death from sepsis. AB - Serum interleukin (IL)-6 levels measured by ELISA were correlated with the clinical course of 53 adults with hematologic malignancies in 95 episodes of chemotherapy-induced leukocytopenia (< 1000/microL). The median IL-6 level was 15 pg/mL (range, < 3-123) in 27 episodes without fever. This level was 14.5 pg/mL (range, < 3-187) 72-48 h before onset of fever, 78 pg/mL (range, < 3-170) 24 h before fever in episodes with unexplained fever (FUO), and 182 pg/mL (range, 63 1076) 24 h before fever in episodes with positive blood cultures (P < .001). Within 24 h after onset of fever, median IL-6 level was 171 pg/mL (range, 53 1134) in episodes of FUO, 444 pg/mL (range, 38-7973) in episodes with gram negative bacteremia, and 2017 pg/mL (range, 76-7253) with gram-positive bacteremia (P < .01). IL-6 levels increased before death in all 13 patients who died of sepsis. Median level was 7253 pg/mL (range, 445-95,906) within 3 days of death. Determination of IL-6 may be useful for early assessment and as a prognostic tool in leukocytopenic fever. PMID- 7798671 TI - Increased plasma levels of human interleukin for DA1.a cells/leukemia inhibitory factor in sepsis correlate with shock and poor prognosis. AB - Animal study results have suggested a role in sepsis for human interleukin for DA1.a cells/leukemia inhibitory factor (HILDA/LIF). HILDA/LIF and interleukin-6 (IL-6) levels were prospectively studied by serial ELISAs in 34 septic patients. HILDA/LIF was detected in 11 of 34 patients at plasma levels of 100-37,000 pg/mL. Peak HILDA/LIF levels correlated with increased temperature and creatinine and IL 6 and with decreased arterial CO2 (P < .05). Multivariate analysis showed that shock and decreased arterial CO2 accounted for 75% of peak HILDA/LIF plasma variations (R2 = .753). Fatal outcome was most often associated with detectable HILDA/LIF (> 56 pg/mL) and peak IL-6 plasma levels > 850 pg/mL (sensitivity, 83%; specificity, 87%), but both (at respective levels of > 480 and > 850 pg/mL) were associated with fatal outcome. HILDA/LIF was detected in septic patients exhibiting shock, and its levels correlated with higher mortality and shorter survival. PMID- 7798672 TI - Catalase expression, katG, and MIC of isoniazid for Mycobacterium tuberculosis isolates from Sao Paulo, Brazil. AB - The MIC of isoniazid, peroxidase-catalase expression, and the presence of the katG gene for 102 Mycobacterium tuberculosis isolates from patients in Sao Paulo were compared. Fifty-three isoniazid-resistant and 49 isoniazid-sensitive isolates were analyzed by polymerase chain reaction (PCR) for the presence of katG sequences. All isoniazid-sensitive and 43 (81%) isoniazid-resistant isolates expressed catalase (P = .001). None of isoniazid-sensitive and 4 (7%) of 53 isoniazid-resistant isolates lacked katG sequences. Among 6 isolates with MICs > 50 micrograms/mL, 5 (83%) did not express catalase and 2 lacked katG sequences; only 1 had complete gene deletion shown by Southern blot analysis. These findings indicate a correlation between loss of catalase and isoniazid resistance among highly resistant isolates, but these isolates were a small proportion of resistant clinical M. tuberculosis isolates from Sao Paulo. PMID- 7798674 TI - Disseminated microsporidiosis due to Septata intestinalis in patients with AIDS: clinical features and response to albendazole therapy. AB - Five patients with AIDS had disseminated infection due to Septata intestinalis, a recently described organism. S. intestinalis infection was suspected after detection of spores in stools and urine and confirmed by transmission electron microscopy of duodenal biopsies or of cell culture of urine sediment. Clinical features included chronic diarrhea that was usually associated with fever, cholangitis, sinusitis, bronchitis, or mild bilateral conjunctivitis. Mean CD4 cell count was 22/microL. Patients treated with albendazole (400 mg orally twice a day) for a mean of 19 days had a dramatic and rapid clinical response to therapy. Significant reduction of parasite shedding was also observed during therapy; S. intestinalis was cleared from stools of all patients and from urine of 3. In 2 patients, however, microsporidian spores were detected in feces during follow-up and mild diarrhea recurred. Therefore, albendazole seems to have a significant but transient effect in treatment of S. intestinalis infection. PMID- 7798673 TI - Rapid identification of a point mutation of the Mycobacterium tuberculosis catalase-peroxidase (katG) gene associated with isoniazid resistance. AB - The complete catalase-peroxidase (katG) gene DNA sequence was determined for 15 strains of Mycobacterium tuberculosis with a wide range of susceptibility to isoniazid. Five of 9 strains with isoniazid MICs > or = 1.0 microgram/mL had one or more missense mutations and all 5 strains had a common G-->T transversion in codon 463, causing the replacement of arginine with leucine and the loss of an NciI or MspI restriction site. None of 6 strains with an isoniazid MIC < 1.0 microgram/mL had mutations affecting codon 463. Restriction analysis of 43 strains with isoniazid MICs > or = 1.0 microgram/mL showed that 19 (44.2%) had lost the NciI-MspI restriction site at the locus of codon 463 while only 1 of 32 strains with isoniazid MICs < or = 1.0 microgram/L had this restriction polymorphism. These results indicate that the mutation arginine-->leucine in codon 463 of the catalase-peroxidase gene occurs in a significant fraction (44.2%) of M. tuberculosis strains with isoniazid MICs > or = 1.0 microgram/mL. PMID- 7798675 TI - Gamma delta T cells and acute primary Toxoplasma gondii infection in mice. AB - A murine model of Toxoplasma gondii infection was used to investigate whether gamma delta T cells are required to resist primary acute toxoplasmosis. The surface phenotype of peritoneal exudate and spleen cells obtained from T. gondii infected mice was examined using anti-gamma delta T cell-specific reagents and flow cytometry. Survival of mice depleted of gamma delta T cells was also followed during the acute phase of toxoplasmosis. Numbers of gamma delta T cells did not increase in spleen or peritoneal exudates of mice infected with T. gondii. Moreover, infected mice depleted of gamma delta T cells survived as long as untreated infected mice. These results indicate that gamma delta T cells do not play an important role in host defense against T. gondii infection in mice. PMID- 7798677 TI - Increased human papillomavirus infection with the increasing number of pregnancies in Indian women. PMID- 7798676 TI - Mefloquine prophylaxis in pregnancy. PMID- 7798678 TI - Serum IgA antibody response to Cryptosporidium parvum is mainly represented by IgA1. PMID- 7798679 TI - Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age. AB - To determine if immunity to human cytomegalovirus (HCMV) protects women from acquiring HCMV from their children, a blinded, randomized protocol was used to monitor seronegative women who received placebo or Towne vaccine (approximately 500 pfu) and seropositive women. Each group was similar for mean maternal (33 years) and child age (18 months) and duration of viral shedding by the child (15 months). Among 19 placebo recipients, 9 developed primary infection; 8 of 19 vaccines but only 3 of 42 naturally seropositive subjects had evidence of acquiring HCMV from their child. Wild type infection and Towne vaccine induced similar mean lymphoproliferative responses to HCMV antigens, but one dose of Towne vaccine produced mean neutralizing titers 10- to 20-fold lower than those after wild type infection. Thus, a vaccine that induces immune responses equal to those induced by wild type virus may protect healthy women from acquiring HCMV from their children. PMID- 7798680 TI - Cervical but not urinary excretion of cytomegalovirus is related to sexual activity and contraceptive practices in sexually active women. AB - The relationship between sexual activity and genitourinary excretion of cytomegalovirus (CMV) was evaluated in 1481 women at a sexually transmitted disease (STD) clinic. Among 951 who were CMV-seropositive, 16.6% had CMV isolated, from cervix alone in 9.4%, urine alone in 3.8%, and both sites in 4.2%. Isolation rates were highest in young women (P < .001). Compared with those with only cervical infection, women shedding from both cervix and urine were younger, began sexual activity when younger, had more recent partners, and a higher frequency of CMV-specific IgM, suggesting recent CMV infection. By logistic regression, cervical CMV excretion was associated with concomitant gonococcal infection (P = .008) and was less frequent in those using barrier contraception (P = .036). Isolated urinary excretion of CMV was not associated with sexual activity, concomitant cervical infections, or use of contraception. Cervical CMV infection is related to sexual activity, acquisition of other STDs, or exogenous reinfection, and urinary CMV is not. PMID- 7798681 TI - Cytomegalovirus infection is associated with absence of alveolar epithelial cell HLA class II antigen expression. AB - Cytomegalovirus (CMV) pneumonia is associated with the development of secondary immunosuppression with resultant bacterial and fungal superinfections. Because class II HLA expression within the lung may be important in normal pulmonary cell mediated immunity, the association of CMV infection of alveolar epithelial cells (AEC) with an absence of HLA class II antigens was tested. Using dual-labeling immunohistochemistry to detect CMV, AEC, endothelial cells, macrophages, and HLA class II antigens, lung tissue from patients whom died with CMV pneumonia was examined. Seventy-five percent of infected cells were AEC. In contrast to adjacent noninfected AEC, which expressed HLA-DR antigens, 91% of infected AEC were negative. There was no difference in this expression pattern between patients with or without AIDS. The absence of HLA class II antigens on infected AEC may account, in part, for the secondary immunosuppression associated with CMV pneumonia. PMID- 7798682 TI - The molecular epidemiology of human immunodeficiency virus type 1 in Edinburgh. AB - Human immunodeficiency virus (HIV) type 1 sequences obtained from HIV-infected persons in different risk groups in Edinburgh were studied to determine the number and origin of virus variants and patterns of virus transmission. Phylogenetic analysis revealed that 12 of 14 hemophiliac patients who had been exposed to a single common batch of factor VIII had closely related gag gene sequences. Sequences from intravenous drug users and patients infected through heterosexual contact formed another distinct group, and 2 other hemophiliacs formed a third group. However, epidemiologic relationships inferred from analysis of the V3 region of the env gene were less conclusive, especially when the V3 loop was taken in isolation. This appears to be due to the length of time since infection and the action of selection, which has favored the independent appearance of similar V3 loop variants. PMID- 7798683 TI - Long-term efficacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United States-People's Republic of China Study Group on Hepatitis B. AB - Perinatal transmission of hepatitis B virus (HBV) contributes to the high prevalence of chronic infection in China and many other countries. In a placebo controlled trial among 166 infants, the 12-month efficacy of active postexposure prophylaxis to prevent chronic perinatal HBV infection varied by vaccine (range, 45%-89%). In a 5-year follow-up study, 2 additional infants became chronically infected with HBV, and the efficacy of active prophylaxis was estimated to be 38% and 72% for the two vaccines at 5 years. In addition, 80% of immunized infants continued to have protective levels of antibody at the end of 5 years. However, among 27 infants who received passive-active immunoprophylaxis with high-dose hepatitis B immune globulin, only 60% (11/19) had protective antibody levels. These data indicate that active postexposure immunization initiated soon after birth continues to provide protection during early childhood when there is a high risk of chronic HBV infection. PMID- 7798685 TI - Summary of the 29th United States-Japan joint Conference on Cholera and Related Diarrheal Diseases. PMID- 7798684 TI - Selective depletion of V beta-bearing T cells in patients with severe invasive group A streptococcal infections and streptococcal toxic shock syndrome. Ontario Streptococcal Study Project. AB - The V beta repertoire of T cells of patients with gram-positive group A streptococcal (GAS) and non-GAS infections was analyzed to seek evidence for the role of superantigens in streptococcal toxic shock syndrome. No evidence of V beta overexpression but a consistent pattern of depletion of V beta 1, V beta 5.1, and V beta 12 was observed in patients with severe GAS infections. This pattern of V beta depletion was not observed in patients with nonsevere GAS infections or with severe non-GAS gram-positive infections. T cells from patients with severe GAS infections showed evidence of apoptosis; no apoptosis was found when there was no evidence of V beta depletion. There was no correlation with streptococcal M or T serotype or known spe genes. The depletion of specific V beta-bearing T cells in patients with severe GAS infections supports the role of a superantigen in these infections. The in vivo pattern of V beta specificity implicates a novel superantigen(s) in this disease. PMID- 7798686 TI - A role for fibrinogen in the streptokinase-dependent acquisition of plasmin(ogen) by group A streptococci. AB - Acquisition of plasmin(ogen) by group A streptococci occurs by two distinct pathways. In addition to the well-characterized direct interaction of plasmin with cell-surface receptors on group A streptococci, a second pathway dependent on streptokinase and a nonplasminogen factor(s) present in human plasma was identified. The role of streptokinase in the second pathway was not merely as a plasminogen activator, since substitution of the plasminogen activator urokinase did not result in the capture of plasmin(ogen) by bacteria in the presence of plasminogen-depleted plasma. However, if streptokinase was added to plasmin that had been generated by treatment of plasminogen with urokinase, the ability of the bacteria to capture plasmin in the presence of plasminogen-depleted plasma was restored. Fibrinogen present in human plasma was identified as the major factor required for streptokinase-dependent uptake of plasmin(ogen) by group A streptococci. PMID- 7798687 TI - The impact of conjugate vaccine on carriage of Haemophilus influenzae type b. AB - Conjugate vaccines against Haemophilus influenzae type b (Hib) may modify Hib pharyngeal colonization. Hib colonization was compared in 371 infants and their families. In Oxfordshire, infants received PRP-T (polyribosylribitol phosphate conjugated to tetanus toxoid) and in Buckinghamshire they did not (controls). Infants were followed at 6, 9, and 12 months of age. Also, 6 unvaccinated Hib carriers were vaccinated and followed for 6 weeks. Hib acquisition was lower in vaccinees than controls (P < .01). During surveillance, 1.5% of vaccinees and 6.3% of controls carried Hib (P = .04). Among those with family Hib exposure, the carriage rates were 8.7% and 38.5% (P = .07), respectively. Hiv carriage rates were lower among vaccinees' unvaccinated siblings. Giving conjugate vaccine to a child carrying Hib did not rapidly terminate carriage. Thus, a primary means by which herd immunity to Hib is induced in a vaccinated population may be through reduction or delay in the initial acquisition of Hib. PMID- 7798688 TI - Transplacental antibody transfer following maternal immunization with polysaccharide and conjugate Haemophilus influenzae type b vaccines. AB - Passive transfer of antibody to infants born to women immunized during the third trimester of pregnancy with a Haemophilus influenzae type b (Hib) vaccine (PRP polysaccharide or Hib conjugates PRP-D or HbOC) was studied in 50 mothers and infants and 47 nonimmunized mother-infant pairs. Geometric mean total PRP antibody by RIA was 1.2 micrograms/mL at delivery in unimmunized women and 21, 149, and 171 micrograms/mL in women who received PRP, PRP-D, and HbOC, respectively. Mean cord PRP antibody levels were 0.29, 3.0, 17.5, and 29.3 micrograms/mL for the corresponding groups. Postimmunization and cord PRP antibody levels were higher after maternal immunization with conjugate vaccines than with PRP vaccine (P < .01). PRP IgG1 subclass was transmitted more efficiently than IgG2 (56% vs. 35%, P < .01). The proportion of anti-PRP IgG transmitted from immunized mothers to infants correlated with time between immunization and delivery. Administration of PRP conjugate vaccines to women during pregnancy resulted in higher levels of PRP antibodies in infants than did polysaccharide or no vaccine. PMID- 7798689 TI - The radial forearm flap in orofacial reconstruction. AB - This review on the radial forearm flap deals with the multiple applications possible in orofacial reconstruction using this graft. The variations are illustrated and some salient points of the method are discussed. PMID- 7798690 TI - Repair of the radial forearm flap donor site with a full-thickness graft. AB - A method of closing the radial forearm free flap donor site defect with a defatted, full-thickness skin graft is described. Its advantages of improved patient mobilization, protection of tendons, and cosmesis are discussed with reference to 16 consecutive patients treated over a period of 1 year. PMID- 7798691 TI - Mandibular reconstruction with the free fibula osteocutaneous flap. AB - Experience with 17 mandibular reconstructions by the free fibula flap is presented. The main advantages of this reconstruction method include the bicortical structure of the bone and its adaptability to conform to the mandibular contour. The only real disadvantage is the limited height of the bone graft, which does not allow alveolar ridge reconstruction. An implant-borne dental prosthesis can, however, generally be made for functional occlusal rehabilitation. PMID- 7798692 TI - The bilobed myocutaneous pectoralis major flap in closure of combined intra- and extraoral defects. AB - Oral carcinomas may eventually invade the perioral soft tissues. In such cases, tumor resection creates through and through defects. Similar defects are seen in patients with gunshot wounds. The versatility of the bilobed myocutaneous pectoralis major flap in closure of these defects is emphasized. The results in nine patients treated by this method are discussed. PMID- 7798693 TI - Reconstruction of the severely resorbed (Class VI) maxilla. A two-step procedure. AB - The medium-term results of 12 patients that underwent reconstruction of the severely resorbed maxilla are reported. The method described entails a two-step procedure including Le Fort I osteotomy and grafting of the floor of the sinus and nose with particulate bone and hydroxyapatite (HA). The implants were placed in a second procedure. A 5% failure rate was noted in those patients that were grafted with particulate bone mixed with HA. PMID- 7798694 TI - Localized alveolar ridge augmentation before orthodontic treatment. A case report. AB - Extraction spaces are usually characterized by narrow, atrophic alveolar ridges, which make it difficult to move teeth orthodontically within these areas. Guided tissue regeneration is often used for alveolar ridge augmentation in implantology. In the case presented, localized alveolar ridge augmentation was performed as a preliminary procedure before orthodontic closure of an edentulous space. Guided tissue regeneration enhances the possibilities of orthodontic treatment in adult patients. PMID- 7798695 TI - The Dautrey procedure in recurrent dislocation: a review of 12 cases. AB - The Dautrey procedure was used to treat 12 patients with chronic recurrent dislocation of the temporomandibular joint. There was no recurrent dislocation in 11 patients during a follow-up period of up to 5 years and 2 months, and joint function appeared to be undisturbed. The surgical procedure and evaluation of the results are presented. PMID- 7798696 TI - The pathogenesis of hypertrophic/keloid scarring. AB - The formation of hypertrophic and keloid scars after cutaneous wounding is of particular relevance to the practice of maxillofacial surgery. This paper reviews current knowledge of the local and systemic factors underlying the formation of these scars and outlines the current and potential treatment modalities for these lesions. PMID- 7798697 TI - Restoration of mandibular nonunion bone defects. An experimental study in rats using an osteopromotive membrane method. AB - Standardized through-and-through critical size defects were created in rat mandibles. After 12 weeks, the sites revealed a massive ingrowth of soft connective tissue, forming a transosseous core filling the defects. Upon reentry, the soft tissue inside the remaining bone defects was removed. On one side of the jaw, the defect was covered both buccally and lingually with an expanded polytetrafluoroethylene (e-PTFE) membrane, but on the other side no membrane was placed. Histologic analysis after 6 weeks revealed an essentially complete healing with bone of the membrane-covered defects. No cartilage was present in any of the specimens. At the control sites (no membrane), the amount of newly produced bone showed variations, most through defects revealing the presence of a remaining central portion of connective tissue. This investigation thus showed that predictable and successful bone regeneration can be achieved by the osteopromotive membrane method in treatment of nonunion defects filled with mature connective tissue. PMID- 7798698 TI - Cephalometric studies on the upper airway space in normal Chinese. AB - A detailed cephalometric analysis of the soft and hard tissues of the upper airway was conducted with lateral cephalographs from 116 normal Chinese, aged between 18 and 25 years. Normal values and deviation range were preliminarily established for the size of the tongue, soft palate, nasopharynx, oropharynx, and hypopharynx, and for the relative position of the hyoid bone and vallecula in both sexes. Statistical findings showed that there were significant differences between the sexes. Significant relationships (P < 0.001) were observed 1) between the hypopharyngeal depth and the position of the hyoid bone and the vallecula, in which the horizontal position of vallecula appears to be the best predictor of the hypopharyngeal depth, as confirmed by the multiple regression equation; 2) between the upper airway depths at four different levels; and 3) between the naso oropharyngeal area and tongue, soft palate, and oral area. The present data can be used to investigate further the upper airway in abnormal states. PMID- 7798699 TI - [Transcranial Doppler measurement of middle cerebral artery blood flow during continuous retrograde cerebral perfusion]. AB - This is the first report of cerebral blood flow measurement with transcranial Doppler (TCD) during aortic arch reconstruction using continuous retrograde cerebral perfusion (CRCP) with deep hypothermia. Cerebral blood flow velocity was measured in 6 patients. CRCP was performed via the superior vena cava (SVC) at 30 cmH2O of internal juglar vein pressure and at 18 degrees C or lower of minimum bladder temperature. During the operation, the flow velocity of the middle cerebral artery (MCA) was continuously measured with TCD fixed on the temple. The cerebral blood flow during CRCP was different in each of the 6 patient. The retrograde MCA flow could be measured during CRCP in 3 patients, and the flow velocity was 11-60% of the MCA flow velocity before cardiopulmonary bypass. In the other 3 patients, retrograde MCA flow could not be detected during CRCP, but antegrade MCA flow could be found after antegrade perfusion was resumed. The antegrade flow velocity right after CRCP became more than the MCA flow before CRCP, which was regarded as a reaction due to cerebral ischemia. All the patients awoke within several (2-9) hours after operations and had no permanent neurological complications. But 2 patients developed drowsiness for several days after the operations; their CRCP times were 127 and 131 minutes. It is concluded that CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is different in each patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798700 TI - [Clinical results of selective cerebral perfusion during reconstruction of the transverse aortic arch]. AB - Selective cerebral perfusion (SPC) has become a reliable method for brain protection during reconstruction of the transverse aortic arch. However, arterial cannulation technique for the branches of the aortic arch varies among groups, and the necessity of perfusion for the left subclavian artery is controversial. To avoid atheroembolism to the brain and malperfusion of the vertebral arterial system, we carefully selected the arterial cannulation technique according to the result of preoperative ultrasonographic and angiographic evaluation of the branches of the aortic arch, and decided the necessity of perfusion for the left subclavian artery according to the dominance of the two vertebral arteries and the result of pressure monitoring of all three branches. In this report, we analyzed our clinical results of selective cerebral perfusion on 22 consecutive patients, which was performed between April 1992 and December 1993. There were 14 atherosclerotic aneurysms and 8 aortic dissections. The flow rate for SCP was controlled by a single blood pump separate from that for systemic perfusion, with the mean value being 13.1 ml/kg/min. Mean of minimum left superficial temporal arterial pressure was 51 mmHg, mean duration of SCP was 134 minutes, and mean of the lowest esophageal temperature was 17.9 degrees C. Blood pH was regulated with alpha-stat strategy. Arterial cannula for SCP was inserted directly into the vessels through a stab wound in most cases. In three of four patients in whom dissection extended to the branches, a balloon catheter was introduced through the lumen of the aortic arch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798701 TI - [Effects of amrinone on left ventricular function following open heart surgery- analysis with left ventricular pressure volume loops]. AB - The effects of Amrinone on cardiac function soon after extracorporeal circulation (ECC) were studied in 5 patients including mitral valvuloplasty, VSD closure, Fontan operation and coronary AV fistel closure. In all patients, left ventricular volume load decreased postoperatively. To evaluate the efficacy, we obtained left ventricular pressure-volume loops (P-V loop) before and after ECC and after intravenous administration of Amrinone (1 mg/kg) following ECC. P-V loops were produced by measuring left ventricular pressure using a Miller catheter which was retrogradely advanced from the ascending aorta into the left ventricle and by measuring left ventricular diameter to calculate left ventricular volume with Teichholtz' formula. Although no apparent difference of Emax was recognized before and after ECC, Emax increased from 3.2 +/- 2.5 mmHg/cm3 to 5.9 +/- 4.7 mmHg/cm3 after the administration of Amrinone. The left ventricular "systolic" pressure-volume area (PVA) which is the sum of stroke work (SW) and elastic potential energy decreased from 34.4 +/- 16.4 gm to 30.9 +/- 17.8 gm after Amrinone. No difference was also recognized in left ventricular end diastolic pressure. Ejection fraction increased from 50 +/- 17.5% to 56.1 +/- 17.3%. These results suggested that Amrinone could improve the left ventricular function without prominent change in myocardial oxygen consumption immediately after open heart surgery. PMID- 7798702 TI - [Coronary artery bypass grafting only with arterial grafts in patients with low left ventricular function]. AB - The advantage of arterial grafts in coronary artery bypass grafting (CABG) has been recognized and the application of these grafts has spread widely. But, the possibility of insufficient blood flow immediately after operation is pointed out. The present study was conducted in order to answer whether or not arterial grafts are applicable for patients with low left ventricular function. CABG only with arterial grafts was performed in 125 patients from December 1989 to October 1993. Comparison was made between L-group (n = 21) with a preoperative ejection fraction (EF) of 0.4 or less, and N-group (n = 104) with a preoperative EF of more than 0.4. The proportion of patients requiring postoperative IABP (33%:9%) and the incidence of mediastinitis (14%:3%) were higher in the L-group. But the mortality rate (5%:3%) or the postoperative NYHA stage (1.2:1.2) showed no significant difference between these two groups. This favorable result suggests that CABG only with arterial grafts was also useful in patients with low left ventricular function. PMID- 7798703 TI - [Reduction in cellular immunity in diabetics receiving coronary artery bypass grafting]. AB - We studied the changes in peripheral lymphocyte subsets, mitogen responsiveness, natural killer (NK) cell activity, and interleukin-2 (IL-2) production in patients with or without diabetes receiving coronary artery bypass surgery. Group I (GI): 9 diabetic patients comprising three on oral diabetics during therapy, two on insulin therapy, and four on alimentary therapy. Group II (GII): 12 non diabetic patients (borderline diabetics excluded). age, amount of blood transfusion, number of grafts, aortic cross-clamp time (ACC), cardio-pulmonary bypass time (CPB), and operative time (OP) did not significantly differ between the groups. Lymphocyte subsets were measured using monoclonal antibodies and IL-2 production was measured by radio-immuno assay using IL-2 labeled with I125. All variables were measured the day before, the day after, 3 days after and 7 days after the operation. The number of lymphocytes and their subsets (CD3+, CD+, CD8+, 4/8 ratio, IL-2R+) did not significantly differ between the groups, but in GI patients, the number of OKIa1 positive lymphocytes were significantly lower than in GII the day before and 7 days after the operation. II-2 production on the day after the operation was significantly (p < 0.05) reduced from the preoperative level in both groups. On 3 days, there was a significant difference (p < 0.05) between the two groups: IL-2 production in GI (3.1 +/- 2.6 U) was remarkably lower than in GII (6.6 +/- 4.0 U). IL-2 production in GII was significantly correlated to the number of CD4 positive lymphocytes, but this was not true in GI. Mitogen responsiveness to stimulation with PHA was not significantly different between the groups. NK cell activity on the first postoperative day was significantly reduced (p < 0.01) in the both groups, but there was no difference between the groups. The % change in IL-2 production (%IL 2) in GII on 3 days after the operation was significantly correlated to the amount of blood transfusion (r = -0.7, p = 0.0077) but that in GI was not. %IL-2 was not significantly correlated to ACC, CPB, OP, or age in both groups. This study clearly showed that diabetics who underwent coronary artery bypass surgery suffered depression of cellular immunity, in particular, IL-2 production, which might be a key factor in cellular immunity. It showed a decrease in helper T lymphocyte function after surgery, implying postoperative immunodeficiency in diabetics. PMID- 7798704 TI - [Monitoring of electroencephalogram during the operation under the extracorporeal circulation]. AB - Generally speaking, it is difficult to know the occurrence of brain complication until the patient becomes awake from anesthesia. But if we can detect the occurrence of of brain complication during the operation, we can start its therapy even during the operation. In order to detect the occurrence of brain complication during the operation under extracorporeal circulation (ECC), we monitored intraoperative electroencephalogram (EEG). Since June 1992, forty-two patients were operated on using ECC. Usual ECC was applied in 39 cases (Group-A), and circulatory arrest with retrograde cerebral perfusion was applied in remaining three cases (Group-B). We studied the amplitude of EEG using actual value (by Fujimori method), and compressed EEG acquired by slow-paper-feed recording. In terms of the frequency of EEG, we studied compressed spectral array (CSA). In Group-A, there was no brain complication identified after operation. Actual values of amplitude were 23 +/- 4.0 microV (before ECC), 19 +/- 4.0 microV (during ECC), 23 +/- 4.9 microV (after ECC). There was a significant decrease (p < 0.001) of amplitude during ECC compared with that before ECC. The ratio of amplitude during ECC to that before ECC (D/B ratio) was 0.82 +/- 0.16. The ratio of amplitude after ECC to that before ECC (A/B ratio) was 1.01 +/- 0.15. According to compressed EEG, it was observed that the amplitude changes following the up-down of esophageal temperature. In CSA, influence of esophageal temperature on the power spectrum of alpha and delta wave band was recognized. In Group-B, there was one brain complication identified after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798705 TI - [Result of sequential coronary artery bypass grafting only with arterial grafts]. AB - The indication of percutaneous transluminal coronary angioplasty is getting wide, and surgical case is getting more severe and more serious. We have, as a rule, performed bypass surgery only with arterial grafts and we have conducted sequential bypass surgery to cope with multiple vessel disease. Coronary artery bypass grafting (CABG) only with arterial grafts was performed in 120 patients from January 1991 to November 1993. Comparison was made between sequential group (n = 20 cases) and non-sequential group (n = 100 cases). The patency rate of sequential group was 98% (39 branches/40 branches). It was 96% (27/28) in the left internal thoracic artery (LITA) sequential group and 100% (12/12) in the right gastroepiplotic artery (RGEA) sequential group. There was no death. The patency rate of non-sequential group was 98% (248/253). It was 98% (95/97) in the LITA group, 97% (60/62) in the right internal thoracic artery (RITA) group, and 99% (93/94) in the RGEA group. Three patients (3%) died in hospital. Operation time, extracorporeal circulation time, and aortic crossclamp time was found to be shorter in the sequential group on two and three vessel bypass surgery. Because the patency rate of sequential bypass were favorable and the operating time could be reduced, sequential bypass method is thought to be usefull in CABG only with arterial grafts. PMID- 7798706 TI - [Comparison of duodenogastric reflux (DGR) to esophageal substitute between retro sternal route and posterior mediastinal route]. AB - To elucidate superiority of route among surgery of esophageal cancer with stomach tube, duodenogastric reflux (DGR) were examined in nine cases of retro-sternal bypass (RS) and 18 cases of posterior mediastinal group (PM) by means of questionnaire of reflux esophagitis, esophageal transit scintigram and 24 hour pH monitoring to those patients. Firstly, in order to readily compare the two groups, each section of reflux symptoms was expressed as a brief score by dividing each symptom into strength (0-3) and frequency (0-3). Mean score of reflux sensation was less in RS than in PM significantly (0.9 vs. 2.9, p < 0.01). The median value showed that patients in PM had much DGR symptoms than those in RS significantly (8.5 vs. 5.5, p < 0.01). In esophageal transit scintigram, TcO4- (85 MBq) was counted by gamma camera at the upper (ROI-1), center (ROI-2), and lower (ROI-3) sites of the sternum bone in the upright position. The descending time of RI peak from ROI-1 to ROI-3 in RS was shorter than PM (2.1 sec vs. 3.9 sec, N.S.). At ROI-2, clearance rate of RI in RS was similar to that in PM. At ROI-3, clearance rate of RI in RS was better than that in PM significantly (80.0% vs. 49.6%, p < 0.05). Scintigram revealed RI stasis in PM, which might be presumably concerned to DGR. Intragastric pH was measured continuously 5 and 15 cm below the esophagogastrostomy using 2-channeled antimony pH sensors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798707 TI - [Preliminary clinical results of surgery for type A acute aortic dissections using gelatin-resorcin-formaldehyde glue]. AB - We used gelatin-resorcin-form-aldehyde (GRF) glue to fuse the false lumen of type A acute aortic dissection in four patients. All were operated on within 3-24 hours after onset, and gluing of the two cylinders of the dissecting aorta could be done safely in a short time. Initial intimal tears were located in the transverse aorta in three patients and in the proximal descending aorta in one. Simple transection and end-to-end anastomosis of the ascending aorta was done for the first two cases. But in the last two patients, we resected the intimal tear in the transverse aorta and applied GRF glue to the stump of the aortic arch and to that of the aortic root, followed by graft replacement of the ascending aorta. There were no hospital deaths. But we had to reoperate on one patient five months after the first operation due to potentially residual dissection in the aortic root. GRF glue is a very useful adhesive for acute aortic dissection operations, but further refinement of the operative technique using it is necessary. PMID- 7798708 TI - [Pre-operative screening tests for lung cancer using the analysis of expired gas with exercise testing--principally VO2 max/m2]. AB - The analysis of expired gas with exercise testing was conducted preoperatively with lung cancer patients in order to examine the relationship between maximum oxygen consumption (VO2 max) and postoperative complications, determining the cut off of VO2 max/m2. The usefulness of the test as a preoperative screening test for both pulmonary ventilation and circulation was evaluated in comparison to pulmonary ventilation tests with spirometry and pulmonary circulation tests with Swan-Ganz catheter. Preoperative VO2 max/m2 was calculated from VO2 max in 111 patients with lung cancer who underwent lobectomy of more than one lobe. Also preoperatively conducted were pulmonary ventilation tests by spirometry and pulmonary circulation tests using the Swan-Ganz catheter to measure VC, %VC, FEV1.0, FEV1.0%, mean pulmonary arterial pressure (PPA) and cardiac output coefficient (C.I.). Form theses measurements, VC/m2, FEV1.0/m2 and total pulmonary vascular resistance (TPVR) were calculated. After the cut-off values of VO2 max/m2 were set tentatively at three stages, 600, 650 and 700 ml/min/m2 based on the incidence of postoperative complications, the 111 patients were divided into two groups in each cut-off value; one with VO2 max/m2 greater than the cut off value and the other less than the cut-off value. Comparison of measurements obtained by spirometry between the two groups disclosed significant differences (p < 0.001) in VC/m2, %VC and FEV1.0/m2 in all cut-off values. Similarly, comparison of measurements obtained using the Swan-Ganz catheter between the two groups yielded significant differences (p < 0.05 to p < 0.01) in PPA and TPVR in all cut-off values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798710 TI - [Study on development of linear-traction type skeletal muscle powered pump]. AB - We successfully developed Linear-Traction Type Skeletal Muscle Powered Pump (LSMPP). Unlike the Insertion-Type SMPP (ISMPP), previously used by us, in which a polyurethane chamber is inserted between skeletal muscle and chest wall, this pump can utilize the traction of muscle fiber in a linear direction. This pump also enabled us to obtain a sufficient flow with a low preload by the use of a spring for the filling of the pump. Comparison was made between the measurement of flow using the origin side of Latissimus Dorsi Muscle (o-group) (n = 6) and that using the upper arm side (i-group) (n = 6), both measured with the Linear Traction Type equipment, and the result obtained with the ISMPP (s-group) (n = 6). Under a rate of 60 beat/min and a preload of 40 mmHg, the flows (ml/min) of o group, i-group and s-group were 668.0 +/- 108.0, 1202 +/- 478.6 and 620.0 +/- 188.0, respectively. In i-group (n = 6), different rate, preload and spring constant were given to examine how the flow would vary with them. Mean flow (Mean +/- Std ml/min) was 815.0 +/- 378.0 at 60 beat/min, significantly different in comparison with that of 80 beat/min and that of 100 beat/min. For 40, 30 and 20 mmHg of preloads, mean flows were 877.0 +/- 366.0, 625.0 +/- 311.0 and 422.0 +/- 270.0, respectively. This showed that, as far as the rate remains low, even low preload can provide some 30% of the cardiac output of a dog as compensate cardiac flow. In contrast, there were no significant differences in mean flow with spring constants such as 0, 80, 160, 240 and 320 g/cm. PMID- 7798709 TI - [The efficacy of both antegrade and retrograde cardioplegia in coronary artery bypass surgery]. AB - We evaluated the efficacy of the cardioplegic myocardial protection by combining antegrade cardioplegic induction via the aortic root with retrograde cardioplegia via the coronary sinus in patients who had LAD stenosis or occlusion with collateral circulation. In study I, forty-six patients were divided into two groups: antegrade group (group A; 32 cases), which were perfused by only antegrade fashion via the aortic root, and bi-directional group (group B; 14 cases), which were perfused by combining antegrade with retrograde fashion. In study II, patients were divided into four groups: 32 cases in group A were divide into three subgroups by the direction of the collateral circulation to LAD in preoperative coronary angiograms: group I (antegrade collateral circulation; 18 cases), group II (retrograde collateral circulation; 7 cases), group III (99% stenosis with delayed filling; 7 cases) and group B was as group IV. Myocardial injury was assessed with the use of enzyme indexes (total CPK, CPK-MB, %MB, peak CPK, peak CPK-MB and peak % MB) in study I and study II. There was no significant difference between the two groups in study I and the four groups in study II in terms of patients' profile, graft materials, number of grafts, aortic cross clamping time, total cardiopulmonary bypass time and surgical results. Total CPK level in group B was significantly lower (p < 0.05) compared with group A at the point of 12 hr and 1 day after surgery and peak CPK level was also significantly lower (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798712 TI - [Intraoperative pulmonary angioscopy to undergo pulmonary embolectomy for acute massive pulmonary embolism]. AB - An urgent pulmonary embolectomy on a patient under intraoperative angioscopy for the treatment of massive pulmonary embolism was performed and successfully saved the patient. The case was a 19-year-old man who had been bedridden over along period of time. He developed pulmonary embolism immediately after the initiation of walking rehabilitation. Although anticoagulation therapy was immediately carried out, hemodynamics deteriorated, and as a result, it became necessary to treat this patient with the urgent surgical procedure. Under extracorporeal circulation with the clamping of the aorta, the pulmonary artery was opened. Following embolectomy for the left pulmonary artery, the right pulmonary artery, where the presence of clots had not been confirmed with the naked eye, was inspected using an flexible fiberoptic choledochoscope 4.9 mm in diameter. Consequently, amount of clots were removed using forceps or an aspirating tube. The patient recovered from hypoxemia after surgery. The use of intraoperative angioscopy in the pulmonary artery proved to be very useful to examine the presence of emboli up to tertiary branches of pulmonary artery. PMID- 7798711 TI - [Lung resection for lung carcinoma with idiopathic interstitial pneumonia]. AB - Of 12 patients who underwent lung resections for lung cancer with idiopathic interstitial pneumonia (IIP), eight patients survived and four patients died due to acute exacerbation of IIP after the operation. The preoperative values for percent forced vital capacity, predicted postoperative percent vital capacity, percent one-second forced expiratory volume index and serum level of C-reactive protein were significantly different between the group of patients who survived and that of having died. Three days after the operation, the percentage of lymphocytes among leukocytes and serum level of lactate dehydrogenase in the two groups were both significantly different. These findings showed that the operative strategy for patients with lung cancer and IIP needs specifically careful consideration for operative procedure, and preoperative serum levels of C reactive protein and postoperative lactate dehydrogenase and the percentage of lymphocytes in leukocytes would be useful in evaluation of the severity of IIP. PMID- 7798713 TI - [A case of bronchogenic cyst in the esophageal wall]. AB - A 73-year-old man with a right aortic arch was admitted because of stridor and dyspnea. We diagnosed a cervico-mediastinal cyst associated with bilateral recurrent laryngeal nerve palsy. Median sternotomy revealed a cystic tumor located in the esophageal wall. Microscopic examination of the resected cyst showed cartilage, smooth muscle and mucous gland, so the final diagnosis was bronchogenic cyst. The bilateral recurrent laryngeal nerve palsy was caused by chronic pressure from the cyst. Mediastinal cysts should be found and treated as early as possible, because these cysts may sometimes cause fatal complications. PMID- 7798714 TI - [A case of surgical treatment of Swyer-James syndrome]. AB - Swyer-James syndrome was usually diagnosed on the past history and the radiologic features, and almost all the cases were followed by the conservative therapy. Therefore, the examination of the pathologic features was rare. We recently experienced a patient with Swyer-James syndrome, who had a history of respiratory infection from his childhood onward and whose chest radiograph revealed hyperlucency of the right lower lung field. A standard right middle and lower lobectomy was performed. Histological examination of the resected specimens revealed hypoplasia of alveoli and pulmonary artery. PMID- 7798715 TI - [Nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome]. AB - A successful nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome is reported. A 36-year-old woman developed a DeBakey type-I aortic dissection in October 1987. We replaced the ascending aorta and resuspended the aortic valve urgently, when she had not been diagnosed with Marfan's syndrome. In August 1989, we replaced the distal portion of the descending aorta and the infra-renal abdominal aorta because of dilatation in the diameter of these regions. In September 1990, she had sudden severe chest pain. Computed tomography and Doppler ultrasonography revealed that a new aortic dissection developed in the aortic arch and the descending aorta (three-channeled dissection) and that the new false lumen compressed the true and the old false lumens obstructing the blood flow to the abdominal aorta. She was immediately placed an axilo-femoral bypass, and in January 1991 she underwent the arch and descending aorta replacement using permanent bypass to the supra-aortic branches and partial extracorporeal circulation (first reported by Larmi et al). Postoperative course was satisfactory, and she has been well at 3 years after the operation. Because progressive dilatation of an untreated dissecting aorta is common in patients with Marfan's syndrome, aggressive replacement of the diseased aorta is indicated in these patients. PMID- 7798716 TI - [A case of metastatic lung tumor from acinic cell tumor of the parotid gland]. AB - A 59-year-old man with metastatic lung tumor from acinic cell tumor of the parotid gland was reported. Five years after resection of the parotid tumor, the abnormal shadow on chest X-ray film was detected in the mass screening. The tumor was located in S10c of the right lung, and resected by partial lung resection. As pathological findings showed the same histology between the parotid gland and the lung, we diagnosed the metastatic lung tumor from acinic cell tumor of the parotid gland. Acinic cell tumor shall be slowly growing and occasionally developing the pulmonary metastasis. So, we have to carefully follow the patient in long-term periods. PMID- 7798718 TI - [A case report of primary fibrosarcoma originated in the heart invading adjacent organs ]. AB - A rare case of cardiogenic fibrosarcoma is reported. A 66 y.o. male with dyspnea, cough and fatigue was examined. B-mode echo, MRI, and angiography disclosed a large tumor in the left atrium. A large fibrosarcoma and 2 cm of the left atrial wall around the tumor pedicle were removed. The atrial defect and right lower pulmonary vein were repaired with a patch. Four months later, the tumor recurred in the right lung, mediastinum, and left atrium. The tumor, middle and lower lobes of the right lung, and part of the left atrial wall were excised. One year after the first operation, the patient died of air way obstruction due to another recurrence of the fibrosarcoma in the left lung, esophagus, and mediastinum. Cardiogenic fibrosarcoma invading outward for the mediastinal organs is rare. PMID- 7798717 TI - [A case of ACTH-releasing lung carcinoid tumor presenting Cushing's syndrome]. AB - The patient was a 47-year-old female who had undergone hypophysectomy due to Cushing's syndrome when 46 years old. In April 1992, about 1 month after the operation, chest CT-scan revealed a lesion of 8 x 8 mm in size in the right upper lobe. A high value of serum ACTH was obtained from the A3b wedge blood by cardiac catheterization. She was operated on suspicion of ACTH releasing lung tumor. During the operation, it was histologically diagnosed as lung carcinoid by a frozen section of the lesion. In addition, ACTH of the blood obtained from the right superior pulmonary vein was as high as 37,300 pg/ml, but that in the right main pulmonary artery or the radial artery was 850-970 pg/ml. Right upper lobectomy with dissection of mediastinal lymph nodes was so performed. Post operative value of serum ACTH was significantly decreased. She was in good course, and is still asymptomatic 8 months after the operation. PMID- 7798719 TI - [A case of pseudoxanthoma elasticum underwent coronary artery bypass grafting]. AB - A case of pseudoxanthoma elasticum (PXE) underwent coronary artery grafting is reported. Coronary angiography of a woman with age of 41 with PXE revealed three vessels lesions. Coronary artery bypass grafting using saphenous vein grafts was performed. The left internal mammary artery was not able to use because of obstruction. Her postoperative course is uneventful for 3 years to date. Histological examination of a segment of ascending aorta revealed changes of PXE underwent CABG is extremely rare. This is the third reported case in Japan. PMID- 7798720 TI - [A case-report of pacemaker malfunction caused by dry pocket after replacement of pulse generator]. AB - Pacemaker malfunction was attributed to the increasing in impedance to current flow caused by a pocket of air separating the anodal contact plate of a unipolar generator from the overlying connective tissue (so-called dry pocket). Lack of capture was noted just after replacement of pulse generator. The malfunction was permanently corrected by bediside infusion of saline to pacemaker pocket. PMID- 7798721 TI - [A successful use of VAS for bridge to heart transplantation after oversea transportation in a 18-year-old patient with dilated cardiomyopathy]. AB - An 18-year-old boy with dilated cardiomyopathy developed a relatively rapid deterioration and went into severe congestive heart failure. After short-while use of percutaneous cardiopulmonary support system (PCPS) and IABP, LVAS was indicated because of persisting low cardiac output syndrome and deterioration of organ functions. An LVAS (TOYOBO) was implanted on June 26, 1992 in a fashion of left atrium to ascending aorta bypass. Satisfactory circulatory support (flow rates of 4-5 L/min) was achieved resulting in complete recovery of the organ functions. After two months of LVAS support, the patient was transported to U.S.A.. The LVAS system was working well without any problems during 17 hrs flight under low atmospheric pressure (0.8 atm) in the plane. The patient successfully underwent heart transplantation (HTx) at Texas Heart Institute after 119 days support of LVAS. The patient is doing well enjoying active life after HTx. This is the first case of successful bridge use of extracorporeal LVAS to HTx in Japan. PMID- 7798722 TI - [A case of chronic hemorrhagic pyothorax treated by extraperiosteal air plombage method]. AB - A 64-year-old female patient was admitted with severe exertional dypnea. She had undergone left pneumonectomy because of lung tuberculosis at the age of 31. Her chest X-ray showed total opacity of the left hemithorax and mediastinal deviation to the right. The examination of the pleural effusion revealed neither malignant cells nor micro-organisms. She underwent surgery, by extraperiosteal air plombage method, successfully. Five months after the operation, her lung function and chest X-ray improved dramatically and exertional dyspnea was diminished. We conclude that the extraperiosteal air plombage method is a useful technique for patients with chronic hemorrhagic pyothorax. PMID- 7798723 TI - [A case report of tricuspid valve valvoplasty for tricuspid endocarditis]. AB - A successful repair of tricuspid valve insufficiency due to endocarditis related to VSD is reported. Combined quadrangular resection and repair of anterior leaflet, pericardial patch plasty of anterior-septal commissure, Carpentier ring annuloplasty and VSD closure was performed with good clinical results. PMID- 7798724 TI - [A case of mitral valve replacement with chronic idiopathic thrombocytopenic purpura after high-dose immunoglobulin infusion]. AB - A 60-year-old female patient diagnosed as having mitral stenosis with chronic idiopathic thrombocytopenic purpura (ITP), with a platelet count of 6.8 x 10(4)/mm3, was scheduled to undergo mitral valve replacement. High-dose immunoglobulin infusion (400 mg/kg/day for five days) was begun four days before the operation and increased the platelet count to 9.1 x 10(4)/mm3 just before the operation. Intraoperative hemostasis was excellent, and the postoperative course was uneventful. High-dose immunoglobulin therapy appears to be a first choice for controlling hemorrhagic tendency in ITP patients undergoing heart surgery. PMID- 7798725 TI - [Congenital esophago-bronchial fistula in adult--report of a case]. AB - A 52-year-old man had been having cough on drinking water since 30 years. He coughed out blood 20 years ago. Chest roentgenogram showed the infiltrating shadow in the right lower lung field and the left hilum. Chest computed tomogram in the left atrium level showed fistulous communication between the bronchus and the esophagus and cavity lesion. Esophagogram showed fistulous communication between the bronchus (rt. B7) and the middle third of the esophagus. Bronchogram showed the stenotic lesion of the right B7a and B*. And abnormal bronchus was revealed and fistula was suspected. The orifice of the fistula was seen by esophageal endoscopy. Through the right posterolateral thoracotomy, fistelectomy and covering with pleural flap over the esophageal suturing site were performed. Histologic finding of the resected specimen revealed fistula's wall composing of smooth muscle lined with squamous cell layer. This case is categorized as Braimbridge type II. The postoperative course was uneventful and the patient is now in free of complaints at the 6th month's P.O.D. PMID- 7798727 TI - Genetic teaching for the retinoblastoma patient. AB - Retinoblastoma is the most common primary intraocular tumor in children. Retinoblastoma can be hereditary (familial) or nonhereditary (nonfamilial). Nurses who have an understanding of the genetic patterns for retinoblastoma can participate in the counseling of these patients. A chart is provided as a tool for teaching patients about family patterns of retinoblastoma. PMID- 7798726 TI - Electrophysiology testing and the ophthalmic registered nurse. AB - Ophthalmologists employ electrophysiologic testing to diagnose and manage a variety of ocular conditions. The most common reason these tests are performed is to diagnose inherited vitreoretinal diseases. Patients of all ages may require electrophysiologic testing. The purpose of this article is to provide the ophthalmic registered nurse with a working knowledge of the three most commonly used electrophysiologic tests. We will provide background and practical information on how we perform electroretinography (ERG), electroculography (EOG), and dark adaptometry. Knowledge of the basics of this specialized testing will allow the ophthalmic nurse to provide more information for the patient. This knowledge will hopefully reduce patient anxiety and with better cooperation produce more accurate test results. PMID- 7798728 TI - Complications of indirect laser photocoagulation. AB - Potential complications of indirect laser photocoagulation for retinopathy of prematurity are: corneal burn; iris burn; lens burn; choroidal hemorrhage or neovascularization; inadvertent photocoagulation of fovea; preretinal membrane formation; late onset retinal detachment; and retinal, preretinal, or vitreous hemorrhage. PMID- 7798730 TI - The future through high-tech spectacles. PMID- 7798731 TI - Role delineation study for ophthalmic registered nurses. PMID- 7798729 TI - Overview and new technology in cyclodestructive procedures. AB - When all medical and surgical measures have failed to lower intraocular pressure (IOP) in patients with severe and uncontrolled glaucoma, ophthalmologists must turn to cyclodestructive procedures to decrease aqueous production. Several months ago, the FDA (Food and Drug Administration) came through with an approval for a new technology in cyclophotocoagulation therapy. The IRIS Medical G-Probe used in conjunction with a semiconductor diode laser may be the superior alternative to previously available cyclodestructive techniques for which ophthalmologists have been searching. PMID- 7798732 TI - "Stones in the eye": post cataract suture irritation--a transcultural study from Sierra Leone, West Africa. AB - A retrospective study of 1214 outpatients in Sierra Leone, West Africa was done to answer the question, "What is the visual acuity following extracapsular cataract extraction (ECCE) with an intraocular lens (IOL) for patients in a developing country?" Only 24% achieved uncorrected pseudophakic visual acuity of 20/20 to 20/50. Additionally, postoperative complications and patient complaints were tracked. Results showed suture irritation was less prevalent in those patients when 10-0 nylon suture was used, cut close, and the knot rotated and buried. PMID- 7798733 TI - [Internal medicine in the 21st century]. PMID- 7798734 TI - [Basic study of hematopoietic stem cells and the clinical application]. PMID- 7798736 TI - [Basic and clinical study of Helicobacter pylori infections]. PMID- 7798735 TI - [Clinical study of AIDS]. PMID- 7798738 TI - [Takatsuki disease found in Japanese patients]. PMID- 7798737 TI - [Basic and clinical study of Alzheimer-type dementia]. PMID- 7798739 TI - [Autoimmune insulin syndrome found in Japanese patients]. PMID- 7798740 TI - [HTLV-I associated myelopathy found in Japanese patients]. PMID- 7798741 TI - [Vascular endothelial cells and arteriosclerosis]. PMID- 7798742 TI - [Vascular smooth muscle cells and arteriosclerosis]. PMID- 7798744 TI - [Cytokines, growth factors and arteriosclerosis]. PMID- 7798743 TI - [Macrophages and arteriosclerosis]. PMID- 7798745 TI - [Recent advance on chemotherapy of leukemia]. PMID- 7798746 TI - [Optimal administration of 5-FU and cisplatin based on biochemical modulation in the treatment of non-resectable non-small cell lung carcinoma]. PMID- 7798748 TI - [Progress on chemotherapy in patients with non-resectable stomach cancer]. PMID- 7798747 TI - [Clinical application of adoptive immunotherapy in patients with progressive lung cancer]. PMID- 7798749 TI - [Angiotensin II-induced hypertension chemotherapy in patients with progressive non-resectable digestive system cancer]. PMID- 7798750 TI - [Treatment of progressive non-resectable hepatoma]. PMID- 7798751 TI - [Proton radiation therapy of non-resectable liver neoplasm]. PMID- 7798752 TI - [Epidemiologic study of obstructive sleep apnea syndrome]. PMID- 7798753 TI - [Physiopathology of sleep apnea]. PMID- 7798754 TI - [Diagnosis of sleep apnea]. PMID- 7798755 TI - [Symptoms associated with sleep apnea]. PMID- 7798756 TI - [Treatment of obstructive sleep apnea syndrome]. PMID- 7798757 TI - [Diagnosis of anemia--analysis of erythrocyte ferritin]. PMID- 7798758 TI - [Recent progress on the diagnosis and therapy of secondary hypertension]. PMID- 7798759 TI - [Cardiac sudden death]. PMID- 7798760 TI - [Respiratory failure and respiratory muscle fatigue]. PMID- 7798762 TI - [Prevention and therapy of osteoporosis]. PMID- 7798761 TI - [Non-invasive therapy of Cushing's syndrome]. PMID- 7798763 TI - [Treatment of diabetic nephropathies]. PMID- 7798764 TI - [Basic and clinical study of alcoholic liver and digestive system injuries]. PMID- 7798765 TI - [Dystonia and botulinum toxin therapy]. PMID- 7798767 TI - [Blood platelet disorders]. PMID- 7798766 TI - [Lipoproteins and coronary arteriosclerosis]. PMID- 7798768 TI - [Roll of endothelin-1 in mechanism of cell communication system]. PMID- 7798769 TI - [Insulin receptors and diabetes mellitus]. PMID- 7798770 TI - [Viral myocarditis]. PMID- 7798771 TI - [Antisense therapy]. PMID- 7798772 TI - [Basic and clinical study of bacterial biofilm]. PMID- 7798773 TI - [Mitochondrial encephalomyopathies]. PMID- 7798774 TI - Antitrust reform: equality at the bargaining table. PMID- 7798775 TI - ECG of the month. Dead beats. Pacemaker rhythm. PMID- 7798776 TI - Disorders of taste and smell. AB - Chemosensory dysfunction involves deficits in taste or smell. Aberrations in these senses can be quite distressing to the patient and can negatively impact on nutritional well-being. A thorough history and physical examination are important in isolating the etiology of the sensory loss from the numerous causes of taste and smell disorders. The diagnosis can be simplified by the fact that only a few causes (nasal and sinus disease, viral-induced loss, and head trauma) are responsible for the vast majority of chemosensory dysfunctions. Therapy is limited, but one should be aware of the existing medical and surgical treatment modalities. PMID- 7798777 TI - A five-step approach to settling a dispute over futile care. PMID- 7798778 TI - The journal 100 years ago. October 1844-1894. PMID- 7798779 TI - Ceftazidime as monotherapy for fever and neutropenia: experience in a community hospital. AB - Fever and neutropenia is occurring in a wider variety of clinical settings, and the proper antibiotic therapy for its treatment is an area of debate. Our study is a retrospective analysis of the experience of the Oncology Division of the Medical Center of Baton Rouge, which used ceftazidime as monotherapy in the empiric treatment of fever and neutropenia. A total of 53 episodes in 38 patients were studied. Using ceftazidime as monotherapy in our study population was associated with an 8% mortality rate, indicating that monotherapy is a viable option for the treatment of fever and neutropenia. PMID- 7798781 TI - Progression of experimental chronic renal failure: does platelet-activating factor play a role? PMID- 7798780 TI - Air quality and respiratory functioning in children with pulmonary disorders. AB - This study was conducted to examine the relation between daily ambient air conditions, contaminants (eg, aeroallergens such as mold spores and pollen), and respiratory health indices of children with respiratory disorders (eg, asthma) residing in metropolitan Baton Rouge, Louisiana. Daily measures of peak expiratory flow rate (PEFR), respiratory symptoms, and other indices of health were monitored as subjects went about their normal daily activities. The results of this study suggest that high summer temperatures had the greatest impact on children's health status and activity level, with humidity and mold counts also contributing significantly to a decline in respiratory health indices. PMID- 7798782 TI - Endotoxin transfer during dialysis: less than meets the eye? PMID- 7798783 TI - Direct effects of the adrenergic system on cardiac hypertrophy: molecular analysis of the heterotopically transplanted heart. PMID- 7798784 TI - Tumor necrosis factor and endothelins: team players in shock? PMID- 7798785 TI - Cellular and molecular basis of renal repair in acute renal failure. AB - Experimental data suggest that the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent on predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair in ischemic and nephrotoxic acute renal failure and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. PMID- 7798786 TI - Fibrogenesis and type I collagen gene regulation. PMID- 7798787 TI - Apoptosis: physiologic cell death. PMID- 7798788 TI - Behavioral neurophysiology of the motor cortex. AB - The study of the motor cortex in behaving monkeys during the past 20 years has provided important information on the brain mechanisms underlying motor control. With respect to reaching movements in space, several aspects of motor cortical function concerning the specification of the direction of movement have now been elucidated and are reviewed in this article. The activity of single cells in the motor cortex is broadly tuned with respect to the direction of reaching, so that the discharge rate is highest with movements in a preferred direction and decreases progressively with movements made in directions more and more away from the preferred one. Thus the neural command for the direction of reaching can be regarded as an ensemble of cell vectors, with each vector pointing in the cell's preferred direction and having a length proportional to the change in cell activity. The outcome of this population code can be visualized as a vector that points in the direction of the upcoming movement during the reaction time, during an instructed delay period, and during a memorized delay period. Moreover, when a mental transformation is required for the generation of a reaching movement in a different direction from a reference direction, the population vector provides a direct insight into the nature of the cognitive process by which the required transformation is achieved. PMID- 7798789 TI - Platelet-activating factor receptor antagonist improves renal function and glomerular lesions in renal ablation. AB - In the renal ablation model hemodynamic changes, glomerular hypertrophy, and the release of inflammatory mediators contribute to structural damage and functional changes. Platelet-activating factor (PAF) has both hemodynamic and immune mediating properties. We therefore examined the role for a PAF receptor antagonist (WEB 2170) on glomerular hemodynamic function, albuminuria, and structural alterations in a rat model of renal ablation (Nx). WEB 2170 treatment was started 10 weeks after renal ablation, and the variables were assessed at 36 weeks after surgery. WEB 2170 significantly improved inulin and PAH clearances at 36 weeks (inulin clearance: Nx, 182 +/- 28 microliters/min/100 gm body weight; Nx plus WEB, 284 +/- 19 microliters/min/100 gm body weight; p < 0.05; PAH clearance: Nx, 718 +/- 85 microliters/min/100 gm body weight; Nx plus WEB, 1215 +/- 103 microliters/min/100 gm body weight; p < 0.05). Glomerular prostaglandin E2 (PGE2) formation was significantly increased in nephrectomized rats treated with WEB 2170 when compared with nephrectomized animals not treated (PGE2: Nx, 103 +/- 16 pg/min/mg protein; Nx plus WEB, 182 +/- 19 pg/min/mg protein; p < 0.01). The PAF receptor antagonist did not change albuminuria (Nx, 205 +/- 56 mg/24 hr; Nx plus WEB, 178 +/- 48 mg/24 hr). Glomeruli of rats treated with WEB 2170 had significantly fewer sclerotic lesions at 36 weeks when compared with untreated animals (Nx, 36.5 +/- 4.4%; Nx plus WEB, 19.3 +/- 3.7%; p < 0.05). The results demonstrate that a PAF receptor antagonist significantly improves whole kidney clearances and glomerular morphology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798790 TI - The role of plasma in the transfer of Escherichia coli cytokine-inducing substances across high-flux cellulosic membranes. AB - It has been previously reported that the presence of plasma in the blood side compartment of cellulosic membranes enhances the transfer of cytokine-inducing substance (CIS) present in the dialysate compartment. This apparent enhancement could either be a result of (1) improved membrane permeability to CIS, (2) transfer of plasma components to the dialysate compartment thereby causing dissaggregation of CIS with subsequent backtransfer to the blood compartment, or (3) improved detection of transferred CIS resulting from carryover of plasma from the blood compartment to the mononuclear cell incubation step. An in vitro dialysis model was used to determine which of the above mechanisms were involved in this phenomenon. Results showed that enhanced detection of CIS could not be attributed to improved detection resulting from carryover plasma. Both addition of plasma to the dialysate compartment of pre-exposure of membranes to plasma resulted in enhanced transfer of CIS in a fashion similar to that seen when plasma was added to the blood compartment. These observations suggest that the transfer of Escherichia coli culture filtrate-derived CIS across cellulosic membranes is enhanced on exposure to 10% plasma because of alterations in the permselectivity of the membrane. PMID- 7798791 TI - Effects of adrenergic agonists on the growth and gene expression of the transplanted heart. AB - Cardiac growth occurs in response to changes in hemodynamic demand and results primarily from cellular hypertrophy without cellular hyperplasia. In addition to changes in cardiac work, various reports have demonstrated that adrenergic stimulation, specifically of the alpha 1 adrenergic receptor of cultured myocytes, can produce changes in cardiac-specific gene expression and increases in protein synthesis and cell growth. To study the effects of adrenergic stimulation in the absence of alterations in cardiac work we have used the model of the heterotopically transplanted heart, which is a spontaneously beating, vascularly perfused, and histologically normal heart that is hemodynamically unloaded. Seventy-two hours after transplantation, the hemodynamically unloaded transplanted heart had decreased in size by 20% when compared with the control host heart that was growing in situ. Treatment with either the alpha-adrenergic agonist phenylephrine (2.5 mg/kg/day) or the beta-adrenergic agonist isoproterenol (250 micrograms/kg/day) while increasing the spontaneous heart rate had no effect on the size of the transplanted heart. Simultaneous measurements demonstrated that both of these drugs produced a 10% increase in weight of the corresponding hemodynamically loaded host heart. We previously demonstrated that cardiac unloading caused a change in the expression of the myosin heavy chain (MHC) genes with a significant increase in the beta MHC isoform. In the present studies treatment with either isoproterenol or phenylephrine did not alter MHC gene expression either in the in situ host or transplanted hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798793 TI - Bacterial characterization in Staphylococcus epidermidis septicemia. AB - An analysis of the in vitro characteristics of Staphylococcus epidermidis strains isolated from patients with true S. epidermidis septicemia was undertaken. From a potential population of 921 cultures from adult patients with coagulase-negative bacteremia, highly defined selective criteria limited the population to 20 patients with S. epidermidis sepsis, from whose blood cultures the study organisms were isolated. Another population of 11 S. epidermidis blood isolates, clinically determined to be contaminants, were tested as a control group. In vitro assays performed on all isolates included slime quantification, hydrophobicity, surface hexoses, and capsule presence. Murine spleen phagocytosis of intravenously administered isolates was measured in vivo. The assayed quantity of cell-associated bacterial hexose sugars positively correlated with organism virulence to the host (p = 0.02). This bacterial population was also low in slime but varied as to the presence of capsule and ease of phagocytosis. Permanent catheter-bearing patients' bacteria were somewhat more hydrophobic (p = 0.07). We conclude that in vitro assays can differentiate bacteremic cultures from contaminants and that the characteristic that best relates to host toxicity in these S. epidermidis isolates was bacterial cell surface-associated carbohydrate. PMID- 7798792 TI - Big-endothelin release in baboon bacteremia is partially TNF dependent. AB - Big-endothelin (big-ET) is one of the endothelium-derived vasoactive substances that plays an important role in regulating the vascular tone. Because the role of this agent in bacteremia remains unknown, we investigated whether bacteremia induces the release of big-ET in a subhuman primate model and whether tumor necrosis factor (TNF) is an important mediator of big-ET release. To study this, we infused 8 male baboons (17 to 19 kg body weight) intravenously for 2 hours with Escherichia coli (5 x 10(8) CFU/kg) and observed them for 72 hours. Plasma was obtained at various intervals and assayed for big-ET by using immunoassay. Four bacteremic animals given vehicle only showed a peak big-ET plasma concentration of 15.1 +/- 4.6 fmol/ml at 10 hours, as compared with a baseline concentration of 0.9 +/- 0.5 fmol/ml. Administration of anti-TNF monoclonal antibodies (CB6, 15 mg/kg) 2 hours before E. coli infusion in additional animals prevented the rise in plasma TNF levels (5.7 +/- 2.5 ng/ml versus nondetectable) and significantly (p < 0.01) attenuated the release of big-ET. Hemodynamic measurements revealed the typical pattern of sepsis, with generally more stable circulatory conditions in the anti-TNF-treated animals. Moreover, the mortality rate decreased from 100% to 0% with anti-TNF treatment. These studies, therefore, lead us to conclude that TNF, directly or indirectly through another mediator, plays an important role in the endothelin production/release during bacteremia and that neutralization of circulating TNF appears to be beneficial for improving the survival after bacteremia. PMID- 7798794 TI - Sweat electrolytes in patients with advanced renal failure. AB - The sweat gland has some similarity with the convoluted tubules of the kidney. Little is known about sweat secretion and electrolyte content of sweat in the uremic gland. A pilocarpine ionotophoresis sweat test was performed in 40 patients with advanced renal failure (RF). Sweat secretion was measured and analyzed for Na, K, and Cl and correlated to blood parameters, type, and duration of dialysis. The sweat weight was significantly lower in all RF patients when compared with this parameter in healthy controls (p < 0.0001). No difference was noted between patients undergoing hemodialysis, those undergoing continuous ambulatory peritoneal dialysis, and those not undergoing dialysis. Men sweated more than women among RF patients and among controls (p < 0.0001). An inverse correlation was found between sweat weight and blood calcium levels (p < 0.001). Sweat K concentration was significantly higher (p < 0.0001) in patients with RF than in healthy controls, while the concentrations of Na and Cl were similar. Several mechanisms are suggested as possible explanations for these changes. PMID- 7798795 TI - Evaluation of the significance of elevated levels of systemic and localized tumor necrosis factor in different animal models of inflammation. AB - Elevated tumor necrosis factor (TNF) levels have been reported in various models of acute and chronic inflammation and used by many investigators to determine the stage of disease and effectiveness of treatment. Because of the documented involvement of TNF in the mechanism of septic shock, experiments were done to determine whether serum TNF levels paralleled the pathology in endotoxic shock and other models of inflammation. When mice received an intraperitoneal injection of lipopolysaccharide, serum TNF levels increased dramatically, peaking 90 minutes after injection. In a dose-response experiment with lipopolysaccharide alone, we found no correlation between serum levels of TNF and survival rate of mice. All three lipopolysaccharide concentrations resulted in comparable elevations of serum TNF, yet only in the high-dose group did the animals die. In a second model of endotoxic shock, TNF-alpha levels in serum were again compared with the survival rate of mice receiving lipopolysaccharide plus galactosamine. As in the first model, we found no relationship between the level of TNF in mouse serum and mouse survival rate. The two lowest concentrations of lipopolysaccharide/galactosamine induced identically low levels of serum TNF, yet in one group all of the animals survived and in the other all died. Discrepancies between serum TNF level and mortality rate were also seen in drug treatment experiments. GI 147404X, a standard phosphodiesterase type IV inhibitor, inhibited lipopolysaccharide/galactosamine-induced elevation of serum TNF by 90% at doses of 1 and 10 mg/kg. However, the high dose resulted in 66% protection while the low dose afforded no protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798797 TI - Stimulation of glomerular epithelial cell growth by doxorubicin. AB - Although doxorubicin nephrosis is commonly used as a model of nephrotic syndrome in the rat, the mechanism of glomerular injury remains unknown. Since a study by others using nonrenal cell lines showed that doxorubicin could increase cell growth at concentrations below the cytotoxic range, experiments were performed to determine whether doxorubicin had similar effects on glomerular cells. At low concentrations (approximately 10(-10) to 10(-7) mol/L), doxorubicin causes a 1.5 fold to three-fold stimulation of primary culture and cloned, passaged glomerular epithelial cell (GEC) growth, as assessed by cell counting, incorporation of tritiated thymidine, and by a fluorescence assay of cell growth. At these concentrations, doxorubicin had no effect on the growth rate of mesangial cells (MCs). Higher doxorubicin concentrations (> 10(-6) mol/L) inhibited the growth of GECs and MCs to a similar degree. Exposure to low concentrations of doxorubicin increased GEC growth under low serum conditions after doxorubicin treatment. Conditions that promoted high rates of GEC proliferation before doxorubicin exposure (pre-exposure to high serum concentrations, or use of subconfluent "stock" cultures) abrogated the growth response to doxorubicin, suggesting that doxorubicin stimulates GEC growth by substituting for growth-promoting factors present in serum. These studies demonstrate that unlike the growth-inhibiting effect of higher concentrations, the growth-promoting effect of low concentrations of doxorubicin is specific for GECs, the glomerular cell population that shows pathologic and functional evidence of injury in doxorubicin nephrosis in vivo. These findings, along with those of others, lead to the hypothesis that at higher concentrations, doxorubicin and other exogenous or endogenous growth-promoting compounds may cause GEC injury by "overstimulation" of the same pathways that promote growth at lower concentrations. PMID- 7798796 TI - Species diversity of 11 beta-hydroxysteroid dehydrogenase in the cardiovascular system. AB - Mineralocorticoid (MC) receptors are found in classic (e.g., kidney) and nonclassic (e.g., heart and aorta) tissues. MC receptor specificity at either site is conferred by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), which metabolizes glucocorticoids to inactive 11-ketosteroids. Because the heart and vasculature may be target tissues for aldosterone, this study was undertaken. Its objectives were to measure 11 beta-HSD at these sites and to compare levels of activity in the atria and ventricles of different species. Toward this end we first determined levels of plasma corticosterone (B) and cortisol (F) (by using radioimmunoassay), in a variety of species, for subsequent correlation with cardiac 11 beta-HSD activity. 11 beta-Dehydrogenation of glucocorticoids was then assayed in ventricles and atria as well as aorta. Tissue homogenates containing 1 to 5 mg protein were incubated for 1 hour in the presence of 1 muCi 5 x 10(-9) mol/L tritiated B or tritiated F and 5 x 10(-4) mol/L oxidized nicotinamide adenine dinucleotide phosphate. Steroid separation and quantitation were achieved by using reverse-phase high-performance liquid chromatography coupled to an online radioisotope detector. For species in which B circulates at relatively high concentrations (rat, rabbit, pig), high levels of dehydrogenation of B to 11-dehydrocorticosterone (A) were observed in both atria and ventricles. Overall, cardiac B to A conversion levels corresponded to between 0.3 and 0.4 pmol A formed/mg protein/hr. 11 beta-HSD activity was also detected in the aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798798 TI - Human liver-derived HEP G2 cells produce functional properdin. AB - Properdin stabilizes the alternative complement pathway C3 convertase and is synthesized by monocytes and myelomonocytic cell lines. Hepatic production of properdin has never been documented, although most other complement components are synthesized by liver. Human liver-derived Hep G2 cells were examined for the ability to produce properdin by using the polymerase chain reaction (PCR). Amplified properdin message was detected by using Southern transfer and hybridization to a murine properdin cDNA probe. Sequencing of the PCR product revealed that the Hep G2 message was nearly identical to the cDNA sequence from U937 cells. Subsequently Hep G2 cultures were stimulated with interleukin (IL-6), 25 micrograms/ml, and culture supernatants were assayed for the presence of properdin by using dot blots. Properdin concentration increased over time, and we found no obvious difference between properdin production by IL-6-stimulated and unstimulated Hep G2 cells. Finally, alternative pathway decay assays confirmed the presence of functionally active properdin in the culture supernatant. Thus, functional properdin is a product of Hep G2 cells, suggesting that biosynthesis of properdin may occur in hepatocytes. Properdin synthesis was not augmented by IL-6, a finding that is consistent with previous observations that properdin is not an acute phase reactant. PMID- 7798801 TI - [A new cause of hereditary thrombophilia: activated protein c resistance]. PMID- 7798799 TI - Aging increases ischemia-reperfusion injury in the isolated, buffer-perfused heart. AB - Survival after acute myocardial infarction is decreased in elderly patients as compared with the overall adult population. Although several cardiac and noncardiac causes could contribute to the increased mortality rate, little is known regarding the relative susceptibility of aging myocardium to injury during ischemia and reperfusion. We hypothesized that the elderly heart is intrinsically more susceptible to damage than the adult heart. The recovery of isolated, buffer perfused rat hearts from elderly animals (Fischer 344 rats, 24 months of age) was compared with that of adult hearts (6 months of age) obtained from the same strain. Hearts underwent 25 minutes of ischemia followed by 30 minutes of reperfusion. Hemodynamic recovery was decreased in elderly (n = 5) as compared with adult (n = 5) hearts, including developed pressure (% of preischemic baseline: elderly 31% +/- 4% vs adult 57% +/- 4%, p < 0.01). Elderly hearts also sustained greater tissue damage, with a markedly increased release of creatine kinase (elderly 2950 +/- 500 U vs adult 860 +/- 345 U, p < 0.01) during the 30 minute reperfusion period. The release of total protein and lactate dehydrogenase, other markers of myocyte injury, was also increased. Thus the elderly rat heart is more susceptible than the adult rat heart to ischemia reperfusion injury. Greater injury during ischemia and reperfusion in an experimental model of aged myocardium raises the possibility of a more rapid progression of ischemic damage in elderly patients suffering acute myocardial infarction. PMID- 7798800 TI - Iron and zinc nutriture of premenopausal women: associations of diet with serum ferritin and plasma zinc disappearance and of serum ferritin with plasma zinc and plasma zinc disappearance. AB - The Second National Health and Nutrition Examination Survey found low iron and zinc intakes and low serum ferritin in many premenopausal women. Therefore food frequency history, serum ferritin, plasma zinc, plasma zinc disappearance, and zinc turnover rate were measured in healthy premenopausal women. Plasma zinc disappearance and turnover rate were determined by inductively coupled plasma mass spectroscopic analysis of the plasma ratio of zinc 67 to zinc 68 before and 30 to 60 minutes after intravenous injection of 67Zn. Food frequency predicted serum ferritin concentration in 38 women and plasma zinc disappearance in 19. Frequent red meat intake was associated with higher serum ferritin concentration and a "normal" plasma zinc disappearance. Frequent milk intake was associated with lower serum ferritin concentration and a rapid plasma zinc disappearance. After exclusion of an outlier, in 18 women serum ferritin concentrations were lower when plasma zinc was < 70 micrograms/dl (p < 0.03), and plasma zinc disappearance and turnover rate were higher when serum ferritin was < 20 ng/ml (p < 0.05). Serum ferritin concentration and plasma zinc disappearance constant were inversely and nonlinearly related (R2 = 0.777, p = 0.0003). These findings suggest that avoidance of red meat increases the risk of iron and zinc deficiencies, and low serum ferritin concentrations suggest the possibility of low zinc nutriture. PMID- 7798802 TI - [Surgical treatment of deep venous reflux. Techniques, indications and results]. AB - INTRODUCTION: complications of deep venous insufficiency can lead to surgery if one fails with medical treatment. The etiology can be primitive or secondary, the symptoms are identical. They go from heaviness of the legs to chronic leg ulcers. Indication and technic of surgery depend on the etiology and the preoperative evaluation. PREOPERATIVE EVALUATION: it has to be anatomical and functional. Invasive investigations as venous blood pressure, ascending and descending venography, and non invasive investigations as duplex or triplex Doppler and plethysmography are used. TECHNICS: one can use three techniques. Valvuloplasty with or without venotomy, and with or without Dacron cuff. Transplantation of an axillary valvulated venous segment to femoral or popliteal vein. Transposition to a valvulated and competent great saphenous vein or deep femoral vein. INDICATIONS: one can propose transplantation or transposition for secondary deep venous insufficiency, and valvuloplasty for primary deep venous insufficiency. Stage 2 or 3 can be a clinical indication for surgery. RESULTS: valvuloplasty has good results with 60 to 80% free of clinical recurrence at 2 years. The results of the other technics seem to be less good. CONCLUSION: the fair results of surgery allow the use of it for some patients with a good evaluation. The improvement of the surgical results lie on the development of paraclinical evaluation and research on venous valvular hemodynamic. PMID- 7798803 TI - [Venous disease in France: an unrecognized public health problem]. AB - Different reasons explain that chronic venous insufficiency remains ill recognized as a public health problem in France: very few epidemiologic studies have been undertaken in this pathology; this disease is very heterogeneous in terms of gravity and clinical evidence: from isolated symptoms to localized clinical signs, with or without severe complications. Clinical semiology is actually not standardised. The analysis of available informations suggests that this pathology represents approximatively 2.6% of the whole health expenditures in France, that is to say an amount of 14.7 billion of Francs for the year 1991. The number of patients suffering from chronic venous insufficiency can be estimated to about 11 millions, whose 7 millions present symptomatic signs (leg heaviness, pain, moderate edema). The number of hospitalizations is around 200,000 per year, of which 63% are in surgery in private clinics. One half of these hospital stays concerned varicose veins (the 8th cause of hospitalization in France). Forty of the patients consulting for chronic venous insufficiency are at work and about 7 to 8% of them get sick leaves for this pathology: around 362,000 sick leaves per year representing 6.4 millions of day lost. On the basis of the medical consumption survey performed by INSEE/CREDES, an extrapolation was made to estimate the different components of costs of chronic venous insufficiency: 41% (drugs), 34% (hospital care) and 13% (medical fees). PMID- 7798804 TI - [Plasminogen activation and erythrocyte aggregation in diabetic patients]. AB - To better understand the abnormalities of red blood cell (RBC) hyperaggregation and elevation of fibrinogen during diabetes mellitus, we have studied the effect of plasminogen activation on RBC aggregation phenomenon. The plasminogen was activated in vitro by adding streptokinase in blood suspensions of 26 diabetic patients and 11 healthy subjects. RBC aggregation measurements were performed by means of the Sefam erythroaggregometer. Results show decreases in either RBC aggregation and fibrinogen level as a result of the plasminogen activation in blood suspensions of healthy subjects. In blood suspensions of diabetic patients, although RBC aggregation and fibrinogen level are decreased following the plasminogen activation, however decreases are less pronounced than those obtained in blood suspensions of healthy subjects. These results mean a decreased degradation of fibrinogen by plasmin in diabetes mellitus and could explain in part the excess of fibrinogen and so the hyperaggregation tendency of red blood cells. PMID- 7798805 TI - [Determination of reference temperatures for a cold test in digital plethysmography]. AB - BACKGROUND: The purpose of this study was to determine optimal warm and cold temperatures for performance of a cold test. METHODS: Thirty-six healthy volunteers (22 women and 14 men; mean age 40, 94 years, range: 20-58) were included in the study. Plethysmographic signal amplitudes were evaluated at different temperatures (47, 45, 43, 40, 35, 20, 15, 13, 11 and 9 degrees C) under standardized conditions, using digital strain-gauge plethysmographic (Perivein Janssen). Reproducibility was assessed by repetition in the same subject of six digital plethysmography signal measurements at 45 degrees C performed at different times and days. Clinical tolerance was estimated according to an analogue scale. RESULTS: Maximal warm amplitude was obtained at 45 degrees C and maximal vasoconstriction at 13 degrees C. The thermal test was well tolerated for the temperature range between 11 and 45 degrees C. Reproducibility of the measurements was satisfactory. CONCLUSIONS: 45 degrees C is the non-nociceptive reproducible vasoparalyzing reference temperature, allowing measurement of maximal digital circulatory capacities. 11 degrees C should be adopted as the optimal vasoconstriction temperature for performance of a cold test. PMID- 7798806 TI - [Experimental simulation of blood flow perturbations induced by the placement of caval filters and thrombi]. AB - Implantation of caval filters to prevent thrombo-embolism is a common medical option for twenty years, since the standard Greenfield model. The numerous new models with various geometries have been the subject of many studies aimed at testing their effectiveness in clot capture and the stability of their fixation to the vein, but very few ones are dedicated to the influence of their shape on blood flow, and to the flow disturbances induced by trapped clots shape and location. So, we have designed a caval blood flow simulation test bench of different filters and clot models. Opcetra and LGM filters were furnished with a reference regular input flow of physiological viscosity fluid. Rigid thrombus model, trapped in filter middle, was a one centimetre diameter sphere; and a recent soft one, which could model itself on the final part of the capture zone, was a two centimetres high cone. Perturbations, eddies, trajectories and velocities were recorded by particles visualization and ultrasound velocimetry. Downstream the Opcetra, velocity vectors were practically axial, no eddies could be seen; the central cylinder had changed the input parabolic flow into a one with two symmetrical maxima. For LGM, on the one hand, from the middle, the sheet branches perturbed the flow and induced several jets. On the other hand, the end ring had created an helicoidal wake which extended up to three centimetres. With thrombi models, for Opcetra, a central spherical clot induced eddies inside the filter, but smoothed the two maxima of the profile, which vanished more rapidly. For the LGM, a central spherical clot increased the perturbations, whereas a final conical one decreased them. Finally, it was clear that filter shape, capture location and clot aspect were the leading causes of the hydrodynamic induced disturbances and might be important for the trapped clots evolution. PMID- 7798807 TI - [Focus on a quick reading of nailfold capillaroscopy]. AB - The diagnostic value of nailfold capillaroscopy was assessed through blind analysis of a continuous series of 307 examinations and a method for quick reading of nailfold capillaroscopy was elaborated with discriminant analysis. The best criteria for predicting the existence of a systemic disease were: major dystrophies (megacapillary, neocapillary and regressive capillary), minor dystrophies and capillary bed abnormalities, especially in patients presenting with vascular disorders of the upper extremities. Capillaroscopic stages and existence of systemic disease were significantly correlated. Discriminant analysis could globally predict the existence of a systemic disease with age and 4 criteria. In subjects with vascular disorders of the upper extremities it needed only age and 3 criterias (abnormal coloration, major dystrophy presence and percentile of minor dystrophies greater than 15%) but without higher diagnostic value (94.2% of patients with systemic disease and 65.6% of patients without systemic disease were correctly classified). Discriminant analysis allows quick reading of nailfold capilloroscopy in the first examination of patients with vascular disorders of the upper extremities. PMID- 7798809 TI - [Why and when to preserve the saphenous veins of varicose patients to serve as an arterial bypass?]. AB - The greater saphenous veins (GSV) are the best substitute for arterial in several locations and are often the only convenient graft. As patients consult for varicose veins at an increasingly younger age and since surgery for varicose veins has become quite popular, there is a risk of unneeded destruction of saphenous veins which will be lacking later. Approximately 80% of the GSV veins in patients consulting for varcosities are normal, slightly dilated or simply have one or more minor areas of dilatation. A special Dacron sheath can be used to maintain these areas of dilatation. The cases presented here demonstrate that these bypass remain patent and that non-sheated areas do not undergo undue dilatation. This technique makes it possible to widen the use of GSV in a larger number of patients with varicose veins. Consequently, it is necessary to verify the caliber of the trunk of GSV during the echo-Doppler examination before treating patients with varicose veins. Suitable GSV should be conserved during initial treatment. Patients should be well informed of the rationale for such decisions, especially concerning the chronological delay between the occurrence of venous varicosities and arterial disease. PMID- 7798808 TI - [History of the treatment of varices]. AB - Diseases of the vein and particularly varicose veins have been recognized since antiquity. The Ebers papyrus, dated 1550 b.c., mentions serpent-shaped dilatation of the lower limbs. The Acropolis tablet of the IVth century b.c. concerning Dr Amynos allows us to visualize an enlarged lower limb clearly showing a varicosity. From 460-377 b.c., Hippocrates noted that a loose tourniquet leads to haemorrhages but that when the tourniquet is tight gangrene ensues and finally that standing up can exaggerate leg ulcerations. Of course much progress has been made since Hippocrates. The school at Alexandria, with Herophilus and Erasistrates speak of vascular ligatures. Their work was unfortunately lost in the fire of the Alexandria library in 391 a.d. Galien himself described varicose vein ligatures in 200 a.d. Leonardo de Vinci's magnificent anatomic studies of veins are widely known. In 1525, Ambroise Pare described leg bandaging for ulcers beginning from the foot up to the knee. In 1585, Fabrice d'Acquapendente described venous valves. In 1676, Wiseman invented the first supportive stockings made of leather and in 1854, Unna described in Vienna the supportive boot which now carries his name. Shortly thereafter new medical and surgical techniques were developed for the treatment of varicose veins. Pravaz, in 1860, invented a syringe which now carries his name and initiated sclerotherapy. At the end of the XIXth century, Trendelenburg performed the first ligatures of the greater saphenous veins. In 1905, and 1906, Keller and Mayo performed the first ablation of the greater saphenous vein and in 1906, Carrel reported the first venous transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798810 TI - [Personalized treatment of varices. Indications in thirty-two cases]. AB - During the 28th Meeting of the College Francais de Pathologie Vasculaire, twelve experts, six angiologists and six surgeons were asked to choose a first intention treatment for 32 case reports of patients with varicose veins based on physical examinations and echo-Doppler findings. The audience made their choice simultaneously by an electronic voting system. In a large number of cases, several therapeutic options were possible. The greater saphenous vein can often be retained in first intention situations with the possibility that several years later the prognosis of the limb may depend on the presence of this vein, particularly in life threatening cases where it is needed for arterial bypass surgery. In some cases it is clear that the greater saphenous vein does not need to be removed and in others, deterioration is clearly sufficient to justify removal. In many cases, the choice between the two options is a decision to be made. Indications depend on the clinical presentation and echo-Doppler findings. The caliber of the greater saphenous vein must be determined for the entire length of the vein. Whenever possible, veins with a diameter below 8 mm should be preserved and the patients should be informed on why the choice was made. Whatever treatment has been chosen, recurrence may be observed and periodic follow-up is required. PMID- 7798811 TI - [Coarctation of the subrenal abdominal aorta revealed by aortic thrombosis]. AB - The authors report the case of a 44 year-old female patient with no particular history who presented with a suddenly occurring severe ischemia of the lower limbs during exercise which revealed a total thrombosis of the subrenal abdominal aorta. Angiography confirmed the diagnosis and demonstrated a partial compensation of the lesion by an important collateral network developed from the parietal and mesenteric arteries. Ultrasonography and computerized tomography showed an extensive coarctation of the abdominal aorta. The main visceral (particularly renal) arterial branches were not involved. The pathologic subrenal aortic segment was surgically resected, and a prosthetic aortobifemoral bypass provided. The further course was marked by several occlusions of the low anastomoses by fibrous hyperplasia. Coarctation of the abdominal aorta is briefly reviewed. This disorder is infrequent, and its infrarenal form can be compatible with a normal life. It can be revealed late, particularly when a thrombotic complication occurs. PMID- 7798812 TI - [Pancreatic-duodenal artery aneurysm ruptured in the digestive tube. Report of a case]. AB - We report the successful treatment of an aneurysm of the pancreatoduodenal artery which ruptured into the duodenum in a 78-year-old patient. The pancreatoduodenal arcades were excluded by aorto-mesenteric bypass and ligature of the gastroduodenal artery. Aneurysm are rarely located in pancreatoduodenal artery. Surgical repair is often difficult due to the close relations with the pancreatic parenchyma. Arteriography is essential to guide the operation. PMID- 7798813 TI - [Importance of complementary peroperative examinations in the treatment of adventitial cystic degeneration of the popliteal artery]. AB - We report a case of cystic adventicial disease of the popliteal artery in a 67 years old man. The realisation of the intra arterial pressure measurements, and the peroperative echography permit to diagnose important associated lesions of the intimal part of the arterial wall. PMID- 7798814 TI - [Multiple intracranial aneurysms in relation to Recklinghausen's disease. Report of a case]. AB - Recklinghausen disease which usually appears by tumors of the nervous system peripheral and central can present anomalies of other systems, particularly vascular anomalies. The damage of renal arteries is well known. Intracerebral aneurysms are rare. Multiple intracerebral aneurysm has been reported in only four cases. We report a case of a patient presenting three intracerebral aneurysms. The patient died of a meningial haemorrhage. This leads us to search for intracerebral aneurysms in Recklinghausen's disease, specially in presence of arterial hypertension. PMID- 7798815 TI - Unit cost analysis in a university hospital: an example from Srinagarind Hospital, Khon Kaen. AB - This is the first analytic study to identify the unit cost in the University Hospital using the standard method of analysis in health economics. The unit costs in the report can be used to calculate the cost of each service for any disease. The costs of the hospital administration cost center and the supportive cost center were both allocated to the patient care service center by the simultaneous allocation method. The cost of teaching personnel was excluded from the analysis because it is quite difficult to estimate and differentiate the ratio of teaching costs to service costs. The hotel cost of the inpatient ward varied from 77.81 baht to 604.7 baht per day. The unit cost per service per day is different from the charge which is presently used at Srinagarind Hospital. Some services, such as in-house transportation are not included in the charge. This study was conducted to identify the unit cost of each service. The decision to establish charges can depend partly on this data and partly on the administrator's judgement. Other factors, such as patient poverty can dictate the final decision. In any case, the hospital and health service center should identify their own unit costs to be able to plan for effective budget management. PMID- 7798816 TI - Observation on the short and long term response to anti-lipemic drugs in southern Thailand. AB - Patients with dyslipidemia were evaluated with regard to the 5 drugs regimen: simvastatin (average dose, 11.8 mg/day), gemfibrozil (dose 963 mg/day), bezafibrate (433 mg/day), fenofibrate (211 mg/day) and acipimox (667 mg/day). The responses to the drug were divided into different time periods and the magnitude of responses were presented either as average changes in per cent from baseline or as proportion of patients (also in %) whose levels changed by a predetermined percentage. These predetermined percentage took into account the variation observed among patients who had more than 3 measurements during baseline. These levels for significant changes were 16 per cent for total cholesterol (TC), 25-30 per cent for high- and low-density lipoprotein (HDL and LDL), and 44 per cent for triglyceride (TG). Our subjects responded to the drugs within the range reported by other investigators except for acipimox which produced no alteration. Sixty to 100 per cent of patients reduced their TC by 16 per cent with an average change in TC of around -16 per cent to -24 per cent. Simvastatin and fenofibrate appeared most effective in altering TC. The HDL increased 10 per cent to 29 per cent depending on the drug but in terms of proportion that responded by an increment greater than 25 per cent, this was seen in only 23 per cent to 45 per cent of the patients. Long term follow-up which was possible only on 42 patients showed 11 who lessened their response and 6 whose response became more marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798817 TI - Risk factors for HIV infection among Thai laborers during 1992-1993. AB - From June 1992 to May 1993, 39,939 Thai men attended the clinic for laborers going abroad at Siriraj Hospital in Bangkok for a pre-assignment physical exam and mandatory blood screen for HIV and syphylis. Of this total, 438 tested positive for HIV antibody (1.1%). Of these, 215 men returned for post test interview and physical exam and were compared with 1,348 men randomly selected HIV-1 seronegative men. None of the HIV-1 seropositive had a history of injecting drug use or had received blood transfusion in the past seven years. HIV-1 seropositivity was associated with the TPHA serological marker for syphylis > 1.160 (p = 0.015, odd ratio 1.8), history of urethritis (p = 0.009, odd ratio 1.92) (Table 4). This study found that HIV-1 seropositive men were mostly single, were likely to be from the rural northern provinces of Thailand or Bangkok. History of purchase of low-fee commercial sex and less condom use were significantly associated with HIV-1 seropositivity as was a history of STD in the year prior to interview. Information on HIV disease and pre-test/post test counselling is needed for Thai laborers who are applying for work abroad to countries which require HIV and syphylis screening. In this effort, the Ministry of Labor and Social Welfare, the Ministry of Public Health and the clinic for laborers going abroad should join forces to provide this service. This will serve to increase awareness and self-determination among an increasingly vulnerable segment of the population who also have the potential to spread HIV infection to their spouse and other sex partners.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798818 TI - Comparison of morphine slow release tablet (MST) and morphine sulphate solution (MSS) in the treatment of cancer pain. AB - A cross-over, single blind trial of MST and MSS in relieving pain of advanced cancer patients is described. Forty-nine cases completed the study. Both MST and MSS gave equally excellent pain relief in the patients as judged by the pain score of VAS and pain rating scale by a nurse, and the duration of sleep. The daily effective dose was 55.5 +/- 19.7 mg for MST and 61.0 +/- 11.0 mg of MSS. PMID- 7798819 TI - Gastric acid secretion in Thai patients with particular reference to the characteristics differentiating types of gastric and duodenal ulcer. AB - Acid secretion in both basal and stimulated states (using augmented histalog test) was studied in 31 normal control patients, 64 duodenal ulcer patients and 101 gastric ulcer patients. Having had the result of acid output study, the 64 DU patients could be classified according to their acid secretion results as 35 DU type I or Normosecretor (54.7%) and 29 DU type II or Hypersecretor (45.3%). For the GU patients which were classified according to the sites of lesions as GU type I (GU above angulus), GU type II (GU associated with DU) and GU type III (GU below the angulus). Their acid output study showed that the GU type I had a rather low BAO and a high MAO close to that of the Normosecretor, but the GU type II and III had their BAO and MAO significantly higher than that of the normal control and close to that of the Hypersecretor. Comparison of acid secretion in this study group to other racial groups showed that the Thai population had acid secretion patterns close to other Asian populations, except that the Chinese in Singapore had a higher proportion of Normosecretor (69.0%) than Hypersecretor (31%). The MAO of the Asian population was found to be lower than that of Europeans. PMID- 7798820 TI - Postoperative elective ventilation in babies with "marked anastomotic tension" after repair of esophageal atresia. AB - The repair of esophageal atresia, preserving the patient's own esophagus is the surgical procedure of choice. In "long-gap" type or in "tension anastomosis" cases, anastomotic complications were known to be higher than in usual cases. From this report, postoperative elective ventilation for 5 days together with neck flexion position reduced such complications with minimal subsequent complications related to the mechanical ventilation. PMID- 7798821 TI - Calcium and phosphate solubility curves for parenteral nutrient solutions containing aminoplasmal-paed, Aminovenos-N-pad or Moripron-F. AB - We investigated the calcium and phosphate compatibility in three amino acid products: Aminoplasmal-paed, Aminovenos-N-pad, Moripron-F. The final TPN sample solution contained 10 per cent dextrose, 1-3 per cent amino acids, 4 mmol/L magnesium sulphate and various combinations of calcium gluconate and dipotassium phosphate. Precipitates and crystallization were inspected visually and microscopically after 24 hrs standing at room temperature. Calcium-phosphate solubility curve were drawn. Among the three amino acid products, Moripron-F gave the highest buffer capacity. These curves are extremely helpful to predict the compatibility of a calcium-phosphate dose in the TPN solution using these three amino acid products. PMID- 7798822 TI - Improvement of inhaler efficacy by home-made spacer. AB - The delivery of aerosol from a metered dose inhaler (MDI) was reported to be more efficient with a spacer. Hence, a home-made spacer modified from a 950 ml low cost plastic bottle, was compared with a MDI and with a 750 ml imported spacer (Nebuhaler). On three consecutive days, at the same time of day, 20 adult patients with chronic asthma inhaled two puffs of terbutaline sulphate (0.5 mg), delivered from MDI alone, MDI with a 750 ml Nebuhlaer and MDI with a home-made spacer. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate. These measurements were carried out immediately before and at 5, 20, 60 min after inhalation of terbutaline. FEV1 was significantly increased (P < 0.05) at 5, 20 and 60 min after administration of terbutaline with MDI via either spacers than with MDI alone but no significant difference was observed between Nebuhaler and the home made spacer. FVC and pulse rate showed no significant change with each method of administration. In conclusion, terbutaline delivered by MDI and home-made spacer was more effective in bronchodilatation than by MDI alone and was just as effective as MDI and Nebuhaler. The home-made spacer therefore offers a simple, inexpensive and more effective method for delivering aerosol drug. PMID- 7798823 TI - Elevation of depressed skull fracture in the neonate by obstetrical vacuum extractor. AB - In this article, three cases of neonatal depressed skull fracture were successfully elevated by means of an obstetrical vacuum extractor. No complications from the procedure were observed. Neonatal depressed skull fractures which are not associated with neurological signs may be safely elevated without surgery by using the obstetrical vacuum extractor. This simple, atraumatic procedure should be considered first for the management of uncomplicated depressed skull fracture in the newborn. PMID- 7798824 TI - A comparative study of coumadin and aspirin for primary cardioembolic stroke and thromboembolic preventions of chronic rheumatic mitral stenosis with atrial fibrillation. AB - The comparative study of the efficacy of coumadin and aspirin in primary cardioembolic stroke prevention of chronic rheumatic heart disease (mitral stenosis) with atrial fibrillation was conducted at Siriraj Hospital, Mahidol University, Bangkok, Thailand. Seventy-nine patients were enrolled in the trial. Allocation of patients into coumadin or aspirin groups depended upon the patients' choice. Nineteen patients were given coumadin at the adjusted dosage to maintain the therapeutic range of International Normalised Ratio between 1.5-3. Sixty patients were given aspirin at the fixed dosage of 75 mg per day. Six patients were lost to follow-up over the 3 yr period; four in the aspirin group and 2 in the coumadin group. There were three patients with nonfatal cardioembolic stroke in the aspirin group but none in the coumadin group after three years of follow-up. Six patients had mitral valve replacement during the study (i.e. three patients in each group). There were complications in 12 patients, 10 in the aspirin (16.6 per cent) and 2 in the coumadin (10.5 per cent) group. The complications in coumadin group were minor bleeding over the thigh in one patient and generalised ecchymosis over the whole body in one other. In the aspirin group, the complication was gastrointestional symptoms, mainly epigastric pain, but no frank bleeding was observed. Primary prevention of cardioembolic stroke in chronic rheumatic heart disease was found to be more effective with coumadin than aspirin. Our study does not support the use of aspirin in primary prevention of cardiac embolism in chronic rheumatic heart disease. PMID- 7798825 TI - "Simplified IVF": program for developing countries. AB - The aim of this study is to assess the results of the "Simplified IVF" program at Ramathibodi Hospital. Ramathibodi IVF program has been in operation since October, 1991. Some steps of the conventional IVF procedures have been modified due to the limitation of resources. The embryo laboratory is a simple, clean room situated in a different building from the oocyte recovery room. Short protocol of GnRHa/HMG is used for ovarian stimulation. Monitoring of the follicular development is performed by ultrasound alone with limited number of scans (2-3 times/cycle). Oocyte retrieval is carried out under transvaginal ultrasound guidance and the aspirate transported to the embryo laboratory in a simple insulated box. Luteal phase is supported by giving micronized progesterone. Eighty five couples have undergone 105 ovarian stimulation cycles. OR was done in 100 cycles from 80 couples. Total oocytes collected is 1091. The fertilization rate is 75 per cent. Embryos were transferred in 97 cycles. Clinical pregnancy occurred in 25 cycles. Pregnancy rate per OR and ET is 25 and 25.8 per cent respectively. Nineteen patients have delivered (6 twins, 13 singletons). Simplification of procedures has enabled the IVF service to be available in a center with limited resources without compromising the results. Other advantages are improvement of the patient's convenience, cost savings and less time consumed as well as being less stressful. PMID- 7798826 TI - Rotational deformity of the distal humerus in cubitus varus. AB - The medial rotation deformity of the distal humerus usually exists in the cubitus varus deformity but has received little attention. Study of this deformity in 29 cases of cubitus varus was carried out using the osteotomized bony specimens that were removed during closed wedge osteotomy in order to determine the actual bone deformity. The average duration of the varus deformity was 5.6 yrs (range 1 to 11). The medial rotation deformity of the distal humerus averaged 27 degrees (range 15 to 45). There was no correlation between the degree of rotation and that of the varus deformity (correlation coefficient r = 0.15). The affected-side shoulder compensated well in both internal and external rotation, and had a greater arc of rotation than that of the normal side. The affected-side shoulder exhibited an internal rotation deformity with an average of 16 degrees (range 5 to 25), with restriction of external rotation of only 13 degrees (range 0 to 20) in comparison to normal side shoulder. PMID- 7798827 TI - The performances of newer free thyroxine assays vs equilibrium dialysis. AB - The performances of 5 different commercial kits for the measurement of serum FT4 concentration; Amerlex-M Free T4 RIA, Gammacoat 125I FT4 2 step RIA, Enzymune test FT4, Amerlite FT4, Berilux FT4 were compared with equilibrium dialysis. All assays demonstrated FT4 values in good correlation with those measured by equilibrium dialysis (r = 0.84-0.89, p < 0.001). The intra-assay coefficients of variation were good and comparable. All methods yielded good separation of uncomplicated hypo/hyperthyroid patients from euthyroid controls. However, only equilibrium dialysis gave consistently normal results of FT4 values throughout pregnancy. All methods other than equilibrium dialysis gave falsely low values in majority of women in the 2nd and 3rd trimester of pregnancy. PMID- 7798828 TI - Comparison study between fasting total serum bile acid and post prandial bile acid in hepatic diseases: a preliminary study. AB - Fasting bile acid, two-hour post prandial bile acid and other liver function tests (Bili, AST, ALT, ALB, Glob, ALP) were measured in 22 normal and 28 liver diseased patients. In normal volunteers, the mean value of fasting total serum bile acid (FTBA) and postprandial serum bile acid (PTBA) were 3.08 mumole/L (S.D. 1.65) range 0.21-6.26 mumol/L, and 8.07 mumole/L (S.D. 2.99) range 4.06-15.65 mumole/L. Comparison between FTBA, PTBA and other liver function tests in various liver diseases from this study the PTBA was not statistically significant superior to FTBA. Therefore, it is not necessary to do the PTBA at this time until more data is available. PMID- 7798829 TI - Five years survival result of twenty-two breast cancers treated by breast conserving therapy at NCI Bangkok. AB - From November 1984 to July 1992 Breast Conserving Therapy (BCT) has been offered to clinical stage 1 & 2 breast cancers. Twenty two breast cancers were treated and passed the five year period. Only one patient was lost in follow-up. The treatment consisted of tumorectomy, full axillary nodal dissection and total breast irradiation with a booster dose at the biopsy site. Adjuvant chemotherapy is administered in cases of positive axillary nodes. There are seventeen living and four deaths. The 5 year survival was 80.95 per cent. The four deaths were node negative and in the young age group (under 36 years of age). Three out of four who died of distant metastasis showed precedent local recurrence. Local recurrence was noted in four patients (19.04%). Second primary breast cancers were found in four patients and two of them died of distant metastasis and one of these two had local recurrence in the first breast carcinoma. There were two survivors from distant metastasis, one with single pulmonary metastasis and another with spine and pelvic bony metastases. Slight to moderate arm edema was found in 5 patients. (22.73%). From our study we have been convinced that BCT seems to give poorer results in terms of survival in the young age group (especially under 36 years of age). Those who are under 36 years of age and have T2 lesion with negative node or local recurrence as well as second primary breast carcinoma should receive adjuvant chemotherapy. PMID- 7798830 TI - Background and mental health status of students who are "well-behaved" in their teacher's perspective. AB - Two hundred and eighty-five students were considered well-behaved, and two hundred thirty-seven students as control group were assessed for their mental health background and mental status. The quality of well-behaved students' parents regarding their ability in bringing up their children was better than that of parents of the control group. Well-behaved students have a higher I.Q. than the control group. They possessed sociable extraversive stable personalities. Regarding their expressions for social acceptance, they needed control people showing them acceptance and wanted to be supervised by others. However, the well-behaved and the students of the control group had no significant signs of difference in expressing love and concern towards oneself. Regarding mental health of the well-behaved, they had normal level of stress and average level of anxiety. The mental health of both groups, for example, stress and anxiety from social-adjustment and being evaluated was not different. Thus, teachers have accurate judgement in distinguishing the well-behaved from the control students. The mental health status of both groups of students was not different. Consequently, the teachers have no worries towards behaviour and mental health status of well-behaved. They can concentrate more on students with problems and behavioural deviations. PMID- 7798831 TI - Routine or selective intraoperative cholangiography. AB - IOC is definitely indicated in patients with clinical indications. It avoided unnecessary exploration of the common bile duct in 32.7 per cent. Of all the clinical indications, palpable common bile duct stone was the most accurate. Dilated common bile duct, dilated cystic duct, elevated serum alkaline phosphatase, multiple small stones and positive imaging investigations were a statistically significant prediction of common bile duct stones. IOC is not justified in patients without clinical indications because of the low incidence of unsuspected common bile duct stone (0.66%) and on the basis of cost effectiveness. The results support the view that IOC is invaluable and should be used selectively. PMID- 7798832 TI - Transabdominal fetal reduction in quadruplet pregnancy during first trimester: a case report. AB - Multifetal pregnancy reduction was performed in a patient with quadruplet pregnancy at the 12th week of gestation. Reduction of the fetuses to two was carried out by injecting potassium chloride solution into the fetal chest under transabdominal ultrasound guidance. No complications were encountered and the woman was delivered of healthy twins at 37 weeks of gestation. PMID- 7798833 TI - The advantages of upper gastrointestinal tract brush cytology. AB - A two-year study of endoscopic brush cytology and biopsy histology was carried out in 63 patients suspected of having malignant lesions in the stomach and the eosophagus. The study was designed to evaluate the accuracy and usefulness of combined cytological examination with biopsy histological examination in the diagnosis of malignancy of the upper gastrointestinal tract. The rate of diagnostic accuracy of the combined technique was found to be high and comparable with those of other published studies. Correlations between the cytological and histological findings were observed in 52 cases (82.53%). The combined method detected malignancy in 27 cases, whereas, the brush cytology alone detected malignancy in 19 cases. The findings of our study indicate that combined brush cytology and biopsy histology under direct vision using fibrescope are of value for the diagnosis of gastroeosophageal malignancy. PMID- 7798834 TI - Epidermolysis bullosa letalis (Herlitz disease): a case report. AB - A case of junctional epidermolysis bullosa was reported. A four-month-old boy was presented with generalised blisters after minor trauma since birth. There was no family history of blistering diseases or consanguinity. Skin examination revealed blisters primarily on the upper and lower extremities. Erosions were also noted on the face, abdomen and buttocks. The lesions healed without milia or scarring formation. Anonychia of all fingers and toe nails were noted. Skin biopsy from the blisters showed subepidermal bulla with a few inflammatory cells. Electron microscopic examination revealed cleavage plane at the lamina lucida and the absence of hemidesmosomes. These findings supported a diagnosis of junctional epidermolysis bullosa. The patient was treated with topical and systemic antibiotics. However, the blisters gradually increased. He died of uncontrolled sepsis and diarrhea. PMID- 7798835 TI - Hepatocellular adenoma in a beta-thalassemic woman having secondary iron overload. AB - An 18-year-old woman had a hepatocellular adenoma of 4 cm across in the right lobe of the liver which was severely hemosiderotic because of beta-thalassemia hemoglobin E disease with numerous blood transfusions. The lesion was an accidental postmortem finding. To our knowledge, this is the second example of liver-cell adenoma occurring in a patient with beta-thalassemia hemoglobin E disease with secondary iron overload. It is suggested that this is an association between hepatocellular adenoma and secondary iron overload of liver cells, a similar event to the relation observed in hepatocellular carcinoma and secondary iron overload of hepatocytes. PMID- 7798836 TI - Echocardiographic features in patients with beta thalassemia/hemoglobin E: a combining effect of anemia and iron load. AB - Hemoglobin concentration, iron parameters and cardiac status of 25 patients with beta thalassemia/hemoglobin E disease were measured. Two-dimensional echocardiography was employed to evaluate chamber size, ejection fraction and muscle fiber shortening. The seventeen patients who had a mean hemoglobin concentration of less than 7.7 g/dl were found to have significantly larger cardiac chambers and higher cardiac output than the patients with higher hemoglobin concentrations. A statistically significant difference in ejection fraction and per cent of fractional shortening of cardiac muscle fibers was not found. A comparison of subjects with ferritin concentrations above and below 1,500 micrograms/L showed no significant difference in chamber sizes, ejection fraction and in per cent fractional shortening. However, a comparison of 14 patients with transferrin saturation > or = 80 per cent with those less than 80 per cent showed a significant decrease in both ejection fraction and fiber fractional shortening in the more highly saturated subjects. By using stepwise multiple regression analysis, the hemoglobin level was shown to significantly determine cardiac enlargement, while ejection fraction and percentage fractional shortening were significantly associated with transferrin-iron saturation. Thus, anemia leads to chamber enlargement, while high transferrin iron saturation is associated with cardiac muscle dysfunction. The findings in the individual patient reflect the integration of these two effects. PMID- 7798837 TI - Hypertension perioperative splenectomy in thalassemic children. AB - We retrospectively studied the intraoperative hemodynamic changes in 100 thalassemic children undergoing general anesthesia for elective splenectomy. They were divided into 2 groups owing to the postoperative hemodynamic response. Eighty-four patients who had an unremarkable postoperative course were group 1, while 16 patients who developed immediate postoperative hypertension were group 2. There were no differences between the groups regarding age, body weight, sex, anesthetic time and operation time, except for the preoperative hematocrits of group 1 patients were slightly but significantly higher. Both groups similarly showed significant increase of the systolic as well as diastolic blood pressure throughout the anesthetic course. The heart rate was significantly increased at the beginning but declined to normal toward the end of the operation. Although none of the patients died postoperatively, all of group 2 patients needed aggressive treatment with diuretic and antihypertensive drugs. Despite the proper management, 3 of 16 patients developed convulsion and one of them had persistent neurological deficit. Since intraoperative and postoperative hypertension which commonly occur in these patients may lead to more serious neurological complications, the authors suggest that careful hemodynamic monitoring must be considered for all thalassemic children undergoing general anesthesia for splenectomy. PMID- 7798838 TI - Effects of pentoxifylline on sperm motility characteristics and motility longevity of postthaw cryopreserved semen using computer-assisted semen analysis (CASA). AB - Computer-assisted sperm movement analysis was used to study the effect of pentoxifylline on human sperm motility characteristics and motility longevity of postthaw cryopreserved semen. This study focused on the following issues: the changes in individual movement characteristics in response to pentoxifylline, the persistence of the response during drug treatment. Computerized analysis was started at 30 min, 3 hrs and 24 hrs, after addition of pentoxifylline. Data obtained showed that pentoxifylline significantly increased percentage of sperm motility, average path velocity (VAP), curvilinear velocity (VCL), straight line velocity (VSL), amplitude of lateral head displacement (ALH) at two of the three time periods (p < 0.05). But, it did not significantly increase linearity (LIN), straightness (STR), and beat cross frequency (BCF) at any time. After 24 hrs, all motility variables were significantly decreased in both groups. However, the 24 hr motility longevity in the treatment group was greater than that of the control group. The present analysis shows interest in the use of pentoxifylline as a sperm movement enhancer for postthaw cryopreserved semen. It shows a beneficial effect in the majority of sperm movement parameters and motility longevity which may increase pregnancy rates after insemination. However, whether this change leads to an increase in fertilizing ability requires further study. PMID- 7798839 TI - Developmental outcome of infants with neonatal polycythemia. AB - The study of the developmental outcome of neonatal polycythemia was performed on 47 polycythemic and 21 controlled infants who were born at the same period of time. It was found that at the age of 1 1/2 to 2 years the number of infants with abnormal DQ was higher in the group of total polycythemic infants (47%) and in the group of asymptomatic polycythemic infants (45%) than that of the control groups (19% and 5.6% of the groups including twin sibs and excluding twin sibs respectively). There was no difference in the developmental test between the symptomatic and asymptomatic patients. In asymptomatic infants the benefit of partial plasma exchange transfusion on developmental outcome was not found and only low birthweight and small for gestational age infants are the risk factors for poor developmental outcome. PMID- 7798840 TI - Significance of an absent or reversed end-diastolic flow velocity in Doppler umbilical artery waveforms. AB - Doppler velocity waveform analysis has been introduced as part of antenatal fetal biophysical assessment. Abnormal waveforms are associated with maternal and fetal complications. The most severe waveform patterns observed, absent end-diastolic velocity (AEDV) and reversed end-diastolic velocity (REDV), are of ominous significance in many cases but the incidence of these waveforms is low and the outcome is varied. The purpose of this study is to assess perinatal outcome in patients showing absent end-diastolic velocity (AEDV) and reversed end-diastolic velocity (REDV) in umbilical artery flow velocity waveforms. We reviewed our experience of patients showing AEDV and REDV in the umbilical artery flow velocity waveforms over nineteen months. Fifteen patients, all in high risk pregnancies, were identified during this period; 9 with AEDV and 6 with REDV. The results were not used in the clinical management. Twelve babies died (3 fetal deaths, 4 stillbirths and 5 neonatal deaths); giving the perinatal mortality is this group as 80 per cent. The interval between the abnormal waveform recording and fetal death or delivery was between 2 hours and 4 weeks. In three fetuses with abnormal diastolic flow, analysis of umbilical vein blood gases revealed severe acidosis and hypoxia. There was also significant perinatal morbidity as judged by low Apgar scores, days in neonatal intensive care, growth retardation and lethal anomalies. These findings suggest that once the diastolic component of umbilical artery flow velocity waveforms become absent or reversed, the fetus is in a state of hypoxia and acidosis and perinatal outcome is catastrophic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798841 TI - Leukocytic count in the diagnosis of acute appendicitis. AB - Two hundred and thirty-three patients with a pathological diagnosis of acute appendicitis from 1989 to 1990 were reviewed. A comparative series of 235 elective cases who were admitted during the same period, was similarly reviewed. Using these data, the binary tables could be constructed and the cutoff point was obtained by plotting the positive and negative predictive values. This series yielded the clinically significant laboratory findings that the cutoff point of total leukocytic count, percentage of neutrophils and total neutrophilic count were 11,500 mm3, 75 per cent and 8,000 mm3 respectively. Combined specificity of all three tests is higher (95.74%), but the sensitivity is lower (61.55%). PMID- 7798842 TI - Malignant Brenner tumor: a case of aggressive clinical course and cutaneous metastases. AB - Malignant Brenner tumor is a very rare ovarian tumor of which the definition of this entity and its biologic behavior remain controversial to this day. In this case report a 30-year-old patient with malignant Brenner tumor was presented with an aggressive clinical course and cutaneous metastases. The disease progressed from apparently unilateral ovarian involvement to intraabdominal, lung and cutaneous metastases. She expired within two months of diagnosis of disease. The histopathology of the ovarian tumor and the metastatic skin lesion are illustrated. In the authors' opinion this case should be categorized as a transitional cell carcinoma of the ovary. PMID- 7798843 TI - Hypouricemia, hypokalemia, proximal and distal tubular acidification defect following administration of outdated tetracycline: a case report. AB - A Thai female patient developed muscular weakness, hypouricemia, hypokalemia and hyperchloremic metabolic acidosis after taking outdated tetracycline. A pathophysiologic study shows a proximal tubular defect for reabsorption of urate and bicarbonate and a distal tubular acidification defect, probably caused by outdated tetracycline. PMID- 7798844 TI - Congenital pseudarthrosis of the tibia: treatment with free vascularized fibular graft. AB - Five children with congenital pseudarthrosis of the tibia were treated by resection of the lesion and reconstruction of the extremity with a free vascularized fibular graft (FVFG). Two of five cases had had multiple surgical procedures before FVFG. These two cases were complicated with the non-union of the proximal grafthost junction. Of these, one case achieved bone union after further resection of the non-union and adding allogenic bone graft and another case denied further operation and was lost to follow-up 6 months postoperatively. Three cases, two of which underwent FVFG as a primary treatment and another one after failure from the Sofield procedure respectively, were initially treated successfully and solid union of the grafthost junctions was within four months postoperatively. Problems including: anterior bowing, refracture, valgus deformity of the ankle and leg length discrepancy occurred in all four followed cases. PMID- 7798845 TI - Detection of various types of human papillomaviruses in premalignant and malignant cervical lesions using DNA-DNA in situ hybridization. AB - Detection of human papillomavirus (HPV) in formalin-fixed paraffin embedded tissue sections by in situ hybridization technique employing biotinylated (HPV) DNA probe 6/11, 16/18 and 31/33/35 was done retrospectively in 25 cases of cervical dysplasia, 32 cases of cervical squamous cell carcinoma in situ, 52 cases of invasive cervical squamous cell carcinoma and 7 cases of adenocarcinoma. HPV could be demonstrated in 10 cases (40.00%) of cervical dysplasia, 8 cases (25.00%) of cervical squamous cell carcinoma in situ and 31 cases (59.61%) of invasive cervical squamous cell carcinoma and 4 cases (57.14%) of adenocarcinoma. Among the dysplastic cases, 4 cases showed HPV 31/33/35, 4 cases showed HPV 16/18 together with HPV 31/33/35, 1 case showed mixed typing of HPV 6/11 and 31/33/35, and 1 case showed mixed typing of HPV 6/11, 16/18 and 31/33/35. In 32 cases of squamous cell carcinoma in situ, 1 case of HPV 6/11; 3 cases of HPV 16/18, 3 cases of HPV 31/33/35 and 1 case of mixed typing of HPV 16/18 and 31/33/35 were present. A case of HPV 6/11, 10 cases of HPV 16/18 and 9 cases of HPV 31/33/35 could be detected among the cases of invasive squamous cell carcinoma. Mixed typing of HPV 6/11 and 16/18; HPV 6/11 and 31/33/35; HPV 16/18 and 31/33/35; HPV 6/11, 16/18 and 31/33/35 were revealed in 2, 1, 3 and 5 cases of invasive squamous cell carcinoma, respectively. In 7 cases of adenocarcinoma, 1, 2 and 1 cases exhibited positivity for HPV 16/18; HPV 6/11 and HPV 16/18; and HPV 16/18 and HPV 31/33/35.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798846 TI - Adrenal function after prednisolone treatment in childhood nephrotic syndrome. AB - Nephrotic syndrome in children is a very common disease in Thailand. Most of the patients respond well to oral prednisolone treatment but side effects of the drug especially adrenal insufficiency remains a threat to all. We studied the adrenal function by studying the response to ACTH stimulation test in 14 Thai children, nine girls and five boys, with idiopathic nephrotic syndrome: immediately, 3, 6 and 9 months after discontinuation of oral prednisolone treatment. Average age on entry to the study was 104.4 months (25-183 months). Prednisolone was given every day for 29 days (6-64 days) then every other day for 542 days (178-1,562 days). Side effects of steroid treatment were gross obesity BMI > 30 (one patient), moderate hypertension (one patient), and marked cushingoid features (two patients). ACTH stimulation tests were normal in 64 per cent of patients within 7 days, 64 per cent at 3 months, 73 per cent at 6 months, and 90 per cent at 9 months after discontinuation of oral prednisolone. We suggest that adrenal insufficiency has to be considered in all children on prolonged prednisolone unit at least 9 months of treatment-free period. PMID- 7798847 TI - Early response of hyperlipidemic subjects to simvastatin. AB - Seventy eight patients with hypercholesterolemia from 4 major hospitals were studied with regard to their responses to an adjustable dose of simvastatin, a HMG-CoA reductase inhibitor. They were followed for up to 6 months with 4 sample points during the drug and 2 prior to therapy. The average dose was 10.2 mg/day (S.D. 5.5). Four were controlled on 5 mg and 4 needed 30 mg per day. Thirty seven per cent had elevated serum transaminases but none to greater than twice normal. Only a third of these showed elevation of transaminases during drug therapy alone. The mean total cholesterol (TC) was 304 mg/100 ml and low density lipoprotein (LDL) was 221 mg/100 ml. These fell 70 and 60 per cent respectively and over 90 per cent of the patients reduced their TC and LDL more than the limits defined from previous long term monitoring of patients (i.e. TC fell by more than 17% and LDL by 25%). High density lipoprotein, HDL, started off at 45 mg/100 ml and rose to an average of 115 per cent. Triglyceride, TG, started off at 207 mg/100 ml and fell to about 86 per cent during simvastatin. However, in terms of the proportion of patients who responded greater than the limit previously determined (i.e. more than a 25% change for HDL and 45% for TG), only about 20 per cent significantly responded with elevation of HDL and 13 per cent dropped their TG. The response of TG was more marked at TG greater than 300 mg/100 ml. PMID- 7798848 TI - A direct radioimmunoassay for free progesterone in saliva. AB - The direct radioimmunoassay using iodinated tracer (125I-HIS-3CMO) has been developed for the determination of salivary progesterone of healthy volunteers with regular menstrual cycles. Lack of significant diurnal variation either in the follicular or luteal phase indicated that collections of saliva could be tailored to the need of individuals making the study somewhat easier. Salivary progesterone has shown to correlate significantly with free serum progesterone reflecting the unbound biologically active progesterone fraction in blood. Moreover, salivary progesterone concentration ranges are similar to those found in other studies. Our findings indicated that determination of progesterone in saliva could be used in place of serum or plasma. Since firstly, it is non invasive, easy for sample collection and a stress-free technique. Secondly, it is much more accurate in prediction of corpus luteum function and ovulation than the basal-body temperature or endometrial biopsy or other clinical predictors currently in use. Finally, determination of daily salivary progesterone levels throughout the menstrual cycle may be advantageously employed as a non-invasive serial sampling technique for the assessment of corpus luteum and ovarian functions. PMID- 7798850 TI - Human corticotropin releasing hormone stimulation test in normal subjects. PMID- 7798849 TI - Mid-trimester abortion using hypertonic saline or prostaglandin E2 gel: an analysis of efficacy and complications. AB - A total of 149 mid-trimester termination of pregnancies using hypertonic saline infusion (125) or prostaglandin E2 gel (24) have been analyzed for efficacy and complications. The mean induction to abortion time (I-A) was 31.7 +/- 9.2 hours in hypertonic saline (HSI) group and 28.4 +/- 27.7 hours in prostaglandin (PGE2) group. Retained placenta occurred in 76 (63.3%) in HSI group and 6 (25%) in PGE2 group. Four (3.3%) in HSI group had pyrexia over 38.5 degrees C and the only one case with proven sepsis developed disseminated intravascular coagulation defect (DIC) which accounted for one case (0.8%) of blood loss of more than 500 ml. There was also one case of mildly disturbed electrolytes in HSI group occurring during the instillation. Minor side-effects of nausea and vomiting occurred in 4 (16.7%) in the PGE2 group only. PMID- 7798851 TI - Intradermal simulated rabies postexposure prophylaxis using purified chick embryo rabies vaccine. AB - The antibody responses of 65 volunteers receiving an i.d. regimen (0.1 ml given at two sites on days 0, 3, 7 and 0.1 ml given at one site on days 30 and 90) were compared with the control group of 35 volunteers receiving the standard i.m. regimen. By day 14, seroconversion was observed in all vaccinees in both groups. Geometric Mean Titers remained higher than 0.5 IU/ml throughout the study period. At the end of the observation period on day 365, antibodies persisted in all subjects. The multisite i.d. PCEC regimen has been proved as immunogenic as the standard i.m. regimen. Both regimens were well tolerated. Thus, it would be the effective and cheapest available rabies post-exposure treatment using tissue culture vaccine. PMID- 7798852 TI - Management of cobra bite by artificial respiration and supportive therapy. AB - During the period when the hospital ran out of cobra antivenom, 4 patients bitten by cobra with neuromuscular symptoms and respiratory depression were treated with artificial respiration. Complete recovery was noted within 36 to 72 hours. The data are interpreted to indicate the reversible binding of the venom to receptors. Artificial ventilation appears to be another alternative to specific antivenom treatment and may be used when the antivenom is not available or if there is antivenom hypersensitivity. PMID- 7798853 TI - Splenic cystic lymphangiomatosis: an unusual cause of massive splenomegaly: report of a case. AB - A 29-year-old woman had a history of an upper quadrant abdominal mass for about 6 years. An ultrasound examination revealed splenomegaly containing several cysts. On exploratory laparotomy, multiple cysts were found in the spleen. Because of the extensive involvement of the spleen, splenic salvage could not be performed, and total splenectomy was done. Both morphological and histological features of the removed spleen were typical of cystic lymphangiomatosis. PMID- 7798854 TI - America's most important specialty. PMID- 7798855 TI - The family in family medicine revisited, again. PMID- 7798856 TI - Levels of physician involvement with patients and their families. A model for teaching and research. AB - BACKGROUND: We present an educational model that describes physician skills for addressing psychosocial concerns of patients, ranging from basic medical questions to in-depth psychotherapy. This model improves upon previously published models by integrating into one hierarchy levels of physician involvement with individual patients and levels of involvement with families. METHODS: Ten faculty family physicians were videotaped during 200 office visits. Interviews were categorized according to the model, with a 79% interrater agreement. RESULTS: Most visits involved the lower three levels of physician involvement (41%, level 1; 35.5%, level 2; and 23%, level 3). Discussion of family context occurred in a majority (58.5%) of visits, primarily when another family member was in the room and during preventive care visits. Higher levels were associated with longer visits--about 3 minutes more for each additional level. CONCLUSIONS: This investigation suggests that the levels of physician involvement model can be reliably measured. This model may be a useful tool for education and research, particularly the study of physician interview skills appropriate to family medicine. PMID- 7798857 TI - Referrals for alternative therapies. AB - BACKGROUND: The purpose of this study was to examine how allopathic physicians participate in the decision to refer patients for alternative therapies. METHODS: A pretested, self-administered, structured questionnaire was distributed simultaneously to all area physicians at community locations in Washington State, New Mexico, and southern Israel. The primary outcome measures were monthly and yearly rates of referral to alternative therapies. RESULTS: More than 60% of all physicians made referrals to alternative providers at least once in the preceding year and 38% in the preceding month. Referrals were generally based on patient requests, synergy between the alternative therapy and the patients' cultural beliefs, failure of conventional treatment, and the belief that patients have "nonorganic" or "psychological" disease. There was no relationship between the rate of referral and the referring physician's level of knowledge about, beliefs about the effectiveness of, or familiarity with alternative therapies. CONCLUSIONS: Primary care physicians are more likely than other medical specialists to be knowledgeable about, personally subscribe to, and refer patients for alternative therapies. Physicians who use alternative techniques for themselves and their families or who adopt complementary therapies into their practices have higher rates of referrals. Referral rates and patterns were similar between sites despite considerable cross-cultural and health system differences. Given the high rate of referral and the absence of an apparent internal logic for such recommendations, guidelines and physician education may be advisable. PMID- 7798858 TI - Pain and cramping associated with cryosurgery. AB - BACKGROUND: Many different cryosurgery methods have been described for the treatment of cervical intraepithelial neoplasia (CIN). The purpose of this study was to evaluate the pain and cramping perceived by patients undergoing four specific cryosurgical methods. METHODS: Seventy women consented to the prospective trial and were assigned to one of four cryosurgery techniques: a 2 minute double freeze, a 3-minute double freeze, a 5-minute single freeze, and a 5 minute double freeze. Immediately following the procedure, a trained interviewer recorded each woman's perceptions of pain and cramping. Age, parity, marital status, financial class, race or ethnicity, lesion severity, and pretreatment with a nonsteroidal anti-inflammatory drug (NSAID) were included in the analysis. RESULTS: The median pain scores for the 2-minute double freeze, the 3-minute double freeze, the 5-minute single freeze, and the 5-minute double freeze were 4, 3, 3, and 7, respectively, on a scale of 0 to 10. The median cramping scores for the procedures were 0, 0, 0, and 7, respectively. The median pain and cramping scores were significantly higher for the 5-minute double freeze than for any of the other procedures (P = .012 and P = < .001, respectively). CONCLUSIONS: Pain and cramping are associated with cryosurgery, but the 5-minute double freeze caused the most pain and cramping of all the cryosurgery methods tested. Pretreatment with an NSAID did not lessen the cramping or pain perceived during the 5-minute double freeze. PMID- 7798860 TI - Patient attitudes regarding physician inquiry into spiritual and religious issues. AB - BACKGROUND: Most physicians do not address spiritual and religious issues with patients, although there are data documenting the relationship between religious variables and disease, health, and well-being. The purpose of this study was twofold: to examine patient attitudes regarding physician-directed inquiry about issues related to spiritual matters and faith; and to identify screening variables that would identify patients who would be receptive to such a discussion. METHODS: A Spiritual and Religious Inquiry (SRI) questionnaire was administered to patients presenting for care in a family practice center. RESULTS: Patients' frequency of religious service attendance (at least monthly) predicted their acceptance of physician inquiry into their religion and personal faith (P < .01) and acceptance of physician referral to pastoral professionals for spiritual problems (P < .01). CONCLUSIONS: This study supports the use of frequency of religious service attendance as a screening variable for patients receptive to physician-directed inquiry into religious and spiritual issues. It also confirms that patients are accepting of physicians' referring patients to pastoral professionals (ie, clergy) for spiritual problems. PMID- 7798859 TI - Comparison of home glucose monitoring with the oral glucose tolerance test to detect gestational glucose intolerance. AB - BACKGROUND: Recent evidence suggests that infant morbidity is increased among women who have abnormal prenatal glucose screening tests but who do not have gestational diabetes mellitus (GDM). These women fall into a diagnostic gray zone and historically have not been treated. METHODS: Forty-eight pregnant women with abnormal oral glucose challenge test results performed self-monitored blood glucose (SMBG) testing seven times per day for 1 week before undergoing a diagnostic 100-g oral glucose tolerance test (OGTT). At delivery, perinatal complications and birthweights were recorded. Results of SMBG tests for women with normal OGTTs were correlated with infant birthweights. RESULTS: Thirteen infants (37%) were found to be large for gestational age (LGA). Significant correlation was found between increasing birthweight and increasing average fasting SMBG values (P < .001), increasing percentage of SMBG values above 120 mg/dL (6.7 mmol/L) (P < .01), and increasing average SMBG values (P < .016). CONCLUSIONS: Maternal home glucose values at 28 weeks correlate with the risk of LGA infant births among women in the diagnostic gray zone. Women with average fasting SMBG values > 95 mg/dL (5.3 mmol/L) are at increased risk for giving birth to LGA infants and may be more likely to exhibit complications usually associated with GDM. PMID- 7798861 TI - A multivariate model for specialty preference by medical students. AB - BACKGROUND: Numerous studies have demonstrated differences among students regarding their preference of a medical specialty. The goal of the present research was to develop a model for the selection of a primary care specialty (ie, family practice, general internal medicine, medicine/pediatrics, and general pediatrics). METHODS: A self-administered questionnaire was mailed to 822 first year through fourth-year medical students at the University of Michigan Medical School in Ann Arbor. Students listed their first preference for medical specialty, anticipated income and work hours, and the influence of attitudinal and social factors on their preference. A total of 645 (78.5%) students responded. Average age was 25; 58% were male, and 77% resided in Michigan. RESULTS: Overall, 34.3% of the medical students who responded to the questionnaire expressed a preference for a surgical specialty; 27.3%, primary care; 19.9%, a hospital-based practice; and 18.5%, nonprimary care and non hospital based practice. A multiple logistic regression model developed on preference for a primary care specialty achieved a classification accuracy of 82%. The most important factors influencing specialty preference were sex, expected income, attitudes about general medicine issues, attitudes about surgery, and the influence of other people. CONCLUSIONS: No single factor dominates a student's preference for primary care. Students preferring primary care were most strongly influenced by their perceptions of practice variations. Students preferring nonprimary care specialties were more interested in income, prestige, and hospital-based practice. Medical school faculty had no significant impact on the preferences of either group of students. PMID- 7798862 TI - Vas deferens occlusion during no-scalpel vasectomy. AB - The increasing popularity of the no-scalpel vasectomy (NSV) technique in the United States is driven by patient demand for surgical procedures presumed to be less invasive and by the somewhat lower complication rate of the NSV technique. The NSV technique addresses vasal delivery but not vasal occlusion. Intraluminal red-hot wire cautery with sheath closure over the inguinal end of the cut vas (Schmidt's method) has the lowest failure rate of all reasonable vas occlusion methods. The anatomical relationships of scrotal layers can be unclear during the NSV technique. Accurate identification of the sheath layer is critical to sheath interruption if this method of occlusion is to be used. Placement of an absorbable purse-string suture for sheath interruption during the NSV procedure is described. Special attention must be given to placement of one suture bite in the deep (posterior) sheath wall. The vasal occlusion technique described in this paper blends a refined method of vasal delivery (NSV) with the most effective method of vasal occlusion (cautery with sheath interruption). PMID- 7798863 TI - Neurocysticercosis: an old disease with new questions. AB - Cysticercosis is a parasitic infection of the central nervous system that occurs in some geographic regions and is transmitted through contaminated food or by the fecal-oral route. Treatment depends on the degree of central nervous system involvement. Ventricular cysts require surgery. Parenchymal involvement requires systemic antiparasitic therapy. Computed tomography and magnetic resonance imaging are used to image patients with neurocysticercosis. Magnetic resonance imaging is more sensitive for cerebral involvement than in computed tomography. Computed tomography is more sensitive to calcifications than is magnetic resonance imaging. PMID- 7798864 TI - Suspected trimethoprim/sulfamethoxazole-induced hypoprothrombinemia. AB - The following report illustrates a case of trimethoprim/sulfamethoxazole-induced hypoprothrombinemia in a patient receiving ongoing warfarin therapy for atrial fibrillation and aortic valve replacement. He was treated with trimethoprim/sulfamethoxazole (TMP/SMX) for sinusitis. During this time, the patient's prothrombin time international normalized ratio (INR) increased 3.5 times higher than the baseline value. The INR values decreased when the antibiotic was discontinued. If a patient is on warfarin and TMP/SMX is added, INR values should be monitored closely. PMID- 7798865 TI - Predicting large-for-gestational-age infants. PMID- 7798866 TI - Guidelines for managing ankle injuries: the Ottawa ankle rules. PMID- 7798867 TI - Taking the gravel. PMID- 7798868 TI - Study of the regenerating newt retina by electrophysiology and immunohistochemistry (bipolar- and cone-specific antigen localization). AB - Immunohistochemical and electrophysiological examinations were carried out to investigate the sequence of appearance of the retinal neurons during regeneration after a complete surgical removal of the original retina of the newt. We produced a monoclonal antibody, RB-1, specific for cone photoreceptors and a subtype of bipolar cells in adult newt retina. This antibody was used as a major tool for this analysis. Appearance of spiking activity as a possible marker of ganglion cell differentiation was examined with whole-cell patch-clamp techniques. Spiking cells, which possessed voltage-dependent Na+, K+, and Ca2+ channels similar to those of mature ganglion cells, appeared in the regenerating retina by 24 days before cone photoreceptors had been labeled by the RB-1 antibody. Cones and ganglion cells differentiated before the retina had been segregated into distinct synaptic layers. The RB-1-labeled bipolar cells as well as PKC-immunoreactive bipolar cells appeared in the regenerating retina after the segregation of the synaptic layers. Their appearance seemed to coincide with the appearance of immunoreactive amacrine cells described previously (Negishi et al. [1992] Dev. Brain Res. 68:255-264). During embryonic development of the newt retina, cone photoreceptors appeared prior to bipolar cells. Thus the process of reformation of a functional retina seems to follow the same steps as differentiation of retina during development. PMID- 7798869 TI - Ontogeny of cardiac function in the brine shrimp Artemia franciscana Kellogg 1906 (Branchiopoda: Anostraca). AB - In newly hatched brine shrimp (Artemia franciscana) cardiac organogenesis and function could only take place with the onset of segmentation. Consequently differences in age, body size and temperature (in the range 22-34 degrees C) affected the ontogeny of cardiac activity only indirectly, through their influence on developmental stage. Once present the frequency of cardiac activity (heart beat) increased with increasing body size and concomitant differentiation of cardiac tissue. At least initially, (dry body weight 11-16 micrograms) heart rate was independent of temperature and weight specific heart rate was independent of body size. When differentiation neared completion, and cardiac growth switched to elongation (dry body weight > 16 micrograms), there was a change in the pattern of cardiac function. There was now a decrease in heart beat with increasing body size and weight specific heart rate showed an inverse relationship with body weight. Heart rate also became temperature dependent, although it remained relatively insensitive. In conclusion it is suggested that the ontogeny of cardiac function in Artemia is constrained by an anamorphic (direct) pattern of development where segment formation occurs post hatch. Early cardiac functioning cannot be predicted on an allometric basis, as cardiovascular structure and function changes qualitatively during ontogeny. PMID- 7798870 TI - Fraud and abuse revisited. Current schemes and scams in Florida. PMID- 7798871 TI - Neurosurgical malpractice insurance survey. Florida 1993. AB - A survey of Florida neurosurgeons was conducted in April 1993 with a 68% response rate. One hundred twenty-three (81%) had malpractice insurance. Of the 29 (19%) without insurance, all but one practiced in South Florida. Cost was the major factor in dropping coverage. The cutoff appeared to be in excess of $100,000 per year for coverage for $250,000 per incident. Over 50% have considered early retirement. Those without coverage are limiting patient access. The number unable to afford minimal coverage is likely to increase; consequently patient access will continue to decline unless reforms allow coverage at a reasonable cost. PMID- 7798872 TI - Non 0-1 Vibrio cholerae septicemia and culture negative neutrocytic ascites in a patient with chronic liver disease. AB - Non 0-1 Vibrio cholerae infection is often associated with ingestion of contaminated seafood and its common presentation is gastroenteritis. Septicemia may be found in immunocompromised hosts resulting in mortality approaching 50%. A case is reported of non 0-1 Vibrio cholerae infection presenting with septicemia in a patient with neutrocytic ascites suggestive of spontaneous bacterial peritonitis. PMID- 7798874 TI - Workers' compensation course required. PMID- 7798873 TI - The time has come to lift the economic embargo against Cuba. AB - The United States embargo against Cuba, which makes trade illegal, contributes to that country's death and disease. The policy is obsolete, counterproductive and should be changed to bring peace between the two nations and help restore the health of the Cuban people. Along with the ban on trade is the ban on traveling. The United States' controls contradict the most fundamental values upon which this country stands. Despite current restrictions, physicians can travel to Cuba and they should in order to observe the island's system for themselves. PMID- 7798875 TI - Recent advances in neural transplantation. Relevance to neurodegenerative disorders. AB - Anatomical and behavioral characterizations of neural transplants, whether within (allograft) or across (xenograft) species, have provided evidence that the transplant survives, integrates with the host tissue, and may lead to functional recovery. Several animal models of neurodegenerative disorders demonstrate the feasibility of using neural transplantation as an alternative treatment for these human diseases. While more elaborate basic animal studies are needed, clinical trials have begun. Neural transplantation is currently used as an experimental treatment for Parkinson's disease and several investigators have suggested using the same treatment procedure for other neurodegenerative disorders, such as Huntington's and Alzheimer's disease. PMID- 7798876 TI - Domestic violence. PMID- 7798877 TI - A cup of hemlock. PMID- 7798878 TI - Other side of the controversy. PMID- 7798879 TI - HTLV-I/II infection in a high viral endemic area of Zaire, Central Africa: comparative evaluation of serology, PCR, and significance of indeterminate western blot pattern. AB - The frequency of indeterminate Western blot (WB) seroreactivities against HTLV-I "gag encoded proteins" only, and the use of low specific diagnostic WB criteria led to the overestimation of HTLV-I seroprevalence in initial studies in intertropical Africa and Papua New Guinea. In order to clarify the meaning of such seroreactivity, 98 blood samples of individuals from a high HTLV-I endemic area in Zaire, Central Africa were studied by a WB assay containing HTLV-I disrupted virions enriched with a gp 21 recombinant protein and a synthetic peptide from the gp 46 region (MTA-1), and by the polymerase chain reaction (PCR) with 3 primers pairs and 4 different HTLV-I and or HTLV-II-specific probes. These 98 samples were taken mainly from patients with neurological diseases and from their relatives. Using stringent WB criteria, 28 sera (29%) were considered as HTLV-I-positive, 3 as negative and 67 (68%) as indeterminate. A large proportion of these indeterminate sera would have been considered as HTLV-I-positive samples according to previous low specific WB diagnostic criteria. After PCR, 35 samples (36%) were considered as positive for the presence of HTLV-I proviral DNA. Out of the 67 WB seroindeterminate, 10 (15%) were found HTLV-I-positive by PCR. These 10 individuals exhibited in WB multiple band reactivity with p19 and/or p24 (7 cases of both) associated in 6 cases with rgp 21, but never with MTA-1. No samples were found PCR-positive for HTLV-II despite the findings of 11 sera suggestive of HTLV II by WB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798881 TI - Atypical strain of hepatitis E virus (HEV) from north India. AB - Hepatitis E virus (HEV) infection was detected during an epidemic in North India. Virus particles present in the stool of an acutely ill patient (YAM-67) was transmitted intravenously into rhesus monkeys (M. mulata) and orally to a human volunteer. Virus-like particles (VLPs) of 32-34 nm were detected in the bile of monkeys and in the stools of the human volunteer by means of solid phase immune electron microscopy (SPIEM) with acute homologous and heterologous sera. The VLPs were confirmed to be HEV by a reverse transcription polymerase chain reaction (RT PCR). Virus-like particles from human volunteer stools were passaged further into rhesus monkeys. A bimodal rise in aminotransferase levels were observed in the animals, and liver histopathology indicated mild to severe form of hepatitis. Further, SPIEM and RT-PCR analysis in monkey bile revealed presence of virus from 15 to 45 days post-inoculation. Rechallenge of the animals 6 months after recovery with the same viral inoculum failed to produce abnormal liver function tests indicating the presence of protective immunity during this period. The VLPs in the stool from the patient (YAM-67) with epidemic hepatitis were found to retain infectivity even after several cycles of freeze-thawing and exposure at 37 degrees C for 2 days. Moreover, these VLPs from the patient, human volunteer, and monkeys did not react with an anti-HEV chimpanzee serum from NIH, Bethesda, MD. These findings indicate that this North India isolate of HEV is an atypical strain of HEV. The present study further validates that the rhesus monkey is a suitable experimental model for HEV. PMID- 7798880 TI - Novel application of a point mutation assay: evidence for transmission of hepatitis B viruses with precore mutations and their detection in infants with fulminant hepatitis B. AB - Mutations of the precore region of hepatitis B virus (HBV) genome have been associated with fulminant and severe chronic hepatitis. However uncertainty remains about the clinical significance and transmissibility of these mutant strains. A point mutation assay (PMA) was developed to identify qualitatively and quantitatively mutations affecting precore amino acids 1 and 28. We have analysed serum samples from six mother-infant pairs where perinatal transmission of HBV has occurred and where the mothers were HBV carriers without detectable serum HBeAg. In three cases fulminant hepatitis developed in the infant, in two cases acute hepatitis resolved, and in one case the infant was immunised and did not become infected. We also examined serum from a healthcare worker, an anti-HBe seropositive HBV carrier, believed to have transmitted HBV infection to a patient. The PMA results were confirmed in all cases by direct sequencing of polymerase chain reaction (PCR) products using nested and double-nested PCR with primers to the precore and X region. Precore aa28 mutant-type virus was detected in the serum of one mother at the time of delivery of three of her children, two of whom developed fulminant hepatitis. Another mother of an infant with fulminant hepatitis had no precore mutations. In one mother-infant pair a mixed viral population was found; the acute hepatitis B in the infant resolved. The HBV sequence from the healthcare worker was also of aa28 mutant type. No mutations of aa1 were detected in any of the specimens. The study supports the association of precore mutations with some cases of transmission of HBV infection from HBeAg negative mothers to their infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798882 TI - Elevated rubella antibodies in patients with chronic liver disease. AB - Patients with autoimmune chronic active hepatitis (AICAH) and certain other chronic liver disorders often have very high titres of haemagglutination inhibition (HI) antibodies to rubella virus. In this study it is shown, using floatation centrifugation, that the high rubella HI reactivity is not caused by nonspecific lipoprotein inhibitors but rather by antibodies specific for the rubella haemagglutinin (E1 glycoprotein). After sucrose density gradient ultracentrifugation of sera the major HI reactivity was recovered in the IgG containing fractions. The IgG antibody fraction was strongly reactive by an indirect enzyme-linked immunosorbent assay (ELISA). Higher prevalence and titres of rubella antibodies were also demonstrated by the complement fixation (CF) test using a haemagglutinin-free antigen, and by an indirect haemagglutination (IHA) test (Rubacell) using a cell-associated antigen which is distinct from the antigens used in the HI and CF tests. This high rubella antibody response is therefore demonstrated using three distinct antigen-antibody systems. By means of absorption experiments and radioimmunoprecipitation assays the coating antigen used in the IHA test was shown to reside in the E2 glycoprotein. The cause of this enhanced antibody response to rubella virus structural proteins remains elusive. PMID- 7798883 TI - Humoral immune responses and cytomegalovirus excretion in children with asymptomatic infection. AB - Forty-two seropositive children aged 3 to 5 years attending a kindergarten were followed up for 1 year in order to examine the relationship between humoral immunity and cytomegalovirus (CMV) excretion status. Anti-CMV antibodies were measured at the beginning and end of the study by enzyme-linked immunosorbent assay, neutralizing antibody test, and immunoblot techniques. Among these children, 32 persistently shed virus in urine, 2 intermittently shed CMV, and 4 experienced reactivation during the study. Virus was never isolated from 4 seropositive children. The level of anti-CMV IgG antibody in seropositive children who remained nonshedders was significantly higher than in children who shed virus during follow-up. On immunoblots, all seropositive nonshedders reacted to a CMV-specific 65 kD antigen, whereas most shedders (80%) did not. These findings suggest that humoral immunity plays a role in controlling persistent CMV infection in children with asymptomatic infection. However, the humoral immunity measured by the neutralizing test and the presence of antibodies against CMV specific envelope antigens (116 kD/55 kD) apparently play a limited role in modifying persistent excretion and regulating reactivation of latent CMV. Immune evasion by CMV to block these antigens may explain these results. PMID- 7798884 TI - Hepatitis C virus infections in transplant patients: serological and virological investigations. AB - Hepatitis C virus (HCV) is transmitted by organs of HCV antibody-positive donors to transplant recipients. This study investigated the serological and virological responses of 14 initially HCV antibody-negative transplant patients who received organs from four HCV antibody-positive donors (A-D) (before donor screening for HCV infection was introduced in 1991). Second generation HCV enzyme immunoassay (Abbott HCV EIA) was used to detect anti-HCV antibody. Recombinant immunoblot (RIBA-2; Chiron Corporation) and Wellcozyme Western blot (Wwb) assays were compared as confirmatory assays of positive EIA results. Reverse transcription (RT) followed by "nested" polymerase chain reaction (PCR) was performed to detect viral RNA. HCV RNA was only found in the sera of donors B and C, however, transplantation of organs from all donors resulted in infection of all recipients. HCV RNA was found in recipient sera within 30 days after transplant and remained detectable throughout the period of sampling. An anti-HCV antibody response was found in only 6 (of the 14) recipients and only after 300 days. Much longer periods passed before detection of HCV antibody in six recipients. For detection of HCV infection in transplant recipients it is essential that testing for HCV RNA by RT-PCR is carried out. PMID- 7798885 TI - Hepatitis C virus antibody prevalence among human immunodeficiency virus-1 infected individuals: analysis with different test systems. AB - Sera of 383 human immunodeficiency virus (HIV)-1-infected individuals from Frankfurt (Main)/Germany were assayed by two hepatitis C virus (HCV) screening tests (Abbott second generation, Ortho second generation). This population showed a prevalence for reactivity with both tests of 20.8% (80/383). Examination of all reactive sera (91/383) by a supplemental assay (Chiron RIBA 2) gave for 46 sera a positive, for 33 sera an indeterminate, and for 12 sera a negative result. Further analysis focussed on these RIBA 2-indeterminate and -negative samples. Analysis of the sera using an in-house Western blot with three different Escherichia coli-expressed HCV proteins revealed that none of the RIBA 2 negative, but 24 of the 33 RIBA 2-indeterminate sera, including 3 of 4 c33c (NS3) reactive samples, were reactive with a recombinant core protein. Twenty-one of 22 c22-3 (core) indeterminates stained the core antigen in the in-house Western blot and 3 of them in addition a NS5 moiety. HCV-polymerase chain reaction (PCR) was positive for 14 of the 24 RIBA 2-indeterminate sera, but for none of the RIBA 2 negative or Western blot nonreactive samples. Discrepant results between the two screening tests could not be explained by differences in the antigen compositions (i.e., a NS3-NS4 moiety of 111 amino acids present in the Ortho enzyme-linked immunosorbent assay (ELISA), not present in the Abbott or RIBA 2 assays). PMID- 7798886 TI - Case report: psychosis associated with hepatitis B. AB - An acute disintegrative disorder in a child with acute hepatitis B virus (HBV) infection is described. Both hepatitis B surface antigen (HBsAg) and HBV-DNA were detected in cerebrospinal fluid (CSF) by means of enzyme-linked immunosorbent assay (ELISA) and the polymerase chain reaction (PCR) technique respectively. A markedly elevated level of CSF adenylate kinase (AK), which normalised as the patient recovered spontaneously, suggested an organic brain disorder. Demonstration of intra-blood-brain barrier production of IgG supported the possibility of local infection by HBV within the central nervous system. PMID- 7798887 TI - Rapid detection of virus genome from imported dengue fever and dengue hemorrhagic fever patients by direct polymerase chain reaction. AB - Serum specimens from patients with imported dengue fever and dengue hemorrhagic fever were directly subjected to reverse transcription and polymerase chain reaction (RT-PCR) without any RNA purification. The amplified virus genome was detected within 3 hours. The results of PCR corresponded closely to the results of virus isolation using cultured mosquito cells, suggesting that direct RT-PCR procedure greatly facilitates rapid diagnosis of dengue infection. PMID- 7798888 TI - RB tumor suppressor gene expression in hepatocellular carcinomas from patients infected with the hepatitis B virus. AB - Hepatitis B virus (HBV) infection is closely associated with the development of hepatocellular carcinoma (HCC), but definite mechanisms by which it could play an etiologic role have not yet been identified. Modifications of the function of the RB tumor suppressor gene, which regulates the cell cycle, could provide such a mechanism. In the present study, the expression of the protein product of RB, pRB, was evaluated by immunohistochemical staining in HCC tissues from 25 patients from China and the United States, adjacent nontumorous liver from 19 of those patients, five human HCC cell lines, three human hepatoblastoma cell lines, and five specimens of normal human liver. Representative samples were also evaluated by western blot. Altered expression of RB was detected in eight HCC tissues (pRB undetectable in five HCCs and detected in < 1% of nuclei of HCC cells in three others); all eight had detectable hepatitis B surface or core antigen in the adjacent nontumorous liver, indicating active HBV infection. pRB was detected in 10-95% of nuclei (normal expression) in the remaining 17 HCCs, and in many nuclei in all 19 nontumorous livers, and in the 5 normal livers. No pRB staining was detected in the nuclei of three HCC cell lines, but pRB was detected in > 90% of nuclei of the other HCC and hepatoblastoma cell lines. The relationship of pRB expression to mutations of the p53 tumor suppressor gene was also examined. The absence of detectable nuclear pRB by immunohistochemical staining was associated with the presence of presumed mutant p53 detected by immunohistochemical staining in four out of five HCC cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798889 TI - Genotype distribution of hepatitis C virus infection in Taiwan. AB - To investigate the prevalence of genotype distribution of hepatitis C virus (HCV) infection in Taiwan, genotypes were identified in 122 (36 anti-HCV-positive blood donors, 44 anti-HCV-positive aborigines, 28 hemodialysis patients, and 14 patients with chronic liver diseases) of 280 subjects, using polymerase chain reaction by Okamoto's type-specific primer method. Type II was the dominant (66.7%) type among anti-HCV-positive blood donors, followed by type III and type IV with the same percentages (16.7%), while none of type I was detected. The prevalence of genotype distribution were 75.0%, 81.1%, and 64.3% for type II, 4.6%, 17.9%, and 21.4% for type III, 13.6%, 0%, and 7.1% for type IV, for the aborigines, hemodialysis, and chronic liver diseases groups, respectively. Four subjects revealed mixed infections by two different genotypes: two cases of II and III; and each one case of II and IV, and III and IV. Diverse genotype distributions in two hemodialysis groups disclose the existence of obvious regional differences even within a region. The results reveal the highest prevalence of type II as in Japan. However, there is a higher prevalence rate of type IV than in Japan. PMID- 7798890 TI - Detection of respiratory syncytial virus by RNA-polymerase chain reaction and differentiation of subgroups with oligonucleotide probes. AB - The polymerase chain reaction (RNA-PCR) was used for specific detection of respiratory syncytial virus (RSV) genomes in clinical specimens. A set of primers was selected from conserved regions of the 1B and N genes for detection of both subgroups. The primers were found to be RSV specific, all RSV strains generated a 218 bp product, and no RSV specific amplified product was obtained when nucleic acids from a variety of micro-organisms from the respiratory tract were subjected to the RNA-PCR. We took advantage of the sequence heterogeneity of the amplified products to discriminate between the A and B strains by hybridisation with subgroup specific oligonucleotide probes. This additional hybridisation assay increased the sensitivity of the RNA-PCR tenfold. The RNA-PCR was tested on clinical specimens from children with symptoms of an infection of the respiratory tract. The results were compared with isolation of RSV in cell culture and direct immunofluorescence. From 93 specimens tested, 31 were found positive by all three techniques. Six additional positive results were detected using RNA-PCR. From these 37 RSV positive specimens 33 (92%), including all 6 additional positives, were subgroup A and only 4 were subgroup B strains. Thus, the RNA-PCR is a specific and sensitive technique for the detection and subgroup classification of RSV genomes. PMID- 7798891 TI - Racial differences in the seroprevalence of hepatitis A virus infection in Natal/KwaZulu, South Africa. AB - The age- and race-specific seroprevalence of hepatitis A virus (HAV) infection was determined by radioimmunoassay (RIA) in 786 subjects between the ages of 6 months to 60 years. More than 50% of African children were seropositive by the age of 5 years. In blood donors (17-60 years), 50% (93/187) of Whites, 67% (110/163) of Indians, 85% (117/137) of Coloureds, and 91% (115/127) of Africans were seropositive. There was a significant difference in the seroprevalence of HAV infection between White blood donors and blood donors from the other three racial groups [Coloureds (P < 0.0001), Africans (P < 0.0001), and Indians (P < 0.001)] and between Indians and Coloureds (P < 0.0001) and Indians and Africans (P < 0.0001). There was no significance difference in HAV infection between Coloureds and Africans (P < 0.200). Eighty-seven per cent (32/37) of rural Africans had previous infection. In the African population HAV infection is acquired in childhood. There are significant racial differences in the seroprevalence of HAV infection. The surveillance of HAV infection may be used as a valuable yardstick to monitor the changing standards of hygiene and socioeconomic conditions of a community in transition in South Africa and to make rational public health decisions regarding a hepatitis A vaccination policy. PMID- 7798892 TI - Differences in the entire nucleotide sequence between hepatitis B virus genomes from carriers positive for antibody to hepatitis B e antigen with and without active disease. AB - The entire nucleotide sequence was determined for eight hepatitis B virus (HBV) genomes from three symptom-free carriers, two patients with chronic persistent hepatitis and one patient with chronic active hepatitis, who were positive for antibody to hepatitis B e antigen (HBeAg). The two patients with chronic persistent hepatitis were tested again after they developed chronic active or fulminant hepatitis, making a total of eight samples. Six had a point mutation in the preC region prohibiting the encoding of HBeAg precursor, while the remaining two had a deletion of 8 or 21 nucleotides within the X gene upstream of the preC transcription initiation sites which would affect the X gene and the putative preC/C promoter. Most genomes from the three symptom-free carriers and the two patients with chronic persistent hepatitis, with HBV DNA levels of 10(2) 10(3)/ml, had deletion, frameshift mutation, initiation failure or a premature stop codon, rendering them replication-incompetent. In contrast, such mutations were rarely seen in HBV genomes from the two patients with chronic persistent hepatitis after they had developed active or fulminant hepatitis and from the patient with chronic active hepatitis, all of whom had vigorous HBV replication with serum HBV DNA from 10(6) to 10(9)/ml. Unique mutations for amino acid changes were more frequent in HBV genomes with a higher replicative activity. These results indicate two kinds of HBV genomes with an HBeAg-minus phenotype, one with defects seriously affecting viral replication and the other without such defects, which would account for different clinical profiles in carriers with antibody to HBeAg. PMID- 7798893 TI - Enhanced synthesis of metallothionein as a possible cause of abnormal copper accumulation in LEC rats. AB - Long-Evans rats with a cinnamon-like coat color (LEC) is an inbred strain accumulating copper (Cu) in the liver abnormally and showing spontaneous hepatitis and hepatoma. The present study was intended to clarify how Cu accumulates in the LEC rat liver. For this purpose, the distribution profiles of Cu and zinc (Zn) and the inducibility of metallothionein (MT) synthesis were examined in the liver between Cu-loaded Long Evans agouti (LEA, the original strain of LEC) rats and were compared with those in control LEC rats. LEA rats (female, five weeks old) were injected subcutaneously with CuCl2 daily at a dose of 3 mg Cu/kg body weight for 2, 4, 6, and 9 days. The concentration of Cu (124 micrograms/g) accumulated in the LEA rat liver after four injections was comparable to that in control LEC rats. Only 20% of Cu in the liver of LEA rats was recovered in the supernatant fraction in the form of MT, while Cu in the LEC rat liver (113 micrograms/g) was recovered mostly in the supernatant fraction, and was bound to MT. Although the increased concentration of Cu in the LEA rat liver was further elevated after additional injections of Cu, the amount of MT did not increase further. The MT mRNA content in the LEA rat liver remained lower than that of LEC rats even after further injections of Cu. Therefore, the present results suggest that LEC rats can accumulate Cu at a high concentration in the liver because of their extremely high inducibility of MT. PMID- 7798894 TI - Purification and active-site characterization of equine plasma amine oxidase. AB - An improved purification scheme for an amine oxidase from equine plasma (EPAO), a nonruminant source, is described and the protein's active-site is characterized. EPAO is dimeric and contains one Type-2 Cu(II) ion per monomer. The EPAO Cu(II) site is spectroscopically very similar to the Cu(II) sites in other amine oxidases. Unlike the extensively investigated nonruminant amine oxidase from porcine plasma, EPAO does not display half-of-the-sites reactivity; titrations with p-nitrophenylhydrazine and phenylhydrazine indicate two active cofactors per dimer. This cofactor is determined to be the same as that of other copper containing amine oxidases, 6-hydroxydopa quinone (topa quinone). Upon anaerobic reduction with substrate at ambient temperature, the EPR spectrum of EPAO exhibits a sharp signal at g congruent to 2, attributable to the topa semiquinone. Equine plasma amine oxidase possesses novel in vitro substrate specificity; while other mammalian amine oxidases oxidize norepinephrine only slowly or not at all, EPAO displays significant activity toward this biogenic amine. PMID- 7798895 TI - Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH. AB - Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX). Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Thus, the spin trapping measurements provided no evidence for hydroxyl (.OH) radical generation in peroxynitrite decomposition at physiological pH. Thiols (glutathione, cysteine, and penicillamine) and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The one-electron oxidation of thiols by peroxynitrite may be one of the important mechanisms for peroxynitrite-induced toxicity and ascorbate may provide a detoxification pathway. PMID- 7798896 TI - Chromium toxicity in Neurospora crassa. AB - A comparative study has been made on the mechanisms of toxicities of trivalent and hexavalent forms of chromium in Neurospora crassa. Of the two forms, Cr6+ is more toxic than Cr3+. The toxicity of Cr3+ was found to be due to its specific antagonism with iron uptake. Fe3+ was found to be very effective in reversing the toxicity of Cr3+ by concomitantly suppressing its uptake. That the Cr3+ toxicity caused a conditional intracellular iron deficiency was indicated by the decrease in the activities of catalase and uricase and a progressive increase in the excretion of iron binding compound into the medium. The toxicity of Cr6+ (as Cr2O7(2-)) was found to be due to its specific antagonism of sulfate uptake. Methionine was found to be more effective in reversing dichromate toxicity than sulfate, probably by repressing the synthesis of sulfate permeases responsible for dichromate (Cr6+) uptake. Maximal uptake of Cr6+ was nearly tenfold lower and Vmax much higher than that of Cr3+. Evidence has been adduced to show that Cr6+ and Cr3+ were toxic by themselves and that interconversion between the tri- and hexavalent forms of chromium did not occur to any detectable extent. PMID- 7798897 TI - Vanadium in ascidians: changes in vanadium coordination and oxidation state upon cell lysis. AB - Changes in vanadium coordination during cell lysis have been followed by EPR spectroscopy of the blood cells of the phleborbranch ascidians Ascidia ceratodes and PHallusia julinea. The spectra obtained for A. ceratodes whole blood samples can be mainly ascribed to aquated oxovanadium(IV) in which the signals are broadened in freshly frozen blood relative to when the cells are lysed by thawing. The sources of this broadening are discussed and it is shown that the oxovanadium(IV) signal has its origin in a small percentage of damaged or lysed cells which release vanadium into a low sulfate, low acid environment in fresh samples. When thawed, the cells lyse releasing acid and sulfate into the environment of the oxovanadium(IV), with consequent narrowing of the EPR spectral linewidth. Freshly frozen P. julinea blood cell samples have EPR spectra with parameters intermediate between aquated oxovanadium(IV) and the "type I" parameters observed in a previous investigation of tissue samples of this species (S. G. Brand, C. J. Hawkins, A. T. Marshall, G. W. Nette, and D. L. Parry, Comp. Biochem. Physiol. 93B, 425 (1989)). A. ceratodes tissue samples also have EPR spectra that differ from that of the blood. It is suggested that EPR studies on tissue samples are more indicative of the resting state of vanadium in the cells as there is more physiological material to provide a pH buffering effect to stabilize the cells. Schemes are presented which incorporate all of the EPR observations in ascidian literature, where cellular lysis is proposed to be accompanied by vanadium undergoing oxidation and a series of chelate exchanges from a "type I" complex to aquated oxovanadium(IV). Protons released during these exchanges are suggested to provide the acidity characteristic of blood cell lysates. The biological implications of the concomitant release of vanadium and tunichrome (S. W. Taylor, D. L. Parry, C. J. Hawkins, and J. H. Swinehart, Comp. Biochem. Physiol. 106A, 531 (1993)) from the blood cells, to the process of wound repair are discussed. PMID- 7798898 TI - Kinetics of the reaction of platinum(II) complexes with metallothionein. PMID- 7798899 TI - Generation of SO3.- and OH radicals in SO3(2-) reactions with inorganic environmental pollutants and its implications to SO3(2-) toxicity. AB - Electron spin resonance (ESR) spin trapping and high performance liquid chromatography (HPLC) with electron chemical detection were utilized to investigate the generation of free radicals in reactions of sulfite (SO3(2-)) with inorganic environmental pollutants. The spin trap used was 5,5-dimethyl-1 pyrroline N-oxide (DMPO). Incubation of SO3(2-) with nitrite (NO2-) generated sulfur trioxide anion radical (SO3.-), whose yield approached saturation levels in approximately four minutes. Fe2+ promoted SO3.- formation. Molecular oxygen was required for radical generation. This was demonstrated by experiments carried out in an argon environment as well as by oxygen consumption measurements. Transition metal ions, CrO4(2-), VO2+, Fe3+, Mn2+, Ni2+, and Fe2+ enhanced SO3.- generation from SO3(2-) either through direct SO3(2-) oxidation by metal ions or by metal ions-catalyzed SO3(2-) oxidation by molecular oxygen. Incubation of SO3(2-) with H2O2 generated both SO3.- and .OH radicals as verified by spin trapping competition measurements using ethanol and formate as .OH radical scavengers. HPLC measurements showed that .OH radicals generated by reaction of SO3(2-) with H2O2 caused 2'-deoxyguanine hydroxylation to generate 8-hydroxy-2' deoxyguanine, a DNA damage marker. The implications of SO3.- and .OH radical formation in relation to SO3(2-) toxicity are discussed. PMID- 7798901 TI - Effect of Hg(II) on the spectroscopic properties of DNA bases: circular dichroism of deoxyadenosine and thymidine monomers and dimers. AB - The addition of Hg(ClO4)2(Hg(II)) to 2'-deoxyadenosine (dA), thymidine (dT), to their respective 5'-monophosphates (dAp,dTp) as well as to the dinucleoside phosphates 2'-deoxyadenylyl-(3'-->5')-2'-deoxyadenosine (d(ApA)), 2-deoxyadenylyl (3'-->5')thymidine(d(ApT)), thymidylyl-(3'-->5')-2'-deoxyadenosine (d(TpA)), and thymidylyl-(3'-->5')thymidine (d(TpT))--all dissolved in 0.1 M NaClO4, 5 mM cacodylic acid buffer, pH 7--produces major alterations in the circular dichroism (CD) of the dimers but no or only small changes in the CD of the monomers. Of particular interest are the Hg(II)-induced changes in the CD of d(ApT) and d(TpA): they are strongly sequence-dependent and, within reason, progress in a "mirror"-like fashion when the concentration of Hg(II) is varied. In the absence of Hg(II), the CD of the dimers is conservative (d(TpT)), or near-conservative (d(ApA), d(ApT), d(TpA)), but becomes nonconservative upon the addition of Hg(II). The rotational strength R of the various Cotton effects of the dimers was evaluated as a function of Hg(II) concentration. Features of the CD spectra of mercurated d(ApA) and d(TpT) persist in the CD spectra of mercurated poly[d(A).(T)], but there is little obvious agreement of the CD spectra of mercurated d(ApT) and d(TpA) with the CD of mercurated poly[d(A-T).d(A-T)]. PMID- 7798900 TI - Iron core formation in horse spleen ferritin: magnetic susceptibility, pH, and compositional studies. AB - Horse spleen ferritin (HoSF) reconstituted with small iron cores ranging in size from 8 to 500 iron atoms was studied by magnetic susceptibility and pH measurements to determine when the added Fe3+ begins to aggregate and form antiferromagnetically coupled clusters and also to determine the hydrolytic state of the iron at low iron loading. The Evans NMR magnetic susceptibility measurements showed that at iron loadings as low as 8 Fe3+/HoSF, at least half of the added iron atoms were involved in antiferromagnetic exchange interactions and the other half were present as isolated iron atoms with S = 5/2. As the core size increased to about 24 iron atoms, the antiferromagnetic exchange interactions among the iron atoms increased until reaching the limiting value of 3.8 Bohr magnetons per iron atom, the value present in holo HoSF. HoSF containing eight or more Fe3+ to which eight Fe2+ were added showed that the Fe2+ ions were at sites remote from the Fe3+ and that the resulting HoSF consisted of individual, noninteracting Fe2+ and the partially aggregated Fe3+. pH measurements for core reduction showed that Fe(OH)3 was initially present at all iron loadings but that in the absence of iron chelators the reduced iron core is partially hydrolyzed. Proton induced x-ray emission spectroscopy showed that Cl- is transported into the iron core during reduction, forming a stable chlorohydroxy Fe(II) mineral phase. PMID- 7798902 TI - Isolation and expression of an arrestin cDNA from the horseshoe crab lateral eye. AB - Electrophysiological studies of photoreceptors from the horseshoe crab Limulus polyphemus continue to provide fundamental new knowledge of the photoresponse in invertebrates. Therefore, it is of particular interest to characterize the molecular components of the photoresponse in this system. Here we describe an arrestin cloned from a cDNA library constructed using poly(A)+ RNA isolated from Limulus lateral eyes. The protein, deduced from the arrestin cDNA, is most similar to arrestin from locust antennae (56% identity) and Drosophila phosrestin I (53% identity). Limulus arrestin was expressed in a heterologous system, and its properties were compared with those of a 46-kDa light-regulated phosphoprotein (pp46A) in Limulus photoreceptors described in previous studies from this laboratory. Arrestin and pp46A (a) have the same apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (b) have an isoelectric point in the basic pH range, (c) require calmodulin and elevated Ca2+ levels for phosphorylation, (d) are immunoreactive with monoclonal antibody C10C10 directed against a sequence in bovine arrestin (S-antigen) that is perfectly conserved in the deduced arrestin protein, and (e) are associated with photoreceptors. We conclude that the arrestin described here and pp46A are the same protein. The results of this and previous studies show that in Limulus photoreceptors, light regulates the phosphorylation of arrestin in complex ways. PMID- 7798903 TI - Activation of metabotropic glutamate receptors prevents neuronal apoptosis in culture. AB - Cultured granule cells grown in serum-containing medium with a "low K+" concentration (10 mM) underwent apoptosis after maturation for 5 days in vitro (5 DIV), a time that coincides with the developmental decline in the activity of metabotropic glutamate receptors (mGluRs) coupled to polyphosphoinositide hydrolysis. The mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) prevented the development of low K(+)-induced apoptosis and the presence of the drug was critical at 6 and 7 DIV, i.e., after the drop of mGluR activity. The neuroprotective action of 1S,3R-ACPD was prevented by the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) and was mimicked by N methyl-D-aspartate or carbamylcholine but not by agonists of the mGluR subtypes negatively linked to adenylyl cyclase. In cultures treated either with Li(+) which reduced polyphosphoinositide response to concentrations of glutamate (5 microM) that approximate those physiologically present in the incubation medium- or MCPG, the development of low K(+)-induced apoptosis already occurred at 4 DIV. Thus, the activation of mGluRs coupled to polyphosphoinositide hydrolysis by endogenous glutamate could contribute to protect cultured granule cells against apoptosis during early stages of maturation. PMID- 7798904 TI - Developmental characterization of thymosin beta 4 and beta 10 expression in enriched neuronal cultures from rat cerebella. AB - The beta 4 and beta 10 thymosins are G-actin binding proteins that exhibit complex patterns of expression during rat cerebellar development. Their expression in vivo is initially high in immature granule cells and diminishes as they migrate and differentiate, ceasing altogether by postnatal day 21. Thymosin beta 4 is present in a subset of glia throughout postnatal development, and its synthesis is also induced in maturing Bergmann glia. In contrast, thymosin beta 10 is only present at very low levels in a very small subpopulation of glia in the adult cerebellum. To study the factors differentially regulating expression of the beta-thymosins, we characterized their patterns of expression in primary cultures of rat cerebellum. Both beta-thymosins were initially expressed in granule cells, although expression, especially of thymosin beta 4, was truncated compared with the in vivo time course. As in vivo, thymosin beta 4 was synthesized at much higher levels in astrocytes and microglia in cultures from postnatal cerebellum than was thymosin beta 10. Unlike in vivo, the latter was expressed in glia cultured from fetal cerebellum. The similarities between the in vivo and in vitro expression of the beta-thymosins show that modulation of tissue culture conditions could be used to identify factors regulating beta-thymosin expression in vivo. The differences would identify regulatory mechanisms that are not evident from the in vivo studies alone. PMID- 7798905 TI - myc-immortalized microglial cells express a functional platelet-activating factor receptor. AB - The autacoid platelet-activating factor (PAF) takes part in a complex network of interactions regarding the cellular components of nervous tissues. Efforts aimed at characterizing the effects of PAF in the brain have been recently focalized on neurons because PAF exerts pleiotropic effects on these cells. Less attention has instead been paid to the glial component of the brain. We have used microglial cell lines immortalized from 13-day-old mouse embryo brains by a myc-transducing retrovirus. When exposed to physiological doses of PAF, immortalized microglial cells showed increases in intracellular free calcium concentrations due to release of calcium from internal stores, as well as to extracellular calcium influxes. These profiles of reactivity were independent from the immortalizing process, being observable in primary microglial cultures and in immortalized clones showing different proliferative rates. PAF was also able to induce transient expression of the c-fos protooncogene in serum-starved cultures and induced a strong chemotactic response in microglial cells. In contrast with control macrophage cultures, PAF did not promote prostaglandin or leukotriene synthesis in immortalized cells. This was most likely due to the low amount of total arachidonic acid found in immortal microglia, with respect to that observed in freshly isolated cells. Our data suggest that several of the effects observed after PAF stimulation might be independent from PAF-induced arachidonic acid metabolism. The availability of an in vitro microglial model might now help in studying the proinflammatory effects of PAF, both direct or microglia mediated, in the neural environment. PMID- 7798906 TI - Melatonin receptor-mediated stimulation of phosphoinositide breakdown in chick brain slices. AB - The direct effect of melatonin and related agonists on Li(+)-amplified phosphoinositide breakdown was studied in chick brain slices prelabeled with myo [2-3H]-inositol. The melatonin receptor agonist 6-chloromelatonin (10-100 microM) increased, in a concentration-dependent manner, the accumulation of inositol phosphates (IP) in chick brain slices. This effect of 6-chloromelatonin (10 microM) was rapid as transient increases in IP3/IP4 (maximal increase, 29% at 20 s) and IP2 levels (maximal increase, 36% at 1 min) were observed, followed by a slower but sustained increase in IP1 level (30% at 5 min), when the amount of IP3/IP4 and IP2 had already been decreased to the control level. The phosphoinositide response elicited by 6-chloromelatonin (10 microM) was dependent on the presence of extracellular calcium. Direct stimulation of membrane phospholipase C by 6-chloromelatonin (10 microM) in isolated myo-[2-3H]inositol prelabeled optic tectum membranes was dependent on the presence of guanosine-5'-O (3-thio)triphosphate (1 microM), thus suggesting that G protein(s) link melatonin receptor activation to phospholipase C stimulation. The competitive melatonin receptor antagonist luzindole (10-100 microM) inhibited in a concentration dependent manner the IP1 accumulation stimulated by 6-chloromelatonin (10-100 microM); however, it did not affect the accumulation stimulated by 5 hydroxytryptamine (10 microM). By contrast, methysergide (10 microM) completely inhibited 5-hydroxy-tryptamine (10 microM)-, but not 6-chloromelatonin (10 microM)-, induced IP1 accumulation. Melatonin receptor agonists increased IP1 accumulation in a concentration-dependent manner reaching different maximal responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798907 TI - Isolation and characterization of a cytosolic phospholipase A2 from bovine adrenal medulla. AB - We have recently demonstrated that bovine adrenal medulla contains a soluble phospholipase A2 (PLA2), which is localized in the cytosol. In the present study, this PLA2 was purified 1,097-fold using sequential concanavalin A, hydrophobic interaction, anion exchange, gel filtration, and an additional anion exchange chromatography. The enzyme is activated over the range of 20-1,000 microM Ca2+ and has a pH optimum near 8.0. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein has a molecular mass of 26 kDa and an isoelectric point of 4.6 as revealed by isoelectric focusing. The cytosolic PLA2 is not inhibited by NaCl, and the enzymatic activity is stimulated at low concentrations of Triton X-100 (0.01%) and deoxycholate (1 mM) but inhibited at higher concentrations (0.1% and 3 mM, respectively) of these detergents. Furthermore, heat treatment (57 degrees C, 5 min) reduced the enzymatic activity by 80%, whereas glycerol (30%) increased the activity. p-Bromophenacylbromide, a frequently used irreversible inhibitor of type II PLA2, has little effect until 100 microM, and 2-10 mM dithiothreitol totally inactivated the enzyme. The purified PLA2 displays a preference for phosphatidylcholine as a substrate but hydrolyzes phospholipid substrates with arachidonic acid or linoleic acid esterified at the sn-2 position to the same extent. It is concluded that the chromaffin cell cytosolic PLA2, which was isolated and characterized in this study, represents a type of PLA2 that has not been formerly reported in chromaffin cells. Additional research on the chromaffin cell cytosolic PLA2 will help to reveal whether the enzyme is important for exocytosis. PMID- 7798908 TI - Characterization and distribution of a cloned rat mu-opioid receptor. AB - We have cloned and expressed a rat brain cDNA, TS11, that encodes a mu-opioid receptor based on pharmacological, physiological, and anatomical criteria. Membranes were prepared from COS-7 cells transiently expressing TS11 bound [3H]diprenorphine with high affinity (KD = 0.23 +/- 0.04 nM). The rank order potency of drugs competing with [3H]diprenorphine was as follows: levorphanol (Ki = 0.6 +/- 0.2 nM) approximately beta-endorphin (Ki = 0.7 +/- 0.05 nM) approximately morphine (Ki = 0.8 +/- 0.5 nM) approximately [D-Ala2, N-Me-Phe4,Gly ol5]-enkephalin (DAMGO; Ki = 1.6 +/- 0.5 nM) uch much greater than U50,488 (Ki = 910 +/- 0.78 nM) > [D-Pen2,5]- enkephalin (Ki = 3,170 +/- 98 nM) > dextrorphan (Ki = 4,100 +/- 68 nM). The rank order potencies of these ligands, the stereospecificity of levorphanol, and morphine's subnanomolar Ki are consistent with a mu-opioid binding site. Two additional experiments provided evidence that this opioid-binding site is functionally coupled to G proteins: (a) in COS-7 cells 50 microM 5'-guanylylimidodiphosphate shifted a fraction of receptors with high affinity for DAMGO (IC50 = 3.4 +/- 0.5 nM) to a lower-affinity state (IC50 = 89.0 +/- 19.0 nM), and (b) exposure of Chinese hamster ovary cells stably expressing the cloned mu-opioid receptor to DAMGO resulted in a dose-dependent, naloxone-sensitive inhibition of forskolin-stimulated cyclic AMP production. The distribution of mRNA corresponding to the mu-opioid receptor encoded by TS11 was determined by in situ hybridization to brain sections prepared from adult female rats. The highest levels of mu-receptor mRNA were detected in the thalamus, medial habenula, and the caudate putamen; however, significant hybridization was also observed in many other brain regions, including the hypothalamus. PMID- 7798909 TI - Uptake and release of D-aspartate, GABA, and glycine in guinea pig brainstem auditory nuclei. AB - This study attempts to determine if the medial (MSO) and lateral superior olive (LSO), medial nucleus of the trapezoid body (MNTB), ventral nucleus of the lateral lemniscus (VNLL), and central nucleus of the inferior colliculus (ICc) contain glutamatergic synaptic endings. Micropunch and microdissection procedures provided fresh samples of these auditory nuclei for the measurement of the high affinity uptake and electrically evoked release of exogenous D-[3H]ASP. The study also determined if the LSO and MSO contain glycinergic synaptic endings by measuring uptake and release of [14C]Gly in these nuclei, and whether the MNTB, VNLL, and ICc contain GABAergic endings by assessing the uptake and release of [14C]GABA in these structures. Several strategies optimized the evoked Ca(2+) dependent release of the labeled amino acids. These included the enhancement of high-affinity uptake during loading of the markers into the tissues, inhibition of uptake during the subsequent measurement of release, and use of an electrical stimulus current that evoked maximal Ca(2+)-dependent release. Each of these nuclei manifested the high-affinity uptake and the evoked Ca(2+)-dependent release of D-[3H]Asp, suggesting the presence of synaptic endings that may use Glu or Asp as a transmitter. Similar findings suggest the presence of glycinergic synaptic endings in the LSO and MSO, and of GABAergic synaptic endings in the MNTB, VNLL, and ICc. PMID- 7798911 TI - Persistent enhancement of sustained calcium-dependent glutamate release by phorbol esters: requirement for localized calcium entry. AB - Sustained activation of protein kinase C significantly enhanced a secondary (slow) phase in the depolarization-induced release of glutamate from isolated hippocampal nerve endings. The phorbol ester, 4 beta-phorbol 12,13-dibutyrate, was used to sustain the activation of presynaptic protein kinase C for a prolonged (10-min) period, and then this relatively water-soluble phorbol ester was removed by superfusion before a 2-min stimulus of continuous membrane depolarization. These conditions were used to investigate the persistent effects of sustained protein kinase C activation on the magnitude of the slow phase of evoked glutamate release, in which the efficiency of synaptic vesicle mobilization and recycling may be primary determinants of response magnitude. It is reported here that sustained protein kinase C activation selectively increased the Ca(2+)-dependent component of glutamate release during a prolonged phase of K(+)-induced depolarization. The magnitude of this persistent effect on Ca(2+) dependent glutamate release was directly related to the dose of 4 beta-phorbol 12,13-dibutyrate and the duration of exposure that was used to prime the release apparatus, was observed using two alternative synaptosomal preparations, and was evident regardless of the depolarizing stimulus used (elevated [KCl] or 4 aminopyridine). However, 4 beta-phorbol 12,13-dibutyrate did not alter the release induced by the Ca2+ ionophore ionomycin. Thus, the persistent effects of protein kinase C activation on a prolonged phase of glutamate release were dependent on the route of Ca2+ influx. The finding that voltage-regulated Ca2+ channel blockers were able to neutralize completely the 4 beta-phorbol 12,13 dibutyrate-dependent facilitation of K(+)-evoked glutamate release provided further support for this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798910 TI - Evidence for glutamatergic projections from the cochlear nucleus to the superior olive and the ventral nucleus of the lateral lemniscus. AB - This study attempts to determine if projections ascending from the guinea pig cochlear nucleus (CN) could be glutamatergic and/or aspartatergic. Multiple radio frequency lesions were made to ablate the right CN. The ablation was verified histologically. To identify the principal targets of CN efferents, silver impregnation methods were used to localize the preterminal degeneration of fibers in transverse sections of the brainstem 5 and 7 days after CN ablation. CN efferents projected heavily to the lateral superior olive (LSO) ipsilaterally, the medial superior olive (MSO) bilaterally, and contralaterally to the medial (MNTB) and ventral (VNTB) nuclei of the trapezoid body, the ventral (VNLL) and intermediate nuclei of the lateral lemniscus and the central nucleus of the inferior colliculus (ICc). There were smaller projections to the lateral nucleus of the trapezoid body ipsilaterally, the dorsal and dorsomedial periolivary nuclei bilaterally, and the dorsal nucleus of the lateral lemniscus contralaterally. There were sparse projections to the VNLL and ICc ipsilaterally and the CN contralaterally, and a very sparse projection to the contralateral LSO. To determine if CN efferents were glutamatergic and/or aspartatergic, the fresh brainstem was sectioned transversely and samples of the LSO, MSO, MNTB, VNLL, and ICc were taken to measure the electrically evoked release and the uptake of D-[3H]Asp and [14C]Gly or [14C]GABA 3-5 days after the CN ablation. The release studies suggest that only certain of the histologically identified projections ascending from the CN may be glutamatergic and/or aspartatergic. CN ablation depressed D-[3H]Asp release in the MSO bilaterally and in the contralateral MNTB and VNLL, suggesting that the CN efferents to these nuclei may use glutamate or aspartate as a transmitter. It was unclear whether a marginal depression of D-[3H]Asp release in the ipsilateral LSO reflected the presence of glutamatergic CN projections to this nucleus. D-[3H]Asp release in the ICc was unaffected, suggesting that CN efferents to this nucleus may not be glutamatergic. There were no deficits in D-[3H]Asp uptake. [14C]Gly release from the LSO and MSO was unchanged. [14C]Gly uptake was unchanged in the MSO and depressed only in the contralateral LSO, possibly reflecting subnormal uptake activity in endings contributed by contralateral MNTB cells that had lost their CN efferents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798912 TI - Persistent enhancement of sustained calcium-dependent glutamate release by phorbol esters: role of calmodulin-independent serine/threonine phosphorylation and actin disassembly. AB - The phorbol ester 4 beta-phorbol 12,13-dibutyrate increases the final extent of Ca(2+)-dependent glutamate release during the continuous depolarization of the synaptosomal plasma membrane. Based on this finding, we suggested that the sustained activation of protein kinase C has a positive influence on the efficiency of synaptic vesicle recycling in the presence of saturating concentrations of Ca2+. Previous work from our laboratory demonstrated that this 4 beta-phorbol 12,13-dibutyrate-dependent enhancement of synaptic vesicle recycling persists following the removal of 4 beta-phorbol 12,13-dibutyrate, requires localized Ca2+ entry through voltage-regulated channels, and is insensitive to the protein kinase inhibitor staurosporine. In the present study, we examined the possibility that the facilitation of glutamate release may be propagated through interactions between the protein kinase C- and multifunctional Ca2+/calmodulin-dependent protein kinase pathways. However, our data argue strongly against the involvement of such a mechanism in the persistent enhancement of sustained glutamate release. We observed that 4 beta-phorbol 12,13 dibutyrate did not increase the availability of cytosolic free calmodulin or the level of autonomous Ca2+/calmodulin-dependent protein kinase activity. In addition, we determined the effects of various serine/threonine kinase and phosphatase inhibitors on the phorbol ester-dependent enhancement of sustained glutamate release and found that protein kinase C increased the extent, but not the duration, of Ca(2+)-dependent glutamate release through a kinase-independent mechanism. Given our finding that the actin-depolymerizing agent cytochalasin D totally occluded the eb1ect of 4 beta-phorbol 12,13-dibutyrate on release, we postulate that protein kinase C signals may be transduced through direct interactions between protein kinase C isoforms and cytoskeletal protein kinase C binding proteins. PMID- 7798914 TI - Serotonin 5-HT2C receptor stimulates cyclic GMP formation in choroid plexus. AB - The serotonin 5-HT2C receptor (formerly designated the 5-HT1C receptor) of the choroid plexus triggers phosphoinositide turnover. In the present study, we demonstrate that receptor activation also triggers the formation of cyclic GMP (cGMP). Application of 1 microM 5-HT to porcine choroid plexus tissue slices resulted in stimulation of cGMP formation to a maximum of five-fold basal level, with an EC50 of 11 nM. This response was not inhibited by muscarinic or beta adrenergic receptor antagonists. Serotonin receptor antagonists inhibited cGMP formation with apparent Ki values of 1.3 (mianserin), 200 (ketanserin), and 5,500 (spiperone) nM, respectively. Neither serotonin-stimulated cGMP formation nor PI turnover was inhibited by pertussis toxin pretreatment. Preliminary biochemical studies suggested that serotonin-stimulated cGMP formation was calcium, phospholipase A2, and lipoxygenase dependent, as incubation in low calcium buffers or inclusion of the phospholipase A2 or lipoxygenase inhibitors p bromophenacylbromide or BW 755c resulted in significant reduction of cGMP formation. The present results suggest that in addition to triggering phosphoinositide turnover, choroid plexus serotonin 5-HT2C receptors trigger cGMP formation in a calcium-sensitive manner. PMID- 7798913 TI - Dopamine transporter-dependent and -independent endogenous dopamine release from weaver mouse striatum in vitro. AB - The weaver mutant mouse (wv/wv) has an approximately 70% loss of nigrostriatal dopamine (DA) neurons, but the fractional DA release evoked by amphetamine (but not a high potassium level) has been shown to be greater from striatal slices of the weaver compared with +/+ mice. In the present work we tested the hypothesis that fractional DA release from weaver striatum would be greater when release was mediated by the DA transporter. Serotonin (5-HT)-stimulated fractional DA release was greater from weaver than from +/+ striatum. The release evoked by 5-HT in the presence of 10 microM nomifensine (an antagonist of the DA transporter) was less than in its absence, but the difference between weaver and +/+ striatum remained. In the presence of nomifensine, 1-(m-chlorophenyl)biguanide, classified as a 5 HT3 agonist, also induced a greater fractional release from weaver compared with +/+ striatum. When veratridine was used at a low concentration (1 microM), the fractional evoked release of DA was higher from the weaver in the presence and absence of nomifensine. These findings suggest that the reason for the difference in the responsiveness of the two genotypes to these release-inducing agents is not related to DA transporter function. PMID- 7798915 TI - Glucocorticoids enhance histamine-evoked catecholamine secretion from bovine chromaffin cells. AB - The synthetic glucocorticoid dexamethasone enhanced histamine-evoked catecholamine secretion from cultured bovine chromaffin cells. Dexamethasone enhanced the effects of histamine on both adrenergic (epinephrine-rich) and noradrenergic (norepinephrine-rich) chromaffin cells but had a more dramatic effect on noradrenergic cells. Histamine-evoked secretion in noradrenergic cells appeared to become rapidly inactivated, whereas the rate of secretion in adrenergic cells was nearly constant for up to 2 h; dexamethasone treatment attenuated the inactivation seen in noradrenergic cells. The effect of dexamethasone appeared after a lag of several hours and was maximal by 24 h. The EC50 for dexamethasone was approximately 1 nM. The effect of dexamethasone was mimicked by the glucocorticoid agonist RU 28362 and was blocked by the antagonist RU 38486, indicating that the effects of these steroids were mediated by the glucocorticoid or type II corticosteroid receptor. Histamine-evoked catecholamine secretion in both dexamethasone-treated and untreated cells was blocked by the H1 histamine receptor antagonist mepyramine but was not affected by the H2 antagonist cimetidine; thus, dexamethasone appeared to enhance an H1 receptor mediated process. In the absence of glucocorticoids, H1 receptor mRNA levels were higher in adrenergic than in noradrenergic cells. Dexamethasone increased H1 receptor mRNA levels in both cell types. The increased expression of H1 receptors presumably contributes to the enhancement of histamine-evoked catecholamine secretion by glucocorticoids. Glucocorticoids may play a physiological role in modulating the responsiveness of chromaffin cells to histamine and other stimuli. PMID- 7798916 TI - Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line. AB - There has been considerable interest and controversy in the relationship between nerve growth factor (NGF) and the cyclic AMP (cAMP) second messenger system. We have used a novel, neuronal cell line (HT4) to investigate the effect of NGF on the adenylyl cyclase signaling system. Treatment of cells with NGF (100 ng/ml, 15 min) amplified cAMP accumulation (approximately 75%) in response to activation of adenosine A2 receptors (5 min) with 5'-N-ethylcarboxamidoadenosine or activation of adenylyl cyclase directly with forskolin. Basal cAMP accumulation was not altered by NGF. This amplification appears to be mediated by activation of protein kinase C (PKC) because (1) it was mimicked by activators (phorbol esters and a diacylglycerol analogue) of PKC, (2) the effects of NGF and phorbol ester on cAMP accumulation were not additive, (3) NGF amplification of cAMP accumulation was abolished by down-regulation of PKC, (4) NGF increased cytosolic PKC activity, and (5) inhibitors of PKC blocked the NGF-induced amplification of cAMP accumulation. Although NGF-induced amplification of cAMP accumulation was dependent upon PKC, mechanisms other than the classic activation pathway (i.e., hydrolysis of inositol phospholipids or the production of diacylglycerol) appeared to mediate PKC activation by NGF. The tyrosine kinase inhibitor, lavendustin A, blocked NGF-mediated amplification of cAMP accumulation, suggesting a novel interaction between a tyrosine kinase and protein kinase C. PMID- 7798917 TI - Intracerebral dialysis and the blood-brain barrier. AB - The aim of the study was to evaluate how implantation of a dialysis probe influences the blood-brain barrier. Leakage of endogenous serum albumin was evaluated by Evans blue/albumin staining and by immunohistochemistry. The passage from blood to dialysate of two substances that normally do not pass into the brain, [3H]-inulin and glutamate, was studied 3 and 24 h after insertion of a dialysis probe. Evans blue, given 20 min before rats were killed, was observed around the probe and surrounding brain tissue. Albumin immunoreactivity was seen at considerable distance from the probe with larger spread at 24 h than at 3 h after probe insertion. Glutamate and [3H]inulin were detected in the dialysate with no significant further increase of radioactivity after intracarotid infusion of protamine sulfate that enhances the permeability over the blood-brain barrier. When protamine was followed by infusion of glutamate, the concentrations of taurine increased in the dialysate in four of eight rats. That plasma constituents have access to the brain around the dialysis probe is essential to consider, particularly in studies using substances and drugs that do not pass an intact blood-brain barrier. PMID- 7798918 TI - Heat-shock 70 messenger RNA levels in human brain: correlation with agonal fever. AB - Systematic review of antemortem clinical information on randomly selected Alzheimer disease (AD) patients revealed that approximately 40% of the patients had a recorded fever of > or = 39.2 degrees C at or near death. Using isolation and quantitation techniques appropriate for analysis of human brain mRNAs, we found that low levels of inducible heat-shock protein 70 (hsp70) mRNAs were present in cerebellum of afebrile AD patients and that mRNA levels were usually lower in two brain regions affected in AD, i.e., hippocampus and temporal cortex. Levels of hsp70 mRNAs were increased three- to 33-fold in cerebellum of febrile patients compared with levels in patients whose recorded temperatures were < or = 37.5 degrees C. Levels of hsp70 mRNAs were also increased in hippocampus and cortex of these febrile patients, but to a lesser extent than cerebellum. Heat shock cognate 70 (hsc70) mRNAs were present at highest levels in afebrile cerebellum and were also present in the other brain regions. In cerebellum of patients with the highest temperatures, hsc70 mRNAs were induced severalfold over basal levels. Although there was a low and variable induction of hsc70 mRNAs in temporal cortex of these patients, there was no evidence for any induction in hippocampus. Increased heat-shock 70 mRNA levels did not correlate with hypoxia, coma, hypertension, hypoglycemia, seizures, or medication. These results indicate that a specific agonal stress, namely fever, can increase the levels of heat shock 70 mRNAs in AD brain; however, there is no evidence to suggest that affected regions of AD brain have higher overall levels of these mRNAs. Failure to obtain adequate agonal state information could result in inaccurately identifying short-term stress-related changes in postmortem brain as neuropathology characteristic of a chronic disease state. PMID- 7798919 TI - Loss of protein kinase C-alpha beta in brain of heroin addicts and morphine dependent rats. AB - The biochemical status of human brain protein kinase C (PKC)-alpha beta during opiate dependence was studied by means of immunoblotting techniques in postmortem brain of heroin addicts who had died by opiate overdose. In the frontal cortex, a marked decrease (53%, p < 0.05) in the immunoreactivity of PKC-alpha beta was found in heroin addicts compared with matched controls. The loss of PKC-alpha beta in the brain of human addicts paralleled that observed in the frontal cortex of rats after chronic treatment with morphine (10-100 mg/kg i.p. for 5 days) (PKC alpha beta decreased by 34%, p < 0.05). Chronic treatment with naloxone (1 mg/kg i.p. every 12 h for 5 days) did not alter PKC-alpha beta immunoreactivity in the rat brain. However, in morphine-dependent rats, naloxone-precipitated withdrawal induced a rapid and strong behavioral reaction with a concomitant up-regulation of PKC-alpha beta immunoreactivity to control values. These results indicated that the decrease of brain PKC-alpha beta induced by heroin/morphine is a mu opioid receptor-mediated effect. The chronic administration of opiates has been associated with a marked sensitization of the adenylyl cyclase/cyclic AMP system, although this phenomenon is not exclusive of the opioid system but the general cellular adaptation to chronic inhibition of adenylyl cyclase. In this context, chronic treatment of rats with other inhibitory agonists (e.g., clonidine, 1 mg/kg i.p. every 12 h for 14 days) acting through receptors (e.g., alpha 2 adrenoceptors) also coupled to adenylyl cyclase did not alter brain PKC-alpha beta immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798920 TI - Mutagenesis of rat dopamine beta-hydroxylase: examination in cell-free system. AB - Dopamine beta-hydroxylase (DBH; EC 1.14.17.1) exists as membrane-bound and soluble forms in neurosecretory vesicles. The features of DBH required for glycosylation and incorporation into membranes were studied in a cell-free system. Translation of full-length DBH with microsomal membranes generated two glycosylated products (GH and GL) depending on the magnesium concentration. Carboxyl-terminal, in contrast to amino-terminal, truncations gave translation products that were glycosylated by microsomal membranes. Site-directed mutants were generated with the second AUG codon and the region of a putative signal sequence cleavage site modified. Translation without membranes indicated that the second AUG is not used to initiate translation. The mutant with Glu41-->Leu41 and Ser43-->Thr43 yielded only the GH form with membranes, whereas mutation of Ser43- >Ala43 generated both GH and GL forms. Both glycosylated forms comigrated with the microsomal membranes on sucrose gradients. Endoglycosidase H digestion indicated that the differences between the GH and GL forms are not due to the sugar moiety. The results suggest a role for cleavage of a signal sequence in the formation of different forms of DBH. The possibility that these mutations change the secondary structure near the signal cleavage site, affecting processing, is discussed. PMID- 7798922 TI - Inflammatory mediator stimulation of astrocytes and meningeal fibroblasts induces neuronal degeneration via the nitridergic pathway. AB - The role of inflammatory cytokines in the pathogenesis of neurological disorders is not entirely clear. The neurotoxic effects of cytokines, and perhaps indirectly bacterial endotoxins, could be mediated by the stimulation of immunocompetent cells in the brain to produce toxic concentrations of nitric oxide (NO) and reactive nitrogen oxides. NO is a short-lived, diffusible molecule that has a variety of biological activities including vasorelaxation, neurotransmission, and cytotoxicity. Both constitutive and inducible NO synthase has been described in astrocytes in vitro. Here we demonstrate that newborn mouse cortical astrocytes, when coincubated with neonatal mouse cerebellar granule cells or hippocampal neurons, induced neurotoxicity upon stimulation with endotoxin (lipopolysaccharide) (ED50 30 ng/ml). Astrocytes were unresponsive to the cytokines tumor necrosis factor-alpha or interleukin-1 beta individually, but exhibited a marked synergistic stimulation in their combined presence. Moreover, meningeal fibroblasts treated with tumor necrosis factor-alpha, but not interleukin-1 beta or lipopolysaccharide, elaborated neurotoxicity for cocultured granule cells (ED50 30 U/ml). In cocultures of immunostimulated astrocytes or meningeal fibroblasts, neurotoxicity was blocked by the NO synthase inhibitors N omega-nitro-L-arginine and N omega-nitro-D-arginine methyl ester, and by oxyhemoglobin, which inactivates NO. Astroglial-induced neurotoxicity was not affected by N-methyl-D-aspartate receptor antagonists. Superoxide dismutase, which degrades superoxide anion, attenuated astrocyte- and fibroblast-mediated neurotoxicity, indicating that endogenous superoxide anion may react with NO to form toxic peroxynitrite and its breakdown products. These findings suggest a potentially important role for glial- and meningeal fibroblast-induced NO synthase in the pathophysiology of CNS disease states of immune or inflammatory origin. PMID- 7798921 TI - Structure-activity analyses of beta-amyloid peptides: contributions of the beta 25-35 region to aggregation and neurotoxicity. AB - The neurodegeneration of Alzheimer's disease has been theorized to be mediated, at least in part, by insoluble aggregates of beta-amyloid protein that are widely distributed in the form of plaques throughout brain regions affected by the disease. Previous studies by our laboratory and others have demonstrated that the neurotoxicity of beta-amyloid in vitro is dependent upon its spontaneous adoption of an aggregated structure. In this study, we report extensive structure-activity analyses of a series of peptides derived from both the proposed active fragment of beta-amyloid, beta 25-35, and the full-length protein, beta 1-42. We examine the effects of amino acid residue deletions and substitutions on the ability of beta-amyloid peptides to both form sedimentable aggregates and induce toxicity in cultured hippocampal neurons. We observe that significant levels of peptide aggregation are always associated with significant beta-amyloid-induced neurotoxicity. Further, both N- and C-terminal regions of beta 25-35 appear to contribute to these processes. In particular, significant disruption of peptide aggregation and toxicity result from alterations in the beta 33-35 region. In beta 1-42 peptides, aggregation disruption is evidenced by changes in both electrophoresis profiles and fibril morphology visualized at the light and electron microscope levels. Using circular dichroism analysis in a subset of peptides, we observed classic features of beta-sheet secondary structure in aggregating, toxic beta-amyloid peptides but not in nonaggregating, nontoxic beta amyloid peptides. Together, these data further define the primary and secondary structures of beta-amyloid that are involved in its in vitro assembly into neurotoxic peptide aggregates and may underlie both its pathological deposition and subsequent degenerative effects in Alzheimer's disease. PMID- 7798923 TI - Persistent translocation of Ca2+/calmodulin-dependent protein kinase II to synaptic junctions in the vulnerable hippocampal CA1 region following transient ischemia. AB - The influence of brain ischemia on the subcellular distribution and activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) was studied in various cortical rat brain regions during and after cerebral ischemia. Total CaM kinase II immunoreactivity (IR) and calmodulin binding in the crude synaptosomal fraction of all regions studied increase but decrease in the microsomal and cytosolic fractions, indicative of a translocation of CaM kinase II to synaptosomes. The translocation of CaM kinase II to synaptic junctions occurs but not to synaptic vesicles. The translocation in neocortex and CA3/DG (dentate gyrus) is transient, whereas in the hippocampal CA1 region, it persists for at least 1 day of reperfusion. The Ca2+/calmodulin-dependent activity of CaM kinase II in the subsynaptosomal fractions of neocortex is persistently decreased by up to 85%, despite the increase in CaM kinase II IR. The decrease in activity is more pronounced than the decline in IR, suggesting that CaM kinase II is covalently modified in the postischemic phase. The persistent translocation of CaM kinase II in the vulnerable ischemic CA1 region indicates that a pathological process is sustained in the area after the reperfusion phase and this may be of significance for ischemic brain injury. PMID- 7798924 TI - Time-related cortical amino acid changes after basal forebrain lesion: a microdialysis study. AB - Cholinergic basal forebrain (BF) lesions in experimental animals have been used as a potential model for cholinergic deficits in cortex and hippocampus that occur in normal aging and Alzheimer's disease (AD). Glutamatergic cortical neurons are also affected in AD and could be part of the neurodegenerative process. In the present study, the effect of bilateral BF lesion with ibotenic acid microinjection on cortical extracellular amino acid levels was determined. Samples were collected every 20 min with microdialysis probes in awake, freely moving rats under basal and potassium stimulation conditions and measured by HPLC with fluorescence detection. Microdialysis experiments were performed 13 days, 21 days, and 30 days after BF lesion. The effectiveness of the lesion was shown by a significant 30% depletion in acetyl-CoA:choline O-acetyltransferase (EC 2.3.1.6) activity in the frontal cortex. Under basal conditions at 13 days only extracellular levels of taurine (Tau) and Glu were significantly reduced. Tau and Glu levels were recovered after 21 days and 30 days, respectively. In contrast, increase in Gly levels reaches its significance only at 30 days after lesion. Significant increases of Gln levels were observed at 21 days and 30 days. Asp and Ser levels remained constant throughout the period studied. Potassium stimulation led to increased Asp, Glu, Gly, and Tau levels, whereas Gln content decreased and Ser remained unaltered. As Ser is not believed to be a neurotransmitter, its lack of variation in any of the experimental conditions studied supports specific neuronal changes of the other amino acids. Results are discussed with reference to data observed in AD patients and possible mechanisms underlying the changes are suggested. PMID- 7798925 TI - Comparison of postasphyxial resuscitation with 100% and 21% oxygen on cortical oxygen pressure and striatal dopamine metabolism in newborn piglets. AB - The present study tests the hypothesis that ventilation with 100% O2 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21% oxygen. This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model. Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extra cellular levels of dopamine and its metabolites by in vivo microdialysis. After establishment of a baseline, both the fraction of inspired oxygen (FiO2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period. For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen. It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls. During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21% oxygen (19 vs. 11 torr). During the first hour of reoxygenation, extracellular dopamine levels decreased to approximately 200% of control in the 21% oxygen group, whereas these levels were still much higher in the 100% oxygen group (approximately 500% of control). After approximately 2 h of reoxygenation, there was a secondary increase in extracellular dopamine to approximately 750 and approximately 3,000% of baseline for the animals ventilated with 21 and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798927 TI - Iron levels modulate alpha-secretase cleavage of amyloid precursor protein. AB - The amyloid precursor protein (APP) is a membrane-spanning glycoprotein that is the source of beta A4 peptides, which aggregate in Alzheimer's disease to form senile plaques. APP is cleaved within the beta A4 sequence to release a soluble N terminal derivative (APPsol), which has a wide range of trophic and protective functions. In the current study we have examined the hypothesis that iron availability may modulate expression or processing of APP, whose mRNA contains, based on sequence homology, a putative iron response element (IRE). Radiolabeled APP and its catabolites were precipitated from lysates and conditioned medium of stably transfected HEK 293 cells using antibodies selective for C-terminal, beta A4, and N-terminal domains. The relative abundance of the different APP catabolites under different conditions of iron availability was determined by quantitative densitometry after separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The data show a specific effect on the production of APPsol. Using standard conditions previously established for IRE studies, it was found that iron chelation reduces APPsol production, whereas iron level elevation augments it. No changes were observed in levels of immature and mature APP holoprotein or in the C-terminal alpha-secretase derivative C83, beta A4, and p3 peptides. The specificity for modulatory changes in APPsol suggests that iron acts at the level of alpha-secretase activity. In addition to its modulatory effects, iron at very high levels was found to inhibit maturation of APP and production of its downstream catabolites without blocking formation of immature APP. The data establish a potential physiological role for iron in controlling the processing of APP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798926 TI - Structural characterization by affinity cross-linking of glucagon-like peptide 1(7-36)amide receptor in rat brain. AB - Specific binding of glucagon-like peptide (GLP)-1(7-36)amide was detected in several rat brain areas, with the highest values being found in hypothalamic nuclei and the nucleus of the solitary tract. In hypothalamus and brainstem homogenate binding of 125I-GLP-1(7-36)amide was time, temperature, and protein content dependent and was inhibited by unlabeled proglucagon-derived peptides. The rank order of potency was GLP-1(7-36)amide >> GLP-1(1-36)amide > GLP-1(1-37) approximately equal to GLP-2 > glucagon. Scatchard analysis of the steady-state binding data was consistent with the presence of both high- and low-affinity binding sites in hypothalamus and brainstem. Brain 125I-GLP-1(7-36)amide-binding protein complexes were covalently cross-linked using disuccinimidyl suberate and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A single radiolabeled band of M(r) 56,000 identified in both hypothalamus and brainstem homogenates was unaffected by reducing agents. An excess of unlabeled GLP-1(7 36)amide abolished the band labeling, whereas glucagon had no effect. Other unlabeled GLPs inhibited M(r) 56,000 complex labeling with the following order of potency: GLP-1(1-36)amide > GLP-1(1-37) > GLP-2. The binding of 125I-GLP-1(7 36)amide and the intensity of the cross-linked band were similarly inhibited in a dose-response manner by increasing concentrations of unlabeled GLP-1(7-36)amide. Covalent M(r) 56,000 125I-GLP-1(7-36)amide-binding protein complexes solubilized by Triton X-100 were adsorbed onto wheat germ agglutinin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798928 TI - Evaluation of potential effectors of agonal glycolytic rate in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy. AB - Previously we have shown that hypercarbia produces a larger decrease in agonal glycolytic rate in 1-month-old swine than in newborns. In an effort to understand the mechanism responsible for this difference, we tested the hypothesis that hypercarbia produces age-related changes in the concentration of one or more effectors of phosphofructokinase activity. Specifically, in vivo 31P and 1H NMR spectroscopy was used to compare changes in lactate levels, intracellular pH, free magnesium concentration, and content of phosphorylated metabolites for these two age groups at three intervals during the first 1.5 min of complete ischemia in the presence or absence of hypercarbia (PaCO2 = 102-106 mm Hg). Hypercarbia produced the same drop in intracellular brain pH for both age groups, but the decrease in phosphocreatine level and increase in inorganic phosphate content were greater in 1-month-olds compared with newborns. During ischemia there was no difference between the magnitude of change in intracellular pH and levels of phosphocreatine and inorganic phosphate in hypercarbic 1-month-olds versus newborns. Under control conditions, i.e., normocarbia and normoxia, the free Mg2+ concentration was lower and the fraction of magnesium-free ATP was higher for newborns than 1-month-olds. However, there was no change in these variables for either age group during hypercarbia and early during ischemia. Thus, age-related differences in the relative decrease in agonal glycolytic rate during hypercarbia could not be explained by differences in intracellular pH, inorganic phosphate content, or free magnesium concentration. The [ADP]free at control was higher in newborns compared with 1-month-olds, and there was no age-related difference in [AMP]free. These variables did not change for newborns when exposed to hypercarbia, but for 1-month-olds [ADP]free and [AMP]free increased during hypercarbia relative to control values. High-energy phosphate utilization during ischemia for hypercarbic 1-month-olds was reduced by 74% compared with normocarbic 1-month-olds during ischemia, whereas the reduction in energy utilization (14%) was not significant for hypercarbic versus normocarbic newborns during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7798929 TI - Production of polyclonal antisera that recognize and distinguish between the extracellular domains of neuronal nicotinic acetylcholine receptor subunits. AB - Ligand-gated ion channels are oligomeric transmembrane proteins that usually contain more than one kind of monomer. The variety of monomers available to participate in oligomer formation and the apparent latitude in acceptable monomer combinations allows considerable diversity. Mechanisms for identifying the monomers comprising specific receptors are needed. We have generated affinity purified polyclonal antisera that recognize the extracellular domain of nine neuronal nicotinic acetylcholine receptor (nAChR) subunits and distinguish between them. We prepared these antisera by immunizing rabbits with bacterially expressed recombinant protein representing the N-terminal extracellular domain of each neuronal nAChR subunit followed by affinity purification of antibodies against synthetic peptides corresponding to residues 68-81 of the alpha 1 subunit. We demonstrate subunit specificity of each affinity-purified antisera by western blots of the bacterially expressed protein and immunoblot against peptide. We further used these antibodies to demonstrate expression of neuronal nAChR subunits on the surface of transiently transfected simian kidney (COS-7) cells. PMID- 7798932 TI - Two stages in neurite formation distinguished by differences in tubulin metabolism. AB - Changes in tubulin solubility during neurite formation were studied biochemically using rat dorsal root ganglion neurons in culture. When fractionated with Ca(2+) containing buffer at low temperature, a considerable proportion of total cellular tubulin was recovered in the insoluble fraction. We designated this cold/Ca(2+) insoluble tubulin (InsT) and distinguished it from cold/Ca(2+)-soluble tubulin (SoIT). From the relative amount of InsT, neurite formation was found to proceed through two distinct stages. The first 6 days after plating (stage 1) in which the proportion of InsT increased dramatically (from 5 to 60%) coincided with neurite outgrowth. In the following period (stage 2), a constant level of InsT was maintained, whereas neurite maturation took place. Pulse-labeling experiments further revealed that the two stages differed significantly in terms of tubulin metabolism. High rates of synthesis as well as conversion from SoIT to InsT were observed in stage 1, whereas stage 2 was characterized by a decrease in both of these rates and an increase in the rate of degradation. The results show for the first time the coordinated changes in tubulin metabolism that underlie the process of neurite formation. PMID- 7798930 TI - Molecular cloning of a novel G protein-coupled receptor related to the opiate receptor family. AB - A cDNA clone encoding a novel G protein-linked receptor was isolated from a rat cerebral cortex cDNA library using a polymerase chain reaction-amplified cDNA fragment as a probe. This 2.4-kb clone encodes a 367 amino acid protein with seven putative transmembrane spanning domains. The protein is highly homologous to the cloned micro, delta, and kappa opioid receptors and shares with them structural features such as three glycosylation sites in the amino terminus, a cyclic AMP-dependent kinase phosphorylation site in the third cytoplasmic loop, an aspartic acid residue in the second transmembrane domain, and a palmitoylation site on the intracellular carboxy terminus. The receptor is also homologous with members of the somatostatin receptor family, yet it binds neither opiate nor somatostatin ligands. Northern blot analysis reveals two transcripts of 3.2 and 7.6 kb that are predominantly expressed in the cerebral cortex and hypothalamus. In situ hybridization analysis also shows a high abundance of mRNA in the cerebral cortex, hippocampus, amygdala, hypothalamus, thalamus, and dorsal raphe nuclei. It is suggested that the endogenous ligand for this receptor may represent a novel neuropeptide that may be closely related to the opiate peptide family. PMID- 7798931 TI - Rat brain protein phosphatase 2A: an enzyme that may regulate autophosphorylated protein kinases. AB - Protein phosphatase 2A (PP2A) isolated from whole rat brain homogenate supernatants has been compared with that extracted from rat synaptosomal membranes. Both purified enzymes are comprised of the three known PP2A polypeptide chains of 65 (A subunit), 55 (B/B' subunit), and 38 (C subunit) kDa and have okadaic acid inhibition curves (Ki = 0.05 nM) nearly identical to that reported for skeletal muscle PP2A. The isolated 38-kDa subunit of rat brain PP2A appears to contain phosphotyrosine based on cross-reactivity with a specific monoclonal antibody (PY-20). Amino acid compositions and sequences of peptides isolated from the 65- and 38-kDa species correspond to regions of the cDNA deduced sequences of the regulatory and catalytic subunits of protein phosphatase 2A from several sources. Studies reported here also demonstrate that autophosphorylated protein kinases, particularly Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), are excellent substrates for brain PP2A. Furthermore, Ca(2+)-dependent K(+)-depolarization of hippocampal synaptosomes was accompanied by a sequential increase, then decrease, in CaM kinase II phosphorylation level over a 45-s time course. The decrease was blocked by 1 nM okadaic acid. These data demonstrate that the type 2A protein phosphatase is present at the synapses of CNS neurons where its localization could alter the functions of phosphoproteins involved in synaptic plasticity. PMID- 7798933 TI - Fatty acyl-CoA inhibits 1-alkyl-sn-glycero-3-phosphate acetyltransferase in microsomes of immature rabbit cerebral cortex: control of the first committed step in the de novo pathway of platelet-activating factor synthesis. AB - Microsomal fractions of cerebral cortices of 15-day-old rabbits were used to study the 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase that generates 1 alkyl-2-acetyl-sn-glycero-3-phosphate in the de novo path of platelet-activating factor synthesis. The AGP acetyltransferase activity was inhibited by small concentrations of medium-long chain fatty acyl-CoA thioesters. In contrast, the AGP acyltransferase used oleoyl-CoA as substrate and was not inhibited by the presence of acetyl-CoA in high molar excess. The inhibition of AGP acetyltransferase was seen at concentrations of oleoyl-CoA as low as 0.5 microM using 12.5 microM AGP and 200 microM acetyl-CoA. The inhibition by oleoyl-CoA was noncompetitive for the acetyl-CoA substrate. However, there was evidence that the oleoyl-CoA was competing with AGP in the acetyltransferase reaction, as the inhibition was lessened by increasing the AGP substrate concentration. Several acyl-CoA thioesters were effective as inhibitors of the AGP acetyltransferase, including oleoyl-, palmitoyl-, lauroyl-, and octanoyl-CoA. Propionyl- and butyryl CoA were less effective as inhibitors, and propionyl-CoA was found to be a competitive inhibitor for acetyl-CoA. We have noted earlier that MgATP is an effective inhibitor of the AGP acetyltransferase and here we show that the inhibition by oleoyl-CoA can be increased by the presence of 0.1 mM MgATP. In brain ischemia, a decline in ATP levels would likely lead to a corresponding fall in acyl-CoA concentrations, thereby relieving the inhibition of AGP acetyltransferase and permitting the flow of AGP into the de novo pathway of platelet-activating factor synthesis. PMID- 7798934 TI - Production and characterization of monoclonal antibodies to bovine brain succinic semialdehyde reductase. AB - Monoclonal antibodies against bovine brain succinic semialdehyde reductase were produced and characterized. A total of nine monoclonal antibodies recognizing different epitopes of the enzyme were obtained, of which two inhibited the enzyme activity and three stained cytosol of rat spinal cord neurons as observed by indirect immunofluorescence microscopy. When unfractionated total proteins of bovine brain homogenate were separated by gel electrophoresis and immunoblotted, the antibodies specifically recognized a single protein band of 34 kDa, which comigrates with purified bovine succinic semialdehyde reductase. Using the antisuccinic semialdehyde reductase antibodies as probes, we investigated the cross-reactivities of brain succinic semialdehyde reductases from some mammalian and an avian species. The immunoreactive bands on western blots appeared to be the same in molecular mass--34 kDa--in all animal species tested, including humans. The result indicates that brain succinic semialdehyde reductase is distinct from other aldehyde reductases and that mammalian brains contain only one succinic semialdehyde reductase. Moreover, the enzymes among the species are immunologically very similar, although some properties of the enzymes reported previously were different from one another. PMID- 7798935 TI - Effect of cytidine on membrane phospholipid synthesis in rat striatal slices. AB - Using rat striatal slices, we examined the effect of cytidine on the conversion of [3H]choline to [3H]-phosphatidylcholine ([3H]PC), and on net syntheses of PC, phosphatidylethanolamine (PE), and phosphatidylserine, when media did or did not also contain choline, ethanolamine, or serine. Incubation of striatal slices with cytidine (50-500 microM) caused dose-dependent increases in intracellular cytidine and cytidine triphosphate (CTP) levels and in the rate of incorporation of [3H] choline into membrane [3H]PC. In pulse-chase experiments, cytidine (200 microM) also increased significantly the conversion of [3H]choline to [3H]PC during the chase period. When slices were incubated with this concentration of cytidine for 1 h, small (7%) but significant elevations were observed in the absolute contents (nmol/mg of protein) of membrane PC and PE (p < 0.05), but not phosphatidylserine, the synthesis of which is independent of cytidine-containing CTP. Concurrent exposure to cytidine (200 microM) and choline (10 microM) caused an additional significant increase (p < 0.05) in tissue PC levels beyond that produced by cytidine alone. Exposure to choline alone at a higher concentration (40 microM) increased the levels of all three membrane phospholipids (p < 0.01); the addition of cytidine, however, did not cause further increases. Concurrent exposure to cytidine (200 microM) and ethanolamine (20 microM) also caused significantly greater elevations (p < 0.05) in tissue PE levels than those caused by cytidine alone. In contrast, the addition of serine (500 microM) did not enhance cytidine's effects on any membrane phospholipid. Exposure to serine alone, however, like exposure to sufficient choline, increased levels of all three membrane phospholipids significantly (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798936 TI - Characterization of sialyltransferase-IV activity and its involvement in the c pathway of brain ganglioside metabolism. AB - To characterize the sialyltransferase-IV activity in brain tissues, the activities of GM1b-, GD1a-, GT1b-, and GQ1c-synthases in adult cichlid fish and rat brains were examined using GA1, GM1, GD1b, or a cod brain ganglioside mixture as the substrate. The GD1a-synthase activity in the total membrane fraction from cichlid fish brain required divalent cations such as Mg2+ or Mn2+ and Triton CF 54 for its full activity. The Vmax value was 1,340 pmol/mg of protein/h at an optimal pH of 6.5, whereas the apparent Km values for CMP-sialic acid and GM1 were 172 and 78 microM, respectively. Cichlid fish and rat brains also contained GM1b-, GT1b-, and GQ1c-synthase activities. The ratio of GM1b-, GD1a-, and GT1b synthase activities in fish brain was 1.00:0.89:1.13, respectively, and in rat brain 1.00:0.60:0.63. Incubation of fish brain membranes with a cod brain ganglioside mixture, which contains GT1c, and [3H]CMP-sialic acid produced radiolabeled GQ1c. It is interesting that the adult rat brain also contains an appreciable level of GQ1c-synthase activity despite its very low concentrations of c-series gangliosides. The GD1a- or GQ1c-synthase activity in fish and rat brain was inhibited specifically by coincubation with the glycolipids that serve as the substrates for other sialyltransferase-IV reactions. Thus, the GD1a synthase activity was inhibited by GA1 and GD1b, but not by LacCer, GM3, or GD3. In a similar manner, the synthesis of GQ1c was suppressed by GA1, GM1, and GD1b, but not by LacCer, GM3, or GD3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798937 TI - Coupling of corticotropin-releasing hormone receptors to adenylyl cyclase in human Y-79 retinoblastoma cells. AB - In human Y-79 retinoblastoma cells, corticotropin-releasing hormone (CRH) stimulates adenylyl cyclase activity and increases cyclic AMP accumulation. Different CRH analogues mimic the CRH stimulation of adenylyl cyclase and show similar sensitivity to the CRH receptor antagonist alpha-helical CRH9-41. Vasoactive intestinal peptide (VIP) also increases the enzyme activity but less potently than CRH, and its effect is counteracted by the VIP receptor antagonist [D-p-Cl-Phe6,Leu17]VIP. The VIP antagonist does not affect the response to CRH. The CRH-stimulated adenylyl cyclase activity is amplified by Mg2+, is inhibited by submicromolar concentrations of Ca2+, and requires GTP. Moreover, the CRH stimulation is reduced by pretreatment of cells with cholera toxin and by incubation of membranes with the RM/1 antibody, which recognizes the C-terminus of the alpha subunit of Gs. In immunoblots, the RM/1 antibody identifies a doublet of 45 and 52 kDa. Two proteins of similar molecular weights are ADP ribosylated by cholera toxin. These data demonstrate that in human Y-79 retinoblastoma cells, specific CRH receptors stimulate cyclic AMP formation by interacting with Gs and by affecting a Ca(2+)-inhibitable form of adenylyl cyclase. PMID- 7798938 TI - Human Y-79 retinoblastoma cells exhibit specific corticotropin-releasing hormone binding sites. AB - In this study we have identified specific binding sites for corticotropin releasing hormone (CRH) in human Y-79 retinoblastoma cell membranes by using 125I Tyr-ovine CRH (125I-oCRH) as radioligand. Binding at 19 degrees C was rapid with steady state being reached within 20 min, reversible and linear with membrane protein concentration. The 125I-oCRH binding was enhanced by Mg2+ and inhibited by the GTP analogue guanosine 5'-O-(3'-thiotriphosphate). Y-79 cell membranes exhibited two populations of binding sites, a high-affinity site with an apparent dissociation constant (KD) of 1 nM and a low-affinity site with an apparent KD of 500 nM. 125I-oCRH binding was completely antagonized by human/rat CRH, [Met(O)21]oCRH, alpha-helical CRH9-41, urotensin I, and sauvagine with a rank order of potency similar to that displayed by CRH receptors of other tissues. These data describe for the first time the presence of specific CRH-binding sites in retinal cells. The Y-79 cell line may therefore constitute a valuable model in which to study CRH action on retinal cells. PMID- 7798939 TI - Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice. AB - Apolipoproteins have been implicated in the salvage and reutilization of myelin cholesterol during Wallerian degeneration and the subsequent nerve regeneration. Current evidence suggests that myelin cholesterol complexes with apolipoproteins E and A-I to form lipoproteins that are taken up via low-density lipoprotein receptors on myelinating Schwann cells. We recently reported, however, that apolipoprotein E is not required for nerve regeneration or reutilization of myelin cholesterol. We have now investigated nerve regeneration and the reutilization of cholesterol in mutant mice deficient in both apolipoproteins E and A-I. Morphologic examination of nerves 4 and 12 weeks after crush injury revealed that regeneration proceeded at a normal rate in the absence of these apolipoproteins. Autoradiography of regenerating nerves indicated that prelabeled myelin lipid was reutilized in the regenerating myelin. 3-Hydroxy-3 methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, was down-regulated in the regenerating nerves, indicative of cholesterol uptake via lipoproteins. Prelabeled myelin cholesterol was present in lipoprotein fractions isolated from crushed nerves of mutant mice. These data suggest that there is considerable redundancy in the process of cholesterol reutilization within nerve, and that apolipoproteins other than apolipoproteins E and A-I may be involved in the recycling of myelin cholesterol. PMID- 7798940 TI - Beta 2-adrenoreceptors stimulate c-fos transcription through multiple cyclic AMP- and Ca(2+)-responsive elements in cerebellar granular neurons. AB - Neurons from the granular layer of the cerebellum express functional beta 2 adrenoreceptors (beta 2-ARs). We show that stimulation of beta 2-ARs with isoprenaline increases cyclic AMP (cAMP) production and stimulates transcription of genes containing the cAMP-responsive element (CRE; TGACGTCA). This effect is mediated by cAMP-dependent protein kinase and the trans-acting factor CRE binding protein. Transcriptional regulation by the beta 2-AR was investigated by using the c-fos protooncogene as a model system. We show that beta 2-ARs stimulate c fos mRNA accumulation, increase AP1 binding activity, and stimulate transcription through the phorbol ester-responsive element (TGACTCA). The transcriptional regulation of c-fos itself was studied with reporter constructs driven by c-fos promoter sequences. Deletion studies revealed that beta 2-ARs stimulate c-fos transcription through at least three distinct regulatory sequences: (a) the CRE located at -60 bp 5' to the initiation site, (b) the fos AP1-like element (-291 to -297), and (c) the serum-responsive element (-297 to -317). The regulation of these elements by the two putative second messengers of the beta 2-AR, cAMP and Ca2+, was analyzed. We report that all three of these regulatory sequences are coregulated by both second messengers. These results indicate that beta 2-ARs stimulate c-fos transcription by multiple cAMP- and Ca(2+)-dependent regulatory elements in neurons. PMID- 7798942 TI - Lipid composition of neuronal cell bodies and neurites from cultured dorsal root ganglia. AB - The lipid composition of neuronal somata and neuritic processes of cultured root ganglia has been determined. Neuronal soma contained 37% of dry weight as lipid (15.4% cholesterol, 4.8% galactolipid, and 57.1% phospholipid). The major phospholipids were phosphatidylcholine and phosphatidyl ethanolamine. Galactolipids consisted of cerebroside and sulfatide in molar ratio 2:1. The neuronal soma contained tetrasialo-, disialo-, and monosialoganglioside. In contrast, neurites contained 15% of the dry weight as lipid (22.1% cholesterol, 7.7% galactolipid with cerebroside and sulfatide in molar ratio 2:1, and 56.4% total phospholipid). The neuritic galactolipid content was higher, as was the percentage of sphingomyelin, and phosphatidyl serine. The higher cholesterol content in neuritic lipid reflected the higher percentage of plasma membrane in this compartment. The ganglioside pattern of neurites was distinct from that of the neuronal soma and consisted entirely of gangliosides GQ1b, GT1b, GD1b, GD1a, and GD3, with no monosialogangliosides. The results indicate a preferential phospholipid and glycolipid sorting to the neuritic plasma membrane that may be related to the distinctive functions of this neuronal compartment. PMID- 7798941 TI - Glucose metabolism in the developing cerebral cortex as detected by 1H(13C) nuclear magnetic resonance spectroscopy ex vivo. AB - Metabolism of [1-13C]glucose was monitored in superfused cerebral cortex slice preparations from 1-, 2-, and 5-week-old rats using 1H-observed/13C-edited (1H(13C)) NMR spectroscopy. The rate of label incorporation into glutamate C-4 did not differ among the three age groups: 0.52-0.67% of total 1H NMR-detected glutamate/min. This was rather unexpected, as oxygen uptake proceeded at 1.1 +/- 0.1, 1.9 +/- 0.1, and 2.0 +/- 0.1 mumol/min/g wet weight in brain slices prepared from 1-, 2-, and 5-week-old animals, respectively. Steady-state glutamate C-4 fractional enrichments in the slice preparations were approximately 23% in all age groups. In the acid extracts of slices glutamate C-4 enrichments were smaller, however, in 1- and 2-week-old (17.8 +/- 1.7 and 16.8 +/- 0.8%, respectively) than in 5-week-old rats (22.7 +/- 0.7%) after 75 min of incubation with 5 mM [1-13C]glucose. We add a new assignment to the 1H(13C) NMR spectroscopy, as acetate C-2 was detected in slice preparations from 5-week-old animals. In the acid extracts of slice preparations acetate C-2 was labeled by approximately 30% in 5-week-old rats but by 15% in both 1- and 2-week-old animals, showing that the turnover rate was increased in 5-week-old animals. In the extracts 3-4% of the C-6 of N-acetyl-aspartate (NAA; CH3 of the acetyl group) contained label as determined by both NMR and mass spectrometry, which indicated that there was no significant labeling to other carbons in NAA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798943 TI - Aspartate aminotransferase and glutamate dehydrogenase activities in the squid giant nerve. AB - The present study sought to investigate the presence and distribution of some enzymatic activities involved in the metabolism of glutamate in the giant nerve fiber of the tropical squid Sepioteuthis sepioidea. Specific activities of aspartate aminotransferase and glutamate dehydrogenase were evaluated in homogenates of the isolated giant fiber, extruded axoplasm, and axoplasm-free giant nerve fiber sheaths. The activities of both enzymes were present in the tissue. The specific activity of aspartate aminotransferase was similar in axoplasm and sheaths. However, the specific activity of glutamate dehydrogenase was an order of magnitude higher in the sheaths. This finding is discussed in the framework of the hypothesis that proposes that a differential distribution of the enzymes of the glutamatergic system between the axonal and neuroglial compartments forms part of a system of communication between these cells whose neuronal signal may be glutamate. PMID- 7798944 TI - Elevated levels of the endosomal-lysosomal proteinase cathepsin D in cerebrospinal fluid in Alzheimer disease. AB - Lysosomal hydrolases are normally intracellular enzymes but are abundant extracellularly within senile plaques in Alzheimer disease and in other conditions where beta-amyloid accumulates. To examine whether acid hydrolases released from abnormal hydrolase-laden neurons are detectable in CSF, we measured levels of the major aspartic proteinase of lysosomes, cathepsin D (Cat D), in ventricular CSF collected after death from 30 patients with Alzheimer disease, 14 patients with Huntington disease, and seven patients with other neurodegenerative diseases. The levels of Cat D-immunoreactive protein, expressed as micrograms per milliliter of protein, determined by western blot immunoassay using a polyclonal antiserum against human brain Cat D, were more than fourfold higher in the Alzheimer patients than in the other patient groups (p < 0.0005). Cat D activity, assayed separately against [14C]methemoglobin at pH 3.2, was also significantly elevated but less than Cat D content. The lower specific activity of Cat D in Alzheimer CSF therefore indicated that the abnormally accumulated Cat D included a high proportion of inactive enzyme. These results indicate that abnormal Cat D release from affected neurons into the extracellular space is an active, ongoing process in Alzheimer brain. In addition, the levels of this enzyme and possibly other lysosomal hydrolases in CSF may prove to be useful biological markers of Alzheimer disease. PMID- 7798945 TI - The degradative pathway of gangliosides GM1 and GM2 in Neuro2a cells by sialidase. AB - Gangliosides GM1 [3H-labeled at the sphingosine (Sph) moiety] and GM2 [3H-labeled at the Sph or N-acetylgalactosamine (GalNAc) moiety] were administered to cultured Neuro2a cells for varying pulse (1-4 h) and chase (up to 4 h) periods, and their metabolic processing was followed. The main and earliest formed 3H metabolites of [Sph-3H]GM1 were GM2, asialo-GM1 asialo-GM2, and lactose-ceramide, and those of [Sph-3H]GM2 were asialo-GM2 and lactose-ceramide. The asialo-GM1 and asialo-GM2 formed were isolated and chemically characterized. [3H]Asialo-GM2 was produced in identical amounts after treatment with equimolar [Sph-3H]GM2 and [GalNAc-3H]GM2. At low temperature or in the presence of chloroquine, the formation of all 3H-metabolites, including asialo-GM2 and asialo-GM1, was undetectable, indicating that ganglioside metabolic processing was an endocytosis and lysosome-dependent process. These results demonstrate that in Neuro2a cells exogenous GM1 (and GM2) is mainly degraded through the pathway GM1-->GM2-->asialo GM2-->-->Sph, with a minor fraction of GM1 undergoing degradation with the sequence GM1-->asialo-GM-1-->asialo-GM2-->-->Sph. These findings are consistent with the hypothesis that Neuro2a cells contain a sialidase (likely of lysosomal nature) affecting ganglioside GM1 and GM2. The sialidase-mediated degradative pathway of GM1 and GM2 in Neuro2a cells might be related to the tumoral nature of these cells. PMID- 7798946 TI - NMDA receptor involvement in toxicity to dopamine neurons in vitro caused by the succinate dehydrogenase inhibitor 3-nitropropionic acid. AB - Exposure of mesencephalic dopamine neurons to an irreversible inhibitor of succinate dehydrogenase (SDH), 3-nitropropionic acid (3-NPA), for 24 h on day 12 in vitro, produced a dose-dependent loss of high-affinity dopamine uptake when measured 48 h following 3-NPA removal. ATP concentrations in the cultures were reduced by 57% after 3 h of treatment with the highest concentration of 3-NPA tested (500 microM). To determine whether glutamate receptors mediated the dopamine toxicity by 3-NPA, cultures were examined for their sensitivity to excitatory amino acid-induced toxicity. Mesencephalic cultures exposed to either 100 microM NMDA or kainate, on day 12 for 24 h, showed complete loss of dopamine uptake following 48 h of recovery. The NMDA and non-NMDA antagonists, MK-801 (1 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 15 microM), completely prevented the effects of NMDA or kainate, respectively, when present at the time of toxin exposure. In cultures treated with 3-NPA, MK-801, but not CNQX, significantly attenuated the loss of dopamine uptake. Direct measurement of the effect of 3-NPA on SDH activity showed that 3-NPA dose-dependently inhibited SDH in vitro in a manner commensurate with the loss of dopamine uptake by 3-NPA. MK 801 had no effect on basal SDH activity or on 3-NPA inhibition of SDH. These data are consistent with the interpretation that metabolic inhibition in dopamine neurons can trigger a secondary excitotoxicity that is mediated by NMDA receptors. PMID- 7798947 TI - Proadrenomedullin N-terminal 20 peptide (PAMP), an endogenous anticholinergic peptide: its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla. AB - In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca(2+)-dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 microM) and catecholamines (EC50 = 63.0 microM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP [1-20]NH2 inhibited carbachol-induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 microM in a noncompetitive manner and thereby reduced carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 microM) and catecholamine secretion (IC50 = 1.6 microM). It did not alter high K(+)-induced 45Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca(2+)-dependent exocytosis in response to nicotinic receptor stimulation. PMID- 7798948 TI - Down-regulation of AMPA receptor subunit GluR2 in amygdaloid kindling. AB - Alterations in glutamatergic transmission are postulated to be important in kindling and epilepsy. The levels of alpha-amino-3-hydroxy- 5-methylisoxazole-4 propionic acid (AMPA) receptor subunits (GluR1, 2, and 4) were compared in amygdala-kindled and sham-operated animals using subunit-specific antibodies and quantitative western blotting. Four limbic regions were examined: limbic forebrain, piriform cortex/amygdala, hippocampus, and entorhinal cortex. When subunit levels were examined 24 h after the last stage 5 seizure, levels of GluR2 were found to be selectively reduced in limbic forebrain (30%) and piriform cortex/amygdala (25%), with no changes in other regions examined. In addition, no changes in the other subunits were observed in any region. The decrease in GluR2 that was observed in kindled animals at 24 h was no longer present at 1 week and 1 month after the last stage 5 seizure. Because the GluR2 subunit uniquely determines the calcium permeability of these receptors and because the piriform cortex has been implicated as a source of excitatory drive for limbic seizures, reduced GluR2 expression may be important in increasing neuronal excitability in kindling-induced epilepsy, or may reflect a compensatory mechanism resulting from kindling. PMID- 7798949 TI - A function for butyrylcholinesterase? PMID- 7798950 TI - A negative regulatory element in the rat dopamine beta-hydroxylase gene contributes to the cell type specificity of expression. AB - Dopamine beta-hydroxylase (DBH) catalyzes the synthesis of the neurohormone norepinephrine and is expressed only in noradrenergic and adrenergic cells of the nervous and endocrine systems. We have previously described a positive-acting genetic regulatory element of the DBH that contributes to the restricted expression of this gene. In the study described here, we identify and characterize a negative-acting regulatory element within the 5'-flanking region of the rat DBH gene. This negative regulatory element, which is located between 282 and -232, represses transcription from the DBH promoter in cell lines of noncatecholaminergic origin and binds to nuclear factors found in extracts from both the catecholaminergic cell line SHSY-5Y and the noncatecholaminergic cell lines JEG-3 and C6. The negative regulatory region will reduce transcription from a heterologous promoter in two noncatecholaminergic cell lines. These experiments demonstrate that the selective expression of the DBH gene is controlled by both positive- and negative-acting genetic regulatory elements. PMID- 7798951 TI - Ca(2+)- and nitric oxide-dependent stimulation of cyclic GMP synthesis in neuronal cell line induced by P2-purinergic/pyrimidinergic receptor. AB - The mechanism by which cyclic GMP synthesis is activated through a nucleotide receptor was studied in mouse neuroblastoma x rat glioma hybrid cells [108CC15 (NG 108-15)]. The transient increase in cyclic GMP level induced by ATP reached its maximum at 20 s and lasted for approximately 1 min. The maximal rise in cyclic GMP level achieved was highest for ATP and decreased in the following order: ATP = adenosine 5'(gamma-thio)triphosphate > UTP = 2-methylthio-ATP > ADP much greater than CTP, AMP, alpha,beta-methylene-ATP, 2'- and 3'-O-(4 benzoylbenzoyl)ATP. The EC50 of 1 +/- 0.2 microM for UTP was significantly lower than that for ATP (14 +/- 8 microM) and for all the other nucleotides tested. The rank order of potency is consistent with the pharmacology of a P2u receptor. At submaximal concentrations of the nucleotides ATP and UTP, the rise in cyclic GMP level was inhibited by suramin (IC50 = 40-60 microM) or the pyridoxal phosphate analogue pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (IC50 = 20-30 microM). Pretreatment of cells with the Ca2+ ionophore ionomycin or with 2,5 di(tert-butyl)-1,4-benzohydroquinone, an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, a maneuver to deplete internal Ca2+ stores, suppressed the ATP- or UTP-induced stimulation of cyclic GMP synthesis. Similarly, loading of the cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N' tetraacetic acid inhibited cyclic GMP formation by ATP. Preincubation with forskolin to raise the cyclic AMP level potentiated the ATP-induced rise in cyclic GMP level by 60%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7798952 TI - A Ewing's sarcoma cell line showing some, but not all, of the traits of a cholinergic neuron. AB - The Ewing's sarcoma cell line ICB 112 was examined in detail for a cholinergic phenotype. Choline acetyltransferase activity (12.3 +/- 2.9 nmol/h/mg of protein) was associated with the presence of multiple mRNA species labeled with a human choline acetyltransferase riboprobe. Choline was taken up by the cells by a high affinity, hemicholinium-3-sensitive transporter that was partially inhibited when lithium replaced sodium in the incubation medium; the choline taken up was quickly incorporated into both acetylcholine and phosphorylcholine. High-affinity binding sites for vesamicol, an inhibitor of vesicular acetylcholine transport, were also present. The mRNAs for synaptotagmin (p65) and the 15-kDa proteolipid were readily detected and were identical in size to those observed in cholinergic regions of the human brain. Cumulative acetylcholine efflux was increased by raising the extracellular potassium level or the addition of a calcium ionophore, but the time course of stimulated efflux was slow and persistent. These results show that this morphologically undifferentiated cell line is capable of acetylcholine synthesis and expresses markers for synaptic vesicles as well as proteins implicated in calcium-dependent release but lacks an organized release mechanism. PMID- 7798954 TI - (+)-(S)-dihydroaeruginoic acid, an inhibitor of Septoria tritici and other phytopathogenic fungi and bacteria, produced by Pseudomonas fluorescens. AB - Three antibiotics were isolated from a CH2Cl2 extract of the liquid culture of Pseudomonas fluorescens strain PFM2. Two of the antibiotics were identified as 2,4-diacetylphloroglucinol and pyoluterin. The structure elucidation, absolute stereochemistry, synthesis, and biological activities of the new antibiotic (+) (S)- dihydroaeruginoic acid [1] are reported. PMID- 7798953 TI - 5'-(N-ethylcarboxamido)adenosine inhibits Ca2+ influx and activates a protein phosphatase in bovine adrenal chromaffin cells. AB - We investigated the effect of the adenosine receptor agonist 5'-(N ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4 phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30-40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 +/- 3.3%), slowly developing inhibition of [Ca2+]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells. PMID- 7798955 TI - Chemical and bioactive constituents from Zanthoxylum simulans. AB - Two new benzo[c]phenanthridine alkaloids, 6-methyldihydrochelerythrine [1] and 6 methylnorchelerythrine [2], together with 23 known compounds, were isolated from the root bark of Zanthoxylum simulans. Structures were elucidated by spectral analysis. Among them, the pyranoquinoline alkaloids, zanthosimuline [3], and huajiaosimuline [4], exhibited cytotoxic activity. In addition, compound 4 showed significant antiplatelet aggregation activity and induced terminal differentiation with cultured HL-60 cells. PMID- 7798957 TI - Four new dimeric peptide alkaloids, anchinopeptolides B-D, and cycloanchinopeptolide C, congeners of anchinopeptolide A, from the Mediterranean marine sponge Anchinoe tenacior. AB - Following the characterization of anchinopeptolide A[1], three new congeneric dimeric peptide alkaloids, named anchinopeptolides B [2], C[3], and D[4], have been isolated from the Mediterranean sponge Anchinoe tenacior. A fourth compound, cycloanchinopeptolide C[5], which is related to anchinopeptolide C[3] by a head to-head intramolecular [2+2] cyclo-addition reaction, has also been isolated. The structures of these peptide alkaloids have been elucidated on the basis of spectral evidence. Anchinopeptolides bind to the somatostatin, human B2 bradykinin, and neuropeptide Y receptors. PMID- 7798956 TI - Bioactive terpenoids from Octocorallia, I. Bioactive diterpenoids: litophynols A and B from the mucus of the soft coral Litophyton sp. AB - Two new eunicellin-type diterpenoids, litophynols A [1] and B [2], and the known diterpenoids litophynins E [3], H [11], and I monoacetate [12], were isolated from the mucus secreted by the soft coral Litophyton sp. Their structures have been elucidated on the basis of spectral and single crystal X-ray analyses. These compounds have hemolytic activity. PMID- 7798958 TI - Synthesis of quercetin-3-O-beta-D-glucopyranosyl-(1-->2)-beta-D- xylopyranoside via orthoester methodology. AB - The synthesis of quercetin-3-O-beta-D-glucopyranosyl-(1-->2)-beta-D xylopyranoside [10], a flavonoid recently isolated from Kalanchoe prolifera, has been carried out via orthoester methodology. PMID- 7798959 TI - Antibacterial triterpenoid acids from Dillenia papuana. AB - Three new oleanene-type triterpenoids, dillenic acids A [1], B [2], and C [3], and two known compounds, 3-oxoolean-1,12-dien-30-oic acid [4] (a new natural product) and the lupene derivative betulinaldehyde, have been isolated from the Papua New Guinean medicinal plant Dillenia papuana. The structures of the new compounds were elucidated as 2 alpha-hydroxy-3-oxoolean-12-en-30-oic acid, 2-oxo 3 beta-hydroxyolean-12-en-30-oic acid and 1 alpha-hydroxy-3-oxoolean-12-en-30-oic acid. The 1H- and 13C-nmr data of all new compounds were assigned unambiguously using a variety of 2D nmr experiments including 1H-1H-COSY, HMQC, HMBC, and NOESY experiments. Of these compounds, 1-4 showed antibacterial activities against Bacillus subtilis, Escherichia coli, and Micrococcus luteus. PMID- 7798960 TI - Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. AB - Bioassay-guided analysis of an EtOH extract of Moringa oleifera leaves showing hypotensive activity led to the isolation of two nitrile glycosides, niazirin [1] and niazirinin [2], and three mustard oil glycosides, 4-[(4'-O-acetyl-alpha-L rhamnosyloxy)benzyl]isothiocyanate [4], niaziminin A, and niaziminin B. Glycoside 2 is a new compound. Niaziminins A and B have previously been obtained from the left extract as a mixture, while compound 4 is new from this source. Structural determination was accomplished by means of spectroscopic methods including appropriate 2D nmr experiments and chemical reactions. This is the first report of the isolation of nitriles, an isothiocyanate, and thiocarbamates from the same plant species. Isothiocyanate 4 and the thiocarbamate glycosides niaziminin A and B showed hypotensive activity while nitrile glycosides 1 and 2 were found to be inactive in this regard. PMID- 7798961 TI - Insect antifeedant activity of clerodane diterpenoids. AB - Fourteen clerodane-type diterpenoids isolated from plants in the genera Baccharis, Teucrium, and Salvia were assayed for antifeedant activity against Tenebrio molitor larvae in order to establish structure-activity relationships. Among the compounds tested, furanoditerpenes with alpha, beta-unsaturated-gamma lactone moieties, or C-4-epoxy substitution with C-5-methylacetoxy or C-12 acyloxy functionalities, exhibited maximal antifeedant and repellent activities. PMID- 7798962 TI - Antiplatelet aggregation principles of Dendrobium loddigesii. AB - The MeOH extract of the stem of Dendrobium loddigesii was found to inhibit the aggregation of rabbit platelets induced by arachidonic acid and collagen. Two active compounds, moscatilin [1] and moscatin [2], were isolated. Moscatilin diacetate [3] also exhibited antiplatelet aggregation activity. PMID- 7798963 TI - Triterpenoid saponins from Bellis sylvestris, I. Structures of the major deacylsaponins. AB - Two major saponins from Bellis sylvestris have been isolated and their structures determined, mainly by high-field nmr spectroscopy. One of these [2] was identical with bellissaponin BS1 from Bellis perennis, while the second is a new triterpenoid saponin [1], named besysaponin C12, and identified as 3-O-alpha-L rhamnopyranosyl-2 beta,3 beta,16 alpha,23-tetrahydroxyolean-12-en-28-oic acid 28 O-beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->2)-beta-D- fucopyranoside. PMID- 7798964 TI - Cylindol A, a novel biphenyl ether with 5-lipoxygenase inhibitory activity, and a related compound from Imperata Cylindrica. AB - Cylindol A [1] and B [2], two novel substances, have been isolated from Imperata cylindrica, and their structures have been elucidated on the basis of their spectral data coupled with chemical evidence and total synthesis. Cylindol A [1] showed 5-lipoxygenase inhibitory activity. PMID- 7798965 TI - (+/-)-Gelliusines A and B, two diastereomeric brominated tris-indole alkaloids from a deep water new caledonian marine sponge (Gellius or Orina sp.). AB - Two new diastereomeric brominated tris-indole alkaloids occurring as enantiomeric pairs, (+/-)-gelliusines A [1] and B [2], have been isolated from a deep water New Caledonian sponge (Gellius or Orina sp.), whose crude extract exhibited cytotoxicity against KB cells. Their structures were elucidated by spectroscopic methods including one- and two-dimensional nmr spectroscopy. The major compound, (+/-) gelliusine A [1], which showed very weak cytotoxicity, proved to be active at the serotonin receptor. PMID- 7798966 TI - Nepheliosyne A, new C47 acetylenic acid from the Okinawan marine sponge Xestospongia sp. PMID- 7798967 TI - Two new flavones from Calliandra californica. AB - Two new flavones were isolated from the medicinal plant Calliandra californica, 7,2',4',5'-tetramethoxyflavone [1] and 5-hydroxy-7,2',4',5'-tetramethoxyflavone [2]. The structures were determined from spectral evidence and both compounds were synthesized. Compound 2 exhibited antimicrobial activity for two test bacterial strains. PMID- 7798968 TI - Binding of quinolizidine alkaloids to nicotinic and muscarinic acetylcholine receptors. AB - Fourteen quinolizidine alkaloids, isolated from Lupinus albus, L. mutabilis, and Anagyris foetida, were analyzed for their affinity for nicotinic and/or muscarinic acetylcholine receptors. Of the compounds tested, the alpha-pyridones, N-methylcytisine and cytisine, showed the highest affinities at the nicotinic receptor, while several quinolizidine alkaloid types were especially active at the muscarinic receptor. PMID- 7798969 TI - Yunnanxane and its homologous esters from cell cultures of Taxus chinensis var. mairei. AB - From cell cultures of Taxus chinensis var. mairei, yunnanxane [2 alpha, 5 alpha, 10-beta triacetoxy-14 beta-(2'-methyl-3'-hydroxyl)-butyryloxy-4(20),11-taxadiene, [1], and four new homologous esters, 2 alpha, 5 alpha, 10 beta, 14 beta- tetra acetoxy-4(20),11-taxadiene [2], 2 alpha, 5 alpha, 10 beta- triacetoxy-14 beta propionyloxy-4(20),11-taxadiene [3], 2 alpha, 5 alpha, 10 beta- triacetoxy-14 beta-isobutyryloxy-4(20),11- taxadiene [4], and 2 alpha, 5 alpha, 10 beta- triacetoxy-14 beta-(2'-methyl)-butyryloxy-4(20),11- taxadiene [5] have been isolated. Their structures were determined by spectroscopic methods. PMID- 7798971 TI - Management of neurological disorders: dementia. PMID- 7798970 TI - Growth factors: potential therapeutic applications in neurology. PMID- 7798972 TI - Cerebral amyloid angiopathy. PMID- 7798973 TI - White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates. AB - In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy control subjects, all without major cerbrovascular risk factors. The 133Xe inhalation method and the [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) technique with single photon emission computed tomography (SPECT) were used to measure rCBF. Rating scores for PVHs were significantly higher in the Alzheimer's disease group (p < 0.01) and correlated significantly with the volume of ventricles (p < 0.05) and with systolic arterial blood pressure (p < 0.01), but not with rCBF. By contrast, there was no significant difference in the rating scores or volumes of DWMHs between the two groups, although three patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p < 0.001), but not with frontal, temporal, parietal, or occipital rCBF. Postmortem histopathology of extensive DWMH lesions in one patient with definite Alzheimer's disease showed a partial loss of myelin and astrocytic gliosis, but no ischaemic changes. It is concluded that DWMH lesions may be associated with reduced rCBF in the hippocampal region. The heterogenous topography of neocortical rCBF deficits in Alzheimer's disease could not be explained by deafferentation from underlying white matter hyperintensities and therefore may reflect variations in the topography of cortical abnormalities. PMID- 7798974 TI - Dorothea Lynde Dix (1802-87). PMID- 7798976 TI - Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2 fluoro-2-deoxy-D-glucose and PET. AB - Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal. PMID- 7798977 TI - Radiological and neurophysiological changes in Japanese encephalitis. AB - Six patients with Japanese encephalitis, four males and two females whose age ranged between 2 and 47 years, were subjected to neurophysiological and radiological studies. An EEG in five of the patients showed diffuse delta wave activity and one had an alpha coma. Delta activity seems to be due to thalamic involvement, which was seen on CT of two and MRI of all the patients. The thalamic lesions were characteristically bilateral and were haemorragic in five. Changes on MRI included abnormalities of the brainstem in three and the basal ganglia and spinal cord in one patient each. Lower motor neuron signs were present in three patients but abnormal MRI signals in the spinal cord were present in only one out of three patients in whom spinal MRI was carried out. Central motor conduction time in the upper limb was prolonged in three patients (five sides) and in the lower limbs in one (both sides), which was consistent with involvement of the cerebral cortex, thalamus, brainstem, and spinal cord. Changes in MRI and EEG in the acute stage may provide early diagnostic clues in patients with Japanese encephalitis. PMID- 7798975 TI - Comparison of magnetic resonance angiography, duplex ultrasound, and digital subtraction angiography in assessment of extracranial internal carotid artery stenosis. AB - The results of a prospective study comparing ultrasound, intra-arterial digital subtraction angiography, and magnetic resonance angiography in the assessment of the degree of extracranial internal carotid artery stenosis are reported in patients with symptoms of recent carotid territory ischaemia. A total of 70 patients and 137 vessels were examined by all three techniques. The results obtained by each technique were reported blind. The mean difference (SD) for the comparison of magnetic resonance angiography and digital subtraction angiography was -0.7 (14)%, for ultrasound and digital subtraction angiography 3.1 (15)%, and for magnetic resonance angiography and ultrasound -3.8 (15)%. The level of agreement was greater for the more tightly stenosed vessels. With the assumption that the results of the digital subtraction angiogram reflect the true situation, the sensitivity and specificity in the detection of > or = 30% stenoses were 93% and 82% with ultrasound and 89% and 82% with magnetic resonance angiography; for stenoses > or = 70% 93% and 92% with ultrasound and 90% and 95% with magnetic resonance angiography; and for stenoses of 70-99% 89% and 93% with ultrasound and 86% and 93% with magnetic resonance angiography. For occlusion the values were 93% and 99% with ultrasound and 80% and 99% with magnetic resonance angiography. Increased sensitivity and specificity were obtained when analysis was confined to those vessels in which ultrasound and magnetic resonance angiography were in agreement over classification. It is thus possible to accurately categorize the degree of stenosis of the extracranial internal carotid artery from a combination of ultrasound and magnetic resonance angiography. The adoption of this combination for the investigation of patients before carotid endarterectomy removes the risk associated with conventional angiography and represents an important advance in the management of carotid stenosis. PMID- 7798978 TI - Presynaptic inhibition of soleus Ia afferent terminals in Parkinson's disease. AB - The possible role of changes in presynaptic inhibition of muscle spindle primary afferent terminals in Parkinson's disease was investigated. The pathway from tibialis anterior Ia afferents to soleus Ia terminals was assessed in 20 patients with Parkinson's disease and in 17 age matched controls, both at rest and during maintenance of tonic plantar flexing torques about the ankle. At all torques less presynaptic inhibition was present in the patients with Parkinson's disease than in the controls. The difference was significant at rest (p < 0.03) and at 2 Nm (p < 0.05) but not at 5 Nm and 7 Nm torque. The amount of presynaptic inhibition did not change with torque in either group. The observed alteration in presynaptic inhibition in Parkinson's disease is likely to make only a small contribution to the rigidity and impaired movement control. PMID- 7798980 TI - Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. AB - Clinical, radiological, and histopathological features of 51 surgically treated gangliogliomas were evaluated retrospectively. The most common presenting symptoms were epileptic seizures (47 patients (92%)). Focal neurological deficits occurred in 8% of the patients. The duration of symptoms at the time of operation ranged from three months to 45 years, mean 11 years. The temporal lobe was affected in 43 patients (84%), the frontal lobe in five patients (10%), and the occipital lobe in one patient (2%). Two of the tumours (4%) were localised infratentorially. On MRI, solid tumour parts usually showed a pronounced signal increase on proton density images and a less pronounced signal increase on T2 weighted images, whereas solid components were mainly isointense on T1 weighted images. Contrast enhancement was noted in 16 of 36 patients (44%). Cystic tumour parts were found in 23 of 40 patients (57%), all characterised by signal increase on T2 weighted images and decreased T1 signals. Signal deviation of cystic tumour parts on proton density images was variable. Computed tomography was performed in 17 patients and showed hypodense lesions in 10 (59%), and calcifications in seven (41%) cases. Surgery included complete tumour removal in 44 patients (86%) and partial resection in seven (14%). In six patients (12%) there were transient postoperative complications. One patient (2%) died postoperatively due to pulmonary embolism. Histopathological examination of the surgical specimens showed low grade gangliogliomas in 49 cases (96%) and anaplastic gangliogliomas in two (4%). Control MRI of 31 patients with a mean follow up period of 16 months was uneventful in all but one case of an anaplastic ganglioglioma. In all patients in whom the ganglioglioma was associated with medically intractable seizures the operation resulted in complete relief of seizures or a noticeable improvement of the epilepsy. PMID- 7798979 TI - Brain and muscle energy metabolism studied in vivo by 31P-magnetic resonance spectroscopy in NARP syndrome. AB - Phosphorus magnetic resonance spectroscopy (31P-MRS) was used to study in vivo the energy metabolism of brain and skeletal muscle in two members of an Italian pedigree with NARP syndrome due to a point mutation at bp 8993 of mtDNA. In the youngest patient, a 13 year old girl with retinitis pigmentosa, ataxia, and psychomotor retardation, there was an alteration of brain energy metabolism shown by a decreased phosphocreatine content, increased [ADP] and decreased phosphorylation potential. The energy metabolism of her skeletal muscle was also abnormal, as shown by resting higher inorganic phosphate and lower phosphocreatine concentrations than in normal subjects. Her mother, a 41 year old woman with minimal clinical involvement, showed a milder derangement of brain energy metabolism and normal skeletal muscle. Findings with MRS showed that this point mutation of mtDNA is responsible for a derangement of energy metabolism in skeletal muscle and even more so in the brain. PMID- 7798981 TI - Extrapyramidalism in Alzheimer's disease: prevalence, psychiatric, and neuropsychological correlates. AB - The prevalence and clinical correlates of extrapyramidal signs in a consecutive series of 78 patients with Alzheimer's disease attending a neurology clinic, and 20 age comparable normal controls, were examined. Based on the unified Parkinson's disease rating scale (UPDRS) findings, 18 patients (23%) met criteria for parkinsonism, 44 (56%) had isolated extrapyramidal signs, and 16 (21%) had no extrapyramidal signs. Whereas the control group showed a similar prevalence of isolated extrapyramidal signs (57%), none of them showed parkinsonism. No significant differences were found for age, sex, duration of illness, and severity of dementia among the three Alzheimer's disease groups. Patients with Alzheimer's disease-parkinsonism, however, showed a significantly higher frequency of major depression and dysthymia and significantly higher Hamilton depression scores than patients with isolated or no extrapyramidal signs. Patients with Alzheimer's disease-parkinsonism also showed significantly more deficits on frontal lobe related tasks such as the Wisconsin card sorting test, trail making test, and verbal fluency, as well as on tests of constructional praxis and abstract reasoning than patients with Alzheimer's disease but no extrapyramidal signs. In conclusion, the study showed a specific association between Alzheimer's disease and parkinsonism, as well as significant relations between parkinsonism, deficits in executive functions, and depression among patients with Alzheimer's disease. PMID- 7798982 TI - A neuropsychological instrument adding to the description of patients with suspected cortical dementia: the Milan overall dementia assessment. AB - A new, short, neuropsychologically oriented test for dementia assessment--the Milan Overall Dementia Assessment (MODA)--is described. Age and education adjusted norms based on 217 healthy controls are given. A validation study on 312 outpatients suspected of dementia (121 with probable Alzheimer's disease) showed that the MODA differentiated patients with cognitive impairment from normal subjects more effectively than did the DSM III-R. The correlation between the MODA and the mini mental state examination was 0.63 in controls and 0.84 in patients with Alzheimer's dementia. The MODA test-retest reliability was 0.83. The test proved to be well suited to longitudinal studies. PMID- 7798983 TI - Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. AB - A group of patients with damage to the ventral part of the frontal lobes was severely impaired relative to a group of patients without damage in this area (the non-ventral group) in the reversal and in the extinction of simple visual discrimination tests. In these tests they continued to make responses to a previously rewarded stimulus. Patients often reported verbally that the contingencies had changed, but were unable to alter their behaviour appropriately. These impairments occurred independently of IQ or verbal memory impairments. The perseverative touching of a previously rewarded stimulus is consistent with work with non-human primates showing impaired reversal and extinction after orbitofrontal lesions. Performance on these reversal and extinction tests was highly correlated with scores obtained on a behaviour questionnaire, which reflected the degree of disinhibited and socially inappropriate behaviour exhibited by patients. It is suggested that a difficulty in modifying responses, especially when followed by negative consequences, as manifested in these simple laboratory tests, may contribute to the inappropriate behaviour shown in daily life by patients with frontal lobe damage. PMID- 7798984 TI - Chronic idiopathic axonal polyneuropathy: a five year follow up. AB - Seventy five patients with chronic idiopathic axonal polyneuropathy (CIAP) were studied for five years. The standardised and quantified neurological examination shows that progression of CIAP is slow, and handicap, if present, is not severe. During the follow up period a definite cause of the neuropathy was found in only four patients (two hereditary motor and sensory neuropathy type 2, one sensory chronic inflammatory demyelinating polyneuropathy, one alcoholic neuropathy). At the end of the follow up CIAP was not related to malignancy or gammopathy. Routine repetition of laboratory tests was not informative and these tests should be performed on clinical grounds only. PMID- 7798985 TI - Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy. AB - Slit-hyperintensity in the outer margin of the putamen on T2 weighted MRI was found in 17 out of 28 patients with clinically diagnosed multiple system atrophy. Thirteen of these 17 patients showed extrapyramidal signs. Five patients had only unilateral slit-hyperintensity; four of them had contralateral rigidity; and one had bradykinesia. Despite mild rigidity, one case showed no slit-hyperintensity. One of the 14 cases with parkinsonism showed no hyperintensity, and four of the 14 cases without parkinsonism showed hyperintensity. On the other hand, slit hyperintensity was not seen in any of 25 patients with clinically diagnosed Parkinson's disease. Putaminal slit-hyperintensity is a useful MRI feature in the differential diagnosis between Parkinson's disease and multiple system atrophy predominantly affecting the extrapyramidal system. PMID- 7798986 TI - Ability to modulate walking cadence remains intact in Parkinson's disease. AB - Gait hypokinesia (slowness) is a characteristic feature of Parkinson's disease. It is not clear, however, whether the slowness is due to a problem in regulation of the timing of consecutive steps or the control of stride size. Examination of cadence control for slow to medium walking speeds has shown an increase in step frequency that was a compensation for reduced stride length. In this investigation the ability of Parkinsonian patients to modulate their cadence (steps per minute) at the fast walking speeds exhibited by age and height matched controls was examined. The findings indicated that cadence control remains unaffected throughout its entire range in Parkinson's disease and that gait hypokinesia is directly attributable to an inability to internally generate sufficiently large steps. PMID- 7798987 TI - Optimisation of botulinum treatment for cervical and axial dystonias: experience with a Japanese type A toxin. AB - Twenty two patients with cervical and axial dystonias were treated with Japanese type A botulinum toxin. Injections were given repeatedly at intervals of 28-30 days to carefully chosen muscles with increased activities, with a maximum dose per session of 300 units. The maximum improvements in subjective and objective ratings were obtained only after repeated injections. No anti-toxin antibodies were detected; nor did any muscle fail to respond to the toxin. During the treatment, previously "silent" muscles were activated to reproduce the original abnormal posture, as if driven by a central motor programme. This resistance to treatment was overcome by injecting the toxin into newly activated muscles. Repeated injections are thus required to override central mechanisms in dystonias or to maximise drug delivery to large muscles. Antibody development may be controlled by the use of a less immunogenic toxin. PMID- 7798988 TI - Click-evoked vestibular activation in the Tullio phenomenon. AB - Click-evoked vestibulocollic reflexes were studied in a patient with a unilateral Tullio phenomenon (sound induced vestibular symptoms) and the findings were compared with those of a group of normal subjects. Compared with normal subjects, the reflexes elicited from her symptomatic side were large and had an abnormally low threshold, but retained a normal waveform. The click-evoked responses in this patient show changes consistent with her symptomatology and are indicative of a pathological increase in the normal vestibular sensitivity to sound. PMID- 7798990 TI - Vertebrobasilar dolichoectasia and exertional headache. PMID- 7798989 TI - A patient with one limb interstitial myositis with localised lipoatrophy presenting with severe cramps and fasciculations. AB - A case of interstitial myositis associated with a localised lipoatrophy is reported. The patient is a 24 year old man who presented with severe painful cramps and fasciculations localised to one limb. The rarity of both disorders, and their likely common autoimmune mechanism, suggest that this is not a chance association. PMID- 7798991 TI - Cholinergic supersensitivity of the iris in Alzheimer's disease. PMID- 7798992 TI - Rheumatic chorea and lupus anticoagulant. PMID- 7798993 TI - Acute peripheral neuropathy, rhabdomyolysis, and severe lactic acidosis associated with 3243 A to G mitochondrial DNA mutation. PMID- 7798994 TI - Papilloedema and visual failure in a patient with nocturnal hypoventilation. PMID- 7798995 TI - Hemichorea reversible after operation in a boy with cavernous angioma in the head of the caudate nucleus. PMID- 7798996 TI - The nature of apraxia in corticobasal degeneration. PMID- 7798997 TI - Transient epileptic amnesia--a clinical update and a reformulation. PMID- 7798998 TI - Hypokinesia of associated movement in Parkinson's disease: a symptom in early stages of the disease. AB - We compared the degrees of impairment between intended voluntary movement and its simultaneous automatic associated movement in Parkinson's disease (PD). We studied wrist dorsiflexion as a movement associated with grip in 20 patients with PD and in 20 normal controls. The patients showed a significantly smaller dorsiflexion as compared with the controls. The decrease in associated movement was related to the severity of clinical stage of the disease, while gripping was performed well in each stage. The temporal relationship between grip and associated movement was the same for both groups of subjects. The patients showed no disturbance of amplitude or velocity for a single motor act of wrist dorsiflexion. Persons with PD have a greater reduction of automatic associated movement than intended voluntary movement. This may be one of the bases of clinical symptoms of PD patients in early stages of the disease. PMID- 7798999 TI - Astereopsis induced by repetitive magnetic stimulation of occipital cortex. AB - Three healthy subjects underwent repetitive transcranial magnetic stimulation (20 Hz, 1 s) with a round oil-cooled coil held tangentially against the skull surface 3 or 4 cm above the inion, while viewing a random-dot stereogram through red green glasses. The coil was positioned over the midline of the bilateral superior occipital lobes. All three subjects experienced loss of stereoscopic perception during stimulation. A stimulus duration of more than 0.2 s and a stimulus frequency of more than 10 Hz seem to be necessary to disrupt the cortical mechanisms involved in global stereopsis. Repetitive magnetic stimulation easily and painlessly produced a reversible disturbance in global stereopsis. The results suggest that the bilateral superior occipital cortices are involved in the perception of global stereopsis. PMID- 7799001 TI - The Dementia Rating Scale in Alzheimer's disease, Huntington's disease and progressive supranuclear palsy. AB - The Dementia Rating Scale (DRS) comprises a series of five subtests which assess attention, memory, initiation/preservation, construction, and conceptualisation. It can be delivered in full in approximately 30 min, making it a useful test for the detection and estimation of the overall level of dementia. We analysed the pattern of subscale test scores in patients with cortical and subcortical dementias, who were matched for their overall level of dementia on this scale. Patients with dementia of Alzheimer's type were more impaired than patients with Huntington's disease (HD) and progressive supranuclear palsy (PSP) on the memory subtest, whereas patients with HD and PSP were more impaired on the initiation/perseveration subtest. This is evidence in favour of the concept of cortical and subcortical dementias as separate, although overlapping, entities. Qualitative differences in the pattern of cognitive impairment in these disorders can be detected with a brief cognitive status examination. PMID- 7799000 TI - Differentiation of herpes simplex virus 1 and 2 in cerebrospinal fluid of patients with HSV encephalitis and meningitis by stringent hybridization of PCR amplified DNAs. AB - Differentiation of herpes simplex virus (HSV) types 1 and 2 in cerebrospinal fluid of 17 patients with serologically diagnosed HSV encephalitis and meningitis or acute limbic encephalitis was determined by stringent hybridization of polymerase chain reaction--amplified DNAs. Ten of 17 patients were positive; six with HSV 1 isolates and four with HSV 2 isolates. We detected HSV type 1 in two cases of meningitis, although meningitis is generally thought to be caused by type 2. Additionally, HSV type 2 was found in one case of acute adult encephalitis, which is generally due to HSV type 1. HSV DNAs could be detected for over 1 month after onset, although our patients included several prolonged and recurrent cases. HSV DNA genomes were not detected in three cases of acute limbic encephalitis. Our study indicates that this method can be used for type differentiation in HSV CNS infections. PMID- 7799002 TI - The "jerky dystonic unsteady hand": a delayed motor syndrome in posterior thalamic infarctions. AB - We report the cases of three patients with a thalamic infarct in the territory of the posterior choroidal artery involving the posterior thalamic nuclei. These patients developed delayed complex hyperkinetic motor syndromes, associating ataxia, tremor, dystonia, myoclonus and chorea, which we call "the jerky dystonic unsteady hand". One patient had a severe myoclonic and ataxic-dystonic choreoathetosis; another showed a so-called rubral tremor (myoclonic ataxia with resting, action, and wing-beating tremor) with dystonia; and the third one had a dystonic and ataxic hand with intermittent mild action myoclonus. All of them had sensory dysfunction; two had also presented with a painful Dejerine-Roussy syndrome. All had CT or MRI-proven infarcts in the territory of the posterior cerebral artery involving the posterior choroidal territory with an abnormal signal in the posterior area of the thalamus (pulvinar nucleus) but sparing the other thalamic, subthalamic and midbrain structures. These delayed myoclonic complex hyperkinetic syndromes have not been reported before, and we did not observe them in other topographic forms of thalamic infarcts. They may thus represent a new entity of movement disorders due to lesions in the posterior thalamic nuclei, with specificity for posterior choroidal artery infarcts. PMID- 7799003 TI - Usefulness of movement time in the assessment of Parkinson's disease. AB - Reaction time (RT) and movement time (MT) are reported to be delayed in Parkinson's disease (PD), but their clinical utility and relationship with clinical findings is still uncertain. We investigated RT and MT in 22 PD patients at baseline conditions and following acute oral trials of levodopa and biperiden, an anticholinergic drug. At baseline conditions, RT and MT of PD patients were abnormally delayed compared with those of 16 normal control subjects. Both RT and MT were longer in more severely affected patients compared with the mild PD patients; in the mild PD patients with asymmetrical signs both responses were longer on the more affected side. Bradykinesia was the clinical symptom that best correlated with the objective measurements, with a stronger correlation for MT than for RT. The oral administration of levodopa significantly improved both the responses, whereas biperiden was ineffective. The magnitude of RT and MT improvement after levodopa differed; MT improvement was related to PD severity, whereas RT improvement was not. These results suggest that MT, rather than RT, is an objective, simple, and reliable tool to evaluate bradykinesia and its levodopa induced modifications in PD. PMID- 7799005 TI - Central alveolar hypoventilation associated with paraneoplastic brain-stem encephalitis and anti-Hu antibodies. AB - We describe a patient with a paraneoplastic brain-stem encephalitis due to an occult small cell carcinoma of the lung. He developed episodes of central sleep apnoea culminating in acute respiratory failure. Antibodies resembling anti-Hu antibodies were demonstrated in both serum and cerebrospinal fluid. PMID- 7799004 TI - Laryngeal electromyography with separated surface electrodes in patients with multiple system atrophy presenting with vocal cord paralysis. AB - When recording the activity of the posterior cricoarytenoid muscle (PCA) with surface electrodes, there is contamination from the surrounding muscles such as the cricopharyngeal muscle. We therefore devised a new oesophageal catheter electrode of the separate type, having three individual surface electrodes for the PCA, cricopharyngeal muscle and diaphragm. The records obtained with this catheter demonstrated satisfactory separation between PCA and cricopharyngeal muscle activities. We used this catheter in patients with multiple system atrophy presenting with vocal cord paralysis, who were awake or asleep. There were two interesting electromyographical findings, which were inspiratory activity of the adductor muscle (the thyroarytenoid muscle) and fade-out of the abductor muscle, that is, PCA activity during sleep. Although vocal cord paralysis is one of the most serious life-threatening complications, the precise mechanism has not been clarified. We believe that our catheter may be useful in investigating the mechanism of vocal cord paralysis which could cause sudden death in neurodegenerative disorders, including multiple system atrophy. PMID- 7799007 TI - The "anterior operculum syndrome". PMID- 7799006 TI - Valproate encephalopathy and hypocarnitinaemia in diabetic patients. AB - Two patients with epilepsy and diabetes mellitus developed encephalopathy while on valproate monotherapy. Low plasma carnitine levels were found. Discontinuation of valproate was followed by clinical recovery and normalization of carnitine levels. Both valproate treatment and diabetes mellitus may contribute to secondary carnitine deficiency, with resultant encephalopathy. Thus, diabetic patients may be at increased risk of developing valproate encephalopathy associated with hypocarnitinaemia. PMID- 7799008 TI - Chemotherapy in acute myelogenous leukemia: high dose, higher expectations? PMID- 7799009 TI - Risk of second aerodigestive cancers increases in patients who survive free of small-cell lung cancer for more than 2 years. AB - PURPOSE: Patients who survived small-cell lung cancer (SCLC) for more than 2 years were evaluated to determine the frequency and anatomic pattern of redevelopment of small-cell cancer and development of non-small-cell lung cancer (NSCLC) and aerodigestive cancers with the passage of time. PATIENTS AND METHODS: From April 1973 through December 1991, 578 patients with previously untreated SCLC were entered onto prospective therapeutic trials at the National Cancer Institute (NCI), Bethesda, MD. Sixty-two (11%) were cancer-free 2 years after initiation of therapy and were assessable for redevelopment of SCLC and development of NSCLC, and aerodigestive cancers. RESULTS: Twenty patients redeveloped SCLC 2.0 to 12.2 years after initiation of chemotherapy, of whom two patients were deemed to have a second primary small-cell cancer that involved the aerodigestive tract. Fifteen patients developed 16 cancers in the lung other than SCLC 3.4 to 14.9 years after initiation of therapy. Two developed other aerodigestive cancers that involved the larynx and lip. The risk of a NSCLC and aerodigestive cancer in these patients increased more than sixfold from 2% per patient per year during years 2 to 4 to 12.6% and 14.4%, respectively, after more than 10 years. The cumulative actuarial risk of a second primary NSCLC or aerodigestive cancer at 16 years is 69% and 72%, respectively. CONCLUSION: The increasing risk of second aerodigestive cancers with the passage of time is a mounting problem for patients cured of SCLC. Chemoprevention trials for these patients should be considered. PMID- 7799010 TI - Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial. AB - PURPOSE: To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML). PATIENTS AND METHODS: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months. RESULTS: Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival. CONCLUSION: These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only. PMID- 7799011 TI - Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. AB - PURPOSE: In a previous randomized trial, the addition of adjuvant chemotherapy to postoperative radiotherapy proved beneficial in the treatment of childhood high grade astrocytomas. The present study tests the hypothesis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study. PATIENTS AND METHODS: Between April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly diagnosed high-grade astrocytomas were eligible for this study, as determined by the treating institution's histopathologic diagnosis. Treatment consisted of postoperative local-field radiotherapy and adjuvant chemotherapy, either lomustine (CCNU), vincristine, and prednisone (control regimen) or eight drugs-in-1-day chemotherapy (experimental regimen). Two cycles of postoperative preirradiation chemotherapy were administered in the experimental regimen. Patients were evaluated radiographically every 3 months after irradiation. RESULTS: Eighty-five eligible patients were randomized to the control regimen and 87 to the experimental regimen. The progression-free survival (PFS) and overall survival (OS) at 5 years were 33% (SE = 5%) and 36% (SE = 6%), respectively. There was no statistical difference in outcome between the two chemotherapy regimens. In patients with confirmed diagnoses of anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM), anaplastic astrocytoma, greater than 90% resection, and nonmidline tumor location were characteristics predictive of an improved PFS. There was a difference in toxicity between the two chemotherapeutic regimens, with greater myelosuppression and hearing loss in the experimental regimen. Tumor recurrence occurred primarily within the primary tumor site. CONCLUSIONS: There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone. Extent of tumor resection and histopathologic diagnosis are significant prognostic variables. The overall outcome for children with high grade astrocytomas remains poor. PMID- 7799012 TI - Results of the United Kingdom Children's Cancer Study Group first Wilms' Tumor Study. AB - PURPOSE: The first United Kingdom Children's Cancer Study Group (UKCCSG) Wilms' Tumor Trial (UKW1) applied treatment regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria, seeking to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable histology (UH) tumors with more intensive chemotherapy. PATIENTS AND METHODS: Three hundred eighty-four consecutively diagnosed patients with Wilms' tumor were recruited from the 20 UKCCSG centers and Oslo, Norway, between January 1980 and June 1986. The regimen for stage I patients was vincristine (Vcr) only, while stage II patients received Vcr and dactinomycin (Act-D). Stage III patients received three-drug therapy and stage IV and UH patients four-drug regimens. Act D was given as pulsed doses of 1.5 mg/m2 every 3 or every 6 weeks. No lung irradiation was used in stage IV patients. No randomized comparisons were attempted. End points were survival and event-free survival (EFS). RESULTS: Survival at 6 years in FH patients was 96% for stage I, 93% for stage II, 83% for stage III, 65% for stage IV, and 50% for UH patients of all stages. CONCLUSION: Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias. PMID- 7799014 TI - Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. AB - PURPOSE: To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS: Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS: The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty. PMID- 7799013 TI - Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen. AB - PURPOSE AND METHODS: Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy. RESULTS: Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure. CONCLUSION: There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes. PMID- 7799015 TI - Ketoconazole in the management of paraneoplastic Cushing's syndrome secondary to ectopic adrenocorticotropin production. AB - PURPOSE: To evaluate the safety and efficacy of ketoconazole treatment in the management of patients with paraneoplastic Cushing's syndrome (CS) secondary to ectopic adrenocorticotropin (ACTH) production by malignant neoplasms (ECS). PATIENTS AND METHODS: A retrospective chart review was undertaken for 15 consecutive patients with ECS treated with ketoconazole. Strict criteria were defined for diagnosis of ECS and for clinical, biochemical, and hormonal responses. RESULTS: There were four women and 11 men with a median age of 59 years (range, 44 to 84). Eleven patients had primary lung cancer (nine small-cell [SCLC], one mixed SCLC/non-SCLC, and one non-SCLC); two had carcinoid tumors (one bronchial, one pancreatic); one had hepatocellular carcinoma; and one had medullary carcinoma of the thyroid. Eight patients had ECS diagnosed at tumor presentation. Clinical findings included proximal muscle weakness (n = 10), peripheral edema (n = 8), and hypertension (n = 8). Biochemical abnormalities included hypokalemia (n = 14), metabolic alkalosis (n = 13), and new or worsened diabetes mellitus (n = 10). Patients received ketoconazole in dosages of 400 to 1,200 mg/d titrated by changes in urinary free-cortisol (UFC) levels for a median duration of 26 days (range, 3 to 1,059), and nine also received chemotherapy with ketoconazole. Hypokalemia, metabolic alkalosis, diabetes mellitus, and hypertension improved in the majority of patients. Ten patients had a hormonal response, with seven complete responses (median duration, 25 days; range, 6 to 989). The occurrence of symptomatic hypoadrenalism was definite in three patients and probable in one. Most patients died of progressive malignant disease accompanied by escape from hormonal control by ketoconazole. The median survival duration of the group was 19 weeks (range, 1 to 154). CONCLUSION: Ketoconazole results in biochemical and hormonal improvement for most patients with ECS. It has few adverse effects, but may impair the cortisol response to stress. For that reason, replacement corticosteroids should be considered for patients with hormonal response, and moderate- to high-dose corticosteroids should be given for any potential stress situations. The ultimate control of the syndrome is dependent on successful treatment of the underlying tumor. PMID- 7799016 TI - Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. AB - PURPOSE: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. PATIENTS AND METHODS: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. RESULTS: Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. CONCLUSION: Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity. PMID- 7799017 TI - Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration. AB - PURPOSE: Intralumbar methotrexate is one of the primary therapeutic modalities for the prevention and treatment of meningeal leukemia. However, methotrexate distribution to the ventricles is limited and highly variable following intralumbar dosing, and cytotoxic concentrations of methotrexate are not always achieved or sustained in the ventricular CSF. We used a nonhuman primate model to determine the effect of body position on the caudal distribution of an intralumbar dose of methotrexate. METHODS: Methotrexate (1.0 mg) was administered by intralumbar injection to four animals, which were then immediately placed either in an upright sitting position or in a prone position for 1 hour, then upright. Each animal served as its own control and was studied in each position on at least one occasion. RESULTS: The mean peak ventricular methotrexate concentration was 0.12 mumol/L (range, 0.091 to 0.20) in animals that were immediately placed upright, compared with 2.81 mumol/L (range, 0.21 to 8.9) in animals that remained prone for 1 hour. The mean area under the concentration versus-time curves (AUC) was 0.51 mumol/L.h (range, 0.26 to 1.1) in the upright animals and 12.0 mumol/L.h (range, 0.9 to 35.4) in the prone animals. CONCLUSION: Maintaining a prone position for 1 hour after an intralumbar dose increased the peak methotrexate concentration and drug exposure in ventricular CSF. CSF drug distribution following intralumbar therapy can be influenced by body position after the injection. PMID- 7799018 TI - Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. AB - PURPOSE: To characterize and model the disposition of paclitaxel in humans and define a pharmacodynamic relationships between paclitaxel disposition and its toxicity and efficacy. PATIENTS AND METHODS: Paclitaxel pharmacokinetics were studied in 55 courses of therapy in 30 patients. Paclitaxel was administered at 135 mg/m2 or 175 mg/m2 by either a 3- or a 24-hour infusion schedule to patients with advanced ovarian cancer (n = 15), or at 225 mg/m2 by 3-hour infusion to patients with advanced breast cancer (n = 15). Paclitaxel and 6 alpha hydroxylpaclitaxel were quantified by high-performance liquid chromatography (HPLC). Pharmacokinetics were assessed by noncompartmental and model-dependent methods. Pharmacodynamic correlations were evaluated statistically and by regression models. RESULTS: Paclitaxel disposition is nonlinear in humans and, on the 3-hour schedule, 6 alpha-hydroxylpaclitaxel was identified in the plasma of all patients treated. The plasma disposition of paclitaxel and 6 alpha hydroxylpaclitaxel was well described by a model that featured multiple nonlinear processes. Neutropenia was not related to the areas under the curves (AUCs) of paclitaxel or 6 alpha-hydroxylpaclitaxel, or to palitaxel peak concentrations (Cmax). Neutropenia was related to the duration that plasma concentrations were > or = 0.05 mumol/L, a relationship that is well described by a sigmoid maximum response (Emax) model. CONCLUSION: The disposition of paclitaxel in humans is nonlinear. Paclitaxel metabolism to 6 alpha-hydroxylpaclitaxel is likely an important detoxification pathway. Myelosuppression is related to the duration that plasma paclitaxel concentrations are > or = 0.05 mumol/L. Trials of new doses and schedules of paclitaxel should take into account its nonlinear disposition to rule out adverse clinical consequences, especially if the drug is administered by short infusion. Our pharmacokinetic model should prove to be a powerful tool in predicting paclitaxel disposition, regardless of dose and schedule, and should facilitate further pharmacodynamic investigations. PMID- 7799019 TI - Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. AB - PURPOSE: Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a randomized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy. PATIENTS AND METHODS: The effect of four factors associated with lymphadenectomy on microscopic tumor-node metastasis (TNM) staging, and on stage-specific survival rates was assessed in 473 curatively resected patients. RESULTS: After application of extended lymphadenectomy, additional information on N status was available, only in R2 resections with up-staging to N2 status in 30% of patients. The calculated effect of this stage migration on known 5-year survival rates was as follows: an increase of 1% in TNM stage Ia, 2% in Ib, 7% in II, 15% in IIIa, and 15% in IIIb. A further increase in survival was observed by stage migration to N3 or N4 status, due to selective extension of lymphadenectomy to clinically overt metastases located outside the allocated level of clearance (contamination). Incomplete lymphadenectomy of N1- or N2-level stations indicated for dissection (noncompliance) demonstrates that more migration can occur when strictly adhering to the protocol. Examining more nodes per N level (diligence) induces even more migration, since the number of nodes that were histologically examined per N level correlated significantly with nodal status (lymph node-negative [N-] or lymph node-positive [N+]). CONCLUSION: These factors explain, at least partially, superior stage-specific survival rates after R2 compared with R1 resections, without a real survival benefit in individual patients. PMID- 7799020 TI - Clinical and pharmacologic analysis of hyperfractionated daily oral etoposide. AB - PURPOSE: The antitumor effect of etoposide is increased by maintaining a low blood level, whereas high peak levels may cause myelotoxicity. We investigated whether a constant low blood level could be obtained by the administration of oral etoposide three times daily. PATIENTS AND METHODS: Nineteen patients with non-small-cell lung cancer were treated with oral etoposide (25 mg three times daily for 21 days) as monotherapy or in combination with cisplatin 80 mg/m2. A pharmacokinetic model that predicted the mean blood concentration (Cmean) was developed in the 10 patients on etoposide monotherapy and validated in the nine patients on combination chemotherapy. Pharmacodynamic relationships were evaluated in each group. RESULTS: Etoposide dose per body-surface area ranged from 45 to 63 mg/m2/d (median, 53), but did not correlate with plasma level. Cmean was 1.1 +/- 0.3 micrograms/mL. Peak concentrations ranged from 0.6 to 2.5 micrograms/mL. The intrapatient coefficient of variation for plasma etoposide concentrations was 22% +/- 10%. Cmean was accurately estimated as follows: Cmean = 0.098 + 0.413 x C0 + 0.458 x C2 (r = .97, P = .0001), where C0 and C2 represent concentrations before and 2 hours after administration. This model was unbiased (mean predictive error [MPE], 0.0 microgram/mL) and precise (root mean square error [RMSE], 0.1 microgram/mL). Leukopenia was the major toxicity. The surviving fraction of leukocytes (SF; nadir count/pretreatment count) was correlated to Cmean as follows: SF = 0.87 - 0.34 x Cmean (r = .67, P = .03) in the monotherapy group and SF = 0.64 - 0.33 x Cmean (R = .77, P = .03) in the combination chemotherapy group. Two and four patients treated with monotherapy and combination chemotherapy showed responses, respectively. All responders had a Cmean > or = 1.0 microgram/mL. CONCLUSION: Hyperfractionated oral etoposide achieveda stable plasma level that could be predicted by measurement at only two times. PMID- 7799021 TI - Phase I clinical and pharmacokinetic study of oral etoposide phosphate. AB - PURPOSE: To determine the bioavailability (F) and the pharmacokinetic profile of both etoposide and its prodrug, etoposide phosphate, after oral and intravenous administration of etoposide phosphate, and to determine the maximum-tolerable dose (MTD) of oral etoposide phosphate administered daily for 5 consecutive days every 3 weeks. In addition, we sought to develop and validate two limited sampling models (LSMs) to predict the etoposide area under the curve (AUC) 24 hours after administration of oral and intravenous etoposide phosphate. PATIENTS AND METHODS: In the F part of the study, patients were assessed for pharmacokinetic studies after one oral and one intravenous administration of the same dose of etoposide phosphate. Etoposide phosphate and etoposide plasma concentrations were assayed by high-performance liquid chromatography (HPLC). To develop LSMs after oral and intravenous administration, patients were randomized between the training and validation data sets. In the phase I part of the study, which followed the F part, the dose of etoposide phosphate was escalated from 50 mg/m2/d for etoposide equivalents for 5 days to 220 mg/m2/d for 5 days. RESULTS: Forty adult patients with solid tumors or lymphoma entered the study and 35 were assessable for toxicity. The MTDs were defined as 175 mg/m2 and 220 mg/m2 in previously treated and untreated patients, respectively. Neutropenia was dose limiting, with high interpatient variability. Within 15 minutes after intravenous administration, etoposide phosphate was no longer detectable in plasma, and it was never detectable after oral administration. Plasma concentrations and pharmacokinetic parameters of etoposide following etoposide phosphate were comparable to those reported for etoposide. The relative F (mean +/- SD) of etoposide after oral etoposide phosphate was 76 +/- 27%, with a range of 37% to 144%. CONCLUSION: The clinical and pharmacokinetic results of this study confirm the prodrug hypothesis of etoposide phosphate. Although firm conclusions cannot be drawn, the F of oral etoposide phosphate seems to be comparable to or only slightly better than that of oral etoposide. PMID- 7799023 TI - Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea. AB - PURPOSE: Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with gastrointestinal malignancies and can result in severe morbidities or mortality. The somatostatin analog octreotide acetate has been used in the treatment of 5FU-induced diarrhea with promising results. A phase I trial was initiated to determine the maximum-tolerated dose of octreotide acetate that could be administered in this setting. PATIENTS AND METHODS: Patients were required to have National Cancer Institute Common Toxicity Criteria > or = grade 2 diarrhea or watery diarrhea secondary to treatment with 5FU or a modulated 5FU regimen. At least three patients were treated at each dose level; after satisfactory completion of this dose level (zero of three or one of six patients with < or = grade 2 toxicity), additional patients were added at the next dose level. Doses of octreotide acetate studied were 50 to 2,500 micrograms subcutaneously three times daily for 5 days. RESULTS: A total of 35 patients received 49 courses of therapy. The only significant toxicities occurred at 2,500 micrograms. At this dose level, one patient developed an allergic reaction with flushing, nausea, and dizziness after each of the first two injections. A second patient developed asymptomatic hypoglycemia with a serum glucose level of 26 mg/dL. The maximum-tolerated dose was 2,000 micrograms. The efficacy of the treatment correlated significantly (P = .01) with the dose of octreotide administered, and more patients completed the course of therapy at the higher doses. CONCLUSION: Octreotide acetate can be safely administered for the treatment of fluoropyrimidine-induced diarrhea in patients with gastrointestinal malignancies. The dose-limiting toxicities were allergic (nausea, rash, and light headedness) and endocrine (hypoglycemia). There was a significant correlation between complete response to therapy and octreotide dose. PMID- 7799022 TI - Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. AB - PURPOSE: A phase I study was undertaken to determine the maximum-tolerated dose (MTD), principal toxicities, and pharmacokinetics of the novel topoisomerase I inhibitor irinotecan (CPT-11). PATIENTS AND METHODS: Sixty-four patients meeting standard phase I eligibility criteria were included (24 women, 40 men; median age, 51 years; primary sites: colon, head and neck, lung, pleura; 60 of 64 had been previously treated). Pharmacokinetics was determined by high-performance liquid chromatography (HPLC). RESULTS: One hundred ninety CPT-11 courses were administered as a 30-minute intravenous (IV) infusion every 3 weeks (100 to 750 mg/m2). Grade 3 to 4 nonhematologic toxicities included diarrhea (16%; three hospitalizations), nausea and vomiting (9%), asthenia (14%), alopecia (53%), elevation of hepatic transaminases (8%), and one case of skin toxicity. An acute cholinergic syndrome was observed during CPT-11 administration. Diarrhea appeared dose-limiting at 350 mg/m2, but this was circumvented by using a high-dose loperamide protocol that allowed dose escalation. Dose-dependent, reversible, noncumulative granulocytopenia was the dose-limiting toxicity (nadir, days 6 to 9; median recovery time, 5 days). Grade 3 to 4 anemia was observed in 9% of patients. One patient died during the study, 8 days after CPT-11 treatment. Two complete responses (cervix, 450 mg/m2; head and neck, 750 mg/m2) and six partial responses in fluorouracil (5-FU)-refractory colon cancer were observed (260 to 600 mg/m2). Pharmacokinetics of CPT-11 and active metabolite SN-38 were performed in 60 patients (94 courses). CPT-11 plasma disposition was bi- or triphasic, with a mean terminal half-life of 14.2 +/- 0.9 hours (mean +/- SEM). The mean volume of distribution (Vdss) was 157 +/- 8 L/m2, and total-body clearance was 15 +/- 1 L/m2/h. The CPT-11 area under the plasma concentration versus time curves (AUC) and SN-38 AUC increased linearly with dose. SN-38 plasma decay had an apparent half-life of 13.8 +/- 1.4 hours. Both CPT-11 and SN-38 AUCs correlated with nadir leukopenia and granulocytopenia, with grade 2 diarrhea, and with nausea and vomiting. CONCLUSION: The MTD of CPT-11 administered as a 30-minute IV infusion every 3 weeks is 600 mg/m2, with granulocytopenia being dose-limiting. At 350 mg/m2, diarrhea appeared dose-limiting, but high-dose loperamide reduced this toxicity and allowed dose escalation. For safety reasons, the recommended dose is presently 350 mg/m2 every 3 weeks; more experience must be gained to establish the feasibility of a higher dose in large multicentric phase II studies. However, when careful monitoring of gastrointestinal toxicities is possible, a higher dose of 500 mg/m2 could be recommended in good-risk patients. The activity of this agent in 5-FU-refractory colorectal carcinoma makes it unique and mandates expedited phase II testing. PMID- 7799024 TI - Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. AB - PURPOSE: The purpose of this study was to determine the maximum-tolerated dose (MTD) of fluorouracil (5-FU) administered as a protracted intravenous (IV) infusion with concurrent radiation in patients with pancreaticobiliary carcinoma. METHODS: Twenty-five patients with recurrent, residual, or unresectable carcinoma of the pancreas or biliary tract were treated on a phase I trial of protracted IV infusions of 5-FU, beginning at 200 mg/m2/d, concurrent with radiation therapy (59.4 Gy in 33 fractions over 6 to 7 weeks). Chemotherapy began on the first day of radiation and continued through the entire course of treatment. After each cohort of five patients had been treated and observed, the daily dose was escalated in 25-mg/m2 increments until dose-limiting toxicity was encountered. An additional cohort of five patients was treated at the MTD. Clinical examination and computed tomography (CT) were used to evaluate response and patterns of progression. RESULTS: The MTD of 5-FU was 250 mg/m2/d. The dose-limiting toxicity was oral mucositis. The median survival duration of all patients treated was 11.9 months and the 2-year survival rate was 19%. Eleven of 25 patients remain free of local progression and four patients are without evidence of progression at 18+, 18+, 34+, and 44+ months following treatment. CONCLUSION: Concurrent radiation with protracted 5-FU infusion at 250 mg/m2/d is well tolerated and shows evidence of activity against tumors of the pancreas and biliary system. PMID- 7799025 TI - Complications of indwelling venous access devices in cancer patients. AB - PURPOSE: We undertook this study to review our experience with indwelling vascular access devices in cancer patients to identify factors associated with complications. PATIENTS AND METHODS: A total of 322 indwelling devices were placed in 274 cancer patients by a single surgeon. Devices were placed via percutaneous insertion in 72% (231 of 322) and via venous cutdown in 28% (91 of 322). We placed external catheters in 209 of 322 patients (65%) and subcutaneous infusion ports in 113 of 322 (35%). RESULTS: Pneumothorax occurred in four of 231 (1.7%) of the percutaneously placed devices. Postoperative complications included sepsis and thrombosis, which necessitated premature removal of the devices. Device related sepsis occurred in 28 of 209 patients (13%) with catheters and six of 113 patients (5%) with subcutaneous ports. Thrombosis occurred in 21 of 209 patients (10%) with catheters and seven of 113 (6%) with subcutaneous ports. In 15 of 19 devices removed for thrombosis, the tip was above the T3 level. Seventeen devices were placed in the saphenous vein, with a complication rate similar to that observed in upper-body devices. CONCLUSION: We found a significantly (P < .05, chi 2 analysis) increased incidence of thrombotic complications in patients with triple-lumen catheters (10 of 48) compared with double-lumen catheters (11 of 160), as well as a significantly (P < .05) decreased mean time until catheter failure (40 v 146 days). We also observed a significant increase in the rate of thrombosis in patients with a catheter tip above the T3 level. We therefore recommend the use of fluoroscopy at the time of placement to assure adequate catheter length and tip position and the use of triple-lumen catheters only when necessary for concurrent drug administration. PMID- 7799027 TI - Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma. AB - PURPOSE: To assess the prognostic significance of magnetic resonance (MR) imaging in patients with newly diagnosed asymptomatic multiple myeloma. PATIENTS AND METHODS: Thirty-eight consecutive patients with asymptomatic myeloma of low tumor mass and negative skeletal surveys underwent MR imaging of the thoracic and lumbosacral spine. The presence and patterns of marrow involvement were correlated with standard laboratory parameters and time to disease progression. RESULTS: Nineteen patients (50%) had evidence of marrow involvement at spinal MR imaging. MR patterns of marrow involvement were classified as diffuse (five patients), variegated (nine), and focal (five). Patients with abnormal MR imaging studies required therapy after a median of 16 months, versus 43 months for those with normal MR studies (P < .01). CONCLUSION: Abnormal marrow patterns were present in half of patients with asymptomatic myeloma. An abnormal MR study of the spine identified asymptomatic patients who were likely to require treatment earlier than those with a normal MR study. A normal MR pattern provided additional justification to defer institution of chemotherapy. However, MR imaging remains an investigational tool to stage patients with multiple myeloma until more data are accumulated. PMID- 7799026 TI - Ciprofloxacin versus trimethoprim/sulfamethoxazole for prophylaxis of bacterial infections in bone marrow transplant recipients: a randomized, controlled trial. AB - PURPOSE: To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. PATIENTS AND METHODS: Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day). Subjects were stratified before randomization according to tumor and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever, signs or symptoms of infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) to > or = to 400/microL. RESULTS: Seventy five CIP recipients and 71 TMS recipients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, or overall infection rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = .43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients (P = .001). Four infections caused by gram negative bacilli, including one bacteremia, occurred in TMS recipients versus none in CIP recipients (P = .06). No differences were noted in the incidence of rash or organ toxicity. TMS recipients had longer durations of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients (P = .08 for both comparisons). Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis. CONCLUSION: CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point. TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli, as well as a trend toward prolongation of granulocytopenia. PMID- 7799028 TI - Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sezary syndrome. AB - PURPOSE: To investigate the efficacy of combined topical therapy and systemic interferon alfa-2a in patients with mycosis fungoides (MF) and the Sezary syndrome (SS). PATIENTS AND METHODS: Between December 1987 and April 1993, 39 patients with all stages of MF and SS were treated with combined phototherapy and systemic interferon alfa-2a as part of two institutional studies. The initial phase I study of 15 patients established the maximum-tolerated dose of interferon and has been previously reported. Subsequently, 24 patients have been entered onto a phase II trial. Long-term follow-up data are provided for both studies. RESULTS: The median follow-up duration for the entire cohort is 28 months. Patients with all stages of disease were enrolled (stage IB, n = 14; IIA, n = 5; IIB, n = 6; III, n = 8; IVA, n = 5; IVB, n = 1). Thirty-four patients had received previous therapy. Overall, 36 of 39 patients achieved a complete response (CR; 62%) or partial response (28%) to therapy. The median response duration is 28 months (range, 1 to 64). Twenty-nine of 39 patients are alive, with a median survival duration of 62 months (range, 1 to 66). CONCLUSION: Interferon alfa-2a combined with phototherapy is an effective, safe, durable therapy for MF and SS. PMID- 7799029 TI - Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. AB - PURPOSE: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP) induced neurotoxicity. PATIENTS AND METHODS: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment. RESULTS: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH. CONCLUSION: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs. PMID- 7799030 TI - Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan. AB - PURPOSE: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma. We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity. PATIENTS AND METHODS: Nineteen patients with extremity melanoma (n = 16) or sarcoma (n = 3), underwent 90-minute ILP with TNF-alpha, interferon gamma (0.2 mg), and M (10 to 13 mg/L of limb volume) (TNF/IFN/M) (n = 12), or M alone (n = 7). Continuous intraoperative monitoring (CIM) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin. Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay. RESULTS: Systemic leaks > or = 1% from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone. Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak (> or = 1%) and zero of six patients without a leak (< 1%). These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak (2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL, respectively; P < .05). All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 (IL-6) levels than in patients with M alone (12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL, respectively; P < .001). Intracellular adhesion molecule (ICAM), IL-8, and TNF-R levels were also increased after ILP with TNF/IFN/M. CONCLUSION: ILP with TNF/IFN/M can be safely performed, as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit. Patients with a measured leak of > or = 1% develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks. PMID- 7799032 TI - Treatment of testicular cancer and the development of secondary malignancies. AB - PURPOSE: Secondary neoplasia represents one of the worst possible long-term complications of therapy for testicular cancer, frequently leading to death in patients cured of the primary malignancy. The frequency and importance of secondary malignant disease will be reviewed. METHODS: The international literature was screened for reports concerning secondary solid cancers or leukemias in patients treated with chemotherapy or radiotherapy for malignant germ cell tumors. RESULTS: Patients with testicular germ cell tumors appear to have a twofold significantly increased risk (range, 0.7 to 3.4) for the development of secondary neoplasia. Apart from contralateral testicular cancers, which are not treatment-related, a largely elevated inherited risk for secondary cancers in patients with germ cell tumors seems unlikely. Radiotherapy is associated with a two- to threefold increased risk for secondary solid tumors (range, 1.3 to 7.5). A three- to sevenfold increased risk seems to exist for the development of solid tumors arising in the previous irradiation ports, such as stomach, pancreatic, bladder, and renal cell cancer, and sarcomas. To date, no significantly elevated risk for secondary solid tumors was observed after chemotherapy, even including regimens with alkylating agents, eg, cisplatin and ifosfamide. However, the risk associated with chemotherapy needs to be reexamined when the median follow-up of studies will exceed more than 10 years. An increased relative risk for secondary leukemias after chemotherapy (range, 1.3 to 3.4) has been reported in three of eight studies with more than 300 patients. Four large studies indicate a significantly elevated risk (range, 15 to 25) for the use of conventional-dose etoposide (< 2 g/m2 cumulative dose); however, with a 5-year cumulative incidence of less than 0.5% of all patients, this risk seems small. Concerning high-dose etoposide regimens (> 2 g/m2), further studies are necessary. CONCLUSION: Treatment for testicular cancer is associated with a small, but clearly identifiable, risk for secondary solid tumors that can be attributed to radiotherapy, and for secondary leukemia mainly associated with the use of chemotherapy. The frequency of secondary neoplasia observed is rather low, and in the light of the high cure rate, the risk for the individual patient appears negligible and should not alter current treatment strategies for metastatic testicular cancer. PMID- 7799031 TI - Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. AB - PURPOSE: A minority of patients with poorly differentiated carcinoma achieve a complete response to cisplatin therapy. Recently, specific chromosomal abnormalities have been described for several solid tumor malignancies. Molecular and cytogenetic techniques were used to study tumors of patients with midline carcinoma of unknown primary site. MATERIALS AND METHODS: Forty patients with poorly differentiated carcinoma of unknown primary site had fresh tumor samples studied by cytogenetic analysis, Southern blot analysis for 12p copy number, and fluorescence in situ hybridization (FISH) for the identification of i(12p) and chromosome 12 aneuploidy. The response to cisplatin therapy was correlated to the diagnosis provided by the genetic studies. RESULTS: In 17 (42%) patients, a diagnosis was suggested by the genetic studies. This included a germ cell tumor in 12 (30%) patients by the finding of i(12p), increased 12p copy number, or a deletion of the long arm of chromosome 12. In five patients, a specific diagnosis other than germ cell tumor was suggested by tumor karyotype. These were neuroepithelioma, lymphoma, desmoplastic small-cell tumor, melanoma, and clear cell sarcoma. The 75% response proportion to cisplatin therapy in patients with tumors showing chromosome structural abnormalities of germ cell tumor was greater than the 18% response proportion in patients for whom no diagnosis was provided (P = .002). CONCLUSION: Molecular and cytogenetic studies are useful in establishing specific diagnoses in patients with poorly differentiated carcinomas of unknown primary site. This group of tumors is heterogeneous and is composed of germ cell tumors, melanoma, lymphoma, neuroepithelioma, and desmoplastic small round-cell tumor in addition to some that are not yet classifiable. Response to cisplatin therapy correlates with the finding of i(12p) in tumor by either molecular or cytogenetic studies. PMID- 7799033 TI - The eligibility of women for clinical research trials. PMID- 7799034 TI - The role of the American Society of Clinical Oncology in cancer control worldwide. PMID- 7799035 TI - Prognostic factors in bladder cancer after primary M-VAC. PMID- 7799038 TI - Radiation-recall dermatitis in a patient treated with paclitaxel. PMID- 7799036 TI - Multidrug-resistance modulation in metastatic breast cancer patients. PMID- 7799037 TI - Life-threatening hyperleukocytosis and pulmonary compromise after priming with recombinant human granulocyte-macrophage colony-stimulating factor in a patient with acute myelomonocytic leukemia. PMID- 7799039 TI - Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organization for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. Cooperating Investigators. AB - PURPOSE: To investigate whether treatment with prolonged low-dose adjuvant chemotherapy could improve survival of patients with axillary node-positive breast cancer. PATIENTS AND METHODS: Four hundred fifty-two patients with axillary node-positive breast cancer who received postoperative irradiation were prospectively randomized in a trial (European Organization for Research and Treatment of Cancer [EORTC] 09771) that compared surgery followed by prolonged low-dose chemotherapy versus surgery alone. Chemotherapy was given for a period of 2 years and consisted of monthly courses of cyclophosphamide 50 mg/m2 orally on days 1 to 14, methotrexate 15 mg/m2 intravenously on days 1 and 8, and fluorouracil 350 mg/m2 intravenously on days 1 and 8 (CMF). RESULTS: At a median follow-up time of 10 years, the overall survival duration was significantly prolonged in the chemotherapy arm (hazards ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = .04). Ten-year overall survival rates (+/- SE) were 59% (+/- 3.6%) for the chemotherapy arm and 50% (+/- 3.7%) for the control arm. Time to local relapse was significantly prolonged in the chemotherapy arm (hazards ratio, 0.63; 95% confidence interval, 0.42 to 0.94; P = .02). Patients with one to three positive axillary nodes and patients with estrogen receptor-negative tumors especially benefited from chemotherapy. Toxicity was observed in 93% of patients. CONCLUSION: We conclude that prolonged low-dose adjuvant CMF can significantly prolong overall survival in patients with node-positive breast cancer. However, considering the fact that toxicity was still considerable despite reducing the dose of chemotherapy by 50%, we believe that conventionally dosed short-term regimens are preferable in the treatment of node-positive breast cancer. PMID- 7799041 TI - Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy. AB - PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated. PMID- 7799040 TI - Very low-dose warfarin prophylaxis to prevent thromboembolism in women with metastatic breast cancer receiving chemotherapy: an economic evaluation. AB - PURPOSE: A recent double-blind, randomized trial demonstrated that very low-dose warfarin (VLDW) reduced the incidence of venous thromboembolism (VTE) without increasing the rate of bleeding in women with metastatic breast cancer receiving chemotherapy. We have evaluated the economic impact on the health care system of using VLDW in such patients. METHODS: The records of patients entered onto the trial and a simultaneous, fully allocated, costing model for a tertiary care hospital in Hamilton, Canada were used to determine the difference in costs associated with the care of patients with and without VLDW. RESULTS: The cost of providing VLDW was $ 21,854 (Canadian dollars) per 100 patients. This therapy led to a reduction in costs of $ 24,297 per 100 patients, thus saving the health care system $ 2,443 per 100 patients. In the sensitivity analysis, VLDW prophylaxis still did not increase health care costs unless the cost of VLDW was greatly increased, the cost of treating thromboembolic episodes was markedly reduced, or the incidence of either VTE or bleeding with VLDW was increased above the rates observed in the trial. CONCLUSION: We conclude that for women receiving chemotherapy for metastatic breast cancer, the benefits of VLDW can be realized without increased health care costs. PMID- 7799042 TI - Is bigger better? PMID- 7799043 TI - Pepsinogen C is a new prognostic marker in primary breast cancer. AB - PURPOSE: Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS: Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS: A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION: Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution. PMID- 7799044 TI - Cured of breast cancer? AB - PURPOSE: That patients can be ultimately cured of breast cancer has been questioned, because late deaths from the disease have been observed even several decades after the diagnosis. The purpose of this study was to investigate late mortality caused by breast cancer. PATIENTS AND METHODS: Using the files of local hospitals and the Finnish Cancer Registry, we identified all patients with histologically diagnosed invasive breast cancer in a defined urban area (city of Turku, Finland) from 1945 to 1969 (n = 601). In 563 cases (94%), clinical data and histologic and autopsy slides could be reviewed, and these women had been monitored for a median of 29 years (range, 22 to 44; n = 66) or until death (n = 497). RESULTS: Mortality from breast cancer was observed even during the fourth follow-up decade, but if women who were diagnosed with contralateral breast cancer were excluded (n = 30), no deaths from breast cancer were identified after the 27th year of follow-up evaluation. The 30-year survival rates were 62% (95% confidence interval [CI], 54% to 70%), 19% (95% CI, 13% to 25%), and 0% for women with pN0 (node-negative) and pN1 or pN2 (node-positive) disease, respectively. High 30-year survival rates were found in small (pT1N0M0) unilateral cancers (80% alive; 95% CI, 66 to 94%), and in the lobular (45% alive; 95% CI, 31% to 59%) and the special histologic types (81% alive; 95% CI, 67% to 95%). These survival rates were obtained when correcting either for known intercurrent deaths or for mortality in the age- and sex-matched general population. CONCLUSION: Breast cancer, node-negative and node-positive, may be permanently cured even if treated with locoregional therapy only. The survival figures listed here may be considered as minimum values, because women with breast cancer diagnosed in the same area from 1970 to 1984 showed significantly improved short-term (< 20 years) survival rates over those diagnosed from 1945 to 1969. PMID- 7799045 TI - Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. AB - PURPOSE: To determine the prognostic value of immunostaining of P-glycoprotein (P gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS: Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS: P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION: Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy. PMID- 7799047 TI - Oligometastases. PMID- 7799046 TI - Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial. AB - PURPOSE: Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS: One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS: Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION: rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended. PMID- 7799048 TI - Geographic, age, and racial variation in the treatment of local/regional carcinoma of the prostate. AB - PURPOSE: Prostate cancer is one of the most common cancers in men. Incidence rates increase with age and are substantially higher in black men than white men. This study examines the variations in the use of radical prostatectomy and radiation by geographic area, age, and race. MATERIALS AND METHODS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End-Results Program (SEER) were used to examine treatment differences. Current treatments generally consist of prostatectomy, radiation, or careful observation for clinically localized or regional disease. RESULTS: The age-adjusted proportion of men, age 50 and older, who received radical prostatectomy increased sharply between 1984 and 1991, from 11.0% to 32.3% among men with local/regional disease. The choice of treatment varied widely by geographic regions. In 1991, the proportion that received prostatectomy was highest in Utah (47.8%) and lowest in Connecticut (22.5%) among men with localized and regional disease. The increase in radical prostatectomy was not limited to younger men. Although the rates increased for blacks, black men had lower age-adjusted rates of prostatectomy than whites in all years of the study. CONCLUSION: The SEER data show a clear trend toward more aggressive treatment, especially prostatectomy. However, the proportion of black men who received prostatectomy was substantially lower than that of white men and this disparity does not appear to be changing. PMID- 7799049 TI - Staphylococcal infections. Proceedings of an advisory workshop. Boston, September 11-12, 1993. PMID- 7799050 TI - Nasal and hand carriage of Staphylococcus aureus in healthcare workers. AB - Six double-blind, randomised placebo-controlled clinical trials in the United States have evaluated the elimination of Staphylococcus aureus carriage in healthcare workers with mupirocin ointment. Consistent data from the six centres demonstrated that calcium mupirocin ointment administered intranasally for five days is safe and effective in eliminating nasal carriage of S. aureus. Hand cultures were also performed at one centre, showing that hand carriage rates were significantly decreased 72 hours post-therapy and at six months. Additionally, molecular typing of all isolates obtained from the nares and hands found identical strains at both sites in the majority of subjects, implicating the nares as the primary reservoir of S. aureus colonisation. PMID- 7799051 TI - Staphylococcus aureus infection in haemodialysis patients. Mupirocin as a topical strategy against nasal carriage: a review. AB - Staphylococcus aureus is isolated from 42% of the bacteraemic episodes occurring in haemodialysis patients. Several epidemiological studies indicate that nasal carriage of S. aureus is of pivotal importance in determining the risk of subsequent infections by this micro-organism in haemodialysis patients. First, nasal carriage is prevalent in about 42% of these patients, this high rate being observed from the onset of maintenance dialysis therapy. Second, there is a significant relationship between nasal and hand carriage of the organisms. Third, there is usually a similarity between infecting S. aureus strains and those isolated from nasal surveillance cultures obtained from the same patient. The nares are therefore an elective site for the prevention of S. aureus infections in haemodialysis patients; this was shown with oral rifampin. The studies demonstrating the effectiveness of nasal mupirocin for this indication are summarised. The need for continued chemosuppression with maintenance application (e.g. once per week) is underscored. Such a long-term application of nasal mupirocin in haemodialysis patients with nasal carriage is very cost-effective and is only very rarely associated with the emergence of mupirocin resistance in S. aureus. PMID- 7799052 TI - Cost-effectiveness of antibiotic prophylaxis of wound infection. AB - The estimated cost of a wound infection can vary substantially between countries and is dependent not only on the type of surgery performed, but also on varying medical practices and differing accounting methods. We therefore devised a flexible method to compare the cost-effectiveness of different antibiotic prophylactic regimens. Taking into account drug cost and the difference in infection rate between regimens, for any given wound infection cost, the analysis can indicate which regimen is most appropriate. PMID- 7799053 TI - Cost-containment using an outcome-based best practice model for the management of MRSA. AB - Prior to 1991, most patients at Christ Hospital and Medical Center from whom methicillin-resistant Staphylococcus aureus (MRSA) was cultured were isolated and treated with systemic antibiotics, irrespective of whether they were colonised or infected. The result of this practice was a confused, un-coordinated approach to the management of MRSA patients with a negative effect on the quality and cost of patient care. An interdisciplinary team set about developing and implementing a Best Practice Guideline over the years 1991 and 1992. This guideline provided a separate approach to infected and colonised patients. This intervention led to a decreased average length of stay in hospital of over 10 days, a reduction in the readmission rate of these patients from 8.7% in 1990 to 2.7% in 1992, and resulted in total cost savings of over $1.9 million. PMID- 7799054 TI - The choice of empirical antibiotic therapy for nosocomial pneumonia. AB - Nosocomial pneumonia has the highest crude mortality rate of all hospital acquired infections. The choice of empirical antibiotic therapy can be based on in vitro sensitivities of sputum bacterial isolates. Organisms recovered from purulent sputum of 500 intensive care unit (ICU) patients from five hospitals in Louisville, Kentucky, had antibiotic sensitivities measured by microbroth dilution. The most common isolates were Staphylococcus aureus (26.6%), Pseudomonas species (24.8%), Enterobacter species (11.8%), Escherichia coli (7.2%), Klebsiella species (7.0%), Streptococcus species (4.4%) and Serratia species (4.0%). These organisms were tested for susceptibility to amikacin, ciprofloxacin, imipenem/cilastatin, ticarcillin/clavulanate, piperacillin, ceftriaxone and ceftazidime. The antibiotics effective against more than 80% of the seven most common isolates included amikacin (97%), imipenem (94%), ciprofloxacin (92%) and ticarcillin/clavulanate (84%). These sensitivity patterns may serve as a guide to choosing empirical antibiotics for ICU-acquired pneumonia in Louisville. When the use of a beta-lactam antibiotic alone or in combination with an aminoglycoside is preferred, imipenem or ticarcillin-clavulanate may be considered the antibiotics of choice. Studies are in progress to delineate the clinical use of ciprofloxacin alone or in combination with beta-lactam antibiotics for treating nosocomial pneumonia. PMID- 7799056 TI - Epidemiology of staphylococcal infections--a USA perspective. AB - Data collected from the National Nosocomial Infection Surveillance show that Gram positive organisms, and Staphylococcus aureus in particular, are a major cause of nosocomial infections, especially wound infections, pneumonia and bacteraemia. Currently in the United States, approximately 18% of S. aureus isolates show intrinsic resistance to methicillin. PMID- 7799055 TI - The efficacy of amoxycillin/clavulanate (Augmentin) in the treatment of severe staphylococcal infections. AB - The experimental and clinical values of amoxycillin/clavulanate in severe Staphylococcus aureus infections are reviewed. Experimentally, amoxycillin/clavulanate was highly effective in the treatment of acute endocarditis due to methicillin-sensitive isolates of S. aureus (MSSA) in rats. In addition, high doses of amoxycillin/clavulanate also cured experimental endocarditis due to methicillin-resistant strains of S. aureus (MRSA) in the animal model. In the clinical setting, a review of 86 patients with either community- or hospital-acquired bacteraemia due to MSSA showed that intravenous treatment with amoxycillin/clavulanate was adequate for empirical (and apparently also long-term) therapy of such severe infections. However, the retrospective nature of the analysis did not allow assessment of the relative efficacy of amoxycillin/clavulanate as compared with standard anti-staphylococcal drugs, such as flucloxacillin or vancomycin. Further prospective studies are warranted to address this issue. Thus, amoxycillin/clavulanate appears to be a good candidate for empirical treatment of severe infections that may be caused by MSSA. Usage of amoxycillin/clavulanate against MRSA is, however, still experimental and is not currently advocated for the treatment of MRSA infections in humans. PMID- 7799057 TI - Epidemiology of staphylococcal infections--a European perspective. AB - Multiple resistant staphylococci are a major health concern worldwide. In Europe, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) differs widely between countries in the south and those in the north. In The Netherlands, which has one of the lowest rates of MRSA infection in Europe, stringent infection control measures are in place which include the isolation of all carriers and the treatment of patients and staff carriers with mupirocin. PMID- 7799059 TI - Image registration of SPECT and CT images using an external fiduciary band and three-dimensional surface fitting in metastatic thyroid cancer. AB - Image registration of 131I SPECT with CT scans was performed in a patient with metastatic thyroid carcinoma using an external fiduciary band and a three dimensional surface-fitting algorithim. Areas of metastatic disease taking up 131I were accurately localized to the liver, lungs and vertebral bodies; providing information that could not be obtained by planar or SPECT images alone. Based on these findings, further invasive diagnostic procedures were not performed, therefore considerably altering management in this patient. This approach to image registration has immediate clinical utility in the registration and interpretation of SPECT studies with corresponding CT or MRI scans. PMID- 7799058 TI - Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma. AB - METHODS: The results of in vivo somatostatin scintigraphy were correlated with those of MIBG from 14 patients, aged 22-66 yr, with metastatic pheochromocytoma (10 patients), malignant paraganglioma (3 patients) and metastatic ganglioneuroblastoma (1 patient). Twelve patients had elevated catecholamine excretion. A dynamic study and serial whole-body scans (4-48 hr) were obtained after injection of 130-187 MBq of 111In-DTPA-Phe-1-octreotide. When indicated, SPECT imaging was done. The results were compared to MIBG scans obtained after a diagnostic or a therapeutic dose. RESULTS: Three patients with more than 20 tumor sites on MIBG scans had only 1-9 sites on 111In-octreotide scintigraphy. Two patients had no MIBG uptake but one had lung uptake on octreotide scintigraphy. In the other 9 patients with a total of 41 foci of MIBG uptake, 33 sites of 111In octreotide uptake are found. All positive images with octreotide scintigraphy were seen at or before 4 hr, but the contrast improved at 24 hr. Uptake intensity was lower with 111In-octreotide than MIBG and the number of tumor sites was higher with MIBG. However, seven foci were positive only on octreotide scintigraphy and six of them could not be confirmed by other imaging modalities. CONCLUSION: Use of octreotide to identify somatostatin receptors seems promising, especially when results from MIBG scans are negative. Moreover octreotide images could aid in determining a treatment regimen as well as establishing the extent of disease and prognosis. PMID- 7799060 TI - Positional biliary stasis: scintigraphic findings following biliary-enteric bypass surgery. AB - Hepatobiliary scintigraphy has proven to be a reliable noninvasive imaging modality to evaluate postoperative biliary obstruction, which is a frequent complication following biliary enteric bypass surgery. We present a case of a patient who had biliary enteric bypass surgery with a scintigraphic pattern simulating partial obstruction on a 99mTc hepatobiliary study performed with the patient in a supine position. The biliary stasis seen in the supine images disappeared almost completely when the images were repeated after 30 min in an upright position. Progressive accumulation of activity initially seen in the region of the biliary enteric anastomosis was not present 3 days later on a repeat study with the patient in an upright position, confirming that biliary stasis in this patient was due to a positional phenomenon. This case illustrates that biliary stasis may be positional in nature. Position related stasis should be a consideration when interpreting hepatobiliary scintigraphic studies in postoperative patients and when suspected, patients should be imaged in the upright position. PMID- 7799061 TI - Thallium-201 uptake in eosinophilic granuloma of the frontal bone: comparison with technetium-99m-MDP imaging. AB - An 11-yr-old female presented with a 6-wk history of left upper lid tenderness and left eye lacrimation. Left lateral supraorbital mass and left preauricular lymph node were the only significant physical examination findings. On skull x ray, a left frontal bone defect was noted. CT and MRI showed a soft-tissue mass in the area of the bone defect. Bone scintigraphy exhibited peripheral uptake within the central photon deficient area. With 201TI SPECT, high uptake was noted on early and delayed images. Diagnosis of eosinophilic granuloma was performed by biopsy. Since thallium uptake was seen in the area where photon deficiency was exhibited by 99mTc-MDP scintigraphy, we speculate that thallium SPECT could detect eosinophilic granuloma when radiographic skeletal survey or radionuclide bone scan are equivocal. It could also rule out multiple bone involvement and recurrence or regrowth after therapy. PMID- 7799062 TI - Myocardial clearance kinetics of technetium-99m-teboroxime following dipyridamole: differentiation of stenosis severity in canine myocardium. AB - The purpose of the current study was to determine whether teboroxime clearance kinetics are useful in differentiating the severity of coronary artery flow restriction. METHODS: Groups of dogs received stenoses of the left circumflex coronary artery as follows: nine dogs received a mild-to-moderate stenosis (Group 2) and eleven dogs received severe stenoses (Group 3). In three control dogs (Group 1), there was no stenosis. Using miniature cadmium-telluride radiation detectors, myocardial teboroxime activities were continuously monitored in both the control and stenosed zones following dipyridamole infusion. RESULTS: A significant difference in fractional myocardial clearance between the control zones (0.69 +/- 0.01, n = 26) versus mild-to-moderate (0.61 +/- 0.06, p < 0.05, n = 9) and severe (0.57 +/- 0.03, p < 0.01 versus control, p < 0.05 versus mild-to moderate, n = 11) flow-restricted zones was observed over a 1-hr period. Significant differences between normal and both stenosed zones became apparent after 7 min of clearance. Significant differences in myocardial clearance between mild-to-moderate and severe groups were detected within 15 min. CONCLUSION: Thus, in this canine model using dipyridamole, miniature probe-determined teboroxime myocardial clearance can differentiate among normal myocardium, myocardium distal to a mild-to-moderate stenosis and myocardium distal to a severe stenosis. PMID- 7799063 TI - Myocardial clearance kinetics of technetium-99m-teboroxime following dipyridamole injection. PMID- 7799064 TI - Assessment of scatter components in high-resolution PET: correction by nonstationary convolution subtraction. AB - This paper describes a new approach to determine individual scatter kernels and to use them for scatter correction by integral transformation of the projections. METHODS: Individual scatter components are fitted on the projections of a line source by monoexponentials. The position-dependent scatter parameters of each scatter components are then used to design non-stationary scatter correction kernels for each point in the projection. These kernels are used in a convolution subtraction method which consecutively removes object, collimator and detector scatter from projections. This method is based on a model which assumes that image degradation results exclusively from Compton interactions of annihilation photons, thus neglecting further Compton interactions of object scatters with collimator and detector. RESULTS: Subtraction of the object scatter component improved contrast typical of what is obtained with standard convolution subtraction methods. The collimator scatter component is so weak that it can be safely combined with object scatter for correction. Subtraction of detector scatter from images did not improve contrast because statistical accuracy is degraded by removing counts from hot regions while cold regions (background) remain unchanged. CONCLUSION: Subtraction of object and collimator scatter improves contrast only. The slight gain in image sharpness resulting from the subtraction of detector scatter does not justify removal of this component at the expense of sensitivity. PMID- 7799066 TI - Scattered photons as "good counts gone bad:" are they reformable or should they be permanently removed from society? PMID- 7799065 TI - Radiolabeled octreotide for the demonstration of somatostatin receptors in malignant lymphoma and lymphadenopathy. AB - This prospective study evaluated somatostatin receptor-specific scintigraphy as a clinical tool for routine detection of malignant lymphoma. METHODS: Forty-one consecutive patients were examined using 111In-DTPA-D-Phe-1-octreotide. Thirty four patients had diagnoses of Hodgkin's disease (n = 11) or non-Hodgkin's lymphoma (n = 23) previously verified and staged by hematology, histology and imaging methods (CT, chest x-ray and abdominal ultrasonography). The remaining seven patients initially suspected of presenting lymphoma (n = 5) or lymphoma recurrence after chemotherapy and radiotherapy (n = 2) were subsequently shown to have other diseases. Planar images were recorded 4, 24 and 48 hr after intravenous injection and evaluated without knowledge of other results. In case of negative planar scintigraphy, additional SPECT images were obtained. Since these failed to increase sensitivity, they were omitted after 15 negative recordings. RESULTS: Octreotide scintigraphy did not yield false-positive results. The sensitivity for detecting Hodgkin's disease was 70% and varied from 88% in the neck and chest to 13% in the abdomen and pelvis. The sensitivity for non-Hodgkin's lymphoma was not influenced by localization and amounted uniformly to 35% but varied with the degree of malignancy between 44% (high-grade) and 29% (low-grade malignancy). CONCLUSION: Our results suggest that radiolabeled octreotide is better suited to characterize somatostatin receptor expressing lymphomas than to localize lesion sites. It is useful for imaging Hodgkin's disease, especially above the diaphragm. PMID- 7799067 TI - A study of the liver-heart artifact in emission tomography. AB - With the introduction of 99mTc-teboroxime, a previously undocumented artifact has shown up in cardiac SPECT imaging. In the images, the uptake values near the inferior wall are lower than expected. The artifact has been reported in the literature, but an adequate explanation has not yet been provided. The high uptake of 99mTc-teboroxime in the liver has been demonstrated to be the cause of this artifact. METHODS: With simulations we show that an artifact can be reproduced by applying filtered backprojection (without corrections for attenuation) of attenuated and blurred projections. The conclusions from the simulations are validated with SPECT and PET phantom measurements. Maximum likelihood expectation maximization (ML-EM) reconstruction is applied to evaluate the effect of accurate attenuation correction. The influence of the high liver uptake on the convergence of ML-EM was also evaluated. RESULTS: The artifact results mainly when the photon attenuation during reconstruction is ignored. This results in a distorted reconstruction of the liver. These distortions affect the neighboring inferior wall of the myocardium. While the use of opposite projections reduces the effect, accurate attenuation correction nearly eliminates it. A small additional deformation is caused by the position dependence of the spatial resolution of the gamma camera. It was also noted that the presence of the liver slows down the convergence of ML-EM in the heart region. CONCLUSION: The liver-heart artifact is an attenuation effect and is eliminated by attenuation correction. The local convergence of ML-EM is affected by the total image content. PMID- 7799069 TI - Estimating the diagnostic yields resulting from renography and deconvolution parameters: a logistic regression analysis. AB - METHODS: Seventy patients with established diagnoses of normal, parenchymally insufficient or acutely obstructed kidneys were subjected to gamma camera renography. Deconvolution was then performed using three main techniques subdivided into six variants. Parameters from time-activity curves as well as retention curves were calculated. Logistic regression analysis was performed to assess the ability of renography and deconvolution methods to differentiate between kidney groups. RESULTS: Discrimination between the groups was achieved by standard renography using six of 17 tested renogram parameters. Based on a set of six curve parameters, the correct classification rates ranged 86%-100%. Five of the six variants of the deconvolution technique used produced similar results. None, however, produced results which were as robust as those from renography. The sixth deconvolution method was consistently worse than the others. CONCLUSION: Standard renography was consistently better than any of the deconvolution techniques used in the separation of the kidney groups. Conceptually, the results of a logistic regression analysis of renogram parameters may raise possibilities in the field of computer-aided diagnosis. PMID- 7799068 TI - Canine myocardial beta-adrenergic, muscarinic receptor densities after denervation: a PET study. AB - In an effort to better understand cardiac neurotransmission, PET was serially used in dogs to assess changes in ventricular muscarinic (MR) and beta-adrenergic receptor (beta-AR) densities following chemical or surgical denervation. METHODS: Beta-adrenergic and MR receptor concentrations were studied in beagle dogs nine days after chemical sympathectomy (using the neurotoxin 6-hydroxydopamine) or 3-7 wk and 23-28 wk after surgical intrapericardial denervation. RESULTS: In control dogs (n = 13), global beta-AR and MR concentrations were 32 +/- 4 and 62.2 +/- 10.4 pmole/ml tissue, respectively. Nine days after 6-hydroxytk; 1opamine (n = 8), hemodynamic tests and MIBG scintigraphy demonstrated the destruction of cardiac sympathetic innervation. Beta-adrenergic density increased by 190% (p < 0.001) while MR density remained unchanged. Three to 7 wk after surgery (n = 5), hemodynamic tests and MIBG scintigraphy demonstrated both parasympathetic and sympathetic denervations. Beta-adrenergic density was increased by 219% while MR concentration remained unchanged. Twenty-three to 28 wk after surgery, atrial innervation was restored (hemodynamic tests) while ventricular sympathetic innervation was not (MIBG scintigraphy). Beta-adrenergic density remained high. CONCLUSION: The present study demonstrates the ability of PET to serially assess myocardial receptor concentrations. The absence of change in MR density and the prolonged up-regulation of beta-AR following heart denervation are the main findings of the present study. PMID- 7799070 TI - Quantitative myocardial mapping of perfusion and metabolism using parametric polar map displays in cardiac PET. AB - Most efficacy studies of cardiac PET in demonstrating myocardial ischemia and viability have been performed using one or more transversal static images of the heart. In contrast, in this paper we describe a method of functional imaging of the complete left ventricular myocardium for perfusion with nitrogen-13-ammonia, both at rest and during a dipyridamol stress test, and of glucose metabolism with 18F-fluorodeoxyglucose (18FDG). METHODS: This was performed by using the data of each of 48 radial segments of 10 short-axis images as tissue data and LV cavity data of three basal planes as blood pool data. The study describes the results of 19 normal volunteers and 36 patients with coronary artery disease. From the data of the normal volunteers a 95% normal confidence interval was calculated for each imaging modality. These intervals were then used to describe the patient data as normal, ischemic or infarcted. RESULTS: The results of analysis of the parametric images was compared with the results of static analysis of the same patient data and found to be less dependant on the detection threshold used. CONCLUSION: The described method enables the routine application of functional PET imaging of the total myocardium by the semi-automatic construction of parametric flow and metabolism polar maps. It thus provides an increased performance in the diagnosis, quantification and localization of myocardial ischemia and viability over conventional PET imaging. PMID- 7799071 TI - PET versus SPECT in distinguishing radiation necrosis from tumor recurrence in the brain. AB - Two cases of postsurgical brain tumor evaluation in which MRI was inconclusive are discussed. Functional imaging techniques, such as FDG-PET and 201TI SPECT, were used in both cases for distinguishing radiation necrosis from tumor recurrence. These methods proved to be complimentary. For Patient 1, FDG-PET showed more limitations compared to 201TI SPECT. FDG-PET results on the other hand, were consistent with the final diagnosis and the SPECT image was false positive for tumor recurrence in Patient 2. PMID- 7799072 TI - Will the nuclear medicine industry survive? PMID- 7799073 TI - Winter summit to discuss current crisis in nuclear medicine. PMID- 7799074 TI - Somatostatin receptor-based imaging in malignant lymphomas. PMID- 7799075 TI - Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma. AB - The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with 131I of differentiated thyroid carcinoma. METHODS: A total of 814 females of child-bearing age were studied. The fertility of 627 females who received 131I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with 131I with an internal control group, as well as with local population incidence. RESULTS: There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a women treated with 131I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with 131I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. CONCLUSION: The risk of long-term effects of 131I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence. PMID- 7799076 TI - Smithsonian documents history of PET. PMID- 7799077 TI - How safe for the patient is iodine-131 therapy for differentiated thyroid carcinoma? PMID- 7799078 TI - Phosphorus-32-chromic phosphate for ovarian cancer: I. Fractionated low-dose intraperitoneal treatments in conjunction with platinum analog chemotherapy. AB - For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed. METHODS: In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle. RESULTS: There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%. CONCLUSION: Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer. PMID- 7799079 TI - Planar and high-resolution SPECT bone imaging in the diagnosis of facet syndrome. AB - This study's goals were to determine the appearance of potentially symptomatic facet joints on planar and high-resolution SPECT radionuclide bone imaging, relate the relative sensitivity of the two techniques and assess the predictive value in a clinical setting. METHODS: Fifty-eight consecutive patients referred with a diagnosis of possible facet syndrome were imaged during the same visit using both a well-established planar and a SPECT technique developed to emphasize high spatial resolution. The standard of reference included facet injections with a marcaine and steroid mixture, with review of a pain journal completed by the patient included in the followup criteria. RESULTS: In the 43 patients comprising the final study group, 7 were diagnosed with facet syndrome, 5 with abnormal planar images and 7 with abnormal SPECT images. A total of 10 facet joints with abnormal increased uptake were seen on SPECT which were not demonstrated on planar imaging. There was high sensitivity (100% SPECT, 71% planar), but somewhat lower specificity (71% SPECT, 76% planar). The negative predictive value was high (100% SPECT, 93% planar). Radionuclide bone imaging additionally discovered a nonfacet joint etiology for patient symptoms in 16 of the 43 patients. CONCLUSION: Higher spatial resolution SPECT images are better accepted by referring physicians who correlate them with CT or MR images. The high negative predictive value allows radionuclide bone imaging to be used to select appropriate patients to undergo the invasive facet injection procedure. PMID- 7799080 TI - Choosing a strategy for the diagnostic management of suspected scaphoid fracture: a cost-effectiveness analysis. AB - To assess the cost-effectiveness of various strategies for the diagnostic management of clinically suspected scaphoid fracture, a decision-analytic model was built to evaluate three strategies and to compare them with a (clairvoyant) reference diagnostic management strategy. METHODS: Evaluated strategies were: (A) repeated radiography up to 2 wk; (B) repeat radiography up to 6 wk; and (C) radiography, followed by bone scintigraphy in patients with negative initial radiographs. Therapy consisted of 12 wk of immobilization for a radiographically or scintigraphically proven fracture. Diagnostic costs, therapeutic costs, period of immobilization and nonunion rate were calculated for all three strategies. Estimates were derived from a descriptive management study using bone scintigraphy and available literature. Sensitivity analyses were performed. RESULTS: Overall costs were 273.7, 317.7 and 316.1 European Currency Units (ECU) for Strategies A, B and C, respectively (1 ECU = 1.15 U.S. dollar). Strategy B led to the longest average period of immobilization (8.6 wk), while Strategy A resulted in the highest nonunion rate (4.7%). The costs per nonunion saved for the additional use of bone scintigraphy (Strategy C) was ECU 2618 when compared to Strategy A. CONCLUSION: The use of bone scintigraphy in the diagnostic management of scaphoid fractures is accurate, convenient for patients and cost effective. PMID- 7799081 TI - Diagnosis of scaphoid fractures: the role of nuclear medicine. PMID- 7799082 TI - Samarium-153-particulate hydroxyapatite radiation synovectomy: biodistribution data for chronic knee synovitis. AB - Biodistribution data for the radiation synovectomy agent samarium-153-particulate hydroxyapatite (153Sm-PHYP) are reported. METHODS: Mean extra-articular activity accumulation calculated from serial whole-body scans in 13 patients treated for chronic knee synovitis was 0.74% of injected activity (range 0%-3%). RESULTS: In four patients (31%), activity was noted in the lung (mean 0.68% of injected activity). In six patients (46%), 0.29% of injected activity accumulated in the regional lymph nodes and in three patients (23%), 0.62% of injected dose accumulated in the liver. Absorbed dose estimates were lung: 14 mGy, regional lymph nodes; 50 mGy, liver; 4 mGy. SPECT demonstrated good distribution of 153Sm PHYP throughout the anterior knee compartments, although distribution to the posterior compartment was variable. CONCLUSION: Distribution is dependent on adequate knee flexion immediately following injection and may be influenced by the size range of labeled particles. Favorable biodistribution data suggest that 153Sm-PHYP is a potentially useful radiation synovectomy agent. PMID- 7799084 TI - Perfusion and ventilation scans in patients with extensive obstructive airway disease: utility of single-breath (washin) xenon-133. AB - The presence of extensive obstructive airway disease in many patients leads to an interpretation of intermediate or indeterminate probability for pulmonary emboli using ventilation/perfusion lung scans. We observed that patients with extensive obstructive airway disease having perfusion abnormalities matching those on a single-breath xenon image usually have a normal pulmonary angiogram. This study's objective was to further assess the utility of a single-breath image in evaluating patients with extensive obstructive airway disease and abnormal perfusion studies categorized as having intermediate or indeterminate probability of pulmonary embolism in an attempt to decrease the number of nondiagnostic studies. METHODS: We studied retrospectively 33 patients with extensive obstructive airway disease, with abnormal perfusion scans and no infiltrates on chest x-ray categorized as having intermediate or indeterminate probability of pulmonary embolism. We established the presence or absence of matching ventilation and perfusion abnormalities by comparing perfusion scan and single breath images. RESULTS: Among 25 patients with perfusion abnormalities matching the initial ventilation pattern on single-breath images, only 1 (4%) had pulmonary emboli as documented by pulmonary angiogram. Four out of the remaining 8 patients with no matching perfusion and single-breath ventilation pattern had pulmonary emboli (50%). CONCLUSION: Patients categorized by ventilation/perfusion scintigraphy as having intermediate or indeterminate probability for pulmonary emboli due to the presence of extensive obstructive airway disease can be further subclassified using single-breath images. Patients with matching perfusion and single-breath ventilation pattern should be categorized as having low probability for pulmonary embolism, regardless of the extent of the ventilation abnormalities. PMID- 7799083 TI - Evaluation of technetium-99m-sestamibi lung uptake: correlation with left ventricular function. AB - Lung uptake of 201Tl is a reliable marker of left ventricular dysfunction. The goal of our study was to establish whether the evaluation of lung-to-heart uptake ratios (LHR) with 99mTc-sestamibi imaging may provide valuable information. METHODS: We studied 72 male subjects with recent anterior myocardial infarction undergoing 99mTc-sestamibi first-pass ventriculography and SPECT perfusion imaging. A group of 46 gender-matched subjects with low pre-test likelihood of CAD and normal exercise and rest 99mTc-sestamibi perfusion images was used as a control. The lung-to-heart count ratios (LHR) were calculated on planar projections from the sets of SPECT images. RESULTS: Both groups were studied at rest and after a symptom-limited exercise tolerance test. In the control group a significant decrease in LHR was observed during stress (p < 0.001). The infarcted group showed significantly higher LHR values both at rest and at stress. Exercise and rest LHR values did not differ significantly. A positive correlation was observed between LHR values and left ventricular ejection fraction at rest and stress. CONCLUSION: LHR, measured by 99mTc-sestamibi imaging, gives clinically useful information. Both resting and postexercise values are correlated with ejection fraction and should predict left ventricular dysfunction. PMID- 7799085 TI - Alveolar integrity in pulmonary emphysema using technetium-99m-DTPA and technetium-99m-HMPAO radioaerosol inhalation lung scintigraphy. AB - The alveolar integrity (AI) in 17 male patients with pulmonary emphysema (EMPH) diagnosed by chest x-ray was measured by 99mTc-DTPA and 99mTc-HMPAO radioaerosol inhalation lung scintigraphy. METHODS: The patients were divided into two groups: (A) nine patients with pulmonary emphysema and normal carbon monoxide diffusion capacity (DLCO) and (B) eight patients with pulmonary emphysema and abnormal DLCO. The degree of AI damage in EMPH was presented as the slope of the time activity curves from the dynamic left lung imagings in DTPA and HMPAO. The AI of EMPH patients were compared with the AI of 16 normal controls. RESULTS: The results show that: (1) the slope of DTPA is larger than that of HMPAO in each of the portions of the left lung for any of the study groups; (2) statistical differences were found between the normal controls and EMPH patients in HMPAO but not in DTPA; and (3) the correlation was not good between DLCO and DTPA/HMPAO in EMPH patients. CONCLUSION: Our results suggest that: (1) at least two different mechanisms in the lungs were at work; (2) the AI damage in EMPH developed mainly in the lipophilic part of the alveoli; and (3) the AI damage presented as slopes of DTPA/HMPAO in our study was different from the traditional pulmonary function such as DLCO. PMID- 7799086 TI - Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide. AB - METHODS: Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis. RESULTS: For midgut carcinoids, the tumor-to-blood ratio was 51:220, for medullary thyroid carcinoma 4:39, and for two endocrine pancreatic tumors 6 and 1500. Tumor-to-muscle ratios varied between 1 and 1200 and tumor-to-fat between 2 and 1500 depending on tumor type. CONCLUSION: The sometimes extremely high tumor-to-normal tissue ratios present the possibility for use of radiolabeled octreotide for radiation therapy of somatostatin receptor positive tumors. PMID- 7799087 TI - Effect of inhaled furosemide on lung clearance of technetium-99m-DTPA. AB - The diuretic furosemide has been reported to have a protective effect on allergic asthmatic reactions. This study was performed to investigate the effect of aerosolized furosemide on the lung clearance of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: Pulmonary clearance rates of 99mTc-DTPA were measured by a computerized gamma camera with and without the inhalation of aerosol furosemide in 6 nonsmoking normal volunteers (Group 1), 7 smokers without pulmonary disease (Group 2) and 11 patients with asthma (Group 3). RESULTS: None of the six normal volunteers showed significant effects of inhaled furosemide on the 99mTc-DTPA clearance rates. Three of seven smokers presented an accelerated 99mTc-DTPA clearance by inhaled furosemide and the other four showed no significant change of 99mTc-DTPA clearance by furosemide inhalation. However, in 10 of 11 patients with asthma, there was significant suppression of 99mTc-DTPA clearance by furosemide inhalation. CONCLUSION: Asthmatics possess a furosemide sensitive mechanism. Pulmonary aerosol scintigraphy with 99mTc-DTPA will be useful in predicting the effect of inhaled furosemide therapy. PMID- 7799088 TI - Myocardial blood flow: comparison of oxygen-15-water bolus injection, slow infusion and oxygen-15-carbon dioxide slow inhalation. AB - This study investigates the most appropriate protocol for measuring regional myocardial blood flow (MBF) using 15O-water in clinical applications. METHODS: Regional MBF, perfusable tissue fraction (PTF) and arterial blood volume (Va) were measured using 15O-water and dynamic PET on five healthy volunteers based on previously published models. Calculated values were compared for the following three tracer administration protocols: 15O-water bolus injection, 15O-water slow (2 min) infusion and 15O-carbon dioxide slow (2 min) inhalation. For the two slow administration protocols, the three parameters MBF, PTF and Va were computed by fitting the model equations to the myocardial regional time-activity curve. For the bolus injection of 15O-water, only two parameters, MBF and PTF, were fitted by using a fixed Va value obtained by a carbon dioxide blood volume scan. RESULTS: All protocols provided consistent MBF values, and the calculated values were homogeneous throughout the whole myocardial segments for all subjects. PTF values were also homogeneous and consistent in the anterior and lateral wall regions, but were significantly greater in the septum (approximately 20%) when the slow 15O-carbon dioxide inhalation protocol was used. MBF and PTF values obtained from the bolus injection protocol showed the smallest intersubject and interregional variations. The simulation study also showed that the magnitude of error was smallest when the bolus injection protocol was employed. CONCLUSION: The data suggest that the 15O-water bolus injection protocol together with the two-parameter fitting procedure provides the most accurate results for MBF and PTF. However, it requires arterial cannulation and a separate carbon monoxide scan. For clinical studies, however, the 15O-water infusion protocol would be a good alternative, providing MBF and PTF results with an acceptable degree of accuracy and without the need for arterial cannulation. PMID- 7799089 TI - Clinical significance of reverse redistribution on 24-hour delayed imaging of exercise thallium-201 myocardial SPECT: comparison with myocardial fluorine-18 FDG-PET imaging and left ventricular wall motion. AB - Clinical significance of reverse redistribution on 24-hr delayed images after exercise 201Tl myocardial SPECT was investigated in 16 patients with recent myocardial infarction. METHODS: Findings of 24-hr delayed 201Tl SPECT imaging were compared with those of glucose-loaded 18F-fluorodeoxyglucose (FDG) imaging by myocardial PET and with left ventricular wall motion obtained by bi-plane contrast left ventriculography. In each patient, transaxial thallium images and corresponding 18F-FDG images were divided into five ROIs. RESULTS: Reverse redistribution was found in 15 of 80 regions. The mean FDG activity score in regions with reverse redistribution was significantly lower than that in regions having normal or slightly decreased thallium activity on 24-hr delayed imaging; it was significantly higher than that in regions having severely decreased or no thallium activity on 24-hr delayed imaging. The mean wall motion score in regions with reverse redistribution was significantly lower than in regions with normal or slightly decreased thallium activity, however, it was significantly higher than that in regions with moderately or more decreased thallium activity. CONCLUSION: These findings demonstrate that in regions showing reverse redistribution on 24-hr delayed 201Tl imaging, myocardial exogenous glucose utilization and left ventricular wall motion had deteriorated, but were not on a level with the scar. PMID- 7799090 TI - Evaluation of an inexpensive screening scintigraphic test of gastric emptying. AB - Our goal was to study the accuracy of a limited assessment relative to the traditional and obtain a more detailed approach to measure gastric emptying. METHODS: We prospectively evaluated 35 patients referred to our laboratory with suspected fast or slow gastric emptying. Transit was measured radioscintigraphically after ingestion of an egg meal containing 99mTc-Amberlite pellets. Gastric emptying was analyzed by power exponential analysis. Diagnostic accuracy of simpler indices (gastric residual at 2 and 4 hr) was determined by comparing the categorization of patients as normal or abnormal relative to previously published normal data from our laboratory. RESULTS: Gastric residual at 2 hr showed greater diagnostic accuracy for accelerated gastric emptying with 90% sensitivity at 90% specificity. Gastric residual at 4 hr was less accurate for accelerated emptying, but was more accurate at detecting delayed gastric emptying with 100% sensitivity at 70% specificity. In contrast, sensitivity and specificity of gastric residual at 2 hr for slow emptying were low (100% sensitivity with 20% specificity) emphasizing the importance of obtaining a scan later than 2 hr for detecting delayed gastric emptying. CONCLUSION: Selective scans taken at 2 and 4 hr provide an excellent screening test for detecting fast or slow gastric emptying; the accuracy of 2-hr data is optimal for accelerated emptying and that of the 4-hr data greater for delayed emptying. This strategy provides a simple, less expensive way to evaluate gastric emptying in clinical practice with acceptable sensitivity and specificity as an initial test for patients with clinically suspected gastric stasis or dumping syndromes. PMID- 7799091 TI - PET-FDG of pleomorphic xanthoastrocytoma. AB - A young patient with pleomorphic xanthoastrocytoma (PXA), a usually benign cerebral tumor, had two recurrences in a short time period. The clinical, pathological and neuroradiological features, including PET with [18F] fluorodeoxyglucose (FDG), are presented. The PET-FDG study revealed the recurrent tumor to be hypermetabolic. The diagnosis was confirmed histopathologically. As the clinical outcome of patients harboring PXA is not easy to predict because of possible recurrence and/or transformation into more aggressive gliomas, we discuss the predictive indicators of more aggressive clinical behavior. PMID- 7799092 TI - A model for critical thinking within the context of curriculum as praxis. AB - The curriculum may be informed by a technical, practical, or emancipatory interest. Curricula informed by these three interests are referred to as curriculum as product, curriculum as practice, and curriculum as praxis (Grundy, 1989) respectively. When curricula are viewed from different perspectives, it is plausible to suggest that each perspective requires a different conceptualization of critical thinking. The literature search revealed that critical thinking has been equated with problem solving, which is congruent with a curriculum-as product orientation. The purpose of this paper is to provide an overview of a conceptual model for critical thinking that is congruent with an orientation to the curriculum as praxis. The model is derived from the work of Freire (1972), Habermas (1972), and Grundy (1989). The key concepts of the model are knowledge, critical reflection, and action. There is a reciprocal relationship between knowledge and action, which is mediated by critical reflection. PMID- 7799093 TI - Critical thinking disposition as a measure of competent clinical judgment: the development of the California Critical Thinking Disposition Inventory. AB - Assessing critical thinking skills and disposition is crucial in nursing education and research. The California Critical Thinking Disposition Inventory (CCTDI) uses the Delphi Report's consensus definition of critical thinking as the theoretical basis to measure critical thinking disposition. Item analysis and factor analysis techniques were used to create seven disposition scales, which grouped the Delphi dispositional descriptions into larger, more unified constructs: open-mindedness, analyticity, cognitive maturity, truth-seeking, systematicity, inquisitiveness, and self-confidence. Cronbach's alpha for the overall instrument, the disposition toward critical thinking, is .92. The 75-item instrument was administered to an additional sample of college students (N = 1019). The alpha levels in the second sample remained relatively stable, ranging from .60 to .78 on the subscales and .90 overall. The instrument has subsequently been used to assess critical thinking disposition in high school through the graduate level but is targeted primarily for the college undergraduates. Administration time is 20 minutes. Correlation with its companion instrument, the California Critical Thinking Skills Test, also based on the Delphi critical thinking construct, was measured at .66 and .67 in two pilot sample groups. PMID- 7799094 TI - A critical thinking model for nursing judgment. AB - Increasingly, the characteristic that distinguishes a professional nurse is cognitive rather than psychomotor ability. Critical thinking is an essential component of nursing. Yet, no clear definition or conceptualization of critical thinking for nursing judgment has existed. Lack of consensus and overlapping definitions may well diminish the profession's ability to articulate this concept and facilitate its development. This article proposes the Critical Thinking Model for Nursing Judgment, which specifies five components: specific knowledge base, experience, competencies, attitudes, and standards. The model has three levels of critical thinking: basic, complex, and commitment. It provides a definition and conceptualization of critical thinking based on a review of the literature and input from nurses and nurse educators. The model provides a first step for development of further research and educational strategies to promote critical thinking as an essential part of autonomous, excellent nursing practice. PMID- 7799095 TI - Study groups: are they effective in preparing students for NCLEX-RN? AB - The effectiveness of faculty-directed study groups as an intervention to prepare nurse candidates for NCLEX-RN was evaluated. The NCLEX-RN performance of a baccalaureate class who had participated in study groups was compared to the performance of a prior class who had not participated in study groups. Academic subgroups within the classes were compared to determine if study groups were equally effective across levels of academic achievement. The possible reasons for the significant difference in the NCLEX-RN passing rate between "at-risk" students who participated in study groups and at-risk students who did not participate in study groups are discussed. Discussion also considers possible factors influencing the generally better performance of study group participants at all academic levels. Suggestions for future intervention research direct attention to time intensity of interventions and research control through random assignments to treatment groups. PMID- 7799096 TI - University-hospital research collaboration provides meaningful experience for student learning. AB - Having the faculty and clinicians work together to formulate a problem for study or to take some portion of an existing study is very useful. Students see that research has practical value and that practice can be affected by systematic investigation of existing nursing practice. Possibly the greatest benefit of students' involvement in this joint project was students' and staffs' realizations that nursing research planned and implemented jointly can benefit both the nurses in practice and the baccalaureate students. Involving students in active participation in joint projects developed and executed in collaboration between clinicians and faculty seems a feasible and worthwhile undertaking. Yet, these projects need to be carefully selected, taking into account the needs of the agency and the students as well as faculty's ability to cope with undergraduate students' inexperience. PMID- 7799097 TI - Effect of type of instructional format on nursing student cue recognition of pulmonary edema: a pilot study. PMID- 7799098 TI - A comparison of baccalaureate nursing programs in the United States and in Taiwan, R.O.C. PMID- 7799099 TI - From advanced practice to academia: developmental tasks and strategies for role socialization. PMID- 7799101 TI - Introduction to an automated hospital information system in baccalaureate education: a pilot project. PMID- 7799100 TI - Coping with declining resources and escalating enrollments: an alternative advisement strategy. PMID- 7799102 TI - Teaching students time management strategies. PMID- 7799103 TI - Age-related challenges in hypertension. Introduction. PMID- 7799104 TI - Alterations in neural cardiovascular control mechanisms with ageing. AB - AGEING AND MECHANISMS OF BLOOD PRESSURE CONTROL: Ageing is associated with functional and structural alterations to the cardiovascular system. Evidence is accumulating, however, that ageing also determines major changes in the effectiveness of mechanisms involved in blood pressure control and that this represents an important determinant of the cardiovascular changes that can be observed in the elderly. DIFFERENCES SEEN IN ELDERLY SUBJECTS: It has been observed that compared to young subjects, in the elderly (1) baroreceptor control of the heart rate and cardiac function is impaired; (2) baroreceptor modulation of the sympathetic drive to the peripheral circulation is impaired, particularly the speed of reflex adjustments to normal and abnormal stimuli; and (3) cardiopulmonary stretch receptors, which tonically inhibit sympathetic tone, the renal release of renin and vasopressin secretion, are impaired. These three factors may account, at least in part, for the raised blood pressure and sympathetic activity in the elderly. They certainly explain the reduced ability of elderly people to maintain blood pressure and blood volume homeostasis, and their increased blood pressure variability over 24 h. ASSOCIATION WITH HYPERTENSION: All these problems are exacerbated if ageing is associated with hypertension, and are highly relevant to antihypertensive treatment. Care should be taken that any antihypertensive drugs selected for treatment in the elderly do not aggravate these basic homeostatic problems. PMID- 7799105 TI - Are calcium antagonists the best option in elderly hypertensives? AB - SUITABILITY OF CALCIUM ANTAGONISTS FOR THE ELDERLY: The efficacy and safety of calcium antagonists have been clearly demonstrated in elderly hypertensive patients. In a double-blind placebo-controlled study in 31 elderly hypertensives treated with nicardipine, we found no consistent electrocardiogram changes, nor in the heart rate, plasma levels of potassium, sodium or creatinine, or uric acid; nor did we find any postural hypotension. The mechanism of action of this class of drugs appears to be particularly appropriate in the treatment of elderly patients, in whom hypertension is characterized by an increase in peripheral resistance and a decrease in arterial compliance. Since vascular tone is ultimately controlled by the intracellular calcium concentration in smooth muscles, agents such as calcium inhibitors, which inhibit calcium influx and induce dilation of small and large arteries, are of particular interest. EXPERIMENTAL EVIDENCE: There is some experimental evidence in hypertensive rats and hypercholesterolaemic rabbits that calcium antagonists can provide some protection against atherosclerotic degeneration. However, the validity of extrapolating these findings to humans is still disputed. POSSIBLE CEREBRAL EFFECT: Calcium antagonists might also have a beneficial cerebral effect. The acute administration of these drugs has been shown to increase cerebral blood flow. Moreover, several studies have shown a protective action against cerebral ischaemia and this may be of particular importance in the very elderly. PMID- 7799106 TI - Why is antihypertensive drug therapy needed in elderly patients with systolodiastolic hypertension? AB - OBJECTIVE: This paper presents a meta-analysis of eight outcome trials of antihypertensive drug treatment in elderly hypertensive patients, and uses the results of these trials to discuss day-to-day issues in the treatment of elderly hypertensive patients. META-ANALYSIS: In an intention-to-treat analysis, cardiovascular mortality was decreased on average by 22% (95% confidence interval -32% to -10%). This decrease was a result of reductions in both coronary and cerebrovascular mortality, by 26% (-40% to -9%) and 33% (-50% to -9%), respectively. So far, the effectiveness of antihypertensive therapy in reducing cardiovascular mortality has not been established with confidence in trials where the diastolic blood pressure at random allocation to treatment groups was below 95 mmHg or in patients above 75 years of age. IMPLICATIONS FOR DAY-TO-DAY PRACTICE: No blood pressure treatment goal has been definitively established but a reduction in systolic blood pressure to about 150 mmHg may be optimal. Extrapolation of trial results to the elderly population with systolodiastolic hypertension at large seems acceptable for a Western population, but may be premature for elderly Asians and Africans. beta-Blockers and especially diuretics are recommended as first-line drugs in elderly patients with symptomless, uncomplicated hypertension, since the effectiveness of other drugs in reducing morbidity and mortality has not yet been established. Recommendations for the treatment of symptomless patients with isolated systolic hypertension may be premature. Ongoing trials on systolic hypertension in Europe (Syst-Eur) and China (Syst-China) may provide further information. PMID- 7799107 TI - Epidemiology of hypertension in the elderly. AB - DISTRIBUTION: Blood pressure tends to rise with increasing age. Six to eight per cent of people aged 60-69 years, and about 12-16% of those aged 70-79 years, are estimated to need treatment for raised systolic and diastolic blood pressures. DETERMINANTS: It seems likely that the rise in blood pressure with increasing age is partly explained by the determinants of blood pressure, such as sodium intake, body weight, physical exercise and alcohol consumption. MORTALITY: There is a linear relationship between the level of diastolic or systolic blood pressure and the risk of stroke or coronary heart disease. However, the relationship between blood pressure and mortality in later life may be obscured if concurrent illness lowers blood pressure; low blood pressure by itself may not be a risk factor for mortality. TREATMENT: Randomly allocated trials have consistently shown that the treatment of hypertension in men and women over 60 years of age reduces the incidence of stroke by about 40%, and some trials have also shown reductions in coronary events. PMID- 7799108 TI - Treatment of elderly hypertensives in Japan: National Intervention Cooperative Study in Elderly Hypertensives. The National Intervention Cooperative Study Group. AB - PREVALENCE OF HYPERTENSION IN ELDERLY JAPANESE PATIENTS: Data collected from post mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53%; one-third of these elderly hypertensives had isolated systolic hypertension. Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications. In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension. INTERIM TRIAL RESULTS: Some interim results have been obtained from a new trial which is currently under way in Japan, the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives, a long-term study comparing the effects of a calcium antagonist (nicardipine) and a thiazide diuretic (trichlormethiazide) on cardiovascular complications in elderly patients with mild to moderate hypertension. PMID- 7799109 TI - Pathophysiology and end-organ damage in elderly hypertensives. AB - PATHOPHYSIOLOGY OF HYPERTENSION: Blood pressure increases with advancing age in most developed countries. The pathophysiology of elderly hypertension is characterized by changes in the structure and function of the cardiovascular system. Changes in arterial structure lead to a decrease in aortic compliance, which augments the aortic pressure component generated by the wave reflection mechanism. The age-related increase in the reflected-wave component of arterial pressure may contribute, at least in part, to the age-related rise in systolic blood pressure. Disproportionately elevated systolic blood pressure in the elderly may account for the progressive increase in left ventricular mass with advancing age. In addition to the changes in vascular and cardiac structures, the haemodynamic function of elderly hypertensives is characterized by increased peripheral resistance as well as reduced cardiac output, renal blood flow and intravascular volume. In contrast to younger hypertensives, the sympathetic and renin-angiotensin systems may not be major factors in the genesis of high peripheral resistance in this patient group. END-ORGAN DAMAGE: The most important end-organ damage in elderly hypertensives is left ventricular hypertrophy with or without coronary heart disease, cerebrovascular disease or renal impairment. Furthermore, this end-organ damage is frequently asymptomatic (silent). The prevalence of silent cerebrovascular disease in particular is surprisingly high in this elderly population. Asymptomatic cerebrovascular disease has been shown to be associated with various cardiovascular risk factors, and depressed neurobehavioural function. Diurnal blood pressure variations appear to be related to end-organ damage. The presence of occult end-organ damage and co-existing diseases common in elderly hypertensives has important clinical implications in the management of this disorder. PMID- 7799110 TI - Type 2 cryoglobulinemia and hepatitis C virus: its recognition and treatment. AB - Type 2 mixed cryoglobulinemia is a relatively common although rarely recognized consequence of chronic hepatitis C virus infection. Its detection should be pursued in individuals with lower extremity vasculitis which occurs in association with other signs of systemic disease such as proteinuria or a peripheral neuropathy. Importantly, HCV-associated cryoglobulinemia can occur in individuals with clinical evidence for cryoglobulinemia but without any evidence of detectable liver injury. Two cases recently seen in Oklahoma demonstrating these points are reported. PMID- 7799111 TI - Introduction to smart card technology and initial medical application. AB - Smart card technology is the name applied to the use of a plastic card with an embedded computer chip. Recent development of smart card software has allowed storage and retrieval of medical information, affording the opportunity to provide a standardized, portable, accessible medical record for use in prehospital and emergency department patient encounters. We describe the smart card concept and its initial deployment in a section of a large Midwestern urban area. PMID- 7799112 TI - Waynoka wisdom. PMID- 7799113 TI - Quo vadis? AB - There is an explosion of DNA and genetic research today. The dignity of life dictates caution be urged in the use of preembryos and fetal parts for these studies. PMID- 7799114 TI - Anesthesiology: where do we go from here? PMID- 7799115 TI - Intramuscular ketamine, midazolam, and glycopyrrolate for pediatric sedation in the emergency department. AB - PURPOSE: The safety and efficacy of a new sedation technique for children with facial injuries in the emergency department were prospectively evaluated. MATERIALS AND METHODS: Thirty-seven children between the ages of 12 months and 7 years old who required sedation for minor surgical procedures were administered an intramuscular injection of ketamine (3 mg/kg), midazolam (0.05 mg/kg), and glycopyrrolate (0.005 mg/kg). A second 1-mg/kg intramuscular injection of ketamine alone was given if needed. Pulse rate, cardiac rhythm, respiratory rate, oxygen saturation, side effects, and behavior were recorded. RESULTS: Satisfactory sedation was achieved after a single injection in 32 children; five others required a second ketamine injection (1 mg/kg). Onset of anesthesia occurred within 6 minutes in 73% of the children who received one injection, and there were generally adequate working conditions for 30 minutes. The average time from initial injection to discharge was 76 minutes. Results of physiologic monitoring, behavioral ratings, and side effects are reported. Emergence delirium and hallucinations were not observed. Ketamine reliably produced dissociative anesthesia without loss of respiratory drive or protective airway tone. Midazolam reduced the incidence of ketamine-induced dysphoric reactions and muscular hypertonicity. CONCLUSION: The use of intramuscular ketamine, midazolam, and glycoyrrolate is a safe, effective, and practical approach to managing selected pediatric injuries in the emergency department. Advanced airway management proficiency is recommended for use of this technique. PMID- 7799116 TI - Use of ibuprofen and methylprednisolone for the prevention of pain and swelling after removal of impacted third molars. AB - PURPOSE: To test a combination treatment of ibuprofen and methylprednisolone for pain and swelling. METHODS: The efficacy of 32 mg methylprednisolone on pain and swelling when given 12 hours before and after surgery in combination with 400 mg ibuprofen three times a day given immediately on the day of the operation and on the two subsequent days following removal of impacted third molars was investigated in a placebo-controlled, intraindividual double-blind study. RESULTS: After use of ibuprofen/methylprednisolone, ultrasonic examination showed a reduction in swelling of 56% (P < .001) compared with the placebo group; measurement with a tape measure showed a 58% (P < .001) reduction in swelling. The visual analog scale showed a reduction of 67.7% in postoperative pain in comparison with placebo. CONCLUSION: The combination of ibuprofen and methylprednisolone has good analgesic and antiinflammatory action. PMID- 7799117 TI - Inhalation sedation with sevoflurane: a comparative study with nitrous oxide. AB - PURPOSE: To evaluate the possibility of using sevoflurane for inhalation sedation. PATIENTS AND METHODS: Thirty-five volunteers were divided randomly into two groups: sevoflurane group (n = 20) and nitrous oxide (N2O) group (n = 15). At the beginning of the sedation they all inhaled 100% O2, then a 0.1 minimum alveolar concentration (MAC) of sevoflurane or 10% N2O with oxygen, a 0.2 MAC of sevoflurane or 20% N2O with oxygen, and 0.3 MAC of sevoflurane or 30% N2O with oxygen for 10 minutes each. RESULTS: The respiratory and cardiovascular functions were stable during inhalation of the gas mixtures. There were five negative comments about breathing N2O, but none about breathing sevoflurane. CONCLUSION: All subjects in the sevoflurane group stated they would be willing to submit to the same inhalation procedure again. PMID- 7799118 TI - Early correction of the nose in unilateral cleft lip patients using an open method: a 10-year review. AB - PURPOSE: To review a 10-year follow-up of cases with rhinoplasty for a cleft lip associated nose deformity done during the preschool years. MATERIALS AND METHODS: Sixteen patients from 16 to 19 years of age were evaluated with two indices: the nasal index and the lobule portion of the columella index. RESULTS: Several years after surgery the results appeared to be reasonably satisfactory. However, as the patients approached their adolescent growth spurt at 15 years of age, undesirable features became obvious. Each patient showed a strikingly bulbous nose. The nasal index of male patients ranged from 68.8% to 82.7% (mean, 75.4%) and that of female patients ranged from 72.7% to 85.0% (mean, 79.2%). The mean value of the nasal index in the Japanese male and female is 58.5% +/- 1.5% and 59.0% +/- 1.0%, respectively. The lobule portion index of male patients ranged from 57.1% to 72.0% (mean, 65.1%) and that of female patients ranged from 62.5% to 82.0% (mean, 74.2%). The lobule portion of the columella constitutes 33% of the total columellar length on average. CONCLUSIONS: A possible cause of the undesirable deformities is use of an open surgical method. A second possible cause is mobilization and suspension of the alar cartilages. These undesirable features may occur only in Oriental noses. PMID- 7799119 TI - Perineural invasion in skin cancer of the head and neck: a review of nine cases. AB - PURPOSE: To review the management and outcome of skin cancer of the head and neck with perineural invasion, a relatively uncommon and complex condition, in nine patients treated between 1965 and 1991. PATIENTS: Seven patients had skin cancers that were larger than 2 cm. All lesions were moderately or poorly differentiated. Curative surgery was performed in all nine cases, with or without radiotherapy. RESULTS: Local recurrence or regional disease appeared in three individuals; surgical salvage produced satisfactory results. At last follow-up (median, 45 months; range, 18 to 201 months), no one had developed intracranial or skull base metastasis; lung cancer was detected in one patient. The crude survival rate was 33% at 5 years and 22% at 10 years. The median survival was 25 months in patients who presented with neurologic symptoms and was 49 months in asymptomatic persons. CONCLUSION: Although the prognosis in patients with skin cancer of the head and neck complicated by perineural invasion is expectedly poor, long-term disease free survival is attainable with the use of aggressive therapy. PMID- 7799120 TI - Type II and type III collagen in mandibular condylar cartilage of patients with temporomandibular joint pathology. AB - PURPOSE: This study was undertaken to examine the presence of type II and type III collagen in the cartilage of the mandibular condyle in different types of temporomandibular joint (TMJ) pathology, including rheumatoid arthritis (RA), to assess to what degree the newly formed tissue is cartilaginous. PATIENTS AND METHODS: Tissue samples from 46 TMJ surgery patients (37 women and 9 men; mean age, 37 years; range, 14 to 76 years) were investigated. The samples were obtained at surgery mostly from anteriorly situated osteophytes or the anterosuperior uneven articular surface of the condyle. Tissue sections were stained with hematoxylin-eosin, toluidine blue, and Gomori's reticular stain. Type II and type III collagens were demonstrated by immunohistochemical staining. RESULTS: The amount of type II collagen was variable in the mandibular condylar cartilage. Type III collagen was found in the new osteoid tissue as well as the new chondroid tissue that was synthesized in the most reactive situations. CONCLUSIONS: Type II collagen synthesis occurred mainly in condylar hypertrophy and the intermediate stage of internal derangement of the TMJ. Type III collagen, which is found in fibrous repair tissue, was also found in sites of repair of mandibular condylar cartilage, including RA and osteomyelitis. PMID- 7799121 TI - Experimental transplantation of hydroxylapatite-bone composite grafts. AB - PURPOSE: This study was undertaken to determine if autogenous bone can be cultivated in vivo in a porous hydroxylapatite (HA) matrix by ingrowth from underlying bone and if this autogenous HA-bone composite graft can then be transplanted. PATIENTS AND METHODS: Five Gottingen minipigs received subperiosteal implantation of one HA block each (40 x 10 x 10 mm), covered by a polylactic membrane, on the ascending ramus of the mandible. After 5 months, half of each implant was harvested and transplanted as an onlay graft to the horizontal ramus of the mandible with simultaneous insertion of a titanium implant. Polychrome fluorescence labeling was done 1, 2, 4, and 8 weeks postoperatively. After 3 months, the vascular system of the animals was filled with BaSO4 for microangiographic examination, and all blocks were retrieved. RESULTS: Fluorescence microscopy showed that there was a significant decrease in deposition of the label in the grafted blocks at 1 week when compared with later labels. After the second week, there were no significant changes. A 20% to 30% decrease in the frequency of fluorochrome staining was noted in the upper third of each block. In this region, microangiography demonstrated highly vascularized tissue and limited bone resorption. CONCLUSION: It was concluded that cultivation of mandibular bone in a porous matrix under guided bone regeneration is possible and that this autogenous HA-bone composite graft can be transplanted at a later date. PMID- 7799123 TI - Prophylactic antibiotics for third molar surgery: a dissenting opinion. PMID- 7799122 TI - Prophylactic antibiotics for third molar surgery: a supportive opinion. PMID- 7799124 TI - Vascular leiomyoma of the mandible: report of a case. PMID- 7799125 TI - Infantile osteomyelitis of the maxilla with concomitant subperiosteal orbital abscess: a case report. PMID- 7799126 TI - Papillary cystadenoma of a minor salivary gland. PMID- 7799127 TI - Recurrent facial metastasis from renal-cell carcinoma: review of the literature and case report. PMID- 7799128 TI - Tetanus: a case report and review. PMID- 7799130 TI - Kallmann syndrome with associated cleft lip and palate: case report and review of the literature. PMID- 7799129 TI - Trismus-pseudocampylodactyly syndrome: report of a case. PMID- 7799131 TI - Autogenous mandibular bone grafts for malar augmentation. PMID- 7799133 TI - A new method of tongue reduction for macroglossia. PMID- 7799132 TI - Dermatography as an adjunctive treatment for cleft lip and palate patients. AB - PURPOSE: To investigate dermatography as a treatment for cleft lip and palate. METHODS: The results of the treatment of 19 cleft lip patients with discoloration of scars and the vermillion border after secondary cleft lip and palate surgery by dermatography and intracicatricial keloidectomy are described. RESULTS: This group of patients has gained self-confidence after treatments, to the extent that their articulation has improved. CONCLUSION: Dermatography can be applied as an adjuvant treatment with good cosmetic and esthetic results. PMID- 7799134 TI - Taking a shot at the editor. PMID- 7799135 TI - Taking a shot at the editor. PMID- 7799136 TI - Taking a shot at the editor. PMID- 7799137 TI - Taking a shot at the editor. PMID- 7799138 TI - In vitro interaction of zinc(II)-phthalocyanine-containing liposomes and plasma lipoproteins. AB - We have studied the interaction of small unilamellar liposomes containing zinc(II)-phthalocyanine (Zn-Pc) with human plasma lipoproteins. High-, low- and very low-density lipoproteins (HDL, LDL and VLDL), were purified from plasma and combined in amounts reflecting their natural abundance in plasma. After short periods of incubation at 37 degrees C, the bulk of Zn-Pc was incorporated into HDL and LDL; very little 14C-labelled palmitoyl oleoyl phosphocholine, the most abundant phospholipid in the formulation, was associated with lipoproteins. When liposomes were incubated in pooled plasma, 73%-85% of Zn-Pc and 27%-34% of radiolabelled phospholipid were recovered with HDL and LDL, indicating a possible role for plasma lipid transfer proteins in the incorporation of phospholipid into lipoproteins. Some Zn-Pc was also found in association with VLDL. The buoyant density of Zn-Pc liposomes increased in a dose-dependent fashion when the particles were incubated with plasma, and it is suggested that this was due, at least in part, to opsonization of liposomes by plasma proteins. PMID- 7799139 TI - Photosensitizer targeting in photodynamic therapy. I. Conjugates of haematoporphyrin with albumin and transferrin. AB - Conjugates of haematoporphyrin (HP) with serum albumin and transferrin were prepared, purified by gel filtration and characterized by high performance liquid chromatography (HPLC), polyacrylamide gel electrophoresis (PAGE) and spectroscopy. Although the fluorescence was somewhat quenched, the conjugates had similar singlet oxygen quantum yields to free porphyrin. The albumin conjugate (HP-BSA) could be divided into monomeric and cross-linked fractions. In NIH 3T3 and HT29 cells, native albumin could not compete with the uptake of HP-BSA and the uptake was greatly enhanced in the absence of serum and in the presence of poly-L-lysine. We infer that the conjugate was mostly associated with the plasma membrane in these cells. The uptake of HP-transferrin showed evidence of a receptor-mediated component in that it was partially inhibited by native protein and increased when transferrin receptors were upregulated by an iron chelator. J774 macrophage-like cells accumulated fluorescence from HP-BSA to a much higher degree than HT29 cells, even though the protein was extensively degraded (HT29 cells did not appear to degrade the protein). The time course of the photocytotoxicity of HP-BSA was prolonged in J774 cells, although their response to free porphyrins was similar to that seen in HT29 cells. Chloroquine inhibited protein degradation without having an effect on the fluorescence uptake. J774 cells acquired more fluorescence and degraded more protein when supplied with cross-linked HP-BSA compared with monomeric fraction. For a given fluorescence uptake, the cross-linked fraction was also more photocytotoxic. We conclude that macrophages can acquire photosensitizer-protein conjugates avidly and that these are delivered to the lysosomes. These types of conjugate may have applications in targeting fluorescent molecules for diagnostic imaging and for the photodynamic treatment of macrophage malignancies. PMID- 7799140 TI - Photoreactivity of biologically active compounds. VII. Interaction of antimalarial drugs with melanin in vitro as part of phototoxicity screening. AB - The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements. PMID- 7799141 TI - Uterotrema Australispinosa n. gen., n. sp. (Digenea: Spirorchidae), a parasite of a freshwater turtle Emydura macquarii from southern Queensland, Australia. AB - Uterotrema australispinosa n. gen., n. sp. from the heart of the Murray River turtle Emydura macquarii (Pleurodira: Chelidae) is distinguished from other members of the Spirorchidae by the presence of a voluminous uterus; a single, lobed testis occupying the posterior quarter of the body; linear rows of 5-6 spines arranged along the lateral margins of the hindbody from the posterior rim of the acetabulum to the posterior end of the body; and the posterior end ventrally curved with a dorsal cluster of spines near the terminal end. This is the first report of a spirorchid from a member of the family Chelidae and from Australia. PMID- 7799142 TI - On Genarchella isabellae (Digenea: Derogenidae) from cichlid and pimelodid fishes in Mexico. AB - Evaluation of comparative material, including type specimens, of 2 derogenid species (Digenea: Derogenidae) in freshwater fishes of the families Cichlidae and Pimelodidae in Mexico revealed the invalidity of Genarchella luistoddi (Jimenez, Guajardo, and Briseno, 1981), a parasite of cichlid fishes in northern Mexico. This taxon is considered to be conspecific with Genarchella isabellae (Lamothe Argumedo, 1977), originally described from the pimelodid Rhamdia guatemalensis (Gunther) and frequently occurring in cichlids of the genus Cichlasoma in southeastern Mexico. PMID- 7799143 TI - Light and electron microscopic examination of so-called piroplasms of fishes from Atlantic Canada and systematic revision of the Haemohormiidae (Incertae sedis). AB - Haemohormidium terranovae infections in American plaice and infections with a similar parasite in oceanpout were examined by light and electron microscopy. All plaice were infected at the time of capture and remained infected for over 2 yr. Prevalence in oceanpout varied seasonally between 0% and 80%. Uninucleate, binucleate, and tetranucleate forms were found in both species. In addition, octonucleate stages were observed in some erythrocytes of infected plaice. The presence of DNA in parasite nuclei was confirmed. There was no evidence of any ultrastructural feature characteristic of the phylum Apicomplexa. It is proposed that the genus Haemohormidium Henry, 1910 be considered incertae sedis and the senior synonym to Haematractidium Henry, 1910. PMID- 7799144 TI - Antitrypanosomal activity of phosphonylmethoxyalkylpurines. AB - Phosphonylmethoxyalkylpurines and -pyrimidines exhibit potent activity against a broad spectrum of DNA viruses. We evaluated some of these nucleotide analogues for antitrypanosomal activity in vitro and in mice. The most active compounds were (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA) and (S)-9-(3 hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine (HPMPDAP), which inhibited growth of Trypanosoma brucei brucei by 50% (EC50 value) when incubated in vitro for 24 hr with 0.23-5.69 micrograms drug/ml. Both compounds completely eliminated multidrug-resistant T. b. brucei in culture at 1 microgram/ml after 4-5 days exposure. Mice infected with drug-susceptible T. b. brucei were cured with 2 doses of 10 mg/kg HPMPDAP. Two or 5 doses of 50 mg/kg 9-(2 phosphonylmethoxyethyl) adenine (PMEA) or 9-(2-phosphonylmethoxyethyl)-2,6 diaminopurine (PMEDAP), respectively, were necessary to eliminate T. b. brucei infections in mice. Mice infected with multidrug-resistant T. b. brucei were not cured with the above dosages. The most active compound against Trypanosoma congolense was PMEDAP with an EC50 value of 3.21-11.63 micrograms/ml. Thus, some of the phosphonylmethoxyalkyl purines showed potential as antitrypanosomal compounds at dosages that are below those toxic for mice. PMID- 7799145 TI - Cultivation of Leishmania braziliensis in an economical serum-free medium containing human urine. AB - Leishmania braziliensis cells are difficult to culture in vitro and usually require media supplemented with serum for sustained cell division. Fresh, sterile urine is an inexpensive substitute for serum in the culture of 2 strains of L. braziliensis, 1 infected with Leishmania RNA virus 1, and 1 uninfected. In the presence of urine, both the infected and the uninfected strains grew to the same final cell density as the same strains grown in the presence of serum. One strain of Leishmania major was also successfully cultured in urine-supplemented media. PMID- 7799147 TI - Further evidence of regular sporulation by Haplosporidium nelsoni in small oysters, Crassostrea virginica. AB - During a field study to determine the susceptibility of the Pacific oyster Crassostrea gigas to Chesapeake Bay oyster pathogens, sporulation of Haplosporidium nelsoni was observed in eastern oysters Crassostrea virginica being used as controls. The C. virginica were obtained from 2 sources on 19 May 1993, a wild population in the upper Rappahannock River, Virginia (59.6 mm mean shell height) and a hatchery-reared population from Chesapeake Mari-culture that was held in the Wye River, Maryland (42.2 mm mean shell height); they were deployed in the York River, lower Chesapeake Bay on 29 June 1993. Both groups of C. virginica became heavily infected with H. nelsoni in early July 1993. Sporulation was observed in both groups on 8 September but was most prevalent in the smaller Maryland oysters where it reached 36% of infected oysters. Oysters of 72.3 mm mean shell height deployed at the same location in May 1993 also became heavily infected with H. nelsoni, but no cases of sporulation were observed in these larger oysters. These results provide further evidence that sporulation of H. nelsoni occurs regularly only in oysters approximately 1 yr old or less. PMID- 7799146 TI - Host specificity of Rhabdochona canadensis (Nematoda: Rhabdochonidae) in Nebraska. AB - Intermediate and definitive host specificity of Rhabdochona canadensis in Nebraska were investigated. Mayfly nymphs Trichorythodes sp. and Caenis sp. were found to serve as experimental intermediate hosts. Development inside the nymphs required approximately 10 days, with the worms passing through 2 molts and then becoming encapsulated in the hemocoel as infective third-stage juveniles. Survey data revealed that only the red shiner Cyprinella lutrensis serves as definitive host for R. canadensis in nature. Laboratory infections of Notropis dorsalis, N. stramineus, and Fundulus zebrinus, all of which were uninfected in nature, were attempted to determine if observed specificity was due to physiological or ecological factors. Two individuals of N. dorsalis became infected with R. canadensis, but no development was observed. Both N. stramineus and F. zebrinus were incapable of becoming infected. Thus, definitive host specificity in this system seems to be mediated by both physiological and host ecological factors. PMID- 7799149 TI - Aeginina longicornis (Amphipoda: Caprellidea), new intermediate host for Echinorhynchus gadi (Acanthocephala: Echinorhynchidae). AB - Cystacanths of the acanthocephalan Echinorhynchus gadi were found infecting the caprellid amphipod Aeginina longicornis on Banquereau, an offshore bank on the Scotian Shelf east of Nova Scotia, Canada. Two of 229 amphipods (0.9%) were each infected with a single male cystacanth. This is the first report of an intermediate host for E. gadi in the western Atlantic Ocean and the first record of A. longicornis as an intermediate host for any helminth. The cystacanths are described. PMID- 7799148 TI - Influence of season and habitat on Ixodes scapularis infestation on white-footed mice in northwestern Illinois. AB - The effects of season and habitat on the infestation of the white-footed mouse (Peromyscus leucopus) by immature Ixodes scapularis were studied at Castle Rock State Park, northwestern Illinois, during June-October 1991. Relative density of larvae on mice was higher in mid-late summer (13.7 ticks per mouse) than during the rest of the study period, whereas prevalence of nymphal infestation was highest in early summer (33.3%). Relative density of I. scapularis larvae and prevalence of nymphs on mice did not differ significantly among bottomland forest, field-forest ecotone, and upland forest habitats. In bottomland forest, total number of ticks collected from mice (472 larvae and 13 nymphs) and P. leucopus population density (6.6 mice per 0.36 ha) were higher than in the other habitats. Temporal patterns of numbers of larvae collected from mice and through dragging in bottomland forest were significantly correlated. PMID- 7799150 TI - New host and geographic records for coccidia (Apicomplexa: Eimeriidae) from North American turtles. AB - Two-hundred-fifty-three turtles, representing 26 species within 5 families (Chelydridae, Emydidae, Kinosternidae, Testudinidae, Trionychidae) were examined for coccidia. Of these, 127 (50%) were found to harbor 1 or more of 28 species of eimerians, or isosporan, or both. One-hundred-thirteen (89%) of the infected turtles were aquatic species, whereas only 14 (11%) of the infected turtles were terrestrial species. Two-fold more aquatic turtles were infected with coccidia (113 of 200, 57%) compared to only 26% (14 of 53) of the terrestrial species. This report documents 14 new host and 8 new geographic records for eimerians from turtles in Arkansas and Texas. PMID- 7799151 TI - Study on the life cycle of a sexually transmitted nematode parasite of a terrestrial snail. AB - A technique for the artificial infection of the snail Helix aspersa by its parasite the nematode Nemhelix bakeri is described. The snail is relaxed by injection of an anesthetic, and 1 gravid female worm is introduced into the genitalia through the genital pore. Half of the injected snails were successfully infected. Following the course of infection over time indicated a 1:1 sex ratio, that the maximum number of progeny produced by injected female worms was 7, and that the development time of female worms was 56 days. The first generation of gravid females was found 100 days after infection. A survey of naturally parasitized snails was also conducted. The sex ratio of worms was in equilibrium, with a mean number of 2.4 larvae per female. The development time (56 days) and the body size (2.47-4.00 mm) of female N. bakeri are similar to those of a related species Cosmocercoides dukae (52-57 days and 1.66-4.34 mm), although the life cycle and biogeographic distribution for each of them are distinct. PMID- 7799152 TI - Second intermediate host-specificity of Haematoloechus complexus and Haematoloechus medioplexus (Digenea: Haematoloechidae). AB - Second intermediate host-specificity was examined for 2 species of the frog lung fluke genus Haematolechus. Nine species of freshwater arthropods were exposed to cercariae of H. complexus and H. medioplexus. Metacercariae of H. complexus developed in all arthropod species used. Metacercariae of H. medioplexus developed only in anisopteran odonate naiads. This difference in host utilization may have epizootiological implications. The potential development of H. complexus in a greater number of arthropods than H. medioplexus may increase the chances of ingestion of H. complexus by an anuran host. The range of arthropods parasitized by H. complexus indicates that host-specificity of the metacercarial stage of this fluke is not restricted by the phylogeny of aquatic arthropods. PMID- 7799153 TI - Presidential address. Toward a national plan for parasite collections. PMID- 7799154 TI - Introduction of Timothy P. Yoshino as the Henry Baldwin Ward medalist for 1994. PMID- 7799155 TI - Acceptance of the 1994 Henry Baldwin Ward Medal. PMID- 7799156 TI - Presentation of the President's Special Award for Distinguished Service. PMID- 7799157 TI - Parasites, immunology of hosts, and host sexual selection. AB - Parasite-mediated sexual selection is reviewed with special emphasis on the bird literature. Choosy females may benefit from choosing parasite-free mates if such males provide better parental care, do not transmit contagious parasites, or provide resistance genes to offspring. There is evidence in support of each of these mechanisms. The immunocompetence handicap hypothesis posits that secondary sexual characters reliably reveal the ability of males to resist parasites due to the immunosuppressive effects of testosterone and other biochemicals. Several aspects of these negative feedback mechanisms are supported by laboratory studies, but evidence from free-living animals is almost completely absent. Corticosterone rather than testosterone may potentially mediate the immunocompetence handicap mechanism. A simple version of the immunocompetence handicap is developed suggesting that body condition of male hosts is a sufficient mediator of the handicap mechanism of reliable sexual signaling. Sexual selection appears to be more intense in sexually dichromatic bird species, and comparative studies using pairwise comparisons of closely related taxa reveal that sexually dichromatic bird species have larger spleens, larger bursa of Fabricius, and higher concentrations of leukocytes than monochromatic species. Parasite-mediated sexual selection is proposed to affect parasite biology by increasing (1) the variance-to-mean ratio in parasite abundance, (2) variance in the intensity of natural selection affecting hosts, and (3) speciation rates among parasites exploiting hosts subject to intense sexual selection as compared to those subject to less intense selection. PMID- 7799158 TI - A chemokinetic response in Schistosoma mansoni cercariae. AB - Schistosoma mansoni cercariae have been shown to aggregate in the presence of glass slides treated with clear nail varnish and linoleic acid. In choice chambers cercariae move toward the stimulant, but this behavior is not seen when linoleic acid is omitted. After 30-45 min, the cercariae were concentrated near the end of the choice-chamber containing the linoleic acid slide. When the cercariae were added in the center of the choice chamber, they formed a diffuse cloud that dispersed slowly in both directions in the absence of linoleic acid. Cercariae aggregating in the vicinity of a stimulant surface are not immediately stimulated to commence penetration; this appears to be time and dose related. PMID- 7799159 TI - Demonstration of a novel UDPGalNAc:GlcNAc beta 1-4 N acetylgalactosaminyltransferase in extracts of Schistosoma mansoni. AB - It was recently demonstrated that complex-type N-linked oligosaccharides in glycoproteins synthesized by Schistosoma mansoni contain the unusual terminal sequence GalNAc beta 1-4GlcNAc beta 1-2Man alpha 1-2R. This structure suggests that the parasite might contain a novel glycosyltransferase that can add GalNAc to terminal GlcNAc residues in N-linked oligosaccharides. This report describes an assay for this enzyme, designated UDPGalNAc:GlcNAc beta 1-4 N acetylgalactosaminyltransferase (beta 1-4GalNAcT), and demonstrates the presence of the enzyme activity in schistosome extracts. As an acceptor for the beta 1 4GalNAcT, we prepared from human fibrinogen a truncated biantennary glycopeptide that contained terminal GlcNAc residues. When this acceptor was incubated with schistosome extracts in the presence of UDP-[3H]GalNAc, Mn2+, and detergent, [3H]GalNAc was transferred to the glycopeptide acceptor. Approximately 75% of the radioactivity in the product isolated by lectin affinity chromatography was recovered as [3H]GalNAc following hydrolysis; likewise, a majority of the isolated product was bound by immobilized Wisteria floribunda agglutinin, a lectin that binds to schistosome-derived oligosaccharides containing terminal beta 1-4-linked GalNAc residues. The activity of the beta 1-4GalNAcT in schistosome extracts was dependent on time, protein, and UDPGalNAc. PMID- 7799160 TI - Infectivity and normal development of third stage Brugia malayi maintained in vitro. AB - Shipment of infective-stage filarial larvae (L3s) usually has been accomplished by transporting living infected vectors or L3s cryopreserved in liquid nitrogen. Our objective was to find culture conditions for transporting L3s that would promote survival of Brugia malayi larvae without altering their capacity to infect susceptible animals. In preliminary studies we observed that Ham's nutrient mixture F-12, with antibiotics and 1% fetal calf serum, could support L3s without apparent development for at least 10 days. In order to evaluate the effect of culture temperatures on infectivity, fresh L3s were divided into groups that were either immediately injected into jirds (infectivity control) or incubated for 24, 48, or 120 hr in tightly sealed tubes maintained horizontally at either 0 C, 20 C, or 37 C, before they were injected into jirds. Necropsies were performed on the jirds 120-130 days after injection to recover and count adult worms. Levels of microfilaremia were also determined. We found that L3s held overnight at 0 C, although apparently viable, were unable to survive in jirds. However, larvae kept at 20 C and 37 C produced patent infections with adult worms in normal locations even after 120 hr of in vitro cultivation. There was no statistical difference in mean worm recovery or size of worms from jirds infected with freshly harvested L3s and jirds injected with larvae that were maintained overnight at 20 C or 37 C. When cultured L3s were shipped from Michigan to Connecticut by overnight air courier, along with infected living mosquitos, the L3s appeared to be 99% viable upon arrival. L3s shipped in F-12 produced patent infections in C.B.-17 scid/scid mice with worm recoveries comparable to those observed in mice injected with L3s freshly obtained from shipped mosquitos. PMID- 7799161 TI - Definition of populations at risk for Plasmodium falciparum infection in three endemic areas of Cameroon. AB - Blood samples were collected from 285 individuals attending hospitals in 1 of 3 different regions of Cameroon. Of these, 89 had Plasmodium falciparum parasitemia. Prevalence in the Douala region was drastically reduced above the age of 19. In the Njinikom and Bamenda regions, on the other hand, an appreciable decline in prevalence was not observed until over the age of 49. Enzyme-linked immunosorbent assay (ELISA) values indicate that in Douala, high antibody titers to P. falciparum were present in all age groups tested. In Njinikom and Bamenda, an age dependence was seen in the response, with sera from individuals above 20 having significantly higher ELISA values compared with those below age 20. Generally, individuals with high antibody titers had low or no parasitemia. Results suggest that future malaria control and treatment measures might target high risk populations such as those defined in this study. PMID- 7799162 TI - Annual cycle of Henneguya doori (Myxosporea) parasitizing yellow perch (Perca flavescens). AB - Henneguya doori Guilford, 1963 (Myxosporea) has an annual development cycle on the gills of adult Perca flavescens. The cycle involves a period of summer invasion, fall development of plasmodia and initiation of sporogenesis, winter completion of sporogenesis, and spring release of spores. An experiment revealed that rising water temperature in spring promotes cyst rupture and loss. The development of cysts is synchronized within individual fish and among members of the host population. As such, the parasite spends 8-9 mo in perch tissues to produce a single annual generation that culminates in a 4-6 wk period of spore dispersal. The parasite does not appear to be pathogenic. The observed cycle of H. doori repeated itself over 4 yr of sampling in Vinegar Lake, Nova Scotia. PMID- 7799163 TI - Endoreplication in the ovary, testis, and intestine of Strongyloides stercoralis. AB - During development of the free-living adults of the human parasitic nematode Stronglyoides stercoralis, cells in certain tissues grow by endoreplication in which rounds of DNA replication occur without cell or nuclear division. The DNA content of individual nuclei was measured by microdensitometry of Feulgen-stained preparations. In females, some ovarian cells have up to 800 times the haploid DNA content (800C). In males, some cells of the testis have up to 100C. Intestinal cells in both sexes have up to 16C, whereas most other somatic cells have 2C. PMID- 7799164 TI - Experimental immunization of ponies with Strongylus vulgaris radiation-attenuated larvae or crude soluble somatic extracts from larval or adult stages. AB - Protection from Strongylus vulgaris infection through immunization with radiation attenuated third-stage larvae (L3) or crude soluble homogenates from larval or adult stages was examined. Yearling ponies raised parasite-free were divided into 3 immunization groups: radiation-attenuated L3; soluble adult somatic extracts; larval somatic extracts with excretory/secretory products (E/S) from in vitro culture; and 1 medium control group. Ponies were immunized twice; attenuated larvae were administered orally and somatic extracts or controls injected intramuscularly with adjuvant. Approximately 6 wk following the second immunization, all ponies were challenged. Necrospy examinations were performed 6 wk following challenge. Irradiated larvae recipients had the fewest postchallenge clinical signs and lesions and were 91% protected from infection determined by larval recoveries from arterial dissections. Soluble antigen recipients and controls had similar larval recoveries and thus equal susceptibility to challenge. Soluble antigen recipients had more severe clinical signs and lesions than controls, suggesting that parenteral immunization exacerbated postchallenge inflammatory responses. Protection by immunization with irradiated larvae was associated with an anamnestic eosinophilia and postimmunization antibody recognition of S. vulgaris L3 surface antigens. Histologic staining of eosinophils within tissues of this group suggested that this immunization induced a cytophilic antibody response that facilitated degranulation. PMID- 7799165 TI - Mechanism of lysis of Trypanosoma brucei gambiense by human serum. AB - Resistance to lysis by human serum (HS) is an important parameter used to distinguish Trypanosoma brucei brucei from both Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Neither the exact nature of the trypanolytic factor (TLF) nor the mechanism of action by which HS lyses susceptible trypanosomes is well understood. This report tries to elucidate the role played by the variable surface glycoprotein (VSG) coat and trypanosome surface-related processes in the mechanism of HS lysis of HS-sensitive (HSS) and HS-resistant (HSR) trypanosomes. Procyclic forms of T. brucei gambiense transformed from either HSS or HSR bloodstream stages were found to be HSR. These procyclic forms were shown to have lost their VSG coat. However, the addition of excess soluble VSG from HSS trypanosomes did not block lysis of HSS trypanosomes. Human serum lysis was significantly inhibited if the trypanosomes were incubated with membrane stabilizers, i.e., including cytochalasins (B, D, and E specifically), zinc acetate, vinblastine, and benzyl alcohol, or with the lysosomotropic agents ammonium chloride and chloroquine. The inhibition exerted by these compounds was always reversible. The results in this report, taken together, strengthen the hypothesis that the lytic factor interacts with and moves along the trypanosome surface to be internalized eventually. PMID- 7799166 TI - Immunization against Taenia crassiceps cysticercosis: identification of the most promising antigens in the induction of protective immunity. AB - Cross immunity between Taenia solium and Taenia crassiceps parasites points to T. crassiceps cysticercosis as a convenient model to test promising antigens aimed at the development of a vaccine against T. solium cysticercosis. Since total antigens from T. crassiceps metacestodes induce significant levels of protection in pigs against T. solium cysticercosis, we initiated this work to identify the most interesting antigens involved in protection. Twelve different antigen fractions isolated from T. crassiceps cysticerci were evaluated with respect to their capacity to induce resistance against a challenge with 10 T. crassiceps cysticerci in male BALB/cAnN mice. Mice were intraperitoneally immunized with 2 doses of each antigen, 5 or 15 micrograms per mouse. The 12 antigen fractions were classified as protecting (200, 123, 74, 66, 56, 40-50, 27 and 8-14 kDa), facilitating (220-205 kDa), or irrelevant (150-160, 93, 108 kDa), according to their effect on the parasite load. The 3 most promising antigen fractions were reevaluated via subcutaneous immunization with Freund's complete adjuvant. A high level of protection was obtained when antigen fractions of 56, 66, and 74 kDa were used together. Interestingly, antigens with similar molecular weights were also detected in early steps of differentiation in T. solium cysticercosis. These observations may be helpful in the development of a synthetic or a recombinant vaccine against cysticercosis. PMID- 7799167 TI - On the occurrence and morphology of Gyrodactylus pterygialis from saithe Pollachius virens in a Norwegian fjord. AB - A total of 308 Pollachius virens from a fjord near Bergen, western Norway, were examined for Gyrodactylus pterygialis over a 14-mo period; G. pterygialis showed the highest prevalence and density in winter/spring (November, January, March, and April pooled) but was absent in some months (August, September, and November). The morphology of the opisthaptoral hard parts of G. pterygialis were studied throughout the survey, and their variation is discussed with respect to host species, host locality, and different temperatures. On the basis of the present and previous descriptions, it is suggested that G. pterygialis is a parasite infecting gadine fishes of the genera Pollachius and Gadus, and that records from Pacific Eleginus and White Sea herring are distinct from G. pterygialis sensu Bychowsky and Poljansky, 1953. PMID- 7799168 TI - Localization of phenol oxidase in female Trichuris suis. AB - A phenol oxidase (E.C. 1.10.3.1) preparation from adult female Trichuris suis was assayed by both polarographic and spectrophotometric techniques. The T. suis enzyme oxidized most diphenols including 4-methylcatechol (4MC) and dihydroxyphenylalanine but did not oxidize tyrosine. The pH and temperature optima were 6.8 and 36 C, respectively. The Km measured using 4MC as a substrate ranged from 0.12 to 0.4 mM. The highest phenol oxidase activity was isolated in fractions from the adult females that were enriched in eggs relative to the activity in somatic tissue from females and all male tissues that were assayed. Phenol oxidase activity was localized on sodium dodecyl sulfate-polyacrylamide gel electrophoresis substrate gels into 2 bands with M(r)'s of 44,000 and 53,000. An antibody to the 44,000 band recognized 2 bands of 40,000 and 45,000 M(r) on western blot analysis of the enzyme preparation. Immunocytochemical localization of anti-phenol oxidase antibody in serial cross sections of adult female worms indicates that the enzyme is found exclusively in the anterior part of the parasite in the proximal part of the uterus that is posterior to the junction with the stichosome. Eggs located in more distal parts of the reproductive system did not react with the antibody. The results indicate that a phenol oxidase is located in the fertilized eggs of adult female T. suis. It is likely that phenol oxidase contributes significantly to the chemical hardening process in the eggs when they pass out into the external environment. Inhibition of phenol oxidase may reduce the survivability of the eggs and thus minimize contamination of livestock facilities. PMID- 7799169 TI - A review of Neoheterocotyle (Monogenea: Monocotylidae). AB - The monocotylid genus Neoheterocotyle Hargis, 1955 is reviewed and the type species N. inpristi Hargis, 1955 is redescribed and illustrated. Neoheterocotyle ruggierii Cheung and Nigrelli, 1983 is synonymized with N. inpristi. Horricauda Tripathi, 1959 is synonymized with Neoheterocotyle, and the species previously assigned to Horricauda are transferred to Neoheterocotyle as N. bychowskyi (Timofeeva, 1981) n. comb., N. forficata (Timofeeva, 1981) n. comb., N. nagibinae (Timofeeva, 1981) n. comb., N. rhinobatidis (Young, 1967) n. comb., N. rhynchobatis (Tripathi, 1959) n. comb., and N. trilobata (Timofeeva, 1981) n. comb. A key to the species of the genus is included. Although most workers attribute Monocotylinae to Gamble, 1896, the correct authority is Taschenberg, 1879. PMID- 7799170 TI - Phylogenetic relationship of Sarcocystis neurona to other members of the family Sarcocystidae based on small subunit ribosomal RNA gene sequence. AB - Sarcocystis neurona is a coccidial parasite that causes a neurologic disease of horses in North and South America. The natural host species are not known and classification is based on ultrastructural analysis. The small subunit ribosomal RNA (SSURNA) gene of S. neurona was amplified using polymerase chain reaction techniques and sequenced by Sanger sequencing reactions. The sequence was compared with partial sequences of S. muris, S. gigantea, S. tenella, S. cruzi, S. arieticanis, S. capracanis, Toxoplasma gondii, Eimeria tenella, and Cryptosporidium parvum. Alignments of available sites for all 10 species and alignments of the entire SSURNA sequence of S. neurona, S. muris, S. cruzi, T. gondii, and C. parvum were performed. Alignments were analyzed using maximum parsimony and maximum likelihood methods to determine relative phylogeny of these organisms. These analyses confirmed placement of S. neurona in the genus Sarcocystis and suggested a close relationship to S. muris, S. gigantea, and T. gondii. Molecular phylogeny suggests that Sarcocystis spp., which utilize the dog (Canis familiaris) as the definitive host, evolved from a common ancestor, whereas those species (including T. gondii) that utilize the cat (Felis domesticus) as the definitive host evolved from another common ancestor. This suggests a possible definitive host for S. neurona. PMID- 7799171 TI - Phylogenetic systematic analysis of the Trichostrongylidae (Nematoda), with an initial assessment of coevolution and biogeography. AB - Phylogenetic analysis of the subfamilies of the Trichostrongylidae based on 22 morphological transformation series produced a single cladogram with a consistency index (CI) = 74.2%. Monophyly for the family was supported by the structure of the female tail and copulatory bursa. Two major clades are recognized: the Cooperiinae clade with the basal Cooperiinae and Libyostrongylinae+Trichostrongylinae, and the Graphidiinae clade with the basal Graphidiinae and Ostertagiinae+Haemonchinae. Dendrograms presented by Durette Desset (1985) (CI = 56.1%) and Lichtenfels (1987), based on the key to the Trichostrongylidae by Gibbons and Khalil (1982) (CI = 59.0%), were found to be relatively inefficient in describing character evolution and in supporting putative relationships among the subfamilies. Based on the current analysis, the intestine appears to have constituted the ancestral habitat for the trichostrongylids with the stomach/abomasum having been independently colonized in each clade. Assessment of host associations suggests extensive colonization but also a high degree of coevolution with Bovidae and Cervidae for Ostertagiinae+Haemonchinae. Biogeography for this assemblage is complex, but this analysis is compatible with a Palearctic or Eurasian origin for Cooperiinae, Haemonchinae, and Ostertagiinae. PMID- 7799172 TI - A new species of Metabenedeniella (Monogenea: Capsalidae) from the dorsal fin of Diagramma pictum (Perciformes: Haemulidae) from the great barrier reef, Australia with a revision of the genus. AB - Metabenedeniella parva n. sp. is described from the marine teleost Diagramma pictum from Heron Island, Queensland, Australia. The type species of the genus, Metabenedeniella hoplognathi, is redescribed and the generic diagnosis emended. Metabenedeniella parva differs from M. hoplognathi in many respects: M. parva is smaller; in M. parva the accessory sclerites and anterior hamuli are of similar length, but the posterior hamuli are smaller, whereas in M. hoplognathi the accessory sclerites are longer than the anterior hamuli and the anterior and posterior hamuli are of similar length; in M. parva the anterior hamuli span the distance between accessory sclerites and posterior hamuli and the anterior hamuli overlap the posterior hamuli considerably, but in M. hoplognathi the anterior hamuli partially overlap the posterior hamuli and do not extend anteriorly to reach the accessory sclerites; a sclerite close to the common genital aperture in M. parva is absent from M. hoplognathi. The 2 species differ also in some of their soft body parts. Specimens reported previously from the gills of Plectorhynchus chaetodonoides off Okinawa, Japan as M. hoplognathi are considered to be M. parva. The discovery of M. parva from only the dorsal fin of D. pictum at Heron Island enhances the notion that some benedeniine monogeneans from the body surfaces of fish exhibit strong site specificity. PMID- 7799173 TI - Sex offending among juveniles: development and response. AB - This article provides the health care provider with information on normal and aberrant sexual activity in children. It examines the characteristics and risk factors associated with juvenile sex offending behaviors and summarizes treatment approaches taken with children who molest. The primary issues in determining when a child's sexual behavior is abusive include the absence of equality and consent and the presence of coercion. Other than the loss of a parental figure and the presence of emotional problems, few demographic or specific psychologic variables distinguish juvenile offenders for their nonoffending peers. Thus offenders typically come to the attention of health care providers indirectly through their victims. PMID- 7799174 TI - Communicating research findings to readers of clinical nursing journals: guidance for prospective authors. AB - The dissemination of research through publication in professional journals is important for the advancement of pediatric nursing practice. Without knowledge of current research, practitioners cannot take actions to apply research to improve the health of the children and families they serve. To ensure that practitioners can make the most appropriate use of quantitative research findings, research publications must adhere to specific scientific standards for the conduct and reporting of research. This article is intended to guide nurse researchers to adhere to these standards and effectively communicate their research findings to nurses in clinical practice. PMID- 7799175 TI - Office management of the young child with cerebral palsy and difficulty in growing. AB - All infants and young children need adequate caloric intake for optimal growth and development. This is true for children with cerebral palsy, who are at increased risk for nutritional problems. When appropriate weight gain is difficult to attain, professionals must carefully evaluate the child's diet, feeding skills, and neurodevelopmental function; assess parenting behaviors; and look for complications of the child's cerebral palsy that could further impede intake and retention of calories. A number of therapeutic recommendations can be given to families to improve potential weight gain. The opportunity to influence the overall growth of young children with cerebral palsy begins when early and timely interventions are provided to the family. PMID- 7799176 TI - The lasting impact of fetal alcohol syndrome and fetal alcohol effect on children and adolescents. AB - The estimate is that thousands of infants are born each year with fetal alcohol syndrome (FAS) or fetal alcohol effect (FAE). The nursing literature has frequently treated FAS/FAE as something that happens only to infants; the effects of FAS/FAE do not end during infancy but persist into childhood, adolescence, and throughout adulthood. It is possible that many children and adolescents who have FAS or FAE are frequently seen by health care professionals for various reasons, but the fact that they have FAS/FAE may not be recognized. As a result, these children and their caretakers may not receive the care and counseling they need. This article describes how FAS/FAE occurs; how it may be recognized; the potentially devastating effects it can have on children, adolescents, and their caretakers; and how FAS/FAE can be prevented. PMID- 7799177 TI - Educating youths and their parents about the prevention of firearm injury. PMID- 7799178 TI - Hemangiomas. PMID- 7799179 TI - "The pediatric nurse practitioner and the physician assistant: how are we different?". PMID- 7799180 TI - Kawasaki disease. PMID- 7799181 TI - A pediatric nurse practitioner call to arms: new solutions needed for nation's growing public health problem. PMID- 7799182 TI - Promoting helmet use in recreational sports. PMID- 7799183 TI - Establishing a PNP faculty practice clinic for Medicaid EPSDT screening. AB - Faculty practice added a new dimension to teaching clinical skills in a Pediatric Advanced Practice Nursing program. It offered the student immediate feedback concerning didactic knowledge and clinical skills and added consistency to learning obtained in the classroom setting. Inclusion of the Medicaid EPSDT program further enhanced student learning by offering a framework of comprehensive services that the student could offer to the patient in providing holistic well-child care. Research opportunities for faculty and students are also prevalent with the large quantity of data available from administration of the EPSDT program. In addition, many children from indigent settings who would not otherwise receive routine well-child care have been given the opportunity because of this program. The use of a faculty practice model that provides the Medicaid EPSDT screening seems to meet the well-child needs of faculty, students, and patients alike and provides an education/service model congruent with the preventative goals of health care reform today. PMID- 7799184 TI - President's message: national primary care workforce--issues and PNPs. PMID- 7799186 TI - President's message: collaboration--my view. PMID- 7799185 TI - Societal child neglect. PMID- 7799187 TI - Domestic violence: children are victims too! PMID- 7799188 TI - The adolescent athlete. Part II: Injury patterns and prevention. AB - Injuries are some of the most universal and blatant downfalls of participation in adolescent sports, and statistics clearly support the need for improved awareness of injury prevention. Teenagers at risk of athletic injury must be identified through increased nurse practitioner knowledge of common adolescent injury (traumatic and overuse), injuries most prevalent in specific sports, training principles, and sports psychology. The role of other support personnel is also investigated. This article is the second of a three-part series addressing the nurse practitioner's role in health maintenance of the adolescent athlete. PMID- 7799189 TI - Comprehensiveness of well child checkups for children receiving Medicaid: a pilot study. AB - Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) is a Medicaid program designed to provide comprehensive well child care for children from low income families. Each EPSDT checkup should include a physical examination; medical history; assessment of development, nutrition, and immunizations; assessment of hearing, vision, and dental status; and anticipatory guidance. This pilot study of the medical records of 76 children receiving EPSDT checkups in six rural counties in North Carolina provided a preliminary assessment of whether EPSDT checkups included the required components. The study showed that health care providers frequently did not provide adequate documentation of the care provided at the checkup, and it raised questions as to whether children received the required components of the EPSDT checkup. PMID- 7799190 TI - Means, motive, and opportunity: case study research as praxis. AB - Pediatric nurse practitioner survival strongly depends on the implementation of nursing research. As active clinicians, pediatric nurse practitioners are always seeking ways to enhance health promotion, which should include research and practice. Case study research as praxis provides a method that enhances both health promotion and scientific knowledge. This article provides an overview and an example of research as praxis to give pediatric nurse practitioners an exciting research methodology alternative. PMID- 7799191 TI - School reentry and the child with a chronic illness: the role of the pediatric nurse practitioner. AB - Being attentive to the educational needs of chronically ill children is a relatively recent development in American education. Advances in medical sciences that have improved survival rates for some conditions and increased public acceptance of people who are different or disabled and legislation that has established education as an entitlement for all children have allowed for the entrance of many chronically ill children into mainstream education. Successful school reentry is essential if the child is to develop normally, in terms of intellect, social skills, and peer relationships. Caregivers must not lose sight of the fact that school provides opportunities for social, emotional, and cognitive development. Thus the pediatric nurse practitioner can promote the benefits gained from schooling in numerous ways and provide the child, family, and school personnel with the support and information needed for a smooth transition back into the school system. PMID- 7799192 TI - Epstein-Barr virus infection in children: implications for the treatment of infectious mononucleosis. PMID- 7799193 TI - Strabismus. PMID- 7799194 TI - What's so important about blue hands? PMID- 7799195 TI - The "Back To Sleep" campaign. PMID- 7799196 TI - Support for new parents. PMID- 7799197 TI - The teen years--not so fun today. PMID- 7799198 TI - The adolescent athlete. Part III: The role of nutrition and hydration. AB - Physically active adolescents have energy requirements far beyond those who are sedentary. Unfortunately, interest in nutrition is rare unless connected to improved performance. The nurse practitioner has the opportunity to instill enthusiasm in the teenager about adequate nutrition and to educate athletes and families on the effects of diet on growth and sports performance. Alternative nutritional practices are investigated, as are potential dangerous starvation and dehydration risks. This article is the third of a three-part series addressing the nurse practitioner's role in health maintenance of the adolescent athlete. PMID- 7799200 TI - Sick child care: a developmental perspective. AB - Sick child care programs provide an alternative when mildly ill children are excluded from their regular child care program. Although infectious disease implications have been addressed, little attention has been directed to the potentially negative consequences of care by unfamiliar providers in unfamiliar settings. Appropriate options for care during illness must be based not only on the physical but the emotional and developmental needs of young children. PMID- 7799199 TI - Levonorgestrel implant use among adolescents. AB - The levonorgestrel implant (Norplant System; Wyeth-Ayerst Laboratories, Philadelphia, Pa.) is a highly effective and desirable form of contraception for the adolescent population today. Not originally marketed toward this group of young women, it has become a very popular form of birth control for this age group. Even though common side effects are frequently experienced with the use of the Norplant System, timely and reassuring counseling from nurse practitioners is very effective in allaying fears and dissatisfaction. At the Pediatric Clinic for Denton County, Texas, nearly one half of all teenagers enrolled in the Teen Pregnancy Program in 1992 chose the Norplant System as their method of birth control, with very successful results. PMID- 7799201 TI - Diagnosis and management of lead-poisoned children: the pediatric nurse practitioner in a specialty program. AB - Lead poisoning, the leading environmental illness in this country, is a challenge to our health care and social systems. Because they provide routine health care in a variety of settings, including care to children from poor inner city families, who are most at risk for plumbism, nurse practitioners should be knowledgeable about this illness and prepared to care for children who have it. This article describes the role of a pediatric nurse practitioner in a specialty program who cares for children with lead poisoning and informs the general practitioner about prevention, education, treatment, coordination of care, and long-term follow-up for these children and their families. PMID- 7799202 TI - Smokeless tobacco. PMID- 7799203 TI - The use of new antiepileptic medications in pediatric patients with epilepsy. PMID- 7799204 TI - Roseola (human herpesvirus 6). PMID- 7799205 TI - Respiratory syncytial virus infections. PMID- 7799206 TI - Lobbying the "other" branch of government. PMID- 7799207 TI - The handgun as a consumer product. PMID- 7799208 TI - The doll clinic: a preschooler's guide to less fearful health care. PMID- 7799209 TI - Collagenase activity and tissue inhibitor of metalloproteinases-1 (TIMP-1) content in human whole saliva from clinically healthy and periodontally diseased subjects. AB - Total TIMP-1 concentration in whole saliva of periodontally diseased subjects, 137 +/- 67 ng/ml (mean +/- SD), was clearly lower (p < 0.001) than that of clinically healthy subjects, 273 +/- 145, and that of edentulous subjects, 332 +/ 121. On the contrary, both active [1.58 +/- 0.35 units/ml (mean +/- SD)] and total (2.08 +/- 0.25) collagenase activities in TIMP-1-free whole saliva of diseased subjects were significantly higher than the activities (0.14 +/- 0.14 and 0.50 +/- 0.27, respectively) in TIMP-1-free whole saliva of healthy subjects. Most of the total collagenase in whole saliva of healthy subjects consisted of procollagenase, while mainly active collagenase was present in whole saliva from patients with periodontal diseases. Significant reciprocal changes of TIMP-1 and collagenase levels, that is, increase in TIMP-1 concentration and decrease in collagenase activity, were observed after the initial therapy of periodontitis patients. PMID- 7799210 TI - Effects of cytokines on gingival fibroblasts in vitro are modulated by the extracellular matrix. AB - Fibroblast function in gingival tissue is thought to be regulated by the local cellular environment--both the extracellular matrix and soluble factors. In an attempt to artificially re-create this situation fibroblasts have been cultured within 3-dimensional collagen gels in an environment more physiologically comparable to connective tissue. Using such a model we investigated the effects of the extracellular matrix on gingival fibroblast growth and synthetic activity and on the cellular responsiveness to 4 soluble factors--epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta 1) and interleukin-1 beta (IL-1 beta). Fibroblasts cultured within collagen gels showed similar growth rates, an increased production of collagen but reduced levels of hyaluronan synthesis in comparison to cells in monolayer culture. Cellular responsiveness to soluble mediators was also modulated by the collagen matrix, with a generalised reduction in response by cells embedded within the matrix. The stimulatory effects of EGF and PDGF on cell growth in monolayer over a 14-day period were only found during the initial stages of culture within gels. Similarly the stimulation of matrix production by cells induced by TGF-beta 1 on plastic was reduced or even negated when cells were cultured in collagen gels. On plastic IL-1 beta significantly stimulated cell growth but had no effect on either collagen or hyaluronan production by fibroblasts. In gel cultures, this cytokine had no effect on cell proliferation, but significantly inhibited both collagen and hyaluronan synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799212 TI - Periodontal treatment needs in 12 and 15 to 19-year-old school children in the Caribbean Island of Antigua, 1990. AB - A national survey was undertaken in 1990 to investigate the periodontal treatment needs in 12 and 15 to 19-year-olds residing in urban and rural areas of Antigua. Using the CPITN procedure, examination of 246 12 year-old children and 456 adolescents (15-19 years) revealed that the CPITN scores of healthy, gingival bleeding, calculus, 4 or 5 mm and > or = 6 mm periodontal pockets were distributed similarly in urban and rural areas. Calculus was the most commonly recorded score, with a prevalence of 46% in 12-year-olds and 56% in 15-19 year olds. 4 or 5 mm pockets were found in 14% of adolescents, affecting on average less than one sextant per subject, but deep pockets were uncommon, 26% of 12-year olds and 14% of adolescents had periodontally healthy mouths. Scaling and oral hygiene instruction were the predominant treatment needs in both age groups, but the requirement for complex periodontal care in adolescents was low -3% only. PMID- 7799211 TI - Cytotoxicity in bacterial cultures: interaction and cell-specificity, possible factors in periodontal disease. AB - Cytotoxicity in culture media of various growing bacterial strains was estimated by Cr-51 release of labelled target-cells. Interaction studies were made by adding each of the different UV-killed bacteria to the medium with viable bacteria. The reference oral bacterial strains were: Actinobacillus actinomycetemcomitans Y4, Porphyromonas gingivalis, Fusobacterium nucleatum and Streptococcus mitis, which were compared with the reference bacteria Staphylococcus aureus 209 and Staphylococcus epidermidis. The target cells were: gingival fibroblasts (GF), periodontal membrane fibroblasts (PMF), pulpal fibroblasts (PF), HeLa-cells (HeLa), and lymphoid neoplasm cells (LN). Synergistic, as well as antagonistic, effects on target cells were observed. The cytotoxicity of A. actinomycetemcomitans in presence of P. gingivalis is neutralized while in presence of S. aureus it was increased. Bacterial interactions with F. nucleatum and P. gingivalis cytotoxicity were observed. The cytotoxicity of F. nucleatum was increased when cultured together with A. actinomycetemcomitans. Each cell type reacted differently to the toxicity of the supernatant of growth medium in which the same bacterial strain had been cultivated, which indicates cell specificity of the toxins. PMID- 7799213 TI - Cyclic-tension force stimulates interleukin-1 beta production by human periodontal ligament cells. PMID- 7799215 TI - Cumulative nature of periodontal attachment loss. PMID- 7799214 TI - Diacylglycerol in peripheral blood neutrophils from patients with localized juvenile periodontitis. AB - Neutrophils from patients with localized juvenile periodontitis (LJP) show several functional abnormalities. Recently, it has become increasingly apparent that the reason for these changes lies in part at the post receptor level of cellular metabolism. In this study we have analyzed intracellular diacylglycerol (DAG), a second messenger and an endogenous activator of protein kinase C, in unstimulated and agonist-stimulated neutrophils, from five LJP patients showing a chemotaxis defect and matched normal individuals. No difference was observed in the basal cellular DAG between the two groups. In neutrophils from LJP patients the DAG levels increased by 67% and 111% from the basal level following stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and unopsonized zymosan particles, respectively, while in control cells the mean increases were 36% and 65%, respectively. Incubation with serum-opsonized zymosan particles produced an identical rise in DAG in both groups. These data indicate that the stimulation of receptors for FMLP and unopsonized zymosan may produce an enhanced accumulation of DAG in neutrophils from LJP patients. In addition to DAG mass analysis, we determined the effect of R59022, a DAG-kinase inhibitor, on zymosan stimulated luminol-amplified chemiluminescence (CL) of neutrophils. In control cells R59022 significantly enhanced unopsonized zymosan induced CL, but it had no effect on cells from LJP patients, suggesting a possible change in the regulation of DAG-kinase in LJP. PMID- 7799216 TI - Occurrence and identity of proteolytic bacteria in adult periodontitis. PMID- 7799217 TI - TNF alpha and IL-1 beta in serum of LJP patients with normal and defective neutrophil chemotaxis. PMID- 7799218 TI - Porphyromonas gingivalis may multiply and advance within stratified human junctional epithelium in vitro. PMID- 7799219 TI - Differential beta-adrenergic regulation and phenotypic modulation of voltage gated calcium currents in rat aortic myocytes. AB - 1. We studied the beta-adrenergic regulation of voltage-gated Ca2+ channel currents using the whole-cell patch-clamp technique (18-22 degrees C) in freshly isolated and in cultured (1-20 days) rat aortic vascular smooth muscle cells (VSMCs). These currents include a transient low-voltage-activated (LVA) current and two L-type-related high-voltage-activated currents (HVA1 and HVA2, respectively). 2. At 10 microM, the beta-adrenergic agonist, isoprenaline, increased the HVA2 current (65 +/- 30%, n = 10) but had no effect on LVA and HVA1 currents. This potentiation was dose dependent in the range 0.01-10 microM, developed with a slow time course and was mimicked by elevating intracellular cyclic AMP using the permeant analogue dibutyryl cyclic AMP (100 microM). 3. In the well-differentiated freshly isolated myocytes, only the HVA1 current was recorded. In cultured cells, a predominant frequency of occurrence of LVA and HVA1 currents was observed in modulated and differentiated myocytes, respectively. The occurrence of the HVA2 current was stable during culture but this current disappeared when the cells were confluent. It was retrieved when the confluent cells were dispersed and subcultured. 4. In conclusion, we present evidence for a differential beta-adrenergic regulation of three types of Ca2+ channel current in adult rat aortic VSMCs. The differential expression of these currents, associated with marked changes in cell phenotypes in vitro, suggests that they serve distinct physiological functions. PMID- 7799220 TI - Na(+)-activated K+ channels localized in the nodal region of myelinated axons of Xenopus. AB - 1. A potassium channel activated by internal Na+ ions (K+Na channel) was identified in peripheral myelinated axons of Xenopus laevis using the cell attached and excised configurations of the patch clamp technique. 2. The single channel conductance for the main open state was 88 pS with [K+]o = 105 mM and pS with [K+]o = 2.5 mM ([K+]i = 105 mM). The channel was selectively permeable to K+ over Na+ ions. A characteristic feature of the K+Na channel was the frequent occurrence of subconductance states. 3. The open probability of the channel was strongly dependent on the concentration of Na+ ions at the inner side of the membrane. The half-maximal activating Na+ concentration and the Hill coefficient were 33 mM and 2.9, respectively. The open probability of the channel showed only weak potential dependence. 4. The K+Na channel was relatively insensitive to external tetraethylammonium (TEA+) in comparison with voltage-dependent axonal K+ channels; the half-maximal inhibitory concentration (IC50) was 21.3 mM (at -90 mV). In contrast, the channel was blocked by low concentrations of external Ba2+ and Cs+ ions, with IC50 values of 0.7 and 1.1 mM, respectively (at -90 mV). The block by Ba2+ and Cs+ was more pronounced at negative than at positive membrane potentials. 5. A comparison of the number of K+Na channels in nodal and paranodal patches from the same axon revealed that the channel density was about 10-fold higher at the node of Ranvier than at the paranode. Moreover, a correlation between the number of K+Na channels and voltage-dependent Na+ channels in the same patches was found, suggesting co-localization of both channel types. 6. As weakly potential-dependent ('leakage') channels, axonal K+Na channels may be involved in setting the resting potential of vertebrate axons. Simulations of Na+ ion diffusion suggest two possible mechanisms of activation of K+Na channels: the local increase of Na+ concentration in a cluster of Na+ channels during a single action potential or the accumulation in the intracellular axonal compartment during a train of action potentials. PMID- 7799221 TI - GABA receptor mediation of median preoptic nucleus-evoked inhibition of supraoptic neurosecretory neurones in rat. AB - 1. This study evaluated the influence of focal electrical and chemical microstimulation in the median preoptic nucleus (MnPO) on the excitability of putative vasopressin and oxytocin neurones recorded in the supraoptic nucleus of urethane- or pentobarbitone-anaesthetized rats. 2. In vasopressin neurones, single 1 Hz stimulation reduced the excitability of 120/139 cells. Trains of repetitive 5-30 Hz stimulation, or microinfusion of glutamate into the MnPO, similarly induced a cessation in spontaneous phasic or continuous firing in 17/18 and 17/20 vasopressin neurones, respectively. In 20/21 cells, locally applied bicuculline (100 microM) attenuated MnPO-evoked depressant responses whereas strychnine (100 microM) and timolol (20 microM) were without effect on 5/5 vasopressin neurones. In three cells, bicuculline applications were associated with marked increases in MnPO-evoked excitations. 3. In oxytocin neurones, single pulse (1 Hz) electrical stimulation in MnPO evoked an increase in the excitability in 51/59 cells. However, in 6/7 oxytocin cells tested, glutamate microinfusions into MnPO induced prolonged suppression in firing. During trains of stimuli (5-30 Hz), 26/44 cells displayed an initial increase in firing associated with the first few impulses but this was then replaced by suppression of activity; another ten cells displayed excitation alone, and eight cells demonstrated only suppression. The depressant responses evoked during trains of MnPO stimulation were blocked by 100 microM bicuculline (6/6 cells tested) whereas strychnine was ineffective (2/2 cells tested). 4. These results suggest that the MnPO provides a mainly depressant influence on supraoptic vasopressin and oxytocin neurones, perhaps through the activation of postsynaptic GABAA receptors. PMID- 7799223 TI - Spatial integration of local transmitter responses in motoneurones of the turtle spinal cord in vitro. AB - 1. Integration of responses to local activation of transmitter receptors in the dendrites of motoneurones was investigated in a slice preparation of the turtle spinal cord. Membrane-active substances were applied from up to three independent iontophoresis electrodes during intracellular recording from the cell body. 2. Responses to glutamate could be evoked from dendrites closer than 20 microns from the tip of the glutamate electrode. The effects of other substances were more widespread. 3. In normal medium the configuration of a glutamate response was affected by time-dependent anomalous rectification. In the presence of muscarine the sum of glutamate responses from two different dendrites recruited a voltage sensitive plateau potential. 4. The response to glutamate from one dendrite could be attenuated by local application of gamma-aminobutyric acid (GABA) without effects on soma conductance or glutamate responses from other dendrites. 5. The response to glutamate from one dendrite could be selectively enhanced by local application of tetraethylammonium (TEA) or N-methyl-D-aspartate (NMDA) without effects on soma conductance or glutamate responses from other dendrites. 6. NMDA could convert a tonic glutamate response from one dendrite into a phasic response without affecting the configuration of glutamate responses from other dendrites. 7. The effects of TEA and NMDA were facilitated by depolarization and reduced by hyperpolarization. 8. We conclude that the cable structure of motoneurones and the distribution of synapses and voltage-sensitive ion channels provide relative autonomy to non-linear synaptic processing and modulation in confined dendritic regions. PMID- 7799222 TI - Lemniscal and non-lemniscal synaptic transmission in rat auditory thalamus. AB - 1. The central auditory pathway linking the inferior colliculus (IC) and the medial geniculate body (MGB) of the thalamus consists of a segregated ventral lemniscal and dorsal non-lemniscal projection whose synaptic transmission mechanisms remain unknown. Extracellular and intracellular recordings combined with axonal tract tracing and cell staining were made from lemniscal and non lemniscal divisions of adult rat MGB maintained acutely in in vitro explants containing parallel tectothalamic projections. 2. Biocytin deposition within the brachium of the IC revealed dense axonal fibres projecting to the MGB. Thin axonal terminals were found throughout the ventral (MGv) and dorsal (MGd) divisions of the MGB. Bushy cells with tufted or bitufted dendritic branches were primarily found in the MGv. In the MGd, cells were mainly seen as stellate neurones having a radiate dendritic arbor. 3. Electrical stimulation of the brachium of IC invariably elicits fast, excitatory synaptic potentials in both MGv and MGd cells. The evoked responses occurred monosynaptically and were exclusively mediated by glutamate acting on both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Non-lemniscal MGd neurones recorded extracellularly exhibited a strong tendency to discharge in bursts in response to brachium stimulation. In contrast, a large proportion of ventral lemniscal cells tended to discharge in single or dual spikes. Intracellularly, MGd cells, but not MGv cells, showed a predominant, slow synaptic potential mediated by NMDA receptors. 4. It is concluded that the central auditory circuitry linking the tectum and the thalamus is connected monosynaptically via glutamatergic synapses. Lemniscal and non lemniscal thalamic neurones possess distinct response properties which cannot be accounted for by a differential transmitter system or polysynaptic delays as postulated previously. PMID- 7799224 TI - Selective phototoxic destruction of rat Merkel cells abolishes responses of slowly adapting type I mechanoreceptor units. AB - 1. The fluorescent dye quinacrine which accumulates in Merkel cells in touch domes was administered to rats and the effects of excitation light irradiation on the mechanical responses of slowly adapting (SA) type I units innervating the touch domes were investigated. 2. Histological examination showed that after 10 min of irradiation degeneration was specifically localized to Merkel cells loaded with quinacrine. Nerve terminals associated with Merkel cells remained intact, even after treatment. 3. In SA type I units, responses to standard stimulation (a 100 ms ramp followed by a 2.9 s plateau of 400 microns constant displacement) decreased significantly after irradiation of the domes with quinacrine-excitation light through a 'B' filter ('B' light). With 5 min irradiation, the response decreased to 52 +/- 7% (n = 10, mean +/- S.E.M.) of the pretreated value, to 17 +/- 4% with a 10 min treatment and practically disappeared within 20 min. 4. In SA type I units with non-loaded Merkel cells, the response increased to 119 +/- 8% (n = 13) with 5 min irradiation and was 99 +/- 9% with the 10 min treatment. At around 15 min after the onset of irradiation there was a gradual decrease and within 60 min the response disappeared. 5. When responses were divided into phasic (0-120 ms after the onset of stimulation) and tonic (120-3000 ms) components, 'tonic' responses were more affected than 'phasic' ones in quinacrine loaded SA type I units. 6. Stimulus-response curves shifted to the right and downwards in SA type I units with quinacrine-loaded Merkel cells after irradiation, but no significant change was seen in SA type I units without quinacrine. 7. Our observations are consistent with the hypothesis that Merkel cells are responsible for mechanoelectric transduction in SA type I units. PMID- 7799225 TI - Blood-borne interleukin-1 alpha is transported across the endothelial blood spinal cord barrier of mice. AB - 1. Previous work has shown that one mechanism by which blood-borne interleukin-1 alpha (IL-1) may be able to affect the central nervous system (CNS) is by direct transport into the brain across the blood-brain barrier (BBB). The BBB of the brain consists of endothelial (between blood and interstitial fluid) and ependymal (between blood and cerebrospinal fluid) barriers. Which of these barriers IL-1 can cross has not previously been investigated. At the spinal cord, which could be the site of action for some of the effects of IL-1 such as analgesia, the BBB consists only of the endothelial barrier. 2. We show here that IL-1 labelled with 125I (I-IL) is transported across the BBB of the spinal cord by a saturable system similar to the one previously described for the brain. High performance liquid chromatography (HPLC) showed that most of the material entering the spinal cord represented intact I-IL. The BBB of the spinal cord was no more leaky to radioactively labelled albumin than the BBB of the brain and was not disrupted by 50 micrograms kg-1 of IL-1. 3. Capillary depletion showed that most of the I-IL entered the parenchymal-interstitial fluid space of the spinal cord with only a modest amount being sequestered by the endothelial cells of its BBB. 4. I-IL entered the cervical, thoracic and lumbar regions of the spinal cord equally well. I-IL entering at the brain and diffusing caudally was estimated only to account for about 1% of the total radioactivity found in the spinal cord after i.v. injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799227 TI - Effect of arterial-portal glucose gradients and phloridzin on bile glucose levels in perfused rat liver. AB - 1. Bivascular perfused rat liver was used to study the effects of hepatic artery portal vein glucose gradients and the effects of phloridzin on bile glucose levels. 2. Bile glucose levels were examined when glucose concentrations in the hepatic artery (HA) and portal vein (PV) inflows were equal. When the concentration of perfusate glucose was 10 mM, bile glucose remained stable at less than 0.075 mM; when perfusate glucose exceeded approximately 16.0 mM, bile glucose increased rapidly; when 1.6 microM phloridzin and 10.0 mM glucose were co infused, phloridzin entered rapidly into bile and settled at a steady-state concentration of 0.45 +/- 0.04 mM, and bile glucose increased to 3.75 +/- 0.14 mM. 3. During perfusion of HA-PV glucose gradients such that HA glucose was higher than that in the sinusoids, bile glucose levels were increased compared with their levels when HA glucose was equivalent to that in the sinusoids. The converse was also demonstrated. 4. The results regarding phloridzin-sensitive glucose transport in the biliary tree of the rat were consistent with those documented in vivo. The finding that bile glucose levels altered in a manner parallel to that of the HA, although the total inflow remained unchanged, strongly indicated that HA glucose level, rather than that of the PV, performs an important role in control of bile glucose levels. PMID- 7799226 TI - Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture. AB - 1. The increasing utility of transgenic mice in molecular studies of the cardiovascular system has motivated us to characterize the ionic currents in neonatal mouse ventricular myocytes. 2. Cell capacitance measurements (30 +/- 1 pF, n = 73) confirmed visual impressions that neonatal mouse ventricular myocytes in primary culture are considerably smaller than freshly isolated adult ventricular myocytes. With the use of electron microscopy, mitochondria and sarcoplasmic reticulum were found in close association with myofibrils, but transverse tubules were not observed. 3. Action potential durations, measured at 50 and 90% repolarization, were 23 +/- 1 and 42 +/- 2 ms respectively (n = 46). Application of 4-aminopyridine (4-AP; 5 mM) prolonged action potential duration at 50% repolarization by 26 +/- 5% (n = 3). The brevity of the action potential is explained by the rapid activation of a transient outward K+ current upon voltage-clamp depolarization to plateau potentials. 4. Potassium currents identified include an inward rectifier, a large 4-AP-sensitive transient outward, a slowly inactivating 4-AP-insensitive outward, a slowly activating delayed rectifier and a small rapidly activating E-4031 (10 microM)-sensitive delayed rectifier K+ current. 5. Sodium currents (-305 +/- 50 pA pF-1, n = 21) were recorded in 40 mM Na+ with Ni2+ (1 mM) to block Ca2+ currents and with K+ replaced by Cs+. The relative insensitivity of the Na+ current to block by tetrodotoxin (IC50 = 2.2 +/- 0.3 microM, n = 4) is distinctive of the cardiac Na+ channel isoform. 6. Nitrendipine-insensitive (10 microM) Ba2+ currents elicited during steps from -90 to -30 mV measured -25 +/- 5 pA pF-1 (n = 7, 30 mM Ba2+). Decay of these currents was complete during 180 ms depolarizations, even with Ba2+ as the charge carrier. These currents were not present when the holding potential was set at -50 mV. These data support the presence of a low threshold, T-type Ca2+ current. 7. The maximal nitrendipine-sensitive L-type Ca2+ current density was -10 +/- 2 pA pF-1 (n = 8) in 2 mM Ca2+ and -38 +/- 5 pA pF-1 (n = 9) in 30 mM Ba2+. Exposure to isoprenaline (1 microM) resulted in an 82% increase (n = 3) in the amplitude of the Ba2+ currents elicited at 0 mV. 8. Neonatal mouse cardiac myocytes in primary culture possess surprisingly large inward currents given the brevity of their action potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799228 TI - Membrane potential dependence of the kinetics of cationic amino acid transport systems in human placenta. AB - 1. Mediated influx of L-lysine into human placental brush-border membrane vesicles occurs through two systems, one of lower affinity but high capacity, the other of very high affinity but low capacity. These transporters have features characteristic of systems y+ (the classical system) and y+L (recently described in the erythrocyte), respectively. 2. In solutions containing sodium the entry of lysine through the high-affinity system (y+L) is inhibited by the neutral amino acids L-leucine, L-methionine and L-glutamine with comparable high affinity. The removal of sodium reduces the affinity but not the maximal extent of this inhibition. Leucine and methionine, but apparently not glutamine, inhibit lysine entry through system y+ with a much lower affinity. 3. The influx of lysine through system y+ changes markedly in response to alterations of membrane potential. In the presence of an inwardly directed negative diffusion potential created by an inwardly directed thiocyanate (SCN-) gradient, the influx of lysine through this route is accelerated; with an inwardly directed positive potassium diffusion potential, lysine influx through this route is reduced. The influx of lysine through system y+L is much less sensitive to such alterations of potential. 4. Analysis of the kinetic constants characterizing system y+ shows that with a change of potential from zero to negative (approximately -60 mV) the maximum velocity (Vmax) is roughly doubled and the half-saturation constant (Km) halved leading to a 4-fold increase in permeability. For system y+L smaller changes are seen and Km does not change; the resulting increase in y+L permeability is 1.5-fold. 5. These findings are discussed with respect both to the mechanism of membrane transport and placental epithelial function. PMID- 7799231 TI - A comparison of noninvasive body temperature monitoring devices in the PACU. AB - Critical measurement of patient body temperature in the PACU is an important parameter in patient management. Failure to achieve minimal acceptable body temperature standards has been associated with physiological derangement, the application of additional therapy, and prolonged PACU stays. Newer methods to monitor temperature have been introduced into the PACU that have been touted to be adequate for detecting clinically significant changes in temperature. This study compares skin core temperature-corrected liquid crystal thermography, axillary electronic, and oral electronic thermistor readings with temperatures obtained by infrared tympanic membrane thermometry in 215 PACU patients. Regression analysis suggests that when compared with tympanic temperature, the oral method is more accurate and has greater precision than either the liquid crystal or axillary methods. That the incidence of hypothermia depends on the method chosen to assess body temperature is a significant nursing implication. PMID- 7799230 TI - Regulation of intracellular pH in smooth muscle cells of the guinea-pig femoral artery. AB - 1. Intracellular pH (pHi) of smooth muscle cells in isolated strips of guinea-pig femoral artery was measured using double-barrelled pH-sensitive microelectrodes. 2. In modified Krebs solution equilibrated with 5% CO2, pHi was 7.26 +/- 0.14 (n = 36; mean +/- S.D. of an observation) and the membrane potential (Em) was -60.5 +/- 5.5 mV. Removal of CO2 from the superfusing solution caused an immediate transient alkalosis before pHi stabilized at much the same value (7.28 +/- 0.14; n = 16) as in the presence of CO2. 3. The rate of recovery of pHi from experimentally induced acidosis was not measurably affected by the presence or nominal absence of CO2-HCO3-. 4. Application of amiloride (100 microM) blocked recovery from acidosis in the nominal absence of CO2-HCO3- and caused a progressive fall in pHi. In the presence of CO2-HCO3-, application of amiloride allowed a slow recovery to pHi 6.7-7.0, but completely prevented full recovery to the normal pHi. 5. Removal of extracellular Na+ (Na+o) caused a dramatic, progressive fall in pHi in both the presence and nominal absence of CO2-HCO3-. 6. The amiloride-insensitive extrusion of acid equivalents observed in the presence of CO2-HCO3- to pHi 6.7-7.0 was inhibited by removal of Na+o but was not affected by preequilibration with DIDS (see Methods). 7. It is concluded that Na(+)-H+ exchange is largely responsible for the effective extrusion of acid equivalents in these arterial cells, at least from relatively small perturbations. A DIDS insensitive, Na(+)- and HCO3(-)-dependent mechanism provides some recovery from acidosis to a relatively low pHi. 8. Comparison with data obtained in exactly the same manner in smooth muscle cells of the guinea-pig ureter indicates that there are significant differences in the regulation of pHi in different smooth muscles. PMID- 7799233 TI - Increasing patient satisfaction: simple ways to increase the effectiveness of interpersonal communication in the OPS/PACU. AB - Because of changes in health care and reimbursement practices, nurses and staff are being required to do more with fewer measures while patients' needs increase. Nurses can make a difference in meeting those needs an in increasing patient satisfaction by using empathy, imagination, and the "human touch." PMID- 7799232 TI - Complications of autotransfusion with salvaged blood. AB - As a means of limiting homologous transfusions, many centers are using autotransfusion devices during the postoperative period. Although their use may limit the risks associated with homologous blood administration, various adverse effects have been reported including sepsis, disseminated intravascular coagulation, and renal insufficiency. The authors present the case of a 9-year old girl who developed acute cardiorespiratory dysfunction after reinfusion of salvaged blood. The use of autotransfusion devices and the probable mechanisms responsible for adverse effects are discussed. PMID- 7799229 TI - Regulation of intracellular pH in the smooth muscle of guinea-pig ureter: Na+ dependence. AB - 1. Mechanisms involved in the regulation of intracellular pH (pHi) in smooth muscle cells of guinea-pig ureter have been investigated using double-barrelled pH-sensitive microelectrodes in isolated strips of tissue. 2. Removal of CO2-HCO3 from the superfusing solution caused a fall in the steady-state pHi except in a few cells which had been excised from the animal for many hours (usually > 24 h). The pHi value was 7.22 +/- 0.09 (n = 89; mean +/- S.D. of an observation) in solution buffered with 5% CO2-21 mM HCO3-, compared with 6.92 +/- 0.24 (n = 67) in the nominal absence of CO2-HCO3-. Recovery from experimentally induced acidosis was faster in the presence, rather than nominal absence, of CO2-HCO3- (mean half-times of 2.7 +/- 0.7 min, n = 41, and 4.6 +/- 1.3 min, n = 12, respectively). These results suggest the presence of both HCO(3-)-dependent and independent mechanisms for the effective extrusion of acid equivalents. 3. Recovery from acidosis was dependent on external Na+ (Na+o) in both the presence and nominal absence of CO2-HCO3-, with an apparent half-maximal activation at approximately 4 and 20 mM Na+o, respectively. Removal of Na+o in the steady state caused a fall in pHi which proceeded at a faster rate in the presence rather than in the nominal absence of CO2-HCO3-. 4. Amiloride (100 microM-1 mM) reversibly inhibited the recovery from acidosis and caused a fall in the steady-state pHi when applied in the nominal absence of CO2-HCO3-, but had no measurable effect on either the recovery from acidosis or steady-state pHi in the presence of CO2-HCO3 . These results suggest that Na(+)-H+ exchange was responsible for extrusion of acid equivalents in the nominal absence of CO2 and HCO3-, but that it played little part under more physiological conditions. 5. Although Na(+)-H+ exchange appeared to be activated below a pHi of about 7.2, it was incapable of maintaining a 'normal' pHi in the nominal absence of CO2-HCO3- in freshly excised cells, where values between 6.06 and 6.89 were recorded. Only in aged preparations, in which the intrinsic intracellular acid loading was substantially reduced (as judged from the rate of acidification on application of amiloride in the nominal absence of CO2-HCO3-) did the steady-state value approximate to that observed in the presence of CO2-HCO3-, at about 7.2. PMID- 7799235 TI - Practical points in the use of ondansetron. AB - It is the purpose of this article to discuss ondansetron hydrochloride (Zofran Glaxo, Research Triangle Park, NJ) and its mechanisms of action, indications for use, dosage and administration, side effects, and nursing implications. PMID- 7799234 TI - Carbon dioxide toxicity related to a laparoscopic procedure. AB - Laparoscopy has become a routine part of many major and minor surgical procedures. During laparoscopic procedures, carbon dioxide (CO2) is insufflated into the peritoneal cavity to allow visualization of the abdominal viscera. Delay in the elimination of CO2 during the intraoperative and postoperative phases of a laparoscopic procedure has recently been identified. This case study discusses a patient with CO2 toxicity related to the insufflation of CO2 during a laparoscopic procedure. Nurses in the PACU must be alert to the signs of CO2 toxicity after a laparoscopic procedure and be able to correctly interpret arterial blood gases. PMID- 7799236 TI - Research preceptors: assisting the postanesthesia nurse to advance from novice to expert researcher. AB - Benner proposed "novice to expert" to describe and explain the development of clinical skill acquisition in nursing students and practicing nurses. Frequently, nursing students' clinical skill acquisition is facilitated by a clinical instructor or preceptor; however, it is uncommon to facilitate research skills by this method. This article describes the novice-to-expert framework, its applications to practice competency development in students and nurses, and research skill expectations. Developing research skill in PACU nurses through the use of research preceptors is proposed. PMID- 7799237 TI - From juggling to balancing. AB - To survive a constantly changing environment, methods for problem solving and managing change must come from a new mind-set. Rather than looking at and fixing individual parts of a process, the focus must be one of looking at an entire process and determining how well the pieces of that process meet the anticipated outcomes. This involves a change from the deductive to the inductive, from juggling issues to balancing issues. PMID- 7799239 TI - Seven habits. PMID- 7799238 TI - Does your documentation defend or discredit? AB - Documenting medical records is often done hurriedly; it is a last responsibility before the patient is discharged, sometimes after the shift has actually ended. What seemed so clear at the time it was written may be barely legible, unbelievably incomplete, and perhaps legally indefensible later. The patient's chart is a permanent legal record that can powerfully defend or easily discredit the nurse when questions arise. A documentation review could be time well spent. PMID- 7799240 TI - Sleep disorders in anxiety and depression. Marrakech, Morocco, December 1993. Workshop proceedings. PMID- 7799241 TI - Sleep and psychiatric disorders. PMID- 7799242 TI - Sleep in panic disorders. AB - Panic disorder is a common anxiety disorder, which has relatively often its onset during adolescence. Besides panic attacks and avoidance behavior the patients often have sleep disturbances. They suffer from insomnia, nocturnal panic attacks, fear of going to bed or falling asleep and drug- or alcohol-related symptoms such as withdrawal phenomena. PMID- 7799243 TI - Anxiety or depression during withdrawal of hypnotic treatments. AB - The prescription of hypnotics, mostly benzodiazepines, continues at a high level, long-, medium- and short-acting compounds all being used. The indication for these hypnotics is the symptom of insomnia which is often secondary to a primary anxiety or depressive disorder. One problem with the use of hypnotics, particularly shorter-acting ones, is rebound insomnia in that discontinuation may be followed by sleep which is worse than pretreatment levels. Anxiety, which may well have been assuaged by the hypnotic treatment, may also rebound but depression, usually not really helped by the hypnotic, does not alter much. A second problem, on discontinuation of long-term treatment, particularly longer acting hypnotics, is a physical withdrawal syndrome characterized by general malaise, and perceptual symptoms as well as marked increases in anxiety and insomnia. In some patients, however, depressive symptoms predominate. These may be an exaggeration of an on-going depressive disorder or it may appear to arise de novo in patients hitherto free of such an illness. The depression can be quite severe and need rigorous treatment in its own right. It is always useful to enquire about hypnotic/anxiolytic withdrawal in patients presenting with a depressive disorder. Depression is also a prognostic indicator of poor outcome (failure to withdraw successfully) in patients taking benzodiazepine hypnotics chronically. PMID- 7799244 TI - Sleep patterns in depression and anxiety: theory and pharmacological effects. AB - Sleep is invariably disrupted in patients who have depression and in patients with anxiety disorders. Depression and anxiety frequently coexist and are associated with disturbances in various neurotransmitters. The authors explore the relationship between sleep and the two disorders as well as the effects of antidepressants and anxiolytics on sleep architecture. The effects on sleep of various neurotransmitter systems implicated in depression and anxiety are outlined. Lastly, various theoretical models are proposed to account for the above mentioned phenomena and further directions for research are suggested. PMID- 7799245 TI - Sleep disorders in the elderly: depression and post-traumatic stress disorder. AB - We report on two studies of sleep in the elderly. (1) One hundred and ninety eight Spanish outpatients aged over 65 who met ICD-10 criteria for either a depressive episode, a recurrent, or a persistent mood disorder were compared with a matched population of depressives aged under 55. Factorial analysis and multiple regression showed that sleep complaints in the older group correlated less with severity of depression and had a less stable response to pharmacological treatment. (2) Post-traumatic stress disorder (PTSD) symptoms and sleep complaints were studied in 817 World War II veterans from Alsace-Lorraine who had been forcibly drafted into the Wehrmacht and subsequently detained as prisoners of war in Russia. The diagnosis of PTSD was associated with more severe wartime stressors and long internment. Eighty percent of respondants still report recurrent distressing dreams of wartime or captivity events after over 45 years. We analyzed sleep complaints in two elderly populations. Part one describes a Spanish study which compared the nosological significance and treatment response of sleep complaints in depressives aged over 65 or under 55. In part two, we study sleep complaints in former Alsatian prisoners of war (POWs) and analyze the influence of previous stressors and the aging process. PMID- 7799246 TI - Cholinergic neurotransmission, REM sleep and depression. AB - It is known from animal experiments that the regulation of REM and Non-REM sleep is governed by cholinergic and serotonergic/adrenergic neurons in the brain stem. Cholinergic neurons in the gigantocellular field of the tegmentum seem to be responsible for the triggering and maintenance of REM sleep. These findings are of special interest for interpreting abnormalities of REM sleep in depression. Psychiatric sleep research in the last two decades has demonstrated that an early onset of REM sleep and heightened REM density frequently occurs in patients suffering from depression. Extrapolating from animal data on REM sleep regulation, the premature onset of REM sleep in depression may be interpreted as the consequence of a central nervous cholinergic overactivity or muscarinic supersensitivity. In our experimental work we have tested assumptions of the so called reciprocal interaction model of NonREM and REM sleep by cholinergic/anticholinergic stimulation strategies of sleep in healthy subjects. Furthermore, the impact of cholinergic stimulation on sleep in depression, healthy control subjects and other psychopathological conditions was investigated. These studies demonstrated that the most pronounced REM sleep response to cholinergic stimulation occurred in depression. PMID- 7799247 TI - Cost of anxiety disorders: impact of comorbidity. AB - The aim of this study was to assess the relative impact of co-mobidity and of symptom severity on the costs of caring for patients with generalized anxiety disorders (GAD). One thousand and forty-two patients with GAD according to DSM III-R were observed by psychiatrists using a cross-sectional methodology. Demographic, clinical, therapeutic as well as health care utilization data were collected at a single point in time. Patients were stratified according to prevalence of co-morbidity. An economic analysis was performed based on a societal perspective. Hospitalizations and losses of productivity were the two major components of costs both in patients with and without co-morbidity. On the other hand costs of pharmaceuticals remain a marginal component of costs associated with GAD in the two groups. Controlling for confounding variables, the prevalence of health care utilisation was found to be significantly higher in patients with co-morbidity for hospitalization, laboratory tests, medications and absenteeism from work. Most of cost components were found to be significantly higher in patients with co-morbidity. The relative risk of health care utilization was higher in patients with co-morbidity, past history of anxiety, high level of anxiety as well as in older patients. Overall our findings suggest that both co-morbidity and symptom severity play a role in cost generation in GAD patients. PMID- 7799248 TI - Insomnia and depression--sleep EEG changes. PMID- 7799249 TI - Insomnia in relation to depression and anxiety: epidemiologic considerations. AB - Epidemiologic studies show that psychopathology is a very powerful risk factor for the occurrence of insomnia. Depression and/or anxiety are quite prevalent among insomniacs, while insomnia is more than twice as prevalent in depressed than in non-depressed individuals. Moreover, recent data support a strong causal link of insomnia to both depression and anxiety. An exact cause-and-effect relationship between insomnia and psychopathology, however, has not as yet been definitively established. This is probably due to methodological differences across studies, related to design characteristics and the ways insomnia as well as various dimensions of psychopathology have been defined and detected. Thus, more refined psychometric techniques and multivariate methods of analysis should be utilized to elucidate the etiologic interface of insomnia and psychopathology. PMID- 7799250 TI - Hypersomnia associated with mood disorders: a new perspective. AB - Thirty-six subjects affected with hypersomnia associated with mood disorders, 31 with a diagnosis of dysthymia, 4 with a diagnosis of bipolar disorder and one with a diagnosis of major recurrent depression underwent standardized polysomnographic procedures including night 1, MSLT and night 2 (uninterrupted). 36.1% of these subjects had a reduced or intermediate mean sleep latency on the MSLT and 13.8% slept over 9 hr at night. In addition 17 of these subjects underwent prolonged polysomnography during day 2. In comparison with eight subjects affected with idiopathic hypersomnia, mean sleep latency on the MSLT was significantly longer and total sleep time during night 2 and during night 2 plus day 2 was significantly lower in subjects affected with hypersomnia associated with mood disorders. It is concluded that a positive diagnosis of hypersomnia associated with a mood disorder requires both behavioral observation and polysomnography. Among these subjects there may be subjects with well-documented hypersomnia and subjects with anergia facilitating or mimicking sleep. PMID- 7799251 TI - Is hypersomnolence a feature of seasonal affective disorder? AB - We examined hypersomnolence as experienced among individuals meeting standardized diagnostic criteria for Seasonal Affective Disorder (SAD). Data were available from 115 individuals attending a mood disorders clinic specializing in treatment of this disorder. Three modes of assessment were employed: retrospective self reports (Seasonal Patterns Assessment Questionnaire), cross-sectional interviews (Standardized Interview Guide for the Hamilton Depression Scale, SAD Version), and prospective sleep diaries. Results indicated that self-reported total hours of sleep varied significantly across the seasons, with longest sleep occurring in winter and shortest sleep in summer. Seasonal sleep changes, as indicated by the SPAQ did not correlate significantly, however, with severity of depressive symptoms as indicated by the Hamilton scale. Multiple regression analyses indicated that only social activity levels (one of seven SPAQ items) was significantly and uniquely related to the severity of depression. When data obtained by the three instruments were compared, self-reported hours of sleep (whether measured by SPAQ or Hamilton interview) were significantly higher than indicated by prospective sleep diaries. We conclude that hypersomnolence may not be a central feature of SAD and that the validity of the SPAQ as an index of this disorder requires further investigation. PMID- 7799253 TI - Sleep disturbances in depression and anxiety: issues in childhood and adolescence. PMID- 7799254 TI - Sleep disorders and anxiety: biochemical antecedents and pharmacological consequences. AB - Evidence is presented that the most widely used and effective drugs used in the treatment of anxiety and insomnia act by indirectly activating GABA-A receptors in limbic regions of the brain. Since the discovery of the benzodiazepines, different classes of benzodiazepine receptor ligands (such as the cyclopyrroliones and imidazopyridines) have been developed which alleviate anxiety and insomnia by activating different sites on the benzodiazepine-GABA receptor complex to those activated by the 'classical' benzodiazepines as exemplified by temazepam and diazepam. There is evidence that natural ligands also exist in the mammalian brain which can modulate the benzodiazepine-GABA receptor complex. This raises the possibility that insomnia and anxiety states may arise as a consequence of a deficit in the availability of endogenous ligands that act as agonists at these sites. PMID- 7799255 TI - Sleep disorders and stress. PMID- 7799252 TI - Sleep disorders in bipolar depression: hypnotics vs sedative antidepressants. AB - Ninety-six patients with bipolar disorder who attended a lithium clinic were reviewed in a retrospective study. Sleep disorders were studied in 85 depressive episodes. Eighty-one percent of the subjects presented with insomnia; the mixed type being the most frequent (49%) followed by early awakening (25%). The evolution of depression in the patients was compared according to the treatment received for insomnia: sedative antidepressants vs other anxiolytic or hypnotic drugs. Fifteen percent of patients shifted to mania, this group more frequently receiving sedative antidepressants (p < 0.05). Moreover, the patients who had received sedative antidepressants as therapy for insomnia (N = 61) showed a tendency to have a shorter asymptomatic interval before the following relapse (13 months vs 19 months; p = 0.06). In view of these results, we consider that the use of sedative antidepressants as a treatment for insomnia during depressive episodes in bipolar patients could be a factor contributing to worse prognoses; in these cases it appears that the use of other hypnotic drugs would be more advisable. PMID- 7799256 TI - Sleep disorders and depression: the 'chicken and egg' situation. AB - The question of whether sleep disorders are part of the clinical picture of depression or of its aetiology remains unanswered. Still, clinical observation in general, polysomnographic studies and the observed antidepressant effect of sleep deprivation, clearly indicate the intimate relationship between sleep disturbances and depression. PMID- 7799257 TI - Insomnia in anxiety: sleep EEG changes. AB - Anxiety is often paired with sleep disturbances and both interact in a quite complex manner. Sleep (and vigilance) problems are often included in the descriptive definition or in the diagnostic criteria for anxiety disorders. Nevertheless, if anxiety may cause sleep disturbances, it is also known that sleep deprivation may produce symptoms which fall within the symptom complex of anxiety. In this paper, some of the methodological issues encountered when studying sleep and anxiety are discussed. Polygraphic recordings of sleep in anxious patients have consistently shown an increased sleep latency and, quite often, also exhibited a reduced sleep time, a reduced total sleep time, less slow wave sleep, a greater arousal index and an increased duration of wakefulness during sleep. From our own study, we also report anomalies of the first night cycle in anxious poor sleepers who are otherwise indistinguishable from normal controls (with regard to the 'classical' sleep parameters). We have also observed the large interindividual variability of numbers of sleep parameters in anxious people. The question of a potential heterogeneity of the studied groups with regard to their clinical presentation as well as their sleep profile has been raised through our research as well. It is apparent that strategies for exploring the source of the potential heterogeneity of anxiety disorders are still needed. PMID- 7799258 TI - Effective psychiatric nurses. PMID- 7799259 TI - Still a long way to go. PMID- 7799260 TI - Potential sequelae of family history of depression. Identifying family members at risk. AB - 1. There is increasing evidence that depressed clients with and without a family history of depression differ on several clinical features, such as learned resourcefulness, depressed cognitions, and coping capabilities. Subjects reporting a family history of depression do not differ from those with no familial depression in demographic characteristics, severity of depression, or adaptive functioning. 2. Depressed inpatients with a history of family depression, however, are significantly less resourceful and less optimistic than their counterparts with no family history of depression. 3. As resourcefulness and optimism are believed to be learned, nursing interventions for teaching specific skills would be particularly useful in preventing depression and promoting mental health for family members who are at risk for clinical depression. PMID- 7799261 TI - Anticholinergic syndrome. Avoiding misdiagnosis. AB - Anticholinergic syndrome can develop in multiple clinical situations. The disturbance of the central nervous system muscarinic transmission by acetylcholine antagonists or lack of acetylcholine can result in this unpredictable behavioral syndrome. Health care professionals should do the following: Be familiar with common drugs or drug combinations that may induce this condition; Be aware of patients who may be at greatest risk; Be able to identify the cluster of signs and symptoms of anticholinergic toxicity; and Implement appropriate nursing treatment interventions for patients with anticholinergic syndrome. Because this condition is constantly changing, it often is misdiagnosed. Much remains to be studied and understood about the neurophysiology of this condition. Central cholinergic transmission is blocked with the use of many anticholinergic drugs in numerous patient settings. Because acetylcholine plays a significant role in modulating the interactions among most other central transmitters, excessive blockage of this neurotransmitter may result in the unpredictable behavioral condition known as anticholinergic syndrome. PMID- 7799262 TI - A health profile of spousal Alzheimer's caregivers. Depression and physical health characteristics. AB - 1. For caregivers of persons with Alzheimer's disease (AD), each day holds unexpected challenges and losses of personal control. Both physical and emotional health are at risk for caregivers of persons with AD. 2. Depression is a problem for caregivers, whether the spouse with AD remains in the home or has been transferred to a nursing home. 3. It is important for clinicians to advise caregivers that depression is a treatable disorder. When a caregiver complains of sleep problems, a red flag for depression should go up. PMID- 7799263 TI - The importance of relationships in fostering hope. AB - 1. A person with mental illness, such as schizophrenia, can be mobilized to maintain hope. 2. A relationship seems to be the catalyst that allows hope to develop exponentially. 3. A belief in the client's abilities can be a powerful motivator for change. PMID- 7799264 TI - The developmentally disabled, psychiatrically impaired client. Proper treatment of dual diagnosis. AB - 1. As many as 30% to 35% of all developmentally disabled persons have a psychiatric impairment. Nurses must be aware that in a developmentally disabled client, psychiatric impairments are frequently exhibited as negative behaviors. 2. Nursing interventions are the same as those used in general mental health settings, but are adapted to the client's needs. If needed, nurses should encourage the full range of psychiatric medications. 3. Care of these patients requires undertaking much investigative work and review of old files, interviewing persons who know the client well, and doing some guess work. PMID- 7799265 TI - Bibliotherapy: a valid treatment modality. Research-based practice. AB - Clients seem already to be reading on their own for help with difficult life situations. As nurses we can further help clients by referring them to appropriate literary resources. PMID- 7799266 TI - Aunt Janet's sick spells. A lay look at schizophrenia. PMID- 7799267 TI - How I learned to play chess. PMID- 7799269 TI - [Radiological contrast media]. PMID- 7799268 TI - The surveyors are coming. PMID- 7799270 TI - [Mammography in the USA]. PMID- 7799271 TI - [Ultrasound-guided cytopuncture of impalpable solid breast lesions]. AB - We performed 64 echo-guided fine needle (21 G) biopsies of solid unpalpable breast lesions in 58 patients. There was a correlation with cytohistological results in 34 cases (53%): 24 cancers (69% of the biopsied carcinomas) and 10 benign lesions (35% of the benign lesions biopsied). There were 4 false negatives, 7 false positives and biopsy did not contribute to diagnosis in 20 cases (31%). Diagnosis was made in all cases on the combined evidence from mammography, echography and cytology. These results emphasize the problems involved in cytodiagnosis: determining the localization of small lesions, nature of the biopsied lesions (role of existing fibrosis and low cell population in the non-diagnostic biopsies), reading the histological slide. PMID- 7799272 TI - [Role of MRI in pre-clinical breast lesions. Preliminary results]. AB - The purpose of this study is to assess the value of MR imaging in nonpalpable breast tumors. Thirty-two women whose mammogram showed opacity, architectural distorsionor microcalcifications, underwent preoperative dynamic MR studies with quantitative evaluation of contrast enhancement. MR showed early contrast enhancement in 10/12 breast cancers (2 false-negative) and in 6/20 benign lesions (false-positive). Quantitative study of contrast enhancement does not allow clear differentiation between these lesions. Further studies are required to confirm these findings and purpose MR imaging for aid in detection of carcinomas. Multifocal sudden enhancements are possible in benign lesions and incite to limit MR to focal mammographic abnormalities. PMID- 7799273 TI - [A technique of MRI signal processing for functional imaging]. AB - Recent works show the possibility of MRI to study brain functionalities. Today, treatment relies essentially on addition and subtraction of images accumulated during rest and activity periods. But this technic is not discriminating and we have developed a software to see and treat images with filtering algorithm and statistical analysis of signal. The first results are given. Perfections are possible and are being realized. PMID- 7799274 TI - [Scanner in a medical emergency test of the nervous system]. AB - Computed tomography is the essential examination in patients with severe manifestations of neurological disorders. We discuss emergency situations involving the central nervous system due to vascular and infections lesions. Trauma and acute complications of brain tumours, usually seen within a neurosurgical context, are not discussed here. PMID- 7799275 TI - [Diagnosis of broncholithiasis. Role of high resolution tomodensitometry]. AB - PURPOSE: to evaluate high resolution computed tomography (HRCT) in the diagnosis of broncholithiasis. PATIENTS AND METHODS: 10 patients with broncholithiasis underwent chest X ray, fiberoptic bronchoscopy (FOB), CT and HRCT. RESULTS: in 9 cases, chest X rays were abnormal but the diagnosis of broncholithiasis can't never be affirmed. In 9 cases, FOB was abnormal: broncholith were identified in only 2 cases; the other diagnosis were tumor like stenosis (n = 3), inflammatory stenosis (n = 3), extrinsic compression (n = 1). On conventional CT scan, broncholithiasis was suspected in 8 patients but because of volume averaging the relationship between calcified lymph nodes and bronchial tree was difficult to determine exactly. Only HRCT sections, sometimes tilted in the axis of the middle lobar bronchus, can affirm the endobronchial or peribronchial location of calcified lymph nodes in all patients. CONCLUSION: conventional CT scan can suggest the presence of broncholithiasis but HRCT sections are need to affirm the diagnosis. PMID- 7799276 TI - [Ultrasonographic diagnosis of appendicitis. Value and limitations]. AB - Appendicitis is a frequently encountered surgical emergency which can be diagnosed by clinical and laboratory criteria. But there are some atypical cases that ultrasound can help to diagnose. From April the 9th 1992 to April the 11th 1993, we have examined by ultrasound 465 patients entered in our hospital for right lower quadrant pain. 190 patients have been diagnosed as appendicitis and operated (true positive = 124 cases, false negative = 54 cases and false positive = 12 cases). 275 patients have been diagnosed as negative and they are not operated (true = 273 cases, false positive = 2 cases). So in our study, the sensitivity is 70%, the specificity is 95% and the accuracy is 85%. Our scientific report has the objective to show the usefulness and the limits of ultrasound in the diagnosis of appendicitis. PMID- 7799277 TI - [Giant Meckel diverticulum type II. Apropos of a case]. AB - Giant Meckel diverticula type II are very rare. However, in contrast with classic Meckel diverticula the small bowel follow through is often abnormal and suggestive of the diagnosis. PMID- 7799278 TI - [Benign atypical cysts of the kidney: MRI aspects]. AB - The aim of this study was to assess the magnetic resonance imaging (MRI) characteristics of 13 benign complex renal cysts using T1 and T2-weighted images and contrast-enhanced images. The results have been compared to CT and ultrasonographic findings in all cases and correlated with histopathologic data in 12 cases. Five groups have been defined according to the MR features. Group 1: homogeneous low signal intensity on T1-weighted images and homogeneous high signal intensity on T2-weighted images mimicking simple cyst (n = 2); group 2: homogeneous high signal intensity on both T1 and T2-weighted images mimicking hemorrhagic cyst (n = 1); group 3: caracterised by high signal intensity on T1 weighted images and fluid-iron level on T2-weighted images (n = 3); group 4: characterised by fluid-iron level on both T1 and T2-weighted images (n = 3); group 5: pseudotumoral feature: heterogeneous signal intensity and/or wall contrast enhancement (n = 3). Among the 13 indeterminate lesions on ultrasonography and CT, MRI was of diagnostic value in 8 cases, whereas the 5 remaining cases remained indeterminate on MR images. Our results suggest that MRI can be useful in the diagnosis of benign complex cyst of the kidney presenting as indeterminate cystic lesion on other modalities. PMID- 7799279 TI - [Beginning and development of radiology in Strasbourg]. PMID- 7799280 TI - [Parathyroid echography in dialysed patients with chronic renal failure]. PMID- 7799281 TI - [Romain Dumazer (1914-1993)]. PMID- 7799282 TI - [Reliable results in MRI imaging of bone tumors]. PMID- 7799283 TI - [Normal and pathological aspects of the glenoid labrum in opaque arthro-scanner]. AB - The morphology of the glenoid labrum was studied by CT arthrography in 88 patients. These were divided in 2 groups. In the first group, the patients underwent CT arthrography for a clinical instability of the shoulder. The second group was the reference group to study the morphology of the glenoid labrum, it included patients with rotator cuff tears or other pathology of the shoulder, without clinical instability. We described the normal labrum which presents important morphologic variations. Its study may be difficult because of the proximity of capsular structures of the shoulder, mainly the gleno-humeral ligaments. The normal variants and the pathologic aspects of the labrum were studied: the clefts, tears and degenerative phenomenous. The cleft aspect was studied comparatively in the instable population and in the reference population. PMID- 7799284 TI - [Early diagnosis by scintigraphy of segmental collapse of the femur head following femur neck fracture]. AB - In order to obtain an early prediction for segmental collapse of the femoral head after femoral neck fracture, we have studied in 53 cases of the femoral neck fracture using 99mTC-MDP scintimetry. According to the radionuclide uptake ratio of the femoral heads, we can estimate the gravity of the avascular necrosis of the femoral head after fracture and recognize the repair process in the necrotic head. Fifty-three cases of fresh fracture were examined by sequential scintigraphy before operation and during follow up examinations after operation. The radionuclide uptake were all increased in 3 to 4 months after operation as comparing with that done before operation. The uptake ratios in 37 cases decreased gradually and approached 1 in 12 months after operation. All of them have an excellent result during follow up examination 36 months after surgery. The uptake ratios in 19 cases were also increased after operation, but still maintained at a high level in 6 to 12 months. They all showed radiographical signs of segmental collapse 18 to 24 months after operation. These results showed that uptake ratio of the radionuclide bone imaging is able to predict the occurrence of segmental collapse of the femoral head after femoral neck fracture. The time of the diagnosis by scintigraphy for segmental collapse of the femoral head is earlier than that by radiography. PMID- 7799285 TI - [Imaging of spinal osteochondroma of neurologic nature. Apropos of 7 cases]. AB - In this work, on 7 cases of spinal neurological, the authors analyse the use of imaging in the diagnosis and pretherapeutic approach, as well as for the post operative follow-up. They insist mostly on the value of tomographic imaging methods, in particular: computed tomography, which allows the study of mineral structures, and determines the site of implant pedicle; magnetic resonance imaging important to precise the connections between tumor and spinal canal contents. They prove that other imaging methods still possess some interest, particularly standard X-ray, useful in estimating the characteristics of exostosis and identifying spinal lesions. PMID- 7799288 TI - [Value and clinical indications of measurements of the bone mass using X-ray dual photon absorptiometry]. PMID- 7799289 TI - [Normal and pathological twin images of the human body]. AB - The author demonstrates examples of symmetrical images in human pathology. He introduces the subject with arguments of the philosophical and cultural areas. He defines asymmetry and dissymmetry. The symmetrical images are linked to different planes (natural, artificial and mixed). With numerous symmetrical pathological images he demonstrates new teleonomical hypotheses: interchangeable, enantiomorphous, turned, rotated images. The concept of symmetry, asymmetry and dissymmetry leads to the concept of symmetrical thinking in clinical imaging. PMID- 7799286 TI - [A rare cause of multiple lacunae of the cranial vault and temporal bone in adults: histiocytosis X]. AB - Histiocytosis X is an uncommon disease. Temporal bone involvement is a frequent head and neck manifestation. Most patients are under fifteen years of age. The authors report a case of a bilateral extensive temporal involvement complicated with vertigo and peripheric facial palsy. CT plays a dominant role in the diagnosis because of the ability to identify bone destruction, soft tissue involvement and intra-cranial histiocytosis more accurately. PMID- 7799287 TI - [Sacral metastasis of unrecognized renal adenocarcinoma, disclosed during an examination for low back pain. Apropos of a case]. PMID- 7799290 TI - [Medical training in radiology in Vietnam]. PMID- 7799291 TI - [Presentation of the ANDEM report. Evaluation of new techniques of endoluminal revascularization of arteries of the lower limbs]. PMID- 7799292 TI - Caries prevention in infants and young children: which etiologic factors should we address? PMID- 7799293 TI - Impact of HIV on VA dental services: report of a survey. AB - OBJECTIVES: This study assessed knowledge, attitudes, and behaviors related to the treatment of HIV-infected patients by Department of Veterans Affairs (VA) dental personnel. METHODS: A questionnaire was mailed to all VA dentists, hygienists, and EFDA assistants and completed anonymously in May 1991. Descriptive results are reported along with comparisons between the findings from this study and a similar VA survey conducted in 1988, as well as several national surveys of non-VA dentists. RESULTS: Nearly all VA respondents reported participation in some type of continuing education on HIV and infection control. They also reported high compliance with recommended infection control procedures. Furthermore, the findings suggest that VA dentists and hygienists have a high willingness to treat HIV-infected patients, far exceeding that expressed by non VA dentists. However, a high level of anxiety related to occupational exposure to HIV seems to exist. Most respondents perceived a higher risk of HIV infection from commonly encountered occurrences in the workplace than actually exists based on current knowledge. CONCLUSIONS: While efforts to further reduce the risk of infection and improve care should continue, future efforts also should be directed toward reducing the anxiety of VA dental personnel in the treatment of infectious patients. PMID- 7799294 TI - Knowledge of and practices related to caries prevention among Koreans. AB - OBJECTIVES: This study assessed the knowledge and opinions of caries prevention and source of oral health information among Koreans. METHODS: A questionnaire consisting of 36 items was used to interview 2,000 Koreans 10 through 69 years of age. Results for only selected questions are reported. A multistage, stratified, random sampling method was used. RESULTS: Sixty-nine percent of the respondents had heard about fluoride. Only 16 percent knew that some community water supplies in Korea are fluoridated. Fifty-five percent of respondents who knew about community water fluoridation learned the information from television, whereas 28 percent read about it in a newspaper. Among those respondents who reported hearing about community water fluoridation, only 30 percent had precise information about its purpose. Fifty-five percent of the respondents reported that toothbrushing is the best way to maintain good oral health. Almost all respondents (97 percent) reported brushing their teeth one or more times a day. CONCLUSIONS: These data indicate that there is a relatively low level of accurate knowledge about dental caries prevention among Koreans 10 through 69 years of age. The majority of respondents report learning information about oral health from the mass media. PMID- 7799297 TI - Setting the agenda for international collaboration in oral health. PMID- 7799295 TI - Understanding dental service use by older adults: sociobehavioral factors vs need. AB - OBJECTIVES: This study investigated correlates of dental care use in a representative sample of adults aged 70 and older throughout New England. METHODS: Data were collected in in-home interviews and dental examinations. Following Andersen's behavioral model of health services utilization, varied measures of sociodemographic characteristics, dental health attitudes and practices, perceived need for care, and need objectively determined by clinical examination were included as potential correlates. RESULTS: Recency of last visit was associated with positive attitudes toward dental care, regular dental hygiene, and having a usual source of care. Among dentulous subjects, recency of last visit also was related to sex and living arrangements. Frequency of visits for dentulous subjects was associated with the same variables, as well as with age and social class or education, in addition to need for care. For edentulous subjects, only a usual source of care and higher social class were associated with more frequent visits. CONCLUSIONS: Perceived need and attitudes toward dental care are important influences on use of care. Older persons must be convinced of the importance of regular dental care. PMID- 7799296 TI - A comparison of dental caries experience in Native American and Caucasian children in Oklahoma. AB - OBJECTIVES: In 1989 the Oklahoma Area Indian Health Service conducted an oral health survey of children attending public schools in Oklahoma to determine the extent of caries experience in the Native American population. Results were to be used to establish program priorities, gather baseline data, and compare the oral health status of Native American children with their non-Indian peers. METHODS: A total of 934 elementary schoolchildren 5-6 years of age were examined along with 733 high school students 15-17 years of age. The study was designed so that approximately 50 percent of the students examined were Native American. RESULTS: The mean dmfs for the 5-6-year-olds was 5.06 for the Caucasian children and 10.35 for the Native American children, a statistically significant difference (P < .001). For the 15-17-year-olds the mean DMFS for the Caucasian students (5.99) was significantly lower (P < .001) than the mean DMFS for the Native American students (10.12). CONCLUSIONS: The prevalence and severity of caries in these Native American students appear to be substantially higher than in their non Indian peers residing in the same communities. Further study is needed to identify factors contributing to these demonstrated differences in caries experience. PMID- 7799298 TI - Oral health for a healthy life. PMID- 7799299 TI - Building the capacity for the response of the dental profession to the global HIV pandemic: a case study in international collaboration. PMID- 7799300 TI - Developing vs importing oral health resources: the PHS experience in the Pacific. PMID- 7799301 TI - Public health testimony for the Institute of Medicine's Committee on the future of dental education. PMID- 7799302 TI - Roles of melatonin and prolactin in testicular crudescence in mink (Mustela vison). AB - Peripubertal male mink (Mustela vison) were treated with prolactin, melatonin or antibodies against melatonin to determine the effects of altered circulating concentrations of prolactin and melatonin throughout one season of testicular development. Treatment began on 1 October and continued until 4 March. Administration of 0.5 mg ovine prolactin day-1 by minipump increased the circulating concentration of prolactin for the duration of the study and increased serum concentrations of LH. This treatment had no effect on the testosterone concentration or on testis size. Neither chronic treatment with melatonin throughout the period of crudescence nor passive immunization against melatonin for 79 days affected the circulating concentrations of prolactin, LH, testosterone or testis size. These results show clearly that, unlike in other seasonally breeding species, prolactin does not play a significant role in testis growth in the mink. Administration of melatonin to male mink in October did not affect testis growth, presumably because the melatonin signal that cues photoperiodic events had already been received. Administration of antibodies against melatonin did not affect any of the features measured, suggesting that melatonin may have neural but not peripheral effects. Further support for this view can be found in the absence of an influence of melatonin on testis growth or on the plasma concentration of testosterone. PMID- 7799304 TI - Association between the duration of dominance of the ovulatory follicle and pregnancy rate in beef heifers. AB - After luteolysis, subluteal concentrations of progesterone or treatment with a synthetic progestagen result in an extended period of dominance (persistence) of the dominant follicle in cattle. Two experiments studied (1) the relationship between the duration of dominance of the ovulatory follicle and pregnancy rate and (2) the ability of a persistent dominant follicle to ovulate and form a normal functioning corpus luteum. In Expt 1, beef heifers were either untreated (n = 30) or given a synthetic progestagen implant (3 mg norgestomet) for 12 days starting on day 16 of their cycle (n = 32). The mean duration of dominance of the ovulatory follicle differed (P < 0.05) between treated and control heifers (10.8 +/- 1.2 and 3.3 +/- 0.8 days, respectively) and 20 of 26 control and 7 of 30 treated heifers were diagnosed pregnant 28 days after artificial insemination (P < 0.01). In Expt 2, on the first day of dominance of the second dominant follicle, heifers received either a PGF2 alpha analogue alone (controls; n = 18), or prostaglandin and a norgestomet implant for 6 (T6; n = 19) or 10 days (T10; n = 20). Increases in the duration of dominance of the second dominant follicle (controls, 4.1 +/- 0.2 days; T6, 8.6 +/- 0.2 days; T10, 12.1 +/- 0.2 days; P < 0.05) resulted in a decrease in pregnancy rate (controls, 14 of 16; T6, 11 of 19; T10, 0 of 13; P < or = 0.05). Progesterone concentrations on days 7 and 12 and the area of luteal tissue on day 12 after artificial insemination were not different (P > 0.05) between treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799303 TI - A possible role for Ca(2+)-ATPase in human sperm capacitation. AB - Mammalian spermatozoa require extracellular Ca2+, some of which must be internalized, to undergo capacitation and acrosomal exocytosis. The mechanisms controlling the intracellular Ca2+ concentration are unclear, but current evidence suggests that a Ca(2+)-ATPase may be involved. Using treatments that potentially modulate enzyme activity, we investigated this possibility in human spermatozoa; the capacitation state and acrosomal integrity were monitored by chlortetracycline fluorescence. Incubation of cells in the presence of quercetin, a Ca(2+)-ATPase inhibitor, significantly accelerated the transition from the uncapacitated F pattern of chlortetracycline fluorescence to the capacitated, acrosome-intact B pattern within 1 h. This was followed by an increase in the number of cells displaying the capacitated, acrosome-reacted AR pattern. Since most Ca(2+)-ATPases in somatic cells are sensitive to calmodulin, we also investigated the effect of the calmodulin antagonist W-7 on chlortetracycline patterns. At 1-125 mumol l-1, W-7 significantly stimulated capacitation and acrosomal exocytosis. Furthermore, W-7 at 1 mumol l-1 proved to be more effective than W-5, a less potent antagonist, suggesting that the observed responses in human spermatozoa did reflect a calmodulin-sensitive mechanism. When the glucose concentration in the culture medium was varied (from 0 to 5.56 mmol l-1) to alter the availability of ATP for enzyme activity, it was found that a reduced concentration of glucose promoted capacitation more rapidly than did the standard concentration of 5.56 mmol glucose l-1. However, maximal changes, particularly in promoting the shift from the B to the AR pattern of chlortetracycline fluorescence, required millimolar concentrations of glucose during the last few minutes before assessment. Finally, the addition of partially purified mouse sperm decapacitation factor (proposed to activate a Ca(2+)-ATPase and thus maintain a low intracellular Ca2+ concentration) to capacitated human sperm suspensions caused a significant reversal in the capacitation state of cells (from the B to the F pattern). The F pattern of chlortetracycline fluorescence predominates in conditions favouring low concentrations of intracellular Ca2+. From these results, we suggest that a Ca(2+)-ATPase may play an important role during human sperm capacitation. A time-dependent decrease in endogenous enzyme activity would allow the intracellular concentration of Ca2+ to rise to a critical value necessary for initiation acrosomal exocytosis and subsequent successful fertilization. PMID- 7799305 TI - Effects of anoestrus and bromocryptine treatment on the expression of prolactin and LH receptors in the rabbit ovary during lactation. AB - The aim of the present study was to correlate the number of prolactin and LH receptors in the ovary with the changes in sexual behaviour that occur within a few days following parturition in rabbits. Multiparous New Zealand white rabbits at days 0, 3 and 10 of lactation were tested for their receptivity upon presentation to a male. Rabbits were classed as either receptive or nonreceptive at each stage of lactation; half of the animals in each class were treated with bromocryptine to examine the effects of prolactin deprivation. Ovarian receptors for LH and prolactin, as well as the concentration of their corresponding mRNA, were measured at each stage of lactation in every group. Results indicate that receptive behaviour is correlated with significantly more follicles on the rabbit ovary (diameter > 1 mm; P < 0.05) and an increase in the concentration of LH receptor mRNA (P < 0.001) and prolactin receptors (P < 0.05). In addition, on day 4 of lactation, there were significantly fewer follicles in nonreceptive rabbits (P < 0.05). LH receptor content remained constant on days 1 and 4 of lactation but increased on day 11 (P < 0.05). Bromocryptine treatment had no effect on the number of follicles or on the amount of LH receptor mRNA in does, but it significantly increased LH receptors (P < 0.01), and the concentration of prolactin receptor mRNA (P < 0.001), particularly on day 11 of lactation (P < 0.05), and prolactin receptor content (P < 0.001). Receptive rabbit ovaries therefore display more follicles that can respond to an LH surge via newly transcribed LH receptors than do nonreceptive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799306 TI - Increased LH receptor mRNA and extended corpus luteum function induced by prolactin and indomethacin treatment in vivo in hysterectomized pseudopregnant rats. AB - To assess the effects of prostaglandins and prolactin on corpus luteum function and regression, sterile-mated adult pseudopregnant rats hysterectomized on day 5 after mating were injected with indomethacin or prolactin. Daily samples of blood were collected via the tail, from day 12 to day 21, and assayed for serum concentrations of progesterone, 20 alpha-dihydroprogesterone and LH, whereafter corpora lutea and the remainder of ovaries were separated and the tissue content of PGF2 alpha, PGE2 and LH receptor mRNA were measured. Injections of prolactin (8 iu) s.c. or a low dose of indomethacin (200 micrograms kg-1) s.c. were administered twice a day, beginning on day 13 after mating. Both indomethacin and prolactin significantly increased serum progesterone concentrations (P < 0.05; n = 8), and extended the period of functional corpora lutea when compared with controls. Indomethacin, but not prolactin, lowered the concentration of serum 20 alpha-dihydroprogesterone. In the corpora lutea of indomethacin-treated animals, collected on day 21, both prostaglandins measured were reduced in concentration by 50% or more, compared with controls (P < 0.05; n = 8), whereas prolactin had no effect. Both prolactin and indomethacin treatment caused a substantial (tenfold) increase in the concentration of LH receptor mRNA, confined solely to the luteal compartment. These findings in vivo provide further evidence for a luteolytic role of locally synthesized prostaglandins in the rat ovary. Furthermore, prolactin can sustain corpus luteum function by exerting a luteotrophic effect during the late luteal phase, as judged by the stimulation of progesterone synthesis and the expression of LH receptors. PMID- 7799307 TI - Immunohistochemical localization of epidermal growth factor receptors, epidermal growth-factor-like and transforming-growth-factor-alpha-like peptides in chicken ovarian follicles. AB - The purpose of this study was to determine the presence of epidermal growth factor receptor and its potential ligands epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in the tissues of the maturing follicles in the ovary of laying ISA-Brown hens using peptide-specific immunohistochemical methods. Cryostat sections, 6-8 microns thick, were made from fresh-frozen tissues of F1-F4 (largest to fourth largest) and large white follicles and they were immunostained for epidermal growth factor receptor, epidermal growth factor or transforming growth factor alpha using specific polyclonal antibodies. The EGF receptor and both ligands were detected in the granulosa, theca interna and theca externa layers of the follicles. The EGF receptor was localized both in the plasma membrane and cytoplasm of all cell types. EGF was predominantly cytosolic, whereas TGF-alpha was found in the plasma membranes and perinuclear areas of all cell types. The concentration of the receptor and both ligands decreased with follicular maturation. This observation is consistent with our previous observation that the response to EGF and TGF alpha decreases as follicles mature, and thus provides further evidence that the receptor or the ligands may have a regulatory role in avian ovarian function. PMID- 7799308 TI - Modulation of production of matrix metalloproteinases from ovine endometrial cells by ovine trophoblast interferon. AB - Ovine trophoblast interferon modulates the secretion of a number of proteins by ovine endometrium, but only one of these proteins has so far been identified. We examined the effects of trophoblast interferon on the secretion of matrix metalloproteinase-1, -2 and -3 by cultured ovine endometrial cells and determined whether they are mediated via effects on prostaglandin synthesis. Both ovine trophoblast interferon (30 ng ml-1) and human recombinant interferon alpha (50 U ml-1) inhibited the production of latent matrix metalloproteinase-1 and -3 (P < 0.05), as measured by enzyme assays, but had no effect on the secretion of latent matrix metalloproteinase-2. These inhibitory effects were not overcome by PGE2 or PGF2 alpha (each 10 mumol l-1) either alone or in combination. Indomethacin (12 mumol l-1) similarly inhibited the production of latent matrix metalloproteinase 1 and -3, but production was partially restored by adding the prostaglandins either singly or in combination. PGE2 and PGF2 alpha together had no effect on enzyme production. These data were confirmed by gelatin and casein zymography. Northern analysis showed a 4.5-fold increase in the abundance of specific mRNA for latent matrix metalloproteinase-1 following treatment of cells with phorbol myristate acetate, but a marked decrease following interferon treatment. Thus, ovine trophoblast interferon inhibits the production of the latent forms of matrix metalloproteinase-1 and -3 by ovine endometrial cells, and this is independent of its effect on prostaglandin production. PMID- 7799310 TI - Uptake of a mixture of amino acids by mouse blastocysts. AB - Preimplantation mouse embryos exhibit growth at the blastocyst stage when there is a dramatic increase in protein content between days 4 and 5 after hCG treatment. This increse in protein synthesis requires the uptake of amino acids from the surrounding medium, but the consumption of individual amino acids present as a mixture has not been examined. We therefore measured the simultaneous depletion of 18 amino acids by mouse blastocysts in culture on days 4 and 5 after hCG treatment. Two culture media were used: one with amino acids present at concentrations largely based on those reported to give optimal rates of embryo development (M16/mix AA), and a second with the amino acids each at 0.1 mmol l-1 (M16/0.1 AA). After derivatization with o-phthaldialdehyde to yield highly fluorescent products, amino acid concentrations in the media were measured by HPLC. On day 4, seven amino acids were depleted from M16/mix AA at rates significantly greater than zero: aspartate, arginine, glycine, alanine, isoleucine, leucine and lysine; on day 5, nine amino acids were depleted at significant rates: aspartate, glutamate, asparagine, tyrosine, methionine, valine, phenylalanine, isoleucine and leucine. Average amino acid depletion from M16/mix AA was 32% greater on day 5 than on day 4. Aspartate, glutamate, arginine, isoleucine and leucine appeared to be the key amino acids sought by embryos on both days tested. Embryos grown in amino-acid-containing media appeared morphologically normal and their volume increased compared with embryos cultured in the absence of amino acids. PMID- 7799309 TI - Progestin content and biosynthetic potential of the corpus luteum of the African elephant (Loxodonta africana). AB - The aim of this study was to examine the progestin content and biosynthetic potential of the corpus luteum of the African elephant (Loxodonta africana). Luteal tissue was collected from nonpregnant and early, mid- and late pregnant elephants (n = 2 per group) shot in the Kruger National Park. Pieces of individual corpora lutea (2-3 per animal; 23 in total) were stored directly in ethanol before hormone analysis. Matching tissue pieces were incubated for 2 h with [3H]pregnenolone (2 x 10(5) c.p.m.), after which tissue plus medium were also stored in ethanol. Progesterone and 17 alpha-hydroxyprogesterone immunoreactivity in tissue extracts were determined by enzymeimmunoassay and radioimmunoassay, respectively, before and after reverse phase HPLC. Progesterone immunoreactivity predominated over that of 17 alpha-hydroxyprogesterone in all corpora lutea examined but concentrations of both hormones were very low (73-374 ng g-1 and 3-93 ng g-1, respectively after HPLC). There were no obvious differences in hormone concentrations in corpora lutea from animals at different reproductive stages. Progesterone and 17 alpha-hydroxyprogesterone immunoreactivity assayed before HPLC was 10-30 times higher than that measured after chromatographic separation. HPLC consistently revealed two large immunoreactive peaks associated with relatively nonpolar compounds, which together accounted for most (at least 75%) of all progesterone immunoreactivity measured. Large amounts of radioactivity with the same retention times as these peaks were also detected after HPLC in samples incubated with [3H]pregnenolone. Analysis of conversion products from four corpus luteum incubations indicated that between 52% and 84% of [3H]pregnenolone had been converted; 19-33% was accounted for by progesterone, and 12-50% by the two substances represented by the unidentified peaks. Subsequent GCMS analysis identified the two immunoreactive peaks as 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane 3,20-dione (5 alpha-dihydroprogesterone). These results indicate that the major progestins contained within and biosynthesized by corpora lutea of African elephants are 5 alpha-reduced metabolites, and that progesterone and 17 alpha hydroxyprogesterone are quantitatively of minor importance. PMID- 7799311 TI - Plasma concentrations of FSH, LH, thyroid-stimulating hormone and growth hormone after exogenous stimulation with GnRH, TRH and GHRH in Booroola ewes that are homozygous carriers or non-carriers of the FecB gene. AB - The aim of the present study in Booroola ewes, either homozygous (BB) or non carriers (++) of the FecB gene, was to test the specificity of the pituitary responses to exogenous hypothalamic releasing hormones by examining the plasma concentrations of FSH, LH, thyroid-stimulating hormone (TSH) and growth hormone (GH) after injecting the animals with different doses of GnRH, thyroid-releasing hormone (TRH) or growth-hormone-releasing hormone, (GHRH) which were administered on separate occasions. The animals (n = 8 per dose) received 0, 3.1 or 12.5 micrograms of thyroid-releasing hormone and GnRH (i.v.), whereas they (n = 9-13 per dose) received 0, 6.0 or 16.0 micrograms GHRH (i.v.). For each experiment there were no differences between the genotypes in bodymass or age. Gene-specific differences in the mean pretreatment concentrations of plasma FSH (BB > ++; P < 0.05) but not of LH, TSH or GH were noted. After treatment with GnRH, TRH or GHRH, significant effects of dose were noted for all the hormones; however, a gene-specific effect was observed only for FSH in response to GnRH (BB > ++; P < 0.01) with no genotype x dose interaction (ANOVA). For LH, the effects of genotype and the genotype x dose interaction almost reached significance at the 5% level (genotype, P = 0.055; genotype x dose, P = 0.067). For TSH and GH the respective genotype x dose interactions were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799312 TI - Paracrine activities of porcine trophoblastic interferons. AB - Interferon-gamma (IFN-gamma) and a type I IFN (spI IFN) are transiently coexpressed by trophoblastic cells of pig conceptuses at implantation between day 12 and day 20 of gestation. The local effects of these trophoblastic IFNs were examined on endometrial cells and on trophoblast by measuring antiviral activity and the induction of (2',5')-oligoadenylate synthetase activity. Trophoblastic vesicles were shown to be susceptible to infection by vesicular stomatitis virus and transmissible gastroenteritis virus. Vesicular stomatitis virus multiplied by about 1000 times in trophoblastic vesicles, and endogenous trophoblastic IFNs or exogenous recombinant IFN-gamma or spI IFN had no effect on virus production. No (2',5')-oligoadenylate synthetase activity could be measured on the trophoblast, even after treatment with IFN-gamma or spI IFN. These results clearly show that trophoblastic IFNs cannot induce antiviral resistance or (2',5')-oligoadenylate synthetase activity in the trophoblast, suggesting that these IFNs have no autocrine function. Endometrial epithelial and stromal cells in primary cultures displayed distinct sensitivity to the antiviral effect of IFN-gamma and spI IFN. Stromal fibroblasts were highly sensitive to spI IFN but weakly sensitive to IFN gamma; epithelial cells were sensitive to both IFNs. The same sensitivity pattern was obtained when measuring the (2',5')-oligoadenylate synthetase activity. Flushing fluid, containing IFN-gamma and type I IFN, was a potent inducer of antiviral effect and (2',5')-oligoadenylate synthetase activity. It is therefore postulated that the endometrial epithelium is the most likely target of trophoblastic IFNs. It is possible that these IFNs play a role in the viral protection of conceptuses. PMID- 7799313 TI - Absence of normal sexual dimorphism of the genitofemoral nerve spinal nucleus in the mutant cryptorchid (TS) rat. AB - Sexual dimorphism of the genitofemoral nerve spinal nucleus has been demonstrated in normal rodents. Calcitonin gene-related peptide is a neurotransmitter, present in the genitofemoral nerve, that has been implicated in the regulation of gubernacular migration and inguinoscrotal testicular descent. A combination of retrograde fluorescent labelling of the genitofemoral nerve and immunohistochemistry for calcitonin gene-related peptide was used in 1-3-day-old mutant TS rats with 85% incidence of congenital cryptorchidism and an absence of the normal sexual dimorphism of the genitofemoral nerve spinal nucleus was demonstrated. There was no significant difference between male and female nuclei with respect to fluorescent-labelled neurones as well as those immunoreactive for calcitonin gene-related peptide, in contrast to an obvious sexual dimorphism present in normal control animals. This lack of normal sexual dimorphism of the genitofemoral nerve nucleus is likely to be important in the pathogenesis of cryptorchidism in this animal model. PMID- 7799314 TI - Histomorphology, oLH and hCG receptors, and testosterone secretion in vitro in Rambouillet rams from lines in which females had been selected for low or high reproductive rate. AB - The objective of this study was to determine whether gross or histomorphological components of the testes, capacity and dissociation constants (Kd) of testicular oLH and hCG receptors, and gonadotrophin-stimulated testosterone secretion in vitro differed among Rambouillet rams from lines selected for low or high female reproductive rate and from rams of a random-bred control line. Lines had been selected for approximately 20 years. Data were collected from 22-month-old rams during the late breeding season. Rams among lines did not differ (P > 0.05) in gross testicular characteristics or most histomorphological characteristics. However, the percentage volume of interstitial vascular tissue was greater (P < 0.05) for rams from lines selected for low female reproductive rate than for rams from lines selected for high female reproductive rate. Receptor sites per Leydig cell and binding capacities of oLH and hCG receptors per testis, per gram of parenchyma, and per milligram of membrane protein did not differ (P > 0.05) among lines. The Kd values for oLH and hCG receptors did not differ (P > 0.05) among lines; however, receptor sites per Leydig cell, capacities of testicular parenchyma to bind gonadotrophin and Kd values were higher (P < 0.05) for oLH than for hCG receptors. Total oLH- and hCG-stimulated testosterone secretion in vitro did not differ (P < 0.05) among lines. In conclusion, selection for or against reproductive rate in Rambouillet ewes has not altered gross or most histomorphometric characteristics of the testes of male offspring, with the exception that selection against reproductive rate increased the proportion of testicular volume occupied by vascular tissue within the interstitium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799316 TI - Mechanisms controlling corpus luteum function in the rhesus monkey (Macaca mulatta): inhibitory action of hCG on luteolysis induced by PGF2 alpha. AB - The aim of this study was to determine whether daily increasing doses of hCG could overcome luteal regression induced by PGF2 alpha in rhesus monkeys. Prostaglandin F2 alpha (10 ng microliters-1 h-1) or vehicle (tham buffer; 1 microliter h-1) was infused directly into the corpus luteum for 7 days, beginning 7 days after the preovulatory oestradiol surge. hCG was injected i.m. in increasing doses (15, 30, 60, 90, 180, 360 and 720 iu) for 7 days, starting on the eighth day after the preovulatory oestradiol surge, or 1 day after the initiation of luteal infusion of PGF2 alpha or vehicle. Monkeys receiving vehicle plus hCG on the same days served as controls. Daily progesterone, oestradiol and hCG concentrations were determined from blood drawn from the saphenous or femoral vein, and the duration of the luteal phases were recorded. Where intraluteally infused PGF2 alpha resulted in premature, functional luteolysis, hCG always inhibited the luteolytic effect of PGF2 alpha; the secretory patterns of progesterone and oestradiol were augmented, and peak values were reached in concert with the highest concentration of hCG in the blood, and the luteal phase was significantly increased compared with those of untreated monkeys or with monkeys treated with PGF2 alpha alone or vehicle. Treatment with hCG alone or with PGF2 alpha vehicle also resulted in maintained luteal function and a significantly longer luteal phase, but both progesterone and oestradiol concentrations began to decline before hCG reached peak values in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799315 TI - Effect of parathyroid hormone-related protein (PTHrP) on the contractility of the myometrium and localization of PTHrP in the uterus of pregnant rats. AB - The effect of parathyroid hormone-related protein (PTHrP) on the contractility of uterine segments taken from pregnant rats and the localization of PTHrP in the uterus during pregnancy were investigated. PTHrP(1-34) had a potent inhibitory effect on spontaneous contractions of the longitudinal layer of uterine myometrium taken from rats at day 4 of pregnancy (IC50 1.6 nmol l-1). In low calcium De Jalon's solution, it also decreased base-line tension (IC50 1.5 nmol l 1) in a concentration-dependent manner. The effect of PTHrP(1-34) on uterine motility decreased as pregnancy progressed until day 13, after which PTHrP(1-34) had no measurable effect on uterine contractility. In contrast, PTHrP(1-34) had no effect on the contractions of the circular smooth muscle of the uterus at any stage of pregnancy. PTHrP(50-69) had no effect on the contractility of either muscle layer of the myometrium. A temporal pattern of staining for PTHrP in the uterus of pregnant rats was observed, and the changes in the staining patterns in the endometrium and myometrium were different in each layer. These data suggest that PTHrP may have at least two distinct roles in the uterus, a relaxing action on longitudinal muscle that depends on the hormonal state of the rat and a novel effect either intraluminally or within the endometrial layer. PMID- 7799317 TI - Effects of sensory stimuli on the incidence of fetal resorption in a murine model of spontaneous abortion: the presence of an alien male and postimplantation embryo survival. AB - Pregnancy outcome may be altered by both genetic and environmental factors. The mating of CBA/J female mice with DBA/2 males normally results in pregnancies characterized by a relatively high incidence of early embryo compared with most other syngeneic or allogeneic matings. This study addressed the role of normal laboratory stress in the induction of early embryo loss. The previously studied 'Bruce effect' describes the total loss of preimplantation embryos (pregnancy block) that is apparently caused by the stress induced by the presence of an alien male and mediated by neuroimmunological effects on prolactin activity. To determine whether this effect could be responsible for the high incidence of postimplantation embryo losses in the CBA/J x DBA/2 model, the original DBA/2 male was replaced on day 6 of gestation by another DBA/2 male, a CBA/J, a C57Bl/6 or a BALB/c male. The relatively high incidence of embryo loss was not affected by removing the original DBA/2 male or introducing another DBA/2 or a CBA/J male, indicating that stress induced by an alien male did not increase the postimplantation losses in this model. Furthermore, the introduction of a DBA/2 male to a CBA/J female that had been mated with a BALB/c male did not elicit early embryo loss. However, the replacement of the original DBA/2 male by a BALB/c male dramatically reduced the incidence of early embryo loss in pregnant CBA/J female mice. The introduction of a C57Bl/6 male also reduced embryo loss but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799318 TI - Seasonal effects on seminal and endocrine traits in the captive snow leopard (Panthera uncia). AB - The annual reproductive cycle of the male snow leopard (Panthera uncia) was characterized by evaluating seminal and endocrine traits monthly. Testicular volume was greatest (P < 0.05) during the winter months when the quality of ejaculate was optimal. Ejaculate volume, total sperm concentration ml-1, motile sperm concentration per ejaculate, sperm morphology and sperm motility index were lowest during the summer and autumn months compared with the winter and spring. Peripheral LH, FSH and testosterone concentrations were also lowest during the summer months, increasing during the autumn just before the increase in semen quality, and were maximal during the winter months. There was a direct relationship (P < 0.01) between: (1) testosterone and testicular volume, total sperm concentration ml-1, motile sperm concentration per ejaculate and ejaculate volume, and (2) LH and testicular volume and motile sperm concentration per ejaculate. In summary, although spermatozoa were recovered throughout the year, optimal gamete quality was observed during the winter and spring. Although previous studies in felids have demonstrated seasonal effects on either seminal or endocrine traits, this is the first study to demonstrate a distinct effect of season on both pituitary and testicular function. PMID- 7799319 TI - Growth-related changes in testicular mass and plasma testosterone concentrations in long-finned pilot whales, Globicephala melas. AB - Blood samples and testes were collected from long-finned pilot whales (Globicephala melas) off the Faroe Islands at irregular intervals over a period of 3 years (July 1986-December 1989). Changes in testis mass (n = 674) and plasma testosterone concentrations (n = 214), measured by radioimmunoassay, were examined with respect to age, bodylength and bodymass of the animals. Corresponding to a rapid testicular growth (from 0.25 kg up to 1.9 kg), puberty occurred in male pilot whales of 4.6-5.7 m in bodylength, 1.2-1.9 tonnes in bodymass and 11-22 years of age. Changes in plasma testosterone concentrations confirmed this result, with very low values (< 2 ng ml-1) in immature animals (testis mass < 0.2 kg), followed by a sharp increase (from 2 to 29 ng ml-1) during the pubertal period, and the maintenance of high concentrations with large variability (> 1.5 ng ml-1 to 14 ng ml-1) in mature males. Testosterone concentrations were significantly correlated with testis mass (P < 0.001), but not with bodylength or age, and very large individual variations were observed in mature males. The average age, length and mass at the attainment of sexual maturity were estimated at 16.99 +/- 0.30 years, 5.162 +/- 0.013 m and 1.403 +/- 0.005 tonnes, respectively. PMID- 7799320 TI - Differences in blood flow to uterine segments and placentae in relation to sex, intrauterine location and side in pregnant rats. AB - The effects of location within the left or right uterine horn, position within each uterine horn, and fetal sex on fetal bodymass, blood flow to individual uterine segments associated with fetuses, and blood flow to the maternal portion of the placenta were investigated in rats. Sprague-Dawley rats were anaesthetized on day 5, 10, 15, 20, 21 or 22 of pregnancy, and radioactive microspheres with diameters of 15 mm were injected via a left ventricular cannula to measure blood flow to tissues. Tissues were weighed wet, and the rate of blood flow, corrected for wet mass (ml min-1 g-1 tissue), was calculated. Microspheres were not detected in fetuses, suggesting that they did not pass from maternal into fetal blood. Uterine blood flow was greater at the cervical and ovarian ends than in the middle of the uterus; on day 15 the rate of blood flow at the cervical and ovarian ends of each uterine horn was over twice that in the middle. The blood flow to the right uterine horn was greater than to the left horn. Blood flow to placentae increased dramatically between day 15 and day 20. There were marked differences in architecture between the uterine artery feeding the ovarian end of the right and left uterine horn, and blood flow to placentae located at the ovarian end of the right uterine horn was greater than to placentae in the same location in the left uterine horn. The blood flow to placentae and fetal bodymass were greater for female than for male fetuses on day 20, but on day 22 the reverse was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799321 TI - Serum zinc and copper concentrations in relation to spontaneous abortion in cows: implications for human fetal loss. AB - The purpose of this study was to investigate the effect of the status of dietary zinc and serum zinc and copper concentrations on the risk of fetal loss in 570 cows. three herds received no supplements (herds 1, 3, 4), while cows in herd 2 received supplements of either 7 g zinc week-1 (n = 118), as zinc methionine, or a control diet containing methionine (n = 128). Serum zinc, copper and metallothionein concentrations were determined once a month throughout gestation. Logistic regression and survival analysis were used to examine for associations between risk of fetal loss and serum zinc, copper, copper:zinc, or metallothionein concentrations, supplement level, and maternal age at conception. The risk of fetal loss increased when both serum zinc decreased and copper concentrations increased (P < 0.0001; relative risk = 10.28, 95% confidence intervals = 4.69, 22.5). The attributable risk, for a decline in the zinc concentration by 10 mumol l-1 and an increase in the copper concentration by 5 mumol l-1 was 90.27%. Methionine-supplemented cows had a higher risk of fetal loss compared with zinc-methionine-supplemented cows (one-tailed P = 0.0375; relative risk = 2.98). Cows in herds 1, 3 and 4 had a higher risk for abortion than did zinc-methionine-supplemented cows in herd 2 (relative risk = 26.27, 95% confidence intervals = 2.31, 299.38; relative risk = 40.87, 95% confidence intervals = 3.50, 458.43; relative risk = 41.53, 95% confidence intervals = 3.77, 457.02, respectively). Our results suggest that inflammation and zinc nutriture may play an important role in fetal loss in dairy cows. PMID- 7799322 TI - Differential effects of LH and PGE2 on progesterone secretion by small and large porcine luteal cells. AB - This study examined the effects of LH and PGE2 on progesterone secretion by small and large porcine luteal cells with or without low-density lipoproteins. Corpora lutea were isolated from gilts 13-14 days after administering gonadotrophins; enzymatically dissociated and small and large cells were isolated by elutriation. Culture plates, 24-well, were then seeded with 150,000 small or 30,000 large luteal cells suspended in 1 ml M199 medium supplemented with 5 micrograms insulin ml-1, 40 ng hydrocortisone ml-1 and with or without low-density lipoproteins (50 micrograms cholesterol ml-1) or PGE2. Cells were cultured for up to 24 h in a humidified incubator at 37 degrees C under 5% CO2 in air. The low-density lipoproteins stimulated (P < 0.05) progesterone secretion by large, but not small, luteal cells. Prostaglandin E2 stimulated (P < 0.05) progesterone production by large luteal cells in a dose-dependent manner, and the stimulatory effects of PGE2 were greater (P < 0.05) in the presence than in the absence of low-density lipoproteins. Progesterone secretion by small luteal cells was not significantly affected by PGE2. Progesterone production by small luteal cells was enhanced (P < 0.05) by LH, and the stimulatory effects of LH were greater (P < 0.05) in the presence than in the absence of low-density lipoproteins. In the absence of these lipoproteins, LH had no effect on progesterone secretion by large luteal cells; however, in the presence of low-density lipoproteins, LH increased (P < 0.05) progesterone secretion by large cells, though to a lesser (P < 0.05) extent than the effect of LH on small cells. These data demonstrate that progesterone secretion by porcine luteal cells is stimulated differentially by LH and PGE2 and that small luteal cells are more responsive to LH and PGE2 acts primarily on large luteal cells. PMID- 7799323 TI - 3 beta-Hydroxysteroid dehydrogenase activity and gestagen concentrations in bovine cotyledons and caruncles during gestation and parturition. AB - 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) activity in bovine cotyledons was much higher than in caruncles throughout the gestation period. The activity of this enzyme in cotyledons increased greatly to 150.6 +/- 5.8 pmol min-1 mg-1 protein during the seventh month of gestation, reached a peak of 221.0 +/- 34.9 pmol min-1 mg-1 protein during the eighth month, and decreased at parturition. Progesterone and 20 alpha-hydroxyprogesterone concentrations in cotyledons also increased sharply to 2.69 +/- 0.30 and 2.15 +/- 0.42 ng mg-1 protein, respectively, during the seventh month of gestation, reaching peaks of 2.86 +/- 0.47 and 2.51 +/- 0.36 ng mg-1 protein, respectively, during the eighth month and decreasing at parturition, in a manner similar to the activity of 3 beta hydroxysteroid dehydrogenase. The fluctuation of 17 alpha-hydroxyprogesterone concentration in cotyledons was different from that of progesterone and 20 alpha hydroxyprogesterone. These findings indicate that the activity of 3 beta hydroxysteroid dehydrogenase in the placenta is enhanced during the third trimester, and progesterone synthesized in the cotyledons is converted concurrently to 20 alpha-hydroxyprogesterone before progesterone is transferred to the fetal blood. PMID- 7799324 TI - Influence of meteorological events on obstetrical data in cattle and swine. AB - In a interdisciplinary scientific cooperation involving human and veterinarian obstetricians and meteorologists, an attempt was made to correlate the obstetrical data of cows and pigs with meteorologically defined weather events. During the observation period of 10 years the parturitions of cattle (n = 645) showed no significant statistical connection to the weather on day of delivery, the day before parturition or the day after. The only significant result in cattle was a shortening of the gestation period by 4.9 days in a group of cows that went into labour on, or after, the sixth day of a constant weather situation. Significant variations in the duration of gestation in swine (n = 786) were related to the weather on the day of delivery; central high-gradient anticyclonic spring, summer and autumn weather was linked to an extension of the pregnancy by nearly 1 day, while cyclonic central low-gradient weather during autumn was related to a shortening of pregnancy by approximately 1 day. The weather on the day before parturition was also correlated with the duration of gestation in swine. In this respect, low-gradient cyclonic autumn weather coincided with gestation periods that were reduced by 0.95 days, while central anticyclonic winter and spring weather coincided with extensions of gestation of 0.98 and 1.12 days, respectively. Compared with labour during low-gradient anticyclonic weather, the course of labour in pigs was significantly protracted by approximately 1.5 h during low-gradient cyclonic weather. Weather fronts on the day before, the day after or on the day of labour had no influence on the gestation and parturition data collected in either species. PMID- 7799325 TI - Characterization of freshly dispersed porcine myometrial cells: evidence for voltage-dependent Ca2+ channels and regulatory receptors. AB - A patch-clamp study of Ca2+ currents and spectrofluorometric detection of the intracellular Ca2+ concentration [Ca2+]i was performed on porcine myometrial cells that had been isolated by collagenase. Isolated myometrial cells were the typical long cylinder shape. The main length and diameter of myometrial cells were 505 +/- 20 and 11 +/- 0.5 microns (n = 40), respectively, in the prepartum period and 265 +/- 22 and 7 +/- 0.4 microns (n = 40), respectively, in the luteal phase. Immunocytochemistry with an antibody against desmin stained 90% of the cells positively, and about 95% of the cells excluded Trypan blue dye. The basal [Ca2+]i of myometrial cells in the luteal phase and the prepartum period was 119 +/- 12 (n = 30) and 154 +/- 31 nmol l-1 (n = 48), respectively. In prepartum myometrial cells, oxytocin (10(-7) mol l-1) and carbachol (10(-4) mol l-1) increased [Ca2+]i in a biphasic pattern, with a sharp peak followed by a plateau. In cells in the luteal phase, adrenaline (10(-7) mol l-1) plus propranolol (10( 6) mol l-1) produced a biphasic increase in [Ca2+]i. However, in the absence of propranolol, the increase in [Ca2+]i by adrenaline was small. Prostaglandin F2 alpha (10(-6) mol l-1) induced a monophasic increase in the [Ca2+]i in cells in the luteal phase. By depolarizing the cells from -30 to +50 mV from a holding potential of -50 mV, Ca2+ currents were evoked with a threshold at -20 mV, reaching a maximum between 10 and 30 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799326 TI - Effects of progesterone pretreatment on the oxytocin receptor concentration and the response to oxytocin during the simulated early luteal phase in the ovariectomized ewe. AB - A steroid-treated ovariectomized ewe model was used to investigate the role of progesterone pretreatment in the control of functional oxytocin receptor concentrations during the early luteal phase. Ovariectomized ewes (n = 28) were injected with oestradiol for 2 days (final injection = day 0) with or without progesterone pretreatment (progestagen sponge for 10 days). Ewes were then given high or low concentrations of progesterone combined with high, low or zero concentrations of oestradiol in a pattern known to simulate the early luteal phase profile (n = 4 per group). Ewes were given 1 microgram oxytocin (i.v.) on day 4 and plasma was collected to assay 13,14-dihydro-15-keto PGF2 alpha. The concentration of progesterone and oestradiol administered had no effect on the concentration of 13,14-dihydro-15-keto PGF2 alpha following oxytocin administration (P > 0.05). However, the group that was not pretreated exhibited a small but significant 13,14-dihydro-15-keto PGF2 alpha response in comparison with the equivalent pretreated group (P < 0.05). In a subsequent study, ewes were divided into groups pretreated and not pretreated with progesterone; both groups were given oestrous concentrations of oestradiol and high concentrations of progesterone and oestradiol together. On day 0, 2, 3 or 4, ewes from each group (n = 3, 3, 4 and 4, respectively) were given 1 microgram of oxytocin i.v., and the endometrium was collected to measure the binding of oxytocin receptors. Oxytocin caused a significant (P < 0.05) increase in the concentration of 13,14 dihydro-15-keto PGF2 alpha in all ewes on day 0 but not on days 2, 3 or 4. Oxytocin receptor concentrations were maximal on day 0 and basal by day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799327 TI - Suppression of plasminogen activator production in sheep embryos in vitro after treatment with cycloheximide or ouabain. AB - Effects of the metabolic inhibitors cycloheximide and ouabain on development in vitro and plasminogen activator production by sheep embryos were investigated. Embryos (n = 152) from the eight-cell to the morula stage were surgically collected from naturally mated, oestrus-synchronized and superovulated Polypay ewes. In Expt 1, embryos (n = 104) were grouped by cell stage, cultured in Whitten's medium with 1.5% BSA containing 0, 0.1 or 1.0 microgram cycloheximide ml-1 for 24 h, washed and cultured in this medium for 168 h. In Expt 2, morulae (n = 48) were cultured for 48 h in Whitten's medium with 1.5% BSA transferred to the same medium containing 0 or 1.0 mmol ouabain l-1 and cultured for 24 h, and then washed and cultured in this medium for 120 h. At 24 h intervals in both experiments, the medium was recovered and analysed for plasminogen activator. In Expt 1, eight-cell embryos underwent limited development; little difference in the production of plasminogen activator due to cycloheximide treatment was therefore observed. Compared with medium without cycloheximide, treatment with 1.0 microgram cycloheximide ml-1 reduced the number of 16-cell embryos (P < 0.05) and morulae (P < 0.05) (60% versus 10% and 77% versus 8%, respectively) that began to hatch. The mean production of plasminogen activator was greatest in embryos cultured initially as morulae compared with that of 16-cell and eight cell embryos (P < 0.05). Cycloheximide treatment suppressed the mean production of plasminogen activator in a dose-dependent manner (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799328 TI - Isolation of cell populations from the mare corpus luteum: comparison of mechanical and collagenase dissociation. AB - Corpora lutea were obtained from mares at days 3, 10 and 14 after ovulation, and examined histologically. The morphology of isolated luteal cells obtained by either mechanical or collagenase dissociation of the tissue was examined and the cells stained to detect the steroidogenic enzyme delta 5, beta-hydroxysteroid dehydrogenase. The ratio of large:small cells was significantly higher for cells obtained from mechanically dissociated luteal tissue than for cells obtained by collagenase dissociation (P < 0.01). Cells obtained by both mechanical and collagenase dissociation secreted progesterone, although neither cell population responded to exogenous gonadotrophin with an increase in progesterone secretion. Homogenates of equine luteal tissue bound 125I-labelled human LH with high affinity and specificity, and the specific activity and binding affinity of luteal LH receptors did not change significantly from day 3, to days 10 and 14 after ovulation. However, mechanically dissociated cells on days 10 and 14 bound significantly more LH than did collagenase-dissociated cells on these days (P < 0.05). These results indicate that (i) collagenase dissociation of mare luteal tissue yields a population of cells that is unrepresentative of the corpus luteum, and (ii) the mare corpus luteum is not responsive to LH in vitro at the stages examined. PMID- 7799329 TI - Preparation of highly purified porcine theca cells. AB - A novel method for purifying dispersed porcine theca cells, with less than 3% granulosa cell contamination, was developed by the repeated use of mechanical and enzymatic procedures. The steroidogenic criteria used for the identification and purity evaluation of both theca and granulosa cells were also improved. Purified theca and granulosa cells from medium-sized follicles displayed steroidogenic differences when they were cultured in the presence of 10% fetal bovine serum: (1) the theca cells synthesized oestradiol (239.1 +/- 35.1 pg ml-1 per 2.5 x 10(5) cells in 40 h), but the granulosa cells did not synthesize it unless aromatizable androgens were added; (2) theca cells synthesized androstenedione (73.2 +/- 14.4 ng ml-1 per 2.5 x 10(5) cells in 40 h), but granulosa cells did not; (3) FSH did not affect progesterone production in theca cells; (4) the theca cells secreted androstenedione for up to 48 h; and (5) FSH significantly stimulated progesterone production in granulosa cells during a culture for 40 h (P < 0.05), but not during culture for 12 h. The lack of response to FSH was used as a reliable, functional indicator of the purity of porcine theca cells. However, this criterion proved not to be useful for cells cultured for 12 h; porcine FSH had no effect on the progesterone production of theca cells co cultured for this time with as many as 20% granulosa cells. However, after co culturing for 40 h, this criterion resulted in the detection of only 3% granulosa cell contamination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799330 TI - Cholesterol, phospholipid and phospholipase activity of ampullary and isthmic fluid from the bovine oviduct. AB - Cholesterol and phospholipid concentrations and phospholipase activity were measured in fluid from cannulae collected from the bovine oviductal isthmus and ampulla at different stages of the oestrous cycle. The cholesterol concentration and cholesterol normalized by protein were significantly (P = 0.03) greater in isthmic oviductal fluid (224.3 +/- 42.7 micrograms ml-1 over all stages) than in ampullary oviductal fluid (164.5 +/- 11.3 micrograms ml-1), and maximal concentrations (284.5 +/- 25.5 micrograms ml-1) were found during the luteal stage (serum progesterone concentration > or = 1.5 ng ml-1). The concentrations of the phospholipids sphingomyelin and lysophosphatidylcholine increased at different stages of the cycle and in different regions. In the ampulla, the concentration of sphingomyelin was significantly (P < 0.05) greater in oviductal fluid collected during the luteal phase (12.1 +/- 2.7% of total phospholipids) than in fluid collected near oestrus and ovulation (7.5 +/- 1.5% and 6.9 +/- 1%, respectively). The concentration of lysophosphatidylcholine was greater (P < 0.01) in ampullary (19.2 +/- 1.6% of total phospholipids) than in isthmic oviductal fluid (9.9 +/- 1.1%) collected near ovulation. The ratio of cholesterol to total phospholipid was highest in oviductal fluid collected from the isthmus during all stages (2.3 micrograms ml-1:% total phospholipid), while the minimal ratio was found in ampullary fluid collected near ovulation (1.5). Phospholipase activity was higher (P = 0.03) in isthmic oviductal fluid (20.4 +/- 3.2% product formed) than in ampullary oviductal fluid (14.6 +/- 1.4%); the lowest activity (12.6 +/- 1.7% product formed) was in fluid collected during the phase of the oestrous cycle immediately before ovulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799331 TI - Ovarian follicular development and endocrine responses in follicular-fluid treated and hemi-ovariectomized heifers. AB - The effects of charcoal-extracted bovine follicular fluid (BFF) on endocrine profiles and follicular development in intact and hemiovariectomized postpubertal heifers were examined. Oestrus-synchronized heifers received Norgestomet implants on day 1 and 7 of treatment and were then injected s.c. with 11 ml saline (control) or 11 ml BFF twice a day for 12 days. The ovary bearing the largest follicle (OV1) was removed on day 7 and the remaining ovary (OV2) was collected on day 13. Follicles were observed by daily ultrasonography and were classified according to diameter (size 1: 2-3 mm; size 2: 4-6 mm; size 3: 7-10 mm; size 4: > 10 mm). After ovariectomy they were classified by diameter and histologically as normal or atretic. Intact control heifers had increased numbers of size 4 follicles on OV1 on days 6 and 7; no increase was observed in BFF-treated heifers (P < 0.03). In BFF-treated heifers, the mean basal LH concentration was higher (P < 0.05) and that of FSH was lower (P < 0.04) than in controls. FSH concentrations in BFF-treated heifers decreased from 0.60 +/- 0.08 ng ml-1 (day 1) to 0.22 +/- 0.05 ng ml-1 (day 7; P < 0.04). The concentration of oestradiol increased in control heifers, but not in BFF-treated heifers (P < 0.001). After hemicastration, OV2 underwent compensatory hypertrophy in control heifers, with an increase in the number of size 2, 3 and 4 follicles (P < 0.05), whereas BFF treated heifers did not. Thus, total follicular volume was much lower in BFF treated than in control heifers on day 13 (92.2 +/- 15.4 versus 1393.8 +/- 276.6 mm3; P < 0.0002). A transient increase in FSH (P < 0.006) and oestradiol (P < 0.01) concentrations occurred after hemiovariectomy in control but not in BFF treated animals. In control heifers, an analysis of temporal relationships showed negative correlations between the volume of size 3 and size 4 follicles, and between FSH concentrations and the volume of size 3 and 4 follicles. A positive correlation was found between the mean diameter of the largest follicle and the concentration of oestradiol, whereas negative relationships were found between the concentrations of FSH and oestradiol, and between FSH and the mean diameter of the largest follicle. Analysis of the histological data showed that the number and volume of follicles > 8.57 mm was lower in the BFF-treated OV1 ovary, whereas no differences were found for follicles < or = 8.57 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799332 TI - Attempts to apply curve fitting models to the analysis of progression of radiographic damage in rheumatoid arthritis are laudable, but are the results believable? PMID- 7799333 TI - Advantages and limitations of ultrasound in the evaluation of the rheumatoid shoulder. PMID- 7799334 TI - Increased type I collagen degradation in early rheumatoid arthritis. AB - OBJECTIVE: To evaluate the serum concentration of the mature, crosslinked carboxy terminal telopeptide of type I collagen (ICTP) in patients with early onset rheumatoid arthritis (RA) and to assess its correlation with clinically relevant features of the disease. METHODS: The serum ICTP concentration was measured in 99 adult patients with RA with a duration of disease less than one year. The main clinical outcome measures were joint count, modified Lansbury index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Larsen index and number of erosions in peripheral joints. RESULTS: There was a strong positive correlation (p < 0.001) between the serum ICTP concentration and the Lansbury joint index and a weaker but still significant correlation (p < 0.01) between the serum ICTP concentration and the number of eroded hand and foot joints. CONCLUSION: Serum ICTP may have value as a marker of tissue destruction in patients with early RA. PMID- 7799335 TI - Human mucosyl lymphocyte marker expression in synovial fluid lymphocytes of patient with rheumatoid arthritis. AB - OBJECTIVE: Human mucosyl lymphocyte marker (HML-1) antigen is an activation antigen and adhesion molecule of the beta 7 integrin family, which is generally restricted to T cells found in the intestinal epithelium. Expression of the membrane antigen as defined by the monoclonal antibody HML-1 was studied on peripheral blood (PB) lymphocytes and synovial fluid (SF) lymphocytes in 10 patients with rheumatoid arthritis (RA) and in a control group of patients with osteoarthritis (OA). METHODS: Double fluorescence activated flow cytometry was used to assess HML-1 expression with T cell subtype antigens (CD3, CD4, CD8) or activation markers interleukin 2 receptor (IL-2R) (CD25), HLA-DR, and lymphocyte function associated antigen (LFA-1) (CD11a) were assessed by flow cytometry. RESULTS: HML-1 antigen expression in PB lymphocytes of patients with RA (7.3%) was found to be comparable to the control group (6.4%). In contrast, 25.4% (range 14-43%) of SF lymphocytes expressed HML-1 antigen, compared to 13.6% of SF lymphocytes in patients with OA (p < 0.001). In RA, 62% of HML-1 positive cells from SF lymphocytes were the CD8 subtype, compared to 10.6% of PB lymphocytes (p < 0.003), and 18% of control SF lymphocytes (p < 0.05). Furthermore, HML-1 antigen and HLA-DR antigen were coexpressed in 75% of RA SF lymphocytes compared to 29.6% of control SF lymphocytes (p < 0.01). In contrast, coexpression of LFA-1 and the Il-2R did not differ from that of control. CONCLUSION: We describe overexpression of the adhesion molecule HML-1 in SF lymphocytes of patients with RA, preferentially in the CD8 subset. These results suggest a similarity between the expression of activation antigens in SF lymphocytes of patients with RA and T lymphocytes present in the intestinal epithelium. PMID- 7799336 TI - Phenotypic characteristics of bone marrow cells in patients with rheumatoid arthritis. AB - OBJECTIVE: Our previous study showed the presence of abnormal myeloid lineage cells in the epiphyseal bone marrow adjacent to joints affected with severe rheumatoid arthritis (RA). Now, we investigated whether there were any changes of other marrow cell populations related to RA, and whether there were any pathologically characteristic changes in the iliac bone marrow, which is one of the major systemic hematopoietic organs. METHODS: 2-Color flow cytometry was carried out to analyze the phenotypes of mononuclear cells (MNC) fractions in bone marrow aspirates and venous blood from 56 patients with RA and 7 non-RA controls. RESULTS: The absolute number of MNC in the iliac bone marrow was increased by 3-fold in the RA patients compared with the non-RA controls. In contrast, no significant increase of MNC was observed in the tibial epiphyseal bone marrow or peripheral blood. The ratio of each MNC fraction in the iliac bone marrow did not differ significantly between the RA patients and the non-RA controls. In lymphocyte subsets, the percentage of HLA-DR+CD8+ cells to all CD8 cells in the iliac bone marrow increased significantly in the RA patients compared with the non-RA controls. Abnormal myeloid cells (MX-GA+MY4+ cells), specific to severe RA, were found to be more concentrated in the iliac bone marrow than in the tibial epiphyseal bone marrow. CONCLUSION: Characteristic pathologic changes of the iliac bone marrow suggest an important role of systemic bone marrow in the progression of RA. PMID- 7799337 TI - In vivo analysis of disease modifying drug therapy activity in rheumatoid arthritis by sequential immunohistological analysis of synovial membrane interleukin 1 beta. AB - OBJECTIVE: To assess sequential changes of synovial membrane interleukin 1 beta (IL-1 beta) in patients with rheumatoid arthritis receiving chrysotherapy and glucocorticoids. METHODS: Sequential synovial biopsies taken before and after 2 and 12 weeks of treatment were analyzed by immunohistological techniques. RESULTS: Significant decreases in IL-1 beta staining occurred in biopsies taken after 12 weeks' chrysotherapy, while mononuclear cell numbers were unchanged. Results were similar in patients receiving glucocorticoid and gold, and in those receiving gold alone. CONCLUSION: These data suggest that chrysotherapy reduces IL-1 beta production in vivo, a property that has been shown in vitro, and that this change precedes changes in synovial membrane mononuclear cell numbers. PMID- 7799339 TI - Progression of erosion and joint space narrowing scores in rheumatoid arthritis assessed by nonlinear models. AB - OBJECTIVE: To determine whether the first order kinetics model or the function proportional to the square root of disease duration better represents the progression of radiographic damage according to the disease duration than a linear model in rheumatoid patients. METHODS: Two hundred twenty-eight patients assessed at a single time point were studied by using 2 nonlinear models of radiographic damage. In 44 patients a second radiographic analysis was taken within a 3-year period. RESULTS: In this data set, both models reveal the highest rate of progression in the first 3 years of the disease. The square root of the disease duration seems to better depict the whole disease course. CONCLUSION: Nonlinear models should be compulsory in the assessment of radiographic damage, especially when slow acting antirheumatic drug effects after 5 years of disease duration are studied. PMID- 7799338 TI - The severity of rheumatoid arthritis: a 6-year followup study of younger women with symptoms of recent onset. AB - OBJECTIVE: In rheumatoid arthritis (RA), not only outcome measurements taken at a single point in time, but also the severity during the entire disease period is important. In this investigation we measured severity in terms of the course of disease activity. It is the activity of the disease which leads to most suffering in the patient, and which we try to alleviate. METHODS: Patterns of disease activity were investigated in 132 female patients who were followed yearly from an early phase of the disease for a mean duration of 6 years. RESULTS: Sixty seven patients (50.8%) continuously had < or = 4 swollen joints (low activity), 23 patients (17.4%) continuously had > or = 4 swollen joints (high activity), in 10 patients (7.6%) disease activity decreased from high to low, in 8 patients (6.1%) disease activity increased from low to high, and 24 patients (18.2%) had fluctuating levels of disease activity. The outcome of the disease as measured by the functional ability, the radiological abnormalities, and number of prescribed 2nd line drugs, was best in patients with continuously low levels of disease activity, and worst in patients with continuously high or increasing levels of disease activity. CONCLUSION: For about half of the female patients presenting to a rheumatology outpatient clinic, the severity of RA after 6 years of disease duration is characterized by continuous but low disease activity, and sufficient preservation of functional ability. For the other half of the patients RA is a progressive and disabling disease. PMID- 7799340 TI - Cyclosporine in common clinical practice: an estimation of the benefit/risk ratio in patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate in common clinical practice the toxicity/efficacy ratio of low dose cyclosporine A (CsA) in patients with advanced rheumatoid arthritis (RA) after 12 months CsA administration. METHODS: One hundred and two patients with RA were included in the study. The initial dose of CsA was 2.5 mg/kg/day, the mean maximum dose was 3.2 mg/kg/day and the dose at 12 months was 2.8 mg/kg/day. RESULTS: Sixty-nine (68%) patients completed 12 months of treatment. Seventeen (17%) patients discontinued for lack of efficacy and 16 (16%) for toxicity (of which 50% for gastrointestinal intolerance). The clinical efficacy variables improved significantly by 36-42% between entry and Month 6 and remained stable thereafter. The C-reactive protein decreased from 43 U/ml at entry to 22 U/ml (p < 0.0001) at 12 months. Forty-four percent of the patients and 47% of the physicians judged the efficacy as good or very good. The median number of adverse events/patient was 3 but most adverse events were either not clinically important or disappeared after dose reduction. Gastrointestinal (GI) intolerance and nephrotoxicity (> 30% increase in serum creatinine) each occurred in 50% of the patients. GI intolerance was transient in 80% of the patients but accounted for 50% of the premature discontinuations for toxicity. Nephrotoxicity persisted in the 50% of the patients in whom it occurred, despite dose reduction. The mean serum creatinine rose from 70 (13) mumol/l at entry to 86 (23) mumol/l at 12 months (23% increase; p < 0.0001), and this increase had been entirely reached after 3 months. Variables that could significantly predict the occurrence of nephrotoxicity could not be identified. CONCLUSION: CsA can be safely and effectively administered to patients with RA for a duration of at least 12 months. An acceptable renal function at entry, close monitoring of the serum creatinine concentration and dose reductions when appropriate are prerequisities. PMID- 7799341 TI - Intermittent treatment with D-penicillamine is effective in lower doses and with fewer adverse effects in patients with rheumatoid arthritis. AB - OBJECTIVE: To determine whether intermittent rather than daily administration of D-penicillamine (D-Pen) would effectively reduce the incidence of adverse effects without significantly diminishing the clinical benefits. METHODS: We conducted an open prospective trial comparing daily and intermittent schedules. Among 76 Japanese patients with rheumatoid arthritis (RA), 37 underwent daily treatment with D-Pen while 39 were given D-Pen intermittently (every Monday, Wednesday, and Friday). RESULTS: The mean D-Pen dose was 166.8 and 99.4 mg/day for daily and intermittent groups, respectively, the difference being highly significant (p < 0.0001, Mann-Whitney's U test). The incidence of adverse effects was significantly lower in the intermittent group. Both schedules significantly reduced the activity of RA, as evaluated by clinical and laboratory variables. No significant differences were observed in the degree of improvement between the 2 schedules. CONCLUSION: Intermittent therapy with D-Pen is an effective treatment for patients with RA and its higher degree of flexibility can lead to maximum efficacy for management of patients with RA. PMID- 7799342 TI - Ultrasound evaluation of painful rheumatoid shoulders. AB - OBJECTIVE: To provide more information about various types of rheumatoid involvement of the painful shoulder by ultrasonography (US). METHODS: US examinations were performed in 44 patients (88 shoulders) with rheumatoid arthritis (RA). The technique of shoulder ultrasonography was standardized in studies of 30 healthy volunteers (60 shoulders) without shoulder complaints. US findings were compared with clinical, laboratory and radiographic data to find any relationship. RESULTS: Sonography could reveal inflammatory conditions at early stages of RA when no radiographic changes were seen. The most common US finding was subacromial-subdeltoid bursitis in 61 shoulders (69%) of 35 patients. Synovitis in the glenohumeral joint was seen in 51 shoulders (58%) of 32 patients, biceps tendinitis in 50 shoulders (57%) of 29 patients and changes in the supraspinatus tendon in 29 shoulders (33%) of 20 patients. There were multiple rheumatoid symptoms in 61 shoulders (69%), one condition resulted in changes in 17 shoulders (19%) and no visible US findings in 10 shoulders (11%). Clinical findings were rather unspecific. Flexion, abduction and outward rotation were often restricted in shoulder symptoms, whereas inward rotation was rarely limited. Shoulder swelling indicated subacromial-subdeltoid bursitis. CONCLUSION: Ultrasonography is a very useful method for rheumatologists and orthopedists to see inside joints. It can provide remarkable help for local injection therapy and for planning surgery because of its suitability for evaluation of the extent of rheumatoid disease. PMID- 7799344 TI - T cell receptor V alpha repertoire of infiltrating T cells in labial salivary glands from patients with Sjogren's syndrome. AB - OBJECTIVE: To analyze the T cell receptor (TCR) V alpha repertoire of infiltrating T cells in labial salivary glands of patients with Sjogren's syndrome (SS). METHODS: TCR V alpha genes of infiltrating T cells in lips from 2 patients with SS were examined, using the double step inverse polymerase chain reaction. Four and 7 clones encoding the VJC alpha region were established and sequenced, respectively. RESULTS: All 4 clones used the V alpha 17.1 gene in one patient, while 3 (42.8%) of 7 clones from the other patient used the V alpha 2 family gene (V alpha 2.1, V alpha 2.2, V alpha 2.4), and the other 3 clones used the V alpha 11.1 family gene. A comparison using labial salivary glands and peripheral blood showed that the predominant expression of V alpha 2, V alpha 11.1, and V alpha 17.1 gene segments is specific in the salivary glands. CONCLUSION: The TCR V alpha repertoire of infiltrating T cells from the lips of 2 patients with SS was relatively restricted in individual patients, thereby suggesting the limited heterogeneity of these cells in salivary glands. PMID- 7799343 TI - Rheumatic manifestations in patients with myelodysplastic and myeloproliferative diseases. AB - OBJECTIVE: To evaluate the rheumatic complications in patients with myelodysplastic and myeloproliferative diseases. METHODS: A retrospective chart review of patients with a rheumatic disease and either a myelodysplastic or myeloproliferative disorder diagnosed on bone marrow examination. RESULTS: Nine patients were identified, 5 with myelodysplastic and 4 with myeloproliferative disorders. Polyarthritis was the most common rheumatic presentation, occurring in 6 patients with a positive rheumatoid factor in 4. Necrotizing vasculitis complicated the course in 3 patients. Autoantibodies and hypergammaglobulinemia were present in the majority of patients. CONCLUSION: There is an association between hematologic disorders caused by proliferation of bone marrow derived pluripotent stem cells and rheumatic disorders. PMID- 7799345 TI - The prevalence of Sjogren's syndrome in Behcet's syndrome. AB - OBJECTIVE: The role of autoimmune mechanisms in Behcet's syndrome (BS) is debated. Sjogren's syndrome (SS) accompanies most autoimmune diseases. Thus we investigated the prevalence of SS in BS in a formal protocol. METHODS: The study was conducted in 2 phases. During the first phase subjective symptoms of dryness were blindly assessed by questionnaires and Schirmer I and Saxon tests were done in 67 patients with BS and 100 healthy and diseased controls. During the 2nd phase 30 patients with BS and 19 with rheumatoid arthritis (RA) had salivary gland biopsies along with rose bengal dye, Schirmer I and tear breakup time tests. RESULTS: During the first phase only patients with primary SS had significantly abnormal findings. However during the 2nd phase pathologic changes in salivary gland biopsies and positive RB tests were highly significantly more prevalent among patients with RA. CONCLUSION: SS is not a feature of BS. PMID- 7799346 TI - Systemic disease in subacute cutaneous lupus erythematosus: a controlled comparison with systemic lupus erythematosus. AB - OBJECTIVE: We sought to compare the prevalence of systemic disease in subacute cutaneous lupus erythematosus (SCLE) with systemic lupus erythematosus (SLE). METHODS: Clinical and laboratory features of 14 patients with SCLE were compared with 22 age and sex matched controls with SLE. RESULTS: Manifestations other than arthritis and skin disease were present in 11/14 (79%) SCLE cases compared with 19/22 (82%) SLE cases. Severe systemic disease occurred in one-half of patients with SCLE (5/7 men, 1/7 women), and most had the papulosquamous pattern. CONCLUSION: Systemic manifestations may be as varied in SCLE as in SLE, and severe disease is not unusual. In particular, men with papulosquamous SCLE may be at higher risk for severe extracutaneous disease. PMID- 7799347 TI - Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. AB - OBJECTIVE: To evaluate the prevalence of cytoplasmic (c) and peripheral (p) antineutrophil cytoplasmic antibodies (ANCA) using the indirect immunofluorescence (IIF) slide kit (INOVA) in patients with systemic lupus erythematosus (SLE) to correlate the presence of ANCA with disease activity and to determine if ANCA is associated with specific clinical manifestations. METHODS: One hundred and fourteen consecutive patients with SLE seen at The Wellesley Hospital Lupus Clinic, Toronto, Ontario in May and June, 1992 were assessed clinically, and blood drawn for routine serology and ANCA. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). ANCA was measured by IIF. RESULTS: Of the 114 patients, 12 (10.5%) had c-ANCA and 29 patients (25.4%) had p-ANCA. The titers of ANCA varied from 1:20 to 1:160. SLEDAI was 0 in 6 patients (5%), and 108 patients had some disease activity. Eighty eight patients (77%) had mild to moderate active disease (SLEDAI < 10), and 20 (18%) patients had severe active disease (SLEDAI > or = 10). CONCLUSION: No correlation was found between the presence of ANCA and SLEDAI either when analyzed as active-inactive (p = 0.75) or when correlated with degrees of disease activity (1-10: > 10) (p = 0.77). No correlation was found between p and c ANCA and the presence of vasculitis, renal, or CNS disease at the time of the assessment or at any time during the course of the disease. Thus ANCA was not associated with SLE disease activity or the presence of vasculitis in SLE. PMID- 7799349 TI - Association of antimitochondrial antibodies type 5 and anti-beta 2 glycoprotein I antibodies in the antiphospholipid syndrome. AB - OBJECTIVE: To evaluate if antimitochondrial type 5 antibodies (AMA5) might be included among antiphospholipid syndrome (APS) markers. METHODS: In a retrospective study, blood variables of 48 patients with AMA5 were analyzed in relationship with clinical and biological markers of APS and systemic lupus erythematosus (SLE). RESULTS: We observed a high prevalence of false biological test for syphilis (95%), lupus anticoagulant (LAC) (71%), anticardiolipin antibodies (aCL) of IgG (71%) and IgM (75%) isotype, positive direct Coombs' test (54%), thrombocytopenia (52%), anti-B2 glycoprotein I antibodies (38%). Twenty nine patients (61%) had at least one clinical manifestation of APS; 42% had recurrent arterial and/or venous deep thrombosis and 21% had recurrent fetal loss. But, for 2 patients, AMA5 were the sole detected immunological marker. Moreover, SLE was observed in 35% of the patients. These were different from 100 control patients with SLE with the respect to skin involvement and dsDNA antibodies which were less frequent (p < 0.01) and aCL, LAC, false biological test for syphilis (p < 0.001), positive direct Coombs' test and thrombocytopenia (p < 0.05) which were more frequent. CONCLUSION: Our data suggests (1) AMA5 is another marker of the APS (2) in patients with SLE, AMA5 seems to be a marker of a subset of SLE. This appears to justify the routine detection of these antibodies. PMID- 7799348 TI - A 2 year, open ended trial of methotrexate in systemic lupus erythematosus. AB - OBJECTIVE: To investigate a possible role for methotrexate (MTX) in the treatment of patients with systemic lupus erythematosus (SLE) who require unacceptably high doses of glucocorticosteroids (GCS) for control of their disease. METHODS: Twelve patients with SLE participated in this open ended prospective study. Patients with active renal or central nervous system (CNS) disease were excluded as were patients with liver disease. Serological variables, SLE disease activity index, joint count, and prednisone dose were serially evaluated. Data were analyzed using paired t test and contingency table analysis. RESULTS: Arthritis was the major persistent problem in 7 patients: 1 patient had recurrent pleuropericarditis, 2 patients had refractory cutaneous lupus rashes and 2 had vasculitis. Three patients discontinued MTX because of side effects. The remaining 9 patients have been treated from 7-26 months. In 6 patients the GCS dose was reduced by an average of 42%. In 1 patient symptoms subsided and joint count was reduced without change in the GCS dose. GCS dosage was increased in 2 patients: 1 with recurrent serositis, 1 with persistent vasculitis. No apparent effect on anti-dsDNA antibodies, complement or erythrocyte sedimentation rate (ESR) was noted. CONCLUSION: MTX appears to be useful in selected patients with SLE, especially those with persistent synovitis. PMID- 7799350 TI - Beta 2 glycoprotein I and placental anticoagulant protein I in placentae from patients with antiphospholipid syndrome. AB - OBJECTIVE: To investigate the immunohistological distribution of beta 2 glycoprotein I (beta 2 GPI) and placental anticoagulant protein I (PAP-I) in normal and pathological placentae of patients with antiphospholipid (aPL) antibody associated recurrent fetal loss. These proteins are 2 natural anticoagulants able to interfere with aPL antibody binding. METHODS: Placentae from 4 patients with primary antiphospholipid antibody syndrome (pAPS), from 2 patients with aPL negative systemic lupus erythematosus (SLE) and from 7 healthy women were studied. Cryostatic placental sections were tested by indirect immunofluorescence using polyclonal anti-PAP-I and anti-beta 2GPI antisera as well as purified IgG and anti-beta 2GPI monoclonal antibody. The same tissue sections were also tested by direct immunofluorescence with FITC-F(ab)2 goat antihuman IgG. RESULTS: We found that (a) the placental distribution of PAP-I was comparable in normal and pathological specimens; (b) on the contrary, increased beta 2GPI deposition was present on the trophoblast surfaces of placentae obtained from patients with persistent raised titers of aPL antibodies. Comparable IgG deposition on villi surface was also found in aPL positive but not in control placentae. CONCLUSION: Our data are consistent with the hypothesis that high titer aPL binds to a beta 2GPI phospholipid complex in placentae of women with recurrent fetal loss but that a quantitative deficiency of PAP-I does not play a pathogenetic role in aPL associated fetal loss. PMID- 7799351 TI - Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. AB - OBJECTIVE: To determine the most appropriate clinical measurements for the assessment of ankylosing spondylitis (AS) to develop the new metrology index. METHODS: One hundred and ninety-three individuals with AS were studied. The patients reflected the entire spectrum of cases of AS. Metrology was performed on 327 occasions. First the metrology (20 measurements) of 43 patients was analyzed. From this, 5 simple clinical measurements were defined which most accurately reflect axial status: cervical rotation, tragus to wall distance, lateral flexion, modified Schober's, and intermalleolar distance. These measurements were assessed for reliability, speed and both inter and intraobserver variability in another 40 patients. RESULTS: Analysis of the first group of 43 patients and a subsequent group of 54 patients, using the 5 measurements that constitute this new Bath AS Metrology Index (BASMI), demonstrated that they accurately and reliably mirror the 20 clinical measurements assessed previously (r = 0.92, p < 0.001). In a new group of 40 patients the measurements were demonstrated to be accurate and reproducible for both intraobserver variability (r = 0.99, p < 0.001) and interobserver variability (r = 0.97, p < 0.001). In a further 56 patients, admitted for inpatient therapy, an improvement in the BASMI from 3.34 (SD 2.71) to 2.16 (SD 2.42) was noted over a period of 3 weeks (regardless of disease severity) which indicates a sensitivity to change (chi 2 = 6.55, p < 0.01). The mean improvement over baseline was about 30%. CONCLUSION: Five clinical measurements provide a composite index (BASMI) and define disease status in AS. The BASMI is quick (7 min), reproducible and sensitive to change across the disease spectrum. PMID- 7799352 TI - Olsalazine in ankylosing spondylitis: a pilot study. AB - OBJECTIVE: To test the safety and efficacy of olsalazine in men with ankylosing spondylitis (AS) unresponsive to nonsteroidal antiinflammatory drugs and physiotherapy. METHODS: Four patients, including 2 who had not responded to sulfasalazine (SASP) and one who did not tolerate SASP, were treated with olsalazine, up to 3 g/dl for 24 weeks. RESULTS: One patient discontinued olsalazine due to diarrhea at 1 g/day. The other 3 experienced improvement in global spine self assessment by visual analog scale (VAS), 2 of 3 patients, spinal pain (VAS, 3 of 3), night pain (3 of 3), tender joint count (3 of 3) and enthesis score (3 of 3). Changes in Schober's test and chest expansion were minor. Erythrocyte sedimentation rate and C-reactive protein were normal. Loose stools were the only adverse effects observed. CONCLUSION: Olsalazine appears to be well tolerated and effective in men with AS. Further study of olsalazine and direct comparison with SASP in this population may illuminate mechanisms of drug action and add a new therapeutic option. PMID- 7799354 TI - Protracted febrile myalgia in patients with familial Mediterranean fever. AB - OBJECTIVE: We describe a newly defined syndrome of protracted febrile myalgia in patients with familial Mediterranean fever (FMF). METHODS: Fourteen patients with FMF were admitted with an attack of severe disabling myalgia accompanied by fever, high erythrocyte sedimentation rate, and hyperglobulinemia, lasting up to 6 weeks. RESULTS: Unlike in the classical manifestations of FMF response to corticosteroids therapy was prompt. CONCLUSION: Protracted febrile myalgia is an uncommon dramatic manifestation of FMF that may occur despite colchicine therapy and requires treatment with corticosteroids. PMID- 7799353 TI - The specific antibacterial proliferation of reactive arthritis synovial T cells is not due to their higher proportion of CD45RO+ cells compared to peripheral blood. AB - OBJECTIVE: To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS: The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION: Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA. PMID- 7799355 TI - Tumor necrosis factor-alpha receptor expression on chondrocytes isolated from human articular cartilage. AB - OBJECTIVE: To determine whether the previously observed enhanced susceptibility of osteoarthritic (OA) cartilage to tumor necrosis factor-alpha (TNF-alpha) induced degradation could be due to differences in receptor expression. METHODS: Using specific monoclonal antibodies flow cytometry was used to identify and quantify 2 TNF-alpha receptors on the surface of chondrocytes isolated from human articular cartilage. RESULTS: The proportion of chondrocytes expressing p55 TNF alpha receptor was significantly higher in populations from OA cartilage (p < 0.01) when compared with similar populations from non-arthritic cartilage. The number of p55 receptors/chondrocyte was also significantly higher (p < 0.01) in OA. A significant correlation (r = 0.72, p < 0.18) was found in OA between the numbers of chondrocytes expressing p75 receptor and the number of receptors/chondrocyte. CONCLUSION: p55 TNF-alpha receptor expression is significantly increased on OA chondrocytes ex vivo. Enhanced expression of p55, purported to be the biologically active receptor, could contribute to OA cartilage degradation. PMID- 7799356 TI - Induction of increased levels of proteoglycan fragments in synovial fluid (SF) and increased levels of stromelysin in cartilage, synovium and SF by intraarticular injection of canine monocyte conditioned medium into dogs. AB - OBJECTIVE: To study the effects of the intraarticular injection of canine monocyte conditioned medium (cMCM) into dogs on proteoglycan fragment and stromelysin levels in the joint. METHODS: cMCM was injected intraarticularly into dogs, and the levels of proteoglycan fragments in synovial fluid (SF) as well as stromelysin levels in cartilage, synovium, and SF were assessed after 12 h. RESULTS: There was a 4-fold increase of proteoglycan fragment levels and a 6-fold increase in stromelysin levels in SF, and a 4.4-fold increase in stromelysin levels in cartilage extracts. Elevated mRNA levels were detected in both synovium and cartilage. By immunofluorescence staining, stromelysin was localized in chondrocytes throughout the cartilage and in synovial cells. CONCLUSION: Intraarticular injection of cMCM stimulated the expression of stromelysin mRNA and protein in cartilage and synovium and caused marked increases in stromelysin protein and proteoglycan fragment levels in SF. PMID- 7799357 TI - Growth promoting peptides in osteoarthritis and diffuse idiopathic skeletal hyperostosis--insulin, insulin-like growth factor-I, growth hormone. AB - OBJECTIVE: To investigate growth factors influencing bone and cartilage in patients with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Standard radioimmunoassays (INCSTAR, Stillwater, MN) quantified serum levels of insulin, insulin-like growth factor-I (IGF-I) and growth hormone (GH) in patients with DISH, in patients with osteoarthritis (OA) and in controls. Patients with DISH with comorbidity with obesity, hypertension, diabetes and coronary artery disease, also were studied. RESULTS: Patients with DISH demonstrated normal IGF-I levels; patients with OA had reduced IGF-I levels. Subjects with DISH or OA had elevated insulin and GH values. Patients with DISH with comorbidity had changes in growth factors similar to those found in patients with DISH only. There is frequent association of DISH with obesity, hypertension, coronary artery disease and diabetes mellitus suggesting that these associations are not random. CONCLUSION: Specific associations of skeletal abnormalities with clinical features in which skeletal change and clinical features combine with disturbances of insulin, IGF-I and GH exist in DISH that are distinct from OA. DISH is considered a multisystemic hormonal disorder with protean presentations. PMID- 7799358 TI - Repair characteristics of the articular cartilage surface following acute inflammatory arthritis. AB - OBJECTIVE: To investigate the repair characteristics of the surface protein in an acute arthritis of short duration. METHODS: Knee arthritis in rabbits was induced by intraarticular (ia) injection of 20 micrograms E. coli endotoxin into one knee of 12 rabbits. The contralateral knee served as control. Four animals were killed 3, 6, and 10 days after ia injection. The articular cartilage surface was probed by quantitation of anticollagen type II (anti-CII) antibody binding. The suprapatellar bursae were washed, and the recovered cells counted. RESULTS: A significant increase in anti-CII antibody binding compared to control was measured 3 days after ia injection, coinciding with evidence of acute arthritis (injected joint: 1.1 x 10(7), control: 4.2 x 10(4) cells/joint; percent increase in anti-CII binding: 36.7 +/- 10.7; p < 0.02). Six days after ia injection, the acute arthritis showed a major decrease in intensity whereas anti-CII binding was still abnormal (injected joint: 1.7 x 10(6) cells/joint; percent increase in anti CII binding: 24.7 +/- 19.6; p < 0.05). On Day 10, there was minimal evidence of arthritis in 3 of 4 rabbits, and anti-CII antibody binding returned to normal (injected joint: 1.9 x 10(5) cells/joint; percent anti-CII binding: -5.8 +/- 3.9). There was a strong positive correlation between individual synovial fluid cell counts and the percent increase in anti-CII binding (R = 0.72, p < 0.02). CONCLUSION: The magnitude of binding of anti-CII antibodies to the articular cartilage surface constitutes a sensitive probe for the detection of early damage following a transient inflammatory insult. Our studies indicate that after acute injury, the cartilage surface may show evidence of damage for at least 6 days when probed with anti-CII antibodies. PMID- 7799359 TI - Quantitative microfocal radiographic assessment of osteoarthritis of the knee from weight bearing tunnel and semiflexed standing views. AB - OBJECTIVE: Joint space width (JSW) in osteoarthritis (OA) knee radiography is reported to be optimally assessed from semiflexed standing and tunnel views although no detailed assessment of tunnel view radiography of OA knees has been done. The primary objective of our study was to determine the incidence of joint space narrowing (JSN) in semiflexed standing vs weight bearing tunnel views. The data were also analyzed to examined the degree and relationship of JSN and bony features of OA in the 2 views. METHODS: Ninety OA knees had macroradiographs at 5 times magnification taken in weight bearing standing semiflexed and weight bearing tunnel views. JSW and OA related bony features were measured and compared with reference values obtained from the knees of 14 healthy volunteers without arthritis. RESULTS: Comparison of JSW between the 2 radiographic views identified 3 locations of cartilage loss: JSN recorded in the tunnel only (22%), that in standing view only (8%), and that in both the views (30%). Subchondral sclerosis and osteophytes were significantly larger in 40% of OA knees despite a normal JSW. The tunnel view also enabled better visualization and measurement of osteophytes. CONCLUSION: Standing semiflexed view radiography alone failed to detect JSN in 22% of OA knees. Combined standing and tunnel radiographic views detected JSN more frequently than either view alone. Bony changes were radiographically evident without the presence of JSN indicative of cartilage thinning in as many as 40% of the patients with OA studied. PMID- 7799360 TI - Subclinical renal toxicity in rheumatic patients receiving longterm treatment with nonsteroidal antiinflammatory drugs. AB - OBJECTIVE: To study the possible renal toxicity of longterm treatment with nonsteroidal antiinflammatory drugs (NSAID), in a population of patients with rheumatic diseases. METHODS: Comparative study of 104 patients treated for more than 2 years with NSAID and 123 healthy controls, nonusers of these drugs. After fasting during 12 h the following tests were performed in both groups: urinalysis, creatinine clearance, osmolar clearance, negative free water clearance, and urinary excretion of sodium. RESULTS: In the patient group the urinary pH was higher than in the controls (5.9 +/- 0.7 versus 5.2 +/- 0.6 p < 0.05) and in addition, they had an impaired renal concentration capacity, as it is shown by a significant decreased urinary density (1018.6 +/- 4.7 vs 1026.3 +/- 5.4 in the controls p < 0.05), a decreased urinary osmolality (502.1 +/- 150.7 vs 661.6 +/- 157.6 mOsm/ml p < 0.001), a lower osmolar clearance (1.26 +/- 0.25 ml/min vs 1.83 +/- 0.4 ml/min p < 0.001) and an increased free water clearance ( 0.21 +/- 0.40 ml/min vs -0.98 +/- 0.41 ml/min, p < 0.001). This renal impairment was related to the cumulative intake of NSAID: CONCLUSION: The longterm treatment with NSAID is able to produce a subclinical renal dysfunction, consistent with the early stages of analgesic nephropathy. PMID- 7799362 TI - The challenge of sensorineural hearing loss in rheumatoid arthritis. AB - Patients with rheumatoid arthritis are exposed to a variety of pharmacologic agents capable of causing sensorineural hearing loss. We describe such a patient who was eventually found to have an acoustic neuroma. The case illustrates the difficulty of diagnosing acoustic neuroma and the need for a high index of suspicion when unilateral hearing loss is detected. The evaluation of patients with sensorineural hearing loss is discussed. PMID- 7799361 TI - The reduced expression of glucocorticoid receptors in synovial cells induced by nonsteroidal antiinflammatory drugs can be reversed by prostaglandin E1 analog. AB - OBJECTIVE: We examined the effect of 3 commonly used nonsteroidal antiinflammatory drugs (NSAID), indomethacin, naproxen and tiaprofenic acid, and a prostaglandin E1 analog, misoprostol, on the glucocorticoid receptor level in synovial fibroblasts. METHODS: Synovial fibroblasts were isolated by enzymatic digestion from human normal synovial membranes. These cells were incubated with therapeutic and pharmacological concentrations of NSAID in the presence or absence of misoprostol (0.1-100 ng/ml). The glucocorticoid receptor (GR) level was measured by binding assay using 3H-dexamethasone. RESULTS: Naproxen and indomethacin but not tiaprofenic acid, at therapeutic concentrations, significantly reduced the level of GR in synovial cells. This effect was reversed with the addition of misoprostol. CONCLUSION: Our findings bring insight into the differential effects of NSAID on the GR system and may provide an explanation for the reduced level of GR found in OA chondrocytes. The possible interference with the action of therapeutically administered corticosteroids is discussed. PMID- 7799363 TI - Systemic lupus erythematosus presenting with diffuse low density lesions in the cerebral white matter on computed axial tomography scans: its implication in the pathogenesis of diffuse central nervous system lupus. AB - We describe a patient with systemic lupus erythematosus (SLE) with severe organic brain syndrome, who showed diffuse low density areas in the cerebral white matter on computed axial tomography (CAT) scans. A 43-year-old woman with SLE showed disturbances in various intellectual functions, followed by the development of consciousness disturbances and urinary incontinence. CAT scans, single photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) interleukin 6 (IL-6) were serially examined during the clinical course before and after treatment with high doses of prednisolone. CSF IL-6 activity paralleled the central nervous system (CNS) disease activity most consistently. By contrast, the diffuse low density areas in cerebral white matter on CAT scans as well as the decreased blood flow in the cerebral cortices on SPECT persisted long after the improvement of the CNS manifestations. Magnetic resonance imaging (MRI) scans also revealed the diffuse areas of increased signal intensity in the subcortical white matter on T2 weighted images. The diffuse lesions in the cerebral white matter are considered to reflect the edema as well as other irreversible changes that have resulted from the disturbed cerebral circulation presumably due to the diffuse microangiopathies in the cerebral cortices and not to be necessarily correlated with the CNS disease activities. Moreover, it is suggested that the inflammatory process evidenced by the elevation of CSF cytokines in addition to the disturbed circulation in the cerebral cortices might play an important role in the pathogenesis of CNS lupus in our patient. PMID- 7799364 TI - Combined effects of diltiazem and oxygen in pulmonary hypertension of mixed connective tissue disease. AB - A 45-year-old woman with pulmonary hypertension and mixed connective tissue disease (MCTD) underwent right heart catheterization to evaluate the effects of vasodilators. Nasal oxygen at 2 l/min in addition to 300 mg diltiazem improved pulmonary hemodynamics without adverse effects. After 1 year of diltiazem and home oxygen, sustained favorable hemodynamic effects were obtained, which were more marked than the acute effects. We conclude that this combination may be a potent treatment for pulmonary hypertension in patients with MCTD. PMID- 7799365 TI - Oral metronidazole, an effective treatment for Sweet's syndrome in a patient with associated inflammatory bowel disease. AB - A 39-year-old woman with chronic, recurrent Sweet's syndrome (acute febrile neutrophilic dermatosis) and possible Crohn's disease was successfully treated with oral metronidazole. After 4 years of recurrent skin lesions which involved the hands and face, our patient developed genital and perianal ulcerations which were also histopathologically characterized by a neutrophilic infiltrate. In addition, she had a nondeforming polyarthritis that accompanied recurrences of her skin lesions. The patient was given oral metronidazole, an agent frequently used for perianal Crohn's disease, and achieved complete resolution of the perianal and perineal ulcers, the cutaneous lesions of Sweet's syndrome and the associated polyarthritis. PMID- 7799366 TI - Osteomyelitis subsequent to abdominal-vaginal sacropexy. AB - Vertebral osteomyelitis is an uncommon complication of abdominal-vaginal sacropexy. Our patient developed polymicrobial osteomyelitis postoperatively, with the suspected route of infection attributed to contiguous spread from an infected mesh. PMID- 7799367 TI - Arthritis in a patient with psoriasis after interferon-alpha therapy for chronic hepatitis C. AB - A 27-year-old man with psoriasis was administered with leukocyte derived interferon-alpha for the treatment of chronic persistent hepatitis C. After 3 weeks of injections and eventual normalization of serum levels of alanine aminotransferase, he began to experience polyarthritis, with worsening of psoriatic skin lesions. Tests for antinuclear antibodies and rheumatoid factor were negative, indicating a direct association between interferon therapy and occurrence of seronegative arthritis. PMID- 7799368 TI - Clinical measures in rheumatoid arthritis: which are most useful in assessing patients? PMID- 7799369 TI - Inflammatory myopathy--do we have adequate measures of the treatment response? PMID- 7799370 TI - More on inflammatory myopathy--measures of the treatment response. PMID- 7799371 TI - Disabling fibromyalgia: appearance vs reality. PMID- 7799372 TI - Interrelationship between interleukin 8 and neutrophils in synovial fluid of crystal induced arthritis. PMID- 7799373 TI - Gynecomastia in patients with rheumatoid arthritis treated with methotrexate. PMID- 7799375 TI - Epidemiology and clinical associations of NuMA (nuclear mitotic apparatus protein) autoantibodies. PMID- 7799374 TI - Longterm remission of corneal melting associated with rheumatoid arthritis after a short course of treatment with oral cyclophosphamide. PMID- 7799376 TI - Tidal irrigation in Milwaukee shoulder syndrome. PMID- 7799378 TI - Osteoarticular brucellosis resembling microcrystalline arthropathy. PMID- 7799379 TI - Vth joint World Health Organization and International League of Associations for Rheumatology task force meeting on rheumatic diseases. Geneva, Switzerland, 29 June-2 July 1993. Proceedings. PMID- 7799377 TI - Chondrocalcinosis associated with Bartter's syndrome and hypomagnesemia. PMID- 7799380 TI - DC-ART: improvement and sustained improvement in function. AB - Implementation of the DC-ART category requires a quantitative definition of its descriptive components, the first of which is that such therapy "improve and sustain function." While function is generally taken to include physical, social, and emotional elements, a case is made for restricting function, in this context, to physical function. It is acknowledged that at present there are scanty data on which to determine the minimal size of improvement in function needed to satisfy DC-ART criteria and, in so doing, predict longer term benefit. Until more information is available on predictive data on patients with rheumatoid arthritis and natural course effects in healthy individuals, it is reasonable to use the arbitrary 25-50% improvements traditionally considered by clinicians to represent clinically important change. PMID- 7799382 TI - DC-ART: the concept. AB - The International League of Associations for Rheumatology (ILAR) and the World Health Organization (WHO) have ratified a new classification of antirheumatic therapy comprising two major categories, as follows: (1) Symptom modifying antirheumatic drugs (SMARD) improve the symptoms and clinical features of inflammatory synovitis; (2) Disease controlling antirheumatic therapy (DC-ART) changes the course of rheumatoid arthritis. The DC-ART category, a new group and a new concept, poses a number of problems and challenges but also generates a basis for setting management objectives for rheumatoid arthritis. It is uncertain whether any of the current SMARD would fulfill the stringent DC-ART criteria. PMID- 7799381 TI - DC-ART: decreased inflammatory synovitis. AB - As part of the proposal for drug development using the SMARD/DC-ART definitions, "decreased inflammatory synovitis" needs to be defined. We review the literature with respect to each of the indirect, clinical measures of decreased inflammatory synovitis and recommend a preliminary, testable definition based on a per patient response. It includes minimum disease activity criteria for patients entering studies and improvement in at least 5 of the following 6 criteria: greater than 20% improvement in joint swelling count; greater than 20% improvement in joint tenderness count; greater than 20% improvement in erythrocyte sedimentation rate; greater than 30% improvement in physician/assessor global assessment; greater than 30% improvement in pain. While this definition is sensible within the confines of our knowledge to date, using these criteria prospectively in several clinical trials will allow better definition of the appropriate pooled index to define decreased inflammatory synovitis. PMID- 7799383 TI - DC-ART: preventing or significantly decreasing the rate of progression of structural joint damage. AB - Progressive joint damage, increasing deformity, and declining function characterize rheumatoid arthritis (RA). The evidence suggests structural joint damage is the predominant cause of functional impairment. Structural changes of joints are evaluated by imaging methods. Plain joint radiographs remain the best method for determining the extent and nature of structural changes at present. Newer technologies such as magnetic resonance imaging may eventually replace them. Clinical studies of antirheumatic drugs involving the assessment of prevention or significant decrease in the rate of progression of structural joint damage in RA should meet several standards. All patients who enter a study, whether they continue medication or not, must be assessed on its completion. Studies require sufficient power to determine realistic differences due to therapy. They should last long enough for a reliable analysis of the effects of joint damage; 1 year would be the minimal period for such a study, and 2 years would be preferable. Evaluation should concentrate on erosions and related structural changes in juxtaarticular bone; mapping osteoporotic areas in early disease may be a sensitive and objective measure. Assessments ought to use changes within the hands and wrists to indicate overall progression, with the feet included in evaluating early disease. There should be different therapeutic aims at various stages of RA, focussing on preventing new erosions developing in early disease (< 2 years from diagnosis), preventing new erosions occurring in established disease (2-5 years from diagnosis), reducing the rate erosions develop in established disease (< 5 years from diagnosis), and reducing the rate of joint destruction in late disease (> 5 years from diagnosis). PMID- 7799385 TI - Other special considerations in assessing DC-ART: The need for patient stratification. AB - Given the heterogeneity of rheumatoid arthritis (RA), even in disease of the same duration, it seems likely that some therapeutic regimens will satisfy DC-ART criteria to different degrees in different strata of patients with RA. Since it entails its own problems, it is recommended that the value and feasibility of stratification be evaluated before any attempt to design a DC-ART trial. PMID- 7799384 TI - Are there special considerations relevant to trials of biologic agents? AB - Although biologic agents have been developed to effect change in observed or hypothesized pathogenic pathways, discrepancies between biological and clinical effects are well recognized. In trials of these agents, biological and clinical effects need to be evaluated. While the biological effects require assessment to test the proposed primary effect and significant influences, clinical evaluation should use the same set of assessment procedures as pharmacological agents. The disease controlling antirheumatic therapy (DC-ART) classification with its requirement for longterm efficacy poses problems for the biological agents, which, in general, have demonstrated short term benefit. They may be best accommodated in a new "remission induction" category or, alternatively, as part of longterm combination therapy either with pharmaceuticals or with other biologicals to fulfill DC-ART requirements. PMID- 7799387 TI - DC-ART: what proportion of response constitutes a positive response? AB - In most clinical trials, patients' mean improvement scores are compared either for active against active treatment or active against placebo treatment. Testing drugs or strategies to qualify as disease controlling antirheumatic therapy will require treated patients to satisfy set criteria. But what proportion must fulfill the requirement if the therapy is to be classified as DC-ART? While the answer must address the problems of semantics, disease characteristics, and absolute levels of improvement, it may be easiest to begin by defining a significant degree of change in terms of a single disease activity index. PMID- 7799386 TI - Other special considerations in assessing DC-ART: potential application of newer technologies. AB - Developments in technology will change and improve methods of assessment of rheumatoid arthritis (RA) progress and outcome. Three areas are discussed: quantitative microfocal radiography; assessment of cartilage volume using magnetic resonance imaging and 3D computer reconstruction; polymerase chain reaction on tissue sections to allow simultaneous identification of multiple mRNA for cytokines, leukotrienes, and other participants in RA synovitis in serial blood samples or office-based arthroscopic synovial biopsy sections. PMID- 7799388 TI - Can observational studies replace or complement experiment? AB - The therapeutic effects of interventions in patients with rheumatoid arthritis (RA) are frequently modest. In the assessment of treatments effects, variability due to a variety of sources causes problems that are best controlled by randomized clinical trials. Currently most trials give only a short term picture of RA, a chronic disease whose outcome is multidimensional. Inclusion criteria of clinical trials are frequently very strict, raising concern about the external validity of the results. More longterm data is needed to guide clinical practice. Observational studies may contribute to the body of evidence, but have inherent shortcomings. They are liable to bias and supply weaker evidence. There must be creative development of trial designs suitable for evaluating longterm outcomes. Such trials may include many of the positive features of observational studies, but should not omit the principles of randomization and controlled comparison. PMID- 7799389 TI - Guidelines for testing slow acting drugs in osteoarthritis. AB - New compounds appear to improve symptoms of osteoarthritis (OA), and others are putative chondroprotective agents. We suggest experimental designs for studying the effects of these agents in subjects with hip and knee OA. The course of the articular cartilage lesion is the primary outcome measure to be assessed in putative chondroprotective agent trials. Serial radiographic studies suggest that the annual rate of joint space narrowing in patients with hip or knee OA is about 0.25 mm. Other approaches to quantitation of cartilage loss, e.g., radiographic measurement of the area of joint space, ultrasonography, magnetic resonance imaging and fiberoptic arthroscopy (for knee OA) are under investigation. PMID- 7799390 TI - Intraarticular treatment of osteoarthritis and guidelines to its assessment. AB - Intraarticular treatment has been considered for osteoarthritis since the first attempts at local injection of steroid derivatives. To assess the effectiveness of intraarticular drugs, in view of the variability of the disease and the remarkable placebo response, a control group of patients is necessary. The main outcome measures are pain and joint effusion when using symptomatic slow acting drugs. If a chondroprotective effect is to be demonstrated the main criterion is measurement on standardized radiography of the knee medial femorotibial joint space. PMID- 7799391 TI - Guidelines for use of antirheumatic drugs. AB - The Vth WHO/ILAR Task Force Meeting on Rhemuatic Diseases ratified guidelines for the use of antirheumatic drugs. Indications for use, contraindications, dose, administration and other usage principles, toxicity, and advice to patients have been agreed for analgesics, nonsteroidal antiinflammatory drugs, slower acting antirheumatic drugs, corticosteroids, and hypouricemic agents. PMID- 7799393 TI - Protocol for evaluation of nonsteroidal antiinflammatory drugs. PMID- 7799392 TI - DC-ART classification: review of relevant clinical studies. AB - The proposed disease controlling antirheumatic therapy (DC-ART) definition requires that the therapy change the course of rheumatoid arthritis (RA) for at least 1 year, evidenced by (1) sustained improvement in physical function, (2) decreased inflammatory synovitis, and (3) slowing or prevention of structural joint damage. Selected studies are reviewed. All studies were at least 1 year in duration, but most did not include all 3 of the DC-ART requirements. In these studies, patients treated with placebo generally had no improvement in inflammatory synovitis and progressive structural joint damage, judged by serial joint radiographs. A minority of studies significantly favored one or another of the available agents (gold injections, D-penicillamine, auranofin, antimalarials, azathioprine, sulfasalazine, methotrexate), but the evidence for any one agent is not convincing. For future DC-ART clinical trials patients with early RA should be studied. A hybrid study design may be useful, combining an initial double blind randomized controlled clinical trial with continuing longterm observation of all withdrawals using specified clinical, radiographic, and self report assessments at regular intervals, and an intent-to-treat analysis comparing longterm response rates of the original control and experimental therapy groups. Responsive subgroups should be sought, their characteristics identified, and their responsiveness confirmed in additional trials limited to the identified subgroup. PMID- 7799394 TI - World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. AB - The WHO/ILAR core set of endpoints for rheumatoid arthritis clinical trials signifies progress in a continuing worldwide effort. This core set includes the following measures: pain, patient global assessment, physical disability, swollen joints, tender joints, acute phase reactants, and physician global assessment; in studies of one or more years' duration, radiographs of joints should be performed. PMID- 7799395 TI - N-(acyloxyalkyl)pyridinium salts as soluble prodrugs of a potent platelet activating factor antagonist. AB - Pyrrolothiazole 4 is a potent antagonist of platelet activating factor-mediated effects in a variety of in vitro and in vivo assays. Despite its positive activity in models of inflammation and septic shock, 4 lacks the aqueous solubility necessary for intravenous administration. This deficit was overcome by conversion of 4 to water-soluble pyridinium prodrugs. A two-step procedure was used to prepare a series of N-(acyloxyalkyl)pyridinium salts, all of which exhibited aqueous solubility of greater than 20 mg/mL. The rate of conversion of these prodrugs to 4 was faster in human plasma than in pH 7 aqueous buffer. This rate difference was shown to be due to serum enzymes since the conversion in plasma was significantly slower in the presence of a serine esterase inhibitor. A strong correlation between prodrug structure and buffer/plasma half-life was established. The N-(acetyloxymethyl)pyridinium prodrug 11 (ABT-299) is currently undergoing clinical evaluation for the treatment of sepsis. PMID- 7799396 TI - Ligands for brain cholinergic channel receptors: synthesis and in vitro characterization of novel isoxazoles and isothiazoles as bioisosteric replacements for the pyridine ring in nicotine. AB - Ligands which activate neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential approach for the palliative treatment for the symptoms of memory loss associated with Alzheimer's disease (AD). Based upon this approach, a series of novel 3,5-disubstituted isoxazoles and isothiazoles were prepared and evaluated in vitro as cholinergic channel activators (ChCAs) of neuronal nAChRs. Many of the 3-substituted 5-(2-pyrrolidinyl)isoxazoles were found to have nanomolar binding affinities comparable to (S)-nicotine (2a) in a preparation of whole rat brain. However, in a paradigm measuring the evoked release of [3H]dopamine from a preparation of rat striatum, there were differences in the agonist potencies and efficacies of these analogues relative to 2a. The differences in agonist potency observed between compounds of comparable binding potency may be due to differences in ligand interactions with various subtypes of neuronal nAChRs. PMID- 7799397 TI - Triazolinone biphenylsulfonamides as angiotensin II receptor antagonists with high affinity for both the AT1 and AT2 subtypes. AB - Angiotensin II (AII), the endogenous peptide ligand of the AII receptor, has equivalent high affinity for both the AT1 and AT2 receptor subtypes while most of the reported nonpeptide AII antagonists are AT1-selective. In an effort to identify dual AT1/AT2 nonpeptide AII antagonists, we have pursued modifications of previously prepared trisubstituted 1,2,4-triazolinone biphenylsulfonamides which exhibited subnanomolar in vitro AT1 (rabbit aorta) AII antagonism and AT2 (rat midbrain) IC50 values of < 40 nM. Present results show that a suitable amide (or reversed amide) side chain appropriately positioned on the N2-aryl group of these compounds gave > 15-fold enhancement in AT2 binding affinity without sacrificing nanomolar AT1 potency (IC50). This added amide, combined with an appropriate choice of the N-substituent on the sulfonamide and the ortho substituent on the N2-aryl group, led to an analogue (46, L-163,-007) which exhibited subnanomolar AT1 binding affinity and an AT2/AT1 IC50 ratio of 3. This compound showed excellent iv activity at 1 mg/kg and oral efficacy at 3 mg/kg with > 6 h duration in a conscious rat model. Available data suggest that the newly introduced amide side chain, mandatory for low nanomolar binding affinity at the AT2 receptor, is well-tolerated by the AT1 receptor and has minimal effect on the in vivo properties of these molecules. PMID- 7799398 TI - The discovery of novel, structurally diverse protein kinase C agonists through computer 3D-database pharmacophore search. Molecular modeling studies. AB - A computer protein kinase C (PK-C) pharmacophore search on 206,876 nonproprietary structures in the NCI 3D-database led to the discovery of five compounds which were found to possess PK-C binding affinities in the low micromolar range and six others having detectable, but marginal, binding affinities. Molecular modeling studies showed that in addition to the presence of the defined pharmacophore, hydrophobicity and conformational energy are the two other important factors determining the PK-C binding affinity of a compound. The modeling results were confirmed by synthetic modification of two inactive compounds, producing two active derivatives. These newly discovered, structurally diverse lead compounds are being used as the basis for further synthetic modifications aimed at more potent PK-C ligands that will compete with the phorbol esters. PMID- 7799399 TI - kappa Opioid receptor selective affinity labels: electrophilic benzeneacetamides as kappa-selective opioid antagonists. AB - 2-(3,4-Dichlorophenyl)-N-methyl-N-[1-(3- or 4-substituted phenyl)-2-(1 pyrrolidinyl)ethyl]-acetamides 3-6 were synthesized as kappa-selective affinity labels and evaluated for opioid activity. In smooth muscle preparations, the non electrophilic parent compound (+)-S-2 and the affinity labels 3-6 behaved as kappa agonists in that they were potently antagonized by norbinaltorphimine (norBNI). In addition to the high binding affinity and selectivity of the 3 isothiocyanate 3 (DIPPA) to kappa opioid receptors, wash studies have suggested that this involves covalent binding. In the mouse tail-flick assay, the 3- and 4 substituted isomers (3 and 5, respectively) produced long-lasting antagonism of the antinociceptive effect of the kappa opioid agonist, (+/-)-trans-2-(3,4 dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]acetamide ((+/-) U50,488). In contrast, the non-electrophilic parent compound (+)-S-2 and the fumaramate derivative 4 were devoid of antagonist activity in the tail-flick assay. At substantially different doses, DIPPA (3) and the 4-isothiocyanate 5 also produced antinociception in the mouse abdominal stretch assay. In addition, DIPPA and the 3-fumaramate methyl ester 4 had improved in vivo kappa selectivities compared to the unsubstituted parent compound (+)-S-2 and the para substituted derivative 5. The improved kappa-selectivities of 3 and 4 and the different agonist and antagonist potencies of 3 and 5 may be explained respectively by the existence of multiple kappa agonist binding sites and distinct agonist and antagonist binding sites. In view of the antagonist selectivity and the apparent irreversible binding of DIPPA to kappa receptors, it may serve as a useful pharmacologic or biochemical tool to investigate kappa opioid receptors. PMID- 7799400 TI - A conformationally defined 6-s-trans-retinoic acid isomer: synthesis, chemopreventive activity, and toxicity. AB - A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z configuration for the intermediate aldehyde. A Horners-Emmons condensation with this aldehyde then produced retinoic acid analogs with both 9Z- and 9Z,13Z configurations. An I2-catalyzed isomerization of the intermediate 9Z-aldehyde yielded the all-E-aldehyde, which was olefinated as above to yield the (all-E)- and (13Z)-retinoic acid analogs of 1. Each configurational isomer of 1 was evaluated for its ability to inhibit the binding of retinoic acid to CRABP (chick skin) and to inhibit the chemical induction of ornithine decarboxylase in mouse skin. In each assay (all-E)-1 was the most active isomer, and this activity was comparable to or better than that for (all-E)-retinoic acid. (all-E)-1 and (13Z) 1 were both shown to be equally effective as (13Z)-retinoic acid in suppressing the proliferation of human sebaceous cells in vitro. (all-E)-1 was further evaluated for its ability to prevent the induction of mouse skin papillomas and to induce signs of vitamin A toxicity in mice. The cancer chemopreventive activity of (all-E)-1 was comparable to that of (all-E)-retinoic acid, and the toxicity was comparable to or slightly better than that of the natural vitamin. PMID- 7799401 TI - Structural evolution and pharmacology of a novel series of triacid angiotensin II receptor antagonists. AB - cis-4-(4-Phenoxy)-1-[1-oxo-2(R)-[4-[(2-sulfobenzoyl)amino)-1H- imidazol-1 yl]octyl]-L-proline derivatives represent a novel class of potent nonpeptide angiotensin II (Ang II) receptor antagonists. These compounds evolved from directed structure-activity relationship (SAR) studies on a lead identified by random screening. Further SAR studies revealed that acidic modification of the 4 phenoxy ring system produced a series of triacid derivatives possessing oral activity in pithed rats. The most potent compound, cis-4-[4 (phosphonomethyl)phenoxy]-1-[1-oxo-2(R)-[4-[(2-sulfobenzoyl+ ++) amino]-1H imidazol-1-yl]octyl]-L-proline (1e), inhibited the pressor response to exogenously administered Ang II for periods up to 8 h following oral dosing. The antihypertensive activity of 1e was evaluated in the Lasix-pretreated conscious spontaneously hypertensive rat (SHR) where it produced a dose-dependent fall in blood pressure following oral dosing lasting > 12 h. Antagonists such as 1e may serve as useful therapeutic agents for the treatment of hypertension as well as for studying the role of Ang II in various disease states. PMID- 7799402 TI - 2,4-Diamino-5-chloroquinazoline analogues of trimetrexate and piritrexim: synthesis and antifolate activity. AB - Ten heretofore undescribed 2,4-diamino-5-chloroquinazoline analogues of trimetrexate (TMQ) and piritrexim (PTX) were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) from rat liver, Pneumocystis carinii, and Toxoplasma gondii. The most active quinazolines against both the P. carinii and the T. gondii enzyme were those with an ArCH2-NH or ArNHCH2 side chain. Among ArNH(CH2)n compounds with n = 1-3 and either 2',5'-dimethoxyphenyl or 3',4',5' trimethoxyphenyl as the Ar moiety, activity decreased in the order n = 1 > n = 2 > n = 3. The best inhibitor of P. carinii DHFR, 2,4-diamino-5-chloro-6-[(N-methyl 3',4',5'-trimethoxyanilino)methy l] quinazoline (10) had an IC50 of 0.012 microM and was slightly more potent than TMQ and PTX. Compound 10 was also the best inhibitor of T. gondii DHFR, with an IC50 of 0.0064 microM corresponding again to a minor increase in activity over TMQ and PTX. However, as with these standard agents, 10 showed no appreciable selectivity for either the P. carinii or T. gondii enzyme relative to the rat liver enzyme. The highest selectivity achieved in this limited series was with 2,4-diamino-5-chloro-6-[N-(3',4',5' trimethoxybenzyl)-N-methylamino] quinazoline (17) against T. gondii DHFR. While 17 (IC50 = 0.016 microM) was somewhat less potent than 10, its selectivity, as defined by the ratio IC50(rat liver)/IC50(T. gondii) was ca. 30-fold higher than that of TMQ or PTX. Two compounds, 2,4-diamino-5-chloro-6-[(3',4',5' trimethoxyanilino)methyl] quinazoline (9) and 2,4-diamino-5-chloro-6-[N-(3',4',5' trimethoxybenzyl) amino]quinazoline (15), were also tested against human DHFR and were found to have an IC50/[E] of 0.5, indicating that their binding was near stoichiometric. PMID- 7799403 TI - Structure of a covalent DNA minor groove adduct with a pyrrolobenzodiazepine dimer: evidence for sequence-specific interstrand cross-linking. AB - The structure of the interstrand cross-linked adduct formed between a C8-C8' linked pyrrolobenzodiazepine (PBD) dimer (DSB-120; 1,1'-(propane-1,3 diyldioxy)bis[(11aS)-7-methoxy-1,2,3,11a-t etrahydro-5H- pyrrolo[2,1 c][1,4]benzodiazepin-5-one]) and a self-complementary d(CICGATCICG)2 duplex has been determined from high-field 1D- and 2D-NMR data using a simulated annealing procedure. The refined structure supports earlier observations from solution NMR experiments and indicates that the covalently bound molecule spans six DNA base pairs in the minor groove, forming a symmetric cross-link between the spatially separated internal guanines and with active recognition of an embedded 5'-GATC bonding site. This result confirms that template-directed approaches are useful for the design of linked DNA-interactive PBD dimers with viable DNA cross-linking potential. Further, head-to-head connection of the PBD moieties results in an overall retention of 5'-GA bonding site preference for each alkylating PBD subunit. Structural analysis indicates that cross-link formation results in a localized perturbation of the DNA duplex, attributable in part to a mutual reduction in dynamic mobility or "covalent clamping" within the Gua4-Cyt7 base tract. However, ligand-induced distortion is confined to the Cyt7 and Ino8 residues on each strand. The Gua(N2)-Gua(N2) cross-link is stabilized by two directed H-bonds from the formed animal residues to N3 acceptor atoms of adenine bases on the 3'-side of each covalently modified guanine. Evidence for sequence specific cross-linking with DSB-120 is provided by extended modeling studies which suggest that recognition of the favored d(.GATC.) motif is dominated by van der Waals steric factors, although electrostatic and H-bonded interaction terms also play a key role. This conclusion supports recent covalent footprinting studies revealing that this PBD dimer shows a selectivity for embedded base sequences of the type 5'-(pu/py)GATC(py/pu). PMID- 7799404 TI - Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones. AB - Valylprolyvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lung hemorrhage models. The compound with 4-(4 morpholinylcarbonyl)benzoyl as the protecting group, 71 (MDL 101,146), was studied in greater detail. Hydration and epimerization studies were performed on 71 and related compounds in various media, including human blood serum. High performance liquid chromatography studies on a reversed-phase system as a measure of the lipophilicity of 71 and related compounds revealed a small range of relative retention times wherein the orally active compounds fell. The Ki value determined for 71 vs HNE was 25 nM. PMID- 7799405 TI - Pentamidine congeners. 2. 2-butene-bridged aromatic diamidines and diimidazolines as potential anti-Pneumocystis carinii pneumonia agents. AB - We have synthesized cis and trans geometric isomers 1-8 as semirigid congeners of pentamidine. Compounds 1-4 were more potent than pentamidine in treating Pneumocystis carinii pneumonia in immunosuppressed rats. These compounds also demonstrated no clinical toxicity or histopathologic abnormalities. Introduction of methoxy substituents meta to the amidine or imidazoline groups of the phenyl rings as in compounds 5-8 generally resulted in compounds with decreased anti-P. carinii activity and increased toxicity to the host. Compounds 1-4 were evaluated as DNA binders. These compounds showed greater affinity for poly(dA).poly(dT) than for calf thymus DNA. The cis isomers, 1 and 2, demonstrated greater affinity for DNA than their trans counterparts 3 and 4. This difference in DNA binding affinity, however, did not reflect in a corresponding difference in the anti-P. carinii activity of these compounds. PMID- 7799406 TI - A bioactive fullerene peptide. AB - The highly hydrophobic C60 (buckminsterfullerene) was water solubilized by covalently linking the synthon 1,2-dihydro-1,2-methanofullerene [60]-61 carboxylic acid to the alpha-amino group of the hydrophilic 4-8 sequence of peptide T, known to display potent human monocyte chemotaxis. The resulting compound, characterized by a variety of analytical techniques, including a UV spectrum in aqueous solution, exhibits remarkable chemotactic potency, comparable to that of the parent pentapeptide. Furthermore, this fullerene-peptide conjugate inhibits, albeit weakly, HIV-1 protease. PMID- 7799407 TI - A novel and useful descriptor for hydrophobicity, partition coefficient micellar water, and its application to a QSAR study of antiplatelet agents. AB - Herein we describe the introduction and application of a novel and useful descriptor, logarithm of micelle-water partition coefficients (log Pmw), for hydrophobicity of compounds. A QSAR study using log Pmw on antiplatelet activities ex vivo of 2-substituted phenyl and benzimidazolyl-5-methyl-4-(3 pyridyl)imidazoles showed its usefulness. Antiplatelet activities could be rationalized by means of only log Pmw with an excellent correlation (r = 0.772, s = 0.257, F = 11.07 **, n = 18), while use of other descriptors such as CLOGP values and retention factors (k') failed. Pmw values can easily be obtained using a normal HPLC system using a micelle aqueous solution as the mobile phase. HPLC techniques offer the advantage of tolerating lower sample purity, smaller sample size, and being dynamic range, compared with the flask-shaking method for measurement of logarithm of 1-octanol/water partition coefficients (log P), which is widely used in QSAR study. These indicated that log Pmw could be a useful descriptor for hydrophobicity of compounds. PMID- 7799409 TI - Derivatives of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl-p iodobenzamido)ethyl]pipera zine (p-MPPI) as 5-HT1A ligands. AB - A series of new p-alkylbenzamido derivatives of 4-(2'-methoxyphenyl)-1-[2'-(N-2" pyridinyl)-p- iodobenzamido)ethyl]piperazines (p-MPPI) were prepared. In vitro binding studies suggest that p-methyl and p-ethyl substituents on the benzamido group display the same high binding affinity to 5-HT1A receptors (Ki = 2.2 and 9.3 nM, rat hippocampal homogenates). However, when the substitution groups were larger than a C5 pentyl group, the affinity to 5-HT1A receptors dropped below a useful level (Ki > 50 nM). Several irreversible binding agents (CH2Cl, NHCOCH2Cl) and a photoaffinity labeling compound (m-iodo p-azido) which showed good binding affinity to 5-HT1A receptors were successfully prepared. PMID- 7799410 TI - Four amino acid exchanges convert a diazepam-insensitive, inverse agonist preferring GABAA receptor into a diazepam-preferring GABAA receptor. AB - Benzodiazepines (BZ) exert their effects through GABAA receptors, which belong to the superfamily of ligand-gated ion channels. Coexpression of recombinant alpha, beta, and gamma subunits in a cell culture system mimics the BZ binding sites. The alpha variants largely determine the nature of the BZ binding site in such alpha i beta j gamma k heteromultimers (i = 1-6; j = 1-3; k = 1-3). Notably, the alpha 1 and alpha 6 variants confer high and low affinity for BZ agonists to the resulting receptor subtype, respectively. Glycine/glutamate and histidine/arginine positions in the alpha subunits of alpha x beta 2 gamma 2 receptors are involved in BZ I versus BZ II type selectivity. We now identify four amino acids in alpha 6 which together increase the affinity of the mutant alpha x beta 2 gamma 2 receptor for classical BZ receptor agonists above the level seen for any wild-type GABAA/BZ receptor. The most pronounced effect was due to an isoleucine to valine exchange. It simultaneously decreased the affinity for the BZ partial inverse agonist Ro 15-4513 20-fold and increased the affinity for diazepam 4-fold. The four amino acid residues stretch over most part of the N terminal extracellular domain of the alpha subunit, suggesting that amino acids distant in the primary sequence form the BZ binding pocket. PMID- 7799408 TI - Synthesis and anticonvulsant activities of alpha-acetamido-N-benzylacetamide derivatives containing an electron-deficient alpha-heteroaromatic substituent. AB - Recent studies have demonstrated that C(alpha)-substituted alpha-acetamido-N benzylacetamides displayed excellent anticonvulsant activities in mice. Analysis of the structure-activity relationship for this series of compounds has shown that placement of small, electron-rich aromatic and heteroaromatic groups at the C(alpha) site led to pronounced protection against MES-induced seizures. In this note, synthetic protocols are reported for the preparation of three novel nonnaturally occurring electron-deficient C(alpha)-aza aromatic alpha-acetamido-N benzylacetamides (i.e., pyrid-2-yl (11), pyrazin-2-yl (12), pyrimid-2-yl (13)). Expedient syntheses for 12 and 13 were developed using a phase-transfer, nucleophilic aromatic substitution process. All three adducts exhibited potencies comparable to or greater than phenytoin in the MES test (mice, ip). These findings required us to modify in part the previously proposed structure-activity relationship for this class of anticonvulsants. PMID- 7799411 TI - [Detection of Helicobacter pylori by the urease test in 244 patients]. AB - The authors report the results of the detection of Helicobacter Pylori (HP) in gastric mucosa by the urease test, in 244 patients between January 1989 and August 1991. The overall prevalence of HP was 38.1%. It was 19.5% in patients with normal upper gastrointestinal endoscopy (UE), 61% in duodenal ulcer (p < 0.001) and 68.7% in congestive antritis (p < 0.001), significantly higher than in controls. There was no significant difference between controls and patients with erosive antritis or healed duodenal ulcers. The prevalence of HP rises with age in all patients and in those with lesions at UE but not in those with normal UE. A rise of this prevalence seems to exist in the months of June and December. The authors conclude by pointing out the rise of the overall prevalence of HP in congestive antritis compared with erosive antritis, the similarity of prevalence in normal subjects and those with healed ulcer and the lack of influence of age on this prevalence in subjects with normal UE. These conclusions are in need of confirmation by further studies on much more longer series. PMID- 7799412 TI - [Diagnosis of recurrent bronchopulmonary infections in children]. AB - One hundred and seven patients aged from nine months to eight years old have been studied to evaluate the diagnosis of broncho-pulmonary recurrent infection with a preliminary studies and an association of bronchoscopy and bronchography. The first step cheek-in revealed sixty-seven diagnosis, while the bronchoscopy, the bronchography and the IgG subclasses revealed respectively twenty-seven, five and three diagnoses. Only five patients remained without diagnosis. PMID- 7799414 TI - [Dyslipidemia: what every physician should keep in mind]. PMID- 7799413 TI - The dysplastic melanocytic nevus: a helping hand in the prevention of malignant melanoma. PMID- 7799415 TI - Continuing medical education: the American approach. PMID- 7799416 TI - [Health situation in the world]. PMID- 7799417 TI - Weight control in the management of hypertension. World Hypertension League. AB - This article, which includes a brief description of the mechanisms and some epidemiological findings in obesity and high blood pressure, sums up present knowledge on a complex subject and provides guidance to medical practitioners on the management of obese hypertensive patients. Weight reduction, together with drug therapy in severe and moderate hypertension, and other non-pharmacological methods and continuing observation in mild hypertension are the essential measures to be applied. In addition to the lowering of blood pressure, weight loss offers several other metabolic and haemodynamic benefits. PMID- 7799421 TI - Juvenile reflex sympathetic dystrophy: a case report. AB - We report a case of reflex sympathetic dystrophy in a 10-year-old girl who presented with a two months history of severe pain and paresthesia in her right lower extremity. The patient made a very good recovery after two months of treatment with steroids and physical therapy. PMID- 7799422 TI - [Ethics of pain in terminal stage: to inform, to care and to relieve the suffering]. PMID- 7799418 TI - [Incidentally discovered adrenal tumor: myelolipoma]. AB - The wider application of increasingly sensitive ultrasonography and CT scanning has created a new problem for clinical management: the incidental discovery of asymptomatic adrenal lesions. These lesions, also called "incidentalomas" may be due to a large variety of etiologies, and although most of them prove to be benign cortical adenomas, diagnostic confirmation is frequently impossible preoperatively. For this reason, a general approach, based on the relative prevalence of benign and malignant, clinically silent adrenal masses, has been defined. This same approach is usually needed in the case of myelolipoma, a rare form of benign and silent adrenal neoplasms, containing hematopoietic and fatty elements. Actually, computed tomographic aspect of such tumors is very evocative but not pathognomonic, so it doesn't eliminate the possibility of malignant lesions, especially in the presence of heterogeneities. Because of these limitations and awaiting the development of more specific diagnostic procedures, it seems cautious to approach these tumors like incidentalomas in general. PMID- 7799419 TI - Traumatic rupture of the thoracic aorta--case report. AB - Acute traumatic rupture of the thoracic aorta due to blunt trauma is a relatively common injury after deceleration accidents. However, only one fifth of these patients survive to reach medical facilities. The limiting factor to successful management is early diagnosis and prompt treatment. A case of acute traumatic rupture of the descending aorta due to blunt trauma is presented. Diagnostic and management modalities are discussed. PMID- 7799420 TI - [A case of trichinosis revealed by a protracted diarrhea and neurologic manifestations]. AB - We report a case of trichinosis presenting with a subacute persistent diarrhea and neurologic complications. Gastrointestinal endoscopic as well as digestive and neurologic radiologic signs were observed. The mainstay of treatment was glucocorticoids associated with thiabendazole. The patient responded well to this regimen. A literature review to explain the gastrointestinal and neurological manifestations of trichinosis as well as their management was done. PMID- 7799423 TI - Cancer pain: pharmacological management (2). PMID- 7799424 TI - The measurement of intracellular antigens and DNA by multiparametric flow cytometry. AB - The aim of this paper is to provide a strategy for measuring intracellular antigens combined with DNA content in cells or nuclei. A series of protocols are included which enable the majority of such antigens to be labelled and further information is provided for cases in which the standard methods prove to be inadequate. The basic principles of cell permeabilization/fixation are described, thus explaining how methods can be divided into three basic categories: (a) alcohol fixation with or without detergent pretreatment; (b) paraformaldehyde fixation followed by permeabilization with alcohol or detergents; (c) permeabilization of unfixed cells. The preparation of nuclear suspensions from paraffin-embedded material is described and the possibilities and problems of staining such suspensions for nuclear antigens are discussed. Examples of results obtained with the detailed protocols are given for staining with antibodies directed against proliferating cell nuclear antigen (PCNA), Ki-67 antigen and Ki S1 antigen. Details of published studies of a variety of intracellular antigens are given in two tables. The power of multiparametric flow cytometry in the study of cell proliferation, differentiation and response of cells to damage is underlined. PMID- 7799425 TI - Rapid assay for pathogenic Salmonella organisms by immunofluorescence flow cytometry. AB - Multi-parameter flow cytometry was investigated for the rapid detection of specific serotypes of salmonellas (S. typhimurium and S. montevideo) labelled with fluorescent monoclonal antibodies, both in pure culture and in a typical food matrix (full-fat milk). In all cases, the method was accurate to levels of below 10(4) target cells per ml for a total assay time of about 30 min. After 6 h non-selective enrichment in the presence of a 10,000-fold excess of competing micro-organisms (Escherichia coli) the corresponding detection limit was about 20 cells ml-1. These results suggest that flow cytometry has significant potential for the detection of pathogenic micro-organisms in the food industry. PMID- 7799426 TI - Scanning microphotolysis: a new photobleaching technique based on fast intensity modulation of a scanned laser beam and confocal imaging. AB - The fluorescence photobleaching method has been widely used to study molecular transport in single living cells and other microsystems while confocal microscopy has opened new avenues to high-resolution, three-dimensional imaging. A new technique, scanning microphotolysis (Scamp), combines the potential of photobleaching, beam scanning and confocal imaging. A confocal scanning laser microscope was equipped with a sufficiently powerful laser and a novel device, the 'Scamper'. This consisted essentially of a filter changer, an acousto-optical modulator (AOM) and a computer. The computer was programmed to activate the AOM during scanning according to a freely defined image mask. As a result, almost any desired pattern could be bleached ('written') into fluorescent samples at high definition and then imaged ('read') at non-bleaching conditions, employing full confocal resolution. Furthermore, molecular transport could be followed by imaging the dissipation of bleach patterns. Experiments with living cells concerning dynamic processes in cytoskeletal filaments and the lateral mobility of membrane lipids suggest a wide range of potential biological applications. Thus, Scamp offers new possibilities for the optical manipulation and analysis of both technical and biological microsystems. PMID- 7799427 TI - Direct imaging in a water layer of human chromosome fibres composed of nucleosomes and their higher-order structures by laser-plasma X-ray contact microscopy. AB - X-ray contact microscopy with a 300-ps-duration laser-plasma X-ray source has been used to image hydrated human chromosomes. Clearly imaged are individual nucleosomes and their higher-order particles (superbeads), elementary chromatin fibrils. c. 30 nm in diameter and their higher-order fibres of various sizes up to c. 120 nm in diameter. The results demonstrate that X-ray microscopy is now capable of opening a new path of investigation into the detailed structures of hydrated chromosome fibres in their natural state. PMID- 7799428 TI - Relocation accuracy on HOME computerized microscopes. AB - A major practical advantage of the HOME (highly optimized microscope environment) computerized microscope is the facility for relocating cells or other microscopic objects. Features can be marked directly on the microscope image using a mouse driven cursor, and an interactive finder can then be used to relocate the marked features. Tests on a prototype HOME microscope have shown that positions can be relocated with an accuracy of standard deviation (SD) < 7 microm. The marked features could also be relocated on a second HOME microscope, although with somewhat reduced accuracy (standard deviations of < 17 microm). The system provides a very user-friendly environment for tasks requiring relocation of microscopic objects. PMID- 7799430 TI - Order-disorder phenomena in myelinated nerve sheaths: V. Effects of temperature on rat sciatic and optic nerves, and structural differences between the two types of nerve. AB - We describe in this work X-ray scattering and electron microscope studies of rat sciatic and optic nerves as a function of temperature. The scattering experiments were analyzed as described in the previous papers of this series: a variety of parameters were determined, some of which characterize the lattice disorder, others the structure of the motif. The main results are the following. All the parameters determined by the X-ray scattering study vary with temperature and the temperature-dependence is specific for the type of nerve (sciatic or optic). Most of the disorder-related parameters display a minimum or a maximum in the vicinity of physiological temperature (38 degrees C in rat); this observation, strongly supported by the electron microscope study, shows that the degree of organization of myelin is highest near physiological temperature. The structure of the motif, as revealed by the electron density profile, is fairly different in the two types of nerves (in contrast with the assumption made by previous workers); the structure also varies with temperature and the temperature-induced alterations are nerve-type specific. In the two types of nerve the thickness of the lipid bilayer varies with temperature as expected for a lipid-containing system with hydrocarbon chains in the disordered conformation. In sciatic nerve the thickness of the (thinner) cytoplasmic polar layer, which is also the layer most affected by lattice disorder in this type of nerve, decreases dramatically with increasing temperature. In optic nerve, in which lattice disorder predominantly affects the extracellular layer, the thickness of both the cytoplasmic and the extracellular layer is barely affected by temperature. PMID- 7799431 TI - Mutational analysis of the prohead binding domain of the large subunit of terminase, the bacteriophage lambda DNA packaging enzyme. AB - Terminase, the DNA packaging enzyme of bacteriophage lambda, is made up of two subunits, gpNul and gpA, the products of the Nu1 and A genes. The activities of terminase include DNA binding, cos cleavage and prohead binding. Specificity domains within the structure of terminase have previously been defined by genetic studies of lambda-21 hybrids. The prohead binding domain of terminase is localized to the last 32 amino acid residues of gpA. Mutations in the prohead binding domain of gpA were constructed by introducing the corresponding amino acids from gp2, the gpA analog of bacteriophage 21. The last five residues of gpA can be replaced with little effect on the burst size of lambda. A phage with a replacement of the last six residues of gpA with the corresponding residues of gp2 was unable to form plaques, indicating that the sixth-to-last residues of gpA is crucial for prohead binding. Site-specific mutagenesis of the sixth-to-last position of gpA indicated that the sixth-to-last residue of gpA must be hydrophobic, of the seven amino acids tested, only isoleucine and valine can substitute for leucine at this position. Although the last five residues of gp2 were functional when they replaced the last five residues of gpA, two results indicated that the last five residues of gpA functioned better than the corresponding residues of gp2. First, the presence of a valine residue at the sixth-to-last position of gpA allowed plaque formation, whereas replacement of the last six residues of gpA with those of gp2, which substitutes a valine residue at the sixth-to-last position, was lethal. The second set of results indicating that the last five residues of gpA function better than the gp2 residues were obtained by study of revertants of lethal substitution mutations. In constructing the replacement mutations, a short linker was inserted into the C terminus of the A gene; this insertion created a short duplication of the end of the A gene, so that the normal C-terminal codons were located downstream of the stop codon of the A gene in the substitution mutants. Revertants of the lethal substitution mutations were obtained in which a mutation in the stop codon resulted in addition of the last five residues of gpA to the end of the substitution terminase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7799429 TI - Rapid estimation of bacterial antibiotic susceptibility with flow cytometry. AB - Bacterial antibiotic susceptibility was rapidly estimated for Escherichia coli and Staphylococcus spp. by flow cytometry. This was achieved by measuring the uptake of a negatively charged membrane potential sensitive dye bis-(1,3-dibutyl barbituric acid) trimethine oxonol and observing changes in low-angle light scatter (excitation light scattered by up to 15 degrees). Estimations of ampicillin, gentamicin and ciprofloxacin susceptibilities were possible within 2 5 h from a plate culture, depending on the species and antibiotic used. This includes the time necessary to establish steady-state growth in liquid culture. PMID- 7799432 TI - Specific interaction of terminase, the DNA packaging enzyme of bacteriophage lambda, with the portal protein of the prohead. AB - Terminase, the bacteriophage lambda DNA packaging protein, is a heteromultimer of two subunits, gpNu1 and gpA, the products of genes Nu1 and A, resp. Phage 21 is a lambdoid phage that produces a terminase similar to that of lambda terminase, the subunits of 21 terminase, gp1 and gp2, have the same domain structures of their lambda analog, gpNu1 and gpA, respectively. The lambda and 21 terminases have different DNA binding and prohead binding specificities. When the C-terminal 32 amino residues of gpA replace the C-terminal 32 residues of gp2, the resulting chimeric terminase specifically uses lambda proheads, indicating that the C terminal 32 residues of gpA are a specificity domain for prohead binding. A second chimeric terminase, in which the C-terminal six residues of gpA are replaced by the C-terminal six residues of gp2, is unable to utilize lambda proheads, and a lambda phage producing this terminase, lambda Are636, is unable to form plaques. In the present work, a pseudorevertant of lambda Are636 was isolated that contained a mutation Bms8, affecting the prohead. The B gene encodes the portal protein of lambda proheads, which forms the special vertex that is thought to serve as (1) the site of DNA entry into the prohead during packaging, (2) the site for DNA exit during DNA injection, and (3) the site of tail attachment during virion assembly. Bms8 is predicted to change residue 331 of gpB from proline to serine. Burst size measurements and in vitro DNA packaging experiments demonstrated allele-specific interactions between the Are636 terminase and Bms8 proheads. That is, wild-type terminase interacted more efficiently with wild-type proheads than with Bms8 proheads, and Are636 terminase interacted with Bms8 proheads more efficiently than with wild-type proheads. Prohead binding by lambda terminase is stimulated by an assembly catalyst, gpFI. In vitro packaging extracts lacking gpFI were used under conditions in which packaging was gpFI-independent. In the absence of gpFI, Are636 terminase interacted most efficiently with Bms8 proheads, and wild-type terminase interacted most efficiently with wild-type proheads. The allele-specific interactions in the absence of gpFI indicate that the Are636 and Bms8 mutations affect direct interactions between terminase and the portal protein, rather than acting indirectly by altering the interactions of terminase and gpB and gpFI. PMID- 7799434 TI - Trifluoroethanol-induced stabilization of the alpha-helical structure of beta lactoglobulin: implication for non-hierarchical protein folding. AB - Trifluoroethanol (TFE) is known to stabilize the alpha-helical structure in proteins and their fragments. However, the relationship between the TFE-induced structures and the native structure is not clear. Here we show that beta lactoglobulin, which consists predominantly of beta-sheets, exhibited a markedly high propensity to form an alpha-helical structure in the presence of TFE, as measured by far-UV circular dichroism. A cooperative transformation from the beta sheet structure to an alpha-helical structure occurred at a TFE concentration between 10% and 20%. These results were in contrast to a gradual beta-sheet to alpha-helix transition of the constant fragment of the immunoglobulin light chain, which is also a beta-sheet protein. To understand the significance of the high helical propensity of beta-lactoglobulin, we measured the TFE-induced conformational transition of more than 20 proteins of various secondary structural types. Whereas the alpha-helical proteins showed a propensity to form an extensive helical structure in TFE, the helical propensity of proteins with a low helical content in the native state varied. The helical content in TFE was correlated more with the helical content predicted by a secondary structure prediction than with the helical content of the native structure, suggesting that the stability of the helical structure in TFE is determined by local interactions between nearby amino acid residues. Our results suggest that an alpha-helical intermediate can accumulate during the refolding process of beta-lactoglobulin and that a hierarchical model of protein folding is not necessarily true for some beta-sheet proteins including beta-lactoglobulin. PMID- 7799433 TI - Structural and mechanistic analysis of two refined crystal structures of the pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase. AB - Two refined structures, differing in alkali metal ion content, of the bifunctional, pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase (DGD) are presented in detail. The enzyme is an alpha 4 tetramer, built up as a dimer of dimers, with a subunit molecular mass of 46.5 kDa. The fold of DGD is similar to those of aspartate aminotransferase, omega-amino acid aminotransferase and tyrosine phenol-lyase. The structure has two binding sites for alkali metal ions. DGD with potassium in site 1 (near the active site) and sodium in site 2 (at the surface of the molecule) has been refined against 2.6A resolution data (R factor = 17.6%), and DGD with sodium at both sites has been refined against 2.1 A resolution data (R-factor = 17.8%). The proximity of site 1 to the active site accounts for the dependence of enzyme activity on potassium ions, and the observed active site structural changes caused by ion exchange at this site explain the inhibition of activity by sodium. DGD catalyzes both the decarboxylation of dialkylglycine species and the transamination of L-amino acids in its normal catalytic cycle. The active site structure of DGD is moderately homologous to that of aspartate aminotransferase, which catalyzes only transamination; both the differences and similarities provide mechanistic guidelines for the DGD-catalyzed reactions. Models of the L-isovaline and L alanine external aldimine intermediates suggest mechanisms by which the decarboxylation and transamination reactions could be accomplished within the single active site. Decarboxylation is proposed to be at least partially catalyzed by stereoelectronic activation of the C alpha-carboxylate bond achieved by orienting this bond perpendicular to the plane of the pyridinium ring in the dialkylglycine external aldimine intermediate. Transamination is proposed to be catalyzed by a similar effect on the C alpha-H bond of the L-amino acid external aldimine intermediate, combined with general base catalysis provided by Lys272, in analogy to the mechanism of aspartate aminotransferase. PMID- 7799435 TI - A yeast RNA binding protein that resembles the human autoantigen La. AB - The La protein is a 47 kDa polypeptide that frequently acts as an autoantigen in systemic lupus erythematosus and Sjogren's syndrome patients. A key property of this protein is its association with the U-rich termini of newly synthesized RNA polymerase III transcripts. Here we characterize a 32 kDa protein from Saccharomyces cerevisiae that shows sequence similarity to the N termini of vertebrate La proteins. This yeast protein also functionally resembles La in that it binds preferentially in vitro to RNAs ending with a series of U residues, and at least 53 amino acids can be deleted from the C terminus without impeding this activity. Such RNA binding activity can be detected in crude yeast extracts by immunoprecipitation of ribonucleoprotein particles by an antibody to frog La protein. However, the same antibody fails to react with the 32 kDa protein. In addition, the gene encoding this protein is not essential for viability. Together, these results suggest that additional La homologue(s) exist in yeast. PMID- 7799436 TI - Matching electrostatic charge between DNA and coat protein in filamentous bacteriophage. Fibre diffraction of charge-deletion mutants. AB - The virion of Ff (fd, f1, M13) filamentous bacteriophage consists of a long tube of coat protein subunits in a shingled, helical array, surrounding a genome of circular single-stranded DNA. Modified fd virions have been generated by a mutation (K48A) that removes one positive charge from each coat protein subunit in the C-terminal region of the polypeptide chain facing the DNA. The number of nucleotides in the mutant DNA is unchanged, but the K48A virions are 35% longer than wild-type. We have measured the X-ray diffraction attributable to single virions in hydrated gels of wild-type and K48A bacteriophages. Most of the diffraction pattern shows no significant difference between wild-type and K48A. Since the DNA is only about 12% by weight of the wild-type virion, the diffraction pattern is dominated by the protein contribution, and the absence of significant differences indicates that there are no significant changes in the symmetry or structure of the protein coat. But there is a change in the diffraction pattern in a region where the DNA and protein contributions are comparable. The diffraction pattern of the K48A mutant shows an increase in intensity of one of the weaker equatorial peaks, relative to wild-type, in a region where the protein contribution has negative sign but the DNA contribution has positive sign. This is consistent with a decrease in the ratio of DNA:protein per unit length of the K48A mutant. The results support the view that the protein forms a sheath lined with positive charges interacting electrostatically and non specifically with a negatively charged DNA core of matching charge density. The lower positive charge density lining the capsid in the K48A mutant means that correspondingly fewer nucleotides can be packaged per coat protein subunit, which in turn requires an elongation of the DNA inside the virion. A longer virion is thus required to package the same amount of DNA. Within the error of measurement, the number of positive charges on the protein interacting with the DNA is the same in K48A as in the wild-type, despite the fact that the mutant is 35% longer than the wild-type. PMID- 7799437 TI - In vitro replication of plasmids containing human c-myc DNA. AB - A chromosomal replication initiation zone was previously mapped in cell cultures to the 5' flanking DNA of the human c-myc gene. We have used an in vitro system to examine the replication of a plasmid, pNeo.Myc-2.4, containing 2.4 kb of the c myc initiation zone. In vitro, pNeo.Myc-2.4 generated high levels of DpnI resistant DNA above background incorporation into control plasmids. pNeo.Myc-2.4 replicated semiconservatively to produce supercoiled and relaxed plasmid monomers, and replicative intermediates. [32P]dCMP incorporated into pNeo.Myc-2.4 appeared in Okazaki fragments and low molecular weight strands which matured to full length plasmid DNA, whereas [32P]dCMP incorporated into control plasmids appeared as continuous smears on denaturing gels. Other assays also distinguished the processive replication of pNeo.Myc-2.4 from the dispersive labeling of control plasmids. A pNeo.Myc-2.4 replication time course showed a clear preference for initiation within a restriction fragment containing the c-myc DNA. Two-dimensional electrophoresis revealed that a restriction fragment bearing the c-myc origin zone generated an arc characteristic of replicative intermediates containing a central replication bubble, while vector fragments in the plasmid generated arcs of forked intermediates. Replication bubbles visualized by electron microscopy were centered within the replication initiation zone, approximately 1.4 kb upstream of c-myc promoter P1. Okazaki fragments radiolabeled during in vitro replication showed a switch in the asymmetry of template preference within the initiation zone identified by electron microscopy, two-dimensional electrophoresis and early labeling. These data show that bidirectional, semiconservative replication can originate preferentially in vitro in the 5' flanking DNA of the c-myc gene, and that replicative intermediates present at low levels can be distinguished from molecules generated by competing, repair-type processes. PMID- 7799438 TI - Development of craniofacial musculature in Monodelphis domestica (Marsupialia, Didelphidae). AB - Development of craniofacial muscles of Monodelphis domestica (Marsupialia, Didelphidae) is described. In a period of 4-6 days all craniofacial muscles in M. domestica progress from myoblast condensation, to striated myofibers that are aligned in the direction of adult muscles and possess multiple, lateral nuclei. This process begins 1 to 2 days before birth and continues during the first few days after birth. Compared to other aspects of cranial development, muscle development in M. domestica is rapid. This rapid and more or less simultaneous emergence of craniofacial muscles differs from the previously described pattern of development of the cranial skeleton in marsupials, which displays a mosaic of acceleration and deceleration of regions and individual elements. Unlike the skeletal system, craniofacial muscles show no evidence of regional specialization during development. M. domestica resembles eutherian mammals in the relatively rapid and more or less simultaneous differentiation of all craniofacial muscles. It differs from eutherian taxa in that most stages of myogenesis occur postnatally, following the onset of function. The timing of the development of muscular and skeletal structures is compared and it is concluded that the relatively early development of muscle is not reflected by any particular acceleration of the differentiation or growth of skeletal structures. Finally, the difficulties in accounting for complex internal arrangements of muscles such as the tongue, given current models of myogenesis are summarized. PMID- 7799439 TI - Localization and distribution of gap junctions in normal and cardiomyopathic hamster heart. AB - Gap junctions in mammalian heart function to provide low-resistance channels between adjacent cells for passage of ions and small molecules. It is clear that the almost unrestricted passage of ions between cells, ionic coupling, is required for coordinate and synchronous contraction. This knowledge of gap junction function has made it important to study their properties in normal and abnormal tissues. In the present study, we analyzed gap junction distribution in normal and cardiomyopathic heart tissue utilizing immunofluorescent and electron microscopy techniques. Frozen, unfixed sections of age-matched normal and cardiomyopathic cardiac tissues were immunofluorescently stained using an antibody directed against a specific peptide sequence of the connexin-43 gap junction protein. These studies revealed a characteristic punctate staining pattern for the intercalated discs in normal tissues. Some of the intercalated discs in cardiomyopathic hearts appeared to stain normally; however, others stained diffusely. The pixel intensity distribution of the confocal images demonstrated a marked difference of up to 90% increase in the number of pixels in cardiomyopathic myocardium (CM), yet the pixel intensity of gap junctions had a decrease of approximately 60%. This suggests the possibility that connexin-43 is present in CM cells in significant quantity; however, it does not become localized on the membranes as in normal cells. Electron-microscopic findings corroborate these observations on CM cells by showing an irregular distribution of intercalated discs relatively smaller in size with abnormal orientation and distribution. PMID- 7799440 TI - Allometry of cetacean forelimb bones. AB - This study examines the allometric scaling relationships of the cetacean humerus, radius, and ulna. Bone lengths and diameters were measured for 20 species of odontocete and three species of mysticete cetaceans, representing eight of the nine extant cetacean families. The scaling of individual bone proportions (bone length vs. cranio-caudal diameter, bone length vs. dorso-ventral diameter), and of individual bone dimensions against estimated body mass, are compared to models of geometric and elastic similarity. The geometric similarity model describes the scaling relationship of bone length vs. cranio-caudal diameter and body mass vs. cranio-caudal diameter for the humerus only; geometric similarity also describes the scaling relationship of body mass vs. bone length for all three bones. None of the scaling relationships fits the elastic similarity model. The scaling relationships of bone length vs. dorso-ventral diameter for all three bones, and bone length vs. cranio-caudal diameter for the radius and ulna, exhibit negative allometry, indicating that large bones are less robust than small bones. Negative allometry of structural support elements has not been previously described for terrestrial mammals or plants. The high relative swimming speeds of small delphinids may generate sufficient stresses to require more robust bones relative to those of larger whales. PMID- 7799441 TI - Ca(2+)-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig heart. AB - The mechanism for the regulation of junctional conductance (gj) by Ca2+ was examined in paired ventricular myocytes isolated from guinea pig heart. One cell of the pair was voltage-clamped by a single-patch pipette, and gj was measured after perforation of the non-junctional membrane of the partner cell. The average value of gj under control condition at pCa 9.0 was 181 +/- 13 nS (n = 30). An elevation of calcium concentration ([Ca2+]i) in the intracellular perfusate from pCa 9.0 to pCa 5.7 resulted in a decrease of 32 +/- 5% in gj (n = 18). In myocytes pretreated with W7 (10(-4) M), a similar elevation of [Ca2+]i caused a decrease of only 10 +/- 3% in gj (n = 6), indicating a protective action of W7 against Ca(2+)-mediated electrical uncoupling. W5 (10(-4) M), a non-chlorinated derivative of W7, did not show such a protective action. Calmodulin (10(-5) M) had no effects on gj at pCa 9.0. However, at moderately elevated [Ca2+]i condition at pCa 7.0, calmodulin (10(-5) M) decreased gj by 29 +/- 6% (n = 4). These results suggest that calmodulin may play an important role in the Ca(2+) mediated regulation of gap junctional channel function in the cardiac ventricular cells. PMID- 7799442 TI - Local mitochondrial enzyme activity correlates with myocardial blood flow at basal workloads. AB - To study whether heterogeneous myocardial blood flow relates to the local oxidative capacity of cardiac muscle, local blood flow at resting cardiac workloads and the activity of the mitochondrial enzyme succinate dehydrogenase (SDH) were determined in small regions of the left ventricle of seven anaesthetized, mechanically ventilated, open-chest pigs (25-35 kg). Following injection of radioactive microspheres (15 microns phi) into the left atrium, the heart was rapidly excised and cut into five transverse slices, which were simultaneously freeze-clamped between two aluminum blocks precooled at -80 degrees C. The left ventricle was then subdivided into 84 samples of about 0.9 g. Myocardial blood flow was 0.88 +/- 0.34 ml/min/g wet weight (ww), and SDH activity 1.46 +/- 0.33 mumol/min/g ww (mean +/- S.D., n = 7). Local data were normalized to their respective mean values in each pig, and then pooled. Local blood flow ranged from 0.32 to 1.63 of the mean, and blood flow heterogeneity characterized by the coefficient of variation (CV = S.D./mean) was 18.4%. Normalized local SDH activity ranged from 0.16 to 1.94, with a CV of 21.8%, significantly exceeding measurement error (CV = 4.5%). Local blood flows and SDH activities did not vary among transmural sublayers of the left ventricle, but variation within each sublayer was considerable. In six of the seven pigs, local blood flow correlated (P < 0.05) with SDH activity, with correlation coefficients (r) ranging from 0.26 to 0.54 (for pooled data: r = 0.27, P < 0.0001). When expressed per gram dry weight, heterogeneity of SDH activity increased (P < 0.05), and here also local blood flow correlated with SDH activity in all pigs (for pooled data: r = 0.45, P < 0.0001). Hence, heterogeneity of mitochondrial capacity within cardiac muscle partly explains the heterogeneity of myocardial blood flow, even though myocardial perfusion at rest was studied in relation with a maximal enzyme rate. The low correlation coefficient clearly indicates that at resting workloads other factors also play a role. PMID- 7799444 TI - Effects of a benzothiazepine calcium blocker on electrolyte alteration in human ischemic and reperfused myocardium. AB - Intracellular electrolyte alterations of the myocardial cells from the patients pretreated and non-treated with diltiazem in coronary surgery were measured by means of X-ray microanalysis. Myocardial biopsy specimens were obtained at the right atrial wall at non-ischemia, ischemia and reperfusion periods. The ion concentrations at non-ischemia which is the condition of pre-open heart surgery in patients were: Ca 0.8 +/- 0.05, K 108 +/- 2.3, Na 10 +/- 1.9, Cl 30 +/- 1 (mean +/- S.E., mmol/kg wet weight, n = 100-130), and there were no significant differences for Ca, K, Na and Cl with diltiazem administration. The intracellular Ca increased without diltiazem in reperfusion after open heart surgery. However, there was no Ca increase in either the ischemia or reperfusion states with diltiazem. The K content was significantly lower, and the Na and Cl contents were higher than those of non-ischemia in both ischemia and reperfusion without diltiazem. The K loss, and Na and Cl increases in the reperfusion period were recovered to the levels in the non-ischemia state with diltiazem administration. This study showed that the use of calcium-free cardioplegic solution caused intracellular calcium accumulation in a hypothermic global ischemic and reperfused conditions during coronary surgery, whereas, diltiazem could suppress the calcium accumulation. The alterations of potassium, sodium and chlorine were also favourable in patients with diltiazem. The possible mechanism of the effects of diltiazem on the element alterations of myocardium are discussed. PMID- 7799443 TI - Mitochondrial gene expression during bovine cardiac growth and development. AB - The expression of both mitochondrial and nuclear genes encoding enzymes involved in electron transport and oxidative phosphorylation was examined in bovine cardiac tissue during early growth, development and aging. The steady state level of mRNAs for mitochondrial genes including ATPase 6. COXII and cyt b increased 2.5-4-fold relative to early fetal levels in late fetal and young adult tissues and showed a marked decline (30-50%) in older adult tissues. Similar results were found with the nuclear genes, COXVB and ATP-beta synthase showing coordinate regulation of the two genomes. An increase in mtDNA copy number correlated with the increase in transcript level. Enzyme activity levels for NADH dehydrogenase and cytochrome c oxidase showed a similar trend, albeit of lesser magnitude. These activity levels contrasted with the activity level of an entirely nuclear encoded mitochondrial enzyme, citrate synthase, which increased not only throughout development but in the older adult tissue. This study indicates that there is a pattern of increasing mitochondrial and nuclear gene expression for OXPHOS enzymes in developing cardiac tissue and decreasing OXPHOS gene expression in the aging heart. PMID- 7799445 TI - Over-expression of CUG- or AUG-initiated forms of basic fibroblast growth factor in cardiac myocytes results in similar effects on mitosis and protein synthesis but distinct nuclear morphologies. AB - Initiation of translation from alternate codons in the same mRNA results in multiple forms of basic fibroblast growth factor (bFGF). High molecular weight species of bFGF make use of leucine translation initiation sites located upstream of the methionine residue used to produce the 18 kiloDalton (kDa) form. Although the addition of exogenous 18 kDa bFGF is known to stimulate DNA synthesis and proliferation of several cell types including embryonic chicken cardiac myocytes, little is known about the role of high molecular weight forms of bFGF. We modified the rat bFGF cDNA to yield high (22/21.5 kDa) or low (18 kDa) molecular weight species of bFGF. Expression of 22/21.5 kDa or 18 kDa bFGF in transfected embryonic chicken ventricular myocyte cultures was confirmed by protein blotting. Expression of both high and low molecular weight species of bFGF was associated with (i) a three-fold increase in overall thymidine incorporation as well as cardiomyocyte labelling index (fraction of cardiomyocyte nuclei incorporating tritiated thymidine); (ii) a two- to three-fold increase in cell number; (iii) an eight-fold increase in protein synthesis; and (iv) a three-fold decrease in myosin accumulation. Subcellular localization of bFGF in the transfected myocyte cultures was also assessed by immunofluorescence microscopy. Over-expression of cDNAs yielding high molecular weight bFGF resulted in predominantly nuclear bFGF staining. By contrast, both cytoplasmic and nuclear staining were observed following over-expression of 18 kDa bFGF. Over-expression of 22/21.5 kDa bFGF was associated with the formation of multiple DNA-containing "clumps" resembling condensed chromatin in cardiac myocyte nuclei. These DNA "clumps" were not observed in cardiac myocyte cultures over-expressing 18 kDa bFGF. These data indicate that over-expression of high as well as low molecular weight forms of bFGF can stimulate cardiac myocyte proliferative potential and decrease myosin accumulation. However, these forms possess distinct subcellular localizations and can have different biological functions in the nucleus. PMID- 7799446 TI - Effect of streptokinase on human neutrophil function in vitro and in patients with acute myocardial infarction. AB - The clinical benefit of streptokinase (SK) in the treatment of patients with acute myocardial infarction may be influenced by effects other than myocardial reperfusion per se. Polymorphonuclear leucocytes (PMNs) have been hypothesized to participate in the process of reperfusion injury in the postischemic myocardium. The purpose of the present study was therefore to investigate the effect of SK on human PMN function in vitro, and ex vivo in patients with acute myocardial infarction. SK was not in itself chemotactic to PMNs, and preincubation with SK did not alter the chemotactic response of PMNs to formyl-Met-Leu-Phe (FMLP) or zymosan-activated serum. However, incubation of fresh citrated plasma with SK resulted in the generation of chemotactic activity, and this effect was dependent on complement activation by SK. In experiments with PMNs from 20 health donors, preincubation of plasma and SK, followed by incubation with PMNs, primed the cells for enhanced chemiluminescence response to FMLP. The PMN priming by SK+plasma showed considerable interindividual variation, and was not mediated by a direct action of plasmin on PMNs. In 10 patients with acute myocardial infarction treated with SK, a reduction in superoxide production by PMNs was observed immediately following SK. The results suggest that SK modulates human PMN function in vivo, and these effects may influence the therapeutical value of this agent. PMID- 7799448 TI - Influence of cell isolation and recording technique on the voltage dependence of the fast cardiac sodium current of the rat. AB - We measured macroscopic sodium currents (INa) in preparations from adult rat ventricle under four different conditions (I-IV): using the cell attached configuration of the tight-seal patch clamp technique on cells isolated with either trypsin followed by collagenase (I) or with collagenase only (II), and using the loose patch technique on cells isolated with collagenase (II) as well as on multicellular preparations not subjected to enzyme treatment (IV). The voltage dependence of the steady-state activation of INa as well as of the steady state inactivation differed significantly among condition I and II. Moreover, the recordings were voltage shifted in comparison to the recording condition III and IV. The potentials of half maximal activation and inactivation were: [sequence data: see text] The shift of inactivation was time dependent and continued after 3-5 min after the seal formation in condition I, but not in condition II. No time dependent shift was found in III and IV. We conclude, that the voltage dependence of cardiac sodium current is shifted by gigaseal patch recording. The degree of this shift depends on the type of enzymatic isolation procedure, with trypsin causing more pronounced effects than collagenase. The cell isolation itself seems not to interfere with the voltage dependence of INa, since loose patch recordings from multicellular preparations and from single cells isolated with collagenase show no obvious differences. PMID- 7799447 TI - Contribution of endothelium and cardiomyocytes to hypoxia-induced adenosine release. AB - The cellular source and role of adenosine in hypoxia-induced coronary vasodilatation was investigated. The endothelial adenine nucleotides of Langendorff-perfused rat hearts were prelabelled by perfusion with [3H]adenosine and the changes in specific radioactivities were employed to identify the source of the adenine compounds released. The contribution of ecto-5'-nucleotidase was evaluated in perfusions with the inhibitor alpha,beta-methylene adenosine diphosphate (AOPCP). Absorbance of the effluent perfusate at 260 nm was monitored continuously as a convenient means of detecting the output of total purines, and it showed a good correlation with HPLC-measured purines (r = 0.72, P < 0.001). Coronary flow increased sharply in hypoxia but tended to decrease after 2 min, while effluent radioactivity and absorbance increased steadily. The radioactivity to-absorbance ratio and the specific radioactivity of chemically measured total purines began to increase after 3 min. The changes in effluent concentrations of adenosine and inosine were much more prominent than those in free purines. The specific radioactivity of adenosine decreased sharply at the onset of hypoxia which indicates that hypoxia affects mainly working cardiomyocytes. This also means that endothelial adenosine release is delayed if compared to coronary vasoregulation. Although the inhibition of ecto-5'-nucleotidase caused a decrease in the release of adenosine and adenine moiety label from the heart it is most likely that adenosine was mainly derived from intracellular sources, because the hypoxia-induced increase in the concentration of adenosine was more excessive than that of AMP. In addition, AOPCP decreased the basal work load and coronary flow of the heart, slightly attenuated the hypoxia-induced flow increase and prevented adenylate loss during hypoxia. Thus, the data emphasize the role of cardiomyocytes in adenosine production and coronary vasoregulation. PMID- 7799449 TI - Hypothesis: apoptosis may be a mechanism for the transition to heart failure with chronic pressure overload. PMID- 7799450 TI - Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. AB - This study was undertaken to evaluate the direct cardioprotective effect of trimetazidine (TMZ), an anti-anginal drug devoid of haemodynamic action, on isolated myocytes. Cultured rat ventricular myocytes were treated with the drug 16 h and 1 h before the experiments. The drug-treated cells and control cells were placed in a substrate free medium and submitted in a specially designed device to either normoxia (N4), or hypoxia (150 min, H2.5, or 240 min, H4), or 150 min hypoxia followed by 90 min reoxygenation (HR). The treatment of the cells with TMZ (5 x 10(-4) M) resulted in a significant decrease of lactate dehydrogenase (LDH) leakage (-58% in H2.5, -36% in H4 and -37% in HR). The LDH release provoked by oxidizing agents. H2O2 and 13-s-HpOTrE (13(S) hydroperoxyoctadecatrienoic acid) during post-hypoxic reoxygenation was also lowered by TMZ. However, this effect reflected the beneficial action of TMZ during hypoxia since the drug was not efficient in altering the LDH leakage induced by the oxidizing agents in normal conditions. Moreover, the hypoxia induced decrease of ATP content was not affected by TMZ, and resynthesis of ATP during substrate-free reoxygenation was similar in TMZ-treated and control cells. The respiration parameters have been studied in rat heart mitochondria isolated from control and TMZ-treated rats, in the presence or absence of TMZ in the respiration medium (10(-4) M). The main result was a rapid and potent inhibition of palmitoylcarnitine oxidation, when TMZ was added to the respiration medium. The chronic treatment only resulted in a slight alteration of pyruvate oxidation. In conclusion, a pre-treatment of ventricular myocytes with TMZ resulted in an increased cell resistance to hypoxic stress, as evidenced by LDH leakage. This cytoprotective effect of TMZ should not be mediated through an antioxidant activity, but could be related to a modification of lipid metabolism. PMID- 7799451 TI - Explaining load dependence of ventricular contractile properties with a model of excitation-contraction coupling. AB - A theory is present which accounts for a very broad range of ventricular properties that have been noted in recent experiments. The theory is based upon a four-state biochemical scheme that accounts for the dynamic interaction between calcium, actin and myosin which includes a calcium-free force generating complex between actin and myosin. This original scheme was supplemented by incorporating two additional basic properties of cardiac muscle: length dependence of calcium binding affinity and load dependence of force generation. The biochemical scheme was used to provide the force-length-time properties of cardiac muscle which were used to construct a ventricle via a spherical geometry. In addition to being able to accurately interrelate previously measured calcium and muscle force transients, this theory was able to account for many fundamental aspects of ventricular performance including: a realistic contractility dependent curvilinearity of the end-systolic pressure-volume relationship: enhancement of contractile strength on ejecting compared to isovolumic beats; improved contractile efficiency on ejecting as compared to isovolumic beats; appropriate load-dependent changes in time to peak pressure, time constant of relaxation and duration of contraction on isovolumic and ejecting beats; realistic estimated time course of tension-dependent heat generation. The explanation for these phenomena were explored within the context of the theory and presented in detail. PMID- 7799452 TI - Chronic administration of nicardipine attenuates myocardial stunning in isolated rabbit hearts. AB - The purpose of this study was to evaluate the effects of the chronic administration of a calcium channel blocker, nicardipine, on systolic and diastolic alterations occurring during myocardial stunning in isolated rabbit hearts. Rabbits were pretreated with nicardipine 20 mg (O.I.D.) for 30 days. Then hearts were isolated (group II) and compared with control hearts (group I) in their response to 20 min of global ischemia and 30 min of reperfusion. Coronary flow and heart rate were kept constant. Left ventricular isovolumic developed pressure (LVDP), its first derivative (dP/dt), and end diastolic pressure (LVEDP) were measured. After isolation, no statistically significant changes were detected in LVDP, +dP/dtmax, LVEDP, or coronary resistance in hearts of rabbits with or without the pharmacological intervention. Early after the onset of reperfusion, LVDP and +dP/dtmax partially recovered in a similar way in groups I and II. Late in reperfusion LVDP stabilized at 48 +/- 7% in group I and 71 +/- 6% in group II (P < 0.05) and +dP/dtmax stabilized at 56 +/- 7% and 79 +/- 6% (P < 0.05), respectively. Diastolic dysfunction was manifested by a 217 +/- 39% increase in LVEDP (P < 0.05) in group I, and 140 +/- 31% in group II (P < 0.05). The isovolumic relaxation time constant (tau, tau) increased from 70 +/- 5 to 151 +/- 27 ms (P < 0.05), and from 66 +/- 6 to 97 +/- 10 ms. (NS) in groups I and II, respectively at 5 min of reperfusion. This relaxation parameter returned to normal values in the late reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799453 TI - Comparison of the action potential prolonging and positive inotropic activity of DPI 201-106 and BDF 9148 in human ventricular myocardium. AB - The aim of our study was to compare the effects on contractile function and action potential duration of the new Na+ channel modulator BDF 9148 with the parent compound DPI 201-106 in human ventricular myocardium. Right ventricular papillary muscles were obtained from explanted hearts of heart transplant recipients or from non-failing hearts not suitable for transplantation. BDF 9148 induced an increase in force of contraction that was accompanied by prolongation of action potential duration. The action potential duration prolonging effect of BDF 9148 was not significantly different to that of DPI 201-106. The effects of BDF 9148 were similar in muscles obtained from non-failing and failing hearts. Using Na(+)-sensitive electrodes, we have demonstrated that the positive inotropic effect of BDF 9148 is accompanied by an increase in intracellular Na+ activity. Our results indicate: (i) that BDF 9148 is as effective as DPI 201-106 in increasing force of contraction and prolonging action potential duration in human ventricular myocardium: (ii) that BDF 9148 is effective in enhancing force of contraction, in spite of heart failure; (iii) that the positive inotropic effect is related to an increased Na+ load; and (iv) due to action potential duration prolongation, changes in Q-T interval of the electrocardiogram could be possible during in vivo use of BDF 9148. PMID- 7799455 TI - Ocular manifestations of diabetes mellitus (continuing education credit). AB - 1. Within 15 to 20 years of being diagnosed as having diabetes mellitus, 90% of patients will have some degree of diabetic retinopathy and 25% will have proliferative diabetic retinopathy. 2. The majority of the cases of blindness from diabetic retinopathy could be prevented or significantly delayed by timely and appropriate management of diabetic retinopathy. 3. Until a cure for diabetes mellitus is discovered, all patients with diabetes mellitus should receive ophthalmic evaluation soon after the diagnosis is made. PMID- 7799456 TI - A key to preventing diabetic retinopathy: the link between nutrition and blood sugar. AB - 1. Complications associated with diabetes include diabetic retinopathy, nephropathy, and neuropathy. The most important factor in preventing or delaying chronic complications associated with diabetes is blood glucose control, which is achieved through diet, insulin therapy, and self-monitoring. 2. The American Diabetes Association's Exchange System is useful for the motivated, well-educated patient, although its complexity can lead to noncompliance. The system assists in meal planning and permits flexible selection from a variety of foods, taking into account each food's total protein, fat, and carbohydrate content. 3. Adequate calories and nutrients must be provided, along with behavioral modifications and medical treatment, to achieve optimal health. PMID- 7799454 TI - Protective effects of the SOD-mimetic SC-52608 against ischemia/reperfusion damage in the rabbit isolated heart. AB - An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC 52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide. PMID- 7799457 TI - Exercise options for people with diabetic eye complications. AB - 1. The first rule of exercise prescription is that the benefits must outweigh the risk. 2. It is recommended that patients with diabetic complications undergo a thorough physical examination prior to beginning an exercise program. 3. A program of daily, moderate aerobic exercise helps to maintain or improve cardiovascular functioning while improving insulin sensitivity and blood sugar control. PMID- 7799458 TI - Amaurosis fugax challenges: best met by multispecialty approach to management. AB - 1. Amaurosis fugax (AF) refers to transient, reversible loss of vision, typically monocular and of short duration. 2. Patients with AF present a diagnostic and therapeutic challenge, frequently requiring a multispecialty approach to management. It is important to determine whether or not there is an ocular cause of the problem. 3. In the absence of eye findings to explain the symptoms, the internist must direct the workup toward cardiogenic hypotension, migraine, carotid or vertebral-basilar artherosclerotic disease, cardiac embolic disorder, and other potential causes. PMID- 7799460 TI - Origins of beliefs and attitudes toward blindness. PMID- 7799459 TI - Amblyopia: etiology, diagnosis, and treatment. American Academy of Ophthalmology. AB - 1. Sometimes called "lazy eye," amblyopia is poor vision in an eye that did not develop normal sight during early childhood. Amblyopia is common, affecting approximately 2 or 3 out of every 100 people. The best time to correct amblyopia is during infancy or early childhood. 2. Amblyopia has three major causes: strabismus (misaligned eyes), unequal focus (refractive error), and cloudiness in the normally clear eye tissues. 3. To correct amblyopia, a child must be made to use the weak eye. This is usually done by patching or covering the strong eye. Amblyopia cannot be cured by treating the cause alone; the weaker eye must be made stronger in order to see normally. PMID- 7799461 TI - Self-assessment quiz. Sub-hyaloid hemorrhage. PMID- 7799462 TI - Positioning daily disposables in the contact lens practice. PMID- 7799463 TI - Lower tibial osteotomy for osteoarthritis of the ankle. AB - Ankle arthrodesis is still the treatment of choice for most disabling arthritic ankles. But in spite of its popularity, ankle arthrodesis has many disadvantages, including long immobilization, a high pseudoarthrosis rate, and load shift with increased stress on neighboring joints of ankle. Lower tibial osteotomy is one of the methods which attempts to halt ankle arthritis in the intermediate stage and trying to prevent ankle arthroadesis. From Aug. 1989, we performed 8 operations of lower tibial osteotomy in our hospital on intermediate arthritic ankle which included 4 post-traumatic ankle arthritis and 4 ankle osteoarthritis. The patient's ages ranged from 21y/o to 72y/o with an average of 41.6y/o. The mean time of followed up was 31.7 months. The patients were evaluated by the ankle functional scale preoperatively and during their followed up. The average preoperative functional score was 49.6 and the last follow up score was 88.5 which is increasing year by year. Significant improvement occurred in function and pain relief and there was improvement of ankle motion in most patients except one. Complications included late infection in 1 patient and implant failure with subsequent revision surgery due to overcorrection in 1 patient. No nonunion was noted. Although our series was small, we had encouraging short-term results. We believe lower tibial osteotomy, by pressure redistribution on the joint surface, is an alternative for the treatment of ankle osteoarthritis and may save or delay arthritic ankle from the fate of fusion. PMID- 7799464 TI - Radionuclide esophageal transit test in the detection of esophageal dysmotility in Parkinson's disease. AB - Thirty-three patients of idiopathic Parkinson's disease (PD) and 25 volunteers were admitted to the study for comparison. Esophageal motility including esophageal mean transit time (MTT), residual fraction (RF), and retrograde index (RI) of the two groups were evaluated and calculated by the radionuclide esophageal transit test. The results show that 12% (4/33) of the cases of PD were abnormal in proximal, 15% (5/33) in middle, 0% (0/33) in distal, and 12% (4/33) in total MTT, as well as 6% (2/33) in RF, and 24% (8/33) in RI. In addition, the patients with high H-Y scale scores had a higher incidence of abnormality in proximal MTT than those with low scale (P < 0.05 by a Fisher's exact test). We consider that the radionuclide esophageal transit test has potential as an effective, simple and noninvasive screening tool to detect abnormal esophageal motility in patients suffering from Parkinson's disease. PMID- 7799465 TI - Abdominal wall hernia complicating continuous ambulatory peritoneal dialysis. AB - Continuous ambulatory peritoneal dialysis (CAPD) is a well-established treatment modality for end-stage renal disease. Abdominal wall hernia is not uncommon in patients on CAPD. Two factors are responsible for the occurrence of these hernias: anatomically weak sites and increased intraperitoneal pressure by the dialysate. Abdominal wall hernia was reviewed in 44 patients on CAPD from 1987 through 1991. Eight abdominal hernias (5 inguinal, 2 incisional and 1 umbilical) were found during CAPD treatment (18.18%). Surgical treatment was applied in 6 symptomatic hernias (5 inguinal and 1 incisional). After surgery, 5 patients returned to CAPD without recurrence and the remaining one died of strangulated incisional hernia. Our series shows that: (1) a detailed examination of the preexisting hernia and repair prior to CAPD treatment are suggested. (2) symptomatic abdominal wall hernia should be evaluated carefully and treated promptly. (3) awareness of the complication of these hernias can reduce the morbidity and mortality. PMID- 7799466 TI - [A replication of multidimensionality of activities of daily living(ADL): on the elderly in southern Taiwan]. AB - The purpose of the present study is to test whether Wolinsky and Johnson's declaration that activities of daily living (ADL) can be divided into three subdimension (basic, household, and advanced ADL), and whether these three dimensions could be replicated or not in Taiwan. Furthermore, to confirm the relationship of advanced ADL and cognitive function. The analyses were based on a sample of 790 respondents over 65 years of age who lived in the community of Southern Taiwan. Fourteen items were adopted from the ADL section of OARS Multidimensional Functional Assessment (OMFAQ, Chinese Version) for performing a confirmatory factor analysis. In addition, 10 items from the Short Portable Mental Status Questionnaire (SPMSQ) were selected for a zero-order correlation and regression analyses to examine the relationship between the advanced ADL and cognitive function. The results support Wolinsky & Johnson's assertion, but some items that are comprised in each factor structure, however, are not consistent with those in Wolinsky & Johnson's study, such as taking medicine, grooming, eating, shopping, and transporting. Significant correlation between advanced ADL and cognitive function was also confirmed in the study (r = 0.612, p < 0.05). PMID- 7799467 TI - [Postpartum adjustment of women who were home during the "traditional Chinese one month postpartum period of confinement" and those who were in maternity care centers]. AB - The purpose of this study was to explore the difference in postpartum adjustment between women who were at home for there "doing the month" and those who stayed in a maternity care center. A repeated measures design was conducted, with data collected at 1 and 4 weeks postpartum. A total of 120 postpartum women participated in this study. Data were analyzed by factor analysis to determine the relationships within categories of postpartum strssors and depression. Then, the data were analyzed by 2 x 2 repeated measure MANOVA to determine the variations among groups and time. The results indicated that women who were in maternity centers for the "doing the month" perceived significantly higher stress than did the home group, and that women perceived higher stress at 4 weeks postpartum than at 1 week postpartum. Factor analysis of the data defined four categories of postpartum stress. It was found that women at maternity care centers perceived significantly higher stress from factors named, "stress from lacking of support system" and "stress from identifying maternal role". In addition, women doing the month at maternity care centers showed significantly higher depression level than women doing the month at home. However, there is no significant difference in postpartum stress and postpartum depression between time 1 (1 week postpartum) and time 2 (4 weeks postpartum). PMID- 7799468 TI - Imaging diagnosis of cavernous hemangioma of the rib--one case report and review of the literature. AB - Osseous hemangioma is a benign neoplasm, rarely located in the ribs. A 56-year old female patient without specific complaint had a large extrapleural lesion on chest posteroanterior radiograph. Expansile destruction of left seventh rib and relatively fine trabeculation were noticed in the mass from plain roentgenogram and computed tomography (CT). Contrast enhancement in noncalcified component of the lesion was revealed. Pleural effusion, lung parenchymal or mediastinal abnormality were not identified. Resection of the lesion with part of the originating rib was carried out. The pathologic diagnosis was cavernous hemangioma. We present a case with a large rib hemangioma which often leads to difficulty in radiologically differential diagnosis with other common malignant rib tumors. We also review the literature about hemangioma and malignant neoplasms of the ribs. PMID- 7799469 TI - Subependymal giant cell astrocytoma with tuberous sclerosis--case report. AB - Tuberous sclerosis is a rare disease of autosomal dominant inheritance and may affect any organ, and less than 2% have a subependymal giant cell astrocytoma. In the present report, a 6-year-old girl with clinical features of tuberous sclerosis had an intraventricular tumor. CT scan and MRI of brain showed a tumor in the lateral ventricles extended into the Foramina of Monro and third ventricle causing severe hydrocephalus. She underwent left frontal craniotomy with partial removal of the tumor. The pathology was subependymal giant cell astrocytoma. Patient's neurological condition improved postoperatively and postoperative CT scan showed no hydrocephalus. Clinical and radiological follow-up of patients with tuberous sclerosis who had subependymal nodules in early childhood is important due to its possibility of subsequent transformation into intraventricular tumor. PMID- 7799470 TI - Factors affecting speed in human-powered vehicles. AB - It is shown how to derive the appropriate cubic equation relating power and the effects of friction, gradient and wind resistance on the speed of a human-powered vehicle (HPV). The effects of gradient and wind resistance are explored for parameters representing a typical racing cyclist. The principal conclusion may be summarized as follows: for optimum performance in a time trial, there should be no wind and the course should be level. Any deviation from these conditions will produce a decrement in performance. PMID- 7799471 TI - An examination of the cohesion-performance relationship in university hockey teams. AB - The objective of this study was to assess, using the Group Environment Questionnaire, whether team cohesion in university-level field hockey was a cause for, or an effect of, successful performance. A quasi-experimental longitudinal design with cross-lagged correlational analysis was adopted and measures of cohesion and performance were taken midway and later in the season. The results of the synchronous correlations showed a positive relationship (with good stationarity) between team cohesion and performance outcome. Although non significant cross-lagged differentials indicated a circular relationship, the magnitudes of both the cross-lagged correlations and the partial correlations, together with multiple-regression analyses, revealed that the stronger flow was from cohesion to performance. The socially oriented aspects of cohesion, in particular, had significant associations with performance. The results imply that cohesion-performance relationships should be examined within a circular model, in which cohesion and performance are interdependent. PMID- 7799472 TI - Aerobic exercise and Type A behaviour. AB - The Type A behaviour pattern is a well-documented, if controversial, risk factor for coronary heart disease. Surprisingly, relatively little work has been reported on ways of modifying this behaviour pattern. Aerobic exercise, with its demonstrated benefits for both cardiovascular reactivity and psychological 'well being', is a promising treatment. The literature is reviewed and recommendations are made for practical applications and future research. PMID- 7799473 TI - Accumulated oxygen deficit and short-distance running performance. AB - Recent studies have suggested that determining the accumulated oxygen deficit (AOD), in units of oxygen equivalents per kilogram body mass (ml O2 Eq.kg-1), during a short exhaustive run, may represent a non-invasive measure of anaerobic metabolism. However, there is little information either on the reproducibility of the laboratory determination or its relationship with human performance. The purpose of the present investigation was to determine the reproducibility of AOD during inclined treadmill running (study 1), and to examine its relationship with short-distance running performance (study 2). Twelve volunteers (11 males, 1 female) took part in study 1 and AOD was determined (relative exercise intensity approximately 120% VO2 max) on two separate occasions at a treadmill inclination of 10.5%; the laboratory-measured AOD values were 65.2 +/- 10.9 vs 66.3 +/- 12.5 ml O2 Eq.kg-1, respectively (r = 0.94, P < 0.01). A second subject group (10 males, 4 females) undertook study 2, which investigated AOD values and track times over 100, 400 and 800 m. The mean calculated AOD value was 66.1 +/- 12.0 ml O2 Eq.kg-1, and the average track times were 13.6 +/- 1.3, 60.9 +/- 6.8 and 138.8 +/- 18.5 s for the 100, 400 and 800 m, respectively. The r-values for the relationship between AOD and track time were -0.88, -0.82 (P < 0.01) and -0.61 (P < 0.05) for the 100, 400 and 800 m, respectively. The results of the present study suggest that the AOD (ml O2 Eq.kg-1) is a unique and reproducible physiological characteristic which is strongly correlated with sprint capacity. PMID- 7799474 TI - Aerobic and anaerobic contributions to exhaustive high-intensity exercise after sleep deprivation. AB - The purpose of this study was to determine the effect of one night's sleep loss on the performance of high-intensity exercise and on the contribution of anaerobic and aerobic energy systems to the exercise. Seven males and seven females performed an all-out cycling exercise test during baseline testing and then on three consecutive days after a sleepless night. The work rates were 5.0 W kg-1 for the females and 6.0 W kg-1 for the males. The aerobic contribution was determined based on measured VO2 and the anaerobic contribution was determined by subtraction of the aerobic contribution from the total amount of work performed. The results of baseline tests and of tests performed following sleep loss were compared for evidence of an effect of sleep deprivation. The 25-30 h of sleep deprivation did not affect total work, the anaerobic contribution or the aerobic contribution (all P > 0.1), although there was a tendency (P = 0.13) for mean VO2 to decrease after the sleepless night. There were no interaction effects involving sex on total work, the anaerobic contribution or the aerobic contribution (all P > 0.1). The mean (+/- S.E.M.) values for total work (kJ) performed were: baseline, 21.9 +/- 2.7; after sleep loss, 21.1 +/- 2.5 (day 1), 21.7 +/- 2.5 (day 2), and 21.9 +/- 2.7 (day 3). It is concluded that, in both males and females, there are no changes in the contributions of the aerobic and anaerobic energy systems to high-intensity exercise performed following the loss of one night's sleep. PMID- 7799475 TI - Effects of resistance exercise and cycling on recovery blood pressure. AB - The purpose of this investigation was to examine blood pressure responses during recovery from resistance exercise and cycling. Seven normotensive volunteers (5 males, 2 females) were studied. Resistance exercise consisted of three sets of five exercises (arm curl, hamstring curl, squat, 'lat pull' and bench press) on four occasions: (1) twice using 40% one-repetition maximum (1RM) for 20-25 repetitions, and (2) twice using 70% 1RM for 8-10 repetitions. The subjects also cycled for 25 min at 70% of heart rate reserve on two occasions. Measurements of recovery systolic and diastolic blood pressure were made at 2, 5, 10, 15, 30 and 60 min post-exercise with subjects in the seated position. Analysis of variance with repeated measures revealed that there were no significant differences between recovery blood pressures after the cycling or resistance exercise treatments. Average systolic blood pressure after 2 min of recovery was elevated (115 +/- 2 mmHg, P < 0.0001) and diastolic blood pressure was depressed (48 +/- 3 mmHg, P < 0.0001) in comparison to previously determined baseline values. Systolic blood pressure at 5 min and diastolic blood pressure at 15 min post exercise were not significantly lower than resting baseline values, and remained so after 60 min of recovery. It was concluded that different intensities of resistance exercise produce the same blood pressure response in recovery and that these changes were approximately equal to those produced by cycling. PMID- 7799476 TI - The physiological and ventilatory responses to repeated 60 s sprints following sodium citrate ingestion. AB - This study examined the influence of sodium citrate on changes in selected blood, ventilatory and performance variables in response to intermittent sprint exercise. Eight moderately active male students completed three tests over a 6 day experimental period. The first test involved incremental exercise to determine VO2 max, while the second and third tests were identical in nature and involved five 60 s sprints cycling against 0.075 kg kg-1 body mass (BM); each of the five sprints was separated by 5 min passive seated recovery. Three days separated the VO2 max test and first interval test, while a further 3 days elapsed between the first and second interval tests. Ninety minutes prior to each interval test, the subjects consumed either a solution of sodium citrate (0.5 g kg-1 BM) or a placebo solution (1 g of calcium carbonate and 4 mg of sodium chloride). These were randomly administered in a double-blind crossover procedure so that every subject consumed each solution prior to the interval test over the 6 day period. Measures of work, VE, VO2, VCO2, post-exercise plasma lactate, and changes in both venous blood pH and venous blood bicarbonate (HCO3-) were measured during each interval test. Although analysis of variance failed to identify differences in performance between the two solutions, both exercise VCO2 and changes in venous blood HCO3- were higher in the citrate condition (P < 0.05). In addition, both peak post-exercise plasma lactate concentrations and post-exercise venous blood pH were significantly higher following citrate ingestion. Although these data are consistent with greater clearance of lactate and H+ from the active muscle cells following citrate ingestion, performance between the two trials was the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799477 TI - Loss of exercise training-induced bradycardia with continued improvement in fitness. AB - In sedentary individuals, the decrease in heart rate (HR) at a respiratory exchange ratio (R) of unity (HR/R = 1) is lost after 8 weeks of moderate intensity exercise training. The purpose of this investigation was to examine the effect of training on HR/R = 1, using the exercise intensity (EI) at R = 1 (EI/R = 1) and the HR at a set EI (HR/EIS). In nine healthy volunteers, these indices showed small measurement variability and detected changes associated with 16 weeks of training in that EI/R = 1 and VO2/R = 1 increased, whereas HR/EIS, HR/R = 1 and HR/VO2 decreased. All of these changes were reversed when training ended. In a second trial in a further nine volunteers, the training programme was extended to 20 weeks, and again showed that the decrease in HR/R = 1 failed to progress after 8 weeks despite continued changes in other indices (increases in VO2/R = 1 and decreases in HR/VO2 elevation). The loss of HR/R = 1 decrease was attributed to equal and opposite effects on HR/EIS and EI/R = 1. However, the decreases in HR/EIS showed the same trend as HR/R = 1, with a lack of progression beyond 8-16 weeks. These findings suggest that different indices of cardiorespiratory fitness have different patterns of change and limitations during training. Those which rely on decreases in submaximal HR fail to detect adaptation during continued training. Using submaximal exercise test indices, detection of such changes is better achieved by the measurement of decreases in HR/VO2 elevation and increases in VO2/R = 1 values. PMID- 7799478 TI - From the Centers for Disease Control and Prevention. Mortality patterns--United States, 1992. PMID- 7799479 TI - From the Centers for Disease Control and Prevention. Infant mortality--United States, 1992. PMID- 7799480 TI - From the Centers for Disease Control and Prevention. Prevalence of selected risk factors for chronic disease by education level in racial/ethnic populations- United States, 1991-1992. PMID- 7799481 TI - Forecasting physician workforce requirements. PMID- 7799482 TI - Forecasting physician workforce requirements. PMID- 7799483 TI - Forecasting physician workforce requirements. PMID- 7799484 TI - Forecasting physician workforce requirements. PMID- 7799485 TI - Forecasting physician workforce requirements. PMID- 7799486 TI - A conversation with my mother. PMID- 7799487 TI - Editorial peer review. PMID- 7799489 TI - Hierarchical authorship. PMID- 7799488 TI - LDL density and atherosclerosis. PMID- 7799490 TI - Silicone breast implants and risk of cancer? PMID- 7799491 TI - The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. AB - OBJECTIVE: Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. DESIGN: Prospective cohort study with a follow-up of 28 days or until discharge if earlier. SETTING: Three intensive care units and three general wards in a tertiary health care institution. METHODS: Patients were included if they met at least two of the criteria for SIRS: fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count. MAIN OUTCOMES MEASURES: Development of any stage of the biologic response to infection: sepsis, severe sepsis, septic shock, end-organ dysfunction, and death. RESULTS: During the study period 3708 patients were admitted to the survey units, and 2527 (68%) met the criteria for SIRS. The incidence density rates for SIRS in the surgical, medical, and cardiovascular intensive care units were 857, 804, and 542 episodes per 1000 patient-days, respectively, and 671, 495, and 320 per 1000 patient-days for the medical, cardiothoracic, and general surgery wards, respectively. Among patients with SIRS, 649 (26%) developed sepsis, 467 (18%) developed severe sepsis, and 110 (4%) developed septic shock. The median interval from SIRS to sepsis was inversely correlated with the number of SIRS criteria (two, three, or all four) that the patients met. As the population of patients progressed from SIRS to septic shock, increasing proportions had adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and shock. Positive blood cultures were found in 17% of patients with sepsis, in 25% with severe sepsis, and in 69% with septic shock. There were also stepwise increases in mortality rates in the hierarchy from SIRS, sepsis, severe sepsis, and septic shock: 7%, 16%, 20%, and 46%, respectively. Of interest, we also observed equal numbers of patients who appeared to have sepsis, severe sepsis, and septic shock but who had negative cultures. They had been prescribed empirical antibiotics for a median of 3 days. The cause of the systemic inflammatory response in these culture-negative populations is unknown, but they had similar morbidity and mortality rates as the respective culture-positive populations. CONCLUSIONS: This prospective epidemiologic study of SIRS and related conditions provides, to our knowledge, the first evidence of a clinical progression from SIRS to sepsis to severe sepsis and septic shock. PMID- 7799492 TI - Use of the medical futility rationale in do-not-attempt-resuscitation orders. AB - OBJECTIVE: To describe the use of the medical futility rationale in do-not attempt-resuscitation (DNAR) orders written for medical inpatients. DESIGN: Structured interviews with medical residents. METHODS: Second- and third-year internal medicine residents (n = 44) were telephoned weekly and briefly interviewed about each patient who received a DNAR order in the preceding week. SETTING: Two university-affiliated hospitals: a veterans affairs medical center and a municipal hospital. PATIENTS: One hundred forty-five medical inpatients for whom DNAR orders were written during their hospitalization. RESULTS: Residents stated that the medical futility rationale applied for 91 patients (63%), but this rationale was invoked independent of patient or surrogate choice for only 17 patients (12%). Of the 91 patients for whom futility applied, both quantitative futility (low probability of success) and qualitative futility (poor quality of life if cardiopulmonary resuscitation [CPR] were performed) applied to 45 (49%), quantitative futility alone to 30 (33%), and qualitative futility alone to 16 (18%). Residents report that they discussed resuscitation issues with all communicative patients for whom the medical futility rationale was invoked. Among patients for whom quantitative futility applied, residents' predictions of the probability that patients would survive to hospital discharge after CPR varied from 0% (for 60% of patients) to 75%. For 32% of these patients, residents predicted survival at 5% or more. Logistic regression modeling showed that the presence of organ failure (odds ratio [OR], 8.9; 95% confidence interval [CI], 3.3 to 23.9), the residents' estimates of the probability of surviving CPR (OR, 0.94; 95% CI, 0.88 to 0.99), and nonwhite race (OR, 2.7; 95% CI, 1.1 to 6.3) were associated with the determination of quantitative futility. In one third of the cases where qualitative futility applied, residents made the judgment of qualitative futility without discussing quality of life with communicative patients. Logistic regression modeling showed immobility (OR, 3.2; 95% CI, 1.1 to 9.0) and age > or = 75 years (OR, 0.3; 95% CI, 0.1 to 0.8) to be associated with the determination of qualitative futility. CONCLUSIONS: While residents did not appear to use the medical futility rationale to avoid discussing DNAR issues with patients, we found evidence of important misunderstandings of the concepts of both quantitative and qualitative futility. If the futility rationale is to be applied to withholding or withdrawing medical interventions, practice guidelines for its use should be developed, and education about medical futility must be incorporated into medical school, residency training, and continuing medical education programs. PMID- 7799493 TI - Quality-of-life outcomes in men treated for localized prostate cancer. AB - OBJECTIVE: To assess health-related quality of life (HRQOL) in men treated for clinically localized prostate cancer. DESIGN: A cross-sectional analysis of HRQOL after treatment with radical prostatectomy, pelvic irradiation, or observation alone for clinically localized prostatic adenocarcinoma, and in age-matched comparison patients. SETTING: A large managed care population in California. SUBJECTS: A total of 528 men, including 214 treated for clinically localized prostate cancer (41 with evidence of metastatic disease were excluded from this analysis) and 273 age-matched, ZIP code-matched comparison patients without prostate cancer. Cancer patients were analyzed in three treatment groups: radical prostatectomy (n = 98), primary pelvic irradiation (n = 56), and observation alone (n = 60). MAIN OUTCOME MEASURES: General HRQOL was measured with the RAND 36-Item Health Survey 1.0. Cancer-specific HRQOL was measured with the CAncer Rehabilitation Evaluation System-Short Form and the Functional Assessment of Cancer Therapy-General form. Disease-targeted quality of life was measured with a new instrument assessing function and bother in three organ systems: sexual, urinary, and bowel. RESULTS: No differences among treatment groups were seen in comparisons of general HRQOL: Significant differences among treatment groups were seen in both function and bother in the prostate-targeted measures of sexual, urinary, and bowel domains. When cancer patients were compared with men of similar age without prostate cancer, differences were seen in the sexual, urinary, and bowel function and bother but not in general HRQOL measures. Although cancer-free men were found not to have full potency or continence, prostate cancer patients treated with surgery or radiation reported significantly worse sexual, urinary, and bowel function than men without cancer. Men who had undergone nerve-sparing prostatectomy did not differ from those who had undergone standard prostatectomy, but the power to detect a difference was low. CONCLUSIONS: Although no differences were seen in general HRQOL, three disease targeted domains were found to differ significantly among the treatment groups and comparison patients. Even after controlling for the sexual and urinary dysfunction experienced by older men without cancer, those receiving therapeutic interventions for their prostate cancer were found to have poorer disease targeted HRQOL: We conclude that in addition to general HRQOL, disease-targeted measures must be used to assess outcomes of care in men treated for localized prostate cancer. PMID- 7799494 TI - Risk stratification in unstable angina. Prospective validation of the Braunwald classification. AB - OBJECTIVES: To validate the Braunwald classification of unstable angina as a predictor of in-hospital cardiac complications; to determine which factors of the Braunwald classification contributed significantly to this prediction; and to devise a method of combining these predictive factors into an overall odds ratio for complications. DESIGN: A validation cohort of consecutive patients followed prospectively for in-hospital cardiac complications including myocardial infarction and death. SETTING: A community-based academic medical center. PATIENTS: A total of 393 patients admitted consecutively to the coronary care and intermediate care units with unstable angina. MAIN OUTCOME MEASURES: Major cardiac complications including death, myocardial infarction, congestive heart failure, cardiogenic shock, and severe ventricular dysrhythmias. RESULTS: Multiple logistic regression analysis identified four clinical factors used in the Braunwald classification that predicted the in-hospital occurrence of major cardiac complications: (1) myocardial infarction within less than 14 days (odds ratio [OR], 5.72; 95% confidence interval [CI], 1.92 to 16.97); (2) need for intravenous nitroglycerin (OR, 2.33; 95% CI, 1.31 to 4.17); (3) lack of beta blocker or calcium channel blocker prior to admission (OR, 3.83; 95% CI, 1.55 to 9.42); and (4) baseline ST depression (OR, 2.81; 95% CI, 1.45 to 5.47). Two other clinical factors, diabetes and age, were also significant predictors. Validation of this model using parametric and nonparametric bootstrap techniques revealed excellent agreement between the CIs for adjusted ORs derived from the multiple logistic regression and those derived from the bootstrap. CONCLUSIONS: The classification of unstable angina proposed by Braunwald includes four factors that predict risk of major in-hospital cardiac complications. Specific factors used in this classification can be combined with diabetes and age to better stratify risk of major cardiac complications in this disorder using a simpler model. PMID- 7799495 TI - Benefits and costs of screening and treatment for early breast cancer. Development of a basic benefit package. AB - OBJECTIVE: To develop a basic benefit package for detection and treatment of early breast cancer by evaluating the effectiveness and costs for screening mammography, primary surgery, adjuvant therapy, and follow-up care. DATA SOURCES: Published articles were retrieved through MEDLINE; additional articles were obtained through searches of their bibliographies. Cancer statistics were taken from Surveillance, Epidemiology, and End Results (SEER) Program data, population statistics were taken from US Census data, and charges from 1993 Southern California Medicare fees were used to represent costs. STUDY SELECTION: Studies were selected on the basis of their design. Preference, in decreasing order, was given to meta-analyses of randomized trials, individual randomized clinical trials, prospective cohort studies, retrospective cohort studies, and case series. DATA EXTRACTION: Studies were examined for the effect of the intervention on overall survival, disease-free survival, and health-related quality of life. We evaluated effects on survival in terms of number of lives saved at 10 years and average years of life saved. Costs were related to the benefits observed and modeled onto a hypothetical health care organization of 500,000 lives. RESULTS: Based on this analysis, we recommend a basic benefit plan for the detection and treatment of early breast cancer that would include the following: (1) screening mammography only for women aged 50 to 69 years; (2) choice of mastectomy or breast-conserving surgery with radiation therapy for all women with early breast cancer; (3) adjuvant therapy for all women at risk of recurrence; and (4) only clinical follow-up without routine testing for metastatic disease. CONCLUSIONS: By choosing which services they provide to specific groups of patients, providers can substantially reduce their expenses and still provide quality health benefits. PMID- 7799496 TI - Efficacy of screening mammography. A meta-analysis. AB - OBJECTIVE: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up. DESIGN: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects. MAIN RESULTS: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up. CONCLUSION: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age. PMID- 7799497 TI - Sepsis, sepsis syndrome, and the systemic inflammatory response syndrome (SIRS). Gulliver in Laputa. PMID- 7799498 TI - The organization of health care. PMID- 7799499 TI - Prognosis, diagnosis, or who knows? Time to learn what gene tests mean. PMID- 7799500 TI - Memories remain of Rwandan medical mission. PMID- 7799501 TI - Hearing elicits no plan to raise autopsy rates. PMID- 7799502 TI - Feds may fund study of existing embryos only. PMID- 7799503 TI - New program to SCOPE out resistant organisms. PMID- 7799505 TI - The polymerase chain reaction--expectations and realities. PMID- 7799507 TI - Peculiar histopathological features of giardiasis in distal duodenal biopsies. AB - Histological changes in 20 Giardia positive duodenal biopsies (Group A) were compared with 50, Giardia negative duodenal biopsies (Group B), taken during the same period. Stool examinations in Group B were negative for Giardia. Surface epithelium, villous and crypt architecture and cellular infiltrates were examined and compared between the groups. Atrophic changes in the villi were more common in Group A as compared to B(P < 0.0001). Intraepithelial neutrophil infiltration (P < 0.001), infiltration of the lamina propria with plasma cells (P < 0.5), and presence of eosinophils in the lamina propria (P < 0.001) were significant findings in group A. Some of the changes were related to the density of Giardia colonization e.g., the goblet cell depletion (P < 0.05) and the density of plasma cell infiltration in lamina propria (P < 0.01). Erosions and ulcerations were less commonly seen in group A. Thus we conclude that giardiasis manifests its peculiar features in the distal duodenal mucosa and a biopsy of this region is an important diagnostic tool for detection of this disease. PMID- 7799504 TI - From the Joint Commission on Accreditation of Healthcare Organizations. PMID- 7799508 TI - The effects of cigarette smoking on human gingival tissues (a histopathological study). AB - Gingival biopsy specimens were obtained from 9 smokers and 7 non-smokers during routine flap surgical procedure to investigate the effects of cigarette smoking on gingival epithelium and connective tissue. Although no remarkable histopathological difference was noted between gingival tissues of smokers and non-smokers, but smokers revealed relatively more epithelial keratosis, inflammatory cells, blood vessels and collagen fibres in connective tissue. Congestion of the capillaries were also more prominent in the smoker's gingival tissues. PMID- 7799506 TI - Pattern of malignant bone tumour in northern areas of Pakistan. AB - A review of 280 primary malignant bone tumours diagnosed during 1984-1988 is presented. These constituted 3.14% of all malignant tumours. Male to female ratio was 2.3:1. Majority of these patients presented with rapidly growing mass, pain and deformity. Histologically, osteosarcoma was the most frequent (36.4%) primary malignant tumour. Male to female ratio was 3.31:1. More than 49% of these cases were in their second decade of life. In females the greatest frequency was in 10 15 years and in males 16-20 years age groups. Femur was the most frequent site. Other common malignant bone tumours included chondrosarcoma (22.1%), plasma cell myeloma (15.0%) and Ewings's sarcoma (8.6%). Miscellaneous cases of fibrosarcoma, chrodoma, adamentinoma and ameloblastoma were also seen. This study outlines the frequency, symptomatology and histological pattern of various malignant bone tumours in northern areas of Pakistan. PMID- 7799509 TI - Role of diet on the enterohepatic recycling of estrogen in women taking contraceptive pills. AB - The effect of diet on the enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol (E3) was studied in six women using contraceptive pills. The women were followed for two consecutive menstrual cycles, firstly on a high fibre diet (HFD) and then changing on to low fibre diet (LFD) during the next cycle, hence each subject acted as its own control. The extent of enterohepatic recycling of estriol (E3) during the early follicular phase of menstrual cycle was assessed by monitoring during 48 hours, the urinary excretion of its two major metabolites, i.e., estriol-3-qlucuronide (E3-3-G) and estriol 16 alpha-glucuronide (E3-16 alpha-G). An increase in values of the variables including E3-3-G/E3-16 alpha-G output ratio, E3-3-G output as % of total (E3-3-G+E3-16 alpha-G) excretion and total E3 (E3-3-G+E3-16 alpha-G) output as % dose was noted as a result of change from high to low fibre diet. The urinary excretion of E3 in the form of its metabolites was also delayed as a result of dietary change. These findings reveal that extent of enterohepatic recycling of estrogen containing contraceptives could be higher in women on LFD as compared to those who are on HFD. PMID- 7799510 TI - The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the spontaneously beating isolated auricles of the rabbit heart. AB - The effects of NSAIDs (aspirin and indomethacin) on the isolated auricles of the rabbit heart were studied by observing the effects of these drugs on automaticity, excitability and contractility of the auricles. Aspirin (25,50,100 uM) produced concentration dependent depression in the automaticity of the SA node while indomethacin (10 uM, 25 uM) has stimulant effects and 50 uM produced depressant action. Only low concentration of indomethacin (10 uM) produced significant effect. Aspirin (25,50,100 uM) and indomethacin (50 uM) have significant depressant effects on the excitability of the auricles. Aspirin (100 uM) has suppressant effects (p < 0.05) on the normal contractility while the adrenaline stimulated contractility is not suppressed by aspirin and indomethacin significantly. The results obtained in this study with aspirin and indomethacin on chronotropicity and inotropicity of the rabbit atria have been discussed in the light of experimental work done by the workers regarding conventional antiarrhythmic drugs. PMID- 7799511 TI - A concentration technique for obtaining viable cysts of blastocystis hominis from faeces. PMID- 7799512 TI - Association between education and health-household survey of Faisalabad Tehsil. PMID- 7799513 TI - Amineptine dependence. PMID- 7799514 TI - Dysplasia and surveillance in ulcerative colitis. PMID- 7799515 TI - Prevalence of hepatitis B infection in professional and family/voluntary blood donors. PMID- 7799516 TI - Prevalence of HB infection in haemodialysis patients. PMID- 7799517 TI - Administration time-dependent change in the effect of spironolactone in rats. AB - The present study was undertaken to examine whether the natriuretic effect of spironolactone, a competitive antagonist of mineralocorticoid, varies with its time of administration. Wistar rat maintained under the condition of light from 7 hr to 19 hr were divided into two groups. The first group had a bilateral adrenalectomy and received a 50-mg deoxycorticosterone acetate (DOCA) tablet intraperitoneally (DOCA group). The second group had a sham operation (control group). Spironolactone (50 mg/kg) was given orally at 12 hr or 24 hr, and the 8 hr urine was collected. At the end of the experiment, the blood sample for measurement of aldosterone was obtained at 12 hr and 24 hr in the control group. The natriuretic effect of spironolactone in the 24 hr-trial was significantly greater than that of the 12 hr-trial in the control group. However, such a time dependent difference was diminished and did not reach statistical significance in the DOCA group. The plasma aldosterone concentration at 24 hr was significantly higher than that at 12 hr in the control group. These results suggest that the natriuretic effect of spironolactone varies with its time of administration. Daily variation in mineralocorticoid activity might be involved in this chronopharmacological phenomenon of spironolactone. PMID- 7799519 TI - Effects of NS-2, a new class 1 antiarrhythmic agent, and AFD-19, its active metabolite, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats: comparison with disopyramide and mexiletine. AB - We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino-1,1-diphenyl-1 butanol maleate) and AFD-19 (active metabolite of NS-2) on early stage ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized male rats. These effects were compared with those of disopyramide and mexiletine. Drugs were intravenously administered either before or after coronary occlusion. When administered 5 min before occlusion, 3 mg/kg of NS-2 and AFD-19 exhibited equivalent anti-arrhythmic activity to that of 5 mg/kg of disopyramide and mexiletine, as assessed by reductions in the number of premature ventricular complexes and in the incidences of ventricular tachycardia and ventricular fibrillation. In a dose of 5 mg/kg, the antiarrhythmic effects of NS 2 and AFD-19 were more pronounced. When administered 5 min after coronary artery occlusion, only NS-2 and AFD-19 (in doses of 5 mg/kg) had significant antiarrhythmic effects. None of the drugs influenced the severe ventricular arrhythmias induced by reperfusion when administered 1 min before reperfusion. In conclusion, NS-2 might be effective in reducing the severity of the life threatening ventricular arrhythmias that occur during acute myocardial infarction. PMID- 7799518 TI - K(+)-linked release of oxidized glutathione induced by tert-butyl hydroperoxide in perfused rat liver is independent of lipid peroxidation and cell death. AB - The tert-butyl hydroperoxide (BHP)-induced release of oxidized glutathione (GSSG) and K+ was studied in relation to lipid peroxidation and cell death using isolated perfused rat livers. Infusion of BHP into the perfused liver resulted in an early and simultaneous release of GSSG and K+ and a sustained release of thiobarbituric-acid-reactive substances (TBARS) into the effluent perfusate, which was followed by further prenecrotic leakage of K+ followed by lactic dehydrogenase (LDH). These actions of BHP were not significantly affected by cutting or ligating the bile duct, and they were potentiated by omitting Ca2+ from the perfusion medium. Co-infusion of desferrioxamine, propyl gallate and diethyldithiocarbamate suppressed TBARS release as well as the later leakage of K+ and LDH. Desferrioxamine was also effective under Ca(2+)-free conditions. N,N' diphenyl-p-phenylenediamine inhibited TBARS release, but it was not protective against cell death, although there was some delay. The action of dithiothreitol was only moderate. On the other hand, leakage of TBARS, K+ (prenecrotic) and LDH was enhanced by cysteamine and beta-mercaptoethanol and most markedly enhanced by ferrous iron. However, none of these agents markedly affected the early release of GSSG and K+. These observations, which support our previous findings, suggest that the early and coupled sinusoidal efflux of GSSG and K+ caused by BHP is independent of lipid peroxidation and cell death and that they represent a physiological mechanism of GSSG release. The results also suggest that lipid peroxidation is not the sole cause of BHP-induced cell death. PMID- 7799520 TI - Ca2+ inactivation of voltage-dependent Na+ channels in cultured bovine adrenal chromaffin cells: further studies on inhibition of veratridine-induced catecholamine secretion by external Ca2+. AB - The stimulatory actions of veratridine (VTD) on catecholamine secretion and Na+ influx in cultured bovine adrenal chromaffin cells were studied in the presence of high concentrations of Ca2+ in the incubation mixture. Catecholamine secretion evoked by VTD was reduced by elevating the external Ca2+ concentration to higher than 2 mM. Under the same conditions, VTD-stimulated 22Na+ uptake into the cells was also reduced by elevating the extracellular Ca2+ concentration. In contrast, the secretory action of VTD was not significantly suppressed by preloading Ca2+ to the cells. Furthermore, the effects of extracellular Ca2+ on the sensitivities of the cells to VTD and tetrodotoxin (TTX) were examined, and neither their sensitivities to VTD nor those to TTX were shown to be significantly altered by elevating the Ca2+ concentration in the incubation mixture. These results seem to indicate that the elevation of extracellular Ca2+ concentration may cause the inhibition of VTD-induced catecholamine secretion as a consequence of the inactivation of voltage-dependent Na+ channels, and suggest that Ca2+ may directly act on the cell surface, and the site of Ca2+ action is presumably distinct from the sites of both VTD and TTX actions in the plasma membranes of adrenal chromaffin cells. PMID- 7799521 TI - Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation. AB - Antioxidative effects of the nitrovasodilator nicorandil (SG-75) and denitrated SG-75 (SG-86) were examined in vivo and in vitro. When the isolated rat liver was reperfused with Krebs-Henseleit solution after a 90-min ischemia, microsomal GSH S-transferase activity was increased significantly by oxidative modification of the sulfhydryl group of the enzyme. The increase in the transferase activity after ischemia/reperfusion was depressed by SG-75 but not by SG-86. Furthermore, only SG-75 significantly inhibited lipid peroxidation and the activation of microsomal GSH S-transferase induced by hydrogen peroxide treatment of liver microsomes. These data indicate that SG-75 has an antioxidative action and the nitro group of SG-75 may play a critical role for this action. PMID- 7799523 TI - The effects of dobutamine, propranolol and nitroglycerin on an experimental canine model of congestive heart failure. AB - A new experimental model of acute congestive heart failure was established in open-chest dogs, and it was employed to examine the effects of dobutamine, propranolol and nitroglycerin. The model was induced by intracoronary administration of saponin, volume loading and intravenous infusion of methoxamine. Left ventricular end-diastolic pressure (LVEDP) increased from 7.9 +/- 0.6 to 24.2 +/- 1.4 mmHg, and aortic blood flow (AoF) decreased from 0.89 +/- 0.06 to 0.53 +/- 0.04 l/min. Systemic vascular resistance (SVR) increased from 9618 +/- 585 to 16492 +/- 1213 dynes.sec/cm5 and right atrial pressure (RAP) increased from 2.5 +/- 0.2 to 4.2 +/- 0.4 mmHg. Furthermore, Vmax decreased from 71.6 +/- 5.1 to 45.8 +/- 2.9 1/sec, and the time constant of left ventricular pressure decay (T) increased from 40.0 +/- 2.6 to 90.2 +/- 7.9 msec. These hemodynamic changes were stable for up to 80 min. Dobutamine improved cardiac function by increasing Vmax and by decreasing T. Consequently, dobutamine increased AoF and decreased LVEDP, while there was no change in SVR. Nitroglycerin reduced LVEDP, SVR and T; increased AoF; and did not change Vmax. Propranolol produced no improvement in the hemodynamics or cardiac function. These results indicate that the present congestive heart failure model is characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and it is beneficial for evaluating the pharmacological properties of drugs for acute congestive heart failure. PMID- 7799522 TI - Effects of glibenclamide on negative cardiac responses to cholinergic and purinergic stimuli and cromakalim in the isolated dog heart. AB - We investigated the effects of an ATP-sensitive K+ channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetylcholine (ACh, a muscarinic receptor agonist), ATP (a P2-purinergic receptor agonist), adenosine (a P1 purinergic receptor agonist) and cromakalim (a potassium channel opener) in the isolated, blood-perfused canine right atrium of left ventricle. A high dose of glibenclamide (3 mumol) did not affect the negative chronotropic and inotropic responses to parasympathetic stimulation (frequencies of 1-30 Hz), although it slightly but significantly attenuated the negative cardiac responses to exogenous ACh (0.3-10 nmol). Furthermore, adenosine (0.03-0.3 mumol)-induced negative chronotropic and inotropic responses were significantly inhibited by glibenclamide (3 mumol), but ATP (0.01-1 mumol)-induced negative cardiac responses were not affected. A cumulative administration of cromakalim (0.01-1 mumol) dose-dependently caused much greater decreases in the contractile force of atrial and ventricular muscles than in sinus rate. Glibenclamide (0.3-3 mumol) similarly blocked the negative chronotropic and inotropic responses to cromakalim in a dose-dependent manner. These results suggest that glibenclamide modifies the negative cardiac responses to parasympathetic activation both in pre- and postjunctional sites and the responses to adenosine but not to ATP at K+ channels in the dog heart, although the modifications are minor under physiological conditions. PMID- 7799524 TI - Serotonin (5-HT)3-receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives against 5-HT-induced bradycardia in anesthetized rats. AB - We investigated the mode of the 5-HT3-receptor antagonism of 4,5,6,7 tetrahydrobenzimidazole derivatives, YM060, YM114 (KAE-393), YM-26103-2 and YM 26308-2, against 5-HT-induced transient bradycardia in anesthetized rats. Results were compared with those of ondansetron and granisetron. YM060 (0.03-0.1 microgram/kg, i.v.), YM114 (0.03-0.3 microgram/kg, i.v.), YM-26103-2 (0.01-0.03 microgram/kg, i.v.), YM-26308-2 (0.01-0.03 microgram/kg, i.v.) and granisetron (0.3-3 micrograms/kg, i.v.) displaced the 5-HT dose-response curve to the right, with apparent DR2 values of 0.068, 0.068, 0.019, 0.011 and 0.69 microgram/kg, i.v., respectively. Higher doses of these compounds inhibited 5-HT-induced bradycardia with a reduced maximal response. In contrast, ondansetron displaced the 5-HT dose-response curve to the right without affecting the maximal response. Judged by the apparent DR2 values, YM060, YM114, YM-26103-2 and YM-26308-2 were approximately 13, 13, 50 and 79 times more potent than ondansetron, respectively, whereas granisetron was equipotent to ondansetron. Single i.v. doses of YM060 and granisetron inhibited 5-HT-induced bradycardia significantly longer than ondansetron. Moreover, inhibitory effects of p.o. doses of YM060 (3 micrograms/kg), YM114 (80 micrograms/kg), YM-26103-2 (12 micrograms/kg), YM-26308 2 (5 micrograms/kg) and granisetron (250 micrograms/kg) on the von Bezold-Jarisch reflex lasted for 3-6 hr, whereas ondansetron (700 micrograms/kg, p.o.) antagonized 5-HT3 receptors for only 1 hr. In isolated guinea pig colon, the inhibitory effect of YM-compounds on 5-HT-induced contraction persisted significantly longer than those of ondansetron and granisetron after washout of the bath containing compounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799525 TI - Effect of trimebutine on contractile responses in skinned ileal smooth muscle. AB - The effects of trimebutine on Ca2+ release and modulation of Ca2+ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 microM) concentration dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) in potentiating Ca2+ sensitivity of the contractile elements after the Ca2+ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca2+ release by acting at some point during the coupling of muscarinic receptors through a G protein to phospholipase C and thus reducing the accumulation of IP3. PMID- 7799526 TI - Thrombolysis of canine femoral artery thrombus by a novel modified tissue-type plasminogen activator (E6010). AB - The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper coil-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of various thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E6010 was identical to that of continuous intravenous infusion of recombinant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic agents. On the other hand, administration of the thrombolytic agents dose-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with administration of E6010, and therefore we concluded that E6010 is unlikely to cause bleeding complications after administration. PMID- 7799527 TI - Characterization of 5-hydroxytryptamine receptors on the isolated pig basilar artery by functional and radioligand binding studies. AB - 5-Hydroxytryptamine (5-HT)-receptor subtypes on pig basilar arteries were investigated by measuring the contractile responses to 5-HT agonists, the effects of antagonists on the responses and by carrying out a radioligand binding assay with [3H]5-HT. The rank order of contractile agonist potency (according to the pEC50 values) was 5-carboxamidotryptamine > or = 5-HT > alpha-methyl-5-HT > (+/-) 8-hydroxy-dipropylaminotetralin. The contractile responses were not affected by endothelial denudation, and the 5-HT-induced contractions were antagonized competitively by ketanserin. Methiothepin shifted the 5-HT concentration-response curves to the right and downwards in a concentration-dependent manner. In the presence of ketanserin (10(-6) M), however, methiothepin antagonized the 5-HT induced contractions competitively. Specific [3H]5-HT binding to 5-HT receptors was saturable, reversible and showed high (Kd, 2.5 nM) and low (Kd, 710 nM) affinities, with respective Bmax values of 29.5 and 1950 fmol/mg protein. These results indicate that both 5-HT1 and 5-HT2 receptors are present on pig basilar arterial smooth muscle cells, and their stimulation results in contraction. PMID- 7799528 TI - The mechanism of muscarinic agonist-stimulated inositol phosphate formation in permeabilized ileal smooth muscle. AB - Muscarinic agonists and guanylyl-5'-imidodiphosphate (Gpp(NH)p) stimulated formation of inositol phosphates in permeabilized longitudinal smooth muscle of guinea pig ileum. Gpp(NH)p markedly potentiated the formation of inositol bisphosphate (IP2) and inositol trisphosphate (IP3) stimulated by carbachol, but increased inositol monophosphate formation (IP1) only slightly. Gpp(NH)p enhanced the formation of IP2 + IP3 induced by either acetylcholine or carbachol about fourfold in a synergistic manner, but enhanced the effects of oxotremorine and pilocarpine less than twofold in an additive manner. Elevation of Ca2+ concentration resulted in increases of the inositol phosphate levels stimulated by both carbachol and Gpp(NH)p. The optimal concentration of Ca2+ for carbachol stimulated formations of IP2 + IP3 was shifted to a lower Ca2+ concentration in the presence of Gpp(NH)p. These findings suggest that muscarinic receptor stimulated polyphosphoinositide hydrolysis in ileal smooth muscle results in inositol polyphosphate formation via GTP binding protein (G-protein). The muscarinic receptor-activated G-protein decreases the Ca2+ requirement of polyphosphoinositide hydrolysis. Muscarinic agonists stimulate inositol polyphosphate formation by interaction of the G-protein activation of a phosphoinositide specific phospholipase C with Ca2+ influx. PMID- 7799529 TI - Spasmolytic effect of the NK2-receptor-selective antagonist MEN 10,627 in rat small intestine. AB - The effect of activation of tachykinin NK2-receptors on gastrointestinal propulsion was studied in vivo in conscious rats. The selective NK2-receptor agonist [beta Ala8]NKA-(4-10) produced an atropine-resistant specific increase of the small intestinal transit measured by the charcoal method. This effect was restricted to the small intestine since gastric emptying was not affected by [beta Ala8]NKA-(4-10). The newly developed polycyclic peptide NK2-receptor antagonist MEN 10,627 produced a dose-dependent inhibition of this stimulated transit. The spasmolytic effect of MEN 10,627 was highly selective because it did not affect stimulated intestinal transit induced by equieffective doses of carbachol and reserpine. These findings indicate that MEN 10,627 is a valuable tool for assessing the role of NK2-receptors in intestinal propulsive activity. PMID- 7799530 TI - Anticancer effects of adriamycin-loaded hydroxyapatite implants determined in a Swarm rat chondrosarcoma model. AB - We investigated the antitumor effects of adriamycin (ADR)-loaded hydroxyapatite (HAP) beads in a Swarm rat chondrosarcoma model. When one ADR-loaded HAP bead (ADR: 0.8 mg/bead) was implanted into the central portion of a rat bearing tumor, the ADR-loaded HAP beads showed good therapeutic effects, increasing the life span (ILS) by 90%. Significantly, leukopenia and diarrhea were not observed. These results suggest that HAP delivery offers an interesting and a potentially effective method. PMID- 7799531 TI - Inhibitory effects of 7-OH-DPAT, dopamine D3-receptor agonist, on nucleus accumbens neurons. AB - Effects of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine D3 receptor agonist, on neuronal activities of the nucleus accumbens (Acc) were examined in chloral hydrate-anesthetized rats. Spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by microiontophoretic application of dopamine and 7-OH-DPAT. Glutamate-induced firing was also inhibited by these drugs. These findings suggest that D3 receptors are also involved in the postsynaptic inhibition of Acc neuron by dopamine. PMID- 7799532 TI - Law and ethics in psychiatry. Proceedings of the 8th Tokyo Institute of Psychiatry International Symposium. Tokyo, November 17-18, 1993. PMID- 7799533 TI - Criminal responsibility in amphetamine psychosis. AB - Historical changes in forensic psychiatric evaluation on criminal responsibility and proceedings in psychopathological findings of amphetamine psychosis are reviewed at first. The classification of amphetamine related mental disorders are proposed in 6 types. Among them, the clinical characteristics and psychopathological features of "Anxiety-situational reaction type" (Fukushima) are described. According to some reasonable grounds, offenders diagnosed as anxiety-situational reaction type should be evaluated as diminished responsibility in place of irresponsibility. Finally, two cases of murder committed under the influence of amphetamine, are reported in detail. PMID- 7799534 TI - Reform of mental health laws: not repeating the mistakes made in the United States. PMID- 7799535 TI - The Mental Health Act 1983 for England and Wales: contemporary issues and proposals for reform ten years on. PMID- 7799536 TI - Reform of "hogosha" system and psychiatric practice in Japan. AB - In this paper, the author examines the current working and drawbacks of the "hogosha" system as set out in the Mental Health Law of 1988, and goes on to suggest a plan for reform. Critics point to two main problems with the current system. One is that the hogosha's powers infringe on the patient's human rights. The other is that the system places too heavy a burden on hogoshas in its efforts to protect the community from the patient. The author argues that the hogosha should retain the power to consent for admission for medical care and custody, but other responsibilities should be reduced. The author stresses that local mayors must be prepared to take their responsibilities seriously when they assume the role of the hogosha. PMID- 7799537 TI - Reform in French legislation concerning psychiatric hospitalization 1838-1990. PMID- 7799538 TI - Criminal policy for offenders with mental disorder in Japan. PMID- 7799539 TI - Competence and responsibility in schizophrenia. AB - In a survey of the historical background it is shown that the classical doctrine on responsibility in schizophrenia has left its mark on the wordings of the psychiatric textbooks of the different countries. Closely combined with the imputation of enduring irresponsibility in schizophrenia was the opinion that civil rights are largely suspended if a person is given the diagnosis of schizophrenia. By the more recent research results of the studies of course and long-term outcome of schizophrenia and related psychoses and the development of the basic symptom concept has shown that it is not justified on principle to summarily deprive a person, diagnosed as schizophrenia, of civil rights as well as of criminal responsibility. New directions and some guidelines for an adequate assessment of competence and responsibility in schizophrenia are described. The knowledge of the newer findings and the application and utilization of the concept of basic symptoms and non-psychotic basic stages enable to overcome the doctrines of incurability, principle heterogeneity and numinous singularity and may lead to a rather appropriate and adequate social appreciation of the disease. Insight, freedom, responsibility, and competence of a person diagnosed as schizophrenia are in the postpsychotic pure residues and basic stages much more frequently preserved and available than hitherto assumed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799540 TI - Ethical issues in psychotherapy. AB - The goal of psychotherapy is not only the dissolution of the symptoms, but also to attempt to bring about an improvement in adaptability and deepening the achievement of self-understanding. The nature of psychotherapy is based on the relationship between the therapist and patient. Such a goal and nature mean that some kinds of psychotherapy are beyond the medical model. In this paper ethical issues in psychotherapy are discussed as follows. 1) some complicated matters in informed-consent, 2) the hit or miss techniques of the poorly trained therapist, 3) the protection of privacy, 4) the sexual misconduct of therapists with patients, 5) special consideration for child-adolescent patients. PMID- 7799541 TI - Ethical issues in sexual misconduct by clinicians. AB - Sexual misconduct by clinicians in the form of sexual relations with patients has long been recognized as an ethics violation and an activity suitable for assessment by the ethics committees of institutions and local and national professional organizations. The issue can be examined from the vantage point of several types of duties which bear ethical implications; these ethical duties proceed from the following four notions in this area: Sexual misconduct represents a violation of professional ethics as a fiduciary breach, abuse of a power asymmetry, exploitation of vulnerability and use of undue influence. While objections to these criteria may be raised in terms of freedom of association and consent, the violation of ethical principles by sexual misconduct remains clear. PMID- 7799542 TI - The patient as "subject" and capacity to give informed consent. AB - In line with Western countries, the idea of "capacity assessment" to determine a person's course of treatment is being introduced to Japanese psychiatry. Herein, some problems associated with the informed consent of mental patients are discussed, and a typical case is presented. The author points out that, when involuntary treatment is necessary, the clinician must consider, 1) the self as a "subject" of the incapable, 2) the dissociation between a subject and a choice, 3) the nature of choice in life, 4) contextual assessment of mental intervention in the patient's life situation. Neglecting these issues will lead to inhumane medical practice in psychiatry. PMID- 7799543 TI - Personality disorders: conceptual issues and responsibility. AB - The historical roots of the concepts of abnormal personality, social deviance, delinquency and penal responsibility are described, demonstrating that former concepts of psychopathic personality often included negative social evaluations. Modern classification systems such as DSM-III-R and ICD-10 prefer a behavior oriented definition of personality disorders, which increases reliability but may lead to a reductionistic and purely criteriological assessment of personality. A checklist for the assessment of personality disorders (AMPS) according to ICD-10 and DSM-III-R is presented, including four subaffective forms derived from the typology of personality disorders described by Kurt Schneider and Kretschmer. To justify statements of diminished legal responsibility or irresponsibility under the German Penal Code, a differentiation between psychopathological phenomena in personality disorders and pure social deviance is needed. The three notions of psychopathy, sociopathy and dissocial behavior are suggested to guide necessary decisions concerning prognosis and therapy chances. PMID- 7799544 TI - Ethical problems in psychiatric everyday practice. AB - For the ethical evaluation of psychiatric decisions the will of the patient- apart from his welfare, of course--has gained special importance in recent years. It is constitutionally protected in the form of self-determination. Accordingly the physician can only act with the patient's consent. The capacity of the individual to consent may be impaired or suspended because of a mental disease. It is often difficult, however, to recognize this impairment, to assess its extent, to evaluate its current relevance and to draw the correct conclusions. This becomes important when the psychiatrist deals with a patient whose will is in opposition to his welfare. Difficulties for the physician may also result because his therapy, regardless of whether it is somatic therapy or psychotherapy or involves social measures, though aiming to remove the mental disturbance and with the ultimate objective of the patient regaining his lost autonomy in mind, may at times curtail the self-determination of the patient. These difficulties are illustrated by some examples with the objective to maintain our awareness of these issues in our everyday work. PMID- 7799545 TI - Ethical issues in criminal forensic evaluation. AB - Psychiatric practices have been widely intervened by third parties, so that absolute confidentiality cannot be demanded. Forensic psychiatry holds a distinctive position in such practices. Ethics in forensic evaluations rely on the role of the psychiatrist. That role must be provided not only within the relationship with the truster, but also with the evaluee. The latter relationship has seldom been discussed. It is not therapist-patient-relationship, leaving some therapist attitude. A warning (lack of confidentiality, etc.) is necessary before the evaluation. Despite all, psychiatric evaluations cannot be conducted without some reliance. It is important to inform the evaluee of the evaluator's opinion prior to the trial, and involve the evaluee in the process of the evaluator's recognition. PMID- 7799546 TI - Treating the mentally disordered criminal offender in a hospital setting. AB - The author outlines the legislation and treatment system for mentally disordered criminal offenders in Japan, and reviews the recent studies on the treatment of refractory patients in mental hospitals. Involuntary admission of patients referred by a public prosecutor or by a head of a correctional institution is problematic regarding the judgment criteria for admission and discharge, and imposes a burden on practitioners. The author outlines the main problems of the treatment of criminal offenders in a hospital setting: reaction to the hospital environment, lack of motivation for treatment, therapists' reluctance to treat these patients, absence of support for rehabilitation and uncertainty about future risk. Suggested measures for the solution of these difficulties include the role of the Psychiatric Review Board, the psychiatric evaluation system, and therapeutic skills pertaining to dangerous patients. PMID- 7799547 TI - New directions in the assessment of dangerousness of the mentally ill. PMID- 7799549 TI - Forensic psychiatry in England: a system in transition. PMID- 7799548 TI - The treatment of mentally disordered offenders in Japanese medical prisons. AB - The author outlines the general trends of crime and the treatment of criminals in Japan, and trends of mentally disordered offenders in Japanese penal institutions. Further, he explains the treatment of the mentally disordered offenders in Japanese medical prisons. The author analyzes the Hachioji Medical Prison's treatment record, particularly in regards to the reincarceration rate, which markedly decreases when family support and psychiatric treatment are properly present after release. Finally, the author stresses the value of correctional psychiatric treatment in the medical prison; it is expected to play an important role in contributing to the rehabilitation of mentally disordered offenders and "patients difficult to treat," and bringing about more open and innovative community-centered mental health services. PMID- 7799550 TI - [Argyrophilic proteins of nucleolar organizer regions of macrophages and lymphocytes in bronchoalveolar lavage fluid from patients with diffuse lung diseases]. AB - Alveolar macrophages and T-lymphocytes in bronchoalveolar lavage fluid from patients with diffuse lung diseases have been shown to be activated. The object of this study was to investigate whether the numbers of nucleolar organizer regions (NORs) in alveolar macrophages and lymphocytes were abnormally high in these patients or not. Alveolar macrophages and lymphocytes were collected by bronchoalveolar lavage from 7 control subjects, 36 patients with pulmonary sarcoidosis, 10 patients with hypersensitivity pneumonitis, 6 patients with measles pneumonia, 6 patients with mycoplasma pneumonia, and 6 patients with progressive systemic sclerosis related to interstitial pneumonitis. These cells were cytocentrifuged and stained by one-step silver staining. Argyrophilic proteins of the nucleolar organizer regions (Ag-NORs) were counted in 300 alveolar macrophages and lymphocytes. The numbers found in control subjects were compared to those found in patients with diffuse lung diseases. In the patients with sarcoidosis, these numbers were also compared among subgroups divided according to staging, involvement of other organs, administration of steroids, and differences in deposition of 67Ga. We also examined correlations between Ag- NORs and known markers of activation in sarcoidosis. The numbers of Ag-NORs were significantly greater in patients with diffuse lung diseases than in control subjects. There were no significant differences in the numbers of Ag-NORs among subgroups of patients with sarcoidosis. No correlations were seen between the Ag NORs and the markers of activation of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799551 TI - [Bronchial hyperresponsiveness before and after percutaneous transluminal mitral commissurotomy in patients with mitral stenosis]. AB - To study the effects of percutaneous transluminal mitral commissurotomy (PTMC) on bronchial responsiveness to inhaled methacholine in patients with mitral valve stenosis (MS), methacholine inhalation tests and pulmonary function tests were done in 10 patients with MS before and one week after PTMC. The mean log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) was significantly higher after PTMC in nine patients in whom PTMC was successful (p < 0.05). There were no significant changes in the results of pulmonary function tests after PTMC. One patient had severe mitral regurgitation after PTMC, and a decrease in PD35Grs. Six of the other nine patients in whom PTMC was successful continued to be hyperresponsive to inhaled methacholine. These data show that bronchial hyperresponsiveness in patients with MS is less severe after PTMC, concomitant with the relief of pulmonary congestion, and they suggest that the remaining bronchial hyperresponsiveness is responsible for peripheral airway narrowing with organic remodeling. PMID- 7799552 TI - [Six cases of allergic bronchopulmonary aspergillosis]. AB - Six cases of allergic bronchopulmonary aspergillosis (ABPA) were evaluated. In four cases, diagnosis and steroid therapy were delayed, which resulted in irreversible pulmonary dysfunction. The important points for early diagnosis were: (1) Differentiation from pulmonary tuberculosis, (2) the presence of bronchial asthma was not essential for diagnosis, and (3) fungi other than Aspergillus fumigatus might cause this syndrome. PMID- 7799553 TI - [Mechanism of hypoxemia after methacholine challenge]. AB - Hypoxemia after the treatment of asthmatic attack continues for a while, and can even become worse after the treatment. This hypoxemia has been attributed to inhomogeneity of ventilation-to-perfusion ratios in the lungs of asthmatic patients. We studied post-hyperventilation hypoxemia in subjects with hypoxemia after a methacholine challenge test. Nineteen subjects who were hyperresponsive and hypoxemic after a methacholine challenge were studied. The methacholine challenge with incremental doses was stopped when the respiratory resistance doubled. Thereafter, oxygen and carbon dioxide concentrations in the expired air, mouth flow (VE), and oxygen saturation (using a pulse oximeter, SpO2) were monitored continuously. End-tidal PCO2 (PETCO2) as well as respiratory exchange ratio (R) were thus obtained. In 14 subjects, VE significantly increased from 8.6 +/- 1.2 (mean +/- SD) to 13.4 +/- 2.6 l/min and then decreased gradually, while PETCO2 significantly decreased from 38.5 +/- 2.3 to 29.1 +/- 4.4 Torr and then increased gradually, SpO2 decreased from 97 +/- 1.3 to 89 +/- 2.4% concomitant with a significant decrease in R from 0.86 +/- 0.04 to 0.67 +/- 0.05. In contrast, in 5 subjects VE significantly increased from 7.5 +/- 2.8 to 12.4 +/- 1.6 l/min and then remained unchanged, while PETCO2 significantly decreased from 37.9 +/- 1.3 to 31.3 +/- 3.9 Torr and then remained unchanged, SpO2 decreased from 98 +/- 1.1 to 92 +/- 1.9% with no change in R (from 0.84 +/- 0.06 to 0.87 +/ 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799554 TI - [Clinical bacteriology and empiric therapy for hospital-acquired pneumonia in the elderly at a national leprosarium]. AB - Hospital-acquired pneumonia is one of the most important fatal respiratory diseases in the elderly. Prompt and precise empiric therapy is essential for recovery. Fourteen isolates from twelve elderly lepromatous leprosy patients (9 men, 3 women, mean age of 75.8 years) with hospital-acquired pneumonia were studied. Subsequently, empiric therapy with gentamicin and beta-lactams for nosocomial pneumonia in the elderly was examined. Fourteen types of bacteria isolated from expectorated sputum specimens consisted mainly of ten strains of gram-negative bacilli (71%) six of Klebsiella pneumoniae, one each of Citrobacter freundii, Enterobacter agglomerans, Serratia liquefaciens, and Aeromonas hydrophilia and four strains of gram-positive cocci (29%) two of Staphylococcus sp., one each of Streptococcus sp. and Streptococcus pneumoniae. Methicillin resistant Staphylococcus aureus and Pseudomonas sp. were not detected. Resistance rates of the etiologic agents to the antibiotics showed that gentamicin was 7.7%, ceftazidime 0%, and cefmetazole 23.1%. Cephalosporins were superior to penicillins. As a result of empiric therapy, six elderly leprosy patients with nosocomial pneumonia were cured and one improved temporarily. This study shows the necessity of specific empiric therapy for hospital-acquired pneumonia in a hospital with many elderly patients. The combination of gentamicin and beta lactams is of value as an initial antibiotic therapy for hospital-acquired pneumonia in the elderly. PMID- 7799555 TI - [A case of Swyer-James syndrome--a morphological study with inflated fixed lung]. AB - Morphological features of Swyer-James syndrome were studied in a specimen obtained during left pneumonectomy. A 67-year-old woman was admitted because her left lung was hyperlucent and contained a solitary nodule. Primary lung adenocarcinoma complicated with Swyer-James syndrome was diagnosed, and left pneumonectomy done. The left upper lobe was inflated and fixed for morphological study. The volume of the specimen was obviously lower than normal but the bronchial branching was normal. Macroscopically, the specimen had irregular bronchial walls, bronchiectatic changes, and dilation of distal air spaces, similar to panlobular emphysema. Microscopically, there was scarring in periarteriolar regions that suggested bronchiolitis obliterans, enlargement of distal airspaces, and an abnormally low number of capillaries. These findings suggest hypoplasia of the lung due to abnormal lung growth after birth. PMID- 7799556 TI - [A case of interstitial pneumonitis caused by inhalation of cadmium fumes]. AB - A 48-year-old man who had been a welder for 25 years was admitted to our hospital on February 18, 1990 for investigation of a diffuse bilateral lung shadow that had a ground-glass appearance. On the day of admission, he had been welding copper water supply pipe and used silver brazing with an oxyacetylene torch. After almost 7 hours of work, he had a chill, high fever, and dyspnea. Blood gas analysis revealed severe hypoxemia (PaO2 34.5 Torr, PaCO2 29.4 Torr). The level of copper in serum was slightly higher than normal (174 micrograms/dl). A transbronchial lung biopsy specimen showed lymphocyte infiltration and fibrous changes of the alveolar walls, which seemed to be granulomatous pneumonitis. Steroid therapy was effective against the symptoms, and the radiographic findings also improved. We think this is a rare case of interstitial pneumonitis caused by inhalation of cadmium fumes contained in silver brazing. PMID- 7799557 TI - [Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression]. AB - A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression. PMID- 7799558 TI - [A case of Churg-Strauss syndrome associated with severe leg pain and necrotizing skin lesions]. AB - A 68-year-old woman with bronchial asthma and a history of drug hypersensitivity came to our hospital because of severe pain, swelling, and ecchymoses in the lower extremity. The eosinophil count was 53.5%, therefore Churg-Strauss syndrome was diagnosed and she was given prednisolone (PSL) (30 mg/day). A skin specimen taken the next day showed tissue eosinophilia, acute and subacute necrotizing vasculitis. Immunofluorescence staining showed IgG in the blood vessels. After one month of PSL, biopsy specimens of muscle fiber revealed atrophy of type IIb fibers, and myxomatous degeneration of neuron-fibers. Eosinophilia decreased rapidly after administration of PSL, but the necrotizing lesions of the skin, muscle, and nerve were so severe that she needed orthopedic shoes. PMID- 7799560 TI - [A case of aspirin-induced cough without bronchoconstriction. A new type of aspirin hypersensitivity]. AB - A 54-year-old woman was admitted to our hospital because of an asthmatic attack. Her first asthma attack occurred when she was 53 years old. It was followed by a flu-like infection, and was preceded for one year perennial rhinitis and loss of the sense of smell. Symptoms were perennial, and unrelated to the seasons. Because these clinical findings resembled those of aspirin-induced asthma (AIA), an aspirin-DL-lysine i.v. challenge test was done. Cough, perspiration, and flushing was provoked within 15 min after aspirin-DL-lysine injection, but FEV1 did not change. Respiratory sounds were normal and no wheezing was audible. Other cyclooxygenase inhibitors (ketoprofen, sulpyrine and acetaminophen) provoked the same symptoms. Successively increasing doses of injected aspirin-DL-lysine resulted in complete tolerance to this stimulus. We propose that aspirin-induced cough without bronchoconstriction is a new type of aspirin hypersensitivity. PMID- 7799559 TI - [A case of pulmonary alveolar proteinosis with elevated serum angiotensin converting enzyme activity]. AB - A 45-year-old man with diffuse infiltrates on the chest X-ray film was admitted to the hospital. At first, sarcoidosis was suspected due to the elevated serum angiotensin-converting enzyme (ACE) activity. Transbronchial lung biopsy and bronchoalveolar lavage, however, did not lead to that diagnosis. Pulmonary alveolar proteinosis (PAP) was diagnosed after an open lung biopsy. The diffuse infiltrates on his chest X-ray film diminished spontaneously. Two years later, diffuse infiltrates increased again with an elevated serum ACE activity. In this case, it seemed that the severity of PAP was associated with serum ACE activity. We review the literature on the relationship between serum ACE activity and dysfunction of alveolar macrophages in PAP. PMID- 7799561 TI - [Wegener's granulomatosis--report of four cases including two in patients who died of myocardial infarction]. AB - The prognosis for Wegener's granulomatosis (W-G) is good if it is diagnosed early and a combination of corticosteroids and cytotoxic drugs is given. During the past fourteen years, we were encountered four cases of W-G, three were systemic and one was limited. Of the three patients, with systemic disease, two died of myocardial infarction caused by a delay in diagnosis and one died of fulminant renal and respiratory failure. Only the one patient with a limited form of the disease survived for more than 5 years. We emphasize the importance of early diagnosis with consideration of the systemic features of W-G. PMID- 7799562 TI - [A case of small cell lung cancer associated with fulminant hepatitis B]. AB - A 48-year-old man was admitted to our hospital because of upper abdominal pain, and a cervical tumor, on Oct. 23, 1992. Chest X-ray, CT scan and MRI revealed a tumor (left-S10) and enlarged mediastinal lymph nodes. A pathological diagnosis of small cell lung cancer was made by transbronchial biopsy. Ultrasonography showed liver metastases. He received four courses of chemotherapy (Carboplatin, Ifosfamide, Etoposide). Three days after the completion of chemotherapy, his serum transaminase level was markedly increased, and he was disorientated on March 4, 1993. In spite of plasma exchange, the patient died due to hepatic failure on March 6, 1993. Fulminant hepatitis in a patient with lung cancer receiving chemotherapy is rarely reported. PMID- 7799563 TI - [Surgery of bilateral pulmonary aspergilloma]. AB - A 60-year-old man with cough and fever was admitted to our hospital. Chest radiography revealed multiple bullae and fungus balls in both lungs. He was treated with MCZ and FCZ for about 2 months, but the chest radiograph shadows did not improve and the fever continued. A two-stage operation was performed. The bullae were incised and the fungus balls were removed, then a muscle flap plombage was made with a pectoralis major muscle, a latissimus dorsi muscle and an intercostal muscle. The postoperative course was uneventful and respiratory function was preserved. PMID- 7799564 TI - [A case of chronic type farmer's lung which led to severe pulmonary fibrosis and spontaneous pneumothorax]. AB - We present a case of chronic type farmer's lung which showed progressive pulmonary fibrosis and spontaneous pneumothorax 12 years after the first admission. A 56-year-old woman was diagnosed as having farmer's lung in 1981. After the first hospitalization, her chest roentgenogram showed regression with steroid therapy. After that, she sometimes worked at a dairy farm and required rehospitalization three times for recurrence. In April 1993, she was readmitted complaining of sudden chest pain and dyspnea after cough. Her chest roentgenogram on admission showed spontaneous pneumothorax. After treatment, her chest roentgenogram revealed severe pulmonary fibrosis and loss of lung volume. PMID- 7799565 TI - [A case of interruption of the inferior vena cava with azygos continuation accompanied by anomalies of tracheobronchial branching]. AB - A 31-year-old man, asymptomatic but with an abnormal shadow adjacent to the right tracheobronchial angle on chest roentogenogram, presented to our hospital. CT and MRI of the chest revealed this shadow to be a dilated azygos arch. The inferior vena cava was interrupted, at the intrahepatic portion, by the azygos continuation. There was also an abnormality of tracheobronchial branching. The right middle lobe bronchus gave rise to the upper lobe bronchus. The right B7 was absent though the left BX7 was present. The pulmonary arteries passed over the main bronchi bilaterally. Interruption of the inferior vena cava is often associated with significant cardiovascular and abdominal anomalies but only rarely with anomalies of tracheobronchial branching. PMID- 7799567 TI - N-terminal amino acid sequence of a 28 kDa major serum high density lipoprotein of the rainbow trout Oncorhynchus mykiss. AB - As there are few data on primary structures of fish apolipoproteins (apo), we determined the N-terminal sequence of a 28 kDa major serum protein of rainbow trout, a possible homologue of apoAI protein in higher vertebrates. Rainbow trout serum was separated by two-dimensional electrophoresis. A spot of the 28 kDa protein (pl 5.45) was cut out and directly applied to a protein sequencer. We succeeded in sequencing 30 amino acids from the N-terminal. The sequence of the 28 kDa protein shared a high similarity with that of apoAI of Atlantic salmon (Salmo salar). These results showed that the 28 kDa protein is apoAI of rainbow trout. PMID- 7799566 TI - [A case of sarcoidosis associated with severe cardiac conduction disturbances and unilateral pleural effusion]. AB - A 23-year-old man was admitted to our hospital because of non-productive cough. Chest X-ray demonstrated bilateral hilar lymphadenopathy, bilateral infiltration shadows and right pleural effusion. ECG showed complete A-V block and sinus arrest. Transbronchial lung biopsy and pleural biopsy specimens showed non necrotizing epithelioid cell granulomas. The patient was diagnosed as having sarcoidosis, and was treated with steroid and pacemaker. After steroid therapy, myocardial imaging with thallium-201 showed increase of uptake and the pleural effusion disappeared. PMID- 7799568 TI - The inhibitory effects of MgSO4 on the multiplication and transcription of mouse hepatitis virus. AB - The multiplication of mouse hepatitis virus (MHV) was inhibited by the treatment of infected cells with MgSO4 at concentrations higher than 50 mM. The inhibition of viral multiplication was more effective with the treatment of cells at the early stage of infection using MgSO4 than at the late stage. Viral adsorption to the cells was not inhibited by MgSO4 and pretreatment of the cells with MgSO4 did not show an inhibitory effect on the RNA synthesis of MHV. The synthesis of viral RNA was inhibited more effectively by the treatment of infected cells with MgSO4 at 0-2 and 2-4 h postinfection (p.i.) than at 4-6 h p.i. The present study suggests that the stage at which viral multiplication is susceptible to MgSO4 may be the early stage of viral transcription and that Mg2+ may be a useful tool for the analysis of the early stage of MHV infection. PMID- 7799569 TI - [Investigation on the treatment of infection due to Mycobacterium Kansasii]. AB - Mycobacterium kansasii infection responds well to antituberculous drugs, and in the initial phase of treatment, many patients with M. kansasii infection are regarded as tuberculosis. This study was carried out to know whether the regimen of chemotherapy be continued or changed after the confirmation of diagnosis as M. kansasii infection. The treatment result of 107 cases with M. kansasii infection of the lung encountered at Fukujuji Hospital was compared with that of pulmonary tuberculosis. Sputum culture of all patients treated with drug regimens containing RFP converted to negative within 3 months after starting chemotherapy, while sputum culture of many patients treated with regimens not containing RFP converted to negative 4 months or later after the start of chemotherapy. Hence, the effectiveness of RFP in treating M. kansasii infection was confirmed. Among 65 patients with no relapse during a follow-up period of at least one year after the completion of chemotherapy, 58 patients (89.2%) were treated with drug regimens containing INH and RFP, and the treatment of 40 patients (61.5%) was finished within 12 months. Among three patients deteriorated during chemotherapy or relapsed within one year after the completion of chemotherapy, two patients were treated with drug regimens containing RFP and one of them had serious complications. The chemotherapy regimen for tuberculosis is considered to be sufficient for the initial treatment of pulmonary disease caused by M. kansasii. PMID- 7799570 TI - [Efficacy of PCR-microwell plate hybridization method (Amplicor Mycobacterium) for detection of M. tuberculosis, M. avium and/or M. intracellulare in clinical specimens]. AB - Recently, a new kit to detect and identify mycobacteria in clinical specimens was developed by Japan Roche Co. Limited. The new method is based on amplification of DNA of mycobacteria in clinical specimens by PCR and hybridization of amplified DNA by microwell plate hybridization method, which is the "Amplicor Mycobacteria, Roche, (AMP-M)". Cooperative study was organized with 15 tuberculosis hospitals and institutions throughout Japan, and 349 clinical specimens from newly admitted tuberculosis patients and/or suspects were collected during July and August, 1993. All the specimens were examined by smear microscopy (Ziehl-Neelsen's staining), culture on Ogawa egg media, culture on variant 7H9 liquid media and by AMP-M. Excluding 25 specimens which had failed to identify the species of mycobacteria because of contamination, disability to multiply on the transplanted solid media and so on, the results of the examinations in 324 specimens consisting of 167 specimens from previously untreated cases and those of 157 specimens from previously treated cases were analysed. Main results obtained were as follows; 1. Of 70 smear positive specimens from previously untreated cases, culture positive on Ogawa media and 7H9 media, and by AMP-M positive were 59 (84.3%), 61 (87.1%) and 66 (94.3%), respectively. Of 97 smear negative specimens, culture positive were 20 (20.6%), 22 (22.7%) and 27 (27.8%), respectively. The AMP-M showed the highest positive rate in both groups. 2. The sensitivity and the specificity of AMP-M in previously untreated cases were calculated by assuming that positive on Ogawa and/or variant 7H9 media is "positive". The sensitivity was 95.8% (68/71) and the specificity was 94.8% (91/96) for M. tuberculosis in previously untreated cases. The sensitivity and the specificity for M. avium and M. intracellulare were all 100%, although the numbers observed were small. 3. So called false positive of the AMP-M were observed in 5 cases out of 96 culture negatives on both Ogawa and variant 7H9 media. However, all 5 cases were positive by repeated AMP-M, 3 become culture positive later, and another 2 showed clinical findings consistent with tuberculosis. Hence, the authors considered that the false positive rate of the AMP-M method is to be very low in previously untreated cases. 4. Of 86 smear positive cases with history of previous chemotherapy, the positive culture on Ogawa media, variant 7H9 media and that by AMP-M method were 64 (74.4%), 77 (89.5%) and 85 (98.8%), respectively. In the smear negative cases, culture positive was 10 out of 71 (14.1%), 13 (18.3%) and 24 (33.8%), respectively. PMID- 7799571 TI - [A therapeutic trial of experimental tuberculosis with gamma-interferon in an immunocompromised mouse model]. AB - It has been well documented that IFN-gamma plays an important role in the host defense against Mycobacterium tuberculosis infection through activating macrophages to kill the organism. In the present study, we studied the effects of in vivo injection of monoclonal antibody against IFN-gamma (anti-IFN-gamma mAb) on the mycobacterial infection to confirm the role of this cytokine. The injection of anti-IFN-gamma mAb suppressed the enhanced expression of MHC class II and ICAM-1 on pulmonary parenchymal macrophages induced by intravenous injection of Mycobacterium bovis BCG. The number of bacilli recovered from lung of mice treated with anti-IFN-gamma mAb and injected with Mycobacterium tuberculosis H37Rv was significantly larger than that of the control infected mice. From these results, it was indicated that anti-IFN-gamma mAb blocked the activities of endogenously synthesized IFN-gamma, thus inhibited the activation of macrophages to kill the bacilli. Next, CD4+ T cell-depleted mice were prepared by injecting anti-CD4 mAb and used as immunocompromised animal. When infected with M. tuberculosis, the multiplication of the bacilli within the lungs of such immunocompromised mice was much more enhanced in comparison with the control mice with intact CD4+ T cells. Administration of IFN-gamma significantly reduced the number of the bacilli in lung. Further, in an in vitro study with human lung macrophages, IFN-gamma enhanced the killing activity of macrophages against M. tuberculosis in a dose dependent manner, and suboptimal dose of 1 alpha, 25 dihydroxyvitamin D3 synergistically augmented the effect of IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799572 TI - [A case of endobronchial tuberculosis with high serum CA19-9 and SLX level]. AB - A 43-year-old female was admitted to our hospital with mild cough, sputum and right chest pain. The chest X-ray revealed an inhomogeneous shadow in the right upper lung field and mediastinal lymphadenopathy. At first we considered the patient had bronchogenic carcinoma, as her serum CA19-9 and SLX levels were high and the right upper bronchus was obstructed by necrotic tissues. However bronchoscopic specimen showed necrotizing epithelioid cell granulomas and Mycobacterium tuberculosis was detected, and her disease was diagnosed as endobronchial tuberculosis. The case responded well to anti-tuberculosis chemotherapy. The differential diagnosis between bronchogenic carcinoma and endobronchial tuberculosis was very difficult in this case because of high serum level tumor marker and endoscopic findings, which turned to normal after treatment. We discussed the cause of high serum level of CA19-9 and SLX in nonmalignant lung disease. PMID- 7799573 TI - [A case of pulmonary tuberculosis developed immediately after a chest wall injury]. AB - A 75-year-old female was admitted to our hospital for further examination of the cause of blood-stained sputum and abnormal shadow on chest radiogram which had developed immediately after an injury of right chest wall. The bacteriological examination of sputum on admission revealed negative Gaffky score, but positive PCR, and Mycobacterium tuberculosis was isolated by culture. Her symptoms and chest radiogram were improved by the administration of isoniazid, ethambutol and rifampicin. Although development of pulmonary tuberculosis induced by chest wall injury is rare, in case of the aged persons such possibility should be considered. PCR may be useful for rapid diagnosis of tuberculosis, even in such case. PMID- 7799574 TI - [The 69th annual meeting symposium. II: Mechanism of necrotizing granuloma formation and its function]. AB - Histological features of tuberculosis are caseation necrosis and epithelioid cell granuloma formation. Both phenomena are interpreted as expression of cellular immunity. Caseation necrosis is thought to be immunopathology and epithelioid cell granuloma formation is considered to be expression of protective immunity. Recently roles of cytokines for granuloma formation are gradually elucidated. In this symposium, mechanisms and functions of necrosis and granuloma formation Dr. Akagawa reported differentiation of two types of phenotypically different macrophages from human monocytes by GM (granulocyte-macrophage)-CSF or M (macrophage)-CSF. Interestingly such a basic differentiation induced by CSF was affected by IL-4 (interleukin-4). Langerhans-like dendritic cells were generated by cooperation of GM-CSF and IL-4, and multinucleated cells were generated by cooperation of IL-4 and M-CSF. Dr. Fukuda reported human Langerhans cell granulomatosis (LCG) from the pathological and immunohistochemical standpoints. In situ proliferation of LCs in the LCG was demonstrated by immunohistochemistry using antibody to PCNA (proliferating cell nuclear antigen) which is used to detect proliferating cells. In the course of granuloma formation, damage and disruption of lung structure such as alveolar basement membrane and elastic tissue framework, and reactive intraluminar fibrosis was observed. Mechanism of cystic dilation was also reported. Cytokines might play important roles in these events. Dr. Ina demonstrated experimental epithelioid cell granuloma formation. Extract (granuloma inducing factor, GIF) from Schistosoma mansoni Egg-induced granuloma, TNF -alpha, or IL-1 beta were coated, individually on the surface of beads, then these beads were inoculated to rat's skins or cultured with rat's monocytes. Four weeks later, epithelioid cell granuloma was demonstrated histologically and electronmicroscopically around beads in vitro and in vivo. GIF induced granuloma was more organized than cytokine-induced ones. In vitro using human monocytes, activated macrophages accumulated around beads of which cytokines or GIF were coated. It was suspected that many cytokines or other factors are needed to make epithelioid cell granuloma. Dr. Sakamoto showed the presence of acid fast bacilli and various inflammatory cells including lymphocytes and macrophages in the tuberculous caseous necrosis after exudative reaction (E-necrosis) by immunohistochemistry. But no acid fast bacilli or inflammatory cells were found in the caseous necrosis after productive reaction (P-necrosis). TNF-alpha (tumor necrosis factor-alpha) and IL-4 were stained in the E-necrosis and IL-4 and ICAM-1 (intercellular adhesion molecule-1) were positively stained in the cytoplasm of epithelioid cells by immunohistochemistry. It was suspected that many cells and cytokines were involved in epithelioid cell granuloma formation and caseous necrosis formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7799575 TI - [Phagocytic activity of neutrophilic granulocytes in patients with burns during enterosorption in combined treatment]. PMID- 7799576 TI - [Use of enterosgel in middle-aged and aged patients with medium-severity burns]. AB - The comparative dynamics of intoxication and natural humoral organism resistance indexes in elderly and senile patients with burn disease of middle degree severity while application of generally used therapy and incorporating in treatment complex the enterosgel preparation prescribed since 24 hours after injury occurrence was studied. Under the enterosgel influence the intoxication syndrome intensity has been markedly decreased, what promoted the skin loss restoration, favourable burn disease course, mortality reduction, and the shortening of patients hospital stay. PMID- 7799577 TI - [Use of anti-Bacillus pyocyaneus and anti-Proteus donor plasma in combined treatment of children with severe burns]. PMID- 7799578 TI - [Treatment of burn wounds and wounds healing with secondary tightening using dressings with aerosil]. AB - The results of treatment of burn wounds and the wounds, healing with secondary closure, using the dressings containing the layer of aerosil a 2-3 mm thick, were studied. In principal group earlier than in control the decrease of wound intoxication occurred, alike the normalization of electrolyte balance, acid-base balance, and haemodynamics, improvement of patients' general condition, and the shortening of their stay in hospital was noted. PMID- 7799579 TI - [Prevention of peritonitis after surgery of the stomach and large intestine]. AB - We have used the combined preparation of foamy aerosol Gyposol-A and nitasol for the prophylaxis of postoperative peritonitis, originated due to gastrojejunal and colo-colonic anastomoses insufficiency. The introduction of preparation via the colonic tube ensures the physical hermetic control of anastomosis and allows to optimize the reparative processes by means of local antimicrobial, antiinflammatory, and stimulant action. Method was used in 76 patients. The frequency of postoperative peritonitis occurrence decreased from 20 to 2.3%. PMID- 7799580 TI - [Intralymphatic therapy of peritonitis]. AB - The lymphatic system catheterization methods, the appropriate catheterization side choice were developed by the authors. It was established that the peritonitis progress is accompanied by endolymphatic therapy effect lowering, what demands the application of active organism detoxication methods, hepatoprotective and immunocompensatory therapy. PMID- 7799581 TI - [Combined endolymphatic therapy in patients with diffuse peritonitis]. AB - The results of treatment of 25 patients with diffuse peritonitis whom the combined endolymphatic therapy was conducted in postoperative period, including the lymph irradiation with helium-neon laser and direct endolymphatic antibacterial therapy, are presented. Catheter was used introduced in peripheral lymph vessel on the dorsal surface of foot. The decrease of organism intoxication, more rapid than in control, was noted. PMID- 7799582 TI - [Diagnosis of endogenous intoxication, prognostication of the course of pathological process and principles of the establishment of a treatment program for patients with severe burns]. AB - The experience of treatment of 300 patients with burns was summarized. The ways of development of diagnostics and treatment system for endogenous intoxication syndrome in injured persons with burns are proposed. The elaborated test-system permits to define the endogenous intoxication severity and the degree of functional possibilities suppression of antitoxic resistance cytological and humoral factors. The differentiated detoxication programs are compiled. PMID- 7799583 TI - [Prognostication of the course of pancreatogenic shock in a dynamic study of central hemodynamics indices in patients with pancreatic necrosis during enzymatic toxemia stage]. AB - The investigation of central haemodynamics indexes dynamics with the use of the developed automatized system in 65 patients with pancreonecrosis was conducted for the aim of disease course prognostication and differentiated prescription of cardiotonics. Three stages of circulatory disorders were established. The possibility of patient's death significantly increases in the presence of prolonged depression of cardiac output when rapid effect of conservative therapy is absent. PMID- 7799584 TI - [Use of plasmapheresis in combined treatment of patients with severe form of generalized myasthenia]. PMID- 7799585 TI - [Surgical treatment of multistage occlusion of the abdominal aorta and iliac and femoral arteries]. AB - The results of surgical treatment of 26 patients with "multistage" occlusion, who underwent reconstructive operation on two segments (group 1), and 29 patients, who underwent ultrasound disobliteration of the femoral arteries together with the reconstructive operation (group 2), are presented. In group 1, a good immediate result was noted in 80.8%, a good long-term result--in 61.6%, in group 2--79.4 and 70.8% of the patients, respectively. PMID- 7799586 TI - [Use of different methods of quantum hemotherapy in the treatment of suppurative wounds in middle-aged and aged patients]. AB - The experience with the use of the different methods of quantum hemotherapy in the treatment of elderly and senile patients with purulent-inflammatory diseases of the soft tissues has been summarized. Comparative characteristic of their effectiveness is presented. The authors consider the most expedient the use of intravascular quantum hemotherapy and combined methods. PMID- 7799587 TI - [Surgical treatment of cerebral ischemia caused by multiple occlusions of major cerebral arteries]. AB - The case records of 205 patients with brain ischemia of various degree severity accompanied by two and more main brain arteries occlusion are analyzed. In 176 operated patients 241 revascularizing intervention was conducted. The advantages of surgical method versus conservative one were established. PMID- 7799588 TI - [Dynamics of the blood level of middle molecular mass peptides of patients with surgical endotoxicosis during plasmapheresis]. PMID- 7799589 TI - [Dynamics of changes in blood immune indicators after intralymphatic administration of gentamycin and myelopid in combined prevention of complications in ulcerative colitis and Crohn disease]. AB - To rise the effectiveness of preoperative preparation of patients with ulcerative colitis and Crohn's disease we used the endolymphatic injection of gentamycin and myelopid. This permitted to normalize the blood immune indexes in the course of 3 days. PMID- 7799590 TI - [Surgical treatment of bile duct fistula]. AB - Among 208 patients with extrahepatic biliary ducts fistula there were 60 with internal one, and 148--external one. The correction of main biliary ducts bile outflow was the principal stage of procedure. The method of correction was selected taking into account the character, level, and extent of pathological process the bile outflow impeded. The adequate surgical tactics and pathogenetically proven treatment allowed to achieve the favourable results in 96.6% of patients. PMID- 7799591 TI - [Surgical treatment of cholelithiasis]. AB - The experience with surgical treatment of cholelithiasis is presented. A method of organ-preserving operation on the gallbladder--cholecysto-extraction is presented. The operation was performed in 29 patients. The results of treatment are satisfactory. PMID- 7799592 TI - [Surgical correction of reflux gastritis]. PMID- 7799593 TI - [Surgical treatment of radiation osteomyelitis of the sternum using cutaneo muscular-mammary flap]. PMID- 7799594 TI - [Method of surgical treatment of complete intestinal fistula]. PMID- 7799595 TI - [Differential diagnosis symptom of peritoneal irritation in obese patients]. PMID- 7799596 TI - [Method of appendectomy in obturation of the vermiform process by Ascaridia]. PMID- 7799597 TI - [Use of thermovision examination in hand burns]. AB - With the use of thermovision set TVT-01 "Raduga" 17 healthy persons (control group) and 40 injured persons with the burn of various degree of severity were examined. In superficial I-II degree burn on the hand the temperature within the centre of injury exceeds normal level by 1.6-2 degrees C, and III A degree--by 2.2-2.6 degrees C. The healing of the burn wound was followed by gradual fall of her temperature, although she normalizes after epithelialization completion. In III B degree burn on the hand the temperature within the centre of injury decreases by 1.6-2.0 degrees C in comparison with the normal level. Autodermoplasty is effective only in the presence of temperature gradient between transplant zone and healthy tissues no more than 1.5 degrees C. PMID- 7799598 TI - [Method of indirect intralymphatic antibiotic therapy in acute appendicitis]. PMID- 7799599 TI - [Cutaneous-adipose plasty of the scrotum in Fournier's gangrene]. PMID- 7799600 TI - [Enterosorption in combined treatment of injured patients with burns]. PMID- 7799601 TI - [Use of film coatings in the treatment of wounds of injured with burns]. PMID- 7799602 TI - [Healing of severe burns in a patient with hemophilia]. PMID- 7799603 TI - [Combined surgical and therapeutic treatment of complicated ulcerative necrotic enterocolitis on the background of scleroderma using Salofalk preparation]. PMID- 7799604 TI - [Rare forms of hernial strangulation]. PMID- 7799605 TI - [Case report of internal paraduodenal hernia]. PMID- 7799606 TI - [Treatment of acute appendicitis at the central district hospital]. PMID- 7799607 TI - [Leiomyoma of the stomach complicated by severe hemorrhage]. PMID- 7799608 TI - [Questions of surgery in the life and works of M. A. Bulgakov]. PMID- 7799609 TI - [Evgenii Grigor'evich Cherniakhovskii (the 120th anniversary of his birth)]. PMID- 7799610 TI - [Changes in immunological reactivity during the use of enterosorption in combined treatment of children with severe burns]. AB - In 20 children with severe and extremely severe burns since the 3-4th day the enterosorption in the treatment complex was applied. The enterosorbents application have promoted the intoxication severity lowering, the decrease of the damaging action of blood formed elements on the erythrocytes of their own, the lowering of plasma toxic properties, rosette level in peripheral blood. On the 16 18th day after injury the red blood indexes have normalized, allowing to prepare the patients to the operative treatment. PMID- 7799611 TI - [Meconium aspiration in the newborn infant--lack of long-term pulmonary sequelae]. AB - The further development of newborns with meconium aspiration (MA) has been studied retrospectively by various investigators. However, results are inconsistent (2, 3, 5, 6). In the present study 25 children with MA were investigated in the age of 1 to 11 years. The parents answered a questionnaire, the children were examined physically. All the 11 children older than 5 years were subjected to spirometry, bodyplethysmography, and a histamine provocation test. An age matched control group of 28 children was investigated in the same way. No differences were found between children with MA and the control group concerning history and physical examination. Only the symptom "cough without cold" was found significantly more frequently in preschool children (1 to 5 years) with MA as compared to control children (p < 0.01). However, none of the parameters of lung function testing revealed any difference between the two groups. Also, the medians of the histamine thresholds in both samples were normal and did not differ. In summary, in a group of 25 children with MA, when compared to children without MA, only the symptom "cough without cold" was found significantly more frequently during preschool age. No evidence of long term pulmonary sequalae was seen in children with MA. PMID- 7799612 TI - [Effect of corticosteroids on lung function and the clinical course of bronchopulmonary dysplasia in premature infants with a birth weight below 1,500 g]. AB - 11 very low birth weight infants (700-1480 g) with bronchopulmonary dysplasia were treated with dexamethasone (0.5 mg/kg/day for 3 days, 0.3 mg/kg/day for 3 days), followed by hydrocortisone (tapering from 2 mg/kg/day-0.5 mg/kg/day, total 4 days). Pulmonary function tests showed a significant improvement of lung compliance from initially 0.36 +/- 0.05 cm/ml H2O/kg to 0.54 +/- 0.16 cm/ml H2O/kg after 24 hours. Compliance remained within levels above baseline during the following 4 days. Steroid therapy was also associated with a significant reduction of FiO2 (0.45 to 0.34) and ventilator rates (48.9 to 29.3/min). Extubation was possible in all infants 11.9 (+/- 10) days after initial treatment. PMID- 7799613 TI - [Ultrasound morphologic changes in periventricular leukomalacia]. AB - Therapeutic advances in neonatology cause fewer hypoxic conditions. In relation with this we observe fewer high grade brain haemorrhages. Therefore, ischemical brain changes through brain oedema (12%) and resulting colliquation necroses become the focal point of diagnostic and therapeutic work. 7.3% of intensively treated neonates showed the sonographic picture of a periventricular leucomalacy (PVL). The polycystic areas can be seen on the eight day after birth at the earliest and at six months they turn into a glia scar which is not very obvious on the sonograph. We found a relation between beta-mimetic tocolysis, hypocapnia and the development of a PVL. We were not able to prove statistically a connection with premature birth. PMID- 7799614 TI - [Cerebral infarct and hemorrhage in patients with sickle cell disease]. AB - Two sickle cell patients with cerebral accidents, infarct and bleeding, are presented. Up to 15% of all sickle cell patients suffer cerebral events, 75% of which are infarcts, 25% intracranial hemorrhages. Infarcts occur predominantly in children with a clustering around age 7, while bleeding predominates in adult life. Cerebral events are due to intimal changes, proliferation and finally occlusion of both small and large cerebral arteries. Infarcts present with hemiparesis, aphasia, loss of vision and seizures whereas intracranial bleedings are associated with severe headache and/or loss of consciousness and coma. When cerebral infarct is suspected, magnetic resonance imaging is the diagnostic method of choice. Intracranial bleeding is best diagnosed by computed tomography or angiography. Partial exchange transfusion is indicated in both events to be followed by a chronic transfusion program of as yet undetermined length. Routine magnetic resonance angiogram and/or transcranial doppler sonography in young asymptomatic sickle cell patients may make it possible in the future to detect patients at risk and institute treatment prior to a cerebral accident. PMID- 7799616 TI - [Simplified determination of proteinuria in children using a single urine sample]. AB - In children and adolescents the evaluation of proteinuria is cumbersome because of the need to obtain timed urine collections. The protein/creatinine ratio (using a Coomassie blue binding technique and a kinetic Jaffe reaction, respectively) measured in 134 pediatric patients with renal disease aged 2 months to 16 years correlated closely with the overnight urine protein excretion rates using the statistical approach suggested by Bland and Altman to compare methods of measuring some quantity. The upper limit of urinary protein/creatinine ratio measured in 252 healthy children and adolescents aged 4 to 19 years was shown to be 19 mg/mmol. No age-related differences in urinary protein excretion were noted in healthy subjects. The random urine protein/creatinine ratio provides an accurate assessment of quantitative protein excretion and avoids errors and difficulties associated with timed urine collection. PMID- 7799615 TI - [Cystic changes as an indication for infection-induced blockage of the ventriculoperitoneal shunt]. PMID- 7799617 TI - [Comparison of the luminescence enhanced enzyme immunoassay Amerlite FT4/MAB-FT4 and Amerlite FT3/MAB-FT3 in blood serum of children. Reference values]. AB - Concentrations of free thyroxine (n = 225, male = 124, female = 101) and free triiodothyronine (n = 60, male = 35, female = 25) were determined using the luminescence enhanced enzyme immunoassay methods Amerlite FT4/MAB-FT4 and Amerlite FT3/MAB-FT3 in blood-serum of children. In contrast to the excellent agreement of the results between the Amerlite FT4 and MAB-FT4 method, a significant difference was found between the Amerlite FT3 and MAB-FT3 results. Therefore it was necessary to establish new reference ranges for the MAB-FT3 method in childhood (cord blood = 50, n = 272, male = 183, female = 89). PMID- 7799618 TI - [Joubert syndrome combined with unilateral facial paralysis: a rare variant of Joubert syndrome]. AB - We report the case of a mature newborn infant, which aroused attention 8 hours after birth due to an unexplainable paroxysmal tachypnea together with subsequently prolonged apnea. The combination of tachypnea, athetoid movement patterns, apraxia of the tongue, nystagmus and dysplasia of the cerebellum with dilation of the 4th ventricle, led to the diagnosis of Joubert-Syndrome. The child also showed a variation of a connatal unilateral facial nerve palsy, which has not previously been described in connection with a Joubert-Syndrome. PMID- 7799619 TI - [Fatal course of infectious mononucleosis in an 11-month-old girl]. AB - Fatal infectious mononucleosis is vary rare in the human population. Only two case reports of girls suffering an Epstein-Barr virus-associated lymphoproliferation without evidence of an underlying immunodeficiency came to our knowledge. We report on the case of an 11-months-old girl with fatal infectious mononucleosis. Some findings allow distinct delineation from previous reports. Firstly, the present "pulmonary lymphoid hyperplasia" has been formerly described in patients with HIV infection exclusively. Secondly, only the EBV surface antigen LMP was expressed on infected B-cells. The nuclear antigen complex EBNA could not be demonstrated. Overall, the results suggest a so far unrecognised type of EBV-associated lymphoproliferation in a female infant. PMID- 7799620 TI - [Concordance of prune belly syndrome and VACTERL association]. AB - We report on a male premature infant with hypoplastic abdominal wall musculature, urinary tract anomalies and kryptorchism--the main features of Prune-Belly syndrome. Furthermore the patient showed cardiac anomalies, urinary tract anomalies, limb defects, vertebral anomalies and anal atresia, which belong to the main features of VACTERL-association. As far as we know, the combination of the Prune-Belly-syndrome and the VACTERL-association has not been reported in literature until now. PMID- 7799622 TI - Adhesion strength of human ligament fibroblasts. AB - The adhesive interactions of cells with other cells and the extracellular matrix (ECM) play a fundamental role in the organization of cells in differentiated organs, cell motility, and the healing process. The adhesion characteristics of ligament fibroblasts depend on the expression of cell surface molecules and their interaction with the ECM. Although many receptors mediating the effects of ECM components on ligament cell function remain poorly defined, it is known that fibronectin (FN) allows ligament cells to adhere through the VLA-5 receptor (alpha 5 beta 1). A direct measurement of the adhesion between anterior cruciate ligament (ACL) or medial collateral ligament (MCL) fibroblasts and fibronectin matrix proteins was achieved by using a micromanipulation technique to determine the force required to detach an ACL or MCL cell from fibronectin-coated glass. We have found that the adhesion strength is not random, but has well-defined functional relationships with the FN concentration and the seeding time (time allowed for the cell to establish attachment). The adhesion strength (i.e., force required to detach) of ACL cells shows a stronger dependence on FN concentration (1, 2, and 5 micrograms/ml) for short seeding times (15-30 min) than for long seeding times (38-75 min). For MCL cells, the effect of the seeding time on adhesion strength was apparent for all concentrations. For all the seeding times studied and FN concentrations used, MCL cells had higher adhesion strength than ACL cells. The adhesion strengths of ACL and MCL fibroblasts to FN are correlated to cell adhesion area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799623 TI - A model for motion and sedimentation of cylindrical red-cell aggregates during slow blood flow in narrow horizontal tubes. AB - When blood flows slowly in a narrow tube, red-cell aggregation results in formation of an approximately cylindrical "core" of red cells, which moves as a rigid body. The core is denser than the surrounding fluid, and sedimentation is observed in horizontal tubes. To model this, the Stokes flow of a fluid surrounding a long solid cylinder (the core) contained in a long hollow cylinder (the tube) is considered. The cylinder axes are parallel but not coincident. An exact analytic expression for the resistance coefficient for motion perpendicular to the axes is given. This coefficient increases rapidly with the ratio of core radius to tube radius, and core eccentricity. The predicted rate of sedimentation is comparable to that observed experimentally. The apparent viscosity of a two phase medium consisting of a core of aggregated particles and surrounding pure fluid is calculated. For a core radius corresponding to experimental conditions, the apparent viscosity increases rapidly with increasing eccentricity of the core. PMID- 7799624 TI - A finite element model of skin subjected to a flash fire. AB - A variable property, multiple layer finite element model was developed to predict skin temperatures and times to second and third degree burns under simulated flash fire conditions. A sensitivity study of burn predictions to variations in thermal physical properties of skin was undertaken using this model. It was found that variations in these properties over the ranges used in multiple layer skin models had minimal effects on second degree burn predictions, but large effects on third degree burn predictions. It was also found that the blood perfusion source term in Pennes' bioheat transfer equation could be neglected in predicting second and third degree burns due to flash fires. The predictions from this model were also compared with those from the closed form solution of this equation, which has been used in the literature for making burn predictions from accidents similar to flash fires. PMID- 7799621 TI - [Association of Saethre-Chotzen and fra-X syndrome]. AB - Report of an association of Saethre-Chotzen- and fragile X-Syndrome in a 19-years old imbecile with autism and aggressiveness. Both syndromes exhibit symptoms of minimal brain damage and disorders of personality. PMID- 7799625 TI - The simulation of discrete vessel effects in experimental hyperthermia. AB - The ability of two simple thermal models to predict experimentally measured in vivo temperature profiles was compared. These comparisons were done both with and without the inclusion of separate, discrete blood vessels. The two tissue models were: 1) Pennes' Bio-Heat Transfer equation (BHTE), and 2) an effective thermal conductivity equation (ETCE). The experimental temperature data were measured (Moros, 1990; Moros et al., 1993) in the thighs of anesthetized greyhound dogs under hyperthermic conditions generated by scanned focused ultrasound. Blood vessels were added to the thermal models in counter-current pairs transiting the model domain. The blood vessels in both models were assumed to have a constant heat transfer coefficient, and an axially varying mixed mean temperature. The vessel locations were determined a posteriori, via inspection of the experimental temperature data. Least square error fits of the predicted model temperatures to the experimental temperature data were obtained by adjusting both (a) the mass flow rate within and (b) the position of each blood vessel, and (c) the value of either the perfusion parameter (W) in the BHTE or the effective thermal conductivity parameter (Keff) in the ETCE. When small numbers (3-4) of blood vessel pairs were included, both of the models showed significant improvement in their ability to predict the experimental temperatures. Although both models performed well in terms of predicting temperatures near large vessels, the BHTE had a statistically significant better ability to predict the complete set of measured temperatures at all locations. PMID- 7799626 TI - A theoretical model of infant incubator dynamics. AB - A spatially lumped mathematical model was developed and used for a computer simulation of the neonate-incubator system for parametric analysis of the factors that influence neonatal thermo-regulation. The simulation examined the effects of the following parameters: (1) size of the infant; (2) respiratory rate; (3) metabolic rate; (4) heart rate; (5) thermal properties of the mattress; (6) specific heat capacity of the incubator wall; (7) air flow rate; (8) heater control mechanisms. PMID- 7799627 TI - Comparison of arm up and down in side impacts with BioSID and different armrests. AB - BioSID dummy tests were run with the arm down at the side during loading of different armrests in simulated side impact crashes. The Hyge sled tests duplicated previous studies of BioSID with the arm up, SID, and animals. When the BioSID arm is against the side, the arm extends from the shoulder to the bottom of the third rib and has a steel shank covered by foam and vinyl. Loading through the arm transfers force to the three chest ribs and shoulder. In comparison, direct armrest loading of the chest or abdomen primarily involves a single rib and substantial rib deflection, when the armrest crush-force exceeds the strength of the rib. The Viscous response in BioSID showed the greatest difference of all criteria for the arm up or down. The response of the third rib correlated with injury risks determined from animal tests using the different armrest designs in a simulated high position. While injury data are not available for the arm at the side or for the armrest in the low position, the STIFF armrest may cause injury when the arm is not at the side and the armrest loads the liver and spleen. Rib deflection in BioSID showed the protrusion of the STIFF armrest into the abdominal region in both arm positions, because the loading was below the arm even in the down position. However, the arm extends laterally so it involves the upper ribs earlier than in the arm-up condition where more space is available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799628 TI - Mechanical and dimensional adaptation of rat aorta to hypertension. AB - To investigate mechanisms of the mechanical adaptation of soft biological tissues to load, effects of hypertension on the mechanical properties and wall dimensions of thoracic aortas were studied in rats. Goldblatt hypertension was induced in male Wistar rats aged 8 to 9 weeks by constricting their left renal arteries. Two, 4, 8, or 16 weeks after the operation, thoracic aortas were excised and used to determine static pressure-diameter relations and wall dimensions. Wall thickness correlated significantly with the systolic blood pressure before sacrifice, Psys, at each period. The aortic hoop stress became almost constant at all Psys 2 weeks after the operation. On the other hand, the stress calculated for 100 and 200 mmHg correlated negatively with Psys. The incremental elastic modulus of the wall at Psys had a significant correlation with Psys having a positive slope at each period, although the correlation disappeared at 16 weeks after the operation. These results imply that: 1) thickness of the aortic wall increases very rapidly in response to hypertension; 2) wall stress developed by the in-situ blood pressure is kept constant at a normal level irrespective of hypertension; 3) elastic modulus of the wall of the hypertensive rats at the in situ blood pressure becomes equal to the normal value after relatively long period of time; 4) in response to the alteration of the applied force, dimensional change appears much earlier than the change in the elastic properties. PMID- 7799629 TI - Aortic walls in atherosclerotic rabbits--mechanical study. AB - Mechanical properties of the descending thoracic aortae harvested from endothelial cell-denuded and/or cholesterol diet-fed rabbits were studied primarily with their pressure-diameter relationships. Male Japanese white rabbits having 3.1 to 3.5 kg initial body weight were divided into 4 groups. The rabbits in Groups A and C were fed a regular chow, while those in Groups B and D were given 1 percent cholesterol diet; the luminal surfaces of the descending thoracic aortae in the rabbits of Groups C and D were injured by drawing catheter-tip balloons. These animals were sacrificed after keeping for 4, 8, 16 or 32 weeks and, then, their descending thoracic aortae were excised for the studies of pressure-diameter relationships. Stiffness parameter (beta") and incremental elastic modulus (H theta theta were used to quantitatively represent the structural stiffness of the aortic wall and the elastic modulus of the wall material, respectively. Denudation of endothelial cells thickened the aortic walls in Group C, but induced no significant changes in beta" and H theta theta. Shape of the pressure-diameter curve changed gradually with time in Group D, and beta", H theta theta, and thickness to wall radius ratio increased significantly, while those in Group B showed no significant changes with a few exceptions. Averaged percent fraction of the luminal surface area stained with Sudan IV (As) was around 50 percent in Group B and 100 percent in Group D at 32 weeks. Even if As is over 80 percent in Group D, 50 percent (7/14) of the walls gave significantly higher beta"- and H theta theta-values at 100 mm Hg than the others. Significantly increased calcification and intimal hyperplasia were observed in the walls with high beta"- and H theta theta-values. PMID- 7799631 TI - Preliminary analysis of the effects of blood vessel movement on blood flow patterns in the coronary arteries. AB - Blood flow patterns are believed to be involved in the formation and progression of arterial diseases. It is possible that the normal physiologic movement of blood vessels during the cardiac cycle affects blood flow patterns significantly. For example, the contraction of the heart in systole and subsequent relaxation in diastole create movements of the coronary arteries, as evidenced in real-time angiography. The effects of this movement on coronary artery flow patterns have never been previously analyzed. This work was undertaken to provide a preliminary estimate of the importance of the effects of such physiologic movements on blood flow patterns in the coronary arteries. A Womersley-type solution was used to determine the effect of axial movement on the wall shear rate in a simplified model of the coronary arteries. The pulsatile pressure gradient was derived from previously published coronary artery flow waveforms. The axial movement function was obtained from a three-dimensional reconstruction of a biplanar coronary angiogram. Significant changes in wall shear rate were noted when the movement was taken into account. The maximum and minimum wall shear rates were 10 percent smaller and 107 percent larger in magnitude respectively, and the Oscillatory Shear Index (OSI) was doubled. Most of the changes in wall shear rate were observed in systole, when the pressure gradient is minimal and the movement is strongest. The results indicate that blood vessel movement during the cardiac cycle has a significant effect on hemodynamic phenomena which have been associated with the development of atherosclerosis. PMID- 7799630 TI - The effect of wall distensibility on flow in a two-dimensional end-to-side anastomosis. AB - The development of intimal hyperplasia at the distal anastomosis is the major cause of long-term bypass graft failure. To evaluate the suspected role of hemodynamic factors in the pathogenesis of distal intimal hyperplasia, an understanding of anastomotic flow patterns is essential. Due to the complexity of arterial flow, model studies typically make simplifying assumptions, such as treating the artery and graft walls as rigid. In the present study this restriction is relaxed to consider the effects of vessel wall distensibility on anastomotic flow patterns. Flow was simulated in an idealized 2-D distensible end to-side anastomosis model, using parameters appropriate for the distal circulation and assuming a purely elastic artery wall. A novel numerical approach was developed in which the wall velocities are solved simultaneously with the fluid and pressure fields, while the wall displacements are treated via an iterative update. Both the rigid and distensible cases indicated the presence of elevated temporal variations and low average magnitudes of wall shear stress at sites known to be susceptible to the development of intimal hyperplasia. At these same sites, large spatial gradients of wall shear stress were also noted. Comparison between distensible-walled and corresponding rigid-walled simulations showed moderate changes in wall shear stress at isolated locations, primarily the bed, toe and heel. For example, in the case of a distensible geometry and a physiologic pressure waveform, the heel experienced a 38 percent increase in cycle-averaged shear stress, with a corresponding 15 percent reduction in shear stress variability, both relative to the corresponding values in the rigid-walled case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799633 TI - A computational method for solving arbitrary two-dimensional physiological flows. PMID- 7799632 TI - A computational study of a thin-walled three-dimensional left ventricle during early systole. AB - A numerical study was conducted to solve the three-dimensional Navier-Stokes equations for time-dependent flow in a compliant thin-walled, anatomically correct left ventricle during early systole. Model parameters were selected so that the simulation results could be compared to clinical data. The results produced endocardial wall motion which was consistent with human heart data, and velocity fields consistent with those occurring in a normally-contracting left ventricle. During isovolumetric contraction the posterior wall moved basally and posteriorly, while the septal wall moved apically and anteriorly. During ejection, the short axis of the ventricle decreased 1.1 mm and the long axis increased 4.2 mm. At the end of the isovolumetric contraction, most of the flow field was moving form the apex toward the base with recirculation regions at the small pocket formed by the concave anterior leaflet, adjacent to the septal wall and near the left ventricular posterior wall. Fluid velocities in the outflow tract matched NMR data to within 10 percent. The results were also consistent with clinical measurements of mitral valve-papillary muscle apparatus displacement, and changes in the mitral valve annular area. The results of the present study show that the thin-walled, three-dimensional left ventricular model simulates observed normal heart phenomena. Validation of this model permits further studies to be performed which involve altered ventricular function due to a variety of cardiac diseases. PMID- 7799634 TI - Steady expiratory flow in a model symmetric bifurcation. AB - A model symmetric bifurcation was employed to simulate steady expiratory flow in the upper part of the human central airways. A two color, two component laser Doppler anemometer was used to measure both the axial flow and the secondary flow at three different Reynolds numbers of 518, 1036, and 2089, corresponding to Dean numbers of 98, 196, and 395. The test section is a symmetric bifurcation of constant cross-sectional area with a branching angle of 70 degrees. The flow rate into the two daughter branches was about the same. Results show that in the junction plane, velocity profiles in the daughter branches are skewed towards the inner walls. In the parent tube, just downstream of the flow divider, the velocity profile is biconcave with a dip at the center but this is rapidly transformed into a velocity peak. In a plane transverse to the bifurcation plane, parabolic velocity distribution was conserved through the daughter branches. In the parent tube, the transverse profiles became flat downstream of the flow divider and developed a defect at the center further downstream towards the end of the parent tube part of the bifurcation. The velocity defect was confined to a small region in the vicinity of the centerline. Helical motion typified by symmetric vortices was observed in the daughter branches. In the parent tube, a set of four vortices induced by the turning of the flow was observed. PMID- 7799635 TI - Estimation of the thermal effect of blood flow in a branching countercurrent network using a three-dimensional vascular model. AB - A three-dimensional thermal model is presented in which convective heat transfer is defined in terms of the physical details of the vascular system. The convective heat exchange between prearteriole and postvenule vessels and the tissue across the vessel walls is calculated explicitly without using shape factors. Conduction in x-, y-, and z-direction is considered. This vascular model is applied to a human extremity. The spatial variations in the arterial, venous and tissue temperatures under basal conditions, hyperthermic conditions and in a cold environment are computed. Conclusions are drawn as to the validity of bioheat approaches. PMID- 7799636 TI - The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: a numerical model study. AB - Flow in distal end-to-side anastomoses of iliofemoral artery bypass grafts was simulated using a steady flow, three-dimensional numerical model. With the proximal artery occluded, anastomotic angles were varied over 20, 30, 40, 45, 50, 60 and 70 deg while the inlet Reynolds numbers were 100 and 205. Fully developed flow in the graft became somewhat skewed toward the inner wall with increasing angle for both Reynolds numbers. Separated flow regions were seen along the inner arterial wall (toe region) for angles > or = 60 deg at Re = 100 and for angles > or = 45 deg at Re = 205 while a stagnation point existed along the outer arterial wall (floor region) for all cases which moved downstream relative to the toe of the anastomosis with decreasing angles. Normalized shear rates (NSR) along the arterial wall varied widely throughout the anastomotic region with negative values seen in the separation zones and upstream of the stagnation points which increased in magnitude with angle. The NSR increased with distance downstream of the stagnation point and with magnitudes which increased with the angle. Compared with observations from chronic in vivo studies, these results appear to support the hypothesis of greater intimal hyperplasia occurring in regions of low fluid shear. PMID- 7799637 TI - Pulsatile velocity measurements in a model of the human abdominal aorta under resting conditions. AB - Oscillations in near-wall velocity direction have been found to correlate with atherosclerotic plaque localization in the carotid sinus bifurcation. However, it remains unproven whether these conditions could account for the localization of the disease at other sites where atherosclerosis forms. The abdominal aorta is an important site of clinical disease in a relatively straight segment of artery. This study was initiated to quantify the velocity field in the abdominal aorta in order to determine if local differences in hemodynamic velocity directions could account for the localization of disease in this segment. Magnetic Resonance Imaging velocimetry was used to measure the pulsatile velocity profiles in an anatomically accurate in vitro model of the abdominal aorta. Velocities measured in the suprarenal aorta were laminar and reversed minimally, comparing well with theoretical solutions of Womersley flow (r = 0.96). The time-averaged velocity was +3.0 cm/s near-wall at a distance of 1 mm away from the wall. In the infrarenal aorta, the maximal velocities were skewed toward the anterior wall. At the posterior wall, velocity oscillated in direction and was retrograde for 82 percent of the cardiac cycle. The time-averaged velocity near the posterior wall was -12.5 cm/s as compared to +3.00 cm/s near the anterior wall. At the aortic bifurcation, the locations of maximal and minimal velocities in this slice were concentrated near the lateral posterior walls. This study quantifies the magnitude of low and oscillatory velocity that may exist in the abdominal aorta and suggests that there is a strong relationship between the velocities in the retrograde direction under resting conditions and the distribution of atherosclerotic plaque. PMID- 7799638 TI - Influence of abdominal aortic curvature and resting versus exercise conditions on velocity fields in the normal abdominal aortic bifurcation. AB - Local hemodynamics are considered an important atherogenetic factor in the abdominal aortic bifurcation. This study addresses the quantitative flow fields in a pulsatile flow model of a normal abdominal aortic bifurcation when encountering realistic upstream anatomy, realistic inlet flow conditions and different physiologic flow conditions (rest vs. exercise). Two-dimensional laser Doppler anemometry measurements gave axial as well as radial velocities. The localization and magnitude of peak velocities, retrograde flow and secondary velocity patterns were found to be determined to a great extent by the curvature of the abdominal aorta, the triphasic flow wave form and the inlet velocity profile. Significant changes were also seen when simulating different physiologic flow conditions. Thus retrograde velocities were present at both the flow divider and the lateral vessel wall for the rest condition but not for the exercise flow conditions, and the location of low and retrograde velocities during diastole were as much determined by abdominal aortic curvature as by the bifurcation for nearly all flow conditions and locations. In conclusion, the anatomy and hemodynamics in the abdominal aorta cannot be neglected when studying the hemodynamics in the abdominal aortic bifurcation. PMID- 7799639 TI - Unsteady entrance flow development in a straight tube. AB - The entrance conditions for pulsatile flow are important in the understanding blood flow out of the heart and in developing regions at branches. The pulsatile entrance flow was solved using a spectral element simulation of the full unsteady Navier-Stokes equations. A mean Reynolds number of 200 and a range of Womersley parameters from 1.8 to 12.5 was used for a sinusoidal inlet flow waveform 1 + sin (omega t). Variations in the entrance length were observed during the pulsatile cycle. The amplitude of the entrance length variation decreased with an increase in the Womersley parameter. The phase lag between the entrance length and the inlet flow waveform increased for Womersley parameter alpha up to 5.0 and decreased for alpha larger than 5.0. For low alpha, the maximum entrance length during pulsatile flow was approximately the same as the steady entrance length for the peak flow. For high varies; is directly proportional to, the pulsatile entrance length was more uniform during the cycle and tended to the entrance length for the mean flow. The wall shear rate reached its far downstream value after only about half of the entrance length and also exhibited a dependence on alpha. The results quantify the entrance conditions typically encountered in studies of the arterial system. PMID- 7799640 TI - Derivation of shear rates from near-wall LDA measurements under steady and pulsatile flow conditions. AB - Atherosclerosis, thrombosis, and intimal hyperplasia are major forms of cardiovascular diseases in the United States. Previous studies indicate a significant correlation between hemodynamics, in particular, wall shear rate, and pathology of the arterial walls. While results of these studies implicate morphologic and functional changes related to wall shear rate magnitude, a standard technique for wall shear rate measurement has not been established. In this study, theoretical and in-vitro experimental fully developed steady and physiologic pulsatile flow waveforms have been used to obtain velocity profiles in the near-wall region. The estimated wall shear rates from these results are compared to the theoretical value to assess the accuracy of the approximating technique. Experimentally obtained results from LDA suggest that in order to minimize the error in velocity data, and subsequently, the wall shear rate, the first measured velocity has to be 500 microns away from the wall. While a linear approximation did not produce errors larger than 16.4 percent at peak systole, these errors substantially increased as the velocity magnitudes decreased during late systole and diastole. Overall, a third degree polynomial curve fit using four points produced the most accurate estimation of wall shear rate through out the cardiac cycle. Results of higher degree curve-fitting functions can be unpredictable due to potential oscillations of the function near the wall. Hence, based on the results of this study, use of a linear approximation is not recommended; a third degree curve-fitting polynomial, using four points provided the most accurate approximation for these flow waveforms. PMID- 7799641 TI - Pulsatile flow and endothelial cell morphology in a cell culture chamber model of an artificial cardiac ventricle. PMID- 7799642 TI - A multi-degree of freedom system for biomechanical testing. AB - A system is described that allows axial, torsional, and bending testing of biomechanical specimens. The system uses electric motors under closed loop control in its grips allowing application of pure bending moments. These grips attach to an axial/torsional testing system. Thus, it provides simultaneous closed loop control of all three degrees of freedom (D.O.F), so that under any given test condition either the loads or the displacements for each D.O.F. can be maintained at zero, selected constant values, or simultaneously controlled. This enables the expedient evaluation of the mechanical behavior of biological structures under complex loadings or simple loadings (one D.O.F.) with no artificially induced constraints in the other two D.O.F.'s due to specimen mounting. PMID- 7799643 TI - A note on the reduced creep function corresponding to the quasi-linear visco elastic model proposed by Fung. AB - For description of the visco-elastic behavior of soft biological tissues, Fung proposed a visco-elastic model formulated in terms of a relaxation function and corresponding relaxation spectrum. For the corresponding creep function, Fung proposed an expression which needs correction to obtain a consistent formulation. This creep function and the corresponding creep spectrum are derived in this note. PMID- 7799644 TI - Myocardial salvage by 1-O-hexadecyl-Sn-glycerol: possible role of peroxisomal dysfunction in ischemia reperfusion injury. AB - A recent study demonstrated biochemical and structural alterations of peroxisomes in rat kidney after ischemia/reperfusion. We examined whether peroxisomes play any role in the pathophysiology of myocardial ischemia/reperfusion injury. Isolated perfused rat heart was made ischemic for 30 min by terminating coronary flow (CF), followed by 30-min reperfusion. Experiments were divided into two groups; the experimental group received 1-O-hexadecyl-Sn-glycerol (chimyl alcohol) (25, 50, and 100 microM) before ischemia, and the control group received an equivalent amount of saline. Two of the experimental groups (50 and 100 microM) demonstrated improved postischemic myocardial performance, as demonstrated by accelerated recovery in left ventricular developed pressure (LVDP) and CF, as well as reduction in the incidence of ventricular fibrillation (VF). However, because the heart rate (HR) was significantly reduced in the 100 microM chimyl alcohol group, subsequent studies were performed with 50 microM chimyl alcohol as the optimal dose. Chimyl alcohol (50 microM) also reduced cellular injury, as evidenced by reduced creatine kinase (CK) release, and decreased development of oxidative stress, as evidenced by reduced formation of malonaldehyde (MDA). Peroxisomal catalase activity was decreased in the control group after ischemia/reperfusion, and chimyl alcohol treatment restored the activity of the enzyme. Our results indicate that chimyl alcohol, a precursor of ether-linked phosphoglyceride biosynthesis, can reduce myocardial ischemia/reperfusion injury, possibly by restoring catalase activity and reducing oxidative stress through synthesis of ether lipids, suggesting a possible role of peroxisomal disorder in ischemia/reperfusion injury. PMID- 7799645 TI - Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol fed rabbits. AB - We investigated the effect of perindopril, a novel angiotensin-converting enzyme (ACE) inhibitor, on neointima formation in vessel walls after balloon injury in rats (carotid artery) and cholesterol-fed rabbits (thoracic aorta). Continuous treatment with perindopril significantly reduced neointima formation in both species, as compared with the control group: intima/media (I/M) ratio (rats -62%; p < 0.001; rabbits -25%, p < 0.05); neointima area (rats -65%, p < 0.01; rabbits 24%, p < 0.05). These changes involved reduction of intimal smooth muscle cells (SMC) in rats and of macrophages in rabbits. Furthermore, perindopril also significantly decreased ACE activity in both aortic tissue and serum [11.38 +/- 0.87 vs. 34.93 +/- 6.44 pmol His-Leu (HL)/mg/min (p < 0.01) and 2.79 +/- 0.28 vs. 38.50 +/- 5.41 pmol HL/mg/min (p < 0.001), respectively], aortic contraction evoked by angiotensin I (AI) and mean blood pressure (BP, 84.9 +/- 3.5 vs. 109.3 +/- 3.8 mm Hg, p < 0.001) as compared with control values. These results indicate that perindopril may reduce neointima formation by suppressing the aortic renin angiotensin system (RAS). These findings indicate that perindopril may be capable of preventing restenotic lesions after angioplasty in humans [corrected]. PMID- 7799646 TI - Clinical and experimental studies in treating diabetes mellitus by acupuncture. PMID- 7799647 TI - Treatment of 51 cases of hyperthyroidism by puncturing effective points. PMID- 7799648 TI - 124 cases of dyssomnia treated with acupuncture at sishencong points. PMID- 7799649 TI - Acupuncture at jianjing for treatment of achalasia of the cardia. PMID- 7799650 TI - Prompt pressure applied to peculiar points in the treatment of spasmodic infantile cerebral palsy--a report of 318 cases. AB - Infantile cerebral palsy is a nonprogressive central motor disturbance of varied etiology. The spasmodic type is its main form, accounting for 50-60% of the infants afflicted with the disease. The causal factors include multifarious conditions arising during parturition and in the pre- and postnatal periods. As yet there is no specific treatment for the disease. We have used a method of applying prompt pressure to peculiar points in treating it and received satisfactory results. The present group comprised 318 patients treated for the disease by the method of prompt pressure applied to peculiar points combined with appropriate orthopedic manipulations, resulting in a 73.27% rate of good to excellent therapeutic effect. Follow-up exam was done in 52 cases, among which the efficacy was assessed as stable in 21 cases, and the remaining 31 cases as being in an improved condition. Infantile peculiar points are points peculiar to infants, mostly located in the head and extremities, and constitute an important component part of the treasure-house of traditional Chinese medicine. The method recommended here is simple and convenient, causing little pain in the invalid yet showing a marked therapeutic effect, and therefore can be regarded as a new way for treating infantile cerebral palsy. PMID- 7799652 TI - Treatment of intraperitoneal inflammatory masses with the heat and stagnation dispelling decoction--a report of 32 cases. PMID- 7799651 TI - 52 cases of apoplexy treated with scalp acupuncture by the slow-rapid reinforcing reducing method. AB - 85 cases of apoplexy were treated with scalp acupuncture, including 52 cases by the method of slow-rapid reinforcing-reducing and 33 cases by the method of flat twisting. The total effective rates differed insignificantly between the 2 methods. However, in respects of improving the myodynamia and motile functional disturbances of the limbs, the method of slow-rapid reinforcing-reducing was markedly superior to the method of flat twisting. PMID- 7799653 TI - Treating subluxation of sacroiliac joint by manipulation--a report of 100 cases. PMID- 7799654 TI - The effect of radix Salviae Miltiorrhizae Composita on peroxidation of low density lipoprotein due to copper dichloride. AB - It is well known that plasma lipoprotein, particularly oxidized LDL, plays an important role in the pathogenesis of atherosclerosis and atherosclerotic diseases. We used oxidized LDL generated by incubating LDL from healthy persons with copper dichloride as a model to investigate the antioxidate property of Radix Salviae Miltiorrhizae Composita (RSMC). On photos, the spot X1 and the spot X2 were clearly found in the control group after the dialysis into copper dichloride for 24 and 48 hours, but they could not found in the RSMC group. The analysis of the constituents of lipids in LDL (by charring method) showed that after dialysis the percentages of the spot X1 and the spot X2 in the RSMC group were significantly lower than those in the control group (P < 0.01). The results suggest that RSMC plays a potential role in antioxidation of lipids or LDL. PMID- 7799655 TI - Experimental study on effect of traditional bone-knitting drugs on traumatic gu bi (bone-rheumatoid lesions). AB - Traditional bone-knitting drugs (TBKD) are used frequently in the treatment of bone fractures. An animal model of Gu Bi (bone-related rheumatoid lesions) with defects of articular cartilage as the main lesion was developed by surgical trauma under the stereomicroscope in Wistar rats and treated with TBKD. The results showed that TBKD could promote proliferation of cartilage cells around the traumatic site and improve the osteogenetic function in the traumatic state, suggesting that TBKD can be used in combination with other Chinese drugs to treat Gu Bi, including bony lesions of the late-stage rheumatoid arthritis and bony arthritis. But the experimental results also suggested that TBKD might have an effect of promoting development of inflammation, and therefore, should be used with care in the acute phase of inflammation. PMID- 7799656 TI - Study on preventive and curative effects of liu wei di huang tang on tumors. AB - Liu Wei Di Huang Tang (LWDHT), a Chinese prescription for strengthening the body resistance, restoring the normal functions of the body to consolidate the constitution, and nourishing and invigorating the kidney yin, has been used to prevent and treat severe hyperplasia of esophageal epithelium for many years. The results of this experiment show that LWDHT can increase markedly the number of lymphocytes, mainly T lymphocytes, in tumor-bearing mice. Free-flow electrophoresis shows that in tumor-bearing mice the electrophoretic characteristics of T lymphocytes are changed, i.e., reduction of the number of T lymphocytes with a higher electrophoretic rate, but LWDHT can alleviate this disorder. Study on the cell membrane fluidity of carcinoma cells in EAC mice demonstrates that LWDHT can decrease the cell membrane fluidity, suggesting that it can inhibit division of carcinoma cells. PMID- 7799657 TI - The difference in EEG theta waves between concentrative and non-concentrative qigong states--a power spectrum and topographic mapping study. AB - The differences in EEG theta waves between concentrative and non-concentrative Qigong states were studied by means of power spectrum analysis and EEG mapping. The adult subjects included 20 practitioners of concentrative Qigong, 30 practitioners of non-concentrative Qigong and 23 control subjects. The results showed frontal mid-line theta rhythm was related to concentrative Qigong state. As the theta rhythm has been suggested to be one of the normal EEG patterns occurring in mental concentration, it is concluded that the theta rhythm is an indicator of mental concentration during Qigong state. This finding clarifies the implication of the theta rhythms appearing in Qigong and other meditation. PMID- 7799658 TI - Achievements in the treatment of hyperlipidemia with TCM-WM. PMID- 7799659 TI - Studies on reducing and reinforcing manipulation of acupuncture during the past 4 years. PMID- 7799660 TI - Treatment of chronic gastritis with acupuncture. PMID- 7799661 TI - Headache. PMID- 7799662 TI - [Changes in the cerebral flow velocity induced in the middle cerebral artery by acute stress studied by transcranial Doppler ultrasonography]. AB - BACKGROUND: The behavior of brain flow on acute stress has not been previously evaluated. Transcranial Doppler ultrasonography (TD) is a bloodless method to evaluate the speed of cerebral flow in the arteries of the Willis polygon. The present study was designed to analyze the changes which occur in the same during two situations of acute stress. METHODS: The mean speed of cerebral flow (MS) and the pulsation rate (PR) of the right and left middle cerebral artery (MCA) were measured basally and following a mental stress test (calculation) and physical stress (cold test) by TD and through the temporal window. Twenty-five healthy volunteers (18 women and 8 men) with a mean age of 27.8 +/- 7.3 years were studied. RESULTS: In response to mental stress an increase was observed in MS in both the right MCA (10 +/- 8.6 cm/sec) and the left MCA (10.4 +/- 8.7 cm/sec) with a decrease in the MCA (0.14 +/- 0.23 in the right MCA, 0.14 +/- 0.18 cm/sec in the left MCA). In response to the cold test an increase in MS (7.3 +/- 7.5 cm/sec in the right MCA, 14.8 +/- 14.7 cm/sec in the left MCA) was also observed with a decrease in the PR (0.2 +/- 0.2 in the right MCA and 0.2 +/- 0.16 in the left MCA). No significant differences were observed in the changes induced in the right or left artery or in those induced by the mental or cold tests. CONCLUSIONS: These results suggest that the acute stress produces an increase in cerebral flow in the arteries of the Willis polygon. PMID- 7799663 TI - [Dietary habits of 2 populations of the province of Barcelona (III): energy consumption and macronutrients]. AB - BACKGROUND: The identification of an association between alimentary and nutritional factors and different diseases has led to the study of alimentary habits in different populations. The consumption of energy and macronutrients was analyzed in two urban populations in the province of Barcelona (Spain). METHODS: One thousand thirty-four randomly selected individuals from primary care centers (PCC) were studied by a systematic sampling of all the out patient consultations over one year and to those to whom a semiquantitative questionnaire of frequency foodstuffs was given to estimate their normal diet. The subjects included all those residents in the two towns studied from 13 to 80 years of age who attended the PCC during the study period. RESULTS: The percentage of subjects from Vilanova i la Geltru who were found to be high consumers of milk and derivatives, fish and vegetables was significantly higher in comparison with subjects from Gava. The males of both towns presented a higher mean consumption of carbohydrates and energy than the females. On comparison of the consumption between the 2 populations, the mean carbohydrate diet ingested was significantly greater in the population from Gava in both sexes as was the consumption of energy and total lipids between women and men, respectively. CONCLUSIONS: The population studied presented a clear pattern of Mediterranean diet consumption with elevated ingestion of carbohydrates and monounsaturated fats. PMID- 7799664 TI - [Mortality in the acute phase of cerebrovascular disease: the registry of La Alianza-Hospital Central of Barcelona]. AB - BACKGROUND: Few studies have been performed on mortality from acute cerebrovascular disease (ACVD) during hospital admission, particularly in Spain. METHODS: A prospective clinical analysis was performed in 1,356 consecutive patients with ACVD included in the Registry of Cerebrovascular Disease of the Central La Alianza-Hospital in Barcelona (1986-1992) with the aim of analyzing the causes of mortality during the acute phase of the disease and the time of hospital survival. RESULTS: The mortality of the series was 16% (13% from cerebral infarction and 29% from cerebral hemorrhage; p < 0.0001). The causes of mortality were not neurologic in 49%, neurologic in 42% and of unknown cause in 9%. The principal causes of death were: transtentorial herniation/compression of the cerebral trunk (TH/CCT) 34%, pneumonia 14%, sepsis 14% and heart disease 11%. TH/CCT was more frequent on hemorrhage than on cerebral infarction (50% vs 27%; p < 0.001) while heart diseases were more frequent in cerebral infarction (14% vs 3%, p < 0.03). TH/CCT was the most common cause of death during the first seven days, with the pneumonia-sepsis-pulmonary thromboembolism being the most common after the third week. On the other hand, heart disease and sudden death showed homogeneous presentation with regard to frequency. CONCLUSIONS: The causes of death during the acute phase of acute cerebrovascular disease are principally non neurologic (49%) being potentially preventable with the most frequent causes of death being from pneumonia, sepsis and pulmonary thromboembolism. Mortality of these patients may be decreased on correct diagnosis and treatment. PMID- 7799665 TI - [Stress and the cerebral blood flow]. PMID- 7799666 TI - [Health care according to the sex of patients]. PMID- 7799667 TI - [Vasculitis associated with a myelodysplastic syndrome: a report of 5 cases]. AB - In a study of 94 patients with myelodysplastic syndrome (MDS) associated vasculitis was observed in 5, which preceded hematologic diagnosis in 4. Leukocytoclastic vasculitis was observed in 5 cases being associated to lobular panniculitis in one. Three patients had refractory anemia, one sideroblastic anemia (SA) and another refractory anemia with excess blasts (RAEB). In the latter case lymphomatoid papulosis was also observed which, to date, has not been previously described in association with MDS. Another case presented seronegative polyarthritis and renal disease coinciding with vasculitis. Polyarteritis nodosa was diagnosed in a third patient in agreement with the criteria of the American College of Rheumatology, the association of which with MDS is exceptional. In the same case medullary cytogenetic study showed 46, XY,t (12;20), an abnormally which has not been described to date in cases of MDS. All the cases were treated with glucocorticoids in addition to cyclophosphamide in the patient with polyarteritis nodosa, with an improvement in the vasculitis being observed in all the patients. Two patients died, one (SA) due to pneumonia and the other (RAEB) due to subdural hematoma following transformation to acute myeloblastic leukemia. With 5% of the MDS studied presenting vasculitis, this syndrome should be included in the differential diagnosis of vasculitis observed in patients with cytopenia. PMID- 7799668 TI - [Malpractice accusations: causes, consequences and prevention]. PMID- 7799669 TI - [The basic treatment of arterial hypertension (I). Changes in life style and the control of risk factors]. PMID- 7799670 TI - [Lobular carcinoma in situ of the breast]. PMID- 7799671 TI - [The neuroleptic malignant syndrome]. PMID- 7799672 TI - [The neuroleptic malignant syndrome]. PMID- 7799673 TI - [The neuroleptic malignant syndrome]. PMID- 7799674 TI - [The neuroleptic malignant syndrome]. PMID- 7799676 TI - [The neuroleptic malignant syndrome]. PMID- 7799675 TI - [Hypocalcemia in a patient with the acquired immunodeficiency syndrome treated only with foscarnet]. PMID- 7799678 TI - [The usefulness of different markers in the diagnosis of advanced HIV infection]. AB - BACKGROUND: The aim of this study was to evaluate the usefulness of different markers to diagnose advanced infection by the human immunodeficiency virus (HIV) (AIDS or CD4 lymphocyte < 0.2 x 10(9)/L), establish the degree of correlation and define markers of advanced infection in primary health care. METHODS: Clinical, hematological, biochemical, cellular, serological and immunological variables were analyzed in 146 patients diagnosed for the first time with HIV infection. The patients were classified into three stages: A (II, III, CDC-1987), B (IV-A, IV-C2) and C or advanced (IV-C1, IV-D). The following data were compared: the results in the three stages, the degree of correlation, the specificity and sensitivity to the diagnosis of AIDS. Two multiple logistic regression models were established: the first for all the variables and the second for only those available in primary health care. RESULTS: All the markers except the triglycerides, IgG, IgM, and beta 2-microglobulin presented significant differences in the stages (p < 0.05). With the exception of the CD3+, CD4+ and CD8+ lymphocytes (r > or = 0.6 or -0.6) the remaining variables were independent. The decrease in CD4+ and the increase in neopterin were very sensitive markers (> 95%) but only hyperamylasemia demonstrated a specificity greater than 95% for the diagnosis of advanced infection. Oropharyngeal candidiasis (OR = 4.80) and the CD4+ lymphocyte (OR = 0.99) had the greatest weight in the first model. In the second model the most significant markers were weight loss (OR = 4.41), a decrease in lymphocytes (OR = 7.65) and an increase in IgA (OR = 5.82) with p < 0.01 and a predictive value of 85.16%. CONCLUSIONS: The presence of weight loss, lymphocyte count < 1 x 10(9)/L and an increase in IgA may be used in primary health care to diagnose advanced infection by the human immunodeficiency virus. Asymptomatic hyperamylasemia with no apparent cause suggests advanced infection. PMID- 7799677 TI - [Seroepidemiology of hepatitis C virus infection in pregnant women in Catalonia]. AB - BACKGROUND: The aim of this study was to investigate the prevalence of hepatitis C virus (HCV) infection in a population of pregnant women in Catalonia and the sociodemographic variables and risk factors associated to this prevalence. METHODS: A representative sample of the pregnant women in Catalonia (n = 4,551) randomly selected by clusters (hospitals with maternity clinics) was studied. Detection of antiHCV antibodies was performed by the third generation ELISA test. Reactive cases were confirmed with RIBA 3 and MATRIX. RESULTS: The prevalence of antiHCV was found to be 1% and was not significantly associated with any of the sociodemographic variables studied (age, social and cultural level, origin and residence). A history of blood transfusion, intravenous drug consumption and hepatitis in the sexual partner were the only risk factors associated with the prevalence of infection found on univariate analysis although these were only present in 47% of the antiHCV positive cases detected. The association between the positivity of antiHCV and the history of hepatitis in the partner was lost on stratification of the cases according to the possible existence of history of drug addiction. CONCLUSIONS: A high proportion of young asymptomatic people (1%) were found to have hepatitis C virus infection with the possible mode of infection not being detected in approximately half of these subjects. In the other half of these cases the infection was found to have been acquired by an intravenous mechanism: blood transfusion or drug use. PMID- 7799679 TI - [Isolation, sequencing and ultrastructure of HTLV-I and HTLV-II retroviruses. Presence of the HTLV-II subtype b among Spanish intravenous drug addicts]. AB - BACKGROUND: Six cases of HTLV-I/II infection were selected for isolation and characterization of these retrovirus. METHODS: Detection of anti-HTLV antibodies was carried out by enzyme immunoassay (EIA), immunofluorescence (IFI), and Western blot (WB). Analysis of proviral DNA was performed by PCR. Viral culture and partial sequencing of the pol and pX genes were carried out. Electron microscopy morphologically characterized the viral particles. RESULTS: Serologic study demonstrated four cases of HTLV-II, one of HTLV-I, and one non-typeable HTLV infections. This last case was confirmed as positive for HTLV-II by PCR. Five new HTLV-II and one HTLV-I infected cell lines have been established by co culture. Electron microscopy allowed morphologic characterization of the viral particles found in the infected cells. The sequence of the five strains of HTLV II was identical demonstrating a divergence of 0.49% in the pX region and of 4.5% in the pol region compared with the HTLV-II Mo prototype. Comparison of these sequences with those corresponding to different strains of HTLV-II isolates from American Indians (subtypes b) suggest that these Spanish strains are more closely related with the subtype b than with the subtype a (HTLV-II Mo). Genetic variability study did not reveal any change in the sequence of these stains suggesting that the variability of these retroviruses in very infrequent in the regions studied. The analysis of the pol region of the HTLV-I strain demonstrated a divergence of 3.4% with respect to the sequence of the ATK-1 prototype (Japan) and of 1.7% of the strain HS-35 (Caribbean) showing a greater relation with the Caribbean strains than with those from Japan. CONCLUSIONS: The presence of HTLV II subtype has been confirmed among intravenous drug addicts in Spain. Isolation and characterization of the HTLV-I strain demonstrated that this also circulating around Spain despite its South American origin. PMID- 7799680 TI - [Colchicine in the treatment of recurrent pericarditis]. PMID- 7799681 TI - [Medical-clinical audit (II). Definitions and typology]. PMID- 7799682 TI - [Evaluation and requirements of the HIV/AIDS test in pregnant women]. PMID- 7799683 TI - [31-Year-old male with recurrent oral aphthae, myopericarditis and arthritis]. PMID- 7799684 TI - [CD4+ lymphocytes and opportunistic infections and neoplasms in patients infected with the human immunodeficiency virus]. PMID- 7799685 TI - [CD4+ lymphocytes and opportunistic infections and neoplasms in patients infected with the human immunodeficiency virus]. PMID- 7799686 TI - I2C: a system for the indexing, storage, and retrieval of medical images by content. AB - Image indexing, storage, and retrieval based on pictorial content is a feature of image database systems which is becoming of increasing importance in many application domains. Medical image database systems, which support the retrieval of images generated by different modalities based on their pictorial content, will provide added value to future generation picture archiving and communication systems (PACS), and can be used as a diagnostic decision support tools and as a tool for medical research and training. We present the architecture and features of I2C, a system for the indexing, storage, and retrieval of medical images by content. A unique design feature of this architecture is that it also serves as a platform for the implementation and performance evaluation of image description methods and retrieval strategies. I2C is a modular and extensible system, which has been developed based on object-oriented principles. It consists of a set of cooperating modules which facilitate the addition of new graphical tools, image description and matching algorithms. These can be incorporated into the system at the application level. The core concept of I2C is an image class hierarchy. Image classes encapsulate different segmentation and image content description algorithms. Medical images are assigned to image classes based on a set of user defined attributes such as imaging modality, type of study, anatomical characteristics, etc. This class-based treatment of images in the I2C system achieves increased accuracy and efficiency of content-based retrievals, by limiting the search space and allowing specific algorithms to be fine-tuned for images acquired by different modalities or representing different parts of the anatomy. PMID- 7799687 TI - Worklists, preloading and archiving strategies; 3 years of clinical experience in the Barcelona PACS. AB - We present data on 3 years of clinical experience using PACS involving developments on worklists, preloading and archiving strategies in a teaching paediatric hospital with all modalities connected to a commercial PACS. A method allowing generation of and handling of different worklists for computed radiography examinations has been developed in our centre. Worklists and archiving strategies are presented and discussed. We conclude that, with adequate worklists and efficient preloading implementation, current PACS could be used successfully in several clinical settings of a multimodality department. PMID- 7799688 TI - A generic approach to the management of time-related signals and images in medicine. AB - A framework concept for design and implementation of medical workstations is described by (a) its underlying principles, (b) the handlers provided by the concept, (c) the available data structures and (d) the graphical user interface (GUI). The design principle takes care of a modular approach both for the framework and for the applications. The GUI provides a coherent look and feel for applications based on toolkits for displaying data objects and application control. The data handler allows management of n-dimensional data matrices in a multi-vendor environment, whereas the parameter handler takes care of the data object description. An implementation of a medical workstation exploiting the framework concept is presented. PMID- 7799689 TI - Multimedia E-mail systems for computer-assisted radiological communication. AB - In the film-based organization of communicating radiological results to the referring physician, the different media (text, images, graphics, voice) are separated. When using computer technology, multimedia reports containing links between these different media can be used. This changes the way radiological reports are generated, accessed, and possibly discussed. We performed experiments in a clinical setting using two different metaphors for communicating multimedia information. In the 'paper metaphor', labels in the report text are linked to annotations in selected images. In the 'slide presentation metaphor', annotated images are presented synchronously to a spoken report. With both systems additional interaction between radiologist and referring physician is supported using multimedia 'electronic mail'. The experiments indicate that multimedia does not only significantly increase the efficiency of information transfer, but also has the potential to make reporting itself more efficient. Given that the amount of image-related information keeps growing, multimedia links are a promising method to give efficient access to the most relevant information. PMID- 7799690 TI - Filmless digital radiology--feasibility and 20 month experience in clinical routine. AB - We present the clinical experiences of PACS based on 20 months routine operation of the first filmless radiology department worldwide. PACS planning and implementation strategies for potential vendors are discussed. The actual implementation status of this major teaching hospital with currently 560 acute care beds comprises three computed radiography systems, five digital fluoroscopic units, eight ultrasound machines, five mobile units, three angio suites and two CT's interconnected with a PACS, a RIS, which is coupled with three voice recognition systems for report generation during nights, and a HIS. Primary diagnosis is performed on 16 workstations with two to six high-resolution, high contrast monitors. Twenty-six peripheral viewing stations provide image display on the wards and in outpatient clinics. During the first 20 months 586.047 images have been acquired, resulting in 1.3 Tbyte of data stored on optical disks. Currently the daily data production is 5-6 Gbyte, the network traffic 15-18 Gbyte. Benefits of PACS primarily are reliable access to image information, speeding up report cycle time, which contributes to the reduction of the average patient length of stay (LOS). The LOS in our hospital is the shortest (6.4 days) of all Austrian hospitals. So it may be stated that PACS improves the quality of health care. PMID- 7799691 TI - Design for user efficiency in a dedicated ICU viewing station. AB - The intensive care unit (ICU) is one application where significant benefit is expected from the use of digital technology in the acquisition, management and presentation of images. However, the potential benefits should not be outweighed by disadvantages of current digital technology. One of the bottlenecks is the efficiency of image viewing using a workstation, especially if this viewing station is implemented using affordable commonly available hardware. In this paper we describe the design concepts of a relatively low-cost but efficient viewing station for chest images, and discuss clinical experience with this system at an ICU ward. The user interface has been optimized towards the specific patterns of ICU image viewing. By anticipating user requests and preparing images during idle times of the computer, the mean image access time could be reduced by a factor of 4, while most images could be presented instantaneously. Information from the hospital information system (HIS) is exploited in the user interface, and a simplified PAC-HIS coupling has been implemented for the simultaneous presentation of images and reports. PMID- 7799692 TI - PAPYRUS 3.0: DICOM-compatible file format. AB - This paper describes the PAPYRUS 3.0 file format based on the new DICOM 3.0 Standard which addresses the open interchange of medical images in files or on removable storage media. This specific implementation of the DICOM standard is intended as a generic solution for interchange of multi-modality medical images on removable media. It can also be used for convenient exchange of image data between different computer systems through industry standard file transfer mechanisms. Finally it can also be used for storage and archiving of medical image data in a DICOM-compatible format. PMID- 7799693 TI - PACER: a software tool for PACS decision makers. AB - This paper describes the development of the software package PACER as it evolved from a cost model to a software package for PACS decision making. PACER was developed as part of the TEASS topic from the EurIPACS project. EurIPACS is an EU subsidized project covering a wide area of PACS related research. The TEASS topic concerns the evaluation of prototype PACSystems in three European hospitals. PACER allows the user to evaluate costs of various PACS implementation scenarios and compare them to the costs of the current film based situation. Its cost calculation is based on a straight forward description of costs of a film based radiology department and of PACS. The PACER cost analysis can consider stepwise introduction of PACS and a corresponding stepwise disappearance of the film environment. This analysis includes effects of price developments. PACER calculates costs and expenses for a number of years in succession. The calculated results can be analysed using graphs, tables and sensitivity analysis tools. Preliminary tests in three hospitals indicate that PACER can indeed be a useful tool in the decision process concerning PACS. PMID- 7799694 TI - Legal aspects of digital image management and communication. AB - This paper outlines the legal issues that arise in digital image management and communication systems (IMACS). At the heart of this study is the digital image which is manipulated, processed, communicated, stored, compressed and archived, and which is difficult to ascertain from a legal point of view because of its intangible nature. On the one hand, personal data protection and the patient's right to privacy need to be protected through a data protection and security policy. This is particularly important in view of the capacity of IMACS to integrate with other systems such as HIS and RIS, since the information generated by the totality of these systems offers a very complete picture of any patient. On the other hand, the evanescent nature of the digital image creates legal uncertainties as to questions of evidence, of procedural and legal admissibility and acceptability and of liability. PMID- 7799695 TI - MIMOSA: a functional model of the management of medical images. AB - The concept of picture archiving and communication system (PACS) appeared in 1982. Twelve years later most PACS prototypes still do not satisfy the medical community requirements: too much emphasis has been put on technical solutions and little effort devoted to the management of images itself. A common approach to this problem is needed more than ever to allow cost-effective systems to be developed. Modelling is a way to reach this objective, and the MIMOSA topic within the AIM/EurlPACS project aims at defining such a model of medical image management. This paper presents the MIMOSA approach with the three underlying constraints, i.e. genericity, implementation independence and performance. The MIMOSA group is building three interrelated models: a data model, a functional model and a dynamic model. However, in this report we focus only on the functional model, and explain how it was abstracted from various clinical scenarios in the first phase of the project. The availability level concept is introduced as a customizable and implementation independent solution to the problem of managing the delay of access to the information. The so-called contextual diagram and the acquisition of a new examination which are two representative parts of the model are detailed. The validation aspects and the relationships to projects working on the management of patient records are addressed as a conclusion. PMID- 7799696 TI - Proceedings of the 11th International EuroPACS Meeting. Rennes, France, 30 September-2 October, 1993. PMID- 7799697 TI - Iodised salt in India. PMID- 7799698 TI - European medicines in the 21st century. PMID- 7799699 TI - Inhaled sodium cromoglycate in angiotensin-converting enzyme inhibitor cough. AB - Cough is a frequent side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the effects of inhaled sodium cromoglycate in 10 patients with ACE-inhibitor cough in a double-blind crossover study. After a 2-week run in, patients were randomised to either 2 weeks' inhaled sodium cromoglycate or placebo followed by a further 2 weeks on the other treatment. Patients kept a cough diary during each study period. Cough severity was recorded on a scale from 0 to 12. At the end of each study period the cough threshold to inhaled capsaicin was measured. 9 patients reported a reduction in cough after sodium cromoglycate. Median (range) daily cough scores during run-in and placebo periods were 3.6 (1.9 6.4) and 4.1 (0.6-8.1), respectively (p > 0.05). Median daily cough score after sodium cromoglycate was 1.8 (0.4-3; p < 0.01). There was a significant relation between initial cough severity and benefit from sodium cromoglycate; and cough reflex sensitivity to inhaled capsaicin was significantly reduced. Inhaled sodium cromoglycate is an effective treatment for ACE-inhibitor cough. Its effect may be due to suppression of afferent vagal activity. PMID- 7799701 TI - Asthma deaths in New Zealand: whodunnit? PMID- 7799700 TI - Plasma (1-->3)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. AB - (1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe crab coagulation enzyme that is extremely sensitive to this polysaccharide. With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon. Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients. PMID- 7799703 TI - Horizontal transmission of hepatitis B virus. AB - In 1991-92, a cross-sectional survey in Flanders (Belgium) for hepatitis B virus (HBV) markers among 277 relatives of institutionalised mentally handicapped persons to evaluate the prevalence of hepatitis B and the risk of infection showed that relatives of an HBV positive resident were 7.6 times more likely to be infected than relatives of an HBV seronegative mentally handicapped person. HBV infection among the family members could be attributed in 83% to exposure to an HBV positive resident. This study demonstrated the importance of horizontal transmission among relatives of institutionalised mentally handicapped people, even if family contact is reduced to weekend and holiday activities. We recommend that HBV vaccination policy should be expanded to include relatives of institutionalised mentally retarded people. PMID- 7799702 TI - Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma. AB - The helicobacter-associated transition from chronic gastritis to MALToma (lymphoma of mucosa-associated lymphoid tissue) may require genetic change in the host. We have studied gastrectomy specimens from twelve cases of primary B-cell gastric lymphoma showing evidence of chronic gastritis and low-grade or high grade MALToma to look for allele imbalance at microsatellites for six tumour suppressor genes. We detected allelic imbalance at two of these loci (DCC in three, APC in two). In two DCC cases allele imbalance was seen in the transition from chronic gastritis to low-grade MALToma and in the third between low-grade and high-grade. Allele imbalance between chronic gastritis and low-grade MALToma is not necessarily causal in the transition. Rather, genetic change has occurred in the process of transformation. PMID- 7799704 TI - Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer. AB - We treated 19 patients with advanced breast cancer resistant to tamoxifen with a new specific antioestrogen (ICI 182780) which, in animal studies, has no agonist activity. 13 (69%) patients responded (7 had partial responses and 6 showed no change) to monthly intramuscular injections of ICI 182780 after progression on tamoxifen, for a median duration of 18 months with minimum side effects. Preliminary evidence suggests that the agent is without effects on the liver or the hypothalamic-pituitary axis. ICI 182780 appears to be a promising new agent for treatment of advanced and early breast cancer. PMID- 7799705 TI - Glue ear: prescribe, operate, or wait? PMID- 7799706 TI - Vitamin A. PMID- 7799707 TI - Is laparoscopic hysterectomy a waste of time? AB - Laparoscopic hysterectomy (LH) is a way to avoid laparotomy. However, there is evidence that most women treated by abdominal hysterectomy are suitable for vaginal surgery. To test this hypothesis, and to determine the relative merits of laparoscopic and vaginal hysterectomy (VH) and the best technique for LH, we prospectively studied 98 women who had relative contraindications for vaginal surgery by traditional criteria. 75 underwent LH and 23 VH. The LH group included 22 women who had been assigned to this route of surgery as part of a prospective randomised controlled comparison with VH (23 women). Surgery was completed with the intended technique in 93.9% of cases. 5 women in the LH group (6.7%) and 2 in the VH group required laparotomy or additional procedures. In the prospective randomised study LH took longer than VH (mean duration 131 vs 77 min). VH was the faster procedure, irrespective of uterine size and need for oophorectomy. With LH, the operative time increased as more of the hysterectomy was carried out with laparoscopic rather than vaginal dissection. Complication rates, blood loss, analgesia requirements, and recovery were similar for the two techniques. Our study confirms that most hysterectomies could be performed vaginally, and that LH is a much slower procedure. If LH is done, it should be converted to a vaginal procedure as early as possible to reduce the overall operating time. LH does seem to be a waste of time for most patients. PMID- 7799708 TI - Risk of relapse in multibacillary leprosy. PMID- 7799710 TI - Drunken drivers beat a retreat. PMID- 7799709 TI - End of the New Zealand asthma mortality epidemic. AB - In 1989, a case-control study reported that inhaled fenoterol was associated with the epidemic of asthma deaths that had affected New Zealand since 1976. The New Zealand Department of Health issued warnings about the safety of fenoterol and restricted its availability. The associated time trends are consistent with the hypothesis that fenoterol was the main factor in the New Zealand asthma mortality epidemic. The epidemic commenced when fenoterol was introduced in 1976, and the New Zealand death rate remained the highest in the world for more than a decade. After publication of the case-control study, the death rate fell by half and has now remained low for a further 3 years (1990-92). Time-trend data do not suggest a class effect of inhaled beta-agonists in the epidemic: there was no association between beta-agonist sales and the start of the epidemic, and total sales of inhaled beta-agonists actually increased slightly during 1989-90 when the epidemic came to an end. Time-trend data are also inconsistent with the hypothesis that the epidemic may have occurred because of underprescribing of inhaled corticosteroids. Similarly, time-trend data is incosistent with hypotheses postulating a major role of social factors such as unemployment. Data on time trends should be assessed with caution, because time trends in asthma deaths can be affected by many factors. Nevertheless, the New Zealand time trends are consistent with fenoterol being the main cause of the New Zealand asthma mortality epidemic and are inconsistent with a significant role for other suggested causes. PMID- 7799711 TI - Pelvic exenteration: by whom and for whom? PMID- 7799712 TI - Deconstructing vulval pain. PMID- 7799713 TI - Safety and transcervical endometrial resection. PMID- 7799714 TI - Safety and transcervical endometrial resection. PMID- 7799715 TI - Safety and transcervical endometrial resection. PMID- 7799716 TI - Termination of trial of streptokinase in severe acute ischaemic stroke. MAST Study Group. PMID- 7799717 TI - Anticoagulant monitoring with transcranial Doppler. PMID- 7799718 TI - Iron status in Still's disease. PMID- 7799719 TI - Is Still's disease associated with parvovirus B19 infection? PMID- 7799720 TI - When to use fluconazole. PMID- 7799721 TI - Screening for codon 249 p53 mutation in lung cancer associated with domestic radon exposure. PMID- 7799723 TI - Routine chest radiographs in admissions to coronary care. PMID- 7799722 TI - Reversal of brain metabolic alterations with zidovudine detected by proton localised magnetic resonance spectroscopy. PMID- 7799724 TI - Aromagram for antibiotic activity. PMID- 7799725 TI - ECT and young minds. PMID- 7799726 TI - Placebos in medicine. PMID- 7799727 TI - Placebos in medicine. PMID- 7799728 TI - In-vitro fertilisation and health care coverage. PMID- 7799729 TI - Clustering of childhood peritoneal mesothelioma in the Midlands, UK. PMID- 7799730 TI - Intravascular line infection with Exophiala dermatitidis. PMID- 7799731 TI - Acute and recurrent airflow obstruction after exposure to artificial fog. PMID- 7799732 TI - Apolipoprotein E in Creutzfeldt-Jakob disease. PMID- 7799733 TI - Apolipoprotein E in Creutzfeldt-Jacob disease. PMID- 7799734 TI - Simultaneous outbreak due to Vibrio cholerae and Shigella dysenteriae in Kenya. PMID- 7799735 TI - Fat-soluble vitamins. PMID- 7799736 TI - Immunity to pneumococcal infections. PMID- 7799737 TI - Antibodies to HTLV-I in Sjogren's syndrome. PMID- 7799738 TI - Antibodies to HTLV-I in Sjogren's syndrome. PMID- 7799739 TI - Antibodies to HTLV-I in Sjogren's syndrome. PMID- 7799740 TI - Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus related lymphoproliferation. AB - Reactivation of Epstein-Barr virus (EBV) after bone-marrow transplantation leads in many cases to lymphoproliferative disease that responds poorly to standard therapy and is usually fatal. To prevent or control this complication, we prepared EBV-specific cytotoxic T-lymphocyte (CTL) lines from donor leucocytes and infused them into ten allograft recipients. Three of the patients had shown signs of EBV reactivation, with or without overt lymphoproliferation, and the others received CTL infusions as prophylaxis. No patient developed any complication that could be attributed to the CTL infusions. In the three patients with EBV reactivation, EBV DNA concentrations (measured by semiquantitative polymerase chain reaction [PCR]), which had increased 1000-fold or more, returned to the control range within 3-4 weeks of immunotherapy. The most striking consequence was the resolution of immunoblastic lymphoma in a 17-year-old patient who received four CTL infusions (two 1 x 10(7)/m2 and two 5 x 10(7)/m2). Because the CTL had been genetically marked before infusion, we were able to show by PCR analysis that they persisted for 10 weeks after administration. EBV-specific donor-type T-cell lines seem to offer safe and effective therapy for control of EBV-associated lymphoproliferation. PMID- 7799742 TI - Determination of efficient parameters for argon laser-assisted anastomoses in rats: macroscopic, thermal, and histological evaluation. AB - The aim of this study was to determine efficient parameters for an argon laser (spot diameter = 200 microns) to obtain and reproduce vessel anastomoses. It was performed in two groups of Wistar rats. In the first group (89 Laser impacts on 10 carotids), the fluence was continuously adjusted from 30 to 3,000 J/cm2 in order to determine efficient sets of parameters (power from 90-200 mW, pulse duration from 0.1 to 5 seconds, pulsed or continuous mode). In the second group, 30 end-to-end carotid anastomoses were performed. The results were evaluated by macroscopic thermal, and histological studies. The second group proved the efficiency of the selected parameters. Vessel welding was obtained with 100 mW, 3 seconds, continuous mode (fluence = 950 J/cm2, irradiance = 320 W/cm2) for a mean temperature of 77 degrees C corresponding to collagen denaturation. In the second group the patency rate was 93% (28/30) with three pseudo-aneurisms and two thromboses. Histological studies noted slight modifications of the media. PMID- 7799741 TI - Lasers in neurosurgery. AB - Lasers have been used in neurosurgery for the past 25 years, undergoing modifications to suit the specific needs of this medical discipline. The present report reviews the current use of lasers in neurosurgical practice and examines the pros and cons of lasers in specific neurosurgical applications. In spite of their advantages, laser use is still not widespread in neurosurgery. One reason is the continued lack of complete control over real-time laser interactions with neural tissue. A greater acceptance and use of lasers by neurosurgeons will depend upon automated control over defined specific parameters for laser applications based upon the type of tissue, the desired effect on tissue, and application to the clinical situation without loss of precision and a lot of expense. This will require the integration of newer lasers, computers, robotics, stereotaxy, and concepts of minimally invasive surgery into the routine management of neurosurgical problems. PMID- 7799743 TI - Rate process model for arterial tissue thermal damage: implications on vessel photocoagulation. AB - A numerical model for thermal damage to human arterial tissue is presented, based on protein denaturation kinetics. The model involves determination of coefficients of rate processes A & delta E, which are tissue type-dependent (arterial tissue in this study), and definition of threshold damage. A feedback controlled constant surface temperature device was used to induce 80 coagulative lesions of arterial human tissue ranging in temperature from 66 degrees C to 76 degrees C and in duration from 15 to 1,500 seconds. The measured coefficients were determined to be A = 5.6 x 10(63) s-1 and delta E = 430 KJ mole-1. These numerical values closely approximate the coefficients of the rate process for denaturation of collagen molecules. These and other histological observations strongly suggest collagen to be the primary coagulating component of arterial tissue at the onset of thermal coagulative damage. The ability of this model to predict onset of tissue coagulation during laser coagulation was studied using 10 postmortem human arterial samples exposed to argon laser irradiation. PMID- 7799744 TI - Continuous measurement of the heat-induced changes in the optical properties (at 1,064 nm) of rat liver. AB - The radiative transfer optical properties (absorption coefficient, scattering coefficient, and anisotropy of scattering) of slowly heated rat liver have been measured at 1,064 nm. Continuous measurements were made using double-integrating spheres and collimated illumination of the sample for up to 5,000 seconds heating with equilibrium temperatures of 48 degrees, 52 degrees, and 58 degrees C. Generally, the scattering increased, and the absorption and anistropy decreased at rates dependent on the heating temperatures. However, there was a large variability between samples. PMID- 7799745 TI - Trends in health policy: heading home. PMID- 7799746 TI - [Improvement of effectiveness of high frequency electrosurgical equipment]. AB - The paper summarizes the results of the activities of the All-Russian Research Institute of Medical Industry on the development of electric stimulating equipment for anesthesiology and the experience in its application. It also deals with electrostimulations, such as transcranial (transcerebral) electroanalgesia, transdermal (transcutaneous) electroneurostimulation, epidural (peridural) electrostimulation, perineural electric neurostimulation, testing electrostimulation of peripheral nerves in making regional anesthesia, electric neurostimulating testing of neuromuscular transmission. The developed monofunctional Delta-101, Delta-102, Delta-301, Synapse-1 electric neurostimulators and a polyfunctional Anestim-PF apparatus used in anesthesiological care and other related medical fields. PMID- 7799747 TI - [Electric nerve stimulation devices in anesthesiology: research and development]. PMID- 7799748 TI - [Optic unification of rigid medical endoscopes]. PMID- 7799750 TI - [Improvement of technical knowledges of scientists and laboratory physicians in the field of radionuclide microanalysis]. PMID- 7799749 TI - [Development of new ultraviolet therapy equipment for phototherapy]. AB - The papers deals with the development of phototherapeutical ultraviolet radiation equipment, outlines the design and basic data of five new phototherapeutical radiation sources developed in the Laboratory of Medical Radiation Sources, VNIIMP-VITA joint stock company. PMID- 7799751 TI - [Computerized spirometers (analysis of problem solving)]. AB - The basic constructive and algorigthmic designs which are widely used in the up to-date national computers to measure forced expiration parameters are analysed. The most frequently encountered circuits and basic metrological parameters are given and testing procedures are outlined. PMID- 7799752 TI - [Choice of equipment for the diagnosis of lung diseases]. AB - The paper substantiates the principle of functional auxiliaries which ensure formation of mono- and polyfunctional devices from interchangeable functional elements (modules or units): universal, general for all apparatuses, as well as an auxiliary, specialized for one or some procedures, each devices being centralized in the universal element. PMID- 7799753 TI - [Systematic aspects in designing equipment for psychophysiological evaluation]. PMID- 7799754 TI - [Systematic basis of analysis of action sequences in a "Binatest" device]. AB - The paper presents a method for analysing and interpreting the results of patients' examination using a Binatest device. The examination was made in the situation of "optional choice" wherein multiple acts of choice from two alternative goal-oriented reactions lead only to positive results. The proposed analysis is based on the evaluation of previous quanta of behavior for further goal formation with limited analysis depth with three sequential events. The paper discusses what information may be derived from the analysis of monads, diads, and triads of step-by-step acts of choice. Four major parameters fit for the analysis and interpretation of the findings have been identified. These include diad asymmetry, runs, left and right stereotypies. Each parameter has its own value that is orthogonal towards the others, equal measurement limits, which are independent of their production, and fully determines the sequence of behavioral quanta at the depth of 3 events. It is shown that basic information on decision-making should be searched in the structure of sequential choice acts made by a patient during his/her examination rather than in the chosen behavioral acts themselves. PMID- 7799755 TI - [Local preventive antibacterial therapy with polymer biocompatible combination]. AB - The paper provides data on the properties of the powdery antimicrobial absorbent Ambipor and the procedure of its use in the prevention of postoperative suppuration, which consists in application of the powder to the wound surface with a broken layer just before wound suture. It shows that a single application of Ambipor to wound suture. It shows that a single application of Ambipor to wound tissues at the end of an operation ensures high paravulnar tissue antibiotic concentrations which are many times higher those used in conventional antibacterial therapy. Implantation of Ambipor to operative wound tissue at the end of an operation aids to reduce the extent microbial dissemination by more than 100-1000 times, to accelerate reparative processes, stimulate early fibroplast activation, fibrillogenesis, scarring tissue maturation. Topical antibacterial therapy with the developed formulations is an effective tool in preventing postoperative wound complications. Its application to clinical practice enables the incidence of complications to be decreased by more than 4.5 times higher than those in the controls. PMID- 7799756 TI - [Medical equipment and devices the International exhibition "Public Health-93" (review of exhibition)]. PMID- 7799757 TI - [Basic problems and development of technical level in medical instruments industry]. PMID- 7799759 TI - [Functional complementarity methods in the artificial life support equipment]. PMID- 7799758 TI - [Biocompatible polymer implants in the pediatric orthopedics]. PMID- 7799760 TI - The medical care of competitive athletes: the role of the physician and individual assumption of risk. PMID- 7799761 TI - Efficacy of magnetic resonance imaging of the elbow. AB - Elbow dysfunction is usually related to acute or chronic injury to the soft tissue components of the elbow. Prior to the development and application of magnetic resonance imaging (MRI), radiologic evaluation of the elbow was primarily limited to the detection of osseous abnormalities. The value of MRI to accurately determine the nature and extent of the pathologic changes in ligaments, tendons, muscles, and the osseous structures of the elbow joint is presented in the following discussion. PMID- 7799762 TI - Clinical biomechanics of the elbow in tennis: implications for evaluation and diagnosis. AB - Elbow injuries constitute a sizeable percentage of tennis injuries. Biomechanical analysis of the forces, loads, and motions on the elbow in tennis, and the constraint systems operating the control the forces, can lead to an understanding of the pathophysiology of these injuries. A biomechanically based evaluation framework can be used to document all of the clinical symptoms, anatomic alterations, and biomechanical alterations that are associated with the pathological problem. PMID- 7799763 TI - Wrist problems in the tennis player. AB - Although wrist injuries in tennis may occur from acute direct trauma, most injuries occur due to chronic overuse. Wrist biomechanics in tennis indicate that a wide range of wrist motion may not be necessary for effective play. The nature of the injury should be established as early as possible with the goals of restoring the wrist to a pain-free stable unit with normal range of motion. A secondary goal is to return the athlete to play as quickly as possible. Key points of the athlete's history are acute or chronic onset, progressive symptoms, and severity of symptoms, i.e., limitation of play. Key points of the physical examination include localization of maximal tenderness, edema, loss of range of motion, and bilateral grip strength. Plain roentgenograms should always be obtained. Specific imaging studies may be indicated and include bone scan, computed tomography, and arthrography. Specific and common wrist tennis injuries are discussed and treatment recommendations are given. Wrist problems in tennis are no uncommon and are responsible for a significant amount of lost playing time. Familiarity with the more common problems will enhance the physician's ability to evaluate and treat these athletes. PMID- 7799764 TI - Catecholamine response to exercise and training in individuals with spinal cord injury. AB - It is unknown whether the catecholamine (CAT) response to acute exercise and prolonged training in humans with spinal cord injury (SCI) is similar to that of neurologically intact man. Plasma samples were collected from seven subjects with chronic SCI (level of injury C5-T7) at rest and during voluntary arm-crank ergometry (ACE) before and after 6 months of training with functional electrical stimulation cycle ergometry (FES-CE). Similar plasma collections were made during one FES-CE exercise training session after 6 months of training. Norepinephrine (NE) and epinephrine (EPI) were measured by HPLC. After FES-CE training, resting NE decreased 37% (950 +/- 150 vs 1510 +/- 350 pmol.l-1 pretraining); resting EPI decreased 80% (54 +/- 10 vs 163 +/- 32 pmol.l-1 pretraining) (P < 0.05 by paired t-tests). No significant changes were observed in group means after training for the CAT response to submaximal ACE; however, five of seven subjects exhibited greater increments in plasma NE with ACE after FES-CE training. Acute FES-CE exercise elicited a 55-844% increase in NE, and a 35-350% increase in EPI above resting values with power outputs eliciting heart rates of 90-146 bpm. These data provide evidence for a systemic CAT response in subjects with SCI during acute FES-CE and reduced resting CAT following 6 months of training with FES-CE. PMID- 7799766 TI - Altered control of calcium in coronary smooth muscle cells by exercise training. AB - The increase in myoplasmic free Ca (Cam) is a primary trigger of contraction in vascular smooth muscle. We review data showing that the sarcoplasmic reticulum (SR) can buffer (attenuate) increases in Cam by: 1) sequestering a fraction of Ca entering the cell via sarcolemmal influx pathways, and 2) slowly releasing Ca from the SR toward the sarcolemma for extrusion from the cell, thereby decreasing subsequent agonist-induced Cam transients and contraction--so called "SR Ca unloading." Endurance exercise trained (EX), not sedentary (SED), Yucatan miniature pigs show SR Ca unloading via a ryanodine-sensitive SR Ca release pathway. The slow release of Ca from SR of EX cells may allow for efflux from the cell by close functional association with sarcolemmal Ca efflux mechanisms. In contrast, rapid, bolus release and resequestration of Ca by the SR of SED cells prevents Ca efflux from the cell. The endothelin-sensitive SR Ca store, a subset of the caffeine- and ryanodine-sensitive SR, is decreased in EX cells. Mildly increased resting Cam in EX cells may reflect a constant leak of Ca from the SR. The endothelin-sensitive SR Ca store was loaded above basal levels by depolarization-induced Ca influx. Collectively, these data indicate altered Cam regulation by the SR in coronary artery of EX animals. Future studies should focus on the molecular mechanisms of altered Cam regulation. PMID- 7799765 TI - The effects of gymnastics training on bone mineral density. AB - The purpose of this study was to examine the effect of 27 wk of gymnastics training on bone mineral density (BMD), body composition, insulin-like growth factor I (IGF-I), and osteocalcin. Subjects were 11 female intercollegiate gymnasts and 11 controls. Dual energy x-ray absorptiometry (Lunar DPX) was used to determine BMD (L2-L4 and femur) and to assess body composition. The gymnasts were significantly lower in weight (53.9 and 60.8 kg) and % body fat (22.6 and 30.6) compared with controls. After training, body weights of gymnasts remained the same but there was a significant increase in lean tissue mass of 2.9 kg (6.7%, P < 0.05). No changes in body composition were observed in the controls. The gymnasts had significantly higher mean lumbar (1.321 vs 1.225), and femoral neck (1.163 vs 1.079) BMD (g.cm-2) than the controls. Lumbar BMD increased significantly (1.3%) in gymnasts following training but femoral neck BMD did not increase. No BMD changes occurred in the control group. Regarding serum IGF-I, no differences were seen between the groups or across time. Serum osteocalcin values were significantly higher in the gymnasts than the controls, but no differences were found across time. In conclusion, gymnasts had significantly higher BMDs than controls, and a significant increase in lumbar BMD was seen in the gymnasts following 27 wk of training. PMID- 7799767 TI - Exercise training-induced increase in coronary transport capacity. AB - The objective of this study was to measure effects of exercise training on coronary flow heterogeneity, microvascular transport, and hemodynamics. Five miniature swine were trained on a treadmill (ET) for 16 wk; five control pigs (C) were confined to cages for the same period. At the end of that period we used the multiple indicator dilution method to measure permeability-surface area product (PS) to EDTA over a range of flow (F) in an anesthetized, open-chest preparation. We found that the heterogeneity of flow as measured by microspheres decreased with increasing F, but that ET had no clear effect on heterogeneity. We evaluated PS from the indicator concentration curves, taking into account flow heterogeneity and variations in capillary recruitment throughout the bed. In both C and ET pigs we observed an increase in PS with F until a maximum value of PS was reached at full recruitment. This relationship between PS and F was unaltered by ET. However, hemodynamic resistance was significantly reduced by ET, and F was higher at a given perfusion pressure after training. Since PS increases with F, ET pigs had higher PS values at typical coronary artery pressures. PMID- 7799768 TI - Effects of exercise training on regulation of tone in coronary arteries and arterioles. AB - A large number of studies now support the concept that exercise training alters functional control of the coronary circulation. Recent work has approached this area using ex vivo coronary arterial preparations (proximal coronary arteries, near-resistance arteries, resistance arterioles) isolated from exercise-trained animals and contracting independently of confounding in vivo influences. The combined results of these studies indicate that training-induced alterations in vascular control mechanisms do not occur uniformly throughout the coronary vascular tree. Proximal epicardial coronary arteries (approximately 2.0 mm diameter) isolated from exercise-trained pigs exhibited significantly reduced contractile responsiveness to the alpha-adrenergic receptor agonist, norepinephrine, but unaltered contractile responsiveness to K+, acetylcholine, and endothelin. Also, proximal arteries from exercise-trained animals demonstrated enhanced sensitivity to the vasodilator effects of adenosine. At the other end of the vascular spectrum, in resistance arterioles (< 150 microns diameter) the relaxation responses to adenosine were unaffected by exercise training, but bradykinin-induced vasodilation (endothelium-dependent) was significantly enhanced. In near-resistance arteries (150-240 microns diameter) responses to both bradykinin and adenosine were enhanced by exercise training. Thus, exercise training is associated with intrinsic vessel size-dependent alterations in coronary smooth muscle and endothelium-mediated regulatory mechanisms. PMID- 7799769 TI - Clinical significance of coronary vascular adaptations to exercise training. AB - Coronary vascular adaptations to exercise training have been extensively studied at the microscopic level in animals and correlated with direct and indirect measurements of myocardial blood flow in patients with coronary artery disease. Animals have permitted more extensive study. These findings have generally supported an increased blood flow to the myocardium with exercise training. However, consistent positive structural and functional adaptations to training have not been observed in large animals. Clinical studies have been limited by methodological problems related to techniques for detecting ischemia and measuring myocardial blood flow and the variability in exercise stimulus. Well established ischemia and high-intensity, long-duration training were the factors that promoted vascular growth in exercising patients with coronary artery disease. Animals studies also have demonstrated the necessity for myocardial ischemia to be present to induce coronary collateral development with exercise training. Optimal promoters of vascular growth in patients with coronary disease may consist of pharmacological interventions combined with exercise training. PMID- 7799770 TI - Gastric emptying of ingested solutions in man: effect of beverage glucose concentration. AB - The purpose of this study was to compare the rate of gastric emptying of 20 g.l-1 (2G), 40 g.l-1 (4G), and 60 g.l-1 (6G) glucose solutions with that of water (W). On separate occasions in randomized order, a 600-ml test solution was instilled into the stomach of each of six healthy male volunteers. Gastric emptying was measured at 10-min intervals for 1 h by a double sampling gastric aspiration method that allowed the volume of test drink and of the gastric secretion present in the stomach to be measured at each time point. All solutions emptied rapidly and followed an exponential emptying pattern. The 20 g.l-1 glucose solution was emptied at the same rate as water. After the first 10 min of rapid emptying, 4G and 6G were emptied slower (P < 0.05) than water. 6G delivered more (P < 0.05) glucose to the small intestine than 4G, and 4G delivered more glucose than 2G. The results indicate that a 20 g.l-1 glucose solution has no effect on gastric emptying compared with water, but that after the first 10 min of rapid emptying, glucose solutions at a concentration of 40 g.l-1 or more delay gastric emptying. PMID- 7799771 TI - Androgen turnover during marathon running. AB - The purpose of the study was to investigate the effect of prolonged physical stress on peripheral androgen turnover. Venous blood samples were taken from 18 athletes 24 h before finishing a competitive marathon run and directly after running the race. Serum cortisol, testosterone (T), dehydroepiandrosteronesulfate (DHEAS), sex hormone binding globulin (SHBG), and 5 alpha-androstane- 3 alpha, 17 beta-diolglucuronide (3 alpha-AdiolG) were determined and corrected for hemoconcentration. Marathon running caused a rise in serum cortisol concentration in all athletes. Furthermore, a significant (P < 0.01) rise in serum T and T index (index of free T) was observed. The significant (P < 0.01) rise in serum DHEAS concentration, a mainly adrenal cortical androgen, pointed toward a stimulation of the adrenal cortex or a reduced hepatic metabolic clearance rate. Finally, 3 alpha-AdiolG, an androgen metabolite exclusively formed in peripheral tissues, was increased in the sera of all athletes. These results suggest that marathon running leads to increased concentrations of serum adrenal and gonadal androgens. The simultaneously increased 3 alpha-AdiolG levels may be caused by increased androgen turnover in peripheral tissues containing 5 alpha-reductase. PMID- 7799772 TI - Heart rate responses during a 4-d cycle stage race. AB - The purpose of this study was to monitor the heart rates (HR) of seven, well trained (maximal oxygen uptake [VO2max] 5.0 +/- 0.5 l.min-1), competitive cyclists during a 4-d cycle stage race. On consecutive days, subjects competed in a 16.0-km individual time trial (TT), a 110.0-km mass-start road race (RR1), a 5.5-km individual hill climb (HC), and a 105.0-km mass-start road race (RR2). Within 10 d of the final race, cyclists underwent a test to determine VO2max, peak power output, and maximal HR. Comparison of the HR responses to each race revealed that the individual events were performed at a relatively high and constant work rate (91.1 +/- 2.5% and 93.2 +/- 4.7% of the maximal HR as measured in the field (HRmax) for the TT and HC, respectively). In contrast, despite similar racing speeds (42.2 +/- 1.0, 39.9 +/- 0.2, and 40.6 +/- 0.5 km.h-1 for the TT, RR1, and RR2, respectively), the HR responses to the longer mass-start races were reduced to 81.9 +/- 9.6% and 78.6 +/- 8.9% of HRmax and were random in frequency and amplitude. Such stochastic changes in HR were seemingly unrelated to course terrain but may be due to the group dynamics of the cyclists. The results of this study reveal the stochastic nature of bunch cycle racing and show that the HR responses of competitive cyclists are more a function of tactical bunch riding than of terrain. PMID- 7799773 TI - Physiological comparison of uphill roller skiing: diagonal stride versus double pole. AB - The physiological responses to treadmill roller skiing with the double pole (DP) and diagonal stride (DS) techniques were compared at 1.7% and 7.1% grades among eight cross-country ski racers. Oxygen uptake (VO2) requirements were found to be lower (P < 0.05) for DP at the 1.7% grade, but similar at the 7.1% grade. In contrast, ratings of perceived exertion (RPE) and percentages of technique specific peak VO2 were similar between techniques at the 1.7% grade, and lower (P < 0.05) for DS at the 7.1% grade. RPE and percentages of technique-specific peak VO2 were strongly correlated (r = 0.89). The primary findings indicate that 1) the economies for DP and DS are dependent upon the incline, 2) it is possible for the economy of DP to be greater than DS although the percentages of technique specific peak VO2 are similar, and 3) the perceived effort associated with the use of DP and DS reflects the percentage of technique-specific peak VO2. PMID- 7799774 TI - Influence of rapid weight gain after the weigh-in on success in collegiate wrestlers. AB - We investigated whether acute weight gain between the weigh-in and competition was associated with success in a collegiate wrestling tournament. Wrestlers at the NCAA championships were weighed at the official weigh-in and again just before the first round of the tournament (20 h later). Weight gain and the weight discrepancy between first-round opponents were calculated (N = 607 excluding heavyweights). Indices of success included season record (% wins in total matches), tournament seeding, the sum of the advancement and placement points scored during the tournament (team points), and final placement in the tournament. ANOVA showed no differences in weight variation between placewinners and non-placewinners, or across placewinners only. Correlation coefficients among weight variables and indices of success were also low (P > 0.05). Multiple logistic regression, used to determine whether weight gain or weight discrepancy between opponents contributed to success in the first round of the tournament, revealed that neither variables was predictive of first-round outcome even after attempting to account for differences in ability (e.g., forcing team points into the regression first). CONCLUSION: neither acute weight gain after the weight-in or the weight discrepancy between opponents in the first round influenced success in a collegiate wrestling tournament. PMID- 7799776 TI - 26th Bethesda Conference: recommendations for determining eligibility for competition in athletes with cardiovascular abnormalities. January 6-7, 1994. PMID- 7799777 TI - Heterotrimeric G-protein effectors. PMID- 7799775 TI - Physical activity and hypertension. PMID- 7799778 TI - Transient expression assays for mammalian adenylyl cyclases. PMID- 7799779 TI - Specific peptide probes for G-protein interaction with effectors. PMID- 7799780 TI - Assays for G-protein regulation of phospholipase C activity. PMID- 7799781 TI - Chloride current assay for phospholipase C in Xenopus oocytes. PMID- 7799782 TI - Use of cytosol-depleted HL-60 cells for reconstitution studies of G-protein regulated phosphoinositide-specific phospholipase C-beta isozymes. PMID- 7799783 TI - Purification of phosphatidylinositol transfer protein from brain cytosol for reconstituting G-protein-regulated phosphoinositide-specific phospholipase C-beta isozymes. PMID- 7799785 TI - Purification of G-protein-regulated phospholipase C from turkey erythrocytes. PMID- 7799784 TI - Stimulation of phospholipase C by G-protein beta gamma subunits. PMID- 7799786 TI - Phospholipase C activity in Dictyostelium discoideum using endogenous nonradioactive phosphatidylinositol 4,5-bisphosphate as substrate. PMID- 7799787 TI - Purification of phospholipase C-beta 3 from rat brain. PMID- 7799790 TI - Amplification of phosphatidylinositol-specific phospholipase C-beta isoforms using degenerate primers. PMID- 7799789 TI - Purification of 110 kDa phosphoinositide phospholipase C activated by G-protein beta gamma subunits. PMID- 7799788 TI - Characterization of phospholipase C isozymes in bovine retina: purification of phospholipase C-beta 4. PMID- 7799791 TI - Analysis of guanine nucleotides associated with protooncogene ras. PMID- 7799792 TI - Measuring activation of kinases in mitogen-activated protein kinase regulatory network. PMID- 7799793 TI - Transcriptional activation analysis of oncogene function. AB - Because no single assay provides a complete analysis of the transformed phenotype, transactivation assays complement the cell growth and tumorigenicity analyses of oncogene function. Transactivation of ORE-containing genes is such a common feature of a diverse variety of viral and cellular oncogenes that it can be considered one aspect of the oncogene-induced phenotype. After the initial identification of oncogenes that activate transcription, studies of the mechanisms of activation and the identification of the downstream target genes should lead to a better understanding of the events leading to cellular transformation. The fact that cell type specificity of transactivation and transformation can be similar means that the transactivation assay may be a useful tool in dissecting cell type-specific transformation. The transactivation assay of oncogene function also has the advantage that it is easy to perform and significantly more rapid than assays based on altered cell growth. This is of particular advantage when one wishes to examine the function of a large number of oncogene mutants generated in vitro. Overall, transactivation assays provide another tool for examining transforming potential and a starting point for the analysis of the downstream targets of oncogenes. PMID- 7799794 TI - Biological assays for cellular transformation. AB - A number of standard and widely applied procedures have been used to determine whether expression of a particular gene triggers the growth alterations that are characteristic of most oncogenes. The assays have been used extensively to evaluate the transforming potential of a wide variety of genes that encode tyrosine or serine/threonine kinases, small and heterotrimeric GTP-binding signal transduction regulators, and nuclear transcription factors, among others. Therefore, the growth-promoting characteristics of a particular gene can be compared with the properties of other genes that have been characterized by the same assays. The assays described do not represent a complete evaluation of the transforming activity of a gene. Failure to detect growth-promoting activity in any of the assays does not definitively eliminate the possibility that a particular gene is an oncogene. Specialized assays that use (nonfibroblast) recipient cells more closely approximating the likely environment of the gene of interest may provide better approaches for subsequent studies. Other biological assays for transforming potential include measurements of the adhesion properties of cells on different substrata, the ability to grow on confluent monolayers of normal cells, the ability to invade into various artificial tissue matrices, and transgenic animal models. Finally, more specific assays for biochemical alterations that reflect the transformed state can also be employed. For example, as discussed in [23] in this volume, one widely used biochemical measure of transforming potential employs transcriptional activation of genes whose promoters contain so-called oncogene-responsive elements. This, as well as other biochemical assays, can be applied to complement the biological studies described in this chapter. PMID- 7799795 TI - Monitoring of receptor-mediated changes in intracellular calcium at the cellular and subcellular level by microfluorimetry and imaging. PMID- 7799796 TI - Purification of bovine retinal cGMP phosphodiesterase. PMID- 7799797 TI - Combination of microfluorimetric monitoring of cytosolic calcium and pH with patch clamp electrophysiological recordings in neutrophil granulocytes. PMID- 7799798 TI - Determination of adenylyl cyclase catalytic activity using single and double column procedures. PMID- 7799800 TI - Purification and reconstitution of N-type calcium channel complex from rabbit brain. PMID- 7799799 TI - G-protein-mediated pathways assayed by electrophysiology and confocal microscopy. PMID- 7799801 TI - Whole-cell patch recording in brain slices. PMID- 7799802 TI - Regulation of potassium channels by G-protein subunits and arachidonic acid metabolites. PMID- 7799804 TI - Regulation of Ca(2+)-sensitive adenylyl cyclases by calcium ion in vitro and in vivo. PMID- 7799803 TI - Preparation and use of "P"-site-targeted affinity ligands for adenylyl cyclases. PMID- 7799805 TI - Gi assays in transfected cells. PMID- 7799807 TI - The health care crisis: end or beginning of the heyday of medical decision support systems? PMID- 7799806 TI - Expression and purification of recombinant adenylyl cyclases in Sf9 cells. PMID- 7799808 TI - Health information, the fair information principles and ethics. AB - If advanced electronic patient records are construed as epistemic patient analogues in information space, then the traditional property-model of patient records is longer appropriate. A new paradigm is required. This paper suggests a new paradigm, examines its ethical implications and explores ways in which these could be reflected in legal and regulatory mechanisms. Special attention is paid to privacy, security and access relative to the so-called "fair information principles". PMID- 7799809 TI - Comments on: health information, the fair information principles and ethics. PMID- 7799810 TI - In search of rules for confidentiality: a critique of one proposal. PMID- 7799811 TI - Integrated Advanced Medical Information Systems (IAIMS): payoffs and problems. AB - IAIMS (Integrated Advanced Information Management Systems) is an initiative to improve the access to information needed to provide patient care, health-oriented education, biomedical research, and management of large medical center environments. This paper will review the goals, history, and accomplishments of the IAIMS initiative. Shortcomings and frustrations, lessons learned, and the future of such initiatives will also be discussed. PMID- 7799813 TI - Safety and decision support in oncology. AB - The management of patients with cancer involves the administration of complex treatment protocols with frequent monitoring of the effects of treatment on the malignant disease as well as on the general health of the patient. The number and wide variety of protocols used in treatment trials, and the amount of clinical data generated suggest the need for computer-based support. The toxicity of many of the treatments used and the severity of the disease itself underline the safety-critical nature of all decisions made by oncologists, the physicians and surgeons who treat cancer patients. This paper presents recent work on the analysis of safety issues arising from the design and implementation of a prototype decision-support system for oncologists. It illustrates the benefits of combining both informal and formal approaches to the analysis and representation of safety, firmly based on a thorough and detailed study of the domain in cooperation with oncologists, pharmacists and medical informaticians. PMID- 7799814 TI - Representation of medical concepts of the thyroid gland by physicians in anatomy and pathology. AB - An experimental study in cognitive psychology is described, concerning the categorization of medical concepts into specific classes, expressed by physicians specialized in anatomic pathology consultations of the thyroid gland. This study belongs to a medical computer science project, called ARISTOTLE, concerning Natural Language Processing of specialized medical reports in anatomic pathology of the thyroid gland. This research has been done for two reasons; first, to specify the characteristics of human expert categorization in an area of medical knowledge and, secondly, to validate the hierarchical organization of a prototype declarative knowledge base. In this experiment, physicians were asked to categorize 121 concepts into 10 proposed classes. These classes and concepts belong to expert knowledge represented in a conceptual graph that was constructed before the experiment. Results show variable semantic distances between concepts of a same class, and dynamic variations of these distances due to contextual representation. PMID- 7799812 TI - A temporal query system for protocol-directed decision support. AB - Chronus is a query system that supports temporal extensions to the Structured Query Language (SQL) for relational databases. Although the relational data model can store time-stamped data and can permit simple temporal-comparison operations, it does not provide either a closed or a sufficient algebra for manipulating temporal data. In this paper, we outline an algebra that maintains a consistent relational representation of temporal data and that allows the type of temporal queries needed for protocol-directed decision support. We also discuss how Chronus can translate between our temporal algebra and the relational algebra used for SQL queries. We have applied our system to the task of screening patients for clinical trials. Our results demonstrate that Chronous can express sufficiently all required temporal queries, and that the search time of such queries is similar to that of standard SQL. PMID- 7799815 TI - Human performance evaluation of a metaphor graphic display for respiratory data. AB - Metaphor graphics are data displays designed to look like corresponding variables in the real world, but in a non-literal sense of "look like". Evaluation of the impact of these graphics on human problem solving has twice been carried out, but with conflicting results. The present experiment attempted to clarify the discrepancies between these findings by using a complex task in which expert subjects interpreted respiratory data. The metaphor graphic display led to interpretations twice as fast as a tabular (flowsheet) format, suggesting that conflict between earlier studies is due either to differences in training or to differences in goodness of metaphor. Findings to date indicate that metaphor graphics work with complex as well as simple data sets, pattern detection as well as single number reporting tasks, and with expert as well as novice subjects. PMID- 7799816 TI - Evaluation of a decision-support system for inoperable non-small cell lung cancer. AB - The purpose of this study was to find out whether a decision-support system is able to assist a clinician in predicting patient outcome and in selecting optimal treatment in oncology. The domain of the evaluated decision-support prototype was primary therapeutic decision making in inoperable non-small cell lung cancer. The performance of the prototype was tested on retrospective material consisting of 112 patients treated by radiotherapy. Survival was the endpoint for examining whether the treatment decision proposed by the system was more accurate than the decision actually made by the clinician. Certain prognostic variables were used by the system to classify patients into two treatment groups, radical or palliative radiotherapy. The median survival times of these groups were 15 and 7 months, respectively, compared with 9 and 8 months in the corresponding groups classified by the clinician. Our results indicate that clinicians need support in treatment selection and that decision-support systems could be a potential answer. PMID- 7799817 TI - The relative accuracy of a variety of medical diagnostic programs. AB - Acute abdominal pain is one of the most widely studied applications of computer aided diagnosis. The usual approach is to apply Bayes' theorem with the assumption of conditional independence ("independence Bayes"). We compared various approaches to designing diagnostic programs for abdominal pain of suspected gynaecological origin. The methods range from statistical to knowledge based. All programs were evaluated using a database of 1,270 cases collected retrospectively. Our results suggest that in this application no significant improvement in accuracy can be made by taking interactions into account, either by statistical or by knowledge-based means; independence Bayes is near-optimal. As far as accuracy is concerned, there appears to be little point in pursuing knowledge-based approaches. However, the "nearest neighbours" method using a new metric appears to be at least as accurate as independence Bayes. We argue that the nearest neighbours method is more suitable than independence Bayes for clinical use because of greater accountability. PMID- 7799818 TI - An integrated knowledge-based system to guide the physician during structured reporting. AB - A routinely used system for report generation, based on direct physician data entry, has been combined with a knowledge-based module. The knowledge-based system is operating in the background, and guides the user by dynamically suggesting diagnoses and generating hints regarding the actual and possible further diagnostic procedures. Hybrid technology with neural networks and rules is used. A laboratory evaluation has shown good agreement between diagnoses suggested by the system and confirmed diagnoses, with a kappa coefficient of 0.85 and an area under the ROC curve of 0.92. In a survey following a 14-day test period, physicians stated that the system was both sensible and helpful. The current application domain is ultrasound reporting. PMID- 7799819 TI - A physician-based architecture for the construction and use of statistical models. AB - Physicians need specially tailored computer tools to take advantage of published research results. We present a knowledge-based computer framework--the physician based (PB) architecture--for constructing such tools, and we use the problem of physicians' interpretation of two-arm parallel randomized clinical trials (TAPRCT) as a working example. Statistical models are represented by influence diagrams. The interpretation of influence-diagram elements are mapped into users' language in a domain-specific, physician-based user interface, called a patient flow diagram. Statistical-model transformations that maintain the semantic relationships of the model and that embody clinical-epidemiological knowledge are encoded in a mediating structure called the cohort-state diagram. The algorithm that coordinates the interactions among the knowledge representations uses modular actions called construction steps. This architecture has been implemented in a Bayesian system, called THOMAS, that supports physician decision making in light of TAPRCT data. This support entails assessing clinical significance, prior beliefs, and methodological concerns. We suggest that the PB architecture applies to a wide range of statistical tools and users. PMID- 7799820 TI - An intelligent Computer-Assisted Instruction system for clinical case teaching. AB - The use of computers in the field of medical education is common. Our purpose is to present a Computer-Assisted Instruction system which has been developed over ten years at the University of Compiegne and the University of Rennes Medical School. This system can be used to help the student to solve clinical cases by analyzing and critiquing their answers and by using a knowledge base which has been previously structured in a rule network. It is an intelligent Computer Assisted Instruction system comprising an author module, a pedagogical module and a student module. The CAI system can be used as a simulation model for any type of diagnostic or therapeutic problem. In this paper we present the author and pedagogical module which have been built using our previous work on intelligent computer-assisted instruction systems. PMID- 7799821 TI - The climacteric cross-culturally: the International Health Foundation South-east Asia study. PMID- 7799822 TI - Climacteric and menopause in seven South-east Asian countries. AB - The menopause is universal, but what about the climacteric? In an attempt to answer this question, a study was conducted in seven south-east Asian countries, namely, Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore and Taiwan. Samples of approximately 400 women in each country were questioned about a number of climacteric complaints, incontinence and dyspareunia, consultation of a physician, menopausal status and several background characteristics. Special care was taken to overcome linguistic and cultural problems, and the data collected were kept as objective as possible. From the results obtained we were able to show that the climacteric was indeed experienced in south-east Asian countries, although in a mild form. The prevalence of hot flushes and of sweating was lower than in western countries, but was nevertheless not negligible. The percentages of women who reported the more psychological types of complaint were similar to those in western countries. The occurrence of climacteric complaints affected perceived health status. A physician was consulted for climacteric complaints by 20% of the respondents, although this was most frequently associated with the occurrence of psychological complaints and less so with that of hot flushes and sweating. The median age at menopause (51.09) appeared to be within the ranges observed in western countries. Ethnic background and age at menarche were found to have a significant influence on age at menopause. The study clearly demonstrated that climacteric complaints occur in south-east Asia. The findings suggest, however, that vasomotor-complaint-related distress might be 'translated' into psychological complaints, which are more frequently considered to warrant consulting a physician. PMID- 7799823 TI - The climacteric of Chinese factory workers. AB - Chinese factory workers (427) mainly of Fujian origin were found to have few climacteric symptoms. Of these, 65% and 50% reported having no circulatory and nervosity symptoms, respectively. Only 18% of women experienced hot flushes. The climacteric symptoms were more pronounced at the perimenopausal period (P < 0.001) when these women experienced more irregular menstruation. Low socio economic status and educational level did not have adverse effects on the symptom reporting. High parity and employment may be positive factors in this period of change of life. A majority of women (74%) felt that the climacteric and menopause is a natural process which caused them no concern. Of those who were still menstruating 80% did not anticipate that they would have problems with the climacteric and menopause. These women's different climacteric pattern could be related to their introspective abilities to cope adequately or in an impersonal manner. PMID- 7799824 TI - Climacteric Filipino women: a preliminary survey in the Philippines. AB - In a survey of 500 Filipino women aged 40-50 years, of various professions and residing mostly in Metropolitan Manila, the average age of menopause was estimated at 48 years. The climacteric symptoms were seen to affect 83% of the respondents. Sixty-three percent reported menopause-related circulatory or vasomotor disorders and 79% mentioned psychological disorders. The incidence and frequency of climacteric symptoms were highest among the perimenopausals. Headache was the most common climacteric symptom, while the hot flush was the least prevalent. Only 31% consulted a physician for menopause-related ailments. Eighty-six percent of those who consulted were prescribed medication, however, only 52% of these followed the prescription. Eleven percent reported dyspareunia and only 36% consulted a doctor. Thirty-one percent suffered from urinary stress incontinence and only 16% consulted a doctor. The findings of this study suggest that the average Filipino woman has an attitude of forbearance towards the climacteric syndrome. This attitude is shaped by her Asian culture and Third World circumstances. PMID- 7799825 TI - Health of Indonesian women city-dwellers of perimenopausal age. AB - In the last few years more women of climacteric age, living in urban areas, have been seeking medical care. In 1989, on the invitation of 6 women's organizations in Jakarta and other cities, the Indonesian Menopause Society gave talks and held discussions in cooperation with the Department of Obstetrics and Gynaecology, Faculty of Medicine of the University of Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta. These occasions were used to accumulate data from women participants of 40 years of age and older. The age of the respondents ranged between 40-59 years. Most were 42 years old (13.9%). Ninety-four percent were still married. Twenty-five percent had three living children. Sixty-three percent of the respondents were high school graduates who worked full time (33%), part time, or were unemployed. The average menarche age was 13 and menopausal age 50 51. Menopausal complaints were rare, hence medical consultations were rare. Tranquilizers were prescribed for those who did seek medical help. This data constitutes the basis of the formulation of a strategy to solve menopause related problems in Indonesia, where female life expectancy, and the contribution of women to society, is on the increase. PMID- 7799826 TI - The prevalence of symptoms in menopausal women in the Far East: Singapore segment. AB - Questionnaires (4000) on experience of menopausal symptoms in Singaporean women aged 40-55 were distributed by students. In total, 524 envelopes were returned (13.1%) and of these 420 were analyzed. Of these, 366 were classified as either pre-, peri- or postmenopausal on the basis of their menstrual patterns. Menopausal symptoms in this sample of Singaporean women were, in general, similar to those experienced in the West though the prevalence was low compared to European studies. No significant differences in individual symptoms were found between the 3 groups but, taken together, symptoms were significantly highest in the perimenopausal and lowest in the other menopausal groups. In the postmenopausal group 50% had been menopausal for at least 1 year at 50.5 years. PMID- 7799827 TI - A study on the menopause in Malaysia. AB - In an attempt to gather data on the menopause in Malaysia, 400 women (13% Chinese, 70% Malays and 16% Indians), representing the three major ethnic groups in Malaysia, were interviewed. The majority (76%) of these women were still married and living with their husbands and 63% of them were working. Most of them (90%) had attained menarche by the age of 15 years and 50% of them had married before the age of 20. Their reproductive record was good, since 76% of them had 3 or more children who were still alive. The mean age at menopause in the Malaysian women studied was 50.7 years. Analysis of the climacteric symptoms reported showed significant differences in the vasomotor and nervosity indices in the perimenopausal and postmenopausal groups. Eighty percent (80%) of the women saw no need to consult a doctor about their climacteric symptoms. When they did, most of them (84%) received medication, but 43% of them did not comply with the prescribed treatment. Dyspareunia and urinary incontinence were evidently regarded as embarrassing complaints in all three groups, since around 80% of the women did not seek medical advice. This is not surprising in view of the fact that 89% of them rated their health as good. PMID- 7799828 TI - Effect of a conjugated oestrogen (Premarin) cream on ageing facial skin. A comparative study with a placebo cream. AB - The effects of Premarin cream on ageing facial skin were studied in a randomised, double-blind, parallel group study. Fifty-four women aged 52-70 years who had moderate to severe facial cutaneous ageing, applied 1 g of either Premarin cream (0.625 mg conjugated oestrogens per gram of cream), or placebo cream (same composition with the exclusion of conjugated oestrogens) to the face nightly for 24 weeks. Each morning these women protected their face with a sunblock SPF 15. Skin thickness was measured by B-scan ultrasonic echography, and skin microrelief by profilometry. Each subject's facial appearance was also evaluated by the subject herself and by the clinician. A statistically significant difference (P = 0.013) in favour of Premarin cream was detected in skin thickness at week 24. Skin thickness (dermal plus epidermal) for the women who used Premarin cream increased from 1.56 +/- 0.20 mm at baseline to 1.68 +/- 0.19 mm, compared with 1.52 +/- 0.20 mm at baseline to 1.59 +/- 0.19 mm in the placebo group. Premarin cream was also significantly more effective than placebo cream in improving fine wrinkles according to the results at weeks 12 and 24 (P = 0.010 and P = 0.012, respectively). Significant improvement from baseline was detected in both groups for roughness, laxity and mottled pigmentation and/or lentigines; however, there was no significant difference in these parameters between the two treatment groups. No subjects discontinued treatment for a safety reason. In conclusion, Premarin cream produced better results than the placebo cream; the difference was statistically significant for skin thickness and fine wrinkles. Premarin cream was well tolerated locally, and its general safety was good. PMID- 7799829 TI - Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use. AB - Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17 beta-oestradiol with 1 mg norethisterone acetate [E2 + NETA]; 2 mg oestradiol valerate with 75 micrograms levonorgestrel [E2V + LNG]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E2V + MPA]; or 1.5 mg 17 beta-oestradiol with 150 micrograms desogestrel [E2 + DG]. A placebo controlled study lasting 12-24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3-6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E2V + LNG, 21% of the women women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness. PMID- 7799830 TI - Is Livial diabetogenic? PMID- 7799831 TI - Polymerase chain reaction analysis of Borrelia species isolated in Japan. AB - Primer reactivities of 25 Borrelia burgdorferi sensu lato isolates from the ticks, Ixodes persulcatus and I. ovatus, in Japan and 10 isolates in Europe and North America were investigated. The methods used in this study were the polymerase chain reaction (PCR) on the flagellin structural gene (fla), the outer surface protein A gene (osp A) and the outer surface protein B gene (osp B), and the restriction fragment length polymorphism (RFLP) analysis of PCR products from osp A and osp B. The flagellin PCR primer set reacted with all the Borrelia strains tested. Four genospecies, B. burgdorferi sensu stricto, B. garinii, B. afzelii and B. japonica, were differentiated by PCR using osp A and osp B primers combined with RFLP analysis. Some Japanese isolates from I. persulcatus were identified as B. garinii or B. afzelii. The other isolates from I. persulcatus did not fit in any of the 4 genospecies. These results suggested that Japanese isolates from I. persulcatus are highly heterogeneous in their osp A and osp B structures. Furthermore, PCR primers targeting fla are applicable to the gene diagnosis for Lyme disease in Japan, and osp A and osp B primers can be used to classify B. burgdorferi sensu lato isolates into genospecies by PCR and RFLP analyses. PMID- 7799832 TI - Comparison of the virulence of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. AB - The virulence of methicillin-resistant Staphylococcus aureus (MRSA) was compared with that of methicillin-sensitive S. aureus (MSSA), using 13 MRSA and 7 MSSA strains isolated from clinical specimens. The infectivity and lethality of the two groups were examined as to the inoculum required to infect 50% of guinea pigs (ID50) and to kill 50% of mice (LD50), respectively. The mean ID50 [log10 colony forming units (CFU)] for MRSA strains was 7.1 +/- 0.60 standard deviation, which was 1.5 higher than that for MSSA strains (P < 0.001). The mean LD50 (log10 CFU) for MRSA strains was 9.0 +/- 0.42, being 1.1 higher than that for MSSA strains (P = 0.001). Pretreatment of mice with cyclophosphamide decreased the mean LD50 for MRSA strains more than that for MSSA strains, resulting in the difference in the mean LD50 being insignificant (P = 0.502). These results indicate that MRSA is less virulent than MSSA in normal hosts, but that they are equally virulent in immunocompromised hosts. The growth of MRSA strains was much slower than that of MSSA strains in the lag phase, although their growth rates were almost the same in the exponential growth phase, suggesting that the difference in virulence between them may be at least partly due to such a difference in growth. PMID- 7799833 TI - The role of MRSA (methicillin-resistant Staphylococcus aureus) adherence and colonization in the upper respiratory tract of geriatric patients in nosocomial pulmonary infections. AB - The mechanism of nosocomial respiratory infections caused by MRSA (methicillin resistant Staphylococcus aureus) in geriatric patients was investigated. Seriously ill patients (SIP) undergoing naso-gastric tube feeding or intravenous hyperalimentation and moderately ill patients (MIP) who were orally fed, were examined for their colonization and infection by Staphylococcus aureus (S. aureus) in the respiratory tract. Colonization of MRSA in the upper respiratory tract in SIP was from six to ten times higher than that in MIP and was associated with a high incidence of MRSA pulmonary infections. In vitro S. aureus adherence to nasal or oropharyngeal cells demonstrated that bacteria binding to nasal cells was higher, which probably can be interpreted as an elevated occurrence of S. aureus colonization in the nasal cavity than in the throat. The binding activity of MRSA was not superior to that of MSSA (methicillin-sensitive S. aureus). Though MRSA binding to the nasal cells from SIP was not higher than those from MIP, MRSA colonization in the upper respiratory tract was more frequently seen in SIP (P < 0.01). A higher incidence of total infectious episodes (P < 0.02-0.001) and more frequent use of antibiotics (P < 0.02-0.001), which were potent against MSSA might be the basis for selection of MRSA in these patients. In fact, the rate of MRSA colonization on the skin (pressure sores) was also higher in SIP (P < 0.01). A low nutritional state in SIP (P < 0.01-0.02) might also be associated with MRSA colonization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799834 TI - A sandwich cup method for the penetration assay of antimicrobial agents through Pseudomonas exopolysaccharides. AB - We developed new sandwich cup method to assay the penetration of various antimicrobial agents through Pseudomonas exopolysaccharides. Using alginate extracted from mucoid-type Pseudomonas aeruginosa and gellan gum from Pseudomonas elodea, the role of exopolysaccharides as a barrier against drug penetration was examined. The penetration of positively charged hydrophilic drugs such as aminoglycosides and polypeptides was markedly inhibited by the gels tested, but that of beta-lactams, quinolones, and macrolides was not inhibited. The penetration of gentamicin was strongly influenced by the gel concentration, the solution to be used, and the presence of Ca2+. These results suggest that the microenvironment at the infection site could greatly influence drug penetration through biofilms in vivo. PMID- 7799835 TI - Infectivity and early antibody response to Borrelia burgdorferi sensu lato isolated in Japan in outbred mice. AB - Borrelia burgdorferi sensu lato isolated from Ixodes ovatus (B. japonica), I. persulcatus and patients with erythema migrans (EM) in Japan were determined on infectivity and arthritis induction-activity in outbred mice. Infectivity of B. japonica was weak and did not induce the development of footpad swelling by subcutaneous (s.c.) inoculation into the footpad. Challenged strain, NO129-M of B. japonica, to ddY mice were reinoculated to the mice at various cell numbers (1 x 10-1 x 10(6) cells/mouse). The strain isolated from the mouse did not reinfect ddY mice and did not induce the production of specific antibody to the homologous strain. On the other hand, strains from I. persulcatus and patients with EM in Japan infected the mice and induced a serious inflammatory response in Borrelia inoculated footpad as well as strains belonging to the three genospecies, B. burgdorferi sensu stricto, B. garinii, and B. afzelii, related to Lyme disease, from North America and Europe. The mice were infected with 10 cells of strain HP1 isolated from I. persulcatus in Hokkaido and of strain 297 isolated from a patient in the U.S.A. by subcutaneous inoculation into the hind footpad, or by intradermal inoculation into the back. Antigens of ca. 20, 23-24 (Osp C), 29, 39, 41 (flagellin) and 45 kDa reacted with the pooled sera from mice inoculated with strains HP1 and 297, but Osp A and Osp B did not. PMID- 7799836 TI - Crystallization and analyses of crystals of various chemotypes of R-form lipopolysaccharides from Salmonella spp. AB - Various chemotypes (Re, Rd2, Rd1P-, Rd1, RcP-, Rc, Rb3, Rb2, Rb1, and Ra) of R form lipopolysaccharides (LPSs) of Salmonella spp. were crystallized by treatment with 70% ethanol containing 250 mM MgCl2, and crystals of the LPSs were observed electron microscopically and analyzed by electron diffraction and synchrotron X ray diffraction. All the LPSs tested formed three-dimensional crystals showing very similar shapes; hexagonal plate, solid column, discoid, square or rectangular plate, lozenge plate and truncated hexangular or rectangular pyramid forms. Electron diffraction patterns from the hexagonal plate crystals of all these LPSs obtained by electron irradiation from the direction perpendicular to the basal plane showed that they consist of hexagonal lattices with the lattice constant of 4.62 A. The crystals of all the LPSs thus formed gave ring-like X-ray diffraction patterns because of their small sizes. The long-axis values were calculated from the X-ray diffraction patterns from crystals of all the LPSs in the low-angle region and they corresponded roughly to the length of the proposed primary chemical structures of the R cores of the LPSs. The volume occupied by a single molecule of all the LPSs were calculated from the molecular weights based on the proposed structures and the crystallographic data obtained by electron diffraction, X-ray diffraction, and density determination. PMID- 7799837 TI - Possible mechanism of action of beta-lactam-enhancing factor on methicillin resistant Staphylococcus aureus. AB - We have recently found a factor (Factor T) in aged mixtures of tungstate and phosphate which greatly enhances the antibacterial effects of beta-lactams on methicillin-resistant strains of staphylococcal species such as methicillin resistant Staphylococcus aureus (MRSA), but shows only weak effects on methicillin-susceptible S. aureus and bacterial strains other than staphylococci. Factor T alone did not strongly inhibit cell metabolism and bacterial growth unless an excess amount was added. When Factor T was added to the culture medium beforehand, the growth of MRSA cells was rapidly suppressed just after addition of oxacillin (MPIPC). However, the growth of the cells was inhibited gradually when these two reagents were added in reverse order. For full expression of the enhancing effect, it seemed necessary for cells of MRSA strains to be incubated with Factor T for at least 2-3 hr. When the cells were washed after being sensitized by incubating them for 5 hr with Factor T, it took approximately 1 hr for the cells to recover their resistance to MPIPC. Factor T reduced the amount of penicillin-binding protein-2' (PBP 2'), and thus sensitized the MRSA strains to beta-lactams. PMID- 7799838 TI - Detection of human immunodeficiency virus-1 nucleic acid on inactivated filter paper disks by polymerase chain reaction and microtiter plate assay. AB - Human immunodeficiency virus type 1 (HIV-1) in cultured cells, peripheral blood samples and sera were adsorbed on filter paper disks and inactivated by heat or ethanol. Two procedures, the polymerase chain reaction (PCR) and microtiter plate assay (HMPA) were used to detect the nucleic acid. The sensitivity after different heat treatments with nested PCR for HIV-1 DNA (or nested reverse transcription-PCR for HIV-1 RNA) was identical regardless of whether the samples were examined immediately or one month later. Inactivation by ethanol treatment resulted in a slight loss of sensitivity. The HMPA proved to be as reliable and specific as the conventional PCR technique. We conclude that the heat-treated filter paper disk assay is suitable for identifying HIV nucleic acid in clinical samples sent to the laboratory from a distance, e.g. in an envelope. PMID- 7799839 TI - Binding of host-associated treponeme proteins to collagens and laminin: a possible mechanism of spirochetal adherence to host tissues. AB - The polypeptides of seven strains of human treponemes were investigated by immunoblot analysis for their binding to the human placental collagens and laminin. Of the treponemal polypeptides, eleven polypeptides, 45-kDa, 49-kDa, and 62-kDa polypeptides from T. pallidum ATCC 27087, a 48-kDa polypeptide from T. phagedenis biotype Reiter, 51-kDa and 53-kDa polypeptides from T. vincentii ATCC 35580, 30-kDa, 53-kDa and 63-kDa polypeptides from T. socranskii subsp. buccale ATCC 35534, a 52-kDa polypeptide from T. denticola ATCC 35405, and a 53-kDa polypeptide from T. denticola ATCC 33520 possessed an ability to bind to the laminin, type I, III, IV, or V collagen. An intermediate-sized human oral isolate strain G7201 did not possess any laminin- or collagen-binding polypeptides. Immunoelectron microscopy using intact treponemal cells with a single collagen binding polypeptide and the corresponding antisera demonstrated that the 51-kDa and 53-kDa polypeptides from T. vincentii, the 53-kDa polypeptide from T. socranskii subsp. buccale ATCC 35534 and the 52-kDa polypeptide from T. denticola ATCC 35405, were outer envelope proteins. PMID- 7799840 TI - Detection of DNA of causative agent of spotted fever group rickettsiosis in Japan from the patient's blood sample by polymerase chain reaction. AB - The polymerase chain reaction (PCR) was applied for the etiological diagnosis of spotted fever group (SFG) rickettsiosis in Japan. Nucleotide primers derived from the 17-kDa antigen gene of Rickettsia rickettsii primed a rickettsia-specific 246 base-pair product for all of the Katayama, Abe, Misaka and Kojima strains, which we had isolated previously. Moreover, we were able to detect the same product by PCR amplification from the peripheral blood of a patient in the acute stage of the illness. The PCR method is considered to be useful for rapid etiological diagnosis of SFG rickettsiosis in Japan. PMID- 7799841 TI - Localization of apoptosis (programmed cell death) in mice by administration of lipopolysaccharide. AB - Localization of apoptotic cells by administration of lipopolysaccharide into mice was studied by using the in situ specific labeling of fragmented DNA. This method clearly stained the nuclei of thymocytes at the cortex of the thymus. The nuclei of cells in the bone marrow and in the spleen were also positively stained. It was suggested that the cortex in the thymus is where the LPS-induced programmed cell death occurs. PMID- 7799842 TI - Detection and typing of human rotavirus in reference to repeated acute gastroenteritis in infants. AB - Stool specimens from infants who visited a clinic because of acute gastroenteritis were tested for the presence of human rotavirus. Among the samples obtained were specimens taken from seven patients who had visited the clinic at two different times. In six of these seven children, human rotavirus (HRV) was detected in only one of the specimens taken (i.e. during only one of the two visits). One patient was shown to have excreted HRV twice; in both cases the HRV was serotyped to be type 1. The present results indicate that the symptomatic reinfection of HRV was not a widely occurring phenomenon in the group of infants tested. PMID- 7799843 TI - A similar expression pattern of adhesion molecules between intermediate TCR cells in the liver and intraepithelial lymphocytes in the intestine. AB - Two major populations of extrathymically differentiated T cells exist in the liver and intestine. Such T cells in the liver have TCR of intermediate intensity (i.e., intermediate TCR cells) and constitutively express IL-2 receptor beta chain (IL-2R beta), whereas those in the intestine, especially intraepithelial lymphocytes, have TCR of bright intensity, consisting of a mixture of IL-2R beta+ and IL-2R beta-. All mature thymocytes and thymus-derived T cells seen in the peripheral immune organs are TCR-bright+ IL-2R beta- under resting conditions. When the expression pattern of adhesion molecules, including CD44, L-selectin, LFA-1 and ICAM-1, was compared among these T-cell populations, they displayed quite unique patterns of expression. All extrathymic T cells in the liver, intestine, and even other organs were CD44+ L-selectin-LFA-1++ICAM-1+, whereas thymocytes and thymus-derived T cells were CD44-L-selectin+LFA-1+ICAM-1-. This inverted expression of adhesion molecules between extrathymic T cells and thymus derived T cells might be associated with their unique tissue-localization. PMID- 7799844 TI - Drugs for asthma. PMID- 7799845 TI - [The fauna and ecology of blackflies (Diptera, Simuliidae) in the Republic of Guinea]. AB - Twenty-nine Simulium species were recorded in the Republic of Guinea. The geographical distribution of the blackfly species in its areas is shown in the paper. The most probable vector of Onchocerca volvulus are S. damnosum s. str and S. sirbanum which predominate in the landscapes of Sudan and Guinea savannas. S. yahense, S. soubrense, and S. sanctipauli are likely to be vectors in the forest savannas and tropical rain forests. PMID- 7799846 TI - [The insecticidal activity of thermal aerosols of permethrin]. AB - The aerosols derived from the designed 2% permethrine-containing pyrotechnical formulations (tablets and briquets) were tested for their effects in laboratory and field conditions. When tested in the chamber, its LC50 and LC99 were 0.056 and 0.43 mg/m2 (as calculated for the active ingredient), respectively, for Ae. aegypti mosquitos exposed to 15 min in the polycarprolactam plastic trap and 2.99 and 5.66 mg/m2 (for the active ingredient) for M. domestica flies exposed to an hour. LC99 for C. pipiens ranged 2 to 5 mg/m2 in the field conditions when treating the basements with varying airtightness. The effective dosage ensuring a 100% death of M. domestica in the animal-breeding premises of various types is 10 mg/m2 on an hour exposure. PMID- 7799848 TI - [The effect of hydraulic engineering construction in the Volga basin on the situation with opisthorchiasis and diphyllobothriasis. 2. The prognosis for a change in the parasitological situation in the area of small reservoirs]. PMID- 7799847 TI - [The rate of infection of the taiga tick with Borrelia in the western Sayan]. AB - The paper provides microscopic findings of taiga ticks collected for the causative agent of Lyme's disease in May to July 1993 in the West Sayan . A total of 1,016 specimens were examined, among them 124 (12.2%) were found to have Borreliae. The areas were demonstrated to vary greatly with their epidemiological risk. The number of ticks and hence the epidemiological risk were the most in the low-mountain and chern taiga areas. PMID- 7799850 TI - [The procedure for the wide use of praziquantel in a complex of measures to control opisthorchiasis. 1. The tolerance and efficacy of different doses of biltricide during outpatient use in foci]. AB - The results of wide uses of praziquantel (bilthricide, Bayer, Merck) to treat 2,440 persons in the outpatient setting of the endemic foci of opisthorchiasis in Tomsk Province suggest that the agent is highly effective (on the average of 97%) and well tolerable. There are no great differences in the efficiency of treatment, the frequency and magnitude of adverse reactions during out- and inpatient treatments. There are no either basic differences in the efficacy of praziquantel doses of 30, 40, and 60 mg used in the treatment of patients with Opisthorchis infection in whom 1 to 1.00 eggs per g feces are found. The use of praziquantel in a daily dose of 30 or 40 mg/kg in the outpatient setting permits the mass drug therapy of the population in the endemic foci, by reducing expenses on treatment. It is advisable to continue investigations of praziquantel used in small doses among the populations at low infection risk. PMID- 7799849 TI - [The action of insect developmental regulators on the housedust mites Dermatophagoides pteronyssinus (Trouessart, 1897) and D. farinae Hughes, 1961 (Acari: Pyroglyphidae)]. AB - Whether insect growth regulators, such as methoprene, telflubenzuron and flufenoxuron, can be used to suppress the populations of the house dust mites D. pteronyssinus and D. farinae has been studied in the laboratory setting. The most potent agent has been found to be methoprene used in concentrations of 0.05 = 0.1%, in particular. Flufenoxuron at a concentration of < 0.1% has been shown to stimulate the reproduction of house dust mites. PMID- 7799852 TI - [The epizootiological problems of trematodiases in the Maritime Territory]. AB - Five species of trematodes: Metagonimus yokogawai, M. katsuradai, Centrocestus armatus, Nanophyetus salmincola schikhobalowi and Paragonimus westermani ichunensis which are able to infect man have been found to develop with the participation of mollusks of the Juga genus from the rivers of the Maritime Territory. Some epizootiological aspects of the infections caused by these trematodes are considered in the paper. PMID- 7799851 TI - [Cases of trichinelliasis among the inhabitants of Lipetsk Province]. PMID- 7799853 TI - [The distinctive epidemiology of parasitic diseases]. PMID- 7799855 TI - [The pathomorphological changes in the kidneys of white mice with experimental trichocephaliasis and after the use of anthelmintic preparations]. AB - The experiments were carried out with 170 white mice divided into 4 groups. The first group consisted on 72 intact animals, administered subcutaneous ivomek (0.01 ml/kg) and oxfendasole (10 mg/kg) per os; Group 2 consisted of 15 animals with induced trichocephaliasis, administered no anthelmintics. The third group, 72 animals, were infected with Trichocephalus muris invasion eggs and administered anthelminthic agents on day 46 postinfection. The fourth group consisted of 11 intact animals, neither infected, nor treated (reference group). The animals were decapitated 3, 12, 24 and 72 h after the drug administration and histologic examination of the kidneys was carried out. The findings evidence that the morphologic changes in the kidneys of mice with trichocephaliasis are characterized by alternating proliferative processes. Both the drugs used were found characterized by a more or less pronounced nephrotoxicity. Ivomek induced the most marked structural changes in the kidneys of intact animals. The changes in the kidneys of intact mice were more manifest after the drugs administration than in intact animals. PMID- 7799854 TI - [The effect of emotional stress on the efficacy of chemotherapy in experimental trichochephaliasis]. AB - In DBA/2st mice experimentally infected with Trichocephalus muris the emotional stress caused by a cat that was placed for 2 hours twice a day during 14 days or more was found to reduce the efficiency of specific drug therapy with albendasole. At the same time there was an increase in the ED84:ED16 ratio (the effective dose of the drug which allows 84 or 16% of helminths to be eliminated), which decreased elimination probability in the whole helminth populations. PMID- 7799856 TI - [The attack activity of Uranotaenia unguiculata Edwards, 1913 mosquitoes on man]. AB - Field observations of the activity of U. unguiculata mosquitoes, carried out in the daytime, and 225-min estimations of their numbers against a white screen, lighted with an electric lamp, with half-an-hour intervals between the estimations, that were carried out in the evening and night hours in June, 1988, in the Divichinskii District of Azerbaijan, have demonstrated the aggressiveness of these mosquitoes towards humans. Daily changes in the activity of these mosquitoes were revealed, that consisted of an evening (high) and morning (poorly manifest) maximums and the high and daytime minimums. U. unguiculata bites were not so painful and the skin reactions poorly manifest in comparison with those of other mosquito species, which fact explains, in the authors' opinion, the inadequate interest of scientists to these mosquitoes. PMID- 7799857 TI - [The search for new antiparasitic agents. 12. The synthesis and study of the anti Echinococcus and anti-Hymenolepis activity of 6-[4-(4-alkylpiperazinyl-1) phenylamino]-1,2,5-thiadazolo[3 ,4-h] quinolines]. AB - The paper describes the synthesis of 6-[4-alkylpiperazinyl-1)phenylamino]-1,2,5 thiadiazolo[3,4-h ]quinolines where methyl (Drug G-1574) and ethyl (Drug G-1569) are alkyls. The two agents are as effective as mebendazole against the larval stage of Echinococcus multilocularis infection. Drug G-1574 has been demonstrated to ensure 100% recovery of spontaneously Hymenolepis nana-infected albino mice given doses 2.5-5 times lower than the effective dose of phenasal (niclosamide). PMID- 7799859 TI - [The comparative efficacy of commercial tests (of Russian and Swiss manufacture) for immunoenzyme analysis in echinococcosis]. PMID- 7799862 TI - [Parasitological objects in myths and ancient cultural monuments (a lecture)]. PMID- 7799860 TI - [Helminthiases in the Republic of Bashkortostan]. PMID- 7799858 TI - [The ecological-epidemiological characteristics of opisthorchiasis in Sverdlovsk Province]. AB - Opisthorchiasis has been recorded as the prevalent invasion in the adults over many years in the Sverdlovsk Region. The 1986-1991 studies have shown that there are Opisthorchis infection foci, by infecting 10.0-30.0% of the population, 12.0 73.0 of the Cyprinidae fish, and 0.2% of the Codiella mollusks in Sverdlovsk Province that is central in the middle Urals economic area. The irregular anthropogenic loading, such as the number of water reservoirs, specific features of their constructions and operation, in the river basins of the Sverdlovsk Region varies, by affecting the living conditions, spread of intermediate hosts and circulation of the vector, by predetermining the heterogeneous functioning of Opisthorchis infection foci. Some display their development, the others exhibit their regression due to unfavourable conditions for the vector in the impact areas of hydrological constructions. The areas that are different in the endemicity of opisthorchiasis and the nature of vector transmission were identified and characterized. There were 4 area types in terms of the nature of opisthorchiasis vector transmission. PMID- 7799861 TI - [The prevalence of enterobiasis among the boarding-school pupils in the city of Ufa]. PMID- 7799864 TI - Analytic modeling of photon scatter from flattening filters in photon therapy beams. AB - Analytic models for calculation of scatter distributions from flattening filters in therapy photon beams are presented. It is shown that the amount of scatter with high atomic number filters can vary from 2% in 4-MV beams to 10% for 24-MV beams. The use of low atomic number filters can increase the amount of scatter by a factor of 2. The dependence on the opening angle of the primary collimator is quite large since a larger opening angle requires a thicker filter, which increases the scattered fraction of the filtered beam. The scatter makes the filter act as an extended source of extra-focal radiation. The source distribution for monomedia filters is shown to be almost triangular. Integration in the calculation-point's eye view over the visible part of the filter scatter source yields the scatter fraction of the total energy fluence incident upon the patient. The experimentally well-known "tilt" of dose profiles for asymmetrical fields is explained by the model. For complete modeling of head scatter distributions in treatment planning, the model presented must be combined with models also describing the scatter from the collimators, auxiliary modulators such as wedges and compensating filters, and collimator backscatter to the beam monitor. PMID- 7799863 TI - [A method for stratifying malariogenic territories in order to construct a system of mathematical models of the prevalence of malaria. 1]. AB - The paper describes procedures for stratifying malariogenic areas that are homogeneous in the development pattern for epidemic stratum rises, which will be used to design a set of mathematical malaria spread models. The first stage of the procedures is to stratify P. falciparum and P. vivax malaria on phase planes. The morbidity rate of P. falciparum and P. vivax malaria was analyzed in the north-western areas of India in 1975-1990. Eighty-two observations provided 4 types of phase curves for tropic malaria, which form a polygon, a loop polygon, U shaped ones and those without any specific signs and 4 groups of phase curves for P. vivax malaria and the U-shaped phase curve with a loop for P. vivax malaria. It is shown that there is a steady-state pattern of phase curve changes in 71%. It is suggested that the pattern of a phase curve can be a diagnostic characterization of the given area. PMID- 7799865 TI - Dose calculation for photon beams with intensity modulation generated by dynamic jaw or multileaf collimations. AB - A dose calculation algorithm has been developed for photon beams with intensity modulation generated by dynamic jaw or multileaf collimations. First, an in-air fluence distribution is constructed based on the dynamic motion of the jaws or leaves, taking into account the variation of output with field size defined by the jaws. The fluence distribution is then convolved with the appropriate pencil beam kernel to give correction factors which are used to calculate the dose distribution for an intensity-modulated photon field. The proposed algorithm is strictly valid in homogeneous media only, patient heterogeneity correction is accounted for in an approximate manner. Dose distributions at several depths and for several field sizes were calculated for 6- and 15-MV x-ray beams for a set of standard wedges produced by dynamic jaws. Measurements were made with film and an ion chamber. Comparisons between calculated and measured data show good agreement (within 2%) for both dose profiles and wedge factors. Similar calculations and measurements were also made for a 25-MV intensity-modulated photon field produced by dynamic motion of a multileaf collimator. Agreement between calculations and measurements is also good (within 3%). The "tongue-and-groove" effect associated with a multileaf collimator design is also examined using a ring-shaped field produced by matching two component fields. The computation time for a dynamic collimated field is the same as that for an irregular field shaped by conventional blocks. The algorithm is applicable to any pattern of jaw or multileaf motions. The strengths and remaining problems of the algorithm are discussed. PMID- 7799866 TI - Dosimetry of centrally shielded electron beams. AB - In electron beams, the dose in phantom under the central shielding depends on electron-beam energy, depth in phantom, and shield area and thickness. In our experiments, all shield thicknesses were larger than the range of electrons in the shield material. At a given depth, the dose under the shield never exceeds the open field value; however, it can attain quite a large proportion of the open field value despite a shield thickness which exceeds the range of electrons in the shield material. The effects of shield area on the dose under the central shields were studied in detail and dose distributions are given as a function of shield lateral dimensions and electron-beam energy. It is shown that in clinical use of central shielding, the best approach to dose estimation under the shield is direct measurement in phantom under conditions of the actual clinical setup. PMID- 7799867 TI - The calibration and use of plane-parallel ionization chambers for dosimetry of electron beams: an extension of the 1983 AAPM protocol report of AAPM Radiation Therapy Committee Task Group No. 39. AB - This report is an extension of the 1983 AAPM protocol, popularly known as the TG 21 Protocol. It deals with the calibration of plane-parallel ionization chambers and their use in calibrating therapy electron beams. A hierarchy of methods is presented. The first is to calibrate the plane-parallel chamber in a high energy electron beam against a cylindrical chamber which has an Ncylgas value that has been obtained from a NIST traceable 60Co beam calibration. The second method, which is recommended for implementation by the ADCLs is an in-air calibration against a NIST-traceable calibrated cylindrical chamber in a Cobalt-60 beam to obtain a plane-parallel-chamber calibration factor in terms of exposure or air kerma. The third method places the two chambers in a phantom in a Cobalt-60 beam, and leads to an Nppgas value for the plane-parallel chamber. This report also gives Nppgas/NxAion)pp and Nppgas/(NkAion)pp values for five commonly used commercially available plane-parallel chambers: the Capintec PS-033, the Exradin P-11, the Holt, the NACP and the PTW-Markus. The calculation of these Ngas ratios introduces a Kcomp factor which is also calculated for the five parallel plate chambers. The use of the plane-parallel chambers follows the 1983 AAPM protocol for absorbed dose calibrations of electrons, except that new energy-dependent Prepl values are given for the Capintec PS-033 and PTW-Markus chambers consistent with the consensus of reports in the literature. For all the chambers, however, Prepl is unity for 20 MeV electrons. This report does not address the issue of the use of plane-parallel chambers in calibrating photon beams. PMID- 7799868 TI - Addendum to the penumbra of a 6-MV x-ray beam as measured by thermoluminescent dosimetry and evaluated using an inverse square root function [Med. Phys. 20, 1429-1438 (1993)]. PMID- 7799869 TI - Noise analysis in real-time portal imaging. I. Quantization noise. AB - The limit at which quantization noise becomes dominant in video-based real-time portal imaging has been studied. Quantization noise due to truncation in integer frame averaging is shown to be dominant over the input analog-to-digital converter (A/D) quantization noise, unless image addition is used in video-based real-time portal imaging systems. Portal images acquired with the Newvicon camera by averaging more than 64 frames are found to be dominated by the quantization noise due to truncation. It has shown that the signal-to-noise ratio (SNR) is limited to 886.8 when using an 8-bit A/D with digital frame averaging, but higher values can be achieved with digital frame addition. It is also shown that digital frame addition together with 16-bit processing can achieve higher contrast resolution than digital frame averaging and 8-bit processing. PMID- 7799870 TI - Thick phosphor screens for on-line portal imaging. AB - Gd2O2S phosphor screens between 250 and 1000 mg/cm2 thick were evaluated for use in megavoltage imaging systems. The phosphor layers were placed on brass plates ranging from 1 to 5 mm thick, each with and without an optical back reflector (white paint). Light output and spatial resolution were measured at 6- and 23-MV x-ray energies. Light output was found to increase linearly with phosphor thickness up to 500 mg/cm2, reaching a plateau at 1000 mg/cm2. Spatial resolution [modulation transfer function (MTF)] decreased exponentially with phosphor thickness up to 750 mg/cm2, where a minimum was reached. The variation of MTF with phosphor thickness was found to obey a simple empirical relation. PMID- 7799871 TI - Performance of glass fiber antiscatter devices at mammographic energies. AB - Using fiber optic manufacturing techniques, it is possible to produce a radiographic grid that discriminates against scattered radiation in two dimensions. Such grids consist of septa composed of glass with a high lead content; the interspace material is air, so that approximately 80% of the grid area is open. In this way, effective high ratio grids can be produced with relatively low Bucky factors. The performance of samples of such grid material is characterized in terms of both scatter rejection and dose efficiency for application in digital mammography in both slot-beam and area-beam geometry. For area beams, five- to tenfold improved scatter rejection relative to conventional grids was observed. In slot configurations, such grids could provide improved SNR/dose performance and more effective utilization of the heat loading capability of the x-ray source. PMID- 7799872 TI - Improving the convergence of iterative filtered backprojection algorithms. AB - Several authors have proposed variations of the iterative filtered backprojection (IFBP) reconstruction algorithms claiming fast initial convergence rates. We have found that these algorithms are trying to minimize an unusual squared-error criterion in a suboptimal way. As a result, existing IFBP algorithms are inefficient in the minimization of the criterion, and may become unstable at higher iteration numbers. We show that existing IFBP algorithms can be modified to use the steepest descent technique by simply optimizing the step size at each iteration. Further gains in convergence rates can be achieved with conjugate gradient IFBP algorithms derived from the same criterion. The steepest descent and conjugate gradient IFBP algorithms are guaranteed to converge, unlike some IFBP algorithms, and will do so in fewer iterations than existing IFBP algorithms. PMID- 7799873 TI - The measurement of radiation dose profiles for electron-beam computed tomography using film dosimetry. AB - The unique geometry of electron-beam CT (EBCT) scanners produces radiation dose profiles with widths which can be considerably different from the corresponding nominal scan width. Additionally, EBCT scanners produce both complex (multiple slice) and narrow (3 mm) radiation profiles. This work describes the measurement of the axial dose distribution from EBCT within a scattering phantom using film dosimetry methods, which offer increased convenience and spatial resolution compared to thermoluminescent dosimetry (TLD) techniques. Therapy localization film was cut into 8 x 220 mm strips and placed within specially constructed light tight holders for placement within the cavities of a CT Dose Index (CTDI) phantom. The film was calibrated using a conventional overhead x-ray tube with spectral characteristics matched to the EBCT scanner (130 kVp, 10 mm A1 HVL). The films were digitized at five samples per mm and calibrated dose profiles plotted as a function of z-axis position. Errors due to angle-of-incidence and beam hardening were estimated to be less than 5% and 10%, respectively. The integral exposure under film dose profiles agreed with ion-chamber measurements to within 15%. Exposures measured along the radiation profile differed from TLD measurements by an average of 5%. The film technique provided acceptable accuracy and convenience in comparison to conventional TLD methods, and allowed high spatial-resolution measurement of EBCT radiation dose profiles. PMID- 7799874 TI - Automated segmentation of regions of interest on hand radiographs. AB - Most radiologists do not use texture information contained in the trabecular patterns of hand radiographs to diagnose erosive changes and demineralization due to systemic inflammatory diseases that affect the skeletal system. However, high resolution digitization achievable by a laser digitizer now makes it possible to access texture information that may not be perceived visually. We are studying the feasibility of computer-assisted early detection of these processes with particular attention to patients with hyperparathyroidism. In this paper the methods used to extract a region of interest (ROI) for texture analysis are discussed. The techniques include multiresolution sensing, automatic adaptive thresholding, detection of orientation angle, and projection taken perpendicular to the line of least second moment. The methods were tested on a database of 50 pairs of hand radiographs. We segmented the middle and the index fingers with an average success rate of 83% per hand. For the segmented finger strips, we located ROIs on both the middle and the proximal phalanges correctly over 84% of the times. Texture information was collected in the form of a concurrence matrix within the ROI. This study is a prelude to evaluating the correlation between classification based on texture analysis and diagnosis made by experienced radiologists. PMID- 7799875 TI - Voxel-based localization in frame-based and frameless stereotaxy and its accuracy. AB - The problem of accurate stereotactic localization and registration of targets in computed tomography (CT) data sets is addressed, in particular the effect of using a single transformation matrix to map voxel coordinates onto stereotactic coordinates. An algebraic approach to the calculation of stereotactic target coordinates in tomographic data acquired with conventional stereotactic localizers is presented. The volume transformation matrix (VTM) is discussed, which is useful for the registration of volumetric data sets, and also corresponds to the rigid body transformation matrix used in many so-called frameless registration methods. The VTM can lead to accuracy degradation, in particular due to patient movement during scanning. Simulations were performed and CT data sets acquired with patients fitted with the CRW or the GTC stereotactic localizer were analyzed. Comparison of STM- and VTM-derived stereotactic coordinates shows an average overall registration error of 0.1 mm for anesthetized patients and in the range 0.6-1.4 mm for nonanesthetized patient. Accuracy maps are described that enable the user to visualize the registration error in relation to the data. It is shown that the effect of fiducial point localization error and patient movement for VTM-based localization is minimized when all available fiducials in the region of interest are used. The significance of these results is discussed, and methods are proposed to minimize these effects for frame-based and frameless registration methods. PMID- 7799876 TI - Photon propagation and detection in single-photon emission computed tomography- an analytical approach. AB - An analytical theory of photon propagation and detection in single-photon emission computed tomography (SPECT) for collimated detectors is developed from first principles. The total photon detection kernel is expressed as a sum of terms due to the primary and the Compton scattered photons. The primary as well as contributions due to every order of Compton scattering are calculated separately. The model accounts for the three-dimensional depth dependence of the collimator holes as well as for nonhomogeneous attenuation. No specific assumptions about the boundary or the homogeneity of the attenuating medium are made. The energy response of the detector is also modeled by the theory. Analytical expressions are obtained for various contributions to the photon detection kernel, and the multidimensional integrals involved are calculated using standard numerical integration methods. Theoretically calculated projections and scatter fractions for the primary and the first through second scattering orders are compared with our own experimental results for a small cylindrical primary radiation source immersed at various positions in a uniform cylindrical phantom. Also, theoretically calculated scatter fractions for a small spherical (pointlike) source in a uniform elliptic phantom are compared with experimental and Monte Carlo simulation results taken from the recent literature. The results from the analytical method are essentially exact and are free from the inaccuracies inherent in the numerical simulation methods used to deal with the photon propagation and detection problem in SPECT so far. The method developed here is unique in the sense that it provides accurate theoretical predictions of results averaged over an infinite number of simulations or experiments. We believe that our theory enhances an intuitive understanding of the complex image formation process in SPECT and is an important step toward solving the inverse problem, that of reconstructing the primary radiation source distribution from the measured gamma camera projections. PMID- 7799877 TI - Laser-induced thermoelastic deformation: a three-dimensional solution and its application to the ablation of biological tissue. AB - Under certain conditions, laser light incident on a target material can induce an explosive removal of some material, a process called laser ablation. The photomechanical model of laser ablation asserts that this process is initiated when the laser-induced stresses exceed the strength of the material in question. Although one-dimensional calculations have shown that short pulsed lasers can create significant transient tensile stresses in target materials, the stresses last for only a few nanoseconds and the spatial location of the peak stresses is not consistent with experimental observations of material failure in biological tissues. Using the theory of elasticity, analytical expressions have been derived for the thermoelastic stresses and deformations in an axially symmetric three dimensional solid body caused by the absorption of laser light. The full three dimensional solution includes three stresses, radial, circumferential and shear, which are necessarily absent in the simple one-dimensional solution. These stresses have long-lived components that exist for eight orders of magnitude longer in time than the acoustic transients, an important point when the details of dynamic fracture are considered. Many important qualitative features are revealed including the spatial location of the peak stresses, which is more consistent with experimental observations of failure. PMID- 7799878 TI - Two-dimensional registration of magnetic resonance brain images. AB - A fully automated two-dimensional image registration technique based on cross correlation is presented. This technique is evaluated using magnetic resonance images of human brain. Results indicate that this algorithm is capable of accurately estimating both linear and angular offsets. PMID- 7799879 TI - Comment on "radio frequency eddy current losses for an annular conductor in MRI: theory and applications" [Med. Phys. 20, 1555-1560 (1993)]. PMID- 7799880 TI - [Cystic fibrosis at present: current state and new perspectives]. PMID- 7799881 TI - The side-effects of non-steroidal anti-inflammatory drugs. PMID- 7799882 TI - [Progressive chronic external ophthalmoplegia. Personal experience]. AB - The author reports a case of mitochondrial myopathy which can be classified within the context of progressive chronic ophthalmoplegia and discusses the complex etiopathogenetic, histological and clinical aspects. In particular he underlines the severity of respiratory, muscular and bone symptoms and the important role played by histochemical and biochemical aspects in diagnosis. PMID- 7799883 TI - [Roseola infantum. Some epidemiologic, clinical and diagnostic aspects revisited. Personal experience]. AB - Seventy-five children aged less than 3 yrs, affected by Roseola infantum (maculopapular rash following an acute onset illness characterized by high fever for 2-5 days) were included in this study, 40% of them were admitted with urgency to our clinic for febrile convulsions. Several bacterial or viral agents other than HHV6 were isolated from more than 10% of the children; the role of HHV6 was studied with an immunofluorescence test (IFA) for specific antibodies (seroconversion); 25 single serum samples of the acute phase and 30 acute and convalescent paired sera were available; high positivity was shown in three preexanthematous samples; a serological evidence of HHV6 infection was obtained in only 9 of the 30 paired sera; a coinfection was shown in two subjects belonging to the last group; viral or bacterial agents other than HHV6, were demonstrated in 4 seronegative children. In our experience, the etiologic role of HHV6 in exanthema subitum is not always confirmed; we cannot explain the controversy of our results compared with those of Japanese literature. PMID- 7799884 TI - [Body mass index, weight and height in school children in central Italy]. AB - AIM: To study the pattern of distribution for body-mass index, weight and height in children of the Abruzzo region and to compare them with commonly used standards. STUDY DESIGN: Weight, height and body-mass index (BMI, weight/height2) were reported from 2858 school children (6 to 14 years old) of a town of Central Italy (Pescara). Data were detected in 1991. The conventional percentiles were calculated. Then we considered the first (25%), the median (50%) and the third (75%) quartile of all obtained data. Those of the BMI were superimposed on France (Rolland-cachera MF, Eur J Clin Nutr 1991;45:13) and USA (Hammer LD, Am J Dis Child 1991;145:259) standards. Those of weight and height were superimposed on the respective Tanner standards (Tanner JM, Arch Dis Child 1966;41:613). RESULTS: The percentiles are shown. The central point of distribution (quartiles) appear slid over. The nearer standard for BMI to our sample seems to be represented by France standards, in front of which our values result slid quite exactly of one quartile over. The comparison with USA standards shows an increase of our findings, but the slope of the curves is different (overall in the advanced ages). Both weight and height, compared with Tanner standards, show an increase of values. CONCLUSIONS: 1) Different growth patterns are observed in the studied sample; 2) to calculate the prevalence of wasting and fattening conditions using values of cutoff points from not own standards could load to not appropriate estimates. PMID- 7799886 TI - [Investigation of smoking habits in school-age subjects. Long-term results after a health education program]. PMID- 7799885 TI - [Liver pathology in juvenile obesity: significance of the disorder and clinical contribution]. PMID- 7799887 TI - [Fatal neonatal listeriosis after maternal infection acquired with ingestion of fresh home-made cheese]. AB - The authors report on a newborn admitted to the Intensive Care Unit of Gaslini Institute for serious respiratory insufficiency who died on the third day of life because of a sepsis due to Listeria monocytogenes. The authors focus on the patient's history and clinical picture and on the histological evaluation of the lesions observed. The importance of infection in pregnancy and the possible severe consequences of listeriosis on the foetus are underlined, stressing the need for early diagnosis and adequate treatment. PMID- 7799888 TI - [Autoimmune hemolytic anemia with cold antibodies and hemoglobinuria secondary to EBV infection]. AB - The infection caused by EBV can be followed by immunological complications. One of these is autoimmune hemolytic anemia that up to today has been observed during infective mononucleosis only a few times. The authors describe a patient with this rare complication of the EBV infection and discuss its main clinical, pathogenetic and laboratory aspects, with particular attention to the presence of hemoglobinuria and to the absence of anti-i-antibodies. The disease's evolution was spontaneously favorable. For this reason and for the possible risks secondary to transfusions and to other therapeutical interventions, the authors believe that in autoimmune hemolytic anemia a vigil wait is more opportune before beginning the therapy. PMID- 7799889 TI - [Aarskog syndrome. A case report]. AB - A case of Aarskog syndrome in a 10-year-old boy born to an epileptic woman is reported. Clinical features and genetics of the condition are reviewed. An underestimated incidence of the syndrome related to its mild phenotypical appearance is suggested. Finally the association between Aarskog syndrome and maternal epilepsy is discussed. PMID- 7799890 TI - [Pharmacologic treatment and atopic dermatitis]. AB - The role of etiology, pathogenesis and clinical symptoms in children with Atopic Dermatitis is evaluated. Eighteen patients with elimination diet were treated, without cow milk and egg, and with pharmacologic treatment (ketotiphene and cro molyn sodium) for two months. Dietary therapy and treatment however result in a large reduction in clinical symptoms in children affected with Atopic Dermatitis. PMID- 7799891 TI - [Diabetes, obesity, hypertension and the autonomic nervous system]. AB - Functional changes of the autonomic nervous system may represent a common pathophysiologic factor in the association between non insulin-dependent diabetes, obesity, and essential hypertension. In all these conditions a number of sympathetic and/or parasympathetic dysfunctions consistent with autonomic neuropathy or simply with functional adaptations to haemodynamic changes have been reported. Autonomic neuropathy is a well known diabetic complication which is responsible for some clinical aspects of different severity. Subtle sympathetic and parasympathetic abnormalities possibly affecting thermogenesis have been shown in obese people. An increased sympathetic activity has been proposed as one of the pathogenetic mechanisms of essential hypertension. Finally, the association between diabetes, obesity, hypertension and sympathetic overactivity could be explained by a common trans-membrane ionic disturbance with an increase of intracellular calcium and a decrease of both intracellular magnesium and pH. PMID- 7799892 TI - [Low levels of dehydroepiandrosterone sulfate in adult males with insulin dependent diabetes mellitus]. AB - Studies on animals and humans have suggested that dehydroepiandrosterone sulphate (DHEAS) has antiatherogenic effects. It has been hypothesized that insulin may have an atherogenic role and it has been reported recently that, surprisingly, DHEAS levels decreased in normal men and women during the hyperinsulinemic euglycemic technique. Since a hyperinsulinemia frequently occurs during insulin therapy in patients with insulin dependent diabetes mellitus (IDDM), the present work was undertaken to determine whether DHEAS serum concentrations were decreased in IDDM patients as compared to controls and if so, to discover the possible causes. To this, purpose, out of 805 outpatients afferent to our Diabetes Centre from 1989 to 1992, three groups were selected on the basis of the criteria described below. Known interferences with the DHEAS serum concentrations such as gender (all males), age (aged 20-40 years) and Body Mass Index (BMI < 30) were excluded. Group A (cross-sectional study) was made up of 15 IDDM patients on insulin treatment with good metabolic control (HbA1C < 8%); group B (control study) was made of 18 healthy subjects (these patients were selected also on the basis of their normal oral glucose tolerance test) and group C (longitudinal study) was made up of 7 IDDM patients who had been examined previously and who were on insulin treatment. METHODS: In all three groups serum concentrations of DHEAS, 17 OH progesterone (17 OHP), delta 4 androstenedione (A4) and cortisol (F) were measured. In 10 patients from group A and in 9 patients from group B the ACTH test (9.25 mg IM Synacthen) was administered and the same hormonal pattern was measured after 60 min. In group C the same hormonal evaluation was performed 5 +/- 2.8 months after commencement of insulin therapy. RESULTS: DHEAS serum concentrations were significantly decreased in group A (median 2.9; range 1.1-5.2 mumol/l) with respect to group B (median 5.7; range 3.0-9.5 mumol/l) (p < 0.0012). However, the serum concentrations of 17 OHP (median 3.9 nm/l; range 2.9 6.9 nm/l and A4 (median 5.2 nm/l; range 1.8-10.2 nm/l) were also significantly reduced, while cortisol levels and the 17 OHP/A4 ratio were comparable to group B. After administration of ACTH, the delta increment in cortisol percentage showed a frank increase (55.1%) in group A with respect to group B (33.1%) (p < 0.01). The rise in DHEAS showed a lower increase in group A (10.2%) with respect to group B (65.5%) even though not statistically significant, while the other hormones showed an overlap between the two groups. In group C the serum concentrations of hormones before insulin therapy did not show any statistical differences with respect to the values in group B. A second evaluation, which was performed during insulin therapy, showed that only the 17 OHP/A4 ratio tended towards higher values with respect to pretherapy values (1.1 and 0.6 respectively; p = 0.07). In conclusion our data confirm low DHEAS levels during chronic insulin administration therapy. The underlying mechanism could be a general aspecific reduction in the activity of P 450 C 21 SCC enzymes in contrast with the specific inhibition of 17.20-lyase obtained during insulin bolus. Whether the low serum concentrations of DHEAS can determine an atherogenic effect of insulin needs further investigation, but the hormone could constitute a new parameter for the follow-up of patients affected by diabetes mellitus. PMID- 7799894 TI - [Serum levels of the carboxyterminal telopeptide of type I collagen in patients with thyroid disorders]. AB - Serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) levels, marker of bone resorption, were evaluated in 35 patients with hyperthyroidism (age range: 21-68 years) and in 35 with hypothyroidism (age range: 28-69 years). Data obtained were compared with those recorded in an age and sex matched control group. In patients with hyperthyroidism, serum ICTP levels were significantly higher than in controls (mean +/- SE: 9.1 +/- 0.7 vs 4.1 +/- 0.3 ng/ml; p < 0.0001). In patients with untreated hypothyroidism ICTP levels were significantly reduced (2.5 +/- 0.2 ng/ml, p < 0.0001); seven patients with hypothyroidism, evaluated after substitutive L-thyroxine treatment, showed a significant increase of ICTP levels (6th month: 5.9 +/- 0.7 ng/ml, p < 0.02). Taking into consideration all the data recorded in patients with both hyper- and hypothyroidism, serum ICTP levels were positively correlated with those of free T3 and free T4 and negatively correlated with those of TSH. In conclusion, our data show that repeated determinations of ICTP levels, which directly reflect the bone resorption activity, might be usefully employed in the evaluation of bone turnover in patients with thyroid disorders. PMID- 7799893 TI - [ANP in the cirrhotic patient. A clinical contribution]. AB - Pathogenesis of ascites in patients affected by liver cirrhosis is still debated; humoral and haemodynamic factors can play a role. Plasmatic renin activity (PRA), plasmatic aldosterone (PA), atrial natriuretic peptide (ANP) plasma levels, blood Na, K, urea, urinary K and Na were evaluated in 14 patients affected by liver cirrhosis (11 males and 3 females, aged from 38 to 62 years), 8 of them with ascites. The results were compared with those obtained in a control group poised to age and sex to the experimental group. 4 out of 14 patients suffering from ascites unresponsive to medical treatment were submitted to peritoneal venous jugular shunt (PVGS) and blood samples for PRA, PA and ANP were withdrawn immediately before, 4, 8 hours following surgery. The patients affected by liver cirrhosis without ascites showed PRA and PA levels similar to those observed in the control group, while ANP plasma levels were significantly higher (50.6 + 9.6 vs. 39.7 + 9.5 Pg/ml) (p < 0.02). In patients with ascites ANP, PA and PRA levels were higher than those observed in non ascites patients (ANP = 147.8 + 97.3 vs. 50.6 + 9.6 pg/ml; PA = 20.6 + 2.7 vs 7.8 + 0.8 ng/dl; PRA = 4.48 + 0.5 vs 1.9 + 0.34 ng/ml/h). In patients submitted to PVGS, PA and PRA levels were reduced 4 and 8 hours following the surgery, while ANP levels showed significant increase. A natriuretic and diuretic response has been observed even in the absence of ANP plasma levels variations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799896 TI - [Circulating levels of CoQ10 in hypo- and hyperthyroidism]. AB - Coenzyme Q10 (CoQ10) plays an essential physiologic role in oxidative phosphorylation and its plasma and tissue concentration has been evaluated in various pathologic conditions, both endocrine and non endocrine; among the latter particularly in cardiac failure. Plasma CoQ10 determination has been reported in the literature an a useful diagnostic tool in differential diagnosis of thyroid diseases. In the present study we have evaluated CoQ10 circulating levels both in hypo- and hyperthyroidism. For this purpose plasma CoQ10, fT3-fT4 and TSH concentrations have been determined (HPLC, RIA and IRMA respectively) in a group of hypothyroid patients, hyperthyroid and control subjects. No patient was harbouring cardiovascular, metabolic or systemic disease. CoQ10 has resulted 0.97 +/- 0.46 mcg/ml in the hypothyroid group, 0.51 +/- 0.35 in hyperthyroid and 0.73 +/- 0.16 in control group, with a significative difference between first and second group only; more, the prevalence of high levels has appeared greater in hypo- towards hyperthyroid patients and that of low levels in the latter greater than in the former. Finally an inverse relation of CoQ10 with fT3 and tT3, but not with fT4 and tT4, has been shown. In conclusion, plasma CoQ10 levels have not given in this study a sharp distinction between euthyroidism on a side and hypo- and hyperthyroidism on the other, but necessity of longitudinal studies after therapy is outlined, both to know time of normalization of plasma concentrations and to verify the opportunity of exogenous administration of CoQ10 in hyperthyroid patients with risk factors for heart failure. PMID- 7799895 TI - [Serum levels of the tartrate-resistant isoenzyme, acid phosphatase, for the evaluation of bone remodeling in hyperthyroidism]. AB - Tartrate-resistant acid phosphatase (TRAP) is one of the acid phosphatase isoenzymes. It is secreted by osteoclasts so it has been proposed as a marker of bone resorption. Bone turnover is high in hyperthyroidism due to an increase in both bone resorption and formation. The aim of the study was to measure serum TRAP as well as other markers of bone metabolism in 20 fertile age females affected by Graves-disease; 11 patients were also studied after euthyroid state was attained by means of a 6 month course of methimazole treatment. TRAP was measured with the colorimetric method using p-nitrophenylphosphate as substrate. Free thyroid hormones, TSH, serum calcium (corrected for albumin concentration), phosphate, osteocalcin, alkaline phosphatase, parathormone intact molecule, and urinary excretions of calcium, phosphate and hydroxyproline were measured, too. Twenty-eight healthy fertile women made up the control group. Untreated patients had a significant increase of TRAP, osteocalcin, serum calcium, alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A significant fall in all these parameters but alkaline phosphatase was disclosed comparing patients before and after treatment, nevertheless only urinary calcium became not significantly different from the controls. TRAP showed a significant correlation with free T3 levels but not with hydroxyproline excretions. This survey on fertile age women with Graves' disease shows a significant increase in serum concentration of TRAP, which decreases, but doesn't get normalization, when euthyroidism is attained by a six month course of methimazole therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799897 TI - [Sclerotherapy of thyroid cysts with tetracycline hydrochloride]. AB - In order to verify sclerotherapy efficiency in solitary thyroid cysts, needle aspiration of the cyst followed by instillation of tetracycline hydrochloride into the cyst cavity was performed in 110 patients; in thirty of these the aspirations was ultrasonically guided. A tight dressing on the neck was applied for 48 hours in order to maintain pressure on the cyst cavity. All patients were treated with L-T4 in TSH-suppressive doses. In a few patients (< 155), the tetracycline instillation caused local pain, lasting less than two hours. In no case, did cytological examination of the sediment of the aspirated fluid reveal any evidence of malignant cells. In 82 patients (84.54% of the 97 controlled patients), the last ultrasonic follow-up (performed at 3, 6, 9, 12 or 24 months) showed a decrease in lesion size. In particular, 16 patients (16.50%) had a complete cyst disappearance, 41 patients (42.17%) had a volume reduction of the cyst between 85 and 65%, and in 25 patients (25.77%) the reduction was more than 25%. In the remaining 15 patients (15.46%) a second treatment was performed, 3 of them also required a third treatment but in all these cases, the results seemed to be less satisfactory. The distinction in cyst size seemed to indicate that in the case of a large cyst (> 36 mm diameter), the treatment gives better results (92% success rate against 82% of the other patients). In conclusion, we are able to affirm that needle aspiration of the thyroid cyst with instillation of tetracycline hydrochloride is a simple, well tolerated and low cost technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7799898 TI - [Iodine deficiency diseases and pregnancy]. AB - Iodine is a fundamental element of diet since it is important in thyroid hormone biosynthesis. Dietary iodine deficiency can provoke not only thyroid enlargement, but also symptoms and signs of hypothyroidism of various degree, known as "iodine deficiency disorders" (IDD). Thus, the iodine supplementation is mandatory. It can be obtained, in our regions, where subendemic deficiency is frequent, by adding iodine to salt. This is the only way to avoid anatomo-functional lesions, that are dramatic in pregnancy and childhood. PMID- 7799899 TI - [Clinical tolerability of methimazole]. PMID- 7799900 TI - Taking the pulse of medical technology. PMID- 7799901 TI - Minnesota public opinion on health care resource allocation. AB - Creating workable policies for allocating or rationing finite health care resources to meet the needs of individuals as well as the broader society vexes policymakers, providers, and consumers. This paper presents results of a March 1994 Lou Harris survey of 1,006 Minnesotans about health care allocation. Minnesotans believe that allocative or rationing decisions are inevitable and can be discussed. Individualized bedside allocative decisions are preferable to categorical or universal exclusions of some health care benefits. People want comprehensive health care and are willing to let sound clinical judgment, perhaps informed by practice guidelines, selectively withhold some services. The integrity of plan-based allocation or rationing may be best secured and safeguarded by standards that ensure that the decisions are based on patients' best interests, involve trusted clinical decision makers, and include lay participation in the decision making. PMID- 7799903 TI - Minnesota Medical Association Guaranteed Benefits Task Force Report. PMID- 7799904 TI - Rational rationing. PMID- 7799902 TI - Using technology appropriately. Challenges for Minnesota's Health Technology Advisory Committee. PMID- 7799905 TI - Educating your patients about health records--the new notice law. PMID- 7799907 TI - Time to confront health care rationing. PMID- 7799908 TI - Asthma--United States, 1982-1992. AB - Asthma is characterized by variable airflow obstruction with airway hyperresponsiveness; prominent clinical manifestations include wheezing and shortness of breath. During the 1980s, the prevalence of and mortality associated with asthma increased in the United States and other countries (1,2). To describe national trends in disease burden for asthma in the United States, CDC analyzed data for 1982-1992 (the most recent year for which data are available) for deaths, hospital discharges, and self-reported morbidity. This report summarizes the findings of the analysis. PMID- 7799906 TI - Oregon physician makes health care a political priority. PMID- 7799909 TI - Changes in notifiable diseases data presentation. AB - The next issue of MMWR (dated January 13, 1995 [volume 44, number 1]), will incorporate modifications to Tables I and II, Cases of Notifiable Diseases, United States. The purposes of these modifications are to improve the usefulness of notifiable diseases data (1,2) and to respond to changing priorities in notifiable disease surveillance. This report describes the rationale for data dissemination in Table I and Table II. PMID- 7799910 TI - Lack of evidence for wild poliovirus circulation--United States, 1993. AB - Following the isolation of wild poliovirus type 3 during January-February 1993 among members of a religious community objecting to vaccination in Alberta, Canada, surveillance for poliomyelitis was enhanced among related communities in the United States (1). In addition, during May-July 1993, a series of surveys was conducted in seven states (Iowa, Missouri, New York, Ohio, Pennsylvania, Washington, and Wisconsin) to determine whether wild poliovirus was circulating or had circulated recently among members of these religious communities residing in the states. This report summarizes the results of these surveys. PMID- 7799912 TI - Injuries associated with use of snowmobiles--New Hampshire, 1989-1992. AB - Recreational use of snowmobiles is popular in New Hampshire during the winter months; from 1982 to 1992, the annual number of registered snowmobiles ranged from approximately 21,200 to 42,500. During this period, 26 deaths associated with use of snowmobiles in New Hampshire accounted for 822 years of potential life lost before age 65 years. To assist in the development and evaluation of injury-prevention programs for users of off-highway recreational vehicles (OHRVs) (e.g., all-terrain vehicles, trail bikes, and snowmobiles), the State of New Hampshire Department of Fish and Game (DFG) and the New Hampshire Department of Health and Human Services examined reports of injuries resulting from OHRV use in New Hampshire from January 1989 through February 1992. This report summarizes information about snowmobile-associated fatal and nonfatal injuries during this period. PMID- 7799911 TI - Recommended childhood immunization schedule--United States, January 1995. Advisory Committee on Immunization Practices. American Academy of Pediatrics. American Academy of Family Physicians. National Immunization Program, CDC. PMID- 7799913 TI - Proportionate mortality from pulmonary tuberculosis associated with occupations- 28 states, 1979-1990. AB - The risk for occupational exposure to tuberculosis (TB) is increased among healthcare and other workers exposed to persons with active TB, workers exposed to silica or other agents that increase the risk of progression from latent infection to active TB, and workers in occupations associated with low socioeconomic status (SES). Accurate estimates of and surveillance for occupationally associated TB are limited because reports of incident TB cases lack comprehensive occupational data (1). Although occupation is routinely recorded on death certificates, this information is not routinely coded and entered into vital statistics data files. To identify occupations associated with increased risk for TB mortality, CDC's National Institute for Occupational Safety and Health (NIOSH) used data from the National Occupational Mortality Surveillance (NOMS) database to conduct a proportionate mortality study of persons with pulmonary TB by occupation for 1979-1990 (the most recent year for which data were available). This report presents the findings of the study. PMID- 7799914 TI - Physician vaccination referral practices and vaccines for children--New York, 1994. AB - Although vaccinations are among the most effective preventive public health measures available, many children are not vaccinated on time (1). One identified barrier to timely vaccination is referral of children by primary-care physicians to other medical settings for vaccination (2). This report summarizes a survey by the New York State Department of Health of vaccination referral practices among New York physicians and describes the implementation in New York of Vaccines for Children (VFC), a national program making federally purchased vaccines available at no cost to healthcare providers for administration to eligible children (3). PMID- 7799915 TI - Differences in maternal mortality among black and white women--United States, 1990. AB - The risk for maternal mortality has consistently been higher among black women than white women. The 1990 national health objective of reducing maternal mortality to no more than five deaths per 100,000 live births for any racial/ethnic group was nearly achieved for white women, for whom the maternal mortality ratio was 5.7 in 1990 (1); for black women, however, the ratio was 18.6. The year 2000 national health objectives include reducing the overall maternal mortality ratio to no more than 3.3 deaths per 100,000 live births and to no more than five for blacks (objective 14.3) (2). This report summarizes race specific differences in maternal mortality among black and white women for 1990 and compares these with trends in mortality from 1940-1990. PMID- 7799916 TI - Four structurally distinct, non-DNA-binding subunits of human nuclear respiratory factor 2 share a conserved transcriptional activation domain. AB - Nuclear respiratory factor 2 (NRF-2) was previously purified to near homogeneity from HeLa cells on the basis of its ability to bind tandem recognition sites in the rat cytochrome oxidase subunit IV (RCO4) promoter. It consisted of five subunits, alpha, beta 1, beta 2, gamma 1, and gamma 2. Sequencing of tryptic peptides from alpha and from mixtures of the two beta or two gamma subunits revealed sequence identities with subunits of the mouse GA-binding protein (GABP), a ubiquitously expressed ETS domain activator composed of three subunits, alpha, beta 1, and beta 2. To understand the precise relationship between NRF-2 and GABP, cDNAs for all five NRF-2 subunits have now been cloned and their products have been overexpressed. The results establish that the two additional NRF-2 subunits are molecular variants that differ from GABP beta 1 and beta 2 by having a 12-amino-acid insertion containing two serine doublets. PCR and RNase protection assays show that mRNAs for these variants are expressed in the human but not the rodent cells and tissues examined. The insertion did not alter the ability of the beta and gamma subunits to associate with alpha, the DNA-binding subunit, nor did it affect the ability of NRF-2 beta 1 or beta 2 to direct high affinity binding of alpha to tandem sites in the RCO4 promoter. In addition, the four NRF-2 beta and gamma subunits were equally proficient in activating transcription in transfected cells when fused to a GAL4 DNA-binding domain. The domain responsible for this transcriptional activation was localized by deletion mapping to a region of approximately 70 amino acids that is conserved in all four NRF-2 beta and gamma subunits. The repeated glutamine-containing hydrophobic clusters within this region bear a strong resemblance to those recently implicated in protein-protein interactions within the transcriptional apparatus. PMID- 7799917 TI - A novel cis-acting element required for lipopolysaccharide-induced transcription of the murine interleukin-1 beta gene. AB - Regulatory elements important for transcription of the murine interleukin-1 beta (IL-1 beta) gene lie within a DNase I-hypersensitive region located > 2,000 bp upstream from the transcription start site. We have identified within this region a novel positive regulatory element that is required for activation of an IL-1 beta promoter-chloramphenicol acetyltransferase (CAT) fusion gene in the murine macrophage line RAW264.7. Electrophoretic mobility shift analysis of the 3' portion (-2315 to -2106) of the hypersensitive region revealed at least two nuclear factor binding sites, one of which is located between positions -2285 and -2256. Competitive inhibition studies localized the binding site to a 15-bp sequence between -2285 and -2271. Nuclear factor binding was lost by mutation of the 6-bp sequence from -2280 to -2275. The specific retarded complex formed with RAW264.7 nuclear extract was not detected under similar conditions with nuclear extracts from RLM-11, a murine T-cell line which does not express IL-1 beta RNA. Mutation of the 6-bp sequence (-2280 to -2275) in the chimeric IL-1 beta promoter -4093 +I CAT plasmid virtually eliminated the activation of this reporter gene by lipopolysaccharide (LPS) in transfected RAW264.7 cells. Multimerization of the 15 bp sequence containing the core wild-type 6-bp sequence 5' of minimal homologous or heterologous promoters in CAT reporter plasmids resulted in significant enhancement of CAT expression compared with parallel constructs containing the mutant 6-bp core sequence. This element was LPS independent and position and orientation dependent. The multimerized 15-bp sequence did not enhance expression in RLM-11 cells. Methylation interference revealed contact residues from -2281 to -2271, CCAAAAAGGAA. Because a search of the NIH TFD data bank with the 11-bp binding site sequence found no homology to known nuclear factor binding sites, we have designated this sequence the IL1 beta -upstream nuclear factor 1 (IL1 beta UNF1) target. UV cross-linking and sodium dodecyl sulfate-polyacrylamide electrophoresis identified an IL1 beta -UNF1-specific binding factor approximately 85 to 90 kDa in size. PMID- 7799918 TI - An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis. AB - We carried out subtractive enrichment of a cDNA library derived from mRNA of senescent human diploid fibroblasts (HDF) established from a subject with Werner syndrome of premature aging. By differential screening, we isolated an overexpressed cDNA sequence (S1-5) that codes for a novel protein containing epidermal growth factor (EGF)-like domains which match the EGF-like consensus sequences within several known extracellular proteins that play a role in cell growth, development, and cell signalling. S1-5 mRNA is overexpressed in Werner syndrome and senescent normal HDF, is induced by growth arrest of young normal cells, but is significantly decreased by high serum, conditions which promote cellular proliferation. Paradoxically, microinjection into young HDF of two different lengths of S1-5 mRNA, containing different putative AUG translational start sites, consistently stimulated rather than inhibited DNA synthesis by an apparent autocrine/paracrine mechanism. Thus, the S1-5 gene product may represent a negative and/or positive factor whose ultimate activity is modulated by the cell environment as occurs with other members of EGF-like family. PMID- 7799919 TI - DNA-binding specificity of the cut repeats from the human cut-like protein. AB - The Drosophila Cut and mammalian Cut-like proteins contain, in addition to the homeodomain, three other DNA-binding regions called Cut repeats. Cut-like proteins, therefore, belong to a distinct class of homeodomain proteins with multiple DNA-binding domains. In this study, we assessed the DNA-binding specificity of the human Cut repeats by performing PCR-mediated random oligonucleotide selection with glutathione S-transferase fusion proteins. Cut repeat 1, Cut repeat 3, and Cut repeat 3 plus the homeodomain selected related yet distinct sequences. Therefore, sequences selected by one of the fusion proteins were often, but not always, recognized by the other proteins. Consensus binding sites were derived for each fusion protein. In each case, however, some selected sequences diverged from the consensus but were confirmed to be high affinity recognition sites by electrophoretic mobility shift assay. We conclude that Cut DNA-binding domains have broad, overlapping DNA-binding specificities. Determination of dissociation constants indicated that in addition to the core consensus, flanking sequences have a moderate but significant effect on sequence recognition. Evidence from electrophoretic mobility shift assay, DNase footprinting, and dissociation constant analyses strongly suggested that glutathione S-transferase/Cut fusion proteins bind to DNA as dimers. The implications of these findings are discussed in relation to the DNA-binding capabilities of Cut repeats. In contrast to other studies, we found that the human Cut-like protein does not preferably bind to a site that includes an ATTA homeodomain-binding motif. Here we demonstrate that the native human Cut-like protein recognizes more efficiently a site containing an ATCGAT core consensus flanked with G/C-rich sequences. PMID- 7799920 TI - Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. AB - Xenopus in vitro studies have implicated both transforming growth factor beta (TGF-beta) and fibroblast growth factor (FGF) families in mesoderm induction. Although members of both families are present during mouse mesoderm formation, there is little evidence for their functional role in mesoderm induction. We show that mouse embryonic stem cells, which resemble primitive ectoderm, can differentiate to mesoderm in vitro in a chemically defined medium (CDM) in the absence of fetal bovine serum. In CDM, this differentiation is responsive to TGF beta family members in a concentration-dependent manner, with activin A mediating the formation of dorsoanterior-like mesoderm and bone morphogenetic protein 4 mediating the formation of ventral mesoderm, including hematopoietic precursors. These effects are not observed in CDM alone or when TGF-beta 1, -beta 2, or -beta 3, acid FGF, or basic FGF is added individually to CDM. In vivo, at day 6.5 of mouse development, activin beta A RNA is detectable in the decidua and bone morphogenetic protein 4 RNA is detectable in the egg cylinder. Together, our data strongly implicate the TGF-beta family in mammalian mesoderm development and hematopoietic cell formation. PMID- 7799921 TI - Identification of the rel family members required for virus induction of the human beta interferon gene. AB - We have carried out experiments to determine which members of the rel family of transcription factors are involved in virus induction of the beta interferon (IFN beta) gene. First, we examined the inducibility of artificial DNA binding sites that preferentially interact with different homo- or heterodimeric combinations of rel proteins in vitro. We found that only those sites capable of binding the p50/p65 heterodimer are virus inducible. Second, we analyzed a series of mutant rel DNA-binding sites in the context of the intact IFN-beta promoter. We found a correlation between (i) sites capable of binding both the p50/p65 heterodimer and the high-mobility-group protein HMG I(Y) and (ii) virus inducibility. Third, cotransfection of the IFN-beta gene enhancer/promoter with plasmids capable of expressing several different rel proteins revealed that only the combination of p50 and p65 efficiently activated transcription. Finally, we have used antibodies directed against different rel proteins to show that virus-inducible protein-DNA complexes assembled on the IFN-beta enhancer in vitro contain both p50 and p65. We conclude that the p50/p65 heterodimer is responsible for the NF-kappa B dependent activation of the IFN-beta gene promoter in response to virus infection. PMID- 7799922 TI - Characterization of DNA synthesis and DNA-dependent ATPase activity at a restrictive temperature in temperature-sensitive tsFT848 cells with thermolabile DNA helicase B. AB - A temperature-sensitive mutant defective in DNA replication, tsFT848, was isolated from the mouse mammary carcinoma cell line FM3A. In mutant cells, the DNA-dependent ATPase activity of DNA helicase B, which is a major DNA-dependent ATPase in wild-type cells, decreased at the nonpermissive temperature of 39 degrees C. DNA synthesis in tsFT848 cells at the nonpermissive temperature was analyzed in detail. DNA synthesis measured by incorporation of [3H]thymidine decreased to about 50% and less than 10% of the initial level at 8 and 12 h, respectively. The decrease in the level of thymidine incorporation correlated with a decrease in the number of silver grains in individual nuclei but not with the number of cells with labeled nuclei. DNA fiber autoradiography revealed that the DNA chain elongation rate did not decrease even after an incubation for 10 h at 39 degrees C, suggesting that initiation of DNA replication at the origin of replicons is impaired in the mutant cells. The decrease in DNA-synthesizing ability coincided with a decrease in the level of the DNA-dependent ATPase activity of DNA helicase B. Partially purified DNA helicase B from tsFT848 cells was more heat sensitive than that from wild-type cells. Inactivation of DNA dependent ATPase activity of DNA helicase B from mutant cells was considerably reduced by adding DNA to the medium used for preincubation, indicating that the DNA helicase of mutant cells is stabilized by binding to DNA. PMID- 7799923 TI - DNA synthesis generally initiates outside the simian virus 40 core origin in vitro. AB - The nucleotide positions at which DNA synthesis initiates in vitro, in the vicinity of the simian virus 40 origin, have been determined. Start sites for DNA synthesis are greatly suppressed over the simian virus 40 core origin. Relatively weak start sites are detected over the 21-bp repeats and T-antigen-binding site I; distal to these regions, stronger start sites are detected. Thus, studies using a model system for eukaryotic DNA replication indicate that DNA synthesis events initiate, in general, outside the core origin. PMID- 7799924 TI - Thymidylate synthase binds to c-myc RNA in human colon cancer cells and in vitro. AB - Using an immunoprecipitation-reverse transcription-PCR technique, we characterized a thymidylate synthase (TS) ribonucleoprotein complex in cultured human colon cancer cells that consists of TS protein and the mRNA of the nuclear oncogene c-myc. TS protein is complexed in intact cells with the C-terminal coding region of c-myc mRNA that includes nucleotide positions 1625 to 1790. RNA electrophoretic gel mobility shift assays confirm a specific interaction between TS protein and c-myc mRNA and provide additional evidence that the C-terminal coding region represents an important cis-acting regulatory element. Further evidence demonstrates that the in vitro translational efficiency of c-myc mRNA is inhibited as a result of its direct interaction with TS protein. In addition, the presence of exogenous c-myc mRNA specifically relieves the inhibitory effects of TS protein on TS mRNA translation. PMID- 7799925 TI - Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1. AB - src family tyrosine kinases contain two noncatalytic domains termed src homology 3 (SH3) and SH2 domains. Although several other signal transduction molecules also contain tandemly occurring SH3 and SH2 domains, the function of these closely spaced domains is not well understood. To identify the role of the SH3 domains of src family tyrosine kinases, we sought to identify proteins that interacted with this domain. By using the yeast two-hybrid system, we identified p62, a tyrosine-phosphorylated protein that associates with p21ras GTPase activating protein, as a src family kinase SH3-domain-binding protein. Reconstitution of complexes containing p62 and the src family kinase p59fyn in HeLa cells demonstrated that complex formation resulted in tyrosine phosphorylation of p62 and was mediated by both the SH3 and SH2 domains of p59fyn. The phosphorylation of p62 by p59fyn required an intact SH3 domain, demonstrating that one function of the src family kinase SH3 domains is to bind and present certain substrates to the kinase. As p62 contains at least five SH3 domain-binding motifs and multiple tyrosine phosphorylation sites, p62 may interact with other signalling molecules via SH3 and SH2 domain interactions. Here we show that the SH3 and/or SH2 domains of the signalling proteins Grb2 and phospholipase C gamma-1 can interact with p62 both in vitro and in vivo. Thus, we propose that one function of the tandemly occurring SH3 and SH2 domains of src family kinases is to bind p62, a multifunctional SH3 and SH2 domain adapter protein, linking src family kinases to downstream effector and regulatory molecules. PMID- 7799926 TI - Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution. AB - The Alu repetitive family of short interspersed elements (SINEs) in primates can be subdivided into distinct subfamilies by specific diagnostic nucleotide changes. The older subfamilies are generally very abundant, while the younger subfamilies have fewer copies. Some of the youngest Alu elements are absent in the orthologous loci of nonhuman primates, indicative of recent retroposition events, the primary mode of SINE evolution. PCR analysis of one young Alu subfamily (Sb2) member found in the low-density lipoprotein receptor gene apparently revealed the presence of this element in the green monkey, orangutan, gorilla, and chimpanzee genomes, as well as the human genome. However, sequence analysis of these genomes revealed a highly mutated, older, primate-specific Alu element was present at this position in the nonhuman primates. Comparison of the flanking DNA sequences upstream of this Alu insertion corresponded to evolution expected for standard primate phylogeny, but comparison of the Alu repeat sequences revealed that the human element departed from this phylogeny. The change in the human sequence apparently occurred by a gene conversion event only within the Alu element itself, converting it from one of the oldest to one of the youngest Alu subfamilies. Although gene conversions of Alu elements are clearly very rare, this finding shows that such events can occur and contribute to specific cases of SINE subfamily evolution. PMID- 7799927 TI - Position-independent transgene expression mediated by boundary elements from the apolipoprotein B chromatin domain. AB - The human apolipoprotein B (apoB) gene resides within a 47.5-kb chromatin domain that is flanked by sequences that bind to the nuclear matrix. These matrix attachment regions (MARs) are boundaries between nuclease-sensitive and resistant chromatin. As domain boundaries are thought to function as insulator elements, shielding sequences between them from effects of neighboring chromatin, this raised the possibility that the apoB MARs have functions that could be assayed by transfection. To test this possibility, we examined effects of the apoB MARs on transgene expression in transiently and stably transfected rat and human hepatoma cells. The apoB MARs had no effects on expression of transiently transfected reporters, but they altered expression of stably integrated transgenes in dramatic and reproducible ways. Single integrated copies of transgenes that contained the apoB promoter and second intron enhancer, which are sufficient for high-level expression in transient assays, were expressed at low and variable levels in stable transfectant clones. In contrast, transgenes containing the apoB 5' and 3' MARs were expressed at levels nearly 200-fold higher than levels of the minimal reporters in stable transfectants, and expression was position independent. Transgenes that contained the apoB MARs and an additional 3.3 kb of apoB 5' flanking sequence were also expressed in an elevated, position-independent manner. Surprisingly, tandem transgene arrays in multicopy transfectants were transcriptionally inactive. These observations suggest that the apoB MARs function as insulator elements, shielding transgene expression from effects of neighboring chromatin domains. PMID- 7799928 TI - Functional analysis of Met4, a yeast transcriptional activator responsive to S adenosylmethionine. AB - Transcription of the genes necessary for sulfur amino acid biosynthesis in Saccharomyces cerevisiae is dependent on Met4, a transcriptional activator that belongs to the basic region-leucine zipper protein family. In this report, we show that one mechanism permitting the repression of the sulfur network by S adenosylmethionine (AdoMet) involves inhibition of the transcriptional activation function of Met4. Using a wide array of deleted LexA-Met4 fusion proteins as well as various Gal4-Met4 hybrids, we identify the functional domains of Met4 and characterize their relationship. Met4 appears to contain only one activation domain, located in its N-terminal part. We demonstrate that this activation domain functions in a constitutive manner and that AdoMet responsiveness requires a distinct region of Met4. Furthermore, we show that when fused to a heterologous activation domain, this inhibitory region confers inhibition by AdoMet. Met4 contains another distinct functional domain that appears to function as an antagonist of the inhibitory region when intracellular AdoMet is low. On the basis of the presented results, a model for intramolecular regulation of Met4 is proposed. PMID- 7799931 TI - The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression. AB - L7 is expressed in all adult cerebellar Purkinje cells, although during development it appears in a stereotyped spatial and temporal pattern that is manifested as parasagittal domains of neurons. Mutations of the L7 promoter in transgenic mice have established that these domains represent functional compartments of Purkinje neurons. Therefore, it is hoped that by defining the transcriptional control of the L7 gene insights into the mechanisms that control functional fate and organization in the nervous system can be gained. Fragments of the L7 promoter were introduced into a selectable reporter gene in Saccharomyces cerevisiae, and these strains were used to select for cerebellar cDNAs encoding proteins that can bind to, and activate transcription from, these elements. This assay identified the c-Maf proto-oncogene as activating transcription from two sites in the L7 promoter. We did a functional domain analysis of vertebrate c-Maf based upon transcriptional activation in S. cerevisiae and showed the requirement for a transactivation domain, leucine zipper, and DNA-binding region in c-Maf. The c-Maf interaction site was mapped to the sequence G/TGG/CNG/TNCT CAGNN in the L7 promoter, which represents an atypical 12-O-tetradecanoate-13-acetate-responsive element-type Maf-responsive element. However, neither Fos nor Jun, either alone or in combination with each other or c-Maf, altered transcription from this element. In contrast, a Maf related protein, Nrl, completely mimicked c-Maf actions. These data suggest that Maf may interact with additional basic-zipper proteins that determine a subtype of Maf-responsive element binding. PMID- 7799930 TI - Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs. AB - Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the first and rate-limiting step in degradation of IGF-II mRNAs. Two sequence elements within the 3' untranslated region are required for cleavage: element I, located approximately 2 kb upstream of the cleavage site, and element II, encompassing the cleavage site itself. We have identified a stable double stranded RNA stem structure (delta G = -100 kcal/mol [418.4 kJ/mol]) that can be formed between element I and a region downstream of the cleavage site in element II. This structure is conserved among human, rat, and mouse mRNAs. Detailed analysis of the requirements for cleavage shows that the relative position of the elements is not essential for cleavage. Furthermore, the distance between the coding region and the cleavage site does not affect the cleavage reaction. Mutational analysis of the long-range RNA-RNA interaction shows that not only the double-stranded character but also the sequence of the stable RNA stem is important for cleavage. PMID- 7799929 TI - Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression. AB - The tumor suppressor gene product p53 can activate and repress transcription. Both transcriptional activation and repression are thought to involve the direct interaction of p53 with the basal transcriptional machinery. Previous work has demonstrated an in vitro interaction between p53 and the TATA-binding protein that requires amino acids 20 to 57 of p53 and amino acids 220 to 271 of the TATA binding protein. The present results show that a 75-amino-acid segment from the carboxy terminus of p53 also can bind to the TATA-binding protein in vitro, and this interaction requires amino acids 217 to 268 of the TATA-binding protein, essentially the same domain that is required for interaction with the amino terminal domain of p53. A carboxy-terminal segment of p53 can mediate repression when bound to DNA as a GAL4-p53 fusion protein. The amino- and carboxy-terminal p53 interactions occur within the domain on the TATA-binding protein to which the adenovirus 13S E1A oncoprotein has previously been shown to bind. The 13S E1A oncoprotein can dissociate the complex formed between the carboxy-terminal domain of p53 and the TATA-binding protein and relieve p53-mediated transcriptional repression. These results demonstrate that two independent domains of p53 can potentially interact with the TATA-binding protein, and they define a mechanism- relief of repression--by which the 13S E1A oncoprotein can activate transcription through the TATA motif. PMID- 7799932 TI - Mouse retinoid X receptor contains a separable ligand-binding and transactivation domain in its E region. AB - Steroid, thyroid, and retinoid hormones exert their biological functions by interacting with their cognate nuclear receptors. Upon binding receptors, hormones induce a protease-resistant structural change in the receptor ligand binding domain and subsequently activate the receptors. Utilizing partial proteolysis, we have been able to delineate a region in the mouse retinoid X receptor beta (mRXR beta) required for ligand binding. A separable activation domain within the mRXR beta E region has been identified. The activation domain, which is 21 amino acids in length, is located at the extreme C terminus of mRXR beta. This domain is not required for ligand binding since removal of this sequence neither eliminates the ligand-induced, protease-resistant conformational change nor alters the ligand-enhanced DNA binding. Furthermore, deletion of this activation domain converts the receptor into a transcriptional silencer. Finally, a further truncation of 9 amino acids (for a total of 30 amino acids) from the C terminus results in a mutant which does not undergo the protease-resistant conformational change and cannot bind DNA as a homodimer. Nevertheless, this mutant is still able to form a heterodimer with the thyroid hormone receptor. Therefore, homodimerization and heterodimerization can be distinguished by this nine-amino-acid sequence. PMID- 7799933 TI - Mouse mammary tumor virus chromatin in human breast cancer cells is constitutively hypersensitive and exhibits steroid hormone-independent loading of transcription factors in vivo. AB - We have stably introduced a reporter gene under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) into human T47D breast cancer cells to study the action of the progesterone receptor (PR) on transcription from a chromatin template. Unexpectedly, the chromatin organization of the MMTV LTR in these human breast cancer cells differed markedly from what we have observed previously. The region adjacent to the transcription start site (-221 to -75) was found to be constitutively hypersensitive to restriction enzyme cleavage in the absence of hormone. This region is normally encompassed within the second nucleosome of a phased array of six nucleosomes that is assembled when the MMTV LTR is stably maintained in mouse cells. Characteristically, in these rodent cells, the identical DNA sequences show increased restriction enzyme cleavage only in the presence of glucocorticoid. The increased access of restriction enzymes observed in the human PR+ cells was not observed in adjacent nucleosomes and was unaffected by treatment with the progesterone antagonist RU486. In addition, exonuclease III-dependent stops corresponding to the binding sites for nuclear factor 1 and the PR were observed before and after hormone treatment. These results indicate that MMTV chromatin replicated in these cells is organized into a constitutively open architecture and that this open chromatin state is accompanied by hormone-independent loading of a transcription factor complex that is normally excluded from uninduced chromatin. PMID- 7799934 TI - Cloning and characterization of FAD1, the structural gene for flavin adenine dinucleotide synthetase of Saccharomyces cerevisiae. AB - The FAD1 gene of Saccharomyces cerevisiae has been selected from a genomic library on the basis of its ability to partially correct the respiratory defect of pet mutants previously assigned to complementation group G178. Mutants in this group display a reduced level of flavin adenine dinucleotide (FAD) and an increased level of flavin mononucleotide (FMN) in mitochondria. The restoration of respiratory capability by FAD1 is shown to be due to extragenic suppression. FAD1 codes for an essential yeast protein, since disruption of the gene induces a lethal phenotype. The FAD1 product has been inferred to be yeast FAD synthetase, an enzyme that adenylates FMN to FAD. This conclusion is based on the following evidence. S. cerevisiae transformed with FAD1 on a multicopy plasmid displays an increase in FAD synthetase activity. This is also true when the gene is expressed in Escherichia coli. Lastly, the FAD1 product exhibits low but significant primary sequence similarity to sulfate adenyltransferase, which catalyzes a transfer reaction analogous to that of FAD synthetase. The lower mitochondrial concentration of FAD in G178 mutants is proposed to be caused by an inefficient exchange of external FAD for internal FMN. This is supported by the absence of FAD synthetase activity in yeast mitochondria and the presence of both extramitochondrial and mitochondrial riboflavin kinase, the preceding enzyme in the biosynthetic pathway. A lesion in mitochondrial import of FAD would account for the higher concentration of mitochondrial FMN in the mutant if the transport is catalyzed by an exchange carrier. The ability of FAD1 to suppress impaired transport of FAD is explained by mislocalization of the synthetase in cells harboring multiple copies of the gene. This mechanism of suppression is supported by the presence of mitochondrial FAD synthetase activity in S. cerevisiae transformed with FAD1 on a high-copy-number plasmid but not in mitochondrial of a wild-type strain. PMID- 7799936 TI - An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells. AB - One of the most widely used antitumor drugs is cis-diamminedichloroplatinum(II) (cisplatin), and mechanisms of cisplatin resistance have been investigated in numerous model systems. Many studies have used mouse leukemia L1210/0 as a reference wild-type cell line, and cisplatin-resistant subclones have been derived from it. Increased DNA excision repair capacity is thought to play a key role in the acquired cisplatin resistance, and this has influenced development of drugs for clinical trials. We report here that the L1210/0 line is in fact severely deficient in nucleotide excision repair of damaged DNA in vivo and in vitro. L1210/0 cell extracts could be complemented by extracts from repair defective human xeroderma pigmentosum (XP) or rodent excision repair cross complementing (ERCC) mutant cells, except for XPG/ERCC5 mutants. Purified XPG protein could restore repair proficiency to L1210/0 extracts. Expression of mouse XPG mRNA was similar in all L1210 lines studied, suggesting a point mutation or small alteration of XPG in L1210/0 cells. The DNA repair capacity of a cisplatin resistant subline, L1210/DDP10, is similar to that of type culture collection L1210 cells and to those of other normal mammalian cell lines. Nucleotide excision repair of DNA is thus clearly important in the intrinsic cellular defense against cisplatin. However, in contrast to what is generally believed, enhancement of DNA repair above the normal level in these rodent cells does not appear to be a mechanism of acquired resistance to the drug. PMID- 7799937 TI - Pulling the ribosome out of frame by +1 at a programmed frameshift site by cognate binding of aminoacyl-tRNA. AB - Programmed translational frameshifts efficiently alter a translational reading frame by shifting the reading frame during translation. A +1 frameshift has two simultaneous requirements: a translational pause which occurs when either an inefficiently recognized sense or termination codon occupies the A site, and the presence of a special peptidyl-tRNA occupying the P site during the pause. The special nature of the peptidyl-tRNA reflects its ability to slip +1 on the mRNA or to facilitate binding of an incoming aminoacyl-tRNA out of frame in the A site. This second mechanism suggested that in some cases the first +1 frame tRNA could have an active role in frameshifting. We found that overproducing this tRNA can drive frameshifting, surprisingly regardless of whether frameshifting occurs by peptidyl-tRNA slippage or out-of-frame binding of aminoacyl-tRNA. This finding suggests that in both cases, the shift in reading frame occurs coincident with formation of a cognate codon-anticodon interaction in the shifted frame. PMID- 7799935 TI - Affinity enrichment and functional characterization of TRAX1, a novel transcription activator and X1-sequence-binding protein of HLA-DRA. AB - The promoters of all class II major histocompatibility (MHC) genes contain a positive regulatory motif, the X element. The DNA-binding proteins specific for this element are presumed to play a critical role in gene expression, although there is a paucity of functional studies supporting this role. In this study, the X-box-binding proteins of HLA-DRA were affinity purified from HeLa nuclear extracts. Fractions 46 to 48 contained an X-box-binding activity and were determined by electrophoretic mobility shift assays to be specific for the X1 element. This X1 sequence-binding-protein, transcriptional activator X1 (TRAX1), was shown to be a specific transcriptional activator of the HLA-DRA promoter in an in vitro transcription assay. By UV cross-linking analysis, the approximate molecular mass of TRAX1 including the bound DNA was determined to be 40 kDa. When the TRAX1 complex was incubated with antibodies against a known recombinant X-box binding protein, RFX1, and tested in electrophoretic mobility shift assays, TRAX1 was neither shifted nor blocked by the antibody. Further analysis with methylation interference showed that TRAX1 bound to the 5' end of the X1 sequence at -109 and -108 and created hypersensitive sites at -114, -113, and -97. This methylation interference pattern is distinct from those of the known X1-binding proteins RFX1, RFX, NF-Xc, and NF-X. Taken together, our results indicate that TRAX1 is a novel X1-sequence-binding protein and transcription activator of HLA DRA. PMID- 7799939 TI - A new platelet-derived growth factor-regulated genomic element which binds a serine/threonine phosphoprotein mediates induction of the slow immediate-early gene MCP-1. AB - The MCP-1 chemokine gene belongs to a cohort of immediate-early genes that are induced with slower kinetics than c-fos. In this study, we identified a cluster of four platelet-derived growth factor (PDGF)-responsive elements within a 240-bp enhancer found in the distal 5' flanking MCP-1 sequences. Two of the elements bind one or more forms of the transcription factor NF-kappa B. We focused on the other two elements which are hitherto unreported, PDGF-regulated genomic motifs. One of these novel elements, detected as a 28-mer by DNase I footprinting, restores PDGF inducibility when added in two copies to a 5' truncated MCP-1 gene. A single copy of the second novel element, a 27-mer, restores PDGF inducibility to a 5' truncated MCP-1 gene. The 27-base element interacts with a PDGF-activated serine/threonine phosphoprotein that is detected only within the nucleus of PDGF treated 3T3 cells. DNA binding of this phosphoprotein is activated by PDGF treatment with slow kinetics that match the time course of MCP-1 gene expression, and activation is not inhibited by cycloheximide. PDGF-activated binding to the 27-mer is shown to involve a single 30-kDa protein by UV-cross-linking analysis. PMID- 7799938 TI - Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene. AB - Primary fibroblasts from patients with the genetic disease Fanconi anemia, which are hypersensitive to cross-linking agents, were used to screen a cDNA library for sequences involved in their abnormal cellular response to a cross-linking challenge. By using library partition and microinjection of in vitro-transcribed RNA, a cDNA clone, pSPHAR (S-phase response), which is able to correct the permanent repression of semiconservative DNA synthesis rates characteristic of these cells, was isolated. Wild-type SPHAR mRNA is expressed in all fibroblasts so far analyzed, including those of Fanconi anemia patients. Correction of the abnormal response in these cells appears therefore to be due to overexpression after cDNA transfer rather than to genetic complementation. The cDNA contains an open reading frame coding for a polypeptide of 7.5 kDa. Rabbit antiserum directed against a SPHAR peptide detects a protein of 7.9 kDa in Western blots (immunoblots) of whole-cell extracts from proliferating, but not resting, fibroblasts. The deduced amino acid sequence of SPHAR contains a motif found in the cyclins, and it is proposed that SPHAR acts within the injected cell by interfering with the cyclin-controlled maintenance of S phase. In agreement with this proposal, normal cells transfected with an antisense SPHAR expression vector have a significantly reduced rate of DNA synthesis during S phase and a prolonged G2 phase, reflecting the need for postreplicative DNA processing before entry into mitosis. PMID- 7799940 TI - The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2. AB - The interaction of the retinoblastoma susceptibility gene product (Rb)-related p107 protein with the E2F transcription factor in S-phase cells facilitates the formation of a multicomponent complex also containing cyclin A and the p33cdk2 kinase. We have created a series of p107 mutants to assess the ability of p107 to inhibit E2F function and the role of the cyclin A/cdk2 complex in this process. We find that p107 mutants that do not bind to E2F also fail to repress E2F dependent transcription. Moreover, we find that the ability of p107 to suppress E2F-dependent transcription is not dependent on the ability of p107 to associate with cyclin A/cdk2. Finally, an analysis of the ability of the p107 mutant proteins to suppress cell growth suggests that both E2F-dependent and E2F independent events correlate with this activity. PMID- 7799941 TI - Effects of phosphorylation by CAK on cyclin binding by CDC2 and CDK2. AB - The cyclin-dependent protein kinases (CDKs) are activated by association with cyclins and by phosphorylation at a conserved threonine residue by the CDK activating kinase (CAK). We have studied the binding of various human CDK and cyclin subunits in vitro, using purified proteins derived from baculovirus infected insect cells. We find that most CDK-cyclin complexes known to exist in human cells (CDC2-cyclin B, CDK2-cyclin A, and CDK2-cyclin E) form with high affinity in the absence of phosphorylation or other cellular components. One complex (CDC2-cyclin A) forms with high affinity only after CAK-mediated phosphorylation of CDC2 at the activating threonine residue. CDC2 does not bind with high affinity to cyclin E in vitro, even after phosphorylation of the CDC2 subunit. Thus, phosphorylation is of varying importance in the formation of high affinity CDK-cyclin complexes. PMID- 7799942 TI - Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes. AB - Alternative initiations of translation of the human fibroblast growth factor 2 (FGF-2) mRNA, at three CUG start codons and one AUG start codon, result in the synthesis of four isoforms of FGF-2. This process has important consequences on the fate of FGF-2: the CUG-initiated products are nuclear and their constitutive expression is able to induce cell immortalization, whereas the AUG-initiated product, mostly cytoplasmic, can generate cell transformation. Thus, the different isoforms probably have distinct targets in the cell. We show here that translation initiation of the FGF-2 mRNA breaks the rule of the cap-dependent ribosome scanning mechanism. First, translation of the FGF-2 mRNA was shown to be cap independent in vitro. This cap-independent translation required a sequence located between nucleotides (nt) 192 and 256 from the 5' end of the 318-nt-long 5' untranslated region. Second, expression of bicistronic vectors in COS-7 cells indicated that the FGF-2 mRNA is translated through a process of internal ribosome entry mediated by the mRNA leader sequence. By introducing additional AUG codons into the RNA leader sequence, we localized an internal ribosome entry site to between nt 154 and 318 of the 5' untranslated region, just upstream of the first CUG. The presence of an internal ribosome entry site in the FGF-2 mRNA suggests that the process of internal translation initiation, by controlling the expression of a growth factor, could have a crucial role in the control of cell proliferation and differentiation. PMID- 7799943 TI - PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. AB - Phosphoenolpyruvate carboxykinase (PEPCK) is expressed at high levels in liver, kidney, and adipose tissue. This enzyme catalyzes the rate-limiting step in hepatic and renal gluconeogenesis and adipose glyceroneogenesis. The regulatory factors important for adipose expression of the PEPCK gene are not well defined. Previous studies with transgenic mice established that the region between bp 2086 and -888 is required for expression in adipose tissue but not for expression in liver or kidney tissue. We show here that a DNA fragment containing this region can function as an enhancer and direct differentiation-dependent expression of a chloramphenicol acetyltransferase gene from a heterologous promoter in cultured 3T3-F442A preadipocytes and adipocytes. We further demonstrate that the adipocyte-specific transcription factor PPAR gamma 2, previously identified as a regulator of the adipocyte P2 enhancer, binds in a heterodimeric complex with RXR alpha to the PEPCK 5'-flanking region at two sites, termed PCK1 (bp -451 to -439) and PCK2 (bp -999 to -987). Forced expression of PPAR gamma 2 and RXR alpha activates the PEPCK enhancer in non adipose cells. This activation is potentiated by peroxisome proliferators and fatty acids but not by 9-cis retinoic acid. Mutation of the PPAR gamma 2 binding site (PCK2) abolishes both the activity of the enhancer in adipocytes and its ability to be activated by PPAR gamma 2 and RXR alpha. These results establish a role for PPAR gamma 2 in the adipose expression of the PEPCK gene and suggest that this factor functions as a coordinate regulator of multiple adipocyte specific genes. PMID- 7799944 TI - Two functionally distinct RNA-binding motifs in the regulatory domain of the protein kinase DAI. AB - The RNA-binding domain of the protein kinase DAI, the double-stranded RNA inhibitor of translation, contains two repeats of a motif that is also found in a number of other RNA-binding proteins. This motif consists of 67 amino acid residues and is predicted to contain a positively charged alpha helix at its C terminus. We have analyzed the effects of equivalent single amino acid changes in three conserved residues distributed over each copy of the motif. Mutants in the C-terminal portion of either repeat were severely defective, indicating that both copies of the motif are essential for RNA binding. Changes in the N-terminal and central parts of the motif were more debilitating if they were made in the first motif than in the second, suggesting that the first motif is the more important for RNA binding and that the second motif is structurally more flexible. When the second motif was replaced by a duplicate of the first motif, the ectopic copy retained its greater sensitivity to mutation, implying that the two motifs have distinct functions with respect to the process of RNA binding. Furthermore, the mutations have the same effect on the binding of double-stranded RNA and VA RNA, consistent with the existence of a single RNA-binding domain for both activating and inhibitory RNAs. PMID- 7799945 TI - Structural requirements for double-stranded RNA binding, dimerization, and activation of the human eIF-2 alpha kinase DAI in Saccharomyces cerevisiae. AB - The protein kinase DAI is activated upon viral infection of mammalian cells and inhibits protein synthesis by phosphorylation of the alpha subunit of translation initiation factor 2 (eIF-2 alpha). DAI is activated in vitro by double-stranded RNAs (dsRNAs), and binding of dsRNA is dependent on two copies of a conserved sequence motif located N terminal to the kinase domain in DAI. High-level expression of DAI in Saccharomyces cerevisiae cells is lethal because of hyperphosphorylation of eIF-2 alpha; at lower levels, DAI can functionally replace the protein kinase GCN2 and stimulate translation of GCN4 mRNA. These two phenotypes were used to characterize structural requirements for DAI function in vivo, by examining the effects of amino acid substitutions at matching positions in the two dsRNA-binding motifs and of replacing one copy of the motif with the other. We found that both copies of the dsRNA-binding motif are required for high level kinase function and that the N-terminal copy is more important than the C terminal copy for activation of DAI in S. cerevisiae. On the basis of these findings, we conclude that the requirements for dsRNA binding in vitro and for activation of DAI kinase function in vivo closely coincide. Two mutant alleles containing deletions of the first or second binding motif functionally complemented when coexpressed in yeast cells, strongly suggesting that the active form of DAI is a dimer. In accord with this conclusion, overexpression of four catalytically inactive alleles containing different deletions in the protein kinase domain interfered with wild-type DAI produced in the same cells. Interestingly, three inactivating point mutations in the kinase domain were all recessive, suggesting that dominant interference involves the formation of defective heterodimers rather than sequestration of dsRNA activators by mutant enzymes. We suggest that large structural alterations in the kinase domain impair an interaction between the two protomers in a DAI dimer that is necessary for activation by dsRNA or for catalysis of eIF-2 alpha phosphorylation. PMID- 7799947 TI - ST-1, a 39-kilodalton protein in Trypanosoma brucei, exhibits a dual affinity for the duplex form of the 29-base-pair subtelomeric repeat and its C-rich strand. AB - In our attempt to identify telomere region-binding proteins in Trypanosoma brucei, we identified ST-1, a polypeptide with novel features. ST-1 was chromatographically purified from S-100 cell extracts and was renatured from a sodium dodecyl sulfate-protein gel as a 39-kDa polypeptide. It forms a specific complex with the trypanosome telomere repeats of TTAGGG, but more significantly, it shows a higher affinity for the 29-bp subtelomere repeats of T. brucei. These 29-mer boxes are a large tandem series of telomere-derived repeats which separate the simple telomere DNA from middle-repetitive telomere-associated sequences on many chromosomes. ST-1 is the first example of a protein binding within such large repetitive subtelomere elements in trypanosomes or other organisms. ST-1 is also novel in that it has a selective affinity for the C-rich strands of both the subtelomeric 29-mer and the telomere repeats, comparable to that for the duplex form of the respective repeats. All previously described telomere-binding proteins have affinity for only the duplex form or for the G-rich strand. This C rich strand binding specificity of ST-1 may provide insight into this protein's mechanism of binding in vivo. PMID- 7799946 TI - A dominant-negative mutant of mSOS1 inhibits insulin-induced Ras activation and reveals Ras-dependent and -independent insulin signaling pathways. AB - The role of the Grb2-SOS complex in insulin signal transduction was investigated with a deletion mutant of mSOS1 that lacks the guanine nucleotide exchange domain of the wild-type protein. Cells over-expressing either wild-type (CHO-IR/SOS cells) or mutant (CHO-IR/delta SOS cells) mSOS1 were established by transfection of Chinese hamster ovary cells that express human insulin receptors (CHO-IR cells) with the appropriate expression plasmid. The mutant mSOS1 protein did not contain the guanine nucleotide exchange activity in vitro and associated with Grb2 both in vivo and in vitro. In both CHO-IR and CHO-IR/SOS cells, insulin rapidly stimulated the formation of GTP-bound Ras and the phosphorylation of mitogen-activated protein (MAP) kinase; both these effects of insulin were markedly inhibited in CHO-IR/delta SOS cells. Insulin-induced glycogen synthase and 70-kDa S6 kinase activities were not affected by expression of either wild type or mutant mSOS1. These results show that the mutant mSOS1 acts in a dominant negative manner and suggest that the Grb2-SOS complex mediates, at least in part, insulin-induced activation of Ras in intact cells. The data also indicate that Ras activation is not required for insulin-induced stimulation of glycogen synthase and 70-kDa S6 kinase. PMID- 7799949 TI - Expression of the chicken beta-globin gene cluster in mice: correct developmental expression and distributed control. AB - To investigate the regulation of gene clusters, we introduced the entire chicken beta-globin cluster into mice. This 35-kb region includes the four globin genes (rho-beta H-beta A-epsilon), the four upstream hypersensitive sites, and the intergenic beta A/epsilon enhancer. The chicken globins are not arranged in order of developmental expression, which is unlike the case for the human beta-globin cluster, in which gene order plays a role in the regulation of globin expression. Mice carrying the chicken cluster expressed the transgenes with the same developmental patterns as seen in the chicken. Therefore, stage-specific erythroid transcriptional milieus existed before the divergence of birds and mammals and have been conserved since then. Mice bearing the complete cluster except for a deletion removing the beta A/epsilon enhancer displayed markedly reduced expression of the beta H, beta A, and epsilon genes with efficient (but variable) rho expression. Mice carrying the four genes and beta A/epsilon enhancer but without the upstream hypersensitive sites showed reduced expression of rho, beta H, and beta A, with variable expression of epsilon. We conclude that (i) all of the genes (except possibly rho) are under the control of both the upstream hypersensitive sites and the enhancer, (ii) the influence of the control elements can extend beyond the nearest active gene, (iii) a single element (the enhancer) can influence more than one gene in a single developmental stage, (iv) the enhancer can work bidirectionally, and (v) neither the upstream sites (as a group) nor the enhancer showed developmental stage specificity. Thus, the regulation of this cluster is achieved by interaction of two distinct control regions with each of the globin genes. PMID- 7799948 TI - Raf-1 N-terminal sequences necessary for Ras-Raf interaction and signal transduction. AB - Raf-1 is a serine/threonine protein kinase that transduces signals from cell surface receptors to the nucleus. Interaction of Ras with a regulatory domain in the N-terminal half of Raf-1 is postulated to regulate Raf-1 protein kinase and signaling activities. To better understand molecular interactions of Ras with Raf 1 and regulation of the Raf-1 kinase, a panel of Raf-1 N-terminal mutants expressed in the baculovirus-insect cell system was used for mapping the precise region necessary for Ras interaction in the context of full-length, functional Raf-1 kinase. An 80-amino-acid sequence in Raf-1 between positions 53 and 132 was found to confer the ability to bind Ras protein in vitro and in infected insect cells. Deletion of residues 53 to 132 abolished Raf-1 kinase activation by Ras in insect cells, indicating that activation of the Raf-1 kinase by Ras requires the capacity to physically interact with Ras. By contrast, deletion of this Ras binding site did not diminish activation of Raf-1 kinase by Src, implying that Src and Ras can activate Raf-1 through independent mechanisms. Significantly, Raf 1 mutants lacking the entire zinc finger motif or containing substitutions of two critical cysteine residues in the zinc finger retained the ability to bind Ras and to be activated by this interaction. Consistent with results obtained in the baculovirus-insect cell system, deletion of residues 53 to 132 but not mutations in the zinc finger motif abrogated the ability of kinase-inactive, dominant negative Raf-1 to block Ras-mediated signaling in Xenopus oocytes. Together, these results provide evidence that the direct physical interaction of Ras with Raf-1 amino acids 53 to 132 is required for activation of the Raf-1 kinase and signaling activities by Ras but not by Src. Furthermore, the adjacent zinc finger motif in Raf-1 is not essential either for interaction with Ras or for activation of the Raf-1 kinase. PMID- 7799950 TI - Impaired cyclic AMP-dependent phosphorylation renders CREB a repressor of C/EBP induced transcription of the somatostatin gene in an insulinoma cell line. AB - Transcription factor CREB regulates cyclic AMP (cAMP)-dependent gene expression by binding to and activating transcription from cAMP response elements (CREs) in the promoters of target genes. The transcriptional transactivation functions of CREB are activated by its phosphorylation by cAMP-dependent protein kinase A (PKA). In studies of many different phenotypically distinct cells, the CRE of the somatostatin gene promoter is a prototype of a highly cAMP-responsive element regulated by CREB. We now report on a somatostatin-producing rat insulinoma cell line, RIN-1027-B2, in which transcription from the somatostatin gene promoter is paradoxically repressed by CREB. We find that CREB fails to transactivate a CRE containing somatostatin-chloramphenicol acetyltransferase reporter even when coexpressed with the catalytic subunit of PKA. CAAT box/enhancer-binding protein beta (C/EBP beta) and C/EBP-related activating transcription factor bind to the CRE in the promoter of the somatostatin gene and transactivate transcription. CREB binds competitively with C/EBP beta to the somatostatin CRE in vitro and represses C/EBP beta-induced transcription of the CRE-containing somatostatin chloramphenicol acetyltransferase reporter. The lack of CREB-mediated transcriptional stimulation is due to the presence of a heat-stable inhibitor of PKA that prevents activation of PKA and subsequent CREB phosphorylation in the nucleus. These findings indicate that dephosphorylated CREB is a negative regulator of C/EBP-activated transcription of the somatostatin gene promoter in RIN-1027-B2 cells. PMID- 7799951 TI - Spontaneous in vitro immortalization of breast epithelial cells from a patient with Li-Fraumeni syndrome. AB - Individuals with germ line mutations in the p53 gene, such as Li-Fraumeni syndrome (LFS), have an increased occurrence of many types of cancer, including an unusually high incidence of breast cancer. This report documents that normal breast epithelial cells obtained from a patient with LFS (with a mutation at codon 133 of the p53 gene) spontaneously immortalized in cell culture while the breast stromal fibroblasts from this same patient did not. Spontaneous immortalization of human cells in vitro is an extremely rare event. This is the first documented case of the spontaneous immortalization of breast epithelial cells from a patient with LFS in culture. LFS patient breast stromal fibroblasts infected with a retroviral vector containing human papillomavirus type 16 E7 alone were able to immortalize, whereas stromal cells obtained from patients with wild-type p53, similarly infected with human papillomavirus type 16 E7, did not. The present results indicate a protective role of normal pRb-like functions in breast stromal fibroblasts but not in breast epithelial cells and reinforces an important role of wild-type p53 in the regulation of the normal growth and development of breast epithelial tissue. PMID- 7799954 TI - Analysis of biological selections for high-efficiency gene targeting. AB - A two-marker selection system that allows the efficient isolation of diploid gene knockouts by two sequential rounds of targeted homologous recombination has been developed. A systematic evaluation of the biological parameters that govern the selection process showed that a successful strategy must match the expression level of the target gene, the efficacy of the marker, and the selection stringency. An enrichment ratio of 5,000- to 10,000-fold, which resulted in a 30% targeting efficiency of the c-myc gene in a fibroblast cell line, has been achieved. Such efficiency brings the difficulty of gene targeting effectively down to the level of simple transfections, since only 10 to 20 drug-resistant clones need to be screened to recover several homologous hits. The general utility of the targeting strategy is of interest to investigators studying gene function in a large variety of mammalian tissue culture systems. PMID- 7799953 TI - Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins. AB - Spliceosome assembly during pre-mRNA splicing requires the correct positioning of the U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) on the precursor mRNA. The structure and integrity of these snRNPs are maintained in part by the association of the snRNAs with core snRNP (Sm) proteins. The Sm proteins also play a pivotal role in metazoan snRNP biogenesis. We have characterized a Saccharomyces cerevisiae gene, SMD3, that encodes the core snRNP protein Smd3. The Smd3 protein is required for pre-mRNA splicing in vivo. Depletion of this protein from yeast cells affects the levels of U snRNAs and their cap modification, indicating that Smd3 is required for snRNP biogenesis. Smd3 is structurally and functionally distinct from the previously described yeast core polypeptide Smd1. Although Smd3 and Smd1 are both associated with the spliceosomal snRNPs, overexpression of one cannot compensate for the loss of the other. Thus, these two proteins have distinct functions. A pool of Smd3 exists in the yeast cytoplasm. This is consistent with the possibility that snRNP assembly in S. cerevisiae, as in metazoans, is initiated in the cytoplasm from a pool of RNA-free core snRNP protein complexes. PMID- 7799952 TI - The serum response factor nuclear localization signal: general implications for cyclic AMP-dependent protein kinase activity in control of nuclear translocation. AB - We have identified a basic sequence in the N-terminal region of the 67-kDa serum response factor (p67SRF or SRF) responsible for its nuclear localization. A peptide containing this nuclear localization signal (NLS) translocates rabbit immunoglobulin G (IgG) into the nucleus as efficiently as a peptide encoding the simian virus 40 NLS. This effect is abolished by substituting any two of the four basic residues in this NLS. Overexpression of a modified form of SRF in which these basic residues have been mutated confirms the absolute requirement for this sequence, and not the other basic amino acid sequences adjacent to it, in the nuclear localization of SRF. Since this NLS is in close proximity to potential phosphorylation sites for the cAMP-dependent protein kinase (A-kinase), we further investigated if A-kinase plays a role in the nuclear location of SRF. The nuclear transport of SRF proteins requires basal A-kinase activity, since inhibition of A-kinase by using either the specific inhibitory peptide PKIm or type II regulatory subunits (RII) completely prevents the nuclear localization of plasmid-expressed tagged SRF or an SRF-NLS-IgG conjugate. Direct phosphorylation of SRF by A-kinase can be discounted in this effect, since mutation of the putative phosphorylation sites in either the NLS peptide or the encoded full length SRF protein had no effect on nuclear transport of the mutants. Finally, in support of an implication of A-kinase-dependent phosphorylation in a more general mechanism affecting nuclear import, we show that the nuclear transport of a simian virus 40-NLS-conjugated IgG or purified cyclin A protein is also blocked by inhibition of A-kinase, even though neither contains any potential sites for phosphorylation by A-kinase or can be phosphorylated by A-kinase in vitro. PMID- 7799955 TI - Nucleolin is a matrix attachment region DNA-binding protein that specifically recognizes a region with high base-unpairing potential. AB - A DNA affinity column containing a synthetic double-stranded nuclear matrix attachment region (MAR) was used to purify a 100-kDa protein from human erythroleukemia K562 cells. This protein was identified as nucleolin, the key nucleolar protein of dividing cells, which is thought to control rRNA gene transcription and ribosome assembly. Nucleolin is known to bind RNA and single stranded DNA. We report here that nucleolin is also a MAR-binding protein. It binds double-stranded MARs from different species with high affinity. Nucleolin effectively distinguishes between a double-stranded wild-type synthetic MAR sequence with a high base-unpairing potential and its mutated version that has lost the unpairing capability but is still A+T rich. Thus, nucleolin is not merely an A+T-rich sequence-binding protein but specifically binds the base unpairing region of MARs. This binding specificity is similar to that of the previously cloned tissue-specific MAR-binding protein SATB1. Unlike SATB1, which binds only double-stranded MARs, nucleolin binds the single-stranded T-rich strand of the synthetic MAR probe approximately 45-fold more efficiently than its complementary A-rich strand, which has an affinity comparable to that of the double-stranded form of the MAR. In contrast to the high selectivity of binding to double-stranded MARs, nucleolin shows only a small but distinct sequence preference for the T-rich strand of the wild-type synthetic MAR over the T-rich strand of its mutated version. The affinity to the T-rich synthetic MAR is severalfold higher than to its corresponding RNA and human telomere DNA. Quantitative cellular fractionation and extraction experiments indicate that nucleolin is present both as a soluble protein and tightly bound to the matrix, similar to other known MAR-binding proteins. PMID- 7799957 TI - Identification of a ras-activated enhancer in the mouse osteopontin promoter and its interaction with a putative ETS-related transcription factor whose activity correlates with the metastatic potential of the cell. AB - The role of RAS in transducing signals from an activated receptor into altered gene expression is becoming clear, though some links in the chain are still missing. Cells possessing activated RAS express higher levels of osteopontin (OPN), an alpha v beta 3 integrin-binding secreted phosphoprotein implicated in a number of developmental, physiological, and pathological processes. We report that in T24 H-ras-transformed NIH 3T3 cells enhanced transcription contributes to the increased expression of OPN. Transient transfection studies, DNA-protein binding assays, and methylation protection experiments have identified a novel ras-activated enhancer, distinct from known ras response elements, that appears responsible for part of the increase in OPN transcription in cells with an activated RAS. In electrophoretic mobility shift assays, the protein-binding motif GGAGGCAGG was found to be essential for the formation of several complexes, one of which (complex A) was generated at elevated levels by cell lines that are metastatic. Southwestern blotting and UV light cross-linking studies indicated the presence of several proteins able to interact with this sequence. The proteins that form these complexes have molecular masses estimated at approximately 16, 28, 32, 45, 80, and 100 kDa. Because the approximately 16-kDa protein was responsible for complex A formation, we have designated it MATF for metastasis-associated transcription factor. The GGANNNAGG motif is also found in some other promoters, suggesting that they may be similarly controlled by MATF. PMID- 7799956 TI - Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages. AB - Mitogen-activated protein kinases (MAPKs) are activated upon a variety of extracellular stimuli in different cells. In macrophages, colony-stimulating factor 1 (CSF-1) stimulates proliferation, while bacterial lipopolysaccharide (LPS) inhibits cell growth and causes differentiation and activation. Both CSF-1 and LPS rapidly activate the MAPK network and induce the phosphorylation of two distinct ternary complex factors (TCFs), TCF/Elk and TCF/SAP. CSF-1, but not LPS, stimulated the formation of p21ras. GTP complexes. Expression of a dominant negative ras mutant reduced, but did not abolish, CSF-1-mediated stimulation of MEK and MAPK. In contrast, activation of the MEK kinase Raf-1 was Ras independent. Treatment with the phosphatidylcholine-specific phospholipase C inhibitor D609 suppressed LPS-mediated, but not CSF-1-mediated, activation of Raf 1, MEK, and MAPK. Similarly, down-regulation or inhibition of protein kinase C blocked MEK and MAPK induction by LPS but not that by CSF-1. Phorbol 12-myristate 13-acetate pretreatment led to the sustained activation of the Raf-1 kinase but not that of MEK and MAPK. Thus, activated Raf-1 alone does not support MEK/MAPK activation in macrophages. Phosphorylation of TCF/Elk but not that of TCF/SAP was blocked by all treatments that interfered with MAPK activation, implying that TCF/SAP was targeted by a MAPK-independent pathway. Therefore, CSF-1 and LPS target the MAPK network by two alternative pathways, both of which induce Raf-1 activation. The mitogenic pathway depends on Ras activity, while the differentiation signal relies on protein kinase C and phosphatidylcholine specific phospholipase C activation. PMID- 7799958 TI - Lack of an effect of the efficiency of RNA 3'-end formation on the efficiency of removal of either the final or the penultimate intron in intact cells. AB - Evidence exists from studies using intact cells that intron removal can be influenced by the reactivity of upstream and downstream splice sites and that cleavage and polyadenylation can be influenced by the reactivity of upstream splice sites. These results indicate that sequences within 3'-terminal introns can function in the removal of upstream introns as well as the formation of RNA 3' ends. Evidence from studies using intact cells for an influence of RNA 3'-end formation on intron removal is lacking. We report here that mutations within polyadenylation sequences that either decrease or increase the efficiency of RNA 3'-end formation have no effect on the efficiencies with which either the 3' terminal or the penultimate intron is removed by splicing. Northern (RNA) blot hybridization, RNase mapping, and an assay that couples reverse transcription and PCR were used to analyze the effects of deletions and a substitution of the polyadenylation sequences within the human gene for triosephosphate isomerase (TPI). TPI pre-mRNA harbors six introns that are constitutively removed by splicing. Relative to normal levels, each of the deletions was found to reduce the nuclear and cytoplasmic levels of TPI mRNA, increase the nuclear level of unprocessed RNA 3' ends, and decrease the nuclear level of processed RNA 3' ends. The simplest interpretation of these data indicates that (i) the rate of 3'-end formation normally limits the amount of mRNA produced and (ii) the deletions decrease and the substitution increases the efficiency of RNA 3'-end formation. While each of the deletions and the substitution altered the absolute levels of intron 6-containing, intron 5-containing, intron 6-free, and intron 5-free RNAs, in no case was there an abnormal ratio of intron-containing to intron-free RNA for either intron. Therefore, at least for TPI RNA, while the efficiency of removal of the 3'-terminal intron influences the efficiency of removal of either the 3'-end formation, the efficiency of RNA 3'-end formation does not influence the efficiency of removal of either the 3'-terminal or penultimate intron. The dependence of TPI RNA 3'-end formation on splicing may reflect the suboptimal strengths of the corresponding regulatory sequences and may function to ensure that TPI pre-mRNA is not released from the chromatin template until it has formed a complex with spliceosomes. If so, then the independence of TPI RNA splicing on 3'-end formation may be rationalized by the lack of a comparable function. PMID- 7799959 TI - Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. AB - Phosphorylation of heat shock protein 27 (HSP27) can modulate actin filament dynamics in response to growth factors. During heat shock, HSP27 is phosphorylated at the same sites and by the same protein kinase as during mitogenic stimulation. This suggests that the same function of the protein may be activated during growth factor stimulation and the stress response. To determine the role of HSP27 phosphorylation in the heat shock response, several stable Chinese hamster cell lines that constitutively express various levels of the wild type HSP27 (HU27 cells) or a nonphosphorylatable form of human HSP27 (HU27pm3 cells) were developed. In contrast to HU27 cells, which showed increased survival after heat shock, HU27pm3 cells showed only slightly enhanced survival. Evidence is presented that stabilization of microfilaments is a major target of the protective function of HSP27. In the HU27pm3 cells, the microfilaments were thermosensitized compared with those in the control cells, whereas wild-type HSP27 caused an increased stability of these structures in HU27 cells. HU27 but not HU27pm3 cells were highly resistant to cytochalasin D treatment compared with control cells. Moreover, in cells treated with cytochalasin D, wild-type HSP27 but not the phosphorylated form of HSP27 accelerated the reappearance of actin filaments. The mutations in human HSP27 had no effect on heat shock-induced change in solubility and cellular localization of the protein, indicating that phosphorylation was not involved in these processes. However, induction of HSP27 phosphorylation by stressing agents or mitogens caused a reduction in the multimeric size of the wild-type protein, an effect which was not observed with the mutant protein. We propose that early during stress, phosphorylation-induced conformational changes in the HSP27 oligomers regulate the activity of the protein at the level of microfilament dynamics, resulting in both enhanced stability and accelerated recovery of the filaments. The level of protection provided by HSP27 during heat shock may thus represent the contribution of better maintenance of actin filament integrity to overall cell survival. PMID- 7799960 TI - A silencer element for the lipoprotein lipase gene promoter and cognate double- and single-stranded DNA-binding proteins. AB - Transfection experiments with constructs containing various 5'-deleted fragments of the human lipoprotein lipase (LPL) promoter and the chloramphenicol acetyltransferase reporter gene revealed an LPL silencer element (LSE) in the region of nucleotides -225 to -81 of the LPL gene that functioned in Chinese hamster ovary (CHO) and HeLa cells. Gel retardation competition analysis showed the presence of a nuclear factor(s) capable of binding to the sequence of nucleotides -169 to -152 of LSE (LSE-6) in a single-stranded (opposite-strand) and double-stranded specific fashion, the binding affinity being almost the same in the two binding forms. Site-directed mutagenesis indicated that almost the entire sequence of LSE-6 was necessary to form the complexes and also critical for silencing activity in CHO cells. The amounts of this binding factor(s) in CHO and HeLa cells were closely associated with transcriptional silencing activity. Photochemical cross-linking experiments indicated that the single- and double stranded elements recognized the same binding factor(s) with molecular masses of 54 to 63 kDa and 109 to 124 kDa. The 109- to 124-kDa DNA binding factor(s) was found to be a doublet of that of the 54- to 63-kDa factor by isoelectric focusing or by increasing the time of exposure to UV irradiation. When inserted upstream of another gene such as that of the simian virus 40 enhancer/promoter of pSV2CAT, the sequence of nucleotides -190 to -143 (LSE-1) also suppressed transcription of the reporter gene in CHO cells. These results strongly suggest that the LSE plays a role in regulation of LPL gene expression by suppressing its transcription. PMID- 7799962 TI - Transcriptional activation by the parvoviral nonstructural protein NS-1 is mediated via a direct interaction with Sp1. AB - The nonstructural protein NS-1, encoded by the parvovirus minute virus of mice, is a potent regulator of viral gene expression. NS-1 does not bind DNA in a sequence-specific manner, and the mechanism by which it modulates viral promoter function is unclear. We have used Gal4-NS-1 fusion protein constructs to identify and characterize an activating domain encoded within the C-terminal 88 amino acids of NS-1 which competes effectively with the acidic activator domain of the herpes simplex virus VP16 protein. DNA affinity chromatography and immunoprecipitation experiments demonstrate that protein-protein interactions between the transcription factor Sp1 and NS-1 are required to bind NS-1 to promoter DNA in vitro. Cotransfection of Gal4-NS-1 and Sp1-VP16 acidic activator constructs into Drosophila melanogaster Schneider cells, which lack endogenous Sp1, stimulates transcription from a minimal promoter containing five Gal4 binding sites, while single-construct transfections do not. Cotransfection of Schneider cells with wild-type NS-1 and Sp1 constructs activates transcription from a simian virus 40 promoter 10- to 30-fold over that of either construct alone. Thus, Sp1-NS-1 interactions in vivo can stimulate transcription from a heterologous promoter containing Sp1 binding sites. PMID- 7799961 TI - The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation. AB - The Leu3 protein of Saccharomyces cerevisiae has been shown to be a transcriptional regulator of genes encoding enzymes of the branched-chain amino acid biosynthetic pathways. Leu3 binds to upstream activating sequences (UASLEU) found in the promoters of LEU1, LEU2, LEU4, ILV2, and ILV5. In vivo and in vitro studies have shown that activation by Leu3 requires the presence of alpha isopropylmalate. In at least one case (LEU2), Leu3 actually represses basal-level transcription when alpha-isopropylmalate is absent. Following identification of a UASLEU-homologous sequence in the promoter of GDH1, the gene encoding NADP(+) dependent glutamate dehydrogenase, we demonstrate that Leu3 specifically interacts with this UASLEU element. We then show that Leu3 is required for full activation of the GDH1 gene. First, the expression of a GDH1-lacZ fusion gene is three- to sixfold lower in a strain lacking the LEU3 gene than in an isogenic LEU3+ strain. Expression is restored to near-normal levels when the leu3 deletion cells are transformed with a LEU3-bearing plasmid. Second, a significant decrease in GDH1-lacZ expression is also seen when the UASLEU of the GDH1-lacZ construct is made nonfunctional by mutation. Third, the steady-state level of GDH1 mRNA decreases about threefold in leu3 null cells. The decrease in GDH1 expression in leu3 null cells is reflected in a diminished specific activity of NADP(+) dependent glutamate dehydrogenase. We also demonstrate that the level of GDH1 lacZ expression correlates with the cells' ability to generate alpha isopropylmalate and is lowest in cells unable to produce alpha-isopropylmalate. We conclude that GDH1, which plays an important role in the assimilation of ammonia in yeast cells, is, in part, activated by a Leu3-alpha-isopropylmalate complex. This conclusion suggests that Leu3 participates in transcriptional regulation beyond the branched-chain amino acid biosynthetic pathways. PMID- 7799963 TI - The yeast TATA-binding protein (TBP) core domain assembles with human TBP associated factors into a functional TFIID complex. AB - In mammalian and Drosophila cells, the central RNA polymerase II general transcription factor TFIID is a multisubunit complex containing the TATA-binding protein (TBP) and TBP-associated factors (TAFs) bound to the conserved TBP carboxy-terminal core domain. TBP also associates with alternative TAFs in these cells to form general transcription factors required for initiation by RNA polymerases I and III. Although extracts of human HeLa cells contain little TBP that is not associated with TAFs, free TBP is readily isolated from yeast cell extracts. However, recent studies indicate that yeast TBP can also interact with other yeast polypeptides to form multiprotein complexes. We established stable human HeLa cell lines expressing yeast TBP and several yeast-human TBP hybrids to study TBP-TAF interactions. We found that the yeast TBP core domain assembles with a complete set of human TAFs into a stable TFIID complex that can support activated transcription in vitro. The fact that the yeast TBP core, which differs from human TBP core in approximately 20% of its amino acid residues, has the structural features required to form a stable complex with human TAFs implies that Saccharomyces cerevisiae probably contains TAFs that are structurally and functionally analogous to human TAFs. Surprisingly, the non-conserved amino terminus of yeast TBP inhibited association between the yeast core domain and human TAFs. PMID- 7799964 TI - Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase activating domain that affects cell cycle progression. AB - We have cloned a novel cDNA (Spa-1) which is little expressed in the quiescent state but induced in the interleukin 2-stimulated cycling state of an interleukin 2-responsive murine lymphoid cell line by differential hybridization. Spa-1 mRNA (3.5 kb) was induced in normal lymphocytes following various types of mitogenic stimulation. In normal organs it is preferentially expressed in both fetal and adult lymphohematopoietic tissues. A Spa-1-encoded protein of 68 kDa is localized mostly in the nucleus. Its N-terminal domain is highly homologous to a human Rap1 GTPase-activating protein (GAP), and a fusion protein of this domain (SpanN) indeed exhibited GAP activity for Rap1/Rsr1 but not for Ras or Rho in vitro. Unlike the human Rap1 GAP, however, SpanN also exhibited GAP activity for Ran, so far the only known Ras-related GTPase in the nucleus. In the presence of serum, stable Spa-1 cDNA transfectants of NIH 3T3 cells (NIH/Spa-1) hardly overexpressed Spa-1 (p68), and they grew as normally as did the parental cells. When NIH/Spa-1 cells were serum starved to be arrested in the G1/G0 phase of the cell cycle, however, they, unlike the control cells, exhibited progressive Spa-1 p68 accumulation, and following the addition of serum they showed cell death resembling mitotic catastrophes of the S phase during cell cycle progression. The results indicate that the novel nuclear protein Spa-1, with a potentially active Ran GAP domain, severely hampers the mitogen-induced cell cycle progression when abnormally and/or prematurely expressed. Functions of the Spa-1 protein and its regulation are discussed in the context of its possible interaction with the Ran/RCC-1 system, which is involved in the coordinated nuclear functions, including cell division. PMID- 7799966 TI - The bulk chromatin structure of a murine transgene does not vary with its transcriptional or DNA methylation status. AB - The DNA methylation status of HRD, a murine transgene, can be controlled by the genetic background upon which it is carried. We found the transgene to be transcribed in competent tissues only when undermethylated. Chromatin structure over the transgene was assayed by nuclear accessibility with DNase I, MspI, and PstI. While the transgene was up to fivefold more resistant to MspI when methylated than when not methylated, we observed no such difference with DNase I or PstI. We suggest that methyl-CpG-binding proteins are responsible for the difference observed with MspI, but that the chromatin structures are otherwise similarly compacted. Methylation could, therefore, play a regulatory role in gene expression beyond that which can be accomplished by bulk chromatin structure alone. PMID- 7799965 TI - Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene. AB - The transcript for the high-affinity Ca2+/calmodulin-binding protein calspermin is generated from the gene encoding Ca2+/calmodulin-dependent protein kinase IV only in postmeiotic germ cells during spermatogenesis. We demonstrate that this testis-specific calspermin transcript can be produced in heterologous cells by utilization of a promoter located in an intron of the calmodulin (CaM) kinase IV gene. Critical motifs within this promoter are two cyclic AMP response element (CRE)-like sequences located about -70 and -50 bp upstream of the transcriptional initiation site. Both CRE motifs are footprinted by the authentic testis-specific transcriptional activator CREM tau or by CREM tau present in adult testis nuclear extract. Whereas a 2.1-kb DNA fragment containing the calspermin promoter is inactive when transfected into NIH 3T3 cells, activity can be restored by cotransfection of CREM tau and protein kinase A or CaM kinase IV but not CaM kinase II alpha. Restoration of activity is greatly reduced by mutation of the two CRE motifs. Since CRE-like motifs have been identified in many genes uniquely expressed in postmeiotic germ cells, which contain abundant CREM tau protein, we suggest that CREM tau may function as one transcription factor responsible for the expression of postmeiotic germ cell-specific genes. PMID- 7799967 TI - Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi 1/PU.1. AB - Interleukin-1 beta (IL-1 beta) is produced primarily by stimulated monocytes, suggesting that the IL1B gene, which codes for this protein, depends upon at least one cell-type-specific factor. Our previous characterization of the IL1B promoter indicated that the region between -131 and +12 is sufficient to direct cell-type-specific expression of a reporter gene (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M.J. Fenton, A.C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). We now show that a sequence located between positions -50 and -39 of the IL1B promoter binds the tissue-restricted Ets domain transcription factor Spi-1/PU.1 (Spi-1). Mutation of this site abrogates binding of this factor and reduces the ability of the IL1B promoter to function in macrophages. A second Spi-1 binding site located between positions -115 and -97 also is required for maximal IL1B promoter activity in the presence of the proximal Spi-1 binding site. In addition, an activation domain-deficient Spi-1 expression vector acts as a dominant-negative inhibitor of reporter gene expression in a monocyte cell line. Finally, the IL1B promoter, which is inactive in Spi-1-deficient HeLa cells, is activated in these cells by cotransfection with a Spi-1 expression vector. Thus, the cell-type-specific expression of the IL1B promoter appears to be dependent on the binding of Spi-1. PMID- 7799968 TI - Selective expression of intracisternal A-particle genes in established mouse plasmacytomas. PMID- 7799969 TI - Notice of duplicate publication. Molecular genetic analyses of a 376-kilodalton Golgi complex membrane protein (giantin) PMID- 7799970 TI - Isoform-specific complementation of the yeast sac6 null mutation by human fimbrin. AB - The actin cytoskeleton is a fundamental component of eukaryotic cells, with both structural and motile roles. Actin and many of the actin-binding proteins found in different cell types are highly conserved, showing considerable similarity in both primary structure and biochemical properties. To make detailed comparisons between homologous proteins, it is necessary to know whether the various proteins are functionally, as well as structurally, conserved. Fimbrin is an example of a cytoskeletal component that, as shown by sequence determinations and biochemical characterizations, is conserved between organisms as diverse as Saccharomyces cerevisiae and humans. In this study, we examined whether the human homolog can substitute for the yeast protein in vivo. We report here that two isoforms of human fimbrin, also referred to as T- and L-plastin, can both substitute in vivo for yeast fimbrin, also known as Sac6p, whereas a third isoform, I-fimbrin (or I plastin), cannot. We demonstrate that the human T- and L-fimbrins, in addition to complementing the temperature-sensitive growth defect of the sac6 null mutant, restore both normal cytoskeletal organization and cell shape to the mutant cells. In addition, we show that human T- and L-fimbrins can complement a sporulation defect caused by the sac6 null mutation. These findings indicate that there is a high degree of functional conservation in the cytoskeleton, even between organisms as diverse as S. cerevisiae and humans. PMID- 7799972 TI - A selector of transcription initiation in the protozoan parasite Toxoplasma gondii. AB - The recent development of an efficient transfection system for the apicomplexan Toxoplasma gondii allows a comprehensive dissection of the elements involved in gene transcription in this obligate intracellular parasite. We demonstrate here that for the SAG1 gene, a stretch of six repeated sequences in the region 35 to 190 bp upstream of the first of two transcription start sites is essential for efficient and accurate transcription initiation. This repeat element shows characteristics of a selector in determining the position of the transcription start sites. PMID- 7799971 TI - The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing. AB - The C terminus of nuclear hormone receptors is a complex structure that contains multiple functions. We are interested in the mechanism by which thyroid hormone converts its receptor from a transcriptional silencer to an activator of transcription. Both regulatory functions are localized in the ligand binding domain of this receptor superfamily member. In this study, we have identified and characterized several functional domains within the ligand binding domain of the human thyroid hormone receptor (TR beta) conferring transactivation. Interestingly, these domains are localized adjacent to hormone binding sites. One activation domain, designated tau 4, is only 17 amino acids in length and is localized at the extreme C terminus of TR. Deletion of six amino acids of tau 4 resulted in a receptor that could still bind hormone but acted as a constitutive silencer, indicating that tau 4 is required for both transactivation and relief of the silencing functions. In addition, we performed in vivo competition experiments, the results of which suggest that in the absence of tau 4 or hormone, TR is bound by a corepressor protein(s) and that one role of hormone is to release corepressor from the receptor. We propose a general model in which the role of hormone is to induce a conformational change in the receptor that subsequently affects the action of tau 4, leading to both relief of silencing and transcriptional activation. PMID- 7799974 TI - Management strategies for congenital infections. AB - Information on congenital infection is continuously expanding. New diagnostic techniques are making significant contributions to the prenatal diagnosis of several fetal infections. In this review we highlight some of the most recent advances in the diagnosis and management of the most common fetal infections, those caused by cytomegalovirus, human immunodeficiency virus 1, Toxoplasma, varicella-zoster virus, and parvovirus B19. PMID- 7799976 TI - Multifetal pregnancy: risks and methods of reduction. AB - Multifetal pregnancy reduction offers an acceptable option to patients faced with the significant risk of long-term morbidity associated with multifetal gestation, especially gestation involving 4 or more fetuses. Until advances in reproductive technology eliminate the iatrogenic occurrence of multifetal gestation, and until progress in perinatal care decreases the threat of preterm delivery, multifetal pregnancy reduction offers hope for a good outcome in an otherwise dismal situation. PMID- 7799975 TI - Platelet disorders in pregnancy: implications for mother and fetus. AB - Platelet disorders in pregnancy are not uncommon. Most often, obstetricians are faced with a patient with undiagnosed thrombocytopenia and have the responsibility of deciding if the condition is ITP, gestational thrombocytopenia, or a process related to pre-eclampsia. Correct diagnosis is important because ITP can be associated with fetal thrombocytopenia, making route of delivery important. In alloimmune thrombocytopenia, the mother develops antibodies to a specific platelet antigen present on the fetal platelet but absent on her own. Severe AIT can cause intracranial hemorrhage and have disastrous consequences for the fetus and neonate. In preliminary studies antenatal intravenous gamma globulin therapy has shown promise in preventing the development of intracranial hemorrhage and ameliorating fetal thrombocytopenia. Essential thrombocythemia with a platelet count of greater than 600 x 10(9) platelet/L can occur in pregnancy; therapy consists of antiplatelet aggregating agents such as aspirin, and plateletpheresis. Platelet function disorders can be acquired or inherited. Acquired platelet dysfunction disorders are usually caused by drugs such as aspirin or indomethacin, or by a systemic disease. Hereditary disorders of platelet function can be diagnosed in utero, but cordocentesis may represent an unacceptably high risk. For prenatal diagnosis, other methods, such as chorionic villus sampling or amniocentesis, should be investigated as an alternative to the potentially high risk of cordocentesis. PMID- 7799973 TI - The BN51 protein is a polymerase (Pol)-specific subunit of RNA Pol III which reveals a link between Pol III transcription and pre-rRNA processing. AB - The three eukaryotic nuclear RNA polymerase (Pol) contain common and unique subunits. Cloning of the unique Pol III subunit genes in yeast cells has revealed a potential homolog in the mammalian system, the BN51 gene. The human BN51 gene was originally isolated as a suppressor of a temperature-sensitive cell cycle mutant of BHK cells (tsBN51). Although tsBN51 cells have a marked decrease in RNA Pol III activity at the nonpermissive temperature, direct biochemical evidence for the BN51 protein being a human Pol III subunit was lacking. Using antibodies directed against the BN51 protein, we show the following: (i) the BN51 protein copurifies with Pol III activity, (ii) Pol III activity can be specifically immunoprecipitated from HeLa nuclear extracts, and (iii) the immunopurified BN51 complex is active in restoring both nonspecific and promoter-specific Pol III activity. Our findings provide direct biochemical evidence for BN51 being a Pol III-specific subunit. Despite the fact that BN51 is not a subunit of Pol I, the production of mature Pol I transcripts is inhibited in tsBN51 cells at the nonpermissive temperature. tsBN51 cells appear defective in processing the 32S precursor rRNA into mature 5.8S and 28S rRNA at the nonpermissive temperature. We surmise that ribosome assembly has halted because of the loss of Pol III transcripts. Thus, there is regulation of the synthesis of mature Pol I transcripts by a posttranscriptional mechanism based on the availability of Pol III transcripts. PMID- 7799977 TI - Development of the ability to make IgG and IgA in newborns and infants. AB - An understanding of the ontogeny of the human immune system may provide clues for methods to stimulate the immune response of neonates and young infants at an earlier age than is now possible. Knowledge of normal changes in immune response over time is necessary to evaluate infants for immunodeficiency. PMID- 7799978 TI - The lung of the premature infant: pathophysiology of disease and newer therapies. PMID- 7799979 TI - New perspectives on neonatal hyperbilirubinemia. AB - Notwithstanding a number of advances in the understanding of hyperbilirubinemia and its treatment in the newborn, controversy continues. The trend has been to decrease interventions and observe and manage infants with jaundice as outpatients. This trend will probably prove to be both medically and economically sound. In the absence of significant hemolysis or other underlying medical conditions such as infection, many physicians are now comfortable with expectant observation for those healthy full-term infants with serum bilirubin measurements of less than 18 mg/dL. New thinking about this condition and advances in treatment may transform hyperbilirubinemia in neonates into a medical curiosity. PMID- 7799981 TI - Influence of baclofen upon the alpha-motoneuron in spasticity by means of F-wave analysis. AB - Intrathecal baclofen dramatically improves severe spastic syndromes. This improvement is likely related to reduced excitability of alpha-motoneurons. To investigate the influence of baclofen upon the alpha-motoneuron, we analyzed F waves before and after intrathecal baclofen bolus injection (usually 50 micrograms) as well as after administration of different, constantly delivered doses (60-200 micrograms/day). Intrathecal baclofen bolus decreased the maximum F wave amplitude (Fp) from an initial value of 9% of the maximum M amplitude (Mmax) (= F/M-ratio) to 2.4% of the Mmax after 130-180 min, reduced the mean F-wave amplitude 60% within 150 min, and shortened the mean duration by 40-60% after 130 180 min. Constantly delivered baclofen of 100 micrograms/day reduced the F/M ratio from 5% to 2%, the mean F-wave amplitude by 40-80%, and the F-wave mean duration by 40-80%. The minimum F-wave latency did not change after bolus or during steady state administration. The findings indicate that the F-wave mean and maximum amplitude as well as the mean duration are altered in a quantifiable manner following intrathecal baclofen application. PMID- 7799980 TI - Spontaneous chromosomal aberrations in Fanconi anaemia, ataxia telangiectasia fibroblast and Bloom's syndrome lymphoblastoid cell lines as detected by conventional cytogenetic analysis and fluorescence in situ hybridisation (FISH) technique. AB - Several primary and transformed human cell lines derived from cancer prone patients are employed routinely for biochemical and DNA repair studies. Since transformation leads to some chromosomal instability a cytogenetic analysis of spontaneous chromosome aberrations in fibroblast cell lines derived from patients with Fanconi anaemia (FA), ataxia telangiectasia (AT), and in lymphoblastoid cell lines derived from patients with Bloom's syndrome (BS), was undertaken. Unstable aberrations were analysed in Giemsa stained preparations and the chromosome painting technique was used for evaluating the frequencies of stable aberrations (translocations). In addition, the frequency of sister-chromatid exchanges (SCEs) was determined in differentially stained metaphases. The SV40-transformed fibroblasts from these cell lines have higher frequencies of unstable aberrations than the primary fibroblasts. In the four lymphoblastoid cell lines derived from BS patients higher frequencies of spontaneously occurring chromosomal aberrations in comparison to normal TK6wt cells were also evident. The frequency of spontaneously occurring chromosome translocations was determined with fluorescence in situ hybridisation (FISH) and using DNA libraries specific for chromosomes 1, 2, 3, 4, 7, 8, 11, 14, 19, 20 and X. The translocation levels were found to be elevated for primary FA fibroblasts and lymphoblastoid cells derived from BS patients in comparison with control cell lines, hetero- and homozygote BS cell lines not differing in this respect. The SV40-transformed cell lines showed very high frequencies of translocations independent of their origin and almost every cell contained at least one translocation. In addition, clonal translocations were found in transformed control TK6wt and AT cell lines for chromosomes 20 and 14, respectively. The spontaneous frequencies of SCEs were similar in transformed fibroblasts derived from normal individuals and AT patients, whereas in SV40-transformed FA cells these were higher (4-fold). Among cell lines derived from BS patients, heterozygote lines behaved like control, whereas in homozygote cell lines very high frequencies of SCEs (about 12-fold) were evident. PMID- 7799982 TI - Selective finger drop in cervical radiculopathy: the pseudopseudoulnar claw hand. PMID- 7799983 TI - Amyotrophic lateral sclerosis associated with isolated adrenocorticotrophic hormone deficiency. PMID- 7799984 TI - Scalp-recorded P14 in median nerve SEPs is abolished by cuneate nucleus lesion. PMID- 7799985 TI - The effect of wrist size on the orthodromic median sensory nerve action potential. PMID- 7799986 TI - Riche-Cannieu anastomosis with partial transection of the median nerve. PMID- 7799987 TI - Chloroquine treated rat: a possible model for Alzheimer's disease. PMID- 7799988 TI - Dorsal rhizotomy for cerebral palsy. PMID- 7799989 TI - Deficits in the function of small and large afferent fibers in confirmed cases of CTS. PMID- 7799990 TI - Intrapontine generation of mykomia in multiple sclerosis. PMID- 7799991 TI - A retrospective study of 47 patients with highly elevated anti-GM1 antibodies. PMID- 7799992 TI - Diabetic muscle infarction: magnetic resonance imaging (MRI) avoids the need for biopsy. PMID- 7799994 TI - Sixth Annual Stuart Reiner Memorial Lecture: embryonic development of nerve and muscle. AB - This article provides a basic scheme of sequential anatomic and some physiologic events occurring during the course of embryonic development of motor neurons and muscles, leading to the establishment of mature nerve-muscle relationships. Motor neurons and muscles begin their development independently and during embryogenesis they become dependent on each other for further development and survival. Aspects of development which occur independently and those requiring mutual interactions are identified. The development of motor neurons is discussed with respect to their production, projection, neuromuscular transmission, myelination, sprouting, survival, and death. The development of muscles is discussed with respect to the origin, differentiation, and muscle fiber types. Discussion on the development of neuromuscular junction includes differentiation of presynaptic nerve terminal, postsynaptic components, and elimination of multiple axons. PMID- 7799993 TI - Efficacy of obidoxime in human organophosphorus poisoning: determination by neuromuscular transmission studies. AB - Six patients with organophosphorus compound intoxications developed an intermediate syndrome (weakness and fasciculations) and obidoxime was given on eight occasions. The efficacy of the acetylcholinesterase (AChE) reactivator was monitored electrophysiologically by neuromuscular transmission studies using single and repetitive nerve stimulation (20 and 50 Hz) and the activity of the serum (butyryl) cholinesterase (ChE). Dramatic electrophysiologic improvement was seen when obidoxime was given early within 12 h in 3 patients, although evidence of AChE inhibition did not subside completely. When administration of obidoxime was delayed 26 h or more after intoxication on five occasions, electrophysiologic improvement was mild or absent. In one case, 66 h after intoxication with oxydemeton-S-methyl, the neuromuscular block worsened, indicating that aging of the AChE had been completed. The electrophysiologic improvement was always accompanied with better motor function but not necessarily with improvement of the overall clinical status. Serum ChE did not predict the oxime effect at the motor endplate. In humans, the efficacy of oximes in AChE reactivation can be determined rapidly using electrophysiologic studies. PMID- 7799995 TI - Expression of heat-shock/stress proteins in Duchenne muscular dystrophy. AB - Heat-shock/stress proteins (HSPs) are induced in response to stressful conditions and are essential for survival during and after cellular stress. We investigated whether dystrophin deficiency in muscle from Duchenne muscular dystrophy (DMD) patients induces HSPs. Immunohistochemical studies were performed on cryosections from normal muscle, heat-shocked muscle, and muscle from patients with DMD, dermatomyositis, and mitochondrial myopathy using antibodies against HSP 72/73, HSP 72, HSP 90, groEL (HSP 65 homologue), and ubiquitin. Computer-assisted image processing revealed a significant (P < 0.05) induction of HSP 72/73, 72, 65, and ubiquitin in hypercontracted fibers; HSP 90 and ubiquitin in regenerating fibers; and ubiquitin in macrophage invaded necrotic fibers of DMD muscle. No significant induction of HSPs was observed in dermatomyositis or mitochondrial myopathies. The stress response induced in DMD may relate to the metabolic stress characteristic of the disease and could represent an autoprotective mechanism. Manipulation of this protective response may reduce injury and have potential therapeutic application. PMID- 7799996 TI - The medial calcaneal nerve: anatomy and nerve conduction technique. AB - We report a new technique for studying conduction in the medial calcaneal nerve (MCN). Dissection of 14 cadaver feet revealed the optimal G1 site to be one third of the way from the apex of the heel to a point midway between the navicular tuberosity and the prominence of the medial malleolus. Seventy-two feet (36 healthy volunteers) were studied using surface stimulation of the tibial nerve 10 cm proximal to the G1 surface electrode. Averaging technique was not required. Reference values (mean +/- 2 SD) were determined for MCN onset latency (2.0 +/- 0.3 ms), peak latency (2.5 +/- 0.3 ms), onset conduction velocity (61 +/- 11 m/s), peak conduction velocity (40 +/- 5 m/s), baseline-to-peak amplitude (18 +/- 6 microV), and maximum intrasubject side-to-side differences in these values (0.3 ms, 0.3 ms, 15 m/s, 5 m/s, and 17 microV, respectively). This study provides an easily performed, reproducible method for electrophysiologic evaluation of the MCN. PMID- 7799997 TI - Lymphocyte infiltration following allo- and xenomyoblast transplantation in mdx mice. AB - Human and mouse (C57BL/10SnJ+/+) myoblasts were injected separately in the muscles of C57BL/10ScSn mdx/mdx mice. Mouse myoblasts (C57BL/10SnJ+/+) were also injected in normal mice (C57BL/10SnJ+/+ and BALB/c+/+). Some muscles that received a xenotransplantation (i.e., human myoblasts) were previously injected with a myotoxin, i.e., notexin. This treatment was not used for the allografts (i.e., mouse myoblasts). Human myoblast injections did not increase the number of dystrophin-positive cells above the background level due to backmutation. Moreover, the human myoblasts detected with an anti-HLA antibody decreased rapidly during the 6-week follow-up. The injection of normal mouse myoblasts in mdx mice did, however, increase the number of dystrophin-positive fibers. Moreover, numerous cells expressing mouse MHC class II, macrophages, granulocytes, neutrophils, natural killer cells, and a subset of T lymphocytes were detected by immunohistochemistry in cryostat sections of myoblast-injected muscles. These cells were present within 1 week of the myoblast injection in the muscle regions containing injected human or mouse myoblasts, and progressively decreased during the 6-week follow-up in the human myoblast transplantation. Lymphocyte infiltration reached a significant level following xeno- and alloincompatible transplantations. Antibodies against the human myoblasts and against alloincompatible myoblasts were also detected in the serum of the recipients. These results suggest that humoral and cellular immune reactions are responsible for the poor outcome of myoblast transplantation in mice and could be involved in failure of transplantation in Duchenne muscular dystrophy patients. These results indicate that adequate immunosuppression must be used in these patients. PMID- 7799998 TI - Extensor digitorum brevis reflex in normals and patients with radiculopathies. AB - This prospective study evaluated the extensor digitorum brevis deep tendon reflex (EDBR) in a normal population and in patients with L-5 and S-1 radiculopathies. There were 88 subjects: 53 normals, 17 L-5, and 18 S-1 radiculopathy subjects. The clinical EDBR revealed a 91% specificity, with 18% sensitivity for L-5, and 11% for S-1. The electrodiagnostic EDBR yielded increased sensitivities of 35% for L-5 (P = 0.07) and 39% for S-1 (P = 0.04), with 87% specificity. H-reflexes showed 50% sensitivity for the S-1 group (P = 0.0006) and 91% specificity. EDBR latencies were significantly related to age and leg length (r2 = 0.46, P < 0.0001). Age alone explained 26% (P < 0.0001) of the EDBR variability and leg length 20% (P < 0.0001). EDBR clinical and electrodiagnostic reflexes have low sensitivities, high specificities, and do not discriminate L-5 from S-1 root involvement. PMID- 7799999 TI - Factors which influence alterations of phosphates and pH in exercising human skeletal muscle: measurement error, reproducibility, and effects of fasting, carbohydrate loading, and metabolic acidosis. AB - Previous studies have shown considerable variability in the metabolic response of human skeletal muscle during a standardized exercise protocol. The goal of these studies was to investigate the factors responsible for the broad range of metabolic changes produced by fatiguing exercise. Experiments were performed to quantitate the measurement error of 31P nuclear magnetic resonance spectroscopy of human muscle, the reproducibility of changes within a single subject, and the effects of fasting, carbohydrate loading, and metabolic acidosis. The results show that none of these factors appear to be responsible for the wide variation between subjects. However, the effects of training and genetic factors were not investigated and are likely to be responsible for the substantial variability between subjects. PMID- 7800000 TI - CMAP variability as a function of electrode site and size. AB - The site of the recording electrode influences the amplitude of the compound muscle action potential (CMAP) and its variation over a length of nerve. The effects of large electrodes on this source of intraindividual variability were assessed. Right median nerves of 20 healthy subjects were studied, and recordings made at three sites (at 1-cm intervals) using five electrode sizes (0.01, 1, 2, 4, and 10 cm2). Site-induced variability was defined as the standard deviation (SDi) and coefficient of variation (CVi) of the measurements of the three sites. Site induced variability of all parameters (latency, duration, amplitude, area, MNCV, and the percentile changes of duration, amplitude, and area over the forearm) decreased significantly with electrode size. Decreases were most pronounced for amplitude and area: CVi fell from 29% and 30% (0.01-cm2 electrode) to 10% and 8% (10 cm2). It is argued that large electrodes record activity of more motor units than small electrodes, and that their measurement fields overlap to a greater extent. The use of large electrodes is recommended in order to reduce site-induced CMAP variability. PMID- 7800001 TI - Transfer function analysis of respiratory sinus arrhythmia: a measure of autonomic function in diabetic neuropathy. AB - Standard techniques measuring heart rate (HR) variability do not account for its dependence on the rate and depth of respiration or measure the time relationship between changes in lung volume and HR. We used transfer function analysis to determine the magnitude and time relationship of the HR response to a known change in lung volume in controls and diabetics. This technique demonstrated significant differences between controls and diabetics with varying degrees of autonomic dysfunction. Specifically, reduced supine vagal and increased supine sympathetic HR modulation was found with progression of the autonomic neuropathy. In response to postural change the normal diabetics displayed impaired sympathetic HR modulation. Transfer function analysis yields new insight into the sequence of changes that occur with diabetic autonomic neuropathy and provides an accurate, easily comprehensible measurement of respiratory induced HR variability. PMID- 7800002 TI - Mixed nerve action potentials in acquired demyelinating polyneuropathy. AB - Uncertainty about motor and sensory contributions in abnormal nerves has limited the use of mixed nerve action potentials (MNAPs). We recorded MNAPs in 21 patients with an acquired demyelinating neuropathy, 18 age-matched control subjects, and 10 patients with an axonal polyneuropathy. Bipolar and unipolar recordings from median and ulnar nerves were made above the elbow after electrical stimulation of the nerves at the wrist. Antidromic digital sensory action potentials and motor conduction velocity were also recorded for both nerves. In 19 median and 12 ulnar nerves from demyelinating polyneuropathy patients, compared with control subjects, MNAP amplitudes were significantly reduced (mean, 6 microV vs. 31 microV), MNAP velocities were mildly reduced (mean, 50 m/s vs. 62 m/s), motor conduction velocities were significantly reduced (mean, 33 m/s vs. 57 m/s), and MNAPs were significantly dispersed, with markedly prolonged rise times (mean 2.0 ms vs. 1.0 ms). Compared with the axonal polyneuropathy group, MNAP amplitudes from the median nerve were similarly reduced (mean, 8 microV vs. 9 microV), MNAP velocities were only slightly slower (mean, 52 m/s vs. 58 m/s), but the rise times were significantly prolonged (mean, 2.0 ms vs 1.2 ms). We conclude that, in acquired demyelinating neuropathies, the onset and, in some cases, the whole MNAP is from afferent fibers, which can be abnormally dispersed, and that, over the same segment MNAP velocity is less affected than motor conduction velocity. PMID- 7800003 TI - Monoclonal antibodies against ICAM-1 and LFA-1 prolong nerve allograft survival. AB - In a rat nerve allograft model, specific immunosuppression was approached with monoclonal antibodies (MAbs) against cell-surface molecules. After engraftment, recipients were treated with antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) MAbs for 14 days. Functional recovery was evaluated biweekly. Electrophysiological and histological assessments were performed at 6 and 16 weeks. Immunologic responsiveness in the recipients was assessed with a cytotoxic T lymphocyte (CTL) assay at 16 weeks and skin grafts at 18 weeks. The untreated allograft group demonstrated complete disruption of fascicular architecture with poor nerve regeneration. The MAb treated allografts maintained well-organized nerve architecture with a dense population of well-myelinated fibers. These animals showed functional and electrophysiological recovery. Suppression of CTL activity was nerve donor specific and the survival time of nerve donor skin grafts was prolonged, suggesting induction of alloantigen-specific tolerance. MAbs therapy directed against ICAM-1/LFA-1 presents a new approach for the management of the peripheral nerve allograft response. PMID- 7800004 TI - Asthma and wheezing in the first six years of life. The Group Health Medical Associates. AB - BACKGROUND: Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. METHODS: In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age was available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the children's parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). RESULTS: At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [Vmax FRC]) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P < 0.001), to have elevated serum IgE levels (P < 0.01), to have normal lung function in the first year of life, and to have elevated serum IgE levels (P < 0.001) and diminished values for VmaxFRC (P < 0.01) at six years of age. CONCLUSIONS: The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma. PMID- 7800005 TI - Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. AB - BACKGROUND: There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications. We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents. METHODS: Patients with gastric ulcers seen on endoscopy and with H. pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day). Follow-up endoscopies were performed after five and nine weeks. The patients and their physicians were aware of the treatment assignments, but the endoscopists were not. RESULTS: A total of 100 patients were randomly assigned to treatment, and 85 completed the trial. At five weeks, H. pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001). The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28). At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0). The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial treatment group (P = 0.004). One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001). H. pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole. CONCLUSIONS: In patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence. PMID- 7800006 TI - Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. AB - BACKGROUND: Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow derived progenitors could reconstitute the lymphocyte population using a thymus dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. METHODS: We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. RESULTS: There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r = -0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r = 0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P = 0.015). CONCLUSIONS: Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy. PMID- 7800007 TI - Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin receptor gene. PMID- 7800008 TI - Images in clinical medicine. Post-tachycardia T-wave syndrome. PMID- 7800009 TI - Supraventricular tachycardia. PMID- 7800010 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises case 2-1995. A 71-year-old man with masses in the pancreas, presacral region, and left kidney. PMID- 7800011 TI - Asthma and wheezing in young children. PMID- 7800012 TI - Age, the thymus, and T lymphocytes. PMID- 7800013 TI - Thyrotropin-receptor mutations and thyroid dysfunction. PMID- 7800014 TI - G proteins in medicine. PMID- 7800015 TI - Female circumcision. PMID- 7800016 TI - Female circumcision. PMID- 7800018 TI - Treatment of acid reflux. PMID- 7800017 TI - Female circumcision. PMID- 7800019 TI - More on surveillance of children with medulloblastoma. PMID- 7800020 TI - Improvement of paraneoplastic opsoclonus-myoclonus after protein A column therapy. PMID- 7800021 TI - Heliox in respiratory failure from obstructive lung disease. PMID- 7800022 TI - More on fluoroquinolone antibiotics and tendon rupture. PMID- 7800023 TI - More on fluoroquinolone antibiotics and tendon rupture. PMID- 7800024 TI - Buying Editorials. PMID- 7800025 TI - Popper's achievement. PMID- 7800026 TI - Research integrity. PMID- 7800027 TI - Eighteen ninety five and all that. AB - Anniversarial commemorations this year include the discovery of X-rays, the calculation of the position of the undiscovered planet Neptune, the emergence of syphilis and the mandatory serving of lime juice to British sailors. PMID- 7800028 TI - Uprooting the human family tree. PMID- 7800029 TI - Kaposi's sarcoma. A finger on the culprit. PMID- 7800030 TI - Neurobiology. Cold, pain and the brain. PMID- 7800031 TI - Nature and Le Monde. PMID- 7800032 TI - Visual perception. Seeing backwards in time. PMID- 7800033 TI - Primatology. The price of being at the top. PMID- 7800034 TI - Holliday junctions cleaved by Rad1? PMID- 7800035 TI - US National Cancer Institute chief quits. PMID- 7800036 TI - Stochastic resonance and the benefits of noise: from ice ages to crayfish and SQUIDs. AB - Noise in dynamical systems is usually considered a nuisance. But in certain nonlinear systems, including electronic circuits and biological sensory apparatus, the presence of noise can in fact enhance the detection of weak signals. This phenomenon, called stochastic resonance, may find useful application in physical, technological and biomedical contexts. PMID- 7800037 TI - Acetylcholine receptor channel imaged in the open state. AB - The structure of the open-channel form of the acetylcholine receptor has been determined from electron images of Torpedo ray postsynaptic membranes activated by brief (< 5 ms) mixing with droplets containing acetylcholine. Comparison with the closed-channel form shows that acetylcholine initiates small rotations of the subunits in the extracellular domain, which trigger a change in configuration of alpha-helices lining the membrane-spanning pore. The open pore tapers towards the intracellular membrane face, where it is shaped by a 'barrel' of alpha-helices having a pronounced right-handed twist. PMID- 7800038 TI - Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. AB - There are many potential applications of 'intelligent' aqueous polymer systems in medicine, biotechnology, industry and in environmental problems. Many of these polymer systems undergo reversible phase transitions--for example, abrupt changes in volume--in response to external stimuli such as temperature, pH or the nature of the solvent. Most of the polymers studied previously are responsive to only one kind of stimulus. But for some applications, independent responsiveness to several factors, such as temperature and pH, may be required. Here we describe a polymer that undergoes marked solubility changes in water in response to temperature and/or pH changes. The polymer is prepared by grafting temperature sensitive side chains onto a pH-sensitive backbone. We also find that block copolymers, in which the temperature- and pH-sensitive units alternate along the chain, show similar behaviour. PMID- 7800039 TI - Reproductive constraints on aggressive competition in female baboons. AB - Competitive interaction between females of same social group is characteristic of most primate species. In Old World monkeys, females of high social rank maintain priority of access to scarce resources and harass low-ranking companions. But different field studies have found differing correlations between female dominance and reproductive success: several populations show an advantage of rank whereas others do not. Although such variation may reflect divergent levels of predation, food availability or social stress in different environments, female competitive ability may also be balanced by significant reproductive costs and thus be subject to strong stabilizing selection. We report here that high-ranking female baboons (Papio cynocephalus anubis) at Gombe National Park, Tanzania, enjoy shorter interbirth intervals, improved infant survival, and accelerated maturation of their daughters. These advantages, however, are countered by a significantly higher probability of miscarriage, and a proportion of high-ranking females suffer from reduced fertility. PMID- 7800040 TI - Visual attention modulates metacontrast masking. AB - How does the human visual system 'bind' different fragments in the visual scene to create enduring representations of objects? A visual illusion known as 'metacontrast' or backward masking provides compelling evidence that perception is not instantaneous and that it occurs sequentially in distinct stages. If a solid white target square is displayed for 50 ms in a tachistoscope, switched off, and followed by a 50 ms display of two flanking mask squares, remarkably, subjects report seeing only the two flanking squares: the first square is simply not 'seen'. By plotting the magnitude of masking as a function of the delay between the target and mask (the stimulus onset asynchrony), one can obtain a characteristic 'U'-shaped function with optimum masking occurring at about 50 ms, and no masking with synchronous target and mask presentations or at delays higher than 300 ms. The illusion is also highly sensitive to elementary stimulus dimensions such as colour, orientation and spatial frequency, and it has been suggested that it is based on 'low level' autonomous visual mechanisms rather than cognitive processes. Here we describe a novel visual stimulus that demonstrates that metacontrast can be strongly modulated by 'top down' influence such as voluntary visual attention. PMID- 7800041 TI - Increased male fertility in Tribolium confusum beetles after infection with the intracellular parasite Wolbachia. AB - The cytoplasmically inherited microorganism Wolbachia pipientis behaves like a sexually selected trait in its host, the flour beetle Tribolium confusum, enhancing male fertility at the expense of female fecundity. Here we show that infected females have fewer offspring than uninfected females but infected males have a large fertility advantage over uninfected males within multiply inseminated infected or uninfected females. The male fertility effect accelerates the spread of the Wolbachia through the host population and expands the initial opportunity for hitch-hiking of host nuclear genes. Sperm competition in a host, mediated by endosymbionts, has not been previously described. PMID- 7800042 TI - A transcription factor controlling development of peripheral sense organs in C. elegans. AB - The basic-helix-loop-helix (bHLH) proteins constitute a class of transcription factors thought to be important in the control of cell-type determination. These transcription factors are believed to activate the expression of cell-type specific genes to generate stable differentiated cell types. The expression of bHLH proteins, in turn, is regulated by spatial cues, so that switches in cell type occur in a reproducible pattern. We report here that the lin-32 gene of Caenorhabditis elegans, which encodes a bHLH protein of the Drosophila achaete scute family of transcription factors, is necessary and in some cells sufficient for specification of the neuroblast cell fate. Similarity in the function and structure of the lin-32 protein (LIN-32) to transcription factors of the achaete scute gene family in Drosophila and vertebrates implies that this class of transcription factors functioned in a primitive ancestral form to specify neuronal cell fate, supporting the proposition that certain basic mechanisms of cell-type determination have been conserved through metazoan evolution. PMID- 7800043 TI - Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. AB - Cell cycle progression in eukaryotes is controlled by the p34cdc2/CDC28 protein kinase and its short-lived, phase-specific regulatory subunits called cyclins. In Xenopus oocytes, degradation of M-phase (B-type) cyclins is required for exit from mitosis and is mediated by the ubiquitin-dependent proteolytic system. Here we show that B-type-cyclin degradation in yeast involves an essential nuclear ubiquitin-conjugating enzyme, UBC9. Repression of UBC9 synthesis prevents cell cycle progression at the G2 or early M phase, causing the accumulation of large budded cells with a single nucleus, a short spindle and replicated DNA. In ubc9 mutants both CLB5, an S-phase cyclin, and CLB2, an M-phase cyclin, are stabilized. In wild-type cells the CLB5 protein is unstable throughout the cell cycle, whereas CLB2 turnover occurs only at a specific cell-cycle stage. Thus distinct degradation signals or regulated interaction with the ubiquitin-protein ligase system may determine the cell-cycle specificity of cyclin proteolysis. PMID- 7800045 TI - DNA structure-dependent requirements for yeast RAD genes in gene conversion. AB - In Saccharomyces cerevisiae, HO endonuclease-induced mating-type (MAT) switching is a specialized mitotic recombination event in which MAT sequences are replaced by those copied from a distant, unexpressed donor (HML or HMR). The donors have a chromatin structure inaccessible for both transcription and HO cleavage. Here we use physical monitoring of DNA to show that MAT switching is completely blocked at an early step in recombination in strains deleted for the DNA repair genes RAD51, RAD52, RAD54, RAD55 or RAD57. We find, however, that only RAD52 is required when the donor sequence is simultaneously not silenced and located on a plasmid. RAD51, RAD54, RAD55 and RAD57 are still required when the same transcribed donor is on the chromosome. We conclude that recombination in vivo occurs between DNA molecules in chromatin, whose structure significantly influences the outcome. RAD51, RAD54, RAD55 and RAD57 are all required to facilitate strand invasion into otherwise inaccessible donor sequences. PMID- 7800044 TI - Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. AB - Ubiquitination of proteins involves the concerted action of the E1 ubiquitin activating enzyme, E2 ubiquitin-conjugating enzymes and E3 ubiquitin-protein ligases. It has been proposed that E3s function as 'docking proteins', specifically binding substrate proteins and specific E2s, and that ubiquitin is then transferred directly from E2s to substrates. We show here that formation of a ubiquitin thioester on E6-AP, an E3 involved in the human papillomavirus E6 induced ubiquitination of p53 (refs 6-10), is an intermediate step in E6-AP dependent ubiquitination. The order of ubiquitin transfer is from E1 to E2, from E2 to E6-AP, and finally from E6-AP to a substrate. This cascade of ubiquitin thioester complexes suggests that E3s have a defined enzymatic activity and do not function simply as docking proteins. The cysteine residue of E6-AP responsible for ubiquitin thioester formation was mapped to a region that is highly conserved among several proteins of unknown function, suggesting that these proteins share the ability to form thioesters with ubiquitin. PMID- 7800046 TI - Eye-lens proteins: structure, superstructure, stability, genetics. AB - The eye lens in vertebrates and invertebrates is an avascular tissue which allows one to focus objects on the retina. The lens grows throughout life, maintaining transparency without significant turnover of its densely packed proteins. Apart from cytoskeletal and taxon-specific components, these proteins belong mainly to the alpha- and beta gamma-crystallin families. The detailed structural analysis of beta gamma-crystallins can explain the anomalous stability by the specific supersecondary structure ("Greek key" topology) of the domains and by strong domain and subunit interactions. The spatial correlation of the molecules at the given high concentrations in the fiber cells gives rise to "short-range order" with minimum light scattering, thus providing optimum transparency of the eye lens. PMID- 7800047 TI - [Light regulation of chloroplast enzymes]. AB - The activity of various chloroplast enzymes is regulated by a covalent redox modification cycle driven by photosynthetic electron flow and oxygen, and is fine tuned by effectors specific for each target enzyme. The regulatory principle resembles the protein phosphorylation/dephosphorylation system. The primary structures of some redox-modulated enzymes reveal characteristic extra cysteine carrying peptides in addition to very conserved sequences. PMID- 7800048 TI - The nature of mercury in tap water. PMID- 7800049 TI - Transformation of the mycotoxin ochratoxin A in wheat and maize cell suspension cultures. PMID- 7800050 TI - Sex linkage in the honeybee Apis mellifera detected by multilocus DNA fingerprinting. PMID- 7800051 TI - Substance abuse treatment modalities. PMID- 7800052 TI - Illiteracy still a problem. PMID- 7800053 TI - "No fault," round three. PMID- 7800054 TI - "No fault", round three. PMID- 7800055 TI - Second-look laparoscopy. PMID- 7800057 TI - Facing the challenge of HIV. Primary care physicians have an obligation to care for those infected. PMID- 7800056 TI - Necrotizing fasciitis and myositis caused by group A streptococci. Epidemiology, diagnosis, and treatment of "flesh-eating bacteria". AB - Despite the absence of conclusive proof, the incidence of necrotizing fasciitis and myositis due to GAS may be increasing, possibly related to shifts in the proportion of GAS isolates of M-Types 1 and 3. These M-types (or the production of exotoxins and proteases associated with them) may lead to severe GAS infections in individuals who lack immunity. Recent television and newspaper reports underscore the potential virulence of GAS even in young and previously well individuals although they do this at the expense of raising fear in the general population. It is unfortunate that these reports often fail to emphasize the rarity with which GAS causes myositis and fasciitis. The overall incidence of these dreadful diseases is very low. In fact, by extrapolating the CDC estimates, we suspect that only 14-40 cases of GAS-induced myositis or fasciitis occur annually in North Carolina. Each of these infections is a true calamity for the affected patients and their physicians, but together they represent only a tiny fraction of all GAS infections that occur in North Carolinians each year. It is relatively easy to separate uncomplicated streptococcal cellulitis from GAS induced fasciitis and/or myositis by bedside exam and old-fashioned clinical judgment. Prompt and aggressive surgical debridement and antibiotic therapy are needed for all patients with myositis and/or fasciitis due to GAS; others can be treated with simple beta-lactam antibiotics and careful observation. PMID- 7800058 TI - HIV testing: a medical student's perspective. PMID- 7800059 TI - Can physicians deny treatment based on fear of AIDS infection? PMID- 7800060 TI - Managing medicine: "Dr." stands for doctor and director. PMID- 7800061 TI - Dermatology. Your skin. PMID- 7800062 TI - The use of donated oocytes for the treatment of infertility. PMID- 7800063 TI - Development of sports medicine. PMID- 7800064 TI - Continuing medical education in North Carolina. Emerging trends and new challenges. PMID- 7800065 TI - Patients suffer pyrogenic reactions in Philadelphia dialysis units. PMID- 7800066 TI - Dedication, ingenuity guide inventors in better the lives of kidney patients. Moncrief, Popovich receive NN&I's Quality of Life Award. PMID- 7800067 TI - Evaluation: a progress report on measuring ESRD outcome. PMID- 7800068 TI - International health care models: a comparative analysis. Part II. PMID- 7800069 TI - OIG scrutinizing lab discounting for dialysis units. PMID- 7800070 TI - [Mild exertional dyspnea is sometimes a serious symptom]. PMID- 7800071 TI - [Therapeutic inhalation of nitric oxide in patients with pulmonary hypertension]. PMID- 7800072 TI - [Carotid body tumors]. PMID- 7800073 TI - [Value of serological determinations in the differential diagnosis of ulcerative colitis and Crohn's disease, and immunogenetic aspects]. PMID- 7800074 TI - [Characteristics of patients with recurrence of primary melanoma at least 10 years following surgical treatment]. AB - OBJECTIVE: Assessment of incidence and risk factors of late recurrence (after a disease-free interval of at least 10 years) following treatment for primary melanoma. METHODS: Retrospective study taking into account a total of 2579 melanoma patients admitted to the Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis in the period 1956 to 1991; patients with ocular melanoma were excluded. RESULTS: Twenty-three patients had a disease-free interval of at least 10 years (median 11 years; range: 10-21) after treatment for primary melanoma: 17 women and 6 men, with a median age of 43 years (20-62). This group predominantly consisted of women with a primary melanoma localised on the extremities. Most of them had melanomas of intermediate thickness (Breslow thickness: 1-2 mm). Patients with a first recurrence locoregionally (16) had a 5-year survival rate of over 50%; 6 of the 7 patients with a first relapse at distant sites died within a few months. CONCLUSION: Melanoma patients who are discharged from follow up after a disease-free interval of 10 years are advised to continue loco regional self-examination. PMID- 7800075 TI - [Risk of tuberculosis in the inadequate handling of refugees seeking asylum]. AB - OBJECTIVE: To describe screening for tuberculosis in a temporary centre for refugees, and contact investigation after a patient with open tuberculosis had been identified. DESIGN: Descriptive. SETTING: Regional Communal Health Centre Nijmegen. METHOD: The refugees waiting for official status were housed on three cruise ships during the winter period November 1993 to April 1994. Ventilatory capacity was insufficient. The people had thorax radiograms after 10 days on average as a screening for tuberculosis. When abnormalities were found sputum was examined (Ziehl-Neelsen staining and culture). The workers of the centre were Mantoux-tested. RESULTS: Of the 834 persons screened 4 had open tuberculosis. Contact investigation yielded three cases of infection among 5 contacts in the first ring, and 11 cases of infection and 2 cases of tuberculosis (one infiltrative pulmonary tuberculosis, the other cavernous pulmonary tuberculosis) among 215 contacts in the second ring. Fourteen of the infected persons were centre workers. The bacteria found were not resistant to tuberculostatics. CONCLUSION: Rapid transmission of tuberculosis occurred because of insufficient ventilation and a slow screening procedure. Tuberculosis in refugee centres is a serious problem that needs adequate attention. PMID- 7800076 TI - [Pulmonary hypertension following use of fenfluramine for obesity]. AB - Pulmonary hypertension was diagnosed in a 41-year-old woman after 16 months' use of fenfluramine as a treatment for obesity. Despite discontinuation, pulmonary pressure remained elevated. Drug-induced pulmonary hypertension is rare but has been reported relatively often after use of the sympathicomimetic agent aminorexfumarate, but also, although more rarely, of fenfluramine. PMID- 7800077 TI - [Nitric oxide to combat pulmonary hypertension in an infant following heart surgery for septum defect]. AB - A 5-month-old female infant with Down syndrome underwent surgical repair of a complete atrioventricular septal defect and a patent ductus arteriosus. The postoperative course was complicated by life-threatening pulmonary hypertensive crises which did not respond to conventional vasodilating therapy. Nitric oxide inhalation resulted in rapid decrease in pulmonary artery pressure and improvement of haemodynamics and oxygenation without causing any untoward side effects. Inhalation of NO was continued over the next 4 days, with a maximum NO concentration of 20 ppm during a period of 12 hours. The subsequent postoperative course was uneventful and the patient was discharged from the hospital in good health on the 23rd postoperative day. PMID- 7800078 TI - [Minors and mentally incompetent adult patients in the Law on Medical Treatment Agreement]. PMID- 7800079 TI - [Medical treatment of mentally incompetent patients in the Law on Medical Treatment Agreement]. PMID- 7800080 TI - [Manganese poisoning due to the use of Chien Pu Wan tablets]. PMID- 7800081 TI - [Manganese poisoning due to the use of Chien Pu Wan tablets]. PMID- 7800082 TI - [Disciplinary decisions and anesthesiological practice management]. PMID- 7800083 TI - [Euthanasia; confusion concerning the reporting procedure]. PMID- 7800084 TI - [No positive effect of preoperative exercise therapy and instruction in patients about to undergo hip arthroplasty]. PMID- 7800085 TI - [The Law on Mass Screening]. PMID- 7800086 TI - [Current status and developments in psychiatric care. A European comparison]. AB - In most European countries several reform indicators point to a marked change in psychiatric care during the last three decades. Almost everywhere the size of psychiatric hospitals was reduced and the number of beds decreased. The development in the outpatient and complementary sector is less clear. Different European countries provide sheltered living accomodations, workshops and outpatient treatment to varying degrees. Comparably complex are financing and legal grounds of psychiatric treatment. Beside still existing institutional deficits, the negative attitude of the public toward mentally ill and psychiatric care is a serious obstacle for further implementation of community based psychiatric care. PMID- 7800088 TI - [Positive or negative symptoms. Which are more reliable in the diagnosis of schizophrenia?]. AB - Due to the anticipated revisions concerning diagnostic criteria for schizophrenia in DSM-IV, recent Anglo-American research has been particularly concerned with the controversial problem whether positive or negative symptoms are more suited for the determination of these criteria. We addressed this problem in an empirical study. A total of 489 consecutive admissions to the Department of Psychiatry at the RWTH University, Aachen were assessed for the distribution of positive, negative and basic symptoms according to six ICD-10 double-digit diagnostic categories. Positive symptoms were shown to be more useful for diagnosis than the negative or basic symptoms. Basic symptoms, however, had a pattern of distribution which supports the notion that they may also be useful for the early diagnosis of schizophrenia. PMID- 7800087 TI - [Detection of early warning signs in schizophrenic patients. Possible applications in prevention of recurrence]. AB - In the treatment of schizophrenia, two new strategies have been developed with the aim of adequate relapse prevention accompanied by lowest possible risk of side-effects. One strategy is to have the patient continue to take medication at a highly reduced dosage (10-20% of the standard dose). The other is to gradually stop neuroleptic medication after remission and to reinstitute medication only in the case of prodromal symptoms (termed targeted or intermittent treatment). According to Herz and Melville [13] many schizophrenic patients show signs of relapse well before recurrence of overt psychotic features. Monitoring to detect prodromal symptoms is especially important in targeted treatment because, otherwise, neuroleptic medication often cannot be initiated in time. In the present study of 51 schizophrenic patients we were able to replicate the results of Herz & Melville in the German-speaking countries. Prior to acute exacerbation of psychosis, most patients experience alterations of feelings and behaviour. These alterations may also be recognized by family members. Such early warning signs of relapse mainly consist of non-specific, non-psychotic symptoms: tenseness and nervousness, eating less, trouble concentrating and sleeping, depressive mood and seeing friends less. Furthermore, the regular monitoring and use of early warning signs specific to each patient in the aftercare of schizophrenic patients seems to be practicable, especially in psychoeducative family therapy. PMID- 7800090 TI - [Locus of control in chronic schizophrenia. Empirical data in an ambulatory group of patients]. AB - In the present study loci of control as cognitive attitudes are investigated by repeated examinations in an out-patient therapy group of patients suffering from chronic schizophrenia. Loci of control are expressions of subjective intellectual evaluations to give an opinion of individual results of action. Present study data agree with first results in literature which show an external orientation of investigated patients and the constant markedness of cognitive attitudes in time. Furthermore study results about the connection of cognitive attitudes and psychopathological self ratings and ratings by the investigator as well as statements about changes of experience and behaviour are shown and discussed in the end. It is started out that knowledges of these cognitions can support long term out-patient care of patients with chronic schizophrenia. The consideration of cognitive attitudes is part of a concept of therapeutic interventions, which improve personal skills by finding a model of illness. PMID- 7800089 TI - [Prenatal developmental disorders of brain structures in schizophrenic psychoses]. AB - In recent years neuroimaging techniques have revealed various cerebral and structural variances in patients with schizophrenic psychoses. The best established findings are the enlargement of the lateral ventricles and discrete structural deficits in temporobasal structures of the cortex. Neuropathological investigations have detected subcortical as well as cortical variances. Subcortically, the volume of the striatum and the globus pallidus have been found to be enlarged in schizophrenics. Among the cortical deviations, the cytoarchitectonic disturbances of the rostral entorhinal region have been well documented and are especially important. According to neuropathological criteria, they are derived from disturbances of prenatal cell migration within the central nervous system. Due to its close anatomical and functional connection with the hippocampal formation and its being the assembly point of all sensory cortical areas, disturbances of this area could seriously impede the processing and filtering of information within the limbic system. The other hitherto reported structural anomalies, such as the disturbance to the radial order of hippocampal neurons, and the abnormal structures in the frontobasal orbital regions and the rostroventral insula, could be connected to the disturbances of migration within the entorhinal region; the former could be secondary, but still prenatal developments. Well documented are the architectonic changes in the rostral cingulate gyrus which is itself connected with the entorhinal region via the Papez circuit. These findings are supported and supplemented by the results of epidemiological studies which indicate a disturbance of brain development during the second trimenon of the prenatal period. Viral infections (Influenza A2) of mothers during this critical period appear to play an especially important role.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800091 TI - [The world as inner space. Kafka's "The Burrow" as a paradigm of paranoid spatial experience]. AB - The paranoid's experience of space is illustrated in the present study by means of an investigation of paraphrenic senile psychosis and an analysis of Kafka's short story, "The Burrow". This may be characterized as an experience of increasing permeability and disintegration of boundaries between one's own, private space and that belonging to others, or between inside and outside. At first, a latent ego-weakness is compensated by shifting the self-boundaries onto the territory of one's dwelling which serves as an "external shell" for the self. The emphasis on fencing-off and isolation from the external world, however, renders the hidden, inner spaces ever more threatening. The protecting barriers change into fragile facades through which enemies are able to attack. Finally, the sheltering but, nevertheless, exposed inner spaces fall prey to threats from the outside. Paradoxically, the disintegration of the inner space of self comes about by the paranoid constantly taking the view point of his fictitious enemies; he, thereby, sees through and penetrates the very barriers which he himself has erected. PMID- 7800092 TI - [Selective serotonin reuptake inhibitors in treatment of compulsive symptoms within the scope of schizophrenia]. AB - We report the case history of two female schizophrenic in-patients who exhibited a significant reduction of accompanying obsessive-compulsive symptoms under the combined treatment of neuroleptics and selective serotonin reuptake inhibitors (SSRIs). Our results indicate that the basic psychotic disorder was not exacerbated as a result of this additional treatment. PMID- 7800093 TI - [Drug treatment of schizophrenic psychoses in puerperium]. AB - Three schizophrenic patients and one schizophreniform patient, all experiencing puerperal psychosis, required a drug-induced delactation (bromocriptine) simultaneously to neuroleptic treatment. Taking into account the pharmacodynamic effects, an exacerbation of symptoms following bromocriptine (a D-2 receptor agonist) and an impairment of delactation following neuroleptic treatment (bringing about the blockade of D-2 receptors) are to be expected. In three cases, we carried out a combined bromocriptine-haloperidol treatment and, in one case, a bromocriptine-clozapine treatment. The above mentioned complications were not observed in any of the cases. The problems which may result from using clozapine during the puerperal period are also discussed. PMID- 7800094 TI - [Early dyskinesia with administration of clozapine (Leponex)]. AB - A 51-year old, female patient suffering from schizophrenic disorder was treated with clozapine (Leponex). Four hours after the first parenteral, drug administration, she developed an acute dyskinesia. PMID- 7800095 TI - [Hypothermia caused by neuroleptics. 2 case reports and review of the literature]. AB - The present paper discusses appearance and course of neuroleptic induced hypothermia of a 36 years old woman suffering from periodic catatonia and a 38 years old seriously mentally handicapped man. Analysis of clinical studies and pharmacological tests with animals about body temperature changes caused by neuroleptics yields that these may lead to hypothermia as well as hyperthermia, depending on individual disposition and dose, which is mainly a result of their effect through dopaminergic neurons of the hypothalamus, which controls thermoregulation, and of their influence on vasomotoric mechanisms of vessels of the skin. Though hyperthermic changes are more hazardous and occur more frequently hypothermia by neuroleptic agents is clinically relevant as shown by the summarizing presentation of previously released case reports: hypothermia is found at neuroleptic medicated healthy volunteers and at psychiatric patients with or without physical illness, at which hypothyreosis and impair of the brain seem to represent special risks. PMID- 7800097 TI - [Schizophrenia: new results and models of the etiology]. PMID- 7800096 TI - [Apolipoprotein E typology and dementia]. PMID- 7800098 TI - [Is psychoanalytic psychotherapy an "alternative method"]. PMID- 7800099 TI - [Is psychoanalytic psychotherapy an "alternative method"]. PMID- 7800100 TI - [Is psychoanalytic psychotherapy an "alternative method"]. PMID- 7800101 TI - Stroke data banks: challenges for research. Geneva, Switzerland, May 1993. Workshop proceedings. PMID- 7800102 TI - Overview of stroke data banks. AB - Stroke data banks (SDBs) used for clinical research are between traditional case series and population-based studies. They can serve a multitude of purposes: estimating the burden of disease treated in one or several centers, calculating the recruitment rates for clinical trials, or for the detection of stroke incidence or time trends by means of a long-time observation in a defined geographical area. Some SDBs restrict themselves to the systematic collection of rare cases of stroke or to recurring strokes. The strength of an SDB lies in its ability to accumulate a large set of data within specified time frames using a defined set of diagnostic procedures. One of the most attractive features of an SDB is its generation of research hypotheses that allow one to look for similar patterns in related and in unrelated disorders. The overview in this volume is based on a literature search of SDBs published since 1980 and a questionnaire sent to the principal investigators applying ten criteria considered essential for clinical research: diagnostic criteria, separate analysis of first-ever strokes, CT investigation rate > 70%, integration of autopsy data, collection of prospective data wherever possible, planning of a pilot phase and interrater studies, constant screening procedures to identify patients enrolled and constant time frame of examinations, a large spectrum of clinical and investigative data, 12 months' follow-up examinations, and a baseline paper describing the procedures used. When applying these criteria to the literature only 8 SDBs fulfilled them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800103 TI - Issues in analyzing data: experiences with three data bases. AB - Analytic issues in stroke data base research are reviewed, drawing upon relevant experiences in the analyses of three observational data bases from a variety of clinical fields. The specifics of the data base construct, statistical issues and variations in possible interpretations of results are discussed. Responsible analyses of and conservative inferences from observational data bases are stressed. PMID- 7800104 TI - Observational data bases in neurological disorders: selection bias and generalization of results. AB - Observational data bases in the neurological disorders may be an important source of information on etiology and natural history. The ability to make valid generalizations of results from a data base to the general population of patients with a particular disorder is not, however, guaranteed. The design or analysis of the study may result in selection biases that make inferences untenable. Examples are presented which demonstrate the potential for bias limiting the validity of inferences beyond the sample observed. PMID- 7800105 TI - Interactions between stroke data banks and clinical trials. AB - The number of clinical trials to evaluate new therapies for stroke treatment and prevention is growing rapidly. Although stroke data banks cannot answer treatment efficacy questions, they can have powerful interactions with the design and conduct of clinical trials. Through data banks one can generate hypotheses regarding treatment, estimate the frequency of outcome events, calculate sample size, determine stratification factors that may or may not be needed in a clinical trial, establish inclusion and exclusion criteria and decide on the elements to include in the data collection forms. Using a data bank one can estimate the number of patients that may be screened, eligible, refused, and enrolled in a clinical trial with given inclusion and exclusion criteria. Data banks are helpful for surveillance of all eligible subjects and calculating the proportion of the total cases who were randomized. With the more widespread analyses of stroke data banks we can design focused clinical trials and reach some definitive conclusions regarding the future treatment of stroke. PMID- 7800106 TI - Baseline measures and outcome predictions. AB - This paper reviews the methodological issues in the epidemiological study of the outcome from stroke. Data are presented from an unselected series of patients in whom the underlying stroke pathology is clearly defined. Although the natural history varies among the different pathological subtypes of stroke, simple clinical baseline measures of the severity of the neurological deficit (incontinence, loss of consciousness and severity of paresis) and premorbid level of disability and social functioning independently predict disability-free survival by 1 year, and may help direct management and research. PMID- 7800107 TI - Clinical methods for diagnostic confirmation of stroke subtypes. AB - Clinicians faced with a patient having a sudden-onset, focal neurological deficit must answer three fundamental questions: is it a stroke?, is it ischemia or hemorrhage? and what kind of ischemic stroke is it? Clinical information (that is, history and examination) is immediately available to every physician, and its role in answering these questions is extremely important, even though a 100% certainty can only be obtained with instrumental diagnostic tools. In fact, when diagnosis is based on properly designed clinical criteria, the percentage of diagnostic mistakes is quite low. Clinical methods are still the best way of orientating topographic and etiologic diagnosis, as well as prognosis. In addition, time might be saved if randomization in clinical trials could be done using clinical methods before complex investigations are applied. PMID- 7800108 TI - Value of stroke data banks for the analysis of clinical syndromes. AB - The diversity of clinical syndromes and etiologies of stroke make stroke data banks one of the best tools to improve current knowledge of stroke. Hospital based registries profit from a stroke team in the acute phase of the event and from access to special investigations. This leads to an earlier clinical and topographic diagnosis that may allow inclusion of the patient into acute trials within the therapeutic window. It also makes possible complete investigation in the acute period and broadens information on potential etiologies. PMID- 7800109 TI - Black-white differences in stroke frequency: challenges for research. AB - Studies of ethnic differences in frequency of disease can sometimes provide insights into etiologic mechanisms and, hopefully, lead to interventions that decrease risk and frequency of the disease. This principle can be applied to studies of stroke among blacks and whites. Blacks carry a disproportionate burden of strokes relative to the number of blacks in the population. In this paper, possible explanations for the differences are reviewed. It has been reported that certain risk factors for stroke, notably hypertension, are more common in blacks. However, it is unclear whether less access to medical care, difficulty with compliance in treatment programs, genetic differences in responsiveness to certain drugs or other genetic differences related to susceptibility are responsible for the consistently higher stroke frequency in blacks compared to whites. The frequency of stroke type also differs in these ethnic groups; whites are more prone to large vessel and embolic strokes whereas blacks suffer a higher frequency of small vessel and hemorrhagic stroke. When closely examining evidence, it is also unclear whether life-style, socioeconomic, or other factors can be implicated and even whether race plays any important role at all. All of these ethnic issues must carefully be considered in stroke data base research. PMID- 7800110 TI - Assessment of cerebrovascular risk profiles in healthy persons: definition of research goals and the Austrian Stroke Prevention Study (ASPS). AB - The advent of new laboratory methods and noninvasive imaging modalities has extended the diagnostic possibilities in normal individuals. This article elaborates the new options for the assessment of stroke risk offered by these techniques. In this context we present the Austrian Stroke Prevention Study, which is the first prospective long-term investigation of normals that includes Doppler sonography, magnetic resonance imaging and single photon emission computed tomography. The design, utility and limitations of this study are discussed. PMID- 7800111 TI - Quantitative assessment of carotid atherosclerosis in a healthy population. AB - To evaluate the prevalence and extent of carotid atherosclerosis in a general healthy population, duplex ultrasound imaging was performed in 909 men and women aged 40-79 years as part of the prospective Bruneck Ischemic Heart Disease and Stroke Prevention Study. Atherosclerotic lesions were found in 47.8% of men and 36.3% of women. Sex differences in the prevalence rates were most pronounced from age 40 to 60 years with a convergence occurring in the 7th decade. The age range of 60-69 years was found to be the crucial period for the development of advanced carotid artery disease. The frequency of internal carotid artery stenosis (> 50%) in elderly men and women (60-79 years) was 10.5 and 5.5%. In nonstenotic carotid artery disease the lumen diameter turned out to be a useful indirect measure of the vascular status. PMID- 7800112 TI - Cardioembolic stroke: results from three current stroke data banks. AB - About 17% of all transient ischemic attacks (TIA) and ischemic strokes were due to cardiogenic embolism in three prospective stroke registries (Berlin, Giessen, Klosterneuburg). Most of these patients can be identified by history, clinical examination, conventional ECG, and appropriate use of echocardiography. Widespread screening of stroke patients with transesophageal echocardiography, as intented in the protocol of two registries, did not appreciably increase the portion of patients with the final diagnosis of cardiogenic embolism, although, in many cases, minor-risk embolic sources can be identified. Prognosis for death or early recurrence after cardiogenic brain embolism was not worse than assumed previously. PMID- 7800113 TI - Pathophysiologic assessment of data from a stroke data bank. AB - Stroke data banks have been instrumental in helping us to clarify stroke etiology and in the investigation of clinical-topographic correlations. For these purposes they have relied upon results from noninvasive vascular and cardiac methods, including extra- and transcranial Doppler sonography and echocardiography, as well as from procedures such as cranial computed tomography and magnetic resonance imaging. Conventional database concepts have also been used to assess pathophysiologic aspects of stroke. Although such applications have made important contributions in this multidiscipline area of investigation, they are limited by a lack of explicit representation of pathophysiologic knowledge for data interpretation. Recent results from artificial intelligence research suggest exciting new frontiers for medical database design with concepts stemming from second generation expert systems. We propose an extended concept for stroke data banks to include a knowledge-based system which incorporates current patient data, heuristic knowledge relating clinical features to functional impairment, and pathophysiologic models of neurological disease. PMID- 7800114 TI - The position of neuroimaging in the evaluation of stroke risk. PMID- 7800115 TI - Problems encountered with longitudinal neurological, psychometric and cerebral CT imaging among stroke data bank patients with dementia. AB - 41 patients (30 men, 11 women, mean age 65.3 +/- 9.7 years) with probable ischemic vascular dementia diagnosed according to stated clinical criteria at least 3 months after hospital discharge and among a few nonhospitalized subjects with thorough clinical, neurovascular and neuroimaging workup have been followed for the past 7 years with serial measures of neurological and cognitive status and cerebral blood flow using stable xenon-enhanced CT. Cognitive impairments correlated with cerebral ischemia rather than CT measurements of infarcted brain volume. A minimum of one follow-up was required and follow-up intervals ranged from 4 months to 6.6 years (mean 3.4 +/- 1.6 years). 9 patients (22.0%) were lost to follow-up, 4.9% died, 9.8% became incapacitated by additional strokes, 2.4% by cancer and 4.9% moved away. Cross-sequential designs adjust for problems of attrition. Mortality rates of 1.4%/year during 1986-1993 are significantly lower than 2.0%/year between 1983 and 1986. Declines in mortality are attributed to control of risk factors and antiplatelet treatment of atherosclerotic cerebral vascular disease and anticoagulant treatment of patients with cardiogenic embolism. PMID- 7800116 TI - Developmental expression of MOSP in cultured oligodendrocytes. AB - Myelin/oligodendrocyte specific protein (MOSP) is a recently characterized 48 kDa surface membrane protein that is expressed exclusively by oligodendrocytes in the CNS. In this report, evidence is presented for the identification of the stage in the oligodendrocyte lineage when MOSP is first expressed. MOSP initially appears on immature oligodendrocytes about four to five days postnatal, which is about one to two days after the appearance of galactocerebroside and sulfatide. The initial expression of MOSP occurs at the stage in development when oligodendrocytes are elaborating processes and just beginning to form membrane sheets. Since 1) MOSP is capable of signaling increases in microtubular structures in oligodendrocytes and 2) microtubular structures may be essential for extension of growing processes and the formation of membrane sheaths, MOSP may play an important role in differentiation of oligodendrocytes and the formation of myelin. PMID- 7800118 TI - Identification of novel mRNAs expressed in oligodendrocytes. AB - To identify new proteins, which are expressed in oligodendrocytes and which may have a functional role in myelination, a rat oligodendrocyte cDNA library was screened using differential and subtractive screening techniques. Ten clones that have elevated levels of expression in brain were isolated. Two of these clones were characterized further and one clone, pC26.H2, was found to be closely related to mouse stearoyl-CoA desaturase 2 (SCD2), which catalyzes the synthesis of unsaturated fatty acid. From Northern blot and in situ hybridization studies, SCD2 mRNA was expressed primarily in brain with lower levels found in lung and spleen. In brain sections, SCD2 mRNA was found primarily in oligodendrocytes, although mRNA was detected at a low level in neurons, in particular in Purkinje cells in the cerebellum. Northern blot analysis of the other clone, p973.HB, indicated that it was expressed more selectively in brain. In mixed glial cultures oligodendrocytes were the only cells that expressed this mRNA, whereas in brain, neurons expressed this mRNA at a higher level than in oligodendrocytes. This clone is being actively pursued because of its unique expression exclusively in oligodendrocytes and neurons. PMID- 7800119 TI - In vitro analysis of ion channels in periaxolemmal-myelin and white matter clathrin coated vesicles: modulation by calcium and GTP gamma S. AB - This study reports the analysis of K+ channel activity in bovine periaxolemmal myelin and white matter-derived clathrin-coated vesicles. Channel activity was evaluated by the fusion of membrane vesicles with phospholipid bilayers formed across a patch-clamp pipette. In periaxolemmal myelin spontaneous K+ channels were observed with amplitudes of 25-30, 45-55, and 80-100 pS, all of which exhibited mean open-times of 1-2 msec. The open state probability of the 50 pS channel in periaxolemmal-myelin was increased by 6-methyldihydro-pyran-2-one. Periaxolemmal-myelin K+ channel activity was regulated by Ca2+. Little or no change in activity was observed when Ca2+ was added to the cis side of the bilayer. Addition of 10 microM total Ca2+ also resulted in little change in K+ channel activity. However, at 80 microM total Ca2+ all K+ channel activity was suppressed along with the activation of a 100 pS Cl- channel. The K+ channel activity in periaxolemmal myelin was also regulated through a G-protein. Addition of GTP gamma S to the trans side of the bilayer resulted in a restriction of activity to the 45-50 pS channel which was present at all holding potentials. Endocytic coated vesicles, form in part through G-protein mediated events; white matter coated vesicles were analyzed for G proteins and for K+ channel activity. These vesicles, which previous studies had shown are derived from periaxolemmal domains, were found to be enriched in the alpha subunits of G0, Gs alpha, and Gi alpha and the low molecular weight G protein, ras.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800120 TI - Special issue dedicated to Dr. Marjorie B. Lees. PMID- 7800117 TI - Brain, liver, and adipose tissue erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treated with glyceryl trierucate and trioleate oils (Lorenzo's oil). AB - Brain, liver, and adipose lipids were studied in the postmortem tissues of four adrenoleukodystrophy patients who had been treated with a mixture of glyceryl trioleate and trierucate oils ("Lorenzo's Oil") and compared to 7 untreated ALD patients and 3 controls. The dietary therapy appeared to reduce the levels of saturated very long chain fatty acids in the plasma, adipose tissue and liver; in the brain they were reduced in only one of the four patients. While substantial amounts of erucic acid were present in some of the tissues even 12 months after therapy had been discontinued, the levels in brain did not exceed those in controls at any time. The failure of erucic acid to enter the brain in significant quantity may be a factor in the disappointing results of dietary therapy for adrenoleukodystrophy. PMID- 7800123 TI - Plasmolipin: the other myelin proteolipid. A review of studies on its structure, expression, and function. PMID- 7800121 TI - Overview: protein palmitoylation in the nervous system: current views and unsolved problems. AB - Palmitoylation refers to a dynamic post-translational modification of proteins involving the covalent attachment of long-chain fatty acids to the side chains of cysteine, threonine or serine residues. In recent years, palmitoylation has been identified as a widespread modification of both viral and cellular proteins. Because of its dynamic nature, protein palmitoylation, like phosphorylation, appears to have a crucial role in the functioning of the nervous system. Several important questions regarding the post-translational acylation of cysteine residues in proteins are briefly discussed: (a) What are the molecular mechanisms involved in dynamic acylation? (b) What are the determinants of the fatty acid specificity and the structural requirements of the acceptor proteins? (c) What are the physiological signals regulating this type of protein modification, and (d) What is the biological role(s) of this reaction with respect to the functioning of specific nervous system proteins? We also present the current experimental obstacles that have to be overcome to fully understand the biology of this dynamic modification. PMID- 7800122 TI - Expression and biological functions of sulfoglucuronyl glycolipids (SGGLs) in the nervous system--a review. AB - Sulfoglucuronyl carbohydrate linked to neolactotetraose reacts with HNK-1 antibody. The HNK-1 carbohydrate epitope is found in two major glycolipids, several glycoproteins and in some proteoglycans of the nervous system. Most of the HNK-1 reactive glycoproteins so far identified are neural cell adhesion molecules and/or are involved in cell-cell interactions. HNK-1 carbohydrate is highly immunogenic. Several HNK-1-like antibodies, including IgM of some patients with plasma cell abnormalities and having peripheral neuropathy, have been described. This article summarizes published work mainly on sulfoglucuronyl glycolipids, SGGLs and covers: structural requirements of the carbohydrate epitope for binding to HNK-1 and human antibodies, expression of the lipids in various neural areas, stage and region specific developmental expression in CNS and PNS, immunocytochemical localization, loss of expression in Purkinje cell abnormality murine mutations, biosynthetic regulation of expression by a single enzyme N-acetylglucosaminyl transferase, identification of receptor-like carbohydrate binding neural proteins (lectins), and perceived role of the carbohydrate in physiological functions. The latter includes role in: pathogenesis of certain peripheral neuropathies, in migration of neural crest cells, as a ligand in cell-cell adhesion/interaction and as a promoter of neurite outgrowth for motor neurons. Multiple expression of HNK-1 carbohydrate in several molecules and in various neural cell types at specific stages of nervous system development has puzzled investigators as to its specific biological function, but this may also suggest its importance in multiple systems during cell differentiation and migration processes. PMID- 7800124 TI - Metabolic turnover of myelin glycerophospholipids. AB - The apparent half life for metabolic turnover of glycerophospholipids in the myelin sheath, as determined by measuring the rate of loss of label in a myelin glycerophospholipid following radioactive precursor injection, varies with the radioactive precursor used, age of animal, and time after injection during which metabolic turnover is studied. Experimental strategies for resolving apparent inconsistencies consequent to these variables are discussed. Illustrative data concerning turnover of phosphatidylcholine (PC) in myelin of rat brain are presented. PC of the myelin membrane exhibits heterogeneity with respect to metabolic turnover rates. There are at least two metabolic pools of PC in myelin, one with a half life of the order of days, and another with a half life of the order of weeks. To a significant extent biphasic turnover is due to differential turnover of individual molecular species (which differ in acyl chain composition). The two predominant molecular species of myelin PC turnover at very different rates (16:0, 18:1 PC turning over several times more rapidly than 18:0, 18:1 PC). Therefore, within the same membrane, individual molecular species of a phospholipid class are metabolized at different rates. Possible mechanisms for differential turnover of molecular species are discussed, as are other factors that may contribute to a multiphasic turnover of glycerophospholipids. PMID- 7800126 TI - Vascular considerations and complications in cranial base surgery. AB - The technical evolution of cranial base surgery has resulted in approaches that allow more radical surgical extirpation of complex cranial base lesions. Our service has extensively applied these cranial base approaches for lesions of the cranial base. A subgroup of 100 patients who had cranial base tumors involving potential manipulation or sacrifice of carotid arteries underwent 20-minute balloon test occlusions coordinated with vascular assessments consisting of a combination of the following: 1) four-vessel cerebral angiogram with compression studies; 2) occlusion transcranial Doppler ultrasonography; 3) occlusion single photon emission computed tomography perfusion studies; and 4) xenon-133 cerebral blood flow studies. Transient neurological deficits associated with balloon test occlusion occurred in 7 of 100 patients (7%). Subsequently, 18 patients underwent permanent carotid occlusion by endovascular detachable balloons. Delayed ischemic complications (> 72 h) occurred in 4 of 18 (22%) patients. Additionally, a number of vascular complications not predicted by the balloon occlusion tests and vascular assessments were experienced. Repeat vascular assessments defined the causes and guided treatment of ischemic patients. Ischemic complications were caused by hemodynamic insufficiency, embolization, vasospasm, radiation vasculopathy, and venous anomaly. Our experience leads us to believe that no vascular assessment exists today that can predict the occurrence of vascular complications accurately. The current enthusiasm for cranial base surgery must be tempered with the sober reality that management of cerebrovascular anatomy and physiology remain significant limitations. Consideration of potential cerebrovascular complications is paramount to successful outcome and implementation of cranial base surgery. PMID- 7800128 TI - Surgical implications of magnetic resonance-enhanced dura. AB - The purpose of this study was to assess tissue changes responsible for dural enhancement of magnetic resonance imaging (MRI) and its clinical implications. A prospective surgical, histopathological, and MRI study was performed in 73 patients with various types of disease, including meningiomas (n = 29), craniofacial tumors with possible direct intracranial extension (n = 21), gliomas and brain metastasis in close proximity to the dura mater (n = 9), and a variety of nonneoplastic processes (n = 14). Contrast-enhanced MRI was obtained within 5 days before surgery and in some cases within 3 days after surgery as well. Histopathological examination of the dural specimens was performed in all 59 patients with neoplasia and in selected patients with nonneoplastic processes. Dural invasion was noted in 18 of 29 meningiomas, 15 of 21 craniofacial neoplasms, 3 of 5 gliomas, and 3 of 4 brain metastases. In these patients invasion was focal and in direct continuity with the tumors. MRI disclosed that dura invaded by the tumor had a break in the continuity of enhancement, or that there was no discernible enhancement. Association between patterns of dural enhancement and tumor invasion of dura was statistically significant (P < 0.001). The thickened-enhanced portion of the dura represented reactive changes. Postoperative enhancement was seen as early as 24 hours after surgery and was shown histologically to be associated with vasodilation and reactive changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800127 TI - Recovery of the sutured facial nerve after removal of acoustic neuroma in patients with neurofibromatosis-2. AB - The authors compared the long-term recovery of sutured facial nerves after the removal of 8 neurofibromatosis-2 (NF2)-associated and 22 non-NF2 acoustic neuromas. The patients were from a series of 270 patients operated on for an acoustic neuroma between 1979 and 1989. The assessment was done with a modified House and Brackmann scale from video recordings. At least some facial movement or tone was achieved (Grade 5 or better) in all but three patients, but in none was the recovery excellent. The facial function, judged by the overall appearance in movement, recovered less in patients with NF2 (P = 0.048); a moderately good recovery (Grade 3 or better) was seen in one patient of eight with NF2, as compared with 13 of 22 with non-NF2. In conclusion, if the tumor cannot be peeled off easily from the facial nerve in patients with NF2, leaving a fragment of tumor behind is preferable to cutting and suturing the facial nerve. PMID- 7800125 TI - Myelination in the developing human brain: biochemical correlates. AB - To delineate the biochemical sequences of myelination in the human brain, we analyzed the protein and lipid composition of white matter in 18 baseline cases ranging in age from midgestation through infancy, the critical period in human myelination when the most rapid changes occur. Three adult cases were used as indices of maturity, and 4 cases with major disorders of CNS myelination (maple syrup urine disease, severe periventricular leukomalacia, idiopathic central hypomyelination, and metachromatic leukodystrophy) were analyzed. Brain samples were obtained < or = 24 hours after death. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high performance thin-layer chromatography were used to separate and identify proteins and polar and neutral lipids in an average of 10 sites/brain; computer-based densitometry was used to quantify polar lipids. Biochemical sequences, as manifested by the appearance of the myelin-associated lipids and myelin-specific proteins, closely followed previously described anatomic sequences both temporally and by region, and were identical in all sites sampled: sphingomyelin was followed simultaneously by cerebrosides, MBP, PLP, and nonhydroxy-sulfatide, followed by hydroxy-sulfatide. The onset and tempo of the expression of individual constituents, however, were quite variable among sites, suggesting a wide differential in vulnerable periods to insult in biochemically specific pathways in early life. Cholesterol ester was transiently elevated during late gestation and early infancy, prior to and around the time of the appearance of cerebrosides, sulfatides, PLP, and MBP. Distinctive lipid and protein abnormalities were detected in idiopathic central hypomyelination and metachromatic leukodystrophy. This study underscores the feasibility of the combined biochemical approaches in pediatric brains and provides guidelines for the assessment of disorders of myelination in early human life. PMID- 7800129 TI - Multimodality management of recurrent adult malignant gliomas: results of a phase II multiagent chemotherapy study and analysis of cytoreductive surgery. AB - Fifty-one adult patients with recurrent malignant gliomas were treated in a Phase II trial of multidrug chemotherapy (6-thioguanine, dibromodulcitol, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 5-fluorouracil, and hydroxyurea). Thirty-one patients underwent radical tumor debulking, before the administration of chemotherapy. Fifty-seven percent of all patients had either an objective radiographic response or stabilization of disease after the institution of therapy. The overall median survival time (MST) was 40 weeks; it was 79 and 33 weeks for anaplastic astrocytoma and glioblastoma patients, respectively. The overall median time to tumor progression (MTP) was 19 weeks--32 weeks for anaplastic astrocytoma patients and 13 weeks for glioblastoma patients. Serious chemotoxicity occurred in 35% of patients without permanent morbidity or mortality. The factors that affected response (including disease stabilization), MTP, and MST were identified through a multivariate statistical analysis. A longer MTP was associated with higher Karnofsky scores, lower grade initial histology, lack of prior chemotherapy, greater degree of myelotoxicity, smaller postoperative tumor volumes, greater extent of surgical resection, and a local versus diffuse recurrence pattern. A longer MST was associated with higher Karnofsky scores, lower grade histology at the time of recurrence, greater degree of myelotoxicity, and lobar versus deep tumor location. Response (including disease stabilization) correlated with higher Karnofsky scores, lower grade histology (initial and current), prior lower grade histology, smaller preoperative tumor volume, longer intervals from the time of initial diagnosis, and absence of prior chemotherapy. These results suggest that, in addition to established prognostic factors such as Karnofsky scores, other factors including prior chemotherapy administration, patterns of tumor recurrence, and tumor location may be important variables to consider in future Phase II-III clinical trials. Of the treatment variables analyzed, greater surgical debulking and smaller postoperative tumor volumes were associated with prolonged MTP but not MST, and greater myelotoxicity had a positive association with all outcomes. The significance of this latter relationship and its relevance to chemotherapy dosing will require further study. Standardization in the design and reporting of clinical trials and the use of computer-assisted tumor volume calculations to assess the extent of surgical resection and the response to therapy are advocated. PMID- 7800130 TI - Arteriovenous malformation draining vein physiology and determinants of transnidal pressure gradients. The Columbia University AVM Study Project. AB - Arteriovenous malformation (AVM) draining vein pressure (DVP) may have an influence on both the natural history of the disease and treatment outcome. The purposes of this study were to assess the relationship between DVP and other clinical and physiological variables and to characterize the transmission of arterial pressure across the AVM nidus. DVP measurements were carried out during elective AVM resection with isoflurane/nitrous oxide anesthesia with arterial carbon dioxide pressure of approximately 30 mm Hg. The gradient between the right atrium and operative measurement site was noted. Pre-excision feeding mean arterial pressure and DVP were measured with a 26-gauge needle simultaneously with systemic mean arterial pressure and central venous pressure (CVP). DVP was tested with systemic mean arterial pressure increased to approximately 20 mm Hg with phenylephrine or CVP increased with a Valsalva maneuver. Finally, preresection and postresection DVP values were compared. Relative to the site of measurement, DVP was 7 +/- 5 mm Hg at a CVP of -4 +/- 5 mm Hg (n = 45). There was no influence of presentation, presence of deep venous drainage, size, location, or prior embolization on DVP. In 19 patients, DVP decreased (8 +/- 4 to 5 +/- 3; P < 0.05) whereas CVP increased from pre- to postresection (-4 +/- 5 to -2 +/- 5; P < 0.05). For the phenylephrine challenge (n = 11), there was no difference (P = 0.84) between the delta DVP (2 +/- 1 mm Hg) and the delta CVP (2 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800131 TI - Magnetic resonance imaging in the evaluation of spinal cord injury without radiographic abnormality in children. AB - Seven children aged birth to 17 years with spinal cord injury without radiographic abnormality (SCIWORA) were studied with magnetic resonance imaging (MRI) between 3 hours and 16 days after the injury. There were six cervical cord injuries and one thoracic cord injury. The MRI findings were divided into two groups: extraneural and neural. The extraneural findings included one case of anterior longitudinal ligament disruption and anterior C6-C7 disc herniation associated with hyperextension; one case of posterior longitudinal ligament disruption and C2-C3 disc herniation associated with lateral flexion; and one case of C6-C7 disc abnormality consistent with increased water content occurring with hyperflexion. These ligament and disc injuries did not correlate with late instability. The neural MRI findings included one case of cord transection with rostral cord stump hemorrhage and one case of hemorrhage involving the majority of the cord's transverse diameter, both associated with permanent complete cord injuries; one case of hemorrhage involving a minor portion of the cord and of the brain stem's transverse diameter associated with a severe partial cord injury but subsequent incomplete improvement; one case of edema without hemorrhage associated with Brown-Sequard syndrome and subsequent incomplete improvement; and three cases of normal cord signal and outline. Two of the latter patients had mild cord injuries that recovered completely. In the third, a child with complete T12 sensorimotor paralysis at presentation, the normal MRI findings predicted the subsequent complete recovery. No extraaxial compressive lesion was demonstrated in these seven children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800132 TI - Intravertebral pressure changes caused by spinal microtrauma. AB - Clinical studies indicate variations in intravertebral pressures in patients with and without low back pain. It is known that not all patients with back pain have abnormal lumbar radiographs and, furthermore, microfractures of the endplate may be one of the causes in the origin of low back pain. Consequently, this study was conducted to determine the interrelationship between microtrauma and intraosseous pressures in the lumbar spine. Miniature pressure transducers were inserted into the vertebral bodies and spinous processes of human cadaver spinal units. Radio opaque medium was injected into the nucleus to fluoroscopically monitor the movement of the fluid from the disc as the preparation was loaded up to the initiation of microtrauma (before reaching the ultimate load-carrying capacity). The onset of injury was evidenced by the microfracture of one of the two endplates and impregnation of the contrast medium into the spongiosa. After relaxation, another cycle of loading was applied by limiting the deflections to the maximum compression sustained under the intact configuration. The load, stiffness, and energy-absorbing capacities were lower (P < 0.05) for the injured specimen compared with the intact configuration. The intraosseous pressures were higher (P < 0.05) in the vertebral body and the spinous process of the vertebra where the endplate exhibited microtrauma in the injured cycle compared with the intact cycle. In contrast, the intraosseous pressures in the vertebral body and the spinous process at the level where the endplate remained intact were not significantly different between the two cycles of loading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800133 TI - Posttraumatic meningitis: bacteriology, hydrocephalus, and outcome. AB - To investigate the conditions that have developed in the treatment of posttraumatic meningitis with the use of new antibiotics, the authors studied cases with this infection retrospectively for a period of 68 months. Among 860 patients with moderate to severe head injuries, 12 (1.39%) sustained this complication. Of these, nine patients (75%) had a demonstrable basilar skull fracture and seven (58.3%) presented obvious rhinorrhea. Of these seven, four (57.1%) were treated conservatively and three (42.8%) finally underwent surgery for dural repair. The infecting agents were Gram-positive cocci (Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus epidermidis, and Streptococcus pneumoniae) in five patients and Gram-negative bacilli in six patients (Escherichia coli in two, Klebsiella pneumoniae in two, and Acinetobacter anitratus in two). In one patient, the culture results were negative. All Gram-negative strains appeared resistant to ampicillin and third generation cephalosporins, but sensitive to imipenem and to the quinolone ciprofloxacin. Gram-positive strains were sensitive to vancomycin. Hydrocephalus finally developed in the two patients who had received intrathecal infusions of amikacin. No other report of the relation of intrathecal infusion of antibiotics and the development of hydrocephalus was found. All patients survived, indicating that, for the present, posttraumatic meningitis is a nonfatal complication of head injury. PMID- 7800134 TI - Organ culture of a glioblastoma from a patient with an unusually long survival. AB - Multicellular tumor spheroids were directly initiated in vitro from the biopsy specimens of a patient who is alive and who has had no neurological changes in 7 years after the gross removal of a glioblastoma. The spheroids were studied alone and in confrontation with aggregates of fetal rat brain tissue. Both in the biopsy and in the tumor spheroids, a very high proportion of cells were proliferating, as flow cytometric deoxyribonucleic acid measurements showed that 40% of the cells in the biopsy specimens and in the tumor spheroids were in the S and G2M phases of the cell cycle. Despite this high proliferation rate, the volume of the spheroids decreased, indicating an even greater cell loss. Light and scanning electron microscopic studies also indicated cell death in the spheroids. This behavior may be related to the long-time survival. PMID- 7800135 TI - Human acoustic neuromas secrete interleukin-6 in cell culture: possible autocrine regulation of cell proliferation. AB - Interleukin-6 (IL-6) secretion by cell cultures of human acoustic neuromas was examined. Secretory rates varied from 0.02 to 5.4 ng/10(5) cells per 4 days, depending on the tumor. The IL-6 immunoreactivity eluted from a Sephadex G-100 column in a major peak corresponding to an M(r) of 30,000 and a lesser peak corresponding to an M(r) of 50,000. Western blot analysis revealed three IL-6 immunoreactive bands with M(r)s corresponding to 53,000, 29,000, and 24,000. Tumor necrosis factor-alpha, interleukin-1-beta, and cholera toxin all stimulated IL-6 secretion. An antisense phosphorothioate oligonucleotide against IL-6 messenger RNA inhibited both [3H]thymidine uptake and IL-6 secretion by acoustic neuroma cells in culture. In addition, [3H]thymidine uptake was inhibited by a specific polyclonal antibody against IL-6. We conclude that human acoustic neuroma cells produce and secrete IL-6, which may act in an autocrine manner to stimulate cellular proliferation. PMID- 7800137 TI - Experimentally-induced autonomic neuropathy: beneficial effect of a topical ACTH4 9 analogue on oculomotor nerve regeneration. AB - Melanocortins, peptides related to corticotropin (ACTH) and melanocyte stimulating hormone, are known to exert beneficial neurotrophic effects in peripheral sensorimotor neuropathies. This has been demonstrated after both systemic and local administration of the peptides. By photographing the rat's pupil under standardized conditions, the authors have previously shown that systemic administration of a synthetic ACTH4-9 analogue can also be beneficial in autonomic neuropathies. The present study demonstrates that topical application of a synthetic ACTH4-9 analogue incorporated in a two-component fibrin glue enhances the speed of recovery of the parasympathetic nerve fibers in the oculomotor nerve after a crush lesion. This may have implications for future use in neurosurgery. PMID- 7800136 TI - T cell-mediated cytotoxicity of human gliomas: a tumor necrosis factor independent mechanism. AB - Cellular immune effector mechanisms are implicated as potential therapies for malignant gliomas. We have examined the potential for anti-CD3-activated human peripheral blood-derived CD4+ and CD8+ T cells to induce lysis of human glioma cell lines in vitro, the mechanism of action of these cells, and the capacity of the glioma to inhibit the effect. We found that activated CD4+ and CD8+ T cell preparations containing less than 5% natural killer cells could induce significant lysis of the glioma cell line U251, as measured by an 18-hour, but not 5-hour, chromium-51 or lactate dehydrogenase release assay. This effect was not reproduced using recombinant tumor necrosis factor or inhibited with antitumor necrosis factor antibody. Anti-lymphocyte functional antigen-1 and anti intercellular adhesion molecule antibodies also did not inhibit the effect. Glioma-derived supernatant could inhibit the proliferation of the T cells but not the cytotoxic effect. Human fetal astrocytes were also susceptible to the cytotoxic effect of the activated T cells. These results indicate that activated T cells can induce glioma cytotoxicity via a mechanism independent of tumor necrosis factor. The therapeutic potential of this effector mechanism will depend on its capacity to deliver these cells or their specific effector molecules to the tumor site or to augment the activity of such cells, which accumulate naturally in gliomas. PMID- 7800138 TI - Combined and three-dimensional rendered multimodal data for planning cranial base surgery: a prospective evaluation. AB - Magnetic resonance (MR), X-ray computed tomography (CT), and angiographic images best depict soft tissue, bone, and blood vessels respectively. No one on its own is sufficient in the preoperative assessment of cranial base lesions. We have developed and evaluated a computational technique for the three-dimensional (3D) combination and display of multimodality images for planning cranial base surgery. This evaluation was prospective and performed in such a way that the results could be quantified. Eight patients (three acoustic neuromas, four subfrontal and suprasellar meningiomas, and one petrous apex meningioma) underwent MR, CT, and MR angiographic investigations. These images were registered with anatomical landmarks rather than an external frame. Two techniques were used to display the resulting combined images: multiple slices in which bone from CT was overlaid on soft tissue from registered MR and pseudo-3D rendered movie sequences showing bone from CT, lesions and optic nerves from MR, and blood vessels from MR angiography. The advantages of the combined displays compared with those of conventional methods of viewing were assessed prospectively by the operating surgeon and by an independent surgeon, and the results were compared with operative findings. The preoperative assessment showed a significant improvement (P < 0.05, sign test) in the depiction of both individual structures (lesion and bone from overlaid slices and lesion and vasculature from 3D-rendered displays) and structural relationships (tumor-bone relationships from overlaid slices and of tumor-vasculature relationships from 3D rendered displays). The operative findings indicated that a more accurate interpretation of this information was possible from the combined images. PMID- 7800139 TI - Cranial base approaches to intracranial aneurysms in the subarachnoid space. AB - The use of cranial base approaches to aneurysm surgery is illustrated by means of patient examples. Over a 9-year period, cranial base approaches were used to expose and treat 38 aneurysms involving the anterior communicating artery complex, proximal internal carotid artery, basilar artery, or vertebral artery. The approaches included orbital osteotomy, orbitozygomatic osteotomy, petrous apicectomy, presigmoid petrosectomy, and extreme lateral transcondylar methods. Complications related to the approaches included one partial ptosis and two cerebrospinal fluid leaks, which resolved with treatment. The technique of three dimensional computed tomographic angiography was useful in delineating the vascular anatomy and its relation to the cranial base structures. This helped the surgeon plan the appropriate approach to the aneurysm. Cranial base approaches, used selectively, can provide improved exposure of deep-seated aneurysms and large or giant aneurysms, while minimizing brain retraction. PMID- 7800140 TI - Aggressive papillary middle ear tumors: a report of two cases with review of the literature. AB - Adenomatous tumors of the middle ear are rare, with only approximately 100 cases reported. A distinct subclass of this tumor demonstrates microscopic papillary architecture and has a propensity to erode the petrous bone and extend intracranially. The term "aggressive papillary middle ear tumor" has recently been proposed to describe this more invasive type of middle ear tumor. Thirty seven cases of aggressive papillary middle ear tumors have been reported. We present two additional cases and discuss the clinical, radiologic, histologic, and operative features of this locally aggressive neoplasm. The tumor affects adults of both sexes. The clinical prodrome is prolonged. Presenting signs and symptoms most often relate to the involvement of cranial nerves V-VIII. Imaging studies reveal large, enhancing, destructive tumors with a generous vascular supply. Intraoperatively, the tumors are bloody, fibrous, and adherent to surrounding structures. Various surgical approaches in combination or in series may be used. Preoperative embolization may be helpful. The role of adjunctive radiation is unclear. Aggressive papillary middle ear tumors are histologically benign tumors with clinically destructive behavior. However, it appears that aggressive surgical management affords prolonged survival with minimal worsening of cranial nerve deficits. PMID- 7800142 TI - Pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroid alone: first case report. AB - We report the first case of pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroids without surgery. A 27-year-old woman had been monitored for chronic headache 13 months after giving birth, associated with amenorrhea and galactorrhea. Cranial magnetic resonance imaging revealed a markedly enlarged pituitary gland with a suprasellar extension; the only biochemical abnormality was a mild hyperprolactinemia. Because of a putative diagnosis of prolactinoma, bromocriptine was prescribed at a dose of 5 mg daily, soon followed by the transitory appearance of menstruation. Two years later, panhypopituitarism was present and was revealed by acute adrenal insufficiency. Magnetic resonance imaging revealed that the pituitary mass was the same as previously described, but hormonal investigation showed evidence of complete hypopituitarism and no hyperprolactinemia. Nuclear antibodies were negative as well as other autoantibodies. Human leukocyte antigen serological Class II typing was DR3/DR4. Lymphocytic hypophysitis was then suspected; in the absence of visual complication and because this patient refused surgery, corticosteroids were attempted at a daily dose of 60 mg of prednisone for 3 months, progressively decreased for the next 6 months. Under this treatment, a gradual recovery of all pituitary hormones was observed and magnetic resonance imaging showed a reduction of two-thirds in pituitary mass. Five months after the end of corticoid treatment, our patient relapsed with panhypopituitarism and an increase of pituitary volume. She underwent steroid treatment, and a biopsy was performed and confirmed the diagnosis of autoimmune hypophysitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800141 TI - Dural cavernous angiomas outside the middle cranial fossa: a report of two cases. AB - Cavernous angiomas of the dura mater are clinically and radiographically distinct from parenchymal cavernous angiomas. In this report, we present two cases of dural cavernous angiomas located outside the middle cranial fossa. The first patient is a 36-year-old woman with two dural cavernous angiomas, including one that enlarged during a 2-year period of observation. The second patient is a 33 year-old man with medically intractable seizures from a dural cavernous angioma of the convexity, which was discovered at autopsy. From our experience and a review of the literature, we have identified two groups of dural cavernous angiomas that differ in incidence, natural history, and surgical management. Most dural cavernous angiomas arise from the middle fossa; in contrast, only 15 cases of dural cavernous angiomas outside the middle fossa have been reported. Those in the middle fossa are more clinically aggressive and more difficult to resect surgically, because they grow toward the cavernous sinus and the parasellar region. Most patients with dural cavernous angiomas outside the middle fossa present with headaches, whereas those patients with dural cavernous angiomas in the middle fossa present with ocular signs, visual field defects, endocrinopathy, and trigeminal symptoms. Radiographically, both of the angiomas resemble meningiomas. Because of their intimate association with the cavernous sinus, surgical resection of middle fossa cavernous angiomas often is incomplete and may require postoperative radiosurgery to control growth. In contrast, angiomas in other locations are easily and successfully resected with little blood loss. The location of dural cavernous angiomas is an important factor in making the surgical decision and in predicting the outcome. PMID- 7800144 TI - Spinal canal stenosis with hypophosphatemic vitamin D-resistant rickets: case report. AB - A 42-year-old woman with sex-linked hypophosphatemic vitamin D-resistant rickets presented with a 6-month history of progressive weakness and numbness in her lower extremities. Radiological studies revealed severe spinal canal stenosis extending from levels T4 to T10. Her symptoms improved markedly after extensive thoracic laminectomies. PMID- 7800143 TI - "Mickey Mouse" aneurysm presenting with cranial bruit: case report. AB - The production of a bruit associated with intracranial aneurysms is very rare. A patient with a bilobed aneurysm of the middle cerebral artery who was otherwise asymptomatic was admitted with both a subjective and an objective bruit. The bruit resolved with elective clipping of the aneurysm. After a thorough review of the literature, a total of 12 cases of proved intracranial aneurysms were found with associated bruit. Five of those were carotid artery aneurysms within the cavernous sinus. Most (67%) of those patients reviewed were admitted with hemorrhage that was present either into the cavernous sinus or in the form of subarachnoid hemorrhage, with the bruit only secondarily noted. A possible explanation for the production of bruits caused by intracranial aneurysms is discussed. We conclude that, although an audible bruit as the presenting symptom of an intracranial aneurysm is quite rare, it deserves serious surgical considerations. PMID- 7800145 TI - Language-activated single-photon emission tomography imaging in the evaluation of language lateralization--evidence from a case of crossed aphasia: case report. AB - We report a right-handed patient who developed a nonfluent aphasia after surgery for a right parietal arteriovenous malformation. Resting brain single-photon emission tomography displayed decreased regional cerebral blood flow only in the right hemisphere, with spared regional cerebral blood flow in the left hemisphere. Single-photon emission tomography performed after a language activation task (Boston Naming Task) showed a consistent area of increased regional cerebral blood flow in the right inferior and posterior frontal lobe, supporting a right hemisphere dominance for language. These results suggest a potential role for this noninvasive study in the evaluation of language lateralization. PMID- 7800146 TI - Brain stem compression secondary to adipose graft prolapse after translabyrinthine craniotomy: case report. AB - Three cases of fat graft prolapse into the cerebellopontine angle with clinical deterioration are presented. These patients had undergone translabyrinthine craniotomy for cerebellopontine angle tumors and had autologous abdominal fat strips placed to obliterate the dural defect and the mastoid cavity. Two patients suffered significant morbidity, and one patient died. Clinical presentation, computed tomographic scan findings, methods of treatment, and avoidance of this complication are discussed. PMID- 7800147 TI - A near-fatal complication of endoscopic third ventriculostomy: case report. AB - The authors treated a 14-year-old girl with posthemorrhagic hydrocephalus and an infected ventriculopleural shunt. She was taken for endoscopic third ventriculostomy with the hope of removing the hardware entirely, but she developed an arrhythmia and hypertension, followed rapidly by complete cardiac arrest. She was resuscitated successfully, made a complete recovery, and subsequently underwent a conventional shunt replacement. This is a newly reported life-threatening complication of neuroendoscopy that must be anticipated by any surgeon undertaking such a procedure. PMID- 7800149 TI - Partial hypoglossal to facial nerve anastomosis for reinnervation of the paralyzed face in patients with lower cranial nerve palsies: technical note. AB - Reanimation of the paralyzed face in patients who have coexisting lower cranial nerve palsies is a difficult management problem. Classic hypoglossal to facial nerve anastomosis may be devastating in these already compromised patients. We describe a technique of partial hypoglossal to facial anastomosis that can preserve hypoglossal nerve function and provide adequate facial reanimation. PMID- 7800148 TI - Fibrin sealing of mucoperichondrial flaps in endonasal-transsphenoidal pituitary surgery: technical note. AB - We describe a simple technique that helps to avoid nasal septum perforations and the related complications after endonasal-transseptal transsphenoidal pituitary surgery. At the end of the Hirsch procedure, the mucoperichondrium is fixed to the septal cartilage with a thin layer of fibrin glue. Two silicone splints are applied to both sides of the septum and left in place for 2 days. The technique is very useful in preventing possible displacement of the mucoperichondrium, which may lead to compression and ischemia of the doubled mucosa between the septal cartilage and the silicone splints. A firm fixing of the margins of a mucoperichondrial laceration to the septal cartilage creates conditions for optimal healing and reduces nasal-packing time and nasal-splinting time. The technique is recommended for all patients with and without mucosal tears and is also recommended for the transsphenoidal reoperations. PMID- 7800150 TI - Flow-directed atrial catheter placement for ventriculoatrial shunts: technical note. AB - The placement of the atrial portion of a ventriculoatrial shunt is occasionally rendered difficult by a tendency of the shunt catheter to pass into the contralateral jugular vein or into a subclavian vein instead of into the atrium. We report a simple flow-directed technique that may resolve this problem. PMID- 7800151 TI - Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study. PMID- 7800152 TI - Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study. PMID- 7800153 TI - Parasellar classification of pituitary adenomas. PMID- 7800154 TI - The piriformis muscle syndrome: a simple diagnostic maneuver. PMID- 7800156 TI - The impact of raising blood glucose on reaction times. AB - Although previous studies have demonstrated enhanced mood and memory in humans following the consumption of glucose drinks, the effect of increasing blood glucose levels on other tasks has not received the same attention. In the present study, inspection time was unaffected by glucose drinks and blood glucose levels. However, increasing blood glucose levels resulted in faster decision times when reaction time was measured. It is concluded that speed of processing is faster when the availability of glucose to the brain is increased. The possibility that the glucose-induced improvements in reaction time reflect an increased synthesis of acetylcholine is discussed. PMID- 7800155 TI - Effects of long-term treatment with the MAO-A inhibitor moclobemide on sleep EEG and nocturnal hormonal secretion in normal men. AB - Sleep EEG, nocturnal penile tumescence (NPT) and nocturnal hormone secretion were studied in four normal males during placebo, under up to 300 mg per day of moclobemide, the short-acting and reversible inhibitor of monoamine oxidase (type A), and after withdrawal. Under moclobemide, REM sleep was slightly suppressed. Drug cessation was followed by REM rebound. In contrast to REM sleep, NPT was not affected by the drug. The nocturnal cortisol concentration was elevated under moclobemide and this effect persisted after withdrawal. No influences on growth hormone, prolactin, testosterone, luteinizing hormone or follicle-stimulating hormone were found. PMID- 7800157 TI - Differences in P3 amplitudes between schizophrenics and healthy controls vary between the different events presented in a guessing task. AB - P3 amplitudes were often found to be reduced in schizophrenics, but in varying degree. We studied in a guessing task whether variations of group differences could even be obtained within the same task, by measuring P3 in the potentials evoked by the three qualitatively different events that occurred in each trial. We hypothesized that such variations were due to variations of subjective task relevance associated with each event. In each trial, a light or a sound was presented. Subjects had to confirm this 'primary event' by a delayed response, and then the current amount of money earned by correct responses was displayed. In the certain condition, the primary event was preceded by the appropriate cue on the screen ('light' or 'sound') whereas in the uncertain condition, the word 'guess' appeared. The task-relevance hypothesis predicted that schizophrenics would have smaller P3s than the control group with the primary event in the uncertain condition, but that the groups would not differ for the P3s evoked by the other events (certain primary event, cue and earnings display in uncertain and certain conditions). Essentially, this predicted pattern of results was obtained, but additional assumptions are needed for the task-relevance hypothesis to account for the precise pattern of results. Analysis of subjects' guessing behavior showed that control subjects' guesses were affected by the outcome of their preceding guesses while schizophrenics' guesses were not. This result provides some additional support for the hypothesis that the guessing task is less relevant to schizophrenics than to control subjects. PMID- 7800158 TI - Does caffeine enhance or merely restore degraded psychomotor performance? PMID- 7800159 TI - Diazepam and sulpiride effects on frequency domain EEG source locations. AB - Effects of an anxiolytic (diazepam; n = 13) and an antipsychotic (sulpiride; n = 6) on the location of EEG model sources in the frequency domain were studied in normal volunteers in 19-channel eyes-closed EEG before and 1, 15, 30, 45 and 60 min after i.v. injections. Ten 2-second epochs from each recording were subjected to the fast Fourier transformation (FFT) Dipole Approximation which results in a single-source (in terms of phase angle) potential distribution map for each frequency point. Three-dimensional model dipole sources were fitted into the maps. Differences in source location before and after injection were computed, and differences between drugs were evaluated. The source location in the beta band shifted significantly more towards superior and anterior areas after diazepam than sulpiride, most prominently in the first minute after injection; during this time, conventional beta band power was significantly increased after diazepam versus sulpiride at all recording sites. The results demonstrate that the FFT dipole approximation adds direct 3-dimensional topographical information to power spectral results in pharmaco-EEG. PMID- 7800160 TI - Effects of cocaine on P3B in cocaine abusers. AB - Little is known about the effects of cocaine on cognitive tasks. Event-related potentials (ERP) were recorded in 7 cocaine abusers during the performance of the auditory oddball task before and after the intravenous injections of saline and cocaine (60-80 mg). The P3B and slow wave components of the ERP were significantly larger 60-210 min after the cocaine than after the placebo injection. The results suggest that cocaine abusers have difficulty in maintaining optimal stimulus processing during extended testing. Cocaine blocks this decrement in stimulus processing. PMID- 7800161 TI - Auditory information processing in sleep: habituation to repetitive stimuli. AB - Habituation to evoked responses is obvious in waking but still controversial in sleep. Single-response analysis proves short-term habituation of auditory evoked potentials in stage 2 NREM sleep. The data are discussed referring to the two system hypothesis of sensory processing in sleep and to DC instability and sleep maintenance mechanisms in stage 2 NREM. It is suggested that information processing might continue in sleep. PMID- 7800162 TI - Nonconvulsive status epilepticus as a cause of confusion in later life: a report of 5 cases. AB - Five patients (4 women, 1 man) presented with an acute confusional episode for the first time between the ages of 53 and 76. Their EEGs showed generalized paroxysmal activity indicating a diagnosis of nonconvulsive generalized status epilepticus (absence status). Two patients had tonic-clonic seizures just before the onset of the status, but none had a history of chronic epilepsy. Three patients had long-standing psychiatric disorders. Treatment with psychotropic drugs and medical illness (vascular disease, metabolic derangement) may have acted as precipitating factors for the status epilepticus in all patients. The diagnosis was never made on admission, since psychiatric history and ictal behavioral manifestations often raised intriguing problems of differential diagnosis. In all cases, only icta; EEG could provide a correct diagnostic assessment. PMID- 7800163 TI - Increase in serotonin 1A receptors in the dentate gyrus as revealed by autoradiographic analysis following repeated electroconvulsive shock but not imipramine treatment. AB - The effects of repeated treatment with electroconvulsive shock (ECS) and imipramine on [3H]8-OH-DPAT binding to serotonin1A (5-HT1A) receptors in the rat brain were studied by quantitative autoradiographic analysis. A large number of binding sites for [3H]8-OH-DPAT were observed in the hippocampus, especially the dentate gyrus, CA1+CA2 field, dorsal raphe nucleus and septum. Repeated treatment with ECS, but not repeated imipramine treatment, significantly increased [3H]8-OH DPAT binding sites in the dentate gyrus. These results suggest that the increase in [3H]8-OH-DPAT binding sites in the dentate gyrus may be important in ECS therapy for depressive illness. PMID- 7800164 TI - Psychoimmune investigation in obsessive-compulsive disorder: assays of plasma transferrin, IL-2 and IL-6 receptor, and IL-1 beta and IL-6 concentrations. AB - This study was carried out to investigate the immune function in obsessive compulsive disorder (OCD). Plasma levels of interleukin (IL)-1 beta, IL-6, soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin receptor (TfR), and baseline plasma cortisol levels were measured in 19 OCD patients and 19 normal controls. No significant differences in any of the above immune variables were found between subjects with OCD and normal controls. There was a significant positive correlation between IL-6 or sIL-6R concentrations and severity of compulsive--but not obsessive--symptoms. In subjects with OCD, there was a significant negative relationship between sIL-2R concentrations and plasma cortisol values. In subjects with OCD and in the study group as a whole, there were significant positive relationships between sIL-2R and TfR concentrations. PMID- 7800165 TI - Seasonal variation in the dexamethasone suppression test: a longitudinal study in chronic schizophrenics and in healthy subjects. AB - To evaluate seasonal influences on the dexamethasone suppression test (DST), cortisol and melatonin responses to dexamethasone were assessed in drug-treated chronic schizophrenics and in drug-free healthy volunteers in different seasons of the year, according to a longitudinal study design. In schizophrenic patients, there was a greater rate of cortisol non-suppression to DST in February as compared to November and May (chi 2 = 4.5, p = 0.03) with no significant differences in pre- and post-dexamethasone plasma cortisol levels. In healthy volunteers, in contrast, no seasonal variation in DST results was observed. Moreover, dexamethasone administration did not significantly affect morning plasma melatonin levels in either patients or healthy controls. These findings suggest that seasonality may be of critical importance in evaluating DST results in schizophrenic patients, but not in healthy subjects. PMID- 7800166 TI - Effect of an antidiencephalon immune serum on pain and sleep in primary fibromyalgia. AB - The results of a double-blind, randomized, therapeutical trial with SER282, an antidiencephalon immune serum (Serolab, Lausanne, Switzerland), in 36 women, aged 24-56 years, with primary fibromyalgia are presented. Treatment was ambulatory and consisted of either SER282 (20 mg/ml) or amitryptiline (AMI, 50 mg) or placebo (PL) over an 8-week treatment course. Clinical and sleep EEG polygraphic data were obtained at baseline and after 4 and/or 8 weeks of therapy. Compared to an important PL response and moderate analgesia with AMI, pain and associated symptoms improved moderately with SER282. In contrast, polysomnographic recordings showed that SER282 tended to promote stage 4 sleep, while AMI and PL had few--if any--effect on sleep. These results are discussed together with the clinical characteristics of the patients and the relations between pain, associated symptoms, and sleep parameters in our patient population. PMID- 7800168 TI - Subjective assessment of sleep: statistical analysis in a population of healthy subjects. AB - A principal components analysis was carried out on subjective data obtained from the sleep questionnaire systematically used in our laboratory on the morning following a polysomnographic recording. This technique, based on 70 healthy subjects, revealed three principal axes which explore the questionnaire. The first axis reflects the subjective evaluation of the quality of sleep. The second underlines the importance of dreams and of the brief waking periods which immediately follow. Finally, the third axis brings out the subjective assessment of sleep efficiency. The third axis was the most ambiguous and the only one to show a gender difference. Women tend to better estimate general sleep events, while men tend to evaluate better the more circumstantial events. Finally, given the results, it would be interesting to apply a similar analysis to populations presenting sleep disorders in order to establish the presence of an eventual pattern specific to the disorder. PMID- 7800167 TI - Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms. AB - Plasma magnesium levels were tested in a group of 155 psychiatric in-patients with a variety of diagnoses and were correlated with the severity of their symptoms. We hypothesized that lower Mg levels would correlate with a higher degree of anxiety, tiredness and other symptoms characteristic of Mg deficiency. No such correlations were observed. However, Mg levels varied widely, with 22.4% below, and 10.4% above the normal range. There was a strong association for more disturbed and excitable patients to have abnormal (either high or low) levels. We speculate that more disturbed patients might have some abnormality of Mg metabolism with possible therapeutic implications. PMID- 7800169 TI - The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline. AB - Three hundred in- and outpatients suffering from depressive disorder, as diagnosed using DSM-III criteria were treated for 6 weeks under double-blind conditions in a multicenter controlled study of tianeptine vs. amitriptyline. Both groups presented steady improvement of depressive syndrome from day 7 up to the end of the treatment, as shown by all evaluation scales: HDRS, SAD, CGI. Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements. In addition to the improvement of mood, the tianeptine-treated patients presented less somatic complaints and side effects when compared to the reference antidepressant. These results confirm previous findings that tianeptine is an effective antidepressant with a lower side effect profile than amitriptyline. PMID- 7800170 TI - Orthostatic challenge during neuroleptic test dose: a possible predictor of short term outcome. AB - Cardiovascular measurements were used as indicators of autonomic arousal during an orthostatic challenge test without medication and after a test dose of 150 mg perazine in 20 acute schizophrenic patients. Unmedicated schizophrenics showed elevated heart rates and elevated systolic and diastolic blood pressure in comparison to healthy volunteers. After a test dose of 150 mg perazine, responders (using BPRS outcome criteria after 23 days) showed a pronounced orthostatic heart rate reaction in comparison to nonresponders. Results are discussed in relation to arousal theories and central dopaminergic activity in schizophrenia. PMID- 7800171 TI - Advanced trauma life support: is it adequate stand-alone training for military medicine? AB - Advanced Trauma Life Support (ATLS) is a 2-day course on handling the acutely injured patient. It has been developed by and is directed by the American College of Surgeons, and teaches a systematic approach to the care of the injured patient. It is relied upon as a teaching tool throughout the active and reserve military medical departments. This article will review its strengths and weaknesses, and will show that it is not an adequate "stand-alone" training tool. ATLS does not address the combat casualty, nor the combat scenario. Special courses must be utilized to train military medical providers for the conflicts and casualties of the future. PMID- 7800172 TI - The battle for Hue: casualty and disease rates during urban warfare. AB - Renewed nationalism with the ending of the Cold War has precipitated numerous conflicts between regions or countries that were formerly united. Hostilities between some ethnic and nationalistic factions have reached the point where regional security is threatened and United Nations-sanctioned military operations may be required. Because some U.N. operations could require the forcible removal of an entrenched faction from an urban setting, the present investigation seeks to determine the levels of medical casualties that might be sustained during urban warfare. Casualty rates and illness incidence were examined for U.S. Marine forces participating in the retaking of the city of Hue during the Tet offensive in 1968. The casualty rates were analyzed for different phases of the urban assault and contrasted with a different period of the Vietnam Conflict, and with the high intensity battle for Okinawa during World War II. Rates of casualties during the retaking of Hue were highest during the two phases of the operation that required close-quarter fighting. The house-to-house fighting south of the river yielded a wounded rate of 37.9 per 1,000 strength per day, while the fighting in the inner city yielded a rate of 44.4. Rate of wounded during the "mopping-up" phase was 5.8. The rate of illness incidence was stable over the month-long operation and showed no concomitant increase with battle intensity." PMID- 7800173 TI - Screening alcohol abuse potential among Army reservists with the Short Michigan Alcoholism Screening Test. AB - The Short Michigan Alcoholism Screening Test was psychometrically useful in screening a sample of 560 reservists from a midwest general hospital unit. The most conservative estimate of alcohol abuse potential was 11.3%, with possibly 6.6% having symptoms of alcohol dependence. Comparisons with active duty military, Army, and civilian samples suggest that prevalence of abuse in the Reserve sample is similar to that of the combined military, but lower than that of the Army. Future research and policy choices are highlighted. PMID- 7800174 TI - Adapting the Ohmeda UPAC draw-over vaporizer for use in the modern operating room. AB - Until recently, the use of draw-over anesthesia (DA) for elective cases has been prohibited in American military hospitals. The reasons cited for this have included the possibility of increased patient risk and the delivery of a second level of care. In this article, the authors outline a method of employing DA so as to bring its use up to the safety level of the modern operating room. This allows for the clinical training of those military anesthesia care providers who may find themselves deployed with highly mobile surgical units whose missions demand this technique of anesthesia. PMID- 7800175 TI - Psychiatric stigma in the military. AB - There is potential for the stigma of mental health care to directly affect an active duty member's career. The authors are aware of cases in which fear of adverse career consequences has led service members to avoid needed mental health care. In order to investigate the legitimacy of this fear, the authors surveyed 252 USN and USMC commanding and executive officers concerning their attitudes about service members who had received mental health and other services; 138 responded. Overall the responses were neutral and there were relatively few negative evaluations of service members who had received services. Military health care providers should take an active role in diminishing the stigma of mental illness, and in allaying fears of adverse career consequences for seeking care. PMID- 7800176 TI - Dermatological manifestations in a tropical training environment: emphasis for the general medical officer. AB - Cutaneous disease in the tropical training environment will be of concern for the medical officer assigned to ensure the health of soldiers participating in training. A review of all "sick calls" recorded during deployment to the Jungle Operations Training Center at Fort Sherman, Panama showed that 50% of the medical complaints were dermatologically related. This should emphasize the need for medical officers to have significant dermatologic knowledge and appropriate supplies. PMID- 7800177 TI - Model program for interdisciplinary care of exceptional family members at a large USAF Medical Center. AB - Because we have a large population of exceptional family members, in November 1990 our pediatric department developed a comprehensive interdisciplinary team to manage these complicated cases. The goals of this team were similar to those defined by the 1985 USAF Exceptional Family Member Program, Regulation 160-38. We describe the organization, membership, and categories of patients served, and benefits of this form of comprehensive care including identifying and coordinating supportive community services. By reporting our experience, we hope other military medical centers will benefit from this interdisciplinary approach. PMID- 7800178 TI - Adjustment disorder of conscripts as a military phobia. AB - Conscription entails many adjustment difficulties for the young soldier. When anxiety is sufficiently severe to impair performance and make discharge a possibility, a brief course of cognitive-behavioral therapy can rapidly restore the soldier to full functioning. This article explains the theoretical basis for such an approach, and describes three cases. PMID- 7800180 TI - Paddling permanent white water: managing within the paradigm shifts in military medicine. AB - The challenges of managing military medicine over the last three decades have been complicated by rapidly changing priorities and redirections. Inspired by Kuhn's theory of "paradigm shifts," we can identify five distinct paradigms and four paradigm shifts that have dominated military medicine over the last 25 years. These shifts began in the early 1970s when military medicine was forced to make a transition from a focus on combat casualty care to the problems of becoming an all-volunteer force. These paradigm shifts continue in the form of the current challenges of simultaneously embracing new cost-conscious forms of health care delivery while downsizing the force. Each of the shifts has been characterized by a lack of anticipation and the onset of crisis. The present challenges faced by military medical leadership are not necessarily unprecedented; prescience in regard to inevitable future shifts could reduce turmoil and enhance adaptation. PMID- 7800179 TI - Predictors of basic infantry training success. AB - Because of shrinking resources, the United States military will be forced to carry out its mission in the future with maximum efficiency. Medical problems reduce the efficiency of the training of soldiers. Our project documents the medical problems that occurred in infantry basic trainees and tests easily obtainable information for its ability to predict the impact of medical problems on each trainee. The study involved 649 trainees undergoing a 13-week cycle of basic and advanced infantry training in one of three companies at the United States Army Infantry Training Center, Fort Benning, Georgia. The most common reason for sick call attendance among this group of trainees was upper respiratory infection. While medical illnesses were frequently seen, they did not cause a great deal of lost training time. Training injuries such as foot and lower leg overuse syndromes and patellofemoral knee pain were the primary causes of time lost. The average trainee made 1.58 +/- 1.61 visits to sick call during the cycle, with a total of 4.53 +/- 8.49 days of training time limited by profile. However, many trainees made no sick call visits and the majority of trainees lost no time due to medical problems. The strongest predictors of medical impact on training were a history of cigarette smoking and the initial performance of the trainee on the three events of the Army Physical Fitness Test. Based on the results of this study, we recommend that the military consider cigarette smoking as a negative factor in the selection of recruits and consider that recruits be required to meet some standard of fitness prior to induction. PMID- 7800181 TI - Bilateral chylothorax following thymectomy: resolution following unilateral drainage. AB - Chylothorax is a rare complication of thymectomy. Following thymectomy for myasthenia gravis, our patient developed bilateral chylous pleural effusions. The presence of a "mediastinal window" allowed adequate drainage with a unilateral chest tube. PMID- 7800182 TI - Continuous intra-arterial blood gas monitoring. A clinical experience. AB - Miniaturized sensors, based upon the principles of optical fluorescence, can measure in vivo the pH, pCO2 value and pO2 value of blood. In this report we studied continuous intra-arterial blood gas monitoring in 27 patients undergoing cardiac surgery (no. 16 coronary artery by-pass grafting, no. 2 valvular surgery) and major vascular surgery (no. 9 abdominal aortic aneurysms). Total duration of continuous intra-arterial blood gas monitoring was 677 hours, with a ratio of 25.0 +/- 14.8 hours/patient (range 4-96 hours). The in vitro values of pH, pCO2 and pO2 were compared to simultaneous records from the fiberoptic sensor for each of the 283 arterial blood gas samples obtained, by means of linear regression and Bland-Altman method, in order to test the correlation and the agreement between the two methods of measuring. For pH average bias was -0.023 and intersensor precision was 0.028, with a strong correlation (R = 0.92; p < 0.001) and agreement. For pCO2 the average bias was 0.91 and the inter-sensor precision was 2.65, with a slight decrease in correlation (R = 0.89; p < 0.001) and agreement. For pO2 average bias was -2.69 and the intersensor precision was 12.16, with a strong correlation (R = 0.97; p < 0.001) and agreement. In addition, we tested the reliability of the system for values of pO2 above 100 mmHg and we found a strong correlation (R = 0.96; p20.001) and agreement even for these clinical conditions, largely out of physiologic parameters. This study demonstrates the feasibility and reliability of continuous intra-arterial three-component PB 3300 (Puritan Bennett) blood gas monitoring. PMID- 7800183 TI - [Effects of age, body weight, and ventilatory pattern on the difference between arterial and end-tidal PCO2]. AB - OBJECTIVE: To evaluate the effects of physiological ventilatory patterns on P(a ET)CO2 gradient and on the alveolar dead space production during controlled mechanical ventilation. DESIGN: Prospective and experimental comparison among three different ventilatory settings in three different groups of subjects. SETTING: General surgery's operating-theatre in university hospital. PATIENTS: Twenty-eight patients subdivided randomly in 3 groups differing for ventilatory setting. I group: constant tidal volume (VC = 8 ml.kg-1) and 3 different respiratory frequencies (f = 10, 12 and 14 breaths.min-1); II group: constant ventilation (112 ml.kg-1) but VC and f modified in three different ways; III group: inspiratory volume was set to give an end-tidal PCO2 (PETCO2) of about 35 mmHg. The cases were subdivided, on the basis of P(a-ET)CO2 distribution, in three groups: group with values larger than mean plus 1 standard deviation, group with values between +/- 1 standard deviation and group with values lower than mean minus 1 standard deviation. Moreover in two homogeneous groups for age. INTERVENTIONS: General surgery but not important because measures were performed before surgical manoeuvres. MEASUREMENTS AND MAIN RESULTS: Anthropometrical data (age and body weight), PaCO2, PETCO2, heart rate, invasive arterial pressure, ventilatory parameters and airway pressure were collected for every subject and ventilatory setting; arterial to end-tidal difference P(a-ET)CO2 and P(a ET)CO2.PaCO2(-1) were calculated during data analysis. The P(a-ETFCO2 and P(a ET)CO2.PaCO2(-1) values were not significantly different among the three different ventilatory patterns both in the first and in the second group. P(a ET)CO2 values were significantly correlated with age, body weight and airway pressure. These parameters were correlated significantly also with P(a ET)CO2.PaCO2(-1) values. CONCLUSIONS: Ventilatory setting, used in a normal physiological range, don't affect P(a-ET)CO2 difference during mechanical ventilation. Age, body weight and airway pressure of the patient must be considered to obtain a correct value of PaCO2 by the measure of PETCO2. PMID- 7800184 TI - [Perioperative blood gas analysis in 100 patients in spontaneous respiration treated with ND-YAG laser for endoluminal tracheo-bronchial neoplasms]. AB - OBJECTIVE: To determine the reliability on spontaneous ventilation of small continuously associated doses of ketamine and propofol during yag-laser therapy for upper airways neoplastic obstructions. DESIGN: Prospective description of blood gas analysis variation throughout the intervention and in the early postoperative period. SETTING: Operating theatre and postoperative Intensive Care Unit of the National Institute for Cancer Research. PATIENTS: A hundred consecutive cancer patients referred to our Institution for upper airways tumoral progressive obstruction. INTERVENTION: Yag-laser firing. MEASUREMENTS AND MAIN RESULTS: Pre-intra and postoperative blood gas analysis, BP, HR, Sat O2 have been registered every 10'. Mean intraoperative pCO2 rose to 47.3 mmHg (30-60), but within 2 to 3.20 hrs returned close to preoperative value (38.3 mmHg) allowing early patient discharge. CONCLUSIONS: The i.v. association of 0.7-1.0 mg/kg Ketamine and 1 mg/kg propofol, followed by 5 micrograms/kg/h and 3 mg/kg/h respectively, turned out to be satisfactory for both patients and anaesthetists in terms of anaesthesia and spontaneous breathing maintenance during yag-laser firing for obstructive upper airways cancer patients. PMID- 7800185 TI - [Difference between arterial and end-tidal carbon dioxide tension during surgery of lumbar herniated disk in general anesthesia]. AB - OBJECTIVE: To determine the correlation of PaCO2 and ETCO2 during operations for lumbar disk herniation in prone position: the influence of position and deliberate hypotension. DESIGN: Prospective, to compare PaCO2, ETCO2, pH, SBE, Pa max, in a group of 10 patients undergoing elective intervention for lumbar disk herniation in prone position and in a control group of 10 patients undergoing interventions for elective non traumatologic orthopaedic surgery of the lower limbs in supine position. SETTING: Orthopaedic department of a non teaching hospital. MEASUREMENTS AND MAIN RESULTS: The results for the patients of the supine group were: mean PaCO2 35.26 mmHg (SD 3.045), mean P(a-ET)CO2 3.46 mmHg (SD 1.898), mean pH 7.433 (SD 0.044), mean SBE - 1.16 (SD 1.718), mean Pa max 122.5 mmHg (SD 17.989). In the prone group: mean PaCO2 30.3 mmHg (SD 5.819), mean P(a-ET)CO2 1.4 mmHg (SD 4.445), mean pH 7.430 (SD 0.052), mean SBE-3.93 (SD 3.255), mean Pa max 100.3 (SD 10.945). The difference was significant (p < 0.05) for pH, PaCO2, SBE; in the prone group the variability of P(a-ET)CO2 was greater and the values related with SBE. CONCLUSIONS: ETCO2 is a useful monitoring for PaCO2 in the situation evaluated but the accuracy of the correlation with PaCO2 is lesser than during standard surgical techniques, the metabolic acidosis observed is probably related to the effects of the peculiar position and the anaesthetic technique. PMID- 7800187 TI - [Sudden infant death syndrome (SIDS): risk conditions and intervention strategies]. AB - The term SIDS describes the unexpected and unexplained death of an apparently well infant. After congenital anomalies, SIDS is the most common cause of infant death in the industrial countries and it is the leading cause of death among infants older than 1 month. Descriptive epidemiological studies have shown a winter excess of cases and a peak of age distribution at about 3 months of age. Although many theories have been proposed to explain the etiology (i.e. fatal toxaemia, autonomic dysfunction, abnormalities of respiratory or cardiovascular control), an underlying cause for SIDS has not been identified. There are, however, a number of factors consistently associated with an elevated risk, the strongest of which are maternal smoking or exposure to substances of abuse during pregnancy, overheating and overinsulation, artificial feeding and prone sleeping position. A fall in the rate of the SIDS can be reasonably expected from changes in these risk factors, from home monitoring of infants suffering a near-SIDS episode and of siblings of SIDS victims, and from parental education programmes. PMID- 7800186 TI - [Sedation with benzodiazepine in ophthalmologic surgery: comparative study of diazepam and midazolam]. AB - INTRODUCTION: To evaluate the effect of giving diazepam and midazolam, respectively 0.1 mg/kg and 0.03 mg/kg on: PAS, PAD, PAM, HR, SaO2 and sedation level at 10, 30, and 50 minutes from injection. These drugs were utilized as sedatives during retrobulbar blockade as anaesthetics technique in cataract surgery. Randomized double blind in operating room for opthalmic surgery in general hospital. MATERIALS AND METHODS: 40 patients (ASA II, III) with mean age 78 +/- 7 divided in two groups with homogeneous morphological and clinic parameters, scheduled for elective cataract surgery. During retrobulbar blockade as anaesthetic technique the patients received diazepam and midazolam in equipotent quantities. Serial measurements of PAS, PAD, PAM, HR, SaO2 and sedation level. RESULTS: Both drugs proved significantly depressant on PAS, PAD, PAM, HR, SaO2. Midazolam proved more depressant than diazepam on SaO2 at 10 minutes from injection; the depression was the same for both drugs at 50 minutes. Sedation level seems higher for midazolam group than diazepam at 10 and 30 minutes, approximately the same for both groups at 50 minutes. CONCLUSIONS: Our results agree with there in the literature. The data show that midazolam is more depressant than diazepam on SaO2 at 10 minutes from injection and the necessity of a controlled "tritation" in small doses for intravenous use of midazolam. PMID- 7800189 TI - [Multiple organ failure (MOF) in tertian malaria. Report of a clinical case]. AB - The authors describe a malignant malaria clinic case complicated by shock, disseminated intravascular coagulation (DIC) and multiple organ failure (renal, heart, lung failure): MOF. Early diagnosis and suitable therapy, with multiple organ failure intensive care allowed a good patient outcome. PMID- 7800190 TI - [Travel medicine in the era of the HIV pandemic]. PMID- 7800188 TI - [Severe pulmonary gas embolism caused by intraoperative administration of hydrogen peroxide]. AB - We report the case of a 3 year old boy who developed cardiac arrest during general anesthesia, immediately after the subcutaneous administration of hydrogen peroxide solution. Massive pulmonary embolization was hypothesized as the postoperative ECG showed an acute heart strain. However the occurrence of transient anisocoria, associated with a paresis affecting the left arm, remained unexplained. Since brain MR did not reveal any pathological data, a direct toxicity of hydrogen peroxide on a limited area of the CNS could be assumed. PMID- 7800192 TI - [Blood prolactin patterns in hepatic cirrhosis]. AB - Variations in PRL secretion were observed during chronic hepatic disorders. The aim of our study was to evaluate the behaviour of PRL in patients affected by hepatic cirrhosis. 6 patients (4 males and 2 females) were studied and matched with a group of healthy controls. In all subjects PRL values were evaluated in basal conditions and after TRH stimulation. The results obtained showed higher basal levels of PRL, together with higher and more prolonged TRH responses in patients with hepatopathies than in controls (p < 0.01). These abnormalities in PRL secretion during hepatic cirrhosis could be due to alterations of neurotransmitters at central level. PMID- 7800191 TI - [Incidence and prevalence of anti-HVC antibodies and HBV markers in patients undergoing extracorporeal hemodialysis]. AB - OBJECT: To assess the prevalence and the incidence of the anti-HCV and HBV markers in extracorporeal dialysis patients. METHOD: From 1990 to 1993, every six months, anti-HCV and anti-HBV markers were determined in 88 dialyzed patients, in 24 health workers from the Nephrology and Dialysis Departments and checked with 4143 blood donors. ALT values were also checked monthly. RESULTS: A 13.6 prevalence of anti-HCV was found while no new anti-HCV case was seen in the three year observation period. Data referring to HBV infection were affected by vaccination. Statistical survey has shown a significant relation between anti-HCV and blood transfusions and between anti-HBV infection and duration of dialysis. The incidence of HCV infection was 4.1% among health workers who were all HBV vaccinated in the year before the research. COMMENT: We strongly recommend the observance of such rules as hygiene and prophylaxis, disinfection, sterilization and the use of disposable material. Also, a reduction of the number of transfusions seems to cut down the incidence of hematic infections. PMID- 7800193 TI - [Differential diagnosis of pathological and pseudo-pathological shoulder. Clinico ultrasonographic findings]. AB - Clinical examination for rotator cuff tears is rarely conclusive and very difficult is the differential diagnosis with lesions of the axillary nerve. In a little hospital we chose to use first non invasive and cheaper tools for this diagnosis. 24 patients were first evaluated by a physiatric MD, and radiological and ultrasound studies were then performed. Ultrasonography (US) was done with a high frequency probe (7.5 MHz). More than 85% of our patients had, in this way a quick, cheap and non invasive diagnosis, and moreover a quick rehabilitation treatment. Only 3 patients were later studied invasively by arthrography or electromyography with needle, their treatment started later. In 3 patients US demonstrates a normal rotator cuff, and so a diagnosis of nervous lesion. Four patients had a complete large tear of the rotator cuff. In 14 patients US shows small or partial tear. Our non invasive diagnosis was quick, cheap and therapy started earlier with better final results. PMID- 7800194 TI - [Multidimensional diagnosis in general medicine. Comparative study of the use of various instruments]. AB - This study was performed to test three instruments for functional status assessment in General Practice: the Dartmouth Coop Charts (COOP Charts), the Functional Status Questionnaire (FSQ) and the Duke University Health Profile (DUHP). All the instruments covered a score of functional aspects in physical, mental and social areas, providing a multidimensional measure of health status. We used these three instruments, validated by international studies, to acquire information concerning their feasibility and acceptability among patients from rural communities needing primary care and to test their validity in differentiating between patient subgroups. The COOP Charts, the FSQ and the DUHP were administered by physicians respectively to 98, 100 and 97 patients, waiting for a visit in the ambulatories of their General Practitioner. Answers relating to each instrument were analyzed according to sex, age and education of patients. All the instruments seemed to be feasible and acceptable, but only the COOP Charts and the FSQ were able to discriminate between different sex, age and scolarity groups. Taking into account the need to elaborate answers according to a formula when using the FSQ, we concluded that the best instrument for General Practice to provide a multidimensional measure of health status seems to be the COOP Charts. PMID- 7800195 TI - [Gastric endoscopic assessment after treatment with orally administered ketoprofen lysine salt (80 mg granular sachet). Controlled study vs placebo]. AB - In this study, a new oral granular formulation of ketoprofen lysine salt, a non steroidal antiinflammatory drug (NSAID) derived from propionic acid, and placebo, were compared for their local effect on the gastric mucosa of healthy, human volunteers. The study was carried out with a double-blind, randomized, parallel group, design. 10 healthy volunteers were administered one sachet containing 80 mg of ketoprofen lysine salt and 10 volunteers with placebo. The subjects were gastroscoped at baseline and following 10 days drug administration; tolerability was assessed by analysis of the hematology and biochemistry laboratory results, the adverse reaction reports and by the Investigator's and subject's global assessment at the final visit. No symptoms of gastric intolerance were referred in both groups. No statistically significant differences were found between treatments in laboratory results and in final post-treatment tolerability evaluation (Mann-Whitney's test U, Phi and Cramer tests). PMID- 7800196 TI - [Diabetes and prevention: which solution? Trying to solve the type I problem (review of the literature)]. PMID- 7800197 TI - [Celiac disease (familial) associated with sarcoidosis. Clinical case and review of the literature]. AB - The authors report a case of a 42 year-old patient, female, already suffering in 1990 from pulmonary sarcoidosis at 0 radiological stage, together with uveitis and relapsing erythema nodosum, with dyspepsia and weight loss which benefited from corticosteroidal therapy, repeatedly applied at the relapses of Erythema Nodosum. This therapy induced clinical recovery and marked weight gain. After 3 years (in 1993), the appearance of chronic diarrhoea, weight loss, oedemas of the lower limbs and altered laboratory findings which suggested malabsorbtive syndrome, made us verify with clinical-instrumental examinations (serum AGA IgA and IgG, Xilose test, perendoscopic jejunal biopsy) the diagnosis of fully clinically expressed adult coeliac disease. The screening of close relatives, showed that the patient's brother, HLA like (HLA A1-B8), was suffering from a less expressive coeliac disease. After a wide review of the literature, authors emphasize particular aspects of both diseases, reporting clinical manifestations, possible morbid linkage and prognostic factors. They underline epidemiological, pathogenetic and genetic/immunological similarity. bound to support a possible non-causal linkage of the diseases, even within the family. The authors think this linkage to be underestimated, because it is not often searched for on identified. PMID- 7800198 TI - [Exudative pericarditis with pleural plaques caused by exposure to asbestos, resolved with steroidal treatment]. AB - We report a case of a 73-year old railwayman with an asymptomatic large pericardial effusion diagnosed by a routine echocardiogram. By clinical and laboratory tests we excluded an immune, infectious, tuberculous and neoplastic origin of the pericardial effusion. A computed tomography scan of the thorax showed left pleural plaques. Pleural and pericardial biopsies showed fibrohyaline plaques and diffuse aspecific, chronic inflammation consistent with asbestos exposure. By using steroid treatment there was no further evidence of pericardial inflammation or pericardial effusion at 8 month follow-up. Steroid drugs are therefore suggested as a first choice treatment in patients with pleuropericardial effusion as well as chronic asbestos exposure. PMID- 7800199 TI - Regulatory functions of protein kinase C isoenzymes in glomerular mesangial cells. PMID- 7800200 TI - Cell adhesion molecules and inflammatory renal diseases. PMID- 7800201 TI - Lipoprotein(a) in renal patients: is it a key factor in the high cardiovascular mortality? PMID- 7800202 TI - Nephropathy and coronary death--the fatal twins in diabetes mellitus. AB - In summary, the decreased concentration of heparan sulphate within the extracellular matrix of patients with insulin-dependent diabetes mellitus is caused by a combination of genetic factors and poor metabolic control. Decreased concentrations of heparan sulphate are seen in patients with diabetes mellitus and proteinuria and this might be the explanation for the proteinuria as well as the expansion of the mesangium and the intimal dysfunction, including increased permeability of the vessel wall to macromolecules, which is present in such patients. Thus, the effective remodelling of extracellular matrix might explain coincidence of proteinuria, decline in renal function and premature atherosclerosis in patients with diabetes mellitus. PMID- 7800203 TI - Observations in a Saudi-Arabian dialysis population over a 13-year period. AB - In contrast to Europe and the USA, data concerning dialysis treatment in Middle Eastern countries like Saudi Arabia are lacking. We therefore studied 325 patients (150 females and 175 males) in one dialysis centre over a 13-year period. The number of primary renal diseases of uncertain aetiology and of pyelo/interstital nephritis caused by renal stone disease was high (46% and 4.9% resp.), that of diabetic nephropathy (14.8%) not much different from EDTA figures, while adult polycystic kidney disease was seen in only four patients (1.2%, versus EDTA: 5.5%). Sixty-one percent needed antihypertensive medication to control the blood pressure, less than reported by the EDTA. Nineteen patients (5.8%) had pericarditis, 38% radiographic signs of renal bone disease and eight patients required parathyroidectomy. Only two patients had carpal tunnel syndrome. Over the 13-year period the number of HBsAg-positive patients was 14%, reflecting the high prevalence of this disease in the country, but in the last 4 5 years the incidence dropped markedly (3% in 1993). In 1993, 40% of the 67 patients on dialysis had hepatitis C (HCV) antibodies of which 19 (70%) were HCV RNA positive. Although tuberculosis (mainly extra-pulmonary) was common (9.2%), no patient died because of this disease. Cardiovascular factors contributed in the same degree to the causes of death as in Europe: 63% versus 62%. One hundred and fourteen patients (35%) had a successful kidney transplant. PMID- 7800204 TI - Phagocytosis by glomerular endothelial cells in infection-related glomerulopathy. AB - Glomerulonephritis in BALB/c mice following infection with Trypanosoma brucei is characterized by albuminuria and glomerular deposition of immunoglobulins. Electron-dense deposits are present in the mesangium, as well as subendothelially and subepithelially along the glomerular capillary wall. In this study the nature of intracytoplasmic, electron-dense, round structures observed in glomerular endothelial cells was investigated by immunoelectron-microscopy and enzyme histochemistry. The presence of these structures was related in time with the development of proteinuria. Mice from the C57BL10 strain, which upon infection develop glomerular immune complexes without proteinuria, were examined as well. The results demonstrated that the first endothelial changes, occurring 3-4 weeks after infection, were swelling of endothelial cells containing intracytoplasmic, electron-dense, round structures. These changes were seen prior to the onset of proteinuria, and were not present in glomeruli of mice that did not develop proteinuria. The endothelial granules were shown to contain immunoglobulins and typical lysosomal enzymes, providing evidence for phagocytosis by the glomerular endothelial cells. Liver endothelial cells did not show comparable changes. Thus, local phagocytosis by glomerular endothelial cells is shown to be a specific event in the development of glomerular disease. PMID- 7800205 TI - Heparin inhibits the binding of immune complexes to cultured rat mesangial cells. AB - Glomerular mesangial cells bear Fc receptors which bind immune complexes. Cross linking of these receptors induces the release of cytokines chemotactic for macrophages; the receptors may also be involved in the localization of large circulating immune complexes to the mesangium. Heparin has been shown to enhance the removal of antigen from the glomeruli of rats with chronic serum sickness glomerulonephritis, and from the isolated perfused rat kidney, so we investigated the effect of heparin on the binding of immune complexes by rat glomerular mesangial cells in culture. Heparin was found almost to eliminate binding of radiolabelled immune complexes to cultured rat mesangial cells. Pretreatment of the cells with heparin for 24 h followed by washing before the addition of immune complexes had the same effect. A parallel study showed that heparin had no effect on immune complex binding to thioglycollate-elicited rat peritoneal macrophages. To investigate the molecular properties required for this effect we treated cultured cells with high- or low-molecular-weight dextran sulphate. High molecular-weight dextran sulphate was found to inhibit the subsequent binding of immune complexes to the mesangial cells, although the effect appeared to be smaller than with heparin. Low-molecular-weight dextran sulphate had no detectable effect. Subsequent studies showed that heparin is also capable of removing immune complexes which have already bound to mesangial cells in vitro. We conclude that heparin can block the binding of immune complexes to the Fc receptor of cultured mesangial cells, but not to peritoneal macrophages. The success of heparin pretreatment indicates that the effect is on the cells rather than on the complexes in suspension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800206 TI - Influence of various calcium intakes on calcium-oxalate crystalluria in rats on sodium-oxalate diet. AB - Forty adult male Wistar rats were placed in metabolic cages on a Ca-deficient diet (0.1%) for 7 days and then on a Ca-deficient, Na-oxalate (NaOx) enriched diet (20 mg/100 g) for another 14 days. The animals were subdivided into three groups receiving three different types of mineral water: group I (n = 13), Badoit (Ca 222 mg/l); group II (n = 14), Contrexeville (Ca 467 mg/l); and group III (n = 13), Evian (Ca 78 mg/l). Another series of 25 rats (group I, n = 9; group II, n = 8; group III, n = 8) underwent the same study protocol, except that they received a normal Ca diet (1%). On the low-Ca diet, urinary Ca-Ox monohydrate (COM) crystals were observed only under the Na-Ox diet, with a mean crystal number significantly greater in group III (16.7 +/- 4.5 crystals/mm3) than in group I or II rats (2.5 +/- 1.5 or 4.1 +/- 1.5 crystals/mm3, respectively). Urinary Ca concentrations decreased in all groups (P < 0.001) under the Na-Ox diet, while urinary oxalate concentrations increased in all groups (P < 0.001). On the normal Ca diet, COM crystal excretion was observed only with the Na-Ox-enriched diet, but in this case feeding the Na-Ox diet did not modify urinary oxalate excretion. Ca/Ox ratio was significantly lower under 0.1% Ca diet than under normal Ca diet, related with the type and the number of crystals observed, demonstrating that assessment of crystalluria can provide an index of disease severity. Moreover, the hardness of the drinking water influences urinary COM crystal excretion only under a low-Ca, oxalate-rich diet, suggesting that the total calcium intake rather than the water calcium content is an important factor in the occurrence of Ca-Ox nephrolithiasis. PMID- 7800207 TI - Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus. AB - Progression of diabetic nephropathy from the stage of macroproteinuria with near normal renal function until start of dialysis was compared in 16 patients with type I and 16 patients with type II diabetes mellitus. The mean creatinine clearance at the beginning of the study was 89 +/- 13 ml/min/1.73 m2 in patients with type I and 81 +/- 6 ml/min/1.73 m2 in those with type II diabetes. Dialysis was started after a mean interval of 77 (44-133) months, when creatinine clearance had decreased to 8 +/- 2 ml/min/1.73 m2 in type I diabetic patients. The respective figures for type II diabetic patients were 81 (40-124) months and 7 +/- 2 ml/min/1.73 m2. The mean rate of decrease in creatinine clearance was 1.05 +/- 0.45 ml/min/month in type I and 0.91 +/- 0.41 ml/min/month in type II diabetes. The mean rate of decrease was 1.46 +/- 0.30 ml/min/month in type I diabetic patients with a systolic BP > 160 mmHg versus 0.80 +/- 0.42 ml/min/month with < 160 mmHg (P < 0.01). In the type II diabetics the respective figures were 1.38 +/- 0.40 ml/min/month versus 0.78 +/- 0.15 ml/min/month (P < 0.01). During the observation period the prevalence of coronary heart disease increased from 6 to 50% in type I and from 31 to 87% in type II diabetes. In conclusion, the rate of progression of diabetic nephropathy during the predialytic phase is similar in type I and type II diabetes; BP adversely affects the rate of progression to the same extent in both groups. PMID- 7800208 TI - Hyperhomocysteinaemia: a significant risk factor for cardiovascular disease in renal transplant recipients. AB - Moderate hyperhomocysteinaemia has been shown to constitute an independent risk factor for cardiovascular disease (CVD), a frequent cause of morbidity and mortality in renal transplant recipients (RTR). In these patients few data regarding both total homocysteine levels and their influence on cardiovascular risk have been reported. We therefore studied serum homocysteine levels in deep frozen sera from 42 kidney transplant recipients with a follow-up of 11 +/- 4.5 years (mean +/- SD) after transplantation. Eighteen patients had one or more ischaemic events (CVD (+)) and 24 patients had none (CVD (-)). Serum samples had been drawn 1-6 months prior to the first vascular event in CVD (+) patients and serum storage time was comparable in both CVD (-) and CVD (+) patients. Serum homocysteine levels were measured using a radioenzymatic method. Mean homocysteine level was significantly higher in 42 RTR males and females (15.5 +/- 6.3, 13.5 +/- 5.5 microM respectively) compared with 35 control subjects matched for age and sex (8.7 +/- 1.9, 7.5 +/- 1.9 microM, P < 0.001). The difference in serum homocysteine levels between CVD (+) and CVD (-) RTR nearly reached statistical significance in male patients (18.6 +/- 7.8 versus 13.1 +/- 3.4 microM, P < 0.06) but not in female patients (P = NS). In the CVD (+) group 11/18 patients had homocysteine levels > 14 microM (the upper limit in healthy controls) versus 7/24 in the CVD (-) group (P = 0.04). In these patients we simultaneously measured in the same serum samples, serum triglycerides, and total and HDL cholesterol, and calculated LDL cholesterol. By stepwise discriminant analysis and by logistic regression analysis in this relatively small patient population, only serum triglycerides and homocysteine were selected as risk factors associated with CVD. We conclude that significant hyperhomocysteinaemia is present in renal transplant recipients and represents a potential risk factor for cardiovascular disease in these patients. PMID- 7800209 TI - Modulation of platelet cytosolic calcium during erythropoietin therapy in uraemia. AB - Erythropoietin therapy for uraemic anaemia is associated with a high rate of hypertensive and thrombotic complications. The mechanism is unknown, but a change in cellular calcium control may be relevant to changes in blood pressure and thrombosis. Platelets were utilized as a model of vascular smooth muscle cells. The effects of erythropoietin therapy on platelet cellular calcium, assessed by fura-2, were measured in 25 patients receiving renal replacement therapy during a 6-month treatment period. Three patients failed to reach a target haemoglobin and were excluded from the analysis. Blood pressure increased in 11 of the remaining 22 subjects, eight requiring an increase in antihypertensive medication. There were no differences in cellular calcium control between the group in whom blood pressure rose and patients with stable blood pressure. Overall there was a fall of 24% in resting cytosolic calcium (baseline 69.2 +/- 5.1 to 52.5 +/- 3.0 nmol/l, P < 0.05) after 3 months of erythropoietin therapy. There was no change in the thrombin-stimulated peak response in the presence of extracellular calcium during therapy, although thrombin-stimulated intracellular release also fell at 3 months (baseline 769 +/- 61 versus 3 months 559 +/- 49 nmol/l, P < 0.01). This study suggests that intracellular free calcium control within platelets improves in response to erythropoietin therapy. However these changes appear not to be related to the development of hypertension. PMID- 7800210 TI - Low-dose aspirin does not prevent thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human erythropoietin. AB - Treatment of the anaemia of renal disease with recombinant human erythropoietin results in an improvement of haemostasis and an increased risk of thrombovascular accidents. In this prospective, placebo-controlled, double-blind, and cross-over study, the effects of low-dose acetylsalicylic acid (30 mg daily) on thrombotic and bleeding events during the initial period of treatment with erythropoietin in anaemic haemodialysis patients without previous thrombovascular accidents or known increased risk for thrombosis were investigated. During correction of the haematocrit and the first 3 months thereafter, group A (n = 68) received placebo and group B (n = 69) 30 mg acetylsalicylic acid daily. Cross-over took place after the 3rd month of a stable haematocrit. The study ended 3 months later. Target haematocrit (30-35%) was reached in 12.4 +/- 8 weeks (M +/- SD). In group A the bleeding time was 382 +/- 285 s, decreasing to 282 +/- 208 before cross over (P < 0.01), and increasing to 395 +/- 271 (P < 0.05) thereafter. In group B the bleeding time was 390 +/- 381 s, 406 +/- 267 (NS), and 285 +/- 238 (P < 0.05) respectively. Twenty-two thrombovascular accidents were seen (16%, 13 during acetylsalicylic acid and 9 during placebo, NS), including 17 fistula thromboses. The incidence of bleeding events was not significantly different between regimens. In conclusion, erythropoietin treatment resulted in a reduction of the bleeding time. When 30 mg acetylsalicylic acid was taken during the treatment, the bleeding time did not decrease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800211 TI - Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis. AB - Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy, and phosphate-binding agents are required in many chronic dialysis patients. Aluminium hydroxide and calcium carbonate are well-established phosphate binders, but their use is associated with toxicity or poor efficacy. Calcium acetate is known to be a potent phosphate binder, and has recently been used successfully in chronic dialysis patients. In this randomized cross-over trial in 31 chronic haemodialysis patients, equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each. Compliance was estimated from tablet counts, and biochemical parameters were measured at the end of each treatment period. Of the 31 patients 23 completed both treatment arms; of the remainder, three withdrew due to adverse symptoms, hypercalcaemia necessitated treatment withdrawal in two, and three died. Non-compliance was significantly higher with acetate (18.3% tablets not taken) than with carbonate (8.7%). Serum phosphate was significantly lower after treatment with acetate (1.51 mmol/l) than with carbonate (1.80), as was the Ca x PO4 product (3.59 vs 4.18 respectively) and PTH (17.8 vs 25.4 pmol/l respectively). Serum calcium was significantly higher after acetate therapy (2.40 vs 2.32 mmol/l). No significant difference was found for sodium, potassium, bicarbonate, urea, creatinine, and haemoglobin. This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate. For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated. Patient tolerability of calcium acetate was considerably poorer, probably due in part to tablet formulation and bulkiness, as well as possible direct gastrointestinal effects of the acetate salt. PMID- 7800213 TI - Treatment of dialysis-induced hypotension with L-threo-3,4-dihydroxyphenylserine. AB - L-threo-3,4-dihydroxyphenylserine (L-DOPS), a precursor of noradrenaline (norepinephrine), which is converted into noradrenaline when orally administered, was given orally to haemodialysed patients exhibiting dialysis-induced hypotension. In five patients given 300 mg L-DOPS plasma concentrations reached a peak of 1.43 +/- 0.59 micrograms/ml 6 h after administration and decreased slowly to disappear after 36 h. Plasma noradrenaline concentrations showed a significant increase (P < 0.05), reaching a peak of 1.28 +/- 0.64 ng/ml after 24 h and declined to 0.75 +/- 0.47 ng/ml by 48 h. Administration of L-DOPS to six patients during dialysis for 6 consecutive weeks showed no accumulation in the blood. Oral administration of 200-400 mg L-DOPS to 34 patients 1 h before dialysis prevented dialysis-induced hypotension and decreased the number of concurrent treatments required for hypotension. The signs and symptoms of hypotension were improved in 73.5% of the patients and persisted after dialysis in 64.7%. The preventive effect of L-DOPS was significantly more prominent in patients with predialysis systolic blood pressure less than 100 mmHg and in patients with non-diabetic nephropathy. L-DOPS appeared to be an effective and well-tolerated treatment for the prevention of dialysis-induced hypotension. PMID- 7800212 TI - Increased plasma levels of soluble tumor necrosis factor-receptors in uraemic patients: effects of dialysis, type of membrane, and anticoagulation method. AB - Enhanced levels of soluble TNF-receptors (sTNF-R) have been reported in patients with chronic renal failure. The aim of the present study was to evaluate the effects on sTNF-R levels in plasma of haemodialysis patients of the anticoagulation method and of the type of membrane used, as well as the variability of predialysis sTNF-R levels during time. All haemodialysis patients tested (n = 35) showed increased levels of both sTNF-R55 (72.4 +/- 5.7 ng/ml, P < 0.001) and sTNF-R75 (18.2 +/- 2 ng/ml, P < 0.001) before dialysis, as compared with normal healthy controls (< 2.5 ng/ml for both sTNF-R), confirming previous observations. sTNF-R levels were determined before and during haemodialysis at different time intervals in patients receiving either heparin (2500 U, 5000 U, or 10,000 U), low molecular weight heparin, or periodic saline flushing to prevent coagulation of the extracorporal circuit. A transient, small decrease in both sTNF-R levels occurred at the beginning of haemodialysis (t = 15 min) with all anticoagulation methods used. At the end of haemodialysis, sTNF-R55 and sTNF-R75 concentrations were only minimally affected (P > 0.05). Predialysis sTNF-R levels were similar in patients dialysed on either cellulose diacetate or polyacrylonitrile. Finally, there were only minimal variations in predialysis sTNF-R levels in individual patients during the 1 week observation period. Although the biological consequences of the increased TNF-binding ability of serum from haemodialysis patients is still unclear, it could play a role in the complex immunological perturbations of uraemic patients. PMID- 7800214 TI - Comparative mortality from cardiovascular disease in patients with chronic renal failure. AB - Patients with chronic renal failure show an excess mortality from cardiovascular disease (CVD). Over a 4-year period (1983-1986) we have prospectively studied 305 patients (177 men, 128 women) from a geographically constrained population entering a renal replacement therapy (RRT) programme. The development of new cardiovascular events and patient survival have been documented up to the end of 1990. We have determined the incidence of CVD amongst the patients compared to the general population of the region and assessed the predictive value for future cardiovascular events of risk factors present at the start of RRT. One hundred and fourteen patients experienced a new cardiovascular event. One hundred and fifteen patients died, 89 from CVD. Stratification by age and sex identified diabetes, previous coronary heart disease, and cardiomegaly to be significantly associated with an increased risk of a cardiovascular event, and diabetes, previous coronary heart disease, and accelerated hypertension to be significantly associated with an increased risk of cardiovascular death. Mortality from CVD was 10.1 times that of the corresponding general population, and was increased 44 times for patients with diabetes. Duration of RRT did not influence mortality rates. This excessive early mortality has significant implications for RRT programmes and further research is necessary to identify individuals at risk and the modifiable risk factors that could receive targeted interventional therapy. PMID- 7800215 TI - Prevention of acute cyclosporin nephrotoxicity by verapamil and atrial natriuretic factor in the rat. AB - Nephrotoxicity is the most common and important side-effect of cyclosporin (CsA) therapy. CsA alters renal haemodynamics with a reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistances (RVR). The present experimental study investigates whether verapamil or atrial natriuretic factor (ANF) are able to prevent the nephrotoxicity of CsA. All studies were conducted in an in-situ autoperfused rat kidney model which allows continuous measurement of renal blood flow without dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from 2.15 +/- 0.1 and 2.19 +/- 0.1 before CsA, to 1.29 +/- 0.16 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05), and GFR (from 0.14 +/- 0.1 and 0.13 +/- 0.01 before CsA, to 0.08 +/- 0.01 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05). CsA significantly increased RVR (from 9.5 +/- 0.73 and 9.8 +/- 0.78 before CsA, to 16.7 +/- 2.9 mmHg x min/ml 60 min after CsA administration) (P < 0.05). Verapamil pretreatment (as continuous intrarenal infusion at the rate of 1.25 micrograms/kg/min) attenuated the fall in GFR (from 0.16 +/- 0.01 and 0.19 +/- 0.03 ml/min/100 g before CsA to 0.20 +/- 0.05 ml/min/100 g BW, 60 min after CsA administration) (NS) and in RBF (from 2.42 +/- 0.2 and 2.6 +/- 0.22 ml/min/100 g before CsA to 1.79 +/- 0.17 ml/min/100 g BW, 60 min after CsA administration (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800217 TI - 99mTc-DMSA imaging with tomography in renal transplant recipients with abnormal lower urinary tracts. AB - This study examined whether renal parenchymal imaging using 99mTc DMSA scintigraphy with tomography is a sensitive measure of renal scarring in renal transplant recipients with an abnormal lower urinary tract and whether such scars correlate with impairment of renal function. Three groups of patients were compared: group 1, patients with an abnormal lower urinary tract and deteriorating renal function (n = 9); group 2, abnormal lower urinary tract and stable renal function (n = 5); and group 3, normal lower urinary tract and deteriorating renal function (n = 8). Eight of the nine patients in group 1 had multiple scars visible on 99mTc DMSA scans and this correlated with histology when a renal biopsy was performed; the only patient without scars had a transplant glomerulopathy. The presence of scars was associated with either raised intravesical pressures or recurrent urinary tract infections (UTIs). Only one patient in each of groups 2 and 3 had visible scars and both these patients had a history of recurrent UTIs. Patients in group 3 with deteriorating renal function due to chronic rejection documented by biopsy did not have cortical scars visible with 99mTc DMSA tomography. 99mTc DMSA scanning with tomography is a useful investigation in the management of renal transplant patients with declining renal function; multiple scars may indicate abnormal lower urinary tract function and are not seen in chronic rejection. PMID- 7800216 TI - Acute haemodynamic and renal effects of cyclosporin and indomethacin in man. AB - A single oral dose of cyclosporin (12 mg/kg) was given to healthy volunteers (n = 9) on day 2 with or without indomethacin pretreatment (100 mg day 1 + 100 mg day 2). All parameters reported were analysed after a water-loading protocol on day 2. As a peak drug effect within 4 h of drug ingestion on day 2 cyclosporin on its own increased mean arterial pressure by 13% (P < 0.05) without causing any sodium retention or renal vasoconstriction. Indomethacin pretreatment did not accentuate this hypertensive effect of cyclosporin. The earliest renal effect observed with cyclosporin on day 2 was on water handling with a marked antidiuretic effect. Free-water clearance decreased by a maximum of 48% (P < 0.05) following cyclosporin. Indomethacin pretreatment induced a similar antidiuresis on day 2 but cyclosporin did not augment this antidiuresis any further. This suggests that inhibition of vasodilator prostaglandins within the kidneys may mediate the antidiuretic effect of cyclosporin such that in the presence of indomethacin, cyclosporin had no additional effect. The inhibition of intrarenal prostaglandins by a single dose of indomethacin did not, however, produce any acute cyclosporin induced change in glomerular filtration rate or renal blood flow. PMID- 7800218 TI - Characterization of the anti-A antibody binding in an ABO-incompatible living donor renal transplantation. AB - A 57-year-old female, blood group B, with polycystic kidney disease, received an ABO-identical, HLA-A,B,DR 5-mismatched renal allograft in 1986. Due to graft artery thrombosis and vascular rejection, she lost the kidney 6 months after transplantation and developed HLA antibodies with a panel reactivity of 99%. Despite 5 years on a European waiting list for highly immunized patients, she was not offered a second kidney. An attempt to remove her HLA antibodies by plasmapheresis combined with cyclophosphamide therapy did not succeed. Her 53 year-old HLA-identical, but ABO-incompatible sister (blood group A1), was then accepted as a donor. After immunoadsorption on Biosynsorb-A columns, transplantation was performed. The post-transplant course was uneventful without any signs of rejection. Studies on the anti-A antibody binding characteristics before and after immunoadsorption and after transplantation, showed that IgM and IgG antibodies recognizing the A trisaccharide epitope based on the type 1, 2, and 4 core saccharide chains, were effectively removed by Biosynsorb-A adsorption, but the column failed to remove anti-A antibodies recognizing the A type 3 antigen. These antibodies probably requires part of the core saccharide chain for binding. The presence of these antibodies did not seem to influence the outcome of the ABO-incompatible transplantation. PMID- 7800220 TI - Acute hypernatraemia during bicarbonate-buffered haemodialysis. AB - Five patients on maintenance haemodialysis were exposed to varying degrees of hypernatric dialysate, leading to acute hypernatraemia (plasma sodium concentrations 158 mmol/l to 179 mmol/l). With the exception of one patient, who developed pulmonary oedema, symptoms were minimal and in each case hypernatraemia was corrected without residual complications. The hypernatric dialysate resulted from a granular and less soluble batch of sodium bicarbonate powder. The extra effort required to dissolve the powder caused CO2 to be shaken out of solution, producing sodium carbonate and raising the pH. Mixing calcium from the 'acid' concentrate with excess carbonate in the 'bicarbonate' concentrate led to rapid precipitation of calcium carbonate on the conductivity monitoring cells. Dialysate conductivity was incorrectly sensed as low by the coated conductivity cells, so that an increasing amount of 'acid' concentrate, with its accompanying electrolytes, was delivered to the patient. When the granular powder was ground to a fine powder, passed through a 125 microns sieve and gently dissolved, the machine operated normally. We recommend that sodium bicarbonate powder is supplied with a sieve size no greater than 125 microns, kept dry to prevent the formation of large crystals, and dissolved gently. PMID- 7800219 TI - Increased renal allograft thrombosis in CAPD patients. AB - In a retrospective analysis of 202 renal transplant procedures in the years 1989 1992 we identified an excess of grafts lost from primary renovascular thrombosis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared = 9.63; P < 0.01). All graft losses from thrombosis occurred within 16 days of surgery. Possible predisposing causes were identified in three patients. Donor age was greater in CAPD patients losing their kidneys from thrombosis compared to the overall CAPD group [mean (SD) years, 43.0(12.9) versus 29.1(15.8); P = 0.01] whereas no significant difference in haematocrit, platelet count, antibody status, cyclosporin use, peroperative hypotension, primary diagnosis, smoking, or diabetes mellitus was found. Data from the EDTA registry for 1990-91 show that graft loss from primary renovascular thrombosis in UK-treated patients was reported in 7.1% of CAPD recipients compared with 1.8% in haemodialysis. We suggest that CAPD patients are at greater risk of graft loss from renovascular thrombosis than HD patients and may require more intensive fluid and anticoagulant treatment in the perioperative period. PMID- 7800221 TI - Bradycardia as a presenting feature of late postpartum eclampsia. PMID- 7800222 TI - Hypokalaemic paralysis as the presenting manifestation of primary Sjogren's syndrome. PMID- 7800223 TI - Renal involvement in type I glycogen storage disease. Report of one case. PMID- 7800224 TI - Acute interstitial nephritis with severe but reversible renal failure due to streptokinase. PMID- 7800225 TI - Endocarditis due to corynebacteriaceae in a kidney transplant patient. PMID- 7800226 TI - Renal allograft dysfunction due to vesicoureteric obstruction by nodular malakoplakia. PMID- 7800227 TI - Haemolytic uraemic syndrome in a renal transplant recipient during OKT3 therapy. PMID- 7800228 TI - Mucormycosis in transplant recipients: possible case-case transmission and potentiation by cytomegalovirus. PMID- 7800230 TI - Calciphylaxis in renal failure. PMID- 7800229 TI - Complete regression of recurrent diffuse malignant lymphoma after withdrawal of cyclosporin A in a renal transplant recipient. PMID- 7800231 TI - Improving the number of organ donors. PMID- 7800232 TI - Successful treatment of massive uraemic tumoral calcinosis with daily haemodialysis and very low calcium dialysate. PMID- 7800233 TI - Nocardial psoas and perinephric abscess in a renal transplant treated by surgery and antibiotics. PMID- 7800235 TI - Erythropoietin dose requirement in a patient with beta-thalassaemia and chronic renal failure. PMID- 7800234 TI - Cytomegalovirus infection in a renal transplant patient masked by hepatitis C. PMID- 7800236 TI - Treatment with expandable endovascular prosthesis (Palmaz) to resolve an aneurysmal zone in an arteriovenous fistula (AVF) in a haemodialysis patient. PMID- 7800237 TI - Efficacy of intradermal injection of recombinant hepatitis B vaccine in dialysis patients. PMID- 7800238 TI - International symposium on acute renal failure. 20-23 June 1993, Halkidi, Greece. Proceedings. PMID- 7800239 TI - Acute renal failure: the dawn of dialysis and the roaring 50s. PMID- 7800240 TI - Acute renal failure and multiorgan failure. AB - Acute renal failure is often seen in the context of multiorgan failure, and thus there is likely to be a common mechanism based on septicaemia or endotoxaemia. The role of gut mucosal dysfunction during shock or in infected ICU patients is a potential common factor. With that in mind the probable role of endotoxin as a causative agent in acute renal failure is addressed. PMID- 7800241 TI - Acute renal failure and myeloma. PMID- 7800242 TI - Virus-related acute renal failure. The clinical course and outcome of haemorrhagic fever with renal syndrome. PMID- 7800243 TI - Inhaled mycotoxins lead to acute renal failure. AB - Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat. PMID- 7800244 TI - Acute renal failure in patients with severe civilian trauma. AB - We reviewed our experience with patients suffering from civilian trauma to identify risk factors for the development of acute renal failure (ARF) and ARF outcome. Of the 437 patients consecutively admitted to a surgical intensive care unit (SICU), 206 had a SICU stay of at least 1 day and ARF developed in 30 of these patients. All ARF patients had additional organ system failure (OSF). Pre existing chronic disease (including chronic renal failure), malnutrition, injury severity score (ISS), number of organs injured, sepsis, and all OSFs before the onset of ARF were factors predisposing to ARF. Mortality was 40%. Chronic disease, malnutrition, ISS, failure of cardiovascular, pulmonary, hepatic, and neurological systems (either before and after ARF) were significantly associated with mortality. When OSFs were considered in their temporal relationships to ARF, only cardiovascular and pulmonary failure before, and gastrointestinal failure after, the onset of ARF were related to mortality. An increasing number of OSFs increased mortality, both before and after the development of ARF. However, the number of OSFs before was significantly greater than after ARF. Sepsis was not associated with increased mortality. Thus, the outcome of ARF patients with critical trauma seems to be dependent on factors predisposing to ARF. Our results suggest that more attention must be paid to prevention of these precipitating conditions. PMID- 7800246 TI - Antibiotic-related nephrotoxicity. AB - The toxicity of aminoglycosides is related to their concentrative uptake by proximal tubular cells and their capacity to interact with critical intracellular targets. Concentrative uptake is mediated by adsorptive endocytosis across the apical membrane followed by sequestration within lysosomes. The fundamental mechanism underlying the toxicity of these organic polycations is their capacity to interact electrostatically with and disrupt the metabolism of anionic phospholipids, especially the phosphoinositides. Polyaspartic acid, a polyanionic peptide, protects against aminoglycoside nephrotoxicity by forming electrostatic complexes with these drugs and inhibiting their interaction with critical intracellular targets. The selective toxicity of beta-lactams towards renal proximal tubular cells is related to their concentrative uptake via the organic anion transport system. Lipid peroxidation appears to play a major role in the toxicity of cephaloridine. Depressed mitochondrial respiration secondary to acylation of the mitochondrial transporter for succinate has been implicated in the pathogenesis of toxicity caused by other cephalosporins and carbapenems. The predilection of the kidney for amphotericin B toxicity is unclear as little drug is excreted by the kidneys. Toxicity is manifested by increased renal vascular resistance, depression of RBF and GFR, and altered tubular function that reflects the capacity of this drug to interact with cholesterol-containing membranes and increase membrane permeability to ions including potassium, hydrogen, calcium, and magnesium. PMID- 7800245 TI - Metformin-associated lactic acidosis in diabetic patients with acute renal failure. A critical analysis of its pathogenesis and prognosis. AB - To determine the respective role of metformin accumulation and tissue hypoxia in triggering metformin-associated lactic acidosis (MALA), we measured plasma (PM) and red blood cell (RM) metformin concentrations in 14 patients with MALA and in 58 diabetic patients on well-tolerated chronic metformin treatment. In this control group RM was 0.9 +/- 0.5 mg/l. In MALA, lactic acidosis was of comparable severity whether there was significant cellular metformin accumulation (9 patients with severe renal failure) or not (5 patients with less severe renal failure). Factors of hypoxia were found in all patients except three with isolated anuria and major metformin accumulation. Early mortality was low in patients with metformin accumulation (no rapid death with the exception of two patients with end-stage hepatic failure) whereas it was high in those with metformin accumulation (4 patients died rapidly). In conclusion, MALA is not always associated with metformin accumulation. The prognosis of MALA depends mainly not upon the degree of metformin accumulation but rather upon the severity of hypoxic factors. PMID- 7800247 TI - Mechanism of gentamicin nephrotoxicity in rats and the protective effect of zinc induced metallothionein synthesis. AB - We examined the role of reactive oxygen metabolites and the protective effect of zinc-induced metallothionein (MT) synthesis on gentamicin nephrotoxicity both in vivo and in vitro. In vivo study we found that the MT content of renal cortex of the zinc preinjected rats was significantly increased, and proximal tubular necrosis and acute renal failure caused by injection of gentamicin were ameliorated. In suspended proximal tubules (PT), Na(+)-K(+)-ATPase activity and DNA synthesis were suppressed by the addition of gentamicin, but in zinc pretreated rats' PT, these were not suppressed by the addition of gentamicin. Meanwhile MDA and hydroxyl radicals were significantly less in zinc-pretreated rats' PT compared to that in the control. Finally, we found that gentamicin enhanced superoxide anion and hydroxyl radical productin in renal cortical mitochondria. Superoxide anion could be suppressed by SOD and hydroxyl radical could be scavenged by DMSO, DFO and CAT. Our data confirm that hydroxyl radicals play a role in the pathogenesis of gentamicin nephrotoxicity, gentamicin can induce suppression of Na(+)-K(+)-ATPase activity and DNA synthesis in rats' proximal tubules leading to renal injury; this injury may be relevant to reactive oxygen metabolites generated by gentamicin. Renal cortical mitochondria is the source of reactive oxygen metabolites, which induces renal injury, and zinc induced metallothionein synthesis could ameliorate gentamicin nephrotoxicity via scavenging reactive oxygen metabolites. PMID- 7800248 TI - Radiocontrast-induced nephropathy. AB - Significant renal insufficiency defined as a stable SCr > 1.5 mg/dl is the single most important risk factor for RCIN. Based on the outcome data summarized, the occurrence of RCIN should be avoided, since significant deterioration of renal function occurs in one of every four patients. Clearly volume depletion should be corrected before administering RCM. In high-risk patients a hydration protocol should be initiated before the procedure and continued for at least 2 h after the procedure. At least one large cooperative study has reported a significant reduction in RCIN when LORCM are compared to HORCM. Limiting the total volume of RCM used for an individual study also reduces the incidence of RCIN. While indications for invasive studies with RCM continue to expand, especially for elderly and other high-risk groups, using the above recommendations as guidelines should minimize the risk of RCIN while still providing the critical information needed to develop a clinical management plan. PMID- 7800249 TI - Mechanisms of cell injury in ATP-depleted proximal tubules. Role of glycine, calcium, and polyphosphoinositides. AB - Increase of intracellular free Ca2+ (Caf) plays an important role in the deterioration of cell structure that occurs during depletion of adenosine triphosphate (ATP). On the other hand a form of Ca2+ independent cell injury due to glycine deficiency has also been recognized. Normally high intracellular gradients of glycine are dissipated during ATP depletion. Under these circumstances exogenous glycine protects cells and preserves structure independently of metabolism. We have examined the specific contributions of calcium and glycine to the injury process in isolated rabbit proximal tubules depleted of ATP by exposure to a metabolic inhibitor, or additionally made permeable to calcium ions by an ionophore. Tubules were incubated in high or low Ca2+ media (1.25 mM or 100 nM Ca2+) to attain high concentrations of Caf or 'clamp' Caf in the physiological range. Our results showed that structural breakdown in proximal tubule cells is compartmentalized. Increase of Caf leads to specific patterns of membrane damage and phospholipid hydrolysis. On the other hand glycine deficiency leads to a unique membrane defect that occurs independently of phospholipid breakdown and is fully expressed even if calcium mediated injury is prevented by low Ca2+ conditions. Furthermore, the specificity of glycine was emphasized by its ability to maintain membrane continuity and thus dramatically delay lethal injury in spite of severe structural damage caused by massive increases of Caf. PMID- 7800250 TI - International standardization in renal allograft biopsy reporting: a model for a new approach to renal pathology. AB - As we prepare to enter a new century it is reasonable to ask whether our current classification system of renal pathology and descriptive approach to renal biopsy interpretation will be appropriate to the medicine of the future. Assessment of that special category of acute renal failure represented by early post-transplant biopsies is becoming much more quantitative, therapy-oriented, and pathogenesis based. It would be highly beneficial to the field if similar changes occurred in our approach to native kidney biopsies. We need to provide tighter linkage between exciting new developments in the research laboratory and the clinical practice of renal pathology. In a field largely limited to traditional empirical therapies, we need to be developing new pathogenesis-oriented therapeutic approaches to native kidney disease based on the results of enlightened renal pathology research. PMID- 7800251 TI - Sepsis-associated acute renal failure: some potential pathogenetic and therapeutic insights. PMID- 7800252 TI - Loop diuretics and renal vasodilators in acute renal failure. AB - Loop diuretics are powerful drugs able to increase urinary sodium and water excretion even in conditions of marked impairment of renal function. Loop diuretics are useful in preventing or ameliorating the course of acute renal failure. This effect may be obtained when they are used within 18 h after the ischaemic and/or toxic event. Loop diuretics reduce tubular work, providing resistance to cellular ischaemia. Other important beneficial effects include tubular wash-out of cellular debris and inhibition of tubuloglomerular feedback. Among vasodilators, dopamine, when used at 'dopaminergic dosage' is useful in preventing acute renal failure. Its efficacy is demonstrated in several situations of renal hypoperfusion, i.e. salt depletion, cyclosporin administration, and therapy with recombinant interleukin 2 in cancer patients. According to our studies it appears that dopamine should be used in the early phases of acute renal failure to improve renal perfusion, re-establish glomerular filtration rate, and increase tubular flow. PMID- 7800253 TI - Factors related to multiple organ system failure and mortality in a surgical intensive care unit. AB - We retrospectively studied the relative contribution of factors related to the extent of multiple organ system failure (MOSF) and mortality, using multivariate methods to account for the interactions between studied factors, in 538 consecutive patients admitted to a surgical intensive care unit during a 1-year period. MOSF (MOSF score > or = 5) occurred in 88 (16%) of patients. Multiple linear regression selected advancing age, malnutrition, APACHE II score, shock and coma on admission, number of blood transfusions, use of H2 receptor antagonists or antacids, bacteraemia and intra-abdominal infection as independent factors related to the MOSF score. MOSF mortality was 52% and was a major cause of death in critically ill surgical patients. Multiple logistic regression selected advancing age, malnutrition, bacteraemia, APACHE II and MOSF score as major predictors of mortality. Advancing age, malnutrition, shock and coma on admission, transfusion requirement and use of H2 receptor antagonists or antacids may impair host defences of the gastrointestinal tract and enhance the vulnerability for invasive infection, thereby aggravating the severity of existing MOSF. Together with the predominance of Enterobacteriaceae in infected patients, these results suggest that translocation of intestinal bacteria and endotoxin may be important in the evolution and perpetuating the MOSF syndrome. Our results may be useful in devising strategies to prevent or limit the evolution of MOSF and to improve survival in patients with critical illness. PMID- 7800254 TI - Risk factors influencing survival in ICU acute renal failure. AB - Factors influencing survival in ICU patients with acute renal failure (ARF) requiring dialysis were analysed from data collected prospectively in an ARF registry. A total of 363 patients were analysed. Overall mortality was 79.1% and did not differ between medical and surgical patients. Factors associated with an increased risk of dying included the development of any concomitant organ system failure, the number of failed organs, APACHE II score at the time of renal consultation for medical patients, pre-existing chronic liver disease, and the number of days from ICU admission to institution of dialysis. Male gender reached borderline significance. Survivors recovered renal function and discontinued dialysis in 65.7% of cases. We conclude that mortality rates for ARF in ICU patients continues to be high. Multi-system organ failure (MSOF) occurs frequently and is the major cause of death. PMID- 7800255 TI - Basic therapeutic requirements in the treatment of sepsis in acute renal failure. AB - Acute renal failure (ARF) is a common manifestation of a septic condition which very often complicates surgical and traumatic events. The release of endotoxin, a lipopolysaccharide (LPS) from the cell wall of Gram-negative bacteria, and subsequently of numerous host mediators, is the initiating event of sepsis syndrome and eventually of septic shock. Particularly interesting is the observation that not only endotoxins but also Staphylococcus aureus which does not produce endotoxins induce the same cardiovascular changes of septic shock. The main aspect of septic shock is the inadequate oxygen supply to the body tissues. However, despite the documented myocardial depression in the course of septic shock, myocardial ischaemia is not to be considered a contributing factor, and the coronary blood flow is normal or even increased. Protein hypercatabolism can be at best only limited; in any case the optimal protein-sparing effect was observed with 1.5 g/kg proteins. Recently monoclonal antibodies to endotoxin core glycolipid have been developed; they are: (a) E5, a murine IgM anti-lipid A monoclonal antibody; (b) HA-1A, a human monoclonal antibody to endotoxin core glycolipid. In conclusion, hypercatabolic septic patients should be managed in an intensive care environment where a continuous monitoring of fluids, electrolytes, and acid-base disorders can be achieved. Surgical search of septic foci, and wide spectrum antibiotic therapy are fundamental measures to combat cytokine and vasodilator production which impair tissue perfusion and create the premise of a shock status complicated by lactic acidosis. Dialysis treatment is a further complementary but fundamental approach that allows a large fluid and nutritional intake and a continuous correction of electrolyte and acid-base disorders. PMID- 7800256 TI - Continuous therapy for complicated acute renal failure. PMID- 7800257 TI - Continuous renal replacement therapies in the treatment of acute renal failure in intensive care patients. Part 1. Theoretical aspects and techniques. PMID- 7800258 TI - Continuous renal replacement therapies in the treatment of acute renal failure in intensive care patients. Part 2. Clinical indications and prescription. PMID- 7800259 TI - Plasmapheresis as a therapy in specific forms of acute renal failure. PMID- 7800260 TI - Nutritional considerations in the treatment of acute renal failure in septic patients. PMID- 7800261 TI - Cell shape changes and detachment in cell culture: models of renal injury. AB - Loss of tubular cell adhesion may be important in the pathophysiology of injury to renal tubular cell epithelium. In-vitro model systems have been utilized to examine altered cell adhesion in response to hypoxic/anoxic and oxidant-induced cell injury. Alterations in cell cytoskeleton and cell surface adhesion molecules, including L-CAM and integrins, have been demonstrated in these systems, and are probably important in the pathogenesis of altered structure and function in response to injury in renal tubular epithelium. PMID- 7800262 TI - Long-term follow-up of acute renal failure. PMID- 7800263 TI - Severity of acute renal failure: the need of measurement. PMID- 7800264 TI - Potential role of integrins in acute renal failure. AB - Many cell adhesion molecules probably contribute to the pathogenesis of acute renal failure. This review focuses on the potential importance of integrins. Integrins are a family of molecules that mediate cell-matrix and cell-cell adhesion, and are found on almost all cells. After acute renal injury, tubule epithelial cell-cell contacts (mediated by many molecules including uvomorulin and possibly integrins) are disrupted, as is the cytoskeleton. Detachment of viable tubule epithelial cells from the basement membrane has also been documented following acute renal injury. Such detachment would lead to back-leak of glomerular filtrate and could also be important in the production of cellular casts. As the attachment of the cytoskeleton to integrin is critical to cell matrix adhesion, it is likely that cytoskeletal disruption is one of the mechanisms contributing to cell detachment. Integrins are also likely to be important in repair, as integrins will probably participate in migration along the basement membrane and may also influence cell function during the redifferentiation process. Finally, leukocyte integrins will probably play a role in the migration of leukocytes into areas of injury and also be critically important to their function. PMID- 7800265 TI - Cellular defence mechanisms against ischaemic and toxic injury. PMID- 7800266 TI - Morphometric studies of acute renal failure using anti-brush-border and other antisera. AB - Correlations have been shown between renal excretory function and the extent of immunohistological staining in the kidney of proximal tubular brush border and Tamm-Horsfall protein. These findings confirm the importance of the integrity of the proximal tubule in control of the glomerular filtration rate and also show that the thick limb of the loop of Henle is damaged, as well as the proximal tubule, in renal failure. PMID- 7800267 TI - Role of infection in the genesis of acute renal failure. AB - While most experimental models of acute renal failure (ARF) involve ischaemic or toxic damage to the kidney in non-infected animals, a surprisingly large proportion of patients with ARF exhibit signs of septicaemia or systemic reaction to local infections. This clinical observation suggests an important role of infection-related mediator mechanisms in the genesis of ARF. Another important aspect is the occurrence of ARF in the context of infections with nephrotropic viruses (e.g. hantavirus accounting for approximately 5% of non-surgical ARF in Germany) and nephrotropic bacteria (e.g. leptospirosis). PMID- 7800268 TI - Bacterial factors in septic shock. PMID- 7800269 TI - Pathogenesis of acute renal failure during sepsis. AB - Acute renal failure (ARF) is often a component of multiple organ system failure in critically ill patients. Sepsis (i.e. systemic bacterial infection) is a major factor in the aetiology of ARF and this is primarily caused by sepsis-induced cardiovascular and pulmonary failure. This association suggests that systemic haemodynamic factors, leading to severe and persistent renal hypoperfusion, play a key role in the development of ARF. However, ARF in the course of sepsis or endotoxaemia may not be solely due systemic or renal haemodynamic changes, since humoral and cellular reactions may also have an adverse effect on renal function. This review will address the haemodynamic and non-haemodynamic factors and their interaction in the development of ARF during sepsis. PMID- 7800270 TI - Role of arachidonic acid metabolites in acute renal failure and sepsis. PMID- 7800271 TI - Renal epidermal growth factor and insulin-like growth factor I in acute renal failure. PMID- 7800272 TI - PAF-cytokine autocatalytic feed-back network in septic shock: involvement in acute renal failure. PMID- 7800273 TI - Role of endothelin and tumour necrosis factor in the renal response to sepsis. AB - A rapidly increasing body of evidence is implicating endothelin and TNF in the pathogenesis of septic acute renal failure. TNF causes renal damage by recruiting leukocytes, accelerating fibrin accumulation, promoting cell lysis, stimulating the release of vasoconstrictor substances, and other mechanisms. ET-1 causes renal dysfunction in sepsis and endotoxaemia primarily by evoking severe reductions in RBF and GFR. While these are only two of the many agents that mediate renal dysfunction during sepsis, they stand out by virtue of their combined ability to modulate numerous inflammatory pathways and to elicit marked alterations in renal function. Clearly the development of specific TNF and endothelin antagonists holds out promise for the treatment and prevention of septic acute renal failure. PMID- 7800274 TI - New aspects in pathogenesis of acute renal failure. PMID- 7800275 TI - Clinical studies on cytokines in sepsis: role of serum cytokines in the development of multiple-systems organ failure. AB - The universal finding of a persistently elevated serum TNF level after 12 h in patients who go on to develop MSOF and die suggests that factors other than peak intensity of intravascular proinflammatory response determine survival. The persistence of elevated levels of TNF in the serum of patients who progress to MSOF suggests an aetiological relationship between continual activation of the immune response and remote organ dysfunction in critically ill patients. PMID- 7800276 TI - Sepsis and SIRS. PMID- 7800277 TI - Commissioner Fishman takes oath of office. PMID- 7800279 TI - Environmental lung disease in New Jersey. AB - The lungs are peculiarly susceptible to insults that are experienced indoors and outdoors, infectious and noninfectious. Diagnosis is made through history and awareness of the increasing prevalence and number of causes of environmental lung disease. PMID- 7800280 TI - Current concepts in chronobiology and medicine. AB - Circadian rhythms must be considered as potential causes of medical problems if they are disrupted. These problems can be treated, with drugs, light, and chronotherapeutic techniques. Utilizing chronobiologic principles, some patients may be able to cope and overcome desynchronization. PMID- 7800278 TI - Human health effects associated with hazardous waste sites. AB - Many hazardous waste sites contain chemicals that cause serious disease in humans. However, adverse effects are uncommon. Evidence for harm comes principally from epidemiologic studies in which proof of exposure usually is lacking. PMID- 7800281 TI - Safe concentrations for dermal allergens in the environment. AB - Recent work studies have examined the relationship between allergen dose per unit of skin surface exposed and the elicitation of response for chromium. The use of such data to arrive at levels in environmental contactants is discussed with reference to soil contaminated with chromium. PMID- 7800282 TI - The environment and cancer in New Jersey. AB - Tumorigenesis involves a complex series of steps. These steps are influenced by genetic predisposition and by lifestyle, tobacco and alcohol use, diet, and occupation. The way a person chooses to or is forced to live will influence the risk of developing cancer. PMID- 7800283 TI - Cardiopulmonary effects of environmental tobacco smoke. AB - Passive smoking causes pulmonary and cardiovascular disease in children and adults. Environmental exposure to tobacco smoke in the home and in the workplace puts nonsmokers at risk and creates significant health and economic consequences. PMID- 7800284 TI - Sharing the toxic burden in New Jersey. AB - As toxic pollution spreads throughout New Jersey, the environment induces illness and the fear of illness in an ever-increasing population. The questions to ask physicians and residents of New Jersey are: Who will share the burden? What is the cost of this burden? PMID- 7800285 TI - Medical and environmental surveillance. AB - Comparisons and contrasts are made between medical and environmental surveillance in New Jersey. These two approaches can be used together to address questions of association and prevention in occupational and environmental medicine, a field that needs to be expanded. PMID- 7800287 TI - Long-term care for Californians. PMID- 7800288 TI - Law for the nurse manager: physician malpractice. PMID- 7800286 TI - Assessing human health effects from chemical contaminants in drinking water. AB - Epidemiologic studies in New Jersey have examined the relationship between exposure to water contaminants and the occurrence of leukemias, non-Hodgkin's lymphomas, and adverse reproductive outcomes. Public drinking water supplies need to be monitored on a continual basis. PMID- 7800289 TI - Marketing subacute care services. PMID- 7800290 TI - Ethics for, in, and about nursing administration. PMID- 7800291 TI - Legislative effects: what's next? A voice in the wilderness: what can I do? PMID- 7800292 TI - Technology: nursing the system. Taking the future on the CHIN. PMID- 7800293 TI - A follow-up evaluation to a needle-free i.v. system. AB - In 1989, one hospital noted a high rate of puncture wounds among healthcare workers, many injuries considered preventable. Beginning in 1990, strategies were developed in conjunction with the hospital's Blood and Body Fluid Exposure Task Force. In 1991, the hospital instituted a needle-free system in addition to employee and product educational programs. The study's results show a significant decrease in the number of injuries. PMID- 7800294 TI - Improving technology: blood glucose testing. AB - Nurses frequently monitor blood glucose at the patient's bedside, allowing timely assessment and interventions. To meet the Joint Commission on Accreditation of Health Organization's requirements and guidelines from National Committee on Clinical Laboratory Standards and College of American Pathologists, quality control compliance must be maintained. After testing three blood glucose monitors, one institution selected a machine that eliminated handwritten documentation, ensured quality control testing, and improved ease of use. PMID- 7800295 TI - Upgrading systems: a new pager. AB - A paging system was adopted to interface with an existing nurse call system to improve access and communication. A comprehensive, written message instantly reports the problem, location, urgency, and action to take. Contacting a nurse quickly and clearly is of paramount concern when delivering quality patient care. PMID- 7800296 TI - Health-oriented telecommunication: a community resource. AB - Telecommunication networks that link medical information with the community can support home caregivers while providing skills training and crisis intervention to prevent unnecessary hospitalization. Health-oriented telecommunications direct the traditional focus from intervention to prevention. Consumers become empowered with knowledge allowing them to participate in their healthcare and lifestyle decisions. PMID- 7800297 TI - A mentoring relationship: two viewpoints. AB - A mentoring relationship can be a dynamic process for both participants, one filled with increased self-awareness, commitment, and mutual respect. The time spent with a mentor guides the transition of theory into practice while clearly expressing the humanistic and caring qualities of the nurse administrator. PMID- 7800298 TI - The Midwest flood of 1993: surviving prolonged water loss. AB - The Midwest Flood of 1993 was one of the most devastating and challenging disasters in Iowa's history. The city's water supply became contaminated, leaving more than 250,000 residents and all seven metropolitan medical centers without water. Despite heroic sandbagging efforts, floodwaters invaded the Des Moines water treatment plant's filtration system. The major strategies used at this facility during the disaster provide a framework for effective, coordinated emergency response. PMID- 7800299 TI - Managing waste: reduce its generation. PMID- 7800300 TI - Facilitating surgical patients through home health intervention. PMID- 7800301 TI - Surviving implementation of a patient care information system. PMID- 7800302 TI - The ghost of Jacob Marley... PMID- 7800303 TI - The transitional years and beyond. PMID- 7800304 TI - Sonographic measurement of nuchal skinfold thickness for detection of Down syndrome in the second-trimester fetus: a multicenter prospective study. The AFDPHE Study Group. Association Francaise pour le Depistage et la Prevention des Handicaps de l'Enfant. AB - OBJECTIVE: To determine the sensitivity and specificity of soft-tissue nuchal fold measurement in the second-trimester fetus for the detection of trisomy 21. METHOD: Thirty-six investigators in 12 centers measured nuchal skinfold thickness in 3308 fetuses of 14-24 weeks' gestation. All mothers were referred for amniocentesis because of age, history of genetic disorder, or laboratory findings. Those referred with an ultrasound indication for amniocentesis, including nuchal-fold thickening, were excluded. RESULTS: Overall, nuchal skinfold was 6 mm or more in 8.5% of chromosomally normal fetuses and in 38% of those with trisomy 21. A false-positive rate below 5% was obtained by 81% of the investigators. Raising the cutoff of normality to 7 mm after 18 weeks' gestation improved specificity. CONCLUSION: Although the diagnostic value of this sign in skilled hands could allow its use as an indication for genetic amniocentesis at the second trimester, the method does not appear suitable for population screening because of the high variability in the results among the investigators. PMID- 7800305 TI - Clinical and biologic prognostic factors in breast cancer diagnosed during postmenopausal hormone replacement therapy. AB - OBJECTIVE: To ascertain the influence of hormone replacement therapy on clinical and biologic prognostic factors of breast cancer. METHODS: Between 1976-1992, we treated 1081 postmenopausal women for breast cancer at our institution. Of these, 68 were undergoing postmenopausal hormone replacement therapy at the time of diagnosis. These patients were compared with a matched control group of 272 breast cancer patients who had not undergone prior hormone replacement therapy. RESULTS: Patients who developed breast cancer during hormone replacement therapy had fewer locally advanced cancers (large tumors and extensive lymph node involvement) and more well-differentiated cancers (infiltrating lobular cancers and grade 1 cancer). The number of patients with estradiol or progesterone receptors was lower in the hormone-treated group. Metastasis-free survival curves showed a tendency (P = .05) for better prognosis in hormone-treated patients both overall and in stage T2. CONCLUSIONS: Hormone replacement therapy per se does not affect the prognosis of breast cancer. Regular surveillance during hormone replacement therapy reduces the number of locally advanced cancers and thus improves the survival rate. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones. PMID- 7800306 TI - Needle modifications for invasive fetal procedures. AB - OBJECTIVE: To investigate the effect of needle size and siliconization on fetal blood sampling, transfusion, and electrocardiography. METHODS: Standard needles were modified by increasing the internal (but not the external) diameter and either siliconization of the bore or external Teflon coating. The siliconized needles were subjected to a series of flow experiments with either blood or saline at various driving pressures, and assessed in clinical use during fetal transfusion and fetal blood sampling. The Teflon-coated needles were used for fetal transfusion to try and facilitate the fetal electrocardiogram (ECG). RESULTS: Under conditions simulating fetal transfusion, the siliconized needle allowed a 93% increase in flow rate compared to the standard needle (P < .05). Samples obtained after fetal transfusion with the siliconized needles were free of clots, whereas 50% of the post-transfusion samples with the standard needle had clots present. Similarly, samples taken for fetal platelet count were free of platelet clumping and clots with siliconized needles, but not with standard needles. Fetal ECG recordings were recorded successfully when Teflon-coated needles were used to access the fetal circulation via the intrahepatic vein. CONCLUSIONS: Modifications to standard needles improved blood flow and reduced the activation of coagulation during both fetal intravascular transfusion and platelet count measurement. Direct fetal ECG recording was facilitated by Teflon coating the external surface of the needle, insulating the fetal signal from maternal electrical signals. PMID- 7800307 TI - Effect of dehydroepiandrosterone sulfate on uterine artery flow velocity waveforms in term pregnancy. AB - OBJECTIVE: To investigate the interrelation between estrogen synthesis by the fetoplacental unit and uteroplacental hemodynamics in term pregnancy. METHODS: Transvaginal color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on ten normal full-term pregnant women before and 3, 5, 10, 30, and 60 minutes after the administration of a 200-mg intravenous dose of dehydroepiandrosterone sulfate (DHAS) in 20 mL of 5% dextrose. Ten normal full term pregnant women received 20 mL of 5% dextrose as controls. The pulsatility index (PI) values for the uterine artery, heart rate, and mean arterial pressure were recorded. Plasma estradiol (E2) was measured before and 10 minutes after the infusion. RESULTS: In the DHAS group, uterine artery PI decreased from baseline by 26% (P < .05) after 5 minutes, and the mean reduction was 36% (P < .05) after 10 minutes and 15% (P < .05) after 30 minutes. The PI returned to the baseline value 60 minutes later. In the control group, there was no change in uterine artery PI. No change was found in heart rate or mean arterial blood pressure in the control or DHAS groups. The mean plasma E2 increased from 22.3 +/- 6.6 to 56.2 +/- 24.1 ng/mL (P < .05) 10 minutes after the infusion in DHAS subjects, whereas there was no significant change in plasma E2 in the controls. CONCLUSION: Dehydroepiandrosterone sulfate induces a significant decrease in the uterine artery PI, which suggests a possible decrease in uterine vascular impedance in term pregnancy. PMID- 7800308 TI - Fetal venous, arterial, and intracardiac blood flows in red blood cell isoimmunization. AB - OBJECTIVE: To investigate the effect of anemia on fetal venous, arterial, and intracardiac blood flows. METHODS: Color flow Doppler was used to record flow velocity waveforms from the atrioventricular valves, ductus venosus, right hepatic vein, inferior vena cava, middle cerebral artery, and descending thoracic aorta from 38 cases of red blood cell isoimmunized pregnancies. Immediately after the Doppler studies, funipuncture was performed and the fetal hemoglobin concentration was measured. RESULTS: Blood flow velocities in the thoracic aorta, middle cerebral artery, and the ductus venosus were increased compared to reference ranges established previously; however, a significant association with the degree of anemia was found only for the velocity in the thoracic aorta. Pulsatility indices in arteries and veins and the ratio of early to late atrioventricular inflow velocities were not significantly different from normal. CONCLUSIONS: Fetal anemia is associated with a hyperdynamic circulation in both arterial and venous vessels. Even in severe anemia, there is no evidence of congestive heart failure. Venous and intracardiac Doppler studies do not provide a clinically useful contribution in the management of red blood cell isoimmunization. PMID- 7800309 TI - Laparoscopically assisted vaginal removal of ovarian dermoid cysts. AB - Dermoid cysts were diagnosed by transvaginal sonography in 19 patients who subsequently underwent laparoscopy to confirm the nature and extent of the lesion and the mobility of the adnexa. Eighteen patients underwent surgery after the ovary was exteriorized through a posterior colpoceliotomy. No intraoperative complications were observed, and sonographic follow-up at 3 and 6 months after surgery showed a normal sonographic ovarian pattern. Laparoscopically assisted vaginal removal of dermoid cysts should be considered as an alternative to laparotomy and operative laparoscopy in cases when adnexal mobility is proven and vaginal extraction is feasible. PMID- 7800310 TI - Transumbilical placement of the vaginal probe in obese pregnant women. AB - Transabdominal ultrasonography in obese pregnant women is often unsatisfactory because of the poor transmission of ultrasound through a thickened abdominal wall. We report our experience with the placement of a transvaginal probe in the umbilicus to improve resolution in obese pregnant patients. The technique, which involves filling the umbilicus with ultrasound transmission gel and inserting the transvaginal probe into the umbilicus, was applied in 25 consecutive obese patients who had unsatisfactory fetal imaging by the standard transabdominal approach. The most frequent reason for incomplete fetal survey by the standard transabdominal approach was unsatisfactory imaging of the fetal heart (19 of 25 cases, 76%). The transumbilical approach resulted in improved resolution and satisfactory cardiac examination in 18 of these 19 cases (95%). In two cases, color and pulsed Doppler interrogation of intrafetal vessels become possible. A complete fetal survey was accomplished in 96% of the cases. PMID- 7800311 TI - Interactive multimedia for prenatal ultrasound training. AB - This demonstration project examines the utility of interactive multimedia for prenatal ultrasound training. A laser-disc library was linked to a three dimensional (3-D) heart model and other computer-based training materials through interactive multimedia. A testing module presented ultrasound anomalies and related questions to house-staff physicians through the image library. Users were asked to evaluate these training materials on the basis of perceived instructional value, question content, subjects covered, graphics interface, and ease of use; users were also asked for their comments. House-staff physicians indicated that they consider interactive multimedia to be a helpful adjunct to their core fetal imaging rotation. During a 9-month period, 16 house-staff physicians correctly diagnosed 78 +/- 4% of unknown cases presented through the testing module. The 3-D heart model was also perceived to be a useful teaching aid for spatial orientation skills. Our findings suggest that interactive multimedia and volume visualization models can be used to supplement traditional prenatal ultrasound training. The system provides a broad exposure to ultrasound anomalies, increases opportunities for postnatal correlation, emphasizes motion video for ultrasound training, encourages development of independent diagnostic ability, and helps physicians understand anatomic orientation. We hypothesize that interactive multimedia-based tutorials provide a better overall training experience for house-staff physicians. However, these supplementary methods will require formal evaluation of effectiveness to better understand their potential educational impact. PMID- 7800312 TI - Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. AB - OBJECTIVE: To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. DATA SOURCES: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English language articles on first-trimester sex-hormone exposure and fetal genital changes. METHODS OF STUDY SELECTION: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. DATA EXTRACTION AND SYNTHESIS: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24 3.94). CONCLUSION: There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation. PMID- 7800313 TI - Intrapartum electronic fetal heart rate monitoring versus intermittent auscultation: a meta-analysis. AB - OBJECTIVE: To use a meta-analysis of all published randomized trials to determine whether the use of continuous electronic fetal heart rate monitoring (EFM) as the main method of intrapartum fetal surveillance is associated with improved pregnancy outcome compared to intermittent auscultation. DATA SOURCES: We used the MEDLINE data base and reference lists of articles to identify all published randomized trials of EFM versus intermittent auscultation. METHODS OF STUDY SELECTION: A total of nine randomized trials published in peer-review journals were identified. The selection criterion was the use of EFM or intermittent auscultation as the main intrapartum fetal surveillance technique. DATA EXTRACTION AND SYNTHESIS: A total of 18,561 patients were included in the nine published randomized trials, 9398 in the EFM group and 9163 in the auscultation group. Measures of pregnancy outcome included cesarean delivery, cesarean for suspected fetal distress, overall use of forceps or vacuum, use of forceps or vacuum for suspected fetal distress, overall perinatal mortality, and perinatal mortality due to fetal hypoxia (intrapartum or early neonatal death) attributable to the method of intrapartum monitoring. The meta-analysis showed that the patients monitored electronically had a significantly higher overall cesarean rate (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.17-2.01), higher cesarean rate for fetal distress (OR 2.55, 95% CI 1.81-3.53), overall increased use of forceps or vacuum (OR 1.23, 95% CI 1.02-1.49), increased use of forceps or vacuum for suspected fetal distress (OR 2.50, 95% CI 1.97-3.18), and decreased perinatal mortality due to fetal hypoxia (OR 0.41, 95% CI 0.17-0.98). CONCLUSION: Electronic fetal monitoring is associated with increased rates of surgical intervention and decreased perinatal mortality due to fetal hypoxia. PMID- 7800314 TI - Acupressure for nausea and vomiting of pregnancy: a randomized, blinded study. PMID- 7800315 TI - Prevention of neonatal group B streptococcal infection. PMID- 7800316 TI - The risk of repeating low birth weight and the role of prenatal care. PMID- 7800318 TI - Six hundred endometrial laser ablations. AB - OBJECTIVE: To report the effectiveness and safety of endometrial laser ablation in the treatment of menorrhagia, as determined by detailed follow-up of 600 operations for at least 6 months. METHODS: Operative data from 600 endometrial laser ablations performed on 524 women were collected. Five hundred one (96%) of these women were followed with consultations and questionnaires. The mean duration of follow-up was 15 months (range 6-42). RESULTS: No major operative morbidity occurred. There were no cases of primary or secondary hemorrhage, uterine perforations with the operating instrument, or immediate laparotomy. A successful outcome was reported by 83.4% of patients. A second endometrial laser ablation was required in 14.3% of the women. Success increased with increasing age and low fluid absorption. Cavity length, operation time, duration of follow up, and whether it was a first or second procedure were not associated with any difference in the success rate, although the hysterectomy rate tended to rise with increasing length of follow-up. CONCLUSION: This study, the largest one published from a single institution, with a mean follow-up duration of 15 months, confirms that endometrial laser ablation is a safe and effective treatment for dysfunctional uterine bleeding. PMID- 7800317 TI - Guidelines to determine the route of hysterectomy. AB - OBJECTIVE: To 1) test the validity of a method of assigning patients prospectively to a vaginal, abdominal, or laparoscopy-assisted vaginal approach to hysterectomy for benign disease; 2) compare the outcomes of these options from the day of surgery to the first day of returning to normal activities; and 3) estimate the proportion of hysterectomies by each route when patients were assigned according to this system, and the impact on hospital charges. METHODS: Six hundred seventeen women were assigned to a route of hysterectomy on the basis of uterine size (greater or less than 280 g), presumptive risk factors, and uterine or adnexal immobility or inaccessibility. Data regarding the success of the procedure, complications, length of hospital stay and convalescence, and hospital charges were compiled. RESULTS: Vaginal hysterectomy alone (n = 548) or in conjunction with laparoscopy (n = 63) was successful in 99.5% of women assigned to these groups. Patients in whom the vaginal route was successful included 94% of those with uterine weights exceeding 280 g and 97% of those having risk factors often cited as reasons for selecting abdominal hysterectomy. Laparoscopic surgery was necessary to permit a transvaginal operation in only 12 of 63 patients (19%). Use of the guidelines produced a potential savings of 615 hospital days, $1,317,434 in hospital charges, and 7250 convalescent days relative to the 3:1 ratio of abdominal to vaginal hysterectomies prevalent in the United States. CONCLUSIONS: Specific guidelines for uterine size, risk factors, and uterine and adnexal mobility and accessibility are useful in selecting the operative approach to hysterectomy and will significantly reduce the number of abdominal operations performed. Laparoscopy is valuable in properly selected patients to determine the route of hysterectomy, but the need for laparoscopic techniques to permit a vaginal operation may be considerably less than some investigators have proposed. PMID- 7800319 TI - Synthetic hygroscopic cervical dilator use in patients with unsatisfactory colposcopy. AB - OBJECTIVE: To assess the ability of a synthetic hygroscopic cervical dilator to make an unsatisfactory colposcopic examination satisfactory, thereby avoiding cervical conization. MATERIALS: From April 1991 to March 1993, 30 women with unsatisfactory colposcopic examinations underwent repeat colposcopy after a synthetic hygroscopic cervical dilator had been placed in the endocervical canal for approximately 2 hours. RESULTS: The reasons for initial unsatisfactory colposcopy in the 30 patients were squamocolumnar junction not seen in its entirety (18 patients, 60%), lesion not seen in its entirety (ten, 33%), and neither transformation zone nor lesion seen in their entirety (two, 7%). Complications were encountered in one patient from whom the dilator could not be removed completely. Of 29 patients undergoing repeat colposcopy, 23 (79%) had satisfactory examinations. In 15 of 30 patients, conization was avoided; it was required in six of 30 (20%) women for persistent unsatisfactory colposcopy (including the patient in whom the dilator broke) and in nine of 30 (30%) for other indications. CONCLUSIONS: This experience suggests that a synthetic hygroscopic cervical dilator can be used in patients with an unsatisfactory colposcopy to achieve a satisfactory examination, thus avoiding cervical conization. PMID- 7800320 TI - Localization of blood vessels and qualitative assessment of blood flow in ovarian tumors. AB - OBJECTIVE: To study the localization of blood vessels within a tumor and the shape of the flow curve as a method of assessing ovarian neoplasms. METHODS: We studied 39 patients with malignant tumors and 63 patients with benign ovarian tumors by means of vaginal color Doppler ultrasound, noting the localization of blood vessels in the tumors, the shape of the flow curve, and peripheral resistance. RESULTS: Blood vessels could be visualized in 95% of the malignant tumors and in 70% of the benign tumors. Blood vessels tended to be localized centrally (65 versus 5%) in malignant tumors and peripherally in benign tumors (65 versus 0%). A diastolic notch was seen in 89% of the benign tumors, but in none of the malignant tumors. The mean resistance index (RI) +/- standard deviation was 0.48 +/- 0.19 in malignant and 0.69 +/- 0.09 in benign tumors (P < .05). The corresponding values for the pulsatility index (PI) were 0.56 +/- 0.13 and 1.06 +/- 0.07, respectively (P < .01). CONCLUSIONS: Low RI and PI values are general indicators of tumor growth. The localization of blood vessels within an ovarian tumor and the presence or absence of a diastolic notch are the most useful variables in the evaluation of ovarian tumors. PMID- 7800321 TI - Prognostic significance of morphologic changes of the corpus luteum by transvaginal ultrasound in early pregnancy monitoring. AB - OBJECTIVE: To determine whether the ultrasound appearance, size, or change in size of the corpus luteum of early pregnancy correlated with serum progesterone, estradiol (E2), or 17-hydroxyprogesterone or were predictive of pregnancy outcome. METHODS: Transvaginal ultrasound assessment of the corpus luteum was performed prospectively on 55 women between 4-8 weeks' gestation. Forty-five (82%) subjects conceived in spontaneous cycles and ten (18%) conceived in cycles stimulated with clomiphene citrate. Fifty-three of 55 (96.4%) women had a second ultrasound assessment 5-8 days later (mean 6.7). Blood was drawn from each patient on the day of the ultrasound examination to measure hormone concentration. RESULTS: The appearance of the corpus luteum (macrocystic [more than 50% cystic], microcystic [less than 50% cystic], or noncystic) was not predictive of hormone concentration or pregnancy outcome. A nonviable pregnancy occurred in five of six (83%) women in whom a corpus luteum was undetectable by ultrasound and in 15 of 49 (31%) women in whom a corpus luteum was present (P = .01). There was no specific corpus luteum volume which could predict pregnancy failure. However, when a decreasing volume from first to second ultrasound examination was observed, 11 of 20 (55%) pregnancies resulted in nonviable outcomes compared to five of 27 (19%) when an increasing volume was observed (P < .01). There was no significant positive correlation between corpus luteum volume and plasma progesterone or 17-hydroxyprogesterone. A weak correlation was observed between corpus luteum volume and E2 (r = 0.38, P = .04). CONCLUSIONS: Our data reveal a lack of correlation between the size of the corpus luteum on ultrasound examination and known steroid products in pregnancies conceived during spontaneous cycles. Corpus luteum volume and steroid products were higher in those patients whose ovulation was induced with clomiphene citrate. Also, different morphologic appearances of the corpus luteum in early human pregnancy, based on the amount of cystic component, have no functional significance. However, a decreasing corpus luteum volume before 8 weeks' gestation is associated with a higher probability of early pregnancy loss. PMID- 7800322 TI - Transabdominal sonohysterography, transvaginal sonography, and hysteroscopy in the evaluation of submucous myomas. AB - OBJECTIVE: To assess the usefulness of transabdominal sonohysterography in the diagnosis and evaluation of submucous myomas. METHODS: Fifty-two premenopausal women hospitalized for hysterectomy for benign gynecologic indications underwent preoperative conventional transvaginal sonography, transabdominal sonohysterography, and hysteroscopy. The results of the three techniques in terms of diagnosis, size, intracavitary growth, and location of the submucous myomas were compared with those revealed by direct inspection of the surgical specimens. RESULTS: Conventional transvaginal sonography for the diagnosis of submucous myomas had a sensitivity of 90% and a specificity of 98%; the predictive values of abnormal and normal scans were 90 and 98%, respectively. Transabdominal sonohysterography had sensitivity, specificity, and predictive values of 100%, as did hysteroscopy. In all cases, the sonographic techniques measured tumor size more accurately than did hysteroscopy. The transabdominal sonohysterography measurements differed from direct evaluation by no more than 2 mm, and the hysteroscopic measurements were significantly different from those of the surgical specimens. The sonohysterographic evaluation of intrauterine growth was significantly more precise than that of the other techniques, differing from direct measurements by no more than 5-10%. Conventional transvaginal sonography failed to localize three of 11 myomas; hysteroscopy and transabdominal sonohysterography provided the exact location in all cases. CONCLUSION: Transabdominal sonohysterography is the most accurate technique for detecting submucous myomas and evaluating their size, intracavitary growth, and location. PMID- 7800323 TI - Transvaginal ultrasonography in the diagnosis of cystic teratoma. AB - OBJECTIVE: To assess prospectively the role of transvaginal ultrasonography in screening for cystic teratoma and in differentiating cystic teratoma from other ovarian masses. METHODS: Three hundred seventy-six premenopausal non-pregnant women underwent transvaginal ultrasonography 1 week before undergoing laparotomy or laparoscopy. The visualization of localized or diffuse echogenicity was chosen as the characteristic ultrasonographic finding of cystic teratoma. Endosonographic diagnosis was compared with surgical and pathologic findings. RESULTS: Sensitivity and specificity for the ultrasonographic screening were 57.9 and 99.7%, respectively, calculated for each visualized ovary (n = 659), and 84.6 and 98.2%, respectively, for differentiating cystic teratoma from other ovarian masses, calculated for each visualized cyst (n = 123). CONCLUSION: Transvaginal ultrasonography has a better predictive ability for differentiating cystic teratoma from other ovarian masses (kappa value 0.84) than in screening for cystic teratomas (kappa value 0.69). PMID- 7800324 TI - Use of the APACHE II scoring system to determine mortality of gynecologic oncology patients in the intensive care unit. AB - OBJECTIVE: To determine if an elevated score on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is associated with mortality of acutely ill gynecologic oncology patients. METHODS: Gynecologic oncology patients admitted to the surgical intensive care unit (ICU) were identified from the ICU data base. Their admission APACHE II score and type of gynecologic cancer were also extracted from the data base. Charts were reviewed to determine the disease status and reason for admission to the surgical ICU. Patient mortality was correlated with APACHE II scores. RESULTS: Forty-five gynecologic oncology patients were admitted to the surgical ICU from June 1988 to January 1992. They had a mean age of 62 years and various cancers: ovarian (24), cervical (16), and endometrial (five). The mean APACHE II score was 12 (range 2-26). Eight of 45 (18%) patients died. There was a significant correlation between APACHE II scores and mortality; patients with an APACHE II score of 20 or greater had a 78% risk of death compared to a 3% risk if the score was less than 20 (P < .001, chi 2 test). CONCLUSION: Elevated APACHE II scores are associated with mortality in acutely ill gynecologic oncology patients. PMID- 7800325 TI - Developmental potential of microbiopsied murine blastocysts. AB - OBJECTIVE: To evaluate the frequency of mouse pups born following blastocyst biopsy and embryo transfer compared to nonbiopsied controls. METHODS: ICR Swiss albino and C57B1/6 mice served as embryo donors. Pregnant mare serum gonadotropin treatment was followed 46-52 hours later by hCG, when donors were paired with fertile males. Mating was confirmed the following day and embryos were collected on the afternoon of day 4. After overnight culture, hatching trophoblast was excised by micromanipulation with a fine-pulled glass pipette. Embryos (206 controls, 206 biopsied) were transferred to 26 pseudopregnant recipients. Alternate mouse strains were used to identify pups born from control or biopsied embryos. RESULTS: The end point was percentage of pups born ((number born/number transferred) x 100), using angular transformation before analysis. There was no significant difference (P > .1) between percent live-born in control (27.7%) or biopsied (34.5%) embryos, nor were there any strain differences. CONCLUSION: These data support the hypothesis that the developmental potential of murine blastocysts is not affected adversely by the biopsy procedure. PMID- 7800326 TI - Use of menopausal estrogens and medroxyprogesterone in the United States, 1982 1992. AB - OBJECTIVE: To describe trends in the prescription of menopausal estrogens and medroxyprogesterone in the United States. METHODS: Annual estimates of the number of prescriptions for menopausal estrogens and medroxyprogesterone and descriptive information on patients and providers were obtained from two pharmaceutical marketing research data bases, the National Prescription Audit and the National Disease and Therapeutic Index of IMS America. RESULTS: An estimated 13.6 million prescriptions were dispensed for oral menopausal estrogens in 1982, and 31.7 million in 1992, a 2.3-fold increase (P = .0001). In 1992, Premarin, the only oral conjugated estrogen currently approved for use, was the most frequently dispensed brand-name pharmaceutical in the United States. Dispensed prescriptions for Estraderm, a transdermal estradiol first marketed in 1986, increased from 1.5 million in 1987 to 4.7 million in 1992. Dispensed prescriptions for oral medroxyprogesterone also increased from 2.3 million prescriptions in 1982 to 11.3 million in 1992, a 4.9-fold increase (P = .0001). An estimated one in six to one in four postmenopausal women were taking menopausal hormones in 1992. These drugs were prescribed mainly by obstetrician-gynecologists. CONCLUSION: The use of menopausal estrogens and medroxyprogesterone has increased substantially over the past decade. These trends indicate that American women are widely exposed to menopausal hormone replacement. PMID- 7800327 TI - Maternal serum uric acid levels in twin gestations. AB - OBJECTIVE: To establish normative values of serum uric acid levels in women with twin gestations and to compare maternal serum uric acid levels of twins and singletons, stratified by the presence or absence of preeclampsia. METHODS: Sixty seven normotensive and 16 preeclamptic women with twin gestations, who had no underlying chronic hypertension or renal insufficiency, had serum uric acid levels measured on admission to the labor and delivery unit. These levels were compared with those of 83 normotensive and 10 preeclamptic singleton gravidas admitted to the same unit. A receiver operating characteristic (ROC) curve was used to determine the optimal maternal serum uric acid cutoff value for twin gestations and to compare this value with that of singleton gestations. RESULTS: Women with non-preeclamptic twin pregnancies had significantly higher mean (+/- standard deviation) serum uric acid concentration than women with non preeclamptic singleton pregnancies (5.4 +/- 1.6 versus 4.7 +/- 1.2 mg/dL, respectively, P = .001). Gravidas with twin gestations complicated by preeclampsia had significantly higher serum uric acid levels than their preeclamptic singleton counterparts (7.7 +/- 1.3 versus 5.9 +/- 1.1 mg/dL, respectively, P = .001). Using a ROC curve, we determined that a maternal serum uric acid level of 6.5 mg/dL appeared to be the optimal cutoff for identifying preeclampsia in twin gestations, with a sensitivity of 94% and specificity of 78%. CONCLUSION: With or without preeclampsia, women carrying twins have significantly higher serum uric acid levels than their singleton counterparts, which suggests a need for separate normative values for twin gestations. We propose that a serum uric acid level of 6.5 mg/dL or greater be used to identify those women with twin gestations who are at higher risk for preeclampsia. PMID- 7800328 TI - Pregnancy outcome in nulliparous women 35 years and older. AB - OBJECTIVE: To compare pregnancy and delivery complications of first births in women 35 years and older with women 25-29 years old. METHODS: Maternal and newborn records for first births at three suburban hospitals from July 1, 1986 to June 30, 1990 were studied retrospectively. RESULTS: The older women differed significantly in: 1) antepartum factors (type of insurance, marital status, prior pregnancy experience, weight gain, obesity, chronic and pregnancy-induced hypertension, gestational diabetes [without insulin], asthma, leiomyomas; and third-trimester bleeding), 2) intrapartum factors (anesthesia for vaginal delivery, gestational age at delivery, preterm labor, spontaneous labor, oxytocin use, malpresentation, cesarean births, and postpartum hemorrhage), and 3) neonatal outcomes (gestational age, birth weight, preterm births, abnormal karyotypes, neonatal intensive care unit admissions, low birth weight, and small for gestational age infants). Logistic regression determined that risk factors significantly predicting perinatal mortality were leiomyomas (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.3-5.0), preterm birth (OR 4.9, 95% CI 3.1 7.7), and chorioamnionitis (OR 5.9, 95% CI 3.1-11.4), but not age. CONCLUSION: Nulliparous women 35 years and older had higher rates of antepartum, intrapartum, and newborn complications than nulliparas between the ages of 25-29 years, but not an increased perinatal mortality rate. Despite the increased risk of complications, maternal and perinatal outcomes were good. PMID- 7800329 TI - A randomized trial of management of pre-labor rupture of membranes at term in multiparous women using vaginal prostaglandin gel. AB - OBJECTIVE: To compare conservative management of pre-labor spontaneous rupture of membranes (SROM) with the use of prostaglandin (PG) E2 in healthy parous women at term (gestational age at least 37 weeks). METHODS: An open randomized study was conducted with 100 parous women; 50 were treated conservatively for 24 hours, and 50 were managed actively using PGE2 gel (1 mg), administered at admission and repeated 6 hours later if labor was not established. Both groups received intravenous oxytocin if labor did not start within 24 hours after admission. RESULTS: The use of PGE2 gel led to a significant reduction in the mean interval (+/- standard error of the mean) from SROM to onset of labor: 17.26 +/- 1.51 hours in the conservative group versus 6.50 +/- 1.23 in the PGE2 group. A significantly smaller proportion of subjects required oxytocin in the PGE2 group (12 versus 38%, P < .02). The two groups were comparable with respect to analgesic requirements. Within 24 hours of SROM, 80% of the women in the PG group and 56% in the conservative group had delivered (P < .02). Most women delivered vaginally, 96% of those managed conservatively and 100% of those managed actively with PGE2. CONCLUSION: Active management using PGE2 gel in parous women with pre labor SROM significantly improves the time to delivery without influencing the cesarean rate or fetal-maternal infective morbidity. PMID- 7800330 TI - Fetal acidemia associated with regional anesthesia for elective cesarean delivery. AB - OBJECTIVE: To determine the prevalence, magnitude, and type of fetal acidemia associated with contemporary obstetric anesthetic techniques. METHODS: Umbilical artery blood gases were obtained in 1601 singleton pregnancies delivered by elective cesarean. RESULTS: General anesthesia was used in 371 (23%) women, epidural in 286 (18%), combined spinal-epidural in 659 (41%), and spinal in 231 (14%). Approximately 18% of infants exposed to regional anesthetics had umbilical artery blood pH values 7.19 or less, 42 (3%) infants had pH values less than 7.10, and nine (1%) had values 6.99 or less. The incidence of fetal acidemia was greater in spinal and combined spinal-epidural procedures compared to epidural anesthetics. Fetal acidemia was predominantly respiratory in type because carbon dioxide pressure was abnormally increased when fetal acidemia was diagnosed. CONCLUSIONS: Regional anesthesia is associated with fetal acidemia, occasionally severe, and has features of an acute respiratory type of acidemia. Fetal acidemia is less frequent with epidural anesthesia compared to subarachnoid techniques. PMID- 7800331 TI - Limb defects after chorionic villus sampling. AB - OBJECTIVE: To clarify the association between limb defects and chorionic villus sampling (CVS). METHODS: Questionnaires were sent to 165 major obstetric units in Taiwan to survey the incidence of limb defects with and without CVS exposure during 1991. Limb defects with CVS exposure from September 1990 to June 1992 were also surveyed. The spectrum of limb defects in CVS-exposed and general populations were compared by the Poisson test. RESULTS: The incidence of limb defects in the surveyed general population in 1991 was 0.032% and that with CVS exposure was 0.294%, a statistically significant difference (P < .001). The incidence of severe limb defects in the general population was 0.0026% and that with CVS exposure was 0.22%, also statistically significant (P < .001). Twenty nine cases of limb defects after CVS were reported from September 1990 until June 1992: 19 cases with transverse limb reduction, two with mid-palm reduction, seven with adactyly or hypodactyly, and one with syndactyly. Four cases also had oromandibular-limb hypogenesis syndrome. CONCLUSIONS: The incidence of limb defects, especially the severe types, was increased after CVS. The spectrum of limb defects with CVS exposure was more severe than the limb defects seen in the general population and showed a specific pattern ranging from hypodactyly, adactyly, and transverse limb reduction, to oromandibular-limb hypogenesis. A correlation between the severity of limb defects and the timing of CVS was suggested. PMID- 7800332 TI - Aggressive intrapartum management of lethal fetal anomalies: beyond fetal beneficence. AB - OBJECTIVE: To evaluate management recommendations from the current literature for patients whose fetuses are certain to have lethal anomalies or absent (or virtually absent) cognitive function. These recommendations include termination of pregnancy or, for cases in the third trimester, nonaggressive intrapartum management, avoiding cesarean delivery for fetal indications. METHODS: We report our experience with several patients who voiced opposition to nonaggressive intrapartum care and present a rationale for selectively aggressive, intrapartum management for some of these cases. RESULTS: Four women whose fetuses had lethal anomalies requested aggressive intrapartum management. For three of the four, standard aggressive management of labor resulted in vaginal delivery of live-born infants who died shortly thereafter. The patients found comfort in the live births. The fourth patient accepted a recommendation to avoid fetal monitoring during labor, and the fetus was stillborn. This patient found the intrapartum experience to be very stressful. CONCLUSION: When a patient's desire to avoid an intrapartum stillbirth is strong enough that substantial psychological harm might result from one, the physician's beneficence-based obligation to her and respect for maternal autonomy justify selectively aggressive intrapartum therapy, even if no beneficence-based obligation to the fetus exists. PMID- 7800333 TI - Characterization of the effect of cocaine on catecholamine uptake by pregnant myometrium. AB - OBJECTIVE: To characterize the effect of cocaine on catecholamine uptake by myometrium from pregnant women. METHODS: Slices of myometrium obtained from nine women during elective cesarean delivery at term were incubated with [3H] norepinephrine and various uptake inhibitors for 30 minutes. The radiolabeled material was extracted with perchloric acid, expressed as percent control (+/- standard error of the mean), and compared by one-factor analysis of variance and Fisher multiple range test. RESULTS: Myometrial uptake was inhibited by cocaine (42 +/- 9%) by neuronal (type 1) uptake inhibitors (desipramine 41 +/- 14%; N ethylmaleimide 53 +/- 8%), and by extraneuronal (type 2) inhibitors (normetanephrine 56 +/- 19%; corticosterone 73 +/- 9%). When uptake inhibitors were used in combination with cocaine, uptake was not decreased further in the presence of neuronal inhibitors (desipramine plus cocaine 40 +/- 20%; N ethylmaleimide plus cocaine 42 +/- 4%). However, the effect of cocaine appeared to be added to that of extraneuronal inhibitors (normetanephrine plus cocaine 25 +/- 14%; corticosterone plus cocaine 32 +/- 1%). CONCLUSION: Catecholamine uptake by myometrium in pregnant women appears to be both extraneuronal and neuronal in nature, and cocaine inhibits the neuronal portion of this uptake. This mechanism may play a role in the increased rate of premature delivery associated with cocaine abuse. PMID- 7800334 TI - Levorotation of the fetal cardiac axis: a clue for the presence of congenital heart disease. AB - OBJECTIVE: To evaluate the use of the cardiac axis within the chest for the prenatal detection of congenital heart defects. METHODS: We reviewed retrospectively the sonographic findings of all fetuses scanned between 17 and 40 weeks' gestation and diagnosed prenatally as having heart defects. The cardiac diagnoses were confirmed postnatally. The control group consisted of 75 consecutive fetuses with normal fetal surveys and newborn follow-up examinations. The cardiac axes were measured retrospectively using an image of the four-chamber view of the heart and measuring the angle between the interventricular septum and a line bisecting the chest. Mean and standard deviations (SDs) of the axis measurements in normal and abnormal fetuses were compared by Student t test. RESULTS: The 75 fetuses with heart defects diagnosed by prenatal sonogram had a mean cardiac axis of 56 +/- 13 degrees, compared with 43 +/- 7 degrees in normal fetuses (P < .001). Using 57 degrees (two SDs above the mean for normal fetuses) as the upper limit of normal, 33 of 75 (44%) abnormal fetuses versus none of 75 normal fetuses were identified. The frequency of cardiac rotation was greater in fetuses with truncus arteriosus, Ebstein's anomaly, pulmonic stenosis, coarctation of the aorta, and tetralogy of Fallot. CONCLUSION: The presence of a cardiac axis exceeding 57 degrees in the fetal chest is associated with a substantial risk of congenital heart defects. The finding of an abnormal axis should prompt further evaluation of the fetal heart. PMID- 7800335 TI - Modulation of CD4 antigen expression on the lymphocyte surface by immunosuppressive acidic protein in cancer patients. AB - The immunomodulatory effect of human immunosuppressive acidic protein (IAP) on lymphocyte surface antigens was investigated. IAP inhibited lymphocyte responses to phytohemagglutinin in a dose-dependent manner. By flow cytometry, using fluorescein-isothiocyanate-labelled antibodies, the mean fluorescence intensity on peripheral blood lymphocytes (PBLs) decreased for CD4, slightly decreased for CD3 but showed no change for the CD8 and T cell receptor alpha-beta antigens in the presence of IAP. This CD4 antigen modulation by IAP was observed in PBLs freshly isolated from patients with unresectable cancer but not in those isolated from patients with resectable tumor or from healthy volunteers. The modulation of the CD4 antigen by IAP on the lymphocyte surface was correlated with an increment of serum IAP levels in cancer patients. The CD4 modulation could be induced in PBLs from healthy volunteers by culturing them with IAP in vitro. It is suggested that IAP may play a role in cancer-related immunosuppression through the down modulation of the CD4 antigen on the lymphocyte surface. PMID- 7800336 TI - Leukocyte alkaline phosphatase as a probable predictor of the metastatic state in breast and colon cancer patients. AB - Leukocyte alkaline phosphatase (LAP) score in peripheral blood was determined in 45 new cancer patients, 30 with breast cancer and 15 with colorectal cancer, with nonmetastatic disease. The LAP scores were performed immediately after diagnosis or surgery, and later at intervals of 1-3 months, until clinical detection of metastases. The preliminary data presented here show that there may be some utility in measuring LAP score in patients with solid tumors on a serial basis to detect evidence of metastatic disease prior to its clinical recognition. In 22 out of 30 breast cancer patients and 11 out of 15 colon cancer patients, there were 'alarming signals' of metastases (defined in this study) in the data taken before the checkup in which metastases were diagnosed by other methods. We conclude that LAP scores should be introduced into routine checkup of breast and colon cancer patients and could be a helpful nonspecific additional element in detecting earlier metastatic disease during the follow-up of a patient. As an extrapolation from this study we suggest that work should be undertaken to explore the possibility that a sudden rise of LAP score in an otherwise healthy person, who has no known reason for an elevated LAP score, might be the very first measurable sign of cancer. PMID- 7800337 TI - Is CA242 really a new tumour marker for pancreatic adenocarcinoma? AB - CA 242, a sialylated carbohydrate epitope situated on the same macromolecule as CA 50 has been proposed as a new tumour marker for pancreatic cancer (PC). The aims of the present study were: (1) to evaluate serum CA 242 versus CA 19-9 in PC patients, and (2) to assess whether these markers can predict tumour spread or patient survival. We studied 59 healthy controls, 27 PC patients, 12 chronic pancreatitis cases, 107 with extra-pancreatic gastrointestinal tumours, 30 with benign jaundice and 24 with benign extra-pancreatic gastrointestinal diseases. Mean CA 242 values were significantly higher in PC than in any other group; CA 19 9 showed a similar pattern. The best diagnostic efficacy (ROC curves analysis) in diagnosing PC was 86% for CA 242 and 84% for CA 19-9, using cut-off values of 60 and 80 U/ml, respectively. In PC, serum levels of both markers were unrelated to tumour spread or size; in PC patients with high levels of CA 242 or CA 19-9 survival was significantly shorter. CA 242 and CA 19-9 were correlated both when considering all the patients together (r = 0.962, p < 0.001) and PC alone (r = 0.880, p < 0.001). Given the very close relationship between CA 242 and CA 19-9, we tested for cross-reactivity between CA 242 antigen and CA 19-9 antibody: CA 242 antigen with CA 19-9 antibody produced a similar curve to CA 242 antigen and its corresponding antibody. In conclusion, CA 242 showed similar diagnostic values to CA 19-9 in assessing PC patients; both seem unrelated to tumour size or spread, but seem to predict survival. Their remarkably similar behaviour is due to cross-reactivity between CA 242 antigen and CA 19-9 antibody, so CA 242 cannot, in our opinion, be considered a new tumour marker for PC. PMID- 7800338 TI - Treatment of non-small cell lung cancer with ifosfamide (IFO)+ 4'-epiadriamycin (EPI)+platinum vs. IFO+EPI: a GETLAC Study. Grupo de Estudio y Tratamiento Latinoamericano del Cancer Study. AB - 203 patients with inoperable non-small cell lung cancer (NSCLC) were randomized to receive ifosfamide (IFO) 2.5 g/m2 days 1-2 + epirubicin (EPI) 70 mg/m2 day 1 with cisplatin (DDP) 70 mg/m2 day 1 (arm IEP), or without cisplatin (arm IE). For uroprophylaxis, mesna i.v. 20% of IFO dose, hour 0 and 3, and oral, 40% of IFO dose, hour 6 and 9, days 1-2 was given. Cycles were repeated every 28 days. Four cycles were required for evaluation purposes. After completion of chemotherapy, external beam irradiation 40 Gy was given over 4 weeks for stage III B responders. Most of the patients with stable disease, partial response or complete response (CR) received 6 cycles. The median follow-up of the trial is 30 months. There were no differences in overall response rates: arm IEP: 52% (2% CR); arm IE: 51% (13.5% CR). Median time to progression was 6 months (arm IEP) and 4 months (arm IE) (p = 0.4844). Toxicity ranged from mild to moderate. Nephrotoxicity was not seen; only 6 patients had neurotoxic side effects of short duration. Median survival according to treatment was 12 months for IEP arm (12% at 2 years) and 10 months for IE arm (21% at 2 years). IFO/mesna+EPI or IFO/mesna, EPI plus DDP appeared to be an active and well tolerated combination for the treatment of NSCLC, with a good survival time. PMID- 7800339 TI - Modulatory influence of the oral contraceptive pill, Ovral, on 3 methylcholanthrene-induced carcinogenesis in the uterus of mouse. AB - The present study examines the modulatory influence of the combined oral contraceptive pill, Ovral (0.05 mg ethynylestradiol plus 0.25 mg levonorgestrel per pill) on methylcholanthrene (MCA)-induced carcinogenesis in the uterus of Swiss albino mouse. Placement of cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA, yielded endometrial squamous cell carcinomas in 53.33% animals in 90 days. Concomitant treatments with doses D1 (1/200th of a pill) and D2 (1/200th of a pill) of Ovral yielded endometrial squamous cell carcinomas in 6.23 and 0% of animals in 90 days (p < 0.05; p < 0.005) respectively. Ovral did not seem to increase the incidence of uterine hyperplasia. PMID- 7800340 TI - Surgical treatment and prognosis for patients with gastric cancer lesions larger than ten centimeters in size. AB - In 323 of 1,620 patients with gastric cancer, the lesion was > or = 10 cm in maximum diameter. Studies were done with respect to clinicopathologic features and the prognosis. Patients with tumors > or = 10 cm were younger and women patients were more numerous compared to those with tumors < 10 cm. Tumors were more advanced and noncurative resection was usually done for these patients. A multivariate analysis showed that serosal invasion, liver metastasis, lymph node metastasis, operative curability, tissue differentiation, and extended lymph node dissection to be independent prognostic factors. This retrospective study showed that patients with a larger tumor are at an increased risk for tumor advancement and that they will benefit from curative resection and extended lymph node dissection. PMID- 7800341 TI - Phase II study of the etoposide, leucovorin and fluorouracil combination for patients with advanced gastric cancer unsuitable for aggressive chemotherapy. AB - Many patients with advanced gastric cancer cannot be treated with intensive chemotherapy. In an attempt to provide a feasible regimen for such patients, the combination of etoposide, leucovorin and fluorouracil (ELF) has been developed with promising results. The present study involved 42 patients with advanced gastric cancer who where unsuitable for cisplatin- or anthracycline-containing regimens because of their age (24 patients over 65 years), poor performance status (12) or the presence of concomitant illness (6). The treatment consisted of etoposide 120 mg/m2 i.v., 1-leucovorin 150 mg/m2 i.v. and fluorouracil 500 mg/m2 i.v. for 3 consecutive days every 3 weeks. Among the 41 evaluable patients, there was a 32% objective response rate (95% confidence interval 19-48%), with 7% of complete remissions. The median response duration was 4 months, the median time to progression in all patients was 5 months and the median overall survival was 10 months. No drug-related deaths or WHO grade 4 side effects were observed. On the basis of these results, we concluded that the ELF regimen is feasible and that its activity warrants randomized studies comparing the ELF combination with fluorouracil plus folinic acid. PMID- 7800342 TI - Lymph node metastases in gastric cancer: significance of positive number. AB - To investigate the significance of the number of node metastases in gastric cancer and its relationship to traditional anatomical classification, 305 patients who underwent a radical gastrectomy and extended lymphadenectomy (R3/4) with curative intent were reviewed. Lymph node metastases was found in 191 (62.6%) patients. The incidence of lymph node metastases was closely related to the depth of cancer invasion as well as the extent of lymph node group involvement. The frequency of metastases in different lymph node locations was related to the location of the primary tumor. The 3-year survival rates for patients with node involvement and without were 42.1 and 92.3%, respectively. In node number analysis, the distribution of the N1 group and the N4 group involvement was rather characteristic and could be predicted from a node number < 4 or > 12. The predictability of N2 and N3 involvement from node numbers 4-8 and 9-12 was less satisfactory. On the whole, patients with a metastatic node number < 4 could be considered to be N1 and had a relative good prognosis. Patients with node number 4-10 could be considered as N2 and > 10 as an incurable disease with distant metastases. Both had a poor prognosis. The data suggest that lymph node number represents the biologic behavior of cancer instead of the anatomic consideration of conventional N stage. The number of metastatic lymph node number is a good prognostic indicator with similar predicting power as the conventional node stage. PMID- 7800343 TI - Hyperthermia enhances the cytotoxicity against hypoxic cells of RP-170, a new 2 nitroimidazole nucleoside hypoxic cell sensitizer. AB - The effect of the new hypoxic cell sensitizer, 1-[2-hydroxy-1-(hydroxymethyl) ethoxy]methyl-2-nitroimidazole (RP-170), combined with heat against EMT6/KU cells, was determined under conditions of in vitro hypoxia. Heat-induced cytotoxicity for the EMT6/KU cells was increased to a greater extent under conditions of hypoxia and a normal pH of the medium. Hypoxia also reduced the surviving fraction of the cells treated either with RP-170 alone or with RP-170 plus heat. The concomitant treatment of RP-170 and heat inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia in all experimental groups, with a significant difference (p < 0.05). Therefore, RP-170 combined with exposure to heat may be an effective treatment for hypoxic cells in a solid tumor, as these cells are resistant to radiation and/or to many chemotherapeutic agents. PMID- 7800344 TI - Effect of methotrexate, doxorubicin and mitoxantrone on human peritoneal mesothelial cell function in vitro. AB - Recent studies have demonstrated that intraperitoneal instillation of dialysis solutions and drug additives may adversely affect the function of peritoneal cell populations. Therefore the aim of the present investigation was to examine the short-term effects of antineoplastic agents on human peritoneal mesothelial cells (HPMC). We have assessed the integrity of HPMC membrane and mechanisms of intracellular potassium transport. There was no evidence of significant cytotoxicity (as measured by 86Rb release) during a 60-min exposure of HPMC to either methotrexate (10(-6)-10(-4) M), doxorubicin (10(-7)-10(-5) M) or mitoxantrone (10(-7)-10(-5) M). In HPMC exposed to doxorubicin (10(-6) M) the intracellular transport of potassium, as assessed with 86Rb as its analogue, was not affected. Methotrexate (10(-5) M) diminished Na,K-ATPase activity and simultaneously enhanced the 86Rb transport via furosemide-sensitive pathway. Mitoxantrone reduced the furosemide-sensitive 86Rb influx in a dose-dependent manner and at a concentration of 10(-4) M it also impaired the ouabain-dependent 86Rb influx. These data demonstrate that antineoplastic agents interfere with HPMC function which might contribute to the oncostatic-induced peritoneal toxicity. PMID- 7800345 TI - [3H]-thymidine uptake and lipid peroxidation by tumor cells on embelin treatment: an in vitro study. AB - Using a rapid technique to assess drug-induced cell toxicity, a fibrosarcoma cell line was exposed in vitro to increasing concentrations of embelin, a benzoquinone derivative of Embelia ribes Burm., and simultaneously inoculated with [3H] thymidine. After regular time intervals, the cells were examined for incorporation of the labelled thymidine in DNA, lipid peroxide and glutathione levels. A dose-dependent decrease in labelled thymidine uptake, lipid peroxide and glutathione levels was observed on embelin administration. PMID- 7800346 TI - The effect of tumor necrosis factor alpha on a human renal cell carcinoma xenotransplanted into nude mice: comparison of intravenous and intraperitoneal injection. AB - The effect of recombinant human tumor necrosis factor alpha (TNF-alpha) on tumor growth and tumor cell proliferation of a human renal cell carcinoma transplanted into nude mice as well as on the body weight of the tumor-bearing animals has been studied. Due to differences of the effect of TNF-alpha after intravenous and intraperitoneal injection reported in the literature the influence of the two routes of application was presently studied. There was no effect on tumor growth with either route of application. Only the mode of growth showed a tendency to an increased rate of growth at the beginning of the treatment and a following increased growth deceleration. A slight change of the 3H-thymidine labeling index and the mitotic index was observed only after intraperitoneal injection of TNF alpha indicative of a more cytostatic than cytotoxic effect of the drug. This is supported by the lack of an increase of necrotic cells. Although a rather high dose of TNF-alpha was applied, no effect on the body weight of the animals, i.e. no toxic effect of the treatment, has been found. PMID- 7800347 TI - Genetic analysis of the arylamine N-acetyltransferase polymorphism in breast cancer patients. AB - The association of the arylamine N-acetyltransferase polymorphism and breast cancer has been investigated by analysis of genomic DNA from 160 breast cancer patients and 132 healthy women. Five mutations of the NAT2 gene were studied by using allele-specific PCR amplification and restriction mapping with the endonucleases FokI and Ddel. Eight allelic variants of the NAT2 gene were identified in both, patients with breast cancer and control groups, with relative frequencies. Wild-type 0.194 and 0.219, 341C+481T+803G 0.433 and 0.345, 341C+481T 0.048 and 0.076, 282T+590A 0.205 and 0.222, 282T 0.059 and 0.044, 590A 0.011 and 0.024, 803G 0.016 and 0.052, 857A 0.035 and 0.019, respectively. The prevalences for the poor acetylator genotypes were 53 and 51% for the patients with breast cancer and the control group, respectively. Seven patients with the rare lobular breast cancer showed reduced frequency for NAT2 mutations (p < 0.05) and all of them had the extensive acetylator genotype (p < 0.01). This preliminary observation suggests that extensive acetylation may be related to lobular breast cancer. No genetic support for association of the NAT2 polymorphism and other histologic types of breast cancer was found. Any differences in the acetylator rate between breast cancer patients and healthy subjects may be secondary to breast cancer itself, but not involved in the pathogenesis of the disease. PMID- 7800348 TI - Antitumor effects of intraarterial infusion of tumor necrosis factor/lipiodol emulsion on hepatic tumor in rabbits. AB - Human recombinant tumor necrosis factor (TNF) suspended in lipiodol (TNF/lipiodol emulsion) was injected via the hepatic artery, and its antitumor effects on VX2 tumor inoculated into the liver were evaluated. In TNF/lipiodol-treated rabbits, soft-X-ray study revealed an accumulation of lipiodol in the liver tumor and the TNF concentration in the tumors was significantly higher than in rabbits treated with free TNF. 7 days after the various treatments, the tumor growth ratio evaluated macroscopically was found to be significantly lower in TNF/lipiodol emulsion-treated rabbits compared to rabbits treated with either free TNF or lipiodol (p < 0.05). Microscopically, the necrotic-area ratio of the tumors in the TNF/lipiodol emulsion-treated group was also significantly greater than in any other group (p < 0.01). Pathohistologically, liver tumors treated with TNF/lipiodol emulsion revealed massive necrosis associated with occlusive thromboangitis in the tumor vessels and fibrous capsule formation around the tumor. In these rabbits, the elevation of serum transaminase after the treatment was transient and tissue damage in the surrounding noncancerous liver tissue was minimal. These findings therefore suggest that the intraarterial infusion of TNF/lipiodol emulsion may produce prominent antitumor effects, possibly due to the retention of TNF in the tumors, which causes damage to the endothelium of the tumor vessels. PMID- 7800349 TI - Management of early breast cancer: an Australian consensus report. Clinical Oncological Society of Australia, the Australian-New Zealand Breast Cancer Trials Group, the Medical Oncology Group of Australia and the Breast Section, Royal Australasian College of Surgeons. PMID- 7800351 TI - Silent sinus syndrome. PMID- 7800350 TI - A phase II trial of vindesine in hepatocellular cancer. AB - Sixteen patients with histologically confirmed inoperable hepatocellular carcinoma were treated with vindesine 3 mg/m2 i.v. weekly. Anemia, leukopenia and neuritis were documented but no severe or life-threatening toxicity was seen. There were no objective responses among the 14 evaluable patients. Eight had a no change status (median duration of 16 weeks, range 6-33), while the remaining 6 had progressive disease as their best evaluation. The median survival time was 20 weeks. Vindesine does not have a therapeutic effect in patients with advanced hepatocellular carcinoma. PMID- 7800352 TI - More on macular holes. PMID- 7800353 TI - Is smoking a risk factor for nonarteritic AION? PMID- 7800354 TI - Confusing licensure with education: medicine's slippery slope. PMID- 7800355 TI - The course of visual recovery after optic neuritis. Experience of the Optic Neuritis Treatment Trial. AB - PURPOSE: To define the time course of visual recovery after optic neuritis and factors predictive of this course in the patients enrolled in the Optic Neuritis Treatment Trial. METHODS: The cohort for this study consisted of the 438 patients who completed the 6-month follow-up visit. Visual acuity was measured at baseline and at seven follow-up visits during the first 6 months. Factors predictive of recovery were evaluated with univariate and multivariate statistical tests. RESULTS: Visual recovery was rapid in all three treatment groups. In almost all patients, regardless of treatment group and initial severity of visual loss, improvement began within the first month. Among the 278 patients with baseline visual acuity of 20/50 or worse, all patients improved at least one line of visual acuity, and all except six improved at least three lines, during the 6 month follow-up period. Baseline visual acuity was the best predictor of the 6 month visual acuity outcome (P = 0.0001). Older age was statistically associated with a slightly worse outcome (P = 0.02), but this appeared to be of no clinical importance. CONCLUSIONS: In most patients with optic neuritis, visual recovery is rapid. The only factor of value in predicting the visual outcome is initial severity of visual loss. However, even when initial loss is severe, visual recovery is still good in most patients. Patients not following the usual course of visual recovery should be considered atypical. For such patients, further investigation in regard to etiology of the visual loss may be appropriate. PMID- 7800356 TI - Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. AB - PURPOSE: To characterize visual morbidity in giant cell arteritis and to assess prognosis with respect to treatment. METHODS: Record review of 185 patients with coded diagnosis of giant cell (cranial) arteritis examined at the Bascom Palmer Eye Institute from January 1, 1980, to January 31, 1993. RESULTS: Forty-five patients with biopsy-proven giant cell arteritis had visual symptoms, and 41 individuals (63 eyes) lost vision. The visual loss was unilateral in 19 patients (46%), sequential in 15 (37%), and simultaneous in 7 (17%). Anterior ischemic optic neuropathy developed in 88% of eyes, visual acuity was 20/200 or worse in 70%, 21% had no light perception, and the majority of field defects in testable eyes, aside from central scotomas associated with loss, showed altitudinal or arcuate patterns. Six patients lost vision during corticosteroid therapy for systemic symptoms of giant cell arteritis, whereas in 39 patients visual symptoms prompted steroid treatment. For visual symptoms, 25 patients received intravenous methylprednisolone, whereas 20 received oral prednisone alone. In the 41 patients with visual loss, vision was unchanged in 20 (49%), it worsened in 7 (17%), and it improved in 14 (34%). Subsequent fellow eye involvement was observed only with oral therapy, and a greater percentage of patients (9/23 [39%] versus 5/18 [28%]) improved after intravenous treatment. CONCLUSIONS: In the authors' series, patients with visual loss due to giant cell arteritis had a 34% chance for some improvement in visual function after corticosteroid treatment. Intravenous therapy may diminish the likelihood of fellow eye involvement and was associated with a slightly better prognosis for visual improvement. PMID- 7800357 TI - Ophthalmic manifestations of vertebral artery dissection. Patients seen at the Mayo Clinic from 1976 to 1992. AB - PURPOSE: To determine the ophthalmic manifestations of vertebral artery dissections. METHODS: Fifty-one separate episodes of vertebral artery dissections evaluated at the Mayo Clinic from 1976 through 1992 were studied. In all cases, the diagnosis had been documented with angiography. RESULTS: There were 28 men and 19 women (mean and median age, 39 and 40 years, respectively; range, 8-61 years). There were ophthalmic findings in 86% of the episodes. Visual symptoms, in decreasing order of frequency, were diplopia (45% of the episodes), blurred vision (14%), transient visual dimming (8%), oscillopsia (4%), photophobia (4%), upside-down vision (2%), positional transient visual obscuration (2%), and unilateral dry eye (2%). Ophthalmic signs in decreasing order of frequency were nystagmus (37% of the episodes), ocular misalignment (cranial nerve palsy or skew) (33%), Horner syndrome (27%), decreased corneal sensation (22%), ptosis (16%), visual field defect (10%), abnormal pursuits and saccades (6%), ocular bobbing (4%), internuclear ophthalmoplegia (4%), anisocoria (4%), and pinpoint pupils (2%). CONCLUSION: Vertebral artery dissections occur in a relatively young population. Most of the patients in our study had ophthalmic manifestations at the time of diagnosis. Heightened awareness of this entity should enable the consulting ophthalmologist to have a role in the diagnosis and treatment of vertebral artery dissection. PMID- 7800358 TI - A report of 131 cases of endoscopic laser lacrimal surgery. AB - BACKGROUND: Despite the many advantages of endoscopic laser dacryocystorhinostomy, clinical data have been sparse, and the effectiveness of this procedure has not been fully evaluated. METHODS: Among 127 patients (131 procedures) who underwent endoscopic laser lacrimal surgery, 92 procedures with longer than 3 months of follow-up were evaluated. The authors used endoscopic sinus surgery equipment, radiosurgical instruments, otodrill, microrongeur, holmium:YAG and contact neodymium:YAG lasers. RESULTS: After the primary operation, 71 (77.2%) of 92 cases were symptom-free and had positive results on primary Jones dye test. With simple revision of failed cases, 88 (95.7%) of 92 cases were treated successfully. CONCLUSION: Improvement of surgical technique and use of adequate surgical instruments were essential in increasing the rate of success. Endoscopic laser surgery is useful in treating patients with lacrimal passage obstruction, but a longer period of observation is necessary to confirm its effectiveness. PMID- 7800359 TI - Herpes zoster ophthalmicus in Malawi. AB - OBJECTIVE: The objective was to describe the complications and outcomes of herpes zoster ophthalmicus in a population of young Africans with a high seroprevalence of human immunodeficiency virus type 1 in which treatment often is delayed and in which antiviral drugs are not available. METHODS: Twenty-seven patients with herpes zoster ophthalmicus presenting consecutively to a large urban hospital were examined and followed. Treatment was limited to that which was locally available. RESULTS: Visual outcomes were poor. Sixty-six percent of eyes had final visual acuity less than 20/60. Forty percent had light perception or no light perception visual acuity. Severe keratouveitis and corneal perforation were common and responsible for most poor visual outcomes. CONCLUSION: Young Africans with herpes zoster ophthalmicus are at a high risk for significant visual loss. PMID- 7800360 TI - Dapsone-induced neutropenia in patients treated for ocular cicatricial pemphigoid. AB - BACKGROUND: Dapsone is used widely in treating ocular cicatricial pemphigoid, leprosy, and dermatologic disorders. Hemolysis is a well-known complication of dapsone therapy. Rarely, neutropenia or agranulocytosis may occur, resulting in up to a 50% mortality rate. To the authors' knowledge, agranulocytosis has not been reported in patients treated with dapsone for ocular cicatricial pemphigoid. METHODS: The authors report two cases of dapsone-induced neutropenia with bone marrow suppression in patients with ocular cicatricial pemphigoid. RESULTS: Neutropenia was detected on routine laboratory examination 8 and 10 weeks after initiating dapsone therapy. Bone marrow biopsy showed acellular or hypocellular marrow. Leukocyte count returned to baseline value after cessation of dapsone. CONCLUSION: Patients with ocular cicatricial pemphigoid who were treated with dapsone are at increased risk for agranulocytosis. Dapsone-induced neutropenia may not be a dose-dependent phenomenon. The authors indicate that there is a need for routine monitoring of leukocyte counts, especially 8 to 10 weeks after initiating therapy. Signs or symptoms of infection require immediate investigation. PMID- 7800361 TI - Increased serum levels of eosinophil cationic protein and eosinophil-derived neurotoxin (protein X) in vernal keratoconjunctivitis. AB - PURPOSE: To evaluate whether the eosinophil preformed mediators, eosinophil cationic protein X, and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX) are detectable in serum and can be used as markers of eosinophilic inflammation. METHODS: A competitive radioimmunoassay was used to detect serum levels of eosinophil cationic protein and EDN/EPX in 31 patients with vernal keratoconjunctivitis (VKC) and in 15 healthy controls. RESULTS: Mean serum levels of both eosinophil cationic protein and EDN/EPX were significantly higher in patients with VKC than in controls. There was a good correlation between serum levels of eosinophil cationic protein and EDN/EPX. No significant difference in mean serum eosinophil cationic protein levels was observed between patients with positive radioallergosorbent test (RAST) results and those with negative RAST results who have VKC, whereas mean EDN/EPX and total immunoglobulin E serum levels were significantly higher in patients with positive RAST results than in those with negative RAST results who have VKC. Serum eosinophil cationic protein, but not EDN/EPX, levels were significantly related to total immunoglobulin E levels. CONCLUSION: The authors' data indicate that serum levels of eosinophil cationic protein and EDN/EPX are useful markers of eosinophilic ocular inflammation in VKC. PMID- 7800362 TI - Granular corneal dystrophy. Visual results and pattern of recurrence after lamellar or penetrating keratoplasty. AB - BACKGROUND: Granular corneal dystrophy is a rare indication for corneal transplantation. Both penetrating and lamellar keratoplasty have been recommended, but because granular corneal dystrophy is known to recur within the donor material and multiple grafts may be necessary, the best surgical option has not been clearly established. The cellular cause of the dystrophy is unknown and the authors hypothesized that the rate and pattern of recurrence within lamellar and penetrating grafts might give clues to its etiology. METHODS: The authors compared the visual outcome, rate, and pattern of recurrence after 20 penetrating keratoplasties and 11 lamellar keratoplasties for granular corneal dystrophy. RESULTS: Penetrating keratoplasty and lamellar keratoplasty have a good visual outcome in granular corneal dystrophy. Visual acuities after both procedures were not statistically different. Recurrence of the dystrophy within the graft material was almost universal within 4 years. It first appeared centrally and superficially, occasionally adopting a vortex pattern suggesting epithelial involvement. The recurrence-free interval was independent of size and type of graft performed. CONCLUSION: The authors recommend lamellar keratoplasty as a primary procedure in managing visually disabling granular corneal dystrophy if the deposits are limited to the superficial cornea. This is particularly applicable in younger patients in whom multiple procedures may be necessary over a lifetime due to recurrence of the dystrophy, and the lower morbidity rate associated with lamellar keratoplasty becomes appreciable. Although granular corneal dystrophy generally is classified as a stromal dystrophy, the pattern of recurrence is more consistent with an epithelial or tear-borne abnormality than a disease of the stromal keratocyte. PMID- 7800365 TI - Long-term results after removal of dislocated intraocular lenses from the retinal surface through a limbal approach. AB - BACKGROUND: The authors describe the use of a limbal approach for removing dislocated intraocular lenses (IOLs) from the retinal surface to minimize surgical trauma and optimize visual outcome. METHODS: Thirteen consecutive patients underwent removal of a dislocated posterior chamber IOL (PC IOL) from the retinal surface through a limbal approach. The surgical technique used in all patients included a limbal incision from the 3- to 9-o'clock positions; open-sky vitrectomy, grasping the IOL at the angle between loops and optics with an iris hook; and IOL removal through the corneoscleral opening. In all except one patient, who had high-degree myopia, an IOL was re-implanted during the same surgical procedure (free sulcus fixation of a PC IOL over remnants of the capsular bag, 7 patients; sulcus fixation of a PC IOL over remnants of the capsular bag combined with 1 transscleral suture, 3 patients; and implantation of an anterior chamber IOL, 2 patients). RESULTS: No retinal or corneal complications secondary to IOL removal and re-implantation through a limbal approach could be detected over an average follow-up period of 22.3 months (range, 17-27 months). Best-corrected visual acuity was 20/40 or better in seven patients, between 20/50 and 20/400 in three, and less than 20/400 in three. Visual outcome worse than 20/40 was related to pre-existing macular degeneration in five patients and retinitis pigmentosa in an additional one. CONCLUSIONS: The use of a limbal approach allows removal of an IOL from the retinal surface and secondary IOL implantation in the preferred site during the same surgical procedure. Because no special instrumentation is needed, this technique also is suitable for primary removal if dislocation occurs intraoperatively. The visual outcome and the long-term absence of complications recorded in our series indicate that a limbal approach may offer a reasonable alternative in managing IOLs luxated onto the retinal surface. PMID- 7800363 TI - Dynamic shifts in corneal topography after radial and transverse keratotomy. AB - PURPOSE: The authors aimed to quantitate the dynamic patterns of change in corneal topography after multistaged radial and transverse keratotomy using digitized video-keratography. METHODS: Single and paired radial and transverse keratotomies, with videokeratoscopy between each stage and at the end of the procedure, were performed on fresh animal cadaver eyes using an artificial orbit system. RESULTS: All incisions led to central flattening. A single radial keratotomy caused flattening adjacent to the incision, and steepening 180 degrees away. A paired radial keratotomy caused increased flattening in the meridian of the incisions, and less flattening 90 degrees away. A single transverse incision caused steepening adjacent to the incision and diffuse flattening elsewhere. A paired transverse incision caused flattening near the optical center along the meridian bisecting the incisions and steepening 90 degrees away. CONCLUSION: The authors have demonstrated that computerized videokeratography can be used successfully to systematically quantitate dioptric shifts in multiple hemimeridians and measurement zone diameters after refractive surgery. PMID- 7800366 TI - Cutaneous melanoma-associated retinopathy. AB - PURPOSE: To define further the syndrome of cutaneous melanoma-associated retinopathy, of which only five affected patients have been reported previously. METHODS: Three men with melanoma-associated retinopathy were examined and studied electrophysiologically. Two were studied in detail psychophysically. RESULTS: Visual symptoms consisted of flickering black and white spots, shimmering patches of colors, and night blindness. The onset was acute and nonprogressive. Reduced amplitudes were observed in the flash electroretinographic b-wave and the pattern electroretinogram. Color vision, contrast sensitivity, and light- and dark adapted perimetric sensitivities were abnormal. In one patient, the rate of dark adaptation was normal with elevated final cone and rod thresholds. CONCLUSIONS: Melanoma-associated retinopathy is a paraneoplastic syndrome distinct from cancer associated retinopathy with a different visual prognosis. It may preferentially affect men. PMID- 7800364 TI - Retained lens fragments after phacoemulsification. AB - PURPOSE: The authors present the clinical features of patients with retained lens fragments after phacoemulsification and their outcome after pars plana vitrectomy. METHODS: The authors performed a retrospective chart review of 62 patients who had surgical management of posteriorly dislocated lens fragments after phacoemulsification during the 3-year period from January 1990 to December 1992. RESULTS: Eight of the 62 patients underwent vitrectomy on the same day as the cataract surgery. Of the remaining 54 patients examined in the outpatient clinic, initial clinical features included marked intraocular inflammation (87%), elevated intraocular pressure of 30 mmHg or higher (46%), and corneal edema (46%). Retinal detachment was present before vitrectomy in one patient and occurred after vitrectomy in two others. Initial visual acuity was 20/200 or worse in 68% of patients. After vitrectomy, final visual acuity was 20/40 or better in 68% of patients. Using the percentage of patients with 20/40 or better final visual acuity, there was no statistically significant difference in surgery performed within 7 days (70%), between 1 and 4 weeks (60%), and after 4 weeks (70%). Twenty (80%) of 25 patients with initial posterior chamber intraocular lenses (PC IOLs) and 16 (62%) of 26 patients with initial anterior chamber IOLs (AC IOLs) achieved 20/40 or better visual acuity. A visual acuity outcome of 20/200 or worse occurred in all three patients with retinal detachment. Six of the eight patients who underwent vitrectomy on the same day as the cataract surgery achieved 20/30 or better visual acuity. CONCLUSIONS: The timing of vitrectomy did not influence visual acuity outcomes. Intraocular lenses inserted at the primary operation did not adversely affect the visual outcome. However, vitrectomy on the same day as cataract surgery generally yielded favorable visual acuity outcomes and eliminated the need for a second operation at a later date. In most patients with retained lens fragments, management with vitrectomy allowed good visual acuity outcomes. PMID- 7800367 TI - The detection of post-traumatic angle recession by gonioscopy in a population based glaucoma survey. AB - BACKGROUND: Blunt trauma is responsible for most eye injuries in urban populations. Anterior chamber angle recession has been reported to be the most common sign of previous blunt trauma to the eye. The cumulative lifetime prevalence of post-traumatic angle recession has not been reported previously, and the relation between angle recession and glaucoma in a population-based setting is unknown. METHODS: As part of a population-based glaucoma survey, gonioscopy was performed on 987 (82.7%) of 1194 inhabitants of the village of Mamre, near Cape Town, South Africa, who were 40 years of age or older. RESULTS: Some degree of angle recession was identified in one eye of 60 people and in both eyes of 86 people. Men were affected more than three times as often as women in the fifth, sixth, and seventh decades. The cumulative lifetime prevalence of angle recession in this community was 14.6%. The prevalence of glaucoma in people with angle recession was 5.5% (8/146). Of 87 eyes with 360 degrees of angle recession, only 7 (8.0%) had glaucoma. Excessive alcohol consumption was significantly related to the presence of angle recession in women (P < 0.001). The prevalence of monocular blindness due to trauma was 2.5% (25/987). CONCLUSION: Although the importance of the study may be limited to this community, the findings suggest that future population-based studies of ocular trauma should include gonioscopy on all individuals examined. Secondary glaucomas, especially those related to trauma, should be screened for in developing countries when trying to establish the prevalence of potential visual loss from glaucoma. PMID- 7800369 TI - Wegener's granulomatosis. PMID- 7800368 TI - The prevalence of primary open-angle glaucoma in a population-based study in The Netherlands. The Rotterdam Study. AB - PURPOSE: The objective of this study is to assess the prevalence of primary open angle glaucoma (POAG) in a defined population in Rotterdam, The Netherlands. METHODS: The Rotterdam Study is a single-center prospective cohort study of a total population of more than 10,000 people, 55 years of age or older. For the current analysis, the first 3062 consecutive, unselected, noninstitutionalized participants were examined according to standard protocols, including perimetry. The diagnosis of POAG was based on the presence of a glaucomatous visual field defect combined with either a vertical cup: disc ratio of 0.5 or more or a cup:disc ratio asymmetry of 0.2 or more, or an intraocular pressure (IOP) more than 21 mmHg, with open and normal anterior chamber angles. RESULTS: The overall prevalence of POAG in the current study was 1.10% (95% confidence interval [CI]: 1.09, 1.11). Age-specific prevalence figures increased from 0.2% (95% CI: 0.16, 0.24) in the age group of 55 to 59 years to 3.3% (95% CI: 2.57, 4.04) in the age group of 85 to 89 years. Men had a more than three times higher risk of having POAG than women (odds ratio, 3.6). In 52.9% of the patients, POAG had not been diagnosed previously. Of these patients, 38.9% had IOPs of 21 mmHg or lower. In 8.8% of the eyes (2.9% of patients), visual acuity was 20/200 or less due to POAG. CONCLUSION: The overall prevalence of POAG in the current study was 1.1%. The prevalence of POAG was higher in men than in women. Of the untreated patients, 38.9% had IOPs of 21 mmHg or lower. PMID- 7800371 TI - Incompletely erupted third molars in the line of mandibular fractures. A retrospective analysis of 57 cases. AB - A retrospective investigation was carried out of 57 cases of mandibular angle fractures, where a completely or partially impacted third molar was present in the line of fracture. Closed reduction was used in all of the cases, using intermaxillary fixation over a period of 42 days. Antibiotics were given to all patients for a period of 1 week. Thirty-one patients (55%) were treated within the first 24 hours and 43 (75%) within 48 hours. Infection at the fracture site occurred in two patients (3.5%). Both of these patients had been treated within the first 24 hours. It is concluded that closed reduction with retention of the mandibular third molar within the line of a mandibular angle fracture can be carried out with less morbidity compared with cases in which rigid fixation is used and movement of the jaws permitted immediately. Because of the size of the study group, no relationship could be demonstrated between cases with infection and the time from trauma to fixation. PMID- 7800370 TI - Temporomandibular joint pathosis related to sex, age, and dentition in autopsy material. AB - The purpose of this autopsy study was to test the hypotheses that temporomandibular joint (TMJ) arthrosis is more common in women than in men, increases with age, and is more common in edentulous persons than in those with natural teeth. Two hundred forty-eight TMJs removed at autopsy from 224 fresh cadavers were investigated macroscopically with dissection or cryosectioning. Age was found to be a significant factor in prediction of TMJ arthrosis (p < 0.001) and of disk perforation (p < 0.05). No significant association was found between morphologic changes in the TMJ and the factor of sex for the whole group. Disk displacement and disk perforation were, however, more common in the joints of women than men in the group of persons 80 years of age or older (p < 0.05). There were significant associations (p < 0.001) between arthrosis, disk displacement, disk deformation, and disk perforation. There were no statistically significant differences in the prevalence of morphologic changes in the joints from persons with 10 or more natural teeth in each jaw compared with those from persons without natural teeth. The results of this study showed that TMJ arthrosis is more frequent in older than in younger persons. TMJ disk displacement generally appears necessary for the development of perforations. The findings of this study indicate that sex and dentition are not major factors for the development of TMJ pathosis in elderly individuals. PMID- 7800372 TI - Timing of facial osteotomies. A consensus conference. AB - A concensus conference on the timing of facial osteotomies was held in Jonkoping, Sweden. Seven teams consisting of a maxillofacial surgeon and an orthodontist representing five countries discussed treatment planning for young patients with maxillomandibular deformities with special emphasis on timing. Patients with severe syndromic facial deformities were not considered. Consensus was reached that for most deformities it is best advised to wait until growth has ceased, as determined by longitudinal cephalometric data. This rule is less tight for Angle Class II than for Class III cases. For asymmetries often there is still not enough scientific evidence to obtain well-founded uniform agreement. PMID- 7800373 TI - Cyclosporin A in an adhesive base for treatment of recalcitrant oral lichen planus. An open trial. AB - Patients with symptomatic oral lichen planus often require therapy to reduce signs and symptoms of the condition. For this purpose, corticosteroids are frequently used. In this study the effect of another immunosuppressive drug, cyclosporin A was evaluated; it was applied as a topical drug four times daily and contained 0.025% cyclosporin A. The study group was composed of nine symptomatic patients in whom the diagnosis of oral lichen planus was confirmed by histopathologic examination including immunofluorescence. All patients had unsuccessfully undergone previous treatment with topical or systemic corticosteroids. The minimum follow-up period in the present study was at least 4 months. Four patients showed partial response to treatment with respect to signs and symptoms. None of the patients had a complete remission. Five patients showed no response or even complained of an increase of signs and symptoms. No adverse side effects of the drug were recorded during follow-up. Although the number of patients has been small, the results of this study indicate that topical application of cyclosporin A (0.025%) in the treatment of recalcitrant oral lichen planus does not offer a distinct advantage over the use of topical corticosteroids. PMID- 7800375 TI - Tongue necrosis as a complication of temporal arteritis. AB - Tongue necrosis is a rare complication in giant cell arteritis, an entity in which both temporal arteritis and rheumatic polymyalgia may be included as two different manifestations of the same pathologic process. The case of a 79-year old patient who had tongue necrosis 3 hours after ingestion of 2 mg of ergotamine tartrate is presented. This complication was the basis for the diagnosis of temporal arteritis. We reviewed possible clinical manifestations of temporal arteritis and cases of tongue necrosis in the world literature. The possible existence of triggering factors that seemed to be present in 11 of the published cases was analyzed. In seven of these cases ingestion of ergotamine derivates had taken place. PMID- 7800374 TI - Clinical and lymphocyte responses to beta-carotene supplementation in 11 HIV positive patients with chronic oral candidiasis. AB - Eleven HIV-positive patients with chronic oral candidiasis were supplemented with 60 to 120 mg of beta-carotene daily for 3 to 7 months. Lymphocyte profiles were evaluated at intervals to help assess immune competence. Although there was a modest increase in some lymphocyte values at 2 months, there was a significant decrease in numbers of CD4 and CD8 cells and CD4 percentage of lymphocytes after 6 months of beta-carotene supplementation. Serum triglyceride and liver enzyme levels were not affected by the beta-carotene supplementation. No improvement was observed in the control of the oral candidiasis. Under the conditions of the study, there was no indication that daily beta-carotene supplements enhanced immune competence or was of benefit in managing oral candidiasis. PMID- 7800376 TI - Hereditary gingival fibromatosis. Report of an extensive four-generation pedigree. AB - A Brazilian family with hereditary gingival fibromatosis is described with multiple affected subjects in four generations. A total of 50 (48%), of 105 at risk offspring in a family of 132 members were affected, consistent with an autosomal dominant mode of inheritance. This family appears to represent the largest pedigree with this condition reported in the literature. PMID- 7800377 TI - Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation. AB - Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant. PMID- 7800378 TI - A clinical trial of antioxidant supplements in the treatment of oral leukoplakia. AB - Seventy-nine patients with oral leukoplakia that was histologically verified as either hyperkeratosis or epithelial dysplasia with hyperkeratosis were enrolled in an antioxidant supplementation program for the treatment of the oral lesions. The patients received 30 mg of beta-carotene, 1000 mg of ascorbic acid, and 800 IU of alpha-tocopherol per day for 9 months. Clinical improvement of the oral lesion was noted in 55.7% of the patients and was more likely to occur in patients who reduced their use of alcohol or tobacco (p = 0.0056). Although risk factor reduction was important, approximately half of the patients who did not alter their exposure to either alcohol or tobacco showed clinical improvement. The antioxidant supplementation significantly increased serum and tissue levels of beta-carotene, ascorbic acid, and alpha-tocopherol, but these changes did not correlate strongly with clinical improvement. PMID- 7800379 TI - Proliferative verrucous leukoplakia. Four cases with flow cytometric analysis. AB - Proliferative verrucous leukoplakia is a slow-growing but highly aggressive precancerous form of leukoplakia of unknown cause. Proliferative verrucous leukoplakia is though to possess a continuous spectrum of clinical and histopathologic expression, ranging from simple hyperkeratosis to invasive squamous cell carcinoma. Early diagnosis is difficult because of an initial innocuous character, but multiple and rapid multifocal warty recurrences are common. This article reports four additional archival cases of proliferative verrucous leukoplakia to determine if flow cytometric analysis can be useful in the early diagnosis of proliferative verrucous leukoplakia. Flow cytometric analysis was performed on available formalin-fixed paraffin-embedded specimens (N = 27). Flow cytometric analysis results showed DNA aneuploid cell lines in each proliferative verrucous leukoplakia case studied (DNA index range, 1.1 to 2.6). In all four patients the abnormal cell line DNA index appeared to be maintained throughout the sampling period. The results suggest flow cytometric analysis could be a possible aid in early recognition of proliferative verrucous leukoplakia and might enable aggressive therapy at an earlier stage. PMID- 7800380 TI - A case of histiocytic medullary reticulosis complicated with x-ray-irradiated oral cancer. AB - We report the case of a patient in whom oral squamous cell carcinoma and a fatal reactive form of histiocytosis were simultaneously manifested. Our conclusions indicate that such a hematophagocytic syndrome may occur in the setting of oral squamous cell carcinoma as previously described in other malignancies. PMID- 7800381 TI - Pathogenesis of induced rat periapical lesions. AB - Studies of the mechanisms of pathogenesis of periapical lesions were undertaken using a rat model of surgical pulp exposure. In this model, periapical lesions develop rapidly between days 0 and 15 (active phase) and more slowly thereafter (chronic phase). A Gram-negative anaerobic flora, similar to that seen in human beings, are quickly established. Lesions contain a mixed inflammatory cell infiltrate consisting of T cells, neutrophils, B cells, macrophages, and plasma cells. Helper T cells predominate during the active phase, whereas suppressor T cells are more frequent in the chronic phase. Extracts of periapical lesions contain bone-resorbing activity, the highest levels of which are present when lesions are actively expanding. Most bone-resorbing activity is mediated by the cytokine interleukin-1 alpha, as determined by biochemical criteria and antibody neutralization studies. Prostaglandin2 accounts for 10% to 15% of resorptive activity. Cells that express interleukin-1 alpha were identified in pulp beginning on day 2 after exposure and in periapical tissue beginning on day 7, as determined by in situ hybridization and immunostaining. Macrophages, fibroblasts, neutrophils, and osteoclasts were positive for interleukin-1 alpha mRNA and protein. Cells that express tumor necrosis factor alpha were also detected, whereas cells expressing interleukin-1 beta or tumor necrosis factor beta were absent. Finally, periapical bone destruction was inhibited by 60% by treatment with interleukin-1 receptor antagonist. These studies establish a key role for interleukin-1 alpha in the pathogenesis of periapical lesions in the rat model. PMID- 7800382 TI - Mediators of acute and chronic periradicular lesions. AB - Multiple mechanisms are involved in the pathologic changes associated with formation of acute and chronic periradicular lesions. Mechanical injury to the periradicular tissues can cause activation of several pathways of inflammation and release of nonspecific mediators. Continuous irritation of periradicular tissues can cause activation of several pathways of inflammation and release of nonspecific mediators. Continuous egress of antigens from a pathologically involved root canal can also result in one or a combination of the various types of immunologic reactions. A number of these reactions participate in the destruction of periradicular tissues. Because of complex interactions between the various components of these systems, the dominance of any one pathway or substance may be difficult to establish. PMID- 7800384 TI - Color coding of radiographic changes over time by means of image addition. AB - Differences between sequential radiographs may be displayed in color if the individual radiographs are transformed into monochromatic images and then added. Information in regions where the radiographs are identical is retained whereas differences are emphasized by the color coding that comes about in a quantitative manner from the gray level values in the sequence of radiographs. By using the three additive primary colors, red, blue, and green, two or three radiographs from a sequence may be added. Every possible state of a bone disease, progression, regression, or any combination, will produce a different and specific color code. Different development cycles are described, and the color coding that appears when color image addition is performed is analyzed. The color addition technique should constitute a useful substitute or alternative to subtraction. PMID- 7800383 TI - Taxonomy, ecology, and pathogenicity of the root canal flora. AB - The bacteria present in infected root canals include a restricted group of species compared with the total flora of the oral cavity. Conditions exist in the root canal that permit the growth of anaerobic bacteria capable of fermenting amino acids and peptides, whereas bacteria that mainly obtain energy by fermenting carbohydrates are restricted by lack of available nutrients. During the course of infection interrelationships develop between microbial species and population shifts are produced as a result of these interactions. Strong associations between certain species are present. These associations are most likely based on nutritional demands and nutritional relationships. The pathogenicity of the polymicrobial root canal flora is dependent on bacterial synergy. PMID- 7800385 TI - Angiography of the temporomandibular joint. Description of an experimental technique with initial results. AB - The vascular supply to the temporomandibular joint is not completely understood. To form a base for advancement in this area we developed a method for experimental angiography of the temporomandibular joint that was applied to fresh temporomandibular joint autopsy specimens. Via the external carotid artery the vessels were infused with a mixture of barium and an acrylic resin. The specimens were sectioned and contact radiographs were obtained. These showed the vascularity of the joint and the surrounding structures with great detail. Most of the vascular supply appears to come from the lateral and medial aspects of the condyle head and from the anterior and posterior disk attachments. The method was applied to both normal and abnormal joints and the results suggest that this method could be used to gather further understanding of the vascularity of the temporomandibular joint relative to disease. PMID- 7800386 TI - Exposure parameters and their effects on diagnostic accuracy. AB - A new method for analyzing diagnostic accuracy is introduced. A diagnostic accuracy curve may be obtained by plotting receiver operating characteristic analysis data, P(A), as a function of exposure. By means of diagnostic accuracy curves the effects on diagnostic accuracy of tube potential, exposure, and size of carious lesions was studied. It was found that the effect of the tube potential on the accuracy of caries diagnosis is negligible. About 25% of the variation in diagnostic accuracy depends on the exposure and about 80% on lesion depth. With the lesion depth constant, about 75% of the variance in diagnostic accuracy depended on observer performance. The peak of a diagnostic accuracy curve indicates optimum performance. This is found at an exposure that gives a radiographic density of about 1 in enamel and dentin although the tolerable exposure increases with increased lesion depth. PMID- 7800388 TI - [Pharmacokinetic study of dibromodulcitol in children with brain tumors]. AB - Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5 patients. Cerebrospinal fluid dibromodulcitol levels were also analysed in two patients. Bromoepoxydulcitol, dianhydrodulcitol are cytotoxic, whereas bromoanhydrodulcitol, andhydroepoxydulcitol are inactive metabolites detectable during the biotransformation of dibromodulcitol. The HPLC method, developed by our team, is suitable for the determination of both dibromodulcitol and its main metabolites (dianhydrodulcitol and bromoanhydrodulcitol). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexite-derivatives in pediatric patients. With the exception of one patient, concentration-time curves were analysed by the one compartment model. From the 30th minute following administration, dibromodulcitol was detectable in all plasma samples for at least 12 hours, its concentration however was usually undetectable by the 24th hour. Though highly variable in value, dianhydrodulcitol concentrations were detectable during all but one therapeutic courses. The following peak concentrations were observed: dibromodulcitol: 3.46-30.63 microM; dianhydroldulcitol: 1.70-6.17 microM; bromoanhydrodulcitol: 0-5.63 microM. The correlation of area under the curve for bromoanhydrodulcitol and dibromodulcitol was exponential up to 200 microMxh with no additional increase detectable above this limit; the distribution of dianhydrodulcitol values were described by a maximum-curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives were detectable in the cerebrospinal fluid even if the concentration of the individual metabolite remained undetectable in plasma. The cerebrospinal fluid concentrations of dibromodulcitol were almost constant in the period from 2.5 to 8 hours following administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7800387 TI - [Experience in the management of patients with artificial heart valves (analysis of the material of the Bekes County Cardiology Clinic)]. AB - Authors report of 152 patients, 146 of whom underwent single mitral (n = 70), single aortic (n = 64), double aortimitral (n = 17) and aortic-mitral-tricuspid (n = 1) valve replacement with mechanical prostheses. 6 patients received bioprostheses. The mean age was 55 years. Follow-up ranged from 1 to 23 years (mean 5.1 years). The methodology of follow-up consisted patients examination in our office (at least twice a year) and questionnaire. Valve related complications were defined as paravalvular leak (6 cases), valve thrombosis (3 cases), thromboembolism (13 cases), anticoagulant-related hemorrhage (21 cases), infectious endocarditis (6 cases). During care 14 patients died. The most common causes of death were left-ventricle insufficiency (n = 6), infectious endocarditis (n = 3), prosthetic valve thrombosis (n = 1), cerebral hemorrhage (n = 2) and sudden death (n = 2). 138 patients (56 percent) are retired or invalid. Authors emphasize the importance of regular control and the significance of anticoagulant policy (in the target international normalized ratio to 2.5-3.5 and the provision of the antibiotic prophylaxis to avoid the late complications. PMID- 7800389 TI - [Management of childhood pseudocroup with budesonide inhalation]. AB - The authors examined 85 children who had serious recurrent pseudogroup syndrome, and re-examined them 1-3 years later. 1/3 of the patients was also allergic, mostly to mites and grasspollens. The patients got either regular, daily two inhalation, or their parents were taught to inspire the drug in the case of stenotic cough of hoarseness. Half of the patients did not answer to our letter. The parents of 43 patients answered and described their observations according to the inquiry letter. 2/3 of treated children either amolioreted definitely of became symptom free. 12 patients had 30 laryngeal attacks before the budesonide treatment whereas only 3 attacks, needing hospitalisation, occurred after the budesonide treatment. 6 patients experienced definite amelioration and two children's state worsened. Budesonide therapy seemed to be useful in the prevention and therapy of recurrent laryngitic children. Further experiences using turbo-inhaler and placebo would be important for more definite statement. Nevertheless inhalative budesonide is the first drug promising fast remission of laryngeal edema. PMID- 7800391 TI - [Rupture of extrauterine pregnancy during simultaneous intrauterine pregnancy]. AB - The authors report a case of a simultaneous extrauterine and intrauterine pregnancy which posed a problem of differential diagnosis for both the surgeon and the gynecologist. After surgical treatment of the ruptured ectopic pregnancy the patient was symptom free, and later requested the interruption of her normal intrauterine pregnancy. Diagnosis was confirmed by ultrasonographic examination. PMID- 7800390 TI - [Evaluation of syncope in medicolegal expertise]. AB - The authors summarise the clinical characteristics of the syncope and neurological signs respectively caused by basilar vertebral artery insufficiency as well as carotid sinus hypersensitivity. Several authors have seen an increased number of patients with neurological symptoms caused by ischaemia in the region of the basilar artery occurring while driving and causing a traffic accident. Carotid sinus hypersensitivity as cause of driving accidents has much less importance. In the case of the authors on a 51 years old man after turning his head to the right a sudden transient loss of consciousness without signs of convulsion developed while driving a car. The attack resulted in a serious traffic accident. Vertebrobasilar insufficiency was presumed as the cause of the signs. Despite the rare incidence of isolated syncope caused by ischaemia in the region of basilar artery, after observation of one and half a year, chiefly supported by the pathological otoneurological findings, the definitive diagnosis could be established. The recurrence of the syncope could not be excluded. An inability to drive was established. The new hungarian legal regulation of 1992, of driving ability emphasises the extraordinary hazards in the traffic posed by processes the sinus of which occur associated with sudden loss of consciousness with great probability, perhaps rarely, but at any time. PMID- 7800392 TI - [On the centenary of Theodor Billroth (1829-1894)]. PMID- 7800393 TI - [Pathography of Lorinc Szabo in his poetry]. PMID- 7800394 TI - ["Integration"--more than a slogan]. PMID- 7800395 TI - [The ideal sickroom]. PMID- 7800396 TI - [Job rotation. A short report on work organization]. PMID- 7800397 TI - ["The school is very effective..."]. PMID- 7800398 TI - [Kaspar Feuerstein: "It is important to consider various opinions". Interview by Harald Verworner]. PMID- 7800399 TI - Lateral ankle sprains, Part II: Acute and chronic treatment. PMID- 7800400 TI - An algorithmic approach to the treatment of Paget's disease of the spine. AB - An algorithmic approach to the treatment of Paget's disease of the spine is based on the authors' collective experience in managing 70 patients and a review of the literature. For patients with active disease, even if asymptomatic, cyclical treatment with etidronate is recommended until normalization of biochemical parameters is achieved. For patients with back pain and/or neurologic dysfunction, cyclical etidronate treatment in the blastic and mixed phase is advocated. Those who fail to respond to calcitonin in the lytic phase should be given the new generation of bisphosphonates and gallium nitrate. No antipagetic drug therapy is indicated for the sclerotic phase. Surgery for complications of Paget's disease should be preceded by intravenous therapy to minimize intraoperative bleeding. For cases of spinal stenosis with impending paraplegia, the new bisphosphonates, mithramycin (plicamycin), or gallium nitrate should be used. If conservative treatment fails, surgery should not be delayed. PMID- 7800401 TI - Arthroscopy language. AB - The authors have devised an "arthroscopy language" to make orthopaedic surgeons' intraoperative communication clear, comprehensive, and concise. This language specifically eliminates surgeons' "freestyle" conversation at the most crucial moments of their procedure, when concentration and the coordinated work of two surgeons are essential. The language uses current arthroscopic terminology and new words that have been adapted by the authors to describe all the basic maneuvers that are used during any arthroscopic procedure. The authors believe the language brings the necessary scientific sophistication into arthroscopic surgeons' speech in the operating theater. PMID- 7800402 TI - Comparison of intra-articular morphine and bupivacaine following knee arthroscopy. AB - A prospective study was conducted to investigate and compare the analgesic effect of morphine and bupivacaine injected intra-articularly following elective knee arthroscopy performed under general anesthesia without the use of a tourniquet. Cost-effectiveness of these agents was also evaluated. Patients in Group 1 (n = 41) received 30 cc of 0.25% bupivacaine with 1:200,000 epinephrine; while Group 2 (n = 40) received 2 mg morphine (1 mg/cc) in 28 cc normal saline (total volume 30 cc). Postoperative pain scores and the amount of supplemental analgesic agents used in a 24-hour period were recorded. Results showed that patients in Group 2 reported significantly less pain overall (P < .006) and significantly lower analgesic requirements (P < .0004) at a lower average patient cost than Group 1. We conclude that intra-articular morphine reduces postoperative pain and analgesic requirements more effectively and at a lower average patient cost than bupivacaine. PMID- 7800403 TI - Acute exertional compartment syndrome occurring after performance of the army physical fitness test. AB - Acute exertional compartment syndrome has been described as occurring after sustained maximal exertion. The case described is that of acute exertional compartment syndrome of the leg occurring in a soldier after he attempted to complete the Army physical fitness test. This condition was initially neglected; necrotic muscle and acute tubular necrosis were sequelae. Earlier intervention could have occurred if the signs and symptoms were considered by the treating health care professionals. All active duty troops are required to perform to maximum exertion. Their complaints should be considered with the same differential diagnosis as those of a highly trained athlete. PMID- 7800404 TI - Combined Monteggia and Galeazzi fractures in a child's forearm. A case report. AB - We report the occurrence of a previously undescribed combined Monteggia and Galeazzi fracture pattern of the left forearm in an 8-year-old boy. Previous reports do not address the combined injury described in this article, which consists of a left radius shaft fracture with dislocation of the distal radioulnar joint, and a left ulna shaft fracture with anterior dislocation of the radiohumeral joint. An excellent result was obtained with closed reduction. Radiographic evaluation is crucial in these disorders for both diagnosis and for treatment decisions. A review of the literature is provided with specific emphasis toward the classifications, mechanisms of injury, diagnosis, associated injuries, and treatment. PMID- 7800405 TI - A 38-year-old woman with recurrent swelling of the great toe. 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 indicated below. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 7800406 TI - Stabilization of the distal radioulnar joint after ulnar styloid nonunion using Mitek anchors. AB - Nonunion of the ulnar styloid is a relatively common injury that can often be ignored. In patients presenting with pain, compromised range of motion, and decreased grip strength, careful physical examination, and dynamic radiographic evaluation may document distal radioulnar joint instability. Mitek anchors provide a simple, effective means of triangular fibrocartilage complex reattachment, providing stabilization of the distal radioulnar joint. PMID- 7800408 TI - Characterization of the modes of action of anti-Pbs21 malaria transmission blocking immunity: ookinete to oocyst differentiation in vivo. AB - The impact of immune sera, and peripheral blood cells (PBC) from mice immunized with Plasmodium berghei ookinetes; and of purified immunoglobulin or Fab fragments from anti-Pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. Infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. PBC from ookinete-immunized mice presented with non-immune serum failed to show any transmission-blocking activity. Anti-ookinete serum, intact anti-Pbs21 monoclonal antibody 13.1 or its Fab fragments, all inhibited oocyst formation significantly. When gametocyte-infected mice or gametocytes in membrane feeds were used, inhibition did not directly correlate with antibody concentration. In membrane feeders that contained ookinetes and antibody, concentration-dependent inhibition usually occurred. The efficacy of purified 13.1 IgG was dependent upon the ookinete concentration. The ookinete plasmalemma and cytoplasm were significantly disturbed after 12 h in bloodmeals that contained antibody 13.1, but not in the isotype controls. These changes may have caused the observed failure of the ookinete to migrate as rapidly as the controls from the destructive environment of the bloodmeal. PMID- 7800407 TI - Continuous cultivation of intraerythrocytic Plasmodium falciparum in a serum-free medium with the use of a growth-promoting factor. AB - Serum-free media were used to culture Plasmodium falciparum. A commercial preparation, Daigo's GF21 developed as a growth-promoting factor for many kinds of mammalian cells, and consisting of the 55-70% ammonium sulphate fraction of adult bovine serum, insulin, transferrin, ethanolamine and sodium selenite, was found to sustain growth of the parasite when Daigo's T was employed as a basal medium. The optimal Daigo's GF21 concentration for parasite growth was between 5 and 20% (v/v), with the best results at 10%. Differential counts indicated that Daigo's GF21 is essential for schizogony. Established serum-free medium, GIT, consisting of Daigo's T basal medium and Daigo's GF21, yielded good parasite growth without any supplementation. Growth-promoting factor derived from adult bovine serum in Daigo's GF21 was shown to be crucial to parasite growth. The results presented here will not only be of practical value, but will provide important information about the developmental requirements for the parasite. PMID- 7800409 TI - Random mating in a natural population of the malaria parasite Plasmodium falciparum. AB - The genetic structure of a population of the malaria parasite Plasmodium falciparum has been examined in a village in Tanzania. Seventeen alleles of the merozoite surface protein MSP-1 and 23 of MSP-2 were detected by the polymerase chain reaction (PCR) among the blood parasites of the inhabitants. Most infections contained mixtures of genetically distinct parasite clones. PCR was then used to examine individual P. falciparum oocysts, the products of fertilization events, in wild-caught mosquitoes. Forty-five out of 71 oocysts were heterozygous for one or both genes, showing that crossing between clones was taking place frequently, following uptake of mixtures of gametocytes by the mosquitoes. The frequency of heterozygous forms showed that random mating events probably occurred within mosquito bloodmeals between gametes belonging to different parasite clones. PMID- 7800410 TI - Identification and diagnosis of Leishmania mexicana complex isolates by polymerase chain reaction. AB - Following cloning of Leishmania (L.) amazonensis kinetoplast DNA two recombinant clones were identified: one specific for L. (L.) amazonensis and the other specific for L. (L.) amazonensis and closely related isolates. DNA sequences from these clones were compared with those of other kinetoplastids and oligonucleotide primers were designed to be used in the polymerase chain reaction. A pair of these primers has been shown not only to be highly specific for L. mexicana complex isolates but can also be used to distinguish between L. (L.) mexicana and L. (L.) amazonensis isolates. These primers have been tested with water-lysed cultures, crude DNA extracts from human patients, potential host reservoirs, sandfly vectors and with cell pellets after isoenzyme characterization. The results of these tests indicate that the primers can be used specifically in the presence of excess host DNA originating from the majority of South American countries. PMID- 7800411 TI - A putative Leishmania panamensis/Leishmania braziliensis hybrid is a causative agent of human cutaneous leishmaniasis in Nicaragua. AB - As part of a survey of human leishmaniasis in Nicaragua we examined phenotypic and genotypic characteristics of 40 Leishmania isolates. We identified 3 distinct parasites associated with cutaneous disease in this area; Leishmania panamensis (40% of cases), Leishmania braziliensis (33%), and a strain which exhibits the heterozygous isoenzyme and DNA fingerprinting patterns expected of a L. panamensis/L. braziliensis hybrid (27%). There was complete correlation between the isoenzyme and DNA data for each of the putative hybrids examined. All of the 'hybrids' were obtained from foci in the northern region of the country where L. panamensis and L. braziliensis occur sympatrically. These observations provide strong evidence for sexual reproduction in New World Leishmania populations and suggest that it is of taxonomic and epidemiological significance. PMID- 7800412 TI - Observations on the effects of different chemotherapy strategies on the transmission of Schistosoma mansoni in Machakos District, Kenya, measured by long term snail sampling and cercariometry. AB - Transmission of Schistosoma mansoni was monitored by routine snail sampling for Biomphalaria pfeifferi and by supplementary cercariometric measurements in 4 neighbouring study areas in Machakos District, Kenya. After 1 year, extensive, population-based chemotherapy with a single dose of praziquantel was given in 3 areas, but only minimal treatment in the fourth. In the year preceding treatment, seasonal transmission of S. mansoni and other non-human trematodes occurred in all 4 areas, despite some ecological differences and the effects of earlier treatment campaigns in 1 of the study areas. After treatment of all infected subjects in one area in which there had been earlier chemotherapy campaigns, S. mansoni transmission remained very low. It was reduced for at least 2 years after chemotherapy targeted at either all heavily infected subjects or all infected school children, but it was unaffected in an area where treatment was restricted to those few very heavily infected cases at risk of developing disease. Nowhere was transmission entirely eliminated by chemotherapy and that of non-human trematodes continued unabated. The snail data correspond well with the human, parasitological data. Targeting school children was as effective as more extensive campaigns, but chemotherapy alone never stopped S. mansoni transmission: reinfection was inevitable, at rates determined by ecological factors affecting snail populations. PMID- 7800413 TI - Platyhelminth FMRFamide-related peptides (FaRPs) contract Schistosoma mansoni (Trematoda: Digenea) muscle fibres in vitro. AB - Molluscan FMRFamide and two recently discovered platyhelminth FMRFamide-related peptides (FaRPs), GNFFRFamide from the cestode Moniezia expansa and RYIRFamide from the terrestrial turbellarian Artioposthia triangulata, cause dose-dependent contractions of individual muscle fibres from Schistosoma mansoni in vitro. The most potent FaRP tested was the turbellarian peptide RYIRFamide, which produced a concentration-dependent effect between 10(-9) and 10(-7) M. FMRFamide and GNFFRFamide were less potent, inducing contractions between 10(-8)-10(-6) M and 10(-7)-10(-5) M respectively. The contractile effect of each of these peptides was blocked by the presence of 1 microM FMR-D-Famide. FMRF free acid did not elicit contraction of the muscle fibres. The FaRP-induced contractions did not occur if the Ca2+ was omitted and 0.5 microM EGTA was added to the extracellular medium. The FaRP-induced contractions were not blocked by the Ca2+ channel blockers nicardipine, verapamil or diltiazem, although high K+-induced contractions of these fibres were blocked by nicardipine. These data indicate the presence of FaRP receptors on schistosome muscle fibres and demonstrate their ability to mediate muscle contraction. The action of these endogenous flatworm peptides on schistosome muscle is the first demonstration of a direct excitatory effect of any putative neurotransmitter on the muscle of a flatworm, and establishes a role for FaRPs in neuromuscular transmission in trematodes. In addition, it provides the first evidence that the peptidergic nervous system is a rational target for chemotherapeutic attack in parasitic platyhelmiths. PMID- 7800414 TI - Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni. AB - The tegument of the human parasite Schistosoma mansoni is critical for parasite survival within the mammalian host. The role of protein kinase C (PKC), a major effector molecule in the phosphoinositide pathway, in maintaining the structural organization of this syncytial layer was examined in adult worms. Phorbol 12 myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB), phorbol esters that activate PKC, induced formation of surface vesicles as determined by light and scanning electron microscopy. Similar results were seen with sn-2-dioctanoyl glycerol, a synthetic analogue of diacylglycerol. No effect was seen in parasites incubated with 4-alpha-phorbol ester or alpha isomers of PMA or PDB, compounds that do not activate PKC. Vesicle formation was reversible in parasites treated with sn-2-dioctanoyl-glycerol but not with phorbol esters. The tegument of male worms was more sensitive to the effect of phorbol esters than females. Transmission electron microscopy revealed vacuolization of the tegument. These data suggest that signal transduction pathways may have a critical role in the maintenance of the structural integrity of the tegument of parasitic helminths. PMID- 7800415 TI - Altered behaviour of carbohydrate-bound molecules and lipids in areas of the tegument of adult Schistosoma mansoni worms damaged by praziquantel. AB - By using fluorescent probes the distribution and fluid properties of lipid and saccharide-bound molecules was assessed in the tegument of praziquantel (-) treated Schistosoma mansoni adult male worms. Our results show that higher amounts of glycoproteins and/or glycolipids are exposed in damaged areas of the membrane compared with undamaged ones. At damaged regions these molecules present high lateral diffusion coefficient and mobile fraction values which suggests that after praziquantel(-) treatment they are being shed by the worm into the medium. The lateral diffusion coefficient of the lipid analogue 5'-octadecanoyl aminofluorescein is unchanged in damaged or undamaged areas but the mobile fraction is significantly reduced at damaged areas. The immunological significance of these altered surface properties is discussed. PMID- 7800416 TI - Schistosomicidal activities of Lymnaea stagnalis haemocytes: the role of oxygen radicals. AB - Macrophage-like defence cells (haemocytes) of the pond snail Lymnaea stagnalis mediate cytotoxicity through reactive oxygen intermediates (ROIs). This activity is NADPH-oxidase dependent, as in mammalian phagocytes during the respiratory burst. In this study, mother sporocysts of schistosomes, the compatible Trichobilharzia ocellata and the incompatible Schistosoma mansoni evoke in vitro ROI activities (detected by luminol dependent chemiluminescence, LDCL) from L. stagnalis haemocytes. S. mansoni is encapsulated by haemocytes and eliminated, whereas T. ocellata escapes encapsulation and survives. Both schistosomes were equally susceptible to in vitro oxidative damage from exposure to hydrogen peroxide and to ROIs generated by a xanthine/xanthine oxidase system. Protocatechuic acid, a specific antagonist of NADPH-oxidase, delayed the killing of T. ocellata and S. mansoni sporocysts by haemocytes of resistant snails (Biomphalaria glabrata and L. stagnalis, respectively). We conclude that ROIs take part in haemocyte-mediated cytotoxicity. However, neither a snail's capability to generate ROIs, nor a schistosome's susceptibility to ROIs, determine snail/schistosome incompatibility. Snail/schistosome compatibility is rather determined by the parasite's ability to modulate haemocyte behaviour such that effective encapsulation and the generation of lethal concentrations of ROIs are prevented. PMID- 7800417 TI - Schistosoma mansoni host-parasite relationship: interaction of contrapsin with adult worms. AB - Contrapsin, a serine protease inhibitor (serpin) present in mouse serum, was compared with that found in adult Schistosoma mansoni worm homogenates, which although immunologically identical to contrapsin in mouse serum, had a higher molecular weight in Western blotting. Immunolocalization studies demonstrated parasite-associated contrapsin on the surface and interstitial cells of adult male worms. After extraction of these parasites with Triton X-114, contrapsin was found in the aqueous phase of the detergent, suggesting it is unlikely to be an integral membrane protein. Treatment of adult worms with deoxycholate resulted in a change in the electrophoretic behaviour of worm-derived contrapsin. Parallel studies with trypsin suggested this was due to interaction of the serpin with a protease. Using porcine pancreatic trypsin as a model for a putative schistosome protease reacting with contrapsin, we have shown that trypsin, following complex formation with contrapsin, loses immunogenicity. Thus, when contrapsin-trypsin complexes were used as immunogen, the resulting antisera contained antibodies to contrapsin and contrapsin-trypsin complexes only, and none to native trypsin. Thus, epitopes characterizing native trypsin were presumably either masked following complex formation with contrapsin, or their processing and presentation to antigen presenting cells was suppressed, so that an antibody response was not mounted against them. These observations encourage speculation that S. mansoni may be elaborating an immune evasion strategy whereby immunologically sensitive proteases are first complexed with host serpins, which would render them immunogenically inert, and then cleared from the circulation by the host's reticulo-endothelial system. In this way the immune system would be unable to 'see' sensitive parasite proteases sufficiently to mount a response against the parasite. PMID- 7800418 TI - Trypanosoma (Nannomonas) godfreyi sp. nov. from tsetse flies in The Gambia: biological and biochemical characterization. AB - We provide evidence from isoenzyme analysis, hybridization with repetitive DNA probes, behavioural studies and morphometrics that 4 trypanosome isolates from Glossina morsitans submorsitans in The Gambia constitute a new species now named Trypanosoma (Nannomonas) godfreyi. The bloodstream trypomastigotes of T. (N.) godfreyi are relatively small with a mean length of 13.7 microns (range: 9.1-21.8 microns) and a mean width of 1.65 microns (range: 0.65-2.69 microns). There is no free flagellum and the marginal kinetoplast is subterminal to a rounded posterior end; the undulating membrane is usually conspicuous. As with other Nannomonas, T. godfreyi developed in the midgut and proboscis of Glossina and infections matured in 21-28 days in laboratory G.m. morsitans. In The Gambia the normal vertebrate host appears to be the warthog, Phacochoerus aethiopicus, although elsewhere other wild and domestic suids may also be implicated in the life-cycle. T. godfreyi was identified unequivocally using a 380 bp DNA probe specific for a major genomic repeat sequence; its isoenzyme profile distinguished it clearly from T. simiae and three strain groups of T. congolense: savannah, riverine forest and kilifi. PMID- 7800422 TI - Urinary tract infections in children. PMID- 7800419 TI - A genetic analysis of reproduction in Strongyloides ratti. AB - Strongyloides ratti has a complex life-cycle with two adult generations, one free living and dioecious and one parasitic and female only. The parasitic females reproduce by parthenogenesis, but it is unclear whether this is mitotic or meiotic in nature. This question has been addressed genetically by analysing the progeny of parasitic females that were heterozygous at an actin locus for evidence of allelic segregation. Such progeny were similarly heterozygous showing that segregation had not occurred. It was therefore concluded that reproduction in the parasitic female of S. ratti is functionally mitotic. PMID- 7800421 TI - Is screening urinalysis worthwhile in asymptomatic pediatric patients? PMID- 7800420 TI - Characterization of a major surface-associated excretory-secretory antigen of Trichinella spiralis larvae with antibodies to keyhole limpet haemocyanin. AB - A multi-subunit antigen (native M(r) > 200 kDa, reduced M(r) 97-100 kDa) has been identified in homogenates of Trichinella spiralis larvae using affinity-purified rabbit anti-keyhole limpet haemocyanin (KLH) antibodies and its cross-reactivity with KLH was confirmed by competition blotting. The antigen was not present at the larval surface but was exposed after treatment of the larvae with the detergent cetyltrimethyl ammonium bromide (CTAB) which removed the surface coat. This correlated with a significant decrease in insertion of the surface restricted fluorescent lipid probe AF18, indicating that the surface coat must be lipidic in nature. Unlike KLH, the larval antigen blotted onto nitrocellulose was itself periodate insensitive. Periodate treatment of whole larvae, however, resulted in shedding of the surface, to which anti-KLH antibodies then bound intensely. Anti-KLH antibodies also recognized three (49, 55, 108 kDa) of the four most dominant antigens in excretory-secretory (ES) products of cultured larvae, whose excretion-secretion was increased with CTAB. The nature, location and function of the antigen is discussed. PMID- 7800423 TI - Hematuria in children. AB - A work-up of a child with suspected hematuria should be undertaken once the primary physician has determined that there actually are red blood cells in the urine and that the hematuria is persistent. Evaluation of a child with persistent microscopic hematuria is facilitated with the determination of whether the blood originates from the glomeruli or whether it comes from elsewhere in the urinary tract. Clues to a glomerular origin include the presence of other manifestations of glomerular disease such as significant proteinuria, RBC casts, and dysmorphic erythrocytes in the urinary sediment, hypertension, and renal insufficiency. Clues to the blood originating from the lower urinary tract include blood clots in the urine, normal erythrocyte morphology, and a pertinent history pointing to the lower tract such as that of trauma, urolithiasis, urological or vascular abnormality, or symptoms of bladder inflammation. The initial evaluation should include a detailed patient history and family history as well as a careful physical examination looking for clues to the presence of a familial, hereditary, or chronic kidney disease. A logical, stepwise initial work-up should follow with the goal of ruling out life-threatening and treatable diseases. If there are no indications for immediate further intervention and the cause of the hematuria remains unclear after the initial work-up has been completed, the parents and patient should be reassured that there are no life-threatening conditions and that although the etiology of the blood in the urine is yet unknown, there is time to follow the patient and plan for additional studies if and when they are indicated. The family's concerns (ie, "Is this cancer?," "Will my child require dialysis and transplantation?") should be addressed frankly, and the physician should mention those diagnoses that may lead to renal failure, but have not been absolutely ruled out yet before a kidney biopsy has been performed, such as Alport's syndrome and IgA nephropathy. The child with isolated microhematuria should be evaluated regularly with urinalyses looking for persistence of the hematuria and appearance of proteinuria, blood pressure measurements, and renal function tests. If the microhematuria persists for 6 to 12 months, a kidney biopsy should be considered.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7800424 TI - The evaluation of the child with proteinuria. PMID- 7800425 TI - Nephrotic syndrome in children. PMID- 7800426 TI - Hemolytic uremic syndrome: the most common cause of acute renal failure in childhood. PMID- 7800427 TI - Inhibitory effects of theophylline, terbutaline, and hydrocortisone on leukotriene B4 and C4 generation by human leukocytes in vitro. AB - Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) are considered to be important mediators in the pathophysiology of asthma. Theophylline, terbutaline, and hydrocortisone are drugs commonly used in the treatment of asthma. In the present study we have investigated the in vitro inhibitory effects of theophylline, terbutaline, and hydrocortisone on LTB4 and LTC4 generation from human leukocytes. After preincubation in the presence of these drugs, the cells were stimulated with the calcium ionophore A 23187 and the supernatants were analyzed for their LTB4 and LTC4 content using reverse-phase high-performance liquid chromatography (HPLC). Total leukotriene (LT) production (the combined amounts of LTB4 and LTC4) was dose-dependently inhibited by pretreatment with theophylline, terbutaline or hydrocortisone. Therapeutic levels of hydrocortisone (5 x 10(-6) M) plus theophylline (5 x 10(-5) M) inhibited LTB4 and LTC4 production in an additive way, as did the combination of hydrocortisone plus terbutaline (5 x 10( 8) M). A statistically significant effect of diminished LTB4 generation was obtained after preincubation with therapeutic levels of theophylline plus terbutaline, but no such effect was seen for LTC4 levels. The in vitro inhibitory effects on LTB4 and LTC4 generation from human leukocytes by theophylline, terbutaline, and hydrocortisone, as well as the additive effect of hydrocortisone plus theophylline or terbutaline, add to our understanding of the therapeutic effects of these drugs in the treatment of bronchopulmonary obstruction. PMID- 7800428 TI - Legionella and Pneumocystis pneumonias in asthmatic children on high doses of systemic steroids. AB - Asthma is increasingly treated as an inflammatory disease with inhaled and/or systemic corticosteroids. We report 3 cases of unusual pneumonias associated with high doses of oral steroids. Two patients contracted Legionella pneumonia and one patient contracted Pneumocystis carinii pneumonia. With increasing usage, it is important for physicians to be aware of the possible infectious complications of high dose steroids. This report highlights the risk of corticosteroid treatment in asthma in predisposing to opportunistic infections that have not heretofore been readily associated with asthma. PMID- 7800430 TI - Forced expiratory maneuvers in children aged 3 to 5 years. AB - There is no consensus about reproducibility and reliability of spirometry in young children. We evaluated forced expiratory maneuvers from 98 children aged 3 to 5 years with a variety of respiratory disorders before and after bronchodilator treatment. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were analyzed for reproducibility by the American Thoracic Society criteria and for reliability based on the coefficient of variation (CV%). Over 90% of the patients cooperated, however, while 95% could exhale for at least 1 second, very few generated an FEV1 on all 6 "best" efforts. This clearly improved with age. Of all patients nearly 60% performed reproducible pre- and postbronchodilator sets of FVC but only 32% performed reproducible sets of FEV1. Based on the CV%, those patients who could reproducibly perform an FVC and FEV1 did it quite reliably (mean CV%, 9.38 and 7.01 for FVC and FEV1, respectively). We conclude that while some very young children can perform spirometry, reliability of performance cannot be assumed in this age group. PMID- 7800429 TI - The effect of transfusion on pulmonary function in patients with thalassemia major. AB - Pulmonary involvement has been documented in thalassemia major (TM). We studied 12 patients with TM before and 24 hr after transfusion to evaluate the effect of transfusion on baseline lung function. Personal and family histories of respiratory illnesses were obtained by a questionnaire. Spirometry and carbon monoxide diffusion capacity (KCO) measurements were made. Blood gases (PO2 and SO2) were determined on arterialized samples. Baseline expiratory volumes and flows were within normal range in all patients. Transfusion resulted in a significant reduction of forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25 and 75% vital capacity (FEF25-75%). In two subgroups of patients identified by the questionnaire, those with no history of airway disease had normal baseline flows and no posttransfusion changes; those with history of airway obstruction had lower pretransfusion flows and significantly decreased posttransfusion FEV1 and FEF25-75%. The mean pretransfusion KCO value of 80% predicted for the whole group, significantly increased after transfusion (P < 0.05). Blood gases also significantly increased after transfusion (P < 0.05). When tested for the spirometric response to albuterol, patients with a history of asthma had a slightly greater increase in FEV1 and FEF25-75% than those who had never had asthma. We conclude that in our small study group, transfusion resulted in improved gas exchange and lung perfusion. The effect on flow limitation evident in some patients could, in part, be related to a preexisting bronchial hyperreactivity. Accurate evaluation of pulmonary function and of bronchial reactivity is advisable for patients with TM. PMID- 7800431 TI - Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis. AB - By improving pulmonary function in patients with cystic fibrosis (CF), recombinant human deoxyribonuclease (rhDNase) may affect resting energy expenditure (REE). To examine this hypothesis, we measured REE by indirect calorimetry in seven patients with CF before (day 0) and 2 weeks after (day 15) administration of aerosolized rhDNase. Baseline REE was higher in all patients than predicted for age, sex, and weight (mean +/- SEM 128 +/- 4.9%; range, 116 147%). After 2 weeks of aerosolized rhDNase, mean forced vital capacity (FVC) (in % of predicted values) improved significantly from 54.1 +/- 2.2 to 66.3 +/- 4.2% (mean improvement, 12.3%; 95% CI, 2.8, 21; P < 0.05) and REE decreased by 11.0% (95% CI 3.2, 17.5; P < 0.05). In addition, the larger the improvement in FVC in response to rhDNase the greater the decrease in energy expenditure (r - 0.88). The REE decreased in all patients who had an increase in FVC and remained unchanged in two patients who had no change in FVC. We conclude that patients with CF whose lung function improve in response to aerosolized rhDNase have an acute and proportionate reduction in their resting energy expenditure. PMID- 7800432 TI - Ventilation-perfusion relationships in preterm infants after surfactant treatment. AB - Arterial-alveolar partial pressure differences for oxygen, carbon dioxide, and nitrogen were measured before and after surfactant replacement therapy on 15 occasions in 14 ventilator-dependent preterm infants with hyaline membrane disease (HMD). Eight treatments resulted in a significant improvement in arterial partial pressure of oxygen (PaO2) 2 hr after treatment; 7 did not. Neither group showed any significant change in arterial-alveolar partial pressure differences for oxygen, nitrogen, and carbon dioxide. This observation suggests that if surfactant replacement therapy produces an improvement in PaO2 it does so by recruitment of atelectatic alveoli with a balanced ventilation/perfusion ratio rather than by redistribution of ventilation within already ventilated alveoli. PMID- 7800433 TI - The Hering-Breuer deflationary reflex in the newborn infant. AB - Initial observations on healthy term infants using the forced partial expiratory flow-volume technique with an inflatable jacket suggested that this technique was stimulating the Hering-Breuer deflationary reflex, a reflex which has not been systematically studied in man. To investigate this fully, esophageal pressure, jacket pressure, flow and volume at the mouth were recorded during the forced partial expiratory flow-volume maneuver on 10 infants (mean age, 3.1 days; birth weight, 3533 g; gestation, 39.8 weeks). A total of 186 measurements were performed at different points in the respiratory cycle. In 159 (85%) recordings inspiratory effort was evident with a fall in esophageal pressure within 166 msec; in some cases this occurred before the jacket was fully inflated. This was associated with a reduction of 23.4 cm H2O in mean intrathoracic pressure, which was 2.5 times that occurring during normal tidal breathing. In the remaining 27 measurements a plateau pressure was associated with closure of the upper airway. When the squeeze was applied at low lung volumes (end-expiration) the inspiratory effort occurred significantly earlier (133 msec) and stronger (reducing peak intrathoracic pressure to 15.8 cm H2O) than when applied at end-inspiration (181 msec with a reduction in intrathoracic pressure to 25.2 cm H2O). The observed inspiratory response was highly consistent, representing the deflationary reflex as described by Hering and Breuer in 1868. The stronger and more rapid onset of inspiration at low lung volume supports the claim made by Breuer that it has a protective role on functional residual capacity (FRC) in young infants. PMID- 7800434 TI - Frequency distribution of breath sounds as an indicator of bronchoconstriction during histamine challenge test in asthmatic children. AB - In order to study changes in respiratory sounds associated with acute bronchoconstriction and -dilatation, breath sounds of 11 children with asthma (age range, 10-14 years) were recorded at the chest and at the trachea during histamine challenge test and after subsequent bronchodilatation. The changes in frequency spectra of breath sounds were compared with simultaneous changes in forced expiratory volume in 1 second (FEV1). In seven children who responded to histamine with a decrease in FEV1 of more than 15%, there was a significant relationship between percentage change in FEV1 (delta FEV1) and percentage change in median frequency (delta F50) of expiratory breath sounds recorded at the chest (r = 0.865; beta = -0.706, P = 0.0001) and at the trachea (r = 0.888; beta = 1.12, P = 0.0001). The association between breath sound intensity and FEV1 was weaker. Based on ANOVA, the increase of F50 during the challenge test was significantly larger in children who responded to histamine than in those who were non-responsive (P = 0.0016). At the chest, a decrease of 15% in FEV1 corresponded to an increase of 8% in expiratory F50. The provocative dose of histamine inducing a decrease of 15% in FEV1 (PD15FEV1) and the provocative dose causing an increase of 8% in F50 (PD8F50) were significantly related (r = 0.927, P = 0.003). We conclude that spectral analysis of breath sounds can be used to indicate airway obstruction during bronchial challenge tests in children, and may be adapted for tests in pre-school children. The results suggest that the same mechanisms that induce airflow limitation due to inhaled histamine may generate an increase in frequency content of breath sounds in children with asthma. PMID- 7800435 TI - A new device for ambulatory cough recording. AB - Nocturnal cough reporting on diary cards has been shown to be unreliable and inconsistent. Whether subjective reporting of daytime cough is equally unreliable remains unknown. We have, therefore, developed a new and easily portable device (RBC-7) that records electromyographic (EMG) and audio cough signals for at least a 24-hr period, with a capacity of over 48 hr. Additional information is obtained from electrocardiographic (ECG) signals, and from an accelerometer indicating the level of the subject's activity. The RBC-7 can be set up with the aid of a notebook computer at the subjects home, school or workplace. Initial studies utilizing a prototype device were performed to determine the optimal position of the EMG leads and the microphone. The optimal position for the EMG leads was determined as the positive electrode in the sixth intercostal space (ICS) in the midclavicular line on the left, the negative electrode in the same position on the right, and the reference electrode in the midline over the abdomen. This position was shown to give the highest EMG voltages and the greatest difference in voltages between cough and other signals. The optimal microphone position for signal strength and comfort was over the first ICS, either right or left, close to the sternum. Recordings were performed simultaneously in 20 subjects with conventional tape recorders and the multiparametric cough monitoring system (RBC 7). Conventional tape recordings limited the duration of the studies due to the inherent restrictions. No significant difference in the number of single coughs recorded by each system was detected (correlation coefficient = 0.996). The RBC-7 offers a unique opportunity to obtain objective information on cough in ambulatory subjects over at least a 24-hr period, and to relate cough to time, activity and heart rate, while normal activities are pursued. PMID- 7800436 TI - Diaphragmatic paralysis in children: a review of 11 cases. AB - We reviewed 11 pediatric cases of diaphragmatic paralysis related to nonspinal cord injury which were managed in our Intensive Care Unit over the past 10 years. Three cases were secondary to birth trauma, 7 followed surgical procedures for congenital heart disease, and 1 occurred in association with injuries sustained in a motor vehicle accident. The paralysis was bilateral in 8 children. The diagnosis was initially suspected on clinical grounds because of respiratory distress, impossibility of weaning from the ventilator, and paradoxical abdominal respiratory movements. Confirmatory investigations included chest radiography, which revealed elevation of the affected hemidiaphragm, fluoroscopy and ultrasound, both of which demonstrated diminished diaphragmatic movement. Electromyography exhibited a failure of diaphragmatic response to phrenic nerve stimulation in 8 patients. All patients were mechanically ventilated; tracheostomy was required in 5 patients. Physiotherapy was considered a beneficial adjuvant measure. Diaphragmatic plication was attempted without success in 3 children. Seven children recovered without sequelae: Partial respiratory autonomy was achieved after an average of 2.6 months, complete autonomy after an average of 5.4 months. Two patients developed chronic lung disease; one of them remains unresponsive, and one child died following accidental extubation. We conclude that the diagnosis of diaphragmatic paralysis is predominantly clinical, and that the outcome of patients treated by adequate endotracheal mechanical ventilation is usually favorable. PMID- 7800437 TI - Role of MRI in the evaluation of ambiguous genitalia. AB - Diagnostic accuracy of magnetic resonance imaging (MRI) interpretation was assessed prospectively in patients with ambiguous genitalia or intersex problems. MRI depiction of the uterus was possible in 93%, the vagina in 95%, the penis in 100%, the testis in 88%, and the ovary in 74% of patients. The strength of MRI lies in the multiplanar capability and tissue characterization by means of T1- and T2-weighted sequences. MRI contributes to accurate morphologic evaluation of mullerian duct structures, the gonads, and the development of the phallus, all of which are essential for appropriate gender assignment and planning of surgical reconstruction. PMID- 7800438 TI - Wilms' tumor arising in a multicystic kidney. AB - We describe a child with Wilms' tumor (WT) which occurred in an unequivocal multicystic dysplastic kidney (MDK). We indicate a current nonsurgical approach to MDK, but stress the probable malignant degeneration of blastemal cells, the need to search carefully for the WT in the MDK, and the necessity on 3-monthly follow-up US studies. PMID- 7800439 TI - Emergence of mature teratoma following treatment of sacrococcygeal endodermal sinus tumor: CT and MR imaging with pathological correlation. AB - We report a case of pseudoretroconversion in which, clinically and pathologically, it appeared that an endodermal sinus tumor retroconverted to mature teratoma. An 8-month-old white female infant with a sacrococcygeal tumor, diagnosed by biopsy as endodermal sinus tumor (yolk sac tumor), was treated with chemotherapy. The residual tumor after treatment was mature teratoma confirmed by imaging and by pathological examination. We present the computerized tomography (CT) and magnetic resonance imaging (MRI) findings with pathological correlation. PMID- 7800441 TI - Sonographic evaluation of traumatic spinal cord lesions in the newborn infant. AB - We present a case of spinal cord injury due to birth trauma and assess the value of sonography for diagnosis, lesion characterization, and follow-up. Sonography is a non-invasive and easily reproducible imaging method for examining a ventilated child, and its initial sensitivity is comparable to that of MRI. Sonography is the method of choice for guiding diagnosis in this type of traumatic lesion to the newborn. PMID- 7800440 TI - Ultrasound diagnosis of birth-related spinal cord trauma: neonatal diagnosis and follow-up and correlation with MRI. AB - Two neonates, one with complete and one with incomplete birth-related transection of the cervico-thoracic spinal cord, form the basis of this report. Ultrasound and MRI findings in primary diagnosis and follow-up are described. The aim of this contribution is to bring this serious birth complication to the attention of the reader, to present the obstetrical risk factors, to describe the clinical presentation of the newborns and to make suggestions to expand the field of indications for spinal sonography. The value of spinal ultrasound in the first six months of life is stressed, especially in comparison to MRI. For definitive assessment of the lesion (transectional or nontransectional) follow-up ultrasound studies for several weeks are required. PMID- 7800442 TI - Non-union of pediatric fibula fractures: easy to overlook, painful to ignore. AB - Fracture non-union in the pediatric population may span the age range from childhood to adolescence. Fracture non-union in children and adolescents is often due to an underlying cause such as affliction with neurofibromatosis or osteogenesis imperfecta. Although less commonly seen, non-union may occur in the otherwise healthy pediatric population. We report three cases of fracture non union of the distal end of the fibula in the pediatric age group. All three were characterized by persistent local pain and tenderness following injury with radiographic evidence of fracture non-union. All three had undergone conservative treatment with extended periods of immobilization. Following surgery, all three had marked improvement of their local symptomatology. One patient's course was complicated by reflex sympathetic dystrophy syndrome. In two patients, resection of the un-united fragment at the distal fibula resulted in marked relief from pain without any increase in ankle instability. We postulate that the fracture non-union resulted in a fibrotic reaction that was so extensive that ankle stability was maintained even after removal of the fracture fragment. PMID- 7800443 TI - Fractures of the acromion in young children and a description of a variant in acromial ossification which may mimic a fracture. AB - We report on six children, from 2 to 19 months old, with a defect across the root of the acromion (basiacromion) diagnosed as a fracture in four and as an anatomical variant (separate ossification center for the lateral half of the basiacromion) in the other two. PMID- 7800444 TI - Cystic angiomatosis of bone: MR findings. AB - Cystic angiomatosis of bone is a rare disorder characterized by widespread lytic bone lesions with or without associated soft tissue or visceral lymphangiomatosis. The disorder is often initially incorrectly diagnosed as Langerhans cell histiocytosis. Unfortunately, biopsy of long bone lesions will often yield only fluid, thereby making a histologic diagnosis difficult. This report describes the MR findings in a patient with cystic angiomatosis of bone. We believe that the MR findings are highly suggestive of the correct diagnosis and that MR should eliminate the need for excisional biopsy in future cases. PMID- 7800445 TI - MRI findings of lipoma arborescens of the knee in a child: case report. AB - Lipoma arborescens is an intraarticular lesion characterized by a frond-like mass of mature fat cells, usually involving the suprapatellar bursa. It is a rare lesion in adults and extremely rare in children. Because of the fatty nature of the lesion, the MRI findings of lipoma arborescens are specific. We present the MRI findings of lipoma arborescens of the knee in a 9-year-old girl. PMID- 7800446 TI - Radiographic abnormalities in Laron dwarfism. AB - Radiographic abnormalities in two children with Laron dwarfism are described. In addition to a characteristic bone age, which was retarded for the chronological age but advanced for the height of the patients, there were marked skull changes and minor skeletal abnormalities in the long bones and vertebrae. Such findings on a skeletal survey should lead the radiologist to suspect the disorder. PMID- 7800447 TI - Cavitary pulmonary lesions in type IV Ehlers-Danlos syndrome. AB - Type IV Ehlers-Danlos syndrome (EDS) is characterized by large vessel bleeding, visceral rupture and early death. Pulmonary complications are uncommon. We report an 18-year-old patient with EDS type IV who developed recurrent large, thick walled lung cavitary lesions, probably a manifestation of focal lung rupture. Such hemorrhagic cavities are probably the basis of the bullous disease and recurrent pneumothoraces occasionally observed in type IV EDS. PMID- 7800448 TI - The Chediak-Higashi syndrome: CT and MR findings. AB - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder postulated to result from lack of regulation of fusion of the primary lysosomes. In this report we present the MR and CT features of the brain in a patient with known CHS. These findings include diffuse atrophy of the brain with diffuse periventricular decreased density identified with CT, as well as increased signal on the T2-weighted images and lack of enhancement on the T1-weighted images in the periventricular and corona radiata regions. PMID- 7800449 TI - The echogenic thalamus in hypoxic ischaemic encephalopathy. AB - This paper reports 16 term infants in whom an echogenic thalamus was identified on cranial ultrasonography. Fourteen of the patients suffered severe birth asphyxia. The prognostic significance of this finding and the underlying pathogenesis is assessed. PMID- 7800450 TI - Sturge-Weber syndrome associated with a large left hemispheric arteriovenous malformation. AB - A patient with the characteristic changes of Sturge-Weber syndrome on the right side was found to have a large arteriovenous malformation on the left side which involved the superior ophthalmic vein. This association, although previously reported, is extremely rare. PMID- 7800452 TI - Inflammatory myofibroblastic tumor of the spleen: report of a case in an adolescent. AB - Inflammatory myofibroblastic tumor (IMT) is an uncommon quasineoplastic process occurring in young patients. Splenic involvement is uncommon and occurs predominantly in older, adult patients. We present the youngest patient reported to date with splenic inflammatory myofibroblastic tumor and discuss the clinical, pathological and imaging features of this lesion. PMID- 7800453 TI - Calcifications in untreated primary duodenal lymphoma: an exceptional entity. AB - Calcifications in lymphoma are rare findings prior to therapy. We report our experience with a 13-year-old boy who presented with a primary calcified duodenal Burkitt's lymphoma. US and CT findings are described. Two differential diagnoses are discussed. PMID- 7800451 TI - Recognition of malposition of the liver and spleen: CT, MRI, nuclear scan and fluoroscopic imaging. AB - Thirteen children initially suspected to have an intrathoracic or intraabdominal mass had malposition of the liver and/or spleen discovered by ultrasound. This group consisted of five children with diaphragmatic eventration or hernia and eight with wandering spleen or liver. Careful ultrasonographic examinations were diagnostic in all patients; seven had surgical confirmation. CT, MRI, nuclear scan and fluoroscopic imaging were useful in select instances. The liver and spleen have a characteristic anatomic configuration and sonographic appearance that should enable them to be recognized, and pathological alterations appreciated, even when these organs are ectopic in location or malformed.